0.05). However, there was a significant correlation
between general stress scores and years of job experience (P = 0.05) and number
of patients treated daily (P = 0.03). The most common methods for coping with
stress were resting (71.0%), sports (45.2%) and entertainment (43.0%). Most
dentists felt that stress management courses could help to reduce stress (89.7%).
CONCLUSION: General dentists in Kerman were subject to many sources of stress in
their workplaces, with significant relationships between stress scores and years
of work experience and number of patients treated daily. Dentists should be
encouraged to participate in stress management courses to help alleviate stress.
PMID- 27606116
TI - Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose
Propofol-Fentanyl for an Awake Craniotomy.
AB - An awake craniotomy is a continuously evolving technique used for the resection
of brain tumours from the eloquent cortex. We report a 29-year-old male patient
who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month
history of headaches and convulsions due to a space-occupying brain lesion in
close proximity with the left motor cortex. An awake craniotomy was conducted
using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low
dose of propofolfentanyl. The patient remained comfortable throughout the
procedure and the intraoperative neuropsychological tests, brain mapping and
tumour resection were successful. This case report suggests that dexmedetomidine
in combination with titrated ultra-low-dose propofolfentanyl are effective
options during an awake craniotomy, ensuring optimum sedation, minimal
disinhibition and a rapid recovery. To the best of the authors' knowledge, this
is the first awake craniotomy conducted successfully in Oman.
PMID- 27606117
TI - Treatment of Aluminium Phosphide Poisoning with a Combination of Intravenous
Glucagon, Digoxin and Antioxidant Agents.
AB - Aluminium phosphide (AlP) is used to protect stored grains from rodents. It
produces phosphine gas (PH3), a mitochondrial poison thought to cause toxicity by
blocking the cytochrome c oxidase enzyme and inhibiting oxidative
phosphorylation, which results in cell death. AlP poisoning has a high mortality
rate among humans due to the rapid onset of cardiogenic shock and metabolic
acidosis, despite aggressive treatment. We report a 21-year-old male who was
referred to the Afzalipour Hospital, Kerman, Iran, in 2015 after having
intentionally ingested a 3 g AlP tablet. He was successfully treated with
crystalloid fluids, vasopressors, sodium bicarbonate, digoxin, glucagon and
antioxidant agents and was discharged from the hospital six days after admission
in good clinical condition. For the treatment of AlP poisoning, the combination
of glucagon and digoxin with antioxidant agents should be considered. However,
evaluation of further cases is necessary to optimise treatment protocols.
PMID- 27606118
TI - Variation in the Obturator Vasculature During Routine Anatomy Dissection of a
Cadaver.
AB - The obturator artery normally originates from the internal iliac artery while the
obturator vein drains into the internal iliac vein. During a routine gross
anatomy dissection class for undergraduate students at the All India Institute of
Medical Sciences, New Delhi, India, in 2016, a rare unilateral variation in the
obturator vasculature was found in a female cadaver of approximately 55 years of
age. In this case, the left obturator artery originated from the superior gluteal
artery and the left obturator vein drained into the external iliac vein.
Knowledge of such variations is necessary during hernia procedures, ligation of
the internal iliac artery and muscle graft surgeries.
PMID- 27606119
TI - A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the
Treatment of Multivessel Coronary Artery Disease.
AB - Optimal management of multivessel coronary artery disease can be complex. We
report a 67-year-old male patient who was admitted to the Padua University
Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction.
Coronary angiography showed diffuse multiple sub-occlusive lesions of the
proximal and distal left coronary vessels involving a long segment of the vessel.
On intravascular ultrasonography (IVUS), the left main artery was moderately
diseased with critically stenotic and calcified branch ostia. A successful
percutaneous coronary intervention using the T-stenting and small protrusion
technique with two drug-eluting stents (DES) was performed on the left main
artery and its main branches. Two bioresorbable vascular scaffolds were also
deployed in overlap at the mid to distal segments of the left anterior descending
artery and overlapping a previous DES at the proximal segment. The full expansion
and apposition of the struts and scaffolds to the vessel wall without residual
stenosis was confirmed by IVUS.
PMID- 27606120
TI - Suprasellar Clear Cell Meningioma in an Infant.
AB - Clear cell meningiomas are an uncommon subtype of meningioma rarely seen in
infancy. We report a case of clear cell meningioma in an 8-month-old male infant.
He presented at the Lagos University Teaching Hospital, Lagos, Nigeria, in 2015
with persistent vomiting, poor feeding and failure to thrive over a four month
period. Generalised hypertonia and hyperreflexia were noted on examination.
Computed tomography of the brain revealed a huge largely isodense suprasellar
mass with a hypodense core. The tumour, which measured 6 * 5 * 4 cm, enhanced non
uniformly with contrast injection and extended to occlude the third ventricle.
The patient underwent a bifrontal craniotomy with subtotal tumour excision. Six
hours postoperatively, he went into cardiac arrest and could not be resuscitated.
A histological diagnosis of clear cell meningioma was made as the tumour cells
were immunoreactive to epithelial membrane antigen, S100 protein and vimentin.
This case of clear cell meningioma was unusual due to its early occurrence and
supratentorial location.
PMID- 27606121
TI - Disease-Modifying Drug Possibly Linked to Placental Insufficiency: Severe
placental complications in a pregnant woman with multiple sclerosis.
AB - Disease-modifying drugs (DMDs) such as interferon (IFN)-beta and glatiramer
acetate are often prescribed to slow disability progression in patients with
multiple sclerosis (MS). However, adverse pregnancy outcomes have been reported
with these medications. We report the rare occurrence of severe placental
complications in a 30-year-old pregnant woman with MS who continued to take IFN
beta during her first trimester. She presented at the Tawam Hospital, Al Ain,
United Arab Emirates, in 2013 with early-onset fetal growth restriction. At 30
gestational weeks, she developed severe pre-eclampsia. The baby was delivered via
emergency Caesarean section and was discharged at the age of two months.
Continuation of IFN-beta during pregnancy may have contributed to the development
of placental insufficiency in this patient. Increased education regarding the
risks of DMDs for pregnant patients with MS is very important to ensure
successful pregnancy outcomes.
PMID- 27606122
TI - Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney
Transplant Rejection with Eculizumab.
AB - Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant
survival and remains a challenge in the field of organ transplantation. We report
the first use of the anticomplement agent eculizumab in Oman in the treatment of
a 61-year-old female patient with ABMR following a living unrelated kidney
transplant. The patient was admitted to the Sultan Qaboos University Hospital in
Muscat, Oman, in 2013 on the eighth day post-transplantation with serum
creatinine (Cr) levels of 400 umol/L which continued to rise, necessitating
haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No
improvement was observed following standard ABMR treatment and she continued to
require dialysis. Five doses of eculizumab were administered over six weeks with
a subsequent dramatic improvement in renal function. The patient became dialysis
free with serum Cr levels of 119 umol/L within four months. This case report
indicates that eculizumab is a promising agent in the treatment of ABMR.
PMID- 27606123
TI - Seizures as an Atypical Feature of Beal's Syndrome.
AB - Congenital contractural arachnodactyly, commonly known as Beal's syndrome, is an
extremely rare genetic disorder caused by mutations in the fibrillin-2 (FBN2)
gene located on chromosome 5q23. It is an autosomal dominant inherited connective
tissue disorder characterised by a Marfan-like body habitus, contractures,
abnormally shaped ears and kyphoscoliosis. We report a seven-year-old Omani male
who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2014
with seizures. He was noted to have certain distinctive facial features and
musculoskeletal manifestations; he was subsequently diagnosed with Beal's
syndrome. Sequencing of the FBN2 gene revealed that the patient had a novel
mutation which was also present in his mother; however, she had only a few facial
features indicative of Beal's syndrome and no systemic involvement apart from a
history of childhood seizures. To the best of the authors' knowledge, this is the
first report of Beal's syndrome with seizure symptoms as a potential feature.
PMID- 27606124
TI - Duodenum Inversum: Findings from an upper gastrointestinal series.
PMID- 27606125
TI - Coral-Red Fluorescence of Erythrasma Plaque.
PMID- 27606126
TI - Lichen Planus Pigmentosus with Blaschkoid Distribution.
PMID- 27606127
TI - 'Papaya Seed' Appearance of Subependymal Nodules on Magnetic Resonance Imaging in
a Patient with Tuberous Sclerosis.
PMID- 27606128
TI - Use of prophylactic inferior vena cava filters in trauma.
AB - [This retracts the article on p. e82 in vol. 16, PMID: 26909219.].
PMID- 27606129
TI - Erratum Notice of Author Sequence Change: Spousal concordance of diabetes
mellitus among women in Ajman, United Arab Emirates.
AB - [This corrects the article on p. e197 in vol. 16, PMID: 27226911.].
PMID- 27606131
TI - Health and Roma People in Turkey.
AB - BACKGROUND: The research and published literature on Roma health in Turkey is
much more limited than in other European countries. Among these, there are hardly
any published literature focusing on the health status, health indicators and
health behaviors. AIMS: The aim of this research is to describe the perceptions
of health-related concepts and access and the use of health services and social
determinants of the health of Roma people in Turkey. STUDY DESIGN: Descriptive
qualitative survey. METHODS: The participants were chosen by random sampling. The
semi-structured interview topic guide was developed from sources such as advice
from the Romani community leaders, published evidence and personal experience
from previous work with Roma communities. Non-directive open-ended questions
allowed the exploration of their health status, how they conceptualize health and
disease, their level of awareness on the impact of social determinants of health,
on their health status and the access and use of health services. The data
analysis was based on grounded theory. Analysis proceeded in four steps: 1.
Reading and examining the transcripts separately using open coding, 2. Extracting
the key words and codes from the transcripts and sorting them into categories, 3.
Re-reading the transcripts by using selective coding, and 4. Examining the
categories derived from the open coding systematically and determining the
concepts summarizing the material. RESULTS: The survey results are compatible
with the existing literature on Roma health and reveal that 1) there is a tight
link between the lack of social determinants of health and the poor health status
of Roma people 2) socioeconomic factors and cultural norms of the ethnic minority
are suspicious factors 3) comparative and systematic research is needed to
illuminate the actual health gaps and causal factors for them. CONCLUSION: The
research proves that the need for comparative and systematic research in Turkey
to determine the actual health status of Roma people and develop policies to
combat the health disparities is profound.
PMID- 27606130
TI - miR-23a/b regulates the balance between osteoblast and adipocyte differentiation
in bone marrow mesenchymal stem cells.
AB - Age-related osteoporosis is associated with the reduced capacity of bone marrow
mesenchymal stem cells (BMSCs) to differentiate into osteoblasts instead of
adipocytes. However, the molecular mechanisms that decide the fate of BMSCs
remain unclear. In our study, microRNA-23a, and microRNA-23b (miR-23a/b) were
found to be markedly downregulated in BMSCs of aged mice and humans. The
overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas
the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane
protein 64 (Tmem64), which has expression levels inversely related to those of
miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b
during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has
a critical role in the regulation of mesenchymal lineage differentiation through
the suppression of Tmem64.
PMID- 27606132
TI - A Comparison of Sexual Function, Psychological Status, and Sociodemographic
Characteristics of Turkish Men within Polygamous and Monogamous Marriages.
AB - BACKGROUND: A limited number of studies within the literature have entailed
objective evaluations of psychological, sexual, and emotional features of women
within polygamous marriages. However, there is a lack of studies reporting these
features among polygamous and monogamous men. AIMS: The aim of this study was to
investigate sociodemographic characteristics, sexual function, and psychological
status of polygamously and monogamously married men. STUDY DESIGN: Cross
sectional study. METHODS: The study sample comprised two groups: 35 polygamous
and 45 monogamous men in Kahramanmaras Province, Turkey. Door-to-door surveys
covered sociodemographic factors and adopted Beck Depression Inventory (BDI), and
International Index of Erectile Function - Erectile Function Domain (IIEF-EFD)
scales. RESULTS: Polygamous men showed considerably higher IIEF-EFD scores
(p<0.05). While the median score of IIEF-EFD was 25.0 for polygamous men, it was
22.0 for monogamous men. A comparison of the two groups revealed that polygamous
men had lower BDI scores. However, the difference between the groups was
statistically non-significant (p>0.05). Odds ratios and 95% confidence intervals
of monogamous men for erectile dysfunction and depression were 14.4 (95% CI: 3.1
67.5) and 7.4 (95% CI: 0.9-61.9), respectively. The main reasons for multiple
marriages reported by polygamous men, in descending order, were: 1) decreased
satisfaction of sexual desires by a wife (37.1%); 2) falling in love with the
second wife (22.8%); and 3) incompatibility with the first wife (17.1%). However,
62.9% of them responded negatively to the question: "Would you recommend
polygamous marriage to other men?" CONCLUSION: Our results showed that polygamous
men had higher erectile function and lower depression scores than monogamous men.
Further studies investigating the effects of polygamy on men's psychosexual
function are warranted. Additionally, studies that address the perspectives of
offspring and women's expectations within polygamous marriages should be
conducted.
PMID- 27606133
TI - Investigation of Behcet's Disease and Recurrent Aphthous Stomatitis Frequency:
The Highest Prevalence in Turkey.
AB - BACKGROUND: The Recurrent Aphthous Stomatitis (RAS) is the most frequently
observed painful pathology of the oral mucosa in the society. It appears mostly
in idiopathic form; however, it may also be related with systemic diseases like
Behcet's Disease (BD). AIMS: Determining the prevalence of RAS and BD in the
Northern Anatolian Region, which is one of the important routes on the Antique
Silk Road. STUDY DESIGN: Cross-sectional study. METHODS: Overall, 85 separate
exemplification groups were formed to reflect the population density, and the
demographic data of the region they represent. In the first stage, the
individuals, who were selected in random order, were invited to a Family
Physician Unit at a certain date and time. The dermatological examinations of the
volunteering individuals were performed by only 3 dermatology specialists. In the
second stage, those individuals who had symptoms of BD were invited to our
hospital, and the Pathergy Test and eye examinations were performed. RESULTS: The
annual prevalence of RAS was determined as 10.84%. The annual prevalence was
determined to be higher in women than in men (p=0.000). It was observed that the
prevalence was at the peak level in the 3(rd) decade, and then decreased
proportionally in the following decades (p=0.000). It was also observed that the
aphtha recurrence decreased in the following decades (p=0.048). The Behcet's
prevalence was found to be 0.60%. The prevalence in women was found to be higher
than in men (0.86% female, 0.14% male; p=0.022). CONCLUSION: While the RAS
prevalence ratio was at an average value when compared with the other societies;
the BD prevalence was found as the highest ratio in the world according to the
literature.
PMID- 27606134
TI - Use of Game Console for Rehabilitation of Parkinson's Disease.
AB - BACKGROUND: Parkinson's disease (PD) predisposes to falls due to postural
instability and decreased coordination. Postural and coordination exercises could
ameliorate the incoordination and decrease falls. AIMS: In this study, we
explored the efficiency of a game console as an adjunct to an exercise program in
treating incoordination in patients with PD. STUDY DESIGN: Case-control study.
METHODS: In this single-blind, prospective clinical trial, rehabilitation with
the Xbox (Microsoft; Washington, USA) game console was used as an adjunct to a
standard rehabilitation program. Thirty-three patients with PD at stages 1-3 were
enrolled in the study. All patients received the three-times weekly exercise
program and electrotherapy to back and hip extensors for 5 weeks. Study patients
played catch the ball and obstacle games on the Xbox in addition to the standard
exercise program. Patients were evaluated based on the scores from the Timed Up
and-Go Test, the Berg Balance Scale (BBS), and the Unified Parkinson's Disease
Rating Scale-II (UPDRS-II). Post-treatment scores were compared between groups.
RESULTS: Thirty-three patients were enrolled in the study (15 in the game-console
group, and 18 controls). Patients in both groups had improvements in all scores.
The end-of-treatment scores were significantly better in the study group compared
to the control group in all parameters: UPDRS (10+/-5 versus 16+/-6, p=0.002),
BBS (53+/-4 versus 47+/-8, p=0.004), and TUG (11+/-4 seconds versus 20+/-8
seconds, p<0.001). CONCLUSION: Game-exercise with a game-console was noted to be
a significant adjunct to the rehabilitation program in patients with PD in this
study.
PMID- 27606135
TI - Treatment of Orbital Complications Following Acute Rhinosinusitis in Children.
AB - BACKGROUND: The orbital complications account for about 80% of all complications
secondary to acute rhinosinusitis. If the treatment is not correct and in time,
orbital complications could progress rapidly, leading to optic neuritis,
cavernous sinus thrombophlebitis or life-threatening intracranial complications.
AIMS: To evaluate the therapeutic efficacy of conservative therapy for the
patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on
patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in
children. STUDY DESIGN: Retrospective cross-sectional study. METHODS: The
retrospective study included 31 pediatric patients with orbital complications
secondary to acute rhinosinusitis. In all cases, intensive treatment was
initiated with a combination of oral or intravenous antibiotics, glucocorticoid
and gelomyrtol forte after admission. ESS was performed if an improvement in the
condition of patients did not occur after 48 hours. However, the patients with
orbital SPA, motility disorders of eyeball or decreased vision received ESS
immediately within 24 hours. RESULTS: Sixteen patients were cured by conservative
therapy and 15 patients by ESS. All of the signs and symptoms disappeared after
conservative therapy or ESS. There were no recurrences within the follow-up
period of 1 to 8 years. CONCLUSION: Conservative therapy is an effective method
for patients with inflammatory edema and most cases of orbital cellulitis in
children. SPA can be cured by ESS.
PMID- 27606136
TI - KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer.
AB - BACKGROUND: Lung cancer is one of the most lethal cancers. It is mainly
classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung
cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The
Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6%
of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have
several similar features but their clinical course is different. AIMS: We
investigated the KRAS mutation status in SCLC and EPSCC. STUDY DESIGN: Mutation
research. METHODS: Thirty-seven SCLC and 15 EPSCC patients were included in the
study. The pathological diagnoses were confirmed by a second pathologist. KRAS
analysis was performed in our medical genetic department. DNA isolation was
performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen;
Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen;
Hilden, Germany) was used for KRAS analyses. RESULTS: Thirty-four (91.9%) of the
SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female.
SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation
was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R
(CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS
mutant and wild type patients were compared in the SCLC group, no difference was
found for overall survival (p=0.6). CONCLUSION: In previous studies, the
incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study.
Therefore, there may be ethnic and geographical differences in the KRAS mutations
of SCLC. As a result, KRAS mutation should not be excluded in SCLC.
PMID- 27606137
TI - The Effect of a Training Program on Oral Health and Behavior Change in Asthma
Patients.
AB - BACKGROUND: Asthma is a chronic disease which is prevalent throughout the world.
Physical problems such as deterioration in oral health, which may occur due to
the triggering factors of asthma as well as the ineffective use of asthma
medicine, seem to affect the daily lives of asthma patients. Therefore, it is
important to protect oral health and promote positive behavior changes in asthma
patients in order to achieve effective treatment and asthma control. AIMS: The
present study aimed to determine the effects of a training program provided for
asthma patients on oral health, inhaler use skills, and behavior change. STUDY
DESIGN: Controlled experimental study. METHODS: A total of 124 asthma patients
were included in the study. Of the patients, 62 were assigned to the experimental
group and the other 62 were assigned to the control group. Data were collected
using the patient identification form, the oral assessment guide, the inhaler use
skill form, and the evaluation form for behavior change over time. The
experimental group received training provided by the researchers on the first
meeting and one month later. Written and visual training material were used. Both
groups were subject to a final evaluation which was conducted 4 months after
their first meeting. RESULTS: It was determined that the oral assessment guide
scores (p<0.01) and inhaler use skills of the experimental group improved
significantly after the training compared to the control group (p<0.01). In
addition, it was observed that the number of patients in the experimental group
who quit smoking (p<0.05), used their medicine (p<0.01) and brushed their teeth
on a regular basis (p<0.01), and washed their mouth after inhaler use
significantly increased in the experimental group after training compared to the
control group (p<0.01). CONCLUSION: The study demonstrated that the training
provided for asthma patients improved oral health and promoted inhaler use skills
and was partially effective in promoting positive asthma-related behavior change.
PMID- 27606138
TI - Changes in Employment Status after Myocardial Infarction among Men.
AB - BACKGROUND: According to the Turkey Burden of Disease Study, 10% of the national
burden of disease is attributed to cardiovascular diseases. Although the
standardized coronary heart disease (CHD) rate is falling in general, CHD
prevalence among young people is rising. On the other hand, as a result of
increased life expectancy and higher retirement ages, the CHD rate among workers
is also increasing. Therefore, work ability and return to work after diagnosis
are important for population health and well-being. Socioeconomic factors and
working conditions may play a key role as well as clinical conditions described
in the literature that affect returning to work. AIMS: The aims of this
qualitative study are exploring the changes in employment and working conditions
of the patients after acute myocardial infarction (AMI) and affecting factors
such as socioeconomic, personal and environmental. STUDY DESIGN: Qualitative
research. METHODS: The research population are fifty-three patients who are
engaged in paid employment when the people have been diagnosed with myocardial
infarction for the first time between 2011 and 2012 at a university hospital
coronary care unit. We intended to reach the whole population. Twenty-seven
patients were contacted whose phone numbers were accessible from the hospital
records. Semi-structured in-depth interviews were conducted with twelve patients
in a meeting room at the hospital. The interviews were tape-recorded accompanied
by note-taking and the content analysis method were evaluated. RESULTS: While
many of the participants continued to work at the same job by working less, one
third of them said that they were thinking about getting an easier job if they
have the opportunity. On the other hand, in most cases, there were neither
assessments about their work ability, nor changes to their working conditions
after AMI. They had to cope with their conditions, such as economic or
psychosocial, without any support. CONCLUSIONS: While the patients have to return
to work for economic and social reasons, they expressed uncertainty about working
after a diagnosis of AMI and could not reach professional support to assess their
work abilities. Therefore, specific algorithms and assessment tools to manage the
return to work of AMI patients would be useful.
PMID- 27606139
TI - Respiratory Systems of Dental Technicians Negatively Affected during 5 Years of
Follow-Up.
AB - BACKGROUND: Dental laboratory technician is one of the professions in which dust
exposure is frequently experienced and therefore the health of workers has to be
monitored. AIMS: In this study, changes in the pulmonary functions and of
pneumoconiosis frequencies among dental technicians after five years were
investigated by comparing the results of two screenings carried out in 2008 and
2013. STUDY DESIGN: Cohort study. METHODS: In 2008 and 2013, Provincial Health
Directorate carried out two different health screenings covering all of the
dental technicians working in dental laboratories in Denizli. In both screenings,
a questionnaire was applied, with which socio-demographic and workplace
properties of the technicians were obtained. In addition, Pulmonary function
tests (PFT) and standard chest X-rays of the technicians were performed. The
results of these two screenings were evaluated by a chest specialist, and
physical examinations were performed as necessary. In 2013, technicians who had
pathologies underwent computerized tomography (HRCT). In this study, the study
group was composed of dental laboratory technicians that participated in both
screenings (2008 and 2013) and the data obtained from the screenings were
compared. The gathered data were analyzed using paired student-t and X(2) tests.
RESULTS: A total of 125 dental laboratory technicians participated in the two
screenings. Overall, 92% of the technicians were male and the mean age of the
participants was 35. Technicians were working for 9 hours a day, 6 days a week.
Total exposure time was calculated to be around 41 thousand hours. Approximately
60% of workers were smokers. When the results of PFT were analyzed, 73% of the
first evaluations were found to be normal; however, this ratio decreased to 51%
in the second analysis five years later. In the second PFT measurement, compared
to the first, there was a 23% decrease in the forced vital capacity (FVC) value,
and a 15.7% decrease in forced expiratory volume in one second (FEV1). While
restrictive disorder was found 25% in the first PFT evaluations, this ratio
increased to 31% in the second PFT. When the radiological results were
considered, 62% of the first X-ray results were found to be normal but this ratio
decreased to 18% in 2013. While reticular/reticulonodular opacities were found in
11% of cases in 2008, it increased to 30% in 2013. Seven technicians were
diagnosed with pneumoconiosis (5.6%). CONCLUSION: Respiratory tracts of the
technicians were negatively affected during the five year period. The number of
pneumoconiosis cases (5.6%) shows that it is necessary to adopt comprehensive
work health and safety precautions for laboratories.
PMID- 27606140
TI - Prosthetic Mesh Repair for Incarcerated Inguinal Hernia.
AB - BACKGROUND: Incarcerated inguinal hernia is a commonly encountered urgent
surgical condition, and tension-free repair is a well-established method for the
treatment of non-complicated cases. However, due to the risk of prosthetic
material-related infections, the use of mesh in the repair of strangulated or
incarcerated hernia has often been subject to debate. Recent studies have
demonstrated that biomaterials represent suitable materials for performing urgent
hernia repair. Certain studies recommend mesh repair only for cases where no
bowel resection is required; other studies, however, recommend mesh repair for
patients requiring bowel resection as well. AIM: The aim of this study was to
compare the outcomes of different surgical techniques performed for strangulated
hernia, and to evaluate the effect of mesh use on postoperative complications.
STUDY DESIGN: Retrospective cross-sectional study. METHODS: This retrospective
study was performed with 151 patients who had been admitted to our hospital's
emergency department to undergo surgery for a diagnosis of incarcerated inguinal
hernia. The patients were divided into two groups based on the applied surgical
technique. Group 1 consisted of 112 patients treated with mesh-based repair
techniques, while Group 2 consisted of 39 patients treated with tissue repair
techniques. Patients in Group 1 were further divided into two sub-groups: one
consisting of patients undergoing bowel resection (Group 3), and the other
consisting of patients not undergoing bowel resection (Group 4). RESULTS: In
Group 1, it was observed that eight (7.14%) of the patients had wound infections,
while two (1.78%) had hematomas, four (3.57%) had seromas, and one (0.89%) had
relapse. In Group 2, one (2.56%) of the patients had a wound infection, while
three (7.69%) had hematomas, one (2.56%) had seroma, and none had relapses. There
were no statistically significant differences between the two groups with respect
to wound infection, seroma, hematoma, or relapse (p>0.05). In Group 3, it was
observed that one (6.7%) of the patients had wound infections, while one (6.7%)
had a hematoma, one patient (6.7%) had seroma, and none had relapses. In Group 4,
seven (7.2%) of the patients had wound infections, while one (1%) had a hematoma,
three (3%) had seromas, and one (1%) had a relapse. There were no significant
differences between the two groups with respect to wound infection, seroma,
hematoma, or relapse (p>0.05). CONCLUSION: In urgent groin hernia repair
surgeries, polypropylene mesh can be safely used even in the patients undergoing
bowel resection.
PMID- 27606141
TI - Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in
Carbohydrate Residues.
AB - BACKGROUND: Investigate alterations in the expression and localization of
carbohydrate units in rat retinal cells exposed to cisplatin toxicity. AIMS: The
aim of the study was to evaluate putative protective effects of selenium on
retinal cells subjected to cisplatin. STUDY DESIGN: Animal experiment. METHODS:
Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2.
Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of
each rat was enucleated. RESULTS: Histochemically, retinal cells of control
groups reacted with alpha-2,3-bound sialic acid-specific Maackia amurensis lectin
(MAA) strongly, while cisplatin reduced the staining intensity for MAA. However,
selenium administration alleviated the reducing effect of cisplatin on the
binding sites for MAA in retinal cells. The staining intensity for N
acetylgalactosamine (GalNAc residues) specific Griffonia simplicifolia-1 (GSL-1)
was relatively slight in control animals and cisplatin reduced this slight
staining for GSL-1 further. Selenium administration mitigated the reducing effect
of cisplatin on the binding sites for GSL-1. A diffuse staining for N
acetylglucosamine (GlcNAc) specific wheat germ agglutinin (WGA) was observed
throughout the retina of the control animals. In particular, cells localized in
the inner plexiform and photoreceptor layers are reacted strongly with WGA.
Compared to the control animals, binding sites for WGA in the retina of rats
given cisplatin were remarkably decreased. However, the retinal cells of rats
given selenium reacted strongly with WGA. CONCLUSION: Cisplatin reduces alpha-2,3
bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However,
selenium alleviates the reducing effect of cisplatin on carbohydrate residues in
retinal cells.
PMID- 27606142
TI - Effect of Pregnancy on Vocal Cord Histology: An Animal Experiment.
AB - BACKGROUND: Voice may be affected during the period of pregnancy, especially in
the third trimester. However, the exact mechanisms leading to the phonatory
changes have not yet uncovered. AIMS: The aim of this study is to investigate the
possible histological changes in the vocal cords of the pregnant rats in three
separate trimesters. STUDY DESIGN: Animal experiment. METHODS: Twenty-five Wistar
Albino female rats were divided into four groups: control group, pregnancy day 7
(Group 1), pregnancy day 14 (Group 2) and pregnancy day 20 (Group 3). The
laryngeal specimens were obtained under general anesthesia. Histological
assessment was performed using Hematoxylin-eosin and toluidine blue. A
stereological analysis of vocal cord tissue was performed using a NIS-Elements
D32 Imaging Software. RESULTS: Lamina propria was observed to be edematous, and
the lamina propria area was thickened starting from the second trimester.
Glycosaminoglycans were observed to increase in the second trimester. Although
none was encountered in the control, mast cells were observed in the lamina
propria layer of the vocal cord starting in the muscular layer in the first
trimester proceed to the subepithelial region as degranulated just before term.
The covering epithelium remained unchanged throughout pregnancy. CONCLUSION:
Lamina propria thickening may be attributed to both edema and increased
glycosaminoglycans. The presence of mast cells in the cordal tissue may induce
edema during pregnancy in rats.
PMID- 27606143
TI - Comparative Relaxant Effects of Ataciguat and Zaprinast on Sheep Sphincter of
Oddi.
AB - BACKGROUND: Relaxing the sphincter of Oddi (SO) is an important process during
endoscopic retrograde cholangiopancreatography (ERCP) procedures. This issue
suggests that the easier the sphincterotomy and cannulation, the more post-ERCP
complications decrease. AIMS: To compare the relaxant effects of ataciguat (a
novel soluble guanylyl cyclase activator) and zaprinast (an inhibitor of
phosphodiesterase 5) on sheep SO in vitro, thus testing whether they can be used
during ERCP. STUDY DESIGN: Animal experimentation. METHODS: Sheep SO rings were
placed in tissue baths and their isometric tension to ataciguat and zaprinast
were tested. We also tested their isometric tension against ataciguat in the
presence of 1H-(1,2,4) oxadiazole (4,3-a) quinoxalin-1-one (ODQ) which is a
soluble guanylyl cyclase inhibitor. RESULTS: Ataciguat and zaprinast both
triggered concentration addicted relaxation on sheep SO rings (p=0.0018, p=0.0025
respectively) but the relaxation of the ataciguat was significantly greater than
that of zaprinast at all concentrations (p=0.0024). It was observed that
decreased relaxation responses were initiated by ataciguat in the presence of ODQ
(p=0.0012). CONCLUSION: Ataciguat and zaprinast both have relaxing effects on
sphincter of Oddi, although that of zaprinast is lower. We believe that ataciguat
and zaprinast can be used in ERCP procedures in order to relax the sphincter of
Oddi and thus can be used locally in order to decrease complications.
PMID- 27606144
TI - Sequential Evaluation of Pancreato-Biliary Findings in a Case with IgG4
Associated Cholangiopathy and Autoimmune Pancreatitis during Corticosteroid
Treatment.
AB - BACKGROUND: Immunoglobulin G4 (IgG4)-associated diseases mostly involve the
pancreaticobiliary tree and pancreatic parenchyma. This disease complex is
characterized by marked response to corticosteroid therapy and response to
steroids is incorporated in the diagnostic algorithm of IgG4 associated diseases.
However, there is much unknown about the sequences and duration of healing during
the corticosteroid therapy in the literature. CASE REPORT: In this case report,
we report a young male patient with IgG4 associated extrahepatic biliary
stricture and autoimmune pancreatitis successfully treated with corticosteroids.
Recovery in the laboratory and radiological findings seemed to correlate well
with the decrease in serum IgG4 levels in this patient. We also discussed
sequences and the duration of healing in the pancreaticobiliary tree and
pancreatic parenchymal manifestations in this case report. CONCLUSION: There is a
gap in our knowledge about the evaluation of response criteria after steroid
trial with regard to the duration and sequences of healing in the
pancreaticobiliary involvement in diagnosing IgG4-related biliary and pancreatic
diseases.
PMID- 27606145
TI - The Ewing's Sarcoma Family of Tumors of Urinary Bladder: A Case Report and Review
of the Literature.
AB - BACKGROUND: Only 15 cases of Ewing's Sarcoma (EWS) family of tumors of urinary
bladder have been documented in the literature to date. CASE REPORT: We presented
here a 38 year-old female with primary urinary bladder EWS with no distant
metastases. She had presented with macroscopic hematuria and had undergone
transurethral resection of the tumor within the following week. Microscopic
examination revealed a tumor diffusely infiltrating the lamina propria and
muscularis propria under an intact urothelium, which was composed of small round
blue cells with scant cytoplasm, monotonous round or oval nuclei, stippled
chromatin and small nucleoli. Immunohistochemistry showed strong vimentin,
synaptophysin and membranous CD99 expression by the tumor. Fluorescent in situ
hybridization analysis displayed the EWSR1 rearrangement. Radical cystectomy with
total abdominal hysterectomy and bilateral salpingo-oophorectomy, extended lymph
node dissection, and ileal conduit were performed. As adjuvant chemotherapy, she
received vincristine, doxorubicin, cyclophosphamide and mesna, alternating with
courses of etoposide, iphosphamide and mesna. She is alive and well with no
evidence of disease 14 months after the surgery. CONCLUSION: Surgery supported
with chemotherapy should be considered as an option, especially in advanced
Ewing's sarcoma family of tumors of urinary bladder.
PMID- 27606146
TI - A 3 Year-Old Male Child Ingested Approximately 750 Grams of Elemental Mercury.
AB - BACKGROUND: The oral ingestion of elemental mercury is unlikely to cause systemic
toxicity, as it is poorly absorbed through the gastrointestinal system. However,
abnormal gastrointestinal function or anatomy may allow elemental mercury into
the bloodstream and the peritoneal space. Systemic effects of massive oral intake
of mercury have rarely been reported. CASE REPORT: In this paper, we are
presenting the highest single oral intake of elemental mercury by a child aged 3
years. A Libyan boy aged 3 years ingested approximately 750 grams of elemental
mercury and was still asymptomatic. CONCLUSION: The patient had no existing
disease or abnormal gastrointestinal function or anatomy. The physical
examination was normal. His serum mercury level was 91 ug/L (normal: <5 ug/L),
and he showed no clinical manifestations. Exposure to mercury in children through
different circumstances remains a likely occurrence.
PMID- 27606147
TI - Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old
Girl.
AB - BACKGROUND: Kawasaki disease is a systemic vasculitis predominately affecting
coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course
of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis
occurring during the acute phase of Kawasaki disease have been reported. CASE
REPORT: We report here a 4 month-old girl with diffuse coronary ectasia and
secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of
incomplete Kawasaki disease. CONCLUSION: Due to the large overlap in clinical
symptoms, the presence of atypical findings for Kawasaki disease should suggest
the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients.
PMID- 27606148
TI - Osteoma and Ectopic Tooth of the Left Maxillary Sinus: A Unique Coexistence.
AB - BACKGROUND: Ectopic eruption of a tooth or osteoma rarely occurs within the
maxillary sinus. Coexistence of these two rare entities in the maxillary sinus
has never been reported in the English literature. CASE REPORT: Herein, we
present a 21 year-old male patient with osteoma and ectopic tooth in the left
maxillary sinus treated with the removal of the ectopic tooth by endoscopic sinus
surgery and excision of the osteoma by the Caldwell-Luc procedure. CONCLUSION:
Unique coexistence of two different entities in the maxillary sinus is most
likely due to pediatric facial trauma. Pediatric patients with maxillofacial
trauma should be carefully watched for dental injury both clinically and
radiologically.
PMID- 27606149
TI - Melanocytic Nevus of the Tarsal Conjunctiva.
AB - BACKGROUND: Melanocytic nevus is a rare occurrence in the tarsal conjunctiva and
only 7 well-described cases have been reported previously in the English
literature. CASE REPORT: The medical records of 4 patients with tarsal
conjunctival melanocytic nevus were reviewed, together with the relevant
literature. All patients (3 women and 1 man; age range: 17 - 40 years) had been
referred with a suspicion of melanoma. There was one tarsal nevus in the lower
eyelid in 3 patients and 2 nevi in the upper eyelid in 1 patient. All lesions
were darkly pigmented with irregular borders and were associated with a history
of a recent growth in size. An intralesional cyst was present in 1 nevus only.
After surgical excision, no recurrence or complication occurred during the follow
up period (range: 7 - 48 months). CONCLUSION: Tarsal melanocytic nevus has been
described in detail in 11 cases, including these 4 cases, in the English
literature. The lesion arose from the lower eyelid in all cases except one.
Tarsal melanocytic nevi may frequently display clinical features suggesting
melanoma, such as advanced patient age, recent growth, dark and irregular
pigmentation, nodularity, hypervascularity, and the absence of an intralesional
cyst. After total excision, nevus recurrence or malignant transformation has not
been reported.
PMID- 27606150
TI - Complicated Weil Disease.
PMID- 27606151
TI - Comorbidities must Be Considered in Mean Platelet Volume Measurements in Patients
with Adnexial Torsion.
PMID- 27606152
TI - Letter to the Editor for 'Neutrophil-to-Lymphocyte Ratio as a Marker in Patients
with Non-arteritic Anterior Ischemic Optic Neuropathy'.
PMID- 27606153
TI - Diagnostic tests for syphilis: New tests and new algorithms.
AB - Syphilis is a sexually transmitted infection caused by Treponema pallidum. A
total of 13,106 cases of primary and secondary syphilis were reported in the
United States in 2011 and the rate of infection has increased in subgroups,
particularly men who have sex with men. The disease is mainly diagnosed through
clinical findings and serologic testing. However, no single serologic test of
syphilis is sufficient. Hence, the serologic diagnosis of syphilis requires the
detection of 2 types of antibodies (nontreponemal antibodies and treponemal
antibodies). The paradigm in syphilis testing has recently shifted in many
centers to screen with a treponemal antibody test, reflexing to a nontreponemal
test if the treponemal antibody test is positive. This reverse of the traditional
algorithm may not be widely recognized among clinicians.
PMID- 27606154
TI - Modeling and experimental verification of a new muffler based on the theory of
quarter-wavelength tube and the Helmholtz muffler.
AB - To address the problem of low frequency noise of the internal combustion engine,
several existing muffler design methods, such as the theory of the quarter
wavelength tube and the Helmholtz muffler, were examined and compared. This paper
proposes a new type of muffler design method, which has the advantages of both
the quarter-wavelength tube and the Helmholtz muffler. An example is carried out
to illustrate the analysis of original signal, the design of the new muffler and
the improvement of the in-car noise. The transmission loss of the new muffler is
studied by theoretical method and finite element method. The vehicle test of the
new muffler demonstrates excellent performance with a wider noise elimination
frequency band and smaller radial size.
PMID- 27606155
TI - Identical wave forms of vena cava and pulmonary artery during pulmonary artery
catheter insertion due to kinking: a case report of a rare complication.
AB - BACKGROUND: We experienced a rare malposition of a pulmonary artery catheter due
to kinking in a 63-year-old male who was scheduled for an off-pump coronary
artery by-pass graft. FINDINGS: Given the difficulty to obtain stable pulmonary
artery waveform, we discovered that the two waveforms of the distal and proximal
ports of the pulmonary artery catheter were completely identical. Subsequent
fluoroscopy revealed that because the catheter had formed a kink around the apex
of the right ventricle, the distal port faced the proximal port of the catheter.
CONCLUSIONS: We recommend that both ports of the pulmonary artery catheter need
to be monitored simultaneously in case neither portable fluoroscopy nor
transesophageal echo is available.
PMID- 27606157
TI - Calculation of eigenvalues of Sturm-Liouville equation for simulating
hydrodynamic soliton generated by a piston wave maker.
AB - This paper focuses on the mathematical study of the existence of solitary gravity
waves (solitons) and their characteristics (amplitude, velocity, [Formula: see
text]) generated by a piston wave maker lying upstream of a horizontal channel.
The mathematical model requires both incompressibility condition, irrotational
flow of no viscous fluid and Lagrange coordinates. By using both the inverse
scattering method and a given initial potential [Formula: see text] we can
transform the KdV equation into Sturm-Liouville spectral problem. The latter
problem amounts to find negative discrete eigenvalues [Formula: see text] and
associated eigenfunctions [Formula: see text], where each calculated eigenvalue
[Formula: see text] gives a soliton and the profile of the free surface. For
solving this problem, we can use the Runge-Kutta method. For illustration, two
examples of the wave maker movement are proposed. The numerical simulations show
that the perturbation of wave maker with hyperbolic tangent displacement under
physical conditions affect the number of solitons emitted.
PMID- 27606156
TI - Association between SLCO1B1 -521T>C and -388A>G polymorphisms and risk of statin
induced adverse drug reactions: A meta-analysis.
AB - An increasing number of studies have investigated the association between SLCO1B1
-521T>C and -388A>G polymorphisms and the risk of statin-induced adverse drug
reactions (ADRs), but the results have been inconsistent. This meta-analysis was
performed to gain more insight into the relationship. PubMed, Embase, Cochrane
Library and Web of Science were searched for relevant articles published before
March 5th, 2015. The quality of included studies was evaluated by the Newcastle
Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios
[HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess
the association in overall and subgroup analyses for various genetic models.
Begg's rank correlation test and Egger's linear regression test were used to
examine the publication bias. A total of nine cohort and four case-control
studies involving 11, 246 statin users, of whom 2, 355 developing ADRs were
included in the analysis. Combined analysis revealed a significant association
between the SLCO1B1-521T>C polymorphism and increased risk for ADRs caused by
various statins, but the synthesis heterogeneity was generally large (dominant
model: pooled effect estimate = 1.85, 95 % CI 1.20-2.85, P = 0.005; I (2) = 80.70
%, Pheterogeneity < 0.001). Subgroup analysis by statin type showed that the ADRs
risk was significantly elevated among simvastatin users (dominant model: pooled
effect estimate = 3.43, 95 % CI 1.80-6.52, P = 0.001; I (2) = 59.60 %,
Pheterogeneity = 0.060), but not among atorvastatin users. No significant
relationship was found between the -388A>G polymorphism and ADRs caused by
various statins (dominant model: pooled effect estimate = 0.94, 95 % CI 0.79
1.13, P = 0.526; I (2) = 40.10 %, Pheterogeneity = 0.196). The meta-analysis
suggests that SLCO1B1 -521T>C polymorphism may be a risk factor for statin
induced ADRs, especially in simvastatin therapy. Conversely, there may be no
significant association for -388A>G polymorphism.
PMID- 27606159
TI - Pleth variability index and respiratory system compliance to direct PEEP settings
in mechanically ventilated patients, an exploratory study.
AB - OBJECTIVES: To analyze the ability of pleth variability index (PVI) and
respiratory system compliance (RSC) on evaluating the hemodynamic and respiratory
effects of positive end expiratory pressure (PEEP), then to direct PEEP settings
in mechanically ventilated critical patients. METHODS: We studied 22 mechanically
ventilated critical patients in the intensive care unit. Patients were monitored
with classical monitor and a pulse co-oximeter, with pulse sensors attached to
patients' index fingers. Hemodynamic data [heart rate (HR), perfusion index (PI),
PVI, central venous pressure (CVP), mean arterial pressure (MAP), peripheral
blood oxygen saturation (SPO2), peripheral blood oxygen content (SPOC) and
peripheral blood hemoglobin (SPHB)] as well as the respiratory data [respiratory
rate (RR), tidal volume (VT), RSC and controlled airway pressure] were recorded
for 15 min each at 3 different levels of PEEP (0, 5 and 10 cmH2O). RESULTS:
Different levels of PEEP (0, 5 and 10 cmH2O) had no obvious effect on RR, HR,
MAP, SPO2 and SPOC. However, 10 cmH2O PEEP induced significant hemodynamic
disturbances, including decreases of PI, and increases of both PVI and CVP.
Meanwhile, 5 cmH2O PEEP induced no significant changes on hemodynamics such as
CVP, PI and PVI, but improved the RSC. CONCLUSIONS: RSC and PVI may be useful in
detecting the hemodynamic and respiratory effects of PEEP, thus may help
clinicians individualize PEEP settings in mechanically ventilated patients.
PMID- 27606158
TI - Prognosis value of Hypoxia-inducible factor-1alpha expression in patients with
bone and soft tissue sarcoma: a meta-analysis.
AB - The prognostic significance of Hypoxia-inducible factor-1alpha (HIF-1alpha) in
patients with bone and soft tissue sarcoma remains controversial. To investigate
the impact of its expression on survival outcomes, we performed a meta-analysis.
Comprehensive literature searches were conducted in PubMed, Web of Science,
Embase and Cochrane Library. A total of 16 studies published from 2006 to 2015
were included. We found that expression of HIF-1alpha was significantly
associated with higher rate of metastasis (RR 3.21, 95 % CI 2.12-4.84, P <
0.001), poorer overall survival (HR 2.05, 95 % CI 1.51-2.77, P < 0.001) and
poorer disease-free survival (HR 2.05, 95 % CI 1.55-2.70, P < 0.001). In
addition, when subgroup analysis was conducted according to histology type, the
significant correlations to poor overall survival and disease-free survival were
also observed in patients with osteosarcoma, chondrosarcoma and soft tissue
sarcoma. Publication bias was not found and sensitivity analysis showed the
results were stable. In conclusion, HIF-1alpha expression might be an effective
predicative factor of poor prognosis for bone and soft tissue sarcoma.
PMID- 27606160
TI - Right atrial isomerism in children older than 3 years.
AB - BACKGROUND: There is a high mortality in infants with right atrial isomerism
(RAI). However, less is known about outcome in older children with RAI. This
study sought to evaluate those patients with RAI who survived older than 3 years
of age without surgical intervention. RESULTS: A total of 33 consecutive patients
(20 males) were enrolled in the study, mean age 6 years (range 3-32). None of the
patients had surgical intervention for the RAI before age 3. Cardiac
abnormalities include altered cardiac position (39 %), atrioventricular valve
anomaly (87 %), single or functional single ventricle (55 %),
pulmonary/subpulmonary obstruction (97 %), abnormal origin of the aorta (100 %),
bilateral superior vena cava (67 %), and anomalous pulmonary venous drainage (66
%). Surgical intervention was performed after 3 years of age in 20 patients (61
%). None of them planned or had biventricular repair performed. 10 patients
underwent the total cavopulmonary connection procedure, including four (40 %) who
had atrioventricular valve (AVV) repair at the same time [all with common
atrioventricular valve (CAVV)]. One patient died the day after the operation. A
total of 69 % of patients with a CAVV had moderate or severe regurgitation, while
27 % with a single atrioventricular valve had moderate or severe regurgitation.
CONCLUSION: Patients with RAI who have survived to early childhood without
surgical intervention have complex cardiac abnormalities. Survival after single
stage total cavopulmonary connection is good but AVV repair is common.
PMID- 27606161
TI - Microwave ablation of malignant extremity bone tumors.
AB - BACKGROUND: The current application of limb salvage process has some unsolved
problems, such as prosthesis loosening, which severely limits the function of the
preserved limbs. Innovative approaches are needed to further improve functional
outcome. PATIENTS AND METHODS: Instead of en-bloc resection of tumor-bearing
bone, it is dissected from the surrounding normal tissues, followed by
devitalizing the bone segment and the extra-cortical bulk by microwave induced
hyperthermia in situ through the antenna array. From May 1999 to March 2012, 544
patients with malignant bone tumors of the extremities were treated by the novel
method. RESULTS: The over 3-year survival rate was 59.1 % for high-grade
malignancy, 88.7 % for low-grade malignancy. In the majority of the patients,
cosmetic and useful limbs were preserved. Local recurrence rate was 9.8 % for the
high grade malignancy (mainly occurred at the early stage of the research). The
overall fracture rate was 2.6 %. Deep infection rate was 1.8 %. The complication
rate is lower than the literature reports. After heat necrosis, the dead bone
maintains both the osteoconduction and osteoinduction properties. CONCLUSIONS:
The application of microwave induced hyperthermia for treatment of malignant bone
tumors, except the late diagnosed cases who's tumor-bearing bone was destroyed
too severe to do biological reconstruction, is an effective, simple, and
inexpensive method. The oncological and functional results are encouraging.
PMID- 27606162
TI - Controlling and Predicting Unpredictable Behavior.
AB - Behaving predictably can be advantageous in some situations, but unpredictability
can also be advantageous in some competitive situations like sports, games, and
war. Can, however, unpredictable behavior be conditioned? If a contingency of
reinforcement based upon the predictability of behavior generates unpredictable
responding, is it possible to conclude that predictability is itself a
reinforceable dimension of behavior? In this paper, I address these questions by
examining the concept and measures of predictability and the procedures generally
used to increase unpredictable responding. I discuss the hypothesis that
contingencies based on response frequency shape the generalized operant "to vary"
and an alternative hypothesis that such contingencies generate unpredictable
responding by balancing the strength of each alternative response over time. I
discuss the findings that support the balance hypothesis as well as its
limitations. I conclude that the two alternative hypotheses may be complementary
in explaining unpredictable responding.
PMID- 27606163
TI - Commentary on Malone: Who Founded Behaviorism?
AB - Malone (The Behavior Analyst, 37, 1-12 2014) argued that the emergence of
behaviorism was inevitable with or without Watson's participation, mainly because
protobehavioral ideas and dissatisfaction with classical structuralism were
already widespread. However, the first premise is questionable because many of
the ideas Malone cited were consistent with structuralism rather than
behaviorism, and even if both premises were true they would not make the
emergence of behaviorism-or anything else-inevitable. Historical evidence for
inevitability is always retrospective and therefore always allows the logical
fallacy of "after this, therefore because of this." In the relevant real world
Watson existed, he was a psychologist, he was the first to publish an article
that described a "behaviorism," and he promoted his behaviorism in later works.
Stories about what would have happened without Watson's participation are
therefore counterfactual and this lack of historicity makes the stories fictional
rather than scientific. In the real world, Watson founded behaviorism.
PMID- 27606165
TI - The Divergent Paths of Behavior Analysis and Psychology: Vive la Difference!
AB - Twenty years ago I suggested that behavior analysts could effect a quiet and
covert takeover of the American Psychological Association (APA). I gave as
precedents the operation of similar initiatives in the nineteenth and twentieth
centuries, the Darwinian-inspired X-Club, and the psychoanalytically-oriented
Secret Ring. Though a conscientious program of working within established APA
bylaws and rules, behavior analysts could ensure that behavior analysts were
nominated for every significant elective position within the APA, and move to get
their colleagues placed in appointive positions, such as journal editorships,
review boards, and major committees. This would be one approach to remake
psychology along behavioral lines, which was an early ambition of B. F. Skinner.
The community of behavior analysts ignored my suggestion, and instead pursued the
path of creating an independent discipline of practitioners, one with its own
degree-granting programs, conventions, journals, and legal regulation. This
effort has been immensely successful, although much critical work remains to be
done. In retrospect, I was wrong to suggest changing psychology from within, and
I have been delighted to witness the emergence of our new and independent field.
PMID- 27606164
TI - How Hume's Philosophy Informed Radical Behaviorism.
AB - The present paper analyzes consistencies between the philosophical systems of
David Hume and B. F. Skinner, focusing on their conceptualization of causality
and attitudes about scientific behavior. The ideas that Hume initially advanced
were further developed in Skinner's writings and shaped the behavior-analytic
approach to scientific behavior. Tracing Skinner's logical antecedents allows for
additional historical and philosophical clarity when examining the development of
radical behaviorism.
PMID- 27606166
TI - Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners.
AB - While no single factor accounts for the significant increases in overweight and
obesity that have emerged during the past several decades, evidence now suggests
that sugars, in general, and sugar-sweetened beverages, in particular, may be
especially problematic. One response to this concern has been an explosion in the
availability and use of noncaloric sweeteners as replacements for sugar. While
consumers have been led to believe that such substitutes are healthy, long-term
epidemiological data in a number of cohorts have documented increased risk for
negative outcomes like type 2 diabetes, heart disease, and stroke among users of
artificial sweeteners. Experimental data from animals has provided several
plausible mechanisms that could explain this counterintuitive relationship. In
particular, my research has demonstrated that artificial sweeteners appear to
interfere with basic learned, predictive relations between sweet tastes and post
ingestive consequences such as the delivery of energy. By interfering with these
relations, artificial sweeteners inhibit anticipatory responses that normally
serve to maintain physiological homeostasis, and over the long term, this
interference could result in negative health effects like those seen in the human
cohort studies. These data suggest that reducing the consumption of all
sweeteners is advisable to promote better health.
PMID- 27606167
TI - An Analysis of Feedback from a Behavior Analytic Perspective.
AB - The present paper presents a systematic analysis from a behavior analytic
perspective of procedures termed feedback. Although feedback procedures are
widely reported in the discipline of psychology, including in the field of
behavior analysis, feedback is neither consistently defined nor analyzed.
Feedback is frequently treated as a principle of behavior; however, its effects
are rarely analyzed in terms of well-established principles of learning and
behavior analysis. On the assumption that effectiveness of feedback procedures
would be enhanced when their use is informed by these principles, we sought to
provide a conceptually systematic account of feedback effects in terms of operant
conditioning principles. In the first comprehensive review of this type, we
compare feedback procedures with those of well-defined operant procedures. We
also compare the functional relations that have been observed between parameters
of consequence delivery and behavior under both feedback and operant procedures.
The similarities observed in the preceding analyses suggest that processes
revealed in operant conditioning procedures are sufficient to explain the
phenomena observed in studies on feedback.
PMID- 27606168
TI - A General Methodology for the Translation of Behavioral Terms into Vernacular
Languages.
AB - As the field of behavior analysis expands internationally, the need for
comprehensive and systematic glossaries of behavioral terms in the vernacular
languages of professionals and clients becomes crucial. We created a Spanish
language glossary of behavior-analytic terms by developing and employing a
systematic set of decision-making rules for the inclusion of terms. We then
submitted the preliminary translation to a multi-national advisory committee to
evaluate the transnational acceptability of the glossary. This method led to a
translated corpus of over 1200 behavioral terms. The end products of this work
included the following: (a) a Spanish-language glossary of behavior analytic
terms that are publicly available over the Internet through the Behavior Analyst
Certification Board and (b) a set of translation guidelines summarized here that
may be useful for the development of glossaries of behavioral terms into other
vernacular languages.
PMID- 27606169
TI - A Historical Perspective on the Future of Behavior Science.
AB - Like all natural sciences, behavior science has much to offer toward an
understanding of the world. The extent to which the promise of behavior science
is realized, though, depends upon the extent to which we keep what we know before
us. This paper considers fundamental concepts in behavior science, including the
concepts of behavior, stimulation, setting conditions, and language. In
considering these concepts, we revisit comments from B. F. Skinner and J. R.
Kantor and also consider some areas of behavior analytic research and the
implications they have for reconsidering long-held assumptions about the analysis
of behavior. We hope that, in considering our foundations, the vitality and
strength of the discipline might be enhanced, our impact on science improved, and
our future secured.
PMID- 27606170
TI - Trends in Behavior-Analytic Gambling Research and Treatment.
AB - The purpose of the present review was to analyze research outcomes for all
gambling studies reported in the behavior analysis literature. We used the search
term "gambling" to identify articles that were published in behaviorally oriented
journals between the years 1992 and 2012 and categorized the content of each
article as empirical or conceptual. Next, we examined and categorized the
empirical articles by inclusion of an experimental manipulation and treatment to
alleviate at least some aspect of pathological gambling, participant population
used, type of gambling task employed in the research, whether the participants in
the study actually gambled, and the behavioral phenomena of interest. The results
show that the rate of publication of gambling research has increased in the last
6 years, and a vast majority of articles are empirical. Of the empirical
articles, examinations of treatment techniques or methods are scarce; slot
machine play is the most represented form of gambling, and slightly greater than
half of the research included compensation based on gambling outcomes within
experiments. We discuss implications and future directions based on these
observations of the published literature.
PMID- 27606172
TI - On the Distinction Between the Motivating Operation and Setting Event Concepts.
AB - In recent decades, behavior analysts have generally used two different concepts
to speak about motivational influences on operant contingencies: setting event
and motivating operation. Although both concepts still appear in the contemporary
behavior-analytic literature and were designed to address the same antecedent
phenomena, the concepts are quite different. The purpose of the present article
is to describe and distinguish the concepts and to illustrate their current
usage.
PMID- 27606171
TI - JEAB Research Over Time: Species Used, Experimental Designs, Statistical
Analyses, and Sex of Subjects.
AB - We examined the species used as subjects in every article published in the
Journal of the Experimental Analysis of Behavior (JEAB) from 1958 through 2013.
We also determined the sex of subjects in every article with human subjects (N =
524) and in an equal number of randomly selected articles with nonhuman subjects,
as well as the general type of experimental designs used. Finally, the percentage
of articles reporting an inferential statistic was determined at 5-year
intervals. In all, 35,317 subjects were studied in 3,084 articles; pigeons ranked
first and humans second in number used. Within-subject experimental designs were
more popular than between-subjects designs regardless of whether human or
nonhuman subjects were studied but were used in a higher percentage of articles
with nonhumans (75.4 %) than in articles with humans (68.2 %). The percentage of
articles reporting an inferential statistic has increased over time, and more
than half of the articles published in 2005 and 2010 reported one. Researchers
who publish in JEAB frequently depart from Skinner's preferred research strategy,
but it is not clear whether such departures are harmful. Finally, the sex of
subjects was not reported in a sizable percentage of articles with both human and
nonhuman subjects. This is an unfortunate oversight.
PMID- 27606173
TI - Prominent Women in Behavior Analysis: An Introduction.
PMID- 27606174
TI - A Career in Behavior Analysis: Notes from the Journey.
PMID- 27606175
TI - My Mentors and their Influences on My Career.
PMID- 27606176
TI - A Challenging and Satisfying Career in Basic Science.
PMID- 27606177
TI - Influences on My Early Academic Career.
PMID- 27606178
TI - Opportunities and Some Lessons Learned from a Career in Behavior Analysis.
PMID- 27606179
TI - Joy and Fulfillment as a Female Behavior Analyst.
PMID- 27606180
TI - Stereo Knobs and Swing Sets: Falling in Love with the Science of Behavior.
PMID- 27606181
TI - Why Brains Are Not Computers, Why Behaviorism Is Not Satanism, and Why Dolphins
Are Not Aquatic Apes.
AB - Modern psychology has, to all intents and purposes, become synonymous with
cognitive psychology, with an emphasis on the idea that the brain is a form of
computer, whose job is to take in sensory input, process information, and produce
motor output. This places the brain at a remove from both the body and
environment and denies the intimate connection that exists between them. As a
result, a great injustice is done to both human and nonhuman animals: On the one
hand, we fail to recognize the distinctive nature of nonhuman cognition, and on
the other hand, we continue to promote a somewhat misleading view of human
psychological capacities. Here, I suggest a more mutualistic, embodied, enactive
view might allow us to ask more interesting questions about how animals of all
kinds come to know their worlds, in ways that avoid the (inevitable)
anthropocentric baggage of the cognitivist viewpoint.
PMID- 27606182
TI - What Studying Leadership Can Teach Us About the Science of Behavior.
AB - Throughout history, individuals have changed the world in significant ways,
forging new paths; demonstrating remarkable capacity to inspire others to follow;
and repeatedly showing independence, resilience, consistency, and commitment to
principle. However, significant cultural change is rarely accomplished single
handedly; instead, it results from the complex and dynamic interaction of groups
of individuals. To illustrate how leaders participate in cultural phenomena, I
describe how a few individuals helped to establish the Cold War. In this
analysis, I distinguish two types of cultural phenomena: metacontingencies,
involving lineages of interlocking behavioral contingencies, and cultural cusps,
involving complicated, unique, and nonreplicable interrelations between
individuals and circumstances. I conclude that by analyzing leaders' actions and
their results, we can appreciate that cultural and behavioral phenomena are
different, and although cultural phenomena are inherently complex and in many
cases do not lend themselves to replication, not only should the science of
behavior account for them, cultural phenomena should also constitute a major area
of behavior analysis study and application.
PMID- 27606183
TI - Strategies to Position Behavior Analysis as the Contemporary Science of What
Works in Behavior Change.
AB - The negative perception of behavior analysis by the public, and conveyed in mass
media, is well-recognized by the professional community of behavior analysts.
Several strategies for correcting this perception have been deployed in the field
by organizational behavior management practitioners, in particular, with
encouraging results. These strategies include (a) reframing behaviorism in a more
resonant format, (b) pushing direct outcome comparisons between behavior analysis
and its rivals, and (c) playing up the "warm and fuzzy" side of behavior analysis
(see Freedman 2015, in this issue, for a thorough description of these
strategies). This article outlines three additional strategies that the author
believes will position behavior analysis as a "contemporary science of what works
in behavior change." These new strategies are (a) creating a cohesive, easily
understandable framework; (b) personally communicating a more contemporary,
sophisticated message; and
PMID- 27606184
TI - Improving Public Perception of Behavior Analysis.
AB - The potential impact of behavior analysis is limited by the public's dim
awareness of the field. The mass media rarely cover behavior analysis, other than
to echo inaccurate negative stereotypes about control and punishment. The media
instead play up appealing but less-evidence-based approaches to problems, a key
example being the touting of dubious diets over behavioral approaches to losing
excess weight. These sorts of claims distort or skirt scientific evidence,
undercutting the fidelity of behavior analysis to scientific rigor. Strategies
for better connecting behavior analysis with the public might include reframing
the field's techniques and principles in friendlier, more resonant form; pushing
direct outcome comparisons between behavior analysis and its rivals in simple
terms; and playing up the "warm and fuzzy" side of behavior analysis.
PMID- 27606185
TI - Contributions of Behavioral Systems Science to Leadership for a New Progressive
Movement.
AB - We argue in this paper that we are in the midst of a period in which fundamental
global change will be required if societies and many species, perhaps even our
own, are to survive. The realities are inescapable, and the potential
implications are likely to affect nearly every dimension of human life in the USA
and globally. Current trends are discouraging and will be extraordinarily
difficult to shift, given global structural realities. It is hard to imagine a
time when effective leadership is more necessary or will be more challenging. Our
thesis here is that behavioral systems science can contribute in meaningful ways
to shaping and sustaining such leadership, leadership required to advance a new
progressive movement.
PMID- 27606186
TI - Editorial: a Very Special Issue.
PMID- 27606187
TI - The Scientific Image in Behavior Analysis.
AB - Throughout the history of science, the scientific image has played a significant
role in communication. With recent developments in computing technology, there
has been an increase in the kinds of opportunities now available for scientists
to communicate in more sophisticated ways. Within behavior analysis, though, we
are only just beginning to appreciate the importance of going beyond the printing
press to elucidate basic principles of behavior. The aim of this manuscript is to
stimulate appreciation of both the role of the scientific image and the
opportunities provided by a quick response code (QR code) for enhancing the
functionality of the printed page. I discuss the limitations of imagery in
behavior analysis ("Introduction"), and I show examples of what can be done with
animations and multimedia for teaching philosophical issues that arise when
teaching about private events ("Private Events 1 and 2"). Animations are also
useful for bypassing ethical issues when showing examples of challenging behavior
("Challenging Behavior"). Each of these topics can be accessed only by scanning
the QR code provided. This contingency has been arranged to help the reader
embrace this new technology. In so doing, I hope to show its potential for going
beyond the limitations of the printing press.
PMID- 27606188
TI - The Other Shoe: An Early Operant Conditioning Chamber for Pigeons.
AB - We describe an early operant conditioning chamber fabricated by Harvard
University instrument maker Ralph Gerbrands and shipped to Japan in 1952 in
response to a request of Professor B. F. Skinner by Japanese psychologists. It is
a rare example, perhaps the earliest still physically existing, of such a chamber
for use with pigeons. Although the overall structure and many of the components
are similar to contemporary pigeon chambers, several differences are noted and
contrasted to evolutionary changes in this most important laboratory tool in the
experimental analysis of behavior. The chamber also is testimony to the early
internationalization of behavior analysis.
PMID- 27606189
TI - Leadership and Cultural Change: Implications for Behavior Analysis.
PMID- 27606190
TI - The Need for a More Effective Science of Cultural Practices.
AB - Behavior analysis has produced a robust theoretical analysis of the contingencies
involved in cultural evolution. Yet, thus far, the empirical yield of this work
remains quite limited. With this paper, I attempt to provide specific examples of
the ways to advance an experimental analysis of the contingencies involved in
cultural evolution. I begin with a review of the theoretical analyses developed
by behavior analysts and other contextually oriented scientists. Next, I submit
that, if the goal of our science is both predicting and influencing cultural
phenomena, we must produce experimental analyses of the impact of meta
contingencies on organizations' practices. There is no more pressing reason for
doing this than the threat of climate change posed by the continuing growth in
human use of fossil fuels. Therefore, the paper provides an analysis of the
contingencies influencing organizational practices now affecting continued use of
fossil fuels and the contingencies for organizations seeking to prevent their
use. One concrete step to advance a science of cultural change relevant to
climate change would be to create a database of organizations that are promoting
vs. working to prevent fossil fuel consumption and the consequences that seem to
maintain their practices. I call for experimental analysis of the impact of
altering consequences for these practices and for experimental analyses of
interventions intended to change the norms, values, and behavior of
organizational leaders who can influence fossil fuel consumption. I then discuss
the role of prosocial behavior and values in affecting behavior relevant to
reducing fossil fuel consumption because the empirical evidence shows that
prosociality favors more "green" behavior. Recent advances in prevention research
have identified interventions to promote prosociality, but we need experimental
analyses of how advocacy organizations can be more effective in getting these
interventions widely adopted.
PMID- 27606191
TI - Behaviorism and Society.
AB - A probable list of causes for the limited acceptance of behaviorism in our
society is identified. This is followed by a summary review of the proposed
solutions identified in other papers in this special issue of The Behavior
Analyst, most of which relate to either better marketing of either the behavior
analytic process or the results achieved as a consequence. One paper proposes a
more broad conception of behavior analysis. This paper endorses the solutions
identified in previous papers and then goes on to propose an even more broad
conception of behavior analysis and makes the point that behavior analysis is
unlikely to flourish unless behavior analysts understand a good deal more about
the cultural and other contextual features of the environments in which they
work.
PMID- 27606192
TI - Editorial: An Introduction to the Special Section on Diverse Origins of Graduate
Training Programs in Behavior Analysis.
PMID- 27606193
TI - Necessity and Opportunity: the 1-Year Master's ABA Program at Auburn University.
AB - The Auburn University Master of Science program in Applied Behavior Analysis was
designed to accommodate not only the requirements of the Behavior Analyst
Certification Board for approved course sequences and practicum training, but
unavoidable limitations in faculty and other resources. These limitations were
incompatible with the more traditional 2-year curriculum model, so a 1-year
program was designed that met the necessary conditions. This article describes
the resulting academic and practicum curriculum, the key funding mechanisms that
allowed the program to develop, and the opportunities and benefits that this
model afforded.
PMID- 27606194
TI - Caldwell University's Department of Applied Behavior Analysis.
AB - Since 2004, faculty members at Caldwell University have developed three
successful graduate programs in Applied Behavior Analysis (i.e., PhD, MA, non
degree programs), increased program faculty from two to six members, developed
and operated an on-campus autism center, and begun a stand-alone Applied Behavior
Analysis Department. This paper outlines a number of strategies used to advance
these initiatives, including those associated with an extensive public relations
campaign. We also outline challenges that have limited our programs' growth.
These strategies, along with a consideration of potential challenges, might prove
useful in guiding academicians who are interested in starting their own programs
in behavior analysis.
PMID- 27606195
TI - Conceptualization and Development of the Behavior Analysis Programs at the
Florida Institute of Technology.
AB - We describe the conceptualization and development of the Behavior Analysis
programs at the Florida Institute of Technology (Florida Tech). From its
beginnings as a small master's program in applied behavior analysis (ABA), the
Behavior Analysis programs at Florida Tech have now grown to include three Master
of Science programs across two campuses, a Ph.D. program in Behavior Analysis, an
undergraduate degree (B.A.) in ABA, an online certificate program that has
attracted students internationally, and a hybrid (live and online) Master of Arts
in Professional Behavior Analysis program at several sites around the USA. These
programs are now housed in the first ever School of Behavior Analysis at a Tier
1, nationally ranked private university.
PMID- 27606197
TI - The Origin and Evolution of the Behavior Analysis Program at the University of
Nevada, Reno.
AB - The origins of the Behavior Analysis program at the University of Nevada, Reno by
way of a self-capitalized model through its transition to a more typical graduate
program is described. Details of the original proposal to establish the program
and the funding model are described. Some of the unusual features of the program
executed in this way are discussed, along with problems engendered by the model.
Also included is the diversification of faculty interests over time. The status
of the program, now, after 25 years of operation, is presented.
PMID- 27606196
TI - The Munroe-Meyer Approach: Continuous Integration of Didactic Instruction,
Research, and Clinical Practice.
AB - Increased demand for applied behavior analysis (ABA) services has increased the
need for additional masters-level practitioners and doctoral-level academicians
and clinical directors. Based on these needs, the University of Nebraska Medical
Center's (UNMC) Munroe-Meyer Institute has developed a PhD program. The academic
structure at UNMC allowed us to create our PhD program in a relatively quick and
efficient manner. Our PhD program has many unique features, including (a) close
integration of didactic instruction with clinical and research training provided
by leading experts in ABA in which students immediately apply concepts introduced
in the classroom during coordinated clinical and research practica; (b)
structured grant writing training in which students learn to write and submit an
NIH-level grant;
PMID- 27606198
TI - The Functional Independence of Mands and Tacts: Has It Been Demonstrated
Empirically?
AB - Recently, there has been a proliferation of research on the functional
independence of two of Skinner's (1957) verbal operants, the mand, and the tact.
This research has produced highly variable results. In this article, we provide a
critical review of the literature on mand-tact independence, a literature that
has implications for both theory and practice. Included in the review are 17
studies with a total of 66 participants who were tested for mand emergence
following tact training, tact emergence following mand training, or both, and 11
additional studies that systematically manipulated variables expected to affect
the outcomes of such tests. A primary finding is that most studies to date suffer
from problems with construct validity. However, it may be justifiable to conclude
that the literature provides at least weak support for the functional
independence of mands and tacts. Future investigators should avoid the major
construct validity pitfalls described in this article, describe participant
characteristics more thoroughly, and consider alternative approaches to studying
mand-tact independence.
PMID- 27606199
TI - Evaluating the Emergence of Reverse Intraverbals in Children with Autism.
AB - Verbal behavior plays a fundamental role in the development of complex social and
communication skills. Many children diagnosed with autism spectrum disorder
exhibit profound deficiencies in intraverbal repertoires and the development of
social relationships. Recent studies that investigated the effects of intraverbal
training on the emergence of reverse intraverbals produced mixed results (e.g.,
Perez-Gonzalez et al., Journal of Applied Behavior Analysis 40:697-701, 2007)).
In the current study, a multiple-probe design across four participants with
autism was used to evaluate the effects of intraverbal training on the emergence
of reverse intraverbals. Intraverbal training consisted of multiple exemplars
taught concurrently, bidirectional stimulus-response teaching formats, general
case analysis, reinforcement, and a constant prompt delay (CPD) procedure.
Participants were trained on intraverbal targets and probes were conducted to
assess emergence of untaught reverse intraverbals. Three participants
demonstrated the emergence of reverse intraverbals as a result of the intraverbal
training procedures. Social validity and maintenance of target responses and
emergent reverse intraverbals were assessed.
PMID- 27606201
TI - Editorial.
PMID- 27606200
TI - Is the Source of Reinforcement for Naming Multiple Conditioned Reinforcers for
Observing Responses?
AB - Naming refers to the incidental acquisition of word-object relations as listener
and speaker without explicit reinforcement. To investigate possible sources of
reinforcement for naming, we examined the effects of a procedure for conditioning
reinforcement for observing responses on the emergence of naming in children who
previously lacked it. The participants were three 5- to 7-year-old children with
and without diagnoses of autism spectrum disorder. During the intervention,
either visual or auditory stimuli were first conditioned as reinforcers for
observing responses. Then, neutral visual or auditory stimuli were paired with
the conditioned visual or auditory stimuli until both visual and auditory stimuli
acquired reinforcing properties for observing. Following this intervention, the
participants demonstrated naming of stimuli that had been used in pretests for
naming, as well as on a novel set of stimuli. We observed increases in echoic
responding in conjunction with the emergence of naming and conditioned
reinforcement for both observing responses. We interpret the data as suggesting
that listener and speaker repertoires are joined for naming only when both visual
and auditory stimuli reinforce the observing responses of looking and listening
simultaneously.
PMID- 27606202
TI - An Annotated Bibliography of Verbal Behavior Scholarship Published Outside of The
Analysis of Verbal Behavior: 2014.
AB - This annotated bibliography summarizes journal articles on verbal behavior
published outside of The Analysis of Verbal Behavior, the primary journal for
scholarship in this area. Seventeen such articles were published in 2014 and are
annotated as a resource for practitioners, researchers, and educators.
PMID- 27606203
TI - Use of a Modified Chaining Procedure with Textual Prompts to Establish
Intraverbal Storytelling.
AB - Echoic, tact, and textual transfer procedures have been proven successful in
establishing simple intraverbals (Braam and Poling Applied Research in Mental
Retardation, 4, 279-302, 1983; Luciano Applied Research in Mental Retardation,
102, 346-357, 1986; Watkins et al. The Analysis of Verbal Behavior, 7, 69-81,
1989). However, these strategies may be ineffective for some children due to the
complexity of the targeted intraverbals. The current study investigated the use
of a novel procedure which included a modified chaining procedure and textual
prompts to establish intraverbal behavior in the form of telling short stories.
Visual prompts and rule statements were used with some of the participants in
order to produce the desired behavior change. Results indicated that the
procedure was effective for teaching retelling of short stories in three children
with autism.
PMID- 27606204
TI - The Effects of Multiple Exemplar Instruction on the Relation Between Listener and
Intraverbal Categorization Repertoires.
AB - We evaluated the effects of multiple exemplar instruction (MEI) on the relation
between listener and intraverbal categorization repertoires of six typically
developing preschool-age children using a nonconcurrent multiple-probe design
across participants. After failing to emit intraverbal categorization responses
following listener categorization training, participants were exposed to MEI in
the form of alternating response forms (listener and intraverbal) during
categorization training with novel stimulus sets. For two participants for whom
there was some evidence of emergent intraverbal responding, responding was
variable. For the remaining four participants, 32 to 99 MEI trial blocks produced
minimal improvement in responding or no emergent responding at all. The results
are discussed in terms of Skinner's analysis of verbal behavior and naming
theory.
PMID- 27606205
TI - An Evaluation of Instruction in Visual Imagining on the Written Spelling
Performance of Adolescents with Learning Disabilities.
AB - Recent research has evaluated the utility of teaching potentially covert
strategies to mediate overt performance. As an extension of this developing
literature, the current study used a multiple-probe design to evaluate the
effects of instructing in a visual imagining strategy on correct written spelling
responses with three adolescents with various learning disabilities. After the
participants were presented with the textual target stimuli, they were instructed
to imagine the word in their head before writing it down. All three participants
demonstrated improvements in spelling after this instruction, but two of them
required additional consequences to meet the mastery criterion.
PMID- 27606206
TI - Further Analysis of Selection-Based Instruction, Lag Reinforcement Schedules, and
the Emergence of Topography-Based Responses to Interview Questions.
PMID- 27606207
TI - A Comparison of Intraverbal and Listener Training for Children with Autism
Spectrum Disorder.
AB - The present investigation compared acquisition of intraverbals and listener
behavior by function, feature, and class (FFC) for two children with autism
spectrum disorder (ASD). We also measured tacts during listener training to
evaluate whether higher levels of tacts predicted the emergence of intraverbal
behavior following training. The results showed that intraverbal training
required as many or fewer sessions to reach the mastery criterion than listener
training by FFC, and intraverbal training consistently produced emergent listener
behavior. In comparison, listener training by FFC did not consistently lead to
the emergence of intraverbal behavior.
PMID- 27606208
TI - Token Reinforcement of Verbal Responses Controlled by Temporally Removed Verbal
Stimuli.
PMID- 27606209
TI - The Analysis of Verbal Behavior: a Status Update.
AB - We analyzed past volumes of The Analysis of Verbal Behavior (TAVB) to provide a
comprehensive status update after 30 years of publication. Data on TAVB's
content, frequent contributors, and scholarly impact suggest a healthy state of
the journal.
PMID- 27606210
TI - Training Intraverbal Naming to Establish Matching-to-Sample Performances.
AB - The current study evaluated whether training intraverbal naming would be
sufficient to establish visual-visual matching-to-sample (MTS) performances in
college students. In the first experiment, we used a multiple-probe design across
stimulus sets to assess whether six participants could match arbitrary visual
stimuli (AB) after learning to tact their two experimentally defined classes (A'
and B') and then intraverbally relate their names (i.e., "A' goes with B'"). All
participants matched the stimuli accurately after training, as well as emitted
the trained intraverbals. In the second experiment, we used a multiple baseline
design across four participants to assess whether the same training would produce
bi-directional intraverbals in the form of "B' goes with A'," and MTS performance
consistent with symmetry (BA). All participants responded accurately during
matching and intraverbal tests. Across both experiments, participants stated the
trained intraverbals while performing the matching task. Results showed that MTS
performance can be established solely by verbal behavior training.
PMID- 27606211
TI - Using Instructive Feedback to Increase Response Variability During Intraverbal
Training for Children with Autism Spectrum Disorder.
AB - We evaluated the effects of instructive feedback on the variability of
intraverbal responses for two children with autism spectrum disorder.
Specifically, we used an adapted alternating treatments design to compare
participants' novel responses and response combinations during an intraverbal
category program across conditions with and without instructive feedback. During
instructive feedback, secondary targets were presented during the consequence
event of the learning trial and consisted of a therapist's model of response
variability. The results showed that participants engaged in more novel response
combinations during instructive feedback conditions. We discussed the clinical
implications of these results as well as areas for future research.
PMID- 27606212
TI - Recombinative Generalization of Tacts Through Matrix Training with Individuals
with Autism Spectrum Disorder.
AB - Foss (Journal of Experimental Psychology, 76, 450-459, 1968a; Journal of
Experimental Psychology, 77, 341-344, 1968b) compared overlap and non-overlap
instruction to promote recombinative response generalization using a matrix
training procedure. In the present study, we used a similar set of procedures to
teach tacting of kitchen items and prepositions (i.e., relational autoclitics) to
three females ages 13-20, diagnosed with autism spectrum disorder. We taught some
kitchen items/prepositions as tacts (e.g., "the strainer is to the right of the
box") according to a non-overlap instructional sequence. Subsequently, we taught
more combinations in an overlap instructional sequence. Each training procedure
was followed by probes of untrained relations. Two participants demonstrated
recombinative generalization of untrained combinations following the first non
overlap phase, while the third participant demonstrated some response
generalization of untrained relations after a few additional training sequences.
All three participants demonstrated generalized tacting of object components
while two participants showed generalized tacting of preposition components.
PMID- 27606213
TI - Stimulus-Stimulus Pairing to Increase Vocalizations in Children with Language
Delays: a Review.
AB - Stimulus-stimulus pairing (SSP) is a procedure used to increase vocalizations in
children with significant language delays. However, results from studies that
have examined the effectiveness of SSP have been discrepant. The following review
of the literature summarizes the results from 13 experiments published between
1996 and 2014 that used this procedure with children with language delays.
Studies were analyzed across various participant and procedural variables, and an
effect size estimate (nonoverlap of all pairs) was calculated for a portion of
the participants in the studies reviewed. Results indicated an overall moderate
intervention effect for SSP of speech sounds. Recommendations are provided for
future researchers about information to report and potential avenues for future
studies.
PMID- 27606214
TI - The Effects of Auditory Tact and Auditory Imagining Instructions on the Emergence
of Novel Intraverbals.
AB - The current research investigated whether intraverbals would emerge following
auditory tact instruction. Participants were first taught to tact auditory
stimuli by providing the name of the item or animal that produces the sound
(e.g., saying "eagle" when presented with the recording of an eagle cawing).
Following test probes for simple intraverbals as well as intraverbal
categorization participants were taught to tact what each auditory stimulus is
(e.g., saying "caw" when presented with the recording of an eagle cawing).
Following both tact instructional phases, the effects of an auditory imagining
instruction procedure on target intraverbals were examined. Results indicate that
following both tact instructional phases, intraverbals increased for three of
four participants. Auditory imagining instruction was sufficient for two of four
participants to reach mastery criterion, and two of four participants needed some
direct instruction. Low covariation between simple intraverbal and categorization
was also observed. Functional interdependence between tacts and intraverbals and
the possible role of a conditioned hearing response are discussed.
PMID- 27606215
TI - Learning Skinner's Verbal Operants: Comparing an Online Stimulus Equivalence
Procedure to an Assigned Reading.
AB - The purpose of the present study was to compare the effects of an online stimulus
equivalence procedure to that of an assigned reading when learning Skinner's
taxonomy of verbal behavior. Twenty-six graduate students participated via an
online learning management system. One group was exposed to an online stimulus
equivalence procedure (equivalence group) that was designed to teach relations
among the names, antecedents, consequences, and examples of each elementary
verbal operant. A comparison group (reading group) read a chapter from a popular
textbook. Tests for the emergence of selection-based and topography-based
intraverbal responses were then conducted, as were tests for generalization and
maintenance. Overall, results suggest that the online equivalence procedure was
not significantly more effective in promoting topography-based responses than the
assigned reading. However, performance on selection-based tests was enhanced by
the online equivalence procedure as was performance on topography-based tests
when participants were required to provide operant names in response to
consequences or examples. On average, the equivalence group performed at a level
that was 10 percentage points (i.e., a full letter grade) above that of the
reading group. The viability of the equivalence-based procedure is discussed in
relation to the assigned reading.
PMID- 27606216
TI - A Comparison of Prompting Tactics for Teaching Intraverbals to Young Adults with
Autism.
AB - Several researchers have compared the effectiveness of tact or textual prompts to
echoic prompts for teaching intraverbal behavior to young children with autism.
We extended this line of research by comparing the effectiveness of visual
(textual or tact) prompts to echoic prompts to teach intraverbal responses to
three young adults with autism. An adapted alternating treatments design was used
with 2 to 3 comparisons for each participant. The results were mixed and did not
reveal a more effective prompting procedure across participants, suggesting that
the effectiveness of a prompting tactic may be idiosyncratic. The role of one's
learning history and the implications for practitioners teaching intraverbal
behavior to individuals with autism are discussed.
PMID- 27606217
TI - Effects of Simultaneous Script Training on Use of Varied Mand Frames by
Preschoolers with Autism.
AB - Young children with autism may fail to mand using a range of frames (e.g., "I
want," "May I have," "Please give me"). We examined the effects of simultaneous
script training and script fading on acquisition and maintenance of varied mand
frames with six preschool children with autism. For participants who did not
demonstrate increased mand variability under fixed-ratio (FR) 1 conditions, we
assessed the effects of post script-training extinction on response variability.
Following training of up to four different mand frames, three of six participants
emitted more varied mands under FR1 conditions relative to baseline. Posttraining
extinction resulted in increased mand variability for two of the three remaining
participants. Results are discussed in terms of considerations for both
establishing and ensuring the persistence of varied verbal behavior among
children with autism.
PMID- 27606218
TI - Using Textual Prompts to Teach Mands for Information Using "Who?".
AB - Recent research on teaching mands for information to children with language
deficits has focused on manipulating establishing operations (EOs). However, only
a few of those studies have programmed both EO conditions (in which information
is needed) and abolishing operation (AO) conditions (in which information has
already been provided) to ensure functional use of the mand for information.
Shillingsburg, Bowen, Valentino, and Pierce (Journal of Applied Behavior
Analysis, 47, 136-150, 2014) provided a successful demonstration of differential
responding between EO and AO conditions demonstrating control of the response by
the relevant EO. Echoic prompts resulted in successful mands for information
"Who?" One limitation of this study was that the participants did not re-issue
the initial mand upon approaching the named adult to retrieve the item. This may
be problematic in the natural environment as it is unlikely that the named adult
would know what the child was looking for. The current study sought to replicate
and expand previous research by using textual prompts to teach the mand "Who?" in
four children diagnosed with autism (Phase 1) and by requiring the mand for the
item be re-issued upon approaching the named adult (Phase 2). Textual prompts
resulted in differential use of the mand for information during EO and AO
conditions for all of the participants. Additionally, three of the four
participants who did not re-issue the mand to the named adult during the Phase 2
baseline did so following the intervention. Overall, results support the use of
textual prompts to teach mands for information to children with autism.
PMID- 27606219
TI - Emergent Intraverbal Forms may Occur as a Result of Listener Training for
Children with Autism.
AB - The purpose of the present study was to assess whether intraverbal behavior, in
the form of answers to questions, emerges as a result of listener training for
five children diagnosed with autism. Listener responses were targeted and taught
using prompting and differential reinforcement. Following successful acquisition
of listener responses, the intraverbal form of the response was probed. Data were
evaluated via a nonconcurrent multiple-baseline design that included a control
series. Results showed listener-to-intraverbal transfer for four of the five
participants. One participant required additional teaching that involved tacting
the items selected during listener training.
PMID- 27606220
TI - Derived Equivalence Relations of Geometry Skills in Students with Autism: an
Application of the PEAK-E Curriculum.
AB - The present study evaluated the efficacy of equivalence-based instruction (EBI)
as described in the PEAK-E curriculum (Dixon, 2015) for promoting the emergence
of derived geometry skills in two children with high-functioning autism. The
results suggested that direct training of shape name (A) to shape property (B)
(i.e., A-B relations) was effective for both participants. Following A-B
training, both participants demonstrated emergent relations that are consistent
with symmetry (B-A), as well as emergent shape name (A) to shape picture (C)
relations that are consistent with transitivity (A-C). The results expand on
existing literature by demonstrating the emergence of an A-C relation when
neither A nor B stimuli were ever trained to C stimuli and illustrate the
efficacy of EBI for training geometry skills.
PMID- 27606221
TI - Does Hearing About Cancer Influence Stimulus Control? An Exploratory Study of
Verbal Modulation of Stimulus Generalization.
AB - Participants first became familiar with an image showing moderate symptoms of the
skin cancer melanoma. In a generalization test, they indicated whether images
showing more and less pronounced symptoms were "like the original." Some groups
(cancer context) were told that the images depicted melanoma and that the disease
is deadly unless detected early. Control groups were not told what the images
depicted. For control groups, generalization gradients were fairly typical of
what is normally reported in the generalization literature, but for cancer
context groups, gradients were shifted such that highly symptomatic moles were
identified as "like the original" more than normal and subtly symptomatic ones
were endorsed less than normal. These results may have implications for melanoma
education efforts and, more generally, illustrate the possible importance of
studying interactions between verbal behavior and primary stimulus control.
PMID- 27606222
TI - An Annotated Bibliography of Verbal Behavior Articles Published Outside of The
Analysis of Verbal Behavior: 2015.
AB - An annotated bibliography is provided that summarizes journal articles on verbal
behavior published outside of The Analysis of Verbal Behavior in 2015, the
primary journal for scholarship in this area. Thirty such articles were
identified and annotated as a resource for practitioners, researchers, and
educators.
PMID- 27606223
TI - Accurate Delayed Matching-to-Sample Responding without Rehearsal: An
Unintentional Demonstration with Children.
AB - Research on joint control has focused on mediational responses, in which
simultaneous stimulus control from two sources leads to the emission of a single
response, such as choosing a comparison stimulus in delayed matching-to-sample.
Most recent studies of joint control examined the role of verbal mediators (i.e.,
rehearsal) in evoking accurate performance. They suggest that mediation is a
necessity for accurate delayed matching-to-sample responding. We designed an
experiment to establish covert rehearsal responses in young children. Before
participants were taught such responses; however, we observed that they responded
accurately at delays of 15 and 30 s without overt rehearsal. These findings
suggest that in some cases, rehearsal is not necessary for accurate responding in
such tasks.
PMID- 27606224
TI - Using a Verbal Analysis of Lady Gaga's Applause as a Classroom Exercise for
Teaching Verbal Behavior.
AB - Learning Skinner's (1957) verbal behavior taxonomy requires extensive study and
practice. Thus, novel classroom exercises might serve this goal. The present
manuscript describes a classroom exercise in which two students analyzed Lady
Gaga's song Applause in terms of its metaphorical arrangements. Through the
exercise, students identified various verbal operants and their subtypes,
including those seldom researched by the behavioral community (see Sautter and
LeBlanc 2006, The Analysis of Verbal Behavior, 22, 35-48), which helped them
conclude that Lady Gaga's Applause is comprised of two themes: the artist taking
control, and the artist-as-art.
PMID- 27606225
TI - Retracing Our Path.
PMID- 27606227
TI - Ask the Experts: How Can New Students Defend Behavior Analysis from
Misunderstandings?
AB - The success of behavior analysis as a field depends on the successes of its
students, researchers, practitioners, and advocates. A new generation of graduate
students will ultimately speak on the behalf of the field. In order to further
promote the field, students must not only learn about what behavior analysis is,
but also about what behavior analysis is not. We must prepare ourselves to
adequately defend behavior analysis from those who disseminate misperceptions and
misunderstandings. As such, an electronic survey designed to glean some
information on how behavior analysts would respond to various inaccuracies or
misunderstandings of behavior analysis was distributed through behavior-analytic
listservs and social media websites. Findings show that the majority of
respondents indicate that any graduate student ought to correct the
misunderstandings about the field. What do seasoned behavior analysts have to say
about the majority opinion about the responsibilities of graduate students and
what recommendations do they have for new graduate students who come across
misunderstandings about behavior analysis?
PMID- 27606226
TI - Positive Peer Reporting in the Classroom: a Review of Intervention Procedures.
AB - Positive peer reporting (PPR) is a classroom-based intervention to improve social
interactions between students using rewards and positive social attention. Along
with a variant of the procedure referred to as "Tootling," PPR has demonstrated
overwhelmingly positive results since its development. However, a unified,
standard protocol for successful implementation of PPR interventions has not yet
been established. A review of 24 studies, including 48 separately described cases
of PPR in classroom settings, provided information concerning adaptations for
students in special education, alternative school, and mainstream classrooms.
Student participants ranged from preschool (age 4) to eighth grade (age 16). This
paper summarizes the common procedural components found across cases described in
the studies. A comparison of PPR-based interventions reported in the literature
by various research teams also revealed differences in the procedures for
targeting individuals or groups, providing training and support, allocating
rewards, proceeding with daily peer report sessions, and terminating the
intervention. Variations in specific procedural elements that may relate to PPR's
effectiveness are discussed. The authors also provide suggestions to guide and
support the advancement of standardized methods of PPR for future research and
clinical application.
PMID- 27606228
TI - Ten Rules for Discussing Behavior Analysis.
AB - Mischaracterizations of behavior analysis are someone's behavior, and they should
be approached in exactly the same way that behavior analysts approach behavior
that is deemed curious, troubling, or self-injurious.
PMID- 27606229
TI - Some Useful Resources for Students Who Are Tempted to Bring Enlightenment to
Errant Non-Behaviorists.
PMID- 27606230
TI - Correspondence Training Using Special Interests to Increase Compliance During
Transitions: An Emerging Technology.
PMID- 27606231
TI - The Performance Diagnostic Checklist-Human Services: a Correction.
AB - The Performance Diagnostic Checklist (PDC) has been used in a number of
investigations to assess the environmental determinants of substandard employee
performance. Carr et al. (2013) revised the PDC to explicitly assess the
performance of employees in human-service settings who are responsible for
providing care to others: the Performance Diagnostic Checklist-Human Services
(PDC-HS). The originally published PDC-HS contained three minor scoring errors,
which have been corrected in the present version.
PMID- 27606232
TI - A Proposed Model for Selecting Measurement Procedures for the Assessment and
Treatment of Problem Behavior.
AB - Practicing behavior analysts frequently assess and treat problem behavior as part
of their ongoing job responsibilities. Effective measurement of problem behavior
is critical to success in these activities because some measures of problem
behavior provide more accurate and complete information about the behavior than
others. However, not every measurement procedure is appropriate for every problem
behavior and therapeutic circumstance. We summarize the most commonly used
measurement procedures, describe the contexts for which they are most
appropriate, and propose a clinical decision-making model for selecting
measurement produces given certain features of the behavior and constraints of
the therapeutic environment.
PMID- 27606233
TI - A Reply to the Commentaries on "School-wide PBIS: An Example of Applied Behavior
Analysis Implemented at a Scale of Social Importance" by Horner and Sugai (2015):
PBIS is Function over Form: The Clear Behavioral Roots and Opportunities the PBIS
Framework presents to the Field of Behavior Analysis Moving Forward.
AB - In the previous issue of Behavior Analysis in Practice (May 2015), a special
section of the journal was devoted to positive behavior intervention and support
(PBIS). Horner and Sugai (2015) published a manuscript providing an overview of
school-wide PBIS describing how PBIS is an example of applied behavior analysis
at a scale of social importance. A number of manuscripts providing commentary on
the Horner and Sugai manuscript were also published in this special section of
the journal. This paper will review this PBIS manuscript along with the
associated commentaries published in the May 2015 special section.
PMID- 27606234
TI - Encore.
PMID- 27606235
TI - Beginning the Dialogue on the e-Transformation: Behavior Analysis' First Massive
Open Online Course (MOOC).
AB - The e-Transformation in higher education, in which Massive Open Online Courses
(MOOCs) are playing a pivotal role, has had an impact on the modality in which
behavior analysis is taught. In this paper, we survey the history and
implications of online education including MOOCs and describe the implementation
and results for the discipline's first MOOC, delivered at Southern Illinois
University in spring 2015. Implications for the globalization and free access of
higher education are discussed, as well as the parallel between MOOCs and
Skinner's teaching machines.
PMID- 27606236
TI - Acceptance and Commitment Therapy for Individuals with Disabilities: A Behavior
Analytic Strategy for Addressing Private Events in Challenging Behavior.
AB - Applied behavior analysts work with many populations including individuals with
developmental and intellectual disabilities. Although behavior analysts have a
variety of empirically supported treatments to implement when working with
individuals with disabilities, sometimes, other variables may adversely impact
treatment effectiveness. The degree to which problematic thoughts and feelings
(private events) influence behavior may be a variable that contributes to
treatment efficacy. Traditional behavior analytic services are not always
equipped to successfully address the private events influencing client behavior.
In such cases, it may be beneficial for behavior analysts to consider additional
philosophically aligned treatments for private events. One such treatment,
acceptance and commitment therapy, may be a useful tool for behavior analysts to
incorporate into their toolbox in order to help clients. The purpose of this
paper is to introduce behavior analysts to a potential solution to the problem of
effectively addressing private events in behavior analytic services. We then
propose a model for thinking about private events in relation to clients with
disabilities and present a guide for taking steps to address private events in
the clinical setting. We conclude this paper with a call for research and present
a possible research agenda for behavior analysts.
PMID- 27606237
TI - The Effects of the Cool Versus Not Cool Procedure to Teach Social Game Play to
Individuals Diagnosed with Autism Spectrum Disorder.
AB - This study evaluated the utility of the cool versus not cool procedure for
teaching three structured indoor games to eight children diagnosed with autism
spectrum disorder (ASD). The study took place as part of a social skills group
for individuals diagnosed with ASD, and this study was one component of that
group. The cool versus not cool procedure consisted of the teacher demonstrating
each game the cool (i.e., appropriate) and not cool (i.e., inappropriate) way and
having the participants provide a rationale as to why the demonstration was
either cool or not cool. This was followed by giving the participants the
opportunity to role-play the game in front of the group. The teachers utilized
unprompted performance probes with no programmed reinforcement to create
opportunities for the participants to display the targeted behavior (s). A
multiple baseline design across behaviors and replicated across participants was
utilized. The results indicated that seven of the eight participants mastered
each of the games taught.
PMID- 27606238
TI - Using Computer Tablets to Assess Preference for Videos in Children with Autism.
AB - Using computer tablets, we assessed preference for videos in five children with
autism spectrum disorder (ASD). Then, we provided access to most preferred and
less preferred videos contingent on sitting on one of two chairs within a
concurrent schedule design. All participants spent consistently more time sitting
on the chair associated with the video selected the most often during the
preference assessment, indicating that practitioners may use the tablet-based
assessment procedure to identify potential video reinforcers for children with
ASD in applied settings.
PMID- 27606239
TI - Nice Doggie! Contact Desensitization Plus Reinforcement Decreases Dog Phobias for
Children with Autism.
AB - Dog phobias are common in individuals with autism; however, evidence supporting
behavioral interventions is limited. The current study evaluated the efficacy of
contact desensitization plus reinforcement on dog phobic behavior exhibited by
three children diagnosed with autism. The treatment package improved contact with
dogs in analog and naturalistic settings and the improvements were maintained at
follow-up and in generalization tests. Parents/caregivers also provided high
consumer satisfaction reports.Approximately 30 % of individuals diagnosed with
autism also receive a comorbid diagnosis of a clinical phobia.Research has shown
that behavioral treatment for dog phobias in individuals with intellectual
disabilities is contact desensitization plus reinforcement using two hierarchies:
size of the dog and distance to the dog; no escape extinction was necessary.The
current systematic replication shows that this treatment package was effective
for children with autism using only a single hierarchy composed of distance to
the dog.Future practitioners may wish to examine whether this treatment package
also produces changes in supplemental physiological measures such as pupil
dilation, heart rate, galvanic skin responses, and respiration.
PMID- 27606240
TI - Cumulative Instructional Time and Relative Effectiveness Conclusions: Extending
Research on Response Intervals, Learning, and Measurement Scale.
AB - Adapted alternating treatments designs were used to evaluate three computer-based
flashcard reading interventions (1-s, 3-s, or 5-s response intervals) across two
students with disabilities. When learning was plotted with cumulative
instructional sessions on the horizontal axis, the session-series graphs suggest
that the interventions were similarly effective. When the same data were plotted
as a function of cumulative instructional seconds, time-series graphs suggest
that the 1-s intervention caused the most rapid learning for one student.
Discussion focuses on applied implications of comparative effectiveness studies
and why measures of cumulative instructional time are needed to identify the most
effective intervention(s).Comparative effectiveness studies may not identify the
intervention which causes the most rapid learning.Session-series repeated
measures are not the same as time-series repeated measures.Measuring the time
students spend in each intervention (i.e., cumulative instructional seconds)
allows practitioners to identify interventions that enhance learning most
rapidly.Student time spent working under interventions is critical for drawing
applied conclusions.
PMID- 27606241
TI - A Flow Chart of Behavior Management Strategies for Families of Children with Co
Occurring Attention-Deficit Hyperactivity Disorder and Conduct Problem Behavior.
AB - Behavioral parent training is an evidence-based treatment for problem behavior
described as attention-deficit hyperactivity disorder (ADHD), oppositional
defiant disorder, and conduct disorder. However, adherence to treatment fidelity
and parent performance of the management skills remains an obstacle to optimum
outcome. One variable that may limit the effectiveness of the parent training is
that demanding behavior management procedures can be deceptively complicated and
difficult to perform. Based on outcome research for families of children with co
occurring ADHD and conduct problem behavior, an example of a visual behavior
management flow chart is presented. The flow chart may be used to help teach
specific behavior management skills to parents. The flow chart depicts a chain of
behavior management strategies taught with explanation, modeling, and role-play
with parents. The chained steps in the flow chart are elements common to well
known evidence-based behavior management strategies, and perhaps, this depiction
well serve as a setting event for other behavior analysts to create flow charts
for their own parent training, Details of the flow chart steps, as well as
examples of specific applications and program modifications conclude.
PMID- 27606242
TI - Developing the Cultural Awareness Skills of Behavior Analysts.
AB - All individuals are a part of at least one culture. These cultural contingencies
shape behavior, behavior that may or may not be acceptable or familiar to
behavior analysts from another culture. To better serve individuals, assessments
and interventions should be selected with a consideration of cultural factors,
including cultural preferences and norms. The purpose of this paper is to provide
suggestions to serve as a starting point for developing behavior analysts'
cultural awareness skills. We present strategies for understanding behavior
analysts' personal cultural values and contingencies and those of their clients,
integrating cultural awareness practices into service delivery, supervision, and
professional development, and becoming culturally aware in everyday practice.
PMID- 27606243
TI - A Comparison of the Effects of Two Prompt-Fading Strategies on Skill Acquisition
in Children with Autism Spectrum Disorders.
AB - Research has demonstrated that most-to-least (MTL) and least-to-most (LTM)
prompting are effective in helping children with Autism Spectrum Disorders
acquire a variety of new skills. However, when directly compared to one another,
the efficiency and efficacy of the prompting procedures have been variable. The
inconsistencies in the literature could be due to selecting prompt topographies
that do not promote correct responding. To address this, the present study began
by assessing different prompt topographies and then compared most-to-least (MTL)
and least-to-most (LTM) prompt-fading with only prompt topographies that were
potent enough to promote correct responding. The subsequent comparison of prompt
fading procedures revealed that MTL prompting was more effective and efficient
than LTM prompting for all three participants. Further implications for practice
and future research are discussed.
PMID- 27606244
TI - Using Video Modeling with Voiceover Instruction Plus Feedback to Train Staff to
Implement Direct Teaching Procedures.
AB - Direct teaching procedures are often an important part of early intensive
behavioral intervention for consumers with autism spectrum disorder. In the
present study, a video model with voiceover (VMVO) instruction plus feedback was
evaluated to train three staff trainees to implement a most-to-least direct (MTL)
teaching procedure. Probes for generalization were conducted with untrained
direct teaching procedures (i.e., least-to-most, prompt delay) and with an actual
consumer. The results indicated that VMVO plus feedback was effective in training
the staff trainees to implement the MTL procedure. Although additional feedback
was required for the staff trainees to show mastery of the untrained direct
teaching procedures (i.e., least-to-most and prompt delay) and with an actual
consumer, moderate to high levels of generalization were observed.
PMID- 27606245
TI - An Evaluation of a Brief Video-Based Multiple-Stimulus Without Replacement
Preference Assessment.
AB - We evaluated a brief multiple-stimulus without replacement (MSWO) preference
assessment conducted in video format with four children with autism.
Specifically, we compared the results of a video-based MSWO to the results of a
tangible MSWO. Toys identified as highly preferred (HP) in the video-based MSWO
were also HP in the tangible MSWO for three of four participants, and
correlations between video-based and tangible MSWO assessment results across
participants were strong and statistically significant. Therefore, video-based
MSWOs may be an accurate compliment to tangible MSWOs for children with autism.
PMID- 27606246
TI - Assessing Acquisition of and Preference for Mand Topographies During Functional
Communication Training.
AB - We assessed acquisition and preference for various mand topographies in the
presence of establishing operations that, historically, evoked the aggression of
a child with autism. First, we implemented functional communication training
(FCT) and reinforced picture exchange, iPad(r), or GoTalk(r) activations in a
multi-element format (noting differences in aggression and/or mand independence
across conditions). Then, we conducted a concurrent-operant mand preference
assessment. Finally, we presented assessment results to the subject's mother and
asked her to indicate her own preference. Parent and subject preferences were
aligned and we completed therapy using the iPad(r).
PMID- 27606247
TI - FCT and Delay Fading for Elopement with a Child with Autism.
AB - Nearly half of children with autism have eloped from their caregivers. In
assessing elopement, the initial functional analytic results of this case study
found positive reinforcement in the form of attention and access to tangibles
were the maintaining variables. Functional communication training (FCT) in
combination with delay fading was utilized to increase communication and decrease
elopement. Results indicated that communication was consistent, elopement
remained low, and the child learned to wait.
PMID- 27606248
TI - Teaching Feminine Hygiene Skills to Young females with Autism Spectrum Disorder
and Intellectual Disability.
AB - Little applied research focuses on teaching feminine hygiene skills to females
with disabilities, yet this is a common clinical concern. The current study
demonstrates the use of chaining to teach two young females with autism spectrum
disorder feminine hygiene skills. A nonconcurrent multiple baseline across
participants was utilized, and the results indicate that both participants
acquired the skill. Generalization probes with one participant indicated the
skill generalized to novel stimuli.
PMID- 27606249
TI - Further Manipulations in Response Effort or Magnitude of an Aversive Consequence
to Increase Self-Feeding in Children with Feeding Disorders.
AB - Although some children with feeding disorders may have the necessary skills to
feed themselves, they may lack motivation to self-feed solids and liquids. Rivas,
Piazza, Roane, Volkert, Stewart, Kadey, and Groff (Journal of Applied Behavior
Analysis, 47, 1-14, 2014) and Vaz, Volkert, and Piazza (Journal of Applied
Behavior Analysis, 44, 915-920, 2011) successfully increased self-feeding for
children who lacked motivation to self-feed by manipulating either the quantity
or the quantity and quality of bites that the therapist fed the child if he or
she did not self-feed. In the current investigation, we present three case
examples to illustrate some challenges we faced when using these procedures
outlined in the aforementioned studies and how we addressed these challenges.
PMID- 27606250
TI - Navigating a Managed Care Peer Review: Guidance for Clinicians Using Applied
Behavior Analysis in the Treatment of Children on the Autism Spectrum.
AB - As autism rates increase, providers of applied behavioral analysis (ABA) services
are more frequently engaging with managed care companies to discuss the medical
necessity of treatment. In an effort to maximize the efficiency and effectiveness
of these reviews, we draw upon our experience as peer reviewers for a managed
care company to guide ABA providers in discussions with managed care on behalf of
their patients. In this article, we first provide an overview of the managed care
peer review process. We then discuss the elements of medical necessity that
managed care companies ask about during the review process. Finally, we review
specific strategies that ABA providers can use during the process to optimize
authorizations for payment for services. Throughout the paper, we provide sample
dialogues between providers and peer reviewers based on our experience working
for a managed care company along with specific recommendations that we hope will
ensure a more collegial and effective peer review process for all involved.
PMID- 27606251
TI - The Practical Importance of the Distinction Between Open and Closed-Ended
Indirect Assessments.
AB - The identification of functional relations is a hallmark of applied behavior
analysis. Building upon this foundation, applied behavior analysts have developed
and researched a number of practices that fall within the purview of Functional
Behavioral Assessment, a framework used to understand factors that influence a
target behavior. Indeed, there now exists a wide range of procedures that fall
within the purview of Functional Behavioral Assessment, with different procedures
being associated with different strengths and limitations. Indirect assessments
are commonly featured in most descriptions of the Functional Behavioral
Assessment process. This paper focuses on the distinction between open and closed
ended indirect assessments specifically, highlighting their strengths and
limitations. After distinguishing between these two types of indirect assessments
considerations for practice are provided.
PMID- 27606252
TI - Social Thinking(r): Science, Pseudoscience, or Antiscience?
AB - Today, there are several interventions that can be implemented with individuals
diagnosed with autism spectrum disorder. Most of these interventions have limited
to no empirical evidence demonstrating their effectiveness, yet they are widely
implemented in home, school, university, and community settings. In 1996, Green
wrote a chapter in which she outlined three levels of science: evidence science,
pseudoscience, and antiscience; professionals were encouraged to implement and
recommend only those procedures that would be considered evidence science. Today,
an intervention that is commonly implemented with individuals diagnosed with
autism spectrum disorder is Social Thinking(r). This intervention has been
utilized by behaviorists and non-behaviorists. This commentary will outline
Social Thinking(r) and provide evidence that the procedure, at the current time,
qualifies as a pseudoscience and, therefore, should not be implemented with
individuals diagnosed with autism spectrum disorder, especially given the
availability of alternatives which clearly meet the standard of evidence science.
PMID- 27606253
TI - Effects of Response Effort on Resurgence.
AB - The present study examined response effort during resurgence tests. Six children
were trained to place balls in baskets that were placed either close (.0254 m) or
far away (1.829 m or .9 m). Resurgence was assessed using a linear strip design,
where responses were reinforced on a variable-interval 10-s schedule or put on
extinction. During resurgence tests, minimal to low rates of resurgence
associated with the greater response effort (i.e., placing a ball in the basket
further way) were observed across all six participants, regardless of distance.
PMID- 27606254
TI - Evaluating Components of Behavior-Analytic Training Programs.
AB - This study investigates the consistency of behavior-analytic training with the
Behavior Analysis Certification Board's task list. A survey about the content of
behavior-analytic training programs was sent to Behavior Analyst Certification
Board (BACB)-approved training program directors. There were many program
directors that felt particular areas do not have sufficient coverage (e.g.,
Behavioral Pharmacology, Biological Bases of Behavior, Organizational Behavior
Management), and several program directors reported that their course sequence
does not adequately prepare students in basic research. Results suggest that the
evaluation of behavior-analytic training content may be warranted.
PMID- 27606255
TI - Study on the Behavior of Dengue Viruses during Outbreaks with Reference to
Entomological and Laboratory Surveillance in the Cuddalore, Nagapattinam, and
Tirunelveli Districts of Tamil Nadu, India.
AB - OBJECTIVES: This study was carried out in order to understand the behavior of
dengue viruses through the entomological and laboratory surveillance of
outbreaks. The aim of the study was to provide additional research to support
current knowledge of epidemiological, clinical, and laboratory diagnosis of
dengue virus and ultimately to use this information to forecast dengue as well as
to justify intervention measures. METHODS: Data on the presence of Aedes larvae
in human dwellings during the entomological surveillance in Cuddalore,
Nagapattinam, and Tirunelveli dengue outbreaks were taken to compute indices,
namely the House Index (HI), Container index (CI), and the Breteau Index (BI).
Standard procedures were followed for nonstructural Protein 1 (NS1) and
immunoglobulin M enzyme linked immunosorbent assay for the confirmation of
dengue. Serovar confirmation was made in the Kottayam field station of the Vector
Control Research Center, Puducherry. RESULTS: Larval indices HI < 2-3% and BI <
20 contributed to halting the outbreak. Incubation of the dengue viruses in
humans was detected at 15 days, NS1 was identified as a tool for the early
diagnosis of dengue cases and its presence indicated the need to implement all
available interventions. It was also discovered that it is helpful to search for
hidden habitats of Aedes when dengue cases have not been reduced even after the
sustainable management of the larval indices, HI < 5% and BI < 20. Based on the
observed incidences of stopping dengue outbreaks, it was learnt that neighborhood
areas of the outbreak villages, around 400 m, should have permissible larval
indices < 5% HI and BI < 20. Heterogeneous serovars that led to dengue
hemorrhagic fever and Dengue Shock Syndrome (DSS) were identified using reverse
transcription polymerase chain reaction and reconfirmed in the field as DEN-1 and
DEN-3 viruses and were circulating in Tirunelveli during the outbreak.
CONCLUSION: The behaviors of dengue viruses experienced in experimental,
clinical, epidemiological, entomological, and laboratory surveillance did not
deviate from observations in the field during dengue outbreaks in the Cuddalore,
Nagapattinam, and Tirunelveli districts of Tamil Nadu, India.
PMID- 27606256
TI - Pharmaceutical product development: A quality by design approach.
AB - The application of quality by design (QbD) in pharmaceutical product development
is now a thrust area for the regulatory authorities and the pharmaceutical
industry. International Conference on Harmonization and United States Food and
Drug Administration (USFDA) emphasized the principles and applications of QbD in
pharmaceutical development in their guidance for the industry. QbD attributes are
addressed in question-based review, developed by USFDA for chemistry,
manufacturing, and controls section of abbreviated new drug applications. QbD
principles, when implemented, lead to a successful product development,
subsequent prompt regulatory approval, reduce exhaustive validation burden, and
significantly reduce post-approval changes. The key elements of QbD viz., target
product quality profile, critical quality attributes, risk assessments, design
space, control strategy, product lifecycle management, and continual improvement
are discussed to understand the performance of dosage forms within design space.
Design of experiments, risk assessment tools, and process analytical technology
are also discussed for their role in QbD. This review underlines the importance
of QbD in inculcating science-based approach in pharmaceutical product
development.
PMID- 27606257
TI - Improved dissolution and anti-inflammatory activity of ibuprofen-polyethylene
glycol 8000 solid dispersion systems.
AB - BACKGROUND: The purpose of this study was to develop ibuprofen (IB)-polyethylene
glycol (PEG) 8000 solid dispersions (SDs) and investigate them for in vitro
dissolution and in vivo anti-inflammatory activity. MATERIALS AND METHODS: IB-PEG
8000 SDs were prepared by fusion method using varying combination ratios of IB
and PEG 8000. Characterization based on surface morphology, particle size,
absolute drug content, and Fourier transform infrared (FT-IR) spectroscopy was
carried out on the SDs. The in vitro release of IB from the SDs was performed in
simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH
7.4) without enzymes, whereas the anti-inflammatory activity was evaluated using
egg albumin-induced rat paw edema model. RESULTS: Greenish brown, discrete, and
irregularly shaped SDs of mean particle size range 113.5 +/- 2.5-252.5 +/- 1.9
MUm, which were stable over 3 months, were obtained. The drug content of the SDs
ranged from 73.4 +/- 2.9 % to 83.5 +/- 2.7%. Although the drug content increased
with increased concentration of PEG 8000 in the SDs, the mean particle size
decreased with increased concentration of PEG 8000 in the SDs. The FT-IR results
indicate no strong chemical interaction of IB and PEG 8000 in the SDs. There was
marked increase in the dissolution rate of IB from the SDs (P < 0.05) as compared
to pure IB and physical mixture. The dissolution was better in SIF than in SGF.
The increased dissolution rate of IB may be due to the formation of
microcrystals, increased wettability and dispersibility in PEG 8000. The SDs
showed good anti-inflammatory properties achieving up to 90% edema inhibition at
6 h while the pure sample of IB had 77% edema inhibition at 6 h. CONCLUSION: SDs
based on IB-PEG 8000 is a good approach to enhance the dissolution rate and anti
inflammatory activity of IB, thus, encouraging further development of the SDs.
PMID- 27606260
TI - Preparation, characterization, and in vivo evaluation of valsartan porous
matrices using emulsion solvent evaporation technique.
AB - INTRODUCTION: Valsartan is a type II Biopharmaceutics Classification System (BCS)
classified drug. The poor aqueous solubility restricts its use in developing
sustained or controlled release systems for the treatment of chronic hypertensive
conditions. The present investigation was conducted with an objective to
formulate porous matrices (PMs) of valsartan in order to enhance aqueous
solubility. MATERIALS AND METHODS: Polyvinylpyrrolidone (PVP) K30 and poloxamer
407 were used as hydrophilic carriers; hexane was used as a pore-forming agent,
ethanol was used as a solvent, and tween 20 was used as an emulgent. The prepared
porous matrices were characterized and based on the maximum slope obtained from
the Washburn method and other characterization results; the drug PVP K30 (1:1.5)
was selected and further evaluated in vivo by the rat gut method. RESULTS: The
prepared porous matrices are white, free-flowing powders. Among prepared
formulations drug PVP K30 (1:1.5) showed maximum Washburn slope of 0.0103. The
mean particle size was found to be 0.82 MU and D50 (median) value was found to be
0.55 MU. The scanning of particles at various magnifications by scanning electron
microscopy (SEM) analysis revealed that the method had effectively induced
porosity. The Q value of valsartan from porous matrices was observed at 20 min
with a first order regression value of 0.917. The calculated difference factor
(F1) when compared with pure valsartan was observed to be 63.32%. From the values
obtained, it was evident that the method amplifies the percentage of drug
dissolution between sixfold and eightfold when compared to pure drug. From the
absorption studies by the rat gut method, the absorption of porous matrices
increased threefold. CONCLUSION: Porous matrices of valsartan: PVP K30 (1:1.5
ratio) hold promise for the enhancement of solubility and consecutive formulation
of controlled release systems even with poorly soluble drugs.
PMID- 27606258
TI - Preparation and evaluation of a novel oral delivery system for low molecular
weight heparin.
AB - OBJECTIVE: The objective of the present work was to prepare and evaluate a novel
oral formulation for systemic delivery of low molecular weight heparin (LMWH).
The formulation consisted of Eudragit S 100-coated positively charged liposomes
encapsulating LMWH and a penetration enhancer. MATERIALS AND METHODS: Positively
charged liposomes were first prepared by the thin film hydration method using
lipid (soy phosphotidylcholine and cholesterol) and stearyl amine (SA) in the
optimum ratio of 16:1, along with cetylpyridinium chloride (CPC) as a penetration
enhancer. Prepared liposomes were coated with negatively charged Eudragit S 100
(0.3% w/v). The formulations were studied for various in vitro and in vivo
properties. Differential scanning calorimetry (DSC), x-ray diffraction (XRD),
scanning electron microscopy (SEM), Fourier transform infrared spectroscopy
(FTIR) studies, and in vitro drug release were used for in vitro characterization
of the formulations. Ex vivo permeation studies were performed by using distal
small intestine of rat. Oral absorption studies were conducted with the rat
model. RESULTS: Coating of the liposomes was confirmed by SEM and particle size
determination studies. In vitro release studies of coated liposomes have
demonstrated that the release of LMWH was in the following order: Stomach < small
intestine < distal small intestine < colon. Ex vivo permeation studies have shown
a fivefold increase in permeation of LMWH with Eudragit S 100-coated liposomes
compared to uncoated, uncharged liposomes. Oral absorption studies have showed
that with Eudragit-coated liposomes, the oral bioavailability of LMWH was
improved, compared to plain LMWH solution. This is revealed by a threefold
increase in the area under the curve (AUC) of the plasma concentration time
curve. CONCLUSION: A novel formulation for oral delivery of LMWH was thus
successfully prepared and evaluated.
PMID- 27606259
TI - Development and characterization of novel hydrogel containing antimicrobial drug
for treatment of burns.
AB - INTRODUCTION: The aim of burn management and therapy is fast healing and
epithelisation to prevent infection. The present study is concerned with the
development and characterization of a novel nanaoparticulate system; cubosomes,
loaded with silver sulfadiazine (SSD) and Aloe vera for topical treatment of
infected burns. METHODS: Cubosome dispersions were formulated by an
emulsification technique using different concentrations of a lipid phase Glyceryl
Monooleate (GMO) and Poloxamer 407. The optimum formulae were incorporated in an
aloe vera gel containing carbopol 934, to form cubosomal hydrogels (cubogels).
The cubogels were characterized by in vitro release of SSD, rheological
properties, pH, bioadhesion, Transmission Electron Microscopy and in-vivo Wound
Healing Study. RESULTS: The results show that the different concentration of GMO
had significant effect on particle size, % EE and in vitro drug release. From the
in-vitro drug release pattern and similarity factor (f2), it was concluded that
batch CG3 (15% GMO and 1% P407) exhibited complete and controlled drug release
within 12 hour (i.e. 98.25%), better bio adhesion and superior burn healing as
compared to the marketed product. CONCLUSION: The in vivo burns healing study in
rats revealed that the prepared optimized cubogel containing SSD and aloe vera
has superior burns healing rate than cubogel with only SSD and marketed
preparation so, it may be successfully used in the treatment of deep second
degree burn.
PMID- 27606262
TI - Validation of Attitude and Heading Reference System and Microsoft Kinect for
Continuous Measurement of Cervical Range of Motion Compared to the Optical Motion
Capture System.
AB - OBJECTIVE: To compare optical motion capture system (MoCap), attitude and heading
reference system (AHRS) sensor, and Microsoft Kinect for the continuous
measurement of cervical range of motion (ROM). METHODS: Fifteen healthy adult
subjects were asked to sit in front of the Kinect camera with optical markers and
AHRS sensors attached to the body in a room equipped with optical motion capture
camera. Subjects were instructed to independently perform axial rotation followed
by flexion/extension and lateral bending. Each movement was repeated 5 times
while being measured simultaneously with 3 devices. Using the MoCap system as the
gold standard, the validity of AHRS and Kinect for measurement of cervical ROM
was assessed by calculating correlation coefficient and Bland-Altman plot with
95% limits of agreement (LoA). RESULTS: MoCap and ARHS showed fair agreement (95%
LoA<10 degrees ), while MoCap and Kinect showed less favorable agreement (95%
LoA>10 degrees ) for measuring ROM in all directions. Intraclass correlation
coefficient (ICC) values between MoCap and AHRS in -40 degrees to 40 degrees
range were excellent for flexion/extension and lateral bending (ICC>0.9). ICC
values were also fair for axial rotation (ICC>0.8). ICC values between MoCap and
Kinect system in -40 degrees to 40 degrees range were fair for all motions.
CONCLUSION: Our study showed feasibility of using AHRS to measure cervical ROM
during continuous motion with an acceptable range of error. AHRS and Kinect
system can also be used for continuous monitoring of flexion/extension and
lateral bending in ordinary range.
PMID- 27606261
TI - The Modulation of Neurotrophin and Epigenetic Regulators: Implication for
Astrocyte Proliferation and Neuronal Cell Apoptosis After Spinal Cord Injury.
AB - OBJECTIVE: To investigate alterations in the expression of the main regulators of
neuronal survival and death related to astrocytes and neuronal cells in the brain
in a mouse model of spinal cord injury (SCI). METHODS: Eight-week-old male
imprinting control region mice (n=36; 30-35 g) were used in this study and
randomly assigned to two groups: the naive control group (n=18) and SCI group
(n=18). The mice in both groups were randomly allocated to the following three
time points: 3 days, 1 week, and 2 weeks (n=6 each). The expression levels of
regulators such as brain-derived neurotrophic factor (BDNF), glial cell line
derived neurotrophic factor (GDNF), nerve growth factor (NGF), histone
deacetylase 1 (HDAC1), and methyl-CpG-binding protein 2 (MeCP 2) in the brain
were evaluated following thoracic contusive SCI. In addition, the number of
neuronal cells in the motor cortex (M1 and M2 areas) and the number of astrocytes
in the hippocampus were determined by immunohistochemistry. RESULTS: BDNF
expression was significantly elevated at 2 weeks after injury (p=0.024). The GDNF
level was significantly elevated at 3 days (p=0.042). The expression of HDAC1 was
significantly elevated at 1 week (p=0.026). Following SCI, compared with the
control the number of NeuN-positive cells in the M1 and M2 areas gradually and
consistently decreased at 2 weeks after injury. In contrast, the number of
astrocytes was significantly increased at 1 week (p=0.029). CONCLUSION: These
results demonstrate that the upregulation of BDNF, GDNF and HDAC1 might play on
important role in brain reorganization after SCI.
PMID- 27606263
TI - Phantom Study of a New Laser-Etched Needle for Improving Visibility During
Ultrasonography-Guided Lumbar Medial Branch Access With Novices.
AB - OBJECTIVE: To compare the visibility and procedural parameters between a standard
spinal needle and a new laser-etched needle (LEN) in real-time ultrasonography
guided lumbar medial branch access in a phantom of the lumbosacral spine.
METHODS: We conducted a prospective single-blinded observational study at a
rehabilitation medicine center. A new model of LEN was manufactured with a
standard 22-gauge spinal needle and a laser etching machine. Thirty-two
inexperienced polyclinic medical students performed ultrasonography-guided lumbar
medial branch access using both a standard spinal needle and a LEN with scanning
protocol. The outcomes included needle visibility score, needle elapsed time,
first-pass success rate, and number of needle sticks. RESULTS: The LEN received
significantly better visibility scores and shorter needle elapsed time compared
to the standard spinal needle. First-pass success rate and the number of needle
sticks were not significantly different between needles. CONCLUSION: A new LEN is
expected to offer better visibility and enable inexperienced users to perform an
ultrasonography-guided lumbar medial branch block more quickly. However, further
study of variables may be necessary for clinical application.
PMID- 27606264
TI - Combined Effect of Bilateral Ovariectomy and Anterior Cruciate Ligament
Transection With Medial Meniscectomy on the Development of Osteoarthritis Model.
AB - OBJECTIVE: To investigate the combined effect of bilateral ovariectomy (OVX) and
anterior cruciate ligament transection (ACLT) with medial meniscectomy (MM) on
the development of osteoarthritis (OA). METHODS: Twenty female 15-week-old
Sprague-Dawley rats were used. Five rats in each group underwent bilateral OVX
(OVX group), bilateral ACLT with MM (ACLT with MM group), bilateral OVX plus ACLT
with MM (OVX plus ACLT with MM group), and sham surgery (SHAM group). All the
rats were subjected to treadmill running for 4 weeks. The behavioral evaluation
for induction of OA used the number of rears method, and this was conducted at 1,
2, and 4 weeks post-surgery. Bone mineral density (BMD) was calculated with micro
computerized tomography images and the modified Mankin's scoring was used for the
histological changes. RESULTS: The number of rears in the OVX plus ACLT with MM
group decreased gradually and more rapidly in the ACLT with MM group.
Histologically, the OVX plus ACLT with MM group had a significantly higher
modified Mankin's score than the OVX group (p=0.008) and the SHAM group
(p=0.008). BMDs of the OVX plus ACLT with MM group were significantly lower than
the SHAM group (p=0.002), and the ACLT with MM group (p=0.003). CONCLUSION: We
found that bilateral OVX plus ACLT with MM induced definite OA change in terms of
histology and BMD compared to bilateral OVX and ACLT with MM alone. Therefore,
OVX and ACLT with MM was an appropriate degenerative OA rat model.
PMID- 27606265
TI - Botulinum Toxin A Injection into the Subscapularis Muscle to Treat Intractable
Hemiplegic Shoulder Pain.
AB - OBJECTIVE: To evaluate the beneficial effect of botulinum toxin A (Botox)
injection into the subscapularis muscle on intractable hemiplegic shoulder pain.
METHODS: Six stroke patients with intractable hemiplegic shoulder pain were
included. Botulinum toxin A was injected into the subscapularis muscle.
Intractable hemiplegic shoulder pain was evaluated using an 11-point numerical
rating scale. Pain-free range of motion was assessed for shoulder abduction and
external rotation. The spasticity of the shoulder internal rotator was measured
using the modified Ashworth scale. Assessments were carried out at baseline and
at 1, 2, 4, and, if possible, 8 weeks. RESULTS: Intractable hemiplegic shoulder
pain was improved (p=0.004) after botulinum toxin injection into the
subscapularis muscle. Restricted shoulder abduction (p=0.003), external rotation
(p=0.005), and spasticity of the shoulder internal rotator (p=0.005) were also
improved. Improved hemiplegic shoulder pain was correlated with improved shoulder
abduction (r=-1.0, p<0.001), external rotation (r=-1.0, p<0.001), and spasticity
of the internal rotator (r=1.0, p<0.001). CONCLUSION: Botulinum toxin A injection
into the subscapularis muscle appears to be valuable in the management of
intractable hemiplegic shoulder pain.
PMID- 27606266
TI - Effect of Laryngopharyngeal Neuromuscular Electrical Stimulation on Dysphonia
Accompanied by Dysphagia in Post-stroke and Traumatic Brain Injury Patients: A
Pilot Study.
AB - OBJECTIVE: To investigate the effect of laryngopharyngeal neuromuscular
electrical stimulation (NMES) on dysphonia in patients with dysphagia caused by
stroke or traumatic brain injury (TBI). METHODS: Eighteen patients participated
in this study. The subjects were divided into NMES (n=12) and conventional
swallowing training only (CST, n=6) groups. The NMES group received NMES combined
with CST for 2 weeks, followed by CST without NMES for the next 2 weeks. The CST
group received only CST for 4 weeks. All of the patients were evaluated before
and at 2 and 4 weeks into the study. The outcome measurements included
perceptual, acoustic and aerodynamic analyses. The correlation between dysphonia
and swallowing function was also investigated. RESULTS: There were significant
differences in the GRBAS (grade, roughness, breathiness, asthenia and strain
scale) total score and sound pressure level (SPL) between the two groups over
time. The NMES relative to the CST group showed significant improvements in total
GRBAS score and SPL at 2 weeks, though no inter-group differences were evident at
4 weeks. The improvement of the total GRBAS scores at 2 weeks was positively
correlated with the improved pharyngeal phase scores on the functional dysphagia
scale at 2 weeks. CONCLUSION: The results demonstrate that laryngopharyngeal NMES
in post-stroke or TBI patients with dysphonia can have promising effects on
phonation. Therefore, laryngopharyngeal NMES may be considered as an additional
treatment option for dysphonia accompanied by dysphagia after stroke or TBI.
PMID- 27606267
TI - The Effect of an Upper Limb Rehabilitation Robot on Hemispatial Neglect in Stroke
Patients.
AB - OBJECTIVE: To investigate the effectiveness of an upper limb rehabilitation robot
therapy on hemispatial neglect in stroke patients. METHODS: Patients were
randomly divided into an upper limb rehabilitation robot treatment group (robot
group) and a control group. The patients in the robot group received left upper
limb training using an upper limb rehabilitation robot. The patients sat on the
right side of the robot, so that the monitor of the robot was located on the
patients' left side. In this position, patients could focus continuously on the
left side. The control group received conventional neglect treatment, such as
visual scanning training and range of motion exercises, administered by
occupational therapists. Both groups received their respective therapies for 30
minutes a day, 5 days a week for 3 weeks. Several tests were used to evaluate
treatment effects before and after the 3-week treatment. RESULTS: In total, 38
patients (20 in the robot group and 18 in the control group) completed the study.
After completion of the treatment sessions, both groups showed significant
improvements in the Motor-Free Visual Perception Test 3rd edition (MVPT-3), the
line bisection test, the star cancellation test, the Albert's test, the Catherine
Bergego scale, the Mini-Mental State Examination and the Korean version of
Modified Barthel Index. The changes in all measurements showed no significant
differences between the two groups. CONCLUSION: This present study showed that
the upper limb robot treatment had benefits for hemispatial neglect in stroke
patients that were similar to conventional neglect treatment. The upper limb
robot treatment could be a therapeutic option in the treatment of hemispatial
neglect after stroke.
PMID- 27606268
TI - The Relationship Between Tongue Pressure and Oral Dysphagia in Stroke Patients.
AB - OBJECTIVE: To evaluate the relationships between tongue pressure and different
aspects of the oral-phase swallowing function. METHODS: We included 96 stroke
patients with dysphagia, ranging in age from 40 to 88 years (mean, 63.7 years).
Measurements of tongue pressure were obtained with the Iowa Oral Performance
Instrument, a device with established normative data. Three trials of maximum
performance were performed for lip closure pressure (LP), anterior hard palate-to
tongue pressure (AP), and posterior hard palate-to-tongue pressure (PP); buccal
to-tongue pressures on both sides were also recorded (buccal-to-tongue pressure,
on the weak side [BW]; buccal-to-tongue pressure, on the healthy side [BH]). The
average pressure in each result was compared between the groups. Clinical
evaluation of the swallowing function was performed with a videofluoroscopic
swallowing study. RESULTS: The average maximum AP and PP values in the intact LC
group were significantly higher than those in the inadequate lip closure group
(AP, p=0.003; PP, p<0.001). AP and PP showed significant relationships with bolus
formation (BF), mastication, premature bolus loss (PBL), tongue to palate contact
(TP), and oral transit time (OTT). Furthermore, LP, BW, and BH values were
significantly higher in the groups with intact mastication, without PBL and
intact TP. CONCLUSION: These findings indicate that the tongue pressure appears
to be closely related to the oral-phase swallowing function in post-stroke
patients, especially BF, mastication, PBL, TP and OTT.
PMID- 27606269
TI - Efficacy of Mirror Therapy Containing Functional Tasks in Poststroke Patients.
AB - OBJECTIVE: To investigate the effect of mirror therapy containing functional
tasks on upper extremity function and activities of daily living in patients with
subacute stroke. METHODS: The subjects were randomly divided into two groups: the
mirror therapy group (30 patients) and the sham therapy group (30 patients). The
mirror therapy group underwent a mirror therapy program together with
conventional therapy for 20 minutes per day on 5 days per week for 4 weeks. The
control group received a sham conventional therapy program under the same
schedule as the mirror therapy group. The Fugl-Meyer Motor Function Assessment
(FMA), Brunnstrom motor recovery stage, and Modified Barthel Index (MBI) were
evaluated 4 weeks after the treatment. RESULTS: The upper extremity function on
the affected side and ability to perform daily life activities after the
intervention were significantly improved in both groups. After 4 weeks of
intervention, improvements in the FMA (p=0.027) and MBI (p=0.041) were
significantly greater in the mirror therapy group than the sham therapy group.
CONCLUSION: In this study, we found that the mirror therapy containing functional
task was effective in terms of improving the upper extremity functions and
activities of daily living in patients with subacute stroke.
PMID- 27606270
TI - Association of Dysphagia With Supratentorial Lesions in Patients With Middle
Cerebral Artery Stroke.
AB - OBJECTIVE: To determine the supratentorial area associated with poststroke
dysphagia, we assessed the diffusion tensor images (DTI) in subacute stroke
patients with supratentorial lesions. METHODS: We included 31 patients with a
first episode of infarction in the middle cerebral artery territory. Each subject
underwent brain DTI as well as a videofluoroscopic swallowing study (VFSS) and
patients divided were into the dysphagia and non-dysphagia groups. Clinical
dysphagia scale (CDS) scores were compared between the two groups. The
corticospinal tract volume (TV), fractional anisotropy (FA) and apparent
diffusion coefficient (ADC) values were calculated for 11 regions of interest in
the supratentorial area-primary motor cortex, primary somatosensory cortex,
supplementary motor cortex, anterior cingulate cortex, orbitofrontal cortex,
parieto-occipital cortex, insular cortex, posterior limb of the internal capsule,
thalamus, and basal ganglia (putamen and caudate nucleus). DTI parameters were
compared between the two groups. RESULTS: Among the 31 subjects, 17 were
diagnosed with dysphagia by VFSS. Mean TVs were similar across the two groups.
Significant inter-group differences were observed in two DTI values: the FA value
in the contra-lesional primary motor cortex and the ADC value in the bilateral
posterior limbs of the internal capsule (all p<0.05). CONCLUSION: The FA value in
the primary motor cortex on the contra-lesional side and the ADC value in the
bilateral PLIC can be associated with dysphagia in middle cerebral artery stroke.
PMID- 27606271
TI - The Effect of Cardiac Rehabilitation Exercise Training on Cardiopulmonary
Function in Ischemic Cardiomyopathy With Reduced Left Ventricular Ejection
Fraction.
AB - OBJECTIVE: To observe the effect and safety of cardiac rehabilitation (CR)
exercise in ischemic cardiomyopathy and to compare the results between patients
with preserved left ventricular ejection fraction (LVEF) and reduced LVEF.
METHODS: Patients with ischemic cardiomyopathy with LVEF <50% were included as
subjects. The patients were classified into the preserved LVEF (pLVEF; LVEF 41%
49%) group and the reduced LVEF (rLVEF; LVEF <=40%) group. Patients underwent
hourly aerobic exercise training sessions with an intensity of 60%-85% of heart
rate reserve, three times a week for 6 weeks. Graded exercise test and
transthoracic echocardiogram were performed in all study patients before and
after completion of the CR exercise program. RESULTS: After completion of the CR
exercise program, both groups (pLVEF, n=30; rLVEF, n=18) showed significant
increases in LVEF and VO2max. In the pLVEF group, LVEF and VO2max increased from
45.1%+/-4.8% to 52.5%+/-9.6% (p<0.001) and from 24.1+/-6.3 to 28.1+/-8.8
mL/kg/min (p=0.002), respectively. In the rLVEF group, LVEF and VO2max increased
from 29.7%+/-7.7% to 37.6%+/-10.3% (p<0.001) and from 17.6+/-4.7 to 21.2+/-5.1
mL/kg/min (p<0.001), respectively. Both groups completed their exercise program
safely. CONCLUSION: In both groups, patients with ischemic cardiomyopathy who
completed a 6-week supervised CR exercise program demonstrated remarkable
improvements in cardiopulmonary function. This result implies that neither of the
two groups showed higher efficacy in comparison to each other, but we can
conclude that CR exercise in the rLVEF group was as effective and safe as that in
the pLVEF group.
PMID- 27606272
TI - Longitudinal Trends in Fall Accidents in Community Dwelling Korean Adults: The
2008-2013 Korean Community Health Survey.
AB - OBJECTIVE: To describe the longitudinal characteristics of unintentional fall
accidents using a representative population-based sample of Korean adults.
METHODS: We examined data from the Korean Community Health Survey from 2008 to
2013. Univariate analysis and multivariable logistic regression were used to
identify the characteristics of fall accidents in adults. RESULTS: Between 2008
and 2013, the incidence rate of fall accidents requiring medical treatment
increased from 1,248 to 3,423 per 100,000 people (p<0.001), while the proportion
of indoor fall accidents decreased from 38.12% to 23.16% (p<0.001). Females had
more annual fall accidents than males (p<0.001). The major reason for fall
accidents was slippery floors (33.7% in 2011 and 36.3% in 2013). Between 2008 and
2010, variables associated with higher fall accident risk included specific
months (August and September), old age, female gender, current drinker, current
smoker, diabetes, osteoarthritis, osteoporosis, and depression. A high level of
education and living with a partner were negatively associated with fall accident
risk. In 2013, people experiencing more than 1 fall accident felt more fear of
falling than those having no fall accidents (odds ratio [OR] for 1 fall, 2.12;
95% confidence interval [CI], 2.04-2.12; OR for more than 2 falls, 2.97; 95% CI,
2.83-3.10). CONCLUSION: The occurrence of fall accidents has consistently
increased in Korea from 2008 to 2013. Future intervention studies are needed to
reduce the increasing incidence rates of fall accidents in community dwelling
adults.
PMID- 27606273
TI - Prediction of Ambulatory Status After Hip Fracture Surgery in Patients Over 60
Years Old.
AB - OBJECTIVE: To predict ambulatory capacity, 1 month after physical therapy
following hip fracture surgery. METHODS: A retrospective chart review was carried
out. Patients more than 60 years old, who underwent hip fracture surgery and
received physical therapies, were selected (n=548). Age, gender, presence of
cognitive dysfunction, combined medical diseases, combined fractures, previous
history of hip surgery, prefracture ambulatory capacity, days from the fracture
to surgery, type of fracture, type of surgery, presence of postoperative
complications, days from the surgery to physical therapy, and total admission
period, were collected. Prefracture ambulatory capacity and postoperative
ambulatory capacity were classified into non-ambulatory status (NA), ambulation
with assistive device (AA), and independent-ambulation without any assistive
device (IA). Multiple-logistic regression analysis was performed for the
prediction of postoperative ambulatory capacity. RESULTS: Age (odds ratio
[OR]=0.94 for IA and 0.96 for IA or AA), gender (OR=1.64 for IA and 0.98 for IA
or AA), prefracture ambulatory capacity (OR of IA=19.17 for IA; OR of IA=16.72
for IA or AA; OR of AA=1.26 for IA, OR of AA=9.46 for IA or AA), and combined
medical disease (OR=2.02) were found to be the factors related to postoperative
ambulatory capacity and the prediction model was set up using these four factors.
CONCLUSION: Using this model, we can predict the ambulatory capacity following
hip fracture surgery. Further prospective studies should be constructed to
improve postoperative ambulatory capacity.
PMID- 27606274
TI - Length of Hospital Stay After Stroke: A Korean Nationwide Study.
AB - OBJECTIVE: To investigate the length of hospital stay (LOS) after stroke using
the database of the Korean Health Insurance Review & Assessment Service. METHODS:
We matched the data of patients admitted for ischemic stroke onset within 7 days
in the Departments of Neurology of 12 hospitals to the data from the database of
the Korean Health Insurance Review & Assessment Service. We recruited 3,839
patients who were hospitalized between January 2011 and December 2011, had a
previous modified Rankin Scale of 0, and no acute hospital readmission after
discharge. The patients were divided according to the initial National Institute
of Health Stroke Scale score (mild, <=5; moderate, >5 and <=13; severe, >13); we
compared the number of hospitals that admitted patients and LOS after stroke
according to severity, age, and sex. RESULTS: The mean LOS was 115.6+/-219.0 days
(median, 19.4 days) and the mean number of hospitals was 3.3+/-2.1 (median, 2.0).
LOS was longer in patients with severe stroke (mild, 65.1+/-146.7 days; moderate,
223.1+/-286.0 days; and severe, 313.2+/-336.8 days). The number of admitting
hospitals was greater for severe stroke (mild, 2.9+/-1.7; moderate, 4.3+/-2.6;
and severe, 4.5+/-2.4). LOS was longer in women and shorter in patients less than
65 years of age. CONCLUSION: LOS after stroke differed according to the stroke
severity, sex, and age. These results will be useful in determining the
appropriate LOS after stroke in the Korean medical system.
PMID- 27606275
TI - Static and Dynamic Parameters in Patients With Degenerative Flat Back and Change
After Corrective Fusion Surgery.
AB - OBJECTIVE: To evaluate characteristics of static and dynamic parameters in
patients with degenerative flat back (DFB) and to compare degree of their
improvement between successful and unsuccessful surgical outcome groups. METHODS:
Forty-seven patients with DFB were included who took whole spine X-ray and three
dimensional motion analysis before and 6 months after corrective surgery. Forty
four subjects were selected as a control group. As static parameters, thoracic
kyphosis (TK), thoracolumbar junction (TLJ), lumbar lordosis (LL), pelvic
incidence (PI), sacral slope (SS), and pelvic tilt (PT) were measured. As dynamic
parameters, maximal and minimal angle of pelvic tilt, lower limb joints, and
thoracic and lumbar vertebrae column (dynamic TK and LL) in sagittal plane were
obtained. RESULTS: The DFB group showed smaller TK and larger LL, pelvic
posterior tilt, hip flexion, knee flexion, and ankle dorsiflexion than the
control group. Most of these parameters were significantly corrected by fusion
surgery. Dynamic spinal parameters correlated with static spinal parameters. The
successful group obtained significant improvement in maximal and minimal dynamic
LL than the unsuccessful group. CONCLUSION: The DFB group showed characteristic
lower limb and spinal angles in dynamic and static parameters. Correlation
between static and dynamic parameters was found in spinal segment. Dynamic LL was
good predictor of successful surgical outcomes.
PMID- 27606276
TI - Overall Profile of a Pediatric Multidisciplinary Feeding Clinic.
AB - OBJECTIVE: To evaluate the overall profile of children with feeding disorders and
their relationships to medical conditions in an outpatient feeding clinic of a
tertiary hospital. METHODS: The medical records of 143 children who had visited
the feeding clinic between January 2010 and June 2014 were reviewed
retrospectively. The presence of a feeding disorder (feeding behavior disorder,
dysphagia, and/or failure to thrive [FTT]) and the children's medical conditions
were examined by a physiatrist. RESULTS: Half of the patients (n=74, 51.7%) were
under 15 months of age, and 68 (47.6%) were born preterm. Ninety-three patients
(65.0%) met the criteria for any combination of feeding behavior disorder,
dysphagia, or FTT. Cardiorespiratory disease was the most common medical
condition; children with this condition were more likely to show sensory food
aversion and FTT. Feeding behavior disorders were significantly associated with
gastrointestinal problems, and dysphagia was significantly related to almost all
medical conditions. CONCLUSION: A multidisciplinary approach to children with
feeding difficulties is proposed for comprehensive evaluation and treatment
because combinations of feeding problems are very common among children. This
overall profile could provide clinicians with a clear understanding of the
complexity of feeding disorders and their relationships with various medical
conditions in children.
PMID- 27606277
TI - Shoulder Disease Patterns of the Wheelchair Athletes of Table-Tennis and Archery:
A Pilot Study.
AB - OBJECTIVE: To investigate the shoulder disease patterns for the table-tennis (TT)
and archery (AR) wheelchair athletes via ultrasonographic evaluations. METHODS: A
total of 35 wheelchair athletes were enrolled, made up of groups of TT (n=19) and
AR (n=16) athletes. They were all paraplegic patients and were investigated for
their wheelchair usage duration, careers as sports players, weekly training
times, the Wheelchair User's Shoulder Pain Index (WUSPI) scores and
ultrasonographic evaluation. Shoulders were divided into playing arm of TT, non
playing arm of TT, bow-arm of AR, and draw arm of AR athletes. Shoulder diseases
were classified into five entities of subscapularis tendinopathy, supraspinatus
tendinopathy, infraspinatus tendinopathy, biceps long head tendinopathy, and
subacromial-subdeltoid bursitis. The pattern of shoulder diseases were compared
between the two groups using the Mann-Whitney and the chi-square tests. RESULTS:
WSUPI did not significantly correlate with age, wheelchair usage duration, career
as players or weekly training times for all the wheelchair athletes. For the non
playing arm of TT athletes, there was a high percentage of subscapularis (45.5%)
and supraspinatus (40.9%) tendinopathy. The percentage of subacromial-subdeltoid
bursitis showed a tendency to be present in the playing arm of TT athletes
(20.0%) compared with their non-playing arm (4.5%), even though this was not
statistically significant. Biceps long head tendinopathy was the most common
disease of the shoulder in the draw arm of AR athletes, and the difference was
significant when compared to the non-playing arm of TT athletes (p<0.05).
CONCLUSION: There was a high percentage of subscapularis and supraspinatus
tendinopathy cases for the non-playing arm of TT wheelchair athletes, and a high
percentage of biceps long head tendinopathy for the draw arm for the AR
wheelchair athletes. Consideration of the biomechanical properties of each sport
may be needed to tailor specific training for wheelchair athletes.
PMID- 27606278
TI - Proposal and Evaluation of a Telerehabilitation Platform Designed for Patients
With Partial Rotator Cuff Tears: A Preliminary Study.
AB - OBJECTIVE: To propose and evaluate the effectiveness of a telerehabilitation
platform designed for patients with rotator cuff (RC) tears. METHODS: During the
first study phase, a virtual service platform that included information on RC
tear pathology, joint care, and a series of instructions regarding therapeutic
exercise was designed and created. Subsequently, in the clinical phase, a quasi
experimental study was performed. The platform was tested on patients and
evaluated at baseline and at 1, 2, 3, and 6 months with respect to their pain
levels and functionality on the Constant-Murley (CM) scale. RESULTS: Eleven
patients were included, 5 women and 6 men, with a median age of 55 years (range,
42-68 years). Pain diminished from a baseline value of 64 mm (range, 40-80 mm) to
16 mm (range, 0-30 mm) at 6 months (p<0.001). Points on the CM scale rose from a
baseline value of 54 points (range, 51-66 points) to 85 points (range, 70-100
points) at 6 months (p=0.001). Functionality in daily living and work activities,
movement, and strength exhibited significant changes at 6 months (p<0.05).
CONCLUSION: Significant changes were observed in pain and functionality in this
group of participants who used a telerehabilitation platform. To the best of our
knowledge, this is the first study that included a specific program for RC tears.
PMID- 27606279
TI - Factors Related to the Occurrence of Urinary Tract Infection Following a
Urodynamic Study in Patients With Spinal Cord Injury.
AB - OBJECTIVE: To analyze the factors related to urinary tract infection (UTI)
occurrence after an urodynamic study (UDS) in patients with spinal cord injury
(SCI). METHODS: We retrospectively investigated the medical records of 387
patients with SCI who underwent UDS with prophylactic antibiotic therapy between
January 2012 and December 2012. Among them, 140 patients met the inclusion
criteria and were divided into two groups, UTI and non-UTI. We statistically
analyzed the following factors between the two groups: age, sex, level of injury,
SCI duration, spinal cord independence measure, non-steroidal anti-inflammatory
drug use, diabetes mellitus, the American Spinal Injury Association impairment
scale (AIS), lower extremity spasticity, a history of UTI within the past 4 weeks
prior to the UDS, symptoms and signs of neurogenic bladder, urination methods,
symptoms during the UDS and UDS results. RESULTS: Among the 140 study
participants, the UTI group comprised 12 patients and the non-UTI group comprised
128 patients. On univariate analysis, a history of UTI within the past 4 weeks
prior to the UDS was significant and previous autonomic dysreflexia before the
UDS showed a greater tendency to influence the UTI group. Multivariable logistic
regression analysis using these two variables showed that the former variable was
significantly associated with UTI and the latter variable was not significantly
associated with UTI. CONCLUSION: In patients with SCI, a history of UTI within
the past 4 weeks prior to the UDS was a risk factor for UTI after the UDS
accompanied by prophylactic antibiotic therapy. Therefore, more careful pre
treatment should be considered when these patients undergo a UDS.
PMID- 27606280
TI - Energy Expenditures for Activities of Daily Living in Korean Young Adults: A
Preliminary Study.
AB - OBJECTIVE: To investigate the energy expenditure (EE) of Korean young adults
based on activities refined to a deskbound lifestyle. METHODS: Sixty-four healthy
office workers aged between 25 and 46 years participated in this study. EE was
expressed as metabolic equivalent of task (MET). Participants were evaluated in
terms of their EE during physical activities of sleeping (n=22), typing (n=37),
folding laundry (n=34), dishwashing (n=32), studying (n=18), mopping (n=35),
walking (n=33), stair climbing (n=23), and running (n=29). Volume of oxygen
consumption was measured by indirect calorimetry K4b(2) (COSMED). The results
were compared to the established Compendium MET. RESULTS: The MET of activities
were: sleeping, 1.24+/-0.43; typing, 1.35+/-0.25; folding laundry, 1.58+/-0.51;
dishwashing, 2.20+/-0.51; studying, 2.11+/-0.90; mopping, 2.72+/-0.69; walking at
4 km/hr, 3.48+/-0.65; stair climbing of five stories, 6.18+/-1.08; and running at
8 km/hr, 7.57+/-0.57. The values of typing and mopping were similar to those in
the Compendium, whereas those of sleeping, folding laundry, dishwashing,
studying, walking, stair climbing and running were different. CONCLUSION: To our
knowledge, this estimation of EE in MET during activities of daily living is the
first data of young adults in Korea. These data could be used as a reference to
modify the guidelines of physical activities for the age group examined in this
study.
PMID- 27606281
TI - Progressive Bilateral Facial Palsy as a Manifestation of Granulomatosis With
Polyangiitis: A Case Report.
AB - Bilateral facial palsy, which is usually combined with other diseases, occurs
infrequently. It may imply a life-threatening condition. Therefore, the
differential diagnosis of bilateral facial palsy is important. However, the
etiology is variable, which makes diagnosis challenging. We report a rare case of
progressive bilateral facial palsy as a manifestation of granulomatosis with
polyangiitis (GPA). A 40-year-old male with otitis media and right facial palsy
was referred for electroneurography (ENoG), which showed a 7.7% ENoG. Left facial
palsy occurred after 2 weeks, and multiple cavitary opacities were noted on chest
images. GPA was diagnosed by lung biopsy. His symptoms deteriorated and
mononeuropathy multiplex developed. The possibility of systemic disease, such as
GPA, should be considered in patients presenting with bilateral facial palsy, the
differential diagnosis of which is summarized in this report.
PMID- 27606282
TI - Pudendal Nerve Entrapment Syndrome due to a Ganglion Cyst: A Case Report.
AB - Pudendal nerve entrapment syndrome is an unusual cause of chronic pelvic pain. We
experienced a case of pudendal neuralgia associated with a ganglion cyst. A 60
year-old male patient with a tingling sensation and burning pain in the right
buttock and perineal area visited our outpatient rehabilitation center. Pelvis
magnetic resonance imaging showed the presence of multiple ganglion cysts around
the right ischial spine and sacrospinous ligament, and the pudendal nerve and
vessel bundle were located between the ischial spine and ganglion cyst at the
entrance of Alcock's canal. We aspirated the lesions under ultrasound guidance,
and consequently his symptoms subsided during a 6-month follow-up. This is the
first report of pudendal neuralgia caused by compression from a ganglion cyst
around the sacrospinous ligament.
PMID- 27606283
TI - A Comprehensive Rehabilitation Approach in a Patient With Serious
Neuropsychiatric Systemic Lupus Erythematosus.
AB - Neuropsychiatric systemic lupus erythematosus (NPSLE) involves the central and
peripheral nervous system in patients with systemic lupus erythematosus (SLE). It
is essential to specify the problems faced by patients with NPSLE because it
causes diverse disabilities and impairs quality of life. After performing a
comprehensive evaluation, tailored management should be provided for the
patient's specific problems. We report here the case of a 30-year-old female with
SLE who experienced serious neuropsychiatric symptoms cerebral infarction
followed by posterior reversible encephalopathy syndrome and peripheral
polyneuropathy. We systemically assessed the patient using the International
Classification of Functioning, Disability and Health model as a clinical problem
solving tool and provided comprehensive rehabilitation by focusing on her
problems.
PMID- 27606284
TI - Acute Pseudobulbar Palsy After Bilateral Paramedian Thalamic Infarction: A Case
Report.
AB - Bilateral paramedian thalamic infarction is a rare subtype of stroke caused by
occlusion of the artery of Percheron, an uncommon variant originating from one of
the posterior cerebral arteries. This type of stroke has several major clinical
presentations: altered mental status, behavioral amnestic impairment, aphasia or
dysarthria, ocular movement disorders, motor deficits, cerebellar signs, and
others. Few cases of bilateral paramedian thalamic infarction-related
pseudobulbar palsy characterized by dysarthria, dysphagia, and facial and tongue
weakness have been reported. We report here a rare case of acute severe
pseudobulbar palsy as a manifestation of bilateral paramedian thalamic
infarction.
PMID- 27606285
TI - MLH1 Ile219Val Polymorphism in Argentinean Families with Suspected Lynch
Syndrome.
PMID- 27606287
TI - Breast cancer: Indian experience, data, and evidence.
PMID- 27606286
TI - Tight Junction Disruption Induced by Type 3 Secretion System Effectors Injected
by Enteropathogenic and Enterohemorrhagic Escherichia coli.
AB - The intestinal epithelium consists of a single cell layer, which is a critical
selectively permeable barrier to both absorb nutrients and avoid the entry of
potentially harmful entities, including microorganisms. Epithelial cells are held
together by the apical junctional complexes, consisting of adherens junctions,
and tight junctions (TJs), and by underlying desmosomes. TJs lay in the apical
domain of epithelial cells and are mainly composed by transmembrane proteins such
as occludin, claudins, JAMs, and tricellulin, that are associated with the
cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3,
connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting
TJ to the microtubule network. Extracellular bacteria such as EPEC and EHEC
living in the intestinal lumen inject effectors proteins directly from the
bacterial cytoplasm to the host cell cytoplasm, where they play a relevant role
in the manipulation of the eukaryotic cell functions by modifying or blocking
cell signaling pathways. TJ integrity depends on various cell functions such as
actin cytoskeleton, microtubule network for vesicular trafficking, membrane
integrity, inflammation, and cell survival. EPEC and EHEC effectors target most
of these functions. Effectors encoded inside or outside of locus of enterocyte
effacement (LEE) disrupt the TJ strands. EPEC and EHEC exploit the TJ dynamics to
open this structure, for causing diarrhea. EPEC and EHEC secrete effectors that
mimic host proteins to manipulate the signaling pathways, including those related
to TJ dynamics. In this review, we focus on the known mechanisms exploited by
EPEC and EHEC effectors for causing TJ disruption.
PMID- 27606288
TI - Breast cancer: An overview of published Indian data.
AB - The Incidence of breast cancer has been steadily increasing in the last two
decades, more so in urban areas of the sub-continent. Cancer ceters across the
country have large numbers of patients being treated with multiple publications
in this field. Inspite of paucity of prospective data and randomised clinical
trials from India, there are large number of retrospective publications on
various aspects of the disease including pathology, radiology, surgery,
chemotherapy, radiation, palliative care and alternatitive treatment modalities.
These published data provide an insight into the trends of breast cancer in the
country and this comprehensive data review of Indian data will provide a basis
for designing trials relevant to our population and planning health care.
PMID- 27606289
TI - Lung cancer in India: Current status and promising strategies.
PMID- 27606290
TI - Lung cancer in the Indian subcontinent.
AB - Smoking tobacco, both cigarettes and beedis, is the principal risk factor for
causation of lung cancer in Indian men; however, among Indian women, the
association with smoking is not strong, suggesting that there could be other risk
factors besides smoking. Despite numerous advances in recent years in terms of
diagnostic methods, molecular changes, and therapeutic interventions, the
outcomes of the lung cancer patients remain poor; hence, a better understanding
of the risk factors may impact the preventive measures to be implemented at the
community level. There is a lack of comprehensive data on lung cancer in India.
In this review, we attempt to collate the available data on lung cancer from
India.
PMID- 27606291
TI - Head and neck oncology: The Indian scenario.
PMID- 27606293
TI - Editorial on the topic: Gynecological cancers: A summary of published Indian
data.
PMID- 27606292
TI - The Indian scenario of head and neck oncology - Challenging the dogmas.
AB - Head and neck cancers (HNCs) are the most common malignancies worldwide. Asian
populations bear major burden of this disease, with certain unique
characteristics. Although significant research in HNCs is ongoing globally, many
clinical issues still remain unanswered. We performed a literature search to find
noteworthy Indian studies that changed practice of HNC as well as to look for
areas for further research in this field. Many randomized controlled trials as
well as large patient series are reported in the field of radiotherapy,
chemotherapy, and surgical management of HNC. Still, many areas such as
palliative therapy, targeted agents, and newer chemotherapeutic agents remain
unexplored. Planned collaborative research is need of the hour to provide more
evidenced based.
PMID- 27606295
TI - Genitourinary malignancies in India: Laying the foundations for the future.
PMID- 27606294
TI - Gynecological cancers: A summary of published Indian data.
AB - Gynecological cancers are among the most common cancers in women and hence an
important public health issue. Due to the lack of cancer awareness, variable
pathology, and dearth of proper screening facilities in developing countries such
as India, most women report at advanced stages, adversely affecting the prognosis
and clinical outcomes. Ovarian cancer has emerged as one of the most common
malignancies affecting women in India and has shown an increase in the incidence
rates over the years. Although cervical cancer is on a declining trend, it
remains the second most common cancer in women after breast cancer. Many
researchers in India have published important data in the field of gynecologic
oncology, covering all domains such as basic sciences, preventive oncology,
pathology, radiological imaging, and clinical outcomes. This work has given us an
insight into the in-depth understanding of these cancers as well as the
demographics and survival rates in the Indian population. This aim of this review
is to discuss the important studies done in India for all gynecological cancers.
PMID- 27606296
TI - Genitourinary cancers: Summary of Indian data.
AB - Tumors of the genitourinary system are one of the most common tumors encountered
in clinical practice. The associated morbidity and mortality and the significant
proportion of affected middle-age individuals have a major bearing on the death
adjusted life years compared to other malignancies. Genitourinary system tumors
encompass a very broad spectrum with regard to age, location, histology, and
clinical outcomes. Advances in diagnostic imaging, surgical techniques,
radiotherapy equipment, and generation of newer chemotherapeutic and targeted
agents over the past few years have helped improving treatment outcome. Several
focused groups within India have been working on a range of topics related to
genitourinary system tumors, and a significant body of work from India in the
recent years is being increasingly recognized throughout the world. The present
article summarizes the key published work related to the epidemiology of
genitourinary system tumors in the Indian setting. A PubMed search was made for
locating and selecting articles relevant to the topic.
PMID- 27606297
TI - Gastrointestinal cancers in India: Treatment perspective.
PMID- 27606299
TI - Sarcomas: Difficult to tame tumors!
PMID- 27606298
TI - Gastrointestinal cancers in India: Treatment perspective.
AB - GI cancer is not one cancer but is a term for the group of cancers that affect
the digestive system including gastric cancer (GC), colorectal cancer (CRC),
hepatocellular carcinoma (HCC), esophageal cancer (EC), and pancreatic cancer
(PC). Overall, the GI cancers are responsible for more cancers and more deaths
from cancer than any other organ. 5 year survival of these cancers remains low
compared to western world. Unlike the rest of the world where organ based
specialities hepatobiliary, pancreatic, colorectal and esophagogastric exist,
these cancers are managed in India by either a gastrointestinal surgeons,
surgical oncologist, or a general surgeon with varying outcomes. The aim of this
review was to collate data on GI cancers in indian continent. In colorectal
cancers, data from tertiary care centres identifies the unique problem of
mucinous and signet colorectal cancer. Results of rectal cancer resection in
terms of technique (intersphincteric resection, extralevator aper, minimal
invasive approach) to be comparable with world literature. However long term
outcome and data regarding colon cancers and nationally is needed. Gastric cancer
at presentation are advanced and in surgically resected patients, there is need
for a trial to compare chemoradiation vs chemotherapy alone to prevent loco
regional recurrence. Data on minimal invasive gastric cancer surgery may be
sparse for the same reason. Theree is a lot of data on surgical techniques and
perioperatve outcomes in pancreatic cancer. There is a high volume of locally
advanced gallbladder cancers with efforts on to decide whether neoadjuvant
chemotherapy or neoadjuvant chemoradiotherapy is better for down staging.
Considering GI cancers, a heterogeneous disease with site specific treatment
options and variable outcomes, the overall data and outcomes are extremely
variable. Young patients with pathology unique to the Indian subcontinent (for
example, signet ring rectal cancer, GBCs) need focussed attention. Solution for
such pathology needs to come from the Indian continent itself. Joint efforts to
improve outcomes for GI cancer can be integrated under the national cancer grid
program.
PMID- 27606301
TI - Central nervous system tumors: Spotlight on India.
PMID- 27606300
TI - Indian data on bone and soft tissue sarcomas: A summary of published study
results.
AB - Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with
osteosarcoma (OGS), chondrosarcoma, and Ewing sarcoma being the most common
cancers in this subset. The formation of disease management groups/clinics
focused on sarcomas has resulted in better understanding and management of these
uncommon tumors. Multiple large-scale retrospective data from Tata Memorial
Hospital (TMH) and All India Institute of Medical Sciences have reported outcomes
comparable to Western data in the field of OGS and Ewing sarcoma, with
interesting prognostic factors identified for further evaluation. Soft tissue
sarcomas are a rare heterogeneous group of tumors, more than 50 different tumor
entities. The common subtypes identified in India include Ewing sarcoma and
synovial sarcoma. Valuable work regarding brachytherapy has been done by
radiation oncologists from the TMH, especially in pediatric patients.
PMID- 27606303
TI - Acute childhood leukemia in India: Where are we going, where have we been?
PMID- 27606302
TI - Indian data on central nervous tumors: A summary of published work.
AB - Tumors of the central nervous system (CNS) constitute approximately 2% of all
malignancies. Although relatively rare, the associated morbidity and mortality
and the significant proportion of affected young and middle-aged individuals has
a major bearing on the death-adjusted life years compared to other malignancies.
CNS tumors encompass a very broad spectrum with regards to age, location,
histology, and clinical outcomes. Advances in diagnostic imaging, surgical
techniques, radiotherapy equipment, and generation of newer chemotherapeutic and
targeted agents over the past few years have helped improving treatment outcome.
Further insights into the molecular pathways leading to the development of tumors
made in the past decade are being incorporated into routine clinical practice.
Several focused groups within India have been working on a range of topics
related to CNS tumors, and a significant body of work from India, in the recent
years, is being increasingly recognized throughout the world. The present article
summarizes key published work with particular emphasis on gliomas and
medulloblastoma, the two commonly encountered tumors.
PMID- 27606305
TI - Chronic myeloid leukemia: An Indian scenario.
PMID- 27606304
TI - Acute leukemia in children: A review of the current Indian data.
AB - Acute leukemias are the most common diagnostic group of childhood cancer. This
review summarizes the published literature on reported current outcomes of
childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)
from India. Overall survival in ALL ranged from 45% to 81% (commonly >60%) and
event-free survival ranged from 41% to 70% (commonly >50%). Outcome data for AML
was patchy with varying duration of follow-up, but it can be inferred that 50-80%
of treated patients had experienced an event (toxic death, refractory disease or
relapse). It is imperative that going forward focus should be on collaborative
efforts, which promote treatment of patients on risk-stratified adapted protocols
based on local infrastructure, improvement in supportive care and encourage
prospective multi-center clinical trials.
PMID- 27606307
TI - Erratum: The relationship between histologic grades of invasive carcinoma of
breast ducts and mast cell infiltration.
AB - [This corrects the article on p. 5 in vol. 5, PMID: 27169108.].
PMID- 27606306
TI - Summary of the published Indian data on chronic myeloid leukemia.
AB - Chronic myelogenous leukemia (LML) was recognized as a distinct entity in the mid
1800s. Since Nowell and Hunagerford initiated their research on CML in1960 our
understanding in CML has been increasing. Imatinib became the preferred treatment
from 2000 onwards as a result of its unprecedented success. The lack of
structured Indian data on CML led to the formation of a CML data cansortuim which
invited CML data albiet retro spartive form around the country including major
cancer service providers both government and private. We provide a summary of
published Indian data on CML here.
PMID- 27606308
TI - Model of Care for Adolescents and Young Adults with Cancer: The Youth Project in
Milan.
AB - Adolescents and young adults (AYA) with cancer form a particular group of
patients with unique characteristics, who inhabit a so-called "no man's land"
between pediatric and adult services. In the last 10 years, the scientific
oncology community has started to pay attention to these patients, implementing
dedicated programs. A standardized model of care directed toward patients in this
age range has yet to be developed and neither the pediatric nor the adult
oncologic systems perfectly fit these patients' needs. The Youth Project of the
Istituto Nazionale Tumori in Milan, dedicated to AYA with pediatric-type solid
tumors, can be seen as a model of care for AYA patients, with its heterogeneous
multidisciplinary staff and close cooperation with adult medical oncologists and
surgeons. Further progress in the care of AYA cancer patients is still needed to
improve their outcomes.
PMID- 27606310
TI - NGOs, Foreign Aid, and Development in Nepal.
AB - The number of non-governmental organizations (NGOs) working in Nepal has grown
significantly since the 1990s due to a range of factors. A total of 39,759 NGOs
and 189 international non-governmental organizations were registered in Nepal
between 1977 and 2014 in various sectors, including health, agriculture, poverty
alleviation, and good governance. Despite thousands of NGOs and significant
amounts of foreign aid, Nepal remains one of the poorest countries in South Asia.
The case of Nepal indicates that aid and donor support alone are insufficient for
sustained development.
PMID- 27606309
TI - Sedation in Critically Ill Children with Respiratory Failure.
AB - This article discusses the rationale of sedation in respiratory failure, sedation
goals, how to assess the need for sedation as well as effectiveness of
interventions in critically ill children, with validated observational sedation
scales. The drugs and non-pharmacological approaches used for optimal sedation in
ventilated children are reviewed, and specifically the rationale for drug
selection, including short- and long-term efficacy and safety aspects of the
selected drugs. The specific pharmacokinetic and pharmacodynamic aspects of
sedative drugs in the critically ill child and consequences for dosing are
presented. Furthermore, we discuss different sedation strategies and their
adverse events, such as iatrogenic withdrawal syndrome and delirium. These
principles can guide clinicians in the choice of sedative drugs in pediatric
respiratory failure.
PMID- 27606312
TI - Clinical Utility of Combinatorial Pharmacogenomics-Guided Antidepressant Therapy:
Evidence from Three Clinical Studies.
AB - DNA of 258 patients with treatment-resistant depression was collected in three 8
10 week, two-arm, prospective clinical trials. Forty-four allelic variations were
measured in genes for the cytochrome P450 (CYP) enzymes CYP2D6, CYPC19, and
CYP1A2, the serotonin transporter (SLC6A4), and the 5-HT2A receptor (HTR2A). The
combinatorial pharmacogenomic (CPGxTM) GeneSight test results were provided to
clinicians to support medication changes from baseline (guided arm), or they were
provided at the end of each study to clinicians of unguided patients who were
treated as usual (TAU). TAU subjects who at baseline were prescribed medications
genetically discordant for them showed only a 12% symptom improvement, far less
than the 32.5% or 28.5% improvements of the TAU subjects on yellow-category ('use
with caution'; p = 0.002) or green-category medications ('use as recommended'; p
= 0.02), respectively. The odds of a clinical response were increased 2.3-fold
among all GeneSight-guided compared to all TAU subjects (p = 0.004), and overall,
the guided group had a 53% greater improvement in depressive symptoms (p =
0.0002), a 1.7-fold relative improvement in response (p = 0.01), and a number
needed to treat for one clinical response above that seen in the TAU group of
6.07.
PMID- 27606311
TI - Adenosine A2B Receptor: From Cell Biology to Human Diseases.
AB - Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide
array of biological processes. Recently, significant advances have been made in
our understanding of A2B adenosine receptor (A2BAR). In this review, we first
summarize some of the general characteristics of A2BAR, and then we describe the
multiple binding partners of the receptor, such as newly identified alpha-actinin
1 and p105, and discuss how these associated proteins could modulate A2BAR's
functions, including certain seemingly paradoxical functions of the receptor.
Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and
diabetes, in addition to its importance in the regulation of vascular diseases,
and lung disease. Here, we also discuss the role of A2BAR in cancer, renal
disease, and diabetes and the potential of the receptor as a target for treating
these three diseases.
PMID- 27606313
TI - Neural Correlates of Schizophrenia Negative Symptoms: Distinct Subtypes Impact
Dissociable Brain Circuits.
AB - BACKGROUND: The negative symptoms of schizophrenia include deficits in emotional
expression and motivation. These deficits are stable over the course of illness
and respond poorly to current medications. Previous studies have focused on
negative symptoms as a single category; however, individual symptoms might be
related to separate neurological disturbances. We analyzed data from the
Functional Biomedical Informatics Research Network dataset to explore the
relationship between individual negative symptoms and functional brain activity
during an auditory oddball task. METHODS: Functional magnetic resonance imaging
was conducted on 89 schizophrenia patients and 106 healthy controls during a two
tone auditory oddball task. Blood oxygenation level-dependent (BOLD) signal
during the target tone was correlated with severity of five negative symptom
domains from the Scale for the Assessment of Negative Symptoms. RESULTS: The
severity of alogia, avolition/apathy and anhedonia/asociality was negatively
correlated with BOLD activity in distinct sets of brain regions associated with
processing of the target tone, including basal ganglia, thalamus, insular cortex,
prefrontal cortex, posterior cingulate and parietal cortex. CONCLUSIONS:
Individual symptoms were related to different patterns of functional activation
during the oddball task, suggesting that individual symptoms might arise from
distinct neural mechanisms. This work has potential to inform interventions that
target these symptom-related neural disruptions.
PMID- 27606314
TI - SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and
Anterior Cingulate Cortex.
AB - SNAP-25 is a neurotransmitter vesicular docking protein which has been associated
with brain disorders such as attention deficit hyperactivity disorder, bipolar
disorder and schizophrenia. In this project, we were interested if clinical
factors are associated with differential SNAP-25 expression. We examined the SNAP
25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9)
and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical
variables including mood state in the last week of life and lifetime
impulsiveness. We found affected subjects with a diagnosis of alcohol use
disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those
without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than
Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25
BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic
symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the
high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than
normal controls. These data expand our understanding of clinical factors
associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may
be useful biomarkers beyond limited neurological and psychiatric diagnostic
categories.
PMID- 27606315
TI - Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in
22q11.2 Deletion Syndrome.
AB - 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with
elevated rates of developmental neuropsychiatric disorders and impaired executive
function (EF). Disrupted brain structure-function relationships may underlie EF
deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive
Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched
controls (n = 86; age 6-17 years), along with cognitive measures that tap
behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole
brain vertex cortical thickness pipeline, we investigated brain structure-EF
relationships in patients with 22q11DS and controls. Behaviorally, patients with
22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical
thickness showed a differential relationship between real-world EF in patients
with 22q11DS and controls. We also observed a group difference in the
relationship between behavioral regulation and metacognition measures with
thickness of ventral and dorsolateral prefrontal regions, respectively. Our
findings suggest that executive dysfunction characteristic of 22q11DS is
underscored by altered prefrontal cortical structure.
PMID- 27606317
TI - A Case for Returning to Multiplex Families for Further Understanding the
Heritability of Schizophrenia: A Psychiatrist's Perspective.
AB - The genetic mechanism for schizophrenia still remains unknown despite decades of
research. A tremendous amount of investigator time and effort has gone into
ascertainment of clinical samples for genetic studies over the years. Most
recently, a large international effort of unprecedented collaboration has
occurred to combine data worldwide in pursuit of uncovering the relevant genetic
risk factors. However, in the process, the use of multiplex families to
understand the genetics has waned, and it has been presumed that large resources
of unrelated patients and controls are more efficient to find risk alleles than
families. This commentary is a call to return to the use of this largely
abandoned resource for further understanding the underlying biological mechanism
of this serious mental illness.
PMID- 27606318
TI - Cell Type-Specific Effects of Mutant DISC1: A Proteomics Study.
AB - Despite the recent progress in psychiatric genetics, very few studies have
focused on genetic risk factors in glial cells that, compared to neurons, can
manifest different molecular pathologies underlying psychiatric disorders. In
order to address this issue, we studied the effects of mutant disrupted in
schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured
primary neurons and astrocytes using an unbiased mass spectrometry-based
proteomic approach. We found that selective expression of mutant DISC1 in neurons
affects a wide variety of proteins predominantly involved in neuronal development
(e.g., SOX1) and vesicular transport (Rab proteins), whereas selective expression
of mutant DISC1 in astrocytes produces changes in the levels of mitochondrial
(GDPM), nuclear (TMM43) and cell adhesion (ECM2) proteins. The present study
demonstrates that DISC1 variants can perturb distinct molecular pathways in a
cell type-specific fashion to contribute to psychiatric disorders through
heterogenic effects in diverse brain cells.
PMID- 27606316
TI - Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical
Implications.
AB - Antipsychotic medications (APs), particularly second-generation APs, are
associated with significant weight gain in schizophrenia patients. Recent
evidence suggests that the immune system may contribute to antipsychotic-induced
weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics
with a high propensity for weight gain, such as clozapine and olanzapine,
influence the expression of immune genes, and induce changes in serum cytokine
levels to ultimately down-regulate neuroinflammation. Since inflammatory
cytokines are normally involved in anorexigenic responses, reduced inflammation
has been independently shown to mediate changes in feeding behaviours and other
metabolic parameters, resulting in obesity. Genetic variation in pro-inflammatory
cytokines is also associated with both general obesity and weight change during
AP treatment, and thus, may be implicated in the pharmacogenetics of AIWG. At
this time, preliminary data support a cytokine-mediated model of AIWG which may
have clinical utility in developing more effective metabolic monitoring
guidelines and prevention measures. However, further research is still needed to
clearly elucidate the validity of this immune model. This article reviews the
evidence implicating inflammatory cytokines in AIWG and its potential clinical
relevance.
PMID- 27606319
TI - A Review of Genome-Wide Association Studies of Stimulant and Opioid Use
Disorders.
AB - Substance use disorders (SUD) are a major contributor to disability and disease
burden worldwide. Risk for developing SUDs is influenced by variation in the
genome. Identifying the genetic variants that influence SUD risk may help us to
understand the biological mechanisms for the disorders and improve treatments.
Genome-wide association studies (GWAS) have been successful in identifying many
regions of the genome associated with common human disorders. Here, findings from
recent GWAS of SUDs that involve illicit substances will be reviewed. Several
GWAS have been reported, including studies on opioid and stimulant use disorder
(cocaine and methamphetamine). Several of these GWAS report associations that are
biologically interesting and statistically robust. Replication of the
associations in independent samples and functional studies to understand the
basis for the statistical associations will be important next steps.
PMID- 27606320
TI - Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a
Posttraumatic Stress Disorder Mouse Model.
AB - Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several
studies have attempted to characterize molecular alterations associated with
PTSD, but most findings were limited to the investigation of specific cellular
markers in the periphery or defined brain regions. In the current study, we aimed
to unravel affected molecular pathways/mechanisms in the fear circuitry
associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by
integrating proteomics and metabolomics profiling data. Alterations at the
proteome level were analyzed using in vivo (15)N metabolic labeling combined with
mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC),
basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus
between shocked and nonshocked (control) mice, with and without fluoxetine
treatment. In silico pathway analyses revealed an upregulation of the citric acid
cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc).
Chronic fluoxetine treatment prevented decreased citric acid cycle activity in
NAc and ACC and ameliorated conditioned fear response in shocked mice. Our
results shed light on the role of energy metabolism in PTSD pathogenesis and
suggest potential therapy through mitochondrial targeting.
PMID- 27606322
TI - Neuregulin 3 Knockout Mice Exhibit Behaviors Consistent with Psychotic Disorders.
AB - Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia
demonstrate that risk variants in NRG3 are associated with cognitive and
psychotic symptom severity, and several intronic single nucleotide polymorphisms
in NRG3 are associated with delusions in patients with schizophrenia. In order to
gain insights into the biological function of the gene, we generated a novel Nrg3
knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to
psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired
prepulse inhibition of the acoustic startle response, and deficient fear
conditioning. No gross cytoarchitectonic or layer abnormalities were noted in the
brain of KO mice. Our findings suggest that deletion of the Nrg3 gene leads to
alterations consistent with aspects of schizophrenia. We propose that KO mice
will provide a valuable animal model to determine the role of the NRG3 in the
molecular pathogenesis of schizophrenia and other psychotic disorders.
PMID- 27606324
TI - The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine
and Glutamatergic Synapse Formation in the Mammalian Forebrain.
AB - The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity
(PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine
formation and glutamatergic synapse formation in mammalian central nervous system
neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler
dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic
synapse inputs on their dendrites than control neurons. Neurons from mice
heterozygous for a semidominant Vangl2 mutation have similar but not identical
phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue
from adult mutant mice. Given increasing evidence linking psychiatric
pathophysiology to these subneuronal sites and structures, our findings
underscore the relevance of core PCP proteins including Vangl2 to the underlying
biology of major mental illnesses and their treatment.
PMID- 27606323
TI - Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates alpha
Aminoadipate as a Potential Biomarker for Bipolar Disorder.
AB - Many studies suggest the presence of aberrations in cellular metabolism in
bipolar disorder. We studied the metabolome in bipolar disorder to gain insight
into cellular pathways that may be dysregulated in bipolar disorder and to
discover evidence of novel biomarkers. We measured polar and nonpolar metabolites
in fibroblasts from subjects with bipolar I disorder and matched healthy control
subjects, under normal conditions and with two physiologic perturbations: low
glucose media and exposure to the stress-mediating hormone dexamethasone.
Metabolites that were significantly different between bipolar and control
subjects showed distinct separation by principal components analysis methods. The
most statistically significant findings were observed in the perturbation
experiments. The metabolite with the lowest p value in both the low-glucose and
dexamethasone experiments was alpha-aminoadipate, whose intracellular level was
consistently lower in bipolar subjects. Our study implicates alpha-aminoadipate
as a possible biomarker in bipolar disorder that manifests under cellular stress.
This is an intriguing finding given the known role of alpha-aminoadipate in the
modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid
levels have been implicated in bipolar disorder.
PMID- 27606321
TI - Genetics of Common Antipsychotic-Induced Adverse Effects.
AB - The effectiveness of antipsychotic drugs is limited due to accompanying adverse
effects which can pose considerable health risks and lead to patient
noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic
biomarkers that can predict individual susceptibility to antipsychotic-induced
adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the
literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on
findings that have been independently replicated and which have additionally been
listed to be of interest by PGx expert panels. Gene-drug associations meeting
these criteria primarily pertain to metabolic dysregulation, extrapyramidal
symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation,
results have reaffirmed HTR2C as a strong candidate with potential clinical
utility, while MC4R and OGFR1 gene loci have emerged as new and promising
biomarkers for the prediction of weight gain. As for EPS and TD, additional
evidence has accumulated in support of an association with CYP2D6 metabolizer
status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with
the potential to predict differential susceptibility to TD. Overall, considerable
progress has been made within the field of psychiatric PGx, with inroads toward
the development of clinical tools that can mitigate AAEs. Going forward, studies
placing a greater emphasis on multilocus effects will need to be conducted.
PMID- 27606325
TI - Erdheim-Chester Disease: A Rare Presentation of a Rare Disease.
AB - Erdheim-Chester disease (ECD) is a rare, xanthogranulomatous, non-Langerhans cell
histiocytosis with frequent systemic involvement. Although the diagnosis is based
on characteristic histological and radiological findings, its identification can
be challenging because of its heterogeneous presentation. Osteosclerosis of long
bones, often associated with bone pain, is the most common initial manifestation,
followed by extraskeletal manifestations in approximately 50% of cases. There is
no standard treatment for ECD, although recommendations have been made on the
basis of small studies. A systematic approach to the diagnosis of ECD is
important, because its manifestations may be life-threatening and may require
specific management. We report an atypical presentation of ECD, with early
cardiac, renal, and central nervous system involvement, and only late skeletal
manifestations.
PMID- 27606326
TI - Accuracy of Suture Passage During Arthroscopic Remplissage-What Anatomic
Landmarks Can Improve It?: A Cadaveric Study.
AB - BACKGROUND: Recent data suggest that inaccurate suture passage during remplissage
may contribute to a loss of external rotation, with the potential to cause
posterior shoulder pain because of the proximity to the musculotendinous
junction. PURPOSE: To evaluate the accuracy of suture passage during remplissage
and identify surface landmarks to improve accuracy. STUDY DESIGN: Descriptive
laboratory study. METHODS: Arthroscopic remplissage was performed on 6 cadaveric
shoulder specimens. Two single-loaded suture anchors were used for each
remplissage. After suture passage, position was recorded in reference to the
posterolateral acromion (PLA), with entry perpendicular to the humeral surface.
After these measurements, the location of posterior cuff penetration was
identified by careful surgical dissection. RESULTS: Twenty-four sutures were
passed in 6 specimens: 6 sutures (25.0%) were correctly passed through the
infraspinatus tendon, 12 (50%) were through the infraspinatus muscle or
musculotendinous junction (MTJ), and 6 (25%) were through the teres minor. Suture
passage through the infraspinatus were on average 25 +/- 5.4 mm inferior to the
PLA, while sutures passing through the teres minor were on average 35.8 +/- 5.7
mm inferior to the PLA. There was an odds ratio of 25 (95% CI, 2.1-298.3; P <
.001) that the suture would be through the infraspinatus if the passes were less
than 3 cm inferior to the PLA. Sutures passing through muscle and the MTJ were
significantly more medial than those passing through tendon, measuring on average
8.1 +/- 5.1 mm lateral to the PLA compared with 14.5 +/- 5.5 mm (P < .02). If
suture passes were greater than 1 cm lateral to the PLA, it was significantly
more likely to be in tendon (P = .013). CONCLUSION: We found remplissage suture
passage was inaccurate, with only 25% of sutures penetrating the infraspinatus
tendon. Passing sutures 1 cm lateral and within 3 cm inferior of the PLA improves
the odds of successful infraspinatus tenodesis. We recommend this "safe zone" to
improve the odds of infraspinatus tenodesis during remplissage. These results may
help improve remplissage techniques and prevent previously reported
complications, including external rotation loss and pain from myodesis.
PMID- 27606327
TI - Dissecting the role of Wnt signaling and its interactions with FGF signaling
during midbrain neurogenesis.
AB - Interactions between FGF and Wnt/ bcat signaling control development of the
midbrain. The nature of this interaction and how these regulate patterning,
growth and differentiation is less clear, as it has not been possible to
temporally dissect the effects of one pathway relative to the other. We have
employed pharmacological and genetic tools to probe the temporal and spatial
roles of FGF and Wnt in controlling the specification of early midbrain neurons.
We identify a beta-catenin (bcat) independent role for GSK-3 in modulating FGF
activity and hence neuronal patterning. This function is complicated by an
overlap with bcat-dependent regulation of FGF signaling, through the regulation
of sprouty4. Additionally we reveal how attenuation of Axin protein function can
promote fluctuating levels of bcat activity that are dependent on FGF activity.
This highlights the complex nature of the interactions between FGF and Wnt/ bcat
and reveals that they act at multiple levels to control each others activity in
the midbrain.
PMID- 27606328
TI - Rheb1 mediates DISC1-dependent regulation of new neuron development in the adult
hippocampus.
AB - A large number of susceptibility genes have been implicated in psychiatric
disorders with a developmental origin, yet their biological roles and signaling
mechanisms in neurodevelopment are largely unknown. Disrupted-In-Schizophrenia 1
(DISC1), a susceptibility gene for several major psychiatric disorders, regulates
the development of newborn neurons in the adult hippocampus. Systemic
pharmacological inhibition of mTOR signaling with rapamycin has been shown to
rescue DISC1 deficiency-induced neurodevelopmental defects, as well as cognitive
and affective deficits. Whether mTOR signaling plays a cell-autonomous and/or non
cell-autonomous role in DISC1-dependent regulation of neuronal development is not
clear. Here we provide genetic evidence that hyper-activation of mTOR activator
Rheb1 (Ras homolog enriched in brain 1) in newborn neurons recapitulates DISC1
deficiency-induced neurodevelopmental defects, including neuronal morphogenesis
and migration. We further show that genetic deletion of Rheb1 rescues those
defects in a cell-autonomous fashion in developing newborn neurons in the adult
hippocampus. Our genetic and functional studies demonstrate that Rheb1 acts as a
key mediator of DISC1-dependent regulation of mTOR signaling and neuronal
development during adult hippocampal neurogenesis.
PMID- 27606330
TI - How to make striatal projection neurons.
AB - Medium spiny neurons (MSNs) are the main projection neurons of the striatum and
are preferentially lost in Huntington's disease (HD). With no current cure for
this neurodegenerative disorder, the specificity of neuronal loss in the striatum
makes cell transplantation therapy an attractive avenue for its treatment. Also,
given that MSNs are particularly vulnerable in HD, it is necessary to understand
why these neurons degenerate in order to develop new therapeutic options. Both
approaches require access to human MSN progenitors and their mature neuronal
derivatives. Human embryonic stem cells and HD patient induced pluripotent stem
cells (together referred to as hPSCs) may serve as an unlimited source of such
tissue if they can be directed toward authentic striatal neuronal lineage.
Understanding the MSN differentiation pathway in the brain is therefore of
paramount importance for the generation of accurate protocols to obtain striatal
cells in vitro. The focus of this mini review will be on striatal development and
current methods to generate MSNs from hPSCs.
PMID- 27606329
TI - Neuronal specification exploits the inherent flexibility of cell-cycle gap
phases.
AB - Starting from pluripotent stem cells that virtually proliferate indefinitely, the
orderly emergence during organogenesis of lineage-restricted cell types
exhibiting a decreased proliferative capacity concurrently with an increasing
range of differentiation traits implies the occurrence of a stringent
spatiotemporal coupling between cell-cycle progression and cell differentiation.
A recent computational modeling study has explored in the context of neurogenesis
whether and how the peculiar pattern of connections among the proneural Neurog2
factor, the Hes1 Notch effector and antagonistically-acting G1-phase regulators
would be instrumental in this event. This study highlighted that the strong
opposition to G1/S transit imposed by accumulating Neurog2 and CKI enables a
sensitive control of G1-phase lengthening and terminal differentiation to occur
concomitantly with late-G1 exit. Contrastingly, Hes1 promotes early-G1 cell-cycle
arrest and its cell-autonomous oscillations combined with a lateral inhibition
mechanism help maintain a labile proliferation state in dynamic balance with
diverse cell-fate outputs, thereby, offering cells the choice to either keep self
renewing or differentiate into distinct cell types. These results, discussed in
connection with Ascl1-dependent neural differentiation, suggest that
developmental fate decisions exploit the inherent flexibility of cell-cycle gap
phases to generate diversity by selecting subtly-differing patterns of
connections among components of the cell-cycle machinery and differentiation
pathways.
PMID- 27606331
TI - Neuronal cell-type-specific alternative splicing: A mechanism for specifying
connections in the brain?
AB - Alternative splicing (AS) allows a single gene to generate multiple protein
isoforms. It has been hypothesized that AS plays a role in brain wiring by
increasing the number of cell recognition molecules necessary for forming
connections between neurons. Many studies have characterized isoform expression
patterns of various genes in the brain, but very few have addressed whether
specific isoforms play a functional role in neuronal wiring. In our recent work,
we reported the cell-type-specific AS of the cell recognition molecule Dscam2.
Exclusive expression of Dscam2 isoforms allows tightly associated neurons to
signal repulsion selectively within the same cell-types, without interfering with
one another. We show that preventing cell-specific isoform expression in 2
closely associated neurons disrupts their axon terminal morphology. We propose
that the requirement for isoform specificity extends to synapses and discuss
experiments that can test this directly. Factors that regulate Dscam2 cell-type
specific AS likely regulate the splicing of many genes involved in
neurodevelopment. These regulators of alternative splicing may act broadly to
control many genes involved in the development of specific neuron types.
Identifying these factors is a key step in understanding how AS contributes to
the brain connectome.
PMID- 27606332
TI - Engineered AAV vectors for improved central nervous system gene delivery.
AB - Adeno-associated viruses (AAV) are non-pathogenic members of the Parvoviridae
family that are being harnessed as delivery vehicles for both basic research and
increasingly successful clinical gene therapy. To address a number of delivery
shortcomings with natural AAV variants, we have developed and implemented
directed evolution-a high-throughput molecular engineering approach to generate
novel biomolecules with enhanced function-to create novel AAV vectors that are
designed to preferentially transduce specific cell types in the central nervous
system (CNS), including astrocytes, neural stem cells, and cells within the
retina. These novel AAV vectors-which have enhanced infectivity in vitro and
enhanced infectivity and selectivity in vivo-can enable more efficient studies to
further our understanding of neurogenesis, development, aging, and disease.
Furthermore, such engineered vectors may aid gene or cell replacement therapies
to treat neurodegenerative disease or injury.
PMID- 27606333
TI - Mechanisms of temporal identity regulation in mouse retinal progenitor cells.
AB - While much progress has been made in recent years toward elucidating the
transcription factor codes controlling how neural progenitor cells generate the
various glial and neuronal cell types in a particular spatial domain, much less
is known about how these progenitors alter their output over time. In the past
years, work in the developing mouse retina has provided evidence that a
transcriptional cascade similar to the one used in Drosophila neuroblasts might
control progenitor temporal identity in vertebrates. The zinc finger
transcription factor Ikzf1 (Ikaros), an ortholog of Drosophila hunchback, was
reported to confer early temporal identity in retinal progenitors and, more
recently, the ortholog of Drosophila castor, Casz1, was found to function as a
mid/late temporal identity factor that is negatively regulated by Ikzf1. The
molecular mechanisms by which these temporal identity factors function in retinal
progenitors, however, remain unknown. Here we briefly review previous work on the
vertebrate temporal identity factors in the retina, and propose a model by which
they might operate.
PMID- 27606334
TI - Cannabinoid receptor signaling induces proliferation but not neurogenesis in the
mouse olfactory epithelium.
AB - The olfactory epithelium actively generates neurons through adulthood, and this
neurogenesis is tightly regulated by multiple factors that are not fully defined.
Here, we examined the role of cannabinoids in the regulation of neurogenesis in
the mouse olfactory epithelium. In vivo proliferation and cell lineage studies
were performed in mice (C57BL/6 and cannabinoid type 1 and 2 receptor deficient
strains) treated with cannabinoids directly (WIN 55,212-2 or 2
arachidonylglycerol ether) or indirectly via inhibition of cannabinoid hydrolytic
enzymes. Cannabinoids increased proliferation in neonatal and adult mice, and had
no effect on proliferation in cannabinoid type 1 and 2 receptor deficient adult
mice. Pretreatment with the cannabinoid type1 receptor antagonist AM251 decreased
cannabinoid-induced proliferation in adult mice. Despite a cannabinoid-induced
increase in proliferation, there was no change in newly generated neurons or non
neuronal cells 16 d post-treatment. However, cannabinoid administration increased
apoptotic cell death at 72 hours post-treatment and by 16 d the level of
apoptosis dropped to control levels. Thus, cannabinoids induce proliferation, but
do not induce neurogenesis nor non-neuronal cell generation. Cannabinoid receptor
signaling may regulate the balance of progenitor cell survival and proliferation
in adult mouse olfactory epithelium.
PMID- 27606335
TI - Can manipulation of differentiation conditions eliminate proliferative cells from
a population of ES cell-derived forebrain cells?
AB - There is preliminary evidence that implantation of primary fetal striatal cells
provides functional benefit in patients with Huntington's disease, a
neurodegenerative condition resulting in loss of medium-sized spiny neurons (MSN)
of the striatum. Scarcity of primary fetal tissue means it is important to
identify a renewable source of cells from which to derive donor MSNs. Embryonic
stem (ES) cells, which predominantly default to telencephalic-like precursors in
chemically defined medium (CDM), offer a potentially inexhaustible supply of
cells capable of generating the desired neurons. Using an ES cell line, with the
forebrain marker FoxG1 tagged to the LacZ reporter, we assessed effects of known
developmental factors on the yield of forebrain-like precursor cells in CDM
suspension culture. Addition of FGF2, but not DKK1, increased the proportion of
FoxG1-expressing cells at day 8 of neural induction. Oct4 was expressed at day 8,
but was undetectable by day 16. Differentiation of day 16 precursors generated
GABA-expressing neurons, with few DARPP32 positive MSNs. Transplantation of day 8
precursor cells into quinolinic acid-lesioned striata resulted in generation of
teratomas. However, transplantation of day 16 precursors yielded grafts
expressing neuronal markers including NeuN, calbindin and parvalbumin, but no
DARPP32 6 weeks post-transplantation. Manipulation of fate of ES cells requires
optimization of both concentration and timing of addition of factors to culture
systems to generate the desired phenotypes. Furthermore, we highlight the value
of increasing the precursor phase of ES cell suspension culture when directing
differentiation toward forebrain fate, so as to dramatically reduce the risk of
teratoma formation.
PMID- 27606336
TI - Adult neural stem cell behavior underlying constitutive and restorative
neurogenesis in zebrafish.
AB - Adult Neural Stem Cells (aNSCs) generate new neurons that integrate into the pre
existing networks in specific locations of the Vertebrate brain. Moreover, aNSCs
contribute with new neurons to brain regeneration in some non-mammalian
Vertebrates. The similarities and the differences in the cellular and molecular
processes governing neurogenesis in the intact and regenerating brain are still
to be assessed. Toward this end, we recently established a protocol for non
invasive imaging of aNSC behavior in their niche in vivo in the adult intact and
regenerating zebrafish telencephalon. We observed different modes of aNSC
division in the intact brain and a novel mode of neurogenesis by direct
conversion, which contributes to stem cell depletion with age. After injury, the
generation of neurons is increased both by the activation of additional aNSCs and
a shift in the division mode of aNSCs, thereby contributing to the successful
neuronal regeneration. The cellular behavior we observed opens new questions
regarding long-term aNSC maintenance in homeostasis and in regeneration. In this
commentary we discuss our data and new questions arising in the context of aNSC
behavior, not only in zebrafish but also in other species, including mammals.
PMID- 27606337
TI - Mcidas and GemC1/Lynkeas specify embryonic radial glial cells.
AB - Ependymal cells are multiciliated cells located in the wall of the lateral
ventricles of the adult mammalian brain and are key components of the
subependymal zone niche, where adult neural stem cells reside. Through the
movement of their motile cilia, ependymal cells control the cerebrospinal fluid
flow within the ventricular system from which they receive secreted molecules and
morphogens controlling self-renewal and differentiation decisions of adult neural
stem cells. Multiciliated ependymal cells become fully differentiated at
postnatal stages however they are specified during mid to late embryogenesis from
a population of radial glial cells. Here we discuss recent findings suggesting
that 2 novel molecules, Mcidas and GemC1/Lynkeas are key players on radial glial
specification to ependymal cells. Both proteins were initially described as cell
cycle regulators revealing sequence similarity to Geminin. They are expressed in
radial glial cells committed to the ependymal cell lineage during embryogenesis,
while overexpression and knock down experiments showed that are sufficient and
necessary for ependymal cell generation. We propose that Mcidas and GemC1/Lynkeas
are key components of the molecular cascade that promotes radial glial cells fate
commitment toward multiciliated ependymal cell lineage operating upstream of c
Myb and FoxJ1.
PMID- 27606338
TI - Maintenance of neural stem cell regional identity in culture.
AB - Neural stem cells (NSCs) are distributed throughout the ventricular
subventricular zone (V-SVZ) in the adult mouse brain. NSCs located in spatially
distinct regions of the V-SVZ generate different types of olfactory bulb (OB)
neurons, and the regional expression of specific transcription factors correlates
with these differences in NSC developmental potential. In a recent article, we
show that Nkx2.1-expressing embryonic precursors give rise to NKX2.1+ NSCs
located in the ventral V-SVZ of adult mice. Here we characterize a V-SVZ
monolayer culture system that retains regional gene expression and neurogenic
potential of NSCs from the dorsal and ventral V-SVZ. In particular, we find that
Nkx2.1-lineage V-SVZ NSCs maintain Nkx2.1 expression through serial passage and
can generate new neurons in vitro. Thus, V-SVZ NSCs retain key aspects of their
in vivo regional identity in culture, providing new experimental opportunities
for understanding how such developmental patterns are established and maintained
during development.
PMID- 27606339
TI - Histone methylation, alternative splicing and neuronal differentiation.
AB - Alternative splicing, as well as chromatin structure, greatly contributes to
specific transcriptional programs that promote neuronal differentiation. The
activity of G9a, the enzyme responsible for mono- and di-methylation of lysine 9
on histone H3 (H3K9me1 and H3K9me2) in mammalian euchromatin, has been widely
implicated in the differentiation of a variety of cell types and tissues. In a
recent work from our group (Fiszbein et al., 2016) we have shown that alternative
splicing of G9a regulates its nuclear localization and, therefore, the efficiency
of H3K9 methylation, which promotes neuronal differentiation. We discuss here our
results in the light of a report from other group (Laurent et al. 2015)
demonstrating a key role for the alternative splicing of the histone demethylase
LSD1 in controlling specific gene expression in neurons. All together, these
results illustrate the importance of alternative splicing in the generation of a
proper equilibrium between methylation and demethylation of histones for the
regulation of neuron-specific transcriptional programs.
PMID- 27606340
TI - Metabotropic glutamate receptor 5: a target for migraine therapy.
AB - INTRODUCTION: Many patients suffering from migraine gain little relief from
existing treatments partly because many existing acute and preventive therapies
used in migraine have been adopted from other neurologic conditions such as
depression or epilepsy. Here, we present data supporting a new migraine-specific
target, the mGlu5 receptor. METHODS: We studied the effect of mGlu5 blockade
using ADX10059, on neuronal firing in the trigeminocervical complex (TCC) and
durovascular effects of nociceptive trigeminovascular activation in the
anesthetized rat. The clinical potential of the mGlu5 mechanism was tested with
ADX10059 orally in a double-blind placebo-controlled, parallel group, clinical
trial. RESULTS: The negative allosteric mGlu5 modulator ADX10059 attenuated dural
vasodilator responses to meningeal stimulation in a dose-dependent manner,
comparable to naratriptan, while the N-methyl-d-aspartate receptor blocker MK-801
had no effect. ADX10059 reduced responses of trigeminocervical neurons to dural
stimulation, most strikingly affecting their spontaneous firing rate.
Immunostaining identified mGlu5 and not mGlu1a receptors in the TCC. The primary
efficacy endpoint for the clinical trial, 2 h pain free, demonstrated a
significant effect of ADX10059 375 mg, 17%, versus placebo, 5%. No serious
adverse events were reported at the primary dose, with transient dizziness being
the most common treatment-emergent event at 48%. INTERPRETATION: Our findings
provide preclinical and clinical proof of concept establishing mGlu5 as a novel
therapeutic target in the treatment of migraine. Although ADX10059 is unsuitable
as a therapeutic candidate, because of hepatoxicity detected in a subsequent
study, the data open a new direction for migraine research and therapy.
PMID- 27606341
TI - Cognition in Friedreich's ataxia: a behavioral and multimodal imaging study.
AB - OBJECTIVE: Friedreich's ataxia (FRDA) is a spinocerebellar degenerative disorder,
in which cognitive deficits are sparsely explored. In this behavioral and
multimodal magnetic resonance imaging (MRI) study, we investigated the
neurocognitive profile and cortico-cerebellar dysfunctions underlying executive
functioning in individuals with FRDA. METHODS: 22 FRDA patients and 22 controls
were clinically and neuropsychologically examined. Fifteen of each underwent
structural and functional MRI using a verbal-fluency task with phonemic and
semantic conditions. Gray (GM) and white matter (WM) alterations were assessed by
means of voxel-based morphometry and diffusion-tensor imaging. RESULTS: The
neuropsychological profile demonstrated deficits in verbal fluency, working
memory and social cognition. Functional MRI data showed most pronounced group
differences in phonemic fluency with patients exhibiting enhanced activity in the
cerebellum (VI, Crus I), fronto-insular, premotor and temporo-occipital regions.
The semantic condition only revealed reduced activity in the anterior cerebellum;
for overt speech, we found increased activity in the motor cortex. Functional
connectivity-analysis showed higher co-activation within cerebellar and cortical
regions, respectively, and impaired interregional coupling between the cerebellum
and fronto-insular cortex for phonemic processing, which was also related to
poorer task performance. GM reduction in FRDA was mainly found in lobule VI,
whereas WM degeneration was more pronounced including brainstem, cerebellum, and
cortex. Decreased cerebellar GM was associated with enhanced activity in the
fronto-insular cortex, while loss of WM integrity may translate cortico
cerebellar pathway disruptions. INTERPRETATION: The pattern of increased neural
response with both cerebellar and cortical involvement underlying executive
functioning indicates functional reorganization driven by disease-related
structural damage in FRDA.
PMID- 27606342
TI - alpha-synuclein conformational antibodies fused to penetratin are effective in
models of Lewy body disease.
AB - OBJECTIVE: Progressive accumulation of alpha-synuclein (alpha-syn) has been
associated with Parkinson's disease (PD) and Dementia with Lewy body (DLB). The
mechanisms through which alpha-syn leads to neurodegeneration are not completely
clear; however, the formation of various oligomeric species have been proposed to
play a role. Antibody therapy has shown effectiveness at reducing alpha-syn
accumulation in the central nervous system (CNS); however, most of these studies
have been conducted utilizing antibodies that recognize both monomeric and higher
molecular weight alpha-syn. In this context, the main objective of this study was
to investigate the efficacy of immunotherapy with single-chain antibodies (scFVs)
against specific conformational forms of alpha-syn fused to a novel brain
penetrating sequence. METHOD: We screened various scFVs against alpha-syn
expressed from lentiviral vectors by intracerebral injections in an alpha-syn tg
model. The most effective scFVs were fused to the cell-penetrating peptide
penetratin to enhance transport across the blood-brain barrier, and lentiviral
vectors were constructed and tested for efficacy following systemic delivery
intraperitoneal into alpha-syn tg mice. RESULT: Two scFVs (D5 and 10H)
selectively targeted different alpha-syn oligomers and reduced the accumulation
of alpha-syn and ameliorated functional deficits when delivered late in disease
development; however, only one of the antibodies (D5) was also effective when
delivered early in disease development. These scFVs were also utilized in an
enzyme-linked immunosorbent assay (ELISA) assay to monitor the effects of
immunotherapy on alpha-syn oligomers in brain and plasma. INTERPRETATION: The
design and targeting of antibodies for specific species of alpha-syn oligomers is
crucial for therapeutic immunotherapy and might be of relevance for the treatment
of Lewy body disease.
PMID- 27606343
TI - Longitudinal MRI quantification of muscle degeneration in Duchenne muscular
dystrophy.
AB - OBJECTIVE: The aim of this study was to evaluate the usefulness of magnetic
resonance imaging (MRI) in detecting the progression of Duchenne muscular
dystrophy (DMD) by quantification of fat infiltration (FI) and muscle volume
index (MVI, a residual-to-total muscle volume ratio). METHODS: Twenty-six
patients (baseline age: 5-12 years) with genetically proven DMD were
longitudinally analyzed with lower limb 3T MRI, force measurements, and
functional tests (Gowers, 10-m time, North Star Ambulatory Assessment, 6-min
walking test). Five age-matched controls were also examined, with a total of 85
MRI studies. Semiquantitative (scores) and quantitative MRI (qMRI) analyses
(signal intensity ratio - SIR, lower limb MVI, and individual muscle MVI) were
carried out. Permutation and regression analyses according to both age and
functional test-outcomes were calculated. Age-related quantitative reference
curves of SIRs and MVIs were generated. RESULTS: FI was present on glutei and
adductor magnus in all patients since the age of 5, with a proximal-to-distal
progression and selective sparing of sartorius and gracilis. Patients' qMRI
measures were significantly different from controls' and among age classes. qMRI
were more sensitive than force measurements and functional tests in assessing
disease progression, allowing quantification also after loss of ambulation. Age
related curves with percentile values were calculated for SIRs and MVIs, to
provide a reference background for future experimental therapy trials. SIRs and
MVIs significantly correlated with all clinical measures, and could reliably
predict functional outcomes and loss of ambulation. INTERPRETATIONS: qMRI-based
indexes are sensitive measures that can track the progression of DMD and
represent a valuable tool for follow-up and clinical studies.
PMID- 27606344
TI - Neurofilament light chain: a biomarker for genetic frontotemporal dementia.
AB - OBJECTIVE: To evaluate cerebrospinal fluid (CSF) and serum neurofilament light
chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential
biomarker in the presymptomatic stage and during the conversion into the
symptomatic stage. Additionally, to correlate NfL levels to clinical and
neuroimaging parameters. METHODS: In this multicenter case-control study, we
investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and
86 patients with microtubule-associated protein tau (MAPT), progranulin (GRN),
and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118
subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects
both CSF and serum was determined. In two subjects CSF was available before and
after symptom onset (converters). Additionally, NfL levels were correlated with
clinical parameters, survival, and regional brain atrophy. RESULTS: CSF NfL
levels in patients (median 6762 pg/mL, interquartile range 3186-9309 pg/mL) were
strongly elevated compared with presymptomatic carriers (804 pg/mL, 627-1173
pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate
both groups. Serum NfL correlated highly with CSF NfL (r s = 0.87, P < 0.001) and
was similarly elevated in patients. Longitudinal samples in the converters showed
a three- to fourfold increase in CSF NfL after disease onset. Additionally, NfL
levels in patients correlated with disease severity, brain atrophy, annualized
brain atrophy rate and survival. INTERPRETATION: NfL in both serum and CSF has
the potential to serve as a biomarker for clinical disease onset and has a
prognostic value in genetic FTD.
PMID- 27606345
TI - Tumor prevention facilitates delayed transplant of stem cell-derived motoneurons.
AB - OBJECTIVE: Nerve injuries resulting in prolonged periods of denervation result in
poor recovery of motor function. We have previously shown that embryonic stem
cell-derived motoneurons transplanted at the time of transection into a
peripheral nerve can functionally reinnervate muscle. For clinical relevance, we
now focused on delaying transplantation to assess reinnervation after prolonged
denervation. METHODS: Embryonic stem cell-derived motoneurons were transplanted
into the distal segments of transected tibial nerves in adult mice after
prolonged denervation of 1-8 weeks. Twitch and tetanic forces were measured ex
vivo 3 months posttransplantation. Tissue was harvested from the transplants for
culture and immunohistochemical analysis. RESULTS: In this delayed reinnervation
model, teratocarcinomas developed in about one half of transplants. A residual
multipotent cell population (~ 6% of cells) was found despite neural
differentiation. Exposure to the alkylating drug mitomycin C eliminated this
multipotent population in vitro while preserving motoneurons. Treating neural
differentiated stem cells prior to delayed transplantation prevented tumor
formation and resulted in twitch and tetanic forces similar to those in animals
transplanted acutely after denervation. INTERPRETATION: Despite a neural
differentiation protocol, embryonic stem cell-derived motoneurons still carry a
risk of tumorigenicity. Pretreating with an antimitotic agent leads to survival
and functional muscle reinnervation if performed within 4 weeks of denervation in
the mouse.
PMID- 27606346
TI - Neurologic syndrome associated with homozygous mutation at MAG sialic acid
binding site.
AB - The MAG gene encodes myelin-associated glycoprotein (MAG), an abundant protein
involved in axon-glial interactions and myelination during nerve regeneration.
Several members of a consanguineous family with a clinical syndrome reminiscent
of Pelizaeus-Merzbacher disease and demyelinating leukodystrophy on brain MRI
were recently found to harbor a homozygous missense p.Ser133Arg MAG mutation.
Here, we report two brothers from a nonconsanguineous family afflicted with
progressive cognitive impairment, neuropathy, ataxia, nystagmus, and gait
disorder. Exome sequencing revealed the homozygous missense mutation p.Arg118His
in MAG. This Arg118 residue in immunoglobulin domain 1 is critical for sialic
acid binding, providing a compelling mechanistic basis for disease pathogenesis.
PMID- 27606348
TI - Erratum: GLP-1 receptor activation improves neurological outcome after murine
brain trauma 1 (9), pp 1-12.
AB - [This corrects the article DOI: 10.1002/acn3.99.].
PMID- 27606347
TI - Paraneoplastic cerebellar degeneration with anti-Yo antibodies - a review.
AB - The ataxic syndrome associated with Anti-Yo antibody, or Purkinje cell
cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic
cerebellar degeneration (PCD). The typical presentation involves the subacute
development of pancerebellar deficits with a clinical plateau within 6 months.
The vast majority of cases have been reported in women with pelvic or breast
tumors. Magnetic resonance imaging of the brain is often normal in the early
stages, with cerebellar atrophy seen later. The underlying mechanism is believed
to be an immunological reaction to cerebellar degeneration-related protein 2
(CDR2), a protein usually found in the cerebellum that is ectopically produced by
tumor cells. Although both B- and T-cell abnormalities are seen, there is debate
about the relative importance of the autoantibodies and cytotoxic T lymphocytes
in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated
protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early
stages. The low prevalence of this condition has not allowed for large-scale
randomized controlled trials. Immunotherapies, such as steroids, intravenous
immune globulins, and plasma exchange, have been extensively used in managing
this condition, with limited success. Although some reports indicate benefit from
antitumor therapies like surgery and chemotherapy, this has not been consistently
observed. The prognosis for anti-Yo PCD is almost uniformly poor, with most
patients left bedridden. Further studies are required to clarify the
pathophysiology and provide evidence-based treatment options.
PMID- 27606349
TI - Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits
choroidal neovascularization.
AB - To test the hypothesis that increased Rap1a activity specifically in retinal
pigment epithelial cells resists choroidal neovascularization (CNV), self
complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP
vectors were generated and introduced subretinally into Rap1b-deficient mice. Six
week-old mice that received subretinal control (scAAV2-Con) or constitutively
active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 * 10(8) viral
particle/ul dose 5 weeks later without altering retinal morphology or function.
Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes
injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial
(RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after
laser, comparable to eyes that received intravitreal anti-VEGF versus IgG
control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan
cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited
TNFalpha-induced disassociation of junctional pan-cadherin/beta-catenin
complexes, increased transepithelial electrical resistance through an interaction
of beta-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited
choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This
evidence shows that increased Rap1a activity specifically in RPE cells is
sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated
protection of RPE junctional complexes.
PMID- 27606350
TI - Sendai virus, an RNA virus with no risk of genomic integration, delivers
CRISPR/Cas9 for efficient gene editing.
AB - The advent of RNA-guided endonuclease (RGEN)-mediated gene editing, specifically
via CRISPR/Cas9, has spurred intensive efforts to improve the efficiency of both
RGEN delivery and targeted mutagenesis. The major viral vectors in use for
delivery of Cas9 and its associated guide RNA, lentiviral and adeno-associated
viral systems, have the potential for undesired random integration into the host
genome. Here, we repurpose Sendai virus, an RNA virus with no viral DNA phase and
that replicates solely in the cytoplasm, as a delivery system for efficient Cas9
mediated gene editing. The high efficiency of Sendai virus infection resulted in
high rates of on-target mutagenesis in cell lines (75-98% at various endogenous
and transgenic loci) and primary human monocytes (88% at the ccr5 locus) in the
absence of any selection. In conjunction with extensive former work on Sendai
virus as a promising gene therapy vector that can infect a wide range of cell
types including hematopoietic stem cells, this proof-of-concept study opens the
door to using Sendai virus as well as other related paramyxoviruses as versatile
and efficient tools for gene editing.
PMID- 27606351
TI - Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell
immunotherapy for transplant patients.
AB - Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and
BK virus are a common and predictable problem in transplant recipients. While
cellular immune therapies have been successfully used to tackle infectious
complications in transplant recipients, manufacturing immunotherapies to address
the multitude of possible pathogens can be technically challenging and labor
intensive. Here we describe a novel adenoviral antigen presentation platform (Ad
MvP) as a tool for rapid generation of multivirus-specific T-cells in a single
step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr
virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that
Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus
specific T-cells from transplant recipients and in vivo priming of antiviral T
cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr
virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP
expanded autologous and allogeneic multivirus-specific T-cells is highly
effective in controlling Epstein-Barr virus tumor outgrowth and improving overall
survival. We propose that Ad-MvP has wide ranging therapeutic applications in
greatly facilitating in vivo priming of antiviral T-cells, the generation of
third-party T-cell banks as "off-the-shelf" therapeutics as well as autologous T
cell therapies for transplant patients.
PMID- 27606353
TI - Nonfatal PML in a patient with multiple sclerosis treated with dimethyl fumarate.
PMID- 27606352
TI - Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis.
AB - OBJECTIVE: To identify circulating microRNAs (miRNAs) linked to disease stage and
disability in multiple sclerosis (MS). METHODS: Sera from 296 participants
including patients with MS, other neurologic diseases (Alzheimer disease and
amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis
and asthma) and healthy controls (HCs) were tested. miRNA profiles were
determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with
MS were categorized according to disease stage and disability. In the discovery
phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs.
Following this, significant miRNAs (p < 0.05) from the discovery set were
validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74
samples from other disease controls (Alzheimer disease, amyotrophic lateral
sclerosis, asthma, and rheumatoid arthritis). RESULTS: We validated 7 miRNAs that
differentiate patients with MS from HCs (p < 0.05 in both the discovery and
validation phase); miR-320a upregulation was the most significantly changing
serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease
progression, with miR-27a-3p being the most significant. Ten miRNAs correlated
with the Expanded Disability Status Scale of which miR.199a.5p had the strongest
correlation with disability. Of the 15 unique miRNAs we identified in the
different group comparisons, 12 have previously been reported to be associated
with MS but not in serum. CONCLUSIONS: Our findings identify circulating serum
miRNAs as potential biomarkers to diagnose and monitor disease status in MS.
CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that
circulating serum miRNAs can be used as biomarker for MS.
PMID- 27606354
TI - Distinct T cell signatures define subsets of patients with multiple sclerosis.
AB - OBJECTIVE: We investigated T cell responses to myelin proteins in the blood of
healthy controls and 2 groups of patients with relapsing-remitting multiple
sclerosis (RRMS) who exhibited lesions either predominantly in the brain or
predominantly in the spinal cord in order to assess whether distinct
neuroinflammatory patterns were associated with different myelin protein-specific
T cell effector function profiles and whether these profiles differed from
healthy controls. METHODS: Peripheral blood mononuclear cells were obtained from
patients with brain-predominant RRMS, patients with spinal cord-predominant RRMS,
and age-matched healthy controls and analyzed by enzyme-linked immunosorbent spot
assays to quantify interferon gamma-secreting (Th1) and interleukin 17-secreting
(Th17) cells responding directly ex vivo to myelin basic protein (MBP) and myelin
oligodendrocyte glycoprotein (MOG). RESULTS: Although MBP and MOG elicited
different responses, patients with multiple sclerosis (MS) who had spinal cord
predominant lesions exhibited significantly higher Th17:Th1 ratios in response to
both MBP and MOG compared to patients with brain-predominant MS. Incorporating
the cytokine responses to both antigens into logistic regression models showed
that these cytokine responses were able to provide good discrimination between
patients with distinct neuroinflammatory patterns. CONCLUSIONS: Our findings
suggest that the localization of lesions within the brain vs the spinal cord in
patients with MS is associated with different effector T cell responses to myelin
proteins. Further investigation of the relationship between T cell effector
function, antigen specificities, and lesion sites may reveal features of
pathogenic pathways that are distinct to patients with different
neuroinflammatory patterns.
PMID- 27606355
TI - Neuroleptic intolerance in patients with anti-NMDAR encephalitis.
AB - OBJECTIVE: To precisely describe the initial psychiatric presentation of patients
with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis)
to identify potential clues enhancing its early diagnosis. METHODS: We
retrospectively studied the French Reference Centre medical records of every
adult patient with anti-NMDAR encephalitis to specify the patients' initial
psychiatric symptoms leading to hospitalization in a psychiatric department and
the reasons underlying the diagnosis of anti-NMDAR encephalitis. RESULTS: The
medical records of 111 adult patients were reviewed. Psychiatric features were
the initial presentation in 65 patients (59%). Among them, several psychiatric
manifestations were observed, including visual and auditory hallucinations (n =
26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective
episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five
patients (40% of total cohort) were first hospitalized in a psychiatric
institution (91% women), with a median duration of stay of 9 days (range 0.25-239
days). Among them, 24 patients (53%) had associated discreet neurologic signs at
the first evaluation, while 17 additional patients (38%) developed neurologic
signs within a few days. Twenty-one patients (47%) were transferred to a medical
unit for a suspicion of antipsychotic intolerance characterized by high
temperature, muscle rigidity, mutism or coma, and biological results suggesting
rhabdomyolysis. CONCLUSIONS: Several psychiatric presentations were observed in
patients with anti-NMDAR encephalitis, although none was specific; however,
patients, mostly women, also had discreet neurologic signs that should be
carefully assessed as well as signs of antipsychotic intolerance that should
raise suspicion for anti-NMDAR encephalitis.
PMID- 27606356
TI - Serotonin-norepinephrine reuptake inhibitors may exacerbate stiff-person
syndrome.
PMID- 27606359
TI - The role of Australian Family Physician in supporting general practice research -
A personal perspective.
PMID- 27606357
TI - Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).
AB - OBJECTIVE: Biallelic mutations in the AP5Z1 gene encoding the AP-5 zeta subunit
have been described in a small number of patients with hereditary spastic
paraplegia (HSP) (SPG48); we sought to define genotype-phenotype correlations in
patients with homozygous or compound heterozygous sequence variants predicted to
be deleterious. METHODS: We performed clinical, radiologic, and pathologic
studies in 6 patients with biallelic mutations in AP5Z1. RESULTS: In 4 of the 6
patients, there was complete loss of AP-5 zeta protein. Clinical features
encompassed not only prominent spastic paraparesis but also sensory and motor
neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from
affected patients tested positive for periodic acid Schiff and autofluorescent
storage material, while electron microscopic analysis demonstrated lamellar
storage material consistent with abnormal storage of lysosomal material.
CONCLUSIONS: Our findings expand the spectrum of AP5Z1-associated
neurodegenerative disorders and point to clinical and pathophysiologic overlap
between autosomal recessive forms of HSP and lysosomal storage disorders.
PMID- 27606358
TI - Caregiver Abuse of Chicago Chinese Older Adults in a Community-Dwelling
Population.
AB - OBJECTIVES: This study aimed to examine the prevalence and correlates of elder
abuse reported by adult children among U.S Chinese populations. METHOD: A
community-based participatory research approach was implemented. A total of 548
Chinese adult children aged 21 years and over participated in this study. Elder
abuse reported by adult children was assessed using Caregiver Abuse Screen
(CASE). RESULTS: This study found a prevalence of 59.8%for elder abuse among 548
adult children. Younger age (r = -0.10, p < .05), higher level of education (r =
0.20, p < .001), higher income (r = 0.14, p < .01), more years in the U.S. (r =
0.12, p < .05), not born in Mainland China (r = -0.13, p < .01), and English
speaking (r = 0.16, p < .001) were positively correlated with elder abuse
reported by adult children. DISCUSSION: Elder abuse by adult children is
prevalent among U.S. Chinese populations. It is necessary for researchers, health
care providers and policy makers to put more attention on elder abuse by adult
children. Longitudinal research is needed to explore the risk factors associated
with elder abuse by adult children. Health care providers should improve
detection of elder abuse and support at-risk caregivers. Policy makers may
consider cultural sensitive approaches to address elder abuse.
PMID- 27606360
TI - The asthma enigma - how are we doing 25 years on?
PMID- 27606361
TI - The changing face of Australian general practice across the decades.
PMID- 27606362
TI - From medical gaze to statistical person: Historical reflections on evidence-based
and personalised medicine.
AB - BACKGROUND: The nineteenth century saw the rise of what historians of medicine
have termed the 'medical gaze'. Physicians used instrumentation and trained
senses to locate the site of disease within the patient's body. This change in
practice went alongside changes in the physician's power and how diseases were
understood. In the twenty-first century, the rise of high-throughput biomedical
experiments, especially in genomics, is leading to equally dramatic shifts in
medicine. Increasingly, clinical decisions may be made on the basis of data and
statistical associations rather than the particularities of the case at hand.
OBJECTIVE: The aim of this commentary iso re-evaluate the status of precision and
evidence-based medicine in light of the social, political and economic shifts
they entail. DISCUSSION: Increasingly, the statistical view of diseases and
people threatens to take judgment and expertise out of medical decision making.
It threatens the centrality of the physician in the relationship between patient
and disease.
PMID- 27606363
TI - A historical account of the doctor's bag.
AB - BACKGROUND: A household phrase of yesteryear was the doctor's 'little black bag'.
Where did this phrase come from and how did it evolve? OBJECTIVE: The objective
of the article is to outline the history of the medical bag and its contents,
from early times to the present day, by using library research methodology.
DISCUSSION: The first mention of a medical bag is in the Hippocratic Corpus
around 350 BCE. This demonstrates that since ancient times, medical practitioners
have carried some equipment and medications with them when they visited their
patients, the exact contents changing over time.
PMID- 27606364
TI - Facial hair growth in a patient with psoriasis.
PMID- 27606365
TI - Ear discomfort in a competitive surfer.
PMID- 27606366
TI - Purpuric rash in a young adult.
PMID- 27606367
TI - Traumatic nasal injuries in general practice.
AB - BACKGROUND: Traumatic nasal injuries are common in all age groups of the
community. Significant nasal trauma can cause nasal fractures and a range of
complicating injuries. OBJECTIVE: This article provides general practitioners
(GPs) with a succinct overview of pathology arising from nasal trauma, and a
framework on the assessment and management of common nasal injuries. DISCUSSION:
During assessment of traumatic nasal injuries, it is essential to exclude a
septal haematoma, which requires urgent drainage. Undisplaced nasal fractures
without functional symptoms can be managed conservatively. Displaced fractures
should be referred for reduction. There is a window of two weeks before the
displaced nasal bones start uniting. Investigations are rarely indicated for
traumatic nasal injuries. Blood tests, including full blood count and coagulation
screening, may be indicated in severe epistaxis. X-rays are not helpful for the
assessment of traumatic nasal injuries. Computed tomography (CT) scans are only
indicated if there is a suspected orbital, maxillary, frontal or zygomatic
fractures.
PMID- 27606368
TI - A pale macule and a waxy pink lesion in a child with neurofibromatosis type 1.
PMID- 27606369
TI - Falling up stairs.
PMID- 27606370
TI - Medication-related queries received for 'after hours GP helpline' - Comparison of
callers' intentions with GPs' advice.
AB - BACKGROUND: Limited studies have explored the actual usage of the 'after hours GP
helpline' (AGPH). OBJECTIVE: The objectives of the article are to describe
medication-related calls to the AGPH and compare callers' original intentions
versus the advice provided by the general practitioner (GP). METHODS: We
performed a detailed descriptive statistical analysis of medication-related
queries received by the AGPH in 2014. RESULTS: In 2014, 13,600 medication-related
calls were made to the national AGPH. For 86.56% of calls, GPs advised callers to
either self-care only, or self-care overnight and see their GP during business
hours. Of the 1442 calls where the caller had originally intended to visit the
emergency department (ED), 76.70% were advised by GPs to self-care, and only
5.48% were advised to call 000 or visit an ED. Overall, less than 2.26% of
callers were directed to the ED, despite 10.60% of people originally calling with
this intention. DISCUSSION: The availability of an after-hours service
potentially prevented 1363 people from unnecessarily attending an ED and directed
228 people who had originally underestimated the seriousness of their condition
to an ED.
PMID- 27606371
TI - Road safety risks in young people attending general practice: A cross-sectional
study of road risks and associated health risks.
AB - BACKGROUND: Young people have a large burden of death and disease from risky road
behaviours. Guidelines recommend injury prevention and harm minimisation
counselling; however, little is known about road risks in youth attending primary
care. OBJECTIVE: The aim of this study was to examine the type of road risks and
associated behaviours in young people attending general practice. METHODS: A
cross-sectional analysis was undertaken on health risk survey data from a sample
of 901 patients, aged 14-24 years, attending 40 Victorian general practices in a
stratified cluster randomised trial. RESULTS: Frequently occurring road risks
included travelling with people under the influence of alcohol or drugs (55%),
speeding (43%) and mobile phone use (40%). These behaviours were strongly
associated with other health risks, including use of tobacco, alcohol and illicit
drugs, and unprotected sex. DISCUSSION: High proportions of youth attending
general practice engage in road risks, making this a potential setting to discuss
road risks along with broader health risk prevention activities.
PMID- 27606372
TI - Can we measure integration of healthcare from administrative and clinical
records?
AB - BACKGROUND: A major component of integrated care is shared information. Computer
based clinical and administrative systems, particularly in multidisciplinary
environments, provide an opportunity to directly measure the degree of
integration. OBJECTIVE: The objective of this article is to explore the viability
of automated measurement of integration within a multidisciplinary healthcare
centre. METHODS: With the assistance of practice staff, researchers explored the
structure and content of selected patient records in two practices to understand
the viability of automated measurement. RESULTS: Extracted patient records can be
used to understand integration to the degree that communication is recorded, but
at significant expense to the practices and researchers. Automated systems are
practical to the degree that clinicians complete all relevant identifying fields.
DISCUSSION: Computerised clinical systems provide opportunities for exploring
integration of care if they include a range of care providers and all relevant
fields are always completed. The latter condition will always be difficult to
achieve.
PMID- 27606373
TI - Identification of Aboriginal and Torres Strait Islander status by general
practice registrars: Confidence and associations.
AB - BACKGROUND: Identification of Aboriginal and Torres Strait Islander status in
healthcare settings is essential for the delivery of culturally appropriate care.
Under-identification is common and practitioner confidence is a known barrier.
OBJECTIVE: The objective of this research was to document the self-reported
confidence of general practice registrars in identifying the Aboriginal and
Torres Strait Islander status of their patients, and associations of this
confidence. METHODS: This research used cross-sectional analysis of survey and
patient encounter data of general practice registrars training across five
Australian states. RESULTS: Of the 698 registrars (97.5% response rate) who
participated in the study, 74.5% had a high level of confidence in identifying a
patient's Aboriginal and Torres Strait Islander status. Older and more senior
registrars had significantly greater confidence. There was also a significant
association with the registrars' training provider. DISCUSSION: More than a
quarter of registrars reported low confidence for this basic consultation skill.
Our findings will inform general prac-tice vocational training and continuing
professional development, and reinforce the importance of a comprehensive, system
wide approach to the identification of patients' Aboriginal or Torres Strait
Islander status.
PMID- 27606374
TI - The contribution of a knowledge exchange organisation in primary healthcare.
AB - BACKGROUND: The use of relevant quality research and evidence to inform policy
and practice is complex, takes time and requires skill. Over the past 20 years, a
knowledge exchange organisation (the Primary Health Care Research and Information
Service [PHCRIS]) has developed, implemented and evaluated ways to accelerate the
use of research and evidence to strengthen Australian primary healthcare and
thereby enhance health. OBJECTIVE: This paper outlines how PHCRIS operates to
accelerate the use of research and evidence in primary healthcare policy and
practice. DISCUSSION: PHCRIS takes an integrated approach to accelerate the use
of research and evidence in primary healthcare by sharing information, research
and evidence; summarising and synthesising research; building capacity; and
facilitating knowledge exchange. Resources developed to support this approach
have a strong emphasis on access, quality, relevance and timeliness. The success
of the approach has been achieved through respectful and effective engagement
with stakeholders, extensive use of technologies and continuous quality
improvement.
PMID- 27606375
TI - Is Australia ready to implement delayed prescribing in primary care? A review of
the evidence.
AB - BACKGROUND: Antibiotic resistance is a major global public health threat. Most
antibiotic prescriptions for human consumption in primary care are for acute
respiratory tract infections (ARTIs). Australia continues to be a high prescriber
of antibiotics, compared with other Organisation for Economic Cooperation and
Development (OECD) countries. Implementation of evidence-based strategies to
reduce antibiotic use in primary care is needed. Delayed prescribing is one
evidence-based strategy that is underused. OBJECTIVE: This article describes
delayed prescribing, the evidence for its effectiveness, how it works, how it
could be implemented in Australia and what individual general practitioners (GPs)
can do. DISCUSSION: Delayed prescribing, also called 'wait-and-see prescribing',
is the process whereby a GP makes an antibiotic prescription available during the
consultation, but asks the patient to delay its use to see if symptoms will
resolve first. Evidence indicates that delayed prescribing is an effective
strategy for reducing antibiotic use but requires implementation. Individual GPs
can begin to use this strategy as a method of treating patients with ARTIs.
PMID- 27606376
TI - Clinical challenge.
AB - Questions for this month's clinical challenge are based on articles in this
issue. The clinical challenge is endorsed by the RACGP Quality Improvement and
Continuing Professional Development (QI&CPD) program and has been allocated four
Category 2 points (Activity ID:59922). Answers to this clinical challenge are
available immediately following successful completion online at
http://gplearning.racgp.org.au. Clinical challenge quizzes may be completed at
any time throughout the 2014-16 triennium; therefore, the previous months'
answers are not published. Each of the questions or incomplete statements below
is followed by four suggested answers or completions. Select the most appropriate
statement as your answer.
PMID- 27606377
TI - A mechanistic study and computational prediction of iron, cobalt and manganese
cyclopentadienone complexes for hydrogenation of carbon dioxide.
AB - A series of cobalt and manganese cyclopentadienone complexes are proposed and
examined computationally as promising catalysts for hydrogenation of CO2 to
formic acid with total free energies as low as 20.0 kcal mol-1 in aqueous
solution. Density functional theory study of the newly designed cobalt and
manganese complexes and experimentally reported iron cyclopentadienone complexes
reveals a stepwise hydride transfer mechanism with a water or a methanol molecule
assisted proton transfer for the cleavage of H2 as the rate-determining step.
PMID- 27606378
TI - Non-plasmonic metal nanoparticles as visible light photocatalysts for the
selective oxidation of aliphatic alcohols with molecular oxygen at near ambient
conditions.
AB - Nanoparticles (NPs) of Pd and Pt were used for the selective oxidation of
aliphatic alcohols with molecular oxygen as an oxidant at near ambient
temperatures under visible light irradiation. Distinct final products were
obtained under identical reaction conditions, aliphatic esters formed over the Pd
NPs while aldehydes formed over the Pt NPs. The reason for this different product
selectivity is proven to be due to the much stronger interaction of Pd NPs with
alcohol and aldehyde compared to Pt NPs. The photocatalytic activity is tuneable
by light intensity or a moderate change in the reaction temperature.
PMID- 27606379
TI - Building Momentum: Taking on the Real "Issues" of Diabetes Care!
PMID- 27606380
TI - Symptoms in Smokers with Preserved Pulmonary Function.
PMID- 27606420
TI - Potential Significance of Circular RNA in Human Placental Tissue for Patients
with Preeclampsia.
AB - AIMS: This study aimed to identify the different expression of circular RNAs
(circRNAs) in the placental tissues of pregnant women with preeclampsia (PE) and
to provide a new avenue of research regarding the pathological mechanisms of PE.
METHODS: In this study, we collected 40 placental tissues from PE patients and 35
placental tissues from gestational age-matched patients who gave premature birth.
Arraystar circRNA Microarray Technology (KANGCHEN, Shanghai, China) was used to
analyze the differential expression of circRNAs. According to the basic content
of circRNAs in the two groups and their fold changes and due to the
practicability of the designed divergent primers of each candidate circRNA, we
selected three up-regulated circRNAs, hsa_circRNA_100782, hsa_circRNA_102682 and
hsa_circRNA_104820, to validate the data. Real-time quantitative reverse
transcriptase-polymerase chain reaction (qRT-PCR) was utilized to estimate the Ct
values in both groups. We further evaluated the differences with a paired t-test
and a receiver operating characteristic (ROC) curve. RESULTS: Many circRNAs were
found to be differentially expressed in PE placental tissues versus their
controls; of these, 143 circRNAs were up-regulated and 158 were down-regulated.
The expression levels of hsa_circRNA_100782 (p < 0.05), hsa_circRNA_102682 (p <
0.05), and hsa_circRNA_104820 (p < 0.0001) were validated as significantly up
regulated in the experimental group compared with the controls. Finally, we
performed a literature comparison to forecast the possible mechanisms of circRNA
function during PE. CONCLUSION: circRNA expression significantly differed in
placental PE tissues compared with controls. According to the circRNA microarray
results and the existing papers, circRNAs may contribute to the pathogenesis of
PE by acting as miRNA sponges; this possibility requires additional investigation
in future studies.
PMID- 27606421
TI - Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8
Independent of Somatic Sex Reprogramming.
AB - The differential programming of sperm and eggs in gonads is a fundamental topic
in reproductive biology. Although the sexual fate of germ cells is believed to be
determined by signaling factors from sexually differentiated somatic cells in
fetal gonads, the molecular mechanism that determines germ cell fate is poorly
understood. Herein, we show that mothers against decapentaplegic homolog 4
(SMAD4) in germ cells is required for female-type differentiation. Germ cells in
Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo
meiotic prophase I, which coincides with the weaker expression of genes required
for follicular formation, indicating that SMAD4 signaling is essential for oocyte
differentiation and meiotic progression. Intriguingly, germline-specific deletion
of Smad4 in Stra8-null female germ cells resulted in the up-regulation of genes
required for male gonocyte differentiation, including Nanos2 and PLZF, suggesting
the initiation of male-type differentiation in ovaries. Moreover, our
transcriptome analyses of mutant ovaries revealed that the sex change phenotype
is achieved without global gene expression changes in somatic cells. Our results
demonstrate that SMAD4 and STRA8 are essential factors that regulate the female
fate of germ cells.
PMID- 27606423
TI - Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity
following Focal Cerebral Ischemia in Rats.
AB - OBJECTIVE: This study was conducted to examine the neuroprotective effects of
alpha-tocopherol against edema formation and disruption of the blood-brain
barrier (BBB) following transient focal cerebral ischemia in rats. MATERIALS AND
METHODS: Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n
= 32 in each), namely the sham, and control and alpha-tocopherol-treated (30
mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by
occlusion of the left middle cerebral artery. At the end of the 24-hour
reperfusion period, the animals were randomly selected and used for 4
investigations (n = 8) in each of the 3 main groups: (a) assessment of
neurological score and measurement of infarct size, (b) detection of brain edema
formation by the wet/dry method, (c) evaluation of BBB permeability using the
Evans blue (EB) extravasation technique, and (d) assessment of the
malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high
performance liquid chromatography methods. RESULTS: Induction of cerebral
ischemia in the control group produced extensive brain edema (brain water content
83.8 +/- 0.11%) and EB leakage into brain parenchyma (14.58 +/- 1.29 ug/g) in
conjunction with reduced GSH and elevated MDA levels (5.86 +/- 0.31 mmol/mg and
63.57 +/- 5.42 nmol/mg, respectively). Treatment with alpha-tocopherol
significantly lowered brain edema formation and reduced EB leakage compared with
the control group (p < 0.001, 80.1 +/- 0.32% and 6.66 +/- 0.87 ug/g,
respectively). Meanwhile, treatment with alpha-tocopherol retained tissue GSH
levels and led to a lower MDA level (p < 0.01, 10.17 +/- 0.83 mmol/mg, and p <
0.001, 26.84 +/- 4.79 nmol/mg, respectively). CONCLUSION: Treatment with alpha
tocopherol reduced ischemic edema formation and produced protective effects on
BBB function following ischemic stroke occurrence. This effect could be through
increasing antioxidant activity.
PMID- 27606422
TI - Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and
Neurochemical Studies in C57BL/6 Mice.
AB - Dermatosis often as a chronic disease requires effective long-term treatment; a
comprehensive evaluation of mental health of dermatology drug does not receive
enough attention. An interaction between dermatology and psychiatry has been
increasingly described. Substantial evidence has accumulated that psychological
stress can be associated with pigmentation, endocrine and immune systems in skin
to create the optimal responses against pathogens and other physicochemical
stressors to maintain or restore internal homeostasis. Additionally, given the
common ectodermal origin shared by the brain and skin, we are interested in
assessing how disruption of skin systems (pigmentary, endocrine and immune
systems) may play a key role in brain functions. Thus, we selected three drugs
(hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to
respectively intervene in these systems and then evaluate the potential
neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of
hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%,
respectively, 5 times of the clinical dose). Behavioral testing was performed and
levels of proteins were measured in the hippocampus. It was found that mice
treated with isotretinoin or tacrolimus, presented a lower activity in open-field
test and obvious depressive-like behavior in tail suspension test. Besides, they
damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and
increased the expression of apoptosis-related proteins in the hippocampus. To
enable sensitive monitoring the dose-response characteristics of the consecutive
neurobehavioral disorders, mice received gradient concentrations of hydroquinone
(2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and
hippocampal dysfunction in a dose-dependent response. When doses were high as 6%
which was 3 times higher than 2% dose, then 100% of mice exhibited depressive
like behavior. Certainly, 6% hydroquinone exposure elicited the most serious
impairment of hippocampal structure and survival. The fact that higher doses of
hydroquinone are associated with a greater risk of depression is further
indication that hydroquinone is responsible for the development of depression.
These above data demonstrated that chronic administration of different
dermatology drugs contributed into common mental distress. This surprising
discovery of chemical stressors stimulating the hippocampal dysfunction, paves
the way for exciting areas of study on the cross-talk between the skin and the
brain, as well as is suggesting how to develop effective and safe usage of
dermatological drugs in daily practice.
PMID- 27606424
TI - Intravaginal Chlamydia trachomatis Challenge Infection Elicits TH1 and TH17
Immune Responses in Mice That Promote Pathogen Clearance and Genital Tract
Damage.
AB - While ascension of Chlamydia trachomatis into the upper genital tract of women
can cause pelvic inflammatory disease and Fallopian tube damage, most infections
elicit no symptoms or overt upper genital tract pathology. Consistent with this
asymptomatic clinical presentation, genital C. trachomatis infection of women
generates robust TH2 immunity. As an animal model that modeled this response
would be invaluable for delineating bacterial pathogenesis and human host
defenses, herein we explored if pathogen-specific TH2 immunity is similarly
elicited by intravaginal (ivag) infection of mice with oculogenital C.
trachomatis serovars. Analogous to clinical infection, ascension of primary C.
trachomatis infection into the mouse upper genital tract produced no obvious
tissue damage. Clearance of ivag challenge infection was mediated by interferon
(IFN)-gamma-producing CD4+ T cells, while IFN-gamma signaling blockade
concomitant with a single ivag challenge promoted tissue damage by enhancing
Chlamydia-specific TH17 immunity. Likewise, IFN-gamma and IL-17 signaling
blockade or CD4+ T cell depletion eliminated the genital pathology produced in
untreated controls by multiple ivag challenge infections. Conversely, we were
unable to detect formation of pathogen-specific TH2 immunity in C. trachomatis
infected mice. Together, our work revealed C. trachomatis infection of mice
generates TH1 and TH17 immune responses that promote pathogen clearance and
immunopathological tissue damage. Absence of Chlamydia-specific TH2 immunity in
these mice newly highlights the need to identify experimental models of C.
trachomatis genital infection that more closely recapitulate the human host
response.
PMID- 27606425
TI - Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin
Resistance in Leishmania major.
AB - BACKGROUND: Tubercidin (TUB) is a toxic adenosine analog with potential
antiparasitic activity against Leishmania, with mechanism of action and
resistance that are not completely understood. For understanding the mechanisms
of action and identifying the potential metabolic pathways affected by this drug,
we employed in this study an overexpression/selection approach using TUB for the
identification of potential targets, as well as, drug resistance genes in L.
major. Although, TUB is toxic to the mammalian host, these findings can provide
evidences for a rational drug design based on purine pathway against
leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: After transfection of a cosmid
genomic library into L. major Friedlin (LmjF) parasites and application of the
overexpression/selection method, we identified two cosmids (cosTUB1 and cosTU2)
containing two different loci capable of conferring significant levels of TUB
resistance. In the cosTUB1 contained a gene encoding NUPM1-like protein, which
has been previously described as associated with TUB resistance in L.
amazonensis. In the cosTUB2 we identified and characterized a gene encoding a 63
kDa protein that we denoted as tubercidin-resistance protein (TRP). Functional
analysis revealed that the transfectants were less susceptible to TUB than LmjF
parasites or those transfected with the control vector. In addition, the trp mRNA
and protein levels in cosTUB2 transfectants were higher than LmjF. TRP
immunolocalization revealed that it was co-localized to the endoplasmic reticulum
(ER), a cellular compartment with many functions. In silico predictions indicated
that TRP contains only a hypothetical transmembrane domain. Thus, it is likely
that TRP is a lumen protein involved in multidrug efflux transport that may be
involved in the purine metabolic pathway. CONCLUSIONS/SIGNIFICANCE: This study
demonstrated for the first time that TRP is associated with TUB resistance in
Leishmania. The next challenge is to determine how TRP mediates TUB resistance
and whether purine metabolism is affected by this protein in the parasite.
Finally, these findings may be helpful for the development of alternative anti
leishmanial drugs that target purine pathway.
PMID- 27606426
TI - Spatial Scaling of the Profile of Selective Attention in the Visual Field.
AB - Neural mechanisms of selective attention must be capable of adapting to variation
in the absolute size of an attended stimulus in the ever-changing visual
environment. To date, little is known regarding how attentional selection
interacts with fluctuations in the spatial expanse of an attended object. Here,
we use event-related potentials (ERPs) to investigate the scaling of attentional
enhancement and suppression across the visual field. We measured ERPs while
participants performed a task at fixation that varied in its attentional demands
(attentional load) and visual angle (1.0 degrees or 2.5 degrees ). Observers
were presented with a stream of task-relevant stimuli while foveal, parafoveal,
and peripheral visual locations were probed by irrelevant distractor stimuli. We
found two important effects in the N1 component of visual ERPs. First, N1
modulations to task-relevant stimuli indexed attentional selection of stimuli
during the load task and further correlated with task performance. Second, with
increased task size, attentional modulation of the N1 to distractor stimuli
showed a differential pattern that was consistent with a scaling of attentional
selection. Together, these results demonstrate that the size of an attended
stimulus scales the profile of attentional selection across the visual field and
provides insights into the attentional mechanisms associated with such spatial
scaling.
PMID- 27606427
TI - Molecular Evolutionary Pathways toward Two Successful Community-Associated but
Multidrug-Resistant ST59 Methicillin-Resistant Staphylococcus aureus Lineages in
Taiwan: Dynamic Modes of Mobile Genetic Element Salvages.
AB - Clonal complex 59 (CC59) Staphylococcus aureus in Taiwan includes both
methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus
(MRSA). As the most prominent community-associated MRSA (CA-MRSA) in Taiwan, CC59
has two major clones characterized as PVL-negative SCCmec IV (carrying the
staphylococcal cassette chromosome mec IV but Panton-Valentine leukocidin
negative) and PVL-positive SCCmec V (5C2&5). We investigated the drug resistance,
phylogeny and the distribution and sequence variation of SCCmec, staphylococcal
bacteriophage phiSA3, genomic island nuSabeta and MES (an enterococcal mobile
genetic element conferring multidrug resistance) in 195 CC59 S. aureus.
Sequencing and PCR mapping revealed that all of the CC59/SCCmec V (5C2&5) MRSA
strains had acquired MESPM1 or its segregants, and obtained a phiSA3-related
fragment in nuSabeta. In contrast, MES6272-2 and MES4578, which showed gentamicin
resistance that was not encoded by MESPM1, were dominant in SCCmec IVg MRSA.
Translocation of a whole phiSA3 into nuSabeta instead of only a phiSA3-related
fragment was common in SCCmec IVg MRSA. However, the non-subtype-g SCCmec IV MRSA
(SCCmec IVa is the major) still carried MES and nuSabeta structures similar to
those in SCCmec V (5C2&5) MRSA. A minimum spanning tree constructed by multiple
locus variable-number tandem repeat analysis revealed that SCCmec IVg MRSA and
SCCmec V (5C2&5) MRSA grouped respectively in two major clades. The CC59 MSSA was
equally distributed among the two clades, while the non-subtype-g SCCmec IV MRSA
mostly clustered with SCCmec V (5C2&5) MRSA. Our findings strongly suggest that
CC59 MSSA acquired divergent mobile genetic elements and evolved to SCCmec IVg
MRSA and SCCmec V (5C2&5) MRSA/non-subtype-g SCCmec IV MRSA independently. The
evolutionary history of CC59 S. aureus explains how mobile genetic elements
increase the antimicrobial resistance and virulence and contribute to the success
of CA-MRSA in Taiwan.
PMID- 27606428
TI - The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR,
Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A
Pharmacogenetics Study.
AB - OBJECTIVES: Warfarin oral anticoagulant therapy (OAT) requires regular and
frequent drug adjustment monitored by INR. Interindividual variability, drug and
diet interferences, and genetics (VKORC1 and CYP2C9) make the
maintenance/reaching of stable INR a not so easy task. HPLC assessment of
warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but
definite results are still lacking. We evaluated possible correlations between
INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel
alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was
performed to account for the known influence on warfarin homeostasis. METHODS:
133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin
serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52
patients were monitored in detail (5 consecutive controls; c0-c4) till the target
INR was reached. Correlation analyses were performed in both groups. RESULTS: In
the whole OAT group both warfarin and 3'-hydroxywarfarin correlate with INR at
comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin
weekly dosage better correlates with warfarin than with 3'-hydroxywarfarin (r2 =
0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3'
hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001).
Interestingly, 3'-hydroxywarfarin reached a strong correlation at c4 respect to
warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively)
seeming less affected by drug adjustments in the subgroup of 52 patients who
started OAT. The multivariate analyses aimed at estimating the true contribution
of 3'-hydroxywarfarin on INR value ascribed it the unique significant value (p =
0.0021) in spite of warfarin who lost association. The pharmacogenetics studies
confirmed that patients carrying the VKORC1 variant-allele required lower
warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded
a warfarin responsive index (WRI) inversely related to the number variant
alleles. CONCLUSION: Our results overall suggest that 3'-hydroxywarfarin
monitoring could be of great advantage in INR monitoring respect to classical
warfarin assessment showing significant contribution also in multivariate
analysis. Therefore, additional active metabolites should be recognized and
investigated as novel useful indicators.
PMID- 27606430
TI - Identification of Heme Oxygenase-1 as a Novel Predictor of Hematopoietic Stem
Cell Transplantation Outcomes in Acute Leukemia.
AB - OBJECTIVE: The main aim of this study was to determine the correlation between
clinical outcome and heme oxygenase-1 (HO-1) expression before and after
hematopoietic stem cell transplantation (HSCT) in acute leukemia. METHODS: HO-1
mRNA levels in 83 patients were measured using qRT-PCR. In a comparative analysis
of HO-1 levels in relation to different post-transplant outcomes, the HO-1
threshold, determined via the receiver operating characteristic (ROC) curve, was
effectively used to predict clinical relapse and acute graft-versus-host disease
(aGVHD). The correlations among clinical relapse, aGVHD and HO-1 expression were
analyzed based on this threshold. RESULTS: Leukemia risk stratification and
relative expression of HO-1 before pretreatment had significant effects on
clinical relapse. Leukemia risk stratification, relative expression of HO-1 after
HSCT and the interval from diagnosis to transplantation had a significant
influence on aGVHD. Both relapse and aGVHD appeared to be associated with
relative HO-1 expression. The relative expression rate of HO-1 was 1.131-1.186
before pretreatment, and strongly associated with post-transplantation relapse.
The relative expression rate of HO-1 was 1.102-1.144 after transplantation, and
closely related to aGVHD. ROC curve analysis revealed high specificity and
sensitivity of HO-1 expression in predicting relapse and aGVHD after allo-HSCT.
CONCLUSIONS: HO-1 expression can be effectively used as a predictor of relapse as
well as a diagnostic factor of aGVHD after transplantation for allo-HSCT patients
with acute leukemia.
PMID- 27606429
TI - Single Nucleotide Polymorphism Discovery in Bovine Pituitary Gland Using RNA-Seq
Technology.
AB - Examination of bovine pituitary gland transcriptome by strand-specific RNA-seq
allows detection of putative single nucleotide polymorphisms (SNPs) within
potential candidate genes (CGs) or QTLs regions as well as to understand the
genomics variations that contribute to economic trait. Here we report a breed
specific model to successfully perform the detection of SNPs in the pituitary
gland of young growing bulls representing Polish Holstein-Friesian (HF), Polish
Red, and Hereford breeds at three developmental ages viz., six months, nine
months, and twelve months. A total of 18 bovine pituitary gland polyA
transcriptome libraries were prepared and sequenced using the Illumina NextSeq
500 platform. Sequenced FastQ databases of all 18 young bulls were submitted to
NCBI-SRA database with NCBI-SRA accession numbers SRS1296732. For the
investigated young bulls, a total of 113,882,3098 raw paired-end reads with a
length of 156 bases were obtained, resulting in an approximately 63 million
paired-end reads per library. Breed-wise, a total of 515.38, 215.39, and 408.04
million paired-end reads were obtained for Polish HF, Polish Red, and Hereford
breeds, respectively. Burrows-Wheeler Aligner (BWA) read alignments showed
93.04%, 94.39%, and 83.46% of the mapped sequencing reads were properly paired to
the Polish HF, Polish Red, and Hereford breeds, respectively. Constructed breed
specific SNP-db of three cattle breeds yielded at 13,775,885 SNPs. On an average
765,326 breed-specific SNPs per young bull were identified. Using two stringent
filtering parameters, i.e., a minimum 10 SNP reads per base with an accuracy >=
90% and a minimum 10 SNP reads per base with an accuracy = 100%, SNP-db records
were trimmed to construct a highly reliable SNP-db. This resulted in a reduction
of 95,7% and 96,4% cut-off mark of constructed raw SNP-db. Finally, SNP
discoveries using RNA-Seq data were validated by KASPTM SNP genotyping assay. The
comprehensive QTLs/CGs analysis of 76 QTLs/CGs with RNA-seq data identified
KCNIP4, CCSER1, DPP6, MAP3K5 and GHR CGs with highest SNPs hit loci in all three
breeds and developmental ages. However, CAST CG with more than 100 SNPs hits were
observed only in Polish HF and Hereford breeds.These findings are important for
identification and construction of novel tissue specific SNP-db and breed
specific SNP-db dataset by screening of putative SNPs according to QTL db and
candidate genes for bovine growth and reproduction traits, one can develop
genomic selection strategies for growth and reproductive traits.
PMID- 27606431
TI - All-Atom Molecular Dynamics Reveals Mechanism of Zinc Complexation with
Therapeutic F10.
AB - Advancing the use of therapeutic nucleic acids requires understanding the
chemical and structural properties that allow these polymers to promote the death
of malignant cells. Here we explore Zn2+ complexation by the fluoropyrimidine
polymer F10, which has strong activities in multiple preclinical models of
cancer. Delivery of fluoropyrimidine FdUMP in the 10-residue polymer F10 rather
than the nucleobase (5-fluorouracil) allows consideration of metal ion binding
effects on drug delivery. The differences in metal ion interactions with
fluoropyrimidine compared to normal DNA results in conformation changes that
affect protein binding, cell uptake, and codelivery of metals such as zinc, and
the cytoxicity thereof. Microsecond-time-scale, all-atom simulations of F10
predict that zinc selectively stabilizes the polymer via interactions with
backbone phosphate groups and suggest a mechanism of complexation for the zinc
base interactions shown in previous experimental work. The positive zinc ions are
attracted to the negatively charged phosphate groups. Once the Zn2+ ions are near
F10, they cause the base's N3 nitrogen to deprotonate. Subsequently, magnesium
atoms displace zinc from their interactions with phosphate, freeing the zinc ions
to interact with the FdU bases by forming weak interactions with the O4 oxygen
and the fluorine attached to C5. These interactions of magnesium with phosphate
groups and zinc with nucleobases agree with previous experimental results and are
seen in MD simulations only when magnesium is introduced after N3 deprotonation,
indicating a specific order of metal binding events. Additionally, we predict
interactions between zinc and F10's O2 atoms, which were not previously observed.
By comparison to 10mers of polyU and polydT, we also predict that the presence of
fluorine increases the binding affinity of zinc to F10 relative to analogous
strands of RNA and DNA consisting of only native nucleotides.
PMID- 27606432
TI - Exposures among MERS Case-Patients, Saudi Arabia, January-February 2016.
PMID- 27606433
TI - Critical appraisal of European LeukemiaNet (ELN) 2013 recommendations for the
management of chronic myeloid leukemia: is it early for a warning?
PMID- 27606434
TI - 3D bioprinting of skin: a state-of-the-art review on modelling, materials, and
processes.
AB - The skin is the largest organ of the body, having a complex multi-layered
structure and guards the underlying muscles, bones, ligaments, and internal
organs. It serves as the first line of defence to any external stimuli, hence it
is the most vulnerable to injury and warrants the need for rapid and reliable
regeneration methods. Tissue engineered skin substitutes help overcome the
limitations of traditional skin treatment methods, in terms of technology, time,
and cost. While there is commendable progress in the treating of superficial
wounds and injuries with skin substitutes, treatment of full-thickness injuries,
especially with third or fourth degree burns, still looks murkier. Engineering
multi-layer skin architecture, conforming to the native skin structure is a
tougher goal to achieve with the current tissue engineering methods, if not
impossible, restoring all the functions of the native skin. The testing of drugs
and cosmetics is another area, where engineered skins are very much needed, with
bans being imposed on product testing on animals. Given this greater need, 3D
bioprinting is a promising technology that can achieve rapid and reliable
production of biomimetic cellular skin substitutes, satisfying both clinical and
industrial needs. This paper reviews all aspects related to the 3D bioprinting of
skin, right from imaging the injury site, 3D model creation, biomaterials that
are used and their suitability, types of cells and their functions, actual
bioprinting technologies, along with the challenges and future prospects.
PMID- 27606435
TI - The Increasing Incidence of Melanoma: It May Be More Than a Freckle.
PMID- 27606437
TI - Health-related Quality of Life in Children and Adolescents With beta-Thalassemia
Major on Different Iron Chelators in Basra, Iraq.
AB - Few studies have investigated the quality of life of children with thalassemia in
the Middle East or Mediterranean region, especially Iraq. Therefore, this study
was performed to assess the health-related quality of life (HRQoL) of patients
with beta-thalassemia major compared with healthy children and adolescents in the
same age group and to evaluate the effects of different iron chelators on HRQoL
measurements. A case-control study was performed on patients with beta
thalassemia major registered at the Center for Hereditary Blood Diseases in Basra
from February 2012 through July 2013. The group included children and adolescents
aged 2 to 17 years old. HRQoL was assessed using the Pediatric Quality of Life
(PedsQL) Generic Core Scale questionnaire, version 4.0, for children 2 to 12
years old and the Short Form-36 health survey questionnaire, version 2 (SF-36v2),
for children and adolescents aged 13 to 17 years old. A total of 209 age-matched
and sex-matched children and adolescents were included in the control group. The
study did not find a significant difference in PedsQL scores among different age
groups or different iron chelators, whereas there were significant differences in
all of the SF-36v2 domains, with the best quality of life observed in the
deferasirox group, followed by the deferoxamine group and the combined therapy
group (P<0.05). The use of deferasirox among patients aged 13 to 17 years old was
associated with higher SF-36v2 scores than in the other groups (P<0.05). However,
for younger patients, the PedsQL scores were not significantly different for
different iron chelators. The use of oral deferasirox significantly improved the
quality of life of adolescents with beta-thalassemia major. However, this effect
was less prominent among patients aged 2 to 12 years old.
PMID- 27606436
TI - A Comparison of Hemostatic Changes in Splenectomized and Nonsplenectomized beta
Thalassemia Intermedia Patients.
AB - The present study was conducted to compare the coagulation factors between
splenectomized and nonsplenectomized thalassemia intermedia (TI) patients as well
as a healthy control group. A total of 60 splenectomized and 60 nonsplenectomized
TI patients and 60 healthy controls participated in this case-control study. The
level of homocysteine, protein C and S, antithrombin III, factors V and VIII,
fibrinogen, and D-dimer were measured in all groups. Our results indicated a
significant reduction of protein C and S and fibrinogen in TI patients compared
with healthy controls (P<0.001), as well as factor V activity (P=0.009). Also a
significant elevation of D-dimer (P=0.006) and factor VIII activity (P=0.001) was
observed. There was no significant difference considering homocysteine and
antithrombin III level among patients and healthy controls. Also our results
demonstrated that there was no significant difference considering the homeostatic
parameters (except D-dimer activity) between splenectomized and nonsplenectomized
TI patients after adjustment for age. In conclusion, reduction of protein C and
S, fibrinogen, and factor V activity and elevation of D-dimer levels and factor
VIII activity was observed in TI patients compared with healthy controls. It
seems that splenectomy has little significant effect on concentration of
hemostatic factors except for D-dimer activity.
PMID- 27606438
TI - Vitamin D Receptor (VDR) Polymorphisms in Pediatric Patients Presenting With
Hodgkin's Lymphoma.
AB - Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor
types than in healthy individuals, suggesting that some polymorphisms (Cdx2,
Fok1, Bsm1, Apa1, Taq1) contribute to tumor development. There is no previous
report on VDR polymorphism in Hodgkin's lymphoma (HL) patients. VDR polymorphism
patterns in 95 pediatric HL cases with 100 healthy controls were compared. No
statistically significant difference was found between the patient group and
control group in terms of Cdx2, Fok1, Bsm1, Apa1, and Taq1 polymorphisms (P>0.5).
Our findings suggest that VDR polymorphisms may not play a role in HL
development.
PMID- 27606439
TI - The suicidality continuum in a large sample of obsessive-compulsive disorder
(OCD) patients.
AB - BACKGROUND: Obsessive-compulsive disorder (OCD) has a chronic course leading to
huge impact in the patient's functioning. Suicidal thoughts and attempts are much
more frequent in OCD subjects than once thought before. AIM: To empirically
investigate whether the suicidal phenomena could be analyzed as a suicidality
severity continuum and its association with obsessive-compulsive (OC) symptom
dimensions and quality of life (QoL), in a large OCD sample. METHODS: Cross
sectional study with 548 patients diagnosed with OCD according to the DSM-IV
criteria, interviewed in the Brazilian OCD Consortium (C-TOC) sites. Patients
were evaluated by OCD experts using standardized instruments including: Yale
Brown Obsessive-Compulsive Scale (YBOCS); Dimensional Yale-Brown Obsessive
Compulsive Scale (DYBOCS); Beck Depression and Anxiety Inventories; Structured
Clinical Interview for DSM-IV (SCID); and the SF-36 QoL Health Survey. RESULTS:
There were extremely high correlations between all the suicidal phenomena. OCD
patients with suicidality had significantly lower QoL, higher severity in the
"sexual/religious", "aggression" and "symmetry/ordering" OC symptom dimensions,
higher BDI and BA scores and a higher frequency of suicide attempts in a family
member. In the regression analysis, the factors that most impacted suicidality
were the sexual dimension severity, the SF-36 QoL Mental Health domain, the
severity of depressive symptoms and a relative with an attempted suicide history.
CONCLUSIONS: Suicidality could be analyzed as a severity continuum and patients
should be carefully monitored since they present with suicidal ideation. Lower
QoL scores, higher scores on the sexual dimension and a family history of suicide
attempts should be considered as risk factors for suicidality among OCD patients.
PMID- 27606441
TI - Off the grid.
PMID- 27606442
TI - CRISPR mouse model boom, rat model renaissance.
PMID- 27606443
TI - Strata rolls out drug-matching service, offers free tumor profiling.
PMID- 27606444
TI - Combined insulin/GLP-1 pens near market.
PMID- 27606445
TI - Human-animal hybrid ban may end soon.
PMID- 27606440
TI - Applications of CRISPR technologies in research and beyond.
AB - Programmable DNA cleavage using CRISPR-Cas9 enables efficient, site-specific
genome engineering in single cells and whole organisms. In the research arena,
versatile CRISPR-enabled genome editing has been used in various ways, such as
controlling transcription, modifying epigenomes, conducting genome-wide screens
and imaging chromosomes. CRISPR systems are already being used to alleviate
genetic disorders in animals and are likely to be employed soon in the clinic to
treat human diseases of the eye and blood. Two clinical trials using CRISPR-Cas9
for targeted cancer therapies have been approved in China and the United States.
Beyond biomedical applications, these tools are now being used to expedite crop
and livestock breeding, engineer new antimicrobials and control disease-carrying
insects with gene drives.
PMID- 27606446
TI - Jounce checkpoint lures Celgene.
PMID- 27606447
TI - Farmers' microbe aid.
PMID- 27606448
TI - Merck stakes out 'irritable' neuron territory with $1.25 billion.
PMID- 27606449
TI - Setbacks rattle allergy vaccine frontrunners, but hopes remain.
PMID- 27606450
TI - Around the world in a month.
PMID- 27606451
TI - A spark at the periphery.
PMID- 27606452
TI - Where the bodies lie.
PMID- 27606453
TI - The impact of personal genomics on risk perceptions and medical decision-making.
PMID- 27606454
TI - Containment of transgenic trees by suppression of LEAFY.
PMID- 27606456
TI - Recent patents in antimicrobials and infectious disease.
PMID- 27606455
TI - Which patent and where? Why international patent transparency by companies is
needed for medicines.
PMID- 27606457
TI - Super-resolution microscopy writ large.
PMID- 27606458
TI - Precision medicine for autoimmune disease.
PMID- 27606460
TI - Alighting on soft robot rays.
PMID- 27606461
TI - A survival guide for interdisciplinary PhD students.
PMID- 27606463
TI - [Beweggrunde von Krebspatienten fur und gegen die Inanspruchnahme der
Misteltherapie].
AB - Einleitung: Die Misteltherapie ist im deutschsprachigen Raum ein haufig
angewandtes komplementarmedizinisches Verfahren (KM) in der Onkologie. Diese
Studie hatte das Ziel, die Beweggrunde fur oder gegen eine Inanspruchnahme der
Misteltherapie zu untersuchen und Themenfeldern zuzuordnen. Patienten und
Methoden: Es wurden qualitative leitfadengestutzte Interviews mit Krebspatienten
gefuhrt. Der Interviewleitfaden fragte nach der Inanspruchnahme von KM, der
Motivation zur Inanspruchnahme, Informationsverhalten und -bedurfnissen zu KM
sowie nach der Krebserkrankung. Um die Beweggrunde fur die Inanspruchnahme oder
Nichtinanspruchnahme der Misteltherapie zu verstehen, wurden die Interviews
inhaltsanalytisch ausgewertet. Ergebnisse: Insgesamt wurden Interviews mit 88
Krebspatienten gefuhrt, davon nutzen 18 (20,5%) die Misteltherapie. Die
Beweggrunde fur oder gegen eine Inanspruchnahme der Misteltherapie liebetaen sich
den 2 Themenfeldern "Wahrgenommene Indikation" und "Abwagungen bei der
Entscheidungsfindung" zuordnen. Diskussion und Schlussfolgerungen: Mit der
Misteltherapie wird sowohl ein Einfluss auf das Tumorwachstum als auch eine
supportive Wirkung assoziiert. Anwender sehen die Misteltherapie als sicheres
Verfahren; Nichtnutzer befurchten eher Neben- oder Wechselwirkungen. Die
Empfehlung von Fachpersonal spielt eine wichtige Rolle bei der Inanspruchnahme.
Zum Teil waren die Nichtnutzer interessiert an der Anwendung der Misteltherapie,
befanden sich jedoch noch im Klarungsprozess.
PMID- 27606464
TI - LANA-Mediated Recruitment of Host Polycomb Repressive Complexes onto the KSHV
Genome during De Novo Infection.
AB - One of the hallmarks of the latent phase of Kaposi's sarcoma-associated
herpesvirus (KSHV) infection is the global repression of lytic viral gene
expression. Following de novo KSHV infection, the establishment of latency
involves the chromatinization of the incoming viral genomes and recruitment of
the host Polycomb repressive complexes (PRC1 and PRC2) to the promoters of lytic
genes, which is accompanied by the inhibition of lytic genes. However, the
mechanism of how PRCs are recruited to the KSHV episome is still unknown.
Utilizing a genetic screen of latent genes in the context of KSHV genome, we
identified the latency-associated nuclear antigen (LANA) to be responsible for
the genome-wide recruitment of PRCs onto the lytic promoters following infection.
We found that LANA initially bound to the KSHV genome right after infection and
subsequently recruited PRCs onto the viral lytic promoters, thereby repressing
lytic gene expression. Furthermore, both the DNA and chromatin binding activities
of LANA were required for the binding of LANA to the KSHV promoters, which was
necessary for the recruitment of PRC2 to the lytic promoters during de novo KSHV
infection. Consequently, the LANA-knockout KSHV could not recruit PRCs to its
viral genome upon de novo infection, resulting in aberrant lytic gene expression
and dysregulation of expression of host genes involved in cell cycle and
proliferation pathways. In this report, we demonstrate that KSHV LANA recruits
host PRCs onto the lytic promoters to suppress lytic gene expression following de
novo infection.
PMID- 27606465
TI - Correction: Bee Venom for the Treatment of Parkinson Disease - A Randomized
Controlled Clinical Trial.
AB - [This corrects the article DOI: 10.1371/journal.pone.0158235.].
PMID- 27606466
TI - RAIDD Mediates TLR3 and IRF7 Driven Type I Interferon Production.
AB - BACKGROUND/AIMS: Viral infections represent a global health problem with the need
for new viral therapies and better understanding of the immune response during
infection. The most immediate and potent anti-viral defense mechanism is the
production of type I interferon (IFN-I) which are activated rapidly following
recognition of viral infection by host pathogen recognition receptors (PRR). The
mechanisms of innate cellular signaling downstream of PRR activation remain to be
fully understood. In the present study, we demonstrate that CASP2 and RIPK1
domain-containing adaptor with death domain (CRADD/RAIDD) is a critical component
in type I IFN production. METHODS: The role of RAIDD during IFN-I production was
investigated using western blot, shRNA mediated lentiviral knockdown,
immunoprecipitation and IFN-I driven dual luciferase assay. RESULTS:
Immunoprecipitation analysis revealed the molecular interaction of RAIDD with
interferon regulatory factor 7 (IRF7) and its phosphorylating kinase IKKepsilon.
Using an IFN-4alpha driven dual luciferase analysis in RAIDD deficient cells,
type I IFN activation by IKKepsilon and IRF7 was dramatically reduced.
Furthermore, deletion of either the caspase recruitment domain (CARD) or death
domain (DD) of RAIDD inhibited IKKepsilon and IRF7 mediated interferon-4alpha
activation. CONCLUSION: We have identified that the adaptor molecule RAIDD
coordinates IKKepsilon and IRF7 interaction to ensure efficient expression of
type I interferon.
PMID- 27606468
TI - Understanding the Association Between Relative Sociability Prototypes and
University Students' Drinking Intention.
AB - BACKGROUND: Evaluations of "the prototypical nondrinker" and of "the prototypical
regular drinker" have been demonstrated to hold associations with more harmful
drinking behavior, yet the extent to which the relative evaluation of these
prototypes is associated with drinking intention remains to be tested.
OBJECTIVES: To explore whether relatively unfavorable nondrinker prototypes are
associated with increased drinking intention and whether this relationship is
moderated by personality variables. METHODS: Among a student sample (n = 543),
alcohol-related sociability prototype measures were used to compute an index of
the perceived sociability of regular drinkers relative to nondrinkers ("relative
sociability prototypes"). Measures of drinking intention, conscientiousness,
extraversion and sensation seeking impulsivity were also taken. RESULTS: Most
students perceived the prototypical nondrinker unfavorably relative to the
prototypical regular drinker (91%, n = 493). Simple slopes analyses indicated
that extraversion moderated the strength of the relationship between relative
sociability prototypes and drinking intention such that relatively negative
evaluations of nondrinkers were only associated with increased intention to get
drunk among more extraverted students. CONCLUSIONS/IMPORTANCE: Prospective data
and behavioral measures are needed to substantiate these findings, which suggest
links between relative evaluations of nondrinkers, harmful drinking intention and
personality traits. Evidence suggests that by challenging prejudicial beliefs
concerning nondrinkers (as "unsociable") and by targeting more extraverted
students, safer drinking plans might be encouraged.
PMID- 27606467
TI - Overexpression of Large-Conductance Calcium-Activated Potassium Channels in Human
Glioblastoma Stem-Like Cells and Their Role in Cell Migration.
AB - Glioblastomas (GBMs) are brain tumors characterized by diffuse invasion of cancer
cells into the healthy brain parenchyma, and establishment of secondary foci. GBM
cells abundantly express large-conductance, calcium-activated potassium (BK)
channels that are thought to promote cell invasion. Recent evidence suggests that
the GBM high invasive potential mainly originates from a pool of stem-like cells,
but the expression and function of BK channels in this cell subpopulation have
not been studied. We investigated the expression of BK channels in GBM stem-like
cells using electrophysiological and immunochemical techniques, and assessed
their involvement in the migratory process of this important cell subpopulation.
In U87-MG cells, BK channel expression and function were markedly upregulated by
growth conditions that enriched the culture in GBM stem-like cells (U87-NS).
Cytofluorimetric analysis further confirmed the appearance of a cell
subpopulation that co-expressed high levels of BK channels and CD133, as well as
other stem cell markers. A similar association was also found in cells derived
from freshly resected GBM biopsies. Finally, transwell migration tests showed
that U87-NS cells migration was much more sensitive to BK channel block than U87
MG cells. Our data show that BK channels are highly expressed in GBM stem-like
cells, and participate to their high migratory activity. J. Cell. Physiol. 232:
2478-2488, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27606469
TI - Investigator initiated trials in Portuguese rheumatology.
PMID- 27606470
TI - [Home based and group based exercise programs in patients with ankylosing
spondylitis: systematic review].
AB - INTRODUCTION: Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic
disease characterized by inflammation of the joints of the spine and sacroiliac
and to a lesser percentage of the peripheral joints. It is a debilitating
condition which reduces quality of life in patients with AS. The practice of
physical therapy is recommended as non-pharmacological treatment as well as the
treatment and prevention of associated deformities. OBJECTIVE: To collect and
summarize the available evidence in scientific databases to realize the
effectiveness of home based and group based programs in patients with AS.
METHODS: Systematic review, where articles for the study were collected from
scientific database PubMed. We have found 65 articles with publication date
between January 1, 2004 and January 31, 2014. Inclusion and exclusion criteria
were established to make the selection of articles to include in the study. All
investigators provided their agreement in presencial meeting for a final
selection, and at a later stage, the articles were read in full by the three
investigators. RESULTS: The present systematic review includes eight randomized
controlled trials. All articles show functional benefits in patients with AS
subject to exercise programs in group based and / or home based. From the eight
articles, 4 addressed programs conducted in home based context and 4 addressed in
group based context programs. CONCLUSION: There appears to be evidence that the
programs carried out based on group are more effective than those home based
conducted in patients with AS. It was concluded also be advantageous to carry out
home based exercise programs than the absence of any exercise program.
.
PMID- 27606471
TI - Recommendations for Vaccination in Adult Patients with Systemic Inflammatory
Rheumatic Diseases from the Portuguese Society of Rheumatology.
AB - BACKGROUND: Serious infections are a major cause of morbidity and mortality in
systemic inflammatory rheumatic disease (SIRD) patients. Although vaccination may
prevent numerous infections, vaccination uptake rates are low in this group of
patients. OBJECTIVES: To develop evidence-based recommendations for vaccination
in SIRD patients. METHODS: We searched MEDLINE (until 31 October 2014) and EMBASE
(until 14 December 2014) databases, as well as the ACR and EULAR congress
abstracts (2011-2014). Patients with any systemic inflammatory rheumatic disease
were included and all vaccines were considered. Any safety and efficacy outcomes
were admitted. Search results were submitted to title and abstract selection,
followed by detailed review of suitable studies. Data were subsequently pooled
according to the type of vaccine and the SIRD considered. Results were presented
and discussed by a multidisciplinary panel and systematic literature review (SLR)
derived recommendations were voted according to the Delphi method. The level of
agreement among rheumatologists was assessed using an online survey. RESULTS:
Eight general and seven vaccine-specific recommendations were formulated.
Briefly, immunization status should routinely be assessed in all SIRD patients.
The National Vaccination Program should be followed and some additional vaccines
are recommended. To maximize the efficacy of vaccination, vaccines should
preferably be administered 4 weeks before starting immunosuppression or, if
possible when disease activity is controlled. Non-live vaccines are safe in SIRD,
including immunosuppressed patients. The safety of live attenuated vaccines in
immunosuppressed patients deserves further ascertainment, but might be considered
in particular situations. DISCUSSION: The present recommendations combine
scientific evidence with the multidisciplinary expertise of our taskforce panel
and attained desirable agreement among Portuguese rheumatologists. Vaccination
recommendations need to be updated on a regular basis, as more scientific data
regarding vaccination efficacy and safety, emergent infectious threats, new
vaccines as well as new immunomodulatory therapies become available.
PMID- 27606472
TI - Impaired myocardial deformation in psoriatic arthritis patients assessment by
speckle tracking echocardiography.
AB - OBJECTIVE: We aimed to evaluate left ventricular (LV) mechanics of patients
diagnosed with PsA and no clinical evidence for cardiovascular disease (CVD)
using a novel, more sensitive technique which evaluates myocardial deformation in
multidimensional planes for the detection of impaired LV function. METHODS: The
study enrolled 31 PsA patients and sex-age matched 19 healthy controls. All
participants underwent conventional echocardiography and 2-dimensional speckle
tracking echocardiography (STE). Global longitudinal, circumferential, and radial
strain were measured. RESULTS: Although patients with PsA had normal LV ejection
fraction, the myocardial deformation in multidimensional planes was impaired. STE
analysis results showed that PsA patients had significantly lower global
longitudinal strain (mean+/-S.D. -17.11+/-2.83 % and -19.29+/-2 % respectively,
p=0.005), global circumferential strain (mean+/-S.D. -14.28+/-3 % and -20.34+/
4.78 % respectively p<0.001) and global radial strain (mean+/-S.D. 29.26+/-10 %
and 46.54+/-17 % respectively, p<0.001) versus control group. However, no
correlation was found between longitudinal, radial, and circumferential strains
and disease-related risk factors. CONCLUSION: Subclinical impaired myocardial
deformation was common in patients with PsA even with no clinical evidence for
CVD. Thus, the use of this novel imaging technique could provide additional
benefits for determining cardiovascular involvement at an early stage and risk
stratification in PsA patients.
PMID- 27606473
TI - Association between severe disease course and nephritis with Q222R polymorphism
in DNAse I gene among lupus patients: An Argentine multicenter study.
AB - Objetives: Systemic lupus erythematosus is a multifactorial autoimmune disease
and the glomerulonephritis is one of the most severe complications, which leads
to severe persistent proteinuria, chronic renal failure, and end-stage renal
disease. This multicenter study investigated the genetic associations of a non
synonymous single-nucleotide polymorphism in DNase I with the risk of lupus and
its influence on development of nephropathy in an Argentinean population.
METHODS: Using the Polymerase chain reaction restriction fragment length
polymorphism method, the Q222R (+2373A->G; Gln244Arg) DNase I polymorphism was
studied in 156 systemic lupus erythematosus patients and 170 healthy controls.
RESULTS: Although no significant association between Q222R polymorphism and the
risk of systemic lupus erythematosus was found, the presence of the A allele was
associated with an increased risk for the development of nephropathy (p=0.019,
Odd Ratio=2.196, 95 % confidence interval [1.135-4.247]) and a worse disease
course [moderate disease course: p=0.006, Odd Ratio=3.250, 95% confidence
interval (1.401-7.539); severe disease course: p=0.040, Odd Ratio=2.339, 95%
confidence interval (1.040-5.260)]. CONCLUSIONS: A better understanding of the
genetic basis of systemic lupus erythematosus will help in the development of new
and more effectives strategies for the treatment of the disease in the future.
PMID- 27606474
TI - Thenar muscles H reflex in patients with fibromyalgia: A case control study.
AB - OBJECTIVE: To delineate H-reflex parameters and specify the diagnostic accuracy
measures of thenar muscle H-reflex in Fibromyalgia (FM). METHODS: The study was a
cross sectional study performed on 30 subjects with FM and 30 healthy volunteers
in two major referral hospitals. We recorded the number of obtainable thenar H
reflexes and their minimum latency, threshold and amplitude in each group.
RESULTS: There was a significantly more chance to elicit the H-reflex in patients
with FM. H reflex threshold and minimum latency were lower in FM group but no
significant difference was shown for H wave amplitude. According to our study,
thenar H-reflex has 46.7% sensitivity, 86.7% specificity and 66.7% diagnostic
accuracy to detect FM. It also has moderate predictive values and positive
likelihood ratio but low negative likelihood ratio. CONCLUSION: Higher rate of
thenar muscle H-reflex in fibromyalgia can be interpreted as a confirmatory
finding to central sensitization theory for this disorder. Obtaining H-reflex
from thenar muscles could be a helpful diagnostic tool for fibromyalgia that
increases the confidence in diagnosis. Although it is a weak tool for screening
because of low sensitivity, it has a relatively high specificity.
PMID- 27606475
TI - Association study of single nucleotide polymorphisms of IL23R and IL17 in
rheumatoid arthritis in the Algerian population.
AB - OBJECTIVE: Previous studies implicated that IL17/IL23 pathway and TH17 cells play
an important role in autoimmune inflammation. Genome wide association studies
have identified multiple single nucleotide polymorphisms (SNPs) in the IL23R and
IL17 genes region associated with rheumatoid arthritis (RA). METHODS: In this
study, we investigated the association of IL23R, IL17A and IL17F genes SNPs with
RA susceptibility in the Algerian population. 343 patients with RA and 323
healthy subjects were genotyped for IL23R (rs11209026, rs1343151, rs10489629),
IL17F (rs763780, rs2397084) and IL17A (rs2275913) variants by TaqMan technology.
RESULTS: There was no evidence of a genetic association between IL23R, IL17F and
IL17A SNPs and RA susceptibility in our population. However, IL23R rs1343151
variant enhanced the development of RF IgM and IgG positive (+) RA as compared
with RF IgM and IgG negative (-) RA (OR 2.29, p = 0.004 and OR 0.64, p = 0.014
respectively). Also, IL23R rs10489629 was associated with all RF isotypes
positive disease (IgM+: OR 2.16, p = 0,006; IgG+: OR 0.64, p = 0,004 and IgA+: OR
1.54, p = 0,013). A moderate association of IL17A rs2275913 with RF IgA- RA
subgroup was shown (OR 1.95, p = 0,039). Moreover, our data showed a correlation
between IL23R and IL17F variants and the parameters of disease activity such as
HAQ score and disease duration. CONCLUSION: The current study emphasizes the lack
of association of IL23R and IL17 polymorphisms with RA susceptibility in the
Algerian population. However, the data showed the relationship between IL23R and
IL17A polymorphisms and the production of the different RF isotypes in RA
patients.
PMID- 27606476
TI - Chronic skin lichenification as unusual presentation of eosinophilic
granulomatosis with polyangitis: case report and literature review.
AB - Eosinophilic granulomatosis with polyangitis (EGPA) is an uncommon ANCA
associated systemic small-vessel necrotizing vasculitis. At times, EGPA
presenting manifestations can be very different from the usually recognized
disease patterns. We report a 52-year-old female patient with 3 years history of
itching. During the time occurred a chronic skin lichenification on her legs and
gradually developed a full-blown ANCA-MPO positive EGPA in combination with blood
hypereosinophilia, eosinophilic vasculitis at skin biopsy, subclinical asthma and
chronic rhinosinusitis.
PMID- 27606477
TI - Juvenile dermatomyositis with anti-signal recognition particle antibodies: a case
report.
AB - Serologic investigation has been explored in inflammatory myopathies in order to
define subgroups that can help us predict clinical course, treatment and
prognosis. The level of similarity between juvenile and adult myopathies
regarding the presence of myositis-specific autoantibodies has not been fully
elucidated. We report the case of a 8-year-old girl who presented with a rapid
progression of muscle weakness and cutaneous signs consistent with the diagnosis
of juvenile dermatomyositis and whose serologic testing revealed the presence of
anti-signal recognition particle (SRP) antibodies. So far these antibodies have
been described mostly in adult subsets, frequently associated with poorer
outcomes and rarely related to cutaneous manifestations. The knowledge of the
degree of overlap between paediatric and adult SRP positive myopathies may
improve the medical care we provide to these children.
PMID- 27606478
TI - The use of the color Doppler ultrasonography in the diagnosis and monitoring of
an atypical case of giant-cell arteritis.
AB - Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically
characterised by headache, scalp tenderness, jaw claudication and visual
disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a
sensitive and non-invasive image technique used in the diagnosis of this disease.
This work highlights the importance of CDUS in the diagnostic workup of GCA and
also demonstrates it's usefullness in the evaluation and documentation of the
response to corticosteroids therapy in an atypical case of ACG.
PMID- 27606479
TI - Chronic recurrent multifocal osteomyelitis with isolated spinal involvement.
PMID- 27606480
TI - Spondylodiscitis (Andersson lesion) in psoriatic spondyloarthritis: a rare event
successfully treated with an anti-TNF therapy.
AB - Spondylodiscitis (Andersson lesion) is an infrequent and late complication of
advanced ankilosing arthritis. Scanty data on the efficacy of anti-TNF therapy
for these lesions are available. To our knowledge, only few cases of
spondylodiscitis occurring in patients with psoriatic arthritis were reported in
literature. We describe the case of a patient with psoriatic arthritis who early
developed Andersson lesions successfully treated with infliximab plus
methotrexate therapy.
PMID- 27606481
TI - An unusual case report of gingival overgrowth associated with the use of
leflunomide.
AB - Leflunomide is an immunomodulatory agent with antiproliferative activity that is
used for the treatment of rheumatoid arthritis. Leflunomide induced side effects
are hepatotoxicity, immunosuppression, skin reactions, peripheral neuropathy,
hypertension, diarrhea, interstitial lung disease, and rarely oral mucosal
lesions. Here, we presented an unusual case of gingival overgrowth associated
with the use of leflunomide, which improved after ceasing the drug.
PMID- 27606482
TI - Comparing Laser Peripheral Iridotomy to Cataract Extraction in Narrow Angle Eyes
Using Anterior Segment Optical Coherence Tomography.
AB - PURPOSE: To evaluate the changes in anterior chamber angle (ACA) parameters in
primary angle closure (PAC) spectrum eyes before and after cataract extraction
(CE) and compare to the changes after laser peripheral iridotomy (LPI) using
anterior segment optical coherence tomography (ASOCT). METHODS: Twenty-eight PAC
spectrum eyes of 18 participants who underwent CE and 34 PAC spectrum eyes of 21
participants who underwent LPI were included. ASOCT images with 3-dimensional
mode angle analysis scans were taken with the CASIA SS-1000 (Tomey Corp., Nagoya,
Japan) before and after CE or LPI. Mixed-effect model analysis was used to 1)
compare best-corrected visual acuity, intraocular pressure, and ACA parameters
before and after CE; 2) identify and estimate the effects of potential
contributing factors affecting changes in ACA parameters; and 3) compare CE and
LPI treatment groups. RESULTS: The increase in average angle parameters (TISA750
and TICV750) was significantly greater after CE than LPI. TICV750 increased by
102% (2.114 [+/-1.203] MUL) after LPI and by 174% (4.546 [+/- 1.582] MUL) after
CE (P < 0.001). Change of TICV750 in the CE group was significantly affected by
age (P = 0.002), race (P = 0.006), and intraocular lens power (P = 0.037).
CONCLUSIONS: CE results in greater anatomic changes in the ACA than LPI in PAC
spectrum eyes. ASOCT may be used to follow anatomic changes in the angle after
intervention.
PMID- 27606483
TI - Use of Alleviating Maneuvers for Periocular Facial Dystonias.
AB - Importance: Patients with benign essential blepharospasm or hemifacial spasm are
known to use botulinum toxin injections and alleviating maneuvers to help control
their symptoms. The clinical correlates between the use of botulinum toxin
injections and the use of alleviating maneuvers are not well established.
Objective: To determine whether the use of alleviating maneuvers for benign
essential blepharospasm or hemifacial spasm correlates with disease severity or
botulinum toxin treatment. Design, Setting, and Participants: A prospective cross
sectional observational study (designed in September 2013) of 74 patients with
benign essential blepharospasm and 56 patients with hemifacial spasm who were
consecutively recruited from adnexal clinics at Moorfields Eye Hospital (January
June 2014) to complete a questionnaire and undergo a clinical review. Data
analysis was performed in December 2015. Main Outcomes and Measures: Prevalence
and type of alleviating maneuvers used for blepharospasm and hemifacial spasm,
dystonia severity, and dose and frequency of botulinum toxin injections. Results:
Of the 74 patients with blepharospasm, 39 (52.7%) used alleviating maneuvers
(mean [SD] age, 70.4 [9.1] years); of the 56 patients with hemifacial spasm, 25
(44.6%) used alleviating maneuvers (mean [SD] age, 66.5 [12.7] years). The most
commonly used maneuver was the touching of facial areas (35 of 64 patients
[54.7%]); other maneuvers included covering the eyes (6 of 64 patients [9.4%]),
singing (5 of 64 patients [7.8%]), and yawning (5 of 64 patients [7.8%]).
Patients with blepharospasm who used alleviating maneuvers scored higher on the
Jankovic Rating Scale (median score, 5 vs 4; Hodges-Lehmann median difference, 1
[95% CI, 0-2]; P = .01) and the Blepharospasm Disability Index severity score
(median score, 11 vs 4; Hodges-Lehmann median difference, 4 [95% CI, 1-7]; P =
.01) than patients with blepharospasm who did not use alleviating maneuvers.
Patients with hemifacial spasm who used alleviating maneuvers scored higher on
the 7-item Hemifacial Spasm Quality of Life scale (median score, 7 vs 3; Hodges
Lehmann median difference, 4 [95% CI, 1-7]; P = .01) and the SMC Severity Grading
Scale (median score, 2 vs 2; Hodges-Lehmann median difference, 0 [95% CI, 0-1]; P
= .03) than patients with hemifacial spasm who did not use alleviating maneuver.
The severity of dystonia correlated with botulinum toxin treatment for patients
with blepharospasm (r = 0.23; P = .049) and patients with hemifacial spasm (r =
0.45; P = .001). There was no difference found in botulinum toxin treatment
between patients who used alleviating maneuvers and those who did not, in either
the blepharospasm group (150 vs 125 units; Hodges-Lehmann median difference, 20
units [95% CI, -10 to 70 units]; P = .15) or the hemifacial spasm group (58 vs 60
units; Hodges-Lehmann median difference, 0 units [95% CI, -15 to 20 units]; P =
.83). Conclusions and Relevance: Half of the patients with periocular facial
dystonias used alleviating maneuvers. Their use was associated with more severe
disease but not with increased use of botulinum toxin. This may help to guide
future therapies, such as advice on maneuver augmentation or tailored devices.
PMID- 27606484
TI - Extended monolayer of cyano-ended oligo(para-phenylenes) at the air/HOPG
interface investigated by high-resolution AFM.
AB - The formation of functional networks on surfaces is one of the main challenges in
the field of nanotechnologies. In this paper, we shall propose a very simple
process which can be used to achieve the formation of extended monolayer of
functional oligo(para-phenylenes) molecules at the air/graphite interface. By
developing a convergent strategy, we successfully achieved the synthesis of
oligo(para-phenylenes) molecules with a tuneable length. The photophysical
properties of these new oligomers were characterized by UV-vis absorption and
fluorescence spectroscopy. Deposition of these molecules by a simple spin-coating
process on a highly oriented pyrolytic graphite (HOPG) surface leads to the
formation of extended monolayered 2D networks. These networks were characterized
by atomic force microscopy experiments under ambient conditions with submolecular
resolution thus providing the adsorption model of these molecules on an HOPG
surface.
PMID- 27606485
TI - Olivine anisotropy suggests Gutenberg discontinuity is not the base of the
lithosphere.
AB - Tectonic plates are a key feature of Earth's structure, and their behavior and
dynamics are fundamental drivers in a wide range of large-scale processes. The
operation of plate tectonics, in general, depends intimately on the manner in
which lithospheric plates couple to the convecting interior. Current debate
centers on whether the transition from rigid lithosphere to flowing asthenosphere
relates to increases in temperature or to changes in composition such as the
presence of a small amount of melt or an increase in water content below a
specified depth. Thus, the manner in which the rigid lithosphere couples to the
flowing asthenosphere is currently unclear. Here we present results from
laboratory-based torsion experiments on olivine aggregates with and without melt,
yielding an improved database describing the crystallographic alignment of
olivine grains. We combine this database with a flow model for oceanic upper
mantle to predict the structure of the seismic anisotropy beneath ocean basins.
Agreement between our model and seismological observations supports the view that
the base of the lithosphere is thermally controlled. This model additionally
supports the idea that discontinuities in velocity and anisotropy, often assumed
to be the base of the lithosphere, are, instead, intralithospheric features
reflecting a compositional boundary established at midocean ridges, not a
rheological boundary.
PMID- 27606487
TI - Rylene and Rylene Diimides: Comparison of Theoretical and Experimental Results
and Prediction for High-Rylene Derivatives.
AB - Low rylene (R) and rylene diimides (RD) are important organic semiconductors and
dyes. High R and RD with larger conjugated cores show different properties
compared with their low counterparts. Herein, absorption spectra, frontier
molecular orbitals, band gaps, inner-sphere reorganization energy (lambdai),
ionization potential, electron affinity, and atomic charge population of 20
rylene compounds were calculated by the density functional theory method. The
theoretical results agree well with experimental ones. We predict some unusual
properties of some high rylene derivatives that are unknown compounds due to
synthetic difficulties. The lowest unoccupied molecular orbital energy levels of
RD compounds change slightly, from -3.61 to -3.79 eV, which makes them strong
electron acceptors. The band gaps narrow with the size increase of conjugated
cores, which makes high rylene derivatives near-infrared dyes. The rising highest
occupied molecular orbital energy levels of high rylene derivatives makes them
unstable in the air. The lambdai falls with the size increase of the conjugated
core, and the size of RD-4 or R-4 is big enough for the small lambdai to favor
charge transport. The charge population analysis indicates R and RD have
different charge distribution under the effect of electron-withdrawing imide
groups, which contributes to distinct properties.
PMID- 27606488
TI - Characterization of the Microbial Diversity and Chemical Composition of Gouda
Cheese Made by Potential Probiotic Strains as an Adjunct Starter Culture.
AB - This study characterized the microbial diversity and chemical properties of Gouda
cheese made by probiotics during ripening periods. Lactobacillus plantarum H4
(H4) and Lactobacillus fermentum H9 (H9), which demonstrate probiotic properties
and bioactivity, were used as adjunct starter cultures. Gouda cheese made with H4
(GCP1) and H9 (GCP2) demonstrated the highest production of formic acid and
propionic acid, respectively. Moreover, the bacterial diversity, including
richness and evenness of nonstarter lactic acid bacteria (NSLAB), increased in
probiotic cheeses. Specifically, Lactobacillus, Leuconostoc, and Streptococcaceae
were present at higher concentrations in probiotic cheeses than in control Gouda
cheese (GCC). The proportion of H4 in GCP1 increased and culminated at 1.76%,
whereas H9 in GCP2 decreased during ripening. Peptide profiles were altered by
the addition of probiotics and included various bioactive peptides. In
particular, three peptide fragments are newly detected. Therefore, Gouda cheese
could be used as an effective probiotic carrier for H4 and H9.
PMID- 27606486
TI - An alternative mode of CD43 signal transduction activates pro-survival pathways
of T lymphocytes.
AB - CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it
transduces activation signals through its cytoplasmic domain, contributing to
modulation of the outcome of T-cell responses. The aim of this study was to
uncover new signalling pathways regulated by this sialomucin. Analysis of changes
in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an
enzyme of the glycolytic pathway, as an element potentially participating in the
signalling cascade resulting from the engagement of CD43 and the T-cell receptor
(TCR). We found that the glycolytic activity of this enzyme was not significantly
increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine
phosphorylated, suggesting that it was performing moonlight functions. We report
that phosphorylation of both Y105 of PKM2 and of Y705 of signal transducer and
activator of transcription 3 was induced in response to TCR+CD43 co-stimulation,
resulting in activation of the mitogen-activated protein kinase kinase
5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP
response element binding protein (CREB) were activated, and c-Myc and nuclear
factor-kappaB (p65) nuclear localization, as well as Bad phosphorylation, were
augmented. Consistent with this, expression of human CD43 in a murine T-cell
hybridoma favoured cell survival. Altogether, our data highlight novel signalling
pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43
in promoting cell survival through non-glycolytic functions of metabolic enzymes.
PMID- 27606490
TI - Sustainable Development Goals and Telemedicine.
PMID- 27606489
TI - Acute stress alters individual risk taking in a time-dependent manner and leads
to anti-social risk.
AB - Decision-making processes can be modulated by stress, and the time elapsed from
stress induction seems to be a crucial factor in determining the direction of the
effects. Although current approaches consider the first post-stress hour a
uniform period, the dynamic pattern of activation of the physiological stress
systems (i.e., the sympathetic nervous system and hypothalamic-pituitary-adrenal
axis) suggests that its neurobehavioural impact might be heterogeneous. Here, we
evaluate economic risk preferences on the gain domain (i.e., risk aversion) at
three time points following exposure to psychosocial stress (immediately after,
and 20 and 45 min from onset). Using lottery games, we examine decisions at both
the individual and social levels. We find that risk aversion shows a time
dependent change across the first post-stress hour, evolving from less risk
aversion shortly after stress to more risk averse behaviour at the last testing
time. When risk implied an antisocial outcome to a third party, stressed
individuals showed less regard for this person in their decisions. Participants'
cortisol levels explained their behaviour in the risk, but not the antisocial,
game. Our findings reveal differential stress effects in self- and other
regarding decision-making and highlight the multidimensional nature of the
immediate aftermath of stress for cognition.
PMID- 27606491
TI - Surgical Scholarship and Research.
PMID- 27606492
TI - Marijuana use and service utilization among adolescents 7 years post substance
use treatment.
AB - BACKGROUND: In an environment of increasingly liberal attitudes towards marijuana
use and legalization, little is known about long-term trajectories of marijuana
use among clinical samples of adolescents, and how these trajectories relate to
health services utilization over time. METHODS: Latent growth curve analysis was
used to identify distinct trajectories of marijuana use in a clinical sample of
adolescents (N=391) over 7 years post substance use treatment in an integrated
health system. We examined psychiatric problems and polysubstance use associated
with the identified trajectory groups using general linear models. Nonlinear
mixed-effects logistic regressions were used to examine associations between
health services use and the trajectory groups. RESULTS: We identified three
marijuana use trajectory groups: (1) Abstinent (n=117); (2) Low/Stable use
(n=174); and (3) Increasing use (n=100). Average externalizing and
anxiety/depression scores were significantly lower over time for the Abstinent
group compared to the Increasing and Low/Stable groups. The Low Stable and the
Increasing group had fewer psychiatric visits over time (p<0.05) and the
Low/Stable group used more substance use treatment services over time compared
with the Abstinent group (p<0.001). CONCLUSIONS: Treated adolescents showed
distinct marijuana use patterns, one of which indicated a group of adolescents at
risk of increased use over time. These individuals have greater psychiatric and
polysubstance use over time, but may not be accessing needed services.
PMID- 27606493
TI - Pemphigoid gestationis: a successful preventive treatment by rituximab.
PMID- 27606494
TI - Graphical analysis of mammalian cell adhesion in vitro.
AB - Short-term (<2h) cell adhesion kinetics of 3 different mammalian cell types: MDCK
(epithelioid), MC3T3-E1 (osteoblastic), and MDA-MB-231 (cancerous) on 7 different
substratum surface chemistries spanning the experimentally-observable range of
water wettability (surface energy) are graphically analyzed to qualitatively
elucidate commonalities and differences among cell/surface/suspending media
combinations. We find that short-term mammalian cell attachment/adhesion in vitro
correlates with substratum surface energy as measured by water adhesion tension,
tau=gammalvcostheta, where gammalv is water liquid-vapor interfacial energy (72.8
mJ/m2) and costheta is the cosine of the advancing contact angle subtended by a
water droplet on the substratum surface. No definitive functional relationships
among cell-adhesion kinetic parameters and tau were observed as in previous work,
but previously-observed general trends were reproduced, especially including a
sharp transition in the magnitude of kinetic parameters from relatively low-to
high near tau=0mJ/m2, although the exact adhesion tension at which this
transition occurs is difficult to accurately estimate from the current data set.
We note, however, that the transition is within the hydrophobic range based on
the tau=30mJ/m2 surface-energetic dividing line that has been proposed to
differentiate "hydrophobic" surfaces from "hydrophilic". Thus, a rather sharp
hydrophobic/hydrophilic contrast is observed for cell adhesion for disparate
cell/surface combinations.
PMID- 27606495
TI - Molecule structural factors influencing the loading of flavoring compounds in a
natural-preformed capsule: Yeast cells.
AB - Yeast cells are efficient microcapsules for the encapsulation of flavoring
compounds. However, as they are preformed capsules, they have to be loaded with
the active. Encapsulation efficiency is to a certain level correlated with LogP.
In this study, the effect of structural factors on the encapsulation of
amphiphilic flavors was investigated. Homological series of carboxylic acids,
ethyl esters, lactones, alcohols and ketones were encapsulated into the yeast
Yarrowia lipolytica. Although, in a single homological series, the length of the
molecule and thus the LogP were correlated with encapsulation efficiency (EY%),
big differences were observable between series. For instance, carboxylic acids
and lactones exhibited EY% around 45%-55%, respectively, for compounds bigger
than C8 and C6, respectively, whereas ethyl esters reached only about 15-20% for
C10 compounds. For a group of various C6-compounds, EY% varied from 4% for
hexanal to 45% for hexanoic acid although the LogP of the two compounds was
almost similar at 1.9. In total our results point out the importance of the level
of polarity and localization of the polar part of the compound in addition to the
global hydrophobicity of the molecule. They will be of importance to optimize the
encapsulation of mixtures of compounds.
PMID- 27606497
TI - Potential application of tissue engineering for the reconstruction of facial
bones.
PMID- 27606496
TI - Monolayers of the HSA dimer on polymeric microparticles-electrokinetic
characteristics.
AB - Human serum albumin dimer (dHSA) enhances the accumulation and retention of anti
tumor drugs. In this work, monolayers of dHSA on polystyrene microparticles were
prepared and thoroughly characterized. The changes in the electrophoretic
mobility of microparticles upon the addition of controlled amounts of dHSA were
measured using Laser Doppler Velocimetry (LDV) technique. These dependencies were
quantitatively interpreted in terms of the 3D electrokinetic model. This allowed
to determine the coverage of dHSA on microparticles under in situ conditions.
Additionally, the maximum coverage of dHSA was precisely determined by the
concentration depletion method. At physiological ionic strength, the maximum
coverage of dHSA monolayer on microparticles was 1.05mg m-2. This agrees with the
theoretical value predicted from the random sequential adsorption approach by
assuming a side-on orientation of molecules. A high stability of the monolayers
under pH cycling was confirmed, which proved irreversibility of the protein
adsorption on the microparticles. The obtained results can be exploited to
prepare and characterize polymeric drug-capsule conjugated with albumin dimer.
PMID- 27606498
TI - Intradialytic hypotension.
AB - PURPOSE OF REVIEW: This review focuses on recent advances in our understanding of
intradialytic hypotension (IDH) and measures that may reduce its frequency.
RECENT FINDINGS: The frequency and severity of IDH predict the risk for adverse
clinical outcomes. The highest mortality risks associated with IDH were observed
when the intradialytic systolic blood pressure (SBP) nadirs were <90 and <100
mmHg and the predialysis SBP were <=159 mmHg or >=160 mmHg, respectively.
Interdialytic weight gain (IDWG) >=3 kg occurs more frequently among patients
with IDH. Prolonged and possibly more frequent dialysis, use of biofeedback
devices, dialysate cooling and limiting sodium loading are useful measures to
reduce the frequency of IDH. SUMMARY: Frequent IDH is associated with high IDWGs
and a poor prognosis. Studies on prolonged dialysis, biofeedback devices and
cooled dialysate have yielded promising results. Intradialytic relative blood
volume monitoring devices have been investigated in preventing IDH but results
are mixed. Administration of a sodium/hydrogen exchange isoform 3 inhibitor
increases stool sodium but has not been shown to decrease IDWG. IDH continues to
be a significant dialysis complication deserving of further investigation.
PMID- 27606500
TI - Problems on the back of an envelope.
AB - Claims that magnetic fields can be used to manipulate biological systems
contradict some basic laws of physics.
PMID- 27606501
TI - Development and validation of a high performance liquid chromatography
quantification method of levo-tetrahydropalmatine and its metabolites in plasma
and brain tissues: application to a pharmacokinetic study.
AB - Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal
herbs of the Corydalis and Stephania genera. It has been used in China for more
than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its
extensive use, its metabolism has not been quantitatively studied, nor there a
sensitive reliable bioanalytical method for its quantification simultaneously
with its metabolites. As such, the objective of this study was to develop and
validate a sensitive and selective HPLC method for simultaneous quantification of
l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP)
in rat plasma and brain tissues. Rat plasma and brain samples were processed by
liquid-liquid extraction using ethyl acetate. Chromatographic separation was
achieved on a reversed-phase Symmetry(r) C18 column (4.6 * 150 mm, 5 MUm) at 25
degrees C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium
phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The
column eluent was monitored at excitation and emission wavelengths of 230 and 315
nm, respectively. The calibration curves were linear over the concentration range
of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated
accuracy and precision within the acceptance criteria of bioanalytical
guidelines. The validated HPLC method was successfully applied to analyze samples
from a pharmacokinetic study of l-THP in rats. Taken together, the developed
method can be applied for bioanalysis of l-THP and its metabolites in rodents and
potentially can be transferred for bioanalysis of human samples.
PMID- 27606499
TI - Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6
and common BMP2 alleles.
AB - Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000
newborns, is treated surgically in infancy to prevent adverse neurologic
outcomes. To identify mutations contributing to common non-syndromic midline
(sagittal and metopic) craniosynostosis, we performed exome sequencing of 132
parent-offspring trios and 59 additional probands. Thirteen probands (7%) had
damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP -
induced osteoblast differentiation (p<10-20). SMAD6 mutations nonetheless showed
striking incomplete penetrance (<60%). Genotypes of a common variant near BMP2
that is strongly associated with midline craniosynostosis explained nearly all
the phenotypic variation in these kindreds, with highly significant evidence of
genetic interaction between these loci via both association and analysis of
linkage. This epistatic interaction of rare and common variants defines the most
frequent cause of midline craniosynostosis and has implications for the genetic
basis of other diseases.
PMID- 27606502
TI - Non-Sedated Rapid Volumetric Proton Density MRI Predicts Neonatal Brachial Plexus
Birth Palsy Functional Outcome.
AB - BACKGROUND AND PURPOSE: The current prognostic biomarker of functional outcome in
brachial plexus birth palsy is serial clinical examination throughout the first 6
months of age. This can delay surgical treatment and prolong parental anxiety in
neonates who will recover spontaneously. A potentially superior biomarker is a
volumetric proton density MRI performed at clinical presentation and within the
first 12 weeks of life, providing a high spatial and contrast resolution
examination in 4 minutes. METHODS: Nine neonates ranging in age from 4 to 9 weeks
who presented with brachial plexus birth palsy were enrolled. All subjects
underwent non-sedated 3 Tesla MRI with Cube Proton Density MRI sequence at the
same time as their initial clinical visit. Serial clinical examinations were
conducted at routine 4 week intervals and the functional performance scores were
recorded. MRI findings were divided into pre-ganglionic and post-ganglionic
injuries and a radiological scoring system (Shriners Radiological Score) was
developed for this study. RESULTS: Proton Density MRI was able to differentiate
between pre-ganglionic and post-ganglionic injuries. Radiological scores
(Shriners Radiological Score) correlated better with functional performance at 6
months of age (P = .022) than the initial clinical examinations (Active Movement
Scale P = .213 and Toronto P = .320). CONCLUSIONS: Rapid non-sedated volumetric
Cube Proton Density MRI protocol performed at initial clinical presentation can
accurately grade severity of brachial plexus birth palsy injury and predict
functional performance at 6 months of age.
PMID- 27606503
TI - Multiple Roles of Isocyanides in Palladium-Catalyzed Imidoylative Couplings: A
Mechanistic Study.
AB - Kinetic, spectroscopic and computational studies examining a palladium-catalyzed
imidoylative coupling highlight the dual role of isocyanides as both substrates
and ligands for this class of transformations. The synthesis of secondary amides
from aryl halides and water is presented as a case study. The kinetics of the
oxidative addition of ArI with RNC-ligated Pd0 species have been studied and the
resulting imidoyl complex [(ArC=NR)Pd(CNR)2 I] (Ar=4-F-C6 H4 , R=tBu) has been
isolated and characterized by X-ray diffraction. The unprecedented ability of
this RNC-ligated imidoyl-Pd complex to undergo reductive elimination at room
temperature to give the amide in the presence of water and an F- /HF buffer is
demonstrated. Its behavior in solution has also been characterized, revealing an
unexpected strong tendency to give cationic complexes, and notably
[(ArC=NR)Pd(CNR)3 ]+ with excess isocyanide and [(ArC=NR)Pd(PP^ )(CNR)]+ with
bidentate phosphines (PP^ ). These species may be responsible for catalyst
deactivation and side-reactions. Ab initio calculations performed at the DFT
level allowed us to rationalize the multiple roles of RNC in the different steps
of the catalytic cycle.
PMID- 27606545
TI - Limited association between scalp psoriasis and psoriatic arthritis severity and
treatment response.
AB - OBJECTIVES: We evaluated whether scalp psoriasis (PsO) is associated with
psoriatic arthritis (PsA) severity and/or with treatment response to etanercept.
METHODS: Patients with moderate-to-severe PsO and active PsA received etanercept
50 mg once weekly for 24 weeks. Patients were stratified according to whether
scalp PsO was present at baseline. Demographics and disease characteristics were
compared at baseline and after 12 and 24 weeks of treatment with etanercept.
RESULTS: Scalp PsO was present in 273/373 (73.2%) patients; they were
significantly younger and a higher proportion were male versus those without
scalp PsO. At baseline, the patient global assessment psoriasis score was
significantly higher for patients with scalp PsO versus without (67.0 vs. 57.9,
p<0.01); tender joint count was significantly higher for patients without scalp
PsO (6.0 vs. 5.0, p<0.05). A higher proportion of patients without versus with
scalp PsO achieved enthesitis <=1 at Week 12 (91.5% vs. 81.7%, p<0.05) and
dactylitis <=1 at week 24 (93.9% vs. 85.6%, p<0.05). Patients with scalp PsO
showed significantly greater improvements in fatigue and joint pain at weeks 12
and 24, and a greater proportion achieved a score <=0.5 in the health assessment
questionnaire at week 12 (65.2% vs. 53.0%, p<0.05). CONCLUSIONS: Scalp PsO was
not clearly associated with PsA severity, and it did not affect treatment
response. Patients without scalp PsO exhibited greater improvements in objective
joint outcomes, whereas patients with scalp PsO experienced better outcomes in
patient-reported outcomes.
PMID- 27606547
TI - Cloud-based MOTIFSIM: Detecting Similarity in Large DNA Motif Data Sets.
AB - We developed the cloud-based MOTIFSIM on Amazon Web Services (AWS) cloud. The
tool is an extended version from our web-based tool version 2.0, which was
developed based on a novel algorithm for detecting similarity in multiple DNA
motif data sets. This cloud-based version further allows researchers to exploit
the computing resources available from AWS to detect similarity in multiple large
scale DNA motif data sets resulting from the next-generation sequencing
technology. The tool is highly scalable with expandable AWS.
PMID- 27606546
TI - Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting
Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the
Treatment of Alzheimer's Disease.
AB - Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases
(HDAC) has recently been validated as a potentially novel therapeutic approach
for Alzheimer's disease (AD). To further extend this concept, we designed and
synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors,
and we validated this systems therapeutics approach. Following the implementation
of structure- and knowledge-based approaches, initial hits were designed and were
shown to validate our hypothesis of dual in vitro inhibition. Then, an
optimization strategy was pursued to obtain a proper tool compound for in vivo
testing in AD models. Initial hits were translated into molecules with adequate
cellular functional responses (histone acetylation and cAMP/cGMP response element
binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic
window (>1 log unit), and the ability to cross the blood-brain barrier, leading
to the identification of 7 as a candidate for in vivo proof-of-concept testing (
Cuadrado-Tejedor, M.; Garcia-Barroso, C.; Sanchez-Arias, J. A.; Rabal, O.;
Mederos, S.; Ugarte, A.; Franco, R.; Segura, V.; Perea, G.; Oyarzabal, J.; Garcia
Osta, A. Neuropsychopharmacology 2016 , in press, doi: 10.1038/npp.2016.163 ).
PMID- 27606548
TI - Survey of the Statewide Impact of Payer Source on Referral of Small Burns to Burn
Centers.
AB - It is generally agreed that patients with large burns will be referred to
organized burn centers, however, the referral of patients with smaller burns is
less certain. A two-part survey was conducted to identify referral patterns for
burn patients that meet American Burn Association referral criteria, and any
effect insurance type might have on the referral patterns. The emergency
departments of our state hospital association's member hospitals were contacted
seeking a referral for a fictitious patient with a third-degree scald of the
dominant hand. The referral sites were contacted twice, first stating that the
patient had commercial insurance, next stating that the patient had Medicaid.
Data collected included wait time for an appointment or reasons for denial of an
appointment. Of 218 hospitals, 46 were excluded because they did not offer
emergency care, and eight because they were listed as burn centers on the
American Burn Association website. Of the remaining 164, 119 (73%) would refer to
a burn center, 21 (13%) to a plastic surgeon, 10 (6%) to a hand surgeon, 7 (4%)
to a wound center, 7 (4%) to another nonburn physician resource. There was no
difference in wait time to the first available appointment with regards to
insurance type (6.56 +/- 4.68 vs 6.53 +/- 5.05 days). Our state's referral
pattern gives us insight into the regional referral pattern. This information
will be used to guide a focused education and communication program to provide
better service for the burn victims of our state.
PMID- 27606549
TI - Grip and Muscle Strength Dynamometry Are Reliable and Valid in Patients With
Unhealed Minor Burn Wounds.
AB - Small burns are common and can cause disproportionate levels of disability. The
ability to measure muscle impairment and consequent functional disability is a
necessity during rehabilitation of patients. This study aimed to determine the
reliability and validity of grip and muscle strength dynamometry in patients with
unhealed, minor burn wounds. Grip and muscle strength were assessed three times
on each side. Assessment occurred at presentation for the initial injury and
again every other day (or every 5 days beyond 10 days post injury) until
discharge from the service. Reliability was assessed using intraclass
correlation. Minimum detectable differences were calculated for each muscle
group. Validity was assessed using regression analysis, incorporating appropriate
burn severity measures and patient demographics. Thirty patients with TBSA <=15%
were assessed. Both grip and muscle strength demonstrated very good reliability
(intraclass correlation coefficient: 0.85-0.96). Minimum detectable differences
ranged from 3.8 to 8.0 kg. Validity of both forms of dynamometry was confirmed
through associations with gender for all muscle groups (P < .001). In addition,
grip strength was associated with the dominant hand (P = .002) and time to
assessment (P < .001). Strength was seen to improve over time in all muscle
groups. Grip and muscle strength dynamometry are reliable and valid assessments
of strength and are applicable for clinical use in patients who have unhealed,
minor burn wounds.
PMID- 27606550
TI - Extracorporeal Life Support Use in Adult Burn Patients.
AB - Burn-related cardiopulmonary failure causes significant morbidity and is
associated with increased risk of death. Extracorporeal life support (ECLS) may
be used to support burn patients, but its efficacy and safety in this population
have not been well defined. This study examined survival rates and risk factors
for death in adult burn patients who received ECLS. Retrospective data from the
Extracorporeal Life Support Organization international registry were analyzed to
determine clinical outcomes and risk factors for death in adult burn patients
treated with ECLS. During the study period, we identified 58 adult burn patients
who were treated with ECLS. Overall survival to hospital discharge was 43%.
Survivors and nonsurvivors were similar in age, gender, body weight, mode of ECLS
used, and duration of ECLS. Nonsurvivors had lower pH values (7.15 vs 7.30, P <
.001) and higher pCO2 values (65.5 vs 50.5, P = .038) before initiation of ECLS.
Nonsurvivors had higher rates of renal failure (49 vs 16%, P = .01) and renal
replacement therapy (70 vs 36%, P = .016). Infection was documented in 21
patients; survival in this group was 43%. Multivariate logistic regression
analysis identified acidosis (pH < 7.16) and the use of inotropic/vasopressor
medications before ECLS as risk factors associated with increased risk of
mortality. ECLS appears to be a viable treatment option for adult burn patients
with cardiopulmonary failure. ECLS survival in adult burn victims is similar to
that observed in nonburn patient populations treated with ECLS.
PMID- 27606551
TI - A Comment on a Meta-analysis That Suggests Efficacy of Albumin in Burn Shock
Resuscitation.
PMID- 27606552
TI - Scald Burn Injuries Caused by Showers Among the Adult Population in the Southwest
Region.
PMID- 27606553
TI - 2.5% Mafenide Acetate: A Cost-Effective Alternative to the 5% Solution for Burn
Wounds.
AB - Mafenide acetate is an antimicrobial agent used to decrease the bacterial load
for burn wounds. The 5% solution is more commonly used yet double the cost of its
2.5% counterpart. This study aims to evaluate outcomes and cost associated with
the use of 2.5 vs 5% mafenide acetate formulation in the adult burn population.
Adult patients (>=18 years) receiving 2.5% mafenide acetate during an 11-month
period between 2014 and 2015, corresponding to a policy change in favor of the
use of 2.5% mafenide acetate, were queried. Historical controls, patients
receiving 5% mafenide acetate, were also reviewed during an 11-month period
between 2013 and 2014. A retrospective review was performed comparing wound
infection rate, bacteremia, sepsis, pneumonia, duration of mafenide therapy,
length of hospital stay, mortality, and cost. A total of 54 and 65 patients
received 2.5 and 5% mafenide acetate, respectively. There was no difference in
wound infection, bacteremia, sepsis, pneumonia, duration of treatment, and
mortality between the two groups. No adverse events occurred in either group
directly related to mafenide. Candida and Staph species were the two most common
isolates in the 2.5% group, whereas Pseudomonas and Staph species were the most
common in the 5% arm. The mean cost of 2.5% mafenide therapy was $1494.92
compared with $3741.39 for 5% mafenide acetate. The 2.5% concentration
demonstrates to be an equally efficacious and cost-effective alternative to the
5% concentration. Burn centers should consider the use of the more dilute
preparation for burn wound infection prophylaxis as it may reduce the cost
without compromising patient safety.
PMID- 27606554
TI - Time Matters in Severe Frostbite: Assessment of Limb/Digit Salvage on the
Individual Patient Level.
AB - Severe frostbite is associated with high levels of morbidity through loss of
digits or limbs. The aim of this study was to examine the salvage rate following
severe frostbite injury. Frostbite patients from 2006 to 2014 were identified in
the prospectively maintained database at a single urban burn and trauma center.
Patients with imaging demonstrating a lack of blood flow in limbs/digits were
included in the analysis (N = 73). The Hennepin Frostbite Score was used to
quantify frostbite injury and salvage. This score provides a single value to
assess each individual patient's salvage rate. The majority of patients with
perfusion deficits were male (80%) with an average age of 42 years (range 11-83
years). Patients requiring amputation tended to be older (P = .002), have more
tissue impacted by frostbite (P < .001), and experienced a longer time from
rewarming to thrombolytic therapy (P = .001). A majority of patients (62%)
received thrombolytic treatment. The percentage of patients requiring amputation
was lower and the salvage rate was higher in patients treated with thrombolytics;
however, the differences failed to reach statistical significance (P = .092 and P
= .061, respectively). The rate of salvage decreases as the time from rewarming
to thrombolytic therapy increases. Regression analysis demonstrates an additional
26.8% salvage loss with each hour of delayed treatment (P = .006). When the
amount of tissue at risk for amputation is included in the model, each hour delay
in thrombolytic treatment results in a 28.1% decrease in salvage (P = .011). This
study demonstrates a significant decrease in limb/digit salvage with each hour of
delayed administration of thrombolytics in patients with severe frostbite.
PMID- 27606555
TI - Herpes Zoster Masquerading as a Chemical Burn Secondary to Hair Dye.
AB - Chemical burns secondary to hair dye are very rare but have been reported. Here,
we present a case of herpes zoster, which was initially mistaken for a chemical
burn. Herpes zoster reactivation (shingles) is common and can give rise to skin
loss clinically similar to that of a burn. It is important that clinicians
consider this alternative diagnosis to ensure that timely antiviral therapy is
initiated so as to reduce further skin loss and future scarring.
PMID- 27606556
TI - A Comparative Examination of the Clinical Outcome and Histological Appearance of
Cryopreserved and Fresh Split-Thickness Skin Grafts.
AB - The clinical use of frozen, human allogeneic skin grafts is considered a suitable
alternative to freshly harvested allogeneic skin grafts when the latter are not
available. However, limited functional and histological information exists
regarding the effects of cryopreservation on allogeneic skin grafts, especially
those across mismatched histocompatibility barriers. Thus, we performed a side-by
side comparative study of fresh vs frozen skin grafts, across both minor and
major histocompatibility barriers, in a miniature swine model. Since porcine skin
shares many physical and immunological properties with human skin, our findings
have relevance to current clinical practices involving allogeneic grafting and
may support future, temporary wound therapies involving frozen xenografts,
comprised genetically modified porcine skin. Four miniature swine underwent
harvest and grafting of split-thickness skin, with and without cryopreservation,
in order to observe autologous grafts and grafts across minor and major
histocompatibility barriers. A biopsy of the grafts was done at regular intervals
for study of architecture, vascularization, and outcomes. All grafts vascularized
without technical complications. Differences were noted in the early appearance
of some fresh vs frozen grafts, but no significant difference was observed in
overall survival times in any of the experimental groups. These results
demonstrate that despite early observable differences in the healing process,
cryopreservation and thawing does not significantly affect long-term graft
survival or time to rejection, thus supporting the clinical and experimental use
of fresh and frozen split-thickness skin grafts as comparable and
interchangeable.
PMID- 27606557
TI - Surgical Management of Levamisole-Adulterated Cocaine Induced Soft Tissue
Necrosis: Case Study and Treatment Algorithm.
AB - Levamisole is an increasingly common cocaine adulterant that can cause severe and
rapid onset cutaneous vasculitis in humans. While most cases may be managed
conservatively, we describe a series of patients in whom the extent of skin and
soft tissue necrosis mandated surgical intervention. A retrospective review of
all patients admitted to one of two regional burn centers between 2006 and 2016
for soft tissue necrosis after exposure to levamisole-adulterated cocaine was
included in our study. Ten patients, majority female (9/10) with an average age
of 43.4 years (range 31-57), were included. Cocaine usage before presentation
averaged 6 days (range 1-14). Presenting complaints consisted of arthralgia
(5/10), fever (7/10), and purpuric lesions (10/10). Average TBSA involvement was
23.5% (range 4-70). Immunological testing revealed perinuclear antineutrophil
cytoplasmic antibody (pANCA+) in 8 of 10 and cytoplasmic antineutrophil
cytoplasmic antibody (cANCA+) in 4 of 8 patients. Operative intervention occurred
by postadmission day 11.6 (range 3-30). The mean number of operations required
was 3 (range 2-6); length of stay averaged 46.8 days (range 14-120); and survival
to discharge was 100% (10/10). To our knowledge, this is the largest case study
detailing the surgical management of levamisole-associated skin necrosis.
Additionally, we describe the most extensive case of this disease process at 70%
TBSA involvement. Based on our experience, we recommend waiting for purpuric rash
resolution and soft tissue necrosis to be fully demarcated before fascial
debridement and then staged skin grafting with allograft followed by autograft.
PMID- 27606558
TI - Sedation and Analgesia for Dressing Change: A Survey of American Burn Association
Burn Centers.
AB - Pain and sedation management for patients undergoing burn dressing change can be
challenging. Variations appear to exist in the selection of medications before
and during burn dressing change. To determine if institutional variations exist
in pain and sedation management for burn dressing change, an online survey was
sent to ABA Burn Center nurses and physicians. Three hundred seventy-eight
anonymous responses were received from nurses (72%), nurse practitioners (10%),
and physicians (18%). Burn centers had adult (22%), pediatric (12%), or pediatric
and adult (66%) patients. Eighty percentage of centers had >200 patients/year.
Sixty-eight percentage always used a premedication. Oxycodone and morphine or
fentanyl was the most frequently used per oral (PO) and intravenous (IV) opioid
premedication, respectively. The most common IV premedication anxiolytic were
benzodiazepines. Sixty-eight percentage always used a long-acting opioid.
Anesthetic regimen was decided case-by-case (47%) or specific protocol (24%).
Protocol was followed always (18%) or mostly (55%). Patients' procedural pain
could be better controlled 20% of the time. Pain regimen was altered most of the
time (25%). Providers differed rarely (39%) and sometimes (44%) regarding
preferred regimen. Ketamine was the most common deep sedative. A dedicated
anesthesiologist was rarely (33%) consulted, determined case-by-case (33%) or
prior failure/excess pain (19%). Acute pain service was never (51%) or rarely
(35%) consulted. Pain and sedation management for burn dressing change is
difficult and variations in approach exist among burn centers. Such management
needs individualized care. Providers must be responsive to pain alterations.
Consultation with anesthesia providers may be needed in specific cases. Further
studies need to be completed to demonstrate the most effective means of
controlling burn pain and evaluating patient outcomes.
PMID- 27606559
TI - Cutaneous Functional Units Predict Shoulder Range of Motion Recovery in Children
Receiving Rehabilitation.
AB - Cutaneous functional units (CFUs) are fields of skin that functionally contribute
to range of motion (ROM) at an associated joint. When replaced with scar tissue,
the skin is less extensible and may result in loss of movement at the joint.
Consideration of the amount of CFU affected by burn injury is increasingly being
used to predict the development of burn scar contracture (BSC) in burn survivors.
Previous work established that, in adults, burn rehabilitation time per CFU was
the greatest predictor of preventing BSC. Our study aimed to examine the direct
relationship between percent involvement of CFU and ROM achieved in children with
BSC who received 6 months of rehabilitation therapy services. ROM was measured at
baseline and throughout the study period using traditional methods of goniometry
as well as three-dimensional motion capture during the performance of functional
tasks. Burn extent and distribution were mapped using an electronic diagram to
calculate the percentage of CFU affected by scarring or skin grafts. Pearson's
correlations and multivariate linear regression analyses were performed to
determine associations between variables. Results showed that percent CFU
involvement was negatively correlated with maximal goniometric and functional
shoulder ROM achieved. That is, the amount of a given CFU scarred was predictive
of less ROM achieved in the associated area. Percentage of CFU involved did not
significantly correlate with baseline shoulder ROM, suggesting that other factors
may be associated with initial limitations in ROM. Evaluation of the percentage
of CFU scarred is useful for predicting shoulder ROM recovery with rehabilitation
and may be used to help guide clinical decision making and allocation of time and
resource for therapy services.
PMID- 27606560
TI - Peer Support Needs Among Adults With Burns.
AB - Research and anecdotal evidence has shown that burn survivors benefit from peer
support participation, but also that relatively few attend such groups. This
study investigated Dutch adult burn survivors' views on the reasons that promote
or prevent participation in peer support activities. In this study, a distinction
was made between those with and without an overt need for peer support and
between those who do and those who do not already experience peer contact.
Questionnaires were sent online and/or per post to adult Dutch burn survivors.
Data were analyzed using descriptive analyses, t-tests and chi tests. The results
indicate that the main perceived benefits of participation are related to
receiving and giving support rather than to personal developmental reasons. The
main perceived barriers to participation are related to positive emotional
states. Overall, the perceived benefits and barriers do not differ substantially
between those who do and those who do not report a need for peer support or those
who have and have not participated in peer support. The results of the present
research may be indicative of an existing misconception among burn survivors that
peer support is meant for people in great need and distress. Promoting the
possibly unknown personal developmental function of peer contact, but also the
importance of its reciprocal benefits might help in having more patients profit
from peer support.
PMID- 27606561
TI - Construction of Skin Graft Seams in Burn Patients: A Prospective Randomized
Double-Blinded Study.
AB - Prominent scars and contractures may form along the seams between adjacent skin
grafts. Seams may be constructed either by approximating the graft edges (AP), or
by slightly overlapping the graft edges (OV), but it is not known if one
technique creates a less conspicuous seam scar. The purpose of this study was to
compare seam scars between seams constructed using the AP and OV techniques. This
was a prospective within-patient and within-seam controlled study in adult burn
patients treated at an American Burn Association-verified burn center. At skin
graft application and seam construction, study seams were divided in half. One
half of the seam was made by approximating the graft edges (AP group), while the
other half was made by overlapping graft edges (OV group), before identical
staple or suture fixation of each half. The AP or OV technique was randomly
assigned to the medial or lateral ends of transversely oriented seams or to the
proximal and distal ends of longitudinally oriented seams. At 3, 6, and 12 months
post surgery, a blinded rater compared the two halves of each study seam scar
using the Vancouver Scar Score (VSS). Subjects were also blinded and rated each
half of their study seam using a 0 (poor) to 10 (excellent) visual analogue
scale. Values are shown as the median (Q1-Q3). There were 44 study seams among 19
subjects (age 51 [36-70] years, with % TBSA burn 10 [7-18], % BSA full-thickness
burn 8 [6-15]). Study seams were constructed at 10 (4-15) days post burn. Study
seam length was 14.5 (10.3-18.0) cm, with 25% transversely oriented and 75%
longitudinally oriented, and with 35/44 seams (80%) between meshed grafts and
9/44 (20%) between sheet grafts. There were no significant differences in any of
the individual domain VSS scores (height, pliability, vascularity, and
pigmentation) or total VSS score between AP and OV seams at 3, 6, and 12 months.
At 12 months, among the 30 study seams that were visible to the subjects, the
visual analogue scale score for the AP seams was 9 (8.5-10), which did not differ
significantly from the OV seams (9.5 [8.45-10], P = .821). Overlapping or
approximating adjacent skin grafts at the time of seam construction does not
appear to affect final seam scar quality.
PMID- 27606562
TI - Factors Implicated in Safety-related Firefighter Fatalities.
AB - Firefighting is wrought with risk, as 80-100 firefighters (FFs) die on the job
each year in the United States. Many of the fatalities have been analyzed by the
National Institute for Occupational Safety and Health (NIOSH) to determine
contributing factors. The purpose of this study is to determine variables that
put FFs at risk for potentially preventable workplace mortality such as use of
personal protective equipment (PPE), seat belts, and appropriate
training/fitness/clearance for duty. The NIOSH FF Fatality Database reports from
2009 to 2014 were analyzed. Data including age, gender, years on the job,
weather, other calls on the same shift, and department type were compared between
FFs who employed PPE, seat belts, or wellness/fitness and those who did not. A
second group of FFs was determined by NIOSH to have inexperience, lack of
training, or inappropriate clearance for duty implicated in their fatalities.
Comparisons for the second group were between those whose department used
training and safety-related standard operating protocols and those who did not.
In 84/176 deaths, PPE/seat belts/fitness was implicated in the fatality. Lack of
PPE was more likely on clear days (P = .03) but less likely on cloudy and windy
days (P < .001). These FFs dying with lack of PPE had more time on the job in a
single department, 18 vs 13 years (P = .03), and more time in a volunteer
department, 17 vs 8 years (P < .01). Being deployed on another call during the
same shift was associated with lack of PPE-34 vs 16% of those who had not been on
another call (P = .005). Lack of training, experience, or medical clearance was
implicated in fatalities for 100/176 FFs. FFs who worked in departments that
lacked standard operating protocols for respirator fit testing, PPE, fitness
testing, rapid intervention, medical clearance, safety/distress alarms, vehicle
maintenance, or incident command were statistically more likely to have lack of
experience/training/clearance implicated in the fatality. Good weather during a
call and more years on the job, particularly in a volunteer department, are
associated with FF mortality related to unsafe practices. These factors might
create an air of complacency that puts FFs at risk for safety-related omissions.
Having been on a recent call may create distraction or fatigue that puts FF at
risk during subsequent calls. Lack of key safety-related protocols appears to put
FFs at risk of mortality, and the risk may be increasing over time. Further study
and prevention efforts from multidisciplinary groups are needed to better
understand and combat this problem.
PMID- 27606563
TI - The Nature of a Hard Protein Corona Forming on Quantum Dots Exposed to Human
Blood Serum.
AB - Biological responses of cells and organisms to nanoparticle exposure crucially
depend on the properties of the protein adsorption layer ("protein corona")
forming on nanoparticle surfaces and their characterization is a crucial step
toward a deep, mechanistic understanding of their build-up. Previously,
adsorption of one type of model protein on nanoparticles was systematically
studied in situ by using fluorescence correlation spectroscopy. Here, the first
such study of interactions is presented between water-solubilized CdSe/ZnS
quantum dots (QDs) and a complex biofluid, human blood serum. Despite the large
number of proteins in serum, a protein layer of well-defined (average) thickness
forming on QD surfaces is observed. Both the thickness and the apparent binding
affinity depend on the type of QD surface ligand. Kinetic experiments reveal that
the protein corona formed from serum is irreversibly bound, whereas the one
formed from human serum albumin was earlier observed to be reversible. By using
sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry,
the most abundant serum proteins contributing to the formation of a hard corona
on the QDs are identified.
PMID- 27606564
TI - Comparison of Healing Following Tooth Extraction With Ridge Preservation Using
Anorganic Bovine Bone Mineral Particulate and Self-Expanding Composite Graft.
AB - OBJECTIVES: To study the radiographic mean grey values after bone grafting and to
clinically evaluate the intraoral alveolar ridge dimensional stability with
anorganic bovine bone mineral (ABBM) particulate and a patented self-expanding
composite graft (SECG) after 6 months of healing. METHODS: A total of 20 single
rooted tooth-extraction sites grafted with either ABBM or SECG were evaluated
radiographically and clinically after 6 months of healing, prior to dental
implant placement. A multivariable mixed regression model was used. RESULTS: Mean
grey values at the coronal, midroot, and apex levels within the socket were
compared. A significant difference was shown in the midroot and apex maxillary
regions. For both of these regions, the estimated mean grey value of ABBM was
significantly lower than that of SECG. No significant difference was noted in the
ridge-width change patterns between the two materials. CONCLUSION: This study
supports that suggestion that newer SECG is as efficacious in terms of mean grey
value and alveolar ridge stability as the previously available ABBM.
PMID- 27606565
TI - Case Report of Posterior Crossbite: Description of an Effective Treatment
Protocol.
AB - Early treatment of functional unilateral posterior crossbite during the mixed
dentition stage is extremely important, as it provides the correct positioning of
osseous bases, teeth, and the temporomandibular joint when the stomatognathic
system is in growth and development. This article reports on a 9-year-old patient
who presented with functional unilateral posterior crossbite and was treated with
a modified Hyrax expander. The case report highlights a simple, low-cost,
effective treatment protocol. The malocclusion was corrected with 15 days of
active use of the appliance, 5 months of use for retention purposes, and 5 years
of post-treatment follow-up. The stability in the long-term treatment is highly
dependent on early diagnosis by the clinician and the elimination of the
etiological factor through use of the proper appliance.
PMID- 27606566
TI - Subjective Assessment of Enamelon(r) Preventive Treatment Gel in a Self-Reported
Dry-Mouth Population.
AB - BACKGROUND: The efficacy of stannous fluoride toothpastes is well established for
reducing caries, plaque, and gingivitis and relieving the discomfort of dentin
hypersensitivity. Management of dry mouth may include relief remedies in addition
to usual oral hygiene methods to maintain oral health and improve quality of
life. This 6-week, single-blind, randomized, two-period crossover clinical study
was designed to evaluate the oral tolerance and potential of Enamelon(r)
Preventive Treatment Gel (EPTG), with 0.4% stannous fluoride, to relieve subject
perceived dry-mouth symptoms in a self-reported dry-mouth population, after 14
days of use, compared to a marketed over-the-counter (OTC) artificial saliva gel
product (Biotene(r) Oral Balance Gel [BOBG]). METHODS: Following a 7-day washout
period, 52 qualified subjects with self-reported dry-mouth symptoms received EPTG
or BOBG for once-daily use for 14 days. All subjects brushed each morning and
evening with a standard fluoride toothpaste (Sensodyne(r) ProNamel). Each evening
and following brushing with the Sensodyne ProNamel, subjects used their assigned
gel product (EPTG or BOBG) as directed. On Days 1, 8, and 15, subjects received
an oral examination and assessed relief of dry-mouth symptoms using a product
performance questionnaire (PPQ). Procedures were repeated with the alternate
product for another 14-day period, following a 7-day washout. Data for each
efficacy endpoint were analyzed using crossover ANOVA model. RESULTS: No
treatment-related adverse events were reported in this study, and both products
were well tolerated by the subjects. Compared to pre-study ratings of usual dry
mouth remedies, both BOBG and EPTG significantly reduced dry-mouth symptoms
following 14 days of use. BOBG was statistically significantly better than EPTG
in relieving many of the principal dry-mouth symptoms such as providing immediate
relief, having an immediate moisturizing and immediate lubricating effect,
feeling comfortable in the mouth, soothing the mouth, effectively lubricating the
mouth, and protecting the mouth from drying out (P < .05). Compared with
subjects' ratings of their usual dry-mouth remedies, EPTG also provided relief of
several dry-mouth symptoms at both Days 8 and 15 (P < .05). CONCLUSION: Based on
subjective measures of dry mouth and compared with pre-study ratings of usual
remedies, subjects perceived that EPTG helped to manage symptoms such as
relieving the discomfort of dry mouth, immediately moisturizing and lubricating,
effectively lubricating, protecting from drying out, and providing long-lasting
moisturization and long-lasting lubrication, and was not irritating to dry-mouth
tissues. BOBG, the positive control, was significantly better than EPTG in
relieving dry-mouth symptoms over a 2-week period and was not irritating.
PRACTICAL IMPLICATIONS: Patients with dry-mouth symptoms may benefit from daily
use of a non-irritating, OTC fluoride preventive treatment gel product to relieve
symptoms while also reducing the risks of developing dental caries,
demineralization, dentin hypersensitivity, and gingivitis.
PMID- 27606567
TI - Use of Double Layer of Acellular Dermal Matrix and Modified Tunnel Technique to
Treat Multiple Adjacent Gingival Recession Defects.
AB - The goal of connective tissue grafting is to cover exposed root surfaces with
gingival tissues that are stable and have a natural appearance. The use of an
acellular dermal matrix (ADM) has been shown to be a successful alternative to
the palatal connective tissue graft. Use of a double layer of an ADM has been
shown to have stable results for 1 year. Tunnel grafting techniques can yield
root coverage with a natural appearing soft-tissue architecture. The purpose of
this case report is to demonstrate the use of a modified tunnel technique and a
double layer of ADM in the treatment of multiple adjacent gingival recession
defects. Treated teeth were found to have root coverage and natural soft-tissue
contours that were stable at 20 months.
PMID- 27606568
TI - The effect of bacteriospermia and leukocytospermia on conventional and
nonconventional semen parameters in healthy young normozoospermic males.
AB - Bacterial semen inflammation/infection is an important diagnostic and therapeutic
problem in contemporary andrology. The molecular mechanism by which inflammatory
mediators compromise the fertilizing potential of germ cells is complex and
multifactorial, and it remains unclear. To improve the understanding of the
pathophysiology of human subfertility/infertility caused or complicated by
reproductive tract inflammation/infection, we simultaneously evaluated a set of
conventional (standard semen analysis) and nonconventional sperm parameters,
including subcellular changes in sperm membranes (phospholipid scrambling,
peroxidative damage, and phosphatidylserine (PS) externalization), mitochondria
(mitochondrial transmembrane potential, DeltaYm, and oxidoreductive capability),
and DNA fragmentation in healthy young normozoospermic males with asymptomatic
bacteriospermia and leukocytospermia. Both bacteriospermia and leukocytospermia
had a deleterious effect on standard sperm parameters, including sperm
concentration, motility and morphology. Bacteriospermia was associated with a
simultaneous decrease in mitochondrial transmembrane potential and an increase in
PS externalization, and with DNA fragmentation in both live and dead sperm. The
highest MDA concentrations in sperm lysates were observed in the presence of
leukocytes. This study demonstrates for the first time that bacteriospermia and
leukocytospermia compromise sperm quality in healthy young normozoospermic males.
Bacteria mainly participate in intrinsic mitochondria-dependent apoptotic cell
death mechanisms. Oxidative stress plays a relevant role in decreasing routine
sperm parameters during leukocytospermia. The value of these observations may be
significant and may support the development of a new diagnostic platform
(biomarkers) for infertile males with infections in the reproductive tract.
PMID- 27606569
TI - Immune mediators associated to male infertility in a mouse model of DNA
immunization with the sperm protease proacrosin.
AB - The immune response has relevant physiological functions both in the male and
female reproductive system, and must be tightly controlled to achieve a
successful pregnancy. Several immune factors have been related to infertility,
among them humoral and cellular immune responses triggered by sperm antigens. The
present study was aimed at evaluating the immune profile induced by DNA
immunization against the sperm protease proacrosin in CF1 male mice and its
effect upon fertility. Immunized animals exhibited higher anti-proacrosin
antibodies levels than controls (indirect ELISA), both in serum (p<0.01) and in
seminal vesicle fluid (SVF; p<0.05). IgG2a levels were higher than IgG1 in serum
(p<0.01) and similar in SVF. IL-10 and TGF-beta1 mRNA levels were lower in testis
(p<0.05), whereas TNF-alpha and IFN-gamma transcript levels were increased in SV
tissue (p<0.05). Immunized mice showed a trend toward higher IFN-gamma
concentration in serum and SVF than controls. Male fertility rate was diminished
in immunized mice (p<0.01) and inversely correlated with serum and SVF anti
proacrosin IgG levels (p<0.001). Immunized animals also had fewer pups born than
controls (p<0.01). To our knowledge, this is the first report on DNA immunization
done in CF1 mice. Injection of proacrosin DNA induces an immune response in the
male reproductive tract characterized by high levels of specific antibodies and
cytokine changes. These factors may alter the crucial balance of the genital
tract microenvironment required for adequate fertilization and pregnancy.
PMID- 27606570
TI - Developmental validation of the DNAscanTM Rapid DNA AnalysisTM instrument and
expert system for reference sample processing.
AB - Since the implementation of forensic DNA typing in labs more than 20 years ago,
the analysis procedures and data interpretation have always been conducted in a
laboratory by highly trained and qualified scientific personnel. Rapid DNA
technology has the potential to expand testing capabilities within forensic
laboratories and to allow forensic STR analysis to be performed outside the
physical boundaries of the traditional laboratory. The developmental validation
of the DNAscan/ANDE Rapid DNA Analysis System was completed using a BioChipSetTM
Cassette consumable designed for high DNA content samples, such as single source
buccal swabs. A total of eight laboratories participated in the testing which
totaled over 2300 swabs, and included nearly 1400 unique individuals. The goal of
this extensive study was to obtain, document, analyze, and assess DNAscan and its
internal Expert System to reliably genotype reference samples in a manner
compliant with the FBI's Quality Assurance Standards (QAS) and the NDIS
Operational Procedures. The DNAscan System provided high quality, concordant
results for reference buccal swabs, including automated data analysis with an
integrated Expert System. Seven external laboratories and NetBio, the developer
of the technology, participated in the validation testing demonstrating the
reproducibility and reliability of the system and its successful use in a variety
of settings by numerous operators. The DNAscan System demonstrated limited cross
reactivity with other species, was resilient in the presence of numerous
inhibitors, and provided reproducible results for both buccal and purified DNA
samples with sensitivity at a level appropriate for buccal swabs. The precision
and resolution of the system met industry standards for detection of micro
variants and displayed single base resolution. PCR-based studies provided
confidence that the system was robust and that the amplification reaction had
been optimized to provide high quality results. The DNAscan integrated Expert
System was examined as part of the Developmental Validation and successfully
interpreted the over 2000 samples tested with over 99.998% concordant alleles.
The system appropriately flagged samples for human review and failed both mixed
samples and samples with insufficient genetic information. These results
demonstrated the integrated Expert System makes correct allele calls without
human intervention.
PMID- 27606572
TI - All too common: bleeding and genetic variation.
PMID- 27606571
TI - Evading pre-existing anti-hinge antibody binding by hinge engineering.
AB - Antigen-binding fragments (Fab) and F(ab')2 antibodies serve as alternative
formats to full-length anti-bodies in therapeutic and immune assays. They provide
the advantage of small size, short serum half-life, and lack of effector
function. Several proteases associated with invasive diseases are known to cleave
antibodies in the hinge-region, and this results in anti-hinge antibodies (AHA)
toward the neoepitopes. The AHA can act as surrogate Fc and reintroduce the
properties of the Fc that are otherwise lacking in antibody fragments. While this
response is desired during the natural process of fighting disease, it is
commonly unwanted for therapeutic antibody fragments. In our study, we identify a
truncation in the lower hinge region of the antibody that maintains efficient
proteolytic cleavage by IdeS protease. The resulting neoepitope at the F(ab')2 C
terminus does not have detectable binding of pre-existing AHA, providing a
practical route to produce F(ab')2 in vitro by proteolytic digestion when the
binding of pre-existing AHA is undesired. We extend our studies to the upper
hinge region of the antibody and provide a detailed analysis of the contribution
of C-terminal residues of the upper hinge of human IgG1, IgG2 and IgG4 to pre
existing AHA reactivity in human serum. While no pre-existing antibodies are
observed toward the Fab of IgG2 and IgG4 isotype, a significant response is
observed toward most residues of the upper hinge of human IgG1. We identify a
T225L variant and the natural C-terminal D221 as solutions with minimal serum
reactivity. Our work now enables the production of Fab and F(ab')2 for
therapeutic and diagnostic immune assays that have minimal reactivity toward pre
existing AHA.
PMID- 27606574
TI - Probing the intrinsic optical Bloch-mode emission from a 3D photonic crystal.
AB - We report experimental observation of intrinsic Bloch-mode emission from a 3D
tungsten photonic crystal at low thermal excitation. After the successful removal
of conventional metallic emission (normal emission), it is possible to make an
accurate comparison of the Bloch-mode and the normal emission. For all biases, we
found that the emission intensity of the Bloch-mode is higher than that of the
normal emission. The Bloch-mode emission also exhibits a slower dependence on
[Formula: see text] than that of the normal emission. The observed higher
emission intensity and a different T-dependence is attributed to Bloch-mode
assisted emission where emitters have been located into a medium having local
density of states different than the isotropic case. Furthermore, our finite
difference time-domain (FDTD) simulation shows the presence of localized spots at
metal-air boundaries and corners, having intense electric field. The enhanced
plasmonic field and local non-equilibrium could induce a strong thermally
stimulated emission and may be the cause of our unusual observation.
PMID- 27606573
TI - A combination of different diagnostic tools allows identification of inactive
hepatitis B virus carriers at a single time point evaluation.
AB - BACKGROUND & AIMS: Serial evaluation of hepatitis B virus (HBV) DNA and
aminotransferase values is required for identification of inactive HBV carriers
(ICs). Recently, HBV surface antigen quantification (qHBsAg) and liver stiffness
measurement (LSM) have been proposed as diagnostic tools in chronic HBV
infection. The aim of this study was to evaluate the efficacy of HBV DNA
quantification, qHBsAg and LSM in diagnosing ICs at a single time point. METHODS:
Fifty-seven previously characterized ICs and 90 untreated HBsAg-/anti-HBe
positive patients [49 chronic hepatitis (CH), 41 cirrhosis] were enrolled. HBV
DNA <=2000 IU/mL, LSM <=6.2 kPa and qHBsAg <=1000 IU/mL were used as cut-offs to
evaluate sensitivity, specificity, positive predictive value (PPV), negative
predictive value (NPV) and diagnostic accuracy (DA). RESULTS: Combined HBV DNA
quantification and qHBsAg correctly identified 30/57 (52.6%) ICs showing 94%
sensitivity, 96% specificity, 98% PPV, 87% NPV and 95% DA. HBV DNA coupled with
LSM identified 40/57 (70.2%) ICs showing 97% sensitivity, 97% specificity, 98%
PPV, 95% NPV and 97% DA. Combined LSM and qHBsAg identified 33/57 (57.9%) ICs
showing 95% sensitivity, 78% specificity, 89% PPV, 89% NPV and 89% DA. The
evaluation of the three parameters altogether allowed the identification of 23/57
(40.3%) ICs showing 100% specificity, 96% sensitivity, 100% PPV, 92% NPV and 97%
DA. Similar results were obtained when either CH or cirrhotic patients were
excluded from the analysis. CONCLUSIONS: Combined evaluation of HBV DNA amount
with LSM and/or qHBsAg is a highly reliable tool allowing the identification of a
considerable number of HBV ICs at a single time point evaluation.
PMID- 27606576
TI - Is Google Translate Adequate for Facilitating Instrument Translation From English
to Mandarin?
PMID- 27606575
TI - Cognitive functions in children and adolescents with early-onset diabetes
mellitus in Egypt.
AB - : The objective of this study was to investigate performance on memory,
intelligence, and executive functions in children and adolescents with type 1
diabetes mellitus (T1DM) and to investigate the role of glycemic control,
hypoglycemic attacks and diabetic ketoacidosis. We compared 50 subjects with T1DM
with 30 healthy controls (ages between 7 and 16 years) using Benton Visual
Retention Test (BVRT), the Arabic version of the Wechsler Intelligence Scale for
Children (WISC), and Wisconsin Card Sorting Test (WCST). We also compared good
versus poor glycemic control in T1DM subjects. RESULTS: T1DM subjects had
significantly poorer performance than controls on all subtests of the BVRT, on
all subscales of the WISC (verbal, performance and total IQ) and on most subtests
of WCST (p < 0.05). T1DM subjects with good glycemic control performed
significantly better than subjects with poor glycemic control on all subtests of
the BVRT and on all subscales of the WISC (p < 0.05), but there was no difference
on the WCST. T1DM subjects differed from controls on memory, intelligence, and
executive functions. They also differed according to good or poor glycemic
control (except on the WCST). Cognitive performance significantly correlated with
a number of demographic and clinical variables.
PMID- 27606577
TI - 2016 Nursing Knowledge Big Data Science Initiative.
PMID- 27606578
TI - A Formative Program Evaluation of Electronic Clinical Tracking System
Documentation to Meet National Core Competencies.
PMID- 27606579
TI - Plastic Surgical Nursing Journal Information for Authors.
PMID- 27606580
TI - Letter to the Editor.
PMID- 27606581
TI - Response to the Letter to the Editor.
PMID- 27606582
TI - Taking Charge of Your Professional Growth and Development: Where Do I Start?
PMID- 27606583
TI - Letter From the President of PSNCB.
PMID- 27606584
TI - Understanding the Anatomy of the Upper Face When Providing Aesthetic Injection
Treatments.
AB - Advanced rejuvenation procedures for the upper face are becoming increasingly
popular for aesthetic providers but are considered a high-risk treatment area for
dermal filler/contouring products. Risks may range from bruising, which is
manageable, to blindness, most often irreversible. Detailed comprehension of the
facial anatomy is imperative when performing aesthetic injections including
neuromodulators and dermal filler/contouring products. Understanding the location
and function of the muscles, as well as landmarking the blood vessels and nerves,
will assist the aesthetic provider to perform safe, confident injection
procedures. This article focuses on the upper face anatomy as identified by the
author's cadaveric dissections and includes the treatment areas of the frontalis,
temporalis, and glabellar complex. The author's next article for the Plastic
Surgical Nursing journal will focus on the periorbital area.
PMID- 27606585
TI - The Value of Full Correction: Achieving Excellent and Affordable Results.
AB - Patients often come to medical aesthetic offices with hopes to fully correct lost
facial volume and achieve a natural appearance. Unfortunately, the cost per
syringe of dermal filler can be a barrier to desired outcomes. Many aesthetic
practitioners do the best they can with the amount of product the patient can
afford, often falling short of the "wow" effect for the patient. This article
describes what one office implemented to solve the conundrum of affordability
while still allowing offices to cover its own financial realities. This tool can
help patients achieve beautiful, natural, and affordable outcomes while helping
offices advance in manufacturer's tiers, improve word-of-mouth advertising, and
increase job satisfaction.
PMID- 27606586
TI - Pediatric Hand Injuries.
AB - Pediatric hand injuries are extremely common. Although many hand injuries are
adequately managed in the emergency department, some may need evaluation and
treatment by a pediatric hand surgeon to ensure a good functional outcome. This
article discusses the diagnosis and management of the most common pediatric hand
maladies: fingertip injuries/amputation, tendon injuries, and phalangeal and
metacarpal fractures. The plastic surgery nurse should be familiar with hand
injuries that require intervention to facilitate efficient management and optimal
postoperative care.
PMID- 27606587
TI - Medicinal Leech Therapy: Friend or Foe.
AB - Leech therapy is the ancient practice of bloodletting or bloodsucking and is
considered one of the oldest medical practices known. Its use has spanned
centuries and is still used in plastic surgery practices today when performing
free flaps and replants. The purpose of this article is to discuss the history of
this ancient therapy and to describe the leech and its present indications,
complications, contraindications, and techniques.
PMID- 27606588
TI - Herbal Supplements: Widely Used, Poorly Understood.
PMID- 27606589
TI - The Use of Autologous Fat Grafting for Treatment of Scar Tissue and Scar-Related
Conditions: A Systematic Review.
PMID- 27606590
TI - Understanding the Anatomy of the Upper Face When Providing Aesthetic Injection
Treatments.
PMID- 27606591
TI - Acid Activation in Phenyliodine Dicarboxylates: Direct Observation, Structures,
and Implications.
AB - The use of the hypervalent iodine reagents in oxidative processes has become a
staple in modern organic synthesis. Frequently, the reactivity of lambda3 iodanes
is further enhanced by acids (Lewis or Bronsted). The origin of such activation,
however, has remained elusive. Here, we use the common combination of PhI(OAc)2
with BF3.Et2O as a model to fully explore this activation phenomenon. In addition
to the spectroscopic assessment of the dynamic acid-base interaction, for the
first time the putative PIDA.BF3 complex has been isolated and its structure
determined by X-ray diffraction. Consequences of such activation are discussed
from a structural and electronic (DFT) points of views, including the origins of
the enhanced reactivity.
PMID- 27606592
TI - A Heat Vulnerability Index: Spatial Patterns of Exposure, Sensitivity and
Adaptive Capacity for Santiago de Chile.
AB - Climate change will worsen the high levels of urban vulnerability in Latin
American cities due to specific environmental stressors. Some impacts of climate
change, such as high temperatures in urban environments, have not yet been
addressed through adaptation strategies, which are based on poorly supported
data. These impacts remain outside the scope of urban planning. New spatially
explicit approaches that identify highly vulnerable urban areas and include
specific adaptation requirements are needed in current urban planning practices
to cope with heat hazards. In this paper, a heat vulnerability index is proposed
for Santiago, Chile. The index was created using a GIS-based spatial information
system and was constructed from spatially explicit indexes for exposure,
sensitivity and adaptive capacity levels derived from remote sensing data and
socio-economic information assessed via principal component analysis (PCA). The
objective of this study is to determine the levels of heat vulnerability at local
scales by providing insights into these indexes at the intra city scale. The
results reveal a spatial pattern of heat vulnerability with strong variations
among individual spatial indexes. While exposure and adaptive capacities depict a
clear spatial pattern, sensitivity follows a complex spatial distribution. These
conditions change when examining PCA results, showing that sensitivity is more
robust than exposure and adaptive capacity. These indexes can be used both for
urban planning purposes and for proposing specific policies and measures that can
help minimize heat hazards in highly dynamic urban areas. The proposed
methodology can be applied to other Latin American cities to support policy
making.
PMID- 27606593
TI - Proteomic Identification of Immunodiagnostic Antigens for Trypanosoma vivax
Infections in Cattle and Generation of a Proof-of-Concept Lateral Flow Test
Diagnostic Device.
AB - Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis
in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by
the bite of the tsetse fly vector. The parasite can also be mechanically
transmitted, and this has allowed its spread to South America. Diagnostics are
limited for this parasite and in farm settings diagnosis is mainly symptom-based.
We set out to identify, using a proteomic approach, candidate diagnostic antigens
to develop into an easy to use pen-side lateral flow test device. Two related
members the invariant surface glycoprotein family, TvY486_0045500 and
TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal
signal peptides and C-terminal transmembrane domains, were expressed in E. coli.
Both were developed into ELISA tests and one of them, TvY486_0045500, was
developed into a lateral flow test prototype. The tests were all evaluated blind
with 113 randomised serum samples, taken from 37 calves before and after
infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690
ELISA tests gave identical sensitivity and specificity values for T. vivax
infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%),
respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity
and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to
96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows
promise for the development of a pen-side lateral flow test for the diagnosis of
T. vivax animal African trypanosomosis.
PMID- 27606594
TI - Mapping QTL Contributing to Variation in Posterior Lobe Morphology between
Strains of Drosophila melanogaster.
AB - Closely-related, and otherwise morphologically similar insect species frequently
show striking divergence in the shape and/or size of male genital structures, a
phenomenon thought to be driven by sexual selection. Comparative interspecific
studies can help elucidate the evolutionary forces acting on genital structures
to drive this rapid differentiation. However, genetic dissection of sexual trait
divergence between species is frequently hampered by the difficulty generating
interspecific recombinants. Intraspecific variation can be leveraged to
investigate the genetics of rapidly-evolving sexual traits, and here we carry out
a genetic analysis of variation in the posterior lobe within D. melanogaster. The
lobe is a male-specific process emerging from the genital arch of D. melanogaster
and three closely-related species, is essential for copulation, and shows radical
divergence in form across species. There is also abundant variation within
species in the shape and size of the lobe, and while this variation is
considerably more subtle than that seen among species, it nonetheless provides
the raw material for QTL mapping. We created an advanced intercross population
from a pair of phenotypically-different inbred strains, and after phenotyping and
genotyping-by-sequencing the recombinants, mapped several QTL contributing to
various measures of lobe morphology. The additional generations of crossing over
in our mapping population led to QTL intervals that are smaller than is typical
for an F2 mapping design. The intervals we map overlap with a pair of lobe QTL we
previously identified in an independent mapping cross, potentially suggesting a
level of shared genetic control of trait variation. Our QTL additionally
implicate a suite of genes that have been shown to contribute to the development
of the posterior lobe. These loci are strong candidates to harbor naturally
segregating sites contributing to phenotypic variation within D. melanogaster,
and may also be those contributing to divergence in lobe morphology between
species.
PMID- 27606595
TI - Yersinia pestis Caf1 Protein: Effect of Sequence Polymorphism on Intrinsic
Disorder Propensity, Serological Cross-Reactivity and Cross-Protectivity of
Isoforms.
AB - Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic
activity and is a key protective antigen. It is generally conserved between
globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar
caucasica strains circulating within populations of common voles in Georgia and
Armenia were reported to carry a single substitution of alanine to serine. We
investigated polymorphism of the Caf1 sequences among other Y. pestis subsp.
microtus strains, which have a limited virulence in guinea pigs and in humans.
Sequencing of caf1 genes from 119 Y. pestis strains belonging to different
biovars within subsp. microtus showed that the Caf1 proteins exist in three
isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117)
found in Transcaucasian-highland and Pre-Araks natural plague foci #4-7, and a
novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague
focus #39. Both minor types are the progenies of the global isoform. In this
report, Caf1 polymorphism was analyzed by comparing predicted intrinsic disorder
propensities and potential protein-protein interactivities of the three Caf1
isoforms. The analysis revealed that these properties of Caf1 protein are
minimally affected by its polymorphism. All protein isoforms could be equally
detected by an immunochromatography test for plague at the lowest protein
concentration tested (1.0 ng/mL), which is the detection limit. When compared to
the classic Caf1NT1 isoform, the endemic Caf1NT2 or Caf1NT3 had lower
immunoreactivity in ELISA and lower indices of self- and cross-protection.
Despite a visible reduction in cross-protection between all Caf1 isoforms, our
data suggest that polymorphism in the caf1 gene may not allow the carriers of
Caf1NT2 or Caf1NT3 variants escaping from the Caf1NT1-mediated immunity to plague
in the case of a low-dose flea-borne infection.
PMID- 27606596
TI - Study on small airway function in asthmatics with fractional exhaled nitric oxide
and impulse oscillometry.
AB - OBJECTIVES: The invasive techniques can be direct and objective to assess small
airway function, but they have significant risks and inconveniences for patients
and cannot be repeated often. Some sophisticated techniques such as fractional
exhaled nitric oxide (FeNO) and impulse oscillometry (IOS) may surmount such
restrictions. Therefore, we investigated the relation among FeNO, IOS, and small
airway function in asthmatic patients. METHODS: We recruited 140 asthmatic
patients including 69 patients with small airway normal function and 71 patients
with small airway dysfunction. FeNO, eosinophil(EOS)count and total
immunoglobulin E (IgE) in peripheral blood, pulmonary function, as well as IOS
were measured. RESULTS: The levels of FeNO, the reactance area (AX), the resonant
frequency Fres and EOS were significantly increased in small airway dysfunction
group compared with small airway normal function group (P < 0.01 respectively). A
multiple regression model showed that FeNO, AX and Fres were correlative factors
of mid forced expiratory flow of percentages of predicted values [FEF25-75
(%pred)] (P < 0.01, respectively). A receiver operating characteristic (ROC)
analysis showed that the combination of FeNO, AX and Fres had a greater area
under the ROC curve (AUC) than each of them (AUC: 0.881, P < .001, 95%CI: 0.815
0.929). CONCLUSION: FeNO and IOS are helpful in diagnosis of small airway
dysfunction with high sensitivity and specificity, and FeNO combined with IOS can
better evaluate the small airway function in asthmatic patients.
PMID- 27606597
TI - Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using
Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal
Stem Cells.
AB - BACKGROUND: Tendon-bone healing following rotator cuff repairs is mainly impaired
by poor tissue quality. Demineralised bone matrix promotes healing of the tendon
bone interface but its role in the treatment of tendon tears with retraction has
not been investigated. We hypothesized that cortical demineralised bone matrix
used with minimally manipulated mesenchymal stem cells will result in improved
function and restoration of the tendon-bone interface with no difference between
xenogenic and allogenic scaffolds. MATERIALS AND METHODS: In an ovine model, the
patellar tendon was detached from the tibial tuberosity and a complete distal
tendon transverse defect measuring 1 cm was created. Suture anchors were used to
reattach the tendon and xenogenic demineralised bone matrix + minimally
manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone
matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge
the defect. Graft incorporation into the tendon and its effect on regeneration of
the enthesis was assessed using histomorphometry. Force plate analysis was used
to assess functional recovery. RESULTS: Compared to the xenograft, the allograft
was associated with significantly higher functional weight bearing at 6 (P =
0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was
accompanied by greater remodeling of the demineralised bone matrix into tendon
like tissue in the region of the defect (p = 0.015), and a more direct type of
enthesis characterized by significantly more fibrocartilage (p = 0.039). No
failures of tendon-bone healing were noted in either group. CONCLUSION:
Demineralised bone matrix used with minimally manipulated mesenchymal stem cells
promotes healing of the tendon-bone interface in an ovine model of acute tendon
retraction, with superior mechanical and histological results associated with use
of an allograft.
PMID- 27606598
TI - Temperature Regimes Impact Coral Assemblages along Environmental Gradients on
Lagoonal Reefs in Belize.
AB - Coral reefs are increasingly threatened by global and local anthropogenic
stressors such as rising seawater temperature, nutrient enrichment,
sedimentation, and overfishing. Although many studies have investigated the
impacts of local and global stressors on coral reefs, we still do not fully
understand how these stressors influence coral community structure, particularly
across environmental gradients on a reef system. Here, we investigate coral
community composition across three different temperature and productivity regimes
along a nearshore-offshore gradient on lagoonal reefs of the Belize Mesoamerican
Barrier Reef System (MBRS). A novel metric was developed using ultra-high
resolution satellite-derived estimates of sea surface temperatures (SST) to
classify reefs as exposed to low (lowTP), moderate (modTP), or high (highTP)
temperature parameters over 10 years (2003 to 2012). Coral species richness,
abundance, diversity, density, and percent cover were lower at highTP sites
relative to lowTP and modTP sites, but these coral community traits did not
differ significantly between lowTP and modTP sites. Analysis of coral life
history strategies revealed that highTP sites were dominated by hardy stress
tolerant and fast-growing weedy coral species, while lowTP and modTP sites
consisted of competitive, generalist, weedy, and stress-tolerant coral species.
Satellite-derived estimates of Chlorophyll-a (chl-a) were obtained for 13-years
(2003-2015) as a proxy for primary production. Chl-a concentrations were highest
at highTP sites, medial at modTP sites, and lowest at lowTP sites. Notably,
thermal parameters correlated better with coral community traits between site
types than productivity, suggesting that temperature (specifically number of days
above the thermal bleaching threshold) played a greater role in defining coral
community structure than productivity on the MBRS. Dominance of weedy and stress
tolerant genera at highTP sites suggests that corals utilizing these two life
history strategies may be better suited to cope with warmer oceans and thus may
warrant protective status under climate change.
PMID- 27606600
TI - Translational Science for Energy and Beyond.
AB - A clear challenge for the coming decades is decreasing the carbon intensity of
the global energy supply while simultaneously accommodating a rapid worldwide
increase in power demand. Meeting this challenge of providing abundant, clean
energy undoubtedly requires synergistic efforts between basic and applied
researchers in the chemical sciences to develop and deploy new technologies.
Among the available options, solar energy is one of the promising targets because
of the high abundance of solar photons over much of the globe. Similarly,
decarbonization of the global energy supply will require clean sources of
hydrogen to use as reducing equivalents for fuel and chemical feedstocks. In this
report, we discuss the importance of translational research-defined as work that
explicitly targets basic discovery as well as technology development-in the
context of photovoltaics and solar fuels. We focus on three representative
research programs encompassing translational research in government, industry,
and academia. We then discuss more broadly the benefits and challenges of
translational research models and offer recommendations for research programs
that address societal challenges in the energy sector and beyond.
PMID- 27606599
TI - An Alternative Strategy for Pan-acetyl-lysine Antibody Generation.
AB - Lysine acetylation is an important post-translational modification in cell
signaling. In acetylome studies, a high-quality pan-acetyl-lysine antibody is key
to successful enrichment of acetylated peptides for subsequent mass spectrometry
analysis. Here we show an alternative method to generate polyclonal pan-acetyl
lysine antibodies using a synthesized random library of acetylated peptides as
the antigen. Our antibodies are tested to be specific for acetyl-lysine
peptides/proteins via ELISA and dot blot. When pooled, five of our antibodies
show broad reactivity to acetyl-lysine peptides, complementing a commercial
antibody in terms of peptide coverage. The consensus sequence of peptides bound
by our antibody cocktail differs slightly from that of the commercial antibody.
Lastly, our antibodies are tested in a proof-of-concept to analyze the acetylome
of HEK293 cells. In total we identified 1557 acetylated peptides from 416
proteins. We thus demonstrated that our antibodies are well-qualified for
acetylome studies and can complement existing commercial antibodies.
PMID- 27606601
TI - Spatial genetic structure of the cyprinid fish Onychostoma lepturum on Hainan
Island.
AB - Population genetic structure of Onychostoma lepturum on Hainan Island was
investigated based on mitochondrial CR + cyt b region in 63 specimens collected
from four populations. Population analyses indicated significant genetic
structure (FST = 0.749) and displayed a significant relationship between
phylogeny and geography (NST = 0.750 and GST = 0.140). Thirty-one mtDNA
haplotypes were classified into four lineages, and these lineages had an almost
allopatric distribution. The results of a statistical dispersal-vicariance
analysis suggest that the ancestral populations were distributed widely on Hainan
Island, and the rising of the central mountainous area of Hainan Island, the
Wuzhi and Yinggeling Mountain Range, separated these four drainages into
independent lineages. According to a spatial analysis of molecular variance
analysis, we divided these populations into three units: ND, CH and WQ + LS,
running into Qiongzhou Strait, the Gulf of Tokin and the South China Sea,
respectively. According to our study, the exposure of straits and shelf under
water retreat gave chances for population dispersion during the glaciations.
PMID- 27606602
TI - Relationship between Research Outcomes and Risk of Bias, Study Sponsorship, and
Author Financial Conflicts of Interest in Reviews of the Effects of Artificially
Sweetened Beverages on Weight Outcomes: A Systematic Review of Reviews.
AB - BACKGROUND: Artificially sweetened beverage consumption has steadily increased in
the last 40 years. Several reviews examining the effects of artificially
sweetened beverages on weight outcomes have discrepancies in their results and
conclusions. OBJECTIVES: To determine whether risk of bias, results, and
conclusions of reviews of effects of artificially sweetened beverage consumption
on weight outcomes differ depending on review sponsorship and authors' financial
conflicts of interest. METHODS: We performed a systematic review of reviews of
the effects of artificially sweetened beverages on weight. Two assessors
independently screened articles for inclusion, extracted data, and assessed risks
of bias. We compared risk of bias, results and conclusions of reviews by
different industry sponsors, authors' financial conflict of interest and journal
sponsor. We also report the concordance between review results and conclusions.
RESULTS: Artificial sweetener industry sponsored reviews were more likely to have
favorable results (3/4) than non-industry sponsored reviews (1/23), RR: 17.25
(95% CI: 2.34 to 127.29), as well as favorable conclusions (4/4 vs. 15/23), RR:
1.52 (95% CI: 1.14 to 2.06). All reviews funded by competitor industries reported
unfavorable conclusions (4/4). In 42% of the reviews (13/31), authors' financial
conflicts of interest were not disclosed. Reviews performed by authors that had a
financial conflict of interest with the food industry (disclosed in the article
or not) were more likely to have favorable conclusions (18/22) than reviews
performed by authors without conflicts of interest (4/9), RR: 7.36 (95% CI: 1.15
to 47.22). Risk of bias was similar and high in most of the reviews. CONCLUSIONS:
Review sponsorship and authors' financial conflicts of interest introduced bias
affecting the outcomes of reviews of artificially sweetened beverage effects on
weight that could not be explained by other sources of bias.
PMID- 27606603
TI - Viruses and Cancer: An Accidental Journey.
PMID- 27606605
TI - Trichilemmal cyst with dermatofibroma-like features on the leg.
PMID- 27606606
TI - Intractable Rectal Pain Secondary to Colonic Stent Placement in Patient With
Advanced Pelvic Cancer Successfully Treated With Hypogastric Nerve Plexus
Neurolysis.
PMID- 27606604
TI - Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple
Determinants of Risk for Congenital Heart Defects.
AB - Elucidating the causes of congenital heart defects is made difficult by the
complex morphogenesis of the mammalian heart, which takes place early in
development, involves contributions from multiple germ layers, and is controlled
by many genes. Here, we use a conditional/invertible genetic strategy to identify
the cell lineage(s) responsible for the development of heart defects in a Nipbl
deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle
transcriptional dysregulation leads to development of atrial septal defects
(ASDs) at high frequency. Using an approach that allows for recombinase-mediated
creation or rescue of Nipbl deficiency in different lineages, we uncover complex
interactions between the cardiac mesoderm, endoderm, and the rest of the embryo,
whereby the risk conferred by genetic abnormality in any one lineage is modified,
in a surprisingly non-additive way, by the status of others. We argue that these
results are best understood in the context of a model in which the risk of heart
defects is associated with the adequacy of early progenitor cell populations
relative to the sizes of the structures they must eventually form.
PMID- 27606607
TI - Does objectively measured daily duration of forward bending predict development
and aggravation of low-back pain? A prospective study.
AB - OBJECTIVES: The aim of this paper was to investigate if objectively measured
daily duration of forward bending of the trunk increases the risk of the
development or aggravation of low-back pain (LBP) over one year in a working blue
collar population by examining (i) the incidence rate of LBP among workers
reporting no LBP at baseline, and (ii) the aggravation of LBP among workers
reporting LBP at baseline. METHODS: Using data from the Danish Physical Activity
Cohort with Objective Measurements (DPhacto), the study measured forward bending
of the trunk (>60) at work (FBW) and during leisure time (FBL), diurnally with
accelerometers, and LBP with one-year monthly self-reports among 682 blue-collar
workers from 15 workplaces. The development of LBP was investigated with Cox's
proportional hazards model (N=200), and the aggravation of LBP was investigated
with mixed model for repeated measurements (N=482). RESULTS: Workers with no LBP
at baseline had a FBW median of 7.9 minutes/day. Workers with LBP at baseline had
a FBW median of 7.3 minutes/day. No significant associations were found between
daily duration of forward bending of the trunk and development or aggravation of
LBP. Similar results were found in the secondary analyses, in which FBL,
different degrees of forward bending (>30 and >90), and varying follow-up time
since measurement were considered. CONCLUSION: Using objective measurements of
forward bending and monthly follow-up of LBP over one year, this study did not
confirm the hypothesis of a positive association between daily duration of
forward bending and LBP.
PMID- 27606608
TI - Can Chronic Sinusitis Cause Cancer?
PMID- 27606609
TI - Immersed Boundary Simulations of Active Fluid Droplets.
AB - We present numerical simulations of active fluid droplets immersed in an external
fluid in 2-dimensions using an Immersed Boundary method to simulate the fluid
droplet interface as a Lagrangian mesh. We present results from two example
systems, firstly an active isotropic fluid boundary consisting of particles that
can bind and unbind from the interface and generate surface tension gradients
through active contractility. Secondly, a droplet filled with an active polar
fluid with homeotropic anchoring at the droplet interface. These two systems
demonstrate spontaneous symmetry breaking and steady state dynamics resembling
cell motility and division and show complex feedback mechanisms with minimal
degrees of freedom. The simulations outlined here will be useful for quantifying
the wide range of dynamics observable in these active systems and modelling the
effects of confinement in a consistent and adaptable way.
PMID- 27606610
TI - The Schnitzler syndrome: chronic urticaria in disguise: a single-centre report of
11 cases and a critical reappraisal of the literature.
AB - OBJECTIVES: The Schnitzler syndrome is a rare inflammatory disorder, with a
chronic urticaria-like rash and an IgM (rarely IgG) monoclonal gammopathy as
cardinal features. Interleukin-1 beta is regarded as the key mediator and the
interleukin-1 receptor antagonist anakinra has been proposed as first-line
treatment. This case series of eleven patients is intended to enhance disease
awareness and to compare our centre's experience with that of literature.
METHODS: We describe the clinical features and disease course of 11 patients with
a definite Schnitzler syndrome, according to the Strasbourg diagnostic criteria,
encountered in the University Hospital, Leuven, Belgium, between 1995 and 2015.
RESULTS: Eleven patients, with a median age of 55 years, were diagnosed with
Schnitzler syndrome. All but one were diagnosed during the last decade. Of 6
patients treated with anakinra, 2 had a suboptimal response and 2 had poor
tolerance (injection site reaction and neutropenia, respectively). Two of the 11
patients died as a consequence of the disease, culminating in Waldenstrom's
macroglobulinaemia and AA amyloidosis, respectively. CONCLUSIONS: The Schnitzler
syndrome is rare, but probably underdiagnosed. In a patient with a chronic
urticaria-like dermatosis, minor itch, intermittent fever and bone or joint
aches, protein electrophoresis and immunofixation should be ordered. Especially,
a finding of a monoclonal IgM kappa fits the diagnosis of Schnitzler syndrome.
Anakinra may provide symptomatic relief, although the response is not always
spectacular. The outcome is not always benign as fatal complications may occur.
PMID- 27606611
TI - Is Beta Radiation Better than 5 Flurouracil as an Adjunct for Trabeculectomy
Surgery When Combined with Cataract Surgery? A Randomised Controlled Trial.
AB - INTRODUCTION: In an African setting surgery is generally accepted as the
treatment of first choice for glaucoma. A problem with trabeculectomy surgery for
the glaucomas is the frequent co-existence and exacerbation of cataract. We
report a randomized controlled trial to compare the use of beta radiation with
5FU in combined cataract and glaucoma surgery. PARTICIPANTS AND METHODS:
Consenting adults aged >40 years with glaucoma, an IOP>21mmHG and cataract were
enrolled and randomised to receive either 1000cG beta radiation application or
sub-conjunctival 5fluorouracil (5FU) at the time of combined trabeculectomy and
phaco-emulsification with lens implant surgery. RESULTS: 385 individuals were
eligible for inclusion of whom 301 consented to inclusion in the study (one eye
per patient). 150 were randomised to the 5FU arm and 151 received beta radiation.
In the 12 months following surgery there were 40 failures (IOP>21mmHg) in the 5FU
arm and 34 failures in the beta arm. The hazard ratio for the beta radiation arm
compared to the 5FU arm, adjusted for IOP at baseline, was 0.83 (95% c.i. 0.54 to
1.28; P = 0.40). The improvement from mean presenting visual acuities of 0.91 and
0.86 logMAR to 0.62 and 0.54 in the 5FU and beta arms respectively was comparable
between groups (P = 0.4 adjusting for baseline VA). Incidence of complications
did not differ between the two groups. DISCUSSION: This study highlights several
important issues in the quest for a therapeutic strategy for the glaucomas in an
African context. Firstly, there is no evidence of an important difference between
the use of 5FU and beta radiation as an anti-metabolite in phacotrabeculectomy.
Secondly phacotrabeculectomy is a successful operation that improves visual
acuity as well as controlling IOP in a majority of patients. Although the success
of trabeculectomy in lowering IOP is reduced when combined with
phacoemulsification compared with trabeculectomy alone, this finding has to be
set against the possible need for subsequent cataract surgery following
trabeculectomy alone, which represents a second trip and expense for the patient
and results in 10-61% failure of the trabeculectomy at one year post-cataract
surgery. TRIAL REGISTRATION: ISRCTN Registry ISRCTN36436933.
PMID- 27606612
TI - Determination of loss of consciousness: a comparison of clinical assessment,
bispectral index and electroencephalogram: An observational study.
AB - BACKGROUND: Computer-processed algorithms of encephalographic signals are widely
used to assess the depth of anaesthesia. However, data indicate that the
bispectral index (BIS), a processed electroencephalography monitoring system, may
not be reliable for assessing the depth of anaesthesia. OBJECTIVE: The aim of
this study was to evaluate the ability of the BIS monitoring system to assess
changes in the level of unconsciousness, specifically during the transition from
consciousness to unconsciousness, in patients undergoing total intravenous
anaesthesia with propofol. We compared BIS with the electroencephalogram (EEG),
and clinical loss of consciousness (LOC) defined as loss of verbal commands and
eyelash reflex. DESIGN: This was an observational cohort study. SETTING:
University Hospital Linkoping, University Hospital Orebro, Finspang Hospital and
Kalmar Hospital, Sweden from October 2011 to April 2013. PATIENTS: A total of 35
ASA I patients aged 18 to 49 years were recruited. INTERVENTIONS: The patients
underwent total intravenous anaesthesia with propofol and remifentanil for
elective day-case surgery. Changes in clinical levels of consciousness were
assessed by BIS and compared with assessment of stage 3 neurophysiological
activity using the EEG. The plasma concentrations of propofol were measured at
clinical LOC and 20 and 30 min after LOC. MAIN OUTCOME MEASURES: The primary
outcome was measurement of BIS, EEG and clinical LOC. RESULTS: The median BIS
value at clinical LOC was 38 (IQR 30 to 43), and the BIS values varied greatly
between patients. There was no correlation between BIS values and EEG stages at
clinical LOC (r = -0.1, P = 0.064). Propofol concentration reached a steady state
within 20 min. CONCLUSION: There was no statistically significant correlation
between BIS and EEG at clinical LOC. BIS monitoring may not be a reliable method
for determining LOC. CLINICAL TRIALS REGISTRY: This trial was not registered
because registration was not mandatory at the time of the trial.
PMID- 27606613
TI - Influence of preoperative oral rehydration on arterial plasma rocuronium
concentrations and neuromuscular blocking effects: A randomised controlled trial.
AB - BACKGROUND: The influence of preoperative rehydration on the action of rocuronium
has not yet been investigated. OBJECTIVE: The objective is to evaluate the
hypothesis that preoperative rehydration lowers arterial rocuronium plasma
concentrations and changes its associated neuromuscular blocking effects during
induction of anaesthesia. DESIGN: Randomised, single-blinded study. SETTING: A
secondary hospital from October 2013 to July 2014. PATIENTS: In total, 46 men
undergoing elective surgery were eligible to participate and were randomly
allocated into two groups. Exclusion criteria were severe hepatic, renal or
cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium;
BMI more than 30 kg m; receiving medication known to influence neuromuscular
function. INTERVENTION: Participants received 1500 ml of oral rehydration
solution (rehydration group) or none (control group) until 2 hours before
anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min
after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia.
Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle
using acceleromyography. MAIN OUTCOME MEASURES: Arterial plasma rocuronium
concentrations. RESULTS: Arterial plasma rocuronium concentrations at 60, 90 and
120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and
6.2 and 8.1 MUg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the
onset times in the rehydration and control groups were 92.0 and 69.5 s (P =
0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004),
respectively. CONCLUSION: Preoperative rehydration significantly reduces arterial
plasma rocuronium concentrations in the first 2 minutes after administration,
prolonging the onset time and shortening the duration of effect. A higher dose or
earlier administration should be considered for patients who receive preoperative
rehydration. TRIAL REGISTRATION: Umin identifier: UMIN000011981.
PMID- 27606614
TI - Periodic Mechanical Stress Activates PKCdelta-Dependent EGFR Mitogenic Signals in
Rat Chondrocytes via PI3K-Akt and ERK1/2.
AB - BACKGROUND/AIMS: The present study aimed to analyze the mechanisms by which
periodic mechanical stress is translated into biochemical signals, and to verify
the important role of signaling molecules including phosphatidylinositol-3-kinase
(PI3K)-Akt, protein kinase C (PKC), and epidermal growth factor receptor (EGFR)
in chondrocyte proliferation. The effects of periodic mechanical stress on the
mitogenesis of chondrocytes have been studied extensively in recent years.
However, the mechanisms underlying the ability of chondrocytes to sense and
respond to periodic mechanical stress need further investigation. METHODS: Two
steps were undertaken in the experiment. In the first step, the cells were
pretreated with shRNA targeted to Akt or EGFR or PKCdelta or control scrambled
shRNA. Moreover, they were pretreated with LY294002, GF109203X, Go6976,
rottlerin, and AG1478. They were maintained under static conditions or periodic
mechanical stress for 3 days, 8 h per day, prior to direct cell counting and CCK
8 assay, respectively. In the second step, the cells were pretreated with shRNA
targeted to Akt or EGFR or PKCdelta or control scrambled shRNA. Moreover, they
were pretreated with LY294002, AG1478, and rottlerin. They were maintained under
static conditions or periodic mechanical stress for 1 h prior to Western blot
analysis. RESULTS: Proliferation was inhibited by pretreatment with PKC or
PKCdelta inhibitor GF109203X or rottlerin and by short hairpin RNA (shRNA)
targeted to PKCdelta, but not by PKCalpha inhibitor Go6976 in chondrocytes in
response to periodic mechanical stress. Meantime, rottlerin and shRNA targeted to
PKCdelta also attenuated EGFR, Akt, and ERK1/2 activation. Furthermore,
inhibiting EGFR activity by AG1478 and shRNA targeted to EGFR abrogated
chondrocyte proliferation and phosphorylation levels of Akt and extracellular
signal-regulated kinase (ERK)1/2 subjected to periodic mechanical stress, while
the phosphorylation site of PKCdelta was not affected. In addition, pretreatment
with the PI3K-Akt-selective inhibitor LY294002 and shRNA targeted to Akt reduced
periodic mechanical stress-induced chondrocyte proliferation and phosphorylation
of ERK1/2, while the phosphorylation levels of EGFR and PKCdelta were not
inhibited. CONCLUSION: These findings suggested that periodic mechanical stress
promoted chondrocyte proliferation through PKCdelta-EGFR-PI3K-Akt-ERK1/2. They
provide a stronger viewpoint for further investigations into chondrocyte
mechanobiology under periodic mechanical stress and the ways to improve the
quality of tissue-engineered cartilage.
PMID- 27606616
TI - [COPD und Klangtherapie: Pilotstudie zur Wirksamkeit einer Behandlung mit
Korpertambura bei COPD-Patienten].
AB - Hintergrund: Erkrankungen der Atemorgane treten mit steigendem Alter ofter auf,
nehmen weltweit zu und sind haufige Ursachen fur Morbiditat und Mortalitat. In
dieser Pilotstudie wurde der Frage nachgegangen, ob eine einmalige 10-minutige
Behandlung mit einer Korpertambura eine signifikante und effektive Verbesserung
der Lungenfunktion von Patienten mit chronisch-obstruktiver Lungenerkrankung
(COPD; GOLD-Stadium A oder B) erbringen kann. Patienten und Methoden: 54
Probanden konnten je zur Halfte in eine Behandlungsgruppe (Korpertambura) und
eine aktive Kontrollgruppe (Atemtherapie) randomisiert werden. Eine Bestimmung
der Lungenfunktionsmessparameter "Einsekundenkapazitat" (FEV1) und
"inspiratorische Vitalkapazitat" (IVC) zu den Zeitpunkten T1 (Baseline), T2
(direkt nach Behandlung) und als Follow-up etwa 3 Wochen nach T1 (T3).
Ergebnisse: Die Behandlungsgruppe zeigte sich der Kontrollgruppe in beiden Werten
signifikant uberlegen. Die Zeit-*-Gruppe-Interaktion (Varianzanalyse) ergab p =
0,001 (FEV1) bzw. p = 0,04 (IVC). Die Behandlungsgruppe zeigte bei beiden Werten
eine Verbesserung von klinischer Relevanz. Schlussfolgerung: Diese Ergebnisse
zeigen, dass die Klangbehandlung mittels einer Korpertambura - neben den
schulmedizinischen, leitliniengerechten Therapien - eine zusatzliche,
nebenwirkungsarme, aber durchaus klinisch wirksame Option fur die Behandlung von
COPD-Patienten darstellen kann, um deren Lebensqualitat zu stabilisieren und zu
verbessern.
PMID- 27606615
TI - Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in
Rheumatoid Arthritis Patients during the First 6 Months of Treatment with
Adalimumab or Infliximab: A Descriptive Cohort Study.
AB - OBJECTIVES: With the present study we wanted to explore the impact of treatment
with a tumor necrosis factor-alpha -inhibitor (TNFi) on levels of soluble
biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of
impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs).
METHODS: Blood samples from 26 patients with established RA were taken at
baseline and following 6 months of treatment with adalimumab or infliximab.
Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF
receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical
and demographic data were recorded as well. RESULTS: During the initial 6 months
treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive
protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients
without anti-TNFi Abs and in patients retaining detectable drug levels. The
levels of other tested cytokines (TNF-alpha, TNF-beta, IL-1ra, IL-1b, IL-8, IL
10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection
limits. Higher baseline levels of IL-6 associated with undetectable levels of
TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but
no predictors for anti-TNFi Ab development could be found. CONCLUSION: The effect
of treatment with TNFi on RA disease activity depends on levels of active drug,
and by presence of anti-TNFi Abs. In patients who retain detectable drug levels,
and in the absence of anti-TNFi Abs, clinical outcome is improved during
treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels
of IL-6 may predict depletion of TNFi and may identify patients at risk of
treatment failure.
PMID- 27606617
TI - Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly
Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.
AB - Whether the level of education is associated with anticoagulation quality and
clinical outcomes in patients with acute venous thromboembolism (VTE) is
uncertain. We thus aimed to investigate the association between educational level
and anticoagulation quality and clinical outcomes in elderly patients with acute
VTE. We studied 817 patients aged >=65 years with acute VTE from a Swiss
prospective multicenter cohort study (09/2009-12/2013). We defined three
educational levels: 1) less than high school, 2) high school, and 3) post
secondary degree. The primary outcome was the anticoagulation quality, expressed
as the percentage of time spent in the therapeutic INR range (TTR). Secondary
outcomes were the time to a first recurrent VTE and major bleeding. We adjusted
for potential confounders and periods of anticoagulation. Overall, 56% of
patients had less than high school, 25% a high school degree, and 18% a post
secondary degree. The mean percentage of TTR was similar across educational
levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P
= 0.36). Within three years of follow-up, patients with less than high school,
high school, and a post-secondary degree had a cumulative incidence of recurrent
VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of
13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was
neither associated with anticoagulation quality nor with recurrent VTE or major
bleeding. In elderly patients with VTE, we did not find an association between
educational level and anticoagulation quality or clinical outcomes.
PMID- 27606619
TI - Agroforestry Practices Promote Biodiversity and Natural Resource Diversity in
Atlantic Nicaragua.
AB - Tropical forest conversion to pasture, which drives greenhouse gas emissions,
soil degradation, and biodiversity loss, remains a pressing socio-ecological
challenge. This problem has spurred increased interest in the potential of small
scale agroforestry systems to couple sustainable agriculture with biodiversity
conservation, particularly in rapidly developing areas of the tropics. In
addition to providing natural resources (i.e. food, medicine, lumber),
agroforestry systems have the potential to maintain higher levels of biodiversity
and greater biomass than lower diversity crop or pasture systems. Greater plant
diversity may also enhance soil quality, further supporting agricultural
productivity in nutrient-limited tropical systems. Yet, the nature of these
relationships remains equivocal. To better understand how different land use
strategies impact ecosystem services, we characterized the relationships between
plant diversity (including species richness, phylogenetic diversity, and natural
resource diversity), and soil quality within pasture, agroforests, and secondary
forests, three common land use types maintained by small-scale farmers in the
Pearl Lagoon Basin, Nicaragua. The area is undergoing accelerated globalization
following the 2007 completion of the region's first major road; a change which is
expected to increase forest conversion for agriculture. However, farmer
agrobiodiversity maintenance in the Basin was previously found to be positively
correlated with affiliation to local agricultural NGOs through the maintenance of
agroforestry systems, despite these farmers residing in the communities closest
to the new road, highlighting the potential for maintaining diverse agroforestry
agricultural strategies despite heightened globalization pressures. We found that
agroforestry sites tended to have higher surface soil %C, %N, and pH relative to
neighboring to secondary forest, while maintaining comparable plant diversity. In
contrast, pasture reduced species richness, phylogenetic diversity, and natural
resource diversity. No significant relationships were found between plant
diversity and the soil properties assessed; however higher species richness and
phylodiversity was positively correlated with natural resource diversity. These
finding suggest that small, diversified agroforestry systems may be a viable
strategy for promoting both social and ecological functions in eastern Nicaragua
and other rapidly developing areas of the tropics.
PMID- 27606618
TI - Translation Regulation and RNA Granule Formation after Heat Shock of Procyclic
Form Trypanosoma brucei: Many Heat-Induced mRNAs Are also Increased during
Differentiation to Mammalian-Infective Forms.
AB - African trypanosome procyclic forms multiply in the midgut of tsetse flies, and
are routinely cultured at 27 degrees C. Heat shocks of 37 degrees C and above
result in general inhibition of translation, and severe heat shock (41 degrees C)
results in sequestration of mRNA in granules. The mRNAs that are bound by the
zinc-finger protein ZC3H11, including those encoding refolding chaperones, escape
heat-induced translation inhibition. At 27 degrees C, ZC3H11 mRNA is
predominantly present as an untranslated cytosolic messenger ribonucleoprotein
particle, but after heat shocks of 37 degrees C-41 degrees C, the ZC3H11 mRNA
moves into the polysomal fraction. To investigate the scope and specificities of
heat-shock translational regulation and granule formation, we analysed the
distributions of mRNAs on polysomes at 27 degrees C and after 1 hour at 39
degrees C, and the mRNA content of 41 degrees C heat shock granules. We found
that mRNAs that bind to ZC3H11 remained in polysomes at 39 degrees C and were
protected from sequestration in granules at 41 degrees C. As previously seen for
starvation stress granules, the mRNAs that encode ribosomal proteins were
excluded from heat-shock granules. 70 mRNAs moved towards the polysomal fraction
after the 39 degrees C heat shock, and 260 increased in relative abundance.
Surprisingly, many of these mRNAs are also increased when trypanosomes migrate to
the tsetse salivary glands. It therefore seems possible that in the wild,
temperature changes due to diurnal variations and periodic intake of warm blood
might influence the efficiency with which procyclic forms develop into mammalian
infective forms.
PMID- 27606621
TI - Mechanically Viscoelastic Properties of Cellulose Nanocrystals Skeleton
Reinforced Hierarchical Composite Hydrogels.
AB - With inspiration from the concept of natural dynamic materials, binary-component
composite hydrogels with excellent mechanical properties and recovery capability
were prepared from the cellulose nanocrystal (CNC) skeleton reinforced covalently
cross-linked polyacrylamide (PAAm) networks. The hierarchical skeleton obtained
by freeze-drying of CNC aqueous suspension was directly impregnated into
acrylamide (AAm) monomer solution, and in situ polymerization occurred in the
presence of hydrophilic cross-linker PEGDA575. Under stress, hydrogen bonds at
the interface between CNC and PAAm as well as inside the CNC skeleton acted as
sacrificial bonds to dissipate energy, while the covalently cross-linked PAAm
chains bind the network together by providing adhesion to CNC and thereby
suppress the catastrophic craze propagation. The above synergistic effects of the
CNC skeleton and the elastic PAAm network enabled the composite hydrogels to
withstand up to 181 kPa of tensile stress, 1.01 MPa of compressive strength, and
1392% elongation at break with the fracture energy as high as 2.82 kJ/m(2).
Moreover, the hydrogels recovered more than 70% elasticity after eight loading
unloading cycles, revealing excellent fatigue resistance. The depth-sensing
instrumentation by indentation test corroborated that the CNC skeleton
contributed simultaneous improvements in hardness and elasticity by as much as
500% in comparison with the properties of the pristine PAAm hydrogels. This
elegant strategy by using the CNC skeleton as a reinforcing template offers a new
perspective for the fabrication of robust hydrogels with exceptional mechanical
properties that may be important for biomedical applications where high strength
is required, such as scaffolds for tissue engineering.
PMID- 27606620
TI - Reconfiguring the AR-TIF2 Protein-Protein Interaction HCS Assay in Prostate
Cancer Cells and Characterizing the Hits from a LOPAC Screen.
AB - The continued activation of androgen receptor (AR) transcription and elevated
expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator
observed in prostate cancer (CaP) recurrence and the development of castration
resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors
of AR-TIF2 protein-protein interactions (PPIs) to find new drug candidates. Small
molecules can elicit tissue selective effects, because the cells of distinct
tissues express different levels and cohorts of coregulatory proteins. We
reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to
determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in
U-2 OS cells would behave differently in the CaP cell background. Although we did
not observe any significant differences in the compound responses between the
assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay
would be more amenable to screening, because both the virus and cell culture
demands are lower. We implemented a testing paradigm of counter-screens and
secondary hit characterization assays that allowed us to identify and
deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional
activation (AR-TA) through antagonism of AR ligand binding or by non-specifically
blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor
molecules act distally to AR ligand binding, they have the potential to modulate
AR-TA in a cell-specific manner that is distinct from existing anti-androgen
drugs, and to overcome the development of resistance to AR antagonism. We
anticipate that the application of this testing paradigm to characterize the hits
from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize
the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed
into novel therapeutics for CaP and CRPC.
PMID- 27606622
TI - The Hole and the Whole: Lessons from Manipulation of Nipbl Deficiency.
AB - Congenital heart defects (CHDs) affect 2%-3% of newborns and remain challenging
clinically. There is an ongoing project to elucidate the causes of CHDs, focusing
primarily on genetics as dictated by the epidemiology. In a paper published in
this issue, Santos and colleagues describe studies of Cornelia de Lange syndrome
associated secundum atrial septal defects (ASDs) caused by NIPBL mutations,
undertaken with a targeted trapping allele in mice. They show that Nipbl
haploinsufficiency in either of two cell populations was sufficient to engender
ASDs but that expression solely in either one of those populations was sufficient
to rescue them. This work provides novel insights into incomplete penetrance and
oligogenic effects underlying CHDs.
PMID- 27606623
TI - The Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Initially
Clinically Node-Negative Breast Cancer after Neoadjuvant Chemotherapy: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: With the increased use of neoadjuvant chemotherapy (NAC) in breast
cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly
important. In this study, we aimed to evaluate the feasibility and accuracy of
SLNB for initially clinically node-negative breast cancer after NAC by conducting
a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, and
the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on
initially clinically node-negative breast cancer patients who underwent SLNB
after NAC followed by axillary lymph node dissection (ALND). RESULTS: A total of
1,456 patients from 16 studies were included in this review. The pooled
identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%
97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled
sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95%
CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%
100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant
differences were found in either the IR of an SLNB when different mapping methods
were used (P = 0.180) or in the FNR between studies with and without
immunohistochemistry (IHC) staining (P = 0.241). CONCLUSION: Based on current
evidence, SLNB is technically feasible and accurate enough for axillary staging
in initially clinically node-negative breast cancer patients after NAC.
PMID- 27606624
TI - Breastfeeding Duration and Childhood Caries: A Cohort Study.
AB - This cohort study was conducted in Khon Kaen, Thailand, to test the hypothesis
that a longer breastfeeding duration increases the risk for dental caries in
primary teeth. We collected information on infant feeding practices and potential
confounders using a structured questionnaire to interview mothers or caregivers
during the second trimester of pregnancy and after birth at 21 days and at 3, 12,
18, 24, and 36 months. Regardless of other liquids and foods, full breastfeeding
was defined as feeding breast milk but not formula, while any breastfeeding was
feeding breast milk with or without formula. Two calibrated dentists measured
dental caries when the children were 3-4 years of age using the decayed, missing,
and filled surfaces (dmfs) index following the World Health Organization
criteria. Negative binomial regression with a generalized linear model was used
to estimate relative risks (RRs) and 95% confidence intervals (CIs) using dmfs as
an outcome. Log-binomial regression was performed to model the caries prevalence.
Of 556 children, 88.1% had dental caries with a mean dmfs of 14.2. Full
breastfeeding for 6-11 months was significantly associated with a lower dmfs
(adjusted RR 0.77, 95% CI 0.63, 0.93) and a lower caries prevalence (adjusted RR
0.45, 95% CI 0.22, 0.90). The frequency of sleeping while breast- or bottle
feeding increased the caries risk in a dose-response manner. There was no
association between duration of any breastfeeding and dental caries. In
conclusion, full breastfeeding for 6-11 months may protect against dental caries
in primary teeth. Prolonged breastfeeding was not associated with dental caries
in this population.
PMID- 27606625
TI - Dimethyloxalylglycine Promotes Bone Marrow Mesenchymal Stem Cell Osteogenesis via
Rho/ROCK Signaling.
AB - BACKGROUND/AIMS: We investigated the role of dimethyloxalylglycine (DMOG) in bone
marrow mesenchymal stem cell (BMSC) osteogenesis mediated by RhoA/ROCK. METHODS:
BMSCs were cultured with and without DMOG and/or Y-27632 (ROCK1 inhibitor). Cell
proliferation, alkaline phosphatase (ALP) levels, and calcium deposits were
determined. The expression of Runx2, OSX, p-cofilin, RhoA, and GTP-bound RhoA was
determined by real-time RT-PCR and Western blot. Rho-associated coiled-coil
containing protein kinase (ROCK) activity was determined by measuring the
phosphorylation of myosin-binding subunit of myosin phosphatase using an ELISA
kit. Actin morphology was observed by immunofluorescence. RESULTS: After 24 h,
DMOG (0.5 mM) increased the expression of GTP-bound RhoA (+141%, P < 0.001) and
enhanced ROCK activity (315%, P < 0.001). DMOG (0.5 mM) enhanced ALP levels after
3, 7, and 21 days of osteogenic induction (all P < 0.001) and strengthened
calcium deposition (P < 0.001). In addition, compared with controls, DMOG (0.5
mM) increased the mRNA levels of osteogenesis genes RUNX2 and OSX (all P <
0.001). Furthermore, compared with controls, DMOG increased the expression of p
cofilin (+57%, P < 0.001), which resulted in rearrangement of actin filaments.
All these effects were abolished, at least in part, by Y-27632. CONCLUSION: DMOG
promotes BMSC osteogenic differentiation via activation of RhoA/ROCK, suggesting
clues for future therapies using BMSCs.
PMID- 27606626
TI - Estimation of Disability Weights in the General Population of South Korea Using a
Paired Comparison.
AB - We estimated the disability weights in the South Korean population by using a
paired comparison-only model wherein 'full health' and 'being dead' were included
as anchor points, without resorting to a cardinal method, such as person trade
off. The study was conducted via 2 types of survey: a household survey involving
computer-assisted face-to-face interviews and a web-based survey (similar to that
of the GBD 2010 disability weight study). With regard to the valuation methods,
paired comparison, visual analogue scale (VAS), and standard gamble (SG) were
used in the household survey, whereas paired comparison and population health
equivalence (PHE) were used in the web-based survey. Accordingly, we described a
total of 258 health states, with 'full health' and 'being dead' designated as
anchor points. In the analysis, 4 models were considered: a paired comparison
only model; hybrid model between paired comparison and PHE; VAS model; and SG
model. A total of 2,728 and 3,188 individuals participated in the household and
web-based survey, respectively. The Pearson correlation coefficients of the
disability weights of health states between the GBD 2010 study and the current
models were 0.802 for Model 2, 0.796 for Model 1, 0.681 for Model 3, and 0.574
for Model 4 (all P-values<0.001). The discrimination of values according to
health state severity was most suitable in Model 1. Based on these results, the
paired comparison-only model was selected as the best model for estimating
disability weights in South Korea, and for maintaining simplicity in the
analysis. Thus, disability weights can be more easily estimated by using paired
comparison alone, with 'full health' and 'being dead' as one of the health
states. As noted in our study, we believe that additional evidence regarding the
universality of disability weight can be observed by using a simplified
methodology of estimating disability weights.
PMID- 27606627
TI - Immunological Profile in Individuals with Schistosomal Myeloradiculopathy.
AB - BACKGROUND: Schistosomal myeloradiculopathy (SMR) is the most serious ectopic
presentation of Schistosoma mansoni infection. The pathogenesis occurs mainly via
the host inflammatory response to the eggs of the parasite that are stuck in the
central nervous system, and the diagnosis is generally made by the exclusion of
other neurological diseases. OBJECTIVE: We aimed to evaluate the immune status of
SMR patients and to identify a marker for SMR diagnosis. METHODS: We enrolled 15
patients with a presumptive diagnosis of SMR, and the control groups included 17
patients with myelopathy associated with human T cell lymphotropic virus type 1
(HTLV-1) and 11 with other neurological disorders. The determination of soluble
egg antigen-specific IgE and the levels of cytokines from Th1, Th2, Th17 and T
regulatory cell profiles and the chemokines MIP-1a and RANTES were measured in
the cerebrospinal fluid (CSF) and serum using an ELISA technique. RESULTS: We
observed that SMR leads to an increase in IgE levels in the CSF compared to
serum, and the levels of IL-13 and MIP-1alpha were significantly higher in the
CSF and serum of the SMR patients than in the patients with HTLV-1-associated
myelopathy. The levels of MIP-1alpha and RANTES were higher in the CSF than in
the serum of the SMR group. The ratio between levels of IL-13, MIP-1alpha and
RANTES over IL-10 was positive in the CSF of the SMR patients. CONCLUSIONS: These
results indicate that S. mansoni-specific IgE in the CSF is a promising marker
for the diagnosis of SMR and that the cytokines and chemokines associated with
the Th2 profile may be important factors in the immunopathogenesis of SMR.
PMID- 27606629
TI - Oral health education (advice and training) for people with serious mental
illness.
AB - BACKGROUND: People with serious mental illness not only experience an erosion of
functioning in day-to-day life over a protracted period of time, but evidence
also suggests that they have a greater risk of experiencing oral disease and
greater oral treatment needs than the general population. Poor oral hygiene has
been linked to coronary heart disease, diabetes, and respiratory disease and
impacts on quality of life, affecting everyday functioning such as eating,
comfort, appearance, social acceptance, and self esteem. Oral health, however, is
often not seen as a priority in people suffering with serious mental illness.
OBJECTIVES: To review the effects of oral health education (advice and training)
with or without monitoring for people with serious mental illness. SEARCH
METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (5
November 2015), which is based on regular searches of MEDLINE, EMBASE, CINAHL,
BIOSIS, AMED, PubMed, PsycINFO, and clinical trials registries. There are no
language, date, document type, or publication status limitations for inclusion of
records in the register. SELECTION CRITERIA: All randomised clinical trials
focusing on oral health education (advice and training) with or without
monitoring for people with serious mental illness. DATA COLLECTION AND ANALYSIS:
We extracted data independently. For binary outcomes, we calculated risk ratio
(RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For
continuous data, we estimated the mean difference (MD) between groups and its 95%
CI. We employed a fixed-effect model for analyses. We assessed risk of bias for
included studies and created 'Summary of findings' tables using GRADE. MAIN
RESULTS: We included three randomised controlled trials (RCTs) involving 1358
participants. None of the studies provided useable data for the key outcomes of
not having seen a dentist in the past year, not brushing teeth twice a day,
chronic pain, clinically important adverse events, and service use. Data for
leaving the study early and change in plaque index scores were provided. Oral
health education compared with standard careWhen 'oral health education' was
compared with 'standard care', there was no clear difference between the groups
for numbers leaving the study early (1 RCT, n = 50, RR 1.67, 95% CI 0.45 to 6.24,
moderate-quality evidence), while for dental state: no clinically important
change in plaque index, an effect was found. Although this was statistically
significant and favoured the intervention group, it is unclear if it was
clinically important (1 RCT, n = 40, MD - 0.50 95% CI - 0.62 to - 0.38, very low
quality evidence).These limited data may have implications regarding improvement
in oral hygiene. Motivational interview + oral health education compared with
oral health educationSimilarly, when 'motivational interview + oral health
education' was compared with 'oral health education', there was no clear
difference for the outcome of leaving the study early (1 RCT, n = 60 RR 3.00, 95%
CI 0.33 to 27.23, moderate-quality evidence), while for dental state: no
clinically important change in plaque index, an effect favouring the intervention
group was found (1 RCT, n = 56, MD - 0.60 95% CI - 1.02 to - 0.18 very low
quality evidence). These limited, clinically opaque data may or may not have
implications regarding improvement in oral hygiene. Monitoring compared with no
monitoringFor this comparison, only data for leaving the study early were
available. We found a difference in numbers leaving early, favouring the 'no
monitoring' group (1 RCT, n = 1682, RR 1.07, 95% CI 1.00 to 1.14, moderate
quality evidence). However, these data are problematic. The control denominator
is implied and not clear, and follow-up did not depend only on individual
participants, but also on professional caregivers and organisations - the latter
changing frequently resulting in poor follow-up, but not a good reflection of the
acceptability of the monitoring to patients. For this comparison, no data were
available for 'no clinically important change in plaque index'. AUTHORS'
CONCLUSIONS: We found no evidence from trials that oral health advice helps
people with serious mental illness in terms of clinically meaningful outcomes. It
makes sense to follow guidelines and recommendations such as those put forward by
the British Society for Disability and Oral Health working group until better
evidence is generated. Pioneering trialists have shown that evaluative studies
relevant to oral health advice for people with serious mental illness are
possible.
PMID- 27606628
TI - Use of the Stable Nitrogen Isotope to Reveal the Source-Sink Regulation of
Nitrogen Uptake and Remobilization during Grain Filling Phase in Maize.
AB - Although the remobilization of vegetative nitrogen (N) and post-silking N both
contribute to grain N in maize (Zea mays L.), their regulation by grain sink
strength is poorly understood. Here we use 15N labeling to analyze the dynamic
behaviors of both pre- and post-silking N in relation to source and sink
manipulation in maize plants. The results showed that the remobilization of pre
silking N started immediately after silking and the remobilized pre-silking N had
a greater contribution to grain N during early grain filling, with post-silking N
importance increasing during the later filling stage. The amount of post-silking
N uptake was largely driven by post-silking dry matter accumulation in both grain
as well as vegetative organs. Prevention of pollination during silking had less
effect on post-silking N uptake, as a consequence of compensatory growth of
stems, husk + cob and roots. Also, leaves continuously export N even though grain
sink was removed. The remobilization efficiency of N in the leaf and stem
increased with increasing grain yield (hence N requirement). It is suggested that
the remobilization of N in the leaf is controlled by sink strength but not the
leaf per se. Enhancing post-silking N uptake rather than N remobilization is more
likely to increase grain N accumulation.
PMID- 27606631
TI - The challenge of reducing medication errors in neonatal intensive care units.
PMID- 27606630
TI - Rampant Cheating by Pathogens?
PMID- 27606632
TI - Alcohol consumption in early adolescence and medical care.
PMID- 27606633
TI - Genetic and epigenetic, the case of hypercholesterolemia.
PMID- 27606635
TI - The power of writing in children.
PMID- 27606634
TI - Considerations on infant mortality and its neonatal component.
PMID- 27606636
TI - Symbols and their therapeutic role: Looking for scientific grounds.
PMID- 27606637
TI - Evaluation of neonatal mortality in Buenos Aires City by place of residence and
use of a health system subsector.
AB - INTRODUCTION: Neonatal mortality is the most important component of infant
mortality. Analyzing neonatal mortality is complex and does not depend
exclusively on the health system. In Buenos Aires City (CABA), between2000 and
2012, neonatal mortality rate was lower than the national mean rate but no
changes were recorded. Besides, the difference is narrowing: in 2000, it was 46%
lower but in 2012, it was 21% lower. OBJECTIVE: To assess the relationship among
the place of maternal residence, the use of a health system subsector, and
mortality rate among newborn infants younger than 28 days old in CABA. METHODS:
Cross-sectional, population-based study conducted in 2011 and 2012 using data
from the Office of Vital Records and the Department of Statistics and Surveys of
CABA. RESULTS: A total of 164 837 births were recorded. The ratio of births in
public and private facilities has remained stable; the private subsector accounts
for 57% ofbirths. The ratiobetweenbothsubsectors was also similar in terms of
gender, birthweight, and average gestational age. Neonatal mortalitywas higher
among mothers who lived outside CABA (6.55%o versus 5.42%, odds ratio: 1.21, 95%
confidence interval: 1.07-1.37, p 0.0039). Among mothers living in CABA, neonatal
mortality was higher in the public health subsector (7.8% versus 4.4%, odds
ratio: 1.77, 95% confidence interval: 1.48-2.11, p < 0.001). CONCLUSION: Unlike
any other district in Argentina, CABA has a very high rate of births and deaths
from other jurisdictions, especially from Greater Buenos Aires, which is not
reflected in official statistics that only consider the place of parental
residence.
PMID- 27606638
TI - Alcohol consumption in early adolescence and medical care.
AB - INTRODUCTION: Alcohol consumptionin adolescents is a risky behavior that can be
prevented. Objective. To determine health care and alcohol consumption pattern in
early adolescence and its relation to determinants of health (biological,
environmental, social and health system factors). METHOD: A qualitative
quantitative, crosssectional study was carried out in the four schools belonging
to Popular Council 8 of Mario Gutierrez Ardaya health sector in May, 2013. The
study universe was made up of adolescents aged 10-14. The sample was determined
through a simple randomized sampling. Surveys were administered to adolescents,
parents, educators and senior health staff members to determine alcohol
consumption, medical care quality and level of knowledge on the problem. A
nominal group with health professionals was created. RESULTS: Two hundred and
eighty eight adolescents were included. 54.5% were alcohol users, of which 30.2%
were 10-11 years old. Those classified as low risk were prevailing (55.6%). 100%
of the senior health staff expressed the need for a methodology of care. 90.4% of
education staff considered adolescence as a vulnerable stage. Relatives reported
that there should be adolescent-specific medical appointments (61.8%). The
nominal group's most important opinions were based on the main features that a
consultation for adolescents should have and on the problems hindering proper
care. CONCLUSIONS: Alcohol consumption was considered high and early start
prevailed. Insufficient care to early adolescents who use alcohol was made
evident.
PMID- 27606639
TI - Relationship between genetic and environmental factors and hypercholesterolemia
in children.
AB - INTRODUCTION: Pediatric hypercholesterolemia has increased over the past decades.
Knowing the environmental and genetic factors that have an impact on it would
allow establishing more adequate screening guidelines. OBJETIVES: To determine if
there is an association between genetic and environmental factors and
hypercholesterolemia in children. To assess the predictive qualities of outcome
measures associated with hypercholesterolemia. MATERIAL AND METHODS:
Observational, analytical, cross-sectional study. POPULATION: students from all
schools located in Jovita. Age: >> 6 and < 12 years old. The total cholesterol
level was measured. A survey was administered to parents to assess their family
medical history (FMH) and socioeconomic level (SEL). Weight and height were
recorded to establish nutritional status. A survey was administered to children
to identify their level of physical activity and their eating habits. The
association was assessed by estimating the OR value (p < 0.05). Diagnostic tests
were done to establish outcome measures that predict hypercholesterolemia.
RESULTS: Three hundred and eighty-two students were included. Their mean
cholesterol level was 168 mg/dL, and 13.4% had hypercholesterolemia. A sedentary
lifestyle was observed in 22.8%, and obesity, in 10.5%. A positive FMH, a high/
middle SEL, and obesity were associated with hypercholesterolemia (OR: 2.10, 2.10
and 2.05, respectively). No association was found between physical activity and
fat/cholesterol intake and hypercholesterolemia. A positive FMH and a high/middle
SEL were sensitive enough (75% and 88%) to predict hypercholesterolemia. The
presence of hypercholesterolemia inboth parents in relation to
hypercholesterolemia in their child showed an OR of 9.59, a sensitivity of 73%, a
specificity of 71%, a positive predictive value of 57%, and a negative predictive
value of 83%. CONCLUSIONS: A positive FMH, a high/ middle SEL, and obesity were
associated with hypercholesterolemia in children. The presence of
hypercholesterolemia in both parents was associated with hypercholesterolemia in
their child and showed itself to be a great potential predictor and screening
criterion.
PMID- 27606641
TI - Effect of abdominal muscle training on respiratory muscle strength and forced
expiratory flows in sedentary, healthy adolescents.
AB - INTRODUCTION: Respiratory muscle training is the most commonly used method to
revert respiratory muscle weakness; however, the effect of protocols based on non
respiratory maneuvers has not been adequately studied in the pediatric
population. The objective of this study was to establish the effect of abdominal
muscle training on respiratory muscle strength and forced expiratory flows in
healthy adolescents. METHODS: This was a quasi-experiment. The sample was made up
of healthy adolescents divided into two groups: an experimental group who
completed eight weeks of active abdominal muscle training, and an equivalent
control group. The following indicators were measured: abdominal muscle strength,
maximal inspiratory pressure, maximal expiratory pressure (MEP), peak expiratory
flow, and peak cough flow, before and after protocol completion. A value of p <
0.05 was considered significant. RESULTS: All studied outcome measures increased
significantly in the experimental group but only MEP increased in the control
group. In addition, a higher MEP was observed in the experimental group compared
to the control group at the end of the protocol, together with a greater increase
in MEP and peak expiratory flow. Finally, the increase in MEP was associated with
an increase in cough peak flow in the experimental group but not in the control
group. CONCLUSION: After eight weeks of abdominal muscle training, MEP and peak
expiratory flow increased in healthy (sedentary) adolescents. Such effects were
associated with intervention-induced increases in cough peak flow.
PMID- 27606642
TI - Feeding practices, physical activity, and fitness in Spanish preschoolers:
influence of sociodemographic outcome measures.
AB - INTRODUCTION: Preschool age is critical for the development of adequate eating
and physical activity habits. OBJECTIVE: The purpose of this study was to analyze
the nutritional status, physical activity (PA) and fitness levels in preschool
children in relation to gender and parental sociodemographic outcome measures.
MATERIAL AND METHODS: Preschool children selected from 30 school facilities in
Southern Spain were included. Children's PA and fitness parameters,
anthropometry, and nutritional status, and parental sociodemographic outcome
measures were recorded. RESULTS: A total of 1287 children aged between 3 and 6
years old (643 boys and 644 girls) participated in the study, together with 1267
parents (72.4%: mothers, 27.6%: fathers). Girls had a lower overweight and
obesity rate than boys. Significant differences were observed by gender in the
consumption of certain food: girls ate more dairy products at breakfast and olive
oil, whereas boys ate more fast food and pasta or rice. Boys had a better fitness
level. Children from a lower socioeconomic level had a higher body mass index, a
worse nutritional status, and a lower PA level. Children whose parents had
completed university education had a lower body mass index and a better
nutritional status. CONCLUSIONS: Preschoolers had a high overweight and obesity
rate, and a low PA level, compared to international references. The fitness level
of girls was lower than that observed in boys. Children whose parents had a low
socioeconomic level and no education had a poor nutritional status.
PMID- 27606640
TI - Perinatal factors associated with neonatal mortality in very low birth weight
infants: a multicenter study.
AB - INTRODUCTION: Objectives. To assess risk factors associated withneonatal
mortality in very low birth weight (VLBW) infants (< 1500 g) and the impact of
the administration of antenatal corticosteroids. POPULATION AND METHODS:
Retrospective analysis of a VLBW infant cohort from 26 tertiary care and teaching
sites member of the South American Neonatal Network (NEOCOSUR), which includes
Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay, conducted between 2000 and
2011 on 11 455 records. Maternal and neonatal characteristics and morbidity were
compared between deceased VLBW infants and those who survived to discharge.
Outcome measures associated with neonatal mortality were established by logistic
regression. The effect of antenatal corticosteroids on neonatal morbidity and
mortality was estimated using the matching method. RESULTS: The neonatal
mortality rate was 22.3%, and variability among sites was elevated. Factors that
were independently associated with a lower mortality of VLBW infants included the
administration of antenatal corticosteroids (OR: 0.49, 95% CI: 0.43-0.54), a
better birth weight Z-score (OR: 0.63, 0.61-0.65), arterial hypertension (OR:
0.67, 0.58-0.77), and C-section (OR: 0.75, 0.65-0.85). The matching method
allowed reducing the risk of death by 38% in association with antenatal
corticosteroids. CONCLUSIONS: Major perinatal factors were identified in
association with neonatal mortality in VLBW infants, and the impact of antenatal
corticosteroid use in the NEOCOSUR Network was demonstrated.
PMID- 27606643
TI - Validation of the Spanish-language version of the Rapid Assessment for Adolescent
Preventive Services among Colombian adolescents.
AB - Seventy percent of adolescent morbidity and mortality is related to six risky
behaviors. The Rapid Assessment for Adolescent Preventive Services is a screening
questionnaire consisting of 21 questions but there is not a validated Spanish
language version. The obj ective of this study was to validate the Spanish
language version of the Rapid Assessment for Adolescent Preventive Services in
two Colombian cities: Bucaramanga and Medellin. The questionnaire was
administered to 270 randomly selected adolescent students aged between 11 and 19
years old. Its internal consistency measured using Cronbach's alpha was 0.7207.
The factor analysis showed that two factors accounted for 84.5% of variance, but
factor loading indicates that only one of these is valid in Colombia: substance
use (tobacco, alcohol, narcotics, and psychoactive substances).
PMID- 27606644
TI - Urinary levels of early kidney injury molecules in children with vitamin B12
deficiency.
AB - The aim of this study was to investigate urine early kidney injury molecules,
including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding
protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase
associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency
(CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls
were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes,
B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR)
was calculated. Urine protein, electrolytes, andurinary early markers were
measured. Patients with CD had significantly higher urine electrolyte/Cr ratios
(p <0.05). Significantly higher urinary KIM-1/Cr, L-FABP/Cr, NAG/Cr and NGAL/Cr
were found in CD group (p <0.05). Significant negative correlations were found
between levels of serum B12 and urinary markers in the patients (p <0.05).
Increased urinary kidney injury molecules and electrolytes in children with B12
deficiency suggest a possible subclinical renal dysfunction, which cannot be
determined by conventional kidney function tests.
PMID- 27606645
TI - Epilepsy surgery in children and adolescents: Report on 43 cases.
AB - Epilepsy surgery in children with refractory epilepsy is one of the most
effective methods to control seizures. The proper selection and assessment of
surgery candidates is critical for surgical treatment to be adequately effective
and safe. The purpose of this article is to describe our experience with 43
consecutive pediatric patients that underwent epilepsy surgery for refractory
epilepsy between September 2005 and May 2014. Effectiveness, safety, and
prognostic factors were analyzed. The median age was 12 years old at the time of
surgery and 4.5 years old at epilepsy onset, with a latency period of up to 6
years until surgery. Since the surgery, the 43 patients have been in follow-up
for a median of 5.4 years (+/-2.3 years). Resective surgery was performed in 32
patients and hemispherectomy, in 11 patients. To date, 62.8% of patients remain
seizure-free. Abetterprognosis was observed in patients who underwent surgery
with a duration of epilepsy of less than two years and in patients in whom a
complete resection of the epileptogenic zone was achieved.
PMID- 27606646
TI - Children and disabilities: what we call them, think and feel about them.
AB - Disability is a problem that affects more and more children and adolescents. But
in the course of our graduate and postgraduate education, we have received
practically no training in this regard. A pediatrician is the primary care
physician of every child and adolescent, and the above-mentioned lack of training
becomes a hurdle in the care provided to children with disabilities. Our idea of
diversity is clearly determined by our culture and the social and family
environment where we grew up, and is highly influenced by our human and
extracurricular development rather than by our medical training. Every course
involved in professional training should include a subject on disability. As
pediatricians, we should reflect on how we see children with disabilities.
PMID- 27606647
TI - Empathy, burnout and... professional competence. Some reflections.
AB - Disability is a problem that affects more and more children and adolescents. But
in the course of our graduate and postgraduate education, we have received
practically no training in this regard. A pediatrician is the primary care
physician of every child and adolescent, and the above-mentioned lack of training
becomes a hurdle in the care provided to children with disabilities. Our idea of
diversity is clearly determined by our culture and the social and family
environment where we grew up, and is highly influenced by our human and
extracurricular development rather than by our medical training. Every course
involved in professional training should include a subject on disability. As
pediatricians, we should reflect on how we see children with disabilities.
PMID- 27606648
TI - Nutrients and neurodevelopment: lipids.
AB - Nutrients, lipids in particular, make up the central nervous system structure and
play major functional roles: they stimulate development, migration, and nerve
cell differentiation. They are part of gray matter, white matter, nerve nuclei,
and synaptogenesis. Breast milk contains lipids which are crucial for infant
brain development. The lipid profile of breast milk was used as a guideline for
the development of breast milk substitutes. However, to date, no substitute has
matched it. Complementary feeding should include docosahexaenoic acid,
arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and
complex lipids found in milk fat. The lipid composition of breast milk depends on
maternal intake and nutritional status during pregnancy and breast-feeding. It
has a great impact on development. Our goal is to review scientific literature
regarding the role of lipids on infant brain development and the importance of
breast milk lipid composition, maternal diet, and complementary feeding.
PMID- 27606649
TI - [Algorithm for the management of nasal obstruction in neonates and infants].
AB - The main cause of nasal obstruction in neonates and infants is inflammatory or
infectious rhinitis. Congenital, neoplastic, traumatic or iatrogenic causes are
less frequent. The pediatrician will alert to signs and symptoms of diseases less
commonbut serious which should be diagnosed early. We present a proposal of
simple algorithm for the management of unilateral and bilateral nasal obstruction
in neonates and infants. We describe the pathologies that cause nasal respiratory
failure, either those that occur very often or those which are important for
their severity, their guiding symptoms to the presumptive diagnosis, additional
studies and treatment.
PMID- 27606650
TI - [The principle of autonomy in pediatrics under the new Civil and Commercial Code
of the Nation: a communication of the Subcommittee on Clinical Ethics].
PMID- 27606651
TI - [Preschool education impact on child development].
AB - Presumed perinatal ischemic stroke is the term used for cases in which an old
stroke is diagnosed by the consequences of it and not by the acute symptoms. Many
presumed perinatal ischemic strokes have congenital hemiparesis as the first
manifestation, which is usually noticed between the fourth and eighth month of
life as early hand preference. That is why the clear and persistent handedness
developed before one year of age must be assumed as a warning sign of probable
motor sequelae. In this paper we review the medical records of 15 cases of
presumed perinatal ischemic stroke to assess the age at which the consultation
led to the diagnosis, reason for consultation and age at development of
handedness.
PMID- 27606652
TI - [Experience in thyroglossal duct pathology: clinical case series].
AB - The thyroglossal duct cyst pathology represents the second cause of bening
cervical anomalies in childhood. Diagnosis is mainly clinical. Sistrunk (1920)
proposed a surgical technique that is still considered the gold standard for
definitive treatment of this condition. A retrospective study was made including
patients who underwent surgery for thyroglossal duct cyst pathology in our
department between June 2008 and August 2015. In this period, we performed 54
procedures in 45 patients (39 primary cases). Median age was 4.7 years; 14/39
patients (31.1%) had pre-operative infection. All patients were studied with neck
ultrasound. A Sistrunk's procedure was performed in all cases. The global
recurrence rate was 17.8% (8/45).
PMID- 27606653
TI - [Anterior cervical hypertrichosis: case report].
AB - The non-syndromic anterior cervical hypertrichosis (OMIM N degrees 600457) is a
genetic disorder characterized by a patch of hair at the level of the laryngeal
prominence. We present a 12-year-old boy with anterior cervical hypertrichosis
and mild generalized hypertrichosis. He has no neurological, ophthalmological or
skeletal anomalies. The clinical follow up is 10 years.
PMID- 27606654
TI - [Kodamaea ohmeri infection in a newborn with a mediastinal mass].
AB - Invasive fungal infections are a considerable cause of morbidity, mortality,
increased hospital stay durations, and high health care costs, during neonatal
period. In this period, the premature infants are the most affected. Candida
species are the leading cause of invasive fungal infections. The majority of
neonatal Candida infections are caused by C. albicans, C. parapsilosis, C.
glabrata and C. tropicalis, although other fungus species are being reported. One
such emerging pathogen is K. ohmeri. This organism has been reported as a
pathogen in the neonatal period, principally in premature infants. The risk
factors associated with fungal infection are central line, immunosuppression,
prolonged hospital stay, endotracheal intubation and exposure to antibiotics. We
present a term baby with a mediastinal mass, who required several procedures, as
pericardiocentesis, central catheters, mechanical ventilation, antibiotics.
During his evolution, he presented infection by K. ohmeri. The baby was treated
with amphotericin B, with satisfactory clinical course.
PMID- 27606655
TI - [Systemic sarcoidosis: a diagnostic challenge in pediatrics. Case report].
AB - Sarcoidosis is a granulomatous inflammatory disease of unknown etiology,
evidenced most often in young adults, which can compromise several organs, mainly
lung, lymph nodes, eyes and skin. The presence of the disease in pediatric
population is rare. Denomination in pediatrics is made based on age and clinical
manifestations of the patient. The aim of this report is to present a case of
systemic sarcoidosis in a pediatric patient without lung involvement with severe
extrapulmonary manifestations. Fifteen year old patient who debuted with
nonspecific symptoms (emesis, weight loss). Radiographic studies without lung
involvement but with findings suggestive of Langerhans cell histiocytosis;
however, histopathological report (bone and lymph) showed the presence of chronic
granulomatous nonnecrotizing disease, sarcoidosis type. Childhood sarcoidosis is
a rare and difficult entity to diagnose, mainly by the lack of specific
biomarkers for diagnosis.
PMID- 27606656
TI - [Mycobacterium lentiflavum lymphadenitis: two case reports].
AB - Lymphadenitis is the most common clinical feature in nontuberculous mycobacterium
infection in immunocompetent children. We present two case reports of M.
lentiflavum lymphadenitis diagnosed in a tertiary hospital in the last 10 years.
Routine tests were performed after persistent adenopathy, and a sample for
culture was obtained, being positive for this microorganism. Both patients
received oral antibiotics during several weeks. Case 1 needed complete excision
after five months of treatment, whilst Case 2 was cured by medical therapy. M.
lentiflavum is considered, among the newly described nontuberculous mycobacterial
species, an emergent pathogen in our environment. It has its own microbiological
and clinical characteristics, different from the rest of nontuberculous
mycobacteria. Case reports are limited in the literature since the infection was
described for the first time in 1997.
PMID- 27606657
TI - [Psoas abscess and lumbar spine osteomyelitis: case report].
AB - Psoas abscess is a common disease in children. It can have a nonspecific clinical
presentation, insidious onset and sometimes fever. The most common type in
children is the primary one; however, it can sometimes be of secondary origin and
associated with severe infections such as osteomyelitis so a high index of
suspicion is required to detect and treat it promptly. We present an unusual case
of psoas abscess with infiltration of the vertebral body of L2 in a 14 year old
male patient previously healthy with no history of trauma or fever on admission.
X-ray and ultrasound were performed but the diagnosis was confirmed by magnetic
resonance imaging of the lumbosacral spine. With positive blood cultures for
methicillin-resistant Staphylococcus aureus he completed 2 weeks of intravenous
antibiotic therapy and 4 weeks of oral antibiotic therapy with blood cultures
negativization and resolution of symptoms.
PMID- 27606658
TI - [Dentigerous cyst: a case report].
AB - Maxillary cysts are a diverse group of entities that include benign and malignant
odontogenic tumors. Information on the prevalence of this disease is limited. It
is more common among males, and usually occurs in the second and third decade of
life. The proportion of 6 to 7 year old patients with dentigerous cysts is only
9.1%. Dentigerous cysts encompass the crown of a permanent and unerupted impacted
teeth. They are usually slow growing asymptomatic lesions that are not discovered
until they affect surrounding organs. The aim of this study is to present an
unusual case of dentigerous cyst and to inform the pediatrician about the
management of a unilateral maxillary tumor in a healthy child, underlining the
importance of a multidisciplinary approach of this disease.
PMID- 27606659
TI - Bacteremia caused by Rothia mucilaginosa after pneumonia, in a patient with
hematopoietic stem cell transplantation.
AB - Rothia muciloginosa is a member of normal flora and rarely causes invasive
disease. Immunosupressed patients have increased risk for severe infection. Here,
we report a male patient with relapsed neuroblastoma hospitalized for pneumonia.
After clinical improvement, patient's respiratory symptoms worsened again. Rothia
muciloginosa was isolated from blood culture. The worsening of respiratory
symptoms can be explained by hematogenous spread of bacteria. He was successfully
treated with meropenem and vancomycin for 14 days. This rarely seen bacterium is
known to have high mortality rates unless treated appropriately and should be
considered especially in patients with malignancy due to their immunsupressed
situation.
PMID- 27606660
TI - A rare cause of acute abdominal distention: opening of the pancreatic duct into
hydatic cyst.
AB - INTRODUCTION: Hydatid cyst, which is caused by Echinococcus granulosus, is mostly
seen in the liver and lungs although it may also rarely be found in any organ or
soft tissue. This study presents an interesting case of pancreatic hydatid cyst
in which the pancreatic duct opened into this cyst. CASE REPORT: A 10-year-old
boy presented to our clinic with significant abdominal distension and pain in the
epigastric region which had started 10 days previously. Serum amylase level was
3709 U/L and hemagglutination inhibition for hydatid disease was 1/160. At
abdominal computed tomography, two separate lesions and ascites were determined,
a CE2 hydatid cyst in the region of the tail of the pancreas and a CE1 hydatid
cyst in the left lobe of the liver. Percutaneous drainage was applied to the cyst
in the pancreatic tail, and the patient was started on albendazole. The drainage
catheter was removed, and the patient has since been followed-up on an outpatient
basis with no complications.
PMID- 27606661
TI - [Congenital broncho-biliary fistula: a case report].
AB - Congenital tracheo-or-bronchobiliary fistula or congenital he-patopulmonary
fistula is a rare malformation with high morbidity and mortality if the diagnosis
is not made early. The tracheo-or-bronchobiliary fistula is a communication
between the respiratory (trachea or bronchus) and biliary tract. To date, only 35
cases have been published worldwide. We report a case of a neonate with right
pneumonia and bilious fluid in the endotracheal tube. Diagnosis was made using
bronchoscopy with fluoroscopy. Videothoracoscopy was used to remove the
bronchobiliary fistula. Subsequently, a left he-patectomy with Roux-en-Y biliary
digestive anastomosis was performed as bile ductus hypoplasia was present.
PMID- 27606662
TI - Campylobacter jejuni: A rare agent in a child with peritoneal dialysis-related
peritonitis.
AB - Peritonitis is a serious problem in children receiving peritoneal dialysis.
Campylobacter jejuni is an unusual cause of peritonitis. A 10-year-old boy who
had end stage renal failure due to atypical hemolytic uremic syndrome was
admitted to our hospital with abdominal pain and fever. Peritoneal dialysis fluid
was cloudy and microscopic examination showed abundant leukocytes.
Intraperitoneal cefepime treatment was started. Campylobacter jejuni was isolated
from peritoneal dialysis fluid culture and oral clarithromycin was added to the
treatment. At the end of therapy, peritoneal fluid culture was negative. To our
knowledge, C. jejuni peritonitis was not reported in children previously.
CONCLUSION: Although C. jejuni peritonitis is rarely encountered in children, it
should be considered as an etiologic factor for peritonitis.
PMID- 27606663
TI - [Hemophagocytic syndrome associated with tuberculosis in a patient with acquired
immunodeficiency].
AB - The secondary hemophagocytic syndrome is rare in children and even rarer
associated with tuberculosis. e report the case of a patient with acquired
immunodeficiency syndrome, disseminated tuberculosis and hemophagocytic syndrome.
An 8-year-old girl, diagnosed with acquired immunodeficiency syndrome, was
admitted due to fever, vomiting and abdominal pain. She presented abdominal
distension, dehydration, tachypnea, crackles and wheezing in both lungs, anemia,
thrombocytopenia and coagulopathy. She received broad-spectrum antibiotics and
exploratory laparotomy was performed with appendectomy and lymph node biopsy.
After 72 hours the patient presented tonic clonic seizure, impaired sensory,
fever, hypoxemia, hepatosplenomegaly, ascites and peripheral edema. She developed
bicytopenia, hyperferritinemia and bone marrow microscopic examination with
hemophagocytosis. She received intravenous gammaglobulin, steroids and blood
transfusions. Mycobacterium tuberculosis was cultured in gastric aspirate, bone
marrow and abdominal lymph node biopsy. She was treated with isoniazid,
rifampicin, streptomycin and ethambutol, showing marked improvement.
PMID- 27606664
TI - Normal newborn with prenatal suspicion of X chromosome monosomy due to confined
placental mosaicism.
AB - The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal
testing (NIPT) offers pregnant women a more accurate method than traditional
serum screening methods for detecting fetal aneuploidies. Clinical trials have
demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However
NIPT approaches that take advantage of single-nucelotide polymorphism (SNP)
information potentially allow the identification of triploidy, chromosomal
microdeletion syndromes and other unusual genetic variants. To highlight this
approach of NIPT we present a rare case of confined placental X chromosome
monosomy mosaicism that was prenatally suspected with a single-nucleotide
polymorphism-based noninvasive prenatal test. The results of invasive tests
(amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46,
XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX),
confirming that mosaicism was limited to the placenta. These results highlight
the need of patient's informed consent and thorough pretest and postest
counseling to ensure that they understand the limitations and advantages of the
tests and the implications of the resultss.
PMID- 27606665
TI - Preschool education impact on child development.
AB - Henoch-Schonlein purpura (HSP) is the most common vasculitis in children.
Vasculitic processes can involve the lung. Although diffuse alveolar hemorrhage
may be seen as one of the manifestation of HSP, it is not a frequent
presentation. Here we reported the case of a 10-year-old girl with HSP nephritis
who developed pulmonary hemorrhage. The patient was treated successfully with
intravenous methylprednisolone. A review of the literature revealed that young
age may be a good prognostic sign and that immunosuppressive drugs and supportive
management are essential in the treatment.
PMID- 27606666
TI - Pelvic osteomyelitis in a 15-year-old girl: case report.
AB - Pelvic osteomyelitis is a rare infection. Ilium, ischium, pubis and acetabulum
are commonly affected sites. Pelvic radiography, pelvic magnetic resonance and
scintigraphy are useful imaging techniques for diagnosis. However, diagnoses
should be confirmed with bone biopsy from the lesion. Sometimes diagnosis is
delayed because of deep localization of infection site. Here in, we report a 15
year-old girl with left groin pain who was diagnosed as pelvic osteomyelitis one
month after initial symptoms. Patient was successfully treated with antibiotics
for 8 weeks. In conclusion, although pelvic osteomyelitis is an unusual infection
in childhood, it should be considered as differential diagnoses of pain in groin,
hips, thigh, abdomen and spine. If diagnosis is suspicious, empiric treatment
should be started quickly, because it will be possible to achieve satisfactory
clinical results with effective treatment.
PMID- 27606667
TI - [Early handedness: Warning sign of perinatal stroke. Case series].
PMID- 27606668
TI - mTORC1 Signaling Promotes Limb Bud Cell Growth and Chondrogenesis.
AB - mTORC1 signaling has been shown to promote limb skeletal growth through
stimulation of protein synthesis in chondrocytes. However, potential roles of
mTORC1 in prechondrogenic mesenchyme have not been explored. In this study, we
first deleted Raptor, a unique and essential component of mTORC1, in
prechondrogenic limb mesenchymal cells. Deletion of Raptor reduced the size of
limb bud cells, resulting in overall diminution of the limb bud without affecting
skeletal patterning. We then examined the potential role of mTORC1 in
chondrogenic differentiation in vitro. Both pharmacological and genetic
disruption of mTORC1 significantly suppressed the number and size of cartilage
nodules in micromass cultures of limb bud mesenchymal cells. Similarly,
inhibition of mTORC1 signaling in chondrogenic ATDC5 cells greatly impaired
cartilage nodule formation, and decreased the expression of the master
transcriptional factor Sox9, along with the cartilage matrix genes Acan and
Col2a1. Thus, we have identified an important role for mTORC1 signaling in
promoting limb mesenchymal cell growth and chondrogenesis during embryonic
development. J. Cell. Biochem. 118: 748-753, 2017. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27606669
TI - Take-home naloxone treatment for opioid emergencies: a comparison of routes of
administration and associated delivery systems.
AB - INTRODUCTION: Naloxone reversal of opioid-induced respiratory depression outside
of medical facilities has become more prevalent because of the escalating opioid
epidemic in the USA. Take-home naloxone for treatment of opioid emergencies is
now being recommended by numerous federal, state, and professional organizations.
Areas covered: The scope of the opioid overdose epidemic is reviewed along with
practical, clinical, regulatory, and usability considerations for take-home
naloxone routes of administration currently available and associated delivery
systems. Specific opioid-related factors are discussed in detail with emphasis
placed on life-threatening respiratory depression and naloxone antagonism. A
clinical overview, including pharmacokinetic and FDA approval information for
each take-home naloxone product is discussed in detail as well as the impact of
take-home naloxone in the community. Finally, given these products are to be used
in a panic-stricken, life-threatening opioid emergency, an analysis of available
usability data is provided with proposed directions for further study. Expert
opinion: Based on the available clinical evidence, auto-injectable naloxone
should be the preferred administration route for take-home naloxone treatment
until additional safety, efficacy, and comparative outcomes data are available
for unconventional routes of administration that unequivocally provide equal or
superior results.
PMID- 27606670
TI - LEFTYA Activates the Epithelial Na+ Channel (ENaC) in Endometrial Cells via Serum
and Glucocorticoid Inducible Kinase SGK1.
AB - BACKGROUND: Serum & glucocorticoid inducible kinase (SGK1) regulates several ion
channels, including amiloride sensitive epithelial Na+ channel (ENaC). SGK1 and
ENaC in the luminal endometrium epithelium, are critically involved in embryo
implantation, although little is known about their regulation. The present study
explored whether SGK1 and ENaC are modulated by LEFTYA, a negative regulator of
uterine receptivity. METHODS: Expression levels were determined by qRT-PCR and
Western blotting, ENaC channel activity by whole cell patch clamp and
transepithelial current by Ussing chamber experiments. RESULTS: Treatment of
Ishikawa cells, an endometrial adenocarcinoma model cell line of endometrial
epithelial cells, with LEFTYA rapidly up-regulated SGK1 and ENaC transcript and
protein levels. Induction of ENaC in response to LEFTYA was blunted upon co
treatment with the SGK1 inhibitor EMD638683. ENaC levels also significantly
upregulated upon expression of a constitutively active, but not a kinase dead,
SGK1 mutant in Ishikawa cells. LEFTYA increased amiloride sensitive Na+-currents
in Ishikawa cells and amiloride sensitive transepithelial current across the
murine endometrium. Furthermore, LEFTYA induced the expression of ENaC in the
endometrium of wild-type but not of Sgk1-deficient mice. CONCLUSIONS: LEFTYA
regulates the expression and activity of ENaC in endometrial epithelial cells via
SGK1. Aberrant regulation of SGK1 and ENaC by LEFTYA could contribute to the
pathogenesis of unexplained infertility.
PMID- 27606672
TI - [Kommentar zur Originalarbeit "COPD und Klangtherapie: Pilotstudie zur
Wirksamkeit einer Behandlung mit Korpertambura bei COPD-Patienten" von Hartwig et
al].
PMID- 27606671
TI - Characterizing College Science Assessments: The Three-Dimensional Learning
Assessment Protocol.
AB - Many calls to improve science education in college and university settings have
focused on improving instructor pedagogy. Meanwhile, science education at the K
12 level is undergoing significant changes as a result of the emphasis on
scientific and engineering practices, crosscutting concepts, and disciplinary
core ideas. This framework of "three-dimensional learning" is based on the
literature about how people learn science and how we can help students put their
knowledge to use. Recently, similar changes are underway in higher education by
incorporating three-dimensional learning into college science courses. As these
transformations move forward, it will become important to assess three
dimensional learning both to align assessments with the learning environment, and
to assess the extent of the transformations. In this paper we introduce the Three
Dimensional Learning Assessment Protocol (3D-LAP), which is designed to
characterize and support the development of assessment tasks in biology,
chemistry, and physics that align with transformation efforts. We describe the
development process used by our interdisciplinary team, discuss the validity and
reliability of the protocol, and provide evidence that the protocol can
distinguish between assessments that have the potential to elicit evidence of
three-dimensional learning and those that do not.
PMID- 27606674
TI - The LET Procedure for Prosthetic Myocontrol: Towards Multi-DOF Control Using
Single-DOF Activations.
AB - Simultaneous and proportional myocontrol of dexterous hand prostheses is to a
large extent still an open problem. With the advent of commercially and
clinically available multi-fingered hand prostheses there are now more
independent degrees of freedom (DOFs) in prostheses than can be effectively
controlled using surface electromyography (sEMG), the current standard human
machine interface for hand amputees. In particular, it is uncertain, whether
several DOFs can be controlled simultaneously and proportionally by exclusively
calibrating the intended activation of single DOFs. The problem is currently
solved by training on all required combinations. However, as the number of
available DOFs grows, this approach becomes overly long and poses a high
cognitive burden on the subject. In this paper we present a novel approach to
overcome this problem. Multi-DOF activations are artificially modelled from
single-DOF ones using a simple linear combination of sEMG signals, which are then
added to the training set. This procedure, which we named LET (Linearly Enhanced
Training), provides an augmented data set to any machine-learning-based intent
detection system. In two experiments involving intact subjects, one offline and
one online, we trained a standard machine learning approach using the full data
set containing single- and multi-DOF activations as well as using the LET
augmented data set in order to evaluate the performance of the LET procedure. The
results indicate that the machine trained on the latter data set obtains worse
results in the offline experiment compared to the full data set. However, the
online implementation enables the user to perform multi-DOF tasks with almost the
same precision as single-DOF tasks without the need of explicitly training multi
DOF activations. Moreover, the parameters involved in the system are
statistically uniform across subjects.
PMID- 27606673
TI - Characterizing the Syphilis-Causing Treponema pallidum ssp. pallidum Proteome
Using Complementary Mass Spectrometry.
AB - BACKGROUND: The spirochete bacterium Treponema pallidum ssp. pallidum is the
etiological agent of syphilis, a chronic multistage disease. Little is known
about the global T. pallidum proteome, therefore mass spectrometry studies are
needed to bring insights into pathogenicity and protein expression profiles
during infection. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the T.
pallidum proteome profile during infection, we studied T. pallidum ssp. pallidum
DAL-1 strain bacteria isolated from rabbits using complementary mass spectrometry
techniques, including multidimensional peptide separation and protein
identification via matrix-assisted laser desorption ionization-time of flight
(MALDI-TOF/TOF) and electrospray ionization (ESI-LTQ-Orbitrap) tandem mass
spectrometry. A total of 6033 peptides were detected, corresponding to 557 unique
T. pallidum proteins at a high level of confidence, representing 54% of the
predicted proteome. A previous gel-based T. pallidum MS proteome study detected
58 of these proteins. One hundred fourteen of the detected proteins were
previously annotated as hypothetical or uncharacterized proteins; this is the
first account of 106 of these proteins at the protein level. Detected proteins
were characterized according to their predicted biological function and
localization; half were allocated into a wide range of functional categories.
Proteins annotated as potential membrane proteins and proteins with unclear
functional annotations were subjected to an additional bioinformatics pipeline
analysis to facilitate further characterization. A total of 116 potential
membrane proteins were identified, of which 16 have evidence supporting outer
membrane localization. We found 8/12 proteins related to the paralogous tpr gene
family: TprB, TprC/D, TprE, TprG, TprH, TprI and TprJ. Protein abundance was semi
quantified using label-free spectral counting methods. A low correlation (r =
0.26) was found between previous microarray signal data and protein abundance.
CONCLUSIONS: This is the most comprehensive description of the global T. pallidum
proteome to date. These data provide valuable insights into in vivo T. pallidum
protein expression, paving the way for improved understanding of the
pathogenicity of this enigmatic organism.
PMID- 27606676
TI - Influence of Coastal Upwelling on SST Trends along the South Coast of Java.
AB - The south coast of Java has warmed at a much lower rate than adjacent ocean
locations over the last three decades (1982-2015). This behavior can be observed
during the upwelling season (July-October) and it is especially patent in August
and September when upwelling attains the highest values. Although different
warming rates (ocean-coast) had been previously observed in other areas around
the world, this behavior was always linked to situations where upwelling
increased or remained unchanged. South Java warming is observed at ocean
locations and cooling near shore but under a scenario of decreasing upwelling
(~30% in some cases). The origin of coastal cooling is due to changes in the
vertical structure of the water column. A vein of subsurface water, which has
cooled at a rate higher than 0.3 degrees C per decade, is observed to enter from
the northwestern part of the study area following the South Java Current. This
water only manifests at surface near coast, where it is pumped up by coastal
upwelling.
PMID- 27606675
TI - Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated
Poliovirus Vaccine - Worldwide, 2016.
AB - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis,
transmission of the three types of wild poliovirus (WPV) has been sharply reduced
(1). WPV type 2 (WPV2) has not been detected since 1999 and was declared
eradicated in September 2015. Because WPV type 3 has not been detected since
November 2012, WPV type 1 (WPV1) is likely the only WPV that remains in
circulation (1). This marked progress has been achieved through widespread use of
oral poliovirus vaccines (OPVs), most commonly trivalent OPV (tOPV), which
contains types 1, 2, and 3 live, attenuated polioviruses and has been a mainstay
of efforts to prevent polio since the early 1960s. However, attenuated
polioviruses in OPV can undergo genetic changes during replication, and in
communities with low vaccination coverage, can result in vaccine-derived
polioviruses (VDPVs) that can cause paralytic polio indistinguishable from the
disease caused by WPVs (2). Among the 721 polio cases caused by circulating VDPVs
(cVDPVs*) detected during January 2006-May 2016, type 2 cVDPVs (cVDPV2s)
accounted for >94% (2). Eliminating the risk for polio caused by VDPVs will
require stopping all OPV use. The first stage of OPV withdrawal involved a
global, synchronized replacement of tOPV with bivalent OPV (bOPV) containing only
types 1 and 3 attenuated polioviruses, planned for April 18-May 1, 2016, thereby
withdrawing OPV type 2 from all immunization activities (3). Complementing the
switch from tOPV to bOPV, introduction of at least 1 dose of injectable,
trivalent inactivated poliovirus vaccine (IPV) into childhood immunization
schedules reduces risks from and facilitates responses to cVDPV2 outbreaks. All
155 countries and territories that were still using OPV in immunization schedules
in 2015 have reported that they had ceased use of tOPV by mid-May 2016.(?) As of
August 31, 2016, 173 (89%) of 194 World Health Organization (WHO) countries
included IPV in their immunization schedules.(S) The cessation of tOPV use is a
major milestone toward the global goal of eradicating polio; however, careful
surveillance for polioviruses and prompt, aggressive responses to polio outbreaks
are still needed to realize a polio-free world.
PMID- 27606677
TI - Challenges of Estimating the Annual Caseload of Severe Acute Malnutrition: The
Case of Niger.
AB - INTRODUCTION: Reliable prospective estimates of annual severe acute malnutrition
(SAM) caseloads for treatment are needed for policy decisions and planning of
quality services in the context of competing public health priorities and limited
resources. This paper compares the reliability of SAM caseloads of children 6-59
months of age in Niger estimated from prevalence at the start of the year and
counted from incidence at the end of the year. METHODS: Secondary data from two
health districts for 2012 and the country overall for 2013 were used to calculate
annual caseload of SAM. Prevalence and coverage were extracted from survey
reports, and incidence from weekly surveillance systems. RESULTS: The prospective
caseload estimate derived from prevalence and duration of illness underestimated
the true burden. Similar incidence was derived from two weekly surveillance
systems, but differed from that obtained from the monthly system. Incidence
conversion factors were two to five times higher than recommended. DISCUSSION:
Obtaining reliable prospective caseloads was challenging because prevalence is
unsuitable for estimating incidence of SAM. Different SAM indicators identified
different SAM populations, and duration of illness, expected contact coverage and
population figures were inaccurate. The quality of primary data measurement,
recording and reporting affected incidence numbers from surveillance. Coverage
estimated in population surveys was rarely available, and coverage obtained by
comparing admissions with prospective caseload estimates was unrealistic or
impractical. CONCLUSIONS: Caseload estimates derived from prevalence are
unreliable and should be used with caution. Policy and service decisions that
depend on these numbers may weaken performance of service delivery. Niger may
improve SAM surveillance by simplifying and improving primary data collection and
methods using innovative information technologies for single data entry at the
first contact with the health system. Lessons may be relevant for countries with
a high burden of SAM, including for targeted emergency responses.
PMID- 27606679
TI - High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers
in a Clinical Sample with Subjective Cognitive Impairment.
AB - BACKGROUND/AIMS: Subjective cognitive impairment (SCI) is a trigger for seeking
health care in a possible preclinical phase of Alzheimer's disease (AD), although
the characteristics of SCI need clarification. We investigated the prevalence of
psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI
(mild cognitive impairment). METHODS: Memory clinic patients (SCI: n = 90; age:
59.8 +/- 7.6 years; MCI: n = 160; age: 63.7 +/- 7.0 years) included in the
Gothenburg MCI study were examined at baseline. Variables were analyzed using
logistic regression with SCI as dependent variable. RESULTS: Stress was more
prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more
previous depressive symptoms (p = 0.006), but showed no difference compared to
MCI patients considering current depressive symptoms. A positive CSF AD profile
was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001).
Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a
negative CSF AD profile (p = 0.036) predicted allocation to the SCI group.
CONCLUSION: Psychosocial stress is more prevalent in SCI than previously
acknowledged. The high prevalence and long-term occurrence of stress/depressive
symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers
strengthens the notion that AD is not the most likely etiology of SCI.
PMID- 27606678
TI - Steroidogenic Acute Regulatory Protein Overexpression Correlates with Protein
Kinase A Activation in Adrenocortical Adenoma.
AB - The association of pathological features of cortisol-producing adrenocortical
adenomas (ACAs) with somatic driver mutations and their molecular classification
remain unclear. In this study, we explored the association between steroidogenic
acute regulatory protein (StAR) expression and the driver mutations activating
cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling to
identify the pathological markers of ACAs. Immunohistochemical staining for StAR
and mutations in the protein kinase cAMP-activated catalytic subunit alpha
(PRKACA), protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A)
and guanine nucleotide binding protein, alpha stimulating (GNAS) genes were
examined in 97 ACAs. The association of StAR expression with the clinical and
mutational features of the ACAs was analyzed. ACAs with mutations in PRKACA,
GNAS, and PRKAR1A showed strong immunopositive staining for StAR. The concordance
between high StAR expression and mutations activating cAMP/PKA signaling in the
ACAs was 99.0%. ACAs with high expression of StAR had significantly smaller tumor
volume (P < 0.001) and higher urinary cortisol per tumor volume (P = 0.032) than
those with low expression of StAR. Our findings suggest that immunohistochemical
staining for StAR is a reliable pathological approach for the diagnosis and
classification of ACAs with cAMP/PKA signaling-activating mutations.
PMID- 27606680
TI - On chip purification of hiPSC-derived cardiomyocytes using a fishnet-like
microstructure.
AB - Human induced pluripotent stem cells (hiPSCs) can be differentiated at high
efficiency into cells of a targeting type but the resulting cell population has
to be of high purity for clinical therapies to avoid teratomas. Herein, we report
a microfluidic device with integrated and surface functionalised fishnet-like
structures for specific cell capture. With the help of a flow derivation surface
pattern, cells in solution are forced to cross the fishnet-like structure,
resulting in high efficiency and selective retention of a chosen cell population.
A suspension of hiPSCs and hiPSC-derived cardiomyocytes were used for device
function validation. We found that a hiPSC capture rate over 80% can be achieved
along with a remarkable increase in the CM population rate in the recovered
suspension without affecting cell viability.
PMID- 27606681
TI - Findings of Optical Coherence Tomographic Angiography at the Choriocapillaris
Level in Central Serous Chorioretinopathy.
AB - PURPOSE: To reveal vascular signals at the choriocapillaris level in central
serous chorioretinopathy (CSC) using optical coherence tomographic angiography
(OCTA). PROCEDURES: We analyzed vascular signals at the choriocapillaris level in
58 CSC and 51 contralateral eyes by OCTA (RTVue XR Avanti with AngioVue; Optovue
Inc., Fremont, Calif., USA). Data analysis included age, best corrected visual
acuity (BCVA), disease duration and serous retinal detachment (SRD) height.
RESULTS: Morphologically, abnormal signals at the choriocapillaris level were
detected in all CSC eyes (100%), and then classified into three patterns. Age,
BCVA, disease duration and SRD height showed no significant correlation with
signal patterns. Thirty-one contralateral eyes (61%) showed abnormal signals at
the choriocapillaris level on OCTA, while 20 (39%) had a normal pattern.
CONCLUSIONS: OCTA revealed three types of abnormal signals not only in CSC eyes
but also in fellow eyes without SRD. OCTA may provide information for elucidating
the underlying pathogenesis of CSC.
PMID- 27606682
TI - Ethnic and regional differences in STI clinic use: a Dutch epidemiological study
using aggregated STI clinic data combined with population numbers.
AB - OBJECTIVES: Ethnic minorities (EM) from STI-endemic countries are at increased
risk to acquire an STI. The objectives of this study were to investigate the
difference in STI clinic consultation and positivity rates between ethnic groups,
and compare findings between Dutch cities. METHODS: Aggregated population numbers
from 2011 to 2013 of 15-44 year-old citizens of Amsterdam, Rotterdam, The Hague
and Utrecht extracted from the population register (N=3 129 941 person-years)
were combined with aggregated STI clinic consultation data in these cities from
the national STI surveillance database (N=113 536). Using negative binomial
regression analyses (adjusted for age and gender), we compared STI consultation
and positivity rates between ethnic groups and cities. RESULTS: Compared with
ethnic Dutch (consultation rate: 40.3/1000 person-years), EM from Eastern Europe,
Sub-Sahara Africa, Suriname, the Netherlands Antilles/Aruba and Latin America had
higher consultation rates (range relative risk (RR): 1.27-2.26), whereas EM from
Turkey, North Africa, Asia and Western countries had lower consultation rates
(range RR: 0.29-0.82). Of the consultations among ethnic Dutch, 12.2% was STI
positive. Positivity rates were higher among all EM groups (range RR: 1.14-1.81).
Consultation rates were highest in Amsterdam and lowest in Utrecht independent of
ethnic background (range RR Amsterdam vs Utrecht: 4.30-10.30). Positivity rates
differed less between cities. CONCLUSIONS: There were substantial differences in
STI clinic use between ethnic groups and cities in the Netherlands. Although
higher positivity rates among EM suggest that these high-risk individuals reach
STI clinics, it remains unknown whether their reach is optimal. Special attention
should be given to EM with comparatively low consultation rates.
PMID- 27606683
TI - Harnessing the Microbiome to Prevent Fungal Infections: Lessons from Amphibians.
PMID- 27606685
TI - Reuse of Organomineral Substrate Waste from Hydroponic Systems as Fertilizer in
Open-Field Production Increases Yields, Flavonoid Glycosides, and Caffeic Acid
Derivatives of Red Oak Leaf Lettuce (Lactuca sativa L.) Much More than Synthetic
Fertilizer.
AB - Effects of organic waste from a hydroponic system added with minerals
(organomineral fertilizer) and synthetic fertilizer on major polyphenols of red
oak leaf lettuce using HPLC-DAD-ESI-MS(3) were investigated. Interestingly,
contents of the main flavonoid glycosides and caffeic acid derivatives of lettuce
treated with organomineral fertilizer were equal to those synthesized without
soil additives. This was found although soil nutrient concentrations, including
that of nitrogen, were much lower without additives. However, lettuce treated
with synthetic fertilizer showed a significant decrease in contents of caffeic
acid derivatives and flavonoid glycosides up to 78.3 and 54.2%, respectively. It
is assumed that a negative effect of a high yield on polyphenols as described in
the growth-differentiation balance hypothesis can be counteracted by (i) a higher
concentration of Mg or (ii) optimal physical properties of the soil structure.
Finally, the organomineral substrate waste reused as fertilizer and soil improver
resulted in the highest yield (+78.7%), a total fertilizer saving of 322 kg ha(
1) and waste reduction in greenhouses.
PMID- 27606684
TI - The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional
Roles.
AB - A major goal of systems neuroscience is to decipher the structure-function
relationship in neural networks. Here we study network functionality in light of
the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be
connected the more common neighbors it shares. Focusing on the fully-mapped
neural network of C. elegans worms, we establish that the CNR is an emerging
property in this connectome. Moreover, sets of common neighbors form homogenous
structures that appear in defined layers of the network. Simulations of signal
propagation reveal their potential functional roles: signal amplification and
short-term memory at the sensory/inter-neuron layer, and synchronized activity at
the motoneuron layer supporting coordinated movement. A coarse-grained view of
the neural network based on homogenous connected sets alone reveals a simple
modular network architecture that is intuitive to understand. These findings
provide a novel framework for analyzing larger, more complex, connectomes once
these become available.
PMID- 27606686
TI - Short-Term Pretreatment of Sub-Inhibitory Concentrations of Gentamycin Inhibits
the Swarming Motility of Escherichia Coli by Down-Regulating the Succinate
Dehydrogenase Gene.
AB - BACKGROUND/AIMS: Motility is a feature of many pathogens that contributes to the
migration and dispersion of the infectious agent. Whether gentamycin has a post
antibiotic effect (PAE) on the swarming and swimming motility of Escherichia coli
(E. coli) remains unknown. In this study, we aimed to examine whether short-term
pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E.
coli and the mechanisms involved therein. METHODS: After exposure to sub
inhibitory concentrations (0.8 MUg/ml) of gentamicin, the swarming and swimming
motility of E. coli was tested in semi-solid media. Real-time PCR was used to
detect the gene expression of succinate dehydrogenase (SDH). The production of
SDH and fumarate by E. coli pretreated with or without gentamycin was measured.
Fumarate was added to swarming agar to determine whether fumarate could restore
the swarming motility of E. coli. RESULTS: After pretreatment of E. coli with sub
inhibitory concentrations of gentamycin, swarming motility was repressed in the
absence of growth inhibition. The expression of all four subunits of SDH was down
regulated, and the intracellular concentration of SDH and fumarate, produced by
E. coli, were both decreased. Supplementary fumarate could restore the swarming
motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic
acid) could strongly repress the swarming motility. CONCLUSION: Sub-inhibitory
concentrations of gentamycin inhibits the swarming motility of E. coli. This
effect is mediated by a reduction in cellular fumarate caused by down-regulation
of SDH. Gentamycin may be advantageous for treatment of E. coli infections.
PMID- 27606687
TI - Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes
in the Acute Respiratory Distress Syndrome.
AB - Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by
heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a
broad gene family induced by Type I interferons, often as a response to viral
infections, which evokes extensive immunomodulation. We tested the hypothesis
that over- or under-expression of immunomodulatory ISG by neutrophils is
associated with worse clinical outcomes in patients with ARDS. Genome-wide
transcriptional profiles of circulating neutrophils isolated from patients with
sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to
characterize ISG expression. Hierarchical clustering of expression identified 3
distinct subject groups with Low, Mid and High ISG expression. ISG accounting for
the greatest variability in expression were identified (MX1, IFIT1, and ISG15)
and used to analyze a prospective cohort at the Colorado ARDS Network site. One
hundred twenty ARDS patients from four urban hospitals were enrolled within 72
hours of initiation of mechanical ventilation. Circulating neutrophils were
isolated from patients and expression of ISG determined by PCR. Samples were
stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82)
or Low (n = 17) ISG expression. Clinical outcomes were compared between patients
with High or Low ISG expression to those with Mid-range expression. At
enrollment, there were no differences in age, gender, co-existing medical
conditions, or type of physiologic injury between cohorts. After adjusting for
age, race, gender and BMI, patients with either High or Low ISG expression had
significantly worse clinical outcomes than those in the Mid for number of 28-day
ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day
mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These
findings suggest extremes of ISG expression by circulating neutrophils from ARDS
patients recovered early in the syndrome are associated with poorer clinical
outcomes.
PMID- 27606691
TI - Revealing the nature of excitons in liquid exfoliated monolayer tungsten
disulphide.
AB - Transition metal dichalcogenides (TMD) hold promise for applications in novel
optoelectronic devices. There is therefore a need for materials that can be
obtained in large quantities and with well understood optical properties. In this
report, we present thorough photoluminescence (PL) investigations of monolayer
tungsten disulphide obtained via liquid phase exfoliation. As shown by microscopy
studies, the exfoliated nanosheets have dimensions of tens of nanometers and
thickness of 2.5 monolayers on average. The monolayer content is about 20%. Our
studies show that at low temperature the PL is dominated by excitons localized on
nanosheet edges. As a consequence, the PL is strongly sensitive to the
environment and exhibits an enhanced splitting in magnetic field. As the
temperature is increased, the excitons are thermally excited out of the defect
states and the dominant transition is that of the negatively charged exciton.
Furthermore, upon excitation with a circularly polarized light, the PL retains a
degree of polarization reaching 50% and inherited from the valley polarized
photoexcited excitons. The studies of PL dynamics reveal that the PL lifetime is
on the order of 10 ps, which is probably limited by non-radiative processes. Our
results underline the potential of liquid exfoliated TMD monolayers in large
scale optoelectronic devices.
PMID- 27606688
TI - Silencing the Olfactory Co-Receptor RferOrco Reduces the Response to Pheromones
in the Red Palm Weevil, Rhynchophorus ferrugineus.
AB - The red palm weevil (RPW, Rhynchophorus ferrugineus), one of the most widespread
of all invasive insect pest species, is a major cause of severe damage to
economically important palm trees. RPW exhibits behaviors very similar to those
of its sympatric species, the Asian palm weevil (R. vulneratus), which is
restricted geographically to the southern part of Southeast Asia. Although
efficient and sustainable control of these pests remains challenging, olfactory
system disruption has been proposed as a promising approach for controlling palm
weevils. Here, we report the cloning and sequencing of an olfactory co-receptor
(Orco) from R. ferrugineus (RferOrco) and R. vulneratus (RvulOrco) and examine
the effects of RferOrco silencing (RNAi) on odorant detection. RferOrco and
RvulOrco encoding 482 amino acids showing 99.58% identity. The injection of
double-stranded RNA (dsRNA) from RferOrco into R. ferrugineus pupae significantly
reduced RferOrco gene expression and led to the failure of odor-stimulus
detection, as confirmed through olfactometer and electroantennography (EAG)
assays. These results suggest that olfactory-system disruption leading to reduced
pheromone detection holds great potential for RPW pest-control strategies.
PMID- 27606692
TI - (1H-Tetrazol-5-yl)-Allenes: Building Blocks for Tetrazolyl Heterocycles.
AB - (1H-Tetrazol-5-yl)-allenes have been prepared for the first time, and their
reactivity toward aziridines explored. Reaction of a (1-benzyl-1H-tetrazol-5-yl)
phosphonium chloride and acyl chlorides in the presence of triethylamine afforded
the target allenes via Wittig reaction of the in situ generated phosphorus ylide
and ketenes. 1-(1-Benzyl-1H-tetrazol-5-yl)propa-1,2-diene and 3-methyl-, 3-ethyl-
and 3-benzyl derivatives undergo microwave-induced formal [3 + 2] cycloaddition
with cis-N-benzyl-2-benzoyl-3-phenylaziridine, through C-N bond cleavage, to give
selectively tetrasubstituted pyrroles. In contrast, with (1H-tetrazol-5-yl)
allenes bearing bulkier substituents at C-3, such as i-propyl or a tert-butyl, 4
methylenepyrrolidines were obtained exclusively via [3 + 2] cycloaddition of the
in situ generated azomethine ylide. The latter allenes also gave 4
methylenepyrrolidines on reacting with cis-2-benzoyl-N-cyclohexyl-3
phenylaziridine, whereas with the other allenes, pyrroles were obtained as major
products together with the formation of 4-methylenepyrrolidines. All the studied
(1H-tetrazol-5-yl)-allenes reacted with N-benzyl-cis-3-phenylaziridine-2
carboxylate to give the corresponding 4-methylenepyrrolidines exclusively.
PMID- 27606690
TI - Hydrogen-Rich Saline as an Innovative Therapy for Cataract: A Hypothesis.
AB - Cataract is the leading cause of irreversible blindness worldwide. Increasing
evidence indicates that oxidative stress is an important risk factor contributing
to the development of cataract. Moreover, the enhancement of the antioxidant
defense system may be beneficial to prevent or delay the cataractogenesis. The
term oxidative stress has been defined as a disturbance in the equilibrium status
of oxidant/antioxidant systems with progressive accumulation of reactive oxygen
species (ROS) in intact cells. Superfluous ROS can damage proteins, lipids,
polysaccharides, and nucleic acids within ocular tissues that are closely
correlated with cataract formation. Therefore, prevention of oxidative stress
damage by antioxidants might be considered as a viable means of medically
offsetting the progression of this vision-impairing disease. Molecular hydrogen
has recently been verified to have protective and therapeutic value as an
antioxidant through its ability to selectively reduce cytotoxic ROS such as
hydroxyl radical (OH). Hitherto, hydrogen has been used as a therapeutic element
against multiple pathologies in both animal models and human patients. Unlike
most well-known antioxidants, which are unable to successfully target organelles,
hydrogen has advantageous distribution characteristics enabling it to penetrate
biomembranes and diffuse into the cytosol, mitochondria, and nucleus.
Consequently, we speculate that hydrogen might be an effective antioxidant to
protect against lens damage, and it is important to further explore the
biological mechanism underlying its potential therapeutic effects.
PMID- 27606693
TI - Identifying biomarkers to select patients with early breast cancer suitable for
extended adjuvant endocrine therapy.
AB - PURPOSE OF REVIEW: In this review, we summarize recent and current biomarkers and
assays that are being considered in the selection of suitable patients with
estrogen receptor-positive early breast cancer for extended (years 5-10) adjuvant
endocrine therapy (AET). RECENT FINDINGS: Women with estrogen receptor-positive
early-stage breast cancer (65% of cases) continue to have late risk for distant
recurrence extending beyond 5 years from surgery. Recent large trials have
consistently demonstrated improvement for prolonging endocrine therapy. However,
endocrine therapy can cause women bothersome side effects and can negatively
impact quality of life. Determining which patients remain at risk for disease
recurrence and predicting which of these patients would derive the most benefit
from the addition of extended AET are key issues faced by patients and
oncologists today. A number of predictive molecular assays have been developed
and are being considered as tools to be used in guiding the implementation of
adjuvant systemic therapy. SUMMARY: The future holds much promise and as more
information and understanding is acquired, treatment regimens will increasingly
incorporate clinically validated biomarker assays in the decision-making process
that will be of great benefit to these patients. Proving clinical utility,
though, will ultimately decide their implementation.
PMID- 27606689
TI - Resveratrol Specifically Kills Cancer Cells by a Devastating Increase in the Ca2+
Coupling Between the Greatly Tethered Endoplasmic Reticulum and Mitochondria.
AB - BACKGROUND/AIMS: Resveratrol and its derivate piceatannol are known to induce
cancer cell-specific cell death. While multiple mechanisms of actions have been
described including the inhibition of ATP synthase, changes in mitochondrial
membrane potential and ROS levels, the exact mechanisms of cancer specificity of
these polyphenols remain unclear. This paper is designed to reveal the molecular
basis of the cancer-specific initiation of cell death by resveratrol and
piceatannol. METHODS: The two cancer cell lines EA.hy926 and HeLa, and somatic
short-term cultured HUVEC were used. Cell viability and caspase 3/7 activity were
tested. Mitochondrial, cytosolic and endoplasmic reticulum Ca2+ as well as
cytosolic and mitochondrial ATP levels were measured using single cell
fluorescence microscopy and respective genetically-encoded sensors. Mitochondria
ER junctions were analyzed applying super-resolution SIM and ImageJ-based image
analysis. RESULTS: Resveratrol and piceatannol selectively trigger death in
cancer but not somatic cells. Hence, these polyphenols strongly enhanced
mitochondrial Ca2+ uptake in cancer exclusively. Resveratrol and piceatannol
predominantly affect mitochondrial but not cytosolic ATP content that yields in a
reduced SERCA activity. Decreased SERCA activity and the strongly enriched
tethering of the ER and mitochondria in cancer cells result in an enhanced
MCU/Letm1-dependent mitochondrial Ca2+ uptake upon intracellular Ca2+ release
exclusively in cancer cells. Accordingly, resveratrol/piceatannol-induced cancer
cell death could be prevented by siRNA-mediated knock-down of MCU and Letm1.
CONCLUSIONS: Because their greatly enriched ER-mitochondria tethering, cancer
cells are highly susceptible for resveratrol/piceatannol-induced reduction of
SERCA activity to yield mitochondrial Ca2+ overload and subsequent cancer cell
death.
PMID- 27606694
TI - Utility of flow cytometry studies in the management of patients with multiple
myeloma.
AB - PURPOSE OF REVIEW: Although the input of multiparameter flow cytometry (MFC) into
the clinical management of multiple myeloma patients has faced some reluctance,
continuously growing evidence supports the utility of MFC in this disease. RECENT
FINDINGS: MFC immunophenotyping of bone marrow and peripheral blood plasma cells
affords cost-effective assessment of clonality, and provides prognostic
information on the risk of progression in smoldering multiple myeloma, and the
identification of active multiple myeloma patients with dismal outcome (e.g.,
high numbers of circulating tumor cells) or long-term survival despite suboptimal
responses through the characterization of monoclonal gammopathy of undetermined
significance-like phenotypes. Extensive data indicate that minimal residual
disease (MRD) monitoring can be used as biomarker to evaluate treatment efficacy
and act as surrogate for survival. The time has come to address within clinical
trials the exact role of baseline risk factors and MRD monitoring for tailored
therapy in multiple myeloma, which implies systematic usage of highly sensitive
cost-effective, readily available, and standardized MRD techniques such as MFC.
SUMMARY: Next-generation MFC should be considered mandatory in the routine
evaluation of multiple myeloma patients both at diagnosis and after therapy, and
represents an attractive technique to integrate with high-throughput DNA and RNA
seq methods to help in understanding the mechanisms behind dissemination and
chemoresistance of multiple myeloma.
PMID- 27606695
TI - Treatment of brain metastasis: current status and future directions.
AB - PURPOSE OF REVIEW: The purpose of this review is to highlight the most recent
advances in the management of brain metastases. RECENT FINDINGS: Role of local
therapies (surgery and stereotactic radiosurgery), new approaches to minimize
cognitive sequelae following whole-brain radiotherapy and advances in targeted
therapies have been reviewed. SUMMARY: The implications for clinical trials and
daily practice of the increasing use of stereotactic radiosurgery in multiple
brain metastases and upfront targeted agents in asymptomatic brain metastases are
discussed.
PMID- 27606696
TI - Extended adjuvant endocrine therapy in hormone-receptor-positive early breast
cancer.
AB - PURPOSE OF REVIEW: The risk of relapse associated with oestrogen receptor
positive early breast cancer persists for at least 15 years after diagnosis.
Several large clinical trials have examined extended adjuvant endocrine therapy.
RECENT FINDINGS: The MA.17 trial demonstrated improved disease-free survival
(DFS) with use of letrozole for 5 years after some years of tamoxifen and an
overall survival advantage for this approach in women with node-positive
oestrogen receptor-positive cancer at diagnosis. The subsequent adjuvant
tamoxifen - to offer more? and adjuvant tamoxifen: longer against shorter trials
demonstrated a DFS advantage for 10 years of tamoxifen over 5 years. The recently
reported MA.17R trial randomized women who had already completed 5 years of
aromatase inhibitor therapy with or without previous tamoxifen to further 5 years
of letrozole or placebo. DFS was significantly improved in the extended letrozole
group, quality of life was similar but bone fracture rates were higher. The
absolute benefit in terms of reduced distant recurrences in these studies is
modest, and tolerability and compliance challenges remain. SUMMARY: Physicians
and patients now have multiple evidence-based treatment options for women who
complete 5 years of adjuvant endocrine therapy. Extended therapy with either
tamoxifen or letrozole should be considered for all and decision based on
menopausal status, individual risk, tolerance and magnitude of potential benefit.
PMID- 27606697
TI - Extended anti-HER2 therapy in early breast cancer: longer beats shorter?
AB - PURPOSE OF REVIEW: One-year duration of adjuvant trastuzumab is the gold standard
since 2005. During the last decade many attempts have been made to both increase
and reduce the treatment duration. The purpose of this article is to review the
current available evidence regarding alternative anti-HER2 therapy durations in
the (neo)adjuvant treatment of HER2-positive localized breast cancer patients.
RECENT FINDINGS: According to the majority of published data, shorter trastuzumab
schedule has shown a decreased benefit in the overall HER2 population, whereas
extending adjuvant trastuzumab, beyond 1 year, does not improve the outcome and
is associated with increased cardiac toxicity. However, new challenging questions
are raised by the recent results of ExteNet trial, in which sequential
introduction of 1 year neratinib after standard trastumab-based therapy improved
the outcome, especially in the estrogen receptor-positive subset of patients.
SUMMARY: To date the standard duration of adjuvant trastuzumab remains 1 year in
the adjuvant setting. It is likely that ongoing trials will clarify which
patients could benefit from a shorter or a longer treatment. Taking into account
patient's specific risk/benefit ratio and new biomarkers, in future, a
'personalized' treatment duration would be warranted.
PMID- 27606698
TI - Practical implications of integrated glioma classification according to the World
Health Organization classification of tumors of the central nervous system 2016.
AB - PURPOSE OF REVIEW: Morphological features identifiable by light microscopy have
been the basis of brain tumor diagnostics for many decades. The revised WHO
classification of tumors of the central nervous system 2016 combines histological
and molecular features for an integrated classification. This new approach builds
upon advances in brain tumor molecular genetics and has important practical
implications. RECENT FINDINGS: Molecular genetic studies revealed distinct glioma
entities with specific genetic and epigenetic profiles. Evidence has been
accumulated that molecular classification more reliably discriminates glioma
entities and better predicts patient outcome than histological classification.
Major glioma entities can be distinguished by four molecular biomarkers included
in the new WHO classification, namely isocitrate dehydrogenase mutation,
codeletion of chromosome arms 1p and 19q, codon 27 lysine-to-methionine mutation
in H3 histones, and C11orf95-RELA gene fusions. Each is detectable by common
techniques in routinely processed tissue specimens. Their integration into glioma
classification greatly improves diagnostic accuracy but also has practical
implications concerning establishment and quality control of novel techniques,
increased costs and prolonged time to diagnosis. SUMMARY: We summarize the
relevant changes in the revised WHO classification of gliomas, outline the
integrated approach, and discuss its practical implications and potential
challenges.
PMID- 27606699
TI - Randomized controlled trial of prolonged exposure using imaginal exposure vs.
virtual reality exposure in active duty soldiers with deployment-related
posttraumatic stress disorder (PTSD).
AB - OBJECTIVE: Prolonged exposure (PE) is an evidence-based psychotherapy for
posttraumatic stress disorder (PTSD) but there is limited research with active
duty military populations. Virtual reality exposure (VRE) has shown promise but
randomized trials are needed to evaluate efficacy relative to existing standards
of care. This study evaluated the efficacy of VRE and PE for active duty soldiers
with PTSD from deployments to Iraq and Afghanistan. METHOD: Active-duty soldiers
(N = 162) were randomized to 10-sessions of PE, VRE, or a minimal attention
waitlist (WL). Blinded assessors evaluated symptoms at baseline, halfway through
treatment, at posttreatment, and at 3- and 6-month follow-ups using the Clinician
Administered PTSD Scale (CAPS). RESULTS: Intent-to-treat analyses found that both
PE and VRE resulted in significant reductions in PTSD symptoms relative to those
in the WL. The majority of patients demonstrated reliable change in PTSD
symptoms. There was no difference between PE and VRE regarding treatment drop out
before completing 10 sessions (44 and 41% for VRE and PE, respectively). Contrary
to hypotheses, analyses at posttreatment did not show that VRE was superior to
PE. Post hoc analyses found that PE resulted in significantly greater symptom
reductions than VRE at 3- and 6-month follow-up. Both treatments significantly
reduced self-reported stigma. CONCLUSIONS: PE is an efficacious treatment for
active-duty Army soldiers with PTSD from deployments to Iraq or Afghanistan.
Results extend previous evidence supporting the efficacy of PE to active-duty
military personnel and raise important questions for future research on VRE.
(PsycINFO Database Record
PMID- 27606700
TI - Efficacy of a web- and text messaging-based intervention to reduce problem
drinking in adolescents: Results of a cluster-randomized controlled trial.
AB - OBJECTIVE: To test the efficacy of a combined web- and text messaging-based
intervention to reduce problem drinking in young people compared to assessment
only. METHOD: Two-arm, parallel-group, cluster-randomized controlled trial with
assessments at baseline and 6-month follow up. The automated intervention
included online feedback, based on the social norms approach, and individually
tailored text messages addressing social norms, outcome expectations, motivation,
self-efficacy, and planning processes, provided over 3 months. The main outcome
criterion was the prevalence of risky single-occasion drinking (RSOD, defined as
drinking at least 5 standard drinks on a single occasion in men and 4 in women)
in the past 30 days. Irrespective of alcohol consumption, 1,355 students from 80
Swiss vocational and upper secondary school classes, all of whom owned a mobile
phone, were invited to participate in the study. Of these, 1,041 (76.8%) students
participated in the study. RESULTS: Based on intention-to-treat analyses, RSOD
prevalence decreased by 5.9% in the intervention group and increased by 2.6% in
the control group, relative to that of baseline assessment (odds ratio [OR] =
0.62, 95% confidence interval [CI] = 0.44-0.87). No significant group differences
were observed for the following secondary outcomes: RSOD frequency, quantity of
alcohol consumed, estimated peak blood alcohol concentration, and overestimation
of peer drinking norms. CONCLUSIONS: The intervention program reduced RSOD, which
is a major indicator of problem drinking in young people, effectively. (PsycINFO
Database Record
PMID- 27606701
TI - In vitro/in vivo evaluation of gamma-aminobutyric acid-loadedN,N
dimethylacrylamide-based pegylated polymeric nanoparticles for brain delivery to
treat epilepsy.
AB - Objectives of this study were the delivery of gamma aminobutyric acid (GABA) into
the brain by means of developing brain targeted, nanosized, non-toxic and
biocompatible polymeric nanoparticles, and investigating their effectiveness in
epilepsy. For this purpose, GABA conjugated N,N-dimethylacrylamide-based
pegylated nanoparticles were designed and characterised for particle size, zeta
potential, pH, morphology, DSC, XRD, FTIR, GABA quantification and in vitro
release. Formulations showed smaller particle size, cationic zeta potential
characteristic, possible GABA polymeric matrix interaction and prolonged release
pattern. Brain responses were examined using epileptic rats. Both formulations
prepared were found to increase latency of seizure, decrease ending time of
convulsion, duration of severe convulsion and mortality rate significantly
compared with GABA solution. When GABA concentration was measured in Stratum
corsatum, there was no statistical difference between GABA solution and
formulations. All findings suggested enhancement in all phases of seizures
indicating efficient delivery of GABA into the brain via formulations.
PMID- 27606702
TI - Efficient Catalytic Electrode for CO2 Reduction Realized by Physisorbing
Ni(cyclam) Molecules with Hydrophobicity Based on Hansen's Theory.
AB - An electrochemical electrode physisorbed with Ni(cyclam) complex molecules
containing tetraphenylborate ions (BPh4(-)) as counteranions shows catalytic
activity for the reduction reaction of CO2 to CO in an aqueous electrolyte,
superior to that of an electrode physisorbed with conventional [Ni(cyclam)]Cl2
complex molecules. The BPh4(-)-containing Ni(cyclam) is inferred as having high
hydrophobicity based on its Hansen solubility parameter (HSP), with an
interaction sphere excluding HSPs of water in a three-dimensional vector space.
The high hydrophobicity of BPh4(-)-containing Ni(cyclam) molecules inhibits their
dissolution into aqueous electrolyte and retains their immobilization onto the
electrode surface, which we believe to result in the improved catalytic activity
of the electrode physisorbed with them. HSP analysis also provides an optimized
mixing ratio of solvents dissolving BPh4(-)-containing Ni(cyclam) molecules.
PMID- 27606704
TI - [Die Zukunft der Homoopathie].
PMID- 27606703
TI - Novel Bovine Papillomavirus Type Discovered by Rolling-Circle Amplification
Coupled with Next-Generation Sequencing.
AB - Currently, fifteen bovine papillomavirus (BPV) types have been identified and
classified into four genera: Deltapapillomavirus, Epsilonpapillomavirus,
Dyoxipapillomavirus, and Xipapillomavirus. Here, the complete genome sequence of
a new BPV type (BPV 04AC14) recovered from a papillomatous lesion is reported.
The genome is 7,282 bp in length and exhibits the classic genetic organization
and motifs of the members of Papillomaviridae. Maximum likelihood phylogenetic
analyses revealed that BPV 04AC14 clusters with members of the Xipapillomavirus
genus. The nucleotide sequence of the L1 capsid protein of the novel BPV is
closely related to its counterpart, BPV3, with which it shares 79% similarity.
These findings suggest that this virus is a new BPV type of the Xipapillomavirus
genus.
PMID- 27606705
TI - Development of Recombinant Lactococcus lactis Displaying Albumin-Binding Domain
Variants against Shiga Toxin 1 B Subunit.
AB - Infections with shiga toxin-producing bacteria, like enterohemorrhagic
Escherichia coli and Shigella dysenteriae, represent a serious medical problem.
No specific and effective treatment is available for patients with these
infections, creating a need for the development of new therapies. Recombinant
lactic acid bacterium Lactococcus lactis was engineered to bind Shiga toxin by
displaying novel designed albumin binding domains (ABD) against Shiga toxin 1 B
subunit (Stx1B) on their surface. Functional recombinant Stx1B was produced in
Escherichia coli and used as a target for selection of 17 different ABD variants
(named S1B) from the ABD scaffold-derived high-complex combinatorial library in
combination with a five-round ribosome display. Two most promising S1Bs (S1B22
and S1B26) were characterized into more details by ELISA, surface plasmon
resonance and microscale thermophoresis. Addition of S1Bs changed the subcellular
distribution of Stx1B, completely eliminating it from Golgi apparatus most likely
by interfering with its retrograde transport. All ABD variants were successfully
displayed on the surface of L. lactis by fusing to the Usp45 secretion signal and
to the peptidoglycan-binding C terminus of AcmA. Binding of Stx1B by engineered
lactococcal cells was confirmed using flow cytometry and whole cell ELISA. Lactic
acid bacteria prepared in this study are potentially useful for the removal of
Shiga toxin from human intestine.
PMID- 27606706
TI - Effects of Age and Body Mass Index on Thoracolumbar Spine X-Ray for Diagnosing
Osteoporosis in Elderly Women: Tianliao Old People (TOP) Study 07.
AB - PURPOSE: The aim of this study was to determine the effects of diagnostic
discordance with or without a thoracolumbar spine lateral view X-ray in patients
with osteoporosis. METHODS: We randomly enrolled 368 women over 65 years old
(74.3 +/- 6.0 years) from Tianliao Township in 2009 (response rate: 75.7%). A
diagnosis of osteoporosis was confirmed using one of these criteria: (1) a
history of non-traumatic fracture, (2) vertebral fractures based on a
thoracolumbar spine lateral view X-ray, or (3) a bone mineral density T-score <=
2.5 for the total hip, the femoral neck, the lumbar spine, or all 3 sites. The
prevalence of osteoporosis in three groups was compared based on Model I
(criteria 1+2) vs. Model II (criteria 1+3) vs. Model III (criteria 1+2+3). The
role of thoracolumbar X-ray reflected by the diagnostic discordance of
osteoporosis between Models II and III was evaluated. RESULTS: The overall
prevalence of osteoporosis was 78.3% (Model III, age-standardized 78.1%). The
diagnostic discordance was 17.4% in the 368 participants. A logistic regression
model showed that age was negatively associated with diagnostic discordance (odds
ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.98, p < 0.05), but body
mass index was positively associated (OR = 1.07, 95% CI: 1.00-1.15, p < 0.05).
CONCLUSIONS: A thoracolumbar spine lateral view X-ray should be added for women
>= 65 years old or with a body mass index >= 25 kg/m2 to minimize the diagnostic
discordance in osteoporosis, especially in highly endemic regions.
PMID- 27606707
TI - The Social Costs of Ubiquitous Information: Consuming Information on Mobile
Phones Is Associated with Lower Trust.
AB - In an age already saturated with information, the ongoing revolution in mobile
computing has expanded the realm of immediate information access far beyond our
homes and offices. In addition to changing where people can access information,
mobile computing has changed what information people access-from finding specific
directions to a restaurant to exploring nearby businesses when on the go. Does
this ability to instantly gratify our information needs anytime and anywhere have
any bearing on how much we trust those around us-from neighbors to strangers?
Using data from a large nationally representative survey (World Values Survey:
Wave 6), we found that the more people relied on their mobile phones for
information, the less they trusted strangers, neighbors and people from other
religions and nationalities. In contrast, obtaining information through any other
method-including TV, radio, newspapers, and even the Internet more broadly
predicted higher trust in those groups. Mobile information had no bearing on how
much people trusted close others, such as their family. Although causality cannot
be inferred, these findings provide an intriguing first glimpse into the possible
unforeseen costs of convenient information access for the social lubricant of
society-our sense of trust in one another.
PMID- 27606709
TI - Development of replication-deficient adenovirus malaria vaccines.
AB - INTRODUCTION: Malaria remains a major threat to endemic populations and
travelers, including military personnel to these areas. A malaria vaccine is
feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas
covered: This review covers current malaria clinical trials using adenoviruses
and pre-clinical research. Heterologous prime-boost regimens, including
replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are
efficacious. However, efficacy appears to be adversely affected by pre-existing
anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer
human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The
chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials
including infants in malaria-endemic areas. Key antigens have been identified and
are being used alone, in combination, or with protein subunit vaccines. Gorilla
adenoviruses carrying malaria antigens are also currently being evaluated in
preclinical models. These replacement adenovirus vectors will be successfully
used to develop vaccines against malaria, as well as other infectious diseases.
Expert commentary: Simplified prime-boost single shot regimens, dry-coated live
vector vaccines or silicon microneedle arrays could be developed for malaria or
other vaccines. Replacement vectors with similar or superior immunogenicity have
rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria
as well as other diseases, notably Ebola.
PMID- 27606708
TI - Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia
tsutsugamushi Infection.
AB - T cells are known to contribute to immune protection against scrub typhus, a
potentially fatal infection caused by the obligate intracellular bacterium
Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to
protection and pathogenesis during O. tsutsugamushi infection is still unknown.
Using our recently developed BALB/c mouse model that is based on footpad
inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T
cells infiltrate spleen and lung during the third week of infection. Depletion of
CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth
and mortality. Adoptive transfer of CD8+ T cells from infected animals protected
naive BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6
mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+
T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+
T cells at 84 days post infection caused reactivation of bacterial growth. In
CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication
was uncontrolled, and all mice succumbed to the infection, despite higher serum
IFN-gamma levels and stronger macrophage responses in liver and lung. Moreover,
we show that CD8+ T cells but not NKT cells were required for hepatocyte injury:
elevated concentrations of serum alanine aminotransferase and infection-induced
subcapsular necrotic liver lesions surrounded by macrophages were found in
C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice.
In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T
cells. In summary, our results demonstrate that CD8+ T cells restrict growth of
O. tsutsugamushi during acute and persistent infection, and are required to
protect from lethal infections in BALB/c and C57BL/6 mice. However, they also
elicit specific pathologic tissue lesions in liver and lung.
PMID- 27606711
TI - Pelvic fracture of the sacroiliac joint region in a child - a case study and
literature review.
AB - The aim of the paper is to present the case of a 3-year-old boy with an unaligned
fracture of the sacroiliac joint region to propose a minimally invasive method of
fracture fixation without using metal implants and to review the literature
addressing this injury, which is uncommon in children. The patient was hit by a
car; he suffered a fracture of the iliac ala with a complete traumatic damage to
the L4-L5 nerve roots. The fracture was fixated by osteosuture and normal bone
fusion was achieved. The follow-up period was 4 years. The boy manifested
persistent flaccid paresis of the right foot and symptoms of a neurogenic
bladder. Late radiological follow-up indicated disturbances of pelvic bone
development and shortening of the lower extremity at the side of the injury.
PMID- 27606710
TI - Exposing therapists to trauma-focused treatment in psychosis: effects on
credibility, expected burden, and harm expectancies.
AB - BACKGROUND: Despite robust empirical support for the efficacy of trauma-focused
treatments, the dissemination proves difficult, especially in relation to
patients with comorbid psychosis. Many therapists endorse negative beliefs about
the credibility, burden, and harm of such treatment. OBJECTIVE: This feasibility
study explores the impact of specialized training on therapists' beliefs about
trauma-focused treatment within a randomized controlled trial. METHOD: Therapist
rated (n=16) credibility, expected burden, and harm expectancies of trauma
focused treatment were assessed at baseline, post-theoretical training, post
technical training, post-supervised practical training, and at 2-year follow-up.
Credibility and burden beliefs of therapists concerning the treatment of every
specific patient in the trial were also assessed. RESULTS: Over time, therapist
rated credibility of trauma-focused treatment showed a significant increase,
whereas therapists' expected burden and harm expectancies decreased
significantly. In treating posttraumatic stress disorder (PTSD) in patients with
psychotic disorders (n=79), pre-treatment symptom severity was not associated
with therapist-rated credibility or expected burden of that specific treatment.
Treatment outcome had no influence on patient-specific credibility or burden
expectancies of therapists. CONCLUSIONS: These findings support the notion that
specialized training, including practical training with supervision, has long
term positive effects on therapists' credibility, burden, and harm beliefs
concerning trauma-focused treatment.
PMID- 27606712
TI - Activity-related energy expenditure during lower limb cast immobilization in
children.
AB - : Physical inactivity, which may result from immobilization, is recognized as a
risk factor for the development of obesity. We aimed to quantify the decrease in
activity-related energy expenditure (AEE) because of lower limb cast
immobilization. We carried out a longitudinal matched case-control study: 34
adolescents with a first episode of lower limb fracture and 34 healthy cases.
Physical activity was assessed during cast immobilization by an accelerometer
from which we calculated the decrease in AEE. AEE in adolescents with lower limb
fractures was estimated to be 16.0% lower than healthy controls. When converted
into kcal per mean participants' weight, the difference in AEE amounted to 125
kcal/day, which corresponds to 5.2 h of slow walking. A significant reduction of
AEE in adolescents with lower limb fractures may lead to a significantly positive
energy balance as there is usually no compensatory reduction of energy intake. An
increase of walking seems unrealistic in this situation and patients should be
advised at the emergency unit to reduce their energy intake during the
immobilization period. LEVEL OF EVIDENCE: Level III, prospective case-control
study.
PMID- 27606713
TI - Clinical experiences of focal periphyseal edema zones in adolescent knees: case
reports.
AB - Focal periphyseal edema (FOPE) zones were first described in 2011. The aim of
this report was to investigate the clinical course of patients with FOPE zones.
Three adolescent patients with a FOPE zone in the knee were treated and observed
for a maximum of 2 years. No symptoms or leg-length discrepancy developed at the
final follow-up after conservative therapies. This is the first report on the
follow-up of FOPE zones with a maximum of 2 years. The results suggest that
observation of FOPE zones may be sufficient without invasive examinations and
treatment.
PMID- 27606715
TI - Low temperature dry etching of chromium towards control at sub-5 nm dimensions.
AB - Patterned chromium and its compounds are crucial materials for nanoscale
patterning and chromium based devices. Here we investigate how temperature can be
used to control chromium etching using chlorine/oxygen gas mixtures.
Oxygen/chlorine ratios between 0% and 100% and temperatures between -100 degrees
C and +40 degrees C are studied. Spectroscopic ellipsometry is used to precisely
measure rates, chlorination, and the thickness dependence of n and k. Working in
the extremes of oxygen content (very high or very low) and lower temperatures, we
find rates can be controlled to nanometers per minute. Activation energies are
measured and show that etch mechanisms are both temperature and oxygen level
dependent. Furthermore, we find that etching temperature can manipulate the
surface chemistry. One surprising consequence is that at low oxygen levels,
Etching rates increase with decreasing temperature. Preliminary feature-profile
studies show the extremes of temperature and oxygen provide advantages over
commonly used room temperature processing conditions. One example is with higher
ion energies at -100 degrees C, where etching products deposit.
PMID- 27606714
TI - Desorption Dynamics of Rb2 Molecules Off the Surface of Helium Nanodroplets.
AB - The desorption dynamics of rubidium dimers (Rb2) off the surface of helium
nanodroplets induced by laser excitation is studied by employing both nanosecond
and femtosecond ion imaging spectroscopy. Similarly to alkali metal atoms, we
find that the Rb2 desorption process resembles the dissociation of a diatomic
molecule. However, both angular and energy distributions of detected Rb2+ ions
appear to be most crucially determined by the Rb2 intramolecular degrees of
freedom rather than by those of the Rb2HeN complex. The pump-probe dynamics of
Rb2+ is found to be slower than that of Rb+, pointing at a weaker effective guest
host repulsion for excited molecules than for single atoms.
PMID- 27606716
TI - Carotid ultrasound in the cardiovascular risk stratification of patients with
ankylosing spondylitis: results of a population-based study.
AB - OBJECTIVES: To determine if the use of carotid ultrasonography (US) may improve
the cardiovascular (CV) risk stratification in patients with ankylosing
spondylitis (AS). METHODS: A set of 127 consecutive patients without history of
CV events, diabetes mellitus or chronic kidney disease that fulfilled definitions
for AS according to the 1984 modified New York criteria were recruited to assess
carotid intima-media thickness and presence of plaques. CV risk was calculated
according to the systematic coronary risk evaluation (SCORE), the Framingham Risk
Score (FRS) and the Reynolds Risk Score (RRS). RESULTS: Men outnumbered women
(61.4%). The mean+/-SD age at the time of the study was 44.5+/-11.6 years. The
median (interquartile range-IQR) disease duration was 13 (7-22) years. The median
(IQR) BASDAI at the time of the study was 3.65 (1.7- 4.9). HLA-B-27 was positive
in 77.2%, and syndesmophytes were present in 38.9%. Carotid plaques were found in
43 (33.9%). Regardless of the algorithm used for CV risk stratification, more
than 50% of the patients classified as having moderate CV risk had carotid
plaques. Moreover, 20.8%, 24.6% and 53.3% of AS that fulfilled the category of
low CV risk according to the total cholesterol (TC)-SCORE, FRS and RRS,
respectively had carotid plaques. A model that included patients with a chart TC
SCORE >=5% or TC-SCORE >=1% <5% plus carotid plaques or TC-SCORE <1% and CRP >3
mg/L at diagnosis plus syndesmophytes and carotid plaques or TC-SCORE <1% and CRP
>3 mg/L at diagnosis plus extraarticular manifestations plus carotid plaques
yielded the highest sensitivity (93.0%) for high/very high CV risk in these
patients. The presence of syndesmophytes was associated with increased risk of
carotid plaques in AS that fulfilled definitions for low CV risk according to the
TC-SCORE (OR 8.75 [95% CI 2.11-36.40]; p=0.002). CONCLUSIONS: Our results support
the use of carotid US in the assessment of CV risk in patients with AS.
PMID- 27606717
TI - Optimization and Structure-Activity Relationships of Phosphinic Pseudotripeptide
Inhibitors of Aminopeptidases That Generate Antigenic Peptides.
AB - The oxytocinase subfamily of M1 aminopeptidases, consisting of ER aminopeptidase
1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase
(IRAP), plays critical roles in the generation of antigenic peptides and
indirectly regulates human adaptive immune responses. We have previously
demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors
of this group of enzymes. In this study, we used synthetic methodologies able to
furnish a series of stereochemically defined phosphinic pseudotripeptides and
demonstrate that side chains at P1' and P2' positions are critical determinants
in driving potency and selectivity. We identified low nanomolar inhibitors of
ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude,
respectively. Cellular analysis demonstrated that one of the compounds that is a
selective IRAP inhibitor can reduce IRAP-dependent but not ERAP1-dependent cross
presentation by dendritic cells with nanomolar efficacy. Our results encourage
further preclinical development of phosphinic pseudotripeptides as regulators of
adaptive immune responses.
PMID- 27606718
TI - Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo
Microenvironment of Lung Cancer Metastasis.
AB - Metastasis is a complex pathophysiological process. As the main cause of cancer
mortality in humans it represents a serious challenge to both basic researchers
and clinicians. Here we report the design and construction of a multi-organ
microfluidic chip that closely mimics the in vivo microenvironment of lung cancer
metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three
downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and
two thin PDMS microporous membranes bonded to form three parallel microchannels.
Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and
fibroblast cells were grown separated by the biomembrane in upstream "lung",
while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to
mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in
this system, lung cancer cells formed a "tumor mass", showed epithelial
mesenchymal transition (with altered expression of E-cadherin, N-cadherin,
Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes
overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell
metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage
of osteocytes after cancer cell metastasis to the bone, and hepatocytes
overexpressed AFP protein indicates damage to hepatocytes after cancer cell
metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis
in a nude mice model validated the performance of metastasis in the organs-on
chip system. This system provides a useful tool to mimic the in vivo
microenvironment of cancer metastasis and to investigate cell-cell interactions
during metastasis.
PMID- 27606719
TI - Adolescent Substance Use in the Context of the Family: A Qualitative Study of
Young People's Views on Parent-Child Attachments, Parenting Style and Parental
Substance Use.
AB - BACKGROUND: Adolescent substance use can place youth at risk of a range of poor
outcomes. Few studies have attempted to explore in-depth young people's
perceptions of how familial processes and dynamics influence adolescent substance
use. OBJECTIVES: This article aimed to explore risk and protective factors for
youth substance use within the context of the family with a view to informing
family based interventions. METHODS: Nine focus groups supplemented with
participatory techniques were facilitated with a purposive sample of sixty-two
young people (age 13-17 years) from post-primary schools across Northern Ireland.
The data were transcribed verbatim and analyzed using thematic analysis. RESULTS:
Three themes emerged from the data: (1) parent-child attachments, (2) parenting
style, and (3) parental and sibling substance misuse. Parent-child attachment was
identified as an important factor in protecting adolescents from substance use in
addition to effective parenting particularly an authoritative style supplemented
with parental monitoring and strong parent-child communication to encourage child
disclosure. Family substance use was considered to impact on children's substance
use if exposed at an early age and the harms associated with parental substance
misuse were discussed in detail. Both parent and child gender differences were
cross-cutting themes. CONCLUSION: Parenting programmes (tailored to mothers and
fathers) may benefit young people via components on authoritative styles,
parental monitoring, communication, nurturing attachments and parent-child
conflict. Youth living with more complex issues, e.g., parental substance misuse,
may benefit from programmes delivered beyond the family environment, e.g., school
based settings.
PMID- 27606720
TI - The effects of increasing semantic-associate list length on the Deese-Roediger
McDermott false recognition memory: Dual false-memory process in retrieval from
sub- and supraspan lists.
AB - In this study, the number of semantic associates in Deese-Roediger-McDermott
(DRM) lists was varied from 4 to 14 in a modified Sternberg paradigm. The false
alarm (FA) and correct rejection (CR) reaction time (RT)/memory-set size (MSS)
functions of critical lures showed a cross-over interaction at approximately MSS
7, suggesting a reversal of the relative dominance between these two responses to
the critical lure at this point and also indicating the location of the boundary
between the sub- and supraspan MSS. For the subspan lists, FA to critical lures
was slower than CR, suggesting a slow, strategic mechanism driving the false
memory. Conversely, for the supraspan lists, critical lure FA was faster than its
CR, suggesting a spontaneous mechanism driving the false memory. Results of two
experiments showed that an automatic, fast, and a slow, controlled process could
be error-prone or error-corrective, depending on the length of the DRM memory
list. Thus there is a dual retrieval process in false memory as in true memory.
The findings can be explained by both the activation/monitoring and the fuzzy
trace theories.
PMID- 27606721
TI - Differential receptor dependencies: expression and significance of muscarinic M1
receptors in the biology of prostate cancer.
AB - Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown
its growth-promoting role in prostate cancer. Additional studies report the
proliferative effect of the cholinergic agonist carbachol on prostate cancer by
its agonistic action on CHRM3. This study shows that the type 1 acetylcholine
muscarinic receptor (CHRM1) contributes toward the proliferation and growth of
prostate cancer. We used growth and cytotoxic assays, the prostate cancer
microarray database and CHRM downstream pathways' homology of CHRM subtypes to
uncover multiple signals leading to the growth of prostate cancer. Growth assays
showed that pilocarpine stimulates the proliferation of prostate cancer.
Moreover, it shows that carbachol exerts an additional agonistic action on
nicotinic cholinergic receptor of prostate cancer cells that can be blocked by
tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and
dicyclomine, a considerable inhibition of proliferation of prostate cancer cell
lines was observed in dose ranging from 15-60 ug/ml of dicyclomine. The
microarray database of prostate cancer shows a dominant expression of CHRM1 in
prostate cancer compared with other cholinergic subtypes. The bioinformatics of
prostate cancer and CHRM pathways show that the downstream signalling include
PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that
antagonism of CHRM1 may be a potential therapeutic target against prostate
cancer.
PMID- 27606722
TI - Moyamoya disease and systemic sclerosis (MoSys syndrome): a combination of two
rare entities.
PMID- 27606723
TI - Laparoscopic Heller Myotomy and Dor Fundoplication for Esophageal Achalasia:
Technique and Perioperative Management.
AB - Surgical correction of achalasia using laparoscopic Heller myotomy with Dor
fundoplication is argued to be the gold standard treatment for patients with
achalasia. The goal of this technical report is to illustrate our preferred
approach to patients with achalasia and to provide the reader with a detailed
description of our operative technique, its rationale, and our pre and
postoperative management.
PMID- 27606772
TI - Atypical Ductal Hyperplasia: What Is the Current Risk for Developing Breast
Cancer?
PMID- 27606774
TI - Extended Submuscular Blepharoplasty With Orbitomalar Ligament Release and Orbital
Fat Repositioning.
PMID- 27606773
TI - Prevalence and Incidence of Diagnosed Chronic Rhinosinusitis in Alberta, Canada.
AB - Importance: Reported prevalence rates of chronic rhinosinusitis (CRS) range from
1% to 12% worldwide. To facilitate appropriate health service delivery and
resource allocation, it is important to improve the estimated burden of CRS to
the health care system. Objectives: To assess the prevalence and incidence of
diagnosed CRS in Alberta, Canada, from the perspective of the health care system
and to evaluate the 10-year temporal trend and geographic variation of diagnosed
CRS. Design, Setting, and Participants: From provincial-wide physicians' claim
data, a CRS cohort was identified using a validated case definition. The
population at the midpoint (2008-2009) of the study period (2 925 930) was used
as the reference. The crude as well as age- and sex-standardized incidence and
prevalence rates were calculated. The age-specific incidence and prevalence by
sex were also assessed in each study year. Small-area variation analysis was
conducted using extremal quotient, weighted coefficient of variation, chi2
statistic, systematic component of variation, and empirical Bayes variance
estimate. Results: Of the 2 925 930 individuals in the study at midpoint (2008
2009), 1 451 261 (49.6%) were women, and the mean (SD) age was 45 (17) years.
From fiscal year 2004-2005 to fiscal year 2013-2014, the mean age- and sex
standardized incidence of diagnosed CRS was 2.5 (range, 2.3-2.7) per 1000
population. The estimated prevalence based on age-specific incidence varied
between 18.8 (95% CI, 18.7-18.9) and 23.3 (95% CI, 23.1-23.5) per 1000 population
during 2004-2005 to 2013-2014, and no obvious growing trend was found. There was
high geographic variation in the diagnosed incidence and prevalence of CRS (mean
systematic component of variation, 19.4 and 12.3, respectively). Conclusions and
Relevance: Although the incidence and prevalence rates of diagnosed CRS were
lower compared with earlier published estimates obtained from population-based
survey analysis, outcomes from this study may more accurately reflect the disease
burden of CRS to the health care system. Given that the prevalence of CRS within
a single province is expected to be uniformly distributed, the large geographic
variation in diagnosed CRS indicates a potential gap in quality of care and
justifies further investigation into the reasons for the variation.
PMID- 27606775
TI - Citrobacter rodentium mouse model of bacterial infection.
AB - Infection of mice with Citrobacter rodentium is a robust model to study bacterial
pathogenesis, mucosal immunology, the health benefits of probiotics and the role
of the microbiota during infection. C. rodentium was first isolated by Barthold
from an outbreak of mouse diarrhea in Yale University in 1972 and was
'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has
proliferated, and it is now the gold standard for studying virulence of the
closely related human pathogens enteropathogenic and enterohemorrhagic
Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed
protocol for various applications of the model, including bacterial growth, site
directed mutagenesis, mouse inoculation (from cultured cells and after
cohabitation), monitoring of bacterial colonization, tissue extraction and
analysis, immune responses, probiotic treatment and microbiota analysis. The main
protocol, from mouse infection to clearance and analysis of tissues and host
responses, takes ~5 weeks to complete.
PMID- 27606776
TI - Surgical extraction of human dorsal root ganglia from organ donors and
preparation of primary sensory neuron cultures.
AB - Primary cultures of rodent sensory neurons are widely used to investigate the
cellular and molecular mechanisms involved in pain, itch, nerve injury and
regeneration. However, translation of these preclinical findings may be greatly
improved by direct validation in human tissues. We have developed an approach to
extract and culture human sensory neurons in collaboration with a local organ
procurement organization (OPO). Here we describe the surgical procedure for
extraction of human dorsal root ganglia (hDRG) and the necessary modifications to
existing culture techniques to prepare viable adult human sensory neurons for
functional studies. Dissociated sensory neurons can be maintained in culture for
>10 d, and they are amenable to electrophysiological recording, calcium imaging
and viral gene transfer. The entire process of extraction and culturing can be
completed in <7 h, and it can be performed by trained graduate students. This
approach can be applied at any institution with access to organ donors consenting
to tissue donation for research, and is an invaluable resource for improving
translational research.
PMID- 27606777
TI - Analyzing and interpreting genome data at the network level with ConsensusPathDB.
AB - ConsensusPathDB consists of a comprehensive collection of human (as well as mouse
and yeast) molecular interaction data integrated from 32 different public
repositories and a web interface featuring a set of computational methods and
visualization tools to explore these data. This protocol describes the use of
ConsensusPathDB (http://consensuspathdb.org) with respect to the functional and
network-based characterization of biomolecules (genes, proteins and metabolites)
that are submitted to the system either as a priority list or together with
associated experimental data such as RNA-seq. The tool reports interaction
network modules, biochemical pathways and functional information that are
significantly enriched by the user's input, applying computational methods for
statistical over-representation, enrichment and graph analysis. The results of
this protocol can be observed within a few minutes, even with genome-wide data.
The resulting network associations can be used to interpret high-throughput data
mechanistically, to characterize and prioritize biomarkers, to integrate
different omics levels, to design follow-up functional assay experiments and to
generate topology for kinetic models at different scales.
PMID- 27606778
TI - Pregnancy Outcomes in Women with Preeclampsia Superimposed on Chronic
Hypertension with and without Severe Features.
AB - Objective The American Congress of Obstetricians and Gynecologists (ACOG) task
force on hypertension in pregnancy introduced a new definition of superimposed
preeclampsia (SIP) adding severe features (SF) as new criteria to define severe
disease. They also recommended that those with SIP be delivered >= 37 weeks,
whereas those with SF be delivered <= 34 weeks. Our aim was to investigate the
validity of this new definition by comparing adverse pregnancy outcomes in SIP
with (SIP-SF) and without SF (SIP). Study Design Women with chronic hypertension
(CHTN) enrolled in a multicenter trial were studied. SIP was reclassified
according to the new definition to SIP and SIP-SF (persistent systolic blood
pressure [BP] > 160 or diastolic BP > 110, platelets < 100 K, liver function
tests > 70, creatinine > 1.1, or persistent central nervous system/abdominal
symptoms). Composite adverse outcomes including rates of indicated preterm birth,
abruptio placentae, postpartum hemorrhage, and maternal death were compared by
chi-square. Adjustment was done with a multivariate logistic-regression analysis
and all statistical tests were two-sided. Results A total of 216 women (28%) out
of 774 with CHTN developed SIP, 87 (11%) had SIP-SF, and 129 (17%) didn't have
SF. Baseline characteristics including maternal age, baseline BP, and assignment
to low-dose aspirin were similar between groups. Using univariate analysis, the
composite adverse outcome was higher among the SIP-SF group (p = 0.04), as well
as indicated preterm birth (p = 0.02), cesarean section (p = 0.02), and SGA (p =
0.02). After adjustment, composite adverse outcomes were not significantly
different between groups. The rate of SGA, however, was higher among SIP-SF
(adjusted odds ratio: 3.12, p = 0.02). Conclusion The rate of SIP-SF in this
study was 11% of all women with CHTN. Surprisingly, pregnancy outcomes were not
significantly different in those with and without SF. We suggest a prospective
observational study to determine the optimal timing for delivery in those with
SIP using new ACOG diagnostic criteria.
PMID- 27606780
TI - Time for a Change.
PMID- 27606779
TI - Recurrence of Preterm Delivery in Women with a Family History of Preterm
Delivery.
AB - Objective This study aims to evaluate the role of a family history of preterm
delivery on the risk of preterm delivery in the next generation. Study Design A
retrospective population-based study was conducted. Perinatal information was
gathered from 2,303 familial triads, composed of mothers (F1), daughters (F2),
and children (F3). All births occurred in the same regional medical center
between the years 1991 and 2013. Statistical analysis using logistic regression
was performed to define the risk of F2 delivering a preterm baby (F3) if she was
born preterm herself, and then to define the risk of F2 delivering preterm if her
mother (F1) gave birth preterm during any of her birthing events. Results The
risk for preterm delivery of the F2 parturient was 34% greater if their mother
(F1) at any of her births had delivered preterm, controlling for parity, maternal
age at delivery, and preeclampsia (adjusted odds ratio: 1.34, 95% confidence
interval: -1.01 to 1.77; p = 0.042). Conclusion The family history of preterm
delivery is an independent risk factor for preterm delivery. The family history
includes the mother as well as one of the mother's sisters (F2 generation) being
born preterm.
PMID- 27606781
TI - Poly-victimization and resilience portfolios: Trends in violence research that
can enhance the understanding and prevention of elder abuse.
AB - This literature review assesses the current state of knowledge about elder abuse
and mistreatment, focusing on the lack of incorporation of all forms of elder
victimization and the benefits of a poly-victimization framework. This review
also includes existing knowledge on risk factors and calls for a greater focus on
protective factors and a greater inclusion on family and community factors.
Future research, prevention, and intervention would benefit from considering the
true burden of elder victimization and a greater implementation of strengths
based approaches to programs.
PMID- 27606782
TI - On-Farm Diversity and Market Participation Are Positively Associated with Dietary
Diversity of Rural Mothers in Southern Benin, West Africa.
AB - OBJECTIVE: The objective of this study is to test the extent to which, under
different opportunities for market participation, the diversity of plant species
rural households grow or collect (on-farm diversity), and the variety of foods
mothers purchase (market diversity) are associated with their dietary diversity.
METHODS: Rural households from three districts in southern Benin were interviewed
during dry (n = 472) and wet (n = 482) seasons between 2011 and 2012. Villages
within districts and their households were selected randomly according to market
accessibility, with a mother selected from each household. Information on on-farm
diversity was collected using a semi-structured questionnaire. Market diversity
was obtained through a 7-day food frequency questionnaire that elicited if foods
were purchased. Dietary diversity was derived from a quantitative 24-hour food
recall. A system of three simultaneous equations via a Generalized Methods of
Moments was estimated to address potential endogeneity between dietary diversity
and on-farm diversity and market diversity. RESULTS: Results show rich on-farm
diversity with more than 65 different edible plant species grown or collected by
households. More than 70% of foods consumed by mothers were purchased in 55
market places. More than 50% of mothers met minimum dietary diversity with at
least 5 food groups consumed. Diagnostic tests indicated the existence of
endogeneity. Econometric results showed that on-farm and market diversities were
positively associated with mothers' dietary diversity (p < 0.05) once market
opportunities, seasonality and other socioeconomic factors were controlled for.
CONCLUSION: Results provide evidence of a positive relationship between on-farm
diversity and dietary diversity among participant mothers. They demonstrate the
important contribution of market diversity to their dietary diversity. Links
among these three facets of diversity suggest that production for self
consumption and food purchases complement rather than replace each other in their
contribution to dietary diversity and thus dietary quality.
PMID- 27606783
TI - A rare case of large intracoronary thrombosis in advanced breast cancer patient
treated with epirubicin and cisplatin.
AB - : Cancer is associated with a prothrombotic or hypercoagulable state.
Intracoronary thrombosis is a rare and potentially life-threatening complication
in cancer patients. We describe a rare case of large nonocclusive intracoronary
thrombosis successfully treated by means of medical therapy.
PMID- 27606784
TI - Hypertension, hypertrophy, and reperfusion injury.
AB - The heart of patients with hypertension and cardiac hypertrophy is more
vulnerable to ischemia-reperfusion injury (IRI). Here we discuss the main
mechanisms of IRI and possible targets for cardioprotection. In particular, we
consider the viewpoint that hypertension and cardiac hypertrophy may act
synergistically in increasing the predisposition to cardiovascular accidents and
in worsening IRI. There is no doubt that hypertrophic hearts may be redirected to
be less vulnerable to IRI. Some experimental evidences suggest that
antihypertensive drugs may have beneficial effects, some of which are not
directly related to hypertension-lowering effect. However, more thorough
experimental and clinical studies are necessary to understand the mechanisms and
to maximize the beneficial effects of reperfusion after a heart attack in the
presence of comorbidities, such as hypertension and cardiac hypertrophy.
PMID- 27606786
TI - Multimodality imaging of pericardial diseases.
PMID- 27606785
TI - Clinical and echocardiographic predictors of long-term outcome of a large cohort
of patients with bicuspid aortic valve.
AB - BACKGROUND AND OBJECTIVES: Bicuspid aortic valve (BAV) disease is the most common
congenital cardiac malformation. The aim of the present article is to determine
clinical and echocardiographic prognostic factors and provide a predictive model
of outcome of a large cohort of patients with BAV. METHODS: We retrospectively
enrolled 337 patients consecutively assessed for echocardiography at our
Cardiology Department from 1993 to 2014. We considered aortic valve replacement,
aortic surgery and cardiovascular death as a clinical combined end-point.
Predictors of outcome were determined by Cox regression. RESULTS: Mean age was
29.2 +/- 19.8 years, median 27.1 years. A total of 38.4% patients presented a
history of hypertension. Mean duration of follow-up was 8.4 +/- 6.1 years, range
0-21 years. A total of 73 patients underwent aortic valve replacement and/or
aortic surgery during follow-up. Age at surgery was 45.2 +/- 15.6 years. Seven
patients died because of cardiovascular causes. At multivariate analysis,
baseline clinical predictors were history of hypertension [hazard ratio (HR)
2.289, 95% confidence interval (CI) 1.350-3.881, P = 0.002], larger ascending
aortic diameter (HR 2.537, 95% CI 1.888-3.410, P < 0.001), moderate-to-severe
aortic regurgitation (HR 2.266, 95% CI 1.402-3.661, P = 0.001) and moderate-to
severe aortic stenosis (HR 2.807, 95% CI 1.476-5.338, P = 0.002). A predictive
model was created by integrating these four independent covariates. It allows the
calculation of calculate a risk score for each patient, which helps better tailor
appropriate treatment in BAV patients. CONCLUSION: At enrolment, history of
hypertension, a wider aortic diameter, moderate-to-severe aortic regurgitation
and aortic stenosis were independently correlated to combined end-point. Long
term follow-up showed low cardiovascular mortality (2.1%) and a high prevalence
of cardiac surgery (21.6%).
PMID- 27606787
TI - Kinetics and Mechanism of CO Exchange in fac-[MBr2(solvent)(CO)3](-) (M = Re,
(99)Tc).
AB - The self-exchange kinetics of CO ligands in the solvated forms of the commonly
used complex [MBr3(CO)3](2-) (M = Re, (99)Tc) were investigated in-depth by (13)C
NMR spectroscopy in organic solvents such as dimethylformamide and methanol. The
two homologues exhibit surprisingly different chemical behavior. In the case of
rhenium, the stable intermediate [NEt4][ReBr2(CO)4] was isolated and
characterized by (13)C NMR and IR spectroscopy as well as by single-crystal X-ray
diffraction. For technetium, no such intermediate could be identified. The
activation parameters (DeltaH(?) = 110 +/- 7 kJ mol(-1) and DeltaS(?) = 127 +/-
22 J mol(-1) K(-1)) and the observed influences of different ligands and solvents
suggest a dissociative-interchange-type mechanism with a second-order rate
constant for the formation of [NEt4][ReBr2(CO)4], k1 = 0.039 +/- 0.001 M(-1) s(
1) at 274 K. On the basis of variable-temperature NMR experiments, kinetic
simulations, and density functional theory calculations, a complete model for the
CO self-exchange, including all respective rate constants, is reported.
PMID- 27606788
TI - Bring Your Own Device and Nurse Managers' Decision Making.
AB - The Bring Your Own Device phenomenon is important in the healthcare environment
because this trend is changing the workplace in healthcare organizations, such as
British Columbia. At present, there is little research that exists in Canada to
provide a distinct understanding of the complexities and difficulties unique to
this phenomenon within the nursing practice. This study focused on the
experiences and perceptions of nurse managers regarding how they make decisions
on the use of personal handheld devices in the workplace. Telephone interviews (N
= 10) and qualitative descriptive analysis were used. Four major themes emerged:
(1) management perspective, (2) opportunities, (3) disadvantages, and (4)
solutions. Nurse managers and other executives in healthcare organizations and
health information technology departments need to be aware of the practice and
organizational implications of the Bring Your Own Device movement.
PMID- 27606789
TI - Psychometric Testing of the Self-Efficacy for Interdisciplinary Plans of Care
Scale.
AB - Computerized interdisciplinary plans of care have revitalized nurse-centric care
plans into dynamic and meaningful electronic documents. To maximize the benefits
of these documents, it is important to understand healthcare professionals'
attitudes, specifically their confidence, for making computerized
interdisciplinary care plans useful and meaningful documents. The purpose of the
study was to test the psychometric properties of the Self-Efficacy for
Interdisciplinary Plans of Care instrument intended to measure healthcare
professionals' self-efficacy for using such documents. Content validity was
assessed by an expert review panel. Content validity indices ranged from 0.75 to
1.00, with a scale CVI of 0.94. A sample of 389 healthcare providers completed
the 14-item instrument. Principal axis factoring was used to assess factor
structure. The exploratory factor analysis yielded a single-factor structure
accounting for 71.76% of covariance. Cronbach internal consistency coefficient
for the single factor solution was .97. The corrected item-total correlations
ranged from 0.71 to 0.90. The coefficient of stability, during a 2-week period,
with a subset of the sample (n = 38), was estimated at 0.82. The results of this
study suggest that the Self-Efficacy for Interdisciplinary Plans of Care has
sturdy reliability and validity for measuring the self-efficacy of healthcare
providers to make computerized interdisciplinary plans of care meaningful and
useful documents.
PMID- 27606790
TI - Tailored Education to Increase Self-Efficacy for Caregivers of Children With
Asthma: A Randomized Controlled Trial.
AB - We examined the efficacy of a tailored education program using touch-screen
computers for caregivers of young children with asthma, aged 0 to 6 years. Fifty
three caregivers (mean age, 36.54 years; 51 mothers and two fathers) were
recruited during typical visits to a national children's hospital. Caregivers
were assigned randomly to 28 in the tailored education or 25 in the booklet
education groups. The tailored education group received messages generated by a
computer program, and the researchers provided them with counseling. The booklet
education group only received an educational booklet. The primary outcome
variable was parental self-efficacy and its subscales (ie, medication behavior,
environmental behavior, barriers to self-management, and consultation behavior).
The tailored education group showed an increase in barriers to management and
asthma knowledge compared with the booklet education group. Over time,
caregivers' quality of life improved significantly in both groups. Tailored
education programs for caregivers of asthmatic children require further
educational content modifications to match the learners' characteristics more
closely. This study supports the notion that the development of patient education
with tailored computer programs improves parental quality of life of asthma.
PMID- 27606791
TI - Correction to Whispering Gallery Mode Dip Sensor for Aqueous Sensing.
PMID- 27606792
TI - Reactivity of a Nickel Sulfide with Carbon Monoxide and Nitric Oxide.
AB - The reactivity of the "masked" terminal nickel sulfide complex, [K(18-crown
6)][(L(tBu))Ni(II)(S)] (L(tBu) = {(2,6-(i)Pr2C6H3)NC((t)Bu)}2CH), with the
biologically important small molecules CO and NO, was surveyed. [K(18-crown
6)][(L(tBu))Ni(II)(S)] reacts with carbon monoxide (CO) via addition across the
Ni-S bond to give a carbonyl sulfide complex, [K(18-crown
6)][(L(tBu))Ni(II)(S,C:eta(2)-COS)] (1). Additionally, [K(18-crown
6)][(L(tBu))Ni(II)(S)] reacts with nitric oxide (NO) to yield a nickel nitrosyl,
[(L(tBu))Ni(NO)] (2), and a perthionitrite anion, [K(18-crown-6)][SSNO] (3). The
isolation of 3 from this reaction confirms, for the first time, that transition
metal sulfides can react with NO to form the biologically important [SSNO](-)
anion.
PMID- 27606793
TI - Modern drug delivery strategies applied to natural active compounds.
AB - INTRODUCTION: Colloidal drug delivery systems (CDDSs) are innovative carriers
that have been studied in pharmaceutical field from many years to overcome
unfavorable physical and chemical features of synthetic drugs. Recently the use
of CDDS as carriers for phytochemicals has seen an exponential increase which, in
some cases, has led to the rediscovery of ancient and forgotten natural
molecules. Area covered: This article focuses on the main features of CDDS,
particularly micro- and nanoemulsions, vesicular carriers and micro- and
nanoparticles, loaded with natural active compounds. A detailed review of the
literature is presented, introducing the importance of these systems in terms of
their capability to optimize the stability of phytochemicals, their absorption
through biological membranes and their bioavailability. Expert opinion: The
delivery of phytochemicals is problematic due to poor solubility, poor
permeability, low bioavailability, instability in biological milieu and extensive
first-pass metabolism. Global research efforts investigating nanotechnology have
attempted to overcome these limitations rediscovering and, in some cases,
'discovering ex novo' unexpected virtues and benefits associated to these
compounds. The 'nanotechnological approach' can definitely enhance the
pharmacokinetics and therapeutic index of natural active compounds and improve
their performance in therapy.
PMID- 27606794
TI - MuffinInfo: HTML5-Based Statistics Extractor from Next-Generation Sequencing
Data.
AB - Usually, the information known a priori about a newly sequenced organism is
limited. Even resequencing the same organism can generate unpredictable output.
We introduce MuffinInfo, a FastQ/Fasta/SAM information extractor implemented in
HTML5 capable of offering insights into next-generation sequencing (NGS) data.
Our new tool can run on any software or hardware environment, in command line or
graphically, and in browser or standalone. It presents information such as
average length, base distribution, quality scores distribution, k-mer histogram,
and homopolymers analysis. MuffinInfo improves upon the existing extractors by
adding the ability to save and then reload the results obtained after a run as a
navigable file (also supporting saving pictures of the charts), by supporting
custom statistics implemented by the user, and by offering user-adjustable
parameters involved in the processing, all in one software. At the moment, the
extractor works with all base space technologies such as Illumina, Roche, Ion
Torrent, Pacific Biosciences, and Oxford Nanopore. Owing to HTML5, our software
demonstrates the readiness of web technologies for mild intensive tasks
encountered in bioinformatics.
PMID- 27606795
TI - Depression as Measured by PHQ-9 Versus Clinical Diagnosis as an Independent
Predictor of Long-Term Mortality in a Prospective Cohort of Medical Inpatients.
AB - BACKGROUND: Depression has been associated with higher rates of mortality in
medical patients. The aim of the study was to evaluate the impact of depression
in medical inpatients on the rate of mortality during a prolonged follow-up
period. METHOD: This is a prospective follow-up study of a cohort of medical
inpatients assessed during 1997-1998 in medical and surgical units at a tertiary
university hospital in Spain and followed-up for a period ranging between 16.5
and 18 years. Eight hundred three patients were included; 420 (52.3%) were male,
and the mean (SD) age was 41.7 (13.8) years. Main outcome was death for any cause
during follow-up. The original full Patient Health Questionnaire (PHQ) was
administered at baseline as self-report from which the PHQ-9 was derived.
Depressive disorders were assessed using PHQ-9 and a structured clinical
interview (Structured Clinical Interview for Diagnostic and Statistical Manual of
Mental Disorders, Revised Third Edition). RESULTS: Depressive disorders as
defined by PHQ-9 were detected in 206 patients (25.7%), 122 (15.2%) of them
fulfilling criteria for major depression. During follow-up, 152 patients (18.9%)
died. A PHQ score indicating the presence of major depressive disorder predicted
increased mortality (hazard ratio [HR], 2.44; 95% CI, 1.39-4.29), even after
adjusting for important demographic and clinical variables. Similarly, the PHQ-9
score as a continuous measure of depression severity predicted increased
mortality (HR, 1.06; 95% CI, 1.02-1.10). Results were similar for clinical
interview diagnoses of major depression (HR, 2.07; 95% CI, 1.04-4.09).
CONCLUSIONS: Medical inpatients with a PHQ depressive disorder had a nearly 2
fold higher risk of long-term mortality, even after adjustment for several
confounders. Depression severity as represented by the PHQ-9 score was also a
risk factor.
PMID- 27606798
TI - Outbreak of Serogroup C Meningococcal Disease Primarily Affecting Men Who Have
Sex with Men - Southern California, 2016.
AB - During March 4-August 11, 2016, 25 outbreak-associated cases of meningococcal
disease, including two deaths (8% case-fatality ratio), were reported in Southern
California. Twenty-four of the cases were caused by serogroup C Neisseria
meningitidis (NmC) and one by N. meningitidis with an undetermined serogroup
(Figure). On June 24, 2016, in response to this increase in NmC cases, primarily
among men who have sex with men (MSM) in Los Angeles County, the city of Long
Beach, and Orange County, the California Department of Public Health (CDPH)
issued a press release and health advisory, declaring an outbreak of NmC in
Southern California (1).
PMID- 27606796
TI - Prenatal Undernutrition and Autonomic Function in Adulthood.
AB - OBJECTIVES: Early-life adversity has been shown to be associated with
cardiovascular disease and mortality in later life, but little is known about the
mechanisms that underlie this association. Prenatal undernutrition, a severe
early-life stressor, is associated with double the risk of coronary heart disease
and increased blood pressure responses to psychological stress. In the present
study, we tested the hypothesis that prenatal undernutrition induces alterations
in the autonomic nervous system, which may increase the risk of developing heart
disease. METHODS: We studied autonomic function in 740 men and women (mean [SD]
age, 58 [0.9] years) who were members of the Dutch famine birth cohort. We
compared those exposed to famine during early (n = 64), mid (n = 107), or late
gestation (n = 127) to those unexposed to famine in utero (n = 442). Participants
underwent a series of 3 psychological stressors (Stroop, mirror tracing, and
speech) while their blood pressure and heart rate were recorded continuously.
RESULTS: Data had sufficient quality in 602 participants for derivation of
autonomic function indices by spectral analysis. The stress protocol led to
significant sample-level changes in systolic blood pressure, heart rate, and all
cardiovascular control measures (all p values < .001). None of the autonomic
function parameters, at rest or in response to stress, differed significantly
(all p values > .050) according to prenatal famine exposure. CONCLUSIONS:
Prenatal undernutrition was not associated with autonomic function in late
adulthood. We conclude that altered autonomic function does not seem to explain
our previous findings of increased coronary heart disease risk among those
exposed to famine prenatally.
PMID- 27606799
TI - Spin-Adapted Formulation and Implementation of Density Cumulant Functional Theory
with Density-Fitting Approximation: Application to Transition Metal Compounds.
AB - Density cumulant functional theory (DCT) has recently emerged as an attractive ab
initio approach for the treatment of electron correlation. In its orbital
optimized formulation (ODC-12) [J. Chem. Phys. 139, 204110 (2013)], DCT has been
shown to provide reliable results for a variety of challenging chemical systems.
Among the attractive properties of DCT are its size-consistency and size
extensivity, as well as the efficient computation of the molecular properties and
analytic gradients. In this work, we present a new formulation and implementation
of DCT that takes advantage of spin adaptation and the density-fitting
approximation (DF-ODC-12). Our new spin-adapted DF-ODC-12 implementation is more
efficient than the previous ODC-12 implementation with up to a ~12-fold speed-up.
We demonstrate the capabilities of DF-ODC-12 with a study of transition metal
compounds, which require high levels of electron correlation treatment. For
transition metal carbonyl complexes [Fe(CO)5, Cr(CO)6] and the ferrocene molecule
[Fe(Cp)2], the DF-ODC-12 equilibrium parameters and bond dissociation energies
extrapolated to the complete basis set limit are in very good agreement with
reference data derived from experiment.
PMID- 27606797
TI - Childhood Trauma and Adult Risk Factors and Disease in Hispanics/Latinos in the
US: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Sociocultural Ancillary Study.
AB - OBJECTIVE: Adverse childhood experiences (ACEs) are implicated in diseases of
adulthood. We report the prevalence of ACEs in Hispanics/Latinos in the US and
their association with major risk factors and diseases in adulthood. METHODS:
Data from the Sociocultural Ancillary Study of the Hispanic Community Health
Study/Study of Latinos (HCHS/SOL) were used. The Sociocultural Ancillary Study of
the Hispanic Community Health Study/Study of Latinos is an epidemiological study
conducted in four urban communities in the US: Bronx, Chicago, Miami, and San
Diego. The analytic sample comprised 5117 participants, ages 18 to 74 at
baseline. Linear and logistic models, adjusted for sociodemographic factors, were
used to examine associations of ACEs and risk factors (depressive symptoms,
obesity, smoking, and alcohol use) and chronic disease (coronary heart disease,
stroke, diabetes, asthma, chronic obstructive pulmonary disease, and cancer); the
latter were also adjusted for risk factors. RESULTS: Most participants (77.2%)
experienced at least one ACE, and 28.7% experienced four or more. Adverse
childhood experiences were common among all ancestry groups, with variability
among them. Prevalence of four or more ACEs was higher among women than men
(31.2% and 25.8%, respectively). Adverse childhood experiences were associated
with depressive symptoms, body mass index, smoking, alcohol use, cancer, coronary
heart disease, and chronic obstructive pulmonary disease, but not asthma,
diabetes, or stroke. Associations were not moderated by social support.
CONCLUSIONS: Adverse childhood experiences are prevalent among US
Hispanics/Latinos and are involved in disease in adulthood. The apparent higher
prevalence of ACEs in US Hispanics/Latinos did not correspond with stronger
associations with disease. Further studies are needed to identify factors that
may moderate the associations of ACE with adult disease.
PMID- 27606801
TI - Optical chiral metamaterials: a review of the fundamentals, fabrication methods
and applications.
AB - Optical chiral metamaterials have recently attracted considerable attention
because they offer new and exciting opportunities for fundamental research and
practical applications. Through pragmatic designs, the chiroptical response of
chiral metamaterials can be several orders of magnitude higher than that of
natural chiral materials. Meanwhile, the local chiral fields can be enhanced by
plasmonic resonances to drive a wide range of physical and chemical processes in
both linear and nonlinear regimes. In this review, we will discuss the
fundamental principles of chiral metamaterials, various optical chiral
metamaterials realized by different nanofabrication approaches, and the
applications and future prospects of this emerging field.
PMID- 27606802
TI - Population Pharmacodynamic Model for Bayesian Prediction of Myelosuppression
Profiles Based on Routine Clinical Data after Gemcitabine and Carboplatin
Treatment.
AB - BACKGROUND: Hematological toxicity is a serious adverse event and is often a dose
limiting factor in anticancer drugs. The objective of the present study was to
develop a modeling and simulation (M&S) procedure for predictions of time course
profiles of blood cell counts that reflect myelosuppression profiles. METHODS: A
method for Bayesian prediction of myelosuppression profiles during chemotherapy
using a population pharmacodynamic model is proposed, and predictabilities of
nadir values and times to nadir (Tnadir) after gemcitabine and carboplatin
treatment were evaluated. The model is based on an equation for Erlang
distribution, which we previously proposed, and it explains time course profiles
of platelet (PLT), red blood cell (RBC) and white blood cell (WBC). RESULTS AND
CONCLUSION: PLT, RBC and WBC counts were retrospectively collected from 61 time
courses (a total of 472 points) of 27 cancer patients. Predictive performance by
a one-point Bayesian prediction was evaluated using data from day 8 in
consideration of applicability to outpatients. Some good predictability was
obtained for nadir values with some exceptions for PLT and RBC, whereas the
predictability of Tnadir was insufficient. Although the predictability was not
acceptable enough, this M&S approach could be used for supportive care during
cancer chemotherapy.
PMID- 27606803
TI - Clinical Manifestation of Parkinson's Disease in Association with Rapid Eye
Movement Sleep Behavior Disorder Onset.
AB - AIMS: To confirm whether the presence and/or timing of rapid eye movement sleep
behavior disorder (RBD) onset were associated with differences in clinical
features of Parkinson's disease (PD), clinical characteristics of PD patients
with RBD occurring before and after PD diagnosis were investigated. METHODS:
Consecutive PD patients were enrolled between July 2011 and February 2012. RBD
questionnaire Hong Kong and clinical interviews were used to identify RBD
symptoms and onsets. All patients underwent evaluations to collect clinical and
treatment information. RESULTS: Of all 79 PD patients, 21 (26.6%) and 22 (27.8%)
patients had RBD prior to (RBD-PD) and after PD diagnosis (PD-RBD), respectively.
Thirty-six (45.6%) PD patients reported no RBD at the time of study (PD-NRBD). PD
RBD had similar clinical features as PD-NRBD did except that Epworth sleepiness
scale score was significantly higher in PD-RBD (p = 0.04). Compared to PD-RBD and
PD-NRBD, RBD-PD had a higher frequency of reporting excessive daytime sleepiness
(p = 0.019, p = 0.008, respectively) and constipation (p = 0.046, p = 0.032,
respectively). CONCLUSION: Our preliminary results suggest that RBD-PD might be
clinically different from PD-RBD, which appears to share similar characteristics
with PD-NRBD, regarding only non-motor functions.
PMID- 27606805
TI - Telomerase in Acute Myeloid Leukemia: A Molecular Update on Diagnosis, Prognosis,
and Treatment.
AB - It is expected that 10,460 patients will die from acute myeloid leukemia (AML) in
the United States in 2016. Despite progress in clinical management, AML patients
still have a 25.9% survival rate in the U.S. Researchers have sought to further
understand this hematological malignancy and a number of studies have focused on
unveiling the role of telomerase in disease initiation, progression, and
maintenance. Though the role of telomerase in diagnosis has remained relatively
static, its role in prognosis and treatment has become much clearer. While
variants in TERT and TERC have been associated with worse clinical outcomes,
telomerase and survivin co-expression can predict improved clinical outcomes. In
regards to treatment, novel therapies such as mesoindigo and sodium metaarsenite
provide new insights in clinical management. The use of leukemic stem cells in
mouse models has shown promising results as well. Herein, we provide an update on
the role of telomerase in AML through a survey of recent literature, focusing on
the diagnosis, prognosis, and treatment of AML.
PMID- 27606806
TI - Association of chronic obstructive pulmonary, coronary artery, or peripheral
artery disease with abdominal aortic aneurysm rupture.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD), coronary artery disease
(CAD), and peripheral artery disease (PAD) are positively associated with
abdominal aortic aneurysm (AAA) presence. It remains unclear, however, whether
these 3 comorbidities are associated with AAA rupture. To assess the association
of COPD, CAD, or PAD with AAA rupture, we reviewed currently available studies
with a systematic literature search and meta-analytic estimates. METHODS:
Databases including MEDLINE and EMBASE were searched through December 2015 using
PubMed and OVID. For each study, data regarding prevalence of COPD, CAD, or PAD
in both the ruptured and non-ruptured groups were used to generate odds ratios
(ORs) for rupture and 95% confidence intervals (CIs). Study-specific estimates
were combined using inverse variance-weighted averages of logarithmic ORs in a
random-effects model. RESULTS: Our search identified 9 relevant studies including
data on a total of 8873 AAA patients (rupture, 1241; non-rupture, 7632). Pooled
analyses demonstrated that COPD was significantly and positively (OR, 1.51; 95%
CI, 1.06 to 2.16; P=0.02), CAD was not significantly (OR, 0.83; 95% CI, 0.43 to
1.60; P=0.58), and PAD tended to be negatively (though non-significantly)
associated with AAA rupture (OR, 0.44; 95% CI, 0.16 to 1.23; P=0.12).
CONCLUSIONS: Our analysis suggests that COPD is positively associated with AAA
rupture, CAD is not associated with it, and PAD tends to be negatively associated
with it. Further investigations would be required to understand precise
mechanisms regarding the association of COPD, CAD, and PAD with AAA presence,
growth, and rupture.
PMID- 27606804
TI - Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic
Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium.
AB - Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular
T cell immune response which may contribute towards development of accelerated
immune senescence and vascular disease in older people. Virus-specific CD8+ T
cell responses have been investigated extensively through the use of HLA-peptide
tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a
range of HLA class II-peptide tetramers to investigate the phenotypic and
transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We
show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can
reach up to 24% in some individuals (range 0.01-24%). CMV-specific CD4+ T cells
display a highly differentiated effector memory phenotype and express a range of
cytokines, dominated by dual TNF-alpha and IFN-gamma expression, although
substantial populations which express IL-4 were seen in some donors. Microarray
analysis and phenotypic expression revealed a profile of unique features. These
include the expression of CX3CR1, which would direct cells towards fractalkine on
activated endothelium, and the beta2-adrenergic receptor, which could permit
rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic
profile with high level expression of granzyme B and perforin, a pattern which
increases further during aging. In addition CMV-specific CD4+ T cells demonstrate
strong cytotoxic activity against antigen-loaded target cells when isolated
directly ex vivo. PD-1 expression is present on 47% of cells but both the
intensity and distribution of the inhibitory receptor is reduced in older people.
These findings reveal the marked accumulation and unique phenotype of CMV
specific CD4+ T cells and indicate how such T cells may contribute to the
vascular complications associated with CMV in older people.
PMID- 27606809
TI - Copper-Catalyzed Addition of H-P(O) Bonds to Arynes.
AB - An efficient P-arylation of secondary phosphine oxides has been achieved through
the ligand-free copper-catalyzed addition of H-P(O) bonds to in situ generated
arynes at room temperature. This transformation provides a straightforward route
to the formation of the aryl-P bond with wide functional group compatibility,
which produces arylphosphine oxides in up to 99% yield.
PMID- 27606807
TI - Asian venous thromboembolism guidelines: updated recommendations for the
prevention of venous thromboembolism.
AB - The Asian venous thromboembolism (VTE) prophylaxis guidelines were first
published in 2012. Since its first edition, the Asian Venous Thrombosis Forum
(AVTF) working group have updated the Asian VTE epidemiology and reviewed issues
that were not addressed in the previous guidelines. The authors noted that the
rising incidence of VTE across Asia may be attributable to aging population,
dietary changes, and increasing incidence of obesity and diabetes. The new
additions in the guideline include role of thrombophilia in VTE, bleeding risk in
Asians, individual risk assessment, updates in the prevention of VTE in medically
ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of
primary thrombophilia in perioperative VTE is still unclear. The secondary risk
factors, however, are similar between Asians and Caucasians. The group found no
evidence of increased risk of bleeding while using pharmacological agents,
including the use of novel anti-coagulants. At present, Caprini risk assessment
model is widely used for individual risk assessment. Further validation of this
model is needed in Asia. In medically ill patients, pharmacological agents are
preferred if there is no bleeding risk. Intermittent pneumatic compression device
(IPC) is recommended in patients with bleeding risk but we do not recommend using
graduated compressive stockings. In bariatric patients, data on VTE is lacking in
Asia. We recommend following current international guidelines. A high index of
suspicion should be maintained during postbariatric surgery to detect and
promptly treat portomesenteric venous thrombosis. Different cancer types have
different thrombotic risks and the types of surgery influence to a large extent
the overall VTE risk. Cancer patients should receive further risk assessment. In
patients with higher thrombotic risk, either due to predisposing risk or
concomitant surgery, low molecular weight heparin is indicated. Different
countries appear to have different incidence of VTE following trauma and major
orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main
method and additional pharmacological prophylaxis if the thrombotic risk is high.
As for obstetric practice, we propose adherence to the UK Greentop guideline that
is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis
implementation in the region, we propose that there should be better health
education, establishment of hospital-based guidelines and multidisciplinary
collaboration.
PMID- 27606808
TI - The Statistical Determinants of the Speed of Motor Learning.
AB - It has recently been suggested that movement variability directly increases the
speed of motor learning. Here we use computational modeling of motor adaptation
to show that variability can have a broad range of effects on learning, both
negative and positive. Experimentally, we also find contributing and decelerating
effects. Lastly, through a meta-analysis of published papers, we verify that
across a wide range of experiments, movement variability has no statistical
relation with learning rate. While motor learning is a complex process that can
be modeled, further research is needed to understand the relative importance of
the involved factors.
PMID- 27606810
TI - Potential Role of Hyperglycemia in Fetoplacental Endothelial Dysfunction in
Gestational Diabetes Mellitus.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with structural and
functional alterations in various tissues including endothelial dysfunction. The
aim of this study was to explore the effects of hyperglycemia on fibroblast
growth factor 2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated
placental angiogenesis and the underlying molecular signaling mechanisms.
METHODS: The density of fetal placental capillaries was examined using
immunohistochemistry. Human umbilical vein endothelial cells (HUVECs) derived
from GDM (dHUVECs) and normal healthy patients (nHUVECs) were used as cell models
in this study. Cell proliferation, migration and tube formation were measured
with an MTS assay, a transwell system and a matrigel assay, respectively. The
activation of ERK1/2 was analyzed with Western blot. The specific inhibitor of
extracellular signal-regulated kinases 1/2 (ERK1/2) PD98059 was used to elucidate
the involved signaling pathway. RESULTS: GDM did not alter the capillary density
of the fetus-placenta. Both the GDM and hyperglycemic conditions inhibited the
proliferation of the FGF2- but not the VEGF-stimulated HUVECs and the basal
migratory capacity. Hyperglycemic condition significantly inhibited tube
formation and ex vivo angiogenesis. Moreover, hyperglycemia inhibited the FGF2-
but not the VEGF-induced activation of ERK1/2. PD98059 significantly inhibited
the FGF2-activated ERK1/2 phosphorylation and the FGF2-stimulated cell
proliferation in HUVECs. CONCLUSION: Both GDM and hyperglycemia may impair
placental angiogenesis by reducing HUVEC proliferation, migration and tube
formation. Hyperglycemia-inhibited cell proliferation stimulated by FGF2 probably
contributed to the suppression of the MEK1/2/ERK1/2 pathways in the HUVECs.
PMID- 27606811
TI - Synchrotron-Based Highest Resolution Terahertz Spectroscopy of the nu24 Band
System of 1,2-Dithiine (C4H4S2): A Candidate for Measuring the Parity Violating
Energy Difference between Enantiomers of Chiral Molecules.
AB - The chiral C2 symmetric molecule 1,2-dithiine (1,2-dithia-3,5-hexadiene, C4H4S2)
has been identified as a possible candidate for measuring the parity violating
energy difference between enantiomers. We report here the observation and
analysis of the low-frequency fundamental nu24 using highest resolution
synchrotron-based interferometric Fourier transform infrared (FTIR) spectroscopy
in the terahertz range with a band center of nu0 = 6.95375559 THz (nu0 =
231.952319 (10) cm-1) and two related hot bands, the (nu13 + nu24) <- nu13 band
at nu0 = 6.97256882 THz (nu0 = 232.579861 (33) cm-1) and the 2nu24 <- nu24 band
at nu0 = 7.01400434 THz (nu0 = 233.962001 (14) cm-1). This success in the
difficult analyses of the THz spectrum of a complex chiral molecule of importance
for fundamental tests on molecular parity violation is enabled by the ideal setup
of an FTIR experiment of currently unique resolution with the very stable and
bright synchrotron radiation at the Swiss Light Source (SLS).
PMID- 27606812
TI - Improving Diagnostic Accuracy of Dermoscopically Equivocal Pink Cutaneous Lesions
with Reflectance Confocal Microscopy in Telemedicine Settings: Double Reader
Concordance Evaluation of 316 Cases.
AB - BACKGROUND: Solitary pink lesions in differential diagnosis with
hypopigmented/amelanotic melanoma present a diagnostic challenge in daily
practice and are regularly referred for second expert opinion. Reflectance
confocal microscopy (RCM) has been shown to improve diagnostic accuracy of
dermoscopically equivocal pink lesions. No studies have been performed to
evaluate the effect of adding a second expert reader and automatic removal of
lesions with discordant management recommendations and its potential effect on
diagnostic sensitivity and final management of these lesions in retrospective or
telemedicine settings. OBJECTIVE: To improve diagnostic accuracy and reduce
potential mismanagement of dermoscopically equivocal pink cutaneous lesions by
implementing double reader concordance evaluation of RCM images. METHODS: 316
dermoscopically equivocal pink lesions with dermoscopy-RCM image sets were
evaluated retrospectively. Accuracy of three readers was evaluated by single
reader evaluation of dermoscopy only and dermoscopy-RCM image sets and finally by
double reader evaluation of dermoscopy-RCM image sets. Lesions with discordant
diagnosis between two readers were automatically recommended for excision.
RESULTS: Dermoscopy only evaluation resulted in an overall sensitivity of 95.9%
and specificity of 33.6%, with 1 of 12 amelanotic melanomas mismanaged.
Dermoscopy-RCM image set single reader evaluation resulted in an overall
sensitivity of 93.9% and overall specificity of 54.2%, with 1 of 12 melanomas
mismanaged. Dermoscopy-RCM image set double reader concordance evaluation
resulted in an overall sensitivity of 98.3% and specificity of 42.7%, with no
amelanotic melanoma mismanagement. CONCLUSION: Evaluation of dermoscopy-RCM image
sets of equivocal pink lesions by a single reader in telemedicine settings is
limited by the potential for misdiagnosis of dangerous malignant lesions. Double
reader concordance evaluation with automatic referral of lesions for removal in
the case of discordant diagnosis improves the diagnostic sensitivity in this
subset of lesions and reduce potential misdiagnosis in settings where a second
expert opinion may be employed.
PMID- 27606813
TI - Serum Amylase Levels in Relation to Islet beta Cell Function in Patients with
Early Type 2 Diabetes.
AB - OBJECTIVE: The insulin-pancreatic acinar axis may play a major role in pancreatic
function. Amylase is an exocrine enzyme that is produced by pancreatic acinar
cells, and low serum amylase levels may be associated with endocrine diseases,
such as metabolic syndrome and diabetes. We hypothesized that low serum amylase
levels may be associated with impaired islet beta cell function in type 2
diabetes. Therefore, we investigated the relationship between the serum amylase
levels and islet beta cell function in patients with early type 2 diabetes.
METHODS: The cross-sectional study recruited 2327 patients with a mean of 1.71+/
1.62 years since their diagnosis of type 2 diabetes, and all participants were
treated with lifestyle intervention alone. Serum amylase levels, the 75-g oral
glucose tolerance test (OGTT) and metabolic risk factors were examined in all
participants. The insulin sensitivity index (Matsuda index, ISIMatsuda) and
insulin secretion index (ratio of total area-under-the-insulin-curve to glucose
curve, AUCins/glu) were derived from the OGTT. Integrated islet beta cell
function was assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
(ISIMatsuda multiplied by AUCins/glu). RESULTS: Serum amylase levels in the
normal range were significantly correlated with ISIMatsuda, AUCins/glu and ISSI-2
(r = 0.203, 0.246 and 0.413, respectively, p<0.001). The association of the serum
amylase levels with ISSI-2 (adjusted r = 0.363, p<0.001) was closer than the
association with ISIMatsuda (adjusted r = 0.191, p<0.001) and AUCins/glu
(adjusted r = 0.174, p<0.001) after adjusting for the anthropometric indices,
time since the diagnosis of diabetes, lipid profiles, uric acid levels, estimated
glomerular filtration rate, HbA1c levels, smoking and drinking using the partial
correlation test. After adjusting for these metabolic risk factors in the
multivariate regression analysis with the amylase levels as the dependent
variable, ISSI-2 was the major independent contributor to the serum amylase
levels (beta = 0.416, t = 21.72, p<0.001). Meanwhile, in a comparison of the
groups with the highest and lowest quartiles of serum amylase levels, the mean
difference in logISSI-2 was 0.902 (95% CI 0.823 to 0.982), and after adjusting
for metabolic risk factors, the mean difference in logISSI-2 was 0.610 (0.537 to
0.683). CONCLUSIONS: Serum amylase levels in the normal range are positively
associated with integrated islet beta cell function in patients with early type 2
diabetes, as assessed by ISSI-2.
PMID- 27606814
TI - Isolation, Culture and Identification of Choriocarcinoma Stem-Like Cells from the
Human Choriocarcinoma Cell-Line JEG-3.
AB - BACKGROUND/AIMS: Cancer stem cells (CSCs) exhibit enhanced proliferative capacity
and resistance to chemotherapy; however, choriocarcinoma CSCs have not yet been
reported. In this study the human choriocarcinoma cell line JEG-3 was cultured in
serum free media, and the characteristics of suspension and parental adherent JEG
3 cells were compared. METHODS: Cell proliferation, colony-formation, soft agar
clonogenicity, and transwell invasion assays were performed in vitro, and tumor
xenografts in BALB/c nude mice were used to evaluate stem cell properties.
RESULTS: In serum-supplemented medium (SSM), JEG-3 cells were 4.51 +/- 1.71%
CD44+, 7.67 +/- 2.67% CD133+, and 13.85 +/- 2.95% ABCG2+. In serum-free medium
(SFM), the expression of these markers increased to 53.08 +/- 3.15%, 47.40 +/-
2.67%, and 78.70 +/- 7.16%, respectively. Moreover, suspension JEG-3 cells
exhibited enhanced colony-formation capability as well as invasive and
proliferative ability in vitro, alongside enhanced tumorigenic properties in
vivo. Suspension JEG-3 cells also exhibited resistance to the chemotherapeutic
drugs methotrexate, fluorouracil and etoposide. When seeded in serum supplemented
medium, suspension JEG-3 cells readopted an adherent phenotype and continued to
differentiate with no significant difference in the morphology between suspension
and parent cells. CONCLUSION: In this study, choriocarcinoma stem-like cells
(CSLCs) were isolated from the human choriocarcinoma JEG-3 cell line by SFM
culture and characterized.
PMID- 27606815
TI - Ocular manifestations of autoimmune polyendocrinopathy syndrome type 1.
AB - PURPOSE OF REVIEW: The ocular manifestations in autoimmune polyendocrinopathy
syndrome type 1 (APS1) are frequent and have a poor prognosis. The phenotype of
these APS1-associated ocular features have been recently characterized in
molecularly confirmed patients with APS1. RECENT FINDINGS: Keratopathy and
retinopathy can be severe manifestations of APS1. Heterogeneous corneal
involvement can be observed, ranging from minimal superficial punctate staining
to severe stromal scarring with deep corneal neovascularization. This phenotypic
heterogeneity, observed even in patients with identical AIRE mutations, is
suggestive of a poor genotype-phenotype correlation. Similarly, in patients with
retinopathy, peripheral pigmentary changes are noted in all cases, yet with
heterogeneous severity, ranging from isolated patchy atrophy of the retinal
pigment epithelium to a retinitis pigmentosa-like fundus. Macular atrophy with
vision loss is found in most cases. The severity of ophthalmic findings is
uncorrelated to that of systemic manifestations. An autoimmune origin with
specific autoantibodies directed against corneal and/or retinal autoantigens is
the main mechanism believed to be responsible for the ocular manifestations of
APS1. SUMMARY: Progressive keratopathy and/or retinopathy can lead to severe
visual loss and pain in patients with APS1. Although no treatment has shown
efficacy regarding the APS1-associated ocular manifestations, ophthalmologic
examinations are recommended in these patients.
PMID- 27606816
TI - Formulation, in vitro evaluation and kinetic analysis of chitosan-gelatin bilayer
muco-adhesive buccal patches of insulin nanoparticles.
AB - The present study was performed to optimise the formulation of a muco-adhesive
buccal patch for insulin nanoparticles (NPs) delivery. Insulin NPs were
synthesised by an ionic gelation technique using N-di methyl ethyl chitosan
cysteine (DMEC-Cys) as permeation enhancer biopolymer, tripolyphosphate (TPP) and
insulin. Buccal patches were developed by solvent-casting technique using
chitosan and gelatine as muco-adhesive polymers. Optimised patches were embedded
with 3 mg of insulin-loaded NPs with a homogeneous distribution of NPs in the
muco-adhesive matrix, which displayed adequate physico-mechanical properties. The
drug release characteristics, release mechanism and kinetics were investigated.
Data fitting to Peppas equation with a correlation coefficient indicated that the
mechanism of drug release followed an anomalous transport that means drug release
was afforded through drug diffusion along with polymer erosion. In vitro drug
release, release kinetics, physical and mechanical studies for all patch
formulations reflected the ideal characteristics of this buccal patch for the
delivery of insulin NPs.
PMID- 27606817
TI - Identifying Anomalous Citations for Objective Evaluation of Scholarly Article
Impact.
AB - Evaluating the impact of a scholarly article is of great significance and has
attracted great attentions. Although citation-based evaluation approaches have
been widely used, these approaches face limitations e.g. in identifying anomalous
citations patterns. This negligence would inevitably cause unfairness and
inaccuracy to the article impact evaluation. In this study, in order to discover
the anomalous citations and ensure the fairness and accuracy of research outcome
evaluation, we investigate the citation relationships between articles using the
following factors: collaboration times, the time span of collaboration, citing
times and the time span of citing to weaken the relationship of Conflict of
Interest (COI) in the citation network. Meanwhile, we study a special kind of
COI, namely suspected COI relationship. Based on the COI relationship, we further
bring forward the COIRank algorithm, an innovative scheme for accurately
assessing the impact of an article. Our method distinguishes the citation
strength, and utilizes PageRank and HITS algorithms to rank scholarly articles
comprehensively. The experiments are conducted on the American Physical Society
(APS) dataset. We find that about 80.88% articles contain contributed citations
by co-authors in 26,366 articles and 75.55% articles among these articles are
cited by the authors belonging to the same affiliation, indicating COI and
suspected COI should not be ignored for evaluating impact of scientific papers
objectively. Moreover, our experimental results demonstrate COIRank algorithm
significantly outperforms the state-of-art solutions. The validity of our
approach is verified by using the probability of Recommendation Intensity.
PMID- 27606819
TI - Go East for Better Honey Bee Health: Apis cerana Is Faster at Hygienic Behavior
than A. mellifera.
AB - The poor health status of the Western honey bee, Apis mellifera, compared to its
Eastern counterpart, Apis cerana, is remarkable. This has been attributed to
lower pathogen prevalence in A. cerana colonies and to their ability to survive
infestations with the ectoparasitic mite, Varroa destructor. These properties
have been linked to an enhanced removal of dead or unhealthy immature bees by
adult workers in this species. Although such hygienic behavior is known to
contribute to honey bee colony health, comparative data of A. mellifera and A.
cerana in performing this task are scarce. Here, we compare for the first time
the removal of freeze-killed brood in one population of each species and over two
seasons in China. Our results show that A. cerana was significantly faster than
A. mellifera at both opening cell caps and removing freeze-killed brood. The fast
detection and removal of diseased brood is likely to limit the proliferation of
pathogenic agents. Given our results can be generalized to the species level, a
rapid hygienic response could contribute to the better health of A. cerana.
Promoting the fast detection and removal of worker brood through adapted breeding
programs could further improve the social immunity of A. mellifera colonies and
contribute to a better health status of the Western honey bee worldwide.
PMID- 27606820
TI - Lapse in Institutional Animal Care and Use Committee Continuing Reviews.
AB - The United States federal animal welfare regulations and the Public Health
Service Policy on Humane Care and Use of Laboratory Animals require that
institutional animal care and use committees (IACUCs) conduct continuing reviews
of all animal research activities. However, little is known about the lapse rate
of IACUC continuing reviews, and how frequently investigators continue research
activities during the lapse. It is also not clear what factors may contribute to
an institution's lapse in IACUC continuing reviews. As part of the quality
assurance program, the Department of Veterans Affairs (VA) has collected
performance metric data for animal care and use programs since 2011. We analyzed
IACUC continuing review performance data at 74-75 VA research facilities from
2011 through 2015. The IACUC continuing review lapse rates improved from 5.6% in
2011 to 2.7% in 2015. The rate of investigators continuing research activities
during the lapse also decreased from 47.2% in 2012 to 7.4% in 2015. The type of
IACUCs used and the size of animal research programs appeared to have no effect
in facility's rates of lapse in IACUC continuing reviews. While approximately 80%
of facilities reported no lapse in IACUC continuing reviews, approximately 14% of
facilities had lapse rates of >10% each year. Some facilities appeared to be
repeat offenders. Four facilities had IACUC lapse rates of >10% in at least 3 out
of 5 years, suggesting a system problem in these facilities requiring remedial
actions to improve their IACUC continuing review processes.
PMID- 27606818
TI - Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine
Reproductive and Respiratory Virus (PRRSV) and Actinobacillus pleuropneumoniae
(A. pleuropneumoniae) in Young Pigs.
AB - Until today, anti-microbial drugs have been the therapy of choice to combat
bacterial diseases. Resistance against antibiotics is of growing concern in man
and animals. Stress, caused by demanding environmental conditions, can reduce
immune protection in the host, influencing the onset and outcome of infectious
diseases. Therefore psychoneuro-immunological intervention may prove to be a
successful approach to diminish the impact of diseases and antibiotics use. This
study was designed to investigate the effect of social and environmental
enrichment on the impact of disease, referred to as "disease susceptibility", in
pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight
pigs were raised in four pens under barren conditions and twenty-eight other pigs
were raised in four pens under enriched conditions. In the enriched pens a
combination of established social and environmental enrichment factors were
introduced. Two pens of the barren (BH) and two pens of the enriched housed (EH)
pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens
in each housing treatment served as control groups. We tested if differences in
disease susceptibility in terms of pathological and clinical outcome were related
to the different housing regimes and if this was reflected in differences in
behavioural and immunological states of the animals. Enriched housed pigs showed
a faster clearance of viral PRRSV RNA in blood serum (p = 0.014) and
histologically 2.8 fold less interstitial pneumonia signs in the lungs (p =
0.014). More barren housed than enriched housed pigs developed lesions in the
lungs (OR = 19.2, p = 0.048) and the lesions in the barren housed pigs showed a
higher total pathologic tissue damage score (p<0.001) than those in enriched
housed pigs. EH pigs showed less stress-related behaviour and differed
immunologically and clinically from BH pigs. We conclude that enriched housing
management reduces disease susceptibility to co-infection of PRRSV and A.
pleuropneumoniae in pigs. Enrichment positively influences behavioural state,
immunological response and clinical outcome in pigs.
PMID- 27606821
TI - Application of a parametric model in the mortality risk analysis of ICU patients
with severe COPD.
AB - OBJECTIVE: To evaluate the mortality risk factors of patients with severe chronic
obstructive pulmonary disease (COPD) in the intensive care unit (ICU) by
utilizing parametric model of survival analysis, and to estimate patients'
prognoses based on the risk and survival functions in the model. METHODS: The
clinical data and outcomes of COPD patients admitted to a respiratory intensive
care unit (RICU) at Beijing Chao-Yang Hospital from January 2009 to June 2014
were prospectively collected. Based on the clinical outcomes, these patients were
divided into a survival group and a death group. A univariate analysis was
conducted to identify statistically significant variables. According to the
distribution characteristics of these data, residual plots were prepared for an
exponential model, a Weibull model and a Gamma model. The Gamma model was
determined to be the best fitted for these data and was used as the analytical
tool. Therefore, the variables with differences obtained from the univariate
analysis were put into the Gamma model to determine the patients' mortality risk
factors. The risk and survival functions were also generated according to the
model formula. RESULTS: A total of 160 patients (111 survival, 49 death) were
enrolled. The univariate analysis showed that, compared with the survival group,
patients in the death group had higher Charlson Comorbidity Index score (CCI),
higher body temperature, higher white blood cell counts, higher proportions of
neutrophils, higher serum creatinine levels and higher pH levels; lower resting
carbon dioxide pressure (PCO2 ); and more cases complicated with invasive
pulmonary aspergillosis (IPA). A further analysis with the Gamma model revealed
that concurrent or non-concurrent IPA, white blood cell count, pH level and PCO2
were associated with the patients' mortality risk and that the predicted value
(PV) of the patients' mortality risk = 2.8655 + 0.4070 * IPA + 0.0048 * WBC +
0.0049 * pH - 0.0097 * PCO2 . Moreover, the survival function formula was
obtained according to the Gamma model: S(x) = 1 - I (0.7507 x, -3.3773), where I
is an incomplete gamma function. CONCLUSION: Formula generated from parametric
model may help to predict the prognosis of patients with severe COPD in ICU, and
this method need to be evaluated in further studies. According to our formula,
IPA is an important risk factor of mortality for patients with severe COPD in the
ICU.
PMID- 27606822
TI - Assessment of Nonalcoholic Fatty Liver Disease in Rats Using Quantitative Dynamic
Contrast-Enhanced MRI.
AB - PURPOSE: To evaluate the usefulness of dynamic contrast-enhanced magnetic
resonance imaging (DCE-MRI) in the assessment of nonalcoholic fatty liver disease
(NAFLD) severity. MATERIALS AND METHODS: Liver DCE-MRI at 3.0T was performed in
36 adult Sprague-Dawley rats with methionine choline-deficient diet-induced NAFLD
and 10 untreated control rats. Pharmacokinetic parameters of DCE-MRI including
Ktrans , Kep , Ve , Vp , and hepatic portal index (HPoI) were measured using the
dual-input extended Tofts model. Animals were categorized as normal (n = 10),
simple steatosis (SS, n = 11), borderline nonalcoholic steatohepatitis (bNASH, n
= 20), and NASH (n = 5) subgroups according to the NAFLD activity score system,
and classified into F0 (n = 24), F1 (n = 11), F2 (n = 7), and F3 (n = 4)
subgroups according to an established scoring system. DCE-MRI parameters were
compared. Receiver operating characteristic analyses were performed to assess the
diagnostic performance of various DCE-MRI parameters in grading NAFLD activity
and staging liver fibrosis. RESULTS: Ktrans and HPoI were elevated with
increasing severity of NAFLD activity and increased fibrosis stage. The areas
under the receiver operating characteristic curve (AUROCs) of HPoI ranged from
0.895-0.951 for discriminating between different grades of NAFLD activity, and
the AUROC was 0.852 for discriminating F0 stage from overall F1-F3 stages. The
AUROC of Ktrans for discriminating non-NASH from bNASH and NASH groups was 0.968,
and 0.898 for discriminating between normal and overall fibrosis groups.
CONCLUSION: DCE-MRI may play a role in assessing NAFLD severity. LEVEL OF
EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1485-1493.
PMID- 27606824
TI - Corrigendum.
PMID- 27606823
TI - Magnetothermal Convection of Water with the Presence or Absence of a Magnetic
Force Acting on the Susceptibility Gradient.
AB - Heat transfer of magnetothermal convection with the presence or absence of the
magnetic force acting on the susceptibility gradient (fsc) was examined by three
dimensional numerical computations. Thermal convection of water enclosed in a
shallow cylindrical vessel (diameter over vessel height = 6.0) with the Rayleigh
Benard model was adopted as the model, under the conditions of Prandtl number 6.0
and Ra number 7000, respectively. The momentum equations of convection were
nondimensionalized, which involved the term of fsc and the term of magnetic force
acting on the magnetic field gradient (fb). All the computations resulted in
axisymmetric steady rolls. The values of the averaged Nu, the averaged velocity
components U, V, and W, and the isothermal distributions and flow patterns were
almost completely the same, regardless of the presence or absence of the term of
fsc. As a result, we found that the effect of fsc was extremely small, although
much previous research emphasized the effect with paramagnetic solutions under an
unsteady state. The magnitude of fsc depends not only on magnetic conditions
(magnitudes of magnetic susceptibility and magnetic flux density), but also on
the thermal properties of the solution (thermal conductivity, thermal
diffusivity, and viscosity). Therefore the effect of fb becomes dominant on the
magnetothermal convection. Active control over the density gradient with
temperature will be required to advance heat transfer with the effect of fsc.
PMID- 27606825
TI - Once hurt, twice shy: Social pain contributes to social anxiety.
AB - Social rejection has been consistently linked to the development of social
anxiety. However, mechanisms underlying the relation have been largely
unexplored, which presents an obstacle to fully understanding the origins of
social anxiety and to the development of effective prevention and treatment
strategies. Two studies were conducted to test the hypothesis that the emotion of
social pain following rejection promotes the development of social anxiety in
subsequent situations. In Study 1, undergraduate participants were exposed to 2
social situations (Cyberball) 2 days apart. Participants who were rejected in the
first situation reported higher social anxiety before and during the second
situation relative to those who were included. This effect was fully mediated by
initial social pain intensity. In Study 2, all participants were initially
rejected. Using double-blinded drug administration, participants were randomly
assigned to ingest acetaminophen to alleviate the social pain from rejection, or
a sugar placebo. As predicted, the acetaminophen group reported lower social
anxiety before and during the second situation. Approximately half of the effect
was mediated by reduction in social pain. Notably, the immediate effect of
acetaminophen was specific to social pain rather than social anxiety. Results
were discussed in the context of literature on the etiology of social anxiety and
social pain. Future directions were suggested. (PsycINFO Database Record
PMID- 27606826
TI - Contextual influences on concordance between maternal report and laboratory
observation of toddler fear.
AB - Emotion and temperament researchers have faced an enduring issue of how to best
measure children's tendencies to express specific emotions. Inconsistencies
between laboratory observation and parental report have made it challenging for
researchers to determine the utility of these different forms of measurement. The
current study examined the effect of laboratory episode characteristics (i.e.,
threat level of the episode, maternal involvement) on concordance between
maternal report and laboratory observation of toddler fear. The sample included
111 mother-toddler dyads who participated in a laboratory assessment when
toddlers were approximately 24 months old. Toddler fear was assessed both via
maternal report and observation from a number of laboratory episodes that varied
in their level of threat and whether mothers were free or constrained in their
involvement in the task. Results indicated that maternal report related to the
observed fear composites for low threat, but not high threat episodes. On the
contrary, maternal involvement in the laboratory episodes did not moderate the
relation between maternal report and laboratory observation of fear. These
results suggest that the threat level of laboratory episodes designed to elicit
fear, but not maternal involvement in these episodes, may be important to take
into consideration when assessing their relation to maternal report of fear and
fearful temperament. (PsycINFO Database Record
PMID- 27606827
TI - Children's emotion understanding and mother-child attachment: A meta-analysis.
AB - Understanding emotions serves as a critical foundation for several aspects of
children's social development. Secure attachment relationships, which allow for
open emotion communication between the parent and child, are hypothesized to
foster emotion understanding. The goal of the current meta-analysis was to
determine the strength of the relationship between emotion understanding and
attachment security. We conducted an electronic search using PsycINFO and
identified 10 studies (N = 564 children) examining this association in children
younger than 18 years of age. The meta-analysis yielded a medium and significant
overall effect size of r = .33 with no significant moderators. Thus, our results
demonstrated that the association between emotion understanding and security of
attachment is quite robust. (PsycINFO Database Record
PMID- 27606828
TI - Moving threat: Attention and distance change interact in threat responding.
AB - Defensive reactions need to be quick and appropriate to ensure survival. Thus, it
is crucial that threats trigger immediate action upon detection, even in the
absence of awareness. In addition, the form of such action should be appropriate
to the imminence of the threat. Thus, attention should be guided by signals of
increasing threat imminence. We examined whether subliminally presented threat
stimuli provoke automatic avoidance tendencies, and whether threat cues' distance
change and threat potential determine attention allocation. Following fear
conditioning, participants performed an approach-avoidance task with subliminally
presented conditioned threat and safety stimuli, and an attentional bias task
with approaching versus distancing signals of threat and safety. Preattentive
processing of threat cues resulted in approach rather than avoidance tendencies;
attention was captured preferentially by signals of increasing threat imminence.
The results support the importance of threat imminence and extend findings of
previous research on preattentive influences on defensive responding. (PsycINFO
Database Record
PMID- 27606829
TI - LOX Fails to Substitute for RANKL in Osteoclastogenesis.
AB - Osteoclasts are the exclusive bone-resorbing cells that have a central role in
bone homeostasis as well as bone destruction in cancer and autoimmune disease.
Both mouse and human genetic studies have clearly proven that receptor activator
of NF-kappaB ligand (RANKL; encoded by the Tnfsf11 gene) and its receptor RANK
are essential for osteoclastogenesis. Although there have been several reports on
RANKL-independent osteoclastogenesis, previous studies have never provided in
vivo evidence showing RANKL can be substituted by other molecules using RANKL- or
RANK-deficient genetic backgrounds. Thus, to date, there is no clear evidence of
RANKL-independent osteoclastogenesis and no molecule has ever been proven capable
of inducing osteoclast differentiation more efficiently than RANKL. Recently,
lysyl oxidase (LOX), the enzyme that mediates collagen cross-linking, has been
shown to induce human osteoclasts in the absence of RANKL and has a stronger
osteoclastogenic activity than RANKL. Here, we investigated the effect of LOX on
osteoclast differentiation using RANKL- and RANK-deficient cells to strictly
explore RANKL-independent osteoclastogenesis. CD14+ human peripheral blood cells
as well as osteoclast precursor cells derived from wild-type, RANKL- and RANK
deficient mice were treated with RANKL and/or LOX in short-term (3 days) or long
term (3 weeks) experimental settings. LOX treatment alone did not result in the
formation of tartrate-resistant acid phosphatase (TRAP)+ cells or resorption pits
in either short-term or long-term culture. In combination with RANKL, long-term
treatment with LOX synergistically promoted osteoclastogenesis in cells derived
from wild-type mice; however, this was abrogated in RANKL-deficient cells. Long
term treatment with LOX stimulated RANKL expression in mouse bone marrow stromal
cells via the production of reactive oxygen species (ROS). Furthermore, LOX
injection failed to rescue the phenotype of RANKL-deficient mice. These results
suggest that LOX has the ability to induce RANKL expression on stromal cells;
however, it fails to substitute for RANKL in osteoclastogenesis. (c) 2016
American Society for Bone and Mineral Research.
PMID- 27606830
TI - Sustained Release of Antibacterial Lipopeptides from Biodegradable Polymers
against Oral Pathogens.
AB - The development of antibacterial drugs to overcome various pathogenic species,
which inhabit the oral cavity, faces several challenges, such as salivary flow
and enzymatic activity that restrict dosage retention. Owing to their amphipathic
nature, antimicrobial peptides (AMPs) serve as the first line of defense of the
innate immune system. The ability to synthesize different types of AMPs enables
exploitation of their advantages as alternatives to antibiotics. Sustained
release of AMPs incorporated in biodegradable polymers can be advantageous in
maintaining high levels of the peptides. In this study, four potent ultra-short
lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in
two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO)
and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained
release. The lipopeptide and polymer formulations were tested for antibacterial
activity during one week, by turbidometric measurements of bacterial outgrowth,
anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and
XTT colorimetric assays, mode of action by fluorescence-activated cell sorting
(FACS) and release profile by a fluorometric assay. The results show that an
antibacterial and anti-biofilm effect, as well as membrane disruption, can be
achieved by the use of a formulation of lipopeptide incorporated in biodegradable
polymer.
PMID- 27606832
TI - The oral cavity in leprosy: what clinicians need to know.
AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a
bacillus that has a tropism for skin and peripheral nerves. Leprosy treatment is
based on a multidrug therapy established by the World Health Organization in 1982
and, despite its widespread use, Brazil ranks second worldwide in numbers of
cases. Oral involvement in leprosy has been poorly described in the literature,
and few studies have shown that although the bacillus is found in mucosa,
specific leprosy lesions are rare and affect patients with advanced stages of the
disease. This review aimed to assess the literature on oral manifestations in
leprosy and the aspects involving oral cavity in leprosy pathogenesis.
PMID- 27606831
TI - Induced regulatory T cells are phenotypically unstable and do not protect mice
from rapidly progressive glomerulonephritis.
AB - Regulatory T (Treg) cells are a suppressive CD4+ T-cell subset. We generated
induced Treg (iTreg) cells and explored their therapeutic potential in a murine
model of rapidly progressive glomerulonephritis. Polyclonal naive CD4+ T cells
were cultured in vitro with interleukin-2 (IL-2), transforming growth factor
beta1, all-trans-retinoic acid and monoclonal antibodies against interferon-gamma
and IL-4, generating Foxp3+ iTreg cells. To enhance their suppressive phenotype,
iTreg cultures were modified with the addition of a monoclonal antibody against
IL-12p40 or by using RORgammat-/- CD4+ T cells. Induced Treg cells were
transferred into models of delayed-type hypersensitivity and experimental
glomerulonephritis. The iTreg cells exhibited comparable surface receptor
expression and in vitro suppressive ability to natural Treg cells, but did not
regulate antigen-specific delayed-type hypersensitivity or systemic inflammatory
immune responses, losing Foxp3 expression in vivo. In glomerulonephritis,
transferred iTreg cells did not prevent renal injury or modulate systemic T
helper type 1 immune responses. Induced Treg cells cultured with anti-IL-12p40
had an enhanced suppressive phenotype in vitro and regulated dermal delayed-type
hypersensitivity in vivo, but were not protective against renal injury, losing
Foxp3 expression, especially in the transferred cells recruited to the kidney.
Use of RORgammat-/- CD4+ T cells or iTreg cells generated from sensitized CD4+
Foxp3- cells did not regulate renal or systemic inflammatory responses in vivo.
In conclusion, iTreg cells suppress T-cell proliferation in vitro, but do not
regulate experimental glomerulonephritis, being unstable in this inflammatory
milieu in vivo.
PMID- 27606833
TI - Significant difference in active metabolite levels of ginseng in humans consuming
Asian or Western diet: The link with enteric microbiota.
AB - After ingestion of ginseng, the bioavailability of its parent compounds is low
and enteric microbiota plays an important role in parent compound
biotransformation to their metabolites. Diet type can influence the enteric
microbiota profile. When human subjects on different diets ingest ginseng, their
different gut microbiota profiles may influence the metabolism of ginseng parent
compounds. In this study, the effects of different diet type on gut microbiota
metabolism of American ginseng saponins were investigated. We recruited six
healthy adults who regularly consumed different diet types. These subjects
received 7 days' oral American ginseng, and their biological samples were
collected for LC-Q-TOF-MS analysis. We observed significant ginsenoside Rb1 (a
major parent compound) and compound K (a major active metabolite) level
differences in the samples from the subjects consuming different diets. Subjects
on an Asian diet had much higher Rb1 levels but much lower compound K levels
compared with those on a Western diet. Since compound K possesses much better
cancer chemoprevention potential, our data suggested that consumers on a Western
diet should obtain better cancer prevention effects with American ginseng intake
compared with those on an Asian diet. Ginseng compound levels could be enhanced
or reduced via gut microbiota manipulation for clinical utility.
PMID- 27606834
TI - Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via
the PI3K/AKT and MAPK Signaling Pathways.
AB - Prostate cancer is the most common cancer in men and the second most common cause
of cancer-related deaths in men. Although, various drugs targeting the androgen
receptor are normally used, the patients frequently undergo recurrence of the
disease. To overcome these limitations, natural compounds have been researched
for evidence that they suppress progression and metastasis of various cancer
cells. In the present study, we investigated effects of naringenin, a natural
anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and
LNCaP). Results of present study with PC3 and LNCaP cells revealed that
naringenin inhibited proliferation and migration, while inducing apoptosis and
ROS production by those cells. In addition, naringenin-induced loss of
mitochondrial membrane potential and increased Bax and decreased Bcl-2 proteins
in PC3 cells, but not LNCaP cells. In a dose-dependent manner, naringenin
decreased phosphorylation of ERK1/2, P70S6K, S6, and P38 in PC3 cells, and
reduced phosphorylation of ERK1/2, P53, P38, and JNK proteins in LNCaP cells.
However, naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells.
Then, targeted signaling proteins associated with viability of PC3 and LNCaP
cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell
signaling pathways. Moreover, we compared the apoptotic effects of naringenin and
paclitaxel alone and in combination to find that naringenin enhanced the
efficiency of paclitaxel to suppress progression of prostate cancer cell lines.
Collectively, these results indicate that naringenin is a potential
chemotherapeutic agent for treatment of prostate cancer. J. Cell. Biochem. 118:
1118-1131, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27606835
TI - Multidimensional Self-Assembled Structures of Alkylated Cellulose Oligomers
Synthesized via in Vitro Enzymatic Reactions.
AB - The self-assembly of biomolecules into highly ordered nano-to-macroscale
structures is essential in the construction of biological tissues and organs. A
variety of biomolecular assemblies composed of nucleic acids, peptides, and
lipids have been used as molecular building units for self-assembled materials.
However, crystalline polysaccharides have rarely been utilized in self-assembled
materials. In this study, we describe multidimensional self-assembled structures
of alkylated cellulose oligomers synthesized via in vitro enzymatic reactions. We
found that the alkyl chain length drastically affected the assembled morphologies
and allomorphs of cellulose moieties. The modulation of the intermolecular
interactions of cellulose oligomers by alkyl substituents was highly effective at
controlling their assembly into multidimensional structures. This study proposes
a new potential of crystalline oligosaccharides for structural components of
molecular assemblies with controlled morphologies and crystal structures.
PMID- 27606836
TI - Bullectomy: A Waste of Space or Room for Improvement?
PMID- 27606837
TI - Transpulmonary Pressure: The Importance of Precise Definitions and Limiting
Assumptions.
AB - Recent studies applying the principles of respiratory mechanics to respiratory
disease have used inconsistent and mutually exclusive definitions of the term
"transpulmonary pressure." By the traditional definition, transpulmonary pressure
is the pressure across the whole lung, including the intrapulmonary airways,
(i.e., the pressure difference between the opening to the pulmonary airway and
the pleural surface). However, more recently transpulmonary pressure has also
been defined as the pressure across only the lung tissue (i.e., the pressure
difference between the alveolar space and the pleural surface), traditionally
known as the "elastic recoil pressure of the lung." Multiple definitions of the
same term, and failure to recognize their underlying assumptions, have led to
different interpretations of lung physiology and conclusions about appropriate
therapy for patients. It is our view that many current controversies in the
physiological interpretation of disease are caused by the lack of consistency in
the definitions of these common physiological terms. In this article, we discuss
the historical uses of these terms and recent misconceptions that may have
resulted when these terms were confused. These misconceptions include assertions
that normal pleural pressure must be negative (subatmospheric) and that a
pressure in the pleural space may not be substantially positive when a subject is
relaxed with an open airway. We urge specificity and uniformity when using
physiological terms to define the physical state of the lungs, the chest wall,
and the integrated respiratory system.
PMID- 27606838
TI - The Effects of Dalfampridine on Hereditary Spastic Paraparesis.
PMID- 27606839
TI - Subchondral bone changes and the impacts on joint pain and articular cartilage
degeneration in osteoarthritis.
AB - Subchondral bone has received increasing attention in both basic and clinical
research on osteoarthritis (OA). Subchondral bone in OA presents abnormalities in
structure, biochemical composition, biomechanics and cellular function. Overall,
subchondral bone mainly shows bone resorption in early OA and bone formation in
late OA. More and more evidence suggests that abnormalities in subchondral bone
of OA promote joint pain generation and articular cartilage degeneration.
Inhibition or amelioration of subchondral bone abnormalities can reduce joint
pain and can delay cartilage degeneration; thus, subchondral bone-targeted
treatment promises to be a new treatment approach for OA. The pathological
changes and the role of subchondral bone in OA still require further
investigation.
PMID- 27606840
TI - The Structural Architecture of an Infectious Mammalian Prion Using Electron
Cryomicroscopy.
AB - The structure of the infectious prion protein (PrPSc), which is responsible for
Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has
escaped all attempts at elucidation due to its insolubility and propensity to
aggregate. PrPSc replicates by converting the non-infectious, cellular prion
protein (PrPC) into the misfolded, infectious conformer through an unknown
mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate
into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of
these infectious conformers is essential to understanding prion replication and
the development of structure-based therapeutic interventions. Here we used the
repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to
analyze their structure via electron cryomicroscopy. Fourier-transform analyses
of averaged fibril segments indicate a repeating unit of 19.1 A. 3D
reconstructions of these fibrils revealed two distinct protofilaments, and,
together with a molecular volume of 18,990 A3, predicted the height of each PrP
27-30 molecule as ~17.7 A. Together, the data indicate a four-rung beta-solenoid
structure as a key feature for the architecture of infectious mammalian prions.
Furthermore, they allow to formulate a molecular mechanism for the replication of
prions. Knowledge of the prion structure will provide important insights into the
self-propagation mechanisms of protein misfolding.
PMID- 27606880
TI - New method for characterizing electron mediators in microbial systems using a
thin-layer twin-working electrode cell.
AB - Microbial biofilms are significant ecosystems where the existence of redox
gradients drive electron transfer often via soluble electron mediators. This
study describes the use of two interfacing working electrodes (WEs) to simulate
redox gradients within close proximity (250um) for the detection and
quantification of electron mediators. By using a common counter and reference
electrode, the potentials of the two WEs were independently controlled to
maintain a suitable "voltage window", which enabled simultaneous oxidation and
reduction of electron mediators as evidenced by the concurrent anodic and
cathodic currents, respectively. To validate the method, the electrochemical
properties of different mediators (hexacyanoferrate, HCF, riboflavin, RF) were
characterized by stepwise shifting the "voltage window" (ranging between 25 and
200mV) within a range of potentials after steady equilibrium current of both WEs
was established. The resulting differences in electrical currents between the two
WEs were recorded across a defined potential spectrum (between -1V and +0.5V vs.
Ag/AgCl). Results indicated that the technique enabled identification (by the
distinct peak locations at the potential scale) and quantification (by the peak
of current) of the mediators for individual species as well as in an aqueous
mixture. It enabled a precise determination of mid-potentials of the externally
added mediators (HCF, RF) and mediators produced by pyocyanin-producing
Pseudomonas aeruginosa (WACC 91) culture. The twin working electrode described is
particularly suitable for studying mediator-dependent microbial electron transfer
processes or simulating redox gradients as they exist in microbial biofilms.
PMID- 27606881
TI - Raman Study of the Structural Distortion in the Ni1-xCoxTiO3 Solid Solution.
AB - Raman spectra were collected on Ni1-xCoxTiO3 (0 <= x <= 1) ilmenite samples as a
function of the temperature between 4 and 1200 K. An evident symmetry lowering
from the prototype R3 symmetry is observed. The distortion was largest for the x
= 0.40 and 0.50 samples and significantly diminished for small and large values
of x. The distortion was preserved in the whole temperature range and, except for
the x = 0.50 sample, did not show significant changes. Notably, between 25 and 69
K, distortion of the x = 0.40 sample is accompanied by ferromagnetic order. The
direct cation-cation and O-mediated indirect interactions are discussed as
mechanisms behind the distortion and magnetic order. A reversible order-disorder
phase transformation, assigned to occur between the ilmenite and corundum phases,
took place at 973 K in the x = 0.50 sample. Completion of the transformation took
over 1 h. The role of the overlap of Co/Ni and Ti 3d orbitals through O
octahedral faces for charge transfer is discussed.
PMID- 27606879
TI - RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated
Cellular Senescence in OSCC.
AB - RNA-binding proteins (RBP) regulate numerous aspects of co- and post
transcriptional gene expression in cancer cells. Here, we demonstrate that RBP,
fragile X-related protein 1 (FXR1), plays an essential role in cellular
senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1
in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure
within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A,
Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their
turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the
activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and
ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21
mRNA, subsequently reduces p21 protein expression in oral cancer cells. In
addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular
senescence possibly through telomerase activity. Finally, we report that FXR1
regulated senescence is irreversible and FXR1-depleted cells fail to form
colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel
mechanism of controlling the expression of p21 through p53-dependent manner to
bypass cellular senescence in oral cancer cells.
PMID- 27606883
TI - The erbium:YAG Laser: a new technique for the treatment of scrotal calcinosis.
PMID- 27606882
TI - Ouabain Modulates the Distribution of Connexin 43 in Epithelial Cells.
AB - BACKGROUND/AIMS: The fact that ouabain has been identified as an endogenous
substance, led us to inquire its physiological role in epithelial cells. Based on
previous observations, we hypothesized that it influences processes related to
cell contacts. Previously we have shown that nanomolar concentrations of ouabain
up-regulate tight junctions, accelerate ciliogenesis, and increase gap junctional
intercellular communication (GJIC). Given that silencing assays indicated that
connexin 43 (Cnx43) is involved in the GJIC response, in the present work we
study whether ouabain affects Cnx43 expression and distribution. METHODS: We
seeded confluent monolayers of epithelial renal MDCK cells and incubated them
with 10 nM ouabain during 1 h. Then we measured, by densitometric analysis of
Western blot assays, the amount of Cnx43 in cells and in fractions enriched of
plasma membrane. We also studied its localization with immunofluorescence and
confocal microscopy. RESULTS: Cnx43 is remarkably displayed, outlining the
borders of cells gathered in clusters, randomly scattered throughout the
monolayer. Ouabain increases the density of such clusters, as well as the average
number of cells per cluster, without inducing the synthesis of new Cnx43. It also
promotes relocation towards the membrane, of subunits already available. The fact
that such changes are inhibited by PP2 and PD98059 indicates that a signaling
pathway, that includes c-Src and ERK1/2, is involved in this response.
CONCLUSION: Ouabain induces the translocation of Cnx43 from the cytoplasm to the
plasma membrane. These findings support our hypothesis that one of the
physiological roles of ouabain is the modulation of physiological processes that
depend on cell to cell contacts.
PMID- 27606884
TI - Central retinal artery occlusion, an early sign of crizotinib resistance in an
alk positive adenocarcinoma of lung: A rare case report.
AB - About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase
fusion gene and occur almost absolutely in carcinomas arising in non-smokers.
Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c
Met receptor kinase, has been used in the treatment of ALK-positive non-small
cell lung cancer. Side effects of crizotinib mostly consist of grade 1-2
gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2
edema and fatigue; grade 1 visual disorders, rare cases of elevated liver enzymes
and pneumonitis. We are presenting a case of adenocarcinoma of lung, who
progressed on first-line chemotherapy and received crizotinib as second line
therapy for 9 months. Patient has very good partial response to crizotinib and
had some side effects of crizotinib like nausea, vomiting, diarrhea, fatigue,
asthenia and anorexia, asymptomatic transaminitis in the first 2 to 3 weeks of
therapy and managed symptomatically. But after 9 months, he developed sudden
onset left sided vision loss. On fundoscopic examination he was found to have
"cherry red spot" and fundus flourescein angiography revealed central retinal
artery occlusion (CRAO). After 15 days of vision loss patient developed pleural
effusion, and pleural fluid cytology was positive for malignant cells. Visual
symptoms are very well known in the literature as side effects of crizotinib, but
CRAO is not yet been documented. As this patient is not having any prothrombotic
state like diabetes, hypertension, atherosclerosis, hyperhomocysteinemia or any
genetic disorders except malignancy. Hypercoagulability disorders are known to be
commonly associated with a variety of cancer types including lung cancer. This
appears to be a sign of early crizotinib resistance in this patient because there
was no history of prior hypercoagulable state. To the best of our knowledge this
is the first case report in the world literature, as CRAO presenting as a sign of
crizotinib resistance in an adenocarcinoma of lung patient who was on crizotinib.
PMID- 27606885
TI - Discovery and Optimization of 1-Phenoxy-2-aminoindanes as Potent, Selective, and
Orally Bioavailable Inhibitors of the Na+/H+ Exchanger Type 3 (NHE3).
AB - The design, synthesis, and structure-activity relationship of 1-phenoxy-2
aminoindanes as inhibitors of the Na+/H+ exchanger type 3 (NHE3) are described
based on a hit from high-throughput screening (HTS). The chemical optimization
resulted in the discovery of potent, selective, and orally bioavailable NHE3
inhibitors with 13d as best compound, showing high in vitro permeability and
lacking CYP2D6 inhibition as main optimization parameters. Aligning 1-phenoxy-2
aminoindanes onto the X-ray structure of 13d then provided 3D-QSAR models for
NHE3 inhibition capturing guidelines for optimization. These models showed good
correlation coefficients and allowed for activity estimation. In silico ADMET
models for Caco-2 permeability and CYP2D6 inhibition were also successfully
applied for this series. Moreover, docking into the CYP2D6 X-ray structure
provided a reliable alignment for 3D-QSAR models. Finally 13d, renamed as SAR197,
was characterized in vitro and by in vivo pharmacokinetic (PK) and
pharmacological studies to unveil its potential for reduction of obstructive
sleep apneas.
PMID- 27606887
TI - Self-awareness of "Gum Disease" Among US Adults.
AB - BACKGROUND: To assess the extent of self-awareness of gum disease among adults in
the United States. METHODS: Data were from the 2009-2012 National Health and
Nutrition Examination Survey. The outcome variable is self-awareness of gum
disease. Multivariate logistic regression models were used to examine the
relationship between self-awareness and clinically diagnosed periodontitis. The
analytical sample included 6876 participants. RESULTS: Among those participants
(30 years or older) who were classified as having periodontitis, 27% (95%
confidence interval [CI], 24.4-29.8) were self-aware of the disease (positive
predicted value = 25%). Of those who self-reported having gum disease, 14.1% had
a diagnosis of periodontitis (sensitivity = 75%). Older adults were less likely
to be aware of gum disease (P < .05). Non-Hispanic blacks (adjusted odds ratio
[AOR] = 0.67; 95% CI, 0.53-0.85) were less likely to be aware of the disease than
non-Hispanic whites. Adults with diabetes (AOR = 1.61; 95% CI, 1.25-2.06), or
with lung disease (AOR = 1.61; 95% CI, 1.25-2.08), or current smokers (AOR =
1.72; 95% CI, 1.29-2.31) were more likely to be aware of the disease. CONCLUSION:
The study showed that self-awareness of gum disease among adults was low. Our
study findings suggest that there is a great need to improve oral health
knowledge and awareness among the adult population in the United States.
PMID- 27606886
TI - Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats
with Intraplantar Carrageenan-Induced Inflammation.
AB - Previously, we demonstrated intrathecal administration of oxytocin strongly
induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist
(atosiban), the descending oxytocinergic pathway was found to regulate
inflammatory hyperalgesia in our previous study using male rats. The activity of
this neural pathway is elevated during hyperalgesia, but whether this effect
differs in a sex-dependent manner remains unknown. We conducted plantar tests on
adult male and female virgin rats in which paw inflammation was induced using
carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti
hyperalgesic effect in female rats, except at an extremely high dose. Female rats
exhibited similar extent of hyperalgesia to male rats did when the animals
received the same dose of carrageenan. When atosiban was administered alone, the
severity of hyperalgesia was not increased in female rats. Moreover, insulin
regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal
cords of female rats compared with those of male rats. Oxytocin-induced anti
hyperalgesia exhibits a sex-dependent difference in rats. This difference can
partially result from the higher expression of IRAP in the spinal cords of female
rats, because IRAP functions as an enzyme that degrades oxytocin. Our study
confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia
at the spinal level in rats.
PMID- 27606889
TI - Cellular distribution of alkaloids and their translocation via phloem and xylem:
the importance of compartment pH.
AB - The physico-chemical background of alkaloid allocation within plants is outlined
and discussed exemplarily for pyrrolizidine alkaloids (PAs) and nicotine. The
trigger for this discourse is the finding that, for example, PAs, which are taken
up from the soil, are translocated in the xylem, whereas - when genuinely present
in plants - they are allocated as N-oxides via phloem. Special emphasis is put on
the impact of different pH values in certain compartments, as this entails
significant changes in the relative lipophilic character of alkaloids: tertiary
alkaloids diffuse readily through biomembranes, while the corresponding
protonated alkaloids are retained in acidic compartments, i.e. vacuoles or xylem.
Therefore, this phenomenon, well known as the 'ion trap mechanism', is also
relevant for long-distance transport of alkaloids. Any efficient allocation of
typical tertiary alkaloids within the phloem can thus be excluded. In contrast,
due to their strongly increased hydrophilic properties, alkaloid-N-oxides or
quarternary alkaloids cannot diffuse through biomembranes and, consequently,
would be retained in the acidic xylem during translocation. The major aim of this
paper is to sharpen the mind for the chemical peculiarities of alkaloids and to
consider them adequately in forthcoming investigations on allocation of
alkaloids.
PMID- 27606888
TI - A global study of the unmet need for glycemic control and predictor factors among
patients with type 2 diabetes mellitus who have achieved optimal fasting plasma
glucose control on basal insulin.
AB - BACKGROUND: This study used data from different sources to identify the extent of
the unmet need for postprandial glycemic control in patients with type 2 diabetes
mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia
Pacific, the United States, and Latin America. METHODS: Different levels of
evidence were used as available for each country/region, with data extracted from
seven randomized controlled trials (RCTs), three clinical trial registries
(CTRs), and three electronic medical record (EMR) databases. Glycemic status was
categorized as "well controlled" (glycated hemoglobin [HbA1c ] at target [<7%]),
"residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA1c at target
[FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific
recommendations]), or "uncontrolled" (both FPG and HbA1c above target). Predictor
factors were identified from the RCT data set using logistic regression analysis.
RESULTS: RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1%
of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and
uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8%
to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to
21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of
residual hyperglycemia identified from RCT data included high baseline HbA1c (all
countries/regions except Brazil), high baseline FPG (United Kingdom/Japan),
longer duration of diabetes (Brazil), and female sex (Europe/Latin America).
CONCLUSIONS: Irrespective of intrinsic differences between data sources, 24% to
54% of patients with T2DM globally had residual hyperglycemia with HbA1c not at
target, despite achieving FPG control, indicating a significant unmet need for
postprandial glycemic control.
PMID- 27606891
TI - Angioedema associated with excessive sweating and sweat allergy.
PMID- 27606890
TI - Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis.
AB - OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine
protease that regulates cholesterol metabolism through low-density lipoprotein
receptor degradation and that has been linked with cardiovascular risk. The
purpose of the present study was to examine whether PCSK9 levels are related to
both abnormalities in the lipid profile and the severe atherosclerosis that occur
in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study that
encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched
controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and
carotid intima-media thickness (cIMT) and carotid plaques were assessed in
patients and controls. A multivariable analysis, adjusted for standard
cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on
RA related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: After
adjusting for classical cardiovascular risk factors, lipid profile and statins,
RA patients showed lower PCSK9 serum concentrations than controls (beta
coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both
cIMT and the presence of carotid plaques in RA patients. However, this
association was lost after adjusting for classical cardiovascular risk factors.
CONCLUSIONS: PCSK9 is down-regulated in patients with RA.
PMID- 27606892
TI - Inhibition of major integrin alphaV beta3 reduces Staphylococcus aureus
attachment to sheared human endothelial cells.
AB - : Essentials Staphylococcus aureus (S. aureus) binds and impairs function of
vascular endothelial cells (EC). We investigated the molecular signals triggered
by S. aureus adhesion to EC. Inhibition of the EC integrin alphaVbeta3 reduces S.
aureus binding and rescues EC function. alphaVbeta3 blockade represents an
attractive target to treat S. aureus bloodborne infections. SUMMARY: Background
Vascular endothelial dysfunction with associated edema and organ failure is one
of the hallmarks of sepsis. Although a large number of microorganisms can cause
sepsis, Staphylococcus aureus (S. aureus) is one of the primary etiologic agents.
Currently, there are no approved specific treatments for sepsis, and the initial
management bundle is therefore focused on cardiorespiratory resuscitation and
mitigation of the immediate threat of uncontrolled infection. The continuous
emergence of antibiotic-resistant strains of bacteria necessitates the
development of new therapeutic approaches for this disease. Objective To identify
the molecular mechanisms leading to endothelial dysfunction as a result of S.
aureus binding. METHODS: Binding of wild type and Clumping factor A (ClfA)
deficient S. aureus Newman to the endothelium was measured in vitro and in the
mesenteric circulation of C57Bl/6 mice. The effects of the alphaV beta3 blocker
cilengitide-on bacterial binding, endothelial VE-cadherin expression, apoptosis,
proliferation and permeability were assessed. Results The major S. aureus cell
wall protein ClfA bound to endothelial cell alphaV beta3 in the presence of
fibrinogen. This interaction resulted in disturbances in barrier function
mediated by VE-cadherin in endothelial cell monolayers, and ultimately cell death
by apoptosis. With a low concentration of cilengitide, ClfA binding to alphaV
beta3 was significantly inhibited both in vitro and in vivo. Moreover, preventing
S. aureus from attaching to alphaV beta3 resulted in a significant reduction in
endothelial dysfunction following infection. Conclusion Inhibition of S. aureus
ClfA binding to endothelial cell alphaV beta3 by cilengitide prevents endothelial
dysfunction.
PMID- 27606893
TI - Management Controversies in Head and Neck Melanoma: A Systematic Review.
AB - Importance: Head and neck melanoma is one of the leading causes of death in the
United States and is currently increasing in prevalence. While there is a
tremendous amount of research published on melanoma, the actual evidence for
complex clinical decision-making can be difficult to interpret and to stay up-to
date on current clinical standards. Objective: To address, in a systematic and
evidence-based approach, the most common clinical controversies with regard to
the workup and management of head and neck melanoma. Evidence Review: A PubMed
and Medline search was performed of the entire English literature with respect to
head and neck melanoma. Priority of review was given to those studies with higher
quality levels of evidence. Findings: Main topics reviewed in this article
include workup for new melanoma, surgical treatment of the primary site, surgical
treatment of the neck, adjuvant radiation therapy, and systemic therapy. Levels
of evidence are used for each controversial clinical question to help the
clinician understand the reliability of the current evidence when making complex
clinical decisions for melanoma management of the head and neck. However, much of
the work done in melanoma, particularly large randomized clinical trials,
includes many other regions of the body. Therefore, these data must be
interpreted in light of the potential differences in clinical behavior and
draining lymphatics between trunk, limbs, and head and neck subsites. Conclusions
and Relevance: The management of head and neck melanoma requires a
multidisciplinary approach, particularly for advanced-stage disease. An in-depth
knowledge of the current evidence available will help guide the surgeon in the
management of this difficult disease.
PMID- 27606894
TI - Hepatitis B Virus X Protein Modulates Apoptosis in NRK-52E Cells and Activates
Fas/FasL Through the MLK3-MKK7-JNK3 Signaling Pathway.
AB - BACKGROUND/AIMS: The hepatitis B virus X protein (HBx) contributes to HBV-induced
injury of renal tubular cells and induces apoptosis via Fas/FasL up-regulation.
However, the mechanism of Fas/FasL activation is unknown. Recent studies
indicated that HBx induction of apoptosis in hepatic cells depends on activating
the MLK3-MKK7-JNKs signaling module, which then up-regulates FasL expression. In
this study, we used NRK-52E cells transfected an HBx expression vector to examine
the role of the MLK3-MKK7-JNKs signaling pathway on HBx-induced renal tubular
cell injury. METHODS: NRK-52E cells were transfected with pc-DNA3.1(+)-HBx to
establish an HBx over-expression model, and with pc-DNA3.1(+)-HBx and
pSilencer3.1-shHBx to establish an HBx low expression model. One control group
was not transfected and another control group was transfected with an empty
plasmid. Cell proliferation was determined by the formazan dye method (Cell
Counting Kit-8) and apoptosis was measured by flow cytometry and fluorescence
microscopy. Western blotting was used to measure the expression of Fas, FasL, and
MLK3-MKK7-JNKs signaling pathway-related proteins. The activity of caspase-8 was
measured by spectrophotometry. RESULTS: Transfection of NRK-52E cells with pc
DNA3.1(+)-HBx inhibited cell proliferation and increased apoptosis and caspase-8
activity. The expression of Fas, FasL, and MLK3-MKK7-JNKs signaling pathway
related proteins were also greater in the pc-DNA3.1(+)-HBx group, but lower in
RNAi group. Furthermore, the activity of MLK3-MKK7-JNKs signaling pathway,
expression of Fas/FasL, and apoptosis were significantly lower in the pc
DNA3.1(+)-HBx group when treated with K252a, a known inhibitor of MLK3.
CONCLUSIONS: Our results show that HBx induces apoptosis in NRK-52E cells and
activates Fas/FasL via the MLK3-MKK7-JNK3-c-Jun signaling pathway.
PMID- 27606895
TI - Chronic Sinusitis and Risk of Head and Neck Cancer in the US Elderly Population.
AB - Importance: Chronic sinusitis may be involved in the etiology of certain head and
neck cancers (HNCs), due to immunodeficiency or inflammation. However, the risk
of specific HNCs among people with chronic sinusitis is largely unknown.
Objective: To evaluate the associations of chronic sinusitis with subsequent HNC,
including nasopharyngeal cancer (NPC), human papillomavirus-related oropharyngeal
cancer (HPV-OPC), and nasal cavity and paranasal sinus cancer (NCPSC), in an
elderly US population. Design, Setting, and Participants: We used the
Surveillance, Epidemiology, and End Results (SEER)-Medicare database to conduct a
case-cohort study of US individuals aged 65 years or older during 2004 through
2011. The study included 483 546 Medicare beneficiaries from SEER areas in a 5%
random subcohort, and 826 436 from the entire source population who developed
cancer (including 21 716 with HNC). Main Outcomes and Measures: Incidence of HNCs
including NPC, HPV-OPC, and NCPSC. Results: Most individuals were female (57.7%),
and the mean (SD) age at entry was 72.6 (8.0) years. Chronic sinusitis was
associated with risk of developing HNC (adjusted hazard ratio [aHR], 1.37; 95%
CI, 1.27-1.48), particularly NPC (aHR, 3.71; 95% CI, 2.75-5.02), HPV-OPC (aHR,
1.33; 95% CI, 1.13-1.57), and NCPSC (aHR, 5.49; 95% CI, 4.56-6.62). Most of this
increased risk was limited to risk within 1 year of the chronic sinusitis
diagnosis, as associations were largely attenuated 1 year or more after chronic
sinusitis (NPC: aHR, 1.60; 95% CI, 0.96-2.65; HPV-OPC: aHR, 1.07; 95% CI, 0.86
1.32; NCPSC: aHR, 2.47; 95% CI, 1.84-3.31). All 3 HNC subtypes had cumulative
incidence of less than 0.07% 8 years after chronic sinusitis diagnosis.
Conclusions and Relevance: Chronic sinusitis is associated with certain HNCs,
particularly NPC and NCPSC. These HNCs are rare, and most of the increased HNC
risk is limited to within 1 year of chronic sinusitis diagnosis, consistent with
surveillance or detection bias. The associations were weaker over longer
intervals, suggesting at most a modest role for sinusitis-related inflammation
and/or immunodeficiency.
PMID- 27606896
TI - Synthesis of Disubstituted 3-Phenylimidazo[1,2-a]pyridines via a 2
Aminopyridine/CBrCl3 alpha-Bromination Shuttle.
AB - A versatile protocol for the synthesis of disubstituted 3-phenylimidazo[1,2
a]pyridines by coupling 2-aminopyridine with phenylacetophenones, phenylacetones,
or beta-tetralone has been developed. Isolated yields of up to 97% were obtained
at 80 degrees C within 5 h. The 2-aminopyridine/CBrCl3 system acts as an alpha
bromination shuttle by transferring Br from CBrCl3 to the alpha-carbon of the
carbonyl moiety. This triggers a series of steps with double C-N/C-N bond
formation to the final product. The distinct advantages of this protocol include
the use of commercially available inexpensive substrates, simplicity of a metal
free one-pot synthesis, and ease of scale-up to multigram quantities.
PMID- 27606897
TI - Secure Base Priming Diminishes Conflict-Based Anger and Anxiety.
AB - This study examines the impact of a visual representation of a secure base (i.e.
a secure base prime) on attenuating experimentally produced anger and anxiety.
Specifically, we examined the assuaging of negative emotions through exposure to
an image of a mother-infant embrace or a heterosexual couple embracing. Subjects
seated at a computer terminal rated their affect (Pre Affect) using the Affect
Adjective Checklist (AAC) then listened to two sets of intense two person
conflicts. After the first conflict exposure they rated affect again (Post 1
AAC). Following the second exposure they saw a blank screen (control condition),
pictures of everyday objects (distraction condition) or a photo of two people
embracing (Secure Base Prime condition). They then reported emotions using the
Post 2 AAC. Compared to either control or distraction subjects, Secure Base Prime
(SBP) subjects reported significantly less anger and anxiety. These results were
then replicated using an internet sample with control, SBP and two new controls:
Smiling Man (to control for expression of positive affect) and Cold Mother (an
unsmiling mother with infant). The SBP amelioration of anger and anxiety was
replicated with the internet sample. No control groups produced this effect,
which was generated only by a combination of positive affect in a physically
embracing dyad. The results are discussed in terms of attachment theory and
research on spreading activation.
PMID- 27606899
TI - Three-Dimensional Soft Material Micropatterning via Direct Laser Lithography of
Flexible Molds.
AB - Three-dimensionally micropatterned surfaces are attracting increasing interest in
soft robotics owing to the potential of mimicking natural morphologies at the
micro/nanoscale. We employ direct laser lithography to fabricate molds with
complex three-dimensional (3D) micrometric features, in a positive photoresist on
flexible substrates, to pattern curved macroscopic soft surfaces with shapes not
achievable with standard methods (e.g., reentrant angles). We present several 3D
intricate microstructures in poly(dimethylsiloxane) (PDMS) and show a soft
cylinder patterned with 3D microstructures with one molding process. Finally, we
deform PDMS-based 3D architectures and show soft microgripping capability,
indicating the potentiality of this approach for future application in soft
robotics.
PMID- 27606898
TI - Correction: Canine-Based Strategies for Prevention and Control of Visceral
Leishmaniasis in Brazil.
AB - [This corrects the article DOI: 10.1371/journal.pone.0160058.].
PMID- 27606900
TI - Do Hospitalized Premature Infants Benefit from Music Interventions? A Systematic
Review of Randomized Controlled Trials.
AB - OBJECTIVE: Neonatal intensive care units (NICU) around the world increasingly use
music interventions. The most recent systematic review of randomized controlled
trials (RCT) dates from 2009. Since then, 15 new RCTs have been published. We
provide an updated systematic review on the possible benefits of music
interventions on premature infants' well-being. METHODS: We searched 13
electronic databases and 12 journals from their first available date until August
2016. Included were all RCTs published in English with at least 10 participants
per group, including infants born prematurely and admitted to the NICU.
Interventions were either recorded music interventions or live music therapy
interventions. All control conditions were accepted as long as the effects of the
music intervention could be analysed separately. A meta-analysis was not possible
due to incompleteness and heterogeneity of the data. RESULTS: After removal of
duplicates the searches retrieved 4893 citations, 20 of which fulfilled the
inclusion/exclusion criteria. The 20 included studies encompassed 1128
participants receiving recorded or live music interventions in the NICU between
24 and 40 weeks gestational age. Twenty-six different outcomes were reported
which we classified into three categories: physiological parameters; growth and
feeding; behavioural state, relaxation outcomes and pain. Live music
interventions were shown to improve sleep in three out of the four studies and
heart rate in two out of the four studies. Recorded music improved heart rate in
two out of six studies. Better feeding and sucking outcomes were reported in one
study using live music and in two studies using recorded music. CONCLUSIONS:
Although music interventions show promising results in some studies, the
variation in quality of the studies, age groups, outcome measures and timing of
the interventions across the studies makes it difficult to draw strong
conclusions on the effects of music in premature infants.
PMID- 27606902
TI - A new class of fast-response and highly selective fluorescent probes for
visualizing peroxynitrite in live cells, subcellular organelles, and kidney
tissue of diabetic rats.
AB - Peroxynitrite (ONOO(-)) is an extremely powerful oxidant in biological systems,
and can react with a wide variety of molecular targets including proteins,
lipids, and nucleic acids, eventually resulting in a series of disease states
such as diabetes, Alzheimer's disease, cancer, arthritis, autoimmune, and other
disorders. In this work, we present a new class of ONOO(-) fluorescent probes by
exploiting the ONOO(-)-triggered N-oxidation and N-nitrosation reactions of
aromatic tertiary amine for the first time. The as-obtained fluorescent probe A2
could detect ONOO(-) with quite fast fluorescence off-on response (within
seconds), ultrasensitivity (detection limit: <2 nM), and excellent selectivity
over a series of biologically relevant reactive oxygen species as well as metal
cations. With the probe, the endogenous ONOO(-) in activated RAW264.7 murine
macrophage, EA.hy926 endothelial cells after oxygen glucose deprivation and
reoxygenation (OGD/RO), and kidney tissue of diabetic rats has been successfully
visualized. Based on the molecular platform of A2, we further develop its
mitochondria- and lysosome-targetable fluorescent probes Mito-A2 and Lyso-A2 by
installing the corresponding targeting groups to alkoxy unit of A2, and confirm
their abilities to image ONOO(-) in mitochondria and lysosomes, respectively, by
co-localization assays. It is greatly expected that these probes can serve as
useful imaging tools for clarifying the distribution and pathophysiological
functions of ONOO(-) in cells, subcellular organelles, and animal tissues.
PMID- 27606901
TI - 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with
Postinfarction Left Ventricular Remodeling in Response to Cell Therapy.
AB - Utilizing a fast 31P magnetic resonance spectroscopy (MRS) 2-dimensional chemical
shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine
kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV)
remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham
operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior
descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch
group; ligation injury plus open fibrin patch over the site of injury (Patch, n =
6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth
muscle cells (2 million, each) were injected into the injured myocardium pass
through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate
(PCr)/ATP ratio, CK forward flux rate (Flux PCr->ATP), and k constant of CK
forward flux rate (kPCr->ATP) were severely decreased at border zone myocardium
(BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP
ratio and improve the value of kPCr->ATP and Flux PCr->ATP in BZ myocardium.
Moreover, the BZ myocardial CK total activity and protein expression of CK
mitochondria isozyme and CK myocardial isozyme were significantly reduced, but
recovered in response to cell treatment. Thus, cell therapy results in
improvement of BZ bioenergetic abnormality in hearts with postinfarction LV
remodeling, which is accompanied by significantly improvements in BZ CK activity
and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure
the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.
PMID- 27606903
TI - Substance-Treatment Professionals' Perceived Barriers to Incorporating
Mindfulness Into Treatment.
AB - BACKGROUND: Despite scientific favor, psychological interventions supported by
research are often underutilized by practitioners due to perceived obstacles in
implementation. Increased transparency between researchers and practitioners
throughout treatment development and dissemination is therefore necessary. The
rising popularity of mindfulness-based approaches in the treatment of substance
use disorders suggests such transparency is necessary in further developing,
disseminating, and implementing such approaches within the context of substance
treatment. OBJECTIVES: The present study aimed to increase transparency by
surveying substance-treatment professionals regarding their perceptions of
barriers to adopting mindfulness in the treatment of substance use. METHODS:
Substance-treatment professionals throughout the United States (N = 103)
completed an online survey about their perceptions of potential barriers to
implementing mindfulness into substance treatment. RESULTS: Overall,
professionals were moderately familiar with mindfulness as a treatment for
substance use. Approximately one-third reported providing mindfulness in
substance treatment; however, only 7% reported providing mindfulness using a
research-supported treatment manual. Across professionals of various backgrounds,
the need for further training was rated as the greatest barrier to
implementation. CONCLUSIONS/IMPORTANCE: Results suggest that practitioners are
generally familiar with and willing to implement mindfulness in the treatment of
substance use. Future research and implementation efforts should focus on methods
of increasing training availability, accessibility, and relevance to address the
needs and expectations of substance-treatment professionals.
PMID- 27606904
TI - Inhibitory effect of polyunsaturated aldehydes (PUAs) on the growth of the toxic
benthic dinoflagellate Ostreopsis cf. ovata.
AB - Diatoms have been shown to produce and release a wide range of secondary
metabolites that mediate interactions between individuals of different species.
Among these compounds, different types of fatty acid derived long-chained
polyunsaturated aldehydes (PUAs) have been related to multiple functions such as
intra- or interspecific signals and adverse effect on the reproduction of marine
organisms. Several studies have reported changes on growth, cell membrane
permeability, flow cytometric properties and cell morphology in phytoplankton
organisms exposed to PUAs, but little information is available on the effect of
these compounds on benthic microalgae. Ostreopsis cf. ovata is a toxic benthic
dinoflagellate which causes massive blooms along the Mediterranean coasts
typically during the late summer period. In this study the effects of three toxic
PUAs known to be produced by several algae (2E,4E-decadienal, 2E,4E-octadienal
and 2E,4E-heptadienal) on the growth, cytological features and cell morphology of
O. cf. ovata were investigated. Our results show a clear decrease of O. cf. ovata
growth with longer-chain molecules than with shorter-chain ones, confirmed also
by EC50 values calculated at 48h for 2E,4E-decadienal and 2E,4E-octadienal (6.6+/
1.5, 17.9+/-2.6MUmolL(-1) respectively) and at 72h for 2E,4E-heptadienal (18.4+/
0.7MUmolL(-1)). Moreover, morphological analysis highlighted up to 79% of
abnormal forms of O. cf. ovata at the highest concentrations of 2E,4E-decadienal
tested (9, 18 and 36MUmolL(-1)), a gradual DNA degradation and an increase of
lipid droplets with all tested PUAs. Further studies are needed to better clarify
the interactions between diatoms and O. cf. ovata, especially on bloom-forming
dynamics.
PMID- 27606905
TI - Surgical Management of Hiatal Hernia in Children with Asplenia Syndrome.
AB - Purpose Patients with asplenia syndrome (AS) are likely to have upper
gastrointestinal tract malformations such as hiatal hernia. This report discusses
the treatment of such conditions. Methods Seventy-five patients with AS underwent
initial palliation in our institution between 1997 and 2013. Of these, 10
patients had hiatal hernia. Of the patients with hiatal hernia, 6 had
brachyesophagus and 7 had microgastria. Results Of the 10 patients with hiatal
hernia, 9 underwent surgery in infancy (7 before Glenn operation, 2 after Glenn
operation). Two underwent typical Toupet fundoplication, and the other 7
underwent atypical repair including reduction of the stomach. Two patients with
atypical repair showed recurrence of hernia and required reoperation. Three
patients required reoperation due to duodenal obstruction. Duodenal obstruction
occurred due to preduodenal portal vein or abnormal vessels compressing the
duodenum. Obstructive symptoms were not seen in any cases preoperatively.
Conclusions In patients with hiatal hernia, typical fundoplication is often
difficult because most have concomitant brachyesophagus, microgastria, and
hypoplasia of the esophageal hiatus. However, we should at least reduce the
stomach to the abdominal cavity as early as possible to increase thoracic cavity
volume and allow good feeding. Increasing the volume of the thoracic cavity thus
makes Glenn and Fontan circulations more stable. Duodenal obstruction secondary
to vascular anomalies is also common, so the anatomy in the area near the
duodenum should be evaluated pre- and intraoperatively.
PMID- 27606906
TI - Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and
Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with
Cryptorchidism Vanish after the Age of 2 Years.
AB - Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to
testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers
may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism,
because positive immunohistochemistry is commonly seen in boys younger than the
age of 2 years, where most orchiopexies are performed. The aim of the study was
to evaluate the diagnostic challenge to differentiate between a histological
pattern of ITGCN and a histological pattern with some atypical germ cells and all
positive cancer immunohistochemical markers, but no increased risk of malignancy.
Materials and Methods Histology sections from 373 testicular biopsies from 289
boys aged 1 month to 2 years operated for cryptorchidism were incubated with
primary antibodies including anti-placental-like-alkaline phosphatase, antiOct
3/4, anti-C-kit, anti-D2-40, and in case of repeat biopsy with anti-stem cell
factor (SCF) receptor. Results The prevalence of Oct-3/4 and D2-40-positive
staining of germ cells in testicular biopsies were in age groups less than 6
months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1
year, 1-month-old boy with Prader-Willi syndrome treated with growth hormone had
ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases,
8 months, 8 months and 1-year-old, a histological pattern in accordance with
ITGCN was found. These three boys had a repeat biopsy from both testes performed
at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively.
In all cases, the Oct-3/4 and D2-40 positive germ cells turned negative and the
histological pattern normalized completely. The primary biopsies had SCF negative
germ cells. Conclusion This study is valuable in identifying the age-related
change in Oct-3/4 or D2-40 immunopositive germ cells in seminiferous tubules. An
ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after
the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN
is so rarely demonstrated in cryptorchid testes, that it is not plausible that
ITGCN generally originates during fetal development in cryptorchidism.
PMID- 27606908
TI - Pulmonary vein duality: A new encounter with an old friend.
PMID- 27606907
TI - Statistical methods for analyzing ancient DNA from hominins.
AB - In the past few years, the number of autosomal DNA sequences from human fossils
has grown explosively and numerous partial or complete sequences are available
from our closest relatives, Neanderthal and Denisovans. I review commonly used
statistical methods applied to these sequences. These methods fall into three
broad classes: methods for estimating levels of contamination, descriptive
methods, and methods based on population genetic models. The latter two classes
are largely methods developed for the analysis of present-day genomic data. When
they are applied to ancient DNA (aDNA), they usually ignore the time dimension. A
few methods, particularly those concerned with inferring something about
selection or ancestor-descendant relationships, take explicit account of the ages
of aDNA samples.
PMID- 27606909
TI - Pathophysiological mechanisms of noncardiac syncope in athletes.
AB - OBJECTIVE: The investigation of the differences in orthostatic responses of
individuals with a history of noncardiac syncope(NCS) between athletes and
nonathletes. METHODS: A passive tilt test for 30min was performed in 133 athletes
(54 with NCS, 79 without NCS) and 48 nonathletes (15 with NCS, 33 without NCS).
We performed measurement of haemodynamic, heart rate variability and baroreflex
sensitivity parameters. All comparisons were adjusted for age, gender and body
mass index(BMI). RESULTS: Athletes with NCS had increased heart rate(HR) (90+/-11
vs 81+/-10bpm, p=0.001) and decreased total peripheral resistance index(TPRI)
(2227+/-408 vs 2918+/-733dynesm2/cm5, p=0.039) and baroreflex effectiveness
index(BEI) [70.16(37.42-89.71) vs 72.19(48.49-91.35)%, p=0.016] compared with
athletes without NCS. After applying backward stepwise logistic regression
analysis to predict history of NCS in athletes, the final model included age,
gender, BMI, HR and TPRI. Nonathletes with NCS had increased HR (95+/-24 vs 83+/
11bpm, p=0.024) and TPRI (3744+/-1606 vs 2937+/-880dynesm2/cm5, p=0.030) and
decreased stroke index(SI) (25.4+/-7.6 vs 33.0+/-7.5mL/m2, p=0.003) compared with
nonathletes without NCS. After applying backward stepwise logistic regression
analysis to predict history of NCS in nonathletes, the final model included SI
and HR. Among individuals with NCS, athletes had increased SI and BEI and
decreased HR and TPRI compared with nonathletes. Among individuals without NCS, a
positive result of tilt test was less frequent in athletes compared with
nonathletes (p=0.031). CONCLUSIONS: The possible main underlying mechanism for
NCS during upright standing in athletes is the decreased TPRI, while the
inadequate preservation of SI in nonathletes.
PMID- 27606910
TI - [Not Available].
PMID- 27606911
TI - [Not Available].
PMID- 27606912
TI - [Not Available].
PMID- 27606913
TI - [Not Available].
PMID- 27606914
TI - [Not Available].
PMID- 27606915
TI - [Not Available].
PMID- 27606916
TI - [Not Available].
PMID- 27606917
TI - [Not Available].
PMID- 27606918
TI - [Not Available].
PMID- 27606919
TI - [Not Available].
PMID- 27606920
TI - [Not Available].
PMID- 27606921
TI - [Not Available].
PMID- 27606922
TI - [Not Available].
PMID- 27606923
TI - [Not Available].
PMID- 27606924
TI - [Not Available].
PMID- 27606925
TI - Stereoselective determination of citalopram and desmethylcitalopram in human
plasma and breast milk by liquid chromatography tandem mass spectrometry.
AB - A high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS)
method was developed for the simultaneous, stereoselective quantification of the
antidepressant citalopram and its active metabolite desmethylcitalopram in human
plasma and breast milk. Sample preparation was performed by a two-step approach,
including generic protein precipitation with acetonitrile followed by solid phase
extraction. Enantiospecific separation of analytes was achieved on a
Phenomenex(r) Lux Cellulose-2 column (4.6mm*150mm; 5MUm), using reversed phase
chromatography conditions characterized by a gradient elution of ammonium acetate
buffer (pH 9.0; 20mM) and acetonitrile at a flow rate of 0.6ml/min. The compounds
were detected by a tandem quadrupole mass spectrometer equipped with an
electrospray ionization source and operating in multiple reaction monitoring
mode. The method was fully validated in both biological fluids over a large
concentration range of 0.1-100ng/ml for S-(+)- and R-(-)-citalopram, and 0.3
100ng/ml for S-(+)- and R-(-)-desmethylcitalopram. Trueness (90.0-113.3% and 97.1
103.6%), repeatability (0.9-15.9% and 0.9-8.4%) and intermediate precision (1.3
17.8% and 0.9-9.6%) in plasma and breast milk, respectively, meet international
guidelines for method validation. Internal standard-normalized matrix effects
ranged between 99 and 101% and 98-105%, respectively. The accuracy profiles
(total error of trueness and precision) were mostly within the acceptance limits
for biological samples defined as +/-30%. The method was successfully applied to
patient samples in a clinical trial setting.
PMID- 27606926
TI - Directed self-assembly of high-chi block copolymer for nano fabrication of bit
patterned media via solvent annealing.
AB - We report the formation of nanoimprint master templates that can be used for the
fabrication of bit patterned media (BPM). The template was formed by directed
self-assembly, with solvent annealing, of a symmetric ABA triblock copolymer to
form perpendicularly oriented lamellae on chemical patterns. We used a high-chi
block copolymer, poly(2-vinyl pyridine)-block-polystyrene-block-poly(2-vinyl
pyridine) to achieve smaller feature sizes than are possible with polystyrene
block-poly(methyl methacrylate). The work shows that triblock copolymers can
provide a large processing window in terms of pitch commensurability. Using block
selective infiltration (atomic layer deposition with sequential long
soaking/purge cycles), an alumina composite with high etch resistance was
specifically incorporated into the polar and hydrophilic P2VP domains.
Subsequently, the surface pattern was successfully transferred into underlying Si
substrates by etching with a fluorine-containing plasma to create a nanoimprint
master. The line/space pattern of the nanoimprint master met the BPM fabrication
requirement of defectivity <10(-3). For demonstration purposes, the nanoimprint
master was used to imprint a replica pattern of photoresist on a quartz wafer.
PMID- 27606927
TI - Ultra-portable, wireless smartphone spectrometer for rapid, non-destructive
testing of fruit ripeness.
AB - We demonstrate a smartphone based spectrometer design that is standalone and
supported on a wireless platform. The device is inherently low-cost and the power
consumption is minimal making it portable to carry out a range of studies in the
field. All essential components of the device like the light source,
spectrometer, filters, microcontroller and wireless circuits have been assembled
in a housing of dimensions 88 mm * 37 mm * 22 mm and the entire device weighs 48
g. The resolution of the spectrometer is 15 nm, delivering accurate and
repeatable measurements. The device has a dedicated app interface on the
smartphone to communicate, receive, plot and analyze spectral data. The
performance of the smartphone spectrometer is comparable to existing bench-top
spectrometers in terms of stability and wavelength resolution. Validations of the
device were carried out by demonstrating non-destructive ripeness testing in
fruit samples. Ultra-Violet (UV) fluorescence from Chlorophyll present in the
skin was measured across various apple varieties during the ripening process and
correlated with destructive firmness tests. A satisfactory agreement was observed
between ripeness and fluorescence signals. This demonstration is a step towards
possible consumer, bio-sensing and diagnostic applications that can be carried
out in a rapid manner.
PMID- 27606928
TI - Dwarfing Genes Rht-B1b and Rht-D1b Are Associated with Both Type I FHB
Susceptibility and Low Anther Extrusion in Two Bread Wheat Populations.
AB - It has been well documented that dwarfing genes Rht-B1b and Rht-D1b are
associated with Type I susceptibility to Fusarium head blight (FHB) in wheat; but
the underlying mechanism has not been well delineated. Anther extrusion (AE) has
also been related to Type I resistance for initial FHB infection, where high AE
renders FHB resistance. In this study, two doubled haploid populations were used
to investigate the impact of the two dwarfing genes on FHB resistance and AE, and
to elucidate the role of AE in Rht-mediated FHB susceptibility. Both populations
were derived by crossing the FHB susceptible cultivar 'Ocoroni F86' (Rht-B1a/Rht
D1b) with an FHB resistant variety (Rht-B1b/Rht-D1a), which was
'TRAP#1/BOW//Taigu derivative' in one population (the TO population) and
'Ivan/Soru#2' in the other (the IO population). Field experiments were carried
out from 2010 to 2012 in El Batan, Mexico, where spray inoculation was adopted
and FHB index, plant height (PH), and AE were evaluated, with the latter two
traits showing always significantly negative correlations with FHB severity. The
populations were genotyped with the DArTseq GBS platform, the two dwarfing genes
and a few SSRs for QTL analysis, and the results indicated that Rht-B1b and Rht
D1b collectively accounted for 0-41% of FHB susceptibility and 13-23% of reduced
AE. It was also observed that three out of the four AE QTL in the TO population
and four out of the five AE QTL in the IO population were associated with FHB
resistance. Collectively, our results demonstrated the effects of Rht-B1b and Rht
D1b on Type I FHB susceptibility and reducing AE, and proposed that their impacts
on Type I FHB susceptibility may partly be explained by their effects on reducing
AE. The implication of the relationship between the two dwarfing genes and AE for
hybrid wheat breeding was also discussed.
PMID- 27606930
TI - Reference Values for Noninvasive Blood Pressure in Children during Anesthesia: A
Multicentered Retrospective Observational Cohort Study.
AB - BACKGROUND: Although noninvasive blood pressure (NIBP) monitoring during
anesthesia is a standard of care, reference ranges for blood pressure in
anesthetized children are not available. We developed sex- and age-specific
reference ranges for NIBP in children during anesthesia and surgery. METHODS: In
this retrospective observational cohort study, we included NIBP data of children
with no or mild comorbidity younger than 18 yr old from the Multicenter
Perioperative Outcomes Group data set. Sex-specific percentiles of the NIBP
values for age were developed and extrapolated into diagrams and reference tables
representing the 50th percentile (0 SD), +1 SD, -1 SD, and the upper (+2 SD) and
lower reference ranges (-2 SD). RESULTS: In total, 116,362 cases from 10 centers
were available for the construction of NIBP age- and sex-specific reference
curves. The 0 SD of the mean NIBP during anesthesia varied from 33 mmHg at birth
to 67 mmHg at 18 yr. The low cutoff NIBP (2 SD below the 50th percentile) varied
from 17 mmHg at birth to 47 mmHg at 18 yr old. CONCLUSIONS: This is the first
study to present reference ranges for blood pressure in children during
anesthesia. These reference ranges based on the variation of values obtained in
daily care in children during anesthesia could be used for rapid screening of
changes in blood pressure during anesthesia and may provide a consistent
reference for future blood pressure-related pediatric anesthesia research.
PMID- 27606931
TI - Redesign of the System for Evaluation of Teaching Qualities in Anesthesiology
Residency Training (SETQ Smart).
AB - BACKGROUND: Given the increasing international recognition of clinical teaching
as a competency and regulation of residency training, evaluation of
anesthesiology faculty teaching is needed. The System for Evaluating Teaching
Qualities (SETQ) Smart questionnaires were developed for assessing teaching
performance of faculty in residency training programs in different countries.
This study investigated (1) the structure, (2) the psychometric qualities of the
new tools, and (3) the number of residents' evaluations needed per anesthesiology
faculty to use the instruments reliably. METHODS: Two SETQ Smart questionnaires
for faculty self-evaluation and for resident evaluation of faculty-were
developed. A multicenter survey was conducted among 399 anesthesiology faculty
and 430 residents in six countries. Statistical analyses included exploratory
factor analysis, reliability analysis using Cronbach alpha, item-total scale
correlations, interscale correlations, comparison of composite scales to global
ratings, and generalizability analysis to assess residents' evaluations needed
per faculty. RESULTS: In total, 240 residents completed 1,622 evaluations of 247
faculty. The SETQ Smart questionnaires revealed six teaching qualities consisting
of 25 items. Cronbach alpha's were very high (greater than 0.95) for the overall
SETQ Smart questionnaires and high (greater than 0.80) for the separate teaching
qualities. Interscale correlations were all within the acceptable range of
moderate correlation. Overall, questionnaire and scale scores correlated
moderately to highly with the global ratings. For reliable feedback to individual
faculty, three to five resident evaluations are needed. CONCLUSIONS: The first
internationally piloted questionnaires for evaluating individual anesthesiology
faculty teaching performance can be reliably, validly, and feasibly used for
formative purposes in residency training.
PMID- 27606929
TI - Rapporteur summaries of plenary, symposia, and oral sessions from the XXIIIrd
World Congress of Psychiatric Genetics Meeting in Toronto, Canada, 16-20 October
2015.
AB - The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the
International Society of Psychiatric Genetics, was held in Toronto, ON, Canada,
on 16-20 October 2015. Approximately 700 participants attended to discuss the
latest state-of-the-art findings in this rapidly advancing and evolving field.
The following report was written by trainee travel awardees. Each was assigned
one session as a rapporteur. This manuscript represents the highlights and topics
that were covered in the plenary sessions, symposia, and oral sessions during the
conference, and contains major notable and new findings.
PMID- 27606932
TI - Who Benefits From a Tumor Bed Boost After Whole-Breast Radiotherapy?
PMID- 27606933
TI - 3D printing of novel osteochondral scaffolds with graded microstructure.
AB - Osteochondral tissue has a complex graded structure where biological,
physiological, and mechanical properties vary significantly over the full
thickness spanning from the subchondral bone region beneath the joint surface to
the hyaline cartilage region at the joint surface. This presents a significant
challenge for tissue-engineered structures addressing osteochondral defects.
Fused deposition modeling (FDM) 3D bioprinters present a unique solution to this
problem. The objective of this study is to use FDM-based 3D bioprinting and
nanocrystalline hydroxyapatite for improved bone marrow human mesenchymal stem
cell (hMSC) adhesion, growth, and osteochondral differentiation. FDM printing
parameters can be tuned through computer aided design and computer numerical
control software to manipulate scaffold geometries in ways that are beneficial to
mechanical performance without hindering cellular behavior. Additionally, the
ability to fine-tune 3D printed scaffolds increases further through our
investment casting procedure which facilitates the inclusion of nanoparticles
with biochemical factors to further elicit desired hMSC differentiation. For this
study, FDM was used to print investment-casting molds innovatively designed with
varied pore distribution over the full thickness of the scaffold. The mechanical
and biological impacts of the varied pore distributions were compared and
evaluated to determine the benefits of this physical manipulation. The results
indicate that both mechanical properties and cell performance improve in the
graded pore structures when compared to homogeneously distributed porous and non
porous structures. Differentiation results indicated successful osteogenic and
chondrogenic manipulation in engineered scaffolds.
PMID- 27606934
TI - Surface- vs Diffusion-Limited Mechanisms of Anion Exchange in CsPbBr3 Nanocrystal
Cubes Revealed through Kinetic Studies.
AB - Ion-exchange transformations allow access to nanocrystalline materials with
compositions that are inaccessible via direct synthetic routes. However,
additional mechanistic insight into the processes that govern these reactions is
needed. We present evidence for the presence of two distinct mechanisms of
exchange during anion exchange in CsPbX3 nanocrystals (NCs), ranging in size from
6.5 to 11.5 nm, for transformations from CsPbBr3 to CsPbCl3 or CsPbI3. These NCs
exhibit bright luminescence throughout the exchange, allowing their optical
properties to be observed in real time, in situ. The iodine exchange presents
surface-reaction-limited exchanges allowing all anionic sites within the NC to
appear chemically identical, whereas the chlorine exchange presents diffusion
limited exchanges proceeding through a more complicated exchange mechanism. Our
results represent the first steps toward developing a microkinetic description of
the anion exchange, with implications not only for understanding the lead halide
perovskites but also for nanoscale ion exchange in general.
PMID- 27606935
TI - Puerarin Suppresses Na+-K+-ATPase-Mediated Systemic Inflammation and CD36
Expression, and Alleviates Cardiac Lipotoxicity In Vitro and In Vivo.
AB - Puerarin, a type of isoflavone, was shown to have multiple protective effects on
myocardial injury. The objective of this study was to investigate the role of
puerarin in the progression of lipotoxic cardiomyopathy. Primary cardiomyocytes
were isolated from FATP1 transgenic (Tg) mice with lipotoxic cardiomyopathy, and
various concentrations of puerarin were used to incubate with the cardiomyocytes.
Our results showed low-dose puerarin (<=20 MUM) treatment increased the cell
viability and decreased the accumulation of free fatty acid (FFA). The data on
enzyme-linked immunosorbent assay indicated that 15 MUM puerarin treatment
greatly increased Na-K-ATPase activity and decreased C-reactive protein
secretion, thus suppressing the expression of CD36, a key contributor to the FFA
accumulation. Additionally, low-dose puerarin (<=100 mg/kg body weight)
administration improved Na-K-ATPase activity. Our data on serum analysis and
histological detection in vivo indicated that systemic inflammation, CD36-induced
lipid infiltration, and cardiomyocyte apoptosis were markedly alleviated in Tg
mice injected with 90 mg/kg dose of puerarin. Finally, the uptake rates of H
palmitate and C-glucose were monitored on ex vivo working hearts that were
obtained from wild-type (WT), Tg-control, and Tg-puerarin mice. Compared with WT
hearts, Tg hearts displayed a significant decrease in Na/K-ATPase activity and
glucose consumption rate and an increase in palmitate uptake rate and FFA
accumulation. In Tg-puerarin hearts, Na/K-ATPase activity and glucose consumption
rate were significantly rescued, and palmitate uptake and FFA accumulation were
sharply suppressed. In conclusion, low-dose puerarin suppressed Na-K-ATPase
mediated CD36 expression and systemic inflammation and alleviated cardiac
lipotoxicity in vitro and in vivo.
PMID- 27606936
TI - Notes from the Field: Varicella Outbreak Associated with Riding on a School Bus -
Muskegon County, Michigan, 2015.
AB - On December 3, 2015, Public Health-Muskegon County (PHMC) in Michigan was
notified by a local kindergarten-grade 2 school that a student aged 8 years (the
index patient) had been sent home because of a rash suspected to be varicella
(chickenpox); the rash had not been observed the previous day. Investigation by
PHMC revealed that the student was one of five siblings in household A, none of
whom had a history of having received any immunizations. During the preceding
month the index patient's two older siblings (aged 12 years and 25 years) and two
younger siblings (twins, aged 4 years) had been excluded from other schools in
this rural district because of rashes that also were suspected to be varicella.
Investigators also learned that a parent in household A had received a physician
diagnosis of herpes zoster (shingles) nearly 7 weeks earlier, on October 20,
after having been evaluated for a painful, unilateral trunk rash that had begun 3
days earlier, and for which acyclovir was prescribed. PHMC could not confirm
whether any advice regarding prevention of possible transmission of varicella
zoster virus to susceptible contacts was provided. The other children in
household A had rash onsets on November 3, November 18 (two children), and
November 22. The index patient rode a school bus and was the first student on and
the last off each day; none of the index patient's four siblings attended the
same school or rode on the same school bus as the index patient. Public health
investigators subsequently linked three more cases in children to sharing the
same school bus as the index patient.
PMID- 27606937
TI - The complex contribution of sociodemographics to decision-making power in gay
male couples.
AB - Relationship power is an important dyadic construct in close relationships that
is associated with relationship health and partner's individual health.
Understanding what predicts power in heterosexual couples has proven difficult,
and even less is known about gay couples. Resource models of power posit that
demographic characteristics associated with social status (e.g., age, income)
confer power within the relationship, which in turn shapes relationship outcomes.
We tested this model in a sample of gay male couples (N = 566 couples) and
extended it by examining race and HIV status. Multilevel modeling was used to
test associations between demographic bases of power and decision-making power.
We also examined relative associations among demographic bases and decision
making power with relationship satisfaction given the literature on power
imbalances and overall relationship functioning. Results showed that individual
income was positively associated with decision-making power, as was participant's
HIV status, with HIV-positive men reporting greater power. Age differences within
the relationship interacted with relationship length to predict decision-making
power, but not satisfaction. HIV-concordant positive couples were less satisfied
than concordant negative couples. Higher power partners were less satisfied than
lower power partners. Demographic factors contributing to decision-making power
among same-sex male couples appear to share some similarities with heterosexual
couples (e.g., income is associated with power) and have unique features (e.g.,
HIV status influences power). However, these same demographics did not reliably
predict relationship satisfaction in the manner that existing power theories
suggest. Findings indicate important considerations for theories of power among
same-sex male couples. (PsycINFO Database Record
PMID- 27606939
TI - Investigational drugs targeting cyclin-dependent kinases for the treatment of
cancer: an update on recent findings (2013-2016).
AB - INTRODUCTION: Cell cycle and gene transcription are under the control of cyclin
dependent kinases (CDKs), whose activity depends on the binding with cyclins.
Deregulated CDK activities have been reported in a majority of human cancers,
representing potential therapeutic targets. AREAS COVERED: This review provides
preclinical and clinical (phase I/II) updates of promising therapeutic compounds
targeting CDKs published between 2013 and 2016 EXPERT OPINION: First generation
pan-CDK inhibitors showed marked toxicity in clinical trials and most compounds
were discontinued. Despite their failure was ascribed also to inadequate patient
selection rules, novel pan-CDK inhibitors have entered clinical trials with still
poorly defined selection strategies. The most interesting results have been
obtained with dual CDK4/6 inhibitors and through a more accurate evaluation of
predictive biomarkers, suggesting the usefulness of CDK inhibitors for
personalized treatment. The increased knowledge on the roles of CDKs in cell
cycle and gene transcription suggests to review also the anticancer potential of
first generation CDK inhibitors by defining more appropriate rules for patients
engagement. Recent findings has highlighted CDK8 as a novel target for cancer
treatment. Indeed some biomarkers for CDK8 inhibition sensitivity have already
been proposed. CDK8 inhibition is also supposed to prevent cancer metastasis.
PMID- 27606938
TI - The Rural PILL Program: A Postdischarge Telepharmacy Intervention for Rural
Veterans.
AB - PURPOSE: To evaluate the efficacy of the Rural Pharmacological Intervention in
Late Life (PILL) program, a quality improvement initiative in which a Boston
based pharmacist provided postdischarge telepharmacy care to veterans from rural
Maine. METHODS: Using an automated screening tool, we identified 100 veterans
aged 65 and older who had an acute care admission to VA medical centers in Boston
or Maine and were at risk of problems with medication management. The PILL
pharmacist called patients the week after hospital discharge to reconcile
medications, assess adherence, and identify potentially inappropriate drugs. The
pharmacist worked with each veteran's family and providers to resolve problems
and increase support. To determine whether the intervention decreased acute care
admissions, rehospitalizations, or deaths, we matched 1 unique control to each
PILL patient by age, hospital location, length of stay, admitting service, and
reason for admission. Logistic regression was performed to determine the OR and
95% CI of the outcomes. RESULTS: Patients were discharged on an average of 16
medications and with 4.4 medication changes. Overall, 61% of patients had
clerical errors in the discharge summary, and potential clinical concerns were
identified in over 75%. Veterans who received the intervention were 70% less
likely than controls to have an acute care visit at 30 days postdischarge (7 vs
20 patients; OR = 0.30; 95% CI: 0.12-0.75). There was no difference in rates of
hospital readmission or mortality. CONCLUSION: This pharmacist-led phone-based
program was effective in decreasing acute care utilization within 30 days after
hospital discharge.
PMID- 27606940
TI - Acetyl-L-carnitine undervalued in the treatment of chemotherapy-induced
peripheral neuropathy?
PMID- 27606942
TI - Facets of Object Representation: Process and Outcome Over the Course of
Psychodynamic Psychotherapy.
AB - This study explores the effectiveness of psychodynamic psychotherapy in improving
facets of object relations (OR) functioning over the course of treatment. The
sample consisted of 75 outpatients engaged in short-term dynamic psychotherapy at
a university-based psychological services clinic. Facets of OR functioning were
assessed at pre- and posttreatment by independent raters using the Social
Cognition and Object Relations Scale-Global rating method (SCORS-G; Stein,
Hilsenroth, Slavin-Mulford, & Pinsker, 2011 ; Westen, 1995 ) from in-session
patient relational narratives. The Comparative Psychotherapy Process Scale (CPPS;
Hilsenroth, Blagys, Ackerman, Bonge, & Blais, 2005 ) was used to assess therapist
activity and psychotherapy techniques early in treatment. Independent clinical
ratings of OR functioning and psychotherapy technique were conducted and all were
found to be in the good to excellent range of reliability. Specific facets of OR
functioning improved with medium to large effect changes posttreatment. These
adaptive changes were significantly related to the incidence of psychodynamic
interpersonal (PI) techniques. Also, this study identified the role specific
psychodynamic techniques had in facilitating change in a number of underlying
dimensions of OR. Patient self-reported reliable change in symptomatology and
reliable change in facets of OR were significantly related as well. This study
highlights the utility of incorporating psychological assessment into
psychotherapy practice to assess change at the explicit (symptoms) and implicit
(OR) level. Limitations of this study, future research directions, and
implications for clinical practice are discussed.
PMID- 27606943
TI - Reproductive biology and feeding habits of the prickly dogfish Oxynotus
bruniensis.
AB - The reproductive biology and diet of prickly dogfish Oxynotus bruniensis, a deep
sea elasmobranch, endemic to the outer continental and insular shelves of
southern Australia and New Zealand, and caught as by-catch in demersal fisheries,
are described from specimens caught in New Zealand waters. A total of 53
specimens were obtained from research surveys and commercial fisheries, including
juveniles and adults ranging in size from 33.5 to 75.6 cm total length (LT ).
Estimated size-at-maturity was 54.7 cm LT in males and 64.0 cm LT in females.
Three gravid females (65.0, 67.5 and 71.2 cm LT ) were observed, all with eight
embryos. Size-at-birth was estimated to be 25-27 cm LT . Vitellogenesis was not
concurrent with embryo development. Analysis of diet from stomach contents,
including DNA identification of prey using the mitochondrial genes cox1 and
nadh2, revealed that O. bruniensis preys exclusively on the egg capsules of
holocephalans, potentially making it the only known elasmobranch with a diet
reliant solely upon other chondrichthyans. Based on spatial overlap with deep-sea
fisheries, a highly specialized diet, and reproductive characteristics
representative of a low productivity fish, the commercial fisheries by-catch of
O. bruniensis may put this species at relatively high risk of overfishing.
PMID- 27606941
TI - A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium
Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem
Cells.
AB - Human pluripotent stem cells (hPSCs) present an unprecedented opportunity to
advance human health by offering an alternative and renewable cell resource for
cellular therapeutics and regenerative medicine. The present demand for high
quality hPSCs for use in both research and clinical studies underscores the need
to develop technologies that will simplify the cultivation process and control
variability. Here we describe the development of a robust, defined and xeno-free
hPSC medium that supports reliable propagation of hPSCs and generation of human
induced pluripotent stem cells (hiPSCs) from multiple somatic cell types; long
term serial subculturing of hPSCs with every-other-day (EOD) medium replacement;
and banking fully characterized hPSCs. The hPSCs cultured in this medium for over
40 passages are genetically stable, retain high expression levels of the
pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily
differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays
an integral role in establishing a cGMP-compliant process for the manufacturing
of hiPSCs that can be used for generation of clinically relevant cell types for
cell replacement therapy applications.
PMID- 27606944
TI - Preliminary Oligomerization in a Glycolic Acid-Glycine Mixture: A Free Energy
Map.
AB - Glycolic acid and glycine can potentially self-oligomerize or co-oligomerize in
solution by forming ester and amide bonds. Using density functional theory with
implicit solvent, we have mapped a baseline free energy landscape to compare the
relative stabilities of monomers, dimers, and trimers in solution. We find that
amide bond formation is favored over ester bond formation both kinetically and
thermodynamically, although the differences decrease when zwitterionic species
are taken into account. The replacement of ester linkages by amide bonds is
favored over lengthening the oligomer, suggesting that one route to oligopeptide
formation is utilizing oligoesters as a starting point. We also find that
diketopiperazine, the cyclic dimer of glycine, is favored over the linear dimer;
however, the linear trimers are favored over their cyclic counterparts. Because
glycolic acid and glycine are dominant products from a Strecker synthesis
starting from formaldehyde and HCN, this study sheds light on potential pathways
to prebiotic formation of oligopeptides via oligoesters.
PMID- 27606945
TI - Extracorporeal Hand-Sewn Anastomosis Through a Minilaparotomy in Laparoscopic
Distal Gastrectomy.
AB - BACKGROUND: Various methods of reconstruction after laparoscopic distal
gastrectomy (LDG) have been developed and reported. In open gastrectomy,
gastroduodenostomy or gastroenterostomy is often performed with the hand-sewn
technique. Therefore, hand-sewn anastomosis was performed through a small
incision in LDG. The aim of this study was to evaluate the feasibility and safety
of LDG with hand-sewn anastomosis. METHODS: Between June 2009 and December 2015,
we assessed 263 consecutive patients who underwent LDG in our institution. In all
patients, the reconstruction procedures were performed extracorporeally with the
hand-sewn technique. The clinical characteristics, surgical outcomes, and
operation cost related to anastomosis were evaluated and compared with the other
methods. RESULTS: The average operation time was 157.5 minutes, and average blood
loss was 38.8 mL. The types of reconstruction were Billroth I, 95 cases (36.1%);
Billroth II, 165 cases (62.7%); and Roux-en-Y, 3 cases (1.1%). The overall
incidence of postoperative complications (Clavien-Dindo classification?Grade II)
was 8.0%. Anastomotic leakage was observed in 1 patient (0.4%) and anastomotic
bleeding and anastomotic stenosis in 2 patients each (0.8%). There was no
postoperative mortality. The cost of the absorbable threads used in anastomosis
is less than the cost of a linear or circular stapler, which is often used in
intracorporeal anastomosis. CONCLUSION: This procedure is similar to conventional
open surgery, and it is feasible, safe, and cost-effective. In addition, in an
institution that plans to introduce LDG, the use of our method during the
introductory phase of LDG has many advantages.
PMID- 27606946
TI - Detailed Analysis of the Binding Mode of Vanilloids to Transient Receptor
Potential Vanilloid Type I (TRPV1) by a Mutational and Computational Study.
AB - Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation
channel and a multimodal sensor protein. Since the precise structure of TRPV1 was
obtained by electron cryo-microscopy, the binding mode of representative agonists
such as capsaicin and resiniferatoxin (RTX) has been extensively characterized;
however, detailed information on the binding mode of other vanilloids remains
lacking. In this study, mutational analysis of human TRPV1 was performed, and
four agonists (capsaicin, RTX, [6]-shogaol and [6]-gingerol) were used to
identify amino acid residues involved in ligand binding and/or modulation of
proton sensitivity. The detailed binding mode of each ligand was then simulated
by computational analysis. As a result, three amino acids (L518, F591 and L670)
were newly identified as being involved in ligand binding and/or modulation of
proton sensitivity. In addition, in silico docking simulation and a subsequent
mutational study suggested that [6]-gingerol might bind to and activate TRPV1 in
a unique manner. These results provide novel insights into the binding mode of
various vanilloids to the channel and will be helpful in developing a TRPV1
modulator.
PMID- 27606947
TI - Clinical, histological, and molecular risk factors for cancer recurrence in
patients with stage II colon cancer.
AB - INTRODUCTION: The assessment of risk factors of cancer recurrence in patients
with stage II colon cancer (CC) is crucial. Our aim was to study the clinical,
histological, and molecular features associated with 3-year disease-free survival
in a series of consecutive patients with stage II CC treated in three regional
digestive oncology centers. METHODS: Clinical and histological data of all
patients after curative surgery for stage II CC, treated from 2001 until 2009,
were collected retrospectively. Histological samples were obtained and tested
prospectively for microsatellite instability using fluorescent PCR amplification.
Cox proportional hazards regression models were used to calculate P values,
hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS: Among 195
patients studied, 22 (11%) had disease recurrence during the 3-year period
following diagnosis. On multivariate analysis, only low number of lymph nodes
(HR=3.81, 95% CI: 1.19-12.19, P=0.02) and T4 status (HR=5.49, 95% CI: 1.06-28.43,
P=0.04) were associated significantly with an increased risk of relapse.
CONCLUSION: In this series of stage II CC patients, only T4 status and low number
of lymph nodes were independent risk factors for poor 3-year disease-free
survival, suggesting that patients with these features should be considered for
adjuvant chemotherapy.
PMID- 27606948
TI - Is there a relationship between gluten sensitivity and postural tachycardia
syndrome?
AB - BACKGROUND: We have noticed that patients with postural tachycardia syndrome
(PoTS) were placing themselves on a gluten-free diet without medical
consultation. Therefore, we aimed to evaluate the prevalence of coeliac disease
and self-reported gluten sensitivity in a cohort of patients with PoTS and
compare this with local population data. METHODS: A total of 100 patients with
PoTS were recruited to complete a questionnaire that screened for gluten
sensitivity, related symptoms and dietary habits. Patients were also assessed for
coeliac disease. For comparison, the local coeliac prevalence was determined from
a total of 1200 controls (group 1) and a further 400 controls (group 2),
frequency matched for age and sex, who completed the same questionnaire. RESULTS:
Overall, 4/100 (4%) patients with PoTS had serology and biopsy-proven coeliac
disease. This was significantly higher than the local population prevalence of
coeliac disease (12/1200, 1%; odds ratio: 4.1, 95% confidence interval: 1.3-13.0;
P=0.03). PoTS patients also had a higher prevalence of self-reported gluten
sensitivity (42 vs. 19%, respectively; odds ratio: 3.1, 95% confidence interval:
2.0-5.0; P<0.0001) compared with age-matched and sex-matched controls.
CONCLUSION: This is the first study to suggest a potential association between
gluten-related disorders and PoTS. A prospective study evaluating this
relationship further may enable a better understanding and management of these
conditions.
PMID- 27606950
TI - JAK2 in the Diagnosis and Treatment of Lymphoid Malignancies: A Review of the
Literature.
AB - In 2016, there will be an estimated 6,590 new cases of acute lymphocytic leukemia
and 18,960 new cases of chronic lymphocytic leukemia in the United States. These
and other lymphoid malignancies have a key player in common, JAK2, an enzyme from
the Janus kinase (JAK) family. Deviations from the normal functioning of JAK2,
particularly in the JAK-signal transducer and activator of transcription (STAT)
pathway, can disrupt homeostasis and drive the accumulation of intermediate
progenitors, contributing to the development of myeloid and lymphoid
malignancies. In this review, the recent literature on JAK2 mutations in lymphoid
malignancies is summarized, concluding with a discussion of the treatment of
lymphoid malignancies. New directions for future research have been underlined to
advance the clinical management of lymphoid malignancies.
PMID- 27606949
TI - Influence of periampullary diverticulum on the occurrence of pancreaticobiliary
diseases and outcomes of endoscopic retrograde cholangiopancreatography.
AB - BACKGROUND AND AIM: Periampullary diverticulum (PAD) is frequently encountered in
patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). The
aim of this study was to investigate the association of PAD with
pancreaticobiliary diseases as well as the impact of PAD on the technical success
of ERCP and different methods of bile duct stone extraction. PATIENTS AND
METHODS: A total of 1489 cases of patients with PAD were identified from 6390
patients who underwent ERCP. These patients were compared with 1500 controls
without PAD in terms of biliary stone formation, technical success, and
complications of ERCP. RESULTS: Patients with PAD had increased prevalence of
bile duct stones, gallstones, and cholangitis (P<0.01). Successful cannulation
rates were similar in the PAD and the control group (98.59 vs. 99.07%, P=0.225).
The incidence of complications did not differ between the PAD and the control
group. Successful stone removal rate of endoscopic sphincterotomy (EST) was lower
in the PAD group than in the control group (83.53 vs. 94.31%, P=0.005). In
patients with PAD, the rate of successful stone removal was lower in the EST
group than in the endoscopic papillary balloon dilation (EPBD) and EPBD combined
with limited EST (ESBD) group. The rates of complications were similar among
different treatments (EST, EPBD, or ESBD) in patients with PAD. CONCLUSION: PAD
is associated with bile duct stones, gallstones, and cholangitis. In addition,
PAD should not be considered a barrier to a successful cannulation. Moreover, EST
is less effective than EPBD and ESBD in patients with PAD, whereas EST, EPBD, and
ESBD are equally safe in patients with PAD.
PMID- 27606951
TI - Solution and solid state conformational preferences of a family of cyclic
disulphide bridged tetrapeptides.
AB - A set of cyclic tetrapeptides of the general form cyclo (Boc-Cys-Pro-X-Cys-OMe)
with X being L-/D-Ala, L-/D-Val, and L-/D-Trp was synthesized. These peptides
serve as model systems for structure elucidation in solution and feature a
variety of structural motifs - namely a beta-turn with intramolecular hydrogen
bonding interactions, cis/trans isomerism, and a disulphide bond. In this work,
we performed a comprehensive structural analysis focussing on their beta-turn
conformational preferences using NMR, VCD, and Raman spectroscopy. Our results
provide evidence for a strong influence of a single stereocenter on the
structures of the peptides whereas solvent polarity does not significantly affect
them. Additionally, the solid state conformational preferences were studied by
crystal structure analysis. Overall, a general trend for the conformational
preferences of this set of peptides can be concluded from the results of the
complementary investigations.
PMID- 27606952
TI - Normative Values of the Sport Concussion Assessment Tool 3 (SCAT3) in High School
Athletes.
AB - OBJECTIVE: Establish sex, age, and concussion history-specific normative baseline
sport concussion assessment tool 3 (SCAT3) values in adolescent athletes. DESIGN:
Prospective cohort. SETTING: Seven Wisconsin high schools. PARTICIPANTS: Seven
hundred fifty-eight high school athletes participating in 19 sports. INDEPENDENT
VARIABLES: Sex, age, and concussion history. MAIN OUTCOME MEASURES: Sport
Concussion Assessment Tool 3 (SCAT3): total number of symptoms; symptom severity;
total Standardized Assessment of Concussion (SAC); and each SAC component
(orientation, immediate memory, concentration, delayed recall); Balance Error
Scoring System (BESS) total errors (BESS, floor and foam pad). RESULTS: Males
reported a higher total number of symptoms [median (interquartile range): 0 (0-2)
vs 0 (0-1), P = 0.001] and severity of symptoms [0 (0-3) vs 0 (0-2), P = 0.001]
and a lower mean (SD) total SAC [26.0 (2.3) vs 26.4 (2.0), P = 0.026], and
orientation [5 (4-5) vs 5 (5-5), P = 0.021]. There was no difference in baseline
scores between sex for immediate memory, concentration, delayed recall or BESS
total errors. No differences were found for any test domain based on age.
Previously, concussed athletes reported a higher total number of symptoms [1 (0
4) vs 0 (0-2), P = 0.001] and symptom severity [2 (0-5) vs 0 (0-2), P = 0.001].
BESS total scores did not differ by concussion history. CONCLUSION: This study
represents the first published normative baseline SCAT3 values in high school
athletes. Results varied by sex and history of previous concussion but not by
age. The normative baseline values generated from this study will help clinicians
better evaluate and interpret SCAT3 results of concussed adolescent athletes.
PMID- 27606953
TI - Incidence of Iron Deficiency and Iron Deficient Anemia in Elite Runners and
Triathletes.
AB - OBJECTIVE: To assess the incidence of iron deficiency (ID), and iron deficient
anemia (IDA) within a cohort of highly trained runners and triathletes, and to
examine the association of oral iron supplementation history with serum ferritin
(sFe) and hemoglobin (Hb) concentrations. METHODS: A retrospective analysis of
routine blood test data taken from 2009 to 2015 from (n = 38) elite level runners
and triathletes between the ages of 21 to 36 years. Oral iron supplement intake
was assessed through a questionnaire. RESULTS: Triathletes (female, FT; male, MT)
and runners (female, FR; male, MR) had higher incidence of at least 1 episode of
ID (FT 60.0%, MT 37.5%, FR 55.6%, MR 31.3%) compared with values reported in the
literature for endurance athletes (20%-50% females, 0%-17% males). Male
triathletes and runners had a higher incidence of IDA than their female teammates
(25% MT, 20% FT, 6.3% for MR, 0% FR), a finding which has previously not been
reported. Hemoglobin concentrations were low, with incidence of Hb <140 g/L in
men occurring at least once in 87.5% of triathletes, and 31.3% of runners, and Hb
<120 g/L in women occurring at least once in 20% of triathletes, but 0% of
runners. Although the athletes were appropriately treated with oral iron (mean 94
+/- 115 mg/d), there was no observed correlation between iron intake and sFe or
Hb. CONCLUSIONS: Even with monitoring and treatment in place, ID and IDA are
significant concerns for the health and performance of elite runners and
triathletes, and this issue affects males and females.
PMID- 27606954
TI - Statistically Analyzed Photoresponse of Elastically Bent CdS Nanowires Probed by
Light-Compatible In Situ High-Resolution TEM.
AB - We demonstrate that high resolution transmission electron microscopy (HRTEM)
paired with light illumination of a sample and its electrical probing can be
utilized for the in situ study of initiated photocurrents in free-standing
nanowires. Morphology, phase and crystallographic information from numerous
individual CdS nanowires is obtained simultaneously with photocurrent
measurements. Our results indicate that elastically bent CdS nanowires possessing
a wurtzite structure show statistically unchanged values of ON/OFF
(photocurrent/dark current) ratios. Photocurrent spectroscopy reveals red shifts
of several nanometers in the cutoff wavelength after nanowire bending. This
results from deformation-induced lattice strain and associated changes in the
nanowire band structure, as confirmed by selected area electron diffraction
(SAED) analyses and density functional tight binding (DFTB) simulations. The
ON/OFF ratio stabilities and photocurrent spectroscopy shift of bent CdS
nanowires are important clues for future flexible electronics, optoelectronics,
and photovoltaics.
PMID- 27606955
TI - Potentially Serious Drug-Drug Interactions in Older Patients Hospitalized for
Acute Ischemic and Hemorrhagic Stroke.
AB - BACKGROUND: Polypharmacy is very common in older persons and it is associated
with inappropriate prescribing and potential drug-drug interactions (DDIs). Aims
of this study were to identify prevalence of DDIs in older persons with acute
stroke and to evaluate the association between stroke and DDIs. METHODS: One
hundred forty-six patients admitted with diagnosis of acute stroke were enrolled.
The therapeutic regimen of patients was analyzed at admission to identify the
number of DDIs, prevalence and sorts of serious DDIs according to subtype of
acute stroke (ischemic or hemorrhagic) and to its recurrence. RESULTS: Five
hundred eighty-two DDIs were identified: 18 mild, 415 moderate and 149 serious.
Sixty-one percent of patients were exposed to at least one serious DDI. A higher
percentage of patients were exposed to at least one serious DDI among those with
a recurring ischemic event compared to those with a first event (74 vs. 50%; p <
0.01, respectively). Serious DDIs potentially associated with an increased risk
of a cerebral event were identified in 19 (17%) patients with ischemic stroke,
and in 7 (19%) patients with hemorrhagic stroke. CONCLUSIONS: The prevalence of
serious DDIs was high in aging patients with acute stroke but different according
to subtype and recurrence of the cerebrovascular event.
PMID- 27606956
TI - Recent progress in understanding skills and impairments in social cognition.
AB - PURPOSE OF REVIEW: Social interaction is affected in many different developmental
disorders; indeed, the new Diagnostic and Statistical Manual of Mental Disorders
has introduced social cognition as one of six core components of neurocognitive
functioning. Social cognition is not one thing, but a wide range of putative
processes, which may be differentially affected in different clinical groups.
This review focuses on recent advances in one aspect of social cognition, 'theory
of mind' (ToM, representing what people think), and one core clinical group,
autism spectrum disorder (ASD). RECENT FINDINGS: It is 30 years since impaired
ToM was proposed as an explanation for ASD social difficulties, and recently
there has been a widening of interest to other clinical groups. ToM has been
found to be distinct from emotion recognition and empathy. Recent research on ASD
has focused increasingly on atypical sensory responses and commonly comorbid
conditions. Interventions for social deficits, including ToM training and
oxytocin, have shown mixed results to date. SUMMARY: Heterogeneity poses a major
obstacle to current research. Theoretical and empirical refinements are needed to
elucidate neurocognitive and aetiological underpinnings of sociocognitive
processes and inform clinical advances.
PMID- 27606958
TI - Ethical issues in pediatric genetic testing and screening.
AB - PURPOSE OF REVIEW: Developments in genetic test technologies enable a detailed
analysis of the genomes of individuals across the range of human development from
embryos to adults with increased precision and lower cost. These powerful
technologies raise a number of ethical issues in pediatrics, primarily because of
the frequent lack of clinical utility of genetic information, the generation of
secondary results and questions over the proper scope of parental authority for
testing. RECENT FINDINGS: Several professional organizations in the fields of
genetics and pediatrics have published new guidance on the ethical, legal, and
policy issues relevant to genetic testing in children. The roles of predictive
testing for adult-onset conditions, the management of secondary findings and the
role of informed consent for newborn screening remain controversial. However,
research and experience are not demonstrating serious adverse psychosocial
impacts from genetic testing and screening in children. The use of these
technologies is expanding with the notion that the personal utility of test
results, rather than clinical utility, may be sufficient to justify testing.
SUMMARY: The use of microarray and genome sequencing technologies is expanding in
the care of children. More deference to parental decision-making is evolving in
contexts wherein information and counseling can be made readily available.
PMID- 27606957
TI - The microbiome in asthma.
AB - PURPOSE OF REVIEW: Asthma is a complex and heterogeneous disease with strong
genetic and environmental components that manifests within a variety of clinical
features and diverse patterns of immune responses. Asthma prevalence has
dramatically increased over the last decade in Westernized societies, thereby
suggesting a key function of environmental factors in disease promotion and
development. RECENT FINDINGS: 'Early-life' microbial exposure and bacterial
colonization are crucial for the maturation and the education of the immune
system. The commensal flora is also critical in order to maintain immune
homeostasis at the mucosal surfaces and may consequently play an important
function in allergic disease development. Recent evidence demonstrates that
asthma influences and is also impacted by the composition and function of the
human intestinal and respiratory microbiome. SUMMARY: In this review, we
summarize the most recent findings on how asthma development is connected with
respiratory and intestinal microbial dysbiosis. We highlight and discuss recent
research that reveals the existence of a 'gut-lung' microbial axis and its impact
on asthma development. We also analyze how 'early-life' microbial exposure
affects the immune response and the consequences for asthma development.
PMID- 27606959
TI - Rice Dwarf Virus P2 Protein Hijacks Auxin Signaling by Directly Targeting the
Rice OsIAA10 Protein, Enhancing Viral Infection and Disease Development.
AB - The phytohormone auxin plays critical roles in regulating myriads of plant growth
and developmental processes. Microbe infection can disturb auxin signaling
resulting in defects in these processes, but the underlying mechanisms are poorly
understood. Auxin signaling begins with perception of auxin by a transient co
receptor complex consisting of an F-box transport inhibitor response 1/auxin
signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA)
protein. Auxin binding to the co-receptor triggers ubiquitination and 26S
proteasome degradation of the Aux/IAA proteins, leading to subsequent events,
including expression of auxin-responsive genes. Here we report that Rice dwarf
virus (RDV), a devastating pathogen of rice, causes disease symptoms including
dwarfing, increased tiller number and short crown roots in infected rice as a
result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds
OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S
proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing
wild-type or a dominant-negative (degradation-resistant) mutant of OsIAA10
phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown
of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal
a previously unknown mechanism of viral protein reprogramming of a key step in
auxin signaling initiation that enhances viral infection and pathogenesis.
PMID- 27606960
TI - Detection of Chikungunya Virus Circulation Using Sugar-Baited Traps during a
Major Outbreak in French Guiana.
PMID- 27606961
TI - In vivo kinematics of the thumb during flexion and adduction motion: Evidence for
a screw-home mechanism.
AB - The thumb plays a crucial role in basic hand function. However, the kinematics of
its entire articular chain have not yet been quantified. Such investigation is
essential to improve our understanding of thumb function and to develop better
strategies to treat thumb joint pathologies. The primary objective of this study
is to quantify the in vivo kinematics of the trapeziometacarpal (TMC) and
scaphotrapezial (ST) joints during flexion and adduction of the thumb. In
addition, we want to evaluate the potential coupling between the TMC and ST
joints during these tasks. The hand of 16 asymptomatic women without signs of
thumb osteoarthritis were CT scanned in positions of maximal thumb extension,
flexion, abduction, and adduction. The CT images were segmented and three
dimensional surface models of the radius, scaphoid, trapezium, and the first
metacarpal were created for each thumb motion. The corresponding rotations
angles, translations, and helical axes were calculated for each sequence. The
analysis shows that flexion and adduction of the thumb result in a three
dimensional rotation and translation of the entire articular chain, including the
trapezium and scaphoid. A wider range of motion is observed for the first
metacarpal, which displays a clear axial rotation. The coupling of axial rotation
of the first metacarpal with flexion and abduction during thumb flexion supports
the existence of a screw-home mechanism in the TMC joint. In addition, our
results point to a potential motion coupling between the TMC and ST joints and
underline the complexity of thumb kinematics. (c) 2016 Orthopaedic Research
Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1556-1564, 2017.
PMID- 27606962
TI - Lactobacillus is able to alter the virulence and the sensitivity profile of
Candida albicans.
AB - AIMS: The study investigated whether the interaction with Lactobacillus rhamnosus
(ATCC7469) interfere with the expression of virulence factors by Candida albicans
(ATCC18804). METHODS AND RESULTS: These micro-organisms were grown in biofilms
for 24, 48 and 72 h, Candida was isolated and the expression of the major
virulence factors were investigated. The production of phospholipase, protease
and haemolysin were observed in appropriate media; observation of germ tubes
formation in serum; biofilm formation, after growth in microtitre plates and
reading in spectrophotometer. Candida was also tested for antifungal sensitivity
to amphotericin B, fluconazole and ketoconazole. The results were compared with
the cells of Candida grown in the absence of lactobacilli (control group).
Candida cells, which interacted with Lact. rhamnosus (test group), showed
significantly lower proteinase and haemolysin activity, when compared with
control group. The germ tube formation and biofilm formation capacity also
decreased in tested groups, which demonstrated alterations in susceptibility to
antifungal drugs. CONCLUSIONS: The results suggest that Lact. rhamnosus is able
to influence the expression of virulence factors by C. albicans and can alter its
antifungal sensitivity profile. SIGNIFICANCE AND IMPACT OF THE STUDY: These
results suggest reduction in the pathogenicity of Candida and improvement in
candidiasis therapy and control.
PMID- 27606964
TI - Targeting blood products transfusion in trauma: what is the role of
thromboelastography?
AB - Viscoelastic hemostatic assays (VHAs), mainly thromboelastography (TEG) and the
rotational thromboelastometry (ROTEM), provide global information on clot
formation and dissolution at patient bedside, allowing fast identification of
coagulation disorders. In trauma patients, VHAs are able to predict massive
transfusion and mortality. These devices might also be used for applying targeted
administration of procoagulant factors (e.g. fibrinogen concentrate) as an
alternative to or in addition to using predefined fixed ratios of red blood
cells: platelets: fresh frozen plasma/cryoprecipitate. These goal-directed,
individualized treatment algorithms seem to reduce blood product transfusion
without deleterious effects on patient outcome. Nevertheless, a clear outcome
benefit of using VHAs remains to be demonstrated in trauma patients.
PMID- 27606963
TI - Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term
Newborn Infants and Adults in Contrast to IL-8.
AB - We have previously observed that neutrophils from neonates exhibit different
migratory responses to intermediate and end-target chemoattractants compared to
adults. The aim of this study was to investigate the effect of the
chemoattractants IL-8 (intermediate) and formyl-methionyl-leucyl-phenylalanine
(fMLP; end-target) on cell surface receptor expression involved in adhesion,
migration and granule release of neutrophils from term newborn infants and
adults. Heparinized cord blood from 16 healthy term newborn infants delivered by
caesarean section and peripheral blood from 17 healthy adults were incubated with
1 MUm IL-8 or 0.1 MUm fMLP, previously defined as optimal inducers of neutrophil
migration. The leukocytes were labelled with antibodies to cell surface receptors
(CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182).
Receptor expression was quantified by flow cytometry analysis. Upregulation of
CD11b and downregulation of CD88 and CD182 after stimulation with IL-8 were more
pronounced in adults than in neonates (P < 0.05, P < 0.05 and P <= 0.001,
respectively), whereas fMLP induced changes in receptor expression that were of
the same magnitude in neutrophils from neonates as from adults. We observed
similar expression of receptors that mediate adhesion, migration, granule
activation and phagocytosis induced by fMLP in neutrophils from neonates and
adults. In contrast, differences between neonates and adults, induced by IL-8,
suggest that the neutrophil response to intermediate chemoattractants might lead
to a compromised infectious response in newborn infants.
PMID- 27606965
TI - Correlation between Viscoelastic Moduli and Atomic Rearrangements in Metallic
Glasses.
AB - Dynamical moduli, such as storage and loss moduli, characterize the
viscoelasticity of materials (i.e., time-dependent elasticity) and convey
important information about the relaxation processes of glasses and supercooled
liquids. A fundamental question is what ultimately determines them in glassy
materials. Here, for several model metallic glasses, we demonstrate that both the
storage and loss moduli are uniquely determined by the most probable atomic
nonaffine displacements, regardless of temperature or frequency. Moreover, the
fast-moving atoms (which contribute to dynamical heterogeneity) do not contribute
explicitly to the moduli. Our findings provide a physical basis for the origin of
viscoelasticity in metallic glasses.
PMID- 27606966
TI - Erratum: Lineage-Specific Early Differentiation of Human Embryonic Stem Cells
Requires a G2 Cell Cycle Pause.
PMID- 27606967
TI - Asthma Trajectories in a Population-based Birth Cohort. Impacts of Air Pollution
and Greenness.
AB - RATIONALE: The heterogeneity of asthma phenotypes may explain inconsistencies in
observed associations with environmental exposures. OBJECTIVES: To identify
trajectories of childhood asthma and to characterize the potential impact of
residential greenness and air pollution on asthma trajectory subgroups. METHODS:
Linked administrative databases of medical visits were used to define the
occurrence and recurrence of asthma over a 10-year follow-up period within a
population-based birth cohort of more than 65,000 children. Group-based
trajectory modeling was used to identify unique asthma trajectories. Weighted
multinomial regression was used to assess the relationship between asthma
trajectories and risk factors, including environmental exposures. MEASUREMENTS
AND MAIN RESULTS: Group-based trajectory modeling distinguished four
trajectories: one with no asthma representing 88.8% of the cohort, one with
transient asthma (5.6% of the cohort), and two trajectories with chronic asthma
with early (<1 yr; 1.5%) and late (<3 yr; 4.1%) onset during early childhood.
These trajectories differed with respect to socioeconomic markers and modifiable
risk factors, including maternal smoking and breastfeeding initiation. After
accounting for sex, parity, breastfeeding, term birth weight, household income,
maternal education, delivery mode, and smoking, an interquartile increase in
nitrogen dioxide exposure increased the risk of membership in the early and late
onset chronic asthma trajectories, relative to subjects without asthma, by 50%
and 20%, respectively (weighted risk ratio, 1.5 and 1.2; 95% confidence interval,
1.2-1.9 and 1.0-1.4). Greenness was not associated with any of the asthma
trajectories. CONCLUSIONS: Traffic-related air pollution increased the
probability of a chronic asthma trajectory.
PMID- 27606968
TI - Incorporating gender, equity, and human rights into the action planning process:
moving from rhetoric to action.
AB - BACKGROUND: Mainstreaming of gender, equity, and human rights (GER) is an
important focus of the World Health Organization (WHO) and other UN
organizations. This paper explores the role of action plans in mainstreaming GER.
This paper is informed by a theory-driven evaluation lens. DESIGN: A theory of
change framework explored the following seven dimensions of how action plans can
implement mainstreaming of GER: awareness of the foundations of GER;
understanding of context; planning to impact GER; implementation for GER;
monitoring, evaluation, and learning; planning for sustainability; agenda setting
and buy-in. The seven dimensions were used to analyze the action plans. Reviewers
also explored innovations within each of the action plans for the seven
dimensions. RESULTS: GER mainstreaming is more prominent in the foundation,
background, and planning components of the plan but becomes less so along the
theory of change including implementation; monitoring and evaluation;
sustainability; and agenda setting and buy-in. CONCLUSIONS: Our analysis
demonstrates that much more can be done to incorporate GER considerations into
the action planning process. Nine specific recommendations are identified for WHO
and other organizations. A theory-driven approach as described in the paper is
potentially helpful for developing clarity by which action plans can help with
mainstreaming GER considerations.
PMID- 27606969
TI - Regional-level estimation of expected years of life lost attributable to
overweight and obesity among Mexican adults.
AB - BACKGROUND: Excess body weight has become a major public health problem
worldwide, and the burden of overweight and obesity was calculated in this work
from a health economics perspective. OBJECTIVE: To estimate the burden of disease
attributable to overweight and obesity among males and females aged 20 years and
older using years of life lost (YLL) and age-standardized YLL rates (ASYLL), and
to rank the leading causes of premature death. DESIGN: A cross-sectional study
took place (2010-2014) and 6,054 deaths were analyzed. Thirteen basic causes of
death associated with overweight or obesity were included. The population
attributable fraction (PAF), YLL, and ASYLL were calculated. RESULTS: The overall
burden attributable to overweight and obesity was 36,087 YLL, and the estimated
ASYLL per 10,000 persons was 1,098 and 1,029 in males and females, respectively.
Type 2 diabetes mellitus was the main cause of premature death (males, 968 ASYLL;
females, 772 ASYLL). CONCLUSIONS: Overweight and obesity are major risk factors
of chronic diseases that are main causes of premature death in the study
population. Strategies for preventing overweight and obesity may decrease the
incidence and mortality associated with these non-communicable diseases. ASYLL
seems to be an indicator that is particularly well adapted to decision-making in
public health.
PMID- 27606970
TI - Energy-Level Modulation of Small-Molecule Electron Acceptors to Achieve over 12%
Efficiency in Polymer Solar Cells.
AB - Fine energy-level modulations of small-molecule acceptors (SMAs) are realized via
subtle chemical modifications on strong electron-withdrawing end-groups. The two
new SMAs (IT-M and IT-DM) end-capped by methyl-modified dicycanovinylindan-1-one
exhibit upshifted lowest unoccupied molecular orbital (LUMO) levels, and hence
higher open-circuit voltages can be observed in the corresponding devices.
Finally, a top power conversion efficiency of 12.05% is achieved.
PMID- 27606971
TI - Optically Evolved Assembly Formation in Laser Trapping of Polystyrene
Nanoparticles at Solution Surface.
AB - Assembling dynamics of polystyrene nanoparticles by optical trapping is studied
with utilizing transmission/reflection microscopy and reflection
microspectroscopy. A single nanoparticle assembly with periodic structure is
formed upon the focused laser irradiation at solution surface layer and
continuously grows up to a steady state within few minutes. By controlling
nanoparticle and salt concentrations in the colloidal solution, the assembling
behavior is obviously changed. In the high concentration of nanoparticles, the
assembly formation exhibits fast growth, gives large saturation size, and leads
to dense packing structure. In the presence of salt, one assembly with the
elongated aggregates was generated from the focal spot and 1064 nm trapping light
was scattered outwardly with directions, while a small circular assembly and
symmetrical expansion of the 1064 nm light were found without salt. The present
nanoparticle assembling in optical trapping is driven through multiple scattering
in gathered nanoparticles and directional scattering along the elongated
aggregates derived from optical association of nanoparticles, which dynamic
phenomenon is called optically evolved assembling. Repetitive trapping and
release processes of nanoparticles between the assembly and the surrounding
solution always proceed, and the steady state at the circular assembly formed by
laser trapping is determined under optical and chemical equilibrium.
PMID- 27606973
TI - Maintenance of remission and monotherapy status over 66 months in patients with
psoriatic arthritis receiving etanercept.
AB - OBJECTIVES: To determine if patients with psoriatic arthritis (PsA) who achieved
remission within 6 months with etanercept (ETN) treatment (with or without
methotrexate) were able to maintain remission over 66 months. Monotherapy status
over the study duration was also monitored. METHODS: This was a post hoc analysis
of PROVE (NCT00938015), a multicentre, observational study into the long-term
adherence of ETN performed in rheumatology clinics in Belgium. To be included in
PROVE, patients had active PsA and were either already receiving ETN treatment or
had recently been prescribed it. Patients who achieved remission (defined as zero
joints with synovitis) after 6 months of ETN treatment were monitored for
maintenance of remission at each subsequent visit. In addition, patients on ETN
monotherapy at Month 6 were observed. RESULTS: 303 patients participated and 156
(51.5%) patients completed 66 months of ETN treatment. The mean (standard
deviation [SD]) disease duration was 7.5 (7.4) years and the majority had
polyarticular-type PsA (87.1%). Overall, 142 patients achieved remission after 6
months of ETN treatment. Among the 83 patients who were in remission at Month 6
and remained in the study until the end, 72 (86.7%) were still in remission at
Month 66. After 6 months, 66 patients were receiving ETN monotherapy and the
majority continued with it until Month 66 (n=22/26; 84.6%). CONCLUSIONS: Within
this patient population, remission was achieved quickly and was sustained in the
long-term. Of those patients who were receiving monotherapy, most continued with
this treatment strategy for the duration of the study.
PMID- 27606974
TI - The toxicology mechanism of endophytic fungus and swainsonine in locoweed.
AB - Locoweed is a perennial herbaceous plant included in Astragalus spp. and
Oxytropis spp. that contains the toxic indolizidine alkaloid swainsonine. The
livestock that consume locoweed can suffer from a type of toxicity called
locoism. There are aliphaticnitro compounds, selenium, selenium compounds, and
alkaloids in locoweed. The toxic component in locoweed has been identified as
swainsonine, an indolizidine alkaloid. Swainsonine inhibits lysosomal a
mannosidase and mannosidase II, resulting in altered oligosaccharide degradation
and incomplete glycoprotein processing. Corresponding studies on endophytic fungi
producing swainsonine have been isolated from a variety of locoweed, and these
endophytic fungi and locoweed have a close relationship. Endophytic fungi can
promote the growth of locoweed and increase swainsonine production. As a result,
livestock that consume locoweed exhibit several symptoms, including dispirited
behavior, staggering gait, chromatopsia, trembling, ataxia, and cellular vacuolar
degeneration of most tissues by pathological observation. Locoism results in
significant annual economic losses. Therefore, in this paper, we review the
current research on locoweed, including that on locoweed species distribution in
China, endophyte fungus in locoweed, the toxicology mechanism of locoweed, and
the swainsonine effect on reproduction.
PMID- 27606975
TI - Three-Year Follow-Up of a Patient with a Giant Bulla Treated by Bronchoscopic
Intrabullous Autologous Blood Instillation.
PMID- 27606976
TI - The epidemiology of Clostridium difficile infection in patients with cancer.
AB - INTRODUCTION: Clostridium difficile infection (CDI) is a significant cause of
healthcare-associated diarrhoea, and the emergence of endemic strains resulting
in poorer outcomes is recognised worldwide. Patients with cancer are a specific
high-risk group for development of infection. Areas covered: In this review,
modifiable and non-modifiable risk factors for CDI in adult patients with
haematological malignancy or solid tumours are evaluated. In particular, the
contribution of antimicrobial exposure, hospitalisation and gastric acid
suppression to risk of CDI are discussed. Recent advances in CDI treatment are
outlined, namely faecal microbiota transplantation and fidaxomicin therapy for
severe/refractory infection in cancer populations. Outcomes of CDI, including
mortality are presented, together with the need for valid severity rating tools
customised for cancer populations. Expert commentary: Future areas for research
include the prognostic value of C. difficile colonisation in cancer patients and
the potential impact of dedicated antimicrobial stewardship programs in reducing
the burden of CDI in cancer units.
PMID- 27606972
TI - A developmental neuroscience perspective on affect-biased attention.
AB - There is growing interest regarding the impact of affect-biased attention on
psychopathology. However, most of the research to date lacks a developmental
approach. In the present review, we examine the role affect-biased attention
plays in shaping socioemotional trajectories within a developmental neuroscience
framework. We propose that affect-biased attention, particularly if stable and
entrenched, acts as a developmental tether that helps sustain early
socioemotional and behavioral profiles over time, placing some individuals on
maladaptive developmental trajectories. Although most of the evidence is found in
the anxiety literature, we suggest that these relations may operate across
multiple domains of interest, including positive affect, externalizing behaviors,
drug use, and eating behaviors. We also review the general mechanisms and neural
correlates of affect-biased attention, as well as the current evidence for the co
development of attention and affect. Based on the reviewed literature, we propose
a model that may help us better understand the nuances of affect-biased attention
across development. The model may serve as a strong foundation for ongoing
attempts to identify neurocognitive mechanisms and intervene with individuals at
risk. Finally, we discuss open issues for future research that may help bridge
existing gaps in the literature.
PMID- 27606977
TI - The emerging role of long non-coding RNAs in cutaneous melanoma.
AB - Malignant melanoma is a highly aggressive form of skin cancer, the incidence of
which is rising rapidly. Although MAPK-targeting therapies and immune checkpoint
blockade are emerging as attractive therapeutic approaches, their utility is
limited to only a subset of patients who often acquire resistance. A better
understanding of the aetiologies and genetic underpinnings of melanoma is
therefore critical for the development of adjuvant or alternative therapeutic
strategies aimed at increasing the proportion of responders and improving
treatment efficacy. A key step in identifying novel therapeutic targets may be
the shift in focus from the protein-coding components to the non-coding portion
of the genome. The latter, representing about 98% of the genome, serves as a
template for the transcription of many thousands of long non-coding RNAs
(lncRNAs). Intriguingly, lncRNA loci are frequently mutated or altered in a
variety of cancers, including melanoma, and there is growing evidence that
lncRNAs can function as cancer-causing oncogenes or tumour suppressors. In this
review, we summarize recent data highlighting the importance of lncRNAs in the
biology of melanoma and their potential utility as biomarkers and therapeutic
targets.
PMID- 27607019
TI - Detoxification of Chemical Warfare Agents Using a Zr6 -Based Metal-Organic
Framework/Polymer Mixture.
AB - Owing to their high surface area, periodic distribution of metal sites, and water
stability, zirconium-based metal-organic frameworks (Zr6 -MOFs) have shown
promising activity for the hydrolysis of nerve agents GD and VX, as well as the
simulant, dimethyl 4-nitrophenylphosphate (DMNP), in buffered solutions. A hurdle
to using MOFs for this application is the current need for a buffer solution.
Here the destruction of the simulant DMNP, as well as the chemical warfare agents
(GD and VX) through hydrolysis using a MOF catalyst mixed with a non-volatile,
water-insoluble, heterogeneous buffer is reported. The hydrolysis of the simulant
and nerve agents in the presence of the heterogeneous buffer was fast and
effective.
PMID- 27607020
TI - Versatile Picklocks To Access All Opioid Receptors: Tuning the Selectivity and
Functional Profile of the Cyclotetrapeptide c[Phe-d-Pro-Phe-Trp] (CJ-15,208).
AB - Recently, the tryptophan-containing noncationizable opioid peptides emerged with
atypical structure and unexpected in vivo activity. Herein, we describe analogs
of the naturally occurring mixed kappa/MU-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ
15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon
enlarging macrocycle size, giving the MU-agonist 9 or the delta-antagonist 10
characterized by low nanomolar affinity. In particular, the MU-agonist c[beta-Ala
d-Pro-Phe-Trp] 9 was shown to elicit potent antinociception in a mouse model of
visceral pain upon systemic administration.
PMID- 27607021
TI - Evaluating a filtering and recirculating system to reduce dust drift in simulated
sowing of dressed seed and abraded dust particle characteristics.
AB - BACKGROUND: The pneumatic precision drills used in maize sowing can release dust
owing to abrasion of dressed seed; the drift of dust containing insecticide
active ingredients is harmful to honey bees. Therefore, we developed a device for
drills that uses partial recirculation and filtration of the air by means of an
antipollen and an electrostatic filter. RESULTS: Tests were carried out by
simulating the sowing of seed treated with imidacloprid, thiamethoxam,
clothianidin and fipronil. Dust released by the drill in different configurations
was analysed to assess its mass and active ingredient concentration, size
distribution and particle number concentration. In general, particles with a
diameter smaller than 2.5 and 10 um represent about 40 and 75% of the total dust
mass respectively. The finest size fraction (<1 um) contains a higher content of
active ingredient. The prototype equipped with both antipollen and electrostatic
filters always showed a reduction in dust emission greater than 90% in terms of
both total mass and active ingredient amount, with a greater efficiency in the
reduction in particles below 4 um. CONCLUSION: This study presents an engineering
solution addressing dust losses during sowing, contributes to the description of
abrasion dust fractions and provides suggestions for further development of the
prototype. (c) 2016 Society of Chemical Industry.
PMID- 27607022
TI - Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via
Targeting PPARgamma.
AB - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a
critical role in protecting against distinct brain damages, including ischemia.
Our previous data have shown that the protein level of PPARgamma is increased in
the cortex after middle cerebral artery occlusion (MCAO); PPARgamma up-regulation
contributes to PPARgamma activation and is effective in reducing ischemic damage
to brain. However, the regulatory mechanism of PPARgamma after focal cerebral
ischemia in rats is still unclear. In this study, we evaluated the effect of
microRNA on PPARgamma in rats subjected to MCAO. METHODS: Focal cerebral ischemia
was established by surgical middle cerebral artery occlusion; the protein level
of PPARgamma was detected by Western blotting; the level of microRNA-383 (miR
383) was quantified by real-time PCR; the neurological outcomes were defined by
infarct volume and neurological deficits. Luciferase assay was used to identify
the luciferase activities of PPARgamma and miR-383. RESULTS: We showed here that
miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after
MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and
aggravated neurological damage. Administration of miR-383 antagomir had the
opposite effects. Furthermore, we found that PPARgamma protein was down-regulated
by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat
model of MCAO and in primary culture cells. Finally, we found that miR-383
suppressed the luciferase activity of the vector carrying the 3'UTR of PPARgamma,
whereas mutation of the binding sites relived the repressive effect of miR-383.
CONCLUSION: Our study demonstrated that miR-383 may play a key role in focal
cerebral ischemia by regulating PPARgamma expression at the post-transcriptional
level, and miR-383 may be a potential therapeutic target for stroke.
PMID- 27607023
TI - Amelioration of drought tolerance in wheat by the interaction of plant growth
promoting rhizobacteria.
AB - Drought stress adversely affects the growth and yield of wheat. The present study
was planned to investigate the effect of inoculation of plant-growth promoting
rhizobacteria (PGPR) strains IG 3 (Klebsiella sp.), IG 10 (Enterobacter ludwigii)
and IG 15 (Flavobacterium sp.) in improving drought tolerance in wheat. These
PGPR strains were screened for drought tolerance in nutrient broth supplemented
with different concentrations (0-25%) of polyethylene glycol (PEG6000). Effect of
PGPR inoculation on various physiological, biochemical parameters and gene
expression of stress responsive genes were studied under drought stress. Root
colonization at the surface and interiors of roots was demonstrated using
scanning electron microscopy (SEM) and tetrazolium staining, respectively.
Drought stress significantly affected various growth parameters, water status,
membrane integrity, osmolyte accumulation and stress-responsive gene expressions,
which were positively altered by PGPR-inoculation in wheat. Quantitative real
time (qRT)-PCR analysis revealed the up regulation of some stress-related genes
(DREB2A and CAT1) in un-inoculated wheat plants exposed to drought stress. PGPR
inoculated plants showed attenuated transcript levels suggesting improved drought
tolerance due to interaction of PGPRs. The PGPR strain IG 3 was found to be the
best in terms of influencing biochemical and physiological status of the
seedlings under drought stress. Our report demonstrates the role of PGPRs
Enterobacter ludwigii and Flavobacterium sp. in plant growth promotion of wheat
plants under drought stress. The study reports the potential of PGPR in
alleviating drought stress in wheat which could be used as potent biofertilizers.
PMID- 27607024
TI - Systemic onset juvenile idiopathic arthritis and exposure to fine particulate air
pollution.
AB - OBJECTIVES: Fine particulate matter (PM2.5) is a measurable component of ambient
pollution, and positive associations of short-term PM2.5 exposure with the
clinical presentation of systemic onset juvenile idiopathic arthritis (SJIA) in
young children have been described in a regional cohort. Our objective was to
further establish associations between short-term pollution exposures and the
reported clinical event of SJIA onset in cases residing from multiple
metropolitan regions. METHODS: A case-crossover study design was used to analyse
associations of short-term PM2.5 exposures with the event of SJIA symptom onset
from cases residing in five metropolitan regions. Time trends, seasonality,
month, and weekday were controlled for by matching. Selected exposure windows (to
14 days) of PM2.5 were examined. RESULTS: Positive, statistically significant
associations between PM2.5 concentrations and elevated risk of SJIA were not
observed. The most positive associations of short-term PM2.5 exposure with SJIA
were in children <5.5 years (RR 1.75, 95% CI 0.85-3.62). An ad hoc extended
pooled analysis including previously reported cases from Utah's metropolitan
areas identified an increased risk of SJIA for children <5.5 years (RR = 1.76,
95% CI 1.07-2.89 per 10 MUg/m3 increase in 3-day lagged moving average PM2.5).
CONCLUSIONS: In this multi-city, multi-period study small, statistically
insignificant PM2.5-SJIA associations are observed. However, as found in prior
study, the PM2.5-SJIA association is most suggestive in preschool aged children.
Larger numbers of SJIA cases spatially located in geographic areas which
experience a greater day to day ambient particulate burden may be required by the
analysis to demonstrate effects.
PMID- 27607026
TI - Phytotherapie in der Dermatologie - naturlich gut?!
PMID- 27607025
TI - Compound heterozygosity for novel splice site mutations of ITGA6 in lethal
junctional epidermolysis bullosa with pyloric atresia.
AB - Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a rare
congenital bullous disease with gastrointestinal disturbance that has been
associated with mutations in ITGA6 or ITGB4 encoding the alpha6 or beta4 subunit
of integrin, respectively. Only six ITGA6 mutations in PA-JEB have been reported
while many ITGB4 mutations have been identified, and all the ITGA6 mutations were
homozygous. Here, we report a case of lethal type PA-JEB, in which
immunofluorescence showed the lack of both alpha6 and beta4 integrins resulting
from compound heterozygous splice site mutation in ITGA6, c.387G>T and c.2506
1G>C. Maternal c.387G>T induced the skipping of the entire exon 3 and both exons
3 and 4, resulting in premature termination codon and in-frame deletion,
respectively. Paternal c.2506-1G>C caused the skipping of the exon 20 and
resulted in in-frame deletion. As a reason why the present case showed lethal
phenotype despite the in-frame deletion mutation, rapid degradation of neo
synthesized alpha6 protein and/or impaired transport of integrin were suggested
from previous reports, and the lack of localization of integrin alpha6beta4 to
the epidermal basement membrane resulted in skin fragility. Our case expands the
variety of integrin alpha6 mutations in PA-JEB.
PMID- 27607027
TI - New developments in occupational dermatology.
AB - Occupational skin diseases according to BK No. 5101 - "severe or recurrent skin
diseases which have forced the person to discontinue all occupational activities
that caused or could cause the development, worsening, or recurrence of the
disease" - is the most commonly reported notifiable occupational diseases in
Germany. Following the optimization of measures of primary, secondary, and
tertiary prevention, today most individuals affected are able to continue their
profession. With the revision of the German ordinance on occupational diseases
(BKV) in January 2015, skin cancer caused by UV irradiation was added to the list
of occupational diseases. The new occupational disease (BK) 5103 is defined as
"squamous cell carcinoma or multiple actinic keratoses of the skin caused by
natural UV irradiation". In this context, "multiple" signifies the occurrence of
either more than five individual actinic keratosis lesions over the course of 12
months or the presence of field cancerization of > 4 cm(2) . In the following
review, important aspects of this new occupational disease will be highlighted
and discussed.
PMID- 27607028
TI - Neue Entwicklungen in der Berufsdermatologie.
AB - Berufsbedingte Hautkrankheiten nach BK-Nr. 5101 stehen in Deutschland seit vielen
Jahren an der Spitze der angezeigten Berufskrankheiten. Durch die Optimierung von
Mabetanahmen der primaren, sekundaren und tertiaren Pravention konnen heutzutage
die meisten Betroffenen im Beruf verbleiben. Zum 01.01.2015 wurde die
Berufskrankheitenverordnung (BKV) novelliert und es wurde die BK-Nr. 5103
"Plattenepithelkarzinome oder multiple aktinische Keratosen der Haut durch
naturliche UV-Strahlung" als neue Berufskrankheit in die BK-Liste der BKV
aufgenommen. Die Definition von "multipel" bedeutet dabei entweder mehr als funf
einzelne aktinische Keratosen innerhalb eines Zeitraums von 12 Monaten oder das
Vorliegen einer Feldkanzerisierung von grobetaer 4 cm(2) . Wichtige Aspekte
dieser neuen Berufskrankheit werden aufgezeigt und diskutiert sowie Neuerungen
bei der BK 5101 angesprochen.
PMID- 27607029
TI - Therapeutisches Management kutaner und genitaler Warzen.
AB - Mindestens 10 % der Bevolkerung erkranken wahrend ihres Lebens an einer Infektion
mit humanen Papillomaviren (HPV), welche sich klinisch anhand der Ausbildung
kutaner oder genitaler Warzen manifestiert. Obwohl Warzen ubiquitar sind,
existieren keine definierten Behandlungen. Warzen zeigen, insbesondere in den
ersten sechs Monaten, eine erhohte Selbstheilungsrate. Dieser Umstand erschwert
die Interpretation von Studien, da haufig Patienten mit Neuinfektionen zusammen
mit Patienten mit Altinfektionen behandelt werden. Lokalisationen, Grobetae und
Dicke der Warzen sind ebenfalls in den meisten Fallen nicht berucksichtigt. Ziel
dieses Ubersichtsartikels ist eine Analyse des vorliegenden Studienmaterials,
unter der fur den klinischen Alltag so wichtigen Berucksichtigung von Subtypen
und Lokalisationen. Insbesondere die Abgrenzung zwischen frischen und chronisch
therapieresistenten Verrucae vulgares spiegelt sich in einem Therapiealgorithmus
wider. Bei genitalen Warzen wird der Therapiealgorithmus deutlicher durch das
Ausmabeta der infizierten Flache als durch das Alter der Warzen bestimmt. Bei
immunkompetenten Personen muss es mit den hier aufgezeigten therapeutischen
Methoden immer das Ziel sein, eine komplette Abheilung zu erzielen.
PMID- 27607030
TI - Therapeutic management of cutaneous and genital warts.
AB - During their lifetime, at least 10 % of the population will be infected by human
papillomaviruses (HPV), clinically characterized by the formation of cutaneous or
genital warts. Although warts are ubiquitous, there are no defined treatments.
Especially in the first six months, warts frequently resolve without therapeutic
intervention. This complicates the interpretation of study data, given that many
studies do not differentiate between newly infected patients and those with
infections that have persisted for a long time. Similarly, most studies do not
take location, size, and thickness of lesions into account, either. The objective
of the present review article is to analyze the study data currently available,
taking into consideration both subtypes and locations - factors exceedingly
crucial in clinical practice. In particular, the distinction between new-onset
and chronic recalcitrant warts is reflected in a therapeutic algorithm. In the
case of genital warts, the algorithm is more clearly determined by the extent of
the area affected rather than the longevity of lesions. In immunocompetent
individuals, any therapeutic intervention must be aimed at achieving complete
resolution.
PMID- 27607031
TI - Body dysmorphic concerns, social adaptation, and motivation for psychotherapeutic
support in dermatological outpatients.
AB - BACKGROUND AND OBJECTIVES: Dermatologists are increasingly confronted with
patients affected by body dysmorphic disorder (BDD). BDD is characterized by
excessive preoccupation with one or more perceived defect(s) or flaw(s) in
physical appearance which are not observable or appear slight to others. So far,
there have been only few studies examining the prevalence of BDD in
dermatological outpatients. In addition, the need for psychotherapeutic support
in dermatological outpatients with body dysmorphic concerns has not yet been
systematically examined. The objective of the present study was therefore to
investigate the frequency of body dysmorphic concerns as well as social
adaptation and the need for psychotherapeutic support in the aforementioned
patient group. PATIENTS AND METHODS: A total of 252 dermatological outpatients
seen at a German university hospital were consecutively enrolled, and examined
using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self
Evaluation Scale, and the German version of the University of Rhode Island Change
Assessment Scale. RESULTS: 7.9 % of all outpatients (unselected sample) showed
positive test results, suggesting clinically relevant body dysmorphic concerns.
Patients with clinically relevant body dysmorphic concerns exhibited poor social
adaptation. Contrary to expectations, these patients revealed a high motivation
for change, indicating the necessity for psychotherapeutic support. CONCLUSIONS:
Our findings confirm previous prevalence rates of BDD in dermatological
outpatients, and highlight the need for providing psychotherapeutic support to
dermatological patients.
PMID- 27607032
TI - Korperdysmorphe Symptome, soziale Anpassung und Motivation zu
psychotherapeutischer Beratung bei ambulanten dermatologischen Patienten.
AB - HINTERGRUND UND ZIELE: Die Dermatologie ist zunehmend mit Patienten konfrontiert,
die unter einer korperdysmorphen Storung (KDS) leiden. Die KDS ist gekennzeichnet
durch die ubermabetaige Beschaftigung mit einem oder mehreren wahrgenommenen
Defekten oder Makeln in der aubetaeren Erscheinung, die fur andere nicht oder
allenfalls minimal erkennbar sind. Bislang gibt es nur wenige Pravalenzstudien
bei KDS im ambulanten dermatologischen Setting. Daruber hinaus wurde die
Motivation zu psychotherapeutischer Beratung bei ambulanten dermatologischen
Patienten mit korperdysmorphen Symptomen noch nicht systematisch erfasst. Ziel
der vorliegenden Studie war daher, die Haufigkeit korperdysmorpher Symptome, die
soziale Anpassung sowie die Motivation zu psychotherapeutischer Beratung bei
ambulanten dermatologischen Patienten zu untersuchen. PATIENTEN UND METHODIK: 252
ambulante Patienten einer Universitats-Hautpoliklinik wurden konsekutiv
rekrutiert und mittels Dysmorphic Concerns Questionnaire, Soziale Aktivitat
Selbstbeurteilungs-Skala sowie Veranderungsstadien-Skala untersucht. ERGEBNISSE:
7,9 % der unselektierten Gesamtstichprobe erzielten Testresultate, die auf
klinisch relevante korperdysmorphe Symptome hinweisen. Patienten mit klinisch
relevanten korperdysmorphen Symptomen wiesen eine geringe soziale Anpassung auf.
Entgegen den Erwartungen zeigten sie eine hohe Veranderungsmotivation und Bedarf
an Psychotherapie. SCHLUSSFOLGERUNGEN: Die Ergebnisse bestatigen die bisherigen
Pravalenzraten bei KDS im ambulanten dermatologischen Setting und verdeutlichen
die Notwendigkeit psychotherapeutischer Beratungsangebote in der Dermatologie.
PMID- 27607033
TI - Mitotic rate in primary melanoma: interobserver and intraobserver reliability,
analyzed using H&E sections and immunohistochemistry.
AB - BACKGROUND: In 2009, the AJCC issued a revised melanoma staging system. In
addition to tumor thickness and ulceration, the mitotic rate was introduced as
the third major prognostic parameter for the classification of primary cutaneous
melanoma. Given that, according to the 2009 AJCC classification, the detection of
one or more dermal tumor mitoses leads to an upstaging - from stage Ia to Ib - of
melanomas with a tumor thickness of <= 1.0 mm, we set out to investigate the
reproducibility of this new parameter. METHODS: In order to assess interobserver
reliability, 17 dermatopathologists und pathologists - all well versed in the
diagnosis of cutaneous melanoma - analyzed the mitotic rate in 15 thin primary
cutaneous melanomas (mean tumor thickness 0.91 mm) using identical slides.
Mitotic rates were determined on H&E and phosphohistone H3 (Ser10)-stained
samples. Without knowledge of their previous assessment, five of the
aforementioned examiners reevaluated the samples after more than one year in
order to ascertain intraobserver reliability. RESULTS: Interobserver reliability
of the mitotic rate in thin primary melanomas is disappointing and independent of
whether H&E or immunohistochemically stained samples are used (kappa value: 0.088
[H&E], 0.154 [IH], respectively). Kappa values improved to 0.345 (H&E) and 0.403
(IH) when using a cutoff of 0/1 vs. 2+ mitoses. Similarly unsatisfactory, kappa
values for intraobserver reliability ranged from 0.18 and 0.348, depending on the
individual examiner. DISCUSSION: Given the unsatisfactory reproducibility and
large variations in assessing the mitotic rate, it remains a matter of debate
whether this diagnostic parameter should play a role in therapeutic decisions.
PMID- 27607034
TI - Mitoserate beim primaren Melanom: Interobserver- und Intraobserver
Reproduzierbarkeit am HE-Schnitt und in der Immunhistologie.
AB - HINTERGRUND: Die Melanomklassifikation wurde 2009 durch die AJCC revidiert. Fur
die Klassifizierung primarer Melanome wurde als dritte Grobetae neben Tumordicke
und Ulzeration die Angabe der Mitoserate neu eingefuhrt. Gemabeta der AJCC-2009
Klassifikation des Melanoms fuhrt der Nachweis nur einer oder mehrerer dermaler
Tumormitosen bei Melanomen <= 1,0 mm Tumordicke zu einer Umgruppierung des Tumors
von T1a nach T1b. Dies erklart, wie wichtig die Frage nach der Reproduzierbarkeit
dieses neuen Parameters ist. METHODEN: Zur Prufung der Interobserver
Reproduzierbarkeit der Mitoserate haben 17 Dermatopathologen und Pathologen, die
in der Befundung des kutanen Melanoms sehr erfahren sind, die Mitoserate in 15
dunnen Melanomen mit einer mittleren Tumordicke von 0,91 mm an demselben
Tumorschnitt bestimmt. Die Mitoserate wurde am HE-Schnitt und immunhistologisch
(IH) mittels des mitosespezifischen Antikorpers Phospho-Histon-H3 (Ser10)
bestimmt. Funf Befunder wiederholten die Bestimmung nach mehr als einem Jahr ohne
Kenntnis ihres Vorbefundes zur Ermittlung der Intraobserver-Reproduzierbarkeit.
ERGEBNISSE: Die Interobserver-Reproduzierbarkeit der Mitoserate bei dunnen
Melanomen ist unbefriedigend und unabhangig davon, ob die Mitoserate am HE
Schnitt oder am immungefarbten Schnitt bestimmt wird (kappa-Werte: 0,088 [HE]
bzw. 0,154 [IH]). Bei einer Diskriminationsschwelle von 0/1 vs. 2+ Mitosen
verbesserte sich der kappa-Wert auf 0,345 (HE) bzw. 0,403 (IH). Die Intraobserver
Reproduzierbarkeit lag mit kappa-Werten zwischen 0,18 und 0,348 je nach Befunder
ebenfalls im unbefriedigenden Bereich. DISKUSSION: Wegen der unbefriedigenden
Reproduzierbarkeit und der grobetaen Variation der Befunde zur Mitoserate bleibt
es zweifelhaft, ob dieser Befund als Grundlage fur Therapieentscheidungen
herangezogen werden kann.
PMID- 27607035
TI - Gerbstoffe aus Potentilla officinalis wirken entzundungshemmend im UV-Erythem
Test und bei Anwendung auf atopischer Haut.
AB - HINTERGRUND: Das Rhizom von Potentilla officinalis (PO) ist reich an Gerbstoffen
und wird traditionell zur aubetaerlichen Behandlung von Entzundungen der Haut und
der Schleimhaute verwendet. Ziel der vorliegenden Arbeit war die Bestatigung der
antiinflammatorischen Eigenschaften von PO mittels eines UV-Erythem-Tests und
einer klinischen Anwendungsstudie bei atopischer Haut. PROBANDEN UND METHODIK:
Die antiinflammatorische Wirkung eines PO-Extrakts (standardisiert auf 2 %
Trockensubstanz) wurde in einer prospektiven, randomisierten,
placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV-Erythem
Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer
prospektiven nicht kontrollierten Studie wurde die Wirkung und Vertraglichkeit
der 2 % PO-Creme an zwolf Erwachsenen und zwolf Kindern mit atopischer Haut nach
Anwendung uber zwei Wochen in einem definierten Testareal anhand eines Teil
SCORAD untersucht. Zusatzlich wurde die Beeinflussung der Hautrotung im Testareal
photometrisch gemessen. ERGEBNISSE: Im UV-Erythem-Test zeigte die PO-Creme eine
signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die
antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat
Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des
Teil-SCORAD und des Erythems im Testareal. Es wurden keine
Unvertraglichkeitsreaktionen beobachtet. SCHLUSSFOLGERUNGEN: PO als 2%ige
Zubereitung besitzt entzundungshemmende Eigenschaften und ist wirksam und gut
vertraglich auf atopischer Haut.
PMID- 27607036
TI - Tannins from Potentilla officinalis display antiinflammatory effects in the UV
erythema test and on atopic skin.
AB - BACKGROUND: Rich in tannins, the rhizome of Potentilla officinalis (PO) has
traditionally been used in the topical treatment of inflammatory disorders of the
skin and mucous membranes. The objective of the present study was to examine the
antiinflammatory effects of PO in the UV erythema test as well as in patients
with atopic skin. PATIENTS AND METHODS: Using the UV erythema test, the
antiinflammatory effects of a PO extract (2 %) - compared to 1 % hydrocortisone
acetate - were assessed in a randomized, prospective, placebo-controlled double
blind study of 40 healthy volunteers. In the context of a prospective non
controlled trial, the efficacy and tolerability of 2 % PO cream (applied to
defined test areas twice daily for two weeks) was evaluated in twelve adults and
twelve children with atopic skin using a partial SCORAD. In addition, the effects
on the degree of erythema in the test areas was measured photometrically.
RESULTS: In the UV erythema test, PO cream significantly reduced the erythema
index compared to the vehicle. The antiinflammatory effects of PO cream were
comparable to those of 1 % hydrocortisone acetate cream. The clinical study with
atopic patients revealed a significant reduction in the partial SCORAD as well as
erythema in the test areas. No adverse events were recorded. CONCLUSIONS: PO
cream displays antiinflammatory effects in vivo. It is effective in and well
tolerated by patients with atopic skin.
PMID- 27607037
TI - Increased risk of lung cancer in patients with eczema: a nationwide cohort study
in Taiwan.
AB - BACKGROUND: The association between lung cancer and eczema remains controversial.
Previous studies have yielded conflicting results. This retrospective population
based cohort study is aimed at clarifying the risk of lung cancer associated with
eczema. PATIENTS AND METHODS: By using the Taiwan National Health Insurance
Research Database, we identified 43,719 patients who had been newly diagnosed
with eczema in the years 2000 to 2010. The comparison cohort included 87,438
randomly selected, age-matched patients without eczema. The cases of these two
cohorts were followed until 2011. The Cox proportional hazard regression model
was used to calculate the risk of lung cancer in eczema patients. The database
did not contain any information regarding smoking, alcohol consumption,
socioeconomic status, or family history. RESULTS: After adjusting for age and
comorbidity, the population with eczema had a 2.80-fold greater risk of
developing lung cancer compared with the population in the comparison cohort
(adjusted hazard ratio 2.80, 95 % confidence interval 2.59-3.03). Eczema patients
with comorbid diseases including asthma, chronic obstructive -pulmonary disease,
alcoholic liver damage, or diabetes were at a higher risk of lung cancer compared
with the non-eczema patients without comorbidity. CONCLUSIONS: Eczema is
associated with a greater risk for the development of lung cancer. Further
studies with more comprehensive information on potential confounders are
warranted.
PMID- 27607038
TI - Erhohtes Lungenkrebs-Risiko bei Ekzempatienten: eine landesweite Kohortenstudie
in Taiwan.
AB - HINTERGRUND: Der Zusammenhang zwischen Lungenkrebs und Ekzemen bleibt umstritten.
Fruhere Studien haben zu widerspruchlichen Ergebnissen gefuhrt. Diese
retrospektive populationsbasierte Kohortenstudie zielt darauf ab, das Risiko von
Lungenkrebs im Zusammenhang mit Ekzemen abzuklaren. PATIENTEN UND METHODEN: In
der Forschungsdatenbank der taiwanesischen nationalen Krankenversicherung
identifizierten wir 43719 Patienten, bei denen in den Jahren 2000 bis 2010 ein
Ekzem neu diagnostiziert wurde. Die Vergleichskohorte bildeten 87438 zufallig
ausgewahlte, altersangepasste Patienten ohne Ekzem. Die Falle aus diesen beiden
Kohorten wurden bis 2011 verfolgt. Zur Kalkulation des Lungenkrebsrisikos bei
Ekzempatienten wurde die Cox-Regression verwendet. Die Datenbank enthielt keine
Informationen uber Raucherstatus, Alkoholkonsum, soziookonomischen Status oder
Familienanamnese. ERGEBNISSE: Nach der Bereinigung um Alter und Komorbiditat
hatte die Population mit Ekzemen ein um 2,80 erhohtes Risiko fur die Entwicklung
von Lungenkrebs gegenuber der Vergleichskohorte (bereinigte Hazard-Ratio 2,80, 95
% Konfidenzinterval 2,59-3,03). Ekzempatienten mit Begleiterkrankungen, darunter
Asthma, chronisch obstruktive Lungenerkrankungen, alkoholbedingten Leberschaden
oder Diabetes, hatten ein hoheres Lungenkrebsrisiko als Patienten ohne Ekzeme
oder Komorbiditat. SCHLUSSFOLGERUNGEN: Ekzeme gehen mit einem hoheren Risiko fur
die Entwicklung von Lungenkrebs einher. Weitere Studien mit umfassenderen
Informationen uber weitere potentielle Einflussfaktoren sind sinnvoll.
PMID- 27607039
TI - Unilasionale monosystemische kutane Langerhans-Zell-Histiozytose bei einem 11
Monate alten Kleinkind.
PMID- 27607040
TI - Unilesional, single-system cutaneous Langerhans cell histiocytosis in an 11-month
old infant.
PMID- 27607041
TI - Erfolgreiche Therapie der solaren Urtikaria mit Omalizumab.
PMID- 27607042
TI - Successful treatment of solar urticaria with omalizumab.
PMID- 27607043
TI - Kontaktallergie auf Sulfite: klinische und berufliche Relevanz - Neue Daten aus
DKG und IVDK.
PMID- 27607044
TI - Contact allergy to sulfites: clinical and occupational relevance - new data from
the German Contact Dermatitis Research Group and the Information Network of
Departments of Dermatology (IVDK).
PMID- 27607045
TI - Zehnjahriges Madchen mit subkutanen Knoten bei eosinophiler Granulomatose mit
Polyangiitis.
PMID- 27607046
TI - Eosinophilic granulomatosis with polyangiitis associated with subcutaneous
nodules in a 10-year-old girl.
PMID- 27607047
TI - Diagnosis of febrile ulceronecrotic Mucha-Habermann disease: strict clinical
criteria are imperative.
PMID- 27607048
TI - Traumatic leg ulcer caused by compression stockings due to good compliance but
poor adherence.
PMID- 27607049
TI - Ulcus cruris durch Kompressionsstrumpfe als Resultat guter Compliance aber
schlechter Adharenz.
PMID- 27607050
TI - Transiente figurierte Erytheme bei einem dreijahrigen Jungen.
PMID- 27607051
TI - Verrukose kutane und osophageale Papeln, hyperpigmentierte Beugezonen und samtige
palmare Hyperkeratose.
PMID- 27607052
TI - Verrucous cutaneous and esophageal papules, hyperpigmented flexural skin, and
velvety palmar hyperkeratosis.
PMID- 27607055
TI - Kongresskalender 2016.
PMID- 27607054
TI - Osterreichische Gesellschaft fur Dermatologie und Venerologie (OGDV).
PMID- 27607056
TI - The Ethics of Behavioral Health Information Technology: Frequent Flyer Icons and
Implicit Bias.
PMID- 27607057
TI - Factors Associated with Anemia in the Institutionalized Elderly.
AB - As a common problem in long-term care facilities (LTCFs), anemia affects 25-63%
of the elderly. The aim of the present study was to describe the prevalence and
characteristics of anemia and its associated factors in the institutionalized
elderly. The cross-sectional study was carried out with three hundred thirteen
individuals aged >= 60 years, of both genders, living in long-term care
facilities for the elderly in Salvador, Bahia, Brazil. Poisson regression (PR)
with robust variance estimates was used to assess the factors related to anemia.
The prevalence of anemia was 38%. Mild anemia was predominant in both genders
(male: 26.8%; female: 21.1%), as normocytic and normochromic anemia, with no
anisocytosis (69.75%). Anemia was associated with thinness (PR: 1.68; 95% CI:
1.04-2.72) and with moderate (PR: 1.98; 95% CI: 1.07-3.63) and total (PR: 2.61;
95% CI: 1.34-5.07) dependence in the final model. Severe dependence exhibited
borderline significance (PR: 1.94; 95% CI: 1.00-3.77). The prevalence of anemia
was high in the institutionalized elderly in both genders, with characteristics
suggesting chronic diseases as the causal factor, and the frequency of occurrence
was higher in thinness elderly with moderate to total dependence.
PMID- 27607058
TI - Survival and Surgical Outcomes for Pediatric Head and Neck Melanoma.
AB - Importance: Melanoma in children is rare, accounting for approximately 2% of all
pediatric malignant neoplasms. However, for the past 30 years, the incidence of
melanoma in those younger than 20 years has been increasing. Location of the
primary tumor has been shown to be an important prognostic factor, with melanomas
of the scalp and neck conferring a worse prognosis than those originating at
other sites. Objective: To examine the survival, demographic, tumor, and
treatment characteristics of pediatric head and neck melanoma. Design, Setting,
and Participants: We performed a retrospective cohort study using information
from the National Cancer Data Base from January 1, 1998, to December 31, 2012, on
pediatric (<=18 years) and adult (>18 years) patients with head and neck
melanoma. Data analysis was conducted from August 1, 2015, to June 30, 2016.
Exposure: Pediatric age (<=18 years) at diagnosis of head and neck melanoma. Main
Outcomes and Measures: Survival differences were estimated using a Cox
proportional hazards regression model. Surgical outcomes, including nodal
sampling and margin status, were estimated with generalized linear models
comparing pediatric and adult patients. Patient demographic, tumor, and treatment
characteristics were estimated using t tests and chi2 tests between pediatric and
adult patients with head and neck melanoma for continuous and categorical data,
respectively. Results: Of the 84 744 patients with head and neck melanoma, 657
(0.8%) were 18 years or younger (mean [SD] age, 13.5 [4.7] years; 285 female and
372 male; 610 white). Pediatric and adult patients had similar demographics but
different histologic subtypes (risk difference of pediatric vs adult patients:
melanoma, not otherwise specified, 8.5% [95% CI, 4.7%-12.3%]; superficial
spreading, 4.2% [95% CI, 0.89%-7.4%]; and lentigo maligna, -13.4% [95% CI, -14.1%
to 12.6%]). Pediatric patients had tumors of similar mean depth to those in adult
patients (pediatric, 1.54 mm; adult; 1.39 mm; absolute difference, 0.15 mm; [95%
CI, -0.32 to 0.008]) and more frequent nodal metastases than did adult patients
(risk difference of pediatric vs adult patients for stage T2, 23.9% [95% CI,
14.1%-33.6%]). Five-year survival among pediatric patients was higher for those
with stage 1, 2, or 3 disease (absolute difference of pediatric vs adult
patients: stage 1, 18% [95% CI, 9.7%-26.3%]; stage 2, 36% [95% CI, 25.3%-46.7%];
stage 3, 39% [95% CI, 26.8%-51.2%]; and stage 4, 2% [95% CI, -8.2% to 12.2%]).
Conclusions and Relevance: Although pediatric patients with head and neck
melanoma present with similar tumor depth and more frequent nodal metastases than
do adult patients, younger patients have higher overall survival.
PMID- 27607059
TI - Catalyst-Free Rearrangement of Allenyl Aryldiazoacetates into 1,5-Dihydro-4H
pyrazol-4-ones.
AB - Phenylpropargyl diazoacetates exist in equilibrium with 1-phenyl-1,2-dien-1-yl
diazoacetate - allenes that are rapidly formed at room temperature through 1,3
acyloxy migration catalyzed by gold(I) or gold(III) compounds, and these
catalysts react solely with the pi-donor rather than with the diazo group. The
product allene of the aryldiazoacetates undergoes rearrangement that is not
catalyzed by gold in which the terminal nitrogen of the diazo functional group
adds to the central carbon of the allene, initiating a sequence of bond-forming
reactions, resulting in the production of 1,5-dihydro-4H-pyrazol-4-ones in good
yields. These 1,5-dihydro-4H-pyrazol-4-ones undergo intramolecular 1,3-acyl
migration to form an equilibrium mixture and can quantitatively transfer the acyl
group to an external nucleophile with formation of 4-hydroxypyrazoles. Reactions
of phenylpropargyl phenyldiazoacetates catalyzed by cationic gold complexes are
initiated at the diazo functional group to form a gold carbene whose subsequent
cascade process (intramolecular addition, then aromatic substitution) results in
the formation of a product that is uniquely characteristic of this pathway.
PMID- 27607060
TI - Copper Antimonide Nanowire Array Lithium Ion Anodes Stabilized by Electrolyte
Additives.
AB - Nanowires of electrochemically active electrode materials for lithium ion
batteries represent a unique system that allows for intensive investigations of
surface phenomena. In particular, highly ordered nanowire arrays produced by
electrodeposition into anodic aluminum oxide templates can lead to new insights
into a material's electrochemical performance by providing a high-surface-area
electrode with negligible volume expansion induced pulverization. Here we show
that for the Li-CuxSb ternary system, stabilizing the surface chemistry is the
most critical factor for promoting long electrode life. The resulting solid
electrolyte interphase is analyzed using a mix of electron microscopy, X-ray
photoelectron spectroscopy, and lithium ion battery half-cell testing to provide
a better understanding of the importance of electrolyte composition on this
multicomponent alloy anode material.
PMID- 27607061
TI - Tau Tubulin Kinase TTBK2 Sensitivity of Glutamate Receptor GluK2.
AB - BACKGROUND/AIMS: Inherited, autosomal dominant spinocerebellar ataxia type 11
(SCA11) is caused by loss of function mutations of TTBK2 (tau tubulin kinase 2).
Mutations observed in patients with SCA11 include truncated TTBK2(450). The
present study explored the possibility that TTBK2 influences the function of the
glutamate receptor GluK2. METHODS: GluK2 was expressed in Xenopus oocytes without
and with additional expression of wild type TTBK2, the truncated mutant
TTBK2(450), or the kinase dead mutants TTBK2(KD) and TTBK2(450/KD). GluK2 current
was determined by dual electrode voltage clamp and GluK2 protein abundance in the
cell membrane utilizing confocal microscopy. RESULTS: Glutamate exposure of GluK2
expressing oocytes generated a current, which was significantly lower in oocytes
expressing GluK2 together with TTBK2 wt or TTBK2(KD) than in oocytes expressing
GluK2 alone or together with either TTBK2(450) or TTBK2(450/KD). According to
confocal microscopy of EGFP-tagged GluK2, TTBK2 wt decreased the GluK2 protein
abundance in the cell membrane. Overexpression of an inactive RAB5(N133I) mutant
but not RAB5wt could reverse the TTBK2 effect on GluK2 suggesting that RAB5
function is required for the effect. CONCLUSIONS: TTBK2 down-regulates GluK2
activity by decreasing the receptor protein abundance in the cell membrane via
RAB5-dependent endocytosis, an effect that may protect against
neuroexcitotoxicity.
PMID- 27607062
TI - Cannabis for Cognitive Enhancement as a New Coping Strategy? Results From a
Survey of Students at Four Universities in Germany.
AB - BACKGROUND: Cognitive Enhancement (CE) is often discussed in relation to
stimulant drugs, such as amphetamines (AMPH). However, there is some evidence
that cannabis (CAN) can be used for CE. OBJECTIVE: This study compares the
knowledge, prevalence, and perceived effects of and factors associated with the
knowledge of or use of CAN versus AMPH for CE among undergraduate students at
four German universities. METHODS: A survey was taken of 1,538 students at four
German universities. It investigated their knowledge and use of CAN and AMPH for
CE as well as associated factors. Descriptive and analytic (Mann-Whitney-U test,
Fisher's exact test, logistic regression) statistics were obtained using SPSS.
RESULTS: Responses were obtained from 1,026 participants (57.2%) at three
universities from the Universitatsallianz Metropole Ruhr (UAR) (Bochum, Dortmund,
Duisburg-Essen) and 512 respondents (68.3%) in Mainz. We observed lifetime
prevalence rates of 3.5% for the use of CAN and 2.1% for the use of AMPH for the
purpose of CE. CAN users perceived pressure to perform as more of a burden than
AMPH users (mean: 3.2, CAN users: 4.7, AMPH: 2.9; p =.042). CAN users used the
substances for studying for exams significantly less often than AMPH users (p
=.025), and CAN users perceived less of an enhancing effect of the drug compared
to AMPH users (p <.001). CONCLUSIONS: A considerable number of students report
having used CAN for CE. However, our research indicates differences in
perceptions and experiences of CE between CAN and AMPH users. Further research on
the role of CAN for CE and conceptual analyses to differentiate between different
understandings of CE are warranted.
PMID- 27607064
TI - Correction: First Case of Legionnaire's Disease Caused by Legionella anisa in
Spain and the Limitations on the Diagnosis of Legionella non-pneumophila
Infections.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159726.].
PMID- 27607063
TI - The Influence of 2-Year Changes in Physical Activity, Maturation, and Nutrition
on Adiposity in Adolescent Youth.
AB - The aim of this longitudinal study was to explore temporal patterns of physical
activity (PA) and adiposity in Spanish adolescents. Eighty healthy adolescents
were followed over a 2-year period (42 girls and 38 boys). A PA score was
estimated using the Physical Activity Questionnaire for Adolescents (PAQ-A).
Adiposity was assessed by anthropometric measurements; body mass index (BMI) and
fat mass percent (FMP) were calculated using standard equations. Sexual maturity
was estimated by percentage of predicted adult stature. Dietary intake was
assessed by a self-administered food-frequency questionnaire. Three assessments
were performed: September 2011 (S1), 2012 (S2), and 2013 (S3). A repeated
measures ANOVA was conducted to examine temporal changes in PA and FMP and sex
change in maturation categories (two factor mixed-design, 2x2x3). A stepwise
linear regression was conducted in order to estimate the predictors of FMP
change. Significant changes for FMP were found between S1, S2, and S3 (23.41+/
8.24 vs. 21.89+/-7.82 vs. 22.05+/-8.06, p<0.05; respectively); a significant
interaction of FMP with sex was observed (F = 4.387, p<0.05 for S2-S3), but not
for maturation. PA at S2 was significantly higher than S3 (2.58+/-0.72 vs. 2.29+/
0.73, p<0.001). An interaction between PA change and sex was statically
significant (F = 4.889, p<0.05 for S2-S3). A reduction in PA was observed after
the S2 period without changes in adiposity. In contrast, a significant reduction
in FMP was seen between S1 and S2, while PA did not significantly change. There
were no significant differences for nutritional variables between S1 and S3, and
nutrition was not a determinant of the changes in PA or FMP. Our results suggest
that body composition changes observed during adolescence are not driven by
changes in PA. Moreover, the interaction analysis suggests that PA behavior is
affected by sex, but is not modified by maturation.
PMID- 27607066
TI - [Interests and Conflicts of Interest].
PMID- 27607065
TI - Virulence factors and antimicrobial resistance in Escherichia coli strains
isolated from hen egg shells.
AB - Eggs may contain extraintestinal pathogenic (ExPEC) and diarrheogenic (DEC)
Escherichia coli which in addition may carry antibiotic resistance. The wide use
of biocides and disinfectants in the food industry may induce biocide tolerance
in bacteria. The aim of the present study was to evaluate biocide tolerance and
antibiotic resistance in E. coli from hen egg shells. A total of 27 isolates
obtained from a screening of 180 eggs were studied. Seven isolates carried both
eae and bfpA genes of typical enteropathogenic E. coli (EPEC) strains, while 14
isolates only carried eae associated with atypical EPEC strains. Shiga toxin
genes stx and stx2 were detected in four isolates. Heat-stable and heat-labile
enterotoxin genes as well as aggR were also detected. Several isolates had
minimum inhibitory concentrations (MICs) that were higher than the wild-type for
the biocide hexadecylpyridinium chloride (HDP, 18.52%) or the commercial
disinfectant P3 oxonia (OX, 14.81%). Antibiotic resistance was detected for
ampicillin (37.03%), streptomycin (37.03%), tetracycline (37.03%),
chloramphenicol (11.11%), nalidixic acid (18.51%) and trimethoprim
sulfamethoxazole (14.81%). Eight isolates (29.63%) were biocide tolerant and
antibiotic resistant. Efflux pump genes detected included acrB (96.29%), mdfA
(85.18%) and oxqA (37.03%), in addition to quaternary ammonium compound (QAC)
resistance genes qacA/B (11.11%) and qacE (7.40%). Antibiotic resistance genes
detected included blaCTX-M-2 (22.22%), blaTEM (3.70%), blaPSE (3.70%), tet(A)
(29.63%), tet(B) (29.63%), tet(C) (7.40%), tet(E) (11.11%), aac(6')-Ib (3.70%),
sul1 (14.81%), dfrA12 (3.70%) and dfrA15 (3.70%). Most isolates (96.30%) carried
more than one genetic determinant of resistance. The most frequent combinations
were efflux pump components acrB and mdfA with tetracycline resistance genes
(33.33% of isolates). Isolates carrying QAC resistance genes also carried between
4 and 8 of the additional antimicrobial resistance genes investigated. Regardless
of biocide tolerance and antibiotic resistance, all isolates were sensitive to
carvacrol (0.25%), thymol (0.125%) and trisodium phosphate (1 to 1.5%), but they
exhibited a heterogeneous response to sodium lactate and lysozyme-EDTA
combinations that apparently were not related with antibiotic resistance. Results
from the study reveal not only a low incidence of biocide tolerance but also the
presence of multiple resistance strains carrying multiple genetic determinants of
resistance.
PMID- 27607067
TI - [Sporadic Cerebral Amyloid Angiopathy: An Overview with Clinical Cases].
AB - Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in
the elderly. Neuropathologically, it is characterized by deposition of amyloid
beta (Abeta) in the wall of small to medium-sized arteries, capillaries and
venules of the cerebral cortex and leptomeninges. Over the last years it was
recognized as an important cause of spontaneous intracerebral hemorrhage and
cognitive deficits in the elderly. The clinical and radiological manifestations
are diverse ranging from acute onset focal neurological deficits due to
intracerebral lobar hemorrhage to subacute progressive cognitive impairment due
to Abeta-mediated inflammation confluent subcortical edema. The wide clinico
radiological spectrum of CAA is a major challenge for the neurologist and stroke
physician. This review provides a structured and detailed look at recent
developments in CAA, and is illustrated with case studies.
PMID- 27607068
TI - [Treatment Options for Executive Dysfunction].
AB - The concept of executive function is a so-called umbrella concept, so that it
includes many different and in some cases mutually contradictory higher-level
organizational abilities such as planning, monitoring, inhibition and control of
action. Typically, the cause of an executive dysfunction is an underlying lesion
in the prefrontal cortex or subcortical regions. Deficits in executive functions
appear in the fields of cognition as well as behavior. Diagnosis requires the use
of a wide-ranging repertoire of tests and questionnaires making it a time
consuming process. Different therapeutic approaches addressing the diverse
symptoms of executive dysfunction, both positive and negative, are available.
These include modification and manipulation of the environment and practice of
cognitive repetitive procedures. The former are implemented particularly in cases
of severely impaired persons. The latter are used in persons in whom cognitive
dysfunctions are the dominating symptoms of the disorder.The operational area of
therapeutic approaches using paper and pencil as well as computer programs limits
them to treatment of cognitive dysfunction. If behavioral disturbances dominate
the clinical picture, other procedures should be used.The effectiveness of
cognitive therapy of executive dysfunction is well demonstrated according to the
criteria of evidence-based medicine (EBM).
PMID- 27607069
TI - [Peripheral Nerve Injuries in Sports].
AB - Peripheral nerve injuries due to sports are relatively rare but the exact
incidence is not known due to a lack of epidemiological studies. Particular
sports activities tend to cause certain peripheral nerve injuries including
direct acute compression or stretching, repetitive compression and stretching
over time, or another mechanism such as ischemia or laceration. These nerve
lesions may be severe and delay or preclude the athlete's return to sports,
especially in cases with delayed diagnosis. Repetitive and vigorous use or
overuse makes the athlete vulnerable to disorders of the peripheral nerves, and
sports equipment may cause compression of the nerves. Depending on etiology, the
treatment is primarily conservative and includes physiotherapy, modification of
movements and sports equipment, shoe inserts, splinting, antiphlogistic drugs,
sometimes local administration of glucocorticoids or, lately, the use of
extracorporeal shock waves. Most often, cessation of the offending physical
activity is necessary. Surgery is only indicated in the rare cases of direct
traumatic nerve injury or when symptoms are refractory to conservative therapy.
Prognosis mainly depends on the etiology and the available options of modifying
measures.This article is based on the publications "Reuter I, Mehnert S.
Engpasssyndrome peripherer Nerven bei Sportlern". Akt Neurol 2012;39:292-308 and
Sportverl Sportschad 2013;27:130-146.
PMID- 27607070
TI - [Efficacy of Epileptological Consultation After Initially Unsuccessful
Antiepileptic Medication].
AB - OBJECTIVE: At least 25 % of patients with epilepsy do not achieve seizure freedom
with their first antiepileptic medication. The aim of this study is to make a
contribution to discussions on the efficacy of further antiepileptic medications
in achieving seizure freedom for at least one year or reduction of seizure
frequency of more than 50 % for more than one year. METHODS: All patients who
presented between January 1, 2009 and July 1, 2013 to the epileptological
outpatient consulting service of the University of Rostock with at least one
seizure in the previous year despite taking at least one antiepileptic medication
were evaluated. Outcome was assessed according to the data available on July 1,
2014. RESULTS: 70 patients (35 f/35 m) aged 43.6 years on average (SD 16.7) with
active epilepsy, who had taken 3.7 antiepileptic drugs on average (SD 2.8) before
the first presentation to our service, were counseled on further antiepileptic
treatment options. On average, 1.96 (SD 1.8) antiepileptic drugs were introduced
in the therapy. At the last visit to our service, 15.7 % of the patients were
seizure free for more than one year and 45,6 % of the patients had a reduction of
seizure frequency of at least more than 50 %. CONCLUSION: With specialized
epileptological counseling, substantial improvement in seizure frequency can be
achieved in about 60 % of patients with epilepsy after failure of the initial
antiepileptic drug.
PMID- 27607071
TI - [Aeromedical Decision-Making in Psychiatry].
AB - This paper reviews aeromedical decision-making in psychiatry. It explains the
"one-percent rule", the general medical criteria for fitness for flying and how
they are applied to psychiatric disorders.
PMID- 27607073
TI - [Not Available].
PMID- 27607072
TI - [Diagnosis and Therapeutic Interventions in Autism Spectrum Disorders in
Adulthood].
AB - Autism spectrum disorders (ASD) are characterized by disturbed social interaction
and communication as well as stereotyped or repetitive behaviors and interests.
Although adults with ASD often acquire complex compensatory strategies that help
them master social situations in a rule-based fashion, they still show
impairments in intuitive processing of social signals and especially nonverbal
communication in complex everyday situations. This constitutes a particular
challenge for the psychotherapy of ASD. Psychotherapists are required to
explicitly inform and act as an agent of the non-autistic world to enable
patients to acquire the ability to take different perspectives. The overall aim
of cognitive behavioral therapy interventions addressing ASD in adulthood is to
extend the patients' behavioral repertoire to improve their quality of life.
Thus, besides psychoeducation on ASD and its frequently associated comorbidities,
psychotherapy for adults with ASD should focus on the training and development of
social-communicative skills. Furthermore, dealing with stress in everyday
situations is an important aspect of psychotherapy of these patients.
PMID- 27607075
TI - Introduction to a Special Issue of JA&WMA on NOAA's 7th International Workshop on
Air Quality Forecasting Research (IWAQFR).
PMID- 27607074
TI - The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins
to Aldolase Is Enhanced by Phosphorylation.
AB - Aldolase has been implicated as a protein coupling the actomyosin motor and cell
surface adhesins involved in motility and host cell invasion in the human malaria
parasite Plasmodium falciparum. It binds to the cytoplasmic domain (CTD) of type
1 membrane proteins of the thrombospondin-related anonymous protein (TRAP)
family. Other type 1 membrane proteins located in the apical organelles of
merozoites, the form of the parasite that invades red blood cells, including
apical membrane antigen 1 (AMA1) and members of the erythrocyte binding ligand
(EBL) and reticulocyte binding homologue (RH) protein families have been
implicated in host cell binding and invasion. Using a direct binding method we
confirm that TRAP and merozoite TRAP (MTRAP) bind aldolase and show that the
interaction is mediated by more than just the C-terminal six amino acid residues
identified previously. Single amino acid substitutions in the MTRAP CTD abolished
binding to aldolase. The CTDs of AMA1 and members of the EBL and RH protein
families also bound to aldolase. MTRAP competed with AMA1 and RH4 for binding to
aldolase, indicating overlapping binding sites. MTRAP CTD was phosphorylated in
vitro by both calcium dependent kinase 1 (CDPK1) and protein kinase A, and this
modification increased the affinity of binding to aldolase by ten-fold.
Phosphorylation of the CTD of members of the EBL and RH protein families also
increased their affinity for aldolase in some cases. To examine whether or not
MTRAP expressed in asexual blood stage parasites is phosphorylated, it was tagged
with GFP, purified and analysed, however no phosphorylation was detected. We
propose that CTD binding to aldolase may be dynamically modulated by
phosphorylation, and there may be competition for aldolase binding between
different CTDs. The use and efficiency of alternate invasion pathways may be
determined by the affinity of adhesins and cell invasion proteins for aldolase,
in addition to their host ligand specificity.
PMID- 27607076
TI - Effect of Putrescine Treatment on Chilling Injury, Fatty Acid Composition and
Antioxidant System in Kiwifruit.
AB - We investigated the effects of different concentrations (0, 1, 2 and 4 mM) of
putrescine on chilling injury, fruit quality, ethylene production rate, fatty
acid composition and the antioxidant system of cold-stored kiwifruit (Actinidia
chinensis Planch. var. chinensis 'Hongyang'). We achieved a significant decrease
in ethylene production, maintained fruit quality and alleviated chilling injury
during storage via treatment with 2 mM putrescine. Furthermore, putrescine
treatment inhibited increases in superoxide anion production rate and H2O2
concentration, while maintaining higher membrane lipid unsaturation as well as
increased activities of superoxide dismutase and catalase. In addition,
putrescine treatment enhanced the activities of antioxidant enzymes related to
the ascorbate-glutathione cycle while causing higher levels of ascorbic acid and
reduced glutathione. Our results suggest that induced tolerance against chilling
injury via putrescine treatment in cold-stored kiwifruit may be due to enhanced
antioxidant activity, increased unsaturation of membrane lipids, and inhibited
ethylene production.
PMID- 27607077
TI - Computational approaches to investigating allostery.
AB - Allosteric regulation plays a key role in many biological processes, such as
signal transduction, transcriptional regulation, and many more. It is rooted in
fundamental thermodynamic and dynamic properties of macromolecular systems that
are still poorly understood and are moreover modulated by the cellular context.
Here we review the computational approaches used in the investigation of
allosteric processes in protein systems. We outline how the models of allostery
have evolved from their initial formulation in the sixties to the current views,
which more fully account for the roles of the thermodynamic and dynamic
properties of the system. We then describe the major classes of computational
approaches employed to elucidate the mechanisms of allostery, the insights they
have provided, as well as their limitations. We complement this analysis by
highlighting the role of computational approaches in promising practical
applications, such as the engineering of regulatory modules and identifying
allosteric binding sites.
PMID- 27607078
TI - Is a single question of the Global Physical Activity Questionnaire (GPAQ) valid
for measuring sedentary behaviour in the Chilean population?
AB - A study was conducted to assess the validity of the Global Physical Activity
Questionnaire (GPAQ) for measuring sedentary behaviour (SB) in the Chilean adult
population. About 217 adults (93/124 male/female, 43.8 +/- 15.75 years) who were
randomly selected during National Health Survey 2009-2010 completed the protocol.
The participants wore an ActiGraph GT3X (AG) for 7 consecutive days and then
completed the GPAQ (single-item question for measuring time spent sitting in a
usual day). Validity was examined using Spearman's correlation, mean bias and
limits of agreement (LoA), with AG (vertical axis <100 counts . min-1) as the
reference standard for estimates of SB in bouts of 1 (AG1), 5 (AG5) and 10 (AG10)
min. Agreement between the GPAQ and AG for classifying data into quartiles and
tertiles was assessed with kappa method. The GPAQ showed fair correlation with
AG1, AG5 and AG10 (range = 0.23-0.26), with large mean biases (range = -293.9,
76.12 min . day-1). Agreement between the GPAQ and AG1, AG5 and AG10 was poor for
categorising time spent in SB into tertiles and quartiles. The single question
from the GPAQ has shown fair validity for measuring SB and poor ability for
correctly classifying individuals into tertiles or quartiles of SB in a Chilean
population.
PMID- 27607079
TI - Imaging latex-carbon nanotube composites by subsurface electrostatic force
microscopy.
AB - Electrostatic modes of atomic force microscopy have shown to be non-destructive
and relatively simple methods for imaging conductors embedded in insulating
polymers. Here we use electrostatic force microscopy to image the dispersion of
carbon nanotubes in a latex-based conductive composite, which brings forth
features not observed in previously studied systems employing linear polymer
films. A fixed-potential model of the probe-nanotube electrostatics is presented
which in principle gives access to the conductive nanoparticle's depth and
radius, and the polymer film dielectric constant. Comparing this model to the
data results in nanotube depths that appear to be slightly above the film-air
interface. This result suggests that water-mediated charge build-up at the film
air interface may be the source of electrostatic phase contrast in ambient
conditions.
PMID- 27607080
TI - What are clinical ethics advisory groups for?
PMID- 27607081
TI - Clinical ethics support services in New Zealand-tailoring services to meet the
needs of doctors.
AB - AIMS: To better understand senior doctors' attitudes to clinical ethics support
services at Capital and Coast District Health Board (CCDHB), in order to better
tailor clinical ethics support services in New Zealand to the needs of doctors.
METHODS: We conducted in-depth semi-structured interviews with 14 senior doctors
at CCDHB in 2011 and 2012. Data analysis was inductive and iterative. RESULTS:
Doctors primarily rely on informal avenues of peer consultation for support when
making difficult ethical decisions. Many participants saw a potential role for
formal ethics support, but expressed concern about how ethics support services
would fit into their clinical practice. Primary concerns included the
accessibility of support services and moral responsibility for ethical decision
making in clinical settings. CONCLUSIONS: Doctors are more willing to engage in
ethics support services where they are able to participate in, or at least
observe, the decision-making process.
PMID- 27607082
TI - Socioeconomic correlates of quality of life for non-Maori in advanced age: Te
Puawaitanga o Nga Tapuwae Kia ora Tonu. Life and Living in Advanced Age: a Cohort
Study in New Zealand (LiLACS NZ).
AB - AIM: To establish socioeconomic and cultural profiles and correlates of quality
of life (QoL) in non-Maori of advanced age. METHOD: A cross sectional analysis of
the baseline data of a cohort study of 516 non-Maori aged 85 years living in the
Bay of Plenty and Rotorua areas of New Zealand. Socioeconomic and cultural
characteristics were established by face-to-face interviews in 2010. Health
related QoL (HRQoL) was assessed with the SF-12. RESULTS: Of the 516 non-Maori
participants enrolled in the study, 89% identified as New Zealand European, 10%
other European, 1% were of Pacific, Asian or Middle Eastern ethnicity; 20% were
born overseas and half of these identified as 'New Zealand European.' More men
were married (59%) and more women lived alone (63%). While 89% owned their own
home, 30% received only the New Zealand Superannuation as income and 22% reported
that they had 'just enough to get along on'. More than 85% reported that they had
sufficient practical and emotional support; 11% and 6% reported unmet need for
practical and emotional support respectively. Multivariate analyses showed that
those with unmet needs for practical and emotional support had lower mental HR
QoL (p<0.005). Reporting that family were important to wellbeing was associated
with higher mental HR QoL (p=0.038). Those that did not need practical help
(p=0.047) and those that reported feeling comfortable with their money situation
(0.0191) had higher physical HRQoL. High functional status was strongly
associated with both high mental and high physical HR QoL (p<0.001). CONCLUSION:
Among our sample of non-Maori people of advanced age, those with unmet support
needs reported low HRQoL. Functional status was most strongly associated with
mental and physical HRQoL.
PMID- 27607083
TI - Adherence to the current guidelines for bradycardic pacing in the octogenarian
and nonagenarian populations.
AB - AIM: A significant proportion of single-chamber ventricular pacemakers are
implanted in octogenarian and nonagenarian patients. We aimed to assess whether
the current pacing guideline is adhered for these populations. METHODS: We
retrospectively identified patients >=80 years of age, who received their first
pacemaker from July 2010 to June 2013. RESULTS: A total of 356 patients were
identified. Mean age was 86.1 years and 82.6 years for single and dual-chamber
pacemakers respectively (p<0.05). Total procedure-related complications occurred
in 9.5% and were comparable between both groups (p=0.08). At the time of
implantation, 185 patients who received single-chamber pacemaker were in sinus
rhythm (52%). They were older (86.2+/-4.3 vs 82.6+/-2.9, p<0.05), more likely to
have ischaemic and valvular heart disease (68 vs 27, p= 0.02 and 22 vs 13,
p=0.01, respectively), and cognitive impairment (34 vs 0, p= 0.001). They were
also more likely to be discharged to a residential care facility (17 vs 1,
p<0.01). CONCLUSION: The utility of dual-chamber pacemaker in this age group
remains below expectation and did not comply with current cardiac pacing
guidelines. The presence of older age, multiple co-morbidities, cognitive
impairment and residential care on discharge likely influenced the type of device
implanted.
PMID- 27607084
TI - Protecting New Zealand children from exposure to the marketing of unhealthy foods
and drinks: a comparison of three nutrient profiling systems to classify foods.
AB - AIM: Promotion of unhealthy foods and drinks is a significant, modifiable risk
factor for child obesity and diet-related non-communicable diseases. We compared
three accepted nutrient profiling systems: the Health Star Rating (HSR), the
Ministry of Health Food and Beverage Classification System (FBCS) and the World
Health Organization (WHO) Regional Office for Europe Nutrient Profiling Model, to
identify the best system to protect New Zealand children from exposure to the
marketing of unhealthy foods and beverages. METHODS: 13,066 packaged foods from
the 2014 New Zealand Nutritrack database were classified as 'restricted' or 'not
restricted' as per the WHO model; 'everyday/sometimes' or 'occasional' as per the
FBCS model; and '<3.5 stars' or '>=3.5 stars' as per the HSR model. The
proportion and types of packaged foods that met the criteria for all three
systems or none of the systems, and the types of food products classified as
'restricted' under the WHO model but classified as 'everyday/sometimes' (FBCS
model) or as having >3.5 stars, were determined. RESULTS: Under any of the three
nutrient profiling systems, approximately one-third (29-39%) of New Zealand
packaged foods would be permitted to be marketed to children. The WHO Model would
permit marketing of 29% of products; the HSR system would permit 36%; and the
FBCS system would permit 39%. The WHO Model restricts marketing of unhealthy
foods more effectively than the other two systems. The HSR and FBCS systems would
permit marketing of a number of food products of concern, particularly high-sugar
breakfast cereals, fruit juices and ready meals. CONCLUSION: The WHO Regional
Office for Europe Nutrient Profiling Model should underpin the Advertising
Standards Authority revised Children's Code for Advertising Food. The
effectiveness of the new Code in reducing New Zealand children's exposure to
marketing of unhealthy foods and drinks should be subject to evaluation by an
independent body.
PMID- 27607085
TI - What's new with the flu? Reflections regarding the management and prevention of
influenza from the 2nd New Zealand Influenza Symposium, November 2015.
AB - Influenza is a common respiratory viral infection. Seasonal outbreaks of
influenza cause substantial morbidity and mortality that burdens healthcare
services every year. The influenza virus constantly evolves by antigenic drift
and occasionally by antigenic shift, making this disease particularly challenging
to manage and prevent. As influenza viruses cause seasonal outbreaks and also
have the ability to cause pandemics leading to widespread social and economic
losses, focused discussions on improving management and prevention efforts is
warranted. The Immunisation Advisory Centre (IMAC) hosted the 2nd New Zealand
Influenza Symposium (NZiS) in November 2015. International and national
participants discussed current issues in influenza management and prevention.
Experts in the field presented data from recent studies and discussed the ecology
of influenza viruses, epidemiology of influenza, methods of prevention and
minimisation, and experiences from the 2015 seasonal influenza immunisation
campaign. The symposium concluded that although much progress in this field has
been made, many areas for future research remain.
PMID- 27607086
TI - Improved compliance with the World Health Organization Surgical Safety Checklist
is associated with reduced surgical specimen labelling errors.
AB - AIMS: A new approach to administering the surgical safety checklist (SSC) at our
institution using wall-mounted charts for each SSC domain coupled with migrated
leadership among operating room (OR) sub-teams, led to improved compliance with
the Sign Out domain. Since surgical specimens are reviewed at Sign Out, we aimed
to quantify any related change in surgical specimen labelling errors. METHODS:
Prospectively maintained error logs for surgical specimens sent to pathology were
examined for the six months before and after introduction of the new SSC
administration paradigm. We recorded errors made in the labelling or completion
of the specimen pot and on the specimen laboratory request form. Total error
rates were calculated from the number of errors divided by total number of
specimens. Rates from the two periods were compared using a chi square test.
RESULTS: There were 19 errors in 4,760 specimens (rate 3.99/1,000) and eight
errors in 5,065 specimens (rate 1.58/1,000) before and after the change in SSC
administration paradigm (P=0.0225). CONCLUSIONS: Improved compliance with
administering the Sign Out domain of the SSC can reduce surgical specimen errors.
This finding provides further evidence that OR teams should optimise compliance
with the SSC.
PMID- 27607087
TI - The uses of mental health telephone counselling services for Chinese speaking
people in New Zealand: demographics, presenting problems, outcome and evaluation
of the calls.
AB - AIM: This study aimed to investigate the call profiles of a Chinese-speaking
mental health counselling helpline service in New Zealand (Chinese Lifeline
provided by Lifeline Aotearoa) and to evaluate the calls and explore the possible
factors influencing the outcome of the calls. METHOD: A random sample of 151
answered calls was involved. Descriptive analysis with appropriate statistical
tests was used to analyse the client profile and outcome data. RESULTS: The
majority of the calls were made by female callers, aged between 21-60 both single
and married. Top three presenting problems were: 1) mental health issues (82.1%);
2) family/partner relationship issues (47.0%) and 3) communication and related
difficulties (45.0%). The majority of the calls (65%) ended after a clear
decision in overcoming the issues made by the caller, with the help from the
counsellor. Discussing mental health issues, grief and loss issues, and
communication and related difficulties were shown to have influenced length of
calls (p<0.05). Caller's age, frequency of calls, discussing relationship
problems with family/partner, and physical problems were shown to have influenced
the helpline counsellors' satisfaction of the helpfulness of the calls (p<0.05).
CONCLUSION: The service receives calls from callers with a wide range of
demographics and a large variety of presenting issues. This study identified
several important factors which influenced counsellors' satisfaction of the calls
and the length of the calls.
PMID- 27607088
TI - Overview of the 2015 American Thyroid Association guidelines for managing thyroid
nodules and differentiated thyroid cancer.
AB - The last few years have witnessed numerous publications addressing the management
of thyroid nodules and differentiated thyroid cancers. The purpose of this review
is to provide a simplified summary of the newly released guidelines by the
American Thyroid Association. A systematic approach has been recommended to
evaluate a thyroid nodule through clinical assessment, measurement of serum
Thyroid Stimulating Hormone, neck ultrasonography and Fine Needle Aspiration
where appropriate. This is followed by cytology analysis using the Bethesda
scoring system to detect malignancy. Once diagnosed, thyroid cancers need to be
staged and risk stratification needs to be applied to develop further treatment
plans. Lastly, several recommendations have been presented to assure proper
follow-up and support for thyroid cancer patients regardless of the treatment
received.
PMID- 27607089
TI - Amniotic fluid embolism after intrauterine fetal demise.
AB - We present a case of the successful treatment of severe amniotic fluid embolism
in a 41-year-old woman undergoing emergency caesarean section at 36 weeks of
gestation for placental abruption and intrauterine fetal demise. The treatment
included prolonged cardiopulmonary resuscitation, emergency hysterectomy, re
operation with intra-abdominal packing and intra-aortic balloon pump insertion.
The patient made a remarkable recovery and to date has minimal residual
morbidity. Amniotic fluid embolism syndrome (AFES) is a rare and often fatal
obstetric condition that remains one of the main causes of maternal mortality in
developed countries. The incidence varies from 2 to 6 per 100,000 and suggested
mortality rates exceed 60%.1-2 The classic triad of sudden hypoxia, hypotension
and coagulopathy with acute onset during labour or immediately after delivery
forms the hallmark of the AFES diagnosis, however AFES is primarily a clinical
diagnosis of exclusion. We present a case of successful maternal outcome
following severe amniotic fluid embolism after placental abruption and
intrauterine fetal demise.
PMID- 27607090
TI - Stroke Family/Whanau pilot project.
PMID- 27607091
TI - Riding in cars with boys, and girls, while smoking...in New Zealand.
PMID- 27607092
TI - A continuation of 10% annual tobacco tax increases until 2020: Modelling results
for smoking prevalence by sex and ethnicity.
PMID- 27607093
TI - Perspectives of New Zealand health professionals and smokers on e-cigarettes.
PMID- 27607094
TI - Does smoking cessation prior to elective spinal surgery lead to long-term smoking
abstinence.
PMID- 27607096
TI - Hepatocellular Carcinoma: The Gap Between Eastern and Western Clinical Practice.
PMID- 27607095
TI - Simulation for Operational Readiness in a New Freestanding Emergency Department:
Strategy and Tactics.
AB - STATEMENT: Simulation in multiple contexts over the course of a 10-week period
served as a core learning strategy to orient experienced clinicians before
opening a large new urban freestanding emergency department. To ensure technical
and procedural skills of all team members, who would provide care without on-site
recourse to specialty backup, we designed a comprehensive interprofessional
curriculum to verify and regularize a wide range of competencies and best
practices for all clinicians. Formulated under the rubric of systems integration,
simulation activities aimed to instill a shared culture of patient safety among
the entire cohort of 43 experienced emergency physicians, physician assistants,
nurses, and patient technicians, most newly hired to the health system, who had
never before worked together. Methods throughout the preoperational term included
predominantly hands-on skills review, high-fidelity simulation, and simulation
with standardized patients. We also used simulation during instruction in
disaster preparedness, sexual assault forensics, and community outreach. Our
program culminated with 2 days of in-situ simulation deployed in simultaneous and
overlapping timeframes to challenge system response capabilities, resilience, and
flexibility; this work revealed latent safety threats, lapses in communication,
issues of intake procedure and patient flow, and the persistence of inapt or
inapplicable mental models in responding to clinical emergencies.
PMID- 27607097
TI - Nationwide Evaluation of Patient Selection for Minimally Invasive Distal
Pancreatectomy Using American College of Surgeons' National Quality Improvement
Program.
AB - OBJECTIVE: To assess current nationwide case selection factors for minimally
invasive distal pancreatectomy (MIDP) and identify actual risk factors for
adverse outcomes compared with open distal pancreatectomy (ODP). BACKGROUND:
Patient selection criteria that predict outcomes after MIDP remain unknown. As a
result, widespread adoption of this surgical technique may have been delayed and
its potential benefits possibly under-exploited. METHODS: Retrospective cohort
study of elective ODP and MIDP performed at 106 centers in 2014, using the
pancreas-targeted American College of Surgeons' National Quality Improvement
Program (ACS-NSQIP) database. Exclusion criteria were neoadjuvant treatment or
pancreatitis as only diagnosis. Primary outcome includes a composite major
morbidity metric, reflecting adverse events including mortality and reoperation.
Multivariable modeling was used to detect current selection factors and to
identify actual risk factors of composite major morbidity. RESULTS: A total of
928 patients underwent ODP (n = 472) or MIDP (n = 456) using a laparoscopic or
robot-assisted approach, 24% for pancreatic ductal adenocarcinoma (PDAC). Current
selection factors for MIDP were benign disease (odds ratio: OR: 1.56, CI: 1.10
2.21) and body mass index (BMI) 30-40 (OR: 1.41, CI: 1.04-1.91). Current
selection factors for ODP were PDAC (OR: 0.45, CI: 0.31-0.64), benign tumor size
>5 centimeters (OR: 0.40, CI: 0.23-0.67), and multivisceral procedures (OR: 0.39,
CI: 0.26-0.59). Risk factors for composite major morbidity did not differ between
ODP and MIDP. A trend was observed between MIDP and a lower risk of composite
major morbidity compared with ODP (OR: 0.43, CI: 0.17-1.07). CONCLUSIONS: Current
selection factors for ODP or MIDP (benign disease, tumor size, and BMI) do not
mitigate the risk of major morbidity. We found no evidence that MIDP should be
avoided based on tumor etiology or size, BMI, or patient physical status.
PMID- 27607099
TI - Predicting the Risk of Postoperative Respiratory Failure in Elective Abdominal
and Vascular Operations Using the National Surgical Quality Improvement Program
(NSQIP) Participant Use Data File.
AB - OBJECTIVE: This study aims to develop a Respiratory Failure Risk Score (RFRS)
with good predictability for elective abdominal and vascular patients to be used
in the outpatient setting for risk stratification and to guide preoperative
pulmonary optimization. SUMMARY BACKGROUND DATA: Postoperative respiratory
failure (RF), defined as ventilator dependency for more than 48 hours or
unplanned reintubation within 30 days, is associated with increased mortality and
hospital costs. Many tools have been previously described for risk
stratification, but few target elective surgical candidates. METHODS: Our
training sample included patients undergoing inpatient, nonemergent general and
vascular procedures sampled for the American College of Surgeon National Surgical
Quality Improvement Program 2012 Participant Use File. Multivariable logistic
regression identified independent preoperative risk factors associated with RF,
used to derive a weighted RFRS. We then determined goodness-of-fit and optimal
cutoff values through receiver operator characteristic analysis and Youden
indices to evaluate internal and external validity with a retrospective
institutional validation sample (2013 and 2014). RESULTS: Multivariable analysis
of 151,700 patients from the National Surgical Quality Improvement Program
Participant Use File identified 12 variables independently associated with RF.
The RFRS showed good external prediction in the validation sample with a c
statistic of 0.73 (95% confidence interval, 0.68-0.79). With the highest Youden
index, 30 was determined to be the optimal cutoff value with a sensitivity 0.62
and specificity of 0.75. Additional cutoff values of 15 and 40 optimized
sensitivity (>0.80) and specificity (>0.80), respectively. CONCLUSIONS: In the
preoperative setting, the RFRS can effectively stratify patients into low (<15),
moderate low (15-29), moderate high (30-39), and high risk (>39) to assist in
patient counseling and guide application of perioperative pulmonary optimization
measures.
PMID- 27607098
TI - Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients
With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.
AB - OBJECTIVES: This study evaluated individual risks of malignancy and proposed a
nomogram for predicting malignancy of branch duct type intraductal papillary
mucinous neoplasms (BD-IPMNs) using the large database for IPMN. BACKGROUND:
Although consensus guidelines list several malignancy predicting factors in
patients with BD-IPMN, those variables have different predictability and
individual quantitative prediction of malignancy risk is limited. METHODS:
Clinicopathological factors predictive of malignancy were retrospectively
analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in
Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate
information were excluded. RESULTS: The study cohort consisted of 2258 patients.
Malignant IPMNs were defined as those with high grade dysplasia and associated
invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had
intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive
carcinoma. To construct and validate the nomogram, patients were randomly
allocated into training and validation sets, with fixed ratios of benign and
malignant lesions. Multiple logistic regression analysis resulted in five
variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being
selected to construct the nomogram. In the validation set, this nomogram showed
excellent discrimination power through a 1000 times bootstrapped calibration
test. CONCLUSION: A nomogram predicting malignancy in patients with BD-IPMN was
constructed using a logistic regression model. This nomogram may be useful in
identifying patients at risk of malignancy and for selecting optimal treatment
methods. The nomogram is freely available at
http://statgen.snu.ac.kr/software/nomogramIPMN.
PMID- 27607100
TI - Swallowing Dysfunction and Quality of Life in Adults With Surgically Corrected
Esophageal Atresia/Tracheoesophageal Fistula as Infants: Forty Years of Follow
up.
AB - OBJECTIVES: The aim of the study was to evaluate and study the full spectrum of
swallowing dysfunction and long-term disease-specific outcomes in adults with
surgically corrected esophageal atresia/tracheaesophageal fistula (EA/TEF).
BACKGROUND: Long-term outcomes for adults who underwent EA/TEF repair because
infants are lacking. METHODS: We developed a disease-specific swallowing
dysfunction questionnaire (SDQ) to assess swallowing dysfunction and quality of
life (QOL) of adult patients with surgically corrected EA/TEF. Patients were
surveyed with the newly developed SDQ and with a generic QOL tool (36-Item Short
Form Health Survey). RESULTS: Ninety-seven patients underwent EA/TEF repair at
our institution from 1950 to 1997. Forty-six (61%) patients completed the survey.
Median follow-up was 40 years (range 18-63). Results suggest that some degree of
swallowing dysfunction is common (82%), worse with hard consistencies (70%), and
is associated with frequently needing sips of liquids to facilitate swallowing
(75%). The presence of swallowing dysfunction was, however, often mild and did
not seem to affect patients' food choices, or their day-to-day activities. QOL
did not differ from that of the general population, regardless of the presence or
absence of swallowing dysfunction. The presence of gastroesophageal reflux
disease (26%), esophageal stricture (39%), or both (15%) does not account for all
situations of swallowing dysfunction, nor does it significantly impact QOL.
CONCLUSIONS: Swallowing dysfunction is common in adults who underwent EA/TEF
repair as infants; however, patients reported minimal effect on QOL or day-to-day
activities. The SDQ is a valid and reliable tool to measure the full spectrum of
swallowing dysfunction in the EA/TEF repair population.
PMID- 27607101
TI - Letter in Response to "No Cytokine is an Island: IL-6 Alone is Not Enough to
Predict the Morbidity After Major Abdominal Surgery".
PMID- 27607103
TI - CRP Predicts Safe Patient Discharge After Colorectal Surgery.
PMID- 27607102
TI - Hospital Quality and Medicare Expenditures for Bariatric Surgery in the United
States.
AB - OBJECTIVE: To examine the relationship between hospital outcomes and expenditures
in patients undergoing bariatric surgery in the United States. BACKGROUND: As one
of the most common surgical procedures in the United States, bariatric surgery is
a major focus of policy reforms aimed at reducing surgical costs. These policy
mechanisms have made it imperative to understand the potential cost savings of
quality-improvement initiatives. METHODS: We performed a retrospective review of
38,374 Medicare beneficiaries undergoing bariatric surgery between 2011 and 2013.
We ranked hospitals into quintiles by their risk and reliability-adjusted
postoperative serious complications. We then examined the relationship between
upper and lower outcome quintiles with risk-adjusted total episode payments.
Additionally, we stratified patients by their risk (low, medium, high) of
developing a complication to understand how this impacted payment. RESULTS: We
found a strong correlation between hospital complication rates and episode
payments. For example, hospitals in the lowest quintile of complication rates had
average total episode payments that were $1321 per patient less than hospitals in
the highest quintile ($11,112 vs $12,433; P < 0.005). Cost savings was more
prominent amongst high-risk patients where the difference of total episode
payments per patient between lowest and highest quintile hospitals was $2160
($12,960 vs $15,120; P < 0.005). In addition to total episode payment savings,
hospitals with the lowest complication rates also had decreased costs for index
hospitalization, readmissions, physician services, and postdischarge ancillary
care compared with hospitals with the highest complication rates. CONCLUSIONS:
Medicare payments for bariatric surgery are significantly lower at hospitals with
low complication rates. These findings suggest that efforts to improve bariatric
surgical quality may ultimately help reduce costs. Additionally, these cost
savings may be most prominent amongst the patients at the highest risk for
complications.
PMID- 27607104
TI - ALPPS in Setting Minimally Invasive Surgery for Hepatocellular Carcinoma.
PMID- 27607105
TI - Human Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck
Squamous Cell Carcinoma.
PMID- 27607107
TI - Benchmark investigation of diamondoid-functionalized electrodes for nanopore DNA
sequencing.
AB - Small diamond-like particles, diamondoids, have been shown to effectively
functionalize gold electrodes in order to sense DNA units passing between the
nanopore-embedded electrodes. In this work, we present a comparative study of
Au(111) electrodes functionalized with different derivatives of lower
diamondoids. Focus is put on the electronic and transport properties of such
electrodes for different DNA nucleotides placed within the electrode gap. The
functionalization promotes a specific binding to DNA leading to different
properties for the system, which provides a tool set to systematically improve
the signal-to-noise ratio of the electronic measurements across the electrodes.
Using quantum transport calculations, we compare the effectiveness of the
different functionalized electrodes in distinguishing the four DNA nucleotides.
Our results point to the most effective diamondoid functionalization of gold
electrodes in view of biosensing applications.
PMID- 27607106
TI - Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D
Culture.
AB - Stem cell-derived inner ear sensory epithelia are a promising source of tissues
for treating patients with hearing loss and dizziness. We recently demonstrated
how to generate inner ear sensory epithelia, designated as inner ear organoids,
from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we
improve the efficiency of this culture system by elucidating how Wnt signaling
activity can drive the induction of otic tissue. We found that a carefully timed
treatment with the potent Wnt agonist CHIR99021 promotes induction of otic
vesicles-a process that was previously self-organized by unknown mechanisms. The
resulting otic-like vesicles have a larger lumen size and contain a greater
number of Pax8/Pax2-positive otic progenitor cells than organoids derived without
the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner
ear organoids with hair cells whose morphological, biochemical and functional
properties are indistinguishable from those of vestibular hair cells in the
postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role
during inner ear organoid formation as it does during inner ear development in
the embryo.
PMID- 27607108
TI - Patient and caregiver view on seizure detection devices: A survey study.
AB - PURPOSE: Seizure detection devices (SDD) may reduce the potential for seizure
related injury, SUDEP or status epilepticus. We performed a survey of persons
with epilepsy (PWE) and caregivers to assess their perspectives regarding the
features and priorities that should be considered in the design of these devices.
METHODS: PWE/caregiver completed a survey which assessed the worry of undetected
seizures, the impact of this concern on diurnal functioning/sleep and the level
of interest in using SDD. Furthermore, questions regarding acceptable rates of
false positive (FP)/negative (FN) alarms, acceptable time to generate an alarm
and insurance coverage were asked. RESULTS: 92 surveys were completed.
Respondents expressed significant worry of undetected seizures. The impact of
this concern on sleep and diurnal functioning was moderate. There is significant
interest in using SDDs. Most would use SDD constantly. The acceptable FP-FN rate
should be <=25%. The time until caregivers are alerted should be <=1min.
Regarding affordability, the majority would not use SDD unless covered by
insurance and a few would use if not covered but affordable. CONCLUSIONS: The
concern of undetected seizures is high among PWE and caregivers. Most expressed a
high interest in using SDDs. Accuracy and affordability were key.
PMID- 27607109
TI - Connectosomes for Direct Molecular Delivery to the Cellular Cytoplasm.
AB - Transport of biomolecules, drugs, and other reagents across the cell's plasma
membrane barrier is an inefficient and poorly controlled process, despite its
fundamental importance to biotechnology, cell biology, and pharmaceutics. In
particular, insufficient membrane permeability frequently limits the accumulation
of drugs and reagents in the cytoplasm, undermining their efficacy. While
encapsulating drugs in particles increases uptake by cells, inefficient release
of drugs from these particles into the cytoplasm ultimately limits drug efficacy.
In contrast, gap junctions provide a direct route to the cytoplasm that bypasses
the plasma membrane. As transmembrane channels that physically connect the
cytoplasm of adjacent cells, gap junctions permit transport of a diverse range of
molecules, from ions and metabolites to siRNA, peptides, and chemotherapeutics.
To utilize gap junctions for molecular delivery we have developed Connectosomes,
cell-derived lipid vesicles that contain functional gap junction channels and
encapsulate molecular cargos. Here we show that these vesicles form gap junction
channels with cells, opening a direct and efficient route for the delivery of
molecular cargo to the cellular cytoplasm. Specifically, we demonstrate that
using gap junctions to deliver the chemotherapeutic doxorubicin reduces the
therapeutically effective dose of the drug by more than an order of magnitude.
Delivering drugs through gap junctions has the potential to boost the
effectiveness of existing drugs such as chemotherapeutics, while simultaneously
enabling the delivery of membrane-impermeable drugs and reagents.
PMID- 27607110
TI - The Effects of Molding Helmet Therapy on Spring-Mediated Cranial Vault Remodeling
for Sagittal Craniosynostosis.
AB - There is no clear consensus for the optimal treatment of sagittal
craniosynostosis; however, recent studies suggest that improved neurocognitive
outcomes may be obtained when surgical intervention imparts active cranial
expansion or remodeling and is performed before 6 months of age. The authors
consider spring-mediated cranioplasty (SMC) to optimally address these
imperatives, and this is an investigation of how helmet orthoses before or after
SMC affect aesthetic outcomes.The authors retrospectively evaluated patients
treated with SMC and adjunct helmeting for sagittal synostosis. Patients were
stratified into 4 cohorts based on helmet usage: preop, postop, both, and
neither. The cephalic index (CI) was used to assess head shape changes and
outcomes. Twenty-six patients met inclusion criteria: 6 (23%) had preop, 11 (42%)
had postop, 4 (15%) had preop and postop, and 5 (19%) had no helmeting. Average
age at surgery was 3.6 months. Overall, CI improved from a mean 69.8 to 77.9
during an average 7-month course of care. Mean preoperative change in CI showed
greater improvement with preop helmet (1.3) versus not (0.0), (P = 0.029),
despite similar initial CI in these cohorts (70.4 and 69.6 respectively, P =
0.69). Nonetheless, all patient cohorts regardless of helmeting status achieved
similar final CIs (range 76.4-80.4; P = 0.72).In summary, preoperative molding
helmet therapy leads to improved CI at the time of spring-mediated cranioplasty.
However, this benefit does not necessarily translate into overall improved CI
after surgery and in follow-up, calling into question the benefits of molding
helmet therapy in this setting.
PMID- 27607111
TI - Endoscope-Assisted Enucleation of Mandibular Odontogenic Keratocyst Tumors.
AB - The keratocyst odontogenic tumor (KCOT) represents a rare and benign but locally
aggressive developmental cystic lesion usually affecting the posterior aspect of
the mandible bone, the treatment of which has always been raising debate, since
Philipsen first described it as a distinct pathological entity in 1956.Recent
studies have proposed the use of endoscope-assisted surgical technique, due to
the possibility given by the endoscope of improving the effectiveness of the
treatment of these lesions thanks to a better visualization of operative field
and though a better understanding of the pathology. In this article, we would
like to present our experience with the endoscope-assisted treatment of KCOT of
the posterior region of the mandible.From April 2000 to April 2012, 32 patients
treated for KCOT were enrolled in our retrospective study: patients were divided
in 2 groups according to the type of treatment, that is, 18 were treated with
traditional enucleation surgery (TES), and 14 patients underwent endoscopic
assisted enucleation surgery (EES).Fischer exact test and Kaplan-Meier curves
were used to compare the outcomes between the 2 focusing on the recurrence and
complication rates. In the TES group, patients we found a higher recurrence rate
(39%) and higher postoperative complication rate at 5-year follow-up.Our data
suggested, though, that EES seems to be a feasible alternative for the treatment
of posterior mandibular KCOT. Further studies and larger series are needed to
confirm these results.
PMID- 27607112
TI - Long-Term Surgical and Speech Outcomes Following Palatoplasty in Patients With
Treacher-Collins Syndrome.
AB - BACKGROUND: Cleft palate is present in one-third of patients with Treacher
Collins syndrome. The authors present long-term speech and surgical outcomes of
palatoplasty in this challenging patient population. METHODS: A retrospective
review of all patients with Treacher-Collins syndrome and cleft palate was
conducted over a 35-year period at a single institution. Demographics, palatal,
mandibular, airway, and surgical outcomes were recorded. Speech outcomes were
assessed by the same craniofacial speech pathologist. RESULTS: Fifty-eight
patients with Treacher-Collins syndrome were identified: 43% (25) had a cleft
palate and 16% (9) underwent palatoplasty at our institution. Cleft palate types
included 1 Veau I, 5 Veau II, 1 Veau III, and 2 Veau IV. Mean age at the time of
palatoplasty was 2.0 years (range, 1.0-6.7 years). Three patients had fistulas
(33%) and underwent repairs. Pruzansky classifications included 1 type IIA, 6
type IIB, and 2 type III. Seven patients completed long-term speech evaluations.
Mean age at follow-up was 13.9 years (range 2.2-24.3 years). Six patients had
articulatory velopharyngeal dysfunction related to Treacher-Collins syndrome. Two
patients had structural velopharyngeal dysfunction and required further
palatal/pharyngeal surgery. CONCLUSIONS: Cleft palate repair in patients with
Treacher-Collins syndrome has a high incidence of velopharyngeal dysfunction.
However, the majority of patients are articulatory-based in whom further surgery
would not provide benefit. Patients with Treacher-Collins syndrome and cleft
palate require close evaluation by a speech pathologist as the incidence of
articulatory dysfunction is high.
PMID- 27607113
TI - An Unconventional Presentation of Branchio-Oculo-Facial Syndrome.
AB - Branchio-oculo-facial syndrome (BOFS) is a rare disorder characterized by
branchial or pharyngeal arch malformations, ocular findings, and craniofacial
anomalies. Activating mutations in the enhancer-binding protein 2 alpha, TFAP2A,
gene is responsible for the autosomal-dominant inheritance of BOFS. While
documented patients of BOFS report wide variability in phenotype expressivity,
patients typically demonstrate cervical or infra-auricular anomalies, diverse
ocular malformations including microphthalmia and coloboma, and highly
characteristic pseudo-cleft or palate defects. The authors present the case of an
infant with an unconventional presentation of BOFS to highlight key
distinguishing features of this disorder, and to emphasize the importance of a
multidisciplinary approach in the diagnosis and management of these patients.
PMID- 27607114
TI - Normative Velopharyngeal Data in Infants: Implications for Treatment of Cleft
Palate.
AB - Identifying normative data related to velopharyngeal muscles and structures may
have clinical significance for infants born with cleft palate, especially as they
relate to selection of surgical intervention and postsurgical outcomes. Previous
studies suggest that patients whose anatomy postsurgically is dissimilar to that
of their normative counterparts are at risk for hypernasal speech. However,
studies have not documented what constitutes "normal" anatomy for the clinically
relevant population-that is, the infant population. The purpose of this study is
to examine a magnetic resonance imaging database (n = 29) related to normative
velopharyngeal structures and provide a preliminary comparison to 2 selected
patients with repaired cleft palate. Twenty-nine healthy infants between 9 and 23
months of age (mean = 15.2 months) with normal craniofacial and velopharyngeal
anatomy were recruited to participate in this study. Normative data were compared
to 2 infants with repaired cleft palate between 13 and 15 months of age (mean =
14 months). Quantitative craniometric and velopharyngeal measures from the
sagittal and oblique coronal image planes were collected. Variables of interest
included: levator muscle, velar, and craniometric measures. Females demonstrated
significantly larger intravelar segments compared with males. White infants
demonstrated significantly larger levator muscles compared to non-white infants.
Infants with repaired cleft palate demonstrated increased overall levator muscle
length and levator extravelar length compared with infants with normal
velopharyngeal anatomy.Data from the present study provide a normative database
for future investigators to utilize as a comparative tool when evaluating infants
with normal and abnormal velopharyngeal anatomy.
PMID- 27607115
TI - Novel Three-Dimensional Understanding of Maxillary Cleft Distraction.
AB - OBJECTIVES: To set forth a universal standard methodology for quantifying
volumetric and linear changes in the craniofacial complex, utilizing three
dimensional data captured from a cleft-lip palate patient who underwent rigid
external device (RED) distraction. METHODS: Cone beam computed tomography images
of a 14-year-old patient were captured using a Kodak 9500 (Atlanta, GA) Cone Beam
system device and a stereophotogrammetric system (3dMDface(TM) Atlanta, GA). The
subject was a nonsyndromic unilateral cleft-lip palate patient who received RED
distraction as part of maxillary advancement in conjunction with orthodontic
treatment. Preop (T1) and postop (T2) images were superimposed using Invivo 5.2.3
(San Jose, CA) software. Volumetric rendering of the airway, bone, and soft
tissues, as well as linear measurements were analyzed. Each measurement was
captured 10 times to ensure reliability and reproducibility of methodology.
RESULTS: Data from T1 to T2 revealed mean differences as follows: airway total
volume +5250 mm, minimum cross-sectional area +67.84 mm; bone +1719 mm, soft
tissue +44,432 mm. Mean of linear measurements: Pronasale 1.98 mm, Subnasale 3.35
mm, Labial superius 10.79 mm, Labial inferius 4.13 mm, Right alare 5.71 mm, Right
cheilion 7.83 mm, Left alare 4.97 mm, Left cheilion 5.50 mm, Pogonion 3.01 mm, B
point 2.49 mm, U1-U1 9.77 mm, and L1-L1 0.00 mm. P values are <0.001 for each
analysis. CONCLUSIONS: This paper represents a novel and innovative way to look
at prepost RED distractions in a three-dimensional format. A universal standard
analysis of the craniofacial complex can be implemented using the techniques and
method outlined in this study.
PMID- 27607116
TI - New Technique for Mandibular Symphyseal Distraction by a Double-Level Anchorage
and Fixation System: Advantages and Results.
AB - INTRODUCTION: A surgical technique to widen the mandible is the mandibular
midline distraction: the most common indications for mandibular midline
distraction are severe mandibular anterior crowding, severe mandibular transverse
deficiency, uni- or bilateral crossbite, impacted anterior teeth with inadequate
space, and tipped teeth. Commonly used distraction devices can be divided into 2
systems: bone-borne distraction system appliance, dental-borne distraction
systems. Each system has peculiar advantages, disadvantages, and different
indications. To combine advantages of both systems we developed a new technique
adopting an immediate basal bone widening with fixation after osteotomy and a
dental borne rigid lingual system for distraction. AIM: The aim of this work is
to show a new technique for symphysis mandibular distraction based on a double
level anchorage and fixation system on clinical patients showing final results
and advantages. METHODS: Two patients affected by dento-alveolar and basal bone
maxillary and mandibular transversal collapse even in association with other
skeletal malocclusion were selected. Patients were clinically and
radiographically studied and analyzed at different times before and after
surgery. Dental and basal bone measurements were performed clinically and
radiographically. RESULTS: The results were optimal with perfect dental arches
alignment followed by closing of the open bites with multiple-segmented surgery
in a second surgical time. No misalignment of the 2 mandibular halves was noticed
during the distraction procedure. DISCUSSION: Dental-bone discrepancies
correction is mandatory before orthodontic treatment alignment. Transversal jaw
expansion can be achieved safely and stably by distraction of both maxillae for
the combination of osteogenesis and histogenesis with augmentation of both bone
and soft tissue. Bone-borne distraction will result in more stable results;
dental-borne devices will result in more simple and aesthetically rewarding
procedures. Hybrid techniques usually show mixed results depending on the
characteristics of the device. For this reason we developed a combination of both
the aforementioned systems which is not a hybrid system but the combination of an
immediate expansion of the symphysis and fixation by 1 miniplate with only 2
screws acting like hinges during distraction, combined with a lingual distraction
system at the alveolar bone level. CONCLUSIONS: Bone-borne distraction systems
result in more efficient basal bone mandibular widening with increased stability
for dental results. For dental-borne appliance the advantages consist in no
second surgery need for their removal, no transmucosal hardware emergence and
better aesthetic, especially when lingual devices were used. Our technique
combines advantages of both procedures.
PMID- 27607117
TI - Preventing Suture Extrusion and Recurrence in Mustarde and Furnas Otoplasties by
Using Laterally Based Postauricular Dermal Flap, Long-Term Results.
AB - BACKGROUND: Prominent ear deformity (PD) is an unacceptable condition of pinna
that affects 5% of the population and is associated with emotional stress,
behavioral disturbances, and social restrictions in relationships. Conchal
hypertrphy, inadequate formation of antihelical fold, earlobe placement ahead
than it should be, or various combinations of these changes are main
characteristics of PD. Many surgical techniques have been described for the
PD.The authors' aim was to present laterally based postauricular dermal flap
combination with cartilage-sparing methods and effectiveness of this technique in
suture extrusion prevention and reducing the rate of recurrence with long-term
results. METHODS: Forty-one patients had bilateral and 6 patients had unilateral
PD, a total of 47 patients with a mean age of 14.48 were operated by using this
combined procedure. A laterally based supraperichondrial dermal flap was prepared
from a deepithelized elliptical postauricular incision. Mustarde and Furnas
suture techniques were used solely for PD correction. The dissected laterally
based dermal flap was fixed to the mastoid bone with sutures in stretched
position after reshaping the auricular cartilage with sutures. RESULTS: The
average helix-mastoid distance was (mm) 16.28 +/- 2.36, concha-mastoid angle was
25.71 +/- 0.96 degrees on 12-month measurements. The helix-mastoid distance
showed an increase of 1 to 3 mm, in the concha-mastoid angle measurements of 1
degrees to 2 degrees . Statistically significant changes were observed between
the average preoperative, postoperative 1. month, postoperative 12. month helix
mastoid distances (mm), and month concha-mastoid angle ( degrees ) measurements
(P = 0.0001). CONCLUSIONS: The laterally based postauricular dermal flap
technique is an effective method to prevent suture extrusion and recurrence which
are the most important complications of otoplasty procedure and easy to apply.
PMID- 27607118
TI - Osteocutaneous Second-Toe Free Flap as Alternative Option for Repair of Anterior
Oronasal Fistula: Long-Term Results in Selected Patients.
AB - INTRODUCTION: Palatal fistulas anterior to the incisive foramen, generally seen
as a complication of cleft lip and cleft palate repair, can be extremely
difficult to repair. The requirements of the defect necessitate nasal lining,
oral lining, and bone for maxillary arch continuity. Local pedicled flap has
limited use in such patients with extensive scarring from previous surgeries. The
authors have recently described a technique involving osteocutaneous free-tissue
transfer of second toe for anterior oronasal fistulas. METHODS: The authors
describe their experience of patients with anterior oronasal fistula who
underwent osteocutaneous free-tissue transfer of second toe. Between 1991 and
2014, 3 patients with oronasal fistulas were operated utilizing bilaminar
osteocutaneous free tissue transfer. Described are the surgical decision making,
postoperative course, and surgical outcomes. RESULTS: The mean age of the
patients at the time of the procedure was 45.3 years with a mean follow-up of
12.6 years. All the patients had significant improvement of their regurgitation
and speech difficulty. One of the patients with very large fistula had recurrence
of the fistula which was repaired by local advancement of the original free flap.
CONCLUSIONS: Use of osteocutanous second-toe free flap can provide complete
coverage of the fistula with nasal and oral skin lining and provides an
alternative option for complicated anterior oronasal fistula.
PMID- 27607119
TI - Analysis of Lipoasiprated Following Centrifugation: Wet Versus Dry Harvesting
Technique.
AB - BACKGROUND: The success of lipotransfer strongly depends on the harvesting,
processing, and placement of the lipoaspirated samples. This study was designed
to assess the histomorphometric characteristics and viability of fat harvested
using different techniques (wet and dry) following centrifugation, as described
by Coleman. METHODS: The study enrolled 85 consecutive, nonrandomized, healthy
patients from March 2010 to December 2014 (45 males and 40 females). The mean age
was 40 years (range, 18-59 years), and the mean body mass index was 25.8 (range,
24-32). The authors performed a histological analysis (hematoxylin/eosin),
morphometry (ImageJ 1.33 free-share image analysis software), and a viability
assessment (Trypan Blue exclusion test; Sigma-Aldrich, Milan, Italy) of the
lipoaspirated samples. RESULTS: The hematoxylin and eosin-stained sections
exhibited similar features; in particular, clear-cut morphological signs of
adipocyte disruption, apoptosis, or necrosis were not detected in the examined
samples. Morphometry confirmed the visual findings, and the values of the mean
surface area of the adipocyte vacuoles were not significantly different.
Additionally, the adipocyte viability was not significantly different in the
analyzed fat tissue samples. CONCLUSIONS: The results from this study showed, for
the first time, that there is not a reduction in the viability of fat grafts
harvested with the dry or wet technique following centrifugation according to
Coleman technique. Both methods of fat harvesting collect viable cells, which are
not influenced by standard centrifugation. The fat grafts harvested and processed
by this technique could be used in clinical settings without increasing the
reabsorption rate. LEVEL OF EVIDENCE: V.
PMID- 27607120
TI - A Novel Single-Staged Technique for the Treatment of Soft Tissue in an Oblique
Facial Cleft.
AB - INTRODUCTION: Oblique facial clefts are extremely rare and cause significant
morbidity. Treatment of these clefts is complex and requires a fundamental
understanding of cleft classification and techniques used for treatment of
clefts. METHODS: We describe a novel single-staged technique to repair the
Tessier no. 4 soft tissue cleft and reconstruct the buccal sulcus and bilaminar
lower eyelid by preserving normally excised tissue combined with standard
procedures. We also present a case report demonstrating the technique in an
adolescent female. The procedure incorporates turnover flaps from soft tissue
preservation within the cleft, a Mustarde cheek advancement flap, an anatomical
subunit lip repair, a dorsal nasal Rieger flap for ala repositioning, and a
lateral nasal flag flap. RESULTS: The single-staged soft tissue repair eliminated
the Tessier no. 4 cleft while simultaneously reconstructing the bilaminar lower
eyelid and buccal lining. Our patient had no complications within the
perioperative period. CONCLUSIONS: This novel single-staged technique for the
treatment of the soft tissue Tessier no. 4 cleft not only repairs the cleft but
also reconstructs the buccal sulcus and bilaminar lower eyelid with turnover
flaps preserved from the normally discarded excess soft tissue within the cleft.
The novel repair allows for the creation of a deeper fornix to aid with placement
of an orbital prosthesis and is ideal for use in underserved or remote locations.
PMID- 27607121
TI - Arterio-Venous Malformations of the Nose: Combined Approach for a Successful
Strategy.
AB - BACKGROUND AND PURPOSE: The purpose of the present study is to evaluate the
vascular malformations of the head and neck. They are uncommon lesions, but some
areas have a significant potential for fatality, due to their massive bleeding.
The vascular anatomy of the nose carries a high recurrence rate, due to the
unique characteristic of the nose, especially if deep vascular connection is
present. METHODS: The present article describes 2 patients of nasal dorsum
arteriovenous malformations, both using a combined procedure: preoperative
selective embolization, en-bloc tumor resection, and reconstruction with a
forehead flap. Two female patients with arterio-venous malformations of the nose
were examined, subjected to excision procedure and forehead flap reconstruction.
Current treatment requires surgical resection of the nose and in conjunction with
adjunctive endovascular embolization; it reduces arterio-venous malformations
recurrence. RESULTS: The authors report an endovascular and surgical technique to
treat nasal arterio-venous malformations, which permits a complete resection and
a reconstruction with a forehead flap. There were no major complications such as
recurrent ulceration, infection, postoperative bleeding, or flap failure. All the
patients responded positively and satisfactory results were achieved in both
female patients. CONCLUSIONS: To reduce the recurrence of arterio-venous
malformations, the multidisciplinary therapy is mandatory. Recent advances in
microsurgery and interventional radiology have greatly improved prognosis for
patients with arterio-venous malformations. Therefore, a preoperative selective
embolization followed by surgical excision seems to be a good compromise for
arterio-venous malformations therapy. The forehead flap, for its characteristics,
represents the better choice for nasal reconstruction.
PMID- 27607122
TI - Morphological and Morphometric Analysis of Foramen Magnum: An Anatomical Aspect.
AB - OBJECTIVE: To investigate the detailed morphological and morphometric analysis of
foramen magnum (FM) in dry cranii. METHODS: One hundred fifty skulls of
unidentified sex were macroscopically examined and were photographed with Canon
400B (55 mm objective). According to tooth eruption of the skulls, they were
accepted as adults. None of the examined skulls showed signs of prior cranial
surgery, malformation, or trauma. The evaluated study parameters that were
recorded with Vernier caliper in millimeter were as follows: antero-posterior
diameter from Basion to Opisthion, transverse diameter (largest distance between
the lateral margins of the FM), and the shape of the FM (Fig. 1). The shape of
the FM was determined according to FM index that was calculated by dividing
antero-posterior diameter by transverse diameter. When FM index was found greater
than or equal to 1.2, the foramen was accepted to be oval in shape. Whereas the
FM index was found less than 1.2, the foramen was accepted to be round in shape
The area of the FM was calculated by using 2 different formulas as described
previously by Radinsky (/4 * pi * w * h) and Teixeira (pi * {(h + w)/4}2), and
"pi" was accepted as 3.14 in both formulas. RESULTS: The results of descriptive
statistics and areas of the FMs were presented in Table 1. The mean antero
posterior diameter and transverse diameter of anteroposterior diameter by
transverse diameters were found as 34.38 +/- 2.38 and 28.95 +/- 2.19,
respectively. The mean area of the FMs estimated by Teixeria formula was
determined significantly larger than the mean area of the FMs estimated by
Radinsky formula (P <0.001). According to estimated FM index of the 150 adult dry
skulls, 87 (58%) of skulls were described as being round in shape and 63 (42%) of
skulls were described as being oval in shape (Fig. 1). CONCLUSION: The surgeons
must comprehend regarding the detailed morphological and morphometric features of
FM to avoid vital complications during the surgical procedures.
PMID- 27607123
TI - Anatomical Studies of the Orbital Cavity Using Three-Dimensional Computed
Tomography.
AB - OBJECTIVE: This study was designed to analyze the morphometric characteristics of
the orbital cavity using three-dimensional computed tomography in Asians.
METHODS: Two hundred seventy-six orbits in 142 Asians (74 men and 68 women) were
examined and compared according to age, sex, and laterality (right and left).
RESULTS: Mean orbital morphometric values were as follows. Orbital cavity depth
was 49.60 mm from optic foramen to orbitale (inferior) and 41.32 mm from optic
foramen to lacrimal crest (medial). Anterior and posterior orbital medial wall
heights were 17.73 and 12.76 mm, respectively. Medial, middle, and lateral
orbital floor lengths were 39.08, 29.56, and 20.08 mm, respectively. Anterior and
posterior orbital floor width was 21.87 and 12.00 mm, respectively. For the
orbital inferior-medial angle, anterior, middle, and posterior value was 132.11
degrees , 126.24 degrees , and 136.88 degrees , respectively. Inferior orbital
cavity depth, anterior orbital medial wall height, and orbital floor length
tended to increase with aging, whereas orbital floor width tended to decrease
with aging. No significant differences were found in terms of laterality, and
values were greater in men than in women. CONCLUSIONS: This quantitative analysis
of orbital measurements will allow surgeons to plan operations more accurately
and will help predict outcomes.
PMID- 27607125
TI - Minimally Invasive Firearm Projectile Removal With the Use of Image Intensifiers.
PMID- 27607126
TI - Preoperative Use of Radiopaque Materials on Fractured Zygomatic Arch.
AB - Fractures of the zygoma are relatively frequent and their management has been
extensively described. Above all, isolated zygomatic arch fractures comprise
about 10% of all zygomatic fractures. Temporal approach is common surgical
method, Gillies approach, but it has the limitation of blinded surgical approach.
So, the mobile intraoperative fluoroscan is used famously for more suitable
reduction, but it needs an additional man to control the machine and increases
irradiation doses. The authors got the simple idea, but so helpful tool, and it
has been performed since 2012. The authors have gotten good surgical results, so
introduce this idea that favors the surgery on isolated zygomatic arch fracture.
PMID- 27607127
TI - Outcome of Management of Vascular Malformations of Lip.
AB - OBJECTIVES: To describe the characteristics and outcome of management of vascular
malformations of lip. PLACE AND DURATION OF STUDY: The Department of Plastic
Surgery and Burn Unit, King Edward Medical University, Mayo Hospital, Lahore,
from January 2009 to December 2013. METHODS: A prospective case series of 38
patients with vascular malformation of lip was performed. Demographic information
and clinical features were noted. Treatment employed, complications, functional,
and cosmetic outcome were recorded. Surgical debulking was performed as
definitive treatment in all patients and nonsurgical techniques were added as
adjuvant modalities in 18 patients. Sclerotherapy was performed for venous
malformations in 10 patients. LASER was performed in 8 patients with capillary or
combined malformations. Arterial malformations were managed surgically without
embolization. Postexcision defects were closed primarily in 36 patients with Abbe
flap in 1 and nasolabial flap in another patient for reconstruction. RESULTS: Of
38 patients included in the study 20 (53%) were males with mean (SD) age 18 (6)
years. Twenty-one percent were high and 79% low-flow malformations (29% venous,
16% capillary, and 34% combined). Lower lip was involved in 70% patients with 95%
having difficulty in eating and 87% abnormal speech. Referring diagnosis was
incorrect in 35% patients. Postsclerotherapy and postexcision pain scores were
mean (SD) 5 (1.26) and 4 (1) respectively. All patients had improvement in eating
and speech with restoration of normal muscle function in mean (SD) 5.63 (1.2)
weeks. Ninety-five percent patients were satisfied with their outlook. One
patient had recurrence at 1 year follow-up. CONCLUSION: Surgical debulking with
proper use of adjuvant procedure for vascular malformations of lip produces best
functional and aesthetic results with minimal complications.
PMID- 27607128
TI - Curative Treatment of Oronasal Fistulas With a Silicone Obturator.
AB - Oronasal fistulas can occur as a complication and sometimes they are refractory
to the adequate surgical interventions. Two patients of oronasal fistula were
presented. The first one developed as a complication of nasal septal surgery.
Following 2 failed operative closure, a custom-made silicone obturator resulted
unexpectedly as the cure for the problem in this patient. Experience gained from
this patient was utilized in the second presented patient by simply insertion of
a tailored silicone obturator after elevation of the nasal lining under local
anesthesia to the oronasal fistula transorally allowed closure without any formal
surgical intervention. Silicone obturator application may be employed for
curative treatment of the oronasal fistulas avoiding complex surgical treatments.
PMID- 27607129
TI - Trochlear Nerve Schwannoma With Repeated Intratumoral Hemorrhage.
AB - Trochlear nerve schwannoma is extremely rare, with only 35 pathologically
confirmed patients being reported in the literature. Here, the authors report a
patient of trochlear nerve schwannoma in the prepontine cistern manifesting as
facial pain and double vision and presenting the image characteristics of
repeated intratumoral hemorrhage, which has never been reported in the
literature. Total tumor along with a portion of the trochlear nerve was removed
by using a retrosigmoid approach. Facial pain disappeared after operation, and
the diplopia remained. Follow-up studies have shown no tumor recurrence for 2
years and the simultaneous alleviation of diplopia. Information regarding the
clinical presentation, radiological features and surgical outcomes of trochlear
nerve schwannoma are discussed and reviewed in the paper.
PMID- 27607130
TI - Oro-Nasal Communication.
AB - INTRODUCTION: Breach in the palatal vault leading to an abnormal communication
between oral and nasal cavity is known as oro-nasal communication. It is an
uncommon presentation in day-to-day clinical practice except in some patients of
cleft lip and palate.Etiology may be congenital or acquired. Alveolar and palatal
cleft defects are the most common etiological factor. The acquired causes may be
trauma, periapical pathology, infections, neoplasms, postsurgical complications,
and radio and chemo necrosis.Clinical features like nasal regurgitation of food,
defective speech, fetid odor, bad taste, and upper respiratory tract and ear
infection are associated with oro-nasal communication.Management depends upon the
size and site of defect, age of patient, and associated comorbidity. The
definitive management is always surgical. Two layered closure provides greater
support and stability and reduces the risk of failure. Palatal rotational flaps
are suitable for smaller defects. The other local flaps are buccal mucosal flap,
tongue flap, and facial artery myomucosal flap. Temporoparietal galeal flap,
turbinate flap, free radial forearm flap, and scapular flap have also been
successfully used for closure of oronasal communication. Newer procedures like
the use of bone morphogenic protein, acellular dermal matrices, human amniotic
membrane, and distraction osteogenesis have been tried successfully. The rate of
recurrence is high.Unsuccessful surgical attempts and larger defects associated
with compromised medical conditions are better managed nonsurgically with
obturator incorporating the missing teeth.
PMID- 27607131
TI - Metastatic Renal Cell Carcinoma to the Oral Cavity.
AB - Metastases to the oral cavity are extremely rare events, representing less than
1% of all malignant oral tumors. Renal cell carcinoma constitutes about 3% of
solid tumors in adults, and it is the most frequent kidney neoplasm, representing
about 90% of kidney malignancies. Due to the silent growth of this neoplasm, most
patients have no symptoms and the diagnosis is belated, usually after metastases.
The present study reports an additional patient of metastatic renal cell
carcinoma to the oral cavity regarding the clinical and pathologic features.
PMID- 27607132
TI - Solitary Supraclavicular Fossa Masses.
AB - OBJECTIVE: The aim of this study is to present the diagnostic spectrum of
solitary supraclavicular fossa (SCF) masses in a Turkish context. The demographic
data of the patients and the effectivity of the diagnostic tools are also
discussed to improve current diagnostic strategies. PATIENTS AND METHODS: The
charts of patients who underwent surgical intervention for solitary SCF mass of
an unknown etiology between January 2005 and January 2015 were reviewed. Patients
presenting evidences of synchronous cancers and patients with a history of
previous cancers were excluded. The data encompassing the demographics of the
patients, the discriminative specifications, the histopathological diagnosis of
the masses, and the diagnostic tools used in the workup period were noted. The
descriptive data are presented and statistical analyses were performed using the
Mann-Whitney test, Fisher exact test, and Chi-squared tests. RESULTS: In total,
44 male (76%) and 14 (24%) female patients were enrolled in the study. Thirty
five masses (60%) were located in the left SCF and 23 masses (40%) in the right.
The masses were categorized as neoplastic (n = 31, 53%), inflammatory (n = 18,
31%), and congenital (n = 9, 16%). The 44 (76%) masses in our series were lymph
nodes (LNs), and 25 (57%) of them were malign, whereas 19 (43%) were either
inflammatory or benign. Male sex (P = 0.027) and the size of the mass (P = 0.017)
were significantly related to malign LNs. The patients' ages and sides of the
masses were not significantly different between the malign and benign LN groups.
CONCLUSIONS: Lymph nodes constitute the majority of solitary SCF masses. Although
imaging techniques and fine needle aspirations are routinely applied, excisional
biopsies are necessary in most cases to reach an exact diagnosis and to plan a
definitive treatment regime in this presented series.
PMID- 27607134
TI - Virtual 3D-cholangioscopy: Correlation with direct peroral cholangioscopy in a
patient with papillary cholangiocarcinoma.
PMID- 27607133
TI - Notes from the Field: Splenomegaly of Unknown Etiology in Congolese Refugees
Applying for Resettlement to the United States - Uganda, 2015.
AB - Approximately 70,000-90,000 refugees are resettled to the United States each
year, and during the next 5 years, 50,000 Congolese refugees are expected to
arrive in the United States. The International Organization for Migration (IOM)
performs refugee medical examinations overseas for the U.S. Refugee Resettlement
Program. In 2014, IOM reported that a large number of U.S.-bound Congolese
refugees from Uganda had spleens that were enlarged on examination. During two
evaluations of refugee populations in western Uganda in March and July 2015,
refugees with splenomegaly on physical examination were offered additional
assessment and treatment, including abdominal ultrasonography and laboratory
testing. Among 987 persons screened, 145 (14.7%) had splenomegaly and received
further testing. Among the 145 patients with splenomegaly, 63.4% were aged 5-17
years (median = 14.8 years). There was some evidence of family clustering, with
33 (22.7%) of the 145 cases occurring in families.
PMID- 27607135
TI - Targeting H19 by lentivirus-mediated RNA interference increases A549 cell
migration and invasion.
AB - BACKGROUND: Lung cancer is one of the most common and a lethal malignancy in the
world and non-small cell lung cancer (NSCLC) is the most usual type. H19 long non
coding RNA (lncRNA) plays essential roles in tumor development. But its role in
tumor metastasis is still unclear. MATERIALS AND METHODS: MACC1 RNAi and
Lentivirus-mediated H19-specific shRNA was used to establish H19 stable knocking
down A549 cells. Transwell assays were performed to examine the effect of H19
knocking-down on A549 cells migration and invasion. The downstream signaling
proteins targeted by H19 were also examined by western blot. AG1478 and U0126
were used as the inhibitor of EGFR and ERK1/2, respectively. RESULTS: The
knockdown of H19 increased the migration and invasion of A549 cells, and
knockdown of metastasis-associated in colon cancer 1 (MACC1) decreased the
migration and invasion of A549 cells. Furthermore, MACC1 protein targeted by H19
was upregulated as well as the downstream signaling proteins including epidermal
growth factor receptor (EGFR), beta-catenin, extracellular-signal-regulated
kinase 1/2 (ERK1/2). Inhibited the expression of EGFR or ERK1/2 significantly
decreased the migration and invasion of tumor cells. CONCLUSION: Our findings
showed that H19 functions as a suppressor of NSCLC and plays an important role in
the migration and invasion of NSCLC. More importantly, H19 may regulate NSCLC
metastasis through modulating cellular signaling pathway proteins related to cell
proliferation and cell adhesion, including MACC1, EGFR, beta-catenin and ERK1/2.
These results put forward our understanding of the detailed mechanism of H19
lncRNA regulating the process of NSCLC metastasis.
PMID- 27607136
TI - Anticipated regret and health behavior: A meta-analysis.
AB - OBJECTIVE: Risk beliefs are central to most theories of health behavior, yet many
unanswered questions remain about an increasingly studied risk construct,
anticipated regret. The authors sought to better understand anticipated regret's
role in motivating health behaviors. METHOD: The authors systematically searched
electronic databases for studies of anticipated regret and behavioral intentions
or health behavior. They used random effects meta-analysis to synthesize effect
sizes from 81 studies (n = 45,618). RESULTS: Anticipated regret was associated
with both intentions (r+ = .50, p < .001) and health behavior (r+ = .29, p <
.001). Greater anticipated regret from engaging in a behavior (i.e., action
regret) predicted weaker intentions and behavior, whereas greater anticipated
regret from not engaging in a behavior (i.e., inaction regret) predicted stronger
intentions and behavior. Anticipated action regret had smaller associations with
behavioral intentions related to less severe and more distal hazards, but these
moderation findings were not present for inaction regret. Anticipated regret
generally was a stronger predictor of intentions and behavior than other
anticipated negative emotions and risk appraisals. CONCLUSIONS: Anticipated
inaction regret has a stronger and more stable association with health behavior
than previously thought. The field should give greater attention to understanding
how anticipated regret differs from similar constructs, its role in health
behavior theory, and its potential use in health behavior interventions.
(PsycINFO Database Record
PMID- 27607137
TI - Childhood self-control predicts smoking throughout life: Evidence from 21,000
cohort study participants.
AB - OBJECTIVE: Low self-control has been linked with smoking, yet it remains unclear
whether childhood self-control underlies the emergence of lifetime smoking
patterns. We examined the contribution of childhood self-control to early smoking
initiation and smoking across adulthood. METHODS: 21,132 participants were drawn
from 2 nationally representative cohort studies; the 1970 British Cohort Study
(BCS) and the 1958 National Child Development Study (NCDS). Child self-control
was teacher-rated at age 10 in the BCS and at ages 7 and 11 in the NCDS.
Participants reported their smoking status and number of cigarettes smoked per
day at 5 time-points in the BCS (ages 26-42) and 6 time-points in the NCDS (ages
23-55). Both studies controlled for socioeconomic background, cognitive ability,
psychological distress, gender, and parental smoking; the NCDS also controlled
for an extended set of background characteristics. RESULTS: Early self-control
made a substantial graded contribution to (not) smoking throughout life. In
adjusted regression models, a 1-SD increase in self-control predicted a 6.9
percentage point lower probability of smoking in the BCS, and this was replicated
in the NCDS (5.2 point reduced risk). Adolescent smoking explained over half of
the association between self-control and adult smoking. Childhood self-control
was positively related to smoking cessation and negatively related to smoking
initiation, relapse to smoking, and the number of cigarettes smoked in adulthood.
CONCLUSIONS: This study provides strong evidence that low childhood self-control
predicts an increased risk of smoking throughout adulthood and points to
adolescent smoking as a key pathway through which this may occur. (PsycINFO
Database Record
PMID- 27607138
TI - Validated guidelines for tumor delineation on magnetic resonance imaging for
laryngeal and hypopharyngeal cancer.
AB - BACKGROUND: Validation of magnetic resonance imaging (MRI) and development of
guidelines for the delineation of the gross tumor volume (GTV) is of utmost
importance to benefit from the visibility of anatomical details on MR images and
to achieve an accurate GTV delineation. In the ideal situation, the GTV
delineation corresponds to the histopathologically determined 'true tumor
volume'. Consequently, we developed guidelines for GTV delineation of laryngeal
and hypopharyngeal tumors on MRI and determined the accuracy of the resulting
delineation of the tumor outline on histopathology as gold standard. MATERIAL AND
METHODS: Twenty-seven patients with T3 or T4 laryngeal/hypopharyngeal cancer
underwent a MRI scan before laryngectomy. Hematoxylin and eosin sections were
obtained from surgical specimens and tumor was delineated by one pathologist. GTV
was delineated on MR images by three independent observers in two sessions. The
first session (del1) was performed according to clinical practice. In the second
session (del2) guidelines were used. The reconstructed specimen was registered to
the MR images for comparison of the delineated GTVs to the tumor on
histopathology. Volumes and overlap parameters were analyzed. A target margin
needed to assure tumor coverage was determined. RESULTS: The median GTVs (del1:
19.4 cm3, del2: 15.8 cm3) were larger than the tumor volume on pathology (10.5
cm3). Comparable target margins were needed for both delineation sessions to
assure tumor coverage. By adding these margins to the GTVs, the target volumes
for del1 (median: 81.3 cm3) were significantly larger than for del2 (median: 64.2
cm3) (p <= 0.0001) with similar tumor coverage. CONCLUSIONS: In clinical
radiotherapy practice, the delineated GTV on MRI is twice as large as the tumor
volume. Validated delineation guidelines lead to a significant decrease in the
overestimation of the tumor volume.
PMID- 27607139
TI - CTXphi: Exploring new alternatives in host factor-mediated filamentous phage
replications.
AB - For a long time Ff phages from Escherichia coli provided the majority of the
knowledge about the rolling circle replication mechanism of filamentous phages.
Host factors involved in coliphages replication have been fully identified. Based
on these studies, the function of Rep protein as the accessory helicase directly
implicated in filamentous phage replication was considered a paradigm. We
recently reported that the replication of some filamentous phages from Vibrio
cholerae, including the cholera toxin phage CTXphi, depended on the accessory
helicase UvrD instead of Rep. We also identified HU protein as one of the host
factors involved in CTXphi and VGJphi replication. The requirement of UvrD and HU
for rolling circle replication was previously reported in some family of plasmids
but had no precedent in filamentous phages. Here, we enrich the discussion of our
results and present new preliminary data highlighting remarkable divergence in
the lifestyle of filamentous phages.
PMID- 27607140
TI - Grete Kellenberger-Gujer: Molecular biology research pioneer.
AB - Grete Kellenberger-Gujer was a Swiss molecular biologist who pioneered
fundamental studies of bacteriophage in the mid-20(th) century at the University
of Geneva. Her life and career stories are reviewed here, focusing on her
fundamental contributions to our early understanding of phage biology via her
insightful analyses of phenomena such as the lysogenic state of a temperate phage
(lambda), genetic recombination, radiation's in vivo consequences, and DNA
restriction-modification; on her creative personality and interactions with
peers; and how her academic advancement was affected by gender, societal
conditions and cultural attitudes of the time. Her story is important
scientifically, putting into perspective features of the scientific community
from just before the molecular biology era started through its early years, and
also sociologically, in illustrating the numerous "glass ceilings" that,
especially then, often hampered the advancement of creative women.
PMID- 27607141
TI - The diverse genetic switch of enterobacterial and marine telomere phages.
AB - Temperate bacteriophages possess a genetic switch which regulates the lytic and
lysogenic cycle. The genomes of the enterobacterial telomere phages N15, PY54 and
phiKO2 harbor a primary immunity region (immB) comprising genes for the prophage
repressor, the lytic repressor and a putative antiterminator, similar to CI, Cro
and Q of lambda, respectively. Moreover, N15 and phiKO2 contain 3 related
operator (OR) sites between cI and cro, while only one site (OR3) has been
detected in PY54. Marine telomere phages possess a putative cI gene but not a cro
like gene. Instead, a gene is located at the position of cro, whose product shows
some similarity to the PY54 ORF42 product, the function of which is unknown. We
have determined the transcription start sites of the predicted repressor genes of
N15, PY54, phiKO2 and of the marine telomere phage VP58.5. The influence of the
genes on phage propagation was analyzed in E. coli, Y. enterocolitica and
V.parahaemolyticus. We show that the repressors and antiterminators of N15,
phiKO2 and PY54 exerted their predicted activities. However, while the proteins
of both N15 and phiKO2 affected lysis and lysogeny by N15, they did not affect
PY54 propagation. On the other hand, the respective PY54 proteins exclusively
influenced the propagation of this phage. The immB region of VP58.5 contains 2
genes that revealed prophage repressor activity, while a lytic repressor gene
could not be identified. The results indicate an unexpected diversity of the
growth regulation mechanisms in these temperate phages.
PMID- 27607142
TI - Seasonal dynamics in community structure, abundance, body size and sex ratio in
two species of Neotropical annual fishes.
AB - Seven ephemeral pools on the coastal plain of southern Brazil were found to be
inhabited by three annual and 22 non-annual fish species. Two common annual
species (Austrolebias minuano and Cynopoecilus fulgens) exhibited clear seasonal
dynamics, with the appearance of young fishes in the austral autumn (May to June)
and a decline in abundance over the seasonal cycle. The third annual species,
Austrolebias wolterstorffii, was rare. No seasonal dynamics were observed in non
annual fishes. The relative abundance of non-annual fishes compared with annual
fishes increased over the seasonal cycle, but they coexisted widely. The size
structure of annual fishes suggested the presence of a single age cohort in most
pools though a second age cohort was registered in one pool in August, coinciding
with a large flooding. Strong sexual dimorphism in body size was found in C.
fulgens throughout the seasonal cycle, while no sexual dimorphism in body size
was found in A. minuano. Female-biased sex ratios were recorded in both common
annual fish species in the last three sampling dates (in spring), but not during
the first two sampling dates (in winter). The natural lifespan of annual fishes
was <8 months. Annual fishes disappeared before habitat desiccation in half of
the pools, while non-annual fishes were still present.
PMID- 27607143
TI - Deciphering the Structural Evolution and Electronic Properties of Magnesium
Clusters: An Aromatic Homonuclear Metal Mg17 Cluster.
AB - The structures and electronic properties of low-energy neutral and anionic Mgn (n
= 3-20) clusters have been studied by utilizing a widely adopted CALYPSO
structure searching method coupled with density functional theory calculations. A
large number of low-energy isomers are optimized at the B3PW91 functional with
the 6-311+G(d) basis set. The optimized geometries clearly indicate that a
structural transition from hollow three-dimensional configurations to filled-cage
like structures occurs at n = 16 for both neutral and anionic clusters. Based on
the anionic ground state structures, photoelectron spectra are simulated using
time-dependent density functional theory (TD-DFT) and compared with experimental
results. The good agreement validates that the current ground state structures,
obtained from the symmetry-unconstrained searches, are true global minima. A
detailed chemical bonding analysis distinctly indicates that the Mg17 cluster is
the first neutral locally pi-aromatic homonuclear all-metal cluster, which
perfectly satisfies Huckel's well-known 4N + 2 rule.
PMID- 27607144
TI - Stigma, self-blame, and satisfaction with care among patients with lung cancer.
AB - OBJECTIVE: We sought to understand the experiences of patients with lung cancer
and to see if attitudes varied by demographic factors. METHODS: We administered a
63-question survey by phone or online among 174 patients with lung cancer. Factor
analysis was used to identify two groups of questions with a conceptual
relationship and high Cronbach's alphas, stigma and satisfaction with care. We
used a multivariable analysis to identify predictors of self-blame and the
factors of stigma and satisfaction with care. RESULTS: Patients were satisfied
with the quality of their care and treatment choices but did not feel that there
is enough public support for or research in lung cancer. Predictors of lower
satisfaction with care were never being a smoker, lack of college education, not
living in a rural location, refusing to report income, and not knowing/not being
sure of stage. Self-blame was modest; in multivariable analysis, predictors of
self-blame were believing that smoking was a cause of their lung cancer, younger
age, male sex, living in a suburban location, and not knowing/not being sure of
the stage of the cancer. Reported stigma was low and the only predictor for
stigma was being married. Despite low scores on their personal experience of
stigma, patients reported a high degree of stigmatization of lung cancer in
general. Smoking was a significant predictor of personal stigma. CONCLUSION:
Despite satisfaction with their treatment and care, lung cancer patients feel
that society stigmatizes them as a general population. Patients who smoke are
more likely to report that they have personally experienced stigma.
PMID- 27607145
TI - Preliminary Evaluation of a Laparoscopic Common Bile Duct Simulator for Pediatric
Surgical Education.
AB - PURPOSE: Laparoscopic common bile duct exploration (LCBDE) decreases overall
costs and length of stay in patients with choledocolithiasis. However,
utilization of LCBDE remains low. We sought to evaluate a previously developed
general surgery LCBDE simulator among a cohort of pediatric surgical trainees.
The study purpose was to evaluate the content validity of an LCBDE simulator to
support or refute its use in pediatric surgery education. MATERIALS AND METHODS:
After IRB exempt determination, 30 participants performed a transcystic LCBDE
using a previously developed simulator and evaluated the simulator using a self
reported 28-item instrument. The instrument consisted of two primary domains
(Quality and Ability to Perform) that were rated using twenty-five 4-point rating
scales and one 4-point global rating scale. Validity evidence relevant to test
content was evaluated using a many-facet Rasch model. Interitem consistency was
estimated using Cronbach's alpha. P < .05 was considered statistically
significant. RESULTS: The highest combined observed averages were for the Value
subdomain (OA = 3.79), whereas the lowest ratings were for the Physical/visual
attributes subdomain (OA = 3.19). The averaged global rating was 3.14, consistent
with this simulator can be considered for use in pediatric LCBDE training, but
could be improved slightly. Rasch indices were favorable and supported evidence
relevant to test content. Interitem consistency estimates were also favorable,
with alpha values of 0.94 and 0.56 for Qualities and Ability, respectively.
CONCLUSIONS: Overall, participants rated the LCBDE simulator highly valuable for
pediatric surgical education and felt that it could be used as an educational
tool with minor modifications.
PMID- 27607146
TI - Systems Perspective of Morbillivirus Replication.
AB - Systems biology refers to system-wide changes in biological components such as
RNA/DNA (genomics), protein (proteomics) and lipids (lipidomics). In this review,
we provide comprehensive information about morbillivirus replication. Besides
discussing the role of individual viral/host proteins in virus replication, we
also discuss how systems-level analyses could improve our understanding of
morbillivirus replication, host-pathogen interaction, immune response and disease
resistance. Finally, we discuss how viroinformatics is likely to provide
important insights for understanding genome-genome, genome-protein and protein
protein interactions.
PMID- 27607148
TI - Change in Accommodation and Ocular Aberrations in Keratoconus Patients Fitted
With Scleral Lenses.
AB - PURPOSE: To evaluate the accommodative response to different accommodative
stimulus and to determine the changes in ocular higher-order aberrations with
accommodation in keratoconus patients fitted with mini scleral lenses. MATERIAL
AND METHODS: The study included 15 keratoconus patients wearing mini scleral
lenses (Misa Scleral Lens-Microlens, Arnhem, the Netherlands) and 15 keratoconus
patients wearing rigid gas permeable lenses. Hartmannn Shack aberrometer (IRX-3;
Imagine Eyes, Orsay, France) was used for the evaluation of accommodation.
Accommodative responses to the accommodative stimulus ranging from 0.5 to 5.0
diopters (D) with intervals of 0.5 D were recorded. Spherical, coma, trefoil
aberration, and root mean square (RMS) of total higher-order aberrations (HOAs,
third to sixth orders) at baseline, at 2.5 D stimulus, and at 5 D stimulus were
also recorded. RESULTS: Although accommodative response to accommodative stimulus
of 0.5 to 2.5 D (with 0.5 D intervals) was similar in both groups, accommodative
response to accommodative stimulus of 3.0 to 5.0 D was significantly lower in
keratoconus group wearing mini scleral lenses. The coma, spherical, trefoil
aberrations, and the RMS of total HOAs at baseline, at 2.5 D stimulus, and at 5 D
stimulus were not significantly different between the groups. However, changes in
the coma and trefoil aberrations and RMS of total HOA with 2.5 D and 5.0 D
stimulus were significant only in the RGP group. CONCLUSIONS: Accommodative
response to increasing accommodative stimulus was found to be impaired in
keratoconus patients wearing mini scleral lenses.
PMID- 27607147
TI - Structural Characterization of Fibrils from Recombinant Human Islet Amyloid
Polypeptide by Solid-State NMR: The Central FGAILS Segment Is Part of the beta
Sheet Core.
AB - Amyloid deposits formed from islet amyloid polypeptide (IAPP) are a hallmark of
type 2 diabetes mellitus and are known to be cytotoxic to pancreatic beta-cells.
The molecular structure of the fibrillar form of IAPP is subject of intense
research, and to date, different models exist. We present results of solid-state
NMR experiments on fibrils of recombinantly expressed and uniformly 13C, 15N
labeled human IAPP in the non-amidated, free acid form. Complete sequential
resonance assignments and resulting constraints on secondary structure are shown.
A single set of chemical shifts is found for most residues, which is indicative
of a high degree of homogeneity. The core region comprises three to four beta
sheets. We find that the central 23-FGAILS-28 segment, which is of critical
importance for amyloid formation, is part of the core region and forms a beta
strand in our sample preparation. The eight N-terminal amino acid residues of
IAPP, forming a ring-like structure due to a disulfide bridge between residues C2
and C7, appear to be well defined but with an increased degree of flexibility.
This study supports the elucidation of the structural basis of IAPP amyloid
formation and highlights the extent of amyloid fibril polymorphism.
PMID- 27607149
TI - Descemet Membrane Endothelial Keratoplasty for Epithelial Downgrowth After Clear
Corneal Cataract Surgery.
AB - OBJECTIVES: To describe the first case of Descemet membrane endothelial
keratoplasty (DMEK) combined with argon laser photocoagulation and intracameral 5
fluorouracil (5-FU) injection in a patient with epithelial downgrowth after
cataract surgery. METHODS: Case report and review of the literature. RESULTS: A
77-year-old female underwent uneventful cataract surgery using a clear corneal
incision in her left eye. Six months after surgery, an epithelial cell sheet
began to cover the posterior cornea and then spread to the anterior chamber
structures, leading to anterior synechia and corectopia at 2 years. Argon laser
photocoagulation was used to remove epithelial downgrowth on the iris surface.
However, retrocorneal epithelial downgrowth gradually progressed, resulting in
bullous keratopathy. DMEK with intracameral 5-FU injection was performed to
remove epithelial tissue and replace the diseased endothelium with healthy
endothelium. One year after surgery, her vision improved to 20/50 and the
endothelial cell count was 1,643 cells/mm in her left eye. There were no further
complications or recurrence of epithelial downgrowth. CONCLUSIONS: DMEK with
preoperative argon laser and intraoperative 5-FU is a useful option for the
treatment of diffuse epithelial downgrowths.
PMID- 27607150
TI - Novel platens to measure the hardness of a pentagonal shaped tablet.
AB - Tablet hardness, a measure of the breaking force of a tablet, is based on
numerous factors. These include the shape of the tablet and the mode of the
application of force. For instance, when a pentagonal-shaped tablet was tested
with a traditional hardness tester with flat platens, there was a large variation
in hardness measurements. This was due to the propensity of vertices of the
tablet to crush, referred to as an "improper break". This article describes a
novel approach to measure the hardness of pentagonal-shaped tablets using
modified platens. The modified platens have more uniform loading than flat
platens. This is because they reduce loading on the vertex of the pentagon and
apply forces on tablet edges to generate reproducible tablet fracture. The
robustness of modified platens was assessed using a series of studies, which
included feasibility and Gauge Repeatability & Reproducibility (R&R) studies. A
key finding was that improper breaks, generated frequently with a traditional
hardness tester using flat platens, were eliminated. The Gauge R&R study revealed
that the tablets tested with novel platens generated consistent values in
hardness measurements, independent of batch, hardness level, and day of testing,
operator and tablet dosage strength.
PMID- 27607151
TI - Self-Powered, One-Stop, and Multifunctional Implantable Triboelectric Active
Sensor for Real-Time Biomedical Monitoring.
AB - Operation time of implantable electronic devices is largely constrained by the
lifetime of batteries, which have to be replaced periodically by surgical
procedures once exhausted, causing physical and mental suffering to patients and
increasing healthcare costs. Besides the efficient scavenging of the mechanical
energy of internal organs, this study proposes a self-powered, flexible, and one
stop implantable triboelectric active sensor (iTEAS) that can provide continuous
monitoring of multiple physiological and pathological signs. As demonstrated in
human-scale animals, the device can monitor heart rates, reaching an accuracy of
~99%. Cardiac arrhythmias such as atrial fibrillation and ventricular premature
contraction can be detected in real-time. Furthermore, a novel method of
monitoring respiratory rates and phases is established by analyzing variations of
the output peaks of the iTEAS. Blood pressure can be independently estimated and
the velocity of blood flow calculated with the aid of a separate arterial
pressure catheter. With the core-shell packaging strategy, monitoring
functionality remains excellent during 72 h after closure of the chest. The in
vivo biocompatibility of the device is examined after 2 weeks of implantation,
proving suitability for practical use. As a multifunctional biomedical monitor
that is exempt from needing an external power supply, the proposed iTEAS holds
great potential in the future of the healthcare industry.
PMID- 27607152
TI - The development of lighting countermeasures for sleep disruption and circadian
misalignment during spaceflight.
AB - PURPOSE OF REVIEW: The review addresses the development of a new solid-state
lighting system for the International Space Station (ISS) that is intended to
enhance the illumination of the working and living environment of astronauts and
to improve sleep, circadian entrainment, and daytime alertness. RECENT FINDINGS:
Spaceflight missions often expose astronauts and mission support ground crews to
atypical sleep-wake cycles and work schedules. A recent, extensive study
describes the sleep characteristics and use of sleep-promoting pharmaceuticals in
astronauts before, during, and after spaceflight. The acceptability, feasibility,
and efficacy of the new ISS solid-state lighting systems are currently being
tested in ground-based, analog studies. Installation of this lighting system on
the ISS is scheduled to begin later this year. In-flight testing of this lighting
system is planned to take place during ISS spaceflight expeditions. SUMMARY: If
the new ISS lighting system is capable of improving circadian entrainment and
sleep during spaceflight, it should enhance astronaut health, performance, well
being, and safety. Such an advance would open the door to future lighting
applications for humans living on Earth.
PMID- 27607153
TI - Oronasal mask may compromise the efficacy of continuous positive airway pressure
on OSA treatment: is there evidence for avoiding the oronasal route?
AB - PURPOSE OF REVIEW: Continuous positive airway pressure (CPAP) delivered by nasal
mask is the gold standard treatment for obstructive sleep apnea (OSA). However,
oral and oronasal masks are also available. We considered experimental evidence
and reviewed clinical trials that evaluated the impact of oral and oronasal mask
on OSA treatment. RECENT FINDINGS: One recent study in 18 OSA patients that slept
with a customized oronasal mask with two sealed compartments showed that the
change of CPAP flow from nasal to oronasal and oral caused upper airway
obstruction because of posterior displacement of the tongue demonstrated by
nasoendoscopy. Oral masks use a mouthpiece that may stabilize the jaw and the
tongue and have shown to be effective. However, oral masks are not widely used in
clinical practice. Four out of five observational studies and all five reviewed
randomized studies showed a worse performance of oronasal when compared with
nasal masks. Oronasal masks were associated with higher residual apnea-hypopnea
index, lower adherence, more leaks, and less satisfaction than nasal mask in the
majority of the studies. SUMMARY: Nasal CPAP must be the first choice to treat
OSA. Patients on oronasal mask should be carefully followed. VIDEO ABSTRACT.
PMID- 27607154
TI - Noninvasive monitoring of CO2 during polysomnography: a review of the recent
literature.
AB - PURPOSE OF REVIEW: Sleep-related breathing disorders are complex conditions that
require the integration of clinical and sleep laboratory findings to support a
diagnosis. Analysis of carbon dioxide (CO2) levels during sleep provides
important additional information to the clinician that is not obtained from other
polysomnographic indices, and that may have a direct impact on both diagnosis and
patient mortality. Although arterial blood gas (ABG) is considered the gold
standard for assessing PaCO2 levels, there are numerous drawbacks. Noninvasive
methods for PaCO2 estimation include end-tidal and transcutaneous monitoring,
which allow for continuous monitoring of trends. RECENT FINDINGS: Review of the
recent literature suggests that transcutaneous methods correlate strongly with
PaCO2 levels and can provide an accurate surrogate in replacement of ABGs. End
tidal methods provide breath to breath information that can be used to assess
hypoventilation; however, they have more variability, especially in patients with
increased dead space and small tidal volumes. To date, however, there are limited
studies investigating noninvasive CO2 monitoring during sleep. SUMMARY: Given the
benefits of CO2 monitoring and the importance of assessing for hypercapnia,
noninvasive continuous CO2 monitoring should be considered for all patients
undergoing polysomnography.
PMID- 27607155
TI - The reality of sexsomnia.
AB - PURPOSE OF REVIEW: The purpose of this review is to help further the
understanding of the clinical profile of patients with sexsomnia and to better
understand the spectrum of the clinical manifestations of sexsomnia. We will
review the literature from the past decade on the subject and then compare it
with our own clinical experience from patients who were retrospectively
identified with sexsomnia at a tertiary sleep clinic over a 6-year period. RECENT
FINDINGS: The prevalence of sexual behaviours in sleep remains unknown, but it
seems to involve predominantly younger male adults who also frequently exhibit
other non-rapid eye movement-related parasomnias. Medication-induced cases have
been reported and treatment approach of sexsomnia greatly varies.Of 41
individuals with sexsomnia from our centre with a mean age of 32 (37 men),
manifestations of sexsomnia were variable; sexual intercourse was most frequently
reported overall, but the majority of women carried out masturbation. Violence
and aggression were described on 11 occasions. All patients were amnesic of
events. 73% had a history of another parasomnia. SUMMARY: Sexsomnia is frequently
associated with concurrent sleep conditions or drugs initiation. It is a real
clinical disorder which should be properly diagnosed and managed.
PMID- 27607156
TI - Primary Left Tibial Epithelioid Hemangioendotheliomas With Multiple Metastases
Revealed by FDG PET/CT Imaging.
AB - Bone epithelioid angiosarcoma is an extremely rare osseous malignancy with an
aggressive and destructive biological behavior. We present FDG PET/CT findings of
a 59-year-old woman with left lower limb pain for 1 month. The images revealed
abnormal activity in both left fibula and left tibia. In addition, abnormal
activity in the sacrum and enlarged retroperitoneal lymph nodes was also noted.
Pathological examination demonstrated bone epithelioid angiosarcoma.
PMID- 27607157
TI - Breast Cancer Incidentally Detected by 18F-Choline PET/CT in a Patient With
Recurrent Prostate Carcinoma.
AB - A 79-year-old man underwent F-choline PET/CT for biochemical recurrence of
prostate cancer. PET/CT images showed an area of elevated radiopharmaceutical
uptake in a left pelvic node. In addition, a small focus of increased
radiolabeled choline accumulation was seen in a small nodule of the right breast,
which was later histologically characterized as an infiltrating ductal carcinoma.
In this patient, choline PET/CT was critical in localizing prostate cancer
recurrence and identifying a second unsuspected malignancy.
PMID- 27607158
TI - Incidental Finding of Cerebellar Medulloblastoma on 68Ga-DOTATATE PET/CT in a
Patient With Appendiceal Carcinoid.
AB - Ga-DOTATATE PET/CT is increasingly used to image somatostatin receptor expressing
tumors. Various intracranial tumors including medulloblastoma are known to
express somatostatin receptors. We present a case of incidental cerebellar
medulloblastoma on a staging Ga-DOTATATE PET/CT for appendiceal carcinoid.
PMID- 27607159
TI - Clinical Significance of Quantitative 123I-MIBG SPECT/CT Analysis of
Pheochromocytoma and Paraganglioma.
AB - PURPOSE: This retrospective study compared the diagnostic performances of
quantitative versus visual analyses of I-MIBG scintigraphy in patients with
suspected pheochromocytoma and paraganglioma (PPGL). MATERIALS AND METHODS: SPECT
images were obtained 6 and/or 24 h after MIBG injection from 68 patients with
clinically suspected PPGL, with attenuation correction by low-dose unenhanced CT.
Planar images were also obtained at each time point. SUVs of retroperitoneal
tumors, including PPGLs, and physiological uptake by normal organs were measured
using the SPECT images. The diagnostic performance of the quantitative assessment
in differentiating PPGLs from other lesions or normal adrenal glands was assessed
using receiver operating characteristic analysis. The planar scans and 6-h and 24
h SPECT/CT images were also assessed visually. RESULTS: PPGLs showed a
significantly higher SUVmax (mean +/- SD = 9.97 +/- 3.86) than other
retroperitoneal lesions (3.85 +/- 1.51) or normal adrenal glands (3.91 +/- 1.20).
At an optimal cut-off of 6.57, the sensitivity, specificity, and accuracy of the
quantitative assessment for 6-h SPECT/CT in differentiating PPGLs was 78.6%,
96.3%, and 92.6%, respectively; the area under the curve was 0.878. The
diagnostic performance did not significantly differ between the quantitative and
visual analyses, but the specificity of the former tended to be higher at 6 h
(96.3% vs. 90.7%) and at 24 h (91.2% vs. 82.4%). CONCLUSIONS: The specificity,
but not the sensitivity, of the quantitative approach was higher than that of
visual assessment in differentiating PPGLs from other retroperitoneal pathologies
and from physiological uptake in the normal adrenal gland.
PMID- 27607160
TI - 18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary
Hamartomas: Reply.
PMID- 27607162
TI - Successful Treatment of Hepatic Metastases of Hormone Refractory Prostate Cancer
Using Radioligand Therapy With 177Lu-PSMA-617.
AB - An 81-year-old castrate-resistant prostate cancer man with multiple lymph node,
bone, and hepatic metastases received four cycles of Lu-PSMA-617 treatments at
our department from May to December 2015. All of his liver metastases showed PSMA
expression in Ga-PSMA PET performed before the first cycle. Under this therapy,
all of the metastases showed significant regression in size and PSMA expression
over time.
PMID- 27607161
TI - Comparison of PET/MRI With PET/CT in the Evaluation of Disease Status in
Lymphoma.
AB - PURPOSE: The primary aim was to compare the diagnostic performance of PET/MRI
(performed with basic anatomical MRI sequences) in detecting sites of disease in
adult patients with lymphoma compared with the current standard of care, PET/CT.
Secondary aims were to assess the additional value of diffusion-weighted imaging
to PET/MRI in disease detection and to evaluate the relationship between the
standardized uptake value on PET/MR and the apparent diffusion coefficient on
diffusion-weighted imaging. METHODS: Sixty-eight studies in 66 consecutive
patients with histologically proven Hodgkin or non-Hodgkin lymphoma were
prospectively evaluated. Each patient had whole body PET/CT, followed by whole
body PET/MR. Two experienced readers independently evaluated the PET/MRI studies,
and two other experienced readers independently evaluated PET/CT. Site of
lymphoma involvement and SUVmax at all nodal sites more avid than background
liver were recorded. Readers provided stage (in baseline cases) and disease
status (remission vs active disease). The apparent diffusion coefficient mean
value corresponding to the most avid PET site of disease was recorded. RESULTS:
Ninety-five nodal and 8 extranodal sites were identified on both PET/CT and
PET/MRI. In addition, 3 nodal and 1 extranodal sites were identified on PET/MRI.
For positive lesion detection, reader agreement in PET/MR was perfect between the
2 readers and almost perfect between PET/CT and PET/MR (k > 0.978). Intermodality
agreement between PET/CT and PET/MRI was also near perfect to perfect for
staging/disease status k = (0.979-1.000). SUVmax from PET/CT and PET/MRI
correlated significantly (Spearman rho correlation coefficient, 0.842; P <
0.001). Diffusion-weighted imaging did not alter lesion detection or staging in
any case. A negative correlation was demonstrated between ADC mean and SUVmax
(Spearman rho correlation coefficient r, -0.642; P < 0.001). CONCLUSIONS: PET/MRI
is a reliable alternative to PET/CT in the evaluation of patients with lymphoma.
Diffusion-weighted imaging did not alter diagnostic accuracy. With comparable
accuracy in detection of disease sites and added benefit of radiation dose
reduction, PET/MRI has a potential to become part of routine lymphoma imaging.
PMID- 27607163
TI - Diagnosis of Primary Intestinal-Type Adenocarcinoma in the Nasal Cavity by 18F
FDG PET/CT.
AB - A soft-tissue lesion in the left nasal cavity was found on a 70-year-old man,
which was pathologically proved to be an intestinal-type adenocarcinoma (ITAC) by
biopsy. F-FDG PET/CT scan was performed to exclude the possibilities of
metastasis from the other primary adenocarcinomas, but the nasal tumor was found
to be the only lesion with F-FDG avidity. The primary ITAC in the nasal cavity
was diagnosed, and it was resected successfully.
PMID- 27607164
TI - Mental Stress-Induced Myocardial Ischemia Related to Generalized Anxiety Disorder
in a Patient With Acute Coronary Syndrome and Normal Coronary Arteries.
AB - Mental stress-induced myocardial ischemia (MSIMI) has been described in patients
with acute coronary syndrome (ACS). We reported the case of a patient admitted
with ACS and MSIMI related to generalized anxiety disorder (GAD). Myocardial
perfusion imaging (MPI) after exercise stress and computed tomography coronary
angiography showed normal results. In contrast, MPI with mental stress documented
MSIMI. He began to improve 7 days after starting escitalopram and remained
without angina at 1-year follow-up. These data suggest the applicability of
mental stress radionuclide imaging for the detection of MSIMI in patients with
ACS and GAD, even in normal coronary arteries.
PMID- 27607165
TI - Quality and Safety in Health Care, Part XVI: The VA Surgical Quality Improvement
Program.
AB - As the result of a congressional mandate, the Veterans Health Administration (VA)
undertook an initiative called the National VA Surgical Risk study. The purpose
of this study was to collect information on its surgical patients to determine
outcome data, adjusted for patient risk factors. In 1994, the VA started its
National Surgical Quality Improvement Program (VASQIP). These efforts were one of
the earliest well-done nationwide systems to study and improve outcomes in
surgery adjusted for patient risk. Between 1991 and 2006, the VA hospitals
observed a decrease of mortality of 47% and a decrease of morbidity of 43% of
their patients in the first 30 days after an operation.
PMID- 27607166
TI - A Unique Case of Erdheim-Chester Disease With Cervical and Lumbosacral Nerve
Involvement: FDG PET/CT Finding.
AB - Cervical and lumbosacral nerve roots and plexus involvement in Erdheim-Chester
disease (ECD) is rare. A 50-year-old man with progressive edema in bilateral
lower extremities, numbness, weakness, and muscle atrophy of upper limb for 2
years had been misdiagnosed of neuritis or cervical spondylosis until he
presented bone pain. In addition to bilateral symmetric involvement in long
bones, bilateral hypermetabolism in cervical and lumbosacral nerve roots was
found by FDG PET/CT scan. ECD was diagnosed by bone biopsy. This case reported
the rare peripheral neural involvement and highlighted the advantage of FDG
PET/CT scan in evaluating the multisystem involvement of ECD.
PMID- 27607167
TI - Extensive Metastases on 18F-FDG PET/CT in Primary Lymphoepithelioma-Like
Carcinoma of the Ovary.
AB - We describe extensive metastatic lesions of very rare lymphoepithelioma-like
carcinoma originating from the ovary assessed by F-FDG PET/CT. A 59-year-old
woman presented with abdominal distention. Pelvis MRI demonstrated a large right
ovarian malignant lesion with massive lymphadenopathy suggesting lymphoma.
Patient underwent surgical removal. The lymphoepithelioma-like carcinoma arising
from the ovary based on immunohistochemistry was pathologically confirmed.
Multiple metastases including peritoneum, omentum, and lymph nodes were
confirmed. F-FDG PET/CT for staging and evaluation of metastasis after operation
showed multiple lymph node metastases. F-FDG PET/CT revealed hepatic metastasis
in the dome region of the right liver besides multiple skeletal metastases.
PMID- 27607168
TI - Tumor Heterogeneity Detected by 68Ga DOTATOC and 18F-FDG PET/CTs in One Malignant
Insulinoma With Involvement of the Portal Splenic Confluence and Ovarian
Metastases.
AB - A 67-year-old woman was referred for staging of an insulinoma. CT has shown a
pancreatic tumor, a portal thrombus, and an ovarian mass presumed not to be
related with the insulinoma. These three lesions were highly positive on Ga
DOTATOC PET/CT, leading to the hypothesis of a malignant insulinoma with
neoplastic vein thrombus and ovarian metastasis, which was subsequently confirmed
histologically. Despite severe hypoglycemia preventing fasting, F-FDG PET/CT was
informative, showing significant uptake by the thrombus, which corresponded to
the most aggressive lesion (Ki67 of 3.5% for the primary pancreatic tumor and
19.6% for the thrombus).
PMID- 27607169
TI - 18F-FDG PET/CT Imaging of Cauda Equina Syndrome Secondary to Leptomeningeal
Metastatic Breast Cancer.
AB - Cauda equina syndrome (CES) is an uncommon entity that may be caused by a variety
of conditions. It refers to dysfunction of the ventral, dorsal, sacral, and
coccygeal nerve roots in the region of the filum terminale. We present a case of
a 32-year-old woman with a history of BRCA1-positive metastatic breast cancer who
complained of lower extremity muscle weakness increasing over a 2-week period and
decreased sensation of the lower extremities accompanied by severe constipation
and suspected urinary retention with overflow incontinence. The patient underwent
whole-body F-FDG PET/CT and MRI of the spine with and without gadolinium-based
contrast.
PMID- 27607170
TI - A Case of Nasal Merkel Cell Carcinoma Draining to a Buccinator Sentinel Lymph
Node.
AB - A 73-year-old man diagnosed with Merkel cell carcinoma of the left nasal ala was
referred for preoperative scintigraphic sentinel lymph node mapping. In three
separate foci around the lesion, 0.2 mCi of Tc-sulfur colloid was intradermally
administered. Planar images demonstrated accumulation of tracer midway between
the nose and left ear. SPECT/CT images localized radiotracer uptake to the left
buccinator/buccal space, consistent with a buccinator lymph node, which is an
inconsistent part of the facial lymphatic drainage. This case illustrates the
added value of SPECT/CT and 3D reconstruction in sentinel lymph node
localization, particularly in the head and neck.
PMID- 27607171
TI - High Uptake of FDG Along a Biliary Stent.
AB - A 66-year-old woman presented with abdominal discomfort. Contrast-enhanced CT
revealed a mass in the pancreas and multiple liver metastases. Pathological
examination confirmed the mass to be primary pancreatic cancer. Endoscopic
insertion of a biliary stent was performed to prevent common bile duct
obstruction. Subsequently, she received combination chemotherapy, which resulted
in a complete response. FDG-PET-CT after chemotherapy revealed a high uptake of
FDG along the outline of the biliary stent, with complete disappearance of both
the primary and metastatic tumors.
PMID- 27607172
TI - Hepatopulmonary Shunt Reduction With 177Lu-DOTATATE Therapy.
AB - A 72-year-old man was diagnosed with well-differentiated neuroendocrine tumor of
unknown primary with liver metastasis. All liver lesions were detectable only on
Ga-DOTATATE PET/CT and were negative on F-FDG PET/CT. Intrahepatic Y
radioembolization therapy was planned, but the hepatopulmonary shunt fraction was
found to be 31.6%. Because the hepatopulmonary shunt fraction greater than 20% is
an absolute contraindication to radioembolization, we decided to give him Lu
DOTATATE therapy. He received 4 courses of Lu-DOTATATE and showed regression in
posttherapy Ga-DOTATATE PET/CT imaging. The hepatopulmonary shunt fraction was
reduced to 8% after Lu-DOTATATE therapy.
PMID- 27607173
TI - 68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer.
AB - PURPOSE: The aim of our study is to assess the pharmacokinetics and
biodistribution of Ga-PSMA-11 in patients suffering from primary prostate cancer
(PC) by means of dynamic and whole-body PET/CT. MATERIALS AND METHODS: Twenty
four patients with primary, previously untreated PC were enrolled in the study.
All patients underwent dynamic PET/CT (dPET/CT) scanning of the pelvis and whole
body PET/CT studies with Ga-PSMA-11. The evaluation of dPET/CT studies was based
on qualitative evaluation, SUV calculation, and quantitative analysis based on
two-tissue compartment modeling and a noncompartmental approach leading to the
extraction of fractal dimension (FD). RESULTS: A total of 23/24 patients (95.8%)
were Ga-PSMA-11 positive. In 9/24 patients (37.5%), metastatic lesions were
detected. PC-associated lesions demonstrated the following mean values:
SUVaverage = 14.3, SUVmax = 23.4, K1 = 0.24 (1/min), k3 = 0.34 (1/min), influx =
0.15 (1/min), and FD = 1.27. The parameters SUVaverage, SUVmax, k3, influx, and
FD derived from PC-associated lesions were significantly higher than respective
values derived from reference prostate tissue. Time-activity curves derived from
PC-associated lesions revealed an increasing Ga-PSMA-11 accumulation during
dynamic PET acquisition. Correlation analysis revealed a moderate but significant
correlation between PSA levels and SUVaverage (r = 0.60) and SUVmax (r = 0.57),
and a weak but significant correlation between Gleason score and SUVaverage (r =
0.33) and SUVmax (r = 0.28). CONCLUSION: Ga-PSMA-11 PET/CT confirmed its capacity
in detecting primary PC with a detection rate of 95.8%. Dynamic PET/CT studies of
the pelvis revealed an increase in tracer uptake in PC-associated lesions during
the 60 minutes of dynamic PET acquisition, a finding with potential applications
in anti-PSMA approaches.
PMID- 27607174
TI - 68Ga-NODAGA-RGDyK PET/CT Imaging in Esophageal Cancer: First-in-Human Imaging.
AB - Ga-NODAGA-RGDyK(cyclic) and FDG PET/CT were performed in a 39-year-old man for
the work-up of a moderately differentiated carcinoma of the gastro-esophageal
junction within a clinical study protocol. Although FDG PET images showed
intense, diffuse hypermetabolic lesion activity, NODAGA-RGDyK illustrated the neo
angiogenesis process with tracer uptake clearly localized in non-FDG-avid
perilesional structures. Neo-angiogenesis is characterized by alphanubeta3
integrin expression at the lesion surface of newly formed vessels. This case
supports evidence that angiogenesis imaging might therefore be a crucial step in
early disease identification and localization, metastatization potential, and in
monitoring the efficacy of antiangiogenic therapies.
PMID- 27607175
TI - Recommendations and Technical Aspects of 16alpha-[18F]Fluoro-17beta-Estradiol PET
to Image the Estrogen Receptor In Vivo: The Groningen Experience.
AB - The estrogen derivative 16alpha-F-fluoro-17beta-estradiol (FES) is a PET tracer
that has been used in a variety of preclinical and clinical studies to detect
estrogen receptor (ER) expression, mainly in breast cancer, but also for other
oncological indications. As a result of the success of these studies and the
potential applications of the tracer, FES starts to be implemented in routine
clinical practice. However, the number of centers using this tracer is still
limited and many nuclear medicine physicians and medical oncologists are still
unaware of the possibilities FES PET imaging offers. The aim of this article is
therefore to give an overview of the main indications of FES PET in oncology and
to provide recommendations on correct use of this imaging technique. This
includes precautions that have to be taken for patient preparation, procedures
for the acquisition of the scans, the physiological distribution of the tracer,
factors that might influence tracer uptake and guidance for image analysis,
quantification of tracer uptake, and reporting of the scans.
PMID- 27607176
TI - 18F-FDG PET/CT Evaluation of Ceritinib Therapy in Metastatic ALK-Positive Non
small Cell Lung Cancer.
AB - Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancers (NSCLC)
account for 3% to 7% of all NSCLC and require a standard treatment by crizotinib.
However, crizotinib resistance is frequent within the first 12 months of
treatment. Ceritinib is a novel tyrosine kinase inhibitor of ALK recently
introduced in France for metastatic or locally advanced crizotinib-resistant ALK
NSCLC. We report the first use of ceritinib in our institution with a spectacular
tumoral response after only 3 months of treatment. This case demonstrates the
major role of F-FDG PET/CT for monitoring the effectiveness of this new
treatment.
PMID- 27607177
TI - 68Ga-PSMA Uptake in Hepatocellular Carcinoma.
AB - Ga-PSMA based integrated PET/MRI is emerging as a novel imaging technique for the
staging of prostate carcinoma. We report a case of a 77-year-old man with raised
prostate-specific antigen who presented to us for Glu-NH-CO-NH-Lys-(Ahx)-[Ga
(HBED-CC)] (Ga-PSMA) simultaneous PET/MRI scan for prostate cancer evaluation. A
PSMA avid hepatic lesion on the background of cirrhotic liver was noted apart
from PSMA avid lesion in the peripheral gland of the prostate. On
histopathological examination, the hepatic lesion turned out to be hepatocellular
carcinoma.
PMID- 27607178
TI - Diffuse Elevated Abdominal Activity on 99mTc-Labeled Red Blood Cell Imaging in a
Pediatric Patient With Klippel Trenaunay Syndrome.
AB - Klippel Trenaunay syndrome commonly manifests as lower limb hypertrophy where
vascular malformation occurs. However, up to 20% of patients with Klippel
Trenaunay syndrome can have gastrointestinal involvement. An 18-year-old man with
known Klippel Trenaunay syndrome in the left lower extremity underwent Tc-labeled
red blood cell imaging to determine the site of gastrointestinal bleeding. The
images did not reveal the site of active bleeding. However, diffuse non-moving
activity in the left abdomen and pelvis was noted, which corresponded to
hypertrophied colon and related blood vessels, consistent with intestinal
involvement of Klippel Trenaunay syndrome.
PMID- 27607179
TI - Re: 18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary
Hamartomas.
PMID- 27607180
TI - Unexpected Detection of Urinary Bladder Cancer on Dual Phase 18F-NaF PET/CT in a
Patient With Back Pain.
AB - A 72-year-old man underwent F-NaF PET/CT to evaluate causes of lower back pain.
The PET images revealed multiple foci of increased activity in several vertebral
bodies, which might account for the patient's symptoms. In addition, the CT image
revealed partially calcified soft tissue mass in the posterior wall of the
urinary bladder, which was photopenic relative to the radioactive urine on early
PET images but became intense on delayed PET images. The diagnosis of
transitional cell carcinoma was made pathologically after a transurethral
resection of the mass.
PMID- 27607182
TI - Idiopathic Granulomatous Mastitis: Cytologic and Histologic Study of 65 Egyptian
Patients.
AB - BACKGROUND: The etiology of idiopathic granulomatous mastitis (IGM) is unknown,
and it is commonly misdiagnosed clinically and/or radiologically as breast
cancer. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is
still a matter of debate. The aim of the current study is to assess the value of
FNAC in the diagnosis of IGM, and to search for the presence of bacteria in IGM
with cystic vacuoles, which was described recently by a few authors. MATERIALS
AND METHODS: Retrospective study of cytologic smears and histologic tissue
sections of 65 Egyptian IGM cases was done along with microbiologic testing. A
comparison of the frequency of IGM in Egypt to that of other populations was also
made. RESULTS: IGM has typical FNA features which can easily exclude malignancy.
Histologically, cystic vacuoles were encountered in 35 out of 65 cases (53.9%),
with only 6 (17.14%) of these cases showing Gram-positive bacilli (GPB). The
frequency of IGM in Egypt is comparable to those in other Middle Eastern
countries but much higher than in Western countries. CONCLUSION: IGM is a common
breast disease in Egypt. FNAC in IGM has a high diagnostic accuracy. This study
supports the few recent studies that have detected GPB in IGM with cystic
vacuoles. Thus, bacteriologic examination in such cases may affect the treatment
strategy.
PMID- 27607181
TI - Pilot Investigation of PTSD, Autonomic Reactivity, and Cardiovascular Health in
Physically Healthy Combat Veterans.
AB - Posttraumatic stress disorder (PTSD), and combat-related PTSD in particular, has
been associated with increased rates of cardiovascular disease, and
cardiovascular-related death. However, less research has examined possible
factors that may link PTSD to poorer cardiovascular health in combat veteran
populations. The current pilot study investigated whether psychological
symptomology and autonomic reactivity to emotional scripts would relate to poorer
cardiovascular health in combat veterans without a current diagnosis of
cardiovascular disease. Male veterans (N = 24), who served in combat since
Operation Iraqi Freedom, completed a semi-structured interview and self-report
measures to assess psychological symptomology. Autonomic reactivity, measured
using heart rate variability (HRV; low to high frequency ratio), was obtained
during script-driven imagery of emotional memories. Cardiovascular health was
assessed using flow-mediated dilation (FMD) of the brachial artery. Correlational
analyses and discriminant analysis were used to assess the relationship between
psychological symptoms (PTSD, depression, anger, as measured via self-report),
autonomic reactivity to emotional scripts (HRV), and FMD. Overall, veterans in
the current study showed poor cardiovascular health despite their relatively
young age and lack of behavioral risk factors, with 15/24 exhibiting impaired FMD
(FMD < 5%). Psychological symptomology was not associated with FMD; whereas
autonomic reactivity to emotional (compared to neutral) scripts was found to
relate to FMD. Autonomic reactivity to negative scripts correctly classified
76.5% of veterans as having impaired versus normative FMD. Results from this
pilot study highlight the importance of cardiovascular screening with combat
veterans despite psychological diagnosis. Results also support the need for
longitudinal research assessing the use of autonomic reactivity to emotionally
valenced stimuli as a potential risk factor for poorer cardiovascular health.
PMID- 27607183
TI - Inter-Rater Reliability of Neck Reflex Points in Women with Chronic Neck Pain.
AB - BACKGROUND: Neck reflex points (NRP) are tender soft tissue areas of the cervical
region that display reflectory changes in response to chronic inflammations of
correlated regions in the visceral cranium. Six bilateral areas, NRP C0, C1, C2,
C3, C4 and C7, are detectable by palpating the lateral neck. We investigated the
inter-rater reliability of NRP to assess their potential clinical relevance.
METHODS: 32 consecutive patients with chronic neck pain were examined for NRP
tenderness by an experienced physician and an inexperienced medical student in a
blinded design. A detailed description of the palpation technique is included in
this section. Absence of pain was defined as pain index (PI) = 0, slight
tenderness = 1, and marked pain = 2. Findings were evaluated either by pair-wise
Cohen's kappa (K) or by percentage of agreement (PA). RESULTS: Examiners
identified 40% and 41% of positive NRP, respectively (PI > 0, physician: 155,
student: 157) with a slight preference for the left side (1.2:1). The number of
patients identified with >6 positive NRP by the examiners was similar (13 vs. 12
patients). K values ranged from 0.52 to 0.95. The overall kappa was K = 0.80 for
the left and K = 0.74 for the right side. PA varied from 78.1% to 96.9% with
strongest agreement at NRP C0, NRP C2, and NRP C7. Inter-rater agreement was
independent of patients' age, gender, body mass index and examiner's experience.
CONCLUSION: The high reproducibility suggests the clinical relevance of NRP in
women.
PMID- 27607185
TI - Three oncoming editorials with some suggestions on statistical analysis for
authors and readers.
PMID- 27607184
TI - Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like
Receptor Stimulation in Peripheral Monocytes.
AB - Tryptophan degradation along the kynurenine pathway is of central importance for
the immune function. Toll-like receptors (TLRs), representing the first line of
immune defence against pathogens, are expressed in various cell types. The most
abundant expression is found on monocytes, macrophages and dendritic cells. The
aim of this study was to investigate whether stimulation with different TLR
ligands induces the kynurenine pathway in human peripheral monocytes. Cell
supernatants were analysed using a liquid chromatography/mass spectrometry to
measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan.
Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the
production of kynurenine, but only stimulation of TLR-3 increased levels of
further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR
5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study
provides novel evidence demonstrating that TLR activation induces a pattern of
downstream tryptophan degradation along the kynurenine pathway in monocytes. The
results of this study may implicate that TLRs can be used as new drug targets for
the regulation of aberrant tryptophan metabolism along this pathway, a potential
therapeutic strategy that may be of importance in several disorders.
PMID- 27607187
TI - Evaluation of the efficacy of solifenacin and darifenacin for prevention of
catheter-related bladder discomfort: a prospective, randomized, placebo
controlled, double-blind study.
AB - BACKGROUND: Urinary catheterization during surgical interventions causes
postoperative catheter-related bladder discomfort (CRBD). Antimuscarinic agents
are the mainstay of treatment for overactive bladder (OAB). As the symptoms of
CRBD mimic to OAB, so we designed this study to assess the efficacy of
solifenacin and darifenacin for prevention of CRBD. METHODS: Ninety patients of
either sex undergoing elective spine surgery and requiring urinary
catheterization were randomly assigned into three groups to receive oral
solifenacin 5 mg (Group S), darifenacin 7.5 mg (Group D) and placebo (Group C) 1
hour prior to induction of anesthesia. Anesthesia technique was identical in all
the groups. Catheter-related bladder discomfort (CRBD) was evaluated in 4-point
scale (1 = no discomfort, 2 = mild discomfort, 3 = moderate discomfort, 4 =
severe discomfort), on arrival (0 hour) and at 1, 2, and 6 hours postoperatively.
Patients were provided patient-controlled analgesia with fentanyl for
postoperative pain relief. RESULTS: There were no significant differences in
demographic profile and fentanyl requirements (P>0.05). The prevalence and
severity of CRBD were significantly less in the group D and group S compared with
the group C at all time intervals (P<0.05). CONCLUSIONS: Pretreatment with oral
solifenacin or darifenacin reduces catheter-related bladder discomfort with no
clinically relevant significant side effects.
PMID- 27607186
TI - Influence of supraglottic airway device placement on cerebral hemodynamics.
AB - BACKGROUND: Supraglottic airway devices (SGDs) are of current use in anesthesia
practice and in emergency conditions. It has been suggested that cerebral blood
flow (CBF) can decrease after SGD insertion or cuff inflation; however, it is
uncertain if this reduction is caused by the SGD or the anesthetic drugs utilized
for the anesthetic procedure. During minor surgery we separated CBF measurements
by an adequate time interval in order to measure the distinctive changes in
cerebral hemodynamics associated with anesthesia induction, SGD insertion and
cuff inflation. METHODS: Patients scheduled for minor surgery requiring general
anesthesia and SGD placement were included. Middle cerebral artery mean flow
velocity (FVm-mca) and the Pulsatility Index (PI) were measured through use of
trans-cranial Doppler (TCD) at baseline, after anesthesia induction, SGD
insertion and cuff inflation, once a steady cardio-circulatory state was reached
and end tidal CO2 (etCO2) was within normal range. RESULTS: A total of 21
patients were included. Following anesthesia induction, in concomitance to a
reduction in mean arterial pressure (MAP), there was a mean decrease in FVm-mca
by 16.60 cm/s, P<0.005 and a mean increase in PI by 0.24, P<0.0015. MAP, FVm-mca
and PI did not change significantly, neither after SGD placement (P>0.05), nor
after SGD cuffing (P>0.05). CONCLUSIONS: SGD insertion and cuff inflation did not
influence cerebral hemodynamics in anesthetized patients undergoing minor
surgery. At normal etCO2 range, the CBF reduction with transient increase in PI
was associated with anesthesia induction and not SGD insertion itself.
PMID- 27607188
TI - Development of Complex Models to Study Co- and Polymicrobial Infections and
Diseases.
PMID- 27607189
TI - Structures of Ionic Liquids Having Both Anionic and Cationic Octyl Tails:
Lamellar Vacuum Interface vs Sponge-Like Bulk Order.
AB - Numerous experimental and computational studies have shown that the structure of
ionic liquids is significantly influenced by confinement and by interactions with
interfaces. The nature of the interface can affect the immediate ordering of
cations and anions, changing important rheological characteristics relevant to
lubrication. Most studies suggest that such changes are local or short-ranged and
that bulk properties are reestablished on a length scale of a few nanometers. The
current study focuses on the 1-methyl-3-octylimidazolium octylsulfate ionic
liquid for which both the cation and anion have moderate length linear alkyl
tails. For this system, we find that the bulk phase is dominated by the very
common sponge-like morphology characteristic of many ionic liquids. However, at
the vacuum interface, a lamellar structure is observed that is not restricted to
the vicinity of the surface but instead extends across the full 9 nm slab of our
simulation. We suspect that in reality it could extend significantly beyond this.
PMID- 27607190
TI - Integrative analysis of miRNA and mRNA paired expression profiling of primary
fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular
functions.
AB - Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its
molecular pathology remains poorly understood, impeding the development of
effective treatments. Although it has been established that multiple cell types,
including fibroblasts, keratinocytes, macrophages, and endothelial cells, all
contribute to inhibition of healing, less is known regarding contributions of
individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs
and evaluated their cellular and molecular properties in comparison to
nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and
mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses
identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC >
2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and
differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR
34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially
regulated. The involvement of these microRNAs in wound healing was investigated
by testing the expression of their downstream targets as well as by quantifying
cellular behaviors in prospectively collected and generated cell lines from 15
patients (seven DFUF and eight NFF samples). We found large number of downstream
targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA
profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on
paired miRNA-mRNA profiles predicted inhibition of cell movement and cell
proliferation, as well as activation of cell differentiation and senescence in
DFU fibroblasts, which was confirmed by cellular assays. We concluded that
induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an
important role in impairing multiple cellular functions, thus contributing to
overall inhibition of healing in DFUs.
PMID- 27607191
TI - Induction of Pulmonary Granuloma Formation by Propionibacterium acnes Is
Regulated by MyD88 and Nox2.
AB - Sarcoidosis is characterized by noncaseating granulomas with an unknown cause
that present primarily in the lung. Propionibacterium acnes, an immunogenic
commensal skin bacterium involved in acne vulgaris, has been implicated as a
possible causative agent of sarcoidosis. Here, we demonstrate that a viable
strain of P. acnes isolated from a patient with sarcoidosis and instilled
intratracheally into wild-type mice can generate pulmonary granulomas similar to
those observed in patients with sarcoidosis. The formation of these granulomas is
dependent on the administration of viable P. acnes. We also found that mice
deficient in the innate immunity adapter protein MyD88 had a greater number and a
larger area of granuloma lesions compared with wild-type mice administered P.
acnes. Early after P. acnes administration, wild-type mice produced
proinflammatory mediators and recruited neutrophils into the lung, a response
that is dependent on MyD88. In addition, there was an increase in granuloma
number and size after instillation with P. acnes in mice deficient in CybB, a
critical component of nicotinamide adenine dinucleotide phosphate oxidase
required for the production of reactive oxygen species in the phagosome. Myd88-/-
or Cybb-/- mice both had increased persistence of P. acnes in the lung, together
with enhanced granuloma formation. In conclusion, we have generated a mouse model
of early granuloma formation induced by a clinically relevant strain of P. acnes
isolated from a patient with sarcoidosis, and, using this model, we have shown
that a deficiency in MyD88 or CybB is associated with impaired bacterial
clearance and increased granuloma formation in the lung.
PMID- 27607194
TI - Synthesis and Deprotonation of Aminophosphane Complexes: First K/N(H)R
Phosphinidenoid Complexes and Access to a Complex with a P2 N-Ring Ligand.
AB - Synthesis of 1,1'-bifunctional aminophosphane complexes 3 a-e was achieved by the
reaction of Li/Cl phosphinidenoid complex 2 with various primary amines (R=Me,
iPr, tBu, Cy, Ph). Deprotonation of complex 3 a (R=Me) with potassium
hexamethyldisilazide yielded a mixture of K/NHMe phosphinidenoid complex 4 a and
potassium phosphanylamido complex 4 a'. Treatment of complex 3 c (R=tBu) and e
(R=Ph) with KHMDS afforded the first examples of K/NHR phosphinidenoid complexes
4 c and e. The reaction of complex 3 c with 2 molar equivalents of KHMDS followed
by PhPCl2 afforded complexes 5 c,c', which possess a P2 N-ring ligand. All
complexes were characterized by NMR, IR, MS, and microanalysis, and additionally,
complexes 3 b-e and 5 c' were scrutinized by single-crystal X-ray
crystallography.
PMID- 27607193
TI - The consequences of using advanced physical assessment skills in medical and
surgical nursing: A hermeneutic pragmatic study.
AB - AIMS AND OBJECTIVES: The aim of this study was to explore the consequences of the
nurse's use of advanced assessment skills on medical and surgical wards.
BACKGROUND: Appropriate, accurate, and timely assessment by nurses is the
cornerstone of maintaining patient safety in hospitals. The inclusion of
"advanced" physical assessment skills such as auscultation, palpation, and
percussion is thought to better prepare nurses for complex patient presentations
within a wide range of clinical situations. DESIGN: This qualitative study used a
hermeneutic pragmatic approach. METHOD: Unstructured interviews were conducted
with five experienced medical and surgical nurses to obtain 13 detailed
narratives of assessment practice. Narratives were analyzed using Van Manen's six
step approach to identify the consequences of the nurse's use of advanced
assessment skills. RESULTS: The consequences of using advanced assessment skills
include looking for more, challenging interpretations, and perseverance. The use
of advanced assessment skills directs what the nurse looks for, what she sees,
interpretation of the findings, and her response. It is the interpretation of
what is seen, heard, or felt within the full context of the patient situation,
which is the advanced skill. CONCLUSION: Advanced assessment skill is the means
to an accurate interpretation of the clinical situation and contributes to
appropriate diagnosis and medical management in complex patient situations.
RELEVANCE TO CLINICAL PRACTICE: The nurse's use of advanced assessment skills
enables her to contribute to diagnostic reasoning within the acute medical and
surgical setting.
PMID- 27607192
TI - StrongNet: An International Network to Improve Diagnostics and Access to
Treatment for Strongyloidiasis Control.
PMID- 27607195
TI - Hybrid Sol-Gel-Derived Films That Spontaneously Form Complex Surface
Topographies.
AB - Surface patterns over multiple length scales are known to influence various
biological processes. Here we report the synthesis and characterization of new,
two-component xerogel thin films derived from carboxyethylsilanetriol (COE) and
tetraethoxysilane (TEOS). Atomic force microscopy (AFM) reveals films surface
with branched and hyper branched architectures that are ~2 to 30 MUm in diameter,
that extend ~3 to 1300 nm above the film base plane with surface densities that
range from 2 to 77% surface area coverage. Colocalized AFM and Raman spectroscopy
show that these branched structures are COE-rich domains, which are slightly
stiffer (as shown from phase AFM imaging) and exhibit lower capacitive force in
comparison with film base plane. Raman mapping reveals there are also discrete
domains (<=300 nm in diameter) that are rich in COE dimers and densified TEOS,
which do not appear to correspond with any surface structure seen by AFM.
PMID- 27607196
TI - Clinical, radiographic and functional efficacy of abatacept in routine care for
rheumatoid arthritis patients: Abatacept Leading Trial for RA on Imaging
Remission (ALTAIR) study.
AB - OBJECTIVES: To investigate the efficacy and safety of abatacept for treating
patients with rheumatoid arthritis (RA) in routine clinical practice and to
determine the prognostic factors affecting clinical outcomes. METHODS: We
performed a retrospective study of 194 RA patients treated with abatacept.
Clinical outcomes at 1 year after the treatment were assessed. Joint damage was
assessed by the van der Heijde-modified total Sharp score (mTSS). RESULTS: Of the
194 patients, abatacept was discontinued in 51 patients, resulting in a retention
rate at week 52 of 73.7%. At week 52, 23.7% of patients achieved clinical
remission (SDAI <=3.3). Lower SDAI and higher RF titre at baseline were the
prognostic factor for SDAI at 52 weeks. Structural remission (DeltamTSS <=0.5)
was achieved in 73.4% of patients. However, clinical relevant radiographic
progression which was defined as an increase in DeltamTSS >3 in a year, occurred
in 7.6% of patients. Likewise, rapid radiological progression, which was defined
as an increase in DeltamTSS >5 in a year, was observed in 6.4% of patients. 16.5%
of patients achieved comprehensive disease remission, which was defined as SDAI
<=3.3, HAQ-DI <=0.5, DeltamTSS <=0.5, while 22.4% of patients achieved
comprehensive disease control (CDC), which was defined as SDAI <=11.0, HAQ-DI
<=0.5, DeltamTSS <=0.5. CONCLUSIONS: The present results confirm that abatacept
is effective and safe in routine clinical practice. It is possible that abatacept
is more effective in seropositive RA patients with significant immunological
abnormality.
PMID- 27607197
TI - Onset-to-device time of patients who arrive at off-hours: Importance of
prehospital management and public awareness for patients with ST-segment
elevation myocardial infarction.
AB - AIM: The influence of the time of arrival at the hospital on the door-to-device
(DTD) time has been investigated; however, the influence on the onset-to-device
(OTD) time is unclear in ST-segment elevation myocardial infarction (STEMI)
patients. The aim of this study was to investigate the relationship between the
time of arrival at the hospital and the OTD time in STEMI patients. METHODS: We
evaluated 377 STEMI patients who underwent primary percutaneous coronary
intervention (pPCI) between January 2008 and December 2014. RESULTS: During the
study period, 222 patients arrived at our hospital between 9 AM and 9 PM (on
hours group) and 155 patients arrived between 9 PM and 9 AM (off-hours group).
The DTD time was longer in the off-hours group than in the on-hours group (50.4
vs 39.3 minutes; P<.001), while the OTD time was longer in the on-hours group
than in the off-hours group (285.7 vs 184.5 minutes, P<.001). The 30-day
mortality and peak creatinine kinase levels were similar between the groups.
Transfer from a non-pPCI-capable facility to our hospital was more common in the
on-hours group than in the off-hours group (49.1% vs 15.5%, P<.001). The OTD time
was shorter in patients who directly visited our hospital than in those who were
transferred (172.9 vs 338.5 minutes, P<.001). CONCLUSIONS: The OTD time might be
markedly longer in STEMI patients who arrive at the hospital during on-hours than
in those who arrive at the hospital during off-hours because of the underuse of
emergency medical services at STEMI onset.
PMID- 27607229
TI - The development of inhibitory saccadic trajectory deviations correlates with
measures of antisaccadic inhibition.
AB - Chronological age is related positively to a participant's ability to inhibit
distracting information. Inhibition can be measured using the trajectory
deviation of a saccade. Saccadic curvature away from distracting visual
information is controlled through top-down inhibition mediated by the frontal eye
fields. In the present study, we aimed to further test the saccadic trajectory
deviation paradigm's sensitivity to the development of frontal inhibitory
procuresses by comparing its measure of saccadic inhibition with that of a widely
used paradigm, namely, the antisaccade task. We show that the later 'inhibition'
phase of the trajectory deviation function correlated strongly with the measure
of antisaccadic inhibition obtained in the same individuals. As expected, the
earlier 'capture' phase of the trajectory deviation function, which does not
represent the involvement of frontal structures, did not correlate with
antisaccadic inhibition. Further, both measures of frontal inhibition increased
with chronological age.
PMID- 27607228
TI - Chirality Relay in 2,2'-Substituted 1,1'-Binaphthyl: Access to Propeller
Chirality of the Tricoordinate Boron Center.
AB - It is a challenging issue to achieve propeller chirality for triarylboranes owing
to the low transition barrier between the P and M forms of the boron center.
Herein, we report a new strategy to achieve propeller chirality of
triarylboranes. It was found that the chirality relay from axially chiral 1,1'
binaphthyl to propeller chirality of the trivalent boron center can be realized
when a Me2 N and a Mes2 B group (Mes=mesityl) are introduced at the 2,2'
positions of the 1,1'-binaphthyl skeleton (BN-BNaph) owing to the strong pi-pi
interaction between the Me2 N-bonded naphthyl ring and the phenyl ring of one
adjacent Mes group, which not only exerts great steric hindrance on the rotation
of the two Mes groups but also gives unequal stability to the two configurations
of the boron center for a given configuration of the binaphthyl moiety. The
stereostructures of the boron center were fully characterized through 1 H NMR
spectroscopy, X-ray crystal analyses, and theoretical calculations. Detailed
comparisons with the analog BN-Ph-BNaph, in which the Mes2 B group is separated
from 1,1'-binaphthyl by a para-phenylene spacer, confirmed the essential role of
pi-pi interaction for the successful chirality relay in BN-BNaph.
PMID- 27607230
TI - Effect of hindlimb unloading on stereological parameters of the motor cortex and
hippocampus in male rats.
AB - Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its
cellular and molecular mechanisms are not well understood. The aim of the present
study was to determine the stereological parameters of the brain areas involved
in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU
condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were
divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of
motor cortex and hippocampus, the numerical cell density of neurons in layers I,
II-III, V, and VI of the motor cortex, the entire motor cortex as well as the
primary motor cortex, and the numerical density of the CA1, CA3, and dentate
gyrus subregions of the hippocampus were estimated. No significant differences
were observed in the evaluated parameters. Our results thus indicated that motor
cortical and hippocampal atrophy and cell loss may not necessarily be involved in
the motion and spatial learning memory impairment in the rat.
PMID- 27607231
TI - Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory
Failure with Mycophenolic Acid.
AB - Organising pneumonia (OP) is usually promptly responsive to corticosteroid
treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven
fibrosing OP causing respiratory failure. All cases presented with peribronchial
and subpleural consolidations, had a fibro-inflammatory infiltrative component in
the alveolar septa, and only had a partial and unsatisfactory response to
corticosteroids. However, they responded to mycophenolic acid (MPA) treatment
with resolution of respiratory failure as well as clinical and functional
improvement. MPA as an additional treatment option for aggressive forms of
fibrosing OP and interstitial lung disease needs to be further explored.
PMID- 27607232
TI - Impact of sesquiterpenes from Inula racemosa (Asteraceae) on growth, development
and nutrition of Spodoptera litura (Lepidoptera: Noctuidae).
AB - BACKGROUND: The use of botanical pesticides for protecting crops from insect
pests has assumed greater importance all over the world owing to growing
awareness of harmful effects of indiscriminate use of synthetic pesticides. Inula
racemosa Hook. f. (Asteraceae), a medicinally important perennial herb, is rich
in sesquiterpenes with many biological activities. The present studies were
conducted with the objective to evaluate the sesquiterpenes isolated from I.
racemosa for insecticidal activity against Spodoptera litura (F.). RESULTS:
Alantolactone and isoalantolactone isolated from I. racemosa exerted growth
inhibitory effects on S. litura. Addition of both the sesquiterpenes to larval
diet extended the development period and reduced pupation as well as adult
emergence. The dietary utilisation experiments on third-instar larvae of S.
litura revealed reduction in consumption and growth rates of larvae as well as
efficiency of conversion of ingested and digested food owing to alantolactone and
isoalantolactone. CONCLUSION: The root extract of I. racemosa, which is rich in
two sesquiterpenes, i.e. alantolactone and isoalantolactone, has the potential
for management of S. litura. However, there is a need to understand the specific
mechanism of action of these compounds. (c) 2016 Society of Chemical Industry.
PMID- 27607233
TI - Psoriatic arthritis treated by anti-TNFs: a monocentric trial of 102 cases in
Auvergne, France.
AB - OBJECTIVES: While several registries have already evaluated the retention of anti
TNF therapy in psoriatic arthritis (PsA), they sometimes reach divergent
conclusions. Our study therefore sought to assess therapeutic retention rates and
predictive factors of response in a patient cohort from Auvergne, France,
followed up in routine clinical practice. METHODS: Medical records of all PsA
patients treated from 2002 to May 2015 were analysed. PsA diagnosis was
established based on the CASPAR criteria. RESULTS: In total, 102 patients were
analysed, comprising 62 men (44.6+/-12.6 years) and 40 women (37.8+/-13.4). Mean
PsA evolution was 2.7 years (0.8-11.2). The most common forms were peripheral
(47/102, 45.1%) and mixed (46/102, 46.1%) PsA. The anti-TNF treatment initiated
was etanercept in 47 cases (45.2%), adalimumab in 29 (27.9%), infliximab in 20
(19.2%), and golimumab in six [5.8%]. In 28 cases (27.4%), anti-TNF was
associated with methotrexate (MTX). Overall, the median duration of anti-TNF
retention was 76.5 months. The hazard ratios (HR) for treatment cessation did not
significantly differ between the etanercept and monoclonal antibody groups
(HR=1.35[0.96-1.93], p=0.08). After 5 years, approximately 30.8% of etanercept
patients and 68.8% of monoclonal antibody patients (adalimumab 71.2%; infliximab
67.2%) were still being treated. Combining with MTX did not prolong the overall
retention rate (HR=0.85[0.37-1.96], p=0.71). Tobacco use was predictive of
discontinuation (p=0.03). CONCLUSIONS: Our study demonstrates good anti-TNF
treatment retention in PsA patients, as well as confirming the deleterious effect
of smoking while providing no argument in favour of combined treatment with MTX
to improve maintenance.
PMID- 27607235
TI - Unilateral Proptosis, Redness, Diplopia, and Numbness in a Young Woman.
PMID- 27607234
TI - Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A
case series of 19 patients.
AB - Xeroderma pigmentosum (XP) is a rare genetic disorder which is divided into eight
complementation groups: XP-A to XP-G and XP-V. Some XP patients demonstrate
severe cutaneous and neurological manifestations, management of which requires
timely diagnosis and intervention. We performed clinical evaluation and genetic
analysis on 19 patients, the largest cohort of XP to date in China. Twenty-three
mutations from six groups were identified, 16 of which were novel. All patients
developed marked freckle-like pigmentation on sun-exposed sites while patients
with XP-A, XP-D, XP-F and XP-G showed acute sunburn reactions. Only XP-A patients
displayed progressive neurological degeneration. A relatively larger proportion
of XP-A and XP-C were found in Chinese XP patients. One XP case and two carriers
were prenatally determined. This study extended the mutation spectrum of XP in
China and may aid in the diagnosis and treatment of Chinese XP patients.
PMID- 27607236
TI - Silencing of Long Non-Coding RNA NONHSAT009968 Ameliorates the Staphylococcal
Protein A-Inhibited Osteogenic Differentiation in Human Bone Mesenchymal Stem
Cells.
AB - BACKGROUND/AIMS: Osteomyelitis is defined as an inflammation of the bones and
bone marrow. The inflammatory microenvironment attenuates the osteogenic
differentiation capacity of stem cells and inhibits osteoblast-mediated bone
formation, leading to net bone loss. However, the whole expression profile,
function and side effect of long non-coding RNAs (lncRNAs) on osteogenic
differentiation of stem cells in an inflammatory microenvironment of
osteomyelitis are not known. METHODS: In the present study, human bone
mesenchymal stem cells (hBMSCs) were treated with different concentrations of
Staphylococcal protein A (SpA) to trigger an inflammatory microenvironment in
vitro to partly duplicate the inflammatory microenvironment of osteomyelitis,
which was confirmed using ELISA for detecting the inflammatory cytokines. The
complete expression profiles of lncRNAs and mRNA during osteogenic
differentiation of hBMSCs in an inflammatory microenvironment triggered by SpA
were analyzed using a lncRNA microarray. LncRNA expression levels were verified
by quantitative reverse transcription PCR analysis (qRT-PCR). The expression of
NONHSAT009968 in hB-MSCs was silenced by infection with lentivirus expressing
NONHSAT009968-shRNA. The expression of Runx2, OCN, OPN, COL1A1, and alkaline
phosphatase (ALP) activity was detected by western blot. Alizarin red staining
and ALP activity detection were carried out. RESULTS: The results of ELISA showed
that SpA treatment induced secretion of inflammatory cytokines IL-1A, IL-6, and
TNFA. The results of alizarin red staining and ALP detection showed that SpA
treatment suppressed the osteogenic differentiation of hBMSCs. A total of 2033
lncRNAs were found with aberrant expression in SpA-treated hBMSCs compared to
controls. Among these lncRNAs, 641 were down-regulated and 1392 were up
regulated. Based on the results of qRT-PCR, lncRNA NONHSAT009968 was chosen for
further investigation. The results of alizarin red staining, ALP activity
detection, and western blot detection of Runx2, OCN, OPN, COL1A1, and ALP
indicated that NONHSAT009968 silencing ameliorates SpA-inhibited osteogenic
differentiation in hBMSCs. CONCLUSION: Our present study provides a basis for
future analyses of the role of lncRNAs in osteoblastic differentiation in an
inflammatory environment triggered by SpA, and lncRNA NONHSAT009968 might be a
new target for promoting osteoblast formation.
PMID- 27607237
TI - Glycoside Hydrolase MoGls2 Controls Asexual/Sexual Development, Cell Wall
Integrity and Infectious Growth in the Rice Blast Fungus.
AB - N-linked glycosylation is a way of glycosylation for newly synthesized protein,
which plays a key role in the maturation and transport of proteins. Glycoside
hydrolases (GHs) are essential in this process, and are involved in processing of
N-linked glycoproteins or degradation of carbohydrate structures. Here, we
identified and characterized MoGls2 in Magnaporthe oryzae, which is a yeast
glucosidase II homolog Gls2 and is required for trimming the final glucose in N
linked glycans and normal cell wall synthesis. Target deletion of MoGLS2 in M.
oryzae resulted in a reduced mycelial growth, an increased conidial production,
delayed conidial germination and loss the ability of sexual reproduction.
Pathogenicity assays revealed that the DeltaMogls2 mutant showed significantly
decreased in virulence and infectious growth. Further studies showed that the
mutant was less sensitive to salt and osmotic stress, and increased sensitivity
to cell wall stresses. Additionally, the DeltaMogls2 mutant showed a defect in
cell wall integrity. Our results indicate that MoGls2 is a key protein for the
growth and development of M. oryzae, involving in the regulation of
asexual/sexual development, stress response, cell wall integrity and infectious
growth.
PMID- 27607238
TI - Vitamin C Inhibits Aggravated Eryptosis by Hydrogen Peroxide in Glucose-6
Phosphated Dehydrogenase Deficiency.
AB - BACKGROUND/AIMS: The study was aimed to investigate if vitamin C could exert
protective effects on development of eryptosis caused by glucose-6-phosphate
dehydrogenase (G6PD) deficiency and hydrogen peroxide. METHODS: Isolated
erythrocytes with different G6PD activity (normal or deficient) were divided into
various groups treated by either Vitamin C or H2O2. Phosphatidylserine (PS)
extroversion rate was detected by Annexin V binding. The intracellular Ca2+
concentration was detected by Fluo3-fluorescence, and western blot was used to
detect the expression of apoptosis factor caspase 3. RESULTS: Compared with the
blank group, the PS extroversion rate (P < 0.001), intracellular Ca2+
concentration (P < 0.001) and active caspase 3 expression level (P < 0.05) of
erythrocytes significantly increased after treatment of 0.05% H2O2. Then the
index of eryptosis significantly decreased after erythrocytes were treated with
Vitamin C (1 mg/ml) for 30 min (all P < 0.05). The decline in erythrocytes with
G6PD normal activity was more significant than those with G6PD deficiency.
CONCLUSION: Vitamin C could effectively inhibit the eryptosis contributed by H2O2
oxidative stress, and the suppression on eryptosis with G6PD normal activity was
more effective than that with G6PD deficiency.
PMID- 27607239
TI - Spotting Epidemic Keystones by R0 Sensitivity Analysis: High-Risk Stations in the
Tokyo Metropolitan Area.
AB - How can we identify the epidemiologically high-risk communities in a
metapopulation network? The network centrality measure, which quantifies the
relative importance of each location, is commonly utilized for this purpose. As
the disease invasion condition is given from the basic reproductive ratio R0, we
have introduced a novel centrality measure based on the sensitivity analysis of
this R0 and shown its capability of revealing the characteristics that has been
overlooked by the conventional centrality measures. The epidemic dynamics over
the commute network of the Tokyo metropolitan area is theoretically analyzed by
using this centrality measure. We found that, the impact of countermeasures at
the largest station is more than 1,000 times stronger compare to that at the
second largest station, even though the population sizes are only around 1.5
times larger. Furthermore, the effect of countermeasures at every station is
strongly dependent on the existence and the number of commuters to this largest
station. It is well known that the hubs are the most influential nodes, however,
our analysis shows that only the largest among the network plays an extraordinary
role. Lastly, we also found that, the location that is important for the
prevention of disease invasion does not necessarily match the location that is
important for reducing the number of infected.
PMID- 27607241
TI - Correction: The Modulation of Mimicry by Ethnic Group-Membership and Emotional
Expressions.
AB - [This corrects the article DOI: 10.1371/journal.pone.0161064.].
PMID- 27607240
TI - "We Are Not Really Marketing Mental Health": Mental Health Advocacy in Zimbabwe.
AB - INTRODUCTION: Few people with mental disorders in low and middle-income countries
(LMICs) receive treatment, in part because mental disorders are highly
stigmatized and do not enjoy priority and resources commensurate with their
burden on society. Advocacy has been proposed as a means of building political
will and community support for mental health and reducing stigma, but few studies
have explored the practice and promise of advocacy in LMICs. METHODS: We
conducted 30 semi-structured interviews with leaders in health and mental health
in Zimbabwe to explore key stakeholder perceptions on the challenges and
opportunities of the country's mental health system. We coded the transcripts
using the constant comparative method, informed by principles of grounded theory.
Few interview questions directly concerned advocacy, yet in our analysis,
advocacy emerged as a prominent, cross-cutting theme across participants and
interview questions. RESULTS: Two thirds of the respondents discussed advocacy,
often in depth, returning to the concept throughout the interview and emphasizing
their belief in advocacy's importance. Participants described six distinct
components of advocacy: the advocates, to whom they advocate ("targets"), what
they advocate for ("asks"), how advocates reach their targets ("access"), how
they make their asks ("arguments"), and the results of their advocacy
("outcomes"). DISCUSSION: Despite their perception that mental health is widely
misunderstood and under-appreciated in Zimbabwe, respondents expressed optimism
that strategically speaking out can reduce stigma and increase access to care.
Key issues included navigating hierarchies, empowering service users to advocate,
and integrating mental health with other health initiatives. Understanding
stakeholder perceptions sets the stage for targeted development of mental health
advocacy in Zimbabwe and other LMICs.
PMID- 27607242
TI - Integrating Domain Specific Knowledge and Network Analysis to Predict Drug
Sensitivity of Cancer Cell Lines.
AB - One of fundamental challenges in cancer studies is that varying molecular
characteristics of different tumor types may lead to resistance to certain drugs.
As a result, the same drug can lead to significantly different results in
different types of cancer thus emphasizing the need for individualized medicine.
Individual prediction of drug response has great potential to aid in improving
the clinical outcome and reduce the financial costs associated with prescribing
chemotherapy drugs to which the patient's tumor might be resistant. In this paper
we develop a network based classifier (NBC) method for predicting sensitivity of
cell lines to anticancer drugs from transcriptome data. In the literature, this
strategy has been used for predicting cancer types. Here, we extend it to
estimate sensitivity of cells from different tumor types to various anticancer
drugs. Furthermore, we incorporate domain specific knowledge such as the use of
apoptotic gene list and clinical dose information in our method to impart
biological significance to the prediction. Our experimental results suggest that
our network based classifier (NBC) method outperforms existing classifiers in
estimating sensitivity of cell lines for different drugs.
PMID- 27607243
TI - A Versatile Method for Fabricating Tissue Engineering Scaffolds with a Three
Dimensional Channel for Prevasculature Networks.
AB - Despite considerable advances in tissue engineering over the past two decades,
solutions to some crucial problems remain elusive. Vascularization is one of the
most important factors that greatly influence the function of scaffolds. Many
research studies have focused on the construction of a vascular-like network with
prevascularization structure. Sacrificial materials are widely used to build
perfusable vascular-like architectures, but most of these fabricated scaffolds
only have a 2D plane-connected network. The fabrication of three-dimensional
perfusable branched networks remains an urgent issue. In this work, we developed
a novel sacrificial molding technique for fabricating biocompatible scaffolds
with a three-dimensional perfusable branched network. Here, 3D-printed poly(vinyl
alcohol) (PVA) filament was used as the sacrificial material. The fused PVA was
deposited on the surface of a cylinder to create the 3D branched solid network.
Gelatin was used to embed the solid network. Then, the PVA mold was dissolved
after curing the hydrogel. The obtained architecture shows good perfusability.
Cell experiment results indicated that human umbilical vein endothelial cells
(HUVECs) successfully attached to the surface of the branched channel and
maintained high viability after a few days in culture. In order to prevent
deformation of the channel, paraffin was coated on the surface of the printed
structure, and hydroxyapatite (HA) was added to gelatin. In conclusion, we
demonstrate a novel strategy toward the engineering of prevasculature thick
tissues through the integration of the fused PVA filament deposit. This approach
has great potential in solving the issue of three-dimensional perfusable branched
networks and opens the way to clinical applications.
PMID- 27607244
TI - A Dyadic Growth Approach to Partner Regulation Attempts on Changes in Drinking
and Negative Alcohol-Related Consequences.
AB - BACKGROUND: Many individuals engage in regulation attempts to manage or reduce
their partner's alcohol use. Research on partner social control behaviors has
shown that regulation attempts generally factor into negative (i.e., punishing)
and positive (i.e., rewarding) dimensions. In the alcohol domain, partner
drinking has been associated with poorer relationship functioning through
punishment. OBJECTIVES: This research applied a dyadic growth model approach to
investigate changes in alcohol consumption and negative alcohol-related
consequences over 6 months, and evaluated whether partner regulation attempts
(punishment and reward) were influential (i.e., successful) in these changes.
METHODS: Married couples (N = 123 dyads) completed web-based measures of partner
regulation attempts, alcohol consumption, and alcohol-related consequences three
times over a 6-month period. RESULTS: Results from dyadic growth curve analyses
showed that partner punishment was significantly associated with increases in
alcohol-related consequences-and marginally associated with increases in alcohol
consumption-over the 6-month period. Partner reward was associated with decreases
in consumption over the study period. These effects were not different for
husbands and wives. Conclusion/Importance: Results support previous research
demonstrating deleterious impact of partner punishing control strategies and
provide important implications for future interventions and treatment.
PMID- 27607245
TI - Chemoselective N-Difluoromethylation of Functionalized Tertiary Amines.
AB - A practical, convenient, and general method for the difluoromethylation of
tertiary amines, using diethyl bromodifluoromethylphosphonate and fluoride, is
described. This commercially available phosphonate smoothly reacts with a
fluoride ion to liberate a difluorocarbene intermediate that in the presence of a
proton source and a tertiary amine generates the corresponding alpha
difluoromethylammonium compound in good to excellent yields. Despite the
involvement of a difluorocarbene intermediate, this difluoromethylation occurs
almost exclusively on the nitrogen atom with diverse molecular structures,
including drugs, surfactants, chiral phase transfer catalysts, polymers, ionic
liquids, and other fine chemicals. A preliminary assessment of the effects that
an alpha-difluoromethyl groupT has on hydrogen bonding and logP of quaternary
ammonium salts is also described.
PMID- 27607246
TI - Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased
Risk for Developing Hypothyroidism in Autoimmune Thyroiditis.
AB - Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is
characterized by cellular and humoral immunity leading to thyroid destruction.
The impact of the humoral immunity on the risk to develop hypothyroidism has not
exactly been defined yet. The aim of the present study was to investigate the
association between thyroid antibody levels and the risk for developing
hypothyroidism. In this retrospective study, 335 untreated AIT patients were
enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg)
antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab
levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels
[p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared
to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and
between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg
Abs alone or in combination with TPO-Abs did not help to increase the sensitivity
to identify patients at risk. Long term follow-up of AIT patients with high TPO
Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range:
2.52+/-2.73 to 3.02+/-3.05 mIU/l; p=0.0420). Still, these patients remained
euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated
with a moderately increased risk of developing hypothyroidism.
PMID- 27607248
TI - Female-Specific Glucose Sensitivity of GnRH1 Neurons Leads to Sexually Dimorphic
Inhibition of Reproduction in Medaka.
AB - Close interaction exists between energy-consuming reproduction and nutritional
status. However, there are differences in costs and priority for reproduction
among species and even between sexes, which leads to diversification of
interactions between reproduction and nutritional status. Despite such
diversified interactions among species and sexes, most of the analysis of the
nutritional status-dependent regulation of reproduction has been limited to an
endothermic vertebrate, mammalian species of either sex. Therefore, the
mechanisms underlying the diversified interactions remain elusive. In the present
study, we demonstrated the effects of malnutritional status on reproduction at
both organismal and cellular levels in an ectothermic vertebrate, a teleost
medaka of both sexes. First, we analyzed the effects of malnutrition by fasting
on gonadosomatic index, number of spawned/fertilized eggs, and courtship
behavior. Fasting strongly suppressed reproduction in females but, surprisingly,
not in males. Next, we analyzed the effects of fasting on firing activity of
hypothalamic GnRH1 neurons, which form the final common pathway for the control
of reproduction. An electrophysiological analysis showed that low glucose, which
is induced by fasting, directly suppresses the firing activity of GnRH1 neurons
specifically in females through intracellular ATP-sensitive potassium channels
and AMP-activated protein kinase pathways. Based on the fact that such
suppressions occurred only in females, we conclude that nutritional status
dependent, glucose-sensing in GnRH1 neurons may contribute to the most fitted
reproductive regulation for each sex.
PMID- 27607247
TI - Single-Step Fabrication of Computationally Designed Microneedles by Continuous
Liquid Interface Production.
AB - Microneedles, arrays of micron-sized needles that painlessly puncture the skin,
enable transdermal delivery of medications that are difficult to deliver using
more traditional routes. Many important design parameters, such as microneedle
size, shape, spacing, and composition, are known to influence efficacy, but are
notoriously difficult to alter due to the complex nature of microfabrication
techniques. Herein, we utilize a novel additive manufacturing ("3D printing")
technique called Continuous Liquid Interface Production (CLIP) to rapidly
prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio,
spacing). This technology allows for mold-independent, one-step manufacturing of
microneedle arrays of virtually any design in less than 10 minutes per patch.
Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate,
polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and
polycaprolactone were fabricated to demonstrate the range of materials that can
be utilized within this platform for encapsulating and controlling the release of
therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and
released the fluorescent drug surrogate rhodamine.
PMID- 27607250
TI - Design and analysis of single-mode tellurite photonic crystal fibers for
stimulated Brillouin scattering based slow-light generation.
AB - We theoretically examine two designs of single-mode (i) Er-doped tellurite and
(ii) undoped tellurite photonic crystal fiber (PCF) for generation of slow light
with tunable features based on stimulated Brillouin scattering. We obtained (i)
Brillouin gain up to 91 dB and time delay of ~145 ns at maximum allowable pump
power of ~775 mW in a 2 m Er-doped tellurite PCF and (ii) Brillouin gain up to
~88 dB and time delay of ~154 ns at maximum allowable pump power ~21 mW in a
100 m undoped tellurite photonic crystal fiber. Simulated results clearly
indicate that the doped tellurite PCF with Er enhances the maximum allowable pump
power and comparable time delay can be obtained even with reduced photonic
crystal fiber length. We believe that the carried out examination and simulation
have potential impact on design and development of slow-light-based photonic
devices applicable in telecommunication systems, enhancement of optical forces,
and quantum computing.
PMID- 27607249
TI - Isolation and characterization of genes encoding leucoanthocyanidin reductase
(FeLAR) and anthocyanidin reductase (FeANR) in buckwheat (Fagopyrum esculentum).
AB - Proanthocyanidins (PAs) are a major group of flavonoids synthesized via the
phenylpropanoid biosynthesis pathway, however the pathway has not been fully
characterized in buckwheat. Anthocyanidin reductase (ANR) and leucoanthocyanidin
reductase (LAR) are involved in the last steps of PA biosynthesis. To isolate the
genes for these enzymes from buckwheat we performed PCR using degenerate primers
and obtained cDNAs of ANR and LAR, which we designated FeANR and FeLAR1. A search
for homologs in a buckwheat genome database with both sequences returned two more
LAR sequences, designated FeLAR2 and FeLAR3. Linkage analysis with an F2
segregating population indicated that the three LAR loci were not genetically
linked. We detected high levels of PAs in roots and cotyledons of buckwheat
seedlings and in buds and flowers of mature plants. FeANR and FeLAR1-3 were
expressed in most organs but had different expression patterns. Our findings
would be useful for breeding and further analysis of PA synthesis and its
regulation in buckwheat.
PMID- 27607251
TI - Low-volume, fast response-time hollow silica waveguide gas cells for mid-IR
spectroscopy.
AB - Hollow silica waveguides (HSWs) are used to produce long path length, low-volume
gas cells, and are demonstrated with quantum cascade laser spectroscopy.
Absorption measurements are made using the intrapulse technique, which allows
measurements to be made across a single laser pulse. Simultaneous laser light and
gas coupling is achieved through the modification of commercially available gas
fittings with low dead volume. Three HSW gas cell configurations with different
path lengths and internal diameters are analyzed and compared with a 30 m path
length astigmatic Herriott cell. Limit of detection measurements are made for the
gas cells using methane at a wavelength 7.82 MUm. The lowest limit of detection
was provided by HSW with a bore diameter of 1000 MUm and a path length of 5 m and
was measured to be 0.26 ppm, with a noise equivalent absorbance of 4.1*10
4. The long-term stability of the HSW and Herriott cells is compared
through analysis of the Allan-Werle variance of data collected over a 24 h
period. The response times of the HSW and Herriott cells are measured to be 0.8 s
and 36 s, respectively.
PMID- 27607252
TI - Performance analysis of an all-optical logic gate based on a single I/Q modulator
with direct detection.
AB - This paper investigates the performance of an all-optical logic gate scheme based
on a single in-phase and quadrature (I/Q) modulator with direct detection. The
proposed scheme of an all-optical logic gate is simple, high speed, and easily
reconfigured to realize 24 logic states by adjusting bias voltages, peak-to-peak
voltages of the driven RF signals, and the phase shift. As the scheme to realize
logic gates is based on the irregular use of a commercially available I/Q
modulator and laser source, a specialized logic gate system including a laser,
I/Q modulator, and driven RF module should be optimally designed to obtain the
best performance. With the system's extinction ratio (ER) and Q-factor as
metrics, the performance of the proposed logic gate scheme is analyzed
theoretically and numerically in this paper. We first give a new theoretical
model of the I/Q modulator. Next, taking the OR gate as an example, the
simulations are carried out to analyze performance under the influence of some
key factors in the system. Results show that the extinction ratio of the whole
system is affected by the phase shift between the two arms of the I/Q modulator
and the extinction ratios of two Mach-Zehnder modulators (MZMs), while Q-factor
is further influenced by the output power of the laser and the insertion loss of
the MZMs in the I/Q modulator. For an I/Q modulator with MZMs having an
extinction ratio of 20 dB, the minimum laser output power to obtain a system's ER
higher than 16 dB is 3 dBm, while in order to obtain a Q-factor higher than 6,
the output power of the laser must not be <10 dBm.
PMID- 27607253
TI - Omnidirectional stereo vision sensor based on single camera and catoptric system.
AB - An omnidirectional stereo vision sensor based on one single camera and catoptric
system is proposed. As crucial components, one camera and two pyramid mirrors are
used for imaging. The omnidirectional measurement towards different directions in
the horizontal field can be performed by four pairs of virtual cameras, with a
consummate synchronism and an improved compactness. Moreover, the perspective
projection invariance is ensured in the imaging process, which avoids the imaging
distortion reflected by the curved mirrors. In this paper, the structure model of
the sensor was established and a sensor prototype was designed. The influences of
the structural parameters on the field of view and the measurement accuracy were
also discussed. In addition, real experiments and analyses were performed to
evaluate the performance of the proposed sensor in the measurement application.
The results proved the feasibility of the sensor, and exhibited a considerable
accuracy in 3D coordinate reconstruction.
PMID- 27607254
TI - Recognition of wall materials through active thermography coupled with numerical
simulations.
AB - In the framework of historical buildings, wall thickness as well as wall
constituents are not often known a priori, and active IR thermography can be
exploited as a nonintrusive method for detecting what kind of material lies
beneath the external plaster layer. In the present work, the wall of a historical
building is subjected to a heating stimulus, and the surface temperature temporal
trend is recorded by an IR camera. A hybrid numerical model is developed in order
to simulate the transient thermal response of a wall made of different known
materials underneath the plaster layer. When the numerical thermal contrast and
the appearance time match with the experimental thermal images, the material
underneath the plaster can be qualitatively identified.
PMID- 27607255
TI - Collimated focal ratio degradation testing for highly multiplexed fiber systems
an improvement to a standard test.
AB - A simple method for determining the focal ratio degradation of optical fibers has
been developed. The method involves splitting the light from the test fiber and
recording ring patterns that have traveled over two different, and known, optical
paths. This new method will be valuable for testing many fibers as will be needed
for new multiobject astronomical spectrographs.
PMID- 27607257
TI - Calibration of line-scan cameras for precision measurement.
AB - Calibration of line-scan cameras for precision measurement should have large
calibration volume and be flexible in the actual measurement field. In this
paper, we present a high-precision calibration method. Instead of using a large
3D pattern, we use a small planar pattern and a precalibrated matrix camera to
obtain plenty of points with a suitable distribution, which would ensure the
precision of the calibration results. The matrix camera removes the necessity of
precise adjustment and movement and links the line-scan camera to the world
easily, both of which enhance flexibility in the measurement field. The method
has been verified by experiments. The experimental results demonstrated that the
proposed method gives a practical solution to calibrate line scan cameras for
precision measurement.
PMID- 27607256
TI - Figure of merit enhancement of surface plasmon resonance sensors using absentee
layer.
AB - By adding an absentee layer on the top of the metallic layer, the figure of merit
(FOM) of a surface plasmon resonance (SPR) sensor with Kretschmann configuration
was enhanced, without changing the resonance angle and the reflectance at the
resonance angle. Comparing with a traditional SPR sensor, the FOM of the SPR
sensor with an absentee layer composed of either 1367 nm thick KCl or 235 nm
thick Si3N4 can be improved by 5.53% or 11.41%,
respectively. The enhancement of the FOM should be attributed to the faster
decrease of the full width at half-maximum than the sensitivity after an absentee
layer was applied in the SPR sensor.
PMID- 27607258
TI - Application of measurement configuration optimization for accurate metrology of
sub-wavelength dimensions in multilayer gratings using optical scatterometry.
AB - Critical dimension measurement accuracy in optical scatterometry relies not only
on the systematic noise level of instruments and the reliability of forward
modeling algorithms, but also heavily on the measurement configuration. To
construct a set of potentially high-accuracy configurations, we apply a general
measurement configuration optimization method based on error propagation theory
and singular value decomposition, by which the measurement accuracy is
approximated as a function of a pseudo Jacobian with respect to the measurement
configurations. Simulations and experiments for the optical metrology of a sub
wavelength deep-etched multilayer grating establish the feasibility of the
proposed method.
PMID- 27607259
TI - Digital sampling Moire as a substitute for microscope scanning Moire for high
sensitivity and full-field deformation measurement at micron/nano scales.
AB - This study proposed to generate digital sampling Moire fringes by two-pixel down
sampling as a substitute for microscope scanning Moire fringes, and further
reconstruct multiplication Moire fringes for micron/nano-scale deformation
measurement. The displacement and strain sensitivities of the proposed
reconstructed multiplication Moire method are 2 times higher in a wide field of
view. Besides, two-dimensional deformation is easily measurable without rotating
the sample stage or the scanning lines, no matter whether the scanning resolution
is adjustable or not. As an example, the deformations of a carbon fiber
reinforced plastic specimen were measured and analyzed. The proposed method
effectively expands the application range of the Moire technique to deformation
measurement.
PMID- 27607260
TI - Gram-Schmidt orthonormalization for retrieval of amplitude images under
sinusoidal patterns of illumination.
AB - Structured illumination using sinusoidal patterns has been used for optical
imaging of biological tissues in biomedical research, and of horticultural
products in food quality evaluation. Implementation of structured-illumination
imaging relies on retrieval of amplitude images, which is conventionally achieved
by a phase-shifting technique that requires collecting a minimum of three phase
shifted images. In this study, we have proposed Gram-Schmidt orthonormalization
(GSO) to retrieve amplitude component (AC) images using only two phase-shifted
images. We have proposed two forms of GSO implementation, and prior to GSO
processing, we eliminated the direct component (DC) background by subtracting a
DC image we recovered using a spiral phase function (SPF) in the Fourier space.
We demonstrated the GSO methods through numerical simulations and application
examples of detection of bruise defects in apples by structured-illumination
reflectance imaging (SIRI). GSO performed comparably to conventional three-phase
based demodulation. It is simple, fast and effective for amplitude retrieval and
requires no prior phase information, which could facilitate fast implementation
of structured-illumination imaging.
PMID- 27607261
TI - Experimental verification of reconstructed absorbers embedded in scattering media
by optical power ratio distribution.
AB - Experimental investigation to show the effectiveness of the extraction method of
absorber information in a scattering medium by taking the output power ratio
distribution is presented. In the experiment, two metallic wires sandwiched by
three homogeneous scattering media are used as absorbers in transmission
geometry. The output power ratio distributions can extract the influence of the
absorbers to enhance the optical signal. The peak position of the output power
ratio distributions agree with the results suggested by numerical simulation.
From the reconstructed results of tomography in the scattering media, we have
confirmed that the tomographic image of two wires can distinguish them
successfully from 41*21 output power ratio distributions by using continuous-wave
light.
PMID- 27607262
TI - All-optical logic gates based on cross phase modulation effect in a phase-shifted
grating.
AB - In this paper, we perform a theoretical study of the all-optical logic gates
based on the techniques of cross phase modulation (XPM) in a phase-shifted
grating. Here the pumps are used to control the switching of a weak continuous
wave (cw). In order to understand the transferring process of the information
from the pump light to the cw light, we first study the switching characteristic
of the device. Then, by changing the combination between two pumps, in a fiber
grating with zero phase shift we have realized NOT, AND, and NAND gates, and in a
phase-shifted grating with the phase shift pi, the other various logic operations
can be realized such as NAND gates and OR gates; when selecting Deltaphi=3/2pi,
we can realize XOR gates and XNOR gates. Thus the change of the phase shift of
the phase-shifted grating will yield various logic gates.
PMID- 27607263
TI - Investigation of SO3 absorption line for in situ gas detection inside
combustion plants using a 4-MUm-band laser source.
AB - We have investigated 4-MUm-band SO3 absorption lines for in
situSO3 detection using a mid-infrared laser source based on
difference frequency generation in a quasi-phase-matched LiNbO3
waveguide. In the wavelength range of 4.09400-4.10600 MUm, there were strong
SO3 absorption lines. The maximum absorption coefficient at a
concentration of 170 ppmv was estimated to be about 3.2*10-5 cm
1 at a gas temperature of 190 degrees C. In coexistence with
H2O, the reduction of the SO3 absorption peak height was
observed, which was caused by sulfuric acid formation. We discuss a method of
using an SO3 equilibrium curve to derive the total SO3
molecule concentration.
PMID- 27607264
TI - Gradient vector fields based on variational image decomposition for
skeletonization of electronic speckle pattern interferometry fringe patterns with
variable density and their applications.
AB - The skeletonization methods based on gradient vector fields (GVFs) have been a
powerful tool for electronic speckle pattern interferometry (ESPI) fringe
patterns. However, the skeletonization of ESPI fringe patterns with variable
density has been an open problem in this area. In this paper, we propose a novel
method for calculating GVFs based on the variational image decomposition of ESPI
fringe patterns with variable density. In the proposed method, the GVFs of low
density regions are described in Beppo-Levi space, the high-density regions in
Hilbert space and the noise regions in curvelet space. The GVFs of a whole image
are the sum of the decomposed GVFs of low-density regions and high-density
regions. The skeletons of ESPI fringe patterns with variable density can be
obtained based on the topological analysis of the GVFs of a whole image. We apply
the proposed method to a computer-simulated and two experimentally obtained ESPI
fringe patterns with variable density and compare them with the related skeleton
methods based on GVFs. The experimental results have demonstrated that the
proposed method outperforms the other methods, even when the quality of the ESPI
fringe patterns is considerably low.
PMID- 27607265
TI - Laser differential fitting confocal microscopy with high imaging efficiency.
AB - Based on the optical arrangement of a bipolar differential confocal microscopy
(BDCM), laser differential fitting confocal microscopy (DFCM) is proposed in this
paper using the feature of BDCM that a zero-crossing point (ZCP) of the axial
response curve precisely corresponds to the focus of the system objective. A
linear segment of the DFCM axial response around the ZCP is used to fit a
straight line. Focus can be determined by solving the equations of the fitting
lines, and then, the sample surface could be measured and reconstructed with a
high resolution. Compared with the curve-fitting peak detection, which is an
algorithm for focus detection widely used in conventional confocal microscopy,
the line-fitting zero solution method used in DFCM has several advantages, such
as high precision and sensitivity. Most importantly, precise focus detection can
be realized using less data, i.e., DFCM has a high measurement efficiency.
Furthermore, DFCM can effectively eliminate common-mode noise in a confocal
microscopy system and has good noise suppression and disturbance resistance
capability.
PMID- 27607266
TI - Design of a monolithic Michelson interferometer for fringe imaging in a near
field, UV, direct-detection Doppler wind lidar.
AB - The low-biased, fast, airborne, short-range, and range-resolved determination of
atmospheric wind speeds plays a key role in wake vortex and turbulence mitigation
strategies and would improve flight safety, comfort, and economy. In this work, a
concept for an airborne, UV, direct-detection Doppler wind lidar receiver is
presented. A monolithic, tilted, field-widened, fringe-imaging Michelson
interferometer (FWFIMI) combines the advantages of low angular sensitivity, high
thermo-mechanical stability, independence of the specific atmospheric conditions,
and potential for fast data evaluation. Design and integration of the FWFIMI into
a lidar receiver concept are described. Simulations help to evaluate the receiver
design and prospect sufficient performance under different atmospheric
conditions.
PMID- 27607267
TI - Common-path optical coherence tomography using a microelectromechanical-system
based endoscopic probe.
AB - This paper presents a common-path (CP) swept-source optical coherence tomography
(SSOCT) system based on a special endoscopic probe design with an in-line
internal reflection as the reference and a two-axis electrothermal
microelectromechanical system mirror for image scanning. The rear surface of a
gradient reflective index (GRIN) lens inside the probe is set as the reference
reflection plane. The length of the GRIN lens is optimized to eliminate the
artifacts in SSOCT images successfully. Doppler OCT is also demonstrated based on
the CP endoscopic probe. The diameter of the probe is only 2.5 mm, so it can be
easily inserted into the biopsy channel of traditional endoscopes to access human
internal organs for in vivo diagnoses.
PMID- 27607268
TI - Structure parameter analysis and uncertainty evaluation for single-camera stereo
digital image correlation with a four-mirror adapter.
AB - Increasing interest in the use of single-camera stereo-digital image correlation
(stereo-DIC) with a four-mirror adapter for full-field three-dimensional shape,
motion, and deformation measurements has led to an ongoing need for both the
optimal design of an optical structure and predictions of the measurement
uncertainties. In this study, to get a clear knowledge of the optical model of
the four-mirror adapter-assisted single-camera stereo-DIC system and further
facilitate an optimal design of the optical structure for specific measurement
objects, comprehensive analyses of the structure parameters, e.g., the baseline
distance and valid field of view of the virtual stereo-DIC system, are conducted.
Based on the law of propagation of uncertainties, the influence of the structure
parameters on the measurement uncertainty is assessed theoretically. The
effectiveness and accuracy of these analyses are verified by calibrating the
single-camera stereo-DIC system and measuring the displacements of a stationary
planar plate.
PMID- 27607269
TI - Extrusion printing for fabrication of spherical and cylindrical microlens arrays.
AB - In this paper, we present an extrusion printing technique for producing spherical
and cylindrical plano-convex microlens arrays with controllable feature
dimensions. This technique employs a robotic adhesive dispenser for robotically
controlled microextrusion of ultraviolet (UV) curable polymer onto a glass
substrate surface to directly deposit the microlens arrays. It provides a simple
and flexible alternative to fabricate both spherical and cylindrical microlens
arrays.
PMID- 27607270
TI - Vibration monitoring of a helicopter blade model using the optical fiber
distributed strain sensing technique.
AB - We demonstrate a dynamic distributed monitoring technique using a long-length
fiber Bragg grating (FBG) interrogated by optical frequency domain reflectometry
(OFDR) that measures strain at a speed of 150 Hz, spatial resolution of 1 mm, and
measurement range of 20 m. A 5 m FBG is bonded to a 5.5 m helicopter blade model,
and vibration is applied by the step relaxation method. The time domain responses
of the strain distributions are measured, and the blade deflections are
calculated based on the strain distributions. Frequency response functions are
obtained using the time domain responses of the calculated deflection induced by
the preload release, and the modal parameters are retrieved. Experimental results
demonstrated the dynamic monitoring performances and the applicability to the
modal analysis of the OFDR-FBG technique.
PMID- 27607271
TI - Oversaturated part-based visual tracking via spatio-temporal context learning.
AB - Partial occlusion is one of the key challenging factors in a robust visual
tracking method. To solve this issue, part-based trackers are widely explored;
most of them are computationally expensive and therefore infeasible for real-time
applications. Context information around the target has been used in tracking,
which was recently renewed by a spatio-temporal context (STC) tracker. The fast
Fourier transform adopted in STC equips it with high efficiency. However, the
global context used in STC alleviates the performance when dealing with
occlusion. In this paper, we propose an oversaturated part-based tracker based on
spatio-temporal context learning, which tracks objects based on selected parts
with spatio-temporal context learning. Furthermore, a structural layout
constraint and a novel model update strategy are utilized to enhance the
tracker's anti-occlusion ability and to deal with other appearance changes
effectively. Extensive experimental results demonstrate our tracker's superior
robustness against the original STC and other state-of-art methods.
PMID- 27607272
TI - Development of an immersive virtual reality head-mounted display with high
performance.
AB - To resolve the contradiction between large field of view and high resolution in
immersive virtual reality (VR) head-mounted displays (HMDs), an HMD monocular
optical system with a large field of view and high resolution was designed. The
system was fabricated by adopting aspheric technology with CNC grinding and a
high-resolution LCD as the image source. With this monocular optical system, an
HMD binocular optical system with a wide-range continuously adjustable
interpupillary distance was achieved in the form of partially overlapping fields
of view (FOV) combined with a screw adjustment mechanism. A fast image processor
centered LCD driver circuit and an image preprocessing system were also built to
address binocular vision inconsistency in the partially overlapping FOV binocular
optical system. The distortions of the HMD optical system with a large field of
view were measured. Meanwhile, the optical distortions in the display and the
trapezoidal distortions introduced during image processing were corrected by a
calibration model for reverse rotations and translations. A high-performance not
fully-transparent VR HMD device with high resolution (1920*1080) and large FOV
[141.6 degrees (H)*73.08 degrees (V)] was developed. The full field-of-view
average value of angular resolution is 18.6 pixels/degree. With the device, high
quality VR simulations can be completed under various scenarios, and the device
can be utilized for simulated trainings in aeronautics, astronautics, and other
fields with corresponding platforms. The developed device has positive practical
significance.
PMID- 27607273
TI - Bidirectional scattering distribution function measurements from volume
diffusers: correction factors and associated uncertainties.
AB - We consider the effect of volume diffusion on measurements of the bidirectional
scattering distribution function when a finite distance is used for the solid
angle defining aperture. We derive expressions for correction factors that can be
used when the reduced scattering coefficients and the index of refraction are
known. When these quantities are not known, the expressions can be used to guide
the assessment of measurement uncertainty. We find that some measurement
geometries reduce the effect of volume diffusion compared to their reciprocal
geometries.
PMID- 27607274
TI - Analytical elimination of substrate backside reflections from reflectance
measurements.
AB - An analytical approach to eliminate substrate backside reflections from measured
reflectance of an unknown optical coating has been deducted. Thereby, measured
transmittance, reflectance, and backside reflectance of the coating and
transmittance and reflectance of the uncoated substrate at the desired angle of
incidence and polarization state are required as input data. In the underlying
theory, layer and substrate materials may be absorbing.
PMID- 27607275
TI - Camera response prediction for various capture settings using the spectral
sensitivity and crosstalk model.
AB - In this paper, a camera response formation model is proposed to accurately
predict the responses of images captured under various exposure settings.
Differing from earlier works that estimated the camera relative spectral
sensitivity, our model constructs the physical spectral sensitivity curves and
device-dependent parameters that convert the absolute spectral radiances of
target surfaces to the camera readout responses. With this model, the camera
responses to miscellaneous combinations of surfaces and illuminants could be
accurately predicted. Thus, creating an "imaging simulator" by using the
colorimetric and photometric research based on the cameras would be of great
convenience.
PMID- 27607276
TI - Large field distributed aperture laser semiactive angle measurement system design
with imaging fiber bundles.
AB - A type of laser semiactive angle measurement system is designed for target
detecting and tracking. Only one detector is used to detect target location from
four distributed aperture optical systems through a 4*1 imaging fiber bundle. A
telecentric optical system in image space is designed to increase the efficiency
of imaging fiber bundles. According to the working principle of a four-quadrant
(4Q) detector, fiber diamond alignment is adopted between an optical system and a
4Q detector. The structure of the laser semiactive angle measurement system is,
we believe, novel. Tolerance analysis is carried out to determine tolerance
limits of manufacture and installation errors of the optical system. The
performance of the proposed method is identified by computer simulations and
experiments. It is demonstrated that the linear region of the system is +/-12
degrees , with measurement error of better than 0.2 degrees . In general, this
new system can be used with large field of view and high accuracy, providing an
efficient, stable, and fast method for angle measurement in practical situations.
PMID- 27607277
TI - Analysis of wavefront coding imaging with cubic phase mask decenter and tilt.
AB - This paper has examined how the decenter and tilt of a cubic phase mask plate
influence the imaging of a wavefront coding system. The calculated phase term of
pupil function with mask decenter and tilt indicates that both decenter and tilt
change the shape of the system modulation transfer function in a predictable way
by changing the phase and defocus parameters. Simulation in an on-axis three
mirror Cassegrain system is presented to confirm the calculated formula result.
Experimental results for mask decenter are also presented. The results
demonstrate that the decenter of a phase mask has less effect on the point spread
function in the z direction than the x and y directions.
PMID- 27607278
TI - Improved system calibration for specular surface measurement by using reflections
from a plane mirror.
AB - In this paper, we introduce a flexible and simple system calibration method for
specular surface metrology based on the combination of reflection rays determined
by the varied points on a screen and reflection images of a plane mirror without
fiducials placed at three different locations. This calibration procedure
involves three steps. The camera is first calibrated based on plane patterns.
Then the reflection ray directions are measured via correspondence matching. The
last calibration step is the pose estimation by the orthogonal iteration
algorithm and reflections in a plane mirror. Basically, the concept of replacing
the coordinates of the camera center with the reflection ray can alleviate the
trouble of imaging aberration. Then global optimization can be operated with the
orthogonal projection defined by the reflection ray, providing precise initial
values for the process of bundle adjustment, compared to the classical
calibration approach directly using the local optimization algorithm. Simulations
and experiments both demonstrate the validity, efficiency, and robustness of the
proposed improved method. In the simulations, the proposed method achieves the
absolute errors of the camera parameters within 3 pixels and the relative errors
of the screen pose are below 0.5% when the noise level is 0.6 pixel. Furthermore,
the calibration method shows strong anti-noise ability, relying on the
application of the reflection rays and the global optimization before the final
bundle adjustment. In addition, the reconstruction accuracy in our experiment
improves by 60.11% by the proposed method compared with the calibration
procedure, which only utilizes the bundle adjustment optimization. In general,
this novel calibration method can make the measurement achieve high accuracy and
robustness at a low cost and with a simple setup, providing an efficient,
economical, and flexible approach for a phase measuring deflectometry system in
practical situations.
PMID- 27607279
TI - Mid-infrared absorption-spectroscopy-based carbon dioxide sensor network in
greenhouse agriculture: development and deployment.
AB - A mid-infrared carbon dioxide (CO2) sensor was experimentally
demonstrated for application in a greenhouse farm environment. An optical module
was developed using a lamp source, a dual-channel pyre-electrical detector, and a
spherical mirror. A multi-pass gas chamber and a dual-channel detection method
were adopted to effectively enhance light collection efficiency and suppress
environmental influences. The moisture-proof function realized by a breathable
waterproof chamber was specially designed for the application of such a sensor in
a greenhouse with high humidity. Sensor structure of the optical part and
electrical part were described, respectively, and related experiments were
carried out to evaluate the sensor performance on CO2 concentration.
The limit of detection of the sensor is 30 ppm with an absorption length of 30
cm. The relative detection error is less than 5% within the measurement range of
30-5000 ppm. The fluctuations for the long-term (10 h) stability measurements on
a 500 ppm CO2 sample and a 2000 ppm CO2 sample are 1.08%
and 3.6%, respectively, indicating a good stability of the sensor. A wireless
sensor network-based automatic monitoring system was implemented for greenhouse
application using multiple mid-infrared CO2 sensor nodes. A monitor
software based on LabVIEW was realized via a laptop for real-time environmental
data display, storage, and website sharing capabilities. A field experiment of
the sensor network was carried out in the town of Shelin in Jilin Province,
China, which proved that the whole monitoring system possesses stable sensing
performance for practical application under the circumstances of a greenhouse.
PMID- 27607280
TI - Refractometer probe based on a reflective carbon nanotube-modified microfiber
Bragg grating.
AB - A carbon nanotube (CNT)-modified microfiber Bragg grating (MFBG) is proposed to
measure the refractive index with a strong enhancement of the sensitivity in the
low refractive index region. The introduction of the CNT layer influences the
evanescent field of the MFBG and causes modification of the reflection spectrum.
With the increase of the surrounding refractive index (SRI), we observe
significant attenuation to the peak of the Bragg resonance, while its wavelength
remains almost unchanged. Our detailed experimental results disclose that the CNT
MFBG demonstrates strong sensitivity in the low refractive index range of 1.333
1.435, with peak intensity up to -53.4 dBm/refractive index unit, which is 15
folds higher than that of the uncoated MFBG. Therefore, taking advantage of the
CNT-induced evanescent field enhancement, the reflective MFBG probe presents
strong sensing capability in biochemical fields.
PMID- 27607281
TI - Ablation threshold and ablation mechanism transition of polyoxymethylene
irradiated by CO2 laser.
AB - Polyoxymethylene (POM) decomposes gradually as it is heated up by the irradiation
of CO2 laser; the long-chain molecules of POM are broken into short
chains, which leads to the lowering of the melting point and the critical
temperature of the ablation products. When the product temperature is above the
melting point, ablation comes up in the way of vaporization; when the product
temperature is higher than the critical temperature, all liquid products are
transformed into gas instantly and the ablation mechanism is changed. The laser
fluence at which significant ablation is observed is defined as the ablation
threshold, and the fluence corresponding to the ablation mechanism changing is
denoted as the flyover threshold. In this paper, random pyrolysis is adopted to
describe the pyrolytic decomposition of POM, and consequently, the components of
the pyrolysis products under different pyrolysis rates are acquired. The Group
Contribution method is used to count the thermodynamic properties of the
pyrolysis products, and the melting point and the critical temperature of the
product mixture are obtained by the Mixing Law. The Knudsen layer relationship is
employed to evaluate the ablation mass removal when the product temperature is
below the critical temperature. The gas dynamics conservation laws associated
with the Jouguet condition are used to calculate the mass removal when the
product temperature is higher than the critical temperature. Based on the model,
a set of simulations for various laser intensities and lengths are carried out to
generalize the relationships between the thresholds and the laser parameters.
Besides the ablated mass areal density, which fits the experimental data quite
well, the ablation temperature, pyrolysis rate, and product components are also
discussed for a better understanding of the ablation mechanism of POM.
PMID- 27607282
TI - Effects of inelastic radiative processes on the determination of water-leaving
spectral radiance from extrapolation of underwater near-surface measurements.
AB - Extrapolation of near-surface underwater measurements is the most common method
to estimate the water-leaving spectral radiance, Lw(lambda) (where
lambda is the light wavelength in vacuum), and remote-sensing reflectance,
Rrs(lambda), for validation and vicarious calibration of satellite
sensors, as well as for ocean color algorithm development. However, uncertainties
in Lw(lambda) arising from the extrapolation process have not been
investigated in detail with regards to the potential influence of inelastic
radiative processes, such as Raman scattering by water molecules and fluorescence
by colored dissolved organic matter and chlorophyll-a. Using radiative transfer
simulations, we examine high-depth resolution vertical profiles of the upwelling
radiance, Lu(lambda), and its diffuse attenuation coefficient,
KLu (lambda), within the top 10 m of the ocean surface
layer and assess the uncertainties in extrapolated values of
Lw(lambda). The inelastic processes generally increase Lu
and decrease KLu in the red and near-infrared (NIR)
portion of the spectrum. Unlike KLu in the blue and green
spectral bands, KLu in the red and NIR is strongly
variable within the near-surface layer even in a perfectly homogeneous water
column. The assumption of a constant KLu with depth that
is typically employed in the extrapolation method can lead to significant errors
in the estimate of Lw. These errors approach ~100% at 900 nm, and the
desired threshold of 5% accuracy or less cannot be achieved at wavelengths
greater than 650 nm for underwater radiometric systems that typically take
measurements at depths below 1 m. These errors can be reduced by measuring
Lu within a much shallower surface layer of tens of centimeters thick
or even less at near-infrared wavelengths longer than 800 nm, which suggests a
requirement for developing appropriate radiometric instrumentation and deployment
strategies.
PMID- 27607283
TI - Optical turbulence in confined media: part I, the indoor turbulence sensor
instrument.
AB - Optical system performances can be affected by local optical turbulence created
by its surrounding environment (telescope dome, clean room, atmospheric surface
layer). We present our new instrument INdoor TurbulENce SEnsor (INTENSE)
dedicated to this local optical turbulence characterization. INTENSE consists of
using several parallel laser beams separated by non-redundant baselines between
0.05 and 2.5 m and measuring the angle of arrival fluctuations from spot
displacements on a CCD. After introducing the theoretical background, we give a
description of the instrument including a detailed characterization of
instrumental noise and, finally, give the first results for the characterization
of the turbulence inside clean rooms for optical systems studies.
PMID- 27607284
TI - Properties of defect-induced multiple pulse laser damage of transmission
components.
AB - When the number of laser pulses increases, the laser-induced damage threshold of
the optical components gradually declines. The magnitude and tendency of this
reduced threshold are associated with various factors. Furthermore, this reduced
threshold is conclusively determined by the limiting factors or defect
characteristics that trigger damage to optical components. Then, fully
understanding the damage properties of different kinds of defects will contribute
to the optimization of the performance and lifetime of the optical components. In
this study, the statistical and deterministic characterizations of the fatigue
effect are used to evaluate the properties of the multiple pulse laser damage of
transmission components. First, the influence of spot sizes and polishing
materials on the properties of the multiple pulse laser damage of optical
components is discussed. Then, the structural, absorptive, and mixed artificial
defects are fabricated, and the damage characteristics are evaluated and
analyzed. Finally, the damage mechanism of different factors has been clarified.
PMID- 27607285
TI - Homodyne laser interferometer involving minimal quadrature phase error to obtain
subnanometer nonlinearity.
AB - The demand for minimal cyclic nonlinearity error in laser interferometry is
increasing as a result of advanced scientific research projects. Research shows
that the quadrature phase error is the main effect that introduces cyclic
nonlinearity error, and polarization-mixing cross talk during beam splitting is
the main error source that causes the quadrature phase error. In this paper, a
new homodyne quadrature laser interferometer configuration based on
nonpolarization beam splitting and balanced interference between two circularly
polarized laser beams is proposed. Theoretical modeling indicates that the
polarization-mixing cross talk is elaborately avoided through nonpolarizing and
Wollaston beam splitting, with a minimum number of quadrature phase error sources
involved. Experimental results show that the cyclic nonlinearity error of the
interferometer is up to 0.6 nm (peak-to-valley value) without any correction and
can be further suppressed to 0.2 nm with a simple gain and offset correction
method.
PMID- 27607286
TI - Compact terahertz wave polarization beam splitter using photonic crystal.
AB - Electromagnetic polarization conveys valuable information for signal processing.
Manipulation of a terahertz wave polarization state exhibits tremendous potential
in developing applications of terahertz science and technology. We propose an
approach to efficiently split transverse-electric and transverse-magnetic
polarized terahertz waves into different propagation directions over the
frequency range from 0.9998 to 1.0007 THz. Both the plane wave expansion method
and the finite-difference time-domain method are used to calculate and analyze
the transmission characteristics of the proposed device. The present device is
very compact and the total size is 1.02 mm*0.99 mm. This polarization beam
splitter performance indicates that the structure has a potential application for
forthcoming terahertz-wave integrated circuit fields.
PMID- 27607287
TI - Extrinsic parameter calibration of stereo vision sensors using spot laser
projector.
AB - The on-site calibration of stereo vision sensors plays an important role in the
measurement field. Image coordinate extraction of feature points of existing
targets is difficult under complex light conditions in outdoor environments, such
as strong light and backlight. This paper proposes an on-site calibration method
for stereo vision sensors based on a spot laser projector for solving the above
mentioned problem. The proposed method is used to mediate the laser spots on the
parallel planes for the purpose of calibrating the coordinate transformation
matrix between two cameras. The optimal solution of a coordinate transformation
matrix is then solved by nonlinear optimization. Simulation experiments and
physical experiments are conducted to validate the performance of the proposed
method. Under the condition that the field of view is approximately 400 mm*300
mm, the proposed method can reach a calibration accuracy of 0.02 mm. This
accuracy value is comparable to that of the method using a planar target.
PMID- 27607288
TI - Design and simulation of a biconic multipass absorption cell for the frequency
stabilization of the reference seeder laser in IPDA lidar.
AB - The design process and simulation method of a multipass absorption cell used for
the frequency stabilization of the reference seeder laser in integrated path
differential absorption (IPDA) lidar are presented. On the basis of the
fundamental theory of the Herriott multipass cell comprising two spherical
mirrors, the initial parameters of the multipass cell, which has an optical path
greater than 10 m and consists of two biconic mirrors, were calculated. More than
30 light spots were distributed on each mirror, and the distance between adjacent
spots was mostly optimized to greater than six times the beam waist. After
optimization, the simulated transmittance spectrum and associated differential
signal were obtained. The interference induced by surface scattering was also
simulated, and its influence on the differential signal was analyzed. A
correspondence between the simulated results and the testing data was observed.
PMID- 27607289
TI - Impacts of field of view configuration of Cross-track Infrared Sounder on clear
sky observations.
AB - Hyperspectral infrared radiance measurements from satellite sensors contain
valuable information on atmospheric temperature and humidity profiles and
greenhouse gases, and therefore are directly assimilated into numerical weather
prediction (NWP) models as inputs for weather forecasting. However, data
assimilations in current operational NWP models still mainly rely on cloud-free
observations due to the challenge of simulating cloud-contaminated radiances when
using hyperspectral radiances. The limited spatial coverage of the 3*3 field of
views (FOVs) in one field of regard (FOR) (i.e., spatial gap among FOVs) as well
as relatively large footprint size (14 km) in current Cross-track Infrared
Sounder (CrIS) instruments limits the amount of clear-sky observations. This
study explores the potential impacts of future CrIS FOV configuration (including
FOV size and spatial coverage) on the amount of clear-sky observations by
simulation experiments. The radiance measurements and cloud mask products (VCM)
from the Visible Infrared Imager Radiometer Suite (VIIRS) are used to simulate
CrIS clear-sky observation under different FOV configurations. The results
indicate that, given the same FOV coverage (e.g., 3*3), the percentage of clear
sky FOVs and the percentage of clear-sky FORs (that contain at least one clear
sky FOV) both increase as the FOV size decreases. In particular, if the CrIS FOV
size were reduced from 14 km to 7 km, the percentage of clear-sky FOVs increases
from 9.02% to 13.51% and the percentage of clear-sky FORs increases from 18.24%
to 27.51%. Given the same FOV size but with increasing FOV coverage in each FOR,
the clear-sky FOV observations increases proportionally with the increasing
sampling FOVs. Both reducing FOV size and increasing FOV coverage can result in
more clear-sky FORs, which benefit data utilization of NWP data assimilation.
PMID- 27607290
TI - Equivalent wavelength self-mixing interferometry for displacement measurement.
AB - In order to improve fringe precision of a self-mixing signal, a simple and
effective method based on an equivalent wavelength self-mixing interferometer is
presented. And a linearization fringe counting method is proposed for equivalent
wavelength self-mixing interferometry to quickly reconstruct target displacement.
The validity of the proposed method was demonstrated by means of simulated
signals and confirmed by several experimental measurements for both harmonic and
aleatory target displacement with a fringe resolution of ~125 nm.
PMID- 27607291
TI - Diffraction efficiency sensitivity to oblique incident angle for multilayer
diffractive optical elements.
AB - The relationship between diffraction efficiency of multilayer diffractive optical
elements (MLDOEs) and arbitrary incident angle was numerically analyzed with the
effective area method. The method is based on the shield effect between two
elements of MLDOEs; a generalized diffraction efficiency formulation was obtained
in a wide range of tilt angles, which overcame the limitations of scalar
diffraction theory when the period width of MLDOEs is taken into account. A
detailed comparison of the proposed effective area method with the scalar
diffraction theory is numerically presented for MLDOEs. The validity of the
proposed method is verified by comparison with the rigorous electromagnetic
analysis method, especially the finite-difference time-domain method. The
analysis results show that the shield effect augments with the increase of the
incident angles; the effect of incident angles on MLDOEs with finite period
widths is more noticeable than that with large period widths.
PMID- 27607292
TI - Dynamic, infrared bandpass filters prepared from polymer-stabilized cholesteric
liquid crystals.
AB - We report on the formulation and electrical control of the position and bandwidth
of reflective bandpass filters prepared from cholesteric liquid crystal (CLC) in
the infrared (3-5 MUm). These filters are prepared from alignment cells employing
infrared transparent electrodes and substrates. The optical nature of the
electrodes is shown to strongly influence the resulting transmission of the
bandpass filters outside of the spectral reflection.
PMID- 27607293
TI - Large-aperture two-dimensional x-ray refractive mosaic lenses.
AB - Lenses with high numerical aperture are required for images with very high
spatial resolution, which is difficult to realize in the x-ray range because of
low-refraction-index decrement and relatively high absorption of x-rays in the
material. However, such an aperture can be realized by means of a mosaic lens, as
shown in this work.
PMID- 27607294
TI - Real-time thermal imaging of solid oxide fuel cell cathode activity in working
condition.
AB - Electrochemical methods such as voltammetry and electrochemical impedance
spectroscopy are effective for quantifying solid oxide fuel cell (SOFC)
operational performance, but not for identifying and monitoring the chemical
processes that occur on the electrodes' surface, which are thought to be strictly
related to the SOFCs' efficiency. Because of their high operating temperature,
mechanical failure or cathode delamination is a common shortcoming of SOFCs that
severely affects their reliability. Infrared thermography may provide a powerful
tool for probing in situ SOFC electrode processes and the materials' structural
integrity, but, due to the typical design of pellet-type cells, a complete
optical access to the electrode surface is usually prevented. In this paper, a
specially designed SOFC is introduced, which allows temperature distribution to
be measured over all the cathode area while still preserving the electrochemical
performance of the device. Infrared images recorded under different working
conditions are then processed by means of a dedicated image processing algorithm
for quantitative data analysis. Results reported in the paper highlight the
effectiveness of infrared thermal imaging in detecting the onset of cell failure
during normal operation and in monitoring cathode activity when the cell is fed
with different types of fuels.
PMID- 27607295
TI - Staircase-scene-based nonuniformity correction in aerial point target detection
systems.
AB - Focal-plane arrays (FPAs) are often interfered by heavy fixed-pattern noise,
which severely degrades the detection rate and increases the false alarms in
airborne point target detection systems. Thus, high-precision nonuniformity
correction is an essential preprocessing step. In this paper, a new nonuniformity
correction method is proposed based on a staircase scene. This correction method
can compensate for the nonlinear response of the detector and calibrate the
entire optical system with computational efficiency and implementation
simplicity. Then, a proof-of-concept point target detection system is established
with a long-wave Sofradir FPA. Finally, the local standard deviation of the
corrected image and the signal-to-clutter ratio of the Airy disk of a Boeing B738
are measured to evaluate the performance of the proposed nonuniformity correction
method. Our experimental results demonstrate that the proposed correction method
achieves high-quality corrections.
PMID- 27607296
TI - Optical algorithm for calculating the quantity distribution of fiber assembly.
AB - A modification of the two-flux model of Kubelka-Munk was proposed for the
description of light propagating through a fiber-air mixture medium, which
simplified fibers' internal reflection as a part of the scattering on the total
fiber path length. A series of systematical experiments demonstrated a higher
consistency with the reference quantity distribution than the common Lambert law
on the fibrogram used in the textile industry did. Its application in the
fibrogram for measuring the cotton fiber's length was demonstrated to be good,
extending its applicability to the wool fiber, the length of which is harder to
measure than that of the cotton fiber.
PMID- 27607297
TI - Ultraviolet (250-550 nm) absorption spectrum of pure water.
AB - Data for the spectral light absorption of pure water from 250 to 550 nm have been
obtained using an integrating cavity made from a newly developed diffuse
reflector with a very high UV reflectivity. The data provide the first scattering
independent measurements of absorption coefficients in the spectral gap between
well-established literature values for the absorption coefficients in the visible
(>400 nm) and UV (<200 nm). A minimum in the absorption coefficient has been
observed in the UV at 344 nm; the value is 0.000811+/-0.000227 m-1.
PMID- 27607298
TI - Design of a holographic tracking module for long-range retroreflector free-space
systems.
AB - Weight reduction and low power consumption are key requirements in the next
generation of unmanned aerial vehicles (UAVs). To communicate with an operator, a
secured link between the UAV and a ground-based station is desirable. To realize
these links, retroreflecting free-space optics is potentially attractive as it
offers light weight and low complexity at the UAV. However, the base station
requires a high-performance tracking module to enable a steady illumination of
the UAV retroreflector. In this paper, we present the design and implementation
of a tracking system, which consists of coarse tracking and holographic fine
tracking modules working cooperatively. Using this system, experimental field
trials were carried out by mounting a multiple-quantum-well-based modulated
retroreflector on a commercial UAV. A 2 Mbps optical link was achieved with a bit
error rate of ~2*10-4 at a link range of 300 m.
PMID- 27607299
TI - Split Hopkinson bar measurement using high-speed full-spectrum fiber Bragg
grating interrogation.
AB - The development and validation of a high-speed, full-spectrum measurement
technique is described for fiber Bragg grating (FBG) sensors. A FBG is surface
mounted to a split-Hopkinson tensile bar specimen to induce high strain rates.
The high strain gradients and large strains that indicate material failure are
analyzed under high strain rates up to 500 s-1. The FBG is
interrogated using a high-speed full-spectrum solid-state interrogator with a
repetition rate of 100 kHz. The captured deformed spectra are analyzed for strain
gradients using a default interior point algorithm in combination with the
modified transfer matrix approach. This paper shows that by using high-speed full
spectrum interrogation of an FBG and the modified transfer matrix method, highly
localized strain gradients and discontinuities can be measured without a direct
line of sight.
PMID- 27607300
TI - Vision-based measurement for rotational speed by improving Lucas-Kanade template
tracking algorithm.
AB - Rotational angle and speed are important parameters for condition monitoring and
fault diagnosis of rotating machineries, and their measurement is useful in
precision machining and early warning of faults. In this study, a novel vision
based measurement algorithm is proposed to complete this task. A high-speed
camera is first used to capture the video of the rotational object. To extract
the rotational angle, the template-based Lucas-Kanade algorithm is introduced to
complete motion tracking by aligning the template image in the video sequence.
Given the special case of nonplanar surface of the cylinder object, a nonlinear
transformation is designed for modeling the rotation tracking. In spite of the
unconventional and complex form, the transformation can realize angle extraction
concisely with only one parameter. A simulation is then conducted to verify the
tracking effect, and a practical tracking strategy is further proposed to track
consecutively the video sequence. Based on the proposed algorithm, instantaneous
rotational speed (IRS) can be measured accurately and efficiently. Finally, the
effectiveness of the proposed algorithm is verified on a brushless direct current
motor test rig through the comparison with results obtained by the microphone.
Experimental results demonstrate that the proposed algorithm can extract
accurately rotational angles and can measure IRS with the advantage of noncontact
and effectiveness.
PMID- 27607301
TI - How many times should a paper be reconsidered?: editorial.
AB - Editor-in-Chief Ron Driggers details the Applied Optics policy of not considering
papers that have been rejected twice by OSA journals.
PMID- 27607302
TI - A new footwear technology to promote non-heelstrike landing and enhance running
performance: Fact or fad?
AB - This study sought to compare the kinetics and kinematics data in a group of
habitual shod runners when running in traditional running shoes and newly
designed minimalist shoes with lug platform. This novel footwear design claims to
simulate barefoot running and reduce energy loss during impact. We compared
footstrike angle (FSA), vertical average (VALR) and instantaneous (VILR) loading
rates, energy loss and initial vertical stiffness between two shoe conditions.
Runners demonstrated a decreased FSA while running in minimalist shoes with lug
platform than traditional shoes (P = 0.003; Cohen's d = 0.918). However, we did
not observe a landing pattern transition. VALR and VILR between two footwear
conditions showed no significant difference (P = 0.191-0.258; Cohen's d = 0.304
0.460). Initial vertical stiffness (P = 0.032; Cohen's d = 0.671) and energy loss
(P = 0.044; Cohen's d = 0.578) were greater when running in minimalist shoes with
lug platform. The results show that minimalist shoes with lug platform reduce the
FSA but may not lead to a landing pattern switch or lower vertical loading rates.
Interestingly, the new shoe design leads to a greater energy loss than
traditional running shoes, which could be explained by a higher initial vertical
stiffness.
PMID- 27607303
TI - Accelerometer-based determination of gait variability in older adults with knee
osteoarthritis.
AB - Knee osteoarthritis (KOA) can affect the spatiotemporal (ST) aspects of gait as
well as the variability of select ST parameters based on standard linear measures
of variability (e.g., standard deviation (SD) and coefficient of variation). Non
linear measures (e.g., fractal scaling index (FSI) and sample entropy) can be
more sensitive to changes in gait variability, and have been used to quantify
differences in the stride patterns of patients with Parkinson's disease and the
motion of ACL-deficient knees. However, the effect of KOA on the dynamic
complexity of the stride pattern has not been investigated. Therefore, the
purpose of this study was to investigate the effect of KOA on gait variability
(linear and non-linear measures) in a group of older adults, and to compare these
results to a healthy control group. Participants walked for 10min with a tri
axial accelerometer placed at the lower back. Mean and SDs of stride time and
step time as well as the FSI for the entire series of stride times were
calculated for each participant. Participants with KOA had significantly greater
mean stride time (p=0.031) and step time (p=0.024) than control group
participants. While stride and step time variability (SD) were greater in the KOA
group, the differences were not significant, nor was the difference in the FSI.
Low statistical power (beta=0.40 and 0.30 for stride and step time SD,
respectively) combined with the confounding effects of walking speed and
heterogeneous KOA severity likely prevented significant differences from being
found.
PMID- 27607304
TI - Effects of age and physical activity status on redistribution of joint work
during walking.
AB - During walking older adults rely less on ankle and more on hip work than young
adults. Disproportionate declines in plantarflexor strength may be a mechanism
underlying this proximal work redistribution. We tested the hypothesis that
proximal redistribution is more apparent in older compared to young adults and in
sedentary compared to active individuals over multiple walking speeds. We
recruited 18 young (18-35 yrs) and 17 older (65-80 yrs) physically active and
sedentary adults. Participants completed five trials at four walking speeds as
marker positions and ground reaction forces were collected. Sagittal plane net
joint moments were computed using inverse dynamics. Instantaneous joint powers
for the ankle, knee, and hip were computed as products of net joint moments and
joint angular velocities. Positive joint work was computed by integrating hip,
knee, and ankle joint powers over time in early, mid, and late stance,
respectively. Relative joint work was expressed as a percentage of total work.
Isokinetic strength of lower limb flexor and extensor muscles was measured. Older
adults had lower relative ankle (p=0.005) and higher relative hip (p=0.007) work
than young adults for multiple speeds. Non-significant trends (p<0.10) indicating
sedentary participants had lower relative ankle (p=0.068) and higher relative hip
work (p=0.087) than active adults were observed. Age-related differences in
plantarflexor strength were not disproportionate compared to strength differences
in knee and hip musculature. Age influenced proximal work redistribution over
multiple walking speeds. Physical activity status showed a similar trend for
proximal work redistribution, but failed to reach statistical significance.
PMID- 27607306
TI - A mononuclear non-heme-iron dioxygen-carrying protein?
AB - The ability of mononuclear non-heme iron complexes to function as molecular
oxygen transporters is investigated by density functional theory. The factors
governing the efficiency of the reversible binding of dioxygen at the active site
of the dinuclear non-heme iron enzyme hemerythrin, including antiferromagnetic
coupling and the conversion of dioxygen to hydroperoxo by a proton coupled 2
electron transfer mechanism, are revisited and considered as possible tools in
mononuclear non-heme complexes. Several mononuclear non-heme model complexes,
including active sites of enzymes already known to interact with dioxgenic
ligands, are constructed and the molecular oxygen transportation capabilities of
these complexes are examined computationally. The high-spin nature of the ground
state of these complexes implies an intrinsic kinetic lability of the oxy
structures, as also evident from potential energy surface calculations towards
iron-dioxygen cleavage. Proton affinities as calibrated with reference compounds
showed that these complexes are highly unlikely to undergo protonation to form
hydroperoxo-like adducts. Mixed superoxo descriptions of the dissociated
dioxygenic ligands in all complexes add to the overall conclusion that these
model structures are significantly disadvantaged in any attempt to be employed
for molecular oxygen transportation.
PMID- 27607305
TI - Complete mitochondrial genome of javeline goby (Synechogobius hasta).
AB - In this study, we cloned and sequenced the complete mitochondrial DNA (mtDNA) of
Synechogobius hasta to characterize and compare their mitochondrial genomes. The
total length of the mitochondrial genome is 16,655 bp with an accession number
KM891736. The organization of the mitochondrial genomes was similar to those
reported from other fish mitochondrial genomes containing 37 genes (13 protein
coding genes, 2 ribosomal RNA and 22 transfer RNAs) and a major non-coding
control region. Except for ND6 and 8 tRNAs, all other genes are encoded on the
heavy strand. The base composition of the 13 mitochondrial protein-coding genes
in the third position was relatively low (9.7%). The complete mitogenome may
provide important date set for the study of genetic mechanism of S. hasta.
PMID- 27607307
TI - Preparation and characterization of a novel highly hydrophilic and antifouling
polysulfone/nanoporous TiO2 nanocomposite membrane.
AB - In this research, novel ultrafiltration nanocomposite membranes were prepared by
incorporating self-synthesized nanoporous titanium dioxide (NTiO2) nanoparticles
into polysulfone. The surface of the nanoparticle was treated with a silane-based
modifier to improve its distribution in the host polymer. Atomic-force
microscopy, scanning electron microscopy, Fourier transform infrared
spectroscopy, Brunauer-Emmett-Teller, transmission electron microscopy, energy
dispersive x-ray spectroscopy, porosity and contact angle tests were conducted to
characterize the properties of the particles as well as the fabricated
nanocomposite membranes. The effects of the nanoparticle incorporation were
evaluated by conducting ultrafiltration experiments. It was reported that the
membrane pure water flux was increased with increasing NTiO2 loading owing to the
high porosity of the nanoparticles embedded and/or formation of enlarged pores
upon addition of them. The antifouling capacity of the membranes was also tested
by ultrafiltration of bovine serum albumin fouling solution. It was found that
both water flux and antifouling capacity tended to reach desired level if the
NTiO2 added was at optimized loading.
PMID- 27607308
TI - UVER and UV index at high altitude in Northwestern Argentina.
AB - Measurements of ultraviolet erythemal radiation (UVER) made during two years at
three sites located at altitudes over 1000ma.s.l. in Northwestern Argentina
(Salta, San Carlos, and El Rosal) have been used to estimate and analyze the UV
Index (UVI) and the cumulative doses at these locations. For the UVER irradiance,
data of January (maximum values) and June (minimum values) have been analyzed as
representative of the year for all locations. The UVI reaches extreme (>11)
values in >20% of the analyzed days in Salta (1190ma.s.l.), while these are
reached in San Carlos (1611ma.s.l.) and El Rosal (3355ma.s.l.) in >40% of the
analyzed days. Finally, the cumulative doses over an average year have also been
studied for each location. The doses received during austral summer and autumn
are of the same order, and represent one third of the annual dose, while the
doses received during austral winter and spring represent one sixth of the annual
dose approximately.
PMID- 27607311
TI - A Systematic Review of Cross-cultural Adaptation of the Oswestry Disability
Index.
AB - STUDY DESIGN: Systematic review of cross-cultural adaptation of the Oswestry
Disability Index (ODI). OBJECTIVE: The aim of this study was to evaluate the
translation procedures for and measurement properties of cross-cultural
adaptations of the ODI. SUMMARY OF BACKGROUND DATA: The ODI is the most commonly
used questionnaire to determine the outcome of low back pain, and has been
translated into many other languages, such as Danish, Greek, and Korean, and
adapted for use in different countries. METHODS: PubMed, the Cochrane Library,
Medline, and EMBASE were searched from the time they were established to January
2015. Studies related to cross-cultural adaptation of the ODI in a specific
language/culture were included. Guidelines for the Process of Cross-Cultural
Adaptation of Self-Report Measures and Quality Criteria for Psychometric
Properties of Health Status Questionnaire were used for assessment. RESULTS: This
study included 27 versions of ODI adaptations in 24 different languages/cultures.
Only the Danish-Danish adaptation employed all six of the cross-cultural
adaptation processes. Expert committee review (three of 27), back translation
(eight of 27), and pretesting (nine of 27) were conducted in very few studies.
The Polish-Polish (two) adaptation reported all (nine of nine) the measurement
properties, whereas the Traditional Chinese-Taiwan and Hungarian-Hungarian
adaptations reported six of them. Content validity (16/27), construct validity
(17/27), and reliability (22/27) were determined in a relatively high number of
studies, whereas agreement (three of 27), responsiveness (12/27), floor and
ceiling effects (six of 27), and interpretability (one of 27) were only
determined in some studies. CONCLUSION: We recommend the Traditional Chinese
Taiwan, Simplified Chinese-Mandarin Chinese, Danish-Danish, German-Swiss,
Hungarian-Hungarian, Italian-Italian, and Polish-Polish (two) versions for
application, but Traditional Chinese-Hong Kong, French-Swiss, Japanese-Japanese
(two), Polish-Polish (two), Tamil-Indian, and Thai-Thai versions may need more
research. Furthermore, supplementary tests for the adaptations are necessary,
especially for assessing agreement, responsiveness, and interpretability. LEVEL
OF EVIDENCE: 1.
PMID- 27607312
TI - Epidemiological Characteristics of Traumatic Spinal Cord Injury in Guangdong,
China.
AB - STUDY DESIGN: A hospital-based retrospective epidemiological study. OBJECTIVE:
The aim of this study was to examine the demographic and epidemiological
characteristics of patients with traumatic spinal cord injury (TSCI) in Guangdong
to help health-related institutions develop measures to determine the best
allocation of medical resources. SUMMARY OF BACKGROUND DATA: TSCI is a highly
disabling and deadly injury. Currently, there is little information regarding the
epidemiological characteristics for TSCI in Guangdong. METHODS: We
retrospectively reviewed the medical records of partial second-grade class-A
hospitals (mainly capturing general city and county hospitals and some large
scale affiliated hospitals) in Guangdong province according to the International
Classification of Disease Version 10 (ICD-10) and diagnostic code of TSCI.
RESULTS: The study included the medical records of 1340 patients with TSCI, and
the annual number of TSCI admissions increased during the 2003 to 2011 period.
The male-to-female ratio was approximately 3.5:1. The major causes of spinal cord
injuries were high falls (41.0%) and traffic accidents (37.8%). The most common
injury among patients with TSCI was cervical injury (818 cases). In addition,
62.9% of the patients had spinal fractures, 24.0% had other fractures, and 13.7%
had brain injuries. Furthermore, 25.1% (337/1340) of the patients experienced
clinical complications. The differences in the number of patients with and
without complete injury who accepted surgery and hyperbaric oxygen therapy were
statistically significant (P < 0.05), and the difference in total medical cost
was significant (P < 0.05). CONCLUSION: There are specific epidemiological
characteristics of TSCI patients in Guangdong, and preventive measures are
suggested to focus on high-risk populations, such as adult men. LEVEL OF
EVIDENCE: 3.
PMID- 27607313
TI - Human Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck
Squamous Cell Carcinoma-Reply.
PMID- 27607314
TI - What do stakeholders need to implement shared decision making in routine cancer
care? A qualitative needs assessment.
AB - BACKGROUND: Shared decision making (SDM) is particularly relevant in oncology,
where complex treatment options with varying side effects may lead to meaningful
changes in the patient's quality of life. For several years, health policies have
called for the implementation of SDM, but SDM remains poorly implemented in
routine clinical practice. Implementation science has highlighted the importance
of assessing stakeholders' needs to inform the development of implementation
programs. Thus, the aim of the present study was to assess different
stakeholders' needs regarding the implementation of SDM in routine care. MATERIAL
AND METHODS: A qualitative study using focus groups and interviews was conducted.
Focus groups were carried out with junior physicians, senior physicians, nurses
and other healthcare providers (HPCs) (e.g. psycho-oncologists,
physiotherapists), patients and family members. Head physicians as well as other
HPCs in management positions were interviewed. Audiotapes of focus groups and
interviews were transcribed verbatim and analyzed using content analysis.
RESULTS: Six focus groups with a total of n = 42 stakeholders as well as n = 17
interviews were conducted. Focus groups and interviews revealed five main
categories of needs to be fulfilled in order to achieve a better implementation
of SDM in routine cancer care: 1) changes in communication, 2) involvement of
other parties, 3) a trustful patient-physician relationship, 4) culture change
and 5) structural changes. Stakeholders discussed four clusters of intervention
strategies that could foster the implementation of SDM in routine cancer care: 1)
clinician-mediated interventions, 2) patient-mediated interventions, 3) provision
of patient information material and 4) the establishment of a patient advocate.
CONCLUSION: Study results show that stakeholders voiced a diversity of needs to
foster implementation of SDM in routine cancer care, of which some can be
directly addressed by intervention strategies. Present results can be used to
develop an implementation program to foster SDM in routine cancer care.
PMID- 27607315
TI - Effects of glucose-lowering drugs on cardiovascular outcomes in patients with
type 2 diabetes.
PMID- 27607316
TI - Educating the West in the use of magnifying narrow-band imaging for colorectal
tumors.
PMID- 27607317
TI - Vascular tumors and malformations in children, Introduction.
AB - Over the past decade, I have been amazed at the growth in the field of vascular
anomalies. The recognition of vascular birthmarks as a defined area of medicine
is a relatively recent event. The International Society for the Study of Vascular
Anomalies (ISSVA) was founded by Drs John Mulliken and Anthony Young in the late
1970s. Mulliken and Glowacki's sentinel 1982 paper on the biologic classification
of vascular anomalies further established the field, by providing clarity of
nomenclature and unifying concepts that had previously been lacking.
PMID- 27607318
TI - Infantile hemangiomas, complications and treatments.
AB - Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. While
the majority regress without the need for intervention, approximately 10%, often
site dependent, can cause serious complications and require treatment. IH
complications can be categorized as life threatening, obstructive, ulcerative or
disfiguring. Life threatening complications include airway and hepatic IHs.
Functional complications obstructing vital structures or impairing function
include periocular, nasal, labial, parotid, auricular, and breast IHs. Local
complications arise from ulceration or those in cosmetically sensitive areas.
Therapeutic options for complicated IHs include pharmacologic (topical or
systemic), surgical, or laser interventions. Topical agents are best employed for
small, superficial, and localized IHs; while systemic therapy is reserved for
larger IHs and those with more aggressive growth characteristics with propranolol
as first-line therapy.
PMID- 27607319
TI - Infantile hemangiomas and structural anomalies: PHACE and LUMBAR syndrome.
AB - In a subset of patients, infantile hemangiomas may be associated with structural
anomalies. Structural anomalies may affect the upper body (PHACE Syndrome) or the
lower body (LUMBAR Syndrome). Since their initial descriptions, improved
understanding of these two syndromes has lead to recognition of a broader
phenotypic spectrum than initially recognized. This paper aims to provide an
updated review of the presentation, associated anomalies, and management of PHACE
and LUMBAR syndromes, two well-characterized syndromes associated with IH.
PMID- 27607320
TI - Congenital hemangiomas.
AB - Congenital hemangiomas are rare solitary vascular tumors that do not proliferate
after birth. They are characterized as either rapidly involuting congenital
hemangiomas (RICHs) or noninvoluting congenital hemangiomas (NICHs) based on
their clinical progression. NICHs have no associated complications, but are
persistent. RICH, while usually asymptomatic, may ulcerate or bleed early in
their presentation, but involute quickly during the first few months of life.
Hepatic RICHs are not associated with cutaneous RICHs, but may result in high
output cardiac failure due to arteriovenous or portovenous shunting. In the
following review, the clinical characteristics and current management specific to
congenital hemangiomas is discussed.
PMID- 27607321
TI - Genetic basis for vascular anomalies.
AB - The fundamental genetics of many isolated vascular anomalies and syndromes
associated with vascular anomalies have been elucidated. The rate of discovery
continues to increase, expanding our understanding of the underlying
interconnected molecular pathways. This review summarizes genetic and clinical
information on the following diagnoses: capillary malformation, venous
malformation, lymphatic malformation, arteriovenous malformation, PIK3CA-related
overgrowth spectrum (PROS), Proteus syndrome, SOLAMEN syndrome, Sturge-Weber
syndrome, phakomatosis pigmentovascularis, congenital hemangioma, verrucous
venous malformation, cutaneomucosal venous malformation, blue rubber bleb nevus
syndrome, capillary malformation-arteriovenous malformation syndrome, Parkes
Weber syndrome, and Maffucci syndrome.
PMID- 27607322
TI - Histopathology of vascular anomalies: update based on the revised 2014 ISSVA
classification.
AB - Precise diagnosis of childhood vascular anomalies is challenging, and requires
careful correlation of clinical findings, diagnostic imaging, histopathology and
genetic analysis. Skin and soft tissue biopsies remain an important element in
the complete evaluation of many vascular anomalies included in the revised 2014
International Society for the Study of Vascular Anomalies (ISSVA) classification.
Here we present an overview of the light microscopic and immunohistochemical
features of the entities in this updated classification scheme, with emphasis on
newly-included diagnoses such as PTEN hamartoma of soft tissue.
PMID- 27607323
TI - The clinical spectrum of kaposiform hemangioendothelioma and tufted angioma.
AB - Kasposiform hemoangioendothelioma (KHE) and tufted angioma (TA) are classifed as
vascular tumors with locally aggressive and benign growth potential,
respectively, within the classification schema proposed by the International
Society for the Study of Vascular Anomalies. A unique feature of these vascular
tumors is the risk of Kasabach-Merritt phenomenon (KMP), a severe
thrombocytopenia with mild to moderate coagulopathy resulting from intralesional
platelet trapping. As with many vascular anomalies, accurate description of
clinical course, responses to therapy, and long-term outcomes have been hindered
by lesion misidentification, imprecise nomenclature, and lack of prospective,
randomized clinical trials to assess therapeutic efficacy. The classic
dermatologic features of these lesions can facilitate diagnosis for the astute
provider; however, the absence of or unusual integumentary involvement or
presentation in a less common age group (adolescents/adults) poses a diagnostic
challenge. Current approaches to the management of KHE/TA are often informed by
lesion features such as presence of KMP, extent and location of the tumor, and
symptomatology. Evidence-based treatment guidelines are limited. Corticosteroids,
vincristine, interferon, multi-agent regimens and newer therapies, such as
sirolimus, have demonstrated efficacy in patient series. The use of surgical
excision and interventional radiology guided therapies have been described with
mixed clinical benefit. Collaboration among emerging vascular anomaly centers and
an increasing number of providers across subspecialties with interest in this
field are facilitating the development of standardized approaches to diagnosis
and management. The rarity of KHE-spectrum lesions and the heterogeneity of
clinical manifestations necessitate rationally designed, multisite clinical
trials to investigate risk stratification schemas and formally evaluate the short
and long-term efficacy of available and novel therapies.
PMID- 27607324
TI - Multifocal vascular lesions.
AB - Multifocal vascular lesions are important to recognize and appropriately
diagnose. Generally first noticed on the skin, multifocal vascular lesions may
have systemic involvement. Distinguishing among the different types of multifocal
vascular lesions is often based on clinical features; however, radiological
imaging and/or biopsy are frequently needed to identify distinct features and
guide treatment. Knowledge of the systemic associations that can occur with
different vascular anomalies may reduce life-threatening complications, such as
coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review
provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and
treatment of several well-recognized multifocal vascular tumors and
malformations.
PMID- 27607325
TI - Overgrowth syndromes with vascular malformations.
AB - This review provides a clinically-oriented summary of the most commonly
encountered overgrowth syndromes associated with vascular malformations. This
manuscript will outline morphologic features, clinical evaluation and management
of this complex group of patients. Recent genetic advances have aided in
classification and help to explain overlapping clinical features in many cases.
PMID- 27607326
TI - Vascular anomalies: differential diagnosis and mimickers.
AB - Vascular anomalies are very common in children and encompass a wide spectrum of
diseases. Many vascular anomalies can be mistaken for infantile hemangioma (IH).
In addition, there is a variety of rare disorders including benign and malignant
tumors that may mimic IH and other types of vascular anomalies. Understanding the
clinical features, natural history, and typical clinical course of different
types of vascular anomalies is essential in order to make the correct diagnosis
and guide management. Radiologic imaging plays an important role in establishing
the diagnosis; and when the diagnosis remains in doubt, a biopsy performed by a
surgical specialist with expertise may prove to be lifesaving.
PMID- 27607328
TI - From prison to the streets: Can importation work in reverse?
AB - The purpose of this study was to determine whether prison misconduct is capable
of predicting rearrest and whether criminal thinking plays a role in this
relationship. Two hypotheses, a variable-centered hypothesis and a person
centered hypothesis, were tested in a group of 951 male federal inmates, with
results showing that at the variable level, prison misconduct predicted arrests
for more serious crimes (person offenses) but not for less serious crimes
(nonperson offenses). In an effort to examine the prison misconduct-community
recidivism relationship at the person level, latent class growth analysis (LCGA)
was performed on offending indicators across 3 nonoverlapping time periods:
before prison (prior convictions), in prison (annual rate of incident reports),
and after prison (total subsequent arrests). The LCGA results revealed a large
decelerating pattern and 3 smaller accelerating patterns. Criminal thinking
successfully distinguished between the 2 patterns after controlling for age and
criminal history. The present findings suggest that prison can have a deterrent
effect (decelerating pattern) or a criminogenic effect (accelerating patterns)
after a person's release from prison and that criminal thinking may put one at
risk for entry into the accelerating pattern. (PsycINFO Database Record
PMID- 27607327
TI - Medical management of vascular anomalies.
AB - We have entered an exciting era in the care of patients with vascular anomalies.
These disorders require multidisciplinary care and coordination and dedicated
centers have emerged to address this need. Vascular tumors have been treated with
medical therapies for many years, while malformations have been historically
treated with endovascular and operative procedures. The recent serendipitous
discoveries of propranolol and sirolimus for vascular anomalies have
revolutionized this field. In particular, sirolimus responses are challenging the
dogma that vascular malformations are not biologically active. While initially
explored for lymphatic anomalies, sirolimus is now being used broadly throughout
the spectrum of vascular anomalies. Whether medical therapies are reserved for
refractory patients or used first line is currently dependent on the experience
and availability of alternative therapies at each institution. On the horizon, we
anticipate new drugs targeting genes and pathways involved in vascular anomalies
to be developed. Also, combinations of medications and protocols combining
medical and procedural approaches are in development for refractory patients.
PMID- 27607329
TI - Factors Affecting Adherence to Statins in Hypercholesterolemic Kuwaiti Patients:
A Cross-Sectional Study.
AB - OBJECTIVE: This study examined statin adherence amongst Kuwaiti
hypercholesterolemic patients in order to identify factors associated with poor
adherence and to determine whether or not an association exists between statin
adherence and the risk profile of coronary heart disease (CHD). SUBJECTS AND
METHODS: Two hundred hypercholesterolemic patients (30-69 years of age) were
recruited from Kuwaiti primary healthcare clinics and interviewed about
demographic characteristics, pre-existing self-reported medical conditions and
prescribed medications. The Morisky Medication Adherence Scale was used to assess
statin adherence (a self-reported, medication-adherence questionnaire divided
into 3 levels, with a score of 8 denoting high adherence, 6 to <8 denoting medium
adherence and <6 denoting low adherence). Data regarding anthropometric,
psychological and serum risk factors were collected using 2 additional
questionnaires, laboratory tests and bioelectrical impedance scales. Binary
logistic regression was used to determine predictors of adherence and general
linear modelling was used to test relationships between continuous outcomes and
statin adherence. RESULTS: Of the 200 participants, 117 (58.5%) reported low
adherence, 83 (41.5%) reported medium adherence and no patients (0%) scored high
adherence. Younger patients (aged 30-50 years) had lower adherence than older
patients (>50 years) [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.01
1.09] for every extra year; p < 0.01). Those without diabetes, i.e. 113 (56.5%),
were less likely to report medium adherence than those with diabetes (OR 0.42;
95% CI 0.23-0.75; p < 0.01). Low statin adherence was associated with higher
levels of plasma cholesterol (p < 0.001) and low-density lipoprotein (p < 0.01).
CONCLUSION: In this study, there was a high prevalence of low statin adherence,
especially among younger patients with fewer concomitant diseases. The results
indicated an inverse relationship between statin adherence and CHD risk profile.
PMID- 27607331
TI - Whole body-element composition of Atlantic salmon Salmo salar influenced by
migration direction and life stage in three distinct populations.
AB - Body-element content was measured for three life stages of wild Atlantic salmon
Salmo salar from three distinct Newfoundland populations as individuals crossed
between freshwater and marine ecosystems. Life stage explained most of the
variation in observed body-element concentration whereas river of capture
explained very little variation. Element composition of downstream migrating post
spawn adults (i.e. kelts) and juvenile smolts were similar and the composition of
these two life stages strongly differed from adults migrating upstream to spawn.
Low variation within life stages and across populations suggests that S. salar
may exert rheostatic control of their body-element composition. Additionally,
observed differences in trace element concentration between adults and other life
stages were probably driven by the high carbon concentration in adults because
abundant elements, such as carbon, can strongly influence the observed
concentrations of less abundant elements. Thus, understanding variation among
individuals in trace elements composition requires the measurement of more
abundant elements. Changes in element concentration with ontogeny have important
consequences the role of fishes in ecosystem nutrient cycling and should receive
further attention.
PMID- 27607330
TI - Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt,
November 2007-November 2014.
AB - BACKGROUND: Influenza typically comprises a substantial portion of acute
respiratory infections, a leading cause of mortality worldwide. However,
influenza epidemiology data are lacking in Egypt. We describe seven years of
Egypt's influenza hospitalizations from a multi-site influenza surveillance
system. METHODS: Syndromic case definitions identified individuals with severe
acute respiratory infection (SARI) admitted to eight hospitals in Egypt.
Standardized demographic and clinical data were collected. Nasopharyngeal and
oropharyngeal swabs were tested for influenza using real-time reverse
transcription polymerase chain reaction and typed as influenza A or B, and
influenza A specimens subtyped. RESULTS: From November 2007-November 2014,
2,936/17,441 (17%) SARI cases were influenza-positive. Influenza-positive
patients were more likely to be older, female, pregnant, and have chronic
condition(s) (all p<0.05). Among them, 53 (2%) died, and death was associated
with older age, five or more days from symptom onset to hospitalization, chronic
condition(s), and influenza A (all p<0.05). An annual seasonal influenza pattern
occurred from July-June. Each season, the proportion of the season's influenza
positive cases peaked during November-May (19-41%). CONCLUSIONS: In Egypt,
influenza causes considerable morbidity and mortality and influenza SARI
hospitalization patterns mirror those of the Northern Hemisphere. Additional
assessment of influenza epidemiology in Egypt may better guide disease control
activities and vaccine policy.
PMID- 27607333
TI - QuickStats: Percentages* of Residential Care Communities and Adult Day Services
Centers That Provided(?) Selected Services - United States, 2014.
AB - In 2014, a greater percentage of residential care communities than adult day
service centers provided five of seven selected services. The majority of
residential care communities provided pharmacy services (82%); followed by
transportation for social activities (79%); physical, occupational, or speech
therapy (69%); hospice (62%); skilled nursing (59%); and mental health services
(52%). Fewer than half provided social work services (48%). The majority of adult
day services centers provided transportation for social activities (69%); skilled
nursing (66%); and social work (52%). %). Fewer than half provided physical,
occupational, or speech therapy (49%). One third or less provided mental health
(33%), pharmacy (27%), and hospice services (12%).
PMID- 27607332
TI - Sex-based influence on clinical outcomes after drug-eluting stent implantation in
real-world patients: insight from the FOCUS registry.
AB - OBJECTIVES: To investigate the impact of sex on clinical outcomes after drug
eluting stent (DES) implantation in real-world patients. METHODS AND RESULTS: A
total number of 4720 patients (3365 males and 1355 females) undergoing the second
generation cobalt-chromium sirolimus-eluting stent (CoCr-SES) implantation from
the FOCUS registry were included in this analysis. The cumulative incidences of
major adverse cardiovascular event (MACE) (1.5% vs. 2.4%; p = .03),
cardiovascular death (0.5% vs. 1.0%; p = .02) and target vessel revascularization
(TVR) (0.3% vs. 0.8%; p = .01) within six months were significantly higher in
females and the risks of MACE (adjusted hazard ratio [HR] 0.5 (0.3-0.9); p = .01)
and TVR (adjusted HR 0.1(0.0-0.5); p = .001) remained significant in multivariate
analysis. Reversely, the cumulative incidences of MACE (5.4% vs. 4.8%; p = .04)
and any revascularization (5.1% vs. 3.3%; p = .01) were significantly higher in
males beyond six months and the risks of all-cause death (adjusted HR 1.6 (1.1
2.5); p = .03) and cardiovascular death (adjusted HR 1.9 (1.1-3.6); p = .03)
turned out to be significant in multivariate analysis. Notes: All cumulative
incidences were presented as male vs. female; all HRs were calculated as male
relative to female. CONCLUSIONS: Females were associated with higher risk of
early adverse events, while, males were associated with higher risk of late
adverse events. Key messages Females undergoing PCI are typically older, have
more cardiovascular risk factors, while, males in need of PCI are more frequently
associated with complex lesions. The overall three-year cumulative incidences of
adverse events are not significantly different between males and females but
numerically higher in males. Females are associated with significantly higher
risks of MACE and TVR within six months, while, males are associated with
significantly higher risk of all-cause mortality and cardiac mortality beyond 6
months.
PMID- 27607334
TI - MicroRNA-320a Strengthens Intestinal Barrier Function and Follows the Course of
Experimental Colitis.
AB - BACKGROUND: Inflammatory bowel disease is a chronic-remittent disorder with the
risk of disabling complications due to uncontrolled inflammation. Accurate
biomarkers are needed to noninvasively monitor the disease course to tailor
therapy. We evaluated the potential of the specific microRNA (miR)-320a to
monitor disease activity in experimental colitis or patients with Crohn's disease
and investigated its functional role in intestinal epithelial barrier formation.
METHODS: The impact of miR-320a on intestinal barrier function was tested in
vitro in T84 epithelial cells by transepithelial resistance measurement and
quantitative real-time polymerase chain reaction analysis on inflammatory and
microbial stimulation. Experimental colitis was studied in dextran sodium sulfate
colitis, T-cell transfer colitis, and IL-10 mice. Disease course was monitored by
body weight measurement, colonoscopy, and histological examination. MiR-320a
expression during inflammation was assessed in T84 cells, murine blood, and
colonic tissue and in peripheral blood from patients with Crohn's disease with
active or quiescent disease. RESULTS: MiR-320a transfection of T84 cells
reinforced barrier integrity reflected by increased transepithelial resistance (P
< 0.01) and inhibited barrier-destructive enteropathogenic Escherichia coli
effects resulting in increased tight junction protein JAM-A expression (P = 0.02)
and decrease of barrier integrity-destabilizing miR-320a target PPP2R5B (P <
0.001). Tumor necrosis factor-alpha and interleukin-1beta stimulation increased a
miR-320a epxression in T84 cells. MiR-320a level was increased in blood samples
from colitic mice and patients with Crohn's disease showing a strong correlation
with disease activity (r = 0.67). CONCLUSIONS: MiR-320a strengthens intestinal
barrier function in vitro and has the potential to monitor disease activity of
colitic mice. Future studies are needed to further evaluate the potential of miR
320a in patients with inflammatory bowel disease.
PMID- 27607335
TI - Preoperative Anti-tumor Necrosis Factor Therapy in Patients with Ulcerative
Colitis Is Not Associated with an Increased Risk of Infectious and Noninfectious
Complications After Ileal Pouch-anal Anastomosis.
AB - BACKGROUND: There are conflicting data regarding the effect of previous exposure
to anti-tumor necrosis factor (anti-TNF) therapy on complication rates after
pelvic pouch surgery for patients with ulcerative colitis (UC). In particular,
there is concern surrounding the rates of pouch leaks and infectious
complications, including pelvic abscesses, in anti-TNF-treated subjects who
require ileal pouch-anal anastomosis (IPAA) surgery. METHODS: A retrospective
study was performed in UC subjects who underwent IPAA between 2002 and 2013.
Demographic data, clinical data, use of anti-TNF therapy, steroids,
immunosuppressants, and surgical outcomes were assessed. RESULTS: Seven hundred
seventy-three patients with UC/IPAA were reviewed. Fifteen patients were excluded
from the analysis because of missing data. There were 196 patients who were
exposed to anti-TNF therapy and 562 patients who were not exposed to anti-TNF
therapy preoperatively. There were no significant differences in the
postoperative IPAA leak rate between those exposed to anti-TNF therapy and the
control group (n = 26 [13.2%] versus 66 [11.7%], respectively, P = 0.44). In
addition, there were no significant differences in the postoperative 2-stage IPAA
leak rate in those who had been operated on within 15 days from the last anti-TNF
dose (n = 10), within 15 to 30 days (n = 17), or 31 to 180 days (n = 54) (10%,
5.9%, and 14.8% respectively, P = 0.43) nor were there differences based on the
presence of detectable infliximab serum levels. CONCLUSIONS: Preoperative anti
TNF therapy in patients with UC is not associated with an increased risk of
infectious and noninfectious complications after IPAA including pelvic abscesses,
leaks, and wound infections.
PMID- 27607337
TI - Boosting Solar Cell Photovoltage via Nanophotonic Engineering.
AB - Approaching the theoretically limiting open circuit voltage (Voc) of solar cells
is crucial to optimize their photovoltaic performance. Here, we demonstrate
experimentally that nanostructured layers can achieve a fundamentally larger
Fermi level splitting, and thus a larger Voc, than planar layers. By etching
tapered nanowires from planar indium phosphide (InP), we directly compare planar
and nanophotonic geometries with the exact same material quality. We show that
the external radiative efficiency of the nanostructured layer at 1 sun is
increased by a factor 14 compared to the planar layer, leading to a 70 mV
enhancement in Voc. The higher voltage arises from both the enhanced outcoupling
of photons, which promotes radiative recombination, and the lower active material
volume, which reduces bulk recombination. These effects are generic and promise
to enhance the efficiency of current record planar solar cells made from other
materials as well.
PMID- 27607336
TI - Antibiotic Treatment Induces Long-lasting Changes in the Fecal Microbiota that
Protect Against Colitis.
AB - BACKGROUND: The interplay between host genetics, immunity, and microbiota is
central to the pathogenesis of inflammatory bowel disease. Previous population
based studies suggested a link between antibiotic use and increased inflammatory
bowel disease risk, but the mechanisms are unknown. The purpose of this study was
to determine the long-term effects of antibiotic administration on microbiota
composition, innate immunity, and susceptibility to colitis, as well as the
mechanism by which antibiotics alter host colitogenicity. METHODS: Wild-type mice
were given broad-spectrum antibiotics or no antibiotics for 2 weeks, and
subsequent immunophenotyping and 16S rRNA gene sequencing-based analysis of the
fecal microbiome were performed 6 weeks later. In a separate experiment, control
and antibiotic-treated mice were given 7 days of dextran sulfate sodium, 6 weeks
after completing antibiotic treatment, and the severity of colitis scored
histologically. Fecal transfer was performed from control or antibiotic-treated
mice to recipient mice whose endogenous microbiota had been cleared with
antibiotics, and the susceptibility of the recipients to dextran sulfate sodium
induced colitis was analyzed. Naive CD4 T cells were transferred from control and
antibiotic-treated mice to immunodeficient Rag-1 recipients and the severity of
colitis compared. RESULTS: Antibiotics led to sustained dysbiosis and changes in
T-cell subpopulations, including reductions in colonic lamina propria total T
cells and CD4 T cells. Antibiotics conferred protection against dextran sulfate
sodium colitis, and this effect was transferable by fecal transplant but not by
naive T cells. CONCLUSIONS: Antibiotic exposure protects against colitis, and
this effect is transferable with fecal microbiota from antibiotic-treated mice,
supporting a protective effect of the microbial community.
PMID- 27607338
TI - Greater Omental Milky Spot Examination for Diagnosis of Peritoneal Metastasis in
Gastric Cancer Patients.
AB - OBJECTIVE: To evaluate the diagnostic value of cytological greater omental milky
spot examination for the diagnosis of peritoneal metastasis in gastric cancer
patients. METHODS: A total of 136 patients diagnosed with gastric cancer and
without distant metastasis were enrolled in our study. All patients underwent
laparoscopy and CH40 suspension liquid dye of peritoneal lymph nodes
preoperatively as well as ascites or peritoneal lavage fluid collections and
excisions of marked greater omental milky spot tissues perioperatively. RESULTS:
According to the laparoscopic results, the patients were divided into T1-T2 stage
(n = 56) without and into T3-T4 stage (n = 80) with tumor invasion into the
serosal layer. Among the T1-T2-stage patients, tumor cells could be detected in
peritoneal lavage fluids in 2 cases, whereas with greater omental milky spot
examination, peritoneal metastasis was detected in 8 cases. Among the 80 cases in
the T3-T4 stage, tumor cells could be detected in 28 cases via peritoneal lavage
cytology and in 43 cases by greater omental milky spot examinations, and 4 cases
had cancer cell infiltration also in nonmilky spot omental areas. The statistical
analysis showed that the staging accuracy rate of exfoliative cytology
examination was superior to that of the laparoscopic exploration (P < .05), but
its sensitivity was significantly lower than that obtained with cytological
greater omental milky spot examinations (P < .05). CONCLUSIONS: The laparoscopic
exploration could make a preliminary diagnosis of peritoneal metastasis via
serosal layer invasion detection. For further analyses, cytological examinations
of greater omental milky spots were more sensitive than exfoliative cytology.
PMID- 27607339
TI - Imaging via complete cantilever dynamic detection: general dynamic mode imaging
and spectroscopy in scanning probe microscopy.
AB - We develop and implement a multifrequency spectroscopy and spectroscopic imaging
mode, referred to as general dynamic mode (GDM), that captures the complete
spatially- and stimulus dependent information on nonlinear cantilever dynamics in
scanning probe microscopy (SPM). GDM acquires the cantilever response including
harmonics and mode mixing products across the entire broadband cantilever
spectrum as a function of excitation frequency. GDM spectra substitute the
classical measurements in SPM, e.g. amplitude and phase in lock-in detection.
Here, GDM is used to investigate the response of a purely capacitively driven
cantilever. We use information theory techniques to mine the data and verify the
findings with governing equations and classical lock-in based approaches. We
explore the dependence of the cantilever dynamics on the tip-sample distance, AC
and DC driving bias. This approach can be applied to investigate the dynamic
behavior of other systems within and beyond dynamic SPM. GDM is expected to be
useful for separating the contribution of different physical phenomena in the
cantilever response and understanding the role of cantilever dynamics in dynamic
AFM techniques.
PMID- 27607340
TI - Spectrum of immune-mediated necrotizing myopathies and their treatments.
AB - PURPOSE OF REVIEW: This review aims to describe the spectrum of clinical,
histological, and serological features in patients with immune-mediated
necrotizing myopathies (IMNMs). RECENT FINDINGS: Autoantibodies recognizing the
signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase
(HMGCR) define two unique subtypes of necrotizing myositis patient with distinct
clinical features. For example, the major histocompatibility class II human
leukocyte antigen allele DRB111:01 is a strong immunogenetic risk factor for
developing anti-HMGCR autoantibodies whereas B5001 and DQA10104 are over
represented in patients with anti-SRP autoantibodies. Furthermore, statin
exposure is a risk factor only for anti-HMGCR autoantibodies. And while skeletal
muscle involvement is predominant in most patients with both autoantibodies, lung
involvement appears in ~20% of anti-SRP-positive patients but is more rare in
anti-HMGCR-positive patients. Of note, ~20% of anti-SRP and anti-HMGCR positive
patients have significant lymphocytic infiltrates on muscle biopsy and thus would
not be formally categorized as having IMNM; aside from this, these patients are
clinically indistinguishable from other patients with the same autoantibody
profile. SUMMARY: Anti-SRP and anti-HMGCR autoantibodies define unique
populations of IMNM patients. It may be more appropriate to subtype myositis
patients based on these autoantibodies than on their muscle biopsy features.
PMID- 27607341
TI - Bariatric surgery in managing diabetes mellitus.
AB - PURPOSE OF REVIEW: Obesity is a worldwide epidemic, having profound effects on
Western populations. Bariatric surgery has long been employed to treat obesity
and its related comorbidities. Over time, researchers have amassed significant
data to support bariatric surgery in the pursuit of treating diabetes mellitus.
This review serves to introduce the most recent findings and their relation to
the various bariatric surgical options as bariatric surgery will continue to
cement itself in the treatment paradigm of diabetes mellitus. RECENT FINDINGS:
Numerous studies performed in the past 10 years have demonstrated the improvement
or cessation of diabetes with bariatric surgical intervention. In comparing the
vertical sleeve gastrectomy and Roux-en-Y gastric bypass, data demonstrate a more
beneficial response of diabetes to the Roux-en-Y gastric bypass, and an even
further exaggerated response with the biliopancreatic diversion/duodenal switch.
The benefit has long been established, but what causes the improvement in
diabetes mellitus after bariatric surgery? Recent data suggest a decrease in
circulating bile salts as well as changes to inflammatory markers and circulating
cytokines. Furthermore, tailoring of existing surgical procedures has led to the
development of the SIPS procedure, and its benefit is demonstrated in bypassing a
large portion of intestine while eliminating an enteroenterostomy, helping to
reduce short gut syndrome and resultant diarrhea. SUMMARY: The surgical climate
within the bariatric field is changing and will continue to do so in the future.
As the understanding of the causes or mechanisms in which bariatric surgery
improves metabolic disorders becomes more evident, the process of individualizing
care for specific patients will become more prevalent.
PMID- 27607342
TI - Endoscopic treatment of obesity.
AB - PURPOSE OF REVIEW: Obesity and its comorbid illnesses affect millions worldwide
and are one of the major causes of preventable death in the world. Bariatric
surgery is currently offered to individuals with a BMI greater than 40 kg/m or
greater than 35 kg/m with obesity-related comorbidities such as hypertension or
diabetes. Endoscopic bariatric therapies, with their reduced invasiveness and
potential reversibility, may complement surgical approaches for achieving weight
loss. RECENT FINDINGS: At the time of this writing, two endoscopically placed
intragastric balloons and an endoscopically placed aspiration tube have been
approved by the Food and Drug Administration for weight loss purposes. Some
devices employ a suturing platform to create plications or to appose two
surfaces. Other endoscopic strategies under investigation to treat obesity
related comorbidities such as diabetes include duodenal mucosal resurfacing and
creation of a partial jejunoileal diversion using self-assembling magnets.
SUMMARY: Current endoscopic methods for the treatment of obesity utilize various
mechanisms, including occupying gastric volume, reducing gastric capacity,
altering caloric absorption, or aspirating gastric contents. The long-term
outcomes and cost-effectiveness of these strategies remain to be fully
elucidated. The landscape of endoscopic bariatric therapies continues to evolve.
PMID- 27607343
TI - Gastric acid secretion.
AB - PURPOSE OF REVIEW: The present review summarizes the past year's literature, both
clinical and basic science, regarding neuroendocrine and intracellular regulation
of gastric acid secretion and proper use of antisecretory medications. RECENT
FINDINGS: Gastric acid kills microorganisms, modulates the gut microbiome,
assists in digestion of protein, and facilitates absorption of iron, calcium, and
vitamin B12. The main stimulants of acid secretion are gastrin, released from
antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and
acetylcholine, released from antral and oxyntic intramural neurons. Other
stimulants include ghrelin, motilin, and hydrogen sulfide. The main inhibitor of
acid secretion is somatostatin, released from oxyntic and antral D cells.
Glucagon-like peptide-1 also inhibits acid secretion. Proton pump inhibitors
(PPIs) reduce acid secretion and, as a result, decrease somatostatin and thus
stimulate gastrin secretion. Although considered well tolerated drugs, concerns
have been raised this past year regarding associations between PPI use and kidney
disease, dementia, and myocardial infarction; the quality of evidence, however,
is very low. SUMMARY: Our understanding of the physiology of gastric secretion
and proper use of PPIs continues to advance. Such knowledge is crucial for
improved management of acid-peptic disorders.
PMID- 27607344
TI - Bridging the Time Gap: A Copper/Zinc Oxide/Aluminum Oxide Catalyst for Methanol
Synthesis Studied under Industrially Relevant Conditions and Time Scales.
AB - Long-term stability of catalysts is an important factor in the chemical industry.
This factor is often underestimated in academic testing methods, which may lead
to a time gap in the field of catalytic research. The deactivation behavior of an
industrially relevant Cu/ZnO/Al2 O3 catalyst for the synthesis of methanol is
reported over a period of 148 days time-on-stream (TOS). The process was
investigated by a combination of quasi in situ and ex situ analysis techniques.
The results show that ZnO is the most dynamic species in the catalyst, whereas
only slight changes can be observed in the Cu nanoparticles. Thus, the
deactivation of this catalyst is driven by the changes in the ZnO moieties. Our
findings indicate that methanol synthesis is an interfacially mediated process
between Cu and ZnO.
PMID- 27607345
TI - Protective Role of GPER Agonist G-1 on Cardiotoxicity Induced by Doxorubicin.
AB - The use of Doxorubicin (Dox), a frontline drug for many cancers, is often
complicated by dose-limiting cardiotoxicity in approximately 20% of patients. The
G-protein estrogen receptor GPER/GPR30 mediates estrogen action as the
cardioprotection under certain stressful conditions. For instance, GPER
activation by the selective agonist G-1 reduced myocardial inflammation, improved
immunosuppression, triggered pro-survival signaling cascades, improved myocardial
mechanical performance, and reduced infarct size after ischemia/reperfusion (I/R)
injury. Hence, we evaluated whether ligand-activated GPER may exert
cardioprotection in male rats chronically treated with Dox. 1 week of G-1 (50
MUg/kg/day) intraperitoneal administration mitigated Dox (3 mg/kg/day) adverse
effects, as revealed by reduced TNF-alpha, IL-1beta, LDH, and ROS levels. Western
blotting analysis of cardiac homogenates indicated that G-1 prevents the increase
in p-c-jun, BAX, CTGF, iNOS, and COX2 expression induced by Dox. Moreover, the
activation of GPER rescued the inhibitory action elicited by Dox on the
expression of BCL2, pERK, and pAKT. TUNEL assay indicated that GPER activation
may also attenuate the cardiomyocyte apoptosis upon Dox exposure. Using ex vivo
Langendorff perfused heart technique, we also found an increased systolic
recovery and a reduction of both infarct size and LDH levels in rats treated with
G-1 in combination with Dox respect to animals treated with Dox alone.
Accordingly, the beneficial effects induced by G-1 were abrogated in the presence
of the GPER selective antagonist G15. These data suggest that GPER activation
mitigates Dox-induced cardiotoxicity, thus proposing GPER as a novel
pharmacological target to limit the detrimental cardiac effects of Dox treatment.
J. Cell. Physiol. 232: 1640-1649, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27607346
TI - Pneumococcal vaccinations effectively prevent blood culture-negative infections
that resemble occult pneumococcal bacteraemia or bacteraemic pneumococcal
pneumonia at one to 36 months of age.
AB - AIM: The occurrence of blood culture-positive pneumococcal bacteraemia and
bacteraemic pneumonia decreased after large-scale pneumococcal vaccinations were
introduced. The aim of this study was to evaluate the effect of pneumococcal
vaccinations on hospitalisations due to blood culture-negative infections with
fever and leucocytosis, without any other focus than pneumonic infiltration.
MATERIAL: This was a retrospective hospital chart review covering the
prevaccination era of 2008-2009 and postvaccination era of 2012-2013. The number
of study subjects with fever and blood leucocytosis of >17.5 * 10E9/L at one to
36 months of age was 202. RESULTS: The incidence of hospitalisation for
infections associated with fever and leucocytosis, when pneumonic infiltration
was present on the chest radiograph, was 4.7/10 000/year, with a 95% confidence
interval (95% CI) of 2.2-8.8 in children under 36 months in 2012-2013. When
pneumonic infiltration was not present, the respective incidence was 14.6/10
000/year (95% CI: 9.6-21.1). The figure from the 2008-2009 prevaccination era was
11.3 (95% CI: 8.1-15.3) when pneumonic infiltration was present and 24.0/10
000/year (95% CI: 19.2-29.7) when pneumonic infiltration was absent. CONCLUSION:
This study provides evidence of the effectiveness of pneumococcal vaccinations in
preventing blood culture-negative infections that resembled occult pneumococcal
bacteraemia (pneumococcaemia) or bacteraemic pneumococcal pneumonia at one to 36
months of age.
PMID- 27607347
TI - Sexual pain in women: exploring the manifestations of vaginismus versus
vulvodynia.
AB - BACKGROUND: Sexual pain is frequently seen in gynecological practice as a
consequence of lower tract pathology. When organic causes are ruled out, we must
think of a functional pain syndrome such as the genital pelvic pain/penetration
disorder (GPPD). Vaginismus and vulvodynia require different treatments. Even if
gynecologists do not usually manage functional sexual pain, they can easily reach
the differential diagnosis through the sexual pain anamnesis, because some
symptoms are specific of one or the other condition. METHODS: To verify our
hypothesis we retrospectively evaluated the clinical records of 44 women affected
by functional sexual pain. The words patients, used to describe their pain, were
categorized in the following symptoms: dyspareunia, burning pain, stabbing pain,
dryness, itching, and obstacle to penetration, each coded as present or absent.
RESULTS: The unsupervised cluster analysis of the reported symptoms identified
two groups: 19 out of 20 women were clinically diagnosed as having vaginismus,
while the second group included all the 24 women clinically diagnosed with
vulvodynia, plus one vaginismic patient. CONCLUSIONS: The high adherence between
clinical and statistical findings supports that the differential diagnosis
between vaginismus and vulvodynia can be reached on the basis of the elements
collected during intake, including pain history.
PMID- 27607349
TI - Colour in digital pathology: a review.
AB - Colour is central to the practice of pathology because of the use of coloured
histochemical and immunohistochemical stains to visualize tissue features. Our
reliance upon histochemical stains and light microscopy has evolved alongside a
wide variation in slide colour, with little investigation into the implications
of colour variation. However, the introduction of the digital microscope and
whole-slide imaging has highlighted the need for further understanding and
control of colour. This is because the digitization process itself introduces
further colour variation which may affect diagnosis, and image analysis
algorithms often use colour or intensity measures to detect or measure tissue
features. The US Food and Drug Administration have released recent guidance
stating the need to develop a method of controlling colour reproduction
throughout the digitization process in whole-slide imaging for primary diagnostic
use. This comprehensive review introduces applied basic colour physics and colour
interpretation by the human visual system, before discussing the importance of
colour in pathology. The process of colour calibration and its application to
pathology are also included, as well as a summary of the current guidelines and
recommendations regarding colour in digital pathology.
PMID- 27607348
TI - Vitamin D Deficiency and Glycemic Status in Children and Adolescents with Type 1
Diabetes Mellitus.
AB - BACKGROUND: Vitamin D (25OHD) effects on glycemic control are unclear in children
and adolescents with type 1 diabetes. Aims of this study were to investigate
25OHD status among children with T1DM and its relationship with insulin
sensitivity and glycemic status. SUBJECTS AND METHODS: A cross sectional study
was carried out between 2008-2014. A total of 141 patients had a T1DM >12 months
diagnosis and were enrolled in the present study. Of these 35 (24.8%) were
migrants and 106 (75.2%) Italians (T2). We retrospectively analyzed data at the
onset of the disease (T0)(64 subjects) and 12-24 months before the last visit
(T1,124 subjects). Fasting glucose, glycated hemoglobin (HbA1c), 25OHD levels and
daily insulin requirement were evaluated and Cholecalciferol 1000 IU/day
supplementation for the management of vitamin D insufficiency (<75 nmol/L) was
systematically added. RESULTS: A generalized 25OHD insufficiency was found at
each study time, particularly in migrants. At T0, the 25OHD levels were inversely
related to diabetic keto-acidosis (DKA) severity (p<0.05). At T1 and T2, subjects
with 25OHD <=25nmol/L (10 ng/mL) showed higher daily insulin requirement (p<0.05)
and HbA1c values (p<0.01) than others vitamin D status. The 25OHD levels were
negatively related with HbA1c (p<0.001) and daily insulin dose (p<0.05) during
follow up. There was a significant difference in 25OHD (p<0.01) between subjects
with different metabolic control (HbA1c <7.5%,7.5-8%,>8%), both at T1 and T2. In
supplemented subjects, we found a significant increase in 25OHD levels (p<0.0001)
and decrease of HbA1c (p<0.001) between T1 and T2, but this was not significant
in the migrants subgroup. Multivariate regression analysis showed a link between
HbA1c and 25OHD levels (p<0.001). CONCLUSIONS: Children with T1DM show a
generalized 25OHD deficiency that impact on metabolic status and glycemic
homeostasis. Vitamin D supplementation improves glycemic control and should be
considered as an additional therapy.
PMID- 27607350
TI - Characterization of the Translationally Controlled Tumor Protein (TCTP)
Interactome Reveals Novel Binding Partners in Human Cancer Cells.
AB - Translationally controlled tumor protein (TCTP) is a highly conserved
housekeeping protein present in eukaryotic organisms. It is involved in
regulating many fundamental processes and plays a critical role in tumor
reversion and tumorigenesis. Increasing evidence suggests that TCTP plays a role
in the regulation of cell fate determination and is a promising therapeutic
target for cancer. To decipher the exact mechanisms by which TCTP functions and
how all these functions are integrated, we analyzed the interactome of TCTP in
HeLa cells by coimmunoprecipitation (IP) and mass spectrometry (MS). A total of
98 proteins were identified. We confirmed the in vitro and in vivo association of
TCTP with six of the identified binding proteins using reciprocal IP and
bimolecular fluorescence complementation (BiFC) analysis, respectively. Moreover,
TCTP interacted with Y-box-binding protein 1 (YBX1), and their interaction was
localized to the N-terminal region of TCTP and the 1-129 amino acid (aa) residues
of YBX1. The YBX1 protein plays an important role in cell proliferation, RNA
splicing, DNA repair, drug resistance, and stress response to extracellular
signals. These data suggest that the interaction of TCTP with YBX1 might
cooperate or coordinate their functions in the control of diverse regulatory
pathways in cancer cells. Taken together, our results not only reveal a large
number of TCTP-associated proteins that possess pleiotropic functions, but also
provide novel insights into the molecular mechanisms of TCTP in tumorigenesis.
PMID- 27607351
TI - Hypoxia-Inducible Factor-1alpha Activates the Transforming Growth Factor
beta/SMAD3 Pathway in Kidney Tubular Epithelial Cells.
AB - BACKGROUND: Kidney injury, including chronic kidney disease and acute kidney
injury, is a worldwide health problem. Hypoxia and transforming growth factor
beta (TGF-beta) are well-known factors that promote kidney injury. Hypoxia
inducible factor (HIF) and SMAD3 are their main downstream transcriptional
factors. Hypoxia-HIF pathway and TGF-beta/SMAD3 pathway play a crucial role in
the progression of kidney injury. However, reports on their interactions are
limited, and the global transcriptional regulation under their control is almost
unknown. METHODS: Kidney tubular epithelial cells were cultured and stimulated by
hypoxia and TGF-beta. We detected global binding sites of HIF-1alpha and SMAD3 in
cells using chromatin immunoprecipitation-sequencing (ChIP-Seq), and measured the
gene expression using RNA-sequencing (RNA-Seq). ChIP-quantitative PCR (qPCR) was
used to quantitatively evaluate bindings of SMAD3. RESULTS: ChIP-Seq revealed
that 2,065 and 5,003 sites were bound by HIF-1alpha and SMAD3, respectively, with
614 sites co-occupied by both factors. RNA-Seq showed that hypoxia and TGF-beta
stimulation causes synergistic upregulation of 249 genes, including collagen type
I alpha 1 (COL1A1) and serpin peptidase inhibitor, clade E, member 1, which are
well-known to be involved in fibrosis. Ontology of the 249 genes implied that the
interaction of HIF-1alpha and SMAD3 is related to biological processes such as
fibrosis. ChIP-qPCR of SMAD3 at HIF-1alpha binding sites near COL1A1 and SERPINE1
indicated that HIF-1alpha promotes the bindings of SMAD3, which is induced by TGF
beta. CONCLUSIONS: These findings suggest that HIF-1alpha induced by hypoxia
activates the TGF-beta/SMAD3 pathway. This mechanism may promote kidney injury,
especially by upregulating genes related to fibrosis.
PMID- 27607352
TI - Titanium wound chambers for wound healing research.
AB - Standardized and reproducible animal models are crucial in medical research.
Rodents are commonly used in wound healing studies since, they are easily
available, affordable and simple to handle and house. However, the most
significant limitation of rodent models is that the wounds heal by contraction
while in humans the primary mechanisms of healing are reepithelialization and
granulation tissue formation. The robust contraction results in faster wound
closure that complicates the reproducibility of rodent studies in clinical
trials. We have developed a titanium wound chamber for rodent wound healing
research. The chamber is engineered from two pieces of titanium and is placed
transcutaneously on the dorsum of a rodent. The chamber inhibits wound
contraction and provides a means for controlled monitoring and sampling of the
wound environment in vivo with minimal foreign body reaction. This technical
report introduces two modalities utilizing the titanium chambers in rats: (1)
Wound in a skin island model and, (2) Wound without skin model. Here, we
demonstrate in rats how the "wound in a skin island model" slows down wound
contraction and how the "wound without skin" model completely prevents the
closure. The titanium wound chamber provides a reproducible standardized models
for wound healing research in rodents.
PMID- 27607354
TI - Erratum.
PMID- 27607355
TI - Highly Dispersed Polyoxometalate-Doped Porous Co3 O4 Water Oxidation
Photocatalysts Derived from POM@MOF Crystalline Materials.
AB - Rational design of earth-abundant photocatalysts is an important issue for solar
energy conversion and storage. Polyoxometalate (POM)@Co3 O4 composites doped with
highly dispersive molecular metal-oxo clusters, synthesized by loading a single
Keggin-type POM cluster into each confined space of a metal-organic framework
(MOF), exhibit significantly improved photocatalytic activity in water oxidation
compared to the pure MOF-derived nanostructure. The systematic synthesis of these
composite nanocrystals allows the conditions to be tuned, and their respective
water oxidation catalytic performance can be efficiently adjusted by varying the
thermal treatment temperature and the feeding amount of the POM. This work not
only provides a modular and tunable synthetic strategy for preparing molecular
cluster@TM oxide (TM=transition metal) nanostructures, but also showcases a
universal strategy that is applicable to design and construct multifunctional
nanoporous metal oxide composite materials.
PMID- 27607353
TI - Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency.
AB - RATIONALE: Mycobacterium kansasii usually causes chronic pulmonary infections in
immunocompetent patients. In contrast, disseminated M. kansasii disease is
commonly associated with advanced human immunodeficiency virus infection, but is
reported infrequently in other immunocompromised patients. OBJECTIVES: To
identify common clinical manifestations and potential risk factors for M.
kansasii infection in patients with GATA2 deficiency. METHODS: We reviewed M.
kansasii disease associated with GATA2 deficiency at one institution and disease
associated with primary and other immunodeficiencies reported in the literature.
MEASUREMENTS AND MAIN RESULTS: Nine patients with GATA2 deficiency developed M.
kansasii infections. Six patients developed disseminated disease. All patients
presented with significant mediastinal lymphadenopathy or abscesses. Seven
patients had pulmonary risk factors, including six smokers. The majority of
patients had low numbers of neutrophils, monocytes, B cells, CD4+ T cells, and
natural killer cells. Other conditions associated with disseminated M. kansasii
disease were thymic disorders and IFN-gamma/IL-12 defects. CONCLUSIONS:
Disseminated M. kansasii disease involving mediastinal lymph nodes is
surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-gamma
synthesis and response. Disseminated M. kansasii should be considered a marker
indicating a need to evaluate for immunodeficiency syndromes.
PMID- 27607356
TI - Asymmetric Triblock Copolymer Nanocarriers for Controlled Localization and pH
Sensitive Release of Proteins.
AB - Designing nanocarriers to release proteins under specific conditions is required
to improve therapeutic approaches, especially in treating cancer and protein
deficiency diseases. We present here supramolecular assemblies based on
asymmetric poly(ethylene glycol)-b-poly(methylcaprolactone)-b-poly(2
(N,Ndiethylamino)ethyl methacrylate) (PEG-b-PMCL-b-PDMAEMA) copolymers for
controlled localization and pH-sensitive release of proteins. Copolymers self
assembled in soft nanoparticles with a core domain formed by PMCL, and a
hydrophilic domain based on PEG mainly embedded inside, and the branched PDMAEMA
exposed at the particle surface. We selected as model proteins to be attached to
the nanoparticles bovine serum albumin (BSA) and acid sphingomyelinase (ASM), the
latter being an ideal candidate for protein replacement therapy. The
hydrophilic/hydrophobic ratio, nanoparticle size, and the nature of biomolecules
are key factors for modulating protein localization and attachment efficiency.
The predominant outer shell of PDMAEMA allows efficient pH-triggered release of
BSA and ASM, and in acidic conditions >70% of the bound proteins were released.
Uptake of protein-attached nanoparticles by HELA cells, together with low
toxicity and pH-responsive release, supports such protein-bound nanoparticles as
efficient stimuli-responsive candidates for protein therapy.
PMID- 27607358
TI - Alternative splicing provides a proactive mechanism for the diurnal CONSTANS
dynamics in Arabidopsis photoperiodic flowering.
AB - The circadian clock control of CONSTANS (CO) transcription and the light-mediated
stabilization of its encoded protein coordinately adjust photoperiodic flowering
by triggering rhythmic expression of the floral integrator flowering locus T
(FT). Diurnal accumulation of CO is modulated sequentially by distinct E3
ubiquitin ligases, allowing peak CO to occur in the late afternoon under long
days. Here we show that CO abundance is not simply targeted by E3 enzymes but is
also actively self-adjusted through dynamic interactions between two CO isoforms.
Alternative splicing of CO produces two protein variants, the full-size COalpha
and the truncated CObeta lacking DNA-binding affinity. Notably, CObeta, which is
resistant to E3 enzymes, induces the interaction of COalpha with CO-destabilizing
E3 enzymes but inhibits the association of COalpha with CO-stabilizing E3 ligase.
These observations demonstrate that CO plays an active role in sustaining its
diurnal accumulation dynamics during Arabidopsis photoperiodic flowering.
PMID- 27607357
TI - Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial
Pathogen with a Large Pan-Genome.
AB - The interaction between an antibiotic and bacterium is not merely restricted to
the drug and its direct target, rather antibiotic induced stress seems to
resonate through the bacterium, creating selective pressures that drive the
emergence of adaptive mutations not only in the direct target, but in genes
involved in many different fundamental processes as well. Surprisingly, it has
been shown that adaptive mutations do not necessarily have the same effect in all
species, indicating that the genetic background influences how phenotypes are
manifested. However, to what extent the genetic background affects the manner in
which a bacterium experiences antibiotic stress, and how this stress is processed
is unclear. Here we employ the genome-wide tool Tn-Seq to construct daptomycin
sensitivity profiles for two strains of the bacterial pathogen Streptococcus
pneumoniae. Remarkably, over half of the genes that are important for dealing
with antibiotic-induced stress in one strain are dispensable in another. By
confirming over 100 genotype-phenotype relationships, probing potassium-loss,
employing genetic interaction mapping as well as temporal gene-expression
experiments we reveal genome-wide conditionally important/essential genes, we
discover roles for genes with unknown function, and uncover parts of the
antibiotic's mode-of-action. Moreover, by mapping the underlying genomic network
for two query genes we encounter little conservation in network connectivity
between strains as well as profound differences in regulatory relationships. Our
approach uniquely enables genome-wide fitness comparisons across strains,
facilitating the discovery that antibiotic responses are complex events that can
vary widely between strains, which suggests that in some cases the emergence of
resistance could be strain specific and at least for species with a large pan
genome less predictable.
PMID- 27607359
TI - Affective temperaments and emotional traits are associated with a positive
screening for premenstrual dysphoric disorder.
AB - OBJECTIVES: Preliminary evidence indicates that premenstrual dysphoric disorder
(PMDD) may be frequently co-morbid with bipolar spectrum disorders. In addition,
the manifestations of PMDD seem similar to a subthreshold depressive mixed state.
Nevertheless, the associations between PMDD and affective temperaments and
emotional traits have not been previously investigated. METHODS: A consecutive
sample of 514 drug-free Brazilian women (mean age: 22.8; SD=5.4years) took part
in this cross-sectional study. Screening for PMDD was obtained with the validated
Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST).
Affective temperaments and emotional dimensions were evaluated with the Affective
and Emotional Composite Temperament Scale (AFECTS). In addition, socio
demographic and data on menstrual cycle were collected. RESULTS: According to the
PSST, 83 (16.1%) women screened positive for PMDD, while 216 (42.0%) women had
no/mild premenstrual symptoms. The cyclothymic temperament was independently
associated with PMDD (OR=4.57; 95% CI: 2.11-9.90), while the euthymic temperament
had an independent association with a lower likelihood of a positive screening
for PMDD (OR=0.28; 95% CI: 0.12-0.64). In addition, anger and sensitivity emerged
as emotional dimensions significantly associated with PMDD. CONCLUSIONS: A
positive screening for PMDD was associated with a predominant cyclothymic
temperament, while an euthymic temperament was associated with a lower likelihood
for a positive screening for PMDD. These data deserve replication in prospective
studies.
PMID- 27607361
TI - Empirical exploration of brilliance in health care: perceptions of health
professionals.
AB - Objective The aim of the present study was to develop a positive organisational
scholarship in health care approach to health management, informed by health
managers and health professionals' experiences of brilliance in health care
delivery. Methods A sample of postgraduate students with professional and/or
management experience within a health service was invited to share their
experiences of brilliant health services via online discussions and a survey
running on the SurveyMonkey platform. A lexical analysis of student contributions
was conducted using the individual as the unit of analysis. Results Using lexical
analysis, the examination of themes in the concept map, the relationships between
themes and the relationships between concepts identified 'care' as the most
important concept in recognising brilliance in health care, followed by the
concepts of 'staff' and 'patient'. Conclusions The research presents empirical
material to support the emergence of an evidence-based health professional
perspective of brilliance in health management. The findings support other
studies that have drawn on both quantitative and qualitative materials to explore
brilliance in health care. Pockets of brilliance have been previously identified
as catalysts for changing health care systems. Both quality, seen as driven from
the outside, and excellence, driven from within individuals, are necessary to
produce brilliance. What is known about the topic? The quest for brilliance in
health care is not easy but essential to reinvigorating and energising health
professionals to pursue the highest possible standards of health care delivery.
What does this paper add? Using an innovative methodology, the present study
identified the key drivers that health care professionals believe are vital to
moving in the direction of identifying brilliant performance. What are the
implications for practitioners? This work presents evidence on the perceptions of
leadership and management practices associated with brilliant health management.
Lessons learned from exceptionally well-delivered services contain different
templates for change than those dealing with failures, errors, misconduct and the
resulting negativity.
PMID- 27607360
TI - The Global Economic and Health Burden of Human Hookworm Infection.
AB - BACKGROUND: Even though human hookworm infection is highly endemic in many
countries throughout the world, its global economic and health impact is not well
known. Without a better understanding of hookworm's economic burden worldwide, it
is difficult for decision makers such as funders, policy makers, disease control
officials, and intervention manufacturers to determine how much time, energy, and
resources to invest in hookworm control. METHODOLOGY/PRINCIPLE FINDINGS: We
developed a computational simulation model to estimate the economic and health
burden of hookworm infection in every country, WHO region, and globally, in 2016
from the societal perspective. Globally, hookworm infection resulted in a total
2,126,280 DALYs using 2004 disability weight estimates and 4,087,803 DALYs using
2010 disability weight estimates (excluding cognitive impairment outcomes).
Including cognitive impairment did not significantly increase DALYs worldwide.
Total productivity losses varied with the probability of anemia and calculation
method used, ranging from $7.5 billion to $138.9 billion annually using gross
national income per capita as a proxy for annual wages and ranging from $2.5
billion to $43.9 billion using minimum wage as a proxy for annual wages.
CONCLUSION: Even though hookworm is classified as a neglected tropical disease,
its economic and health burden exceeded published estimates for a number of
diseases that have received comparatively more attention than hookworm such as
rotavirus. Additionally, certain large countries that are transitioning to higher
income countries such as Brazil and China, still face considerable hookworm
burden.
PMID- 27607362
TI - Bone mineral density is reduced by telmisartan in male spontaneously hypertensive
rats.
AB - BACKGROUND: Telmisartan, an angiotensin AT1 receptor blocker, and treadmill
running were compared for their effects on bone mineral density (BMD) and
biomechanical properties of male spontaneously hypertensive rats (SHR). It was
hypothesized that running (18m/min/60min/d) and telmisartan (5mg/kg/d) would have
a positive effect on bone parameters. METHODS: Three-month-old male SHRs were
divided into three groups: sedentary (S), telmisartan (T), and exercise (E). At
the end of an 8-week protocol, femur and lumbar vertebrae were analyzed by dual
energy X-ray absorptiometry (DXA) for bone mineral density and by the three-point
bending test for biomechanical properties. Blood pressure in all groups was
measured by a tail-cuff manometer. RESULTS: Telmisartan and treadmill running
reduced blood pressure when compared to the sedentary group; however, telmisartan
did not improve bone characteristics. Instead, it reduced BMD of femur total and
lumbar vertebrae and worsened bone biomechanic properties. Treadmill running
maintained bone characteristics and hence was effective in maintaining bone
health. CONCLUSION: Results showed that telmisartan negatively affected bones
suggesting that caution should be taken in possible therapeutic applications for
protecting bone health in hypertensive conditions. More studies are necessary to
clarify the mechanisms through which telmisartan favors bone loss in this model.
PMID- 27607363
TI - Use of low-dose tacrolimus and associated hypomagnesemia in the prevention of
erectile dysfunction following prostatectomy for prostate cancer.
AB - BACKGROUND: Hypomagnesemia with urinary magnesium wasting is a well described
adverse event with calcineurin inhibitor therapy. Prostate cancer is the most
prevalent cancer in men in the United States. Injury to the cavernous nerves
during radical prostatectomy frequently results in erectile dysfunction.
Tacrolimus has been shown to be neuroprotective in the rat cavernous nerve injury
model, an animal model representative of the neural injury that occurs in humans
at the time of radical prostatectomy. METHODS: In a randomized, double-blind,
placebo-controlled trial, the utility of tacrolimus was assessed for prevention
of erectile dysfunction following bilateral nerve-sparing radical prostatectomy.
RESULTS: Low dose tacrolimus, associated with low trough levels, resulted in mild
hypomagnesemia, which was an early and persistent finding. As early as one week
after institution of therapy, mean and median serum magnesium levels were
significantly lower in the tacrolimus arm as compared to the placebo arm (p<0.001
for both). While the mean and median levels were within the normal range at Week
1, 10.9% of tacrolimus-treated patients had levels <1.8mg/dL, compared to none in
the placebo arm (p=0.017). Median and mean levels remained significantly
different at Week 5, Month 3 and Month 6. No clinical manifestations of
hypomagnesemia were noted and no subject required treatment with magnesium.
Changes in serum magnesium occurred earlier than other potential metabolic
adverse events described with tacrolimus (changes in serum glucose, creatinine or
potassium). CONCLUSIONS: These data indicate that mild hypomagnesemia is an early
and sensitive biomarker for the effect of tacrolimus on the kidney.
PMID- 27607364
TI - Translocator protein (TSPO) ligands for the diagnosis or treatment of
neurodegenerative diseases: a patent review (2010-2015; part 1).
AB - INTRODUCTION: The translocator protein (TSPO) is an emerging target in diverse
neurodegenerative diseases. Up-regulated TSPO in the central nervous system (CNS)
appears to be involved in neuroinflammatory processes; therefore, the development
of potent TSPO ligands is a promising method for alleviating or imaging patients
with neurodegenerative diseases. Areas covered: This review will provide an
overview of recently developed TSPO ligands patented from 2010 to 2015. Part 1
will present a summary focusing on TSPO ligands other than indole-based or
cholesterol-like compounds, which will be discussed in part 2. Part 1 covers
diverse benzodiazepine-derived analogues such as isoquinoline carboxamides and
aryloxyanilides. Moreover, bicyclic ring structures such as imidazopyridine,
pyrazolopyrimidine, and phenylpurine will be highlighted as promising scaffolds
for TSPO ligands. A brief analysis of currently reported TSPO structures will
also be covered in part 1. Expert opinion: Although the underlying
pharmacological mechanism of TSPO remains to be elucidated, several TSPO ligands
have shown therapeutic efficacy in experimental animal models of
neurodegenerative diseases. In addition, radioactive TSPO ligands have been
extensively studied for the diagnosis of neurodegenerative processes. Thus,
further studies on both the basic and applied mechanisms of TSPO are warranted in
the pursuit of successful pharmacological applications of TSPO ligands.
PMID- 27607404
TI - Epidural Management by Nonanesthesiologists: Is This an Example of Poor Care
Coordination?
PMID- 27607402
TI - Production of Pure Aqueous 13 C-Hyperpolarized Acetate by Heterogeneous
Parahydrogen-Induced Polarization.
AB - A supported metal catalyst was designed, characterized, and tested for aqueous
phase heterogeneous hydrogenation of vinyl acetate with parahydrogen to produce
13 C-hyperpolarized ethyl acetate for potential biomedical applications. The
Rh/TiO2 catalyst with a metal loading of 23.2 wt % produced strongly
hyperpolarized 13 C-enriched ethyl acetate-1-13 C detected at 9.4 T. An
approximately 14-fold 13 C signal enhancement was detected using circa 50 %
parahydrogen gas without taking into account relaxation losses before and after
polarization transfer by magnetic field cycling from nascent parahydrogen-derived
protons to 13 C nuclei. This first observation of 13 C PHIP-hyperpolarized
products over a supported metal catalyst in an aqueous medium opens up new
possibilities for production of catalyst-free aqueous solutions of nontoxic
hyperpolarized contrast agents for a wide range of biomolecules amenable to the
parahydrogen induced polarization by side arm hydrogenation (PHIP-SAH) approach.
PMID- 27607403
TI - The Relationship Between Preoperative Clinical Presentation and Quantitative
Magnetic Resonance Imaging Features in Patients With Degenerative Cervical
Myelopathy.
AB - BACKGROUND: Degenerative cervical myelopathy encompasses a group of conditions
resulting in progressive spinal cord injury through static and dynamic
compression. Although a constellation of changes can present on magnetic
resonance imaging (MRI), the clinical significance of these findings remains a
subject of controversy and discussion. OBJECTIVE: To investigate the relationship
between clinical presentation and quantitative MRI features in patients with
degenerative cervical myelopathy. METHODS: A secondary analysis of MRI and
clinical data from 114 patients enrolled in a prospective, multicenter study was
conducted. MRIs were assessed for maximum spinal cord compression (MSCC), maximum
canal compromise (MCC), signal changes, and a signal change ratio (SCR). MRI
features were compared between patients with and those without myelopathy
symptoms with the use of t tests. Correlations between MRI features and duration
of symptoms were assessed with the Spearman rho. RESULTS: Numb hands and Hoffmann
sign were associated with greater MSCC ( P < .05); broad-based, unstable gait,
impairment of gait, and Hoffmann sign were associated with greater MCC ( P <
.05); and numb hands, Hoffmann sign, Babinski sign, lower limb spasticity,
hyperreflexia, and T1 hypointensity were associated with greater SCR ( P < .05).
Patients with a T2 signal hyperintensity had greater MSCC and MCC ( P < .001).
CONCLUSION: MSCC was associated with upper limb manifestations, and SCR was
associated with upper limb, lower limb, and general neurological deficits.
Hoffmann sign occurred more commonly in patients with a greater MSCC, MCC and
SCR. The Lhermitte phenomenon presented more commonly in patients with a lower
SCR and may be an early indicator of mild spinal cord involvement. Research to
validate these findings is required.
PMID- 27607405
TI - A Case Report of the Anesthetic Management for Liver Retransplantation in a
Patient With a Bronchobiliary Fistula.
AB - A 64-year-old woman with a previous liver transplant developed graft failure with
biliary complications including a bronchobiliary fistula, which did not respond
to preoperative conservative therapy. Liver retransplantation provided definitive
therapy for the liver failure and bronchobiliary fistula. We present anesthestic
considerations for the intraoperative management of a liver retransplant with one
lung ventilation.
PMID- 27607406
TI - Extracorporeal Membrane Oxygenation for Treatment of Acute Inverted Takotsubo
Like Cardiomyopathy From Hemorrhagic Pheochromocytoma in Late Pregnancy.
AB - We describe the first case of a pregnant woman presenting with an acute inverted
takotsubo-like cardiomyopathy caused by a postpartum diagnosed hemorrhagic
pheochromocytoma, successfully treated with percutaneous venoarterial
extracorporeal membrane oxygenation (va-ECMO). During admission, an emergency
cesarean delivery had to be performed. The fetus needed resuscitation for 5
minutes. The mother was successfully resuscitated and treated with percutaneous
va-ECMO for 7 days. Despite advances in diagnostic techniques during the past
decade, in many cases, pheochromocytoma in pregnancy is still missed. This
results in a maternal and fetal mortality rate of up to 30% in both.
PMID- 27607407
TI - Ultrasound-Guided Temporomandibular Joint Injection for Chronic
Posthemimandibulectomy Jaw Pain.
AB - Temporomandibular joint (TMJ) pain can be difficult to diagnose and treat. We
describe a patient with left jaw pain after right hemimandibulectomy. The patient
was initially managed conservatively, which failed to reduce pain. He was then
administered inferior alveolar nerve block and TMJ injection with steroid and
local anesthetic. These injections provided temporary pain relief that lasted
approximately 1 month and the pain recurred. Computed tomography scan showed
lateral displacement of left mandibular condyle. He was then given ultrasound
guided TMJ injection of steroid and local anesthetic. This injection provided
lasting pain relief.
PMID- 27607408
TI - Impaired Ventilation and Oxygenation After Emergency Cricothyrotomy:
Recommendations for the Management of Suboptimal Invasive Airway Access.
AB - Invasive airway access by emergent cricothyrotomy remains an essential treatment
modality in "can't intubate/can't ventilate" scenarios. Although numerous
commercial devices are available, limited comparative data exist with regard to
the ventilation and oxygenation parameters of these devices. We report a case of
severely compromised respiratory function while using the Quicktrach II, a
commercially available emergency cricothyrotomy device. Because of oxygenation
and ventilatory insufficiency, our patient required emergent removal of the
device and surgical tracheostomy to improve respiratory function. When confronted
with a difficult airway, anesthesiologists and surgeons should be aware of
commonly encountered cricothyrotomy devices and their potential limitations.
PMID- 27607409
TI - Biological activity of Myrtaceae plant essential oils and their major components
against Drosophila suzukii (Diptera: Drosophilidae).
AB - BACKGROUND: The spotted-wing drosophila (SWD), Drosophila suzukii (Matsumura), is
a globally invasive and serious pest of numerous soft-skinned fruit crops.
Assessments were made of fumigant and contact toxicities of 12 Myrtaceae plant
essential oils (EOs) and their components. For determining the mode of action of
major components of active EOs, their activities against acetylcholinesterase
(AChE) and Glutathione S-transferase (GST) were also assessed. RESULTS: Strong
fumigant and contact toxicities were observed from EOs of Eucalyptus citriodora
and Melaleuca teretifolia. The main components of E. citriodora were citronellal
and isopulegol, whereas those of M. teretifolia were neral and geranial. Geranial
showed the strongest fumigant activity, followed by citronellal or neral, M.
teretifolia EO, isopulegol and E. citriodora EO. In contact toxicity assays,
geranial also exhibited the strongest insecticidal activity, followed by neral or
M. teretifolia EO, citronellol, citronellal, isopulegol and E. citriodora EO.
Among the major components, all compounds showed low AChE inhibitory activity,
while neral and geranial showed GST inhibitory activity against SWD. CONCLUSION:
Myrtaceae plant EOs and their components have an excellent potential for being
used in the control of SWD adults and could be useful in the development of more
effective natural compounds as alternatives to synthetic pesticides. (c) 2016
Society of Chemical Industry.
PMID- 27607410
TI - Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal
Administration to the Ewe.
AB - Opioids given to pregnant and parturient women are relatively freely transferred
across the placenta. Spinal, epidural and intravenous fentanyl has been studied
in pregnant women and neonates, but foetal safety of fentanyl dosing with
transdermal patch during pregnancy and labour is not sufficiently studied. Foetal
pH is physiologically lower than maternal pH, and thus, opioids, which are weak
bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen
acidosis, and ion trapping induced by low pH is assumed to increase the foetal
exposure to opioids. Here, we show that no correlation between foetal acidosis
and ion trapping of fentanyl could be found. In three experiments, 29 pregnant
sheep were administered fentanyl with 2 MUg/kg/h patch supplemented with IV
boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml
(quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and
median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during
the first hours after the fentanyl administration. Low foetal pH and pH
difference between ewe and the foetus did not correlate with fentanyl
concentration in the foetus or F/M ratio. At steady-state during the second patch
worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was
0.69. Our results demonstrate that drug accumulation to foetus caused by ion
trapping seen with some weak base opioids may not be that significant with
fentanyl. These results have a clinical relevance when fentanyl is dosed to
pregnant woman and the foetus is acidemic.
PMID- 27607411
TI - Early treatment intensification induces favourable radiographic outcomes
according to predicted versus observed radiographic progression in early
rheumatoid arthritis: a subanalysis of the randomised FIN-RACo and NEO-RACo
trials.
AB - OBJECTIVES: Predicted versus observed radiographic progression in early
rheumatoid arthritis (POPeRA) was applied to demonstrate how various treatment
modalities affect and potentially minimise radiographic progression over time.
METHODS: The POPeRA method utilises the baseline radiographic score and patient
reported symptom duration to predict radiographic outcomes. It was applied at
baseline, 2, and 5 years to patients with eRA from the randomised Finnish RA
Combination trial (FIN-RACo) (n=144) and New Finnish RA Combination Therapy (NEO
RACo) (n=90) trials. For FIN-RACo, patients were randomised either to a single
DMARD (sulfasalazine, with or without prednisolone) or to combination therapy
(methotrexate+sulfasalazine+hydroxychloroquine, i.e. triple therapy, with
prednisolone). In NEO-RACo, all patients were assigned intensified combination
therapy (including 7.5 mg prednisolone/day) plus a randomised 6-month induction
of either placebo or anti-TNF treatment (infliximab). RESULTS: In FIN-RACo,
combination versus monotherapy resulted in superior outcomes in the change from
predicted progression over 2 and 5 years (mean 35.7% reduction vs. -32.9%, a
worsening from predicted, p=0.001; 34.2% vs. -17.8%, p=0.003, respectively). In
NEO-RACo, combination+anti-TNF induction led to significantly greater reductions
from predicted progression than combination+placebo, both at 2 and 5 years of
follow-up (98.5% vs. 83.4%, p=0.005; 92.4% vs. 82.5%, p=0.027, respectively).
Importantly, anti-TNF add-on led to superior reductions from predicted among RF
positive patients (2 years: 97.4% vs. 80.4%, p=0.009; 5 years: 90.2% vs. 80.1%,
p=0.030), but not among RF-negative patients. CONCLUSIONS: These results confirm
that conventional combination therapy in eRA has a long-term radiographic benefit
versus monotherapy. Through POPeRA, it was made evident that anti-TNF induction
therapy for 6 months further increases the long-term radiographic benefit of
combination therapy in RF-positive patients.
PMID- 27607412
TI - Usefulness of real-time tissue elastography for detecting the border of basal
cell carcinomas.
AB - Preoperative evaluation of tumor thickness and silhouette in basal cell carcinoma
(BCC) is one of the important assessments to be done. However, evaluation is not
always sufficient even utilizing sonography and magnetic resonance imaging.
Recently, a new technique called real-time tissue elastography (RTE) was
developed that can display the hardness of tissue as a color overlay of a
sonographic image. Therefore, RTE could be used as a tool for detecting the tumor
border according to differences in tissue rigidity. In the present study, the
correlation between histopathological and RTE tumor thickness measurements was
evaluated for BCC. Eleven BCC (six nodular, three superficial, and two adenoid or
cystic) from individual patients were evaluated. Tumor silhouette and thickness
were detected using conventional B-mode sonography and RTE. All lesions were
surgically excised and tumor thickness was also examined histologically. In the
six nodular BCC, the tumor silhouette determined by RTE showed a close
correlation with the results of histopathology. Particularly, for four out of the
six cases, the correlation was excellent. In addition, the mean difference in
tumor thickness measurements between histology and RTE (-0.368 mm) was lower than
that between histology and B-mode sonography (-0.835 mm). As for the superficial
BCC, tumor thickness was too thin to evaluate. Tumor thickness measured by B-mode
sonography and RTE was identical for two cases of adenoid or cystic BCC. In
conclusion, RTE is useful in the preoperative assessment of tumor thickness,
especially with the nodular type of BCC, and allows us to determine adequate
surgical margins.
PMID- 27607413
TI - Alleviating Maneuvers for Benign Essential Blepharospasm and Hemifacial Spasm.
PMID- 27607414
TI - In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft
Versus-Host Disease.
AB - PURPOSE: To compare densities of corneal epithelial dendritic cells (DCs),
corneal subbasal nerves, and conjunctival epithelial immune cells (EICs) between
patients with dry eye disease (DED) with and without graft-versus-host disease
(GVHD) using in vivo confocal microscopy (IVCM). METHODS: This study included 54
patients who had moderate to severe DED either associated with (n = 33) or
without (n = 21) chronic GVHD. In addition to evaluating clinical parameters of
DED, images obtained by laser-scanning IVCM of the central cornea and superior
tarsal conjunctiva were analyzed to measure densities of corneal epithelial DCs,
corneal subbasal nerves, and conjunctival EICs. RESULTS: Although there were no
significant differences between GVHD and non-GVHD groups in symptom scores, the
GVHD group had significantly worse corneal fluorescein staining, tear break-up
time, and Schirmer's scores than the non-GVHD group. Corneal epithelial DC
density, corneal subbasal nerve density, and conjunctival EIC density were 148 +/
135 cells/mm2, 16.3 +/- 6.1 mm/mm2, and 670 +/- 267 cells/mm2, respectively, in
the GVHD group; and 122 +/- 99 cells/mm2, 18.3 +/- 5.1 mm/mm2, and 572 +/- 271
cells/mm2, respectively, in the non-GVHD group. After adjusting for clinical
parameters, including the DED severity, none of the IVCM parameters was
significantly different between the GVHD versus non-GVHD groups (P = 0.82, P =
0.21, and P = 0.60, respectively). CONCLUSIONS: In GVHD-associated DED, cellular
changes in the cornea and conjunctiva observed by IVCM were similar to those seen
in patients who have non-GVHD dry eye with the same level of disease severity.
Therefore, corneal and conjunctival IVCM findings in GVHD-associated DED are
possibly reflective of the local disease (DED) severity rather than the
underlying systemic disease process.
PMID- 27607415
TI - Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and
Retinal Ganglion Cells Under Taurine Depletion.
AB - PURPOSE: Taurine depletion is known to induce photoreceptor degeneration and was
recently found to also trigger retinal ganglion cell (RGC) loss similar to the
retinal toxicity of vigabatrin. Our objective was to study the topographical loss
of RGCs and cone photoreceptors, with a distinction between the two cone types (S
and L- cones) in an animal model of induced taurine depletion. METHODS: We used
the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to
induce taurine depletion at a concentration of 1% in the drinking water. Spectral
domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were
performed on animals after 2 months of GES treatment administered through the
drinking water. Retinas were dissected as wholemounts and immunodetection of
Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number
of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their
retinal distribution studied using isodensity maps. RESULTS: The treatment
resulted in a significant reduction in plasma taurine levels and a profound
dysfunction of visual performance as shown by ERG recordings. Optical coherence
tomography analysis revealed that the retina was thinner in the taurine-depleted
group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with
greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly
distributed. CONCLUSIONS: This study confirms that taurine depletion causes RGC
and cone loss. Electroretinograms results show that taurine depletion induces
retinal dysfunction in photoreceptors and in the inner retina. It establishes a
gradient of cell loss depending on the cell type from S-opsin+cones, L
opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S
cone population may underline different cellular mechanisms of cellular
degeneration and suggests that S-cones may be more sensitive to light-induced
retinal toxicity enhanced by the taurine depletion.
PMID- 27607417
TI - Fine Motor Skills of Children With Amblyopia Improve Following Binocular
Treatment.
AB - PURPOSE: The purpose of this study was to determine whether reduced fine motor
skills in children with amblyopia improve after binocular treatment and whether
improvements are sustained once treatment has ceased. METHODS: Fine motor skills
(FMS [Bruininks-Oseretsky Test of Motor Proficiency]), visual acuity (VA [Early
Treatment of Diabetic Retinopathy Study chart]) and level of binocular function
(BF [Randot preschool stereoacuity and Worth 4 Dot]) were measured in children
with amblyopia (n = 20; age: 8.5 +/- 1.3 years; 11 anisometropic; 5 strabismic; 4
mixed) and in a group of visually normal children (n = 10; age: 9.63 +/- 1.6
years). Eighteen children with amblyopia subsequently completed 5 weeks of
binocular treatment provided by home-based dichoptic iPod game play. FMS, VA, and
BF were retested at the end of treatment and 12 weeks after treatment cessation.
All visually normal children also completed FMS measurements at baseline and 5
weeks later to assess test-retest variability of the FMS scores. RESULTS: Prior
to treatment, FMS scores in children with amblyopia were poorer than those in
children with normal vision (P < 0.05). In the children with amblyopia, binocular
treatment significantly improved FMS scores (P < 0.05). Better baseline amblyopic
eye VA and BF were associated with greater improvements in FMS score.
Improvements were still evident at 12 weeks post treatment. In the visually
normal children, FMS scores remained stable across the two test sessions.
CONCLUSIONS: Binocular treatment provided by dichoptic iPod game play improved
FMS performance in children with amblyopia, particularly in those with less
severe amblyopia. Improvements were maintained at 3 months following cessation of
treatment.
PMID- 27607416
TI - Oxidized Lipoprotein Uptake Through the CD36 Receptor Activates the NLRP3
Inflammasome in Human Retinal Pigment Epithelial Cells.
AB - PURPOSE: Accumulation of oxidized phospholipids/lipoproteins with age is
suggested to contribute to the pathogenesis of AMD. We investigated the effect of
oxidized LDL (ox-LDL) on human RPE cells. METHODS: Primary human fetal RPE (hf
RPE) and ARPE-19 cells were treated with different doses of LDL or ox-LDL.
Assessment of cell death was measured by lactate dehydrogenase release into the
conditioned media. Barrier function of RPE was assayed by measuring
transepithelial resistance. Lysosomal accumulation of ox-LDL was determined by
immunostaining. Expression of CD36 was determined by RT-PCR; protein blot and
function was examined by receptor blocking. NLRP3 inflammasome activation was
assessed by RT-PCR, protein blot, caspase-1 fluorescent probe assay, and
inhibitor assays. RESULTS: Treatment with ox-LDL, but not LDL, for 48 hours
caused significant increase in hf-RPE and ARPE-19 (P < 0.001) cell death.
Oxidized LDL treatment of hf-RPE cells resulted in a significant decrease in
transepithelial resistance (P < 0.001 at 24 hours and P < 0.01 at 48 hours)
relative to LDL-treated and control cells. Internalized ox-LDL was targeted to
RPE lysosomes. Uptake of ox-LDL but not LDL significantly increased CD36 protein
and mRNA levels by more than 2-fold. Reverse transcription PCR, protein blot, and
caspase-1 fluorescent probe assay revealed that ox-LDL treatment induced NLRP3
inflammasome when compared with LDL treatment and control. Inhibition of NLRP3
activation using 10 MUM isoliquiritigenin significantly (P < 0.001) inhibited ox
LDL induced cytotoxicity. CONCLUSIONS: These data are consistent with the concept
that ox-LDL play a role in the pathogenesis of AMD by NLRP3 inflammasome
activation. Suppression of NLRP3 inflammasome activation could attenuate RPE
degeneration and AMD progression.
PMID- 27607418
TI - Relationship Between the Altered Expression and Epigenetics of GSTM3 and Age
Related Cataract.
AB - PURPOSE: Glutathione S-Transferase Mu 3 (GSTM3) protects the lens from oxidative
stress that contributes to age-related cataract (ARC) formation. We examined the
expression and epigenetics of GSTM3 in lens epithelial cells (LECs) and lens
cortex of ARC, and investigated the potential role of molecular changes in ARC
pathogenesis. METHODS: This study included 120 ARCs and 40 controls. Expression
of GSTM3, DNA methylation, and histone modification were assessed by
quantificational real-time PCR, Western blot, bisulfite-sequencing PCR,
pyrosequencing, and chromatin immunoprecipitation assay. Human lens epithelial
(HLE) cell lines, SRA01/04 and HLEB3, were served as an in vitro model to observe
the relationship between epigenetic status and GSTM3 expression. Potential
transcription factors binding to GSTM3 promoter were detected by electrophoretic
mobility shift assay. RESULTS: Expression of GSTM3 decreased in ARC lens tissues
compared to that in the controls, which correlated with the hypermethylation of
GSTM3 promoter. Lower level of GSTM3 was detected in HLEB3 than in SRA01/04,
while HLEB3 displayed hypermethylation of GSTM3 and SRA01/04 did not. Compared to
SRA01/04, HLEB3 displayed lower acetylated H3 and higher trimethylated H3K9
levels. After treatment with DNA methyltransferase inhibitor or histone
deacetylase inhibitor, HLEB3 had an increased GSTM3 expression. Methylation of
GSTM3 promoter abrogated the potential transcription factor binding. The GSTM3
expression declined in hydrogen peroxide-treated HLE cell lines. CONCLUSIONS:
Expression of GSTM3 might be regulated by epigenetic changes in lens tissue.
Hypermethylation in GSTM3 promoter and altered histone modification might have a
role in the ARC formation. The results provided a potential strategy of ARC
management by manipulating epigenetic changes.
PMID- 27607419
TI - Influence of Exercise on Intraocular Pressure, Schlemm's Canal, and the
Trabecular Meshwork.
AB - PURPOSE: We aimed to assess the changes in IOP, Schlemm's canal (SC), and the
trabecular meshwork (TM) in healthy individuals after exercise. METHODS: The area
and perimeter of SC, TM thickness, IOP, pupil diameter, blood pressure (BP),
heart rate, and plasma catecholamine concentrations were measured in 29 young
healthy individuals before and after exercise by jogging for 20 minutes. The TM
and SC in the superior, inferior, nasal, and temporal regions were evaluated by
80-MHz ultrasound biomicroscopy. RESULTS: In comparison with the baseline values,
the post-exercise values of IOP had significantly reduced, and those of the pupil
diameter, systolic and diastolic BP, and plasma catecholamine concentrations had
significantly increased (all, P < 0.05). There were no significant differences in
the proportions of eyes with observable SC before (81.9%) and after (90.5%; X =
3.652; P = 0.057) exercise. In comparison with the baseline values, the mean
values of area (132.83 +/- 19.67 vs. 155.33 +/- 21.46 pixels; P < 0.001) and
perimeter (54.94 +/- 4.95 vs. 60.23 +/- 4.19 pixels; P < 0.001) of SC and TM
thickness (10.30 +/- 1.28 vs. 11.48 +/- 1.07 pixels; P < 0.001) after exercise
were increased. The increase in area (r = 0.019, P = 0.923) and perimeter (r =
0.109, P = 0.573) of SC and TM thickness (r = -0.088, P = 0.651) were not
significantly correlated with the decrease in IOP. CONCLUSIONS: Aerobic exercise
could cause sympathetic nerve stimulation, consequently causing the expansion of
the TM and SC, which, in turn, leads to IOP reduction. Furthermore, SC and the TM
might have an autonomic regulation function, and their expansion and collapse
might not be completely dependent on the IOP.
PMID- 27607420
TI - Tetramethylpyrazine Attenuates Transdifferentiation of TGF-beta2-Treated Human
Tenon's Fibroblasts.
AB - PURPOSE: To investigate the pharmacologic effect of tetramethylpyrazine (TMP) on
human Tenon's fibroblasts (HTFs), the cells implicated in scarring after
filtration surgery. METHODS: Transforming growth factor-beta2 (TGF-beta2) was
used to stimulate a fibrotic phenotype in primary HTFs, and the influence of TMP
on the fibrotic phenotype was assessed. Cell proliferation and cell cycle
regulation were profiled. Immunofluorescence staining tracked proliferating cell
nuclear antigen (PCNA) expression. Transwell assays monitored cell migration.
Flow cytometry measured TMP toxicity. In addition, in TGF-beta2-treated HTFs,
Western blot and immunofluorescence were employed to assess the expression of
alpha-smooth muscle actin (alpha-SMA). The TMP-mediated activity on cytoskeletal
arrangements and extracellular matrix (ECM) accumulation in HTFs was evaluated
using actin polymerization and Western blot assays. Moreover, TGF-beta-dependent
activation of Smad3 and p38 was examined by Western blot analysis. RESULTS: In
TGF-beta2-treated HTFs, TMP reduced proliferation and migration but did not
induce apoptosis. Moreover, TMP attenuated expression of alpha-SMA and suppressed
stress fiber formation stimulated by profibrotic cytokine; it also counteracted
TGF-beta2-induced cytoskeletal rearrangements, morphologic changes, and ECM
accumulation. Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling
were downstream of the TMP-sensitive effect. CONCLUSIONS: Tetramethylpyrazine
counteracts TGF-beta2-mediated myofibroblast transdifferentiation and attenuates
ECM component deposition and cell proliferation in HTFs, implicating TMP as a
potential antifibrosis agent in glaucoma filtration surgery.
PMID- 27607421
TI - Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human
Corneal Endothelial Cells.
AB - PURPOSE: To identify the subpopulation (SP) among heterogeneous cultured human
corneal endothelial cells (cHCECs) devoid of cell-state transition applicable for
cell-based therapy. METHODS: Subpopulation presence in cHCECs was confirmed via
surface CD-marker expression level by flow cytometry. CD markers effective for
distinguishing distinct SPs were selected by analyzing those on established
cHCECs with a small cell area and high cell density. Contrasting features among
three typical cHCEC SPs was confirmed by PCR array for extracellular matrix
(ECM). Combined analysis of CD markers was performed to identify the SP (effector
cells) applicable for therapy. ZO-1 and Na+/K+ ATPase, CD200, and HLA expression
were compared among heterogeneous SPs. RESULTS: Flow cytometry analysis
identified the effector cell expressing CD166+CD105-CD44-~+/-CD26-CD24-, but
CD200-, and the presence of other SPs with CD166+ CD105-CD44+++ (CD26 and CD24,
either + or -) was confirmed. PCR array revealed three distinct ECM expression
profiles. Some SPs expressed ZO-1 and Na+/K+ ATPase at comparable levels with
effector cells, while only one SP expressed CD200, but not on effector cells.
Human leukocyte antigen expression was most reduced in the effector SP. The
proportion of effector cells (E-ratio) inversely paralleled donor age and
decreased during prolonged culture passages. The presence of Rho-associated
protein kinase (ROCK) inhibitor increased the E-ratio in cHCECs. The average area
of effector cells was approximately 200~220 MUm2, and the density of cHCECs
exceeded 2500 cells/mm2. CONCLUSIONS: A specified cultured effector cell
population sharing the surface phenotypes with mature HCECs in corneal tissues
may serve as an alternative to donor corneas for the treatment of corneal
endothelial dysfunction.
PMID- 27607422
TI - Role of Dicer Enzyme in the Regulation of Store Operated Calcium Entry (SOCE) in
CD4+ T Cells.
AB - BACKGROUND/AIMS: Activation of T cell receptors (TCRs) in CD4+ T cells leads to a
cascade of signalling reactions including increase of intracellular calcium
(Ca2+) levels with subsequent Ca2+ dependent stimulation of gene expression,
proliferation, cell motility and cytokine release. The increase of cytosolic Ca2+
results from intracellular Ca2+ release with subsequent activation of store
operated Ca2+ entry (SOCE). Previous studies suggested miRNAs are required for
the development and functions of CD4+ T cells. An enzyme called Dicer is required
during the process of manufacturing mature miRNAs from the precursor miRNAs. In
this study, we explored whether loss of Dicer in CD4+ T cells affects SOCE and
thus Ca2+ dependent regulation of cellular functions. METHODS: We tested the
expression of Orai1 by q-RT-PCR and flow cytometry. Further, we measured SOCE by
an inverted phase-contrast microscope with the Incident-light fluorescence
illumination system using Fura-2. Intracellular Ca2+ was also measured by flow
cytometry using Ca2+ sensitive dye Fluo-4. RESULTS: We found that in Dicer
deficient (DicerDelta/Delta) mice Orai1 was downregulated at mRNA and protein
level in CD4+ T cells. Further, SOCE was significantly smaller in
DicerDelta/Delta CD4+ T cells than in CD4+ T cells isolated from wild-type
(Dicerfl/fl) mice. CONCLUSION: Our data suggest that miRNAs are required for
adequate Ca2+ entry into CD4+ T cells and thus triggering of Ca2+ sensitive
immune functions.
PMID- 27607423
TI - Energy Sprawl Is the Largest Driver of Land Use Change in United States.
AB - Energy production in the United States for domestic use and export is predicted
to rise 27% by 2040. We quantify projected energy sprawl (new land required for
energy production) in the United States through 2040. Over 200,000 km2 of
additional land area will be directly impacted by energy development. When
spacing requirements are included, over 800,000 km2 of additional land area will
be affected by energy development, an area greater than the size of Texas. This
pace of development in the United States is more than double the historic rate of
urban and residential development, which has been the greatest driver of
conversion in the United States since 1970, and is higher than projections for
future land use change from residential development or agriculture. New
technology now places 1.3 million km2 that had not previously experienced oil and
gas development at risk of development for unconventional oil and gas. Renewable
energy production can be sustained indefinitely on the same land base, while
extractive energy must continually drill and mine new areas to sustain
production. We calculated the number of years required for fossil energy
production to expand to cover the same area as renewables, if both were to
produce the same amount of energy each year. The land required for coal
production would grow to equal or exceed that of wind, solar and geothermal
energy within 2-31 years. In contrast, it would take hundreds of years for oil
production to have the same energy sprawl as biofuels. Meeting energy demands
while conserving nature will require increased energy conservation, in addition
to distributed renewable energy and appropriate siting and mitigation.
PMID- 27607424
TI - HIV Protease Inhibitors Apoptotic Effect in SH-SY5Y Neuronal Cell Line.
AB - BACKGROUND: Prophylactic treatment regimens to prevent mother-to-child HIV
transmission include protease inhibitors Lopinavir and Ritonavir. Lopinavir and
Ritonavir have been reported to be able to induce intracellular oxidative stress
in diverse cellular models, however scarce informations are available about
protease inhibitor effects of in the central nervous system (CNS). In our study
we evaluated the impact of protease inhibitors on a cell neuronal model. METHODS:
We treated a neuroblastoma cell line (SH-SY5Y) with increasing doses of Lopinavir
and Ritonavir (0.1-1-10-25-50 uM), used alone or in combination, evaluating the
impact of these drugs in terms of mitochondrial activity, with MTT cell
proliferation assay; mRNA expression of heme oxygenase (HemeOH) and reactive
oxygen species (ROS) levels with 2',7'-dichlorofluorescin diacetate (H2DCFDA) in
order to assess oxidative stress; apoptotic cell death with flow cytometry.
RESULTS: We observed that Lopinavir and Ritonavir treatment, at 25 and/or 50 uM
concentrations, induced mitochondrial damage, increase of heme oxygenase RNA
expression levels and ROS generation, followed by apoptosis in SH-SY5Y.
CONCLUSIONS: Our in vitro model demonstrates a damaging effect of HIV protease
inhibitors on the neuroblastoma cell line, thus partially mimicking the impact of
these drugs on the CNS of children born to HIV positive mothers undergone to
antiretroviral treatment.
PMID- 27607425
TI - Selective Ion Transporting Polymerized Ionic Liquid Membrane Separator for
Enhancing Cycle Stability and Durability in Secondary Zinc-Air Battery Systems.
AB - Rechargeable secondary zinc-air batteries with superior cyclic stability were
developed using commercial polypropylene (PP) membrane coated with polymerized
ionic liquid as separators. The anionic exchange polymer was synthesized
copolymerizing 1-[(4-ethenylphenyl)methyl]-3-butylimidazolium hydroxide (EBIH)
and butyl methacrylate (BMA) monomers by free radical polymerization for both
functionality and structural integrity. The ionic liquid induced copolymer was
coated on a commercially available PP membrane (Celguard 5550). The coat allows
anionic transfer through the separator and minimizes the migration of zincate
ions to the cathode compartment, which reduces electrolyte conductivity and may
deteriorate catalytic activity by the formation of zinc oxide on the surface of
the catalyst layer. Energy dispersive X-ray spectroscopy (EDS) data revealed the
copolymer-coated separator showed less zinc element in the cathode, indicating
lower zinc crossover through the membrane. Ion coupled plasma optical emission
spectroscopy (ICP-OES) analysis confirmed over 96% of zincate ion crossover was
reduced. In our charge/discharge setup, the constructed cell with the ionic
liquid induced copolymer casted separator exhibited drastically improved
durability as the battery life increased more than 281% compared to the pure
commercial PP membrane. Electrochemical impedance spectroscopy (EIS) during the
cycle process elucidated the premature failure of cells due to the zinc crossover
for the untreated cell and revealed a substantial importance must be placed in
zincate control.
PMID- 27607428
TI - Correction: MRI Background Parenchymal Enhancement Is Not Associated with Breast
Cancer.
AB - [This corrects the article DOI: 10.1371/journal.pone.0158573.].
PMID- 27607426
TI - Reproducibility and Validity of the 6-Minute Walk Test Using the Gait Real-Time
Analysis Interactive Lab in Patients with COPD and Healthy Elderly.
AB - BACKGROUND: The 6-minute walk test (6MWT) in a regular hallway is commonly used
to assess functional exercise capacity in patients with chronic obstructive
pulmonary disease (COPD). However, treadmill walking might provide additional
advantages over overground walking, especially if virtual reality and self-paced
treadmill walking are combined. Therefore, this study aimed to assess the
reproducibility and validity of the 6MWT using the Gait Real-time Analysis
Interactive Lab (GRAIL) in patients with COPD and healthy elderly.
METHODOLOGY/RESULTS: Sixty-one patients with COPD and 48 healthy elderly
performed two 6MWTs on the GRAIL. Patients performed two overground 6MWTs and
healthy elderly performed one overground test. Differences between consecutive
6MWTs and the test conditions (GRAIL vs. overground) were analysed. Patients
walked further in the second overground test (24.8 m, 95% CI 15.2-34.4 m,
p<0.001) and in the second GRAIL test (26.8 m, 95% CI 13.9-39.6 m). Healthy
elderly improved their second GRAIL test (49.6 m, 95% CI 37.0-62.3 m). The GRAIL
6MWT was reproducible (intra-class coefficients = 0.65-0.80). The best GRAIL 6
minute walk distance (6MWD) in patients was shorter than the best overground 6MWD
(-27.3 +/- 49.1 m, p<0.001). Healthy elderly walked further on the GRAIL than in
the overground condition (23.6 +/- 41.4 m, p<0.001). Validity of the GRAIL 6MWT
was assessed and intra-class coefficient values ranging from 0.74-0.77 were
found. CONCLUSION: The GRAIL is a promising system to assess the 6MWD in patients
with COPD and healthy elderly. The GRAIL 6MWD seems to be more comparable to the
6MWDs assessed overground than previous studies on treadmills have reported.
Furthermore, good construct validity and reproducibility were established in
assessing the 6MWD using the GRAIL in patients with COPD and healthy elderly.
PMID- 27607430
TI - Asymmetric Synthesis of Octahydroindoles via a Domino Robinson Annulation/5-Endo
Intramolecular Aza-Michael Reaction.
AB - A straightforward, two-step asymmetric synthesis of octahydroindoles has been
developed on the basis of two complementary strategies: (i) an organocatalyzed
Michael reaction followed by a tandem Robinson-aza-Michael double cyclization
catalyzed by PS-BEMP, and (ii) a diastereoselective cyclization, which formally
constitutes a remote 1,6 asymmetric induction mediated by PS-BEMP. This allowed
the construction of complex octahydroindoles with up to four stereocenters,
excellent enantioselectivities (up to 95% ee), and complete diastereoselective
control in a single-pot operation. DFT calculations were performed to understand
the origin of this effect.
PMID- 27607427
TI - SDF1 Polymorphisms Influence Outcome in Patients with Symptomatic Cardiovascular
Disease.
AB - BACKGROUND: SDF1 and its cognate receptors CXCR4 and CXCR7 are involved in
myocardial repair and are associated with outcome in cardiovascular patients.
Hence, we aimed to investigate clinically significant SDF1 SNPs for their
prognostic impact in patients with cardiovascular disease. METHODS AND RESULTS:
Genotyping for selected SDF1 variants (rs1065297, rs2839693, rs1801157, rs266087,
rs266085 and rs266089 was performed in patients (n = 872) who underwent
percutaneous coronary intervention. Carriers of variant rs2839693 and rs266089
showed significantly higher cumulative event-free survival compared with non
carriers. All other polymorphisms had no relevant influence on outcome.
Multivariate Cox regression analysis showed a significant correlation of these
SNPs with cardiovascular outcome after inclusion of clinical and prognostic
relevant variables (hazard ratio (HR) 0.51 (95% CI 0.30-0.88), p = 0.015 and [HR
0.51 (95% CI 0.30-0.88), p = 0.016, respectively). In addition, multivariate Cox
regression with SDF1 haplotypes revealed a significantly reduced risk for the
haplotype carrying the minor alleles of rs2839693 and rs266089 (HR 0.47 (95% CI
0.27-0.84), p = 0.011). CONCLUSION: Distinct SDF1 polymorphisms are associated
with improved cardiovascular prognosis in CAD patients. Further studies are
warranted to validate these results and to better describe the endogenous
regeneration potential in carriers of these SNPs. Targeted, genotype guided
therapeutic approaches to foster myocardial regeneration and thus cardiovascular
prognosis should be evaluated in future.
PMID- 27607429
TI - Alpha1-Antitrypsin Attenuates Renal Fibrosis by Inhibiting TGF-beta1-Induced
Epithelial Mesenchymal Transition.
AB - Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating
the activity of serine proteinases. This study evaluated the inhibitory effects
of AAT against the transforming growth factor (TGF)-beta1 induced epithelial-to
mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and
Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were
injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells
were treated with TGF-beta1 (2 ng/mL) for 48 hours to induce EMT, and co-treated
with AAT (10 mg/mL) to inhibit the EMT. Masson's trichrome and Sirius red
staining was used to estimate the extent of renal fibrosis in UUO mice. The
expression of alpha-smooth muscle actin (alpha-SMA), vimentin, fibronectin,
collagen I, and E-cadherin in MDCK cells and kidney tissue were evaluated.
Masson's and Sirius red staining revealed that the area of renal fibrosis was
significantly smaller in AAT treated UUO group compared with that of UUO and
vehicle treated UUO groups. AAT treatment attenuated upregulation of Smad2/3
phosphorylation in UUO mouse model. Co-treatment of MDCK cells with TGF-beta1 and
AAT significantly attenuated the changes in the expression of alpha-SMA,
vimentin, fibronectin, collagen I, and E-cadherin. AAT also decreased the
phosphorylated Smad3 expression and the phosphorylated Smad3/Smad3 ratio in MDCK
cells. AAT treatment inhibited EMT induced by TGF-beta1 in MDCK cells and
attenuated renal fibrosis in the UUO mouse model. The results of this work
suggest that AAT could inhibit the process of EMT through the suppression of TGF
beta/Smad3 signaling.
PMID- 27607432
TI - [About the Reduction of Compulsory Measures by an "Open Door Policy"].
PMID- 27607431
TI - Phase and Frequency-Dependent Effects of Transcranial Alternating Current
Stimulation on Motor Cortical Excitability.
AB - Transcranial alternating current stimulation (tACS) can entrain ongoing brain
oscillations and modulate the motor system in a frequency-dependent manner.
Recent animal studies have demonstrated that the phase of a sinusoidal current
also has an important role in modulation of neuronal activity. However, the phase
effects of tACS on the human motor system are largely unknown. Here, we
systematically investigated the effects of tACS phase and frequency on the
primary motor cortex (M1) by using motor evoked potentials (MEPs) with
transcranial magnetic stimulation (TMS). First, we compared the phase effects (90
degrees , 180 degrees , 270 degrees or 360 degrees ) of 10 and 20 Hz tACS on
MEPs. The 20 Hz tACS significantly increased M1 excitability compared with the 10
Hz tACS at 90 degrees phase only. Second, we studied the 90 degrees phase
effect on MEPs at different tACS frequencies (5, 10, 20 or 40 Hz). The 20 vs. 10
Hz difference was again observed, but the 90 degrees phase in 5 and 40 Hz tACS
did not influence M1 excitability. Third, the 90 degrees phase effects of 10 and
20 Hz tACS were compared with sham stimulation. The 90 degrees phase of 20 Hz
tACS enhanced MEP amplitudes compared with sham stimulation, but there was no
significant effect of 10 Hz tACS. Taken together, we assume that the differential
90 degrees phase effects on 20 Hz and 10 Hz tACS can be attributed to the neural
synchronization modulated by tACS. Our results further underline that phase and
frequency are the important factors in the effects of tACS on M1 excitability.
PMID- 27607433
TI - [Ministerial Draft Bill for the Law on Remuneration of Inpatient Psychiatry and
Psychosomatics (Psych VVG): We are Headed in the Right Direction - Pro].
PMID- 27607434
TI - [Ministerial Draft Bill for the Law on Remuneration of Inpatient Psychiatry and
Psychosomatics (Psych VVG): We are Headed in the Right Direction - Contra].
PMID- 27607435
TI - [Not Available].
PMID- 27607436
TI - Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/TAF15-ZNF384 and Other
Chromosome Abnormalities.
AB - The t(12;17)(p13;q11~21) translocation is a very rare but recurrent cytogenetic
aberration observed predominantly in early pre-B acute lymphoblastic leukemia
(ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a
fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand,
der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation
leading to trisomy 1q in myeloid malignancies. We describe here the first case of
mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384,
which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old
woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were
positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX,
+1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15
ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384
exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia
case and 3 ALL cases. Thus, at present, it is difficult to find a specific
association between the structure of the TAF15-ZNF384 fusion gene and the
leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor
cells that could differentiate into both the myeloid and lymphoid lineages.
Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an
additional myeloid phenotype.
PMID- 27607437
TI - Economic Evaluation of Complementary and Alternative Medicine in Oncology: Is
There a Difference Compared to Conventional Medicine?
AB - OBJECTIVE: To analyze the financial burden of complementary and alternative
medicine (CAM) in cancer treatment. MATERIALS AND METHODS: Based on a systematic
search of the literature (Medline and the Cochrane Library, combining the MeSH
terms 'complementary therapies', 'neoplasms', 'costs', 'cost analysis', and 'cost
benefit analysis'), an expert panel discussed different types of analyses and
their significance for CAM in oncology. RESULTS: Of 755 publications, 43 met our
criteria. The types of economic analyses and their parameters discussed for CAM
in oncology were cost, cost-benefit, cost-effectiveness, and cost-utility
analyses. Only a few articles included arguments in favor of or against these
different methods, and only a few arguments were specific for CAM because most
CAM methods address a broad range of treatment aim parameters to assess
effectiveness and are hard to define. Additionally, the choice of comparative
treatments is difficult. To evaluate utility, healthy subjects may not be
adequate as patients with a life-threatening disease and may be judged
differently, especially with respect to a holistic treatment approach. We did not
find any arguments in the literature that were directed at the economic analysis
of CAM in oncology. Therefore, a comprehensive approach assessment based on
criteria from evidence-based medicine evaluating direct and indirect costs is
recommended. CONCLUSION: The usual approaches to conventional medicine to assess
costs, benefits, and effectiveness seem adequate in the field of CAM in oncology.
Additionally, a thorough deliberation on the comparator, endpoints, and
instruments is mandatory for designing studies.
PMID- 27607438
TI - Integrative versus Conventional Therapy of Chronic Otitis Media with Effusion and
Adenoid Hypertrophy in Children: A Prospective Observational Study.
AB - BACKGROUND: Chronic otitis media with effusion (COME) and adenoid hypertrophy
(AH) are common entities in the pediatric population. The conventional treatment
approach (conventional medicine; COM) involved mainly surgery after a period of
close observation. In this study, we aimed to introduce an integrative, non
invasive approach (integrative medicine; IM) for COME, AH, and associated
episodes of recurrent acute otitis media, and compared outcomes with conventional
treatment. METHODS: We conducted a prospective, non-randomized study in an
integrative primary care pediatric practice and a conventional pediatric
otolaryngological clinic, where treatment modality was determined by patient
preference. Out of a total 101 patients aged 1-8 years, integrative therapy was
chosen by 46, and conventional treatment by 55. All patients had COME and AH
diagnosed by an otolaryngologist and had moderate to severe hearing impairment.
COM treatment was based on close observation over time, nasal decongestants and
surgical intervention. In contrast, the IM involved a complex personalized
approach with non-invasive interventions, non-allopathic medications, diet and
patient education. RESULTS: The number of surgical interventions (adenoidectomy,
pressure-equalization tube insertion, myringotomy) was significantly less in the
IM cohort (1 of 28 vs. 15 of 35 in the COM group, p < 0.001). The frequency of
antibiotic use was significantly less in the IM group (p < 0.001). The frequency
of analgesic use was also significantly less in the IM group (p = 0.029).
Improvement in tympanometric measures (normal A-type curve) was higher in IM
patients compared to expected spontaneous remission during the observation
period. Improvement in audiometric measures (intact hearing) of IM patients was
also higher than expected compared to spontaneous remission during the
observation period. CONCLUSION: Compared to conventional treatment, integrative
treatment of patients with COME and AH showed significantly lower invasive
surgical intervention rates and significantly decreased antibiotic and analgesic
use. The integrative treatment was effective, safe and well tolerated.
PMID- 27607439
TI - Attention Network Dysfunction in Bulimia Nervosa - An fMRI Study.
AB - OBJECTIVE: Recent evidence has suggested an increased rate of comorbid ADHD and
subclinical attentional impairments in bulimia nervosa (BN) patients. However,
little is known regarding the underlying neural mechanisms of attentional
functions in BN. METHOD: Twenty BN patients and twenty age- and weight-matched
healthy controls (HC) were investigated using a modified version of the Attention
Network Task (ANT) in an fMRI study. This design enabled an investigation of the
neural mechanisms associated with the three attention networks involved in
alerting, reorienting and executive attention. RESULTS: The BN patients showed
hyperactivation in parieto-occipital regions and reduced deactivation of default
mode-network (DMN) areas during alerting compared with HCs. Posterior cingulate
activation during alerting correlated with the severity of eating-disorder
symptoms within the patient group. Conversely, BN patients showed hypoactivation
during reorienting and executive attention in anterior cingulate regions, the
temporo-parietal junction (TPJ) and parahippocampus compared with HCs, which was
negatively associated with global ADHD symptoms and impulsivity, respectively.
DISCUSSION: Our findings demonstrate altered brain mechanisms in BN associated
with all three attentional networks. Failure to deactivate the DMN and increased
parieto-occipital activation required for alerting might be associated with a
constant preoccupation with food or body image-related thoughts. Hypoactivation
of executive control networks and TPJ might increase the likelihood of
inattentive and impulsive behaviors and poor emotion regulation. Thus,
dysfunction in the attentional network in BN goes beyond an altered executive
attentional domain and needs to be considered in the diagnosis and treatment of
BN.
PMID- 27607441
TI - Facet to Facet Linking of Shape Anisotropic Inorganic Nanocrystals with Site
Specific and Stoichiometric Control.
AB - Nonclassical growth mechanisms such as self-assembly and oriented attachment are
effective ways to build complex nanostructures from simpler ones. In the latter
case, the nanoparticle components are electronically coupled; however, control
over the attachment between nanoparticles is highly challenging and generally
requires a delicate balance between dipole-, ligand-, and solvent-based
interactions. To this end, we perform incomplete cation exchange with Ag+ (Cu+)
on CdSe-seeded CdS nanorods and tetrapods to exclusively convert their tips into
small Ag2S (Cu2S) domains. Selective removal of the ligands from these inorganic
domains results in spontaneous, site-specific bridging of the nanoparticles.
Using this method, we demonstrate the fabrication of polymer-like linear and
branched nanoparticles with enhanced electrical properties, as well as the
stoichiometric formation of nanoparticle homo- and heterodimers and tetramers. We
show that linked structures can then be completely cation exchanged with Pb2+ to
generate PbSe/PbS-based nanostructured photodetector media with enhanced
properties.
PMID- 27607442
TI - Giordano Bruno and the heresy of many worlds.
AB - This paper analyses the importance of Giordano Bruno's belief in many worlds,
including the Moon, the planets and the stars, in the context of his trial by the
Inquisitions in Venice and Rome. Historians have claimed that this belief was not
heretical and therefore was not a major factor in Bruno's trial or execution. On
the contrary, by examining neglected treatises on theology, heresies and Catholic
canon law, I show that the belief in many worlds was formally heretical. Multiple
Christian authorities denounced it. A systematic analysis of the extant primary
sources shows that Bruno's belief in many worlds was, surprisingly, of primary
importance in his trial and execution. The evidence includes recent and newly
discovered primary sources.
PMID- 27607440
TI - De Novo Herpes Simplex Virus VP16 Expression Gates a Dynamic Programmatic
Transition and Sets the Latent/Lytic Balance during Acute Infection in Trigeminal
Ganglia.
AB - The life long relationship between herpes simplex virus and its host hinges on
the ability of the virus to aggressively replicate in epithelial cells at the
site of infection and transport into the nervous system through axons innervating
the infection site. Interaction between the virus and the sensory neuron
represents a pivot point where largely unknown mechanisms lead to a latent or a
lytic infection in the neuron. Regulation at this pivot point is critical for
balancing two objectives, efficient widespread seeding of the nervous system and
host survival. By combining genetic and in vivo in approaches, our studies reveal
that the balance between latent and lytic programs is a process occurring early
in the trigeminal ganglion. Unexpectedly, activation of the latent program
precedes entry into the lytic program by 12 -14hrs. Importantly, at the
individual neuronal level, the lytic program begins as a transition out of this
acute stage latent program and this escape from the default latent program is
regulated by de novo VP16 expression. Our findings support a model in which
regulated de novo VP16 expression in the neuron mediates entry into the lytic
cycle during the earliest stages of virus infection in vivo. These findings
support the hypothesis that the loose association of VP16 with the viral tegument
combined with sensory axon length and transport mechanisms serve to limit arrival
of virion associated VP16 into neuronal nuclei favoring latency. Further, our
findings point to specialized features of the VP16 promoter that control the de
novo expression of VP16 in neurons and this regulation is a key component in
setting the balance between lytic and latent infections in the nervous system.
PMID- 27607443
TI - An alternative method to quantify 2-MIB producing cyanobacteria in drinking water
reservoirs: Method development and field applications.
AB - 2-Methylisoborneol (2-MIB) is a commonly detected cyanobacterial odorant in
drinking water sources in many countries. To provide safe and high-quality water,
development of a monitoring method for the detection of 2-MIB-synthesis (mibC)
genes is very important. In this study, new primers MIBS02F/R intended
specifically for the mibC gene were developed and tested. Experimental results
show that the MIBS02F/R primer set was able to capture 13 2-MIB producing
cyanobacterial strains grown in the laboratory, and to effectively amplify the
targeted DNA region from 17 2-MIB-producing cyanobacterial strains listed in the
literature. The primers were further coupled with a TaqMan probe to detect 2-MIB
producers in 29 drinking water reservoirs (DWRs). The results showed
statistically significant correlations between mibC genes and 2-MIB
concentrations for the data from each reservoir (R2=0.413-0.998; p<0.05), from
all reservoirs in each of the three islands (R2=0.302-0.796; p<0.01), and from
all data of the three islands (R2=0.473-0.479; p<0.01). The results demonstrate
that the real-time PCR can be an alternative method to provide information to
managers of reservoirs and water utilities facing 2-MIB-related incidents.
PMID- 27607444
TI - Whole blood: back to the future.
AB - PURPOSE OF REVIEW: We present data comparing whole blood with blood components
and summarize the data that support increased availability of whole blood for
patients with life-threatening bleeding. RECENT FINDINGS: Recent data indicate
that whole-blood transfusion is associated with improved or comparable survival
compared with resuscitation with blood components. These data complement
randomized controlled trials indicating that platelet-containing blood products
stored at 4 degrees C have superior hemostatic function, compared with platelet
containing blood products at 22 degrees C. Whole blood is rarely available in
civilian hospitals and, thus, is rarely transfused into patients with hemorrhagic
shock. Misconceptions that whole blood must be ABO specific, that whole blood
cannot be leukoreduced and maintain platelets, and that cold storage causes loss
of platelet function have limited its availability. Understanding that these
barriers are not insurmountable will improve the availability of whole blood and
facilitate its use. In addition, there are logistical advantages of whole-blood
based resuscitation, as compared with component therapy, for hemorrhagic shock.
SUMMARY: Low titer Group O whole blood stored for up to 21 days at 4 degrees C
merits further study to compare its efficacy and safety with current
resuscitation approaches for patients with life-threatening bleeding.
PMID- 27607446
TI - Allogeneic hematopoietic stem cell transplantation for dyskeratosis congenita.
AB - PURPOSE OF REVIEW: Dyskeratosis congenita is an inherited bone marrow failure
syndrome caused by defects in telomere maintenance. Hematopoietic stem cell
transplantation (HSCT) is the only curative treatment for bone marrow failure
because of dyskeratosis congenita. The present review summarizes the literature
with respect to the diagnosis and treatment of patients with dyskeratosis
congenita who received HSCT, and discusses the recent progress in the management
of dyskeratosis congenita. RECENT FINDINGS: The recent systematic review of the
literature showed poor long-term outcome, with 10-year survival estimates of only
23% in 109 patients with dyskeratosis congenita who received HSCT. Multivariate
analysis identified age greater than 20 years at HSCT, HSCT before 2000, and
alternative donor source to be poor prognostic markers. HSCT for dyskeratosis
congenita is characterized by a marked decline in long-term survival because of
late deaths from pulmonary complications. However, a prospective study using
danazol showed promising results in gain in telomere length and hematologic
responses. SUMMARY: A recent prospective study may support the recommendation
that HSCT is not indicated for patients with dyskeratosis congenita; instead,
they should receive androgen, particularly danazol, as a first-line therapy.
Another option may be routine use of androgen after HSCT for the prophylaxis of
pulmonary fibrosis.
PMID- 27607445
TI - Hematopoietic stem cell transplantation for acquired aplastic anemia.
AB - PURPOSE OF REVIEW: There has been a steady improvement in outcomes with
allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA),
because of progress in optimization of the conditioning regimens, donor
hematopoietic cell source, and supportive care. Here, we review recently
published data that highlight the improvements and current issues in the
treatment of SAA. RECENT FINDINGS: Approximately one-third of aplastic anemia
patients treated with immune suppressive therapy (IST) have acquired mutations in
myeloid cancer candidate genes. Because of the greater probability for eventual
failure of IST, human leukocyte antigen (HLA)-matched sibling donor BMT is the
first-line of treatment for SAA. HLA-matched unrelated donor (URD) BMT is
generally recommended for patients who have failed IST. However, in younger
patients for whom a 10/10-HLA-allele matched URD can be rapidly identified, there
is a strong rationale to proceed with URD BMT as first-line therapy. HLA
haploidentical BMT using posttransplant cyclophosphamide conditioning regimens is
now a reasonable second-line treatment for patients who failed IST. SUMMARY:
Improved outcomes have led to an increased first-line role of BMT for treatment
of SAA. The optimal cell source from an HLA-matched donor is bone marrow.
Additional studies are needed to determine the optimal conditioning regimen for
HLA-haploidentical donors.
PMID- 27607448
TI - Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of
Mesenchymal Stem Cells via Suppressing Mitochondrial ROS.
AB - BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have the
ability to differentiate into multilineage cells such as osteoblasts,
chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to
pathological stimuli participates in the development of diseases such as
osteoporosis. Astragalus polysaccharide (APS) is a major active ingredient of
Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese
medicine. The aim of this study was to investigate whether APS protects against
iron overload-induced dysfunction of BMSCs and its underlying mechanisms.
METHODS: BMSCs were exposed to ferric ammonium citrate (FAC) with or without
different concentrations of APS. The viability and proliferation of BMSCs were
assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and
pluripotency were examined utilizing TUNEL staining, beta-galactosidase staining
and qRT-PCR respectively. The reactive oxygen species (ROS) level was assessed in
BMSCs with a DCFH-DA probe and MitoSOX Red staining. RESULTS: Firstly, we found
that iron overload induced by FAC markedly reduced the viability and
proliferation of BMSCs, but treatment with APS at 10, 30 and 100 MUg/mL was able
to counter the reduction of cell proliferation. Furthermore, exposure to FAC led
to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The
pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs
after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4
expression. Further study uncovered that APS treatment abrogated the increase of
intracellular and mitochondrial ROS level in FAC-treated BMSCs. CONCLUSION:
Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can
remarkably inhibit apoptosis, senescence, and the reduction of proliferation and
pluripotency of BMSCs caused by FAC-induced iron overload.
PMID- 27607450
TI - The rs9932581 and rs1049255 Polymorphisms in CYBA is not Associated with
Preeclampsia in Chinese Han Women.
AB - BACKGROUND/AIMS: Several lines of evidence have been reported that oxidative
stress plays an important role in the pathogenesis of Preeclampsia (PE).
Therefore, this research is aimed to investigate whether polymorphisms of CYBA
are related to susceptibility to PE in Chinese Han women. METHODS: We studied the
genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE
patients and 1400 controls of later pregnant women by the TaqMan allelic
discrimination real-time PCR and a case-control model. RESULTS: Our research
indicated that no significant differences were found for the genotypic or allelic
frequencies at the two polymorphic sites in CYBA between PE patients and
controls. To further study the relationship between the polymorphic sites and PE,
we also found that there is no significant difference in the genetic
distributions identified between the mild or severe PE and early or the late
onset PE and controls. CONCLUSION: The study demonstrated that the genetic
variants of rs9932581 and rs1049255 in CYBA might not be associated with PE.
However, investigations of genetic variability that influence on the disease
outcome are needed in other large prospective populations or regions, so the
complicated interconnection of genetic and environmental elements can be emulated
for better understanding.
PMID- 27607451
TI - Leadership and emotional intelligence in nursing and midwifery education and
practice: a discussion paper.
AB - AIM: A discussion of the concepts of leadership and emotional intelligence in
nursing and midwifery education and practice. BACKGROUND: The need for
emotionally intelligent leadership in the health professions is acknowledged
internationally throughout the nursing and midwifery literature. The concepts of
emotional intelligence and emotional-social intelligence have emerged as
important factors for effective leadership in the healthcare professions and
require further exploration and discussion. This paper will explore these
concepts and discuss their importance in the healthcare setting with reference to
current practices in the UK, Ireland and internationally. DESIGN: Discussion
paper. DATA SOURCES: A search of published evidence from 1990-2015 using key
words (as outlined below) was undertaken from which relevant sources were
selected to build an informed discussion. IMPLICATIONS FOR NURSING/MIDWIFERY:
Fostering emotionally intelligent leadership in nursing and midwifery supports
the provision of high quality and compassionate care. Globally, leadership has
important implications for all stakeholders in the healthcare professions with
responsibility for maintaining high standards of care. This includes all grades
of nurses and midwives, students entering the professions, managerial staff,
academics and policy makers. CONCLUSION: This paper discusses the conceptual
models of leadership and emotional intelligence and demonstrates an important
link between the two. Further robust studies are required for ongoing evaluation
of the different models of emotional intelligence and their link with effective
leadership behaviour in the healthcare field internationally. This is of
particular significance for professional undergraduate education to promote
ongoing compassionate, safe and high quality standards of care.
PMID- 27607449
TI - GNAI3: Another Candidate Gene to Screen in Persons with Ocular Albinism.
AB - Ocular albinism type 1 (OA), caused by mutations in the OA1 gene, encodes a G
protein coupled receptor, OA1, localized in melanosomal membranes of the retinal
pigment epithelium (RPE). This disorder is characterized by both RPE macro
melanosomes and abnormal decussation of ganglion cell axons at the brain's optic
chiasm. We demonstrated previously that Oa1 specifically activates Galphai3,
which also signals in the Oa1 transduction pathway that regulates melanosomal
biogenesis. In this study, we screened the human Galphai3 gene, GNAI3, in DNA
samples from 26 patients who had all clinical characteristics of OA but in whom a
specific mutation in the OA1 gene had not been found, and in 6 normal control
individuals. Using the Agilent HaloPlex Target Enrichment System and next
generation sequencing (NGS) on the Illumina MiSeq platform, we identified 518
variants after rigorous filtering. Many of these variants were corroborated by
Sanger sequencing. Overall, 98.8% coverage of the GNAI3 gene was obtained by the
HaloPlex amplicons. Of all variants, 6 non-synonymous and 3 synonymous were in
exons, 41 in a non-coding exon embedded in the 3' untranslated region (UTR), 6 in
the 5' UTR, and 462 in introns. These variants included novel SNVs, insertions,
deletions, and a frameshift mutation. All were found in at least one patient but
none in control samples. Using computational methods, we modeled the GNAI3
protein and its non-synonymous exonic mutations and determined that several of
these may be the cause of disease in the patients studied. Thus, we have
identified GNAI3 as a second gene possibly responsible for X-linked ocular
albinism.
PMID- 27607452
TI - Exposure to the Chinese famine in early life and hypertension prevalence risk in
adults.
AB - OBJECTIVES: Famine exposure in early life has been reported to be associated with
higher risk of hypertension prevalence in adults. The aim of the present study
was to investigate the association of exposure to the Chinese famine during early
life with the risk of hypertension prevalence in adults. METHODS: There were 8742
participants born between 1952 and 1964 derived from the Dongfeng-Tongji cohort
included in the present study. Participants were classified as nonexposed group,
fetal exposed group, early-childhood exposed group, mid-childhood exposed group,
and late-childhood exposed group, respectively. Logistic regression model was
used to explore the association between famine exposure in early life and risk of
hypertension prevalence in adults. RESULTS: The prevalence of hypertension among
individuals in nonexposed group, fetal exposed group, early-childhood exposed
group, mid-childhood exposed group, and late-childhood exposed group were 34.0,
38.0, 43.9, 47.4, and 54.4%, respectively. Compared with nonexposed group,
participants exposed to the famine in the fetal [1.24, 95% confidence interval
(CI): 1.01-1.51], early childhood (1.44, 95% CI: 1.20-1.73), mid-childhood (1.67,
95% CI: 1.38-2.02), and late childhood (2.11, 95% CI: 1.75-2.55) had higher risk
of hypertension prevalence in adults after adjustment for potential confounders
(P for trend <0.0001). Adjustment for age did not materially change the results.
CONCLUSION: Results in the present study indicated that exposure to the famine in
early life increases the risk of hypertension prevalence in adulthood.
PMID- 27607453
TI - Effects of metformin on blood pressure in nondiabetic patients: a meta-analysis
of randomized controlled trials.
AB - OBJECTIVE: To evaluate the effects of metformin on systolic blood pressure (SBP)
and diastolic blood pressure (DBP) in nondiabetic patients. METHODS: In this meta
analysis, we systematically searched PubMed, Embase, and the Cochrane Library
through March 2016, and randomized controlled trials assessing the effects of
metformin treatment compared with placebo were included. Random-effects models
were used to estimate pooled mean differences in SBP and DBP. RESULTS: Twenty
eight studies from 26 articles consisting of 4113 participants were included.
Pooled results showed that metformin had a significant effect on SBP (mean
difference -1.98 mmHg; 95% confidence interval -3.61, -0.35; P = 0.02), but not
on DBP (mean difference -0.67 mmHg; 95% confidence interval -1.74, 0.41; P =
0.22). In subgroup analysis, we found that the effect of metformin on SBP was
significant in patients with impaired glucose tolerance or obesity (BMI >=30
kg/m), with a mean reduction of 5.03 and 3.00 mmHg, respectively. Significant
heterogeneity was found for both SBP (I = 60.0%) and DBP (I = 45.4%). A
sensitivity analysis indicated that the pooled effects of metformin on SBP and
DBP were robust to systematically dropping each trial. Furthermore, no evidence
of significant publication bias from funnel plots or Egger's tests (P = 0.51 and
0.21 for SBP and DBP, respectively) was found. CONCLUSION: This meta-analysis
suggested that metformin could effectively lower SBP in nondiabetic patients,
especially in those with impaired glucose tolerance or obesity.
PMID- 27607454
TI - Effects of muscle strength and endurance on blood pressure and related
cardiometabolic risk factors from childhood to adolescence.
AB - OBJECTIVE: This study aimed to examine the evolution of relationships between
measures of muscle strength and endurance with individual cardiometabolic risk
factors from childhood to late adolescence in a prospective population-based
cohort. METHODS: Participants from the Western Australian Pregnancy Cohort
(Raine) Study at ages 10, 14 and 17 were analysed, using longitudinal linear
mixed model analyses. RESULTS: Handgrip strength after adjusting for the
confounding effects of BMI was positively associated with SBP, but not DBP. The
association between handgrip strength and SBP was stronger in men than women at
all time points [coefficient (women): 0.18, P < 0.001; sex * handgrip strength
coefficient: 0.09, P = 0.002]. The association was strongest at 10 years and
significantly attenuated over time (year * handgrip coefficient from 10 to 14
years: -0.11, P = 0.003; year * handgrip coefficient from 10 to 17 years: -0.19,
P <= 0.001). After the inclusion of BMI as a confounder, handgrip strength was
significantly negatively associated with homeostatic model assessment of insulin
resistance and high-sensitivity C-reactive protein over time in both sexes. Back
muscle endurance was positively associated with SBP, but not DBP, after
adjustment for the confounding effects of BMI (coefficient: 0.01, P = 0.002).
There were small, albeit significant, inverse associations between back muscle
endurance and log homeostatic model assessment of insulin resistance and log high
sensitivity C-reactive protein. CONCLUSION: The positive association between
handgrip strength and back muscle endurance with SBP throughout childhood and
adolescence contrasts with beneficial effects on other related traditional
cardiometabolic risk factors. Mechanisms underlying these paradoxical effects on
SBP warrant further investigation.
PMID- 27607455
TI - Left ventricular ejection fraction and aortic stiffness are independent
predictors of neurological outcome in acute ischemic stroke.
AB - BACKGROUND: Stroke is a leading cause of disability and one of the major causes
of death worldwide. The short-term prognosis in individual patients is highly
variable and cannot be explained solely by stroke severity. We investigated the
association of left ventricular ejection fraction with early neurological outcome
in acute ischemic stroke. METHODS: In total, 216 patients enrolled in a
prospective study, underwent echocardiography and applanation tonometry performed
within 1 week after stroke onset. At day 10, favorable outcome was defined as a 4
or more point improvement from baseline National Institutes of Health Stroke
Scale or final National Institutes of Health Stroke Scale of 0-1. RESULTS: In
patients with favorable outcome, the ejection fraction was significantly higher
comparing with patients with poorer prognosis (54.3 +/- 7.9 vs. 49.9 +/- 9.8%, P
= 0.005). Favorable neurological outcome at day 10 was also associated with lower
heart rate and lower pulse wave velocity at baseline. Univariate analyses showed
that left ventricle ejection fraction and arterial stiffness were the strongest
predictors of the poststroke improvement. In multivariate analysis, ejection
fraction at least 50% remained significantly associated with favorable outcome
after full adjustment for potential confounders (odds ratio 3.81, [95% confidence
interval, 1.18-12.35]; P = 0.02). CONCLUSION: These findings provide evidence
that in ischemic stroke, preserved ejection fraction and lower pulse wave
velocity are associated with early favorable outcome, independently of other
known prognostic factors, including blood pressure.
PMID- 27607456
TI - Reevaluate secular trends of body size measurements and prevalence of
hypertension among Chinese children and adolescents in past two decades.
AB - OBJECTIVE: This study reevaluated the secular trends of blood pressure and
hypertension prevalence in Chinese children and adolescents by adjusting for
growing body sizes. METHODS: The study population was from the China Health and
Nutrition Survey (1991-2011) and included 7358 boys and 6881 girls aged 8-17
years. Body size measurements and blood pressure were standardized into z-scores
using national references to allow comparisons among different age groups and
survey years. Prehypertension and hypertension rates were defined by using
national and international age-specific and height-specific references. RESULTS:
SBP and DBP increased 0.07 and 0.09 SD per survey year, respectively. BMI, waist
circumference, and height increased 0.14, 0.11, and 0.29 SD, respectively. The
general obesity prevalence increased from 1.5 to 8.1% (Ptrends <= 0.0001), with
an average annual increase (AAI) of 0.36 and 0.42% for urban and rural boys,
respectively, and of 0.33 and 0.22% for urban and rural girls, respectively. The
hypertension prevalence increased from 6.9 to 10.7% (Ptrends <= 0.0001). The
overall AAI in hypertension was 0.19% and was three-fold higher among boys
(0.29%) than among girls (0.09%), explaining the sex difference in the rural
population. The area and sex differences in AAI remained after applying the
international criteria. CONCLUSION: By adjusting for height, the hypertension
prevalence in Chinese children increased 0.19% per year on average over the last
two decades, which is much less than that reported in previous studies. This
trend appears regardless of sex and area and is consistent with the obesity
trend.
PMID- 27607457
TI - Amlodipine and enalapril promote distinct effects on cardiovascular autonomic
control in spontaneously hypertensive rats: the role of aerobic physical
training.
AB - BACKGROUND: We compared the autonomic and hemodynamic cardiovascular effects of
amlodipine and enalapril treatment associated with an aerobic physical training
program on spontaneously hypertensive rats. METHODS: Eighteen-week-old (n = 48)
spontaneously hypertensive rats were assigned to one of two groups: sedentary (n
= 24) and trained (n = 24) through a 10-week swimming training program. Each
group was subdivided into three groups (n = 8): control (vehicle group),
amlodipine (amlodipine group; 10 mg/kg per day) and enalapril (enalapril group;
10 mg/kg per day) (both for 10 weeks). We cannulated the femoral artery and vein
of all animals for recording arterial pressure and injecting drugs, respectively.
Autonomic assessment was performed by double blockade with propranolol and
atropine, analysis of heart rate variability (HRV), systolic arterial pressure
variability and baroflex sensitivity. RESULTS: Arterial pressure reduction was
more prominent in the sedentary and trained enalapril groups. Amlodipine
sedentary group presented important autonomic adjustments characterized by a
predominance of vagal tone in cardiac autonomic balance, increased HRV associated
with sympathetic autonomic modulation reduction and increased vagal autonomic
modulation, and increased baroflex sensitivity. All findings were not
potentialized by physical training. In turn, the enalapril trained group, but not
its sedentary counterpart, also had vagal tone prevalence in cardiac autonomic
balance, increased HRV, increased baroflex sensitivity and decreased low
frequency band in systolic arterial pressure variability. CONCLUSION: Amlodipine
was more effective in promoting beneficial autonomic cardiovascular adaptations
in sedentary animals. In contrast, enalapril achieved better autonomic results
only when combined with aerobic physical training.
PMID- 27607458
TI - The effect of renal denervation in moderate treatment-resistant hypertension with
confirmed medication adherence.
AB - OBJECTIVES: Data on the blood pressure (BP)-lowering effect of renal denervation
(RDN) in moderate treatment-resistant hypertension (TRH) are limited. Moreover,
change of adherence to medication, as one potential confounder of BP response,
has never been analyzed rigorously in this group of patients. We analyzed the
effect of RDN on BP in patients with moderate TRH who were retrospectively found
to be completely adherent to their antihypertensive medication. METHODS: Our
study cohort comprised 40 patients with moderate TRH [office BP >= 140/90 but
<160/100 mmHg and 24-h ambulatory BP monitoring (ABPM) >=130/80 mmHg] who
underwent catheter-based RDN. Further major inclusion criterion was complete
adherence to their medication (>=80% intake of their prescribed antihypertensive
drugs) at baseline (assessed by retrospective toxicological analysis). RESULTS:
Six months after RDN, office BP was reduced by -10/-6 mmHg (SBP: 149 +/- 6 vs.
139 +/- 15 mmHg; DBP: 81 +/- 12 vs. 75 +/- 10 mmHg; both P < 0.001) and 24-h ABPM
by -7/-4 mmHg (SBP: 150 +/- 14 vs. 143 +/- 16 mmHg, P = 0.005; DBP: 82 +/- 10 vs.
78 +/- 9 mmHg, P = 0.009). Number of prescribed antihypertensive medication [6.0
(5.0-6.0) vs. 5.5 (5.0-6.0), P = 0.013] and adherence rate (95.2 +/- 7.6 vs. 91.7
+/- 13.9%, P = 0.065) was slightly reduced 6 months after RDN, both likely to
underestimate the true BP reduction. CONCLUSION: Thus, our data indicate that
even after given full respect to drug adherence as potential confounder of BP
response after RDN, both office and 24-h ABPM were substantially reduced in
patients with moderate TRH.
PMID- 27607459
TI - Modification of the impact of hypertension on proteinuria by renal arteriolar
hyalinosis in nonnephrotic chronic kidney disease.
AB - OBJECTIVE: Morphological analysis suggests that afferent arteriole hyalinosis
reflects disturbed autoregulation of glomerular hemodynamics. However, the effect
of arteriolar hyalinosis on the correlation between blood pressure (BP) levels
and proteinuria is unknown in patients with chronic kidney disease (CKD).
Therefore, we conducted a cross-sectional study to determine this correlation.
METHODS: A total of 109 patients with nonnephrotic CKD (55 men and 54 women) who
underwent renal biopsy were recruited. Arteriolar hyalinosis was
semiquantitatively assessed via arteriole grading. We examined the correlation
between BP and urine protein levels (g/gCr) according to the presence of
arteriolar hyalinosis. RESULT: Patients had a mean age, BP, estimated glomerular
filtration rate, and urine protein level of 40 years, 126/75 mmHg, 86 ml/min per
1.73 m, and 1.3 g/gCr, respectively. Patients with hyalinosis (n = 59) exhibited
significant increases in median proteinuria (g/gCr) because the SBP increased
(<130, 130-140, and >=140 mmHg: 1.0, 1.3, and 2.3, respectively; P = 0.045);
however, median proteinuria was comparable in patients without hyalinosis (n =
50), regardless of SBP. Multiple logistic analysis revealed that combined high BP
and hyalinosis were significantly associated with increased proteinuria, defined
as equal to or greater than the median value (odds ratio: 5.99, 95% confidence
interval: 1.13-31.70, P < 0.05 vs. high BP-/hyalinosis-). Moreover, this
combination was associated with the largest glomerular diameter. CONCLUSION:
Renal arteriolar hyalinosis may potentiate susceptibility to BP-related
glomerular damage in patients with nonnephrotic CKD. Dysregulated afferent
arteriolar resistance via arteriolar sclerosis may affect hypertensive renal
damage.
PMID- 27607460
TI - Vascular stiffness determined from a nocturnal digital pulse wave signal:
association with sleep, sleep-disordered breathing, and hypertension.
AB - OBJECTIVES: Reflection of the finger pulse wave form is a valid measure of
arterial stiffness, which may be continuously assessed during sleep. We
investigated the relationships between sleep, sleep-disordered breathing,
hypertension, and pulse propagation time (PPT) in patients with suspected sleep
apnea. METHODS: The digital photoplethysmographic signal derived from finger
pulse oximetry was recorded during overnight sleep studies in 440 patients (64%
men, age 55 +/- 12 years, BMI 30 +/- 6 kg/m, apnea-hypopnea index 19 +/- 19 n/h).
PPT, defined as the time interval between the systolic and diastolic peak of the
finger pulse wave, was calculated. The influence of sleep stages on PPT were
assessed in patients undergoing polysomnography. Generalized linear models were
used to study predictors of PPT and hypertension. RESULTS: Mean overnight PPT was
independently associated with age (beta = -1.34, P < 0.001), height (beta = 0.47,
P = 0.047), history of smoking (beta = -9.44, P = 0.005), and apnea-hypopnea
index (beta = -0.18, P = 0.043). PPT was shorter in hypertensive patients
compared with normotensive patients (160 +/- 33 vs. 177 +/- 47 ms, P < 0.001) and
independently associated with a diagnosis of hypertension (P = 0.043). PPT was
influenced by sleep stage (highest PPT during slow wave sleep compared with wake
and all other sleep stages, all P < 0.001) and varied across sleep apnea severity
groups in normotensive but not in hypertensive patients (P = 0.028 and 0.64,
respectively). CONCLUSION: Overnight PPT by oximetry was strongly associated with
factors known to determine daytime vascular stiffness. In addition, PTT provides
information on functional and structural vascular properties during sleep. This
novel technique offers new opportunities to noninvasively monitor vascular
function during the sleeping period.
PMID- 27607462
TI - Guidelines for primary aldosteronism: uptake by primary care physicians in
Europe.
AB - CONTEXT: Primary aldosteronism is the most frequent form of secondary
hypertension but is still markedly underdiagnosed. In 2008, the Endocrine Society
released guidelines for primary aldosteronism diagnosis and management; current
indications are that they are not being widely followed. OBJECTIVE: To
investigate the level of knowledge and application of the guidelines in a large
representative cohort of general practitioners (GPs) in Italy and Germany.
SETTING AND DESIGN: The study was carried out by web questionnaire on
hypertension and primary aldosteronism management with 500 GPs (250 in Italy and
250 in Germany), stratified by geographical area and city size. RESULTS: The mean
number of patients seen was 1747 (Germany) and 1388 (Italy). Of these, 18% were
diagnosed as hypertensive in Italy and 25% in Germany. Renin and aldosterone
measurements were ordered by 7% of GPs in Italy and 8% in Germany. GPs in Italy
considered 8% of patients eligible for aldosterone and renin measurements
compared with 13% of GPs in Germany. In Italy, primary aldosteronism prevalence
was 1% among hypertensive patients; 36% of the GPs reported no primary
aldosteronism patients under their care or diagnosed previously. In Germany, the
prevalence of primary aldosteronism was 2% among hypertensive patients; 19% of
GPs had no primary aldosteronism patients. CONCLUSION: In Germany and in Italy,
primary aldosteronism is not widely recognized by GPs; Endocrine Society
guidelines for primary aldosteronism diagnosis are not well known or applied,
resulting in marked underdiagnosis of the disease.
PMID- 27607461
TI - Xanthine oxidase gene variants and their association with blood pressure and
incident hypertension: a population study.
AB - OBJECTIVE: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the
terminal steps of the purine metabolism; meanwhile reactive oxygen species are
formed. We hypothesized that uric acid production, as assessed indirectly from
XOR variants, is associated with hypertension. METHODS: Among 2769 participants
(48.3% men; mean age 40.7 years) randomly recruited from European populations, we
genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and
follow-up (median 8.8 years). The relation between variants of the XOR gene with
changes in pulse pressure and mean arterial pressure over time; and incidence of
hypertension, were analyzed. RESULTS: Compared with nonminor allele carriers,
pulse pressure increased approximately 2 mmHg more in minor allele carriers of
rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased
approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In
2050, participants normotensive at baseline, hazard ratios contrasting risk of
hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95%
confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11
2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false
discovery rate set at 0.25, the aforementioned associations retained
significance. The changes in SBP from baseline to follow-up and the serum levels
of uric acid at baseline (n = 1949) were not associated with XOR. CONCLUSION:
Pending confirmation, our findings suggest that variation in uric acid
production, as captured by genetic variation in XOR, might be a predictor of
changes in BP and in the risk of hypertension.
PMID- 27607463
TI - Intraocular Pressure during Continuous Positive Airway Pressure.
PMID- 27607464
TI - Complementary and Alternative Medicine Use Among Chronically Ill Adolescents from
2 German Birth Cohorts.
AB - BACKGROUND: Pediatric use of complementary and alternative medicine (CAM) is
popular in Europe, and utilization may be even more prevalent in chronically ill
children/adolescents. This study's aim is to assess CAM use among adolescents
with chronic conditions. METHODS: Data on drug utilization (past 4 weeks) and
consultation with CAM providers (past year) were collected using a self
administered questionnaire from 4,677 adolescents from the German
GINIplus/LISAplus birth cohorts. All reported drugs were classified into
therapeutic categories (conventional drugs, homeopathy, herbal drugs, etc.).
Additionally, participants were asked to list any chronic diseases (that were
parent-reported, physician-verified diagnoses such as allergies, atopic
dermatitis, asthma, or other chronic diseases) that they had had over the
previous 5 years. RESULTS: Compared with the total sample, drug utilization in
general (60.1% vs. 41.1%), homeopathy use (11.1% vs. 8.1%), and consultation with
CAM providers (16.9% vs. 10.9%) was significantly more prevalent among
chronically ill adolescents. However, chronically ill adolescents used relatively
(proportion of the defined therapeutic category among all drugs used) more
conventional drugs than healthy adolescents. CONCLUSION: Compared with healthy
adolescents, CAM use is more prevalent among adolescents with chronic conditions.
Nevertheless, CAM may predominantly be used as a complementary treatment option
rather than substituting conventional drugs.
PMID- 27607466
TI - Effects of Different Substrates on Lignocellulosic Enzyme Expression, Enzyme
Activity, Substrate Utilization and Biological Efficiency of Pleurotus Eryngii.
AB - BACKGROUND/AIMS: Pleurotus eryngii is one of the most valued and delicious
mushrooms which are commercially cultivated on various agro-wastes. How different
substrates affect lignocellulosic biomass degradation, lignocellulosic enzyme
production and biological efficiency in Pleurotus eryngii was unclear. METHODS
AND RESULTS: In this report, Pleurotus eryngii was cultivated in substrates
including ramie stalks, kenaf stalks, cottonseed hulls and bulrush stalks. The
results showed that ramie stalks and kenaf stalks were found to best suitable to
cultivate Pleurotus eryngii with the biological efficiency achieved at 55% and
57%, respectively. In order to establish correlations between different
substrates and lignocellulosic enzymes expression, the extracellular proteins
from four substrates were profiled with high throughput TMT-based quantitative
proteomic approach. 241 non-redundant proteins were identified and 74 high
confidence lignocellulosic enzymes were quantified. Most of the cellulases,
hemicellulases and lignin depolymerization enzymes were highly up-regulated when
ramie stalks and kenaf stalks were used as carbon sources. The enzyme activities
results suggested cellulases, hemicellulases and lignin depolymerization enzymes
were significantly induced by ramie stalks and kenaf stalks. CONCLUSION: The
lignocelluloses degradation, most of the lignocellulosic enzymes expressions and
activities of Pleurotus eryngii had positive correlation with the biological
efficiency, which depend on the nature of lignocellulosic substrates. In
addition, the lignocellulosic enzymes expression profiles during Pleurotus
eryngii growth in different substrates were obtained. The present study suggested
that most of the lignocellulosic enzymes expressions and activities can be used
as tools for selecting better performing substrates for commercial mushroom
cultivation.
PMID- 27607465
TI - Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia
on Needle Biopsy.
AB - Importance: Atypical ductal hyperplasia (ADH) is a known risk factor for breast
cancer. Published risk estimates are based on cohorts that included women whose
ADH was diagnosed before widespread use of screening mammograms and did not
differentiate between the methods used to diagnose ADH, which may be related to
the size of the ADH focus. These risks may overestimate the risk in women with
presently diagnosed ADH. Objective: To examine the risk of invasive cancer
associated with ADH diagnosed using core needle biopsy vs excisional biopsy.
Design: A cohort study was conducted comparing the 10-year cumulative risk of
invasive breast cancer in 955 331 women undergoing mammography with and without a
diagnosis of ADH. Data were obtained from 5 breast imaging registries that
participate in the National Cancer Institute-funded Breast Cancer Surveillance
Consortium. Exposures: Diagnosis of ADH on core needle biopsy or excisional
biopsy in women undergoing mammography. Main Outcomes and Measures: Ten-year
cumulative risk of invasive breast cancer. Results: The sample included 955 331
women with 1727 diagnoses of ADH, 1058 (61.3%) of which were diagnosed by core
biopsy and 635 (36.8%) by excisional biopsy. The mean (interquartile range) age
of the women at diagnosis was 52.6 (46.9-60.4) years. From 1996 to 2012, the
proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten
years following a diagnosis of ADH, the cumulative risk of invasive breast cancer
was 2.6 (95% CI, 2.0-3.4) times higher than the risk in women with no ADH.
Atypical ductal hyperplasia diagnosed via excisional biopsy was associated with
an adjusted hazard ratio (HR) of 3.0 (95% CI, 2-4.5) and, via core needle biopsy,
with an adjusted HR of 2.2 (95% CI, 1.5-3.4). Ten years after an ADH diagnosis,
an estimated 5.7% (95% CI, 4.3%-10.1%) of the women had a diagnosis of invasive
cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk
(6.7%; 95% CI, 3.0%-12.8%) compared with those with ADH diagnosed via core needle
biopsy (5%; 95% CI, 2.2%-8.9%). Conclusions and Relevance: Current 10-year risks
of invasive breast cancer after a diagnosis of ADH may be lower than those
previously reported. The risk associated with ADH is slightly lower for women
whose ADH was diagnosed by needle core biopsy compared with excisional biopsy.
PMID- 27607467
TI - Overexpression of Catalase Enhances Benzo(a)pyrene Detoxification in Endothelial
Microsomes.
AB - We previously reported that overexpression of catalase upregulated xenobiotic-
metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP)
intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic
reticulum (ER) is the most active organelle involved in BaP metabolism. To
examine the involvement of ER in catalase-induced BaP detoxification, we compared
the level and distribution of XMEs, and the profile of BaP intermediates in the
microsomes of wild-type and catalase transgenic endothelial cells. Our data
showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1,
CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of
NAD(P)H: quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP).
Treatment of wild-type MAECs with 1MUM BaP for 2 h increased the expression of
microsomal CYP1A1, 1B1 and NQO1 by ~300, 64 and 116%, respectively. However, the
same treatment did not significantly alter the expression of EH1 and GSTP.
Overexpression of catalase did not significantly increase EH1, but upregulated
BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following
order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the
distribution of each of these enzymes in the microsomes. In contrast to our
previous report showing lower level of BaP phenols versus BaP diols/diones in the
whole-cell, this report demonstrated that the sum of microsomal BaP phenolic
metabolites were ~60% greater than that of the BaP diols/diones after exposure of
microsomes to BaP. Overexpression of catalase reduced the concentrations of
microsomal BaP phenols and diols/diones by ~45 and 95%, respectively. This
process enhanced the ratio of BaP phenol versus diol/dione metabolites in a
potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins,
but not EH1 in the ER might be the mechanism by which overexpression of catalase
reduces the levels of all the BaP metabolites, and enhances the ratio of BaP
phenolic metabolites versus diol/diones in endothelial microsomes.
PMID- 27607468
TI - A Bayesian framework for joint morphometry of surface and curve meshes in multi
object complexes.
AB - We present a Bayesian framework for atlas construction of multi-object shape
complexes comprised of both surface and curve meshes. It is general and can be
applied to any parametric deformation framework and to all shape models with
which it is possible to define probability density functions (PDF). Here, both
curve and surface meshes are modelled as Gaussian random varifolds, using a
finite-dimensional approximation space on which PDFs can be defined. Using this
framework, we can automatically estimate the parameters balancing data-terms and
deformation regularity, which previously required user tuning. Moreover, it is
also possible to estimate a well-conditioned covariance matrix of the deformation
parameters. We also extend the proposed framework to data-sets with multiple
group labels. Groups share the same template and their deformation parameters are
modelled with different distributions. We can statistically compare the
groups'distributions since they are defined on the same space. We test our
algorithm on 20 Gilles de la Tourette patients and 20 control subjects, using
three sub-cortical regions and their incident white matter fiber bundles. We
compare their morphological characteristics and variations using a single
diffeomorphism in the ambient space. The proposed method will be integrated with
the Deformetrica software package, publicly available at www.deformetrica.org.
PMID- 27607469
TI - Random forest regression for magnetic resonance image synthesis.
AB - By choosing different pulse sequences and their parameters, magnetic resonance
imaging (MRI) can generate a large variety of tissue contrasts. This very
flexibility, however, can yield inconsistencies with MRI acquisitions across
datasets or scanning sessions that can in turn cause inconsistent automated image
analysis. Although image synthesis of MR images has been shown to be helpful in
addressing this problem, an inability to synthesize both T2-weighted brain images
that include the skull and FLuid Attenuated Inversion Recovery (FLAIR) images has
been reported. The method described herein, called REPLICA, addresses these
limitations. REPLICA is a supervised random forest image synthesis approach that
learns a nonlinear regression to predict intensities of alternate tissue
contrasts given specific input tissue contrasts. Experimental results include
direct image comparisons between synthetic and real images, results from image
analysis tasks on both synthetic and real images, and comparison against other
state-of-the-art image synthesis methods. REPLICA is computationally fast, and is
shown to be comparable to other methods on tasks they are able to perform.
Additionally REPLICA has the capability to synthesize both T2-weighted images of
the full head and FLAIR images, and perform intensity standardization between
different imaging datasets.
PMID- 27607471
TI - A multicentre phase II trial of cabazitaxel in patients with advanced non-small
cell lung cancer progressing after docetaxel-based chemotherapy.
AB - BACKGROUND: Cabazitaxel, a semisynthetic microtubule inhibitor, has shown
antitumour activity in models resistant to paclitaxel and docetaxel, and it has
been approved for the treatment of docetaxel-resistant prostate cancer. We
investigated its activity in patients with advanced non-small-cell lung cancer
(NSCLC) progressing under or after docetaxel-based regimens. METHODS: Patients
with locally advanced unresectable or metastatic NSCLC, with an Eastern
Cooperative Oncology Group performance status of 0-2, were enrolled; patients had
to have received up to two prior chemotherapy regimens for the treatment of
advanced disease, including one docetaxel-containing regimen. Treatment consisted
of cabazitaxel (25 mg m(-2) intravenously, every 21 days) until disease
progression. The primary end point was the overall response rate. RESULTS: Among
the 46 evaluable patients, 28.3% had squamous cell carcinoma and 54.3% had
adenocarcinoma. Eight (17.4%) patients had received one and 38 (82.6%) two prior
chemotherapy regimens. Treatment compliance was 95%; 26 (16%) cycles were delayed
because of toxicity, (n=13) and dose reduction was required in 6 (13%) patients
because of haematologic toxicity. Six (13%) patients achieved a partial response
and 17 (37.0%) stable disease. The median progression-free survival and overall
survival were 2.1 (95% confidence interval (CI): 1.0-3.2) and 7.4 (95% CI: 5.2
9.6) months, respectively. Grade 4 adverse events included neutropenia (n=8;
17%), febrile neutropenia (n=6; 13%) and thrombocytopenia (n=3; 6.5%). There was
one treatment-related death. CONCLUSIONS: Cabazitaxel exhibits activity in NSCLC
patients pre-treated with docetaxel-based chemotherapy with a substantial but
manageable toxicity profile. The drug merits further evaluation in this
indication.
PMID- 27607470
TI - Gene expression profiling identifies distinct molecular subgroups of
leiomyosarcoma with clinical relevance.
AB - BACKGROUND: Soft tissue sarcomas are heterogeneous and a major complication in
their management is that the existing classification scheme is not definitive and
is still evolving. Leiomyosarcomas, a major histologic category of soft tissue
sarcomas, are malignant tumours displaying smooth muscle differentiation.
Although defined as a single group, they exhibit a wide range of clinical
behaviour. We aimed to carry out molecular classification to identify new
molecular subgroups with clinical relevance. METHODS: We used gene expression
profiling on 20 extra-uterine leiomyosarcomas and cross-study analyses for
molecular classification of leiomyosarcomas. Clinical significance of the
subgroupings was investigated. RESULTS: We have identified two distinct molecular
subgroups of leiomyosarcomas. One group was characterised by high expression of
26 genes that included many genes from the sub-classification gene cluster
proposed by Nielsen et al. These sub-classification genes include genes that have
importance structurally, as well as in cell signalling. Notably, we found a
statistically significant association of the subgroupings with tumour grade.
Further refinement led to a group of 15 genes that could recapitulate the tumour
subgroupings in our data set and in a second independent sarcoma set. Remarkably,
cross-study analyses suggested that these molecular subgroups could be found in
four independent data sets, providing strong support for their existence.
CONCLUSIONS: Our study strongly supported the existence of distinct
leiomyosarcoma molecular subgroups, which have clinical association with tumour
grade. Our findings will aid in advancing the classification of leiomyosarcomas
and lead to more individualised and better management of the disease.
PMID- 27607473
TI - Determination of genotoxic effects of methidathion alkaline hydrolysis in human
lymphocytes using the micronucleus assay and square-wave voltammetry.
AB - The interaction of pesticides with environmental factors, such as pH, may result
in alterations of their physicochemical properties and should be taken into
consideration in regard to their classification. This study investigates the
genotoxicity of methidathion and its alkaline hydrolysis by-products in cultured
human lymphocytes, using the square-wave voltammetry (square wave-adsorptive
cathodic stripping voltammetry (SW-AdCSV) technique) and the cytokinesis block
micronucleus assay (CBMN assay). According to the SW-AdCSV data the alkaline
hydrolysis of methidathion results in two new molecules, one non-electro-active
and a second electro-active which is more genotoxic than methidathion itself in
cultured human lymphocytes, inducing higher micronuclei frequencies. The present
study confirms the SW-AdCSV technique as a voltammetric method which can
successfully simulates the electrodynamics of the cellular membrane.
PMID- 27607472
TI - Aberrant Epigenetic Regulation in the Pathogenesis of Systemic Lupus
Erythematosus and Its Implication in Precision Medicine.
AB - Great progress has been made in the last decades in understanding the complex
immune dysregulation in systemic lupus erythematosus (SLE), yet the efforts to
pursue an effective treatment of SLE proved to be futile. The pathoetiology of
SLE involves extremely complicated and multifactorial interaction among various
genetic and epigenetic factors. Multiple gene loci predispose to disease
susceptibility, and the interaction with epigenetic modifications mediated
through sex, hormones, and the hypothalamo-pituitary-adrenal axis complicates
susceptibility and manifestations of this disease. Finally, certain environmental
and psychological factors probably trigger the disease via epigenetic mechanisms.
In this review, we summarize and discuss recent epigenetic studies of SLE and
suggest a personalized approach to the dissection of disease onset and therapy or
precision medicine. We speculate that in the future, precision medicine based on
epigenetic and genetic information could help guide more effective targeted
therapeutic intervention.
PMID- 27607474
TI - Baseline Pulse Pressure, Acute Kidney Injury, and Mortality After Noncardiac
Surgery.
AB - BACKGROUND: Increased pulse pressure (PP) is an important independent predictor
of cardiovascular outcome and acute kidney injury (AKI) after cardiac surgery.
The objective of this study was to determine whether elevated baseline PP is
associated with postoperative AKI and 30-day mortality after noncardiac surgery.
METHODS: We evaluated 9125 adult patients who underwent noncardiac surgery at
Duke University Medical Center between January 2006 and December 2009. Baseline
arterial blood pressure was defined as the mean of the first 5 measurements
recorded by the automated record keeping system before inducing anesthesia.
Multivariable logistic regression analysis was performed to determine whether
baseline PP adjusted for other perioperative risk factors was independently
associated with postoperative AKI and 30-day mortality. RESULTS: Of the 9125
patients, the baseline PP was <40 mm Hg in 1426 (15.6%), 40-80 mm Hg in 6926
(75.9%), and >80 mm Hg in 773 (8.5%) patients. The incidence of AKI was 19.8%,
which included 8.4% (151 patients) and 4.2% (76 patients) who experienced stage
II and III AKI, respectively. In the risk-adjusted model for postoperative AKI,
elevated baseline PP was associated with higher odds for postoperative AKI
(adjusted odds ratio [OR] for every 20 mm Hg increase in PP, 1.17; 95% confidence
interval [CI], 1.10-1.25; P < .0001). Also elevated baseline preoperative PP was
significantly associated with mild (stage I; OR, 1.19; 95% CI, 1.11-1.27; P <
.0001), but not with more advanced stages of postoperative AKI or with an
incremental risk for 30-day mortality. CONCLUSIONS: We found a significant
association between elevated baseline PP and postoperative AKI in patients who
underwent noncardiac surgery. However, elevated PP was not significantly
associated with more advanced stages of postoperative AKI or 30-day mortality in
these patients.
PMID- 27607477
TI - Structural Integrity of a Simple Method to Repair Disrupted Tracheal Tube Pilot
Balloon Assemblies.
AB - BACKGROUND: An intact pilot balloon assembly is crucial to the proper function of
a cuffed tracheal tube. Disruption of the pilot balloon, transection of the
inflation line, or valve incompetence results in cuff deflation, which may lead
to inadequate ventilation and aspiration of secretions. Such failures typically
result in tracheal tube replacement, but this may be a safety risk if a difficult
reintubation is anticipated. We recently encountered such a patient who remained
intubated postoperatively and in whom the inflation line was transected, causing
a large leak. We describe a method to reconstitute the inflation line and report
on the structural integrity of the repair. We hypothesized that the repaired
assembly would maintain cuff pressure not statistically different from an intact
device, but that the inflation line would be weaker. METHODS: The distal
(tapered) portion of a 22-gauge intravenous (IV) catheter was partially inserted
into the severed end of the inflation line. A new pilot balloon was cut from an
intact tracheal tube with the tubing attached, the end of which had been dilated
using a 22-gauge IV catheter. The new tubing was then guided over the protruding
portion of the catheter, creating an internal stent. We measured the drop in cuff
pressure after 8 hours in an artificial trachea for repaired and intact tracheal
tubes. We tested the integrity of the repaired segments, underwater, to high
pressure inflation. We measured the static tensile strength of the inflation line
from intact and repaired tracheal tubes. Data are presented as the mean +/-
standard error. Differences were assessed using the unpaired, 2-sided Student t
test, with P < .05 required to claim statistical significance. RESULTS: Eight
hour interval measurements in 10 intact versus 10 repaired tracheal tubes
demonstrated no significant difference in pressure drop (mean difference = 0.5 cm
H2O; 95% confidence interval, -2.2 to 1.2 cm H2O; P = .54). There was no visible
air leak from 10 repaired inflation line segments when the cuff was inflated to
120 mm Hg. The force needed to break the repaired inflation line was lower than
for the intact tubing (n = 7 of each; mean difference = -21.9 N; 95% confidence
interval, -25.7 to -18.1 N; P < 10). Repairs to tracheal tubes from various
manufacturers with inner diameters ranging from 3.0 to 8.0 mm were successful.
CONCLUSIONS: Repairing a disrupted pilot balloon assembly using an IV catheter as
a stent inside the inflation line is an effective temporizing measure in
situations where ventilation is impaired and where tracheal tube replacement may
present an excessive patient risk.
PMID- 27607476
TI - Long-Acting Patient-Controlled Opioids Are Not Associated With More Postoperative
Hypoxemia Than Short-Acting Patient-Controlled Opioids After Noncardiac Surgery:
A Cohort Analysis.
AB - BACKGROUND: Opioids can contribute to postoperative desaturation. Short-acting
opioids, titrated to need, may cause less desaturation than longer-acting
opioids. We thus tested the primary hypothesis that long-acting patient
controlled intravenous opioids are associated with more hypoxemia (defined as an
integrated area under a postoperative oxyhemoglobin saturation of 95%) than short
acting opioids. METHODS: This analysis was a substudy of VISION, a prospective
cohort study focused on perioperative cardiovascular events (NCT00512109). After
excluding for predefined criteria, 191 patients were included in our final
analysis, with 75 (39%) patients being given fentanyl (short-acting opioid group)
and 116 (61%) patients being given morphine and/or hydromorphone (long-acting
opioid group). The difference in the median areas under a postoperative
oxyhemoglobin saturation of 95% between short-acting and long-acting opioids was
compared using multivariable median quantile regression. RESULTS: The short
acting opioid median area under a postoperative oxyhemoglobin saturation of 95%
per hour was 1.08 (q1, q3: 0.62, 2.26) %-h, whereas the long-acting opioid median
was 1.28 (0.50, 2.23) %-h. No significant association was detected between long
acting and short-acting opioids and median area under a postoperative
oxyhemoglobin saturation of 95% per hour (P = .66) with estimated change in the
medians of -0.14 (95% CI, -0.75, 0.47) %-h for the patients given long-acting
versus short-acting IV patient-controlled analgesia opioids. CONCLUSIONS: Long
acting patient-controlled opioids were not associated with the increased
hypoxemia during the first 2 postoperative days.
PMID- 27607478
TI - Abnormalities of Mitral Subvalvular Apparatus in Hypertrophic Cardiomyopathy:
Role of Intraoperative 3D Transesophageal Echocardiography.
PMID- 27607479
TI - US National Anesthesia Workload on Saturday and Sunday Mornings.
AB - BACKGROUND: In order to provide guidance to organizations considering elective
weekend surgical case scheduling, we analyzed data from the American Society of
Anesthesiologist's Anesthesia Quality Institute. We determined the US anesthesia
workload on Saturdays and Sundays. METHODS: The American Society of
Anesthesiologist's Anesthesia Quality Institute data were from all US anesthesia
groups that submitted cases to the National Anesthesia Clinical Outcomes Registry
for 2013. For each of the N = 2,075,188 cases, we identified the local date and
time of the start of anesthesia care and the duration of anesthesia care.
Anesthesia workload was measured as the time from the start to the end of
continuous anesthesia care. Because elective cases are rarely scheduled on
Sundays, we considered the difference in workload between Saturday and Sunday to
estimate elective case scheduling. This difference would be an overestimate if
some patients' scheduled cases were postponed from Friday to Saturday. Data are
reported as mean +/- standard error; N = 13 four-week periods. RESULTS: The
difference in the anesthesia minutes between Saturdays versus Sundays 7:00 AM to
2:59 PM (ie, elective caseload) represented just 0.38% +/- 0.02% of the total
minutes nationwide; Saturday 1.57% +/- 0.03% versus Sunday 1.19% +/- 0.02%. The P
< .00001 comparing the 0.38% with 1.0% and, also, with 0.5% (upper 99% confidence
interval = 0.42%). CONCLUSIONS: The imputed Saturday elective schedule represents
a tiny percentage of overall anesthetic workload nationwide. Saturday elective
surgery is currently an uncommon practice in the United States. Based on this
prior knowledge, organizations considering changes to their current scheduling
strategies should perform a thorough statistical analysis of their local workload
prior to implementation and apply evidence-based criteria to guide their decision
making process.
PMID- 27607480
TI - Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury.
AB - BACKGROUND: Superoxide, nitric oxide (NO), and peroxynitrite are important
mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the
renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N
nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4
pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide,
NO, and peroxynitrite, respectively. METHODS: Male Sprague-Dawley rats were
randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated
group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour
reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP,
respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood
urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase,
histological changes, apoptosis, and monocyte infiltration were evaluated. In
addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in
a second independent experiment. RESULTS: The administration of ALP, L-NAME, and
FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for
ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the
histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP
attenuated the oxidative stress response as determined by a decrease in
malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P =
.0066 for all), and monocyte infiltration (P = .0066 for all). The combined
treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than
FeTMPyP (P = .016 for Cr; P = .0079 for BUN). CONCLUSIONS: Superoxide, NO, and
peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite
formation, via inhibition of superoxide or NO, or the induction of peroxynitrite
decomposition may be beneficial in renal I/R injury.
PMID- 27607481
TI - Revision of the genus Verilus (Perciformes: Acropomatidae) with a description of
a new species.
AB - The acropomatid genus Verilus is redescribed as a senior synonym of Apogonops and
Neoscombrops with description of a new species and a taxonomic revision of the
five species that were formerly classified in these genera. This genus is
characterized by the following combination of characters: a canine tooth (rarely
two) near symphysis of premaxilla of upper jaw but lacking a row of conical teeth
on anterior part of outer premaxillary margin; a canine tooth (rarely two) near
symphysis of dentary with only villiform or a row of conical teeth posteriorly;
three anal-fin spines; 10 dorsal-fin spines; pelvic-fin spine smooth; luminous
organ absent. This genus comprises six species: Verilus sordidus (type species,
western Atlantic Ocean); Verilus anomalus (off southern and eastern coast of
Australia); Verilus atlanticus (western Atlantic Ocean); Verilus cynodon (south
western Indian Ocean); Verilus pacificus (north-western and central Pacific
Ocean); Verilus starnesi sp. nov. (Coral Sea off Chesterfield Islands, New
Caledonia). These species are distinguishable from one another by dentition on
the lower jaw, numbers of pectoral-fin rays, gill rakers and lateral-line scales,
features of the proximal-middle radial of the first anal-fin pterygiophore,
presence or absence of basioccipital fossa and body depth.
PMID- 27607482
TI - Persistent grunting respirations after birth.
AB - BACKGROUND: Grunting respirations occurring in the first hours of life is a
frequent nonspecific clinical sign. Our objective was to assess the clinical
significance of grunting lasting over two hours of birth in term and near term
newborns. METHODS: A five years retrospective study of all newborns >=35+0 weeks
of gestational age admitted for grunting to a level III Neonatal Intensive Care
Unit (NICU). RESULTS: Prolonged grunting occurred in 1.2% of the delivered
newborns. Data on 151 grunter newborns and 302 controls were reviewed. Higher
mother's age, pregnancy complications, lower gestational age, male gender,
resuscitation need at birth, respiratory signs and therapy were associated to
prolonged grunting. Poor adaptation to extrauterine life was the most frequent
cause of grunting occurring in 73 (48.3%) of the cases, followed by transient
tachypnea of the newborn (40 cases, 26.5%); RDS (7 cases, 4.6%) and infection
(sepsis and pneumonia, 7 cases, 4.6%). Less common causes were: birth trauma (4
cases, 2.6%); pneumomediastinum (4 cases, 2.6%); hypoxic-ischemic encephalopathy
(2 cases, 1.3%); polycythemia (1 case, 0.6%); anemia (1 case; 0.6%); meconium
aspiration (1 case, 0.6%); congenital heart defect (1 case, 0.6%); congenital
diaphragmatic hernia (1 case; 0.6%); malformation of the nose (1 case;0.6%); and
immature teratoma of the thymus (1 case, 0.6%). Complications occurred in two
patients (pneumothorax=1; pneumomediastinum=1). No mortality was observed. NICU
stay was 5 days (1-23) CONCLUSIONS: Although persistent grunting respirations
after birth follow a benign course in the majority, all affected term and near
term newborns should be carefully observed and treated.
PMID- 27607484
TI - Low-reflection region within the stop band of a finite or absorbing periodic
multilayer.
AB - Nonabsorbing periodic multilayers reflect both the s(TE) and p(TM) polarizations
strongly within the respective stop bands. We find that finite or weakly
absorbing layers, for which the reflection is usually strong within the stop
bands, can have zero or very weak reflection of the p polarization near the
middle of the stop band, close to glancing incidence. Approximate expressions are
derived for the location (in angle of incidence and frequency) of the reflection
minimum and compared with calculated reflectances for specific multilayers.
PMID- 27607483
TI - Can clinical characteristics be criteria to perform chromosomal microarray
analysis in children and adolescents with autism spectrum disorders?
AB - BACKGROUND: Chromosomal microarray analysis (CMA) has become increasingly
important in the assessment of patients with autism spectrum disorders (ASD), but
is sometimes restricted to patients with specific additional characteristics or
comorbidities. We aim to evaluate whether certain clinical characteristics could
be criteria to perform CMA and also to investigate the diagnostic value of CMA
compared to other genetic analyses in our patient population. METHODS: The files
of 311 children diagnosed with ASD were retrospectively analyzed. The retrieved
clinical characteristics included: intellectual disability, major congenital
anomalies, epilepsy, prematurity, familial history of ASD,
electroencephalography, and brain MRI findings. Results of the genetic analyses,
including CMA, were collected and statistical analysis was performed. RESULTS:
CMA was performed in 79 patients and was found to be normal in 55 (group 1) and
abnormal in 23 children (group 2). We found no statistically significant
difference between groups in the presence of the clinical characteristics. The
diagnostic yield of CMA (8.9%) was higher than in conventional karyotyping (1.6%)
and other genetic analyses (3.8%). CONCLUSIONS: In our study, there was no
significant difference in the presence of clinical characteristics in patients
diagnosed with ASD who had abnormal CMA results compared to patients with normal
CMA results. Therefore, the presence of these characteristics should not be used
as criteria to perform CMA. Secondly, the diagnostic yield of CMA is higher than
that of other genetic analyses. Our study supports the general recommendation
that CMA should be offered as a first-tier test in the assessment of patients
with ASD.
PMID- 27607485
TI - Determination of the complex refractive index of a subwavelength-diameter
platinum or gold pipe by light scattering.
AB - The complex refractive indices of Pt and Au pipes that are subwavelength in
diameter have been found to be different from those of metal thin films for the
first time. The metal pipe is made from a spider silk of half-wavelength diameter
clad with Pt or Au and illuminated by a plane-polarized laser of wavelength 660
nm at normal incidence. The angular distribution of the light intensity scattered
by the pipe is measured and fitted using theoretical calculations based on the
corresponding model. The fitting results have lead to the optimum values and
uncertainty ranges of the indices and the diameter of the pipe. A field emission
scanning electron microscope confirms the diameter from the optical estimation
and reveals an image of the surface of the pipe.
PMID- 27607486
TI - Reverse propagation and negative angular momentum density flux of an optical
nondiffracting nonparaxial fractional Bessel vortex beam of progressive waves.
AB - Energy and angular momentum flux density characteristics of an optical
nondiffracting nonparaxial vector Bessel vortex beam of fractional order are
examined based on the dual-field method for the generation of symmetric electric
and magnetic fields. Should some conditions determined by the polarization state,
the half-cone angle as well as the beam-order (or topological charge) be met, the
axial energy and angular momentum flux densities vanish (representing Poynting
singularities), before they become negative. These negative counterintuitive
properties suggest retrograde (negative) propagation as well as a rotation
reversal of the angular momentum with respect to the beam handedness. These
characteristics of nondiffracting nonparaxial Bessel fractional vortex beams of
progressive waves open new capabilities in optical tractor beam tweezers, optical
spanners, invisibility cloaks, optically engineered metamaterials, and other
applications.
PMID- 27607487
TI - Wideband image demodulation via bi-dimensional multirate frequency
transformations.
AB - Existing image demodulation approaches based on the two-dimensional (2D)
multicomponent AM-FM model assume narrowband components that can be demodulated
using energy operators, Hilbert transforms, or the monogenic image approaches.
However, if the FM components are wideband, then these demodulation approaches
incur significant errors. Recent work by the authors extended wideband FM
demodulation in one dimension to accommodate large conversion factors using
multirate frequency transformations. In this paper, we extend the multirate
frequency transformations technique developed for one-dimensional signals to 2D
and images in conjunction with a recently proposed 2D higher-order energy
demodulation approach. This extension is applied to both synthetic and real
images to demonstrate the efficacy of the approach.
PMID- 27607488
TI - Polynomial modal analysis of lamellar diffraction gratings in conical mounting.
AB - An efficient numerical modal method for modeling a lamellar grating in conical
mounting is presented. Within each region of the grating, the electromagnetic
field is expanded onto Legendre polynomials, which allows us to enforce in an
exact manner the boundary conditions that determine the eigensolutions. Our code
is successfully validated by comparison with results obtained with the analytical
modal method.
PMID- 27607489
TI - Infrared refractive index dispersion of polymethyl methacrylate spheres from Mie
ripples in Fourier-transform infrared microscopy extinction spectra.
AB - We performed high-resolution Fourier-transform infrared (FTIR) spectroscopy of a
polymethyl methacrylate (PMMA) sphere of unknown size in the Mie scattering
region. Apart from a slow, oscillatory structure (wiggles), which is due to an
interference effect, the measured FTIR extinction spectrum exhibits a ripple
structure, which is due to electromagnetic resonances. We fully characterize the
underlying electromagnetic mode structure of the spectrum by assigning mode
numbers to each of the ripples in the measured spectrum. We show that analyzing
the ripple structure in the spectrum in the wavenumber region from about 3000
cm-1 to 8000 cm-1 allows us to determine both the unknown
radius of the sphere and the PMMA index of refraction, which shows a strong
frequency dependence in this infrared spectral region. While in this paper we
focus on examining a PMMA sphere as an example, our method of determining the
refractive index and its dispersion from infrared extinction spectra is generally
applicable for the determination of the index of refraction of any transparent
substance that can be shaped into micron-sized spheres.
PMID- 27607490
TI - Characteristics of surface plasmon-polariton waves excited on 2D periodically
patterned columnar thin films of silver.
AB - Periodically patterned thin films of slanted silver nanocolumns were deposited by
directing a collimated vapor flux of silver toward square and hexagonal gratings
of photoresist on glass substrates. Angle-resolved specular-transmittance
measurements in the visible and near-infrared wavelength bands on these
periodically patterned columnar thin films (CTFs) were carried out to investigate
the excitation of surface plasmon-polariton (SPP) waves bound tightly to either
the air/CTF or the photoresist/CTF interfaces. The orientation of the propagation
vector of the incident p-polarized plane wave with respect to the morphologically
significant plane of the CTFs was varied to reveal asymmetric (unidirectional)
coupling of Floquet modes to SPP waves. The asymmetric coupling is maximal when
the propagation vector of the incident plane wave lies wholly in the
morphologically significant plane. Theoretical understanding based on the
Bruggeman formalism to homogenize the silver CTFs into hyperbolic biaxial
continua is able to explain the experimental observations very well.
PMID- 27607491
TI - Numerical generation of a polarization singularity array with modulated amplitude
and phase.
AB - A point having no defined polarized ellipse azimuthal angle (circularly
polarized) in a space-variant vector field is called a polarization singularity,
and it has three types: Lemon, Monstar, and Star. Recently, the connection of
polarization singularities has been performed. Inspired by this, we conduct a
numerical generation of a polarization singularity array. Our method is based on
two orthogonal linearly polarized light beams with modulated amplitude and phase.
With appropriate distribution functions of amplitudes and phases we can control
the polarized states of polarization singularities, which offer a possibility to
simulate a polarization singularity array.
PMID- 27607492
TI - Three-dimensional inverse problem of geometrical optics: a mathematical
comparison between Fermat's principle and the eikonal equation.
AB - In the framework of geometrical optics, we consider the following inverse
problem: given a two-parameter family of curves (congruence) (i.e.,
f(x,y,z)=c1,g(x,y,z)=c2), construct the refractive-index
distribution function n=n(x,y,z) of a 3D continuous transparent inhomogeneous
isotropic medium, allowing for the creation of the given congruence as a family
of monochromatic light rays. We solve this problem by following two different
procedures: 1. By applying Fermat's principle, we establish a system of two first
order linear nonhomogeneous PDEs in the unique unknown function n=n(x,y,z)
relating the assigned congruence of rays with all possible refractive-index
profiles compatible with this family. Moreover, we furnish analytical proof that
the family of rays must be a normal congruence. 2. By applying the eikonal
equation, we establish a second system of two first-order linear homogeneous PDEs
whose solutions give the equation S(x,y,z)=const. of the geometric wavefronts
and, consequently, all pertinent refractive-index distribution functions
n=n(x,y,z). Finally, we make a comparison between the two procedures described
above, discussing appropriate examples having exact solutions.
PMID- 27607493
TI - Interaction of axial and oblique astigmatism in theoretical and physical eye
models.
AB - The interaction between oblique and axial astigmatism was investigated
analytically (generalized Coddington's equations) and numerically (ray tracing)
for a theoretical eye model with a single refracting surface. A linear vector
summation rule for power vector descriptions of axial and oblique astigmatism was
found to account for their interaction over the central 90 degrees diameter of
the visual field. This linear summation rule was further validated experimentally
using a physical eye model measured with a laboratory scanning aberrometer. We
then used the linear summation rule to evaluate the relative contributions of
axial and oblique astigmatism to the total astigmatism measured across the
central visual field. In the central visual field, axial astigmatism dominates
because the oblique astigmatism is negligible near the optical axis. At
intermediate eccentricities, axial and oblique astigmatism may have equal
magnitude but orthogonal axes, which nullifies total astigmatism at two locations
in the visual field. At more peripheral locations, oblique astigmatism dominates
axial astigmatism, and the axes of total astigmatism become radially oriented,
which is a trait of oblique astigmatism. When eccentricity is specified relative
to a foveal line-of-sight that is displaced from the eye's optical axis,
asymmetries in the visual field map of total astigmatism can be used to locate
the optical axis empirically and to estimate the relative contributions of axial
and oblique astigmatism at any retinal location, including the fovea. We
anticipate the linear summation rule will benefit many topics in vision science
(e.g., peripheral correction, emmetropization, meridional amblyopia) by providing
improved understanding of how axial and oblique astigmatism interact to produce
net astigmatism.
PMID- 27607494
TI - Angular spectral framework to test full corrections of paraxial solutions:
erratum.
AB - In our previous article [J. Opt. Soc. Am. A32, 1236 (2015)JOAOD60740
323210.1364/JOSAA.32.001236] there is an issue concerning the comparison of plane
wave spectrum solutions of paraxial and Helmholtz equations. We compared the
angular plane wave spectrum of Helmholtz solutions with the plane wave spectrum
of the paraxial solutions in terms of normalized projections of paraxial wave
vectors. We show that the proper comparison of plane wave spectra must be done in
terms of angles. The results presented in our previous work are corrected
accordingly. The most important change is that Wunsche's T2 operator
leads to a valid method.
PMID- 27607495
TI - Effects of urban microcellular environments on ray-tracing-based coverage
predictions.
AB - The ray-tracing (RT) algorithm, which is based on geometrical optics and the
uniform theory of diffraction, has become a typical deterministic approach of
studying wave-propagation characteristics. Under urban microcellular
environments, the RT method highly depends on detailed environmental information.
The aim of this paper is to provide help in selecting the appropriate level of
accuracy required in building databases to achieve good tradeoffs between
database costs and prediction accuracy. After familiarization with the operating
procedures of the RT-based prediction model, this study focuses on the effect of
errors in environmental information on prediction results. The environmental
information consists of two parts, namely, geometric and electrical parameters.
The geometric information can be obtained from a digital map of a city. To study
the effects of inaccuracies in geometry information (building layout) on RT-based
coverage prediction, two different artificial erroneous maps are generated based
on the original digital map, and systematic analysis is performed by comparing
the predictions with the erroneous maps and measurements or the predictions with
the original digital map. To make the conclusion more persuasive, the influence
of random errors on RMS delay spread results is investigated. Furthermore, given
the electrical parameters' effect on the accuracy of the predicted results of the
RT model, the dielectric constant and conductivity of building materials are set
with different values. The path loss and RMS delay spread under the same
circumstances are simulated by the RT prediction model.
PMID- 27607496
TI - Transient analysis of electromagnetic wave interactions on plasmonic
nanostructures using a surface integral equation solver.
AB - Transient electromagnetic interactions on plasmonic nanostructures are analyzed
by solving the Poggio-Miller-Chan-Harrington-Wu-Tsai (PMCHWT) surface integral
equation (SIE). Equivalent (unknown) electric and magnetic current densities,
which are introduced on the surfaces of the nanostructures, are expanded using
Rao-Wilton-Glisson and polynomial basis functions in space and time,
respectively. Inserting this expansion into the PMCHWT-SIE and Galerkin testing
the resulting equation at discrete times yield a system of equations that is
solved for the current expansion coefficients by a marching on-in-time (MOT)
scheme. The resulting MOT-PMCHWT-SIE solver calls for computation of additional
convolutions between the temporal basis function and the plasmonic medium's
permittivity and Green function. This computation is carried out with almost no
additional cost and without changing the computational complexity of the solver.
Time-domain samples of the permittivity and the Green function required by these
convolutions are obtained from their frequency-domain samples using a fast
relaxed vector fitting algorithm. Numerical results demonstrate the accuracy and
applicability of the proposed MOT-PMCHWT solver.
PMID- 27607497
TI - Curvatures of the refracted wavefronts and Ronchigrams for a plano arbitrary
lens.
AB - In this work we obtain the equations for curvatures of refracted wavefronts for a
plano arbitrary lens. The functions H0, H1, and
H2 that determine the caustic also determine the curvature of these
wavefronts. The analysis performed in these calculations allows us to study the
behavior of the Ronchigrams for the case of plane incident wavefronts. We apply
this procedure for a plano-spherical lens, and we discover that it is possible to
describe the behavior of the Ronchigrams based on the tau function, which labels
the refracted wavefronts of the optical system.
PMID- 27607498
TI - Spectrum of classes of point emitters of electromagnetic wave fields.
AB - The spectrum of classes of point emitters has been introduced as a numerical tool
suitable for the design, analysis, and synthesis of non-paraxial optical fields
in arbitrary states of spatial coherence. In this paper, the polarization state
of planar electromagnetic wave fields is included in the spectrum of classes,
thus increasing its modeling capabilities. In this context, optical processing is
realized as a filtering on the spectrum of classes of point emitters, performed
by the complex degree of spatial coherence and the two-point correlation of
polarization, which could be implemented dynamically by using programmable
optical devices.
PMID- 27607499
TI - Axial nonimaging characteristics of imaging lenses: erratum.
AB - A correction is provided for the dimension r' in Fig. 12 of J. Opt.
Soc. Am. A33, 970 (2016)1084-752910.1364/JOSAA.33.000970.
PMID- 27607500
TI - Geometrical connection between catacaustics and kinematics of planar motion of a
rigid solid.
AB - Unnoticed and hidden optomechanical analogies between kinematics of planar motion
of a rigid solid and catacaustics generated by mirror reflection on smooth
profiles in geometrical optics are discussed. A concise and self-consistent
theory is developed, which intends to explain and clarify many partial aspects
covered by the literature.
PMID- 27607501
TI - Exponential filtering of singular values improves photoacoustic image
reconstruction.
AB - Model-based image reconstruction techniques yield better quantitative accuracy in
photoacoustic image reconstruction. In this work, an exponential filtering of
singular values was proposed for carrying out the image reconstruction in
photoacoustic tomography. The results were compared with widely popular Tikhonov
regularization, time reversal, and the state of the art least-squares QR-based
reconstruction algorithms for three digital phantom cases with varying signal-to
noise ratios of data. It was shown that exponential filtering provides superior
photoacoustic images of better quantitative accuracy. Moreover, the proposed
filtering approach was observed to be less biased toward the regularization
parameter and did not come with any additional computational burden as it was
implemented within the Tikhonov filtering framework. It was also shown that the
standard Tikhonov filtering becomes an approximation to the proposed exponential
filtering.
PMID- 27607502
TI - Square array of optical vortices generated by multiregion spiral square zone
plate.
AB - Herein, we present a so-called multiregion spiral square zone plate (MRSSZP), in
which a spiral square zone plate is divided into a few regions, so that every
region is composed of Fresnel zones, and the first zone of a given region is the
same as the last zone of the previous region from a transmission point of view.
We show that an MRSSZP can generate unique features of an array of an optical
vortex with topological charge +/-1, so that the number of vortices is directly
related to the number of regions. We also demonstrate that, for an MRSSZP with
topological charge 2, an array of dark cores is formed, which have phase
structures similar to that of the interference of optical vortices with opposite
topological charges. Besides, the focused vortex array follows a modulo-4
transmutation rule. In addition, when the topological charge becomes multiples of
4, an array of focal bright spots surrounded by a dark ring is generated.
Numerical and experimental results verify the superior features of an MRSSZP.
PMID- 27607503
TI - Interactive removal and ground truth for difficult shadow scenes.
AB - A user-centric method for fast, interactive, robust, and high-quality shadow
removal is presented. Our algorithm can perform detection and removal in a range
of difficult cases, such as highly textured and colored shadows. To perform
detection, an on-the-fly learning approach is adopted guided by two rough user
inputs for the pixels of the shadow and the lit area. After detection, shadow
removal is performed by registering the penumbra to a normalized frame, which
allows us efficient estimation of nonuniform shadow illumination changes,
resulting in accurate and robust removal. Another major contribution of this work
is the first validated and multiscene category ground truth for shadow removal
algorithms. This data set containing 186 images eliminates inconsistencies
between shadow and shadow-free images and provides a range of different shadow
types such as soft, textured, colored, and broken shadow. Using this data, the
most thorough comparison of state-of-the-art shadow removal methods to date is
performed, showing our proposed algorithm to outperform the state of the art
across several measures and shadow categories. To complement our data set, an
online shadow removal benchmark website is also presented to encourage future
open comparisons in this challenging field of research.
PMID- 27607504
TI - Optimal configuration of static polarization imagers for target detection:
erratum.
AB - In our recently published article [J. Opt. Soc. Am. A33, 9 (2016)JOAOD60740
323210.1364/JOSAA.33.000009], there was an error of reasoning that changes some
of the results and conclusions, although the key message of the article remains
unaltered. We correct these errors in the present erratum.
PMID- 27607505
TI - Kinematics of illumination patterns and light echoes from flashes.
AB - Flash-induced light echoes-the observation of light reflected from a burst-have
been observed in astronomical settings for more than a century and have been
observed in the laboratory recently. Because of the flight time of light,
perceived light echoes are different from real light illumination patterns on a
scattering plane, neglecting interreflections and non-opaque scattering effects.
The shape and motion of real illumination patterns are studied from a spherical
flash. Then, ellipsoids of constant time delay for a specifically chosen
coordinate system are applied. Generally, perceived light echoes are elliptical
annular rings and the center of a light echo will not start at the flash, which
leads to light echoes moving angularly toward the flash instead of away from it,
a phenomenon actually recorded by other groups. The brightness of perceived light
echoes was studied, and maximum brightness occurred close to the flash's
projective point on the scattering plane. Two specific examples are given and a
magnification effect between perceived echoes and real illumination patterns is
proposed.
PMID- 27607506
TI - Explicit superconic curves.
AB - Conics and Cartesian ovals are extremely important curves in various fields of
science. In addition, aspheric curves based on conics are useful in optical
design. Superconic curves, recently suggested by Greynolds, are extensions of
both conics and Cartesian ovals and have been applied to optical design. However,
they are not extensions of aspheric curves based on conics. In this work, we
investigate another type of superconic curves. These superconic curves are
extensions of not only conics and Cartesian ovals but also aspheric curves based
on conics. Moreover, these are represented in explicit form, while Greynolds's
superconic curves are in implicit form.
PMID- 27607507
TI - Decoherence of orbital angular momentum tangled photons in non-Kolmogorov
turbulence.
AB - Orbital angular momentum (OAM) entangled photons propagating through non
Kolmogorov turbulence are studied by numerical simulations. Here, the paper uses
the multiphase screen model, especially focusing on the influences of the
azimuthal mode and the turbulence parameters (i.e., the generalized exponent, the
outer scale of turbulence, and the inner scale of turbulence) on entanglement
evolution in the weak scintillation regime. The results indicate that the
azimuthal mode, the generalized exponent, and the outer scale of turbulence have
obvious influences on OAM entanglement. However, the influence of the turbulence
inner scale on OAM entanglement can be ignored.
PMID- 27607508
TI - Perfect optical vortex array with controllable diffraction order and topological
charge.
AB - We have demonstrated a holographic grating, the far-field diffraction pattern of
which is a perfect optical vortex (POV) array. The diffraction order, as well as
the topological charge of each spot in the array, is controllable. By setting
different parameters when designing the hologram, the spot in different
diffraction orders will be changed, resulting in the variance of the POV array.
During the experiment, we uploaded holograms of different design on a phase-only
spatial light modulator. We then observed POV arrays with different dimensions
and topological charges using a CCD camera, which fit well with the simulation.
This technique provides the possibility to generate multiple POVs simultaneously,
and can be used in domains where multiple POVs are of high interest such as
orbital angular momentum multiplexed fiber data transmission systems.
PMID- 27607509
TI - Application of derivative matrices of skew rays to design of compound dispersion
prisms.
AB - Numerous optimization methods have been developed in recent decades for optical
system design. However, these methods rely heavily on ray tracing and finite
difference techniques to estimate the derivative matrices of the rays.
Consequently, the accuracy of the results obtained from these methods is
critically dependent on the incremental step size used in the tuning stage. To
overcome this limitation, the present study proposes a comprehensive methodology
for the design of compound dispersion prisms based on the first- and second-order
derivative matrices of skew rays. The proposed method facilitates the analysis
and design of prisms with respect to arbitrary system variables and provides an
ideal basis for automatic prism design applications. Four illustrative examples
are given. It is shown that the optical quantities required to evaluate the prism
performance can be extracted directly from the proposed derivative matrices. In
addition, it is shown in this study that the single-element 3D prism can have the
same deviation angle and spectral dispersion as the 2D compound prism.
PMID- 27607510
TI - Optical properties of V-groove silicon nitride trench waveguides.
AB - We numerically investigate the mode properties of the V-groove silicon nitride
trench waveguides based on the experimental results. The trench waveguides are
suitable for nonlinear applications. By manipulating the waveguide thicknesses,
the waveguides can achieve zero dispersion or a maximized nonlinear parameter of
0.219 W-1.m-1 at 1550 nm. Broadband four-wave mixing with
a gain of 5.545 m-1 is presented as an example. The waveguides can
also be applied in sensing applications with an optimized evanescent intensity
ratio. By etching away the top flat slabs, wider trapezoidal trench waveguides
can be utilized for plasmonic sensing thanks to their TE fundamental modes.
PMID- 27607511
TI - Updated version of an interim connection space LabPQR for spectral color
reproduction: LabLab.
AB - In this paper, we propose a new interim connection space (ICS) called LabLab,
which is an updated version of LabPQR, to overcome the drawback that the last
three dimensions of LabPQR have no definite colorimetric meanings. We extended
and improved the method by which the first three dimensions of LabPQR are deduced
to obtain an ICS consisting of two sets of CIELAB values under different
illuminants, and the reconstructed spectra from LabLab were obtained by
minimizing colorimetric errors by means of the computational formula of the CIE
XYZ tristimulus values combined with least-squares best fit. The improvement
obtained from the proposed method was tested to compress and reconstruct the
reflectance spectra of the 1950 Natural Color System color chips and more than
50,000 ISO SOCS color patches as well as six multispectral images acquired by
multispectral image acquisition systems using 1600 glossy Munsell color chips as
training samples. The performance was evaluated by the mean values of color
differences between the original and reconstructed spectra under the CIE 1931
standard colorimetric observer and the CIE standard illuminants D50, D55, D65,
D75, F2, F7, F11, and A as well as five multichip white LED light sources. The
mean and maximum values of the root mean square errors between the original and
reconstructed spectra were also calculated. The experimental results show that
the proposed three LabLab interim connection spaces significantly outperform
principal component analysis, LabPQR, XYZLMS, Fairman-Brill, and LabRGB in
colorimetric reconstruction accuracy at the cost of slight reduction of spectral
reconstruction accuracy and illuminant independence of color differences of the
suggested LabLab interim connection spaces outperform other interim connection
spaces. In addition, the presented LabLab interim connection spaces could be
quite compatible with the extensively used colorimetric management system since
each dimension has definite colorimetric meanings and is perceptually uniform.
PMID- 27607512
TI - Monocular catadioptric panoramic depth estimation via caustics-based virtual
scene transition.
AB - Existing catadioptric panoramic depth estimation systems usually require two
panoramic imaging subsystems to achieve binocular disparity. The system
structures are complicated and only sparse depth maps can be obtained. We present
a novel monocular catadioptric panoramic depth estimation method that achieves
dense depth maps of panoramic scenes using a single unmodified conventional
catadioptric panoramic imaging system. Caustics model the reflection of the
curved mirror and establish the distance relationship between the virtual and
real panoramic scenes to overcome the nonlinear problem of the curved mirror.
Virtual scene depth is then obtained by applying our structure classification
regularization to depth from defocus. Finally, real panoramic scene depth is
recovered using the distance relationship. Our method's effectiveness is
demonstrated in experiments.
PMID- 27607513
TI - Performance comparison of fully adaptive and static passive polarimetric imagers
in the presence of intensity and polarization contrast.
AB - We address the comparison of contrast improvement obtained with a fully adaptive
polarimetric imager and the best channel of a static polarimetric imager in the
presence of both intensity and polarization differences between the target and
the background. We develop an in-depth quantitative study of the performance loss
incurred by a static imager compared to a fully adaptive one in this case. These
results are useful to make a well-informed choice between these two polarimetric
imaging architectures in a given application.
PMID- 27607514
TI - Recognizing blurred, nonfrontal, illumination, and expression variant partially
occluded faces.
AB - The focus of this paper is on the problem of recognizing faces across space
varying motion blur, changes in pose, illumination, and expression, as well as
partial occlusion, when only a single image per subject is available in the
gallery. We show how the blur, incurred due to relative motion between the camera
and the subject during exposure, can be estimated from the alpha matte of pixels
that straddle the boundary between the face and the background. We also devise a
strategy to automatically generate the trimap required for matte estimation.
Having computed the motion via the matte of the probe, we account for pose
variations by synthesizing from the intensity image of the frontal gallery a face
image that matches the pose of the probe. To handle illumination, expression
variations, and partial occlusion, we model the probe as a linear combination of
nine blurred illumination basis images in the synthesized nonfrontal pose, plus a
sparse occlusion. We also advocate a recognition metric that capitalizes on the
sparsity of the occluded pixels. The performance of our method is extensively
validated on synthetic as well as real face data.
PMID- 27607515
TI - Losing focus: how lens position and viewing angle affect the function of
multifocal lenses in fishes.
AB - Light rays of different wavelengths are focused at different distances when they
pass through a lens (longitudinal chromatic aberration [LCA]). For animals with
color vision this can pose a serious problem, because in order to perceive a
sharp image the rays must be focused at the shallow plane of the photoreceptor's
outer segments in the retina. A variety of fish and tetrapods have been found to
possess multifocal lenses, which correct for LCA by assigning concentric zones to
correctly focus specific wavelengths. Each zone receives light from a specific
beam entrance position (BEP) (the lateral distance between incoming light and the
center of the lens). Any occlusion of incoming light at specific BEPs changes the
composition of the wavelengths that are correctly focused on the retina. Here, we
calculated the effect of lens position relative to the plane of the iris and
light entering the eye at oblique angles on how much of the lens was involved in
focusing the image on the retina (measured as the availability of BEPs). We used
rotational photography of fish eyes and mathematical modeling to quantify the
degree of lens occlusion. We found that, at most lens positions and viewing
angles, there was a decrease of BEP availability and in some cases complete
absence of some BEPs. Given the implications of these effects on image quality,
we postulate that three morphological features (aphakic spaces, curvature of the
iris, and intraretinal variability in spectral sensitivity) may, in part, be
adaptations to mitigate the loss of spectral image quality in the periphery of
the eyes of fishes.
PMID- 27607516
TI - Evaluation of DNA barcode candidates for the discrimination of Artemisia L.
AB - Because of the very similar morphologies and wide diversity of Artemisia L.
varieties, they are difficult to identify, and there have been many arguments
about the systematic classification Artemisia L., especially concerning the
division of species. DNA barcode technology is used to rapidly identify species
based on standard short DNA sequences. To evaluate seven candidate DNA barcodes
(ITS, ITS2, psbA-trnH, rbcL, matK, rpoB, and rpoC1) regarding their ability to
identify closely related species of the Artemisia genus in Xinjiang. The
corresponding PCR amplification efficiency, detectable genetic divergence,
identification efficiency and phylogenetic tree were assessed. We found that the
internal transcribed spacer (ITS) region exhibited the highest interspecific
divergence, which was significantly higher than the observed intraspecific
variation and showed the highest identification efficiency, followed by ITS2,
psbA-trnH and, finally, rpoB. matK, rbcL, and rpoC1 performed poorly in this
evaluation. ITS, ITS2, and psbA-trnH were able to perfectly identify the tested
species Artemisia annua, A. absinthium, A. rupestris, A. tonurnefortiana, A.
austriaca, A. dracunculus, A. vulgaris, and A. macrocephala. Therefore, we
propose the ITS, ITS2, and psbA-trnH regions as promising DNA barcodes for the
closely related species of Artemisia L. in Xinjiang.
PMID- 27607517
TI - Does noninvasive electrical stimulation of acupuncture points reduce heelstick
pain in neonates?
AB - AIM: Noninvasive electrical stimulation at acupuncture points (NESAP) for
analgesia is used in children, but has not been widely studied in neonates. The
purpose of this study was to determine whether NESAP alone or in combination with
sucrose relieved heelstick pain in neonates. METHODS: Term neonates (n = 162)
receiving routine heelsticks for newborn screening were enrolled following
parental consent. All infants received facilitated tucking and non-nutritive
sucking. Neonates were randomised to standard care, sucrose, NESAP or sucrose
plus NESAP. NESAP (3.5 mA, 10 Hz) or sham was administered over four acupuncture
points. The Premature Infant Pain Profile (PIPP), heart rate variability (HRV)
and salivary cortisol were used to measure heelstick pain. RESULTS: PIPP scores
among all four treatment groups increased during heelstick, F (9,119) = 1.95, p =
0.05 and NESAP therapy had no significant effect on PIPP scores. However, PIPP
scores from baseline to heelstick increased the most in the two groups not
receiving sucrose (p < 0.01). Mean PIPP scores remained below five during the
heelstick in all four groups, indicating minimal or no pain. Differences in HRV
and salivary cortisol among groups were insignificant. CONCLUSION: NESAP at 3.5
mA, 10 Hz is not effective in relieving pain during heelsticks in neonates.
PMID- 27607518
TI - Polymerization under Hypersaline Conditions: A Robust Route to Phenolic Polymer
Derived Carbon Aerogels.
AB - Polymer-derived carbon aerogels can be obtained by direct polymerization of
monomers under hypersaline conditions using inorganic salts. This allows for
significantly increased mechanical robustness and avoiding special drying
processes. This concept was realized by conducting the polymerization of phenol
formaldehyde (PF) in the presence of ZnCl2 salt. Afterwards, the simultaneous
carbonization and foaming process conveniently converts the PF monolith into a
foam-like carbon aerogel. ZnCl2 plays a key role, serving as dehydration agent,
foaming agent, and porogen. The carbon aerogels thus obtained are of very low
density (25 mg cm-3 ), high specific surface area (1340 m2 g-1 ), and have a
large micro- and mesopore volume (0.75 cm3 g-1 ). The carbon aerogels show very
promising potential in the separation/extraction of organic pollutants and for
energy storage.
PMID- 27607519
TI - Gingival crevicular fluid volume and periodontal parameters alterations after use
of conventional and self-ligating brackets.
AB - OBJECTIVE: The aim of this study was to evaluate the alterations on plaque index
(PI), gingival index (GI), gingival bleeding index (GBI), and gingival crevicular
fluid (GCF) volume after use of three different brackets types for 60 days.
Setting Participants: The sample comprised 20 patients of both sexes aged 11-15
years (mean age: 13.3 years), with permanent dentition, adequate oral hygiene,
and mild tooth crowding, overjet, and overbite. METHODS: A conventional metallic
bracket GeminiTM, and two different brands of self-ligating brackets - In
Ovation(r)R and SmartClipTM - were bonded to the maxillary incisors and canines.
PI, GI, GBI scores, and GCF volume were measured before and 30 and 60 days after
bonding of the brackets. Data were analysed statistically using non-parametric
tests coefficient at a 5% significance level. RESULTS: There was no statistically
significant correlation (P > 0.05) between tooth crowding, overjet, and overbite
and the PI, GI, GBI scores, and GCF volume before bonding, indicating no
influence of malocclusion on the clinical parameters. Regardless of the bracket
design, no statistically significant difference (P > 0.05) was found for GI, GBI
scores. PI and GCF volume showed a significant difference among the brackets in
different periods. In pairwise comparisons a significant difference was observed
when compared before with 60 days after bonding, for the teeth bonded with
SmartClipTM self-ligating bracket, (PI P = 0.009; GCF volume P = 0.001).
CONCLUSION: There was an increase in PI score and GCF volume 60 days after
bonding of SmartClipTM self-ligating brackets, indicating the influence of
bracket design on these clinical parameters.
PMID- 27607520
TI - A 3-dimensional micro- and nanoparticle transport and filtration model (MNM3D)
applied to the migration of carbon-based nanomaterials in porous media.
AB - Engineered nanoparticles (NPs) in the environment can act both as contaminants,
when they are unintentionally released, and as remediation agents when injected
on purpose at contaminated sites. In this work two carbon-based NPs are
considered, namely CARBO-IRON(r), a new material developed for contaminated site
remediation, and single layer graphene oxide (SLGO), a potential contaminant of
the next future. Understanding and modeling the transport and deposition of such
NPs in aquifer systems is a key aspect in both cases, and numerical models
capable to simulate NP transport in groundwater in complex 3D scenarios are
necessary. To this aim, this work proposes a modeling approach based on modified
advection-dispersion-deposition equations accounting for the coupled influence of
flow velocity and ionic strength on particle transport. A new modeling tool
(MNM3D - Micro and Nanoparticle transport Model in 3D geometries) is presented
for the simulation of NPs injection and transport in 3D scenarios. MNM3D is the
result of the integration of the numerical code MNMs (Micro and Nanoparticle
transport, filtration and clogging Model - Suite) in the well-known transport
model RT3D (Clement et al., 1998). The injection in field-like conditions of
CARBO-IRON(r) (20g/l) amended by CMC (4g/l) in a 2D vertical tank (0.7*1.0*0.12m)
was simulated using MNM3D, and compared to experimental results under the same
conditions. Column transport tests of SLGO at a concentration (10mg/l)
representative of a possible spill of SLGO-containing waste water were performed
at different values of ionic strength (0.1 to 35mM), evidencing a strong
dependence of SLGO transport on IS, and a reversible blocking deposition. The
experimental data were fitted using the numerical code MNMs and the ionic
strength-dependent transport was up-scaled for a full scale 3D simulation of SLGO
release and long-term transport in a heterogeneous aquifer. MNM3D showed to
potentially represent a valid tool for the prediction of the long-term behavior
of engineered nanoparticles released in the environment (e.g. from landfills),
and the preliminary design of in situ aquifer remediation through injection of
suspensions of reactive NPs.
PMID- 27607526
TI - Understanding the patient experience through the power of film: A mixed method
qualitative research study.
AB - BACKGROUND: For decades film has proved to be a powerful form of communication.
Whether produced as entertainment, art or documentary, films have the capacity to
inform and move us. Films are a highly attractive teaching instrument and an
appropriate teaching method in health education. It is a valuable tool for
studying situations most transcendental to human beings such as pain, disease and
death. OBJECTIVES: The objectives were to determine how this helps students
engage with their role as health care professionals; to determine how they view
the personal experience of illness, disease, disability or death; and to
determine how this may impact upon their provision of patient care. DESIGN,
SETTING AND PARTICIPANTS: The project was underpinned by the film selection
determined by considerate review, intensive scrutiny, contemplation and discourse
by the research team. 7 films were selected, ranging from animation; foreign,
documentary, biopic and Hollywood drama. Each film was shown discretely, in an
acoustic lecture theatre projected onto a large screen to pre-registration
student nurses (adult, child and mental health) across each year of study from
different cohorts (n=49). METHOD: A mixed qualitative method approach consisted
of audio-recorded 5-minute reactions post film screening; coded questionnaires;
and focus group. Findings were drawn from the impact of the films through
thematic analysis of data sets and subjective text condensation categorised as:
new insights looking through patient eyes; evoking emotion in student nurses;
spiritual care; going to the moves to learn about the patient experience; self
discovery through films; using films to link theory to practice. RESULTS: Deeper
learning through film as a powerful medium was identified in meeting the
objectives of the study. Integration of film into pre registration curriculum,
pedagogy, teaching and learning is recommended. CONCLUSION: The teaching
potential of film stems from the visual process linked to human emotion and
experience. Its impact has the power to not only help in learning the values that
underpin nursing, but also for respecting the patient experience of disease,
disability, death and its reality.
PMID- 27607529
TI - Intragraft and Systemic Immune Parameters Discriminating Between Rejection and
Long-Term Graft Function in a Preclinical Model of Intestinal Transplantation.
AB - BACKGROUND: The pathology and diagnosis of acute and chronic rejection in
intestinal transplantation (ITX) are far from being completely understood. We
established models of acute and chronic intestinal graft rejection and analyzed
peripheral and intragraft immune responses. METHODS: We performed ITX from Dark
Agouti into Lewis rats applying single-dose tacrolimus (TAC) at varying
concentrations. Graft histology and immunohistology were assessed on
postoperative day (POD)7, 14, and 45. Intragraft and peripheral gene expressions
of inflammatory and anti-inflammatory markers and lipopolysaccharide binding
protein (LBP) plasma as well as alloantibodies were measured simultaneously.
RESULTS: A 1-mg TAC resulted in acute rejection and recipient death; 3 mg and 5
mg prolonged survival and led to severe or moderate chronic rejection,
respectively, with 50% of the 5-mg TAC recipients surviving the observation
period. Consequently, we observed severe infiltration on POD7 in untreated and 1
mg TAC recipients compared with minor histological alterations in 3 and 5 mg TAC
groups. Only 5-mg TAC treatment prevented accumulation of CD4+ T cells and ED1+
macrophages over the entire observation period. Peripheral and intragraft
expressions of T cell activation inhibitor-mitochondrial were stable in long-term
surviving 5-mg TAC recipients but declined before acute or chronic rejection in 1
and 3 mg TAC recipients. In contrast, LBP levels increased during acute and
chronic rejections. CONCLUSIONS: We studied acute and chronic rejections in a
preclinical model of ITX, which recapitulates clinical findings and highlights
the importance of monitoring peripheral T cell activation inhibitor-mitochondrial
expression, LBP levels, and antidonor antibodies for revealing rejection.
PMID- 27607532
TI - Revisiting APOLT for Metabolic Liver Disease: A New Look at an Old Idea.
AB - Even though auxiliary partial orthotopic liver transplantation (APOLT) as a
technique was popularized in the late 80s, its role in metabolic liver disease
remains controversial. The slow progress in gene therapy research, high incidence
of technical complications, and the problem of long term graft atrophy have been
roadblocks to its wider application. Better understanding of reciprocal dynamics
of portal flow and regeneration between the graft and native liver along with
multiple refinements in surgical technique have improved the outcomes of this
operation, making it a safe alternative to orthotopic liver transplantation for
patients with a wide range of noncirrhotic metabolic liver diseases (NCMLD). The
ability to perform APOLT safely has also opened up a range of exciting
indications in the setting of NCMLD. This article reviews the current status of
APOLT for NCMLD, technical refinements which have improved outcomes and novel
indications, which have rekindled fresh interest in this procedure.
PMID- 27607530
TI - Notch Signaling and Alloreactivity.
AB - Solid organ and allogeneic hematopoietic cell transplantation have become
standard therapeutic interventions that save patient lives and improve quality of
life. Our enhanced understanding of transplantation immunobiology has refined
clinical management and improved outcomes. However, organ rejection and graft
versus-host disease remain major obstacles to the broader successful application
of these therapeutic procedures. Notch signaling regulates multiple aspects of
adaptive and innate immunity. Preclinical studies identified Notch signaling as a
promising target in autoimmune diseases, as well as after allogeneic
hematopoietic cell and solid organ transplantation. Notch was found to be a
central regulator of alloreactivity across clinically relevant models of
transplantation. Notch inhibition in T cells prevented graft-versus-host disease
and organ rejection, establishing organ tolerance by skewing CD4 T helper
polarization away from a proinflammatory response toward suppressive regulatory T
cells. Notch ligand blockade also dampened alloantibody deposition and prevented
chronic rejection through humoral mechanisms. Toxicities of systemic Notch
blockade were observed with gamma-secretase inhibitors in preclinical and early
clinical trials across different indications, but they did not arise upon
preclinical targeting of Delta-like Notch ligands, a strategy sufficient to
confer full benefits of Notch ablation in T cell alloimmunity. Because multiple
clinical grade reagents have been developed to target individual Notch ligands
and receptors, the benefits of Notch blockade in transplantation are calling for
translation of preclinical findings into human transplantation medicine.
PMID- 27607533
TI - Short-term Pharmacological Inhibition of MyD88 Homodimerization by a Novel
Inhibitor Promotes Robust Allograft Tolerance in Mouse Cardiac and Skin
Transplantation.
AB - BACKGROUND: Most strategies for antirejection and tolerance induction in clinical
transplantation have focused on modifying adaptive immunity, it is unclear
whether pharmacological suppressing the innate immune system can promote
transplant tolerance. METHODS: We inhibited innate immunity by using our self
generated inhibitor of myeloid differentiation factor 88 (MyD88), TJ-M2010-5, and
investigated its therapeutic effects and mechanisms in cardiac and skin
transplant models. RESULTS: TJ-M2010-5 directly and indirectly interacted with
the Toll/IL-1R domain of MyD88, inhibiting MyD88 homodimerization. In vitro, TJ
M2010-5 inhibited maturation of dendritic cells, which suppressed nuclear
translocation of NF-kappaB and T cell activation. In vivo, short-term (10 days)
monotherapy of TJ-M2010-5 resulted in long time survival of 50% of the cardiac
allografts, and longer-term (14 days) combination treatment of TJ-M2010-5 with
CD154 mAb resulted in survival of 29% of skin allografts, which outperformed far
more than CsA did and stimulated the proliferation of CD4CD25FoxP3 Regulatory T
cells in recipient mice. CONCLUSIONS: Pharmacological inhibition of MyD88
signaling by this novel inhibitor TJ-M2010-5 shows a powerful anti-rejection
effect, which may have therapeutic potential in clinical transplantation. The
inhibition of both innate and adaptive immunity may be necessary for tolerance
induction in nonsolid organs.
PMID- 27607534
TI - Systemic Transplantation of Bone Marrow Mononuclear Cells Promotes Axonal
Regeneration and Analgesia in a Model of Wallerian Degeneration.
AB - BACKGROUND: Reinnervation timing after nerve injury is critical for favorable
axonal regeneration, remyelination, and clinical improvement. Considering bone
marrow mononuclear cells (BMMC) are easily obtained and readily available for
transplant, this work analyzed the effect of BMMC systemic administration on
nerve repair and pain behavior. METHODS: Adult rats with sciatic nerve crush were
immediately and systemically injected BMMC through the caudal artery. Nontreated,
sham and naive rats were also included. Histological, immunohistochemical,
biochemical, functional, and behavioral analyses were performed in nerves
harvested from each group at different survival times. RESULTS: Axons in BMMC
treated rats exhibited a more conserved morphological appearance than those in
nontreated rats, as observed at different survival times both in semithin
sections and ultrastructural analysis. BMMC-treated rats also showed a reduction
in major myelin protein immunoreactive clusters 7 and 14 days postinjury, as
compared with nontreated rats. Electrophysiological analysis showed BMMC
treatment to slightly improve the amplitude of compound muscle action potential
starting at 14 days postinjury. Finally, mechanical withdrawal threshold revealed
a full preventive action against transient mechanical hypersensitivity in BMMC
treated rats. CONCLUSIONS: These data demonstrate the efficiency of BMMC,
systemically and noninvasively transplanted, in correcting morphological,
functional and behavioral alterations resulting from peripheral nerve injury.
PMID- 27607535
TI - Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A
Systematic Review.
AB - BACKGROUND: The aim of this systematic review was to evaluate and compare the
pros and cons of using living donors or brain-dead donors in uterus
transplantation programs, 2 years after the first worldwide live birth after
uterus transplantation. METHODS: The Medline database and the Central Cochrane
Library were used to locate uterine transplantation studies carried out in human
or nonhuman primates. All types of articles (case reports, original studies, meta
analyses, reviews) in English or French were considered for inclusion. RESULTS:
Overall, 92 articles were screened and 44 were retained for review. Proof of
concept for human uterine transplantation was demonstrated in 2014 with a living
donor. Compared with a brain-dead donor strategy, a living donor strategy offers
greater possibilities for planning surgery and also decreases cold ischemia time,
potentially translating into a higher success rate. However, this approach poses
ethical problems, given that the donor is exposed to surgery risks but does not
derive any direct benefit. A brain-dead donor strategy is more acceptable from an
ethical viewpoint, but its feasibility is currently unproven, potentially owing
to a lack of compatible donors, and is associated with a longer cold ischemia
time and a potentially higher rejection rate. CONCLUSIONS: The systematic review
demonstrates that uterine transplantation is a major surgical innovation for the
treatment of absolute uterine factor infertility. Living and brain-dead donor
strategies are not mutually exclusive and, in view of the current scarcity of
uterine grafts and the anticipated future rise in demand, both will probably be
necessary.
PMID- 27607536
TI - Prevalence of the Uveitides in the United States.
PMID- 27607537
TI - Risk of colorectal neoplasia in patients with colonic diverticula.
PMID- 27607539
TI - Dispersing artifacts in FT-STS: a comparison of set point effects across
acquisition modes.
AB - Fourier-transform scanning tunnelling spectroscopy (FT-STS), or quasiparticle
interference, has become an influential tool for the study of a wide range of
important materials in condensed matter physics. However, FT-STS in complex
materials is often challenging to interpret, requiring significant theoretical
input in many cases, making it crucial to understand potential artifacts of the
measurement. Here, we compare the most common modes of acquiring FT-STS data and
show through both experiment and simulations that artifact features can arise
that depend on how the tip height is stabilized throughout the course of the
measurement. The most dramatic effect occurs when a series of dI/dV maps at
different energies are acquired with simultaneous constant current feedback; here
a feature that disperses in energy appears that is not observed in other
measurement modes. Such artifact features are similar to those arising from real
physical processes in the sample and are susceptible to misinterpretation.
PMID- 27607538
TI - Lithium Hexamethyldisilazane Transformation of Transiently Protected 4
Aza/Benzimidazole Nitriles to Amidines and their Dimethyl Sulfoxide Mediated
Imidazole Ring Formation.
AB - Trimethylsilyl-transient protection successfully allowed the use of lithium
hexamethyldisilazane to prepare benzimidazole (BI) and 4-azabenzimidazole (azaBI)
amidines from nitriles in 58-88% yields. This strategy offers a much better
choice to prepare BI/azaBI amidines than the lengthy, low-yielding Pinner
reaction. Synthesis of aza/benzimidazole rings from aromatic diamines and
aldehydes was affected in dimethyl sulfoxide in 10-15 min, while known procedures
require long time and purification. These methods are important for the BI/azaBI
based drug industry and for developing specific DNA binders for expanded
therapeutic applications.
PMID- 27607540
TI - Doping control analysis of anabolic steroids in equine urine by gas
chromatography-tandem mass spectrometry.
AB - Anabolic steroids are banned substances in equine sports. Gas chromatography-mass
spectrometry (GC-MS) has been the traditional technique for doping control
analysis of anabolic steroids in biological samples. Although liquid
chromatography-mass spectrometry (LC/MS) has become an important technique in
doping control, the detection of saturated hydroxysteroids by LC-MS remains a
problem due to their low ionization efficiency under electrospray. The recent
development in fast-scanning gas-chromatography-triple-quadrupole mass
spectrometry (GC-MS/MS) has provided a better alternative with a significant
reduction in chemical noise by means of selective reaction monitoring. Herein, we
present a sensitive and selective method for the screening of over 50 anabolic
steroids in equine urine using gas chromatography-tandem mass spectrometry (GC
MS/MS). Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27607542
TI - Collaborative arrangements and privately practising nurse practitioners in
Australia: results from a national survey.
AB - Objective Since the introduction of legislative changes in 2010, services
provided by privately practising nurse practitioners (PPNPs) in Australia have
been eligible for subsidisation through the Medicare Benefits Schedule (MBS) and
Pharmaceutical Benefits Scheme (PBS). To provide eligible services, PPNPs must
collaborate formally with a medical practitioner or an entity that employs
medical practitioners. This paper provides data from a national survey on these
collaborative arrangements in Australia. The aim of the study was to evaluate the
impact of PPNP services on patient access to care in Australia. Methods PPNPs in
Australia were invited to complete an electronic survey. Quantitative data were
analysed using descriptive statistics, whereas qualitative data were analysed
using thematic analysis. Seventy-three surveys were completed. Results Ninety
three per cent of participants reported having a collaborative arrangement in
place. Frequency of communication ranged from daily (27%) to never (1%).
Participants reported that collaborative arrangements facilitate learning,
patient care and offer support to PPNPs. However, for some PPNPs, organising a
formal collaborative arrangement is demanding because it is dependent on the
availability and willingness of medical practitioners and the open interpretation
of the arrangement. Only 19% of participants believed that collaborative
arrangements should be a prerequisite for PPNPs to access the MBS and PBS.
Conclusion Although there are benefits to collaborative arrangements, there is
also concern from PPNPs that mandating such arrangements through legislation
presents a barrier to establishing PPNP services and potentially reduces patient
access to care. Collaboration with medical practitioners is intrinsic to nursing
practice. Thus, legislating for collaborative arrangements is unnecessary,
because it makes the normal abnormal. What is known about the topic? To access
the MBS and PBS, PPNPs are required by law to have a collaborative arrangement
with a medical practitioner or entity that employs medical practitioners. To
date, the effects of these collaborative arrangements on PPNP services in
Australia have not been known. What does the paper add? This paper provides
unique data from a national survey on collaborative arrangements between PPNPs
and medical practitioners in Australia. What are the implications for
practitioners? Although there are benefits to collaborative arrangements, there
is also concern that mandating such arrangements presents a barrier to
establishing PPNP services and potentially reduces patient access to care.
PMID- 27607541
TI - Deaths Related to Nontuberculous Mycobacterial Infections in the United States,
1999-2014.
AB - RATIONALE: Unlike tuberculosis, nontuberculous mycobacterial disease is not
reportable to public health authorities in the United States, and the total
burden of disease is uncertain. OBJECTIVES: To estimate the mortality of
nontuberculous mycobacterial disease in the United States over a 15-year period
and to identify temporal trends. METHODS: The U.S. Multiple Cause of Death Files
from 1999 through 2014 were searched for a listing of nontuberculous
mycobacterial disease by International Classification of Diseases, Tenth Revision
code as either the underlying or a contributing cause of death. Characteristics
of individuals with nontuberculous mycobacteria-related deaths in the United
States were summarized according to demographic characteristics. Age-adjusted
mortality rates and rate ratios were calculated using bridged-race population
estimates of U.S. census population data. Time trends were evaluated with
negative binomial regression. MEASUREMENTS AND MAIN RESULTS: There was a
significant increase in nontuberculous mycobacteria-related deaths among
individuals without a diagnosis of HIV infection (P = 0.004). Mortality rates
increased with advancing age. Age-adjusted mortality rate ratios were lower for
men (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.80-0.87) compared
with women, and were lower for Hispanic individuals (RR, 0.53; 95% CI, 0.49-0.56)
and black, non-Hispanic persons (RR, 0.83; 95% CI, 0.77-0.88) compared with
white, non-Hispanic individuals. CONCLUSIONS: The mortality rate of
nontuberculous mycobacterial disease among HIV-uninfected individuals has
increased in the United States between 1999 and 2014. These deaths occurred
disproportionately in older white women. Considering the concurrent decline in
tuberculosis-related deaths, these findings demonstrate a shift in the
epidemiology of fatal mycobacterial infections in the United States.
PMID- 27607544
TI - Multiple imputation of missing data in multilevel designs: A comparison of
different strategies.
AB - Multiple imputation is a widely recommended means of addressing the problem of
missing data in psychological research. An often-neglected requirement of this
approach is that the imputation model used to generate the imputed values must be
at least as general as the analysis model. For multilevel designs in which lower
level units (e.g., students) are nested within higher level units (e.g.,
classrooms), this means that the multilevel structure must be taken into account
in the imputation model. In the present article, we compare different strategies
for multiply imputing incomplete multilevel data using mathematical derivations
and computer simulations. We show that ignoring the multilevel structure in the
imputation may lead to substantial negative bias in estimates of intraclass
correlations as well as biased estimates of regression coefficients in multilevel
models. We also demonstrate that an ad hoc strategy that includes dummy
indicators in the imputation model to represent the multilevel structure may be
problematic under certain conditions (e.g., small groups, low intraclass
correlations). Imputation based on a multivariate linear mixed effects model was
the only strategy to produce valid inferences under most of the conditions
investigated in the simulation study. Data from an educational psychology
research project are also used to illustrate the impact of the various multiple
imputation strategies. (PsycINFO Database Record
PMID- 27607543
TI - A comparison of latent class, K-means, and K-median methods for clustering
dichotomous data.
AB - The problem of partitioning a collection of objects based on their measurements
on a set of dichotomous variables is a well-established problem in psychological
research, with applications including clinical diagnosis, educational testing,
cognitive categorization, and choice analysis. Latent class analysis and K-means
clustering are popular methods for partitioning objects based on dichotomous
measures in the psychological literature. The K-median clustering method has
recently been touted as a potentially useful tool for psychological data and
might be preferable to its close neighbor, K-means, when the variable measures
are dichotomous. We conducted simulation-based comparisons of the latent class, K
means, and K-median approaches for partitioning dichotomous data. Although all 3
methods proved capable of recovering cluster structure, K-median clustering
yielded the best average performance, followed closely by latent class analysis.
We also report results for the 3 methods within the context of an application to
transitive reasoning data, in which it was found that the 3 approaches can
exhibit profound differences when applied to real data. (PsycINFO Database Record
PMID- 27607545
TI - Estimating the standardized mean difference with minimum risk: Maximizing
accuracy and minimizing cost with sequential estimation.
AB - The standardized mean difference is a widely used effect size measure. In this
article, we develop a general theory for estimating the population standardized
mean difference by minimizing both the mean square error of the estimator and the
total sampling cost. Fixed sample size methods, when sample size is planned
before the start of a study, cannot simultaneously minimize both the mean square
error of the estimator and the total sampling cost. To overcome this limitation
of the current state of affairs, this article develops a purely sequential
sampling procedure, which provides an estimate of the sample size required to
achieve a sufficiently accurate estimate with minimum expected sampling cost.
Performance of the purely sequential procedure is examined via a simulation study
to show that our analytic developments are highly accurate. Additionally, we
provide freely available functions in R to implement the algorithm of the purely
sequential procedure. (PsycINFO Database Record
PMID- 27607547
TI - Clinical outcomes with a systolic blood pressure lower than 120 mmHg in older
patients with high disease burden.
AB - BACKGROUND: The target blood pressure in older patients is controversial. Recent
studies provided clinical evidence supporting a target systolic blood pressure
<120 mmHg in patients >50 years at high risk of cardiovascular events. METHODS:
Retrospective study of 380 consecutive patients >=60 years with stages 1-5 pre
dialysis chronic kidney disease seen between January 2013 and November 2015. The
outcomes of a systolic blood pressure <120 mmHg in older patients with chronic
kidney disease and multiple comorbidities were analyzed. RESULTS: Sixty-eight
patients had a systolic blood pressure <120 mmHg, 312 patients had a systolic
blood pressure >=120 mmHg. Forty-three patients died during the follow up
(11.3%). Patients with a systolic blood pressure <120 mmHg had a higher risk of
death: 21 (30.9%) vs 22 (7%). Primary cause of death: Cardiovascular: 11 (25.6%),
infectious 9 (20.9%), cancer 5 (11.6%), renal failure 6 (13.9%), COPD/pulmonary
fibrosis 2 (4.6%), end stage liver disease 3 (6.9%), traumatic brain injury 1
(2.3%), gastrointestinal hemorrhage 4 (9.3%), complications of diabetes 1 (2.3%),
unknown 1 (2.3%). After adjusting for confounding factors, a systolic blood
pressure <120 mmHg remained associated with increased mortality. There was a
trend to more cardiovascular outcomes in those with a lower blood pressure.
CONCLUSIONS: A systolic blood pressure below 120 mmHg in older patients with high
disease burden was associated with adverse outcomes. Individualization of blood
pressure therapy to each specific patient is warranted.
PMID- 27607546
TI - An Effective Design of Electrically Conducting Thin-Film Composite (TFC)
Membranes for Bio and Organic Fouling Control in Forward Osmosis (FO).
AB - The organic foulants and bacteria in secondary wastewater treatment can seriously
impair the membrane performance in a water treatment plant. The embedded
electrode approach using an externally applied potential to repel organic
foulants and inhibit bacterial adhesion can effectively reduce the frequency of
membrane replacement. Electrode embedment in membranes is often carried out by
dispensing a conductor (e.g., carbon nanotubes, or CNTs) in the membrane
substrate, which gives rise to two problems: the leaching-out of the conductor
and a percolation-limited membrane conductivity that results in an added energy
cost. This study presents a facile method for the embedment of a continuous
electrode in thin-film composite (TFC) forward osmosis (FO) membranes.
Specifically, a conducting porous carbon paper is used as the understructure for
the formation of a membrane substrate by the classical phase inversion process.
The carbon paper and the membrane substrate polymer form an interpenetrating
structure with good stability and low electrical resistance (only about
1Omega/?). The membrane-electrode assembly was deployed as the cathode of an
electrochemical cell, and showed good resistance to organic and microbial fouling
with the imposition of a 2.0 V DC voltage. The carbon paper-based FO TFC
membranes also possess good mechanical stability for practical use.
PMID- 27607548
TI - Visualization of subsurface nanoparticles in a polymer matrix using resonance
tracking atomic force acoustic microscopy and contact resonance spectroscopy.
AB - A visualization technique of subsurface features with a nanometer-scale spatial
resolution is strongly demanded. Some research groups have demonstrated the
visualization of subsurface features using various techniques based on atomic
force microscopy. However, the imaging mechanisms have not yet been fully
understood. In this study, we demonstrated the visualization of subsurface Au
nanoparticles buried in a polymer matrix 900 nm from the surface using two
techniques; i.e., resonance tracking atomic force acoustic microscopy and contact
resonance spectroscopy. It was clarified that the subsurface features were
visualized by the two techniques as the area with a higher contact resonance
frequency and a higher Q-factor than those in the surrounding area, which
suggests that the visualization is realized by the variation of the contact
stiffness and damping of the polymer matrix due to the existence of the buried
nanoparticles.
PMID- 27607549
TI - Feedback Control of Two-Component Regulatory Systems.
AB - Two-component systems are a dominant form of bacterial signal transduction. The
prototypical two-component system consists of a sensor that responds to a
specific input(s) by modifying the output of a cognate regulator. Because the
output of a two-component system is the amount of phosphorylated regulator,
feedback mechanisms may alter the amount of regulator, and/or modify the ability
of a sensor or other proteins to alter the phosphorylation state of the
regulator. Two-component systems may display intrinsic feedback whereby the
amount of phosphorylated regulator changes under constant inducing conditions and
without the participation of additional proteins. Feedback control allows a two
component system to achieve particular steady-state levels, to reach a given
steady state with distinct dynamics, to express coregulated genes in a given
order, and to activate a regulator to different extents, depending on the signal
acting on the sensor.
PMID- 27607550
TI - Metagenomics and the Human Virome in Asymptomatic Individuals.
AB - High-throughput sequencing technologies have revolutionized how we think about
viruses. Investigators can now go beyond pathogenic viruses and have access to
the thousands of viruses that inhabit our bodies without causing clinical
symptoms. By studying their interactions with each other, with other microbes,
and with host genetics and immune systems, we can learn how they affect health
and disease. This article reviews current knowledge of the composition and
diversity of the human virome in physiologically healthy individuals. It focuses
on recent results from metagenomics studies and discusses the contribution of
bacteriophages and eukaryotic viruses to human health.
PMID- 27607551
TI - Molecular Genetic Analysis of Chlamydia Species.
AB - Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the
leading cause of bacterial sexually transmitted diseases, significant respiratory
pathogens, and a zoonotic threat. Their dependence on an intracellular growth
niche and their peculiar developmental cycle are major challenges to elucidating
their biology and virulence traits. The last decade has seen tremendous advances
in our ability to perform a molecular genetic analysis of Chlamydia species.
Major achievements include the generation of large collections of mutant strains,
now available for forward- and reverse-genetic applications, and the introduction
of a system for plasmid-based transformation enabling complementation of
mutations; expression of foreign, modified, or reporter genes; and even targeted
gene disruptions. This review summarizes the current status of the molecular
genetic toolbox for Chlamydia species and highlights new insights into their
biology and new challenges in the nascent field of Chlamydia genetics.
PMID- 27607552
TI - The Atacama Desert: Technical Resources and the Growing Importance of Novel
Microbial Diversity.
AB - The Atacama Desert of northern Chile is the oldest and most arid nonpolar
environment on Earth. It is a coastal desert covering approximately 180,000
km(2), and together with the greater Atacama region it comprises a dramatically
wide range of ecological niches. Long known and exploited for its mineral
resources, the Atacama Desert harbors a rich microbial diversity that has only
recently been discovered; the great majority of it has not yet been recovered in
culture or even taxonomically identified. This review traces the progress of
microbiology research in the Atacama and dispels the popular view that this
region is virtually devoid of life. We examine reasons for such research activity
and demonstrate that microbial life is the latest recognized and least explored
resource in this inspiring biome.
PMID- 27607554
TI - Riboswitch-Mediated Gene Regulation: Novel RNA Architectures Dictate Gene
Expression Responses.
AB - Riboswitches are RNA elements that act on the mRNA with which they are
cotranscribed to modulate expression of that mRNA. These elements are widely
found in bacteria, where they have a broad impact on gene expression. The
defining feature of riboswitches is that they directly recognize a physiological
signal, and the resulting shift in RNA structure affects gene regulation. The
majority of riboswitches respond to cellular metabolites, often in a feedback
loop to repress synthesis of the enzymes used to produce the metabolite. Related
elements respond to the aminoacylation status of a specific tRNA or to a physical
parameter, such as temperature or pH. Recent studies have identified new classes
of riboswitches and have revealed new insights into the molecular mechanisms of
signal recognition and gene regulation. Application of structural and biophysical
approaches has complemented previous genetic and biochemical studies, yielding
new information about how different riboswitches operate.
PMID- 27607556
TI - Autophagy Evasion and Endoplasmic Reticulum Subversion: The Yin and Yang of
Legionella Intracellular Infection.
AB - The gram-negative bacterial pathogen Legionella pneumophila creates a novel
organelle inside of eukaryotic host cells that supports intracellular
replication. The L. pneumophila-containing vacuole evades fusion with lysosomes
and interacts intimately with the host endoplasmic reticulum (ER). Although the
natural hosts for L. pneumophila are free-living protozoa that reside in
freshwater environments, the mechanisms that enable this pathogen to replicate
intracellularly also function when mammalian macrophages phagocytose aerosolized
bacteria, and infection of humans by L. pneumophila can result in a severe
pneumonia called Legionnaires' disease. A bacterial type IVB secretion system
called Dot/Icm is essential for intracellular replication of L. pneumophila. The
Dot/Icm apparatus delivers over 300 different bacterial proteins into host cells
during infection. These bacterial proteins have biochemical activities that
target evolutionarily conserved host factors that control membrane transport
processes, which results in the formation of the ER-derived vacuole that supports
L. pneumophila replication. This review highlights research discoveries that have
defined interactions between vacuoles containing L. pneumophila and the host ER.
These studies reveal how L. pneumophila creates a vacuole that supports
intracellular replication by subverting host proteins that control biogenesis and
fusion of early secretory vesicles that exit the ER and host proteins that
regulate the shape and dynamics of the ER. In addition to recruiting ER-derived
membranes for biogenesis of the vacuole in which L. pneumophila replicates, these
studies have revealed that this pathogen has a remarkable ability to interfere
with the host's cellular process of autophagy, which is an ancient cell
autonomous defense pathway that utilizes ER-derived membranes to target
intracellular pathogens for destruction. Thus, this intracellular pathogen has
evolved multiple mechanisms to control membrane transport processes that center
on the involvement of the host ER.
PMID- 27607553
TI - Evolution and Ecology of Actinobacteria and Their Bioenergy Applications.
AB - The ancient phylum Actinobacteria is composed of phylogenetically and
physiologically diverse bacteria that help Earth's ecosystems function. As free
living organisms and symbionts of herbivorous animals, Actinobacteria contribute
to the global carbon cycle through the breakdown of plant biomass. In addition,
they mediate community dynamics as producers of small molecules with diverse
biological activities. Together, the evolution of high cellulolytic ability and
diverse chemistry, shaped by their ecological roles in nature, make
Actinobacteria a promising group for the bioenergy industry. Specifically, their
enzymes can contribute to industrial-scale breakdown of cellulosic plant biomass
into simple sugars that can then be converted into biofuels. Furthermore,
harnessing their ability to biosynthesize a range of small molecules has
potential for the production of specialty biofuels.
PMID- 27607557
TI - Electrochemical Fabrication of Monolithic Electrodes with Core/Shell Sandwiched
Transition Metal Oxide/Oxyhydroxide for High-Performance Energy Storage.
AB - Transition metal oxides/oxyhydroxides (TMOs) are promising high-capacity
materials for electrochemical energy storage. However, the low rate and poor
cyclability hinder practical applications. In this work, we developed a general
electrochemical route to fabricate monolithic core/shell sandwiched structures,
which are able to significantly improve the electrochemical properties of TMO
electrodes by electrically wiring the insulating active materials and alleviating
the adverse effects caused by volume changes using engineered porous structures.
As an example, a lithium ion battery anode of porous MnO sandwiched between CNT
and carbon demonstrates a high capacity of 554 mAh g-1 even after 1000 cycles at
2 A g-1. An all-solid-state symmetric pseudocapacitor consisting of
CNT@MnOOH@polypyrrole exhibits a high specific capacitance of 148 F g-1 and
excellent capacitance retention (92% after 10000 cycles at 2 A g-1). Several
other examples and applications have further confirmed the effectiveness of
improving the electrochemical properties by core/shell sandwiched structures.
PMID- 27607555
TI - Gut Microbiota, Inflammation, and Colorectal Cancer.
AB - Colorectal cancer is the second-leading cause of cancer-related deaths in the
United States and fourth-leading cause of cancer-related deaths worldwide. While
cancer is largely considered to be a disease of genetic and environmental
factors, increasing evidence has demonstrated a role for the microbiota (the
microorganisms associated with the human body) in shaping inflammatory
environments and promoting tumor growth and spread. Herein, we discuss both human
data from meta'omics analyses and data from mechanistic studies in cell culture
and animal models that support specific bacterial agents as potentiators of
tumorigenesis-including Fusobacterium nucleatum, enterotoxigenic Bacteroides
fragilis, and colibactin-producing Escherichia coli. Further, we consider how
microbes can be used in diagnosing colorectal cancer and manipulating the tumor
environment to encourage better patient outcomes in response to immunotherapy
treatments.
PMID- 27607560
TI - Erratum.
PMID- 27607559
TI - High Serum Tumor Necrosis Factor Levels in the Early Post-Cardiac Arrest Period
Are Associated with Poor Short-Term Survival in a Swine Model of Ventricular
Fibrillation.
AB - Most resuscitated victims of out-of-hospital cardiac arrest who survive to
hospital expire due to the postresuscitation syndrome. This syndrome is
characterized by a sepsis-like proinflammatory state. The objective of this
investigation was to determine whether a relationship exists between the rise of
tumor necrosis factor (TNF), a proinflammatory cytokine, following return of
spontaneous circulation (ROSC), and early postarrest survival in a clinically
relevant animal model of spontaneous ventricular fibrillation (VF). Mixed-breed
Yorkshire swine (n = 20), weighing 39 +/- 5 kg, were anesthetized and catheters
placed in the right atrium and left ventricle/ascending aorta for continuous
pressure monitoring. VF was induced by occluding the left anterior descending
coronary artery with an angioplasty balloon. After 7 min of untreated VF,
advanced life support resuscitation attempts were made for up to 20 min. Animals
achieving ROSC were monitored for 3 h and fluid and pressor support was
administered as needed. TNF levels were measured before VF and at 0, 15, and 30
min after ROSC using quantitative sandwich enzyme-linked immunosorbent assay.
Twelve (60%) animals experienced early death, expiring during the 3 hour
postarrest period (9 pulseless electrical activity, 2 VF, and 1 asystole). The
TNF level at 15 min post-ROSC was significantly associated with death within the
first 3 h post-ROSC with a univariate odds ratio of 1.4 [95% confidence interval
(CI) 1.05-2.2, P = 0.01]. Using a cutoff TNF level of 525 pg/mL at 15 min post
ROSC had 100% negative predictive value (95% CI 0%-37%) and 67% positive
predictive value (95% CI 35%-90%) for early death with a hazard ratio of 6.6 (95%
CI 1.9-23.5). TNF increases shortly after ROSC and is predictive of early death.
Early identification of resuscitated victims at greatest risk for hemodynamic
collapse and recurrent arrest might facilitate the use of early hospital-based
interventions to decrease the likelihood of a poor outcome.
PMID- 27607558
TI - Acute Ethanol Increases IGF-I-Induced Phosphorylation of ERKs by Enhancing
Recruitment of p52-Shc to the Grb2/Shc Complex.
AB - Ethanol plays a detrimental role in the development of the brain. Multiple
studies have shown that ethanol inhibits insulin-like growth factor I receptor
(IGF-IR) function. Because the IGF-IR contributes to brain development by
supporting neural growth, survival, and differentiation, we sought to determine
the molecular mechanism(s) involved in ethanol's effects on this membrane
associated tyrosine kinase. Using multiple neuronal cell types, we performed
Western blot, immunoprecipitation, and GST-pulldowns following acute (1-24 h) or
chronic (3 weeks) treatment with ethanol. Surprisingly, exposure of multiple
neuronal cell types to acute (up to 24 h) ethanol (50 mM) enhanced IGF-I-induced
phosphorylation of extracellular regulated kinases (ERKs), without affecting IGF
IR tyrosine phosphorylation itself, or Akt phosphorylation. This acute increase
in ERKs phosphorylation was followed by the expected inhibition of the IGF-IR
signaling following 3-week ethanol exposure. We then expressed a GFP-tagged IGF
IR construct in PC12 cells and used them to perform fluorescence recovery after
photobleaching (FRAP) analysis. Using these fluorescently labeled cells, we
determined that 50 mM ethanol decreased the half-time of the IGF-IR-associated
FRAP, which implied that cell membrane-associated signaling events could be
affected. Indeed, co-immunoprecipitation and GST-pulldown studies demonstrated
that the acute ethanol exposure increased the recruitment of p52-Shc to the Grb2
Shc complex, which is known to engage the Ras-Raf-ERKs pathway following IGF-1
stimulation. These experiments indicate that even a short and low-dose exposure
to ethanol may dysregulate function of the receptor, which plays a critical role
in brain development. J. Cell. Physiol. 232: 1275-1286, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27607561
TI - Rapid Laser Printing of Paper-Based Multilayer Circuits.
AB - Laser printing has been widely used in daily life, and the fabricating process is
highly efficient and mask-free. Here we propose a laser printing process for the
rapid fabrication of paper-based multilayer circuits. It does not require wetting
of the paper, which is more competitive in manufacturing paper-based circuits
compared to conventional liquid printing process. In the laser printed circuits,
silver nanowires (Ag-NWs) are used as conducting material for their excellent
electrical and mechanical properties. By repeating the printing process,
multilayer three-dimensional (3D) structured circuits can be obtained, which is
quite significant for complex circuit applications. In particular, the
performance of the printed circuits can be exactly controlled by varying the
process parameters including Ag-NW content and laminating temperature, which
offers a great opportunity for rapid prototyping of customized products with
designed properties. A paper-based high-frequency radio frequency identification
(RFID) label with optimized performance is successfully demonstrated. By
adjusting the laminating temperature to 180 degrees C and the top-layer Ag-NW
areal density to 0.3 mg cm(-2), the printed RFID antenna can be conjugately
matched with the chip, and a big reading range of ~12.3 cm with about 2.0 cm over
that of the commercial etched Al antenna is achieved. This work provides a
promising approach for fast and quality-controlled fabrication of multilayer
circuits on common paper and may be enlightening for development of paper-based
devices.
PMID- 27607562
TI - Time interval between infective endocarditis first symptoms and diagnosis:
relationship to infective endocarditis characteristics, microorganisms and
prognosis.
AB - OBJECTIVE: To analyze the characteristics and outcome of infective endocarditis
(IE) according to the time interval between IE first symptoms and diagnosis.
METHODS: Among the IE cases of a French population-based epidemiological survey,
patients having early-diagnosed IE (diagnosis of IE within 1 month of first
symptoms) were compared with those having late-diagnosed IE (diagnosis of IE more
than 1 month after first symptoms). RESULTS: Among the 486 definite-IE, 124 (25%)
had late-diagnosed IE whereas others had early-diagnosed IE. Early-diagnosed IE
were independently associated with female gender (OR = 1.8; 95% CI [1.0-3.0]),
prosthetic valve (OR= 2.6; 95% CI [1.4-5.0]) and staphylococci as causative
pathogen (OR = 3.7; 95% CI [2.2-6.2]). Cardiac surgery theoretical indication
rates were not different between early and late-diagnosed IE (56.3% vs 58.9%),
whereas valve surgery performance was lower in early-diagnosed IE (41% vs 53%; p
= .03). In-hospital mortality rates were higher in early-diagnosed IE than in
late-diagnosed IE (25.1% vs 16.1%; p < .001). CONCLUSIONS: The time interval
between IE first symptoms and diagnosis is closely related to the IE clinical
presentation, patient characteristics and causative microorganism. Better
prognosis reported in late-diagnosed IE may be related to a higher rate of
valvular surgery. KEY MESSAGES Infective endocarditis, which time interval
between first symptoms and diagnosis was less than one month, were mainly due to
Staphylococcus aureus in France. Staphylococcus aureus infective endocarditis
were associated with septic shock, transient ischemic attack or stroke and higher
mortality rates than infective endocarditis due to other bacteria or infective
endocarditis, which time interval between first symptoms and diagnosis was more
than one month. Infective endocarditis, which time interval between first
symptoms and diagnosis was more than one month, were accounting for one quarter
of all infective endocarditis in our study and were associated with vertebral
osteomyelitis and a higher rate of cardiac surgery performed for hemodynamic
indication than other infective endocarditis.
PMID- 27607564
TI - New minimally invasive technique for cystoscopic laser treatment of fetal
ureterocele.
AB - Prenatal ultrasound detection of fetal ureterocele with bilateral
hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic
fluid reduction have been associated with a significant risk of end-stage chronic
renal disease after birth. Fetal cystoscopic laser incision of the ureterocele,
using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal
bladder with the aim of relieving the bladder outflow obstruction to preserve
renal function, has been reported previously in a case with a favorable outcome.
We report on two additional cases of fetal ureterocele treated by cystoscopic
laser decompression. In the first case, a standard 3.3-mm uterine entry was used.
In the second case, a new approach was adopted using an 'all-seeing needle' 1.6
mm endoscope. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27607563
TI - Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a
progressive form of contractures.
AB - Dominant mutations in PIEZO2, which codes for the principal mechanotransduction
channel for proprioception and touch sensation, have been found to cause
different forms of distal arthrogryposis. Some observations suggest that these
dominant mutations induce a gain-of-function effect on the channel. Here, we
report a consanguineous family with three siblings who showed short stature,
scoliosis, gross motor impairment, and a progressive form of contractures
involving the distal joints that is distinct from that found in patients with
dominant mutations in PIEZO2. These siblings also displayed deficits in
proprioception and touch sensation. Whole-exome sequencing performed in the three
affected siblings revealed the presence of a rare homozygous variant (c.2708C>G;
p.S903*) in PIEZO2. This variant is predicted to disrupt PIEZO2 function by
abolishing the pore domain. Sanger sequencing confirmed that all three siblings
are homozygous whereas their parents and an unaffected sibling are heterozygous
for this variant. Recessive mutations in PIEZO2 thus appear to cause a
progressive phenotype that overlaps with, while being mostly distinct from that
associated with dominant mutations in the same gene.
PMID- 27607565
TI - Investigating Prevalence and Pattern of Long-term Cardiovascular Disorders in
Sulphur Mustard-exposed Victims and Determining Proper Biomarkers for Early
Defining, Monitoring and Analysis of Patients' Feedback on Therapy.
AB - Among the most readily existing chemical warfare agents, sulphur mustard (SM),
also known as mustard gas, is the most commonly used agent owing to its ease of
synthesis and stockpiling. Unprotected exposure mostly results in debilitation
rather than lethal injuries, leaving an exposed victim incapacitated for days to
even months. Although acute toxicity of sulphur mustard has been fairly
established, the long-term post-exposure effects either chronic or short-term but
significant are still evolving. A total of 30,000 Iranian victims of the Iran
Iraq imposed war have now - after 30 years - formed the key population
demonstrating long-term effects from sulphur mustard exposure. Recent studies
have shown that the prevalence of several long-term cardiovascular disorders
(CVDs) has significantly increased among SM-exposed victims including coronary
artery disorders (CAD), coronary artery ectasia (CAE), congestive heart failure
(CHF) and myocardium abnormalities. The more important point is the lack of a
determinant biomarker for early screening, recognizing, treating, monitoring and
estimating exposed victims' response to applied therapy. Additionally,
unidentified risk factors significantly decrease the chance of a successful
therapy and result in undesired failure of a comprehensive therapeutic strategy.
In this MiniReview, we examined the literature in detail to evaluate relevant
reports considering long-term cardiovascular complications of SM, detecting
possible risk factors and determining possible preventing events.
PMID- 27607566
TI - Vaccine Development for Zika Virus-Timelines and Strategies.
AB - Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and
Central America in 2015 to 2016. Microcephaly has been causally associated with
Zika virus infection during pregnancy and the World Health Organization declared
Zika virus as a Public Health Emergency of International Concern. To address this
crisis, many groups have expressed their commitment to developing a Zika virus
vaccine. Different strategies for Zika virus vaccine development are being
considered including recombinant live attenuated vaccines, purified inactivated
vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika
virus vaccine development will be the target group chosen for vaccination and
which end point(s) is chosen for efficacy determination. The first clinical
trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway
to licensure for a Zika virus vaccine is expected to take several years. Efforts
are ongoing to accelerate Zika virus vaccine development and evaluation with the
ultimate goal of reducing time to licensure.
PMID- 27607568
TI - Adjunctive Electroconvulsive Therapy for Schizophrenia: A Meta-analysis of
Randomized Rater-Masked Controlled Trials: Retraction.
PMID- 27607567
TI - Electroconvulsive Therapy Alone for Schizophrenia: A Meta-analysis of Randomized,
Single-blind, Controlled Trials: Retraction.
PMID- 27607569
TI - The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4
Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed
by Distinct Stereochemical Features.
AB - Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20
years have not improved the prognosis for patients, necessitating the development
of new treatments. We have previously reported the therapeutic potential of the
quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces
cell death by catastrophic vacuolization. Compound 1 is a mixture of four
stereoisomers due to the two adjacent stereogenic centers in the molecule,
complicating further development in the preclinical setting. This work describes
the isolation and characterization of the individual isomers of 1 and shows that
these display stereospecific pharmacokinetic and pharmacodynamic features. In
addition, we present a stereoselective synthesis of the active isomers, providing
a basis for further development of this compound series into a novel experimental
therapeutic for glioblastoma.
PMID- 27607570
TI - A Structurally Variable Porous Organic Salt Based on a Multidirectional
Supramolecular Cluster.
AB - A porous organic salt (POS) composed of 2-sulfophenyl anthracene (2-SPA) and
triphenylmetylamine (TPMA) forms five types of porous crystals, POS-a-e, by
recognizing subtle differences in the molecular structure of incorporated guest
molecules. This structurally variable POS was hierarchically designed on the
basis of a supramolecular cluster with a directionally flexible linker formed by
the organic salt. X-ray crystallographic analysis reveals that the salt forms six
conformers attributable to rocking and rotational motions of the phenylene group
in 2-SPA. The clusters form POS crystals through different porous networks
according to the conformers. The POS crystals show a wide range of fluorescence
spectra that are responsive to differences in the molecular and electronic
structure of the guest molecule. This remarkable behavior has potential
application in sensitive chemical sensors that are responsive to slight
differences in molecular structures.
PMID- 27607572
TI - A national survey on the management of psoriatic arthritis using the Delphi
method.
AB - OBJECTIVES: Accurate diagnosis and appropriate management of psoriatic arthritis
(PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to
evaluate the current approach to the management of PsA among rheumatologists.
METHODS: A 16-item online questionnaire, produced using the Delphi method, was
submitted to a panel of rheumatologists who anonymously expressed their opinions
on a scale from 1 (maximum disagreement) to 5 (maximum agreement). Positive
consensus was defined by >=66% of the respondents scoring an item 3, 4 or 5.
Negative consensus was defined by >=66% of the respondents scoring an item 1 or
2. RESULTS: The surveyed rheumatologists agreed that in its early stage, PsA is
characterised by the involvement of few joints and/or entheses and that
psoriasis, although possibly absent, will be present in a patient's past personal
or family history. There was no consensus among the rheumatologists regarding
normalisation of C-reactive protein levels and erythrocyte sedimentation rates
defining remission. The specialists believed that clinical remission was achieved
more frequently and for longer among patients with PsA than rheumatoid arthritis.
The participants believed that neutralising antibodies altered the efficacy of
anti-tumour necrosis factor agents and that monoclonal antibodies induced greater
production of neutralising antibodies than receptor proteins. However, knowledge
was somewhat lacking in relation to the prophylaxis of latent tuberculosis.
CONCLUSIONS: The data collected showed that the surveyed rheumatologists had a
good knowledge of the diagnosis of early-stage PsA and a good understanding of
its management in relation to its clinical phenotype, with the exception of the
form having predominantly axial involvement.
PMID- 27607571
TI - Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS
trial.
AB - AIM: To examine fracture incidence among participants in the Trial Evaluating
Cardiovascular Outcomes with Sitagliptin (TECOS). RESEARCH DESIGN AND METHODS: We
used data from 14 671 participants in the TECOS study who were randomized double
blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture
incidence rates were calculated and their association with study treatment
assignment was examined using multivariable Cox proportional hazards regression.
RESULTS: The baseline mean (standard deviation) participant age was 65.5 (8.0)
years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was
7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1%
were non-white. During 43 222 person-years' follow-up, 375 (2.6%; 8.7 per 1000
person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34;
upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed
fracture risk increased independently with older age (P < .001), female sex (P <
.001), white race (P < .001), lower diastolic blood pressure (P < .001) and
diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not
associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted
hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944;
adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip
fractures (P = .761). Insulin therapy was associated with a higher fracture risk
(HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76,
95% CI 0.59-0.98; P = .035). CONCLUSION: Fractures were common among people with
diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin
and metformin treatment were associated with higher and lower fracture risks,
respectively.
PMID- 27607573
TI - Liability and Informed Consent in the Context of Shared Decision Making.
AB - The idea of shared decision making (SDM) is gaining traction within emergency
medicine, although concerns about potential legal consequences of its use may be
slowing its adoption. We describe the similarities and differences between
informed consent (IC) requirements and SDM, highlighting their different
purposes, scope, and implementation. We also illustrate several areas in which
SDM may affect clinicians' liability risks and suggest that while SDM is likely
to reduce net liability risks, it may increase providers' liability risks in
certain situations or with select patients. Overall, engaging in SDM should be
understood as clearly distinct from the process of obtaining IC and could reduce
clinicians' risk of liability when applied carefully and thoughtfully.
PMID- 27607575
TI - Omentin protects against LPS-induced ARDS through suppressing pulmonary
inflammation and promoting endothelial barrier via an Akt/eNOS-dependent
mechanism.
AB - Acute respiratory distress syndrome (ARDS) is characterized by increased
pulmonary inflammation and endothelial barrier permeability. Omentin has been
shown to benefit obesity-related systemic vascular diseases; however, its effects
on ARDS are unknown. In the present study, the level of circulating omentin in
patients with ARDS was assessed to appraise its clinical significance in ARDS.
Mice were subjected to systemic administration of adenoviral vector expressing
omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh
omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS.
Pulmonary endothelial cells (ECs) were treated with rh-omentin to further
investigate its underlying mechanism. We found that a decreased level of
circulating omentin negatively correlated with white blood cells and
procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced
ARDS by alleviating the pulmonary inflammatory response and endothelial barrier
injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of
pulmonary ECs with rh-omentin attenuated inflammatory response and restored
adherens junctions (AJs), and cytoskeleton organization promoted endothelial
barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC
survival and differentiation was blocked by the Akt/eNOS pathway inactivation.
Therapeutic rh-omentin treatment also effectively protected against LPS-induced
ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin
protects against LPS-induced ARDS by suppressing inflammation and promoting the
pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent
mechanism. Therapeutic strategies aiming to restore omentin levels may be
valuable for the prevention or treatment of ARDS.
PMID- 27607574
TI - Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect
in a Parkinson disease mouse model.
AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and
regeneration-promoting factor for dopaminergic neurons in cell and animal models
of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD
patients with so far inconclusive results. The receptor tyrosine kinase Ret is
the canonical GDNF receptor, but several alternative GDNF receptors have been
proposed, raising the question of which signaling receptor mediates here the
beneficial GDNF effects. To address this question we overexpressed GDNF in the
striatum of mice deficient for Ret in dopaminergic neurons and subsequently
challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Strikingly, in this established PD mouse model, the absence of Ret completely
abolished GDNF's neuroprotective and regenerative effect on the midbrain
dopaminergic system. This establishes Ret signaling as absolutely required for
GDNF's effects to prevent and compensate dopaminergic system degeneration and
suggests Ret activation as the primary target of GDNF therapy in PD.
PMID- 27607576
TI - Atg5-dependent autophagy contributes to the development of acute myeloid leukemia
in an MLL-AF9-driven mouse model.
AB - Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy
originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation
pathway that is hypothesized to be important for the maintenance of AML as well
as contribute to chemotherapy response. Here we employ a mouse model of AML
expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion,
a key autophagy protein, on the malignant transformation and progression of AML.
Consistent with a transient decrease in colony-forming potential in vitro, the in
vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary
transplantation prolonged the survival of recipient mice, suggesting that
autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion
of Atg5 in malignant AML cells during secondary transplantation did not influence
the survival or chemotherapeutic response of leukemic mice. Interestingly,
autophagy was found to be involved in the survival of differentiated myeloid
cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that
Atg5-dependent autophagy may contribute to the development but not chemotherapy
sensitivity of murine AML induced by MLL-AF9.
PMID- 27607577
TI - MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by
inhibiting FOXO3a.
AB - Cisplatin is widely used for chemotherapy of a variety of malignancies. However,
the clinical application of cisplatin is hampered by the resultant irreversible
hearing loss due to hair cell apoptosis. To date, no practical regimen to resolve
this has been developed. Meanwhile, the role of microRNA in protecting hair cells
from cisplatin-induced apoptosis in the inner ear has not been extensively
investigated. In this study, we monitored miR-183, -96, and -182 turnover in the
cochlea during cisplatin treatment in vitro. We found that overexpression of miR
182, but not miR-183 and -96, improved hair cell survival after 3 MUM cisplatin
treatment in vitro. We demonstrated that overexpression of miR-182 repressed the
intrinsic apoptotic pathway by inhibiting the translation of FOXO3a. Our study
offers a new therapeutic target for alleviating cisplatin-induced hair cell
apoptosis in a rapid and tissue-specific manner.
PMID- 27607578
TI - Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in
pulmonary inflammation following LPS.
AB - Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by
priming for an exaggerated response to a second infectious stimulus. Acute lung
injury (ALI) is a major component of multiple organ dysfunction syndrome
following HS and regularly serves as a major cause of patient mortality. The lung
vascular endothelium is an active organ that has a central role in the
development of ALI through synthesizing and releasing of a number of inflammatory
mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which
features rapid plasma membrane rupture and release of proinflammatory
intracellular contents. In this study, we demonstrated an important role of HS in
priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS
through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3)
inflammasome in mouse lung vascular EC, and subsequently induces caspase-1
activation. However, HS induced release of high-mobility group box 1 (HMGB1),
which acting through the receptor for advanced glycation end products initiates
EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events,
including cathepsin B release from ruptured lysosomes followed by pyroptosome
formation and caspase-1 activation. These HS-induced events enhance LPS-induced
EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly
exaggerates lung inflammation and injury. The present study explores a novel
mechanism underlying HS-primed ALI and thus presents a potential therapeutic
target for post-HS ALI.
PMID- 27607579
TI - Distal regulation of c-myb expression during IL-6-induced differentiation in
murine myeloid progenitor M1 cells.
AB - The c-Myb transcription factor is a major regulator that controls differentiation
and proliferation of hematopoietic progenitor cells, which is frequently
deregulated in hematological diseases, such as lymphoma and leukemia.
Understanding of the mechanisms regulating the transcription of c-myb gene is
challenging as it lacks a typical promoter and multiple factors are involved. Our
previous studies identified some distal regulatory elements in the upstream
regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed
mechanisms still remain unclear. In the present study, we found that a cell
differentiation-related DNase1 hypersensitive site is located at a -28k region
upstream of c-myb gene and that transcription factors Hoxa9, Meis1 and PU.1 bind
to the -28k region. Circular chromosome conformation capture (4C) assay confirmed
the interaction between the -28k region and the c-myb promoter, which is
supported by the enrichment of CTCF and Cohesin. Our analysis also points to a
critical role for Hoxa9 and PU.1 in distal regulation of c-myb expression in
murine myeloid cells and cell differentiation. Overexpression of Hoxa9 disrupted
the IL-6-induced differentiation of M1 cells and upregulated c-myb expression
through binding of the -28k region. Taken together, our results provide an
evidence for critical role of the -28k region in distal regulatory mechanism for
c-myb gene expression during differentiation of myeloid progenitor M1 cells.
PMID- 27607581
TI - Lipid-derived reactive aldehydes link oxidative stress to cell senescence.
PMID- 27607580
TI - Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS
mutated NSCLC to pro-apoptotic agents.
AB - Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related
death worldwide and a high medical need for more effective therapies. Small
molecule inhibitors of the bromodomain and extra terminal domain (BET) family
such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer
types, including lung cancer. Although their activity on oncogene expression such
as c-Myc has been addressed in many studies, the effects of BET inhibition on the
apoptotic pathway remain largely unknown. Here we evaluated the activity of BET
bromodomain inhibitors on cell cycle distribution and on components of the
apoptosis response. Using a panel of 12 KRAS-mutated NSCLC models, we found that
cell lines responsive to BET inhibitors underwent apoptosis and reduced their S
phase population, concomitant with downregulation of c-Myc expression.
Conversely, ectopic c-Myc overexpression rescued the anti-proliferative effect of
JQ1. In the H1373 xenograft model, treatment with JQ1 significantly reduced tumor
growth and downregulated the expression of c-Myc. The effects of BET inhibition
on the expression of 370 genes involved in apoptosis were compared in sensitive
and resistant cells and we found the expression of the two key apoptosis
regulators FLIP and XIAP to be highly BET dependent. Consistent with this,
combination treatment of JQ1 with the tumor necrosis factor-related apoptosis
inducing ligand (TRAIL) or the pro-apoptotic chemotherapeutic agent cisplatin
enhanced induction of apoptosis in both BET inhibitor sensitive and resistant
cells. Further we showed that combination of JQ1 with cisplatin led to
significantly improved anti-tumor efficacy in A549 tumor-bearing mice.
Altogether, these results show that the identification of BET-dependent genes
provides guidance for the choice of drug combinations in cancer treatment. They
also demonstrate that BET inhibition primes NSCLC cells for induction of
apoptosis and that a combination with pro-apoptotic compounds represents a
valuable strategy to overcome treatment resistance.
PMID- 27607582
TI - Clearance of autophagy-associated dying retinal pigment epithelial cells - a
possible source for inflammation in age-related macular degeneration.
AB - Retinal pigment epithelial (RPE) cells can undergo different forms of cell death,
including autophagy-associated cell death during age-related macular degeneration
(AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different
dying cells in the retina may result in the accumulation of debris and
progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy
associated cell death upon serum depletion and oxidative stress induced by
hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II
(LC3-II) expression and electron microscopy, while autophagic flux was confirmed
by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells.
The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs
and living RPE cells in an increasing and time-dependent manner. Inhibition of
autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy
associated dying cells by macrophages, whereas sorting out the GFP-LC3
positive/autophagic cell population or treatment by the glucocorticoid
triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released
when autophagy-associated dying RPEs were engulfed by macrophages. Our data
suggest that cells undergoing autophagy-associated cell death engage in clearance
mechanisms guided by professional and non-professional phagocytes, which is
accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.
PMID- 27607583
TI - Thrombospondin-1 signaling through CD47 inhibits cell cycle progression and
induces senescence in endothelial cells.
AB - CD47 signaling in endothelial cells has been shown to suppress angiogenesis, but
little is known about the link between CD47 and endothelial senescence. Herein,
we demonstrate that the thrombospondin-1 (TSP1)-CD47 signaling pathway is a major
mechanism for driving endothelial cell senescence. CD47 deficiency in endothelial
cells significantly improved their angiogenic function and attenuated their
replicative senescence. Lack of CD47 also suppresses activation of cell cycle
inhibitors and upregulates the expression of cell cycle promoters, leading to
increased cell cycle progression. Furthermore, TSP1 significantly accelerates
replicative senescence and associated cell cycle arrest in a CD47-dependent
manner. These findings demonstrate that TSP1-CD47 signaling is an important
mechanism driving endothelial cell senescence. Thus, TSP1 and CD47 provide
attractive molecular targets for treatment of aging-associated cardiovascular
dysfunction and diseases involving endothelial dysregulation.
PMID- 27607584
TI - Adipose-derived mesenchymal stem cells promote the survival of fat grafts via
crosstalk between the Nrf2 and TLR4 pathways.
AB - Autologous fat grafting is an effective reconstructive surgery technique;
however, its success is limited by inconsistent graft retention and an
environment characterized by high oxidative stress and inflammation. Adipose
derived stem cells (ADSCs) increase the survival of fat grafts, although the
underlying mechanisms remain unclear. Here, TLR4(-/-) and Nrf2(-/-) mice were
used to explore the effects of oxidative stress and inflammation on the viability
and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs
inhibited inflammatory cytokine production, enhanced growth factor levels,
increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4
expression, increased vascularization and reduced ROS production in a manner
dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related
factor 2 (Nrf2) expression. Immunohistochemical analysis showed that exposure to
hypoxia enhanced ADSC growth and promoted the differentiation of ADSCs into
vascular endothelial cells. Hypoxia-induced inflammatory cytokine, growth factor
and NOX1/4 upregulation, as well as increased ROS production and apoptosis in
ADSCs were dependent on TLR4 and Nrf2, which also modulated the effect of ADSCs
on promoting endothelial progenitor cell migration and angiogenesis. Western blot
analyses showed that the effects of hypoxia on ADSCs were regulated by crosstalk
between Nrf2 antioxidant responses and NF-kappaB- and TLR4-mediated inflammatory
responses. Taken together, our results indicate that ADSCs can increase the
survival of fat transplants through the modulation of inflammatory and oxidative
responses via Nrf2 and TLR4, suggesting potential strategies to improve the use
of ADSCs for cell therapy.
PMID- 27607586
TI - Sexual behaviors among women living with HIV in Ontario, Canada.
AB - Understanding the sexual activities and partnerships of women living with human
immunodeficiency virus (HIV) remains important to promote healthy sexuality and
to reduce the transmission of HIV and other sexually transmitted infections. We
described sexual behaviors of women living with HIV enrolled in an ongoing study
in Ontario, Canada. Data were available from 582 women who self-completed a
sexual behavior questionnaire between 2010 and 2012. Nearly half (46.1%) of women
reported a sexual partner in the preceding three months; women less likely to be
sexually active were older, Black/African, separated, divorced, widowed, single,
and unemployed. Most sexually active women had one partner (76.4%), a regular
partner (75.9%), male (96.2%) partner(s), and partners who were HIV-negative or
unknown HIV status (75.2%). Women were more likely to use a condom with HIV
negative/status unknown partners (81.3%) than with HIV-positive partners (58.6%;
p = .008). Only 8.0% of sexually active women reported condomless sex with a
discordant HIV-negative/status unknown partner when their viral load was
detectable. Overall, most women living with HIV were sexually inactive or engaged
in sexual activities that were low risk for HIV transmission.
PMID- 27607587
TI - Performance analysis in field hockey goalkeeping during penalty corners: a case
study.
AB - BACKGROUND: The purpose of this study is to investigate the kinematics of field
hockey goalkeeping during penalty corners, in order to provide the first model of
performance from a physical standpoint during this particular and important phase
of goalkeeping that goes from the injection of the ball (the push-in) up to the
shot on goal during a penalty corner. In particular, the focus was on the
preparation phase before the actual saves. METHODS: Four goalkeepers playing at
the international level (age: 22+/-2.45 years; height: 1.85+/-0.09 m; body
weight: 79.25+/-8.42 kg; BMI: 23.06+/-0.69 kg/m2; role experience 11.5+/-1.91
years; international caps: 30.00+/-15.25) participated in the study. A complete
video footage was recorded using two high-speed video cameras, using 210 fps
sampling rates. RESULTS: The goalkeepers covered 1.48+/-0.32 m, using 3.23+/-0.43
steps, from the goal line in about 1.33+/-0.21 s. The estimated mean acceleration
was 0.93+/-0.54 m/s2. Differences in these parameters were found among the
goalkeepers (one-way ANOVA; P<0.05, ES as partial eta2>0.14), also demonstrating
a different technical efficiency in relation to the task to be performed.
CONCLUSIONS: The results of this case study confirm that the principal aim of the
goalkeepers during the preparation phase of defending penalty corners is to
arrive in the best position of readiness within the available time frame of about
1.5 s. They ran out from the goal line about 1.5 m, not reaching an ideal better
distance (~4 m), for tactical reasons, concerning the possible interventions of
other attackers arriving close to the posts, to enlarge the goalmouth.
PMID- 27607588
TI - The effect of Pilates exercise on body composition in sedentary overweight and
obese women.
AB - BACKGROUND: Pilates is a popular exercise approach among women. Still there is
poor empirical quantitative evidence indicating a positive effect of Pilates
exercises on body composition. The aim of our study is to determine the effects
of Pilates exercises on body composition in sedentary overweight and obese women.
METHODS: Thirty-seven women, aged between 30 to 50 (43.79+/-4.88) years, included
the study. Subjects are randomly divided into Pilates group (N.=19) and control
group (N.=18). Pilates exercises was given for 90 minutes, 3 times/week, for 8
week with a gradual strength increase of 11-17 in the Rating of Perceived
Exercise. Control group did not participate in any physical activity program.
Bioelectric Impedance Analysis was used for determine the body composition of
participants. Weight, Body Mass Index (BMI), body fat mass, lean body mass,
waist, abdomen and hip circumference were measured at pre- and post-training
period. RESULTS: In Pilates group, weight, BMI, fat percentage, waist, abdomen
and hip circumference decreased significantly after training (P<0.05) while no
significant difference was observed in lean body mass (P>0.05). In control group,
abdomen and hip circumference increased significantly (P<0.05) as the other
parameters showed the tendency for an increase, but no significant difference
(P<0.05). CONCLUSIONS: The results of this study indicate that 8 weeks Pilates
exercises have positive effects on body composition in sedentary overweight and
obese women. Pilates exercises can be applied for improving body composition.
PMID- 27607585
TI - Exploratory analysis of ERCC2 DNA methylation in survival among pediatric
medulloblastoma patients.
AB - AIM: Medulloblastoma is the most frequent malignant pediatric brain tumor. While
survival rates have improved due to multimodal treatment including cisplatin
based chemotherapy, there are few prognostic factors for adverse treatment
outcomes. Notably, genes involved in the nucleotide excision repair pathway,
including ERCC2, have been implicated in cisplatin sensitivity in other cancers.
Therefore, this study evaluated the role of ERCC2 DNA methylation profiles on
pediatric medulloblastoma survival. METHODS: The study population included 71
medulloblastoma patients (age <18years at diagnosis) and recruited from Texas
Children's Cancer Center between 2004 and 2009. DNA methylation profiles were
generated from peripheral blood samples using the Illumina Infinium Human
Methylation 450 Beadchip. Sixteen ERCC2-associated CpG sites were evaluated in
this analysis. Multivariable regression models were used to determine the
adjusted association between DNA methylation and survival. Cox regression and
Kaplan-Meier curves were used to compare 5-year overall survival between hyper-
and hypo-methylation at each CpG site. RESULTS: In total, 12.7% (n=9) of the
patient population died within five years of diagnosis. In our population,
methylation of the cg02257300 probe (Hazard Ratio=9.33; 95% Confidence Interval:
1.17-74.64) was associated with death (log-rank p=0.01). This association
remained suggestive after correcting for multiple comparisons (FDR p<0.2). No
other ERCC2-associated CpG site was associated with survival in this population
of pediatric medulloblastoma patients. CONCLUSION: These findings provide the
first evidence that DNA methylation within the promoter region of the ERCC2 gene
may be associated with survival in pediatric medulloblastoma. If confirmed in
future studies, this information may lead to improved risk stratification or
promote the development of novel, targeted therapeutics.
PMID- 27607589
TI - Effectiveness of a new cervical pillow on pain and sleep quality in recreational
athletes with chronic mechanical neck pain: a preliminary comparative study.
AB - BACKGROUND: The aim of this intervention study was to determine the effects of a
new experimental cervical pillow, on symptomatic adults affected by chronic
mechanical neck pain. METHODS: Twelve recreational athletes of both sexes (mean
age 40.5 years; range 35-55), affected by grade II chronic mechanical neck pain,
were evaluated with a daily diary type of self-report questionnaire, which
incorporated an 11-point Numerical Rating Pain Scale, to collect the primary
outcome measures of pre- and post-sleep neck pain and with the Neck Pain
Disability Scale. Tympanic temperature, heart rate (HR) variability continuous
monitoring during sleep, overnight pillow comfort and sleep quality were
assessed. RESULTS: Average weekly scores in overall questionnaires, tympanic
temperature and the HR low frequency (LF) / high frequency (HF) ratio were
significantly lower (P<0.05) after the use of the DM2 pillow than the own pillow.
The 80% of participants considered the DM2 "perfectly comfortable" and reported a
"good" quality of sleep lying over it. CONCLUSIONS: The use of an appropriate
pillow is a determinant factor in relieving neck pain, improving LF/HF ratio and
enhancing-vagal activity, promoting deeper stages during the sleep. The shape of
this pillow maintains an appropriate cervical curvature, reduces intra-disc
pressure allowing a better distribution of loads between cervical discs. The
round shaped portion of the pillow, facilitates breathing and avoids the
narrowing of the airway due to the incorrect position during the sleep. The
peculiar material of the DM2 pillow, contributed to lower brain temperature
promoting dry heat loss from the head to the pillow, reducing sweating.
PMID- 27607590
TI - Changes in the heart rate recovery to endurance effort after high intensity
interval, strength, and concurrent exercise training in patients with insulin
resistance.
AB - BACKGROUND: The aim of this study was to assess the effects of three exercise
training programs in the adaptation of the heart rate recovery of patients with
insulin resistance. METHODS: We studied 43 women with insulin resistance, which
were assigned to three training groups: 1) high intensity interval training (HIT,
age 39.0+/-10 years); 2) strength training (ST, age 33.9+/-9.4 years); 3) HIT+ST
(MIXT, age 43.3+/-8.1 years); and 4) control group (CG, age 40.1+/-11 years).
Heart rate was measured at rest (HRrest), during the 2-km-walking-test (UKKT) for
mean (HRDE), and maximum (HRMDE) values, and during the recovery at one, two, and
three minutes after the UKKT. Additionally, anthropometric measurements (body
mass and body mass index) were assessed. RESULTS: HIT significantly decreased
HRrest and HRDE (-4.5% and -2% respectively, P<0.05). MIXT training also
decreased HRDE in -3% whilst both average and maximal HR during UKK were
significantly increased in the control group HRDE (+2% and +3% respectively).
Moreover, there were significant reductions in HR recovery at 1, 2 and 3 minutes
after both HIT and MIXT training, whereas these values were increased in control
group. CONCLUSIONS: Our findings suggest that HIT induces meaningful
cardiovascular adaptations in patient with insulin resistance, reducing heart
rate at rest, as well as during and after exercise, and that complementary
strength training increases these adaptations.
PMID- 27607591
TI - Therapeutic vaccines and immunological intervention in HIV infection: a paradigm
change.
AB - PURPOSE OF REVIEW: The purpose is to review current knowledge of immunological
interventions in HIV infection and discuss strategies for the establishment of
functional cure and/or HIV eradication. RECENT FINDINGS: Therapeutic vaccines and
cytokines have been historically the immunological interventions developed with
the objective to enhance the HIV-specific cell-mediated immune responses and to
suppress virus replication. Both these interventions have shown only partial
antiviral effects. The recent identification and generation of human broad
neutralizing antibodies provides potent immunological intervention associated
with effective suppression of virus replication in the absence of antiretroviral
therapy. Furthermore, the identification that the major HIV cell reservoir
containing replication competent and infectious virus is composed by programed
cell death protein 1 (PD-1) positive memory CD4 T cells offers the opportunity to
target directly the HIV cell reservoir with anti-PD-1 antibodies. Anti-PD-1
antibody therapy may be also critical to prevent exhaustion of CD8 T cells.
SUMMARY: The availability of a diverse armamentarium of immunological
intervention offers the opportunity to investigate the efficacy of the combined
use of different immunological interventions in inducing prolonged virus
suppression in the absence of antiretroviral therapy and functional cure HIV or
HIV eradication.
PMID- 27607594
TI - Adjuvants for HIV vaccines.
AB - PURPOSE OF REVIEW: Advances in the understanding of the structural biology of HIV
1 proteins, and in the vulnerabilities of HIV-1 at various points in the
infectious process have led to innovative approaches for vaccine constructs for
clinical trials. Lessons from the successful Retrovirology study 144 (RV144)
phase III Thai trial have revealed the need for novel and more potent adjuvant
formulations. Fortunately, the vaccine adjuvant field is experiencing an
emergence of innovative new adjuvants and strategies that may lead to improved
formulations. RECENT FINDINGS: The review highlights the status of currently used
and available new adjuvant formulations for HIV antigens. Adjuvants used in
preclinical or in human clinical trials using HIV-1 protein antigens will be
discussed along with adjuvant improvements for vectors and DNA immunization.
SUMMARY: The HIV-1 immunogen and the design of the adjuvant formulations are both
equally important for the development of an effective HIV vaccine. Adjuvants work
by numerous different mechanisms, many of which are quite complex and often not
well comprehended. Understanding the interplay of innate and adaptive immune
responses that can be harnessed by adjuvant formulations would aid in the
rational design of a well tolerated and effective vaccine formulation that can
block HIV at the site of transmission.
PMID- 27607592
TI - Cancer therapies in HIV cure research.
AB - PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in
various stages of clinical development as potential interventions to target HIV
persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been
investigated in vitro, ex vivo and in clinical trials as interventions aimed at
reversing HIV latency and depleting the amount of virus that persists on
antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV
expression in patients on antiretroviral therapy but did not reduce the frequency
of infected cells. Other interventions that may accelerate the decay of latently
infected cells, in the presence or absence of latency-reversing therapy, are now
being explored. These include apoptosis-promoting agents, nonhistone deacetylase
inhibitor compounds to reverse HIV latency and immunotherapy interventions to
enhance antiviral immunity such as immune checkpoint inhibitors and Toll-like
receptor agonists. SUMMARY: A curative strategy in HIV will likely need to both
reduce the amount of virus that persists on antiretroviral therapy and improve
anti-HIV immune surveillance. Although we continue to explore advances in the
field of oncology including cancer immunotherapy, there are major differences in
the risk-benefit assessment between HIV-infected individuals and patients with
malignancies. Drug development specifically targeting HIV persistence will be the
key to developing effective interventions with an appropriate safety profile.
PMID- 27607593
TI - HIV-associated malignancies in sub-Saharan Africa: progress, challenges, and
opportunities.
AB - PURPOSE OF REVIEW: To summarize recent developments for HIV-associated
malignancies (HIVAM) in low-income and middle-income countries (LMIC) with
particular focus on sub-Saharan Africa (SSA). RECENT FINDINGS: Antiretroviral
therapy (ART) scale-up is leading to epidemiologic transitions in LMIC similar to
high-income countries, with aging and growth of HIV-infected populations,
declining infectious deaths, increasing cancer deaths, and transitions from AIDS
defining cancers to non-AIDS defining cancers. Despite ART scale-up, the HIVAM
burden remains high including an enormous AIDS-defining cancers burden in SSA.
For Kaposi sarcoma, patients treated with ART and chemotherapy can experience
good outcomes even in rural SSA, but Kaposi sarcoma heterogeneity remains
insufficiently understood including virologic, immunologic, and inflammatory
features that may be unique to LMIC. For cervical cancer, scale-up of prevention
efforts including vaccination and screening is underway, with benefits already
apparent despite continuing high disease burden. For non-Hodgkin lymphoma,
curative treatment is possible in the ART era even in SSA, and multifaceted
approaches can improve outcomes further. For many other prevalent HIVAM, care and
research efforts are being established to guide treatment and prevention
specifically in LMIC. SUMMARY: Sustained investment for HIVAM in LMIC can help
catalyze a cancer care and research agenda that benefits HIV-positive and HIV
negative patients worldwide.
PMID- 27607595
TI - HIV vaccines moving forward.
PMID- 27607597
TI - Biofouling potential and material reactivity in a simulated water distribution
network supplied with stormwater recycled via managed aquifer recharge.
AB - The injection of stormwater into aquifers for storage and recovery during high
water demand periods is a promising technology for augmenting conventional water
reserves. Limited information exists regarding the potential impact of aquifer
treated stormwater in distribution system infrastructure. This study describes a
one year pilot distribution pipe network trial to determine the biofouling
potential for cement, copper and polyvinyl chloride pipe materials exposed to
stormwater stored in a limestone aquifer compared to an identical drinking water
rig. Median alkalinity (123 mg/L) and colour (12 HU) in stormwater was
significantly higher than in drinking water (82 mg/L and 1 HU) and pipe
discolouration was more evident for stormwater samples. X-ray Diffraction and
Fluorescence analyses confirmed this was driven by the presence of iron rich
amorphous compounds in more thickly deposited sediments also consistent with
significantly higher median levels of iron (~0.56 mg/L) in stormwater compared to
drinking water (~0.17 mg/L). Water type did not influence biofilm development as
determined by microbial density but faecal indicators were significantly higher
for polyvinyl chloride and cement exposed to stormwater. Treatment to remove iron
through aeration and filtration would reduce the potential for sediment
accumulation. Operational and verification monitoring parameters to manage
scaling, corrosion, colour, turbidity and microbial growth in recycled stormwater
distribution networks are discussed.
PMID- 27607598
TI - Practice patterns in the diagnosis of inherited platelet disorders within a
single institution.
AB - : The diagnosis of inherited platelet disorders (IPDs) is challenging with
variable diagnostic practices existing between institutions. To determine
patterns and utility of diagnostic testing practices for IPDs within a single
institution, a retrospective cohort study was performed. Records of 50 patients
(50% women), median age 32 years (1 day to 81 years) were analyzed. In total, 28
(53%) had a positive International Society of Thrombosis and Hemostasis Bleeding
Assessment Tool score. Test-ordering patterns were highly variable. All patients
had platelet morphology analysis by light microscopy. In total, 42 (84%)
underwent light transmission aggregometry, 43 (86%) platelet function analyzer,
37 (74%) platelet electron microscopy, 25 (50%) flow cytometry, and 15 (30%)
genetic testing. Platelet function analyzer and light transmission aggregometry
were always used as first-order tests, followed by platelet transmission electron
microscopy and flow cytometry (81 and 84%, respectively). Genetic testing was
obtained up front in five cases (33% of orders), mostly in patients with
syndromic thrombocytopenia or in the setting of a known genetic disorder. Test
ordering practices did not adhere to published algorithms. Even within a single
institution, great heterogeneity exists in the testing approach to IPDs.
Although, a large proportion of cases were studied with platelet transmission
electron microscopy and flow cytometry, standard platelet assays established the
diagnosis in a great majority. Standardization of testing practices, first
beginning at the institutional level is a much needed step forward.
PMID- 27607596
TI - Lung cancer in persons with HIV.
AB - PURPOSE OF REVIEW: Lung cancer is emerging as a leading cause of death in HIV
infected persons. This review will discuss the latest scientific evidence
regarding the mechanisms driving lung cancer risk in HIV infection, the clinical
presentation of lung cancer in HIV-infected persons and recent data regarding the
outcomes, treatment and prevention of lung cancer in this group. RECENT FINDINGS:
Increased risk of lung cancer in HIV-infected persons is primarily due to higher
smoking rates, but emerging evidence also implicates immunosuppression and
inflammatory processes. Lung cancer outcomes may be worse in HIV-infected persons
in the antiretroviral era, but this may stem, in part, from treatment
disparities. Early detection of lung cancer using chest computed tomography (CT)
is being increasingly adopted for smokers in the general population, and recent
studies suggest that it may be safe and efficacious in HIV-infected smokers.
SUMMARY: Lung cancer is an important complication associated with chronic HIV
infection. It is associated with unique HIV-related causal mechanisms, and may be
associated with worse outcomes in some HIV-infected persons. Smoking cessation
and early cancer detection with chest CT are likely to benefit HIV-infected
smokers.
PMID- 27607599
TI - Temporal changes in clot lysis and clot stability following tranexamic acid in
cardiac surgery.
AB - : Cardiac surgery induces a multifactorial coagulopathy. Regular use of
tranexamic acid (TXA) is becoming standard of care. Clinical challenges include
selecting optimal dosing regimen and balancing the benefit versus risk of
additional dosing with antifibrinolytics. The objective was to evaluate the
effect of TXA by assessing kinetic properties of plasma clot formation, clot
stability, and clot fibrinolysis. The study was a prospective case follow-up of
28 patients undergoing cardiac surgery (mean age 63.9 years, 29% women). Blood
samples were analysed at seven time points during the first 48 h after surgery.
All patients were treated with TXA, 2 g at start surgery, 1 g during extra
corporeal circulation, and 1 g after reversal of heparin. An automated clot lysis
assay using tissue factor and tissue plasminogen activator (tPA) was performed to
evaluate clot formation, stability, and fibrinolysis. TXA protects against
facilitated fibrinolysis and induces up to 13-fold increase in clot stability.
All patients showed complete resistance to tPA-induced fibrinolysis during the
first 6 h after cardiac surgery declining to 33% of patients at 48 h. Impaired
renal function was associated with prolonged resistance to tPA-induced
fibrinolysis. Despite inhibition of fibrinolysis with TXA, the overall clot
stability declines and the kinetic properties of clot formation were impaired
after cardiac surgery. TXA induces a multifold increase in clot resistance to
fibrinolysis but does not affect clot formation or clot stability. Monitoring the
level of resistance to fibrinolysis may prevent overdosing in particular in
patients with impaired renal function.
PMID- 27607601
TI - Correction to The Nuclease Domain of the Escherichia Coli RecBCD Enzyme Catalyzes
Degradation of Linear and Circular Single-Stranded and Double-Stranded DNA.
PMID- 27607600
TI - Association Study Between Promoter Polymorphisms of ADAM17 and Progression of
Sepsis.
AB - BACKGROUND: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to
play a significant role in the pathogenesis of sepsis. However, little is known
about the clinical relevance of ADAM17 polymorphisms to sepsis onset and
development. METHODS: This study analyzed the associations of five ADAM17
promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and
rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was
performed using pyrosequencing and polymerase chain reaction-length polymorphism
method. The ADAM17 expression was measured using the real-time PCR method and the
concentrations of related cytokines were detected using enzyme-linked
immunosorbent assay. RESULTS: No associations were observed between these
polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were
overrepresented among the patients with severe sepsis (P=0.002) or septic shock
(P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role
of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was
increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied
by up-regulation of expression of the ADAM17 substrates (TNF-alpha, IL-6R and
CX3CL1) and pro-inflammatory cytokines (IL-1beta and IL-6). CONCLUSION: The
present study has provided potentially valuable clinical evidence that the ADAM17
rs12692386 polymorphism is a functional variant that might be used as a relevant
risk estimate for the progression of sepsis.
PMID- 27607602
TI - A pressure ulcer and fall rate quality composite index for acute care units: A
measure development study.
AB - BACKGROUND: Composite indices are single measures that combine the strengths of
two or more individual measures and provide broader, easy-to-use measures for
evaluation of provider performance and comparisons across units and hospitals to
support quality improvement. OBJECTIVE: The study objective was to develop a unit
level inpatient composite nursing care quality performance index-the Pressure
Ulcer and Fall Rate Quality Composite Index. DESIGN: Two-phase measure
development study. SETTINGS: 5144 patient care units in 857 United States
hospitals participating in the National Database of Nursing Quality Indictors(r)
during the year 2013. METHODS: The Pressure Ulcer and Fall Rate Quality Composite
Index was developed in two phases. In Phase 1 the formula was generated using a
utility function and generalized penalty analysis. Experts with experience in
healthcare quality measurement provided the point of indicator equivalence. In
Phase 2 initial validity evidence was gathered based on hypothesized
relationships between the Pressure Ulcer and Fall Rate Quality Composite Index
and other variables using two-level (unit, hospital) hierarchical linear mixed
modeling. RESULTS: The Pressure Ulcer and Fall Rate Quality Composite Index=100
PUR-FR, where PUR is pressure ulcer rate and FR is total fall rate. Higher scores
indicate better quality. Bland-Altman plots demonstrated agreement between pairs
of experts and provided evidence for inter-rater reliability of the formula. The
validation process demonstrated that higher registered nurse skill mix, higher
percent of registered nurses with a baccalaureate in nursing or higher degree,
higher percent of registered nurses with national specialty certification, and
lower percent of hours supplied by agency staff were significantly associated
with higher Pressure Ulcer and Fall Rate Quality Composite Index scores. Higher
percentages of unit patients at risk for a hospital-acquired pressure ulcer and
higher unit rates of physical restraint use were not associated with higher
Pressure Ulcer and Fall Rate Quality Composite Index scores. CONCLUSIONS: The
Pressure Ulcer and Fall Rate Quality Composite Index is a step toward providing a
more holistic perspective of unit level nursing quality than individual measures
and may help nurses nursing administrators obtain a broader view of which patient
care units are the higher and lower performers. Further study is needed to
examine the usability of the Pressure Ulcer and Fall Rate Quality Composite
Index.
PMID- 27607603
TI - Vascular network tightly enclosing lesions of molluscum contagiosum: Basket-like
capillaries of molluscum.
AB - Immunohistochemical studies of one typical and two atypical cases of molluscum
contagiosum with anti-CD34 monoclonal antibodies showed a tightly enclosing fine
vasculature around the lesional masses of the disease. The thin interstitial
septa between the lobules of the molluscum lesions also contained abundant
endothelium. An electron microscopic study of a pinched-off lesion of common
molluscum contagiosum demonstrated that the tightly enclosing blood vessels
lacked muscle layers, suggesting that they were capillaries, being a distance of
several hundred nanometers from the basal cells of the molluscum mass. A 3D
constructed image of the vasculature confirmed a network of the vessels. These
tightly enclosing vascular networks around the lesions of molluscum contagiosum
support the rapid growth of this disease.
PMID- 27607604
TI - Population genetic structure of cotton pink bollworm, Pectinophora gossypiella
(Saunders) (Lepidoptera: Gelechiidae) using mitochondrial cytochrome oxidase I
(COI) gene sequences from India.
AB - Pink bollworm (PBW), Pectinophora gossypiella is one of the most destructive
pest's globally inflicting huge economic losses in cotton even during later
stages of crop growth. In the present investigation, the population genetic
structure, distribution, and genetic diversity of P. gossypiella in cotton
growing zones of India using partial mitochondrial DNA cytochrome oxidase-I (COI)
gene was addressed. The overall haplotype (Hd), number of nucleotide differences
(K), and nucleotide diversity (pi) were 0.3028, 0.327, and 0.00047, respectively
which suggest that entire population exhibited low level of genetic diversity.
Zone-wise clustering of population revealed that central zone recorded low level
of Hd (0.2730) as compared to north (0.3619) and south (0.3028) zones. The most
common haplotype (H1) reported in all 19 locations could be proposed as
ancestral/original haplotype. This haplotype with one mutational step formed star
like phylogeny connected with 11 other haplotypes. The phylogenetic relationship
studies revealed that most haplotypes of populations are closely related to each
other. Haplotype 5 was exclusively present in Dharwad (South zone) shared with
populations of Hanumangarh and Bathinda (North zone). The result indicated that
there is no isolation by distance effect among the Indian populations of PBW. The
present study reports a low genetic diversity among PBW populations of India and
H1, as ancestral haplotype from which other haplotypes have evolved suggests that
the migration and dispersal over long distance and invasiveness are major
factors.
PMID- 27607606
TI - In vivo assessment by parents and a physician using the Amsterdam Infant Stool
Scale provided better inter-rater agreement than photographic evaluation.
AB - AIM: This study assessed the inter-rater variability of stool assessment,
comparing the judgement of parents and a physician using the Amsterdam Infant
Stool Scale (AISS) and the evaluation by another physician using photographs.
METHODS: The stools of children aged two to 18 months, who were not toilet
trained, were independently assessed in vivo using the AISS by the parents and
the first physician. Another physician, unaware of the results of the in vivo
evaluation, assessed two stool photographs taken by the first physician with a
smartphone. RESULTS: Having analysed 100 stools, we found excellent inter-rater
agreement between the parents and the first physician for consistency (kappa:
0.87; 95% confidence interval [95% CI] 0.78-0.95) and colour (kappa: 0.81; 95%
CI: 0.71-0.91) and good inter-rater agreement for the amount (kappa: 0.79; 95% CI
0.7-0.88). We found moderate inter-rater agreement between the parents' in vivo
assessment and the second physician's photographic assessment for stool
consistency (kappa: 0.5; 95% CI 0.36-0.64) and amount (kappa: 0.44; 95% CI 0.29
0.59) and a fair inter-rater agreement for colour (kappa: 0.33; 95% CI 0.21
0.45). CONCLUSION: When parents and a physician used the AISS under in vivo
conditions, there was better inter-rater agreement than photographic evaluation
by a second physician.
PMID- 27607605
TI - Role of Class III phosphoinositide 3-kinase in the brain development: possible
involvement in specific learning disorders.
AB - Class III phosphoinositide 3-kinase (PIK3C3 or mammalian vacuolar protein sorting
34 homolog, Vps34) regulates vesicular trafficking, autophagy, and nutrient
sensing. Recently, we reported that PIK3C3 is expressed in mouse cerebral cortex
throughout the developmental process, especially at early embryonic stage. We
thus examined the role of PIK3C3 in the development of the mouse cerebral cortex.
Acute silencing of PIK3C3 with in utero electroporation method caused positional
defects of excitatory neurons during corticogenesis. Time-lapse imaging revealed
that the abnormal positioning was at least partially because of the reduced
migration velocity. When PIK3C3 was silenced in cortical neurons in one
hemisphere, axon extension to the contralateral hemisphere was also delayed.
These aberrant phenotypes were rescued by RNAi-resistant PIK3C3. Notably,
knockdown of PIK3C3 did not affect the cell cycle of neuronal progenitors and
stem cells at the ventricular zone. Taken together, PIK3C3 was thought to play a
crucial role in corticogenesis through the regulation of excitatory neuron
migration and axon extension. Meanwhile, when we performed comparative genomic
hybridization on a patient with specific learning disorders, a 107 Kb-deletion
was identified on 18q12.3 (nt. 39554147-39661206) that encompasses exons 5-23 of
PIK3C3. Notably, the above aberrant migration and axon growth phenotypes were not
rescued by the disease-related truncation mutant (172 amino acids) lacking the C
terminal kinase domain. Thus, functional defects of PIK3C3 might impair
corticogenesis and relate to the pathophysiology of specific learning disorders
and other neurodevelopmental disorders. Acute knockdown of Class III
phosphoinositide 3-kinase (PIK3C3) evokes migration defects of excitatory neurons
during corticogenesis. PIK3C3-knockdown also disrupts axon outgrowth, but not
progenitor proliferation in vivo. Involvement of PIK3C3 in neurodevelopmental
disorders might be an interesting future subject since a deletion mutation in
PIK3C3 was detected in a patient with specific learning disorders (SLD).
PMID- 27607607
TI - Femtosecond laser-induced hard X-ray generation in air from a solution flow of Au
nano-sphere suspension using an automatic positioning system.
AB - Femtosecond laser-induced hard X-ray generation in air from a 100-um-thick
solution film of distilled water or Au nano-sphere suspension was carried out by
using a newly-developed automatic positioning system with 1-um precision. By
positioning the solution film for the highest X-ray intensity, the optimum
position shifted upstream as the laser power increased due to breakdown.
Optimized positioning allowed us to control X-ray intensity with high fidelity. X
ray generation from Au nano-sphere suspension and distilled water showed
different power scaling. Linear and nonlinear absorption mechanism are analyzed
together with numerical modeling of light delivery.
PMID- 27607608
TI - Enhanced near-infrared absorption in graphene with multilayer metal-dielectric
metal nanostructure.
AB - A multilayer metal-dielectric-metal nanostructure is proposed to enhance the
absorption in graphene in a near-infrared region. The main feature of the
structure is the generation of strong magnetic response within the dielectric
spacer, which is directly related to absorption enhancement in graphene to over
22 times higher than that of free-standing monolayer graphene. We also show that
absorption enhancement in graphene can be easily controlled by adjusting the
geometry of the propose structure. The simple structural configuration and the
flexible tunability in absorption enhancement are beneficial for practical
fabrication and future applications in graphene-based active optoelectronic
devices.
PMID- 27607609
TI - Ultrahigh-brightness, spectrally-flat, short-wave infrared supercontinuum source
for long-range atmospheric applications.
AB - Fiber based supercontinuum (SC) sources with output spectra covering the infrared
atmospheric window are very useful in long-range atmospheric applications. It is
proven that silica fibers can support the generation of broadband SC sources
ranging from the visible to the short-wave infrared region. In this paper, we
present the generation of an ultrahigh-brightness spectrally-flat 2-2.5 MUm SC
source in a cladding pumped thulium-doped fiber amplifier (TDFA) numerically and
experimentally. The underlying physical mechanisms behind the SC generation
process are investigated firstly with a numerical model which includes the fiber
gain and loss, the dispersive and nonlinear effects. Simulation results show that
abundant soliton pulses are generated in the TDFA, and they are shifted towards
the long wavelength side very quickly with the nonlinearity of Raman soliton self
frequency shift (SSFS), and eventually the Raman SSFS process is halted due to
the silica fiber's infrared loss. A spectrally-flat 2-2.5 MUm SC source could be
generated as the result of the spectral superposition of these abundant soliton
pulses. These simulation results correspond qualitatively well to the following
experimental results. Then, in the experiment, a cladding pumped large-mode-area
TDFA is built for pursuing a high-power 2-2.5 MUm SC source. By enhancing the
pump strength, the output SC spectrum broadens to the long wavelength side
gradually. At the highest pump power, the obtained SC source has a maximum
average power of 203.4 W with a power conversion efficiency of 38.7%. It has a 3
dB spectral bandwidth of 545 nm ranging from 1990 to 2535 nm, indicating a power
spectral density in excess of 370 mW/nm. Meanwhile, the output SC source has a
good beam profile. This SC source, to the best of our knowledge, is the brightest
spectrally-flat 2-2.5 MUm light source ever reported. It will be highly desirable
in a lot of long-range atmospheric applications, such as broad-spectrum LIDAR,
free space communication and hyper-spectral imaging.
PMID- 27607610
TI - Symmetry breaking induced excitations of dark plasmonic modes in multilayer
graphene ribbons.
AB - Multilayer graphene can support multiple plasmon bands. If structured into
graphene ribbons, they can support multiple localized plasmonic modes with
interesting optical properties. However, not all such plasmonic modes can be
excited directly due to the constrains of the structural symmetry. We show by
numerical simulations that by breaking the symmetry all plasmonic modes can be
excited. We discuss the general principles and properties of two-layer graphene
ribbons and then extend to multilayer graphene ribbons. In multilayer graphene
ribbons with different ribbon widths, a tunable broadband absorption can be
attained due to the excitations of all plasmonic modes. Our results suggest that
these symmetry-broken multilayer graphene ribbons could offer more degrees of
freedom in designing photonic devices.
PMID- 27607611
TI - Realization of the single photon Talbot effect with a spatial light modulator.
AB - We demonstrate the quantum Talbot effect using a beam of single photons produced
by parametric down conversion. In contrast to the previous works, we use a
programmable spatial light modulator to behave as a diffraction grating. Thus,
the investigation of the Talbot diffraction patterns under the variation of
grating structure can be easily performed. The influence of spectral bandwidth of
the down-converted photons on the diffraction pattern is also investigated. A
theoretical model based on the wave nature of photons is presented to explain the
Talbot diffraction patterns under varying conditions. The measured diffraction
patterns are in good agreement with the theoretical prediction. We are convinced
that our study improves the understanding of the quantum Talbot effect.
PMID- 27607612
TI - Mechanical squeezing and photonic anti-bunching in a coupled two-cavity
optomechanical system.
AB - We propose a scheme for generating the squeezing of a mechanical mode and the
anti-bunching of photonic modes in an optomechanical system. In this system,
there are two photonic modes (the left cavity-mode and the right cavity-mode) and
one mechanical mode. Both the left cavity-mode and the right cavity-mode are
driven by two lasers, respectively. The power of the driving lasers and the
detuning between them play a key role in generating squeezing of the mechanical
mode. We find that the squeezing of the mechanical mode can be achieved even at a
high temperature by increasing the power of the driving lasers. We also find that
the cavity-modes can show photonic anti-bunching under suitable conditions.
PMID- 27607613
TI - Circadian-effect engineering of solid-state lighting spectra for beneficial and
tunable lighting.
AB - Optimization of solid-state lighting spectra is performed to achieve beneficial
and tunable circadian effects. First, the minimum spectral circadian action
factor (CAF) of 2700 K white light-emitting diodes (LEDs) is studied for
applications where biologically active illumination is undesirable. It is found
that white-LEDs based on (i) RGB chips, (ii) blue & red chips plus green
phosphor, and (iii) blue chip plus green & red phosphors are the corresponding
minimum-CAF solutions at color-rendering index (CRI) requirements of 80, 90, and
95, respectively. Second, maximum CAF tunability of LED clusters is studied for
dynamic daylighting applications. A dichromatic phosphor-converted blue-centered
LED, a dichromatic phosphor-converted green-centered LED, and a monochromatic red
LED are grouped to obtain white spectra between 2700 K and 6500 K. A maximum CAF
tunability of 3.25 times is achieved with CRI above 90 and luminous efficacy of
radiation of 313 - 373 lm/W. We show that our approaches have advantages over
previously reported solutions on system simplicity, minimum achievable CAF value,
CAF tunability range, and light source efficacy.
PMID- 27607614
TI - Introduction to the Feature Issue on nanophotonics.
AB - This feature issue is a partial collection of contributions from authors who
presented their research at the 9th International Conference on Nanophotonics
(ICNP 2016) held during March 21-25, 2016 at Academia Sinica, Taipei, Taiwan.
ICNP is an independent conference series dedicated to nanophotonics research and
applications. This feature issue collects 28 papers related to research presented
at ICNP 2016.
PMID- 27607615
TI - Trapping metallic particles under resonant wavelength with 4pi tight focusing of
radially polarized beam.
AB - Here we propose a new method for trapping the resonant metallic particles with
the 4pi tight focusing (high numerical-aperture (NA)) system, which is
illuminated by radial polarization light. Numerical simulations have indicated
the maximum total optical force is 16.1pN while with nearly zero scattering force
under axis trapping, which keeps the gradient force predominant. Furthermore, the
distribution of total force is centrosymmetric and odd. We also gain stable 3D
trap with an equilibrium point along z axis and r axis as in normal optical
tweezers. What's more, we obtain the nearly pure longitudinal field. The maximum
transverse intensity is only 2.3 * 10-3 and the transverse spot size
reaches 0.36lambda, which is below Abbe's diffraction limit.
PMID- 27607616
TI - Denoised Wigner distribution deconvolution via low-rank matrix completion.
AB - Wigner distribution deconvolution (WDD) is a decades-old method for recovering
phase from intensity measurements. Although the technique offers an elegant
linear solution to the quadratic phase retrieval problem, it has seen limited
adoption due to its high computational/memory requirements and the fact that the
technique often exhibits high noise sensitivity. Here, we propose a method for
noise suppression in WDD via low-rank noisy matrix completion. Our technique
exploits the redundancy of an object's phase space to denoise its WDD
reconstruction. We show in model calculations that our technique outperforms
other WDD algorithms as well as modern iterative methods for phase retrieval such
as ptychography. Our results suggest that a class of phase retrieval techniques
relying on regularized direct inversion of ptychographic datasets (instead of
iterative reconstruction techniques) can provide accurate quantitative phase
information in the presence of high levels of noise.
PMID- 27607617
TI - Plasmonic coupled modes in metal-dielectric multilayer structures: Fano resonance
and giant field enhancement.
AB - We provide an overview of Fano resonance and plasmon induced transparency (PIT)
as well as on plasmons coupling in planar structures, and we discuss their
application in sensing and enhanced spectroscopy. Metal-insulator-metal (MIM)
structures, which are known to support symmetric and anti-symmetric surface
plasmon polaritons (SPPs) arising from the coupling between two SPPs at the metal
insulator interfaces, exhibit anticrossing behavior of the dispersion relations
arising from the coupling of the symmetric SPP and the metal/air SPP. Multilayer
structures, formed by a metal film and a high-index dielectric waveguide (WG),
separated by a low-index dielectric spacer layer, give narrow resonances of PIT
and Fano line shapes. An optimized Fano structure shows a giant field intensity
enhancement value of 106 in air at the surface of the high-index
dielectric WG. The calculated field enhancement factor and the figure of merit
for the sensitivity of the Fano structure in air can be 104 times as
large as those of the conventional surface plasmon resonance and WG sensors.
PMID- 27607618
TI - Atomically smooth hybrid crystalline-core glass-clad fibers for low-loss
broadband wave guiding.
AB - We demonstrate direct evidence for the first realization of atomically smooth
sapphire crystalline fiber cores with a surface variation of only ~1.9 A. The
hybrid glass-clad crystalline cores were grown by a laser-based fiber drawing
technique. Because of the improvement in crystal fiber quality, we were able, for
the first time, to comprehensively and quantitatively elucidate the correlation
between fiber nanostructure and optical loss. We also experimentally demonstrated
that high-temperature treatment has a significant impact on defect relaxation and
promotes excellent crystallinity, and hence enables low-loss optical wave
guiding. The experimentally measured propagation losses in the order of 0.01-0.1
dB/cm are the lowest ever reported among conventional Ti:sapphire channel
waveguides and ultrafast-laser-inscribed waveguides, and agree well with the
theory. Through experiments and numerical calculation, we have demonstrated that
low threshold and high efficiency of Ti:sapphire crystal fiber lasers are
possible with the atomic-level roughness, low-loss propagation, and high
crystallinity of the Ti:sapphire crystalline core.
PMID- 27607619
TI - High power and ultra-low-noise photodetector for squeezed-light enhanced
gravitational wave detectors.
AB - Current laser-interferometric gravitational wave detectors employ a self-homodyne
readout scheme where a comparatively large light power (5-50 mW) is detected per
photosensitive element. For best sensitivity to gravitational waves, signal
levels as low as the quantum shot noise have to be measured as accurately as
possible. The electronic noise of the detection circuit can produce a relevant
limit to this accuracy, in particular when squeezed states of light are used to
reduce the quantum noise. We present a new electronic circuit design reducing the
electronic noise of the photodetection circuit in the audio band. In the
application of this circuit at the gravitational-wave detector GEO 600 the shot
noise to electronic noise ratio was permanently improved by a factor of more than
4 above 1 kHz, while the dynamic range was improved by a factor of 7. The noise
equivalent photocurrent of the implemented photodetector and circuit is about
5MUA/Hz above 1 kHz with a maximum detectable photocurrent of 20 mA. With the new
circuit, the observed squeezing level in GEO 600 increased by 0.2 dB. The new
circuit also creates headroom for higher laser power and more squeezing to be
observed in the future in GEO 600 and is applicable to other optics experiments.
PMID- 27607620
TI - Terahertz 3D printed diffractive lens matrices for field-effect transistor
detector focal plane arrays.
AB - We present the concept, the fabrication processes and the experimental results
for materials and optics that can be used for terahertz field-effect transistor
detector focal plane arrays. More specifically, we propose 3D printed arrays of a
new type - diffractive multi-zone lenses of which the performance is superior to
that of previously used mono-zone diffractive or refractive elements and evaluate
them with GaN/AlGaN field-effect transistor terahertz detectors. Experiments
performed in the 300-GHz atmospheric window show that the lens arrays offer both
a good efficiency and good uniformity, and may improve the signal-to-noise ratio
of the terahertz field-effect transistor detectors by more than one order of
magnitude. In practice, we tested 3 * 12 lens linear arrays with printed circuit
board THz detector arrays used in postal security scanners and observed
significant signal-to-noise improvements. Our results clearly show that the
proposed technology provides a way to produce cost-effective, reproducible, flat
optics for large-size field-effect transistor THz-detector focal plane arrays.
PMID- 27607621
TI - Fast response Fabry-Perot interferometer microfluidic refractive index fiber
sensor based on concave-core photonic crystal fiber.
AB - We report a fast response microfluidic Fabry-Perot (FP) interferometer refractive
index (RI) fiber sensor based on a concave-core photonic crystal fiber (CPCF),
which is formed by directly splicing a section CPCF with a section of single mode
fiber. The CPCF is made by cleaving a section of multimode photonic crystal fiber
with an axial tension. The shallow concave-core of CPCF naturally forms the FP
cavity with a very short cavity length. The inherent large air holes in the
cladding of CPCF are used as the open channels to let liquid sample come in and
out of FP cavity. In order to shorten the liquid channel length and eliminate the
harmful reflection from the outside end face of the CPCF, the CPCF is cleaved
with a tilted tensile force. Due to the very small cavity capacity, the short
length and the large sectional area of the microfluidic channels, the proposed
sensor provides an easy-in and easy-out structure for liquids, leading to great
decrement of the measuring time. The proposed sensor exhibits fast measuring
speed, the measuring time is less than 359 and 23 ms for distilled water and pure
ethanol, respectively. We also experimentally study and demonstrate the superior
performances of the sensor in terms of high RI sensitivity, good linear response,
low temperature cross-sensitivity and easy fabrication.
PMID- 27607622
TI - Whispering gallery resonators with broken axial symmetry: Theory and experiment.
AB - Axial symmetry is the cornerstone for theory and applications of high-Q optical
whispering gallery resonators (WGRs). Nevertheless, research on birefringent
crystalline material persistently pushes towards breaking this symmetry. We show
theoretically and experimentally that the effect of broken axial symmetry, caused
by optical anisotropy, is modest for the resonant frequencies and Q-factors of
the WGR modes. Thus, the most important equatorial whispering gallery modes can
be quantitatively described and experimentally identified. At the same time, the
effect of broken axial symmetry on the light field distribution of the whispering
gallery modes is typically very strong. This qualitatively modifies the phase
matching for the chi(2) nonlinear processes and enables broad-band
second harmonic generation and optical parametric oscillation. The effect of weak
geometric ellipticity in nominally symmetric WGRs is also considered. Altogether
our findings pave the way for an extensive use of numerous birefringent (uniaxial
and biaxial) crystals with broad transparency window and large chi(2)
coefficients in nonlinear optics with WGRs.
PMID- 27607623
TI - Non-intrusive OSNR measurement of polarization-multiplexed signals with spectral
shaping and subject to fiber non-linearity with minimum channel spacing of
37.5GHz.
AB - A non-intrusive OSNR measurement technique relying on the detailed spectral
comparison of an optical signal with its "noise-free" spectrum is described,
including mathematical basis, validity conditions and algorithmic steps. The
technique's performance is experimentally demonstrated with 100G PM-QPSK and 200G
PM-16QAM signals subject to fiber non-linearity induced by 100G PM-QPSK and 10G
NRZ-OOK neighbors. The OSNR measurement performance is also demonstrated when
root-raised cosine spectral shaping is applied to the signals, with channel
spacings of 50GHz and 37.5GHz. Experimental results for OSNR levels up to 30dB
and launch powers up to 3dB above the optimum BER launch conditions are shown for
different system and signal configurations.
PMID- 27607624
TI - Reflection-mode Bessel-beam photoacoustic microscopy for in vivo imaging of
cerebral capillaries.
AB - A reflection-mode Bessel-beam photoacoustic microscope (BB-PAM) is developed for
the in vivo imaging of cerebral capillaries with extended depth of field (DoF).
The non-diffraction characteristic of Bessel beams means that a larger DoF can be
expected in the PAM compared to that using a Gaussian beam (GB). In our system,
we generate the Bessel beam using an axicon and an annular mask. The lateral
resolution of the system is estimated to be 1.6 MUm. The DoF is measured to be
483 MUm, and this is verified by imaging a carbon fiber network. The DoF of BB
PAM is about 7 times that of a GB-PAM. The cerebral vasculature of an open-skull
mouse is imaged using the developed BB-PAM to demonstrate its in vivo imaging
capability and advantages over GB-PAM.
PMID- 27607625
TI - Silver-film subwavelength gratings for polarizers in the terahertz and mid
infrared regions.
AB - Silver is proposed as a useful metal for thin metal-film subwavelength-grating
polarizers in both the terahertz and mid-infrared regions. A triangular Ag-film
grating for a terahertz-region polarizer fabricated on a resin substrate showed
measured TE-wave losses of higher than 45 dB in the frequency range of 0.5-2.2
THz, while TM-wave losses were lower than 0.75 dB in the range of 0.5-3THz. A
triangular double Ag-film grating structure on a thin silicon substrate with an
anti-reflection layer on its reverse side was fabricated for the polarizer in the
mid-infrared region. Measured TE-wave losses were higher than 27 dB in the
wavelength range of 16-21 MUm, while the minimum TM-wave loss was 3.5 dB at
around the wavelength of 19 MUm. Silver films are confirmed to be promising
candidates for fabricating high-performance polarizers in the terahertz and mid
infrared regions.
PMID- 27607626
TI - Tunable Fano resonances based on microring resonator with feedback coupled
waveguide.
AB - We experimentally demonstrate a tunable Fano resonance which originates from the
optical interference between two different resonant cavities using silicon micro
ring resonator with feedback coupled waveguide fabricated on silicon-on-insulator
(SOI) substrate. The resonance spectrum can be periodically tuned via changing
the resonant wavelengths of two resonators through the thermo-optic effect. In
addition to this, we can also change the transmission loss of the feedback
coupled waveguide (FCW) to tune the resonance spectrum by the injection free
carriers to FCW. We also build the theoretical model and we analyze the device
performance by using the scattering matrix method. The simulation results are in
a good agreement with the experimental results. The measurement maximum
extinction ratio of the Fano resonance is as high as 30.8dB. Therefore, the
proposed device is a most promising candidate for high on/off ratio optical
switching/modulating, high-sensitivity biochemical sensing.
PMID- 27607627
TI - Guided resonances on lithium niobate for extremely small electric field detection
investigated by accurate sensitivity analysis.
AB - We present a theoretical study of guided resonances (GR) on a thin film lithium
niobate rectangular lattice photonic crystal by band diagram calculations and 3D
Finite Difference Time Domain (FDTD) transmission investigations which cover a
broad range of parameters. A photonic crystal with an active zone as small as
13MUm*13MUm*0.7MUm can be easily designed to obtain a resonance Q value in the
order of 1000. These resonances are then employed in electric field (E-field)
sensing applications exploiting the electro optic (EO) effect of lithium niobate.
A local field factor that is calculated locally for each FDTD cell is proposed to
accurately estimate the sensitivity of GR based E-field sensor. The local field
factor allows well agreement between simulations and reported experimental data
therefore providing a valuable method in optimizing the GR structure to obtain
high sensitivities. When these resonances are associated with sub-picometer
optical spectrum analyzer and high field enhancement antenna design, an E-field
probe with a sensitivity of 50 MUV/m could be achieved. The results of our
simulations could be also exploited in other EO based applications such as EEG
(Electroencephalography) or ECG (Electrocardiography) probe and E-field frequency
detector with an 'invisible' probe to the field being detected etc.
PMID- 27607628
TI - Heterogeneous all-solid multicore fiber based multipath Michelson interferometer
for high temperature sensing.
AB - A compact high temperature sensor utilizing a multipath Michelson interferometer
(MI) structure based on weak coupling multicore fiber (MCF) is proposed and
experimentally demonstrated. The device is fabricated by program-controlled
tapering the spliced region between single mode fiber (SMF) and a segment of MCF.
After that, a spherical reflective structure is formed by arc-fusion splicing the
end face of MCF. Theoretical analysis has been implemented for this specific
multipath MI structure; beam propagation method based simulation and
corresponding experiments were performed to investigate the effect of taper and
spherical end face on system's performance. Benefiting from the multipath
interferences and heterogeneous structure between the center core and surrounding
cores of the all-solid MCF, an enhanced temperature sensitivity of 165 pm/
degrees C up to 900 degrees C and a high-quality interference spectrum with 25 dB
fringe visibility were achieved.
PMID- 27607629
TI - Color-tunable emission of quantum dots via strong exciton-plasmon coupling in
nanoporous gold structure at room temperature.
AB - We experimentally demonstrate the color-tunable emission of CdTe quantum dots
(QDs) enabled by strongly coupling the QDs to the nanoporous gold (NPG) structure
at room temperature. By manipulating the concentrations of the QDs or the
excitation flux of the laser, the coupling strength between the excitons in QDs
and the plasmons in NPG is controlled, resulting in a large Rabi splitting at the
magnitude of hundreds of meV and a photoluminescence (PL) tuning distinguishable
by the naked eye. In addition, such large PL tuning is enabled not only for the
strong coupling occurring on resonance but also off resonance. We believe that
our study offers a new approach towards designing and fabricating novel opto
electronic devices where dynamical and large spectral tuning of QD PL emission is
desired.
PMID- 27607630
TI - Comparison of models of fast saturable absorption in passively modelocked lasers.
AB - Fast saturable absorbers (FSAs) play a critical role in stabilizing many
passively modelocked lasers. The most commonly used averaged model to study these
lasers is the Haus modelocking equation (HME) that includes a third-order
nonlinear FSA. However, it predicts a narrow region of stability that is
inconsistent with experiments. To better replicate the laser physics, averaged
laser models that include FSAs with higher-than-third-order nonlinearities have
been introduced. Here, we compare three common FSA models to each other and to
the HME using the recently-developed boundary tracking algorithms. The three FSA
models are the cubic-quintic model, the sinusoidal model, and the algebraic
model. We find that all three models predict the existence of a stable high
energy solution that is not present in the HME and have a much larger stable
operating region. We also find that all three models predict qualitatively
similar stability diagrams. We conclude that averaged laser models that include
FSAs with higher-than-third-order nonlinearity should be used when studying the
stability of passively modelocked lasers.
PMID- 27607631
TI - Nonlinear ptychographic coherent diffractive imaging.
AB - Ptychographic Coherent diffractive imaging (PCDI) is a significant advance in
imaging allowing the measurement of the full electric field at a sample without
use of any imaging optics. So far it has been confined solely to imaging of
linear optical responses. In this paper we show that because of the coherence
preserving nature of nonlinear optical interactions, PCDI can be generalised to
nonlinear optical imaging. We demonstrate second harmonic generation PCDI,
directly revealing phase information about the nonlinear coefficients, and
showing the general applicability of PCDI to nonlinear interactions.
PMID- 27607632
TI - Real-time 3-D shape measurement with composite phase-shifting fringes and multi
view system.
AB - In recent years, fringe projection has become an established and essential method
for dynamic three-dimensional (3-D) shape measurement in different fields such as
online inspection and real-time quality control. Numerous high-speed 3-D shape
measurement methods have been developed by either employing high-speed hardware,
minimizing the number of pattern projection, or both. However, dynamic 3-D shape
measurement of arbitrarily-shaped objects with full sensor resolution without the
necessity of additional pattern projections is still a big challenge. In this
work, we introduce a high-speed 3-D shape measurement technique based on
composite phase-shifting fringes and a multi-view system. The geometry constraint
is adopted to search the corresponding points independently without additional
images. Meanwhile, by analysing the 3-D position and the main wrapped phase of
the corresponding point, pairs with an incorrect 3-D position or a considerable
phase difference are effectively rejected. All of the qualified corresponding
points are then corrected, and the unique one as well as the related period order
is selected through the embedded triangular wave. Finally, considering that some
points can only be captured by one of the cameras due to the occlusions, these
points may have different fringe orders in the two views, so a left-right
consistency check is employed to eliminate those erroneous period orders in this
case. Several experiments on both static and dynamic scenes are performed,
verifying that our method can achieve a speed of 120 frames per second (fps) with
25-period fringe patterns for fast, dense, and accurate 3-D measurement.
PMID- 27607633
TI - Minimizing inter-channel cross-phase modulation with optical phase conjugation in
asymmetric fibre links.
AB - Using analytic and numerical modelling of fibre transmission systems that employ
optical phase conjugation (OPC), we show inter-channel cross-phase modulation
depends on the integrated square error between nonlinear profiles before and
after OPC and that arranging amplifiers and tuning power levels is crucial to
minimizing noise. We derive modulation transparent formulas for phase noise and
optimal power settings. Examples are shown for 16 and 64 quadrature amplitude
modulation.
PMID- 27607634
TI - High-speed 405-nm superluminescent diode (SLD) with 807-MHz modulation bandwidth.
AB - III-nitride LEDs are fundamental components for visible-light communication
(VLC). However, the modulation bandwidth is inherently limited by the relatively
long carrier lifetime. In this letter, we present the 405 nm emitting
superluminescent diode (SLD) with tilted facet design on semipolar GaN substrate,
showing a broad emission of ~9 nm at 20 mW optical power. Owing to the fast
recombination (taue<0.35 ns) through the amplified spontaneous
emission, the SLD exhibits a significantly large 3-dB bandwidth of 807 MHz. A
data rate of 1.3 Gbps with a bit-error rate of 2.9 * 10-3 was obtained
using on-off keying modulation scheme, suggesting the SLD being a high-speed
transmitter for VLC applications.
PMID- 27607635
TI - An all fiber-optic multi-parameter structure health monitoring system.
AB - In this work, we present an all fiber-optics based multi-parameter structure
health monitoring system, which is able to monitor strain, temperature, crack and
thickness of metal structures. This system is composed of two optical fibers, one
for laser-acoustic excitation and the other for acoustic detection. A nano-second
1064 nm pulse laser was used for acoustic excitation and a 2 mm fiber Bragg
grating was used to detect the acoustic vibration. The feasibility of this system
was demonstrated on an aluminum test piece by the monitoring of the temperature,
strain and thickness changes, as well as the appearance of an artificial crack.
The multiplexing capability of this system was also preliminarily demonstrated.
PMID- 27607636
TI - Multiple rescattering processes in high-order harmonic generation from molecular
system.
AB - The molecular multiple rescattering processes have been theoretically
investigated via solving the time-dependent Schrodinger equation. Not only has
the physical model been established, but also the related rescatterings
originating from recombination with parent nucleus and with neighboring nucleus
have been distinguished. Moreover, it has shown that the rescatterings
originating from recombination with parent nucleus are similar with those atomic
rescatterings, while those rescatterings from recombination with neighboring
nucleus both before and after reversing the direction of the laser field are more
sensitive to the internuclear distance. With time-frequency distribution and
classical electron dynamics, the underlying mechanisms are revealed.
PMID- 27607637
TI - All-optical single-sideband frequency upconversion utilizing the XPM effect in an
SOA-MZI.
AB - An all-optical single sideband (OSSB) frequency upconverter based on the cross
phase modulation (XPM) effect is proposed and experimentally demonstrated to
overcome the power fading problem caused by the chromatic dispersion of fiber in
radio-over-fiber systems. The OSSB frequency upconverter consists of an arrayed
waveguide grating (AWG) and a semiconductor optical amplifier Mach-Zehnder
interferometer (SOA-MZI) and does not require an extra delay line used for phase
noise compensation. The generated OSSB radio frequency (RF) signal transmitted
over single-mode fibers up to 20 km shows a flat electrical RF power response as
a function of the fiber length. The upconverted electrical RF signal at 48 GHz
shows negligible degradation of the phase noise even without an extra delay line.
The measured phase noise of the upconverted RF signal (48 GHz) is -74.72 dBc/Hz
at an offset frequency of 10 kHz. The spurious free dynamic range (SFDR) measured
by a two-tone test to estimate the linearity of the OSSB frequency upconverter is
72.5 dB.Hz2/3.
PMID- 27607638
TI - All-optical NRZ wavelength conversion based on a single hybrid III-V/Si SOA and
optical filtering.
AB - We demonstrate all-optical wavelength conversion (AOWC) of non-return-to-zero
(NRZ) signal based on cross-gain modulation in a single heterogeneously
integrated III-V-on-silicon semiconductor optical amplifier (SOA) with an optical
bandpass filter. The SOA is 500 MUm long and consumes less than 250 mW electrical
power. We experimentally demonstrate 12.5 Gb/s and 40 Gb/s AOWC for both
wavelength up and down conversion.
PMID- 27607639
TI - Structured light field 3D imaging.
AB - In this paper, we propose a method by means of light field imaging under
structured illumination to deal with high dynamic range 3D imaging. Fringe
patterns are projected onto a scene and modulated by the scene depth then a
structured light field is detected using light field recording devices. The
structured light field contains information about ray direction and phase-encoded
depth, via which the scene depth can be estimated from different directions. The
multidirectional depth estimation can achieve high dynamic 3D imaging
effectively. We analyzed and derived the phase-depth mapping in the structured
light field and then proposed a flexible ray-based calibration approach to
determine the independent mapping coefficients for each ray. Experimental results
demonstrated the validity of the proposed method to perform high-quality 3D
imaging for highly and lowly reflective surfaces.
PMID- 27607640
TI - Structured surface reflector design for oblique incidence beam splitter at 610
GHz.
AB - An iterative alternate projection-based algorithm is developed to design
structured surface reflectors to operate as beam splitters at GHz and THz
frequencies. To validate the method, a surface profile is determined to achieve a
reflector at 610 GHz that generates four equal-intensity beams towards desired
directions of +/-12.6 degrees with respect to the specular reflection axis. A
prototype is fabricated and the beam splitter behavior is experimentally
demonstrated. Measurements confirm a good agreement (within 1%) with computer
simulations using Feko, validating the method. The beam splitter at 610 GHz has a
measured efficiency of 78% under oblique incidence illumination that ensures a
similar intensity between the four reflected beams (variation of about 1%).
PMID- 27607641
TI - Fabrication of axicon microlenses on capillaries and microstructured fibers by
wet etching.
AB - A facile method is presented for the fabrication of microlenses at the facet of
fused silica capillaries and microstructured fibers. After submersion in hydrogen
fluoride solution water is pumped slowly through the center hole of the capillary
microchannel to create an etchant gradient extending from the capillary axis. The
desired axicon angle is generated by adjusting the etching time and/or
concentration of the etchant. Similarly, flow- assisted HF etching of a custom
microstructured fiber containing nine microchannels produces nine individual
microlenses simultaneously at the fiber facet, where each microaxicon lens shows
a similar focusing pattern. A theoretical model of the flow-assisted etching
process is used to determine the axicon angle and post angle. Also, a simple ray
based model was applied to characterize the focusing properties of the
microaxicons in good agreement with experimental observations.
PMID- 27607642
TI - Amplification of noise-like pulses generated from a graphene-based Tm-doped all
fiber laser.
AB - We report on the generation of noise-like pulse (NLP) trains in a Tm-doped fiber
laser mode-locked by multilayer graphene saturable absorber. The spectral
bandwidth obtained directly from the oscillator exceeds 60 nm, centered at 1950
nm, with 23.5 MHz repetition rate. The pulses were also amplified in a fully
fiberized amplifier based on a double-cladding Tm-doped fiber. The system was
capable of delivering 1.21 W of average power, which corresponds to 51.5 nJ
energy stored in the noise-like bundle. We believe that the presented source
might serve as a pump for supercontinuum generation in highly nonlinear fibers.
PMID- 27607643
TI - Tunable Bragg filters with a phase transition material defect layer.
AB - We propose an all-solid-state tunable Bragg filter with a phase transition
material as the defect layer. Bragg filters based on a vanadium dioxide defect
layer sandwiched between silicon dioxide/titanium dioxide Bragg gratings are
experimentally demonstrated. Temperature dependent reflection spectroscopy shows
the dynamic tunability and hysteresis properties of the Bragg filter. Temperature
dependent Raman spectroscopy reveals the connection between the tunability and
the phase transition of the vanadium dioxide defect layer. This work paves a new
avenue in tunable Bragg filter designs and promises more applications by
combining phase transition materials and optical cavities.
PMID- 27607644
TI - Role of material loss and mode volume of plasmonic nanocavities for strong
plasmon-exciton interactions.
AB - We investigate the role of material loss and mode volume of plasmonic
nanostructures on strong plasmon-exciton coupling. We find that the field
enhancement, and therefore loss, is not important for the magnitude of the Rabi
splitting as such, but instead it is determined by the mode volume. Nevertheless,
for reaching true strong coupling condition, that is, coupling greater than any
dissipation, it is important to compromise losses. We also show that using such
popular geometries as a dimer of two spheres or bow-tie nanoantennas, does not
allow compressing the mode volume much in comparison to a single nanoparticle
case, except for very narrow gaps, but rather it allows for efficient extraction
of the mode out of the metal thus making it more accessible for excitons to
interact with. Even more efficient mode extraction is achieved when high
refractive index dielectric is placed in the gap. Our findings may find practical
use for quantum plasmonics applications.
PMID- 27607645
TI - Time-domain Raman analytical forward solvers.
AB - A set of time-domain analytical forward solvers for Raman signals detected from
homogeneous diffusive media is presented. The time-domain solvers have been
developed for two geometries: the parallelepiped and the finite cylinder. The
potential presence of a background fluorescence emission, contaminating the Raman
signal, has also been taken into account. All the solvers have been obtained as
solutions of the time dependent diffusion equation. The validation of the solvers
has been performed by means of comparisons with the results of "gold standard"
Monte Carlo simulations. These forward solvers provide an accurate tool to
explore the information content encoded in the time-resolved Raman measurements.
PMID- 27607646
TI - High bandwidth on-chip capacitive tuning of microtoroid resonators.
AB - We report on the design, fabrication and characterization of silica microtoroid
based cavity opto-electromechanical systems (COEMS). Electrodes patterned onto
the microtoroid resonators allow for rapid capacitive tuning of the optical
whispering gallery mode resonances while maintaining their ultrahigh quality
factor, enabling applications such as efficient radio to optical frequency
conversion, optical routing and switching applications.
PMID- 27607647
TI - Influence of non-Kolmogorov atmospheric turbulence on the beam quality of vortex
beams.
AB - Based on the extended Huygens-Fresnel principle and the definition of second
order moments of the Wigner distribution function (WDF), the analytical
expressions for the propagation factors (M2-factors) and Strehl ratio
SR of the Gaussian Schell-model (GSM) vortex beams and GSM non-vortex
beams propagation through non-Kolmogorov atmospheric turbulence are derived, and
used to study the influence of non-Kolmogorov atmospheric turbulence on beam
quality of the GSM vortex beams. It is shown that the smaller the generalized
structure constant and the outer scale of turbulence are, and the bigger the
inner scale of turbulence is, the smaller the normalized propagation factor is,
the bigger the Strehl ratio is, and the better the beam quality of GSM vortex
beams in atmospheric turbulence is. The variation of beam quality with the
generalized exponent alpha is nonmonotonic, when alpha = 3.11, the beam quality
of the GSM vortex beams is the poorest through non-Kolmogorov atmospheric
turbulence. GSM vortex beams is less affected by turbulence than GSM non-vortex
beams under certain condition, and will be useful in long-distance free-space
optical communications.
PMID- 27607648
TI - Estimating the surface layer refractive index structure constant over snow and
sea ice using Monin-Obukhov similarity theory with a mesoscale atmospheric model.
AB - Since systematic direct measurements of refractive index structure constant (
Cn2) for many climates and seasons are not available, an indirect approach is
developed in which Cn2 is estimated from the mesoscale atmospheric model outputs.
In previous work, we have presented an approach that a state-of-the-art mesoscale
atmospheric model called Weather Research and Forecasting (WRF) model coupled
with Monin-Obukhov Similarity (MOS) theory which can be used to estimate surface
layer Cn2 over the ocean. Here this paper is focused on surface layer Cn2 over
snow and sea ice, which is the extending of estimating surface layer Cn2
utilizing WRF model for ground-based optical application requirements. This
powerful approach is validated against the corresponding 9-day Cn2 data from a
field campaign of the 30th Chinese National Antarctic Research Expedition
(CHINARE). We employ several statistical operators to assess how this approach
performs. Besides, we present an independent analysis of this approach
performance using the contingency tables. Such a method permits us to provide
supplementary key information with respect to statistical operators. These
methods make our analysis more robust and permit us to confirm the excellent
performances of this approach. The reasonably good agreement in trend and
magnitude is found between estimated values and measurements overall, and the
estimated Cn2 values are even better than the ones obtained by this approach over
the ocean surface layer. The encouraging performance of this approach has a
concrete practical implementation of ground-based optical applications over snow
and sea ice.
PMID- 27607649
TI - NIR- and SWIR-based on-orbit vicarious calibrations for satellite ocean color
sensors.
AB - The near-infrared (NIR) and shortwave infrared (SWIR)-based atmospheric
correction algorithms are used in satellite ocean color data processing, with the
SWIR-based algorithm particularly useful for turbid coastal and inland waters. In
this study, we describe the NIR- and two SWIR-based on-orbit vicarious
calibration approaches for satellite ocean color sensors, and compare results
from these three on-orbit vicarious calibrations using satellite measurements
from the Visible Infrared Imaging Radiometer Suite (VIIRS) onboard the Suomi
National Polar-orbiting Partnership (SNPP). Vicarious calibration gains for VIIRS
spectral bands are derived using the in situ normalized water-leaving radiance
nLw(lambda) spectra from the Marine Optical Buoy (MOBY) in waters off Hawaii. The
SWIR vicarious gains are determined using VIIRS measurements from the South
Pacific Gyre region, where waters are the clearest and generally stable.
Specifically, vicarious gain sets for VIIRS spectral bands of 410, 443, 486, 551,
and 671 nm derived from the NIR method using the NIR 745 and 862 nm bands, the
SWIR method using the SWIR 1238 and 1601 nm bands, and the SWIR method using the
SWIR 1238 and 2257 nm bands are (0.979954, 0.974892, 0.974685, 0.965832,
0.979042), (0.980344, 0.975344, 0.975357, 0.965531, 0.979518), and (0.980820,
0.975609, 0.975761, 0.965888, 0.978576), respectively. Thus, the NIR-based
vicarious calibration gains are consistent with those from the two SWIR-based
approaches with discrepancies mostly within ~0.05% from three data processing
methods. In addition, the NIR vicarious gains (745 and 862 nm) derived from the
two SWIR methods are (0.982065, 1.00001) and (0.981811, 1.00000), respectively,
with the difference ~0.03% at the NIR 745 nm band. This is the fundamental basis
for the NIR-SWIR combined atmospheric correction algorithm, which has been used
to derive improved satellite ocean color products over open oceans and turbid
coastal/inland waters. Therefore, a unified vicarious gain set for VIIRS bands M1
M8 and M10-M11 has been implemented in the VIIRS ocean color data processing.
Using the unified vicarious gain set, VIIRS mission-long ocean color data have
been successfully reprocessed using the NIR-, SWIR-, and NIR-SWIR-based
atmospheric correction algorithms.
PMID- 27607650
TI - Metamaterial perfect absorber based on artificial dielectric "atoms".
AB - In this work, we numerically designed and then experimentally verified a
metamaterial perfect absorber based on artificial dielectric "atoms". This
metamaterial absorber is composed of dielectric ceramic material
(SrTiO3) "atoms" embedded in a background matrix on a metal plate. The
dielectric "atoms" couple strongly to the incident electric and magnetic fields
at the Mie resonance mode, leading to the narrow perfect absorption band with
simulated and experimental absorptivities of 99% and 98.5% at 8.96 GHz,
respectively. The designed metamaterial perfect absorber is polarization
insensitive and can operate in wide angle incidence.
PMID- 27607651
TI - Plasmon modes of circular cylindrical double-layer graphene.
AB - In this paper, a theoretical investigation on plasmon modes in a circular
cylindrical double-layer graphene structure is presented. Due to the interlayer
electromagnetic interaction, there exist two branches of plasmon modes, the
optical plasmon mode and the acoustic plasmon mode. The characteristics of these
two modes, such as mode pattern, effective mode index and propagation loss, are
analyzed. The modal behaviors can be effectively tuned by changing the distance
between two graphene layers, the chemical potential of graphene and the
permittivity of interlayer dielectric. Importantly, the breakup of tradeoff
between mode confinement and propagation loss is discovered in the distance
dependent modal behavior, which originates from the unique dispersion properties
of a double-layer graphene system. As a consequence, both strong mode confinement
and longer propagation length can be achieved. Our results may provide good
opportunities for developing applications based on graphene plasmonics in
circular cylindrical structure.
PMID- 27607652
TI - All-metal structural color printing based on aluminum plasmonic metasurfaces.
AB - An all-metal structural color printing platform based on aluminum plasmonic
metasurfaces is proposed and demonstrated with high color performance using only
a one-step etching process on aluminum surface. A wide visible color range is
realized with the designed metallic square-shaped disk arrays by simply adjusting
the geometrical parameters of the disk etching depth, disk width and unit cell
period. The demonstrated all-metal microscale structural color printing on
aluminum surface offers great potential for many practical color related
applications.
PMID- 27607653
TI - Practical continuous-variable quantum key distribution without finite sampling
bandwidth effects.
AB - In a practical continuous-variable quantum key distribution system, finite
sampling bandwidth of the employed analog-to-digital converter at the receiver's
side may lead to inaccurate results of pulse peak sampling. Then, errors in the
parameters estimation resulted. Subsequently, the system performance decreases
and security loopholes are exposed to eavesdroppers. In this paper, we propose a
novel data acquisition scheme which consists of two parts, i.e., a dynamic delay
adjusting module and a statistical power feedback-control algorithm. The proposed
scheme may improve dramatically the data acquisition precision of pulse peak
sampling and remove the finite sampling bandwidth effects. Moreover, the optimal
peak sampling position of a pulse signal can be dynamically calibrated through
monitoring the change of the statistical power of the sampled data in the
proposed scheme. This helps to resist against some practical attacks, such as the
well-known local oscillator calibration attack.
PMID- 27607654
TI - Picosecond laser-induced water condensation in a cloud chamber.
AB - We investigated water condensation in a laboratory cloud chamber induced by
picosecond (ps) laser pulses at ~350 ps (800 nm/1-1000 Hz) with a maximum peak
power of ~25 MW. The peak power was much lower than the critical power for self
focusing in air (~3-10 GW depending on the pulse duration). Sparks, airflow and
snow formation were observed under different laser energies or repetition rates.
It was found that weaker ps laser pulses can also induce water condensation by
exploding and breaking down ice crystals and/or water droplets into tiny
particles although there was no formation of laser filament. These tiny particles
would grow until precipitation in a super-saturation zone due to laser-induced
airflow in a cold region with a large temperature gradient.
PMID- 27607655
TI - Self-recovery effect of orbital angular momentum mode of circular beam in weak
non-Kolmogorov turbulence.
AB - It is generally true that the orbital angular momentum (OAM) mode persistently
degenerate when a vortex beam propagates in the atmospheric turbulence. Here,
however, we unveil an interesting self-recovery effect of OAM mode of the
circular beam (CiB) in weak non-Kolmogorov turbulence. We show that the CiB
displays the self-focusing effect and has clear focus in the weak non-Kolmogorov
turbulence if we choose proper complex parameters, and the detection probability
of the original OAM mode reaches the maximum at the focus. Our study proposes a
method to alleviate the turbulent effects on OAM-based communication.
PMID- 27607656
TI - Analytic model for the complex effective index dispersion of metamaterial
cladding large-area hollow core fibers.
AB - We present a mathematical model that allows interpreting the dispersion and
attenuation of modes in hollow-core fibers (HCFs) on the basis of single
interface reflection, giving rise to analytic and semi-analytic expressions for
the complex effective indices in the case where the core diameter is large and
the guiding is based on the reflection by a thin layer. Our model includes two
core-size independent reflection parameters and shows the universal inverse-cubed
core diameter dependence of the modal attenuation of HCFs. It substantially
reduces simulation complexity and enables large scale parameter sweeps, which we
demonstrate on the example of a HCF with a highly anisotropic metallic nanowire
cladding, resembling an indefinite metamaterial at high metal filling fractions.
We reveal design rules that allow engineering modal discrimination and show that
metamaterial HCFs can principally have low losses at mid-IR wavelengths (< 1 dB/m
at 10.6 um). Our model can be applied to a great variety of HCFs with large core
diameters and can be used for advanced HCF design and performance optimization,
in particular with regard to dispersion engineering and modal discrimination.
PMID- 27607657
TI - Reconfigurable symmetric pulses generation using on-chip cascaded optical
differentiators.
AB - We report a type of programmable pulse shaping method based on cascaded frequency
detuned optical differentiators. By properly adjusting the central wavelength of
each differentiator, a large variety of symmetric pulses can be generated from a
transform-limited Gaussian-like pulse. We numerically and experimentally
demonstrate the generation of flat-top, parabolic and triangular pulses with
tunable pulse widths from a 20-ps Gaussian-like pulse, using no more than three
cascaded differentiators. It can be found that as more differentiators are used,
higher synthesized accuracy and larger tuning range of pulse widths can be
obtained in general. Additionally, in our experiment, we design and fabricate
thermally tunable delay interferometers on the silicon-on-insulator (SOI)
platform to work as optical differentiators, which can help us realize the
shaping system with small footprint (943MUm * 395MUm) and high stability.
PMID- 27607658
TI - Ultra-compact, broadband tunable optical bandstop filters based on a multimode
one-dimensional photonic crystal waveguide.
AB - In this paper, ultra-compact, broadband tunable optical bandstop filters (OBSFs)
based on a multimode one-dimensional photonic crystal waveguide (PhCW) are
proposed and systematically investigated. For the wavelengths in the mini
stopband, the input mode is coupled to a contra-propagating higher order mode by
the PhCW and then radiates in a taper, resulting in a stopband at the output with
low backreflection at the input. Three-dimensional finite-difference time-domain
method is employed to study the OBSFs. The influence of main structural
parameters is analyzed, and the design is optimized to reduce the back-reflection
and band sidelobes. Using localized heating, we can shift the stopband and tune
the bandwidth continuously by cascading the proposed structures. Due to the
strong grating strength, our device provides a more compact footprint (40 MUm * 1
MUm) and much broader stopband (bandwidth of up to 84 nm), compared to the
counterparts based on microrings, long-period waveguide gratings, and multimode
two-dimensional PhCWs.
PMID- 27607659
TI - Model for a pulsed terahertz quantum cascade laser under optical feedback.
AB - Optical feedback effects in lasers may be useful or problematic, depending on the
type of application. When semiconductor lasers are operated using pulsed-mode
excitation, their behavior under optical feedback depends on the electronic and
thermal characteristics of the laser, as well as the nature of the external
cavity. Predicting the behavior of a laser under both optical feedback and pulsed
operation therefore requires a detailed model that includes laser-specific
thermal and electronic characteristics. In this paper we introduce such a model
for an exemplar bound-to-continuum terahertz frequency quantum cascade laser
(QCL), illustrating its use in a selection of pulsed operation scenarios. Our
results demonstrate significant interplay between electro-optical, thermal, and
feedback phenomena, and that this interplay is key to understanding QCL behavior
in pulsed applications. Further, our results suggest that for many types of QCL
in interferometric applications, thermal modulation via low duty cycle pulsed
operation would be an alternative to commonly used adiabatic modulation.
PMID- 27607660
TI - Efficient laser operation based on transparent Nd:Lu2O3
ceramic fabricated by Spark Plasma Sintering.
AB - Efficient laser operation of Nd:Lu2O3 ceramic fabricated by
Spark Plasma Sintering (SPS) was demonstrated. Transparent
Nd:Lu2O3 ceramic was successfully fabricated by Spark
Plasma Sintering and its laser experiment was done. On the
4F3/2 to 4I11/2 transition, the
obtained maximum output is 1.25W at the absorbed pump power of 4.15W with a slope
efficiency of 38% and two spectral lines at 1076.7nm and 1080.8nm oscillated
simultaneously. The slope efficiency of 38% is near two times higher than the
previously demonstrated SPSed Nd:Lu2O3 ceramic lasers. On
the 4F3/2 to 4I13/2 transition, the
laser operated at the wavelength of 1359.7nm and the maximum output of 200mW was
obtained at the absorbed pump power of 2.7W.
PMID- 27607661
TI - Partially hollowed ultra-thin dielectric meta-surface for transmission
manipulation.
AB - Impressive optical properties are numerically demonstrated in the partially
hollowed dielectric meta-surface (p-HDMS), which consists of an air cavity array
intercalated in an ultra-thin (~lambda/6) high-index dielectric film.
Multispectral transmission band-stop response with near-perfect spectral
modulation depth is achieved. The spectral slop is up to 80%/nm, indicating the
sharp and narrowband transmission behavior. Classical Malus law is confirmed by
this sub-wavelength platform. Moreover, the multispectral light propagation
manipulation can be perfectly reproduced by using the actual dielectric with
absorption loss. In this all-dielectric meta-surface, conduction loss is avoided
compared to its metallic plasmonic counterpart. Such configurations can therefore
serve as excellent alternatives for plasmonic meta-surfaces and constitute an
important step in nanophotonics.
PMID- 27607662
TI - Ultra-broadband infrared metasurface absorber.
AB - By using sub-wavelength resonators, metamaterial absorber shows great potential
in many scientific and technical applications due to its perfect absorption
characteristics. For most practical applications, the absorption bandwidth is one
of the most important performance metrics. In this paper, we demonstrate the
design of an ultra-broadband infrared absorber based on metasurface. Compared
with the prior work [Opt. Express22(S7), A1713-A1724 (2014)], the proposed
absorber shows more than twice the absorption bandwidth. The simulated total
absorption exceeds 90% from 7.8 to 12.1 um and the full width at half maximum is
50% (from 7.5 to 12.5 MUm), which is achieved by using a single layer of
metasurface. Further study demonstrates that the absorption bandwidth can be
greatly expanded by using two layers of metasurface, i.e. dual-layered absorber.
The total absorption of the dual-layered absorber exceeds 80% from 5.2 to 13.7 um
and the full width at half maximum is 95% (from 5.1 to 14.1 MUm), much greater
than those previously reported for infrared spectrum. The absorption decreases
with fluctuations as the incident angle increases but remains quasi-constant up
to relatively large angles.
PMID- 27607663
TI - Grating-flanked plasmonic coaxial apertures for efficient fiber optical tweezers.
AB - Subwavelength plasmonic apertures have been foundational for direct optical
manipulation of nanoscale specimens including sub-100 nm polymeric beads,
metallic nanoparticles and proteins. While most plasmonic traps result in two
dimensional localization, three-dimensional manipulation has been demonstrated by
integrating a plasmonic aperture on an optical fiber tip. However, such 3D traps
are usually inefficient since the optical mode of the fiber and the subwavelength
aperture only weakly couple. In this paper we design more efficient optical-fiber
based plasmonic tweezers combining a coaxial plasmonic aperture with a plasmonic
grating coupler at the fiber tip facet. Using full-field finite difference time
domain analysis, we optimize the grating design for both gold and silver fiber
based coaxial tweezers such that the optical transmission through the apertures
is maximized. With the optimized grating, we show that the maximum transmission
efficiency increases from 2.5% to 19.6% and from 1.48% to 16.7% for the gold and
silver structures respectively. To evaluate their performance as optical
tweezers, we calculate the optical forces and the corresponding trapping
potential on dielectric particles interacting with the apertures. We demonstrate
that the enahncement in the transmission translates into an equivalent increase
in the optical forces. Consequently, the optical power required to achieve stable
optical trapping is significantly reduced allowing for efficient localization and
3D manipulation of sub-30 nm dielectric particles.
PMID- 27607664
TI - Spinning and orbiting motion of particles in vortex beams with circular or radial
polarizations.
AB - Focusing fields of optical vortex (OV) beams with circular or radial
polarizations carry both spin angular momentum (SAM) and orbital angular momentum
(OAM), and can realize non-axial spinning and orbiting motion of absorptive
particles. Using the T-matrix method, we evaluate the optical forces and torques
exerted on micro-sized particles induced by the OV beams. Numerical results
demonstrate that the particle is trapped on the circle of intensity maxima, and
experiences a transverse spin torque along azimuthal direction, a longitudinal
spin torque, and an orbital torque, respectively. The direction of spinning
motion is not only related to the sign of topological charge of the OV beam, but
also to the polarization state. However, the topological charge controls the
direction of orbiting motion individually. Optically induced rotations of
particles with varying sizes and absorptivity are investigated in OV beams with
different topological charges and polarization states. These results may be
exploited in practical optical manipulation, especially for optically induced
rotations of micro-particles.
PMID- 27607665
TI - Optimization of the particle density to maximize the SERS enhancement factor of
periodic plasmonic nanostructure array.
AB - Low-cost surface-enhanced Raman scattering (SERS) substrate with the largest
possible enhancement factor is highly desirable for SERS-based sensing
applications. In this work, we systematically investigated how the density of
plasmonic nanostructures affects the intensity of SERS signal. By directly
depositing of metallic layer on electron-beam-lithography defined dielectric
nanoposts, plasmonic structures array with different densities were reliably
fabricated for SERS measurements. Two main experimental phenomena were obtained:
(1) the SERS intensity did not increase monotonically when increasing the density
of plasmonic structures, and (2) these ultra-dense plasmonic structures resulted
in the maximal SERS intensity. These results could be well explained based on
finite-difference time domain (FDTD) simulations and provide robust experimental
evidences to guide the design of the best possible SERS substrate.
PMID- 27607666
TI - How an oxide shell affects the ultraviolet plasmonic behavior of Ga, Mg, and Al
nanostructures.
AB - The ultraviolet (UV) range presents new challenges for plasmonics, with
interesting applications ranging from engineering to biology. In previous
research, gallium, aluminum, and magnesium were found to be very promising UV
plasmonic metals. However, a native oxide shell surrounds nanostructures of these
metals that affects their plasmonic response. Here, through a nanoparticle-oxide
core-shell model, we present a detailed electromagnetic analysis of how oxidation
alters the UV-plasmonic response of spherical or hemisphere-on-substrate
nanostructures made of those metals by analyzing the spectral evolution of two
parameters: the absorption efficiency (far-field analysis) and the enhancement of
the local intensity averaged over the nanoparticle surface (near-field analysis).
PMID- 27607667
TI - Third-order linearization for self-beating filtered microwave photonic systems
using a dual parallel Mach-Zehnder modulator.
AB - We develop, analyze and apply a linearization technique based on dual parallel
Mach-Zehnder modulator to self-beating microwave photonics systems. The approach
enables broadband low-distortion transmission and reception at expense of a
moderate electrical power penalty yielding a small optical power penalty (<1 dB).
PMID- 27607668
TI - Dispersion-engineered multicore fibers for distributed radiofrequency signal
processing.
AB - We report a trench-assisted heterogeneous multicore fiber optimized in terms of
higher-order dispersion and crosstalk for radiofrequency true time delay
operation. The analysis of the influence of the core refractive index profile on
the dispersion slope and effective index reveals a tradeoff between the behavior
of the crosstalk against fiber curvatures and the linearity of the propagation
group delay. We investigate the optimization of the multicore fiber in the
framework of this tradeoff and present a design that features a group delay
relative error below 5% for an optical wavelength range up to 100 nm and a
crosstalk level below -80 dB for bending radii larger than 103 mm. The
performance of the true time delay line is validated in the context of microwave
signal filtering and optical beamforming for phased array antennas. This work
opens the way towards the development of compact fiber-integrated solutions that
enable the implementation of a variety of distributed signal processing
functionalities that will be key in future fiber-wireless communications networks
and systems.
PMID- 27607669
TI - Highly sensitive temperature sensor based on cascaded polymer-microbubble
cavities by employing a subtraction between reciprocal thermal responses.
AB - A miniature, robust, and highly sensitive optical fiber temperature sensor based
on cascaded polymer-microbubble cavities was fabricated by polymer-filling and
subsequent heat-curing process. The expansion of polymer cavity results in the
compression of microbubble cavity when the sensor is heated. We demodulated the
interference spectrum by means of the fast-Fourier transform (FFT) and signal
filtering. Since the thermal response of the polymer cavity is positive and that
of the microbubble cavity is negative, a high sensitivity of the temperature
sensor is achieved by a subtraction between the two reciprocal thermal responses.
Experimental results show that the sensitivity of the temperature sensor is as
high as 5.013 nm/ degrees C in the measurement range between 20 degrees C and 55
degrees C. Meanwhile, such a sensor has potential for mass production, owing to
the simple, nontoxic, and cost-effective process of fabrication.
PMID- 27607670
TI - Broadband terahertz absorption enabled by coating an ultrathin antireflection
film on doped semiconductor.
AB - We show that perfect absorption of terahertz wave can be achieved in a compact
system where an ultrathin film of lossless dielectric is coated on a doped
semiconductor substrate. Due to the nontrivial reflection phase shift at the
interface between the two media, strong resonant behavior and the concomitant
antireflection occur at wavelengths that are much larger than the thickness of
the dielectric film, resulting in strong absorption of the incident wave in a
wide frequency range. Using this mechanism, we design a broadband terahertz
absorber by coating a Ge film on a highly doped GaAs substrate. We show that such
a system not only has a perfect absorption peak, but also exhibits high
absorptance (over 0.9) within a fractional bandwidth of over 20%. By varying the
free carrier density in the GaAs substrate, the central frequency of the
absorption band can be tuned from 1.79 to 2.69 THz. In addition, the absorption
performance of the proposed system is shown to be insensitive to both incident
angle and polarization. Our results offer a low-cost way for the design of
absorption-based THz devices.
PMID- 27607671
TI - Phase sensitive properties and coherent manipulation of a photonic crystal
microcavity.
AB - We present phase sensitive cavity field measurements on photonic crystal
microcavities. The experiments have been performed as autocorrelation
measurements with ps double pulse laser excitation for resonant and detuned
conditions. Measured E-field autocorrelation functions reveal a very strong
detuning dependence of the phase shift between laser and cavity field and of the
autocorrelation amplitude of the cavity field. The fully resolved phase
information allows for a precise frequency discrimination and hence for a precise
measurement of the detuning between laser and cavity. The behavior of the
autocorrelation amplitude and phase and their detuning dependence can be fully
described by an analytic model. Furthermore, coherent control of the cavity field
is demonstrated by tailored laser excitation with phase and amplitude controlled
pulses. The experimental proof and verification of the above described phenomena
became possible by an electric detection scheme, which employs planar photonic
crystal microcavity photo diodes with metallic Schottky contacts in the defect
region of the resonator. The applied photo current detection was shown to work
also efficiently at room temperature, which make electrically contacted
microcavities attractive for real world applications.
PMID- 27607672
TI - Nonlinear optical responses in two-dimensional transition metal dichalcogenide
multilayer: WS2, WSe2, MoS2 and Mo
0.5 W0.5 S2.
AB - Synthetic two-dimensional transition metal dichalcogenides such as, tungsten
disulphide (WS2), tungsten diselenide (WSe2), molybdenum
disulphide (MoS2) as well as mixed molybdenum tungsten disulphide
(Mo0.5W0.5S2) single crystals were grown by the
chemical vapor transport method using halogens (bromine or chlorine) as transport
agents. Multi- layer samples were cleaved from the single crystals, and their
nonlinear optical (NLO) properties were obtained from both open aperture and
closed aperture Z-scan measurements using a picosecond mode-locked Nd: YAG laser
operating at a wavelength of 1064 nm, with pulse duration of 25 ps, and 20 Hz
repetition rate. Both WS2 and MoS2 exhibited nonlinear
saturable absorption (SA), whereas WSe2 and
Mo0.5W0.5S2 showed nonlinear two-photon
absorption (2PA). A large 2PA coefficient beta as high as + 1.91x10-8
cm/W was obtained for the Mo0.5W0.5S2, and an
index of refraction coefficient gamma = -2.47x10-9 cm2/W
was obtained for the WSe2 sample.
PMID- 27607673
TI - Localized surface plasmon for enhanced lasing performance in solution-processed
perovskites.
AB - A promising method to promote the lasing performance of solution-processed
organic-inorganic lead-halide perovskites has been demonstrated. With the adding
Ag and PMMA thin films, the threshold excitation power for low-temperature lasing
action in perovskites can be greatly reduced by over two orders of magnitude than
that acquired in bare perovskite layers, ascribing to the strong exciton-plasmon
coupling between the Ag and perovskite films. Also, the PMMA layer can be
exploited to prevent the perovskite degradation from the hydrolysis in ambient
environment, achieving long-lasting light-emitting performance. The advantages
exhibited by the hybrid perovskite configuration would be very promising in
making practical laser devices.
PMID- 27607674
TI - Characterizing the phytoplankton soup: pump and plumbing effects on the particle
assemblage in underway optical seawater systems.
AB - Many optical and biogeochemical data sets, crucial for algorithm development and
satellite data validation, are collected using underway seawater systems over the
course of research cruises. Phytoplankton and particle size distribution (PSD) in
the ocean is a key measurement, required in oceanographic research and ocean
optics. Using a data set collected in the North Atlantic, spanning different
oceanic water types, we outline the differences observed in concurrent samples
collected from two different flow-through systems: a permanently plumbed science
seawater supply with an impeller pump, and an independent system with shorter,
clean tubing runs and a diaphragm pump. We observed an average of 40% decrease in
phytoplankton counts, and significant changes to the PSD in 10-45 um range, when
comparing impeller and diaphragm pump systems. Change in PSD seems to be more
dependent on the type of the phytoplankton, than the size, with photosynthetic
ciliates displaying the largest decreases in cell counts (78%). Comparison of
chlorophyll concentrations across the two systems demonstrated lower sensitivity
to sampling system type. Observed changes in several measured biogeochemical
parameters (associated with phytoplankton size distribution) using the two
sampling systems, should be used as a guide towards building best practices when
it comes to the deployment of flow-through systems in the field for examining
optics and biogeochemistry. Using optical models, we evaluated potential impact
of the observed change in measured phytoplankton size spectra onto scattering
measurements, resulting in significant differences between modeled optical
properties across systems (~40%). Researchers should be aware of the methods used
with previously collected data sets, and take into consideration the potentially
significant and highly variable ecosystem-dependent biases in designing field
studies in the future.
PMID- 27607675
TI - Spatiotemporal modulation instability as off-axis parametric amplification:
insights from the phase.
AB - The canonical linear-stability analysis of spatiotemporal modulation instability
(MI), which treats MIs as instabilities of the steady-state solution of the field
evolution equation with respect to weak complex harmonic perturbations, is shown
to be physically equivalent to a coupled-wave analysis of off-axis parametric
amplification of the Stokes and anti-Stokes fields by an intense pump wave. With
an appropriate space-evolution transfer matrix, a complex harmonic trial function
used in the standard MI model translates into a pair of coupled off-axis waves,
of which one is exponentially growing, while the other is exponentially
decreasing, thus recovering a two-wave field structure that is inherent in the
fields undergoing parametric amplification through four-wave mixing. Analysis of
the phase of these fields offers useful physical insights into high-order
dispersion effects in spatiotemporal MIs, suggests a physically transparent and
accurate method to include high-order dispersion in MI gain calculations, and
reveals new spatiotemporal MI effects induced by high-order dispersion.
PMID- 27607676
TI - Adaptive step-size strategy for noise-robust Fourier ptychographic microscopy.
AB - The incremental gradient approaches, such as PIE and ePIE, are widely used in the
field of ptychographic imaging due to their great flexibility and computational
efficiency. Nevertheless, their stability and reconstruction quality may be
significantly degraded when non-negligible noise is present in the image. Though
this problem is often attributed to the non-convex nature of phase retrieval, we
found the reason for this is more closely related to the choice of the step-size,
which needs to be gradually diminishing for convergence even in the convex case.
To this end, we introduce an adaptive step-size strategy that decreases the step
size whenever sufficient progress is not made. The synthetic and real experiments
on Fourier ptychographic microscopy show that the adaptive step-size strategy
significantly improves the stability and robustness of the reconstruction towards
noise yet retains the fast initial convergence speed of PIE and ePIE. More
importantly, the proposed approach is simple, nonparametric, and does not require
any preknowledge about the noise statistics. The great performance and limited
computational complexity make it a very attractive and promising technique for
robust Fourier ptychographic microscopy under noisy conditions.
PMID- 27607677
TI - Suppression of resonance Raman scattering via ground state depletion towards sub
diffraction-limited label-free microscopy.
AB - We report on the first experimental demonstration of the suppression of
spontaneous Raman scattering via ground state depletion. The concept of Raman
suppression can be used to achieve sub-diffraction-limited resolution in label
free microscopy by exploiting spatially selective signal suppression when imaging
a sample with a combination of Gaussian- and donut-shaped beams and
reconstructing a resolution-enhanced image from this data. Using a nanosecond
pulsed laser source with an emission wavelength of 355 nm, the ground state of
tris(bipyridine)ruthenium(II) molecules solved in acetonitrile was depleted and
the spontaneous Raman scattering at 355 nm suppressed by nearly 50 %. Based on
spectroscopic data retrieved from our experiment, we modeled the Raman image of a
scattering center in order to demonstrate the applicability of this effect for
superresolution Raman microscopy.
PMID- 27607678
TI - Steerable THz pulses from thin emitters via optical pulse-front tilt.
AB - A new method of steering THz pulses radiated from a thin emitter excited by
tilted optical pulse-fronts has been developed theoretically and validated in a
proof-of-concept experiment. This steering technique is potentially efficient and
rapid, and it should benefit from a THz-pulse energy that can scale with optical
beam size and magnitude. Conversely, the method employed for measuring the
steered THz pulses is also capable of characterizing the pulse-front tilt of an
optical beam.
PMID- 27607679
TI - Practical round-robin differential phase-shift quantum key distribution.
AB - Recently, a novel protocol named round-robin differential phase-shift (RRDPS)
quantum key distribution [Nature 509, 475(2014)] has been proposed. It can
estimate information leakage without monitoring bit error rate. In this paper, we
study the performance of RRDPS using heralded single photon source (HSPS) without
and with decoy-state method, then compare it with the performance of weak
coherent pulses (WCPs). From numerical simulation, we can see that HSPS performs
better especially for shorter packet and higher bit error rate. Moreover, we
propose a general theory of decoy-state method for RRDPS protocol based on only
three decoy states and one signal state. Taking WCPs as an example, the three
intensity decoy-state protocol can distribute secret keys over a distance of 128
km when the length of pulses packet is 32, which confirms great practical
interest of our method.
PMID- 27607680
TI - Graphene mode-locked femtosecond Cr2+:ZnS laser with ~300 nm tuning
range.
AB - Graphene has proved to be an excellent broadband saturable absorber for mode
locked operation of ultrafast lasers. However, for the mid-infrared (mid-IR)
range where broadly tunable sources are in great needs, graphene-based broadly
tunable ultrafast mid-IR lasers have not been demonstrated so far. Here, we
report on passive mode-locking of a mid-IR Cr:ZnS laser by utilizing a
transmission-type monolayer graphene saturable absorber and broad spectral
tunability between 2120 nm and 2408 nm, which is the broadest tuning bandwidth
ever reported for graphene mode-locked mid-IR solid-state lasers. The recovery
time of the saturable absorber is measured to be ~2.4 ps by pump-probe technique
at a wavelength of 2350 nm. Stably mode-locked Cr:ZnS laser delivers Fourier
transform-limited 220-fs pulses with a pulse energy of up to 7.8 nJ.
PMID- 27607681
TI - Broadband 7-fs diffractive-optic-based 2D electronic spectroscopy using hollow
core fiber compression.
AB - We demonstrate noncollinear coherent two-dimensional (2D) electronic spectroscopy
for which broadband pulses are generated in an argon-filled hollow-core fiber
pumped by a 1-kHz Ti:Sapphire laser. Compression is achieved to 7 fs duration (TG
FROG) using dispersive mirrors. The hollow fiber provides a clean spatial profile
and smooth spectral shape in the 500-700 nm region. The diffractive-optic-based
design of the 2D spectrometer avoids directional filtering distortions and
temporal broadening from time smearing. For demonstration we record data of
cresyl-violet perchlorate in ethanol and use phasing to obtain broadband
absorptive 2D spectra. The resulting quantum beating as a function of population
time is consistent with literature data.
PMID- 27607682
TI - Resolution improvements in integral microscopy with Fourier plane recording.
AB - Integral microscopes (IMic) have been recently developed in order to capture the
spatial and the angular information of 3D microscopic samples with a single
exposure. Computational post-processing of this information permits to carry out
a 3D reconstruction of the sample. By applying conventional algorithms, both
depth and also view reconstructions are possible. However, the main drawback of
IMic is that the resolution of the reconstructed images is low and axially
heterogeneous. In this paper, we propose a new configuration of the IMic by
placing the lens array not at the image plane, but at the pupil (or Fourier)
plane of the microscope objective. With this novel system, the spatial resolution
is increased by factor 1.4, and the depth of field is substantially enlarged. Our
experiments show the feasibility of the proposed method.
PMID- 27607683
TI - Image interpolation for division of focal plane polarimeters with intensity
correlation.
AB - Division of focal plane (DoFP) polarimeters operate by integrating micro
polarizer elements with a focal plane. These polarization imaging sensors reduce
spatial resolution output and each pixel has a varying instantaneous field of
view (IFoV). These drawbacks can be mitigated by applying proper interpolation
methods. In this paper, we present a new interpolation method for DoFP
polarimeters by using intensity correlation. We employ the correlation of
intensity measurements in different orientations to detect edges and then
implement interpolation along edges. The performance of the proposed method is
compared with several previous methods by using root mean square error (RMSE)
comparison and visual comparison. Experimental results showed that our proposed
method can achieve better visual effects and a lower RMSE than other methods.
PMID- 27607684
TI - Wafer scale fabrication of highly dense and uniform array of sub-5 nm nanogaps
for surface enhanced Raman scatting substrates.
AB - Metallic nanogap is very important for a verity of applications in plasmonics.
Although several fabrication techniques have been proposed in the last decades,
it is still a challenge to produce uniform nanogaps with a few nanometers gap
distance and high throughput. Here we present a simple, yet robust method based
on the atomic layer deposition (ALD) and lift-off technique for patterning
ultranarrow nanogaps array. The ability to accurately control the thickness of
the ALD spacer layer enables us to precisely define the gap size, down to sub-5
nm scale. Moreover, this new method allows to fabricate uniform nanogaps array
along different directions densely arranged on the wafer-scale substrate. It is
demonstrated that the fabricated array can be used as an excellent substrate for
surface enhanced Raman scatting (SERS) measurements of molecules, even on
flexible substrates. This uniform nanogaps array would also find its applications
for the trace detection and biosensors.
PMID- 27607685
TI - Miniaturized power limiter metasurface based on Fano-type resonance and Babinet
principle.
AB - In this work, we present a miniaturize power limiter, a device with size smaller
than that required by the working frequency, made of coupled self-complementary
electric inductive-capacitive (CELC) resonator and original electric inductive
capacitive (ELC) structure. We also make use of Babinet principle to ensure both
CELC and ELC are resonating at the same frequency. The CELC structure is loaded
with a Schottky diode to achieve the effect of a nonlinear power limiter. The
constructive interference of CELC and ELC structure produces a new Fano-type
resonance peak at a lower frequency. The Fano peak is sharp and able to
concentrate electric field at a region between the inner and outer metallic patch
of the metastructure, hence enhancing the nonlinear properties of the loaded
diode. The Fano peak enhances the maximum isolation of the power limiter due to
the local field enhancement at where the diode is loaded. Numerical simulation
and experiment are conducted in the S-band frequency to verify the power limiting
effect of the device designed and to discuss the formation of Fano peak. The
power limiter designed has a maximum isolation of 8.4 dB and a 3-dB isolation
bandwidth of 6%.
PMID- 27607686
TI - High-Q silk fibroin whispering gallery microresonator.
AB - We have experimentally demonstrated an on-chip all-silk fibroin whispering
gallery mode microresonator by using a simple molding and solution-casting
technique. The quality factors of the fabricated silk protein microresonators are
on the order of 105. A high-sensitivity thermal sensor was realized in
this silk fibroin microtoroid with a sensitivity of -1.17 nm/K, that is 8 times
higher than previous WGM resonator-based thermal sensors. This opens the way to
fabricate biodegradable and biocompatible protein based microresonators on a
flexible chip for biophotonics applications.
PMID- 27607687
TI - Leaky-mode waveguide modulators with high deflection angle for use in holographic
video displays.
AB - Film display holograms typically diffract light over a wide enough view-angle to
be viewed, directly, without intervening optics. However, all holographic video
displays (with the exception of eye-tracked systems) must use optics beyond the
hologram surface to overcome the challenges of small display extent and low
diffraction angle by using some form of demagnification and derotation (i.e.
angle magnification and optical multiplexing). We report a leaky mode waveguide
spatial light modulator with sufficiently high angular diffraction to obviate the
need for demagnification in scanned aperture systems. This high angle was
achieved by performing a number of experiments to determine the depth of the
annealed, proton-exchanged waveguide which corresponded to a maximized diffracted
angle. Diffraction sweeps were recorded in excess of 19.5 degrees (corresponding
to only 70 MHz of input bandwidth) for 632.8 nm light which is above the 15
degrees required for direct view display. Device geometries are proposed which
might achieve greater than 20 degrees of total angular sweep for red, green, and
blue light.
PMID- 27607688
TI - Investigation of surface damage precursor evolutions and laser-induced damage
threshold improvement mechanism during Ion beam etching of fused silica.
AB - Surface damage precursor evolution has great influence on laser-induced damage
threshold improvement of fused silica surface during Ion beam etching. In this
work, a series of ion sputtering experiment are carried out to obtain the
evolutions of damage precursors (dot-form microstructures, Polishing-Induced
Contamination, Hertz scratches, and roughness). Based on ion sputtering theory,
surface damage precursor evolutions are analyzed. The results show that the dot
form microstructures will appear during ion beam etching. But as the ion beam
etching depth goes up, the dot-form microstructures can be mitigated. And ion
beam etching can broaden and passivate the Hertz scratches without increasing
roughness value. A super-smooth surface (0.238nm RMS) can be obtained finally.
The relative content of Fe and Ce impurities both significantly reduce after ion
beam etching. The laser-induced damage threshold of fused silica is improved by
34% after ion beam etching for 800nm. Research results can be a reference on
using ion beam etching process technology to improve laser-induced damage
threshold of fused silica optics.
PMID- 27607689
TI - Precise measurement of micro bubble resonator thickness by internal aerostatic
pressure sensing.
AB - We develop a new, simple and non-destructive method to precisely measure the
thickness of thin wall micro bubble resonators (MBRs) by using internal
aerostatic pressure sensing. Measurement error of 1% at a bubble wall thickness
of 2 MUm is achieved. This method is applicable to both thin wall and thick wall
MBR with high measurement accuracy.
PMID- 27607690
TI - Super-sensitivity multiphoton frequency-domain fluorescence lifetime imaging
microscopy.
AB - We present a series of experiments that demonstrate a super-sensitive chemical
imaging technique based on multiphoton frequency-domain fluorescence lifetime
imaging microscopy (MPM-FD-FLIM) that shows a 2* improvement in imaging speed
compared to the theoretical limit of conventional MPM-FD-FLIM. Additionally, this
technique produces unprecedented sensitivity over a large range of fluorescence
lifetimes. These results are achieved through simple modifications to data
analysis in a conventional MPM-FD-FLIM microscope and are based on an analytical
model describing the signal-to-noise ratio (SNR) of a MPM-FD-FLIM system [J. Opt.
Soc. Am. A33, B1 (2016)]. Here we experimentally validate this model.
PMID- 27607691
TI - Imaging theory of structured pump-probe microscopy.
AB - With sub-micron spatial resolution and femtosecond temporal resolution, pump
probe microscopy provides a powerful spectroscopic probe of complex electronic
environments in bulk and nanoscale materials. However, the electronic structure
of many materials systems are governed by compositional and morphological
heterogeneities on length scales that lie below the diffraction limit. We have
recently demonstrated Structured Pump Probe Microscopy (SPPM), which employs a
patterned pump excitation field to provide spectroscopic interrogation of sub
diffraction limited sample volumes. Herein, we develop the imaging theory of SPPM
in two dimensions to accompany the previously published experimental methodology.
We show that regardless of pump and probe wavelengths, a nearly two-fold
reduction in spectroscopic probe volume can be achieved. We also examine the
limitations of the approach, with a detailed discussion of ringing in the point
spread function that can reduce imaging performance.
PMID- 27607693
TI - Highly tunable heterogeneously integrated III-V on silicon sampled-grating
distributed Bragg reflector lasers operating in the O-band.
AB - We report on the design, fabrication and performance of the first hetero
integrated III-V on silicon sampled-grating distributed Bragg reflector lasers
(SGDBR) operating in the O-band and based on direct bonding and adiabatic
coupling. Two devices with different geometric parameters are presented both
showing an output power in the Si waveguide as high as 7.5 mW and a continuous
tuning range of 27 and 35 nm respectively with a side mode suppression ration
higher than 35 dB.
PMID- 27607692
TI - Light-sheet microscopy with digital Fourier analysis measures transport
properties over large field-of-view.
AB - Using light-sheet microscopy combined with digital Fourier methods we probe the
dynamics of colloidal samples and DNA molecules. This combination, referred to as
selective-plane illumination differential dynamic microscopy (SPIDDM), has the
benefit of optical sectioning to study, with minimal photobleaching, thick
samples allowing us to measure the diffusivity of colloidal particles at high
volume fractions. Further, SPIDDM exploits the inherent spatially-varying
thickness of Gaussian light-sheets. Where the excitation sheet is most focused,
we capture high spatial frequency dynamics as the signal-to-background is high.
In thicker regions, we capture the slower dynamics as diffusion out of the sheet
takes longer.
PMID- 27607694
TI - A broadband tapered nanocavity for efficient nonclassical light emission.
AB - We present the design of a tapered nanocavity, obtained by sandwiching a photonic
wire section between a planar gold reflector and a few-period Bragg mirror
integrated into the tapered wire. Thanks to its ultrasmall mode volume (0.71
lambda3/n3), this hybrid nanocavity largely enhances the
spontaneous emission rate of an embedded quantum dot (Purcell factor: 6), while
offering a wide operation bandwidth (full-width half-maximum: 20 nm). In
addition, the top tapered section shapes the cavity far-field emission into a
very directive output beam, with a Gaussian spatial profile. For realistic taper
dimensions, a total outcoupling efficiency to a Gaussian beam of 0.8 is
predicted. Envisioned applications include bright sources of non-classical states
of light, such as widely tunable sources of indistinguishable single photons and
polarization-entangled photon pairs.
PMID- 27607695
TI - Advanced optical interference filters based on metal and dielectric layers.
AB - In this paper, we investigate the design and the fabrication of an advanced
optical interference filter based on metal and dielectric layers. This filter
respects the specifications of the 2016 OIC manufacturing problem contest. We
study and present all the challenges and solutions that allowed achieving a low
deviation between the fabricated prototype and the target.
PMID- 27607696
TI - Exciton localization and ultralow onset ultraviolet emission in ZnO nanopencils
based heterojunction diodes.
AB - n-GaN/i-ZnO/p-GaN double heterojunction diodes were constructed by vertically
binding p-GaN wafer on the tip of ZnO nanopencil arrays grown on n-GaN/sapphire
substrates. An increased quantum confinement in the tip of ZnO nanopencils has
been verified by photoluminescence measurements combined with quantitative
analyses. Under forward bias, a sharp ultraviolet emission at ~375 nm due to
localized excitons recombination can be observed in ZnO. The electroluminescence
mechanism of the studied diode is tentatively elucidated using a simplified
quantum confinement model. Additionally, the improved performance of the studied
diode featuring an ultralow emission onset, a good operation stability and an
enhanced ultraviolet emission shows the potential of our approach. This work
provides a new route for the design and development of ZnO-based excitonic
optoelectronic devices.
PMID- 27607697
TI - Towards correcting atmospheric beam wander via pump beam control in a down
conversion process.
AB - Correlated photon pairs produced by a spontaneous parametric down conversion
(SPDC) process can be used for secure quantum communication over long distances
including free space transmission over a link through turbulent atmosphere. We
experimentally investigate the possibility to utilize the intrinsic strong
correlation between the pump and output photon spatial modes to mitigate the
negative targeting effects of atmospheric beam wander. Our approach is based on a
demonstration observing the deflection of the beam on a spatially resolved array
of single photon avalanche diodes (SPAD-array).
PMID- 27607698
TI - Separation of multiple images via directional guidance using structured prism and
pyramid arrays.
AB - We propose a new concept of separating images through a directional guide of
multi-visuals by using structured prism or pyramid arrays. By placing prism
arrays onto two different image arrays, the two collective images below the
facets are guided to different directions. Using optical calculations, we
identify a condition for successful image separation. Transparent pyramid arrays
are used to separate four images into four directions. The direction of refracted
rays can be controlled by the refractive index of prisms and liquid filled into
the voids. In addition, the images can be switched by stretching and releasing an
elastomeric prism array.
PMID- 27607699
TI - Burst-mode-operated, sub-nanosecond fiber MOPA system incorporating direct seed
packet shaping.
AB - We report a novel burst-mode-operated sub-nanosecond fiber Master Oscillator,
Power Amplifier (MOPA) system incorporating direct seed-packet shaping without
external modulators. A fast digital-to-analog converter with 1 Gsps sampling rate
and 16 bit resolution was developed to control the pulse amplitudes and sequences
of a distributed feedback semiconductor seed laser to realize packet-shaped burst
mode operation. Optical pulses with durations as short as 700 ps and peak power
as high as 1 W can be generated from the seed by applying proper reverse voltages
after positive electrical pulses to the laser driver to cancel the residual
charges at its gate electrode. The average power of the laser can be amplified to
nearly 40 W with FWHM spectral linewidth of ~0.12 nm after three stages of
polarization maintaining fiber amplifiers. Different packet shapes including ramp
off, Gaussian, square and double rectangle can be produced from the fiber MOPA by
finely pre-shaping the seed pulse bursts. It is believed that such a laser has
provided a cost-effective solution to the generation of pulse bursts with
arbitrary packet shapes for different practical applications including material
micromachining and nonlinear frequency conversion.
PMID- 27607700
TI - Quantum detector tomography of a single-photon frequency upconversion detection
system.
AB - We experimentally presented a full quantum detector tomography of a synchronously
pumped infrared single-photon frequency upconversion detector. A maximum
detection efficiency of 37.6% was achieved at the telecom wavelength of 1558 nm
with a background noise about 1.0 * 10-3 counts/pulse. The
corresponding internal quantum conversion efficiency reached as high as 84.4%.
The detector was then systematically characterized at different pump powers to
investigate the quantum decoherence behavior. Here the reconstructed positive
operator valued measure elements were equivalently illustrated with the Wigner
function formalism, where the quantum feature of the detector is manifested by
the presence of negative values of the Wigner function. In our experiment,
pronounced negativities were attained due to the high detection efficiency and
low background noise, explicitly showing the quantum feature of the detector.
Such quantum detector could be useful in optical quantum state engineering,
quantum information processing and communication.
PMID- 27607701
TI - Optimization algorithm based characterization scheme for tunable semiconductor
lasers.
AB - In this paper, an optimization algorithm based characterization scheme for
tunable semiconductor lasers is proposed and demonstrated. In the process of
optimization, the ratio between the power of the desired frequency and the power
except of the desired frequency is used as the figure of merit, which
approximately represents the side-mode suppression ratio. In practice, we use
tunable optical band-pass and band-stop filters to obtain the power of the
desired frequency and the power except of the desired frequency separately. With
the assistance of optimization algorithms, such as the particle swarm
optimization (PSO) algorithm, we can get stable operation conditions for tunable
lasers at designated frequencies directly and efficiently.
PMID- 27607702
TI - Effect of two-dimensional confinement on switching of vertically aligned liquid
crystals by an in-plane electric field.
AB - We investigated the two-dimensional (2-D) confinement effect of liquid crystals
(LCs) on the switching of vertically aligned LCs by an in-plane electric field.
When an in-plane field is applied to a vertical alignment (VA) cell, virtual
walls are built at the center of the interdigitated electrodes and at the middle
of the gaps between them. The LC molecules are confined not only by the two
substrates but also by the virtual walls so that the turn-off time of a VA cell
driven by an in-plane field is dependent on the pitch of the interdigitated
electrodes as well as the cell gap. Therefore, the turn-off time of a VA cell
driven by an in-plane field can be reduced simply by decreasing the pitch of the
interdigitated electrodes as a result of the enhanced anchoring provided by the
virtual walls. The experimental results showed good agreement with a simple model
based on the 2-D confinement effect of LCs.
PMID- 27607703
TI - Multilevel recording of complex amplitude data pages in a holographic data
storage system using digital holography.
AB - A holographic data storage system using digital holography is proposed to record
and retrieve multilevel complex amplitude data pages. Digital holographic
techniques are capable of modulating and detecting complex amplitude distribution
using current electronic devices. These techniques allow the development of a
simple, compact, and stable holographic storage system that mainly consists of a
single phase-only spatial light modulator and an image sensor. As a proof-of
principle experiment, complex amplitude data pages with binary amplitude and four
level phase are recorded and retrieved. Experimental results show the feasibility
of the proposed holographic data storage system.
PMID- 27607704
TI - Integrated optic polarization splitter based on total internal reflection from a
birefringent polymer.
AB - An integrated optic polarization splitter with large fabrication tolerance and
high reliability is required for optical signal processing in quantum-encrypted
communication systems. A polarization splitter based on total internal reflection
from a highly birefringent polymer-reactive mesogen-is proposed and demonstrated
in this work. The device consists of a mode expander for reducing the wave vector
distribution of the guided mode, and an interface with a large birefringence.
Several polymers with suitable refractive indexes were used for fabricating the
device. We obtained a polarization splitter with a low crosstalk (less than -30
dB), and a large fabrication tolerance.
PMID- 27607705
TI - Bidirectional operation of 100 fs bound solitons in an ultra-compact mode-locked
fiber laser.
AB - We report on the experimental observation of bidirectional 100-fs bound solitons
from a nanotube-mode-locked dispersion-managed Er-fiber laser with an ultra
simple linear cavity. Two mode-locked pulse trains in opposite directions are
delivered simultaneously from the linear cavity. Under the pump power of <74 mW,
both the bidirectional outputs of the laser work at the single-soliton state with
pulse duration of 173 fs and 182 fs, respectively. Once the pump power is more
than 74 mW, both the bidirectional outputs evolve into the two-soliton bound
states with soliton separation of 1.53 ps. Interestingly, the bidirectional
operations can show the different bound states, i.e. the forward bound solitons
with phase difference of + pi/2, and the backward ones with phase difference of
pi/2. This is, to the best of our knowledge, the first demonstration of such
compact bidirectional soliton fiber laser with the sub-200 fs pulses.
PMID- 27607706
TI - Accurate theoretical and experimental characterization of optical grating
coupler.
AB - Periodic structures, acting as reflectors, filters, and couplers, are a
fundamental building block section in many optical devices. In this paper, a
three-dimensional simulation of a grating coupler, a well-known periodic
structure, is conducted. Guided waves and leakage characteristics of an out-of
plane grating coupler are studied in detail, and its coupling efficiency is
examined. Furthermore, a numerical calibration analysis is applied through a
commercial software package on the basis of a full-wave finite-element method to
calculate the complex propagation constant of the structure and to evaluate the
radiation pattern. For experimental evaluation, an optimized grating coupler is
fabricated using electron-beam lithography technique and plasma etching. An
excellent agreement between simulations and measurements is observed, thereby
validating the demonstrated method.
PMID- 27607707
TI - 1.3-MUm InAs quantum-dot micro-disk lasers on V-groove patterned and unpatterned
(001) silicon.
AB - We report comparison of lasing dynamics in InAs quantum dot (QD) micro-disk
lasers (MDLs) monolithically grown on V-groove patterned and planar Si (001)
substrates. TEM characterizations reveal abrupt interfaces and reduced threading
dislocations in the QD active regions when using the GaAs-on-V-grooved-Si
template. The improved crystalline quality translates into lower threshold power
in the optically pumped continuous-wave MDLs. Concurrent evaluations were also
made with devices fabricated simultaneously on lattice-matched GaAs substrates.
Lasing behaviors from 10 K up to room temperature have been studied
systematically. The analyses spotlight insights into the optimal epitaxial scheme
to achieve low-threshold lasing in telecommunication wavelengths on exact Si
(001) substrates.
PMID- 27607708
TI - Brillouin optical time-domain analyzer based on orthogonally-polarized four-tone
probe wave.
AB - The tolerance of the non-local effect in the BOTDA method using a dual-tone probe
wave with fixed frequency separation is theoretically and experimentally
investigated in this paper. The presented analysis points out that when the
sensing fiber consists of two long fiber segments with large BFS difference (>
100 MHz), there will always be only one probe tone interacting with the pump
pulse in the front fiber segment. Therefore, although the pulse distortion
problem can still be overcome in this case, the conventional non-local effect
would impose systematic error on the estimated BFS of the hotspot located at the
end of the front fiber segment. For the purpose of avoiding the impact of non
local effect and eliminating the pump distortion problem simultaneously when
using high probe power, a novel method based on a four-tone probe wave is
proposed, in which the probe light consists of two pairs of orthogonally
polarized dual-tone probe waves with opposite frequency scanning direction. The
experimental results demonstrate that the proposed method is capable of realizing
2 m spatial resolution over 104-km-long sensing fiber without the impact of non
local effect.
PMID- 27607709
TI - Optical generation of single-cycle 10 MW peak power 100 GHz waves.
AB - We demonstrate the generation of 100 GHz single-cycle pulses with up to 10 MW of
peak power using optical rectification and broadband phase matching via the
tilted pulse front (TPF) technique in lithium niobate. The optical driver is a
cryogenically cooled Yb:YAG amplifier providing tens of mJ energy, ~5 ps long
laser pulses. We obtain a high THz pulse energy up to 65 uJ with 31.6 MV/m peak
electric field when focused close to its diffraction limit of 2.5 mm diameter. A
high optical-to-THz energy conversion efficiency of 0.3% at 85 K is measured in
agreement with numerical simulations. This source is of great interest for a
broad range of applications, such as nonlinear THz field-matter interaction and
charged particle acceleration for ultrafast electron diffraction and table-top X
ray sources.
PMID- 27607710
TI - Analytical computation of the derivative of PSF for the optimization of phase
mask in wavefront coding system.
AB - Wavefront coding system can realize defocus invariance of PSF/OTF with a phase
mask inserting in the pupil plane. Ideally, the derivative of the PSF/OTF with
respect to defocus error should be close to zero as much as possible over the
extended depth of field/focus for the wavefront coding system. In this paper, we
propose an analytical expression for the computation of the derivative of PSF.
With this expression, the derivative of PSF based merit function can be used in
the optimization of the wavefront coding system with any type of phase mask and
aberrations. Computation of the derivative of PSF using the proposed expression
and FFT respectively are compared and discussed. We also demonstrate the
optimization of a generic polynomial phase mask in wavefront coding system as an
example.
PMID- 27607711
TI - 2.3 um range InP-based type-II quantum well Fabry-Perot lasers heterogeneously
integrated on a silicon photonic integrated circuit.
AB - Heterogeneously integrated InP-based type-II quantum well Fabry-Perot lasers on a
silicon waveguide circuit emitting in the 2.3 um wavelength range are
demonstrated. The devices consist of a "W"-shaped InGaAs/GaAsSb multi-quantum
well gain section, III-V/silicon spot size converters and two silicon Bragg
grating reflectors to form the laser cavity. In continuous-wave (CW) operation,
we obtain a threshold current density of 2.7 kA/cm2 and output power
of 1.3 mW at 5 degrees C for 2.35 MUm lasers. The lasers emit over 3.7 mW of
peak power with a threshold current density of 1.6 kA/cm2 in pulsed
regime at room temperature. This demonstration of heterogeneously integrated
lasers indicates that the material system and heterogeneous integration method
are promising to realize fully integrated III-V/silicon photonics spectroscopic
sensors in the 2 um wavelength range.
PMID- 27607712
TI - 140 W Cr:ZnSe laser system.
AB - We report a significant breakthrough in the development of fiber-pumped high
power CW laser systems based on Cr2+:ZnS and Cr2+:ZnSe gain
media. We demonstrate output power levels of up to 140 W near 2500 nm, and 32 W
at 2940 nm with corresponding optical efficiencies of 62% and 29%. Our novel
approach is based on rapid simultaneous scanning of the collinear laser mode and
pump beam across the Cr:ZnS/Se gain element which allows us to virtually
eliminate thermal lensing effects and obtain unprecedented levels of output power
with very high optical-to-optical efficiency.
PMID- 27607713
TI - Chopper z-scan technique for elliptic Gaussian beams.
AB - This paper reports an improvement to the chopper z-scan technique for elliptic
Gaussian beams. This improvement results in a higher sensitivity by measuring the
ratio of eclipsing time to rotating period (duty cycle) of a chopper that
eclipses the beam along the main axis. It is shown that the z-scan curve of the
major axis is compressed along the z-axis. This compression factor is equal to
the ratio between the minor and major axes. It was found that the normalized peak
valley difference with respect to the linear value does not depend on the axis
along which eclipsing occurs.
PMID- 27607714
TI - 0.52-11.86 Gbit/s OFDM modulation for power-sharing VLC transmission by using
VCSEL laser.
AB - In this paper, we propose employing a 682 nm vertical-cavity surface-emitting
laser (VCSEL) with 1 GHz bandwidth for high-speed and power-sharing wireless
visible light communication (VLC) in the different transmission distances of 2 to
5 m. In the measurement, the data rate of 0.52 to 11.86 Gbit/s (0.44 to 10.8
Gbit/s in a net data rate) can be achieved by using spectral-efficient orthogonal
frequency division multiplexing (OFDM) modulation with bit-loading algorithm.
Therefore, 4- to 256-quadrature amplitude modulations (QAMs) are employed
simultaneously in the modulation bandwidth for VCSEL-based VLC. The proposed
power-sharing VLC system can be divided to four end-users, when three beam
splitters (BSs) are used simultaneously. Moreover, all of the measured bit error
rates (BERs) are below the forward error correction (FEC) threshold (BER = 3.8 *
10-3).
PMID- 27607715
TI - Analysis of a random modulation single photon counting differential absorption
lidar system for space-borne atmospheric CO2 sensing.
AB - The ability to observe the Earth's carbon cycles from space provides scientists
an important tool to analyze climate change. Current proposed systems are mainly
based on pulsed integrated path differential absorption lidar, in which two high
energy pulses at different wavelengths interrogate the atmosphere sequentially
for its transmission properties and are back-scattered by the ground. In this
work an alternative approach based on random modulation single photon counting is
proposed and analyzed; this system can take advantage of a less power demanding
semiconductor laser in intensity modulated continuous wave operation, benefiting
from a better efficiency, reliability and radiation hardness. Our approach is
validated via numerical simulations considering current technological readiness,
demonstrating its potential to obtain a 1.5 ppm retrieval precision for 50 km
averaging with 2.5 W average power in a space-borne scenario. A major limiting
factor is the ambient shot noise, if ultra-narrow band filtering technology could
be applied, 0.5 ppm retrieval precision would be attainable.
PMID- 27607716
TI - Resolution and quality enhancement in terahertz in-line holography by sub-pixel
sampling with double-distance reconstruction.
AB - We demonstrate the enhancement of resolution and image quality in terahertz (THz)
lens-free in-line digital holography by sub-pixel sampling with double-distance
reconstruction. Multiple sub-pixel shifted low-resolution (LR) holograms recorded
by a pyroelectric array detector (100 MUm * 100 MUm pixel pitch, 124 * 124
pixels) are aligned precisely to synthesize a high-resolution (HR) hologram. By
this method, the lateral resolution is no more limited by the pixel pitch, and
lateral resolution of 150 MUm is obtained, which corresponds to 1.26lambda with
respect to the illuminating wavelength of 118.8 MUm (2.52 THz). Compared with
other published works, to date, this is the highest resolution in THz digital
holography when considering the illuminating wavelength. In addition, to suppress
the twin-image and zero-order artifacts, the complex amplitude distributions of
both object and illuminaing background wave fields are reconstructed
simultaneously. This is achieved by iterative phase retrieval between the double
HR holograms and background images at two recording planes, which does not
require any constraints on object plane or a priori knowledge of the sample.
PMID- 27607717
TI - Optical gain in capillary light guides filled with NaYF4:
Yb3+, Er3+ nanocolloids.
AB - A capillary light guide optical amplifier using nanocolloids of Yb3+
Er3+ co-doped NaYF4 as a filler was successfully
demonstrated. A 7-cm-long and 150-micron-inner-diameter capillary light guide was
capable to amplify a pulsed optical signal at 1550 nm with a gain coefficient of
0.15 cm-1 at a pump power of 4 mW (980-nm wavelength). The nanocolloid
gain medium was prepared by pulverizing the phosphor powder with a high-speed
planetary ball mill. Ball milling of the powder in water produced nanoparticles
with a size of approximately 130 nm that after drying were transferred to a
liquid with high refractive index (1.551 at 1550 nm) required to maintain light
confinement within the fused silica capillary light guide. The results show that
RE-doped colloids of nanocrystals can be potentially used as liquid gain media
fillers in capillary light guide lasers and amplifiers with high photostability
and low toxicity.
PMID- 27607718
TI - FPGA-based rate-adaptive LDPC-coded modulation for the next generation of optical
communication systems.
AB - In this paper, we propose a rate-adaptive FEC scheme based on LDPC codes together
with its software reconfigurable unified FPGA architecture. By FPGA emulation, we
demonstrate that the proposed class of rate-adaptive LDPC codes based on
shortening with an overhead from 25% to 42.9% provides a coding gain ranging from
13.08 dB to 14.28 dB at a post-FEC BER of 10-15 for BPSK transmission.
In addition, the proposed rate-adaptive LDPC coding combined with higher-order
modulations have been demonstrated including QPSK, 8-QAM, 16-QAM, 32-QAM, and 64
QAM, which covers a wide range of signal-to-noise ratios. Furthermore, we apply
the unequal error protection by employing different LDPC codes on different bits
in 16-QAM and 64-QAM, which results in additional 0.5dB gain compared to
conventional LDPC coded modulation with the same code rate of corresponding LDPC
code.
PMID- 27607719
TI - 70 dB long-pass filter on a nanophotonic chip.
AB - Integrated quantum photonic chips are promising for scalable, photonic based
quantum information processing. Although on-chip quantum photon sources and
single photon detectors have been demostrated separately, the full integration of
these components on single chip is hindered by the background photons from the
strong classical pump light. Here we design and fabricate an on-chip long-pass
filter which can provide 70 dB attenuation for visible light near 775 nm with
less than 3 dB insertion loss for light in the telecom C-band near 1550 nm. The
adiabatic design makes this device broadband and robust against fabrication
errors as well as working conditions. Combined with the previously demonstrated
non-classical on-chip source based on spontaneous parametric down conversion on
the same material system, this platform could enable 100 dB suppression of pump
light and holds promise in realizing fully integrated quantum photonic chips
where the sources, filters and detectors are monolithically integrated.
PMID- 27607720
TI - Propagation model for vector beams generated by metasurfaces.
AB - A propagation model of vector beams generated by metasurfaces based on vector
diffraction theory is established theoretically and verified experimentally.
Considering the Pancharatnam-Berry phase introduced by the metasurface,
analytical forms of vector beams for arbitrary incident polarization and
topological charge of metasurfaces are found in the Fresnel and Fraunhofer
diffraction regions, respectively. The complex amplitude of the resultant vector
beam can be described in terms of a confluent hypergeometric function, with an
intensity profile that manifests concentric rings in the Fresnel region and a
single ring in the Fraunhofer one. Fraunhofer diffraction provides a method to
create vector beams with simultaneously high purity and modal power. Further
experiments verify the theoretical results.
PMID- 27607721
TI - Novel method for increasing accuracy of projection moire contouring of large
surfaces.
AB - Projection moire is a high resolution, non-contact, full field method for
measuring out-of-plane displacements. Here, we develop a novel model for
projection moire system and derive a universal formula expressing the relation
between phase variation and out-of-plane displacement. In order to eliminate the
error caused by mismatching of pixels and changing of sensitivity coefficient, an
iterative algorithm is presented which expands measurements to the magnitude of
depth of field. Computer simulations and actual experiments prove the validity of
the proposed method.
PMID- 27607722
TI - Photothermal effects in ultra-precisely stabilized tunable microcavities.
AB - We study the mechanical stability of a tunable high-finesse microcavity under
ambient conditions and investigate light-induced effects that can both suppress
and excite mechanical fluctuations. As an enabling step, we demonstrate the ultra
precise electronic stabilization of a microcavity. We then show that photothermal
mirror expansion can provide high-bandwidth feedback and improve cavity stability
by almost two orders of magnitude. At high intracavity power, we observe self
oscillations of mechanical resonances of the cavity. We explain the observations
by a dynamic photothermal instability, leading to parametric driving of
mechanical motion. For an optimized combination of electronic and photothermal
stabilization, we achieve a feedback bandwidth of 500 kHz and a noise level of
1.1 * 10-13 m rms.
PMID- 27607723
TI - Optical modeling and optimizations of Cu2ZnSnSe4 solar
cells using the modified transfer matrix method.
AB - The fast and computationally inexpensive Modified Transfer Matrix Method (MTM) is
employed to simulate the optical response of kesterite
Cu2ZnSnSe4 solar cells. This method can partially take into
account the scattering effects due to roughness at the interfaces between the
layers of the stack. We analyzed the optical behavior of the whole cell structure
by varying the thickness of the TCO layer (iZnO + ITO) between 50 and 1200 nm and
the buffer CdS layer between 0 and 100 nm. We propose optimal combinations of the
TCO/CdS thicknesses that can locally maximize the device photocurrent. We provide
experimental data that qualitatively confirm our theoretical predictions.
PMID- 27607724
TI - Airborne compact rotational Raman lidar for temperature measurement.
AB - We developed an airborne compact rotational Raman lidar (CRL) for use on the
University of Wyoming King Air (UWKA) aircraft to obtain two-dimensional (2D)
temperature disman tributions. It obtained fine-scale 2D temperature
distributions within 3 km below the aircraft for the first time during the PECAN
(Plains Elevated Convection At Night) campaign in 2015. The CRL provided
nighttime temperature measurements with a random error of <0.5 K within 800 m
below aircraft at 45 m vertical and 1000 m horizontal resolution. The
temperatures obtained by the CRL and a radiosonde agreed. Along with water vapor
and aerosol measurements, the CRL provides critical parameters on the state of
the lower atmosphere for a wide range of atmospheric research.
PMID- 27607725
TI - Toward a planar black silicon technology for 50 MUm-thin crystalline silicon
solar cells.
AB - Auger and surface recombinations are major drawbacks that deteriorate a photon-to
electron conversion efficiencies in nanostructured (NS) Si solar cells. As an
alternative to conventional frontside nanostructuring, we report how backside
nanostructuring is beneficial for carrier collection during photovoltaic
operation that utilizes a 50-MUm-thin wafer. Ultrathin (4.3-nm-thin) zinc oxide
was also effective for providing passivated tunneling contacts at the
nanostructured backsides, which led to the enhancement of 24% in power conversion
efficiency.
PMID- 27607726
TI - Surface plasmon assisted hot electron collection in wafer-scale metallic
semiconductor photonic crystals.
AB - Plasmon assisted photoelectric hot electron collection in a metal-semiconductor
junction can allow for sub-bandgap optical to electrical energy conversion. Here
we report hot electron collection by wafer-scale Au/TiO2 metallic
semiconductor photonic crystals (MSPhC), with a broadband photoresponse below the
bandgap of TiO2. Multiple absorption modes supported by the 2D nano
cavity structure of the MSPhC extend the photon-metal interaction time and
fulfill a broadband light absorption. The surface plasmon absorption mode
provides access to enhanced electric field oscillation and hot electron
generation at the interface between Au and TiO2. A broadband sub
bandgap photoresponse centered at 590 nm was achieved due to surface plasmon
absorption. Gold nanorods were deposited on the surface of MSPhC to study
localized surface plasmon (LSP) mode absorption and subsequent injection to the
TiO2 catalyst at different wavelengths. Applications of these results
could lead to low-cost and robust photo-electrochemical applications such as more
efficient solar water splitting.
PMID- 27607727
TI - Design and modeling of a cost-effective achromatic Fresnel lens for concentrating
photovoltaics.
AB - This paper presents a novel Fresnel lens capable of significantly reducing
chromatic aberration in solar applications. The optical performance of this
achromatic lens has been analyzed through ray-tracing simulations, showing a
concentration factor three times higher than that attained by a classic silicone
on glass (SOG) Fresnel lens while maintaining the same acceptance angle. This
should avoid the need for a secondary optical element, reducing the cost
associated with its manufacturing and assembly and increasing the module
reliability. The achromatic lens is made of inexpensive plastic and elastomer
which allows a highly scalable and cost-competitive manufacturing process similar
to the one currently used for the fabrication of SOG Fresnel lenses.
PMID- 27607728
TI - Backscatter by azimuthally oriented ice crystals of cirrus clouds.
AB - The backscattering Mueller matrix has been calculated for the first time for the
hexagonal ice columns and plates with both zenith and azimuth preferential
orientations. The possibility of a vertically pointing polarization lidar
measuring the full Mueller matrix for retrieving the orientation distributions of
the crystals is considered. It is shown that the element m44 or,
equivalently, the circular depolarization ratio distinguishes between the low and
high zenith tilts of the crystals. Then, at their low or high zenith tilts,
either the element m22 or m34, respectively, should be
measured to retrieve the azimuth tilts.
PMID- 27607729
TI - Effect of scandium on the optical properties of crystalline silicon material.
AB - We have studied the optical properties of Sc-hyperdoped crystalline silicon based
on quantum calculations. We have designed several probable configurations and
found that the interstitial atomic positions of Sc (ScI,
ScSI, ScTI, ScHI) are stable in the silicon
matrix and can largely extend the absorption range of silicon from visible to
infrared. The sub-band gap light absorption is attributed to the change of band
structures of silicon and its intensity depends on the atomic concentration of Sc
in silicon. The special effect of Sc on the properties of silicon will extend the
sensitivity of silicon-based photodetectors to near infrared wavelength range.
PMID- 27607730
TI - Role of ytterbium-erbium co-doped gadolinium molybdate
(Gd2(MoO4)3:Yb/Er) nanophosphors in solar cells.
AB - Insufficient harvest of solar light energy is one of the obstacles for current
photovoltaic devices to achieve high performance. Especially, conventional
organic/inorganic hybrid solar cells (HSCs) based on PTB7 as p-type semiconductor
can only utilize 400-800 nm solar spectrum. One effective strategy to overcome
this obstacle is the introduction of up-conversion nanophosphors (NPs), in the
virtue of utilizing the near infrared region (NIR) of solar radiation. Up
conversion can convert low-energy photons to high-energy ones through multi
photon processes, by which the solar spectrum is tailored to well match the
absorptive domain of the absorber. Herein we incorporate erbium-ytterbium co
doped gadolinium molybdate (Gd2(MoO4)3, GMO),
denoted as GMO:Yb/Er, into TiO2 acceptor film in HSCs to enhance the
light harvest. Here Er3+ acts as activator while Yb-MoO4
2- is the joint sensitizer. Facts proved that the GMO:Yb/Er single
crystal NPs are capable of turning NIR photons to visible photons that can be
easily captured by PTB7. Studies on time-resolved photoluminescence demonstrate
that electron transfer rate at the interface increases sharply from 0.65 to 1.42
* 109 s-1. As a result, the photoelectric conversion
efficiency of the GMO:Yb/Er doped TiO2/PTB7 HSCs reach 3.67%, which is
increased by around 25% compared to their neat PTB7/TiO2 counterparts
(2.94%). This work may open a hopeful way to take the advantage of those
conversional rare-earth ion doped oxides that function in tailoring solar light
spectrum for optoelectronic applications.
PMID- 27607731
TI - Minimizing optical losses in monolithic perovskite/c-Si tandem solar cells with a
flat top cell.
AB - In a monolithic perovskite/c-Si tandem device, the perovskite top cell has to be
deposited onto a flat c-Si bottom cell without anti-reflective front side
texture, to avoid fabrication issues. We use optical simulations to analyze the
reflection losses that this induces. We then systematically minimize these losses
by introducing surface textures in combination with a so-called burial layer to
keep the perovskite top cell flat. Optical simulations show that, even with a
flat top cell, the monolithic perovskite/c-Si tandem device can reach a matched
photocurrent density as high as 19.57 mA/cm2.
PMID- 27607732
TI - Proton-Coupled Reduction of an Iron Cyanide Complex to Methane and Ammonia.
AB - Nitrogenase enzymes mediate the six-electron reductive cleavage of cyanide to CH4
and NH3 . Herein we demonstrate for the first time the liberation of CH4 and NH3
from a well-defined iron cyanide coordination complex, [SiP(iPr) 3 ]Fe(CN) (where
[SiP(iPr) 3 ] represents a tris(phosphine)silyl ligand), on exposure to proton
and electron equivalents. [SiP(iPr) 3 ]Fe(CN) additionally serves as a useful
entry point to rare examples of terminally-bound Fe(CNH) and Fe(CNH2 ) species
that, in accord with preliminary mechanistic studies, are plausible intermediates
of the cyanide reductive protonation to generate CH4 and NH3 . Comparative
studies with a related [SiP(iPr) 3 ]Fe(CNMe2 ) complex suggests the possibility
of multiple, competing mechanisms for cyanide activation and reduction.
PMID- 27607733
TI - Central metabolic nodes for diverse biochemical production.
AB - Central carbon metabolism is conserved among all organisms for cellular function
and energy generation. The connectivity of this metabolic map gives rises to key
metabolite nodes. Five of these nodes in particular, pyruvate, citric acid,
tyrosine and aspartate, acetyl-CoA, serve as critical starting points for the
generation of a broad class of relevant chemical molecules with ranging
applications from fuels, pharmaceuticals and polymer precursors. This review
highlights recent progress in converting these metabolite nodes into valuable
products. In particular, acetyl-CoA, the most well-connected node, serves as the
building block for several classes of molecules including fatty acids and
terpenes. Systematic metabolic engineering efforts focused on these metabolic
building blocks has enabled the production of industrially-relevant, biobased
compounds.
PMID- 27607739
TI - Dietary nitrite induces occludin nitration in the stomach.
AB - The clinical implications of the nitrate-nitrite-nitric oxide pathway have been
extensively studied in recent years. However, the physiological impact of
bioactive nitrogen oxides produced from dietary nitrate has remained largely
elusive. Here, we report a hitherto unrecognized nitrite-dependent nitrating
pathway that targets tight junction proteins in the stomach. Inorganic nitrate,
nitrite or saliva obtained after the consumption of lettuce were administered by
oral gavage to Wistar rats. The enterosalivary circulation of nitrate was allowed
to occur for 4 h after which the animals were euthanized and the stomach
collected. Nitrated occludin was detected by immunoprecipitation in the gastric
epithelium upon inorganic nitrite administration (p < .05) but was not observed
in the case of inorganic nitrate or human saliva administration. This
observation, along with differences in *NO production rates from inorganic and
salivary nitrite under simulated gastric conditions, suggests that competing
reactions at acidic pH determine the production of nitrating agents (*NO2) or
other, more stable, oxides. Accordingly, it is shown in vitro that salivary
nitrite yields higher steady state concentrations of *NO (0.37 +/- 0.01 MUM) than
sodium nitrite (0.12 +/- 0.03 MUM). Dietary-dependent reactions involving the
production of nitrogen oxides should be further investigated as, in the context
of occludin nitration, the consumption of green leafy vegetables (with high
nitrate content), if able to modulate gut barrier function, may have important
implications in the context of leaky gut disorders.
PMID- 27607734
TI - Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up
in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial.
AB - Importance: Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may
change over time following breast-conserving therapy. Objective: The EORTC "boost
no boost" trial showed that young age and high-grade invasive carcinoma were the
most important risk factors for IBTR. This study reanalyses pathological
prognostic factors related to IBTR using long-term follow-up. Design, Setting,
and Participants: Participants included 5569 early-stage breast cancer patients,
treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI),
who were randomized between no boost and a 16-Gy boost in the EORTC phase III
"boost no boost" trial (1989-1996). A total of 1616 patients with a
microscopically complete resection (according to local pathologists), included in
the central pathology review, have been analyzed in this study. Median follow-up
was 18.2 years. Interventions: No further treatment or 16-Gy boost, after BCS and
50-Gy WBI. Main Outcomes and Measures: Time to ipsilateral breast tumor
recurrence (IBTR) as first event. Results: The 20-year cumulative incidence of
IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age
(P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI,
1.36-3.38; P = .001) were associated with an increased risk of IBTR in
multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95%
CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40
years or younger, 41 to 50 years and 50 years or older, respectively (P < .001).
This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with
and without DCIS (P < .001). High-grade tumors relapsed more frequently early
during follow-up but the relative effect of age and presence of DCIS seemed
stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI,
22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high
risk patients (<=50 years with DCIS present). Conclusions and Relevance: The
association of high-grade invasive tumor with IBTR diminished during follow-up,
while the effect of DCIS adjacent to invasive tumor seemed to remain stable.
Therefore, patients with high-grade invasive tumors should be monitored closely,
especially in the first 5 years, while additional DCIS is an indication for
longer follow-up, emphasizing the importance of long-term trial follow-up to
estimate absolute effects accurately. Trial Registration: clinicaltrials.gov
Identifier: NCT02295033.
PMID- 27607740
TI - Hysteroscopic resection of type 3 myoma: a new challenge?
AB - OBJECTIVE: Type 3 myomas are intramural within contact with the endometrium but
lack any cavity deformation. There is no guideline for management of symptomatic
type 3 myoma. The aim of this study was to evaluate the feasibility of
symptomatic type 3 myoma hysteroscopic resection. METHOD: This retrospective
study included symptomatic women (mainly pain, infertility or bleeding) who
obtained an operative hysteroscopy for type 3 symptomatic myoma from June 2010 to
December 2014 in the gynaecological unit of a teaching hospital. RESULT: Thirteen
women with an operative resection using bipolar electrosurgery of type 3 myoma
during the study period (June 2010 to December 2014) were included in the study.
Two women had a hysterectomy 6 and 12 months after the procedure and one woman
had an open myomectomy 30 months after the procedure for the recurrence of
abnormal bleeding. Postoperative office hysteroscopy show a postoperative
synechiae in 3 women out of 8. Incomplete resection was also obtained in 3 women
out of 8. CONCLUSION: Hysteroscopic resection is a potential alternative to
traditional surgery for type 3 myoma. This procedure must be confined to skilled
surgeons because it is a difficult procedure. A postoperative office hysteroscopy
is recommended in women of reproductive age.
PMID- 27607741
TI - Suicidality in body dysmorphic disorder (BDD): A systematic review with meta
analysis.
AB - Although a considerable number of studies have indicated that the rates of
suicidal thoughts and behaviors in Body Dysmorphic Disorder (BDD) are high, no
systematic review has been undertaken to explore the strength and patterns of the
relationship between suicidality and BDD. This is the first systematic review and
meta-analysis which aimed to examine the association between BDD and suicidality
and the mechanisms underlying suicidality in BDD. Searches of five bibliographic
databases including Medline, PsychINFO, Embase, Web of Science and CINAHL, were
conducted from inception to June 2015. Seventeen studies were included in the
review. Meta-analyses were performed using random effect models to account for
the high levels of heterogeneity in the data. A positive and statistically
significant association was found between BDD and suicidality (OR=3.63, 95%
CI=2.62 to 4.63). Subgroup analyses showed that BDD was associated with increased
odds for both, suicide attempts (OR=3.30, 95% CI=2.18 to 4.43) and suicidal
ideation (OR=2.57, 95% CI=1.44 to 3.69). The evidence concerning suicide deaths
in BDD was scarce. BDD-specific factors and comorbid diagnoses of Axis I
disorders were likely to worsen suicidality in BDD. However, the modest number,
and the low methodological quality, of the studies included in this review
suggest caution the interpretation of these findings.
PMID- 27607742
TI - Context for Practice: Unavoidable Pressure Injuries, Adaptation to a Urinary
Diversion, LUTS in Women With Diabetes Mellitus.
PMID- 27607743
TI - Reducing Pressure Injury Incidence Using a Turn Team Assignment: Analysis of a
Quality Improvement Project.
AB - PURPOSE: The purpose of this study was to analyze outcomes of a quality
improvement project that evaluated a turning intervention for prevention of
facility-acquired pressure injuries. DESIGN: A descriptive correlational study
design examined the effectiveness of using a "turn team assignment" on pressure
injury incidence and staff perceptions. SUBJECTS AND SETTING: The study sample
comprised RNs and patient care associates assigned to provide care for patients
admitted on the first or any subsequent day of hospitalization to a surgical
intensive care unit at a Midwest inner-city teaching hospital. METHODS: Direct
observation by expert clinicians occurred in 2-hour increments over a 14-day
period using an 11-item, unit-designed process improvement tool. We collected
information regarding cueing, concurrent turning, independent turning in lieu of
the cue, staff support, and possible barriers to turning and repositioning. Staff
perceptions were collected using an online tool via survey. The survey utilized a
14-item questionnaire, and a 5-point Likert Scale to identify staff perceptions
and beliefs about the turn team intervention. Pressure injury occurrences were
measured using data from our monthly prevalence study. RESULTS: Pressure injury
occurrences declined from 24.9% to 16.8% over the data collection period. There
was a strong positive correlation between verbal cueing and turning (r = 0.815; P
< .05). Staff perceptions supported preintervention education (64.3%) and cueing
(93%; 78%) as effective interventions in completing patient turning. CONCLUSIONS:
Findings suggest that turn team assignments using verbal cueing are an effective
intervention that decreases pressure injury occurrence. This intervention
required no increase in staffing personnel, making this type of intervention
reasonable and effective in improving frequency of repositioning and decreasing
pressure injury prevalence rates.
PMID- 27607744
TI - The Impact of Smoking and Smoking Cessation on Wound Healing in Spinal Cord
Injured Patients With Pressure Injuries: A Retrospective Comparison Cohort Study.
AB - PURPOSE: The purpose of this study was to evaluate the impact of implementing
evidence-based guidelines on smoking cessation in persons with spinal cord
injuries and pressure injuries. We also evaluated the impact of smoking on
pressure injury healing in this population. SUBJECTS AND SETTING: The sample
population included 158 spinal cord-injured patients with pressure injuries (29
females and 129 males). There were 83 in the control group and 75 in the
intervention group, with a mean age of 44 years in both groups. The research
setting was an outpatient wound clinic located in a large medical center in the
southeastern United States. METHODS: A retrospective chart review was completed.
Data were reviewed 6 months before and 6 months after implementation of the US
Department of Health and Human Services Clinical Practice Guidelines for Treating
Tobacco Use and Dependence. We evaluated the number and size of wounds,
achievement of smoking cessation, and demographic information. RESULTS: Forty
eight percent of the control group participants and 57% of the intervention group
participants smoked cigarettes at baseline. Smoking cessation doubled with the
use of the clinical practice guidelines (P = .03). Smokers presented with a
greater number of pressure injuries than nonsmokers. They experienced a mean
increase rather than reduction in wound size. Nearly half (45.5%) of the
intervention group participants who desired to have surgery had it performed,
compared with only 34.9% of the control group participants (P = .35).
CONCLUSIONS: Our findings demonstrate a positive influence with use of clinical
practice guidelines to help individuals stop smoking. Results also confirm
findings of previous studies supporting the negative impact of smoking on
pressure injury healing in persons with spinal cord injuries.
PMID- 27607745
TI - Prevalence of Parastomal Hernia and Factors Associated With Its Development.
AB - PURPOSE: The purpose of this study was to identify risk factors for development
of a parastomal hernia (PH). DESIGN: Cross-sectional survey. SETTING AND
SUBJECTS: The target population comprised 2854 persons receiving services from
the Manitoba Ostomy Program. Seven hundred sixty-four responses were received,
yielding a response rate of 29.3%. Respondents average age was 70 years (SD =
12.8); 425 (55.6%) had a colostomy, 236 (30.8%) had an ileostomy, 63 (8.2%) had a
urostomy, and 40 (5.2%) indicated other types of stomas or fistula. INSTRUMENTS:
A questionnaire was developed by the authors that collected the following data:
demographics, relevant medical history, personal and lifestyle factors, surgery
related factors, pre- and postoperative care factors, and information about the
presence of a PH and physical and lifestyle effects related to a PH. Devices to
enable respondents to measure the size of their stoma and abdominal girth were
included in the survey package. The survey tool took approximately 30 to 45
minutes to complete. METHODS: An informational pamphlet and introductory letter
were mailed 2 weeks before the survey was mailed. This was followed by a reminder
letter. Bivariate analyses were completed in order to identify potential
associations between all variables and a diagnosis of a PH; multivariate analysis
was then completed to determine which factors were associated with an increased
likelihood of a PH. RESULTS: Significant univariate associations were found
between a diagnosis of a PH and diverticulitis, cirrhosis, benign prostatic
enlargement, previous diagnosis of hernia, a smoking history, type of ostomy,
stoma size, and continuous variables age and abdominal girth. Multiple regression
analysis indicated that patients who underwent stoma surgery for cancer had
larger stomas (1.5 to >3 in), and a colostomy were more likely to develop a PH.
CONCLUSIONS: The results of this study indicate that PHs are prevalent.
Additional research is needed to determine more effective intervention for
preventing and managing a PH.
PMID- 27607746
TI - Factors Related to Adaptation to Cystectomy With Urinary Diversion: An
Integrative Review.
AB - Patients with bladder (urothelial) cancer undergoing urinary diversion (UD)
experience physical changes that require important adjustments in their daily
lives. This integrative review aims to identify factors that influence adult
adaptation to life after cystectomy with the creation of a UD. A review of
primary research articles published between 1990 and 2014 was conducted using the
PubMed and CINAHL Plus electronic databases. Results of the studies were
summarized into 5 categories: (1) individual and family factors, (2) technical
aspects related to the individual's ability to care for his or her UD, (3)
perioperative nursing care, (4) educational needs, and (5) symptom experience.
Bladder cancer patients treated with a cystectomy with a UD have a complex set of
needs during postoperative adaptation to their reconstructed urinary system. This
integrative review summarizes existing knowledge of factors that affect
adaptation to a UD in patients with bladder cancer and may guide future studies.
Research on this is limited and more studies are needed.
PMID- 27607747
TI - Urinary Incontinence in Pregnant Women: Prevalence, Associated Factors, and Its
Effects on Health-Related Quality of Life.
AB - PURPOSE: The purpose of this study was to determine the prevalence of and risk
factors for urinary incontinence (UI) during pregnancy and to evaluate its effect
on health-related quality of life. DESIGN: Descriptive, cross-sectional study.
SUBJECTS AND SETTING: The sample of the study comprised 287 pregnant women
attending an outpatient clinic located in a research and training hospital in
Ankara, Turkey. METHODS: Data were collected using an investigator-developed
questionnaire that included 2 validated instruments, the International
Consultation on Incontinence Questionnaire Short Form and Incontinence Quality of
Life scale. RESULTS: The prevalence of UI in the study population was 21.3% (n =
61). Cumulative scores in pregnant women who "always" experienced UI and those
who expressed a "large amount" of UI were lower than women with milder UI.
Logistic regression analysis found associations between UI and age in years (odds
ratio [OR] = 3.833; 95% confidence interval [CI], 1.763-8.332), parity (OR =
2.539; 95% CI, 1.135-5.675), third trimester versus first trimester (OR = 3.206;
95% CI, 1.178-8.725), and prior use of hormonal contraceptives (OR = 0.209; 95%
CI, 0.085-0.513). CONCLUSIONS: Urinary incontinence is prevalent among pregnant
women. Age, parity, and gestational week were associated with an increased
likelihood of UI during pregnancy. Prior use of contraceptive hormones was
associated with a reduced risk of UI during pregnancy.
PMID- 27607748
TI - Prevalence of Fecal Incontinence in the Acute Care Setting.
AB - PURPOSE: The aim of this study was to determine the prevalence of fecal
incontinence (FI) and its associated risk factors in acutely ill adult
hospitalized patients. METHODS: A cross-sectional design was used to collect data
at 2 time points in 7 hospitals in the Midwestern United States. An investigator
developed tool was used by trained data collectors to identify pertinent patient
characteristics, the presence of FI, and potential associated factors. RESULTS:
The prevalence of FI in the 1083 patients assessed was 20% (n = 221). Prevalence
rates from the 7 individual hospitals ranged from 16% to 30%. Medications were
the most common associated factor (49%; n = 109), followed by neurologic diseases
(40%; n = 89), and bowel motility disorders (30%; n = 67). The majority of
patients with FI had stool consistency described as "loose unformed" (59%; n =
130) or "liquid" (25%; n = 55). Many patients had multiple potential risk factors
for FI; 48% (n = 107) had 1 associated factor, 37% (n = 82) had 2 associated
factors, and 8% (n = 18) had 3 or more associated factors. Age was associated
with an increased likelihood of FI; the chances for FI increase 1.7% with each
year of age. Unit type was also a significant associated with FI; patients
managed in the intensive care unit were 78% more likely to have FI as compared to
patients care for in a medical-rehabilitation unit. CONCLUSIONS: Fecal
incontinence is a common problem in hospitalized adult patients. Previously
identified risk factors were also found in our sample.
PMID- 27607749
TI - Lower Urinary Tract Symptoms in Women With Type 2 Diabetes Mellitus.
AB - PURPOSE: The aim of the study was to compare lower urinary tract symptoms (LUTS)
in women with and without type 2 diabetes mellitus (DM). SUBJECTS AND SETTING:
The sample was drawn from community-dwelling women in the province of Istanbul
who were cared for in the diabetes outpatient clinic of Istanbul Medical School
between January and June 2012. Two hundred forty-nine women with DM were compared
to 255 women without DM cared for in the obstetrics and gynecology department of
the same university hospital. The mean ages of the groups were 55.1 and 53.7
years, respectively. METHODS: Participants completed a questionnaire that queried
sociodemographic and clinical characteristics; the Bristol Female Lower Urinary
Tract Symptoms-Short Form (BFLUTS-SF) was used to evaluate LUTS. The
questionnaire required 10 to 15 minutes to complete; participants completed the
questionnaire in a private room of each of the respective outpatient clinics.
RESULTS: No statistically significant differences were found when groups (women
with and without DM) were compared based on age and cigarette smoking (P > .05).
In contrast, BMI scores were significantly higher in the women with DM (P <
.001). The cumulative BFLUTS scores and the filling and incontinence symptoms
subscale sores (P < .001) were significantly higher in women with DM. No
differences were observed in voiding symptoms (P = .347), sexual function (P =
.380), and health-related quality of life (P = .142) subscale scores. The
prevalence of storage symptoms nocturia, voiding frequency, urge incontinence,
stress incontinence, frequency of incontinent episodes were higher among women
with DM. In addition, women with DM were more likely to report the need to change
clothing because of urinary leakage, effect of incontinence on daily tasks, and
overall interference with daily activities of living. CONCLUSIONS: Women with
type 2 DM are more likely to experience LUTS as compared to women without DM.
Women with type 2 DM should routinely be assessed for LUTS.
PMID- 27607751
TI - Preparing for Success on the APRN WOC Examination.
PMID- 27607750
TI - Barriers to Communication With a Healthcare Provider and Health Literacy About
Incontinence Among Informal Caregivers of Individuals With Dementia.
AB - PURPOSE: The purpose of this study was to examine barriers to communicating with
healthcare professionals and health literacy about incontinence among different
types of informal caregivers of individuals with Alzheimer disease (AD). DESIGN:
Descriptive secondary analysis. SUBJECTS AND SETTING: The sample included 48
family/friend adult caregivers of individuals who had AD. Seventy-five percent
were female; their mean age was 64 +/- 14 years (mean +/- SD). Caregivers were
spouses (44%), daughters (31%), or extended family members/friends (25%). Nearly
half (48%) of caregivers had a racially or ethnically diverse background; 58% of
their care recipients had incontinence. METHODS: Data were collected via focus
groups, interviews, and written surveys. Verbal responses were audiotaped,
transcribed, and analyzed for themes by caregiver type using content analysis.
RESULTS: Caregivers of persons with AD described role-related barriers to
improving health literacy about incontinence and its management. Main themes of
barriers emerged for each type of role that were emotive in nature for daughters,
experiential for both spouse caregivers, system related for husbands, and
relational (being perceived as an outsider) for extended family/friends.
CONCLUSIONS: Nurse continence specialists have an important role in raising
health literacy about incontinence and its management for informal caregivers of
individual with AD. Results inform the development of interventions that are
tailored to the type of caregiver as recommended by national health literacy
initiatives with the aim of improving outcomes such as incontinence of care
recipients.
PMID- 27607752
TI - Efficacy of Dialkylcarbamoylchloride-Coated Dressing in Management of Colonized
or Infected Neonatal and Pediatric Wounds.
AB - BACKGROUND: Wound healing is a dynamic process that normally follows a
predictable cascade of events. A common cause of delayed wound healing or wound
dehiscence is increased colonization with microbes, often leading to infection.
Infection may impede the healing process by inducing an undesirable inflammatory
response. Systemic antibiotics and topical antiseptics are mainstays of
treatment, but their adverse side effects and the potential for emergence of
resistant microbial strains have led to a search for alternative approaches for
control of bioburden. CASES: We describe two neonates and one 10-year-old girl
who experienced delayed wound healing treated with a nonmedicated dressing that
exploits bacterial cell-surface hydrophobic interactions via a dressing with a
fatty acid (dialkylcarbamoylchloride [DACC]) coating. This dressing was used in a
colonized, unstageable occipital pressure injuries, an infected stage 4 pressure
injury over a vertebra, and a dehisced surgical sternal wound. Complete closure
was achieved in all wounds within 2 to 4 weeks. CONCLUSION: We employed a DACC
coated dressing that provides bacteriostatic activity without creating
cytotoxicity or an inflammatory response.
PMID- 27607753
TI - WOCN(r)-Accredited Professional Education Programs.
PMID- 27607754
TI - The VCU Pressure Ulcer Summit: The Search for a Clearer Understanding and More
Precise Clinical Definition of the Unavoidable Pressure Injury.
PMID- 27607755
TI - Interpreting Database Studies.
PMID- 27607756
TI - Promoting patient-centred palliative care: a scoping review of the patient
dignity question.
AB - PURPOSE OF REVIEW: In recent years, there has been a growing interest in
promoting dignity in care, and specific interventions have been developed to
include it at the end of life. The patient dignity question (PDQ) is a recent,
novel and simple intervention that healthcare professionals can implement;
however, little information is known about its impact. This scoping review aims
to examine and map out the PDQ literature. RECENT FINDINGS: Studies suggest that
patients, families and professionals have a positive view of the PDQ in that it
helps to get to know patients and provide them with the best care possible. The
PDQ seems to promote an environment of care focused on the person and the
prevalence of more human aspects in clinical encounters between professionals and
patients. This is especially so in situations in which human aspects of the
healthcare relationship at baseline received lower marks. Healthcare
professionals thought that performing the PDQ to determine what is important to
the patient is a feasible and effective exercise. SUMMARY: The published
literature suggests that PDQ is a beneficial intervention for approaching and
getting to know a patient as a person. More studies are needed that measure pre
post-PDQ changes and that demonstrate their impact on patient care.
PMID- 27607757
TI - Utility of endoscopic therapy using a double balloon endoscope combined with a
long-type ultra-slim endoscope in postoperative patient allergic to contrast
media (with video).
PMID- 27607758
TI - Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes
Using Iodonium Salts.
AB - Arylation, vinylation, and alkynylation of electron-deficient arenes and
heteroarenes have been achieved by chemoselective C-H zincation followed by
copper-catalyzed coupling reactions using iodonium salts. This approach offers a
direct and general access to a wide scope of (hetero)biaryls as well as
alkenylated and alkynylated heteroarenes under mild conditions. It is
particularly useful and valuable for the rapid and modular synthesis of diverse
(hetero)aryl compounds, as demonstrated in the synthesis of transient receptor
potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1
receptor) antagonists.
PMID- 27607761
TI - The WS2 quantum dot: preparation, characterization and its optical limiting
effect in polymethylmethacrylate.
AB - Due to the matching surface energy, WS2 quantum dots (QDs) can be obtained
through direct liquid exfoliation in N-methyl-2-pyrrolidone rather than an
ethanol and water mixture. Ultra-small WS2 QDs with a diameter of 2.4 nm are
fabricated by an ultrasound method followed by high speed centrifugation up to 10
000 rpm. An excellent nonlinear optical (NLO) property of the WS2 QD/
polymethylmethacrylate (PMMA) composite for the nanosecond pulsed laser at both
532 and 1064 nm has been measured. Results illustrate the lower onset thresholds
(F ON ), lower optical limiting thresholds (F OL ), and higher two-photon
absorption coefficient (beta) with respect to a higher concentration of embedded
WS2 QDs into the PMMA solid state matrix for both 532 and 1064 nm.
PMID- 27607762
TI - Ascending Aortic Endoballoon Occlusion Feasible Despite Moderately Enlarged Aorta
to Facilitate Robotic Mitral Valve Surgery.
AB - OBJECTIVE: Aortic occlusion with an endoballoon is a well-established technique
to facilitate robotic and minimally invasive mitral valve surgery. Use of the
endoballoon has several relative contraindications including ascending aortic
dilatation greater than 38 mm in size. We sought to review our experience using
the endoballoon in cases of totally endoscopic mitral valve surgery with aortic
diameters greater than 38 mm. METHODS: A retrospective review of our single-site
database was conducted to identify patients undergoing totally endoscopic mitral
valve surgery by a single surgeon using an endoballoon and who had ascending
aortic dilation. We defined aortic dilation as greater than 38 mm. Computed
tomography was done preoperatively on all patients to evaluate the aortic anatomy
as well as iliofemoral access vessels. Femoral artery cannulation was done in a
standardized fashion to advance and position the endoballoon, to occlude the
ascending aorta, and to deliver cardioplegia. RESULTS: From October 2011 through
June 2015, 196 patients underwent totally endoscopic mitral valve surgery using
an endoballoon at our institution. Twenty-two patients (11.2%) had ascending
aortic diameters greater than 38 mm (range, 38.1-46.6 mm; mean, 40.5 +/- 2.5 mm).
In these cases, there were no instances of aortic dissection or other injury due
to balloon rupture, balloon migration, device movement leading to loss of
occlusion, or inability to complete planned surgery due to occlusion failure.
CONCLUSIONS: Our experience suggests that it is possible to successfully use
endoaortic balloon occlusion in patients with ascending aortic dilation with
proper preoperative imaging and planning.
PMID- 27607763
TI - Sudoscan is an effective screening method for asymptomatic diabetic neuropathy in
Chinese type 2 diabetes mellitus patients.
AB - AIMS/INTRODUCTION: The aim of the present study was to use the sudomotor function
test, Sudoscan, as a screening method for the evaluation of asymptomatic diabetic
distal symmetric polyneuropathy in Chinese type 2 diabetes patients. As a result,
more attention could be paid to those asymptomatic patients who could be easily
neglected and underdiagnosed in everyday clinic. MATERIALS AND METHODS: A total
of 394 Chinese type 2 diabetes patients were enrolled and tested for symptoms and
clinical signs of neuropathy using the Neurological Symptom Score, Neuropathy
Disability Score, and vibration perception threshold. Sudoscan was carried out,
and the results were collected as the measurement of the electrochemical skin
conductance of both hands and feet. RESULTS: In the present study, we found that
the abnormal rate of Sudoscan results in patients with asymptomatic neuropathy
was higher than those without neuropathy and those with symptomatic neuropathy.
This study also showed that lower electrochemical skin conductance at the feet
was significantly associated with increasing symptoms, Neurological Symptom Score
(r = -0.124, P < 0.05), Neuropathy Disability Score (r = -0.3, P < 0.01) and
vibration perception threshold value (r = -0.18, P < 0.05). Logistic analysis
showed that age (odds ratio 1.042, 95% confidence interval 1.014-1.071, P < 0.05)
and feet electrochemical skin conductance levels (odds ratio 0.98, 95% confidence
interval 0.962-0.993, P < 0.01) were independently associated with diabetic
distal symmetric polyneuropathy. CONCLUSIONS: Sudoscan might be a promising tool
to screen asymptomatic diabetic distal symmetric polyneuropathy in Chinese
patients with type 2 diabetes mellitus.
PMID- 27607764
TI - Sexually transmissible infection and HIV prevention and treatment for young male
sex workers in Vietnam: findings from the SHEATH intervention.
AB - : Background Urban centres in Vietnam have high rates of HIV infection,
especially among men who have sex with men (MSM). A subgroup of MSM, young male
sex workers (YMSW), are at especially high risk due to concurrent sex with
multiple male and female partners, low levels of knowledge regarding HIV and
sexually transmissible infection (STI) transmission, and limited engagement with
health services, including STI and HIV screening and treatment. METHODS: A
targeted intervention (SHEATH) derived from Harm Reduction and Sexual Health
Promotion intervention technology was implemented in an out-of-treatment
population of YMSW in Hanoi and Ho Chi Minh City (n=919). RESULTS: YMSW reported
high levels of satisfaction with each of the seven core modules within the
intervention and for the intervention as a whole. The intervention conferred
significant benefit in relation to improved knowledge of STI and HIV transmission
(P<0.001). Although only 36% of participants had seen a healthcare provider in
the past year, following the intervention 81% intended to see one in the next 6
months. Similarly, although 71% of participants did not disclose that they were
MSM the last time they visited a healthcare provider, following the intervention
71% intended to do so at their next visit. High rates of STIs (>10%) and HIV
(9.5%) were also found. CONCLUSION: The data show that the SHEATH intervention
can be implemented in this population and setting, is met with high rates of
acceptability, and positively impacts STI and HIV knowledge and multiple health
services outcomes (including knowledge of HIV status and disposition towards
habituation of HIV screening).
PMID- 27607765
TI - Grief, traumatic stress, and posttraumatic growth in women who have experienced
pregnancy loss.
AB - OBJECTIVE: Pregnancy loss is common and can be devastating for those who
experience it. However, a historical focus on negative outcomes, and grief in
particular, has rendered an incomplete portrait of both the gravity of the loss,
and the potential for growth in its wake. Consistent with contemporary models of
growth following bereavement, this study explored the occurrence of posttraumatic
growth following pregnancy loss and further assessed the role of core belief
disruptions and common loss context factors across perinatal grief, posttraumatic
stress symptoms, and posttraumatic growth. METHOD: Women who had experienced a
miscarriage or stillbirth (N = 328) were recruited through perinatal loss support
groups and completed an online survey that assessed core belief disruption,
perinatal grief, posttraumatic stress symptoms, posttraumatic growth, loss
context factors, and demographics. Hypotheses were tested via hierarchical
multiple regression. RESULTS: All hypotheses were supported. Specifically, (a)
moderate levels of posttraumatic growth were reported; (b) core belief
disruptions predicted perinatal grief, posttraumatic stress symptoms, and
posttraumatic growth; and (c) perinatal grief predicted posttraumatic stress
symptoms and growth. CONCLUSION: Findings suggest that pregnancy loss can be a
traumatic event, that core belief disruptions play a significant role in
posttrauma outcomes, and that other factors may contribute to grief,
posttraumatic stress symptoms, and posttraumatic growth following pregnancy loss
that warrant further research (e.g., rumination). Despite potential
methodological and sampling limitations, the use of validated measures to assess
posttraumatic growth in a large sample represents a robust attempt to quantify
the occurrence of posttrauma change following pregnancy loss. (PsycINFO Database
Record
PMID- 27607766
TI - Improving assessment of race, ethnicity, and culture to further veteran PTSD
research.
AB - OBJECTIVE: Racial and ethnic disparities in posttraumatic stress disorder (PTSD)
and its treatment have been documented for both civilians and military veterans.
To better understand the presence of disparities and factors that might
contribute to them, accurate assessment of race and ethnicity is critical;
however there still remains unstandardized assessment and challenges to
implementation. The authors highlight specific problems in the assessment of race
and ethnicity in research, such as missing data, misclassification,
classification categories too limited to reflect many peoples' social identities,
and inappropriate aggregation of ethnoracial subgroups. CONCLUSIONS: A proposal
is made for a minimal uniform assessment standard of race and ethnicity.
Additional recommendations incorporate principles proposed by the Institute of
Medicine that allow for more granular assessment of race and ethnicity to better
capture individual identity and cultural factors as they relate to the
assessment, experience and management of PTSD. (PsycINFO Database Record
PMID- 27607767
TI - An Internet-based writing intervention for PTSD in veterans: A feasibility and
pilot effectiveness trial.
AB - [Correction Notice: An Erratum for this article was reported in Vol 9(4) of
Psychological Trauma: Theory, Research, Practice, and Policy (see record 2016
54154-001). In the article, the names of authors Adil Alaoui and Anas Belouali
were misspelled as Adil Aloui and Anas Beloui respectively. All versions of this
article have been corrected.] Objective: Veterans suffering from posttraumatic
stress disorder (PTSD) may avoid or fail to follow through with a full course of
face-to-face mental health treatment for a variety of reasons. We conducted a
pilot effectiveness trial of an online intervention for veterans with current
PTSD to determine the feasibility, safety, and preliminary effectiveness of an
online writing intervention (i.e., Warriors Internet Recovery & EDucation
[WIRED]) as an adjunct to face-to-face psychotherapy. Method: Veterans (N = 34)
who had served in Iraq or Afghanistan with current PTSD subsequent to deployment
related trauma were randomized to Veterans Affairs (VA) mental health treatment
as usual (TAU) or to treatment as usual plus the online intervention (TAU +
WIRED). All research participants were recruited from the Trauma Services
Program, VA Medical Center, Washington, DC. They completed baseline assessments
as well as assessments 12 weeks and 24 weeks after the baseline assessment. The
online intervention consisted of therapist-guided writing, using principles of
prolonged exposure and cognitive therapy. The intervention was adapted from an
evidence-based treatment used in The Netherlands and Germany for individuals who
had been exposed to nonmilitary traumas. Results: In addition to showing that the
online intervention was both feasible to develop and implement, as well as being
safe, the results showed preliminary evidence of the effectiveness of the TAU +
WIRED intervention in this patient population, with particular evidence in
reducing PTSD symptoms of hyperarousal. Conclusion: With minor modifications to
enhance the therapeutic alliance, this intervention should be tested in a larger
clinical trial to determine whether this method of online intervention might
provide another alternative to face-to-face treatment for veterans with PTSD.
(PsycINFO Database Record
PMID- 27607768
TI - Assault-related shame mediates the association between negative social reactions
to disclosure of sexual assault and psychological distress.
AB - OBJECTIVE: Several studies have identified associations between social reactions
to disclosure of sexual assault and psychological distress; however, no studies
have evaluated shame as a mediator of this association. This study evaluated
assault-related shame as a mediator of the associations between negative social
reactions to disclosure of sexual assault and symptoms of posttraumatic stress
disorder (PTSD), depression, and global distress and hypothesized that there
would be an indirect effect of social reactions to disclosure upon symptoms of
psychopathology via assault-related shame. METHOD: Participants were 207 female
psychology undergraduates who reported past history of completed or attempted
sexual assault and had disclosed the assault to at least 1 other person.
Participants completed self-report measures of social reactions to sexual assault
disclosure, assault-related shame, and symptoms of psychopathology. RESULTS:
Participants reported significant histories of attempted or completed sexual
assault and indicated clinically significant symptoms of depression and
subthreshold symptoms of PTSD and global distress, on average. Evaluation of
structural models confirmed the hypothesized indirect effect of negative social
reactions to sexual assault disclosure upon symptoms of PTSD (z = 5.85, p <
.001), depression (z = 4.56, p < .001), and global distress (z = 4.82, p < .001)
via assault-related shame. CONCLUSIONS: These findings offer new insight
concerning the intervening role of assault-related shame and highlight the
importance of shame as a target for therapeutic intervention. This study suggests
the need for future research concerning the role of shame in the etiology of PTSD
and process of disclosure among survivors of attempted or completed sexual
assault. (PsycINFO Database Record
PMID- 27607769
TI - Efficient Reductive Decomposition of Perfluorooctanesulfonate in a High Photon
Flux UV/Sulfite System.
AB - Hydrated electron (eaq-) induced reduction techniques are promising for
decomposing recalcitrant organic pollutants. However, its vigorous reactivity
with copresent scavenging species and the difficulty in minimizing the
competitive reactions make the proportion of eaq- participating in pollutant
decomposition low, reflecting by slow decomposition kinetics. In this study, a
high photon flux UV/sulfite system was employed to promote eaq- production. Its
feasibility in enhancing a notorious recalcitrant pollutant, PFOS, decomposition
was investigated. The effective photon flux utilized for producing eaq- was 9.93
* 10-8 einstein/cm2.s. At initial solution pH 9.2, with DO about 5 mg/L, and at
around 25 degrees C, 98% PFOS was decomposed within 30 min from its initial
concentration of 32 MUM. The kobs of PFOS decomposition was 0.118 min-1 (7.08 h
1), and about 8-400 folds faster than those obtained in other reductive
approaches. In this system, PFOS decomposition showed can tolerate copresent 7 mg
N/L of NO3-. Suggested by molecular orbitals and thermodynamic analyses, the
mechanisms responsible for PFOS decomposition involve defluorination,
desulfonation, and centermost C-C bond scission. By demonstrating a more
practical relevant treatment process, the outcomes of this study would be helpful
for facilitating future applications of eaq- induced reduction techniques for
efficient recalcitrant pollutants decomposition.
PMID- 27607833
TI - Isolation and Characterization of the 2,2'-Azinobis(3-ethylbenzothiazoline-6
sulfonic acid) (ABTS) Radical Cation-Scavenging Reaction Products of Arbutin.
AB - Arbutin, a glucoside of hydroquinone, has shown strong 2,2'-azinobis(3
ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation-scavenging activity,
especially in reaction stoichiometry. This study investigated the reaction
mechanism of arbutin against ABTS radical cation that caused high stoichiometry
of arbutin in an ABTS radical cation-scavenging assay. HPLC analysis of the
reaction mixture of arbutin and ABTS radical cation indicated the existence of
two reaction products. The two reaction products were purified and identified to
be a covalent adduct of arbutin with an ABTS degradation fragment and 3-ethyl-6
sulfonate benzothiazolone. A time-course study of the radical-scavenging
reactions of arbutin and the two reaction products suggested that one molecule of
arbutin scavenges three ABTS radical cation molecules to generate an arbutin-ABTS
fragment adduct as a final reaction product. The results suggest that one
molecule of arbutin reduced two ABTS radical cation molecules to ABTS and then
cleaved the third ABTS radical cation molecule to generate two products, an
arbutin-ABTS fragment adduct and 3-ethyl-6-sulfonate benzothiazolone.
PMID- 27607834
TI - Pharmacophore modeling, 3D-QSAR, and in silico ADME prediction of N-pyridyl and
pyrimidine benzamides as potent antiepileptic agents.
AB - Biological mechanism attributing mutations in KCNQ2/Q3 results in benign familial
neonatal epilepsy (BFNE), a rare form of epilepsy and thus neglected. It offers a
potential target for antiepileptic drug discovery. In the present work, a
pharmacophore-based 3D-QSAR model was generated for a series of N-pyridyl and
pyrimidine benzamides possessing KCNQ2/Q3 opening activity. The pharmacophore
model generated contains one hydrogen bond donor (D), one hydrophobic (H), and
two aromatic rings (R). They are the crucial molecular write-up detailing
predicted binding efficacy of high affinity and low affinity ligands for KCNQ2/Q3
opening activity. Furthermore, it has been validated by using a biological
correlation between pharmacophore hypothesis-based 3D-QSAR variables and
functional fingerprints of openers responsible for the receptor binding and also
by docking of these benzamides into the validated homology model. Excellent
statistical computational tools of QSAR model such as good correlation
coefficient (R2 > 0.80), higher F value (F > 39), and excellent predictive power
(Q2 > 0.7) with low standard deviation (SD <0.3) strongly suggest that the
developed model could be used for prediction of antiepileptic activity of newer
analogs. A preliminary pharmacokinetic profile of these derivatives was also
performed on the basis of QikProp predictions.
PMID- 27607835
TI - Presence of Escherichia coli O157, Salmonella spp., and Listeria monocytogenes in
Raw Ovine Milk Destined for Cheese Production and Evaluation of the Equivalence
Between the Analytical Methods Applied.
AB - Italy is one of the main producers and exporters of cheese made from
unpasteurized sheep milk. Since raw milk and its derived products are known
sources of human infections, cheese produced from raw sheep milk could pose a
microbiological threat to public health. Hence, the objectives of the study were:
to characterize the potential risk of the presence of pathogens Escherichia coli
O157, Listeria monocytogenes, and Salmonella in raw ovine milk destined for
cheese production obtained from all the sheep farms (n = 24) in the Marches
region (Central Italy) that directly transform raw milk into cheeses and to
evaluate the equivalence between the analytical methods applied. A three-step
molecular method (simultaneous culture enrichment, species-specific DNA magnetic
isolation, and multiplex real-time polymerase chain reaction) was used for milk
(n = 143) and cheese (n = 5) analysis over a 3-year period. L. monocytogenes was
not detected on any of the farms, while E. coli O157 was found on three farms,
although only using the molecular method. Four farms tested positive for
Salmonella spp., and Salmonella enterica subsp. diarizonae serovar 61:k:1,5,7 was
isolated in one of those cases. This information highlights the need to develop
preventative measures to guarantee a high level of consumer safety for this
specific product line, and the molecular method could be a time-saving and
sensitive tool to be used in routine diagnosis.
PMID- 27607837
TI - Near-field coupling and resonant cavity modes in plasmonic nanorod metamaterials.
AB - Plasmonic resonant cavities are capable of confining light at the nanoscale,
resulting in both enhanced local electromagnetic fields and lower mode volumes.
However, conventional plasmonic resonant cavities possess large Ohmic losses at
metal-dielectric interfaces. Plasmonic near-field coupling plays a key role in a
design of photonic components based on the resonant cavities because of the
possibility to reduce losses. Here, we study the plasmonic near-field coupling in
the silver nanorod metamaterials treated as resonant nanostructured optical
cavities. Reflectance measurements reveal the existence of multiple resonance
modes of the nanorod metamaterials, which is consistent with our theoretical
analysis. Furthermore, our numerical simulations show that the electric field at
the longitudinal resonances forms standing waves in the nanocavities due to the
near-field coupling between the adjacent nanorods, and a new hybrid mode emerges
due to a coupling between nanorods and a gold-film substrate. We demonstrate that
this coupling can be controlled by changing the gap between the silver nanorod
array and gold substrate.
PMID- 27607836
TI - Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa
Chromosomal Monophyly and Broad Geographic Distribution.
AB - Through full genome analyses of four atypical Bacillus cereus isolates,
designated B. cereus biovar anthracis, we describe a distinct clade within the B.
cereus group that presents with anthrax-like disease, carrying virulence plasmids
similar to those of classic Bacillus anthracis. We have isolated members of this
clade from different mammals (wild chimpanzees, gorillas, an elephant and goats)
in West and Central Africa (Cote d'Ivoire, Cameroon, Central African Republic and
Democratic Republic of Congo). The isolates shared several phenotypic features of
both B. anthracis and B. cereus, but differed amongst each other in motility and
their resistance or sensitivity to penicillin. They all possessed the same
mutation in the regulator gene plcR, different from the one found in B.
anthracis, and in addition, carry genes which enable them to produce a second
capsule composed of hyaluronic acid. Our findings show the existence of a
discrete clade of the B. cereus group capable of causing anthrax-like disease,
found in areas of high biodiversity, which are possibly also the origin of the
worldwide distributed B. anthracis. Establishing the impact of these pathogenic
bacteria on threatened wildlife species will require systematic investigation.
Furthermore, the consumption of wildlife found dead by the local population and
presence in a domestic animal reveal potential sources of exposure to humans.
PMID- 27607838
TI - Synthesis of Cycloparaphenylenes Bearing Furan-2,5-diyl or 2,2'-Bifuran-5,5'-diyl
Units in the Macrocyclic Structures.
AB - Synthetic pathways to furan-containing cycloparaphenylenes (CPPs) as molecular
nanohoops bearing 10, 12, and 15 aromatic units including furan-2,5-diyl or 2,2'
bifuran-5,5'-diyl units have been developed. The X-ray structures of a partially
hydrogenated bifuran-containing CPP precursor and the corresponding fully
aromatized bifuran-containing CPP were obtained to allow the determination of
their conformational arrangements in the crystal lattice. The optical and
electrochemical properties of the furan-containing CPPs were investigated.
PMID- 27607839
TI - Biodegradation-Resistant Multilayers Coated with Gold Nanoparticles. Toward a
Tailor-made Artificial Extracellular Matrix.
AB - Polymer multicomponent coatings such as multilayers mimic an extracellular matrix
(ECM) that attracts significant attention for the use of the multilayers as
functional supports for advanced cell culture and tissue engineering. Herein,
biodegradation and molecular transport in hyaluronan/polylysine multilayers
coated with gold nanoparticles were described. Nanoparticle coating acts as a
semipermeable barrier that governs molecular transport into/from the multilayers
and makes them biodegradation-resistant. Model protein lysozyme (mimics of ECM
soluble signals) diffuses into the multilayers as fast- and slow-diffusing
populations existing in an equilibrium. Such a composite system may have high
potential to be exploited as degradation-resistant drug-delivery platforms
suitable for cell-based applications.
PMID- 27607840
TI - A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines
Using Ammonia Borane.
AB - Inspired by the zwitterion species generated from the splitting of H2 by
frustrated Lewis pairs, we put forward a novel frustrated Lewis pair by the
combination of Hdelta- and Hdelta+ incorporated Lewis acid and base together.
Piers' borane and chiral tert-butylsulfinamide were chosen as the FLP, and a
metal-free asymmetric transfer hydrogenation of imines was realized with high
enantioselectivities. Significantly, with ammonia borane as hydrogen source, a
catalytic asymmetric reaction using 10 mol % of Piers' borane, chiral tert
butylsulfinamide, and pyridine additive, has been successfully achieved to
furnish optically active amines in 78-99% yields with 84-95% ee's. Experimental
and theoretical mechanistic studies reveal an interesting 8-membered ring
hydrogen transfer transition state and an expected regeneration of reactive
species with ammonia borane. Accordingly, a plausible catalytic pathway for this
reaction is depicted.
PMID- 27607843
TI - Knitted Carbon-Nanotube-Sheath/Spandex-Core Elastomeric Yarns for Artificial
Muscles and Strain Sensing.
AB - Highly stretchable, actuatable, electrically conductive knitted textiles based on
Spandex (SPX)/CNT (carbon nanotube) composite yarns were prepared by an
integrated knitting procedure. SPX filaments were continuously wrapped with CNT
aerogel sheets and supplied directly to an interlocking circular knitting machine
to form the three-dimensional electrically conductive and stretchable textiles.
By adjusting the SPX/CNT feed ratio, the fabric electrical conductivities could
be tailored in the range of 870 to 7092 S/m. The electrical conductivity depended
on tensile strain, with a linear and largely hysteresis-free resistance change
occurring on loading and unloading between 0 and 80% strain. Electrothermal
heating of the stretched fabric caused large tensile contractions of up to 33%,
and generated a gravimetric mechanical work capacity during contraction of up to
0.64 kJ/kg and a maximum specific power output of 1.28 kW/kg, which far exceeds
that of mammalian skeletal muscle. The knitted textile provides the combination
of strain sensing and the ability to control dimensions required for smart
clothing that simultaneously monitors the wearer's movements and adjusts the
garment fit or exerts forces or pressures on the wearer, according to needs. The
developed processing method is scalable for the fabrication of industrial
quantities of strain sensing and actuating smart textiles.
PMID- 27607841
TI - Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a
Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for
Hormone-Responsive Human Breast Cancer.
AB - The aim of this study is based on the evaluation of anticancer, anti-inflammatory
activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin
tested alone and in combination to a macrolide derivative of rapamycin RAD001
(everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological
investigations were focused on the receptor mediated cellular internalization of
the nanohydrogel and its abilities to reduce secretion of several cytokines (IL
8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory
conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time
dependent cytoplasmatic accumulation with abilities to reduce secretion of all
cytokines of ~60% compared to untreated cells. Combination of formulated
quercetin and everolimus leads to a synergistic cytotoxic effects with a
Combination Index of 0.38. These results highlights the importance of synergistic
effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the
regulation of human breast cancer cell proliferation and emphasize the antitumor
and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063
2074, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27607842
TI - Environmental Instability and Degradation of Single- and Few-Layer WTe2
Nanosheets in Ambient Conditions.
AB - The ambient environmental instability and degradation mechanism of single- and
few-layer WTe2 are investigated. Oxidation of W and Te atoms appears to be a main
reason for degradation. Single-layer samples' Raman signals disappear within 20
min in air. Few-layer WTe2 exhibits saturating degradation behavior: only the top
layer WTe2 is oxidized; the degraded layer can protect inner layers from further
degradation.
PMID- 27607844
TI - Ethnic differences in the levator hiatus and pelvic organ descent: a prospective
observational study.
AB - OBJECTIVE: To date, most studies on functional anatomy of the pelvic floor have
focused on Caucasian women. There is scant information on this topic involving
other ethnic groups. The aim of this study was to investigate levator hiatal area
and pelvic organ descent in three racially diverse ethnic groups of healthy
nulliparous South Asian, Caucasian and black South African women, using
three/four-dimensional (3D/4D) transperineal ultrasound (TPS). METHODS:
Nulliparous women aged 18-40 years from three different ethnic groups were
recruited for this prospective observational study between June 2012 and April
2015. After informed consent and clinical examination of the pelvic floor, all
patients underwent a 3D/4D-TPS examination. Ultrasound volumes were captured at
rest, on maximum pelvic floor muscle contraction (PFMC) and on maximal Valsalva
maneuver. Analyses of variance and covariance were performed to compare the three
ethnic groups, and a post-hoc Bonferroni pairwise test was applied. RESULTS: A
total of 207 nulliparous women were recruited, comprising 41 South Asian, 69
Caucasian and 97 black women. After controlling for age and body mass index, all
measurements of mean levator hiatal area at rest, on PFMC and on Valsalva were
higher in black women (all P < 0.0001). Post-hoc Bonferroni pairwise comparison
revealed that black women had greater pelvic organ descent and levator hiatal
area compared with South Asian and Caucasian women (P < 0.0001). CONCLUSION: This
comparative study indicates that there are significant differences in levator
hiatal area and pelvic organ mobility between Caucasian, South Asian and black
ethnic groups. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27607845
TI - Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and
Extend Lifespan in Caenorhabditis elegans.
AB - Tenebrio molitor are large insects and their larvae are consumed as food in many
countries. The nutritional composition of T. molitor has been studied and
contains high amounts of proteins, unsaturated fatty acids, and valuable
minerals. However, the bioactivity of T. molitor has not been fully understood.
We examined the effects of T. molitor extracts on resistance to oxidative stress
and organism's lifespan using Caenorhabditis elegans as a model system. The
response to heat shock and ultraviolet (UV) irradiation was monitored in vivo.
The extracts from T. molitor showed significant effects on resistance to
oxidative stress and UV irradiation and extend both mean and maximum lifespan of
C. elegans. The number of progeny produced significantly increased in animals
supplemented with T. molitor extracts. In addition, the expression of hsp-16.2
and sod-3 was markedly upregulated by supplementation with T. molitor extracts.
These findings suggest that T. molitor extracts can increase response to
stressors and extend lifespan by the induction of longevity assurance genes in C.
elegans.
PMID- 27607846
TI - Role of progranulin in the regulation of vascular tone: (patho)physiological
implications.
PMID- 27607847
TI - Effect of a Nurse-Managed Telemetry Discontinuation Protocol on Monitoring
Duration, Alarm Frequency, and Adverse Patient Events.
AB - Telemetry monitoring is a limited resource. This quality improvement project
describes a nurse-managed telemetry discontinuation protocol aimed at stopping
telemetry monitoring when it is no longer indicated. After implementing the
protocol, data were collected for 6 months and compared with a preintervention
time frame. There was a mean decrease in telemetry monitor usage and a decreased
likelihood of remaining on a telemetry monitor until discharge. A nurse-managed
telemetry discontinuation protocol was effective in decreasing overmonitoring and
ensuring telemetry availability.
PMID- 27607848
TI - Initiation of a Transitions Program: "Two Million Melvins".
PMID- 27607849
TI - Nurses' Perceived Skills and Attitudes About Updated Safety Concepts: Impact on
Medication Administration Errors and Practices.
AB - Approximately a quarter of medication errors in the hospital occur at the
administration phase, which is solely under the purview of the bedside nurse. The
purpose of this study was to assess bedside nurses' perceived skills and
attitudes about updated safety concepts and examine their impact on medication
administration errors and adherence to safe medication administration practices.
Findings support the premise that medication administration errors result from an
interplay among system-, unit-, and nurse-level factors.
PMID- 27607851
TI - A Critical Qualitative Study of the Position of Middle Managers in Health Care
Quality Improvement.
AB - To date, health care quality improvement (QI) has focused on the engagement of
executive leadership and frontline staff as key factors for success. Little work
has been done on understanding how mid-level unit/program managers perceive their
role in QI and how capacity could be built at this level to increase success. We
present ethnographic data on the experience of hospital middle managers to
consider how the expectations and capacity of their current position might
influence QI progress organizationally.
PMID- 27607850
TI - Feasibility Study of Interventions to Reduce Medication Omissions Without
Documentation: Recall and Check Study.
AB - We conducted a feasibility study to test an intervention to reduce medication
omissions without documentation using nurse-initiated recall cards and medication
chart checking at handover. No significant difference in the omission rate per
100 medications was found, although after adjusting for hospital and patient age,
a significant effect occurred in the intervention group (n = 262 patients)
compared with the control group (n = 272). This intervention may reduce
medication omissions without documentation, requiring further study within larger
samples.
PMID- 27607852
TI - Sexual Health in Women Affected by Cancer: Focus on Sexual Pain.
AB - As cancer therapies improve, the number of women surviving or living long lives
with cancer continues to increase. Treatment modalities, including surgery,
chemotherapy, radiotherapy, and hormonal therapy, affect sexual function and may
cause sexual pain through a variety of mechanisms, depending on treatment type.
Adverse sexual effects resulting from ovarian damage, anatomic alterations, and
neurologic, myofascial, or pelvic organ injury may affect more than half of women
affected by cancer. Despite the fact that no specialty is better qualified to
render care for this consequence of cancer treatments, many obstetrician
gynecologists (ob-gyns) feel uncomfortable or ill-equipped to address sexual pain
in women affected by cancer. Asking about sexual pain and dyspareunia and
performing a thorough physical examination are essential steps to guide
management, which must be tailored to individual patient goals. Understanding the
cancer treatment-related pathophysiology of sexual pain aids in providing this
care. Effective mechanism-based treatments for sexual pain and dyspareunia are
available, and by using them, knowledgeable ob-gyns can enhance the quality of
life of potentially millions of women affected by cancer.
PMID- 27607853
TI - Pharmacologic Thromboprophylaxis in Obstetrics: Broader Use Demands Better Data.
PMID- 27607854
TI - Stress at Birth and Its Inextricable Link to the Neonatal Transition.
PMID- 27607855
TI - Connect the Dots-October 2016.
PMID- 27607856
TI - What Is New in Endometrial Cancer?: Best Articles From the Past Year.
AB - This month we focus on current research in endometrial cancer. Dr. Wright
discusses four recent publications, which are concluded with a "bottom line" that
is the take-home message. The complete reference for each can be found in on this
page, along with direct links to the abstracts.
PMID- 27607857
TI - National Partnership for Maternal Safety: Consensus Bundle on Venous
Thromboembolism.
AB - Obstetric venous thromboembolism is a leading cause of severe maternal morbidity
and mortality. Maternal death from thromboembolism is amenable to prevention, and
thromboprophylaxis is the most readily implementable means of systematically
reducing the maternal death rate. Observational data support the benefit of risk
factor-based prophylaxis in reducing obstetric thromboembolism. This bundle,
developed by a multidisciplinary working group and published by the National
Partnership for Maternal Safety under the guidance of the Council on Patient
Safety in Women's Health Care, supports routine thromboembolism risk assessment
for obstetric patients, with appropriate use of pharmacologic and mechanical
thromboprophylaxis. Safety bundles outline critical clinical practices that
should be implemented in every maternity unit. The safety bundle is organized
into four domains: Readiness, Recognition, Response, and Reporting and Systems
Learning. Although the bundle components may be adapted to meet the resources
available in individual facilities, standardization within an institution is
strongly encouraged.
PMID- 27607858
TI - Burch Retropubic Urethropexy Compared With Midurethral Sling With Concurrent
Sacrocolpopexy: A Randomized Controlled Trial.
AB - OBJECTIVE: To compare efficacy and safety of retropubic Burch urethropexy and a
midurethral sling in women with stress urinary incontinence (SUI) undergoing
concomitant pelvic floor repair with sacrocolpopexy. METHODS: Women were randomly
assigned to Burch retropubic urethropexy (n=56) or retropubic midurethral sling
(n=57) through dynamic allocation balancing age, body mass index, history of
prior incontinence surgery, intrinsic sphincter deficiency, preoperative
incontinence diagnosis, and prolapse stage. Overall and stress-specific
continence primary outcomes were ascertained with validated questionnaires and a
blinded cough stress test. RESULTS: Enrollment was June 1, 2009, through August
31, 2013. At 6 months, no difference was found in overall (29 midurethral sling
[51%] compared with 23 Burch [41%]; P=.30) (odds ratio [OR] 1.49, 95% confidence
interval [CI] 0.71-3.13) or stress-specific continence rates (42 midurethral
sling [74%] compared with 32 Burch [57%]; P=.06) (OR 2.10, 95% CI 0.95-4.64)
between groups. However, the midurethral sling group reported greater
satisfaction (78% compared with 57%; P=.04) and were more likely to report
successful surgery for SUI (71% compared with 50%; P=.04) and to resolve pre
existing urgency incontinence (72% compared with 41%; P=.03). No difference was
found in patient global impression of severity or symptom improvement,
complication rates, or mesh exposures. CONCLUSION: There was no difference in
overall or stress-specific continence rates between midurethral sling and Burch
urethropexy groups at 6 months. However, the midurethral sling group reported
better patient-centered secondary outcomes.
PMID- 27607859
TI - Effects of Depot Medroxyprogesterone Acetate Injection Timing on Medical Abortion
Efficacy and Repeat Pregnancy: A Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the effects of timing of depot medroxyprogesterone acetate
injection on medical abortion outcome and risk of repeat pregnancy within the
subsequent 6 months. METHODS: In a multinational randomized trial, we assigned
women undergoing medical abortion who wanted depot medroxyprogesterone acetate to
administration either with mifepristone (Quickstart group) or after the abortion
(Afterstart group). We ascertained abortion outcome, pregnancies, and
contraception use over 7 months. RESULTS: From August 2013 to March 2015, we
enrolled 461 participants with pregnancy durations of 75 days or less. Of
participants included in the abortion outcome analyses, 14 of 220 (6.4%) and 12
of 226 (5.3%) in the Quickstart and Afterstart groups, respectively, had surgery
to complete the abortion; the upper 90% confidence limit on this difference was
4.9%, within our prestipulated 5% noninferiority margin. Ongoing pregnancy after
initial abortion treatment was significantly more common in the Quickstart group
(8/220 [3.6%]) than in the Afterstart group (2/226 [0.9%]); the difference was
2.7% (90% confidence interval 0.4-5.6%). By 6 months, 5 of 213 (2.3%) and 7 of
217 (3.2%) in the Quickstart and Afterstart groups, respectively, became pregnant
(exact log-rank test, P=.64). Use of highly effective contraceptives was
significantly more common in the Quickstart group at 31 days (P<.001), but no
difference was apparent at 6 months. The Quickstart group was significantly more
satisfied with group assignment. CONCLUSION: Depot medroxyprogesterone acetate
administration with mifepristone did not appreciably increase the risk of surgery
after medical abortion but did increase the risk of ongoing pregnancy. It
enhanced patient satisfaction, but we found no evidence that it decreased 6-month
risk of repeat pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
https://clinicaltrials.gov, NCT01902485.
PMID- 27607860
TI - Alternative Colposcopy Techniques: A Systematic Review and Meta-analysis.
AB - OBJECTIVE: To assess the diagnostic value of alternative (digital) colposcopy
techniques for detection of cervical intraepithelial neoplasia (CIN) 2 or worse
in a colposcopy population. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov,
and the Cochrane Library were searched from inception up to January 11, 2016, for
studies that evaluated the diagnostic value of alternative (digital) colposcopy
techniques. METHODS OF STUDY SELECTION: Inclusion criteria were: 1) an
alternative (digital) colposcopy technique was used in a colposcopy population;
2) a histologic outcome was reported, classified as CIN, differentiating between
mild dysplasia or less (CIN 1 or less), and moderate dysplasia or worse (CIN 2 or
greater); 3) the entire cervix was scanned at once or a per-woman analysis was
performed; 4) no other topical application than acetic acid and Lugol's solution
was used; 5) at least three eligible studies had to be available within a single
technique; and 6) studies obtained research ethics approval. Language was
restricted to English. TABULATION, INTEGRATION, AND RESULTS: Two reviewers
assessed the eligibility of the identified articles. Disagreements were resolved
by a third reviewer. Thirteen studies met the inclusion criteria. We found six
studies on fluorescence and reflectance spectroscopy, including 2,530 women, with
a pooled sensitivity of 93% (95% confidence interval [CI] 89-95%) and specificity
of 62% (95% CI 47-76%). Four studies on dynamic spectral imaging were found
including 1,173 women with a pooled sensitivity of 69% (95% CI 48-85%) and
specificity of 83% (95% CI 76-88%). We found three studies on optical coherence
tomography including 693 women with a pooled sensitivity of 48% (95% CI 32-64%)
and specificity of 77% (95% CI 52-91%). Previously published conventional
colposcopy results showed a sensitivity of 61% (95% CI 58-63%) and a specificity
of 85% (95% CI 83-86%). CONCLUSION: Alternative (digital) colposcopy techniques
may result in increased sensitivity and specificity, but no recommendation for
introduction in clinical practice can be made yet.
PMID- 27607861
TI - Fetal Release of Copeptin in Response to Maternal Oxytocin Administration: A
Randomized Controlled Trial.
AB - OBJECTIVE: To test whether an oxytocin challenge test raises neonatal levels of
copeptin, the C-terminal portion of proarginine vasopressin, a sensitive stress
marker elevated in neonates born by vaginal delivery as opposed to elective
cesarean delivery. METHODS: In a randomized controlled trial in women with a
singleton pregnancy undergoing elective cesarean delivery at greater than 36
weeks of gestation and no contractions or rupture of membranes, we compared
arterial umbilical cord plasma concentrations of copeptin between neonates
exposed to an oxytocin challenge test before elective cesarean delivery and those
administered saline infusion (placebo group). Women randomized to an oxytocin
challenge test received 5 international units/500 mL oxytocin Ringer lactate
infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three
uterine contractions per 10-minute interval, at which point it was discontinued.
Neonatal copeptin levels were the primary endpoint. Secondary endpoints included
biochemical and physiologic parameters of fetal and maternal well-being. RESULTS:
From January 2012 to October 2012 and from September 2013 to January 2015, 78
women underwent an oxytocin challenge test and 78 placebo infusion, of whom 12
and 11, respectively, were excluded as a result of insufficient blood sample
volume for analysis. Umbilical cord plasma copeptin levels [median (range)] were
higher in neonates who underwent an oxytocin challenge test than those who
underwent placebo infusion: 22.2 (3.22-2,319) compared with 7.39 (2.5-344.6)
pmol/L (P<.001). There were no statistically significant differences between the
two groups in secondary outcomes. CONCLUSION: Oxytocin challenge test-induced
contractions before elective cesarean delivery trigger fetal copeptin release.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov,
NCT01962701.
PMID- 27607862
TI - Maternal Death Due to Clostridium novyi in an Injection Drug User.
AB - BACKGROUND: Soft-tissue infections in women with subcutaneous injection drug use
are often polymicrobial. CASE: A 21-year-old nulliparous woman presented at 14-15
weeks of gestation with several gluteal abscesses related to subcutaneous
injection of heroin. She was well appearing, afebrile, and without findings of
systemic illness. After empiric broad-spectrum intravenous antibiotics, same-day
incision and drainage was performed. Immediately after the procedure, she
developed refractory hypotension, severe tachycardia, pulmonary edema, and
leukemoid reaction (white blood cell count 80*10/L). Cardiac arrest ensued, and
she died within 4 hours of onset of sepsis and within 24 hours of presentation.
Wound cultures identified Clostridium novyi. CONCLUSION: Local, soft-tissue
infections that includes C novyi can result in rapidly fatal, toxin-mediated
septic shock in pregnant women with high-risk social behavior.
PMID- 27607863
TI - Spontaneous Twin Pregnancy After Oophoropexy and Pelvic Radiation for Rectal
Cancer.
AB - BACKGROUND: Pregnancy after adulthood pelvic radiation is rare. There is a
paucity of literature to guide preconception counseling and pregnancy management
for these patients. CASE: A 36-year-old woman, gravida 2 para 1001, was referred
at 28 weeks of gestation with spontaneous twins, preterm premature rupture of
membranes, and a history of rectal cancer that had been treated 3 years
previously with oophoropexy, chemoradiation, and abdominal perineal resection.
Delivery was complicated by difficult fetal extraction and resulted in the demise
of twin A. CONCLUSION: Pregnancy after adulthood pelvic radiation is a
potentially morbid event. Patients should be counseled about the potential
delivery complications as well as the need for contraception after oophoropexy
with intact fallopian tubes.
PMID- 27607864
TI - Active Management of the Third Stage of Labor With a Combination of Oxytocin and
Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered
simultaneously with oxytocin as part of the active management of the third stage
of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled
trial recruited women in the first stage of labor with expected vaginal
deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple
pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants
received routine intravenous oxytocin and were randomly allocated to receive 400
micrograms misoprostol or placebo orally immediately after delivery of the
newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within
2 hours of birth). Secondary outcomes included severe postpartum hemorrhage
(1,000 mL or greater) and adverse maternal events such as fever, shivering, and
nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of
postpartum hemorrhage according to a two-tailed alpha at 0.05 with 80% power. An
interim analysis was planned after 50% enrollment. RESULTS: Participant
enrollment occurred from April 2010 to September 2013. Baseline characteristics
were similar in the two groups. The study was discontinued after the planned
interim analysis including 1,721 patients showed that misoprostol was not
effective and was associated with significantly more adverse effects. The rate of
postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in
the placebo group (P=.98), and rates of severe postpartum hemorrhage were 1.8%
and 2.4%, respectively (P=.57). Maternal adverse events occurred significantly
more frequently in the misoprostol group (for fever 30.4% in the misoprostol
group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the
misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION:
Misoprostol administered with prophylactic routine oxytocin did not reduce the
rate of postpartum hemorrhage risk and increased the rate of adverse events.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov,
NCT01113229.
PMID- 27607865
TI - Perinatal Outcomes in Cephalic Compared With Noncephalic Singleton Presentation
in the Setting of Preterm Premature Rupture of Membranes Before 32 Weeks of
Gestation.
AB - OBJECTIVE: To investigate the relationship between fetal presentation at the time
of admission for preterm premature rupture of membranes (PROM) and perinatal
outcomes, including gestational latency, among women in a large and well
characterized population with preterm PROM at less than 32 weeks of gestation.
METHODS: This was a secondary analysis of data from women randomized to receive
magnesium sulfate compared with placebo in the previously reported Maternal-Fetal
Medicine Units Network Beneficial Effects of Antenatal Magnesium Sulfate (1997
2004) trial. Women with a singleton gestation and preterm PROM were included.
Fetal presentation at the time of randomization was recorded. Associations of
fetal position (cephalic compared with noncephalic) with perinatal outcomes were
compared using chi, Fisher exact, and Wilcoxon rank-sum tests. Perinatal outcomes
included gestational latency, abruption, and neonatal morbidity and mortality.
Multivariable regression (logistic, linear, and Cox) analyses were used to adjust
for potential confounding factors. RESULTS: Of the 1,767 eligible women, 439
(24.5%) had a noncephalic presentation. Noncephalic presentation was associated
with an earlier median gestational age at the time of preterm PROM (26.6 compared
with 28.4 weeks of gestation, P<.001), but no difference in gestational latency
(7.5 compared with 7.7 days, P=.7, adjusted hazard ratio 1.09, 95% confidence
interval [CI] 0.97-1.23). There were no differences in odds of abruption or
neonatal morbidity in multivariable analyses. However, even after controlling for
potential confounding factors including gestational age at delivery and mode of
delivery, odds of neonatal death before discharge was greater for noncephalic
gestations (11.5% compared with 3.4%, P<.001; adjusted odds ratio 2.24, 95% CI
1.12-4.48). CONCLUSION: Even after controlling for gestational age and route of
delivery, noncephalic fetuses in the setting of preterm PROM are at greater risk
of neonatal death.
PMID- 27607866
TI - Gynecologic Outcomes After Hysteroscopic and Laparoscopic Sterilization
Procedures.
AB - OBJECTIVE: To compare rates of gynecologic morbidity after laparoscopic and
hysteroscopic sterilization. METHODS: This retrospective cohort study used a
commercial claims administrative database, 2007-2013, to compare rates of
pregnancy, menstrual dysfunction, pelvic pain, hysteroscopic surgery, and intra
abdominal gynecologic surgery after laparoscopic and hysteroscopic sterilization.
Women with 12 or more continuous months of data before and after their index
procedure were included. Pregnancy rates after laparoscopic and hysteroscopic
sterilization were compared for the entire population of women who underwent
hysteroscopic sterilization and the subset who had completed postprocedure
hysterosalpingograms. Cox proportional hazard models were calculated controlling
for age, comorbidities, U.S. geographic region, metropolitan statistical area
designation, and insurance type. RESULTS: A total of 42,391 women underwent
laparoscopic and 27,724 underwent hysteroscopic sterilization. The pregnancy rate
was higher after hysteroscopic than laparoscopic sterilization (adjusted hazard
ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33; 2.4% compared with 2.0%
risk of pregnancy at 2 years). Only 66.1% (n=18,318) of women who underwent
hysteroscopic sterilization received a hysterosalpingogram. This group had
similar pregnancy rates as those who underwent laparoscopic sterilization
(adjusted HR 0.90, 95% CI 0.80-1.02; 1.8% compared with 2.0% at 2 years). After
undergoing hysteroscopic sterilization, more women were diagnosed with menstrual
dysfunction (adjusted HR 1.23, 95% CI 1.20-1.27; 26.8% compared with 22.3% at 2
years), and more women underwent hysteroscopic surgeries (adjusted HR 2.05, 95%
CI 1.96-2.14; 13.8% compared with 6.4% at 2 years), but fewer women were
diagnosed with pelvic pain (adjusted HR 0.83, P<.001; 21.0% compared with 25.6%
at 2 years) and fewer women underwent intra-abdominal gynecologic surgeries
(adjusted HR 0.95, 95% CI 0.90-0.99; 7.7% compared with 8.1% at 2 years),
including hysterectomy (adjusted HR 0.65, 95% CI 0.61-0.69; 10.9% compared with
14.3% at 5 years). CONCLUSION: Hysteroscopic sterilization may be associated with
a higher rate of pregnancy, more menstrual dysfunction, more hysteroscopic
surgeries, less pelvic pain, and fewer intra-abdominal gynecologic surgeries than
laparoscopic sterilization. Pregnancy rates appear to be similar for women who
completed their postprocedure hysterosalpingogram, but only 66% of women did so.
PMID- 27607867
TI - Levonorgestrel Intrauterine Device as an Endometrial Cancer Prevention Strategy
in Obese Women: A Cost-Effectiveness Analysis.
AB - OBJECTIVE: To estimate the cost-effectiveness of the levonorgestrel intrauterine
device (IUD) as an endometrial cancer prevention strategy in obese women.
METHODS: A modified Markov model was used to compare IUD placement at age 50 with
usual care among women with a body mass index (BMI, kg/m) 40 or greater or BMI 30
or greater. The effects of obesity on incidence and survival were incorporated.
The IUD was assumed to confer a 50% reduction in cancer incidence over 5 years.
Costs of IUD and cancer care were included. Clinical outcomes were cancer
diagnosis and deaths from cancer. Incremental cost-effectiveness ratios were
calculated in 2015 U.S. dollars per year of life saved. One-way and two-way
sensitivity analyses and Monte Carlo probabilistic analyses were performed.
RESULTS: For a 50 year old with BMI 40 or greater, the IUD strategy is costlier
and more effective than usual care with an incremental cost-effectiveness ratio
of $74,707 per year of life saved. If the protective effect of the levonorgestrel
IUD is assumed to be 10 years, the incremental cost-effectiveness ratio decreases
to $37,858 per year of life saved. In sensitivity analysis, a levonorgestrel IUD
that reduces cancer incidence by at least 68% in women with BMIs of 40 or greater
or costs less than $500 is potentially cost-effective. For BMI 30 or greater, the
incremental cost-effectiveness ratio of IUD strategy is $137,223 per year of life
saved compared with usual care. In Monte Carlo analysis, IUD placement for BMI 40
or greater is cost-effective in 50% of simulations at a willingness-to-pay
threshold of $100,000 per year of life saved. CONCLUSION: The levonorgestrel IUD
is a potentially cost-effective strategy for prevention of deaths from
endometrial cancer in obese women.
PMID- 27607868
TI - Timing of and Reasons for Unplanned 30-Day Readmission After Hysterectomy for
Benign Disease.
AB - OBJECTIVE: To characterize timing and reasons associated with unplanned 30-day
readmissions after hysterectomy for benign indications. METHODS: We performed a
retrospective analysis of the American College of Surgeons National Surgical
Quality Improvement Project database files from 2012 to 2013. We identified
patterns of 30-day readmission after benign hysterectomy for all surgical
approaches (abdominal, laparoscopic, vaginal). Readmission timing was determined
from discharge date and readmission diagnoses were tabulated. Statistical
analyses included chi tests and multivariable logistic regression. RESULTS: The
30-day readmission rate was 2.8% (1,118/40,580 hysterectomies). Readmissions
complicated 3.7% (361/9,869) of abdominal, 2.6% (576/22,266) of laparoscopic, and
2.1% (181/8,445) of vaginal hysterectomies. Readmissions were more likely when
hysterectomy was performed abdominally (adjusted odds ratio [OR] 1.45, 95%
confidence interval [CI] 1.2-1.76) but not laparoscopically (adjusted OR 1.1, 95%
CI 0.9-1.4) compared with a vaginal approach. Eighty-two percent of readmissions
occurred within 15 days of discharge. The shortest median time to readmission was
associated with pain (3 days), and the longest was associated with noninfectious
wound complications (10 days). Surgical site infection was the most common
diagnosis (abdominal 36.6%, laparoscopic 28.3%, vaginal 32.6%). Surgical site
infections, surgical injuries, and wound complications combined accounted for
51.5% of abdominal, 51.9% of laparoscopic, and 50.8% of vaginal hysterectomy
readmissions. Medical complications such as cardiovascular events and venous
thromboembolism were responsible for 5.8% of abdominal, 6.9% of laparoscopic, and
8.8% of vaginal hysterectomy readmissions. Surgical injuries were responsible for
more readmissions after laparoscopic (unadjusted OR 2.3, 95% CI 1.48-3.65) and
vaginal hysterectomies (unadjusted OR 2.3, 95% CI 1.29-3.97) than abdominal
cases. CONCLUSION: Readmissions after hysterectomy tend to occur shortly after
discharge. Most readmissions are related to surgical issues, most commonly
surgical site infection. Medical complications, including venous thromboembolism,
account for less than 10% of readmissions. Readmission reduction efforts should
focus on early postdischarge follow-up, preventing infectious complications, and
determining preventability of surgical-related reasons for readmission.
PMID- 27607869
TI - Evolving Paradigms in Research and Care in Ovarian Cancers.
AB - The National Academies of Sciences, Engineering, and Medicine convened an expert
committee to examine and summarize the state of the science in ovarian cancer
research. An Executive Summary of the recently released report describing the key
findings and specific recommendations to reduce the incidence of and morbidity
and mortality from ovarian cancers is presented. Highlights include the
recognition that ovarian cancer is not just one disease, but rather a
constellation of distinct cancer types, some of which originate outside of the
ovary. Furthermore, it was noted that our incomplete understanding of the basic
biology of each subtype of ovarian cancer is an impediment to advances in
prevention, screening, early detection, diagnosis, treatment, and supportive
care.
PMID- 27607870
TI - Health Care Disparity and State-Specific Pregnancy-Related Mortality in the
United States, 2005-2014.
AB - OBJECTIVE: To investigate factors associated with differential state maternal
mortality ratios and to quantitate the contribution of various demographic
factors to such variation. METHODS: In a population-level analysis study, we
analyzed data from the Centers for Disease Control and Prevention National Center
for Health Statistics database and the Detailed Mortality Underlying Cause of
Death database (CDC WONDER) that contains mortality and population counts for all
U.S. counties. Bivariate correlations between maternal mortality ratio and all
maternal demographic, lifestyle, health, and medical service utilization
characteristics were calculated. We performed a maximum likelihood factor
analysis with varimax rotation retaining variables that were significant (P<.05)
in the univariate analysis to deal with multicollinearity among the existing
variables. RESULTS: The United States has experienced a continued increase in
maternal mortality ratio since 2007 with rates of 21-22 per 100,000 live births
in 2013 and 2014. This increase in mortality was most dramatic in non-Hispanic
black women. There was a significant correlation between state mortality ranking
and the percentage of non-Hispanic black women in the delivery population.
Cesarean deliveries, unintended births, unmarried status, percentage of non
Hispanic black deliveries, and four or less prenatal visits were significantly
(P<.05) associated with increased maternal mortality ratio. CONCLUSION:
Interstate differences in maternal mortality ratios largely reflect a different
proportion of non-Hispanic black or unmarried patients with unplanned
pregnancies. Racial disparities in health care availability, access, or
utilization by underserved populations are an important issue faced by states in
seeking to decrease maternal mortality.
PMID- 27607872
TI - Distance From Cervicovaginal Junction to Anterior Peritoneal Reflection Measured
During Vaginal Hysterectomy.
AB - OBJECTIVE: To quantify the distance of the dissection plane from the
cervicovaginal junction to the anterior peritoneal reflection for vaginal
hysterectomy. METHODS: This is a descriptive study examining the dissection plane
for anterior colpotomy in 22 surgical patients undergoing vaginal hysterectomy
and in nine cadaver specimens. Intraoperatively, the distance from the vaginal
incision to the anterior peritoneal reflection was measured on the uterus after
removal. In nine of these patients, this distance was also measured before
anterior peritoneal incision. Embalmed cadavers with intact pelvic viscera were
dissected and the distance of the same dissection plane was measured. RESULTS:
Median (interquartile range) surgical patient age was 51.5 (42-63) years and the
main surgical indications were abnormal uterine bleeding and pelvic organ
prolapse. In these patients, the median (interquartile range) distance from
cervicovaginal incision to anterior peritoneal reflection was 3.4 (2.6-3.7) cm.
In cadavers, the median (interquartile range) age was 81 (72-86) years with a
measured distance of 2.7 (2.4-2.9) cm. CONCLUSION: When performing a vaginal
hysterectomy, surgeons can expect a median (range) dissection distance of 3.4
(1.8-4.6) cm from initial incision to the peritoneal reflection for anterior
colpotomy.
PMID- 27607871
TI - Utilization and Outcomes of Sentinel Lymph Node Biopsy for Vulvar Cancer.
AB - OBJECTIVE: To examine the use and predictors of sentinel node biopsy in women
with vulvar cancer. METHODS: The Perspective database, an all-payer database that
collects data from more than 500 hospitals, was used to perform a retrospective
cohort study of women with vulvar cancer who underwent vulvectomy and lymph node
assessment from 2006 to 2015. Multivariable models were used to determine factors
associated with sentinel node biopsy. Length of stay and cost were compared
between women who underwent sentinel node biopsy and lymphadenectomy. RESULTS:
Among 2,273 women, sentinel node biopsy was utilized in 618 (27.2%) and 1,655
(72.8%) underwent inguinofemoral lymphadenectomy. Performance of sentinel node
biopsy increased from 17.0% (95% confidence interval [CI] 12.0-22.0%) in 2006 to
39.1% (95% CI 27.1-51.0%) in 2015. In a multivariable model, women treated more
recently were more likely to have undergone sentinel node biopsy, whereas women
with more comorbidities and those treated at rural hospitals were less likely to
have undergone the procedure. The median length of stay was shorter for those
undergoing sentinel node biopsy (median 2 days, interquartile range 1-3) compared
with women who underwent inguinofemoral lymphadenectomy (median 3 days,
interquartile range 2-4). The cost of sentinel node biopsy was $7,599
(interquartile range $5,739-9,922) compared with $8,095 (interquartile range
$5,917-11,281) for lymphadenectomy. CONCLUSION: The use of sentinel node biopsy
for vulvar cancer has more than doubled since 2006. Sentinel lymph node biopsy is
associated with a shorter hospital stay and decreased cost compared with
inguinofemoral lymphadenectomy.
PMID- 27607873
TI - Ovarian Conservation and Overall Survival in Young Women With Early-Stage Low
Grade Endometrial Cancer.
AB - OBJECTIVE: To characterize contributing factors for ovarian conservation during
surgical treatment for endometrial cancer and to examine the association of
ovarian conservation on survival of young women with early-stage, low-grade
tumors. METHODS: This was a population-based study using the Surveillance,
Epidemiology, and End Results program to identify surgically treated stage I type
I (grade 1-2 endometrioid histology) endometrial cancer cases diagnosed between
1983 and 2012 (N=86,005). Multivariable models were used to identify independent
factors for ovarian conservation. Survival outcomes and cause of death were
examined for women aged younger than 50 with stage I type I endometrial cancer
who underwent ovarian conservation (1,242 among 12,860 women [9.7%]). RESULTS: On
multivariable analysis, age younger than 50 years, grade 1 endometrioid
histology, and tumor size 2.0 cm or less were noted to be independent factors for
ovarian conservation (all, P<.001). For 9,110 women aged younger than 50 years
with stage I grade 1 tumors, cause-specific survival was similar between ovarian
conservation and oophorectomy cases (20-year rates 98.9% compared with 97.7%,
P=.31), whereas overall survival was significantly higher in ovarian conservation
cases than oophorectomy cases (88.8% compared with 82.0%, P=.011). On
multivariable analysis, ovarian conservation remained an independent prognostic
factor for improved overall survival (adjusted hazard ratio 0.73, 95% confidence
interval [CI] 0.54-0.98, P=.036) and was independently associated with a lower
cumulative risk of death resulting from cardiovascular disease compared with
oophorectomy (20-year rates, 2.3% compared with 3.7%, adjusted hazard ratio 0.40,
95% CI 0.17-0.91, P=.029). Contrary, cause-specific survival (20-year rates 94.6%
compared with 96.1%, P=.68) and overall survival (81.0% compared with 80.6%,
P=.91) were similar between ovarian conservation and oophorectomy among 3,750
women aged younger than 50 years with stage I grade 2 tumors. CONCLUSION: Ovarian
conservation is performed in less than 10% of young women with stage I type I
endometrial cancer. Ovarian conservation is associated with decreased mortality
in young women with stage I grade 1 tumors.
PMID- 27607874
TI - Differences in Mortality Between Pregnant and Nonpregnant Women After
Cardiopulmonary Resuscitation.
AB - OBJECTIVE: To examine the association between pregnancy status and in-hospital
mortality after cardiopulmonary resuscitation (CPR) in an inpatient setting.
METHODS: We conducted a population-based cross-sectional study using the
Nationwide Inpatient Sample databases (2002-2011). International Classification
of Diseases, 9th Revision, Clinical Modification codes were used to define cases,
comorbidities, and clinical outcomes. Rates of CPR among study groups were
calculated by patient and hospital characteristics. Survey logistic regression
was used to estimate adjusted odds ratios (ORs) that represent the association
between pregnancy status and mortality after CPR. Joinpoint regression was used
to describe temporal trends in CPR and mortality rates. RESULTS: During the study
period, 5,923 women (13-49 years) received inpatient CPR annually.
Cardiopulmonary resuscitation rates increased significantly from 2002 to 2011, by
6.4% and 3.8% annually, for pregnant and nonpregnant women, respectively. In
hospital mortality rates after CPR were lower among pregnant women 49.4% (45.4
53.4) than nonpregnant women 71.1% (70.1-72.2), even after adjusting for
confounders (adjusted OR 0.46, 95% confidence interval 0.39-0.56). CONCLUSION:
Cardiopulmonary resuscitation in an inpatient pregnant woman is associated with
improved survival compared with this procedure in nonpregnant women. Elucidating
reasons behind this association could help to improve CPR outcomes in both
pregnant and nonpregnant women.
PMID- 27607875
TI - Spontaneous Coronary Artery Dissection in Pregnancy: What Every Obstetrician
Should Know.
AB - Spontaneous coronary artery dissection is a major cause of myocardial infarction
in pregnancy and the postpartum period. It occurs predominantly in young women
with few or no conventional risk factors for atherosclerosis and has been
clinically underrecognized. Treatment differs from that of myocardial infarction
as a result of atherosclerosis and the diagnosis should be considered in all
parturient and postpartum patients with acute coronary syndrome. Complications of
spontaneous coronary artery dissection include recurrence, congestive heart
failure, and death. Thus, specialist obstetrician-gynecologists and maternal
fetal medicine specialists need to gain knowledge of spontaneous coronary artery
dissection to improve outcomes.
PMID- 27607876
TI - Regular Exercise to Prevent the Recurrence of Gestational Diabetes Mellitus: A
Randomized Controlled Trial.
AB - OBJECTIVE: To investigate the effect of a supervised home-based exercise program
on the recurrence and severity of gestational diabetes mellitus (GDM) together
with other aspects of maternal health and obstetric and neonatal outcomes.
METHODS: This randomized controlled trial allocated women with a history of GDM
to an exercise intervention (14-week supervised home-based stationary cycling
program) or to a control group (standard care) at 13+/-1 weeks of gestation. The
primary outcome was a diagnosis of GDM. Secondary outcomes included maternal
fitness, psychological well-being, and obstetric and neonatal outcomes. A sample
size of 180 (90 in each group) was required to attain 80% power to detect a 40%
reduction in the incidence of GDM. RESULTS: Between June 2011 and July 2014, 205
women provided written consent and completed baseline assessments. Of these, 33
(16%) were subsequently excluded as a result of an elevated baseline oral glucose
tolerance test (OGTT), leaving 172 randomized to exercise (n=85) or control
(n=87). Three women miscarried before the assessment of outcome measures
(control=2; exercise=1). All remaining women completed the postintervention OGTT.
The recurrence rate of GDM was similar between groups (control 40% [n=34];
exercise 40.5% [n=34]; P=.95) and the severity of GDM at diagnosis was unaffected
by the exercise program with similar glucose and insulin responses to the OGTT
(glucose 2 hours post-OGTT 7.7+/-1.5 compared with 7.6+/-1.6 mmol/L; P>.05).
Maternal fitness was improved by the exercise program (P<.01) and psychological
distress was reduced (P=.02). There were no differences in obstetric and neonatal
outcomes between groups (P>.05). CONCLUSION: Supervised home-based exercise
started at 14 weeks of gestation did not prevent the recurrence of GDM; however,
it was associated with important benefits for maternal fitness and psychological
well-being. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
https://clinicaltrials.gov, NCT01283854.
PMID- 27607877
TI - Deceased Donor Uterine Transplantation: Innovation and Adaptation.
AB - This commentary endeavors to share our practical experience in developing and
implementing the first uterine transplant clinical trial in the United States.
Uterine transplant is a promising novel treatment for uterine factor infertility.
After reported successful live births after uterine transplant in Sweden,
research teams around the world are either embarking on or are considering the
development of uterine transplant protocols. Our observations on the applied
rather than theoretical aspects of uterine transplantation research in human
subjects are detailed in this article. Important among these considerations are
composing a broad and experienced multidisciplinary team as well as performing
adequate preclinical preparations, including ideally animal studies and practice
organ procurements. Ethical preparation is tantamount to clinical preparation for
the complexities inherent in uterine transplant, and our suggestions for updating
the current ethical criteria for uterine transplant are outlined here. We also
describe our perspectives on the strengths and weaknesses of living compared with
deceased donor models. Finally, we describe how a strong program can recover and
adapt in the face of setbacks to continue a path toward innovation.
PMID- 27607879
TI - Maternal Marijuana Use and Adverse Neonatal Outcomes: A Systematic Review and
Meta-analysis.
AB - OBJECTIVE: To estimate whether marijuana use in pregnancy increases risks for
adverse neonatal outcomes and clarify if any increased risk is attributable to
marijuana use itself or to confounding factors such as tobacco use. DATA SOURCES:
Two authors performed a search of the data through August 2015 utilizing PubMed,
Embase, Scopus, Cochrane reviews, ClinicalTrials.gov, and Cumulative Index to
Nursing and Allied Health. METHODS OF STUDY SELECTION: We looked at observational
studies that compared rates of prespecified adverse neonatal outcomes in women
who used marijuana during pregnancy with women who did not. TABULATION,
INTEGRATION, AND RESULTS: Two authors independently extracted data from the
selected studies. Primary outcomes were low birth weight (less than 2,500 g) and
preterm delivery at less than 37 weeks of gestation. Secondary outcomes were
birth weight, gestational age at delivery, small for gestational age, level II or
greater nursery admission, stillbirth, spontaneous abortion, low Apgar score,
placental abruption, and perinatal death. DerSimonian-Laird random-effects models
were used. We assessed heterogeneity using the Q test and I statistic. Stratified
analyses were performed for the primary outcomes and pooled adjusted estimates
were calculated. We included 31 studies that assessed the effects of maternal
marijuana use on adverse neonatal outcomes. Based on pooled unadjusted data,
marijuana use during pregnancy was associated with an increased risk of low birth
weight (15.4% compared with 10.4%, pooled relative risk [RR] 1.43, 95% confidence
interval [CI] 1.27-1.62) and preterm delivery (15.3% compared with 9.6%, pooled
RR 1.32, 95% CI 1.14-1.54). However, pooled data adjusted for tobacco use and
other confounding factors showed no statistically significant increased risk for
low birth weight (pooled RR 1.16, 95% CI 0.98-1.37) or preterm delivery (pooled
RR 1.08, 95% CI 0.82-1.43). CONCLUSION: Maternal marijuana use during pregnancy
is not an independent risk factor for adverse neonatal outcomes after adjusting
for confounding factors. Thus, the association between maternal marijuana use and
adverse outcomes appears attributable to concomitant tobacco use and other
confounding factors.
PMID- 27607878
TI - Distinguishing Arterial Ischemic Stroke From Hypoxic-Ischemic Encephalopathy in
the Neonate at Birth.
AB - OBJECTIVE: To identify perinatal risk factors that can distinguish arterial
ischemic stroke from hypoxic-ischemic encephalopathy at birth. METHODS: This is a
cohort study of all neonates born at 35 weeks of gestation or greater admitted to
our neonatal intensive care unit from January 1, 2010, to December 31, 2015, that
compares neonates with stroke with those with hypoxic-ischemic encephalopathy
undergoing whole-body hypothermia with abnormal brain magnetic resonance imaging.
RESULTS: During this 6-year period, there were 22 neonates with stroke and 47
with hypoxic-ischemic encephalopathy undergoing whole-body hypothermia with
abnormal magnetic resonance imaging. Three neonates triaged to hypothermia
initially thought to have hypoxic-ischemic encephalopathy were later diagnosed
with stroke. All neonates with stroke had a negative thrombophilia workup.
Neonates with stroke had a significantly higher incidence of seizures and
increased initial platelet counts on univariate analysis. A multivariable model
of variables with P<.1 on univariate analysis present within 6 hours of birth
found significant increases in nonreassuring fetal heart rate tracings, sentinel
events, low Apgar score at 5 minutes, and metabolic acidosis at birth with
hypoxic-ischemic encephalopathy. Stroke was associated with a significantly
increased initial platelet count. CONCLUSION: Stroke is associated with increased
initial platelet counts and is not associated with cesarean delivery for
nonreassuring fetal heart rate tracings, sentinel events, or perinatal metabolic
acidosis. Stroke is a form of neonatal brain injury not associated with perinatal
risk factors that allow early identification.
PMID- 27607880
TI - 17-alpha Hydroxyprogesterone Caproate for the Prevention of Recurrent Preterm
Birth: One Size May Not Fit All.
AB - Spontaneous preterm birth is a syndrome with many causes and thus unresponsive to
a single intervention. It logically follows that patients with a prior
spontaneous preterm birth are a heterogeneous group unlikely to respond equally
to a single preventive intervention such as 17-alpha hydroxyprogesterone
caproate. Further confounding this issue is our fundamental lack of knowledge
about the mechanism(s) by which 17-alpha hydroxyprogesterone caproate reduces
preterm birth. Recently, studies demonstrating that responders and nonresponders
can be identified based on obstetric history, genotype, physical characteristics,
and behavioral factors have begun to provide clues into both 17-alpha
hydroxyprogesterone caproate's mechanism and the pathophysiology of recurrent
preterm birth and may allow for more targeted therapy. These studies lend support
to speculation that inflammation or nitric oxide metabolism may be common threads
between 17-alpha hydroxyprogesterone caproate's mechanism and preterm birth
prevention. It will remain critically important to avoid the temptation to regard
prior spontaneous preterm birth as a single disease entity amenable to a single
treatment.
PMID- 27607881
TI - Structural Failure Sites in Anterior Vaginal Wall Prolapse: Identification of a
Collinear Triad.
AB - OBJECTIVE: To test the null hypothesis that six factors representing potential
fascial and muscular failure sites contribute equally to the presence and size of
a cystocele: two vaginal attachment factors (apical support and paravaginal
defects), two vaginal wall factors (vaginal length and width), and two levator
ani factors (hiatus size and levator ani defects). METHODS: Thirty women with
anterior-predominant prolapse (women in a case group) and 30 women in a control
group underwent three-dimensional stress magnetic resonance imaging. The location
of the anterior vaginal wall at maximal Valsalva was identified with the modified
Pelvic Inclination Coordinate System and the six factors measured. Analysis
included repeated-measure analysis of variance, logistic regression, and stepwise
linear regression. RESULTS: We identified a collinear triad consisting of apical
location, paravaginal location, and hiatus size that were not only the strongest
predictors of cystocele size, but were also highly correlated with one another
(r=0.84-0.89, P<.001) for the presence and size of the prolapse. Together they
explain up to 83% of the variation in cystocele size. Among the less significant
vaginal factors, vaginal length explained 19% of the variation in cystocele size,
but no significant difference in vaginal width existed. Women in the case group
were more likely to have abnormalities in collinear triad factors (up to 80%)
than vaginal wall factors (up to 23.3%). Combining the strongest collinear triad
with the vaginal factors, the model explained 92.5% of the variation in cystocele
size. CONCLUSION: Apical location, paravaginal location, and hiatus size are
highly correlated and are strong predictors of cystocele presence and size.
PMID- 27607882
TI - Discovery of the aryl heterocyclic amine insecticides: synthesis, insecticidal
activity, field results, mode of action and bioavailability of a leading field
candidate.
AB - BACKGROUND: gamma-Amino butyric acid (GABA) antagonists are proven targets for
control of lepidopteran and other pests. New heterocyclic compounds with high
insecticidal activity were discovered using a competitive-intelligence-inspired
scaffold-hopping approach to generate analogs of fipronil, a known GABA
antagonist. These novel aryl heterocyclic amines (AHAs) displayed broad-spectrum
activity on a number of chewing insect pests. RESULTS: Through >370 modifications
of the core AHA structure, a 7-pyrazolopyridine lead molecule was found to
exhibit much improved activity on a number of insect pests. In field trial
studies, its performance was 2-4 times lower than commercial standards and also
appeared to be species dependent, with good activity seen for larvae of
Spodoptera exigua, but inactivity on larvae of Trichoplusia ni. CONCLUSION: An
extensive investigational biology effort demonstrated that these AHA analogs
appear to have multiple modes of action, including GABA receptor antagonism and
mitopotential or uncoupler activity. The limited capability in larvae of T. ni to
convert the lead molecule to its associated open form correlates with the low
toxicity of the lead molecule in this species. This work has provided information
that could aid investigations of novel GABA antagonists. (c) 2016 Society of
Chemical Industry.
PMID- 27607884
TI - [Idiopathic Progressive Subglottic Stenosis: Surgical Techniques].
AB - Idiopathic subglottic stenosis is a disease characterized by slow, progressive
scarring and constriction of the subglottic airway. It almost always occurs in
females between the 3rd and 5th decade of life. Symptoms are frequently
misinterpreted as asthma and patients are referred for endoscopic evaluation only
when asthma medications fail to alleviate their symptoms. Treatment options can
be divided into endoscopic and open surgical techniques. Microlaryngoscopic scar
reduction by laser followed by balloon dilation usually delivers good short-term
results. However, the majority of patients will experience restenosis within a
short period of time. Open surgical correction techniques are based on a complete
removal of the affected airway segment. This must be combined with various
extended resection techniques in patients with advanced stenosis. Depending on
the extent and severity of the stenosis the following surgical techniques are
required: standard cricotracheal resection (Grillo's technique), cricoplasty with
dorsal and lateral mucosaplasty, or a combination of resection and enlargement
techniques using rib cartilage grafts. In experienced centres, success rates of
over 95 % are reported with good functional outcome of voice and deglutition.
PMID- 27607883
TI - The mitogen-activated protein kinase Slt2 modulates arsenite transport through
the aquaglyceroporin Fps1.
AB - Arsenite is widely present in nature; therefore, cells have evolved mechanisms to
prevent arsenite influx and promote efflux. In yeast (Saccharomyces cerevisiae),
the aquaglyceroporin Fps1 mediates arsenite influx and efflux. The mitogen
activated protein kinase (MAPK) Hog1 has previously been shown to restrict
arsenite influx through Fps1. In this study, we show that another MAPK, Slt2, is
transiently phosphorylated in response to arsenite influx. Our findings indicate
that the protein kinase activity of Slt2 is required for its role in arsenite
tolerance. While Hog1 prevents arsenite influx via phosphorylation of T231 at the
N-terminal domain of Fps1, Slt2 promotes arsenite efflux through phosphorylation
of S537 at the C terminus. Our data suggest that Slt2 physically interacts with
Fps1 and that this interaction depends on phosphorylation of S537. We hypothesize
that Hog1 and Slt2 may affect each other's binding to Fps1, thereby controlling
the opening and closing of the channel.
PMID- 27607885
TI - [Decortication in Pleural Empyema: Reasonable Effects on Lung Function?].
AB - Parapneumonic pleural effusion (PPE) occurring in early-stage (stage I) pleural
empyema (PE) can be managed by chest tube drainage, which should be performed as
soon as possible, to achieve re-expansion of the pulmonary parenchyma. Chronic
disease leads to fibrin deposits on both pleural surfaces (stage II), followed by
a thickened pleura peel (stage III). A trapped or compressed lung can only be
released by surgical decortication, which may be performed with a minimally
invasive approach (video-assisted thoracoscopy) or an open technique
(thoracotomy). This article reviews effects on pulmonary function after
decortication in chronic empyema patients. MATERIAL AND METHODS: Selective
literature research using Medline (key words: pleural empyema, decortication,
lung function). A comparative analysis was performed on functional parameters
obtained before and after surgical decortication in patients with chronic pleural
empyema. RESULTS: Decortication in chronic PE significantly enhanced spirometric
parameters (FEV1, VC/FVC) in all analysed studies. Considerable differences were
observed regarding the mean follow-up time (early postoperative to several months
after surgery). Computed tomography scans were usually analysed after a minimum
of 6 months postoperatively. Measurements of anterior-posterior and transverse
diameters as well as volume quantification of the operated and non-operated lung
were performed in pre- and postoperative imaging. Statistical comparison revealed
a significant decrease in thoracic asymmetry. In addition to static and dynamic
pulmonary performance, pulmonary perfusion improved significantly after
decortication as demonstrated by lung perfusion scans performed immediately after
surgery and during a period of 7 to 10 months thereafter. CONCLUSION: Surgical
decortication in chronic pleural empyema improves lung function and increases
perfusion. Besides a significant enhancement of spirometric parameters, re
expansion of the diseased lung leads to equalisation of thoracic asymmetry and
may even prevent loss of volume in the affected lung.
PMID- 27607886
TI - [Lung Volume Reduction Surgery - State of the Art 2016].
AB - In a number of large case series in the mid-1990s, lung volume reduction surgery
(LVRS) was shown to reduce dyspnoea and improve pulmonary function and quality of
life in patients with advanced pulmonary emphysema. The large randomised National
Emphysema Treatment Trial (NETT) confirmed this in the early 2000s and also
demonstrated that selected patients live longer after surgery. Patient selection
is crucial to the success of the procedure and should be performed at a
specialised experienced centre with a multidisciplinary team approach on
emphysema treatment. The upper-lobe predominant heterogeneous type of emphysema
is the best indication, but there are other types of emphysema morphology that
are also eligible for surgery, if ideally chosen. Nowadays there is also growing
evidence for positive effects after different types of bronchoscopic lung volume
reduction (BLVR) with increasing quality. These methods add to the range of
multimodal emphysema treatment.
PMID- 27607887
TI - [Tracheobronchoplasty for Severe Diffuse Tracheomalacia].
AB - Patients with diffuse airway instability due to tracheobronchomalacia or
excessive dynamic airway collapse are typically highly symptomatic, with marked
dyspnoea, recurrent bronchopulmonary infections and excruciating intractable
cough. Silicone stents achieve immediate symptom control, but are - due to the
typical complications associated with stent treatment - usually not an option for
long-term treatment. The aim of surgical intervention is definitive stabilisation
of the trachea and of both main bronchi by posterior splinting of the Paries
membranaceus with a polypropylene mesh. This operation is an appropriate
treatment option for patients with documented severe tracheobronchomalacia or
excessive dynamic airway collapse and is ultimately the only therapy that can
achieve permanent symptom control. The success of the operation, however, depends
on many factors and requires close interdisciplinary collaboration.
PMID- 27607888
TI - [Surgical Therapy of Acquired Unilateral Diaphragmatic Paralysis: Indication and
Results].
AB - Unilateral elevation of the diaphragm may be due to various causes and requires
further elucidation when the aetiology is unknown. Elevation of the diaphragm is
often caused by diaphragmatic paralysis, either due to damage to the phrenic
nerve or to the phrenic muscle. Patients typically complain of increased
respiratory distress when lying down, bending or swimming. Basic diagnostic
testing consists of a chest X-ray, as well as spirometry and computer tomography
of the neck and chest. In many cases, no cause can be identified for the
diaphragmatic paralysis. In symptomatic patients, diaphragm plication leads to
fixation and thus to a reduction in the paradoxal respiratory movement of the
paralysed diaphragm. In a large majority of studies, this results in significant
and lasting improvement in vital capacity and respiratory distress. Spontaneous
recovery of diaphragm paralysis is possible, even after several months, so a
waiting period of at least 6 months should elapse before diaphragmatic plication
is performed, if the clinical situation allows. The procedure can be performed
minimally invasively, with low morbidity and mortality. When cutting the phrenic
nerve, a nerve suture is recommended, if possible, or otherwise diaphragm
plication during the procedure, especially in the case of pneumonectomy. This
review provides an overview of the causes, pathophysiology, symptoms, diagnosis,
therapy and results of diaphragmatic plication in acquired, unilateral
diaphragmatic paralysis in adults, and suggests an algorithm for diagnostic
testing and therapy.
PMID- 27607890
TI - [Not Available].
PMID- 27607889
TI - [Management of the Therapy of Pulmonary Sequestration: A Retrospective
Multicentre Study].
AB - BACKGROUND: Pulmonary sequestration is a rare pulmonary malformation whose
complex pathogenesis is not completely understood. Extrapulmonary sequestrations
are always hereditary malformations and are usually diagnosed during childhood.
Some intralobar sequestrations in adults, by contrast, seem to be acquired. The
clinical presentation is non-specific and often misinterpreted, which results in
delayed diagnosis. Surgical resection continues to be the gold standard. Despite
the low incidence, new technologies developed in the past few decades, e.g.
preoperative interventional angiology procedures and video-assisted lung
resection, have changed the management of the disease. METHODS: A prospective
data collection was performed on adult patients who had undergone surgical
resection of a pulmonary sequestration in four different centres during a period
of 23 years. These data were retrospectively analysed. RESULTS: A total of 14
patients with intralobar sequestrations (n = 11, 79 % left lower lobe) underwent
surgical resection. The male/female ratio was 8/6 (median age 50 years). Non
specific pulmonary symptoms such as recurrent infections had a high prevalence (n
= 6, 42 %). Two patients had haemoptysis. Three patients were asymptomatic. All
patients had a chest CT, 7 patients had an additional abdominal CT, while 10
underwent angiography. Preoperative embolization was performed in 5 of these
patients (branches of the thoracic aorta: in 2 cases, branches of abdominal
aorta: in 2 cases, and branches of both: in 1 case). Resection was mostly
performed with an open surgical approach (n = 12, 86 %). Most patients had a non
anatomic pulmonary resection (n = 8, 57 %). In 7 patients, a microbiologic
examination revealed a superinfection with Streptococcus pneumoniae, while 1
patient had an invasive mycosis with Candida albicans. CONCLUSION: In patients
with non-specific pulmonary symptoms and undetermined lesions, especially in the
lower lobes, pulmonary sequestrations must be considered in the differential
diagnostic evaluation even in adult and elderly patients. If there are no
contraindications, surgical removal is basically recommended and may be minimally
invasive in selected cases. The planning of the resection can be facilitated by
preoperative evaluation of the arterial supply (branches of the thoracic or
abdominal aorta, or both). In cases with haemoptysis or blood supply over the
abdominal aorta, preoperative embolization is indicated.
PMID- 27607891
TI - [Functional Outcome after Chest Wall Stabilisation].
AB - This overview reviews the current literature to compare the functional results
after surgical and conservative treatment of patients with flail chest and
multiple rib fractures. Regarding functional aspects, patients in the early phase
after a thoracic trauma are those that benefit most from the stabilisation of the
chest wall by internal fixation of the ribs. Patients recover faster from
restrictive respiratory disorders, have less pain and return to the workplace
earlier after an operation compared with those that receive conservative
treatment. In the medium term, however, patients that are treated conservatively
also achieve normal pulmonary function values and become free of pain. The period
of convalescence after blunt thoracic trauma is generally underestimated. Future
studies of the functional outcome after severe chest injuries should take this
into account and the development of functional parameters should be monitored for
at least 24 months. A prospective data collection of early and long-term surgical
results in registries would be suitable to evaluate benefits and indications of
chest wall stabilisation.
PMID- 27607892
TI - Characterization of Lipid-Based Hexosomes as Versatile Vaccine Carriers.
AB - Subunit vaccines typically show insufficient immunogenicity. To address this
issue, we developed a novel self-adjuvanting particulate carrier system based
upon the lipids phytantriol (Phy) and mannide monooleate (MaMo). Phy is a lipid
known to form nonlamellar phases in fully hydrated systems, whereas MaMo has been
found to promote immune responses in emulsion form. A bulk phase composition of
Phy/MaMo (14 wt %) showed hexagonal (HII) phase behavior over a practical
temperature range (including room and body temperature), and was therefore used
for particle development. Hexosomes stabilized with different concentrations of
either poloxamer 407, Myrj 59, or Pluronic F108 were successfully prepared. To
demonstrate the versatile nature of these systems, the particles were further
modified with either positively or negatively charged lipids and loaded with
model antigens, while maintaining the HII structure. These hexosomes are
structurally robust and amenable to customization, rendering them suitable as
antigen delivery carriers.
PMID- 27607893
TI - Case of anti-transcriptional intermediary factor-1-positive dermatomyositis
associated with breast cancer developing over 10 years.
PMID- 27607894
TI - The accuracy of preoperative imaging in measuring the length of the ileocolic
segment affected by Crohn's disease: a prospective cohort study.
AB - AIM: The study aimed to evaluate the accuracy of imaging for measurement of the
length of the ileocolic segment affected by Crohn's disease. METHOD: Fifty-four
consecutive patients who underwent resection between 2011 and 2014 for ileocolic
Crohn's disease were prospectively studied. All had preoperative MR or CT
enterography. Two independent radiologists measured the length of the diseased
intestinal segment. The measurements were compared with the length of disease
assessed on pathology of the non-fixed surgical specimen. RESULTS: The median
preoperative length of the Crohn's disease segment on imaging was 20.5 (2-73) cm
and 20 (3-90) cm, as measured by the two radiologists. Interobserver agreement
was substantial (kappa = 0.69) with a correlation coefficient (r) of 0.82 (P <
0.001). The median length of the Crohn's disease segment on pathological
examination was 16.5 (2-75) cm and was closely correlated with the radiological
measurement (r = 0.76, P < 0.001). The length of the Crohn's disease segment on
imaging was correct to within 5 cm of the value on pathology. It was correct in
30 (55%) patients and was underestimated and overestimated in 6 (11.1%) and 18
(33.3%). A length of disease of less than 20 cm found on imaging in 26 patients
was confirmed in 25 (96%) on pathology, whereas a length of more than 20 cm found
on imaging in 28 patients was confirmed in 18 (64%) on pathology. The
sensitivity, specificity, positive predictive value, negative predictive value
and overall accuracy of imaging for predicting a length of less than 20 cm were
71%, 95%, 96%, 64% and 79%. CONCLUSION: Imaging accurately identifies the length
of the ileocolic segment of Crohn's disease when it is 20 cm or less on
pathological examination. In patients with more extensive disease, imaging tends
to overestimate the length and should be interpreted with caution.
PMID- 27607895
TI - Rituximab therapy in primary Sjogren's syndrome with interstitial lung disease: a
retrospective cohort study.
AB - OBJECTIVES: Interstitial lung disease (ILD) is one of the major systemic
manifestations of primary Sjogren's syndrome (pSS). The aim of this study was to
evaluate the therapeutic effect of rituximab on pSS patients with ILD. METHODS:
Pulmonary function test results, including diffusing capacity for carbon monoxide
(DLCO) and DLCO/alveolar volume (Va) ratio, and high-resolution computed
tomography (HRCT) findings/scores in ten pSS patients with ILD treated with
rituximab were retrospectively investigated. Global disease, fatigue, dryness of
eyes and mouth, shortness of breath, and cough were assessed by visual analogue
scales (VAS, 0-100 mm). RESULTS: At 6 months after rituximab treatment,
improvement in pulmonary function was observed (from 49.3+/-12.6 to 56.9+/-11.4%
for DLCO, p=0.011; from 74.4+/-15.8 to 85.6+/-10.3% for DLCO/Va, p=0.021).
Similarly, significant improvement of subjective symptoms were also noted after
treatment (VAS global disease, from 62.0+/-11.4 to 26.0+/-10.8 mm, p<0.001; VAS
fatigue, from 38.0+/-23.0 to 18.0+/-7.9 mm, p=0.006; VAS dryness of eyes, from
53.0+/-24.4 to 29.0+/-13.7 mm, p=0.004; VAS dryness of mouth, from 45.0+/-14.3 to
28.0+/-9.2 mm, p=0.001; VAS shortness of breath, from 64.0+/-16.5 to 31.0+/-16.0
mm, p<0.001; VAS cough, from 42.0+/-23.5 to 18.0+/-10.3 mm, p=0.011). The mean
HRCT score decreased after rituximab therapy although to a lesser extent (from
8.7+/-4.1 to 7.6+/-4.6, p=0.419). An adverse event was observed in only one
patient who had non-fatal pneumonia 4 months after rituximab infusion.
CONCLUSIONS: Rituximab was effective in improving clinical symptoms and gas
exchange, and in stabilising HRCT score in pSS patients with ILD.
PMID- 27607897
TI - Using the 'windows method' for undergraduate consultation skills feedback: GP
tutors' experiences.
PMID- 27607896
TI - Community Needs Assessment After Microcystin Toxin Contamination of a Municipal
Water Supply - Lucas County, Ohio, September 2014.
AB - On August 1, 2014, routine testing at the Collins Park Water Treatment Plant in
Lucas County, Ohio, revealed microcystin toxin levels in drinking water had
reached 3.19 MUg/L, surpassing the Ohio Environmental Protection Agency (EPA)
drinking water advisory threshold of 1.0 MUg/L. Microcystin is a hepatoxin
released by cyanobacteria in certain harmful algal blooms. Exposure to
microcystin has been associated with gastrointestinal and hepatic illness in both
humans and animals (1-3). On August 2, a do-not-drink advisory was issued,
warning community members not to drink, boil, or use the water for cooking or
brushing teeth. Public health officials used traditional and social media outlets
to disseminate public health messages to affected communities. On August 4, 2014,
the advisory was lifted after multiple water samples confirmed microcystin toxin
levels had dropped below the advisory threshold. To assess communication
strategies, water exposure, and household needs, the Ohio Department of Health
(ODH) and Toledo-Lucas County Health Department (TLCHD) conducted a Community
Assessment for Public Health Emergency Response (CASPER) in Lucas County. Most
households (88.1%) reported hearing about the advisory the morning it was issued,
but 11% reported drinking and 21% reported brushing teeth with municipal water
during the advisory. Household members reported physical (16%) and mental (10%)
health concerns that they believed were related to the advisory and activity
disruptions including temporarily staying outside of the home (6%) during the
advisory and continued use of alternative water sources after the advisory was
lifted (82%). During a do-not-drink advisory, governmental agencies and community
partners need to engage in joint prevention and response efforts to decrease
water exposure and prevent activity disruptions.
PMID- 27607898
TI - Inflammatory Bowel Disease: Changing Associations to Mechanisms.
AB - Managing the health of individual patients suffering from complex disorders is a
challenge and is costly. Inflammatory bowel disease (IBD) is a prototypic complex
disorder of the small and large intestines. Susceptibility is complex, severity
is variable, and response to treatment is unpredictable. Di Narzo et al. (Clin
Transl Gastroenterol 7: e177; doi:10.1038/ctg.2016.34) bring diverse teams of
physicians and scientists together to break down the mechanisms of IBD by linking
pathogenic genetic variants with altered gene expression in specific cell types
causing IBD. Framing new findings in the context of other complex diseases
provides a roadmap for predictive medicine.
PMID- 27607899
TI - Association between LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms and
diabetic retinopathy of type 2 diabetes mellitus in the Chinese Han population.
AB - BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular
complications of diabetes. The present study aimed to identify a possible
connection between gene polymorphisms and the risk of developing DR. MATERIALS
AND METHODS: A total of 319 patients with type 2 diabetes mellitus (T2DM) were
selected. All patients underwent a complete eye examination. Based on this, the
patients with T2DM were divided into two subgroups: 175 patients with retinopathy
(DR) and 144 patients without retinopathy (NDR). We calculated the genotype
frequencies of case and control subjects using the chi-squares test. The odds
ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional
logistic regression adjusted for age and sex. RESULTS: The finding by analysis is
that the mean of duration of diabetes, total cholesterol (TC), triglycerides
(TG), low-density lipoprotein (LDL), glomerular filtration rate and C-peptide
were significantly different between DR and NDR. We found significant differences
in cystatin-C concentrations with LEKR1-CCNL1 rs13064954 and NOS3 rs3918227 of
different genotypes. Significant differences in serum TG levels were seen among
the three genotypes of MTHFR rs1537516. Subjects carried the T allele of IGSF21
KLHDC7A rs3007729 had higher serum LDL concentrations (p = 0.015). In the allele
model, LEKR1-CCNL1 rs13064954 decreased the risk of DR (OR =0.57, 95% CI = 0.34
0.96, p = 0.032). Under the dominant model, the IGSF21-KLHDC7A rs3007729 CT-TT
genotype increased the risk of DR (OR =1.84, 95% CI = 1.14-2.99, p = 0.013).
CONCLUSIONS: Our results suggest that LEKR1-CCNL1 and IGSF21-KLHDC7A influence
the development of DR.
PMID- 27607900
TI - Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities
for an Established Class of Drugs?
AB - Novel antibiotics are urgently needed to combat the rise of infections due to
drug-resistant microorganisms. Numerous natural nucleosides and their
synthetically modified analogues have been reported to have moderate to good
antibiotic activity against different bacterial and fungal strains. Nucleoside
based compounds target several crucial processes of bacterial and fungal cells
such as nucleoside metabolism and cell wall, nucleic acid, and protein
biosynthesis. Nucleoside analogues have also been shown to target many other
bacterial and fungal cellular processes although these are not well characterized
and may therefore represent opportunities to discover new drugs with unique
mechanisms of action. In this Perspective, we demonstrate that nucleoside
analogues, cornerstones of anticancer and antiviral treatments, also have great
potential to be repurposed as antibiotics so that an old drug can learn new
tricks.
PMID- 27607901
TI - Stepwise Regioselective Hydrogenation of cis-2-C60 (CF2 )2 Homofullerene with
[6,6]-Open/Closed Valence Tautomerism.
AB - The homofullerene compound cis-2-C60 (CF2 )2 , which has an unusual kind of
open/closed valence tautomerism undergoes consecutive regioselective
hydrogenation at bridgehead carbon atoms upon reduction with Zn/Cu couple in H2 O
toluene mixture. The tautomerism barrier in cis-2-C60 (CF2 )2 is negligible in
the neutral state, whereas negative charging both impedes tautomeric
transformation and promotes regioselective addition of electrophilic species at
the bridgehead carbon atoms. In light of this observation, two novel
homofullerene derivatives, mixed [6,6]-open/closed C60 (CF2 )2 H2 and [6,6]-open
cis-2-C60 (CF2 )2 H4 , were synthesized and their structures were unambiguously
determined by means of single crystal X-ray crystallography and NMR spectroscopy.
PMID- 27607902
TI - Gender as a key factor in trace metal and metalloid content of human scalp hair.
A multi-site study.
AB - This multi-site study discusses the content of metals and metalloids (MM) in
scalp hair of children, living in different environmental contexts, with the
purpose of verifying if hair level of some MM is distinctively gender-specific. A
total of 943 hair samples (537 females and 406 males) from adolescents were
analyzed for their content of Al, As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Rb,
Sb, Se, Sr, U, V and Zn. Elemental quantification was performed by ICP-MS. The
obtained data identified different metal distributions in adolescent girls which
exhibited significantly higher hair concentrations of some trace metals,
especially Sr, Zn and Ni, than boys. On the base of the median value, hair of
female donors contained 3.8 times more Sr (6.6MUg/g) than males (1.7MUg/g).
Highest concentrations of Zn in females were observed in samples from the mining
area of Sardinia (587MUg/g). Nickel showed significant differences resulting 2.5
fold higher in female hair. Regardless of the residence site, these elements
resulted always significantly different (at p<0.01) between female and male
indicating that gender is a confounding factor that has to be more extensively
considered for a correct interpretation of metal profiles in human hair.
PMID- 27607903
TI - Historical sediment record and levels of PCBs in sediments and mangroves of Jobos
Bay, Puerto Rico.
AB - Polychlorinated biphenyls (PCBs) were quantified in 18 surface sediment samples,
1 sediment core, and several mangrove tissue samples collected in Jobos Bay,
Puerto Rico in September 2013. Total PCBs in surface sediments ranged from 0.42
to 1232ngg-1 dw. Generally, higher levels were observed near-shore close to urban
and industrial areas. The levels suggest significant pollution in Jobos Bay with
respect to PCBs. Two-thirds of the sites were dominated by lighter PCB congeners
(tri- to penta-chlorinated PCBs) while one-third had heavy PCB congeners (hexa-
to octa-chlorinated PCBs) dominant. Total PCBs in a sediment core indicated
levels fluctuating according to historical usage patterns. Total PCBs were
measured in mangal leaves (14-747ngg-1 dw), roots (0.26-120ngg-1 dw), and seeds
(16-93ngg-1 dw), suggesting bioaccumulation from sediments. This is the first
report of a historical profile of PCBs in the study area and of PCB
bioaccumulation in mangroves. This article provides new and useful information on
PCBs in the Caribbean area of the GRULAC region.
PMID- 27607904
TI - Modelling exposure of workers, residents and bystanders to vapour of plant
protection products after application to crops.
AB - Agricultural use of plant protection products can result in exposure of
bystanders, residents, operators and workers. Within the European Union (EU) FP7
project BROWSE, a tool based on a set of models and scenarios has been developed,
aiming to assess the risk of exposure of humans to these products. In the present
version of the tool only a first conservative tier is available for outdoor
vapour exposure assessment. In the vapour exposure evaluation, the target
concentrations in air at 10m distance from the edge of a treated field are
calculated for specific scenarios for each EU regulatory zone. These scenarios
have been selected to represent reasonable worst case volatilisation conditions.
The exposure assessment is based on a series of weekly applications in a five
year period to cover a wide range of meteorological conditions. The
volatilisation from the crop is calculated using the PEARL model and this PEARL
output provides the emission strength used as input for the short term version of
the atmospheric transport model OPS. The combined PEARL-OPS model is tested
against measurements from a field experiment. First results of this test show
that the mean concentration level was predicted fairly well. However, sometimes
the differences between observations and simulations were found to be
substantial. Improvements are suggested for the vapour exposure scenarios as well
as for further model development. In the current version of the BROWSE tool a
simplified procedure is used to assess single and multiple applications. The
actual period of application and the time of application during the day are
fixed, and the growth stage of the crop cannot be taken into account. Moreover,
competing processes such as penetration of the substance into the plant tissue
are not considered. The effect of these factors on the target exposure
concentrations is discussed.
PMID- 27607905
TI - Bioaccumulation of metals and PCBs in Raja clavata.
AB - The goal of this study was to assess stable isotopes profiles, metals
concentration and PCBs in Raja clavata muscle and liver, according to sex and
size, and to elucidate its suitability as a Mid-Atlantic biomonitor. The results
reflected bioaccumulation and suggested biomagnification processes for As and Hg
in muscle tissue. Cd, Cu and Zn were detected in high amounts in liver, Cr, Mn
and Rb were relatively stable and low, Pb was not detected and Sr was present in
muscle at high levels, decreasing with length. Hg and Se were strongly
correlated, suggesting a mitigation role. Both tissues presented low
concentrations of PCBs, especially the dioxin-like congeners, although always
higher in liver and not correlated with size. None of these contaminants exceed
EU legislated limits. However, they need to be monitored given study area's
location, volcanic nature and the expected increase of anthropogenic activity
related to future prospective mining activities and the establishment of the
Transatlantic Trade and Investment Partnership (TTIP) between Europe and the USA.
PMID- 27607906
TI - Chemical characterization and source apportionment of PM2.5 in a semi-arid and
petrochemical-industrialized city, Northwest China.
AB - Daily PM2.5 samples were collected in 2014 at a suburban petrochemical industrial
site and a downtown site in Lanzhou city, Northwest China. Major chemical
components in PM2.5, including water-soluble ions, metal elements, and organic
and elemental carbon (OC and EC) were determined. The chemical mass closure
method and the ISORROPIA II thermodynamic equilibrium model were used to
reconstruct PM2.5 mass and quantify the combinations of NH4+, SO42- and NO3- to
PM2.5. Positive matrix factorization (PMF) model was employed to apportion
potential sources of PM2.5. The annual average PM2.5 concentration was 93.7+/
49.6MUgm-3 at the suburban petrochemical industrial site and 88.9+/-52.0MUgm-3 at
the urban site, with the highest seasonal average in winter and the lowest in
summer at both sites. Mineral dust was identified as the highest contributor to
PM2.5 in spring, while water-soluble inorganic ions and carbonaceous aerosols
were the dominant chemical components in other seasons. The correlation
relationships between OC and EC and between K+ and EC suggested that coal
combustion and vehicle exhaust were the major sources of carbonaceous aerosols in
Lanzhou. Six major sources were identified by the PMF model. Coal combustion,
soil dust, traffic emissions, and secondary inorganic aerosols were the dominant
contributors, together accounting for 82% of PM2.5 mass.
PMID- 27607907
TI - Two distinct patterns of seasonal variation of airborne black carbon over Tibetan
Plateau.
AB - Airborne black carbon (BC) mass concentrations were measured from November 2012
to June 2013 at Ranwu and Beiluhe, located in the southeastern and central
Tibetan Plateau, respectively. Monthly mean BC concentrations show a winter
(November-February) high (413.2ngm-3) and spring (March-June) low (139.1ngm-3) at
Ranwu, but in contrast a winter low and spring high at Beiluhe (204.8 and
621.6ngm-3, respectively). By examining the meteorological conditions at various
scales, we found that the monthly variation of airborne BC over the southeastern
Tibetan Plateau (TP) was highly influenced by regional precipitation and over the
hinterland by winds. Local precipitation at both sites showed little impact on
the seasonal variation of airborne BC concentrations. Potential BC source regions
are identified using air mass backward trajectory analysis. At Ranwu, BC was
dominated by the air masses from the northeastern India and Bangladesh in both
winter and spring, whereas at Beiluhe it was largely contributed by air masses
from the south slope of Himalayas in winter, and from the arid region in the
north of the TP in spring. The winter and spring seasonal peak of BC in the
southern TP is largely contributed by emissions from South Asia, and this
seasonal variation is heavily influenced by the regional monsoon. In the northern
TP, BC had high concentrations during spring and summer seasons, which is very
likely associated with more efficient transport of BC over the arid regions on
the north of Tibetan Plateau and in Central Asia. Airborne BC concentrations at
the Ranwu sampling site showed a significant diurnal cycle with a peak shortly
after sunrise followed by a decrease before noon in both winter and spring,
likely shaped by local human activities and the diurnal variation of wind speed.
At the Beiluhe sampling site, the diurnal variation of BC is different and less
distinct.
PMID- 27607908
TI - Impacts of ethylenediurea (EDU) soil drench and foliar spray in Salix
sachalinensis protection against O3-induced injury.
AB - It is widely accepted that elevated levels of surface ozone (O3) negatively
affect plants. Ethylenediurea (EDU) is a synthetic substance which effectively
protects plants against O3-caused phytotoxicity. Among other questions, the one
still open is: which EDU application method is more appropriate for treating fast
growing tree species. The main aims of this study were: (i) to test if chronic
exposure of Salix sachalinensis plants to 200-400mgEDUL-1, the usually applied
range for protection against O3 phytotoxicity, is beneficial to plants; (ii) to
evaluate the effects of chronic exposure to elevated O3 on S. sachalinensis;
(iii) to assess the efficacy of two methods (i.e. soil drench and foliar spray)
of EDU application to plants; (iv) to investigate the appropriate concentration
of EDU to protect against elevated O3-induced damage in S. sachalinensis; and (v)
to compare the two methods of EDU application in terms of effectiveness and EDU
consumption. Current-year cuttings grown in infertile soil free from organic
matter were exposed either to low ambient O3 (AOZ, 10-h~28.3nmolmol-1) or to
elevated O3 (EOZ, 10-h~65.8nmolmol-1) levels during daylight hours. Over the
growing season, plants were treated every nine days with 200mL soil drench of 0,
200 or 400mgEDUL-1 or with foliar spray of 0, 200 or 400mgEDUL-1 (in two separate
experiments). We found that EDU per se had no effects on plants exposed to AOZ.
EOZ practically significantly injured S. sachalinensis plants, and the impact was
indifferent between the experiments. EDU did not protect plants against EOZ
impact when applied as soil drench but it did protect them when applied as 200
400mgL-1 foliar spray. We conclude that EDU may be more effective against O3
phytotoxicity to fast-growing species when applied as a spray than when applied
as a drench. Keymessage: Soil-drenched EDU was ineffective in protecting willow
plants against O3-induced injury, whereas foliar-sprayed EDU was effective even
at the concentration of 200mgL-1.
PMID- 27607909
TI - Pediatric Antipsychotic Use and Outcomes Monitoring.
AB - Antipsychotic (ATP) prescription rates have increased in children and adolescents
despite concern regarding the safety and effectiveness of ATP usage in community
populations. Rising safety concerns and uncertainty regarding ATP effectiveness
in children stress the need for improvement in routine clinical outcome
monitoring and research. Due to the growing number of children exposed to
atypical ATPs, studies assessing the risk/benefit ratio of administering ATPs in
this age group-especially in off-label conditions-become of high importance. The
Centre for Interventional Pediatric Psychopharmacology and Rare Diseases (CIPPRD)
uses a suite of instruments to monitor outcomes using the web-based
HealthTrackerTM, a health monitoring platform. The HealthTracker allows for
capture of symptoms, side effects, quality of life, patient experience, and
lifetime response to individualized treatments using a multi-informant multimodal
methodology. It enables the tracking of ongoing medical treatments and assists in
shared treatment decision-making, longitudinal patient centered outcome
monitoring, and helps optimize care. An example of its use in the CIPPRD is
provided to demonstrate how it can be used for ATP-related outcome monitoring in
complex neurodisability within routine clinical practice.
PMID- 27607910
TI - Update on treatment of cytomegalovirus infection in pregnancy and of the newborn
with congenital cytomegalovirus.
AB - PURPOSE OF REVIEW: The purpose of this review is to assess the recent studies of
therapy of pregnant women and neonates, aimed at preventing the consequences of
congenital cytomegalovirus (CMV) infection. RECENT FINDINGS: A recent randomized
controlled trial of treatment of CMV during pregnancy with hyperimmune globulin
did not show significant efficacy in prevention of foetal infection and
morbidity, although there was a trend towards improvement with treatment. Trials
of antiviral therapy of the mother during pregnancy have involved small numbers
only, confounded by ethical and practical difficulties, and further studies are
needed to demonstrate whether or not antivirals are useful and well tolerated in
this setting.Antiviral treatment of neonatal CMV acquired congenitally has been
studied in well controlled trials and the antiviral valganciclovir has shown
efficacy in reducing the more severe outcomes. Trials are ongoing of the use of
antivirals in less severe disease, although results are likely to take several
years. SUMMARY: Congenital CMV infection is the most frequent cause of congenital
malformation in developed countries, with a symptomatic prevalence of 0.64% of
all live births. Infection may result in neurodevelopmental delay, foetal or
neonatal death, and most frequently, sensorineural hearing loss. Successful
control of viral infections during pregnancy and in the newborn period is
essential in reducing early and late morbidity and mortality. Control of
congenital CMV infection may be via primary prevention methods such as reducing
contact with the pathogen, improved hygiene - both for the pregnant mother and
for the neonate, or secondary prevention via reduction of vertical transmission
from mother to foetus and reduction in consequences of infection by treatment of
infected pregnant women and infected neonates.
PMID- 27607911
TI - Treatment of hepatitis E virus.
AB - PURPOSE OF REVIEW: Over the last 10 years, it has become apparent that hepatitis
E virus (HEV) is a pathogen of global significance. In contrast to HEV in the
developing world, HEV in developed countries is caused by HEV genotypes 3 and 4,
which are enzoonotic with a porcine primary host and cause both acute and chronic
infection. Chronic infection occurs in the immunosuppressed, including transplant
recipients, and untreated can cause rapidly progressive cirrhosis. RECENT
FINDINGS: Ribavirin has been used successfully to treat acute hepatitis E in high
risk patients. Ribavirin monotherapy is the treatment of choice for patients
chronically infected with HEV, with sustained virological response (SVR) of
approximately 85%. A minority of chronically infected patients fail to achieve
SVR with ribavirin monotherapy, possibly because of viral mutants. The treatment
of patients who fail to achieve SVR with ribavirin monotherapy is problematic.
SUMMARY: Ribavirin is an effective treatment for hepatitis E, but further studies
are required to determine which other antiviral agents are of clinical utility in
treating HEV in the minority of patients who do not respond to ribavirin.
PMID- 27607912
TI - Repeated therapeutic lumbar punctures in cryptococcal meningitis - necessity
and/or opportunity?
AB - PURPOSE OF REVIEW: Overall, 50-70% of patients with cryptococcal meningitis have
raised intracranial pressure (ICP). Multiple international treatment guidelines
recommend repeated therapeutic lumbar punctures as adjunctive management. Here,
we review the recent evidence for the role of repeated lumbar punctures on
clinical outcome in cryptococcal meningitis and also review the increasing body
of data utilizing these repeated cerebrospinal fluid (CSF) samples as a window
into understanding immunopathogenesis of cryptococcal meningitis. RECENT
FINDINGS: Adjunctive dexamethasone led to higher adverse advents and disability
and poorer CSF fungal clearance. Performance of a therapeutic lumbar puncture is
associated with 69% relative survival protection. An activated innate immune
system in the CSF is associated with future cryptococcosis-associated immune
reconstitution inflammatory syndrome development. The zebrafish model is being
utilized in cryptococcal studies allowing live visualization of central nervous
system invasion. SUMMARY: Therapeutic lumbar punctures are a critical part of
cryptococcal meningitis management and CSF immunological assays are increasingly
being performed in research settings. Finer manipulation of CSF removal and safer
surgical techniques for intracranial pressure management applicable to resource
limited settings are needed. More precise and validated guidelines in resource
available settings would be an improvement for care. We look forward to
identifying a set of biomarkers, easily performed in routine laboratories or at
point-of-care, so as to translate these assays into clinical care. Wide-scale '
omic' studies are likely to be required in future cryptococcal meningitis studies
to improve our understanding of this deadly fungus.
PMID- 27607913
TI - Development of novel ligands for peptide GPCRs.
AB - Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a
G-protein coupled receptor (GPCR) are currently used in the treatment of type 2
diabetes. This review focuses on GPCRs from pancreatic beta-cells, including GLP
1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin,
pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY),
oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are
thought to have an increasing role in regulating peptide secretions namely short
fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain
fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119).
Several pre-clinical and clinical trials are currently ongoing in peptide GPCR
based therapies, including dual and triple agonist peptides which activate two or
more GPCRs simultaneously.
PMID- 27607914
TI - A rapid loop-mediated isothermal amplification (LAMP) method for detection of the
macrolide-streptogramin type B resistance gene msrA in Staphylococcus aureus.
AB - Macrolide-streptogramin type B resistance (the MSB phenotype) is a multidrug
resistance phenotype in Staphylococcus aureus conferred by the resistance gene
msrA. However, bacteria having the MSB phenotype are susceptible to lincosamides
and 16-membered ring macrolides, which makes profiling resistance genes necessary
and urgent for timely and appropriate use of antimicrobials. In this study, the
loop-mediated isothermal amplification (LAMP) assay was optimized for prompt
detection of the msrA gene. msrA gene sequences were obtained from the National
Center for Biotechnology Information (NCBI) database and primers were designed
using the LAMP primer designing software PrimerExplorer v.4, which together
recognize seven distinct regions of the msrA gene. The specific LAMP primer set
designed in this study could amplify the msrA gene within 25min at an isothermal
temperature of 62 degrees C. More importantly, the msrA gene could be detected at
a sensitivity as low as 100pg. Furthermore, this optimized LAMP assay provided
swift detection of the msrA gene even directly from human specimens. In
conclusion, this assay may have great clinical application potential for
detection of the msrA gene.
PMID- 27607915
TI - Ischemia/Reperfusion Injury Alters Sphingolipid Metabolism in the Gut.
AB - BACKGROUND: Intestinal ischemia/reperfusion injury (I/R) is a significant cause
of morbidity and mortality in surgical patients. Ceramide is a mediator of
apoptosis and has been implicated as increasing bacterial infection
susceptibility. The metabolite of ceramide, sphingosine, was recently shown to
play an important role in the cell-autonomous, innate immune response of the
upper respiratory tract by killing bacterial pathogens. The role of ceramide
and/or sphingosine after mesenteric I/R is unknown. We investigated the specific
effects of intestinal I/R on tissue ceramide and sphingosine concentration and
resulting susceptibility to bacterial invasion. METHODS: To simulate intestinal
I/R, C57BL/6 mice underwent 30 minutes of vascular clamp-induced occlusion of the
superior mesenteric artery followed by variable reperfusion times. Jejunum
segments and intraluminal contents were analyzed for ceramide, sphingosine and
bacteria using immunohistochemistry. Jejunum samples were also homogenized and
cultured to quantify bacterial presence in the proximal intestine. RESULTS: We
hypothesized that I/R induces an increase of ceramide in the intestine resulting
in increased permeability, while a concomitant decrease of sphingosine may permit
bacterial overgrowth. Control mice had no measurable bacteria in their proximal
jejunum as measured by tissue culture and immunohistochemistry. After I/R,
bacterial counts in the jejunum increased in a time-dependent manner, reaching a
peak at 12 hours after reperfusion. Immunohistochemical analysis revealed a
marked increase in ceramide in the vasculature of jejunal villi. In contrast,
while ceramide concentrations in the epithelial cells decreased after I/R,
sphingosine levels appeared to remain unchanged. Surprisingly, bacteria present
in the jejunal lumen following I/R contained a ceramide coat. CONCLUSION: These
data indicate that intestinal I/R leads to small intestine bacterial overgrowth
as well as ceramide formation in the jejunal vasculature, which may contribute to
the gut permeability associated with this injury. Moreover, our novel finding of
ceramide in bacterial membranes represents a new opportunity to investigate the
dynamic pathogenicity of the gut microbiome. The hypothesis that a decrease of
sphingosine after I/R permits bacterial overgrowth in the intestine was not
confirmed.
PMID- 27607917
TI - Enthalpy-Entropy Compensation (EEC) Effect: Decisive Role of Free Energy.
AB - The "enthalpy-entropy compensation" (EEC) effect has been a long-standing
fascinating yet unresolved phenomenon in chemical thermodynamics. The reasons for
the observation of EEC are not clear. Various views such as empirical,
extrathermodynamic, error-related, solvation, and so forth as reasons for the H/S
linear correlation are floating. Statistical reasons and a hidden Carnot's cycle
(involving microscopic "heating and cooling" machines) have also been proposed
recently for the observation of EEC. In this work, we have attempted a different
line of approach to understand and explain the phenomenon. In the EEC treatment,
the enthalpy (DeltaH) and entropy (DeltaS) values of "similar processes" are
considered keeping aside the role of the other important thermodynamic parameter,
that is, the free energy (DeltaG). Considering DeltaG along with DeltaH and
DeltaS, it is established that the conventional EEC plot is not appropriate and
mathematically sound. Consideration of DeltaG may account for correlations of
different kinds, linear, nonlinear, and so forth. Reports of non- or
anticompensation phenomenon also prevail in the literature. A realistic account
of the role of DeltaG along with DeltaH and DeltaS in the understanding of such
EEC correlations using authentic literature data is presented and discussed
herein. EEC has several facets. Planned studies on similar systems with a wide
range of DeltaG values are required for realistic evaluation of the EEC and
antienthalpy entropy compensation manifestations.
PMID- 27607916
TI - Taxonomic confirmation of mud crab species (genus Scylla) in Bangladesh by
nuclear and mitochondrial DNA markers.
AB - Taxonomy of mud crabs genus Scylla has been misidentified for several years due
to their high morphological plasticity. Several reports concerning mud crab have
been published with misleading identification in Bangladesh. In this study,
partial fragments of nuclear and mitochondrial DNA of Scylla species obtained
from four locations along the Bangladesh coast were used to resolve taxonomical
ambiguity of mud crab species. A single PCR product from the nuclear first
internal transcribed spacer (ITS-1) marker and phylogenetic trees constructed
based on 16S rDNA sequences indicated that all Scylla species obtained in this
study were S. olivacea. Both molecular data and morphological characters revealed
that S. olivacea is the only major species in Bangladesh coastal waters. Further,
the 16S rDNA haplotypes significantly differed with known S. serrata by 33%. From
this study it is clear that 'S. serrata' commonly reported from Bangladesh should
be S. olivacea.
PMID- 27607918
TI - Targeting Bacterial Nitric Oxide Synthase with Aminoquinoline-Based Inhibitors.
AB - Nitric oxide is produced in Gram-positive pathogens Bacillus anthracis and
Staphylococcus aureus by the bacterial isoform of nitric oxide synthase (NOS).
Inhibition of bacterial nitric oxide synthase (bNOS) has been identified as a
promising antibacterial strategy for targeting methicillin-resistant S. aureus
[Holden, J. K., et al. (2015) Chem. Biol. 22, 785-779]. One class of NOS
inhibitors that demonstrates antimicrobial efficacy utilizes an aminoquinoline
scaffold. Here we report on a variety of aminoquinolines that target the
bacterial NOS active site, in part, by binding to a hydrophobic patch that is
unique to bNOS. Through mutagenesis and crystallographic studies, our findings
demonstrate that aminoquinolines are an excellent scaffold for further aiding in
the development of bNOS specific inhibitors.
PMID- 27607919
TI - Ungual hyalohyphomycosis caused by Fusarium proliferatum in an immunocompetent
patient.
AB - The patient was a 73-year-old healthy female farmer who had been treated with
terbinafine for 25.5 months by a primary physician. She exhibited a discoloration
and thickening of the right big toenail. She had no concomitant paronychia.
Direct microscopy revealed chlamydoconidia and hyphae, and periodic acid-Schiff
stained nail specimen showed septate hyphae. On the basis of these morphological
features and gene analysis, the final diagnosis was ungual hyalohyphomycosis
caused by Fusarium proliferatum. Topical application of 10% efinaconazole
solution cured the disease in 10 months.
PMID- 27607920
TI - Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.
AB - INTRODUCTION: Hepatitis C virus (HCV) infection affects about 200 million people
worldwide and represents a leading cause of liver-related mortality. Eradication
of HCV infection, achieved mainly through direct-acting antivirals (DAA), results
in a decrease of mortality and an improvement of quality of life. These drugs
have a maximal efficacy and an optimal tolerability. However, their high cost
precludes a universal access even in wealthy countries. Areas covered: This
article deals with the policies adopted for the use of the new anti-HCV drugs,
especially in Europe and most of all in Italy, supposedly the developed country
with the highest HCV prevalence. The literature search was performed using Pubmed
and Web of Science. Moreover, national regulatory institutional websites were
consulted. Expert commentary: The current policy of limitation to the access of
the DAA presents a series of ethical issues that makes it non-applicable. A
'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide
benefits of anti-HCV treatment not only for the advanced stage of infection, but
also for the initial stages. A reduction in price of the drugs is the actual
condition to achieve such a change.
PMID- 27607921
TI - Gold-Nanoparticle-Loaded Carbonate-Modified Titanium(IV) Oxide Surface: Visible
Light-Driven Formation of Hydrogen Peroxide from Oxygen.
AB - Gold nanoparticle-loaded rutile TiO2 with a bimodal size distribution around 10.6
nm and 2.3 nm (BM-Au/TiO2 ) was prepared by the deposition precipitation and
chemical reduction (DP-CR) technique. Visible-light irradiation (lambda>430 nm)
of the BM-Au/TiO2 plasmonic photocatalyst yields 35 MUm H2 O2 in aerated pure
water at irradiation time (tp )=1 h, and the H2 O2 concentration increases to
640+/-60 MUm by the addition of 4 % HCOOH as a sacrificing electron donor.
Further, a carbonate-modified surface BM-Au/TiO2 (BM-Au/TiO2 -CO3 (2-) )
generates a millimolar level of H2 O2 at tp =1 h with a quantum efficiency (Phi)
of 5.4 % at lambda=530 nm under the same conditions. The recycle experiments
confirmed the stable performance of BM-Au/TiO2 .
PMID- 27607927
TI - Effects of oxytetracycline on the performance and activity of biomixtures:
Removal of herbicides and mineralization of chlorpyrifos.
AB - Biopurification systems (BPS) are design to remove pesticides from agricultural
wastewater. This work assays for the first time the potential effect of an
antibiotic of agricultural use (oxytetracycline, OTC) on the performance of a
biomixture (biologically active core of BPS), considering that antibiotic
containing wastewaters are also produced in agricultural labors. The respiration
of the biomixture was stimulated in the presence of increasing doses of OTC
(>=100mgkg-1), and only slightly increased with lower doses (<=10mgkg-1). When co
applied during the removal of chlorpyrifos, OTC increased chlorpyrifos
mineralization rates at low doses, resembling a hormetic effect. The biomixture
was also able to remove three herbicides (atrazine, ametryn and linuron) with
half-lives of 24.3 d, 43.9 d and 30.7 d; during co-application of OTC at a
biomixture-relevant concentration, only the removal of ametryn was significantly
inhibited, increasing its half-life to 92.4 d. Ecotoxicological assays revealed
that detoxification takes place in the biomixture during the removal of
herbicides in the presence of OTC. Overall results suggest that co-application of
OTC in a biomixture does not negatively affect the performance of the matrix in
every case; moreover, the co-application of this antibiotic could improve the
mineralization of some pesticides.
PMID- 27607928
TI - Physiology and bioprocess of single cell of Stenotrophomonas maltophilia in
bioremediation of co-existed benzo[a]pyrene and copper.
AB - Polycyclic aromatic hydrocarbons (PAHs) and heavy metals are generally present in
mixtures in the e-waste dismantling areas, posing serious health risk to the
local people. Bioremediation has been considered as a promising approach for PAHs
and heavy metals removal. In this study, we applied flow cytometry to obtain a
better understanding of membrane potential (MP), apoptosis and cell cycle of
Stenotrophomonas maltophilia affected by combined pollutants of
benzo[a]pyrene(BaP) and Cu(II). The results showed that BaP was the main factor
damaging the cell membrane and influencing the MP. S. maltophilia could even
protect against upsetting situation by encouraging early apoptosis, whereby
compromised cells committed suicide, as a result, which, in turn, facilitated the
metabolism of the bacteria with high-vitality. Furthermore, even if the bacterial
cell division was blocked and stopped reproduction, a large number of key enzymes
inside cells could still be used for degradation of BaP. The expression of
protein related to the transport and metabolism of BaP, regulation of redox
reactions and phosphorylation in bacterial cell during bioprocess were evident
different.
PMID- 27607929
TI - Application of vacuum reduction and chlorinated distillation to enrich and
prepare pure germanium from coal fly ash.
AB - Germanium, as strategic reserve metal, plays critical role in high-tech industry.
However, a contradiction of increasing consumption and scarcity of germanium
resource is becoming more and more prominent. This paper proposed an integrated
process to recycle germanium from coal fly ash. This technological process mainly
consisted of two procedures: vacuum reduction with the purposes of enriching
germanium and chlorinated distillation with the purposes of purifying germanium.
Several highlights are summarized as follows: (i) Separation principle and
reaction mechanism were discussed to understand this integrated process. (ii)
Optimum designs and product analysis were developed to guide industrial
recycling. The appropriate parameters for vacuum reduction process on the basis
of response surface methodology (RSM) were 920.53 degrees C and 259.63Pa, with
16.64wt.% reductant, and for the chlorinated distillation process, adding 8mol/l
HCl and L/S 7, 8wt.% MnO2. The global recovery rate of germanium was 83.48+/
0.36% for the integrated process. (iii) This process overcomes the shortages of
traditional process and shows its efficiency and environmental performance. It is
significant in accordance with the "Reduce, Reuse and Recycle Principle" for
solid waste and further provides a new opportunity for germanium recovery from
waste by environment-friendly way.
PMID- 27607930
TI - Formation of iodo-trihalomethanes, iodo-acetic acids, and iodo-acetamides during
chloramination of iodide-containing waters: Factors influencing formation and
reaction pathways.
AB - This study investigated systematically the factors influencing the formation of
iodinated disinfection by-products (I-DBPs) during chloramination of I-
containing waters, including reaction time, NH2Cl dose, I- concentration, pH,
natural organic matter (NOM) concentration, Br-/I- molar ratio, and water matrix.
Among the I-DBPs detected, iodoform (CHI3), iodoacetic acid (IAA), diiodoacetic
acid (DIAA), triiodoacetic acid (TIAA), and diiodoacetamide (DIAcAm) were the
major species produced from reactions between reactive iodine species (HOI/I2)
and NOM. A kinetic model involving the reactions of NH2Cl auto-decomposition,
iodine species transformation and NOM consumption was developed, which could well
describe NH2Cl decay and HOI/I2 evolution. Higher concentrations of CHI3, IAA,
DIAA, TIAA, and DIAcAm were observed in chloramination than in chlorination,
whereas IO3- was only formed significantly in chlorination. Maximum formation of
I-DBPs occurred at pH 8.0, but acidic conditions favored the formation of
iodinated haloacetic acids and DIAcAm. Increasing Br-/I- molar ratio from 1 to 10
did not increase the total amount of I-DBPs, but produced more bromine
substituting species. In addition, chloramination of 18 model compounds indicated
that low-SUVA254 (specific ultraviolet absorbance at 254nm) NOM generally favored
the formation of I-DBPs compared to high-SUVA254 NOM. Finally, potential pathways
for I-DBPs formation from chloramination of NOM were proposed.
PMID- 27607931
TI - Toxicity mechanisms and synergies of silver nanoparticles in 2,4-dichlorophenol
degradation by Phanerochaete chrysosporium.
AB - Mechanisms of silver nanoparticles-mediated toxicity to Phanerochaete
chrysosporium and the influence of silver nanoparticles (AgNPs) on the
biodegradation of 2,4-dichlorophenol (2,4-DCP) have been systematically
investigated. AgNPs at low doses (0-60MUM) have greatly enhanced the degradation
ability of P. chrysosporium to 2,4-DCP with the maximum degradation rates of more
than 94%, exhibiting excellent synergies between AgNPs and P. chrysosporium in
the degradation of 2,4-DCP. Meanwhile, removal of total Ag was also at high
levels and highly pH dependent. However, significant inhibition was highlighted
on 2,4-DCP biodegradation and Ag removal upon treatment with AgNPs at high doses
and AgNO3 at low-level exposure. Results also suggested that AgNPs-induced
cytotoxicity could arise from the "Trojan-horse" mechanism executing particle
effects, ion effects, or both, ruling out extracellularly released Ag+. Moreover,
under relatively low concentrations of AgNPs exposure, 2,4-DCP was broken into
linear chain organics, and eventually turned into CO2 and H2O through reductive
dechlorination and reaction with hydroxyl radicals. FTIR analysis showed that
amino, carboxyl, carbonyl, and sulfur-containing functional groups played crucial
roles in Ag transportation and the reduction of Ag+ to Ag0.
PMID- 27607932
TI - Application of nanoscale zero valent iron and iron powder during sludge anaerobic
digestion: Impact on methane yield and pharmaceutical and personal care products
degradation.
AB - Lab scale and single stage high solid anaerobic digestion of sewage sludge spiked
with freshly synthesized nanoscale zero valent iron (nZVI) and commercial iron
powder (IP) under mesophilic condition (37+/-1 degrees C) was performed. The
effects of both additives on methane yield, and pharmaceutical and personal care
product (PPCP) removal were investigated. Results showed that methane yield was
increased by 25.2% and 40.8% in the presence of nZVI (0.1%) and IP (1.6%),
respectively. Removal efficiencies of chemical oxygen demand were 54.4% and 66.2%
in the presence of nZVI and IP, respectively, which were higher compared to the
control group (44.6%). In addition, most PPCPs could be partly or completely
removed during the anaerobic digestion process. The application of nZVI and IP
showed positive impact on the removal of chlorinated PPCPs (p<0.05), but did not
show significant impact on other PPCPs (p>0.05). Our finding suggests that the
application of nZVI and IP in anaerobic digestion could be a promising way to
enhance methane yield but had less improvement on PPCP degradation.
PMID- 27607933
TI - Removal of polychlorinated biphenyl congeners in mixture Delor 103 from
wastewater by ozonation vs/and biological method.
AB - Polychlorinated biphenyls (PCBs) produced in Slovakia as a commercial mixture
Delor 103 cause the main contamination of sediment, water and fish in the eastern
part of Slovakia. Delor 103 is a mixture of 40% PCB congeners, nine of them: PCB
8 (2,4'-dichlorobiphenyl), PCB 28 (2,4,4'-trichlorobiphenyl), PCB 52 (2,2',5,5'
tetrachlorobiphenyl), PCB 101 (2,2',4,5,5'-pentachlorobiphenyl), PCB 118
(2,3',4,4',5-pentachlorobiphenyl), PCB 138 (2,2',3,4,4',5'-hexachlorobiphenyl),
PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), PCB 180 (2,2',3,4,4',5,5'
heptachlorobiphenyl), and PCB 203 (2,2',3,4,4',5,5',6-octachlorobiphenyl), were
monitored for their removal by ozonation and biodegradation using Achromobacter
xylosoxidans. Ozonation improved the removal of PCB 52, 118, 153, 138, 180, and
203 using biological method with A. xylosoxidans. Degradation of 55% of the total
amount of nine selected PCB congeners was achieved by the biological method with
A. xylosoxidans, while 86% of the total amount of the nine selected PCB congeners
were removed by the ozonation method; using a combination of biological and
chemical methods, ozonation and A. xylosoxidans, showed a 94% removal efficiency
of the selected PCB congeners present in mixture Delor 103.
PMID- 27607935
TI - Dissipative rogue waves induced by soliton explosions in an ultrafast fiber
laser.
AB - We reported on the observation of dissipative rogue waves (DRWs) induced by
soliton explosions in an ultrafast fiber laser. It was found that the soliton
explosions could be obtained in the fiber laser at a critical pump power level.
During the process of the soliton explosion, the high-amplitude waves that
fulfill the rogue wave criteria could be detected. The appearance of the DRWs was
identified by characterizing the intensity statistics of the time-stretched
soliton profile based on the dispersive Fourier-transform method. Our findings
provide the first experimental demonstration that the DRWs could be observed in
the soliton explosion regime and further enhance the understanding of the
physical mechanism of optical RW generation.
PMID- 27607936
TI - Frequency locking of a field-widened Michelson interferometer based on optimal
multi-harmonics heterodyning.
AB - A general resonant frequency locking scheme for a field-widened Michelson
interferometer (FWMI), which is intended as a spectral discriminator in a high
spectral-resolution lidar, is proposed based on optimal multi-harmonics
heterodyning. By transferring the energy of a reference laser to multi-harmonics
of different orders generated by optimal electro-optic phase modulation, the
heterodyne signal of these multi-harmonics through the FWMI can reveal the
resonant frequency drift of the interferometer very sensitively within a large
frequency range. This approach can overcome the locking difficulty induced by the
low finesse of the FWMI, thus contributing to excellent locking accuracy and lock
acquisition range without any constraint on the interferometer itself. The
theoretical and experimental results are presented to verify the performance of
this scheme.
PMID- 27607937
TI - Full-field spatially incoherent illumination interferometry: a spatial resolution
almost insensitive to aberrations.
AB - We show that with spatially incoherent illumination, the point spread function
(PSF) width/spatial resolution of an imaging interferometer like that used in
full-field optical coherence tomography (OCT) is almost insensitive to
aberrations. In these systems, aberrations mostly induce a reduction of the
signal level that leads to a loss of the signal-to-noise ratio without broadening
the system PSF. This is demonstrated by comparison with traditional scanning OCT
and wide-field OCT with spatially coherent illuminations. Theoretical analysis
and numerical calculation as well as experimental results are provided to show
this specific merit of incoherent illumination in full-field OCT. To the best of
our knowledge, this is the first time that such a result has been demonstrated.
PMID- 27607934
TI - Chemically treated carbon black waste and its potential applications.
AB - In this work, carbon black waste - a hazardous solid residue generated from
gasification of crude oil bottom in refineries - was successfully used for making
an absorbent material. However, since the carbon black waste also contains
significant amounts of heavy metals (especially nickel and vanadium), chemical
leaching was first used to remove these hazardous impurities from the carbon
black waste. Acid leaching with nitric acid was found to be a very effective
method for removal of both nickel and vanadium from the carbon black waste (i.e.
up to 95% nickel and 98% vanadium were removed via treatment with 2M nitric acid
for 1h at 20 degrees C), whereas alkali leaching by using NaOH under the same
condition was not effective for removal of nickel (less than 10% nickel was
removed). Human lung cells (MRC-5) were then used to investigate the toxicity of
the carbon black waste before and after leaching. Cell viability analysis showed
that the leachate from the original carbon black waste has very high toxicity,
whereas the leachate from the treated samples has no significant toxicity.
Finally, the efficacy of the carbon black waste treated with HNO3 as an absorbent
for dye removal was investigated. This treated carbon black waste has high
adsorption capacity (~361.2mg dye/g carbonblack), which can be attributed to its
high specific surface area (~559m2/g). The treated carbon black waste with its
high adsorption capacity and lack of cytotoxicity is a promising adsorbent
material. Moreover, the carbon black waste was found to show high electrical
conductivity (ca. 10S/cm), making it a potentially valuable source of conductive
material.
PMID- 27607938
TI - Measurements of the nonlinear refractive index of air, N2, and
O2 at 10 MUm using four-wave mixing.
AB - We report on measurements of the nonlinear index of refraction of air,
N2, and O2 at a wavelength close to 10 MUm by collinear
four-wave mixing of a 200 MW CO2 laser beat-wave. The use of a 200 ps
long beat-wave comprising radiation amplified on the 10P20 and 10R16 lines of the
CO2 laser provides a sensitive method to measure the small
nonlinearities characteristic of the gas phase in a spectral region where no such
data exists.
PMID- 27607939
TI - Locally deformed-ring hybrid microlasers exhibiting stable unidirectional
emission from a Si waveguide.
AB - We propose and demonstrate a locally deformed-ring (LDR) hybrid microlaser to
realize stable unidirectional emission from a silicon waveguide. The coupled
modes eliminate the competition between clockwise (CW) and counter-clockwise
(CCW) modes, and the highly unidirectional characteristics are achieved with an
enhanced mode quality factor based on a locally deformed notch in the LDR
resonator. Using a divinylsiloxane-benzocyclobutene bonding technique, a LDR
hybrid microlaser is fabricated vertically coupled to a silicon waveguide with a
radius of 20 MUm, a ring width of 4 MUm and a notch width of 500 nm. The
threshold current is 7 mA, and single-mode lasing is achieved with the side-mode
suppression ratio of 27 dB. Nearly total unidirectional output from the CCW
direction of a Si waveguide is demonstrated with a unidirectional ratio of 0.053.
PMID- 27607940
TI - Surpassing the shot-noise limit by homodyne-mediated feedback.
AB - Entangled systems with large quantum Fisher information (QFI) can be used to
outperform the standard quantum limit of the separable systems in quantum
metrology. However, the interaction between the system and the environments
inevitably leads to decoherence and decrease of the QFI, and it is not clear
whether the entanglement systems can be a better resource than separable systems
in the realistic physical condition. In this work, we study the steady QFI of two
driven and collectively damped qubits with homodyne-mediated feedback. We show
that the steady QFI can be significantly enhanced both in the cases of symmetric
feedback and nonsymmetric feedback, and the shot-noise limit of separable states
can be surpassed in both cases. The QFI can even achieve the Heisenberg limit for
appropriate feedback parameters and initial conditions in the case of symmetric
feedback. We also show that an initial-condition-independent steady QFI can be
obtained by using nonsymmetric feedback.
PMID- 27607941
TI - Dispersion of nonlinear refractive index in layered WS2 and
WSe2 semiconductor films induced by two-photon absorption.
AB - Both the nonlinear absorption and nonlinear refraction properties of
WS2 and WSe2 semiconductor films have been characterized by
using Z-scan technique with femtosecond pulses at the wavelength of 1040 nm. It
is found that these films have two-photon absorption response with the nonlinear
absorption coefficient of ~103 cm GW-1, and a dispersion
of nonlinear refractive index in the WS2 films that translated from
positive in the monolayer to negative in bulk materials.
PMID- 27607942
TI - All-polymer arrayed waveguide grating at 850 nm: design, fabrication, and
characterization.
AB - In this Letter, a novel all-polymer arrayed waveguide grating (AWG) device with
an operating wavelength around 850 nm is reported. The all-polymer AWG consists
of polymer ridge waveguides fabricated on a thin poly(methyl methacrylate) foil
via microscope projection photolithography. The developed device is suitable to
be integrated into optical circuits, e.g., a planar polymer foil and, along with
other optical integrated devices, to be used for different sensing applications.
The functionality of the device is demonstrated by using a fiber Bragg grating
sensor and performing strain measurements.
PMID- 27607943
TI - Hybrid averaging offers high-flow contrast by cost apportionment among imaging
time, axial, and lateral resolution in optical coherence tomography angiography.
AB - The current temporal, wavelength, angular, and spatial averaging approaches trade
imaging time and resolution for multiple independent measurements that improve
the flow contrast in optical coherence tomography angiography (OCTA). We find
that these averaging approaches are equivalent in principle, offering almost the
same flow contrast enhancement as the number of averages increases. Based on this
finding, we propose a hybrid averaging strategy for contrast enhancement by cost
apportionment. We demonstrate that, compared with any individual approach, the
hybrid averaging is able to offer a desired flow contrast without severe
degradation of imaging time and resolution. Making use of the extended range of a
VCSEL-based swept-source OCT, an angular averaging approach by path length
encoding is also demonstrated for flow contrast enhancement.
PMID- 27607944
TI - Scattering robust 3D reconstruction via polarized transient imaging.
AB - Reconstructing 3D structure of scenes in the scattering medium is a challenging
task with great research value. Existing techniques often impose strong
assumptions on the scattering behaviors and are of limited performance. Recently,
a low-cost transient imaging system has provided a feasible way to resolve the
scene depth, by detecting the reflection instant on the time profile of a surface
point. However, in cases with scattering medium, the rays are both reflected and
scattered during transmission, and the depth calculated from the time profile
largely deviates from the true value. To handle this problem, we used the
different polarization behaviors of the reflection and scattering components, and
introduced active polarization to separate the reflection component to estimate
the scattering robust depth. Our experiments have demonstrated that our approach
can accurately reconstruct the 3D structure underlying the scattering medium.
PMID- 27607945
TI - Efficient 2122 nm Ho:YAG laser intra-cavity pumped by a narrowband-diode-pumped
Tm:YAG laser.
AB - We first demonstrate an efficient Ho:YAG laser intra-cavity pumped by a
narrowband-diode-pumped Tm:YAG laser. The pump wavelength of the laser diode was
selected according to the excitation peak which is also one of the absorption
peaks of a 3.5 at. % Tm:YAG crystal and was locked by volume Bragg gratings. In
the Tm laser experiment, a maximum output power of 11.12 W, corresponding to a
slope efficiency of 51.6%, was obtained. In the Ho laser experiment, a maximum
output power of 8.03 W at 2122 nm with a slope efficiency of 38% was obtained for
24.96 W of diode pump power incident on the Tm:YAG rod.
PMID- 27607946
TI - Compact optical true time delay beamformer for a 2D phased array antenna using
tunable dispersive elements.
AB - A hardware-compressive optical true time delay architecture for 2D beam steering
in a planar phased array antenna is proposed using fiber-Bragg-grating-based
tunable dispersive elements (TDEs). For an M*N array, the proposed system
utilizes N TDEs and M wavelength-fixed optical carriers to control the time
delays. Both azimuth and elevation beam steering are realized by programming the
settings of the TDEs. An experiment is carried out to demonstrate the delay
controlling in a 2*2 array, which is fed by a wideband pulsed signal. Radiation
patterns calculated from the experimentally measured waveforms at the four
antennas match well with the theoretical results.
PMID- 27607947
TI - Lock-in-detection-free line-scan stimulated Raman scattering microscopy for near
video-rate Raman imaging.
AB - We report on the development of a unique lock-in-detection-free line-scan
stimulated Raman scattering microscopy technique based on a linear detector with
a large full well capacity controlled by a field-programmable gate array (FPGA)
for near video-rate Raman imaging. With the use of parallel excitation and
detection scheme, the line-scan SRS imaging at 20 frames per second can be
acquired with a ~5-fold lower excitation power density, compared to conventional
point-scan SRS imaging. The rapid data communication between the FPGA and the
linear detector allows a high line-scanning rate to boost the SRS imaging speed
without the need for lock-in detection. We demonstrate this lock-in-detection
free line-scan SRS imaging technique using the 0.5 MUm polystyrene and 1.0 MUm
poly(methyl methacrylate) beads mixed in water, as well as living gastric cancer
cells.
PMID- 27607948
TI - Beam combinable, kilowatt, all-fiber amplifier based on phase-modulated laser
gain competition.
AB - We report power scaling results of a highly efficient narrow-linewidth monolithic
Yb-doped fiber amplifier seeded with two signals, operating at 1038 and 1064 nm.
With the appropriate seed power ratio applied, this technique was shown to
suppress stimulated Brillouin scattering in conjunction with phase modulation,
while generating the output power in predominantly the longer wavelength signal.
Notably, the integration of laser gain competition with pseudo-random bit
sequence phase modulation, set at a clock rate of 2.5 GHz and utilizing an
optimized pattern to match the shortened effective nonlinear length, yielded 1 kW
of output power. The beam quality was measured to be near the diffraction limit
with no sign of transverse mode instability. Furthermore, the coherent beam
combination performance of the amplifier provided a 90% combining efficiency with
no indication of spectral broadening when compared to the single-tone case.
Overall, the power scaling results represent a significant reduction in spectral
linewidth compared to that of commercially available narrow-linewidth Yb-doped
fiber amplifiers.
PMID- 27607949
TI - Duobinary pulse shaping for frequency chirp enabled complex modulation.
AB - The frequency chirp of optical direct modulation (DM) used to be a performance
barrier of optical transmission system, because it broadens the signal optical
spectrum, which becomes more susceptible to chromatic dispersion induced inter
symbol interference (ISI). However, by considering the chirp as frequency
modulation, the single DM simultaneously generates a 2-D signal containing the
intensity and phase (namely, the time integral of frequency). This complex
modulation concept significantly increases the optical signal to noise ratio
(OSNR) sensitivity of DM systems. This Letter studies the duobinary pulse shaping
(DB-PS) for chirp enabled DM and its impact on the optical bandwidth and system
OSNR sensitivity. DB-PS relieves the bandwidth requirement, at the sacrifice of
system OSNR sensitivity. As DB-PS induces a controlled ISI, the receiver requires
one more tap for maximum likelihood sequence estimation (MLSE). We verify this
modified MLSE with a 10-Gbaud duobinary PAM-4 transmission experiment.
PMID- 27607950
TI - Bragg-Berry mirrors: reflective broadband q-plates.
AB - We report on the experimental realization of flat mirrors enabling the broadband
generation of optical vortices upon reflection. The effect is based on the
geometric Berry phase associated with the circular Bragg reflection phenomenon
from chiral uniaxial media. We show the reflective optical vortex generation from
both diffractive and nondiffractive paraxial light beams using spatially
patterned chiral liquid crystal films. The intrinsic spectrally broadband
character of spin-orbit generation of optical phase singularities is demonstrated
over the full visible domain. Our results do not rely on any birefringent
retardation requirement and, consequently, foster the development of a novel
generation of robust optical elements for spin-orbit photonic technologies.
PMID- 27607951
TI - Three-wave mixing of ordinary and backward electromagnetic waves: extraordinary
transients in the nonlinear reflectivity and parametric amplification.
AB - Three-wave mixing of ordinary and backward electromagnetic waves in a pulsed
regime is investigated in the metamaterials that enable the coexistence and phase
matching of such waves. It is shown that the opposite direction of phase velocity
and energy flux in backward waves gives rise to extraordinary transient processes
due to greatly enhanced optical parametric amplification and frequency up- and
down-shifting nonlinear reflectivity. The differences are illustrated through
comparison with the counterparts in ordinary, co-propagating settings.
PMID- 27607952
TI - Generation of a frequency comb spanning more than 3.6 octaves from ultraviolet to
mid infrared.
AB - We have observed an ultra-broadband frequency comb with a wavelength range of at
least 0.35 to 4.4 MUm in a ridge-waveguide-type periodically poled lithium
niobate device. The PPLN waveguide is pumped by a 1.0-2.4 MUm wide frequency comb
with an average power of 120 mW generated using an erbium-based mode-locked fiber
laser and a following highly nonlinear fiber. The coherence of the extended comb
is confirmed in both the visible (around 633 nm) and the mid-infrared regions.
PMID- 27607953
TI - High-efficiency red electroluminescent device based on multishelled InP quantum
dots.
AB - We report on the synthesis of highly fluorescent red-emitting InP quantum dots
(QDs) and their application to the fabrication of a high-efficiency QD-light
emitting diode (QLED). The core/shell heterostructure of the QDs is elaborately
tailored toward a multishelled structure with a composition-gradient ZnSeS
intermediate shell and an outer ZnS shell. Using the resulting InP/ZnSeS/ZnS QDs
as an emitting layer, all-solution-processible red InP QLEDs are fabricated with
a hybrid multilayered device structure having an organic hole transport layer
(HTL) and an inorganic ZnO nanoparticle electron transport layer. Two HTLs of
poly(9-vinlycarbazole) or poly[(9,9-dioctylfluorenyl-2,7-diyl)-co
(4,4'-(N-(4-sec-butylphenyl))diphenyl-amine), whose hole mobilities
are different by at least three orders of magnitude, are individually applied for
QLED fabrication and such HTL-dependent device performances are compared. Our
best red device displays exceptional figures of merit such as a maximum luminance
of 2849 cd/m2, a current efficiency of 4.2 cd/A, and an external
quantum efficiency of 2.5%.
PMID- 27607954
TI - Experimental demonstration of a 10 Gb/s non-orthogonal multi-dimensional CAP-PON
system based on the ISI and CCI cancellation algorithm.
AB - The concept of a multi-dimensional carrierless amplitude and phase modulation
(CAP) passive optical network (PON) system based on non-orthogonal transceiver
filters is presented for the first time, to the best of our knowledge, to improve
the spectral efficiency (SE). To eliminate the interferences caused by the non
orthogonal transceiver filters, a novel inter-symbol interference (ISI) and cross
channel interference (CCI) cancellation algorithm (ICCA) is proposed. In our
experiment, a 10 Gb/s four-dimensional with four levels/dimension and non
orthogonal CAP data transmission is successfully demonstrated over a 20 km
standard single mode fiber. The results indicate that a SE gain from 3.85 to 4.35
bit/s/Hz is achieved by the combination of the proposed ICCA with the traditional
modified cascaded multi-modulus and decision-directed least mean square
algorithm.
PMID- 27607955
TI - Decoupled polarization dynamics of incoherent waves and bimodal spectral
incoherent solitons.
AB - We consider the propagation of strongly incoherent waves in optical fibers in the
framework of the vector nonlinear Schrodinger equation (VNLSE) accounting for the
Raman effect. On the basis of the wave turbulence theory, we derive a kinetic
equation that greatly simplifies the VNLSE and provides deep physical insight
into incoherent wave dynamics. When applied to the study of polarization effects,
the theory unexpectedly reveals that the linear polarization components of the
incoherent wave evolve independently from each other, even in the presence of
weak fiber birefringence. When applied to light propagation in bimodal fibers,
the theory reveals that the incoherent modal components can be strongly coupled.
After a complex transient, the modal components self-organize into a vector
spectral incoherent soliton: The two solitons self-trap and propagate with a
common velocity in frequency space.
PMID- 27607956
TI - Low-loss high-confinement waveguides and microring resonators in AlGaAs-on
insulator.
AB - AlGaAs is a promising material for integrated nonlinear photonics due to its
intrinsic high nonlinearity. However, the challenging fabrication of deep etched
AlGaAs devices makes it difficult to realize high-performance devices such as low
loss dispersion engineered waveguides and high-quality microring resonators.
Here, we report a process to make high-quality AlGaAs-on-insulator (AlGaAsOI)
wafers where high confinement waveguides can be realized. Using optimized
patterning processes, we fabricated AlGaAsOI waveguides with propagation losses
as low as 1 dB/cm and microring resonators with quality factors up to 350,000 at
telecom wavelengths. Our demonstration opens new prospects for AlGaAs devices in
integrated nonlinear photonics.
PMID- 27607957
TI - Periodic density modulation for quasi-phase-matching of optical frequency
conversion is inefficient under shallow focusing and constant ambient pressure.
AB - The two main mechanisms of a periodic density modulation relevant to nonlinear
optical conversion in a gas medium are spatial modulations of the index of
refraction and of the number of emitters. For a one-dimensional model neglecting
focusing and using a constant ambient pressure, it is shown theoretically and
demonstrated numerically that the effects of these two mechanisms during
frequency conversion cancel each other exactly. Under the considered conditions,
this makes density modulation inefficient for quasi-phase-matching an optical
frequency conversion process. This result is particularly relevant for high-order
harmonic generation.
PMID- 27607958
TI - Linearly polarized single TM mode terahertz waveguide.
AB - We design a hollow-core terahertz (THz) waveguide guiding a single linearly
polarized mode. This is achieved using a hybrid cladding, where we introduce a
ring of subwavelength structures, including metal wires and air-holes. The wire
based cladding is extremely anisotropic, reflecting only transverse magnetic (TM)
modes. The polarization of TM modes is further manipulated by replacing some
wires with air-holes. Numerical simulations confirm the guidance of only an x
polarized TM2 mode over 0.36-0.46 THz in a wavelength-scale core
(diameter of 1 mm). The propagation losses are of the order 0.25 dB/cm, with low
bend losses <0.3 dB/cm at 0.4 THz for a bend radius of 5 cm.
PMID- 27607959
TI - Utilizing the Kantorovich metric for the validation of optical turbulence
predictions.
AB - In this Letter, via idealized and realistic case studies, we have documented the
limitations of several conventional metrics in validating Cn2 profile
predictions. We have introduced the (normalized) Kantorovich metric as a viable
alternative and demonstrated its prowess.
PMID- 27607960
TI - Differential interference contrast imaging using a pair of twisted nematic cells.
AB - Nematic liquid crystal behaves like an optically uniaxial crystal whose optical
axis coincides with the direction of molecular orientation. When an electric
field is applied, a lateral shear of incident light is induced, depending on the
angle of molecular inclination. While this may degrade the image quality for
display applications, the precise electrical tunability of the lateral shear
distance is desirable for differential interference contrast (DIC) imaging. In
this Letter, a pair of twisted nematic (TN) cells is used for DIC imaging instead
of the normal DIC prisms, and the unique optical properties of the TN cell are
investigated for DIC imaging applications.
PMID- 27607961
TI - Si-prism-array coupled terahertz-wave parametric oscillator with pump light
totally reflected at the terahertz-wave exit surface.
AB - A Si-prism-array coupled terahertz (THz)-wave parametric oscillator with the pump
totally reflected at the THz-wave exit surface (PR-Si-TPO) is demonstrated by
manufacturing an 800 nm air gap between the crystal and the Si-prism array.
Influence on the total reflection of the pump from the Si prisms is eliminated
and efficient coupling of the THz wave is ensured by using this air gap. When the
THz-wave frequency varies from 1.8 to 2.3 THz, compared with a Si-prism-array
coupled TPO (Si-TPO) with the pump transmitting through the crystal directly, the
THz-wave output energy is enhanced by 20-50 times, and the oscillating threshold
is reduced by 10%-35%. Furthermore, the high end of the THz-wave frequency tuning
range of the PR-Si-TPO is expanded to 3.66 THz compared with 2.5 THz for the Si
TPO.
PMID- 27607962
TI - Hybrid plasmonic waveguide-based ultra-low insertion loss transverse electric
pass polarizer.
AB - We have designed and experimentally demonstrated an integrated transverse
electric (TE)-pass polarizer on silicon-on-insulator platform. The polarizer
consists of an asymmetric coupling section where only the transverse magnetic
(TM) mode is coupled to the cross-hybrid plasmonic waveguide and attenuated. The
TE mode does not couple and passes through the polarizer. The polarizer was
fabricated on the silicon-on-insulator platform. The device is 30 MUm long, has a
high extinction ratio of more than 28 dB over 150 nm bandwidth, and has a good
fabrication tolerance. Most important, the proposed polarizer has an ultra-low
insertion loss of less than 0.04 dB for the TE mode.
PMID- 27607963
TI - Filtering for unwrapping noisy Doppler optical coherence tomography images for
extended microscopic fluid velocity measurement range.
AB - In this Letter, we report the first application of two phase denoising algorithms
to Doppler optical coherence tomography (DOCT) velocity maps. When combined with
unwrapping algorithms, significantly extended fluid velocity dynamic range is
achieved. Instead of the physical upper bound, the fluid velocity dynamic range
is now limited by noise level. We show comparisons between physical simulated
ideal velocity maps and the experimental results of both algorithms. We
demonstrate unwrapped DOCT velocity maps having a peak velocity nearly 10 times
the theoretical measurement range.
PMID- 27607964
TI - 1 MW peak-power subpicosecond optical pulse source based on a gain-switched
laser diode.
AB - We have generated optical pulses of 1.2 MW peak power and 0.6 ps duration using a
1060 nm band gain-switched laser diode pulse oscillator. Optical pulses are
amplified by three-stage ytterbium-doped fiber amplifiers, and remarkable
reductions of amplified spontaneous emission noise and temporal duration have
been accomplished based on self-phase modulation in the middle-stage amplifier.
After the main amplifier, optical pulses were temporally compressed by a grating
pair, and this enabled generation of subpicosecond optical pulses with over 1 MW
peak power.
PMID- 27607965
TI - Estimation of optical rotation of chiral molecules with weak measurements.
AB - From its beginning, the measurement of optical rotation (OR) is crucial for the
analysis of chiral molecules in many fields. However, the precision measurement
of a weak OR signal with conventional setup remains elusive. In this Letter, we
experimentally propose a precision method to determine the OR of glucose and
fructose based on weak measurements. By using the spin Hall effect of light
(SHEL) as a probe, a nonlinear weak measurements model is established that is
applicable beyond the Aharonov-Albert-Vaidman (AAV) limit. Due to the high
sensitivity of weak measurements amplification with respect to the OR, a
tremendous variation of the amplified beam displacement of the SHEL is observed,
while the concentration of glucose and fructose is slightly changed.
PMID- 27607966
TI - Detection of microscopic defects in optical fiber coatings using angle-resolved
skew rays.
AB - Microscopic defects in optical fiber coatings can be an impending catastrophe for
high-power fiber laser and telecommunications systems and are difficult to detect
with conventional methods. We demonstrate a highly sensitive interrogation
technique that can readily identify faults such as microscopic nicks, scrapes,
low-quality recoatings, and internal defects in fibers and their coatings, based
on skew ray excitation and angle-resolved analysis.
PMID- 27607967
TI - High-power and low-intensity noise laser at 1064 nm.
AB - We have developed a single-frequency, narrow-linewidth (Deltanu<50 kHz) laser
operating at 1064 nm with a high output power (50 W). The laser is based on an
ytterbium-doped fiber master oscillator power amplifier architecture with an
output beam at the diffraction limit. An output power of 50 W is obtained with
two amplification stages using a 50 mW diode laser seeder. We have carefully
studied the relative intensity noise at each amplification stage. The detrimental
effect due to stimulated Brillouin scattering on residual amplitude noise has
been observed on the high-power booster stage. After careful optimization, this
laser exhibits low intensity noise with a RMS value equal to 0.012% (1 kHz/10
MHz) at 50 W.
PMID- 27607968
TI - General formalism for partial spatial coherence in reflection Mueller matrix
polarimetry.
AB - Starting from the first principles, we derive the expressions governing partially
coherent Mueller matrix reflection polarimetry on spatially inhomogeneous
samples. These are reported both in their general form and in the practically
important specific form for two juxtaposed media.
PMID- 27607969
TI - Behavior of femtosecond laser-induced eccentric fiber Bragg gratings at very high
temperatures.
AB - In this work, eccentric Bragg gratings are photoinscribed in telecommunication
grade optical fibers. They are localized close to the core-cladding interface,
yielding strong cladding mode resonance couplings and high photoinduced
birefringence. Their transmitted amplitude spectrum is measured with polarized
light while they are exposed to temperature changes up to 900 degrees C. Despite
the gratings' overall good thermal stability that confirms their robustness for
high-temperature refractometry, we report an interesting polarization effect
depending on both the cladding mode resonance family and mode order. While the
core mode birefringence decreases with growing temperatures, certain cladding
mode resonances show an increase in wavelength splitting between their
orthogonally polarized components. This differential behavior is of high interest
in developing high-resolution, multiparametric sensing platforms.
PMID- 27607970
TI - Dispersion-compensation-free femtosecond Tm-doped all-fiber laser with a 248 MHz
repetition rate.
AB - In this Letter, we report a dispersion-compensation-free ultrafast thulium-doped
all-fiber laser based on nonlinear polarization evolution (NPE) mode locking,
delivering 330 fs soliton pulses at 1950 nm. A multifunctional hybrid fiberized
device was applied in the oscillator to minimize the physical cavity length to
~80 cm with a total dispersion of -0.045 ps2, enabling a state-of
the-art fundamental mode-locking repetition rate of 248 MHz in an NPE-based
oscillator at ~2 MUm.
PMID- 27607971
TI - Coexistence of harmonic soliton molecules and rectangular noise-like pulses in a
figure-eight fiber laser.
AB - We report the coexistence of high-order harmonic soliton molecules and
rectangular noise-like pulses (NLP) in a figure-eight fiber laser mode-locked by
a nonlinear amplifying loop mirror. The harmonic soliton molecule has a
repetition rate of 936.6 MHz, corresponding to the 466th harmonics of the
fundamental cavity repetition rate, with soliton separation of 16.5 ps.
Meanwhile, the rectangular NLP operates at the fundamental repetition rate. In
addition, these two types of pulses could be generated independently by
manipulating the polarization controllers. The experimental results demonstrate
an interesting operation regime of the fiber laser and contribute to enriching
the dynamics of mode-locked pulses in fiber lasers.
PMID- 27607972
TI - Wide and fast dispersion tuning of a picosecond OPO based on aperiodic quasi
phase matching using an axially chirped volume Bragg grating.
AB - We report on a widely tunable synchronously pumped picosecond optical parametric
oscillator (OPO) combining an aperiodically poled MgO-doped LiNbO3
crystal as a broadband gain medium and an axially chirped volume Bragg grating as
a spectral filtering dispersive element. Translation of the Bragg grating along
the beam axis enables wavelength tuning over 215 nm around 3.82 MUm and provides
spectral narrowing. Rapid continuous tuning over 150 nm in 100 ms is
demonstrated.
PMID- 27607973
TI - Inhibition of multi-filamentation of high-power laser beams.
AB - We experimentally demonstrate the control and complete elimination of multi
filamentation in condensed matter by varying the focusing geometry. In
particular, increasing the input beam power enables the extension of the filament
length without generating multi-filaments up to 1400 times the critical power in
fused silica at an 800 nm wavelength. Furthermore, the generated single filament
exhibits spatial solitary wave behavior.
PMID- 27607974
TI - Secondary wavelength stabilization of unbalanced Michelson interferometers for
the generation of low-jitter pulse trains.
AB - We present a double unbalanced Michelson interferometer producing up to four
output pulses from a single input pulse. The interferometer is stabilized with
the Hansch-Couillaud method using an auxiliary low power continuous wave laser
injected into the interferometer, allowing the stabilization of the temporal
jitter of the output pulses to 0.02 fs. Such stabilized pulse trains would be
suitable for driving multi-pulse laser wakefield accelerators, and the technique
could be extended to include amplification in the arms of the interferometer.
PMID- 27607975
TI - Fast numerical autofocus of multispectral complex fields in digital holographic
microscopy with a criterion based on the phase in the Fourier domain.
AB - The knowledge of the complex amplitude of optical fields, that is, both
quantitative phase and intensity, enables numeric reconstruction along the
optical axis. Nonetheless, a criterion is required for autofocusing. This Letter
presents a robust and rapid refocusing criterion suitable for color
interferometric digital holographic microscopy, and, more generally, for
applications where complex amplitude is known for at least two different
wavelengths. This criterion uses the phase in the Fourier domain, which is
compared among wavelengths. It is applicable whatever the nature of the observed
object: opaque, refractive, or both mixed. The method is validated with simulated
and experimental holograms.
PMID- 27607976
TI - Terahertz continuous wave nonlinear-optical detection without phase-locking
between a source and the detector.
AB - We demonstrate the possibility of nonlinear-optical detection of terahertz (THz)
wave radiation without phase-locking between a source and a detector. Spectrally
resolved room-temperature incoherent nonlinear-optical detection is demonstrated
for 0.22-THz continuous wave (CW) radiation by upconversion using a 100-mW CW
laser in a 15-mm-long Mg:LiNbO3 crystal.
PMID- 27607977
TI - Two-photon tomography using on-chip quantum walks.
AB - We present an approach to quantum tomography based on first expanding a quantum
state across extra degrees of freedom and then exploiting the introduced sparsity
to perform reconstruction. We formulate its application to photonic circuits and
show that measured spatial photon correlations at the output of a specially
tailored discrete-continuous quantum walk can enable full reconstruction of any
two-photon spatially entangled and mixed state at the input. This approach does
not require any tunable elements, so it is well suited for integration with on
chip superconducting photon detectors.
PMID- 27607978
TI - Dynamics of dual-polarization VCSEL-based optical frequency combs under optical
injection locking.
AB - The present experimental work studies the dynamics of dual-polarization optical
frequency combs (OFCs) based on gain switching (GS) vertical-cavity surface
emitting laser (VCSEL) diodes under optical injection locking (OIL). This study
presents two main results. First, we have obtained an overall comb formed by two
orthogonally polarized sub-combs with comparable span and power. The overall comb
shows enhanced optical span and flatness and high coherence between its modes.
The second result is that we have been able to control the polarization state of
the overall comb by tuning the polarization state of the injected light by
locking the same single teeth of the comb. This produces an overall comb with
single polarization that is parallel or orthogonal. These are novel findings that
provide for the development of efficient and compact OFCs based on GS VCSEL
sources with versatile polarization dynamics.
PMID- 27607979
TI - Application of the speckle-based phase retrieval method in reconstructing two
unknown interfering wavefronts.
AB - We numerically demonstrate a novel method to simultaneously reconstruct two
unknown interfering wavefronts. The speckle-based phase retrieval technique is
applied to derive the interference field. The derived interference field along
with the phase-shifting concept is used for calculating the interfering
wavefronts. Our results show the success of this method even under noisy
conditions.
PMID- 27607980
TI - Near-field diffraction of chirped gratings.
AB - In this Letter, we analyze the near-field diffraction pattern produced by chirped
gratings. An intuitive analytical interpretation of the generated diffraction
orders is proposed. Several interesting properties of the near-field diffraction
pattern can be determined, such as the period of the fringes and its visibility.
Diffraction orders present different widths and also, some of them present
focusing properties. The width, location, and depth of focus of the converging
diffraction orders are also determined. The analytical expressions are compared
to numerical simulation and experimental results, showing a high agreement.
PMID- 27607981
TI - Mid-infrared multimode fiber-coupled quantum cascade laser for off-beam quartz
enhanced photoacoustic detection.
AB - A mid-infrared quartz-enhanced photoacoustic sensor was developed using a
multimode fiber (MMF)-coupled quantum cascade laser (QCL) and demonstrated for
sensitive nitric oxide (NO) detection at a wavelength near 5.26 MUm. The QCL
radiation was readily coupled into a solid-core InF3 MMF (100 MUm
core) with 97% coupling efficiency using an aspheric lens. Despite the 25.5%
transmission loss for the 1 m long MMF, the Gaussian beam-like fiber output of
5.72 degrees divergence was almost completely focused through the microresonator
tube (length, 8.0 mm; ID, 600 MUm) designed for off-beam quartz-enhanced
photoacoustic spectroscopy. The sensor exploiting the R6.5 (Pi21/2)
doublet of NO at 1900.08 cm-1 demonstrated a minimum detection limit
of 24 parts per billion by volume at an averaging time of 130 s. The sensor was
found to be insensitive to the fiber bending noise for a bending radius >5 cm.
PMID- 27607982
TI - Phase-change material-based nanoantennas with tunable radiation patterns.
AB - We suggest a novel switchable plasmonic dipole nanoantenna operating at mid
infrared frequencies that exploits phase-change materials. We show that the
induced dipole moments of a nanoantenna, where a germanium antimony telluride
(Ge3Sb2Te6 or GST for short) nanopatch acts as a
spacer between two coupled metallic nanopatches, can be controlled in a
disruptive sense. By switching GST between its crystalline and amorphous phases,
the nanoantenna can exhibit either an electric or a balanced magneto-electric
dipole-like radiation. While the former radiation pattern is omnidirectional, the
latter is directive. Based on this property exciting switching devices can be
perceived, such as a metasurface whose functionality can be switched between an
absorber and a reflector. The switching between stable amorphous and crystalline
phases occurs on timescales of nanoseconds and can be achieved by an electrical
or optical pulse.
PMID- 27607983
TI - Method for remotely measuring the spin-damping time of mesospheric sodium.
AB - By using the return flux enhancement factor due to repumping, the spin-damping
time of mesospheric sodium can be estimated. Because the absolute return photon
number does not need to be measured, this method is independent of sodium
abundance. An example of how to find the spin-damping time using this method is
given. As a result, it is shown that this method is sensitive and has the
potential to improve the precision of the spin-damping time estimations of
mesospheric sodium. Finally, the impact of the geomagnetic field on this method
is analyzed.
PMID- 27607984
TI - Localized waves supported by the rotating waveguide array.
AB - We show that truncated rotating square waveguide arrays support new types of
localized modes that exist even in the linear case, in complete contrast to
localized excitations in nonrotating arrays requiring nonlinearity for their
existence and forming above the energy flow threshold. These new modes appear
either around an array center, since the rotation leads to the emergence of the
effective attractive potential with a minimum at the rotation axis, or in the
array corners, in which case localization occurs due to competition between the
centrifugal force and total internal reflection at the interface of the truncated
array. The degree of localization of the central and corner modes mediated by the
rotation increases with the rotation frequency. The stable rotating soliton
families bifurcating from linear modes are analyzed in both focusing and
defocusing media.
PMID- 27607985
TI - Cylindrical Talbot effect for ultra-compact multimode interference couplers.
AB - Tapered multimode interference (MMI) couplers have been broadly studied for
applications in integrated photonic circuits due to their footprints being
smaller than conventional MMIs. The operation of an MMI is fundamentally related
to the Talbot effect. In this Letter, the Talbot effect is analyzed in
cylindrical coordinates, rather than conventional Cartesian coordinates. A
cylindrical geometry is found to result in a significant reduction of Talbot
distance and, hence, more compact MMIs. Simulation results are compared to
theoretical predictions to confirm the accuracy of the method.
PMID- 27607986
TI - Structured illumination assisted microdeflectometry with optical depth scanning
capability.
AB - Microdeflectometry is a powerful noncontact tool for measuring nanometer defects
on a freeform surface. However, it requires a time-consuming process to take
measurements at different depths for an extended depth of field (EDOF) and lacks
surface information for integrating the measured gradient data to height. We
propose an optical depth scanning technique to speed up the measurement process
and introduce the structured illumination technique to efficiently determine the
focused data among 3D observation and provide surface orientations for
reconstructing an unknown surface shape. We demonstrated 3D measurements with an
equivalent surface height sensitivity of 7.21 nm and an EDOF of at least 250 MUm,
which is 15 times that of the diffraction limited depth range.
PMID- 27607987
TI - Off-axis quartz-enhanced photoacoustic spectroscopy using a pulsed nanosecond mid
infrared optical parametric oscillator.
AB - A trace-gas sensor, based on quartz-enhanced photoacoustic spectroscopy (QEPAS),
consisting of two acoustically coupled micro-resonators (mR) with an off-axis 20
kHz quartz tuning fork (QTF) is demonstrated. The complete acoustically coupled
mR system is optimized based on finite-element simulations and is experimentally
verified. The QEPAS sensor is pumped resonantly by a nanosecond pulsed single
mode mid-infrared optical parametric oscillator. The sensor is used for
spectroscopic measurements on methane in the 3.1-3.5 MUm wavelength region with a
resolution bandwidth of 1 cm-1 and a detection limit of 0.8 ppm. An
Allan deviation analysis shows that the detection limit at the optimum
integration time for the QEPAS sensor is 32 ppbv at 190 s, and that the
background noise is due solely to the thermal noise of the QTF.
PMID- 27607988
TI - 56 Gb/s multi-band CAP for data center interconnects up to an 80 km SMF.
AB - We present the first (to the best of our knowledge) experimental demonstration of
a 56 Gb/s multi-band carrierless amplitude and phase modulation (CAP) signal
transmission over an 80-km single-mode fiber link with zero overhead pre-FEC
signal recovery and enhanced timing jitter tolerance for optical data center
interconnects.
PMID- 27607989
TI - Inverse polarizing effect of an elliptical-polarization recorded hologram at a
large cross angle.
AB - We report on the inverse polarizing effect (IPE) of an elliptical-polarization
recorded hologram at a large recording angle. The IPE is a polarizing phenomenon
in which the reconstructed signal switches the major and minor axes and keeps the
original polarization, direction compared, to that of the signal wave. In
reviewing the case of a linear-polarization and circular-polarization recorded
hologram, we found that the IPE is a unique phenomenon for elliptical
polarization. The IPE was observed at the cross angle of 38 degrees
experimentally, and was theoretically explained using tensor theory to remove
paraxial limitation.
PMID- 27607990
TI - Thulium-doped fiber chirped-pulse amplification system with 2 GW of peak power.
AB - Thulium-doped fibers with ultra large mode-field areas offer new opportunities
for the power scaling of mid-IR ultrashort-pulse laser sources. Here, we present
a laser system delivering a pulse-peak power of 2 GW and a nearly transform
limited pulse duration of 200 fs in combination with 28.7 W of average power.
This performance level has been achieved by optimizing the pulse shape, reducing
the overlap with atmospheric absorption lines, and incorporating a climate
chamber to reduce the humidity of the atmospheric environment.
PMID- 27607991
TI - Precise phase determination with the built-in spectral interferometry in two
dimensional electronic spectroscopy.
AB - A new method determining the precise phase of pulse sequences in two-dimensional
electronic spectroscopy (2DES) is proposed merely using the already built-in
spectral interferometry. The approach is easily implemented without the
supplementary instrumental construction, only at the expense of a few additional
scanning and data-fitting processes. This method is executed with the sample in
place, effectively avoiding the phase ambiguities of the beam propagation in
samples, thus calibrating the absolute phase at the exact interaction region. The
new proposed method is expected to improve the phasing procedure in 2DES in a
more convenient way.
PMID- 27607992
TI - Optical manipulation using optimal annular vortices.
AB - We discuss a simple method to generate a configurable annular vortex beam (AVB)
with the maximum possible peak intensity, employing a phase hologram whose
transmittance is the phase of a Bessel beam. Due to its maximum intensity, the
AVB provides the optimal density of the orbital angular moment. Another attribute
of the generated AVB is the relatively high invariance of the intensity profile
when the topological charge is changed. We demonstrate the advantages and
flexibility of these AVBs for optical trapping applications.
PMID- 27607993
TI - Optical gradient force assist maneuver.
AB - We describe an energy transfer process whereby a moving particle loses (or gains)
kinetic energy upon interacting with the moving optical potential of a swept beam
of light. This approach is akin to a gravitational assist maneuver for
interplanetary satellite propulsion. Special consideration is given to the
stopping condition. For analytical convenience, we examine the Rayleigh
scattering regime, providing examples at small and large scattering angles. A 5%
uncertainty in the initial particle speed and position has negligible effect on
the slowing/speeding ability when the beam size is much larger than the particle.
PMID- 27607994
TI - Surface and waveguide collection of Raman emission in waveguide-enhanced Raman
spectroscopy.
AB - We demonstrate Raman spectroscopy on a high index thin film tantalum pentoxide
waveguide and compare collection of Raman emission from the waveguide end with
that from the waveguide surface. Toluene was used as a convenient model analyte,
and a 40-fold greater signal was collected from the waveguide end. Simulations of
angular and spatial Raman emission distributions showed good agreement with
experiments, with the enhancement resulting from efficient collection of power
from dipoles near the surface into the high-index waveguide film and substrate,
combined with long interaction length. The waveguide employed was optimized at
the excitation wavelength but not at emission wavelengths, and full optimization
is expected to lead to enhancements comparable to surface-enhanced Raman
spectroscopy in robust low-cost metal-free and nanostructure-free chips.
PMID- 27607995
TI - Therapeutic and Preventive Implications of Moonshot in Hereditary Cancer
Syndromes.
PMID- 27607996
TI - Synthesis of beta-Difluoroalkylated Acrylonitriles in the Presence of Copper
Powder.
AB - A highly regio- and stereoselective copper-mediated cyanodifluoroalkylation of
alkynes with ethyl difluoroiodoacetate and trimethylsilyl cyanide (TMSCN) is
described. The three-component coupling reaction provides straightforward access
to a variety of useful difluoroalkyl-substituted acrylonitriles. The introduction
of the nitrile unit is of great importance in drug discovery for the modification
of this fragment. Preliminary mechanistic investigations indicate that a vinyl
iodide intermediate and a difluoroalkyl radical might be involved in this
transformation.
PMID- 27607997
TI - Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction
of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the
Terminal Oxidant.
AB - An efficient Pd(II)/Pd0-p-benzoquinone/hydroquinone-CuCl2/CuCl catalyst system
was developed that uses environmentally friendly molecular oxygen as the terminal
oxidant to catalyze the cyclization-carbonylation-cyclization coupling reaction
(CCC-coupling reaction) of (o-alkynyl phenyl) (methoxymethyl) sulfides.
PMID- 27607998
TI - Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne
Cycloaddition Reaction (CuAAC).
AB - The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar
cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated
an impressive number of reports, in the last years, focusing on recoverable
variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in
the field are reviewed, with particular emphasis on systems immobilized onto
polymeric organic or inorganic supports.
PMID- 27607999
TI - Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional
Magnetic Submicron Particles in Prostate Cancer Cells.
AB - In this study, newly designed biocompatible multifunctional magnetic submicron
particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were
fabricated for application as a photosensitizer delivery agent for photodynamic
therapy in cancer cells. To provide selective targeting of cancer cells and
destruction of cancer cell functionality, basic cobalt ferrite (CoFe2O4)
particles were covalently bonded with a photosensitizer (PS), which comprises
hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of
the CoFe2O4 particles were finely adjusted by controlling the size of the primary
CoFe2O4 nanograins, and secondary superstructured composite particles were formed
by aggregation of the nanograins. The prepared CoFe2O4-HP-FA exhibited high water
solubility, good MR-imaging capacity, and biocompatibility without any in vitro
cytotoxicity. In particular, our CoFe2O4-HP-FA exhibited remarkable photodynamic
anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer
cells in a particle size- and concentration-dependent manner. This size-dependent
effect was determined by the specific surface area of the particles because the
number of HP molecules increased with decreasing size and increasing surface
area. These results indicate that our CoFe2O4-HP-FA may be applicable for
photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for
MR-imaging based PDT owing to their high saturation value for magnetization and
superparamagnetism.
PMID- 27608000
TI - Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported
Chiral Picolinamides.
AB - The stereoselective reduction of imines with trichlorosilane catalyzed by chiral
Lewis bases is a well-established procedure for the synthesis of enantio-enriched
amines. Five supported cinchona-based picolinamides have been prepared and their
activity tested in a model reaction. The comparison of different supporting
materials revealed that polystyrene gave better results than silica in terms of
stereoselectivity. The applicability of the solid-supported catalyst of choice to
the reduction of different imines was also demonstrated. Additionally, for the
first time, a catalytic reactor containing a polymer-immobilized chiral
picolinamide has been employed for the stereoselective reduction of imines with
trichlorosilane under continuous flow conditions.
PMID- 27608001
TI - Structural Features of Alkaline Extracted Polysaccharide from the Seeds of
Plantago asiatica L. and Its Rheological Properties.
AB - Polysaccharide from the seeds of Plantago asiatica L. has many bioactivities, but
few papers report on the structural and rheological characteristics of the
alkaline extract. The alkaline extracted polysaccharide was prepared from seeds
of P. asiatica L. and named herein as alkaline extracted polysaccharide from
seeds of P. asiatica L. (PLAP). Its structural and rheological properties were
characterized by monosaccharide composition, methylation, GC-MS and rheometry.
PLAP, as an acidic arabinoxylan, was mainly composed of 1,2,4-linked Xylp and
1,3,4-linked Xylp residues. PLAP solution showed pseudoplastic behavior, and weak
gelling properties at high concentration. Sodium and especially calcium ions
played a significant role in increasing the apparent viscosity and gel strength.
PMID- 27608002
TI - A Review on the Terpenes from Genus Vitex.
AB - The genus Vitex, which belongs to the Verbenaceae family, includes approximately
250 species. Some species of the genus Vitex have traditionally been used for the
treatment of headaches, ophthalmodynia, coughs, asthma, premenopausal syndrome,
etc. Chemical investigations indicate that the characteristic constituents of the
genus Vitex are terpenes, and 210 of these compounds, including monoterpenoids,
sesquiterpenoids, diterpenoids and triterpenoids, have been obtained from 12
species. Pharmacological studies had shown that these terpenes possess anti
inflammatory, antitumor, antibacterial, antioxidant activities, and so on. In
this paper, the identity of these terpenes and their pharmacological effects are
reviewed, which can provide references for further research regarding the
chemistry and utilization of the Vitex species.
PMID- 27608003
TI - Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril:
An Experimental and Computational Study.
AB - The histamine H2-receptor antagonists cimetidine, famotidine and nizatidine are
individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding
affinities of 6.57 (+/-0.19) * 103 M(-1), 1.30 (+/-0.27) * 104 M(-1) and 1.05 (+/
0.33) * 105 M(-1), respectively. These 1:1 host-guest inclusion complexes have
been experimentally examined by 1H-NMR, UV-visible spectroscopic titrations
(including Job plots), electrospray ionization mass spectrometry (ESI-MS), and
isothermal titration calorimetry (ITC), as well as theoretically by molecular
dynamics (MD) computation. This study may provide important insights on the
supramolecular formulation of H2-receptor antagonist drugs for potentially
enhanced stability and controlled release based on different binding strengths of
these host-guest complexes.
PMID- 27608004
TI - Synthesis Approaches to (-)-Cytoxazone, a Novel Cytokine Modulator, and Related
Structures.
AB - (-)-Cytoxazone, originally isolated from cultures of a Streptomyces species has
an oxazolidin-2-one 4,5-disubstituted ring. It is known that this natural product
presents a cytokine modulator effect through the signaling pathway of Th2 cells
(type 2 cytokines), which are involved in the process of growth and
differentiation of cells. From this, the interest in the development of research
aimed at the total synthesis of this molecule and its analogs has remained high,
which can be confirmed by the large number of publications on the topic, more
than 30 to date. This review focuses on the various creative methods for the
synthesis of (-)-cytoxazone and its congeners. The assessment of the preparation
of this oxazolidinone and related structures serves as a treatise on the efforts
made in the synthesis of this important class of compound from its first total
synthesis in 1999.
PMID- 27608005
TI - MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on
Ischemia/Reperfusion Injury in Rats.
AB - As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic
astrocyte-derived neurotrophic factor (MANF) has been proven to protect
dopaminergic neurons and nondopaminergic cells. Our previous studies had shown
that MANF protected against ischemia/reperfusion injury. Here, we developed a
magnetic resonance imaging (MRI) technology to dynamically evaluate the
therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat
focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was
performed to investigate the dynamics of lesion formation. MANF protein was
injected into the right lateral ventricle at 3 h after reperfusion following MCAO
for 90 min, when the obvious lesion firstly appeared according to MRI
investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF
protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and
7 post-reperfusion combined with histology methods. The results indicated that
the administration of MANF protein at the early stage after ischemia/reperfusion
injury decreased the mortality, improved the neurological function, reduced the
cerebral infarct volume, and alleviated the brain tissue injury. The findings
collected from MRI are consistent with the morphological and pathological
changes, which suggest that MRI is a useful technology for evaluating the
therapeutic effects of drugs.
PMID- 27608006
TI - Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7
in Diabetes and Painful Diabetic Neuropathy.
AB - Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its
complications is painful peripheral neuropathy, which can substantially erode
quality of life and increase the cost of management. Despite its clinical
importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and
incompletely understood. Voltage-gated sodium channels (VGSCs) link many
physiological processes to electrical activity by controlling action potentials
in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which
are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and
Scn9A) genes, respectively, have been identified in both peripheral nociceptive
neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances
in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and
NaV1.7 lead to the rational doubt about the cause-effect relation between
diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3
and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and
painful neuropathy, and present a model, which may provide a starting point for
further studies aimed at identifying the mechanisms underlying diabetes and
painful neuropathy.
PMID- 27608007
TI - Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant
Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients.
AB - BACKGROUND: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy
(CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of
patients. A pathway based-approach could highlight the predictive role of
germline single nucleotide polymorphisms (SNPs). The primary aim of this study
was to define new predictive biomarkers considering treatment specificities.
Secondary aim was to determine new potential predictive biomarkers independent
from radiotherapy (RT) dosage and cotreatment with oxaliplatin. METHODS: Thirty
germ-line SNPs in twenty-one genes were selected according to a pathway-based
approach. Genetic analyses were performed on 280 LARC patients who underwent
fluoropyrimidine-based CRT. The potential predictive role of these SNPs in
determining pathological tumor response was tested in Group 1 (94 patients
undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage),
Group 3 (113 patients treated with standard RT dosage), and in the pooled
population (280 patients). RESULTS: Nine new predictive biomarkers were
identified in the three groups. The most promising one was rs3136228-MSH6 (p =
0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed
only a trend (p = 0.073). CONCLUSION: This exploratory study highlighted new
potential predictive biomarkers of neoadjuvant CRT and underlined the importance
to strictly define treatment peculiarities in pharmacogenetic analyses.
PMID- 27608008
TI - Antimicrobial and Antioxidant Activity of Chitosan/Hydroxypropyl Methylcellulose
Film-Forming Hydrosols Hydrolyzed by Cellulase.
AB - The aim of this study was to evaluate the impact of cellulase (C) on the
biological activity of chitosan/hydroxypropyl methylcellulose (CH/HPMC) film
forming hydrosols. The hydrolytic activity of cellulase in two concentrations
(0.05% and 0.1%) was verified by determination of the progress of polysaccharide
hydrolysis, based on viscosity measurement and reducing sugar-ends assay. The 2,2
diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging effect, the ferric
reducing antioxidant power (FRAP), and microbial reduction of Pseudomonas
fluorescens, Yersinia enterocolitica, Bacillus cereus, and Staphylococcus aureus
were studied. During the first 3 h of reaction, relative reducing sugar
concentration increased progressively, and viscosity decreased rapidly. With
increasing amount of enzyme from 0.05% to 0.1%, the reducing sugar concentration
increased, and the viscosity decreased significantly. The scavenging effect of
film-forming solutions was improved from 7.6% at time 0 and without enzyme to
52.1% for 0.1% cellulase after 20 h of reaction. A significant effect of
cellulase addition and reaction time on antioxidant power of the tested film
forming solutions was also reported. Film-forming hydrosols with cellulase
exhibited a bacteriostatic effect on all tested bacteria, causing a total
reduction.
PMID- 27608010
TI - Regulation of Translocator Protein 18 kDa (TSPO) Expression in Rat and Human Male
Germ Cells.
AB - Translocator protein 18 kDa (TSPO) is a high affinity cholesterol- and drug
binding protein highly expressed in steroidogenic cells, such as Leydig cells,
where it plays a role in cholesterol mitochondrial transport. We have previously
shown that TSPO is expressed in postnatal day 3 rat gonocytes, precursors of
spermatogonial stem cells. Gonocytes undergo regulated phases of proliferation
and migration, followed by retinoic acid (RA)-induced differentiation.
Understanding these processes is important since their disruption may lead to the
formation of carcinoma in situ, a precursor of testicular germ cell tumors
(TGCTs). Previously, we showed that TSPO ligands do not regulate gonocyte
proliferation. In the present study, we found that TSPO expression is
downregulated in differentiating gonocytes. Similarly, in F9 embryonal carcinoma
cells, a mouse TGCT cell line with embryonic stem cell properties, there is a
significant decrease in TSPO expression during RA-induced differentiation.
Silencing TSPO expression in gonocytes increased the stimulatory effect of RA on
the expression of the differentiation marker Stra8, suggesting that TSPO exerts a
repressive role on differentiation. Furthermore, in normal human testes, TSPO was
located not only in Leydig cells, but also in discrete spermatogenic phases such
as the forming acrosome of round spermatids. By contrast, seminomas, the most
common type of TGCT, presented high levels of TSPO mRNA. TSPO protein was
expressed in the cytoplasmic compartment of seminoma cells, identified by their
nuclear expression of the transcription factors OCT4 and AP2G. Thus, TSPO appears
to be tightly regulated during germ cell differentiation, and to be deregulated
in seminomas, suggesting a role in germ cell development and pathology.
PMID- 27608011
TI - Affinity of (nat/68)Ga-Labelled Curcumin and Curcuminoid Complexes for beta
Amyloid Plaques: Towards the Development of New Metal-Curcumin Based
Radiotracers.
AB - Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently
shown their potential as diagnostic tools for Alzheimer's disease. Nevertheless,
no study by exploiting the labelling with gallium-68 has been performed so far,
in spite of its suitable properties (positron emitter, generator produced
radionuclide). Herein, an evaluation of the affinity for synthetic beta-amyloid
fibrils and for amyloid plaques of three (nat/68)Ga-labelled curcumin analogues,
namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl
curcumin (DAC), was performed. Affinity and specificity were tested in vitro on
amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem
brain cryosections from Tg2576 mice were used for the ex vivo visualization of
amyloid plaques. The affinity of (68)Ga(CUR)2+, (68)Ga(DAC)2+, and (68)Ga(bDHC)2+
for synthetic beta-amyloid fibrils was moderate and their uptake could be
observed in vitro. On the other hand, amyloid plaques could not be visualized on
brain sections of Tg2576 mice after injection, probably due to the low stability
of the complexes in vivo and of a hampered passage through the blood-brain
barrier. Like curcumin, all (nat/68)Ga-curcuminoid complexes maintain a high
affinity for beta-amyloid plaques. However, structural modifications are still
needed to improve their applicability as radiotracers in vivo.
PMID- 27608009
TI - Current Status of Long Non-Coding RNAs in Human Breast Cancer.
AB - Breast cancer represents a major health burden in Europe and North America, as
recently published data report breast cancer as the second leading cause of
cancer related death in women worldwide. Breast cancer is regarded as a highly
heterogeneous disease in terms of clinical course and biological behavior and can
be divided into several molecular subtypes, with different prognosis and
treatment responses. The discovery of numerous non-coding RNAs has dramatically
changed our understanding of cell biology, especially the pathophysiology of
cancer. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts >200
nucleotides in length. Several studies have demonstrated their role as key
regulators of gene expression, cell biology and carcinogenesis. Deregulated
expression levels of lncRNAs have been observed in various types of cancers
including breast cancer. lncRNAs are involved in cancer initiation, progression,
and metastases. In this review, we summarize the recent literature to highlight
the current status of this class of long non-coding lncRNAs in breast cancer.
PMID- 27608014
TI - Drug, Herb, and Dietary Supplement Hepatotoxicity.
AB - The past decade has witnessed drugs, herbs, and dietary supplements share the
common feature of potential liver injury in a few susceptible individuals.[...].
PMID- 27608012
TI - Mammalian Metallothionein-2A and Oxidative Stress.
AB - Mammalian metallothionein-2A (MT2A) has received considerable attention in recent
years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis,
detoxification and anti-inflammation. For many years, most studies evaluating the
effects of MT2A have focused on reactive oxygen species (ROS), as second
messengers that lead to oxidative stress injury of cells and tissues. Recent
studies have highlighted that oxidative stress could activate mitogen-activated
protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the
pathogenesis of various diseases. However, the molecule mechanism of MT2A remains
elusive. A deeper understanding of the functional, biochemical and molecular
characteristics of MT2A would be identified, in order to bring new opportunities
for oxidative stress therapy.
PMID- 27608013
TI - Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS
Study and a Meta-Analysis of Prospective Studies.
AB - To investigate the association between serum calcium and risk of breast cancer
using a large cohort and a systematic review with meta-analysis. From the Swedish
Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had
baseline measurements of serum total calcium and albumin. Multivariable Cox
regression was used to assess the association between total and albumin-corrected
calcium and breast cancer risk. For the systematic review, an electronic search
of MEDLINE and EMBASE databases was performed to identify other prospective
cohorts assessing the relationship between serum calcium and breast cancer risk.
We pooled the results of our AMORIS cohort with other eligible studies in a meta
analysis using a random effects model. I2 test was used to assess heterogeneity.
In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow
up: 19 years). We found an inverse association between total serum calcium and
breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94,
95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin
corrected calcium. In the systematic review, we identified another two
prospective cohorts evaluating pre-diagnostic serum total calcium and breast
cancer. Combining these studies and our findings in AMORIS in a meta-analysis
showed a protective effect of serum calcium against breast cancer, with a summary
RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our
findings in AMORIS and the meta-analysis support an inverse association between
serum calcium and breast cancer risk, which warrants mechanistic investigations.
PMID- 27608015
TI - Diabetes and Hypertension Consistently Predict the Presence and Extent of
Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and
Meta-Analysis.
AB - BACKGROUND: The relationship of conventional cardiovascular risk factors (age,
gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and
the number of risk factors) to coronary artery calcification (CAC) presence and
extent has never before been assessed in a systematic review and meta-analysis.
METHODS: We included only English language studies that assessed at least three
conventional risk factors apart from age, gender, and ethnicity, but excluded
studies in which all patients had another confirmed condition such as renal
disease. RESULTS: In total, 10 studies, comprising 15,769 patients, were
investigated in the systematic review and seven studies, comprising 12,682
patients, were included in the meta-analysis, which demonstrated the importance
of diabetes and hypertension as predictors of CAC presence and extent, with age
also predicting CAC presence. Male gender, dyslipidaemia, family history of
coronary artery disease, obesity, and smoking were overall not predictive of
either CAC presence or extent, despite dyslipidaemia being a key risk factor for
coronary artery disease (CAD). CONCLUSION: Diabetes and hypertension consistently
predict the presence and extent of CAC in symptomatic patients.
PMID- 27608018
TI - Neural Network-Based Self-Tuning PID Control for Underwater Vehicles.
AB - For decades, PID (Proportional + Integral + Derivative)-like controllers have
been successfully used in academia and industry for many kinds of plants. This is
thanks to its simplicity and suitable performance in linear or linearized plants,
and under certain conditions, in nonlinear ones. A number of PID controller gains
tuning approaches have been proposed in the literature in the last decades; most
of them off-line techniques. However, in those cases wherein plants are subject
to continuous parametric changes or external disturbances, online gains tuning is
a desirable choice. This is the case of modular underwater ROVs (Remotely
Operated Vehicles) where parameters (weight, buoyancy, added mass, among others)
change according to the tool it is fitted with. In practice, some amount of time
is dedicated to tune the PID gains of a ROV. Once the best set of gains has been
achieved the ROV is ready to work. However, when the vehicle changes its tool or
it is subject to ocean currents, its performance deteriorates since the fixed set
of gains is no longer valid for the new conditions. Thus, an online PID gains
tuning algorithm should be implemented to overcome this problem. In this paper,
an auto-tune PID-like controller based on Neural Networks (NN) is proposed. The
NN plays the role of automatically estimating the suitable set of PID gains that
achieves stability of the system. The NN adjusts online the controller gains that
attain the smaller position tracking error. Simulation results are given
considering an underactuated 6 DOF (degrees of freedom) underwater ROV. Real time
experiments on an underactuated mini ROV are conducted to show the effectiveness
of the proposed scheme.
PMID- 27608017
TI - The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review
of Clinical Evidence.
AB - The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan)
represents a new iteration in drug-eluting stent (DES) technology that has
recently received the Conformite Europeenne (CE) mark approval for clinical use.
The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus
eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA
PCL) and the abluminal gradient coating technology are additional novel features
of this coronary device. The Ultimaster DES has undergone extensive clinical
evaluation in two studies: The CENTURY I and II trials. Results from these two
landmark studies suggested an excellent efficacy and safety profile of the
Ultimaster DES across several lesion and patient subsets, with similar clinical
outcomes to contemporary, new-generation DES. The aim of this review is to
summarize the rationale behind this novel DES technology and to provide an update
of available evidence about the clinical performance of the Ultimaster DES.
PMID- 27608019
TI - Continuous Indoor Positioning Fusing WiFi, Smartphone Sensors and Landmarks.
AB - To exploit the complementary strengths of WiFi positioning, pedestrian dead
reckoning (PDR), and landmarks, we propose a novel fusion approach based on an
extended Kalman filter (EKF). For WiFi positioning, unlike previous fusion
approaches setting measurement noise parameters empirically, we deploy a kernel
density estimation-based model to adaptively measure the related measurement
noise statistics. Furthermore, a trusted area of WiFi positioning defined by
fusion results of previous step and WiFi signal outlier detection are exploited
to reduce computational cost and improve WiFi positioning accuracy. For PDR, we
integrate a gyroscope, an accelerometer, and a magnetometer to determine the user
heading based on another EKF model. To reduce accumulation error of PDR and
enable continuous indoor positioning, not only the positioning results but also
the heading estimations are recalibrated by indoor landmarks. Experimental
results in a realistic indoor environment show that the proposed fusion approach
achieves substantial positioning accuracy improvement than individual positioning
approaches including PDR and WiFi positioning.
PMID- 27608016
TI - Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.
AB - Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer".
Consequently, during the last decades the development and testing of commercial
angiogenic inhibitors has been a central focus for both basic and clinical cancer
research. While antiangiogenic drugs are now incorporated into standard clinical
practice, as with all cancer therapies, tumors can eventually become resistant by
employing a variety of strategies to receive nutrients and oxygen in the event of
therapeutic assault. Herein, we concentrate and review in detail three of the
principal mechanisms of antiangiogenic therapy escape: (1) upregulation of
compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and
(3) vessel co-option. We suggest that an understanding of how a cancer cell
adapts to antiangiogenic therapy may also parallel the mechanisms employed in the
bourgeoning tumor and isolated metastatic cells delivering responsible for
residual disease. Finally, we speculate on strategies to adapt antiangiogenic
therapy for future clinical uses.
PMID- 27608020
TI - Effect of Sensors on the Reliability and Control Performance of Power Circuits in
the Web of Things (WoT).
AB - In order to realize a true WoT environment, a reliable power circuit is required
to ensure interconnections among a range of WoT devices. This paper presents
research on sensors and their effects on the reliability and response
characteristics of power circuits in WoT devices. The presented research can be
used in various power circuit applications, such as energy harvesting interfaces,
photovoltaic systems, and battery management systems for the WoT devices. As
power circuits rely on the feedback from voltage/current sensors, the system
performance is likely to be affected by the sensor failure rates, sensor dynamic
characteristics, and their interface circuits. This study investigated how the
operational availability of the power circuits is affected by the sensor failure
rates by performing a quantitative reliability analysis. In the analysis process,
this paper also includes the effects of various reconstruction and estimation
techniques used in power processing circuits (e.g., energy harvesting circuits
and photovoltaic systems). This paper also reports how the transient control
performance of power circuits is affected by sensor interface circuits. With the
frequency domain stability analysis and circuit simulation, it was verified that
the interface circuit dynamics may affect the transient response characteristics
of power circuits. The verification results in this paper showed that the
reliability and control performance of the power circuits can be affected by the
sensor types, fault tolerant approaches against sensor failures, and the response
characteristics of the sensor interfaces. The analysis results were also verified
by experiments using a power circuit prototype.
PMID- 27608021
TI - Modeling of Distributed Sensing of Elastic Waves by Fiber-Optic Interferometry.
AB - This paper deals with the transduction of strain accompanying elastic waves in
solids by firmly attached optical fibers. Stretching sections of optical fibers
changes the time required by guided light to pass such sections. Exploiting
interferometric techniques, highly sensitive fiber-optic strain transducers are
feasible based on this fiber-intrinsic effect. The impact on the actual strain
conversion of the fiber segment's shape and size, as well as its inclination to
the elastic wavefront is studied. FEM analyses show that severe distortions of
the interferometric response occur when the attached fiber length spans a
noticeable fraction of the elastic wavelength. Analytical models of strain
transduction are presented for typical transducer shapes. They are used to
compute input-output relationships for the transduction of narrow-band strain
pulses as a function of the mechanical wavelength. The described approach applies
to many transducers depending on the distributed interaction with the
investigated object.
PMID- 27608022
TI - A Greedy Scanning Data Collection Strategy for Large-Scale Wireless Sensor
Networks with a Mobile Sink.
AB - Mobile sink is widely used for data collection in wireless sensor networks. It
can avoid 'hot spot' problems but energy consumption caused by multihop
transmission is still inefficient in real-time application scenarios. In this
paper, a greedy scanning data collection strategy (GSDCS) is proposed, and we
focus on how to reduce routing energy consumption by shortening total length of
routing paths. We propose that the mobile sink adjusts its trajectory dynamically
according to the changes of network, instead of predetermined trajectory or
random walk. Next, the mobile sink determines which area has more source nodes,
then it moves toward this area. The benefit of GSDCS is that most source nodes
are no longer needed to upload sensory data for long distances. Especially in
event-driven application scenarios, when event area changes, the mobile sink
could arrive at the new event area where most source nodes are located currently.
Hence energy can be saved. Analytical and simulation results show that compared
with existing work, our GSDCS has a better performance in specific application
scenarios.
PMID- 27608024
TI - Noise Suppression on the Tunable Laser for Precise Cavity Length Displacement
Measurement.
AB - The absolute distance between the mirrors of a Fabry-Perot cavity with a spacer
from an ultra low expansion material was measured by an ultra wide tunable laser
diode. The DFB laser diode working at 1542 nm with 1.5 MHz linewidth and 2 nm
tuning range has been suppressed with an unbalanced heterodyne fiber
interferometer. The frequency noise of laser has been suppressed by 40 dB across
the Fourier frequency range 30-300 Hz and by 20 dB up to 4 kHz and the linewidth
of the laser below 300 kHz. The relative resolution of the measurement was 10 - 9
that corresponds to 0.3 nm (sub-nm) for 0.178 m long cavity with ability of
displacement measurement of 0.5 mm.
PMID- 27608025
TI - Testing the Suitability of a Terrestrial 2D LiDAR Scanner for Canopy
Characterization of Greenhouse Tomato Crops.
AB - Canopy characterization is essential for pesticide dosage adjustment according to
vegetation volume and density. It is especially important for fresh exportable
vegetables like greenhouse tomatoes. These plants are thin and tall and are
planted in pairs, which makes their characterization with electronic methods
difficult. Therefore, the accuracy of the terrestrial 2D LiDAR sensor is
evaluated for determining canopy parameters related to volume and density and
established useful correlations between manual and electronic parameters for leaf
area estimation. Experiments were performed in three commercial tomato
greenhouses with a paired plantation system. In the electronic characterization,
a LiDAR sensor scanned the plant pairs from both sides. The canopy height, canopy
width, canopy volume, and leaf area were obtained. From these, other important
parameters were calculated, like the tree row volume, leaf wall area, leaf area
index, and leaf area density. Manual measurements were found to overestimate the
parameters compared with the LiDAR sensor. The canopy volume estimated with the
scanner was found to be reliable for estimating the canopy height, volume, and
density. Moreover, the LiDAR scanner could assess the high variability in canopy
density along rows and hence is an important tool for generating canopy maps.
PMID- 27608023
TI - Web of Objects Based Ambient Assisted Living Framework for Emergency Psychiatric
State Prediction.
AB - Ambient assisted living can facilitate optimum health and wellness by aiding
physical, mental and social well-being. In this paper, patients' psychiatric
symptoms are collected through lightweight biosensors and web-based psychiatric
screening scales in a smart home environment and then analyzed through machine
learning algorithms to provide ambient intelligence in a psychiatric emergency.
The psychiatric states are modeled through a Hidden Markov Model (HMM), and the
model parameters are estimated using a Viterbi path counting and scalable
Stochastic Variational Inference (SVI)-based training algorithm. The most likely
psychiatric state sequence of the corresponding observation sequence is
determined, and an emergency psychiatric state is predicted through the proposed
algorithm. Moreover, to enable personalized psychiatric emergency care, a service
a web of objects-based framework is proposed for a smart-home environment. In
this framework, the biosensor observations and the psychiatric rating scales are
objectified and virtualized in the web space. Then, the web of objects of sensor
observations and psychiatric rating scores are used to assess the dweller's
mental health status and to predict an emergency psychiatric state. The proposed
psychiatric state prediction algorithm reported 83.03 percent prediction accuracy
in an empirical performance study.
PMID- 27608026
TI - Enhancement of Kinematic Accelerations by Wavenumber Correlation Filtering.
AB - To obtain kinematic accelerations with high accuracy and reliability, multiple
Global Positioning System (GPS) receivers with a single antenna can be used for
airborne gravimetry. The data collected from each receiver can be processed for
kinematic accelerations that may be combined using simple averaging. Here,
however, uncorrelated errors from instrument errors in each receiver also will be
included that degrade the final solutions. Therefore, in this study, the
wavenumber correlation filter (WCF) is applied to extract only the higher
positively correlated wavenumber components of the kinematic accelerations for
the enhancement of the final solution. The in situ airborne GPS data from two
receivers were wavenumber-correlation-filtered to show about 0.07835 Gal
improvement in accuracy relative to the solution from the raw kinematic
accelerations.
PMID- 27608027
TI - Effects of AlN Coating Layer on High Temperature Characteristics of Langasite SAW
Sensors.
AB - High temperature characteristics of langasite surface acoustic wave (SAW) devices
coated with an AlN thin film have been investigated in this work. The AlN films
were deposited on the prepared SAW devices by mid-frequency magnetron sputtering.
The SAW devices coated with AlN films were measured from room temperature to 600
degrees C. The results show that the SAW devices can work up to 600 degrees C.
The AlN coating layer can protect and improve the performance of the SAW devices
at high temperature. The SAW velocity increases with increasing AlN coating layer
thickness. The temperature coefficients of frequency (TCF) of the prepared SAW
devices decrease with increasing thickness of AlN coating layers, while the
electromechanical coupling coefficient (K2) of the SAW devices increases with
increasing AlN film thickness. The K2 of the SAW devices increases by about 20%
from room temperature to 600 degrees C. The results suggest that AlN coating
layer can not only protect the SAW devices from environmental contamination, but
also improve the K2 of the SAW devices.
PMID- 27608028
TI - Selectivity Enhancement by Using Double-Layer MOX-Based Gas Sensors Prepared by
Flame Spray Pyrolysis (FSP).
AB - Here we present a novel concept for the selective recognition of different target
gases with a multilayer semiconducting metal oxide (SMOX)-based sensor device.
Direct current (DC) electrical resistance measurements were performed during
exposure to CO and ethanol as single gases and mixtures of highly porous metal
oxide double- and single-layer sensors obtained by flame spray pyrolysis. The
results show that the calculated resistance ratios of the single- and double
layer sensors are a good indicator for the presence of specific gases in the
atmosphere, and can constitute some building blocks for the development of
chemical logic devices. Due to the inherent lack of selectivity of SMOX-based gas
sensors, such devices could be especially relevant for domestic applications.
PMID- 27608029
TI - The Non-Destructive Test of Steel Corrosion in Reinforced Concrete Bridges Using
a Micro-Magnetic Sensor.
AB - This paper presents a non-destructive test method for steel corrosion in
reinforced concrete bridges by using a 3-dimensional digital micro-magnetic
sensor to detect and analyze the self-magnetic field leakage from corroded
reinforced concrete. The setup of the magnetic scanning device and the
measurement mode of the micro-magnetic sensor are introduced. The numerical
analysis model is also built based on the linear magnetic charge theory. Compared
to the self-magnetic field leakage data obtained from magnetic sensor-based
measurement and numerical calculation, it is shown that the curves of tangential
magnetic field at different lift-off height all intersect near the edge of the
steel corrosion zone. The result indicates that the intersection of magnetic
field curves can be used to detect and evaluate the range of the inner steel
corrosion in engineering structures. The findings of this work propose a new and
effective non-destructive test method for steel corrosion, and therefore enlarge
the application of the micro-magnetic sensor.
PMID- 27608030
TI - The Role of Antimicrobial Peptides in Influenza Virus Infection and Their
Potential as Antiviral and Immunomodulatory Therapy.
AB - Influenza A virus (IAV) remains a major threat that can cause severe morbidity
and mortality due to rapid genomic variation. Resistance of IAVs to current anti
IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been
considered to be potential candidates for novel treatment against IAV infection.
AMPs are endogenous proteins playing important roles in host defense through
direct antimicrobial and antiviral activities and through immunomodulatory
effects. In this review, we will discuss the anti-IAV and immunomodulatory
effects of classical AMPs (defensins and cathelicidins), and proteins more
recently discovered to have AMP-like activity (histones and Alzheimer's
associated beta-amyloid). We will discuss the interactions between AMPs and other
host defense proteins. Major emphasis will be placed on novel synthetic AMPs
derived from modification of natural proteins, and on potential methods of
increasing expression of endogenous AMPs, since these approaches may lead to
novel antiviral therapeutics.
PMID- 27608032
TI - Biodegradation of Methyl tert-Butyl Ether by Co-Metabolism with a Pseudomonas sp.
Strain.
AB - Co-metabolic bioremediation is supposed to be an impressive and promising
approach in the elimination technology of methyl tert-butyl ether (MTBE), which
was found to be a common pollutant worldwide in the ground or underground water
in recent years. In this paper, bacterial strain DZ13 (which can co-metabolically
degrade MTBE) was isolated and named as Pseudomonas sp. DZ13 based on the result
of 16S rRNA gene sequencing analysis. Strain DZ13 could grow on n-alkanes (C5
C8), accompanied with the co-metabolic degradation of MTBE. Diverse n-alkanes
with different carbon number showed a significant influence on the degradation
rate of MTBE and accumulation of tert-butyl alcohol (TBA). When Pseudomonas sp.
DZ13 co-metabolically degraded MTBE with n-pentane as the growth substrate, a
higher MTBE-degrading rate (Vmax = 38.1 nmol/min/mgprotein, Ks = 6.8 mmol/L) and
lower TBA-accumulation was observed. In the continuous degradation experiment,
the removal efficiency of MTBE by Pseudomonas sp. Strain DZ13 did not show an
obvious decrease after five times of continuous addition.
PMID- 27608031
TI - Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the
Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta
Analysis.
AB - BACKGROUND: Previous studies have evaluated the associations between the
cholesteryl ester transfer protein (CETP) TaqIB polymorphism (rs708272), the risk
of developing composite ischemic cardiovascular disease (CVD) and the
concentration of high-density lipoprotein cholesterol (HDL-C), but results remain
controversial. The objective of this study was to investigate whether a
relationship exists between these factors. METHODS: We conducted a meta-analysis
of available studies to clarify the associations of the CETP TaqIB polymorphism
with HDL-C concentration and the composite ischemic CVD risk in both Asians and
Caucasians. All statistical analyses were done with Stata 12.0. RESULTS: Through
utilization of the Cochrane Library, Embase, PubMed, Web of Science, Springer,
China Science and Technology Journal Database, China National Knowledge
Infrastructure, Google Scholar, and Baidu Library, a total of 45 studies from 44
papers with 20,866 cases and 21,298 controls were combined showing a significant
association between the CETP TaqIB variant and composite ischemic CVD risk.
Carriers of allele TaqIB-B1 were found to have a higher risk of composite
ischemic CVD than non-carriers: OR = 1.15, 95% CI = 1.09-1.21, p < 0.001.
Meanwhile, 28 studies with 23,959 subjects were included in the association
between the CETP TaqIB polymorphism and the concentration of HDL-C. RESULTS
suggested that carriers of the B1B1 genotype had lower concentrations of HDL-C
than those of the B2B2 genotype: SMD = 0.50, 95% CI = 0.36-0.65, p < 0.001.
CONCLUSIONS: The synthesis of available evidence demonstrates that the CETP TaqIB
polymorphism protects against composite ischemic CVD risk and is associated with
a higher HDL-C concentration in both Asians and Caucasians.
PMID- 27608033
TI - In Situ, High-Resolution Profiles of Labile Metals in Sediments of Lake Taihu.
AB - Characterizing labile metal distribution and biogeochemical behavior in sediments
is crucial for understanding their contamination characteristics in lakes, for
which in situ, high-resolution data is scare. The diffusive gradient in thin
films (DGT) technique was used in-situ at five sites across Lake Taihu in the
Yangtze River delta in China to characterize the distribution and mobility of
eight labile metals (Fe, Mn, Zn, Ni, Cu, Pb, Co and Cd) in sediments at a 3 mm
spatial resolution. The results showed a great spatial heterogeneity in the
distributions of redox-sensitive labile Fe, Mn and Co in sediments, while other
metals had much less marked structure, except for downward decreases of labile
Pb, Ni, Zn and Cu in the surface sediment layers. Similar distributions were
found between labile Mn and Co and among labile Ni, Cu and Zn, reflecting a close
link between their geochemical behaviors. The relative mobility, defined as the
ratio of metals accumulated by DGT to the total contents in a volume of sediments
with a thickness of 10 mm close to the surface of DGT probe, was the greatest for
Mn and Cd, followed by Zn, Ni, Cu and Co, while Pb and Fe had the lowest
mobility; this order generally agreed with that defined by the modified BCR
approach. Further analyses showed that the downward increases of pH values in
surface sediment layer may decrease the lability of Pb, Ni, Zn and Cu as detected
by DGT, while the remobilization of redox-insensitive metals in deep sediment
layer may relate to Mn cycling through sulphide coprecipitation, reflected by
several corresponding minima between these metals and Mn. These in situ data
provided the possibility for a deep insight into the mechanisms involved in the
remobilization of metals in freshwater sediments.
PMID- 27608034
TI - Perceived Relative Harm of Selected Cigarettes and Non-Cigarette Tobacco Products
A Study of Young People from a Socio-Economically Disadvantaged Rural Area in
Poland.
AB - The perceived health risk of recently introduced nicotine and tobacco products
may influence both their uptake and continued use. The aim of the study was to
assess how adolescents rate relative harmfulness of slim and menthol cigarettes,
water pipes, e-cigarettes, and smokeless tobacco compared to regular cigarettes.
Cross-sectional survey data from students aged 13-19 years from Piotrkowski
district, Poland were analyzed. Among the sample of 4050 students, 3552
respondents completed anonymous, confidential, self-administered questionnaire
adapted from the Global Youth Tobacco Survey (GYTS). The study results indicate
that the students perceived slim cigarettes and menthol cigarettes as less
harmful, which is in line with the message created by tobacco companies. On the
other hand, less popular products such as water pipes and smokeless tobacco were
considered as more harmful. The current study indicates insufficient and
misleading perception of harmfulness of different tobacco/nicotine products
available on the Polish market. Simultaneously, there is insufficient countrywide
public health education in this matter. Preventive measures are necessary to
discourage young people from smoking uptake and to ensure that potential
consumers can, based on objective data, make informed decisions about cigarettes
and non-cigarette tobacco products.
PMID- 27608035
TI - Predicting Avian Influenza Co-Infection with H5N1 and H9N2 in Northern Egypt.
AB - Human outbreaks with avian influenza have been, so far, constrained by poor viral
adaptation to non-avian hosts. This could be overcome via co-infection, whereby
two strains share genetic material, allowing new hybrid strains to emerge.
Identifying areas where co-infection is most likely can help target spaces for
increased surveillance. Ecological niche modeling using remotely-sensed data can
be used for this purpose. H5N1 and H9N2 influenza subtypes are endemic in
Egyptian poultry. From 2006 to 2015, over 20,000 poultry and wild birds were
tested at farms and live bird markets. Using ecological niche modeling we
identified environmental, behavioral, and population characteristics of H5N1 and
H9N2 niches within Egypt. Niches differed markedly by subtype. The subtype niches
were combined to model co-infection potential with known occurrences used for
validation. The distance to live bird markets was a strong predictor of co
infection. Using only single-subtype influenza outbreaks and publicly available
ecological data, we identified areas of co-infection potential with high accuracy
(area under the receiver operating characteristic (ROC) curve (AUC) 0.991).
PMID- 27608036
TI - Analysis of the Prevalence of HTLV-1 Proviral DNA in Cervical Smears and
Carcinomas from HIV Positive and Negative Kenyan Women.
AB - The oncogenic retrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is
endemic in some countries although its prevalence and relationship with other
sexually transmitted infections in Sub-Saharan Africa is largely unknown. A novel
endpoint PCR method was used to analyse the prevalence of HTLV-1 proviral DNA in
genomic DNA extracted from liquid based cytology (LBC) cervical smears and
invasive cervical carcinomas (ICCs) obtained from human immunodeficiency virus
positive (HIV+ve) and HIV-negative (HIV-ve) Kenyan women. Patient
sociodemographic details were recorded by structured questionnaire and these data
analysed with respect to HIV status, human papillomavirus (HPV) type
(Papilocheck((r))) and cytology. This showed 22/113 (19.5%) of LBC's from HIV+ve
patients were positive for HTLV-1 compared to 4/111 (3.6%) of those from HIV-ve
women (p = 0.0002; odds ratio (OR) = 6.42 (2.07-26.56)). Only 1/37 (2.7%) of
HIV+ve and none of the 44 HIV-ve ICC samples were positive for HTLV-1. There was
also a significant correlation between HTLV-1 infection, numbers of sexual
partners (p < 0.05) and smoking (p < 0.01). Using this unique method, these data
suggest an unexpectedly high prevalence of HTLV-1 DNA in HIV+ve women in this
geographical location. However, the low level of HTLV-1 detected in HIV+ve ICC
samples was unexpected and the reasons for this are unclear.
PMID- 27608038
TI - Rural-Urban Differences of Dietary Patterns, Overweight, and Bone Mineral Status
in Chinese Students.
AB - China is an urban and rural social model country. In the past three decades, the
developing speed of rural areas has been much slower than urban areas, which may
lead to the differences in dietary patterns. This study aimed to investigate the
disparities of dietary structures from urban and rural children, and to analyze
the effects of different dietary patterns on their adverse outcome. Among 1590
students, aged 11 years to 17 years, from primary and middle schools, a cross
sectional study was conducted. There were three dietary patterns recognized:
Westernization structure, meat diet structure, and Western and Chinese structure.
Compared with rural students, more urban students were in the highest categories
of the whole dietary patterns (p < 0.001). Overweight/obesity and central
adiposity were more prevailing among urban students, while rural students had a
more prevailing risk of bone fracture (p < 0.05). Through the adjustment for all
confounding factors, the Westernization structure could increase the risk of
overweight/obesity and central adiposity, the meat structure could increase the
risk of elevated blood pressure/hypertension, while the risk of low bone mineral
quality could be reduced by the Chinese and Western structure. In conclusion, a
rural-urban disparity in dietary patterns was found in our study, and different
dietary patterns were associated with the risk of some adverse outcomes.
Therefore, there were different prevalences of the adverse outcomes between rural
and urban students.
PMID- 27608037
TI - Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical
Markers Related to Cardiometabolic Risk in Saudi Subjects.
AB - BACKGROUND: This study aimed to examine the relationship between changes in
systemic vitamin B12 concentrations with pro-inflammatory cytokines,
anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi
population. METHODS: A total of 364 subjects (224 children, age: 12.99 +/- 2.73
(mean +/- SD) years; BMI: 20.07 +/- 4.92 kg/m2 and 140 adults, age: 41.87 +/-
8.82 years; BMI: 31.65 +/- 5.77 kg/m2) were studied. Fasting blood,
anthropometric and biochemical data were collected. Serum cytokines were
quantified using multiplex assay kits and B12 concentrations were measured using
immunoassay analyzer. RESULTS: Vitamin B12 was negatively associated with TNF
alpha (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r =
0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively
associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p <
0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively
associated with TNF-alpha (r = -0.242, p < 0.01) while positively associated with
resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor
for circulating vitamin B12 in all subjects (r2 = -0.17, p < 0.05) and in
children (r2 = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12
in adults (r2 = -0.78, p < 0.05). CONCLUSIONS: Serum vitamin B12 concentrations
were associated with pro-inflammatory cytokines and biochemical markers of
cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations
may lower inflammation-induced cardiometabolic risk in the Saudi adult
population.
PMID- 27608039
TI - Associations between Dietary Patterns, ADRbeta2 Gln27Glu and ADRbeta3 Trp64Arg
with Regard to Serum Triglyceride Levels: J-MICC Study.
AB - Interactions between dietary patterns and 2 beta-adrenergic receptor (ADRbeta)
gene polymorphisms (ADRbeta2 Gln27Glu and ADRbeta3 Trp64Arg) were examined with
regard to the effects on serum triglyceride levels. The cross-sectional study
comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi
Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using
a multiplex polymerase chain reaction-based invader assay. We used 46 items from
a validated short food frequency questionnaire and examined major dietary
patterns by factor analysis. We identified four dietary patterns: healthy,
Western, seafood and bread patterns. There was no significant association between
any dietary pattern and serum triglyceride levels. After a separate genotype
based analysis, significant interactions between ADRbeta3 Trp64Arg genotype and
the bread pattern (p for interaction = 0.01) were associated with serum
triglyceride levels; specifically, after adjusting for confounding factors, Arg
allele carriers with the bread pattern had lower serum triglycerides (p for trend
= 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed
no association with serum triglycerides (p for trend = 0.55). Interactions
between other dietary patterns and ADRbeta polymorphisms were not significant for
serum triglyceride levels. Our findings suggest that ADRbeta3 polymorphism
modifies the effects of the bread pattern on triglyceride levels.
PMID- 27608040
TI - Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics.
AB - Evidence from numerous observational and clinical studies suggest that
polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in
tea, chocolate and grapes, and isoflavones in soy products reduce the risk of
breast cancer. A dietary food pattern naturally rich in polyphenols is the
Mediterranean diet and evidence suggests those of Mediterranean descent have a
lower breast cancer incidence. Whilst dietary polyphenols have been the subject
of breast cancer risk-reduction, this review will focus on the clinical effects
of polyphenols on reducing recurrence. Overall, we recommend breast cancer
patients consume a diet naturally high in flavonol polyphenols including tea,
vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings
of vegetables and fruit daily appear protective. Moderate soy protein consumption
(5-10 g daily) and the Mediterranean dietary pattern show the most promise for
breast cancer patients. In this review, we present an overview of clinical trials
on supplementary polyphenols of dietary patterns rich in polyphenols on breast
cancer recurrence, mechanistic data, and novel delivery systems currently being
researched.
PMID- 27608041
TI - miR-541 Contributes to Microcystin-LR-Induced Reproductive Toxicity through
Regulating the Expression of p15 in Mice.
AB - Microcystin-leucine arginine (MC-LR) is a harmful cyanotoxin produced by
cyanobacteria. MC-LR can exert endocrine-disrupting activities in many organisms.
We have previously demonstrated that MC-LR exerts both acute and chronic
reproductive toxicity in male mice, resulting in a decline in sperm quality and
damage to testicular structure. Moreover, we also observed extensive alterations
in a panel of microRNAs in spermatogonial cells after exposure to MC-LR. In this
study, we have confirmed that miR-541 was significantly increased both in GC-1
cells (in vitro) and in mouse testes (in vivo) after exposure to MC-LR. Our data
support that p15 was the target gene of miR-541. Increase in miR-541 led to a
reduction of p15 and murine double minute2 (MDM2), promoting the activation of
p53 signaling and MC-LR-mediated cell apoptosis. Moreover, cells responded to MC
LR with reduced viability and increased apoptosis. Consistently, inhibiting miR
541 could upregulate the expression of p15 and MDM2, resulting in the
downregulation of phospho-p53. Downregulation of miR-541 promoted cell viability
by reducing MC-LR-induced cell apoptosis. In conclusion, we demonstrate here a
crucial role for miR-541 in MC-LR-induced toxic effects on the reproductive
system, in an attempt to provide a rational strategy for the diagnosis and
treatment of MC-LR-induced impairment in the reproductive system.
PMID- 27608042
TI - The Contents of Ustiloxins A and B along with Their Distribution in Rice False
Smut Balls.
AB - Ustiloxins are cyclopeptide mycotoxins isolated from rice false smut balls
(FSBs), the ball-like colonies transformed from the individual grains through the
filament infection by the fungal pathogen Villosiclava virens. There were no
obvious relations between ustiloxin content and any of the collection areas,
collection times, or average weight of each FSB. The rice false smut balls at
early, middle, and late maturity stages were respectively divided into different
parts (glume, chlamydospores, mycelia, and pseudoparenchyma). The highest content
of ustiloxins A and B of rice FSBs was found at the early maturity stage. Both
ustiloxins A and B were mainly distributed in the middle layer containing mycelia
and immature chlamydospores of the FSBs. When the rice FSBs were at the early
maturity stage, the total yield of ustiloxins A and B in the middle layer of each
ball was 48.3 ug, which was 3.20-fold of the yield (15.1 ug) of the inner part of
the ball. The rice FSBs at the early maturity stage are the appropriate materials
for the production of ustiloxins A and B.
PMID- 27608043
TI - Antibiotic Treatment in End-of-Life Cancer Patients-A Retrospective Observational
Study at a Palliative Care Center in Sweden.
AB - BACKGROUND: The aim of this study was to elucidate whether palliative cancer
patients benefit from antibiotic treatment in the last two weeks of life when an
infection is suspected. METHOD: We reviewed medical records from 160 deceased
palliative cancer patients that had been included in previous studies on vitamin
D and infections. Patients treated with antibiotics during the last two weeks of
life were identified and net effects of treatment (symptom relief) and possible
adverse events were extracted from medical records. RESULTS: Seventy-nine
patients (49%) had been treated with antibiotics during the last two weeks in
life. In 37% (n = 29), the treatment resulted in evident symptom relief and among
these 50% had a positive bacterial culture, 43% had a negative culture and in 7%
no culture was taken. Among the patients with no or unknown effect of
antibiotics, 50% had a positive culture. When the indication for antibiotic
treatment was to avoid or treat sepsis, symptom relief was achieved in 50% of the
patients (n = 19). Only 4% (n = 3) of the patients experienced adverse events of
the treatment (diarrhea, nausea). CONCLUSIONS: Treating infections with
antibiotics in the last weeks of life may improve the quality of life for
palliative cancer patients, especially if sepsis is suspected or confirmed.
According to our results, the beneficial effects outweigh the potentially
negative outcomes.
PMID- 27608044
TI - Evidence Supporting the Uptake and Genomic Incorporation of Environmental DNA in
the "Ancient Asexual" Bdelloid Rotifer Philodina roseola.
AB - Increasing evidence suggests that bdelloid rotifers regularly undergo horizontal
gene transfer, apparently as a surrogate mechanism of genetic exchange in the
absence of true sexual reproduction, in part because of their ability to
withstand desiccation. We provide empirical support for this latter hypothesis
using the bdelloid Philodina roseola, which we demonstrate to readily internalize
environmental DNA in contrast to a representative monogonont rotifer (Brachionus
rubens), which, like other monogononts, is facultative sexual and cannot
withstand desiccation. In addition, environmental DNA that was more similar to
the host DNA was retained more often and for a longer period of time. Indirect
evidence (increased variance in the reproductive output of the untreated F1
generation) suggests that environmental DNA can be incorporated into the genome
during desiccation and is thus heritable. Our observed fitness effects agree with
sexual theory and also occurred when the animals were desiccated in groups
(thereby acting as DNA donors), but not individually, indicating the mechanism
could occur in nature. Thus, although DNA uptake and its genomic incorporation
appears proximally related to anhydrobiosis in bdelloids, it might also
facilitate accidental genetic exchange with closely related taxa, thereby
maintaining higher levels of genetic diversity than is otherwise expected for
this group of "ancient asexuals".
PMID- 27608045
TI - Dynamic Contrast-Enhanced CT in Patients with Pancreatic Cancer.
AB - The aim of this systematic review is to provide an overview of the use of Dynamic
Contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic
cancer. This study was composed according to the PRISMA guidelines 2009. The
literature search was conducted in PubMed, Cochrane Library, EMBASE, and Web of
Science databases to identify all relevant publications. The QUADAS-2 tool was
implemented to assess the risk of bias and applicability concerns of each
included study. The initial literature search yielded 483 publications. Thirteen
articles were included. Articles were categorized into three groups: nine
articles concerning primary diagnosis or staging, one article about tumor
response to treatment, and three articles regarding scan techniques. In exocrine
pancreatic tumors, measurements of blood flow in eight studies and blood volume
in seven studies were significantly lower in tumor tissue, compared with
measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue
in control groups of healthy volunteers. The studies were heterogeneous in the
number of patients enrolled and scan protocols. Perfusion parameters measured and
analyzed by DCE-CT might be useful in the investigation of characteristic
vascular patterns of exocrine pancreatic tumors. Further clinical studies are
desired for investigating the potential of DCE-CT in pancreatic tumors.
PMID- 27608047
TI - Membrane Technology for the Recovery of Lignin: A Review.
AB - Utilization of renewable resources is becoming increasingly important, and only
sustainable processes that convert such resources into useful products can
achieve environmentally beneficial economic growth. Wastewater from the pulp and
paper industry is an unutilized resource offering the potential to recover
valuable products such as lignin, pigments, and water [1]. The recovery of lignin
is particularly important because it has many applications, and membrane
technology has been investigated as the basis of innovative recovery solutions.
The concentration of lignin can be increased from 62 to 285 g?L(-1) using
membranes and the recovered lignin is extremely pure. Membrane technology is also
scalable and adaptable to different waste liquors from the pulp and paper
industry.
PMID- 27608046
TI - T-Regulatory Cells and Vaccination "Pay Attention and Do Not Neglect Them":
Lessons from HIV and Cancer Vaccine Trials.
AB - Efficient vaccines are characterized by the establishment of long-lived memory T
cells, including T-helper (effectors and follicular) and T-regulatory cells
(Tregs). While the former induces cytotoxic or antibody responses, the latter
regulates immune responses by maintaining homeostasis. The role of Tregs in
inflammatory conditions is ambiguous and their systematic monitoring in
vaccination along with effector T-cells is not instinctive. Recent studies from
the cancer field clearly showed that Tregs suppress vaccine-induced immune
responses and correlate with poor clinical benefit. In HIV infection, Tregs are
needed during acute infection to preserve tissue integrity from an overwhelmed
activation, but are not beneficial in chronic infection as they suppress anti-HIV
responses. Current assays used to evaluate vaccine-induced specific responses are
limited as they do not take into account antigen-specific Tregs. However, new
assays, such as the OX40 assay, which allow for the simultaneous detection of a
full range of Th-responses including antigen-specific Tregs responses, can
overcome these issues. In this review article we will revise the role of Tregs in
vaccination and review the recent work performed in the field, including the
available tools to monitor them, from novel assays to humanized mouse models.
PMID- 27608048
TI - Knockdown of WHIRLY1 Affects Drought Stress-Induced Leaf Senescence and Histone
Modifications of the Senescence-Associated Gene HvS40.
AB - The plastid-nucleus located protein WHIRLY1 has been described as an upstream
regulator of leaf senescence, binding to the promoter of senescence-associated
genes like HvS40. To investigate the impact of WHIRLY1 on drought stress-induced,
premature senescence, transgenic barley plants with an RNAi-mediated knockdown of
the HvWHIRLY1 gene were grown under normal and drought stress conditions. The
course of leaf senescence in these lines was monitored by physiological
parameters and studies on the expression of senescence- and drought stress
related genes. Drought treatment accelerated leaf senescence in WT plants,
whereas WHIRLY 1 knockdown lines (RNAi-W1) showed a stay-green phenotype.
Expression of both senescence-associated and drought stress-responsive genes, was
delayed in the transgenic plants. Notably, expression of transcription factors of
the WRKY and NAC families, which are known to function in senescence- and stress
related signaling pathways, was affected in plants with impaired accumulation of
WHIRLY1, indicating that WHIRLY1 acts as an upstream regulator of drought stress
induced senescence. To reveal the epigenetic indexing of HvS40 at the onset of
drought-induced senescence in WT and RNAi-W1 lines, stress-responsive loading
with histone modifications of promoter and coding sequences of HvS40 was analyzed
by chromatin immunoprecipitation and quantified by qRT-PCR. In the wildtype, the
euchromatic mark H3K9ac of the HvS40 gene was low under control conditions and
was established in response to drought treatment, indicating the action of
epigenetic mechanisms in response to drought stress. However, drought stress
caused no significant increase in H3K9ac in plants impaired in accumulation of
WHIRLY1. The results show that WHIRLY1 knockdown sets in motion a delay in
senescence that involves all aspects of gene expression, including changes in
chromatin structure.
PMID- 27608049
TI - Alopecia areata totalis and universalis: a multicenter review of 132 patients in
Spain.
AB - BACKGROUND: Alopecia areata totalis (AAT) and universalis (AAU) pose a
therapeutic challenge. OBJECTIVE: To describe the clinical and epidemiological
features, therapeutic response and prognostic factors in a large series of
patients diagnosed with AAT and AAU. METHODS: This retrospective multicenter
study included patients diagnosed with AAT/AAU with a minimum follow-up of 12
months. Response was assessed based on the regrowth of scalp hair. RESULTS: In
all, 132 patients (92 women and 40 men) - 80 (61%) diagnosed with AAU and 52
(39%) diagnosed with AAT - were included. The median time between the
presentation of alopecia areata (AA) and the development of extensive AA was 1
year and it was less than 4 years in 121 patients (91%). There was an initial
response to treatment in 64% of patients, although only 14% presented a
persistent response. Adverse side effects from the medications used were detected
in 33% of patients. The prognostic factors associated with poor response were the
presence of AAU and a positive family history of AA. CONCLUSIONS: Treatment of
AAT and AAU is challenging. Although an initial regrowth may be achieved, the
duration of response is usually short. There were no significant differences on
the effectiveness or duration of response between the various systemic therapies.
PMID- 27608050
TI - "They are looking just the same": Antiretroviral treatment as social danger in
rural Malawi.
AB - Research on the social impact of ART pivots on questions of individual adherence
and community acceptability of treatment programmes. In this paper we examine
unexpected and unintended consequences of the scale-up of treatment in rural
Malawi, using a unique dataset of more than 150 observational journals from three
sites, spanning 2010 to 2013, focusing on men's everyday conversations. Through
thematic content analysis, we explore the emerging perception that the widespread
availability of ART constitutes a form of social danger, as treatment makes it
difficult to tell who does or does not have AIDS. This ambiguity introduced
through ART is interpreted as putting individuals at risk, because it is no
longer possible to tell who might be infected - indeed, the sick now look
healthier and "plumper" than the well. This ambivalence over the social impact of
ART co-exists with individual demand for and appreciation of the benefits of
treatment.
PMID- 27608053
TI - Spontaneous Devascularization and Detachment of Optic Nerve Hemangioblastoma in a
Patient With Von Hippel-Lindau Disease.
PMID- 27608054
TI - Incarceration of Lens Capsular Material in a Tube Shunt in an Aphakic,
Vitrectomized Infant Eye.
PMID- 27608055
TI - Macular Retinal Cavernous Hemangioma Associated With Congenital Retinal
Macrovessel.
PMID- 27608056
TI - Demonstration of Choroidal Neovascularization Associated With an Intraretinal
Lesion on Indocyanine Green Angiography Independent of Choroidal New Vessel on
Optical Coherence Tomography.
PMID- 27608057
TI - Thin tungsten telluride layer preparation by thermal annealing.
AB - We report a simple method to prepare a thin Tungsten Telluride (WTe2) flake with
accurate thickness control, which allows preparing and studying this two
dimensional material conveniently. First, the WTe2 flake, which is relatively
thick due to its strong interlayer van der Waals forces, is obtained by a
conventional mechanical exfoliation method. Then, the exfoliated flake is
annealed at 600 degrees C under a constant Ar protecting flow. Raman and atomic
force spectroscopy characterizations demonstrate that thermal annealing can
effectively thin down the WTe2 flake and retain its original lattice structure,
though its surface smoothness is slightly deteriorated. Additionally,
systematical study indicates that the thinning process strongly depends on the
initial thickness of the WTe2 flake before annealing: the thinning rate increases
from 0.12 nm min(-1) to 0.36 nm min(-1) as the initial thickness increases from
10 nm to 45 nm, while the roughness of the final product also increases with the
increase of its initial thickness. However, the method fails when it is applied
to WTe2 flakes thicker than 100 nm, resulting in uneven or burnt surface, which
is possibly caused by big cavities formed by a large amount of defects gathered
at the top surface.
PMID- 27608058
TI - Interpreting Database Studies-Reply.
PMID- 27608059
TI - Isotope-dilution method for the determination of 1-vinyl-2-pyrrolidone
mercapturic acid as a potential human biomarker for 1-vinyl-2-pyrrolidone via
online SPE ESI-LC/MS/MS in negative ionization mode.
AB - We established and validated a specific and sensitive analytical method for the
determination of 1-vinyl-2-pyrrolidone (VP) as 1-vinyl-2-pyrrolidone-mercapturic
acid (VPMA) in urine using an electrospray liquid chromatography tandem mass
spectrometry (ESI-LC/MS/MS) column switching method. An online solid phase
extraction (SPE) for sample cleanup was performed by column switching to a
restricted access material and back-flushing to the analytical column. A
Phenomenex Luna C8 column was used for sample separation (150mm; ID 4,6mm; 3MUm).
D4-VPMA served as an isotope labeled internal standard and was detected in
negative multiple-reaction monitoring (MRM) mode. The Limit of quantification
(LOQ) for VPMA was 1.5MUg/L, the intra-day precision of three concentrations
(2MUg/L, 75MUg/L and 400MUg/L) of spiked urine samples ranged from 2.7 to 7.3%,
the inter-day precision from 3.4 to 14.4%. The accuracy ranged from 6.2 to 9.0%,
for the intra-day experiments and from 0.3 to 6.9% for the inter-day experiments.
The method was applied to urines of Sprague-Dawley rats exposed to VP as a proof
of principle of VPMA as a potential biomarker.
PMID- 27608060
TI - Dietary assessment is a critical element of health research - Perspective from
the Partnership for Advancing Nutritional and Dietary Assessment in Canada.
AB - Challenges and complexities associated with assessing dietary intakes are
numerous, but not insurmountable. This opinion paper from Canadian researchers
draws attention to the importance of building capacity and providing funding
opportunities for research in dietary assessment methods in Canada and elsewhere.
Such strategies would contribute to a better understanding of the roles played by
diet in human health and better translation of this information into the most
meaningful and effective dietary guidelines, policies, and interventions.
PMID- 27608061
TI - Distinct Mitochondrial Disturbance in CD4+T and CD8+T Cells From HIV-Infected
Patients.
AB - BACKGROUND: Mitochondrial dysfunction has frequently been found in HIV-infected
patients regardless of whether they received antiretroviral therapy (ART).
Accumulating evidence suggests that HIV-infected patients exhibit marked changes
in mitochondrial membrane potential (MMP), reactive oxygen species (ROS)
accumulation, adenosine triphosphate generation, mitochondrial mass (MM),
mitochondrial DNA, etc. However, mitochondrial toxicity in CD4T and CD8T cells
caused by different levels of HIV progression and ART is poorly understood.
METHODS: Blood samples were obtained from 97 ART-naive HIV-infected patients with
different CD4T cell counts, 97 nucleoside-reverse transcriptase inhibitors
exposed HIV-infected patients, and 25 HIV-negative subjects. MMP, ROS, and MM in
CD4T and CD8T cells were assessed by flow cytometry. RESULTS: In healthy
subjects, the levels of MMP and MM in CD4T cells were higher than those in CD8T
cells. HIV infection led to an increase in MM in CD4T and CD8T cells, but mainly
influenced MMP in CD8T cells and ROS accumulation in CD4T cells. MM in CD4T and
CD8T cells gradually increased after the loss of CD4T cells. Although the dynamic
changes in MMP in CD4T cells were different from those in CD8T cells during
highly active ART, MM in both CD4T and CD8T cells was significantly decreased
after 2 years of therapy, but increased again after 3 years. CONCLUSIONS: HIV
infection and antiretroviral therapy both led to mitochondrial disturbances in
CD4T cells and CD8T cells; however, the abnormal changes in mitochondrial
parameters in CD4+T cells were different from those in CD8T cells caused by HIV
infection and antiretroviral therapy.
PMID- 27608062
TI - Patch Test Negative Generalized Dermatitis.
AB - Allergic contact dermatitis is a common condition in dermatology. Patch testing
is the criterion standard for diagnosis. However, dermatitis is not always caused
by an allergen, and patch testing does not identify a culprit in every patient.
Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3
body sites, is often encountered in dermatology practice, especially patch test
referral centers. Management for patients with generalized dermatitis who are
patch test negative is challenging. The purpose of this article is to outline an
approach to this challenging scenario and summarize the paucity of existing
literature on patch test negative generalized dermatitis.
PMID- 27608063
TI - Return to Work for Nurses With Hand Dermatitis.
AB - BACKGROUND: Occupational skin disease is common in healthcare workers. If the
healthcare worker develops moderate to severe dermatitis, return to work (RTW)
may be challenging. OBJECTIVES: The study objectives were to review the impact of
an RTW program on the work status of nurses with occupational hand dermatitis and
to identify successful intervention methods and strategies. METHODS: Nurses who
received RTW services at a tertiary occupational medicine clinic were identified,
and information related to their diagnosis and RTW was abstracted from their
charts. RESULTS: Eighteen nurses with irritant hand dermatitis who received RTW
services were identified. Twelve nurses (67%) were performing administrative
duties because of their skin condition when admitted to the RTW program, and
others were performing patient care with modifications. A graduated RTW trial was
commonly implemented with optimized skin care management and monitoring by
physicians and the RTW coordinator. Upon discharge, 14 nurses (78%) had returned
to their nursing roles with direct patient care, 3 (17%) were working as nurses
in non-patient care roles, and 1 (6%) was on permanent disability. CONCLUSIONS: A
graduated RTW trial to reduce cumulative irritant exposure is a crucial strategy
to facilitate nurses' transition back to work and to maintain direct patient care
nursing roles.
PMID- 27608064
TI - Proposed ICDRG Classification of the Clinical Presentation of Contact Allergy.
AB - The International Contact Dermatitis Research Group proposes a classification for
the clinical presentation of contact allergy. The classification is based
primarily on the mode of clinical presentation. The categories are direct
exposure/contact dermatitis, mimicking or exacerbation of preexisting eczema,
multifactorial dermatitis including allergic contact dermatitis, by proxy,
mimicking angioedema, airborne contact dermatitis, photo-induced contact
dermatitis, systemic contact dermatitis, noneczematous contact dermatitis,
contact urticaria, protein contact dermatitis, respiratory/mucosal symptoms, oral
contact dermatitis, erythroderma/exfoliative dermatitis, minor forms of
presentation, and extracutaneous manifestations.
PMID- 27608065
TI - para-Phenylenediamine Hypersensitivity: A Report From Budapest, Hungary, 2007
2014.
AB - BACKGROUND: para-Phenylenediamine (PPD) is a potent allergen with frequent
exposure through use of hair dyes or henna tattoos. OBJECTIVES: We wished to
determine if prevalence of PPD sensitivity is changing through time as trends in
its use change. PATIENTS: A total of 3631 patients were patch tested
consecutively with the environmental standard series between 2007 and 2014 to map
the prevalence of PPD sensitivity and its distribution according to age, sex, and
diagnosis. RESULTS: Two hundred nine patients (5.75%) were proven to be PPD
sensitive. Most PPD-sensitive patients were approximately in their 60s in 2007,
whereas in 2014, they were in their 20s and 30s. In 2014, 61.1% of the patients
were younger than 35 years and 50% were younger than 25 years. Of 209 PPD
sensitive patients, 32.5% had present relevance related to hair dyeing and
eyebrow or eyelash coloring procedures. All affected male patients were
hairdressers. Adverse reaction to henna was detected in only 1 case after henna
hair dye use. CONCLUSIONS: The 5.75% prevalence of PPD sensitization in our study
was higher compared with that in the European data. It is alarming that PPD
hypersensitivity occurred even among teenagers. This may be mainly explained by
hair dyeing at an early age.
PMID- 27608066
TI - Neisseria gonorrhoeae isolated from an unexpected site.
AB - We describe a case of Neisseria gonorrhoeae isolated from a nipple piercing wound
in a homosexual man with pharyngeal gonococcal carriage.
PMID- 27608067
TI - Reducing prospective memory error and costs in simulated air traffic control:
External aids, extending practice, and removing perceived memory requirements.
AB - In air traffic control (ATC), forgetting to perform deferred actions-prospective
memory (PM) errors-can have severe consequences. PM demands can also interfere
with ongoing tasks (costs). We examined the extent to which PM errors and costs
were reduced in simulated ATC by providing extended practice, or by providing
external aids combined with extended practice, or by providing external aids
combined with instructions that removed perceived memory requirements.
Participants accepted/handed-off aircraft and detected conflicts. For the PM
task, participants were required to substitute alternative actions for routine
actions when accepting aircraft. In Experiment 1, when no aids were provided, PM
errors and costs were not reduced by practice. When aids were provided, costs
observed early in practice were eliminated with practice, but residual PM errors
remained. Experiment 2 provided more limited practice with aids, but instructions
that did not frame the PM task as a "memory" task led to high PM accuracy without
costs. Attention-allocation policies that participants set based on expected PM
demands were modified as individuals were increasingly exposed to reliable aids,
or were given instructions that removed perceived memory requirements. These
findings have implications for the design of aids for individuals who monitor
multi-item dynamic displays. (PsycINFO Database Record
PMID- 27608069
TI - Face-off: A new identification procedure for child eyewitnesses.
AB - In 2 experiments, we introduce a new "face-off" procedure for child eyewitness
identifications. The new procedure, which is premised on reducing the stimulus
set size, was compared with the showup and simultaneous procedures in Experiment
1 and with modified versions of the simultaneous and elimination procedures in
Experiment 2. Several benefits of the face-off procedure were observed: it was
significantly more diagnostic than the showup procedure; it led to significantly
more correct rejections of target-absent lineups than the simultaneous procedures
in both experiments, and it led to greater information gain than the modified
elimination and simultaneous procedures. The face-off procedure led to
consistently more conservative responding than the simultaneous procedures in
both experiments. Given the commonly cited concern that children are too lenient
in their decision criteria for identification tasks, the face-off procedure may
offer a concrete technique to reduce children's high choosing rates. (PsycINFO
Database Record
PMID- 27608070
TI - Fluoride Removal from Brackish Groundwaters by Constant Current Capacitive
Deionization (CDI).
AB - Charging capacitive deionization (CDI) at constant voltage (CV) produces an
effluent stream in which ion concentrations vary with time. Compared to CV,
charging CDI at constant current (CC) has several advantages, particularly a
stable and adjustable effluent ion concentration. In this work, the feasibility
of removing fluoride from brackish groundwaters by single-pass constant-current
(SPCC) CDI in both zero-volt and reverse-current desorption modes was
investigated and a model developed to describe the selective electrosorption of
fluoride and chloride. It was found that chloride is preferentially removed from
the bulk solution during charging. Both experimental and theoretical results are
presented showing effects of operating parameters, including
adsorption/desorption current, pump flow rate and fluoride/chloride feed
concentrations, on the effluent fluoride concentration, average fluoride
adsorption rate and water recovery. Effects of design parameters are also
discussed using the validated model. Finally, we describe a possible CDI assembly
in which, under appropriate conditions, fluoride water quality targets can be
met. The model developed here adequately describes the experimental results
obtained and shows how change in the selected system design and operating
conditions may impact treated water quality.
PMID- 27608068
TI - The effects of curiosity-evoking events on activity enjoyment.
AB - Whereas prior literature has studied the positive effects of curiosity-evoking
events that are integral to focal activities, we explore whether and how a
curiosity-evoking event that is incidental to a focal activity induces negative
outcomes for enjoyment. Four experiments and 1 field study demonstrate that
curiosity about an event that is incidental to an activity in which individuals
are engaged, significantly affects enjoyment of a concurrent activity. The reason
why is that curiosity diverts attention away from the concurrent activity and
focuses attention on the curiosity-evoking event. Thus, curiosity regarding an
incidental event decreases enjoyment of a positive focal activity but increases
enjoyment of a negative focal activity.
PMID- 27608132
TI - Flavonoids and a Limonoid from the Fruits of Citrus unshiu and Their Biological
Activity.
AB - The fruits of Citrus unshiu are one of the most popular and most enjoyed fruits
in Korea. As we continue to seek for bioactive metabolites from Korean natural
resources, our study on the chemical constituents of the fruits of C. unshiu
resulted in the isolation of a new flavonoid glycoside, limocitrunshin 1, along
with seven other flavonoids 2-8 and a limonoid 9. All structures were identified
by spectroscopic methods, namely 1D and 2D NMR, including HSQC, HMBC, and (1)H
(1)H COSY experiments, HRMS, and other chemical methods. Compounds 3, 5, and 9
are reported to be isolated from this fruit for the first time. The isolated
compounds were applied to activity tests to verify their inhibitory effects on
inflammation and nephrotoxicity. Compounds 6 and 9 showed the most potent
inhibitory activity on renal cell damage and nitric oxide production,
respectively. Thus, the fruits of C. unshiu could serve as a valuable natural
source of bioactive components with health benefits for potential application in
functional foods.
PMID- 27608133
TI - A systems biology approach for elucidating the interaction of curcumin with
Fanconi anemia FANC G protein and the key disease targets of leukemia.
AB - Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of
malignancies including acute myeloid leukemia and squamous cell carcinoma. There
is a constant search out of new potential therapeutic molecule to combat this
disorder. In most cases, patients with FA develop haematological malignancies
with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs
which can efficiently block the pathways of both these disorders can be an ideal
and novel strategy to treat FA. The curcumin, a natural compound obtained from
turmeric is an interesting therapeutic molecule as it has been reported in the
literature to combat both FA as well as leukemia. However, its complete mechanism
is not elucidated. Herein, a systems biology approach for elucidating the
therapeutic potential of curcumin against FA and leukemia is investigated by
analyzing the computational molecular interactions of curcumin ligand with FANC G
of FA and seven other key disease targets of leukemia. The proteins namely DOT1L,
farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK
2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid
receptor alpha (RARA) were chosen as disease targets for leukemia and modeled
structure of FANC G protein as the disease target for FA. The docking
investigations showed that curcumin had a very high binding affinity of -8.1
kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine
kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed
that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k
cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage
similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a
clue to understand the structural relationships to an extent and to predict the
binding affinity. This investigation shows that curcumin effectively interacts
with the disease targets of both FA and leukemia.
PMID- 27608134
TI - Development and validation of the trait and state versions of the Post-Event
Processing Inventory.
AB - BACKGROUND: Post-event processing (PEP) refers to negative and prolonged
rumination following anxiety-provoking social situations. Although there are
scales to assess PEP, they are situation-specific, some targeting only public
speaking situations. Furthermore, there are no trait measures to assess the
tendency to engage in PEP. OBJECTIVES: The purpose of this research was to create
a new measure of PEP, the Post-Event Processing Inventory (PEPI), which can be
employed following all types of social situations and includes both trait and
state forms. DESIGN AND METHOD: Over two studies (study 1, N = 220; study 2, N =
199), we explored and confirmed the factor structure of the scale with student
samples. RESULTS: For each form of the scale, we found and confirmed that a
higher-order, general PEP factor could be inferred from three sub-domains
(intensity, frequency, and self-judgment). We also found preliminary evidence for
the convergent, concurrent, discriminant/divergent, incremental, and predictive
validity for each version of the scale. Both forms of the scale demonstrated
excellent internal consistency and the trait form had excellent two-week test
retest reliability. CONCLUSION: Given the utility and versatility of the scale,
the PEPI may provide a useful alternative to existing measures of PEP and
rumination.
PMID- 27608135
TI - Localized surface plasmon resonance frequency tuning in highly doped InAsSb/GaSb
one-dimensional nanostructures.
AB - We report a detailed analysis of the influence of the doping level and nanoribbon
width on the localized surface plasmon resonance (LSPR) by means of reflectance
measurements. The plasmonic system, based on one-dimensional periodic gratings of
highly Si-doped InAsSb/GaSb semiconductor nanostructures, is fabricated by a
simple, accurate and large-area technique fabrication. Increasing the doping
level blueshifts the resonance peak while increasing the ribbon width results in
a redshift, as confirmed by numerical simulations. This provides an efficient
means of fine-tuning the LSPR properties to a target purpose of between 8-20 MUm
(1250-500 cm(-1)). Finally, we show surface plasmon resonance sensing to
absorbing polymer layers. We address values of the quality factor, sensitivity
and figure of merit of 16 700 nm RIU(-1) and 2.5, respectively. These results
demonstrate Si-doped InAsSb/GaSb to be a low-loss/high sensitive material making
it very promising for the development of biosensing devices in the mid-infrared.
PMID- 27608136
TI - Artificial Synapses Based on in-Plane Gate Organic Electrochemical Transistors.
AB - Realization of biological synapses using electronic devices is regarded as the
basic building blocks for neuromorphic engineering and artificial neural network.
With the advantages of biocompatibility, low cost, flexibility, and compatible
with printing and roll-to-roll processes, the artificial synapse based on organic
transistor is of great interest. In this paper, the artificial synapse simulation
by ion-gel gated organic field-effect transistors (FETs) with poly(3
hexylthiophene) (P3HT) active channel is demonstrated. Key features of the
synaptic behaviors, such as paired-pulse facilitation (PPF), short-term
plasticity (STP), self-tuning, the spike logic operation, spatiotemporal
dentritic integration, and modulation are successfully mimicked. Furthermore, the
interface doping processes of electrolyte ions between the active P3HT layer and
ion gels is comprehensively studied for confirming the operating processes
underlying the conductivity and excitatory postsynaptic current (EPSC) variations
in the organic synaptic devices. This study represents an important step toward
building future artificial neuromorphic systems with newly emerged ion gel gated
organic synaptic devices.
PMID- 27608137
TI - Cobalt(III)-Catalyzed Intramolecular Cross-Dehydrogenative C-H/X-H Coupling:
Efficient Synthesis of Indoles and Benzofurans.
AB - An efficient cobalt(III)-catalyzed intramolecular cross-dehydrogenative C-H/N-H
coupling of ortho-alkenylanilines has been developed utilizing O2 as a terminal
oxidant. The developed reaction tolerates various reactive functional groups and
allows the synthesis of diverse indole derivatives in good to excellent yields.
The method was successfully extended to the synthesis of benzofurans through the
intramolecular cross-dehydrogenative C-H/O-H coupling of ortho-alkenylphenols.
PMID- 27608138
TI - Hierarchical Self-Assembly of Responsive Organoplatinum(II) Metallacycle-TMV
Complexes with Turn-On Fluorescence.
AB - Here we report that the rod-like tobacco mosaic virus (TMV), having a negatively
charged surface, can be assembled into three-dimensional micrometer-sized bundle
like superstructures via multiple electrostatic interactions with a positively
charged molecular "glue", namely, a tetraphenylethylene (TPE)-based discrete
organoplatinum(II) metallacycle (TPE-Pt-MC). Due to the nanoconfinement effect in
the resultant TMV/TPE-Pt-MC complexes and the aggregation-induced emission (AIE)
activity of the TPE units, these hierarchical architectures result in a dramatic
fluorescence enhancement that not only provides evidence for the formation of
novel metal-organic biohybrid materials but also represents an alternative to
turn-on fluorescence. Moreover, the dissociation of these final constructs and
subsequent release of individual virus have been achieved by disrupting the TPE
Pt-MC core using tetrabutylammonium bromide (TBAB). This strategy is also
compatible with other protein-based nanoparticles such as bacteriophage M13 and
ferritin, proving the generality of this approach. Hence, this research will open
new routes for the fabrication of functional biohybrid materials involving metal
organic complexes and anisotropically shaped bionanoparticles.
PMID- 27608139
TI - Live Cell Imaging: Assessing the Phototoxicity of 488 and 546 nm Light and
Methods to Alleviate it.
AB - In live cell imaging of fluorescent proteins, phototoxicity of the excitation
light can be problematical. Cell death is obvious, but reduced cell viability can
make the interpretation of observations error prone. We characterized the
phototoxic consequences of 488 and 546 nm light on untransformed human cells and
tested methods that have or could be used to alleviate photodamage. Unlabeled
RPE1 cells were given single 0.5-2.5 min irradiations in early G1 from a mercury
arc lamp on a fluorescence microscope. Four hundred eighty-eight nanometer light
produced a dose-dependent decrease in the percentage of cells that progressed to
mitosis, slowing of the cell cycle for some of those entering mitosis, and a ~12%
incidence of cell death for the highest dose. For 546 nm light we found a 10-15%
reduction in the percentage of cells entering mitosis, no strong dose dependency,
and a ~2% incidence of cell death for the longest irradiations. For cells
expressing GFP-centrin1 or mCherry-centrin1, fewer entered mitosis for each dose
than unlabeled cells. For constant total dose 488 nm light irradiations of
unlabeled cells, reducing the intensity 10-fold or spreading the exposures out as
a series of 10 sec pulses at 1 min intervals produced a minor and not consistent
improvement in the percentage of cells entering mitosis. Reducing oxidative
processes, by culturing at ~3% oxygen or adding the reducing agent Trolox
noticeably increased the fraction of cells entering mitosis. Thus, for long-term
imaging there can be value to using RFP constructs and for GFP-tagged proteins
reducing oxidative processes. J. Cell. Physiol. 232: 2461-2468, 2017. (c) 2016
Wiley Periodicals, Inc.
PMID- 27608140
TI - Clustering-Triggered Emission of Nonconjugated Polyacrylonitrile.
AB - Intrinsic emission from nonconjugated polymers has attracted considerable
attention owing to its fundamental importance and intensive applications in
diverse fields. The emission mechanism, however, is still in debate. Herein,
nonconjugated polyacrylonitrile (PAN) molecules are found to be virtually
nonluminescent in dilute solutions, while being highly emissive when concentrated
or aggregated as nanosuspensions, solid powders, and films, exhibiting distinct
aggregation-induced emission (AIE) characteristics. Moreover, triplet emissions
of delayed fluorescence and room temperature phosphorescence are detected from
the solid powders. Such unique emission of nonconjugated PAN is ascribed to the
formation of cyano clusters, which act as the exact chromophores. In these
clusters, through space electronic interactions, namely overlap of pi and lone
pair (n) electrons among cyano groups extend the conjugation and meanwhile
rigidify the molecular conformations, thus offering remarkable emission upon
irradiation. The AIE phenomenon can also be well rationalized by the formation of
cyano clusters together with conformation rigidification. And the triplet
emissions shall be originated from the n-pi* transition owing to the presence of
lone pairs. It is believed that such clustering-triggered emission mechanism is
instructive for further development of unorthodox luminogens.
PMID- 27608141
TI - Programmable Wrinkling of Self-Assembled Nanoparticle Films on Shape Memory
Polymers.
AB - Hierarchically structured materials, inspired by sophisticated structures found
in nature, are finding increasing applications in a variety of fields. Here, we
describe the fabrication of wrinkled gold nanoparticle films, which leverage the
structural tunability of gold nanoparticles to program the wavelength and
amplitude of gold wrinkles. We have carefully examined the structural evolution
and tuning of these wrinkled surfaces through varying nanoparticle parameters
(diameter, number of layers, density) and substrate parameters (number of axes
constrained during wrinkling) through scanning electron microscopy and cross
sectional transmission electron microscopy. It is found that nanoparticle layers
of sufficient density are required to obtain periodical wrinkled structures. It
was also found that tuning the nanoparticle diameter and number of layers can be
used to program the wrinkle wavelength and amplitude by changing the film
thickness and mechanical properties. This dual degree of tunability, not
previously seen with continuous films, allows us to develop one of the smallest
wrinkles developed to date with tunability in the sub-100 nm regime. The effect
of the induced structural tunability on the enhancement of the intensity of the 4
mercaptopyridine Raman spectra is also studied through the application of these
devices as substrates for surface-enhanced Raman spectroscopy (SERS), where
wrinkling proves to be an effective method for enhancing the SERS signal in cases
where there is an inherently low density of gold nanoparticles.
PMID- 27608142
TI - Measured acoustic intensities for clinical diagnostic ultrasound transducers and
correlation with thermal index.
AB - OBJECTIVES: To investigate if the thermal index for bone (TIB) displayed on
screen is an adequate predictor for the derated spatial-peak temporal-average
(ISPTA.3 ) and spatial-peak pulse-average (ISPPA.3 ) acoustic intensities in a
selection of clinical diagnostic ultrasound machines and transducers. METHODS: We
calibrated five clinical diagnostic ultrasound scanners and 10 transducers, using
two-dimensional grayscale, color Doppler and pulsed-wave Doppler, both close to
and far from the transducer, with a TIB between 0.1 and 4.0, recording 103 unique
measurements. Acoustic measurements were performed in a bespoke three-axis
computer-controlled scanning tank, using a 200-MUm-diameter calibrated needle
hydrophone. RESULTS: There was significant but poor correlation between the
acoustic intensities and the on-screen TIB. At a TIB of 0.1, the ISPTA.3 range
was 0.51-50.49 mW/cm2 and the ISPPA.3 range was 0.01-207.29 W/cm2 . At a TIB of
1.1, the ISPTA.3 range was 19.02-309.44 mW/cm2 and the ISPPA.3 range was 3.87
51.89 W/cm2 . CONCLUSIONS: TIB is a poor predictor for ISPTA.3 and ISPPA.3 and
for the potential bioeffects of clinical diagnostic ultrasound scanners.
Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27608143
TI - Anatomical, functional and quality-of-life results for mastoid and epitympanic
obliteration with bioactive glass s53p4: a prospective clinical study.
AB - OBJECTIVE: To analyse the anatomical, functional and quality-of-life results when
using bioactive glass in mastoid and epitympanic obliteration. DESIGN:
Prospective clinical study. SETTING: Tertiary referral centre. PARTICIPANTS:
Forty-one cases (39 patients) operated between May 2013 and January 2015. MAIN
OUTCOME MEASURES: Anatomical results were evaluated by otomicroscopy 1 year after
surgery and using imaging to detect residual disease. Functional results were
studied by postoperative hearing gain. Quality of life was assessed with the
Glasgow Benefit Inventory questionnaire and the success of surgery by a surgery
specific questionnaire. RESULTS: At 1 year, all patients presented a well-healed
external auditory canal, with an intact tympanic membrane. In cases with
cholesteatoma (n = 23), no recurrent retraction pockets or residual disease were
observed on imaging studies. The overall air-bone gap closure was 7.7 +/- 1.84 dB
(mean +/- se of the mean, P < 0.001, paired t-test). No significant differences
were found on hearing results when comparing primary versus revision surgery,
canal-wall-up versus canal-wall-down obliterations, type of tympanoplasty and
presence of cholesteatoma (multifactor anova). The Glasgow Benefit Inventory
improved with an average score of 28 and the success of surgery questionnaire
showed a significant improvement in ear discharge and a moderate improvement in
hearing and equilibrium. CONCLUSIONS: The use of bioactive glass for mastoid and
epitympanic obliteration in canal-wall-down or canal-wall-up tympanoplasties is
an effective procedure in both primary and revision surgery. The anatomical and
functional results appear to be well correlated with patient experience and to
the improvement in quality of life.
PMID- 27608144
TI - Finding a Focus for Nursing: The Caring Concept.
AB - Many nursing theorists claim caring as the aspect of nursing that differentiates
it from other health care professions. Newman et al defined the focus of nursing
as "the study of caring in the human health experience," yet there is little
consensus among nurses about the validity of this statement. The purpose of this
article is to explore the concept of caring as it has been defined by various
nursing scholars and to determine whether the focus of nursing knowledge
development can appropriately be defined as "the study of caring in the human
health experience."
PMID- 27608146
TI - Death Is a Social Justice Issue: Perspectives on Equity-Informed Palliative Care.
AB - All too often, palliative care services are not responsive to the needs of those
who are doubly vulnerable, being that they are both in need of palliative care
services and experiencing deficits in the social determinants of health that
result in complex, intersecting health and social concerns. In this article, we
argue for a reorientation of palliative care to explicitly integrate the premises
of health equity. We articulate the philosophical, theoretical, and empirical
scaffolding required for equity-informed palliative care and draw on a current
study to illustrate such an approach to the care of people who experience
structural vulnerabilities.
PMID- 27608145
TI - Exploring Preterm Mothers' Personal Narratives: Influences and Meanings.
AB - In this article we report on a study exploring personal narratives of mothers of
former preterm infants and the attributed meaning related to that experience over
time. Using narrative inquiry as the research method, in-depth, unstructured
interviews were conducted with 6 preterm mothers. Findings reveal that a preterm
mother's experience is informed by contextual, intrapersonal, and interpersonal
dynamics, some predating the birth often with effects that continue for years
beyond it. By learning a preterm mother's unique experience and its attributed
meaning, nurses can better understand the resulting effect on maternal/family
health and well-being and tailor nursing interventions accordingly.
PMID- 27608147
TI - Exercising Nursing Essential and Effective Freedom in Behalf of Social Justice: A
Humanizing Model.
AB - This article expands upon previous work by the authors to develop a model of
nursing essential and effective freedom to facilitate nursing action in behalf of
social justice. The article proposes that while social justice is rooted in
nursing's ontological, epistemological, and moral foundations, the discipline's
social justice mandate is constrained by its historical and contemporary location
within an institutionalized medical paradigm. We present a model of nursing
"essential" and "effective" freedom based on the philosophy of Bernard Lonergan
to illustrate how nursing can transcend these barriers. This humanizing model is
illustrated through personal narratives of the authors.
PMID- 27608148
TI - Quality Indicators and Parental Satisfaction With Perinatal Palliative Care in
the Intrapartum Setting After Diagnosis of a Life-Limiting Fetal Condition.
AB - Measurement of quality indicators (QIs) in perinatal palliative care has not been
addressed. Parents who chose to continue pregnancy after a diagnosis of a life
limiting fetal condition described perceptions of quality care and their
satisfaction with care. This research identified which QIs explained parental
satisfaction. High QI scores are associated with parental satisfaction. Parents
who were satisfied reported 2.9 times the odds that their baby was treated with
dignity and respect and 3.4 times the odds their medical care was addressed. This
research is a first step in developing a robust measure of QIs in perinatal
palliative care.
PMID- 27608149
TI - Is Obesity Associated With Adverse Workers' Compensation Claims Outcomes?
AB - BACKGROUND: A pilot study indicated that obesity was associated with an increased
time lost from work and higher costs among workers' compensation claimants
sustaining severe, but not minor injuries. OBJECTIVE: The aim of this study was
to further test the hypotheses by increasing sample size and controlling for
additional confounding factors. METHOD: Cost and lost time outcomes were assessed
for 2301 lost time workers' compensation claims filed in 2011 and 2012 followed
to the end of the first quarter of the third postinjury year. RESULT: Adjusting
for gender, age, marital status, attorney involvement, and spinal procedures, the
odds ratios of incurring a claim expense at least $100,000 after a severe injury
for an overweight or obese versus normal weight claimant was 2.11 [95% confidence
interval (95% CI): 1.04 to 4.29] and 2.23 (95% CI:1.12-4.46), respectively.
CONCLUSION: Obesity was associated with increased costs among workers'
compensation claimants sustaining severe, but not minor injuries.
PMID- 27608150
TI - The Impact of Contract Operations on Safety in Underground Coal Mines.
AB - OBJECTIVE: The aim of this study was to test for differences in injury rates for
contractor-operated underground coal mines relative to owner-operated mines in
Kentucky, controlling for other covariates. METHODS: We used disparities between
MSHA contractor data and surface reclamation permit data to identify mines
operated by contractors. We then used negative binomial regression to estimate
injury rates from 1999 to 2013, controlling for mine and controller
characteristics available from MSHA and the Energy Information Administration
(EIA). RESULTS: Contractor-operated mines with 15 or fewer full-time equivalent
workers (FTEs) had a statistically significant 57% higher covariate-adjusted
reported traumatic injury rate than similar mines without contract operators.
Larger contractor-operated mines did not have a statistically significant
elevated rate. CONCLUSIONS: We detected a significant elevation of traumatic
injury rates only among the smallest contractor-operated mines. This increase
appears substantial enough to warrant attention.
PMID- 27608153
TI - A Seven-Year Longitudinal Claim Analysis to Assess the Factors Contributing to
the Increased Severity of Work-Related Injuries.
AB - BACKGROUND: In recent decades, the frequency of Medical Only (MO) and Lost Time
(LT) workers' compensation claims has decreased, while average severity (medical
and indemnity costs) has increased. OBJECTIVE: The aim of this study was to
compare claim frequency, mix, and severity (cost) over two periods using a claim
cohort follow-up method. METHODS: Sixty-two thousand five hundred thirty-three
claims during two periods (1999 to 2002 and 2003 to 2006) were followed seven
years postinjury. Descriptive analysis and significant testing methods were used
to compare claim frequency and costs. RESULTS: The number of claims per $1 M of
premium decreased 50.4% for MO claims and 35.6% for LT claims, consequently
increasing the LT claim proportion. The average cost of LT claims did not
increase. CONCLUSION: The severity increase is attributable to the proportional
change in LT and MO claims. While the number of LT claims decreased, the
inflation-adjusted average cost of LT claims did not increase.
PMID- 27608154
TI - Yo-Yo Diving and Risk of Decompression Sickness in Trainee Military Divers.
PMID- 27608155
TI - Conflicts of Interest and Publication Bias.
PMID- 27608156
TI - Response to Comments by Ryan et al.
PMID- 27608157
TI - Cost-utility analysis of sofosbuvir for the treatment of genotype 2 chronic
hepatitis C in Japan.
AB - OBJECTIVE: Across Japan, around 2 million people are infected with hepatitis C
virus (HCV) with long-term complications such as cirrhosis, hepatocellular
carcinoma (HCC) and liver transplant (LT). Current treatment options have several
limitations due to side effects, interferon intolerability and ineligibility,
long treatment durations and low sustained virological responses (SVR) rates,
especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide
analog NS5B polymerase inhibitor with pan-genotypic activity. SOF, administered
in combination with ribavirin (RBV) with or without pegylated interferon (PEGIFN)
resulted in high SVR rates across genotype (GT) 1-6 patients. It is also the
first available regimen for patients that are unsuitable for interferon. This
analysis assessed the cost-utility ratio of sofosbuvir in GT2 patients in Japan.
RESEARCH DESIGN AND METHODS: A Markov model followed a cohort of 10,000 GT2
patients until patients reached 100 years of age. Approximately 20% of patients
initiated treatment at the cirrhotic stage. Comparators were based on the current
recommendations in Japan, including PEGIFN with ribavirin (RBV), telaprevir (TVR)
in combination with PEGIFN + RBV and no treatment. Costs and outcomes were
discounted at 2%. RESULTS: Sofosbuvir was cost-effective across all the studied
indications, especially in patients unsuitable for interferon, with incremental
cost-effectiveness ratios (ICERs) lower than JPY 5,000,000. Compared to the other
treatments included in the analysis, SOF + RBV resulted in improved clinical
outcomes. Results were robust to sensitivity analyses. CONCLUSION: SOF combined
with RBV was shown to be cost-effective in GT2 patients in Japan. Compared to
PEGIFN + RBV, TVR + PEGIFN + RBV and no treatment SOF offers a more efficacious,
shorter and better tolerated treatment option and extends treatment to reach HCV
infected patients who are ineligible for interferon-based regimens. Although
adverse events were not included in the analyses, this would not make any changes
to our conclusion.
PMID- 27608158
TI - Re: "Comparison of Fasanella-Servat and Small-Incision Techniques for
Involutional Ptosis Repair".
PMID- 27608159
TI - Reply Re: "Comparison of Fasanella-Servat and Small-Incision Techniques for
Involutional Ptosis Repair".
PMID- 27608160
TI - Re: "Beauty Is in the Eye of the Beholder: Body Dysmorphic Disorder in Ophthalmic
Plastic and Reconstructive Surgery".
PMID- 27608161
TI - Reply re: "Beauty Is in the Eye of the Beholder: Body Dysmorphic Disorder in
Ophthalmic Plastic and Reconstructive Surgery".
PMID- 27608162
TI - Image Guidance for Orbital Surgery.
PMID- 27608164
TI - Preeclampsia: Vascular Pathophysiological Mechanism and the Basis for Early
Diagnosis and Treatment.
PMID- 27608163
TI - Active saponins from root of Pueraria peduncularis (Grah. ex Benth.) Benth. and
their molluscicidal effects on Pomacea canaliculata.
AB - BACKGROUND: Pueraria peduncularis (Grah. ex Benth.) Benth., which belongs to the
Leguminosae family, exhibits resistance to many crop pests in agricultural
production. Pomacea canaliculata is an important invasive snail in rice fields
and causes severe yield losses. To evaluate the toxicity of P. peduncularis to P.
canaliculata, in this study the molluscicidal activity of root extracts of P.
peduncularis was tested against P. canaliculata; the active compounds were
isolated, and the structures of these compounds were analysed using nuclear
magnetic resonance (NMR) analysis and mass spectral analysis. RESULTS: Our
results showed that the molluscicidal activity of the root crude extract differed
between P. canaliculata with different shell diameters after treatment for 72 h.
The median lethal concentration (LC50 ) was 5.511 mg L-1 against snails of 1.5 +/
0.2 cm diameter and 12.383 mg L-1 against snails of 2.5 +/- 0.2 cm diameter.
Furthermore, two active ingredients isolated from root methanol extracts were
identified as pedunsaponin A and pedunsaponin C. Both pedunsaponin A and
pedunsaponin C showed strong molluscicidal activities, with LC50 values of 3.893
and 4.252 mg L-1 , respectively, against snails with shell diameters of 1.5 +/-
0.2 cm after treatment for 72 h. CONCLUSION: Pueraria peduncularis extracts
exhibit high molluscicidal activity and have great potential value for exploring
a molluscicide to control Pomacea canaliculata. (c) 2016 Society of Chemical
Industry.
PMID- 27608165
TI - HIV Prevalence among Pregnant Women in Brazil: A National Survey.
AB - Background This study was conducted to determine the seroprevalence of HIV among
pregnant women in Brazil and to describe HIV testing coverage and the uptake of
antenatal care (ANC). Methods Between October 2010 and January 2012, a
probability sample survey of parturient women aged 15-49 years who visited public
hospital delivery services in Brazil was conducted. Data were collected from
prenatal reports and hospital records. Dried blood spot (DNS) samples were
collected and tested for HIV. We describe the age-specific prevalence of HIV
infection and ANC uptake with respect to sociodemographic factors. Results Of the
36,713 included women, 35,444 (96.6%) were tested for HIV during delivery
admission. The overall HIV prevalence was of 0.38% (95% confidence interval [CI]:
0.31-0.48), and it was highest in: the 30 to 39 year-old age group (0.60% [0.40
0.88]), in the Southern region of Brazil (0.79% [0.59-1.04]), among women who had
not completed primary (0.63% [0.30-1.31]) or secondary (0.67% [0.49-0.97]) school
education, and among women who self-reported as Asian (0.94% [0.28-3.10]). The
HIV testing coverage during prenatal care was of 86.6% for one test and of 38.2%
for two tests. Overall, 98.5% of women attended at least 1 ANC visit, 90.4%
attended at least 4 visits, 71% attended at least 6 visits, and 51.7% received
ANC during the 1st trimester. HIV testing coverage and ANC uptake indicators
increased with increasing age and education level of education, and were highest
in the Southern region. Conclusions Brazil presents an HIV prevalence of less
than 1% and almost universal coverage of ANC. However, gaps in HIV testing and
ANC during the first trimester challenge the prevention of the vertical
transmission of HIV. More efforts are needed to address regional and social
disparities.
PMID- 27608166
TI - Lymphatic Transport and Lymphocyte Targeting of a Triglyceride Mimetic Prodrug Is
Enhanced in a Large Animal Model: Studies in Greyhound Dogs.
AB - In previous studies, a triglyceride (TG) mimetic prodrug of the model
immunomodulator mycophenolic acid (MPA) was shown to significantly enhance
lymphatic transport of MPA-related species in the rat. The rat gastrointestinal
tract, however, is somewhat different from that in higher order species such as
dogs and humans and may underestimate lymphatic transport. Here the effectiveness
of the prodrug strategy has been examined in conscious greyhound dogs, the GI
physiology of which is more representative of that in humans. The bioavailability
and lymphatic transport of free MPA and total MPA related materials were examined
following oral administration of the parent drug (MPA) and the prodrug (2-MPA-TG)
to both thoracic lymph duct cannulated and intact (noncannulated) greyhound dogs.
The enrichment of free MPA in lymph nodes and lymph-derived lymphocytes was also
determined to examine the efficiency of drug targeting to potential sites of
action within the lymph. Via biochemical integration into a series of site
specific metabolic processes, the prodrug markedly increased (288-fold) lymphatic
transport of total MPA related material (present as re-esterified 2-MPA-TG) when
compared to the parent MPA and the extent of lymphatic transport was
significantly greater in the dog (36.4% of the dose recovered in lymph) when
compared to the previous data in the rat (13.4% of the dose). Conversion from 2
MPA-TG derivatives to parent MPA occurred in vivo, resulting in a marked increase
in MPA concentrations in lymph nodes (5-6-fold) and lymph lymphocytes (21-fold),
when compared to animals administered the parent drug. In conclusion, the data
demonstrate that the TG prodrug of MPA facilitates efficient delivery of MPA to
the lymphatic system in dogs and suggest that the TG prodrug strategy may more
effectively facilitate targeted delivery in large animals than in rats.
PMID- 27608167
TI - Does the Harvesting Technique Affect the Properties of Adipose-Derived Stem
Cells?-The Comparative Biological Characterization.
AB - The objective of this study was to evaluate complex biological properties of
human stem cells isolated from adipose tissue (ASCs) harvested utilizing
different methods: surgical resection (R), power-assisted liposuction (PAL), and
laser-assisted liposuction (LAL). ASCs were isolated from healthy donors, due to
surgical resection, power-, and laser-assisted liposuction. Isolated cells were
characterized by their clonogenicity, proliferation rate, doubling time,
multilineage differentiation, and senescence potential. The average number of
ASCs from 1g/1 ml of solid adipose tissue/lipoaspirate was 2.9 * 105 +/- 2.4 *
105 , 1.1 * 105 +/- 0.8 * 105 , and 1.2 * 105 +/- 0.7 * 105 , respectively, for
ASCsR, ASCsPAL, and ASCsLAL. However, number of colonies formed by ASCsR and
ASCsPAL was significantly higher compared to the average number of colonies
formed by ASCsLAL. Also, in comparison to other analyzed cell groups, ASCsPAL
obtained the highest proliferative activity. All analyzed cells were
characterized by stable expression of CD90 and CD44 markers during prolonged
culture. Expression of CD34 and CD45 markers was decreasing in subsequent
passages. Presented study shows that different ASCs collection method affects
some basic characteristics of these cells, such as number of isolated cells,
clonogeneity, or doubling time. J. Cell. Biochem. 118: 1097-1107, 2017. (c) 2016
Wiley Periodicals, Inc.
PMID- 27608168
TI - Low levels of calcium or vitamin D - which is more important in systemic lupus
erythematosus patients? An extensive data analysis.
AB - OBJECTIVES: Several reports have indicated an association between systemic lupus
erythematosus (SLE) and low levels of vitamin D. We examined several blood work
parameters in SLE patients and controls and performed an extensive data analysis
in order to investigate the links between blood levels of calcium, vitamin D, and
SLE disease. METHODS: 4,278 SLE patients and 16,443 age and sex-matched controls
were selected from a national health insurer database in Israel. Patients with no
blood work results or having renal disease were excluded. Retrospective data from
five consecutive years of routine blood work results were then analysed for mean
serum calcium, albumin, albumin-corrected calcium, vitamin D levels, and the
presence of a hypocalcaemic episode (Corrected Ca <8.5 mg/dL). RESULTS: The mean
levels of corrected serum calcium levels were slightly higher among SLE patients
than controls (9.23+/-0.34 vs. 9.19+/-0.36 mg/dL p<=.001 respectively). In
contrast to results of published studies, SLE patients had slightly higher levels
of 25(OH)-vitamin D (SLE patients: 22.2+/-9.06 ng/ml, controls: 20.0+/-8.76
ng/ml, p<=.001). The most impressive finding entailing SLE patients was that they
were twice as likely to experience episodes of hypocalcaemia in comparison to
controls (SLE patients: 13.8%, controls: 6.4%, OR 2.34; 95% CI 2.33-2.83).
CONCLUSIONS: Calcium levels may play a significant role in the SLE disease
process, more than originally thought, since SLE patients are at a higher risk
for hypocalcaemic events. Specific changes in vitamin D and calcium homeostasis
in SLE patients may be responsible for the severity of symptoms. Further research
is required to determine the role of calcium supplementation.
PMID- 27608169
TI - Raccoon Roundworm Infection Associated with Central Nervous System Disease and
Ocular Disease - Six States, 2013-2015.
AB - Baylisascaris procyonis, predominantly found in raccoons, is a ubiquitous
roundworm found throughout North America. Although raccoons are typically
asymptomatic when infected with the parasite, the larval form of Baylisascaris
procyonis can result in fatal human disease or severe neurologic outcomes if not
treated rapidly. In the United States, Baylisascaris procyonis is more commonly
enzootic in raccoons in the midwestern and northeastern regions and along the
West Coast (1). However, since 2002, infections have been documented in other
states (Florida and Georgia) and regions (2). Baylisascariasis is not a
nationally notifiable disease in the United States, and little is known about how
commonly it occurs or the range of clinical disease in humans. Case reports of
seven human baylisascariasis cases in the United States diagnosed by
Baylisascaris procyonis immunoblot testing at CDC are described, including review
of clinical history and laboratory data. Although all seven patients survived,
approximately half were left with severe neurologic deficits. Prevention through
close monitoring of children at play, frequent handwashing, and clearing of
raccoon latrines (communal sites where raccoons defecate) are critical
interventions in curbing Baylisascaris infections. Early treatment of suspected
cases is critical to prevent permanent sequelae.
PMID- 27608170
TI - Stage-specific roles of FGF2 signaling in human neural development.
AB - This study elucidated the stage-specific roles of FGF2 signaling during neural
development using in-vitro human embryonic stem cell-based developmental
modeling. We found that the dysregulation of FGF2 signaling prior to the onset of
neural induction resulted in the malformation of neural rosettes (a neural tube
like structure), despite cells having undergone neural induction. The aberrant
neural rosette formation may be attributed to the misplacement of ZO-1, which is
a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the
apical region of neural rosettes, subsequently led to abnormal neurogenesis.
Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a
reduction in cell proliferation, an increase in numbers of cells with cell-cycle
exit, and premature neurogenesis. These effects may be mediated by NUMB, to which
expression was observed enriched in the apical region of neural rosettes after
FGF2 signaling inhibition coinciding with the disappearance of PAX6+/Ki67+ neural
stem cells and the emergence of MAP2+ neurons. Moreover, our results suggested
that the hESC-based developmental system reserved a similar neural stem cell
niche in vivo.
PMID- 27608172
TI - Epidemiology matters: peering inside the "black box" in economic evaluations of
genetic testing.
PMID- 27608171
TI - arrEYE: a customized platform for high-resolution copy number analysis of coding
and noncoding regions of known and candidate retinal dystrophy genes and retinal
noncoding RNAs.
AB - PURPOSE: Our goal was to design a customized microarray, arrEYE, for high
resolution copy number variant (CNV) analysis of known and candidate genes for
inherited retinal dystrophy (iRD) and retina-expressed noncoding RNAs (ncRNAs).
METHODS: arrEYE contains probes for the full genomic region of 106 known iRD
genes, including those implicated in retinitis pigmentosa (RP) (the most frequent
iRD), cone-rod dystrophies, macular dystrophies, and an additional 60 candidate
iRD genes and 196 ncRNAs. Eight CNVs in iRD genes identified by other techniques
were used as positive controls. The test cohort consisted of 57 patients with
autosomal dominant, X-linked, or simplex RP. RESULTS: In an RP patient, a novel
heterozygous deletion of exons 7 and 8 of the HGSNAT gene was identified: c.634
408_820+338delinsAGAATATG, p.(Glu212Glyfs*2). A known variant was found on the
second allele: c.1843G>A, p.(Ala615Thr). Furthermore, we expanded the allelic
spectrum of USH2A and RCBTB1 with novel CNVs. CONCLUSION: The arrEYE platform
revealed subtle single-exon to larger CNVs in iRD genes that could be
characterized at the nucleotide level, facilitated by the high resolution of the
platform. We report the first CNV in HGSNAT that, combined with another mutation,
leads to RP, further supporting its recently identified role in nonsyndromic
iRD.Genet Med 19 4, 457-466.
PMID- 27608174
TI - Estimation of the number of people with Down syndrome in the United States.
AB - PURPOSE: An accurate accounting of persons with Down syndrome (DS) has remained
elusive because no population-based registries exist in the United States. The
purpose of this study was to estimate this population size by age, race, and
ethnicity. METHODS: We predicted the number of people with DS in different age
groups for different calendar years using estimations of the number of live
births of children with DS from 1900 onward and constructing DS-specific
mortality rates from previous studies. RESULTS: We estimate that the number of
people with DS living in the United States has grown from 49,923 in 1950 to
206,366 in 2010, which includes 138,019 non-Hispanic whites, 27,141 non-Hispanic
blacks, 32,933 Hispanics, 6,747 Asians/Pacific Islanders, and 1,527 American
Indians/American Natives. Population prevalence of DS in the United States, as of
2010, was estimated at 6.7 per 10,000 inhabitants (or 1 in 1,499). CONCLUSION:
Until 2008, DS was a rare disease. In more recent decades, the population growth
of people with DS has leveled off for non-Hispanic whites as a consequence of
elective terminations. Changes in childhood survival have impacted the age
distribution of people with DS, with more people in their fourth, fifth, and
sixth decades of life.Genet Med 19 4, 439-447.
PMID- 27608173
TI - A secondary benefit: the reproductive impact of carrier results from newborn
screening for cystic fibrosis.
AB - PURPOSE: Newborn screening (NBS) for cystic fibrosis (CF) can identify carriers,
which is considered a benefit that enables reproductive planning. We examined the
reproductive impact of carrier result disclosure of NBS for CF. METHODS: We
surveyed mothers of carrier infants after NBS (Time 1) and 1 year later (Time 2)
to ascertain intended and reported communication of their infants' carrier
results to relatives, carrier testing for themselves/other children, and
reproductive decisions. A sub-sample of mothers was also interviewed at Time 1
and Time 2. RESULTS: The response rate was 54%. A little more than half (55%) of
mothers underwent carrier testing at Time 1; another 40% of those who intended to
undergo testing at Time 1 underwent testing at Time 2. Carrier result
communication to relatives was high (92%), but a majority of participants did not
expect the results to influence family planning (65%). All interviewed mothers
valued learning their infants' carrier results. Some underwent carrier testing
and then shared results with family. Others did not use the results or used them
in unintended ways. CONCLUSION: Although mothers valued learning carrier results
from NBS, they reported moderate uptake of carrier testing and limited influence
on family planning. Our study highlights the secondary nature of the benefit of
disclosing carrier results of NBS.Genet Med 19 4, 403-411.
PMID- 27608175
TI - Switch to agalsidase alfa after shortage of agalsidase beta in Fabry disease: a
systematic review and meta-analysis of the literature.
AB - BACKGROUND: In 2009, the agalsidase beta shortage resulted in switching to
agalsidase alfa treatment for many Fabry disease patients, offering the unique
opportunity to compare the effects of the two drugs. Because single studies
describing effects of switching on the disease course are limited and
inconclusive, we performed a systematic review and meta-analysis of existing
data. METHODS: Relevant studies were identified in the PubMed, Cochrane, ISI Web,
and SCOPUS databases from July 2009 to September 2015. The following parameters
were analyzed: clinical events, changes in organ function or structure, disease
related symptoms, lyso-Gb3 plasma levels, and adverse effects. CONCLUSIONS: The
nine studies (217 patients) included in our systematic review showed only
marginal differences in most of the evaluated parameters. Seven of these studies
were included in the meta-analysis (176 patients). The pooled incidence rate of
major adverse events was reported for five studies (150 patients) and was equal
to 0.04 events per person-year. No significant change was observed after the
shift in glomerular filtration rate, whereas left ventricular mass index, left
ventricular posterior wall dimension, and ejection fraction were significantly
reduced over time. Our data showed that the switch to agalsidase alfa was well
tolerated and associated with stable clinical conditions.Genet Med 19 3, 275-282.
PMID- 27608176
TI - National survey: Evaluation of cardiovascular risk factors in Thai patients with
type 2 diabetes and chronic kidney disease after the development of
cardiovascular disease.
AB - AIM: The aim of the present study was to evaluate the achievement in controlling
the risk factors of cardiovascular diseases (CVD) in Thai patients with type 2
diabetes (T2DM) and chronic kidney disease (CKD). METHODS: The DMHT dataset from
2011 to 2012, which was the cross-sectional study of the national survey in Thai
patients with T2DM was analyzed. RESULTS: There were 1254 of 15 149 diabetic
patients with estimated glomerular filtration rate (eGFR) less than 60 mL/min per
1.73 m2 that had developed CVD for more than 12 months. The prevalence of CVD was
8.3%. The mean age in years was 68.2 with a standard deviation (SD) of 8.7. Males
and females were 38.7 and 61.3%, respectively. The mean duration of diabetes was
8.5 (SD 0.2) years. The mean body mass index was 25.5 (SD 4.4) kg/m2 . The
percentage of patients with the target level of blood pressure control at
<=130/80 mm Hg was 47.1%. The percentage of patients who received angiotensin
converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) was
58.9%. The percentage of patients with the target level of LDL control at <70
mg/dL was 17.2%. The percentage of patients with the target level of HbA1C at 7%
was 39.2%. There were 63 (5.0%) patients having recurrent CVD. CONCLUSIONS: Most
Thai patients with T2DM and CKD with eGFR < 60 mL/min per 1.73 m2 could not
achieve the therapeutic goals after the development of CVD. The national health
policy should be planned to improve the quality of care to increase the number of
patients who achieve the recommended goals.
PMID- 27608178
TI - Phosphorus and Halogen Co-Doped Graphene Materials and their Electrochemistry.
AB - Doping of graphene materials with heteroatoms is important as it can change their
electronic and electrochemical properties. Here, graphene is co-doped with n-type
dopants such as phosphorus and halogen (Cl, Br, I). Phosphorus and halogen are
introduced through the treatment of graphene oxide with PX3 gas (PCl3 , PBr3 ,
and PI3 ). Graphene oxides are prepared through chlorate and permanganate routes.
Detailed chemical and structural characterization demonstrates that the graphene
sheets are covered homogeneously by phosphorus and halogen atoms. It is found
that the amount of phosphorus and halogen introduced depends on the graphene
oxide preparation method. The electrocatalytic effect of the resulting co-doped
materials is demonstrated for industrially relevant electrochemical reactions
such as the hydrogen evolution and oxygen reduction reactions.
PMID- 27608177
TI - Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor
Antagonist.
AB - We developed a compound library for orally available gonadotropin-releasing
hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the
basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496)
for further in vivo studies. Compound 18a exhibited more selective antagonistic
activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and
this compound also showed inhibitory effects on GnRH-mediated signaling pathways.
Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved
bioavailability and superior gonadotropic suppression activity compared with
Elagolix, the most clinically advanced compound. Considering that 18a exhibited
highly potent and selective antagonistic activity toward the hGnRHRs along with
favorable pharmacokinetic profiles, we believe that 18a may represent a promising
candidate for an orally available hormonal therapy.
PMID- 27608179
TI - Clinical impact of induction treatment modalities and optimal timing of
radiotherapy for the treatment of limited-stage NK/T cell lymphoma.
AB - This study retrospectively investigated the optimal timing of radiotherapy (RT)
in patients with limited-stage extranodal NK/T-cell lymphoma (ENTKL). Among 158
patients with newly diagnosed stage I/II ENKTL, 61 patients were treated with
sequential chemotherapy followed by radiotherapy (SCRT), 55 with concurrent
chemoradiotherapy followed by non-anthracycline-based chemotherapy (CCRT/CT), and
42 with chemotherapy (CT) only. The 5-year overall survival (OS) rate did not
differ between SCRT (77.7+/-5.5%) and CCRT/CT (68.9+/-6.8%; p=0.234). In the SCRT
group, 18 patients (29.5%) relapsed within the RT field and 6 (9.8%) at systemic
sites, while in the CCRT/CT group, 9 patients (16.4%) relapsed at the primary
site and 14 (25.5%) at systemic sites. The 5-year cumulative incidence of relapse
(CIR) at primary sites was 26.3% and 19.2% after SCRT and CCRT/CT (p=0.308),
while the 5-year CIR of systemic sites was 8.7% and 26.5% after SCRT and CCRT/CT,
respectively (p=0.010). In the multivariate analysis, NK/T-cell Prognostic Index
score and CR achievement were the most important prognostic factors for survival.
Although up-front RT had limitations in systemic disease control and was
associated with an increased risk of systemic relapse during RT compared to SCRT,
timing of RT did not significantly affect survival outcomes.
PMID- 27608180
TI - A Bayesian Network-Based Approach to Selection of Intervention Points in the
Mitogen-Activated Protein Kinase Plant Defense Response Pathway.
AB - An important problem in computational biology is the identification of potential
points of intervention that can lead to modified network behavior in a genetic
regulatory network. We consider the problem of deducing the effect of individual
genes on the behavior of the network in a statistical framework. In this article,
we make use of biological information from the literature to develop a Bayesian
network and introduce a method to estimate parameters of this network using data
that are relevant to the biological phenomena under study. Then, we give a novel
approach to select significant nodes in the network using a decision-theoretic
approach. The proposed method is applied to the analysis of the mitogen-activated
protein kinase pathway in the plant defense response to pathogens. Results from
applying the method to experimental data show that the proposed approach is
effective in selecting genes that play crucial roles in the biological phenomenon
being studied.
PMID- 27608181
TI - Review of the worldwide epidemiology of eating disorders.
PMID- 27608183
TI - Effect of restoring sinus rhythm in hypertensive patients with atrial
fibrillation undergoing electrical cardioversion.
AB - INTRODUCTION: Little is known about the effects of atrial fibrillation (AF) on
blood pressure (BP) levels in hypertensive patients. Some studies suggest a role
for rhythm control in managing such patients' BP, but the improvement observed in
cardiac performance after restoring sinus rhythm (SR) may coincide with an
increase in BP. The aim of this study was to apply ambulatory BP monitoring to
analyze BP changes in hypertensive patients after electrical cardioversion for
persistent AF. METHODS AND RESULTS: The study included 54 hypertensive patients
with persistent AF. Ambulatory BP monitoring was performed on the day before
electrical cardioversion and again about a month later under conditions of stable
medical treatment.Patients with a SR at follow-up (n=34) had significantly higher
24-h, night-time (P<0.05), and daytime (P=0.074) systolic BP, and significantly
lower 24-h, daytime (P<0.05), and night-time (P=0.078) DBP. The number of
patients with nocturnal dipping decreased from 20 to 14 and the number of those
with reverse dipping increased from 1 to 7. Patients with recurrent AF at follow
up (n=20) showed no significant BP changes, except for a decrease in the mean
night-time DBP. CONCLUSION: Restoring SR in hypertensive patients with AF led to
a significant increase in their systolic BP (especially at night) and a decrease
in their DBP. Hypertensive patients with AF should consequently undergo
ambulatory BP monitoring after electrical cardioversion for the purpose of
adjusting their antihypertensive treatment.
PMID- 27608182
TI - The use of ertapenem for the treatment of community-acquired pneumonia in routine
hospital practice: a matched cohort study.
AB - OBJECTIVE: The clinical response to ertapenem in community-acquired pneumonia
(CAP) at the setting of routine hospital practice has been scarcely evaluated.
METHODS: We retrospectively compared CAP cases treated with ertapenem or with
other standard antimicrobials (controls) at a tertiary 1,434-bed center from 2005
to 2014. RESULTS: Out of 6,145 patients hospitalized with CAP, 64 (1%) ertapenem
treated and 128 controls were studied (PSI IV-V 72%, mean age 73 years.). A
significant higher proportion of bedridden patients (41% vs. 21%), residence in
nursing homes (19% vs. 7%), previous use of antibiotics (39% vs. 29%) and
necrotizing (13% vs. 1%) or complicated (36% vs. 19%) pneumonia, was observed in
the ertapenem vs. non-ertapenem patients. Initial treatment with ertapenem was
independently associated with an earlier resolution of signs of infection. In
patients aged 65 or older the independent risks factors for mortality were: PSI
score (7.0, 95%CI 1.8-27.7), bedridden status (4.6, 95%CI 1.1-20.9) and Health
Care Associated Pneumonia (HCAP) (4.6, 95%CI 1.3-16.5). First-line treatment with
ertapenem was an independent protector factor in this subgroup of patients (0.1,
95%CI 0.1-0.7). CONCLUSIONS: Ertapenem showed a superior clinical response in
frail elderly patients with complicated community-acquired pneumonia, and it may
be considered as a first-line therapeutic regimen in this setting.
PMID- 27608184
TI - First assessment on the molecular phylogeny and phylogeography of the species
Gnaptor boryi distributed in Greece (Coleoptera: Tenebrionidae).
AB - The genus Gnaptor Brulle, 1983 (Blaptini, Gnaptorina) occurs in southeast Europe
as well as in Asiatic regions. As regards its taxonomy, four morphological
species have been attributed: Gnaptor boryi, G. prolixus, G. spinimanus and G.
medvedevi. Here, we use two different mitochondrial genetic markers (16S and
cytochrome c oxidase subunit 1 (COI)) in order to investigate the relationships
between the populations of the species G. boryi in Greece, compare them with the
current taxonomy and conjecture about its biogeographic history. In total, 29
specimens (28 G. boryi and one G. prolixus) were analyzed using maximum
likelihood and Bayesian inference methods. Our results clarified the presence of
three well-supported lineages: two belongs to G. boryi and one to G. prolixus.
The first diversification of these lineages started in the Late Miocene at 9 Mya
with the split of G. prolixus from Turkey and the second major split occurred in
the Early Pliocene at 3.7 Mya between the two lineages of G. boryi distributed
separately in northern Greece and Peloponnesos. According to Statistical
Dispersal - Vicariance Analysis and dispersal-extinction-cladogenesis analysis
analyses, vicariance seems to be the biogeographic event responsible for the
divergence of the two major lineages of G. boryi.
PMID- 27608185
TI - Effects of Electropolymerization Parameters of PPy(DBS) Surfaces on the Droplet
Flattening Behaviors During Redox.
AB - We present a systematic study on the effects of electropolymerization parameters
of polypyrrole-dodecylbenzenesulfonate (PPy(DBS)) surfaces on the flattening
behaviors of organic droplets during reduction and oxidation (redox). PPy(DBS)
surfaces were fabricated under varying electropolymerization conditions,
including voltage, surface charge density, and dopant electrolyte (DBS-)
concentration. The flattening behaviors on different PPy(DBS) surfaces were
characterized by analyzing droplet behaviors and energy-dispersive X-ray
spectroscopy (EDS) data. The surface charge density and voltage during
electropolymerization determined the thickness and doping ratio of synthesized
PPy(DBS) surfaces, affecting how DBS- molecules are released from PPy(DBS) upon
reduction. The release amount and rate of DBS- molecules were strongly related to
the droplet flattening time.
PMID- 27608187
TI - Isolated adrenocorticotropic hormone deficiency associated with nivolumab
therapy.
PMID- 27608186
TI - Action Enhances Acoustic Cues for 3-D Target Localization by Echolocating Bats.
AB - Under natural conditions, animals encounter a barrage of sensory information from
which they must select and interpret biologically relevant signals. Active
sensing can facilitate this process by engaging motor systems in the sampling of
sensory information. The echolocating bat serves as an excellent model to
investigate the coupling between action and sensing because it adaptively
controls both the acoustic signals used to probe the environment and movements to
receive echoes at the auditory periphery. We report here that the echolocating
bat controls the features of its sonar vocalizations in tandem with the
positioning of the outer ears to maximize acoustic cues for target detection and
localization. The bat's adaptive control of sonar vocalizations and ear
positioning occurs on a millisecond timescale to capture spatial information from
arriving echoes, as well as on a longer timescale to track target movement. Our
results demonstrate that purposeful control over sonar sound production and
reception can serve to improve acoustic cues for localization tasks. This finding
also highlights the general importance of movement to sensory processing across
animal species. Finally, our discoveries point to important parallels between
spatial perception by echolocation and vision.
PMID- 27608188
TI - Alpha-Helical Fragaceatoxin C Nanopore Engineered for Double-Stranded and Single
Stranded Nucleic Acid Analysis.
AB - Nanopores are used in single-molecule DNA analysis and sequencing. Herein, we
show that Fragaceatoxin C (FraC), an alpha-helical pore-forming toxin from an
actinoporin protein family, can be reconstituted in sphingomyelin-free standard
planar lipid bilayers. We engineered FraC for DNA analysis and show that the
funnel-shaped geometry allows tight wrapping around single-stranded DNA (ssDNA),
resolving between homopolymeric C, T, and A polynucleotide stretches. Remarkably,
despite the 1.2 nm internal constriction of FraC, double-stranded DNA (dsDNA) can
translocate through the nanopore at high applied potentials, presumably through
the deformation of the alpha-helical transmembrane region of the pore. Therefore,
FraC nanopores might be used in DNA sequencing and dsDNA analysis.
PMID- 27608189
TI - Highlights of Recent Findings on Quality-of-Life Management for Patients With
Cancer and Their Survivors.
PMID- 27608193
TI - Prevalence of Noninfectious Uveitis in the United States: A Claims-Based
Analysis.
AB - Importance: Noninfectious uveitis (NIU) is a collection of intraocular
inflammatory disorders that may be associated with significant visual impairment.
To our knowledge, few studies have investigated NIU prevalence overall or
stratified by inflammation location, severity, presence of systemic conditions,
age, or sex. Objective: To estimate NIU prevalence using a large, retrospective,
administrative claims database. Design, Setting, and Participants: This analysis
used the OptumHealth Reporting and Insights database to estimate 2012 NIU
prevalence. Analysis was conducted in September 2016. The large administrative
insurance claims database includes 14 million privately insured individuals in 69
self-insured companies spanning diverse industries. Included in the study were
patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and
continuous enrollment in a health plan for all of 2012 and categorized by
inflammation site. Main Outcomes and Measures: We estimated overall NIU
prevalence by inflammation site, severity, sex, and age. Patients with anterior
NIU were categorized by the presence of systemic conditions. Results: Of the
approximately 4 million eligible adult patients, approximately 2.1 million were
women, and of the 932 260 children, 475 481 were boys. The adult prevalence of
NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU
prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted
for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and
75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The
prevalences of noninfectious intermediate, posterior, and panuveitis were, for
adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7)
per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3
(95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The
prevalence of NIU increased with age and was higher among adult females than
males. Application of these estimates to the US population suggests that NIU
affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21
879 children (95% CI, 19 360-24 626) in 2015. Conclusions and Relevance: The
estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5
124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was
estimated using administrative claims from a commercially insured population,
which may have a different prevalence than other segments of the US population. A
better understanding of the prevalence of NIU will help to determine the number
of patients affected.
PMID- 27608194
TI - The Connection Between Thwarted Belongingness, Alcohol Consumption, Suicidal, and
Homicidal Ideation in a Criminal Justice Sample.
AB - BACKGROUND: To determine if thwarted belongingness in combination with frequent
alcohol use increased suicidal and homicidal ideation when known predictors were
controlled for (eg, depressive disorders, anxiety disorders, drug use, race, sex,
age, and employment status). METHOD: This study utilized an archival database.
Participants were 574 individuals at an outpatient substance abuse treatment
facility who were under community corrections supervision. The average age was
34.5 (SD = 10.9) years; there were 371 (64.6%) men and 287 (50.0%) Black
participants. Data were originally gathered from face-to-face interviews with the
participants by their case manager or an intake specialist when they entered
treatment. Self-reported suicidal and homicidal ideation was used as a dependent
variable in unadjusted and adjusted binary logistic regressions to determine the
influence of thwarted belongingness and frequent alcohol use. RESULTS: Thwarted
belongingness alone (ie, without frequent alcohol use) was associated with risk
for suicidal ideation, and was approaching significance for homicidal ideation.
The combination of thwarted belongingness and frequent alcohol use was associated
with the greatest risk for suicidal and homicidal ideation. Cocaine use and
employment status were also identified as significant predictors for suicidal and
homicidal ideation in the fully adjusted models. CONCLUSIONS: Thwarted
belongingness in combination with frequent alcohol use seems to have a large and
meaningful relationship with both suicidal and homicidal ideation. Additional
research is needed to better understand the relationship between alcohol,
thwarted belongingness, and outcomes such as suicide and homicide.
PMID- 27608195
TI - The Trajectory of Pharmacology Education in Dentistry: Is a Course Correction
Needed?
AB - In effort to stem the opioid epidemic, the authors of this editorial urge reforms
for dental training by returning to the basics. This near abandonment of
foundational sciences by stakeholders is at a high price: compromised patient
safety and health.
PMID- 27608196
TI - Use of a 10,600-nm CO2 Laser Mandibular Vestibular Extension in a Patient With a
Chromosomal Abnormality.
AB - Vestibuloplasty involves a series of surgical procedures designed to restore
alveolar ridge height by lowering the muscles attached to the buccal, labial, and
lingual aspects of the jaws. The technique is indicated in cases of insufficient
vestibular depth that may result from atrophy of the alveolar ridge and/or high
attachment of muscle or movable mucosa. This article focuses on a carbon dioxide
(CO2) laser vestibular extension procedure performed in a patient with
Klinefelter syndrome, which is caused by a chromosomal abnormality. The 10,600-nm
CO2 laser is shown to offer several advantages over a conventional scalpel and
other laser wavelengths for soft-tissue pre-prosthetic surgery, including
vestibular extension.
PMID- 27608197
TI - Single-Rooted Extraction Sockets: Classification and Treatment Protocol.
AB - Clinicians have many treatment techniques from which to choose when extracting a
failing tooth and replacing it with an implant-supported restoration and when
successful management of an extraction socket during the course of tooth
replacement is necessary to achieve predictable and esthetic outcomes. This
article presents a straightforward, yet thorough, classification for extraction
sockets of single-rooted teeth and provides guidance to clinicians in the
selection of appropriate and predictable treatment. The presented classification
of extraction sockets for single-rooted teeth focuses on the topography of the
extraction socket, while the protocol for treatment of each socket type factors
in the shape of the remaining bone, the biotype, and the location of the socket
whether it be in the mandible or maxilla. This system is based on the biologic
foundations of wound healing and can help guide clinicians to successful
treatment outcomes.
PMID- 27608198
TI - Proposed Guideline Revisions for Dental Sedation and General Anesthesia: Why
Target the Safest Level of Sedation?
AB - Recently proposed revisions to the American Dental Association's Guidelines for
the Use of Sedation and General Anesthesia by Dentists, aimed at improving safety
in dental offices, differentiate between levels of sedation based on drug-induced
changes in physiologic and behavioral states. However, the author of this op-ed
is concerned the proposed revisions may have far-reaching and unintended
consequences.
PMID- 27608199
TI - Zirconia-Prefabricated Crowns for Pediatric Patients With Primary Dentition:
Technique and Cementation for Esthetic Outcomes.
AB - Traditionally, many clinicians tend to forego esthetic considerations when full
coverage restorations are indicated for pediatric patients with primary
dentitions. However, the availability of new zirconia pediatric crowns and
reliable techniques for cementation makes esthetic outcomes practical and
consistent when restoring primary dentition. Two cases are described: a 3-year
old boy who presented with severe early childhood caries affecting both anterior
and posterior teeth, and a 6-year-old boy who presented with extensive caries of
his primary posterior dentition, including a molar requiring full coverage. The
parents of both boys were concerned about esthetics, and the extent of decay
indicated the need for full-coverage restorations. This led to the boys receiving
treatment using a restorative procedure in which the carious teeth were prepared
for and restored with esthetic tooth-colored zirconia crowns. In both cases,
comfortable function and pleasing esthetics were achieved.
PMID- 27608200
TI - Staged Reconstruction for a Severely Worn Dentition.
AB - When patients are constrained financially to receive dental work, a staged
approach can be an effective way for enabling treatment to proceed. In this case,
a patient who had been in the practice for about 10 years and had a severely worn
and eroded dentition finally opted to receive treatment in stages. A systematic
approach was used to determine the proper postoperative position of the teeth.
The subsequent treatment plan included the use of porcelain onlays and full
coverage crowns in the mandibular posterior along with provisional direct
composite restorations in the maxillary dentition; the composites would be
transitioned to porcelain crowns as the patient's finances would allow.
PMID- 27608201
TI - Structure and properties of phosphorene-like IV-VI 2D materials.
AB - Because of the excellent physical and chemical properties of phosphorene,
phosphorene and phosphorene-like materials have attracted extensive attention.
Since phosphorus belongs to group V, some group IV-VI compounds could also form
phosphorene-like configurations. In this work, GeO, SnO, GeS, and SnS monolayers
were constructed to investigate the structural and electronic properties by
employing first-principles computations. Phonon spectra suggest that these
monolayers are dynamically stable and could be realized in experiments. These
monolayers are all semiconductors with the band gaps of 2.26 ~ 4.13 eV. Based on
the monolayers, GeO, SnO, GeS, and SnS bilayers were also constructed. The band
gaps of these bilayers are smaller than those of the corresponding monolayers.
Moreover, the optical properties of these monolayers and bilayers were
calculated, and the results indicate that the SnO, GeS and SnS bilayers exhibit
obvious optical absorption in the visible spectrum. All the results suggest that
phosphorene-like IV-VI materials are promising candidates for electronic and
optical devices.
PMID- 27608202
TI - Clinicopathologic study of 90 cases of trichofolliculoma.
PMID- 27608203
TI - Hexanuclear Platinum(II) Thiolate Macrocyclic Host: Charge-Transfer-Driven
Inclusion of a Ag(I) Ion Guest.
AB - The inclusion of a Ag(I) ion by a hexanuclear platinum(II) thiolate macrocycle in
solution was demonstrated, and the inclusion structure was determined by X-ray
crystallography. Unique host-guest intermetallic interactions driven by charge
transfer were elucidated by optical absorption spectroscopy and theoretical
calculations.
PMID- 27608204
TI - A Novel Reconstruction to Maintain Cupid's Bow.
PMID- 27608205
TI - Double-Blind, Placebo-Controlled Pilot Study on the Use of Platelet-Rich Plasma
in Women With Female Androgenetic Alopecia.
AB - BACKGROUND: Platelet-rich plasma (PRP) has been suggested as a therapeutic
intervention for female androgenetic alopecia. OBJECTIVE: To perform a pilot
study on the effect of PRP scalp injections in women with female androgenetic
alopecia. MATERIALS AND METHODS: This double-blind, multicenter, placebo
controlled study compared the effect of PRP with that of saline placebo as scalp
injection. The endpoints were hair count and hair mass index (HMI), along with
patient-opinion survey responses. Platelet-rich plasma was manufactured from
patients' blood using the Angel PRP system. RESULTS: Hair mass index or hair
count did not statistically significantly differ between the study and placebo
groups. However, 13.3% of the treatment subjects (vs 0% of the placebo subjects)
experienced substantial improvement in hair loss, rate of hair loss, hair
thickness, and ease of managing/styling hair, and 26.7% (vs 18.2% of the placebo
group) reported that their hair felt coarser or heavier after the treatment.
CONCLUSION: Platelet-rich plasma failed to demonstrate any statistically
significant improvement in HMI or hair count in women with congenital female
pattern hair loss. The patient survey results suggest a therapeutic advantage of
PRP as perceived by patients but not according to hair count or HMI.
PMID- 27608206
TI - Clinical and Histologic Effects of Fractional Microneedling Radiofrequency
Treatment on Rosacea.
AB - BACKGROUND: Fractional microneedling radiofrequency (FMR) is an emerging
treatment modality, but its effect on rosacea has not been studied yet.
OBJECTIVE: To investigate the potential impact of FMR treatment on clinical
improvement and histologic changes in rosacea patients. MATERIALS AND METHODS: A
12-week, prospective, randomized, split-face clinical trial was conducted. Two
sessions of FMR were performed on one side of the cheeks with 4-week interval and
the other side remained untreated. Erythema index from DermaSpectrometer and a*
value from Spectrophotometer CM-2002 were measured at each visit for the
objective measurement of erythema. Histologic analysis of skin samples was also
carried out. RESULTS: Clinical evaluation and photometric measurement revealed
the reduction of redness in the treated side compared with untreated side and
baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12
compared with baseline. Reduced expression of markers related to inflammation,
innate immunity, and angiogenesis was observed in immunohistochemical staining of
tissue obtained after FMR treatment. CONCLUSION: Fractional microneedling
radiofrequency treatment showed modest clinical and histologic improvement of
rosacea, and it might be used as an alternative or in combination with other
treatment methods.
PMID- 27608207
TI - Plaque-Like Dermatofibroma With Satellitosis.
PMID- 27608208
TI - A Review of Local Anesthetics: Minimizing Risk and Side Effects in Cutaneous
Surgery.
AB - BACKGROUND: The specialty of dermatology relies heavily on local anesthesia for
diagnosis and management of skin disease. The appropriate selection, preparation,
administration, and monitoring of these medications affect surgical outcome and
patient safety and satisfaction. OBJECTIVE: To perform a comprehensive literature
review of the side effects and risks associated with local anesthetics used in
cutaneous surgery. Current recommendations to reduce risk and minimize side
effects are reviewed. MATERIALS AND METHODS: A comprehensive review of the
English-language medical literature search was performed. RESULTS: No current
review articles of the side effects and risks of local anesthetics were
identified. This review serves to discuss local anesthetics commonly used in
dermatology and cutaneous surgery along with practical information regarding
prevention of adverse outcomes and addressing local and systemic reactions when
they arise. CONCLUSION: Local anesthetics commonly used in cutaneous surgery have
potential risks and side effects. Appropriate selection and utilization of local
anesthetics and knowledge of the means to prevent and address these risks can
impact surgical outcomes, patient satisfaction and safety, and ultimately patient
experience in the dermatology clinic.
PMID- 27608262
TI - Role of the Medical Examiner in Zika Virus and Other Emerging Infections.
AB - CONTEXT: -Medical examiners and coroners have long been an integral component of
public health, often being the first to recognize and describe emerging
infectious diseases. Given their experience and access, medical examiners and
coroners will provide valuable contributions to better understanding Zika virus
infection and its sequelae. OBJECTIVE: -To review past examples of medical
examiner/coroner involvement in recognition of emerging infectious diseases and
describe how medical examiners and coroners will be critical in understanding the
pathophysiology of Zika infections. DESIGN: -Review of the existing literature on
the role of medical examiners and coroners in the identification of emergent
infections and the available literature on Zika virus. RESULTS: -Medical
examiners and coroners have played a crucial role in identifying numerous
emerging infectious diseases such as hantavirus pulmonary syndrome and West Nile
virus, and have the expertise and experience to aid in elucidating the
pathophysiologic effects of Zika virus and tracking its distribution and risk
factors. CONCLUSIONS: -Medical examiners and coroners will be a significant
factor in the unified public health approach needed to mitigate the effects of
Zika virus and other, heretofore unrecognized, infectious diseases.
PMID- 27608263
TI - Descriptive epidemiology of Escherichia coli bacteraemia in England, April 2012
to March 2014.
AB - We determined the incidence, risk factors and antimicrobial susceptibility
associated with Escherichia coli bacteraemia in England over a 24 month period.
Case data were obtained from the national mandatory surveillance database, with
susceptibility data linked from LabBase2, a voluntary national microbiology
database. Between April 2012 and March 2014, 66,512 E. coli bacteraemia cases
were reported. Disease incidence increased by 6% from 60.4 per 100,000 population
in 2012-13 to 63.5 per 100,000 population in 2013-14 (p < 0.0001). Rates of E.
coli bacteraemia varied with patient age and sex, with 70.5% (46,883/66,512) of
cases seen in patients aged >= 65 years and 52.4% (33,969/64,846) of cases in
females. The most common underlying cause of bacteraemia was infection of the
genital/urinary tract (41.1%; 27,328/66,512), of which 98.4% (26,891/27,328) were
urinary tract infections (UTIs). The majority of cases (76.1%; 50,617/66,512) had
positive blood cultures before or within two days of admission and were
classified as community onset cases, however 15.7% (10,468/66,512) occurred in
patients who had been hospitalised for over a week. Non-susceptibility to
ciprofloxacin, third-generation cephalosporins, piperacillin-tazobactam,
gentamicin and carbapenems were 18.4% (8,439/45,829), 10.4% (4,256/40,734), 10.2%
(4,694/46,186), 9.7% (4,770/49,114) and 0.2% (91/42,986), respectively.
Antibiotic non-susceptibility was higher in hospital-onset cases than for those
presenting from the community (e.g. ciprofloxacin non-susceptibility was 22.1%
(2,234/10,105) for hospital-onset vs 17.4% (5,920/34,069) for community-onset
cases). Interventions to reduce the incidence of E. coli bacteraemia will have to
target the community setting and UTIs if substantial reductions are to be
realised.
PMID- 27608265
TI - Is Nematocharax (Actinopterygii, Characiformes) a monotypic fish genus?
AB - The combination of DNA barcodes and geometric morphometrics is useful to
discriminate taxonomically controversial species, providing more precise
estimates of biodiversity. Therefore, our goal was to assess the genetic and
morphometric diversity in Nematocharax, a controversial monotypic and sexually
dimorphic genus of Neotropical fish, based on sequencing of cytochrome c oxidase
subunit I (COI) and morphometric analyses in seven populations of N. venustus
from coastal rivers in Brazil. The average pairwise intrapopulation divergence in
COI ranged from 0 to 2.2%, while the average pairwise interpopulation divergence
varied from 0 to 7.5%. The neighbour-joining (NJ) tree resulted in five genetic
groups (bootstrap >= 97%), which correspond to the five clusters delimited by the
BIN System, GMYC, and bPTP, indicating that there might be at least five species
(or OTUs) within Nematocharax. Morphometric differences among these genetic
lineages were also identified. Apparently, sexual selection, restricted
dispersal, and geographic isolation might have acted synergistically to cause the
evolutionary split of populations. These data challenge the current view that
Nematocharax is a monotypic genus inasmuch as evolutionarily significant units or
even distinguished species were identified. Therefore, we recommend that the
highly impacted coastal basins in northeastern Brazil should be prioritized in
conservation plans.
PMID- 27608264
TI - Sexual Behaviors Linked to Drug and Alcohol Use Among Men Who Have Sex With Men
in China.
AB - BACKGROUND: High-risk sexual behaviors drive the HIV epidemic among men who have
sex with men (MSM). Alcohol consumption and use of club drugs may increase sexual
risk behaviors. We evaluated effects of drug and alcohol use on sexual behaviors
with both their male and female partners as well as on HIV and syphilis
infections among MSM in China. METHODS: As the part of a community randomized
clinical trial that conducted among MSM in Beijing from 2013 to 2015, we
recruited a total of 3,680 participants cross-sectionally. A self-administered
questionnaire was employed to collect information regarding demographics, sexual
behaviors, and a history of alcohol and drug use. Blood sample was collected for
HIV and syphilis testing. RESULTS: A total of 3,588 MSM completed the survey and
were included in the data analysis. The mean age was 29.9 with 97.3% of Han
ethnicity and 85.0% unmarried. The HIV and syphilis prevalence was 12.7% and
7.4%, respectively. Drug use was significantly associated with higher odds of HIV
infection (aOR = 1.3, 95% Confidence Interval [CI] = 1.0,1.6), but not associated
with syphilis. A higher level of alcohol consumption was similarly associated
with higher odds of HIV risks with both male (e.g., condomless sex acts) and
female partners (e.g., numbers of sexual partners). CONCLUSION: The association
between drug and alcohol use and high-risk behaviors is notable among MSM in
China. Integrated HIV interventions that target substance use among MSM may be
more effective than programs that only target HIV alone.
PMID- 27608267
TI - Anisotropic extended misfit dislocations in overcritical SiGe films by local
substrate patterning.
AB - In this work we will show how local substrate patterning leads to a long range
controlled propagation of dislocations in SiGe films grown on Si(001) substrates.
Dislocations preferentially nucleate in the inhomogeneous strain field associated
with the patterned pits, and then partialize on the local (111) surfaces which
form the pit sidewalls. The resulting V-shaped defects extend for several microns
and effectively block the propagation of randomly nucleated dislocations which
propagate in the perpendicular direction. The surface morphology and strain
fields associated with the extended defects have been characterized by atomic
force microscopy and MURaman spectroscopy, and the defects have been directly
observed with high resolution transmission electron microscopy.
PMID- 27608266
TI - Structural and Functional Properties of Soy Protein Isolates Modified by Soy
Soluble Polysaccharides.
AB - Aiming to achieve the modification to soy protein isolate (SPI) by soy soluble
polysaccharides (SSPS), electrically driven complex systems were first
established in the environment of pH 3.0, and then reconstituted SPI particles
with different SPI-SSPS ratios were obtained under freeze-drying process. Through
this treatment, the structures of SPI particles were partly unfolded and adsorbed
SSPS mainly via hydrophobic interactions and hydrogen bonding with larger
particle sizes. The adherence of SSPS decreased the surface hydrophobicity of
reconstituted SPI particles, but exerted not much influence on the emulsifying
and foaming activities and increased the corresponding stabilities due to
enhancing the unfolded extent of structure and improving the conformation
flexibility. Reconstituted SPI-SSPS particles might rearrange and link each other
due to the presence of SSPS on the air-water interface to better stabilize these
systems. At SPI-SSPS ratio of 10:1, lower temperature was required to form gels
with lower gel intensity and porous structure. The findings provide a further
comprehension to the relationship between structures and functional properties of
SPI modified by SSPS and the feasibility of applying these reconstituted
particles to needed areas.
PMID- 27608268
TI - The devil always experienced malicious pleasure in imposing himself in
neuropsychiatric nosology.
PMID- 27608269
TI - A new removable airway stent.
AB - BACKGROUND: Malignant airway obstruction is a feared complication and will most
probably occur more frequently in the future because of increasing cancer
incidence and increased life expectancy in cancer patients. Minimal invasive
treatment using airway stents represents a meaningful and life-saving palliation.
We present a new removable airway stent for improved individualised treatment.
METHODS: To our knowledge, the new airway stent is the world's first knitted and
uncovered self-expanding metal stent, which can unravel and be completely
removed. In an in vivo model using two anaesthetised and spontaneously breathing
pigs, we deployed and subsequently removed the stents by unravelling the device.
The procedures were executed by flexible bronchoscopy in an acute and a chronic
setting - a 'proof-of-principle' study. RESULTS: The new stent was easily and
accurately deployed in the central airways, and it remained fixed in its original
position. It was easy to unravel and completely remove from the airways without
clinically significant complications. During the presence of the stent in the
chronic study, granulation tissue was induced. This tissue disappeared
spontaneously with the removal. CONCLUSIONS: The new removable stent functioned
according to its purpose and unravelled easily, and it was completely removed
without significant technical or medical complications. Induced granulation
tissue disappeared spontaneously. Further studies on animals and humans are
needed to define its optimal indications and future use.
PMID- 27608270
TI - Prevalence of abnormal findings when adopting new national and international
Global Lung Function Initiative reference values for spirometry in the Finnish
general population.
AB - BACKGROUND: New Finnish (Kainu2015) and international Global Lung Function
Initiative (GLI2012) reference values for spirometry were recently published. The
aim of this study is to compare the interpretative consequences of adopting these
new reference values with older, currently used Finnish reference values
(Viljanen1982) in the general population of native Finns. METHODS: Two Finnish
general population samples including 1,328 adults (45% males) aged 21-74 years
were evaluated. Airway obstruction was defined as a reduced ratio of forced
expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible
restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced
FEV1 below their respective 2.5th percentiles. The severity gradings of reduced
lung function were also compared. RESULTS: Using the Kainu2015 reference values,
the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it
was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was
found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the
Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8,
4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively.
CONCLUSIONS: The application of the GLI2012 reference values underestimates the
prevalence of abnormal spirometric findings in native Finns. The adoption of the
Kainu2015 reference values reduces the prevalences of airways obstruction,
decreased ventilatory capacity, and restrictive impairment by approximately 50%.
Changing from the 2.5th percentile, the previously used lower limit of normal, to
the 5th percentile recommended by the American Thoracic Society/European
Respiratory Society will not increase the prevalence of abnormal findings in the
implementation of spirometry reference values.
PMID- 27608272
TI - High-Performance, Simplified Fluorescence and Phosphorescence Hybrid White
Organic Light-Emitting Devices Allowing Complete Triplet Harvesting.
AB - Causes of efficiency limitation in common fluorescence and phosphorescence hybrid
white organic light-emitting devices (WOLEDs) are discussed, and a new device
architecture is proposed to address these issues. This architecture employs a
fluorescent emitting layer (EML) of blue exciplex-forming cohost, which shows
broad and strong thermally activated delayed fluorescence (TADF). Hybrid WOLEDs
based on this architecture not only allow complete triplet harvesting for light
generation but also can achieve white light emission with high color rending
indexes (CRI) using only two colors. By using 26DCzPPy:PO-T2T as the blue
fluorescent EML and 26DCzPPy:Ir complexes as the phosphorescent EML, we prepared
a series of two-color WOLEDs with low turn-on voltages of 2.5-3.3 V, high forward
viewing EQEs of 12.7-19.3% and high CRIs of 67-77. These results suggest this new
architecture would be an effective way to achieve high performance WOLEDs with
simple structures.
PMID- 27608271
TI - Prolonged partial upper airway obstruction during sleep - an underdiagnosed
phenotype of sleep-disordered breathing.
AB - Obstructive sleep apnea syndrome (OSAS) is a well-recognized disorder
conventionally diagnosed with an elevated apnea-hypopnea index. Prolonged partial
upper airway obstruction is a common phenotype of sleep-disordered breathing
(SDB), which however is still largely underreported. The major reasons for this
are that cyclic breathing pattern coupled with arousals and arterial
oxyhemoglobin saturation are easy to detect and considered more important than
prolonged episodes of increased respiratory effort with increased levels of
carbon dioxide in the absence of cycling breathing pattern and repetitive
arousals. There is also a growing body of evidence that prolonged partial
obstruction is a clinically significant form of SDB, which is associated with
symptoms and co-morbidities which may partially differ from those associated with
OSAS. Partial upper airway obstruction is most prevalent in women, and it is
treatable with the nasal continuous positive pressure device with good adherence
to therapy. This review describes the characteristics of prolonged partial upper
airway obstruction during sleep in terms of diagnostics, pathophysiology,
clinical presentation, and comorbidity to improve recognition of this phenotype
and its timely and appropriate treatment.
PMID- 27608273
TI - Asymmetric Synthesis of an Amino Acid Derivative from Achiral Aroyl Acrylamide by
Reversible Michael Addition and Preferential Crystallization.
AB - Single-handed alpha-amino acid derivatives were generated from achiral precursors
without an external chiral source. Conjugate addition of phenethylamine to an
achiral aroyl acrylamide under homogeneous conditions gave the alpha-amino amides
in quantitative yields, which crystallized as a conglomerate of a P21 crystal
system. Dynamic preferential crystallization or attrition-enhanced deracemization
resulted in the formation of enantiomorphic crystals of 99 % ee.
PMID- 27608274
TI - Hydrogen-Bonded Homoleptic Fluoride-Diarylurea Complexes: Structure, Reactivity,
and Coordinating Power.
AB - Hydrogen bonding with fluoride is a key interaction encountered when analyzing
the mode of action of 5'-fluoro-5'-deoxyadenosine synthase, the only known enzyme
capable of catalyzing the formation of a C-F bond from F-. Further understanding
of the effect of hydrogen bonding on the structure and reactivity of complexed
fluoride is therefore important for catalysis and numerous other applications,
such as anion supramolecular chemistry. Herein we disclose a detailed study
examining the structure of 18 novel urea-fluoride complexes in the solid state,
by X-ray and neutron diffraction, and in solution phase and explore the
reactivity of these complexes as a fluoride source in SN2 chemistry. Experimental
data show that the structure, coordination strength, and reactivity of the urea
fluoride complexes are tunable by modifying substituents on the urea receptor.
Hammett analysis of aryl groups on the urea indicates that fluoride binding is
dependent on sigmap and sigmam parameters with stronger binding being observed
for electron-deficient urea ligands. For the first time, defined urea-fluoride
complexes are used as fluoride-binding reagents for the nucleophilic substitution
of a model alkyl bromide. The reaction is slower in comparison with known alcohol
fluoride complexes, but SN2 is largely favored over E2, at a ratio surpassing all
hydrogen-bonded complexes documented in the literature for the model alkyl
bromide employed. Increased second-order rate constants at higher dilution
support the hypothesis that the reactive species is a 1:1 urea-fluoride complex
of type [UF]- (U = urea) resulting from partial dissociation of the parent
compound [U2F]-. The dissociation processes can be quantified through a
combination of UV and NMR assays, including DOSY and HOESY analyses that
illuminate the complexation state and H-bonding in solution.
PMID- 27608276
TI - Split-GFP: SERS Enhancers in Plasmonic Nanocluster Probes.
AB - The assembly of plasmonic metal nanoparticles into hot spot surface-enhanced
Raman scattering (SERS) nanocluster probes is a powerful, yet challenging
approach for ultrasensitive biosensing. Scaffolding strategies based on self
complementary peptides and proteins are of increasing interest for these
assemblies, but the electronic and the photonic properties of such hybrid
nanoclusters remain difficult to predict and optimize. Here, split-green
fluorescence protein (sGFP) fragments are used as molecular glue and the GFP
chromophore is used as a Raman reporter to assemble a variety of gold
nanoparticle (AuNP) clusters and explore their plasmonic properties by numerical
modeling. It is shown that GFP seeding of plasmonic nanogaps in AuNP/GFP hybrid
nanoclusters increases near-field dipolar couplings between AuNPs and provides
SERS enhancement factors above 108 . Among the different nanoclusters studied,
AuNP/GFP chains allow near-infrared SERS detection of the GFP chromophore
imidazolinone/exocyclic C?C vibrational mode with theoretical enhancement factors
of 108 -109 . For larger AuNP/GFP assemblies, the presence of non-GFP seeded
nanogaps between tightly packed nanoparticles reduces near-field enhancements at
Raman active hot spots, indicating that excessive clustering can decrease SERS
amplifications. This study provides rationales to optimize the controlled
assembly of hot spot SERS nanoprobes for remote biosensing using Raman reporters
that act as molecular glue between plasmonic nanoparticles.
PMID- 27608277
TI - Reversible Assembly of Graphitic Carbon Nitride 3D Network for Highly Selective
Dyes Absorption and Regeneration.
AB - Responsive assembly of 2D materials is of great interest for a range of
applications. In this work, interfacial functionalized carbon nitride (CN)
nanofibers were synthesized by hydrolyzing bulk CN in sodium hydroxide solution.
The reversible assemble and disassemble behavior of the as-prepared CN nanofibers
was investigated by using CO2 as a trigger to form a hydrogel network at first.
Compared to the most widespread absorbent materials such as active carbon,
graphene and previously reported supramolecular gel, the proposed CN hydrogel not
only exhibited a competitive absorbing capacity (maximum absorbing capacity of
methylene blue up to 402 mg/g) but also overcame the typical deficiencies such as
poor selectivity and high energy-consuming regeneration. This work would provide
a strategy to construct a 3D CN network and open an avenue for developing smart
assembly for potential applications ranging from environment to selective
extraction.
PMID- 27608275
TI - Cardiotrophin-1 Regulates Adipokine Production in 3T3-L1 Adipocytes and Adipose
Tissue From Obese Mice.
AB - Cardiotrophin-1 (CT-1) belongs to the IL-6 family of cytokines. Previous studies
of our group revealed that CT-1 is a key regulator of glucose and lipid
metabolism. The aim of the present study was to analyze the in vitro and in vivo
effects of CT-1 on the production of several adipokines involved in body weight
regulation, nutrient metabolism, and inflammation. For this purpose, 3T3-L1
adipocytes were incubated with recombinant protein CT-1 (rCT-1) (1-40 ng/ml) for
1 and 18 h. Moreover, the acute effects of rCT-1 administration (0.2 mg/kg, i.v.)
for 30 min and 3 h on adipokines levels were also evaluated in high-fat fed obese
mice. In 3T3-L1 adipocytes, rCT-1 treatment downregulated the expression and
secretion of leptin, resistin, and visfatin. However, rCT-1 significantly
stimulated apelin mRNA and secretion. rCT-1 (18 h) also promoted the activation
by phosphorylation of AKT, ERK 1/2, and STAT3. Interestingly, pre-treatment with
the PI3K inhibitor LY294002 reversed the stimulatory effects of rCT-1 on apelin
expression, suggesting that this pathway could be mediating the effects of rCT-1
on apelin production. In contrast, acute administration of rCT-1 (30 min and 3 h)
to diet-induced obese mice downregulated leptin and resistin, without
significantly modifying apelin or visfatin mRNA in adipose tissue. Furthermore,
CT-1 null mice exhibited altered expression of adipokines in adipose tissue. The
present study demonstrates that rCT-1 modulates the production of adipokines in
vitro and in vivo, suggesting that the regulation of the secretory function of
adipocytes could be involved in the metabolic actions of this cytokine. J. Cell.
Physiol. 232: 2469-2477, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27608279
TI - Treating paediatric anterior glottic web: single-centre experience of 20 patients
with comparison among techniques.
PMID- 27608278
TI - Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
and Nasu-Hakola disease: lesion staging and dynamic changes of axons and
microglial subsets.
AB - The brains of 10 Japanese patients with adult onset leukoencephalopathy with
axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse
leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic
leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD)
and five age-matched Japanese controls were examined neuropathologically with
special reference to lesion staging and dynamic changes of microglial subsets. In
both diseases, the pathognomonic neuropathological features included spherically
swollen axons (spheroids and globules), axon loss and changes of microglia in the
white matter. In ALSP, four lesion stages based on the degree of axon loss were
discernible: Stage I, patchy axon loss in the cerebral white matter without
atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the
cerebral white matter and slight dilatation of the lateral ventricles; Stage III,
extensive axon loss in the cerebral white matter and dilatation of the lateral
and third ventricles without remarkable axon loss in the brainstem and
cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of
the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule
and pontine base were relatively well preserved in the N-HD, even at Stage IV,
and the swollen axons were larger with a higher density in the ALSP. Microglial
cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than
in N-HD, and the shape and density of the cells changed in each stage. With
progression of the stage, clinical symptoms became worse to apathetic state, and
epilepsy was frequently observed in patients at Stages III and IV in both
diseases. From these findings, it is concluded that (i) shape, density and
subsets of microglia change dynamically along the passage of stages and (ii)
increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of
axons in ALSP.
PMID- 27608280
TI - Fatigue and Sleep Among Employees With Prospective Increase in Work Time Control:
A 1-Year Observational Study With Objective Assessment.
AB - OBJECTIVES: This observational study aimed to determine how 1-year changes in
work time control (WTC) have an impact upon objectively measured fatigue and
sleep among employees. METHODS: Thirty-nine employees were divided into two
groups according to whether or not their WTC increased from baseline to 1 year
later. Psychomotor vigilance task (PVT) and wrist actigraphy were used to
objectively measure fatigue and sleep, respectively. Self-reported outcomes were
also measured. RESULTS: The increased WTC group showed gradual improvements in
PVT performance and sleep quality over the course of the follow-up period
compared with the not-increased WTC group. Between-group differences were
statistically significant for PVT lapses and tended to be significant for PVT
speed after 1 year. CONCLUSIONS: A progressive increase in WTC could play a
crucial role in reducing fatigue and promoting sleep among employees.
PMID- 27608281
TI - Evidence-based recommendations on the use of intravenous lipid emulsion therapy
in poisoning.
AB - BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat
life-threatening local anesthetic (LA) toxicity, its use has expanded to include
both non-local anesthetic (non-LA) poisoning and less severe manifestations of
toxicity. A collaborative workgroup appraised the literature and provides
evidence-based recommendations for the use of ILE in poisoning. METHODS:
Following a systematic review of the literature, data were summarized in four
publications: LA and non-LA poisoning efficacy, adverse effects, and analytical
interferences. Twenty-two toxins or toxin categories and three clinical
situations were selected for voting. Voting statements were proposed using a
predetermined format. A two-round modified Delphi method was used to reach
consensus on the voting statements. Disagreement was quantified using RAND/UCLA
Appropriateness Method. RESULTS: For the management of cardiac arrest, we
recommend using ILE with bupivacaine toxicity, while our recommendations are
neutral regarding its use for all other toxins. For the management of life
threatening toxicity, (1) as first line therapy, we suggest not to use ILE with
toxicity from amitriptyline, non-lipid soluble beta receptor antagonists,
bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine,
malathion but are neutral for other toxins, (2) as part of treatment modalities,
we suggest using ILE in bupivacaine toxicity if other therapies fail, but are
neutral for other toxins, (3) if other therapies fail, we recommend ILE for
bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs,
amitriptyline, and bupropion, but our recommendations are neutral for all other
toxins. In the treatment of non-life-threatening toxicity, recommendations are
variable according to the balance of expected risks and benefits for each toxin.
For LA-toxicity we suggest the use of Intralipid(r) 20% as it is the formulation
the most often reported. There is no evidence to support a recommendation for the
best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE
dosing and infusion duration due to insufficient data for non-LAs. All
recommendations were based on very low quality of evidence. CONCLUSION: Clinical
recommendations regarding the use of ILE in poisoning were only possible in a
small number of scenarios and were based mainly on very low quality of evidence,
balance of expected risks and benefits, adverse effects, laboratory interferences
as well as related costs and resources. The workgroup emphasizes that dose
finding and controlled studies reflecting human poisoning scenarios are required
to advance knowledge of limitations, indications, adverse effects, effectiveness,
and best regimen for ILE treatment.
PMID- 27608282
TI - Mirror, Mirror on the Roof!
PMID- 27608283
TI - Marcus Gunn Jaw-Winking Syndrome: A Comprehensive Review and Report of Four Novel
Cases.
AB - PURPOSE: To report 4 cases of Marcus Gunn jaw-winking synkinesis (MGJWS) in the
absence of ptosis. METHODS: A retrospective review of patients with MGJWS and
congenital ptosis was compiled from the public and private subspecialty adult and
pediatric oculoplastic practices of the 2 senior authors (AAM, TGH). Clinical
data collected on patients with MGJWS included visual acuity, stereopsis, ocular
motility, side of jaw-wink, presence or absence of ptosis, levator function,
clinical photographs and videos, and any management undertaken. RESULTS: A total
of 848 cases of congenital ptosis were seen. Of these, there were 72 consecutive
patients with MGJWS, of which 4 cases (5.6%) had no ptosis. One patient had
bilateral MGJWS, with ptosis on one side only. The authors found the incidence of
MGJWS in our study population to be 8.5% of all congenital ptosis cases. When the
authors excluded syndromic, neurogenic, and myopathic causes of congenital
ptosis, the incidence was 12.1%. In addition, the authors found a trend toward
females with simple congenital ptosis and MGJWS being affected on the left side,
however this was not statistically significant. CONCLUSIONS: The authors report
the first case series of MGJWS in the absence of ptosis within the second largest
series ever reported. These findings may help further our understanding of the
etiology behind MGJWS.
PMID- 27608284
TI - Conjunctival Squamous Cell Carcinoma With Orbital Extension.
PMID- 27608285
TI - A Single- Versus Double-Layered Closure Technique in Anophthalmic Surgery.
AB - PURPOSE: To compare the frequency of orbital implant exposure and extrusion
following eye removal with a simplified closure technique, closing Tenon's
capsule and conjunctiva in 1 layer versus the classic technique of closure in 2
separate layers. METHODS: The authors conducted a retrospective case note review
of patients who underwent evisceration or enucleation treated by 1 surgeon
between 2001 and 2013. Between 2001 and 2004, Tenon's capsule and conjunctiva
were closed in separate layers; after 2004, a simplified 1-layer closure
following eye removal was used. The primary outcome parameters were presence or
absence of implant exposure or extrusion. RESULTS: One hundred fifty-seven
patients who underwent evisceration and 172 patients who underwent enucleation
were included. Following evisceration, 2.5% developed exposure or extrusion of
the implant, this was 2.5% in the 1-layer closure technique and 2.7% in the 2
layer closure technique (p = 0.95). Following enucleation, 1.7% developed
exposure or extrusion of the implant, this was 1.8% in the 1-layer closure
technique and 1.7% in the 2-layer closure technique (p = 0.96). Overall implant
exposure and extrusion was 2.1%, this was 2.2% in the 1-layer closure technique
and 2.1% in the 2-layer closure technique (p = 0.96). CONCLUSIONS: No difference
was found in the frequency of spheric acrylic implant exposure or extrusion in
patients who underwent eye removal with single-layer closure of Tenon's capsule
and conjunctiva compared with patients treated with separate closure of these
layers.
PMID- 27608286
TI - Efficacy of Orbital Color Doppler Imaging and Neuroimaging in the Diagnosis of
Carotid Cavernous Fistulas.
AB - PURPOSE: To evaluate the diagnostic sensitivity and specificity of orbital color
Doppler imaging (CDI) and conventional neuroimaging (CT/MRI) compared with
cerebral angiography in patients with carotid-cavernous fistulas (CCFs). METHODS:
The study design was a retrospective patient chart and imaging review. The
authors reviewed 655 charts of all patients who underwent CDI and neuroimaging
(CT/MRI) between 2006 and 2015 at one institution. Sixty patients had a
presumptive diagnosis of CCF without thrombosis. Thirty-seven patients with 43
events met the inclusion criteria of the study. The diagnostic sensitivity of the
3 noninvasive imaging modalities (CDI, CT, MRI) for CCF was compared with the
gold standard 6-vessel cerebral angiography. Significance testing was performed
using the 2-tailed Fisher test. RESULTS: Color Doppler imaging had high
sensitivity (96.8%) but low specificity (41.7%) for the diagnosis of CCFs with
anterior orbital findings. A negative CDI had more diagnostic value than a
positive CDI. While an arterial wave form in the superior ophthalmic vein was the
most common finding of CCF on CDI, enlargement of the superior ophthalmic vein
was the only statistically significant finding. Posterior cortical venous
drainage was noted in about 10% of the patients with indirect (low-flow)
fistulas, who presented with unilateral orbital signs and symptoms, a finding not
previously reported in the literature. CONCLUSION: Color Doppler imaging is a
useful noninvasive, radiation-free modality for diagnosis of CCF with anterior
drainage, with higher sensitivity than CT or MRI, but equivalent specificity. A
significant limitation of CDI is the lack of usefulness in diagnosing fistulas
with posterior cortical venous drainage, which carry a risk of intracerebral
hemorrhage and stroke. In this series, 10% of unilateral CCFs with anterior
orbital signs and symptoms showed angiographic evidence of posterior cortical
venous drainage.
PMID- 27608287
TI - A Retrospective Review of Orbital Decompression for Thyroid Orbitopathy with
Endoscopic Preservation of the Inferomedial Orbital Bone Strut.
AB - PURPOSE: To determine incidence of new-onset diplopia, resolution of preexisting
diplopia, and impact on proptosis resulting from endoscopic orbital decompression
with and without preservation of the inferomedial orbital strut for thyroid
orbitopathy. METHODS: Retrospective review of all patients undergoing endoscopic
2- or 3-wall decompression with or without preservation of the strut for thyroid
orbitopathy from January 2012 to June 2015. RESULTS: Twenty-six patients (45
orbits) were included and divided into 4 primary categories: 2-wall decompression
with strut preservation (4 orbits, 8%), 2-wall decompression with strut removal
(7 orbits, 16%), 3-wall decompression with strut preservation (27 orbits, 60%),
and 3-wall decompression with strut removal (7 orbits, 16%). The incidence of new
onset diplopia was 20% (2/10 patients without preoperative diplopia) overall and
16% in the strut preservation group (1/6 patients without preoperative diplopia).
Resolution of diplopia occurred in 4 of 16 patients (25%) with preoperative
diplopia, and all 4 had been treated with a 3-wall decompression with strut
preservation. Resolution of diplopia in the group treated with strut preservation
was 36% (4/11 patients with preoperative diplopia), and 0% of the 5 diplopic
patients treated without strut preservation. Reduction in proptosis was
statistically greater in those treated with strut removal (p = 0.003).
CONCLUSIONS: This study demonstrates that endoscopic orbital decompression with
preservation of the inferomedial bone strut results in a comparable to lower rate
of new-onset diplopia compared with other reported techniques. When combined with
3-wall balanced decompression, this technique demonstrates a high rate of
resolution of preexisting diplopia.
PMID- 27608288
TI - Electrostatic spraying in the chemical control of Triozoida limbata (Enderlein)
(Hemiptera: Triozidae) in guava trees (Psidium guajava L.).
AB - BACKGROUND: Owing to the difficulty in reaching targets during pesticide
applications on guava trees, it is important to evaluate new technologies that
may improve pest management. In electrostatic spraying, an electric force is
added to the droplets to control their movements such that they are efficiently
directed to the target. The present study evaluated the performance of
electrostatic and non-electrostatic spraying in the control of the guava psyllid,
the deposition of the spray mixture on the leaves and the losses to the soil.
RESULTS: The deposition of the spray mixture was up to 2 times greater when using
electrostatic spraying in comparison with non-electrostatic application. The
losses of the spray mixture to the soil were up to 4 times smaller with the
electrostatic spraying. Electrostatic spraying had better control of the psyllid.
CONCLUSION: It was possible to reduce the volume rate of application with
electrostatic spraying without adversely affecting the control of the guava
psyllid. (c) 2016 Society of Chemical Industry.
PMID- 27608289
TI - Cell-type-specific modulation of innate immune signalling by vitamin D in human
mononuclear phagocytes.
AB - Vitamin D is widely reported to inhibit innate immune signalling and dendritic
cell (DC) maturation as a potential immunoregulatory mechanism. It is not known
whether vitamin D has global or gene-specific effects on transcriptional
responses downstream of innate immune stimulation, or whether vitamin D
inhibition of innate immune signalling is common to different cells. We confirmed
vitamin D inhibition of nuclear factor-kappaB (NF-kappaB) and p38 mitogen
activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC)
stimulated with lipopolysaccharide (LPS). This was associated with global but
modest attenuation of LPS-induced transcriptional changes at genome-wide level.
Surprisingly, vitamin D did not inhibit innate immune NF-kappaB activation in
monocyte-derived macrophages. Consistent with our findings in MDDC, ex vivo
vitamin D treatment of primary peripheral blood myeloid DC also led to
significant inhibition of LPS-inducible NF-kappaB activation. Unexpectedly, in
the same samples, vitamin D enhanced activation of both NF-kappaB and MAPK
signalling in primary peripheral blood monocytes. In a cross-sectional clinical
cohort, we found no relationship between peripheral blood vitamin D levels and
LPS-inducible activation of NF-kappaB and MAPK pathways in monocytes of myeloid
DC. Remarkably, however, in vivo supplementation of people with vitamin D
deficiency in this clinical cohort also enhanced LPS-inducible MAPK signalling in
peripheral blood monocytes. Therefore, we report that vitamin D differentially
modulates the molecular response to innate immune stimulation in monocytes,
macrophages and dendritic cells. These results are of importance in the design of
studies on vitamin D supplementation in infectious and immunological diseases.
PMID- 27608290
TI - Targeting Phosphatidylserine with a 64Cu-Labeled Peptide for Molecular Imaging of
Apoptosis.
AB - Molecular imaging of programmed cell death (apoptosis) in vivo is an innovative
strategy for early assessment of treatment response and treatment efficacy in
cancer patients. Externalization of phosphatidylserine (PS) to the cell membrane
surface of dying cells makes this phospholipid an attractive molecular target for
the development of apoptosis imaging probes. In this study, we have radiolabeled
PS-binding 14-mer peptide FNFRLKAGAKIRFG (PSBP-6) with positron-emitter copper-64
(64Cu) for PET imaging of apoptosis. Peptide PSBP-6 was conjugated with
radiometal chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through
an aminovaleric acid (Ava) linker for subsequent radiolabeling with 64Cu to
prepare radiotracer 64Cu-NOTA-Ava-PSBP-6. PS-binding potencies of PSBP-6, NOTA
Ava-PSBP-6, and natCu-NOTA-Ava-PSBP-6 were determined in a competitive
radiometric PS-binding assay. Radiotracer 64Cu-NOTA-Ava-PSBP-6 was studied in
camptothecin-induced apoptotic EL4 mouse lymphoma cells and in a murine EL4 tumor
model of apoptosis using dynamic PET imaging. Peptide PSBP-6 was also conjugated
via an Ava linker with fluorescein isothiocyanate (FITC). FITC-Ava-PSBP-6 was
evaluated in flow cytometry and fluorescence confocal microscopy experiments.
Radiopeptide 64Cu-NOTA-Ava-PSBP-6 was synthesized in high radiochemical yields of
>95%. The IC50 values for PS-binding potency of PSBP-6, NOTA-Ava-PSBP-6, and
natCu-NOTA-PSBP-6 were 600 MUM, 30 MUM, and 23 MUM, respectively. A competitive
radiometric cell binding assay confirmed binding of 64Cu-NOTA-Ava-PSBP-6 to
camptothecin-induced apoptotic EL4 cells in a Ca2+-independent manner. PET
imaging studies demonstrated significantly higher uptake of 64Cu-NOTA-Ava-PSBP-6
in apoptotic EL4 tumors (SUV5min 0.95 +/- 0.04) compared to control tumors
(SUV5min 0.74 +/- 0.03). Flow cytometry studies showed significantly higher
binding of FITC-Ava-PSBP-6 to EL4 cells treated with camptothecin compared to
untreated cells. Fluorescence microscopy studies revealed that FITC-Ava-PSBP-6
was binding to cell membranes of early apoptotic cells, but was internalized in
late apoptotic and necrotic cells. The present study showed that radiotracer 64Cu
NOTA-Ava-PSBP-6 holds promise as a first peptide-based PET imaging agent for
molecular imaging of apoptosis. However, additional "fine-tuning" of 64Cu-NOTA
Ava-PSBP-6 is required to enhance PS-binding potency and in vivo stability to
improve tumor uptake and retention.
PMID- 27608291
TI - Perturbation of Akt Signaling, Mitochondrial Potential, and ADP/ATP Ratio in
Acidosis-Challenged Rat Cortical Astrocytes.
AB - Cells switch to anaerobic glycolysis when there is a lack of oxygen during brain
ischemia. Extracellular pH thus drops and such acidosis causes neuronal cell
death. The fate of astrocytes, mechanical, and functional partners of neurons, in
acidosis is less studied. In this report, we investigated the signaling in
acidosis-challenged rat cortical astrocytes and whether these signals were
related to mitochondrial dysfunction and cell death. Exposure to acidic pH (6.8,
6.0) caused Ca2+ release and influx, p38 MAPK activation, and Akt inhibition.
Mitochondrial membrane potential was hyperpolarized after astrocytes were exposed
to acidic pH as soon as 1 h and lasted for 24 h. Such mitochondrial
hyperpolarization was prevented by SC79 (an Akt activator) but not by SB203580 (a
p38 inhibitor) nor by cytosolic Ca2+ chelation by BAPTA, suggesting that only the
perturbation in Akt signaling was causally related to mitochondrial
hyperpolarization. SC79, SB203580, and BAPTA did not prevent acidic pH-induced
cell death. Acidic pH suppressed ROS production, thus ruling out the role of ROS
in cytotoxicity. Interestingly, pH 6.8 caused an increase in ADP/ATP ratio and
apoptosis; pH 6.0 caused a further increase in ADP/ATP ratio and necrosis.
Therefore, astrocyte cell death in acidosis did not result from mitochondrial
potential collapse; in case of acidosis at pH 6.0, necrosis might partly result
from mitochondrial hyperpolarization and subsequent suppressed ATP production. J.
Cell. Biochem. 118: 1108-1117, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27608292
TI - Lesion volume predicts prostate cancer risk and aggressiveness: validation of its
value alone and matched with prostate imaging reporting and data system score.
AB - OBJECTIVE: To demonstrate the association between magnetic resonance imaging
(MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical
significance, evaluating this variable alone and matched with Prostate Imaging
Reporting and Data System version 2 (PI-RADS v2) score. PATIENTS AND METHODS: We
retrospectively analysed 157 consecutive patients, with at least one prior
negative systematic prostatic biopsy, who underwent transperineal prostate
MRI/ultrasonography fusion-targeted biopsy between January 2014 and February
2016. Suspicious lesions were delineated using a 'region of interest' and the
system calculated prostate volume and LV. Patients were divided in groups
considering LV (<=0.5, 0.5-1, >=1 mL) and PI-RADS score (1-5). We considered
clinically significant prostate cancer as all cancers with a Gleason score of >=3
+ 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI
LV) and histological tumour volume (HTV) was done in 23 patients who underwent
radical prostatectomy during the study period. Differences between MRI LV and HTV
were assessed using the paired sample t-test. MRI LV and HTV concordance was
verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal
regression models were used to evaluate difference in frequencies. RESULTS: The
MRI LV and PI-RADS score were associated both with prostate cancer detection
(both P < 0.001) and with significant prostate cancer detection (P < 0.001 and P
= 0.008, respectively). When the two variables were matched, increasing LV
increased the risk within each PI-RADS group. Prostate cancer detection was 1.4
times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of >=1 mL;
significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4
times for LVs of >=1 mL. There was a positive correlation between MRI LV and HTV
(r = 0.9876, P < 0.001). Finally, Bland-Altman analysis showed that MRI LV was
underestimated by 4.2% compared to HTV. Study limitations include its monocentric
and retrospective design and the limited cohort. CONCLUSIONS: This study
demonstrates that PI-RADS score and the MRI LV, independently and in combination,
are associated with prostate cancer detection and with tumour clinical
significance.
PMID- 27608293
TI - Competitive exclusion in a multi-strain immuno-epidemiological influenza model
with environmental transmission.
AB - In this paper, a multi-strain model that links immunological and epidemiological
dynamics across scales is formulated. On the within-host scale, the n strains
eliminate each other with the strain having the largest immunological
reproduction number persisting. However, on the population scale, we extend the
competitive exclusion principle to a multi-strain model of SI-type for the
dynamics of highly pathogenic flu in poultry that incorporates both the infection
age of infectious individuals and biological age of pathogen in the environment.
The two models are linked through the age-since-infection structure of the
epidemiological variables. In addition the between-host transmission rate, the
shedding rate of individuals infected by strain j and the disease-induced death
rate depend on the within-host viral load. The immunological reproduction numbers
[Formula: see text] and the epidemiological reproduction numbers [Formula: see
text] are computed. By constructing a suitable Lyapunov function, the global
stability of the infection-free equilibrium in the system is obtained if all
reproduction numbers are smaller or equal to one. If [Formula: see text], the
reproduction number of strain j is larger than one, then a single-strain
equilibrium, corresponding to strain j exists. This single-strain equilibrium is
globally stable whenever [Formula: see text] and [Formula: see text] is the
unique maximal reproduction number and all of the reproduction numbers are
distinct. That is, the strain with the maximal basic reproduction number
competitively excludes all other strains.
PMID- 27608295
TI - Metabolomic profiling of brain from infants who died from Sudden Infant Death
Syndrome reveals novel predictive biomarkers.
AB - OBJECTIVE: Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of
an infant <1 year of age that cannot be explained following a thorough
investigation. Currently, no reliable clinical biomarkers are available for the
prediction of infants who will die of SIDS. STUDY DESIGN: This study aimed to
profile the medulla oblongata from postmortem human brain from SIDS victims
(n=16) and compare their profiles with that of age-matched controls (n=7).
RESULTS: Using LC-Orbitrap-MS, we detected 12 710 features in electrospray
ionization positive (ESI+) mode and 8243 in ESI- mode from polar extracts of
brain. Five features acquired in ESI+ mode produced a predictive model for SIDS
with an area under the receiver operating characteristic curve (AUC) of 1
(confidence interval (CI): 0.995-1) and a predictive power of 97.4%. Three
biomarkers acquired in ESI- mode produced a predictive model with an AUC of 0.866
(CI: 0.767-0.942) and a predictive power of 77.6%. We confidently identified 5 of
these features (l-(+)-ergothioneine, nicotinic acid, succinic acid, adenosine
monophosphate and azelaic acid) and putatively identify another 4 out of the 15
in total. CONCLUSIONS: This study underscores the potential value of metabolomics
for studying SIDS. Further characterization of the metabolome of postmortem SIDS
brains could lead to the identification of potential antemortem biomarkers for
novel prevention strategies for SIDS.
PMID- 27608296
TI - Gestational weight gain and preterm birth: disparities in adolescent pregnancies.
AB - OBJECTIVE: To examine racial differences in the association between gestational
weight gain and preterm birth subtypes among adolescents. STUDY DESIGN: We
conducted a retrospective cohort study of 211 403 adolescents using 2012 United
States natality data. The outcome was preterm birth and the primary exposure was
gestational weight gain. Multinomial logistic regression analyses were used to
estimate adjusted odds ratios, stratified by race and body mass index (BMI).
RESULTS: Black and White mothers who gained below the recommendations had
increased risks for spontaneous preterm birth in all BMI categories, except
obese. All Hispanic mothers who gained below the recommendations had increased
risks of spontaneous preterm birth. White normal and overweight mothers and
Black, Hispanic and Other normal weight mothers who exceeded the recommendations
had decreased risks of spontaneous preterm birth. CONCLUSION: The effect of
gestational weight gain on spontaneous and medically indicated preterm birth is
modified by race and BMI.
PMID- 27608297
TI - Projected shifts in fish species dominance in Wisconsin lakes under climate
change.
AB - Temperate lakes may contain both coolwater fish species such as walleye (Sander
vitreus) and warmwater fish species such as largemouth bass (Micropterus
salmoides). Recent declining walleye and increasing largemouth bass populations
have raised questions regarding the future trajectories and management actions
for these species. We developed a thermodynamic model of water temperatures
driven by downscaled climate data and lake-specific characteristics to estimate
daily water temperature profiles for 2148 lakes in Wisconsin, US, under
contemporary (1989-2014) and future (2040-2064 and 2065-2089) conditions. We
correlated contemporary walleye recruitment and largemouth bass relative
abundance to modeled water temperature, lake morphometry, and lake productivity,
and projected lake-specific changes in each species under future climate
conditions. Walleye recruitment success was negatively related and largemouth
bass abundance was positively related to water temperature degree days. Both
species exhibited a threshold response at the same degree day value, albeit in
opposite directions. Degree days were predicted to increase in the future,
although the magnitude of increase varied among lakes, time periods, and global
circulation models (GCMs). Under future conditions, we predicted a loss of
walleye recruitment in 33-75% of lakes where recruitment is currently supported
and a 27-60% increase in the number of lakes suitable for high largemouth bass
abundance. The percentage of lakes capable of supporting abundant largemouth bass
but failed walleye recruitment was predicted to increase from 58% in contemporary
conditions to 86% by mid-century and to 91% of lakes by late century, based on
median projections across GCMs. Conversely, the percentage of lakes with
successful walleye recruitment and low largemouth bass abundance was predicted to
decline from 9% of lakes in contemporary conditions to only 1% of lakes in both
future periods. Importantly, we identify up to 85 resilient lakes predicted to
continue to support natural walleye recruitment. Management resources could
target preserving these resilient walleye populations.
PMID- 27608298
TI - Site-Specific Isotope-Labeling of Inosine Phosphoramidites and NMR Analysis of an
Inosine-Containing RNA Duplex.
AB - Structural features and internal dynamics of inosine-containing RNAs are poorly
understood. NMR studies of such RNAs require 13 C,15 N-labeling, which cannot be
achieved using in vitro transcription as inosine and guanosine are not
distinguished by RNA polymerase. Herein, we report the synthesis of an inosine
phosphoramidite with selective 13 C8 and 15 N7-isotope incorporation in the base
and uniform 13 C-labeling of the ribose. Chemical synthesis of an RNA duplex
containing four consecutive IU base pairs with this optimized isotope-labeling
scheme greatly simplifies NMR spectra and resolves signal overlap. The absence of
detectable NMR signals of imino protons and unusual inter-residue NOE
correlations in this RNA indicate deviations from standard A-form geometry,
consistent with reduced stability of this duplex seen in UV melting studies
compared to its nonedited RNA counterparts. These studies indicate that the
introduction of IU base pairs distorts and destabilizes RNA helices significantly
compared to the also noncanonical GU base-pairs. Our optimized isotope-labeling
scheme enables high-resolution NMR studies of inosine-edited RNAs.
PMID- 27608300
TI - Cautionary Tales of Inapproximability.
AB - Modeling biology as classical problems in computer science allows researchers to
leverage the wealth of theoretical advancements in this field. Despite countless
studies presenting heuristics that report improvement on specific benchmarking
data, there has been comparatively little focus on exploring the theoretical
bounds on the performance of practical (polynomial-time) algorithms. Conversely,
theoretical studies tend to overstate the generalizability of their conclusions
to physical biological processes. In this article we provide a fresh perspective
on the concepts of NP-hardness and inapproximability in the computational biology
domain, using popular sequence assembly and alignment (mapping) algorithms as
illustrative examples. These algorithms exemplify how computer science theory can
both (a) lead to substantial improvement in practical performance and (b)
highlight areas ripe for future innovation. Importantly, we discuss caveats that
seemingly allow the performance of heuristics to exceed their provable bounds.
PMID- 27608299
TI - The tyrosine kinase inhibitor tyrphostin AG126 reduces activation of inflammatory
cells and increases Foxp3+ regulatory T cells during pathogenesis of rheumatoid
arthritis.
AB - Protein tyrosine kinases are key mediators of the signal transduction cascades
that control expression of many genes involved in the induction of inflammation
caused by arthritis. Here we investigate the effect of the tyrosine kinase
inhibitor tyrphostin AG126 on a mouse model of adjuvant-induced arthritis (AIA).
We report that when given at 5mg/kg i.p. every 48h from days 0-21, AG126 exerts
potent anti-arthritic effects. Further, we investigated the role of AG126 on the
key mediators of arthritic inflammation, namely, edema, arthritic score, presence
of immunophenotypes including Foxp3+, CD4+Foxp3+, and CD25+Foxp3+ T regulatory
(Treg) cells, as well as pro- and anti-inflammatory mediators. AG126 treatment
significantly attenuated the severity of AIA and caused a substantial reduction
in the percentage of CD2+, CD3+, CD4+, CD8+, CD23+, CD80+, CD86+ CD122+, CD195+,
TCRbeta+, and GITR+ cells in whole blood. Moreover, administration of AG126 under
arthritis-inducing conditions resulted in suppression of IL-17A+, IFN-gamma+,
CD4+ and CD25+ populations while causing an increase in the Foxp3+, CD4+Foxp3+,
and CD25+Foxp3+ Treg populations in the spleen. In addition, RT-PCR analysis
revealed increased expression of CD4, CD8, IL-17A, IFN-gamma, TNF-alpha, and NF
kappaB p65 mRNAs and decreased IL-4 mRNA in the arthritic control (AC) mice,
while treatment of animals with AG126 reversed these effects. Western blot
analysis confirmed the decreased expression of IL-17, GITR, NF-kappaB p65
proteins and increased Foxp3 and IL-4 proteins following AG126 treatment of knee
tissue. Thus, our findings provide new evidence that inhibition of protein
tyrosine kinase activity decreases the progression of arthritis.
PMID- 27608301
TI - Behavioral self-management strategies for practice and exercise should be
included in neurologic rehabilitation trials and care.
AB - PURPOSE OF REVIEW: Rehabilitation trials and postacute care to lessen impairments
and disability after stroke, spinal cord injury, and traumatic brain injury
almost never include training to promote long-term self-management of skills
practice, strengthening and fitness. Without behavioral training to develop self
efficacy, clinical trials, and home-based therapy may fail to show robust
results. RECENT FINDINGS: Behavioral theories about self-management and self
efficacy for physical activity have been successfully incorporated into
interventions for chronic diseases, but rarely for neurologic rehabilitation. The
elements of behavioral training include education about the effects of practice
and exercise that are relevant to the person, goal setting, identification of
possible barriers, problem solving, feedback about performance, tailored
instruction, decision making, and ongoing personal or social support. Mobile
health and telerehabilitation technologies offer new ways to remotely enable such
training by monitoring activity from wearable wireless sensors and instrumented
exercise devices to allow real-world feedback, goal setting, and instruction.
SUMMARY: Motivation, sense of responsibility, and confidence to practice and
exercise in the home can be trained to increase adherence to skills practice and
exercise both during and after formal rehabilitation. To optimize motor learning
and improve long-term outcomes, self-management training should be an explicit
component of rehabilitation care and clinical trials.
PMID- 27608302
TI - In vivo and in vitro inhibitory activity of an ethanolic extract of Sargassum
fulvellum and its component grasshopper ketone on atopic dermatitis.
AB - The present study investigated the effect of Sargassum fulvellum ethanol extract
(SFEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like
skin lesions in BALB/c mice. The severity of skin dermatitis, production of
cytokines, and total IgE content were measured, and the histopathological
features were analyzed. SFEE decreased the severity of DNCB-induced dermatitis
and suppressed the serum levels of total immunoglobulin E (IgE), tumor necrosis
factor (TNF)-alpha, and interleukin (IL)-4. In addition, SFEE reduced the
production of IL-4, IL-5, and IL-13 in mice splenocytes. However, the levels of
IL-10 and interferon (IFN)-gamma significantly increased in mice sera and
splenocytes. Histological examination revealed decreased dermal thickness and
infiltration by mast cells after treatment with SFEE. Furthermore, grasshopper
ketone, a compound isolated from SFEE, was found to significantly decrease
cytokine production in concanavalin A-stimulated splenocytes from BALB/c mice
with no cytotoxicity. Taken together, these results indicate that SFEE and the
isolated grasshopper ketone have an inhibitory effect on AD by regulating immune
mediators and cells and may be a potential effective alternative therapy for AD.
PMID- 27608303
TI - Tumor-associated macrophages promote invasion via Toll-like receptors signaling
in patients with ovarian cancer.
AB - Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes
recruit into tumor microenvironment and display functions associated with tumor
progression. The mechanisms by which TAMs display roles that associated with the
invasion ability of ovarian cancer have not been well investigated. In our
research, we found abundant TAMs infiltrate in ovarian cancer compared with
benign ovarian tumor tissues. Levels of matrix metalloproteinase (MMP)-2, MMP-9
and MMP-10, and Toll-like receptors (TLRs) signaling proteins were evaluated in
ovarian cancer. The high level of TAMs was associated with metastasis and advance
of patients with ovarian cancer. TAMs and ovarian cancer cell line SKOV3 were
cocultured in vitro, MMPs level and the invasion ability of SKOV3 cells were
significantly up-regulated. The coculture process was correlated with the
activation of TLRs signaling and downstream nuclear factor (NF)-kappaB p65 and
microtubule-associated proteins (MAPs) kinases pathway in SKOV3. In addition, pre
incubation with TLRs signaling inhibitors remarkably suppressed invasion ability
of SKOV3. Levels of TLRs signaling pathways proteins were also down-regulated in
this blocking process. These findings demonstrated that TAMs promoted up
regulation of MMP-2, MMP-9 and MMP-10 expressions and enhanced ovarian cancer
cells invasion via TLRs signaling pathway. We conclude that TAMs could enhance
ovarian cancer cells invasion and ultimately promote ovarian cancer progression.
PMID- 27608304
TI - [Update in Infectious Diseases 2016].
AB - Antimicrobial resistance increases it health, social and economic impact. in all
areas (state, regional and local), initiatives to try to contain the problem of
resistance arise. In the update of this year 2016, we study microbiological,
epidemiological and clinical aspects of multi-resistant bacteria, as well as
resources for therapeutic approach, from ancient to modern drugs from therapeutic
combinations to optimization Stewardship programs. In the case of fungal
infection, we analyze clinical scenarios with different species in yeast or new
clinical settings in filamentous fungi. Taking paediatric population, homologies
and differences with adults in invasive fungal infection were compared. Finally
in the field of parasitology, treatment of severe malaria imported or that
resistant to antimalarial drugs were reviewed.
PMID- 27608305
TI - [Epidemiology of the infection by resistant Gram-positive microorganisms].
AB - Resistance among Gram-positive microorganisms to classical and new antimicrobials
is a therapeutic threat. In Spain, methicillin resistance among Staphylococcus
aureus (25-30%) and coagulase-negative staphylococci (50-60%) seems to have
stabilized in the last decade. Among enterococci, vancomycin resistance is less
than 5%. Both linezolid and daptomycin, in general, show good activity against
these microorganisms. However, the resistance rates of Staphylococcus epidermidis
to linezolid (20.9%), and of Enterococcus faecium to daptomycin (10.5%) in
isolates from intensive care units are a worrying.
PMID- 27608306
TI - [Empirical therapeutic approach to infection by resistant gram positive (acute
bacterial skin and skin structure infections and health care pneumonia). Value of
risk factors].
AB - Antibiotic treatment inadequacy is common in these sites of infection and may
have implications for the patient's prognosis. In acute bacterial skin and skin
structure infections, the document states that for the establishment of an
adequate treatment it must be assessed the severity, the patient comorbidity and
the risk factors for multidrug-resistant microorganism. The concept of health
care-associated pneumonia is discussed and leads to errors in the etiologic
diagnosis and therefore in the selection of antibiotic treatment. This paper
discusses how to perform this approach to the possible etiology to guide
empirical treatment.
PMID- 27608307
TI - [Directed therapeutic approach to Staphylococcus aureus infections. Clinical
aspects of prescription].
AB - Infections caused by Staphylococcus aureus have had classically an important
impact in morbidity and mortality in the nosocomial and community scene. The
description of methicillin resistance among nosocomial isolates of S. aureus and
his widespread diffusion has become methicillin-resistant S. aureus (MRSA) in one
of the most common causes of bacterial nosocomial infections. In the last years
MRSA strains have also emergence in the community. This together with a
progressive increase in resistance to antibiotics used classically has become
vancomycin in the treatment of choice in most cases according to clinical
guidelines. As a result, a progressive rise in the minimum inhibitory
concentration (MIC) to vancomycin has been reported. In this context strains with
intermediate susceptibility to vancomycin (MIC 8-4 mg/L) and heteroresistance
have been noted. These strains are associated with a higher risk of treatment
failure when using vancomycin. Among isolates of S. aureus susceptible to
vancomycin there has been described stains with elevated MICs (>=1.5 mg/L). It is
controversial if the presence of these strains has an impact on clinical outcome
if treatment with vancomycin or beta-lactams is prescribed. The development of
new antibiotics with activity against MRSA and exploring synergies offer a
promising alternative to treatment with vancomycin.
PMID- 27608308
TI - [Epidemiology of multi-drug resistant gramnegative bacilli].
AB - Current antimicrobial resistance in Gram negative bacilli is particularly
worrisome due to development of resistance to all available antimicrobial agents.
This situation dramatically limits therapeutic options. The microorganisms
acquire a multiresistance phenotype as a consequence of different complex
processes in which the antimicrobials acts as selective driver of resistance.
Dissemination of multiresistant bacteria is driven by the expansion of the high
risk clones. These clones can be selected in the presence of antimicrobials
allowing their persistence over time.
PMID- 27608309
TI - [Resistant gram-negative bacteria. Therapeutic approach and risk factors].
AB - The rapid spread of multidrug-resistant bacteria has become a serious threat,
especially in critical care units, thereby prolonging the hospital stay.
Enterobacteriaceae have a high capacity to adapt to any environment. Plasmids are
the reason behind their expansion. The choice of empiric therapy for intra
abdominal or urinary infections requires knowledge of the intrinsic
microbiological variability of each hospital or critical care unit, as well as
the source of infection, safety or antibiotic toxicity, interaction with other
drugs, the dosage regimen and the presence of risk factors. Carbapenems are the
drug of choice in the case of suspected infection by ESBL-producing
Enterobacteriaceae. The new ceftazidime/avibactam and ceftolozane/tazobactam
drugs are opening up promising new horizons in the treatment of multidrug
resistant Enterobacteriaceae.
PMID- 27608310
TI - [Approach to directed therapy after knowledge of the isolate: carbapenemase
producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa and
carbapenem-resistant Acinetobacter baumannii].
AB - Directed treatment of infections due to multidrug-resistant Gram-negative bacilli
is a difficult task, since it requires the use of a limited number of antibiotics
that are often more toxic and possibly less efficacious than beta-lactams and
fluoroquinolones. Furthermore, there are very few controlled trials informing on
the relative efficacy of different therapeutic strategies. As a general rule, it
is recommended to use at least two active drugs or a combination with proven
synergistic activity in vitro, because several observational studies have
associated this practice with better outcomes and as a measure to potentially
curb the emergence of further resistance. It is already available a new
cephalosporin active against most strains of Pseudomonas aeruginosa resistant to
ceftazidime due to derepression of ampC and in the near future an effective
inhibitor of class A, class C and OXA-48 will be available which combined with
ceftazidime is expected to mean a significant addition to the armamentarium
against Gram-negative bacilli with these resistance determinants.
PMID- 27608311
TI - [Multidrug-resistant tuberculosis: current epidemiology, therapeutic regimens,
new drugs].
AB - Multidrug and extensively resistant tuberculosis are especially severe forms of
the disease for which no efficacious therapy exists in many cases. All the
countries in the world have registered cases, although most of them are diagnosed
in resource-limited countries from Asia, Africa and South America. For adequate
treatment, first- and second-line antituberculosis drugs have to be judiciously
used, but the development of new drugs with full activity, good tolerability and
little toxicity is urgently needed. There are some drugs in development, some of
which are already available through expanded-access programs.
PMID- 27608312
TI - [Old and new antibiotics for therapy of multidrug resistant bacteria].
AB - The lack of new antibiotics for multidrug-resistant bacteria is a matter of
concern in microorganisms such as Pseudomonas aeruginosa, ESBL- and carbapenemase
producing Enterobacteriaceae, Acinetobacter baumannii, methicillin-resistant
Staphylococcous aureus and vancomycin-resistant Enterococcus faecium. This
situation has conditioned the reuse of "old" antibiotics (colistin, fosfomycin),
the use of more recent antibiotics with new indications or dosage regimens
(tigecycline, meropenem) and the introduction of "new" antibiotics (beta-lactams,
lipoglycopeptides, oxazolidinones) that are the subject of this review.
PMID- 27608313
TI - [Monotherapy vs. combined therapy in the treatment of multi-drug resistance
gramnegative bacteria].
AB - The increasing number of multidrug resistant gram negative bacteria, particularly
in patients with risk factors, but in those who suffer community infections as
well, is doing more and more difficult to choose the appropriate treatment. The
most challenging cases are due to the production of extended-spectrum-beta
lactamases (ESBL) and carbapenemases. This mini-review will discuss the adequacy
of administering carbapenems when suspecting infections due to ESBL that could be
modified after knowing the MIC of the isolated bacteria and the combined therapy
in cases of carbapenemases, being particularly important to include a carbapenem
and/or colistine at high dosages in this combination.
PMID- 27608314
TI - [The role of antimicrobial stewardship programs in the control of bacterial
resistance].
AB - In order to improve infection prognosis and reduce the existing microbial
resistance problem (a challenge similar to that of climate change), a higher
implication of the Administration, an increased level of social awareness and the
development of specific corporate networks, including the pharmaceutical
industry, is needed. However, we must first consolidate Antimicrobial Stewardship
Programmes with experts who seek to improve antibiotic therapy effectivity in
severe infections and to reduce global antibiotic exposure.
PMID- 27608315
TI - [Diagnostic and therapeutic approach of intraabdominal candidiasis].
AB - Invasive fungal disease is associated to a high mortality rate on critical ill
patients. In the last decades an important epidemiological shift has been
described. Early diagnosis and treatment are related with a better prognosis. The
key factors lie in a set of predictive scores that allow to identify patients
that will benefit of early treatment, as well as using diagnosis techniques that
are culture independent. New diagnosis approximations are being developed with
promising results: in situ hybridisation using PNA-FISH probes, MALDI-TOF MS and
rapid nucleic acids detection assays. The use of echinocandin is recommended as
antifungal therapy on critical ill patients with candida peritonitis.
PMID- 27608316
TI - [Invasive pulmonary aspergillosis in non-neutropenic patients].
AB - The incidence of invasive pulmonary aspergillosis (IPA) is increasing among non
neutropenic patients in recent years. The difficulty of early diagnosis in these
patients involves a delay in the onset of adequate treatment and higher
mortality.
PMID- 27608317
TI - [Invasive fungal infections in children: similarities and differences with
adults].
AB - Invasive fungal infections (IFI) are a major cause of morbidity and mortality in
immunocompromised adults and children. The purpose of this review was to update
the epidemiological, clinical and therapeutic options in children, and to compare
them with the adult population. Although there are important differences, the
epidemiology, clinical features and risk factors for IFI have many similarities.
Patient at risk include neutropenic hematology children, in whom Candida spp. y
Aspergillus spp. predominate; primary immunodeficiencies, particularly chronic
granulomatous disease with high susceptibility for Aspergillus spp.; and
extremely premature infants, in whom C. albicans y C. parapsilosis are more
prevalent. Premature babies are prone to dissemination, including the central
nervous system. There are peculiarities in radiology and diagnostic biomarkers in
children. In pulmonary aspergillosis, clasical signs in CT are usually absent.
There is scant information on PCR and beta-D-glucan in children, and more limited
on the performance of galactomannan enzyme immunoassay, that does not appear to
be much different in neutropenic patients. There is a delay in the development of
antifungals, limiting their use in children. Most azoles require therapeutic drug
monitoring in children to optimize its safety and effectiveness. Pediatric
treatment recommendations are mainly extrapolated from results of clinical trials
performed in adults. There is no evidence for the benefit of preemptive therapy
in children. It is necessary to foster specific pediatric studies with current
and new antifungals to evaluate their pharmacokinetics, safety, and effectiveness
at different ages in the pediatric population.
PMID- 27608318
TI - [Current management of imported severe malaria].
AB - Severe malaria is a diagnostic and therapeutic emergency with great impact
worldwide for incidence and mortality. The clinical presentation of severe
malaria can be very polymorphic and rapidly progressing. Therefore a correct
diagnosis and an early and adequate antiparasitic and support therapy are
essential. This paper attempts to outline the diagnosis frame and the treatment
of severe malaria for adults, paediatric patients and for pregnant.
PMID- 27608319
TI - [Resistance to the antimalarial drugs].
AB - Malaria is one of the most widespread infectious diseases around the world with
214 million cases and 438,000 deaths in 2015. In the early twentieth century it
was described for the first time the resistance to quinine and, since then, drug
resistance to antimalarial drugs has spread up to represent a global challenge in
the fight and control of malaria. Understanding the mechanisms, geography and
monitoring tools that we can act against resistance to antimalarial drugs is
critical to prevent its expansion.
PMID- 27608320
TI - Can we use plasma hyperosmolality as a predictor of mortality for ST-segment
elevation myocardial infarction?
AB - BACKGROUND: The aim of this study was to investigate the association of plasma
osmolality with all-cause mortality in ST-segment elevation myocardial infarction
(STEMI) patients treated with a primary percutaneous coronary intervention.
METHODS: This study included 3748 patients (mean age 58.3+/-11.8 years, men 81%)
with STEMI treated with primary percutaneous coronary intervention. The following
formula was used to measure the plasma osmolality at admission:
osmolality=1.86*sodium (mmol/l)+glucose (mg/dl)/18+BUN (mg/dl)/2.8+9. RESULTS:
The patients were followed up for a mean period of 22+/-10 months. Patients with
higher plasma osmolality had 3.7 times higher in-hospital (95% confidence
interval: 2.7-5.1) and 3.2 times higher long-term (95% confidence interval: 2.5
4.1) all-cause mortality rates than patients with lower plasma osmolality.
CONCLUSION: Plasma osmolality was found to be a predictor of both in-hospital and
long-term all-cause mortality. Hence, plasma osmolality can be used to detect
high-risk patients in STEMI.
PMID- 27608321
TI - Spontaneous coronary artery dissection with intra-adventitial hematoma detected
by high-definition intravascular ultrasound.
PMID- 27608322
TI - Tobacco consumption and spontaneous quitting at the first trimester of pregnancy.
AB - INTRODUCTION: The purpose of this study was to examine the association between
pregnant women's socio-demographic characteristics, smoking-related variables and
psychological symptoms (anxiety and depression) and both tobacco consumption and
spontaneous quitting at the first trimester of pregnancy. In particular, we
wished to examine the contribution of depressive symptoms to tobacco consumption
and spontaneous quitting, while controlling for anxiety symptoms, socio
demographic and smoking-related variables. METHODS: The sample was comprised of
901 Spanish pregnant women. Assessment included an ad hoc questionnaire with
socio-demographic and tobacco consumption information, the Edinburg Postnatal
Depression Scale (EPDS), and The State-Anxiety Inventory (STAI-S). Two multiple
logistic regression analyses were performed, respectively to predict tobacco
consumption and to predict spontaneous quitting. RESULTS: Having a partner who
smokes (OR=5.578), not having a college education (OR=2.803), higher scores on
the EPDS (OR=1.073) and higher scores on the STAI-S (OR=1.027) increase the
probability of continuing smoking. Being primiparous (OR=2.463), having a college
education (OR=2.141), smoking fewer cigarettes before pregnancy (OR=1.175), and
lower scores on the STAI-S (OR=1.045) increase the probability of spontaneously
quitting smoking at the first trimester of pregnancy. CONCLUSIONS: Depressive
symptoms were a predictor of tobacco consumption but not of spontaneous quitting;
spontaneous quitting was better predicted by anxiety symptoms. These findings
support recommendations that women with depressive symptoms are at risk for
smoking during pregnancy and highlight that anxious symptoms should be targeted
in interventions for smoking cessation during pregnancy.
PMID- 27608323
TI - Desire thinking as a predictor of craving and binge drinking: A longitudinal
study.
AB - Desire thinking is a conscious and voluntary cognitive process orienting to
prefigure images, information and memories about positive target-related
experience. Desire thinking has been found to be associated with both craving and
alcohol use in clinical and non-clinical populations, however its role in
predicting craving and problematic drinking patterns has never been investigated
using a longitudinal design. The central aim of the present study was to explore
the role of desire thinking at Time 2 (3months post-baseline) in predicting
craving and binge drinking and Time 3 (6months post-baseline), controlling for
levels of both these constructs and Time 1 (baseline). One hundred and thirty
three non-hazardous drinkers were assessed on craving and binge drinking at Times
1 and 3, and on desire thinking at Time 2. Findings showed that desire thinking
at Time 2 predicted craving and binge drinking at Time 3, controlling for craving
and binge drinking at Time 1. Furthermore, the imaginal prefiguration component
of desire thinking at Time 2 was found to mediate the relationship between
craving at Times 1 and 3; conversely the verbal perseveration component of desire
thinking at Time 2 was found to mediate the relationship between binge drinking
at Times 1 and 3. The implications of these findings are discussed.
PMID- 27608324
TI - The relationship of waterpipe use with cigarette smoking susceptibility and
nicotine dependence: A cross-sectional study among Hong Kong adolescents.
AB - INTRODUCTION: Waterpipe smoking has become increasingly popular in adolescents.
We examined the association of waterpipe smoking with cigarette smoking
susceptibility and nicotine dependence among adolescents in Hong Kong. METHODS:
We analyzed the data of School-based Survey on Smoking among Students 2012/13
from a representative sample of 45,857 secondary school students (US grades 7-12)
in Hong Kong. Among never cigarette smokers (n=37,740), we conducted chi-square
test to compare cigarette smoking susceptibility by current (past 30-day)
waterpipe smoking status, and used multivariate logistic regression to examine
the association between current waterpipe smoking and cigarette smoking
susceptibility controlling for age, sex, peer cigarette smoking, and living with
a cigarette smoker. Then we conducted chi-square test and multivariate logistic
regression among current cigarette smokers (n=1694) to examine the relationship
of current waterpipe smoking with two nicotine dependence outcomes, including
heavier smoking (>=5 cigarettes/day) and first cigarette within 30min of waking,
controlling for demographics and the number of smoking days in the past 30days.
RESULTS: Among never cigarette smokers, current waterpipe use was associated with
cigarette smoking susceptibility (adjusted odds ratio [AOR]=3.58, 95% confidence
interval [CI]: 1.61-7.97). Of current cigarette smokers, waterpipe use was
associated with heavier smoking (AOR=1.56, 95% CI: 1.00-2.43) and first cigarette
within 30min of waking (AOR=2.08, 95% CI: 1.35-3.19). CONCLUSIONS: Surveillance,
prevention, and intervention programs should address waterpipe use in addition to
cigarette smoking. Educational programs need to inform youth about the harmful
and addictive effects of waterpipe smoking. Public health campaigns
deglamourizing waterpipe use may help reduce waterpipe smoking among youth.
PMID- 27608326
TI - Transport on Active Paramagnetic Colloidal Networks.
AB - We dynamically self-assemble an active paramagnetic colloidal network that
ballistically transports nonmagnetic fluorescent colloidal particles on top of
the network. The transport mechanism is put into effect by a directed
hydrodynamic flow, created by the rotation of individual colloids forming the
network. The ballistic transport is confined to the network, and tracer beads in
meshes show a diffusive instead of a ballistic transport. We develop a simple
model to explain the transport.
PMID- 27608325
TI - Genetic diversity and demographic history of the giant river catfish Sperata
seenghala inferred from mitochondrial DNA markers.
AB - The giant river catfish Sperata seenghala has huge demand in South Asian
countries due to its low number of intramuscular bones and nutritive value.
However, the culture practises for this fish have not been standardized and the
current demand for this fish is being met by capture fisheries only. Unregulated
and indiscriminate fishing would lead overexploitation of fish stocks
subsequently stock depletion. Genetic diversity between populations would give
insight about population structure and demography. In the present study, S.
seenghala stocks from three rivers, namely Ganga, Brahmaputra and Mahanadi were
characterized using cytochrome b gene and D-loop region. Moderate to high
haplotype diversity and low nucleotide diversity values were observed in all
populations. Analysis of molecular variance and pairwise FST values showed
significant genetic differentiation among populations. Patterns of diversity,
haplotype networks and mismatch distribution strongly suggest a historical
influence on the genetic structure of S. seenghala populations. S. seenghala
stocks from these three rivers are genetically distinct units and management
measures should be formulated separately for each population.
PMID- 27608327
TI - Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy.
AB - Radiotherapy is one of the most commonly used cancer treatments, with an estimate
of 40% success that could be improved further if more efficient targeting and
retention of radiation at the tumor site were achieved. This review focuses on
the use of dendrimers in radionanotherapy, an emerging technology aimed to
improve the efficiency of radiotherapy by implementing nanovectorization, an
already established praxis in drug delivery and diagnosis. The labeling of
dendrimers with radionuclides also aims to reduce the dose of radiolabeled
materials and, hence, their toxicity and tumor resistance. Examples of
radiolabeled dendrimers with alpha, beta, and Auger electron emitters are
commented, along with the use of dendrimers in boron neutron capture therapy
(BNCT). The conjugation of radiolabeled dendrimers to monoclonal antibodies for a
more efficient targeting and the application of dendrimers in gene delivery
radiotherapy are also covered.
PMID- 27608328
TI - Hidradenitis suppurativa is not associated with the metabolic syndrome based on
body type: A cross-sectional study.
AB - A body type with a high waist circumference or elevated waist-to-hip ratio (WHR),
known as the "apple" body type, represents central/visceral obesity and is
associated with the metabolic syndrome. The aim of this study was to
simultaneously investigate the body mass index (BMI) and WHR in order to classify
body types in individuals with hidradenitis suppurativa (HS) compared with a
general dermatological population. A hospital-based cross-sectional study was
performed in the Netherlands. One hundred and six HS patients and 212 controls
were included. The BMI was significantly higher in the HS group in comparison
with the control group, at 27.8 +/- 5.4 and 25.6 +/- 4.8, respectively (P <
0.001). The WHR did not significantly differ between HS patients and the control
dermatological population (P > 0.05). A more peripheral pattern of bodyweight
distribution was seen in 43% of the 37 obese HS individuals, in contrast to 19%
of 31 obese patients in the control group (P = 0.036). In conclusion, the body
type in obese HS patients, based on the WHR, shows a more peripheral pattern and
differs from the WHR in the BMI-matched general dermatological population.
PMID- 27608329
TI - Oxocarbon Salts for Fast Rechargeable Batteries.
AB - Oxocarbon salts (M2 (CO)n ) prepared through one-pot proton exchange reactions
with different metal ions (M=Li, Na, K) and frameworks (n=4, 5, 6) have been
rationally designed and used as electrodes in rechargeable Li, Na, and K-ion
batteries. The results show that M2 (CO)5 /M2 (CO)6 salts can insert two or four
metal ions reversibly, while M2 (CO)4 shows less electrochemical activity.
Especially, we discover that the K2 C6 O6 electrode enables ultrafast potassium
ion insertion/extraction with 212 mA h g(-1) at 0.2 C and 164 mA h g(-1) at 10 C.
This behavior can be ascribed to the natural semiconductor property of K2 C6 O6
with a narrow band gap close to 0.9 eV, the high ionic conductivity of the K-ion
electrolyte, and the facilitated K-ion diffusion process. Moreover, a first
example of a K-ion battery with a rocking-chair reaction mechanism of K2 C6 O6 as
cathode and K4 C6 O6 as anode is introduced, displaying an operation voltage of
1.1 V and an energy density of 35 Wh kg(-1) . This work provides an interesting
strategy for constructing rapid K-ion batteries with renewable and abundant
potassium materials.
PMID- 27608330
TI - A Young Man With Enlarging Unilateral Tonsil Mass.
PMID- 27608333
TI - Professor Michael Paech-Editor of Anaesthesia and Intensive Care: 2007 to 2016.
PMID- 27608332
TI - Early Resuscitators.
PMID- 27608331
TI - Antagonistic Effects of Endogenous Nitric Oxide in a Glioblastoma Photodynamic
Therapy Model.
AB - Gliomas are aggressive brain tumors that are resistant to conventional
chemotherapy and radiotherapy. Much of this resistance is attributed to
endogenous nitric oxide (NO). Recent studies revealed that 5-aminolevulinic acid
(ALA)-based photodynamic therapy (PDT) has advantages over conventional
treatments for glioblastoma. In this study, we used an in vitro model to assess
whether NO from glioblastoma cells can interfere with ALA-PDT. Human U87 and U251
cells expressed significant basal levels of neuronal NO synthase (nNOS) and its
inducible counterpart (iNOS). After an ALA/light challenge, iNOS level increased
three- to fourfold over 24 h, whereas nNOS remained unchanged. Elevated iNOS
resulted in a large increase in intracellular NO. Extent of ALA/light-induced
apoptosis increased substantially when an iNOS inhibitor or NO scavenger was
present, implying that iNOS/NO was acting cytoprotectively. Moreover, cells
surviving a photochallenge exhibited a striking increase in proliferation,
migration and invasion rates, iNOS/NO again playing a dominant role. Also
observed was a large iNOS/NO-dependent increase in matrix metalloproteinase-9
activity, decrease in tissue inhibitor of metalloproteinase-1 expression and
increase in survivin and S100A4 expression, each effect being consistent with
accelerated migration/invasion as a prelude to metastasis. Our findings suggest
introduction of iNOS inhibitors as pharmacologic adjuvants for glioblastoma PDT.
PMID- 27608334
TI - Cytomegalovirus reactivation in the critically ill septic intensive care patient:
pathogen or passenger?
PMID- 27608335
TI - Anaesthetic implications of mild cognitive impairment.
PMID- 27608336
TI - Speckle tracking echocardiography in the critically ill: enticing research with
minimal clinical practicality or the answer to non-invasive cardiac assessment?
AB - Echocardiography is developing rapidly. Speckle tracking echocardiography is the
latest semi-automatic tool that has potential to quantitatively describe cardiac
dysfunction that may be unrecognised by conventional echocardiography. It is a
non-Doppler, angle-independent, feasible and reproducible method to evaluate
myocardial function in both non-critically ill and critically ill populations.
Increasingly it has become a standard measure of both left and right ventricle
function in specific patient groups, e.g. chemotherapy-induced cardiomyopathy or
pulmonary hypertension. To date there are few studies in the critically ill,
predominantly in sepsis, yet all describe dysfunction beyond standard measures.
Other areas of interest include heart-lung interactions, right ventricle function
and twist and torsion of the heart. A word of caution is required, however, in
that speckle tracking echocardiography is far from perfect and is more
challenging, particularly in the critically ill, than implied by many published
studies. It takes time to learn and perform and most values are not validated,
particularly in the critically ill. We should be cautious in accepting that the
latest software used in cardiology cohorts will automatically be the answer in
the critically ill. Even with these limitations the technology is enticing and
results fascinating. We are uncovering previously undescribed dysfunction and
although it currently is essentially a research-based activity, there is great
promise as a clinical tool as echocardiography analysis becomes more automated,
and potentially speckle tracking echocardiography could help describe cardiac
function in critical illness more accurately than is possible with current
techniques.
PMID- 27608337
TI - Anaesthetic management of obese parturients: what is the evidence supporting
practice guidelines?
AB - Increasing rates of obesity in western populations present management
difficulties for clinicians caring for obese pregnant women. Various governing
bodies have published clinical guidelines for the care of obese parturients.
These guidelines refer to two components of anaesthetic care: anaesthetic
consultation in the antenatal period for women with a body mass index (BMI) >= 40
kg/m2 and the provision of early epidural analgesia in labour. These
recommendations are based on the increased incidence of obstetric complications
and the predicted risks and difficulties in providing anaesthetic care. The
concept behind early epidural analgesia is logical-site the epidural early, use
it for surgical anaesthesia and avoid general anaesthesia if surgery is required.
Experts support this recommendation, but there is weak supporting evidence. It is
known that the management of labour epidurals in obese women is complicated and
that women with extreme obesity require higher rates of general anaesthesia.
Anecdotally, anaesthetists view and apply the early epidural recommendation
inconsistently and the acceptability of early epidural analgesia to pregnant
women is variable. In this topic review, we critically appraise these two
practice recommendations. The elements required for effective implementation in
multidisciplinary maternity care are considered. We identify gaps in the current
literature and suggest areas for future research. While prospective cohort
studies addressing epidural extension ('top-up') in obese parturients would help
inform practice, audit of local practice may better answer the question "is early
epidural analgesia beneficial to obese women in my practice?".
PMID- 27608338
TI - Does objective measurement of tracheal tube cuff pressures minimise adverse
effects and maintain accurate cuff pressures? A systematic review and meta
analysis.
AB - Correct inflation pressures of the tracheal cuff are recommended to ensure
adequate ventilation and prevent aspiration and adverse events. However there are
conflicting views on which measurement to employ. The aim of this review was to
examine whether adjustment of cuff pressure guided by objective measurement,
compared with subjective measurement or observation of the pressure value alone,
was able to prevent patient-related adverse effects and maintain accurate cuff
pressures. A search of PubMed, Web of Science, Embase, CINAHL and ScienceDirect
was conducted using keywords 'cuff pressure' and 'measure*' and related synonyms.
Included studies were randomised or pseudo-randomised controlled trials
investigating mechanically ventilated patients both in the intensive care unit
and during surgery. Outcomes included adverse effects and the comparison of
pressure measurements. Pooled analyses were performed to calculate risk ratios,
effect sizes and 95% confidence intervals. Meta-analysis found preliminary
evidence that adjustment of cuff pressure guided by objective measurement as
compared with subjective measurement or observation of the pressure value alone,
has benefit in preventing adverse effects. These included cough at two hours
(odds ratio [OR] 0.42, confidence interval [CI] 0.23 to 0.79, P=0.007),
hoarseness at 24 hours (OR 0.49, CI 0.31 to 0.76, P <0.002), sore throat (OR
0.73, CI 0.54 to 0.97, P <0.03), lesions of the trachea and incidences of silent
aspiration (P=0.001), as well as maintaining accurate cuff pressures (Hedges' g
1.61, CI 2.69 to 0.53, P=0.003). Subjective measurement to guide adjustment or
observation of the pressure value alone may lead to patient-related adverse
effects and inaccuracies. It is recommended that an objective form of measurement
be used.
PMID- 27608340
TI - Use of the Montreal Cognitive Assessment test to investigate the prevalence of
mild cognitive impairment in the elderly elective surgical population.
AB - Postoperative cognitive disorders are common in elderly patients. Pre-existing
cognitive impairment including mild cognitive impairment may be an important risk
factor for developing postoperative cognitive dysfunction and may not be detected
in a standard preoperative interview, yet is not routinely sought. Our primary
aim was to estimate the prevalence of mild cognitive impairment among elderly
patients presenting to our hospital for elective surgery using a simple
established screening tool: the Montreal Cognitive Assessment test. Secondarily,
we wished to determine the proportion of patients with mild cognitive impairment
who presented with this information available, the effect of increasing age on
the prevalence of mild cognitive impairment and whether the timing and location
of testing influenced results. We used the Montreal Cognitive Assessment test to
screen preoperative patients aged 65 years and over. Our results suggested a
potential prevalence of mild cognitive impairment of 56%, with prevalence
increasing with age. No patients in the sample had a recorded diagnosis of mild
cognitive impairment. Testing in either the preadmission clinic or on admission
on the day of surgery yielded similar results. We found the Montreal Cognitive
Assessment test to be a simple screening tool that was easily administered during
the pre-admission visit.
PMID- 27608339
TI - Cytomegalovirus infection in patients with sepsis due to bloodstream infections:
lower risk and better outcomes in new versus already hospitalised intensive care
unit admissions.
AB - Few studies have examined cytomegalovirus (CMV) reactivation exclusively in
immunocompetent patients with sepsis due to bloodstream infections. In a cohort
of CMV-seropositive critically ill otherwise non-immunosuppressed patients with
sepsis due to bloodstream infection, weekly testing for CMV viraemia was
performed. Outcomes were assessed at 30 days or until death/discharge from the
intensive care unit (ICU). CMV viraemia developed in 20% (20/100) of the
patients. Age (P=0.044) and blood transfusions (P=0.022) were significantly
associated with CMV viraemia. There was no difference in the primary endpoint
(mortality and/or multi-organ failure) between patients with and without CMV
viraemia (P=0.49). However, CMV viraemia was associated with significantly fewer
ICU-free days (P=0.023) and fewer ventilator-free days (P=0.031). Patients
hospitalised in the ICU for more than 48 hours prior to the onset of bloodstream
infection were more likely to develop CMV viraemia (P=0.006), have high-grade
viraemia (P=0.010), and fewer ICU-free days (P=0.018) and ventilator-free days
(P=0.029) than those admitted within 48 hours of bloodstream infection. Thus, CMV
reactivation was associated with fewer ICU- and ventilator-free days, however
overall mortality was not affected. Patients already in the ICU at the onset of
sepsis had higher risk of CMV reactivation and worse outcomes than new ICU-bound
patients suggesting that a targeted approach for interventions for CMV could
conceivably be directed towards those with a more protracted course of illness.
PMID- 27608341
TI - The effects of residual pump blood on patient plasma free haemoglobin levels post
cardiac surgery.
AB - At the end of cardiopulmonary bypass, there are invariably several hundred
millilitres of residual pump blood in the reservoir, which can either be re
transfused or discarded. The objective of this prospective observational study
was to investigate the quality of the residual pump blood, focusing on plasma
free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients
were included in the study. Forty-nine units of residual pump blood and 58 units
of transfused red blood cell (RBC) concentrates were analysed. The mean
preoperative pfHb of the patients was 0.057 +/- 0.062 g/l, which increased
gradually to 0.55 +/- 0.36 g/l on arrival in the intensive care unit
postoperatively. On the first postoperative day, the mean pfHb had returned to
within the normal range. Our data showed that haemoglobin, haematocrit, and
erythrocyte counts of residual pump blood were approximately 40% of the values in
standardised RBC concentrates. Plasma free haemoglobin was significantly higher
in residual pump blood compared to RBC concentrates, and nearly twice as high as
the pfHb in patient blood samples taken contemporaneously. Our findings indicate
that residual pump blood pfHb levels are markedly higher compared to patients'
blood and RBC concentrates, but that its administration does not significantly
increase patients' pfHb levels.
PMID- 27608342
TI - Optimal flexible laryngeal mask airway size in children weighing 10 to 20 kg.
AB - This prospective, randomised study was conducted to assess the effect of flexible
laryngeal mask airway (FLMA) size on oropharyngeal leak pressure (OLP) in
children at the recommended intracuff pressure. A total of 120 children
undergoing elective ophthalmic surgery were randomly assigned to the size 2 FLMA
group or size 2.5 FLMA group. The primary measurement was OLP at an intracuff
pressure of 40 cmH2O. Secondary outcomes included the incidence of OLP <10 cmH2O,
insufficient ventilation, gastric insufflation, insertion time, successful first
attempt insertion rate, fibreoptic view grade and pharyngolaryngeal adverse
events. The median OLP was comparable for the size 2 and size 2.5 FLMA (18 cmH2O
versus 18 cmH2O, P=0.38). However, the size 2 FLMA group had a higher incidence
of OLP <10 cmH2O and insufficient ventilation (13.3% versus 0, P=0.006). In
subgroup analyses based on weight, the size 2.5 FLMA had a lower occurrence of
OLP <10 cmH2O and insufficient ventilation (27% versus 0, P=0.0046) in children
16-20 kg. We conclude that at a 40 cmH2O intracuff pressure, the OLP with the
size 2 and size 2.5 FLMA was similar in children weighing 10-15.9 kg. However, in
children weighing 16-20 kg, size 2 devices had a higher incidence of low OLP and
insufficient ventilation, so a 2.5 FLMA may be preferable in this subgroup.
PMID- 27608343
TI - The minimal leak test technique for endotracheal cuff maintenance.
AB - Endotracheal tube (ETT) cuff pressure management is an essential part of airway
management in intubated and mechanically ventilated patients. Both under- and
over-inflation of the ETT cuff can lead to patient complications, with an ideal
pressure range of 20-30 cmH2O defined. A range of techniques are employed to
ensure adequate ETT cuff inflation, with little comparative data. We performed an
observational cross-sectional study in a tertiary metropolitan ICU, assessing the
relationship between the minimal leak test and cuff manometry. Forty-five
mechanically ventilated patients, over a three-month period, had ETT cuff
manometry performed at the same time as their routine cuff maintenance (minimal
leak test). Bedside nurse measurements were compared with investigator
measurements. At the endpoint of cuff inflation, 20 of 45 patients (44%) had cuff
pressures between 20 and 30 cmH2O; 11 of 45 patients (24%) had cuff pressures <20
cmH2O; 14 of 45 patients (31%) had cuff pressures >=30 cmH2O. Univariate analysis
demonstrated an association between both patient obesity and female gender
requiring less ETT cuff volume (P=0.008 and P <0.001 respectively), though this
association was lost on multivariate analysis. No association was demonstrated
between any measured variables and cuff pressures. Inter-operator reliability in
performing the minimal leak test showed no evidence of bias between nurse and
investigators (Pearson coefficient = 0.897). We conclude the minimal leak test
for maintenance of ETT cuffs leads to both over- and under-inflation, and
alternative techniques, such as cuff manometry, should be employed.
PMID- 27608344
TI - The Alfred Hospital experience of resumption of cardiac activity after withdrawal
of life-sustaining therapy.
AB - With the advent of donation after circulatory death programs in Australia and New
Zealand, greater knowledge is needed about physiologic variation in haemodynamic
activity following withdrawal of cardiorespiratory support. The ANZICS Statement
on Death and Organ Donation allows provision for variation in the observation
times between two and five minutes after cessation of the circulation prior to
declaration of death. We report our experience of two cases, the first where
electrical activity and pulse returned after a 102 second pause and the second
where electrical activity returned after a three minute pause; both longer than
previously reported cases.
PMID- 27608345
TI - The utility of procalcitonin in the prediction of serious bacterial infection in
a tertiary paediatric intensive care unit.
AB - To determine utility of procalcitonin (PCT) for the prediction of bacterial
infection in critically ill children, we analysed the relationship between serum
PCT, cultures and other laboratory markers of bacterial sepsis or viral infection
in a tertiary paediatric intensive care unit (PICU). The outcome measures were
levels of PCT in proven bacteraemia, pneumonia and viral respiratory infection;
and comparison of PCT to immature to total neutrophil ratio (ITR) in prediction
of bacteraemia. In 420 children with suspected sepsis, 1,226 serum PCT levels
were analysed. Children with bacteraemia had a higher median PCT (2.03 ng/ml,
interquartile range [IQR] 0.67-42.4) than those who did not have bacteraemia
(0.82 ng/ml, IQR 0.295-2.87) (P=0.033). PCT was a significant but only moderate
predictor of bacteraemia (AUC 0.65). In 866 episodes of suspected sepsis where
paired PCT and ITR were performed, the median ITR in children with bacteraemia
was 0.19 ng/ml (IQR 0.04-0.35), and the median PCT was 6.5 ng/ml (IQR 0.71-61.8).
PCT was a marginally better predictor of bacteraemia (AUC 0.69) than the ITR (AUC
0.66). In children with viral respiratory tract infection only, the median PCT
was 1.26 ng/ml (0.35-5.5), and in those with likely bacterial pneumonia the
median PCT was 0.80 ng/ml (IQR 0.28-1.70). In a heterogeneous population of
children in a tertiary PICU, PCT measured at a single timepoint was a moderate
predictor of proven bacteraemia. In our population PCT did not reliably identify
localised bacterial infection or distinguish bacterial from viral respiratory
infection.
PMID- 27608346
TI - Local anaesthetic toxicity after bilateral thoracic paravertebral block in
patients undergoing coronary artery bypass surgery.
AB - We conducted a small pilot observational study of the effects of bilateral
thoracic paravertebral block (BTPB) as an adjunct to perioperative analgesia in
coronary artery bypass surgery patients. The initial ropivacaine dose prior to
induction of general anaesthesia was 3 mg/kg, which was followed at the end of
the surgery by infusion of ropivacaine 0.25% 0.1 ml/kg/hour on each side (e.g.
total 35 mg/hour for a 70 kg person). The BTPB did not eliminate the need for
supplemental opioids after CABG in the eight patients studied. Moreover, in spite
of boluses that were within the manufacturer's recommendation for epidural and
major nerve blocks, and an infusion rate that was only slightly higher than what
appeared to be safe for epidural infusion, potentially toxic total plasma
ropivacaine concentrations were common. We also could not exclude the possibility
that the high ropivacaine concentrations were contributing to postoperative
mental state changes in the postoperative period. Also, one patient developed
local anaesthetic toxicity after the bilateral paravertebral dose. As a result,
the study was terminated early after four days. The question of whether
paravertebral block confers benefits in cardiac surgery remains unanswered.
However, we believe that the bolus dosage and the injection rate we used for BTPB
were both too high, and caution other clinicians against the use of these doses.
Future studies on the use of BTPB in cardiac surgery patients should include
reduced ropivacaine doses injected over longer periods.
PMID- 27608347
TI - Anaesthetists' experiences with the early labour epidural recommendation for
obese parturients: a qualitative study.
AB - Caring for obese pregnant women presents challenges for all medical
professionals. Despite a lack of supporting evidence, expert opinion and
international guidelines suggest early labour epidural insertion for obese women.
Anecdotally this is not supported by all anaesthetists. This qualitative study
explored the experiences of anaesthetists regarding early epidural analgesia in
obese parturients, to answer the research question: Are anaesthetists consistent
in how they apply early epidural analgesia in obese parturients? Personal in
depth interviews with 42 specialist anaesthetists working in south-east
Queensland, Australia, were completed between February and April, 2015.
LeximancerTM text analysis software applied a validated algorithm to the data to
identify themes and concepts. The major themes were explored by the first author
to answer the research question. Three major themes were identified: the demands
associated with caring for obese women; concern regarding the anaesthetic
technique used in obese women; and the importance of communication with obstetric
staff. Disagreement regarding interpretation and application of early epidural
analgesia was identified within this group of anaesthetists. These anaesthetists
were inconsistent in how they interpreted and applied early epidural analgesia
for obese parturients, with some questioning the validity of the practice. The
combination of uncertainty, urgency and technical difficulty presented by obese
parturients provoked anxiety in these clinicians, particularly the anticipation
of unplanned general anaesthesia. Consistent anaesthetic practice could improve
the implementation of early epidural analgesia in obese parturients.
PMID- 27608348
TI - Novel transoesophageal echocardiographic views attain superior incident angles
for tricuspid, but not pulmonary, valvular Doppler interrogation.
AB - For accurate spectral Doppler valvular evaluation, intraoperative sonographers
must use transoesophageal echocardiographic (TOE) views that offer optimal
incident angles. We hypothesised that views added to the 2013 American Society of
Echocardiography/Society of Cardiovascular Anesthesiologists (ASE/SCA) standard
views and other novel views we have described of the tricuspid (TV) and pulmonary
valves (PV) offered superior incident angles to those included in the original
1999 ASE/SCA recommendations for comprehensive intraoperative TOE examination. We
compared the acquisition feasibility and incident angles obtained by these views
in 62 patients undergoing elective cardiac surgery, who received TOE monitoring
as standard care. Overall, the 2013 ASE/SCA standard and novel views provided
superior incident angles for the TV (28% and 66% of patients) whereas the 1999
ASE/SCA standard views provided superior incident angles for the PV (79% of
patients, P <0.0001). The novel 90 degrees mid-oesophageal modified bicaval view
(90 degrees MEMBC) and the 1999 ASE/SCA standard aortic arch short-axis view
(AoArSAX) obtained best incident angles for the TV (mean [95% confidence
interval] 13 degrees [10 degrees -16 degrees ]) and PV (5 degrees [3 degrees -7
degrees ]) respectively. PV view acquisition feasibility between the 1999 ASE/SCA
standard, 2013 ASE/SCA standard and novel views was not significantly different
(acquisition rate difference 11%, P >=0.11). We conclude that the 2013 ASE/SCA TV
standard and novel views obtained superior incident angles for the tricuspid, but
not pulmonary valves. We recommend that intraoperative sonographers consider the
use of these views, particularly when incident angles obtained with standard
views are suboptimal.
PMID- 27608349
TI - Haemorrhagic putaminal necrosis, optic atrophy and coma: a triad suggestive of
methanol poisoning.
PMID- 27608350
TI - Unexpected left atrial reinfusion through a patent foramen ovale during
venovenous extracorporeal life support.
PMID- 27608351
TI - Continuous electroencephalograph monitoring in the intensive care unit.
PMID- 27608352
TI - Possible abnormal response to rocuronium in a patient taking multiple fitness
supplements.
PMID- 27608353
TI - Evaluation of perioperative predictors of acute kidney injury post orthotopic
liver transplantation.
PMID- 27608354
TI - A cheap fix for an expensive problem: the use of a thermoplastic mouthguard to
reduce the risk of dental trauma during orotracheal intubation.
PMID- 27608356
TI - Bariatric surgery and the gastric tube-caution for the unwary anaesthetist.
PMID- 27608355
TI - Type I and II pectoral nerve blocks with serratus plane block for awake video
assisted thoracic surgery.
PMID- 27608357
TI - Regional nerve blockade in an Australian tertiary paediatric centre.
PMID- 27608358
TI - Use of the C-MAC(r) adult D blade in paediatric patients with Nager syndrome.
PMID- 27608359
TI - Differential Activation Patterns in the Same Brain Region Led to Opposite
Emotional States.
AB - In human studies, how averaged activation in a brain region relates to human
behavior has been extensively investigated. This approach has led to the finding
that positive and negative facial preferences are represented by different brain
regions. However, using a functional magnetic resonance imaging (fMRI) decoded
neurofeedback (DecNef) method, we found that different patterns of neural
activations within the cingulate cortex (CC) play roles in representing opposite
directions of facial preference. In the present study, while neutrally preferred
faces were presented, multi-voxel activation patterns in the CC that corresponded
to higher (or lower) preference were repeatedly induced by fMRI DecNef. As a
result, previously neutrally preferred faces became more (or less) preferred. We
conclude that a different activation pattern in the CC, rather than averaged
activation in a different area, represents and suffices to determine positive or
negative facial preference. This new approach may reveal the importance of an
activation pattern within a brain region in many cognitive functions.
PMID- 27608360
TI - Boosting recovery rather than buffering reactivity: Higher stress-induced
oxytocin secretion is associated with increased cortisol reactivity and faster
vagal recovery after acute psychosocial stress.
AB - Animal models and human studies using paradigms designed to stimulate endogenous
oxytocin release suggest a stress-buffering role of oxytocin. We here examined
the involvement of stress-induced peripheral oxytocin secretion in reactivity and
recovery phases of the human psychosocial stress response. Healthy male and
female participants (N=114) were subjected to a standardized laboratory stressor,
the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was
assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity,
alpha-amylase and heart rate as markers of sympathetic activity, high frequency
heart rate variability as a marker of vagal tone and self-rated anxiety as an
indicator of subjective stress experience. On average, oxytocin levels increased
by 51% following psychosocial stress. The stress-induced oxytocin secretion,
however, did not reduce stress reactivity. To the contrary, higher oxytocin
secretion was associated with greater cortisol reactivity and peak cortisol
levels in both sexes. In the second phase of the stress response the opposite
pattern was observed, with higher oxytocin secretion associated with faster vagal
recovery. We suggest that after an early stage of oxytocin and HPA-axis co
activation, the stress-reducing action of oxytocin unfolds. Due to the time lag
it manifests as a recovery-boosting rather than a reactivity-buffering effect. By
reinforcing parasympathetic autonomic activity, specifically during stress
recovery, oxytocin may provide an important protective function against the
health-compromising effects of sustained stress.
PMID- 27608361
TI - Full-term deliveries without antecedent labor reveal sex differences in umbilical
cord glucocorticoid concentrations.
AB - BACKGROUND: Previous studies have shown that pregnant women have higher salivary
cortisol levels when the fetus is female. These findings suggest a basis for the
sex differences observed in many offspring outcomes after exposure to in utero
stress, but it is not known if fetal adrenal glucocorticoid synthesis differs by
sex. METHODS: Arterial and venous umbilical cord blood samples were collected
immediately after scheduled cesarean delivery (n=52, 25 female). Cortisol and
corticosterone concentrations were quantified by liquid chromatography coupled to
tandem mass spectrometry. RESULTS: Sex differences were observed for fetal
arterial and venous cortisol and venous corticosterone, with higher levels
present when the fetus was female. However, sex differences were not observed for
fetal synthesis of cortisol, suggesting that the fetus does not control the
differences observed in cord blood glucocorticoids. CONCLUSIONS: The presence of
sex differences in umbilical cord glucocorticoid concentrations in the absence of
sex differences in glucocorticoid synthesis by the fetal adrenal gland suggests
that these differences have a maternal or placental origin. Thus, the in utero
glucocorticoids in circulation are sex-specific and may have developmental
importance for sex differences in psychiatric and neurodevelopment disorders that
display sex biases.
PMID- 27608362
TI - Progesterone: The neglected hormone in schizophrenia? A focus on progesterone
dopamine interactions.
AB - Sex differences appear to be an important factor in schizophrenia. Women with
schizophrenia tend to exhibit less disease impairment than men, typically
presenting with a later age-at-onset, lower overall incidence and less severe
symptoms. These observations underpin the estrogen hypothesis of schizophrenia,
which postulates a protective role of estrogen against the development and
severity of the disorder. While there has been significant attention placed on
the impact of estrogens in schizophrenia, less consideration has been afforded to
the role of progesterone, the other main female gonadal hormone. This narrative
review discusses the role of progesterone as a neuroactive steroid and how it may
be dysregulated in schizophrenia. Preclinical and molecular studies relevant to
schizophrenia are discussed with a particular focus on the interactions between
progesterone and the dopaminergic system. Notably, existing data on progesterone
in relation to schizophrenia is inconsistent, with some studies suggesting a
neuroprotective role for the hormone (e.g. animal models of cognitive dysfunction
and positive symptoms), while other studies posit a disruptive impact of the
hormone (e.g. negative correlations with symptom modulation in patients). This
review aims to thoroughly address these discrepancies, concluding that altogether
the data suggest that progesterone is a key modulator of central systems
implicated in schizophrenia. On this basis, we argue that a more inclusive,
considered effort of future studies to understand the intricacies of the
interactions between progesterone and estrogen. Such an effort may enhance our
understanding of the roles of sex hormones in schizophrenia, thus leading to
avenues for novel therapeutic approaches.
PMID- 27608364
TI - Expression of IL-6, IL-10, IL-17 and IL-33 in the peri-implant crevicular fluid
of patients with peri-implant mucositis and peri-implantitis.
AB - OBJECTIVES: The aim of this study was to compare the levels of IL-6, IL-10, IL-17
and IL-33 in the peri-implantar crevicular fluid (PICF) and in parotid gland
saliva (PGS) of healthy patients, and peri-implantitis and peri-implant mucositis
patients. MATERIALS AND METHODS: The PICF was collected from 40 implants as
follows: 10 peri-implant mucositis patients, 20 peri-implantitis patients and 10
healthy patients. The PICF and PGS samples collected from each patient were
quantified for IL-6, IL-10, IL-17 and IL-33 by enzymatic immunosorbent assay
(ELISA). RESULTS: IL-6, IL-17 and IL-33 levels on PIFC were significantly higher
in peri-implantitis group when compared to healthy group. IL-17 and IL-33 levels
in PIFC were significantly higher in peri-implant mucositis group than in healthy
group. There was no significant difference when comparing IL-6, IL-10, IL-17 and
IL-33 levels in PGS among healthy, peri-implant mucositis and peri-implantitis
groups. CONCLUSIONS: Therefore, as in patients with peri-implantitis there were
significantly higher levels of IL-6, IL-17 and IL-33 in PICF, we believe that
these cytokines were intensifying local inflammatory process, and contributing to
clinical aspects such as increased marginal bleeding and probing depth found in
patients with peri-implantitis. Furthermore, as IL-17 and IL-33 were increased in
patients with peri-implant mucositis, hypothesized that these cytokines were also
contributing to the inflammatory process observed in this disease.
PMID- 27608363
TI - Interleukin-4 released from human gingival fibroblasts reduces
osteoclastogenesis.
AB - OBJECTIVE: Human gingival epithelium is continuously exposed to bacteria and acts
as the first line of defense in periodontal tissues. It is crucial to maintain
healthy, non-inflamed gingival tissue to avoid gingivitis and periodontitis. The
purpose of this study was to investigate the influence of IL-4 in human gingival
fibroblasts (hGF) on the activation of osteoclasts. DESIGN: Two hGF samples were
obtained from two healthy patients, and one was collected from a commercially
available resource. The hGFs were cultured, and conditioned medium of hGF (hGF
CM) was stocked at -80 degrees C. The mRNA was isolated from the hGF cultures and
analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) for
expression of suppressive osteoclastogenetic mediators, such as interleukin (IL)
4, osteoprotegerin (OPG), IL-10, IL-27, and IL-33. The hGF-CM was used to
investigate the inhibitory function of mouse macrophages supplemented with either
glutathione S-transferase-Receptor activator of NF-kB ligand (GST-RANKL), human
recombinant (rh)IL-4, or rhOPG but not a combination. Differentiation of
osteoclasts was examined by tartrate resistant acid phosphatase (TRAP) staining
and TRAP assay. The suppressive role of IL-4 was assessed by neutralizing IL-4
antibody in the TRAP assay. RESULTS: The hGF-CM reduced both TRAP positive
staining and activity in a dose-dependent manner. IL-4 and OPG mRNA expressions
were expressed in hGF-CM from three different donors but that of IL-10, IL-27, or
IL-33 was not detected. In the RAW264 culture, rhIL-4 and rhOPG reduced TRAP
positive staining as well as activity in a dose-dependent manner. Moreover,
addition of neutralizing antibodies for IL-4 reduced the inhibitory effect of
conditioned medium from gingival fibroblasts in the RAW264 culture. CONCLUSION:
We concluded that hGF potentially contained suppressive mediators, such as IL-4
and OPG, for osteoclastogenesis. Moreover, we confirmed that the differential
inhibition of osteoclast is caused by OPG as well as IL-4 in hGF-CM.
PMID- 27608366
TI - Monitoring of topical corticosteroid phobia in a population of parents with
children with atopic dermatitis using the TOPICOP(r) scale: prevalence, risk
factors and the impact of therapeutic patient education.
PMID- 27608367
TI - Reactivity of Two-Dimensional Au9, Pt9, and Au18Pt18 against Common Molecules.
AB - Adsorption of common molecules over two-dimensional Au9, Pt9, and Au18Pt18 is
investigated with implementation of first-principles calculations. In general, it
is found that Pt9 and Au18Pt18 exhibit low adsorption energies where Au18Pt18
preserves the structural integrity of the molecule and surface. In particular,
adsorption of molecules onto Au18Pt18 frequently results in low adsorption
energies and high reactivity with minor surface reconstruction of Au18Pt18 and
average bond lengths of molecules. The decrease in adsorption energy can be
attributed to the presence of platinum, while gold can be considered responsible
for structural stability. In addition, molecule dissociation is observed in the
cases of H2, HCl, CH4, SO, and SO2 when Pt atoms are involved. Thus, two
dimensional Au9, Pt9, and Au18Pt18 show low adsorption energies against common
molecules, reflecting adsorption energies observed in small Au and Pt clusters.
These results demonstrate that Au18Pt18 can successfully utilize the low
adsorption energies associated with platinum while preserving the integrity of
the surface structure using gold atoms, making it possible to adsorb desired
molecules using select areas of the Au18Pt18 surface.
PMID- 27608365
TI - Effect of dietary calcium deficiency and altered diet hardness on the jawbone
growth: A micro-CT and bone histomorphometric study in rats.
AB - OBJECTIVES: We examined the effects of a low-calcium diet and altered diet
hardness on bone architecture and metabolism in the maxilla and mandible.
MATERIALS AND METHODS: Male rats (n=48, 3 weeks old) were divided into six
groups. In total, 24 rats were given a normal-calcium diet and the others were
given a low-calcium diet. Each group was then divided into three subgroups, which
were fed a 'hard diet for 8 weeks, a 'soft die for 8 weeks, or switched from the
soft diet after 4 weeks to the hard diet for 4 weeks. The bone architecture was
analyzed using cephalometry and micro-computed tomography, in addition, the bone
metabolism was analyzed using serum bone markers and bone histomorphometry in the
maxilla and mandible. Moreover, the bone formation patterns were evaluated using
histopathologically in the midpalatal suture. RESULTS: The low-calcium diet
affected bone architecture by increasing bone turnover and the soft diet affected
bone architecture mainly by increasing bone resorption. The soft diet changed the
chondrocyte cell layers into fibrous connective tissues in the midpalatal suture.
At 4 weeks after the return to a hard diet from a soft diet, recovery of the
deterioration in bone architectures was seen in the maxilla and mandible.
CONCLUSIONS: We demonstrated that mastication with a hard diet is effective for
recovering the collapsed equilibrium of jaw bone turnover and the deteriorating
jaw bone architectures due to the poor masticatory function during the growing
period.
PMID- 27608368
TI - Effectiveness of a Brief Home-Based Social Work Motivational Intervention for
Male Methamphetamine Users in Tehran: A Randomized Clinical Trial.
AB - Methamphetamine, a highly addictive psychostimulant drug, is widely used by
substance users who are not motivated to undergo treatment throughout the world,
including Iran. This research was conducted to evaluate the effectiveness of a
brief home-based social work motivational intervention (HSWMI) to encourage male
methamphetamine users to participate in a treatment program. METHOD: Fifty-six
unmotivated male methamphetamine users participated in a randomized controlled
trial. The case group received the HSWMI in addition to the usual consulting
services in the clinic; the control group just received the usual consulting
services. Data were collected 7 and 90 days after the intervention to evaluate
participation and retention in a treatment program. Data were analyzed using the
chi-square test. RESULTS: Drug users with a mean age of 32.55 years and mean
duration of drug use of 7.73 years, participated in the case (n = 28) and control
(n = 28) groups. The case group participated in treatment programs significantly
more than the control group and the retention rate for the case group was
significantly higher than for the control group. CONCLUSION: This brief HSWMI was
effective to increase the motivation of methamphetamine users to participate and
remain in treatment programs. This intervention can be implemented by social
workers in substance use treatment centers.
PMID- 27608370
TI - Reliable fabrication of sub-10 nm silicon nanowires by optical lithography.
AB - The reliable and controllable fabrication of silicon nanowires is achieved, using
mature CMOS technology processes. This will enable a low-cost route to
integrating novel nanostructures with CMOS logic. The challenge of process
repeatability has been overcome by careful study of material properties for
processes such as etching and oxidation. By controlling anisotropic wet etching
conditions, selection of nitride mask layer properties and sidewall oxidation, a
robust process was achieved to realize silicon nanowires with sub 10 nm features.
Surface roughness of nanowires was improved by a suitable oxidation step. The
influence of process conditions on the shape of the nanowire was studied using
TCAD simulation.
PMID- 27608369
TI - Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at
live poultry markets in China, 2014 and 2015.
AB - Zoonotic infections by avian influenza viruses occur at the human-poultry
interface, but the modes of transmission have not been fully investigated. We
assessed the potential for airborne and fomite transmission at live poultry
markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR),
China, during 2014 and 2015. Viral genome and infectious avian influenza A
viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from
particles larger or equal to 1 MUm in diameter in the air sampled with cyclone
based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza
A(H9N2) viruses were ubiquitously isolated every month during the study period
from air and environmental swabs, and different lineages of H9N2 virus were
isolated from markets where chickens and minor land-based poultry were sold. The
use of de-feathering devices increased the quantity of virus-laden airborne
particles while market closure reduced the amount of such particles. The results
highlight the possibility of airborne transmission of avian influenza viruses
among poultry or from poultry to humans within such settings. This may explain
epidemiological observations in which some patients with H7N9 infection reported
being in markets but no direct contact with live poultry or poultry stalls.
PMID- 27608371
TI - Prevalence and putative risk markers of challenging behavior in students with
intellectual disabilities.
AB - Numerous studies have reported a high prevalence of challenging behavior among
students with intellectual disabilities (ID). They discuss different putative
risk markers as well as their influence on the occurrence of challenging
behavior. The study investigates the prevalence of challenging behavior and
evaluates in terms of a replication study well-known putative risk markers among
a representative sample of students with ID (N=1629) in Bavaria, one of the
largest regions in Germany. The research is based on a modified version of the
Developmental Behavior Checklist (DBC). Findings indicate a prevalence rate of
52% for challenging behavior. The following putative risk markers are associated
with challenging behavior: intense need for care, male gender, lack of
communication skills, and residential setting. These risk markers explain 8.4% of
the variance concerning challenging behavior. These results reveal that
challenging behavior either is to a large extent determined by situations and
interactions between individuals and environment and cannot be explained by the
measured individual and social risk markers alone, or it is determined by further
risk markers that were not measured.
PMID- 27608372
TI - Benefits of simultaneous bilateral cochlear implantation on verbal reasoning
skills in prelingually deaf children.
AB - BACKGROUND: Impaired auditory speech perception abilities in deaf children with
hearing aids compromised their verbal intelligence enormously. The availability
of unilateral cochlear implantation (CI) auditory speech perception and spoken
vocabulary enabled them to reach near ageappropriate levels. This holds
especially for children in spoken language environments. However, speech
perception in complex listening situations and the acquisition of complex verbal
skills remains difficult. Bilateral CI was expected to enhance the acquisition of
verbal intelligence by improved understanding of speech in noise. METHODS: This
study examined the effect of bilateral CI on verbal intelligence of 49 deaf
children (3;5-8;0 years). Relations between speech perception in noise, auditory
short-term memory and verbal intelligence were analysed with multiple linear
regressions. In addition, the interaction of educational setting, mainstream or
special, on these relations was analysed. RESULTS: Children with bilateral CI
obtained higher scores on verbal intelligence. Significant associations were
present between speech perception in noise, auditory short-term memory and verbal
intelligence. CONCLUSION: Children with simultaneous bilateral CIs showed better
speech perception in noise than children with unilateral CIs, which mediated by
the auditory short-term memory capacity, enhanced the ability to acquire more
complex verbal skills for BICI children in mainstream education.
PMID- 27608413
TI - Tight Junction Protein Abundance and Apoptosis During Involution of Rat Mammary
Glands.
AB - To examine tight junction protein abundance and apoptosis of epithelial cells at
the onset of involution in rodent mammary glands, milk accumulation and mammary
engorgement were induced by teat-sealing with an adhesive for 0, 6, 12, 18, 24,
and 36 h (n = 6 per group) at peak lactation. In non-sealed control glands,
histological analysis confirmed a lactating phenotype, indicating suckling by
pups throughout the experiment. In contrast, alveoli of teat-sealed glands were
distended within 6 h, with maximal luminal size observed by 12 h of non-suckling.
By 18 h following teat-sealing, an involuting phenotype was observed, indicated
by alveolar lumina engorged with milk vesicles and increased leukocytes. Relative
to non-sealed glands, mammary apoptosis was increased in engorged glands 18 h
following teat-sealing. The abundance of ZO-1 and occludin proteins was decreased
in engorged glands by 12 and 18 h, respectively, following teat-sealing. In
contrast, the claudin-1 22 kDa band was increased by 6 h and peaked at 12-18 h,
whereas the 28 kDa band declined by 36 h, relative to controls. There were no
temporal changes in ZO-1, occludin, and claudin-1 22 kDa proteins within control
glands, although there were minor differences in claudin-1 28 kDa. These data
indicate that intramammary milk accumulation due to cessation of milk removal is
associated with mammary apoptosis. The apoptotic event is preceded by a rapid
loss of abundance of ZO-1, occludin and an initial increase in claudin-1. The
loss of cell-cell communication may initiate involution and apoptosis of mammary
epithelial cells and is a localized intramammary event, occurring only in non
suckled glands. J. Cell. Physiol. 232: 2075-2082, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27608412
TI - Lytic transglycosylases LtgA and LtgD perform distinct roles in remodeling,
recycling and releasing peptidoglycan in Neisseria gonorrhoeae.
AB - Neisseria gonorrhoeae releases peptidoglycan (PG) fragments during infection that
provoke a large inflammatory response and, in pelvic inflammatory disease, this
response leads to the death and sloughing of ciliated cells of the Fallopian
tube. We characterized the biochemical functions and localization of two enzymes
responsible for the release of proinflammatory PG fragments. The putative lytic
transglycosylases LtgA and LtgD were shown to create the 1,6-anhydromuramyl
moieties, and both enzymes were able to digest a small, synthetic tetrasaccharide
dipeptide PG fragment into the cognate 1,6-anhydromuramyl-containing reaction
products. Degradation of tetrasaccharide PG fragments by LtgA is the first
demonstration of a family 1 lytic transglycosylase exhibiting this activity.
Pulse-chase experiments in gonococci demonstrated that LtgA produces a larger
amount of PG fragments than LtgD, and a vast majority of these fragments are
recycled. In contrast, LtgD was necessary for wild-type levels of PG precursor
incorporation and produced fragments predominantly released from the cell.
Additionally, super-resolution microscopy established that LtgA localizes to the
septum, whereas LtgD is localized around the cell. This investigation suggests a
model where LtgD produces PG monomers in such a way that these fragments are
released, whereas LtgA creates fragments that are mostly taken into the cytoplasm
for recycling.
PMID- 27608414
TI - Multifunctional AIEgens for Future Theranostics.
AB - The combination of diagnosis and therapeutics into one theranostics system has
attracted great interest in life science and biomedical fields. The current
theranostic platform largely relies on the integration of multiple materials with
different functionalities. The all-in-one approach has the risk of high
complicity with reduced reproducibility. Smart design of simple molecules born
with multifunctions should represent one of the future directions in
theranostics. Fluorogens with aggregation-induced emission (AIEgens) are one type
of such smart materials, which have attracted increasing attentions in recent
years. In this concept, the key frontier developments of simple AIEgens with
multifunctions for imaging and therapy are presented, which include fluorescence
photoacoustic imaging, fluorescence-magnetic resonance imaging, fluorescence
image-guided photodynamic therapy, fluorescence image-guided chemotherapy and
photoacoustic image-guided photothermal therapy. The smart molecular design to
endow each AIEgen with strong capability to simultaneously offer two or more
theranostic functions should attract more scientists into this exciting research
direction.
PMID- 27608415
TI - Genetic alterations related to BRAF-FGFR genes and dysregulated MAPK/ERK/mTOR
signaling in adult pilocytic astrocytoma.
AB - Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior.
However, their underlying molecular-genetic events are largely uncharacterized.
Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were
studied (MIB-1 LI: 1%-5%). Analysis of BRAF alterations using qRT-PCR, confirmed
KIAA1549-BRAF fusion in 11 (19%) and BRAF-gain in 2 (3.4%) cases. BRAF-V600E
mutation was noted in 1 (1.7%) case by sequencing. FGFR1-mutation and FGFR-TKD
duplication were seen in 7/59 (11.9%) and 3/59 (5%) cases, respectively. Overall
36% of APAs harbored BRAF and/or FGFR genetic alterations. Notably, FGFR related
genetic alterations were enriched in tumors of supratentorial region (8/25, 32%)
as compared with other locations (P = 0.01). The difference in age of cases with
FGFR1-mutation (Mean age +/- SD: 37.2 +/- 15 years) vs. KIAA1549-BRAF fusion
(Mean age +/- SD: 25.1 +/- 4.1 years) was statistically significant (P = 0.03).
Combined BRAF and FGFR alterations were identified in 3 (5%) cases. Notably, the
cases with more than one genetic alteration were in higher age group (Mean age +/
SD: 50 +/- 12 years) as compared with cases with single genetic alteration (Mean
age +/- SD: 29 +/- 10; P = 0.003). Immunopositivity of p-MAPK/p-MEK1 was found in
all the cases examined. The pS6-immunoreactivity, a marker of mTOR activation was
observed in 34/39 (87%) cases. Interestingly, cases with BRAF and/or FGFR related
alteration showed significantly lower pS6-immunostatining (3/12; 25%) as compared
with those with wild-type BRAF and/or FGFR (16/27; 59%) (P = 0.04). Further,
analysis of seven IDH wild-type adult diffuse astrocytomas (DA) showed FGFR
related genetic alterations in 43% cases. These and previous results suggest that
APAs are genetically similar to IDH wild-type adult DAs. APAs harbor infrequent
BRAF alterations but more frequent FGFR alterations as compared with pediatric
cases. KIAA1549-BRAF fusion inversely correlates with increasing age whereas
FGFR1-mutation associates with older age. Activation of MAPK/ERK/mTOR signaling
appears to be an important oncogenic event in APAs and may be underlying event of
aggressive tumor behavior. The findings provided a rationale for potential
therapeutic advantage of targeting MAPK/ERK/mTOR pathway in APAs.
PMID- 27608417
TI - The promise and pitfalls of the many methods of plasma genotyping.
PMID- 27608416
TI - Acute pulmonary thromboembolism in emergency room: gray-scale versus color
doppler ultrasound evaluation.
AB - BACKGROUND: Pulmonary thromboembolism (PTE) remains under-diagnosed fatal disease
at emergency units suggesting the need for alternative, easy, and noninvasive
bedside diagnostic approaches. OBJECTIVES: To determine the diagnostic role of
gray-scale and color Doppler transthoracic ultrasonography (TUS) in patients with
PTE. PATIENTS AND METHODS: Blinded to 64 multi-detectors CT pulmonary angiography
(MDCTPA) examination as a gold standard, 60 patients with clinically suspected
PTE underwent gray-scale and then color Doppler TUS examination. Results were
compared and diagnostic accuracy of TUS was assessed. RESULTS: Forty patients
proved to have PTE by MDCTPA. TUS showed typical lesions in 33 patients with the
mean of 2 lesions per patient. Most lesions were hypoechoic, wedge- shaped, and
pleural- based and the majority (80%) was located in the lower lobes.
Consolidation with little perfusion was detected by Color Doppler ultrasound in
97% of lesions. Isolated central PTE was significantly higher in TUS negative
patients. For gray -scale TUS, sensitivity, specificity, positive and negative
predictive values and accuracy were 82%, 90%, 94%, 72%, and 85%. Meanwhile the
sensitivity, specificity, positive and negative predictive values and accuracy of
color Doppler TUS were 80%, 95%, 97%, 70% and 87%, respectively. CONCLUSION: TUS
is a reliable diagnostic bedside test for PTE in critically ill and immobile
patients. Adding color Doppler to gray-scale TUS increases the specificity and
accuracy and consequently the confidence in the diagnosis of peripheral pulmonary
infarctions and differentiates them from other pulmonary lesions that allow
initiation of anticoagulants.
PMID- 27608418
TI - Post Hybrid Cochlear Implant Hearing Loss and Endolymphatic Hydrops.
AB - OBJECTIVE: To evaluate for potential causes of delayed loss of residual hearing
that variably occurs with hybrid cochlear implants. STUDY DESIGN:
Histopathological evaluation of 29 human temporal bone (HTB) with cochlear
implant (CI). SETTING: The Neurotology and House HTB Laboratory of UCLA (House
UCLA). SUBJECTS AND METHODS: HTB from CI patients from the House-UCLA HTB
Laboratory (n = 28) and one courtesy of Massachusetts Eye and Ear Infirmary
(MEEI). Histopathological analysis to identify the location of cochleostomy,
fibrosis, and bone formation in the scala vestibuli and tympani, and
endolymphatic hydrops. Spiral ganglion neuron counts were obtained. Statistical
analysis compared presence of cochleostomy and location with the
histopathological findings. RESULTS: Seventeen of 29 bones with fibrosis in the
scala vestibule (SV) and tympani had evidence of a cochleostomy involving the SV
containing the ductus reunions, all of which had hydrops. Ten of 11 bones had no
SV fibrosis, and a cochleostomy limited to the scala tympani, of which all had no
hydrops. One HTB had moderate SV fibrosis not involving the ductus reuniens, and
was without hydrops. One HTB had a SV cochleostomy but the electrode ruptured
Reissner's membrane, and was without hydrops. Cochleostomy was significantly
associated with SV fibrosis and hydrops (p < 0.01), those without hydrops had no
SV atrophy (p < 0.01). Round window insertion was associated with no fibrosis and
no hydrops. CONCLUSION: We hypothesize that cochleostomies involving scala
vestibuli incite fibrosis, compromising the ductus reuniens, causing hydrops
which may cause the delayed loss of residual low frequency hearing in CI.
PMID- 27608420
TI - IL-15 and RANKL Play a Synergistically Important Role in Osteoclastogenesis.
AB - Interleukin-15 (IL-15), a cytokine secreted by several cell types, has important
physiological roles in the activity, proliferation, and viability of immune
cells. It has both chemoattractant and proinflammatory properties, and may
promote bone destruction. A previous study has shown that IL-15 alone exerts no
effect on osteoclastogenesis. Therefore, the current study addressed the
synergistic effect of IL-15 on osteoclast formation using RAW264.7 (RAW) cells by
co-stimulation with receptor activator of nuclear factor (NF)-kappaB ligand
(RANKL) that has a major role in osteoclastogenesis involving the pathogenesis of
rheumatoid arthritis and periodontal disease. Co-stimulation of RAW cells by IL
15 and RANKL significantly increased the gene expression of osteoclast
differentiation and osteoclastogenesis markers compared with stimulation by RANKL
or IL-15 independently as evaluated by tartrate-resistant acid phosphate-positive
cell numbers, the fusion index, a pit formation assay with Alizarin red staining
(calcification estimation), and quantitative polymerase chain reaction.
Phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal
kinase, p38 mitogen-activated protein kinase, and NF-kappaB was significantly
increased by RANKL and IL-15 (P < 0.05) compared with RANKL alone. In addition,
these differentiation activities induced by RANKL and IL-15 were comparatively
suppressed by inhibition of ERK, suggesting that this synergistic effect on
osteoclastogenesis is mainly mediated by ERK. Taken together, our results
demonstrate that IL-15 and RANKL induce osteoclastogenesis synergistically, and
IL-15 might play a novel and major role in destructive inflammatory bone
diseases. J. Cell. Biochem. 118: 739-747, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27608419
TI - Objective and Perceived Weight: Associations with Risky Adolescent Sexual
Behavior.
AB - CONTEXT: Studies have shown that obesity is associated with increased sexual risk
taking, particularly among adolescent females, but the relationships between
obesity, perceived weight and sexual risk behaviors are poorly understood.
METHODS: Integrative data analysis was performed that combined baseline data from
the 1994-1995 National Longitudinal Study of Adolescent Health (from 17,606
respondents in grades 7-12) and the 1997 National Longitudinal Survey of Youth
(from 7,752 respondents aged 12-16). Using six sexual behaviors measured in both
data sets (age at first intercourse, various measures of contraceptive use and
number of partners), cluster analysis was conducted that identified five distinct
behavior clusters. Multivariate ordinal logistic regression analysis examined
associations between adolescents' weight status (categorized as underweight,
normal-weight, overweight or obese) and weight perception and their cluster
membership. RESULTS: Among males, being underweight, rather than normal-weight,
was negatively associated with membership in increasingly risky clusters (odds
ratio, 0.5), as was the perception of being overweight, as opposed to about the
right weight (0.8). However, being overweight was positively associated with
males' membership in increasingly risky clusters (1.3). Among females, being
obese, rather than normal-weight, was negatively correlated with membership in
increasingly risky clusters (0.8), while the perception of being overweight was
positively correlated with such membership (1.1). CONCLUSIONS: Both objective and
subjective assessments of weight are associated with the clustering of risky
sexual behaviors among adolescents, and these behavioral patterns differ by
gender.
PMID- 27608421
TI - Condition-dependent co-regulation of genomic clusters of virulence factors in the
grapevine trunk pathogen Neofusicoccum parvum.
AB - The ascomycete Neofusicoccum parvum, one of the causal agents of Botryosphaeria
dieback, is a destructive wood-infecting fungus and a serious threat to grape
production worldwide. The capability to colonize woody tissue, combined with the
secretion of phytotoxic compounds, is thought to underlie its pathogenicity and
virulence. Here, we describe the repertoire of virulence factors and their
transcriptional dynamics as the fungus feeds on different substrates and
colonizes the woody stem. We assembled and annotated a highly contiguous genome
using single-molecule real-time DNA sequencing. Transcriptome profiling by RNA
sequencing determined the genome-wide patterns of expression of virulence factors
both in vitro (potato dextrose agar or medium amended with grape wood as
substrate) and in planta. Pairwise statistical testing of differential
expression, followed by co-expression network analysis, revealed that physically
clustered genes coding for putative virulence functions were induced depending on
the substrate or stage of plant infection. Co-expressed gene clusters were
significantly enriched not only in genes associated with secondary metabolism,
but also in those associated with cell wall degradation, suggesting that dynamic
co-regulation of transcriptional networks contributes to multiple aspects of N.
parvum virulence. In most of the co-expressed clusters, all genes shared at least
a common motif in their promoter region, indicative of co-regulation by the same
transcription factor. Co-expression analysis also identified chromatin regulators
with correlated expression with inducible clusters of virulence factors,
suggesting a complex, multi-layered regulation of the virulence repertoire of N.
parvum.
PMID- 27608423
TI - Computational Study of the Palladium-Catalyzed Carbonylative Synthesis of
Aromatic Acid Chlorides: The Synergistic Effect of PtBu3 and CO on Reductive
Elimination.
AB - We describe herein computational studies on the unusual ability of Pd(PtBu3 )2 to
catalyze formation of highly reactive acid chlorides from aryl halides and carbon
monoxide. These show a synergistic role of carbon monoxide in concert with the
large cone angle PtBu3 that dramatically lowers the barrier to reductive
elimination. The tertiary structure of the phosphine is found to be critical in
allowing CO association and the generation of a high energy, four coordinate
(CO)(PR3 )Pd(COAr)Cl intermediate. The stability of this complex, and the barrier
to elimination, is highly dependent upon phosphine structure, with the tertiary
steric bulk of PtBu3 favoring product formation over other ligands. These data
suggest that even difficult reductive eliminations can be rapid with CO
association and ligand manipulation. This study also represents the first
detailed exploration of all the steps involved in palladium-catalyzed
carbonylation reactions with simple phosphine ligands, including the key rate
determining steps and palladium(0) catalyst resting state in carbonylations.
PMID- 27608422
TI - How functional disability relates to dentition in community-dwelling older adults
in Brazil.
AB - OBJECTIVE: To assess the association between dentition status and functional
disabilities among community-dwelling older individuals. SUBJECTS AND METHODS: A
total of 5012 individuals aged 65-74 were interviewed in 2013 during a nationwide
community-based survey. This cross-sectional study used a questionnaire including
information on dentition, locomotion impairment, difficulties in basic and
instrumental activities of daily life, socio-demographic characteristics,
behaviour and general health status. Poisson regression models assessed
prevalence ratios (PR) and 95% confidence intervals (95% CI). RESULTS: About
31.3% of older people in Brazil reported having >=21 preserved teeth, the
condition for a functional dentition without prosthetic appliances. This
proportion was significantly lower among individuals with locomotion impairment
and difficulties in basic and instrumental activities of daily life. After
adjusting for relevant covariates, functional dentition remained statistically
associated with severe (PR = 0.69, 95% CI = 0.15-0.63) and total (PR = 0.69, 95%
CI = 0.26-0.44) locomotion impairments, and difficulties in basic activities of
daily life (PR = 0.70, 95% CI = 0.53-0.93). CONCLUSION: Having a functional
dentition was significantly less prevalent among those affected by functional
disabilities, and this association is unlikely to be due to insufficient control
for relevant covariates. The association between dentition and functional
disability is bidirectional and involves a complex interplay of one upon the
other, and of factors that influence both outcomes.
PMID- 27608424
TI - Raman spectroscopic investigation on the molecular structure of apatite and
collagen in osteoporotic cortical bone.
AB - This study employed highly spectrally resolved Raman spectroscopy to examine the
molecular composition of cortical bone tissue obtained from murine females in
their healthy and ovariectomy- (OVX-) induced osteoporotic states. The aim of the
study was to identify structural differences at the molecular scale both in
apatite mineral and collagen fibrils between the two groups of samples. Raman
spectroscopy was used to determine the chemical composition of cortical bone in
regions including characteristic bands of both bone mineral and bone matrix. The
results demonstrated that the mineral apatite of bone did not undergo significant
amorphization in its diseased state, with the Raman microprobe also failing in
recognizing a direct role of carbonate content in the embrittlement of OVX
diseased bone. On the other hand, complex off-stoichiometry variations could be
detected in the columnar Ca-structure of the bony hydroxyapatite according to
morphological variations of the Raman band belonging to the symmetric phosphate
stretching (A1) band at ~959cm-1. A fundamental role was also recognized for
collagen quality on the process of bone embrittlement. The so-called matrix
maturity ratio, as systematically measured on Raman spectra in the Amide I
region, increased with statistical significance in OVX-treated samples as
compared to control samples. An 8% increase could be associated to a 115%
increase in elastic stress intensification in the mineral phase of OVX-diseased
tissue as compared to the control one, thus proving a degradation in the
(elastic) energy-dissipative capacity of a diseased bone matrix.
PMID- 27608425
TI - The coefficient of friction of UHMWPE along an entire walking cycle using a ball
on-disc tribometer under arthrokinematics and loading conditions prescribed by
ISO 14243-3:2014.
AB - The observation of tribological phenomena occurring in total knee replacement
(TKR) simulators may be obscured by the intrinsic complexity of their operation:
the dynamics and kinematics prescribed by the ISO 14243-3:2014 standard, and the
geometry of the surfaces involved. On the other hand, evaluating the individual
performance of the tribosystem elements may be carried out in simpler
apparatuses. An experimental method is presented here, by means of which the
arthrokinematics and loading conditions prescribed by the said standard are
adapted to a ball-on-disc configuration in order to observe the behavior of the
coefficient of friction along an entire walking cycle, using the contact point of
an AISI 316L stainless steel ball rolling/sliding on an ultra-high molecular
weight polyethylene (UHMWPE) disc, lubricated by a solution of fetal bovine
serum, at 37 degrees C. The method was tried on two different testing fluids
prepared with protein concentrations of 20g/L, according to the said standard,
and 36g/L, as received. The statistical model obtained for the behavior of the
COF during the entire walking cycle may be used in numerical simulations of
UHMWPE wear, under the conditions established by ISO 14243-3:2014.
PMID- 27608426
TI - Designing of silk and ZnO based antibacterial and noncytotoxic bionanocomposite
films and study of their mechanical and UV absorption behavior.
AB - Bionanocomposites of sericin and polyvinyl alcohol (PVA) were prepared by
solution casting method and zinc oxide nanoparticles were impregnated within the
polymer blend matrix through homogenous phase reaction between zinc chloride and
sodium hydroxide at high temperature following an ex-situ co-precipitation
method. The prepared bionanocomposites were characterized using Fourier Transform
Infrared Spectroscopy, X-ray diffraction, Field Emission Scanning Electron
Microscopy, Transmission Electron Microscopy and Atomic Force Microscopy
techniques. The presence of characteristic groups of sericin and ZnO
nanoparticles was ascertained by the FTIR spectra. XRD analysis confirmed the
impregnation of ZnO nanoparticles and sericin within the PVA matrix. XRD and
FESEM of the bionanocomposites provided information about their semicrystalline
nature, crystallite size of the particles, and irregular rough surfaces. The TEM
confirmed the size of ZnO particles to be in the nanometer range. AFM confirmed
the platykurtic nature of the surface while the negative surface skewness shows
the predominance of valleys over peaks suggesting for the planar nature of the
surface of the bionanocomposites. UV absorption properties of bionanocomposite
films were determined by UV absorption spectroscopy. UV absorption increased with
increasing amount of ZnO nanoparticles in the nanocomposites. Sericin was found
to absorb UV-C radiations between 200-290nm which is mainly due to aromatic amino
acids like tryptophan, tyrosine and phenylalanine. The ZnO nanoparticles and
sericin protein showed antimicrobial properties as evident from the inhibition
zones obtained against Staphylococcus aureus and Escherichia coli. The
bionanocomposite was found to be noncytotoxic which was proved by in vitro
cytotoxicity test. Microhardness of bionanocomposite films increased with
increase in the amount of ZnO nanoparticles in the sericin and PVA matrix.
PMID- 27608427
TI - Association between prenatal exposure to perfluorinated compounds and symptoms of
infections at age 1-4years among 359 children in the Odense Child Cohort.
AB - INTRODUCTION: Perfluorinated alkylated substances (PFAS) are persistent
industrial chemicals that have resulted in global environmental exposures.
Previous epidemiological studies have reported possible effects on the immune
system after developmental PFAS exposure, but the possible impact on childhood
infectious disease is unclear. OBJECTIVES: To investigate the association between
prenatal exposure to PFAS and symptoms of infections at age 1-4years. METHODS:
The Odense Child Cohort is an on-going prospective study on children's health,
where serum concentrations of perfluorooctane sulfonic acid (PFOS),
perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS),
perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in
649 pregnant women before gestational week 16. Of these women, 359 reported on
symptoms of infection in their child every two weeks for a one-year period. The
association between prenatal exposure to PFAS and the symptoms was estimated
using a logistic regression model and a negative binomial regression model. For
the latter, the outcome was reported as an incidence rate-ratio (IRR), and all
models were adjusted for maternal age, educational level, parity and child age.
RESULTS: On average, the children experienced symptoms of infection 23% of the
time during one year. PFOS exposure in the high tertile compared to the low
tertile was associated with a statistically significant increased proportion of
days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), P-trend<0.001) and an increased
odds of experiencing days with fever above the median (OR: 2.35 (95% CI: 1.31,
4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95% CI: 1.07,
3.62). Further, higher concentrations of PFOS and PFOA tended to increase the
number of episodes of co-occurrence of fever and coughing and fever and nasal
discharge during the one-year study period. CONCLUSION: We found a positive
association between prenatal exposure to PFOS and PFOA and the prevalence of
fever, which may be a sensitive marker of infection. This finding is in agreement
with an immunotoxic effect of prenatal exposure to PFAS. The wider implications
for childhood infectious disease deserve attention.
PMID- 27608428
TI - Measurement and health risk assessment of PM2.5, flame retardants, carbonyls and
black carbon in indoor and outdoor air in kindergartens in Hong Kong.
AB - Indoor air pollution is closely related to children's health. Polybrominated
diphenyl ethers (PBDEs) and dechlorane plus (DP) transmitted through indoor PM2.5
and dust, along with carbonyl compounds and black carbon (BC) aerosol were
analysed in five Hong Kong kindergartens. The results showed that 60% of the
median PM2.5 levels (1.3*101 to 2.9*101MUg/m3 for indoor; 9.5 to 8.8*101MUg/m3
for outdoor) in the five kindergartens were higher than the guidelines set by the
World Health Organization (2.5*101MUg/m3). Indoor PM2.5 mass concentrations were
correlated with outdoor PM2.5 in four of the kindergartens. The PBDEs (0.10
0.64ng/m3 in PM2.5; 0.30-2.0*102ng/g in dust) and DP (0.05-0.10ng/m3 in PM2.5;
1.3-8.7ng/g in dust) were detected in 100% of the PM2.5 and dust samples. Fire
retardant levels in the air were not correlated with the levels of dust in this
study. The median BC concentrations varied by >7-fold from 8.8*102ng/m-3 to
6.7*103ng/m-3 and cooking events might have caused BC concentrations to rise both
indoors and outdoors. The total concentrations of 16 carbonyls ranged from
4.7*101MUg/m3 to 9.3*101MUg/m3 indoors and from 1.9*101MUg/m3 to 4.3*101MUg/m3
outdoors, whilst formaldehyde was the most abundant air carbonyl. Indoor carbonyl
concentrations were correlated with outdoor carbonyls in three kindergartens. The
health risk assessment showed that hazard indexes (HIs) HIs of non-cancer risks
from PBDEs and DPs were all lower than 0.08, whilst non-cancer HIs of carbonyl
compounds ranged from 0.77 to 1.85 indoors and from 0.50 to 0.97 outdoors. The
human intake of PBDEs and DP through inhalation of PM2.5 accounted for 78% to 92%
of the total intake. The cancer hazard quotients (HQs) of formaldehyde ranged
from 4.5E-05 to 2.1E-04 indoors and from 1.9E-05 to 6.2E-05 outdoors. In general,
the indoor air pollution in the five Hong Kong kindergartens might present
adverse effects to children, although different schools showed distinct pollution
levels, so indoor air quality might be improved through artificial measures. The
data will be useful to developing a feasible management protocol for indoor
environments.
PMID- 27608430
TI - Simulations of Polyelectrolyte Adsorption to a Dielectric Like-Charged Surface.
AB - We explore, using the recently developed efficient Monte Carlo simulation method,
the interaction of an anionic polyelectrolyte solution with a like-charged
dielectric surface. In addition to polyions, the solution also contains salt with
either monovalent, divalent, or trivalent counterions. In agreement with recent
experimental observations, we find that multivalent counterions can lead to
strong adsorption of polyions onto the surface. On the other hand, addition of a
1:1 electrolyte diminishes the adsorption induced by the multivalent counterions.
Dielectric discontinuity at the interface is found to play only a marginal role
in polyion adsorption.
PMID- 27608429
TI - Oral administration of an aqueous extract from the oyster mushroom Pleurotus
ostreatus enhances the immunonutritional recovery of malnourished mice.
AB - Mushroom nutriceutical components have lately attracted interest for developing
immunonutritional support. However, there is relatively little information
pertaining to the use of mushroom preparations for modulating the metabolic and
immunological disorders associated to malnutrition. This study was aimed to
evaluate the effects of oral administration of an aqueous extract (CW-P) from
Pleurotus ostreatus on the recovery of biochemical and immunological functions of
malnourished mice. 8-week old female BALB/c mice were starved for 3days and then
refed with commercial diet supplemented with or without CW-P (100mg/kg) for
8days. Regardless of the diet used during refeeding, animal body weights and
serum protein concentrations did not differ between groups. Oral treatment with
CW-P normalized haemoglobin levels, liver arginase and gut mucosal weight. CW-P
increased total liver proteins and also DNA and protein contents in gut mucosa.
Pleurotus extract provided benefits in terms of macrophages activation as well as
in haemopoiesis, as judged by the recovery of bone marrow cells and leukocyte
counts. Moreover, CW-P stimulated humoral immunity (T-dependent and T non
dependent antibodies responses) compared to non-supplemented mice. CW-P extract
from the oyster mushroom can be used to develop specific food or nutritional
supplement formulations with potential clinical applications in the
immunotherapy.
PMID- 27608431
TI - Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic
Tumors in Vivo.
AB - The development of tools for the early diagnosis of pancreatic adenocarcinoma is
an urgent need in order to increase treatment success rate and reduce patient
mortality. Here, we present a modular nanosystem platform integrating soft
nanoparticles with a targeting peptide and an active imaging agent for
diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on
poly(methacrylic acid) were prepared and functionalized with the somatostatin
analogue PTR86 as the targeting moiety, since somatostatin receptors are
overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by
chelation and allowed in vivo investigation of the pharmacokinetic properties of
the nanoparticles using single photon emission computerized tomography (SPECT).
The resulting engineered nanosystem was tested in a xenograph mouse model of
human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of
targeted SCPNs in the tumor is higher than that observed for nontargeted
nanoparticles due to improved retention in this tissue.
PMID- 27608432
TI - 2-Azetidinones: Synthesis and biological evaluation as potential anti-breast
cancer agents.
AB - A series of twenty-five 2-azitidinone (beta-lactam) derivatives were synthesized
and evaluated for anti-cancer properties against breast cancer, MCF-7 and MDA-MB
231. These beta-lactam derivatives depicted significant cytotoxicity in cancer
cell lines but not in normal human mammary epithelial cells, MEpiC.
Interestingly, derivatives of 2-bromo ethyl acrylonitrile (19w) exhibited -
potent anti-proliferative activity with IC50, 5.79 +/- 0.01 MUM in MCF-7 and 6.86
+/- 0.009 MUM in MDA-MB-231. In addition, an increased expression of pro
apoptotic genes (p53, Bax, Bid) as well as decreased mRNA expression of cyclins
D1, E and Cdk 2, 6 along with cell cycle arrest at G1 phase was observed. 19w
treatment has shown higher percentage of Annexin-positive cells indicating
induction of apoptosis. Further, docking studies confirmed an interaction between
19w and ATP-binding catalytic site of AKT1. Mechanistically, 19w depicted dose
dependent decrease in phosphorylation of AKT and GSK-3beta and significant
decrease in AKT kinase activity. In conclusion, beta-lactam derivative 19w is a
potential anti-breast cancer therapeutic candidate targeting cell survival
pathway (AKT/GSK3beta).
PMID- 27608433
TI - Hepatitis E in blood donors: investigation of the natural course of asymptomatic
infection, Germany, 2011.
AB - Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors
from various European countries, but the natural course is rarely specified.
Here, we compared the progression of HEV viraemia, serostatus and liver-specific
enzymes in 10 blood donors with clinically asymptomatic genotype 3 HEV infection,
measuring HEV RNA concentrations, plasma concentrations of alanine/aspartate
aminotransferase, glutamate dehydrogenase and bilirubin and anti-HEV IgA, IgM and
IgG antibodies. RNA concentrations ranged from 77.2 to 2.19*10(5) IU/mL, with
viraemia lasting from less than 10 to 52 days. Donors showed a typical
progression of a recent HEV infection but differed in the first detection of anti
HEV IgA, IgM and IgG and seropositivity of the antibody classes. The diagnostic
window between HEV RNA detection and first occurrence of anti-HEV antibodies
ranged from eight to 48 days, depending on the serological assay used. The
progression of laboratory parameters of asymptomatic HEV infection was largely
comparable to the progression of symptomatic HEV infection, but only four of 10
donors showed elevated liver-specific parameters. Our results help elucidate the
risk of transfusion-associated HEV infection and provide a basis for development
of screening strategies. The diagnostic window illustrates that infectious blood
donors can be efficiently identified only by RNA screening.
PMID- 27608434
TI - The cannabinoid CB2 receptor-specific agonist AM1241 increases pentylenetetrazole
induced seizure severity in Wistar rats.
AB - The potential efficacy of cannabinoid receptor ligands for the treatment of
epilepsy remains controversial; cannabis components that act via cannabinoid type
1 (CB1) receptors produce anticonvulsant effects in animal models despite
treatment with the CB receptor agonist reliably inducing convulsions in various
species. Moreover, the potential role of cannabinoid receptor type 2 (CB2) to
modulate seizures remains under-investigated. This study assessed the effects of
the selective CB2 receptor agonist, AM1241, on pentylenetetrazole (PTZ)-induced
seizures in rats. A stereotactically placed guide cannula was surgically
implanted into the right lateral ventricle in adult Wistar rats which, 5-6days
later, received an acute intracerebroventricular (i.c.v.) microinfusion of AM1241
(0.01, 1 or 10MUg/2MUl or vehicle) 5min before intraperitoneal (i.p.) injection
of PTZ (70mg/kg). Rats were observed for 30min and the seizure severity behavior
measured using a modified Racine's scale. Additional groups of rats were
pretreated with a single low dose of the selective CB2 receptor antagonist, AM630
(dose 1mg/kg; i.p.), or vehicle, 30min prior to i.c.v. microinfusion of AM1241
(1MUg/2MUl). AM1241 administration significantly increased tonic-clonic seizure
incidence and severity while also decreasing the onset of generalized seizures
(AM1241 1 and 10MUg/2MUl). Pretreatment with AM630 prevented the proconvulsant
effects of AM1241. This study shows, for the first time, that selective
activation of CB2 receptors can increase generalized seizure susceptibility and
suggests that pathological hyperexcitability phenomena can be differentially
regulated by targeting CB1 and CB2 receptors.
PMID- 27608436
TI - Reasons for prolonged length of stay in the epilepsy monitoring unit.
AB - Epilepsy monitoring unit (EMU) admissions are essential for the
classification/localization of epileptic seizures (ES) and psychogenic non
epileptic seizures (PNES). However, the duration of admissions is highly
variable. Accordingly, we evaluated the duration of 596 EMU admissions and
reasons for prolonged (>7 days) lengths of stay (LOS). The average LOS was longer
for patients diagnosed with ES (8.0 days, SD 4.1 days) than all others (6.0 days,
SD 3.9 days, p<0.001). Of the 596 admissions, 231 (38.8%) had prolonged LOS. The
most commonly reported reason for prolonged stay was need to record additional
seizures (33%). Other contributors included complications such as seizure
clusters (6.9%), status epilepticus (1.6%), test complications (3.7%),
psychiatric concerns (4.3%), and medication side effects (1.6%). Our results
suggest multiple factors produce prolonged LOS with no factor accounting for the
majority. Recording an insufficient number of all habitual seizures was the
leading cause, which was over twice the percentage of reported complications
(17.6%). However, being able to prolong admissions when necessary resulted in
only 14.9% of admissions being inconclusive, potentially justifying the extra
expense. Efforts to shorten LOS may be best directed at faster recording of
seizures, but this may increase LOS due to complications. Our results may be
helpful when assessing whether efforts to shorten LOS are useful in improving the
quality and cost of care.
PMID- 27608435
TI - Factors associated with quality of life in a low-income population with epilepsy.
AB - OBJECTIVE: Currently few studies describe the variables that impact quality of
life (QoL) in patients with epilepsy in low-income populations. The study aimed
to establish relationships between QoL scores obtained through the QOLIE-10
inventory and clinical variables in patients older than 18 years diagnosed with
epilepsy. METHODS: We conducted an observational, descriptive, and cross
sectional study. We conducted consecutive recruitment of the data for all
patients with an epilepsy diagnosis who were treated in the neurology department
of Kennedy Western Hospital located in Bogota, Colombia. The variables that were
statistically significant in the bivariate analysis were included in a multiple
linear regression model. RESULTS: 220 patients were evaluated. The 50th
percentile of the total score of the QOLIE-10 scale was 70 (95% CI: 67,5-75). The
demographic profile was characterized by low level of education, unemployment,
and single marital status. The variables included in the regression model that
significantly affected QoL were depression (p<0.001), severe daytime sleepiness
(p=0.030), structural/metabolic etiology of epilepsy (p=0.021), drug resistant
epilepsy (p=0.015), and epilepsy with undetermined antiepileptic drug response
(p=0.007). CONCLUSIONS: The QoL in patients with epilepsy from a low-economic
population is determined primarily by depression, severe daytime sleepiness,
etiology of epilepsy (structural/metabolic etiology), and the type of therapeutic
response to antiepileptic drugs (drug resistant epilepsy and undetermined
antiepileptic drug response). These data suggest the need to promote early
diagnosis and treatment of psychiatric comorbidities and sleep disorders, as well
as effective and timely therapeutic interventions to prevent drug resistance in
epilepsy.
PMID- 27608437
TI - Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily
generalized tonic-clonic seizures: Pooled results from three Phase III studies.
AB - PURPOSE: Secondarily generalized tonic-clonic seizures (SGTCS) are among the most
devastating types of seizures, contributing to increased morbidity and mortality.
Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle 2A
(SV2A), has been shown to be useful for the adjunctive treatment of focal
seizures. We sought to determine its specific efficacy in treating SGTCS.
METHODS: Data were pooled from three Phase III studies (NCT00490035; NCT00464269;
NCT01261325) of adults with focal seizures taking 1-2 antiepileptic drugs (AEDs)
who received placebo or BRV 50-200mg/day without titration over a 12-week
treatment period. We report efficacy and safety/tolerability data for the BRV
therapeutic dose range (50-200 mg/day) in patients with focal seizures including
baseline SGTCS. RESULTS: Patients (efficacy population, N=409) had been diagnosed
with epilepsy for a mean+/-standard deviation duration of 22.2+/-13.1years.
Baseline median SGTCS frequency was 3.0 per 28days. The majority (293, 71.6%) had
failed >=2 AEDs prior to study enrollment. The median percent reduction from
baseline in SGTCS frequency/28days was: placebo, 33.3%; BRV 50mg/day, 66.6%
(p<0.001); BRV 100mg/day, 61.2% (p=0.002); and BRV 200mg/day, 82.1% (p<0.001).
The >=50% responder rate for SGTCS was: placebo, 33.0%; BRV 50mg/day, 61.3%
(p=0.003); BRV 100mg/day, 55.0% (p<0.001); and BRV 200mg/day, 64.0% (p<0.001).
Freedom from SGTCS was achieved by: placebo, 14.8%; BRV 50mg/day, 22.6%; BRV
100mg/day, 31.0%; and BRV 200mg/day, 36.0% of patients. Time to first SGTCS
during the treatment period was longer in patients receiving BRV than placebo
(26days vs 8days, hazard ratio 0.55, p<0.001). In the SGTCS safety population
(N=487), treatment-emergent adverse events (TEAEs) were reported by 60.6% of
patients receiving placebo vs 65.0% of patients receiving BRV >=50mg/day. Serious
TEAEs were reported by 3.1% placebo vs 3.9% BRV >=50mg/day. Discontinuations due
to TEAEs were 3.9% placebo vs 6.3% BRV >=50mg/day. CONCLUSIONS: In patients with
drug-resistant focal seizures, adjunctive BRV is effective in reducing the
frequency of SGTCS. Almost one-third (30.4%) of patients were rendered completely
free of SGTCS during the 12-week treatment period when taking BRV >=50mg/day. BRV
was well tolerated, with a TEAE profile consistent with that of the overall study
population.
PMID- 27608438
TI - Mirror neuron activation as a function of explicit learning: changes in mu-event
related power after learning novel responses to ideomotor compatible, partially
compatible, and non-compatible stimuli.
AB - Questions regarding the malleability of the mirror neuron system (MNS) continue
to be debated. MNS activation has been reported when people observe another
person performing biological goal-directed behaviors, such as grasping a cup.
These findings support the importance of mapping goal-directed biological
behavior onto one's motor repertoire as a means of understanding the actions of
others. Still, other evidence supports the Associative Sequence Learning (ASL)
model which predicts that the MNS responds to a variety of stimuli after
sensorimotor learning, not simply biological behavior. MNS activity develops as a
consequence of developing stimulus-response associations between a stimulus and
its motor outcome. Findings from the ideomotor literature indicate that stimuli
that are more ideomotor compatible with a response are accompanied by an increase
in response activation compared to less compatible stimuli; however, non
compatible stimuli robustly activate a constituent response after sensorimotor
learning. Here, we measured changes in the mu-rhythm, an EEG marker thought to
index MNS activity, predicting that stimuli that differ along dimensions of
ideomotor compatibility should show changes in mirror neuron activation as
participants learn the respective stimulus-response associations. We observed
robust mu-suppression for ideomotor-compatible hand actions and partially
compatible dot animations prior to learning; however, compatible stimuli showed
greater mu-suppression than partially or non-compatible stimuli after explicit
learning. Additionally, non-compatible abstract stimuli exceeded baseline only
after participants explicitly learned the motor responses associated with the
stimuli. We conclude that the empirical differences between the biological and
ASL accounts of the MNS can be explained by Ideomotor Theory.
PMID- 27608439
TI - Highly Flexible Hybrid CMOS Inverter Based on Si Nanomembrane and Molybdenum
Disulfide.
AB - 2D semiconductor materials are being considered for next generation electronic
device application such as thin-film transistors and complementary metal-oxide
semiconductor (CMOS) circuit due to their unique structural and superior
electronics properties. Various approaches have already been taken to fabricate
2D complementary logics circuits. However, those CMOS devices mostly demonstrated
based on exfoliated 2D materials show the performance of a single device. In this
work, the design and fabrication of a complementary inverter is experimentally
reported, based on a chemical vapor deposition MoS2 n-type transistor and a Si
nanomembrane p-type transistor on the same substrate. The advantages offered by
such CMOS configuration allow to fabricate large area wafer scale integration of
high performance Si technology with transition-metal dichalcogenide materials.
The fabricated hetero-CMOS inverters which are composed of two isolated
transistors exhibit a novel high performance air-stable voltage transfer
characteristic with different supply voltages, with a maximum voltage gain of
~16, and sub-nano watt power consumption. Moreover, the logic gates have been
integrated on a plastic substrate and displayed reliable electrical properties
paving a realistic path for the fabrication of flexible/transparent CMOS circuits
in 2D electronics.
PMID- 27608440
TI - Shock, acute disseminated intravascular coagulation, and microvascular
thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb
necrosis: reply.
PMID- 27608441
TI - Expression of Six Proteins Causes Reprogramming of Porcine Fibroblasts Into
Induced Pluripotent Stem Cells With Both Active X Chromosomes.
AB - In this study, we created porcine-induced pluripotent stem (iPS) cells with the
expression of six reprogramming factors (Oct3/4, Klf4, Sox2, c-Myc, Lin28, and
Nanog). The resulting cells showed growth dependent on LIF (leukemia inhibitory
factor) and expression of multiple stem cell markers. Furthermore, the iPS cells
caused teratoma formation with three layers of differentiation and had both
active X chromosomes (XaXa). Our iPS cells satisfied the both of important
characteristics of stem cells: teratoma formation and activation of both X
chromosomes. Injection of these iPS cells into morula stage embryos showed that
these cells participate in the early stage of porcine embryogenesis. Furthermore,
the RNA-Seq analysis detected that expression levels of endogenous pluripotent
related genes, NANOG, SOX2, ZFP42, OCT3/4, ESRRB, and ERAS were much higher in
iPS with six factors than that with four reprogramming factors. We can conclude
that the expression of six reprogramming factors enables the creation of porcine
iPS cells, which is partially close to naive iPS state. J. Cell. Biochem. 118:
537-553, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27608442
TI - Temporal Dynamics Assessment of Spatial Overlap Pattern of Functional Brain
Networks Reveals Novel Functional Architecture of Cerebral Cortex.
AB - OBJECTIVE: Various studies in the brain mapping field have demonstrated that
there exist multiple concurrent functional networks that are spatially overlapped
and interacting with each other during specific task performance to jointly
realize the total brain function. Assessing such spatial overlap patterns of
functional networks (SOPFNs) based on functional magnetic resonance imaging
(fMRI) has thus received increasing interest for brain function studies. However,
there are still two crucial issues to be addressed. First, the SOPFNs are
assessed over the entire fMRI scan assuming the temporal stationarity, while
possibly time-dependent dynamics of the SOPFNs is not sufficiently explored.
Second, the SOPFNs are assessed within individual subjects, while group-wise
consistency of the SOPFNs is largely unknown. METHODS: To address the two issues,
we propose a novel computational framework of group-wise sparse representation of
whole-brain fMRI temporal segments to assess the temporal dynamic spatial
patterns of SOPFNs that are consistent across different subjects. RESULTS:
Experimental results based on the recently publicly released Human Connectome
Project grayordinate task fMRI data demonstrate that meaningful SOPFNs exhibiting
dynamic spatial patterns across different time periods are effectively and
robustly identified based on the reconstructed concurrent functional networks via
the proposed framework. Specifically, those SOPFNs locate significantly more on
gyral regions than on sulcal regions across different time periods. CONCLUSION:
These results reveal novel functional architecture of cortical gyri and sulci.
SIGNIFICANCE: Moreover, these results help better understand functional dynamics
mechanisms of cerebral cortex in the future.
PMID- 27608446
TI - In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact
Rat Model of Chronic Ischemic Heart Failure.
AB - OBJECTIVE: The objective of this study was to define the clinical relevance of in
vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart
failure (CHF). METHODS: Electrical activation sequences, voltage amplitudes, and
monophasic action potentials (MAPs) were recorded from adult male Sprague-Dawley
rats six weeks after left coronary artery ligation. Programmed electrical
stimulation (PES) sequences were developed to induce sustained ventricular
tachycardia (VT). The inducibility of sustained VT was defined by PES and the
recorded tissue MAPs. RESULTS: Rats in CHF were defined ( 0.05) by elevated left
ventricular (LV) end-diastolic pressure (5 +/- 1 versus 18 +/- 2 mmHg), decreased
LV + d P/dt (7496 +/- 225 versus 5502 [Formula: see text] s), LV - dP/dt (7723 +/
208 versus 3819 [Formula: see text]), LV ejection fraction (79 +/- 3 versus
[Formula: see text]), peak developed pressure (176 +/- 4 versus 145 +/- 9 mmHg),
and prolonged time constant of LV relaxation Tau (18 +/- 1 versus 29 +/- 2 ms).
The EP data showed decreased ( 0.05) electrogram amplitude in border and infarct
zones (Healthy zone (H): 8.7 +/- 2.1 mV, Border zone (B): 5.3 +/- 1.6 mV, and
Infarct zone (I): 2.3 +/- 1.2 mV), decreased MAP amplitude in the border zone (H:
[Formula: see text] 1.0 mV, B: 9.7 +/- 0.5 mV), and increased repolarization
heterogeneity in the border zone (H: 8.1 +/- 1.5 ms, B: 20.2 +/- 3.1 ms). With
PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14)
versus Sham (0/8). CONCLUSIONS: These EP studies establish a clinically relevant
protocol for studying genesis of VT in CHF. SIGNIFICANCE: The in vivo rat model
of CHF combined with EP analysis could be used to determine the arrhythmogenic
potential of new treatments for CHF.
PMID- 27608445
TI - Optical Detection of Ultrasound in Photoacoustic Imaging.
AB - OBJECTIVE: Photoacoustic (PA) imaging emerges as a unique tool to study
biological samples based on optical absorption contrast. In PA imaging,
piezoelectric transducers are commonly used to detect laser-induced ultrasonic
waves. However, they typically lack adequate broadband sensitivity at ultrasonic
frequency higher than 100 MHz, whereas their bulky size and optically opaque
nature cause technical difficulties in integrating PA imaging with conventional
optical imaging modalities. To overcome these limitations, optical methods of
ultrasound detection were developed and shown their unique applications in PA
imaging. METHODS: We provide an overview of recent technological advances in
optical methods of ultrasound detection and their applications in PA imaging. A
general theoretical framework describing sensitivity, bandwidth, and angular
responses of optical ultrasound detection is also introduced. RESULTS: Optical
methods of ultrasound detection can provide improved detection angle and
sensitivity over significantly extended bandwidth. In addition, its versatile
variants also offer additional advantages, such as device miniaturization,
optical transparency, mechanical flexibility, minimal electrical/mechanical
crosstalk, and potential noncontact PA imaging. CONCLUSION: The optical
ultrasound detection methods discussed in this review and their future evolution
may play an important role in PA imaging for biomedical study and clinical
diagnosis.
PMID- 27608447
TI - Task-Driven Dictionary Learning Based on Mutual Information for Medical Image
Classification.
AB - OBJECTIVE: We present a novel variant of the bag-of-visual-words (BoVW) method
for automated medical image classification. METHODS: Our approach improves the
BoVW model by learning a task-driven dictionary of the most relevant visual words
per task using a mutual information-based criterion. Additionally, we generate
relevance maps to visualize and localize the decision of the automatic
classification algorithm. These maps demonstrate how the algorithm works and show
the spatial layout of the most relevant words. RESULTS: We applied our algorithm
to three different tasks: chest x-ray pathology identification (of four
pathologies: cardiomegaly, enlarged mediastinum, right consolidation, and left
consolidation), liver lesion classification into four categories in computed
tomography (CT) images and benign/malignant clusters of microcalcifications (MCs)
classification in breast mammograms. Validation was conducted on three datasets:
443 chest x-rays, 118 portal phase CT images of liver lesions, and 260
mammography MCs. The proposed method improves the classical BoVW method for all
tested applications. For chest x-ray, area under curve of 0.876 was obtained for
enlarged mediastinum identification compared to 0.855 using classical BoVW (with
p-value 0.01). For MC classification, a significant improvement of 4% was
achieved using our new approach (with p-value = 0.03). For liver lesion
classification, an improvement of 6% in sensitivity and 2% in specificity were
obtained (with p-value 0.001). CONCLUSION: We demonstrated that classification
based on informative selected set of words results in significant improvement.
SIGNIFICANCE: Our new BoVW approach shows promising results in clinically
important domains. Additionally, it can discover relevant parts of images for the
task at hand without explicit annotations for training data. This can provide
computer-aided support for medical experts in challenging image analysis tasks.
PMID- 27608448
TI - Oxygen Availability and Metabolic Dynamics During Mycobacterium tuberculosis
Latency.
AB - OBJECTIVE: In vitro models of Mycobacterium tuberculosis (Mtb) nonreplicating
persistence (NRP) suggest the rate of oxygen ( O2 ) depletion is a significant
determinant in persistence. However, few studies have characterized the metabolic
association between slow and rapid O2 depletion rates and successful versus
failed persistence. METHODS: We developed a theoretical model of Mtb metabolic
adaptation that includes O2 driven genetic modulation of enzymes in the
tricarboxylic acid cycle, energy, and redox recycling pathways. We conducted an
in silico study of Mtb adaptation, and investigated the metabolic dynamics that
enable persistence during slow versus rapid anaerobiosis. RESULTS: Consistent
with in vitro studies, during rapid anaerobiosis the most significant enzymatic
changes occurred during the active growth period while the majority of the slow
anaerobic system's adaptive response occurred during the first phase of aerobic
shiftdown (NRP1). The characteristic response of the two conditions differed,
with the slow anaerobic system exhibiting positive adaptation response,
upregulating six enzymes during NRP1, while the rapid system exhibited a negative
adaptation response, decreasing the levels of seven enzymes during active growth.
CONCLUSION: Results of our study illustrate the intricate metabolic balance Mtb
achieves during adaptation to anaerobic conditions, and how failure in redox
recycling correlates to failure in persistence. SIGNIFICANCE: We have provided
the first theoretical description of the genetic and metabolic death profile for
Mtb during anaerobic growth. Insight into Mtbs dynamic adaptation response
provides a unique systems framework for the development of targeted therapies to
reduce the likelihood of mycobacterial persistence and the related incidence of
latent tuberculosis infection.
PMID- 27608449
TI - Long-Term Recurrent Convolutional Networks for Visual Recognition and
Description.
AB - Models based on deep convolutional networks have dominated recent image
interpretation tasks; we investigate whether models which are also recurrent are
effective for tasks involving sequences, visual and otherwise. We describe a
class of recurrent convolutional architectures which is end-to-end trainable and
suitable for large-scale visual understanding tasks, and demonstrate the value of
these models for activity recognition, image captioning, and video description.
In contrast to previous models which assume a fixed visual representation or
perform simple temporal averaging for sequential processing, recurrent
convolutional models are "doubly deep" in that they learn compositional
representations in space and time. Learning long-term dependencies is possible
when nonlinearities are incorporated into the network state updates.
Differentiable recurrent models are appealing in that they can directly map
variable-length inputs (e.g., videos) to variable-length outputs (e.g., natural
language text) and can model complex temporal dynamics; yet they can be optimized
with backpropagation. Our recurrent sequence models are directly connected to
modern visual convolutional network models and can be jointly trained to learn
temporal dynamics and convolutional perceptual representations. Our results show
that such models have distinct advantages over state-of-the-art models for
recognition or generation which are separately defined or optimized.
PMID- 27608451
TI - Social Collaborative Filtering by Trust.
AB - Recommender systems are used to accurately and actively provide users with
potentially interesting information or services. Collaborative filtering is a
widely adopted approach to recommendation, but sparse data and cold-start users
are often barriers to providing high quality recommendations. To address such
issues, we propose a novel method that works to improve the performance of
collaborative filtering recommendations by integrating sparse rating data given
by users and sparse social trust network among these same users. This is a model
based method that adopts matrix factorization technique that maps users into low
dimensional latent feature spaces in terms of their trust relationship, and aims
to more accurately reflect the users reciprocal influence on the formation of
their own opinions and to learn better preferential patterns of users for high
quality recommendations. We use four large-scale datasets to show that the
proposed method performs much better, especially for cold start users, than state
of-the-art recommendation algorithms for social collaborative filtering based on
trust.
PMID- 27608452
TI - Characterizing and Discovering Spatiotemporal Social Contact Patterns for
Healthcare.
AB - During an epidemic, the spatial, temporal and demographic patterns of disease
transmission are determined by multiple factors. In addition to the physiological
properties of the pathogens and hosts, the social contact of the host population,
which characterizes the reciprocal exposures of individuals to infection
according to their demographic structure and various social activities, are also
pivotal to understanding and predicting the prevalence of infectious diseases.
How social contact is measured will affect the extent to which we can forecast
the dynamics of infections in the real world. Most current work focuses on
modeling the spatial patterns of static social contact. In this work, we use a
novel perspective to address the problem of how to characterize and measure
dynamic social contact during an epidemic. We propose an epidemic-model-based
tensor deconvolution framework in which the spatiotemporal patterns of social
contact are represented by the factors of the tensors. These factors can be
discovered using a tensor deconvolution procedure with the integration of
epidemic models based on rich types of data, mainly heterogeneous outbreak
surveillance data, socio-demographic census data and physiological data from
medical reports. Using reproduction models that include SIR/SIS/SEIR/SEIS models
as case studies, the efficacy and applications of the proposed framework are
theoretically analyzed, empirically validated and demonstrated through a set of
rigorous experiments using both synthetic and real-world data.
PMID- 27608455
TI - Ultrasound Small Vessel Imaging With Block-Wise Adaptive Local Clutter Filtering.
AB - Robust clutter filtering is essential for ultrasound small vessel imaging. Eigen
based clutter filtering techniques have recently shown great improvement in
clutter rejection over conventional clutter filters in small animals. However,
for in vivo human imaging, eigen-based clutter filtering can be challenging due
to the complex spatially-varying tissue and noise characteristics. To address
this challenge, we present a novel block-wise adaptive singular value
decomposition (SVD) based clutter filtering technique. The proposed method
divides the global plane wave data into overlapped local spatial segments, within
which tissue signals are assumed to be locally coherent and noise locally
stationary. This, in turn, enables effective separation of tissue, blood and
noise via SVD. For each block, the proposed method adaptively determines the
singular value cutoff thresholds based on local data statistics. Processing
results from each block are redundantly combined to improve both the signal-to
noise-ratio (SNR) and the contrast-to-noise-ratio (CNR) of the small vessel
perfusion image. Experimental results show that the proposed method achieved more
than two-fold increase in SNR and more than three-fold increase in CNR in dB
scale over the conventional global SVD filtering technique for an in vivo human
native kidney study. The proposed method also showed substantial improvement in
suppression of the depth-dependent background noise and better rejection of near
field tissue clutter. The effects of different processing block size and block
overlap percentage were systematically investigated as well as the tradeoff
between imaging quality and computational cost.
PMID- 27608454
TI - Gradient-Based Optimization for Poroelastic and Viscoelastic MR Elastography.
AB - We describe an efficient gradient computation for solving inverse problems
arising in magnetic resonance elastography (MRE). The algorithm can be considered
as a generalized 'adjoint method' based on a Lagrangian formulation. One
requirement for the classic adjoint method is assurance of the self-adjoint
property of the stiffness matrix in the elasticity problem. In this paper, we
show this property is no longer a necessary condition in our algorithm, but the
computational performance can be as efficient as the classic method, which
involves only two forward solutions and is independent of the number of
parameters to be estimated. The algorithm is developed and implemented in
material property reconstructions using poroelastic and viscoelastic modeling.
Various gradient- and Hessian-based optimization techniques have been tested on
simulation, phantom and in vivo brain data. The numerical results show the
feasibility and the efficiency of the proposed scheme for gradient calculation.
PMID- 27608458
TI - A Robust Approach for the Background Subtraction Based on Multi-Layered Self
Organizing Maps.
AB - Motion detection in video streams is a challenging task for several computer
vision applications. Indeed, segmentation of moving and static elements in the
scene allows to increase the efficiency of several challenging tasks, such as
human-computer interface, robot visions, and intelligent surveillance systems. In
this paper, we approach motion detection through a multi-layered artificial
neural network, which is able to build for each background pixel a multi-modal
color distribution evolving over time through self-organization. According to the
winner-take-all rule, each layer of the network models an independent state of
the background scene, in response to external disturbing conditions, such as
illumination variations, moving backgrounds, and jittering. As a result, our
background subtraction method exhibits high generalization capabilities that in
combination with a post-processing filtering schema allow to produce accurate
motion segmentation. Moreover, we propose an approach to detect anomalous events
(such as camera motion) that require background model re-initialization. We
describe our method in full details and we compare it against the most recent
background subtraction approaches. Experimental results for video sequences from
the 2012 and 2014 CVPR Change Detection data sets demonstrate how our methodology
outperforms many state-of-the-art methods in terms of detection rate.
PMID- 27608460
TI - The Bitonic Filter: Linear Filtering in an Edge-Preserving Morphological
Framework.
AB - A new filter is presented which has better edge and detail preserving properties
than a median, noise reduction capability similar to a Gaussian, and is
applicable to many signal and noise types. It is built on a definition of signal
as bitonic, i.e., containing only one local maxima or minima within the filter
range. This definition is based on data ranking rather than value; hence, the
bitonic filter comprises a combination of non-linear morphological and linear
operators. It has no data-level-sensitive parameters and can locally adapt to the
signal and noise levels in an image, precisely preserving both smooth and
discontinuous signals of any level when there is no noise, but also reducing
noise in other areas without creating additional artifactual noise. Both the
basis and the performance of the filter are examined in detail, and it is shown
to be a significant improvement on the Gaussian and median. It is also compared
over various noisy images to the image-guided filter, anisotropic diffusion, non
local means, the grain filter, and self-dual forms of leveling and rank filters.
In terms of signal-to-noise, the bitonic filter outperforms all these except non
local means, and sometimes anisotropic diffusion. However, it gives good visual
results in all circumstances, with characteristics which make it appropriate
particularly for signals or images with varying noise, or features at varying
levels. The bitonic has very few parameters, does not require optimization nor
prior knowledge of noise levels, does not have any problems with stability, and
is reasonably fast to implement. Despite its non-linearity, it hence represents a
very practical operation with general applicability.
PMID- 27608461
TI - Action Recognition in Still Images With Minimum Annotation Efforts.
AB - We focus on the problem of still image-based human action recognition, which
essentially involves making prediction by analyzing human poses and their
interaction with objects in the scene. Besides image-level action labels (e.g.,
riding, phoning), during both training and testing stages, existing works usually
require additional input of human bounding boxes to facilitate the
characterization of the underlying human-object interactions. We argue that this
additional input requirement might severely discourage potential applications and
is not very necessary. To this end, a systematic approach was developed in this
paper to address this challenging problem of minimum annotation efforts, i.e., to
perform recognition in the presence of only image-level action labels in the
training stage. Experimental results on three benchmark data sets demonstrate
that compared with the state-of-the-art methods that have privileged access to
additional human bounding-box annotations, our approach achieves comparable or
even superior recognition accuracy using only action annotations in training.
Interestingly, as a by-product in many cases, our approach is able to segment out
the precise regions of underlying human-object interactions.
PMID- 27608462
TI - Image Inpainting Through Metric Labeling via Guided Patch Mixing.
AB - In this paper, we present a novel formulation of exemplar-based image inpainting
as a metric labeling problem, and solve it through the simulated annealing
algorithm. Due to their greedy nature, exemplar-based methods sometimes produce
inpainted images, which are visually inconsistent. These methods are highly
dependent upon the initialization. To solve these problems, we generate five
images with a different initialization. A suitable mixture of these five images
produces a good inpainted image. The cost function of the proposed metric
labeling problem consists of three components, namely, neighbor cost, total
variation cost, and structure cost. A linear combination among these components
is used to maintain better visual consistency in the inpainted region having
smooth transition from the bordering regions of the source image. We use a
quality measure to this end. Our experiments on a wide variety of images
demonstrate that the proposed technique produces better inpainting images as
compared with some other state-of-the-art techniques.
PMID- 27608464
TI - Quaternion-Michelson Descriptor for Color Image Classification.
AB - In this paper, we develop a simple yet powerful framework called quaternion
Michelson descriptor (QMD) to extract local features for color image
classification. Unlike traditional local descriptors extracted directly from the
original (raw) image space, QMD is derived from the Michelson contrast law and
the quaternionic representation (QR) of color images. The Michelson contrast is a
stable measurement of image contents from the viewpoint of human perception,
while QR is able to handle all the color information of the image holisticly and
to preserve the interactions among different color channels. In this way, QMD
integrates both the merits of Michelson contrast and QR. Based on the QMD
framework, we further propose two novel quaternionic Michelson contrast binary
pattern descriptors from different perspectives. Experiments and comparisons on
different color image classification databases demonstrate that the proposed
framework and descriptors outperform several state-of-the-art methods.
PMID- 27608465
TI - Familiarity Vs Trust: A Comparative Study of Domain Scientists' Trust in Visual
Analytics and Conventional Analysis Methods.
AB - Combining interactive visualization with automated analytical methods like
statistics and data mining facilitates data-driven discovery. These visual
analytic methods are beginning to be instantiated within mixed-initiative
systems, where humans and machines collaboratively influence evidence-gathering
and decision-making. But an open research question is that, when domain experts
analyze their data, can they completely trust the outputs and operations on the
machine-side? Visualization potentially leads to a transparent analysis process,
but do domain experts always trust what they see? To address these questions, we
present results from the design and evaluation of a mixed-initiative, visual
analytics system for biologists, focusing on analyzing the relationships between
familiarity of an analysis medium and domain experts' trust. We propose a trust
augmented design of the visual analytics system, that explicitly takes into
account domain-specific tasks, conventions, and preferences. For evaluating the
system, we present the results of a controlled user study with 34 biologists
where we compare the variation of the level of trust across conventional and
visual analytic mediums and explore the influence of familiarity and task
complexity on trust. We find that despite being unfamiliar with a visual analytic
medium, scientists seem to have an average level of trust that is comparable with
the same in conventional analysis medium. In fact, for complex sense-making
tasks, we find that the visual analytic system is able to inspire greater trust
than other mediums. We summarize the implications of our findings with directions
for future research on trustworthiness of visual analytic systems.
PMID- 27608469
TI - Knot Optimization for Biharmonic B-splines on Manifold Triangle Meshes.
AB - Biharmonic B-splines, proposed by Feng and Warren, are an elegant generalization
of univariate B-splines to planar and curved domains with fully irregular knot
configuration. Despite the theoretic breakthrough, certain technical difficulties
are imperative, including the necessity of Voronoi tessellation, the lack of
analytical formulation of bases on general manifolds, expensive basis re
computation during knot refinement/removal, being applicable for simple domains
only (e.g., such as euclidean planes, spherical and cylindrical domains, and
tori). To ameliorate, this paper articulates a new biharmonic B-spline computing
paradigm with a simple formulation. We prove that biharmonic B-splines have an
equivalent representation, which is solely based on a linear combination of
Green's functions of the bi-Laplacian operator. Consequently, without explicitly
computing their bases, biharmonic B-splines can bypass the Voronoi partitioning
and the discretization of bi-Laplacian, enable the computational utilities on any
compact 2-manifold. The new representation also facilitates optimization-driven
knot selection for constructing biharmonic B-splines on manifold triangle meshes.
We develop algorithms for spline evaluation, data interpolation and hierarchical
data decomposition. Our results demonstrate that biharmonic B-splines, as a new
type of spline functions with theoretic and application appeal, afford
progressive update of fully irregular knots, free of singularity, without the
need of explicit parameterization, making it ideal for a host of graphics tasks
on manifolds.
PMID- 27608472
TI - Milk hypersensitivities: where is the grey line regarding their dietary
management?
AB - The proportion of people suffering or reporting to have a hypersensitivity caused
by cow's milk consumption is increasing, and even health professionals often face
difficulties into elaborating properly with a milk reaction due to misdiagnosis.
The scope of this review is to present literature data that lead into putting the
border line between cow's milk allergy and cow's milk intolerance, mainly
focusing on how the different pathophysiology leads to their different dietary
diagnosis and management.
PMID- 27608473
TI - Food allergy: practical approach on education and accidental exposure prevention.
AB - Food allergies are a growing problem and currently the primary treatment of food
allergy is avoidance of culprit foods. However, given the lack of information and
education and also the ubiquitous nature of allergens, accidental exposures to
food allergens are not uncommon. The fear of potential fatal reactions and the
need of a proper avoidance leads in most of the cases to the limitation of
leisure and social activities. This review aims to be a practical approach on
education and accidental exposure prevention regarding activities like shopping,
eating out, and travelling. The recommendations are focused especially on proper
reading of food labels and the management of the disease, namely in restaurants
and airplanes, concerning cross-contact and communication with other
stakeholders. The implementation of effective tools is essential to manage food
allergy outside home, avoid serious allergic reactions and minimize the disease's
impact on individuals' quality of life.
PMID- 27608474
TI - Probiotics and refractory chronic spontaneous urticaria.
AB - Background. In chronic spontaneous urticaria (CSU) first-line therapy with an
antihistamine-based regimen may not achieve satisfactory control in patients.
Thus, a continuing need exists for effective and safe treatments for refractory
CSU. Aim. To evaluate the clinical efficacy and safety of an intake of a
combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium
breve BR03) in patients with CSU who remain symptomatic despite concomitant H1
antihistamine therapy. Methods. This report analyzes the effects of therapy with
two probiotic strains on the clinical progress of 52 unselected patients with
difficulty to treat CSU underwent to medical examination in two Italian
specialist urticaria Clinics between September 2013 and September 2014. A mixture
of Lactobacillus LS01 and Bifidobacterium BR03 were administered in each patient
twice daily for 8 weeks. To evaluate patients' improvement with probiotics,
urticaria activity score over 7 days (UAS7) was used at baseline and at week 8 in
addition to a 5-question urticaria quality of life questionnaire. Results. Fifty
two patients with CSU were included in this study (10 male and 42 female, age
range 19-72 years). Mean disease duration was 1.5 years. Fourteen patients
discontinued treatment, so evaluable population consisted of 38 patients. Nine of
the 38 patients experienced mild clinical improvement during probiotic treatment
(23.7%); one patient reported significant clinical improvement (2.6%) and one
patient had complete remission of urticaria (2.6%). Twenty-seven patients did not
have improvement in symptoms (71.1%). No side effects during the course of
therapy were reported. Conclusions. A combination of Lactobacillus salivarius
LS01 and Bifidobacterium breve BR03 administered twice daily for 8 weeks might
reduce the symptoms scores and improve quality of life scores in a part of
patients with CSU who remained symptomatic despite treatment with H1
antihistamine mostly in subjects with allergic rhinitis.
PMID- 27608475
TI - Satisfaction and perceived effectiveness in patients on subcutaneous
immunotherapy with a high-dose hypoallergenic pollen extract.
AB - This study was designed to determine the level of satisfaction, tolerance and
perceived effectiveness by patients in the first pollen season after starting
treatment with Alergovit((r)). For this purpose, a nationwide, retrospective,
multicentre and cross-sectional observational study was carried on 256 patients.
Perceived effectiveness by the patients was measured using a visual analogue
scale and was clinically significant in 92.4% of the patients. The satisfaction
level was evaluated with a specific questionnaire. 32.5% of the patients were
totally satisfied with Allergovit((r)) and 48.8% reported a high degree of
satisfaction. The treatment was well tolerated by 99.2% of the patients. Our
results demonstrate that subcutaneous immunotherapy with Allergovit((r)) is
effective and well-tolerated in routine clinical practice.
PMID- 27608476
TI - Hyper IgM Syndrome with low IgM and thrombocytosis: an unusual case of
immunodeficiency.
AB - We report a 5 years old male child with low serum IgG, IgA and IgM levels, who
presented with recurrent perianal and oral ulcers, intermittent fever, and
protracted diarrhea. Despite the lack of typical respiratory symptoms, low serum
IgM level and persistent thrombocytosis, an X-linked hyper-IgM syndrome (X-HIGM)
was considered. Laboratory investigations revealed a diagnosis of hyper-IgM
syndrome caused by CD40L deficiency.
PMID- 27608478
TI - Clinical and radiological signs of ABPA associated with airways infection with
Aspergillus in the absence of specific IgE.
AB - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to
Aspergillus that mainly affects patients with asthma. For diagnosis, elevated
serum IgE level are needed according to Greenberger and Patterson criteria. We
report a case of 43 years-old woman who developed ABPA with productive cough,
fever and radiological findings of multiple confluent areas of consolidation in
both upper lobes. Laboratory tests showed elevated peripheral eosinophil counts
(9.3 x 10(3)/ml). In bronchial washing A. galactomannans and A. Fumigatus were
isolated, although we found normal levels of serum IgE, and the absence of serum
IgG and IgE antibodies to Aspergillus and A. galactomannans. In conclusion,
clinical and radiological signs of ABPA can be associated with Aspergillus
infection also in the absence of a specific serum antibody reaction.
PMID- 27608477
TI - Early onset steroid induced posterior subcapsular cataract in a patient with
common variable immunodeficiency: case reports and review of literature.
AB - Purpose. To report early onset steroid induced posterior subcapsular cataract in
a case of common variable immunodeficiency. Methods. Case report. Results. Here
we report a 14-yearold male of steroid induced bilateral posterior subcapsular
cataract in a common variable immunodeficiency patient with damaging mutations in
Glutathione reductase gene, leading to hypersensitivity of patient to
glucocorticoid (GC) products. Conclusions. In order to reduce the ocular side
effects of the GCs there are some advisements, including a complete history,
regular examination, GC should be prescribed in minimal dosage and minimal
course, and as possible GC-sparing drugs should always be considered.
PMID- 27608479
TI - Self-reported hair loss in patients with chronic spontaneous urticaria treated
with omalizumab: an under-reported, transient side effect?
AB - Omalizumab has been recently approved for treating patients with refractory to H1
antihistamines chronic spontaneous urticaria (CSU). Although hair loss is listed
among omalizumab side effects, there are no available data to estimate its
frequency. We describe for the first time hair loss as a side effect associated
with omalizumab administration in three women, 38, 62 and 70 years old, suffering
from refractory to H1-antihistamines CSU. This information was retrieved from
their Chronic Urticaria Quality of Life Questionnaires. Despite this side effect,
all patients agreed to continue omalizumab regular administration. Hair loss
appeared to be transient, lasting up to four months. All cases finally benefited
from omalizumab continuation.
PMID- 27608480
TI - A 1 MHz BW 34.2 fJ/step Continuous Time Delta Sigma Modulator With an Integrated
Mixer for Cardiac Ultrasound.
AB - Fully digitized 2D ultrasound transducer arrays require one ADC per channel with
a beamforming architecture consuming low power. We give design considerations for
per-channel digitization and beamforming, and present the design and measurements
of a continuous time delta-sigma modulator (CTDSM) for cardiac ultrasound
applications. By integrating a mixer into the modulator frontend, the phase and
frequency of the input signal can be shifted, thereby enabling both improved
conversion efficiency and narrowband beamforming. To minimize the power
consumption, we propose an optimization methodology using a simulated annealing
framework combined with a C++ simulator solving linear electrical networks. The
3rd order single-bit feedback type modulator, implemented in a 65 nm CMOS
process, achieves an SNR/SNDR of 67.8/67.4 dB across 1 MHz bandwidth consuming
131 [Formula: see text] of power. The achieved figure of merit of 34.2 fJ/step is
comparable with state-of-the-art feedforward type multi-bit designs. We further
demonstrate the influence to the dynamic range when performing dynamic receive
beamforming on recorded delta-sigma modulated bit-stream sequences.
PMID- 27608482
TI - Model-Driven Analysis of Eyeblink Classical Conditioning Reveals the Underlying
Structure of Cerebellar Plasticity and Neuronal Activity.
AB - The cerebellum plays a critical role in sensorimotor control. However, how the
specific circuits and plastic mechanisms of the cerebellum are engaged in closed
loop processing is still unclear. We developed an artificial sensorimotor control
system embedding a detailed spiking cerebellar microcircuit with three
bidirectional plasticity sites. This proved able to reproduce a cerebellar-driven
associative paradigm, the eyeblink classical conditioning (EBCC), in which a
precise time relationship between an unconditioned stimulus (US) and a
conditioned stimulus (CS) is established. We challenged the spiking model to fit
an experimental data set from human subjects. Two subsequent sessions of EBCC
acquisition and extinction were recorded and transcranial magnetic stimulation
(TMS) was applied on the cerebellum to alter circuit function and plasticity.
Evolutionary algorithms were used to find the near-optimal model parameters to
reproduce the behaviors of subjects in the different sessions of the protocol.
The main finding is that the optimized cerebellar model was able to learn to
anticipate (predict) conditioned responses with accurate timing and success rate,
demonstrating fast acquisition, memory stabilization, rapid extinction, and
faster reacquisition as in EBCC in humans. The firing of Purkinje cells (PCs) and
deep cerebellar nuclei (DCN) changed during learning under the control of
synaptic plasticity, which evolved at different rates, with a faster acquisition
in the cerebellar cortex than in DCN synapses. Eventually, a reduced PC activity
released DCN discharge just after the CS, precisely anticipating the US and
causing the eyeblink. Moreover, a specific alteration in cortical plasticity
explained the EBCC changes induced by cerebellar TMS in humans. In this paper,
for the first time, it is shown how closed-loop simulations, using detailed
cerebellar microcircuit models, can be successfully used to fit real experimental
data sets. Thus, the changes of the model parameters in the different sessions of
the protocol unveil how implicit microcircuit mechanisms can generate normal and
altered associative behaviors.The cerebellum plays a critical role in
sensorimotor control. However, how the specific circuits and plastic mechanisms
of the cerebellum are engaged in closed-loop processing is still unclear. We
developed an artificial sensorimotor control system embedding a detailed spiking
cerebellar microcircuit with three bidirectional plasticity sites. This proved
able to reproduce a cerebellar-driven associative paradigm, the eyeblink
classical conditioning (EBCC), in which a precise time relationship between an
unconditioned stimulus (US) and a conditioned stimulus (CS) is established. We
challenged the spiking model to fit an experimental data set from human subjects.
Two subsequent sessions of EBCC acquisition and extinction were recorded and
transcranial magnetic stimulation (TMS) was applied on the cerebellum to alter
circuit function and plasticity. Evolutionary algorithms were used to find the
near-optimal model parameters to reproduce the behaviors of subjects in the
different sessions of the protocol. The main finding is that the optimized
cerebellar model was able to learn to anticipate (predict) conditioned responses
with accurate timing and success rate, demonstrating fast acquisition, memory
stabilization, rapid extinction, and faster reacquisition as in EBCC in humans.
The firing of Purkinje cells (PCs) and deep cerebellar nuclei (DCN) changed
during learning under the control of synaptic plasticity, which evolved at
different rates, with a faster acquisition in the cerebellar cortex than in DCN
synapses. Eventually, a reduced PC activity released DCN discharge just after the
CS, precisely anticipating the US and causing the eyeblink. Moreover, a specific
alteration in cortical plasticity explained the EBCC changes induced by
cerebellar TMS in humans. In this paper, for the first time, it is shown how
closed-loop simulations, using detailed cerebellar microcircuit models, can be
successfully used to fit real experimental data sets. Thus, the changes of the
model parameters in the different sessions of the protocol unveil how implicit
microcircuit mechanisms can generate normal and altered associative behaviors.
PMID- 27608483
TI - Distributed Bounds on the Algebraic Connectivity of Graphs With Application to
Agent Networks.
AB - This paper establishes several bounds on the algebraic connectivity and spectral
radius of graphs. Before deriving these bounds, a directed graph with a leader
node is first investigated, for which some bounds on the spectral radius and the
smallest real part of all the eigenvalues of M = L + D are obtained using the
properties of M-matrix and non-negative matrix under a mild assumption, where L
is the Laplacian matrix of the graph and D = diag{d1, d2, ..., dN} with di > 0 if
node i can access the information of the leader node and 0 otherwise.
Subsequently, by virtue of the results on directed graphs, the bounds on the
algebraic connectivity and spectral radius of an undirected connected graph are
provided. Besides establishing these bounds, another important feature is that
all these bounds are distributed in the sense of only knowing the information of
edge weights' bounds and the number of nodes in a graph, without using any
information of inherent structures of the graph. Therefore, these bounds can be
in some sense applied to agent networks for reducing the conservatism where
control gains in control protocols depend on the eigenvalues of matrices M or L,
which are global information. Also some examples are provided for corroborating
the feasibility of the theoretical results.
PMID- 27608485
TI - Conflict of interest and bias in publication.
AB - In his excellent article about commercial conflict of interest, Mark Wilson
quotes Dennis Thompson, a political scientist who provided a searching analysis
of the concept of conflict of interest (Col). Using Thompson's analysis, Wilson
writes: "Determining whether factors such as ambition, the pursuit of fame and
financial gain had biased a judgment was challenging. Motives are not always
clear to either the conflicted party or to an outside observer." In this
commentary, I aim to broaden the discussion beyond the narrowly commercial
aspects of Col. I argue that bias can be introduced in major scientific journals
by the editors' choices and policies. The context is a controversy that erupted
in 2013 over the adequacy of informed consent in a clinical trial involving
extremely premature infants. In this, as in Wilson's example, the players
included the New England Journal of Medicine (NEJM), as well as the highest
officials of the US National Institutes of Health (NIH).
PMID- 27608487
TI - Vioxx redux - or how I learned to worry about industry-sponsored clinical trials.
AB - I read with interest Mark Wilson's recent article, "The New England Journal of
Medicine: commercial conflict of interest and revisiting the Vioxx scandal". I
believe this is an important contribution that underlines the aphorism "Those who
don't know history are doomed to repeat it." As Vioxx is a seminal example, it is
important to place it in its proper context, examining if this malfeasance
extends beyond the VIGOR study. While the epicentre of this conflict of interest
surely begins with the sponsor, I believe the following essay demonstrates that
this wave of egregiously unethical behaviour can exist and be propagated only
with the complicity of academic investigators, medical journals, a flawed peer
review system and an uncritical medical readership. Perhaps the most troubling is
that the factors that coalesced into the Vioxx scandal are, if anything, more
ubiquitous today, mandating increased vigilance to decrease the probability of
"getting fooled" again.
PMID- 27608486
TI - Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis
and growth.
AB - Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we
show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K
induced transformation and melanoma growth. IFI6 was transcriptionally
upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress
due to dysregulated DNA replication via E2F2. This stress consequentially
inhibited cellular transformation and melanoma growth via senescence or apoptosis
induction depending on the RB and p53 pathway status of the cells. NRAS-mutant
melanoma were significantly more resistant to the cytotoxic effects of DNA
replication stress-inducing drugs, and knockdown of IFI6 increased sensitivity to
these drugs. Pharmacological inhibition of IFI6 expression by the MEK inhibitor
trametinib, when combined with DNA replication stress-inducing drugs, blocked
NRAS-mutant melanoma growth. Collectively, we demonstrate that IFI6, via E2F2
regulates DNA replication and melanoma development and growth, and this pathway
can be pharmacologically targeted to inhibit NRAS-mutant melanoma.
PMID- 27608488
TI - Ethical erosion in newly qualified doctors: perceptions of empathy decline.
AB - OBJECTIVES: This study sought to understand whether UK Foundation doctors
perceived the phenomena of ethical erosion and empathy decline during their
initial period of clinical practice, and if so, why this occurred. METHODS: This
qualitative study used semi-structured interviews with nine doctors in their
first year of clinical practice at Royal Bolton Hospital, UK. Participants were
invited to discuss the definition of empathy, how individuals acquire and
maintain empathic ability, perceptions of ethical erosion in the self and others,
and how clinical experiences have influenced their empathic ability. The
interviews were transcribed, and analysed to identify emergent themes. RESULTS:
Each participant reported a conscious acknowledgement of empathy decline in their
own and their colleagues' early clinical experiences as doctors. Stressful
working environments, the prioritisation of patients' physical rather than
psychological well-being, and the attitudes of senior colleagues were all
suggested as possible causes. Some doctors believed that specialties with reduced
patient contact had a culture which precluded empathy, and influenced their own
practice. In addition, some described how their value judgements of patients had
affected their ability to empathise. However, all doctors perceived that empathy
skills were desirable in senior clinicians, and some believed that educational
interventions may be useful in arresting ethical erosion. CONCLUSIONS: Newly
qualified doctors are aware of ethical erosion in themselves and their colleagues
as they begin clinical practice. This has serious implications for patient care.
Improving working conditions may reverse this trend. Empathy skills training
within undergraduate and postgraduate curricula may be a useful intervention.
PMID- 27608490
TI - Team Communication: It's About Patient Safety.
PMID- 27608491
TI - Oncology Workforce Studies: Moving Beyond the Head Count.
PMID- 27608489
TI - Disruption of mechanical stress in extracellular matrix is related to Stanford
type A aortic dissection through down-regulation of Yes-associated protein.
AB - In this study, we assessed whether the down-regulation of Yes-associated protein
(YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical
stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples
were obtained from heart transplantation donors as normal controls and from STAAD
patients undergoing surgical replacement of the ascending aorta. Decreased
maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP
down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP
was down-regulated over time during the development of ECM damage, and increased
VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under
static conditions in vitro, and the change in mechanical stress induced YAP down
regulation and VSMC apoptosis. This study provides evidence that YAP down
regulation caused by the disruption of mechanical stress is associated with the
development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is
among the most elusive and life-threatening vascular diseases, better
understanding of the molecular pathogenesis of STAAD is critical to improve
clinical outcome.
PMID- 27608492
TI - Errata.
PMID- 27608495
TI - Palliative Radiation Therapy for the Hospice Patient: Nuances of Care and
Reimbursement.
PMID- 27608496
TI - Expanding the Scope of the National Practice Oncology Benchmark Would Be a
Critical Source for Understanding Outpatient Oncology Practice Costs and Profits
in a Time of Change.
PMID- 27608498
TI - Soft Material Approach to Induce Oxidative Stress in Mesenchymal Stem Cells for
Functional Tissue Repair.
AB - Biomimicking hydrogel-based cell culture platforms with physiologically relevant
stiffness are powerful tools to modulate the behaviors of stem cells. Herein, the
use of fibronectin-conjugated polyacrylamide (PAA) hydrogel biointerface is
exploited to modulate the intracellular oxidative stress of human bone marrow
derived mesenchymal stem cells (MSCs). We show that compliant culture surface
with kPa range matrix stiffness can augment the expression level of reactive
oxygen species (ROS) in MSCs by approximately 2-4 fold compared with cells grown
on conventional FN coated glass control surface in a noncytotoxic manner. Via an
unbiased proteomics approach and mechanistic studies, we show that the secretion
level of a sub series of "mechano-sensitive" chemokines and trophic factors is
heavily dependent on the PAA matrix stiffness mediated ROS level. Importantly,
the secretome harvested from the cells that were grown on the PAA hydrogel was
found to enhance wound healing in both in vitro and in vivo full thickness mouse
excisional wound model. The devised "soft approach" to induce oxidative stress in
MSCs is posited to pave the way for novel cell-free therapeutic interventions
targeting a wide variety of diseases and to foster functional tissue repair.
PMID- 27608499
TI - Biogas production from the mechanically pretreated, liquid fraction of sorted
organic municipal solid wastes.
AB - The high liquid content in fruit and vegetable wastes makes it convenient to
mechanically separate these wastes into mostly liquid and solid fractions by
means of pretreatment. Then, the liquid fraction can be treated using a high-rate
anaerobic biofilm reactor to produce biogas, simultaneously reducing the amount
of solids that must be landfilled. In this work, the specific composition of
municipal solid waste (MSW) in a public market was determined; then, the sorted
organic fraction of municipal solid waste was treated mechanically to separate
and characterize the mostly liquid and solid fractions. Then, the mesophilic
anaerobic digestion for biogas production of the first fraction was evaluated.
The anaerobic digestion resulted in a reduced hydraulic retention time of two
days with high removal of chemical oxygen demand, that is, 88% on average, with
the additional benefit of reducing the mass of the solids that had to be
landfilled by about 80%.
PMID- 27608500
TI - Extended high frequency audiometry can diagnose sub-clinic involvement in a
seemingly normal hearing systemic lupus erythematosus population.
AB - CONCLUSIONS: Sensorineural hearing loss must be considered within the clinical
picture of systemic lupus erythematosus. The results confirm the usefulness of
extended high-frequency audiometry in the audiologic testing of these patients,
enabling the possibility of modifying or applying a preventive treatment for a
possible hearing loss. OBJECTIVES: Hearing involvement is usually under-diagnosed
with routine auditory examination. This study proposes the use of extended high
frequency audiometry to achieve a correct detection of a possible asymptomatic
hypoacusis in early stages of the disease. The aim of this study is to analyze
the hearing levels in extended high-frequencies in these patients and to
correlate the hearing loss with the severity of the disease and the immunological
parameters. METHODS: A descriptive cross-sectional study was performed. Fifty
five patients with systemic lupus erythematosus were included in the study. The
control group consisted of 71 patients paired by age and sex with the study
population. Both a pure tone audiometry and an extended high-frequency audiometry
(8-18 KHz) were performed. RESULTS: In total, 70% were diagnosed with
sensorineural hearing loss with extended high-frequency audiometry, overcoming
the results obtained with pure tone audiometry (30.9%). Statistically significant
correlations were found within the patients regarding sensorineural hearing loss
related with age, disease activity and cryoglobulinemia.
PMID- 27608497
TI - Pericyte-fibroblast transition promotes tumor growth and metastasis.
AB - Vascular pericytes, an important cellular component in the tumor
microenvironment, are often associated with tumor vasculatures, and their
functions in cancer invasion and metastasis are poorly understood. Here we show
that PDGF-BB induces pericyte-fibroblast transition (PFT), which significantly
contributes to tumor invasion and metastasis. Gain- and loss-of-function
experiments demonstrate that PDGF-BB-PDGFRbeta signaling promotes PFT both in
vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF
BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological
inhibition and genetic deletion of PDGFRbeta ablate the PDGF-BB-induced PFT.
Genetic tracing of pericytes with two independent mouse strains, TN-AP
CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain
stromal fibroblast and myofibroblast markers in tumors. Importantly,
coimplantation of PFT cells with less-invasive tumor cells in mice markedly
promotes tumor dissemination and invasion, leading to an increased number of
circulating tumor cells and metastasis. Our findings reveal a mechanism of
vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing
PFT, and thus targeting PFT may offer a new treatment option of cancer
metastasis.
PMID- 27608501
TI - Living with HIV in West Bengal, India: perceptions of infected children and their
caregivers.
AB - Children living with HIV (CLH) face several physical and psychological
challenges. The impact of the disease is not limited to the affected CLH, but
also affects their caregivers and family members. We qualitatively explored the
experiences, knowledge, concerns, and perceptions of primary caregivers and
triangulated those aspects with those expressed by their CLH. We conducted 34 in
depth interviews (IDI) with primary caregivers of 8- to 15-year-old CLH residing
in West Bengal, India. Four focus group discussions (FGD) with CLH were held, two
each with children aged 8-12 and 13-15 years. Participants were recruited with
the help of a community-based organization providing need-based services to
adults and CLH. Five major themes shared by caregivers and children were
identified, including concerns about HIV, medications, discriminatory behaviors,
having a "healthy mind", and the advantages and limitations of available HIV
related health services. Two primary themes exclusively from IDI with caregivers
were caregiving challenges and concerns about the future of their CLH. Indian CLH
and their caregivers face many daily challenges, and there are many unmet but
relevant expectations. Caregiving goes beyond the child-caregiver dynamic, and is
intertwined with the local community and the healthcare and support system
structures. The current study underscores the need for comprehensive care
programs focusing on improving support to both CLH and caregivers.
PMID- 27608502
TI - Cellular immune responses induced in vitro by Ehrlichia ruminantium
secreted proteins and identification of vaccine candidate peptides.
AB - Secreted proteins are reported to induce cell-mediated immunity characterised by
the production of interferon-gamma (IFN)-gamma. In this study three open reading
frames (ORFs) (Erum8060, Erum7760, Erum5000) encoding secreted proteins were
selected from the Ehrlichia ruminantium (Welgevonden) genome sequence using
bioinformatics tools to determine whether they induce a cellular immune response
in vitro with mononuclear cells from needle and tick infected animals. The whole
recombinant protein of the three ORFs as well as four adjacent fragments of the
Erum5000 protein (Erum5000A, Erum5000B, Erum5000C, Erum5000D) were successfully
expressed in a bacterial expression system which was confirmed by immunoblots
using anti-His antibodies and sheep sera. These recombinant proteins were assayed
with immune sheep and cattle peripheral blood mononuclear cells (PBMCs), spleen
and lymph node (LN) cells to determine whether they induce recall cellular immune
responses in vitro. Significant proliferative responses and IFN-gamma production
were evident for all recombinant proteins, especially Erum5000A, in both ruminant
species tested. Thus overlapping peptides spanning Erum5000A were synthesised and
peptides that induce proliferation of memory CD4+ and CD8+ T cells and production
of IFN-gamma were identified. These results illustrate that a Th1 type immune
response was elicited and these recombinant proteins and peptides may therefore
be promising candidates for development of a heartwater vaccine.
PMID- 27608503
TI - A pathogen-specific approach towards udder health management in dairy herds:
Using culture and somatic cell counts from routine herd investigations.
AB - A dedicated udder health diagnostic programme was developed and used over a 15
year period in South Africa to analyse milk samples based on microbiological and
cytological patterns within various groups and for individual cows and udder
quarters in dairy herds. These pathogen-specific analyses are utilised for pro
active improvement and management of udder health in South African commercial
dairy herds. The programme acts as a monitoring tool and identifies management
areas at risk and individual cows with udder disease and uses both quarter and
composite milk samples. Intra-mammary infection (IMI) is a dynamic situation and
depending on the time a milk sample is taken, false-negative results may be
obtained. A new IMI and an infection that is curing may both have low somatic
cell counts (SCCs), masking the true bacterial status. SCC in individual infected
udder quarters may differ greatly depending on the causative bacterial species,
its pathogenicity, the host immune status and the environmental factors involved.
A pathogen-specific udder health approach was followed with repeated herd tests
to take account of these udder health dynamics. The results of the herd IMI
investigation are applied in practice to assist veterinarians, udder health
consultants and managers to make informed and specific detailed decisions at both
a herd and on an individual cow basis regarding udder health.
PMID- 27608504
TI - Effect of the infection with the nematode Haemonchus contortus
(Strongylida: Trichostrongylidae) on the haematological, biochemical, clinical
and reproductive traits in rams.
AB - This study aimed to investigate the effect of Haemonchus contortus infection on
rams' haematological, biochemical and clinical parameters and reproductive
performances. A total number of 12 Barbarine rams (control and infected) were
included in the experiment. The infected group received 30 000 H. contortus third
stage larvae orally. Each ram's ejaculate was immediately evaluated for volume,
sperm cell concentration and mortality rate. At the end of the experiment (day 82
post-infection), which lasted 89 days, serial blood samples were collected in
order to assess plasma testosterone and luteinising hormone (LH) concentrations.
There was an effect of time, infection and their interaction on haematological
parameters (p < 0.001). In infected rams, haematocrit, red blood cell count and
haemoglobin started to decrease from 21 days post-infection. There was an effect
of time and infection for albumin. For total protein, only infection had a
statistically significant effect. For glucose, only time had a statistically
significant effect. Concentrations were significantly lower in infected rams
compared to control animals. A significant effect of infection and time on sperm
concentrations and sperm mortality was observed. The effect of infection appears
in time for sperm concentrations at days 69 and 76 post-infection. Sperm
mortality rate was significantly higher in infected animals at day 46 post
infection when compared to control group (p < 0.05). Finally, plasma testosterone
traits (average concentration, cumulated levels during the sampling period and
pulse frequency) were depressed in infected rams when compared to control
counterparts; none of these endocrine traits were affected for plasma LH.
PMID- 27608505
TI - Comparison of nucleotide sequences of recent and previous lineages of peste-des
petits-ruminants viruses of sheep and goats in Nigeria.
AB - Peste-des-petits-ruminants virus (PPRV) is a highly contagious, fatal and
economically important viral disease of small ruminants that is still endemic and
militates against the production of sheep and goats in endemic areas of the
world. The aim of this study was to describe the viral strains within the
country. This was carried out by collecting tissue and swab samples from sheep
and goats in various agro-ecological zones of Nigeria. The phylogeny of archived
PPRV strains or isolates and those circulating and causing recent outbreaks was
determined by sequencing of the nucleoprotein (N)-gene. Twenty tissue and swab
samples from apparently healthy and sick sheep and goats were collected randomly
from 18 states, namely 3 states in each of the 6 agro-ecological zones visited. A
total of 360 samples were collected. A total of 35 samples of 360 (9.7%) tested
positive by reverse transcriptase-polymerase chain reaction, of which 25 were
from oculo-nasal swabs and 10 were from tissue samples. Neighbour-joining
phylogenetic analysis using Phylogenetic Analysis Using Parsimony (PAUP)
identified four different lineages, that is, lineages I, II, III and IV.
Interestingly, the Nigerian strains described in this study grouped in two
separate major lineages, that is, lineages II and IV. Strains from Sokoto, Oyo,
Plateau and Ondo states grouped according to the historical distribution of PPRV
together with the Nigerian 75/1 strain of lineage II, while other strains from
Sokoto, Oyo, Plateau, Akwa-Ibom, Adamawa, Kaduna, Lagos, Bauchi, Niger and Kano
states grouped together with the East African and Asian strains of lineage IV.
This finding confirms that both lineage II and IV strains of PPRV are circulating
in Nigeria. Previously, only strains of lineage II were found to be present in
the country.
PMID- 27608506
TI - Hemolytic crisis following acetaminophen overdose in a patient with G6PD
deficiency.
PMID- 27608507
TI - Does neuropsychological performance impact on real-life functional achievements
in obsessive-compulsive disorder? A preliminary study.
AB - OBJECTIVE: We investigated the association between neuropsychological performance
and real-life functioning in obsessive-compulsive disorder (OCD). As a secondary
aim, we investigated the association between neuropsychological performance and
self-reported quality of life (QoL). METHODS: We retrospectively selected 68 of
240 inpatients with OCD, who had been hospitalised for a 4-week psychiatric
rehabilitation programme. We used clinical information recorded in the patients'
electronic medical records. We considered the following variables:
neuropsychological performance (verbal/visual memory, sustained attention, visual
constructive ability, and language fluency; in a sub-sample of 37 subjects,
divided attention, working memory, and attentional shifting were also available);
real-life functional achievements (social/vocational outcomes and independent
living); subjectively reported QoL (WHOQOL-BREF); obsessive-compulsive (OC)
symptoms severity (DY-BOCS). RESULTS: We found significant associations between
poorer neuropsychological performance and poorer achievements in independent
living and vocational outcomes. Among the different neuropsychological tests, we
found significant associations between language fluency/executive processing and
independent living, and between divided attention, attentional shifting, working
memory and vocational outcome. We found no significant associations between
neuropsychological performance and subjectively reported QoL. OC symptoms
severity was not associated with real-life functional achievements. CONCLUSIONS:
Our preliminary results suggest that poorer neuropsychological performance may be
associated with impaired real-life functioning in subjects with OCD.
PMID- 27608508
TI - Swimming Microrobot Optical Nanoscopy.
AB - Optical imaging plays a fundamental role in science and technology but is limited
by the ability of lenses to resolve small features below the fundamental
diffraction limit. A variety of nanophotonic devices, such as metamaterial
superlenses and hyperlenses, as well as microsphere lenses, have been proposed
recently for subdiffraction imaging. The implementation of these
micro/nanostructured lenses as practical and efficient imaging approaches
requires locomotive capabilities to probe specific sites and scan large areas.
However, directed motion of nanoscale objects in liquids must overcome low
Reynolds number viscous flow and Brownian fluctuations, which impede stable and
controllable scanning. Here we introduce a new imaging method, named swimming
microrobot optical nanoscopy, based on untethered chemically powered microrobots
as autonomous probes for subdiffraction optical scanning and imaging. The
microrobots are made of high-refractive-index microsphere lenses and powered by
local catalytic reactions to swim and scan over the sample surface. Autonomous
motion and magnetic guidance of microrobots enable large-area, parallel and
nondestructive scanning with subdiffraction resolution, as illustrated using soft
biological samples such as neuron axons, protein microtubulin, and DNA nanotubes.
Incorporating such imaging capacities in emerging nanorobotics technology
represents a major step toward ubiquitous nanoscopy and smart nanorobots for
spectroscopy and imaging.
PMID- 27608509
TI - Quercetin derivatives as non-nucleoside inhibitors for dengue polymerase:
molecular docking, molecular dynamics simulation, and binding free energy
calculation.
AB - Dengue is an important public health problem in tropical and subtropical regions
of the world. Neither vaccine nor an antiviral medication is available to treat
dengue. This insists the need of drug discovery for dengue. In order to find a
potent lead molecule, RNA-dependent RNA polymerase which is essential for dengue
viral replication is chosen as a drug target. As Quercetin showed antiviral
activity against several viruses, quercetin derivatives developed by
combinatorial library synthesis and mined from PubChem databases were screened
for a potent anti-dengue viral agent. Our study predicted Quercetin 3-(6"-(E)-p
coumaroylsophoroside)-7-rhamnoside as a dengue polymerase inhibitor. The results
were validated by molecular dynamics simulation studies which reveal water
bridges and hydrogen bonds as major contributors for the stability of the
polymerase-lead complex. Interactions formed by this compound with residues
Trp795, Arg792 and Glu351 are found to be essential for the stability of the
polymerase-lead complex. Our study demonstrates Quercetin 3-(6"-(E)-p
coumaroylsophoroside)-7-rhamnoside as a potent non-nucleoside inhibitor for
dengue polymerase.
PMID- 27608510
TI - The Olympians of wound care.
PMID- 27608511
TI - Thermal territories of the abdomen after caesarean section birth: infrared
thermography and analysis.
AB - OBJECTIVE: To develop and refine qualitative mapping and quantitative analysis
techniques to define 'thermal territories' of the post-partum abdomen, the
caesarean section site and the infected surgical wound. In addition, to explore
women's perspectives on thermal imaging and acceptability as a method for
infection screening. METHOD: Prospective feasibility study undertaken at a large
University teaching hospital, Sheffield UK. Infrared thermal imaging of the
abdomen was undertaken at the bedside on the first two days after elective
caesarean section. Target recruitment: six women in each of three body mass index
(BMI) categories (normal, 18.5-24.9 kg/m2; overweight 25-29.9 kg/m2; obese >=30
kg/m2). Additionally, women presenting to the ward with wound infection were
eligible for inclusion in the study. Perspectives on the use of thermal imaging
and its practicality were also explored via semi-structured interviews and
analysed using thematic content analysis. RESULTS: We recruited 20 women who had
all undergone caesarean section. From the booking BMI, eight women were obese
(including two women with infected wounds), seven women were overweight and five
women had a normal BMI. Temperature (oC) profiling and pixel clustering
segmentation (hierarchical clustering-based segmentation, HCS) revealed
characteristic features of thermal territories between scar and adjacent regions.
Differences in scar thermal intensity profiles exist between healthy scars and
infected wounds; features that have potential for wound surveillance. The maximum
temperature differences (?T) between healthy skin and the wound site exceed 2o C
in women with established wound infection. At day two, two women had a scar
thermogram with features observed in the 'infected' wound thermogram. CONCLUSION:
Thermal imaging at early and later times after caesarean birth is feasible and
acceptable. Women reported potential benefits of the technique for future wound
infection screening. Thermal intensity profiling and HCS for pixel cluster
dissimilarity between scar and adjacent healthy skin has potential as a method
for the development of techniques targeted to early infection surveillance in
women after caesarean section.
PMID- 27608512
TI - Multinational, pilot audit of a Velcro adjustable compression wrap system for
venous and lymphatic conditions.
AB - OBJECTIVE: The aim of this small pilot audit was to record the performance of an
adjustable Velcro compression wrap, ReadyWrap, and the experiences of patients
and health-care professionals using the system as a self-care option for the
management of venous and lymphatic leg conditions in both the treatment and
maintenance phases. METHOD: This audit was held within a 4-week review period.
Participants included venous leg ulcer (VLU) patients with and without oedema,
and patients with lymphoedema. Where open wounds were present they were managed
with debridement, skin care and dressings according to clinical need. Lymphoedema
patients received manual lymphatic drainage and skin care regimens as per
standard practice. The Velcro system evaluated formed part of a treatment pathway
with compression bandages and/or compression hosiery as clinically indicated.
Patients, carers and health-care professionals applied the garments following
assessment and training. Objective data recorded included change in
circumferential measurements and improvement in wound status. Observation of
health-care professionals, patients and carers with regard to the comfort and
ease of application/removal of the device were recorded. RESULTS: There were 17
patients included in the audit. Within the 4-week period a reduction in limb
circumference was recorded in all cases. Improvements in open wounds were
recorded in most cases. Following the 4-week audit period 94% of the application
of the device was performed by either the patient (59%) or the carer (35%)
thereby reducing the health-care professional contact that was required for
application. CONCLUSION: Early results in this small audit demonstrate that this
adjustable Velcro compression wrap may provide a simple, clinically effective and
patient-acceptable solution for self-care with compression. Use of this type of
device could have the potential to reduce overall health-care burden by reducing
necessary skilled treatment visits and/or cost while still achieving good
clinical outcomes. Further studies are required to confirm this pilot study and
provide additional data.
PMID- 27608513
TI - Enhanced wound healing by topical application of ointment containing a low
concentration of povidone-iodine.
AB - OBJECTIVE: To investigate the effect of a novel topical wound-healing agent, low
concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum
rich base on skin-wound models in rats and rabbits. METHOD: The therapeutic
efficacy of topically applied LPIO was compared to that of standard-concentration
povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness
skin-wound model in 24 hairless rats and a full-thickness skin-defect model in
rabbit earlobes. The animals were kept under standardised conditions at the
Central Research Laboratory of Maruishi Pharmaceutical Co. Ltd. (Osaka, Japan).
Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as
well as histopathological and immuno-histochemical examinations. RESULTS: LPIO
enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and
inflammation, when compared with that in SPIO and non-treatment control. LPIO
also markedly improved wound healing in rabbit earlobe ulcers by significantly
improving re-epithelialisation, compared with that in SPIO. CONCLUSION: The
results of this study suggest that LPIO is a useful topical therapy for
ulcerative lesions.
PMID- 27608514
TI - Clinical evaluation of a dressing with poly absorbent fibres and a silver matrix
for managing chronic wounds at risk of infection: a non comparative trial.
AB - OBJECTIVE: To assess the efficacy, safety and acceptability of a new silver poly
absorbent dressing (UrgoCleanAg) in the local management of exudative chronic
wounds at risk of infection, with inflammatory signs suggesting heavy bacterial
load. METHOD: This prospective, multicentre, non-comparative clinical trial was
conducted in French hospital wards (dermatology and vascular medicine) or
specialised private-practice physicians. Patients were considered at high-risk of
infection when presenting with at least three of five selected inflammatory
clinical signs, suggesting a heavy bacterial load (pain between two dressing
changes, erythema, oedema, malodorous wound and presence of a heavy exudate).
They were treated for a maximum period of four weeks, and followed by the
physician on a weekly basis, including a clinical examination, area tracings and
photographs. The primary efficacy criterion of the trial was the relative wound
surface area reduction at the end of the four weeks of treatment. Acceptability
was documented by the nursing staff at each dressing change between the weekly
evaluations. RESULTS: We recruited 37 patients with chronic wounds. Wound surface
area, mostly covered by sloughy tissue, was reduced by 32.5% at the end of the
treatment (median value), while the clinical score (maximum value of 5, based on
inflammatory clinical signs) decreased from 4.0 to 2.0. Effective debridement
properties were documented (62.5% relative reduction of sloughy tissue at week 4;
58.8% of debrided wounds at week 4) and improvement of the periwound skin status
was noted (healthy for 28.6% of the patients at week 4 versus 2.7% at baseline).
In addition, the tested wound dressing presented a good safety profile associated
to a high level of acceptability, noted by both patients and nursing staff.
CONCLUSION: These clinical data support that the tested dressing is a credible
therapeutic alternative for the management of chronic wounds at risk of infection
with inflammatory signs suggesting heavy bacterial load.
PMID- 27608515
TI - Manuka honey in wound management: greater than the sum of its parts?
AB - Few involved in wound care will have escaped the considerable interest which has
been generated by the resurgence in honey. Equally, there will be many clinicians
around the globe who are wondering why all the fuss, as they will have been using
honey all along. However, even with the advent of 'medical-grade' honey, combined
with considerable research into the numerous potential modes of action, there
remains a lingering scepticism regarding the value of honey as a justified,
modern intervention in wound care. The purpose of this brief review is to
summarise the ongoing chemical, biochemical and microbiological research and to
correlate it with clinical outcomes. The purpose being to present the enquiring
clinician with an evidence summary with which clinical choices may be made. While
much of the early research was into generic honeys, one particular source,
manuka, appears especially effective, and as such this has been the focus of
recent studies.
PMID- 27608516
TI - Honey for wound care in the 21st century.
AB - This review is written in memory of Professor Peter Molan, who published a paper
in the Journal of Wound Care in 1999 describing the therapeutic properties of
honey in relation to wound care. It provides an update to show how our
understanding of the mode of action of honey has changed within the past 17
years.
PMID- 27608517
TI - Letters.
PMID- 27608518
TI - Enhancing skin integrity: an interprofessional approach.
AB - Earlier this year the University of Huddersfield's Institute of Skin Integrity
and Infection Prevention in association with the Journal of Wound Care (JWC) held
the first International Skin Integrity and Infection Prevention Conference. The 2
day event consisted of a mix of keynotes, symposia and short presentations from
key opinion leaders and post graduate research students. Here Professor Karen
Ousey and Dr Rachel Webb present the highlights of this event.
PMID- 27608519
TI - Stable 3,6-Linked Fluorenyl Radical Oligomers with Intramolecular
Antiferromagnetic Coupling and Polyradical Characters.
AB - Organic radicals display unique physical structures and could become next
generation functional materials. However, design and synthesis of stable neutral
radicals with a significant polyradical character has been an enormous challenge
for chemists. In this work, we synthesized a series of stable 3,6-linked,
kinetically blocked fluorenyl radical oligomers up to hexamer (FR-n, n = 1-6).
Their ground-state geometric and electronic structures were systematically
studied by various experimental methods including X-ray crystallographic
analysis, variable temperature nuclear magnetic resonance, electron spin
resonance, and superconducting quantum interference device measurements,
supported by density functional theory and ab initio calculations. Moderate
antiferromagnetic coupling between the fluorenyl radicals was observed, and
moderate to large diradical and polyradical characters were calculated from dimer
onward. Furthermore, their photophysical properties were estimated by steady
state, transient absorption, and two-photon absorption measurements, and their
electrochemical properties were investigated by cyclic voltammetry/differential
pulse voltammetry and spectro-electrochemical measurements. A clear chain length
dependence of their optical, electrochemical, and magnetic properties was found
for the oligomers with an odd or even number of spin centers, respectively.
PMID- 27608520
TI - Paediatric hearing aid management: a demonstration project for using virtual
visits to enhance parent support.
AB - OBJECTIVE: The purpose of this study was to explore the use of virtual visits to
monitor hearing aid use with data logging measurements and provide parent support
for hearing aid management. DESIGN: A 6-month longitudinal case study design was
used. STUDY SAMPLE: Four families and two providers participated. RESULTS:
Average hours of daily hearing aid use increased 3.5 h from the beginning to the
end of the study period. Prior to receiving virtual visits, the parents and the
clinicians generally indicated they were hopeful about the benefits of virtual
visits including the frequency and convenience of the appointments but had some
concerns about technical difficulties. These concerns diminished at the
conclusion of the study. CONCLUSION: Virtual visits provided benefits to families
including flexibility and timely access to support. The ability to collect data
logging information more frequently was important for effective problem-solving
to increase hearing aid use. Both parents and clinicians were accepting of tele
support. Parents and professionals would benefit from technology that allows them
to access data logging information more easily and frequently.
PMID- 27608522
TI - Holding on to false beliefs: The bias against disconfirmatory evidence over the
course of psychosis.
AB - BACKGROUND AND OBJECTIVES: The ability to integrate evidence into a reasoning
process is crucial in order to react to changing information, e.g. to adapt one's
beliefs according to new evidence or to generate new beliefs when facing better
alternatives. Evidence integration ability is thus associated with belief
flexibility. A specific bias of evidence integration, a bias against
disconfirmatory evidence (BADE), can be found in patients with schizophrenia and
has been linked to delusion development and maintenance. Knowledge about whether
the BADE occurs already in risk constellations of psychosis can clarify its role
in the pathogenesis of psychosis. METHODS: This article reviews the current
literature on BADE. Many studies demonstrate BADE over the course of illness,
ranging from healthy controls with subclinical properties of schizotypy, over
patients with at-risk mental states (ARMS) and patients with a first episode of
psychosis to patients with chronic schizophrenia. These data allow a comparison
of competences and deficits over the course of illness. Underlying mechanisms of
BADE are discussed, including interrelations with neurocognitive performance and
dopaminergic processes. RESULTS: The BADE could be found in different phases of
psychosis development and can be regarded as a cognitive marker of the beginning
psychotic state. LIMITATIONS: The presented findings are derived from independent
cross-sectional studies. So far, no comprehensive longitudinal assessment has
been published. CONCLUSIONS: Treatments of metacognitive deficits in general and
as early as in the ARMS might interfere with the cognitive pathogenesis of
psychosis, and thereby ameliorate, postpone or even prevent the transition to
psychosis.
PMID- 27608521
TI - Survival and reproduction of Onthophagus landolti (Coleoptera: Scarabaeidae)
exposed to ivermectin residues in cattle dung.
AB - Two bioassays were conducted in parallel to assess the effects of cattle treated
with either 1% ivermectin (IVM) or 3.15% IVM (dosed at 0.2 and 0.63 mg kg-1,
respectively) on reproduction and survival of Onthophagus landolti Harold. Adult
beetles were exposed 10 days to faeces of treated cattle starting at: one day
before treatment (controls), 3, 6, 14, 28 and 35 days post-treatment. Adult
survival of O. landolti was not affected by either of the two treatments. Faecal
residues of 1% IVM almost completely suppressed fecundity of beetles at 3, 6 and
14 days post-treatment (dPT), and reduced fecundity of O. landolti at 28 dPT (
38.3%), relative to controls. Meanwhile, IVM residues after treatment with 3.15%
IVM almost completely suppressed fecundity of beetles at 3, 6, 14 and 28 dPT, and
reduced fecundity of O. landolti at 35 dPT (80.9%), relative to controls. Larval
survival was significantly reduced only at 3 dPT with 1% IVM. Meanwhile,
treatment with 3.15% IVM significantly reduced larval survival at 6, 14 and 28
dPT. Larval mortality was recorded only in L-I and L-II instars. Moreover, in
both bioassays, most of the L-I and L-II specimens that survived showed signs of
toxicity. In conclusion, residual IVM in cattle faeces after treatment with
injectable IVM has a detrimental effect on the fecundity of adult O. landolti up
to 4 weeks post-treatment and on the subsequent larval survival.
PMID- 27608523
TI - Impact of including growth, carcass and feed efficiency traits in the breeding
goal for combined milk and beef production systems.
AB - Improving feed efficiency in dairy cattle could result in more profitable and
environmentally sustainable dairy production through lowering feed costs and
emissions from dairy farming. In addition, beef production based on dairy herds
generates fewer greenhouse gas emissions per unit of meat output than beef
production from suckler cow systems. Different scenarios were used to assess the
profitability of adding traits, excluded from the current selection index for
Finnish Ayrshire, to the breeding goal for combined dairy and beef production
systems. The additional breeding goal traits were growth traits (average daily
gain of animals in the fattening and rearing periods), carcass traits (fat
covering, fleshiness and dressing percentage), mature live weight (LW) of cows
and residual feed intake (RFI) traits. A breeding scheme was modeled for Finnish
Ayrshire under the current market situation in Finland using the deterministic
simulation software ZPLAN+. With the economic values derived for the current
production system, the inclusion of growth and carcass traits, while preventing
LW increase generated the highest improvement in the discounted profit of the
breeding program (3.7%), followed by the scenario where all additional traits
were included simultaneously (5.1%). The use of a selection index that included
growth and carcass traits excluding LW, increased the profit (0.8%), but reduced
the benefits resulted from breeding for beef traits together with LW. A moderate
decrease in the profit of the breeding program was obtained when adding only LW
to the breeding goal (-3.1%), whereas, adding only RFI traits to the breeding
goal resulted in a minor increase in the profit (1.4%). Including beef traits
with LW in the breeding goal showed to be the most potential option to improve
the profitability of the combined dairy and beef production systems and would
also enable a higher rate of self-sufficiency in beef. When considering feed
efficiency related traits, the inclusion of LW traits in the breeding goal that
includes growth and carcass traits could be more profitable than the inclusion of
RFI, because the marginal costs of measuring LW can be expected to be lower than
for RFI and it is readily available for selection. In addition, before RFI can be
implemented as a breeding objective, the genetic correlations between RFI and
other breeding goal traits estimated for the studied population as well as
information on the most suitable indicator traits for RFI are needed to assess
more carefully the consequences of selecting for RFI.
PMID- 27608524
TI - Implementation of an Emergency Department Sepsis Bundle and System Redesign: A
Process Improvement Initiative.
AB - BACKGROUND: In 2008-2009, the Canadian Institute for Health Information reported
over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost
4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to
remain greater than 30% in Canada and are significantly higher than other
critical conditions treated in the emergency department (ED). Our group formed a
multidisciplinary sepsis committee, conducted an ED process of care analysis, and
developed a quality improvement protocol. The objective of this study was to
evaluate the effects of this sepsis management bundle on patient mortality.
METHODS: This before and after study was conducted in two large Canadian tertiary
care EDs and included adult patients with suspected severe infection that met at
least two systemic inflammatory response syndrome (SIRS) criteria. We studied the
implementation of a sepsis bundle including triage flagging, RN medical
directive, education campaign, and a modified sepsis protocol. The primary
outcomes were 30-day all-cause mortality and sepsis protocol use. RESULTS: We
included a total of 167 and 185 patients in the pre- and post-intervention
analysis, respectively. Compared to the pre-intervention group, mortality was
significantly lower in the post-intervention group (30.7% versus 17.3%; absolute
difference, 13.4%; 95% CI 9.8-17.0; p=0.006). There was also a higher rate of
sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute
difference 60.2%; 95% CI 55.1-65.3; p<0.001). Additionally, we found shorter time
intervals from triage to MD assessment, fluid resuscitation, and antibiotic
administration as well as lower rates of vasopressor requirements and ICU
admission. Interpretation The implementation of our multidisciplinary ED sepsis
bundle, including improved early identification and protocolized medical care,
was associated with improved time to achieve key therapeutic interventions and a
reduction in 30-day mortality. Similar low-cost initiatives could be implemented
in other EDs to potentially improve outcomes for this high-risk group of
patients.
PMID- 27608525
TI - Validation of the French version of the Burn Specific Health Scale-Brief (BSHS-B)
questionnaire.
AB - INTRODUCTION: The Burn Specific Health Scale-Brief questionnaire is a widely
validated tool for estimating the health related quality of life and for
assessing the best multidisciplinary management of burn patients. The aim of this
study was to translate the BSHS-B into French and to investigate its reliability
and validity. METHODS: According to the procedure proposed by the Scientific
Advisory Committee of the Medical Outcomes Trust, the Burn Specific Health Scale
Brief (BSHS-B) was translated from the English version into French. In order to
test the reliability of the French version of the BSHS-B, 53 burn patients French
speakers completed the BSHS-B and SF-36 questionnaires from two to four years
after burn. Ten of them have been re-tested at 6 months after the first
evaluation. To evaluate clinical utility of the BSHS-F, internal consistency,
construct validity (using SF-36) and stability in time were assessed using
Cronbach's alpha statistic, Spearman rank test, and intra-class correlation
coefficient respectively. RESULTS: The French version of the BSHS-B Cronbach's
alpha coefficient was 0.93 and was >0.80 for all the sub-domains. French version
of the BSHS-B and the SF-36 were positively correlated, all the associations were
statistically significant (p<0.01). Intra-class correlation coefficients for test
retest ranged between 0.95 and 0.99 for the sub-domains. The intra-class
correlation coefficient (ICC) for the total score was 0.98. CONCLUSION: The
French version of the BSHS-B shows a robust rate of internal consistency,
construct validity and stability in time, supporting its application in routine
clinical practice as well as in international studies.
PMID- 27608526
TI - Optical coherence tomography analysis of hydrofluoric acid decontamination of
human cornea by mannitol solution.
AB - PURPOSE: To evaluate the efficacy of mannitol solution as a decontamination agent
on the chemical burn of the human corneas. METHODS: Eight donor corneas from an
eye bank were exposed to 25MUl of 2.5% hydrofluoric acid (HF) solution on a
filter paper for 20s. Three eyes were rinsed with 1000ml of mannitol 20% for
15min immediately after removal of the filter paper, 3 other were rinsed with
sodium chloride (NaCl) 0.9% (1000ml for 15min) and two eyes were not rinsed.
Microstructural changes were monitored in the time domain by optical coherence
tomography (OCT) imaging for 75min. RESULTS: NaCl reduced the penetration depth
to approximately half the thickness of the cornea at 15min; scattering within the
anterior cornea was higher than that for the unrinsed eye. With mannitol, no
increased scattering was observed in the posterior part of the corneal stroma
within a time period of 1h after rinsing. OCT images revealed low-scattering
intensity within the anterior stroma at the end of the rinsing period.
CONCLUSION: In eye bank human corneas, mannitol proved to be an efficient agent
to decontaminate HF burn.
PMID- 27608527
TI - Chinese academic contribution to burns: A comprehensive bibliometrics analysis
from 1985 to 2014.
AB - OBJECTIVE: The objective of this study was to conduct a survey of the academic
contribution and influence of Chinese scholars in the field of burns. METHOD: The
PubMed database was searched to obtain literature items originating from various
countries and Chinese provinces from 1985 to 2014. The citation data were
collected through the Google Scholar engine. RESULTS: A total of 1037 papers
published in 256 journals were included in this survey. China was second only to
the USA in the number of publications on burns since 2010. In addition, the
annual number of papers has increased significantly since 2001. The journal Burns
published the most number of articles, but its proportion has been decreasing. Of
the papers included in the survey, 58.34% were published in journals with a 5
year impact factor between 1 and 2, whereas only 3.66% were published in journals
with an impact factor >5. Both total citations and citations per paper have
decreased in the past decade. Randomized controlled trials or systematic reviews
merely accounted for a small proportion. Twenty-nine provinces including 64
cities contributed one paper at least. The publications from Taiwan, Beijing,
Chongqing, Shanghai, and Guangdong were high in both quantity and quality.
CONCLUSION: The Chinese academic contribution to the field of burns is now on a
rise. Although the quality of papers is lagging behind quantity, scholars and
academies are dedicated to improving China's academic level.
PMID- 27608528
TI - Factors predicting health status and recovery of hand function after hand burns
in the second year after hospital discharge.
AB - INTRODUCTION: Hands are the most commonly burnt body part given humans' innate
response to guard their face from injury, and are known to have detrimental
functional and psychological consequences. Conflicting evidence exists regarding
the impact of hand burns on long-term health status and global functioning. The
objective of this study was to identify patient and clinical characteristics that
predict health status and hand function of people at 12-24 months after hand
burn. METHODS: The Burns Specific Health Scale-Brief (BSHS-B) and the Brief
Michigan Hand Outcome Questionnaire (Brief MHQ) were administered to community
dwelling adults who were between one and two years after admission to a statewide
burns service for burns including one or both hands. Demographic, injury, and
treatment data were collected to identify which factors predict health status and
hand function in the second year after admission. Linear regression analyses
adjusted for total burn surface area and burn depth were conducted to identify
important predictors or outcomes. RESULTS: The sample (n=41) was 80.5% male, with
a mean age of 44.5 years and total body surface area (TBSA) of 8.4%. Psychiatric
illness (regression coefficient -56.6, confidence interval (95% CI) -76.70,
36.49) and female gender (-20.3; 95% CI -0.77, -40.29) were key predictors of
poorer global health status on the BSHS-B. Females also scored worse on body
image (-5.35; 95% CI -1.83, -8.87) and work (-4.13; 95% CI -0.64, -7.62) domains
of BSHS-B. The need for reconstructive or secondary surgery (-38.84; 95% CI
58.04, -19.65) and female gender (-16.30; 95% CI -4.03, -28.57) were important
predictors of poorer hand function. CONCLUSION: Women and those with a history of
psychiatric illness are particularly vulnerable to poorer outcomes in health
status and/or hand function after burns, and may benefit from more intensive
rehabilitation support and long-term follow-up.
PMID- 27608529
TI - COST OF INTENSIVE CARE IN INDIA.
AB - OBJECTIVES: The majority of patients in India access private sector providers for
curative medical services. However, there is scanty information on the cost of
treatment of critically ill patients in this setting. The study evaluates the
cost and extent of financial subsidy required for patients admitted to an
intensive care unit (ICU) in India. METHODS: Data on direct medical, direct
nonmedical, and indirect cost were prospectively collected from critically ill
patients admitted to a tertiary teaching hospital in India. Willingness-to-pay
(WTP) amount was obtained from the next-of-kin following admission and the actual
cost paid by the family at discharge was recorded. RESULTS: The main diagnoses (n
= 499) were infection (26 percent) and poisoning (21 percent). The mean APACHE-II
score was 13.9 (95 percent confidence interval [CI], 13.3-14.5); 86 percent were
ventilated. ICU stay was 7.8 days (95 percent CI, 7.3-8.3). Hospital mortality
was 27.9 percent. Direct medical cost accounted for 77 percent (US$ 2164) of the
total treatment cost (US$ 2818). Indirect cost and direct nonmedical cost
contributed to 19 percent (US$ 547.5) and 4 percent (US$ 106.5), respectively.
Average total and daily ICU cost were US$ 1,897 and US$ 255, respectively.
Although the family's WTP was 53 percent (US$ 1146; 95 percent CI, 1090-1204) of
direct medical cost, their final contribution was 67.7 percent (US$ 1465; 95
percent CI, 1327-1604). CONCLUSIONS: The cost of an ICU admission in our setting
is US$ 2818. Although the family's contribution to expenses exceeded their
initial WTP, a substantial subsidy (33 percent) is still required. Alternate
financing strategies for the poor and optimization of ICU resources are urgently
required.
PMID- 27608530
TI - The hidden simplicity of biology.
AB - Life is so remarkable, and so unlike any other physical system, that it is
tempting to attribute special factors to it. Physics is founded on the assumption
that universal laws and principles underlie all natural phenomena, but is it far
from clear that there are 'laws of life' with serious descriptive or predictive
power analogous to the laws of physics. Nor is there (yet) a 'theoretical
biology' in the same sense as theoretical physics. Part of the obstacle in
developing a universal theory of biological organization concerns the daunting
complexity of living organisms. However, many attempts have been made to glimpse
simplicity lurking within this complexity, and to capture this simplicity
mathematically. In this paper we review a promising new line of inquiry to bring
coherence and order to the realm of biology by focusing on 'information' as a
unifying concept.
PMID- 27608531
TI - Arrested development of abomasal trichostrongylid nematodes in lambs in a steppe
environment (North-Eastern Algeria).
AB - Arrested development of abomasal trichostrongylid nematodes was studied in 30
permanent grazing lambs on a large farm in the North-East of Algeria. The steppe
climate has cold winters and hot and dry summers. The lambs were monitored
monthly for gastrointestinal nematodes using nematode faecal egg counts, from
February 2008 to February 2009. Every 2 months, two of the original 30 permanent
lambs were necropsied after being held in pens for three weeks so that recently
ingested infective larvae could develop into adults. The highest percentage of
fourth stage larvae (L4), reaching 48% of the total worm burden, was recorded in
abomasal contents in June. Teladorsagia and other Ostertagiinae constituted the
highest percentage of L4 larvae (71%), whereas the percentage of Trichostrongylus
(17.4%) or Haemonchus (11.6%) remained low. The dynamics of infection observed
here (highest faecal egg count in August) and the stage composition of worm
burden (highest percentage of L4 in June) provide strong evidence that arrested
development had occurred.
PMID- 27608532
TI - The contribution of at-home and away-from-home food to dietary intake among 2-13
year-old Mexican children.
AB - OBJECTIVE: Away-from-home foods have been shown to have lower nutritional quality
and larger portion sizes than many foods prepared at home. We aimed to describe
energy and nutrient intakes among 2-13-year-old Mexican children by eating
location (at home and away from home), overall, by socio-economic status (SES)
and by urbanicity. DESIGN: Dietary intake was collected via one 24 h recall in
the 2012 Mexican National Health and Nutrition Survey (ENSANUT). Location was
reported for each food consumed. Results were adjusted for sex, day of recall,
region, weight status, SES and urbanicity. SETTING: Mexico (nationally
representative). SUBJECTS: Children aged 2-5 years (n 1905) and 6-13 years (n
2868). RESULTS: Children consumed the majority of daily energy at home (89% of 2
5-year-olds; 82 % of 6-13-year-olds). The most common away-from-home eating
location was school (22 % of 2-5-year-olds; 43 % of 6-13-year-olds), followed by
the street (14 % of 2-5-year-olds; 13 % of 6-13-year-olds). The most common foods
consumed away from home were wheat/rice and corn mixed dishes, sugar-sweetened
beverages, pastries/candy/desserts, milk (2-5-year-olds only) and salty snacks (6
13-year-olds). Multivariate models showed that high-SES 2-5-year-olds consumed 14
% of daily energy away from home v. 8 % among low-SES 2-5-year-olds, and high-SES
6-13-year-olds consumed 21 % of daily energy away from home v. 14 % among low-SES
6-13 year-olds. There were no differences by urban residence. CONCLUSIONS: Among
Mexican children, most foods and beverages were consumed at home. However, the
percentage of foods consumed or purchased away from home increased with age and
with SES.
PMID- 27608533
TI - Direct observation of dynamic modes excited in a magnetic insulator by pure spin
current.
AB - Excitation of magnetization dynamics by pure spin currents has been recently
recognized as an enabling mechanism for spintronics and magnonics, which allows
implementation of spin-torque devices based on low-damping insulating magnetic
materials. Here we report the first spatially-resolved study of the dynamic modes
excited by pure spin current in nanometer-thick microscopic insulating Yttrium
Iron Garnet disks. We show that these modes exhibit nonlinear self-broadening
preventing the formation of the self-localized magnetic bullet, which plays a
crucial role in the stabilization of the single-mode magnetization oscillations
in all-metallic systems. This peculiarity associated with the efficient nonlinear
mode coupling in low-damping materials can be among the main factors governing
the interaction of pure spin currents with the dynamic magnetization in high
quality magnetic insulators.
PMID- 27608535
TI - Re: Coronectomy of lower third molars with and without guided bony regeneration.
PMID- 27608534
TI - Accuracy of both virtual and printed 3-dimensional models for volumetric
measurement of alveolar clefts before grafting with alveolar bone compared with a
validated algorithm: a preliminary investigation.
AB - Our objective was to assess the accuracy of virtual and printed 3-dimensional
models derived from cone-beam computed tomographic (CT) scans to measure the
volume of alveolar clefts before bone grafting. Fifteen subjects with unilateral
cleft lip and palate had i-CAT cone-beam CT scans recorded at 0.2mm voxel and
sectioned transversely into slices 0.2mm thick using i-CAT Vision. Volumes of
alveolar clefts were calculated using first a validated algorithm; secondly,
commercially-available virtual 3-dimensional model software; and finally 3
dimensional printed models, which were scanned with microCT and analysed using 3
dimensional software. For inter-observer reliability, a two-way mixed model
intraclass correlation coefficient (ICC) was used to evaluate the reproducibility
of identification of the cranial and caudal limits of the clefts among three
observers. We used a Friedman test to assess the significance of differences
among the methods, and probabilities of less than 0.05 were accepted as
significant. Inter-observer reliability was almost perfect (ICC=0.987). There
were no significant differences among the three methods. Virtual and printed 3
dimensional models were as precise as the validated computer algorithm in the
calculation of volumes of the alveolar cleft before bone grafting, but virtual 3
dimensional models were the most accurate with the smallest 95% CI and, subject
to further investigation, could be a useful adjunct in clinical practice.
PMID- 27608536
TI - Faith-based intervention to increase fruit and vegetable intake among Koreans in
the USA: a feasibility pilot.
AB - OBJECTIVE: In the USA, adults of Korean descent tend to eat fewer vegetables than
adults in South Korea. The present pilot study examined the feasibility of
developing and implementing a faith-based intervention to improve knowledge,
attitudes and intake of fruit and vegetables (F&V) for Koreans in the USA.
DESIGN: Feasibility pilot using a cluster-randomized intervention trial design.
The multicomponent intervention included motivational interviewing sessions by
telephone and church-based group activities. SETTING: Eleven of the largest
Korean churches in Southern California. SUBJECTS: Adults (n 71) from the eleven
Korean churches. RESULTS: Feasibility was demonstrated for the study procedures,
including recruitment of churches and individual participants. Allocating time
throughout the study for church collaboration and having a study church
coordinator to coordinate multiple churches were crucial. Participants'
attendance at church activities (89 %) and participation by pastors and fellow
churchgoers exceeded expectations. Participants' use of intervention materials
was high (94 % or above) and satisfaction with coaching sessions was also high
(75 % or above). Having a centralized coach trained in motivational interviewing,
instead of one at each church, proved practical. Pilot results are promising for
F&V knowledge, attitudes and behaviours. The intervention group improved
knowledge and intake of the recommended amounts of F&V, above that of the control
group. CONCLUSIONS: This pilot suggests that Koreans in the USA can be reached
through their church and that a faith-based intervention study can be implemented
to increase F&V intake. Preliminary results for the intervention appear promising
but further research is needed to properly evaluate its efficacy.
PMID- 27608537
TI - Telavancin activity tested against a collection of Staphylococcus aureus isolates
causing pneumonia in hospitalized patients in the United States (2013-2014).
AB - Telavancin is approved in the United States and Europe for the treatment of
hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial
pneumonia caused by Staphylococcus aureus. This study provides a current in vitro
activity analysis for telavancin and comparators against 1353 United States S.
aureus causing pneumonia in hospitalized patients during 2013-2014. Telavancin
was found to exhibit potent activity (MIC90, 0.06MUg/mL; 16-fold more active than
vancomycin or linezolid) against all S. aureus isolates, including the HABP
subset, multidrug-resistant isolates, and those less susceptible to vancomycin.
PMID- 27608538
TI - In vitro antifungal susceptibility profiles of Cryptococcus species isolated from
HIV-associated cryptococcal meningitis patients in Zimbabwe.
AB - Cryptococcus neoformans is the leading cause of cryptococcosis in HIV-infected
subjects worldwide. Treatment of cryptococcosis is based on amphotericin B,
flucytosine, and fluconazole. In Zimbabwe, little is known about antifungal
susceptibility of Cryptococcus. Sixty-eight genotyped Cryptococcus isolates were
tested for antifungal profiles. Amphotericin B, isavuconazole, and voriconazole
showed higher activity than other triazoles. Fluconazole and flucytosine were
less effective, with geometric mean MICs of 2.24 and 2.67mg/L for C. neoformans
AFLP1/VNI, 1.38 and 1.53mg/L for C. neoformans AFLP1A/VNB/VNII and AFLP1B/VNII,
and 1.85 and 0.68mg/L for Cryptococcus tetragattii, respectively. A significant
difference between flucytosine geometric mean MICs of C. neoformans and C.
tetragattii was observed (P=0.0002). The majority of isolates (n=66/68; 97.1%)
had a wild-type MIC phenotype of all antifungal agents. This study demonstrates a
favorable situation with respect to the tested antifungals agents. Continued
surveillance of antifungal susceptibility profiles is important due to the high
burden of cryptococcosis in Africa.
PMID- 27608539
TI - Evaluation of a commercial immunochromatographic assay for rapid routine
identification of PBP2a-positive Staphylococcus aureus and coagulase-negative
staphylococci.
AB - We evaluated the performance of an immunochromatographic assay (PBP2a Culture
Colony Test - AlereTM), detecting protein-binding penicillin 2a on staphylococci
primary isolates in only 6minutes. The assay is highly sensitive for the direct
detection of MRSA on various culture media whereas it requires cefoxitin
induction for methicillin-resistant coagulase-negative staphylococci.
PMID- 27608540
TI - Trends in work disability with mental diagnoses among social workers in Finland
and Sweden in 2005-2012.
AB - : Aims Social workers report high levels of stress and have an increased risk for
hospitalisation with mental diagnoses. However, it is not known whether the risk
of work disability with mental diagnoses is higher among social workers compared
with other human service professionals. We analysed trends in work disability
(sickness absence and disability pension) with mental diagnoses and return to
work (RTW) in 2005-2012 among social workers in Finland and Sweden, comparing
with such trends in preschool teachers, special education teachers and
psychologists. METHODS: Records of work disability (>14 days) with mental
diagnoses (ICD-10 codes F00-F99) from nationwide health registers were linked to
two prospective cohort projects: the Finnish Public Sector study, years 2005-2011
and the Insurance Medicine All Sweden database, years 2005-2012. The Finnish
sample comprised 4849 employees and the Swedish 119 219 employees covering four
occupations: social workers (Finland 1155/Sweden 23 704), preschool teachers
(2419/74 785), special education teachers (832/14 004) and psychologists
(443/6726). The reference occupations were comparable regarding educational
level. Risk of work disability was analysed with negative binomial regression and
RTW with Cox proportional hazards. RESULTS: Social workers in Finland and Sweden
had a higher risk of work disability with mental diagnoses compared with
preschool teachers and special education teachers (rate ratios (RR) 1.43-1.91),
after adjustment for age and sex. In Sweden, but not in Finland, social workers
also had higher work disability risk than psychologists (RR 1.52; 95% confidence
interval 1.28-1.81). In Sweden, in the final model special education teachers had
a 9% higher probability RTW than social workers. In Sweden, in the final model
the risks for work disability with depression diagnoses and stress-related
disorder diagnoses were similar to the risk with all mental diagnoses (RR 1.40
1.77), and the probability of RTW was 6% higher in preschool teachers after work
disability with depression diagnoses and 9% higher in special education teachers
after work disability with stress-related disorder diagnoses compared with social
workers. CONCLUSION: Social workers appear to be at a greater risk of work
disability with mental diagnoses compared with other human service professionals
in Finland and Sweden. It remains to be studied whether the higher risk is due to
selection of vulnerable employees to social work or the effect of work-related
stress in social work. Further studies should focus on these mechanisms and the
risk of work disability with mental diagnoses among human service professionals.
PMID- 27608541
TI - Relationship between interleukin-1beta and depressive disorder after acute
coronary syndrome.
AB - This study was aimed to investigate the effect of serum interleukin (IL)-1beta in
the depression trajectory after acute coronary syndrome (ACS) considering two IL
1beta polymorphisms: -511C/T or +3953C/T. A total of 969 patients were evaluated
within 2weeks after ACS and of these, 711 were followed-up 1year later.
Depressive disorders were evaluated at baseline and 1year after ACS, using the
Mini-International Neuropsychiatric Interview. Serum IL-1beta levels and IL-1beta
genotypes were investigated at baseline. Covariates on socio-demographic and
clinical characteristics including depressive symptoms, cardiovascular risk
factors, and current cardiac status were assessed. Depression during the acute
ACS was significantly associated with the IL-1beta levels and the -511T allele.
The interaction of the IL-1beta level with depression at baseline in the presence
of the -511T allele was also significant. No associations were found with
depression during the chronic ACS. For the +3953C/T genotype, there was no
association with depression in either the acute or chronic phase. The IL-1beta
level and -511C/T genotype, separately or interactively, could be a biomarker for
depressive disorder in the acute phase of ACS. Focused interventions for those
with higher IL-1beta level and -511T allele might reduce the risk of depressive
disorder.
PMID- 27608542
TI - Exact inference for the risk ratio with an imperfect diagnostic test.
AB - The risk ratio quantifies the risk of disease in a study population relative to a
reference population. Standard methods of estimation and testing assume a perfect
diagnostic test having sensitivity and specificity of 100%. However, this
assumption typically does not hold, and this may invalidate naive estimation and
testing for the risk ratio. We propose procedures that control for sensitivity
and specificity of the diagnostic test, given the risks are measured by
proportions, as it is in cross-sectional studies or studies with fixed follow-up
times. These procedures provide an exact unconditional test and confidence
interval for the true risk ratio. The methods also cover the case when
sensitivity and specificity differ in the two groups (differential
misclassification). The resulting test and confidence interval may be useful in
epidemiological studies as well as in clinical and vaccine trials. We illustrate
the method with real-life examples which demonstrate that ignoring sensitivity
and specificity of the diagnostic test may lead to considerable bias in the
estimated risk ratio.
PMID- 27608543
TI - Assessment of physical and structural characteristics of almond gum.
AB - Almond gum was investigated for its physical and structural characteristics in
comparison to gum arabic. Among physical properties, bulk density was found to be
0.600+/-0.12g/mL and 0.502+/-0.20g/mL for almond and gum arabic respectively.
Almond gum (0.820+/-0.13g/mL) displayed the maximum value for tapped density.
Compressibility index of exudate gum powders varied from 26.79+/-1.47 to 37.46+/
0.50% and follow the order gum arabic>almond gum. Almond gum demonstrated good
flow characteristics when compared to gum arabic. True density showed significant
difference (p<0.05) among the exudate samples and it was recorded higher for gum
arabic. The maximum value of porosity recorded in case of gum arabic indicates
the presence of large number of interstitial spaces among its particles. Almond
gum had fair flow character while good for the other exudate gum powder. Almond
gum had relatively higher mineral content than gum arabic. The oil holding
capacity of exudate gums varied from 0.87+/-0.05 to 0.92+/-0.02g/g. Exudate
powder samples were found to lie in the first quadrant of the hue angle (0-90
degrees ) corresponding to the range of reddish-purple to yellow. The absence of
peaks in the X-ray diffractograms of exudate samples reflects their amorphous
nature. SEM micrographs revealed a lot of variability in shape and size of the
exudate particles.
PMID- 27608544
TI - An alternative allosteric pathway in thermophilic methylglyoxal synthase.
AB - Methylglyoxal synthase (MGS) is a homohexameric enzyme responsible for converting
dihydroxyacetone phosphate (DHAP) to methylglyoxal and phosphate in the
methylglyoxal bypass of glycolysis. Phosphate acts as an allosteric inhibitor and
strong regulator for this enzyme. Previous studies on MGS from Thermus sp. GH5
(TMGS) had indicated a pathway for transmitting the signal through Pro82, Arg97
and Val101 to the active site. The necessity of these residues for heterotropic
negative cooperativity between subunits of TMGS were also proposed. In this
study, it has been shown that a path via a salt bridge between Arg80 and Asp100
in the narrow dimer interface provides an alternative pathway for transmission of
the allosteric inhibitory signal through subunit interfaces.
PMID- 27608545
TI - Evaluation of mixing efficiency in elaborating of chitosan/cellulose
nanocomposite via statistical analyses.
AB - Casting films of chitosan (CS)/cellulose nanofibers (CNF) biocomposites
containing 0.5-5wt.% of CNF were prepared. Mechanical and physical properties
along with scanning electron microscope (SEM) study revealed the best properties
for the nanocomposite containing 3wt.% of CNF. Exceeding than this CNF content
led to aggregation phenomenon. Then this optimized content nanocomposite was
selected in order to investigate the effect of mixing condition on the
properties. In the first method the CS and CNF were added simultaneously under
ultrasound irradiation. In another method dispersion of CNF was carried out in
the solvent separately and then added to the CS solution using ultrasound system.
SEM images of the nanocomposites indicated occurrence of aggregation in the
simultaneous addition of CS and CNF method. A statistical analysis showed that
the best method for effective distribution and dispersion of the nanoparticles
within the CS was dispersion of CNF separately in the solvent and addition to the
CS solution along with ultrasonic wave's irradiation. The ultrasound induced
mixing had a significant effect on the dispersion of the nanoparticles, resulting
in significant differences in almost the properties of the nanocomposites.
PMID- 27608546
TI - Chitosan: An efficient biomacromolecule support for synergic catalyzing of
Hantzsch esters by CuSO4.
AB - The synergic effect of the chitosan biomacromolecule support for catalyzing of
Hantzsch esters formation by CuSO4 has been demonstrated for one-pot and
efficient pseudo-four-component reaction to afford a wide range of 1,4
dihydropyridine (DHP) or polyhydroquinoline (PHQ) derivatives. The desired
products were simply prepared from different aldehydes, beta-dicarbonyls and
ammonium acetate in the presence of a low loading of chitosan supported
copper(II) sulfate (CSCS) in EtOH under reflux conditions. The biodegradable CSCS
catalyst was characterized by field emission scanning electron microscopy (FESEM)
and energy-dispersive X-ray spectroscopy analysis (EDX) methods as well as
coupled plasma-atomic emission (ICP-AE) and FT-IR spectroscopy. The CSCS catalyst
is recyclable and reused four times without significant loss of its activity.
PMID- 27608547
TI - Effect of guar and xanthan gums on functional properties of mango (Mangifera
indica) kernel starch.
AB - The effects of different concentrations of guar and xanthan gums on functional
properties of mango kernel starch (MKS) were studied. Both guar and xanthan gum
enhanced the water absorption of MKS. The addition of xanthan gum appeared to
reduce the SP (swelling power) and solubility at higher temperatures while guar
gum significantly enhanced the SP as well as solubility of MKS. The addition of
both gums produced a reinforcing effect on peak viscosity of MKS as compared to
control. Pasting temperature of MKS was higher than that of starch modified by
gums indicating ease of gelatinization. Guar gum played an accelerative effect on
setback but xanthan gum delayed the setback phenomenon during the cooling of the
starch paste. Both gums were found to be effective in reducing the syneresis
while gel firmness was markedly improved.
PMID- 27608550
TI - Empirical Bayes estimation of farm prevalence adjusting for multistage sampling
and uncertainty in test performance: a Brucella cross-sectional serostudy in
southern Kazakhstan.
AB - Estimation of farm prevalence is common in veterinary research. Typically, not
all animals within the farm are sampled, and imperfect tests are used. Often,
assumptions about herd sizes and sampling proportions are made, which may be
invalid in smallholder settings. We propose an alternative method for estimating
farm prevalence in the context of Brucella seroprevalence estimation in an
endemic region of Kazakhstan. We collected 210 milk samples from Otar district,
with a population of about 1000 cattle and 16 000 small ruminants, and tested
them using an indirect ELISA. Individual-level prevalence and 95% confidence
intervals were estimated using Taylor series linearization. A model was developed
to estimate the smallholding prevalence, taking into account variable sampling
proportions and uncertainty in the test accuracy. We estimate that 73% of
households that we sampled had at least one Brucella-seropositive animal (95%
credible interval 68-82). We estimate that 58% (95% confidence interval 40-76) of
lactating small ruminants and 14% (95% confidence interval 1-28) of lactating
cows were seropositive. Our results suggest that brucellosis is highly endemic in
the area and conflict with those of the official brucellosis-testing programme,
which found that in 2013 0% of cows and 1.7% of small ruminants were
seropositive.
PMID- 27608548
TI - The Implementation of Internet Interventions for Depression: A Scoping Review.
AB - BACKGROUND: Depression is one of the most common mental health problems among
adults, but effective treatments are not widely accessible. The Internet holds
promise as a cost-effective and convenient delivery platform of interventions for
depression. However, studies suggest that Internet interventions are not widely
available in routine settings. OBJECTIVE: The aim of this study was to review the
literature and examine whether there are systematic differences in reporting of
the various implementation components on Internet interventions for depression,
and then to examine what is known about and is characteristic of the
implementation of these Internet interventions in regular care settings. METHODS:
We performed a scoping review, drawing upon a broad range of the literature on
Internet interventions for depression in regular care, and used the active
implementation framework to extract data. RESULTS: Overall, the results suggested
that knowledge about the implementation of Internet interventions for depression
in regular care is limited. However, guided support from health professionals
emphasizing program adherence and recruitment of end users to the interventions
emerged as 2 main themes. We identified 3 additional themes among practitioners,
including their qualifications, training, and supervision, but these were
scarcely described in the literature. The competency drivers (ie, staff and user
selection, training, and supervision) have received the most attention, while
little attention has been given to organizational (ie, decision support,
administration, and system intervention) and leadership drivers. CONCLUSIONS:
Research has placed little emphasis on reporting on the implementation of
interventions in practice. Leadership and organizational drivers, in particular,
have been largely neglected. The results of this scoping review have implications
for future research and efforts to successfully implement Internet interventions
for depression in regular care.
PMID- 27608549
TI - Adaptive Immunity in Fibrosarcomatous Dermatofibrosarcoma Protuberans and
Response to Imatinib Treatment.
AB - Dermatofibrosarcoma protuberans (DFSP), although rare, is the most frequent skin
sarcoma. Here, we focus on DFSP carrying the fibrosarcomatous transformation (FS
DFSP). FS-DFSP responds to imatinib (IM); however, tumor relapse often occurs. In
a series of 21 pre- and post-treatment FS-DFSP samples, the present study
explored the events that occur at the tumor site during IM therapy. Gene
expression profile and immunohistochemistry analyses documented the occurrence of
IM-induced senescence phenotype in the tumor cells and showed the accumulation of
activated CD3+ T cells and CD163+CD14+ myeloid cells expressing the CD209 marker
in post-therapy lesions. In post-IM specimens, the pathological response and
tumor apoptosis were tightly associated with T-cell infiltration, thus suggesting
the presence of an ongoing anti-tumor response, which was further confirmed by in
vitro functional assays with CD3+ T cells isolated from an IM-responding FS-DFSP
lesion. The integration of targeted therapies with immune therapies is currently
under investigation to achieve longer tumor control. Our data outline the in situ
immunological effects of IM and classify IM-treated FS-DFSP as potentially
sensitive to immunotherapy, thus providing the rationale for further
investigations of combination treatment for this soft-tissue sarcoma.
PMID- 27608551
TI - Future-proofing educational guidance.
PMID- 27608552
TI - OMFS: Seven day services.
PMID- 27608553
TI - Brexit: Implications for tooth whitening.
PMID- 27608554
TI - Oral cancer: Breath of death.
PMID- 27608555
TI - Dental education: Mobilising resources.
PMID- 27608556
TI - Khat and cancer.
PMID- 27608558
TI - Silver anniversary for BSG.
PMID- 27608557
TI - Dental research: Quality of life.
PMID- 27608561
TI - Rising to the challenge.
AB - R. S. Austin, K. Ranshi, E. Jones, R. Watt, P. Briggs discuss training our future
dental leaders and managers to make a positive difference against a background of
ever-increasing complexity in NHS organisations.
PMID- 27608562
TI - Outcry over Childhood Obesity Strategy.
PMID- 27608563
TI - Does dried fruit really damage the teeth?
PMID- 27608564
TI - Honours and awards.
PMID- 27608566
TI - Graham Gilmour.
PMID- 27608565
TI - Ian Brack: 'We are going to get better at what we do'.
PMID- 27608567
TI - Peter Alan Long.
PMID- 27608568
TI - Should prospective dental students be screened for colour vision deficits?
AB - A perennial question in dental education is: what skills and aptitudes should be
assessed in prospective dental students? Intellectual capacity and manual
dexterity understandably rank highly, but are there minimum thresholds for visual
perception that applicants need be able to demonstrate before they enter the
profession? We have recently flagged this issue with regard to the thresholds of
stereoscopic acuity required for a dentist when operating on teeth. In the
present article, we highlight the issue of identifying a minimum acceptable level
of colour vision.
PMID- 27608569
TI - How will the obesity epidemic affect dentistry?
AB - A scoping review of the implications of adult obesity in the delivery and
acceptance of dental care.
PMID- 27608570
TI - Oral health is wealth.
AB - The impact of oral conditions on children in England, Wales and Northern Ireland
2013.
PMID- 27608571
TI - Links between deprivation and oral health.
AB - Socioeconomic disadvantage and oral-health-related hospital admissions: a 10-year
analysis.
PMID- 27608572
TI - How oral cancer hits the headlines.
AB - Oral cancer: Exploring the stories in UK newspapers.
PMID- 27608573
TI - Exercise - 'best buy': Update on the global pandemic of physical inactivity.
AB - At least one hour of moderate exercise a day to counteract a sedentary
occupation.
PMID- 27608574
TI - The missing calories: Counting calories. How under-reporting can explain the
apparent fall in calorie intake.
AB - The increase in weight as a consequence of 'every single adult in England jogging
for around an hour less a day, every day, than they were in the 1970s', lacks all
credibility.
PMID- 27608575
TI - Root caries: Risk indicators associated with root caries in independently living
older adults.
AB - Neither those subjects who wore dentures, nor those who harboured caries
associated microorganisms had a higher prevalence of root caries.
PMID- 27608576
TI - Inequalities in preventive and restorative dental services in England, Wales and
Northern Ireland.
AB - Aims The objective of this study is to assess socioeconomic inequalities in the
use of selected dental procedures.Methods Data is from the Adult Dental Health
Survey 2009, a nationally representative cross-sectional survey of England,
Northern Ireland and Wales. Overall, 6,279 participants were included in the
analysis. Occupational classification and education were used to assess
variations in the use of preventive, restorative services and tooth extraction
using a series of logistic regression models, adjusting for age, sex, ethnicity,
DMFT, self-reported oral health, dental visits and country.Results There were
clear socioeconomic variations in the utilisation of preventive and restorative
services. In the fully adjusted model those with no educational qualification
were less likely to report ever having preventive services than those with a
degree (OR 0.48, 95%CI: 0.36,0.65). Similarly, individuals in routine/manual
occupation were significantly less likely to report ever having preventive
services than those in managerial/professional occupation (OR 0.58, 95%CI:
0.46,0.74) in the fully adjusted model.Conclusion The findings imply that despite
relatively equitable access and higher use of dental services in UK, the least
educated and those at the bottom of social hierarchy are less likely to have
preventive and restorative dental services.
PMID- 27608577
TI - Musculoskeletal neck and back pain in undergraduate dental students at a UK
dental school - a cross-sectional study.
AB - Objective Limited data exist on musculoskeletal problems within dental students:
we aimed to determine the prevalence of these disorders.Design Single centre
cross-sectional study.Setting A UK Dental School 2015.Methods Students completed
a modified Nordic pain questionnaire.Main outcome measures Self-reported
frequency and severity of pain, fitness and coping strategies.Results 63% of 390
respondents were female and 75% aged under 23. Seventy-nine percent experienced
pain with 42% experiencing pain for 30 or more days in the past year. Lower back
pain was most common (54%) and was most frequently the worst area of pain (48%).
Thirty-six percent reported pain lasting at least four hours. The mean 'average
pain intensity' VAS score was 3.81/10 (sd = 1.75) and mean 'worst pain intensity'
was 5.56 (sd = 2.10). More females reported neck pain (58% versus 37%, P <0.001)
and higher 'average pain intensity' (mean 4.02, sd 1.82 versus 3.43 sd 1.55, P =
0.012. Daily stretching was used by 55.7% of respondents, and this positively
correlated with 'average' and 'worst pain intensity' (P = 0.096 and P = 0.001)
scores. Eighteen percent sought professional help to manage pain.Conclusion
Musculoskeletal pain is a problem for dental students. Education in self-care may
be helpful; however, assessments of possible interventions are needed.
PMID- 27608578
TI - Oral cancer: exploring the stories in United Kingdom newspaper articles.
AB - Objective Reports suggest that patients with oral cancer delay seeking help
because they are unaware of the symptoms. The majority of adults (95%) engage
with news reports and 40% read newspapers. Newspaper oral cancer stories may
influence awareness and health-seeking behaviour. The aim of this study was to
explore how oral cancer is portrayed in UK newspaper print media.Design
Qualitative content analysis of articles from ten newspapers with the widest UK
print circulation. All articles using the terms 'mouth cancer' and 'oral cancer'
over a three year period were retrieved. Duplicates, non-cancer and non-human
articles were excluded.Results 239 articles were analysed. Common topics included
'recent research', 'survivor stories', 'health information' and 'celebrity
linkage'. Articles were often emotive, featuring smoking, alcohol, sex and
celebrity. Articles lacked a proper evidence base and often failed to provide
accurate information about signs and symptoms, information about prevention and
signposting to treatment.Conclusions Opportunities to save lives are being
missed. Further work to improve social responsibility in the media and develop
guidance to enhance the quality of information, health reporting and signposting
to help are indicated.
PMID- 27608579
TI - A scoping review of the implications of adult obesity in the delivery and
acceptance of dental care.
AB - Background Due to the increasing prevalence of obesity within the general
population it is presumed that the prevalence of overweight and obese adults
accessing dental services will also increase. For this reason dentists need to be
aware of implications of managing such patients.Methods A scoping review was
carried out. Both Medline via OVID and Scopus databases were searched along with
grey literature databases and the websites of key organizations. Inclusion and
exclusion criteria were established. The data were collected on a purpose-made
data collection form and analysed descriptively.Results The review identified 28
relevant published articles and two relevant items of grey literature. Following
review of this literature three themes relating to adult obesity in the delivery
and acceptance of dental care emerged; clinical, service delivery and patient
implications. The majority of the papers focused on the clinical
implications.Conclusion On the topic of adult obesity and dental care, the
majority of published and grey literature focuses on the clinical implications.
Further research is needed on both the patients' perspectives of being overweight
or obese and the delivery and acceptance of dental care and the service delivery
implications.
PMID- 27608580
TI - The Overseas Registration Examination of the General Dental Council.
AB - The Overseas Registration Examination is a route to entry to the UK Dentists
Register for dentists who have qualified outside the European Economic Area. The
role of the examination is to protect the public by ensuring that such dentists
meet minimum standards of competence. Candidates invest considerable time and
resource in attempting the examination. For these reasons it is essential that
the examination is both robust and fair. This paper describes the fundamental
principles of assessment underpinning the design of the examination and the steps
taken by the General Dental Council's ORE Advisory Group to assure its ongoing
quality.
PMID- 27608581
TI - Oral health behaviours of children in England, Wales and Northern Ireland 2013.
AB - Background The 2013 Children's Dental Health Survey is the fifth in a series of
national surveys.Aim To describe the oral health behaviours in children and
adolescents in England, Wales and Northern Ireland.Method A representative sample
of children (aged 5, 8 12 and 15 years) in England, Wales and Northern Ireland
were invited to participate in dental examinations. Children and parents were
also invited to complete a questionnaire about oral health behaviours.Results
Overall, the majority of children and young people reported good oral health
behaviours. For example, more than three quarters of the 12- and 15-year-olds
reported brushing their teeth twice a day or more often. However, a sizeable
proportion of the sample reported less positive behaviours. Nearly 30% of 5-year
olds first started to brush their teeth after the age of one year. Among 15-year
olds, 11% were current smokers and 37% reported that they currently drank
alcohol. Sixteen percent of 12-year-olds reported to consume drinks containing
sugar four or more times a day. Of particular concern was the marked differences
that existed by level of deprivation. Children living in lower income households
(eligible for free school meals) were less likely to brush their teeth twice a
day, more likely to start brushing after six months, more likely to be a smoker
and more likely to consume frequent amounts of sugary drinks.Conclusion Despite
some encouraging overall patterns of good oral health behaviours, a sizeable
proportion of children and young people reported behaviours that may lead to
poorer oral and general health. Preventive support should be delivered in
clinical dental settings to encourage positive oral health behaviours. Public
health strategies are also needed to reduce inequalities in oral health
behaviours among children and young people.
PMID- 27608590
TI - Biggest Dental Showcase comes to ExCeL, London.
AB - This is your show so come and see what it has to offer you.
PMID- 27608585
TI - Three steps to a healthy mouth.
AB - This article presents the evidence supporting the use of a three-step home care
regimen to maintain good oral health. Brought to you by Johnson &Johnson, the
makers of LISTERINE((r)).
PMID- 27608594
TI - PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes
mellitus. Results from the genetics of atherosclerotic disease Mexican study.
AB - The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene
hydrolyzes phospholipids liberating free fatty acids (FFAs) and
lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo
a continuous release into circulation. A sustained excessive increase in this
release contributes to metabolic disease. The aim of the present study was to
evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for
metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican
population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156)
were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with
T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant
1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body
mass index (BMI), smoking habit, and hypertension, the rs876018T allele was
associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005;
OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other
hand, under several models adjusted by the same variables, the rs3753827A
(OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles
(OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were
associated with increased risk of T2DM when compared with controls. In addition,
the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017,
Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS
when compared with controls. Also, this allele was associated with SA in T2DM
patients (Pdom=0.007). The TAG haplotype was significantly associated with
increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A
polymorphisms are involved in the risk of developing MetS and T2D and are
associated with SA in this group of patients.
PMID- 27608595
TI - Clinical practice guidelines for prophylaxis of venous thomboembolism in cancer
patients.
AB - Symptomatic venous thromboembolism (VTE) occurs 4-7 times more frequently in
cancer patients as compared to non-cancer patients. A significant number of risk
factors, which can be subcategorised as patient-, cancer- or treatment-related,
have been shown to influence the risk of VTE during malignancy and further
incorporated in risk-assessment models. Safe and efficient thromboprophylaxis
regimens allow substantial decreased in VTE rates, since VTE is most often a
largely preventable disease, but thromboprophylaxis remains underused in cancer
compared to non-cancer patients. If thromboprophylaxis is warranted in cancer
patients undergoing surgery or hospitalised for acute medical illness or with a
lower mobility in the absence of contraindications to anticoagulants, its benefit
remains controversial in outpatients and may be limited to locally advanced or
metastatic pancreatic or lung cancer treated with chemotherapy. The International
Initiative on Thrombosis and Cancer-CME free mobile app (ios and android), based
on the International Clinical Practice Guidelines (CPG), facilitates their
implementation and dissemination of knowledge worldwide so as to improve VTE
treatment and prophylaxis in cancer patients.
PMID- 27608596
TI - T-3256336, a novel and orally available small molecule IAP antagonist, induced
tumor cell death via induction of systemic TNF alpha production.
AB - Inhibitors of apoptosis proteins (IAPs) are a family of antiapoptotic regulators
that have attracted attention as potential targets for cancer therapeutics.
Although recent studies have revealed that small-molecule IAP antagonists induce
tumor selective cell death in an autocrine tumor necrosis factor (TNF)alpha
dependent manner, the single-agent efficacy of IAP antagonists is restricted to a
small subset of cancer cells. In this study, we showed that the single-agent
activity of T-3256336 was limited to a few cancer cell lines in vitro, and these
cell lines were defined by relatively high levels of TNFalpha mRNA expression.
However, some other cancer cells, including PANC-1 cells, become drastically
sensitive to T-3256336 when costimulated with exogenous TNFalpha. In PANC-1 mouse
xenograft models, the administration of T-3256336 increased levels of several
cytokines including TNFalpha and lead to tumor regression as a single agent,
which was attenuated by the neutralization of circulating mouse TNFalpha with an
antibody. These results suggest dual roles of IAP antagonists, increase systemic
cytokines including TNFalpha, and sensitization of tumors to IAP antagonist
induced death.
PMID- 27608597
TI - Specific combinations of presenilins and Aph1s affect the substrate specificity
and activity of gamma-secretase.
AB - The gamma-secretase complex comprises presenilin (PS), nicastrin (NCT), anterior
pharynx-defective 1 (Aph1), and presenilin enhancer 2 (Pen2). PS has two
homologues, PS1 and PS2. Aph1 has two isoforms, Aph1a and Aph1b, with the former
existing as two splice variants Aph1aL and Aph1aS. Each complex consists of one
subunit each, resulting in six different gamma-secretases. To better understand
the functional differences among the gamma-secretases, we reconstituted them
using a yeast system and compared Notch1-cleavage and amyloid precursor protein
(APP)-cleavage activities. Intriguingly, PS2/Aph1b had a clear substrate
specificity: APP-Gal4, but not Notch-Gal4, was cleaved. In HEK cell lines
expressing defined gamma-secretase subunits, we showed that PS1/Aph1b,
PS2/Aph1aL, PS2/Aph1aS and PS2/Aph1b gamma-secretase produced amyloid beta
peptide (Abeta) with a higher Abeta42+Abeta43-to-Abeta40 (Abeta42(43)/Abeta40)
ratio than the other gamma-secretases. In addition, PS2/Aph1aS gamma-secretase
produced less Notch intracellular domain (NICD) than did the other 5 gamma
secretases. Considering that the Abeta42(43)/Abeta40 ratio is relevant in the
pathogenesis of Alzheimer's disease (AD), and that inhibition of Notch cleavage
causes severe side effect, these results suggest that the PS2/Aph1aS gamma
secretase complex is a potential therapeutic target in AD.
PMID- 27608598
TI - Castration induced browning in subcutaneous white adipose tissue in male mice.
AB - We demonstrated that castration enhanced the expression of uncoupling protein 1
(Ucp1), a thermogenic protein, in brown adipose tissue (BAT) and subcutaneous
(sc) white adipose tissue (WAT) in male mice. Castration of male mice increased
body temperature and reduced body weight gain compared with those of sham
operated mice. BAT Ucp1 mRNA expression in castrated male mice was significantly
higher than that in sham-operated mice. Histologically, cells with multilocular
fat droplets were observed in the castrated inguinal scWAT. Immunohistochemical
staining revealed that these cells positively reacted with the anti-Ucp1
antibody. The Ucp1-positive area near the inguinal lymph node in the castrated
WAT was extensive compared with that of the sham-operated WAT. Castration-induced
Ucp1 up-regulation in scWAT was suppressed by high-fat diet feeding. These
findings suggest that thermogenesis by BAT activation and scWAT browning
contribute to castration-induced inhibition of body weight gain. However,
considering that the effect of castration was blunted by high-fat diet
consumption, thermogenesis stimulation in response to castration is inhibited by
chronic over-nutrition.
PMID- 27608599
TI - STING in tumor and host cells cooperatively work for NK cell-mediated tumor
growth retardation.
AB - An interferon-inducing DNA sensor STING participates in tumor rejection in mouse
models. Here we examined what mechanisms contribute to STING-dependent growth
retardation of B16 melanoma sublines by NK cells in vivo. The studies were
designed using WT and STING KO black mice, and B16D8 (an NK-sensitive melanoma
line having STING) and STING KO B16D8 sublines established for this study. The
results from tumor-implant studies suggested that STING in host immune cells and
tumor cells induced distinct profiles of chemokines including CXCL10, CCL5 and IL
33, and both participated in NK cell infiltration and activation in B16D8 tumor.
Spontaneous activation of STING occurs in host-immune and tumor cells of this NK
sensitive tumor, thereby B16D8 tumor growth being suppressed in this model. Our
data show that STING induces tumor cytotoxicity by NK cells through tumor and
host immune cell network to contribute to innate surveillance and suppression of
tumors in vivo.
PMID- 27608600
TI - Mechanisms of mortality in Culicoides biting midges due to Haemoproteus
infection.
AB - We examined the effects of Haemoproteus infection on the survival and pathology
caused in the biting midges. Forty-six females of Culicoides impunctatus were
exposed experimentally by allowing them to feed on a naturally infected red
backed shrike infected with Haemoproteus lanii (lineage hRB1, gametocytaemia
5.2%). Seventeen females were fed on an uninfected bird (controls). Dead insects
were collected, counted and used for dissection, histological examination and
polymerase chain reaction-based testing. Parasites were present in all
experimentally infected biting midges, but absent from control insects.
Survivorship differed significantly between the control and infected groups.
Twelve hours post-exposure (PE), 45 (98%) experimentally infected midges were
dead, but all control midges remained alive, and many of them survived until 7
day PE. The migrating ookinetes of H. lanii overfilled midgut, markedly damaged
the midgut wall, entered the haemocoel and overfilled the abdomen and thorax of
exposed biting midges. Massive infection by migrating ookinetes led to damage of
abdomen and thorax of biting midges. The parasites often present in large clumps
in the haemocoel in abdomen and thorax, leading to the interruption of the
haemolymph circulation. These are the main reasons for rapid death of biting
midges after feeding on high-intensity infections of Haemoproteus parasites.
PMID- 27608601
TI - Elucidating the neural correlates of related false memories using a systematic
measure of perceptual relatedness.
AB - Previous memory research has exploited the perceptual similarities between lures
and targets in order to evoke false memories. Nevertheless, while some studies
have attempted to use lures that are objectively more similar than others, no
study has systematically controlled for perceptual overlap between target and
lure items and its role in accounting for false alarm rates or the neural
processes underlying such perceptual false memories. The current study looked to
fill this gap in the literature by using a face-morphing program to
systematically control for the amount of perceptual overlap between lures and
targets. Our results converge with previous studies in finding a pattern of
differences between true and false memories. Most importantly, expanding upon
this work, parametric analyses showed false memory activity increases with
respect to the similarity between lures and targets within bilateral middle
temporal gyri and right medial prefrontal cortex (mPFC). Moreover, this pattern
of activation was unique to false memories and could not be accounted for by
relatedness alone. Connectivity analyses further find that activity in the mPFC
and left middle temporal gyrus co-vary, suggestive of gist-based monitoring
within the context of false memories. Interestingly, neither the MTL nor the
fusiform face area exhibited modulation as a function of target-lure relatedness.
Overall, these results provide insight into the processes underlying false
memories and further enhance our understanding of the role perceptual similarity
plays in supporting false memories.
PMID- 27608602
TI - Predicting early signs of dyslexia at a preliterate age by combining behavioral
assessment with structural MRI.
AB - BACKGROUND: Recent studies suggest that neurobiological anomalies are already
detectable in pre-school children with a family history of developmental dyslexia
(DD). However, there is a lack of longitudinal studies showing a direct link
between those differences at a preliterate age and the subsequent literacy
difficulties seen in school. It is also not clear whether the prediction of DD in
pre-school children can be significantly improved when considering
neurobiological predictors, compared to models based on behavioral literacy
precursors only. METHODS: We recruited 53 pre-reading children either with (N=25)
or without a family risk of DD (N=28). Quantitative T1 MNI data and literacy
precursor abilities were assessed at kindergarten age. A subsample of 35 children
was tested for literacy skills either one or two years later, that is, either in
first or second grade. RESULTS: The group comparison of quantitative T1 measures
revealed significantly higher T1 intensities in the left anterior arcuate
fascicle (AF), suggesting reduced myelin concentration in preliterate children at
risk of DD. A logistic regression showed that DD can be predicted significantly
better (p=.024) when neuroanatomical differences between groups are used as
predictors (80%) compared to a model based on behavioral predictors only (63%).
The Wald statistic confirmed that the T1 intensity of the left AF is a
statistically significant predictor of DD (p<.05). CONCLUSIONS: Our longitudinal
results provide evidence for the hypothesis that neuroanatomical anomalies in
children with a family risk of DD are related to subsequent problems in acquiring
literacy. Particularly, solid white matter organization in the left anterior
arcuate fascicle seems to play a pivotal role.
PMID- 27608604
TI - High-definition tDCS alters impulsivity in a baseline-dependent manner.
AB - In intertemporal choice (ITC), people discount future rewards in proportion to
the time delay until reward receipt. Despite recent non-invasive brain
stimulation studies suggesting a general causal link between dorsolateral
prefrontal cortex (dlPFC) activity and ITC impulsivity, results regarding the
functional specificity of dlPFC are mixed. We used high-definition transcranial
direct current stimulation (HD-tDCS) to map changes in causal impulsivity through
bi-directional modulation of left and right dlPFC during ITC. Model-free and
model-based analyses demonstrated that anodal and cathodal stimulation of left
dlPFC, but not right dlPFC, decreased and increased impulsivity, respectively.
Critically, an individual differences analysis revealed that modulation of
impulsivity was contingent on participants' baseline impulsivity. Overall, our
results might reconcile the discrepancies in the existing literature and suggest
a baseline-dependent role for left dlPFC during ITC.
PMID- 27608605
TI - Low energy electron imaging of domains and domain walls in magnesium-doped
lithium niobate.
AB - The understanding of domain structures, specifically domain walls, currently
attracts a significant attention in the field of (multi)-ferroic materials. In
this article, we analyze contrast formation in full field electron microscopy
applied to domains and domain walls in the uniaxial ferroelectric lithium
niobate, which presents a large 3.8 eV band gap and for which conductive domain
walls have been reported. We show that the transition from Mirror Electron
Microscopy (MEM - electrons reflected) to Low Energy Electron Microscopy (LEEM -
electrons backscattered) gives rise to a robust contrast between domains with
upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the
difference in surface potential between the domains. We demonstrate that out-of
focus conditions of imaging produce contrast inversion, due to image distortion
induced by charged surfaces, and also carry information on the polarization
direction in the domains. Finally, we show that the intensity profile at domain
walls provides experimental evidence for a local stray, lateral electric field.
PMID- 27608603
TI - Intracortical depth analyses of frequency-sensitive regions of human auditory
cortex using 7TfMRI.
AB - Despite recent advances in auditory neuroscience, the exact functional
organization of human auditory cortex (AC) has been difficult to investigate.
Here, using reversals of tonotopic gradients as the test case, we examined
whether human ACs can be more precisely mapped by avoiding signals caused by
large draining vessels near the pial surface, which bias blood-oxygen level
dependent (BOLD) signals away from the actual sites of neuronal activity. Using
ultra-high field (7T) fMRI and cortical depth analysis techniques previously
applied in visual cortices, we sampled 1mm isotropic voxels from different depths
of AC during narrow-band sound stimulation with biologically relevant temporal
patterns. At the group level, analyses that considered voxels from all cortical
depths, but excluded those intersecting the pial surface, showed (a) the greatest
statistical sensitivity in contrasts between activations to high vs. low
frequency sounds and (b) the highest inter-subject consistency of phase-encoded
continuous tonotopy mapping. Analyses based solely on voxels intersecting the
pial surface produced the least consistent group results, even when compared to
analyses based solely on voxels intersecting the white-matter surface where both
signal strength and within-subject statistical power are weakest. However, no
evidence was found for reduced within-subject reliability in analyses considering
the pial voxels only. Our group results could, thus, reflect improved inter
subject correspondence of high and low frequency gradients after the signals from
voxels near the pial surface are excluded. Using tonotopy analyses as the test
case, our results demonstrate that when the major physiological and anatomical
biases imparted by the vasculature are controlled, functional mapping of human
ACs becomes more consistent from subject to subject than previously thought.
PMID- 27608606
TI - Endocrine dysfunction following traumatic brain injury: a 5-year follow-up
nationwide-based study.
AB - Post-traumatic endocrine dysfunction is a complication of traumatic brain injury
(TBI). However, there is lack of long-term follow-up and large sample size
studies. This study included patients suffering from TBI registered in the Health
Insurance Database. Endocrine disorders were identified using the ICD codes: 244
(acquired hypothyroidism), 253 (pituitary dysfunction), 255 (disorders of the
adrenal glands), 258 (polyglandular dysfunction), and 259 (other endocrine
disorders) with at least three outpatient visits within 1 year or one admission
diagnosis. Overall, 156,945 insured subjects were included in the final analysis.
The 1- and 5-year incidence rates of post-traumatic endocrinopathies were 0.4%
and 2%, respectively. The risks of developing a common endocrinopathy (p < 0.001)
or pituitary dysfunction (P < 0.001) were significantly higher in patients with a
TBI history. Patients with a skull bone fracture had a higher risk of developing
pituitary dysfunction at the 1-year follow up (p value < 0.001). At the 5-year
follow up, the association between intracranial hemorrhage and pituitary
dysfunction (p value: 0.002) was significant. The risk of developing endocrine
dysfunction after TBI increased during the entire 5-year follow-up period. Skull
bone fracture and intracranial hemorrhage may be associated with short and long
term post-traumatic pituitary dysfunction, respectively.
PMID- 27608607
TI - Population analysis of clinical and environmental Vibrio parahaemolyticus
isolated from eastern provinces in China by removing the recombinant SNPs in the
MLST loci.
AB - Vibrio parahaemolyticus is a common seafood-borne pathogenic bacterium which
causes gastroenteritis in humans. Continuous surveillance on the molecular
characters of the clinical and environmental V. parahaemolyticus strains needs to
be conducted for the epidemiological and genetic purposes. To generate a picture
of the population distribution of V. parahaemolyticus in eastern China isolated
from clinical cases of gastroenteritis and environmental samples, we investigated
the genetic and evolutionary relationships of the strains using the commonly used
multi-locus sequence typing (MLST, in which seven house-keeping genes are used in
the protocol). A highly genetic diversity within the V. parahaemolyticus
population was observed but ST3 was still dominant in the clinical strains, and
103 new sequence types (ST) were found in the clinical strains by searching in
the global V. parahaemolyticus MLST database. With these genetically diverse
strains, we estimated the recombination rates of the loci in MLST analysis. The
locus recA was found to be subject to exceptionally high rate of recombination,
and the recombinant single nucleotide polymorphisms (SNPs) were also identified
within the seven loci. The phylogenetic tree of the strains was re-constructed
using the maximum likelihood method by removing the recombination SNPs of the
seven loci, and the minimum spanning tree was re-constructed with the six loci
without recA. Some changes were observed in comparison with the previously used
methods, suggesting that the homologous recombination has roles in shaping the
clonal structure of V. parahaemolyticus. We propose the recombination-free SNPs
strategy in the clonality analysis of V. parahaemolyticus, especially when using
the maximum likelihood method.
PMID- 27608608
TI - Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of
clinical experience.
AB - In the past three decades, we have learned much about the potential short-term
and long-term safety issues associated with the intravenous administration of
gadolinium based contrast agents (GBCAs). Yet, surprisingly, the past few years
and even months have been accompanied by new discoveries in this field. This
manuscript focuses predominantly on what we have learned - and are continuing to
learn - about the long-term potential MR safety issues associated with the
administration of the various GBCAs available today and will highlight areas in
which they appear to differ from each other at least in a quantitative fashion,
if not qualitatively.
PMID- 27608609
TI - Scoping review of health promotion and disease prevention interventions addressed
to elderly people.
AB - BACKGROUND: The ageing of modern societies remains one of the greatest challenges
for health and social systems. To respond to this challenge, we need effective
strategies assuring healthy active life for elderly people. Health promotion and
related activities are perceived as a key intervention, which can improve
wellbeing in later life. The main aim of this study is the identification and
classification of such interventions addressed to older adults and elderly.
Therefore, the strategy based on the scoping review as a feasible tool for
exploring this domain, summarizing research findings and identifying gaps of
evidence, was applied. METHODS: The scoping review relies on the analysis of
previous reviews of interventions aimed at older adults (55-64 years old) and
elderly persons (65 years and above) assessed for their effectiveness in the
framework of a systematic review and/or meta-analysis. The search strategy was
based on the identification of interventions reported as health promotion,
primary disease prevention, screening or social support. In the analysis, the
reviews published from January 2000 to April 2015 were included. RESULTS: The
search strategy yielded 334 systematic reviews and/or meta-analyses addressed to
target groups of interest, 182 of them assessed interventions belonging to health
promotion, 219 to primary prevention, 34 to screening and 35 to social support.
The studies focused on elderly (65 years and above) made up 40.4 % of all
retrieved reviews and those addressing population of 55 years and above accounted
for 24.0 %. CONCLUSIONS: Interventions focused on health maintenance and
improvement in elderly and older adults represent frequently combined health
promotion and disease prevention actions. Many interventions of this type are not
addressed exclusively to elderly populations and/or older adults but are designed
for the general population. The most common types of interventions addressed to
elderly and older adults in the area of health promotion include health
education, behavior modification and health communication.
PMID- 27608610
TI - Combination of Fenton processes and biotreatment for wastewater treatment and
soil remediation.
AB - There is a continuously increasing worldwide concern for the development of
wastewater and contaminated soil treatment technologies. Fenton processes and
biological treatments have long been used as common technologies for treating
wastewater and polluted soil but they still need to be modified because of some
defects (high costs of Fenton process and long remediation time of
biotreatments). This work first briefly introduced the Fenton technology and
biotreatment, and then discussed the main considerations in the construction of a
combined system. This review shows a critical overview of recent researches
combining Fenton processes (as pre-treatment or post-treatment) with
bioremediation for treatment of wastewater or polluted soil. We concluded that
the combined treatment can be regarded as a novel and competitive technology.
Furthermore, the outlook for potential applications of this combination in
different polluted soil and wastewater, as well as the mechanism of combination
was also discussed.
PMID- 27608611
TI - Dopamine-independent effects of combining transcranial direct current stimulation
with cued gait training on cortical excitability and functional mobility in
Parkinson's disease.
AB - OBJECTIVE: To investigate the dopamine-dependent effect of combining transcranial
direct current stimulation (tDCS) with visually cued gait training on cortical
excitability and functional mobility in individuals with Parkinson's disease.
DESIGN: A pilot, randomized, double-blind, controlled trial. METHODS: Twenty-two
patients with Parkinson's disease were randomly assigned to 2 groups: (i) active
anodal tDCS over the supplementary motor area (experimental group), or (ii) sham
tDCS (control group). After tDCS, both groups participated in a visually cued
gait training. Functional mobility was evaluated with the Timed Up and Go test
(TUG). Cortical excitability was assessed by active motor threshold and motor
evoked potential amplitudes elicited by transcranial magnetic stimulation in
patients in on and off medication states. RESULTS: In the TUG test both groups
achieved improvements either in on or off medication condition compared with
baseline. However, for both medication conditions, these gains were maintained
only in the experimental group during 1-month follow-up, compared with baseline.
In the experimental group, enhancement of cortical excitability was observed at
post-intervention and 1-month follow-up (both only for the "on" phase) compared
with baseline. CONCLUSION: These findings suggest that tDCS, independent of
dopaminergic medication state, might prolong the positive effect induced by cued
gait training on functional mobility.
PMID- 27608612
TI - MiR 3180-5p promotes proliferation in human bladder smooth muscle cell by
targeting PODN under hydrodynamic pressure.
AB - Human bladder smooth muscle cells (HBSMCs) were subjected to pressure cycles of
up to 200 cm H2O to a pressure of 0 cm H2O for 24 hours. The total RNA extracted
from each group was subjected to microarray analysis. miR-3180-5p emerged as the
most overexpressed of all the differentially expressed microRNAs, and this
finding was validated by PCR. We then used CCK-8 to quantify cell proliferation
after liposome-mediated transfection. Subsequently, we investigated the change in
PODN and its downstream signaling proteins, including cyclin-dependent kinase 2
(cdk2) and p21. In addition, flow cytometry was performed to quantify cell-cycle
distribution. The results show that miR-3180-5p, the microRNA that was most
overexpressed in response to HP, reduced the expression of PODN and podocan (p =
0.004 and p = 0.041, respectively). Silencing of PODN via miR-3180-5p
overexpression revealed a significant promotion of cell proliferation increased
in the CCK-8 experiment, p = 0.00077). This cell proliferation was accompanied by
an increase in cdk2 expression (p = 0.00193) and a decrease in p21 expression (p
= 0.0095). The percentage of cells in (S + G2/M) improved after transfection (p =
0.002). It was apparent that HP upregulates miR-3180-5p, which inhibits the
expression of PODN and promotes HBSMC proliferation via the cdk2 signaling
pathway.
PMID- 27608613
TI - A comparative study between the effect of 17-beta estradiol and angiotensin
converting enzyme inhibitor on osteoporosis in ovariectomized rats.
AB - Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand
(RANKL) have been revealed in the pathogenesis of primary osteoporosis and other
metabolic bone diseases. This study was designed to assess the effect of 17-beta
estradiol (E2) treatment and angiotensin converting enzyme inhibitor (ACEI),
captopril, on osteoporosis induced by ovariectomy in rats and discussing the role
of OPG/RANKL ratio in their action. Thirty two adult female rats were divided
into four equal groups. Group I: control group, Group II: ovariectomized (OVX)
non treated group, Group III: OVX rats treated with E2, Group IV: OVX rats
treated with captopril. OVX rats showed a significant decrease in serum Ca2+ and
OPG levels with significant increase in serum RANKL, osteocalcin, alkaline
phosphatase activity and urinary hydroxyproline levels. Treatment with captopril
as well as E2 led to a significant improvement in bone markers levels with a
significant increase in OPG/RANKL ratio. Image analysis technique revealed that
there was a significant improvement in cortical bone thickness (CBT) and mean
trabecular bone density (TBD) in OVX rats treated with either E2 or ACEI. So, we
can conclude that the protective effect of E2 and ACEI on osteoporosis may be
mediated by influencing OPG/RANKL signaling.
PMID- 27608614
TI - Swimming training affects apoptosis-related microRNAs and reduces cardiac
apoptosis in mice.
AB - We sought to investigate effects of exercise training on apoptosis-related
microRNAs (miRs) and their validated targets, discussing molecular mechanism of
the exercise-induced benefit in heart. Male C57BL/6 mice were randomly assigned
to three groups: sedentary (SE), exercise training 1 (ET1) and exercise training
2 (ET2). ET1 swam for 8 weeks, once a day and 5 days per week with incremental
load. ET2 performed the same work as ET1 and switched to twice a day by the end
of the 5th week. In ET2, positive cell rate (%) tested by TUNEL assay decreased
significantly (p < 0.05), and the load decreased miR-1 level by 29% (p < 0.01),
also increased miR-30b and miR-21 levels by 32% (p < 0.01) and 18% (p < 0.05)
respectively. In addition, Bcl-2 expression was increased by 98% (p < 0.01). p53,
PDCD4 and Drp-1 expressions were decreased by 45% (p < 0.01), 6% (p > 0.05) and
36% (p < 0.01) respectively, compared with SE. In ET1, only miR-30b level was
increased by 22% (p < 0.05) with a 48% decrease in p53 level (p < 0.01). Both
swimming groups increased Bcl-2/Bax ratio significantly (p < 0.01). This study
indicated that apoptosis-related miRs and their downstream proteins in heart can
be influenced by swimming training that may be responsible for the exercise
induced cardioprotection.
PMID- 27608615
TI - Influance of regular swimming on serum levels of CRP, IL-6, TNF-alpha in high-fat
diet-induced type 2 diabetic rats.
AB - Due to key role of inflammation in pathogenesis of type 2 diabetes mellitus
(T2DM), aim of this study was evaluating the influance of regular swimming on
serum levels of C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis
factor-alpha (TNF-alpha) in high-fat diet-induced diabetic rats. Fourty male
Wistar rats were randomly divided into control, diabetic, exercise and diabetic
exercise groups (n = 10). Diabetes was induced by high-fat diet and
streptozotocin (35 mg/kg, i.p.). In exercise groups, after induction of diabetes,
animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the
end of training, rats were anestatized and blood samples and pancreatic tissues
were collected and used for evaluation of CRP, IL-6, TNF-alpha and pancreatic
histopatholology. Our results showed significantly increase in lymphocytes,
monocytes and decrease in neutrophils in diabetic rats (p < 0.01), which these
parameters significantly reversed to control levels by induction of swimming (p <
0.01). In diabetic group, the levels of CRP, IL-6 and TNF-alpha increased (p <
0.01), and swimming decreased these factors significantly. Histopathological
results of this study also showed that swimming can prevent damage induced by
diabetes. The present study indicates that swim training is associated with
improved inflammation and inflammatory mediators and pancreatic damage.
PMID- 27608616
TI - Ultrastructural remodelling of slow skeletal muscle fibres in creatine kinase
deficient mice: a quantitative study.
AB - Creatine kinase content, isoform distribution, and participation in energy
transfer are muscle type specific. We analysed ultrastructural changes in slow
muscle fibres of soleus due to invalidation of creatine kinase (CK) to reveal a
difference in the remodelling strategy in comparison with fast muscle fibres of
gastrocnemius published previously. We have employed the stereological method of
vertical sections and electron microscopy of soleus muscles of wild type (WT) and
CK-/- mice. The mitochondrial volume density was 1.4* higher but that of
sarcoplasmic reticulum (SR) was almost 5* lower in slow CK-/- muscles fibres than
in WT fibres. The volume density of terminal cisterns and of t-tubules was also
lower in CK-/- than in WT fibres. The analysis of organelle environment revealed
increased neighbourhood of mitochondria and A-bands that resulted from the
decreased volume density of SR, from relocation of mitochondria along myofibrils,
and from intrusion of mitochondria to myofibrils. These processes direct ATP
supply closer to the contractile machinery. The decreased interaction between
mitochondria and SR suggests reduced dependence of calcium uptake on oxidative
ATP production. In conclusion, the architecture of skeletal muscle cells is under
control of a cellular program that optimizes energy utilization specifically for
a given muscle type.
PMID- 27608617
TI - High-resolution separation performance of poly(caprolactone)diol for challenging
isomers of xylenes, phenols and anilines by capillary gas chromatography.
AB - Efficient separation of xylenes, phenols and anilines is a big issue in chemical
and petroleum industries. This work presents the first example of employing poly
(caprolactone) diol (PCL-Diol) as stationary phase for high-resolution gas
chromatographic (GC) separations of these tough isomer mixtures. It showed medium
polarity and stronger H-bonding basicity than H-bonding acidity. Impressively,
PCL-Diol column exhibited extremely high resolving capability for the isomer
mixtures of xylenes, cresols/xylenols, and toluidines/xylidines with good peak
shapes. Moreover, it exhibited preferential retention for analytes of a linear
alkyl chain, suggesting its shape fitting selectivity for specific analytes. In
addition, its separation performance has good repeatability with RSD values on
retention times below 0.01% for run to run (n=6), 0.67-0.80% for day to day (n=4)
and 3.2-4.4% for column to column (n=4) repeatability, respectively. Furthermore,
it was applied for the determination of isomer impurities in real samples,
showing good potential for practical use. This work demonstrates the advantageous
high-resolution separation performance for challenging isomers and shows its
promising future of PCL-Diol-based materials in separation science.
PMID- 27608618
TI - Cyclic peptide ligand with high binding capacity for affinity purification of
immunoglobulin G.
AB - The rapidly increasing implementation of antibodies in therapeutic and diagnostic
applications has necessitated the development of antibody production and
purification technologies for both academic and industrial usage. Bacterial
Protein A and Protein G are known to bind antibodies with high affinity and have
facilitated the isolation and purification thereof. Recently, small peptide
ligands (i.e. IgG Fc domain-binding peptides, FcBP) that specifically bind to the
Fc-domain of antibodies were reported. In the present study we describe the
development of a reusable high affinity column for antibody purification
utilizing immobilized FcBP, comprising 13 amino acids residues, on a sepharose
resin. In addition to FcBP, Cys to Ser substituted FcBP (FcBP-Ser), reduced FcBP
(FcBP-Red), commercial Protein A and Protein G resins, packed into columns, were
evaluated for antibody purification. All these columns except the FcBP-Ser one
showed good binding capacity for a humanized IgG (trastuzumab) and a chimeric IgG
(cetuximab). The column packed with FcBP-Red allowed antibody purification at a
less acidic pH (pH 4.8) than was required for the other ligand affinity columns
used in our experiments (i.e., pH 3.2 for Protein G and FcBP columns, and pH 3.5
for Protein A column, respectively). Utilizing the FcBP column, antibodies from
swine human sera were isolated with a purity of 95%. Interestingly, the FcBP
column could be easily regenerated and operated without loss of efficiency for up
to 60 runs, the maximum number of runs performed in the present study.
PMID- 27608619
TI - Schinus terebinthifolius countercurrent chromatography (Part II): Intra-apparatus
scale-up and inter-apparatus method transfer.
AB - Countercurrent chromatography (CCC) is being widely used across the world for
purification of various materials, especially in natural product research. The
predictability of CCC scale-up has been successfully demonstrated using specially
designed instruments of the same manufacturer. The reality is that the most of
CCC users do not have access to such instruments and do not have enough
experience to transfer methods from one CCC column to another. This unique study
of three international teams is based on innovative approach to simplify the
scale-up between different CCC machines using fractionation of Schinus
terebinthifolius berries dichloromethane extract as a case study. The optimized
separation methodology, recently developed by the authors (Part I), was
repeatedly performed on CCC columns of different design available at most
research laboratories across the world. Hexane - ethyl acetate - methanol - water
(6:1:6:1, v/v/v/v) was used as solvent system with masticadienonic and 3beta
masticadienolic acids as target compounds to monitor stationary phase retention
and calculate peak resolution. It has been demonstrated that volumetric, linear
and length scale-up transfer factors based on column characteristics can be
directly applied to different i.d., volume and length columns independently on
instrument make in an intra-apparatus scale-up and inter-apparatus method
transfer.
PMID- 27608620
TI - Cognitive change is more positively associated with an active lifestyle than with
training interventions in older adults at risk of dementia: a controlled
interventional clinical trial.
AB - BACKGROUND: While observational studies show that an active lifestyle including
cognitive, physical, and social activities is associated with a reduced risk of
cognitive decline and dementia, experimental evidence from corresponding training
interventions is more inconsistent with less pronounced effects. The aim of this
study was to evaluate and compare training- and lifestyle-related changes in
cognition. This is the first study investigating these associations within the
same time period and sample. METHODS: Fifty-four older adults at risk of dementia
were assigned to 10 weeks of physical training, cognitive training, or a matched
wait-list control condition. Lifestyle was operationalized as the variety of self
reported cognitive, physical, and social activities before study participation.
Cognitive performance was assessed with an extensive test battery prior to and
after the intervention period as well as at a 3-month follow-up. Composite
cognition measures were obtained by means of a principal component analysis.
Training- and lifestyle-related changes in cognition were analyzed using linear
mixed effects models. The strength of their association was compared with paired
t-tests. RESULTS: Neither training intervention improved global cognition in
comparison to the control group (p = .08). In contrast, self-reported lifestyle
was positively associated with benefits in global cognition (p < .001) and
specifically in memory (p < .001). Moreover, the association of an active
lifestyle with cognitive change was significantly stronger than the benefits of
the training interventions with respect to global cognition (ps < .001) and
memory (ps < .001). CONCLUSIONS: The associations of an active lifestyle with
cognitive change over time in a dementia risk group were stronger than the
effects of short-term, specific training interventions. An active lifestyle may
differ from training interventions in dosage and variety of activities as well as
intrinsic motivation and enjoyment. These factors might be crucial for designing
novel interventions, which are more efficient than currently available training
interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01061489 .
Registered February 2, 2010.
PMID- 27608622
TI - Erratum to: 'Modified transesophageal echocardiography of the dissected thoracic
aorta; a novel diagnostic approach'.
PMID- 27608621
TI - The effects of a mindfulness-based lifestyle program for adults with Parkinson's
disease: a mixed methods, wait list controlled randomised control study.
AB - BACKGROUND: Parkinson's disease (PD) is the second commonest neurodegenerative
disease in developed countries. Current treatment for PD is pharmacologically
focused and can have significant side-effects. There is increasing interest in
holistic approaches including mindfulness to help manage the challenges
associated with living with PD. We hypothesised that there would be an
improvement in PD associated function and wellbeing in participants after
participating in a 6-week mindfulness-based lifestyle program, and that these
improvements would be sustainable at 6 months. Our primary objective was to
determine changes in function and wellbeing associated with PD. METHODS: An
exploratory prospective, mixed-method, randomised control trial incorporating a
before and after design with a waitlist control, with an embedded qualitative
component was conducted in 2012-2013. Participants included community living
adults with disability congruent to H&Y Stage 2 PD, aged 18-75, fluent in spoken
and written English and able to attend at least four of six sessions of the
program. Participants were randomised to the intervention or wait-list control
groups at two locations. All participants in the wait-list control group
eventually received the intervention. Two randomisation codes were created for
each location. Allocation to the intervention or wait-list control was by random
number generation. The program facilitator and participants were blinded to
participant data. RESULTS: Group 1 included 35 participants and group 2 (the
waitlist control), 37. Data was analysed from 24 (group 1) and 33 (group 2)
participants. The intervention group, compared to the waitlist control, showed a
small improvement in function and wellbeing associated with PD immediately after
the program (t-score = -0.59) and at 6-month post intervention (t-score = -1.42)
as reported by the PDQ-39 SI. However this finding was not significant (p = 0.56
and 0.16 respectively). A small yet significant effect size (beta = 0.23) in PDQ
39 ADL was reported in group 1 after 6-months post-intervention. This showed a
positive improvement in the ADL as reported by group 1 after 6-months (t-score
1.8, p = 0.04). Four secondary measures are reported. CONCLUSIONS: Our findings
suggest mindfulness-based lifestyle programs have potential to assist
participants in managing the ongoing difficulties associated with a neurological
condition such as Parkinson's disease. Importantly, our study shows promise for
the long term benefits of such programs. Improvements to participant activities
in daily living and mindfulness were retained at 6-months post intervention. A
more definitive study should be conducted in a larger sample of PD patients to
further explore these findings and their impact on reducing stress and anxiety in
PD patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
(ANZCTR) ACTRN12612000440820 , 17(th) April 2012.
PMID- 27608623
TI - MicroRNAs in acute kidney injury.
AB - Acute kidney injury (AKI) is an important clinical issue that is associated with
significant morbidity and mortality. Despite research advances over the past
decades, the complex pathophysiology of AKI is not fully understood. The
regulatory mechanisms underlying post-AKI repair and fibrosis have not been
clarified either. Furthermore, there is no definitively effective treatment for
AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23
nucleotides that have been shown to be crucial to the post-transcriptional
regulation of various cellular biological functions, including proliferation,
differentiation, metabolism, and apoptosis. In addition to being fundamental to
normal development and physiology, miRNAs also play important roles in various
human diseases. In AKI, some miRNAs appear to act pathogenically by promoting
inflammation, apoptosis, and fibrosis, while others may act protectively by
exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenic
effects. Thus, miRNAs have not only emerged as novel biomarkers for AKI; they
also hold promise to be potential therapeutic targets.
PMID- 27608624
TI - Effects of a home-based activation intervention on self-management adherence and
readmission in rural heart failure patients: the PATCH randomized controlled
trial.
AB - BACKGROUND: Heart failure (HF) patients discharged from rural hospitals have
higher 30-day readmission rates. Self-management (SM) reduces readmissions, but
adherence to SM guidelines is low in the rural HF population. We tested a home
based intervention to enhance patient activation and lead to improved SM
adherence. METHODS: In this two-group, repeated measures randomized control
trial, the main outcomes were patient reported and clinical outcomes associated
with SM adherence, and all-cause readmission at 30, 90 and 180 days. RESULTS: The
study included 100 HF patients discharged from a rural critical access hospital.
The intervention group received a 12-week SM training and coaching program
delivered by telephone and tailored on subjects' activation levels. At alpha =
.10, the PATCH intervention showed significantly greater improvement compared to
usual care in patient-reported SM adherence: weighing themselves, following a low
sodium diet, taking prescribed medication, and exercising daily (all p < .0005)
at 3 and 6 months after discharge. In contrast, groups did not differ in physical
activity assessed by actigraphy or in clinical biomarkers. Contrary to
expectation, the 30-day readmission rate was significantly higher (p = .088) in
the intervention group (19.6 %) than in the control group (6.1 %), with no
differences at 90 or 180 days. CONCLUSION: It is feasible to conduct a randomized
controlled trial in HF patients discharged from rural critical access hospitals.
Significantly higher patient-reported SM adherence was not accompanied by lower
clinical biomarkers or readmission rates. Further research is needed to
understand mechanisms that influence outcomes and healthcare utilization in this
population. TRIAL REGISTRATION: CLINICAL TRIAL REGISTRATION INFORMATION:
ClinicalTrials.gov; NCT01964053 .
PMID- 27608625
TI - Network Analysis of Fine Particulate Matter (PM2.5) Emissions in China.
AB - Specification of PM2.5 spatial and temporal characteristics is important for
understanding PM2.5 adverse effects and policymaking. We applied network analysis
to studying the dataset MIX, which contains PM2.5 emissions recorded from 2168
monitoring stations in China in 2008 and 2010. The results showed that for PM2.5
emissions from industrial sector 8 clusters were found in 2008 but they merged
together into a huge cluster in 2010, suggesting that industrial sector underwent
an integrating process. For PM2.5 emissions from electricity generation sector,
strong locality of clusters was revealed, implying that each region had its own
electricity generation system. For PM2.5 emissions from residential sector, the
same pattern of 10 clusters was uncovered in both years, implicating the
household energy consumption unchanged from 2008 to 2010. For PM2.5 emissions
from transportation sector, the same pattern of 5 clusters with many connections
in-between was unraveled, indicating the high-speed development of transportation
nationalwidely. Except for the known elements, mercury (Hg) surfaced as an
element for particle nucleation. To our knowledge, this is the first network
study in this field.
PMID- 27608627
TI - The Autographa californica multiple nucleopolyhedrovirus Ac132 plays a role in
nuclear entry.
AB - A recent study found that the Autographa californica multiple
nucleopolyhedrovirus (AcMNPV) Ac132 is a nucleocapsid-associated protein and
required for budded virion (BV) production. We therefore initiated experiments
aimed at understanding how Ac132 is involved in AcMNPV infection. An 80 bp region
of ac132 was replaced with a chloramphenicol resistance gene to construct
vAc132KO. Transfection of vAc132KO into Sf9 cells resulted in a single-cell
infection phenotype, consistent with findings reported in a previous study.
Interestingly, BVs were observable in the supernatants, and the BV production in
the supernatant was comparable with that present in supernatants from a WT
control. These results suggest that the ac132 deletion does not affect the egress
of nucleocapsids from the transfected cells to form BVs, but the BVs are non
infectious. Transfection with DNA extracted from vAc132KO BVs could establish
infection in Sf9 cells, indicating that the deletion does not affect the
integrity of the viral genomic DNA in non-infectious progeny BVs. To monitor the
traffic of nucleocapsids without Ac132, two mCherry proteins were fused with the
major capsid protein VP39 to construct vAc132KO : 2mC. Using confocal microscopy,
we observed that the nucleocapsids of vAc132KO : 2mC could not enter the nucleus
and instead remained docked at the nuclear membrane. This study provides a new
understanding of the nuclear entry of baculoviruses.
PMID- 27608626
TI - Ankle impingement.
AB - Ankle impingement is a syndrome that encompasses a wide range of anterior and
posterior joint pathology involving both osseous and soft tissue abnormalities.
In this review, the etiology, pathoanatomy, diagnostic workup, and treatment
options for both anterior and posterior ankle impingement syndromes are
discussed.
PMID- 27608629
TI - The LUNG SAFE study: a presentation of the prevalence of ARDS according to the
Berlin Definition!
PMID- 27608628
TI - Evidence of dipstick superiority over urine microscopy analysis for detection of
hematuria.
AB - BACKGROUND: There is an unresolved debate on the best screening method for
hematuria as a symptom of glomerulonephritis or urological malignancies. The
urinary dipstick is generally considered as an imperfect surrogate for urine
microscopy analysis. RESULTS: We designed a study to compare urine microscopy
analysis, urinary dipstick and flow cytometry, using controlled dilutions of
blood in urine samples from volunteers collected in two different physiologically
relevant conditions (basal state and hyperhydration). We found that although all
techniques were 100 % effective in detecting hematuria at basal state, these
results were variably reproduced when testing the same final amount of hematuria
in urine collected after hyperhydration. Our data shows a variable sensitivity
for the detection of hematuria by urine microscopy analysis or flow cytometry,
but not by urinary dipstick. CONCLUSIONS: Urinary dipstick qualifies as a better
screening test for hematuria than urine microscopy analysis or flow cytometry, as
it is sensitive and performs better in unstandardized conditions. It is
universally available and also faster and cheaper than cytometric techniques.
PMID- 27608631
TI - Erratum to: 'Comparison of calculated and experimental power in maximal lactate
steady state during cycling'.
PMID- 27608630
TI - Erratum to: An ancient genome duplication contributed to the abundance of
metabolic genes in the moss Physcomitrella patens.
PMID- 27608633
TI - Comparative nitrogen use efficiency of urea and pig slurry for regrowth yield and
nutritive value in perennial ryegrass sward.
AB - OBJECTIVE: The study aimed to assess the N use efficiency (NUE) of pig slurry (in
comparison with chemical fertilizer) for each regrowth yield and annual herbage
production and their nutritive value. METHODS: Consecutive field experiments were
separately performed using a single application with a full dose of N (200 kg
N/ha) in 2014 and by four split applications in 2015 in different sites. The
experiment consisted of three treatments: i) control plots that received no
additional N, ii) chemical fertilizer-N as urea, and iii) pig-slurry-N with five
replicates. RESULTS: The effect of N fertilization on herbage yield, N recovery
in herbage, residual inorganic N in soil, and crude protein were significantly
positive. When comparing the NUE between the two N sources (urea and pig slurry),
pig slurry was significantly less effective for the earlier two regrowth periods,
as shown by lower regrowth dry matter (DM) yield, N amount recovered in herbage,
and inorganic N availability in soil at the 1st and 2nd cut compared to those of
urea-applied plots. However, the effect of split application of the two N sources
was significantly positive at the last two regrowth periods (at the 3rd and 4th
cut). The two N sources and/or split application had little or no influence on
neutral detergent fiber (NDF) content, acid detergent fiber (ADF) content, and in
vitro DM digestibility, whereas cutting date was a large source of variation for
these variables, resulting in a significant increase in in vitro DM digestibility
for the last two regrowth periods when an increase in NDF and ADF content
occurred. Split application of N reduced the N loss via nitrate leaching by 36%
on average for the two N sources compared to a single application. CONCLUSION:
The pig slurry-N was utilized as efficiently as urea-N for annual herbage yield,
with a significant increase in NUE especially for the latter regrowth periods.
PMID- 27608632
TI - Humoral and cellular immune responses in mice against secreted and somatic
antigens from a Corynebacterium pseudotuberculosis attenuated strain: Immune
response against a C. pseudotuberculosis strain.
AB - BACKGROUND: Corynebacterium pseudotuberculosis is the etiologic agent of caseous
lymphadenitis (CL), a chronic disease that affects goats and sheep. CL is
characterized by the formation of granulomas in lymph nodes and other organs,
such as the lungs and liver. Current knowledge of CL pathogenesis indicates that
the induction of humoral and cellular immune responses are fundamental to disease
control. The aim of this study was to evaluate the humoral and cellular immune
responses in BALB/c mice inoculated with a C. pseudotuberculosis strain isolated
in the state of Bahia, Brazil. RESULTS: The lymphocyte proliferation and in vitro
production of IFN-gamma, IL-4, IL-10, IL-12 and nitric oxide by spleen cells
stimulated with secreted and somatic antigens from the studied strain were
evaluated. IgG subclasses were also analyzed. Results showed a significant
increase of Th1-profile cytokines after 60 days post-inoculation, as well as an
important humoral response, represented by high levels of IgG2a and IgG1 against
C. pseudotuberculosis. CONCLUSION: The T1 strain of C. pseudotuberculosis was
shown to induce humoral and cellular immune responses in BALB/c mice, but, even
at a dosage of 1x10(7) CFU, no signs of the disease were observed.
PMID- 27608634
TI - Effect of dietary protein sources on production performance, egg quality, and
plasma parameters of laying hens.
AB - OBJECTIVE: This study was conducted to evaluate the effects of dietary protein
sources (soybean meal, SBM; low-gossypol cottonseed meal, LCSM; double-zero
rapeseed meal, DRM) on laying performance, egg quality, and plasma parameters of
laying hens. METHODS: A total of 432 32-wk-old laying hens were randomly divided
into 6 treatments with 6 replicates of 12 birds each. The birds were fed diets
containing SBM, LCSM100, or DRM100 individually or in combination with an equal
amount of crude protein (CP) (LCSM50, DRM50, and LCSM50-DRM50). The experimental
diets, which were isocaloric (metabolizable energy, 11.11 MJ/kg) and
isonitrogenous (CP, 16.5%), had similar digestible amino acid profile. The
feeding trial lasted 12 weeks. RESULTS: The daily egg mass was decreased in the
LCSM100 and LCSM50-DRM50 groups (p<0.05) in weeks 41 to 44. The LCSM50 group did
not affect egg production compared to the SBM group in weeks 41 to 44 (p>0.05)
and showed increased yolk color at the end of the trial (p<0.05). Compared to the
SBM group, the LCSM100 and LCSM50-DRM50 groups showed decreased albumen weight
(p<0.05), CP weight in the albumen (p<0.05) and CP weight in the whole egg
(p<0.05) at 44 weeks. Plasma total protein (TP) levels were lower in the LCSM100
group than in the SBM group at 44 weeks (p<0.05); however, TP, albumin, and
globulin levels were not significantly different between the LCSM50 group and the
SBM group or between the DRM50 group and the SBM group (p>0.05). CONCLUSION:
Together, our results suggest that the LCSM100 or DRM100 diets may produce the
adverse effects on laying performance and egg quality after feeding for 8 more
weeks. The 100.0 g/kg LCSM diet or the148.7 g/kg DRM diet has no adverse effects
on laying performance and egg quality.
PMID- 27608635
TI - Nutrient intake, digestibility and performance of Gaddi kids supplemented with
tea seed or tea seed saponin extract.
AB - OBJECTIVE: An experiment was conducted to determine the nutrient intake,
digestibility, microbial protein synthesis, haemato-biochemical attributes,
immune response and growth performance of Gaddi kids fed with oat fodder based
basal diet supplemented with either tea seed or tea seed saponin (TSS) extract.
METHODS: Eighteen male kids, 7.03+/-0.16 months of age and 19.72+/-0.64 kg body
weight, were distributed into three groups, T0 (control), T1, and T2, consisting
of 6 animals each in a completely randomized design. The kids were fed a basal
diet consisting of concentrate mixture and oat fodder (50:50). Animals in group
III (T2) were supplemented with TSS at 0.4% of dry matter intake (DMI), and group
II (T1) were supplemented with tea seed at 2.6% of DMI to provide equivalent dose
of TSS as in T2. Two metabolism trials were conducted, 1st after 21 days and 2nd
after 90 days of feeding to evaluate the short term and long term effects of
supplementation. RESULTS: The tea seed (T1) or TSS (T2) supplementation did not
affect DMI as well as the digestibility of dry matter, organic matter, crude
protein, neutral detergent fibre, and acid detergent fibre. Nutritive value of
diet and plane of nutrition were also comparable for both the periods. However,
the average daily gain and feed conversion ratio (FCR) were improved (p<0.05) for
T1 and T2 as compared to T0. The microbial protein supply was also higher
(p<0.05) for T1 and T2 for both the periods. There was no effect of
supplementation on most blood parameters. However, the triglyceride and low
density lipoprotein cholesterol levels decreased (p<0.05) and high density
lipoprotein-cholesterol level increased (p<0.05) in T2 as compared with T0 and
T1. Supplementation also did not affect the cell mediated and humoral immune
response in goats. CONCLUSION: Tea seed at 2.6% of DMI and TSS at 0.4% DMI can be
fed to Gaddi goats to improve growth rate, FCR and microbial protein synthesis.
PMID- 27608636
TI - Identification and characterization of novel single nucleotide polymorphism
markers for fat deposition in muscle tissue of pigs using amplified fragment
length polymorphism.
AB - OBJECTIVE: This study was conducted to identify and evaluate the effective single
nucleotide polymorphism (SNP) markers for fat deposition in the longissimus dorsi
muscles of pigs using the amplified fragment length polymorphism (AFLP) approach.
METHODS: Sixty-four selective primer combinations were used to identify the AFLP
markers in the 20 highest- and 20 lowest-intramuscular fat (IMF) content
phenotypes. Five AFLP fragments were converted into simple codominant SNP
markers. These SNP markers were tested in terms of their association with IMF
content and fatty acid (FA) composition traits in 620 commercially crossbred
pigs. RESULTS: The SSC7 g.4937240C>G marker showed an association with IMF
content (p<0.05). The SSC9 g.5496647_5496662insdel marker showed a significant
association with IMF content and arachidonic levels (p<0.05). The SSC10
g.71225134G>A marker revealed an association with palmitoleic and omega9 FA
levels (p<0.05), while the SSC17 g.61976696G>T marker showed a significant
association with IMF content and FA levels of palmitoleic, eicosenoic,
arachidonic, monounsaturated fatty acids, and omega9 FA levels. However, no
significant association of SSC8 g.47338181G>A was observed with any IMF and FA
levels in this study. CONCLUSION: Four SNP markers (SSC7 g.4937240C>G, SSC9
g.5496647_5496662insdel, SSC10 g.71225134G>A, and SSC17 g.61976696G>T) were found
to be associated with IMF and/or FA content traits in commercially crossbred
pigs. These findings provide evidence of the novel SNP markers as being
potentially useful for selecting pigs with the desirable IMF content and FA
composition.
PMID- 27608637
TI - Effect of fibrous diets on chemical composition and odours from pig slurry.
AB - OBJECTIVE: Incorporating high fibre ingredients into pig diets has the potential
to reduce odour emissions from of pigs. The current study was carried out to
determine effect of diets containing 0, 80 and 160 g/kg of each of lucerne hay,
maize cobs and sunflower husks on the chemical characteristics and odours from
pig slurries. METHODS: Twenty eight pigs averaging 18+/-2.0 kg were kept in
individual cages, over four weeks. All pigs were fed ad libitum. Faeces and urine
were collected, mixed in a 1:2.3 ratio (w/w), stored and fermented for 16 days in
a temperature controlled room at 22 degrees C+/-2.3 degrees C. The slurry was
sampled twice (on day 1 and on day 16) of the fermentation period and analysed
for pH, chemical oxygen demand (COD), nitrogen and short chain fatty acids (SCFA)
concentration, on wet basis. All samples were tested for odour offensiveness
using 18 panelists. A scale of 1 to 5 was used to rank the odour severity, (1 =
not offensive, 5 = extremely offensive). RESULTS: Slurry pH and COD varied with
fibre source (p<0.05). On day 16, COD for lucerne hay, sunflower husk and maize
cobs were 369, 512, and 425 (standard error of the mean = 34.2) mg of oxygen per
litre. Total SCFA concentration was higher at day 16 than day 1 (p< 0.05). Odour
offensiveness varied with fibre source across both incubation periods (p<0.05).
Sunflower husks and lucerne hay-based diets were rated as less offensive (mean
rank = 2.2) than maize cob diets (mean rank of 4.3) (p<0.05). CONCLUSION: It was
concluded that different fibre sources and incubation period influence chemical
composition and odour of the slurry. There is, thereby, a need to incorporate
locally available fibrous feeds in the diet of pigs because they have an
economical and environmental relevance to pig management.
PMID- 27608638
TI - Effects of ambient temperature and dietary glycerol addition on growth
performance, blood parameters and immune cell populations of Korean cattle
steers.
AB - OBJECTIVE: This study was performed to evaluate whether ambient temperature and
dietary glycerol addition affect growth performance, and blood metabolic and
immunological parameters, in beef cattle. METHODS: Twenty Korean cattle steers
(405.1+/-7.11 kg of body weight [BW], 14.2+/-0.15 months of age) were divided
into a conventional control diet group (n = 10) and a 2% glycerol- added group (n
= 10). Steers were fed 1.6% BW of a concentrate diet and 0.75% BW of a timothy
hay diet for 8 weeks (4 weeks from July 28th to August 26th and 4 weeks from
August 27th to September 26th). Blood was collected four times on July 28th,
August 11th, August 27th, and September 26th. RESULTS: The maximum indoor ambient
temperature-humidity index in August (75.8) was higher (p<0.001) than that in
September (70.0), and in August was within the mild heat stress (HS) category
range previously reported for dairy cattle. The average daily gain (ADG; p =
0.03) and feed efficiency (p<0.001) were higher in hotter August than in
September. Glycerol addition did not affect ADG and feed efficiency. Neither
month nor glycerol addition affected blood concentrations of cortisol,
triglyceride, or non-esterified fatty acid. Blood concentrations of cholesterol,
low-density lipoprotein, high-density lipoprotein, glucose, and albumin were
lower (p<0.05) on August 27th than on September 26 th, and blood phosphorus,
calcium and magnesium concentrations were also lower on August 27th than on
September 27th. Glycerol addition did not affect these blood parameters.
Percentages of CD4+ T cells and CD8+ T cells were higher (p<0.05) on July 28th
than on August 27th and September 26th. The blood CD8+ T cell population was
lower in the glycerol supplemented-group compared to the control group on July
28th and August 27th. CONCLUSION: Korean cattle may not be significantly affected
by mild HS, considering that growth performance of cattle was better in hotter
conditions, although some changes in blood metabolic and mineral parameters were
observed.
PMID- 27608639
TI - Farm to abattoir conditions, animal factors and their subsequent effects on
cattle behavioural responses and beef quality - A review.
AB - The current review seeks to highlight the concerns that have been raised on pre
slaughter stress, contributing factors and its consequent effects on cattle
behavioural responses and the quality of beef; inter-linking the activities
involved from birth to slaughter. Such information is crucial in light of the
consumer concerns on overall animal welfare, quality of meat and food security.
Slaughter animals are exposed to different conditions during production and
transportation to abattoirs on a daily basis. However; the majority of studies
that have been done previously singled out different environments in the meat
production chain, while conclusions have been made that the welfare of slaughter
animals and the quality of meat harvested from them is dependent on the whole
chain. Behaviour is a critical component used to evaluate the animals' wellbeing
and it has been reported to have an effect on product quality. Apart from the
influence of on-farm, transportation and abattoir conditions, the genetic
background of the animal also affects how it perceives and responds to certain
encounters. Stress activates the animals' hypothalamic-pituitary-adrenal
activity, triggering release of various stress hormones such as catecholamines
and cortisol, thus glycogen depletion prior slaughter, elevated ultimate pH and
poor muscle-meat conversion. Pre-slaughter stress sometimes results to cattle
attaining bruises, resulting to the affected parts of the carcass being trimmed
and condemned for human consumption, downgrading of the carcass and thus profit
losses.
PMID- 27608640
TI - Supplementation of L-Threonine for Optimization of Dietary Crude Protein Levels
in Broilers.
AB - This study was conducted to evaluate the performance of broiler chickens fed low
protein diets supplemented with L-threonine. Four hundred and sixty two 1-day-old
broiler chicks were randomly allotted to seven treatments with six replicates
each and eleven chicks per replicate. Seven treatments included; T1-control, T2,
T4, T6-without L-threonine and T3, T5 ,T7-with L-threonine supplementation with a
CP reduction by 0.75, 1.50 and 2.25 per cent units, respectively. Feed was
offered in pre-starter (0-14 days), starter (15-28 days) and finisher phases (29
42 days). On cumulative basis, body weight gain (BWG) was significantly (p<0.05)
reduced by step-down of dietary CP levels without L-threonine supplementation and
L-threonine supplementation significantly (p<0.05) improved BWG, but not the CP
reduction by 2.25 per cent unit. Feed intake was significantly (p<0.05) reduced
due to CP reduction at and above 1.5 per cent unit. Meanwhile, supplementation of
L-threonine improved feed intake on par to control. The FCR with L-threonine
supplementation improved only at 0.75 per cent CP reduction (T3) but not with
further CP reduction. The breast, thigh and drumstick absolute and relative
weights were significantly (p<0.05) decreased with CP reduction, at and beyond
1.50 per cent unit. L-Threonine addition improved the breast, thigh and drumstick
weights at CP reduction of 1.50 per cent units but not at CP reduction at 2.25
per cent units. Abdominal fat (AF) weight increased at and beyond 1.5 per cent
units CP reduction without L-threonine supplementation and with threonine, 1.5
per cent units CP reduced diet was similar to control. The relative AF weight was
increased with the CP reduction of 0.75 per cent without L-threonine
supplementation, while upon addition of L-threonine, AF per cent decreased as
that of control. These results conclude that, with L-threonine supplementation,
the CP can be reduced by 1.5 per cent units without affecting bird performance.
PMID- 27608641
TI - Performance and milk composition of dairy goats as affected by the dietary level
of stoned olive cake silages.
AB - OBJECTIVE: The current study compared the effects of dietary levels of two phase
stoned olive cake (OC) in form of silage (OCS) on milk production and quality of
Saanen goats. METHODS: The OCS included in total mixed ration (TMR) at dry matter
proportions of 0.0 (OC0), 0.10 (OC10), and 0.20 (OC20). The TMR were fed to a
total of 18 goats in a completely randomized design for a period of 5 weeks.
RESULTS: Dietary treatments had no effect on the milk yield of Saanen goats, but
the daily milk fat production was greater (p<0.05) at feeding OC20. The total
phenolic (TP) compounds contents increased (p<0.01) in each increment of OCS in
TMR and this was also reflected in the TP contents of milk. The C8:0, C10:0,
C12:0, and C14:0 saturated fatty acids (FAs) in milk fat decreased (p<0.01) with
increasing dietary level of OCS, but the decrease (p<0.001) in C16:0 and the
increase (p<0.01) in C18:0 in milk fat occurred similarly at each inclusion level
of OCS. Only OC20 reduced (p<0.05) the total saturated FA, yet the reduction
(p<0.01) in n6/n3 ratio and atherogenicity index occurred in both OC10 and OC20.
CONCLUSION: Two phase stoned OCS increases milk quality not only through
modifying the milk FA composition, but also by increasing the milk TP content.
These favorable changes in milk quality are closely associated with the dietary
level of OCS.
PMID- 27608642
TI - Different Coefficients and Exponents for Metabolic Body Weight in a Model to
Estimate Individual Feed Intake for Growing-finishing Pigs.
AB - Estimation of feed intake (FI) for individual animals within a pen is needed in
situations where more than one animal share a feeder during feeding trials. A
partitioning method (PM) was previously published as a model to estimate the
individual FI (IFI). Briefly, the IFI of a pig within the pen was calculated by
partitioning IFI into IFI for maintenance (IFIm) and IFI for growth. In the PM,
IFIm is determined based on the metabolic body weight (BW), which is calculated
using the coefficient of 106 and exponent of 0.75. Two simulation studies were
conducted to test the hypothesis that the use of different coefficients and
exponents for metabolic BW to calculate IFIm improves the accuracy of the
estimates of IFI for pigs, and that PM is applied to pigs fed in group-housing
systems. The accuracy of prediction represented by difference between actual and
estimated IFI was compared using PM, ratio (RM), or averaging method (AM). In
simulation studies 1 and 2, the PM estimated IFI better than the AM and RM during
most of the periods (p<0.05). The use of 0.60 as the exponent and the coefficient
of 197 to calculate metabolic BW did not improve the accuracy of the IFI
estimates in both simulation studies 1 and 2. The results imply that the use of
197 kcal*kg BW0.60 as metabolizable energy for maintenance in PM does not improve
the accuracy of IFI estimations compared with the use of 106 kcal*kg BW0.75 and
that the PM estimates the IFI of pigs with greater accuracy compared with the
averaging or ratio methods in group-housing systems.
PMID- 27608643
TI - Genetic Parameters of Milk beta-Hydroxybutyric Acid and Acetone and Their Genetic
Association with Milk Production Traits of Holstein Cattle.
AB - This study was conducted to estimate the genetic parameters of beta
hydroxybutyrate (BHBA) and acetone concentration in milk by Fourier transform
infrared spectroscopy along with test-day milk production traits including fat %,
protein % and milk yield based on monthly samples of milk obtained as part of a
routine milk recording program in Korea. Additionally, the feasibility of using
such data in the official dairy cattle breeding system for selection of cows with
low susceptibility of ketosis was evaluated. A total of 57,190 monthly test-day
records for parities 1, 2, and 3 of 7,895 cows with pedigree information were
collected from April 2012 to August 2014 from herds enrolled in the Korea Animal
Improvement Association. Multi-trait random regression models were separately
applied to estimate genetic parameters of test-day records for each parity. The
model included fixed herd test-day effects, calving age and season effects, and
random regressions for additive genetic and permanent environmental effects.
Abundance of variation of acetone may provide a more sensitive indication of
ketosis than many zero observations in concentration of milk BHBA. Heritabilities
of milk BHBA levels ranged from 0.04 to 0.17 with a mean of 0.09 for the interval
between 4 and 305 days in milk during three lactations. The average
heritabilities for milk acetone concentration were 0.29, 0.29, and 0.22 for
parities 1, 2, and 3, respectively. There was no clear genetic association of the
concentration of two ketone bodies with three test-day milk production traits,
even if some correlations among breeding values of the test-day records in this
study were observed. These results suggest that genetic selection for low
susceptibility of ketosis in early lactation is possible. Further, it is
desirable for the breeding scheme of dairy cattle to include the records of milk
acetone rather than the records of milk BHBA.
PMID- 27608644
TI - Low IgE Is a Useful Tool to Identify STAT3 Gain-of-Function Mutations.
PMID- 27608645
TI - Reach and Implementation of Physical Activity Breaks and Active Lessons in
Elementary School Classrooms.
AB - The integration of physical activity into elementary school classrooms, through
brief activity breaks (ABs) and lessons that incorporate movement into
instruction as active lessons (ALs), are key parts of school physical activity
programming and can improve children's health and academic outcomes. With
nationally representative survey data from 640 public elementary schools in the
United States, we examined the use of these practices and the extent of
implementation within classrooms. ALs were used in 71.7% of schools, and ABs were
used in 75.6% of schools. In multivariate models, ALs were significantly less
likely to be used in majority-Latino schools (adjusted odds ratio = 0.48, 95%
confidence interval [0.25, 0.93], p < .05) than in predominantly White schools.
ABs were significantly less likely to be used in lower socioeconomic schools
(adjusted odds ratio = 0.57, 95% confidence interval [0.34, 0.95], p < .05) than
in higher socioeconomic schools. At schools where ABs were ever used, they were
used by 45.6% of teachers, but fewer teachers used them at larger schools (beta =
-.08, p < .01) and at lower socioeconomic schools (beta = -.09, p < .05). The
reach of ALs and ABs is modest and classroom-level implementation is quite low.
Additional dissemination and support is warranted to improve the reach and
implementation of these strategies in elementary schools. Such efforts could
improve the school-day experience in ways that benefit millions of young
children.
PMID- 27608647
TI - Swedish government sacks entire Karolinska Institute board over Macchiarini.
PMID- 27608646
TI - Safety and pharmacokinetics of ramucirumab in combination with docetaxel in
Japanese patients with locally advanced or metastatic breast cancer: a Phase Ib
study.
AB - OBJECTIVE: The primary objective of this study was to investigate the safety and
tolerability and to confirm the recommended dose of the anti-vascular endothelial
growth factor receptor 2 monoclonal antibody ramucirumab in combination with
docetaxel in Japanese patients with metastatic/locally advanced breast cancer.
METHODS: In this multicenter, single-arm, Phase Ib trial, eligibility criteria
included: 20 years or older, Eastern Cooperative Oncology Group performance
status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2
negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients
received docetaxel (75 mg/m2) followed by ramucirumab (10 mg/kg) on Day 1 of 21
day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose
limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics,
immunogenicity and antitumor activity were examined. RESULTS: Seven patients were
treated. Most adverse events were mild to moderate. Two patients during Cycle 1
experienced a dose-limiting toxicity; one patient each experienced Grade 3
febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities
subsequently resolved. No patients discontinued study therapies during Cycle 1.
Four serious adverse events were possibly related to ramucirumab in combination
with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic
analysis revealed low total body clearance and long apparent terminal elimination
half-life (~7-12 days). Partial response was reported in four patients.
CONCLUSIONS: The combination of ramucirumab and docetaxel was tolerable in female
Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with
docetaxel (75 mg/m2) was confirmed as the recommended dose among Japanese
patients, supporting its use in future studies.
PMID- 27608649
TI - When Payment Undermines the Pitch.
AB - Studies on crowding out document that incentives sometimes backfire-decreasing
motivation in prosocial tasks. In the present research, we demonstrated an
additional channel through which incentives can be harmful. Incentivized
advocates for a cause are perceived as less sincere than nonincentivized
advocates and are ultimately less effective in persuading other people to donate.
Further, the negative effects of incentives hold only when the incentives imply a
selfish motive; advocates who are offered a matching incentive (i.e., who are
told that the donations they successfully solicit will be matched), which is not
incompatible with altruism, perform just as well as those who are not
incentivized. Thus, incentives may affect prosocial outcomes in ways not
previously investigated: by crowding out individuals' sincerity of expression and
thus their ability to gain support for a cause.
PMID- 27608648
TI - Differentiation of Chronic and Aggressive Periodontitis by FTIR Spectroscopy.
AB - Without longitudinal clinical data, it is difficult to differentiate some cases
of chronic periodontitis (CP) and aggressive periodontitis (AgP). Furthermore,
both forms of disease are exacerbated by tobacco use. Therefore, this cross
sectional study was planned, primarily, to determine the ability of Fourier
transform infrared (FTIR) spectroscopy to distinguish CP and AgP patients by
analysis of human saliva samples and, secondarily, to assess the potential
confounding influence of smoking on discriminating disease-specific spectral
signatures. FTIR spectra were collected from patients with a clinical diagnosis
of CP (n = 18; 7 smokers) or AgP (n = 23; 9 smokers). Self-reported smoking
status, which may be unreliable, was confirmed by salivary cotinine analysis.
Spectral band area analysis and hierarchical cluster analyses were performed to
clarify if the 2 periodontitis groups as well as smoker and nonsmoker patients
could be differentiated from each other. Significant variations in lipid, amino
acid, lactic acid, and nucleic acid content were found between nonsmoker CP and
AgP groups. Although significantly lower lipid, phospholipid, protein, amino
acid, lactic acid, and nucleic acid content was noted in the smoker AgP group
compared with the nonsmoker AgP group, in the CP group, phospholipid, protein,
amino acid, and lactic acid content was significantly lower for smokers compared
with the nonsmokers. Based on these variations, nonsmoker CP and AgP patients
were discriminated from each other with high sensitivity and specificity.
Successful differentiation was also obtained for the smoker CP and AgP groups.
Thiocyanate levels successfully differentiated smokers from nonsmokers,
irrespective of periodontal status, with 100% accuracy. Differentiation of AgP
and CP forms, concomitant with determination of smoking status, may allow the
dental health professional to tailor treatment accordingly.
PMID- 27608651
TI - Serial weighting of micro-objects with resonant microchanneled cantilevers.
AB - Atomic force microscopy (AFM) cantilevers have proven to be very effective mass
sensors. The attachment of a small mass to a vibrating cantilever produces a
resonance frequency shift that can be monitored, providing the ability to measure
mass changes down to a few molecules resolution. Nevertheless, the lack of a
practical method to handle the catch and release process required for dynamic
weighting of microobjects strongly hindered the application of the technology
beyond proof of concept measurements. Here, a method is proposed in which FluidFM
hollow cantilevers are exploited to overcome the standard limitations of AFM
based mass sensors, providing high throughput single object weighting with
picogram accuracy. The extension of the dynamic models of AFM cantilevers to
hollow cantilevers was discussed and the effectiveness of mass weighting in air
was validated on test samples.
PMID- 27608650
TI - The histological and elemental characterisation of corrosion particles from taper
junctions.
AB - OBJECTIVES: This study aimed to characterise and qualitatively grade the severity
of the corrosion particles released into the hip joint following taper corrosion.
METHODS: The 26 cases examined were CoC/ABG Modular (n = 13) and ASR/SROM (n =
13). Blood serum metal ion levels were collected before and after revision
surgery. The haematoxylin and eosin tissue sections were graded on the presence
of fibrin exudates, necrosis, inflammatory cells and corrosion products. The
corrosion products were identified based on visible observation and graded on
abundance. Two independent observers blinded to the clinical patient findings
scored all cases. Elemental analysis was performed on corrosion products within
tissue sections. X-Ray diffraction was used to identify crystalline structures
present in taper debris. RESULTS: The CoC/ABG Modular patients had a mean age of
64.6 years (49.4 to 76.5) and ASR/SROM patients had a mean age of 58.2 years
(33.3 to 85.6). The mean time in situ for CoC/ABG was 4.9 years (2 to 6.4) and
ASR/SROM was 6.1 years (2.5 to 8.1). The blood serum metal ion concentrations
reduced following revision surgery with the exception of Cr levels within
CoC/ABG. The grading of tissue sections showed that the macrophage response and
metal debris were significantly higher for the ASR/SROM patients (p < 0.001). The
brown/red particles were significantly higher for ASR/SROM (p < 0.001). The taper
debris contained traces of titanium oxide, chromium oxide and aluminium nitride.
CONCLUSION: This study characterised and qualitatively graded the severity of the
corrosion particles released into the hip joint from tapers that had corrosion
damage.Cite this article: S. Munir, R. A. Oliver, B. Zicat, W. L. Walter, W. K.
Walter, W. R. Walsh. The histological and elemental characterisation of corrosion
particles from taper junctions. Bone Joint Res 2016;5:370-378. DOI: 10.1302/2046
3758.59.2000507.
PMID- 27608652
TI - Human motor adaptation in whole body motion.
AB - The main role of the sensorimotor system of an organism is to increase the
survival of the species. Therefore, to understand the adaptation and optimality
mechanisms of motor control, it is necessary to study the sensorimotor system in
terms of ecological fitness. We designed an experimental paradigm that exposed
sensorimotor system to risk of injury. We studied human subjects performing uncon
strained squat-to-stand movements that were systematically subjected to non
trivial perturbation. We found that subjects adapted by actively compensating the
perturbations, converging to movements that were different from their normal
unperturbed squat-to-stand movements. Furthermore, the adapted movements had
clear intrinsic inter-subject differences which could be explained by different
adapta- tion strategies employed by the subjects. These results suggest that
classical optimality measures of physical energy and task satisfaction should be
seen as part of a hierarchical organization of optimality with safety being at
the highest level. Therefore, in addition to physical energy and task
fulfillment, the risk of injury and other possible costs such as neural
computational overhead have to be considered when analyzing human movement.
PMID- 27608653
TI - Aspect ratio effects on revolving wings with Rossby number consideration.
AB - Numerical simulations have been conducted to investigate the effect of aspect
ratio (AR) on the mean lift generation of a revolving flat rectangular wing. The
purpose of the study is to address some discrepancies reported in the literature
regarding the influence of AR on mean lift coefficient. Here, we consider a range
of AR from 1 to 10 and Rossby number (Ro) from 0.58 to 7.57, and our results show
that different degrees of coupling between AR and Ro yield different trends of a
mean lift coefficient with respect to increasing AR. The choice of reference
velocity for the normalisation of mean lift forces also has a significant effect
on the perceived AR effect. By isolating the effect of Ro, we found that higher
AR produces higher mean lift coefficient until it plateaus at a sufficiently high
AR. This finding is consistent with conventional fixed wing aerodynamics.
Additionally, our results show that increasing AR reduces the three-dimensional
wing tip effect and is beneficial to mean lift generation while higher Ro
increases leading-edge vortex instability, which is detrimental to mean lift
generation. Therefore, mean lift generation on revolving wings is dictated by the
competition between these two factors, which represent two fundamentally
independent phenomena.
PMID- 27608654
TI - Remediation for Students With Mathematics Difficulties: An Intervention Study in
Middle Schools.
AB - As empirical studies have consistently shown, low achievement in mathematics at
the secondary level can often be traced to deficits in the understanding of
certain basic arithmetic concepts taught in primary school. The present
intervention study in middle schools evaluated whether such learning deficits can
be reduced effectively and whether the type of instruction influences students'
progress. The sample consisted of 123 students in 34 classes, split among one
control group and two intervention groups: (a) small group instruction and (b)
independent work partially integrated into regular classrooms. Over a period of
14 weeks, students were taught basic concepts, such as place value and basic
operations. In addition, they practiced fact retrieval and counting (in groups).
Multilevel regression analyses demonstrated that the interventions can be used to
reduce given deficits.
PMID- 27608655
TI - Working Memory Load and Reminder Effect on Event-Based Prospective Memory of High
and Low-Achieving Students in Math.
AB - The effects of working memory (WM) demand and reminders on an event-based
prospective memory (PM) task were compared between students with low and high
achievement in math. WM load (1- and 2-back tasks) was manipulated as a within
subject factor and reminder (with or without reminder) as a between-subject
factor. Results showed that high-achieving students outperformed low-achieving
students on all PM and n-back tasks. Use of a reminder improved PM performance
and thus reduced prospective interference; the performance of ongoing tasks also
improved for all students. Both PM and n-back performances in low WM load were
better than in high WM load. High WM load had more influence on low-achieving
students than on high-achieving students. Results suggest that low-achieving
students in math were weak at PM and influenced more by high WM load. Thus, it is
important to train these students to set up an obvious reminder for their PM and
improve their WM.
PMID- 27608656
TI - Identification and Characterization of New Chemical Entities Targeting
Apurinic/Apyrimidinic Endonuclease 1 for the Prevention of Chemotherapy-Induced
Peripheral Neuropathy.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating
side effect of a number of chemotherapeutic agents. There are currently no U.S.
Food and Drug Administration-approved interventions or prevention strategies for
CIPN. Although the cellular mechanisms mediating CIPN remain to be determined,
several lines of evidence support the notion that DNA damage caused by anticancer
therapies could contribute to the neuropathy. DNA damage in sensory neurons after
chemotherapy correlates with symptoms of CIPN. Augmenting apurinic/apyrimidinic
endonuclease (APE)-1 function in the base excision repair pathway reverses this
damage and the neurotoxicity caused by anticancer therapies. This neuronal
protection is accomplished by either overexpressing APE1 or by using a first
generation targeted APE1 small molecule, E3330 [(2E)-2-[(4,5-dimethoxy-2-methyl
3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid; also called
APX3330]. Although E3330 has been approved for phase 1 clinical trials
(Investigational New Drug application number IND125360), we synthesized novel,
second-generation APE1-targeted molecules and determined whether they would be
protective against neurotoxicity induced by cisplatin or oxaliplatin while not
diminishing the platins' antitumor effect. We measured various endpoints of
neurotoxicity using our ex vivo model of sensory neurons in culture, and we
determined that APX2009 [(2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2
yl)methylidene]-N,N-diethylpentanamide] is an effective small molecule that is
neuroprotective against cisplatin and oxaliplatin-induced toxicity. APX2009 also
demonstrated a strong tumor cell killing effect in tumor cells and the enhanced
tumor cell killing was further substantiated in a more robust three-dimensional
pancreatic tumor model. Together, these data suggest that the second-generation
compound APX2009 is effective in preventing or reversing platinum-induced CIPN
while not affecting the anticancer activity of platins.
PMID- 27608657
TI - Palmitoylethanolamide Reverses Paclitaxel-Induced Allodynia in Mice.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) represents a serious
complication associated with antineoplastic drugs. Although there are no
medications available that effectively prevent CIPN, many classes of drugs have
been used to treat this condition, including anticonvulsants, serotonin and
noradrenaline reuptake inhibitors, and opioids. However, these therapeutic
options yielded inconclusive results in CIPN clinical trials and produced
assorted side effects with their prolonged use. Thus, there is an urgent need to
develop efficacious and safe treatments for CIPN. In this report, we tested
whether the endogenous lipid palmitoylethanolamide (PEA) alone or in combination
with the anticonvulsant gabapentin would reduce allodynia in a mouse paclitaxel
model of CIPN. Gabapentin and PEA reversed paclitaxel-induced allodynia with
respective ED50 doses (95% confidence interval) of 67.4 (61.52-73.94) and 9.2
(8.39-10.16) mg/kg. Isobolographic analysis of these drugs in combination
revealed synergistic antiallodynic effects. The PPAR-alpha antagonist receptor
antagonist GW6471 [N-((2S)-2-(((1Z)-1-methyl-3-oxo-3-(4
(trifluoromethyl)phenyl)prop-1-enyl)amino)-3-(4-(2-(5-methyl-2-phenyl-1,3-oxazol
4-yl)ethoxy)phenyl)propyl)propanamide] completely blocked the antinociceptive
effects of PEA. In addition, PEA administered via intraplantar injection into a
paw, intrathecal injection, and intracerebroventricular injection reversed
paclitaxel-induced allodynia, suggesting that it may act at multiple sites in the
neuroaxis and periphery. Finally, repeated administration of PEA (30 mg/kg, 7
days) preserved the antiallodynic effects with no evidence of tolerance. These
findings taken together suggest that PEA possesses potential to treat peripheral
neuropathy in cancer patients undergoing chemotherapy.
PMID- 27608659
TI - Evaluation of enzymatically treated Artemisia annua L. on growth performance,
meat quality, and oxidative stability of breast and thigh muscles in broilers.
AB - An experiment was conducted to evaluate the effects of including enzymatically
treated Artemisia annua L. (EA) in broiler diets on growth performance, meat
quality, and oxidative stability of breast and thigh muscles. A total of 256 one
d-old Arbor Acres broiler chicks were randomly allotted into four groups with
eight replicates of eight birds each. Broilers in the four groups were offered
basal diet supplemented with 0.0, 0.5, 1.0, and 1.5 g/kg EA during the 42-d
experiment, respectively. The ADG, ADFI, and feed/gain ratio (F:G) were measured
at 42 d of age. Breast and thigh muscle samples from eight birds per treatment
were obtained at 42 d to determine meat quality, free radical scavenging
activity, and lipid peroxidation. All treatment groups had similar ADG, ADFI, and
F:G during the 42 d experiment (P > 0.05). Drip loss at 24 h and shearing force
of breast muscle were linearly (P < 0.05) and quadratically (P < 0.05) decreased
by EA addition. The drip loss at 24 h and 48 h, cooking loss and shearing force
of thigh muscle followed the same fashion. The supplementation of EA
quadratically increased 2, 2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)
diammonium salt (ABTS) (P = 0.004) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (P =
0.035) free radical scavenging activities in breast muscle, and linearly (P <
0.05) and quadratically (P < 0.05) increased ABTS and DPPH scavenging activities
of thigh muscle. Increasing levels of EA linearly (P < 0.05) or quadratically (P
< 0.05) or both decreased the malondialdehyde (MDA) concentrations in breast and
thigh muscle samples during 15 d of storage at 4 degrees C. The results indicated
that EA supplementation improved meat quality and oxidative stability of breast
and thigh muscles in broilers. The inclusion level of 1.0 g/kg EA in broiler diet
was recommended.
PMID- 27608658
TI - Complete Defluorination of Perfluorinated Compounds by Hydrated Electrons
Generated from 3-Indole-acetic-acid in Organomodified Montmorillonite.
AB - Here we describe a unique process that achieves complete defluorination and
decomposition of perfluorinated compounds (PFCs) which comprise one of the most
recalcitrant and widely distributed classes of toxic pollutant chemicals found in
natural environments. Photogenerated hydrated electrons derived from 3-indole
acetic-acid within an organomodified clay induce the reductive defluorination of
co-sorbed PFCs. The process proceeds to completion within a few hours under mild
reaction conditions. The organomontmorillonite clay promotes the formation of
highly reactive hydrated electrons by stabilizing indole radical cations formed
upon photolysis, and prevents their deactivation by reaction with protons or
oxygen. In the constrained interlayer regions of the clay, hydrated electrons and
co-sorbed PFCs are brought in close proximity thereby increasing the probability
of reaction. This novel green chemistry provides the basis for in situ and ex
situ technologies to treat one of the most troublesome, recalcitrant and
ubiquitous classes of environmental contaminants, i.e., PFCs, utilizing innocuous
reagents, naturally occurring materials and mild reaction conditions.
PMID- 27608660
TI - Comparison of the meat metabolite composition of Linwu and Pekin ducks using 600
MHz 1H nuclear magnetic resonance spectroscopy.
AB - In an effort to further understand of the differences of meat flavor and texture
between Linwu ducks and Pekin ducks at market age, we investigated the meat
metabolite composition of the two breeds of ducks using 600 MHz 1H nuclear
magnetic resonance (NMR) spectroscopy. Comprehensive multivariate data analysis
including principal component analysis (PCA), partial least squares discriminant
analysis (PLS-DA), and orthogonal projection to latent structure-discriminant
analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify
the distinguishing metabolites of breast meat between two breeds of ducks.
Compared with 42-d-old Pekin duck meat, breast from 72-d-old Linwu duck has
higher concentration of anserine, carnosine, homocarnosine, and nicotinamide, but
significantly lower concentration of succinate, creatine, and myo-inositol. These
results contribute to a better understanding of the differences in meat
metabolite composition between 72-d-old Linwu and 42-d-old Pekin ducks, which
could be used to help assess the quality of duck meat as a food.
PMID- 27608661
TI - Moving at the frontline.
AB - The factors that regulate how immune cells called innate-like lymphocytes are
localized in the tissue have been identified.
PMID- 27608662
TI - Risks of Death and Severe Disease in Patients With Middle East Respiratory
Syndrome Coronavirus, 2012-2015.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen,
first recognized in 2012, with a high case fatality risk, no vaccine, and no
treatment beyond supportive care. We estimated the relative risks of death and
severe disease among MERS-CoV patients in the Middle East between 2012 and 2015
for several risk factors, using Poisson regression with robust variance and a
bootstrap-based expectation maximization algorithm to handle extensive missing
data. Increased age and underlying comorbidity were risk factors for both death
and severe disease, while cases arising in Saudi Arabia were more likely to be
severe. Cases occurring later in the emergence of MERS-CoV and among health-care
workers were less serious. This study represents an attempt to estimate risk
factors for an emerging infectious disease using open data and to address some of
the uncertainty surrounding MERS-CoV epidemiology.
PMID- 27608663
TI - Evaluation of a Computer-Based Recruitment System for Enrolling Men Who Have Sex
With Men Into an Observational HIV Behavioral Risk Study.
AB - Enrolling large numbers of high-risk men who have sex with men (MSM) into human
immunodeficiency virus (HIV) prevention studies is necessary for research with an
HIV outcome, but the resources required for in-person recruitment can be
prohibitive. New methods with which to efficiently recruit large samples of MSM
are needed. At a sexually transmitted disease clinic in Seattle, Washington, in
2013-2014, we used an existing clinical computer-assisted self-interview that
collects patients' medical and sexual history data to recruit, screen, and enroll
MSM into an HIV behavioral risk study and compared enrollees with men who
declined to enroll. After completing the clinical computer-assisted self
interview, men aged >=18 years who reported having had sex with men in the prior
year were presented with an electronic study description and consent statement.
We enrolled men at 2,661 (54%) of 4,944 visits, including 1,748 unique
individuals. Enrolled men were younger (mean age = 34 years vs. 37 years; P <
0.001) and reported more male sex partners (11 vs. 8; P < 0.001) and more
methamphetamine use (15% vs. 8%; P < 0.001) than men who declined to enroll, but
the HIV test positivity of the two groups was similar (1.9% vs. 2.0%; P = 0.80).
Adapting an existing computerized clinic intake system, we recruited a large
sample of MSM who may be an ideal population for an HIV prevention study.
PMID- 27608664
TI - Increased Incidence Rate of Trauma- and Stressor-Related Disorders in Denmark
After the September 11, 2001, Terrorist Attacks in the United States.
AB - The terrorist attacks that occurred on September 11, 2001 (hereafter referred to
as 9/11) in the United States had a profound impact on the physical and mental
health of Americans, but the effects beyond the United States are largely
unknown. To understand the wider aftermath, we examined the consequences of the
9/11 attacks on mental disorders in the Kingdom of Denmark. Utilizing population
data from the Danish Psychiatric Central Research Register from 1995 to 2012, we
used a time-series intervention approach to estimate the change in the incidence
rate of mental disorders after the 9/11 attacks. Based on analyses of 1,448,250
contacts with psychiatric services, we found that the attacks were followed by an
immediate 16% increase in the incidence rate of trauma- and stressor-related
disorders. This surge dissipated approximately a year after 9/11. In contrast, no
similar increases were found for other disorders. This is consistent with the
prominent role of external stressors in the etiology of trauma- and stressor
related disorders. The results indicate that the effects of 9/11 on mental
disorders extended across the Atlantic Ocean to Denmark. Thus, the impact of
terrorist attacks on mental health is likely not limited to inhabitants of the
country under attack; it also extends to people far away and without immediate
relation to it.
PMID- 27608665
TI - Probing conformational and functional states of human hepatocyte growth factor by
a panel of monoclonal antibodies.
AB - HGF-Met signaling contributes to various biological events by controlling cell
migration. Since the abnormal activation of Met receptor causes cancer
progression, inhibitors such as neutralizing antibodies are regarded as promising
therapeutics. HGF is secreted as a single-chain (sc) precursor and is processed
by extracellular proteases to generate disulfide-bonded two-chain (tc) HGF.
Although this proteolytic processing of HGF is necessary for its biological
activity, exactly how the proteolysis leads to the conversion of HGF to the
active form is still unclar due to the lack of structural information. In order
to gain insights about this point, we generated 6 antibodies against HGF. All
antibodies recognized different epitopes on the native HGF protein and showed
distinct effects when tested in a cell-based HGF-Met signaling assay. They
included one antibody (t1E4) that strongly blocks Met activation by tcHGF, as
well as one antibody (t8E4) exclusively recognizing the active tcHGF but not
inactive scHGF. Thus, a panel of anti-HGF antibodies suitable for probing the
structural mechanism of HGF activation were obtained.
PMID- 27608666
TI - An unexpected disruption of the atmospheric quasi-biennial oscillation.
AB - One of the most repeatable phenomena seen in the atmosphere, the quasi-biennial
oscillation (QBO) between prevailing eastward and westward wind jets in the
equatorial stratosphere (approximately 16 to 50 kilometers altitude), was
unexpectedly disrupted in February 2016. An unprecedented westward jet formed
within the eastward phase in the lower stratosphere and cannot be accounted for
by the standard QBO paradigm based on vertical momentum transport. Instead, the
primary cause was waves transporting momentum from the Northern Hemisphere.
Seasonal forecasts did not predict the disruption, but analogous QBO disruptions
are seen very occasionally in some climate simulations. A return to more typical
QBO behavior within the next year is forecast, although the possibility of more
frequent occurrences of similar disruptions is projected for a warming climate.
PMID- 27608667
TI - A "Trojan horse" bispecific-antibody strategy for broad protection against
ebolaviruses.
AB - There is an urgent need for monoclonal antibody (mAb) therapies that broadly
protect against Ebola virus and other filoviruses. The conserved, essential
interaction between the filovirus glycoprotein, GP, and its entry receptor
Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is
shielded by multiple mechanisms, including physical sequestration in late
endosomes. Here, we describe a bispecific-antibody strategy to target this
interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are
coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific
antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting
viral particles themselves for endosomal delivery and conferred postexposure
protection against multiple ebolaviruses in mice. Such "Trojan horse" bispecific
antibodies have potential as broad antifilovirus immunotherapeutics.
PMID- 27608669
TI - Deterministic generation of a cluster state of entangled photons.
AB - Photonic cluster states are a resource for quantum computation based solely on
single-photon measurements. We use semiconductor quantum dots to
deterministically generate long strings of polarization-entangled photons in a
cluster state by periodic timed excitation of a precessing matter qubit. In each
period, an entangled photon is added to the cluster state formed by the matter
qubit and the previously emitted photons. In our prototype device, the qubit is
the confined dark exciton, and it produces strings of hundreds of photons in
which the entanglement persists over five sequential photons. The measured
process map characterizing the device has a fidelity of 0.81 with that of an
ideal device. Further feasible improvements of this device may reduce the
resources needed for optical quantum information processing.
PMID- 27608670
TI - The contribution of family medicine to African health systems.
AB - No abstract available.
PMID- 27608668
TI - Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci
transgenic mice.
AB - A major obstacle to a broadly neutralizing antibody (bnAb)-based HIV vaccine is
the activation of appropriate B cell precursors. Germline-targeting immunogens
must be capable of priming rare bnAb precursors in the physiological setting. We
tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8
60mer (60-subunit self-assembling nanoparticle) to activate appropriate
precursors in mice transgenic for human immunoglobulin (Ig) loci. Despite an
average frequency of, at most, about one VRC01-class precursor per mouse, we
found that at least 29% of singly immunized mice produced a VRC01-class memory
response, suggesting that priming generally succeeded when at least one precursor
was present. The results demonstrate the feasibility of using germline targeting
to prime specific and exceedingly rare bnAb-precursor B cells within a humanlike
repertoire.
PMID- 27608671
TI - How to change organisational culture: Action research in a South African public
sector primary care facility.
AB - BACKGROUND: Organisational culture is a key factor in both patient and staff
experience of the healthcare services. Patient satisfaction, staff engagement and
performance are related to this experience. The department of health in the
Western Cape espouses a values-based culture characterised by caring, competence,
accountability, integrity, responsiveness and respect. However, transformation of
the existing culture is required to achieve this vision. AIM: To explore how to
transform the organisational culture in line with the desired values. SETTING:
Retreat Community Health Centre, Cape Town, South Africa. METHODS: Participatory
action research with the leadership engaged with action and reflection over a
period of 18 months. Change in the organisational culture was measured at
baseline and after 18 months by means of a cultural values assessment (CVA)
survey. The three key leaders at the health centre also completed a 360-degree
leadership values assessment (LVA) and had 6 months of coaching. RESULTS:
Cultural entropy was reduced from 33 to 13% indicating significant transformation
of organisational culture. The key driver of this transformation was change in
the leadership style and functioning. Retreat health centre shifted from a
culture that emphasised hierarchy, authority, command and control to one that
established a greater sense of cohesion, shared vision, open communication,
appreciation, respect, fairness and accountability. CONCLUSION: Transformation of
organisational culture was possible through a participatory process that focused
on the leadership style, communication and building relationships by means of CVA
and feedback, 360-degree LVA, feedback and coaching and action learning in a co
operative inquiry group.
PMID- 27608672
TI - Exploring the occupational therapist's role in primary health care: Listening to
voices of stakeholders.
AB - BACKGROUND: Re-engineering of primary healthcare (PHC) was initiated nationally
in 2009. There is, however, little information on the role expected of
occupational therapists (OTs)in PHC. OBJECTIVES: This research aimed to
understand how stakeholders of the Department of Health (DOH) perceived the role
of OT in PHC service. METHOD: This exploratory, qualitative study used purposive
sampling to recruit community health-care workers (CHW; n = 23), primary
healthcare nurses (PHC; n = 5), DOH management (n = 5), experienced (n = 14) and
novice OTs (n = 37) who graduated from the University of KwaZulu-Natal. The PHC
nurses and the CHW represented PHC clinics in one district in KwaZulu-Natal. Data
were collected through semi-structured interviews and focus groups. Interviews
with CHWs were conducted in isiZulu. These were transcribed and translated prior
to data analysis. Audio recordings of English interviews and focus groups were
transcribed. Data for each participant group were inductively and thematically
analysed to identify the themes. RESULTS: The findings provided an indication of
the role of OTs in PHC settings. All participants perceived the role of OTs as
predominantly curative/rehabilitation-based and individualised. Participants had
a limited understanding of the key principles of PHC. They identified a need for
adult and paediatric rehabilitation and early childhood intervention. Limited
mention was made of population-based approaches, collaborative, and health
promotion and prevention programmes. CONCLUSION: The study has highlighted that
neither management nor OTs seemed to align practice and planning according to PHC
principles. A review of the theory and experiential learning in the OT programme
is required.
PMID- 27608673
TI - Improving diabetic foot screening at a primary care clinic: A quality improvement
project.
AB - BACKGROUND: Foot screening is an important part of diabetic care as it prevents
significant morbidity, loss of function and mortality from diabetic foot
complications. However, foot screening is often neglected. AIM: This project was
aimed at educating health care workers (HCWs) in a primary health care clinic to
increase diabetic foot screening practices. SETTING: A primary health care clinic
in the Western Cape province of South AfricaMethods: A quality improvement
project was conducted. HCWs' needs were assessed using a questionnaire. This was
followed by focus group discussions with the HCWs, which were recorded,
transcribed and assessed using a general inductive approach. An intervention was
designed based on common themes. Staff members were trained on foot screening and
patient information pamphlets and screening tools were made available to all
clinic staff. Thirty-two consecutive diabetic patient folders were audited to
compare screening in 2013 with that in 2014 after initiation of the quality
improvement cycle. RESULTS: HCWs' confidence in conducting foot screening using
the diabetic foot assessment questionnaire improved markedly after training.
Diabetic foot screening practices increased from 9% in 2013 to 69% in 2014 after
the first quality improvement cycle. A strengths, opportunities, aspirations and
results (SOAR) analysis showed promise for continuing quality improvement cycles.
CONCLUSION: The findings showed a significant improvement in the number of
diabetic patients screened. Using strategic planning with appreciative intent
based on SOAR, proved to be motivational and can be used in the planning of the
next cycle.
PMID- 27608674
TI - Clients' perceptions and satisfaction with HIV counselling and testing: A cross
sectional study in 56 HCT sites in South Africa.
AB - BACKGROUND: Client satisfaction serves as a predictor for acceptance of HIV
counselling and testing (HCT) services. Therefore, the study of clients'
perception and satisfaction may offer insights on how to improve HCT programmes.
AIM AND SETTING: The aim of this study was to assess clients' satisfaction with
HCT as well as describe perceived barriers to and facilitators of HIV testing by
HCT clients in South Africa. METHODS: A cross-sectional survey was conducted
through interviews with 498 clients purposefully selected at the end of an HCT
visit at 56 HCT sites throughout the country. RESULTS: All the 498 study
participants had tested for HIV with 98.8% receiving their results. Most (88.2%)
reported testing for HIV before. The vast majority (75.5%) of clients reported
that they had decided to be tested for HIV by themselves. High levels of
satisfaction with HCT service (89.8%), low levels (27.7%) of difficulty in making
the decision to have an HIV test and high levels of perceived confidentiality
(94.6%) of the HIV test results were reported in this study. The most cited
perceived barrier to HIV testing was lack of awareness about the HCT service
(98%), while staff attitudes (37%), confidentiality (29.6%) and privacy (23.6%)
were perceived facilitators. In multivariate logistic regression, staff attitude
was significantly associated with client satisfaction (p < 0.05). CONCLUSION:
High levels of client satisfaction with HCT services were observed. Various
barriers to and facilitators of - including staff attitude - HCT were identified
which can help guide the improvement of HCT services in South Africa.
PMID- 27608675
TI - Relationship between HIV stage and psychomotor speed neurocognitive score at a
Kenyan sub-county hospital.
AB - BACKGROUND: Human immunodeficiency virus (HIV) and acquired immunodeficiency
syndrome (AIDS) is associated with cognitive impairment which affects psychomotor
speed. Psychomotor slowing is a predictor of dementia and death in people living
with HIV and AIDS. The purpose of this study was to assess the relationship
between HIV disease stage and psychomotor speed neurocognitive score which will
add to the body of knowledge required to manage patients with HIV and AIDS.
OBJECTIVE: To determine the relationship between psychomotor speed neurocognitive
score and the HIV disease stage in adults at initiation of care. SETTING: This
study was conducted at Kangundo Sub-county hospital comprehensive care centre.
METHODS: This was a cross-sectional study. All HIV seropositive patients aged 18
to 50 years recently initiated into care were studied. A pretested questionnaire
was used to collect data. The World Health Organization (WHO) stage was used
during data collection to classify study participants into asymptomatic and
symptomatic groups. The grooved pegboard test was used to obtain psychomotor
speed neurocognitive scores. Descriptive statistics were used to summarise data.
Mann-Whitney U test, Spearman's rho and multiple linear regression were employed
in the analysis; p-value of 0.05 was considered significant. RESULTS: The WHO
stage did not have a significant effect on the psychomotor speed neurocognitive
score (p >= 0.05). The CD4 count had a significant effect on psychomotor speed
neurocognitive score (p = 0.001). CONCLUSIONS: There was a significant
correlation between CD4 counts and psychomotor speed neurocognitive score.
Efforts should be made to ensure that the CD4 counts of people living with HIV
and AIDS do not continue to fall after initiation into care in order to preserve
psychomotor function.
PMID- 27608676
TI - Contraceptive practices among women seeking termination of pregnancy in one
public hospital in Eastern Cape, South Africa.
AB - BACKGROUND: There is significantly high contraceptive knowledge in South Africa,
but the uptake of contraceptives is average to low with resultant soaring of
unplanned pregnancy and rising statistics of termination of pregnancy (TOP)
services. This study aimed to establish the contraceptive practices among women
in the South African population seeking TOP in one public hospital in Eastern
Cape, South Africa. METHODS: A cross-sectional study was carried out among women
seeking TOP in a women's clinic. Self-administered questionnaires were used as
data collection tool, and the data collected were entered into SPSS software for
analysis, using descriptive statistics to calculate frequencies and percentages
while chi-square test was used to determine the associations between the socio
demography and contraceptive practices of the participants. RESULTS: Majority of
the women were aged between 20 and 29 years, had secondary education, unemployed,
single and resided in townships. Contraceptive uptake prior to termination of
pregnancy (CTOP) among them was 44.1%, but 85.8% had good contraceptives
knowledge. Their contraceptive practices are determined by partner's opinion,
source and availability of contraceptives, previous CTOP, side effect of
contraceptives and having children. Age group, educational level and employment
status were found to be related to the contraceptive practices of the
participants but were not statistically significant. CONCLUSION: To reduce
unplanned pregnancies and subsequent number of women seeking CTOP, the socio
economic factors associated with contraceptive practices as well as the
programmes, policies and guidelines of contraceptives need to be improved on for
any improvement on the factors determining contraceptive practices.
PMID- 27608677
TI - The use of e-health and m-health tools in health promotion and primary prevention
among older adults: a systematic literature review.
AB - BACKGROUND: The use of e-health and m-health technologies in health promotion and
primary prevention among older people is largely unexplored. This study provides
a systematic review of the evidence on the scope of the use of e-health and m
health tools in health promotion and primary prevention among older adults (age
50+). METHODS: A systematic literature review was conducted in October 2015. The
search for relevant publications was done in the search engine PubMed. The key
inclusion criteria were: e-health and m-health tools used, participants' age 50+
years, focus on health promotion and primary prevention, published in the past 10
years, in English, and full-paper can be obtained. The text of the publications
was analyzed based on two themes: the characteristics of e-health and m-health
tools and the determinants of the use of these tools by older adults. The quality
of the studies reviewed was also assessed. RESULTS: The initial search resulted
in 656 publications. After we applied the inclusion and exclusion criteria, 45
publications were selected for the review. In the publications reviewed, various
types of e-health/m-health tools were described, namely apps, websites, devices,
video consults and webinars. Most of the publications (60 %) reported studies in
the US. In 37 % of the publications, the study population was older adults in
general, while the rest of the publications studied a specific group of older
adults (e.g. women or those with overweight). The publications indicated various
facilitators and barriers. The most commonly mentioned facilitator was the
support for the use of the e-health/m-health tools that the older adults
received. CONCLUSIONS: E-health and m-health tools are used by older adults in
diverse health promotion programs, but also outside formal programs to monitor
and improve their health. The latter is hardly studied. The successful use of e
health/m-health tools in health promotion programs for older adults greatly
depends on the older adults' motivation and support that older adults receive
when using e-health and m-health tools.
PMID- 27608678
TI - Ethiopian teachers: their knowledge, attitude and practice towards epilepsy.
AB - BACKGROUND: In Ethiopia where the burden of epilepsy is highest among school age
children and teenagers, and where people with epilepsy (PWE) and their relatives
suffers from high level of perceived stigma, there had not been any study that
assessed the knowledge, attitude and practice of teachers towards PWE. This study
aims to assess and understand the social and demographic determinants of
knowledge, attitude and practice of teachers towards PLW in Addis Ababa,
Ethiopia. METHODS: Multistage cluster sampling procedure was used to identify
twenty schools from three sub cities of Addis Ababa, Ethiopia. Standardized self
administered questionnaire was used to collect data from 845 volunteer teachers
in the pre identified schools. Frequencies were used to characterize the
demographic variables while multiple response frequencies were used to
characterize the multiple response variable sets. Non-parametric statistical
methods were used to describe the association among the demographic variables of
interest and the count sums of multiple response variables which were grouped
into biologically and culturally plausible responses. RESULTS: The most common
biologically plausible responses were: brain diseases (26.5 %) from causes, allow
my offspring to play with PWE (19.1 %) from attitude, protect the subject from
injury (20.4 %) from first aid measures and seek help from medical doctors (52.2
%) from epilepsy treatment. On the contrary, the most common culturally plausible
responses were: psychiatric illness (12.9 %) from causes, epilepsy be cured
before attendance to school (21.6 %) from attitude, smelling the smoke of struck
match (14.2 %) from first aid measures and Holy water treatment (20.3 %) from
epilepsy treatment suggestions. The biologically and culturally plausible
responses were negatively correlated. Level of education was positively
associated with biologically plausible responses while teaching experience was
negatively correlated with culturally plausible responses. CONCLUSION: A high
percentage of teachers in Addis Ababa considered epilepsy as a psychiatric
illness closely linked to insanity. This explains their suggestions of Holy water
treatment and Church healing sessions as epilepsy remedies. This is in agreement
with Ethiopian culture, in which evil spirit and insanity are believed to be
better treated by religious remedies than with modern medical treatments.
Incorporating special needs educational training courses in the curriculum of
teachers training may help them shift their knowledge, attitudes and practices
from that of the culturally plausible to biologically plausible one.
PMID- 27608680
TI - Health promotion targeting older people.
PMID- 27608679
TI - Rate, timing and predictors of relapse in patients with anorexia nervosa
following a relapse prevention program: a cohort study.
AB - BACKGROUND: Relapse is common among recovered anorexia nervosa (AN) patients.
Studies on relapse prevention with an average follow-up period of 18 months found
relapse rates between 35 and 41 %. In leading guidelines there is general
consensus that relapse prevention in patients treated for AN is a matter of
essence. However, lack of methodological support hinders the practical
implementation of relapse prevention strategies in clinical practice. For this
reason we developed the Guideline Relapse Prevention Anorexia Nervosa. In this
study we examine the rate, timing and predictors of relapse when using this
guideline. METHOD: Cohort study with 83 AN patients who were enrolled in a
relapse prevention program for anorexia nervosa with 18 months follow-up. Data
were analyzed using Kaplan-Meijer survival analyses and Cox regression. RESULTS:
Eleven percent of the participants experienced a full relapse, 19 % a partial
relapse, 70 % did not relapse. Survival analyses indicated that in the first four
months of the program no full relapses occurred. The highest risk of full relapse
was between months 4 and 16. None of the variables remained a significant
predictor of relapse in the multivariate Cox regression analysis. CONCLUSION: The
guideline offers structured procedures for relapse prevention. In this study the
relapse rates were relatively low compared to relapse rates in previous studies.
We recommend that all patients with AN set up a personalized relapse prevention
plan at the end of their treatment and be monitored at least 18 months after
discharge. It may significantly contribute to the reduction of relapse rates.
PMID- 27608681
TI - Taking a holistic approach to managing difficult stress fractures.
AB - Stress fractures and other bony stress injuries occur along a spectrum of
severity which can impact treatment and prognosis. When treating these injuries,
it should be borne in mind that no two stress fractures behave exactly alike.
Given that they are not a consistent injury, standardized treatment protocols can
be challenging to develop. Treatment should be individualized to the patient or
athlete, the causative activity, the anatomical site, and the severity of the
injury. A holistic approach to the treatment of the most difficult stress
fractures should be taken by orthopedists and sports medicine specialists. This
approach is necessary to obtain optimal outcomes, minimize loss of fitness and
time away from sports participation, and decrease the risk of recurrence.
PMID- 27608682
TI - Impact of impaired fractional flow reserve after coronary interventions on
outcomes: a systematic review and meta-analysis.
AB - BACKGROUND: FFR is routinely used to guide percutaneous coronary interventions
(PCI). Visual assessment of the angiographic result after PCI has limited
efficacy. Even when the angiographic result seems satisfactory FFR after a PCI
might be useful for identifying patients with a suboptimal interventional result
and higher risk for poor clinical outcome who might benefit from additional
procedures. The aim of this meta-analysis was to investigate available data of
studies that examined clinical outcomes of patients with impaired vs.
satisfactory fractional flow reserve (FFR) after percutaneous coronary
interventions (PCI). METHODS: This meta-analysis was carried out according to the
Cochrane Handbook for Systematic Reviews. The Mantel-Haenszel method using the
fixed-effect meta-analysis model was used for combining the results. Studies were
identified by searching the literature through mid-January, 2016, using the
following search terms: fractional flow reserve, coronary circulation, after,
percutaneous coronary intervention, balloon angioplasty, stent implantation, and
stenting. Primary endpoint was the rate of major adverse cardiac events (MACE).
Secondary endpoints included rates of death, myocardial infarction (MI), repeated
revascularisation. RESULTS: Eight relevant studies were found including a total
of 1337 patients. Of those, 492 (36.8 %) had an impaired FFR after PCI, and 853
(63.2 %) had a satisfactory FFR after PCI. Odds ratios indicated that a low FFR
following PCI was associated with an impaired outcome: major adverse cardiac
events (MACE, OR: 4.95, 95 % confidence interval [CI]: 3.39-7.22, p <0.001);
death (OR: 3.23, 95 % CI: 1.19-8.76, p = 0.022); myocardial infarction (OR:
13.83, 95 % CI: 4.75-40.24, p <0.0001) and repeated revascularisation (OR: 4.42,
95 % CI: 2.73-7.15, p <0.0001). CONCLUSIONS: Compared to a satisfactory FFR, a
persistently low FFR following PCI is associated with a worse clinical outcome.
Prospective studies are needed to identify underlying causes, determine an
optimal threshold for post-PCI FFR, and clarify whether simple additional
procedures can influence the post-PCI FFR and clinical outcome.
PMID- 27608683
TI - Poor sleep and reduced quality of life were associated with symptom distress in
patients receiving maintenance hemodialysis.
AB - BACKGROUND: The quality of life in patients receiving chronic hemodialysis is
compromised despite of the substantial achievements in treatments. Quality of
life in hemodialysis patients have been shown to be associated with decreased
survival and increased hospitalization. Therefore, it is necessary to incorporate
the managements of symptoms and patient self-perceived well-being as measurements
of effective treatments for these patients. METHODS: A survey of symptom
distress, quality of sleep and quality of life was performed in 301 maintenance
hemodialysis patients using Dialysis Symptom Index, Short Form-36, and Pittsburgh
Quality of Sleep Index table. Patients were recruited from five hospitals in
Guangdong area of China by convenience sampling. RESULTS: The prevalence of
various symptoms in maintenance hemodialysis patients was between 23.3 and 80.4
%. These patients had compromised sleep and poor quality of life. Moreover, poor
quality of sleep and impaired quality of life were associated with high symptom
burden of these patients. CONCLUSION: The patients receiving chronic hemodialysis
generally have heavy symptom distress, which could contribute to the disturbed
sleep and impaired quality of life of these patients. Measurements of clinical
outcomes for hemodialysis patients should include the management of symptoms and
morbidity. The ultimate goal of treatments is to improve patient self-perceived
quality of life.
PMID- 27608685
TI - Prolonged Mechanical Ventilation (PMV): When is it Justified in ICU?
AB - Over years, the number of patients requiring prolonged mechanical ventilation
(PMV) in ICU has increased. Trends in the numbers of patients requiring PMV are
of interest to health service planners because they consume a disproportionate
amount of healthcare resources, and have high illness costs.1 PMV is defined as
need of invasive mechanical ventilation for consecutive 21 days for at least 6
hours per day. With improvement in ICU care more patients survive acute
respiratory failure and with that number of patients requiring PMV is likely to
increase further. In a large multi centric study in United Kingdom the incidence
PMV was 4.4 per 100 ICU admissions, and 6.3 per 100 ventilated ICU admissions.
Also these patients used 29.1% of all general ICU bed days, had longer hospital
stay after ICU discharge than non-PMV patients and had higher hospital mortality
(40.3% vs 33.8%, P = 0.02).2.
PMID- 27608686
TI - Clinical Profile of Patients Requiring Prolonged Mechanical Ventilation and their
Outcome in a Tertiary Care Medical ICU.
AB - INTODUCTION: An increasing number of patients require mechanical ventilation and
there has been a proportional increase in patients needing prolonged mechanical
ventilation (ventilated for >= 21 days, for atleast 6 hours per day). It accounts
for about 10% of all mechanically ventilated patients. Although these patients
represent a smaller proportion of intensive care unit (ICU) patients, they
consume substantial ICU resources. We studied etiology, metabolic and clinical
profile, complications and outcome of these patients. METHODS: This was a
prospective observational study in the medical ICUs of a tertiary hospital over
18 months. All patients above 12 years of age requiring prolonged invasive
mechanical ventilation were recruited. Detailed clinical and laboratory records
were noted. Sequential Organ Failure Assessment (SOFA) score was calculated on
admission. RESULTS: Of a total 1150 patients who were admitted in ICU during
study duration, 34.5% (n= 397) needed mechanical ventilation and 3.91% (n=45)
required prolonged mechanical ventilation. Most common patient subsets were:
acute inflammatory demyelinating polyneuropathy (AIDP) 28.50% (n=13), cerebro
vascular accident (CVA): 17.30% (n=8), tetanus 8.60% (n=4) and acute respiratory
distress syndrome (ARDS) 6.50% (n=3). The mean age of patients was 32 years.
Electrolyte imbalances observed were hypocalcaemia (84.44%), hypomagnesaemia
(40.9%), hypokalemia (31.11%) and hypophosphatemia (23.8%). Ventilator-associated
pneumonia (VAP) (53.33%) was the most frequent complication, followed by
decubitus ulcers (40%) and deep vein thrombosis (8.89%). Mean duration of ICU
stay was 57.02 days +/- 44.73 days. Twenty six out of 45 patients (57.75%) were
successfully weaned off ventilator support and discharged from the hospital. The
SOFA score of patients who survived (mean 2.15) was lesser than that of patients
who expired (mean 2.89) (p= 0.36, ns). CONCLUSIONS: The incidence of prolonged
mechanical ventilation in our study was 3.91% of total 1150 ICU admissions and
11.3% of the 397 patients requiring invasive mechanical ventilation. AIDP, CVA,
tetanus and ARDS were the most common diagnoses. Survival in the study population
was 57.75%. VAP was the most common complication. High incidence of
hypocalcaemia, hypomagnesaemia, hypokalemia and hypophosphatemia was noted in
patients requiring prolonged mechanical ventilation.
PMID- 27608684
TI - Convergent validity: agreement between accelerometry and the Global Physical
Activity Questionnaire in college-age Saudi men.
AB - BACKGROUND: The Global Physical Activity Questionnaire (GPAQ) has been
recommended for the international tracking of physical activity (PA). This study
aimed to investigate the agreement between the GPAQ and accelerometry, as well as
the test-retest reliability of the GPAQ in Saudi college-age men. METHODS: The
participants included 62 male students, aged 20.0 +/- 1.1 year, with a mean body
mass index (BMI) of 24.1 +/- 6.3 kg/m(2). This study used a cross-sectional
comparison of measures design. Participants completed the GPAQ twice (2 weeks
apart) and wore accelerometers for seven consecutive days. RESULTS: The agreement
between the GPAQ and accelerometry for moderate to vigorous PA (MVPA) was weak (r
<= 0.32). Participants underreported sedentary time relative to accelerometer
measurements (? = 3.4 h/day). BMI was statistically associated with increased
bias between the two methods. However, correlations between the GPAQ test and
retest for MVPA and sedentary time were moderate to strong (r = 0.44-0.78).
CONCLUSION: The GPAQ is reliable, but had low agreement with accelerometry for
estimating MVPA, and very low agreement with accelerometry for estimating
sedentary time in college-age Saudi men. Individual participant characteristics
should be considered when using the GPAQ to estimate sedentary time. Adapting the
current GPAQ to build a regional PA questionnaire is recommended.
PMID- 27608687
TI - A Cross-Sectional Observational Study to Determine the Prevalence of Insomnia
amongst Indian Corporate Employees.
AB - OBJECTIVES: To determine the prevalence of insomnia, co-morbid medical
conditions, personal habits and impact of insomnia on various day-to-day
activities among corporate employees. DESIGN: This was a cross-sectional,
observational study conducted in six corporate offices. SETTING: A corporate
office was defined as any organized body performing various business operations
and working together to achieve a common goal. PARTICIPANTS: Six hundred and five
office based employees of Indian nationality who were 18 years or above and
working approximately 8 hours a day were enrolled for this study.
PMID- 27608688
TI - To Study Endothelial Dysfunction in Rheumatoid Arthritis.
AB - BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased morbidity
and mortality. This excess mortality attributable to cardiovascular events.
Endothelial dysfunction represents the earliest stage of atherosclerosis. It can
be measured noninvasively by peripheral tests of function, such as pulse wave
analysis. OBJECTIVES: To evaluate the influence of chronic inflammatory state on
endothelial function in patients with RA free of cardiovascular disease or risk
factors by measuring endothelial reactivity. METHOD: A total number of 62
patients of RA and 18 normal healthy controls participated in the study. The
pulse wave velocity (PWV), reflection index (RI) and augmentation or stiffness
Index (SI) were measured at baseline and vasodilatory response was measured.
Waveform analyzer and Micromedical Pulse Trace Analyser were used. RESULTS: Heart
brachial PWV and brachial ankle PWV were not statistically significant in healthy
and RA patient groups. RI was higher in RA patients than controls. SI in RA
patient group (7.94 +/- 1.20) was statistically significant (p < .0001) as
compared to healthy controls (6.75 +/- 0.65). RA patients with low SI had active
disease indicated by DAS28 (5.03 +/- 1.20) increased ESR and CRP levels as
compared to the controls. CONCLUSIONS: RA with high disease activity, free from
cardiovascular risk factors and overt cardiovascular disease had premature aging
(increased vascular stiffness). Inflammatory process associated with RA was
responsible for findings. It is suggested that the increased arterial stiffness
contributes to the observed increased cardiovascular mortality and morbidity in
subjects with RA.
PMID- 27608689
TI - Prevalence of Risk Factors of Diabetes Among Urban Poor South Indian Population.
AB - OBJECTIVE: The objective of the study was to assess the prevalence of risk
factors of diabetes among urban poor population in Chennai, Tamil Nadu, South
India. STUDY AND METHODS: A cross-sectional study was conducted from Dec-2010 to
Feb-2011 in Chennai city. Five hundred twenty-nine subjects aged above 18 years
(409 women and 120 men) habitants of three slums were randomly selected. A
structured questionnaire was used to collect the socio-demographic and clinical
information. Anthropometric measures, blood pressure and random blood glucose
(RCBG) estimation were done. Dietary intake was assessed using 24-hour diet
recall and duration of physical activity/day in all components was recorded.
RESULTS: The mean age and BMI of the study population was 45.4+/-12.8 years and
25.8+/-4.9 kg/m2 respectively. About 20.4% were illiterate and 34.8% were either
unemployed, retired or housewives. Median family income per month was 3000 INR.
Prevalence of obesity (>=25 kg/m2) was 57.3% and central obesity (>=90 cms in
male and >=80 cms in female) was 75.7%. The median duration spent in walking,
standing and sitting were 30, 120, and 240 minutes/day respectively. There was a
gross inadequacy in vegetable intake. The prevalence of self-reported diabetes
and hypertension was 20.8% and 24.2%, respectively. Among the subjects without a
previous diagnosis of diabetes, 12.5% had RCBG >=140 mgs. 10.6% were diagnosed
with hypertension. CONCLUSIONS: Sedentarism coupled with unhealthy diet pattern
are the major contributing factors for the higher prevalence of diabetes and
hypertension in urban poor population.
PMID- 27608690
TI - Cardiovascular Diseases Risk Prediction by Homocysteine in Comparison to other
Markers: A Study from Madhya Pradesh.
AB - INTRODUCTION: Atherosclerosis is associated with increased inflammatory activity
and risk of vascular disease. However, the factors that promote inflammation are
not apparently clear. In the present study we aimed to evaluate levels of
homocysteine in comparison with other markers including inflammatory risk
predictor of cardiovascular disease. METHODS: A total of 200 patients were
included in the study, of these 100 were angiographically proven cardiovascular
disease patients and 100 were not suffering from any cardiovascular disease.
Levels of homocysteine, hs-CRP, lipoprotein(a), HbA1c and blood lipid were
measured along with anthropometric and demographic parameters. RESULTS: Levels of
homocysteine and other markers were significantly increased in diseased group in
comparisons to control. CONCLUSION: There is a very high sensitivity,
specificity, and accuracy with 89% positive predictive value and 39.48 odds ratio
for homocysteine in cardiovascular patients when compared to other risk factors.
PMID- 27608691
TI - Recent Advances in Psoriatic Arthritis from Obscurity to Prominence.
AB - Psoriatic arthritis is a fascinating inflammatory arthritis. Till recently it did
not generate interest for lack of understanding of its immunopathology, and lack
of effective treatment. This has changed. PsA is now one of the hot topics - all
due to elucidation of genetic susceptibility associations, immunopathogenesis and
availability of effective therapy. In this communication we provide an overview
of these aspects of psoriatic arthritis.
PMID- 27608693
TI - Using Tables and Graphs for Reporting Data.
AB - For presenting the study results, authors need to choose from one of the three
formats: text, tables and graphs. The underlying consideration of any author
while making the choice is to ensure that readers find it easy to understand, to
assist the author present data in a way that would catch the reader's eye, hold
his interest and enhance his understanding. The choice should, therefore, be
based on the advantages and limitations of each of these formats. Most of the
observations are reported in textual format. Tables are useful when comparisons
are to be shown. Graphs attract readers' attention better and the data they
depict remains in the reader's memory. The type of graph used is dependent upon
the nature of data that is to be shown. Every research paper has a lot to say
through the data that has been collected and analyzed. However, this data needs
to be presented in a logical, coherent and easy-to-understand manner. The way
data is presented can influence the reviewers' and editors' decision. It can also
make the difference between a paper being appreciated by the readers or being
neglected or even trashed by them. Tables and Graphs are the two important tools
that authors use to make the data more presentable and easy to read and
understand.
PMID- 27608692
TI - Pancreas and Diabetes Mellitus: The Relationship between the Organ and the
Disease.
AB - Diabetes mellitus has been a fascinating disease from the dawn of medical
history. The first breakthrough in its treatment came in 1922, with the discovery
of insulin which was extracted from the pancreas of a dog. Even earlier, a
relationship between pancreas and diabetes mellitus had been suspected by medical
scientists. However, the study of diabetes mellitus is much more than its
relationship with the pancreas. On the other hand the pancreas has been known to
be a very reclusive organ that is hidden away from physicians and surgeons for
centuries. In recent times, it has become more accessible and has yielded some of
its secrets. The relationship between the pancreas and diabetes mellitus is a
story full of complexities and surprises. This article attempts to reveal some of
the important events and persons in the story and the controversies surrounding
them.
PMID- 27608694
TI - Dupuytren's Contracture Associated with Long-Standing Diabetes Mellitus.
PMID- 27608695
TI - Low Backache as Initial Presentation of Acute Lymphoblastic Leukemia.
PMID- 27608696
TI - Recurrent Hypoglycaemia due to Insulin Autoimmune Disease (Hirata Disease)
Associated with Monoclonal Gammopathy of Unknown Significance.
AB - Hirata disease is a rare disease characterised by recurrent episodes of
hypoglycaemia due to anti-insulin antibody. In most of these cases causative
agents were sulfhydryl containing compounds like Penicillamine, Glutathione, and
Methimazole. The presentation of disease closely mimics insulinoma. We report 52
years female patient presenting with recurrent episodes of hypoglycaemia due to
anti-insulin antibody. On evaluation, underlying cause of antibody was found to
be monoclonal gammopathy of unknown significance (MGUS).
PMID- 27608697
TI - Acute Myeloid Leukemia Presenting as Intracerebral Granulocytic Sarcoma.
AB - The CNS involvement of acute myeloid leukemia (AML) is more commonly manifest as
meningeal involvement. Rarely it may present as intravascular tumor aggregates
called granulocytic sarcoma which presents as intracranial hemorrhage. We are
presenting a case of intracranial, intra-parenchymal granulocytic sarcoma (other
names: chloroma, extramedullary myeloblastoma), presenting as acute hemiplegia
without cerebral hemorrhage.
PMID- 27608698
TI - Families of Pseudohypoparathyroidism presenting as Seizure.
AB - Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders
characterized by variable insensitivity to parathyroid hormone. We describe two
cases of 22 year male and 24 year female who have typical clinical features of
Albright's hereditary osteodystrophy (AHO). Laboratory investigation revealed
evidence of pseudohypoparathyroidism and skeletal survey showed shortening of the
metacarpals and metatarsals.
PMID- 27608699
TI - Gastric Mucormycosis with Hemolytic Uremic Syndrome.
AB - Mucormycosis, is an emerging fungal infection in immunocompromised and diabetic
individuals, usually affects rhino-orbito-cerebral, cutaneous and pulmonary
regions. But mucormycosis in immunocompetent environment is rare and occurrence
of gastric mucormycosis is unusual. We report a case of 19 year old female, with
no pre-existing co-morbidities, presented with fever, dysentery, vomiting, and
melena for 4 days. On evaluation she was found to have pancytopenia, acute kidney
injury, hemolytic anemia, coagulopathy and hepatic derangement and treated with
hemodialysis, plasmapheresis along with antibiotics and packed cell RBC
transfusion. Upper gastrointestinal endoscopy revealed presence of extensive
esophageal and gastric ulcer. In view of persistent bleeding despite endoscopic
sclerotherapy, repetition of upper gastrointestinal endoscopy and CT abdomen with
oral contrast was done, which revealed perforated gastric ulcer. Exploratory
laparotomy and excision of ulcer was done. The biopsy of gastric ulcer had shown
the presence of granulomatous necrotic areas positive for mucormycosis. Then she
was managed with amphotericin-B, posoconazole with which she improved.
PMID- 27608700
TI - Systemic Lupus Erythematosus Presenting as Neuroretinitis.
AB - Neuroretinitis is the inflammation of retina and optic nerve. It is associated
with optic disc edema accompanied by peripapillary or macular hard exudates. A 17
yr old female presented with headache and nausea of five days duration. She had
periorbital edema and mild splenomegaly. Neurological assessment was non
contributory. She was found to have pancytopenia, albuminuria and a high ESR.
Thereafter she developed blurring of vision of both eyes. Opthalmological
examination showed it to be due to bilateral neuroretinitis. ANA and anti-ds DNA
were strongly positive. Renal biopsy with immunofluorescence study revealed
diffuse global proliferative lupus nephritis with active lesions [class IV-G
(A)]. She was diagnosed as a case of SLE presenting with neuroretinitis.
PMID- 27608701
TI - Right Ventricular Myxoma.
AB - We report a case of 30 year female who presented with complaints of intermittent
chest pain and breathlessness for 8 months, Diagnosed to have right ventricular
mass protruding into main pulmonary artery during each systole. The mass was
completely excised. Histopathological examination showed myxoma.
PMID- 27608702
TI - Isolated Subclavian Artery Thrombosis.
AB - We presume this case to highlight the importance of underestimated percutaneous
angioplasty with stent in isolated subclavian artery thrombosis.
PMID- 27608703
TI - Malignant Pericardial Tamponade in a Case of Signet Cell Gastric Carcinoma.
AB - We report a case of gastric signet cell carcinoma, presenting as cardiac
tamponade, in a young male patient. The diagnosis of gastric signet cell
carcinoma was confirmed by immunohistochemistry of the lymph node specimen in our
patient.
PMID- 27608704
TI - Hurler Scheie Disease.
AB - We present a very rare case of mucopolysaccharidosis type I (MPS I) which
presented to us with respiratory distress. Our patient had short stature, coarse
facial features, claw hands and clouding of both corneae. This article highlights
the salient features present in a case of mucopolysaccharidosis type I.
PMID- 27608705
TI - Extra-Pontine Myelinolysis in a Case of Pan-hypopituitarism Due to Empty Sella
Syndrome.
AB - Rapid correction of hyponatremia is known to cause central pontine myelinolysis
(CPM). It may concurrently involve other areas of brain as well, referred as
extra-pontine myelinolysis (EPM). Isolated EPM however is a very rare occurrence.
We present a case of EPM where the hyponatremia was secondary to hypothyroidism
due to empty sella syndrome. Chronic hyponatremia should always be corrected
slowly to avoid such osmotic myelinolysis syndromes (OMS).
PMID- 27608707
TI - Dracanculiasis (Guinea-worm): On the Verge of Eradication.
PMID- 27608706
TI - Pioneers in Enteric Infections.
PMID- 27608708
TI - Hypersensitivity Reactions in HIV Infected Individuals after Substitution of
Antiretroviral Drug Regimen: Need for Pharmacovigilance in the National Program.
PMID- 27608709
TI - Stress Management in Mothers of Students Appearing for Competitive Examinations
through Yoga - A Comparative Study.
PMID- 27608710
TI - Psychological Insulin Resistance in Patients with Type 2 Diabetes Mellitus.
PMID- 27608711
TI - Evidence for the presence of African swine fever virus in an endemic region of
Western Kenya in the absence of any reported outbreak.
AB - BACKGROUND: African swine fever (ASF), caused by African swine fever virus
(ASFV), is a severe haemorrhagic disease of pigs, outbreaks of which can have a
devastating impact upon commercial and small-holder pig production. Pig
production in western Kenya is characterised by low-input, free-range systems
practised by poor farmers keeping between two and ten pigs. These farmers are
particularly vulnerable to the catastrophic loss of livestock assets experienced
in an ASF outbreak. This study wished to expand our understanding of ASFV
epidemiology during a period when no outbreaks were reported. RESULTS: Two
hundred and seventy six whole blood samples were analysed using two independent
conventional and real time PCR assays to detect ASFV. Despite no recorded
outbreak of clinical ASF during this time, virus was detected in 90/277 samples
analysed by conventional PCR and 142/209 samples analysed by qPCR. Genotyping of
a sub-set of these samples indicated that the viruses associated with the
positive samples were classified within genotype IX and that these strains were
therefore genetically similar to the virus associated with the 2006/2007 ASF
outbreaks in Kenya. CONCLUSION: The detection of ASFV viral DNA in a relatively
high number of pigs delivered for slaughter during a period with no reported
outbreaks provides support for two hypotheses, which are not mutually exclusive:
(1) that virus prevalence may be over-estimated by slaughter-slab sampling,
relative to that prevailing in the wider pig population; (2) that sub-clinical,
chronically infected or recovered pigs may be responsible for persistence of the
virus in endemic areas.
PMID- 27608712
TI - Inequalities in the frequency of free sugars intake among Syrian 1-year-old
infants: a cross-sectional study.
AB - BACKGROUND: High frequency of free sugars intake, during the first year of life
is probably the greatest risk factor for early childhood caries. The latter is a
global public health challenge. Very little is known about the social
determinants of infant's frequency of free sugars intake, particularly in low
income countries. Thus, the present study aimed to assess the association between
the frequency of free sugars intake among 1-year-old Syrian infants and each of
parents' socioeconomic position (SEP), maternal frequency of free sugars intake
and knowledge of infant's oral health behaviour. METHODS: Using a cross-sectional
design, 323 1-year-old infants, attending vaccination clinics in 3 maternal and
child health centres (MCHCs) in Damascus, Syria, were selected. A systematic
random sampling was applied using the MCHCs' monthly vaccination registries. The
3 MCHCs were located in affluent, moderate and deprived areas. Infants' mothers
completed a structured questionnaire on socio-demographics, infant's and mother's
frequency of free sugars intake from cariogenic foods and beverages, and mother's
knowledge about infant's oral health behaviour. Binary and multiple regression
analyses were performed. The level of significance was set at 5 %. RESULTS: The
response rate was 100 %. Overall, 42.7 % of infants had high frequency of free
sugars intake (>4times a day). Infants whose fathers were not working were more
likely to have high frequency of free sugars intake. Similarly, infants whose
mothers had low level of knowledge about infant's oral health behaviour, or high
frequency of free sugars intake were more likely to have high frequency of free
sugars intake. The association between father's occupation and infant's frequency
of free sugars intake attenuated after adjustment for mother's knowledge and
frequency of free sugars intake (adjusted OR = 1.5, 1.8, 3.2; 95%CI = 0.5-4.8,
1.1-3, 1.4-7.4; respectively). CONCLUSIONS: There are socioeconomic inequalities
in the frequency of free sugars intake among Syrian 1-year-old infants.
Integrated pre/post-natal interventions, targeting mothers from low SEP and
aiming at reducing their free sugars intake and improving their knowledge about
infant's oral health behaviour, will potentially reduce socioeconomic
inequalities in infant's frequency of free sugars intake.
PMID- 27608713
TI - Paediatric non-progression following grandmother-to-child HIV transmission.
AB - BACKGROUND: In contrast to adult HIV infection, where slow disease progression is
strongly linked to immune control of HIV mediated by protective HLA class I
molecules such as HLA-B*81:01, the mechanisms by which a minority of HIV-infected
children maintain normal-for-age CD4 counts and remain clinically healthy appear
to be HLA class I-independent and are largely unknown. To better understand these
mechanisms, we here studied a HIV-infected South African female, who remained a
non-progressor throughout childhood. RESULTS: Phylogenetic analysis of viral
sequences in the HIV-infected family members, together with the history of grand
maternal breast-feeding, indicated that, unusually, the non-progressor child had
been infected via grandmother-to-child transmission. Although HLA-B*81:01 was
expressed by both grandmother and grand-daughter, autologous virus in each
subject encoded an escape mutation L188F within the immunodominant HLA-B*81:01
restricted Gag-specific epitope TL9 (TPQDLNTML, Gag 180-188). Since the
transmitted virus can influence paediatric and adult HIV disease progression, we
investigated the impact of the L188F mutant on replicative capacity. When this
variant was introduced into three distinct HIV clones in vitro, viral replicative
capacity was abrogated altogether. However, a virus constructed using the gag
sequence of the non-progressor child replicated as efficiently as wildtype virus.
CONCLUSION: These findings suggest alternative sequences of events: the
transmission of the uncompensated low fitness L188F to both children, potentially
contributing to slow progression in both, consistent with previous studies
indicating that disease progression in children can be influenced by the
replicative capacity of the transmitted virus; or the transmission of fully
compensated virus, and slow progression here principally the result of HLA
independent host-specific factors, yet to be defined.
PMID- 27608714
TI - RNA-Seq analysis of seasonal and individual variation in blood transcriptomes of
healthy managed bottlenose dolphins.
AB - BACKGROUND: The blood transcriptome can reflect both systemic exposures and
pathological changes in other organs of the body because immune cells recirculate
through the blood, lymphoid tissues, and affected sites. In human and veterinary
medicine, blood transcriptome analysis has been used successfully to identify
markers of disease or pathological conditions, but can be confounded by large
seasonal changes in expression. In comparison, the use of transcriptomic based
analyses in wildlife has been limited. Here we report a longitudinal study of
four managed bottlenose dolphins located in Waikoloa, Hawaii, serially sampled
(approximately monthly) over the course of 1 year to establish baseline
information on the content and variation of the dolphin blood transcriptome.
RESULTS: Illumina based RNA-seq analyses were carried out using both the Ensembl
dolphin genome and a de novo blood transcriptome as guides. Overall, the blood
transcriptome encompassed a wide array of cellular functions and processes and
was relatively stable within and between animals over the course of 1 year.
Principal components analysis revealed moderate clustering by sex associated with
the variation among global gene expression profiles (PC1, 22 % of variance).
Limited seasonal change was observed, with < 2.5 % of genes differentially
expressed between winter and summer months (FDR < 0.05). Among the differentially
expressed genes, cosinor analysis identified seasonal rhythmicity for the
observed changes in blood gene expression, consistent with studies in humans.
While the proportion of seasonally variant genes in these dolphins is much
smaller than that reported in humans, the majority of those identified in
dolphins were also shown to vary with season in humans. Gene co-expression
network analysis identified several gene modules with significant correlation to
age, sex, or hematological parameters. CONCLUSIONS: This longitudinal analysis of
healthy managed dolphins establishes a preliminary baseline for blood
transcriptome analysis in this species. Correlations with hematological
parameters, distinct from muted seasonal effects, suggest that the otherwise
relatively stable blood transcriptome may be a useful indicator of health and
exposure. A robust database of gene expression in free-ranging and managed
dolphins across seasons with known adverse health conditions or contaminant
exposures will be needed to establish predictive gene expression profiles
suitable for biomonitoring.
PMID- 27608716
TI - Humidifier disinfectant lung injury, how do we approach the issues?
AB - A large portion of the Korean population has been exposed to toxic humidifier
disinfectants (HDs), and considering that the majority of the victims are
infants, the magnitude of the damage is expected to be considerably larger than
what has currently been revealed. The current victims are voicing problems caused
by various diseases, including but not limited to lung, upper respiratory tract,
cardiovascular, kidney, musculoskeletal, eye, and skin diseases, etc. However,
there has been difficulty in gaining validation for these health problems and
identifying causal relationships due to lack of evidence proving that toxic HD is
the specific causes of extrapulmonary diseases such as allergic rhinitis.
Furthermore, the victims and bereaved families of the HD case have not received
any support for psychological distress such as post-traumatic stress disorder,
depression, feelings of injustice, and anger caused by the trauma. In addition,
because the underlying mechanisms of the toxic materials within the HDs such as
polyhexamethylene guanidine phosphate, poly(oxyalkylene guanidine) hydrochloride,
chloromethylisothiazolinone/methylisothiazolinone have yet to be determined, the
demand for information regarding the HD issue is growing. The victims of the HD
cases require support that goes beyond financial aid for medical costs and living
expenses. There is a desperate need for government-led integrated support centers
that provide individualized support through health screenings; in other words, we
need an integrated facility that provides the appropriate social support to allow
the victims to recover their physical and mental health, so as to well prepare
them to return to a normal life. The implementation of such a plan requires not
only the close cooperation between those departments already directly involved
such as the Ministry of Environment and the Ministry of Health and Welfare, but
also active support on a national scale from pan-governmental consultative
bodies.
PMID- 27608717
TI - Risk factors associated with depression and suicidal ideation in a rural
population.
AB - OBJECTIVES: This study aimed to evaluate the risk factors associated with
depression and suicidal ideation in a rural population. METHODS: A survey was
conducted with 543 farmers from Chungcheongnam-do Province using the Center for
Epidemiologic Studies Depression Scale (CES-D) for depression, Lubben Social
Network Scale (LSNS) for social support, Swedish Q16 for neurotoxicity symptoms
and a survey tool for farmer's syndrome. RESULTS: After adjusting for
socioeconomic factors using logistic regression analysis, poor self-rated health,
low social support and neurotoxicity were positively associated with the risk of
depression (odds ratio [OR], 15.96; 95% confidence interval [CI], 3.11 to 81.97;
OR, 3.14; 95% CI, 1.26 to 7.82; and OR, 3.68; 95% CI, 1.08 to 12.57,
respectively). The risk of suicidal ideation significantly increased with low
social support, neurotoxicity and farmer's syndrome (OR, 2.28; 95% CI, 1.18 to
4.40; OR, 6.17; 95% CI, 2.85 to 13.34; and OR, 3.70; 95% CI, 1.51 to 9.07,
respectively). CONCLUSIONS: Given the overall results of this study, there is a
need to establish programs which can improve the health and social relationships
of farmers. Also, when farmers have neurological symptoms from pesticide exposure
and characteristic symptoms of farmer's syndrome, a monitoring system for
depression and suicide must be made available.Conclusions: Given the overall
results of this study, there is a need to establish programs which can improve
the health and social relationships of farmers. Also, when farmers have
neurological symptoms from pesticide exposure and characteristic symptoms of
farmer's syndrome, a monitoring system for depression and suicide must be made
available.
PMID- 27608715
TI - Plasma exosome microRNAs are indicative of breast cancer.
AB - BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to
their cancer-specific expression profiles. However, efforts to develop
circulating breast cancer biomarkers are challenged by the heterogeneity of
microRNAs in the blood. To overcome this challenge, we aimed to develop a
molecular profile of microRNAs specifically secreted from breast cancer cells.
Our first step towards this direction relates to capturing and analyzing the
contents of exosomes, which are small secretory vesicles that selectively
encapsulate microRNAs indicative of their cell of origin. To our knowledge,
circulating exosome microRNAs have not been well-evaluated as biomarkers for
breast cancer diagnosis or monitoring. METHODS: Exosomes were collected from the
conditioned media of human breast cancer cell lines, mouse plasma of patient
derived orthotopic xenograft models (PDX), and human plasma samples. Exosomes
were verified by electron microscopy, nanoparticle tracking analysis, and western
blot. Cellular and exosome microRNAs from breast cancer cell lines were profiled
by next-generation small RNA sequencing. Plasma exosome microRNA expression was
analyzed by qRT-PCR analysis. RESULTS: Small RNA sequencing and qRT-PCR analysis
showed that several microRNAs are selectively encapsulated or highly enriched in
breast cancer exosomes. Importantly, the selectively enriched exosome microRNA,
human miR-1246, was detected at significantly higher levels in exosomes isolated
from PDX mouse plasma, indicating that tumor exosome microRNAs are released into
the circulation and can serve as plasma biomarkers for breast cancer. This
observation was extended to human plasma samples where miR-1246 and miR-21 were
detected at significantly higher levels in the plasma exosomes of 16 patients
with breast cancer as compared to the plasma exosomes of healthy control
subjects. Receiver operating characteristic curve analysis indicated that the
combination of plasma exosome miR-1246 and miR-21 is a better indicator of breast
cancer than their individual levels. CONCLUSIONS: Our results demonstrate that
certain microRNA species, such as miR-21 and miR-1246, are selectively enriched
in human breast cancer exosomes and significantly elevated in the plasma of
patients with breast cancer. These findings indicate a potential new strategy to
selectively analyze plasma breast cancer microRNAs indicative of the presence of
breast cancer.
PMID- 27608718
TI - Relationship between residential district and health-related quality of life in
Chungnam industrial complex area.
AB - OBJECTIVES: This study aimed to evaluate the relationship between residential
district of people, such as power plant, steel-mill and petrochemical industries,
and health-related quality of life (HRQoL). METHODS: Using a cross-sectional
study design, we randomly recruited participants for our study from industrial
areas (thermoelectric power plant, steel-mill, petrochemical industry) and rural
areas. Logistic regression analysis was used to identify the relationships
between Euro quality of life-5 dimension (EQ-5D) scores and living region, while
controlling for sociodemographic characteristics. RESULTS: In adjusted model,
quality of life decreased with increasing category of age and were lower for
females than males. EQ-5D scores of people living in the vicinity of
thermoelectric power plant were significant lower than those of people living the
vicinity of comparison region (odds ratio, 1.59; 95% confidence interval, 1.00 to
2.53). CONCLUSIONS: Living region of thermoelectric power plant, was strongly
associated with scores on the EQ-5D. More research is needed to elucidate the
mechanisms which makes the relationship with the living regions and HRQoL.
PMID- 27608719
TI - Electrotransfection of Polyamine Folded DNA Origami Structures.
AB - DNA origami structures are artificial molecular nanostructures in which DNA
double helices are forced into a closely packed configuration by a multitude of
DNA strand crossovers. We show that three different types of origami structures
(a flat sheet, a hollow tube, and a compact origami block) can be formed in
magnesium-free buffer solutions containing low (<1 mM) concentrations of the
condensing agent spermidine. Much like in DNA condensation, the amount of
spermidine required for origami folding is proportional to the DNA concentration.
At excessive amounts, the structures aggregate and precipitate. In contrast to
origami structures formed in conventional buffers, the resulting structures are
stable in the presence of high electric field pulses, such as those commonly used
for electrotransfection experiments. We demonstrate that spermidine-stabilized
structures are stable in cell lysate and can be delivered into mammalian cells
via electroporation.
PMID- 27608720
TI - Psychological support for families of ICU patients: longitudinal documentation of
the service.
AB - This study is the first systematic effort to investigate psychological services
provided to relatives of ICU patients at Nicosia General Hospital. Documentation
of psychological sessions provided to relatives of ICU patients for the years
2011-2014 was analyzed. To investigate possible differences in the total number
of sessions for the referenced years, the records were analyzed using patients'
demographics, the outcome of hospitalization and the total number of sessions
with relatives. A questionnaire was sent to the ICU staff aiming to identify
their perception towards the need for psychological support. A total number of
863 psychological sessions were conducted with 640 relatives of 345 patients
hospitalized in the ICU. Results indicate that more sessions are recorded when
the outcome of younger patients' condition worsens, whereas the number of
sessions decreases for older patients' families. When comparing the personnel's
beliefs, regarding the importance of providing psychological services to
different age groups, significant difference was found suggesting that the older
the patient the less sessions they believe are required indicating a possible
ageism bias.
PMID- 27608721
TI - Lessons Learned for Online Health Community Moderator Roles: A Mixed-Methods
Study of Moderators Resigning From WebMD Communities.
AB - BACKGROUND: Online health community (OHC) moderators help facilitate
conversations and provide information to members. However, the necessity of the
moderator in helping members achieve goals by providing the support they need
remains unclear, with some prior research suggesting that moderation is
unnecessary or even harmful for close-knit OHCs. Similarly, members' perceptions
of moderator roles are underexplored. Starting January of 2013, WebMD moderators
stopped working for WebMD communities. This event provided an opportunity for us
to study the perceived role of moderators in OHCs. OBJECTIVE: We examine the OHC
members' perception on OHC moderators by studying their reactions toward the
departure of moderators in their communities. We also analyzed the relative
posting activity on OHCs before and after the departure of moderators from the
communities among all members and those who discussed moderators' departures.
METHODS: We applied a mixed-methods approach to study the posts of all 55
moderated WebMD communities by querying the terms relating to discussions
surrounding moderators' disappearance from the WebMD community. We performed open
and axial coding and affinity diagramming to thematically analyze patients'
reactions to the disappeared moderators. The number of posts and poster groups
(members and moderators) were analyzed over time to understand posting patterns
around moderators' departure. RESULTS: Of 821 posts retrieved under 95 threads, a
total of 166 open codes were generated. The codes were then grouped into 2 main
themes with 6 total subthemes. First, patients attempted to understand why
moderators had left and what could be done to fill the void left by the missing
moderators. During these discussions, the posts revealed that patients believed
that moderators played critical roles in the communities by making the
communities vibrant and healthy, finding solutions, and giving medical
information. Some patients felt personally attached with moderators, expressing
they would cease their community participation. On the other hand, patients also
indicated that moderators were not useful or sometimes even harmful for peer
interactions. The overall communities' posting activity, which was already in
decline, showed no significant difference before and after the moderators'
departure. In fact, the overall posting activities of the communities were
declining well before the moderators' departure. These declining posting
activities might be the reason why WebMD removed the moderators. CONCLUSION:
Compassionate moderators who provide medical expertise, control destructive
member posts, and help answer questions can provide important support for patient
engagement in OHCs. Moderators are in general received positively by community
members and do not appear to interfere with peer interactions. Members are well
aware of the possibility of misinformation spreading in OHCs. Further
investigation into the attitudes of less vocal community members should be
conducted.
PMID- 27608722
TI - End-point indicators of low-dose intra-tympanic gentamicin in management of
Meniere's disease.
AB - CONCLUSIONS: One-shot, low-dose intra-tympanic gentamicin (ITG) treatment was
effective and safe for Meniere's disease (MD) patients. Head thrust test (HTT)
and vestibular evoked myogenic potentials (VEMPs) test could be used as endpoint
indicators for vertigo control in MD patients. OBJECTIVES: The present study is
to explore end-point indicators of ITG injection in MD. METHODS: Patients with MD
were reviewed from June 2012 to March 2014. Single-shot ITG at a concentration of
30 mg/ml was administered to patients. The sensitivity and specificity of HTT and
VEMPs for vertigo control were measured. RESULTS: All 37 patients with a median
follow-up of 26 months were included. Of those 37 patients, 24 patients (64.9%)
obtained class A vertigo control and seven patients (18.9%) obtained class B
vertigo control. Only six patients had class C control (16.2%). The sensitivity
and specificity of HTT for vertigo control were 74.2% and 50.0%. Meanwhile, the
sensitivity and specificity of VEMPs threshold were 83.9% and 33.3%. When
combined HTT and VEMPs, sensitivity and specificity were 93.5% and 66.7%. Based
on the four-tone average thresholds at 0.5, 1, 2, 3 kHz, 78.4% patients had no
significant change in PTA and 16.2% patients experienced significant improvement.
PMID- 27608724
TI - Transcription of telomeric DNA leads to high levels of homologous recombination
and t-loops.
AB - The formation of DNA loops at chromosome ends (t-loops) and the transcription of
telomeres producing G-rich RNA (TERRA) represent two central features of
telomeres. To explore a possible link between them we employed artificial human
telomeres containing long arrays of TTAGGG repeats flanked by the T7 or T3
promoters. Transcription of these DNAs generates a high frequency of t-loops
within individual molecules and homologous recombination events between different
DNAs at their telomeric sequences. T-loop formation does not require a single
strand overhang, arguing that both terminal strands insert into the preceding
duplex. The loops are very stable and some RNase H resistant TERRA remains at the
t-loop, likely adding to their stability. Transcription of DNAs containing TTAGTG
or TGAGTG repeats showed greatly reduced loop formation. While in the cell
multiple pathways may lead to t-loop formation, the pathway revealed here does
not depend on the shelterins but rather on the unique character of telomeric DNA
when it is opened for transcription. Hence, telomeric sequences may have evolved
to facilitate their ability to loop back on themselves.
PMID- 27608726
TI - COME: a robust coding potential calculation tool for lncRNA identification and
characterization based on multiple features.
AB - Recent genomic studies suggest that novel long non-coding RNAs (lncRNAs) are
specifically expressed and far outnumber annotated lncRNA sequences. To identify
and characterize novel lncRNAs in RNA sequencing data from new samples, we have
developed COME, a coding potential calculation tool based on multiple features.
It integrates multiple sequence-derived and experiment-based features using a
decompose-compose method, which makes it more accurate and robust than other well
known tools. We also showed that COME was able to substantially improve the
consistency of predication results from other coding potential calculators.
Moreover, COME annotates and characterizes each predicted lncRNA transcript with
multiple lines of supporting evidence, which are not provided by other tools.
Remarkably, we found that one subgroup of lncRNAs classified by such supporting
features (i.e. conserved local RNA secondary structure) was highly enriched in a
well-validated database (lncRNAdb). We further found that the conserved
structural domains on lncRNAs had better chance than other RNA regions to
interact with RNA binding proteins, based on the recent eCLIP-seq data in human,
indicating their potential regulatory roles. Overall, we present COME as an
accurate, robust and multiple-feature supported method for the identification and
characterization of novel lncRNAs. The software implementation is available at
https://github.com/lulab/COME.
PMID- 27608728
TI - Biophysical experiments and simulation in nanoparticle-based drug delivery
systems.
AB - We are on the cusp of a new era in therapeutics which will be characterized by
drugs that can be individually tailored to a patient to be more effective and
less likely to cause side effects. One of the most successful ways to deliver
such drugs to the physiological site of interest involves embedding them in lipid
nanoparticles. Here we give a brief history of the development of lipid-based
drug carriers, emphasizing the role that biophysical characterization played in
their development. We further argue that in the future, the revolutionary gain in
power of computer simulation techniques will enable researchers to efficiently
identify optimal lipid nanoparticle compositions and physical characteristics for
experimental validation.
PMID- 27608729
TI - Relevance of sleep disturbance to the integrity and characteristics of secondary
peristalsis in patients with gastroesophageal reflux disease.
AB - OBJECTIVE: Sleep disturbance is common in patients with gastroesophageal reflux
disease (GERD). Secondary peristalsis is important for clearance of the refluxate
from the esophagus. We aimed to test the hypothesis whether secondary peristalsis
is impaired in GERD patients with sleep disturbance. METHODS: Secondary
peristalsis was stimulated with slow and rapid air injections into mid-esophagus
in 8 age-matched health controls and 41 patients with GERD. Sleep disturbance was
assessed by the Pittsburg Sleep Quality Index (PSQI). Objective sleep measures
were assessed by ambulatory actigraphy. RESULTS: The threshold volume for
inducing secondary peristalsis during slow air injection was significantly higher
in GERD patients with sleep disturbance than healthy controls (14.3 +/- 1.2 vs.
8.9 +/- 0.5 mL, p < .05). GERD patients with sleep disturbance had higher
threshold volume of secondary peristalsis during rapid air injection than GERD
patients without sleep disturbance (5.1 +/- 0.4 vs. 3.9 +/- 0.2 mL, p < .05) and
healthy controls (5.1 +/- 0.4 vs. 3.6 +/- 0.2 mL, p < .05). There was a negative
correlation between PSQI score and peristaltic frequency during rapid air
injection (r = -.39, p = .01). Secondary peristaltic amplitude during rapid air
injection was negatively correlated with wake after sleep onset (r = -.34, p =
.04). CONCLUSIONS: Sleep disturbance is associated with secondary peristaltic
response to distension-induced esophageal stimulation in patients with GERD. Our
study suggests that sleep disturbance per se may adversely influence the
effectiveness of esophageal peristalsis and bolus clearance during sleep in
patients with GERD.
PMID- 27608727
TI - Propagating Humanized BLT Mice for the Study of Human Immunology and
Immunotherapy.
AB - The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly
complete human immune system, therefore providing a powerful tool to study human
immunology and immunotherapy. However, its application is greatly limited by the
restricted supply of human CD34+ hematopoietic stem cells and fetal thymus
tissues that are needed to generate these mice. The restriction is especially
significant for the study of human immune systems with special genetic traits,
such as certain human leukocyte antigen (HLA) haplotypes or monogene
deficiencies. To circumvent this critical limitation, we have developed a method
to quickly propagate established BLT mice. Through secondary transfer of bone
marrow cells and human thymus implants from BLT mice into NSG (NOD/SCID/IL
2Rgamma-/-) recipient mice, we were able to expand one primary BLT mouse into a
colony of 4-5 proBLT (propagated BLT) mice in 6-8 weeks. These proBLT mice
reconstituted human immune cells, including T cells, at levels comparable to
those of their primary BLT donor mouse. They also faithfully inherited the human
immune cell genetic traits from their donor BLT mouse, such as the HLA-A2
haplotype that is of special interest for studying HLA-A2-restricted human T cell
immunotherapies. Moreover, an EGFP reporter gene engineered into the human immune
system was stably passed from BLT to proBLT mice, making proBLT mice suitable for
studying human immune cell gene therapy. This method provides an opportunity to
overcome a critical hurdle to utilizing the BLT humanized mouse model and enables
its more widespread use as a valuable preclinical research tool.
PMID- 27608731
TI - Modulating Magnetic Properties by Tailoring In-Plane Domain Structures in
Hexagonal YMnO3 Films.
AB - Periodic structures and the coupling of multiorder parameters in complex oxides
heterojunctions can generate exotic properties, of interest both for fundamental
researches and for device applications. Here, we report a self-assembling in
plane periodic domain structure, and the resulting rich magnetic states, in a h
YMnO3 thin film fabricated on c-face sapphire substrate. Detailed structural
investigations at atomic-level reveal the fashion of alternating domains under
tensile or compressive strains separated by a boundary region. Tuned by this in
plane domain structure, the abnormal magnetic properties, such as the
ferromagnetic enhancement and the unexpected spin glass state (below ~38 K), are
realized. Moreover, the existence of ferroelectric polarization is confirmed by
scanning transmission electron microscopy, which brings in the chances of
magnetoelectric coupling effect. These results manifest the close connections
between the magnetic properties and such in-plane microstructures, suggesting the
possibility of tuning the coupling effects via strain engineering in the
hexagonal manganite film.
PMID- 27608730
TI - The changing landscape of membrane protein structural biology through
developments in electron microscopy.
AB - Membrane proteins are ubiquitous in biology and are key targets for therapeutic
development. Despite this, our structural understanding has lagged behind that of
their soluble counterparts. This review provides an overview of this important
field, focusing in particular on the recent resurgence of electron microscopy
(EM) and the increasing role it has to play in the structural studies of membrane
proteins, and illustrating this through several case studies. In addition, we
examine some of the challenges remaining in structural determination, and what
steps are underway to enhance our knowledge of these enigmatic proteins.
PMID- 27608732
TI - Outcome of dichorionic diamniotic twin pregnancies with spontaneous PPROM before
24 weeks' gestation.
AB - OBJECTIVE: The objective of this study is to examine the outcome in dichorionic
diamniotic twin pregnancies with rupture of membranes (PPROM) before 24 weeks'
gestation. MATERIAL AND METHODS: Retrospective analysis of fetal and neonatal
outcomes in women with spontaneous PPROM before 24 weeks' gestation that were
treated at a single tertiary center. RESULTS: Twenty-nine pregnancies fulfilled
the inclusion criteria. Mean gestational age at the time of PPROM was 20.4 weeks.
Two women opted for termination. The remaining 27 (93.1%) women elected for
expectant management. Ten (37.0%) of these delivered before 24 + 0 weeks'
gestation. The median gestational age at the time of delivery in the remaining 17
(63%) cases was 26.4 weeks. In those patients that did not deliver within the
first 5 days of PPROM, the chance of reaching 24 + 0 weeks was 85%. Co-twins that
had PPROM compared with those without PPROM suffered more often from several
neonatal complications. Overall, about 40% of the fetuses in the PPROM group and
70% of the non-PPROM group survived without major complications. CONCLUSION:
Dichorionic diamniotic twin pregnancies with PPROM prior to 24 + 0 weeks'
gestation have a 60% chance of delivering at >24 weeks. Survival rates without
major complications in twins with and without PPROM are 40% and 70%,
respectively.
PMID- 27608733
TI - Association between high consumption of phytochemical-rich foods and
anthropometric measures: a systematic review.
AB - Phytochemical-rich foods consumption may be a valid nutritional strategy to
reduce the risk of weight gain and obesity. The phytochemical index (PI) is a
simple and nonspecific method to evaluate the phytochemical intake, defined as
the percentage of dietary calories derived from foods rich in phytochemicals. We
aimed to conduct a systematic review to evaluate whether high consumption of
phytochemical-rich foods evaluated by the PI is associated with lower values of
anthropometric measurements. The available literature suggests that the PI seems
to be inversely associated with body weight and waist circumference. Analyzing
the longitudinal changes in anthropometric variables, individuals with high
intake of phytochemicals gained less weight and fat mass when compared to those
with lower PI. Our findings suggest that higher PI is associated with lower body
mass index, waist circumference and adiposity. Whether the results are a reflex
of a lower calorie intake or the anti-obesity properties of phytochemicals
remains to be elucidated.
PMID- 27608734
TI - Supporting Paralympic wheelchair sport performance through technological,
physiological and environmental considerations.
PMID- 27608735
TI - Estimation of mercury amount in the components of spent U-type lamp.
AB - Spent U-type lamps are strongly encouraged to be separately managed in Korea,
because U-type lamps are categorized as a household waste and thereby could not
be managed properly. Determination of mercury amount in the components of U-type
lamp, such as plastics, glass tube and phosphor powder from 3 U-type lamp
manufacturers (A, B and C), is carried out to estimate the mercury content in
spent U-type lamps. Regardless of lamp manufacturers, the portion of mercury in
phosphor powder was higher than 90%, but that in plastics and others was less
than 1%. At an air flow rate of 1.0 L/min, the range of the initial mercury
concentration in vapor phase for U-type lamp was between 849 and 2076 ug/m3 from
3 companies. The estimated mercury amount in vapor phase of U-type lamp was in
the range from 0.206 mg for company A to 0.593 mg for company B. And the portion
of mercury in vapor phase in the total amount of mercury was estimated in the
range from 3.0% for company A to 6.7% for company B. Hence, it is desirable to
get rid of mercury from phosphor powder in order to perform U-type lamps
recycling.
PMID- 27608736
TI - Clinical investigation of biofilm in non-healing wounds by high resolution
microscopy techniques.
AB - OBJECTIVE: The aim of this study was to analyse wound biofilm from a clinical
perspective. Research has shown that biofilm is the preferred microbial phenotype
in health and disease and is present in a majority of chronic wounds. Biofilm has
been linked to chronic wound inflammation, impairment in granulation tissue and
epithelial migration, yet there lacks the ability to confirm the clinical
presence of biofilm. This study links the clinical setting with microscopic
laboratory confirmation of the presence of biofilm in carefully selected wound
debridement samples. METHOD: Human wound debridement samples were collected from
adult patients with chronic non-healing wounds who presented at the wound care
centre. Sample choice was guided by an algorithm that was developed based on what
is known about the characteristics of wound biofilm. The samples were then
evaluated by light microscopy and scanning electron microscopy for the presence
of biofilm. Details about subject history and treatment were recorded. Adherence
to biofilm-based wound care (BBWC) strategies was inconsistent. Other standard
antimicrobial dressings were used and no modern antiseptic wound dressings with
the addition of proven antibiofilm agents were available for use. RESULTS: Of the
patients recruited, 75% of the macroscopic samples contained biofilm despite the
prior use of modern antiseptic wound dressings and in some cases, systemic
antibiotics. Wounds found to contain biofilm were not all acutely infected but
biofilm was present when infection was noted. The clinical histories associated
with positive samples were consistent with ideas presented in the algorithm used
to guide sample selection. CONCLUSION: Visual cues can be used by the clinician
to guide suspicion of the presence of wound biofilm. This suspicion can be
further enhanced with the use of a clinical algorithm. Standard antiseptic wound
dressings used in this study demonstrated limited antibiofilm efficacy. This
study also highlighted a need for the clinical team to focus on expiration of
dressing action and consistent practice of BBWC strategies which includes the use
of proven antibiofilm agents.
PMID- 27608738
TI - Florence and forward.
PMID- 27608737
TI - Contact dermatitis in patients with chronic leg ulcers: a common and neglected
problem: a review 2000-2015.
AB - OBJECTIVE: Contact allergies can occur frequently in patients with chronic leg
ulcers (CLUs), even in those with a short duration of ulcerative disease. The
wide spectrum of therapeutic products promotes development of the delayed type of
hypersensitivity and continuous changes in the allergens pattern, which make the
diagnosis and treatment extremely difficult in many cases. A prompt diagnosis and
treatment of allergic contact dermatitis (ACD) in patients suffering from CLUs is
very important for a best clinical outcome of these two common diseases. Thus,
this review aims to highlight a common, challenging and often neglected problem.
METHOD: The search included all studies published between 2000 and September
2015. Keyword used were: 'allergic contact dermatitis leg ulcer', 'contact
dermatitis leg ulcers' 'contact dermatitis wound care' 'contact dermatitis non
healing wounds' 'contact sensitisation non-healing wounds'. RESULTS: Contact
allergy and polysensitisation are very frequent in patients suffering from CLUs.
Although it is believed modern dressings have a lower potential for inducing
cutaneous sensitisation, positive patch test reactions to modern dressing are
becoming common: hydrogels, followed by hydrocolloid and the ionic silver
containing wound dressing seem to be the principal causes of ACD. CONCLUSION:
This review wanted to highlighted ACD in CLUs as a common and neglected disease
whose economic and social burden has not previously been estimated, giving new
insights for clinical and therapeutic management.
PMID- 27608739
TI - An assessment of key risk factors for surgical site infection in patients
undergoing surgery for spinal metastases.
AB - OBJECTIVE: This study aimed to determine the rate of surgical site infection
(SSI) in patients undergoing surgery for spinal metastases, and identify key risk
factors for SSI among this patient group. METHOD: A retrospective case note
review was undertaken in adult patients being treated at a single specialist
centre for spinal surgery. RESULTS: There were 152 patients identified for
inclusion. Overall SSI rate was 11.2 per 100 patients (9.7 per 100 procedures).
An increase in the risk of SSI was observed when surgery involved a greater
number of vertebral levels (odds ratio 1.26, p=0.019) when controlling for
primary spinal region. Controlling for the number of spinal levels, the odds of
SSI increased by a factor of 5.6 (p=0.103) when the primary surgical region was
thoracic, as opposed to cervical or lumbar. CONCLUSION: In conclusion, surgery
associated with multiple vertebral levels for treatment of spinal metastases,
particularly of the thoracic spine, is associated with increased risk of SSI.
PMID- 27608740
TI - The Static Stiffness Index: an important parameter to characterise compression
therapy in vivo.
AB - The compression pressure, which corresponds to the dosage of compression therapy,
has been widely neglected up to now, not only concerning scientific literature,
but also in clinical practice. It is evident that compression pressures in the
upright position and during walking are clinically more relevant than just the
resting pressure. The Static Stiffness Index (SSI), which is the difference
between standing and resting pressure, is a valuable parameter characterising the
efficacy of a specific compression product to narrow/occlude the venous lumen.
This is a prerequisite for reducing venous reflux and exerting a massaging effect
necessary to improve the venous pumping function during movement. This article
provides an overview of the recent literature on the SSI, which supports the
recommendations of the International Compression Club. In addition, it aims to
provide an insight on the importance of the SSI in daily practice, as an
educational tool as well as in defining the properties of applied compression
therapy in clinical research.
PMID- 27608741
TI - Structure-based design of selective phosphodiesterase 4B inhibitors based on
ginger phenolic compounds.
AB - Phosphodiesterase 4 (PDE4) has been established as a drug target for inflammatory
diseases of respiratory tract like asthma and chronic obstructive pulmonary
disease. The selective inhibitors of PDE4B, a subtype of PDE4, are devoid of
adverse effects like nausea and vomiting commonly associated with non-selective
PDE4B inhibitors. This makes the development of PDE4B subtype selective
inhibitors a desirable research goal. Thus, in the present study, molecular
docking, molecular dynamic simulations and binding free energy were performed to
explore potential selective PDE4B inhibitors based on ginger phenolic compounds.
The results of docking studies indicate that some of the ginger phenolic
compounds demonstrate higher selective PDE4B inhibition than existing selective
PDE4B inhibitors. Additionally, 6-gingerol showed the highest PDE4B inhibitory
activity as well as selectivity. The comparison of binding mode of PDE4B/6
gingerol and PDE4D/6-gingerol complexes revealed that 6-gingerol formed
additional hydrogen bond and hydrophobic interactions with active site and
control region 3 (CR3) residues in PDE4B, which were primarily responsible for
its PDE4B selectivity. The results of binding free energy demonstrated that
electrostatic energy is the primary factor in elucidating the mechanism of PDE4B
inhibition by 6-gingerol. Dynamic cross-correlation studies also supported the
results of docking and molecular dynamics simulation. Finally, a small library of
molecules were designed based on the identified structural features, majority of
designed molecules showed higher PDE4B selectivity than 6-gingerol. These results
provide important structural features for designing new selective PDE4B
inhibitors as anti-inflammatory drugs and promising candidates for synthesis and
pre-clinical pharmacological investigations.
PMID- 27608742
TI - The Effectiveness of Topical Polyhexamethylene Biguanide (PHMB) Agents for the
Treatment of Chronic Wounds: A Systematic Review.
AB - INTRODUCTION: This is the first systematic review to explore the evidence on PHMB
and determine how effective this topical agent is for the treatment of chronic
wounds. MATERIALS AND METHODS: PubMed, Ovid MEDLINE, CINAHL, Embase, the Cochrane
library, and Scopus were searched for relevant articles published from 1946 to
February 3, 2014, with no restrictions on publication status. ProQuest was
searched for relevant dissertations, editorials, and conference abstracts. Non
indexed journals were searched and companies that manufacture wound care
materials containing PHMB were contacted for unpublished data. Only randomized
controlled trials available in English were included. Bias was assessed using the
CONSORT document for all included studies. After inclusion and exclusion criteria
were determined, four reviewers (ET, SK, SG, RD) independently reviewed each
title and abstract of the literature search results to determine whether the
paper should be included for this review. When disagreements on study inclusion
emerged, reviewers resolved them through discussion. RESULTS: Of the 1,725
articles identified in the search, 6 met inclusion criteria. Four studies
reported wound healing. Two of these studies evaluated changes in wound surface
area and the other two evaluated wound bed evolution with variable results. In
five studies, participants randomly assigned to PHMB topical agents showed
significant improvement in bacterial control compared to control groups. Five
studies reported pain reduction from the use of PHMB agents. DISCUSSION: There
were a small number of eligible studies found, but the interventions, outcome
measures, and outcome reporting varied greatly, making meta-analysis impossible.
PHMB agents were shown to promote healing and reduce pain more effectively than
control treatments. CONCLUSION: The existing evidence shows that topical PHMB may
promote healing of chronic stalled wounds, reduce bacterial burden, eliminate
methicillin-resistant staphylococcus aureus (MRSA), and alleviate wound-related
pain.
PMID- 27608744
TI - Total Shoulder Arthroplasty Demographics, Incidence, and Complications-A
Nationwide Inpatient Sample Database Study.
AB - INTRODUCTION: Total shoulder arthroplasty (TSA) has become a popular and
successful surgery to treat advanced glenohumeral arthritis, rotator cuff
arthropathy, and proximal humerus fractures. Historical data is available
investigating the epidemiology of total shoulder arthroplasty with regard to
patient characteristics, outcomes, and complications; however, there is a lack of
studies investigating the most recent and up to date national trends related to
shoulder replacement. The purpose of this study was to evaluate changes in the
annual incidence, various demographics, and complications of TSA in America.
MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) was assessed to
identify all patients who were admitted for TSA in the United States between 1998
and 2010. National trends in patient demographics, incidence, and length-of-stay
(LOS) were analyzed for correlations. The impacts of contributing factors to each
outcome were assessed using adjusted multivariable regression analysis. These
were used to calculate odds ratios of cohort demographics and their association
with complications and LOS. RESULTS: Admissions for TSA have risen (8,041 to
39,072 admissions). The majority of the cohort consisted of Caucasian men between
the ages of 64 and 79 years. The incidence rate of complications has remained
consistent. Female gender, age > 80 years, and higher Deyo Comorbidity scores
were risk factors for higher complications. The LOS has decreased (2.96 to 2.21
days) during the study time period. Female gender, African-American race,
Medicaid insurance, and higher Deyo Comorbidity scores were associated with
longer stays. DISCUSSION: Our study demonstrates a rapid increase in incidence
rates of TSAs within the 13-year period in the United States. An increased risk
of complications was noted with older age, female gender, and increased Deyo
score. CONCLUSION: Our findings may help health care providers identify ways to
better manage this procedure and select patients.
PMID- 27608743
TI - Peroneal Tubercle Hypertrophy: A Case Report.
AB - The peroneal tubercle is an osseous prominence present on the calcaneus bone at
the junction between the middle and the anterior third of its lateral surface. It
is a bony septum which divides the tendons of the peroneus brevis and the
peroneus longus and offers insertion to the inferior peroneal retinaculum. A
hypertrophy of this prominence causes pain in the lateral and the posterior part
of the foot while wearing shoes, rarely peroneal tenosynovitis can even cause it
to break. In the following pages, we will describe a case of peroneal tubercle
hypertrophy, visible even at clinical examination, in a 26-year-old male patient
without apparent causes nor previous trauma.
PMID- 27608745
TI - A Novel Motion-Preservation Technique for Intra and Intra-Intersegmental Repair
of Spondylolysis and Spondylolisthesis: The Lin Technique.
AB - OBJECTIVE: A novel motion-preserving technique to directly repair pars defects.
Moreover, the indications for repair are expanded to include those with disc
disease and associated spondylolisthesis. SUMMARY OF BACKGROUND DATA: The
challenge in treating pars defects has been that there are few techniques
available to stabilize them adequately. Treatment has focused on fusion across
the inter-space versus grafting and instrumentation of the defect itself. We
hypothesize that direct repair of the defect favors maintenance of normal motion
characteristics by preserving the functional unit of the disc. This paper
describes a motion-preserving technique to repair bilateral pars defects and its
early clinical outcomes. MATERIALS AND METHODS: A retrospective review of 20
patients with symptomatic bilateral pars defects treated with either intra
segmental or intra-intersegmental motion-preserving repair with two years of
follow-up. Fifteen patients met the criteria for single level fixation. Five
patients required additional fixation of flexible posterolateral fusion involving
the inferior segment. Rh-BMP and autologous bone graft were placed within the
defect. Plain film X-rays were used to determine stability, and thin-section CT
was used to assess healing of the defect. RESULTS: The procedure arrested any
further slippage in 100% of cases, with bony healing in 95% of cases as
demonstrated by CT scan. Clinical outcomes for the entire series were: excellent
n=14, good n=3, no significant help n=3. For all cases there was a 5% rate of non
union. CONCLUSION: Further study and development of the technique via
biomechanical testing is ongoing; however, the initial results are encouraging.
Bone formation appears to be linked to decreasing symptoms in patients with
bilateral pars fractures who have failed conservative treatment.
PMID- 27608746
TI - Innovative Multi-Modal Physical Therapy Reduces Incidence of Manipulation Under
Anesthesia (MUA) in Non-Obese Primary Total Knee Arthroplasty.
AB - INTRODUCTION: Patients may experience knee stiffness following total knee
arthroplasty (TKA). Non-operative measures, such as more physical therapy and
special splints are warranted in such cases. In the event of failure of these
measures to restore knee range of motion, more invasive procedures with higher
risks, such as manipulation under anesthesia (MUA) or repeat surgery, can be
utilized. Thus, it becomes essential to optimize their non-operative measures in
order to avoid more invasive, riskier options. Therefore, the purpose of this
study was to evaluate and compare: 1) range of motion, and 2) the rate of MUA in
patients who either underwent a multi-modal physical therapy regimen (IMMPT) or
standard-of-care post-operative therapy (standard) following primary total knee
arthroplasty. MATERIALS AND METHODS: We analyzed all non-obese patients who
underwent primary TKAs between January 2013 and December 2014 at our institution
who started an outpatient physical therapy program within six weeks of their
surgery (n = 127 knees). There were 86 women and 41 men who had a mean age of 67
years (range, 42 to 88 years). This cohort was stratified into those who
underwent an IMMPT regimen at our institution (n= 47) and those who underwent
standard therapy at an outside institution (N = 80). The range of motion and rate
of manipulation between the two groups was compared by using Chi-square and
Student's t-test, as appropriate. RESULTS: There were similar proportions of
those who had an optimal range of motion (>=110 degrees flexion and <=5 degrees
extension) in the IMMPT group as compared to the standard physical therapy cohort
(81% vs. 82%). The IMMPT cohort had a significantly lower proportion of patients
who underwent MUA as compared to the standard therapy cohort (2% vs. 13%).
CONCLUSIONS: This study shows an IMMPT protocol utilizing Astym(r) therapy
(Performance Dynamics, Inc. Muncie, Indiana) is able to significantly reduce the
rate of manipulation following a total knee arthroplasty. Furthermore, this IMMPT
approach was also able to achieve similar range of motion to the standard
physical therapy group while reducing the rate of manipulation, which may
indicate similar efficacy in restoring range of motion. Comparative randomized
studies are needed to determine the true benefit of this IMMPT protocol.
PMID- 27608747
TI - Delay in Diagnosis of Vertebral Osteomyelitis Affects the Utility of Cultures.
AB - INTRODUCTION: Obtaining blood or tissue cultures prior to administration of
antibiotics has been the standard of care in the treatment of osteomyelitis of
the spine. A delay in diagnosis of vertebral osteomyelitis is the primary culprit
for the inaccuracy of blood cultures and biopsies. The purpose of this study was
to evaluate the outcomes of spinal osteomyelitis in patients where the infecting
organism was identified through cultures in contrast to cases where the cultures
continued to be negative. MATERIALS AND METHODS: We retrospectively reviewed the
database of spinal osteomyelitis cases presented at a high-volume institution
from 2001-2011. This resulted in 91 patients (51 men and 40 women) who had a mean
age of 59 years with a mean follow-up of four years. Delay in diagnosis was
defined as greater than 2.5 months from first ER visit for non-specific back pain
to diagnosis of osteomyelitis without antibiotic treatment in the interim.
Nineteen patients had a delay in diagnosis (DD) and 72 were diagnosed early (ED).
Outcomes evaluated include clearance of infection, clinical outcomes measured by
Oswestry disability index scores (ODIs), and the efficacy of blood cultures and
biopsies. RESULTS: The ED group had a higher odds ratio of osteomyelitis
clearance compared to the delay in diagnosis group and this trended toward
significance [p=0.08]. The mean improvements in ODIs were significantly greater
in the ED group compared to the DD group. Positive blood cultures were more
positive when drawn within one month compared to after one month [p=.001].
Percutaneous biopsy cultures were more positive when drawn within 2.5 months
compared to after 2.5 months [p=.025]. Open biopsy cultures were more positive
when drawn within 4.5 months compared to after that [p<0.001]. DISCUSSION: We
found that delayed diagnosis may negatively affect the treatment outcome as
evidenced by the greater improvements in ODI scores among those diagnosed early.
Although we were unable to show a difference in clearance between early and
delayed diagnosis, it is quite possible that larger cohorts may have shown this
given the trend toward significance. CONCLUSION: Hence, an early diagnosis has
improved vertebral osteomyelitis clearance and clinical outcomes, and blood
cultures and biopsies may have a low yield if delayed.
PMID- 27608748
TI - When Do You Drain Epidural Abscesses of the Spine?
AB - BACKGROUND: How the relative volume of an epidural abscess on MRI affects
outcomes with antibiotics alone has limited literature. The purpose of this study
was to identify which infected epidural collections will reabsorb with
antibiotics alone. Specifically, what is the critical size and enhancement on
contrast MRIs to require a drainage procedure? MATERIALS AND METHODS: A
retrospective review of all spinal osteomyelitis patients from 2001-2012 was
performed. Inclusion criteria included appropriate initial imaging, lab results,
no drainage procedures of collections, and no treatment prior to admission at an
outside institution. Large size epidural abscess was defined as abscesses with a
volume greater than 1400 mm3. Clearance and mortality rates were evaluated.
RESULTS: The cohort consisted of 128 patients including 76 men and 52 women who
had a mean age of 62 years (range, 21 to 90 years) and had a mean follow-up of 38
months (range, 24 to 72 months). Patients with a large epidural abscess had a
greater clearance rate of the infection and decreased mortality rate when treated
with surgery or drainage compared to patients treated with antibiotics alone
[clearance: p=0.048; mortality: p=0.048]. Those small epidural abscesses had
similar clearance and mortality rates when treated with surgery or drainage
compared to antibiotics alone [clearance: p=0.75; mortality: p=0.13]. Patients
with non-enhancing epidural abscesses had similar clearance rates-but increased
mortality rates-when treated with antibiotics alone compared to surgery or
drainage [clearance: p>0.9; mortality: p=0.03]. Those with enhancing epidural
collections had similar clearance and mortality rates when treated with
antibiotics alone compared to surgery or drainage [clearance: p=0.08, mortality:
p=0.10]. CONCLUSION: Large epidural infected collections require surgery or a
percutaneous drainage procedure. Clearance rates are higher and mortality rates
are lower compared to non-operative management in these instances. Neurologically
intact patients with a small epidural collection can be treated with antibiotics
alone with good expected outcomes.
PMID- 27608749
TI - Transcutaneous Temperature Controlled Radiofrequency (TTCRF) for the Treatment of
Menopausal Vaginal/Genitourinary Symptoms.
AB - OBJECTIVE: The aim of this study was to evaluate the effects of non-ablative,
monopolar transcutaneous temperature controlled radiofrequency (TTCRF) technology
in the treatment of postmenopausal women suffering from genuine stress urinary
incontinence (SUI) related to menopause and to evaluate histological changes
vaginally associated with the treatment. MATERIALS AND METHODS: Subjective and
objective symptoms of SUI were assessed in study subjects before and after TTCRF,
(1 treatment every 30 days, for 3 months; n=10) and compared with the effects of
a placebo treatment on a control group of demographically similar women (n =10).
SUI was subjectively evaluated with subjective Urogenital Distress Inventory (UDI
6) and with the International Consultation on Incontinence Questionnaire-Urinary
Incontinence Short Form (ICIQ-UI SF) before and after TTCRF treatments and
objectively with cough stress test. Vaginal health was evaluated with the Vaginal
Health Index (VHI) score and visual analogue score (VAS) for dyspareunia and
dryness. Punch biopsies were obtained at the urethra-vesical junction in the
anterior compartment, before and at the end of the treatment protocol. Basic and
histochemical staining methods were used. RESULTS: In subjects suffering SUI,
TTCRF treatment was associated with a significant (p<0.01) improvement of ICIQ-SF
and UDI-6 scores. Seven of 10 patients (70%) had a negative cough stress test
after the treatment protocol. Improvements were maintained up to the 12th week of
follow-up. The results were supported by the positive histologic changes seen
vaginally in women suffering from postmenopausal vaginal atrophy. TTCRF was well
tolerated with no complications reported in study patients. CONCLUSION: TTCRF
treatment in postmenopausal women suffering from SUI showed significant
improvement in both objective and subjective symptoms. Vaginal health scores also
improved as did VAS for dryness and dyspareunia. We feel these improvements were
related to histological changes related to improvement in vaginal atrophy that
were not observed in placebo patients.
PMID- 27608750
TI - Post-Ablation Endometrial Carcinoma (PAEC) Following Radiofrequency Endometrial
Ablation: A Case Report and Its Implications for Management of Endometrial
Ablation Failures.
AB - Endometrial ablation (EA) has become one of the most commonly performed
gynecologic procedures in the United States and other developed countries. Global
endometrial ablation (GEA) devices have supplanted resectoscopic ablation
primarily because they have brought with them technical simplicity and
unprecedented safety. These devices, all of which received FDA approval between
1997 and 2001, are typically used to treat abnormal uterine bleeding (AUB) in
premenopausal women. Several million women in the US who have undergone a
previous EA procedure are about to enter the risk pool for the development of
endometrial cancer (EC). Ours is the 18th reported case of post-ablation
endometrial carcinoma (PAEC) in the English literature. This case underscores the
diagnostic challenges faced in evaluating women with a history of a previous EA
who cannot be properly evaluated with conventional techniques such as endometrial
biopsy and sonohysterography.
PMID- 27608751
TI - Novel Sensor Tibial Inserts in Total Knee Arthroplasty: A Review.
AB - Traditional techniques to balance total knee arthroplasties are often subject to
variability, as they are usually based on the surgeon's subjective assessment.
Improperly balanced total knee arthroplasties can cause complications such as
stiffness, pain, or instability, which may ultimately result in a revision
procedure. In an effort to mitigate this, a tibial insert sensor technology has
recently been developed to allow for quantifiable, objective measurements of soft
tissue balancing. A systematic review of the current literature was performed,
highlighting the utility of this sensor tibial insert with focus on: (1)
compartment loading pressures; (2) component orientations; and (3) clinical
outcomes.
PMID- 27608752
TI - The magnetic and electronic properties of oxyselenides-influence of transition
metal ions and lanthanides.
AB - Magnetic oxyselenides have been a topic of research for several decades, firstly
in the context of photoconductivity and thermoelectricity owing to their
intrinsic semiconducting properties and ability to tune the energy gap through
metal ion substitution. More recently, interest in the oxyselenides has
experienced a resurgence owing to the possible relation to strongly correlated
phenomena given the fact that many oxyselenides share a similar structure to
unconventional superconducting pnictides and chalcogenides. The two dimensional
nature of many oxyselenide systems also draws an analogy to cuprate physics where
a strong interplay between unconventional electronic phases and localised
magnetism has been studied for several decades. It is therefore timely to review
the physics of the oxyselenides in the context of the broader field of strongly
correlated magnetism and electronic phenomena. Here we review the current status
and progress in this area of research with the focus on the influence of
lanthanides and transition metal ions on the intertwined magnetic and electronic
properties of oxyselenides. The emphasis of the review is on the magnetic
properties and comparisons are made with iron based pnictide and chalcogenide
systems.
PMID- 27608753
TI - Surface engineering of SPIONs: role of phosphonate ligand multivalency in
tailoring their efficacy.
AB - We report the design of scaffolds containing mono-, bis-, and tris-phosphonate
coordinating groups, and a polyethylene glycol chain, for stabilizing
superparamagnetic iron oxide nanoparticles (SPIONs), using simple and versatile
chemistry. We demonstrate that the number of anchoring phosphonate sites on the
ligand influence the colloidal stability, magnetic and biological properties of
SPIONs, and the latter do not solely depend on attaching moieties that can
enhance their aqueous dispersion. These parameters can be tailored by the number
of conjugation sites on the ligand, as evidenced from dynamic light scattering at
various salt concentrations, magnetic relaxivities and cell viability studies.
PMID- 27608754
TI - "MAPseq"-uencing Long-Range Neuronal Projections.
AB - Kebschull et al. (2016a) describe "MAPseq," which tags individual neurons from a
specific brain region with individual mRNA barcodes and sequences these barcodes
in other brain regions. This allows the simultaneous mapping of long-range
neuronal projections at single-cell resolution.
PMID- 27608755
TI - Intercellular Networks Underlying Developmental Decisions.
AB - In this issue of Neuron, Yuzwa et al. (2016) identify secreted factors that
influence the cell fates of embryonic neural progenitor cells. Surprisingly, the
major contributors are trophic factors from the GDNF family and a cytokine,
interferon-gamma. Advanced analysis of proteomic and transcriptome data
discovered ligand receptors that influence cell-cell communication.
PMID- 27608756
TI - Illuminating the Gap: Neuronal Cross-Talk within Sensory Ganglia and Persistent
Pain.
AB - How primary sensory neurons contribute to persistent pain remains unclear. A
novel imaging technique introduced here by Kim et al. (2016) in this issue of
Neuron to view the activities of large numbers of ganglion neurons simultaneously
analyzes the importance of neuronal cross-talk in pain transmission.
PMID- 27608757
TI - Visual Processing: Hungry Like the Mouse.
AB - In this issue of Neuron, Burgess et al. (2016) explore how motivational state
interacts with visual processing, by examining hunger modulation of food
associated visual responses in postrhinal cortical neurons and their inputs from
amygdala.
PMID- 27608758
TI - Investigating the Limits of Neurovascular Coupling.
AB - O'Herron et al. (2016) perform two-photon imaging of vascular and neural
responses in cat and rodent primary visual cortex to investigate the limits of
neurovascular coupling. Their results suggest important constraints on making
inferences about neuronal responses from hemodynamic activity.
PMID- 27608761
TI - A Synaptotagmin Isoform Switch during the Development of an Identified CNS
Synapse.
PMID- 27608762
TI - Sleep and Movement Differentiates Actions of Two Types of Somatostatin-Expressing
GABAergic Interneuron in Rat Hippocampus.
PMID- 27608760
TI - Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the
Autism-Linked Excitatory Synaptic Suppressor MDGA2.
AB - Mutations in a synaptic organizing pathway contribute to autism. Autism
associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol
anchor 2) are thought to reduce excitatory/inhibitory transmission. However, we
show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2
blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse
development. Mdga2(+/-) mice, modeling autism mutations, demonstrated increased
asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with
no change in measures of inhibitory synapses. Behavioral assays revealed an
autism-like phenotype including stereotypy, aberrant social interactions, and
impaired memory. In vivo voltage-sensitive dye imaging, facilitating comparison
with fMRI studies in autism, revealed widespread increases in cortical
spontaneous activity and intracortical functional connectivity. These results
suggest that mutations in MDGA2 contribute to altered cortical processing through
the dual disadvantages of elevated excitation and hyperconnectivity, and indicate
that perturbations of the NRXN-NLGN pathway in either direction from the norm
increase risk for autism.
PMID- 27608763
TI - Platelet derived FasL contributes to apoptosis in stroke.
PMID- 27608759
TI - Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of
Multiple Sclerosis and Alzheimer's Disease?
AB - Lymphatic vasculature drains interstitial fluids, which contain the tissue's
waste products, and ensures immune surveillance of the tissues, allowing immune
cell recirculation. Until recently, the CNS was considered to be devoid of a
conventional lymphatic vasculature. The recent discovery in the meninges of a
lymphatic network that drains the CNS calls into question classic models for the
drainage of macromolecules and immune cells from the CNS. In the context of
neurological disorders, the presence of a lymphatic system draining the CNS
potentially offers a new player and a new avenue for therapy. In this review, we
will attempt to integrate the known primary functions of the tissue lymphatic
vasculature that exists in peripheral organs with the proposed function of
meningeal lymphatic vessels in neurological disorders, specifically multiple
sclerosis and Alzheimer's disease. We propose that these (and potentially other)
neurological afflictions can be viewed as diseases with a neuro-lympho-vascular
component and should be therapeutically targeted as such.
PMID- 27608764
TI - Alcohol use and depression: link with adherence and viral suppression in adult
patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross
sectional study.
AB - BACKGROUND: Depression and alcohol use disorder have been shown to be associated
with poor adherence to antiretroviral therapy (ART). Studies examining their
association with viral suppression in rural Africa are, however, scarce. METHODS:
This study reports prevalence of depressive symptoms and alcohol use disorder,
and their potential association with adherence and viral suppression in adult
patients on ART in ten clinics in rural Lesotho, Southern Africa. RESULTS: Among
1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were
hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of
depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both
alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol
use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor
adherence. There was, however, no significant association with viral suppression.
CONCLUSIONS: Whereas the results of this study confirm previously reported
association of alcohol use disorder with adherence to ART, there was no
association with viral suppression. TRIAL REGISTRATION: April 28th 2014;
NCT02126696 .
PMID- 27608765
TI - Bilateral strio-pallido-dentate calcinosis (Fahr's disease): report of seven
cases and revision of literature.
AB - BACKGROUND: Fahr's disease is rare a neurodegenerative idiopathic condition
characterized by symmetric and bilateral calcifications of basal ganglia, usually
associated with progressive neuropsychiatric dysfunctions and movement disorders.
The term "Fahr's syndrome" is used in presence of calcifications secondary to a
specific cause, but the variability of etiology, pathogenesis, and clinical
picture underlying this condition have raised the question of the real existence
of a syndrome. Several classifications based on the etiology, the location of
brain calcifications and the clinical presentation have been proposed. Here we
describe seven clinical cases of basal ganglia calcifications, in order to search
for pathognomonic features and correlations between clinical picture and imaging
findings. CASES PRESENTATION: The patients came to our attention for different
reasons (most of them for memory/behavior disturbances); all underwent neuro
psychologic evaluation and neuro-imaging. All patients showed variable degrees of
deterioration in cognitive function; anxiety and depression were frequent too,
and resistant to treatment in all cases. Less frequent, but severe if present,
were psychotic symptoms, with different grade of structure and emotional
involvement, and always resistant to treatment. We observed only few cases of
extrapyramidal disorders related to the disease itself; anyway, mild
extrapyramidal syndrome occurred quite frequently after treatment with
antipsychotics. CONCLUSION: Based on these findings we discourage the use of the
term "Fahr's syndrome", and suggest to refer to Idiopathic or Secondary basal
ganglia calcification. Unlike early onset forms (idiopathic or inherited), the
clinical presentation of late onset form and Secondary basal ganglia
calcification seems to be really heterogeneous. Case-control studies are
necessary to determine the actual significance of basal ganglia calcification in
the adult population and in the elderly, in cognitive, physical and emotional
terms.
PMID- 27608766
TI - A review of health promotion funding for older adults in Europe: a cross-country
comparison.
AB - BACKGROUND: Health promotion interventions for older adults are important as they
can decrease the onset and evolution of diseases and thus can reduce the medical
costs related to those diseases. However, there is no comparative evidence on how
those interventions are funded in European countries. The aim of this study is to
explore the funding of health promotion interventions in general and health
promotion interventions for older adults in particular in European countries.
METHOD: We use desk research to identify relevant sources of information such as
official national documents, international databases and scientific articles.
Fora descriptive overview on how health promotion is funded, we focus on three
dimensions: who is funding health promotion, what are the contribution mechanisms
and who are the collecting agents. In addition to general information on funding
of health promotion, we explore how programs on health promotion for older
population groups are funded. RESULTS: There is a great diversity in funding of
health promotion in European countries. Although public sources (tax and social
health insurance revenues) are still most often used, other mechanisms of funding
such as private donations or European funds are also common. Furthermore, there
is no clear pattern in the funding of health promotion for different population
groups. This is of particular importance for health promotion for older adults
where information is limited across European countries. CONCLUSIONS: This study
provides an overview of funding of health promotion interventions in European
countries. The main obstacles for funding health promotion interventions are lack
of information and the fragmentation in the funding of health promotion
interventions for older adults.
PMID- 27608767
TI - Carotid endarterectomy versus carotid angioplasty for stroke prevention: a
systematic review and meta-analysis.
AB - BACKGROUND: This meta-analysis aimed to evaluate the efficacy of carotid
endarterectomy (CE) compared with carotid angioplasty (CA) in preventing stroke.
Whether the use of CE is more efficient in preventing stroke than CA is a matter
of debate. METHODS: Data were gathered from randomized controlled trials to
evaluate the effect of CE compared with CA on the risk of stroke. Electronic
searches in PubMed, Embase, and the Cochrane Library were performed to identify
studies till November 2014. Only randomized controlled trials performed on
patients who received either CE or CA for stroke prevention were included.
RESULTS: Nine relevant trials (n = 7163) that met the inclusion criteria were
identified. In a pooled analysis, CE resulted in 35 % reduction in relative risk
(RR) for short-term stroke [RR, 0.65; 95 % confidence interval (CI): 0.47-0.89; P
= 0.007)] and 22 % reduction in RR for long-term stroke (RR, 0.78; 95 % CI: 0.66
0.93; P = 0.006) relative to CA. However, CE also increased the risk of 30-day
myocardial infarction by 114 % compared with CA (RR, 2.14; 95 % CI: 1.30-3.53; P
= 0.003). Sensitivity analyses suggested that CE might influence the risk of 30
day major vascular events and 1-year major vascular events compared with CA.
CONCLUSIONS: CE could reduce the risk of stroke (whether short term or long
term), but resulted in a relative increase in the risk of myocardial infarction.
This study might guide appropriate judgments about treatment approach. It also
provided evidence to justify general guidelines for patients with carotid artery
stenosis.
PMID- 27608768
TI - Quality of care for remote orthopaedic consultations using telemedicine: a
randomised controlled trial.
AB - BACKGROUND: Decentralised services using outreach clinics or modern technology
are methods to reduce both patient transports and costs to the healthcare system.
Telemedicine consultations via videoconference are one such modality. Before new
technologies are implemented, it is important to investigate both the quality of
care given and the economic impact from the use of this new technology. The aim
of this clinical trial was to study the quality of planned remote orthopaedic
consultations by help of videoconference. METHOD: We performed a randomised
controlled trial (RCT) with two parallel groups: video-assisted remote
consultations at a regional medical centre (RMC) as an intervention versus
standard consultation in the orthopaedic outpatient clinic at the University
Hospital of North Norway (UNN) as a control. The participants were patients
referred to or scheduled for a consultation at the orthopaedic outpatient clinic.
The orthopaedic surgeons evaluated each consultation they performed by completing
a questionnaire. The primary outcome measurement was the difference in the sum
score calculated from this questionnaire, which was evaluated by the non
inferiority of the intervention group. The study design was based on the
intention to treat principle. Ancillary analyses regarding complications, the
number of consultations per patient, operations, patients who were referred again
and the duration of consultations were performed. RESULTS: Four-hundred patients
were web-based randomised. Of these, 199 (98 %) underwent remote consultation and
190 (95 %) underwent standard consultation. The primary outcome, the sum score of
the specialist evaluation, was significantly lower (i.e. 'better') at UNN
compared to RMC (1.72 versus 1.82, p = 0.0030). The 90 % confidence interval (CI)
for the difference in score (0.05, 0.17) was within the non-inferiority margin.
The orthopaedic surgeons involved evaluated 98 % of the video-assisted
consultations as 'good' or 'very good'. In the ancillary analyses, there was no
significant difference between the two groups. CONCLUSIONS: This study supports
the argument that it is safe to offer video-assisted consultations for selected
orthopaedic patients. We did not find any serious events related to the mode of
consultation. Further assessments of the economic aspects and patient
satisfaction are needed before we can recommend its wider application. TRIAL
REGISTRATION: ClinicalTrials.gov identifier: NCT00616837.
PMID- 27608769
TI - Where's WALY? : A proof of concept study of the 'wellbeing adjusted life year'
using secondary analysis of cross-sectional survey data.
AB - BACKGROUND: The Quality-Adjusted Life Year (QALY) is a measure that combines life
extension and health improvement in a single score, reflecting preferences around
different types of health gain. It can therefore be used to inform decision
making around allocation of health care resources to mutually exclusive options
that would produce qualitatively different health benefits. A number of quality
of-life instruments can be used to calculate QALYs. The EQ-5D is one of the most
commonly used, and is the preferred option for submissions to NICE (
https://www.nice.org.uk/process/pmg9/ ). However, it has limitations that might
make it unsuitable for use in areas such as public and mental health where
interventions may aim to improve well-being. One alternative to the QALY is a
Wellbeing-Adjusted Life Year. In this study we explore the need for a Wellbeing
Adjusted Life Year measure by examining the extent to which a measure of
wellbeing (the Warwick-Edinburgh Mental Well-being Scale) maps onto the EQ-5D-3L.
METHODS: Secondary analyses were conducted on data from the Coventry Household
Survey in which 7469 participants completed the EQ-5D-3L, Warwick-Edinburgh
Mental Well-being Scale, and a measure of self-rated health. Data were analysed
using descriptive statistics, Pearson's and Spearman's correlations, linear
regression, and receiver operating characteristic curves. RESULTS: Approximately
75 % of participants scored the maximum on the EQ-5D-3L. Those with maximum EQ-5D
3L scores reported a wide range of levels of mental wellbeing. Both the Warwick
Edinburgh Mental Well-being Scale and the EQ-5D-3L were able to detect
differences between those with higher and lower levels of self-reported health.
Linear regression indicated that scores on the Warwick-Edinburgh Mental Well
being Scale and the EQ-5D-3L were weakly, positively correlated (with R(2) being
0.104 for the index and 0.141 for the visual analogue scale). CONCLUSION: The
Warwick-Edinburgh Mental Well-being Scale maps onto the EQ-5D-3L to only a
limited extent. Levels of mental wellbeing varied greatly amongst participants
who had the maximum score on the EQ-5D-3L. To evaluate the relative effectiveness
of interventions that impact on mental wellbeing, a new measure - a Wellbeing
Adjusted Life Year - is needed.
PMID- 27608770
TI - The role of alcohol in the management of hypertension in patients in European
primary health care practices - a survey in the largest European Union countries.
AB - BACKGROUND: Even though addressing lifestyle problems is a major recommendation
in most guidelines for the treatment of hypertension (HTN), alcohol problems are
not routinely addressed in the management of hypertension in primary health care.
METHODS: Internet based survey of 3081 primary care physicians, recruited via the
mailing lists of associations for general practitioners (GPs) in France, Germany,
Italy, Spain and the UK. Clinical practice, attitudes, knowledge, education and
training were assessed. Logistic regression to predict screening, brief
intervention and treatment for alcohol dependence in the management of
hypertension were assessed. RESULTS: Overall, about one third of the interviewed
GPs reported sufficient screening in cases with HTN (34.0 %, 95 % confidence
interval (CI):32.1-35.8 %). One out of five GPs screened and delivered brief
interventions in HTN patients with hazardous consumption (22.2 %, 95 % CI: 20.6
23.8 %) and about one in 13 GPs provided treatment for HTN patients with alcohol
dependence other than advice or brief intervention (7.8 %, 95 % CI: 6.8-8.9 %).
Post-graduate training and belief in their effectiveness predicted interventions.
There were marked differences between countries. CONCLUSIONS: While current
interventions were overall low, marked differences between countries indicate
that current practices could be improved. Education and post-graduate training
seems to be key in improving clinical practice of including interventions for
problematic alcohol consumption and alcohol dependence in primary health care.
PMID- 27608772
TI - Phase II open-label study of recombinant circularly permuted TRAIL as a single
agent treatment for relapsed or refractory multiple myeloma.
AB - BACKGROUND: Despite the recent development of new therapies, multiple myeloma
(MM) remains an incurable disease. Thus, new, effective treatments are urgently
needed, particularly for relapsed or refractory MM (RRMM). In an earlier phase I
study, a novel form of recombinant human Apo2L/tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL) that is currently in clinical development for
the treatment of hematologic malignancies, i.e., circularly permuted TRAIL (CPT),
was well tolerated at a dose of 2.5 mg/kg per day and showed promising
preliminary activity in patients with RRMM. This phase II, open-label,
multicenter study further investigated the efficacy and safety of 2.5-mg/kg per
day CPT as single-agent therapy for patients with RRMM. METHODS: Patients with
RRMM were treated once daily with CPT (2.5 mg/kg, intravenously) for 14
consecutive days for each 21-day cycle. Clinical response and toxicity were
assessed after each treatment cycle. RESULTS: Twenty-seven patients received CPT.
Using the European Group for Blood and Marrow Transplantation criteria, we
calculated the overall response rate of 33.3% with 1 near-complete response (nCR)
and 8 partial responses (PRs). The clinical benefit rate (48.1%) included 1 nCR,
8 PRs, and 4 minimal responses. The most common treatment-related adverse events
(TRAEs) were fever, aspartate aminotransferase elevation, alanine
aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia.
We graded toxicity using the Common Toxicity Criteria for Adverse Events, version
3.0, and determined that 37.0% of patients had at least 1 grade 3-4 TRAE.
CONCLUSIONS: CPT as a single agent can elicit a response in patients with RRMM
and is well tolerated. Further clinical investigation is warranted. Trial
Registration ChiCTR-ONC-12002065 http://www.chictr.org/cn.
PMID- 27608771
TI - Amphotericin B Inhibits Enterovirus 71 Replication by Impeding Viral Entry.
AB - Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to
cardiopulmonary complications and death in young children. There is thus an
urgent need to find new treatments to control EV71 infection. In this study, we
report potent inhibition of EV71 by a polyene antibiotic Amphotericin B.
Amphotericin B profoundly diminished the expression of EV71 RNA and viral
proteins in the RD cells and the HEK293 cells. As a result, EV71 production was
inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75
MUM in RD cells and 0.32 MUM in 293 cells. In addition to EV71, EV68 was also
strongly inhibited by Amphotericin B. Results of mechanistic studies revealed
that Amphotericin B targeted the early stage of EV71 infection through impairing
the attachment and internalization of EV71 by host cells. As an effective anti
fungi drug, Amphotericin B thus holds the promise of formulating a novel
therapeutic to treat EV71 infection.
PMID- 27608773
TI - Small activating RNA upregulates NIS expression: promising potential for
hepatocellular carcinoma endoradiotherapy.
AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
worldwide. Currently, the clinical strategies available for the treatment of HCC
remain insufficient for the poor prognosis. Sodium/iodide symporter (NIS)-based
radioiodine therapy is proposed as a promising therapeutic strategy for the
treatment of HCC. However, it is difficult for HCC cells to trap iodine for the
lower expression of NIS. Small activating RNA (saRNA) is a newly identified small
double-stranded RNA (dsRNA) that can induce endogenous gene expression by
targeting promoter sequences. Here, we designed an saRNA (saRNA-482) that
targeted the NIS promoter sequences. In the cultured HepG2 cells and Hep3B cells,
the expressions of NIS were upregulated after transfection of saRNA-482. In
addition, the uptake of 125I increased in the cultured HepG2 and Hep3B cells
transfected with saRNA-482. Furthermore, the cell viabilities were significantly
inhibited in the saRNA-482-transfected HepG2 and Hep3B cells after 131I
treatment. Meanwhile, the apoptosis of saRNA-482-transfected HepG2 and Hep3B
cells significantly increased after 131I treatment. The results suggest that RNA
activation-mediated upregulation of NIS may have an endoradiotherapeutic
potential in the treatment of HCC.
PMID- 27608774
TI - The inhibition of epidermal growth factor receptor signaling by hexagonal
selenium nanoparticles modified by SiRNA.
AB - The aim of this study was to investigate the effect of hexagonal selenium
nanoparticles modified by SiRNA (HSNM-SiRNA) to inhibit epidermal growth factor
receptor (EGFR) signaling in Human non-small-cell lung cancer (NSCLC). After
synthesis, HSNM-SiRNA and HSNs were separately exposed to NSCLC cell lines (A549,
H1299, H520, and H1975), and incubated for 6 h at 37 degrees C. Next, the
expression of NFKB, MYC, STAT, ELK1, and GAPDH was evaluated by western blot and
real-time PCR. The percentage of apoptotic cells and cell cycle progression were
measured when exposed to HSNM-SiRNA and HSNs. Both western blot and real-time PCR
results showed that HSNM-SiRNA could down-regulate the expression of all EGFR
signaling genes. The percentage of apoptotic cells was significantly increased in
all cell lines when exposed to HSNM-SiRNA (P>0.05). HSNM-SiRNA in A549 and H1299
cells significantly increased the proportion of cells in G1/G0 phase and
significantly decreased the proportion of cells in S phase.
PMID- 27608776
TI - Nickel-Catalyzed Site-Selective C-H Bond Difluoroalkylation of 8-Aminoquinolines
on the C5-Position.
AB - A simple and efficient protocol for nickel-catalyzed regioselective C-H bond
difluoroalkylation of 8-aminoquinoline scaffolds with functionalized
difluoromethyl bromides was developed. The reaction has broad substrate scope and
provides a facile and useful access to the corresponding C5-functionalized
difluoromethylated quinolines in good to excellent yields.
PMID- 27608775
TI - Raman-based detection of hydroxyethyl starch in kidney allograft biopsies as a
potential marker of allograft quality in kidney transplant recipients.
AB - In brain-dead donor resuscitation, hydroxyethyl starch (HES) use has been
associated with presence of osmotic-nephrosis-like lesions in kidney transplant
recipients. Our aim was to determine whether the presence of HES in protocol
renal graft biopsies at three months (M3) after transplantation is associated
with renal graft quality. According to the HES administered to the donor during
the procurement procedure, two groups of patients were defined according graft
exposition to HES: HES group, (N = 20) and control group (N = 6). Detection and
relative quantification of HES was performed by Raman spectroscopy microimaging
on M3 protocol renal graft biopsies. Statistical analyses were used to
investigate the association between Raman data and graft characteristics. HES
spectral signal was revealed negative in the control group, whereas it was
positive in 40% of biopsies from the HES group. In the HES group, a stronger HES
signal was associated with a lower risk of graft failure measured by the Kidney
Donor Risk Index (KDRI) and was correlated with the allograft kidney function.
Thus, HES accumulation in donor kidney, as probed by Raman biophotonic technique,
is correlated with the quality of donor kidney and consequently the graft renal
function and graft survival.
PMID- 27608793
TI - [Not Available].
AB - Psoriatic arthritis (PsA) is a chronic inflammatory disease that possibly leads
to structural damage and to a reduction of joint function and poor quality of
life. Treatment of PsA has changed since its introduction of anti- TNF drugs,
which have shown to reduce the symptoms and signs of the disease and slow the
radiographic progression. However, recently, the discovery of new pathogenic
mechanisms have made possible the development of new molecules that target pro
inflammatory cytokines involved in skin, joint and entheseal inflammation. New
drugs like ustekinumab, secukinumab and apremilast inhibit interleukin axis and
intracellular pathways and showed their efficacy and safety in randomized
clinical trials. These drugs have been recently approved for the treatment of PsA
and included in the new EULAR and GRAPPA treatment recommendations. The aim of
this paper is to briefly review the clinical trials that led to their approval
for PsA.
PMID- 27608794
TI - The negative bone effects of the disease and of chronic corticosteroid treatment
in premenopausal women affected by rheumatoid arthritis.
AB - Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis
(RA). The chronic corticosteroid treatment, the functional impairment associated
with RA and the disease itself appear to be the most relevant determinants. Most
of the previous studies involved postmenopausal women, in whom the estrogenic
deficiency might amplify the negative effect towards bone of both RA and
corticosteroid therapy. We decided to evaluate bone health in a cohort of
premenopausal RA patients. The study population includes 47 premenopausal women
attending our outpatient clinic for RA and twice as many healthy age-matched
control women selected from the hospital personnel. The bone density at the spine
and femoral neck were significantly lower in patients with RA as compared with
controls. When spine bone mineral density (BMD) values were adjusted for the
cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus
body mass index (BMI) the mean differences between two groups decreased but they
remained statistically significant. We found no difference when the spine BMD was
adjusted for cumulative GC dose, BMI and health assessment questionnaire. The
difference in femoral neck BMD remained statistically significant also after all
the same adjustments. In conclusion, our study shows that a BMD deficiency is
frequent also in premenopausal women affected by RA, especially at femoral site
and that the main determinants of this bone loss are not only the disease-related
weight loss, corticosteroid therapy and functional impairment, but also the
systemic effects of the disease itself.
PMID- 27608795
TI - Spine and sacroiliac joints on magnetic resonance imaging in patients with early
axial spondyloarthritis: prevalence of lesions and association with clinical and
disease activity indices from the Italian group of the SPACE study.
AB - Our aim was to determine the prevalence of spine and sacroiliac joint (SIJ)
lesions on magnetic resonance imaging (MRI) in patients with early axial
spondyloarthritis (axSpA) and their correlation with disease activity indices.
Sixty patients with low back pain (LBP) (>=3 months, <=2 years, onset <=45
years), attending the SpA-clinic of the Unita Operativa Complessa Reumatologia of
Padova [SpondyloArthritis-Caught-Early (SPACE) study], were studied following a
protocol including physical examination, questionnaires, laboratory tests, X-rays
and spine and SIJ MRI. Positive spine and SIJ MRI and X-rays images were scored
independently by 2 readers using the SPARCC method, modified Stoke ankylosing
spondylitis spine score and New York criteria. The axial pain and localization of
MRI-lesions were referred to 4 sites: cervical/thoracic/lumbar spine and SIJ. All
patients were classified into three groups: patients with signs of radiographic
sacroiliitis (r-axSpA), patients without signs of r-axSpA but with signs of
sacroiliitis on MRI (nr-axSpA MRI SIJ+), patients without signs of sacroiliitis
on MRI and X-rays (nr-axSpA MRI SIJ-). The median age at LBP onset was 29.05+/
8.38 years; 51.6% of patients showed bone marrow edema (BME) in spine-MRI and
56.7% of patients in SIJ-MRI. Signs of enthesitis were found in 55% of patients
in the thoracic district. Of the 55% of patients with BME on spine-MRI, 15%
presented presented a negative SIJMRI. There was a significant difference between
these cohorts with regard to the prevalence of radiographic sacroiliitis, active
sacroiliitis on MRI and SPARCC SIJ score. The site of pain correlated
statistically with BME lesions in thoracic and buttock districts. Since positive
spine-MRI images were observed in absence of sacroiliitis, we can hypothesize
that this finding could have a diagnostic significance in axSpA suspected axSpA.
PMID- 27608796
TI - Evaluation of Th9 lymphocytes in peripheral blood of rheumatoid arthritis
patients and correlation with anti-tumor necrosis factor therapy: results from an
in vitro pivotal study.
AB - The aim of this study was to determine the prevalence of T helper 9 (Th9)
lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible
association between the percentage of Th9 and the discontinuation of a biological
treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected
peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and
10 healthy controls. Among RA patients, 15 were not receiving any
immunosuppressive drug, 20 were successfully treated with infliximab and 20
discontinued infliximab because of adverse events or inefficacy and were treated
with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L
for 18 h, and the percentage of Th9 cells was assessed by means of flow
cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4
, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric
analysis revealed no significant decrease in the percentage of Th9 cells after
infliximab exposure in any of the groups, although it was lower in healthy
controls than RA patients either before and after the infliximab stimulation
assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is
still poorly known. IL-9 levels are increased in RA patients, in whom this
cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and
their prevalence is higher in RA patients than in healthy subjects; however our
experiment in vitro does not demonstrate an association between Th9 lymphocytes
and the response to infliximab. Further studies are required to evaluate the real
involvement of Th9 population in the immunogenicity of anti-TNF agents.
PMID- 27608798
TI - Idiopathic granulomatous mastitis with erythema nodosum and polyarthritis.
AB - A 25 year-old woman presented with a painful mass in the left breast,
polyarthritis and erythema nodosum. Fine needle aspiration cytology led to a
diagnosis of granulomatous mastitis. Oral prednisolone rapidly improved the
arthritis and the erythema nodosum. Granulomatous mastitis is a very rare,
chronic inflammatory disease and only ten patients with granulomatous mastitis
with erythema nodosum and polyarthitis have been described.
PMID- 27608797
TI - Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with
methotrexate in rheumatoid arthritis patients: a comparison study.
AB - The objective of this study was to compare the tolerability of methotrexate in
two different regimes of folic acid (FA) supplementation in rheumatoid arthritis
(RA). We performed a multicenter, cross-sectional observational cohort study on
240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA
weekly supplementation. There were no significant differences for side effects
(14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus
13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower
disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44
(1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30
mg per week was associated with similar tolerability of methotrexate in RA
patients.
PMID- 27608799
TI - Isolated oculocutaneous sarcoidosis in a teenage male: a rare case report.
AB - Sarcoidosis is an inflammatory disease with multisystem involvement characterized
by the presence of noncaseating granulomas. It can affect virtually every organ
of the body, with lung involvement being most common occurring in >90% of
patients. Other organs affected are skin, eye and liver. Skin involvement is
common, affecting 25-35%. Here we present a rare case of a 15 year-old male with
isolated oculocutaneous sarcoidosis without systemic involvement.
PMID- 27608800
TI - Possible relationship between certolizumab pegol and arrhythmias: report of two
cases.
AB - It is still unknown whether there is an association between the use of
certolizumab pegol (CZP) in rheumatic patients and the onset of cardiac
arrhythmias. We describe the cases of two patients with rheumatoid arthritis (RA)
treated with CZP as the first-line biological drug and methotrexate (MTX), who
developed an arrhythmic event. The first was a 60-year-old, hypertensive male
smoker, the second a 66-year-old dyslipidemic female non-smoker. Both were
diagnosed as having RA in 2010, and started treatment with MTX plus CZP. The
first patient developed undatable atrial fibrillation, which was resistant to
pharmacological treatment and electrical cardioversion. The second patient
developed an atrial flutter, which was treated with a betablocker. In both cases,
we set a cautious interval between two consecutive administrations of CZP and, in
the first case, also reduced the dose of MTX without any worsening of RA
activity. Although many studies have shown that tumor necrosis factor (TNF)-alpha
plays a pathogenetic role in inducing an arrhythmogenic substrate that is
apparently rescued by anti-TNF drugs, there is still a lack of conclusive data.
We suggest caution in any patient developing a cardiac event (including rhythm
disorders) during treatment with a conventional or biological disease-modifying
anti-rheumatic drug.
PMID- 27608801
TI - Critical finger ischemia and myocardial fibrosis development after sudden
interruption of sildenafil treatment in a systemic sclerosis patient.
AB - Systemic sclerosis (SSc) is a connective tissue disease frequently associated
with Raynaud's Phenomenon (RP). Among possible pharmacological treatments,
phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive
RP. We present the case of a male SSc patient wh presented with critical finger
ischemia and concomitant appearance of myocardial fibrosis after sudden
interruption of sildenafil treatment.
PMID- 27608802
TI - Severe psoriatic dactylitis: when psoriasis involves beyond the skin.
AB - Not available.
PMID- 27608803
TI - Efficacy of high-dose methylprednisolone pulses in a child with noninfectious
persistent pleuropericarditis revealing systemic juvenile idiopathic arthritis.
AB - Not available.
PMID- 27608804
TI - Retraction Note to: Gene expression analysis indicates CB1 receptor upregulation
in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after
single-dose MDMA administration in Dark Agouti rats.
PMID- 27608805
TI - Maternal morbidity associated with violence and maltreatment from husbands and in
laws: findings from Indian slum communities.
AB - BACKGROUND: Intimate partner violence (IPV) victimization is linked to a broad
range of negative maternal health outcomes. However, it is unclear whether IPV is
directly related to poor maternal outcomes or whether IPV is a marker for other
forms of chronic, mundane maltreatment of women that stem from the culture of
gender inequity that also gives rise to IPV. To determine the prevalence of non
violent forms of gender-based household maltreatment by husbands and in-laws
(GBHM), and violence from in-laws (ILV) and husbands (IPV) against women during
the peripregnancy period (during and in the year prior to pregnancy); to assess
relative associations of GBHM, ILV and IPV with maternal health. METHODS: Cross
sectional data were collected from women <6 months postpartum (n = 1,039, ages 15
35 years) seeking child immunization in Mumbai, India. Associations of IPV, ILV
and GBHM during the peripregnancy period with maternal health (prenatal care in
first trimester, no weight gain, pain during intercourse, high blood pressure,
vaginal bleeding, premature rupture of membranes, premature birth) were
evaluated. RESULTS: One in three women (34.0 %) reported IPV, 4.8 % reported ILV,
and 48.5 % reported GBHM during the peripregnancy period. After adjusting for
other forms of abuse, IPV related to pain during intercourse (AOR = 1.79); ILV
related to not receiving first trimester antenatal care (AOR = 0.49), and GBHM
remained associated with premature rupture of membranes (AOR = 2.28), pain during
intercourse (AOR = 1.60), and vaginal bleeding (AOR = 1.80). CONCLUSION: After
adjusting for ILV and IPV, peripregnancy GBHM remained significantly associated
with multiple forms of maternal morbidity, suggesting that GBHM is a prevalent
and reliable indicator of maternal health risk.
PMID- 27608806
TI - Essential functions linked with structural disorder in organisms of minimal
genome.
AB - Intrinsically disordered regions (IDRs) of proteins fulfill important regulatory
roles in most organisms. However, the proteins of certain endosymbiont and
intracellular pathogenic bacteria with extremely reduced genomes contain
disproportionately small amounts of IDRs, consisting almost entirely of folded
domains. As their genomes co-evolving with their hosts have been reduced in
unrelated lineages, the proteomes of these bacteria represent independently
evolved minimal protein sets. We systematically analyzed structural disorder in a
representative set of such minimal organisms to see which types of functionally
relevant longer IDRs are invariably retained in them. We found that a few
characteristic functions are consistently linked with conformational disorder:
ribosomal proteins, key components of the protein production machinery, a central
coordinator of DNA metabolism and certain housekeeping chaperones seem to
strictly rely on structural disorder even in genome-reduced organisms. We propose
that these functions correspond to the most essential and probably also the most
ancient ones fulfilled by structural disorder in cellular organisms. REVIEWERS:
This article was reviewed by Michael Gromiha, Zoltan Gaspari and Sandor Pongor.
PMID- 27608807
TI - Estimation of the population attributable fraction of road-related injuries due
to speeding and passing in Iran.
AB - OBJECTIVES: Speeding and passing are considered to be the main human factors
resulting in road traffic injuries (RTIs). This study aimed to estimate the
population attributeable fraction (PAF) of speeding and passing in RTIs in rural
Iran during 2012. METHODS: The contribution of speeding and passing to RTI
related morbidity and mortality was estimated using the PAF method. The
prevalence of speeding and passing was obtained from the national traffic police
data registry. A logistic regression model was used to measure the association
between the above risk factors and RTIs. RESULTS: Speeding accounted for 20.96%
and 16.61% of rural road-related deaths and injuries, respectively. The
corresponding values for passing were 13.50% and 13.44%, respectively. Jointly,
the PAF of these factors was 31.63% for road-related deaths and 27.81% for
injuries. CONCLUSIONS: This study illustrates the importance of controlling
speeding and passing as a high-priority aspect of public-health approaches to
RTIs in Iran. It is recommended that laws restricting speeding and passing be
enforced more strictly.
PMID- 27608808
TI - Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia
pecorum-associated arthritis in Australian sheep flocks.
AB - BACKGROUND: Arthritis is an economically significant disease in lambs and is
usually the result of a bacterial infection. One of the known agents of this
disease is Chlamydia pecorum, a globally recognised livestock pathogen associated
with several diseases in sheep, cattle and other hosts. Relatively little
published information is available on the clinical, diagnostic and pathologic
features of C. pecorum arthritis in sheep, hindering efforts to enhance our
understanding of this economically significant disease. In this case series, a
combination of standard diagnostic testing used routinely by veterinarians, such
as the Chlamydia complement fixation text (CFT), veterinary clinical
examinations, and additional screening via C. pecorum specific qPCR was used to
describe putative chlamydial infections in five sheep flocks with suspected ovine
arthritis. CASE PRESENTATION: Five separate cases involving multiple lambs (aged
six to ten months) of different breeds with suspected C. pecorum arthritis are
presented. In two of the five cases, arthritic lambs exhibited marked depression
and lethargy. Arthritis with concurrent conjunctivitis was present in four out of
five lamb flocks examined. Chlamydia CFT demonstrated medium to high positive
antibody titres in all flocks examined. C. pecorum shedding was evident at
multiple sites including the conjunctiva, rectum and vagina, as determined via
qPCR. Two of the five flocks received antimicrobials and all flocks recovered
uneventfully regardless of treatment. CONCLUSION: This case series highlights the
features a field veterinarian may encounter in cases of suspected ovine
chlamydial arthritis. Our analysis suggests a presumptive diagnosis of chlamydial
arthritis in lambs can be made when there is evidence of joint stiffness with or
without synovial effusion and elevated chlamydia antibody titres. C. pecorum
specific qPCR was found to be a useful ancillary diagnostic tool, detecting
Chlamydia positivity in low or negative CFT titre animals. Variables such as
symptom duration relative to sampling, sheep breed and farm management practices
were all factors recorded that paint a complex epidemiological and diagnostic
picture for this disease. These case studies serve to provide a platform for
further research to improve diagnostic testing and new treatment and control
strategies for C. pecorum infections in sheep.
PMID- 27608811
TI - Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress
Model.
AB - BACKGROUND: Current data on antidepressant action of the N-methyl-D-aspartate
receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to
examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801,
in the social defeat stress model of depression. METHODS: The antidepressant
effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat
stress model were examined. RESULTS: In the tail suspension and forced swimming
tests, both stereoisomers significantly attenuated increased immobility time in
susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801,
significantly enhanced reduced sucrose consumption 2 or 4 days after a single
dose. However, no antianhedonia effects were detected 7 days after a single dose
of either stereoisomer. CONCLUSIONS: Both stereoisomers of MK-801 induced rapid
antidepressant effects in the social defeat stress model, although neither
produced a long-lasting effect (7 days).
PMID- 27608810
TI - Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F
F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized
States.
AB - BACKGROUND: In vivo mapping by positron emission tomography of the serotonin 1A
receptors has been hindered by the lack of suitable agonist positron emission
tomography probes. 18F-labeled F13714 is a recently developed biased agonist
positron emission tomography probe that preferentially targets subpopulations of
serotonin 1A receptors in their "active state," but its brain labeling pattern in
nonhuman primate has not been described. In addition, a potential confound in the
translatability of PET data between nonhuman animal and human arise from the use
of anesthetics that may modify the binding profiles of target receptors. METHODS:
Positron emission tomography scans were conducted in a cohort of common marmosets
(n=4) using the serotonin 1A receptor biased agonist radiotracer, 18F-F13714,
compared with a well-characterized 18F-labeled antagonist radiotracer, 18F-MPPF.
Experiments on each animal were performed under both consciousness and isoflurane
anesthesia conditions. RESULTS: 18F-F13714 binding distribution in marmosets by
positron emission tomography differs markedly from that of the 18F-MPPF. Whereas
18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed
highest labeling in other regions, including insular and cingulate cortex,
thalamus, raphe, caudate nucleus, and putamen. The binding potential values of
18F-F13714 were about one-third of those observed with 18F-MPPF, with marked
individual- and region-specific differences under isoflurane-anesthetized vs
conscious conditions. CONCLUSIONS: These findings highlight the importance of
investigating the brain imaging of serotonin 1A receptors using agonist probes
such as 18F-F13714, which may preferentially target subpopulations of serotonin
1A receptors in specific brain regions of nonhuman primate as a biased agonist.
PMID- 27608813
TI - Annular Focused Electron/Ion Beams for Combining High Spatial Resolution with
High Probe Current.
AB - This paper presents a proposal for reducing the final probe size of focused
electron/ion beam columns that are operated in a high primary beam current mode
where relatively large final apertures are used, typically required in
applications such as electron beam lithography, focused ion beams, and electron
beam spectroscopy. An annular aperture together with a lens corrector unit is
used to replace the conventional final hole-aperture, creating an annular ring
shaped primary beam. The corrector unit is designed to eliminate the first- and
second-order geometric aberrations of the objective lens, and for the same probe
current, the final geometric aberration limited spot size is predicted to be
around a factor of 50 times smaller than that of the corresponding conventional
hole-aperture beam. Direct ray tracing simulation is used to illustrate how a
three-stage core lens corrector can be used to eliminate the first- and second
order geometric aberrations of an electric Einzel objective lens.
PMID- 27608809
TI - N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for
Psychopathology.
AB - OBJECTIVE: The impact of lifetime dietary habits and their role in physical,
mental, and social well-being has been the focus of considerable recent research.
Omega-3 polyunsaturated fatty acids as a dietary constituent have been under the
spotlight for decades. Omega-3 polyunsaturated fatty acids constitute key
regulating factors of neurotransmission, neurogenesis, and neuroinflammation and
are thereby fundamental for development, functioning, and aging of the CNS. Of
note is the fact that these processes are altered in various psychiatric
disorders, including attention deficit hyperactivity disorder, depression, and
Alzheimer's disease. DESIGN: Relevant literature was identified through a search
of MEDLINE via PubMed using the following words, "n-3 PUFAs," "EPA," and "DHA" in
combination with "stress," "cognition," "ADHD," "anxiety," "depression," "bipolar
disorder," "schizophrenia," and "Alzheimer." The principal focus was on the role
of omega-3 polyunsaturated fatty acids throughout the lifespan and their
implication for psychopathologies. Recommendations for future investigation on
the potential clinical value of omega-3 polyunsaturated fatty acids were
examined. RESULTS: The inconsistent and inconclusive results from randomized
clinical trials limits the usage of omega-3 polyunsaturated fatty acids in
clinical practice. However, a body of literature demonstrates an inverse
correlation between omega-3 polyunsaturated fatty acid levels and quality of
life/ psychiatric diseases. Specifically, older healthy adults showing low
habitual intake of omega-3 polyunsaturated fatty acids benefit most from
consuming them, showing improved age-related cognitive decline. CONCLUSIONS:
Although further studies are required, there is an exciting and growing body of
research suggesting that omega-3 polyunsaturated fatty acids may have a potential
clinical value in the prevention and treatment of psychopathologies.
PMID- 27608812
TI - HMGB4 is expressed by neuronal cells and affects the expression of genes involved
in neural differentiation.
AB - HMGB4 is a new member in the family of HMGB proteins that has been characterized
in sperm cells, but little is known about its functions in somatic cells. Here we
show that HMGB4 and the highly similar rat Transition Protein 4 (HMGB4L1) are
expressed in neuronal cells. Both proteins had slow mobility in nucleus of living
NIH-3T3 cells. They interacted with histones and their differential expression in
transformed cells of the nervous system altered the post-translational
modification statuses of histones in vitro. Overexpression of HMGB4 in HEK 293T
cells made cells more susceptible to cell death induced by topoisomerase
inhibitors in an oncology drug screening array and altered variant composition of
histone H3. HMGB4 regulated over 800 genes in HEK 293T cells with a p-value
<=0.013 (n = 3) in a microarray analysis and displayed strongest association with
adhesion and histone H2A -processes. In neuronal and transformed cells HMGB4
regulated the expression of an oligodendrocyte marker gene PPP1R14a and other
neuronal differentiation marker genes. In conclusion, our data suggests that
HMGB4 is a factor that regulates chromatin and expression of neuronal
differentiation markers.
PMID- 27608815
TI - The demonstration of significant ferroelectricity in epitaxial Y-doped HfO2 film.
AB - Ferroelectricity and Curie temperature are demonstrated for epitaxial Y-doped
HfO2 film grown on (110) yttrium oxide-stabilized zirconium oxide (YSZ) single
crystal using Sn-doped In2O3 (ITO) as bottom electrodes. The XRD measurements for
epitaxial film enabled us to investigate its detailed crystal structure including
orientations of the film. The ferroelectricity was confirmed by electric
displacement filed - electric filed hysteresis measurement, which revealed
saturated polarization of 16 MUC/cm(2). Estimated spontaneous polarization based
on the obtained saturation polarization and the crystal structure analysis was 45
MUC/cm(2). This value is the first experimental estimations of the spontaneous
polarization and is in good agreement with the theoretical value from first
principle calculation. Curie temperature was also estimated to be about 450
degrees C. This study strongly suggests that the HfO2-based materials are
promising for various ferroelectric applications because of their comparable
ferroelectric properties including polarization and Curie temperature to
conventional ferroelectric materials together with the reported excellent
scalability in thickness and compatibility with practical manufacturing
processes.
PMID- 27608814
TI - MicroRNA-302 switch to identify and eliminate undifferentiated human pluripotent
stem cells.
AB - The efficiency of pluripotent stem cell differentiation is highly variable, often
resulting in heterogeneous populations that contain undifferentiated cells. Here
we developed a sensitive, target-specific, and general method for removing
undesired cells before transplantation. MicroRNA-302a-5p (miR-302a) is highly and
specifically expressed in human pluripotent stem cells and gradually decreases to
basal levels during differentiation. We synthesized a new RNA tool, miR-switch,
as a live-cell reporter mRNA for miR-302a activity that can specifically detect
human induced pluripotent stem cells (hiPSCs) down to a spiked level of 0.05% of
hiPSCs in a heterogeneous population and can prevent teratoma formation in an in
vivo tumorigenicity assay. Automated and selective hiPSC-elimination was achieved
by controlling puromycin resistance using the miR-302a switch. Our system
uniquely provides sensitive detection of pluripotent stem cells and partially
differentiated cells. In addition to its ability to eliminate undifferentiated
cells, miR-302a switch also holds great potential in investigating the dynamics
of differentiation and/or reprograming of live-cells based on intracellular
information.
PMID- 27608816
TI - Ethnic Comparison of 30-Day Potentially Preventable Readmissions After Stroke in
Hawaii.
AB - BACKGROUND AND PURPOSE: Ethnic disparities in readmission after stroke have been
inadequately studied. We sought to compare potentially preventable readmissions
(PPR) among a multiethnic population in Hawaii. METHODS: Hospitalization data in
Hawaii from 2007 to 2012 were assessed to compare ethnic differences in 30-day
PPR after stroke-related hospitalizations. Multivariable models using logistic
regression were performed to assess the impact of ethnicity on 30-day PPR after
controlling for age group (<65 and >=65 years), sex, insurance, county of
residence, substance use, history of mental illness, and Charlson Comorbidity
Index. RESULTS: Thirty-day PPR was seen in 840 (8.4%) of 10 050 any stroke
related hospitalizations, 712 (8.7%) of 8161 ischemic stroke hospitalizations,
and 128 (6.8%) of 1889 hemorrhagic stroke hospitalizations. In the multivariable
models, only the Chinese ethnicity, compared with whites, was associated with 30
day PPR after any stroke hospitalizations (odds ratio [OR] [95% confidence
interval {CI}], 1.40 [1.05-1.88]) and ischemic stroke hospitalizations (OR, 1.42
[CI, 1.04-1.96]). When considering only one hospitalization per individual, the
impact of Chinese ethnicity on PPR after any stroke hospitalization (OR, 1.22
[CI, 0.89-1.68]) and ischemic stroke hospitalization (OR, 1.21 [CI, 0.86-1.71])
was attenuated. Other factors associated with 30-day PPR after any stroke
hospitalizations were Charlson Comorbidity Index (per unit increase) (OR, 1.21
[CI, 1.18-1.24]), Medicaid (OR, 1.42 [CI, 1.07-1.88]), Hawaii county (OR, 0.78
[CI, 0.62-0.97]), and mental illness (OR, 1.37 [CI, 1.10-1.70]). CONCLUSIONS: In
Hawaii, Chinese may have a higher risk of 30-day PPR after stroke compared with
whites. However, this seems to be driven by the high number of repeated PPR
within the Chinese ethnic group.
PMID- 27608817
TI - Parental Care-Seeking Behavior and Prehospital Timelines of Care in Childhood
Arterial Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Taking appropriate action in the prehospital setting is
important for rapid stroke diagnosis in adults. Data are lacking for children. We
aimed to describe parental care-seeking behavior and prehospital timelines of
care in childhood arterial ischemic stroke. METHODS: A structured questionnaire
was developed, using value-focused event-driven conceptual modeling techniques,
to interview parents of children presenting to the emergency department with
arterial ischemic stroke from 2008 to 2014. RESULTS: Twenty-five parents (median
age 41 years, interquartile range 36-45) were interviewed. Twenty-four children
were awake, and 1 child was asleep at stroke onset; 23 had sudden onset symptoms.
Location at stroke onset included home (72%), school (8%), or other setting
(20%). Carergivers present included parent (76%), another child (8%), teacher
(4%), or alone (8%). Eighty-four percent of parents thought symptoms were
serious, and 83% thought immediate action was required, but only 48% considered
the possibility of stroke. Initial actions included calling an ambulance (36%),
wait and see (24%), calling a general practitioner (16%) or family member (8%),
and driving to the emergency department or family physician (both 8%). Median
time from onset to emergency department arrival was 76 minutes (interquartile
range 53-187), being shorter for ambulance-transported patients. CONCLUSIONS:
Stroke recognition and care-seeking behavior are suboptimal, with less than half
the parents considering stroke or calling an ambulance. Initiatives are required
to educate parents about appropriate actions to facilitate time-critical
interventions.
PMID- 27608818
TI - Preventive Suboccipital Decompressive Craniectomy for Cerebellar Infarction: A
Retrospective-Matched Case-Control Study.
AB - BACKGROUND AND PURPOSE: No evidence is available on the benefits of preventive
suboccipital decompressive craniectomy (SDC) for patients with cerebellar
infarction. The purpose of this matched case-control study was to investigate
whether preventive SDC was associated with good clinical outcomes in patients
with cerebellar infarction and to evaluate its predisposing factors. METHODS:
Between March 2007 and September 2015, 28 patients underwent preventive SDC. We
performed propensity score matching to establish a proper control group among 721
patients with cerebellar infarction during the same period. Group A (n=28)
consists of those who underwent preventive SDC, and group B (n=56) consists of
those who did not undergo preventive SDC. We analyzed and compared clinical
outcomes between groups. RESULTS: Clinical outcomes were better in group A than
in group B at discharge (P=0.048) and 12-month follow-up (P=0.030). Group B had
more deaths within 12 months than group A (log-rank, P<0.05). Logistic regression
analysis showed that preventive SDC (odds ratio, 4.815; P=0.009) and the absence
of brain stem infarction (odds ratio, 2.862; P=0.033) were independently
associated with favorable outcomes (modified Rankin Scale score of 0-2) at 12
month follow-up. CONCLUSIONS: Favorable clinical outcomes including overall
survival can be expected after preventive SDC in patients with a volume ratio
between 0.25 and 0.33 and the absence of brain stem infarction. Among these
patients, preventive SDC might be better than the best medical treatment alone.
PMID- 27608820
TI - Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill
Patients With Intracerebral Hemorrhage.
PMID- 27608819
TI - Contralaterally Controlled Functional Electrical Stimulation Improves Hand
Dexterity in Chronic Hemiparesis: A Randomized Trial.
AB - BACKGROUND AND PURPOSE: It is unknown whether one method of neuromuscular
electrical stimulation for poststroke upper limb rehabilitation is more effective
than another. Our aim was to compare the effects of contralaterally controlled
functional electrical stimulation (CCFES) with cyclic neuromuscular electrical
stimulation (cNMES). METHODS: Stroke patients with chronic (>6 months) moderate
to severe upper extremity hemiparesis (n=80) were randomized to receive 10
sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20
sessions of functional task practice in the laboratory for 12 weeks. The task
practice for the CCFES group was stimulation assisted. The primary outcome was
change in Box and Block Test (BBT) score at 6 months post treatment. Upper
extremity Fugl-Meyer and Arm Motor Abilities Test were also measured. RESULTS: At
6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6
(95% confidence interval [CI], 2.2-7.0), than the cNMES group, 1.8 (95% CI, 0.6
3.0), between-group difference of 2.8 (95% CI, 0.1-5.5), P=0.045. No significant
between-group difference was found for the upper extremity Fugl-Meyer (P=0.888)
or Arm Motor Abilities Test (P=0.096). Participants who had the largest
improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand
impairment at baseline. Among these, the 6-month post-treatment BBT gains of the
CCFES group, 9.6 (95% CI, 5.6-13.6), were greater than those of the cNMES group,
4.1 (95% CI, 1.7-6.5), between-group difference of 5.5 (95% CI, 0.8-10.2),
P=0.023. CONCLUSIONS: CCFES improved hand dexterity more than cNMES in chronic
stroke survivors. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00891319.
PMID- 27608821
TI - Safety and Preliminary Efficacy of Early Tirofiban Treatment After Alteplase in
Acute Ischemic Stroke Patients.
AB - BACKGROUND AND PURPOSE: We investigated whether early initiation of tirofiban, a
glycoprotein IIb/IIIa antagonist, is safe, can reduce the risk of reocclusion,
and improve outcomes in acute ischemic stroke patients after alteplase. METHODS:
Forty-one patients received alteplase followed by intravenous tirofiban infusion
for at least 24 hours. The incidence of symptomatic intracranial hemorrhage,
systematic bleedings, and death was recorded. The National Institutes of Health
stroke scale score was evaluated at 24 hours and at day 7 (or discharge).
Modified Rankin scale was assessed at 3 months. Outcomes for these patients were
compared with a propensity score-matched historical cohort with alteplase only.
RESULTS: The incidence of symptomatic intracranial hemorrhage, death, or
systematic bleedings (P=1.00) was not increased in the alteplase/tirofiban group.
At 24 hours, fewer patients experienced reocclusion in the alteplase/tirofiban
group (2.4% versus 22.0%; P=0.025). At day 7 or discharge, the median National
Institutes of Health stroke scale score was significantly lower in the
alteplase/tirofiban group (1 versus 6; P=0.002). At 3 months, more patients had
favorable outcomes of modified Rankin scale 0 to 1 (70.7% versus 46.2%; P=0.026).
CONCLUSIONS: Intravenous tirofiban immediately after alteplase seems to be safe
and potentially more effective when compared with alteplase alone for selected
stroke patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/.
Unique identifier: ChiCTR-TRC-14004630.
PMID- 27608823
TI - An extended patch-dynamic framework for food chains in fragmented landscapes.
AB - Habitat destruction, a key determinant of species loss, can be characterized by
two components, patch loss and patch fragmentation, where the former refers to
the reduction in patch availability, and the latter to the division of the
remaining patches. Classical metacommunity models have recently explored how food
web dynamics respond to patch loss, but the effects of patch fragmentation have
largely been overlooked. Here we develop an extended patch-dynamic model that
tracks the patch occupancy of the various trophic links subject to colonization
extinction-predation dynamics by incorporating species dispersal with patch
connectivity. We found that, in a simple food chain, species at higher trophic
level become extinct sooner with increasing patch loss and fragmentation due to
the constraint in resource availability, confirming the trophic rank hypothesis.
Yet, effects of fragmentation on species occupancy are largely determined by
patch loss, with maximal fragmentation effects occurring at intermediate patch
loss. Compared to the spatially explicit simulations that we also performed, the
current model with pair approximation generates similar community patterns
especially in spatially clustered landscapes. Overall, our extended framework can
be applied to model more complex food webs in fragmented landscapes, broadening
the scope of existing metacommunity theory.
PMID- 27608822
TI - Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke
Clinical Trials.
AB - BACKGROUND AND PURPOSE: Despite several national coordinated research networks,
enrollment in many cerebrovascular trials remains challenging. An electronic tool
was needed that would improve the efficiency and efficacy of screening for
multiple simultaneous acute clinical stroke trials by automating the evaluation
of inclusion and exclusion criteria, improving screening procedures and
streamlining the communication process between the stroke research coordinators
and the stroke clinicians. METHODS: A multidisciplinary group consisting of
physicians, study coordinators, and biostatisticians designed and developed an
electronic clinical trial screening tool on a HIPAA (Health Insurance Portability
and Accountability Act)-compliant platform. RESULTS: A web-based tool was
developed that uses branch logic to determine eligibility for simultaneously
enrolling clinical trials and automatically notifies the study coordinator teams
about eligible patients. After 12 weeks of use, 225 surveys were completed, and
51 patients were enrolled in acute stroke clinical trials. Compared with the 12
weeks before implementation of the tool, there was an increase in enrollment from
16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and
coordinators reported increased satisfaction with the process and improved ease
of screening. CONCLUSIONS: We created a semiautomated electronic screening tool
that uses branch logic to screen patients for stroke clinical trials. The tool
has improved efficiency and efficacy of screening, and it could be adapted for
use at other sites and in other medical fields.
PMID- 27608824
TI - Erratum to: Developing a mHealth intervention to promote uptake of HIV testing
among African communities in the UK: a qualitative study.
PMID- 27608825
TI - Tracking Optical and Electronic Behaviour of Quantum Contacts in Sub-Nanometre
Plasmonic Cavities.
AB - Plasmonic interactions between two metallic tips are dynamically studied in a
supercontinuum dark-field microscope and the transition between coupled and
charge-transfer plasmons is directly observed in the sub-nm regime. Simultaneous
measurement of the dc current, applied force, and optical scattering as the tips
come together is used to determine the effects of conductive pathways within the
plasmonic nano-gap. Critical conductances are experimentally identified for the
first time, determining the points at which quantum tunnelling and conductive
charge transport begin to influence plasmon coupling. These results advance our
understanding of the relationship between conduction and plasmonics, and the
fundamental quantum mechanical behaviours of plasmonic coupling.
PMID- 27608826
TI - Electrospun carbon nanofibers reinforced 3D porous carbon polyhedra network
derived from metal-organic frameworks for capacitive deionization.
AB - Carbon nanofibers reinforced 3D porous carbon polyhedra network (e-CNF-PCP) was
prepared through electrospinning and subsequent thermal treatment. The
morphology, structure and electrochemical performance of the e-CNF-PCP were
characterized using scanning electron microscopy, Raman spectra, nitrogen
adsorption-desorption, cyclic voltammetry and electrochemical impedance
spectroscopy, and their electrosorption performance in NaCl solution was studied.
The results show that the e-CNF-PCP exhibits a high electrosorption capacity of
16.98 mg g(-1) at 1.2 V in 500 mg l(-1) NaCl solution, which shows great
improvement compared with those of electrospun carbon nanofibers and porous
carbon polyhedra. The e-CNF-PCP should be a very promising candidate as electrode
material for CDI applications.
PMID- 27608827
TI - Fasciolosis in South America: epidemiology and control challenges.
AB - Fasciolosis caused by Fasciola hepatica severely affects the efficiency of
livestock production systems worldwide. In addition to the economic impact
inflicted on livestock farmers, fasciolosis is an emergent zoonosis. This review
emphasizes different aspects of the disease in South America. Available data on
epidemiology in bovines and ovines in different countries, as well as a growing
body of information on other domestic and wildlife definitive hosts, are
summarized. The issue of drug resistance that compromises the long-term
sustainability of current pharmacological strategies is examined from a regional
perspective. Finally, efforts to develop a single-antigen recombinant vaccine in
ruminants are reviewed, focusing on the cases of leucine aminopeptidase or
thioredoxin glutathione reductase.
PMID- 27608828
TI - Institutional analysis of health promotion for older people in Europe - concept
and research tool.
AB - BACKGROUND: European societies are ageing rapidly and thus health promotion for
older people (HP4OP) is becoming an increasingly relevant issue. Crucial here is
not only the clinical aspect of health promotion but also its organisational and
institutional dimension. The latter has been relatively neglected in research on
HP4OP. This issue is addressed in this study, constituting a part of the EU
project ProHealth65+, engaging ten member countries. This paper is based on two
intertwining research goals: (1) exploring which institutions/organisations are
performing HP4OP activities in selected European countries (including sectors
involved, performed roles of these institutions, organisation of those
activities); (2) developing an institutional approach to HP4OP. Thus, the paper
provides a description of the analytical tools for further research in this area.
METHODS: The mentioned aims were addressed through the mutual use of two
complementary methods: (a) a literature review of scientific and grey literature;
and (b) questionnaire survey with selected expert respondents from 10 European
countries. The expert respondents, selected by the project's collaborating
partners, were asked to fill in a custom designed questionnaire concerning HP4OP
institutional aspects. RESULTS: The literature review provided an overview of the
organisational arrangements in different HP4OP initiatives. It also enabled the
development of functional institutional definitions of health promotion, health
promotion activities and interventions, as well as an institutional definition
adequate to the health promotion context. The distinctions between sectors were
also clarified. The elaborated questionnaires provided in-depth information on
countries specifically indicating the key sectors involved in HP4OP in those
selected countries. These are: health care, regional/local authorities,
NGO's/voluntary institutions. The questionnaire and literature review both
resulted in the indication of a significant level of cross-sectorial cooperation
in HP4OP. CONCLUSIONS: The inclusion of the institutional analysis within the
study of HP4OP provides a valuable opportunity to analyse, in a systematic way,
good practices in this respect, also in terms of institutional arrangements. A
failure to address this aspect in policymaking might potentially cause
organisational failure even in evidence-based programmes. This paper frames the
perception of this problem.
PMID- 27608829
TI - Development of a Mobile Phone-Based Weight Loss Lifestyle Intervention for
Filipino Americans with Type 2 Diabetes: Protocol and Early Results From the
PilAm Go4Health Randomized Controlled Trial.
AB - BACKGROUND: Filipino Americans are the second largest Asian subgroup in the
United States, and were found to have the highest prevalence of obesity and type
2 diabetes (T2D) compared to all Asian subgroups and non-Hispanic whites. In
addition to genetic factors, risk factors for Filipinos that contribute to this
health disparity include high sedentary rates and high fat diets. However,
Filipinos are seriously underrepresented in preventive health research. Research
is needed to identify effective interventions to reduce Filipino diabetes risks,
subsequent comorbidities, and premature death. OBJECTIVE: The overall goal of
this project is to assess the feasibility and potential efficacy of the Filipino
Americans Go4Health Weight Loss Program (PilAm Go4Health). This program is a
culturally adapted weight loss lifestyle intervention, using digital technology
for Filipinos with T2D, to reduce their risk for metabolic syndrome. METHODS:
This study was a 3-month mobile phone-based pilot randomized controlled trial
(RCT) weight loss intervention with a wait list active control, followed by a 3
month maintenance phase design for 45 overweight Filipinos with T2D. Participants
were randomized to an intervention group (n=22) or active control group (n=23),
and analyses of the results are underway. The primary outcome will be percent
weight change of the participants, and secondary outcomes will include changes in
waist circumference, fasting plasma glucose, glycated hemoglobin A1c, physical
activity, fat intake, and sugar-sweetened beverage intake. Data analyses will
include descriptive statistics to describe sample characteristics and a
feasibility assessment based on recruitment, adherence, and retention. Chi
square, Fisher's exact tests, t-tests, and nonparametric rank tests will be used
to assess characteristics of randomized groups. Primary analyses will use
analysis of covariance and linear mixed models to compare primary and secondary
outcomes at 3 months, compared by arm and controlled for baseline levels.
RESULTS: Recruitment was completed in January, 2016, and participant follow-up
continued through June, 2016. At baseline, mean age was 57 years, 100% (45/45) of
participants self-identified as Filipinos, and the cohort was comprised of 17
males and 28 females. Overall, participants were obese with a baseline mean body
mass index of 30.2 kg/m2 (standard deviation 4.9). The majority of participants
were immigrants (84%, 38/45), with 47% (21/45) living in the United States for
more than 10 years. One third of all participants (33%, 15/45) had previously
used a pedometer. CONCLUSIONS: This study will provide preliminary evidence to
determine if the PilAm Go4Health weight loss lifestyle intervention is feasible,
and if the program demonstrates potential efficacy to reduce risks for metabolic
syndrome in Filipinos with T2D. Positive results will lend support for a larger
RCT to evaluate the effectiveness of the PilAm Go4Health intervention for
Filipinos. CLINICALTRIAL: ClinicalTrials.gov: NCT02290184;
https://clinicaltrials.gov/ct2/show/NCT02290184 (Archived at
http://www.webcitation.org/6k1kUqKSP).
PMID- 27608830
TI - Frequency and clinical relevance of potential cytochrome P450 drug interactions
in a psychiatric patient population - an analysis based on German insurance
claims data.
AB - BACKGROUND: Numerous drugs used in the treatment of psychiatric disorders are
substrates of cytochrome P450 enzymes and are potential candidates for drug-drug
interactions (DDIs). METHODS: Claims data of a German statutory health insurance
company from severely mentally ill patients who registered in an integrated care
contract from August 2004 to December 2009 were analysed. We measured time
periods of concomitant prescription of drugs that have been reported to interact
via cytochrome P450, with a focus on drugs acting as strong inhibitors. Such drug
drug exposure (DDE) is an incontrovertible precursor of DDIs. We assessed whether
potential DDIs were considered clinically relevant based on the prescribing
information of the respective drugs. RESULTS: Among all 1221 patients, 186
patients (15.2 %; Clopper-Pearson 95 % confidence interval (CI): 13.3-17.4 %) had
at least one DDE prescription, and 58 patients (4.8 %; 95 % CI 3.6-6.1) had at
least one DDE prescription involving a strong cytochrome P450 inhibitor. In 59
patients, (4.8 %; 95 % CI: 3.7-6.2 %) five or more DDEs were identified, and five
or more DDEs with a strong inhibitor were identified in 18 patients (1.5 %; 95 %
CI: 0.9-2.3). The rates of DDEs were 0.27 (Garwood 95%CI: 0.25-0.28) per person
year and 0.07 (95 % CI: 0.07-0.08) for strong-inhibitor DDEs. Four of the ten
most frequent DDEs were identified as clinically relevant, and seven of the eight
most frequent DDEs involving a strong inhibitor were clinically relevant.
CONCLUSIONS: The number of patients with DDEs was not alarmingly high in our
sample. Nevertheless, prescription information showed that some prescribed drug
combinations could result in serious adverse consequences that are known to
weaken or strengthen the effect of the drugs and should therefore be avoided.
PMID- 27608832
TI - UK parliamentary debate analysis: bombing ISIL in Syria.
AB - This paper examines the arguments presented for and against the UK government's
motion for the UK to intervene militarily in Syria in the House of Commons debate
on ISIL in Syria that took place on 2 December 2015. It considers what the most
common arguments were in favour of and in opposition to the motion as well as
which arguments were given the most emphasis, in order to understand the prime
justifications given that led to the decision to approve the motion. It suggests
that due to the shadow of the 2003 Iraq war, politicians in the debate placed a
considerable emphasis on the legal justification for military intervention. It
argues that the focus on the national security of the UK and its allies in this
particular debate seems to contrast with previous military interventions where
humanitarian motives were more widely stated. This paper calls for further
comparative research of parliamentary debates in order to track such changes in
the rhetoric used by UK politicians to defend their support for military
intervention.
PMID- 27608831
TI - Peripheral thyroid hormone levels and hepatic thyroid hormone deiodinase gene
expression in dairy heifers on the day of ovulation and during the early peri
implantation period.
AB - BACKGROUND: Before the onset of fetal thyroid hormone production, the
transplacental delivery of maternal thyroid hormones is necessary for embryonic
and fetal development. Therefore, the adaptation of maternal thyroid hormone
metabolism may be important for pregnancy success and embryo survival. The aims
of this study were to determine the thyroid hormone levels during the early peri
implantation period until day 18 and on the day of ovulation, to determine
whether pregnancy success is dependent on a "normothyroid status" and to
determine whether physiological adaptations in maternal thyroid hormone
metabolism occur, which may be necessary to provide sufficient amounts of
biologically active T3 to support early pregnancy. Therefore, blood samples
obtained on the day of ovulation (day 0) and days 14 and 18 of the Holstein
Friesian heifers (n = 10) during the respective pregnant, non-pregnant and
negative control cycles were analyzed for thyroid-stimulating-hormone (TSH),
thyroxine (T4) and triiodothyronine (T3). Liver biopsies (day 18) from pregnant
and respective non-pregnant heifers were analyzed for mRNA expression of the most
abundant hepatic thyroid hormone deiodinase (DIO1) by real time qPCR. RESULTS:
Although liver DIO1 mRNA expression did not differ between the pregnant and non
pregnant heifers on day 18, the serum concentrations of TSH and T3 on day 18 were
higher in non-pregnant heifers compared to pregnant heifers (P < 0.05). Moreover,
T3 decreased between day 0 and 18 in pregnant heifers (P < 0.001). CONCLUSIONS:
In conclusion, no associations between thyroid hormone patterns on day 18 and
pregnancy success were detected. During the early peri-implantation period, TSH
and T3 may be affected by the pregnancy status because both TSH and T3 were lower
on day 18 in pregnant heifers compared to non-pregnant dairy heifers. In further
studies, the thyroid hormone axis should be evaluated throughout the entire
gestation to confirm these data and identify other possible effects of pregnancy
on the thyroid hormone axis in cattle.
PMID- 27608833
TI - Is the Keros classification alone enough to identify patients with the 'dangerous
ethmoid'? An anatomical study.
AB - CONCLUSION: By means of three-dimensional display of the critical measurements,
the authors suggest a novel definition of 'dangerous ethmoid'. Parallel to Keros
type III, the proposed determining factors include: olfactory fossa width >6 mm,
its distance to the medial nasal concha (turbinate) <20 mm and to the orbit
interval of <10 mm. Clinical evaluation of these preliminary criteria based only
on radiological data is required and underway. OBJECTIVES: Detailed pre-operative
assessment of sinus computer tomography (CT) scans reduces the frequency of
severe complications in patients undergoing endoscopic sinus surgery (ESS). The
authors aimed to identify a sub-set of anatomical features pre-disposing to major
post-operative complications. METHOD: Sinus computer tomography (CT) scans of
patients of a single institution qualified for ESS were examined. Besides the
Keros classification, authors focused on the anatomic measurements as follows:
the olfactory fossa depth, width, and its distance from the medial nasal concha
and the medial wall of the orbit (referred to as 'critical measurements'). The
sample comprised 120 consecutive CT exams, without clinical validation. RESULTS:
Keros type I, II, and III was noted in 9.2%, 75.8%, and 15.0% of cases,
respectively. Despite some statistically significant correlations, it was not
possible to identify the patient age, sex, and side of body clearly correlating
with the critical measurements.
PMID- 27608834
TI - Cabazitaxel and indocyanine green co-delivery tumor-targeting nanoparticle for
improved antitumor efficacy and minimized drug toxicity.
AB - Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many
kinds of cancers. However, the poor water solubility remains a serious deterrent
to the utilization of CBX as a commercial drug. In this study, we designed a
strategy that integrated CBX into albumin nanoparticles (ANs) formed with human
serum albumin (HSA) to improve the water solubility and targeting ability.
Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could
cooperate with CBX to enhance the antitumor effect. The obtained ANs containing
ICG and CBX (AN-ICG-CBX) exhibited good mono-dispersity. In vitro cytotoxicity
study showed the effectiveness of CBX and ICG, respectively, whereas AN-ICG-CBX
with irradiation exhibited the most efficient antiproliferative ability (83.7%).
In vivo safety evaluation studies demonstrated the safety of AN-ICG-CBX.
Furthermore, the in vivo antitumor study indicated that the AN-ICG-CBX with
irradiation achieved higher tumor inhibition rate (91.3%) compared with CBX
encapsulated AN (AN-CBX) (83.3%) or ICG-encapsulated AN (AN-ICG) plus irradiation
(60.1%) in 4T1 tumor-bearing mice. To sum up, a safety and effective formulation
AN-ICG-CBX was developed in this study and successfully reduced the drug
toxicity, improved the targeting efficiency and enhanced the therapeutic effects,
becoming a promising candidate for clinical application.
PMID- 27608836
TI - Rough gold films as broadband absorbers for plasmonic enhancement of TiO2
photocurrent over 400-800 nm.
AB - Recent years have witnessed an increasing interest in highly-efficient absorbers
of visible light for the conversion of solar energy into electrochemical energy.
This study presents a TiO2-Au bilayer that consists of a rough Au film under a
TiO2 film, which aims to enhance the photocurrent of TiO2 over the whole visible
region and may be the first attempt to use rough Au films to sensitize TiO2.
Experiments show that the bilayer structure gives the optimal optical and
photoelectrochemical performance when the TiO2 layer is 30 nm thick and the Au
film is 100 nm, measuring the absorption 80-90% over 400-800 nm and the
photocurrent intensity of 15 MUA.cm(-2), much better than those of the TiO2-AuNP
hybrid (i.e., Au nanoparticle covered by the TiO2 film) and the bare TiO2 film.
The superior properties of the TiO2-Au bilayer can be attributed to the rough Au
film as the plasmonic visible-light sensitizer and the photoactive TiO2 film as
the electron accepter. As the Au film is fully covered by the TiO2 film, the TiO2
Au bilayer avoids the photocorrosion and leakage of Au materials and is expected
to be stable for long-term operation, making it an excellent photoelectrode for
the conversion of solar energy into electrochemical energy in the applications of
water splitting, photocatalysis and photosynthesis.
PMID- 27608837
TI - Faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae
and Shiga toxin-producing Escherichia coli in asymptomatic nursery children in
Lower Saxony (Germany), 2014.
AB - Children may be at higher risk for carriage of antimicrobial-resistant bacteria
because of higher usage of antimicrobials. They also have higher rates of Shiga
toxin-producing Escherichia coli (STEC) infections than other population groups.
Some infections, particularly in children, are asymptomatic, but still lead to
the excretion of large numbers of bacteria and viruses that may cause clinical
disease in other individuals. That is one reason why, in Lower Saxony as in other
German federal states - asymptomatic carriers of STEC are excluded from nurseries
and schools until three consecutive stool samples test negative in order to
prevent secondary cases. The prevalence of children who are asymptomatic STEC
carriers is unknown. But if it is high, this measure would have substantial
socioeconomic effects on families. Infections with extended-spectrum beta
lactamase-producing Enterobacteriaceae (ESBL-E) are an increasing problem for
public health, especially for hospitals. However, there are no reliable estimates
of the prevalence of asymptomatic ESBL-E carriers in Lower Saxony, as there is no
mandatory requirement to report these carriers. In order to discuss the exclusion
policies for children attending nurseries and ascertain a baseline of ESBL-E
carriers, we conducted a cross-sectional study. The aim was to determine the
prevalence of ESBL-E and STEC and identify risk factors for carriage in nursery
children without diarrhoea (asymptomatic) aged 0-6 years in four selected
districts in Northern Germany. During April-September 2014, we collected stool
specimens with the support of voluntarily participating nurseries. We tested for
STEC by PCR and for ESBL-E on chromogenic agar. Questionnaires answered by
parents contained data on eating and drinking habits, outdoor activities, prior
antibiotic treatment and animal contact for each participating child. We compared
the epidemiological characteristics of ESBL-E carriers vs. non-carriers by using
univariable analysis (P value, odds ratio and 95% confidence interval). We could
not perform a statistical analysis for STEC carriers due to the low numbers of
positive STEC specimens. Of 224 asymptomatic nursery children, we found a
prevalence of 2.3% for ESBL-E carriage and 0.5% for STEC carriage. Asymptomatic
ESBL-E carriers were more likely to have consumed raw milk, have had contact with
pet rodents, or to have taken antibiotics during the preceding 6 months. We also
found a high proportion of raw milk consumption (11%). We suggest that the low
STEC prevalence in asymptomatic children supports the current practice of
excluding STEC carriers from nurseries. The association between ESBL-E carriage
and raw milk consumption and contact with pet rodents needs further
investigation.
PMID- 27608838
TI - The discovery of the lymphatics in the seventeenth century. Part iii: the
dethroning of the liver.
AB - Around 1650, the thoracic chyle duct and the serous lymph vessels were discovered
nearly simultaneously in four different places on the European continent. The new
theory was that all ingested fluid, digested food, and serous lymph liquid were
drained towards the subclavian veins, and then to the heart where they was mixed
with and transformed into blood, which had been the supposed function of the
liver. None of the discoverers proposed a valuable alternative function for the
liver. Bile formation and filtration of serum from the blood to carry it through
lymph vessels to the chyle sac (cysterna chyli) were the only remaining possible
liver functions. The liver was dethroned from its presumed function as blood
forming organ with an epitaph starting with the words 'Stay, Wayfarer, Enclosed
in this tomb is he who entombed very many'.
PMID- 27608835
TI - Interaction of MSC with tumor cells.
AB - Tumor development and tumor progression is not only determined by the
corresponding tumor cells but also by the tumor microenvironment. This includes
an orchestrated network of interacting cell types (e.g. immune cells, endothelial
cells, fibroblasts, and mesenchymal stroma/stem cells (MSC)) via the
extracellular matrix and soluble factors such as cytokines, chemokines, growth
factors and various metabolites. Cell populations of the tumor microenvironment
can interact directly and indirectly with cancer cells by mutually altering
properties and functions of the involved partners. Particularly, mesenchymal
stroma/stem cells (MSC) play an important role during carcinogenesis exhibiting
different types of intercellular communication. Accordingly, this work focusses
on diverse mechanisms of interaction between MSC and cancer cells. Moreover, some
functional changes and consequences for both cell types are summarized which can
eventually result in the establishment of a carcinoma stem cell niche (CSCN) or
the generation of new tumor cell populations by MSC-tumor cell fusion.
PMID- 27608839
TI - Development of a new stroke scale in an emergency setting.
AB - BACKGROUND: Early identification of stroke is crucial to maximize early
management benefits in emergency departments. This study aimed to develop and
validate a new stroke recognition instrument for differentiating acute stroke
from stroke mimics in an emergency setting. METHODS: A prospective observational
cohort study among suspected stroke patients presenting to Emergency Department
in the Second Affiliated Hospital of Guangzhou Medical University was conducted
from May 2012 to March 2013. The symptoms and signs of suspected stroke patients
were collected. Logistic regression analysis was used to identify the factors
associated with acute stroke. The symptoms and signs closely associated with
acute stroke were selected to develop the new stroke scale, Guangzhou Stroke
Scale (GZSS). The diagnostic value of GZSS was then compared with ROSIER, FAST
and LAPSS. The primary outcome was confirmed stroke by CT within 24 h. RESULTS:
Four hundred and sixteen suspected stroke patients (247 ischemia, 107 hemorrhage,
4 transient ischemic attack, 58 non-stroke) were assessed. A new stroke scale,
GZSS (total score from -1 to 8.5), was developed and consisted of nine
parameters: vertigo (-1), GCS <= 8 (+2), facial paralysis (+1), asymmetric arm
weakness (+1), asymmetric leg weakness (+1), speech disturbance (+0.5), visual
field defect (+1), systolic blood pressure >=145 mmHg (+1) and diastolic blood
pressure >=95 mmHg (+1). Among the four scales, the discriminatory value (C
statistic) of GZSS was the best (AUC: 0.871 (p < 0.001) when compared to ROSIER
(0.772), LAPSS (0.722) and FAST (0.699). At an optimal cut-off score of >1.5 on a
scale from -1 to 8.5, the sensitivity and specificity of GZSS were 83.2 and 74.1
%, whilst the sensitivities and specificities of ROSIER were 77.7 and 70.7 %,
FAST were 76.0 and 63.8 %, LAPSS were 56.4 and 87.9 %. CONCLUSION: GZSS had
better sensitivity than existing stroke scales in Chinese patients with suspected
stroke. Further studies should be conducted to confirm its effectiveness in the
initial differentiation of acute stroke from stroke mimics.
PMID- 27608840
TI - Overexpression of PHRF1 attenuates the proliferation and tumorigenicity of non
small cell lung cancer cells.
AB - The aim of this study was to investigate the potential role of PHRF1 in lung
tumorigenesis. Western blot analysis was used to detect the expression of
proteins. Quantitative reverse transcriptase polymerase chain reaction,
immunohistochemistry, soft agar assay and tumor formation assay in nude mice were
applied. Cell cycle distribution was analyzed by flow cytometry. The lower level
of PHRF1 mRNA was observed in human lung cancer tissues than that in
paracancerous tissues. The decreased expression of PHRF1 protein was observed in
H1299 and H1650 cell lines than that in 16HBE and BEAS-2B cell lines. The
decreased expression of PHRF1 protein was observed in malignant 16HBE cells
compared to control cells. The reduced expression of PHRF1 protein was observed
in mice lung tissues treated with BaP than that in control group. Overexpression
of PHRF1 inhibited H1299 cell proliferation, colony formation in vitro and growth
of tumor xenograft in vivo, and arrested cell cycle in G1 phase. The decreased
expression of TGIF and c-Myc proteins and the increased expression of p21 protein
were observed in H1299-PHRF1 cells compared with H1299-pvoid cells. In
conclusion, our findings suggest that overexpression of PHRF1 attenuated the
proliferation and tumorigenicity of non-small cell lung cancer cell line of
H1299.
PMID- 27608841
TI - The clinicopathological and prognostic features of Chinese and Japanese
inpatients with lung cancer.
AB - Here, we retrospectively compared the differences in clinicopathological
behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1,
n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China
Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and
Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka,
n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower
TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and
large cell carcinomas than Chinese patients (p<0.05). Survival analysis showed
that tumor size was employed as a prognostic factor for the Japanese and Chinese
cancer patients (p<0.05). In DMU and CMUS, the ratios of female patients or
adenocarcinoma were higher than other hospitals (p<0.05), while the patients from
CMUT and CMU1 were younger than the others (p<0.05). The ratios of squamous cell
carcinoma from CMUT, CMU1 and JMU were higher than the others, while it was the
same for the ratio of large and small cell carcinoma in Takaoka and CMU1
(p<0.05). TNM staging was higher in CMUT than JMU and Takaoka (p<0.05). The
female patients of lung cancer showed young prone, large tumor size, a high ratio
of adenocarcinoma and advanced TNM staging in comparison to the counterpart
(p<0.05). The younger patients of lung cancer displayed smaller tumor size,
higher ratio of adenocarcinoma, lower TNM staging than the elder in Takaoka
(p<0.05). There were more aggressive behaviors and shorter survival time for
Chinese than Japanese lung cancer patients. The prevention of lung cancer should
be strengthened by establishing a systematic and effective screening strategy,
especially for the young and female patients.
PMID- 27608842
TI - Circulating levels of C-reactive protein, interleukin-6 and tumor necrosis factor
alpha and risk of colorectal adenomas: a meta-analysis.
AB - Results from publications on inflammatory markers of C-reactive protein (CRP),
interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and risk of
colorectal adenomas are not consistent. A meta-analysis was conducted to explore
the above-mentioned associations. Relevant studies were identified by a search of
Embase, Medline and PubMed through February 2016. A random effect model was
adopted to combine study-specific odds ratio (OR) and 95% confidence interval
(95% CI). Between-study heterogeneity and publications bias were assessed. Dose
response relationships were assessed by restricted cubic splines. Nineteen
observational studies were included. For highest vs. lowest levels, results from
this meta-analysis did not support an association between circulating levels of
CRP [OR (95% CI): 1.15 (0.94-1.40)], IL-6 [1.17 (0.94-1.46)] and TNF-alpha [0.99
(0.75-1.31)] and risk of colorectal adenomas, respectively. The findings were
supported by sensitivity analysis and subgroup analysis. In dose-response
analysis, the risk of colorectal adenomas increased by 2% [1.02 (0.97-1.08)] for
each 1 mg/L increment in circulation CRP levels, 9% [1.09 (0.91-1.31)] for each 1
ng/L increment in circulation IL-6 levels, and 6% [1.06 (0.93-1.21)] for each 1
pg/mL increment in circulation TNF-alpha levels. Moderate between-study
heterogeneity was found. No evidence of publication bias was found. Circulation
levels of CRP, IL-6 and TNF-alpha might be not useful biomarkers for identifying
colorectal adenomas, respectively.
PMID- 27608843
TI - Dickkopf-1 expression is associated with tumorigenity and lymphatic metastasis in
human hilar cholangiocarcinoma.
AB - Dickkopf-1 (DKK1) is involved in tumorigenesis and the invasion of several
tumors. However, its biological function in human hilar cholangiocarcinoma (HCCA)
has not yet been documented. This study was designed to investigate the clinical
significance and biological function of DKK1 in HCCA. The expression of DKK1 was
investigated in thirty-seven human HCCA biopsy samples by immunohistochemistry.
To further explore the biological effects of DKK1 in HCCA, transient and stable
knockdown of DKK1 in two human HCCA cells (QBC939 and FRH0201) were established
using small interfering or short hairpin RNA expression vector. In the present
study, immunohistochemistry revealed that DKK1 was up-regulated in human HCCA
tissues (24/37, 64.9%). High levels of DKK1 in human HCCA correlated with
metastasis to the hilar lymph nodes (P=0.038). Genetic depletion of DKK1 in HCCA
cells resulted in significantly inhibited proliferation, colony formation and
migration compared with controls. Most importantly, DKK1 down-regulation impaired
tumor formation capacity of HCCA cells in vivo. Subsequent investigations
revealed that beta-catenin is an important target of DKK1 and DKK1 exerts its pro
invasion function at least in part through the beta-catenin/ matrix
metalloproteinase-7 (MMP-7) signaling pathway. Consistently, in human HCCA
tissues, DKK1 level was positively correlated with beta-catenin and MMP-7
expression, as well as tumor hilar lymphatic metastasis. Taken together, our
findings indicate that DKK1 may be a crucial regulator in the tumorigenicity and
invasion of human HCCA, DKK1 exerts its pro-invasion function at least in part
through the beta-catenin/ MMP-7 signaling pathway, suggesting DKK1 as a potential
therapeutic target for HCCA.
PMID- 27608844
TI - GPR30 disrupts the balance of GABAergic and glutamatergic transmission in the
spinal cord driving to the development of bone cancer pain.
AB - Cancer induced bone pain is a very complicated clinical pain states that has
proven difficult to be treated effectively due to poorly understand of underlying
mechanism, but bone cancer pain (BCP) seems to be enhanced by a state of spinal
sensitization. In the present study, we showed that carcinoma tibia implantation
induced notable pain sensitization and up-regulation of G-protein-coupled
estrogen receptor (GPR30) in the spinal cord of rats which was reversed by GPR30
knockdown. Further studies indicated that upregulation of GPR30 induced by cancer
implantation resulted in a select loss of gamma-aminobutyric acid-ergic
(GABAergic) neurons and functionally diminished the inhibitory transmission due
to reduce expression of the vesicular GABA transporter (VGAT). GPR30 contributed
to spinal cord disinhibition by diminishing the inhibitory transmission via
upregulation of alpha1 subunit and downregulation of gamma2 subunits. GPR30 also
facilitated excitatory transmission by promoting functional up-regulation of the
calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha) in
glutamatergic neurons and increasing the clustering of the glutamate receptor
subunit 1 (GluR1) subunit to excitatory synapse.Taken together, GPR30 contributed
to the development of BCP by both facilitating excitatory transmission and
inhibiting inhibitory transmission in the spinal cord. Our findings provide the
new spinal disinhibition and sensitivity mechanisms underlying the development of
bone cancer pain.
PMID- 27608845
TI - Sialylation transmogrifies human breast and pancreatic cancer cells into 3D
multicellular tumor spheroids using cyclic RGD-peptide induced self-assembly.
AB - Multicellular tumor spheroids (MTS) have been at the forefront of cancer
research, designed to mimic tumor-like developmental patterns in vitro. Tumor
growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan
structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS
formation are not well defined. Matrix-free spheroids from breast MCF-7 and
pancreatic PANC1 cancer cell lines and their respective tamoxifen (TMX) and
gemcitabine (Gem) resistant variants were generated using the RGD platform of
cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl
triphenylphosphonium bromide (cyclo-RGDfK (TPP)). MCF-7 and MCF-7 TMX cells
formed tight spheroids both in the classical agarose-and RGD-based platforms
while all PANC1 cells formed loose aggregates. Using lectin histochemistry
staining, sialidase assay, neuraminidase (Vibrio cholerae) and oseltamivir
phosphate (OP) neuraminidase inhibitor treatments, MCF-7 and PANC1 cells and
their drug-resistant variants expressed different sialic acid (SA) content on
their cell surfaces. alpha-2,3- and alpha-2,6-sialic acid surface residues
facilitated spheroid formation under cyclo-RGDfK(TPP)-induced self-assembly.
Pretreatment with alpha-2,3- SA specific Maackia amurensis (MAL-II) lectin, alpha
2,6-SA specific Sambucus nigra (SNA) lectin, and exogenous alpha-2,6-SA specific
neuraminidase (Vibrio cholerae) dose-dependently reduced spheroid volume. OP
enhanced cell aggregation and compaction forming spheroids. PANC1 and MDA-MB231
xenograft tumors from untreated and OP-treated RAGxCgamma double mutant mice
expressed significantly higher levels of alpha-2,3- SA over alpha-2,6-SA. MCF-7
spheroids also expressed a high alpha-2,3-SA to alpha-2,6-SA ratio. These results
suggest that the relative levels of specific sialoglycan structures on the cell
surface correlate with the ability of cancer cells to form avascular
multicellular tumor spheroids and in vivo xenograft tumors.
PMID- 27608846
TI - STA-8666, a novel HSP90 inhibitor/SN-38 drug conjugate, causes complete tumor
regression in preclinical mouse models of pediatric sarcoma.
AB - Long-term survival in patients with metastatic, relapsed, or recurrent Ewing
sarcoma and rhabdomyosarcoma is dismal. Irinotecan, a topoisomerase 1 inhibitor,
has activity in these sarcomas, but due to poor bioavailability of its active
metabolite (SN-38) has had limited clinical efficacy. In this study we have
evaluated the efficacy and toxicity of STA-8666, a novel drug conjugate which
uses an HSP90 inhibitor to facilitate intracellular, tumor-targeted delivery of
the topoisomerase 1 inhibitor SN-38, thus preferentially delivering and
concentrating SN-38 within tumor tissue. We present in vivo evidence from mouse
xenograft models that STA-8666 results in more persistent inhibition of
topoisomerase 1 and prolonged DNA damage compared to irinotecan. This translates
into superior antitumor efficacy and survival in multiple aggressive models of
both diseases in mouse xenografts, as well as in an irinotecan-resistant model of
pediatric osteosarcoma, demonstrated by dramatic tumor shrinkage, durable
remission and prolonged complete regressions following short-term treatment,
compared to conventional irinotecan. Gene expression analysis performed on
xenograft tumors treated with either irinotecan or STA-8666 showed that STA-8666
affected expression of DNA damage and repair genes more robustly than irinotecan.
These results suggest that STA-8666 may be a promising new agent for patients
with pediatric-type sarcoma.
PMID- 27608847
TI - Biological functions of macrophage-derived Wnt5a, and its roles in human
diseases.
AB - Wnt5a is implicated in development and tissue homeostasis by activating beta
catenin-independent pathway. Excessive production of Wnt5a is related to some
human diseases. Macrophage recruitment is a character of inflammation and cancer,
therefore macrophage-derived Wnt5a is supposed to be a player in these
conditions. Actually, macrophage-derived Wnt5a maintains macrophage immune
function, stimulates pro-inflammatory cytokine release, and induces angiogenesis
and lymphangiogenesis. Furthermore, macrophage-derived Wnt5a is involved in
insulin resistance, atherosclerosis and cancer. These findings indicate that
macrophage-derived Wnt5a may be a target in the treatment of these diseases.
Notably, unlike macrophages, the exact role of macrophage-derived Wnt5a in
bacterial infection remains largely unknown.
PMID- 27608850
TI - Coffee-Ring-Free Quantum Dot Thin Film Using Inkjet Printing from a Mixed-Solvent
System on Modified ZnO Transport Layer for Light-Emitting Devices.
AB - Inkjet printing has been considered an available way to achieve large size full
color RGB quantum dots LED display, and the key point is to obtain printed film
with uniform and flat surface profile. In this work, mixed solvent of 20 vol %
1,2-dichlorobenzene (oDCB) with cyclohexylbenzene (CHB) was used to dissolve
green quantum dots (QDs) with CdSe@ZnS/ZnS core/shell structure. Then, by inkjet
printing, a flat dotlike QDs film without the coffee ring was successfully
obtained on polyetherimide (PEI)-modified ZnO layer, and the printed dots array
exhibited great stability and repeatability. Here, adding oDCB into CHB solutions
was used to reduce surface tension, and employing ZnO nanoparticle layer with PEI
modified was used to increase the surface free energy. As a result, a small
contact angle is formed, which leads to the enhancement of evaporation rate, and
then the coffee ring effect was suppressed. The printed dots with flat surface
profile were eventually realized. Moreover, inverted green QD-LEDs with PEI
modified ZnO film as electron transport layer (ETL) and printed green QDs film as
emission layer were successfully fabricated. The QD-LEDs exhibited the maximum
luminance of 12 000 cd/m2 and the peak current efficiency of 4.5 cd/A at
luminance of 1500 cd/m2.
PMID- 27608849
TI - Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and
beta1-integrin in conventional osteosarcoma.
AB - INTRODUCTION: Currently, very few studies are available concerning the mammalian
Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key
downstream effectors of this pathway and may also have oncogenic properties.
Additionally, recent in-vitro experiments showed that expression of beta1
integrin promoted metastasis in osteosarcomas. This study investigated the
expression of YAP/TAZ and beta1-integrin in human osteosarcomas. MATERIALS AND
METHODS: We performed automated immunohistochemistry on tissue-microarrays (TMA)
in which 69 conventional osteosarcomas biopsies performed prior to chemotherapy
were embedded. Cellular localization and semi-quantitative analysis of each
immunostain was performed using Immunoreactive Score (IRS) and correlated to
clinico-pathological data. RESULTS: Cytoplasmic expression of beta1-integrin was
noted in 54/59 osteosarcomas (92%), with 33/59 cases (56%) displaying membranous
staining. YAP/TAZ was expressed in 27/45 osteosarcomas (60%), with 14 cases (31%)
showing cytoplasmic expression while 13 other cases (28%) displayed nuclear
expression. No link was found between YAP/TAZ or beta1-integrin expression and
response to chemotherapy. In univariate analysis, YAP/TAZ immunoreactive score
was pejoratively correlated with overall survival (p = 0.01). Expression of beta1
integrin on cell membrane was also pejorative for OS (p = 0.045). In multivariate
analysis, YAP/TAZ nuclear expression was an independent prognostic factor for PFS
(p = 0.035). CONCLUSION: this study indicates that beta1-integrin and YAP/TAZ
proteins are linked to prognosis and therefore could be therapeutic targets in
conventional osteosarcomas.
PMID- 27608851
TI - A Diagnostic Challenge: Acute Flaccid Paralysis.
PMID- 27608848
TI - Addressing intra-tumoral heterogeneity and therapy resistance.
AB - In the last several years, our appreciation of intra-tumoral heterogeneity has
greatly increased due to accumulating evidence for the co-existence of
genetically and epigenetically divergent cancer cells residing in different
microenvironments within a tumor. Herein, we review recent literature discussing
intra-tumoral heterogeneity in the context of therapy resistance mechanisms at
the genetic, epigenetic and microenvironmental levels. We illustrate the
influence of tumor microenvironment on therapy resistance and epigenetic states
of cancer cells by highlighting the role of cancer stem cells in therapy
resistance. We also summarize different strategies that have been employed to
address various resistance mechanisms at genetic, epigenetic, and
microenvironmental levels in preclinical and clinical studies. We propose that
future personalized cancer therapy design needs to incorporate dynamic and
comprehensive analyses of tumor heterogeneity landscape and multi-dimensional
mechanisms of therapy resistance.
PMID- 27608852
TI - Effects of excess metabolizable protein on ovarian function and circulating amino
acids of beef cows: 1. Excessive supply from corn gluten meal or soybean meal.
AB - In the dairy industry, excess dietary CP is consistently correlated with
decreased conception rates. However, the source from which excess CP is derived
and how it affects reproductive function in beef cattle is largely undefined. The
objective of this experiment was to determine the effects of feeding excess
metabolizable protein (MP) from feedstuffs differing in rumen degradability on
ovulatory follicular dynamics, subsequent corpus luteum (CL) development, steroid
hormone production and circulating amino acids (AA) in beef cows. Non-pregnant,
non-lactating mature beef cows (n=18) were assigned to 1 of 2 isonitrogenous
diets (150% of MP requirements) designed to maintain similar BW and body
condition score (BCS) between treatments. Diets consisted of ad libitum corn
stalks supplemented with corn gluten meal (moderate rumen undegradable protein
(RUP); CGM) or soybean meal (low RUP; SBM). After a 20-day supplement adaptation
period, cows were synchronized for ovulation. After 10 days of synchronization,
gonadotropin releasing hormone (GnRH) was administered to reset ovarian
follicular growth. Starting at GnRH administration and daily thereafter until
spontaneous ovulation, transrectal ultrasonography was used to diagram ovarian
follicular growth, and blood samples were collected for hormone, metabolite and
AA analyses. After 7 days of visual detection of estrus, CL size was determined
via ultrasound. Data were analyzed using the MIXED procedures of SAS. As
designed, cow BW and BCS were not different (P?0.33). Ovulatory follicular
wavelength, antral follicle count, ovulatory follicle size at dominance and
duration of dominance were not different (P>0.13) between treatments. Cows
supplemented with CGM had greater post-dominance ovulatory follicle growth,
larger dominant follicles at spontaneous luteolysis, shorter proestrus, and
larger ovulatory follicles (P?0.03) than SBM cows. No differences (P?0.44) in
peak estradiol, ratio of estradiol to ovulatory follicle volume, or plasma urea
nitrogen were observed. While CL volume and the ratio of progesterone to CL
volume were not affected by treatment (P?0.24), CGM treated cows tended to have
decreased (P=0.07) circulating progesterone 7 days post-estrus compared with SBM
cows. Although total circulating plasma AA concentration did not differ (P=0.70)
between treatments, CGM cows had greater phenylalanine (P=0.03) and tended to
have greater leucine concentrations (P=0.07) than SBM cows. In summary, these
data illustrate that excess MP when supplemented to cows consuming a low quality
forage may differentially impact ovarian function depending on ruminal
degradability of the protein source.
PMID- 27608855
TI - Divergent Reactivity of Nitrocyclopropanes with Huisgen Zwitterions and Facile
Syntheses of 3-Alkoxy Pyrazolines and Pyrazoles.
AB - A novel annulation reaction of trans-2-substituted-3-nitrocyclopropane-1,1
carboxylates with in situ generated Huisgen zwitterions is reported, providing
facile synthesis of 3-alkoxy pyrazolines in good yields and high
diastereoselectivities. This reaction unveils the divergent reactivity of the
nitrocyclopropanes as a kind of versatile donor-acceptor cyclopropanes. It is
also demonstrated that the prepared 3-alkoxy pyrazolines from di-tert-butyl
azodicarboxylate can be readily transformed into the corresponding 3-alkoxy 1H
pyrazoles in moderate yields.
PMID- 27608854
TI - Association between high-risk fertility behaviours and the likelihood of chronic
undernutrition and anaemia among married Bangladeshi women of reproductive age.
AB - OBJECTIVE: To explore the association between high-risk fertility behaviours and
the likelihood of chronic undernutrition, anaemia and the coexistence of anaemia
and undernutrition among women of reproductive age. DESIGN: The 2011 Bangladesh
Demographic and Health Survey, conducted from 8 July to 27 December 2011.
SETTING: Selected urban and rural areas of Bangladesh. SUBJECTS: A total of 2197
ever-married women living with at least one child younger than 5 years. Exposure
was determined from maternal reports of high-risk fertility behaviours. We
considered three parameters, maternal age at the time of delivery, birth order
and birth interval, to define the high-risk fertility behaviours. Chronic
undernutrition, anaemia and the coexistence of anaemia and undernutrition among
women were the outcome variables. RESULTS: A substantial percentage of women were
exposed to have a high-risk fertility pattern (41.8 %); 33.0 % were at single
high-risk and 8.8 % were at multiple high-risk. After adjusting for relevant
covariates, high-risk fertility behaviours were associated with increased
likelihood of chronic undernutrition (adjusted relative risk; 95 % CI: 1.22;
1.03, 1.44), anaemia (1.12; 1.00, 1.25) and the coexistence of anaemia and
undernutrition (1.52; 1.17, 1.98). Furthermore, multiple high-risk fertility
behaviours appeared to have more profound consequences on the outcome measured.
CONCLUSIONS: Maternal high-risk fertility behaviours are shockingly frequent
practices among women in Bangladesh. High-risk fertility behaviours are important
predictors of the increased likelihood of women's chronic undernutrition, anaemia
and the coexistence of anaemia and undernutrition.
PMID- 27608853
TI - Homodimericin A: A Complex Hexacyclic Fungal Metabolite.
AB - Microbes sense and respond to their environment with small molecules, and
discovering these molecules and identifying their functions informs chemistry,
biology, and medicine. As part of a study of molecular exchanges between termite
associated actinobacteria and pathogenic fungi, we uncovered a remarkable fungal
metabolite, homodimericin A, which is strongly upregulated by the bacterial
metabolite bafilomycin C1. Homodimericin A is a hexacyclic polyketide with a
carbon backbone containing eight contiguous stereogenic carbons in a C20
hexacyclic core. Only half of its carbon atoms have an attached hydrogen, which
presented a significant challenge for NMR-based structural analysis. In spite of
its microbial production and rich stereochemistry, homodimericin A occurs
naturally as a racemic mixture. A plausible nonenzymatic reaction cascade leading
from two identical achiral monomers to homodimericin A is presented, and
homodimericin A's formation by this path, a six-electron oxidation, could be a
response to oxidative stress triggered by bafilomycin C1.
PMID- 27608856
TI - The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via
AMPK in high-fat diet-induced ApoE(-/-) mice.
AB - BACKGROUND: Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional
Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.)
Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis
Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular
inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE(-/-))
mice. METHODS: ApoE(-/-) mice that were fed a high-fat diet (HFD) were treated
with DISGT (300 mg/kg/day) or statin (10 mg/kg/day) for 16 weeks. Serum lipid
levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic
lesions and lipid accumulation in the aorta and liver, respectively. The
expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1],
vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase
(FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA
carboxylase (ACC) in the aorta or liver tissues was measured by western blot
analysis. Lipid synthesis and inflammatory responses were assessed by
immunohistochemistry and hematoxylin & eosin staining, respectively. RESULTS:
Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver
weight, and the levels of lipids, including total cholesterol, low-density
lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In
the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of
ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation,
inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC
expression in liver tissues. CONCLUSIONS: The beneficial, anti-lipolytic, and
anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a
result, the expression of inflammatory factors was reduced. Our data provide
evidence that DISGT may have strong therapeutic potential in treating vascular
diseases, such as atherosclerosis.
PMID- 27608857
TI - A synthetic review of notoedres species mites and mange.
AB - Notoedric mange, caused by obligately parasitic sarcoptiform Notoedres mites, is
associated with potentially fatal dermatitis with secondary systemic disease in
small mammals, felids and procyonids among others, as well as an occasional
zoonosis. We describe clinical spectra in non-chiropteran hosts, review risk
factors and summarize ecological and epidemiological studies. The genus is
disproportionately represented on rodents. Disease in felids and procyonids
ranges from very mild to death. Knowledge of the geographical distribution of the
mites is highly inadequate, with focal hot spots known for Notoedres cati in
domestic cats and bobcats. Predisposing genetic and immunological factors are not
known, except that co-infection with other parasites and anticoagulant
rodenticide toxicoses may contribute to severe disease. Treatment of individual
animals is typically successful with macrocytic lactones such as selamectin, but
herd or wildlife population treatment has not been undertaken. Transmission
requires close contact and typically is within a host species. Notoedric mange
can kill half all individuals in a population and regulate host population below
non-diseased density for decades, consistent with frequency-dependent
transmission or spillover from other hosts. Epidemics are increasingly identified
in various hosts, suggesting global change in suitable environmental conditions
or increased reporting bias.
PMID- 27608858
TI - Effect of temperature, relative humidity and rainfall on dengue fever and
leptospirosis infections in Manila, the Philippines.
AB - Dengue fever (DF) and leptospirosis are serious public problems in tropical
regions, especially in Manila, the Philippines. In attempting to understand the
causes of DF and leptospirosis seasonality, meteorological factors have been
suspected, but quantitative correlation between seasonality and meteorological
factors has not been fully investigated. In this study, we investigated
correlation of temporal patterns of reported numbers of laboratory-confirmed
cases of both DF and leptospirosis with meteorological conditions (temperature,
relative humidity, rainfall) in Manila. We used time-series analysis combined
with spectral analysis and the least squares method. A 1-year cycle explained
underlying variations of DF, leptospirosis and meteorological data. There was a
peak of the 1-year cycle in temperature during May, followed by maxima in
rainfall, relative humidity and number of laboratory-confirmed DF and
leptospirosis cases. This result suggests that DF and leptospirosis epidemics are
correlated not only with rainfall but also relative humidity and temperature in
the Philippines. Quantifying the correlation of DF and leptospirosis infections
with meteorological conditions may prove useful in predicting DF and
leptospirosis epidemics, and health services should plan accordingly.
PMID- 27608859
TI - Comparative study of the nutritional quality of potato-wheat steamed and baked
breads made with four potato flour cultivars.
AB - We investigated the nutritional quality of steamed and baked breads containing
35% potato flour from four potato cultivars. Compared with traditional wheat
varieties, potato-wheat steamed and baked breads contained higher dietary fiber
(1.87-fold), K (2.68-fold), vitamin C (28.56-fold), and total polyphenol (1.90
fold) contents and greater antioxidant activity (1.23-fold). Moreover, the
estimated glycemic index of potato-wheat breads ranged from 61.20 (Hongmei-wheat
baked bread) to 67.36 (Atlantic-wheat steamed bread), which was lower than that
of wheat steamed bread (70.22) and baked bread (70.62). In terms of nutritional
value, Hongmei was the optimum cultivar, followed by Blue Congo, Shepody, and
Atlantic. For the same cultivar, the nutritional value of steamed bread was
higher than that of baked bread. In conclusion, potato flour is a potential wheat
flour supplement that improves the nutritional and functional properties of
breads.
PMID- 27608860
TI - Endoscopic Ultrasound: Indian Perspective.
AB - Mediastinoscopy is a minimally invasive surgical procedure that allows
visualization and tissue sampling of mediastinal nodes. Mediastinoscopy has been
extremely valuable in the evaluation and staging of lung cancer and therefore has
been considered the gold standard for this purpose for over 30 years.
Historically, this procedure has been associated with a low morbidity and
mortality and a high sensitivity for diagnosing lung cancer with certain
procedural limitations. Recently, it has been reported that not only is
mediastinoscopy use limited in community practice, concomitant biopsy rates are
limited as well.1 While mediastinoscopy does provide a tissue diagnosis, the
procedure has its limitations. Cervical mediastinoscopy allows access to nodal
stations 2, 3, 4 and 7, leaving out commonly involved pulmonary ligament and
aortopulmonary window nodes.1 It requires general anesthesia and has a morbidity
of 1% and a mortality of 0.2%. The procedure adds considerable expense to the
staging workup. The estimated current cost is $1,700 for the procedure alone and
$7,500 for a mediastinoscopy with a 2-day hospital stay. This prompted the
development of endobronchial ultrasound(EBUS) in the 1990s.2.
PMID- 27608861
TI - Mediastinal Adenopathy in India: Through the Eyes of Endobranchial Ultrasound.
AB - OBJECTIVE: Aetiology of mediastinal adenopathy is likely to vary with geographic
location and socioeconomic status of a population. Whilst most of adenopathy in
the West could be attributed to malignant disorders, causes of the same in a
developing country like India has not been extensively studied earlier due to
lack of less invasive tools to sample these nodes for cytological and
microbiological analysis. Endobronchial ultrasound (EBUS) helps us reach these
nodes as a minimally invasive procedure to take aspirations under real-time
ultrasound guidance. The aim of the present study is to study the aetiology of
mediastinal adenopathy in our population with the help of EBUS. METHODS: This was
a retrospective analysis of all EBUS procedures done by the authors and the
diagnosis thus obtained at Sir Ganga Ram Hospital, New Delhi, India between April
2010 and December 2011. RESULTS: A total of 300 patients underwent EBUS in the
above period. Most common aetiology encountered in our population was a
granulomatous disorder (53% cases) like tuberculosis and sarcoidosis whilst
malignancy was third in order of diagnosis (17% cases). Lymph node enlargement
due to anthracosis was another uncommon aetiology encountered in the study (5%
cases). CONCLUSIONS: Benign granulomatous disorders like tuberculosis and
sarcoidosis are the most common causes of mediastinal adenopathy in our
population. EBUS is proving its worth for diagnosing mediastinal adenopathy.
PMID- 27608863
TI - Study of Association of Atherosclerotic Risk Factors and Metabolic Syndrome in
Patients of Psoriasis at a Tertiary Care Centre in North India: A Case Control
Study.
AB - OBJECTIVE: To study the association between psoriasis and atherosclerotic risk
factors, including metabolic syndrome. METHODS: Fifty patients with psoriasis and
50 controls were included in the study. Atherosclerotic risk factors were
evaluated as per National Cholesterol Education Project Adult Treatment Panel III
(NCEP-ATPIII). Metabolic syndrome was diagnosed as per South Asian Modified
National Cholesterol Education Programme's Adult Treatment Panel III (ATP III).
RESULTS: Psoriatic patients had a significantly higher prevalence of
hypertriglyceridaemia (>=150 mg/dl) (p=0.013), low HDL (< 40mg/dl) (p=0.025),
impaired fasting blood glucose (>=100 mg/dl) (p=0.026). Metabolic syndrome was
present in significant number of psoriasis patients than in controls [42 (28%)
versus 9 (6%)] (P=0.009). CONCLUSIONS: There is a significantly higher prevalence
of metabolic syndrome and atherosclerotic risk factors in psoriasis patients as
compared to controls.
PMID- 27608862
TI - Medical Management and Diagnostic Testing among Stable Angina Patients in India:
The STable Angina obseRvational (STAR) Registry.
AB - OBJECTIVE: To study the practice pattern in the management of patients with
stable angina (SA) in India. METHODS: The Stable Angina obseRvational Registry
(STAR) prospectively enrolled patients provisionally diagnosed with SA by non
interventional practicing internists in India. Patients were followed for 3
months after enrollment to assess medical treatment, diagnostic management, and
interventional treatment of coronary artery disease (CAD). At the study
conclusion, a statistical analysis retrospectively categorized patients not at
risk of CAD by the Morise-Jalisi scale though this was not part of the study
protocol. RESULTS: Between January and May 2012, 2079 patients were enrolled at
131 centres. Mean age was 57 +/- 11 years, 62% were men, and 40% had a history of
diabetes. Over 90% of patients completed follow-up visit, >85% received statins
and antiplatelet medications, >70% received beta blockers, and >60% received
angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers.
Diagnostic testing rates were low: 93% for electrocardiogram, 44% echocardiogram,
42% chest radiography, 12% stress test, and 8% underwent noninvasive CT or
invasive coronary angiography, of which, 86% had abnormal results. After the
study, the Morise-Jalisi probability of CAD was intermediate in 42% and high in
51% of patients. Only 3.4% of all patients had coronary revascularization.
CONCLUSIONS: In a large cohort of Indian patients with SA, disease severity and
probability of CAD were high. Clinicians used evidence-based care for medical
management, but underutilized diagnostic testing. Patients with SA in India need
to be risk-stratified for probability and severity of CAD and, if indicated,
receive additional diagnostic testing.
PMID- 27608864
TI - Thrombophilia Profile in Budd-Chiari Syndrome and Splanchnic Vein Thrombosis: A
Study from Western India.
AB - AIM: To estimate the prevalence of inherited prothrombotic risk factors in
patients with splanchnic venous thrombosis (SVT) and Budd-Chiari syndrome (BCS)
and to compare the risk factor profiles between these two groups. METHODS: In
this prospective study, patients with abdominal venous thrombosis were studied.
The patients were divided into two groups on the basis of the veins involved;
splanchnic venous thrombosis group [portal (PVT), splenic, superior mesenteric
veins (SMV)] and Budd-Chiari group (hepatic vein, IVC thrombosis). Thrombophilia
profile including protein C, protein S, antithrombin III, factor V Leiden
mutation, activated protein C, factor VIII level, CD55, CD59, IgM cardiolipin,
IgG cardiolipin, anti-beta2 glycoprotein, JAK2 mutation, homocysteine levels,
MTHFR and lupus anticoagulant was done in all patients. RESULTS: Out of 30
patients, 23 patients had SVT, 7 had BCS, including 2 of the 23 patients with SVT
had mixed venous thrombosis, PVT and SMV thrombosis. Risk factors were found in
21/30 (70%) patients [17/23 (73.9%) of PVT. 4/7 (57.1% of BCS] and multiple risk
factors were overall present in 8/23(34.7%) patients of SVT. CONCLUSIONS:
Hereditary risk factors play an important role in the etiopathogenesis of
abdominal venous thrombosis and hyperhomocysteinemia and protein S deficiency are
the most common risk factors.
PMID- 27608865
TI - Asthma Insights and Management in India: Lessons Learnt from the Asia Pacific -
Asthma Insights and Management (AP-AIM) Study.
AB - BACKGROUND: Despite a better understanding of the pathophysiology of asthma,
presence of reliable diagnostic tools, availability of a wide array of effective
and affordable inhaled drugs and simplified national and international asthma
management guidelines, asthma remains poorly managed in India. OBJECTIVE: The
Asia-Pacific Asthma Insight and Management (AP-AIM) study was aimed at
understanding the characteristics of asthma, current management, level of asthma
control and its impact on quality of life across Australia, China, Hong Kong,
India, Malaysia, Singapore, South Korea, Taiwan and Thailand. This paper
describes the results of asthma management issues in India in detail and provides
a unique insight into asthma in India. METHODOLOGY: The AP-AIM India study was
conducted in eight urban cities in India, viz: Ajmer, Delhi, Kolkata, Rourkela,
Chennai, Mangalore, Mumbai and Rajkot from February to July 2011. Face-to-face
interviews were conducted in adult asthmatics and parents of asthmatic children
between the ages of 12 and 17 years with a confirmed diagnosis or a treatment
history of 1 year for asthma. RESULTS: Four hundred asthmatics (M:F::1:1.273),
with a mean age of 50 +/- 17.8 years, from across India were studied. 91% of the
asthmatics in India perceived their asthma to be under control, however, none of
the asthmatics had controlled asthma by objective measures. Asthmatics in India
believed that their asthma was under control if they have up to 2 emergency
doctor visits a year. The quality of life of these patients was significantly
affected with 93% school/work absenteeism and a loss of 50% productivity. Seventy
five percent of the asthmatics have never had a lung function test. The common
triggers for asthmatics in India were dust (49%) and air pollution (49%), while
only 5% reported of pollen as triggers. Eighty-nine percent of Indian asthmatics
reported an average use of oral steroids 10.5 times a year. Only 36% and 50% of
Indian asthmatics used controller and rescue inhalers with a majority preferring
the oral route of asthma medication. CONCLUSIONS: This study has clearly
highlighted the fact that asthma management in India remains very poor, with a
significant proportion of patients experiencing bothersome symptoms and worsened
quality of life. There is a need for an urgent review of this situation and
initiate active measures at local as well as national levels to improve asthma
care in India.
PMID- 27608866
TI - Results: Unraveling the Findings.
AB - Results section is used to inform readers about the actual observations made in
the research study. The authors should ensure that the content is appropriate,
complete and objective. Using tables and graphs appropriately enhances the
readers' interest and understanding.
PMID- 27608867
TI - Approach to Chronic Lymphocytic Meningitis.
AB - Chronic meningitis is a common clinical problem. Early diagnosis and appropriate
therapy is important in improving the overall outcome and to prevent long-lasting
sequels. As many etiological agents lead to the development of chronic
lymphocytic meningitis, it is important to develop a systematic approach to the
diagnosis; taking clues from history, examination and laboratory tests, to make
an accurate diagnosis and institute appropriate therapy. This review focuses on
the diagnostic approach towards the commonly encountered situation of chronic
lymphocytic meningitis. Chronic meningitis is defined as meningeal inflammation
that persists for more than 4 weeks. Chronic meningitis accounts for less than
10% of all the cases of meningitis.1 Causes of chronic lymphocytic meningitis are
mainly divided into infectious and non-infectious listed in Table 1.2 Due to
advancement in investigations, diseases causing chronic meningitis may be
diagnosed earlier than 4 weeks and hence the definition should be considered as a
rough guideline.
PMID- 27608869
TI - Right Atrial Myxoma.
AB - A 54 yr old man, non-smoker, non-alcoholic, and non-diabetic, non-hypertensive,
non-obese, with moderate daily activity and no significant past medical history,
presented with chief complaints of dyspnoea NYHA Class III, which was associated
with diaphoresis and restlessness. On examination, a long systolic murmur of
grade III-IV, increasing on inspiration, was audible in the tricuspid area. The
murmur did not have any postural relation. An abnormal thud-like sound was
audible in left parasternal region. There was no evidence of any pleuro
pericardial rub. Transthoracic echocardiography showed a large (7*4 cm), mobile
mass arising in the right atrium superiorly, prolapsing through tricuspid valve,
into the right ventricle, resulting in moderate tricuspid regurgitation. 2D echo
(Figure 1) and cardiac MRI (Figure 2) of the heart showed a isointense to mildly
hypointense mass from the right atrium prolapsing through the tricuspid valves
into the right ventricle on T2 weighted images. There was abscence of any
enhancement of the mass after administration of IV gadolinium. The patient
underwent excision of the myxoma. Histopathological examination showed a tumour
with extensive myxomatous matrix with dispersed cellular components. The tumour
cells were arranged in single or multiple layers surrounding vascular channels,
which were lined by endothelium. The tumour cells had spindle-shaped nuclei with
occasionaly vacuolated eosinophilic cytoplasm. There was no increase in mitosis.
In addition there was background of lympho-plasmacytic infiltrate (Figure 3). The
patient remained asymptomatic for the period of one and a half years of follow up
post-operatively.
PMID- 27608868
TI - Epidemiology and Genetics of Hypertension.
AB - The prevalence of hypertension is increasing in India as well as in the world.
The average prevalence of hypertension in India is 25-30%. The median prevalence
of total hypertension in 2009 was 37.6% in men and 40.1% in women in U.S.
Hypertension is a major risk factor for majority of patients with cardiovascular,
cerebrovascular and renal morbidity and mortality. Environmental factors as well
as genetic factors account for regulation of blood pressure and its control.
Understanding of genetic factor may not only help in recognising those at risk
but also help in treatment. Discovering hypertension susceptibility genes would
help recognizing those at risk for developing the disease before the expression
of clinical symptoms. Genetic and epidemiological studies have suggested that
essential hypertension is a polygenic and multifactorial disorder that results
from genetic and/or environmental factors. In India awareness, treatment and
control status of hypertension is low, with only half of the urban and a quarter
of the rural hypertensive individuals being aware of its presence. In this review
we have discussed epidemiology and genetics of hypertension, both the monogenic
and polygenic forms.
PMID- 27608870
TI - Salt and Pepper Pigmentation - Skin Manifestation of Systemic Sclerosis.
AB - A 50 year old male presented with progressive difficulty in swallowing both
liquid and solid food with no history of Raynaud's phenomenon. A general
examination revealed skin changes in the form of thickening, hyperpigmentation
and tightening of skin of fingers, hand, forearm and legs. The patient had
painless skin induration over the legs, forearm and hand. Salt and pepper
pigmentation was seen on the upper back (Figure 1a), over mastoid process (Figure
1b) and the concha of pinna (Figure 1c). Anti-Scl 70 was positive. Anti
centromere antibodies were negative. Pulmonary function testing (PFT) revealed
very severe restrictive lung disease. Barium swallow study was normal. Despite
being advised to undergo oesophageal manometry test in view of dysphagia, patient
was not willing for the same. Diagnosis of systemic sclerosis was made. Systemic
sclerosis is a disease in which extensive fibrosis, vascular alterations and
autoantibodies against various cellular antigens being the principal features
with a female to male ratio of 4:1. Skin pigmentation changes among other
features of skin involvement include a salt-and-pepper appearance due to diffuse
hyperpigmentation with sparing of the perifollicular areas. This may be due to
the richer capillary network that may warm the perifollicular skin and preserve
melanogenesis producing the perifollicular pigment retention in systemic
sclerosis.1,2 Both cellular and humoral immune factors in combination with
external factors such as trauma or inflammation may trigger the destruction of
melanocytes.3 Moreover, various physical factors like temperature changes as well
as genetic, hormonal factors may influence pigment formation. Such changes in
pigmentation is also seen during repigmentation around hair follicles in
vitiligo. Clinically, both vitiligo and depigmented lesions of systemic sclerosis
present as chalk-white macules with well-defined borders. However, mucosal
involvement is commonly seen in vitiligo while depigmented lesions are usually
not observed involving the lips or oral cavity in systemic sclerosis.
PMID- 27608871
TI - Laryngeal Leishmaniasis with Extra-pulmonary Tuberculosis.
AB - Clinical presentations of Leishmania infection include visceral (most common
form), cutaneous, mucocutaneous, mucosal and post-kala-azar dermal leishmaniasis.
Mucosal form of leishmaniasis mostly involves oral and nasal mucosa. Rarely,
laryngeal and pharyngeal mucosa may also be involved. Its concomitant presence
with tuberculosis (TB), a disease rampant in India, is uncommon. Here we are
reporting a case of isolated laryngeal leishmaniasis associated with extra
pulmonary tuberculosis (EPTB), with approach to diagnosis and treatment in a
tropical resource-limited setting.
PMID- 27608872
TI - Transient Trifascicular Block in Severe Hyperkalemia.
AB - Hyperkalemia is a commonly encountered electrolyte abnormality that can
significantly alter normal cardiac conduction. Potentially lethal dysrhythmias
associated with hyperkalemia include complete heart block and Mobitz Type II
second-degree AV block. We report a case of trifascicular block, due to
hyperkalemia. The patient's symptoms and electrocardiogram (ECG) evidence of
trifascicular block resolved with lowering of serum potassium levels, with
subsequent ECG showing left anterior hemiblock. This paper highlights an
infrequently reported dysrhythmia associated with hyperkalemia that emergency
physicians should be familiar with.
PMID- 27608873
TI - Atrial Septal Aneurysm Presenting as Clubbing without Clinically Apparent
Cyanosis.
AB - Atrial septal aneurysm (ASA) is a localised "saccular" deformity which protrudes
to the right or the left atrium or on both sides. It is a rare, but well
recognised cardiac abnormality. It is usually an incidental finding or may
presents as atrial arrhythmias or arterial embolism. Though it is an acyanotic
congenital heart disease but it may result in significant right to left shunt and
cyanosis. We describe a patient of ASA with atrial septal defect who presented
with clubbing and right to left shunt without clinically apparent cyanosis.
PMID- 27608874
TI - Urinary Ascites - A Consequence of Intraoperative Injury.
AB - Patients with complications after surgery often pose enormous challenges to
physicians. We report the case of a young lady developing fever, oliguria and
intractable ascites refererred to us after undergoing abdominal surgery. She was
diagnosed subsequently to have a urinoma with urinary ascites masquerading as a
case of sepsis. Percutaneous nephrostomy followed by definitive repair and
reimplantation of ureter later led to subsidence of the symptoms.
PMID- 27608875
TI - Acquired Bartter-Like Phenotype.
AB - We present a case of middle-aged man who presented with sudden onset of weakness
of both upper and lower limbs with hypotension and polyuria without any
antecedent illness. Investigations showed severe hypokalemia, hypocalcemia,
hyponatremia, mild hypomagnesemia, hypercalciuria, metabolic alkalosis and
increased renin and aldosterone levels in the blood suggesting Bartter syndrome.
Thus a diagnosis of acquired Bartter-like phenotype was made.
PMID- 27608876
TI - Non-Functional Adrenal Gland Ganglioneuroma Masquerading as Chronic Calculus
Cholecystitis.
AB - Adrenal ganglioneuromas in young adults are rare and ill-understood. We report an
incidentally detected adrenal gland tumor diagnosed as ganglioneuroma (mature
type) in 33 years old man who presented with vomiting and epigastric pain for 2
months. Histopathology examination revealed a well-encapsulated benign tumor of
mature ganglion cells and Schwann-like cells arranged in fascicles, staining
strongly with NSE and s-100 proteins, with adjacent unremarkable adrenal cortex
and medulla.
PMID- 27608877
TI - Anorexia Nervosa with Obsessive-Compulsive Disorder.
AB - We report the case of an adolescent female, previously nonobese, belonging to
educated average socioeconomic Muslim family. She stopped taking food, developed
a perception of distorted body image with occasional episodes of binge eating and
forced vomiting. She became amenorrheic and emaciated with loss of secondary
sexual characters. She satisfied the criteria for anorexia nervosa with obsessive
compulsive disorder.
PMID- 27608878
TI - Hashimoto's Encephalopathy Presenting with Chorea.
AB - Hashimoto's encephalopathy (HE) is a steroid-responsive relapsing
neuropsychiatric disorder associated with high titers of antithyroid antibody
with or without thyroid dysfunction. We report a case of HE in a 78 year old
female who developed sudden onset behavioral abnormalities associated with
choreiform movement of extremities. All causes of vascular, infective, metabolic,
autoimmune, paraneoplastic and toxic encephalopathy were excluded. Anti-thyroid
peroxidase (anti-TPO) antibody was found to be raised with very high titre. A
diagnosis of HE was made. Prompt treatment with high dose steroid led to dramatic
improvement of symptoms including choreiform movement.
PMID- 27608879
TI - Systemic Lupus Erythematosus with Deep Vein Thrombosis and Cutaneous Ulcer.
AB - We are reporting a case of systemic lupus erythematosus (SLE) with left upper
limb and lower limb deep vein thrombosis (DVT) due to protein S deficiency which
was aggravated by anticoagulants. Oral anticoagulant-induced skin necrosis also
developed in this patient. This patient was negative for anti-phospholipid
antibodies (APLA). Such a case is rarity where SLE patient without APLA has
protein S deficiency.
PMID- 27608880
TI - Acute Onset Sensory Polyneuropathy Due to Metronidazole Therapy.
AB - Metronidazole is associated with numerous neurologic complications, including
peripheral neuropathy particularly in patients; those are on high doses of
metronidazole for prolonged period. We hereby report a case of liver abscess that
developed sensory polyneuropathy following 11 days of metronidazole therapy at
low cumulative dose.
PMID- 27608881
TI - Pioneers in Antimicrobial Chemotherapy.
AB - "If we are not careful, we soon will be in the post-antibiotic era, and for some
patients and some microbes we are already there"- Tom Friedan Antibiotics
revolutionized medicine in the 20th century. The era of antibacterial
chemotherapy began in 1907 with the discovery of arsphenamine, first synthesized
by Alferd Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first
systemically active antibiotic, Prontosil was discovered in 1933 by Gerhard
Domagk, for which he was awarded the 1939 Nobel Prize. Fleming's accidental
discovery and isolation of penicillin in September 1928 marked the start of
modern antibiotics. It was a discovery that changed the course of history and
saved millions of lives.
PMID- 27608882
TI - Adam Politzer-Father of Modern Otology.
AB - Adam Politzer (1835-1920) was born in Alberti near the city of Budapest in
Hungary. He studied medicine at the University of Vienna and obtained his
Doctorate degree in 1859. Some of his teachers belonged to the famous second
"Vienna School" such as Joseph Skoda, Karl Rokitansky, Von Hebra, Josef Hyrtil,
Johann Von Oppolzer and famous physiologist Carl Ludwig -who took special
interest in him and was influential in his subsequent career. Politzer showed
unusual interest in diseases of the ear and started to work in Carl Ludwig's
laboratory. His interest at that time was mainly the physics of the auditory
system. He studied the innervations of the intrinsic muscles of the ear There he
was the first to demonstrate that the innervations of the tensor tympani muscle
was by trigeminal nerve and that of the stapedial muscle was by facial nerve. He
studied the air movement in the Eustachian tube and variation of air pressure in
the tympanic cavity by connecting two manometers- one placed in the external
auditory canal meatus, and another in the pharynx. He showed valve near the
opening into the middle ear which controls the process. It is usually closed to
keep the bacteria and other things away from the mouth and nose.
PMID- 27608883
TI - Asymptomatic Unilateral Hyperlucent Lung in a Prospective Kidney Donor.
AB - A 50 year old lady, prospective kidney donor was referred to our department for
opinion in view of abnormal clinical findings during preoperative evaluation. She
was asymptomatic from respiratory point of view. Her vital parameters were normal
and on auscultation found to have decreased breath sounds and fine crackles
throughout left hemithorax. Chest x-ray (CXR) showed left sided hyperlucency with
small hilum (Figure 1). High resolution computed tomography (HRCT) showed
scattered areas of bronchiectasis with associated air trapping throughout left
lung with small left pulmonary artery (Figure 2). Sputum for acid fast bacilli
(AFB) was negative. Spirometry showed moderate obstructive abnormality with
forced expiratory volume in one second (FEV1) - 51% predicted, forced vital
capacity (FVC) - 60% and FEV1/FVC - 76% with no bronchodilator reversibility. On
post bronchodilator study there was paradoxical fall in FEV1/FVC to 72%
consistent with small airway disease. Arterial blood gas analysis was normal.
Technetium (Tc) 99m MAA lung perfusion scan (Figure3) showed normal perfusion of
right lung contributing 75.4% of relative function and left lung contributing
only 24.6%. Diagnosis of Swyer-James-MacLeod syndrome (SJMS) probably due to a
childhood viral infection was made. Operative complications in such cases like
difficult weaning and extubation, post-operative respiratory infections, collapse
and respiratory failure are likely. However, our patient had an uneventful
operative and post-operative course. SJMS is characterized by unilateral
hyperlucency of a part of or the entire lung which was first described in 1953 by
Swyer and James and later in 1954 by Macleod.1,2 It is considered to be an
acquired disease as a result of post-infectious obliterative bronchiolitis.
Productive cough, shortness of breath and sometimes hemoptysis are presenting
symptoms. Some patients are asymptomatic and not diagnosed until they are
adults.3 Radiologically it presents as predominant unilateral hyperlucency. Hence
other causes of unilateral hyperlucent lung like pneumothorax, idiopathic giant
bullae, congenital lobar emphysema, pulmonary artery hypoplasia, pulmonary
embolism and bronchial obstruction due to foreign body or mucus plugs should be
considered. Treatment is supportive with early control of super-added infections
along with influenza and pneumococcal vaccination. Bronchodilators can be useful,
especially if the spirometry shows obstructive abnormality.
PMID- 27608884
TI - Dyke-Davidoff-Masson Syndrome: Time to Revisit Case Series.
AB - We read a case report by Manghera et al (JAPI, Vol 62 page No. 76-67), which was
in response to an earlier case report by Ola et al.1 Here we would like to share
our experience and views as under- The authors in the correspondence have said
that crossed cerebellar atrophy is an unusual and rare finding. We in our study
of 28 patients of DDMS, have found cerebellar atrophy in nine patients along with
cerebral atrophy.2 Out of nine patients with cerebellar atrophy three patients
had diffuse bilateral atrophy, only one patient had unilateral cerebellar atrophy
which was controlateral to left cerebral hemiatrophy (CHA). This is similar to
the findings of the authors and the patho-physiology quoted by authors is worth
appreciation. Other parenchymal changes observed in our study were cerebral
peduncle atrophy in three patients, and thalamic atrophy with lentiform nucleus
hypoplasia in 11 patients. Seven cases of CHA were associated with ipsilateral
large schizencephalic cleft with absence of the septum pellucidum whereas two had
porencephaly. Five patients had left-sided hippocampal sclerosis (HS), four were
concordant and one was discordant.
PMID- 27608886
TI - On the development of multifunctional luminescent supramolecular hydrogel of gold
and egg white.
AB - Highly stable, luminescent, and printable/paintable supramolecular egg white
hydrogel-based surface enhanced Raman scattering (SERS) matrix is created by an
in situ synthesis of gold clusters inside a luminescent egg white hydrogel (Au
Gel). The synthesis of stable luminescent egg-white-based hydrogel, where the
hydrogel can act as a three dimensional (3D) matrix, using a simple cross-linking
chemistry, has promising application in the biomedical field including in 3D cell
culturing. Furthermore, this functional hydrogel is demonstrated for micromolar
level detection of Rhodamine 6G using the SERS technique, where Au-Gel is painted
over a flexible cellulose pad.
PMID- 27608887
TI - [Formula: see text]Executive functioning and its relation to ASD and ADHD
symptomatology in 22q11.2 deletion syndrome.
AB - Children with 22q11.2 deletion syndrome (22q11DS; velo-cardio-facial-syndrome)
are at risk for the developmental disorders, attention deficit hyperactivity
disorder (ADHD) and autism spectrum disorder (ASD). In this study, the relation
between executive functioning (EF) and the severity of ADHD and ASD symptoms is
examined, since EF is known to be important in relation to emotional and
behavioral problems. The participants consist of 58 children (38 females) with a
mean age of 13.5 years (SD 2.6). Standardized assessment was used to evaluate the
severity of ASD and ADHD symptomatology. The major aspects of EF, i.e., cognitive
flexibility, inhibition, sustained attention, distractibility, working memory and
reaction speed, were evaluated. The profile of EF in 22q11DS was found to be
characterized by weaker performance compared to the norms on all subdomains of
EF. Poor cognitive flexibility and inhibition, as well as high distractibility,
were found to be related to more severe ASD symptoms, while poor quality of
sustained attention and high distractibility were found to be related to more
severe ADHD symptoms. It is concluded that children with 22q11DS experience
impairments in EF, and that the degree of impairment on specific EF subdomains is
related to the severity of ASD and/or ADHD symptomatology. These results may help
in defining the mediating role of neurocognitive dysfunctions in the development
of social and behavioral problems in 22q11DS.
PMID- 27608885
TI - Stabilized Collagen and Elastin-Based Scaffolds for Mitral Valve Tissue
Engineering.
AB - There is a significant clinical need for new approaches to treatment of mitral
valve disease. The aim of this study was to develop a tissue-engineered mitral
valve scaffold possessing appropriate composition and structure to ensure ideal
characteristics of mitral valves, such as large orifice, rapid opening and
closure, maintenance of mitral annulus-papillary muscle continuity, in vivo
biocompatibility and extended durability. An extracellular matrix-based scaffold
was generated, based on the native porcine mitral valve as starting material and
a technique for porcine cell removal without causing damage to the matrix
components. To stabilize these structures and slow down their degradation,
acellular scaffolds were treated with penta-galloyl glucose (PGG), a well
characterized polyphenol with high affinity for collagen and elastin. Biaxial
mechanical testing presented similar characteristics for the PGG-treated
scaffolds compared to fresh tissues. The extracellular matrix components, crucial
for maintaining the valve shape and function, were well preserved in leaflets,
and in chordae, as shown by their resistance to collagenase and elastin. When
extracted with strong detergents, the PGG-treated scaffolds released a reduced
amount of soluble matrix peptides, compared to untreated scaffolds; this
correlated with diminished activation of fibroblasts seeded on scaffolds treated
with PGG. Cell-seeded scaffolds conditioned for 5 weeks in a valve bioreactor
showed good cell viability. Finally, rat subdermal implantation studies showed
that PGG-treated mitral valve scaffolds were biocompatible, nonimmunogenic,
noninflammatory, and noncalcifying. In conclusion, a biocompatible mitral valve
scaffold was developed, which preserved the biochemical composition and
structural integrity of the valve, essential for its highly dynamic mechanical
demands, and its biologic durability.
PMID- 27608888
TI - miRNA-15a-5p regulates VEGFA in endometrial mesenchymal stem cells and
contributes to the pathogenesis of endometriosis.
AB - OBJECTIVE: miRNAs have been recently reported to contribute to the etiology of
endometriosis in stem cells. However, the mechanisms remain unclear. The aim of
this investigation is to explore the expression of miR-15a-5p and VEGFA in
endometrial samples from patients with or without endometriosis. And then examine
the regulation by miR-15a-5p on the expression of VEGFA. PATIENTS AND METHODS:
Here we collected 31 endometrial samples from patients with or without
endometriosis and characterized the miRNAs expression profiles of these two
groups. Then, we investigated the regulation by microRNA-15a-5p (miR-15a-5p) on
the expression of vascular endothelial growth factor (VEGF) in endometrial
mesenchymal stem cells. RESULTS: It was demonstrated that there was dramatically
down-regulation of miR-15a-5p in the patients with endometriosis, compared with
control patients. Moreover, we found that the up-regulation of miR-15a-5p
suppressed cell proliferation, migration and invasion of these ectopic stem cells
by targeting the 3' untranslated region of VEGFA. CONCLUSIONS: Taken together,
this newly identified miR-15a-5p module provides a new avenue to the
understanding of the processes of endometriosis development, especially
proliferation, motility as well as angiogenesis, and may facilitate the
development of potential therapeutics against endometriosis.
PMID- 27608889
TI - Effects of LeY glycan expression on embryo implantation.
AB - OBJECTIVE: To investigate the correlation between LeY glycan expression and
embryo implantation. MATERIALS AND METHODS: Uterine epithelial cells before
implantation were transfected with FUT1siRNA to inhibit FUT1 (the gene encoding
the key enzyme of LeY synthesis) expression and treated with 10 ng/ml leukemia
inhibitory factor (LIF). Murine embryo implantation model in vitro was prepared
by late blastocysts with identical morphology and treated uterine epithelial
cells co-culture. Using RT-PCR, dot blot and observation of embryo attachment to
analyze FUT1 gene expression and LeY synthesis of uterine epithelial cells and
studied further the correlation of LeY expression level and embryo implantation.
RESULTS: FUT1 gene expression and LeY synthesis declined after cells were
transfected with FUT1siRNA, and LIF promoted FUT1 expression and LeY synthesis.
After expression of FUT1 gene was inhibited, attachment rate of embryos lowered,
but LIF up-regulated FUT1 expression and increased the attachment rate of
embryos. CONCLUSIONS: These results indicated regulating FUT1 expression affected
LeY synthesis, and then LeY regulated the recognition and attachment of uterus
embryo and participates in embryo implantation further.
PMID- 27608890
TI - Alterations of the vaginal microbiota in the third trimester of pregnancy and
pPROM.
AB - OBJECTIVE: Preterm premature rupture of membranes (pPROM) is a significant issue
in obstetric practice. One of the risk factors for pPROM are vaginal infections
in the third trimester of pregnancy. PATIENTS AND METHODS: We performed an
observational study on 600 pregnant women, analyzing the lactobacillary grade
(LBG) and the presence of any pathogenic bacteria and/or Candida at weeks 28 and
32 of pregnancy and recording any pPROM events at delivery. At week 28, in the
case of vaginal infection, the patients were treated for 6 days with a topical
association of metronidazole+clotrimazole. RESULTS: At week 28 of pregnancy 54.2%
of women had vaginal infection (32.6% bacterial vaginitis, 33.8% candidiasis and
32.4% mixed infection) and/or abnormal vaginal microbiota (67.4% LBG 2a/2b, 32.6%
LBG 3). The total number of pPROM was 8 out of 600 (1.3%). The treatment of
vaginal infection at week 28 with the topical association of
metronidazole+clotrimazole, led to both the eradication of vaginal infections and
the restoration of the vaginal microbiota in 72% of the cases, bringing the level
of risk of pPROM similar to that of women without vaginal infection at week 28.
In addition, the results showed that women with vaginal infections and/or
alteration of vaginal microbiota at week 32 of pregnancy had a higher prevalence
of pPROM in comparison to the women without vaginal infection at week 32
(p<0.001). CONCLUSIONS: This observational study showed the high prevalence of
vaginal infections in the third trimester of pregnancy and its association with
pPROM. Furthermore, data suggested the possible benefits of the topical treatment
with metronidazole+clotrimazole in pregnancy to eradicate infections, restore the
normal microbiota and reduce the risk of pPROM.
PMID- 27608891
TI - Preliminary study on diagnosis of lumbar disc degeneration with magnetic
resonance T1p, T2 mapping and DWI quantitative detection technologies.
AB - OBJECTIVE: The value of diagnosing lumbar disc degeneration with T1p magnetic
resonance imaging (MRI), T2 mapping and diffusion-weighted imaging (DWI)
technologies. PATIENTS AND METHODS: We selected 30 patients diagnosed with lumbar
disc herniation (group A), 30 patients with lumbar disc degeneration (group B)
and 30 healthy volunteers (group C) and carried out Pfirrmann grading of
intervertebral discs (L1-S1 segment) based on conventional T2WI median sagittal
images. T1p, T2 mapping and DWI were then applied. RESULTS: Group A primarily had
Pfirrmann grades of III-IV, group B had Pfirrmann grades of I-IV and group C had
Pfirmann grades of I-II. The differences between the groups were statistically
significant (p <0.05). The average T1p, T2 mapping and apparent diffusion
coefficient (ADC) values of the nucleus pulposus and annulus fibrosus in group A
were significantly lower than in group B. The highest values were in group C, and
the differences were statistically significant (p <0.05). CONCLUSIONS: T2WI, T1p
MRI, T2 Mapping and DWI technologies have different capacities to diagnose lumbar
disc degeneration, and have great value in improving diagnostic accuracy.
PMID- 27608892
TI - Age and gender related changes in bronchial tree: a morphometric study with
multidedector CT.
AB - OBJECTIVE: The aims of this study are the identification of differences in the
diameter, length, area and branching angles of the trachea and bronchi with
gender and age, and the identification of trachea types by using MDCT images.
PATIENTS AND METHODS: The thoracic MDCT images of 253 patients (0-74 years old,
142 male and 111 female) were evaluated. Tracheal diameter, tracheal cross
sectional area, diameter and length of bronchi, and several angles of the
bronchial tree [e.g. subcarinal angles (SCA), interbronchial angles (IBA)] were
measured. RESULTS: Average anteroposterior and transverse diameter of the trachea
in adult patients were measured as 15.8 +/- 2.9 mm and 17.5 +/- 3.7 mm
respectively. Average tracheal cross-sectional areas in adult patients were
calculated as 160.7 +/- 41.3 mm2 in females and as 275.7 +/- 57.3 mm2 in males.
Four types of trachea were identified as circular (68% in adults, 73% in
children), oval (13%, 15%), rectangular (11%, 5%) and horseshoe shaped (8%, 7%).
The average right and left SCA were calculated as 34.5o +/- 8.1o and 38.1o +/-
8.9o respectively. The average right and left IBA were calculated as 32.4o +/-
7.7o and 35.2o +/- 8.1o respectively. CONCLUSIONS: The findings of this study may
be helpful during bronchoscopy and tube and stent application procedures. MDCT
seems to be a convenient technique for the evaluation of the bronchial tree.
PMID- 27608893
TI - Correlation of multiple proteins with clinic-pathological features and its
prognostic significance in colorectal cancer with signet-ring cell component.
AB - OBJECTIVE: Primary colorectal cancer (CRC) with signet-ring cell (SRC) component
is a distinct tumor of colon and rectum, and its prognosis is very poor. Reliable
markers to predict the poor clinical outcome of this subgroup cancer remains
undetermined. Therefore, we perform this study to investigate the prognosis value
of seven proteins in CRC with SRC component . PATIENTS AND METHODS: This study
involved 117 patients diagnosed with CRC with SRC component between January 2008
and August 2015 at Fudan University Shanghai Cancer Center. The samples from
these patients were analyzed by immunohistochemistry to reveal the expression
levels of p53, p21, E-cadherin, COX-2 (Cyclo-oxygenase-2), Bcl-2, CD44 and Ki-67.
Kaplan-Meier analysis and log-rank testing were performed to estimate survival.
Subsequently, a Cox proportional hazard model was used to calculate hazard ratios
for the risk of death. RESULTS: The p21, p53, COX-2, E-cadherin, Bcl-2, CD44 and
Ki-67 expression were detected in 60.5%, 61.3%, 69.7%, 68%, 28.6%, 62.2% and
75.6% of the samples, respectively. The positive expression of p53 (p=0.017) and
the negative expression of COX-2 (p=0.001) or E-cadherin (p=0.047) in CRC with
SRC component were significantly associated with decreased overall survival, but
the other expression levels were not. In a multivariate analysis, the negative
expression of COX-2 was found to be an independent prognostic factor for poorer
overall survival (hazard ratio, 0.37; 95% confidence interval, 0.19 to 0.75,
p=0.003) CONCLUSIONS: The COX-2 positive expression in CRC patients with SRC
component had a poorer outcome than patients who were COX-2-negative. Therefore,
COX-2 could be considered as an indicator for appropriate treatment and intensive
follow-up in these subgroup patients.
PMID- 27608894
TI - Comparative study on long-term survival results between minimally invasive
surgery and traditional resection for esophageal squamous cell carcinoma.
AB - OBJECTIVE: To investigate the long-term survival between minimally invasive
surgery and traditional resection in the treatment of stage I esophageal squamous
cell carcinoma. PATIENTS AND METHODS: 240 patients with esophageal squamous cell
carcinoma were divided randomly into the study group (120 cases) treated by
minimally invasive surgery and the control group (120 cases) treated by
traditional resection. Patients were followed-up by phone or visiting, and were
observed for survival rates, complications and quality of life. RESULTS: The
study group survival rates of one, three and five years are 92.6%, 88.5% and
67.6%, respectively. The control group survival rates of one, three and five
years are 87.1%, 76.3% and 52.5%, respectively, and the difference was
statistically significant (p<0.01). The post-operative complication rate was
12.5% in the study group and 33.3% in the control group and the difference was
statistically significant (p<0.05). Furthermore, the post-operative quality of
life of patients in the study group are improved. 96.7% (116/120) are above 70 in
Karnofsky score, with most surviving patients living independently, and having
lighter self-reported symptoms. 81.7% (98/120) of patients in the control group
are above 70 in Karnofsky score, and the Karnofsky score of post-operative
quality of life between the two groups is statistically significant (p<0.05).
CONCLUSIONS: Compared with traditional resection, minimally invasive surgery is
advantageous in improving both survival rates and quality of life, and is thereby
worthy of clinical promotion and application.
PMID- 27608895
TI - Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian
cancer.
AB - OBJECTIVE: The purpose of the present study was to examine the expression levels
of lncRNA NEAT1 in fresh ovarian cancer (OC) tissue and matched adjacent normal
tissue specimens, and investigate the clinical significance of NEAT1 in OC.
PATIENTS AND METHODS: NEAT1 levels in OC tissues and matched adjacent normal
tissue specimens were tested by qRT-PCR. Then, statistical analysis was performed
to explore the associations of NEAT1 expression with the clinical features and
the prognosis of OC. RESULTS: NEAT1 is upregulated in ovarian cancer tissues
compared with the corresponding adjacent non-neoplastic tissues. The expression
level of NEAT1 was positively correlated with FIGO stage (p = 0.004), tumor grade
(p = 0.009) and distant metastasis (p = 0.000). Also, the Kaplan-Meier survival
curves revealed that high NEAT1 expression was associated with poor prognosis in
OC patients. Multivariate Cox regression analysis showed that NEAT1 expression
level (p < 0.001) was an independent factor in predicting the overall survival of
OC patients. CONCLUSIONS: These results suggest that NEAT1 has a potential to
function as a clinical biomarker for predicting disease invasiveness and
prognosis of patients with OC.
PMID- 27608896
TI - Exploring the regulatory role of isocitrate dehydrogenase mutant protein on
glioma stem cell proliferation.
AB - OBJECTIVE: Glioma is the most lethal form of cancer that originates mostly from
the brain and less frequently from the spine. Glioma is characterized by abnormal
regulation of glial cell differentiation. The severity of the glioma was found to
be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused
on histological discrimination and regulation of cancer stem cell between IDH1
mutant and in non-IDH1 mutant glioma tissue. PATIENTS AND METHODS: Histology,
immunohistochemistry and Western blotting techniques are used to analyze the
glioma nature and variation in glioma stem cells that differ between IDH1 mutant
and in non-IDH1 mutant glioma tissue. RESULTS: The aggressive form of non-IDH1
mutant glioma shows abnormal cellular histological variation with prominent
larger nucleus along with abnormal clustering of cells. The longer survival form
of IDH1 mutant glioma has a control over glioma stem cell proliferation.
Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to
demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem
cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal
cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it
promotes cancer stem cell proliferation. CONCLUSIONS: Our finding supports that
the IDH1 mutant glioma has a regulatory role in glioma stem cells and their
survival.
PMID- 27608897
TI - MiR-200c and miR-141 inhibit ZEB1 synergistically and suppress glioma cell growth
and migration.
AB - OBJECTIVE: This study aimed to investigate the expression of miR-200c and miR-141
in glioma tissues and cell lines and then to study their regulative effect on
ZEB1 expression and on glioma cell growth and migration. MATERIALS AND METHODS:
QRT-PCR analysis was performed to detect miR-200c and miR-141 expression in 10
paired glioma tissues and adjacent normal tissues from patients with glioblastoma
multiforme (GBM) and in glioma cell lines. U87 and U251 cells were transfected
with miR-200c mimics, miR-141 mimics or ZEB1 siRNA respectively. ZEB1 expression
was detected qRT-PCR and Western blot assay. MTT assay, flow cytometry and wound
healing assay were performed to examine the tumor suppressive effects of the miR
200c/miR-141-ZEB1 axis on glioma cells. RESULTS: Both miR-200c and miR-141 were
significantly lower in glioma tissues than in adjacent normal tissues. The glioma
cell lines, including U87, U251 and A172 also had significantly decreased miR
200c and miR-141 expression than normal tissues. ZEB1 expression had at least two
fold increase in glioma tissues than in normal tissues. Both miR-200c and miR-141
could significantly induce ZEB1 mRNA degradation and suppress ZEB1 protein
expression. ZEB1 siRNA presented similar growth and migration inhibiting and
apoptosis inducing effect to miR-200c and miR-141 mimics in U87 cells.
CONCLUSIONS: MiR-200c and miR-141 are significantly downregulated in glioma
tissues and cell lines and can significantly induce ZEB1 mRNA degradation and
suppress ZEB1 protein expression in the cells. ZEB1 is a functional downstream
target of miR-200c and miR-141 in inhibiting glioma cell growth and migration.
PMID- 27608898
TI - PHACTR4 regulates proliferation, migration and invasion of human hepatocellular
carcinoma by inhibiting IL-6/Stat3 pathway.
AB - OBJECTIVE: Phosphatase and actin regulator 4 (PHACTR4) is one member of the
largely uncharacterized PHACTR family of protein phosphatase 1 (PP1)-and actin
binding proteins. PHACTR4 is significantly deleted or mutant in many tumor
subtypes, such as breast, colorectal, lung, neural, ovarian, and renal cancers.
However, the role of PHACTR4 in human hepatocellular carcinoma (HCC) is
completely unknown. MATERIALS AND METHODS: Ten paired HCC tissues and adjacent
non-cancerous tissues were used to detect the expression PHACTR4. Real-time PCR
was used to detect the mRNA level of PHACTR4 in clinic samples. The protein level
of PHACTR4 was determined by Western blot. Retrovirus-based gene transduction was
used to generate Flag-tagged PHACTR4 HepG2 stable cell line. BrdU assay was used
to determine the cell growth of HepG2 cells. The cell cycle distribution was
detected by flow cytometry assay. In vitro scratch wounding and Matrigel invasion
assays were used to test the migration and invasion ability of HepG2 cells.
RESULTS: The expression of PHACTR4 was noticeably decreased in clinical HCC
tissues, compared to the non-tumoral tissues. Overexpression of PHACTR4 inhibited
HCC cells proliferation, colony formation, migration and invasion, and resulted
in significant cycle arrest. PHACTR4 attenuated both constitutive and IL-6
induced phosphorylation of signal transducer and activator of transcription 3
(Stat3), and inhibited Stat3 downstream genes expression. CONCLUSIONS: Overall,
our results suggest that PHACTR4 is a tumor suppressor in HCC by inhibiting IL-6/
Stat3 pathway.
PMID- 27608899
TI - Identifying the role of PTPN12 expression in predicting the efficacy of
capecitabine to neoadjuvant chemotherapy in breast cancer treatment.
AB - OBJECTIVE: The aim of this study was to investigate the expression of PTPN12 in
human breast cancer and its role in predicting the efficacy of neoadjuvant
chemotherapy (NACT) for breast cancer. PATIENTS AND METHODS: The PTPN12
expression levels were assessed by immunohistochemical staining in 114 breast
cancer patients. The correlation of PTPN12 with clinicopathological features was
also analyzed. Multivariate logistic regression was used to explore the effect of
PTPN12 expression in predicting clinical response. RESULTS: We observed a
significant association of PTPN12 expression with cTNM classification. The
overall pathological complete response (pCR) rate was 23.2 % in high PTPN12
expression group, whereas it was 5.2% in low PTPN12 expression group. The
multivariate regression analyses further indicated that clinical response
correlated with PTPN12 expression level and cycles of NACT, and CEX regimen was
associated with the overall pathological complete response. In addition, Spearman
rank correlation analyses suggested that higher PTPN12 expression indicated
better clinical response in breast cancer patients. Furthermore, PTPN12
expression statistically related with pathological response in TNBC and Luminal B
subtypes, as assessed by Pearson Chi-square test or Fisher's exact test.
CONCLUSIONS: Our study informed that cTNM classification is an independent risk
factor for PTPN12 expression and PTPN12 is an independent predictor to clinical
remission.
PMID- 27608900
TI - MiR-195 enhances cardiomyocyte apoptosis induced by hypoxia/reoxygenation injury
via downregulating c-myb.
AB - OBJECTIVE: In this study, we explored the regulative effect of miR-195 on c-myb
expression and also investigated the role of miR-195 and c-myb in cardiomyocyte
apoptosis induced by hypoxia/reoxygenation (H/R) injury. MATERIALS AND METHODS:
QRT-PCR analysis was performed to measure mature miR-195 expression. H9c2 cells
were transfected for miR-195 overexpression or knockdown or c-myb overexpression
using Lipofectamine 2000. The cells were subjected to H/R treatment and following
flow cytometric analysis of active caspase-3 or florescent study of reactive
oxygen species (ROS) generation. The binding sites between miR-195 and 3'UTR of
MYB mRNA were predicted using TargetScan 7.0. The binding sites were verified
using dual luciferase assay and Western blot analysis. RESULTS: MiR-195 is
significantly upregulated after H/R treatment in H9c2 cells. H/R injury induced
active caspase-3 expression. However, the cells with miR-195 suppression had
substantially lower ratio of cells with active caspase-3. MiR-195 can decrease c
myb protein expression. Dual luciferase assay verified two binding sites between
miR-195 and 3'UTR of MYB mRNA. C-myb overexpression can suppress mitochondrial
superoxide generation and cardiomyocyte apoptosis after H/R. CONCLUSIONS: MiR-195
is significantly increased due to H/R and can enhance cardiomyocyte apoptosis.
MYB is a target gene of miR-195 in cardiomyocytes. The miR-195-MYB axis is
involved in regulation of cardiomyocyte apoptosis induced by H/R.
PMID- 27608901
TI - A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian
subjects but not in patients with coronary heart disease.
AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with
an important role in the regulation of body weight, body mass index (BMI) and
obesity. Increased BMI that leads to obesity is a substantial risk factor for
coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265)
has been associated with CHD, obesity and BMI. The aim of the study was to
determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in
patients with CHD and healthy control subjects. PATIENTS AND METHODS: The study
included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control
subjects. The BDNF rs6265 genotype frequency was similar in male and female
subjects, and there were no differences in the frequency of the BDNF rs6265
genotypes in 206 patients with CHD and in 498 healthy subjects. When study
participants were subdivided according to the BMI categories into normal weight,
overweight and obese subjects, significantly different BDNF rs6265 genotype
frequency was found within healthy subjects, but not within patients with CHD.
Healthy subjects, but not patients with CHD, subdivided into carriers of the
Met/Met, Met/Val and Val/Val genotype, had different BMI scores. RESULTS: The
BDNF rs6265 genotype frequency was similar in male and female subjects, and there
were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients
with CHD and in 498 healthy subjects. When study participants were subdivided
according to the BMI categories into normal weight, overweight and obese
subjects, significantly different BDNF rs6265 genotype frequency was found within
healthy subjects, but not within patients with CHD. Healthy subjects, but not
patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val
genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated
with a diagnosis of CHD or with BMI categories among patients with CHD. In
contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more
frequently normal weight compared to carriers of other BDNF genotypesBDNF rs6265
polymorphism was not associated with a diagnosis of CHD or with BMI categories
among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF
Met/Met genotype, had more frequently normal weight compared to carriers of other
BDNF genotypes. CONCLUSIONS: BDNF rs6265 polymorphism is associated with BMI
categories, and the BDNF Met/Met genotype has a protective role in obesity in
healthy subjects, while this effect was not present in patients with CHD.
PMID- 27608902
TI - P wave and QT dispersion in familial mediterranean fever.
AB - OBJECTIVE: Familial mediterranean fever (FMF) is the most common auto
inflammatory disease that is characterized by recurrent, self-limited attacks of
fever and serous membrane inflammation. Patients with inflammatory rheumatic
diseases are considered to have a raised cardiovascular diseases risk. The aim of
this study was to investigate; by means of P wave dispersion (Pd) and QT
dispersion (QTd) parameters detected by simple standard electrocardiogram (ECG),
atrial and ventricular repolarization changes in pregnant women with and without
FMF. PATIENTS AND METHODS: In this case-control study including 37 pregnant women
with FMF who already put on colchicine treatment and 40 healthy, uncomplicated
pregnancy cases, were prospectively assessed using 12-lead ECG and
echocardiography. RESULTS: No differences in Pd and corrected QT values were
found between the groups. Epicardial fat thickness values were significantly
higher in the FMF group compared with the control group (p = 0.015). A positive
correlation was found between FMF duration and epicardial fat thickness (r =
0.350, p = 0.042). CONCLUSIONS: Pd, a non-invasive marker of potential atrial
arrhythmia and QT-d, a non-invasive marker of potentially lethal ventricular
tachyarrhythmia, constitute a recent contribution to the field of noninvasive
electrocardiology. Pd and QT-d values were not altered in pregnant women with FMF
who already put on colchicine treatment, with no increased risk of atrial or
ventricular arrhythmias indicated. Colchicine may have a cardio-protective effect
beyond the effect mediated through suppression of inflammation.
PMID- 27608903
TI - The impact of the extent and severity of coronary artery disease on fractional
flow reserve measurements.
AB - OBJECTIVE: Coronary angiography has a limitation to determine the severity of
intermediate stenosis (30-70%)1,2. Fractional flow reserve (FFR) is a method for
the assessment of the intermediate stenosis severity3. The effect of coronary
artery disease (CAD) severity on the FFR results is not clear. In this study, we
aimed to expose the effect of CAD severity calculated with Syntax and Gensini
scores on FFR results. PATIENTS AND METHODS: We scanned patients data (n=378) who
had undergone fractional flow reserve measurements in our center. Patients with
acute coronary syndrome in the last month, moderate or severe valvular diseases,
acute heart failure, serious bradycardia, atrial fibrillation/flutter, severe
left ventricular hypertrophy or patient with deficient data were excluded. 351
patients were included in the study. Syntax and Gensini scores were calculated
and compared with FFR results. Hemodynamically significant result for FFR, ratio
<0.80 was accepted. RESULTS: The negative correlation between high Gensini, high
Syntax scores and FFR results was statistically significant. Especially patients
with Syntax scores >22 had notable more crucial lesions in FFR measurements
(p<0.001). Cardiovascular disease risk factors such as age, gender, hypertension,
diabetes mellitus and dyslipidemia did not correlate with the FFR results.
Patients with intermediate stenosis (30-70%) and high Gensini and high Syntax
scores were found to have more hemodynamically significant on FFR measurements
(FFR <0.80). CONCLUSIONS: Intermediate lesions with high Syntax score should be
evaluated by hemodynamic procedures and treated more carefully with optimal
medical treatment or revascularization. Revascularization method of CAD with high
Syntax score should be decided with hemodynamic procedures as FFR measurements.
PMID- 27608904
TI - Influence of physical effort on aortic stiffness in young male athletes.
AB - OBJECTIVE: The progression of cardiovascular disease is blunted by regular
exercise training as a common non-pharmacological treatment. Recent findings have
confirmed that central aortic pressure is more strongly related to cardiovascular
events than brachial blood pressure. The aim of the study was to evaluate the
influence of a single bout of significant physical effort on central aortic
pressure and pulse wave velocity in young male athletes. PATIENTS AND METHODS:
The study group consisted of 16 healthy male athletes undergoing regular
endurance training. The subjects of the study (21.6 +/- 2.85 years of age)
underwent a submaximal exercise test consisting of cycling for 30 minutes. Aortic
pulse wave velocity (PWV) and derivatives (augmentation index set to 75 heart
beats, AIx75; pulse pressure amplification, PPA), ejection duration (ED),
subendocardial viability ratio (SEVR) and central blood pressure were examined
before and after the exercise test Blood pressure and pulse waveform were
evaluated in the supine position after a 15-minute rest by means of the
oscillometric method the oscillometric method. RESULTS: Comparing the rest
condition to the period immediately following the exercise test, athletes showed
lower central than peripheral systolic blood pressure both before (129 +/- 11
mmHg and 112 +/- 8 mmHg, respectively, p < 0.001) and after (130 +/- 10 mmHg to
112 +/- 8 mmHg, respectively, p < 0.001) the test. They also showed a decrease of
ED from 339.7 +/- 44.4 ms to 326.9 +/- 41.4 ms (p < 0.02) and an increase of PPA
from 136.2 +/- 5.4% to 140.3 +/- 5.0% (p < 0.02), whereas PWV, AIx75 and SEVR
changed insignificantly. CONCLUSIONS: We confirm that PPA is sensitive to an
instant change in aortic elasticity. Furthermore, the hemodynamic response to a
single physical effort composed of shorter ejection time and increased relative
elasticity of the aorta prevents impairment of oxygen supply to the heart
musculature.
PMID- 27608905
TI - AIMS baby movement scale application in high-risk infants early intervention
analysis.
AB - OBJECTIVE: We investigated the application of Alberta Infant Motor Scale (AIMS)
in screening motor development delay in the follow-up of high-risk infants who
were discharged from NICU, to explain the state of infants' motor development and
propose early individualized intervention. PATIENTS AND METHODS: The study design
was a randomized, single-blind trial by selecting patients between April 2015 and
November 2015 in our hospital, children nerve recovery branch clinics and 77
cases of high-risk infants. We randomly divided the patients into observation
group (39 cases) and control group (38 cases). To evaluate the application with
AIMS, observation group was based on evaluation results for the first time to
give rehabilitation training plan making, early intervention, control group
according to the growth and development milestone in order to guide parents to
take family training interval of 3 months. RESULTS: While comparing the two
groups of high-risk infants before the intervention, the months of age, gender,
risk factors, it was found that the AIMS scores, each position AIMS scores did
not show a significant difference in percentile (p>0.05). There was also no
significant difference between two groups in the seat and stand AIMS scores
before and after intervention (p>0.05). However, the comparison of two groups of
high-risk infants after intervention in comparison showed that the observation
group supine AIMS scores and AIMS scores were significantly higher than the
control group (p<0.05). Prone position AIMS scores observation group was also
significantly higher than that of the control group (p<0.01). The corresponding
percentile for two groups after the intervention of AIMS scores was less than 10%
of cases, which was significantly lower in the observation group (p<0.01).
CONCLUSIONS: AIMS can predict the development delay in high-risk infants, for
improving the early hypernymic diagnosis and intervention.
PMID- 27608906
TI - Helicobacter pylori infection is associated with high methane production during
lactulose breath test.
AB - OBJECTIVE: Despite a growing interest toward the interplay between H. pylori and
gastric microbiota, few data are available about this correlation. The aim of
this study was to explore the relationship between H. pylori infection and gas
production during lactulose breath test. MATERIALS AND METHODS: Data of patients
undergoing both 13C-urea breath test (UBT) and lactulose breath test (LBT) under
standard conditions in our GI unit were retrospectively analyzed. GI symptoms,
such as dyspepsia, bloating, abdominal pain/discomfort, and epigastric pain on an
eleven-point scale were also analyzed and correlate with the results of those
tests. H2 and CH4 were calculated using the trapezoidal rule; a considerable CH4
production was defined by AUCCH4 >=1200 ppm*4h. Statistical analyses were
performed with Fisher's exact test and independent samples Mann-Whitney test.
RESULTS: Data of 136 patients during a period of time of 3 months were analyzed.
36 patients (26.5%) showed a positive UBT. We do not find any difference as
regards age, sex, symptom complaints, and small intestinal bacterial overgrowth
between HP negative and positive patients. A greater methane production was
observed in infected rather than non-infected patients (47.2% vs. 26%
respectively, p=0.02). Furthermore, 25% infected and 10% non-infected produced
greater amounts of CH4 compared to H2, resulting in a AUCCH4/AUCH2 ratio >1
(p=0.046). CONCLUSIONS: This study shows for the first time, a significant
association between H. pylori infection and methane production, suggesting that
H. pylori might influence gut microbiota composition. Further studies are needed
to clarify mechanisms underlying this phenomenon.
PMID- 27608907
TI - Study to elucidate molecular mechanism behind zinc chemo-preventive role during
lung carcinogenesis.
AB - OBJECTIVE: The present planned to elucidate the mechanistic role zinc
supplementation in the modulation of p53 post-translational acetylation, the
activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters
during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. MATERIALS AND
METHODS: The mice were segregated into four groups viz., normal control, BP
treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a
single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was
supplemented to mice at dose levels of 227 mg/kg body weight in drinking water.
All the treatments were continued for 20 weeks. RESULTS: The BP caused a
significant rise in the expression of p53. On the other hand, protein expressions
of acetylated (lys382)-p53 were significantly decreased, following BP treatment.
Also, a significant decrease was observed in the enzyme activities of caspase 3
and caspase 9. Moreover, BP treatment brought about a significant increase in the
activity of COX-2. Supplementation of zinc to BP treated mice stimulated
acetylation of p53 as observed by an increase in the protein expression of
acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9
showed a significant elevation upon zinc supplementation. On the other hand, the
zinc supplementation brought about moderation in the expression of enzymatic
activity of COX-2 which was restored within the normal limits. Further, BP
treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose
uptake and its turnover which were reduced significantly following simultaneous
treatment with zinc. CONCLUSIONS: The treatment with zinc has the potential to
modulate p53 acetylation to stimulate apoptosis against experimentally induced
lung carcinogenesis.
PMID- 27608908
TI - Treatment of advanced breast cancer with a combination of highly agglutinative
staphylococcin and vinorelbine-based chemotherapy.
AB - OBJECTIVE: Breast cancer is the most frequently diagnosed cancer among women in
over 75% of countries worldwide accounting for one in four of all cancers in
women. Highly agglutinative staphylococcin (HAS), a mixture of Staphylococcus
aureus culture filtrates, has been used clinically as an immunomodifier in the
treatment of a number of tumors for many years. The aim of present study is to
evaluate the therapeutic effects and safety of treating advanced breast cancer
patients with a combined therapy of HAS and vinorelbine-based chemotherapy
compared to patients who receive standard chemotherapy alone. PATIENTS AND
METHODS: A total of 62 patients with advanced breast cancer were divided into 2
study groups. One group received intravenous injections of HAS and vinorelbine
based chemotherapy (n=31) compared to a control group assigned to receive
vinorelbine-based standard chemotherapy (n=31). RESULTS: Patients with advanced
breast cancer who received HAS combined therapy showed a significantly higher
overall response rate (Complete Response + Partial Response) of 67.7% compared
with patients who received systemic chemotherapy alone (51.6%; p < 0.05).
Overall, the occurrence of adverse effects was not significantly different
between study groups. HAS was able to remedy the immunosuppressing effects of
standard chemotherapy in these patients. CONCLUSIONS: Treatment of advanced
breast cancer with of HAS - in combination with vinorelbine-based chemotherapy -
was generally more effective and just as safe compared to treatment with
vinorelbine-based standard chemotherapy alone.
PMID- 27608909
TI - Potential protective effect of resveratrol on acoustic trauma: electron
microscopy study.
AB - OBJECTIVE: To investigate the potential preventive effect of resveratrol in rats
exposed to acoustic trauma (AT). MATERIALS AND METHODS: In this experimental
study, Wistar albino rats were divided into three groups: Group 1 (Control, n =
6), Group 2 (AT, n = 6), and Group 3 (resveratrol + AT). The rats in Group 2 were
exposed to AT. The rats in Group 3 received resveratrol (300 mg/kg/day) via
gavage for 7 days. On day 7, the rats were exposed to AT 10 min following
resveratrol treatment. Histological sections of the cochleae were examined using
light microscopy, transmission (TEM), and scanning electron microscopy (SEM).
RESULTS: The cochlear hair cells, stereocilia, and Deiters' cells of the control
group appeared normal in all microscopic evaluations. In Group 2, light
microscopy revealed predominantly inner hair cell loss, although the outer hair
cells were affected. TEM and SEM examination showed severe loss of stereocilia
and SEM revealed stereocilia arranged in an asymmetric array. The cochlear
structure in Group 3 appeared well preserved under the light microscope, and
although TEM and SEM revealed stereocilia loss, the hair cells and stereocilia
appeared near normal compared with those of Group 2. CONCLUSIONS: Resveratrol may
have a protective effect against AT damage in the cochlea, most likely through
its antioxidant activity. Our results may be useful for studies in humans exposed
to AT and noise-induced hearing loss related to chronic exposure to occupational
noise.
PMID- 27608910
TI - Anesthesia management of a patient with left ventricular assist device for
emergency open appendectomy: a case report.
AB - OBJECTIVE: The objective of this case report is to describe the management of
anesthesia of a patient with an LVAD that underwent an emergency open
appendectomy. Literature regarding emergency anesthesia management of such
patients is still limited. A search in the PubMed engine with the keywords "LVAD
appendectomy anesthesia management" revealed no results. CASE REPORT: The case
regards a 54 years old male patient that received an LVAD implant 2 months before
the current incident. Close monitoring was applied including invasive arterial
pressure measurement. Etomidate was selected for induction thanks to its'
insignificant hemodynamic effects. Careful titrated drug and liquids
administration was applied to avoid hemodynamic destabilization. Anticoagulation
treatment cannot be stopped in these patients, and there was no time for
anticoagulation treatment changes. Two units of fresh frozen plasma were issued
as preventive bleeding measures. RESULTS: No hemodynamic destabilization
(targeted MAP: 65-90 mmHg) and bleeding were registered. The patient was
extubated without any complications. CONCLUSIONS: Anesthesia management of
similar cases should be focused around bleeding and hemodynamic destabilization
and is harder in emergency surgery due to narrow time limits. Drug and liquids
titration and use of drugs with minimum hemodynamic effects are advised, as well
as close cardiovascular monitoring.
PMID- 27608911
TI - Involvement of ghrelin in nucleus tractus solitaries on gastric signal afferent
and gastric motility in cisplatin-treated rats.
AB - OBJECTIVE: Ghrelin had been known to promote gastric motility in human and
animals previously. We aim to investigate the role of ghrelin in chemotherapy
induced nausea and vomiting. MATERIALS AND METHODS: In the present study, we
observed the changes in food intake, kaolin consumption, body weight, plasma
ghrelin concentration and expression of ghrelin and its receptor GHS-R1a in the
stomach and nucleus tractus solitaries (NTS) in cisplatin-treated rats, and the
effects of ghrelin microinjected into NTS on the discharge activity of gastric
distension (GD) responsive neurons and gastric motility were also observed.
RESULTS: Cisplatin induced the decrease in food intake and the increase in kaolin
consumption of rats. In addition, mRNA expression of GHS-R1a in the stomach and
NTS increased significantly after cisplatin treatment. The discharge activity of
GD excited (GD-E) and GD inhibited (GD-I) neurons in cisplatin-treated rats was
weaker than that of saline treatment, while ghrelin administration into NTS
excited most of GD-E and GD-I neurons. Cisplatin induced the decrease in gastric
contraction while ghrelin administrated into NTS promoted the gastric motility
significantly. However, the amplitude and frequency of gastric contraction
promoted by ghrelin in NTS of cisplatin-treated rats were lower than that of
saline treated rats. The effects of ghrelin could be completely blocked by its
receptor antagonist BIM28163. CONCLUSIONS: These results indicated that ghrelin
in the NTS might participate in the regulation of GD-neurons and gastric motility
via its receptor in cisplatin-treated rats.
PMID- 27608912
TI - Porous tantalum seeded with bone marrow mesenchymal stem cells attenuates steroid
associated osteonecrosis.
AB - OBJECTIVE: Bone marrow mesenchymal stem cells (BMMSCs) have been widely applied
in osteonecrosis. However, lack of biomechanical support limited application of
BMMSCs. And porous tantalum (PTA) has been identified as a cell-friendly scaffold
for bone regeneration. Herein, we aimed to investigate the efficacy of PTA seeded
with BMMSCs in the treatment of osteonecrosis. MATERIALS AND METHODS: After the
production of PTA seeded with BMMSCs, MTT and GFP were performed to identify the
proliferation and adhesion of BMMSCs respectively, which was further examined by
scanning electron microscopy (SEM). And real-time PCR was also used to determine
mRNA level of osteogenic markers, including Alp, OCN, OPN, Col I and Runx-2 in
BMMSCs. Nineteen adult rabbits were applied for building steroid-associated
osteonecrosis (SAON) models. Bone formation rate (BFR) and mineral apposition
rate (MAR) were determined. And Goldner Trichrome Staining was used in these SAON
models, which further confirmed the efficacy of PTA seeded with BMMSCs in SAON.
RESULTS: PTA seeded with BMMSCs showed excellent biocompatibility. Additionally,
SEM assay showed that BMMSCs adhered tightly and spread fully in the pores of
PTA. Next, the expression of ALP and OPN mRNA in BMMSCs were significantly (p <
0.05) higher in the PTA-treated group compared to those in the PTA-untreated
group. Furthermore, compared to those treated by only PTA, the dynamic bone
formation in rabbits treated by PTA seeded with BMMSCs was significantly
increased (p < 0.001) at both week 3rd and week 6th. CONCLUSIONS: The product,
PTA seeded with BMMSCs, was successfully produced, and was determined as high
efficacy for treatment of steroid-associated osteonecrosis. PTA seeded with
BMMSCs may afford a promising option for treating osteonecrosis.
PMID- 27608913
TI - Dexmedetomidine regulate the malignancy of breast cancer cells by activating
alpha2-adrenoceptor/ERK signaling pathway.
AB - OBJECTIVE: Breast cancer is one of the most aggressive and pervasive cancers
identified in females. Dexmedetomidine (Dex) is an efficient anesthetic used in
surgery. Our study aimed to explore the role of Dex in the malignancy of breast
cancer cells in vitro and in vivo. Further, we investigate the molecular
mechanism involved in the function of Dex on breast cancer cells. MATERIALS AND
METHODS: The methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell
proliferation. The migration and invasion capacity of MDA-MB-231 cells was tested
by wound healing assay and transwell assay. Western blot analysis was performed
to quantify the protein expression levels of alpha2-adrenoceptor and ERK.
RESULTS: The proliferation, migration and invasion ability of MDA-MB-231 cells
was gradually increased after treatment of Dex in a dose-dependent manner in
vitro. In addition, Dex could significantly elevate the volume and weight of
xenotransplant tumor in vivo. Furthermore, Dex up-regulated the protein level of
a2-adrenoceptor and consistently enhanced the phosphorylation of ERK without
changing the total level of it. Similarity, over-expression of a2-adrenoceptor
via its agonist Clonidine could mimic the function of Dex on breast cancer.
CONCLUSIONS: These data suggest that Dex could promote the proliferation,
migration and invasion of breast cancer cells through the activation of alpha2B
adrenoceptor /ERK signaling.
PMID- 27608914
TI - Leptin improves osteoblast differentiation of human bone marrow stroma stem
cells.
AB - OBJECTIVE: To study the effects of leptin (LEP) on the osteogenic differentiation
of human bone marrow stromal cells (hBMSCs) and to explore the mechanism
controlling the process. MATERIALS AND METHODS: Respectively cultivated the third
generation hBMSCs with 100 ng/ml bone morphogenetic protein (BMP) culture media
containing 320, 160, 80 and 40 ng/mL LEP, and regular medium. We administered
alkaline phosphatase (ALP) dye (on the 7th day) and mineralized nodules alizarin
red (on the 21st day) and tested the ALP activity as well as osteocalcin (OCN)
level on 7th, 14th, 21st day in each group to establish the best inducing
concentration of LEP. 7 days later, we tested bone differentiation related genes
expression in the control, 160 ng/mL LEP and 100 ng/mL BMP groups using RT-PCR.
RESULTS: The activity of ALP and OCN in the 160 ng/mL LEP group after 7, 14 and
21 days was lower than that of the BMP group but higher than that of other
groups. However, LEP significantly promoted the expression of bone
differentiation related genes, namely, Cbfal, ALP, COL-I and OCN. CONCLUSIONS:
LEP promoted the bone differentiation in hBMSCs by promoting the expression of
genes related to bone differentiation.
PMID- 27608916
TI - Structural relaxation and diffusion in a model colloid-polymer mixture: dynamical
density functional theory and simulation.
AB - Within the Asakura-Oosawa model, we study structural relaxation in mixtures of
colloids and polymers subject to Brownian motion in the overdamped limit. We
obtain the time evolution of the self and distinct parts of the van Hove
distribution function G(r,t) by means of dynamical density functional theory
(DDFT) using an accurate free-energy functional based on Rosenfeld's fundamental
measure theory. In order to remove unphysical interactions within the self part,
we extend the recently proposed quenched functional framework (Stopper et al 2015
J. Chem. Phys. 143 181105) toward mixtures. In addition, we obtain results for
the long-time self diffusion coefficients of colloids and polymers from dynamic
Monte Carlo simulations, which we incorporate into the DDFT. From the resulting
DDFT equations we calculate G(r, t), which we find to agree very well with our
simulations. In particular, we examine the influence of polymers which are slow
relative to the colloids-a scenario for which both DDFT and simulation show a
significant peak forming at r = 0 in the colloid-colloid distribution function,
akin to experimental findings involving gelation of colloidal suspensions.
Moreover, we observe that, in the presence of slow polymers, the long-time self
diffusivity of the colloids displays a maximum at an intermediate colloid packing
fraction. This behavior is captured by a simple semi-empirical formula, which
provides an excellent description of the data.
PMID- 27608917
TI - Information and organization in public health institutes: an ontology-based
modeling of the entities in the reception-analysis-report phases.
AB - BACKGROUND: Ontologies are widely used both in the life sciences and in the
management of public and private companies. Typically, the different offices in
an organization develop their own models and related ontologies to capture
specific tasks and goals. Although there might be an overall coordination, the
use of distinct ontologies can jeopardize the integration of data across the
organization since data sharing and reusability are sensitive to modeling
choices. RESULTS: The paper provides a study of the entities that are typically
found at the reception, analysis and report phases in public institutes in the
life science domain. Ontological considerations and techniques are introduced and
their implementation exemplified by studying the Istituto Zooprofilattico
Sperimentale delle Venezie (IZSVe), a public veterinarian institute with
different geographical locations and several laboratories. Different modeling
issues are discussed like the identification and characterization of the main
entities in these phases; the classification of the (types of) data; the
clarification of the contexts and the roles of the involved entities. The study
is based on a foundational ontology and shows how it can be extended to a
comprehensive and coherent framework comprising the different institute's roles,
processes and data. In particular, it shows how to use notions lying at the
borderline between ontology and applications, like that of knowledge object. The
paper aims to help the modeler to understand the core viewpoint of the
organization and to improve data transparency. CONCLUSIONS: The study shows that
the entities at play can be analyzed within a single ontological perspective
allowing us to isolate a single ontological framework for the whole organization.
This facilitates the development of coherent representations of the entities and
related data, and fosters the use of integrated software for data management and
reasoning across the company.
PMID- 27608919
TI - Degradation Kinetics Study of Alogliptin Benzoate in Alkaline Medium by Validated
Stability-Indicating HPTLC Method.
AB - A rapid, sensitive, and stability-indicating high-performance thin-layer
chromatographic method was developed and validated to study degradation kinetics
of Alogliptin benzoate (ALG) in an alkaline medium. ALG was degraded under
acidic, alkaline, oxidative, and thermal stress conditions. The degraded samples
were chromatographed on silica gel 60F254-TLC plates, developed using a
quaternary-solvent system (chloroform-methanol-ethyl acetate-triethyl amine,
9+1+1+0.5, v/v/v/v), and scanned at 278 nm. The developed method was validated
per International Conference on Harmonization guidelines using validation
parameters such as specificity, linearity and range, precision, accuracy, LOD,
and LOQ. The linearity range for ALG was 100-500 ng/band (correlation coefficient
= 0.9997) with an average recovery of 99.47%. The LOD and LOQ for ALG were 9.8
and 32.7 ng/band, respectively. The developed method was successfully applied for
the quantitative estimation of ALG in its synthetic mixture with common
excipients. Degradation kinetics of ALG in an alkaline medium was studied by
degrading it under three different temperatures and three different
concentrations of alkali. Degradation of ALG in the alkaline medium was found to
follow first-order kinetics. Contour plots have been generated to predict
degradation rate constant, half-life, and shelf life of ALG in various
combinations of temperature and concentration of alkali using Design Expert
software.
PMID- 27608918
TI - Genome and metagenome analyses reveal adaptive evolution of the host and
interaction with the gut microbiota in the goose.
AB - The goose is an economically important waterfowl that exhibits unique
characteristics and abilities, such as liver fat deposition and fibre digestion.
Here, we report de novo whole-genome assemblies for the goose and swan goose and
describe the evolutionary relationships among 7 bird species, including domestic
and wild geese, which diverged approximately 3.4~6.3 million years ago (Mya). In
contrast to chickens as a proximal species, the expanded and rapidly evolving
genes found in the goose genome are mainly involved in metabolism, including
energy, amino acid and carbohydrate metabolism. Further integrated analysis of
the host genome and gut metagenome indicated that the most widely shared
functional enrichment of genes occurs for functions such as
glycolysis/gluconeogenesis, starch and sucrose metabolism, propanoate metabolism
and the citrate cycle. We speculate that the unique physiological abilities of
geese benefit from the adaptive evolution of the host genome and symbiotic
interactions with gut microbes.
PMID- 27608920
TI - Biosynthesis of Cr(III) nanoparticles from electroplating wastewater using
chromium-resistant Bacillus subtilis and its cytotoxicity and antibacterial
activity.
AB - The aim of this study was to synthesize and characterize Cr(III) nanoparticles
using wastewater from electroplating industries and chromium-resistant Bacillus
subtilis. Formation of Cr(III) nanoparticles was confirmed by UV-visible (UV-Vis)
spectroscopy at 300 nm. The size of the nanoparticles varied from 4 to 50 nm and
energy dispersive spectroscopy profile shows strong Cr peak approximately at 4.45
and 5.2 keV. The nanoparticles inhibited the growth of pathogenic bacteria
Staphylococcus aureus and Escherichia coli. The cytotoxic effect of the
synthesized Cr(III) nanoparticle was studied using HEK 293 cells, and the cell
viability was found to decrease with increasing concentration of Cr(III)
nanoparticles.
PMID- 27608921
TI - Lunch at school and children's cognitive functioning in the early afternoon:
results from the Cognition Intervention Study Dortmund Continued (CoCo).
AB - Studies about effects of school lunch on children's cognition are rare; two
previous studies (CogniDo, CogniDo PLUS) generally found no negative effects of
lunch on children's cognitive performance at the end of lunch break (i.e. 45 min
after finishing lunch), but suggested potential beneficial effects for single
parameters. Therefore, the present study investigated the hypothesis of potential
positive effects of school lunch on cognitive performance at early afternoon (90
min after finishing lunch). A randomised, cross-over intervention trial was
conducted at a comprehensive school with fifth and sixth grade students.
Participants were randomised into two groups: On day 1, group 1 did not eat
lunch, whereas group 2 received lunch ad libitum. On day 2 (1 week later), group
2 did not eat lunch and group 1 received lunch ad libitum. The cognitive
parameters task switching, working memory updating and alertness were tested
using a computerised test battery 90 min after finishing the meal. Of the 204
recruited children, fifty were excluded because of deviations from the study
protocol or absence on one of the 2 test days, which resulted in 154
participants. Data showed no significant effects of lunch on task switching,
working memory updating and alertness (P values between 0.07 and 0.79). The
present study suggests that school lunch does not seem to have beneficial effects
on children's cognitive functions regarding the conducted tests at early
afternoon. Together with our previous studies, we conclude that school lunch in
general has no negative effects on cognitive performance in children. However,
beneficial effects seem to be restricted to a relatively short time period after
eating lunch.
PMID- 27608922
TI - Genomic identification, characterization and differential expression analysis of
SBP-box gene family in Brassica napus.
AB - BACKGROUND: SBP-box genes belong to one of the largest families of transcription
factors. Though members of this family have been characterized to be important
regulators of diverse biological processes, information of SBP-box genes in the
third most important oilseed crop Brassica napus is largely undefined. RESULTS:
In the present study, by whole genome bioinformatics analysis and transcriptional
profiling, 58 putative members of SBP-box gene family in oilseed rape (Brassica
napus L.) were identified and their expression pattern in different tissues as
well as possible interaction with miRNAs were analyzed. In addition, B. napus
lines with contrasting branch angle were used for investigating the involvement
of SBP-box genes in plant architecture regulation. Detailed gene information,
including genomic organization, structural feature, conserved domain and
phylogenetic relationship of the genes were systematically characterized. By
phylogenetic analysis, BnaSBP proteins were classified into eight distinct groups
representing the clear orthologous relationships to their family members in
Arabidopsis and rice. Expression analysis in twelve tissues including vegetative
and reproductive organs showed different expression patterns among the SBP-box
genes and a number of the genes exhibit tissue specific expression, indicating
their diverse functions involved in the developmental process. Forty-four SBP-box
genes were ascertained to contain the putative miR156 binding site, with 30 and
14 of the genes targeted by miR156 at the coding and 3'UTR region, respectively.
Relative expression level of miR156 is varied across tissues. Different
expression pattern of some BnaSBP genes and the negative correlation of
transcription levels between miR156 and its target BnaSBP gene were observed in
lines with different branch angle. CONCLUSIONS: Taken together, this study
represents the first systematic analysis of the SBP-box gene family in Brassica
napus. The data presented here provides base foundation for understanding the
crucial roles of BnaSBP genes in plant development and other biological
processes.
PMID- 27608924
TI - Response to: Comment on "Evaluation of Antiviral Therapy Performed after Curative
Therapy in Patients with HBV-Related Hepatocellular Carcinoma: An Updated Meta
Analysis".
PMID- 27608923
TI - On the assessment of coordination between upper extremities: towards a common
language between rehabilitation engineers, clinicians and neuroscientists.
AB - Well-developed coordination of the upper extremities is critical for function in
everyday life. Interlimb coordination is an intuitive, yet subjective concept
that refers to spatio-temporal relationships between kinematic, kinetic and
physiological variables of two or more limbs executing a motor task with a common
goal. While both the clinical and neuroscience communities agree on the relevance
of assessing and quantifying interlimb coordination, rehabilitation engineers
struggle to translate the knowledge and needs of clinicians and neuroscientists
into technological devices for the impaired. The use of ambiguous definitions in
the scientific literature, and lack of common agreement on what should be
measured, present large barriers to advancements in this area. Here, we present
the different definitions and approaches to assess and quantify interlimb
coordination in the clinic, in motor control studies, and by state-of-the-art
robotic devices. We then propose a taxonomy of interlimb activities and give
recommendations for future neuroscience-based robotic- and sensor-based
assessments of upper limb function that are applicable to the everyday clinical
practice. We believe this is the first step towards our long-term goal of
unifying different fields and help the generation of more consistent and
effective tools for neurorehabilitation.
PMID- 27608925
TI - Direct oral anticoagulants (DOACs) and pregnancy: A plea for better information.
PMID- 27608927
TI - Corrigendum: Virtual unrolling and deciphering of Herculaneum papyri by X-ray
phase-contrast tomography.
PMID- 27608926
TI - The effectiveness of the peer delivered Thinking Healthy Plus (THPP+) Programme
for maternal depression and child socio-emotional development in Pakistan: study
protocol for a three-year cluster randomized controlled trial.
AB - BACKGROUND: The negative effects of perinatal depression on the mother and child
start early and persist throughout the lifecourse (Lancet 369(9556):145-57, 2007;
Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99-101, 1997; J Pak Med
Assoc 60(4):329; J Psychosoma Res 49(3):207-16, 2000; Clin Child Fam Psychol Rev
14(1):1-27, 2011). Given that 10-35 % of children worldwide are exposed to
perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37-54,
1996), mitigating this intergenerational risk is a global public health priority
(Perspect Public Health 129(5):221-7, 2009; Trop Med Int Health 13(4):579-83,
2008; Br Med Bull 101(1):57-79, 2012). However, it is not clear whether
intervention with depressed women can have long-term benefits for the mother
and/or her child. We describe a study of the effectiveness of a peer-delivered
depression intervention delivered through 36 postnatal months, the Thinking
Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural
Pakistan. METHODS/DESIGN: The THPP+ study aims are: (1) to evaluate the effects
of an extended 36-month perinatal depression intervention on maternal and index
child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to
determine whether outcomes among index children of perinatally depressed women in
the intervention arm converge with those of index children born to perinatally
nondepressed women. The trial is designed to recruit 560 pregnant women who
screened positive for perinatal depression (PHQ-9 score >=10) from 40 village
clusters, of which 20 receive the THPP+ intervention. An additional reference
group consists of 560 perinatally nondepressed women from the same 40 clusters as
the THPP+ trial. The women in the nondepressed group are not targeted to receive
the THPP+ intervention; but, by recruiting pregnant women from both intervention
and control clusters, we are able to evaluate any carryover effects of the THPP+
intervention on the women and their children. Perinatally depressed women in the
THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes
are 3-year maternal depression and 3-year child development indicators. Analyses
are intention-to-treat and account for the clustered design. DISCUSSION: This
trial, together with the reference group, has the potential to further our
understanding of the early developmental lifecourse of children of both
perinatally depressed and perinatally nondepressed women in rural Pakistan and to
determine whether intervening with women's depression in the perinatal period can
mitigate the negative effects of maternal depression on 36-month child
development. TRIAL REGISTRATION: THPP-P ClinicalTrials.gov Identifier:
NCT02111915 (registered on 9 April 2014). THPP+ ClinicalTrials.gov Identifier:
NCT02658994 (registered on 21 January 2016). SPONSOR: Human Development Research
Foundation (HDRF).
PMID- 27608929
TI - Tracing the Attention of Moving Citizens.
AB - With the widespread use of mobile computing devices in contemporary society, our
trajectories in the physical space and virtual world are increasingly closely
connected. Using the anonymous smartphone data of 1 * 10(5) users in a major city
of China, we study the interplay between online and offline human behaviors by
constructing the mobility network (offline) and the attention network (online).
Using the network renormalization technique, we find that they belong to two
different classes: the mobility network is small-world, whereas the attention
network is fractal. We then divide the city into different areas based on the
features of the mobility network discovered under renormalization. Interestingly,
this spatial division manifests the location-based online behaviors, for example
shopping, dating, and taxi-requesting. Finally, we offer a geometric network
model to help us understand the relationship between small-world and fractal
networks.
PMID- 27608928
TI - Multifunctional Polymer-Based Graphene Foams with Buckled Structure and Negative
Poisson's Ratio.
AB - In this study, we report the polymer-based graphene foams through combination of
bottom-up assembly and simple triaxially buckled structure design. The resulting
polymer-based graphene foams not only effectively transfer the functional
properties of graphene, but also exhibit novel negative Poisson's ratio (NPR)
behaviors due to the presence of buckled structure. Our results show that after
the introduction of buckled structure, improvement in stretchability, toughness,
flexibility, energy absorbing ability, hydrophobicity, conductivity,
piezoresistive sensitivity and crack resistance could be achieved simultaneously.
The combination of mechanical properties, multifunctional performance and unusual
deformation behavior would lead to the use of our polymer-based graphene foams
for a variety of novel applications in future such as stretchable capacitors or
conductors, sensors and oil/water separators and so on.
PMID- 27608930
TI - Cytotoxicity of Experimental Resin Composites on Mesenchymal Stem Cells Isolated
from Two Oral Sources.
AB - Resin composite materials that are used to restore tooth cervical lesions
associated with gingival recessions can hamper healing after root coverage
surgeries. This study evaluates the in vitro cytotoxic effect of five resin
composites (two commercial and three experimental) on oral mesenchymal stem cells
(MSCs) and the persistence of stemness properties in high passage MSCs. Sorption
and solubility tests were made for all materials. MSCs were isolated from re
entry palatal and periodontal granulation tissues and were characterized and
cultured on composite discs. Cytotoxicity of the materials was evaluated by the
Alamar Blue viability test, by Paul Karl Horan (PKH) labeling, and by
immunocytochemical staining for actin. Water and saliva sorption and solubility
data revealed that two of the experimental materials behaved comparable with the
marketed resin composites. The Alamar Blue viability test shows that both cell
lines grew well on composite discs that seemed to induce no apparent toxic
effects. No signs of disruption of cytoskeleton organization was seen.
Experimental resin composites can be recommended for further investigation for
obtaining approval for use. The standard minimal criteria were fulfilled for high
passage MSCs. Palatal tissue regains its regenerative properties in terms of MSC
presence in the re-entry area after 6 months of healing.
PMID- 27608932
TI - Pandemic H1N1 Vaccination and Incidence of Acute Disseminated Encephalomyelitis
in Manitoba.
AB - BACKGROUND: An increased incidence of hospital admissions coded as acute
disseminated encephalomyelitis (ADEM) was noted in Winnipeg, Manitoba, Canada,
during the second wave of the influenza pandemic from October 2009 to March 2010.
However, it was not clear whether this was due to heightened awareness of
potential neurological complications of influenza or influenza vaccination or an
actual increase in the number of cases. METHODS: We extracted data from the
charts of 139 patients hospitalized with an International Classification of
Diseases-10 discharge code indicating ADEM (G04.0) or unspecified noninfectious
encephalitis or myelitis (G04.8, G04.9) between January 2006 and December 2012.
Clinical and laboratory data were reviewed by a neurologist, and diagnoses were
determined using the Brighton criteria. RESULTS: Over the entire study period,
there were 22 cases of ADEM. During the peak pandemic period (April-December
2009), seven patients were hospitalized with ADEM, corresponding to a rate of
7.8/million/year; 4.7 (95% confidence interval: 1.9-11.4) times higher than the
rate before or after the pandemic period. Only one patient with ADEM had received
the monovalent A(H1N1)pdm09 vaccine within 12 weeks of hospitalization.
CONCLUSIONS: We have found an increased incidence of ADEM during the pandemic
period that may be related, at least in part, to the increased incidence of
influenza during that period. However, there was no temporal relationship with
the administration of A(H1N1)pdm09 or seasonal influenza vaccines. Our study
provides reassurance that use of these vaccines was not associated with increased
risk of ADEM.
PMID- 27608931
TI - Selective de-repression of germ cell-specific genes in mouse embryonic
fibroblasts in a permissive epigenetic environment.
AB - Epigenetic modifications play crucial roles on establishment of tissue-specific
transcription profiles and cellular characteristics. Direct conversions of
fibroblasts into differentiated tissue cells by over-expression of critical
transcription factors have been reported, but the epigenetic mechanisms
underlying these conversions are still not fully understood. In addition,
conversion of somatic cells into germ cells has not yet been achieved. To
understand epigenetic mechanisms that underlie germ cell characteristics, we
attempted to use defined epigenetic factors to directly convert mouse embryonic
fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell
specific genes by inhibiting repressive epigenetic modifications via RNAi or
small-molecule compounds. Under these conditions, some tissue-specific genes and
stimulus-inducible genes were also induced. Meanwhile, the treatments did not
result in genome-wide transcriptional activation. These results suggested that a
permissive epigenetic environment resulted in selective de-repression of stimulus
and differentiation-inducible genes including germ cell-specific genes in MEFs.
PMID- 27608933
TI - Producing a socially accountable medical school: AMEE Guide No. 109.
AB - Health systems worldwide are confronted with challenges due to increased demand
from their citizens, an aging population, a variety of health risks and limited
resources. Key health stakeholders, including academic institutions and medical
schools, are urged to develop a common vision for a more efficient and equitable
health sector. It is in this environment that Boelen and Heck defined the concept
of the "Social Accountability of Medical Schools" - a concept that encourages
schools to produce not just highly competent professionals, but professionals who
are equipped to respond to the changing challenges of healthcare through re
orientation of their education, research and service commitments, and be capable
of demonstrating a positive effect upon the communities they serve. Social
Accountability calls on the academic institution to demonstrate an impact on the
communities served and thus make a contribution for a just and efficient health
service, through mutually beneficial partnerships with other healthcare
stakeholders. The purpose of this Guide is to explore the concept of Social
Accountability, to explain it in more detail through examples and to identify
ways to overcome obstacles to its development. Although in the Guide reference is
frequently made to medical schools, the concept is equally applicable to all
forms of education allied to healthcare.
PMID- 27608934
TI - How to open a Ryanodine Receptor.
AB - Ryanodine Receptors are large ion channels responsible for the release of Ca from
the Endoplasmic and Sarcoplasmic Reticulum, a prerequisite for muscle
contraction. Recent cryo-electron microscopy data have allowed a direct
visualization of allosteric motions within these membrane protein giants.
PMID- 27608935
TI - Hypoxia potentially promotes Tibetan longevity.
PMID- 27608936
TI - Feed-based vaccination regime against streptococcosis in red tilapia, Oreochromis
niloticus x Oreochromis mossambicus.
AB - BACKGROUND: Streptococcosis is an important disease of tilapia throughout the
world. In Malaysia, streptococcosis outbreak was commonly reported during the 3
month period of high water temperature between April and July. This study
describes the duration of protection following single and double booster dose
regimes against streptococcosis in tilapia using a feed-based vaccine containing
formalin-killed Streptococcus agalactiae. A total of 510 tilapias of 120 +/- 10 g
were selected and divided into 3 groups. Fish of Group 1 were vaccinated at weeks
0 and 2 (single booster group) while fish of Group 2 were vaccinated at weeks 0,
2 and 6 (double booster group) with a feed-based vaccine against streptococcosis.
Fish of Group 3 was not vaccinated. Serum samples were collected weekly to
determine the antibody level while samples of eye, brain and kidney were
collected for bacterial isolation. At week 10, all fish were challenged with live
S. agalactiae and the survival rate was determined. RESULTS: Both vaccinated
groups showed significant (p < 0.05) increase in the antibody levels following
the first booster dose, which lasted until week 6. Group 2 showed consistent high
level of antibody following the second booster dose at week 6 and remained high
until week 12. Challenge trial at week 10 resulted in 45 %, 70 % and 0 % rate of
survival for Groups 1, 2 and 3, respectively. CONCLUSION: Double booster regime
is most suitable to be applied for feed-based vaccination against streptococcosis
prior to the start of the hot season.
PMID- 27608938
TI - Meta-analysis of Cumulative Radiation Duration and Dose During EVAR Using Mobile,
Fixed, or Fixed/3D Fusion C-Arms.
AB - PURPOSE: To investigate the total fluoroscopy time and radiation exposure dose
during endovascular aortic repairs using mobile, fixed, or fixed C-arms with 3
dimensional image fusion (3D-IF). METHODS: A systematic search was performed to
identify original articles reporting fluoroscopy time (FT) and the kerma area
product (KAP) during endovascular aortic repairs. Data were grouped by noncomplex
or complex (fenestrated, branched, or chimney) repairs and stratified by type of
C-arm. The search identified 27 articles containing 51 study groups (35
noncomplex and 16 complex) that included 3444 patients. Random-effects meta
analysis and meta-regression models were used to calculate the pooled mean
estimates of KAP and FT, as well as any effect of equipment or type of
intervention. Results are presented with the 95% confidence interval and the
statistical heterogeneity (I2). RESULTS: Within the noncomplex procedure studies,
a significant (p<0.001) increase was found in the pooled mean KAP estimate in the
fixed C-arm group (181 Gy.cm2, 95% CI 129 to 233; I2=99.7) compared with the
mobile C-arm (78 Gy.cm2, 95% CI 59.6 to 97.3; I2=99.6). For complex cases, use of
3D-IF showed a significantly (p<0.001) lower mean KAP (139 Gy.cm2, 95% CI 85 to
191; I2=94%) compared to using fixed C-arms without 3D-IF (487 Gy.cm2, 95% CI 331
to 643; I2=94%). CONCLUSION: For equivalent fluoroscopy times, the use of a fixed
C-arm in noncomplex procedures leads to higher patient radiation doses compared
to a mobile C-arm. Complex procedures, which are predominantly performed using
fixed C-arms, are associated with the highest radiation dose per intervention.
Using fixed C-arms combined with 3D-IF techniques during complex cases might seem
an adequate method to compensate for the higher radiation doses measured when a
fixed C-arm is used.
PMID- 27608939
TI - Association of Ankle-Brachial Index and Aortic Arch Calcification with Overall
and Cardiovascular Mortality in Hemodialysis.
AB - Peripheral artery occlusive disease and vascular calcification are highly
prevalent in hemodialysis (HD) patients, however the association of the
combination of ankle-brachial index (ABI) and aortic arch calcification (AoAC)
with clinical outcomes in patients undergoing HD is unknown. In this study, we
investigated whether the combination of ABI and AoAC is independently associated
with overall and cardiovascular mortality in HD patients. The median follow-up
period was 5.7 years. Calcification of the aortic arch was assessed by chest X
ray. Forty-seven patients died including 24 due to cardiovascular causes during
the follow-up period. The study patients were stratified into four groups
according to an ABI < 0.95 or >=0.95 and an AoAC score of >4 or <=4 according to
receiver operating characteristic curve. Those with an ABI < 0.95 and AoAC > 4
(vs. ABI >= 0.95 and AoAC score <= 4) were associated with overall (hazard ratio
[HR], 4.913; 95% confidence interval [CI], 1.932 to 12.497; p = 0.001) and
cardiovascular (HR, 3.531; 95% CI, 1.070 to 11.652; p = 0.038) mortality in
multivariable analysis. The combination of a low ABI and increased AoAC was
associated with increased overall and cardiovascular mortality in patients
undergoing HD.
PMID- 27608937
TI - Microbiome Changes during Tuberculosis and Antituberculous Therapy.
AB - The critical role of commensal microbiota in the human body has been increasingly
recognized, and our understanding of its implications in human health and disease
has expanded rapidly. The lower respiratory tract contains diverse communities of
microbes known as lung microbiota, which are present in healthy individuals and
in individuals with respiratory diseases. The dysbiosis of the airway microbiota
in pulmonary tuberculosis (TB) may play a role in the pathophysiological
processes associated with TB disease. Recent studies of the lung microbiome have
pointed out changes in lung microbial communities associated with TB and other
lung diseases and have also begun to elucidate the profound effects that
antituberculous drug therapy can have on the human lung microbiome composition.
In this review, the potential role of the human microbiome in TB pathogenesis and
the changes in the human microbiome with Mycobacterium tuberculosis infection and
TB therapy are presented and discussed.
PMID- 27608942
TI - Editorial Comment.
PMID- 27608940
TI - CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and
meta-analysis.
AB - CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important
role in tumor progression and a number of studies have suggested that it is an
indicator of tumor prognosis. This current meta-analysis systematically
reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We
searched PubMed and Embase databases to screen the literature. Fixed-effect and
random-effect meta-analytical techniques were used to correlate CD147 expression
with outcome measures. A total of 53 studies that included 68 datasets were
eligible for inclusion in the final analysis. We found a significant association
between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall
survival, disease-specific survival, progression-free survival, metastasis-free
survival or recurrence-free survival, irrespective of the model analysis. In
addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy
drugs resistance. CD147/EMMPRIN is a central player in tumor progression and
predicts a poor prognosis, including in patients who have received chemo
radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a
potential therapeutic target for cancers.
PMID- 27608941
TI - The introduction of emergency cricothyroidotomy simulation training in Zimbabwe
contributed to the saving of two lives.
AB - BACKGROUND: In developing countries with limited access to ENT services,
performing emergency cricothyroidotomy in patients with upper airway obstruction
may be a life-saving last resort. An established Danish-Zimbabwean collaboration
of otorhinolaryngologists enrolled Zimbabwean doctors into a video-guided
simulation training programme on emergency cricothyroidotomy. This paper presents
the positive effect of this training, illustrated by two case reports. CASE
REPORTS: A 56-year-old female presented with upper airway obstruction due to a
rapidly progressing infectious swelling of the head and neck progressing to
cardiac arrest. Cardiopulmonary resuscitation was initiated and a secure surgical
airway was established via an emergency cricothyroidotomy, saving the patient. A
70-year-old male presented with upper airway obstruction secondary to intubation
for an elective procedure. When extubated, the patient exhibited severe stridor
followed by respiratory arrest. Re-intubation attempts were unsuccessful and
emergency cricothyroidotomy was performed to secure the airway, preserving the
life of the patient. CONCLUSION: Emergency cricothyroidotomy training should be
considered for all surgeons, anaesthetists and, eventually, emergency and
recovery room personnel in developing countries. A video-guided simulation
training programme on emergency cricothyroidotomy in Zimbabwe proved its value in
this regard.
PMID- 27608944
TI - Views from the frontline: reactions to the strike suspension.
PMID- 27608943
TI - Parathyroid hormone 1-34 reduces dexamethasone-induced terminal differentiation
in human articular chondrocytes.
AB - Intra-articular injection of dexamethasone (Dex) is occasionally used to relieve
pain and inflammation in osteoarthritis (OA) patients. Dex induces terminal
differentiation of chondrogenic mesenchymal stem cells in vitro and causes
impaired longitudinal skeletal growth in vivo. Parathyroid hormone 1-34 (PTH 1
34) has been shown to reverse terminal differentiation of osteoarthritic
articular chondrocytes. We hypothesized that Dex induces terminal differentiation
of articular chondrocytes and that this effect can be mitigated by PTH 1-34
treatment. We tested the effect of Dex on terminal differentiation in human
articular chondrocytes and further tested if PTH 1-34 reverses the effects. We
found that Dex treatment downregulated chondrogenic-induced expressions of SOX-9,
collagen type IIa1 (Col2a1), and aggrecan and reduced synthesis of cartilaginous
matrix (Col2a1 and sulfated glycosaminoglycan) synthesis. Dex treatment
upregulated chondrocyte hypertrophic markers of collagen type X and alkaline
phosphatase at mRNA and protein levels, and it increased the cell size of
articular chondrocytes and induced cell death. These results indicated that Dex
induces terminal differentiation of articular chondrocytes. To test whether PTH 1
34 treatment reverses Dex-induced terminal differentiation of articular
chondrocytes, PTH 1-34 was co-administered with Dex. Results showed that PTH 1-34
treatment reversed both changes of chondrogenic and hypertrophic markers in
chondrocytes induced by Dex. PTH 1-34 also decreased Dex-induced cell death. PTH
1-34 treatment reduces Dex-induced terminal differentiation and apoptosis of
articular chondrocytes, and PTH 1-34 treatment may protect articular cartilage
from further damage when received Dex administration.
PMID- 27608945
TI - [Quality scale for preschool spirometry interpretation].
AB - INTRODUCTION: Since 2007, there are international guidelines for implementation
and interpretation of spirometry in preschool children. A percentage of these
patients cannot obtain maneuvers that meet all eligibility criteria. The
objective of this study was to develop a quality scale for interpreting these
partially acceptable spirometry. MATERIAL AND METHOD: Delphi methodology was
used, which allows to reach consensus among experts analyzing a defined problem.
We invited to participate pediatric pneumologists dedicated to lung function and
who participated actively in scientific specialty societies in Chile. Successive
rounds were conducted with questionnaires about criteria used to assess
spirometry in preschool children. These criteria define the acceptability of
spirometric maneuvers according to international guidelines. Proposed quality
grades were "very good", "good", "fair" and "bad". RESULTS: Thirteen of the 15
invited experts accepted our invitation. In the first round 9 disagreed with the
degree of "regular" quality. In the second round this was removed and 11 experts
answered, 9 of them agreed with the use of this new version. The most contentious
criterion was the end of expiration. CONCLUSION: Most experts agreed with the
final scale, using "very good", "good" and "bad" judgments. This would help to
improve the performance of spirometry in children between 2 and 5 years.
PMID- 27608946
TI - Novel chinmedomics strategy for discovering effective constituents from ShenQiWan
acting on ShenYangXu syndrome.
AB - Elucidation of the efficacy of traditional Chinese medicine (TCM) is of
importance for scientists of modern medicine to understand the value of TCM
clinical experience, and it is necessary to have a biological language to
scientifically describe the efficacy of TCM. With this background?Chinmedomics
has been proposed by our team, which includes integrating serum pharmacochemistry
and metabolomics technology, defining theory and research methods for expressing
the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and
elucidating the efficacy of TCM formulae, discovering effective constituents, and
finally elucidating the scientific value of TCM. In the present study, the
innovative chinmedomics strategy was conducted to evaluate the therapeutic
effects of ShenQiWan (SQW) acting on ShenYangXu (kidney-yang deficiency syndrome,
KYDS). We analyzed the urine metabolic trajectory between the model and control
groups, and identified the biomarkers by the multivariate analysis. We found that
SQW caused significant restoration of abnormal metabolism of KYDs. Using the
method of metabolomics, 17 potential urine biomarkers were analyzed through 4
repeated tests in our serial studies on SQW and KYDS. Under the premise of
therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo
by the use of serum pharmacochemistry. Correlation analysis between marker
metabolites and in vivo constituents of SQW showed that 28 compositions had a
close relationship with urine biomarkers of therapeutic effects, whichmight play
a key role in the therapeutic effect of SQW. These compounds were imported into
an online database to predict their targets. Twenty-three important potential
targets were identified, which were related to the metabolism of steroid hormone,
tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a
useful strategy for discovery of potentially effective constituents from complex
TCM formulae.
PMID- 27608947
TI - NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell
death in non-small cell lung cancer cells.
AB - Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting
step in converting nicotinamide to NAD(+), essential for a number of enzymes and
regulatory proteins involved in a variety of cellular processes, including
deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53
and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and beta
lapachone (beta-lap) induced a rapid depletion of NAD(+) pool but adaptively a
significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose
significantly enhanced NQO1-targeting agent-induced apoptotic cell death.
Compared with TSA or beta-lap treatment alone, co-treatment with FK866 induced a
more dramatic depletion of NAD(+), repression of SIRT1 activity, and thereby the
increased accumulation of acetylated FOXO1 and the activation of apoptotic
pathway. In conclusion, the results from the present study support that NAMPT
inhibition can synergize with NQO1 activation to induce apoptotic cell death,
thereby providing a new rationale for the development of combinative therapeutic
drugs in combating non-small lung cancer.
PMID- 27608948
TI - Traditional herbal formula Sini Powder extract produces antidepressant-like
effects through stress-related mechanisms in rats.
AB - Sini Powder (SP), a traditional Chinese herbal formula, has long been used to
treat depression in patients, although the underlying mechanisms remain to be
elucidated. In the present study, we found that rats treated with SP extract for
7 days showed a significant increase in swimming time and reduction in immobility
time in forced swimming test in a dose-dependent manner, without changes in
locomotion. These effects could be attributed to SP's modulation of the
hypothalamus-pituitary-adrenal axis, because a single pretreatment of SP extract
could rescue increased serum corticosterone and plasma adrenocorticotropin levels
induced by acute elevated platform stress. A single pretreatment of SP extract
could also elevate the mRNA expression of hippocampal glucocorticoid receptors.
In conclusion, our results suggest that SP extract may act as an anti-stress
medication to produce antidepressant-like effects.
PMID- 27608949
TI - Protective effects of paeoniflorin and albiflorin on chemotherapy-induced
myelosuppression in mice.
AB - Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in
traditional Chinese medicines (TCM). Two isomers, paeoniflorin (PF) and
albiflorin (AF), are isolated from P. lactiflora. The present study aimed to
investigate the protective effects of PF and AF on myelosuppression induced by
chemotherapy in mice and to explore the underlying mechanisms. The mouse
myelosuppression model was established by intraperitoneal (i.p.) injection of
cyclophosphamide (CP, 200 mg.kg(-1)). The blood cell counts were performed. The
thymus index and spleen index were also determined and bone morrow histological
examination was performed. The levels of tumor necrosis factor-alpha (TNF-alpha)
in serum and colony-stimulating factor (G-CSF) in plasma were measured by Enzyme
Linked Immunosorbent Assays (ELISA) and the serum levels of interleukin-3 (IL-3),
granulocyte-macrophagecolony-stimulatingfactor (GM-CSF), and interleukin-6 (IL-6)
were measured by radioimmunoassay (RIA). The levels of mRNA expression protein of
IL-3, GM-CSF and G-CSF in spleen and bone marrow cells were determined
respectively. PF and AF significantly increased the white blood cell (WBC) counts
and reversed the atrophy of thymus. They also increased the serum levels of GM
CSF and IL-3 and the plasma level of G-CSF and reduced the level of TNF-alpha in
serum. PF enhanced the mRNA level of IL-3 and AF enhanced the mRNA levels of GM
CSF and G-CSF in the spleen. PF and AF both increased the protein levels of GM
CSF and G-CSF in bone marrow cells. In conclusion, our results demonstrated that
PF and AF promoted the recovery of bone marrow hemopoietic function in the mouse
myelosuppression model.
PMID- 27608950
TI - Protease inhibitor in scorpion (Mesobuthus eupeus) venom prolongs the biological
activities of the crude venom.
AB - It is hypothesized that protease inhibitors play an essential role in survival of
venomous animals through protecting peptide/protein toxins from degradation by
proteases in their prey or predators. However, the biological function of
protease inhibitors in scorpion venoms remains unknown. In the present study, a
trypsin inhibitor was purified and characterized from the venom of scorpion
Mesobuthus eupeus, which enhanced the biological activities of crude venom
components in mice when injected in combination with crude venom. This protease
inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT
1 selectively inhibited trypsin with a Kivalue of 130 nmol.L(-1). Furthermore,
MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests,
MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting
that protease inhibitors in scorpion venom inhibited proteases and protect the
functionally important peptide/protein toxins from degradation, consequently
keeping them active longer. In conclusion, this was the first experimental
evidence about the natural existence of serine protease inhibitor in the venom of
scorpion Mesobuthus eupeus, which preserved the activity of venom components,
suggests that scorpions may use protease inhibitors for survival.
PMID- 27608951
TI - Biochemical synthesis of silver nanoprticles using filamentous fungi Penicillium
decumbens (MTCC-2494) and its efficacy against A-549 lung cancer cell line.
AB - Biosynthesis of silver and other metallic nanoparticles is one of the emerging
research area in the field of science and technology due to their potentiality,
especially in the field of nano-biotechnology and biomedical sciences in order to
develop nanomedicine. In our present study, Penicillium decumbens (MTCC-2494) was
brought from Institute of Microbial Technology (IMTECH) Chandigarh and employed
for extracellular biological synthesis of silver nanoparticles. Ag-NPs formation
was appeared with a dark brown color inside the conical flask. Characterization
of Ag-NPs were done by UV-Spectrophotometric analysis which showed absorption
peak at 430 nm determines the presence of nanoparticles, Fourier transform
infrared (FT-IR) spectroscopic analysis, showed amines and amides are the
possible proteins involved in the stabilization of nanoparticles as capping
agent. Atomic force Microscopy (AFM) confirmed the particle are spherical, size
was around 30 to 60 nm and also the roughness of nanoparticles. Field emission
scanning electron microscopy (FE-SEM) showed the topology of the nanoparticles
and were spherical in shape. The biosynthesis process was found fast, ecofriendly
and cost effective. Nano-silver particle was found to have a broad antimicrobial
activity and also it showed good enhancement of antimicrobial activity of
Carbenicillin, Piperacillin, Cefixime, Amoxicillin, Ofloxacin and Sparfloxacin in
a synergistic mode. These Ag-NPs showed good anti-cancer activity at 80 MUg.mL(
1)upon 24 hours of incubation and toxicity increases upon 48 hours of incubation
against A-549 human lung cancer cell line and the synergistic formulation of the
antibiotic with the synthesized nanoparticles was found more effective against
the pathogenic bacteria studied.
PMID- 27608952
TI - Novel 9, 10-dihydrophenanthrene derivatives from Eria bambusifolia with
cytotoxicity aganist human cancer cells in vitro.
AB - The present study was designed to identify bioactive compounds similar to those
isolated from Dendrobium genus from its relative specie Eria bambusifolia.
Compounds 1-10 were isolated and purified using silica gel, MCI CHP-20 gel,
Sephadex LH-20, and Lichroprep RP-18 chromatography methods. Their structures
were elucidated by means of extensive spectroscopic analyses. The cytotoxicity of
these compounds against five human cancer cell lines was tested. Erathrins A and
B (1 and 2) were new compounds, and compound 1 represented a novel carbon
framework having a phenanthrene-phenylpropane unit with a dioxane moiety.
Moreover, compound 1 showed selective cytotoxic activity against HL-60 cells
(IC50 = 14.50 MUmol.L(-1)). These results provided a basis for future development
of these agents as anticancer lead compounds.
PMID- 27608953
TI - Analysis of aristolochic acids, aristololactams and their analogues using liquid
chromatography tandem mass spectrometry.
AB - More than 80 aristolochic acids (AAs) and aristololactams (ALs) have been found
in plants of the Aristolochiaceae family, but relatively few have been fully
studied. The present study aimed at developing and validating a liquid
chromatography tandem mass spectrometry (LC/MS(n)) for the analysis of these
compounds. We characterized the fragmentation behaviors of 31 AAs, ALs, and their
analogues via high performance liquid chromatography coupled with electrospray
ionization mass spectrometry. We summarized their fragmentation rules and used
these rules to identify the constituents contained in Aristolochia contorta, Ar.
debilis, Ar. manshurensis, Ar. fangchi, Ar. cinnabarina, and Ar. mollissima. The
AAs and ALs showed very different MS behaviors. In MS(1) of AAs, the
characteristic pseudomolecular ions were [M + NH4](+), [M + H](+), and [M + H -
H2O](+). However, only [M + H](+) was found in the MS(1) of ALs, which was
simpler than that of AAs. Distinct MS(n)fragmentation patterns were found for AAs
and ALs, showing the same skeleton among the different substituent groups. The
distribution of the 31 constituents in the 6 species of Aristolochia genus was
reported for the first time. 25 Analogues of AAs and ALs were detected in this
genus. A hierarchical schemes and a calculating formula of the molecular formula
of these nitrophenanthrene carboxylic acids and their lactams were proposed. In
conclusion, this method could be applied to identification of similar unknown
constituents in other plants.
PMID- 27608954
TI - Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after
middle cerebral artery occlusion in mice.
AB - Loss of von Hippel-Lindau tumor suppressor protein (VHL) or hypoxia results in
nuclear relocalization of PDCD5 and subsequent mouse double minute 2 homolog
(Mdm2) degradation. Thus, VHL may involved in the PDCD5 mediated apoptosis and
autophagy after MCAO. In the present study, using PDCD5 knockout (PDCD5-/-) mice,
we aimed to demonstrate that knockout of PDCD5 gene could protect the brain from
ischemic injury by inhibiting the PDCD5-VHL pathway. 24h post MCAO surgery, PDCD5
gene knockout mice presented obvious improved brain blood flow, improved
neurological behavior and decreased cerebral infarction compared with wild type
mice. The levels of apoptotic and autophagic proteins were increased both in wild
type and PDCD5 knockout mice, whereas they were more pronounced in the wild type
mice. We observed decrease in the expression of VHL in wild type mice after MCAO.
Reduced expression of VHL may result in increased expression of hypoxia-inducible
factor 1alpha(HIF-1alpha) and (BCL2/adenovirus E1B 19kDa protein-interacting
protein 3) BNIP3. However, mice lacking PDCD5 had no changes in the expression of
VHL and have slighter increases in the expression of HIF-1alpha and BNIP3,
suggesting that PDCD5 may regulate apoptosis and autophagy through VHL-HIF-1alpha
BNIP3 pathway.
PMID- 27608955
TI - Overexpression of serum amyloid a 1 induces depressive-like behavior in mice.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of
memory and cognitive abilities. In AD, amyloid beta (Abeta) protein aggregates in
the brain of patients, forming amyloid plaques. Abeta plaques are known to be
surrounded by activated microglial cells. Serum amyloid A (SAA) is elevated from
several hundred to 1000-fold as part of the immune response against various
injuries, including trauma, infection, and inflammation. Additionally, continuous
elevation of SAA is related to the development of amyloidosis. This study was
designed to identify the relationship between SAA1 and AD using liver specific
SAA1 overexpressing mice (TG), because SAA1 is expressed in the liver during the
acute phase. We detected exogenous SAA1 expression in the brain of TG mice. This
result implies that liver-derived SAA1 migrates to the brain tissues. Thus, we
confirmed that the blood brain barrier (BBB) functioned normally using Evans-blue
staining and CARS. Furthermore, our results show an increase in the accumulation
of the 87kDa form of Abeta in TG mice compared to wild type mice (WT).
Additionally, the number of microglial cells and levels of pro-inflammatory
cytokines were increased. Next, we investigated the relationship between SAA1 and
depression by performing social interaction tests. The results showed that TG
mice have a tendency to avoid stranger mice and an impaired social recognition.
In conclusion, the SAA1 TG mouse model is a valuable model to study depression.
PMID- 27608956
TI - Interleukin-19 alleviates brain injury by anti-inflammatory effects in a mice
model of focal cerebral ischemia.
AB - Stroke causes brain injury with neuroinflammation which exacerbates the neuronal
damage. Recent studies show that anti-inflammatory cytokine interleukin-19 (IL
19) plays a critical part in the inflammatory and ischemic vascular diseases, yet
its potential role in ischemic stroke is unknown. Here, we tested the hypothesis
that IL-19 exerts protective effects against brain ischemia by modulating
inflammation after stroke. Mice were injected intraperitoneally with 10ng/g per
day recombinant mouse IL-19 starting pre-stroke, and were subjected to transient
middle cerebral artery occlusion. Infarct volume was assessed by
triphenyltetrazolium chloride and neurobehavioral outcome by neurological scores.
Inflammation was measured using real-time quantitative PCR, immunochemistry, and
fluorescence-activated cell sorting. Infarct volume at 72h after stroke was
significantly smaller in IL-19 treated group and focal neurological score was
significantly better. IL-19 treatment markedly attenuated elevation of the
expression of TNF-alpha and IL-6 mRNA, suppressed increases in the number of
microglia, macrophages, CD4+ T cells, CD8+ T cells as well as B cells, and
blocked activation of macrophages and neutrophils in the ischemic brain. In
peripheral blood, IL-19 injection helped to robustly preserve the reduced immune
cells, including macrophages, CD4+ T cells, CD8+ T cells and B cells, compared to
control group. IL-19 reduced brain infarction and attenuated neurological
deficits following stroke in mice, probably by inhibiting infiltration and
activation of immune cells, and by suppressing increases in gene expression of
proinflammatory cytokines. This may identify IL-19 as a new therapeutic to limit
neuroinflammation after stroke.
PMID- 27608957
TI - Angiotensin converting enzyme serum activities: Relationship with Alzheimer's
disease.
AB - OBJECTIVE: To determine serum activities of angiotensin-converting enzyme (ACE)
as a marker in diagnosis and determine the severity of Alzheimer's disease (AD),
METHODS: We measured serum ACE activities in 59 moderate-severe AD, 19 mild AD,
45 amnestic mild cognitive impairment (aMCI) and 39 controls. RESULTS: We found
that patients in moderate-severe AD stages showed significantly higher ACE in
comparison to aMCI and controls (ANOVA, LSD post hoc test: p: 0.02 and p: 0.01,
respectively). Logistic regression analysis showed that if ACE activities added
200 U/L, the superiority of AD risk was 1.18 times higher than before compared
with the control group (OR 1.18, 95% CI 1.01-1.74; P=0.49). By means of
multivariate linear regression analysis, we found that age (beta coefficient:
7.77; P: 0.01) was significantly associated with ACE activities. However, ACE
activities were found to be significantly negatively associated with measures of
orientation and immediate recall among the AD patients (r<0, P<0.05), whereas ACE
activities were not associated with any MMSE scores among the non-AD groups (P >
0.05).uuuu CONCLUSIONS: ACE serum activity that correlates with age is likely to
constitute a potential risk factor for the development of AD. ACE serum activity
might be a useful biomarker for disease status with increasingly high ACE from
mild stage to moderate-severe stage. Moreover, patients with aMCI could take ACE
inhibitor (ACEI) to decrease the incidence of AD, and patients with AD could take
ACEI to retard cognitive decline in early AD.
PMID- 27608958
TI - Modelling ADHD: A review of ADHD theories through their predictions for
computational models of decision-making and reinforcement learning.
AB - Attention deficit hyperactivity disorder (ADHD) is characterized by altered
decision-making (DM) and reinforcement learning (RL), for which competing
theories propose alternative explanations. Computational modelling contributes to
understanding DM and RL by integrating behavioural and neurobiological findings,
and could elucidate pathogenic mechanisms behind ADHD. This review of
neurobiological theories of ADHD describes predictions for the effect of ADHD on
DM and RL as described by the drift-diffusion model of DM (DDM) and a basic RL
model. Empirical studies employing these models are also reviewed. While theories
often agree on how ADHD should be reflected in model parameters, each theory
implies a unique combination of predictions. Empirical studies agree with the
theories' assumptions of a lowered DDM drift rate in ADHD, while findings are
less conclusive for boundary separation. The few studies employing RL models
support a lower choice sensitivity in ADHD, but not an altered learning rate. The
discussion outlines research areas for further theoretical refinement in the ADHD
field.
PMID- 27608959
TI - From science to technology: Orientation and mobility in blind children and
adults.
AB - The last quarter of a century has seen a dramatic rise of interest in the
development of technological solutions for visually impaired people. However,
despite the presence of many devices, user acceptance is low. Not only are
visually impaired adults not using these devices but they are also too complex
for children. The majority of these devices have been developed without
considering either the brain mechanisms underlying the deficit or the natural
ability of the brain to process information. Most of them use complex feedback
systems and overwhelm sensory, attentional and memory capacities. Here we review
the neuroscientific studies on orientation and mobility in visually impaired
adults and children and present the technological devices developed so far to
improve locomotion skills. We also discuss how we think these solutions could be
improved. We hope that this paper may be of interest to neuroscientists and
technologists and it will provide a common background to develop new science
driven technology, more accepted by visually impaired adults and suitable for
children with visual disabilities.
PMID- 27608960
TI - Differential mechanistic investigation of protective effects from imperatorin and
sec-O-glucosylhamaudol against arsenic trioxide-induced cytotoxicity in vitro.
AB - BACKGROUND AND PURPOSE: The clinical use of arsenic trioxide (As2O3) for treating
acute promyelocytic leukemia (APL) is limited due to its severe cardiotoxicity.
The possible mechanisms of As2O3-induced cardiotoxicity include DNA
fragmentation, reactive oxygen species (ROS) generation, cardiac ion channel
changes and apoptosis. The present study is designed to investigate the
protective effects of imperatorin and sec-O-glucosylhamaudol and to explore their
mechanistic involvement in As2O3-induced cytotoxicity. EXPERIMENTAL METHODS: Cell
viability assay, Lactate dehydrogenase (LDH) release, Acridine orange/ethidium
bromide (AO/EB) double staining, Caspase-3 activity assay, ROS generation,
cellular calcium levels, mRNA expression levels by qRT-PCR and protein expression
levels by Western blotting were measured in H9c2 cells in combination with As2O3
and imperatorin or sec-O-glucosylhamaudol. KEY RESULTS: We observed that H9c2
cells treated with imperatorin or sec-O-glucosylhamaudol were more resistant to
As2O3-induced cell death. Both imperatorin and sec-O-glucosylhamaudol reduced
H9c2 cell apoptosis, but both imperatorin and sec-O-glucosylhamaudol had no
effects on Caspase-3 activity and intracellular calcium accumulation.
Furthermore, imperatorin was capable of suppressing ROS generation, while sec-O
glucosylhamaudol did not show this effect. Moreover, imperatorin and sec-O
glucosylhamaudol triggered Nrf2 activation, which resulted in upregulation of
downstream phase II metabolic enzymes and antioxidant protein/enzyme, probably
offering cellular protection to As2O3-induced cardiotoxicity via the Nrf2 signal
pathway. CONCLUSIONS AND IMPLICATIONS: Imperatorin and sec-O-glucosylhamaudol can
ameliorate As2O3-induced cytotoxicity and apoptosis in H9c2 cells, the mechanisms
probably related to antioxidation. As2O3 in combination with imperatorin or sec-O
glucosylhamaudol could be considered as a novel strategy to expand the clinical
application of As2O3.
PMID- 27608961
TI - Deformed wing virus can be transmitted during natural mating in honey bees and
infect the queens.
AB - Deformed wing virus is an important contributor to honey bee colony losses.
Frequently queen failure is reported as a cause for colony loss. Here we examine
whether sexual transmission during multiple matings of queens is a possible way
of virus infection in queens. In an environment with high prevalence of deformed
wing virus, queens (n = 30) were trapped upon their return from natural mating
flights. The last drone's endophallus (n = 29), if present, was removed from the
mated queens for deformed wing virus quantification, leading to the detection of
high-level infection in 3 endophalli. After oviposition, viral quantification
revealed that seven of the 30 queens had high-level deformed wing virus
infections, in all tissues, including the semen stored in the spermathecae. Two
groups of either unmated queens (n = 8) with induced egg laying, or queens (n =
12) mated in isolation with drones showing comparatively low deformed wing virus
infections served as control. None of the control queens exhibited high-level
viral infections. Our results demonstrate that deformed wing virus infected
drones are competitive to mate and able to transmit the virus along with semen,
which occasionally leads to queen infections. Virus transmission to queens during
mating may be common and can contribute noticeably to queen failure.
PMID- 27608962
TI - Low-dose oral contraceptive-induced acute myocardial infarction.
AB - OBJECTIVES: Since their introduction, oral contraceptives (OCs) have been
associated with risk to both the venous and the arterial systems. Studies have
shown that OC use is associated with a risk of venous thromboembolism, ischaemic
stroke and acute myocardial infarction (MI). MI is rarely seen in patients using
OCs, particularly in the absence of clinical risk factors or smoking. CASE: We
report a case of acute inferior MI in a 20-year-old non-smoker who had used a low
dose OC (3 mg drospirenone and 30 MUg ethinyl estradiol) for 1 month. As far as
we know, this is the youngest case of acute MI associated with a low-dose OC.
CONCLUSION: Low-dose OCs may also be responsible for acute MI even in a very
young female without any cardiovascular risk factors. Therefore, the clinicians
should be aware of this mortal events during follow-up of the patient using OCs.
PMID- 27608963
TI - Bidirectional associations between psychosocial well-being and body mass index in
European children: longitudinal findings from the IDEFICS study.
AB - BACKGROUND: The negative impact of childhood overweight on psychosocial well
being has been demonstrated in a number of studies. There is also evidence that
psychosocial well-being may influence future overweight. We examined the
bidirectional association between childhood overweight and psychosocial well
being in children from a large European cohort. The dual aim was to investigate
the chronology of associations between overweight and psychosocial health
indicators and the extent to which these associations may be explained by
parental education. METHODS: Participants from the IDEFICS study were recruited
from eight countries between September 2007 and June 2008 when the children were
aged 2 to 9.9 years old. Children and families provided data on lifestyle,
psychosocial well-being, and measured anthropometry at baseline and at follow-up
2 years later. This study includes children with weight, height, and psychosocial
well-being measurements at both time points (n = 7,831). Psychosocial well-being
was measured by the KINDL(r) and Strengths and Difficulties Questionnaire
respectively. The first instrument measures health-related quality of life
including emotional well-being, self-esteem, parent relations and social
relations while the second measures well-being based on emotional symptoms,
conduct problems and peer-related problems. Logistic regression was used for
modeling longitudinal associations. RESULTS: Children who were overweight at
baseline had increased risk of poor health-related quality of life (odds ratio
(OR) = 1.23; 95 % confidence interval (CI):1.03-1.48) measured 2 years later;
this association was unidirectional. In contrast to health-related quality of
life, poor well-being at baseline was associated with increased risk of
overweight (OR = 1.39; 95 % CI:1.03-1.86) at 2 year follow-up; this association
was also only observed in one direction. Adjustment for parental education did
not change our findings. CONCLUSION: Our findings indicate that the association
between overweight and psychosocial well-being may be bidirectional but varies by
assessment measures. Future research should further investigate which aspects of
psychosocial well-being are most likely to precede overweight and which are more
likely to be consequences of overweight.
PMID- 27608964
TI - Attenuation of glycation-induced multiple protein modifications by Indian
antidiabetic plant extracts.
AB - CONTEXT: Protein glycation is the major contributing factor in the development of
diabetic complications. The antiglycation potential of medicinal plants provides
a promising opportunity as complementary interventions for complications.
OBJECTIVE: To investigate the antiglycation potential of 19 medicinal plants
extracts using albumin by estimating different indicators: (1) glycation (early
and late), (2) albumin oxidation, and (3) amyloid aggregation. MATERIALS AND
METHODS: The effect of aqueous plant extracts (1% w/v) on protein glycation was
assessed by incubating albumin (10 mg/mL) with fructose (250 mM) for 4 days.
Degree of protein glycation in the absence and presence of plant extracts was
assessed by estimating fructosamine, advanced glycation end products (AGEs),
carbonyls, free thiol group and beta-amyloid aggregation. RESULTS: Petroselinum
crispum, Boerhavia diffusa, Terminalia chebula, Swertia chirayita and Glycyrrhiza
glabra showed significant antiglycating activity. P. crispum and A. barbadensis
inhibited the carbonyl stress and protected the thiol group from oxidative
damage. There was significant correlation between protein thiols and amyloid
inhibition (R = -.69, p < .001). CONCLUSION: P. crispum, B. diffusa and T.
chebula had the most potent antiglycation activity. These plant exerted
noticeable antiglycation activity at different glycation modifications of
albumin. These findings are important for identifying plants with potential to
combat diabetic complications.
PMID- 27608965
TI - Mitosomal chaperone modulation during the life cycle of the pathogenic protist
Giardia intestinalis.
AB - The mitosome is a double-membrane enveloped organelle that is found in few
unicellular eukaryotes, one of which is the human intestinal parasitic protist
Giardia intestinalis, which also lacks mitochondria and peroxisomes. This
flagellated protist grows in vitro as trophozoites and under some conditions,
differentiates into cysts, which are characterized by the absence of externalized
flagella, a round shape, and the presence of a cyst wall. The presence and
distribution of mitosomal proteins, such as giardial iron-sulfur cluster protein
(GiIscU), heat-shock protein 70 (mit-HSP70) and giardial chaperonin 60 (GiCpn60),
during the process of trophozoite-to-cyst transformation was tracked using
confocal laser scanning microscopy and western blotting. During the early stages
of the differentiation process (~12h), there was a significant decrease in the
extent of chaperone labeling in the cells, which disappeared after 21h but was
recovered during the cyst stage; IscU labeling remained present throughout the
differentiation process. This finding was confirmed by mRNA expression analysis,
thus indicating that a process modulates the expression of mitosomal chaperones
during the G. intestinalis life cycle. Microscopy techniques, such as structured
illumination and electron tomography, revealed a novel profile for central
mitosomes, as well as the presence of both rounded and elongated mitosomes.
PMID- 27608966
TI - Insights into the process of EB1-dependent tip-tracking of kinesin-14 Ncd. The
role of the microtubule.
AB - End-binding proteins are capable of tracking the plus-ends of growing
microtubules (MTs). The motor protein Ncd, a member of the kinesin-14 family,
interacts with EB1 protein and becomes a non-autonomous tip-tracker. Here, we
attempted to find out whether at least for Ncd, the efficient EB1-mediated tip
tracking involves the interaction of the kinesin with the MT surface. We prepared
a series of Ncd tail mutants in which the MT-binding sites were altered or
eliminated. Using TIRF microscopy, we characterized their behavior as tip
trackers and measured the dwell times of single molecules of EB1 and Ncd tail or
its mutated forms. The mutated forms of Ncd tail exhibited tip-tracking in the
presence of EB1 and the effectiveness of this process was proportional to the
affinity of the mutant's tail to MT. Even though the interaction of Ncd with EB1
was weak (Kd~9MUM) the half saturating concentration of EB1 for tip-tracking was
7nM. The dwell time of Ncd tail in the presence of EB1 was ~1s. The dwell time of
EB1 alone was shorter (~0.3s) and increased considerably in the presence of a
large excess of Ncd tail. We demonstrated that tip-tracking of kinesin-14 occurs
through several concurrent mechanisms: binding of kinesin only to EB1 located at
the MT end, interaction of the kinesin molecules with a composite site formed by
EB1 and the MT tip, and probably surface diffusion of the tail along MT. The
second mechanism seems to play a crucial role in efficient tip-tracking.
PMID- 27608967
TI - Portugal and Angola: similarities and differences in Toxoplasma gondii
seroprevalence and risk factors in pregnant women.
AB - In this study we determined the presence of IgM/IgG antibodies to Toxoplasma
gondii in sera of 155 and 300 pregnant women from Lisbon (Portugal) and Luanda
(Angola), respectively, and evaluated the potential risk factors associated with
this infection. DNA detection was performed by PCR assays targeting T. gondii
regions (RE/B1). Overall, 21.9% (10.9% IgG, 10.9% IgG/IgM) of the Lisbon women
and 27.3% (23.7%, IgG, 2% IgM, 1.7% IgG/IgM) of the Luanda women had antibodies
to T. gondii. Single variable and binary logistic regression analyses were
conducted. Based on the latter, contacts with cats (family/friends), and having
more than two births were identified as risk factors for Toxoplasma infection in
Lisbon women. In Luanda, the risk factors for T. gondii infection suggested by
the single variable analysis (outdoor contact with cats and consumption of
pasteurized milk/dairy products) were not confirmed by binary logistic
regression. This study shows original data from Angola, and updated data from
Portugal in the study of infection by T. gondii in pregnant women, indicating
that the prevalence of anti-Toxoplasma antibodies is high enough to alert the
government health authorities and implement appropriate measures to control this
infection.
PMID- 27608968
TI - Congenital anomalies following use of isotretinoin: Emphasis on its legal
aspects.
AB - We described a neonate with severe and multiple abnormalities following use of
isotretinoin, in spite of the mother's previous knowledge of drug complications.
Initial physical examination after delivery showed congenital absence of both
eyes and both auricles as well as anal atresia and a cleft palate. Due to severe
respiratory distress and atresia of the anus, the neonate was admitted to a
neonatal intensive care unit and underwent reconstructive surgery. The drug
should not have been used during pregnancy. Using this drug within pregnancy with
awareness of its side effects may have legal consequences.
PMID- 27608970
TI - Measuring health burden without discriminating against the disabled.
AB - Background: measures of population health, like the Disability Adjusted Life Year
(DALY), are important for health policy and planning. Some worry, however, that
these measures discriminate against the disabled. Methods: This paper provides an
analysis of the disability discrimination problem. Then, adapting a fixed-plus
variable framework proposed in welfare economics to the case of health
measurement, it proposes a novel measure called the Ethically Adjusted Life Year
(EALY). Results: The EALY, in at least some formulations, can avoid
discriminating against the disabled. It is different from, and has some
advantages over, alternative ways of avoiding discrimination. Conclusions: There
is reason to consider using the EALY in measuring health burden and the impact of
health interventions.
PMID- 27608971
TI - Drop metastasis from hepatocellular carcinoma after percutaneous radiofrequency
ablation therapy.
PMID- 27608973
TI - Financial incentives for a healthy life style and disease prevention among older
people: a systematic literature review.
AB - BACKGROUND: To motivate people to lead a healthier life and to engage in disease
prevention, explicit financial incentives, such as monetary rewards for attaining
health-related targets (e.g. smoking cessation, weight loss or increased physical
activity) or disincentives for reverting to unhealthy habits, are applied. A
review focused on financial incentives for health promotion among older people is
lacking. Attention to this group is necessary because older people may respond
differently to financial incentives, e.g. because of differences in opportunity
costs and health perceptions. To outline how explicit financial incentives for
healthy lifestyle and disease prevention work among older persons, this study
reviews the recent evidence on this topic. METHODS: We applied the method of
systematic literature review and we searched in PUBMED, ECONLIT and COCHRANE
LIBRARY for studies focused on explicit financial incentives targeted at older
adults to promote health and stimulate primary prevention as well as screening.
The publications selected as relevant were analyzed based on directed
(relational) content analysis. The results are presented in a narrative manner
complemented with an appendix table that describes the study details. We assessed
the design of the studies reported in the publications in a qualitative manner.
We also checked the quality of our review using the PRISMA 2009 checklist.
RESULTS: We identified 15 studies on the role of explicit financial incentives in
changing health-related behavior of older people. They include both, quantitative
studies on the effectiveness of financial rewards as well as qualitative studies
on the acceptability of financial incentives. The quantitative studies are
characterized by a great diversity of designs and provide mixed results on the
effects of explicit financial incentives. The results of the qualitative studies
indicate limited trust of older people in the use of explicit financial
incentives for health promotion and prevention. CONCLUSIONS: More research is
needed on the effects of explicit financial incentives for prevention and
promotion among older people before their broader use can be recommended.
Overall, the design of the financial incentive system may be a crucial element in
their acceptability.
PMID- 27608972
TI - Placental growth factor: What hematologists need to know.
AB - Although first identified in placenta, the angiogenic factor known as placental
growth factor (PlGF) can be widely expressed in ischemic or damaged tissues.
Recent studies have indicated that PlGF is a relevant factor in the pathobiology
of blood diseases including hemoglobinopathies and hematologic malignancies.
Therapies for such blood diseases may one day be based upon these and ongoing
investigations into the role of PlGF in sickle cell disease, acute and chronic
leukemias, and complications related to hematopoietic cell transplantation. In
this review, we summarize recent studies regarding the potential role of PlGF in
blood disorders and suggest avenues for future research.
PMID- 27608974
TI - Detection and molecular characterization of porcine reproductive and respiratory
syndrome virus in Lithuanian wild boar populations.
AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is
recognized worldwide as an important and economically devastating pathogen in pig
production. Although PRRSV is widespread in domestic swine, there is a lack of
information regarding PRRSV infection in European wild boars (Sus scrofa).
Currently available information does not provide conclusive evidence that wild
boars are a reservoir of PRRSV. Nevertheless, wild boars may be likely to become
infected by domestic swine through occasional direct or indirect contact.
Furthermore, wild boars can act as a reservoir for infectious diseases of
domestic pigs. Therefore, the objectives of the present study were to determine
the virus prevalence and further explore the epidemiology and diversity of PRRSV
strains present in Lithuanian wild boars over a 5-year period. A total of 1597
tissue and serum samples from wild boars inhabiting 44 districts and ten counties
in Lithuania were analysed using conventional nested reverse transcription
polymerase chain reaction (RT-PCR) and real-time Taqman RT-PCR for the detection
of PRRSV-specific open reading frame (ORF) 1 and 6 sequences. RESULTS: PRRSV was
highly prevalent in Lithuanian wild boar populations, with an average rate of
18.66 % using conventional RT-PCR and 19.54 % using real-time RT-PCR. PRRSV was
detected in 36.71 and 41.77 % of 237 hunting grounds tested by conventional RT
nPCR and real-time RT-PCR, respectively. No statistically significant differences
in PRRSV prevalence were observed by geographic area in the ten Lithuanian
counties. Animals infected with PRRSV were identified in all age groups; however,
significantly higher prevalence rates were identified in subadult and adult wild
boars than in juveniles up to 12 months old. No positive results were obtained
using conventional PCR with Type 2 specific primers. Phylogenetic analysis of the
partial ORF5 region revealed that ten wild boars harboured virus sequences
belonging to genetic subtypes 3 and 4 and may therefore pose a serious threat to
Lithuanian pig farms in which only subtype two strains are circulating.
CONCLUSIONS: The results of virus prevalence and phylogenetic analyses strongly
support the role of wild boars as a possible natural reservoir for PRRSV in
Lithuania.
PMID- 27608975
TI - Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide
in a large cohort of systemic sclerosis patients.
AB - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by
progressive fibrosis of the skin and the internal organs. In a previous work we
suggested a correlation between levels of salivary psoriasin (S100A7) and
pulmonary involvement in SSc patients. The goals of this study are to determine
the distribution characteristics of psoriasin in whole saliva (WS) of SSc and
healthy donor populations and define its predictive value on diffusion capacity
of carbon monoxide (DLCO), along with others clinical parameters. METHODS:
Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63
Raynaud syndrome patients, 40 patients affected by other connective diseases (non
case) and 74 healthy control subjects. RESULTS: A significant increase of
salivary psoriasin was observed in SSc patients when compared with other healthy
and pathological controls. Moreover, we confirmed the efficacy of salivary
psoriasin to correlate with DLCO in a large cohort of SSc patients. CONCLUSIONS:
Overall our results suggest a rapid, non invasive and low costing method which
can help clinicians in the evaluation of SSc pulmonary involvement.
PMID- 27608976
TI - Financial protection of rural health insurance for patients with hypertension and
diabetes: repeated cross-sectional surveys in rural China.
AB - BACKGROUND: The New Cooperative Medical Scheme (NCMS) in rural China has been
expanding in both population coverage and benefit package. China has also
established an essential medicine policy in recent years to further reduce
patients' medical expenditures and financial burden. This study aims to evaluate
the impact of these policies on reducing medical expenditures and financial
burden of patients diagnosed with hypertension and diabetes. METHODS: This study
used repeated cross-sectional surveys in 2011 and 2012 in three counties of
Shandong Province. Outpatient and inpatient service expenditures and catastrophic
health expenditures (CHE) were measured and analyzed. RESULTS: Medical
expenditures for outpatient services significantly increased for hypertensive and
diabetic patients within a 1 year period, while inpatient service expenditures
remained unchanged. Although NCMS increased its reimbursement rate, hypertensive
and diabetic patients still heavily suffered CHE from both outpatient and
inpatient services. Outpatient services were more important factors than
inpatient services contributing to non-communicable chronic diseases (NCD)
patients' financial burden. CONCLUSIONS: The effects of NCMS expansion have been
offset by the rapid escalation of medical expenditures. More attention should be
paid to the design of NCMS benefit package to cover NCD outpatient services.
There is also an urgent need to reform the current Fee for Service to other
provider payment methods in order to control the escalating NCD medical
expenditures.
PMID- 27608977
TI - Deferoxamine pre-treatment protects against postoperative cognitive dysfunction
of aged rats by depressing microglial activation via ameliorating iron
accumulation in hippocampus.
AB - Postoperative cognitive dysfunction (POCD) is a common complication of elderly
patients after surgery. The mechanisms of POCD have not been clarified. Iron
accumulation is a feature of neurodegeneration. Recent reports showed that iron
content was increased with impaired cognition induced by surgery. We sought to
investigate whether iron chelation would attenuate POCD. In this study, male aged
(18 months) Sprague-Dawley rats received 100 mg/kg deferoxamine or saline
solution (0.9%) for 6 days before exploratory laparotomy. Cognition was evaluated
by Morris water maze before and after surgery. Additional rats received
deferoxamine or saline were used to determine hippocampal iron content, iron
transport-related proteins (transferrin receptor, divalent metal transporter 1,
ferroportin 1 and hepcidin), oxidative stress, microglial activation and brain
cell apoptosis. It was found that deferoxamine improved postoperative spatial
memory in aged rats. Deferoxamine significantly reduced hippocampal iron
concentration and ferritin. Surgery increased divalent metal transporter 1 and
hepcidin, decreased transferrin receptor and ferroportin 1, and enhanced
ferroportin 1 mRNA. However, deferoxamine reversed the changes of these proteins.
Furthermore, deferoxamine sharply reduced the hippocampal reactive oxygen
species, malondialdehyde concentration and OX-42 that is a marker of microglia,
which might reduce postoperative brain cell apoptosis. This study showed that
deferoxamine may improve postoperative cognition of aged rats by ameliorating
oxidative stress induced by hippocampal iron accumulation, microglial activation
and brain cell apoptosis. This study suggests a potential therapeutic method for
reducing POCD.
PMID- 27608979
TI - Pediatric acute gastroenteritis: understanding caregivers' experiences and
information needs.
AB - OBJECTIVES: Pediatric acute gastroenteritis (AGE) is a common condition with high
health care utilization, persistent practice variation, and substantial family
burden. An initial approach to resolve these issues is to understand the
patient/caregiver experience of this illness. The objective of this study was to
describe caregivers' experiences of pediatric AGE and identify their information
needs, preferences, and priorities. METHODS: A qualitative, descriptive study was
conducted. Caregivers of a child with AGE were recruited for this study in the
pediatric emergency department (ED) at a tertiary hospital in a major urban
centre. Individual interviews were conducted (n=15), and a thematic analysis of
interview transcripts was completed using a hybrid inductive/deductive approach.
RESULTS: Five major themes were identified and described: 1) caregiver management
strategies; 2) reasons for going to the ED; 3) treatment and management of AGE in
the ED; 4) caregivers' information needs; and 5) additional factors influencing
caregivers' experiences and decision-making. A number of subthemes within each
major theme were identified and described. CONCLUSIONS: This qualitative
descriptive study has identified caregiver information needs, preferences, and
priorities regarding pediatric AGE. This study also identified inconsistencies in
the treatment and management of pediatric AGE at home and in the ED that
influence health care utilization and patient outcomes related to pediatric AGE.
PMID- 27608978
TI - Effect of provision of an integrated neonatal survival kit and early cognitive
stimulation package by community health workers on developmental outcomes of
infants in Kwale County, Kenya: study protocol for a cluster randomized trial.
AB - BACKGROUND: Each year, more than 200 million children under the age of 5 years,
almost all in low- and middle-income countries (LMICs), fail to achieve their
developmental potential. Risk factors for compromised development often coexist
and include inadequate cognitive stimulation, poverty, nutritional deficiencies,
infection and complications of being born low birthweight and/or premature.
Moreover, many of these risk factors are closely associated with newborn
morbidity and mortality. As compromised development has significant implications
on human capital, inexpensive and scalable interventions are urgently needed to
promote neurodevelopment and reduce risk factors for impaired development.
METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of
volunteer community health workers delivering either an integrated neonatal
survival kit, an early stimulation package, or a combination of both
interventions, to pregnant women during their third trimester of pregnancy,
compared to the current standard of care in Kwale County, Kenya. The neonatal
survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean
plastic sheet, surgical gloves and hand soap), sunflower oil emollient,
chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant
heater. Community health workers are also equipped with a portable hand-held
electric scale. The early cognitive stimulation package focuses on enhancing
caregiver practices by teaching caregivers three key messages that comprise
combining a gentle touch with making eye contact and talking to children,
responsive feeding and caregiving, and singing. The primary outcome measure is
child development at 12 months of age assessed with the Protocol for Child
Monitoring (Infant and Toddler version). The main secondary outcome is newborn
mortality. DISCUSSION: This study will provide evidence on effectiveness of
delivering an innovative neonatal survival kit and/or early stimulation package
to pregnant women in Kwale County, Kenya. Study findings will help inform policy
on the most appropriate interventions for promoting healthy brain development and
reduction of newborn morbidity and mortality in Kenya and other similar settings.
TRIAL REGISTRATION: ClinicalTrial.gov NCT02208960 (August 1, 2014).
PMID- 27608981
TI - Communication: Molecular gears.
AB - The (1)H nuclear magnetic resonance spectrum of hexamethylbenzene orientationally
ordered in the nematic liquid crystal ZLI-1132 is analysed using covariance
matrix adaptation evolution strategy. The spectrum contains over 350 000 lines
with many overlapping transitions, from which four independent direct dipolar
couplings are obtained. The rotations of the six methyl groups appear to be
correlated due to mutual steric hindrance. Adjacent methyl groups show counter
rotating or geared motion. Hexamethylbenzene thus behaves as a molecular
hexagonal gear.
PMID- 27608982
TI - Communication: Tunnelling splitting in the phosphine molecule.
AB - Splitting due to tunnelling via the potential energy barrier has played a
significant role in the study of molecular spectra since the early days of
spectroscopy. The observation of the ammonia doublet led to attempts to find a
phosphine analogous, but these have so far failed due to its considerably higher
barrier. Full dimensional, variational nuclear motion calculations are used to
predict splittings as a function of excitation energy. Simulated spectra suggest
that such splittings should be observable in the near infrared via overtones of
the nu2 bending mode starting with 4nu2.
PMID- 27608980
TI - Treatment with Rhus tripartita extract curtails isoproterenol-elicited
cardiotoxicity and oxidative stress in rats.
AB - BACKGROUND: Consumption of plant-derived nutraceuticals and crude drugs in
traditional medicine is widely believed to confer beneficial effects in thwarting
the progression of cardiovascular diseases. Rhus tripartita (family
Anacardiaceae) has been traditionally used to treat a wide range of ailments.
METHODS: In the present study we investigated the protective effects of an
alcoholic extract of the stem part of Rhus tripartita male genotype (RTSM) on
experimentally induced myocardial injury in rats. To this end, cardiac injury was
induced by administration of isoproterenol (ISO) and serum enzyme markers, lipid
profiles and cardiac tissue redox status were determined following RTSM treatment
(250 and 500 mg/kg). RESULTS: As a result, RTSM treatment significantly mitigated
ISO-triggered upregulation of cardiac-specific markers of injury creatine kinase
and lactate dehydrogenase. RTSM treatment significantly attenuated ISO-induced
increase in serum cholesterol and triglycerides as well alterations in serum
lipoproteins. Determination of oxidative balance showed that RTSM treatment
significantly blunted ISO-induced increase in malondialdehyde and decrease in
nonprotein sulfhydryl in cardiac tissue. Six compounds were isolated and
identified as gallocatechin 1, taxifolin 2, myricetin-3-O-beta-glucoside 3,
catechin 4, epicatechin 5, and 3',8-binaringenin 6. Compound 6 was isolated for
the first time from the stem part of Rhus tripartita. Furthermore, RTSM treatment
enhanced the survival fraction of cardiac cells exposed to oxidative stress in
vitro. CONCLUSION: We conclude that the antioxidant properties of RTSM treatment
underpin its cardioprotective pharmacological effects, thus, providing biological
evidence for the treatment of cardiovascular diseases using Rhus tripartita in
indigenous medicine.
PMID- 27608983
TI - Time-dependent density functional theory (TD-DFT) coupled with reference
interaction site model self-consistent field explicitly including spatial
electron density distribution (RISM-SCF-SEDD).
AB - Theoretical approach to design bright bio-imaging molecules is one of the most
progressing ones. However, because of the system size and computational accuracy,
the number of theoretical studies is limited to our knowledge. To overcome the
difficulties, we developed a new method based on reference interaction site model
self-consistent field explicitly including spatial electron density distribution
and time-dependent density functional theory. We applied it to the calculation of
indole and 5-cyanoindole at ground and excited states in gas and solution phases.
The changes in the optimized geometries were clearly explained with resonance
structures and the Stokes shift was correctly reproduced.
PMID- 27608984
TI - Recovering hidden dynamical modes from the generalized Langevin equation.
AB - In studying large molecular systems, insights can better be extracted by
selecting a limited number of physical quantities for analysis rather than
treating every atomic coordinate in detail. Some information may, however, be
lost by projecting the total system onto a small number of coordinates. For such
problems, the generalized Langevin equation (GLE) is shown to provide a useful
framework to examine the interaction between the observed variables and their
environment. Starting with the GLE obtained from the time series of the observed
quantity, we perform a transformation to introduce a set of variables that
describe dynamical modes existing in the environment. The introduced variables
are shown to effectively recover the essential information of the total system
that appeared to be lost by the projection.
PMID- 27608985
TI - Rate-equation modelling and ensemble approach to extraction of parameters for
viral infection-induced cell apoptosis and necrosis.
AB - We develop a theoretical approach that uses physiochemical kinetics modelling to
describe cell population dynamics upon progression of viral infection in cell
culture, which results in cell apoptosis (programmed cell death) and necrosis
(direct cell death). Several model parameters necessary for computer simulation
were determined by reviewing and analyzing available published experimental data.
By comparing experimental data to computer modelling results, we identify the
parameters that are the most sensitive to the measured system properties and
allow for the best data fitting. Our model allows extraction of parameters from
experimental data and also has predictive power. Using the model we describe
interesting time-dependent quantities that were not directly measured in the
experiment and identify correlations among the fitted parameter values. Numerical
simulation of viral infection progression is done by a rate-equation approach
resulting in a system of "stiff" equations, which are solved by using a novel
variant of the stochastic ensemble modelling approach. The latter was originally
developed for coupled chemical reactions.
PMID- 27608986
TI - Free-end adaptive nudged elastic band method for locating transition states in
minimum energy path calculation.
AB - A free-end adaptive nudged elastic band (FEA-NEB) method is presented for finding
transition states on minimum energy paths, where the energy barrier is very
narrow compared to the whole paths. The previously proposed free-end nudged
elastic band method may suffer from convergence problems because of the kinks
arising on the elastic band if the initial elastic band is far from the minimum
energy path and weak springs are adopted. We analyze the origin of the formation
of kinks and present an improved free-end algorithm to avoid the convergence
problem. Moreover, by coupling the improved free-end algorithm and an adaptive
strategy, we develop a FEA-NEB method to accurately locate the transition state
with the elastic band cut off repeatedly and the density of images near the
transition state increased. Several representative numerical examples, including
the dislocation nucleation in a penta-twinned nanowire, the twin boundary
migration under a shear stress, and the cross-slip of screw dislocation in face
centered cubic metals, are investigated by using the FEA-NEB method. Numerical
results demonstrate both the stability and efficiency of the proposed method.
PMID- 27608987
TI - Angle-dependent strong-field molecular ionization rates with tuned range
separated time-dependent density functional theory.
AB - Strong-field ionization and the resulting electronic dynamics are important for a
range of processes such as high harmonic generation, photodamage, charge
resonance enhanced ionization, and ionization-triggered charge migration.
Modeling ionization dynamics in molecular systems from first-principles can be
challenging due to the large spatial extent of the wavefunction which stresses
the accuracy of basis sets, and the intense fields which require non-perturbative
time-dependent electronic structure methods. In this paper, we develop a time
dependent density functional theory approach which uses a Gaussian-type orbital
(GTO) basis set to capture strong-field ionization rates and dynamics in atoms
and small molecules. This involves propagating the electronic density matrix in
time with a time-dependent laser potential and a spatial non-Hermitian complex
absorbing potential which is projected onto an atom-centered basis set to remove
ionized charge from the simulation. For the density functional theory (DFT)
functional we use a tuned range-separated functional LC-PBE*, which has the
correct asymptotic 1/r form of the potential and a reduced delocalization error
compared to traditional DFT functionals. Ionization rates are computed for
hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies,
intensities, and polarizations (angle-dependent ionization), and the results are
shown to quantitatively agree with time-dependent Schrodinger equation and strong
field approximation calculations. This tuned DFT with GTO method opens the door
to predictive all-electron time-dependent density functional theory simulations
of ionization and ionization-triggered dynamics in molecular systems using tuned
range-separated hybrid functionals.
PMID- 27608988
TI - Coupled wave equations theory of surface-enhanced femtosecond stimulated Raman
scattering.
AB - We present a coupled wave semiclassical theory to describe plasmonic enhancement
effects in surface-enhanced femtosecond stimulated Raman scattering (SE-FSRS). A
key result is that the plasmon enhanced fields which drive the vibrational
equation of motion for each normal mode results in dispersive lineshapes in the
SE-FSRS spectrum. This result, which reproduces experimental lineshapes,
demonstrates that plasmon-enhanced stimulated Raman methods provide unique
sensitivity to a plasmonic response. Our derived SE-FSRS theory shows a plasmonic
enhancement of |gpu|(2)ImchiR(omega)gst (2)/ImchiR(omega), where |gpu|(2) is the
absolute square of the plasmonic enhancement from the Raman pump, chiR(omega) is
the Raman susceptibility, and gst is the plasmonic enhancement of the Stokes
field in SE-FSRS. We conclude with a discussion on potential future experimental
and theoretical directions for the field of plasmonically enhanced coherent Raman
scattering.
PMID- 27608989
TI - An automated nudged elastic band method.
AB - A robust, efficient, dynamic, and automated nudged elastic band (AutoNEB)
algorithm to effectively locate transition states is presented. The strength of
the algorithm is its ability to use fewer resources than the nudged elastic band
(NEB) method by focusing first on converging a rough path before improving upon
the resolution around the transition state. To demonstrate its efficiency, it has
been benchmarked using a simple diffusion problem and a dehydrogenation reaction.
In both cases, the total number of force evaluations used by the AutoNEB method
is significantly less than the NEB method. Furthermore, it is shown that for a
fast and robust relaxation to the transition state, a climbing image elastic band
method where the full spring force, rather than only the component parallel to
the local tangent to the path, is preferred especially for pathways through
energy landscapes with multiple local minima. The resulting corner cutting does
not affect the accuracy of the transition state as long as this is located with
the climbing image method. Finally, a number of pitfalls often encountered while
locating the true transition state of a reaction are discussed in terms of
systematically exploring the multidimensional energy landscape of a given
process.
PMID- 27608990
TI - Wave propagation in spatially modulated tubes.
AB - We investigate wave propagation in rotationally symmetric tubes with a periodic
spatial modulation of cross section. Using an asymptotic perturbation analysis,
the governing quasi-two-dimensional reaction-diffusion equation can be reduced
into a one-dimensional reaction-diffusion-advection equation. Assuming a weak
perturbation by the advection term and using projection method, in a second step,
an equation of motion for traveling waves within such tubes can be derived. Both
methods predict properly the nonlinear dependence of the propagation velocity on
the ratio of the modulation period of the geometry to the intrinsic width of the
front, or pulse. As a main feature, we observe finite intervals of propagation
failure of waves induced by the tube's modulation and derive an analytically
tractable condition for their occurrence. For the highly diffusive limit, using
the Fick-Jacobs approach, we show that wave velocities within modulated tubes are
governed by an effective diffusion coefficient. Furthermore, we discuss the
effects of a single bottleneck on the period of pulse trains. We observe period
changes by integer fractions dependent on the bottleneck width and the period of
the entering pulse train.
PMID- 27608991
TI - Computing dispersive, polarizable, and electrostatic shifts of excitation energy
in supramolecular systems: PTCDI crystal.
AB - The gas-to-crystal-shift denotes the shift of electronic excitation energies,
i.e., the difference between ground and excited state energies, for a molecule
transferred from the gas to the bulk phase. The contributions to the gas-to
crystal-shift comprise electrostatic as well as inductive polarization and
dispersive energy shifts of the molecular excitation energies due to interaction
with environmental molecules. For the example of 3,4,9,10-perylene
tetracarboxylic-diimide (PTCDI) bulk, the contributions to the gas-to-crystal
shift are investigated. In the present work, electrostatic interaction is
calculated via Coulomb interaction of partial charges while inductive and
dispersive interactions are obtained using respective sum over states
expressions. The coupling of higher transition densities for the first 4500
excited states of PTCDI was computed using transition partial charges based on an
atomistic model of PTCDI bulk obtained from molecular dynamics simulations. As a
result it is concluded that for the investigated model system of a PTCDI crystal,
the gas to crystal shift is dominated by dispersive interaction.
PMID- 27608992
TI - Reverse Mossbauer effect as a possible source of "hot" molecules absorbed in
crystalline solids at low temperature.
AB - As an attempt to explain some of the many anomalies and unresolved problems which
have been reported about the dynamic behavior of particles and molecules absorbed
in crystalline solids, the "reverse Mossbauer effect" (RME) is proposed. RME
theory posits that a particle in non-equilibrium state with respect to a crystal
(colliding with the crystal or absorbed in it, but set out of thermal equilibrium
by some external cause) is scattered by the whole crystal with a momentum
proportional to a vector representing a reciprocal lattice point. The scattering
is expected to occur with a well-defined probability and the momentum
transferable to the particle is expected to follow a predictable distribution.
The RME theory, in practice, is an extension of the Bragg-von Laue scattering law
to high-energy colliding particles, in general, and can be applied to any
particle or molecule colliding with the surface of a crystalline solid or
absorbed in it, but not in thermal equilibrium with the crystal lattice. We
verified the RME theory by considering a well-defined unresolved problem. In an
experimental study about methane adsorbed in the zeolite Na-ZSM-5 [H. Jobic,
Chem. Phys. Lett. 170, 217 (1990)] reporting neutron inelastic-scattering spectra
(recoiled bands) at 10 K, the translational kinetic energy of methane resulted to
be much higher than equilibrium expected value, namely, about 85 K (or 7.3 meV).
The author concluded that "the interpretation of this unusual behavior has yet to
be found." In the present study, on the basis of the RME, an explanation of this
behavior is put forward.
PMID- 27608993
TI - Motif analysis for small-number effects in chemical reaction dynamics.
AB - The number of molecules involved in a cell or subcellular structure is sometimes
rather small. In this situation, ordinary macroscopic-level fluctuations can be
overwhelmed by non-negligible large fluctuations, which results in drastic
changes in chemical-reaction dynamics and statistics compared to those observed
under a macroscopic system (i.e., with a large number of molecules). In order to
understand how salient changes emerge from fluctuations in molecular number, we
here quantitatively define small-number effect by focusing on a "mesoscopic"
level, in which the concentration distribution is distinguishable both from micro
and macroscopic ones and propose a criterion for determining whether or not such
an effect can emerge in a given chemical reaction network. Using the proposed
criterion, we systematically derive a list of motifs of chemical reaction
networks that can show small-number effects, which includes motifs showing
emergence of the power law and the bimodal distribution observable in a
mesoscopic regime with respect to molecule number. The list of motifs provided
herein is helpful in the search for candidates of biochemical reactions with a
small-number effect for possible biological functions, as well as for designing a
reaction system whose behavior can change drastically depending on molecule
number, rather than concentration.
PMID- 27608994
TI - A generalized theoretical framework for the description of spin decoupling in
solid-state MAS NMR: Offset effect on decoupling performance.
AB - We present a generalized theoretical framework that allows the approximate but
rapid analysis of residual couplings of arbitrary decoupling sequences in solid
state NMR under magic-angle spinning conditions. It is a generalization of the
tri-modal Floquet analysis of TPPM decoupling [Scholz et al., J. Chem. Phys. 130,
114510 (2009)] where three characteristic frequencies are used to describe the
pulse sequence. Such an approach can be used to describe arbitrary periodic
decoupling sequences that differ only in the magnitude of the Fourier
coefficients of the interaction-frame transformation. It allows a ~100 times
faster calculation of second-order residual couplings as a function of pulse
sequence parameters than full spin-dynamics simulations. By comparing the
theoretical calculations with full numerical simulations, we show the potential
of the new approach to examine the performance of decoupling sequences. We
exemplify the usefulness of this framework by analyzing the performance of
commonly used high-power decoupling sequences and low-power decoupling sequences
such as amplitude-modulated XiX (AM-XiX) and its super-cycled variant SC-AM-XiX.
In addition, the effect of chemical-shift offset is examined for both high- and
low-power decoupling sequences. The results show that the cross-terms between the
dipolar couplings are the main contributions to the line broadening when offset
is present. We also show that the SC-AM-XIX shows a better offset compensation.
PMID- 27608995
TI - Handling the influence of chemical shift in amplitude-modulated heteronuclear
dipolar recoupling solid-state NMR.
AB - We present a theoretical analysis of the influence of chemical shifts on
amplitude-modulated heteronuclear dipolar recoupling experiments in solid-state
NMR spectroscopy. The method is demonstrated using the Rotor Echo Short Pulse
IRrAdiaTION mediated Cross-Polarization ((RESPIRATION)CP) experiment as an
example. By going into the pulse sequence rf interaction frame and employing a
quintuple-mode operator-based Floquet approach, we describe how chemical shift
offset and anisotropic chemical shift affect the efficiency of heteronuclear
polarization transfer. In this description, it becomes transparent that the main
attribute leading to non-ideal performance is a fictitious field along the rf
field axis, which is generated from second-order cross terms arising mainly
between chemical shift tensors and themselves. This insight is useful for the
development of improved recoupling experiments. We discuss the validity of this
approach and present quaternion calculations to determine the effective resonance
conditions in a combined rf field and chemical shift offset interaction frame
transformation. Based on this, we derive a broad-banded version of the
(RESPIRATION)CP experiment. The new sequence is experimentally verified using
SNNFGAILSS amyloid fibrils where simultaneous (15)N -> (13)CO and (15)N ->
(13)Calpha coherence transfer is demonstrated on high-field NMR instrumentation,
requiring great offset stability.
PMID- 27608996
TI - Ferromagnetic bond of Li10 cluster: An alternative approach in terms of effective
ferromagnetic sites.
AB - In this work, a model to explain the unusual stability of atomic lithium clusters
in their highest spin multiplicity is presented and used to describe the
ferromagnetic bonding of high-spin Li10 and Li8 clusters. The model associates
the (lack of-)fitness of Heisenberg Hamiltonian with the degree of (de
)localization of the valence electrons in the cluster. It is shown that a regular
Heisenberg Hamiltonian with four coupling constants cannot fully explain the
energy of the different spin states. However, a more simple model in which
electrons are located not at the position of the nuclei but at the position of
the attractors of the electron localization function succeeds in explaining the
energy spectrum and, at the same time, explains the ferromagnetic bond found by
Shaik using arguments of valence bond theory. In this way, two different points
of view, one more often used in physics, the Heisenberg model, and the other in
chemistry, valence bond, come to the same answer to explain those atypical bonds.
PMID- 27608997
TI - Fragmentation network of doubly charged methionine: Interpretation using graph
theory.
AB - The fragmentation of doubly charged gas-phase methionine (HO2CCH(NH2)CH2CH2SCH3)
is systematically studied using the self-consistent charge density functional
tight-binding molecular dynamics (MD) simulation method. We applied graph theory
to analyze the large number of the calculated MD trajectories, which appears to
be a highly effective and convenient means of extracting versatile information
from the large data. The present theoretical results strongly concur with the
earlier studied experimental ones. Essentially, the dication dissociates into
acidic group CO2H and basic group C4NSH10. The former may carry a single or no
charge and stays intact in most cases, whereas the latter may hold either a
single or a double charge and tends to dissociate into smaller fragments. The
decay of the basic group is observed to follow the Arrhenius law. The
dissociation pathways to CO2H and C4NSH10 and subsequent fragmentations are also
supported by ab initio calculations.
PMID- 27608998
TI - Anharmonic exciton dynamics and energy dissipation in liquid water from two
dimensional infrared spectroscopy.
AB - Water's extended hydrogen-bond network results in rich and complex dynamics on
the sub-picosecond time scale. In this paper, we present a comprehensive analysis
of the two-dimensional infrared (2D IR) spectrum of O-H stretching vibrations in
liquid H2O and their interactions with bending and intermolecular vibrations. By
exploring the dependence of the spectrum on waiting time, temperature, and laser
polarization, we refine our molecular picture of water's complex ultrafast
dynamics. The spectral evolution following excitation of the O-H stretching
resonance reveals vibrational dynamics on the 50-300 fs time scale that are
dominated by intermolecular delocalization. These O-H stretch excitons are a
result of the anharmonicity of the nuclear potential energy surface that arises
from the hydrogen-bonding interaction. The extent of O-H stretching excitons is
characterized through 2D depolarization measurements that show spectrally
dependent delocalization in agreement with theoretical predictions. Furthermore,
we show that these dynamics are insensitive to temperature, indicating that the
exciton dynamics alone set the important time scales in the system. Finally, we
study the evolution of the O-H stretching mode, which shows highly non-adiabatic
dynamics suggestive of vibrational conical intersections. We argue that the so
called heating, commonly observed within ~1 ps in nonlinear IR spectroscopy of
water, is a nonequilibrium state better described by a kinetic temperature rather
than a Boltzmann distribution. Our conclusions imply that the collective nature
of water vibrations should be considered in describing aqueous solvation.
PMID- 27608999
TI - Rate theory of solvent exchange and kinetics of Li(+) - BF4 (-)/PF6 (-) ion pairs
in acetonitrile.
AB - In this paper, we describe our efforts to apply rate theories in studies of
solvent exchange around Li(+) and the kinetics of ion pairings in lithium-ion
batteries (LIBs). We report one of the first computer simulations of the exchange
dynamics around solvated Li(+) in acetonitrile (ACN), which is a common solvent
used in LIBs. We also provide details of the ion-pairing kinetics of Li(+)-[BF4]
and Li(+)-[PF6] in ACN. Using our polarizable force-field models and employing
classical rate theories of chemical reactions, we examine the ACN exchange
process between the first and second solvation shells around Li(+). We calculate
exchange rates using transition state theory and weighted them with the
transmission coefficients determined by the reactive flux, Impey, Madden, and
McDonald approaches, and Grote-Hynes theory. We found the relaxation times
changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li(+)-[BF4] and Li(+)
[PF6] ion pairs, respectively. These results confirm that the solvent response to
the kinetics of ion pairing is significant. Our results also show that, in
addition to affecting the free energy of solvation into ACN, the anion type also
should significantly influence the kinetics of ion pairing. These results will
increase our understanding of the thermodynamic and kinetic properties of LIB
systems.
PMID- 27609000
TI - The structure of molten CuCl: Reverse Monte Carlo modeling with high-energy X-ray
diffraction data and molecular dynamics of a polarizable ion model.
AB - The results of the structural properties of molten copper chloride are reported
from high-energy X-ray diffraction measurements, reverse Monte Carlo modeling
method, and molecular dynamics simulations using a polarizable ion model. The
simulated X-ray structure factor reproduces all trends observed experimentally,
in particular the shoulder at around 1 A(-1) related to intermediate range
ordering, as well as the partial copper-copper correlations from the reverse
Monte Carlo modeling, which cannot be reproduced by using a simple rigid ion
model. It is shown that the shoulder comes from intermediate range copper-copper
correlations caused by the polarized chlorides.
PMID- 27609001
TI - The origin of the conductivity maximum in molten salts. II. SnCl2 and HgBr2.
AB - The phenomenon of electrical conductivity maxima of molten salts versus
temperature during orthobaric (closed-vessel) conditions is further examined via
ab initio simulations. Previously, in a study of molten BiCl3, a new theory was
offered in which the conductivity falloff at high temperatures is due not to
traditional ion association, but to a rise in the activation energy for atomic
ions hopping from counterion to counterion. Here this theory is further tested on
two more inorganic melts which exhibit conductivity maxima: another high
conducting melt (SnCl2, sigmamax = 2.81 Omega(-1) cm(-1)) and a low-conducting
one (HgBr2, sigmamax = 4.06 * 10(-4) Omega(-1) cm(-1)). First, ab initio
molecular dynamics simulations were performed and again appear successful in
reproducing the maxima for both these liquids. Second, analysis of the simulated
liquid structure (radial distributions, species concentrations) was performed. In
the HgBr2 case, a very molecular liquid like water, a clear Grotthuss chain of
bromide transfers was observed in simulation when seeding the system with a
HgBr(+) cation and HgBr3 (-) anion. The first conclusion is that the hopping
mechanism offered for molten BiCl3 is simply the Grotthuss mechanism for
conduction, applicable not just to H(+) ions, but also to halide ions in post
transition-metal halide melts. Second, it is conjectured that the conductivity
maximum is due to rising activation energy in network-covalent (halide-bridging)
melts (BiCl3, SnCl2, PbCl2), but possibly a falling Arrhenius prefactor
(collision frequency) for molecular melts (HgBr2).
PMID- 27609002
TI - Equilibrium crystal phases of triblock Janus colloids.
AB - Triblock Janus colloids, which are colloidal spheres decorated with attractive
patches at each pole, have recently generated significant interest as potential
building blocks for functional materials. Their inherent anisotropy is known to
induce self-assembly into open structures at moderate temperatures and pressures,
where they are stabilized over close-packed crystals by entropic effects. We
present a numerical investigation of the equilibrium phases of triblock Janus
particles with many different patch geometries in three dimensions, using Monte
Carlo simulations combined with free energy calculations. In all cases, we find
that the free energy difference between crystal polymorphs is less than 0.2 kBT
per particle. By varying the patch fraction and interaction range, we show that
large patches stabilize the formation of structures with four bonds per patch
over those with three. This transition occurs abruptly above a patch fraction of
0.30 and has a strong dependence on the interaction range. Furthermore, we find
that a short interaction range favors four bonds per patch, with longer range
increasingly stabilizing structures with only three bonds per patch. By
quantifying the effect of patch geometry on the stability of the equilibrium
crystal structures, we provide insights into the fundamental design rules for
constructing complex colloidal crystals.
PMID- 27609003
TI - Lattice energies of molecular solids from the random phase approximation with
singles corrections.
AB - We use the random phase approximation (RPA) method with the singles correlation
energy contributions to calculate lattice energies of ten molecular solids. While
RPA gives too weak binding, underestimating the reference data by 13.7% on
average, much improved results are obtained when the singles are included at the
GW singles excitations (GWSE) level, with average absolute difference to the
reference data of only 3.7%. Consistently with previous results, we find a very
good agreement with the reference data for hydrogen bonded systems, while the
binding is too weak for systems where dispersion forces dominate. In fact, the
overall accuracy of the RPA+GWSE method is similar to an estimated accuracy of
the reference data.
PMID- 27609004
TI - Adsorption of ethylene on Sn and In terminated Si(001) surface studied by
photoelectron spectroscopy and scanning tunneling microscopy.
AB - Interaction of ethylene (C2H4) with Si(001)-Sn-2 * 2 and Si(001)-In-2 * 2 at room
temperature has been studied using core level (C 1s) X-ray photoelectron
spectroscopy with synchrotron radiation and scanning tunneling microscopy. Sn and
In form similar dimer chains on Si(001)2 * 1, but exhibit different interaction
with ethylene. While ethylene adsorbs on top of Sn dimers of the Si(001)-Sn-2 * 2
surface, the Si(001)-In-2 * 2 surface turned out to be inert. Furthermore, the
reactivity of the Sn terminated surface is found to be considerably decreased in
comparison with Si(001)2 * 1. According to the proposed adsorption model ethylene
bonds to Sn dimers via [2 + 2] cycloaddition by interacting with their pi dimer
bonds. In contrast, indium dimers do not contain pi bonds, which renders the In
terminated Si(001) surface inert for ethylene adsorption.
PMID- 27609005
TI - Adsorption, desorption, and film formation of quinacridone and its thermal
cracking product indigo on clean and carbon-covered silicon dioxide surfaces.
AB - The evaporation of quinacridone from a stainless steel Knudsen cell leads to the
partial decomposition of this molecule in the cell, due to its comparably high
sublimation temperature. At least one additional type of molecules, namely
indigo, could be detected in the effusion flux. Thermal desorption spectroscopy
and atomic force microscopy have been used to study the co-deposition of these
molecules on sputter-cleaned and carbon-covered silicon dioxide surfaces.
Desorption of indigo appears at temperatures of about 400 K, while quinacridone
desorbs at around 510 K. For quinacridone, a desorption energy of 2.1 eV and a
frequency factor for desorption of 1 * 10(19) s(-1) were calculated, which in
this magnitude is typical for large organic molecules. A fraction of the adsorbed
quinacridone molecules (~5%) decomposes during heating, nearly independent of the
adsorbed amount, resulting in a surface composed of small carbon islands. The
sticking coefficients of indigo and quinacridone were found to be close to unity
on a carbon covered SiO2 surface but significantly smaller on a sputter-cleaned
substrate. The reason for the latter can be attributed to insufficient energy
dissipation for unfavorably oriented impinging molecules. However, due to
adsorption via a hot-precursor state, the sticking probability is increased on
the surface covered with carbon islands, which act as accommodation centers.
PMID- 27609006
TI - From single molecules to water networks: Dynamics of water adsorption on Pt(111).
AB - The adsorption dynamics of water on Pt(111) was studied using ab initio molecular
dynamics simulations based on density functional theory calculations including
dispersion corrections. Sticking probabilities were derived as a function of
initial kinetic energy and water coverage. In addition, the energy distribution
upon adsorption was monitored in order to analyze the energy dissipation process.
We find that on the water pre-covered surface the sticking probability is
enhanced because of the attractive water-water interaction and the additional
effective energy dissipation channels to the adsorbed water molecules. The water
structures forming directly after the adsorption on the pre-covered surfaces do
not necessarily correspond to energy minimum structures.
PMID- 27609007
TI - Charge neutrality breakdown in confined aqueous electrolytes: Theory and
simulation.
AB - We study, using Density Functional theory (DFT) and Monte Carlo simulations,
aqueous electrolyte solutions between charged infinite planar surfaces, in
contact with a bulk salt reservoir. In agreement with recent experimental
observations [Z. Luo et al., Nat. Commun. 6, 6358 (2015)], we find that the
confined electrolyte lacks local charge neutrality. We show that a DFT based on a
bulk-HNC expansion properly accounts for strong electrostatic correlations and
allows us to accurately calculate the ionic density profiles between the charged
surfaces, even for electrolytes containing trivalent counterions. The DFT allows
us to explore the degree of local charge neutrality violation, as a function of
plate separation and bulk electrolyte concentration, and to accurately calculate
the interaction force between the charged surfaces.
PMID- 27609008
TI - Efficient dynamical correction of the transition state theory rate estimate for a
flat energy barrier.
AB - The recrossing correction to the transition state theory estimate of a thermal
rate can be difficult to calculate when the energy barrier is flat. This problem
arises, for example, in polymer escape if the polymer is long enough to stretch
between the initial and final state energy wells while the polymer beads undergo
diffusive motion back and forth over the barrier. We present an efficient method
for evaluating the correction factor by constructing a sequence of hyperplanes
starting at the transition state and calculating the probability that the system
advances from one hyperplane to another towards the product. This is analogous to
what is done in forward flux sampling except that there the hyperplane sequence
starts at the initial state. The method is applied to the escape of polymers with
up to 64 beads from a potential well. For high temperature, the results are
compared with direct Langevin dynamics simulations as well as forward flux
sampling and excellent agreement between the three rate estimates is found. The
use of a sequence of hyperplanes in the evaluation of the recrossing correction
speeds up the calculation by an order of magnitude as compared with the
traditional approach. As the temperature is lowered, the direct Langevin dynamics
simulations as well as the forward flux simulations become computationally too
demanding, while the harmonic transition state theory estimate corrected for
recrossings can be calculated without significant increase in the computational
effort.
PMID- 27609009
TI - Crazing of nanocomposites with polymer-tethered nanoparticles.
AB - The crazing behavior of polymer nanocomposites formed by blending polymer grafted
nanoparticles with an entangled polymer melt is studied by molecular dynamics
simulations. We focus on the three key differences in the crazing behavior of a
composite relative to the pure homopolymer matrix, namely, a lower yield stress,
a smaller extension ratio, and a grafted chain length dependent failure stress.
The yield behavior is found to be mostly controlled by the local nanoparticle
grafted polymer interfacial energy, with the grafted polymer-polymer matrix
interfacial structure being of little to no relevance. Increasing the attraction
between nanoparticle core and the grafted polymer inhibits void nucleation and
leads to a higher yield stress. In the craze growth regime, the presence of
"grafted chain" sections of ~100 monomers alters the mechanical response of
composite samples, giving rise to smaller extension ratios and higher drawing
stresses than for the homopolymer matrix. The dominant failure mechanism of
composite samples depends strongly on the length of the grafted chains, with
disentanglement being the dominant mechanism for short chains, while bond
breaking is the failure mode for chain lengths >10Ne, where Ne is the
entanglement length.
PMID- 27609010
TI - Publisher's Note: "Influence of water on supra-molecular assembly of 4,4'
dihydroxy azobenzene on Ag(111)" [J. Chem. Phys. 142, 101920 (2015)].
PMID- 27609011
TI - Normality that is abnormal.
AB - Supernormal conduction is defined as better-than-expected conduction in patients
with depressed conduction during a short interval in the ventricular cycle. It is
mainly observed in long-duration electrocardiogram (ECG) assessments. Its
occurrence during 12-lead ECG is uncommon and its interpretation demands
knowledge on electrophysiological alterations that are hard to understand. By
reporting this case we aim to propose a rationale sequence that should be
considered when facing an ECG with these same features, which would enable a
greater accuracy to make a definitive diagnosis.
PMID- 27609012
TI - Computing the spatial QRS-T angle using reduced electrocardiographic lead sets.
AB - The 'spatial QRS-T angle' (SA) is frequently determined using linear lead
transformation matrices that require the entire 12-lead electrocardiogram (ECG).
While this approach is adequate when using 12-lead ECG data that is recorded in
the resting supine position, it is not optimal in monitoring applications. This
is because maintaining a good quality recording of the complete 12-lead ECG in
monitoring applications is difficult. In this research, we assessed the
differences between the 'gold standard' SA as determined using the Frank VGG and
the SA as determined using different reduced lead systems (RLSs). The random
error component (span of the Bland-Altman 95% limits of agreement) of the
differences between the 'gold standard' SA and the SA values based upon the
different RLSs was quantified. This was performed for all 62 RLSs that can be
constructed from Mason-Likar (ML) limb leads I, II and all possible precordial
lead subsets that contain between one and five of the precordial leads V1 to V6.
The RLS with the smallest lead set size that produced SA estimates of a quality
similar to what is achieved using the ML 12-lead ECG was based upon ML limb leads
I, II and precordial leads V1, V3 and V6. The random error component (mean [95%
confidence interval]) associated with this RLS and the ML 12-lead ECG were found
to be 40.74 degrees [35.56 degrees -49.29 degrees ] and 39.57 degrees [33.78
degrees -45.70 degrees ], respectively. Our findings suggest that a RLS that is
based upon the ML limb leads I and II and the three best precordial leads can
yield SA estimates of a quality similar to what is achieved when using the
complete ML 12-lead ECG.
PMID- 27609013
TI - Efficacy of scaling and root planing with and without adjunct antimicrobial
photodynamic therapy on the expression of cytokines in the gingival crevicular
fluid of patients with periodontitis: A systematic review.
AB - BACKGROUND: The aim of the present review was to study the efficacy of scaling
and root planing (SRP) with and without adjunct antibacterial photodynamic
therapy (aPDT) on the expression of cytokines in the gingival crevicular fluid
(GCF) of patients with periodontitis. METHODS: In order to address the focused
question: "What is the efficacy of SRP with and without aPDT on the expression of
cytokines in the GCF of patients with periodontitis" an electronic search without
time or language restrictions was conducted up to and including July 2016 in
indexed databases using various key words. The exclusion criteria included
reviews, laboratory and experimental studies, case reports, commentaries, letters
to the editor, interviews, updates, studies where intervention group received
aPDT without previous SRP, and studies where local delivery of antibiotics was
used as adjunctive therapy to aPDT. RESULTS: Six randomized control trials were
included in the present systematic review. All studies included a control group
which received only SRP. Results from 34% of studies reported lower cytokine
levels among individuals receiving adjunct aPDT to SPT compared to patients
receiving SRP alone. Selective cytokines reduction in the GCF following SRP with
adjunct aPDT compared with SRP alone was reported in 50% of the studies. In one
study SRP with adjunct aPDT failed to reduce GCF cytokine concentration.
CONCLUSION: From the literature reviewed the efficacy aPDT as adjunct to SRP in
downregulating GCF cytokines remains debatable. Further well-designed studies are
needed in this regard.
PMID- 27609014
TI - Investigation of lipid peroxidation and antiapoptotic effects of zinc aganist
liver damage in diabetic rats.
AB - Several mechanisms for the pathogenesis of diabetic complications have been
proposed, one of which is abnormal zinc (Zn) homeostasis. Zn is necessary for
proper liver function since it has important antioxidant, anti-inflammatory, and
antiapoptotic properties. We aimed to investigate whether or not Zn has
morphologically protective effect on diabetes-induced liver damage in rats. In
addition, we have investigated the role of Zn supplementation on apoptosis, lipid
peroxidation levels, and the distribution of metallothionein (MT) in diabetic
liver tissue. Wistar albino rats were divided into four groups: control, Zn,
diabetic, and Zn-diabetic group. Experimental diabetes was induced by a single
dose streptozotocin intraperitoneally and Zn was administrated via gastric gavage
tube for 6 weeks. MT expressions were showed with immunohistochemical staining
and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay
was used for apoptosis. Also, Zn, MT, and malondialdehyde (MDA) levels were
determined in liver of rats. MDA levels of the Zn-supplemented diabetic group was
less than the diabetic group though MT levels were increased. The number of
apoptotic cells per unit area was found to be significantly decreased in this
group. In the Zn-supplemented diabetic group, fibrotic tissue density and the
collagen tissue density were observed less than the diabetic group. MT
immunoreactivity was observed less in Zn-supplemented diabetic group. In
conculusion, the present study indicated that Zn has a potential in preventing or
even repairing effect against diabetic damage of the liver cells by increasing
expression of MT and by reducing the apoptotic cell death and the oxidative
stress.
PMID- 27609015
TI - The altered liver microRNA profile in hepatotoxicity induced by rhizome Dioscorea
bulbifera in mice.
AB - MicroRNA (miRNA) has been reported to play important roles in regulating drug
induced liver injury. Ethyl acetate extract isolated from rhizoma Dioscoreae
bulbifera (EF) has been reported to induce hepatotoxicity in our previous
studies. This study aims to observe the altered liver miRNA profile and its
related signalling pathway involved in EF-induced hepatotoxicity. Serum
alanine/aspartate aminotransferase assay showed that EF (450 mg/kg)-induced
hepatotoxicity in mice. Results of miRNA chip analysis showed that the expression
of eight miRNAs was up-regulated and of other nine miRNAs was down-regulated in
livers from EF-treated mice. Further, the altered expression of miR-200a-3p, miR
5132-5p and miR-5130 was validated using real-time polymerase chain reaction
(PCR) assay. There were total seven predicted target genes of miR-200a-3p, miR
5132-5p and miR-5130. Only one kyoto encyclopedia genes and genomes pathway was
annotated using those target genes, which is protein processing in endoplasmic
reticulum (ER). Furthermore, liver expression of DnaJ subfamily A member 1, a key
gene involved in protein processing in ER based on the altered miRNAs, was
increased in EF-treated mice. In conclusion, the results demonstrated that EF
altered the expression of liver miRNA profile and its related signalling pathway,
which may be involved in EF-induced hepatotoxicity.
PMID- 27609016
TI - Gastric cancer: somatic genetics as a guide to therapy.
AB - Gastric cancer is the leading cause of cancer-related mortality across the world,
with poor prognosis and a median overall survival of <=12 months for advanced
stage gastric cancer. Environmental, genetic and other predisposing factors
contribute to the development of gastric cancer and a predominant factor was
found to be infection of Helicobacter pylori Advances in understanding the
deranged signalling pathways that are critical for normal cellular homeostasis
helped in the development of novel drugs that target specific proteins and
pathways to curtail the growth of gastric cancer. Genetic studies revealed
several single nucleotide polymorphisms, chromosomal aberrations and epigenetic
alterations that likely play a major role in elevating the susceptibility to
develop gastric cancer. Methylation pattern of specific genes may likely prove to
be a valid biomarker for early detection of gastric cancer, but much progress is
needed to establish specific markers. Important developments have been made in
targeting human epidermal growth factor receptor-2 and vascular endothelial
growth factor receptor 2 for treating advanced gastro-oesophageal junction
cancer, using specific monoclonal antibodies. Lack of efficacy with regard to
targeting other signalling pathways including mesenchymal-epithelial
transition/hepatocyte growth factor and mammalian target of rapamycin is probably
due to suboptimal patient selection for these clinical trials, which is probably
due to the lack of appropriate biomarkers, to decide on responsive patient
population. Besides the development of antagonists for the cell growth-related
signalling pathways, advances are also being made to tackle gastric cancer by
immunotherapies, targeting immune check-points, which may hold promise for better
treatment options in future.
PMID- 27609017
TI - New insights into the genetic component of non-infectious uveitis through an
Immunochip strategy.
AB - BACKGROUND: Large-scale genetic studies have reported several loci associated
with specific disorders involving uveitis. Our aim was to identify genetic risk
factors that might predispose to uveitis per se, independent of the clinical
diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613
cases and 3693 unaffected controls from three European case/control sets were
genotyped using the Immunochip array. Only patients with non-infectious non
anterior uveitis and without systemic features were selected. To perform a more
comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs,
classical alleles and polymorphic amino acid variants were obtained via
imputation. A meta-analysis combining the three case/control sets was conducted
by the inverse variance method. RESULTS: The highest peak belonged to the HLA
region. A more detailed analysis of this signal evidenced a strong association
between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E
35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid
positions for this disease. In patients with intermediate and posterior uveitis,
the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA
(p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10,
OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside
the HLA region, the MAP4K4/IL1R2 locus reached statistical significance
(rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five
other loci. CONCLUSIONS: We have further interrogated the association between the
HLA region and non-infectious non-anterior uveitis. In addition, we have
identified a new non-HLA susceptibility factor and proposed additional risk loci
with putative roles in this complex condition.
PMID- 27609019
TI - Outcome of nutritional screening in the acute paediatric setting.
AB - INTRODUCTION: Multiple nutritional risk assessment tools are available, but there
are limited data on their application in the acute setting. We explored the
validity of two tools in a tertiary Children's Hospital's acute unit and the
cohort's nutritional status using WHO definitions. METHODS: Prospective study
n=300 (median 38 months; 44.6% female; 25.7% <=12 months). Participants had
standard anthropometry measured, all were screened using the Screening Tool for
the Assessment of Malnutrition in Paediatrics (STAMP), the Paediatric
Malnutrition Screening Tool (PMST) (modified STAMP) and 125 were additionally
screened using the Paediatric Yorkhill Malnutrition Screening (PYMS) tool.
RESULTS: The percentages with medium/high nutritional risk were as follows: STAMP
73.1%, PMST 79.3% and PYMS 30%. Height/weight were normally distributed with:
3.4% stunted (height-for-age z-score <-2); aged <= 5 years, 6.8% wasted (weight
for-height z-score (WHZ) <-2), 17.9% overweight (WHZ 1-2) and 6.2% obese (WHZ
>2); aged >5 years, 5.8% thin (body mass index (BMI)-z-score (BAZ) <-2), 17.3%
overweight (BAZ 1-2) and 5.8% obese (BAZ >2). The tools showed poor specificity
and variable sensitivities when compared with WHO malnutrition criteria, with
positive predictive values of <50%. kappa-Analysis also showed poor agreement
between the tools and the WHO cut-offs. CONCLUSION: These results suggest that
nutritional screening tools have poor sensitivity and are difficult to interpret
in the acute setting. It may be more effective to include the assessment of
weight and height and nutritional intake in the context of the acute presentation
as part of routine clinical assessment rather than relying on screening tools to
identify those at risk.
PMID- 27609020
TI - Pneumatosis intestinalis.
PMID- 27609018
TI - Comparison of pharmacological and non-pharmacological interventions to prevent
delirium in critically ill patients: a protocol for a systematic review
incorporating network meta-analyses.
AB - BACKGROUND: Delirium is characterized by acute changes in mental status including
inattention, disorganized thinking, and altered level of consciousness, and is
highly prevalent in critically ill adults. Delirium has adverse consequences for
both patients and the healthcare system; however, at this time, no effective
treatment exists. The identification of effective prevention strategies is
therefore a clinical and research imperative. An important limitation of previous
reviews of delirium prevention is that interventions were considered in isolation
and only direct evidence was used. Our systematic review will synthesize all
existing data using network meta-analysis, a powerful statistical approach that
enables synthesis of both direct and indirect evidence. METHODS: We will search
Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March
2016. We will search the PROSPERO registry for protocols and the Cochrane Library
for published systematic reviews. We will examine reference lists of pertinent
reviews and search gr ey literature and the International Clinical Trials
Registry Platform for unpublished studies and ongoing trials. We will include
randomized and quasi-randomized trials of critically ill adults evaluating any
pharmacological, non-pharmacological, or multi-component intervention for
delirium prevention, administered in or prior to (i.e., peri-operatively)
transfer to the ICU. Two authors will independently screen search results and
extract data from eligible studies. Risk of bias assessments will be completed on
all included studies. To inform our network meta-analysis, we will first conduct
conventional pair-wise meta-analyses for primary and secondary outcomes using
random-effects models. We will generate our network meta-analysis using a
Bayesian framework, assuming a common heterogeneity parameter across all
comparisons, and accounting for correlations in multi-arm studies. We will
perform analyses using WinBUGS software. DISCUSSION: This systematic review will
address the existing knowledge gap regarding best practices for delirium
prevention in critically ill adults by synthesizing evidence from trials of
pharmacological, non-pharmacological, and multi-component interventions
administered in or prior to transfer to the ICU. Use of network meta-analysis
will clarify which delirium prevention strategies are most effective in improving
clinical outcomes while causing least harm. The network meta-analysis is a novel
approach and will provide knowledge users and decision makers with comparisons of
multiple interventions of delirium prevention strategies. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42016036313.
PMID- 27609022
TI - Erratum to: Socioeconomic status as a moderator between frailty and mortality at
old ages.
PMID- 27609021
TI - Biochemical and transcriptomic analyses reveal different metabolite biosynthesis
profiles among three color and developmental stages in 'Anji Baicha' (Camellia
sinensis).
AB - BACKGROUND: The new shoots of the albino tea cultivar 'Anji Baicha' are yellow or
white at low temperatures and turn green as the environmental temperatures
increase during the early spring. 'Anji Baicha' metabolite profiles exhibit
considerable variability over three color and developmental stages, especially
regarding the carotenoid, chlorophyll, and theanine concentrations. Previous
studies focused on physiological characteristics, gene expression differences,
and variations in metabolite abundances in albino tea plant leaves at specific
growth stages. However, the molecular mechanisms regulating metabolite
biosynthesis in various color and developmental stages in albino tea leaves have
not been fully characterized. RESULTS: We used RNA-sequencing to analyze 'Anji
Baicha' leaves at the yellow-green, albescent, and re-greening stages. The leaf
transcriptomes differed considerably among the three stages. Functional
classifications based on Gene Ontology enrichment and Kyoto Encyclopedia of Genes
and Genomes enrichment analyses revealed that differentially expressed unigenes
were mainly related to metabolic pathways, biosynthesis of secondary metabolites,
phenylpropanoid biosynthesis, and carbon fixation in photosynthetic organisms.
Chemical analyses revealed higher beta-carotene and theanine levels, but lower
chlorophyll a levels, in the albescent stage than in the green stage.
Furthermore, unigenes involved in carotenoid, chlorophyll, and theanine
biosyntheses were identified, and the expression patterns of the differentially
expressed unigenes in these biosynthesis pathways were characterized. Through co
expression analyses, we identified the key genes in these pathways. These genes
may be responsible for the metabolite biosynthesis differences among the
different leaf color and developmental stages of 'Anji Baicha' tea plants.
CONCLUSIONS: Our study presents the results of transcriptomic and biochemical
analyses of 'Anji Baicha' tea plants at various stages. The distinct
transcriptome profiles for each color and developmental stage enabled us to
identify changes to biosynthesis pathways and revealed the contributions of such
variations to the albino phenotype of tea plants. Furthermore, comparisons of the
transcriptomes and related metabolites helped clarify the molecular regulatory
mechanisms underlying the secondary metabolic pathways in different stages.
PMID- 27609024
TI - Effects of in vitro digestion and storage on the phenolic content and antioxidant
capacity of a red grape pomace.
AB - Red grape pomace (RGP) is a major winery by-product with interesting applications
due to its high phenolic content and antioxidant capacity. Effects of in vitro
gastrointestinal digestion and storage on the phenolic content and antioxidant
capacity of RGP were studied. RGP polyphenols were stable under stomach-mimicking
conditions and more sensitive to small intestine conditions, reducing
anthocyanins and flavonols. After 3- and 6-month storage, at either 4 or 25
degrees C, there were no changes in the total phenolic and condensed tannin
content, or antioxidant capacity (evaluated by ABTS, FRAP, ORAC assays); however,
after 9 months these parameters decreased. Contrarily, chromatic b* values were
higher, thus the samples had more intense red color, which may be related to the
increased condensed tannin content. Storage time or temperature induced no
changes in microbiological load. RGP preserves high antioxidant capacity after
storage and in vitro digestion and thus presents potential as a functional
ingredient or nutraceutical.
PMID- 27609025
TI - [Ranibizumab and exudative age-related macular degeneration: 5-year multicentric
functional and anatomical results in real-life practice].
AB - PURPOSE: The goal of this study was to evaluate five year functional and
anatomical outcomes of wet AMD patients treated with ranibizumab according to a
pro re nata (PRN) regimen in real-life practice. METHODS: A retrospective,
multicentric chart review of 201 eyes of 201 patients who underwent their first
ranibizumab intravitreal injection (IVT) between January 1, 2007 and December 31,
2008 was performed. Best-corrected visual acuity (BCVA), central macular
thickness (CMT) on SD-OCT, number of IVT and follow-up visits were collected at
baseline and during the entire follow-up period of 5 years. RESULTS: Mean BCVA at
baseline was 52.3+/-16.5 letters. Mean BCVA change from baseline was respectively
+2.8, +2.5, +1.8, -0.6 at 1, 2, 3, 4 years of follow-up. At year 5, 43% of eyes
had a stable or improved letter score (>=0 letter gain), whereas 29% declined by
15 letters or more, with an overall significant mean decline of 2.8 letters
(P<0.05). No correlation was observed between final visual outcome and age,
baseline BCVA, type of neovascularization, naive status, number of IVT or number
of follow-up visits. On SD-OCT, mean CMT was 293+/-96MUm at baseline and was
significantly reduced compared to baseline at each year end-point (P<0.005). The
mean number of IVT was 15+/-10.4 at year 5, with 55% of eyes still being under
active treatment. CONCLUSION: PRN ranibizumab in real-life practice improved or
stabilized visual acuity over 4 years. During the 5th year, progressive decline
of visual acuity was observed.
PMID- 27609023
TI - A 19-Gene expression signature as a predictor of survival in colorectal cancer.
AB - BACKGROUND: Histopathological assessment has a low potential to predict clinical
outcome in patients with the same stage of colorectal cancer. More specific and
sensitive biomarkers to determine patients' survival are needed. We aimed to
determine gene expression signatures as reliable prognostic marker that could
predict survival of colorectal cancer patients with Dukes' B and C. METHODS: We
examined microarray gene expression profiles of 78 archived tissues of patients
with Dukes' B and C using the Illumina DASL assay. The gene expression data were
analyzed using the GeneSpring software and R programming. RESULTS: The outliers
were detected and replaced with randomly chosen genes from the 90 % confidence
interval of the robust mean for each group. We performed three statistical
methods (SAM, LIMMA and t-test) to identify significant genes. There were 19
significant common genes identified from microarray data that have been
permutated 100 times namely NOTCH2, ITPRIP, FRMD6, GFRA4, OSBPL9, CPXCR1, SORCS2,
PDC, C12orf66, SLC38A9, OR10H5, TRIP13, MRPL52, DUSP21, BRCA1, ELTD1, SPG7, LASS6
and DUOX2. This 19-gene signature was able to significantly predict the survival
of patients with colorectal cancer compared to the conventional Dukes'
classification in both training and test sets (p < 0.05). The performance of this
signature was further validated as a significant independent predictor of
survival using patient cohorts from Australia (n = 185), USA (n = 114), Denmark
(n = 37) and Norway (n = 95) (p < 0.05). Validation using quantitative PCR
confirmed similar expression pattern for the six selected genes. CONCLUSION:
Profiling of these 19 genes may provide a more accurate method to predict
survival of patients with colorectal cancer and assist in identifying patients
who require more intensive treatment.
PMID- 27609026
TI - Methotrexate is not associated with increased liver cirrhosis in a population
based cohort of rheumatoid arthritis patients with chronic hepatitis C.
AB - A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis
and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although
the risk is low compared to psoriatics. We therefore conducted a population-based
cohort study to investigate the impact of long-term MTX use on the risk of
chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data
from the National Health Insurance Research Database in Taiwan and identified 450
incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users)
from January 1, 1998 to December 31, 2007. After a median follow-up of more than
5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver
cirrhosis. We did not find an increased risk of liver cirrhosis among CHC
patients with long-term MTX use for RA. Furthermore, there was no occurrence of
liver cirrhosis among the 43 MTX users with a cumulative dose ?3 grams after 108
months of treatment. In conclusion, our data showed that long-term MTX use is not
associated with an increased risk for liver cirrhosis among RA patients with CHC.
However, these results should be interpreted with caution due to potential bias
in the cohort.
PMID- 27609027
TI - Descriptive figures for differences in parenting and infant night-time distress
in the first three months of age.
AB - : Aim To provide descriptive figures for infant distress and associated parenting
at night in normal London home environments during the first three months of age.
BACKGROUND: Most western infants develop long night-time sleep periods by four
months of age. However, 30% of infants in many countries sleep for short periods
and cry out on waking in the night: the most common type of infant sleep
behaviour problem. Preventive interventions may help families and improve
services. There is evidence that 'limit-setting' parenting, which is common in
western cultures, supports the development of settled infant night-time
behaviour. However, a recent review has challenged this and argued that this form
of parenting risks distressing infants. This study describes limit-setting
parenting as practiced in London, compares it with 'infant-cued' parenting and
measures the associated infant distress. METHODS: Longitudinal infrared video,
diary and questionnaire observations comparing a General-Community (n=101) group
and subgroups with a Bed-Sharing (n=19) group on measures of infant and parenting
behaviours at night. Findings General-Community parents took longer to detect and
respond to infant waking and signalling, and to begin feeding, compared with the
highly infant-cued care provided by Bed-Sharing parents. The average latency in
General-Community parents' responding to infant night-time waking was 3.5 min,
during which infants fuss/cried for around 1 min. Compared with Bed-Sharing
parenting, General-Community parenting was associated with increased infant
distress of around 30 min/night at two weeks, reducing to 12 min/night by three
months of age. However, differences in infant distress between General-Community
subgroups adopting limit-setting versus infant-cued parenting were not large or
statistically significant at any age. The figures provide descriptive evidence
about limit-setting parenting which may counter some doubts about this form of
parenting and help parents and professionals to make choices.
PMID- 27609028
TI - Staphylococcus lugdunensis, a serious pathogen in periprosthetic joint
infections: comparison to Staphylococcus aureus and Staphylococcus epidermidis.
AB - OBJECTIVES: The aim of this study was to assess the characteristics of
periprosthetic joint infection (PJI) due to Staphylococcus lugdunensis and to
compare these to the characteristics of PJI due to Staphylococcus aureus and
Staphylococcus epidermidis. METHODS: A retrospective multicentre study including
all consecutive cases of S. lugdunensis PJI (2000-2014) was performed. Eighty
eight cases of staphylococcal PJI were recorded: 28 due to S. lugdunensis, 30 to
S. aureus, and 30 to S. epidermidis, as identified by Vitek 2 or API Staph
(bioMerieux). RESULTS: Clinical symptoms were more often reported in the S.
lugdunensis group, and the median delay between surgery and infection was shorter
for the S. lugdunensis group than for the S. aureus and S. epidermidis groups.
Regarding antibiotic susceptibility, the S. lugdunensis strains were susceptible
to antibiotics and 61% of the patients could be treated with levofloxacin +
rifampicin. The outcome of the PJI was favourable for 89% of patients with S.
lugdunensis, 83% with S. aureus, and 97% with S. epidermidis. CONCLUSION: S.
lugdunensis is an emerging pathogen with a pathogenicity quite similar to that of
S. aureus. This coagulase-negative Staphylococcus must be identified precisely in
PJI, in order to select the appropriate surgical treatment and antibiotics .
PMID- 27609029
TI - Complete mesh migration into the small bowel after incisional hernia repair: a
case report and literature review.
AB - INTRODUCTION: Mesh migration into the intestine is very rare after incisional
hernia repair. CASE REPORT: We report the case of transmural mesh migration from
the abdominal wall into the small bowel presenting as recurrent small bowel
obstruction 18 years after repeated surgical repair of an incisional ventral
hernia. At surgery, a mesh was found inside the resected ileal loop. DISCUSSION:
Mesh migration into the intestine is a possible, although very rare, complication
after incisional hernia repair with nonabsorbable meshes. It tends to occur late
with obstructive symptoms, especially if the small intestine is involved.
Avoiding the direct contact between the mesh and the intestinal wall may help to
reduce this complication.
PMID- 27609030
TI - HIV prevention advice for people with serious mental illness.
AB - BACKGROUND: People with serious mental illness have rates of Human Immuno
deficiency Virus (HIV) infection higher than expected in the general population
for the same demographic area. Despite this elevated prevalence, UK national
strategies around sexual health and HIV prevention do not state that people with
serious mental illness are a high risk group. However, a significant proportion
in this group are sexually active and engage in HIV-risk behaviours including
having multiple sexual partners, infrequent use of condoms and trading sex for
money or drugs. Therefore we propose the provision of HIV prevention advice could
enhance the physical and social well being of this population. OBJECTIVES: To
assess the effects of HIV prevention advice in reducing morbidity, mortality and
preserving the quality of life in people with serious mental illness. SEARCH
METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (24
January 2012; 4 July 2016). SELECTION CRITERIA: We planned to include all
randomised controlled trials focusing on HIV prevention advice versus standard
care or comparing HIV prevention advice with other more focused methods of
delivering care or information for people with serious mental illness. DATA
COLLECTION AND ANALYSIS: Review authors (NW, AC, AA, GT) independently screened
search results and did not identify any studies that fulfilled the review's
criteria. MAIN RESULTS: We did not identify any randomised studies that evaluated
advice regarding HIV for people with serious mental illness. The excluded studies
illustrate that randomisation of packages of care relevant to both people with
serious mental illness and HIV risk are possible. AUTHORS' CONCLUSIONS: Policy
makers, clinicians, researchers and service users need to collaborate to produce
guidance on how best to provide advice for people with serious mental illness in
preventing the spread of HIV infection. It is entirely feasible that this could
be within the context of a well-designed simple large randomised study.
PMID- 27609031
TI - MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of
non-alcoholic steatohepatitis.
AB - Non-alcoholic steatohepatitis (NASH), a metabolic disorder consisting of
steatosis and inflammation, is considered the hepatic equivalent of metabolic
syndrome and can result in irreversible liver damage. Macrophage-stimulating
protein (MSP) is a hepatokine that potentially has a beneficial role in hepatic
lipid and glucose metabolism via the activation of AMP-activated protein kinase
(AMPK). In the current study, we investigated the regulatory role of MSP in the
development of inflammation and lipid metabolism in various NASH models, both in
vitro and ex vivo. We observed that MSP treatment activated the AMPK signaling
pathway and inhibited lipopolysaccharide (LPS)- and palmitic acid (PA)-induced
gene expression of pro-inflammatory cytokines in primary mouse hepatocytes. In
addition, MSP treatment resulted in a significant reduction in PA-induced lipid
accumulation and inhibited the gene expression of key lipogenic enzymes in HepG2
cells. Upon short hairpin RNA-induced knockdown of RON (the membrane-bound
receptor for MSP), the anti-inflammatory and anti-lipogenic effects of MSP were
markedly ablated. Finally, to mimic NASH ex vivo, we challenged bone marrow
derived macrophages with oxidized low-density lipoprotein (oxLDL) in combination
with LPS. OxLDL+LPS exposure led to a marked inhibition of AMPK activity and a
robust increase in inflammation. MSP treatment significantly reversed these
effects by restoring AMPK activity and by suppressing pro-inflammatory cytokine
gene expression and secretion under this condition. Taken together, these data
suggest that MSP is an effective inhibitor of inflammation and lipid accumulation
in the stressed liver, thereby indicating that MSP has a key regulatory role in
NASH.
PMID- 27609032
TI - Genetic and tissue level muscle-bone interactions during unloading and
reambulation.
AB - Little is known about interactions between muscle and bone during the removal and
application of mechanical signals. Here, we applied 3wk of hindlimb unloading
followed by 3wk of reambulation to a genetically heterogeneous population of 352
adult mice and tested the hypothesis that changes in muscle are associated with
changes in bone at the level of the tissue and the genome. During unloading and
relative to normally ambulating control mice, most mice lost muscle and cortical
bone with large variability across the population. During reambulation,
individual mice regained bone and muscle at different rates. Across mice, changes
in muscle and trabecular/cortical bone were not correlated to each other during
unloading or reambulation. For unloading, we found one significant quantitative
trait locus (QTL) for muscle area and five QTLs for cortical bone without overlap
between mechano-sensitive muscle and cortical bone QTLs (but some overlap between
muscle and trabecular QTLs). The low correlations between morphological changes
in muscle and bone, together with the largely distinct genetic regulation of the
response indicate that the premise of a muscle-bone unit that co-adjusts its size
during (un)loading may need to be reassessed.
PMID- 27609034
TI - Effects of whole body vibration exercises on bone mineral density of women with
postmenopausal osteoporosis without medications: novel findings and literature
review.
AB - OBJECTIVES: The aim of this study was to review the literature about the effect
of whole body vibration exercise in the BMD in patients with postmenopausal
osteoporosis without medications. METHODS: A systematic review was performed.
RESULTS: The frequency of the mechanical vibration used in the protocols has
varied from 12 to 90 Hz. The time used in the protocols varied from 2 up to 22
months. Techniques with X-rays were used in nine of the twelve publications
analyzed, the Dual energy X-ray absorptiometry (DEXA) in eight studies and the
High resolution peripheral quantitative computed tomography (HR-pQCT) in one
publication. The concentration of some biomarkers was determined, as the
sclerostin, the bone alkaline phosphatase, N-telopeptide X and 25-hydroxyvitamin
D. Among the twelve articles analyzed, seven of them have shown an improvement of
the BMD of some bone of postmenopausal women exposed to whole body vibration
exercises not associated to medications; as well as modifications in biomarkers.
PMID- 27609033
TI - Early vibration assisted physiotherapy in toddlers with cerebral palsy - a
randomized controlled pilot trial.
AB - OBJECTIVES: to investigate feasibility, safety and efficacy of home-based side
alternating whole body vibration (sWBV) to improve motor function in toddlers
with cerebral palsy (CP). METHODS: Randomized controlled trial including 24
toddlers with CP (mean age 19 months (SD+/-3.1); 13 boys). INTERVENTION: 14 weeks
sWBV with ten 9-minute sessions weekly (non-individualized). Group A started with
sWBV, followed by 14 weeks without; in group B this order was reversed.
Feasibility (>=70% adherence) and adverse events were recorded; efficacy
evaluated with the Gross Motor Function Measure (GMFM-66), Pediatric Evaluation
of Disability Inventory (PEDI), at baseline (T0), 14 (T1) and 28 weeks (T2).
RESULTS: Developmental change between T0 and T1 was similar in both groups;
change scores in group A and B: GMFM-66 2.4 (SD+/-2.1) and 3.3 (SD+/-2.9)
(p=0.412); PEDI mobility 8.4 (SD+/-6.6) and 3.5 (SD+/-9.2) (p=0.148),
respectively. In two children muscle tone increased post-sWBV. 24 children
received between 67 and 140 sWBV sessions, rate of completed sessions ranged from
48 to 100% and no dropouts were observed. CONCLUSION: A 14-week home-based sWBV
intervention was feasible and safe in toddlers with CP, but was not associated
with improvement in gross motor function.
PMID- 27609035
TI - Effects of whole-body vibration applied to lower extremity muscles during decline
bench press exercise.
AB - OBJECTIVES: To evaluate the effects of whole-body vibration (WBV) on skeletal
muscle activity and power performance of the upper body during decline bench
press exercise at different loads. METHODS: Forty-seven healthy young and active
male students volunteered. Each performed dynamic decline bench press repetitions
with and without WBV (50 Hz, 2.2 mm) applied through a hamstring bridge exercise
at three different loads of their 1-repetition maximum (1RM): 30%, 50%, and 70%
1RM. Muscle activity of the triceps brachii (TB), biceps brachii (BB), pectoralis
major (PM), and biceps femoris (BF) was measured with surface electromyography
electrodes and kinetic parameters of the repetitions were measured with a rotary
encoder. RESULTS: WBV increased peak power (PP) output during the 70% 1RM
condition (p<0.01). Muscle activity was increased with WBV in the TB and BF
muscles at all loads (p<0.05). There were no effects of WBV on BB or PM muscles.
CONCLUSION: WBV applied through a hamstring bridge exercise increases TB muscle
activity during a decline bench press and this augmentation contributes to an
increased peak power at higher loads and increased peak acceleration at lower
loads.
PMID- 27609036
TI - In vivo dynamic compression has less detrimental effect than static compression
on newly formed bone of a rat caudal vertebra.
AB - Fusionless devices are currently designed to treat spinal deformities such as
scoliosis by the application of a controlled mechanical loading. Growth
modulation by dynamic compression was shown to preserve soft tissues. The
objective of this in vivo study was to characterize the effect of static vs.
dynamic loading on the bone formed during growth modulation. Controlled
compression was applied during 15 days on the 7(th) caudal vertebra (Cd7) of rats
during growth spurt. The load was sustained in the "static" group and
sinusoidally oscillating in the "dynamic" group. The effect of surgery and of the
device was investigated using control and sham (operated on but no load applied)
groups. A high resolution CT-scan of Cd7 was acquired at days 2, 8 and 15 of
compression. Growth rates, histomorphometric parameters and mineral density of
the newly formed bone were quantified and compared. Static and dynamic loadings
significantly reduced the growth rate by 20% compared to the sham group. Dynamic
loading preserved newly formed bone histomorphometry and mineral density whereas
static loading induced thicker (+31%) and more mineralized (+12%) trabeculae. A
significant sham effect was observed. Growth modulation by dynamic compression
constitutes a promising way to develop new treatment for skeletal deformities.
PMID- 27609037
TI - The molecular basis of bone mechanotransduction.
AB - The skeleton has the ability to perfectly adapt to external forces of the
operating environment, by altering its morphology and metabolism in order to meet
different needs. This unique adaptive capacity of the skeleton creates an
interesting range of biological questions concerning the perception of mechanical
or other kinds of signals, the type of receptor, and the molecular pathways
involved in this adaptation. Studies of the characteristics of the cellular
engineering provide a host of new information that confers to osteocytes the role
of the protagonist in the perception and regulation of mechanical effects on the
skeleton. The identity of mechanoreceptors is manifold and concerns ion channels,
integrins, cell membrane, the cytoskeleton, and other systems. A similar
multiplicity characterizes the intracellular signaling. This review describes
recent data concerning the outward force reception systems and intracellular
transduction pathways of information transfer leading to the continuous
adaptation of bone tissue. Increased appreciation of the importance of the
mechanical environment in regulating and determining the effectiveness of
structural adjustment of the skeleton defines new horizons for the discovery of
novel therapeutic approaches to diseases associated with bone loss.
PMID- 27609038
TI - Longitudinal bone, muscle and adipose tissue changes in physically active
subjects - sex differences during adolescence and maturity.
AB - OBJECTIVES: To explore changes in bone, muscle and adipose tissue composition in
athletes with high physical activity levels at different stages of life. METHODS:
Thigh MRIs were acquired at baseline and 2-year follow-up for 20 young (16+/-1
years) and 20 mature (46+/-5 years) athletes (10 males, 10 females,
respectively). Longitudinal changes in cross-sectional areas (CSAs) of femoral
bone, quadriceps muscle, and thigh subcutaneous (SCF) and intermuscular (IMF)
adipose tissue were evaluated. RESULTS: Adolescent males displayed significant
muscle (+5.0%, 95%CI: 0.8, 9.2) and bone growth (+2.9%, 95%CI: 1.3, 4.5), whereas
adolescent females did not (muscle: +0.8%, 95%CI: -2.2, 3.8; bone: +1.9%, 95%CI:
2.1, 5.6). Adolescent and mature females showed significant SCF increases
(+11.0%, 95%CI: 0.9, 21.1 and +6.0%, 95%CI: 0.6, 11.4, respectively), whereas
adolescent and mature males did not (+7.2%, 95%CI: -8.0, 22.5 and +1.5%, 95%CI:
9.7, 11.8, respectively). Muscle and bone changes were highly correlated in
adolescent males (r=0.66), mature males (r=0.75) and mature females (r=0.68) but
not in adolescent females (r=-0.11). CONCLUSIONS: The results suggest sex
specific patterns of age-related change in bone, muscle and adipose tissue, and
tight coupling of bone and muscle growth. Sex-specific bone-muscle-adipose tissue
relationships may have implications for understanding sex differences in fracture
risk.
PMID- 27609040
TI - Functional in vitro tension measurements of fascial tissue - a novel modified
superfusion approach.
AB - INTRODUCTION: While two laboratory techniques are commonly used to assess the
tensile properties of muscle tissue, emerging evidence suggests that the fascial
components of these tissues also serve an active role in force generation. Hence,
we investigated whether these techniques are sensitive for assessment of fascial
micromechanics. METHODS: Force measurements on dissected fascial tissue were
performed either using the classical immersion organ bath or using an improved
superfusion approach simulating pulsed pharmacological triggers. Rat deep dorsal
fascial strips as well as rat testicular capsule were pharmacologically
challenged either with mepyramine or oxytocin. RESULTS: The classical immersion
technique yielded a lower force response to mepyramine than the superfusion
method (median: 367.4 vs. 555.4uN/mm(2)). Pause in irrigation before application
reduced irregularities during bolus application. The superfusion approach was
improved further by the following points: The high sensitivity of the superfusion
method to bolus addition was voided by deviation of fluid supply during bolus
addition. CONCLUSION: Although both methods demonstrated pharmacologically
induced contractile responses in lumbar fascia samples, the modified superfusion
method may improve force registrations of slow contracting fascial tissue and
minimize artefacts of fluid application.
PMID- 27609039
TI - Pediatric data for dual X-ray absorptiometric measures of normal lumbar bone
mineral density in children under 5 years of age using the lunar prodigy
densitometer.
AB - OBJECTIVES: Knowledge of physiological variations of bone mineral density (BMD)
in newborns and infants is necessary to evaluate pathological changes associated
with fractures. Limited reference data for children under 5 years old are
available. This study provides normative data of lumbar BMD for the Lunar Prodigy
in young children under 5 years old. SUBJECTS AND METHODS: We assessed cross
sectionally 155 healthy children (77 boys, 80% Caucasian), ranging in age from
newborn to the age of 5 years. Lumbar bone mineral content (BMC) and areal BMD
were measured by dual-energy X-ray absorptiometry using a Lunar Prodigy
absorptiometer. Volumetric BMD was calculated using the Kroeger and Carter
methods. RESULTS: BMC and areal BMD increased from birth to 5 years (p<0.001).
Volumetric BMD did not change with age. BMD and BMC correlated with age, weight
and height (R(2)>=0.85 for all), with a maximum gain between the ages of 1 and 4
years, which did not follow the same pattern as height velocity. We did not find
significant sex difference for any of the three measured parameters. CONCLUSION:
This study provides normative data for lumbar spine densitometry of infants and
young children using the Lunar Prodigy DXA system.
PMID- 27609041
TI - Needle tract seeding after core biopsy in a knee tumor; should biopsy tract be
excised?
PMID- 27609042
TI - Article retraction. Sato Y, Honda Y, Iwamoto J, Amano N. Comparison of non
vertebral fracture between minodronate and risedronate therapy in elderly female
patients with Alzheimer disease. J Musculoskelet Neuronal Interact 2013;13:346
52.
PMID- 27609044
TI - The role of electron confinement in Pd films for the oscillatory magnetic
anisotropy in an adjacent Co layer.
AB - We demonstrate the interplay between quantum well states in Pd and the magnetic
anisotropy in Pd/Co/Cu (0 0 1) by combined scanning tunneling spectroscopy (STS)
and magneto optical Kerr effect (MOKE) measurements. Low temperature scanning
tunneling spectroscopy reveals occupied and unoccupied quantum well states (QWS)
in atomically flat Pd films on Co/Cu (0 0 1). These states give rise to sharp
peaks in the differential conductance spectra. A quantitative analysis of the
spectra reveals the electronic dispersion of the Pd (0 0 1) d-band ([Formula: see
text]-type) along the [Formula: see text]-X direction. In situ MOKE experiments
on Pd/Co/Cu (1, 1, 13) uncover a periodic variation of the in-plane uniaxial
magnetic anisotropy as a function of Pd thickness with a period of 6 atomic
layers Pd. STS shows that QWS in Pd cross the Fermi level with the same
periodicity of 6 atomic layers. Backed by previous theoretical work we ascribe
the variation of the magnetic anisotropy in Co to QWS in the Pd overlayer. Our
results suggest a novel venue towards tailoring uniaxial magnetic anisotropy of
ferromagnetic films by exploiting QWS in an adjacent material with large spin
orbit coupling.
PMID- 27609043
TI - Written reply: "Optimal multibipolar radiofrequency parameters should overcome
heat-sink effect".
PMID- 27609045
TI - Understanding 2D atomic resolution imaging of the calcite surface in water by
frequency modulation atomic force microscopy.
AB - Frequency modulation atomic force microscopy (FM-AFM) experiments were performed
on the calcite (10[Formula: see text]4) surface in pure water, and a detailed
analysis was made of the 2D images at a variety of frequency setpoints. We
observed eight different contrast patterns that reproducibly appeared in
different experiments and with different measurement parameters. We then
performed systematic free energy calculations of the same system using atomistic
molecular dynamics to obtain an effective force field for the tip-surface
interaction. By using this force field in a virtual AFM simulation we found that
each experimental contrast could be reproduced in our simulations by changing the
setpoint, regardless of the experimental parameters. This approach offers a
generic method for understanding the wide variety of contrast patterns seen on
the calcite surface in water, and is generally applicable to AFM imaging in
liquids.
PMID- 27609047
TI - The Role of a Platelet Lysate-Based Compartmentalized System as a Carrier of
Cells and Platelet-Origin Cytokines for Periodontal Tissue Regeneration.
AB - Currently available clinical therapies are not capable to regenerate tissues that
are lost by periodontitis. Tissue engineering can be applied as a strategy to
regenerate reliably the tissues and function of damaged periodontium. A
prerequisite for this regeneration is the colonization of the defect with the
adequate cell populations. In this study, we proposed a bilayered system composed
of (1) a platelet lysate (PL)-based construct produced by crosslinking of PL
proteins with genipin (gPL) for the delivery of rat periodontal ligament cells
(rat-PDLCs); combined with (2) an injectable composite consisting of calcium
phosphate cement incorporated with PL-loaded poly(d, l-lactic-co-glycolic acid)
microspheres. This system was expected to promote periodontal regeneration by the
delivery of adequate progenitor cells and providing a stable system enriched with
adequate cytokines and growth factors for the orchestration of tissue regrowth in
periodontal defects. The bilayered system was tested in a three-wall intrabony
defect in rats and the healing of periodontal tissue was assessed 6 weeks after
surgery. Results showed that the bilayered system was able to promote the
regrowth of functional periodontal tissues, both with (cells + gPL) and without
the loading of PDLCs (gPL). Significant connective tissue attachment (45.0 +/-
15.0% and 64.0 +/- 15.0% for gPL and cells + gPL group, respectively) and new
bone area (33.8 +/- 21% and 21.3 +/- 3% for gPL and cells + gPL group,
respectively) were observed. Nevertheless, rat PDLCs delivered with gPL construct
in the defect area were hardly visible 6 weeks after surgery and did not
contribute for the regeneration of new periodontal tissue. Overall, our findings
show that the bilayered system promotes the stabilization of PL proteins on the
root surface and has a positive effect in the repair of periodontal tissues both
in quality and in quantity.
PMID- 27609048
TI - Meningioangiomatosis: A Disease With Many Radiological Faces.
PMID- 27609046
TI - miRNA-187-3p-Mediated Regulation of the KCNK10/TREK-2 Potassium Channel in a Rat
Epilepsy Model.
AB - Regulatory RNAs play a key role in the regulation of protein expression patterns
in neurological diseases. Here we studied the regulation of miRNAs in a chronic
rat model of temporal lobe epilepsy. The analysis was focused on a putative link
with pharmacoresponsiveness as well as the functional implications of the
regulation of a selected miRNA. The findings did not reveal a difference in
hippocampal miRNA expression between phenobarbital responders and nonresponders.
However, when comparing rats following status epilepticus with control rats we
identified 13 differentially expressed miRNAs with miRNA-187-3p being most
strongly regulated. mRNAs encoding KCNK10/TREK-2 as well as DYRK2 were confirmed
as targets of miRNA-187-3p. Expression of the potassium channel protein
KCNK10/TREK-2 negatively correlated with hippocampal miRNA-187-3p expression and
proved to be upregulated in the chronic phase of the epilepsy model. In
conclusion, our data do not suggest a relevant impact of miRNA expression
patterns on pharmacoresponsiveness. However, we confirmed regulation of miRNA-187
3p and demonstrated that it impacts the expression of the two-pore domain
potassium channel protein KCNK10/TREK-2. Considering evidence from brain ischemia
models, KCNK10/TREK-2 upregulation might serve a protective function with a
beneficial impact on astrocytic potassium and glutamate homeostasis.
PMID- 27609049
TI - IncN ST7 epidemic plasmid carrying blaIMP-4 in Enterobacteriaceae isolates with
epidemiological links to multiple geographical areas in China.
AB - OBJECTIVES: To characterize blaIMP-4-carrying plasmids originating from
inpatients in Hong Kong. METHODS: Sixteen blaIMP-4-carrying plasmids identified
among Enterobacteriaceae (nine Escherichia coli, four Klebsiella pneumoniae, two
Citrobacter freundii and one Enterobacter cloacae) recovered from 15 patients
were characterized. The isolates, collected during January 2010 to December 2013,
were retrospectively investigated by plasmid sequencing, molecular and fitness
studies. RESULTS: The blaIMP-4-carrying plasmids belonged to the IncN ST7 lineage
(~50 kb). Twelve of the 16 plasmids were epidemiologically linked to seven
different regions in China. Alignment of the complete plasmid sequences showed
identical plasmid backbones and two highly similar resistance regions, each
carrying one of two resistance genes (blaIMP-4 and qnrS1). The blaIMP-4 was
detected in a class 1 integron (containing blaIMP-4 and intron Kl.pn.13) that is
part of an IS6100-IS26 transposon-like structure. The nine E. coli carrying the
epidemic plasmid belonged to multiple multilocus STs (six ST542, one ST131, one
ST657 and one ST3177). Fitness assays performed on E. coli J53 recipients showed
that the presence of the epidemic plasmid did not have a significant biological
cost. CONCLUSIONS: This study identified a blaIMP-4-carrying IncN ST7 plasmid
disseminated among multiple enterobacterial species originating from patients
with epidemiological links to different regions in China.
PMID- 27609050
TI - Identification of inhibitors for single-stranded DNA-binding proteins in
eubacteria.
AB - OBJECTIVES: The increasing threat of drug-resistant bacteria establishes a
continuing need for the development of new strategies to fight infection. We
examine the inhibition of the essential single-stranded DNA-binding proteins
(SSBs) SSBA and SSBB as a potential antimicrobial therapy due to their importance
in DNA replication, activating the SOS response and promoting competence-based
mechanisms of resistance by incorporating new DNA. METHODS: Purified recombinant
SSBs from Gram-positive (Staphylococcus aureus and Bacillus anthracis) and Gram
negative (Escherichia coli and Francisella tularensis) bacteria were assessed in
a high-throughput screen for inhibition of duplex DNA unwinding by small molecule
inhibitors. Secondary electrophoretic mobility shift assays further validated the
top hits that were then tested for MICs using in vitro assays. RESULTS: We have
identified compounds that show cross-reactivity in vitro, as well as inhibition
of both F. tularensis and B. anthracis SSBA. Five compounds were moderately toxic
to at least two of the four bacterial strains in vivo, including two compounds
that were selectively non-toxic to human cells, 9-hydroxyphenylfluoron and
purpurogallin. Three of the SSBA inhibitors also inhibited S. aureus SSBB in Gram
positive bacteria. CONCLUSIONS: Results from our study support the potential for
SSB inhibitors as broad-spectrum antibacterial agents, with dual targeting
capabilities against Gram-positive bacteria.
PMID- 27609052
TI - Longitudinal (2001-14) analysis of enterococci and VRE causing invasive
infections in European and US hospitals, including a contemporary (2010-13)
analysis of oritavancin in vitro potency.
AB - OBJECTIVES: The objective of this study was to evaluate the prevalence and in
vitro susceptibility of enterococci and VRE among bloodstream infections in
European and US hospitals over time. METHODS: Isolates recovered from the blood
of infected patients in Europe (72 996) and the USA (67 725) between 2001 and
2014 were included in the prevalence analysis. A subset (2349) collected during
2011-13 was used for the in vitro activity analysis. RESULTS: Enterococcus
faecium rates increased in Europe (from 1.4% in 2001 to 4.3% in 2014). These
rates also increased in the USA (from 3.0% in 2001 to 5.4% in 2010), with
decreasing prevalence (4.6% in 2011 to 3.6% in 2014) in later years. Enterococcus
faecalis rates remained stable in Europe, but rose in the USA from 6.9% in 2001
to 8.8% in 2009, declining later (from 7.4% to 5.0%). VRE rates among E. faecalis
did not vary in either region, while VRE rates among E. faecium increased in
Europe (from 4.7% to 20.3%). US VRE rates among E. faecium increased until 2010
(60.0% in 2001 to 80.7% in 2010), decreasing from 75.1% in 2011 to 68.4% in 2013.
Oritavancin demonstrated activity against vancomycin-susceptible E. faecalis
(MIC50/90, 0.015/0.06 mg/L; 99.5% susceptible) and vancomycin-resistant E.
faecalis (MIC50/90, 0.25/0.5 mg/L). Oritavancin showed MIC50, MIC90 and MIC100
values of 0.03, 0.12 and 0.25 mg/L, respectively, for VanA E. faecium.
CONCLUSIONS: Rates of E. faecium and VRE increased in Europe. Although still
elevated, VRE rates appeared to show a decreasing trend in the USA since 2010.
Oritavancin demonstrated activity against enterococci, including VRE.
PMID- 27609053
TI - [Use of indocyanine green angiography in reconstructive surgery: Brief review].
AB - BACKGROUND: The success of flap surgery is highly dependant of vascularisation,
according to the principle of dermal and subdermal perfusion. This principle
requires compatible dimensions for the survival of the flap. Indocyanine green
angiography (ICG), a technique enabling an assessment of vascularization by
fluorescence, has received a considerable impetus during the last two decades.
The purpose of this article was to conduct a review on this technique and to
evaluate its relevance in flap surgery. METHOD: We reviewed all articles
referenced on PubMed from 1995 till 2015 using a search combining the terms
'indocyanine green', 'flap', 'near-infrared', 'fluorescence', 'imaging' OR
'angiography'. RESULTS: One hundred fifty five articles were found and among
those thirty-four were selected. ICG is a reliable technique to locate perforants
vessels, to determine the outlines of the flat and evaluate its per- and
postoperative viability and to appraise anastomoses. CONCLUSION: This technique
allows a reliable and real-time assessment of potential necrotic areas and an
improvement in the detection of complications compared to conventional
techniques.
PMID- 27609054
TI - Surveillance for malaria outbreak on malaria-eliminating islands in Tafea
Province, Vanuatu after Tropical Cyclone Pam in 2015.
AB - The risk of malaria outbreak surfaced in Vanuatu after Tropical Cyclone (TC) Pam
in March 2015. In June and July 2015 we conducted malariometric surveys on the
islands of Tanna, Aneityum, and Erromango in Tafea Province, where malaria
elimination had been targeted, to determine if malaria incidence had increased
after TC Pam. No Plasmodium infection was detected by microscopy and PCR in 3009
survey participants. Only 6.3% (190/3007) of participants had fever. Spleen rates
in children aged ?12 years from Aneityum and Tanna were low, at 3.6% (14/387) and
5.3% (27/510), respectively. Overall bed net use was high at 72.8% (2175/2986);
however, a significantly higher (P < 0.001) proportion of participants from
Aneityum (85.9%, 796/927) reported net use than those from Tanna (67.1%,
751/1119) and Erromango (66.8%, 628/940). A recent decrease in malaria incidence
in Tafea Province through comprehensive intervention measures had reduced the
indigenous parasite reservoir and limited the latter's potential to spur an
outbreak after TC Pam. The path towards malaria elimination in Tafea Province was
not adversely affected by TC Pam.
PMID- 27609051
TI - Population pharmacokinetics of micafungin in ICU patients with sepsis and
mechanical ventilation.
AB - OBJECTIVES: To identify the factors associated with the interindividual
pharmacokinetic (PK) variability of micafungin and to evaluate the probability of
reaching the previously determined PK/pharmacodynamic efficacy thresholds
(AUC/MIC >5000 for non-parapsilosis Candida sp. and >=285 for Candida
parapsilosis) with the recommended 100 mg daily dose in ICU patients with sepsis
and mechanical ventilation. METHODS: One hundred patients were included and 436
concentrations were available for PK analysis performed with NONMEM software. PTA
was determined by Monte Carlo simulations. RESULTS: Micafungin obeyed a two
compartment model with first-order elimination from the central compartment. Mean
parameter estimates (percentage interindividual variability) were 1.34 L/h (34%)
for clearance (CL), 11.80 L (38%) and 7.68 L (39%) for central (Vc) and
peripheral (Vp) distribution volumes, respectively, and 4.67 L/h (37%) for
distribution clearance. CL, Vc and Vp increased by 14% when the albumin level was
<=25 g/L and CL decreased by 25% when SOFA score was >=10. Body weight was
related to CL, Vc and Vp by allometric models. PTA was >=90% in Candida albicans
and Candida glabrata infections, except when the MIC was >=0.015 mg/L, and ranged
between 0% and 40% for C. parapsilosis infections with MIC >=0.5 mg/L.
CONCLUSIONS: A possible increase in the dose should be evaluated for infections
due to C. parapsilosis and for infections due to C. albicans and C. glabrata with
MICs >=0.015 mg/L.
PMID- 27609055
TI - Gammaproteobacteria as essential primary symbionts in the striped shield bug,
Graphosoma Lineatum (Hemiptera: Pentatomidae).
AB - Many members of suborder Heteroptra harbor heritable symbiotic bacteria. Here we
characterize the gut symbiotic bacterium in Graphosoma lineatum (Hemiptera:
Pentatomidae) by using molecular phylogeny, real-time PCR analysis as well as
light and electron microscopy observations. The microscopy observations revealed
the presence of a large number of rod-shaped bacterial cells in the crypts. A
very high prevalence (98 to 100%) of the symbiont infection was found in the
insect populations that strongly supports an intimate association between these
two organisms. Real-time PCR analysis also showed that the Gammaproteobacteria
dominated the crypts. The sequences of 16sr RNA and groEL genes of symbiont
showed high levels of similarity (93 to 95%) to Pantoea agglomeranse and Erwinia
herbicola Gammaproteobacteria. Phylogenetic analyses placed G. lineatum symbiont
in a well-defined branch, divergent from other stink bug bacterial symbionts. Co
evolutionary analysis showed lack of host-symbiont phylogenetic congruence.
Surface sterilization of eggs resulted in increased pre-adult stage in the
offspring (aposymbionts) in comparison to the normal. Also, fecundity, longevity,
and adult stage were significantly decreased in the aposymbionts. Therefore, it
seems that the symbiont might play a vital function in the host biology, in which
host optimal development depends on the symbiont.
PMID- 27609056
TI - The double burden of disease among mining workers in Papua, Indonesia: at the
crossroads between Old and New health paradigms.
AB - BACKGROUND: As the global shift toward non-communicable diseases overlaps with
the unfinished agenda of confronting infectious diseases in low- and middle
income countries, epidemiological links across both burdens must be recognized.
This study examined the non-communicable disease-infectious disease overlap in
the specific comorbidity rates for key diseases in an occupational cohort in
Papua, Indonesia. METHODS: Diagnosed cases of ischaemic heart disease, stroke,
hypertension, diabetes (types 1 and 2), chronic obstructive pulmonary disease,
asthma, cancer, HIV and AIDS, tuberculosis, and malaria were extracted from
22,550 patient records (21,513 men, 1037 women) stored in identical electronic
health information systems from two clinic sites in Papua, Indonesia. Data were
collected as International Classification of Diseases, 10th Revision, entries
from records spanning January-December 2013. A novel application of Circos
software was used to visualize the interconnectedness between the disease burdens
as overlapping prevalence estimates representing comorbidities. RESULTS: Overall,
NCDs represented 38 % of all disease cases, primarily in the form of type 2
diabetes (n = 1440) and hypertension (n = 1398). Malaria cases represented the
largest single portion of the disease burden with 5310 recorded cases, followed
by type 2 diabetes with 1400 cases. Tuberculosis occurred most frequently
alongside malaria (29 %), followed by chronic obstructive pulmonary disease (19
%), asthma (17 %), and stroke (12 %). Hypertension-tuberculosis (4 %),
tuberculosis-cancer (4 %), and asthma-tuberculosis (2 %) comorbidities were also
observed. CONCLUSIONS: The high prevalence of multimorbidity, preponderance of
non-communicable diseases, and extensive interweaving of non-communicable and
infectious disease comorbidities highlighted in this cohort of mining workers in
Papua, Indonesia reflect the markedly double disease burden increasingly plaguing
Indonesia and other similar low- and middle-income countries - a challenge with
which their over-stretched, under-resourced health systems are ill-equipped to
cope. Integrated, person-centered treatment and control strategies rooted in the
primary healthcare sector will be critical to reverse this trend.
PMID- 27609057
TI - Protective Effects of Genistein and Puerarin against Chronic Alcohol-Induced
Liver Injury in Mice via Antioxidant, Anti-inflammatory, and Anti-apoptotic
Mechanisms.
AB - This study aimed to investigate the protective effect of genistein or puerarin on
chronic alcohol-induced liver injury in vivo and to explore the underlying
mechanisms of hepatoprotective effects. Mice were administered genistein or
puerarin (0.3 mmol kg(-1) body weight) and gastrically infused with 50% alcohol
once per day for 5 weeks. Levels of serum transaminases, serum and hepatic
lipids, hepatic antioxidant capacities, inflammation, apoptosis, and
histopathological sections were analyzed. Results showed that genistein and
puerarin exhibited similar effects in ameliorating alcohol-induced liver injury.
However, genistein is more effective than puerarin in decreasing levels of
malondialdehyde (1.05 +/- 0.0947 vs 1.28 +/- 0.213 nmol/mg pro, p < 0.05), tumor
necrosis factor alpha (3.12 +/- 0.498 vs 3.82 +/- 0.277 pg/mg pro, p < 0.05),
interleukin-6 (1.46 +/- 0.223 vs 1.88 +/- 0.309 pg/mg pro, p < 0.05), whereas
puerarin is more effective than genistein in ameliorating serum activities or
levels of alanine transaminase (35.8 +/- 3.95 vs 42.6 +/- 6.56 U/L, p < 0.05) and
low-density lipoprotein cholesterol (1.12 +/- 0.160 vs 1.55 +/- 0.150 mmol/L, p <
0.05). In conclusion, both genistein and puerarin effectively alleviate hepatic
damage induced by chronic alcohol administration through potential antioxidant,
anti-inflammatory, or anti-apoptotic mechanisms.
PMID- 27609059
TI - A cross-sectional assessment of food- and nutrient-based standards applied to
British schoolchildren's packed lunches.
AB - OBJECTIVE: In England, standards for school meals included both foods and
nutrients until 2015. School policies for packed lunches are generally food
based; research is needed to determine whether these are adequate or whether a
small number of nutrients would potentially improve their quality. DESIGN: From
dietary data obtained using a weighed dietary assessment tool, a diet quality
score (DQS) for packed lunches was calculated using the number of standards met
out of twenty-one (eight foods and thirteen nutrients). Multilevel regression
analysis determined the foods and nutrients contributing to variation in the DQS.
SETTING: Eighty-nine primary schools across the four regions of the UK (England,
Wales, Scotland and Northern Ireland). SUBJECTS: British schoolchildren (n 1294),
aged 8-9 years, taking a packed lunch. RESULTS: The optimal model included all
eight foods and seven of the thirteen nutrients, explaining 72 % of the variance
in DQS. Folate, Fe and vitamin C, together with the eight food groups, explained
70 % of DQS variation. CONCLUSIONS: Ideally, policies for school packed lunches
should include food-based standards plus recommendations based on a small number
of nutrients.
PMID- 27609058
TI - Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing
surgical options for upper compartment (vault or uterine) pelvic organ prolapse
(the VUE Study): study protocol for a randomised controlled trial.
AB - BACKGROUND: One in three women who have a prolapse operation will go on to have
another operation, though not necessarily in the same compartment. Surgery can
result in greater impairment of quality of life than the original prolapse itself
(such as the development of new-onset urinary incontinence, or prolapse at a
different site). Anterior and posterior prolapse surgery is most common (90 % of
operations), but around 43 % of women also have a uterine (34 %) or vault (9 %)
procedure at the same time. There is not enough evidence from randomised
controlled trials (RCTs) to guide management of vault or uterine prolapse. The
Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the
surgical management of upper compartment pelvic organ prolapse (POP) in terms of
clinical effectiveness, cost-effectiveness and adverse events. METHODS/DESIGN:
VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault
Trial). Eligible for inclusion are women with vault or uterine prolapse:
requiring a surgical procedure, suitable for randomisation and willing to be
randomised. Randomisation will be computer-allocated separately for each trial,
minimised on: requiring concomitant anterior and/or posterior POP surgery or not,
concomitant incontinence surgery or not, age (under 60 years or 60 years and
older) and surgeon. Participants will be randomly assigned, with equal
probability to intervention or control arms in either the Uterine Trial or the
Vault Trial. Uterine Trial participants will receive either a vaginal
hysterectomy or a uterine preservation procedure. Vault Trial participants will
receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy.
Participants will be followed up by postal questionnaires (6 months post surgery
and 12 months post randomisation) and also reviewed in clinic 12 months post
surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse
Symptom Score (POP-SS) at 12 months post randomisation. DISCUSSION: Demonstrating
the efficacy of vault and uterine prolapse surgeries is relevant not only to
patients and clinicians but also to health care providers, both in the UK and
globally. TRIAL REGISTRATION: Current controlled trials ISRCTN86784244 (assigned
19 October 2012), and the first subject was randomly assigned on 1 May 2013.
PMID- 27609060
TI - [Formula: see text]Selecting measures for the neurodevelopmental assessment of
children in low- and middle-income countries.
AB - Diseases affecting millions of children in low- and middle-income countries
(LMICs), such as malnutrition, micronutrient deficiency, malaria, and HIV, can
lead to adverse neurodevelopmental outcomes. Thus, a key health outcome in
children is neurodevelopmental status. In this paper, the neurodevelopmental
screening and testing measures most commonly utilized in LMICs are reviewed, and
a matrix is presented to help researchers and clinicians determine which measures
may be most useful for various LMIC inquiries. The matrix is based on an Internet
literature review of 114 publications for the period January 1998 to February
2016, reporting the psychometric properties of instruments tested in LMIC
children. The measures are classified as screening tests or more detailed tests
that include both comprehensive batteries of general development and tests of
specific domains. For completeness, two experts have reviewed this paper, as well
as the authors. An overview of the tests used to date is presented, including the
benefits and drawbacks of each test, in order to provide researchers and
developmental clinicians with a way to decide which tests may be best suited to
their developmental assessment goals. Remarkable progress has been made in
neurodevelopmental testing in children in LMICs over the past two decades but
there remains a need for additional research in this area to develop new tests,
better evaluate and adapt current tests, and assess test validity and reliability
across cultures.
PMID- 27609063
TI - Confirmatory analysis of etanercept in equine plasma by LC-MS for doping control.
AB - Etanercept is a protein-based medication for the treatment of human patients with
rheumatoid arthritis and other autoimmune-based diseases; its pharmacological
action is to inhibit and antagonize tumour necrosis factor alpha. Etanercept was
rumoured to be used in horse racing in North America. To detect such use, the aim
of this study was to develop a liquid chromatography-mass spectrometry (LC-MS)
method for confirmation of etanercept in equine plasma. Etanercept was extracted
from plasma by anti-human IgG antibody linked to magnetic beads. The analyte was
reduced and alkylated, and then digested by trypsin. Tryptic peptides (T1 from
human tumour necrosis factor receptor 2 of etanercept, T15 and T27 from human
IgG1 of the protein) were employed for detection and confirmation of the analyte.
The limit of detection was 5 ng/mL, and the limit of confirmation 10 ng/mL. This
method is specific for confirmation of etanercept, as assessed using the results
from BLAST and SEQUEST searches. The results from SEQUEST searches also revealed
an unexpected unique specificity of product ion spectrum of IgG1 T27 with only a
single product ion for identification of etanercept. It is the first report for
such a finding, to the authors' knowledge. The method was successful in analyses
of the plasma samples collected post administration of etanercept to horses.
Etanercept was detected up to 11 days post administration. This method will be
helpful for confirmation of etanercept or other protein-based drugs consisting of
human IgG1, in equine drug testing. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27609062
TI - Model-based variables for the kinematic assessment of upper-extremity impairments
in post-stroke patients.
AB - BACKGROUND: Common scales for clinical evaluation of post-stroke upper-limb motor
recovery are often complemented with kinematic parameters extracted from movement
trajectories. However, there is no a general consensus on which parameters to
use. Moreover, the selected variables may be redundant and highly correlated or,
conversely, may incompletely sample the kinematic information from the
trajectories. Here we sought to identify a set of clinically useful variables for
an exhaustive but yet economical kinematic characterization of upper limb
movements performed by post-stroke hemiparetic subjects. METHODS: For this
purpose, we pursued a top-down model-driven approach, seeking which kinematic
parameters were pivotal for a computational model to generate trajectories of
point-to-point planar movements similar to those made by post-stroke subjects at
different levels of impairment. RESULTS: The set of kinematic variables used in
the model allowed for the generation of trajectories significantly similar to
those of either sub-acute or chronic post-stroke patients at different time
points during the therapy. Simulated trajectories also correctly reproduced many
kinematic features of real movements, as assessed by an extensive set of
kinematic metrics computed on both real and simulated curves. When inspected for
redundancy, we found that variations in the variables used in the model were
explained by three different underlying and unobserved factors related to
movement efficiency, speed, and accuracy, possibly revealing different working
mechanisms of recovery. CONCLUSION: This study identified a set of measures
capable of extensively characterizing the kinematics of upper limb movements
performed by post-stroke subjects and of tracking changes of different motor
improvement aspects throughout the rehabilitation process.
PMID- 27609061
TI - The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of
experimental necrotising enterocolitis by enhancing mesenteric perfusion in the
neonatal intestine.
AB - Necrotising enterocolitis (NEC) is a common disease in premature infants
characterised by intestinal ischaemia and necrosis. The only effective
preventative strategy against NEC is the administration of breast milk, although
the protective mechanisms remain unknown. We hypothesise that an abundant human
milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects
against NEC by enhancing intestinal mucosal blood flow, and we sought to
determine the mechanisms underlying this protection. Administration of HMO-2'FL
protected against NEC in neonatal wild-type mice, resulted in a decrease in pro
inflammatory markers and preserved the small intestinal mucosal architecture.
These protective effects occurred via restoration of intestinal perfusion through
up-regulation of the vasodilatory molecule endothelial nitric oxide synthase
(eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that
received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO
2'FL affected the microbiota of the neonatal mouse gut, although these changes do
not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL
was also observed in cultured endothelial cells, providing a link between eNOS
and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against
NEC in part through maintaining mesenteric perfusion via increased eNOS
expression, and suggest that the 2'FL found in human milk may be mediating some
of the protective benefits of breast milk in the clinical setting against NEC.
PMID- 27609064
TI - Bacterial hybrid histidine kinases in plant-bacteria interactions.
AB - Two-component signal transduction systems are essential for many bacteria to
maintain homeostasis and adapt to environmental changes. Two-component signal
transduction systems typically involve a membrane-bound histidine kinase that
senses stimuli, autophosphorylates in the transmitter region and then transfers
the phosphoryl group to the receiver domain of a cytoplasmic response regulator
that mediates appropriate changes in bacterial physiology. Although usually found
on distinct proteins, the transmitter and receiver modules are sometimes fused
into a so-called hybrid histidine kinase (HyHK). Such structure results in
multiple phosphate transfers that are believed to provide extra-fine-tuning
mechanisms and more regulatory checkpoints than classical phosphotransfers. HyHK
based regulation may be crucial for finely tuning gene expression in a
heterogeneous environment such as the rhizosphere, where intricate plant-bacteria
interactions occur. In this review, we focus on roles fulfilled by bacterial
HyHKs in plant-associated bacteria, providing recent findings on the mechanistic
of their signalling properties. Recent insights into understanding additive
regulatory properties fulfilled by the tethered receiver domain of HyHKs are also
addressed.
PMID- 27609065
TI - Comparison of trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin
abscesses.
AB - : Clinical question In patients with uncomplicated abscesses receiving incision
and drainage, does the addition of trimethoprim-sulfamethoxazole result in
improved clinical resolution at 7 to 14 days after treatment when compared with
placebo? Article chosen Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim
sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med
2016;374(9):823-32. OBJECTIVE: The primary objective of this study was to compare
the clinical cure rates at 7 to 14 days after the end of the treatment period
among patients receiving either trimethoprim-sulfamethoxazole (TMP-SMX) or
placebo. Secondary outcomes included composite cure; surgical drainage
procedures; change in erythema size; presence of swelling, induration, or
tenderness; invasive infections; skin infections at the same site and different
sites; hospitalizations; similar infections in household contacts; days missed
from normal activities; days missed from school or work; and days of analgesic
use.
PMID- 27609066
TI - The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to
enhance the growth of hepatoma cells.
AB - Hepatitis B X-interacting protein (HBXIP) as an oncoprotein plays crucial roles
in the development of cancer, involving glucose metabolism reprogramming. In this
study, we are interested in whether the oncoprotein HBXIP is involved in the
modulation of gluconeogenesis in liver cancer. Here, we showed that the
expression level of phosphoenolpyruvate carboxykinase (PCK1), a key enzyme of
gluconeogenesis, was lower in clinical hepatocellular carcinoma (HCC) tissues
than that in normal tissues. Mechanistically, HBXIP inhibited the expression of
PCK1 through down-regulating transcription factor FOXO1 in hepatoma cells, and up
regulated miR-135a targeting the 3'UTR of FOXO1 mRNA in the cells. In addition,
HBXIP increased the phosphorylation levels of FOXO1 protein by activating
PI3K/Akt pathway, leading to the export of FOXO1 from nucleus to cytoplasm.
Strikingly, over-expression of PCK1 could abolish the HBXIP-promoted growth of
hepatoma cells in vitro and in vivo. Thus, we conclude that the oncoprotein HBXIP
is able to depress the gluconeogenesis through suppressing PCK1 to promote
hepatocarcinogenesis, involving miR-135a/FOXO1 axis and PI3K/Akt/p-FOXO1 pathway.
Our finding provides new insights into the mechanism by which oncoprotein HBXIP
modulates glucose metabolism reprogramming in HCC.
PMID- 27609067
TI - The repopulating cancer cells in melanoma are characterized by increased
mitochondrial membrane potential.
AB - Although considerable effort has been expended in identifying definitive markers
for cancer stem cells (CSCs) or cancer-initiating cells (CICs), the phenotypic
plasticity of these cells obviates simple characterization using cell surface
markers. We hypothesized that these cells could be characterized by their
metabolic properties because they are in a quiescent state with low energy needs.
We examined whether cancer cells differ in mitochondrial membrane potential
(Deltapsim) when they are under stress. The Deltapsim of B16-F10 melanoma cells
increased when they were exposed in vitro to serum starvation and
chemotherapeutic agents, but not when exposed to hypoxia. Such TMREhigh cells
were also present in tumor tissue. They primarily used glucose and/or lactate,
and were superior to TMRElow B16-F10 cells in their ability to drive tumor
growth. These findings suggest that CSCs or CICs could be identified in
heterogeneous melanoma populations by measuring Deltapsim.
PMID- 27609068
TI - Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced
apoptosis by regulating the miR-645-IFIT2 axis.
AB - Chemotherapeutic insensitivity remains a major obstacle to osteosarcoma
treatment. Recently, increasing evidence has suggested that long non-coding RNAs
(lncRNAs) play an essential role in tumourigenesis. However, the potential
biological roles and regulatory mechanisms of novel lncRNAs in response to
cisplatin treatment are poorly understood. Here, we found that lncRNA LINC00161
was induced by cisplatin in osteosarcoma cells. Elevated LINC00161 increased
cisplatin-induced apoptosis and reversed the cisplatin-resistant phenotype of
osteosarcoma cells by upregulating IFIT2. Further mechanistic studies revealed
that LINC00161 could sponge endogenous miR-645 and inhibit its activity leading
to IFIT2 increase. In addition, we identified that LINC00161 enhanced cisplatin
induced apoptosis through regulation of the miR-645-IFIT2 pathway. Thus, these
findings demonstrate that LINC00161 is an essential regulator in cisplatin
induced apoptosis, and the LINC00161-miR-645-IFIT2 signalling axis plays an
important role in reducing osteosarcoma chemoresistance.
PMID- 27609069
TI - A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the
prioritization of therapeutic targets.
AB - Although cancer-associated fibroblasts (CAFs) are viewed as a promising
therapeutic target, the design of rational therapy has been hampered by two key
obstacles. First, attempts to ablate CAFs have resulted in significant toxicity
because currently used biomarkers cannot effectively distinguish activated CAFs
from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second,
it is unclear whether CAFs in different organs have different molecular and
functional properties that necessitate organ-specific therapeutic designs. Our
analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs.
Using COL11A1 as a 'seed', we identified co-expressed genes in 13 types of
primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular
signature of activated CAFs is conserved in epithelial cancers regardless of
organ site and transforming events within cancer cells, suggesting that targeting
fibroblast activation should be effective in multiple cancers. We prioritized
several potential pan-cancer therapeutic targets that are likely to have high
specificity for activated CAFs and minimal toxicity in normal tissues.
PMID- 27609072
TI - Best Practices for Treatment of Invasive Methicillin-Susceptible Staphylococcus
aureus Infections: The Case for Oxacillin.
PMID- 27609073
TI - Oromotor Feeding in Children Born Before 30 Weeks' Gestation and Term-Born Peers
at 12 Months' Corrected Age.
AB - OBJECTIVES: To evaluate oromotor feeding at 12 months' corrected age in children
born before 30 weeks' gestational age compared with term-born peers by the use of
observational assessment and to examine predictors of oromotor feeding
difficulties in children born before 30 weeks. STUDY DESIGN: Oromotor feeding was
assessed at 12 months' corrected age with the Schedule for Oral Motor Assessment
in 90 children born before 30 weeks and 137 term-born children. Feeding outcomes
were compared between groups. Sex, gestational age at birth, birth weight, social
risk, history of tube feeding, surgery, and respiratory support were analyzed as
potential risk factors. RESULTS: At 12 months' corrected age, 38% of children
born before 30 weeks had oromotor feeding difficulties-with greater odds of
difficulties than term-born participants (OR 2.21; 95% CI 1.55-3.16).
Difficulties were observed with specific food textures (purees, solids, crackers)
and areas of oromotor skill (lip and jaw movement, food loss, swallowing).
Neonatal surgery (n = 4/89) appeared to be the only predictor of oromotor feeding
issues (OR 11.66; 95% CI 1.56-87.23; P = .02). CONCLUSIONS: Children born before
30 weeks presented with greater odds of oromotor feeding problems at 12 months'
corrected age than their term-born peers. Neonatal surgery was associated with
increased odds of feeding difficulties in children born before 30 weeks.
Surveillance and support of oromotor feeding skills for very preterm children is
indicated, particularly during their transition to solid foods.
PMID- 27609070
TI - Workplace health promotion for older workers: a systematic literature review.
AB - BACKGROUND: Aging of the workforce is a growing problem. As workers age, their
physical, physiological and psychosocial capabilities change. Keeping older
workers healthy and productive is a key goal of European labor policy and health
promotion is a key to achieve this result. Previous studies about workplace
health promotion (WHP) programs are usually focused on the entire workforce or to
a specific topic. Within the framework of the EU-CHAFEA ProHealth65+ project,
this paper aims to systematically review the literature on WHP interventions
specifically targeted to older workers (OWs). METHODS: This systematic review was
conducted by making a comprehensive search of MEDLINE, ISI Web of Science,
SCOPUS, The Cochrane Library, CINAHL and PsychINFO databases. Search terms
included ageing (and synonyms), worker (and synonyms), intervention (and
synonyms), and health (and synonyms). The search was limited to papers in English
or Italian published between January, 1(st) 2000 and May, 31(st) 2015. Relevant
references in the selected articles were also analyzed. RESULTS: Of the 299
articles initially identified as relating to the topic, 18 articles met the
inclusion criteria. The type, methods and outcome of interventions in the WHP
programs retrieved were heterogenous, as was the definition of the age at which a
worker is considered to be 'older'. Most of the available studies had been
conducted on small samples for a limited period of time. CONCLUSION: Our review
shows that, although this issue is of great importance, studies addressing WHP
actions for OWs are few and generally of poor quality. Current evidence fails to
show that WHP programs improve the work ability, productivity or job retention of
older workers. In addition, there is limited evidence that WHP programs are
effective in improving lifestyles and concur to maintain the health and well
being of older workers. There is a need for future WHP programs to be well
designed so that the effectiveness and cost-benefit of workplace interventions
can be properly investigated.
PMID- 27609074
TI - "Unavoidable Satisfactions": The Analyst's Pleasure.
AB - Analysts have often described their work as depriving, painful, and hard to
endure, while its pleasures have been the subject of little commentary. The real
history and ongoing temptations of boundary violation long ago made the
gratifications of psychoanalytic work a matter of anxiety. Analysts' pleasure in
their work was problematized. Some of this problematizing is necessary because of
real risk, but much of it is not only unnecessary but misleading and destructive.
Psychoanalysts pursue achievement of a unique form of human intimacy, yet
acquired habits of professional modesty and humility have encouraged the illusion
that analyzing can occur without desire or ambition on the analyst's part. These
habits have made it difficult for analysts to openly discuss what they get from
the intimacy of analyzing that yields its pleasures. Our field demands that
analysts deny that the work provides much more than pain (at least until the
conclusion of an analysis), but psychoanalysis both misunderstands and
misrepresents itself if we cannot speak of the distinctly broad range of
pleasures available in analyzing.
PMID- 27609071
TI - Increased phosphorylation of collapsin response mediator protein-2 at Thr514
correlates with beta-amyloid burden and synaptic deficits in Lewy body dementias.
AB - Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone
extension, and increased CRMP2 phosphorylation may lead to axonal degeneration.
Axonal and synaptic pathology is an important feature of Lewy body dementias
(LBD), but the state of CRMP2 phosphorylation (pCRMP2) as well as its
correlations with markers of neurodegeneration have not been studied in these
dementias. Hence, we measured CRMP2 phosphorylation at Thr509, Thr514 and Ser522,
as well as markers of beta-amyloid (Abeta), tau-phosphorylation, alpha-synuclein
and synaptic function in the postmortem neocortex of a longitudinally assessed
cohort of LBD patients characterized by low (Parkinson's disease dementia, PDD)
and high (dementia with Lewy bodies, DLB) burden of Alzheimer type pathology. We
found specific increases of pCRMP2 at Thr514 in DLB, but not PDD. The increased
CRMP2 phosphorylation correlated with fibrillogenic Abeta as well as with losses
of markers for axon regeneration (beta-III-tubulin) and synaptic integrity
(synaptophysin) in LBD. In contrast, pCRMP2 alterations did not correlate with
tau-phosphorylation or alpha-synuclein, and also appear unrelated to
immunoreactivities of putative upstream kinases glycogen synthase kinase 3beta
and cyclin-dependent kinase 5, as well as to protein phosphatase 2A. In
conclusion, increased pCRMP2 may underlie the axonal pathology of DLB, and may be
a novel therapeutic target. However, antecedent signaling events as well as the
nature of pCRMP2 association with Abeta and other neuropathologic markers require
further study.
PMID- 27609076
TI - Slouching Towards Mortality: Thoughts on Time and Death.
PMID- 27609075
TI - Working Through the "Caesura": A Clinical Illustration.
AB - More and more often analysts work with patients who must develop the capacity to
participate in analysis. One such patient, H., conveyed the impression of being
"bogged down." He did not work or study, and at home with his family was prone to
violent outbursts; his social relationships were centered around drug use.
Concepts from Bion and Winnicott helped H.'s analyst take the risks necessary to
create a therapeutic relationship with him. The patient has come to realize the
worth of analytic thinking, and its potential to transform his life. Deviance
with respect to technique, and collusion between the narcissistic areas of
therapist and patient, pose the risk of dangerous slips in the direction of
analytic "omnipotence." Reclaiming the term collusion (from the Latin con-ludere,
"to play together"), however, can allow analysts to remain faithful to Freud's
ideas while maintaining a necessary flexibility vis-a-vis the patient. This ludic
space can be expanded through Bion's ideas, which deconstruct a perspective
through which we are able to observe "facts," with particular reference to what
occurs in the psychoanalytic situation.
PMID- 27609077
TI - Journal Watch review of Maternal attachment representation and neurophysiological
processing during the perception of infants' emotional expressions.
PMID- 27609078
TI - Journal Watch review of The social origins of sustained attention in one-year-old
human infants.
PMID- 27609079
TI - Journal Watch review of Oxytocin and memory of emotional stimuli: Some dance to
remember, some dance to forget.
PMID- 27609081
TI - Training Analysts at William Alison White.
PMID- 27609082
TI - Using Heidegger.
PMID- 27609083
TI - Effects of excess metabolizable protein on ovarian function and circulating amino
acids of beef cows: 2. Excessive supply in varying concentrations from corn
gluten meal.
AB - In the dairy industry, excess dietary CP is consistently correlated with
decreased conception rates. However, amount of excess CP effects on reproductive
function in beef cattle is largely undefined. The objective of this experiment
was to determine the effects of excess metabolizable protein (MP) supplementation
from a moderately abundant rumen undegradable protein (RUP) source (corn gluten
meal: 62% RUP) on ovarian function and circulating amino acid (AA) concentrations
in beef cows consuming low quality forage. Non-pregnant, non-lactating beef cows
(n=16) were allocated by age, BW and body condition score (BCS) to 1 of 2
isocaloric supplements designed to maintain BW for 60 days. Cows had ad libitum
access to corn stalks and were individually offered a corn gluten meal-based
supplement daily at 125% (MP125) or 150% (MP150) of National Research Council
(NRC) MP requirements. After a 20-day supplement adaptation period, cows were
synchronized for ovulation. After 10 days of synchronization, follicular growth
was reset with gonadotropin releasing hormone. Daily thereafter, transrectal
ultrasonography was performed to diagram ovarian follicular waves, and blood
samples were collected for hormone, metabolite and AA analyses. After 7 days of
observation of estrus, corpus luteum (CL) size was determined via ultrasound.
Data were analyzed using the MIXED procedures of SAS. No differences (P?0.21) in
BW and BCS existed throughout the study; however, plasma urea N at ovulation was
greater (P=0.04) in MP150. Preovulatory ovarian follicle size at dominance,
duration of dominance, size at spontaneous luteolysis, length of proestrus and
wavelength were not different (P?0.11) between treatments. However, ovulatory
follicles were larger (P=0.04) and average antral follicle count was greater
(P=0.01) in MP150 than MP125. Estradiol concentration and ratio of estradiol to
ovulatory follicle volume were not different due to treatment (P?0.25). While CL
volume 7 days post-estrus was greater (P<0.01) in MP150 than MP125, circulating
progesterone 7 days post-estrus and ratio of progesterone to CL volume were not
different (P?0.21). Total AA were not different (P?0.76) at study initiation or
completion; however, as a percent of total AA, branched-chain AA at ovulation
were greater (P=0.02) in MP150. In conclusion, supplementation of CP at 150% of
NRC MP requirements from a moderately undegradable protein source may enhance
growth of the ovulatory follicle and subsequent CL compared with MP
supplementation at 125% of NRC MP requirements.
PMID- 27609084
TI - The efficacy of Schwann cell transplantation on motor function recovery after
spinal cord injuries in animal models: A systematic review and meta-analysis.
AB - AIM: This article aimed to assess the efficacy of Schwann cell transplantation on
motor function recovery in animal model of spinal cord injuries via meta
analysis. METHODS: An extended search was carried out in the electronic databases
of Medline (via PubMed), EMBASE (via OvidSP), CENTRAL, SCOPUS, Web of Science
(BIOSIS), and ProQuest. Finally, 41 eligible studies conducted on 1046 animals
including 517 control animals and 529 transplanted animals were included in the
meta-analysis. Pooled standardized mean difference (SMD) and odds ratio (OR) with
95% confidence interval (95% CI) were reported. RESULTS: The findings showed that
treatment with Schwann cells leads to a modest motor function recovery after
spinal cord injury (SMD=0.85; 95% CI: 0.63-1.07; p<0.001). Transplantation of
these cells in acute phase of the injury (immediately after the injury) (OR=4.30;
95% CI: 1.53-12.05; p=0.007), application of mesenchymal/skin-derived precursors
(OR=2.34; 95% CI: 1.28-4.29; p=0.008), and cells with human sources are
associated with an increase in efficacy of Schwann cells (OR=10.96; 95% CI: 1.49
80.77; p=0.02). Finally, it seems that the efficacy of Schwann cells in mice is
significantly lower than rats (OR=0.03; 95% CI: 0.003-0.41; p=0.009). CONCLUSION:
Transplantation of Schwann cells can moderately improve motor function recovery.
It seems that inter-species differences might exist regarding the efficacy of
this cells. Therefore, this should be taken into account when using Schwann cells
in clinical trials regarding spinal cord injuries.
PMID- 27609085
TI - Comment on "Workplace Bullying as a Risk Factor for Musculoskeletal Disorders:
The Mediating Role of Job-Related Psychological Strain".
PMID- 27609086
TI - Bacteriophages in clinical samples can interfere with microbiological diagnostic
tools.
AB - Bacteriophages are viruses that infect bacteria, and they are found everywhere
their bacterial hosts are present, including the human body. To explore the
presence of phages in clinical samples, we assessed 65 clinical samples (blood,
ascitic fluid, urine, cerebrospinal fluid, and serum). Infectious tailed phages
were detected in >45% of ascitic fluid and urine samples. Three examples of phage
interference with bacterial isolation were observed. Phages prevented the
confluent bacterial growth required for an antibiogram assay when the inoculum
was taken from an agar plate containing lysis plaques, but not when taken from a
single colony in a phage-free area. In addition, bacteria were isolated directly
from ascitic fluid, but not after liquid enrichment culture of the same samples,
since phage propagation lysed the bacteria. Lastly, Gram-negative bacilli
observed in a urine sample did not grow on agar plates due to the high densities
of infectious phages in the sample.
PMID- 27609087
TI - Casitas B-lineage lymphoma linker helix mutations found in myeloproliferative
neoplasms affect conformation.
AB - BACKGROUND: Casitas B-lineage lymphoma (Cbl or c-Cbl) is a RING ubiquitin ligase
that negatively regulates protein tyrosine kinase (PTK) signalling.
Phosphorylation of a conserved residue (Tyr371) on the linker helix region (LHR)
between the substrate-binding and RING domains is required to ubiquitinate PTKs,
thereby flagging them for degradation. This conserved Tyr is a mutational hotspot
in myeloproliferative neoplasms. Previous studies have revealed that select point
mutations in Tyr371 can potentiate transformation in cells and mice but not all
possible mutations do so. To trigger oncogenic potential, Cbl Tyr371 mutants must
perturb the LHR-substrate-binding domain interaction and eliminate PTK
ubiquitination. Although structures of native and pTyr371-Cbl are available, they
do not reveal how Tyr371 mutations affect Cbl's conformation. Here, we
investigate how Tyr371 mutations affect Cbl's conformation in solution and how
this relates to Cbl's ability to potentiate transformation in cells. RESULTS: To
explore how Tyr371 mutations affect Cbl's properties, we used surface plasmon
resonance to measure Cbl mutant binding affinities for E2 conjugated with
ubiquitin (E2-Ub), small angle X-ray scattering studies to investigate Cbl mutant
conformation in solution and focus formation assays to assay Cbl mutant
transformation potential in cells. Cbl Tyr371 mutants enhance E2-Ub binding and
cause Cbl to adopt extended conformations in solution. LHR flexibility, RING
domain accessibility and transformation potential are associated with the extent
of LHR-substrate-binding domain perturbation affected by the chemical nature of
the mutation. More disruptive mutants like Cbl Y371D or Y371S are more extended
and the RING domain is more accessible, whereas Cbl Y371F mimics native Cbl in
solution. Correspondingly, the only Tyr371 mutants that potentiate transformation
in cells are those that perturb the LHR-substrate-binding domain interaction.
CONCLUSIONS: c-Cbl's LHR mutations are only oncogenic when they disrupt the
native state and fail to ubiquitinate PTKs. These findings provide new insights
into how LHR mutations deregulate c-Cbl.
PMID- 27609088
TI - [Extrahepatic and extrapulmonary hydatidosis].
AB - BACKGROUND: Cystic echinococcosis is a zoonosis caused by larvae of the parasite
Echinococcus that is endemic in many countries of the Mediterranean area. It can
affect any organ, with the most common sites being liver (70%) and lung (20%).
Splenic hydatid disease, despite being rare, is the third most common location.
Other locations such as bone, skin, or kidney are exceptional. OBJECTIVE: To
present our experience in extrahepatic and extrapulmonary hydatidosis. MATERIAL
AND METHODS: Period: May 2007-December 2014. Health area: 251,000 inhabitants.
During that period, a total of 136 patients with hydatid disease were evaluated
in our Hepato-pancreatic-biliary Surgery Unit. Extrahepatic and extrapulmonary
hydatid disease was found in 18 (13%) patients. A retrospective review was
performed on all medical records, laboratory results, serology, diagnostic
methods, and therapeutic measurements of all patients. An abdominal ultrasound
and CT, as well as hydatid serology was also performed on all patients. RESULTS:
The mean age of the patients was 44.5 years, with a range of 33-80 years. Half
the patients (50%) had concomitant hepatic echinococcosis. Of the 18 patients
with hydatid disease, 13 underwent surgery (radical surgery in 12 cases), and one
underwent (endoscopic retrograde cholangiopancreatography)+puncture, aspiration,
injection and re-aspiration. The remaining 4did not have surgery due to patient
refusal (3), or advanced cancer (1). No recurrences have been observed.
CONCLUSION: The best surgical treatment in these cases is closed total cystectomy
to prevent recurrence, except in the spleen where splenectomy is preferred.
Conservative techniques are indicated in cases of multiple hydatid disease and in
patients with high surgical risk.
PMID- 27609089
TI - [Persistent elevation of Ca 19-9 and an unexpected finding. A case report].
AB - BACKGROUND: Tumour markers are substances produced by the tumour itself, or by
the host in response to a tumour. These markers could be measured either in the
blood or in body secretions. One of the most common tumour markers used in
gastrointestinal diseases is Ca 19-9. It is the marker most used for pancreatic
cancer, but can be elevated in many benign processes. Thus, it is not a specific
marker. CLINICAL CASE: The case is presented of a male patient with 4 years of
moderate abdominal pain, weight loss, and persistent elevation of Ca 19-9. After
an extensive work-up, renal and hepatic cysts were found, as well as steatosis
and, apparently, a gallbladder polyp. With these findings and the persistent
elevation of Ca 19-9, it was decided to operate the patient. An exploratory
laparoscopy was performed showing multiple, yellowish nodular lesions all over
the hepatic surface suggestive of metastases, as well as simple hepatic cysts.
Pathology reported biliary hamartomas, steatosis, and chronic cholecystitis.
After 2years of follow up, although there is no evidence of malignant neoplasia,
there is still an elevation of Ca 19-9. CONCLUSION: The persistent elevation of
Ca 19-9 is probably due to the presence of multiple benign diseases such as
steatosis, urolithiasis, hepatic and renal cysts, and cholecystitis. An algorithm
is needed for healthy patients with elevated levels of Ca 19-9 marker, in order
to lower costs, avoid misdiagnoses, and improve management.
PMID- 27609091
TI - Cardiovascular magnetic resonance detects the progression of impaired myocardial
perfusion reserve and increased left-ventricular mass in mice fed a high-fat
diet.
AB - BACKGROUND: Impaired myocardial perfusion reserve (MPR) is prevalent in obesity
and diabetes, even in the absence of obstructive coronary artery disease (CAD),
and is prognostic of adverse events. We sought to establish the time course of
reduced MPR and to investigate associated vascular and tissue properties in mice
fed a high-fat diet (HFD), as they are an emerging model of human obesity,
diabetes, and reduced MPR without obstructive CAD. METHODS: C57Bl/6 mice fed a
HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet.
The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine
imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall
thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR.
Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary
density and tissue fibrosis were also assessed. RESULTS: Body weight was
increased in HFD mice at 6-24 weeks post-diet (p < 0.05 vs. control). MPR in HFD
mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24
weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity
to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control).
There were no significant differences in cardiac volumes, EF, or capillary
density measurements between the two groups. Histology showed interstitial
fibrosis in HFD and no aortic atherosclerosis in either group. CONCLUSIONS:
C57Bl/6 mice fed a HFD for 18-24 weeks have progressively increased LV mass and
impaired MPR with fibrosis, normal capillary density and no aortic plaque. These
results establish C57Bl/6 mice fed a HFD for 18-24 weeks as a model of impaired
MPR without obstructive CAD due to obesity and diabetes.
PMID- 27609090
TI - 24-hour-restraint stress induces long-term depressive-like phenotypes in mice.
AB - There is an increasing risk of mental disorders, such as acute stress disorder
(ASD), post-traumatic stress disorder (PTSD) and depression among survivors who
were trapped in rubble during earthquake. Such long-term impaction of a single
acute restraint stress has not been extensively explored. In this study, we
subjected mice to 24-hour-restraint to simulate the trapping episode, and
investigated the acute (2 days after the restraint) and long-term (35 days after
the restraint) impacts. Surprisingly, we found that the mice displayed depression
like behaviors, decreased glucose uptake in brain and reduced adult hippocampal
neurogenesis 35 days after the restraint. Differential expression profiling based
on microarrays suggested that genes and pathways related to depression and other
mental disorders were differentially expressed in both PFC and hippocampus.
Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be
reversed by fluoxetine, a type of antidepressant drug. These findings
demonstrated that a single severe stressful event could produce long-term
depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could
also be used for further studies on mood disorders.
PMID- 27609092
TI - In vivo bioluminescence imaging for leptomeningeal dissemination of
medulloblastoma in mouse models.
AB - BACKGROUND: The primary cause of treatment failure in medulloblastomas (MB) is
the development of leptomeningeal dissemination (seeding). For translational
research on MB seeding, one of the major challenges is the development of
reliable experimental models that simulate the seeding and growth characteristics
of MBs. To overcome this obstacle, we improved an experimental mouse model by
intracisternal inoculation of human MB cells and monitoring with in vivo live
images. METHODS: Human MB cells (UW426, D283 and MED8A) were transfected with a
firefly luciferase gene and a Thy1.1 (CD90.1) marker linked with IRES under the
control of the CMV promoter in a retroviral DNA backbone (effLuc). The MB-effLuc
cells were injected into the cisterna magna using an intrathecal catheter, and
bioluminescence images were captured. We performed histopathological analysis to
confirm the extent of tumor seeding. RESULTS: The luciferase activity of MB
effLuc cells displayed a gradually increasing pattern, which correlated with a
quantitative luminometric assay. Live imaging showed that the MB-effLuc cells
were diffusely distributed in the cervical spinal cord and the lumbosacral area.
All mice injected with UW426-effLuc, D283-effLuc and MED8A-effLuc died within 51
days. The median survival was 22, 41 and 12 days after injection of 1.2 * 10(6)
UW426-effLuc, D283-effLuc and MED8A-effLuc cells, respectively. The
histopathological studies revealed that the MB-effLuc cells spread extensively
and diffusely along the leptomeninges of the brain and spinal cord, forming tumor
cell-coated layers. The tumor cells in the subarachnoid space expressed a human
nuclei marker and Ki-67. Compared with the intracerebellar injection method in
which the subfrontal area and distal spinal cord were spared by tumor cell
seeding in some mice, the intracisternal injection model more closely resembled
the widespread leptomeningeal seeding observed in MB patients. CONCLUSION: The
results and described method are valuable resources for further translational
research to overcome MB seeding.
PMID- 27609093
TI - Molecular characterization and expression analysis of three novel autophagy
related genes from the cattle tick Rhipicephalus (Boophilus) microplus (Acari:
Ixodidae).
AB - The cattle tick Rhipicephalus (Boophilus) microplus is a hematophagous
ectoparasite of major importance for the livestock industry. It shows a
remarkable ability to survive over long periods without feeding. However, the
mechanisms used to endure long-term starvation are poorly understood. It is
believed that autophagy, a process of intracellular protein degradation, may play
a significant role to confront adverse environmental conditions. To advance our
understanding of autophagy in R. microplus, in the present study we report the
molecular characterization of three autophagy-related (ATG) genes, namely,
RmATG3, RmATG4 and RmATG6, as well as their expression profiles in different
developmental stages and organs of the parasite. The deduced amino acid sequences
derived from the characterized gene sequences were subjected to Basic Local
Alignment Search Tool analysis. The testing produced significant alignments with
respective ATG proteins from Haemaphysalis longicornis and Ixodes scapularis
ticks. Real-time polymerase chain reaction assays revealed that RmATG4 and RmATG6
transcripts were elevated in egg and ovary tissue, when compared with larva and
midgut samples, while RmATG3 expression in midgut was 2-fold higher than in egg,
larva and ovary samples.
PMID- 27609094
TI - Anodic biofilms as the interphase for electroactive bacterial growth on carbon
veil.
AB - The structure and activity of electrochemically active biofilms (EABs) are
usually investigated on flat electrodes. However, real world applications such as
wastewater treatment and bioelectrosynthesis require tridimensional electrodes to
increase surface area and facilitate EAB attachment. The structure and activity
of thick EABs grown on high surface area electrodes are difficult to characterize
with electrochemical and microscopy methods. Here, the authors adopt a stacked
electrode configuration to simulate the high surface and the tridimensional
structure of an electrode for large-scale EAB applications. Each layer of the
stacked electrode is independently characterized using confocal laser scanning
microscopy (CLSM) and digital image processing. Shewanella oneidensis MR-1
biofilm on stacked carbon veil electrodes is grown under constant oxidative
potentials (0, +200, and +400 mV versus Ag/AgCl) until a stable current output is
obtained. The textural, aerial, and volumetric parameters extracted from CLSM
images allow tracking of the evolution of morphological properties within the
stacked electrodes. The electrode layers facing the bulk liquid show higher
biovolumes compared with the inner layer of the stack. The electrochemical
performance of S. oneidensis MR-1 is directly linked to the overall biofilm
volume as well as connectivity between cell clusters.
PMID- 27609095
TI - Furfuryl methacrylate plasma polymers for biomedical applications.
AB - Furfuryl methacrylate (FMA) is a promising precursor for producing polymers for
biomedical and cell therapy applications. Herein, FMA plasma polymer coatings
were prepared with different powers, deposition times, and flow rates. The plasma
polymer coatings were characterized using atomic force microscopy (AFM), scanning
electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS), and time-of
flight secondary ion mass spectrometry (ToF-SIMS). The results from AFM and SEM
show the early growth of the coatings and the existence of particle aggregates on
the surfaces. XPS results indicated no measureable chemical differences between
the deposited films produced under different power and flow rate conditions. ToF
SIMS analysis demonstrated differing amounts of C5H5O (81 m/z) and C10H9O2 (161
m/z) species in the coatings which are related to the furan ring structure.
Through judicious choice of plasma polymerization parameters, the quantity of the
particle aggregates was reduced, and the fabricated plasma polymer coatings were
chemically uniform and smooth. Primary human fibroblasts were cultured on FMA
plasma polymer surfaces to determine the effect of surface chemical composition
and the presence of particle aggregates on cell culture. Particle aggregates were
shown to inhibit fibroblast attachment and proliferation.
PMID- 27609096
TI - Paeoniflorin Potentiates the Inhibitory Effects of Erlotinib in Pancreatic Cancer
Cell Lines by Reducing ErbB3 Phosphorylation.
AB - Blockade of the epidermal growth factor receptor (EGFR) by EGFR tyrosine kinase
inhibitors is insufficient for effective anti-tumor activity because the
reactivation of the ErbB3 signaling pathway significantly contributes to
activating the consequent phosphoinositide 3-kinase (PI3K)/Akt signaling pathway.
Combinatorial therapies including ErbB3 targeting may ameliorate tumor responses
to anti-EGFR therapies. In the present study, we found that in BxPC-3 and L3.6pl
cells, which highly expressed the ErbB3 receptor, significant reduction in cell
viability, induction of apoptosis were observed when treated with a combination
of erlotinib and PF compared to either agent alone. Moreover, in ErbB3-expressing
BxPC-3, L3.6pl and S2VP10 cell lines, the inhibition of ErbB3/PI3K/Akt
phosphorylation were observed when treated with PF. Most strikingly, both
EGFR/MAPK/Erk and ErbB3/PI3K/Akt activitions were substantially suppressed when
treated with the combination of PF and erlotinib. However, in the ErbB3-deficient
cell line MIAPaCa-2, no such effects were observed with similar treatments. Most
importantly, these in vitro results were replicated in nude mouse transplanted
tumor models. Taken together, our findings show that PF enhances the effect of
erlotinib in ErbB3-expressing pancreatic cancer cells by directly suppressing
ErbB3 activation, and PF in combination with erlotinib is much more effective as
an antitumor agent compared with either agent alone.
PMID- 27609098
TI - A literature review of flavonoids and lifespan in model organisms.
AB - Epidemiological data on consumption of flavonoid-containing food points to the
notion that some of these secondary plant metabolites may favour healthy ageing.
The aim of the present paper was to review the literature on lifespan extension
by flavonoids in worms, flies and mice. In most studies, worms and flies
experienced lifespan extension when supplemented with flavonoids either as
extracts or single compounds. Studies with mutant worms and flies give hints as
to which gene products may be regulated by flavonoids and consequently enhance
longevity. We discuss the data considering putative mechanisms that may underlie
flavonoid action such as energy-restriction-like effects, inhibition of insulin
like-growth-factor signalling, induction of antioxidant defence mechanisms,
hormesis as well as antimicrobial properties. However, it remains uncertain
whether human lifespan could be prolonged by increased flavonoid intake.
PMID- 27609099
TI - From heart failure to transplantation: genes, miRNAs, and biomarkers.
PMID- 27609100
TI - Professor Douglas Zipes MD.
PMID- 27609097
TI - Perception of risk and communication among conventional and complementary health
care providers involving cancer patients' use of complementary therapies: a
literature review.
AB - BACKGROUND: Communication between different health care providers (conventional
and complementary) and cancer patients about their use of complementary therapies
affects the health and safety of the patients. The aim of this study was to
examine the qualitative research literature on the perception of and
communication about the risk of complementary therapies between different health
care providers and cancer patients. METHODS: Systematic searches in six medical
databases covering literature from 2000 to 2015 were performed. The studies were
accessed according to the level of evidence and summarized into different risk
situations. Qualitative content analysis was used to analyze the text data, and
the codes were defined before and during the data analysis. RESULTS: Twenty-nine
papers were included in the primary analysis and five main themes were identified
and discussed. The main risk situations identified were 1. Differences in
treatment concepts and philosophical values among complementary and conventional
health care providers. 2. Adverse effects from complementary products and herbs
due to their contamination/toxicity and interactions with conventional cancer
treatment. 3. Health care physicians and oncologists find it difficult to
recommend many complementary modalities due to the lack of scientific evidence
for their effect. 4. Lack of knowledge and information about complementary and
conventional cancer treatments among different health care providers. CONCLUSION:
The risk of consuming herbs and products containing high level of toxins is a
considerable threat to patient safety (direct risk). At the same time, the lack
of scientific evidence of effect for many complementary therapies and differences
in treatment philosophy among complementary and conventional health care
providers potentially hinder effective communication about these threats with
mutual patients (indirect risk). As such, indirect risk may pose an additional
risk to patients who want to combine complementary therapies with conventional
treatment in cancer care. Health care providers who care for cancer patients
should be aware of these risks.
PMID- 27609102
TI - Professor Ben Freedman OAM.
PMID- 27609101
TI - The Victor Chang cardiac research institute.
PMID- 27609103
TI - The Acute Heart Failure Academy.
PMID- 27609104
TI - Re: Angina pectoris revisited; exertional angina preceded Martin Luther's last
stretch of a final journey; European Heart Journal (2016) 37, 206-216.
PMID- 27609105
TI - Robust Assessment of Molecular Size Distribution of Meningococcal AC Vaccine.
AB - The molecular size of meningococcal polysaccharides is an important
physicochemical parameter that is related to immunogenicity and efficacy. A
simple method for size-exclusion chromatography was developed, optimized, and
applied for safe and rapid fractionation of meningococcal polysaccharide AC
vaccine. Pooling of the fractions collected from size-exclusion chromatography
was investigated and evaluated, rather than analyzing each fraction separately,
for determining the percentages of meningococcal polysaccharide A and C that were
eluted before the distribution coefficient of 0.5. Pooling is preferred rather
than analyzing each fraction individually, as it is easily handled, faster,
simpler, less expensive, more accurate, safe, and applicable. The developed
method was validated and successfully applied for the determination of
meningococcal polysaccharide vaccine serotype A and C in quality-control and
commercial samples.
PMID- 27609107
TI - Auxin-cytokinin interaction and variations in their metabolic products in the
regulation of organogenesis in two Eucomis species.
AB - In the current study, we evaluated the effect of alpha-naphthaleneacetic acid
(NAA) individually or in combination with different cytokinins (CKs) including
benzyladenine (BA), meta-topolin (mT) and isopentenyladenine (iP) on
organogenesis, auxin and CK content in Eucomis autumnalis subspecies autumnalis
(EA) and Eucomis zambesiaca (EZ). These species were used as model plants due to
their ornamental and medicinal properties. Three leaf explants were inoculated in
screw-cap jars containing 30mL Murashige and Skoog (MS) media supplemented with
5MUM NAA alone or in combination with 5MUM CK (BA, mT or iP). After 10 weeks (EA)
or 15 weeks (EZ), parameters including shoot and root growth as well as plant
fresh weight were recorded. For analysis of auxin and CK content, whole plantlets
were harvested, pooled and freeze-dried for the different treatments. In both
species, shoot and root proliferation as well as plant biomass were generally
higher when NAA was combined with the individual CK than in NAA or CK treatment.
The highest concentration of indole-3-acetic acid (IAA, 619pmolg-1 DW) and 2
oxindole-3-acetic acid (OxIAA, 2381pmolg-1 DW) were observed in EA-treated with
NAA alone while mT treatment (without NAA) had the most abundant indole-3-acetyl
l-aspartic acid (IAAsp, 904 and 582pmolg-1 DW for EA and EZ, respectively) in
both species. A significant concentration of total endogenous CK accumulated in
both Eucomis regenerants from mT and mT+NAA when compared to the other
treatments. The majority of the detected CKs were of the aromatic CK-type, mainly
free bases. The potential physiological roles of these quantified phytohormones
in relation to the observed morphological responses are discussed.
PMID- 27609106
TI - Advanced Glycation End Products Predict Loss of Renal Function and Correlate With
Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.
AB - We examined associations of advanced glycation end products (AGEs) with renal
function loss (RFL) and its structural determinants in American Indians with type
2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective
efficacy of losartan. Participants remained under observation after the trial
concluded. Glomerular filtration rate (GFR) was measured annually. Kidney
biopsies were performed at the end of the trial. Five AGEs were measured in serum
collected at enrollment and at kidney biopsy. RFL was defined as >=40% decline of
measured GFR from baseline. Of 168 participants (mean baseline age 41 years,
HbA1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached
the RFL end point during median follow-up of 8.0 years. After multivariable
adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI
1.08-2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65])
concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine,
and methylglyoxal hydroimidazolone correlated positively with cortical
interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P =
0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone
and methylglyoxal hydroimidazolone correlated negatively with total filtration
surface per glomerulus (partial r = -0.26, P = 0.01; and partial r = -0.21, P =
0.046, respectively). AGEs improve prediction of RFL and its major structural
correlates.
PMID- 27609108
TI - Prevalence and incidence of chronic wounds and related complications: a protocol
for a systematic review.
AB - BACKGROUND: Chronic wounds impose a significant and often underappreciated burden
to the individual, the healthcare system and the society as a whole. Preliminary
literature search suggests that there are at present no reliable estimates on the
total prevalence of chronic wounds for different settings and categories of
chronic wounds. Such information is essential for policy and planning purposes as
the increasing number of elderly and the prevalence of lifestyle diseases point
in the direction of an increased burden. Knowledge about the prevalence and
incidence of chronic wounds in relation to population characteristics is
important for informing healthcare planning and resource allocation. The
objective is to present a transparent process for how to review the existing
literature on the prevalence and incidence rates of chronic wounds and resulting
implications. METHODS/DESIGN: We will search electronic bibliographic databases
(MEDLINE, EMBASE, the EBM Reviews and Cochrane, Cumulative Index to Nursing and
allied Health Literature (CINAHL), PsycINFO, Global Health) and reference lists
of included articles. Two investigators will independently screen titles and
abstracts and select studies involving adults with chronic wounds. These
investigators will also independently extract data using a pre-designed data
extraction form that will cover information on demographics, diagnostics
including disease prevalence, medical history, hospital and community-based
management and outcomes. Subgroup analysis and sensitivity analysis will be
performed to address the heterogeneity across studies. Meta-analysis will also be
performed if homogeneous group of studies will be found. The collective evidence
will be further stratified according to the important background variables if
allowed. DISCUSSION: This study will describe the available epidemiological
evidence and summarise prevalence and incidence rates of chronic wounds and
related complications. A better understanding of the relationship between
population profile and the prevalence of chronic wounds and related complications
will be helpful in the development of guidelines for patient management.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037355.
PMID- 27609110
TI - The impact of radiotherapy on clinical outcomes in parameningeal
rhabdomyosarcoma.
AB - PURPOSE: Radiotherapy (RT) is considered a mainstay of treatment in parameningeal
rhabdomyosarcoma (PM-RMS). We aim to determine the treatment outcomes and
prognostic factors for PM-RMS patients who treated with RT. In addition, we tried
to evaluate the adequate dose and timing of RT. MATERIALS AND METHODS: Twenty-two
patients with PM-RMS from 1995 to 2013 were evaluated. Seven patients had
intracranial extension (ICE) and 17 patients had skull base bony erosion (SBBE).
Five patients showed distant metastases at the time of diagnosis. All patients
underwent chemotherapy and RT. The median radiation dose was 50.4 Gy (range, 40.0
to 56.0 Gy). RESULTS: The median follow-up was 28.7 months. Twelve patients
(54.5%) experienced failure after treatment; 4 local, 2 regional, and 6 distant
failures. The 5-year local control (LC) and overall survival (OS) were 77.7% and
38.5%, respectively. The 5-year OS rate was 50.8% for patients without distant
metastases and 0% for patients with metastases (p < 0.001). Radiation dose (<50
Gy vs. >=50 Gy) did not compromise the LC (p = 0.645). However, LC was affected
by ICE (p = 0.031). Delayed administration (>22 weeks) of RT was related to a
higher rate of local failure (40.0%). CONCLUSION: RT resulted in a higher rate of
local control in PM-RMS. However, it was not extended to survival outcome. A more
effective treatment for PM-RMS is warranted.
PMID- 27609109
TI - Immunomodulatory effect of captopril and local irradiation on myeloid-derived
suppressor cells.
AB - PURPOSE: This study is to investigate the effect of captopril when combined with
irradiation. MATERIALS AND METHODS: 4T1 (mouse mammary carcinoma) cells were
injected in the right hind leg of Balb/c mice. Mice were randomized to four
groups; control (group 1), captopril-treated (group 2), irradiated (group 3),
irradiated and captopril-treated concurrently (group 4). Captopril was
administered by intraperitoneal injection (10 mg/kg) daily and irradiation was
delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of
splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated
neutrophils [TANs]) were assessed using flow cytometry and expression of vascular
endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha (HIF
1alpha) of tumor was evaluated by immunohistochemical (IHC) staining. RESULTS:
The mean tumor volumes (+/-standard error) at the 15th day after randomization
were 1,382.0 (+/-201.2) mm3 (group 1), 559.9 (+/-67.8) mm3 (group 3), and 370.5
(+/- 48.1) mm3 (group 4), respectively. For G-MDSCs, irradiation reversed
decreased expression of CD101 from tumor-bearing mice, and additional increase of
CD101 expression was induced by captopril administration. Similar tendency was
observed in TANs. The expression of tumor-necrosis factor-associated molecules,
CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further
increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF
and HIF-1alpha positivity in tumor cells were decreased when treated with
captopril. CONCLUSION: Captopril is suggested to have additional effect when
combined to irradiation in a murine tumor model by modulation of MDSCs and
angiogenesis.
PMID- 27609112
TI - Strain mapping in a nanoscale-triangular SiGe pattern by dark-field electron
holography with medium magnification mode.
AB - Recent years have seen a great deal of progress in the development of
transmission electron microscopy-based techniques for strain measurement. Dark
field electron holography (DFEH) is a new technique offering configuration of the
off-axis principle. Using this technique with medium magnification (Holo-M), we
carried out strain measurements in nanoscale-triangular SiGe/(001) Si with (004),
(2-20) and (-111) diffraction spots. The reconstruction of holograms and
interpretation of strain maps in term of strain precision were discussed and the
strain distributions in the SiGe/(001) Si patterns were visualized. Based on
linear anisotropic elastic theory for strain simulation, the simulated results
obtained by the finite element method compared with the experimental results
acquired by DFEH. The strain values were found to be 0.9-1.0%, 1.1-1.2% and 1.0
1.1%, for the (004), (2-20) and (-111) diffracted beams, respectively, and the
strain precisions were determined to be ~2.1 * 10-3, 3.2 * 10-3 and 9.1 * 10-3
for the corresponding diffraction spots. As a result, DFEH is highlighted as a
powerful technique for strain measurement, offering high-strain precision, high
spatial resolution and a large field of view.
PMID- 27609111
TI - Calcium/calmodulin alleviates substrate inhibition in a strawberry UDP
glucosyltransferase involved in fruit anthocyanin biosynthesis.
AB - BACKGROUND: UDP-glucosyltransferase (UGT) is a key enzyme for anthocyanin
biosynthesis, which by catalyzing glycosylation of anthocyanidins increases their
solubility and accumulation in plants. Previously we showed that pre-harvest
spray of CaCl2 enhanced anthocyanin accumulation in strawberry fruit by
stimulating the expression of anthocyanin structural genes including a fruit
specific FvUGT1. RESULTS: To further understand the regulation of anthocyanin
biosynthesis, we conducted kinetic analysis of recombinant FvUGT1 on
glycosylation of pelargonidin, the major anthocyanidin in strawberry fruit. At
the fixed pelargonidin concentration, FvUGT1 catalyzed the sugar transfer from
UDP-glucose basically following Michaelis-Menten kinetics. By contrast, at the
fixed UDP-glucose concentration, pelargonidin over 150 MUM exhibited marked
partial substrate inhibition in an uncompetitive mode. These results suggest that
the sugar acceptor at high concentration inhibits FvUGT1 activity by binding to
another site in addition to the catalytic site. Furthermore, calcium/calmodulin
specifically bound FvUGT1 at a site partially overlapping with the interdomain
linker, and significantly relieved the substrate inhibition. In the presence of
0.1 and 0.5 MUM calmodulin, V max was increased by 71.4 and 327 %, respectively.
CONCLUSIONS: FvUGT1 activity is inhibited by anthocyanidin, the sugar acceptor
substrate, and calcium/calmodulin binding to FvUGT1 enhances anthocyanin
accumulation via alleviation of this substrate inhibition.
PMID- 27609113
TI - Cefazolin pharmacokinetics in cats under surgical conditions.
AB - Objectives The aim of this study was to determine the plasma pharmacokinetic
profile, tissue concentrations and urine elimination of cefazolin in cats under
surgical conditions after a single intravenous dose of 20 mg/kg. Methods
Intravenous cefazolin (20 mg/kg) was administered to nine young mixed-breed cats
30 mins before they underwent surgical procedures (ovariectomy or orchiectomy).
After antibiotic administration, samples from blood, some tissues and urine were
taken. Cefazolin concentrations were determined in all biological matrices and
pharmacokinetic parameters were estimated. Results Initial plasma concentrations
were high (Cp(0), 134.80 +/- 40.54 ug/ml), with fast and moderately wide
distribution (distribution half-life [t1/2(d)] 0.16 +/- 0.15 h; volume of
distribution at steady state [V(d[ss])] 0.29 +/- 0.10 l/kg) and rapid elimination
(body clearance [ClB], 0.21 +/- 0.06 l/h/kg; elimination half-life [t1/2], 1.18
+/- 0.27 h; mean residence time 1.42 +/- 0.36 h). Thirty to 60 mins after
intravenous administration, cefazolin tissue concentrations ranged from 9.24
ug/ml (subcutaneous tissue) to 26.44 ug/ml (ovary). The tissue/plasma
concentration ratio ranged from 0.18 (muscle) to 0.58 (ovary). Cefazolin urine
concentrations were high with 84.2% of the administered dose being eliminated in
the first 6 h postadministration. Conclusions and relevance Cefazolin plasma
concentrations remained above a minimum inhibitory concentration of ?2 ug/ml up
to 4 h in all the studied cats. This suggests that a single intravenous dose of
20 mg/kg cefazolin would be adequate for perioperative prophylactic use in cats.
PMID- 27609114
TI - High prevalence of intracranial aneurysms in patients with aortic dissection or
aneurysm: feasibility of extended aorta CT angiography with involvement of
intracranial arteries.
AB - INTRODUCTION: Previous studies have suggested a higher prevalence of intracranial
aneurysms (IAs) in patients with aortic aneurysms (AAs). OBJECTIVE: To carry out
a preliminary study to evaluate the prevalence of IAs in these patients and the
diagnostic feasibility of extended aorta CT angiography (CTA), including
intracranial arteries as well as the aorta. MATERIALS AND METHODS: We
retrospectively reviewed all patients with a clinical diagnosis of AA or aortic
dissection (AD) who had undergone aorta CTA as well as MR angiography, CTA,
and/or DSA of the brain between 2009 and 2014. Since 2012, the extended aorta CTA
protocol has been applied in these patients. Characteristics of IAs were
classified with baseline clinical data. For quantitative and qualitative
assessment by two independent raters, brain images obtained by extended aorta CTA
and brain CTA were compared. The radiation dose of the two aorta protocols was
compared. RESULTS: The prevalence of IA was 22.2% (35/158). All IAs were detected
by extended aorta CTA, except one small aneurysm (<3 mm). The mean vascular
attenuation value between brain images showed no difference (p=0.83), but the
contrast-to-noise ratio was significantly lower in extended aorta CTA (p<0.001).
In qualitative assessment, the interobserver agreement was substantial (k=0.79).
For the radiation dose, the dose-length product of the extended aorta CTA
increased with increment of the scan range (p=0.048). CONCLUSIONS: With a high
prevalence of IAs in patients with ADs or AAs, extended aorta CTA could be used
to evaluate aorta disease and IA in a single session. However, further
prospective studies are needed to prove efficacy and safety of the extended aorta
CTA protocol in patients with AAs or ADs.
PMID- 27609115
TI - Differences in sex distribution, anatomic location and MR imaging appearance of
pediatric compared to adult chordomas.
AB - BACKGROUND: Chordomas are rare malignancies that primarily affect adults, but
also rarely affect pediatric patients. We compared the imaging appearance,
demographic and anatomic distributions of adult and pediatric chordomas in a
large cohort. METHODS: We performed a retrospective review of medical records of
220 subjects with histologically confirmed chordomas of the axial skeleton and
pre-treatment magnetic resonance imaging studies. Age, sex, type of chordoma
(conventional, chondroid or dedifferentiated), the anatomic location of the
chordoma, as well as whether the lesion was primarily extra-osseous were
recorded. Pediatric subjects were less than 21 years at the time of diagnosis.
Binomial two-sample tests of proportions and Fisher's exact tests were used to
compare proportions between the pediatric and adult subjects. RESULTS: Fifty six
pediatric subjects (58.9 % female) and 164 adult subjects (42.1 % female) were
identified. The proportion of female subjects with chordomas was significantly
higher in the pediatric cohort compared to the adult cohort (P = 0.04). Most
chordomas occur in Caucasians, however African-Americans were more represented in
the pediatric cohort than in the adult cohort (P = 0.01). 69.6 % (39/56) of the
pediatric chordomas involved the clivus/skull base and cervical spine compared to
29.3 % (48/164) of the adult chordomas (P = 1.99 * 10(-7)). Only 1.8 % (1/56) of
the pediatric chordomas was in the sacrococcygeal region compared to 36.0 %
(59/164) of the adult chordomas (P = 2.55 * 10(-8)). In cases where pre-treatment
imaging was available, 93.8 % (16/17) of pediatric chordomas were predominantly
extra-osseous compared to 76.7 % (46/60) of adult chordomas (P = 0.17).
CONCLUSIONS: Pediatric chordomas more often affect females and occur most
frequently at the craniocervical junction with decrease in incidence distally in
the spine, whereas adult chordomas most frequently involve the craniocervical and
sacrococcygeal regions.
PMID- 27609116
TI - Localization of a red fluorescence protein adsorbed on wild type and mutant
spores of Bacillus subtilis.
AB - BACKGROUND: Bacterial spores have been proposed as vehicles to display
heterologous proteins for the development of mucosal vaccines, biocatalysts,
bioremediation and diagnostic tools. Two approaches have been developed to
display proteins on the spore surface: a recombinant approach, based on the
construction of gene fusions between DNA molecules coding for a spore surface
protein (carrier) and for the heterologous protein to be displayed (passenger);
and a non-recombinant approach based on spore adsorption, a spontaneous
interaction between negatively charged, hydrophobic spores and purified proteins.
The molecular details of spore adsorption have not been fully clarified yet.
RESULTS: We used the monomeric Red Fluorescent Protein (mRFP) of the coral
Discosoma sp. and Bacillus subtilis spores of a wild type and an isogenic mutant
strain lacking the CotH protein to clarify the adsorption process. Mutant spores,
characterized by a strongly altered coat, were more efficient than wild type
spores in adsorbing mRFP but the interaction was less stable and mRFP could be in
part released by raising the pH of the spore suspension. A collection of isogenic
strains carrying GFP fused to proteins restricted in different compartments of
the B. subtilis spore was used to localize adsorbed mRFP molecules. In wild type
spores mRFP infiltrated through crust and outer coat, localized in the inner coat
and was not surface exposed. In mutant spores mRFP was present in all surface
layers, inner, outer coat and crust and was exposed on the spore surface.
CONCLUSIONS: Our results indicate that different spores can be selected for
different applications. Wild type spores are preferable when a very tight protein
spore interaction is needed, for example to develop reusable biocatalysts or
bioremediation systems for field applications. cotH mutant spores are instead
preferable when the heterologous protein has to be displayed on the spore surface
or has to be released, as could be the case in mucosal delivery systems for
antigens and drugs, respectively.
PMID- 27609118
TI - Matching genes with constitution and environment.
PMID- 27609117
TI - The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress
markers in cerebral ischemia.
AB - Antioxidants, with reported neuroprotective activity, encounter free radical
induced neural damage leading to reduced risk of cerebral ischemia-reperfusion
(IR) injury. Safranal, an antioxidant drug with potential role in the
amelioration of cerebral ischemia, endures low solubility and poor absorption
property thus resulting a low serum and tissue bioavailability. This research
aims to prepare nanoemulsion with the concept; to increase the bioavailability in
order to reduce oxidative stress-induced brain injury as well as to evaluate the
brain-drug targeting following non-invasive nasal route administration in middle
cerebral artery occlusion (MCAO) animal model. Titration method was used to
prepare safranal mucoadhesive nanoemulsion (SMNE) followed by further
characterization, i.e. entrapment efficiency, particles size, and zeta potential
study. Optimized SMNE showed; mean globule size of 89.64 nm (+/-9.12), zeta
potential -11.39 mV (+/-1.32), drug content 98.47% (+/-1.01), and viscosity of
124 cp (+/-14). Rats were subjected to 2 h of MCAO, successively followed by a 22
h reperfusion, after which the grip strength, locomotor activity, and biochemical
studies, i.e. glutathione reductase (GR), glutathione peroxidase, lipid
peroxidation, catalase, and superoxide dismutase were studied as assessment tool
for effective treatment in brain. SMNE administered i.n. (intranasal) in MCAO
induced cerebral ischemia rats exhibited significant improvement in
neurobehavioral (locomotor and grip strength) and antioxidant activity as well as
histopathological studies. The toxicity studies performed at the end revealed
safe nature of developed SMNE.
PMID- 27609119
TI - Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with
Rheumatoid Arthritis via Induced Pluripotent Stem Cells.
AB - Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis
(RA) patients. This study aimed to generate and characterise cardiomyocytes from
induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like
synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were
successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The
pluripotency of iPSCs was confirmed by quantitative reverse transcription
polymerase chain reaction and immunofluorescence staining. Established iPSCs were
differentiated into cardiomyocytes using a small molecule-based monolayer
differentiation protocol. Within 12 days of cardiac differentiation from patient
specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were
observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with
antibodies against cardiac markers and similar expression profiles of cardiac
specific genes. Intracellular calcium signalling was recorded to compare calcium
handling properties among cardiomyocytes differentiated from the three groups of
iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium
transients than the control groups. Peak tangential stress and the maximum
contractile rate were also decreased in RA-iPSC-CMs, suggesting that
contractility was reduced. This study demonstrates the successful generation of
functional cardiomyocytes from pathogenic synovial cells in RA patients through
iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to
investigate the pathophysiology of cardiac involvement in RA.
PMID- 27609120
TI - Determination of the chest wall thicknesses and needle thoracostomy success rates
at second and fifth intercostal spaces: a cadaver-based study.
AB - INTRODUCTION: The purposes of this study were to measure the chest wall
thicknesses (CWTs) at second intercostal space (ICS) mid-clavicular line (MCL)
and fifth ICS MAL directly, and compare the actual success rates of needle
thoracostomies (NTs) by inserting a 5-cm-long syringe needle. Predictive values
of weight, body mass index (BMI) and CWT were also analyzed. MATERIALS AND
METHODS: This study included 199 measurements of 50 adult fresh cadavers from
both hemithoraces. Five-centimeter-long syringe needles were inserted and
secured. Penetration into the pleural cavity was assessed, and CWTs at 4
locations were measured. Achieved power of this study for the primary aim of CWT
comparison from 2nd and 5th ICSs was .94. RESULTS: Overall mean CWTs at 2nd ICS
MCL and 5th ICS MAL were measured as 2.46 +/- 0.78 and 2.89 +/- 1.09,
respectively, and 5th ICS MAL was found to be statistically thicker (P = .002).
The success rate of NT at 2nd ICS MCL was 87% (95% CI, 80-94), and that at 5th
ICS MAL was 78% (95% CI, 70-86; P = .3570). Only 6 (17.1%) of 35 failed NTs had a
CWT greater than 5-cm. Needle thoracostomy has failed in 29 (14.9%) of 194
locations, despite a CWT less than 5-cm. Below a weight of 72 kg, BMI of 23
kg/m2, or CWT of 2.4 cm, all NTs were successful. DISCUSSION AND CONCLUSIONS: In
this report, we present the largest cadaver-based cohort to date to the best of
our knowledge, and we observed a statistically nonsignificant 9% more NT success
rate at 2nd ICS at a power of 88% and statistically significant more success rate
in males at 5th ICS was (47.7%). We also observed thinner CWTs and higher success
rates than previous imaging-based studies. A BMI of 23 kg/m2 or less and weight
of 72 kg or less seem to accurately rule-out NT failure in cadavers, and they
seem to be better predictors at the bedside.
PMID- 27609122
TI - Prolonged hypocalcemia refractory to calcium gluconate after ammonium bifluoride
ingestion in a pediatric patient.
PMID- 27609121
TI - Evaluation of proadrenomedullin as a diagnostic or prognostic biomarker of acute
appendicitis in children.
AB - INTRODUCTION: A delay in the diagnosis of acute appendicitis (AA), with the added
complication of symptoms that mimic other self-limited causes of abdominal pain,
can lead to an increase in ruptured appendices and morbimortality. None of the
serum biomarkers evaluated to date have shown a predictive value for early
diagnosis. OBJECTIVE: The objective of this study was to evaluate the usefulness
of proadrenomedullin (MR-proADM) in the diagnosis of AA in children presenting
with acute abdominal pain. METHODS: A single-center prospective observational
study was conducted in 136 children who presented to the emergency department
with suspected AA. RESULTS: Forty-four (32.5%) children had AA, and 9 (20.5%) had
perforated appendicitis. The mean concentration of MR-proADM was significantly
higher in children with AA than in children with nonspecific abdominal pain (NAP)
(0.54 nmol/L; 95% confidence interval, 0.46-0.55 and 0.37 nmol/L; 95% confidence
interval, 0.35-0.40, respectively). Performance characteristics of MR-proADM
alone were not optimal. However, after combining best cutoff points, the
combination of a C-reactive protein level of <0.3 mg/dL and a MR-proADM level of
<0.34 nmol/L showed 100% sensitivity and negative predictive value, with 61%
specificity. CONCLUSIONS: Although MR-proADM values are higher in children with
AA than in children with nonspecific abdominal pain, these values do not help in
the early diagnosis of AA. The combination of low C-reactive protein and low MR
proADM levels is useful for the identification of children with a low risk of AA.
PMID- 27609124
TI - Exosomal proteome analysis of cerebrospinal fluid detects biosignatures of
neuromyelitis optica and multiple sclerosis.
AB - Quantitative proteomic analysis of exosomes isolated from cerebrospinal fluid
(CSF) of neuromyelitis optica (NMO) patients detected signature proteins
differentiating NMO from multiple sclerosis (MS) and idiopathic longitudinally
extensive transverse myelitis. Exosomes with good yields were obtained using
ultracentrifugation from pooled CSF assisted by chemokine-based clustering
strategy, which improved target molecule identification by providing amplified
fold change values. 442 significant proteins generated a list of signature
molecules of diseases validated primarily by the identification of known markers
such as glial fibrillary acidic protein (GFAP) and fibronectin specific to NMO
and MS respectively. MetaCore pathway analysis of significant proteins supported
the involvement of these proteins in disease progression via neurological
pathway. Expression levels of target molecules from orthogonal label-free
quantification employing quadrupole-Orbitrap hybrid mass spectrometry were in
good agreement with those from Western blotting. Additional investigation of GFAP
and fibronectin as representative disease molecules revealed their presence in
intact exosomes as detected by flow cytometry. This comprehensive study suggests
that the exosomal proteomic analysis of CSF can be applied to the identification
and characterization of inflammatory disorders of the central nervous system.
PMID- 27609123
TI - Genotyping of 19 red cell antigens, including RHD, using liquid bead arrays.
AB - BACKGROUND: Traditionally, the determination of blood group has been performed
using serological techniques. Due to the drawbacks of using antisera, molecular
typing of blood groups has been introduced. However, the commonly used genotyping
assays in blood banks have limitations because the panels for these were based on
genetic variations in Caucasians. METHODS: We developed a multiplex human
erythrocyte antigen genotyping assay using allele-specific primer extensions and
hybridization with bead microarrays. Single nucleotide polymorphisms (SNP) were
genotyped for the 18 red cell antigens and wild-type RHD, DEL, and complete
deletion were examined for RHD. The cut-off of median fluorescence intensity
(MFI) for each allele was optimized. In the evaluation stage, the results of 87
samples were compared with those from other genotyping methods, and 26 serologic
results were also compared. RESULTS: The cut-off values were determined using -1
and -2 standard deviation (SD) of the minimum adjusted MFI for SNP detection.
Complete deletion was determined with raw MFI+2SD. In comparison with the other
methods, the kappa values were 0.984 overall. Compared with serologic methods,
our assay showed discrepancy in 2 S/s, 3 C/c, and 3 Dia/Dib antigens.
CONCLUSIONS: Our method reliably predicts the presence or the absence of the 19
antigens.
PMID- 27609125
TI - The role of the ventro-lateral prefrontal cortex in idiom comprehension: An rTMS
study.
AB - Previous research is equivocal with respect to the neural substrates of idiom
processing. Particularly elusive is the role of the left ventro-lateral
prefrontal cortex (VLPFC), a region implicated in semantic control generally.
Although fMRI studies have shown that the left VLPFC is active during idiom
processing (see Rapp et al. (2012), for review), rTMS studies have failed to
corroborate a clear role of this prefrontal region (e.g., Oliveri et al., 2004).
We investigated this issue using a semantic meaningfulness judgment task that
compared idiom comprehension following rTMS-stimulation to the left VLPFC
relative to a control site (vertex). We also investigated whether individual
differences in general cognitive capacity among comprehenders modulated the
effects of rTMS. The results indicate that left VLPFC stimulation particularly
affected the processing of low-familiar idioms, possibly because these items
involve a maximal semantic conflict between a salient literal and less-known
figurative meaning. Of note, this pattern only emerged for comprehenders with
higher cognitive control capacity, possibly because they were more likely to
activate or maintain multiple semantic representations during idiom processing,
which required VLPFC integrity. Taken together, the results support the
importance of the left VLPFC to idiom processing.
PMID- 27609126
TI - Testing the importance of the Medial Temporal Lobes in human interoception: Does
it matter if there is a memory component to the task?
AB - Interoception is the ability to consciously perceive internal bodily states.
Neuroimaging suggests that the insula (IC) and anterior cingulate cortex (ACC)
mediate interoception, while studies involving patients/animals with brain
lesions suggest the medial temporal lobe (MTL) is particularly important. One
reason for these contrasting conclusions may lie in the types of interoceptive
task used by these different approaches. Some tasks probably require integration
of current physiological state with mnemonic information (e.g., how much one last
ate), and these may be especially reliant upon MTL processing. We compared one
task that probably requires integration - a water load task - with one that
likely does not - a heart-rate tracking task - in two individuals with selective
MTL damage (and with intact IC and ACC). A group of matched healthy individuals
served as controls. The main finding was that individuals with MTL damage,
relative to controls, were equally and significantly impaired on both types of
interoception task. This suggests that MTL structures are involved in mediating
interoception even when using a task (heart rate tracking) that does not
seemingly require memory and that in neuroimaging studies activates the IC and
ACC. The reasons for this apparent inconsistency with neuroimaging findings and
the functional role of the MTL in interoception are discussed.
PMID- 27609128
TI - Men and women should practise safe sex for six months to avoid Zika, says WHO.
PMID- 27609129
TI - Narrative and reflection: training in a correctional facility.
AB - This commentary describes the author's experience working at two separate
detention centres during her fellowship. She initially describes her experience
performing forensic evaluations. The terms 'competency to stand trial' and
'criminal responsibility' are defined. It then describes the author's experience
working in an inner city and suburban detention centre. The two environments and
patient demographics are compared to a traditional inpatient or outpatient
community setting. Fictional patient encounters, based on an amalgamation of
actual patients, are discussed.
PMID- 27609127
TI - Hemispheric differences and similarities in comprehending more and less
predictable sentences.
AB - With a growing literature demonstrating the predictive nature of language
processing, the current study examines contributions of the brain's two
hemispheres in processing more and less probable sentence continuations.
Specifically, we use the ERP method in conjunction with the visual half-field
paradigm to test for hemispheric utilization of sentential constraint to (pre
)activate lexical information and resolve meaning. Taking advantage of the N400's
semantic sensitivities, we find support for both hemispheres exhibiting
remarkably similar involvement, across a range of message level constraint, in
meaning construction. In contrast, hemispheric ERP patterns at a later processing
stage differed, as reflected in an anterior post-N400 positivity (PNP) to
constraint violations for words presented to the right but not left visual field
(indicating a left hemisphere processing bias). We show here that hemispheric
involvement in predictive sentence comprehension varies at different stages of
word processing, and we examine these patterns' (in)consistencies with findings
from the hemi-field and central visual presentation literature.
PMID- 27609132
TI - People with MS should consume a low-salt diet - Commentary.
PMID- 27609133
TI - People with MS should consume a low-salt diet - NO.
PMID- 27609131
TI - Predicting the synergy of multiple stress effects.
AB - Toxicants and other, non-chemical environmental stressors contribute to the
global biodiversity crisis. Examples include the loss of bees and the reduction
of aquatic biodiversity. Although non-compliance with regulations might be
contributing, the widespread existence of these impacts suggests that for example
the current approach of pesticide risk assessment fails to protect biodiversity
when multiple stressors concurrently affect organisms. To quantify such multiple
stress effects, we analysed all applicable aquatic studies and found that the
presence of environmental stressors increases individual sensitivity to toxicants
(pesticides, trace metals) by a factor of up to 100. To predict this dependence,
we developed the "Stress Addition Model" (SAM). With the SAM, we assume that each
individual has a general stress capacity towards all types of specific stress
that should not be exhausted. Experimental stress levels are transferred into
general stress levels of the SAM using the stress-related mortality as a common
link. These general stress levels of independent stressors are additive, with the
sum determining the total stress exerted on a population. With this approach, we
provide a tool that quantitatively predicts the highly synergistic direct effects
of independent stressor combinations.
PMID- 27609130
TI - A 10-year cohort analysis of routine paediatric ART data in a rural South African
setting.
AB - South Africa's paediatric antiretroviral therapy (ART) programme is managed using
a monitoring and evaluation tool known as TIER.Net. This electronic system has
several advantages over paper-based systems, allowing profiling of the paediatric
ART programme over time. We analysed anonymized TIER.Net data for HIV-infected
children aged <15 years who had initiated ART in a rural district of South Africa
between 2005 and 2014. We performed Kaplan-Meier survival analysis to assess
outcomes over time. Records of 5461 children were available for analysis; 3593
(66%) children were retained in care. Losses from the programme were higher in
children initiated on treatment in more recent years (P < 0.0001) and in children
aged <=1 year at treatment initiation (P < 0.0001). For children aged <3 years,
abacavir was associated with a significantly higher rate of loss from the
programme compared to stavudine (hazard ratio 1.9, P < 0.001). Viral load was
suppressed in 48-52% of the cohort, with no significant change over the years (P
= 0.398). Analysis of TIER.Net data over time provides enhanced insights into the
performance of the paediatric ART programme and highlights interventions to
improve programme performance.
PMID- 27609134
TI - People with MS should consume a low-salt diet - YES.
PMID- 27609135
TI - Response to "An Alternative Method of Breast Implant Insertion".
PMID- 27609136
TI - An Alternative Method of Breast Implant Insertion.
PMID- 27609137
TI - A detailed spatial analysis on contrasting cancer incidence patterns in thyroid
and lung cancer in Toronto women.
AB - BACKGROUND: Thyroid cancer has been rapidly rising in incidence in Canada;
however, in contrast, lung cancer appears to be decreasing in incidence in
Canadian men and stable in women. Moreover, disease-related mortality risk is
generally very low in TC but high in LC. We performed a geographic spatial
analysis in metropolitan Toronto, Canada to determine if there is regional
variability of respective risks of thyroid cancer (TC) and lung cancer (LC),
among women. Women were of particular interest for this study, given their known
predilection for thyroid cancer. METHODS: The postal codes of all females with TC
or LC, residing in metropolitan Toronto from 2004 to 2008, were geocoded to point
locations according to 2006 Canadian Census data. The data were analysed using a
log-Gaussian Cox Process, where the intensity of age-adjusted cancer cases was
modelled as a log-linear combination of the population at risk, explanatory
variables (race, immigration, and median household income), and a residual
spatially varying random effect. For each respective malignancy, statistical
models were fit to make quantify the relationship between cancer incidence and
explanatory variables. RESULTS: We included 2230 women with TC and 2412 with LC.
The distribution of TC and LC cases contrasted inversely among Toronto
neighbourhoods with the highest TC incidence in the Northeast and the highest LC
incidence in the Southeast. A higher proportion of Asian ethnicity was associated
with higher regional risk of TC and lower risk of LC. A higher proportion of
recent immigrants was associated with increased LC and lower TC risk, whereas
median household income and proportions of African ethnicity were not
significantly associated with risk of either cancer, after adjustment for other
socio-demographic variables. CONCLUSIONS: We observed contrasting regional
distributions of female TC and LC cases in Toronto. The differences were partly
attributed to ethnic composition variability and the proportion of recent
immigrants, but substantial unexplained residual variation of incidence patterns
of these malignancies exists, suggesting that more individual-level research is
needed to explain the regional variability of incidence of these malignancies.
PMID- 27609138
TI - Casting a wider net in behavioral health screening in primary care: a preliminary
study of the Outcome Rating Scale.
AB - : Introduction The integration of behavioral health services into primary care
has led to enhanced use of brief screening measures to identify mental health
problems. Although useful, such instruments are largely symptom based and
diagnosis specific. This narrow focus can potentially limit the identification of
broader social or relational distress in patients that affect medical outcomes,
as well as present feasibility challenges using a multi-measure approach in
identifying mental health comorbidities. METHOD: This exploratory study of adult
primary care patients compared an ultra-brief, and widely used measure of global
distress across life functioning, the Outcome Rating Scale (ORS), with the
Patient Health Questionnaire (PHQ-9 and PHQ-2). RESULTS: Correlations between the
ORS and the PHQ-9 and PHQ-2 indicated agreement between the measures in
classifying patients, and the ORS identified significantly more patients in the
clinical range. Discussion Although results are preliminary, the ORS may cast a
wider net in identifying patients with significant distress in primary care.
PMID- 27609140
TI - The role of aquaporin-5 in cancer cell migration: A potential active participant.
AB - Emerging data identifies the water channel aquaporin-5 as a major player in
multiple cancers. Over-expression of aquaporin-5 has been associated with
increased metastasis and poor prognosis, suggesting that aquaporin-5 may enhance
cancer cell migration. This review aims to highlight the current knowledge and
hypothesis regarding downstream signaling partners of aquaporin-5 in relation to
cancer cell migration. The molecular mechanisms that link aquaporin-5 to cell
migration are not completely understood. Aquaporin-5 may promote cell movement by
increasing water uptake into the front of the cell allowing local swelling.
Aquaporin-5 may also activate extracellular-regulated kinases, increasing
proliferation and potentially stimulating the migration machinery. Thus, further
studies are warranted to identify the underlying mechanisms and signaling
pathways. This will reveal whether aquaporin-5 and downstream effectors could be
targets for developing new cancer therapeutics.
PMID- 27609139
TI - Differential timing of granule cell production during cerebellum development
underlies generation of the foliation pattern.
AB - BACKGROUND: The mouse cerebellum (Cb) has a remarkably complex foliated three
dimensional (3D) structure, but a stereotypical cytoarchitecture and local
circuitry. Little is known of the cellular behaviors and genes that function
during development to determine the foliation pattern. In the anteroposterior
axis the mammalian cerebellum is divided by lobules with distinct sizes, and the
foliation pattern differs along the mediolateral axis defining a medial vermis
and two lateral hemispheres. In the vermis, lobules are further grouped into four
anteroposterior zones (anterior, central, posterior and nodular zones) based on
genetic criteria, and each has distinct lobules. Since each cerebellar afferent
group projects to particular lobules and zones, it is critical to understand how
the 3D structure of the Cb is acquired. During cerebellar development, the
production of granule cells (gcs), the most numerous cell type in the brain, is
required for foliation. We hypothesized that the timing of gc accumulation is
different in the four vermal zones during development and contributes to the
distinct lobule morphologies. METHODS AND RESULTS: In order to test this idea, we
used genetic inducible fate mapping to quantify accumulation of gcs in each
lobule during the first two postnatal weeks in mice. The timing of gc production
was found to be particular to each lobule, and delayed in the central zone
lobules relative to the other zones. Quantification of gc proliferation and
differentiation at three time-points in lobules representing different zones,
revealed the delay involves a later onset of maximum differentiation and
prolonged proliferation of gc progenitors in the central zone. Similar
experiments in Engrailed mutants (En1 (-/+) ;En2 (-/-) ), which have a smaller Cb
and altered foliation pattern preferentially outside the central zone, showed
that gc production, proliferation and differentiation are altered such that the
differences between zones are attenuated compared to wild-type mice. CONCLUSIONS:
Our results reveal that gc production is differentially regulated in each zone of
the cerebellar vermis, and our mutant analysis indicates that the dynamics of gc
production plays a role in determining the 3D structure of the Cb.
PMID- 27609143
TI - Persistent occiput posterior position associated to asynclitism, solved by manual
rotation: is always possible to perform safely this maneuver?
PMID- 27609142
TI - Cloning and heterologous expression of a novel subgroup of class IV
polyhydroxyalkanoate synthase genes from the genus Bacillus.
AB - Many microorganisms harbor genes necessary to synthesize biodegradable plastics
known as polyhydroxyalkanoates (PHAs). We surveyed a genomic database and
discovered a new cluster of class IV PHA synthase genes (phaRC). These genes are
different in sequence and operon structure from any previously reported PHA
synthase. The newly discovered PhaRC synthase was demonstrated to produce PHAs in
recombinant Escherichia coli.
PMID- 27609141
TI - Copper oxide nanoparticle toxicity profiling using untargeted metabolomics.
AB - BACKGROUND: The rapidly increasing number of engineered nanoparticles (NPs), and
products containing NPs, raises concerns for human exposure and safety. With this
increasing, and ever changing, catalogue of NPs it is becoming more difficult to
adequately assess the toxic potential of new materials in a timely fashion. It is
therefore important to develop methods which can provide high-throughput
screening of biological responses. The use of omics technologies, including
metabolomics, can play a vital role in this process by providing relatively fast,
comprehensive, and cost-effective assessment of cellular responses. These
techniques thus provide the opportunity to identify specific toxicity pathways
and to generate hypotheses on how to reduce or abolish toxicity. RESULTS: We have
used untargeted metabolome analysis to determine differentially expressed
metabolites in human lung epithelial cells (A549) exposed to copper oxide
nanoparticles (CuO NPs). Toxicity hypotheses were then generated based on the
affected pathways, and critically tested using more conventional biochemical and
cellular assays. CuO NPs induced regulation of metabolites involved in oxidative
stress, hypertonic stress, and apoptosis. The involvement of oxidative stress was
clarified more easily than apoptosis, which involved control experiments to
confirm specific metabolites that could be used as standard markers for
apoptosis; based on this we tentatively propose methylnicotinamide as a generic
metabolic marker for apoptosis. CONCLUSIONS: Our findings are well aligned with
the current literature on CuO NP toxicity. We thus believe that untargeted
metabolomics profiling is a suitable tool for NP toxicity screening and
hypothesis generation.
PMID- 27609144
TI - Functional hearing in the classroom: assistive listening devices for students
with hearing impairment in a mainstream school setting.
AB - OBJECTIVE: To assess the benefit of assistive listening devices (ALDs) for
students with hearing impairment in mainstream schools. DESIGN: Speech
recognition (CNC words) in background noise was assessed in a typical classroom.
Participants underwent testing using four device configurations: (1) HA(s)/CI(s)
alone, (2) soundfield amplification, (3) remote microphone (Roger Pen) on desk
and (4) remote microphone at the loudspeaker. A sub-group of students
subsequently underwent a 2-week classroom trial of each ALD. Degree of
improvement from baseline [HA(s)/CI(s)] alone was assessed using teacher and
student Listening Inventory for Education-Revised (LIFE-R) questionnaires. STUDY
SAMPLE: In all, 20 students, aged 12.5-18.9 years, underwent speech recognition
assessment. In total, 10 of these participated in the classroom trial. Hearing
loss ranged from mild-to-profound levels. RESULTS: Performance in each ALD
configuration was higher than for HAs/CIs alone (p < 0.001). Teacher and student
LIFE-R results indicated significant improvement in listening/communication when
using the remote microphone in conjunction with HAs/CIs (p < 0.05). There was no
difference between the soundfield system and the baseline measurement (p > 0.05).
CONCLUSION: Speech recognition improvements were demonstrated with the
implementation of both remote microphones and soundfield systems. Both students
and teachers reported functional hearing advantages in the classroom when using
the remote microphone in concert with their standard hearing devices.
PMID- 27609146
TI - Unraveling cellular pathways contributing to drug-induced liver injury by
dynamical modeling.
AB - INTRODUCTION: Drug-induced liver injury (DILI) is a significant threat to human
health and a major problem in drug development. It is hard to predict due to its
idiosyncratic nature and which does not show up in animal trials. Hepatic
adaptive stress response pathway activation is generally observed in drug-induced
liver injury. Dynamical pathway modeling has the potential to foresee adverse
effects of drugs before they go in trial. Ordinary differential equation modeling
can offer mechanistic insight, and allows us to study the dynamical behavior of
stress pathways involved in DILI. Areas covered: This review provides an overview
on the progress of the dynamical modeling of stress and death pathways pertinent
to DILI, i.e. pathways relevant for oxidative stress, inflammatory stress, DNA
damage, unfolded proteins, heat shock and apoptosis. We also discuss the required
steps for applying such modeling to the liver. Expert opinion: Despite the strong
progress made since the turn of the century, models of stress pathways have only
rarely been specifically applied to describe pathway dynamics for DILI. We argue
that with minor changes, in some cases only to parameter values, many of these
models can be repurposed for application in DILI research. Combining both
dynamical models with in vitro testing might offer novel screening methods for
the harmful side-effects of drugs.
PMID- 27609147
TI - Electrochemical Impedance Spectroscopy of Ion-Selective Membranes: Artifacts in
Two-, Three-, and Four-Electrode Measurements.
AB - Electrochemical impedance spectroscopy is frequently used to characterize,
optimize, and monitor ion-selective membranes. However, because of the relatively
high resistance of ion-selective membranes, their impedance spectra often contain
artifacts that can cause misinterpretation. While in the high-frequency range
artifacts are often readily identifiable by the occurrence of inductive features
or negative resistances, artifacts are easy to overlook in the low-frequency
range, where telltale characteristics are typically missing. Some artifacts can
be avoided by the use of two-electrode cells, but this experimental design makes
it hard to distinguish the impedance of the ion-selective membrane from that of
the measuring electrodes. This work shows that experimental data can be analyzed
accurately with the use of models that account for the capacitive leakage present
in the reference channels of the impedance spectrometer. To test these models,
valinomycin-doped K+-selective membranes were studied by electrochemical
impedance spectroscopy with two-, three-, and four-electrode cells, using several
measuring electrodes with low to high impedances. The models were found to
correctly predict experimental data and provide an intuitive understanding of the
cause of the impedance artifacts. This understanding can be applied to design
electrochemical impedance spectroscopy experiments of ion-selective membranes
with three- and four-electrode cells that minimize artifacts.
PMID- 27609148
TI - Impact of the nursing home scale on residents' social engagement in South Korea.
AB - BACKGROUND: This study aimed to describe the levels of social engagement and to
examine the relationship between the nursing home scale groups and social
engagement in nursing homes in South Korea. METHODS: A total of 314 residents
were randomly selected from rosters provided by 10 nursing homes located in three
metropolitan areas in South Korea. The outcome variable was social engagement
measured by the Revised Index of Social Engagement (RISE), and the key
independent variable was the nursing home scale (small, medium, and large).
Individual factors (age, gender, activities of daily living and cognitive
function, and depressive symptoms) and organizational factors (location,
ownership, and staffing levels) were controlled in the model as covariates.
Multilevel logistic regression was used in this study. RESULTS: About half of the
residents (46%) in this study were not socially engaged in the nursing home
(RISE=0) where they resided. Controlling for individual- and organizational-level
factors, the nursing home facility size was a significant factor to predict the
likelihood of residents' social engagement, with that the residents in large
scale nursing homes being less likely to be socially engaged than those in medium
scale nursing homes (odds ratio = 0.457; p-value = 0.005). CONCLUSION: This study
supports evidence from previous studies that smaller-scale nursing homes are
likely to provide more person-centered care compared to larger-scale nursing
homes. Subsequent quality studies are needed to examine how the mechanisms for
how smaller-scale nursing homes can enhance residents' social engagement in terms
of care delivery processes.
PMID- 27609149
TI - Ultra-broadband Nonlinear Saturable Absorption for Two-dimensional Bi2TexSe3-x
Nanosheets.
AB - We report the ultra-broadband nonlinear optical (NLO) response of Bi2TexSe3-x
nanosheets produced by a facile solvothermal method. Our result show that the
extracted basic optical nonlinearity parameters of Bi2TexSe3-x nanosheets,
alphaNL, Imchi((3)), and FOM reach ~10(4) cm/GW, ~10(-8) esu and ~10(-13) esu cm,
respectively, which are several orders of magnitude larger than those of bulk
dielectrics. We further observed the excitation intensity dependence of the NLO
absorption coefficient and the NLO response sensitivity. The mechanisms of those
phenomena were proposed based on physical model. The wavelength dependence of the
NLO response of Bi2TexSe3-x nanosheets was investigated, and we determined that
the Bi2TexSe3-x nanosheets possess an ultra-broadband nonlinear saturable
absorption property covering a range from the visible to the near-infrared band,
with the NLO absorption insensitive to the excitation wavelength. This work
provide fundamental and systematic insight into the NLO response of Bi2TexSe3-x
nanosheets and support their application in photonic devices in the future.
PMID- 27609145
TI - Oxidative stress in prostate hyperplasia and carcinogenesis.
AB - Prostatic hyperplasia (PH) is a common urologic disease that affects mostly
elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or
prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to
influence the activities of inflammatory mediators and other cellular processes
involved in the initiation, promotion and progression of human neoplasms
including prostate cancer. Scientific evidence also suggests that micronutrient
supplementation may restore the antioxidant status and hence improve the clinical
outcomes for patients with BPH and PCa. This review highlights the recent studies
on prostate hyperplasia and carcinogenesis, and examines the role of OS on the
molecular pathology of prostate cancer progression and treatment.
PMID- 27609150
TI - Anti-inflammatory, analgesic and antioxidant activities of 3,4-oxo-isopropylidene
shikimic acid.
AB - Context 3,4-Oxo-isopropylidene-shikimic acid (ISA) is an analog of shikimic acid
(SA). SA is extracted from the dry fruit of Illicium verum Hook. f.
(Magnoliaceae), which has been used for treating stomachaches, skin inflammation
and rheumatic pain. Objective To investigate the anti-inflammatory, analgesic and
antioxidant activities of ISA. Materials and methods Analgesic and anti
inflammatory activities of ISA were evaluated using writhing, hot plate, xylene
induced ear oedema, carrageenan-induced paw oedema and cotton pellets-induced
granuloma test, meanwhile the prostaglandin E2 (PGE2) and malondialdehyde (MDA)
levels were assessed in the oedema paw tissue. ISA (60, 120 and 240 mg/kg in mice
model and 50, 120 and 200 mg/kg in rat model) was administered orally, 30 min
before induction of inflammation/pain. Additionally, ISA was administered for 12
d in rats from the day of cotton pellet implantation. The active oxygen species
scavenging potencies of ISA (10(-3)-10(-5) M) were evaluated by the electron spin
resonance spin-trapping technique. Results ISA caused a reduction of inflammation
induced by xylene (18.1-31.4%), carrageenan (7.8-51.0%) and cotton pellets (11.4
24.0%). Furthermore, ISA decreased the production of PGE2 and MDA in the rat paw
tissue by 1.0-15.6% and 6.3-27.6%, respectively. ISA also reduced pain induced by
acetic acid (15.6-48.9%) and hot plate (10.5-28.5%). Finally, ISA exhibited
moderate antioxidant activity by scavenging the superoxide radical and hydroxyl
radical with IC50 values of 0.214 and 0.450 MUg/mL, respectively. Discussion and
conclusion Our findings confirmed the anti-inflammatory, analgesic and
antioxidant activities of ISA.
PMID- 27609151
TI - Coronary Artery Disease - Reporting and Data System (CAD-RADS): An Expert
Consensus Document of SCCT, ACR and NASCI: Endorsed by the ACC.
AB - The intent of CAD-RADS - Coronary Artery Disease Reporting and Data System is to
create a standardized method to communicate findings of coronary CT angiography
(coronary CTA) in order to facilitate decision-making regarding further patient
management. The suggested CAD-RADS classification is applied on a per-patient
basis and represents the highest-grade coronary artery lesion documented by
coronary CTA. It ranges from CAD-RADS 0 (Zero) for the complete absence of
stenosis and plaque to CAD-RADS 5 for the presence of at least one totally
occluded coronary artery and should always be interpreted in conjunction with the
impression found in the report. Specific recommendations are provided for further
management of patients with stable or acute chest pain based on the CAD-RADS
classification. The main goal of CAD-RADS is to standardize reporting of coronary
CTA results and to facilitate communication of test results to referring
physicians along with suggestions for subsequent patient management. In addition,
CAD-RADS will provide a framework of standardization that may benefit education,
research, peer-review and quality assurance with the potential to ultimately
result in improved quality of care.
PMID- 27609152
TI - High-Output Heart Failure in Sickle Cell Anemia.
PMID- 27609153
TI - The Authors Reply.
PMID- 27609154
TI - CAD-RADS: A Giant First Step Toward a Common Lexicon?
PMID- 27609155
TI - Economic evaluation of health promotion for older people-methodological problems
and challenges.
AB - BACKGROUND: The support of health promotion activities for older people gains
societal relevance in terms of enhancing the health and well-being of older
people with a view to the efficient use of financial resources in the healthcare
sector. Health economic evaluations have become an important instrument to
support decision-making processes in many countries. Sound evidence on the cost
effectiveness of health promotion activities would encourage support for the
implementation of health promotion activities for older people. This debate
article discusses to what extent economic evaluation techniques are appropriate
to support decision makers in the allocation of resources regarding health
promotion activities for older people. We address the problem that the economic
evaluation of these interventions is hampered by methodological obstacles that
limit comparability, e.g. with economic evaluations of curative measures. Our
central objective is to describe and discuss the specific problems and challenges
entailed in the economic evaluation of health promotion activities especially for
older people with regard to their usefulness for informing decision making
processes. DISCUSSION: Beyond general problems concerning the economic evaluation
of health promotion, our discussion focusses on problems that pertain to the
analysis of cost and outcomes of health promotion interventions for older people.
With regard to costs these are general problems of economic evaluations, namely
the actual implementation of a societal perspective, the appropriate measurement
and valuation of informal caregiver time, the measurement and valuation of
productivity costs and costs incurred in added years of life. The main problems
concerning the identification and measurement of outcomes are related to the
identification of outcome parameters that, firstly, adequately reflect the broad
effects of health promotion interventions, especially social benefits that gain
importance for older people, and secondly, ensure a comparability of effects
across different age groups. In particular, the limitations of the widely used
QALY for older people are discussed and recently developed alternatives are
presented. CONCLUSIONS: The key conclusion of the article is that a comparison of
the effects of different health promotion initiatives between different age
groups by means of economic evaluation is not recommendable. Taking into account
the complex outcomes of health promotion interventions it has to be accepted that
the outcomes of these interventions will often not be comparable with clinical
interventions and have to be assessed differently.
PMID- 27609157
TI - Establishment of the Indian Chapter for Asian Eye Genetics Consortium.
PMID- 27609156
TI - Genes - they never go out of fashion!
PMID- 27609158
TI - Adult onset retinoblastoma.
AB - Retinoblastoma (RB) is the most common primary malignant intraocular tumor of
childhood presenting usually before 5 years of age. RB in adults older than 20
years is extremely rare. A literature search using PubMed/PubMed Central, Scopus,
Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date.
Over the past decade, there has been a significant increase in the number of such
reports, indicating heightened level of suspicion among ophthalmologists.
Compared to its pediatric counterpart, adult onset RB poses unique challenges in
diagnosis and treatment. This article summarizes available literature on adult
onset RB and its clinical and pathologic profile, genetics, association with
retinocytoma, diagnostics, treatment, and outcomes.
PMID- 27609159
TI - Delayed onset of congenital hereditary endothelial dystrophy due to compound
heterozygous SLC4A11 mutations.
AB - BACKGROUND: Congenital hereditary endothelial dystrophy (CHED) is an autosomal
recessive disorder characterized by bilateral, symmetrical, noninflammatory
corneal clouding (edema) present at birth or shortly thereafter. This study
reports on an unusual delayed presentation of CHED with compound heterozygous
SLC4A11 mutations. MATERIALS AND METHODS: A 45-year-old female, presenting with
bilateral decreased vision since childhood that deteriorated in the last 5 years,
was evaluated to rule out trauma, viral illness, chemical injury, glaucoma, and
corneal endothelial dystrophies. Tear sample was sent for herpes simplex viral
(HSV) antigen testing. Genomic DNA from peripheral blood was screened for
mutations in all exons of SLC4A11 by direct sequencing. Full-thickness
penetrating keratoplasty was done and corneal button was sent for
histopathological examination. RESULTS: Slit-lamp findings revealed bilateral
diffuse corneal edema and left eye spheroidal degeneration with scarring.
Increased corneal thickness (762 MUm and 854 MUm in the right and left eyes,
respectively), normal intraocular pressure (12 mmHg and 16 mmHg in the right and
left eyes, respectively), inconclusive confocal scan, and specular microscopy,
near normal tear film parameters, were the other clinical features. HSV
polymerase chain reaction was negative. Histopathological examination revealed
markedly thickened Descemet's membrane with subepithelial spheroidal
degeneration. SLC4A11 screening showed a novel variant p.Ser415Asn, reported
mutation p.Cys386Arg and two polymorphisms, all in the heterozygous state and not
identified in 100 controls. CONCLUSIONS: The study shows, for the first time,
compound heterozygous SLC4A11 mutations impair protein function leading to
delayed onset of the disease.
PMID- 27609160
TI - Nasolacrimal duct obstruction: Does it really increase the risk of amblyopia in
children?
AB - PURPOSE: To report the prevalence of amblyopia risk factors in children with
congenital nasolacrimal duct obstruction. METHODS: A retrospective review of
records of children with the diagnosis of congenital nasolacrimal duct
obstruction (NLDO), who underwent probing from January 2009 to October 2011, was
done. All of them underwent a complete ophthalmic evaluation including
cycloplegic refraction and strabismus evaluation before probing. RESULTS: A total
of 142 children were included in this study. The mean age at presentation was
22.38 months (sample standard deviation (SSD) - 15.88). Amblyopia risk factors
were defined according to two sets of guidelines: The American Association for
Pediatric Ophthalmology and Strabismus (AAPOS) referral criteria guidelines and
the new AAPOS Vision Screening Committee guidelines. Twenty-eight (20%) children
were found to have some form of amblyopia risk factor based on the referral
criteria prescribed by AAPOS. However, on applying modified guidelines described
by Donahue et al., to analyze the same cohort, 21 children were found to have
amblyogenic risk factors. Of these 28 children, 13 had significant astigmatism
(>1.50 D), 8 children had hypermetropia (>3.50 D), and six children had
anisometropia (>1.50 D). One child had significant cataract (media opacity >1
mm). None of the children in this series had either myopia or strabismus.
CONCLUSION: Prevalence of amblyopia risk factor was found to be 20% in our study
based on the older guidelines; however, it reduces to 14.78% by applying the
modified guidelines. Despite this reduction, importance of a comprehensive
ophthalmic examination including cycloplegic refraction in all children
presenting with NLDO cannot be overstated. A close follow-up of these children is
also essential to prevent the development of amblyopia.
PMID- 27609161
TI - The investigation on the role of mitochondrial fusion protein 1 in the
development of myopia.
AB - PURPOSE: The aim of this study is to preliminarily investigate the expression of
mitochondrial fusion protein 1 (MFN1) in a lens-induced animal myopia (LIM) model
and to explore the relationship between MFN1 and the visual development.
MATERIALS AND METHODS: MFN1 gene expression in guinea pigs was examined during
the development of minus LIM, 15 tri-colored guinea pigs were obtained, and one
eye of each pig was randomly selected and treated with -7.00D lenses. Ocular
refraction and axial length were collected before intervention and 1, 2, and 3
weeks after intervention. After the refraction and axial length measurements at
1, 2, and 3 weeks of lens intervention, five guinea pigs were randomly selected.
MFN1 expression in the retina of both eyes was tested by immunohistochemistry
technique. RESULTS: MFN1-positive cells could be observed in the retina of both
eyes. The positive cells in the LIM eyes were staining deeper, and much more
positive cells could be observed. Furthermore, MFN1-positive expression could be
seen mainly in ganglion cells after 1 week of minus lens intervention, and with
time extension, more and more positive cells appeared in the rod-cone cell and
bipolar cell layer, and this phenomenon could not be found in the normal control
eyes. CONCLUSION: This study suggested that MFN1 might be correlated to the
development of myopia.
PMID- 27609162
TI - Ultra-wide field angiography in the management of Eales disease.
AB - AIMS: This study aims to evaluate the use of ultra-wide field (UWF) angiography
in patients with Eales disease (ED). SETTINGS AND DESIGN: Prospective
observational case series in tertiary eye care center. SUBJECTS AND METHODS: This
study involved 17 patients diagnosed with ED, who underwent UWF fluorescein
angiography. The angiograms were analyzed to look for additional information as
compared to Early Treatment Diabetic Retinopathy Study seven standard field. The
impact of this information in the management of patients was analyzed. RESULTS:
24 eyes of 17 patients with mean age of 26.3 years were diagnosed with ED and
underwent UWF angiography. UWF fluorescein angiography was helpful in the
documentation of peripheral retinal changes (in 67% of eyes), exact localization
of capillary nonperfusion (CNP) (in 54% of eyes), and in determination of
vascular involvement (in 21% of eyes). In 33% of eyes, immediate treatment plan
changed because of changes picked up on UWF angiography. CONCLUSIONS: UWF
angiography helped in the better documentation, exact quantification, and
location of CNP areas and better determination of disease activity. UWF imaging
may play an important part in the management of patients with ED.
PMID- 27609164
TI - Phenotypic characterization of X-linked retinoschisis: Clinical,
electroretinography, and optical coherence tomography variables.
AB - AIMS: To study the phenotypic characteristics of X-linked retinoschisis (XLRS)
and report the clinical, electroretinogram (ERG), and optical coherence
tomography (OCT) variables in Indian eyes. DESIGN: A retrospective study.
MATERIALS AND METHODS: Medical records of 21 patients with retinoschisis who were
genetically confirmed to have RS1 mutation were reviewed. The phenotype
characterization included the age of onset, best-corrected visual acuity,
refractive error, fundus findings, OCT, and ERG. STATISTICAL ANALYSIS USED: Data
from both the eyes were used for analysis. A P < 0.05 was set as statistical
significance. Data were not normally distributed (P < 0.05, Shapiro wilk); hence,
nonparametric tests were used for statistical analysis. RESULTS: All were males
whose mean age of presentation was 9 years. Visual acuity was moderately impaired
(median 0.6 logMAR, interquartile range: 0.47, 1) in these eyes with a hyperopic
refractive error of median +1.75 Ds (interquartile range: +0.50 Ds, +4.25 Ds).
About 54.7% of the eyes had both foveal and peripheral schisis, isolated foveal
schisis was seen in 28.5% of the eyes, and schisis with retinal detachment was
seen in 16.6% of the eyes. The inner nuclear layer was found to be commonly
involved in the schisis, followed by outer nuclear and plexiform layers as
evident on OCT. On ERG, a- and b-wave amplitudes were significantly reduced in
eyes with foveal and peripheral schisis when compared to the eyes with only
foveal schisis (P < 0.05). CONCLUSIONS: XLRS has phenotypic heterogeneity as
evident on OCT, ERG, and clinical findings.
PMID- 27609163
TI - Further evidence for P59L mutation in GJA3 associated with autosomal dominant
congenital cataract.
AB - CONTEXT: Congenital cataracts are one of the common eye disorders leading to
visual impairment or blindness in children worldwide. We found a Chinese family
with autosomal dominant pulverulent cataract. AIMS: To identify the pathogenic
gene mutation in a Chinese family with autosomal dominant inherited pulverulent
cataract. SUBJECTS AND METHODS: After obtained informed consent, detailed
ophthalmic examinations were carried out; genomic DNAs were obtained from seven
family members in a three-generation Chinese family with three affected. All
exons of candidate genes were amplified by polymerase chain reaction and were
sequenced performed by bidirectional sequencing. RESULTS: By sequencing the
encoding regions of the candidate genes, a missense mutation (c. 176C>T) was
detected in gap junction protein alpha 3 genes (GJA3), which resulted in the
substitution of highly conserved proline by leucine at codon 59 (p.P59L). The
mutation co-segregated with all patients and was absent in 100 normal Chinese
controls. CONCLUSIONS: The study identified a missense mutation (c. 176C>T) in
GJA3 gene associated with autosomal dominant congenital pulverulent cataract in a
Chinese family. It gave further evidence of phenotype heterogeneity for P59L
mutation in GJA3 associated with congenital cataract.
PMID- 27609165
TI - Coats' disease of adult-onset in 48 eyes.
AB - BACKGROUND: Coats' disease diagnosed in adulthood is an idiopathic, retinal
exudative vascular disease without an inciting factor and has retinal features
different from the childhood disease. AIM: To describe clinical features,
treatment, and outcomes of eyes with Coats' disease first diagnosed in patients
35 years or older. MATERIALS AND METHODS: Retrospective chart review of patients
first diagnosed with Coats' disease at the age of 35 years or more at a tertiary
eye care center between January 1995 and 2012. Eyes with retinal exudation or
Coats'-like response from secondary causes were excluded. RESULTS: Forty-five of
646 patients (7%) diagnosed with Coats' disease had adult-onset disease. Mean age
at presentation was 47 years. Systemic hypertension was the most common (22%)
systemic association and decreased vision the predominant presenting feature
(83%). Localized (<6 clock h) presentation (74%) was unique to adults as against
diffuse involvement (69%) in children (P < 0.001). Eyes were treated with laser
photocoagulation 29 (60%), cryotherapy (4%), or both (2%) with surgical
intervention in three (6%) eyes. Following treatment eight (35%) eyes improved,
11 (48%) eyes were stable while four (12%) eyes worsened due to complications.
CONCLUSION: Adult-onset Coats' disease has less extensive involvement, more
benign natural course, and a more favorable treatment outcome as against the
childhood-onset disease. The bilateral presentation emphasizes the need for
regular follow-up to detect possible future involvement of the fellow eye.
PMID- 27609166
TI - Clinical outcome and regression patterns of retinoblastoma treated with systemic
chemoreduction and focal therapy: A prospective study.
AB - PURPOSE: To prospectively study the clinical outcome and regression patterns of
early retinoblastoma (Groups A and B) after systemic chemotherapy and focal
consolidation in Indian children. MATERIALS AND METHODS: Group A eyes were
treated with focal therapy (transpupillary thermotherapy/cryotherapy) and Group B
with systemic chemoreduction and focal therapy. Outcome measures were efficacy
and safety of treatment, risk factors for treatment failure, regression patterns,
and factors predictive of regression patterns. RESULTS: Of 119 eyes (216 tumors),
14 (11.8%) were Group A and 105 (88.2%) were Group B eyes. The mean follow-up was
22.6 months. Tumor control was achieved in 111/119 eyes (93.3% overall, 100%
Group A, 92.4% Group B). Eight Group B eyes (6.7%) had treatment failure. No
serious systemic side-effects were noted. Risk factors for failure included
larger tumors (P = 0.001) and proximity to posterior pole (P = 0.014). Regression
patterns were Type 4 (50.2%), Type 3 (31.7%), Type 1 (11.1%), and Type 2 (7%).
Factors predictive of Type 4 regression were smaller tumors, anterior location,
younger age; Type 3 regression was associated with larger tumors, macular
location, and older age. CONCLUSIONS: Systemic chemoreduction and focal therapy
provided effective tumor control in Indian children. Factors predictive of
regression patterns included age, tumor size and its location, and the modality
of treatment.
PMID- 27609167
TI - Intraoperative optical coherence tomography guided removal of premacular
hemorrhage in Valsalva retinopathy.
PMID- 27609168
TI - Co-existing ligneous conjunctivitis and IgG4-related disease.
AB - Herein, we elucidate that ligneous conjunctivitis (LC) was proved as an IgG4
related disease (IgG4-RD) by a series of pathologic studies from primary and
recurrent episodes of an LC patient. LC was diagnosed based on clinical
presentation and pathological appearance; furthermore, combined with serological
examination and immunohistochemical study, the case also conformed to the
diagnosis of IgG4-RD. The IgG4-RD, broadly discussed in recent times, is an
idiopathic disease entity with tissue fibrosis possibly involving multiple
organs. To the best of our knowledge, IgG4-RD has never been reported with LC. By
reporting the clinical course and literature review, we should pay attention to
the association between these two diseases.
PMID- 27609170
TI - Bilateral congenital infantile hemangioma of upper eyelids.
PMID- 27609169
TI - Two cases of myotonic dystrophy manifesting various ophthalmic findings with
genetic evaluation.
AB - We report two cases of myotonic dystrophy in one family; both diagnosed from
genetic analysis following ophthalmic indications, but before the manifestation
of systemic symptoms. A 39-year-old female visited our clinic for routine
examination. Mild ptosis, sluggish pupillary response, and bilateral snowflake
cataracts were found. Fundus examination revealed an increased cup-to-disc ratio
(CDR) in both eyes and a defect in the retinal nerve fiber layer in the right
eye. Intraocular pressure was low, but within the normal range in both eyes.
Because cataracts are characteristic of myotonic dystrophy, we suggested that her
14-year-old daughter, who did not have any systemic complaints, undergo
ophthalmic examination. She also had mild ptosis and snowflake cataracts. Both
patients underwent genetic evaluation and were diagnosed with myotonic dystrophy
caused by unstable expansion of cytosine-thymine-guanine trinucleotide repeats in
the dystrophia myotonica-protein kinase gene. Ophthalmologists can diagnose
myotonic dystrophy based on clinical and genetic findings, before the
manifestation of systemic abnormalities.
PMID- 27609171
TI - Comment on: A rare case of eyelid sarcoidosis presenting as an orbital mass.
PMID- 27609172
TI - Comment on: Systemic approach to managing vernal conjunctivitis in clinical
practice and severity grading system and treatment algorithm.
PMID- 27609173
TI - Authors' reply.
PMID- 27609174
TI - Comment on: An unusual presentation of nonarteritic ischemic optic neuropathy
with subretinal fluid treated with intravitreal bevacizumab.
PMID- 27609175
TI - Authors' reply.
PMID- 27609176
TI - Approach to tubercular disc edema.
PMID- 27609177
TI - Dual-Rim Sign in the Diagnosis of Cerebral Abscess.
PMID- 27609178
TI - Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium
difficile infection.
AB - BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be safe and
effective in treating refractory or relapsing C. difficile infection (CDI), but
its use has been limited by practical barriers. We recently reported a small
preliminary feasibility study using orally administered frozen fecal capsules.
Following these early results, we now report our clinical experience in a large
cohort with structured follow-up. METHODS: We prospectively followed a cohort of
patients with recurrent or refractory CDI who were treated with frozen,
encapsulated FMT at our institution. The primary endpoint was defined as clinical
resolution whilst off antibiotics for CDI at 8 weeks after last capsule
ingestion. Safety was defined as any FMT-related adverse event grade 2 or above.
RESULTS: Overall, 180 patients aged 7-95 years with a minimal follow-up of 8
weeks were included in the analysis. CDI resolved in 82 % of patients after a
single treatment, rising to a 91 % cure rate with two treatments. Three adverse
events Grade 2 or above, deemed related or possibly related to FMT, were
observed. CONCLUSIONS: We confirm the effectiveness and safety of oral
administration of frozen encapsulated fecal material, prepared from unrelated
donors, in treating recurrent CDI. Randomized studies and FMT registries are
still needed to ascertain long-term safety.
PMID- 27609179
TI - Monogenic polyarteritis: the lesson of ADA2 deficiency.
AB - The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease
characterised by an early onset vasculopathy with livedoid skin rash associated
with systemic manifestations, CNS involvement and mild immunodeficiency.This
condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye
Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes
for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different
mutations in CECR1 gene have been detected.The pathogenetic mechanism of DADA2 is
still unclear. ADA2 in a secreted protein mainly expressed by cells of the
myeloid lineage; its enzymatic activity is higher in conditions of hypoxia,
inflammation and oncogenesis. Moreover ADA2 is able to induce macrophages
proliferation and differentiation; it's deficiency is in fact associated with a
reduction of anti-inflammatory macrophages (M2). The deficiency of ADA2 is also
associated with an up-regulation of neutrophils-expressed genes and an increased
secretion of pro-inflammatory cytokines. The mild immunodeficiency detected in
many DADA2 patients suggests a role of this protein in the adaptive immune
response; an increased mortality of B cells and a reduction in the number of
memory B cells, terminally differentiated B cells and plasmacells has been
described in many patients. The lack of the protein is associated with
endothelium damage; however the function of this protein in the endothelial
homeostasis is still unknown.From the clinical point of view, this disease is
characterized by a wide spectrum of severity. Chronic or recurrent systemic
inflammation with fever, elevation of acute phase reactants and skin
manifestations (mainly represented by livedo reticularis) is the typical clinical
picture. While in some patients the disease is mild and skin-limited, others
present a severe, even lethal, disease with multi-organ involvement; the CNS
involvement is rather common with ischemic or hemorrhagic strokes. In many
patients not only the clinical picture but also the histopathologic features are
undistinguishable from those of systemic polyarteritis nodosa (PAN). Of note,
patients with an unusual phenotype, mainly dominated by clinical manifestations
suggestive for an immune-disrective condition, have been described.Due to its
rarity, the response to treatment of DADA2 is still anecdotal. While steroids can
control the disease's manifestations at high dosage, none of the common
immunosuppressive drugs turned out to be effective. Biologic drugs have been used
only in few patients, without a clear effectiveness; anti-TNF drugs are those
associated to a better clinical response. Hematopoietic stem cells
transplantation was effective in patients with a severe phenotype.
PMID- 27609181
TI - Erratum to "Calpains and neuronal damage in the ischemic brain: The swiss knife
in synaptic injury" [Progress in Neurobiology 143 (2016) 1-35].
PMID- 27609180
TI - IL-1beta induces IL-6 production and increases invasiveness and estrogen
independent growth in a TG2-dependent manner in human breast cancer cells.
AB - BACKGROUND: We previously reported that IL-6 and transglutaminase 2 (TG2) were
expressed in more aggressive basal-like breast cancer cells, and TG2 and IL-6
expression gave these cells stem-cell-like phenotypes, increased invasive
ability, and increased metastatic potential. In the present study, the underlying
mechanism by which IL-6 production is induced in luminal-type breast cancer cells
was evaluated, and TG2 overexpression, IL-1beta stimulation, and IL-6 expression
were found to give cancerous cells a hormone-independent phenotype. METHODS:
Luminal-type breast cancer cells (MCF7 cells) were stably transfected with TG2.
To evaluate the requirement for IL-6 neogenesis, MCF7 cells were stimulated with
various cytokines. To evaluate tumorigenesis, cancer cells were grown in a three
dimensional culture system and grafted into the mammary fat pads of NOD/scid/IL
2Rgamma(-/-) mice. RESULTS: IL-1beta induced IL-6 production in TG2-expressing
MCF7 cells through an NF-kB-, PI3K-, and JNK-dependent mechanism. IL-1beta
increased stem-cell-like phenotypes, invasiveness, survival in a three
dimensional culture model, and estrogen-independent tumor growth of TG2
expressing MCF7 cells, which was attenuated by either anti-IL-6 or anti-IL-1beta
antibody treatment. CONCLUSION: Within the inflammatory tumor microenvironment,
IL-1beta increases luminal-type breast cancer cell aggressiveness by stimulating
IL-6 production through a TG2-dependent mechanism.
PMID- 27609183
TI - Continuation and maintenance treatments for depression in older people.
AB - BACKGROUND: Depressive illness is common in old age. Prevalence in the community
of case level depression is around 15% and milder forms of depression are more
common. It causes significant distress and disability. The number of people over
the age of 60 years is expected to double by 2050 and so interventions for this
often long-term and recurrent condition are increasingly important. The causes of
late-life depression differ from depression in younger adults and so it is
appropriate to study it separately.This is an update of a Cochrane review first
published in 2012. OBJECTIVES: To examine the efficacy of antidepressants and
psychological therapies in preventing the relapse and recurrence of depression in
older people. SEARCH METHODS: We performed a search of the Cochrane Common Mental
Disorders Group's specialised register (the CCMDCTR) to 13 July 2015. The CCMDCTR
includes relevant randomised controlled trials (RCTs) from the following
bibliographic databases: The Cochrane Library (all years), MEDLINE (1950 to
date), EMBASE (1974 to date), and PsycINFO (1967 to date). We also conducted a
cited reference search on 13 July 2015 of the Web of Science for citations of
primary reports of included studies. SELECTION CRITERIA: Both review authors
independently selected studies. We included RCTs involving people aged 60 years
and over successfully treated for an episode of depression and randomised to
receive continuation and maintenance treatment with antidepressants,
psychological therapies, or a combination. DATA COLLECTION AND ANALYSIS: Two
review authors independently extracted data. The primary outcome for benefit was
recurrence rate of depression (reaching a cut-off on any depression rating scale)
at 12 months and the primary outcome for harm was drop-outs at 12 months.
Secondary outcomes included relapse/recurrence rates at other time points, global
impression of change, social functioning, and deaths. We performed meta-analysis
using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for
continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: This
update identified no further trials. Seven studies from the previous review met
the inclusion criteria (803 participants). Six compared antidepressant medication
with placebo; two involved psychological therapies. There was marked
heterogeneity between the studies.Comparing antidepressants with placebo on the
primary outcome for benefit, there was a statistically significant difference
favouring antidepressants in reducing recurrence compared with placebo at 12
months with a GRADE rating of low for quality of evidence (three RCTs, n = 247,
RR 0.67, 95% CI 0.54 to 0.82; number needed to treat for an additional beneficial
outcome (NNTB) 5). Comparing antidepressants with placebo on the primary outcome
for harms, there was no difference in drop-out rates at 12 months' follow-up,
with a GRADE rating of low.There was no significant difference between
psychological treatment and antidepressant in recurrence rates at 12 months (one
RCT, n = 53) or between combination treatment and antidepressant alone at 12
months. AUTHORS' CONCLUSIONS: This updated Cochrane review supports the findings
of the original 2012 review. The long-term benefits and harm of continuing
antidepressant medication in the prevention of recurrence of depression in older
people are not clear and no firm treatment recommendations can be made on the
basis of this review. Continuing antidepressant medication for 12 months appears
to be helpful with no increased harms; however, this was based on only three
small studies, relatively few participants, use of a range of antidepressant
classes, and clinically heterogeneous populations. Comparisons at other time
points did not reach statistical significance.Data on psychological therapies and
combined treatments were too limited to draw any conclusions on benefits and
harms.The quality of the evidence used in reaching these conclusions was low and
the review does not, therefore, offer clear guidance to clinicians and patients
on best practice and matching interventions to particular patient
characteristics.Of note, we identified no new studies that evaluated
pharmacological or psychological interventions in the continuation and
maintenance treatment of depression in older people. We are aware of studies
conducted since the previous review that included both older people and adults
under the age of 65 years, but these fall outside of the remit of this review. We
believe that there remains a need for studies solely recruiting older people,
particularly the 'older old' with comorbid medical problems. However, these
studies are likely to be challenging to conduct and may not, so far, have been
prioritised by funders.
PMID- 27609182
TI - Use of Smartphone for Verbal Autopsy.
AB - Traditionally, verbal autopsies (VA) are collected on paper-based questionnaires
and reviewed by physicians for cause of death assignment, it is resource
intensive and time consuming. The Population Health Metrics Research Consortium
VA questionnaires was made available on an Android-based application and cause of
death was derived using the Tariff method. Over one year, all adult deaths
occurring in 48 villages in 4 counties were identified and a VA interview was
conducted using the smartphone VA application. A total of 507 adult deaths were
recorded and VA interviews were conducted. Cardiovascular disease was the leading
cause of death (35.3%) followed by injury (14.6%) and neoplasms (13.5%). The
total cost of the pilot study was USD28 835 (USD0.42 per capita). The
interviewers found use of smartphones to conduct interviews to be easier. The
study showed that using a smartphone application for VA interviews was feasible
for implementation in rural China.
PMID- 27609184
TI - Conductance fluctuations in high mobility monolayer graphene: Nonergodicity, lack
of determinism and chaotic behavior.
AB - We have fabricated a high mobility device, composed of a monolayer graphene flake
sandwiched between two sheets of hexagonal boron nitride. Conductance
fluctuations as functions of a back gate voltage and magnetic field were obtained
to check for ergodicity. Non-linear dynamics concepts were used to study the
nature of these fluctuations. The distribution of eigenvalues was estimated from
the conductance fluctuations with Gaussian kernels and it indicates that the
carrier motion is chaotic at low temperatures. We argue that a two-phase
dynamical fluid model best describes the transport in this system and can be used
to explain the violation of the so-called ergodic hypothesis found in graphene.
PMID- 27609185
TI - The Use of Cocultured Mesenchymal Stem Cells with Tendon-Derived Stem Cells as a
Better Cell Source for Tendon Repair.
AB - The management of tendon tissue injury presents a significant clinical challenge
due to the unique properties of tendons. Cell-based therapy provides a new
alternative for regenerating functional tendons, such as in tendon rupture
repair, but largely remains at the preclinical research stage. A cell source for
graft preparation is essential for successful clinic application. In this study,
a novel cell coculture system of bone marrow mesenchymal stem cells (BMSCs) and
tendon-derived stem cells (TDSCs) was developed and investigated. BMSCs and TDSCs
were cultured separately or in combination at ratios of 20:1, 10:1, 5:1, and 1:1
in vitro, and the cocultured cells showed an enhanced proliferation and
collagenous protein production. The coculture system promoted tenogenic
differentiation with enhanced tenogenic marker gene expression and collagen
matrix production, particularly in the groups with a ratio of 1:1. Using a rat
patellar tendon window injury model, we demonstrated that the cell sheets formed
by cocultured cells promoted tendon healing significantly, compared to those with
a single-cell source. Our study suggests that BMSCs and TDSCs cocultured at the
1:1 ratio may be an improved cell source/preparation for tendon tissue
engineering.
PMID- 27609186
TI - IgG4-related disease causing facial nerve and optic nerve palsies: Case report
and literature review.
AB - IgG4-related disease (IgG4-RD) is increasingly being recognized as an entity
effecting the head and neck region. Although most commonly seen with salivary
gland or paranasal sinus involvement, IgG4-RD may also involve the temporal bone
and skull base. We report a rare care of a 61-year-old female with IgG4-RD
presenting as synchronous lesions of the middle ear and middle cranial fossa with
polyneuropathy of cranial nerves II, VI, and VII. Initial histopathological
evaluation of her resected ear mass suggested a benign inflammatory process but
no specific diagnosis. Her symptoms progressed over 10months prompting re
evaluation of the specimen and consideration of the IgG4-RD diagnosis. Key
pathologic features included prominent lymphoplasmacytic population, storiform
fibrosis, obliterative phlebitis, and IgG4 specific staining. The patient was
treated with high-dose intravenous and oral steroids but was transitioned to
azathioprine secondary to steroid-induced myopathy. Radiographic studies before
and after treatment reveal marked improvement of the intracranial and
extracranial disease. Correspondingly, her cranial neuropathies resolved. A high
degree of clinical suspicion is necessary to diagnosis IgG4-RD. The diagnosis can
be supported by elevated serum IgG, elevated IgG index, and pathognomonic
histopathological findings. Primary treatment is with corticosteroids. However,
immunotherapy using azathioprine or rituximab can be utilized in recurrent
disease or patients with steroid intolerance.
PMID- 27609187
TI - Alpha-2 agonists for sedation in mechanically ventilated neurocritical care
patients: a systematic review protocol.
AB - BACKGROUND: Sedation is an important consideration in the care of the
neurocritically ill patient. It provides anxiety and relief, facilitates
procedures and nursing tasks, and minimizes intolerance of mechanical
ventilation. Alpha-2 agonists such as dexmedetomidine and clonidine have been
shown to be an effective alternative in the general critical care population by
reducing duration of mechanical ventilation and length of stay in the intensive
care unit (ICU), as compared to traditional sedative agents such as propofol or
benzodiazepines. However, there is a paucity of literature detailing their
utility and safety in neurocritical care, a population that presents unique
considerations for management of global and cerebral hemodynamics, agitation, and
facilitation of neurological assessments. The objective of this review is to
assess the efficacy and safety of alpha-2 agonists for non-procedural sedation in
mechanically ventilated brain-injured patients. METHODS: We will search the
Embase and MEDLINE databases for all randomized controlled trials, prospective
and retrospective cohort studies examining neurocritically ill adult patients
aged 18 years and older who are on mechanical ventilation and receiving alpha-2
agonists for non-procedural sedation. Primary outcomes of interest include effect
on mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral
perfusion pressure (CPP). Secondary outcomes include adverse events, duration of
mechanical ventilation, 30-day mortality, ICU length of stay, incidence of
delirium, and quality of sedation. Continuous outcomes will be presented as means
and mean differences and discrete counting events will be presented as event
rates. Pre-defined criteria for heterogeneity are provided for determination of
pooling eligibility. Where appropriate, we will pool estimates for individual
outcomes. Planned subgroup analyses include specific alpha-2 agonist agent, study
design, clinical diagnosis, dosing regimen, and use of adjunctive agents. Quality
of evidence for the recommendation will be assessed using the Grading of
Recommendations, Assessment, Development and Evaluation (GRADE) approach where
appropriate. DISCUSSION: This systematic review will summarize the evidence on
the efficacy and safety for the use of alpha-2 agonists as sedative agents in the
neurocritical care population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42016037045.
PMID- 27609188
TI - Pulse pressure variation shows a direct linear correlation with tidal volume in
anesthetized healthy patients.
AB - BACKGROUND: The settings of mechanical ventilation, like tidal volume (VT),
occasionally need to be adjusted in the process of anesthesia for some special
reasons. The aim of this study was therefore to assess the relationship between
pulse pressure variations (PPVs) in different settings of VT in anesthetized
healthy patients under mechanical ventilation. METHODS: Sixty nine ASA I-II
patients scheduled for gastrointestinal surgery under general anesthesia were
included in this prospective study. All the patients were ventilated at a VT of
6, 8 or 10 ml/kg (predicted body weight) with no positive end expiratory pressure
(PEEP) in a random order after intubation. PPV, mean arterial blood pressure, and
other hemodynamic and respiratory parameters were recorded in each VT setting
respectively after Partial Pressure of End-Tidal Expiration Carbon Dioxide
(PetCO2) maintained between 30 mmHg and 40 mmHg by changing Respiratory Rate (RR)
before incision. RESULTS: The values of PPV at different settings of VT showed a
tight correlation between each other (6 vs. 8 ml/kg: r = 0.97, P < 0.0001; 6
vs.10 ml/kg: r = 0.95, P < 0.0001; 8 vs. 10 ml/kg: r = 0.98, P < 0.0001,
respectively). CONCLUSION: There is a direct linear correlation between PPVs at
different tidal volumes in anesthetized ASA I-II patients. PPV in any of the 3 VT
settings (6, 8 or 10 ml/kg) can deduce that in any other 2 settings. Further
studies are needed to explore the effect of intraoperative confounders for this
knowledge to be clinically applied. TRIAL REGISTRATION: NCT01950949 ,
www.clinicaltrials.gov , July 26, 2013.
PMID- 27609190
TI - Induction of apoptosis and G2/M arrest by ampelopsin E from Dryobalanops towards
triple negative breast cancer cells, MDA-MB-231.
AB - BACKGROUND: Several compounds isolated from Dryobalanops have been reported to
exhibit cytotoxic effects to several cancer cell lines. This study investigated
the cytotoxic effects, cell cycle arrest and mode of cell death in ampelopsin E
treated triple negative cells, MDA-MB-231. METHODS: Cytotoxicity of ampelopsin E,
ampelopsin F, flexuosol A, laevifonol, Malaysianol A, Malaysianol D and
nepalensinol E isolated from Dryobalanops towards human colon cancer HT-29,
breast cancer MDA-MB-231 and MCF-7, alveolar carcinoma HeLa and mouse embryonic
fibroblast NIH/3 T3 cells were determined by MTT assay. The cells were treated
with the compounds (0.94-30 MUM) for 72 h. The mode of cell death was evaluated
by using an inverted light microscope and annexin V/PI analysis. Cell cycle
analysis was performed by using a flow cytometer. RESULTS: Data showed that
ampelopsin E was most cytotoxic toward MDA-MB-231 with the IC50 (50 % inhibition
of cell viability compared to control) of 14.5 +/- 0.71 MUM at 72 h. Cell
shrinkage, membrane blebbing and formation apoptotic bodies characteristic of
apoptosis were observed following treatment with ampelopsin E. The annexin V/PI
flow cytometric analysis further confirmed that ampelopsin E induced apoptosis in
MDA-MB-231 cells. Cell cycle analysis revealed that ampelopsin E induced G2/M
phase cell cycle arrest in the cells. CONCLUSION: Ampelopsin E induced apoptosis
and cell cycle arrest in MDA-MB-231 cells. Therefore, ampelopsin E has the
potential to be developed into an anticancer agent for treatment of triple
negative breast cancer.
PMID- 27609191
TI - A surveillance study of the current status of reirradiation and patterns of
practice.
AB - The aim of this study was to survey the current status of reirradiation (Re-RT)
and patterns of practice in Japan. An email questionnaire was sent to Kansai
Cancer Therapist Group partner institutions, using questions similar to those in
the Canadian radiation oncologist (RO) survey (2008). A total of 34 ROs from 28
institutions returned the survey. All 28 institutions experienced Re-RT cases in
2014. However, 26 of the 28 institutions (93%) reported difficulty in obtaining
Re-RT case information from their respective databases. Responses from 19
institutions included the number of Re-RT cases; this rose from 183 in the period
2005-2009 (institution median = 4; 2-12.9) to 562 in the period 2010-2014
(institution median = 26; 2-225). Important considerations for indication of Re
RT were age (65%), performance status (83%), life expectancy (70%), absence of
distant metastases (67%), and interval since previous treatment (73%). Previous
total radiation dose (48%), volume of tissue irradiated (72%), and the
biologically equivalent dose (BED; 68.5%) were taken into account during Re-RT
planning. These factors were similar to those considered in the Canadian survey;
however, the present study did not consider age. In eight site-specific
scenarios, barring central nervous system recurrence, more than 90% of ROs agreed
to perform Re-RT, which was higher than the percentage observed in the Canadian
survey. Re-RT cases have increased in number and aroused interest among ROs in
this decade of advanced technology. However, consensus building to establish
guidelines for the practice and prospective evaluation of Re-RT is required.
PMID- 27609192
TI - The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus
based computed tomographic atlas for defining regional lymph node stations in
radiotherapy for lung cancer.
AB - The purpose of this study was to develop a consensus-based computed tomographic
(CT) atlas that defines lymph node stations in radiotherapy for lung cancer based
on the lymph node map of the International Association for the Study of Lung
Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group
(JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11
were illustrated on axial CT images. Subsequently, a joint committee of the Japan
Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology
(JASTRO) was formulated to revise this draft. The committee consisted of four
radiation oncologists, four thoracic surgeons and three thoracic radiologists.
The draft prepared by the JROSG project group was intensively reviewed and
discussed at four meetings of the committee over several months. Finally, we
proposed definitions for the regional lymph node stations and the consensus-based
CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO.
This resulted in the first official CT atlas for defining regional lymph node
stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In
conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC
lymph node map, was established.
PMID- 27609189
TI - Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and
Breast Cancer Recurrence in a Preclinical Model.
AB - Background: Responses to endocrine therapies vary among patients with estrogen
receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine
disrupting compounds might explain these variations. Methods: We describe a novel
ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance.
Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol
(EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary
tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in
EE2 offspring) or without 1.2 g/kg valproic acid and 5 mg/kg hydralazine (n = 24
tumors in the controls and n = 32 tumors in EE2 offspring) in the female
offspring, was assessed. One-sided Chi2 tests were used to calculate P values.
Comparisons of differentially expressed genes between mammary tumors in in utero
EE2-exposed and control rats, and between anti-estrogen-resistant LCC9 and
sensitive LCC1 human breast cancer cells, were also performed. Results: In our
preclinical model, 54.2% of mammary tumors in the control rats exhibited a
complete response to TAM, of which 23.1% acquired resistance with continued anti
estrogen treatment and recurred. Mammary tumors in the EE2 offspring were
statistically significantly less likely to respond to TAM (P = .047) and recur (P
= .007). In the EE2 offspring, but not in controls, adding valproic acid and
hydralazine to TAM prevented recurrence (P < .001). Three downregulated and
hypermethylated genes (KLF4, LGALS3, MICB) and one upregulated gene (ETV4) were
identified in EE2 tumors and LCC9 breast cancer cells, and valproic acid and
hydralazine normalized the altered expression of all four genes. Conclusions:
Resistance to TAM may be preprogrammed by in utero exposure to high estrogen
levels and mediated through reversible epigenetic alterations in genes associated
with epithelial-mesenchymal transition and tumor immune responses.
PMID- 27609193
TI - Computer-assisted framework for machine-learning-based delineation of GTV regions
on datasets of planning CT and PET/CT images.
AB - We have proposed a computer-assisted framework for machine-learning-based
delineation of gross tumor volumes (GTVs) following an optimum contour selection
(OCS) method. The key idea of the proposed framework was to feed image features
around GTV contours (determined based on the knowledge of radiation oncologists)
into a machine-learning classifier during the training step, after which the
classifier produces the 'degree of GTV' for each voxel in the testing step.
Initial GTV regions were extracted using a support vector machine (SVM) that
learned the image features inside and outside each tumor region (determined by
radiation oncologists). The leave-one-out-by-patient test was employed for
training and testing the steps of the proposed framework. The final GTV regions
were determined using the OCS method that can be used to select a global optimum
object contour based on multiple active delineations with a LSM around the GTV.
The efficacy of the proposed framework was evaluated in 14 lung cancer cases
[solid: 6, ground-glass opacity (GGO): 4, mixed GGO: 4] using the 3D Dice
similarity coefficient (DSC), which denotes the degree of region similarity
between the GTVs contoured by radiation oncologists and those determined using
the proposed framework. The proposed framework achieved an average DSC of 0.777
for 14 cases, whereas the OCS-based framework produced an average DSC of 0.507.
The average DSCs for GGO and mixed GGO were 0.763 and 0.701, respectively,
obtained by the proposed framework. The proposed framework can be employed as a
tool to assist radiation oncologists in delineating various GTV regions.
PMID- 27609194
TI - Vesigenurtacel-L (HS-410) in the management of high-grade nonmuscle invasive
bladder cancer.
AB - Unlike other malignancies, the death rate of bladder cancer has not declined in
several decades, highlighting the need for new treatment options. In the emerging
era of immunotherapy, therapeutic cancer vaccines are an attractive option to
cure, control and prevent cancer. Despite this, finding a feasible and
efficacious vaccine platform has proven elusive across all malignancies.
Vesigenurtacel-L is the first whole cell, allogeneic vaccine intended to treat
high-grade, nonmuscle invasive bladder cancer. This type of vaccine technology
for bladder cancer is novel, and has the potential to be both economically and
logistically feasible.
PMID- 27609195
TI - Reinforcement of tungsten carbide grains by nanoprecipitates in cemented
carbides.
AB - In contrast to the conventional method that obtains a high fracture strength of
tungsten carbide-cobalt (WC-Co) cemented carbides by reducing WC grain size to
near-nano or nanoscale, a new approach has been developed to achieve ultrahigh
fracture strength by strengthening the WC grains through precipitate
reinforcement. The cemented carbides were prepared by liquid-state sintering the
in situ synthesized WC-Co composite powders with a little excess carbon and pre
milled Cr3C2 particles having different size scales. It was found that the
nanoscale dispersed particles precipitate in the WC grains, which mainly have a
coherent or semi-coherent interface with the matrix. The pinning effect of the
nanoparticles on the motion of dislocations within the WC grains was observed.
The mechanisms for the precipitation of nanoparticles in the WC grains were
discussed, based on which a new method to enhance the resistance against the
transgranular fracture of cemented carbides was proposed.
PMID- 27609197
TI - Effect of age and carcass weight on quality traits of m. rectus abdominis from
Charolais heifers.
AB - In practice cattle may be slaughtered at different combinations of age and
weight. As each of these factors could affect meat quality traits, the present
work aimed to identify which combination can be expected to increase overall meat
quality of m. rectus abdominis of Charolais heifers. Totally, 40 heifers were
slaughtered either at 26+/-1 or at 36+/-1 months of age. Young heifers were
sampled at two different carcass weights (349+/-12 and 394+/-8 kg). Old heifers
were also sampled at two different carcass weights (397+/-6 and 451+/-9 kg). The
m. rectus abdominis was excised 24 h postmortem to determine metabolic enzyme
activities, myosin heavy-chain isoform proportions, lipid contents, collagen
content and collagen solubility. Shear force measurements were evaluated on raw
and broiled meat after 14 days of ageing. Meat quality traits scored between 0
and 10 by sensory analysis. Increasing slaughter age from 26 to 36 months had no
impact on either raw/broiled shear force (0.31?P?0.47) and/or meat quality traits
(0.62?P?0.91) or on physicochemical properties of heifer's meat samples.
Increasing carcass weight for a similar slaughter age of 26 months had also
impact neither on meat quality traits (0.52?P?0.91) nor on muscular properties.
On the contrary, increasing carcass weight for a similar slaughter age of 36
months had induced a decrease of muscular shear force (raw muscle; P=0.009) and a
concomitant decrease of total collagen content (P=0.03). Nevertheless, no
significant impact on meat quality traits was revealed by the sensorial panel
(0.13?P?0.49). Metabolic enzyme activities (0.13?P?0.86) and myosin heavy-chain
proportions (0.13?P?0.96) were not significantly impacted by slaughter age and
carcass weight. Thus, the impact of increasing carcass weight and/or slaughter
age in young Charolais heifers has a limited impact on meat quality traits and
associated muscular characteristics. Modulating heifer's cycles (age and/or
carcass weight in the studied range) appears to be a way to answer to the
numerous marketing chains, without penalising meat quality traits.
PMID- 27609196
TI - Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: What is
missing?
AB - The cardiotoxicity of certain chemotherapeutic agents is now well-established,
and has led to the development of the field of cardio-oncology, increased cardiac
screening of cancer patients, and limitation of patients' maximum cumulative
chemotherapeutic dose. The effect of chemotherapeutic regimes on the heart
largely involves cardiomyocyte death, leading to cardiomyopathy and heart
failure, or the induction of arrhythmias. Of these cardiotoxic drugs, those
resulting in clinical cardiotoxicity can range from 8 to 26% for doxorubicin, 7
28% for trastuzumab, or 5-30% for paclitaxel. For tyrosine kinase inhibitors, QT
prolongation and arrhythmia, ischemia and hypertension have been reported in 2
35% of patients. Furthermore, newly introduced chemotherapeutic agents are
commonly used as part of changed combinational regimens with significantly
increased incidence of cardiotoxicity. It is widely believed that the mechanism
of action of these drugs is often independent of their cardiotoxicity, and the
basis for why these drugs specifically affect the heart has yet to be
established. The genetic rationale for why certain patients experience
cardiotoxicity whilst other patients can tolerate high chemotherapy doses has
proven highly illusive. This has led to significant genomic efforts using
targeted and genome-wide association studies (GWAS) to divine the pharmacogenomic
cause of this predilection. With the advent of human induced pluripotent stem
cell-derived cardiomyocytes (hiPSC-CMs), the putative risk and protective role of
single nucleotide polymorphisms (SNPs) can now be validated in a human model.
Here we review the state of the art knowledge of the genetic predilection to
chemotherapy-induced cardiotoxicity and discuss the future for establishing and
validating the role of the genome in this disease.
PMID- 27609198
TI - Determinants of agreement between proposed therapeutic windows of platelet
function tests in vulnerable patients.
AB - AIMS: Therapeutic windows for residual platelet reactivity in patients with
coronary artery disease on P2Y12 inhibitors were proposed in a consensus
document. We aimed to explore the level of agreement between windows for
different platelet function tests (PFTs) used to classify patients in low,
optimal, and high on-treatment platelet reactivity categories, and to identify
variables contributing to the level of agreement. METHODS AND RESULTS: In this
explorative clinical study, the VerifyNow P2Y12, Multiplate adenosine diphosphate
(ADP), and light transmission aggregometry (LTA) 20 MUmol/L ADP were performed
simultaneously in 145 consecutive vulnerable patients. Measurements were
performed within 6 months of percutaneous intervention. Patients were considered
vulnerable if they had >=2 risk factors for bleeding or ischaemic events. Window
agreement between PFT pairs was slight to moderate. Multiplate-VerifyNow agreed
in 72 patients (50%), kappa = 0.41; VerifyNow-LTA agreed in 76 patients (52%),
kappa = 0.36; and LTA-Multiplate agreed in 64 patients (44%), kappa = 0.20.
Several variables including the type of P2Y12 inhibitor, aspirin, haemoglobin
level, platelet count, age, and previous stroke significantly influenced
agreement between PFTs. CONCLUSIONS: Our results suggest that the PFTs, with
accompanying therapeutic windows, are not interchangeable when determining the
response to antiplatelet therapy in vulnerable coronary artery disease patients
on P2Y12 inhibitors. Hence, the type of PFT can directly affect the treatment
strategy, which may be especially relevant for patients with multiple factors
influencing individual PFTs and thereby test agreement.
PMID- 27609199
TI - Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic
intermittent hypoxia in mice.
AB - Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory
instability. Our previous work showed that chronic hypoxia induces the oxygen
sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region
and the pre-Botzinger complex (pre-BotC). We therefore examined the effect of CIH
on time course of induced expression of HO-1 within these regions and determined
whether the induction of HO-1 correlated with changes in respiratory, sigh
frequency, and sympathetic responses (spectral analysis of heart rate) to acute
hypoxia (10% O2) during 10 days of exposure to CIH in chronically instrumented
awake wild-type (WT) and HO-1 null mice (HO-1-/-). HO-1 was induced within the C1
and pre-BotC regions after 1 day of CIH. There were no significant differences in
the baseline respiratory parameters between WT and HO-1-/- Prior to CIH, acute
hypoxia increased respiratory frequency in both WT and HO-1-/-; however, minute
diaphragm electromyogram activity increased in WT but not HO-1-/- The hypoxic
respiratory response after 1 and 10 days of CIH was restored in HO-1-/- CIH
resulted in an initial significant decline in 1) the hypoxic sigh frequency
response, which was restored in WT but not HO-1-/-, and 2) the baseline
sympathetic activity in WT and HO-1-/-, which remained stable subsequently in WT
but not in HO-1-/- We conclude that 1) CIH induces expression of HO-1 in the C1
and pre-BotC regions within 1 day and 2) HO-1 is necessary for hypoxia
respiratory response and contributes to the maintenance of the hypoxic sigh
responses and baseline sympathetic activity during CIH.
PMID- 27609200
TI - Energy substrate utilization with and without exogenous carbohydrate intake in
boys and men exercising in the heat.
AB - Little is known about energy yield during exercise in the heat in boys compared
with men. To investigate substrate utilization with and without exogenous
carbohydrate (CHOexo) intake, seven boys [11.2 +/- 0.2 (SE) yr] and nine men
(24.0 +/- 1.1 yr) cycled (4 * 20-min bouts) at a fixed metabolic heat production
(Hp) per unit body mass (6 W/kg) in a climate chamber (38 degrees C and 50%
relative humidity), on two occasions. Participants consumed a 13C-enriched 8% CHO
beverage (CARB) or placebo beverage (CONT) in a double-blinded, counterbalanced
manner. Substrate utilization was calculated for the last 60 min of exercise.
CHOexo oxidation rate (2.0 +/- 0.3 vs. 2.5 +/- 0.2 mg.kg fat-free mass-1.min-1, P
= 0.02) and CHOexo oxidation efficiency (12.8 +/- 0.6 vs. 16.0 +/- 0.9%, P =
0.01) were lower in boys compared with men exercising in the heat. Total
carbohydrate (CHOtotal), endogenous CHO (CHOendo), and total fat (Fattotal)
remained stable in boys and men (P > 0.05) during CARB, whereas CHOtotal
oxidation rate decreased (P < 0.001) and Fattotal oxidation rate increased over
time similarly in boys and men during CONT (P < 0.001). The relative contribution
of CHOexo to total energy yield increased over time in both groups (P < 0.001).
In conclusion, endogenous substrate metabolism and the relative contribution of
fuels to total energy yield were not different between groups. The ingestion of a
CHO beverage during exercise in the heat may be as beneficial for boys as men to
spare endogenous substrate.
PMID- 27609202
TI - "Tighter fit" theory-physiologists explain why "higher altitude" and jugular
occlusion are unlikely to reduce risks for sports concussion and brain injuries.
PMID- 27609201
TI - Healthy aging does not compromise the augmentation of cardiac function during
heat stress.
AB - During heat stress, stroke volume is maintained in young adults despite
reductions in cardiac filling pressures. This is achieved by a general
augmentation of cardiac function, highlighted by a left and upward shift of the
Frank-Starling relation. In contrast, healthy aged adults are unable to maintain
stroke volume during heat stress. We hypothesized that this would be associated
with a lack of shift in the Frank-Starling relation. Frank-Starling relations
were examined in 11 aged [69 +/- 4 (SD) yr, 4 men/7 women] and 12 young (26 +/- 5
yr, 6 men/6 women) adults during normothermic and heat stress (1.5 degrees C
increase in core temperature) conditions. During heat stress, increases in
cardiac output were attenuated in aged adults (+2.5 +/- 0.3 (95% CI) vs. young:
+4.5 +/- 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30
+/- 4 vs. young: +42 +/- 5 beats/min, P < 0.01). In contrast to our hypothesis, a
leftward shift of the Frank-Starling relation maintained stroke volume during
heat stress in aged adults (76 +/- 8 vs. normothermic: 74 +/- 8 ml, P = 0.38)
despite reductions in cardiac filling pressure (6.6 +/- 1.0 vs. normothermic: 8.9
+/- 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to
return cardiac filling pressure during heat stress to normothermic values, which
resulted in a greater stroke volume for a given cardiac filling pressure in both
groups. These results demonstrate that the Frank-Starling relation shifts during
heat stress in healthy young and aged adults, thereby preserving stroke volume
despite reductions in cardiac filling pressures.
PMID- 27609203
TI - Sarcopenia, frailty and mortality: the evidence is growing.
PMID- 27609205
TI - Drug use in persons with and without Alzheimer's disease aged 90 years or more.
AB - BACKGROUND: increasing number of persons reach very high age but few studies have
investigated their drug use patterns. OBJECTIVE: to compare drug use among
persons with Alzheimer's disease (AD) aged >=90 years to persons without AD with
similar age and to younger persons with AD. DESIGN: register-based data were from
the MEDALZ cohort including all community-dwelling persons diagnosed with AD 2005
11 in Finland. They were identified from Special Reimbursement register. One
comparison person without AD was matched with age-, gender- and region of
residence. Persons with AD were divided to those aged >=90 years (N = 3,319) and
<90 years (N = 63,896) at the time of AD diagnoses. Drug use was analysed during
a 6-month period after AD diagnosis. Logistic regression models were constructed
to compare prevalence of drug use. RESULTS: compared to comparison persons
without AD with similar age, persons with AD aged >=90 years were more likely to
use antipsychotics (comorbidity adjusted odds ratio [aOR] 4.84, 95% CI 4.07-5.75;
CI, confidence intervals) and antidepressants (aOR 2.45, 95% CI 2.14-2.80). In
addition, persons with AD used more likely preventive drugs such as statins (aOR
1.20, 95% CI 1.04-1.38) and bisphosphonates (aOR 1.33, 95% CI 1.13-1.57).
Compared to younger persons with AD, those aged >=90 years were more likely to
use psychotropic drugs (55.6% vs. 48.4%, aOR 1.30, 95% CI 1.21-1.39), including
antipsychotics (aOR 1.40, 95% CI 1.28-1.52) and BZDRs (aOR 1.34, 95% CI 1.25
1.45). CONCLUSIONS: the vulnerable oldest persons with AD receive a substantial
burden of psychotropics.
PMID- 27609208
TI - Cognitive decline in patients with atrial fibrillation: can we do something about
it?
PMID- 27609210
TI - Fixing the broken image of care homes, could a 'care home innovation centre' be
the answer?
AB - The UK has many excellent care homes that provide high-quality care for their
residents; however, across the care home sector, there is a significant need for
improvement. Even though the majority of care homes receive a rating of 'good'
from regulators, still significant numbers are identified as requiring
'improvement' or are 'inadequate'. Such findings resonate with the public
perceptions of long-term care as a negative choice, to be avoided wherever
possible-as well as impacting on the career choices of health and social care
students. Projections of current demographics highlight that, within 10 years,
the part of our population that will be growing the fastest will be those people
older than 80 years old with the suggestion that spending on long-term care
provision needs to rise from 0.6% of our Gross Domestic Product in 2002 to 0.96%
by 2031. Teaching/research-based care homes have been developed in the USA,
Canada, Norway, the Netherlands and Australia in response to scandals about care,
and the shortage of trained geriatric healthcare staff. There is increasing
evidence that such facilities help to reduce inappropriate hospital admissions,
increase staff competency and bring increased enthusiasm about working in care
homes and improve the quality of care. Is this something that the UK should think
of developing? This commentary details the core goals of a Care Home Innovation
Centre for training and research as a radical vision to change the culture and
image of care homes, and help address this huge public health issue we face.
PMID- 27609213
TI - Plasmodium falciparum and Mycoplasma pneumoniae co-infection presenting with
cerebral malaria manifesting orofacial dyskinesia and haemophagocytic
lymphohistiocytosis.
AB - BACKGROUND: Malaria is a mosquito-borne infectious disease with diverse clinical
manifestations caused by a parasitic protozoan of the genus Plasmodium. Complex
inter-relationships between Mycoplasma species and Plasmodium parasites have been
previously noted in vitro. This is the first report of Plasmodium falciparum and
Mycoplasma pneumoniae co-infection in a human host presenting with cerebral
malaria manifesting orofacial dyskinesias and haemophagocytic
lymphohistiocytosis. CASE PRESENTATION: A 55-year-old Sri Lankan man with a
recent visit to South Africa presented with an acute febrile illness, cough and
worsening dyspnoea with alveolar-interstitial infiltrates on chest radiography.
Serological evaluation confirmed a diagnosis of Mycoplasma infection. He
subsequently developed encephalopathy with orofacial dyskinesia. A diagnosis of
severe P. falciparum infection with significant parasitaemia was established.
Peripheral blood cytopaenia occurred due to haemophagocytic lymphohistiocytosis
in the bone marrow. Complete clinical and haematological recovery was achieved
with intravenous artesunate. CONCLUSIONS: Plasmodium falciparum and Mycoplasma
pneumoniae co-infection occurring in vivo manifests clinical features that are
plausibly a result of the interaction between the two microorganisms. This is the
first report of orofacial dyskinesia in either infection.
PMID- 27609212
TI - Case report of homozygous deletion involving the first coding exons of GCNT2
isoforms A and B and part of the upstream region of TFAP2A in congenital
cataract.
AB - BACKGROUND: Congenital cataracts affect 3-6 per 10,000 live births and represent
one of the leading causes of blindness in children. Congenital cataracts have a
strong genetic component with high heterogeneity and variability. CASE
PRESENTATION: Analysis of whole exome sequencing data in a patient affected with
congenital cataracts identified a pathogenic deletion which was further defined
by other techniques. A ~98-kb homozygous deletion of 6p24.3 involving the first
three exons (two non-coding and one coding) of GCNT2 isoform A, the first exon
(coding) of GCNT2 isoform B, and part of the intergenic region between GCNT2 and
TFAP2A was identified in the patient and her brother while both parents were
found to be heterozygous carriers of the deletion. The exact breakpoints were
identified and revealed the presence of Alu elements at both sides of the
deletion, thus indicating Alu-mediated non-homologous end-joining as the most
plausible mechanism for this rearrangement. Recessive mutations in GCNT2 are
known to cause an adult i blood group phenotype with congenital cataracts in some
cases. The GCNT2 gene has three differentially expressed transcripts, with GCNT2B
being the only isoform associated with lens function and GCNT2C being the only
isoform expressed in red blood cells based on earlier studies; previously
reported mutations/deletions have either affected all three isoforms (causing
blood group and cataract phenotype) or the C isoform only (causing blood group
phenotype only). Dominant mutations in TFAP2A are associated with syndromic
anophthalmia/microphthalmia and other ocular phenotypes as part of Branchio
Ocular-Facial-Syndrome (BOFS). While the patients do not fit a diagnosis of BOFS,
one sibling demonstrates mild overlap with the phenotypic spectrum, and therefore
an effect of this deletion on the function of TFAP2A cannot be ruled out.
CONCLUSIONS: To the best of our knowledge, this is the first case reported in
which disruption of the GCNT2 gene does not involve the C isoform. The congenital
cataracts phenotype in the affected patients is consistent with the previously
defined isoform-specific roles of this gene. The GCNT2-TFAP2A region may be prone
to rearrangements through Alu-mediated non-homologous end-joining.
PMID- 27609214
TI - Impact of piperacillin-tazobactam shortage on meropenem use: implications for
antimicrobial stewardship programs.
AB - Drug shortages pose a clear detriment to antimicrobial stewardship (AS) efforts.
Our objective was to evaluate the effect of a piperacillin-tazobactam shortage on
meropenem use, related costs, and associated changes in AS activity. A quasi
experimental quality improvement review compared adult patients receiving
meropenem >=72h three months pre-shortage and three months during the shortage.
320 patients were included (pre-shortage: 103; shortage: 217). Baseline
characteristics were similar, but the length of stay was slightly longer in pre
shortage [19 (11-32) days] versus shortage [16 (11-32) days] (p=0.094). In pre
shortage and shortage, median days of therapy and estimated meropenem cost were 7
(5-11) and 7 (5-10) and $309.93 ($173.60-$507.03) and $255.30 ($204.24-$424.31),
respectively (p=0.411 and p=0.050). Frequency of ID consultation was similar
(16.8% in pre- and 25.3% in shortage, p=0.091). AS interventions increased during
the shortage period (99 in pre-shortage and 205 in shortage). De-escalation
occurred in 19.4% versus 32.7% of the patients in pre-shortage and shortage
(p=0.014). The piperacillin-tazobactam shortage was associated with a 111%
increase in meropenem prescriptions despite active AS, but was not associated
with changes in mortality, length of therapy, or meropenem costs. AS should be
aware that shortages may require proactive countermeasures to avoid inappropriate
antimicrobial use during shortage periods.
PMID- 27609216
TI - PrEP, Truvada, and Gilead.
PMID- 27609217
TI - Manifestations of Mucolipidosis III in the hand: avascular necrosis of multiple
carpal bones.
PMID- 27609218
TI - Clinical application of a free radial artery superficial palmar branch flap for
soft-tissue reconstruction of digital injuries.
AB - : Unsuccessful reconstruction of injured fingers can lead to poor outcomes. The
aim of this article was to investigate the clinical application of the radial
artery superficial palmar branch flap for soft-tissue reconstruction of the
finger. We treated 125 patients with various finger injuries who underwent free
radial artery superficial palmar branch flap reconstruction between October 2010
and March 2015. There were 46 distal finger injuries, 25 distal finger amputation
following failed replantation and 54 palmar digital injuries with tendon, bone or
joint exposure requiring soft-tissue reconstruction. Of the 125 cases, 114 flap
reconstructions were considered successful. We believe that a free radial artery
superficial palmar branch flap transfer is credible and useful for reconstructing
various finger injuries. LEVEL OF EVIDENCE: III.
PMID- 27609215
TI - In Vivo Characterization of ARN14140, a Memantine/Galantamine-Based Multi-Target
Compound for Alzheimer's Disease.
AB - Alzheimer's disease (AD) is a chronic pathological condition that leads to
neurodegeneration, loss of intellectual abilities, including cognition and
memory, and ultimately to death. It is widely recognized that AD is a
multifactorial disease, where different pathological cascades (mainly amyloid and
tau) contribute to neural death and to the clinical outcome related to the
disease. The currently available drugs for AD were developed according to the one
target, one-drug paradigm. In recent times, multi-target strategies have begun to
play an increasingly central role in the discovery of more efficacious candidates
for complex neurological conditions, including AD. In this study, we report on
the in vivo pharmacological characterization of ARN14140, a new chemical entity,
which was obtained through a multi-target structure-activity relationship
campaign, and which showed a balanced inhibiting profile against the
acetylcholinesterase enzyme and the NMDA receptor. Based on the initial promising
biochemical data, ARN14140 is here studied in mice treated with the amyloidogenic
fragment 25-35 of the amyloid-beta peptide, a consolidated non-transgenic AD
model. Sub-chronically treating animals with ARN14140 leads to a prevention of
the cognitive impairment and of biomarker levels connected to neurodegeneration,
demonstrating its neuroprotective potential as new AD agent.
PMID- 27609219
TI - Q&A: Gordon Mills on Neomorphs in Cancer.
AB - Gordon Mills, MD, PhD, chair of systems biology at The University of Texas MD
Anderson Cancer Center in Houston, discusses a third category of genomic
aberrations besides oncogene activation or tumor suppressor inactivation:
neomorphs, or mutations that rewire cellular signaling in unexpected ways, with
important functional consequences.
PMID- 27609220
TI - Folate intakes from diet and supplements may place certain Canadians at risk for
folic acid toxicity.
AB - To examine the prevalence of folate inadequacy and toxicity based on usual
intakes from food and supplements, as well as biomarkers of folate, secondary
data analyses were performed using cross-sectional, nationally representative
data from the Canadian Community Health Survey, Cycle 2.2 (n 32 776), as well as
biomarker data from the Canadian Health Measures Survey, Cycles 1, 2 and 3 (n 15
754). On the basis of unfortified food sources, Canadians would struggle to
consume adequate amounts of folate. When folate intakes from all food sources
were considered, the overall prevalence of folate inadequacy was low across all
age/sex groups, with the exception of females >70 years. However, >10 % of
supplement users were above the tolerable upper intake level, increasing to
almost 18 % when overage factors were accounted for. In addition, between 20 and
52 % of supplement users had elevated erythrocyte folate concentrations,
depending on the cut-off used. Results from this study suggest that insufficient
dietary intakes of folate in Canadians have been ameliorated because of the
fortification policy, although folate inadequacy still exists across all age
groups. However, supplement users appear to be at an increased risk of folic acid
(FA) overconsumption as well as elevated erythrocyte folate. As such, the general
population should be informed of the potential risks of FA overconsumption
resulting from supplement use. This study suggests a need for more careful
assessment of the risks and benefits of food fortification, particularly
fortification above mandated levels, and FA supplement use in the general
population.
PMID- 27609222
TI - Haemostasis - an indispensable, cross-sectional medical discipline.
PMID- 27609223
TI - Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen
induced arthritis.
AB - BACKGROUND: Prokineticin 2 (PK2) expression is upregulated in mice with collagen
induced arthritis (CIA), an animal model of rheumatoid arthritis. The purpose of
our study was to investigate the effects of PK2 inhibition on CIA. METHODS: PK2,
prokineticin receptor (PKR) 1, and PKR2 mRNA transcripts in the joints of CIA
mice were measured by real-time PCR on Days 21, 28, and 35 (n = 15/day).
Localization of PKR1 and PKR2 proteins was examined immunohistochemically. PKRA7,
a PK2 antagonist, was administered intraperitoneally for 2 weeks to CIA mice, and
the severity of arthritis was compared between treated (n = 12) and untreated (n
= 12) mice. The gene expression levels of inflammatory cytokines IL-1beta, IL-6,
TNF-alpha, and VEGF were also measured by real-time PCR and compared between
treated (n = 6) and untreated (n = 6) CIA mice. The data was statistically
analyzed, and P values of less than 0.05 were considered significant. RESULTS: In
the thickened synovial membrane, PKR1 protein was expressed in infiltrating
neutrophils, while PKR2 expression was found in macrophage-like mononuclear
cells. PK2 gene expression was significantly more pronounced on Days 28 and 35
than on Day 21 (2.15 and 2.03 versus 1.00, P = 0.0311 and 0.0247; Dunn's multiple
comparison). PKR2 gene expression levels were significantly higher on Days 28 and
35 compared to Day 21 (25.4 and 39.3 versus 1.0, P = 0.002 and < 0.0001; Dunn's
multiple comparison). Administration of PKRA7 suppressed the severity of
arthritis (P < 0.001; two-way analysis of variance). A gene expression analysis
of inflammatory cytokines revealed significantly reduced IL-1beta and lL-6
expression in the joints of PKRA7-treated mice compared to untreated mice (0.1
versus 1.0, P = 0.0043 and 0.04 versus 1.0, P = 0.0022, respectively; Mann
Whitney test). CONCLUSIONS: PK2 inhibition suppressed arthritis in mice with CIA.
PMID- 27609221
TI - Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational
nicotine exposure in adult offspring.
AB - BACKGROUND: Epidemiological and animal studies have reported that prenatal
nicotine exposure (PNE) leads to obesity and type-2 diabetes in offspring.
Central leptin-melanocortin signaling via hypothalamic arcuate
proopiomelanocortin (POMC) neurons is crucial for the regulation of energy and
glucose balance. Furthermore, hypothalamic POMC neurons were recently found to
mediate the anorectic effects of nicotine through activation of acetylcholine
receptors. Here, we hypothesized that PNE impairs leptin-melanocortinergic
regulation of energy balance in first-generation offspring by altering expression
of long non-coding RNAs (lncRNAs) putatively regulating development and/or
function of hypothalamic POMC neurons. METHODS: C57BL/6J females were exposed ad
libitum to nicotine through drinking water and crossed with C57BL/6J males.
Nicotine exposure was sustained during pregnancy and discontinued at parturition.
Offspring development was monitored from birth into adulthood. From the age of 8
weeks, central leptin-melanocortin signaling, diabetes, and obesity
susceptibility were assessed in male offspring fed a low-fat or high-fat diet for
16 weeks. Nicotine-exposed and non-exposed C57BL/6J females were also crossed
with C57BL/6J males expressing the enhanced green fluorescent protein
specifically in POMC neurons. Transgenic male offspring were subjected to laser
microdissections and RNA sequencing (RNA-seq) analysis of POMC neurons for
determination of nicotine-induced gene expression changes and regulatory
lncRNA/protein-coding gene interactions. RESULTS: Contrary to expectation based
on previous studies, PNE did not impair but rather enhanced leptin
melanocortinergic regulation of energy and glucose balance via POMC neurons in
offspring. RNA-seq of laser microdissected POMC neurons revealed only one
consistent change, upregulation of Gm15851, a lncRNA of yet unidentified
function, in nicotine-exposed offspring. RNA-seq further suggested 82 cis
regulatory lncRNA/protein-coding gene interactions, 19 of which involved coding
genes regulating neural development and/or function, and revealed expression of
several previously unidentified metabolic, neuroendocrine, and neurodevelopment
pathways in POMC neurons. CONCLUSIONS: PNE does not result in obesity and type 2
diabetes but instead enhances leptin-melanocortinergic feeding and body weight
regulation via POMC neurons in adult offspring. PNE leads to selective
upregulation of Gm15851, a lncRNA, in adult offspring POMC neurons. POMC neurons
express several lncRNAs and pathways possibly regulating POMC neuronal
development and/or function.
PMID- 27609224
TI - Reactions between nitrosopersulfide and heme proteins.
AB - When nitrosothiols react with excess hydrogen sulfide, H2S, they form several
intermediates including nitrosopersulfide (SSNO-). The stability and importance
of this species has been debated. While some data suggest SSNO- can be a
relatively stable source of NO activity, others suggest that the species degrades
too quickly. We find the species to be relatively stable in isolation. Due to the
abundance and prominence of iron-containing proteins throughout the human body,
it is important to establish the interaction of ferrous- and ferric-iron
containing proteins with SSNO-. Study of the reactions of SSNO- with heme
proteins can also provide information about the potential in vivo stability and
spontaneous reactivity of this species. We have used time-resolved electron
paramagnetic resonance and UV-Vis absorption spectroscopy to study the reactions
of SSNO- with heme proteins. Iron-nitrosyl hemoglobin is formed when SSNO- is
reacted with deoxyhemoglobin and deoxygenated methemoglobin, suggesting NO
formation from SSNO-. However, the yields of nitrosyl hemoglobin in reactions of
SSNO- with deoxyhemoglobin are much less than when SSNO- is reacted with
deoxygenated methemoglobin. Very little to no nitrosyl hemoglobin is formed when
SSNO- is reacted carboxyhemoglobin, HbCO, and when SSNO- is reacted with
oxygenated hemoglobin, minimal methemoglobin is formed Taken together, these data
confirm the release of NO, but indicate a vacant heme is necessary to facilitate
a direct heme-SSNO- reaction to form substantial NO. These data also suggest that
the ferric iron in methemoglobin potentiates SSNO- reactivity. These results
could potentially impact NO and sulfide bioavailability and reactivity.
PMID- 27609225
TI - Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO
pathway and ROS homeostasis.
AB - Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine
metabolism and as a source of reactive oxygen species (ROS). In addition, this
enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of
inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO
generation is of particular importance during certain conditions when NO
bioavailability is diminished due to reduced activity of endothelial NOS (eNOS)
or increased oxidative stress, including aging and cardiovascular disease. The
exact interplay between NOS- and XOR-derived NO generation is not fully
elucidated yet. The aim of the present study was to investigate if eNOS
deficiency is associated with changes in XOR expression and activity and the
possible impact on nitrite, NO and ROS homeostasis. Plasma levels of nitrate and
nitrite were similar between eNOS deficient (eNOS-/-) and wildtype (wt) mice. XOR
activity was upregulated in eNOS-/- compared with wt, but not in nNOS-/-, iNOS-/-
or wt mice treated with the non-selective NOS inhibitor L-NAME. Following an
acute dose of nitrate, plasma nitrite increased more in eNOS-/- compared with wt,
and this augmented response was abolished by the selective XOR inhibitor
febuxostat. Livers from eNOS-/- displayed higher nitrite reducing capacity
compared with wt, and this effect was attenuated by febuxostat. Dietary
supplementation with nitrate increased XOR expression and activity, but
concomitantly reduced superoxide generation. The latter effect was also seen in
vitro after nitrite administration. Treatment with febuxostat elevated blood
pressure in eNOS-/-, but not in wt mice. A high dose of dietary nitrate reduced
blood pressure in naive eNOS-/- mice, and again this effect was abolished by
febuxostat. In conclusion, eNOS deficiency is associated with an upregulation of
XOR facilitating the nitrate-nitrite-NO pathway and decreasing the generation of
ROS. This interplay between XOR and eNOS is proposed to play a significant role
in NO homeostasis and blood pressure regulation.
PMID- 27609226
TI - 3,3'-diindolylmethane mitigates total body irradiation-induced hematopoietic
injury in mice.
AB - We have reported that hematopoietic system injury induced by total body
irradiation (TBI) leads to generation of intracellular reactive oxygen species
(ROS) and DNA damage, which are ameliorated by antioxidant agents. In the present
study, we reported that administration of DIM, a potent antioxidant agent, not
only protected mice against TBI-induced lethality, also ameliorated TBI-induced
hematopoietic injury. The latter effect was probably attributable to DIM's
inhibition of TBI-induced increases in ROS production in hematopoietic stem cells
(HSCs) and the phosphorylation of histone H2AX (gamma-H2AX). In particular, DIM
led to significant improvements in bone marrow (BM) HSC frequency, hematopoietic
progenitor cell (HPC) clonogenic function, and multilineage engraftment after
transplantation. A downregulation of NADPH oxidase 4 (NOX4) and an upregulation
of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)
expression were observed following DIM treatment. Notably, the anti-apoptotic
potential of DIM was correlated with increased expression of the anti-apoptotic
protein Bcl-2 and decreased expression of the pro-apoptotic protein Bax. These
findings suggest that DIM attenuates TBI-induced hematopoietic injury through the
inhibition of both oxidative stress in HSCs and hematopoietic cell apoptosis.
Furthermore, we demonstrated that DIM protected BM hematopoietic cells against
ionizing radiation and led to increased clonogenicity in vitro. Therefore, DIM
has the potential to be used as an effective radioprotectant to ameliorate TBI
induced hematopoietic injury.
PMID- 27609228
TI - Structural features of DNA are conserved in the promoter region of orthologous
genes across different strains of Helicobacter pylori.
AB - Promoter regions play a key role in the process of transcription initiation and
gene expression, hence promoter identification is an inherent component of the
genome annotation process. Identification and characterization of promoters in
fully sequenced genomes is a challenging and complex task. An analysis of
sequence-dependent DNA structural properties in the promoter region of
orthologous and non-orthologous genes can help in characterizing promoters and
also provide insights into transcription initiation. Various structural
properties, such as duplex stability, protein-induced bendability and intrinsic
curvature of promoter sequences have been calculated and compared for 10
different strains of Helicobacter pylori genomes, and it is found that promoter
regions in orthologous and non-orthologous genes show distinct trends for these
properties, with orthologous genes showing sharper low-stability peak, lower
bendability and higher curvature. The average GC content of orthologous genes is
higher than that of non-orthologous genes, and relative stability-based promoter
annotation tool PromPredict performs better for orthologous genes than non
orthologous genes. The characteristic sequence-dependent structural properties of
promoters show significant differences between orthologous and non-orthologous
genes. Interestingly, these structural properties of promoters are conserved, but
the genes themselves vary in their evolutionary selection rate.
PMID- 27609227
TI - Salvianolic acid A alleviates ischemic brain injury through the inhibition of
inflammation and apoptosis and the promotion of neurogenesis in mice.
AB - Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn
great attention for its potent bioactivities against ischemia-induced injury both
in vitro and in vivo. In this study, we evaluated SalA's protective effects
against acute ischemic stroke by inducing middle cerebral artery
occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA
(50 and 100MUg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved
their moving activity, and ameliorated the severity of brain infarction and
apoptosis seen in the mice by diminishing pathological changes such as the
extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the
activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B
(NF-kappaB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited
cortical infarction and promoted the expression of neurogenesis protein near the
peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by
compromising the activation of GSK3beta and p25/Cdk5, which in turn upregulated
beta-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation
of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor.
We conclude that SalA blocks inflammatory responses by impairing NF-kappaB
signaling, thereby limiting inflammation/nitrosative stress and preserving the
integrity of the BBB; SalA also concomitantly promotes neurogenesis-related
protein expression by compromising GSK3beta/Cdk5 activity to enhance the
expression levels of beta-catenin/DCX and Bcl-2 for neuroprotection.
PMID- 27609229
TI - Secretion of M2e:HBc fusion protein by Lactobacillus casei using Cwh signal
peptide.
AB - The ability to serve as a delivery vehicle for various interesting biomolecules
makes lactic acid bacteria (LAB) very useful in several applications. In the
medical field, recombinant LAB expressing pathogenic antigens at different
cellular locations have been used to elicit both mucosal and systemic immune
responses. Expression-secretion vectors (ESVs) with a signal peptide (SP) are
pivotal for protein expression and secretion. In this study, the genome sequence
of Lactobacillus casei ATCC334 was explored for new SPs using bioinformatics
tools. Three new SPs of the proteins Cwh, SurA and SP6565 were identified and
used to construct an ESV based on our Escherichia coli-L. casei shuttle vector,
pRCEID-LC13.9. Functional testing of these constructs with the green fluorescence
protein (GFP) gene showed that they could secrete the GFP. The construct with
CwhSP showed the highest GFP secretion. Consequently, CwhSP was selected to
develop an ESV construct carrying a synthetic gene encoding the extracellular
domain of the matrix 2 protein fused with the hepatitis B core antigen (M2e:HBc).
This ESV was shown to efficiently express and secrete the M2e:HBc fusion protein.
The identified SPs and the developed ESVs can be exploited for expression and
secretion of homologous and heterologous proteins in L. casei.
PMID- 27609230
TI - Phage vB_BsuP-Goe1: the smallest identified lytic phage of Bacillus subtilis.
AB - Currently, interest in phage science is on the rise again as this subject remains
largely unexplored, and its potential diversity mainly untapped. Here, we present
phage vB_BsuP-Goe1, a new isolate that infects Bacillus subtilis The phage forms
round plaques with a matt outline on agar plates containing a B. subtilis Delta6
lawn. Transmission electron microscopy and genomic analyses revealed that phage
vB_BsuP-Goe1 belongs to the Podoviridae family as a new member of the
Phi29likevirus genus. The phage genome comprises 18 379 bp that encode for one
RNA gene and for 24 open reading frames. Phage vB_BsuP-Goe1 clusters with phage
B103 and Nf within the Phi29likevirus genus and is currently the smallest member
of this genus. Genome comparison with members of the Phi29likevirus genus reveals
a conserved gene set coding for essential replication and morphogenesis functions
while the genome extremities are more prone to gene and genome organisation
variability.
PMID- 27609231
TI - The risk of low concentrations of antibiotics in agriculture for resistance in
human health care.
AB - The contribution of antibiotic resistance originally selected for in the
agricultural sector to resistance in human pathogens is not known exactly, but is
unlikely to be negligible. It is estimated that 50% to 80% of all antibiotics
used are applied in agriculture and the remainder for treating infections in
humans. Since dosing regimens are less controlled in agriculture than in human
health care, veterinary and environmental microbes are often exposed to sublethal
levels of antibiotics. Exposure to sublethal drug concentrations must be
considered a risk factor for de novo resistance, transfer of antimicrobial
resistant (AMR) genes, and selection for already existing resistance. Resistant
zoonotic agents and commensal strains carrying AMR genes reach the human
population by a variety of routes, foodstuffs being only one of these. Based on
the present knowledge, short treatments with the highest dose that does not cause
unacceptable side-effects may be optimal for achieving therapeutic goals while
minimizing development of resistance. Novel approaches such as combination or
alternating therapy are promising, but need to be explored further before they
can be implemented in daily practice.
PMID- 27609232
TI - Efficient plasmid transduction to Staphylococcus aureus strains insensitive to
the lytic action of transducing phage.
AB - The transduction mediated by bacteriophages is considered to be one of the
primary driving forces in horizontal gene transfer in staphylococci, which is
crucial to their adaptation and successful evolution. For a transduction to be
effective, it is generally accepted that the recipient strain should be
susceptible to the transducing phage. In this study, we demonstrate that the
plasmid DNAs are effectively transduced into the recipient Staphylococcus aureus
strains in spite of their insensitivity to the lytic action of the transducing
phage, provided that these phages adsorb effectively to the bacterial cells. The
tetracycline and penicillinase plasmids were transduced to insensitive laboratory
and clinical strains by bacteriophages phi29, phi52A and phi80alpha as well as by
prophage phi53 and naturally occurring prophages induced from donor lysogenic
strains. Comparable frequencies of transduction were achieved in both phage
sensitive and phage-insensitive recipient strains. We have demonstrated that such
mechanisms as the restriction of DNA and lysogenic immunity which are responsible
for insensitivity of cells to phages may not be a barrier to the transfer,
maintenance and effective spread of plasmids to a wider range of potential
recipients in the staphylococcal population.
PMID- 27609234
TI - Effects of rainfall on oil droplet size and the dispersion of spilled oil with
application to Douglas Channel, British Columbia, Canada.
AB - Raindrops falling on the sea surface produce turbulence. The present study
examined the influence of rain-induced turbulence on oil droplet size and
dispersion of oil spills in Douglas Channel in British Columbia, Canada using
hourly atmospheric data in 2011-2013. We examined three types of oils: a light
oil (Cold Lake Diluent - CLD), and two heavy oils (Cold Lake Blend - CLB and
Access Western Blend - AWB). We found that the turbulent energy dissipation rate
produced by rainfalls is comparable to what is produced by wind-induced wave
breaking in our study area. With the use of chemical dispersants, our results
indicate that a heavy rainfall (rain rate>20mmh-1) can produce the maximum
droplet size of 300MUm for light oil and 1000MUm for heavy oils, and it can
disperse the light oil with fraction of 22-45% and the heavy oils of 8-13%,
respectively. Heavy rainfalls could be a factor for the fate of oil spills in
Douglas Channel, especially for a spill of light oil and the use of chemical
dispersants.
PMID- 27609233
TI - The main pigment of the dormant Mycobacterium smegmatis is porphyrin.
AB - Upon transition of Mycobacterium smegmatis into the dormant state, accumulation
of a dark brown fluorescent pigment was observed. This pigment gave bright red
fluorescence in both cells and the culture medium. Based on 1H-NMR, MALDI and UV
spectra, the fluorescent compounds, extracted from the culture medium as well as
from the dormant cells, were concluded to be a mixture of free coproporphyrin III
and uroporphyrin III and their corresponding methyl esters. A possible
significance of porphyrin pigment accumulation in the dormant cells is discussed.
PMID- 27609235
TI - A study of wrecked Dovekies (Alle alle) in the western North Atlantic highlights
the importance of using standardized methods to quantify plastic ingestion.
AB - Quantification of plastic ingestion across a range of seabirds is required to
assess the prevalence of plastics in marine food webs. We quantified plastic
ingestion in beached Dovekies (Alle alle), following a wreck in Newfoundland,
Canada. Of 171 birds, 30.4% had ingested plastic (mean 0.81+/-0.30 SE pieces per
bird, mass 0.005+/-0.002 SE g per bird). Most plastics were fragments of
polyethylene and polypropylene. Surprisingly, 37% were burned or melted,
indicating a previously unreported source of ingested plastics (incinerated
waste). We found no relationship between plastic ingestion and age, sex or body
condition. By comparing our results with a similar nearby study, we illustrate
the need for researchers to adopt standardized methods for plastic ingestion
studies. We underline the importance of using histological techniques to reliably
identify gastric pathologies, and advise caution when inferring population level
trends in plastic ingestion from studies of emaciated, wrecked birds.
PMID- 27609236
TI - Can gelatinous zooplankton influence the fate of crude oil in marine
environments?
AB - Gelatinous zooplankton are known for their capacity to excrete copious amounts of
mucus that can be utilized by other organisms. The release of mucus is
exacerbated by stressful conditions. Despite the recognized importance of
cnidarian mucus to production and material flux in marine ecosystems, the role of
gelatinous zooplankton in influencing the fate of oil spills is unknown. In this
study we used laboratory experiments to observe the influence of mucus from the
moon jellyfish (Aurelia aurita) on the aggregation and degradation of crude oil.
The results show that jellyfish swimming in a dispersed solution of oil droplets
produced copious amounts of mucus and the mucus aggregates that were shed by the
animals contained 26 times more oil than the surrounding water. Incubation
experiments showed that hydrocarbon degrading bacteria cell densities more than
doubled in the presence of mucus and after 14days, resulted in a significant
increase in oil degradation. These results suggest that jellyfish can aggregate
dispersed oil droplets and embed them within a matrix that favors hydrocarbon
degrading bacteria. While this study lends support to the hypothesis that the
presence of gelatinous zooplankton can impact oil spills large scale mesocosm
studies will be needed to fully quantify the influence on a natural system.
PMID- 27609237
TI - Teasing in younger and older children with microtia before and after ear
reconstruction.
AB - This study prospectively measured teasing and emotional adjustment before and
after ear reconstruction in younger and older children with microtia.
Participants with isolated microtia (n = 28) were divided into two groups by age
at surgery, with a younger group aged 3-5 years (n = 13) with a mean age of 4.0
(0.71) years at the time of surgery and an older group aged 6-10 years old (n =
15) with a mean age of 7.87 (1.30) years. Children and their parents were
interviewed preoperatively and a year after surgery about teasing and emotions
about their ear(s). Teasing began between the ages of 2.4-4.8 years. A third of
the younger group and all of the older group reported preoperative teasing.
Before surgery, the older group reported higher rates of negative emotions about
their ear(s) and teasing was correlated for all ages with feeling sad, worried,
and mad about their ear(s). After surgery, teasing and negative emotions
significantly decreased with increased happiness about their ear(s).
Postoperative teasing was correlated with trying to hide their ear(s). There were
significant interactions from before to after surgery based on surgery age for
frequency of teasing, sadness, and feeling mad, with the older group showing
relatively greater change postoperatively. Teasing and negative emotions about
their ear(s) decreased for all ages after surgery, with a potential protective
factor seen in younger surgery age.
PMID- 27609238
TI - Erratum.
PMID- 27609239
TI - Predicting Suicidal Behavior From Longitudinal Electronic Health Records.
AB - OBJECTIVE: The purpose of this article was to determine whether longitudinal
historical data, commonly available in electronic health record (EHR) systems,
can be used to predict patients' future risk of suicidal behavior. METHOD:
Bayesian models were developed using a retrospective cohort approach. EHR data
from a large health care database spanning 15 years (1998-2012) of inpatient and
outpatient visits were used to predict future documented suicidal behavior (i.e.,
suicide attempt or death). Patients with three or more visits (N=1,728,549) were
included. ICD-9-based case definition for suicidal behavior was derived by expert
clinician consensus review of 2,700 narrative EHR notes (from 520 patients),
supplemented by state death certificates. Model performance was evaluated
retrospectively using an independent testing set. RESULTS: Among the study
population, 1.2% (N=20,246) met the case definition for suicidal behavior. The
model achieved sensitive (33%-45% sensitivity), specific (90%-95% specificity),
and early (3-4 years in advance on average) prediction of patients' future
suicidal behavior. The strongest predictors identified by the model included both
well-known (e.g., substance abuse and psychiatric disorders) and less
conventional (e.g., certain injuries and chronic conditions) risk factors,
indicating that a data-driven approach can yield more comprehensive risk
profiles. CONCLUSIONS: Longitudinal EHR data, commonly available in clinical
settings, can be useful for predicting future risk of suicidal behavior. This
modeling approach could serve as an early warning system to help clinicians
identify high-risk patients for further screening. By analyzing the full
phenotypic breadth of the EHR, computerized risk screening approaches may enhance
prediction beyond what is feasible for individual clinicians.
PMID- 27609240
TI - Imaging Microglial Activation in Untreated First-Episode Psychosis: A PET Study
With [18F]FEPPA.
AB - OBJECTIVE: Neuroinflammation and abnormal immune responses are increasingly
implicated in the pathophysiology of schizophrenia. Previous positron emission
tomography (PET) studies targeting the translocator protein 18 kDa (TSPO) have
been limited by high nonspecific binding of the first-generation radioligand, low
resolution scanners, small sample sizes, and psychotic patients being on
antipsychotics or not being in the first episode of their illness. The present
study uses the novel second-generation TSPO PET radioligand [18F]FEPPA to
evaluate whether microglial activation is elevated in the dorsolateral prefrontal
cortex and hippocampus of untreated patients with first-episode psychosis.
METHOD: Nineteen untreated patients with first-episode psychosis (14 of them
antipsychotic naive) and 20 healthy volunteers underwent a high-resolution
[18F]FEPPA PET scan and MRI. Dynamic PET data were analyzed using the validated
two-tissue compartment model with arterial plasma input function with total
volume of distribution (VT) as outcome measure. All analyses were corrected for
TSPO rs6971 polymorphism (which is implicated in differential binding affinity).
RESULTS: No significant differences were observed between patients and healthy
volunteers in microglial activation, as indexed by [18F]FEPPA VT, in either the
dorsolateral prefrontal cortex or the hippocampus. There were no significant
correlations between [18F]FEPPA VT and duration of illness, clinical
presentation, or neuropsychological measures after adjusting for multiple
testing. CONCLUSIONS: The lack of significant differences in [18F]FEPPA VT
between groups suggests that microglial activation is not present in first
episode psychosis.
PMID- 27609242
TI - Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical
Trials.
AB - OBJECTIVE: Causes of placebo effects in antidepressant trials have been inferred
from observational studies and meta-analyses, but their mechanisms have not been
directly established. The goal of this study was to examine in a prospective,
randomized controlled trial whether patient expectancy mediates placebo effects
in antidepressant studies. METHOD: Adult outpatients with major depressive
disorder were randomly assigned to open or placebo-controlled citalopram
treatment. Following measurement of pre- and postrandomization expectancy,
participants were treated with citalopram or placebo for 8 weeks. Independent
samples t tests determined whether patient expectancy differed between the open
and placebo-controlled groups, and mixed-effects models assessed group effects on
Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for
treatment assignment. Finally, mediation analyses tested whether between-group
differences in patient expectancy mediated the group effect on HAM-D scores.
RESULTS: Postrandomization expectancy scores were significantly higher in the
open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group
(mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group
interaction, indicating that HAM-D scores for citalopram-treated participants
declined at a faster rate in the open group compared with the placebo-controlled
group. Patient expectations postrandomization partially mediated group effects on
week 8 HAM-D. CONCLUSIONS: Patient expectancy is a significant mediator of
placebo effects in antidepressant trials. Expectancy-related interventions should
be investigated as a means of controlling placebo responses in antidepressant
clinical trials and improving patient outcome in clinical treatment.
PMID- 27609243
TI - Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.
AB - OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and
Drug Administration (FDA) has mandated that warnings regarding suicide be
included in the prescribing information for hypnotic medications. The authors
conducted a review of the evidence for and against the claim that hypnotics
increase the risk of suicide. METHOD: This review focused on modern, FDA-approved
hypnotics, beginning with the introduction of benzodiazepines, limiting its
findings to adults. PubMed and Web of Science were searched, crossing the terms
"suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA
web site was searched for postmarketing safety reviews, and the FDA was contacted
with requests to provide detailed case reports for hypnotic-related suicide
deaths reported through its Adverse Event Reporting System. RESULTS:
Epidemiological studies show that hypnotics are associated with an increased risk
for suicide. However, none of these studies adequately controlled for depression
or other psychiatric disorders that may be linked with insomnia. Suicide deaths
have been reported from single-agent hypnotic overdoses. A separate concern is
that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in
rare cases may lead to suicidal ideation or suicidal behavior in persons who were
not known to be suicidal. On the other hand, ongoing research is testing whether
treatment of insomnia may reduce suicidality in adults with depression.
CONCLUSIONS: The review findings indicate that hypnotic medications are
associated with suicidal ideation. Future studies should be designed to assess
whether increases in suicidality result from CNS impairments from a given
hypnotic medication or whether such medication decreases suicidality because of
improvements in insomnia.
PMID- 27609244
TI - Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework.
AB - Tremendous progress has been made in basic neuroscience in recent decades. One
area that has been especially successful is research on how the brain detects and
responds to threats. Such studies have demonstrated comparable patterns of brain
behavior relationships underlying threat processing across a range of mammalian
species, including humans. This would seem to be an ideal body of information for
advancing our understanding of disorders in which altered threat processing is a
key factor, namely, fear and anxiety disorders. But research on threat processing
has not led to significant improvements in clinical practice. The authors propose
that in order to take advantage of this progress for clinical gain, a conceptual
reframing is needed. Key to this conceptual change is recognition of a
distinction between circuits underlying two classes of responses elicited by
threats: 1) behavioral responses and accompanying physiological changes in the
brain and body and 2) conscious feeling states reflected in self-reports of fear
and anxiety. This distinction leads to a "two systems" view of fear and anxiety.
The authors argue that failure to recognize and consistently emphasize this
distinction has impeded progress in understanding fear and anxiety disorders and
hindered attempts to develop more effective pharmaceutical and psychological
treatments. The two-system view suggests a new way forward.
PMID- 27609245
TI - Postpartum Psychosis: Madness, Mania, and Melancholia in Motherhood.
AB - OBJECTIVE: Psychosis or mania after childbirth is a psychiatric emergency with
risk for suicide and infanticide. METHOD: The authors reviewed the epidemiologic
and genetic research and physiological postpartum triggers (endocrine,
immunological, circadian) of psychosis. They also summarized all systematic
reviews and synthesized the sparse clinical studies to provide diagnostic
recommendations, treatment options, and strategies for prevention. RESULTS: The
incidence of first-lifetime onset postpartum psychosis/mania from population
based register studies of psychiatric admissions varies from 0.25 to 0.6 per
1,000 births. After an incipient episode, 20%-50% of women have isolated
postpartum psychosis. The remaining women have episodes outside the perinatal
period, usually within the bipolar spectrum. Presumably, the mechanism of onset
is related to physiological changes after birth (e.g., hormonal, immunological,
circadian), which precipitate disease in genetically vulnerable women. Some women
have treatable causes and comorbidities, such as autoimmune thyroiditis or
infections. N-methyl-d-aspartate-encephalitis or inborn errors of metabolism may
present after birth with psychosis. Fewer than 30 publications have focused on
the treatment of postpartum psychosis. The largest study (N=64) provided evidence
that lithium is highly efficacious for both acute and maintenance treatment.
Another report (N=34) described successful ECT treatment. Inpatient care is
usually required to ensure safety, complete the diagnostic evaluation, and
initiate treatment. The relapse risk after a subsequent pregnancy for women with
isolated postpartum psychoses is 31% (95% CI=22-42). Strategies for prevention of
postpartum psychosis include lithium prophylaxis immediately postpartum and
proactive safety monitoring. CONCLUSIONS: Postpartum psychosis offers an
intriguing model to explore etiologic contributions to the neurobiology of
affective psychosis.
PMID- 27609246
TI - Comparison of functional outcomes in elderly who have sustained a minor trauma
with or without head injury: a prospective multicenter cohort study.
AB - OBJECTIVES: The consequences of minor trauma involving a head injury (MT-HI) in
independent older adults are largely unknown. This study assessed the impact of a
head injury on the functional outcomes six months post-injury in older adults who
sustained a minor trauma. METHODS: This multicenter prospective cohort study in
eight sites included patients who were aged 65 years or older, previously
independent, presenting to the emergency department (ED) for a minor trauma, and
discharged within 48 hours. To assess the functional decline, we used a validated
test: the Older Americans' Resources and Services Scale. The cognitive function
of study patients was also evaluated. Finally, we explored the influence of a
concomitant injury on the functional decline in the MT-HI group. RESULTS: All 926
eligible patients were included in the analyses: 344 MT-HI patients and 582 minor
trauma without head injury. After six months, the functional decline was similar
in both groups: 10.8% and 11.9%, respectively (RR=0.79 [95% CI: 0.55-1.14]). The
proportion of patients with mild cognitive disabilities was also similar: 21.7%
and 22.8%, respectively (RR=0.91 [95% CI: 0.71-1.18]). Furthermore, for the group
of patients with a MT-HI, the functional outcome was not statistically different
with or without the presence of a co-injury (RR=1.35 [95% CI: 0.71-2.59]).
CONCLUSION: This study did not demonstrate that the occurrence of a MT-HI is
associated with a worse functional or cognitive prognosis than other minor
injuries without a head injury in an elderly population, six months after injury.
PMID- 27609247
TI - A Fully-Sealed Carbon-Nanotube Cold-Cathode Terahertz Gyrotron.
AB - Gigahertz to terahertz radiation sources based on cold-cathode vacuum electron
technology are pursued, because its unique characteristics of instant switch-on
and power saving are important to military and space applications. Gigahertz
gyrotron was reported using carbon nanotube (CNT) cold-cathode. It is reported
here in first time that a fully-sealed CNT cold-cathode 0.22 THz-gyrotron is
realized, typically with output power of 500 mW. To achieve this, we have studied
mechanisms responsible for CNTs growth on curved shape metal surface, field
emission from the sidewall of a CNT, and crystallized interface junction between
CNT and substrate material. We have obtained uniform growth of CNTs on and direct
growth from cone-cylinder stainless-steel electrode surface, and field emission
from both tips and sidewalls of CNTs. It is essential for the success of a CNT
terahertz gyrotron to have such high quality, high emitting performance CNTs.
Also, we have developed a magnetic injection electron gun using CNT cold-cathode
to exploit the advantages of such a conventional gun design, so that a large area
emitting surface is utilized to deliver large current for electron beam. The
results indicate that higher output power and higher radiation frequency
terahertz gyrotron may be made using CNT cold-cathode electron gun.
PMID- 27609248
TI - The role of amides in seminal cryopreservation of wild silverside, Odontesthes
bonariensis.
AB - Amides were tested as internal cryoprotectants for the preservation of wild
silverside (Odontesthes bonariensis) sperm. The semen was diluted in modified
Mounib's medium and cryopreserved by adding 2, 5, 8 or 11% of dimethyl acetamide
(DMA), dimethyl formamide (DMF) or methyl formamide (MF). Dimethyl sulfoxide
(DMSO) at a concentration of 10% diluted in modified Mounib's medium was used as
a control. The rate motility (17.7 +/- 1.9%) and time motility (143.2 +/- 9.7 s)
(P < 0.05) of the sperm were higher with 2% DMF when compared with the other
treatments. Despite the better motility results obtained with 2% DMF, the
solution was not able to maintain cellular structure integrity of the
cryopreserved sperm. The 10% DMSO and 8% MF treatment allowed for completeness of
the plasma membrane (34.8% and 29%), functional mitochondria (19.8% and 16.2%)
and plasma membrane fluidity (39.4% and 46.4%); furthermore, rate motility (11.8%
and 10%) and time motility (81.4 s and 71.8 s) of the sperm were found to be at
suitable levels when compared with 2% DMF. Thus, our evaluation suggests that 10%
DMSO and 8% MF provide better cryopreservation of O. bonariensis sperm cells.
PMID- 27609241
TI - Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide
Meta- and Mega-Analysis.
AB - OBJECTIVE: Structural brain imaging studies in obsessive-compulsive disorder
(OCD) have produced inconsistent findings. This may be partially due to limited
statistical power from relatively small samples and clinical heterogeneity
related to variation in illness profile and developmental stage. To address these
limitations, the authors conducted meta- and mega-analyses of data from OCD sites
worldwide. METHOD: T1 images from 1,830 OCD patients and 1,759 control subjects
were analyzed, using coordinated and standardized processing, to identify
subcortical brain volumes that differ between OCD patients and healthy subjects.
The authors performed a meta-analysis on the mean of the left and right
hemisphere measures of each subcortical structure, and they performed a mega
analysis by pooling these volumetric measurements from each site. The authors
additionally examined potential modulating effects of clinical characteristics on
morphological differences in OCD patients. RESULTS: The meta-analysis indicated
that adult patients had significantly smaller hippocampal volumes (Cohen's d=
0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16)
compared with adult controls. Both effects were stronger in medicated patients
compared with controls (d=-0.29, % difference=-4.18, and d=0.29, %
difference=4.38, respectively). Unmedicated pediatric patients had significantly
larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric
controls. None of these findings were mediated by sample characteristics, such as
mean age or scanning field strength. The mega-analysis yielded similar results.
CONCLUSIONS: The results indicate different patterns of subcortical abnormalities
in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of
importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD.
These findings highlight the potential importance of neurodevelopmental
alterations in OCD and suggest that further research on neuroplasticity in OCD
may be useful.
PMID- 27609249
TI - Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices
Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System.
AB - OBJECTIVES: This study aims to describe the discussions and recommendations made
during the U.S. Food and Drug Administration (FDA) Circulatory System Device
Panel pre-market approval application for the Absorb Bioresorbable Vascular
Scaffold (BVS) System. BACKGROUND: The Absorb BVS System is a first-of-its-kind
fully bioresorbable percutaneous coronary intervention technology. The absorb BVS
was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the
Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects
with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S.
investigational device exemption trial. METHODS: Observational report of the FDA
Circulatory System Device Panel pre-market approval application meeting held on
March 15, 2016. RESULTS: The U.S. FDA Circulatory System Device Panel members
reviewed the ABSROB III trial outcomes and additional post hoc analyses presented
by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of
noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting
stent, for target lesion failure at 1 year. Although a higher numerical trend for
adverse outcomes was reported for the Absorb BVS, there were no statistical
differences between Absorb BVS and XIENCE for any safety or effectiveness
components for target lesion failure or for the secondary pre-specified outcomes.
Panel members raised concerns with regard to the ABSORB III results and post hoc
analyses focusing mainly on the noninferiority design of the trial, the apparent
safety issues of the Absorb BVS in small vessels, the mismatch of visually versus
intravascular imaging assessed vessel size found in ABSORB III and its
implications on the adequate device labeling, the safety of Absorb BVS in
specific patient and lesion subsets, and the post-approval commitments of the
sponsor. CONCLUSIONS: Following panel discussions and the evidence presented, the
panel voted for approval of the device.
PMID- 27609250
TI - Survival After Varying Revascularization Strategies in Patients With ST-Segment
Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: A
Pairwise and Network Meta-Analysis.
AB - OBJECTIVES: The authors conducted a systematic pairwise and network meta-analysis
to assess optimal treatment strategies in patients with ST-segment elevation
myocardial infarction (STEMI) and multivessel coronary artery disease (MV-CAD)
undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Patients
with STEMI and MV-CAD have a worse prognosis than those with single-vessel CAD.
The optimal revascularization strategy for these patients is uncertain. METHODS:
Studies of revascularization strategies for MV-CAD in STEMI patients undergoing
primary PCI published between 2001 and 2015 were identified using an electronic
search. Pairwise and network meta-analyses were performed for 3 PCI strategies in
prospective and retrospective studies: 1) infarct-related artery (IRA)-only PCI;
2) single procedure MV-PCI; and 3) staged MV-PCI. Information on study design,
inclusion and exclusion criteria, and clinical outcomes was extracted. The
outcomes of interest were short-term and long-term mortality. RESULTS: Thirty-two
studies (13 prospective and 19 retrospective) with 54,148 patients (IRA-only PCI
[n = 42,112], single procedure MV-PCI [n = 8,138], and staged MV-PCI [n = 3,898])
were included in the analysis. Pairwise meta-analyses showed that staged MV-PCI
was associated with lower short-term and long-term mortality compared with both
IRA-only PCI and single stage MV-PCI, whereas IRA-only PCI was associated with
lower mortality compared with single stage MV-PCI. Staged MV-PCI was also
associated consistently with improved survival in network analyses. CONCLUSIONS:
The present systematic review and meta-analysis supports the hypothesis that in
patients with MV-CAD presenting with STEMI undergoing primary PCI, a staged
multivessel revascularization strategy may improve early and late survival.
PMID- 27609251
TI - Percutaneous Coronary Intervention for Multivessel Disease and ST-Segment
Elevation Myocardial Infarction: When, Not Whether.
PMID- 27609252
TI - Impact of Chronic Total Occlusion of the Coronary Artery on Long-Term Prognosis
in Patients With Ischemic Systolic Heart Failure: Insights From the COMMIT-HF
Registry.
AB - OBJECTIVES: This study sought to assess the impact of chronic total occlusion
(CTO) on long-term prognosis in patients with ischemic cardiomyopathy.
BACKGROUND: The presence of concomitant CTO in a nonculprit lesion in acute
coronary syndromes is associated with worse prognosis. Coronary artery disease is
the main cause of heart failure and in many cases at least 1 CTO is observed.
METHODS: The study included all patients with systolic heart failure who
underwent elective coronary angiography and were registered from January 2009 to
December 2014 in the ongoing single-center COMMIT-HF (COnteMporary Modalities In
Treatment of Heart Failure) registry (NCT02536443). The patients were divided
into 2 groups with regard to CTO presence. All of the analyzed patients were
followed up for at least 12 months with all-cause mortality defined as the
primary endpoint. RESULTS: Of the 675 patients fulfilling the inclusion and
exclusion criteria, 278 patients (41.2%) had 1 or more CTOs of a major coronary
artery (+CTO), and in 397 patients (58.8%) the presence of the CTO was not
observed (-CTO). The 12-month mortality for the +CTO and -CTO patients was 19.4 %
and 10.3 %, respectively (p < 0.001), evident also after 24 months (26.6% vs.
17.6%; p = 0.01). After a multivariate adjustment for differences in baseline
characteristics, the presence of CTO remained significantly associated with
higher 12-month mortality (relative risk: 1.84: 95% confidence interval: 1.18 to
2.85; p = 0.006). CONCLUSIONS: Our analysis showed that in patients with ischemic
heart failure the presence of the CTO is related to worse long-term prognosis.
PMID- 27609253
TI - Ischemic Cardiomyopathy and Chronic Total Occlusions: Poor Prognosis, Worse in
Combination.
PMID- 27609255
TI - Stuck Between a Clot and a Cold Place: The Specter of Early In-Stent Thrombosis
With Therapeutic Hypothermia.
PMID- 27609254
TI - Therapeutic Hypothermia and Stent Thrombosis: A Nationwide Analysis.
AB - OBJECTIVES: This study sought to determine whether "real-world" data supported
the hypothesis that therapeutic hypothermia (TH) led to increased rates of stent
thrombosis. BACKGROUND: TH, which is often instituted after cardiac arrest (CA)
to improve neurologic outcomes, alters pharmacokinetics of antiplatelet
medications, leading to a theoretical risk of stent thrombosis after percutaneous
coronary intervention (PCI). METHODS: CA patients with acute myocardial
infarction undergoing PCI were identified from the Nationwide Inpatient Sample
from 2006 to 2011, with a defined primary outcome of stent thrombosis. The
incidence of stent thrombosis in patients undergoing TH versus those not
undergoing TH was compared using both logistic regression and propensity score
matching. RESULTS: In this dataset, 49,109 CA patients underwent PCI for acute
myocardial infarction from 2006 to 2011, of whom 1,193 (2.4%) underwent TH. The
incidence of stent thrombosis in the TH group was 3.9% (43 of 1,193), compared to
4.7% (2,271 of 47,916) in the no TH group (p = 0.61). Logistic regression showed
that TH was not a significant predictor of stent thrombosis with an adjusted odds
ratio of 0.71 (95% confidence interval: 0.28 to 1.76; p = 0.46). Propensity
matching was performed to adjust for baseline differences between the TH and no
TH groups, matching 1,155 patients in the TH group with 3,399 patients in the no
TH group. No difference was observed in the incidence of stent thrombosis in the
TH and the no TH groups after propensity matching (3.5% vs. 6.1%; p = 0.17).
CONCLUSIONS: TH does not increase the incidence of stent thrombosis after primary
PCI in patients with acute myocardial infarction presenting as CA.
PMID- 27609257
TI - The Future of Transaortic Transcatheter Aortic Valve Replacement.
PMID- 27609256
TI - Transcatheter Aortic Valve Replacement Using Transaortic Access: Experience From
the Multicenter, Multinational, Prospective ROUTE Registry.
AB - OBJECTIVES: The Registry of the Utilization of the TAo-TAVR approach using the
Edwards SAPIEN Valve (ROUTE) was established to assess the effectiveness and
safety of the use of transaortic (TAo) access for transcatheter aortic valve
replacement (TAVR) procedures (NCT01991431). BACKGROUND: TAVR represents an
alternative to surgical valve replacement in high-risk patients. Whereas the
transfemoral access route is used commonly as the first-line approach,
transapical access is an option for patients not suitable for transfemoral
treatment mainly due to anatomic conditions. TAo-TAVR has been shown to be a
viable alternative surgical access route; however, only limited data on its
effectiveness and safety has been published. METHODS: ROUTE is a multicenter,
international, prospective, observational registry; data were collected from 18
centers across Europe starting in February 2013. Patients having severe calcific
aortic stenosis were documented if they were scheduled to undergo TAo-TAVR using
an Edwards SAPIEN XT or a SAPIEN 3 valve. The primary endpoint was 30-day
mortality. Secondary endpoints were intraprocedural or in hospital and 30-day
complication rates. RESULTS: A total of 301 patients with a mean age of 81.7 +/-
5.9 years and an Society of Thoracic Surgeons score of 9.0 +/- 7.6% were
included. Valve success was documented in 96.7%. The 30-day mortality was 6.1%
(18/293) (procedure-related mortality: 3.1%; 9 of 293). The Valve Academic
Research Consortium-2 defined complications included myocardial infarction
(1.0%), stroke (1.0%), transient ischemic attack (0.3%), major vascular
complications (3.4%), life-threatening bleeding (3.4%), and acute kidney injury
(9.5%). In 3.3% of patients, paravalvular regurgitation was classified as
moderate or severe (10 of 300). Twenty-six patients (8.8%) required permanent
pacemaker implantation. CONCLUSIONS: TAo access for TAVR seems to be a safe
alternative to the transapical procedure.
PMID- 27609258
TI - Predictors for Successful Endovascular Intervention in Chronic Carotid Artery
Total Occlusion.
AB - OBJECTIVES: This study sought to determine predictors for successful endovascular
treatment in patients with chronic carotid artery occlusion (CAO). BACKGROUND:
Endovascular recanalization in patients with chronic CAO has been reported to be
feasible, but technically challenging. METHODS: Endovascular attempts in 138
consecutive chronic CAO patients with impaired ipsilateral hemisphere perfusion
were reviewed. We analyzed potential variables including epidemiology,
symptomatology, angiographic morphology, and interventional techniques in
relation to the technical success. RESULTS: The technical success rate was 61.6%.
Multivariate analysis showed absence of prior neurologic event (odds ratio [OR]:
0.27; 95% confidence interval [CI]: 0.10 to 0.76), nontapered stump (OR: 0.18;
95% CI: 0.05 to 0.67), distal internal carotid artery (ICA) reconstitution via
contralateral injection (OR: 0.19; 95% CI: 0.05 to 0.75), and distal ICA
reconstitution at communicating or ophthalmic segments (OR:0.12; 95% CI: 0.04 to
0.36) to be independent factors associated with lower technical success. Point
scores were assigned proportional to model coefficients, and technical success
rates were >80% and <40% in patients with scores of <=1 and >=4, respectively.
The c-indexes for this score system in predicting technical success was 0.820
(95% CI: 0.748 to 0.892; p < 0.001) with a sensitivity of 84.7% and a specificity
of 67.9%. CONCLUSIONS: Absence of prior neurologic event, nontapered stump,
distal ICA reconstitution via contralateral injection, and distal ICA
reconstitution at communicating or ophthalmic segments were identified as
independent negative predictors for technical success in endovascular
recanalization for CAO.
PMID- 27609259
TI - Endovascular Intervention in Chronic Total Carotid Artery Occlusion: It Can be
Done, But When Should it be Done?
PMID- 27609261
TI - Percutaneous Device Closure of a Post-Traumatic Ventricular Septal Rupture.
PMID- 27609260
TI - Intentional Laceration of the Anterior Mitral Valve Leaflet to Prevent Left
Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve
Replacement: Pre-Clinical Findings.
AB - OBJECTIVES: The authors propose a novel transcatheter transection of the anterior
mitral leaflet to prevent iatrogenic left ventricular outflow tract (LVOT)
obstruction during transcatheter mitral valve replacement (TMVR). BACKGROUND:
LVOT obstruction is a life-threatening complication of TMVR caused by septal
displacement of the anterior mitral leaflet. METHODS: In vivo procedures in swine
were guided by biplane x-ray fluoroscopy and intracardiac echocardiography.
Retrograde transaortic 6-F guiding catheters straddled the anterior mitral
leaflet. A stiff 0.014-inch guidewire with polymer jacket insulation was
electrified and advanced from the LVOT, through the A2 leaflet base, into the
left atrium. The wire was snared and externalized, forming a loop that was
energized and withdrawn to lacerate the anterior mitral leaflet. RESULTS: The
anterior mitral leaflet was successfully lacerated in 7 live and 1 post-mortem
swine under heparinization. Lacerations extended to 89 +/- 19% of leaflet length
and were located within 0.5 +/- 0.4 mm of leaflet centerline. The chordae were
preserved and retracted the leaflet halves away from the LVOT. LVOT narrowing
after benchtop TMVR was significantly reduced with intentional laceration of the
anterior mitral leaflet to prevent LVOT obstruction than without (65 +/- 10% vs.
31 +/- 18% of pre-implantation diameter, p < 0.01). The technique caused mean
blood pressure to fall (from 54 +/- 6 mm Hg to 30 +/- 4 mm Hg, p < 0.01), but
blood pressure remained steady until planned euthanasia. No collateral tissue
injury was identified on necropsy. CONCLUSIONS: Using simple catheter techniques,
the anterior mitral valve leaflet was transected. Cautiously applied in patients,
this strategy can prevent anterior mitral leaflet displacement and LVOT
obstruction caused by TMVR.
PMID- 27609262
TI - Catheter-Induced Iatrogenic Coronary Artery Dissection in Patients With
Spontaneous Coronary Artery Dissection.
PMID- 27609263
TI - T-Stenting With Small Protrusion: The Default Strategy for Bailout Provisional
Stenting?
PMID- 27609264
TI - State of Structural and Congenital Heart Disease Interventional Training in
United States and Canada: An Assessment by the American College of Cardiology
Fellows-in-Training Section Leadership Council.
PMID- 27609266
TI - Smoke Screen.
PMID- 27609265
TI - Bioresorbable Scaffolds: What Does "Less Forgiving" Mean?
PMID- 27609267
TI - Kawasaki disease associated with Mycoplasma pneumoniae.
AB - BACKGROUND: Kawasaki disease (KD) is an illness of unknown etiology that mostly
occurs in children under 5 years of age and is the leading cause of acquired
heart disease all over the world. Mycoplasma pneumoniae (MP) was one of the
likely causative agents of KD. However, the etiologic effect of MP in KD has not
been fully recognized. METHODS: We prospectively analyzed the clinical records of
450 patients with KD hospitalized in Children's Hospital of Soochow University
from 2012 to 2014. Using medical records, we retrospectively identified patients
with low respiratory tract infection (non-KD group). RESULTS: Of the 450 KD
patients, MP was positive in 62 (13.8 %). The median age of the MP + KD+ group
was significantly older than the MP-KD+ group (25 vs 14.5 months, P < 0.01). MP +
KD+ group had higher levels of ESR, N% and CRP than the MP-KD+ group. MP + KD+
group were more frequent in respiratory disorders than MP-KD+ group with a P <
0.05. No statistical difference of non-responders or coronary artery lesion was
found between the groups. CONCLUSIONS: MP infections are found in an important
proportion of the KD patients (13.8 % in our series). MP infection tended to
occur in older populations and with a higher rate of respiratory tract
involvement in patients with KD. No statistical difference of non-responders or
coronary artery lesion was found between the MP+ and MP- KD patients.
PMID- 27609268
TI - Depression-like behaviors and heme oxygenase-1 are regulated by Lycopene in
lipopolysaccharide-induced neuroinflammation.
AB - Previous studies have demonstrated that lycopene possesses anti-inflammatory
properties in the central nervous system. However, the potential role and the
molecular mechanisms of lycopene in lipopolysaccharide (LPS)-challenge
inflammation and depression-like behaviors has not been clearly investigated. The
present study aimed to assess the effects and the potential mechanisms of
lycopene on LPS-induced depression-like behaviors. Lycopene was orally
administered (60mg/kg) every day for seven days followed by intraperitoneal LPS
injection (1mg/kg). The Forced swim test and tail suspension test were used to
detect changes in the depression-like behaviors. ELISA was used to measure the
expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha(TNF-alpha) in
the plasma. Immunoblotting was performed to measure the expression of interleukin
1beta (IL-1beta) and heme oxygenase-1 (HO-1) in the hippocampus. The results
showed that pretreatment with lycopene could ameliorate depression-like
behaviors. Moreover, lycopene relieved neuronal cell injury in hippocampal CA1
regions. Furthermore, lycopene decreased LPS-induced expression of IL-1beta and
HO-1 in the hippocampus together with decreasing level of IL-6 and TNF-alpha in
the plasma. Taken together, these results suggest that lycopene can attenuate LPS
induced inflammation and depression-like behaviors, which may be involved in
regulating HO-1 in the hippocampus.
PMID- 27609270
TI - Sudden hearing loss as the initial symptom in Japanese patients with multiple
sclerosis and seropositive neuromyelitis optica spectrum disorders.
AB - Sudden hearing loss may occur in rare cases of relapsing-remitting multiple
sclerosis (RRMS). There have also been reports of idiopathic sudden sensorineural
hearing loss (SNHL) in patients with neuromyelitis optica spectrum disorders
(NMOSD), but the frequency of such cases is unclear. We conducted a retrospective
analysis of the medical records of 173 consecutive patients with multiple
sclerosis (MS) and 101 consecutive patients with NMOSD who tested positive for
anti-aquaporin-4 antibodies in addition to 37 consecutive patients with
clinically isolated syndromes (CIS) to investigate the frequency and onset timing
of SNHL. SNHL was observed in six (3.5%) of the RRMS cases, one (1.0%) of the
seropositive NMOSD cases, and three (8.1%) of the CIS cases. SNHL occurred ahead
of onset in 4/6 MS patients and in all of 3 CIS patients. Patient with NMOSD
exhibited SNHL 6years after the onset of NMOSD. Although SNHL is rare, these
results suggest the risk of developing demyelinating lesions in the central
nervous system and further conversion to MS in the future.
PMID- 27609269
TI - The immunomodulatory effect of laquinimod in CNS autoimmunity is mediated by the
aryl hydrocarbon receptor.
AB - Though several functional properties of laquinimod have been identified, our
understanding of the underlying mechanisms is still incomplete. Since the
compound elicits similar immunomodulatory effects to ligands of the aryl
hydrocarbon receptor (AhR), we compared the efficacy of laquinimod in
experimental autoimmune encephalomyelitis (EAE)-afflicted wild-type and AhR
deficient mice. Laquinimod failed to ameliorate clinical symptoms and leukocyte
infiltration in AhR-deficient mice; however, treatment exerted neuroprotection by
elevation of brain-derived neurotrophic factor (BDNF) independent of genetic
profile. Thus, our data identify the AhR pathway in these mutant mice as crucial
for the immunomodulatory, but not neuroprotective, efficacy of laquinimod in EAE.
PMID- 27609271
TI - Anti-hsp60 antibody responses based on Helicobacter pylori in patients with
multiple sclerosis: (ir)Relevance to disease pathogenesis.
AB - In view of published data suggesting that Helicobacter pylori (Hp) is a trigger
of multiple sclerosis (MS), we assessed anti-heat shock protein 60 (hsp60)Hp
antibody reactivity in 129 MS patients and 48 demograpically-matched healthy
controls (HCs). Anti-Hp antibodies by ELISA were more elevated in MS than HCs but
did not differ between different MS phenotypes. All anti-Hp-positive MS sera,
irrespectively of their clinical phenotype, were anti-anti-hsp60 positive. Anti
hsp60 Hp seropositivity correlated with age at disease onset. In conclusion, anti
hsp60 Hp antibodies are present in all anti-Hp positive MS patients, and their
relevance to disease pathogenesis is questionable.
PMID- 27609272
TI - Fingolimod suppresses bone resorption in female patients with multiple sclerosis.
AB - Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the
inflammatory activity of multiple sclerosis (MS), and has been shown to suppress
osteoporosis in mouse models. In this study, levels of bone turnover markers were
quantified in serum and urine samples from MS patients treated with fingolimod.
Compared with untreated MS patients and healthy controls, fingolimod-treated MS
patients had a significantly lower level of the bone resorption marker type I
collagen cross-linked N-telopeptide in urine. This finding was prominent in
female but was not seen in male subjects. Our results suggest that fingolimod may
have a beneficial effect on bone mass loss in female MS patients.
PMID- 27609273
TI - Microglia response in retina and optic nerve in chronic experimental autoimmune
encephalomyelitis.
AB - Experimental autoimmune encephalomyelitis (EAE) is a common rodent model for
multiple sclerosis (MS). Yet, the long-term consequences for retina and optic
nerve (ON) are unknown. C57BL/6 mice were immunized with an encephalitogenic
peptide (MOG35-55) and the controls received the carriers or PBS. Clinical
symptoms started at day 8, peaked at day 14, and were prevalent until day 60.
They correlated with infiltration and demyelination of the ON. In MOG-immunized
animals more microglia cells in the ONs and retinas were detected at day 60.
Additionally, retinal ganglion cell (RGC) loss was combined with an increased
macroglia response. At this late stage, an increased number of microglia was
associated with axonal damage in the ON and in the retina with RGC loss. Whether
glial activation contributes to repair mechanisms or adversely affects the number
of RGCs is currently unclear.
PMID- 27609274
TI - Genetic background modulates outcome of therapeutic amyloid peptides in treatment
of neuroinflammation.
AB - Amyloid hexapeptide molecules are effective in the treatment of the murine model
of neuroinflammation, known as experimental autoimmune encephalomyelitis (EAE).
Efficacy however differs between two inbred mouse strains, C57BL/6J (B6) and
C57BL/10SnJ (B10). Amyloid hexapeptide treatments improved the clinical outcomes
of B6, but not B10 mice, indicating that genetic background influences
therapeutic efficacy. Moreover, although previous studies indicated that prion
protein deficiency results in more severe EAE in B6 mice, we observed no such
effect in B10 mice. In addition, we found that amyloid hexapeptide treatments of
B10 and B6 mice elicited differential IL4 responses. Thus, the modulatory
potential of prion protein and related treatments with other amyloid hexapeptides
in EAE depends on mouse strain.
PMID- 27609276
TI - Thymus involvement in myasthenia gravis: Epidemiological and clinical impacts of
different self-tolerance breakdown mechanisms.
AB - The reasons for the abrogation of self-immunological tolerance in patients with
myasthenia gravis (MG) may be different between those with concomitant thymic
hyperplasia or thymoma, and those with no evidence of thymic involvement. We
conducted a retrospective observational case series study to investigate the
epidemiology as well as the clinical, serologic, and electromyographic (EMG)
characteristics of individuals diagnosed as having MG. We found that the average
age at MG onset of patients with either thymic hyperplasia or thymoma was much
younger (by ~20years) than that of MG patients without thymic involvement. Thymic
hyperplasia was more common in females than males. There were no differences in
the rates of ocular MG vs. generalized MG among those three study groups. There
were also no group differences in the rates of neuromuscular junction
disfunction, as observed on EMG or by the results of serology tests for acetyl
choline receptor antibody. Interestingly, only patients without thymic
involvement had other autoimmune diseases, and most of them were females. The
patients with other coexisting autoimmune disease had a similar age at MG onset
as the other patients with no thymic involvement. These results shed light on the
impact of epidemiological and clinical factors that result from different
mechanisms of self-immunological tolerance breakdown that occurs in MG.
PMID- 27609275
TI - Autoantibody profile and clinical characteristics in a cohort of Chinese adult
myasthenia gravis patients.
AB - Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies
against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and
ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The
AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8%
of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma
MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR
antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in
late onset patients (54.4% and 33.3%, respectively). These two antibodies may
indicate an underlying thymoma when combined. The patients with titin and RyR
antibodies tend to have more severe disease and worse outcome, and may need more
active immunosuppressive treatment.
PMID- 27609277
TI - The role of AQP4 in neuromyelitis optica: More answers, more questions.
AB - Neuromyelitis optica (NMO) is a recurrent inflammatory disease that
preferentially targets the optic nerves and spinal cord. The presence of
antibodies to the water channel protein aquaporin-4 (AQP4), expressed almost
exclusively in astrocytes in the central nervous system (CNS), is a reliable
biomarker for NMO. These antibodies, NMO-IgG, may be responsible for the
sequential cascade of immune events, including IgG/IgM deposition, infiltration
of granulocytes and complement-mediated cytotoxicity (i.e. astrocyte loss) and
demyelination. This review summarizes current thinking about the role of NMO-IgG
in the pathogenesis of this condition. New insights were also generated along
with important additional questions.
PMID- 27609278
TI - Immunological studies of cerebrospinal fluid from patients with CNS symptoms
after human papillomavirus vaccination.
AB - In 32 patients with prolonged central nervous system symptoms after human
papillomavirus (HPV) vaccination, we measured conventional and immunological
markers in cerebrospinal fluid (CSF) and compared with the levels in disease
controls. Our studies revealed significantly decreased chloride and neuron
specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV
vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells
increased significantly in patients, and IL-17 increased significantly from 12 to
24months after symptom onset. Chemokines (IL-8 and MCP-1) were also elevated, but
CD8(+) T cells, PDGF-bb and IL-12 were reduced. Antibodies to GluN2B-NT2, GluN2B
CT and GluN1-NT increased significantly. These results suggest biological, mainly
immunological, changes in the CSF of patients after HPV vaccination.
PMID- 27609279
TI - Therapeutic target of memory B cells depletion helps to tailor administration
frequency of rituximab in myasthenia gravis.
AB - Rituximab (RTX) has demonstrated efficacy in limiting relapses in myasthenia
gravis (MG). We investigated the interest of CD27+ memory B cell monitoring in
patients as a biological marker of clinical relapse. Twenty-four patients have
been treated with RTX (375mg/m(2)/week-month as an induction treatment).
Maintenance treatment consisted with either systematic treatment every 3months or
only when CD27+ memory B cells were detectable. After the induction treatment,
the mean infusions were 1.3/year compared with 4/year. We suggest that RTX
administration frequency can be decreased safely by monitoring the re-emerging
CD27+ memory B cells.
PMID- 27609280
TI - Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative
biomarkers for the early onset and progression of multiple sclerosis.
AB - Clinically isolated syndrome (CIS) is a first, usually recovering, episode of
neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects
might benefit from early disease-modifying drugs, provided that those at high
risk of developing MS can be identified. Gene expression for dopaminergic
receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS
patients and is affected by treatment with interferon (IFN)-beta. In particular,
lymphocyte DR D5 mRNA might be a marker of IFN-beta response in MS patients. No
information exists so far in CIS subjects. We investigated DR and AR gene
expression in peripheral blood mononuclear cells (PBMC) and in CD4+ T effector
(Teff) and regulatory (Treg) cells from CIS subjects, and assessed their
relationship with MS progression after 12months. Expression of several DR and AR
are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and alpha2A-AR
mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12months.
Results show the involvement of dopaminergic and adrenergic pathways in CIS as
well as in MS pathogenesis, supporting the evaluation of dopaminergic and
adrenergic agents in MS.
PMID- 27609281
TI - Neuron-astrocyte interactions in spinal cord dorsal horn in neuropathic pain
development and docosahexaenoic acid therapy.
AB - The analgesic activity of docosahexaenoic acid (DHA, 22:6 n-3) was studied using
a chronic constriction injury (CCI) rat model. Animals were subcutaneously
injected with DHA emulsion at a dose of 4.5mg/kg (125mM/kg) daily during 2weeks
after surgery. We characterized the dynamics of GFAP-positive astrocyte,
substance P (SP) and nNOS-positive neurons activity in the spinal cord dorsal
horn (SCDH) superficial lamina. We found that DHA treatment decrease the
intensity and duration of neurogenic pain syndrome, results in earlier
stabilization of weight distribution, prevents the cold allodynia and dystrophic
changings in denervated limb tissue. DHA treatment reduced the reactive astrocyte
number, decrease SP-immunopositive fibers and nNOS-positive neurons number in the
SCDH in neuropathic pain.
PMID- 27609282
TI - The contribution of the sympathetic nervous system to the immunopathology of
experimental pulmonary tuberculosis.
AB - The role of norepinephrine (NE) in the immunopathology of experimental
tuberculosis (TB) was studied by measuring pulmonary NE and determining its
cellular sources and targets. Functional studies were performed administrating
adrenergic and anti-adrenergic drugs at different TB phases. Results showed high
production of NE during early infection by adrenergic nerve terminals and
lymphocytes located in the lungs and mediastinal lymph nodes, these cells highly
expressed beta2 adreno-receptors (beta2AR) which by an autocrine mechanism
promote Th-1 cell differentiation favoring protection. During advanced infection,
the production of NE and beta2AR sharply decreased, suggesting that adrenergic
activity is less important during late TB.
PMID- 27609283
TI - Capparis ovata treatment suppresses inflammatory cytokine expression and
ameliorates experimental allergic encephalomyelitis model of multiple sclerosis
in C57BL/6 mice.
AB - Since ancient times, Capparis species have been widely used in traditional
medicine to treat various diseases. Our recent investigations have suggested
Capparis ovata's potential anti-neuroinflammatory application for the treatment
of multiple sclerosis (MS). The present study was designed to precisely determine
the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of
MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and
flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female
C57BL/6J mice with MOG35-55/CFA. COWE was administered at a daily dose of
500mg/kg by oral gavage either from the day of immunization (T1) or at disease
onset (T2) for 21days. Gene expression analysis was performed using a Mouse
Multiple Sclerosis RT2 Profiler PCR Array, and further determinations and
validations of the identified genes were performed using qPCR. Whole-genome
transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K
microarrays. Immunohistochemical staining was applied to brain sections of the
control and treated mice to examine the degree of degeneration. COWE was further
fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple
Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in
T1, and the disease activity was completely inhibited. In the T2 group, the
maximal score was significantly reduced compared with that of the parallel EAE
group. The COWE suppression of EAE was associated with a significantly decreased
expression of genes that are important in inflammatory signaling, such as
TNFalpha, IL6, NF-kappaB, CCL5, CXCL9, and CXCK10. On the other hand, the
expression of genes involved in myelination/remyelination was significantly
increased. Immunohistochemical analysis further supported these effects, showing
that the number of infiltrating immune cells was decreased in the brains of COWE
treated animals. In addition, differential expression profiling of the
transcriptome revealed that COWE treatment caused the down regulation of a group
of genes involved in the immune response, inflammatory response, antigen
processing and presentation, B-cell-mediated immunity and innate immune response.
Collectively, these results suggest anti-neuroinflammatory mechanisms by which
COWE treatment delayed and suppressed the development of EAE and ameliorated the
disease in mice with persistent clinical signs.
PMID- 27609284
TI - Complimentary action: C1q increases ganglion cell survival in an in vitro model
of retinal degeneration.
AB - Using a previously described retinal explant culture system as an acute injury
model, we here explore the role of C1q, the initiator of the classical complement
pathway, in neuronal cell survival and retinal homeostasis. Full-thickness adult
rat retinal explants were divided into four groups, receiving the following
supplementation: C1q (50nM), C1-inhibitor (C1-inh; Berinert; 500mg/l), C1q+C1
inh, and no supplementation (culture controls). Explants were kept for 12h or
2days after which they were examined morphologically and with a panel of
immunohistochemical markers. C1q supplementation protects ganglion cells from
degeneration within the explant in vitro system. This effect is correlated to an
attenuated endogenous production of C1q, and a quiesced gliotic response.
PMID- 27609285
TI - Miller Fisher syndrome presenting as palate paralysis.
AB - We report a 63-year old patient who presented to our care initially with a
hypernasal voice followed by ataxia, ptosis, dysphonia, and paresthesias. The
patient's history, physical examination, and additional tests led to a Miller
Fisher syndrome (MFS) diagnosis. Palatal paralysis as an inaugurating
manifestation of MFS is quite rare and requires special attention from
neurologists and otolaryngologists. Although it may present as benign as an acute
change in voice, early diagnosis and prompt management may prevent further
complications.
PMID- 27609286
TI - Changes in endothelial cell proliferation and vascular permeability after
systemic lipopolysaccharide administration in the subfornical organ.
AB - The subfornical organ (SFO) has highly permeable fenestrated vasculature and is a
key site for immune-to-brain communications. Recently, we showed the occurrence
of continuous angiogenesis in the SFO. In the present study, we found that
systemic administration of bacterial lipopolysaccharide (LPS) reduced the
vascular permeability and endothelial cell proliferation. In LPS-administered
mice, the SFO vasculature showed a significant decrease in the immunoreactivity
of plasmalemma vesicle associated protein-1, a marker of endothelial fenestral
diaphragms. These data suggest that vasculature undergoes structural change to
decrease vascular permeability in response to systemic LPS administration.
PMID- 27609287
TI - Astilbin ameliorates experimental autoimmune myasthenia gravis by decreased Th17
cytokines and up-regulated T regulatory cells.
AB - Astilbin, a major bioactive compound extracted from Rhizoma smilacis glabrae
(RSG), has been reported to possess immunosuppressive properties. Our study first
evaluated the effect of astilbin on experimental autoimmune myasthenia gravis
(EAMG) in Lewis rats. The results showed that astilbin could attenuate the
severity of EAMG by decreasing antigen-specific autoantibodies with up-regulation
of regulatory T cells and down-regulation of Th17 cells. In addition to, astilbin
also reduced the efficiency of the antigen presenting cells on which the
expression of MHC class II decreased. These results suggest that astilbin might
be a candidate drug for immunoregulation of EAMG, and provide us new treatment
ideas for human myasthenia gravis (MG).
PMID- 27609288
TI - The role of IL-1beta and glutamate in the effects of lipopolysaccharide on the
hippocampal electrical kindling of seizures.
AB - In our study, we used rapid electrical hippocampal kindling and in vivo
microdialysis methods to assess the involvement of inflammatory mediators:
lipopolysaccharide (LPS) and proinflammatory interleukin-1beta (IL-1beta) in
mechanisms of epileptogenesis. We observed, that both, LPS and IL-1beta,
administered into stimulated hippocampus, accelerated kindling process. LPS also
increased the expression of IL-1beta in stimulated hippocampus in kindled rats.
In vivo acute LPS perfusion, via a microdialysis cannula implanted into the naive
rat's hippocampus, produced an increase in extracellular glutamate release. We
suppose, that particularly IL-1beta action and increased glutamate concentration
may significantly contribute to LPS effects on kindling development.
PMID- 27609289
TI - Increased expression of interleukin 17 in the cortex and hippocampus from
patients with mesial temporal lobe epilepsy.
AB - Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsies
in adults and proinflammatory cytokines have long been thought to play an
important role in pathogenesis and epileptogenicity. In the present study, we
investigated the levels and expression patterns of the interleukin 17 (IL-17)
system in temporal neocortex and hippocampus from 24 patients with MTLE and 8
control (Ctr) samples. We found that IL-17 and IL-17 receptor (IL-17R) were
clearly upregulated in MTLE at both mRNA and protein levels, compared with Ctr.
Immunostaining indicated that neurons, astrocytes, microglia and endothelial
cells of blood vessels are the major sources of IL-17. These findings suggest
that IL-17 system may be involved in the pathogenesis and epileptogenicity of
MTLE.
PMID- 27609290
TI - No association between FCGR2A and FCGR3A polymorphisms in Guillain-Barre Syndrome
in a Brazilian population.
AB - The pathogenesis of Guillain-Barre Syndrome (GBS) is not entirely understood, but
includes infection-induced aberrant immune responses. Genetic polymorphisms in Fc
gamma receptor genes (FCGR) have been associated with GBS. We assessed whether
polymorphisms rs1801274 in FCGR2A and rs396991 in FCGR3A were associated with GBS
in a Brazilian population. We genotyped 141 GBS cases and 364 healthy controls
from Brazil for both polymorphisms. The FCGR genotypes and alleles frequencies
did not differ significantly between GBS and controls. In addition, there was no
genetic association with either severity or clinical outcomes. We conclude that
these FCGR polymorphisms are not associated with susceptibility to Guillain-Barre
Syndrome in this Brazilian population.
PMID- 27609291
TI - Glioma-secreted soluble factors stimulate microglial activation: The role of
interleukin-1beta and tumor necrosis factor-alpha.
AB - We aimed to elucidate the effect of soluble factors secreted by glioma on
microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6,
significantly induced nitric oxide (NO) production and stimulated the mRNA
expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor
necrosis factor-alpha (TNF-alpha) and cyclooxygenase 2 (COX-2) in BV2 cells.
Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation,
and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2
cells. In addition, CM stimulated nuclear factor-kappaB (NF-kappaB) DNA binding
and transcriptional activity, which was repressed by SB203580. Gliomas displayed
higher mRNA expression and release of TNF-alpha and IL-1beta than primary
astrocyte cells. Neutralization of TNF-alpha and IL-1beta in C6-CM using a
neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results
indicate potential contribution of diffusible tumor-derived factors to regulate
microglial activation and subsequent tumor microenvironment.
PMID- 27609293
TI - Frequent rhabdomyolysis in anti-NMDA receptor encephalitis.
AB - The aim of this study was to analyze the clinical presentation and provocation
factors of rhabdomyolysis in anti-NMDAR encephalitis. Among the 16 patients with
anti-NMDAR encephalitis in our institutional cohort, nine patients had elevated
CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more
frequent after immunotherapy. The use of dopamine receptor blocker (DRB)
increased the risk of rhabdomyolysis. None of the patients without rhabdomyolysis
received DRBs. Rhabdomyolysis is a frequent complication in anti-NMDAR
encephalitis and more common after immunotherapy and the use of DRBs increases
the risk. Therefore, DRBs should be administered carefully in patients with anti
NMDAR encephalitis.
PMID- 27609292
TI - Ca(2+)-dependent anti-GQ1b antibody in GQ1b-seronegative Fisher syndrome and
related disorders.
AB - Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker
for Fisher syndrome and its related disorders (FS-RD), 10%-30% of the patients
are still negative in conventional assays ("GQ1b-seronegative") and the
relationship between GQ1b-seropositive and -seronegative patients has been
unclear. Some molecules require Ca(2+) cations to interact with their ligands
(Ca(2+)-dependency). Here we have investigated whether Ca(2+)-dependency is also
present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative
patients and show that IgG antibodies against GQ1b-related antigens (isolated
GQ1b and GQ1b-containing complexes) are detected Ca(2+)-dependently in the
majority of GQ1b-seronegative patients with FS-RD. The Ca(2+)-dependent
antibodies might react specifically with GQ1b-Ca(2+) conformation. This is the
first demonstration of disease-related Ca(2+)-dependent antibodies in
neurological field. GQ1b-related pathology would be involved in FS-RD more
extensively than previously revealed.
PMID- 27609294
TI - Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's
immunoregulatory effects on B cells in patients with relapsing-remitting multiple
sclerosis (RRMS).
AB - We report that B cells from patients with RRMS have decreased endogenous IFN-beta
secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in
comparison to healthy controls (HCs), which may contribute to disregulation of
cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with
loxorubin (LOX) and CpG, in combination with exogenous IFN-beta may effectively
reconstitute endogenous IFN-beta production deficit and induce the secretion of
immunoregulatory cytokines by B cells. Both LOX/IFN-beta and CpG/IFN-beta in
vitro treatments of B cells from RRMS patients induced higher endogenous IFN-beta
gene expression in comparison to the exogenous IFN-beta alone. CpG/IFN-beta
combination induced higher secretion of IL-10, TGF-beta, and IL-27 in comparison
to stimulation with IFN-beta. Our study provides a basis for future clinical
studies employing IFN-beta and TLR7/9 agonists, which may enhance the resolution
of the inflammatory response in RRMS.
PMID- 27609295
TI - Heat shock protein 70-hom gene polymorphism and protein expression in multiple
sclerosis.
AB - Immune-mediated and neurodegenerative mechanisms are involved in multiple
sclerosis (MS). Growing evidences highlight the role of HSP70 genes in the
susceptibility of some neurological diseases. In this explorative study we
analyzed a polymorphism (i.e. HSP70-hom rs2227956) of the gene HSPA1L, which
encodes for the protein hsp70-hom. We sequenced the polymorphism by polymerase
chain reaction (PCR), in 191 MS patients and 365 healthy controls. The hsp70-hom
protein expression was quantified by western blotting. We reported a strong
association between rs2227956 polymorphism and MS risk, which is independent from
the association with HSP70-2 rs1061581, and a significant link between hsp70-hom
protein expression and MS severity.
PMID- 27609297
TI - Cardiovascular benefits of lycopene: fantasy or reality?
AB - Epidemiological evidence indicates that high consumption of tomatoes and tomato
based products reduces the risk of chronic diseases such as CVD and cancer. Such
potential benefits are often ascribed to high concentrations of lycopene present
in tomato products. Mainly from the results of in vitro studies, potential
biological mechanisms by which carotenoids could protect against heart disease
and cancer have been suggested. These include cholesterol reduction, inhibition
of oxidation processes, modulation of inflammatory markers, enhanced
intercellular communication, inhibition of tumourigenesis and induction of
apoptosis, metabolism to retinoids and antiangiogenic effects. However, with
regard to CVD, results from intervention studies gave mixed results. Over fifty
human intervention trials with lycopene supplements or tomato-based products have
been conducted to date, the majority being underpowered. Many showed some
beneficial effects but mostly on non-established cardiovascular risk markers such
as lipid peroxidation, DNA oxidative damage, platelet activation and inflammatory
markers. Only a few studies showed improvement in lipid profiles, C reactive
protein and blood pressure. However, recent findings indicate that lycopene could
exert cardiovascular protection by lowering HDL-associated inflammation, as well
as by modulating HDL functionality towards an antiatherogenic phenotype.
Furthermore, in vitro studies indicate that lycopene could modulate T lymphocyte
activity, which would also inhibit atherogenic processes and confer
cardiovascular protection. These findings also suggest that HDL functionality
deserves further consideration as a potential early marker for CVD risk,
modifiable by dietary factors such as lycopene.
PMID- 27609299
TI - Gingival fibromatosis with significant de novo formation of fibrotic tissue and a
high rate of recurrence.
AB - BACKGROUND Hereditary gingival fibromatosis is characterized by slowly
progressive enlargement of the gingiva that can present as an isolated condition
or present as part of various syndromes. CASE REPORT An 11-year-old female
reported with a gingival lesion that caused masticatory problems and poor oral
hygiene. Periodontal examination revealed a dense tissue covering 30% of her
teeth crowns within both jaws. Panoramic x-ray showed a normal bone height and
teeth positioning. The patient did not use any medications, but a similar
condition was also present in other family members. The patient was diagnosed
with hereditary gingival fibromatosis. Surgery was carried out to remove excess
of gingival tissue. Post-surgical healing was uneventful, but four weeks after
the first surgery, the condition recurred amounting to 45% of the initial tissue
volume presenting in the mandible, and 25% in the maxilla. Two months later, no
significant growth was noted in the mandible, while in the maxilla, growth
increased to 40% of the preoperative state. Analysis by polarized microscope
showed a significant increase of thin fibrotic fibrils that contributed 80% of
the total pool of collagen fibrils in the patient's gingiva, but only 25% in
healthy gingiva. The patient was receiving outpatient care for follow-up every
three months and surgical intervention had not been planned as long as her
periodontal health was not be compromised. CONCLUSIONS It is currently not clear
whether the extent of the fibrosis had a mechanistic association with the ratio
of gingival tissue re-growth in our case study. Further studies are needed to
explain this association and improve the management of this condition.
PMID- 27609300
TI - A Community Health Record: Improving Health Through Multisector Collaboration,
Information Sharing, and Technology.
AB - We present a framework for developing a community health record to bring
stakeholders, information, and technology together to collectively improve the
health of a community. It is both social and technical in nature and presents an
iterative and participatory process for achieving multisector collaboration and
information sharing. It proposes a methodology and infrastructure for bringing
multisector stakeholders and their information together to inform, target,
monitor, and evaluate community health initiatives. The community health record
is defined as both the proposed framework and a tool or system for integrating
and transforming multisector data into actionable information. It is informed by
the electronic health record, personal health record, and County Health Ranking
systems but differs in its social complexity, communal ownership, and provision
of information to multisector partners at scales ranging from address to zip
code.
PMID- 27609296
TI - Specialized roles of neurofilament proteins in synapses: Relevance to
neuropsychiatric disorders.
AB - Neurofilaments are uniquely complex among classes of intermediate filaments in
being composed of four subunits (NFL, NFM, NFH and alpha-internexin in the CNS)
that differ in structure, regulation, and function. Although neurofilaments have
been traditionally viewed as axonal structural components, recent evidence has
revealed that distinctive assemblies of neurofilament subunits are integral
components of synapses, especially at postsynaptic sites. Within the synaptic
compartment, the individual subunits differentially modulate neurotransmission
and behavior through interactions with specific neurotransmitter receptors. These
newly uncovered functions suggest that alterations of neurofilament proteins not
only underlie axonopathy in various neurological disorders but also may play
vital roles in cognition and neuropsychiatric diseases. Here, we review evidence
that synaptic neurofilament proteins are a sizable population in the CNS and we
advance the concept that changes in the levels or post-translational modification
of individual NF subunits contribute to synaptic and behavioral dysfunction in
certain neuropsychiatric conditions.
PMID- 27609298
TI - Effects of alcohol, rumination, and gender on the time course of negative affect.
AB - This study modelled associations between gender, ruminative cognitive style,
alcohol use, and the time course of negative affect over the course of 43,111
random assessments in the natural environment. Participants (N = 263)
completed 49 days of experience sampling over 1.3 years. The data indicated that
rumination at baseline was positively associated with alcohol dependence symptoms
at baseline as well as higher negative affect over the course of the study.
Consistent with negative reinforcement models, drinking served to decrease the
persistence of negative affect from moment to moment. However, this ameliorative
effect of drinking was evident only among women, suggesting an increased risk for
negative reinforcement driven drinking behaviour. In addition, rumination
appeared to counteract the desired effects of alcohol on mood among women. This
suggests that women who ruminate more may be motivated to consume larger amounts
of alcohol to achieve the desired effects. Overall, the results indicate that
ruminative cognitive style and the persistence of negative affect from moment to
moment may reflect an individual vulnerability for the development of alcohol use
disorder especially among women.
PMID- 27609301
TI - Ecological Analysis of Parking Prices and Active Commuting in US Cities, 2009.
AB - We conducted an ecological study to determine whether parking prices are
associated with active commuting across US cities. We obtained parking prices for
107 US cities from the Drexel University Central Business District Public Parking
Survey, obtained city prevalence of walking and bicycling to work from the
American Community Survey, and used weighted least squares linear regression to
explore associations between parking prices and active commuting. After adjusting
for several covariates, walking to work was 3.1% higher for every additional
dollar charged for off-street daily parking, but only among more densely
populated cities, and no such association was detected for bicycling to work.
These preliminary results hint at the potential for parking policies to influence
commuting mode choice, a link that city planners and public health officials
could consider when evaluating parking policies and active transportation
behaviors.
PMID- 27609302
TI - Diabetes Screening in US Women With a History of Gestational Diabetes, National
Health and Nutrition Examination Survey, 2007-2012.
AB - INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) are at
increased risk for developing type 2 diabetes mellitus. We examined individual,
socioeconomic, and health care use characteristics of women with a history of GDM
and the association of those characteristics with diabetes screening, and we
estimated their rates of undiagnosed prediabetes and diabetes. METHODS: Using 3
cycles of the National Health and Nutrition Examination Survey (2007-2008, 2009
2010, and 2011-2012), we identified 284 women with a history of GDM who were
eligible for diabetes screening. Screening status was defined by self-report of
having had a blood test for diabetes within the prior 3 years. Undiagnosed
prediabetes and diabetes were assessed by hemoglobin A1c measurement. RESULTS:
Among women with a history of GDM, 67% reported diabetes screening within the
prior 3 years. Weighted bivariate analyses showed screened women differed from
unscreened women in measured body mass index (BMI) category (P = .01) and number
of health visits in the prior year (P = .001). In multivariable analysis,
screening was associated with a greater number of health visits in the prior year
(1 visit vs 0 visits, adjusted odds ratio [AOR], 1.91; 95% confidence interval
[CI], 0.71-5.18; 2 or 3 visits, AOR, 7.05; and >=4 visits, AOR, 5.83). Overall,
24.4% (95% CI, 18.3%-31.7%) of women had undiagnosed prediabetes and 6.5% (95%
CI, 3.7%-11.3%) had undiagnosed diabetes. CONCLUSION: More health visits in the
prior year was associated with receiving diabetes screening. Fewer opportunities
for screening may delay early detection, clinical management, and prevention of
diabetes. Prediabetes in women with a history of GDM may be underrecognized and
inadequately treated.
PMID- 27609303
TI - Differences in Receipt of Three Preventive Health Care Services by Race/Ethnicity
in Medicare Advantage Plans: Tracking the Impact of Pay for Performance, 2010 and
2013.
AB - INTRODUCTION: In 2012, the Centers for Medicare and Medicaid Services (CMS)
introduced the Quality Bonus Payment Demonstration, a pay-for-performance (P4P)
program, into Medicare Advantage plans. Previous studies documented racial/ethnic
disparities in receipt of care among participants in these plans. The objective
of this study was to determine whether P4P incentives have affected these
disparities in Medicare Advantage plans. METHODS: We studied 411 Medicare
Advantage health plans that participated in the Medicare Health Outcome Survey in
2010 and 2013. Preventive health care was defined as self-reported receipt of
health care provider communication or treatment to reduce risk of falling,
improve bladder control, and monitor physical activity among individuals
reporting these problems. Logistic regression stratified by health care plan was
used to examine racial/ethnic disparities in receipt of preventive health care
before and after the introduction of the P4P program in 2012. RESULTS: We found
similar racial/ethnic differences in receipt of preventive health care before and
after the introduction of P4P. Blacks and Asians were less likely than whites to
receive advice to improve bladder control and more likely to receive advice to
reduce risk of falling and improve physical activity. Hispanics were more likely
to report receiving advice about all 3 health issues than whites. After the
introduction of P4P, the gap decreased between Hispanics and whites for improving
bladder control and monitoring physical activity and increased between blacks and
whites for monitoring physical activity. CONCLUSION: Racial/ethnic differences in
receipt of preventive health care are not always in the expected direction. CMS
should consider developing a separate measure of equity in preventive health care
services to encourage health plans to reduce gaps among racial/ethnic groups in
receiving preventive care services.
PMID- 27609305
TI - The non-equilibrium phase diagrams of flow-induced crystallization and melting of
polyethylene.
AB - Combining extensional rheology with in-situ synchrotron ultrafast x-ray
scattering, we studied flow-induced phase behaviors of polyethylene (PE) in a
wide temperature range up to 240 degrees C. Non-equilibrium phase diagrams of
crystallization and melting under flow conditions are constructed in stress
temperature space, composing of melt, non-crystalline delta, hexagonal and
orthorhombic phases. The non-crystalline delta phase is demonstrated to be either
a metastable transient pre-order for crystallization or a thermodynamically
stable phase. Based on the non-equilibrium phase diagrams, nearly all
observations in flow-induced crystallization (FIC) of PE can be well understood.
The interplay of thermodynamic stabilities and kinetic competitions of the four
phases creates rich kinetic pathways for FIC and diverse final structures. The
non-equilibrium flow phase diagrams provide a detailed roadmap for precisely
processing of PE with designed structures and properties.
PMID- 27609304
TI - Analyses of point mutation repair and allelic heterogeneity generated by
CRISPR/Cas9 and single-stranded DNA oligonucleotides.
AB - The repair of a point mutation can be facilitated by combined activity of a
single-stranded oligonucleotide and a CRISPR/Cas9 system. While the mechanism of
action of combinatorial gene editing remains to be elucidated, the regulatory
circuitry of nucleotide exchange executed by oligonucleotides alone has been
largely defined. The presence of the appropriate CRISPR/Cas9 system leads to an
enhancement in the frequency of gene editing directed by single-stranded DNA
oligonucleotides. While CRISPR/Cas9 executes double-stranded DNA cleavage
efficiently, closure of the broken chromosomes is dynamic, as varying degrees of
heterogeneity of the cleavage products appear to accompany the emergence of the
corrected base pair. We provide a detailed analysis of allelic variance at and
surrounding the target site. In one particular case, we report sequence
alteration directed by a distinct member of the same gene family. Our data
suggests that single-stranded DNA molecules may influence DNA junction
heterogeneity created by CRISPR/Cas9.
PMID- 27609307
TI - Dynamic changes in ear temperature in relation to separation distress in dogs.
AB - Infrared thermography can visualize changes in body surface temperature that
result from stress-induced physiological changes and alterations of blood flow
patterns. Here we explored its use for remote stress monitoring (i.e. removing
need for human presence) in a sample of six pet dogs. Dogs were tested in a brief
separation test involving contact with their owner, a stranger, and social
isolation for two one-minute-periods. Tests were filmed using a thermographic
camera set up in a corner of the room, around 7m from where the subjects spent
most of the time. Temperature was measured from selected regions of both ear
pinnae simultaneously. Temperatures of both ear pinnae showed a pattern of
decrease during separation and increase when a person (either the owner or a
stranger) was present, with no lateralized temperature differences between the
two ears. Long distance thermographic measurement is a promising technique for
non-invasive remote stress assessment, although there are some limitations
related to dogs' hair structure over the ears, making it unsuitable for some
subjects.
PMID- 27609306
TI - Individual responses in biomarkers of health after marathon and half-marathon
running: is age a factor in troponin changes?
AB - Although strenuous physical activity is known to cause notable perturbations in
blood chemistries, only few studies exist observing exercise-induced simultaneous
changes in biomarkers of health status. We compared markers of muscle,
cardiovascular, renal, hepatic and inflammatory status at baseline and at 3-h and
at 48-h postrace in recreational runners who successfully completed either a
marathon (mean age 27 +/- 13 years, finishing time 199 +/- 8 min, n = 4) or half
marathon (mean age 38 +/- 13 years, finishing time 131 +/- 6 min, n = 6) race.
Significant postrace changes occurred in myoglobin (p < .001), creatinine kinase
(p < .01), CK-MB-mass (p < .01), high sensitivity troponin I (p < .05), high
sensitivity troponin T (p < .05), brain natriuretic peptide (p < .001),
creatinine (p < .01), aminotransferase enzymes (p < .001 for AST and p < .01 for
ALT), uric acid (p < .001) cortisol (p < .01), C-reactive protein (p < .05),
leukocytes (p < .001), haematocrit (p < .05) and mean corpuscular volume (p <
.01). In comparison between the two types of exercise, marathon running lead to
more pronounced responses in myoglobin, CK-MB-mass, ALT, AST, lactate and
phosphate. Notable elevations in troponin levels were observed only in young
participants (<30 years), most strikingly in those <=20 years of age. The data
indicates that prolonged running leads to distinct biomarker alterations, which
should be considered in the assessment of health status after recent acute bouts
of strenuous exercise. The observations suggesting more pronounced cardiac
troponin responses in young individuals warrant further studies in larger
populations.
PMID- 27609308
TI - Investigation of titania nanoparticles on behaviour and mechanosensory organ of
Drosophila melanogaster.
AB - Titania nanoparticles are used in food, cosmetic, medicine, paint and many more
domestic items. Its extensive use has raised the threat to the physiological
system and thus the functioning of the body. In the current study, the toxicity
of TiO2 is checked by adding it in food and using Drosophila melanogaster as a
model organism. Various concentrations of TiO2 (50, 100, 200, 250mg.L-1) toxicity
was assessed via oral route exposure. Survivability, life-cycle, mechanosensory
behaviour and structure of various mechanosensory organs were monitored as a read
out of nanoparticle toxicity. TiO2 NPs generate reactive oxygen species which can
modify multiple signalling pathways and thus can alter the development and
behavioural pattern of the fly.
PMID- 27609309
TI - iTRAQ-based proteomic analysis of LI-F type peptides produced by Paenibacillus
polymyxa JSa-9 mode of action against Bacillus cereus.
AB - : LI-F type peptides (AMP-jsa9) produced by Paenibacillus polymyxa JSa-9 are a
group of cyclic lipodepsipeptide antibiotics that exhibit a broad antimicrobial
spectrum against Gram-positive bacteria and filamentous fungi, especially
Bacillus cereus and Fusarium moniliforme. In this study, to better understand the
antibacterial mechanism of AMP-jsa9 against B. cereus, the ultrastructure of AMP
jsa9-treated B. cereus cells was observed by both atomic force microscopy and
transmission electron microscopy, and quantitative proteomic analysis was
performed on proteins extracted from treated and untreated bacterial cells by
using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC
MS/MS analysis to access differentially expressed proteins. Furthermore, multiple
experiments were conducted to validate the results of the proteomic analysis,
including determinations of ATP, NAD(+)H, NADP(+)H, reactive oxygen species
(ROS), the activities of catalase (CAT) and superoxide dismutase (SOD), and the
relative expression of target genes by quantitative real-time PCR. Bacterial
cells exposed to AMP-jsa9 showed irregular surfaces with bleb projections and
concaves; we hypothesize that AMP-jsa9 penetrated the cell wall and was anchored
on the cytoplasmic membrane and that ROS accumulated in the cell membrane after
treatment with AMP-jsa9, modulating the bacterial membrane properties and
increasing membrane permeability. Consequently, the blebs were formed on the cell
wall by the impulsive force of the leakage of intercellular contents. iTRAQ-based
proteomic analysis detected a total of 1317 proteins, including 176
differentially expressed proteins (75 upregulated (fold >2) and 101 downregulated
(fold <0.5)). Based on proteome analysis, the putative pathways of AMP-jsa9
action against B. cereus can be summarized as: (i) inhibition of bacterial
sporulation, thiamine biosynthesis, energy metabolism, DNA transcription and
translation, and cell wall biosynthesis, through direct regulation of protein
levels; and (ii) indirect effects on the same pathways through the accumulation
of ROS and the consequent impairment of cellular functions, resulting from
downregulation of antioxidant proteins, especially CAT and SOD. BIOLOGICAL
SIGNIFICANCE: The mode of action of LI-F type antimicrobial peptides (AMP-jsa9)
against B. cereus was elucidated at the proteomic level. Two pathways of AMP-jsa9
action upon B. cereus cells were identified and the mechanism of bleb formation
on the surfaces of bacterial cells was predicted based on the results of
ultrastructural observation and proteomic analysis. These results are helpful in
understanding the mechanism of LI-F type peptides and in providing the
theoretical base for applying AMP-jsa9 or its analogs to combat Gram-positive
pathogenic bacteria in the food and feed industries.
PMID- 27609310
TI - A comparison of an audiometric screening survey with an in-depth research
questionnaire for hearing loss and hearing loss risk factors.
AB - OBJECTIVE: We assessed the reliability of a hearing risk factor screening survey
used by hearing conservation programmes for noise-exposed workers. DESIGN: We
compared workers' answers from the screening survey to their answers to a
confidential research questionnaire regarding hearing loss risk factors. We
calculated kappa statistics to test the correlation between yes/no questions in
the research questionnaire compared to answers from 1 and 5 years of screening
surveys. STUDY SAMPLE: We compared the screening survey and research
questionnaire answers of 274 aluminum plant workers. RESULTS: Most of the
questions in the in-company screening survey showed fair to moderate agreement
with the research questionnaire (kappa range: -0.02, 0.57). Workers' answers to
the screening survey had better correlation with the research questionnaire when
we compared 5 years of screening answers. For nearly all questions, workers were
more likely to respond affirmatively on the research questionnaire than the
screening survey. CONCLUSIONS: Hearing conservation programmes should be aware
that workers may underreport hearing loss risk factors and functional hearing
status on an audiometric screening survey. Validating company screening tools
could help provide more accurate information on hearing loss and risk factors.
PMID- 27609311
TI - Novel genotype of Tritrichomonas foetus from cattle in Southern Africa.
AB - Bovine trichomonosis caused by Tritrichomonas foetus is a significant
reproductive disease of cattle. Preputial samples were collected using sheath
washing technique in bulls in Namibia. Thirty-six trichomonad cultures were
characterized using the TaqMan-probe commercial real-time polymerase chain
reaction (PCR) diagnostic assay (VetMAXTM-Gold Trich Detection Kit) and CYBR real
time PCR assay based on TFR3/4 primers. Diagnostic real-time PCRs and DNA
sequencing of the internal transcribed region confirmed presence of T. foetus in
35 out of 36 samples. Multilocus genotyping using cysteine proteases (CP1, CP2,
CP4, CP5, CP6, CP7, CP8, CP9) and malate dehydrogenase (MDH1) gene sequences
demonstrate that the T. foetus in Namibia are genetically distinct from those
characterized elsewhere. We report the discovery of a novel genotype of T. foetus
in Namibian cattle, distinct from other T. foetus genotypes in Europe, South and
North America and Australia. We suggest recognition of a 'Southern African'
genotype of T. foetus. Identification of the new genotype of T. foetus
demonstrates the need for wider global sampling to fully understand the diversity
and origin of T. foetus causing disease in cattle or cats.
PMID- 27609312
TI - Pimavanserin for the treatment of Parkinson's disease psychosis.
AB - INTRODUCTION: Parkinson's disease (PD) is a synucleinopathy that affects millions
of people worldwide and leads to progressive disability. Psychosis is highly
prevalent in PD patients and is associated with poor prognosis. Until April 2016,
there were no licensed drugs available in the United States of America (USA) for
the treatment of PD psychosis (PDP). Pimavanserin is the first Food and Drug
Administration approved medicine for the treatment of hallucinations and
delusions associated with PDP. AREAS COVERED: A MEDLINE literature search,
publicly available information provided by ACADIA Pharmaceuticals, and expert
opinion were used for this review. A review of PDP, its current treatment and
limitations is followed by the rationale for development of pimavanserin. The
mechanism of action, preclinical data, pharmacokinetics, pharmacodynamics, and
clinical data supporting the efficacy and safety of pimavanserin in PDP are
reviewed. We also describe the potential benefits of pimavanserin in other
contexts such as schizophrenia and sleep disorders. EXPERT OPINION: Pimavanserin
is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse
agonist) and no measurable dopaminergic activity; it has been demonstrated to be
efficacious, well tolerated and safe for the treatment of PDP. The development of
pimavanserin as an antipsychotic represents a major breakthrough in the
pharmacotherapy of psychotic symptoms associated with PD.
PMID- 27609313
TI - Disulfide Bond Pattern of Transforming Growth Factor beta-Induced Protein.
AB - Transforming growth factor beta-induced protein (TGFBIp) is an extracellular
matrix protein composed of an NH2-terminal cysteine-rich domain (CRD) annotated
as an emilin (EMI) domain and four fasciclin-1 (FAS1-1-FAS1-4) domains. Mutations
in the gene cause corneal dystrophies, a group of debilitating protein misfolding
diseases that lead to severe visual impairment. Previous studies have shown that
TGFBIp in the cornea is cross-linked to type XII collagen through a reducible
bond. TGFBIp contains 11 cysteine residues and is thus able to form five
intramolecule disulfide bonds, leaving a single cysteine residue available for
the collagen cross-link. The structures of TGFBIp and its homologues are unknown.
We here present the disulfide bridge pattern of TGFBIp, which was determined by
generating specific peptides. These were separated by ion exchange followed by
reversed-phase high-performance liquid chromatography and analyzed by mass
spectrometry and Edman degradation. The NH2-terminal CRD contains six cysteine
residues, and one of these (Cys65) was identified as the candidate for the
reducible cross-link between TGFBIp and type XII collagen. In addition, the CRD
contained two intradomain disulfide bridges (Cys49-Cys85 and Cys84-Cys97) and one
interdomain disulfide bridge to FAS1-2 (Cys74-Cys339). Significantly, this
arrangement violates the predicted disulfide bridge pattern of an EMI domain. The
cysteine residues in FAS1-3 (Cys473 and Cys478) were shown to form an intradomain
disulfide bridge. Finally, an interdomain disulfide bridge between FAS1-1 and
FAS1-2 (Cys214-Cys317) was identified. The interdomain disulfide bonds indicate
that the NH2 terminus of TGFBIp (CRD, FAS1-1, and FAS1-2) adopts a compact
globular fold, leaving FAS1-3 and FAS1-4 exposed.
PMID- 27609314
TI - Development of a brief, reliable and valid diet assessment tool for impaired
glucose tolerance and diabetes: the UK Diabetes and Diet Questionnaire.
AB - OBJECTIVE: Dietary advice is fundamental in the prevention and management of type
2 diabetes (T2DM). Advice is improved by individual assessment but existing
methods are time-consuming and require expertise. We developed a twenty-five-item
questionnaire, the UK Diabetes and Diet Questionnaire (UKDDQ), for quick
assessment of an individual's diet. The present study examined the UKDDQ's
repeatability and relative validity compared with 4 d food diaries. DESIGN: The
UKDDQ was completed twice with a median 3 d gap (interquartile range=1-7 d)
between tests. A 4 d food diary was completed after the second UKDDQ. Diaries
were analysed and food groups were mapped on to the UKDDQ. Absolute agreement
between total scores was examined using intra-class correlation (ICC). Agreement
for individual items was tested with Cohen's weighted kappa (kappa w). SETTING:
South West of England. SUBJECTS: Adults (n 177, 50.3 % women) with, or at high
risk for, T2DM; mean age 55.8 (sd 8.6) years, mean BMI 34.4 (sd 7.3) kg/m2;
participants were 91 % White British. RESULTS: The UKDDQ showed excellent
repeatability (ICC=0.90 (0.82, 0.94)). For individual items, kappa w ranged from
0.43 ('savoury pastries') to 0.87 ('vegetables'). Total scores from the UKDDQ and
food diaries compared well (ICC=0.54 (0.27, 0.70)). Agreement for individual
items varied and was good for 'alcohol' (kappa w=0.71) and 'breakfast cereals'
(kappa w=0.70), with no agreement for 'vegetables' (kappa w=0.08) or 'savoury
pastries' (kappa w=0.09). CONCLUSIONS: The UKDDQ is a new British dietary
questionnaire with excellent repeatability. Comparisons with food diaries found
agreements similar to those for international dietary questionnaires currently in
use. It targets foods and habits important in diabetes prevention and management.
PMID- 27609316
TI - Single-site substitutions improve cold activity and increase thermostability of
the dehairing alkaline protease (DHAP).
AB - To engineer dehairing alkaline protease (DHAP) variants to improve cold activity
and increase thermostability so these variants are suitable for the leather
processing industry. Based on previous studies with bacterial alkaline proteases,
double-site mutations (W106K/V149I and W106K/M124L) were introduced into the DHAP
from Bacillus pumilus. Compared with the wild-type DHAP hydrolytic activity, the
double-site variant W106K/V149I showed an increase in specific hydrolytic
activity at 15 degrees C by 2.3-fold toward casein in terms of hydrolytic rate
and 2.7-fold toward the synthetic peptide AAPF-pN by means of kcat/Km value. The
thermostability of the variant (W106K/V149I) was improved with the half-life at
60 and 70 degrees C increased by 2.7- and 5.0-fold, respectively, when compared
with the thermostability of the wild-type DHAP. Conclusively, an increase in the
cold activity and thermostability of a bacterial alkaline protease was achieved
by protein engineering.
PMID- 27609315
TI - Predictors of healthy ageing: public health policy targets.
AB - BACKGROUND: The public health policy agenda oriented towards healthy ageing
becomes the highest priority for the European countries. The article discusses
the healthy ageing concept and its possible determinants with an aim to identify
behavioral patterns related to healthy ageing in selected European countries.
METHODS: The healthy ageing is assessed based on a composite indicator of self
assessed health, functional capabilities and life meaningfulness. The logistic
regression models are used to assess the impact of the healthy lifestyle index,
psycho-social index and socio-economic status on the probability of healthy
ageing (i.e. being healthy at older age). The lifestyle and psychosocial indexes
are created as a sum of behaviors that might be important for healthy ageing.
Models are analyzed for three age groups of older people: 60-67, 68-79 and 80+ as
well as for three groups of countries representing Western, Southern and Central
Eastern Europe. RESULTS: The lifestyle index covering vigorous and moderate
physical activity, consumption of vegetables and fruits, regular consumption of
meals and adequate consumption of liquids is positively related to healthy
ageing, increasing the likelihood of being healthy at older age with each of the
items specified in the index. The score of the index is found to be significantly
higher (on average by 1 point for men and 1.1 for women) for individuals ageing
healthily. The psychosocial index covering employment, outdoor social
participation, indoor activities and life satisfaction is also found to be
significantly related to health increasing the likelihood of healthy ageing with
each point of the index score. There is an educational gradient in healthy ageing
in the population below the age of 68 and in Southern and Central-Eastern
European countries. In Western European countries, income is positively related
to healthy ageing for females. CONCLUSIONS: Stimulation physical activity and
adequate nutrition are crucial domains for a well-defined public health policy
oriented towards healthy ageing. The psychosocial elements related to social
participation, engagement, networking and life satisfaction are also found to be
health beneficial.
PMID- 27609317
TI - Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon
activating mutation in the androgen receptor gene.
AB - Mutations in the X-linked androgen receptor (AR) gene underlie complete androgen
insensitivity syndrome (CAIS), the most common cause of 46,XY sex reversal.
Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who
show normal coding region of AR. Here, we describe a novel mechanism of AR
disruption leading to CAIS in two 46,XY sisters. We analyzed whole-genome
sequencing data of the patients for pathogenic variants outside the AR coding
region. Patient fibroblasts from the genital area were used for AR cDNA analysis
and protein quantification. Analysis of the cDNA revealed aberrant splicing of
the mRNA caused by a deep intronic mutation (c.2450-118A>G) in the intron 6 of
AR. The mutation creates a de novo 5' splice site and a putative exonic splicing
enhancer motif, which leads to the preferential formation of two aberrantly
spliced mRNAs (predicted to include a premature stop codon). Patient fibroblasts
contained no detectable AR protein. Our results show that patients with CAIS and
normal AR coding region need to be examined for deep intronic mutations that can
lead to pseudoexon activation.
PMID- 27609318
TI - Formative evaluation of practice changes for managing depression within a Shared
Care model in primary care.
AB - : Aim To investigate the implementation and initial impact of the Physician
Integrated Network (PIN) mental health indicators, which are specific to
screening and managing follow-up for depression, in three primary care practices
with Shared Mental Health Care in Manitoba. BACKGROUND: Manitoba Health undertook
a primary care renewal initiative in 2006 called the PIN, which included the
development of mental health indicators specific to screening and managing follow
up for depression. These indicators were implemented in three PIN group practice
sites in Manitoba, which are also part of Shared Mental Health Care. METHODS: The
design was a non-experimental longitudinal design. A formative evaluation
investigated the implementation and initial impact of the mental health
indicators using mixed methods (document review, survey, and interview).
Quantitative data was explored using descriptive and comparative statistics and a
content and theme analysis of the qualitative interviews was conducted. Survey
responses were received from 32 out of 36 physicians from the three sites.
Interviews were conducted with 15 providers. Findings This evaluation illustrated
providers' perceived attitudes, knowledge, skills, and behaviours related to
recognizing and treating depression and expanded our understanding of primary
care processes related to managing depression related to the implementation of a
new initiative. Depression is viewed as an important problem in primary care
practice that is time consuming to diagnose, manage and treat and requires
further investigation. Implementation of the PIN mental health indicators was
variable across sites and providers. There was an increase in use of the
indicators across time and a general sentiment that benefits of screening
outweigh the costs; however, the benefit of screening for depression remains
unclear. Consistent with current guidelines, a question the findings of this
evaluation suggests is whether there are more effective ways of having an impact
on depression within primary care than screening.
PMID- 27609319
TI - Development of a Cell-penetrating Peptide that Exhibits Responsive Changes in its
Secondary Structure in the Cellular Environment.
AB - Cell-penetrating peptides (CPP) are received a lot of attention as an
intracellular delivery tool for hydrophilic molecules such as drugs, proteins,
and DNAs. We designed and synthesized nona-arginine analogues 1-5 [FAM-beta-Ala
(l-Arg-l-Arg-l-Pro)3-(Gly)3-NH2 (1), FAM-beta-Ala-(l-Arg-l-Arg-l-Pro(NH2))3
(Gly)3-NH2 (2), FAM-beta-Ala-(l-Arg-l-Arg-l-Pro(Gu))3-(Gly)3-NH2 (3), FAM-beta
Ala-(l-Arg)2-(l-Pro(Gu))2-(l-Arg)4-l-Pro(Gu)-(Gly)3-NH2 (4), and FAM-beta-Ala-(l
Arg)6-(l-Pro(Gu))3-(Gly)3-NH2 (5)] containing l-proline (l-Pro) or cationic
proline derivatives (l-Pro(NH2) and l-Pro(Gu)), and investigated their cell
penetrating abilities. Interestingly, only peptide 3 having the side-chain
guanidinyl l-Pro(Gu) exhibited a secondary structural change in cellular
environment. Specifically, peptide 3 formed a random structure in hydrophilic
conditions, whereas it formed a helical structure under amphipathic conditions.
Furthermore, during cellular permeability tests, peptide 3 demonstrated greater
cell-penetrating activity than other peptides and effectively transported plasmid
DNA into HeLa cells. Thus, l-Pro(Gu)-containing peptide 3 may be a useful
candidate as a gene delivery carrier.
PMID- 27609320
TI - A geostatistical investigation of agricultural and infrastructural risk factors
associated with primary verotoxigenic E. coli (VTEC) infection in the Republic of
Ireland, 2008-2013.
AB - Ireland reports the highest incidence of verotoxigenic Escherichia coli (VTEC)
infection in Europe. This study investigated potential risk factors for confirmed
sporadic and outbreak primary VTEC infections during 2008-2013. Overall, 989 VTEC
infections including 521 serogroup O157 and 233 serogroup O26 were geo-referenced
to 931 of 18 488 census enumeration areas. The geographical distribution of human
population, livestock, unregulated groundwater sources, domestic wastewater
treatment systems (DWWTS) and a deprivation index were examined relative to
notification of VTEC events in 524 of 6242 rural areas. Multivariate modelling
identified three spatially derived variables associated with VTEC notification:
private well usage [odds ratio (OR) 6.896, P < 0.001], cattle density (OR 1.002,
P < 0.001) and DWWTS density (OR 0.978, P = 0.002). Private well usage (OR
18.727, P < 0.001) and cattle density (OR 1.001, P = 0.007) were both associated
with VTEC O157 infection, while DWWTS density (OR 0.987, P = 0.028) was
significant within the VTEC O26 model. Findings indicate that VTEC infection in
the Republic of Ireland is particularly associated with rural areas, which are
associated with a ubiquity of pathogen sources (cattle) and pathways (unregulated
groundwater supplies).
PMID- 27609322
TI - Adolescent Patient Education Regarding ADHD Stimulant Diversion And Misuse.
AB - OBJECTIVES: Recent studies report that adolescents misuse and divert ADHD
stimulants. This study evaluates the extent to which physicians educate
adolescents with ADHD about stimulant misuse and diversion (M/D). METHODS:
Child/adolescent psychiatrists (CAP), child neurologists (CN), and developmental
behavioral pediatricians (DBP) in the US completed a questionnaire. Descriptive
statistics were performed on the final sample (n=826); multivariate regressions
were performed to identify education practice differences. RESULTS: Only 46% and
44% of physicians educate patients "often" or "very often" on health risks and
legal consequences, respectively, of stimulant M/D. CAP are more likely to
educate on health and legal consequences than CN, and more likely to educate on
legal consequences than DBP. Compared to physicians who prescribe stimulants to 1
10 patients (low prescribers), medium prescribers (11-30 patients) and high
prescribers (30+ patients) are more likely to educate about M/D. 60% of
physicians counsel patients at least "often" about M/D in a pre-college
appointment; 8% have written materials regarding M/D available. CONCLUSIONS: Many
physcians currently don't educate adolescent patients with ADHD often enough
about M/D. CN and DBP, and low prescribers, are less likely to educate about M/D.
PRACTICE IMPLICATIONS: Physicians who prescribe stimulants must educate patients
more often to prevent stimulant M/D.
PMID- 27609321
TI - Family presence and participation during medical visits of heart failure
patients: An analysis of survey and audiotaped communication data.
AB - OBJECTIVE: To describe the frequency, roles, and utility of family companion
involvement in the care of patients with Heart Failure (HF) care and to examine
the association between audiotaped patient, companion, and provider communication
behaviors. METHODS: We collected survey data and audiotaped a single medical
visit for 93 HF patients (36 brought a companion into the examination room) and
their cardiology provider. Communication data was analyzed using the Roter
Interaction Analysis System. RESULTS: There were 32% more positive rapport
building statements (p<0.01) and almost three times as many social rapport
building statements (p<0.01) from patients and companions in accompanied visits
versus unaccompanied patient visits. There were less psychosocial information
giving statements in accompanied visits compared to unaccompanied patient visits
(p<0.01.) Providers made 25% more biomedical information giving statements
(p=0.04) and almost three times more social rapport-building statements (p<0.01)
in accompanied visits. Providers asked fewer biomedical and psychosocial
questions in accompanied versus unaccompanied visits. Providers made 16% fewer
partnership-building statements in accompanied versus unaccompanied visits
(p=0.01). CONCLUSIONS: Our findings are mixed regarding the benefits of
accompaniment for facilitating patient-provider communication based on survey and
audiotaped data. PRACTICE IMPLICATIONS: Strategies to enhance engagement during
visits, such as pre-visit question prompt lists, may be beneficial.
PMID- 27609323
TI - Reversible off and on switching of prion infectivity via removing and
reinstalling prion sialylation.
AB - The innate immune system provides the first line of defense against pathogens. To
recognize pathogens, this system detects a number of molecular features that
discriminate pathogens from host cells, including terminal sialylation of cell
surface glycans. Mammalian cell surfaces, but generally not microbial cell
surfaces, have sialylated glycans. Prions or PrP(Sc) are proteinaceous pathogens
that lack coding nucleic acids but do possess sialylated glycans. We proposed
that sialylation of PrP(Sc) is essential for evading innate immunity and
infecting a host. In this study, the sialylation status of PrP(Sc) was reduced by
replicating PrP(Sc) in serial Protein Misfolding Cyclic Amplification using
sialidase-treated PrP(C) substrate and then restored to original levels by
replication using non-treated substrate. Upon intracerebral administration, all
animals that received PrP(Sc) with original or restored sialylation levels were
infected, whereas none of the animals that received PrP(Sc) with reduced
sialylation were infected. Moreover, brains and spleens of animals from the
latter group were completely cleared of prions. The current work established that
the ability of prions to infect the host via intracerebral administration depends
on PrP(Sc) sialylation status. Remarkably, PrP(Sc) infectivity could be switched
off and on in a reversible manner by first removing and then restoring PrP(Sc)
sialylation.
PMID- 27609324
TI - Australian work exposures studies: occupational exposure to pesticides.
AB - BACKGROUND: Pesticides are widely used in some occupational settings. Some
pesticides have been classified as carcinogens; however, data on the number of
workers exposed to pesticides are not available in Australia. The main aim of
this study was to estimate the current prevalence of pesticide exposure in
Australian workplaces. METHODS: The analysis used data from the Australian Work
Exposures Study, a series of nationwide telephone surveys which investigated work
related prevalence and exposure to carcinogens and asthmagens, including
pesticides, among current Australian workers. Information about the respondents'
current job and various demographic factors was collected in a telephone
interview using the web-based tool OccIDEAS. Workers were considered exposed to
pesticides if they reported applying or mixing pesticides in their current job.
RESULTS: Of the 10 371 respondents, 410 (4%) respondents were assessed as being
exposed to pesticides in the workplace, with exposure being more likely among
males, individuals born in Australia, individuals with lower education level and
those residing in regional or remote areas. Glyphosate was the most common active
ingredient used by workers. CONCLUSIONS: This is the first study to describe the
prevalence of occupational pesticide exposure in Australia and one of the few
recent studies internationally.
PMID- 27609326
TI - Resurgent coal mine dust lung disease: wave of the future or a relic of the past?
PMID- 27609327
TI - Quality of information available over internet on laparoscopic cholecystectomy.
AB - BACKGROUND: The purpose of this study was to evaluate the quality of information
available on the internet to patients undergoing laparoscopic cholecystectomy.
MATERIALS AND METHODS: The sources of information were obtained the keyword
'laparoscopic cholecystectomy', from internet searches using Google, Bing,
Yahoo!, Ask and AOL search engines with default settings. The first 50 web links
were evaluated for their accessibility, usability and reliability using the LIDA
tool (validation instrument for healthcare websites by Minervation).The
readability of the websites was assessed by using the Flesch Reading Ease Score
(FRES) and the Gunning Fog Index (GFI). RESULTS: Of the 250 links, 90 were new
links. Others were repetitions, restricted access sites or inactive links. The
websites had an average accessibility score of 52/63 (83.2%; range 40-62), a
usability score of 39/54 (73.1%; range 23-49) and a reliability score of 14/27
(51.6%; range 5-24). Average FRES was 41.07 (4.3-86.4) and average GFI was 11.2
(0.6-86.4). DISCUSSION AND CONCLUSION: Today, most people use the internet as a
convenient source of information. With regard to health issues, the information
available on the internet varies greatly in accessibility, usability and
reliability. Websites appearing at the top of the search results page may not be
the most appropriate sites for the target audience. Generally, the websites
scored low on reliability with low scores on content production and conflict-of
interest declaration. Therefore, previously evaluated references on the World
Wide Web should be given to patients and caregivers to prevent them from being
exposed to commercially motivated or inaccurate information.
PMID- 27609325
TI - Sleep-related problems in the US working population: prevalence and association
with shiftwork status.
AB - OBJECTIVE: To estimate the prevalence of a comprehensive set of self-reported
sleep problems by job characteristics, including shiftwork status, among a
representative sample of US workers. METHODS: Data for 6338 workers aged >=18
years were obtained from the National Health and Nutrition Examination Survey.
Short sleep duration was defined as <7 hours per weekday/workday. Sleep quality
was categorised as good, moderate and poor based on the frequency of 6 sleep
related symptoms. A sleep-related activities of daily living (ADL) score >=2 was
defined as impaired. Insomnia was defined as having poor sleep quality and
impaired ADL. Shiftwork status was categorised as daytime, night, evening,
rotating or another schedule. Prevalence rates were calculated and multivariate
logistic regression analyses were used. RESULTS: The prevalence of short sleep
duration (37.6% overall) was highest among night shift workers (61.8%; p<0.001).
The prevalence of poor sleep quality was 19.2% among all workers, with the
highest prevalence among night shift workers (30.7%, p=0.004). The prevalence of
impaired ADL score (24.8% overall) and insomnia (8.8% overall) was also highest
for night shift workers (36.2%, p=0.001 and 18.5%, p=0.013, respectively). In
multivariate analysis, night shift workers had the highest likelihood of these
sleep problems. CONCLUSIONS: Self-reported short sleep duration, poor sleep
quality, impaired ADL score and insomnia are common among US workers especially
among night shift workers. Although these findings should be confirmed with
objective sleep measures, they support the need for intervention programmes to
improve sleep quantity and quality among night shift workers.
PMID- 27609328
TI - Safety and effectiveness of total splenic vessel ligations in paediatric patients
with splenomegaly.
AB - BACKGROUNDS: Splenomegaly may contribute to hypersplenism and can result in
thrombocytopenia. Many approaches are used to treat splenomegaly; however, the
current management of splenomegaly has intrinsic limitations or disadvantages.
Now, we initiate a new approach, that of total splenic vessel (artery and vein)
ligations (TSVLs) in paediatric patients with splenomegaly. The purpose of our
study is to evaluate the results obtained with TVSLs procedure for paediatric
patients. PATIENTS AND METHODS: Seventeen paediatric patients with splenomegaly
were screened for enrolment into this retrospective analysis. PROCEDURE: We
identified and dissociated the splenic vessel. Next, we ligated the splenic
artery and we used clips to ligate the vein distally and proximally. RESULT: The
mean [standard deviation (SD)] splenic infarction rate of a total of 17 patients
was 77.5 (5.1)% in 6 months after operation. After TSVL, the mean count of
platelet (PLT) and white blood cell (WBC) increased significantly and reached a
steady state in the third month. Both the PLT and WBC had a significance higher
than pre-TSVL in a 1-year follow-up. CONCLUSION: Based on the evidence, we make
cautious conclusions that TSVLs are a safe and effective method in the treatment
of paediatric patients with splenomegaly, achieving a satisfactory long-term
haematological response and benefit.
PMID- 27609329
TI - Single-access laparoscopic approach in the surgical treatment of endometrial
cancer: A single-institution experience and review of literature.
AB - BACKGROUND: The aim of this study was to assess the surgical and oncological
outcome for the management of endometrial cancer (EC) by laparoendoscopic single
site surgery (LESS). PATIENTS AND METHODS: We performed a retrospective chart
review of patients who underwent a LESS for EC. All the patients were treated by
the same surgical team between July 2009 and June 2013 at the Gynaecologic
Oncologic Unit, Regina Elena National Cancer Institute, Rome, Italy. RESULTS: A
total of 50 women were included, with a median age of 45 years (range, 39-84
years) and a median body mass index (BMI) of 21.8 kg/m2 (range, 19-48 kg/m2).
Median operative time was 100 min (range, 50-240 min), median blood loss was 90
mL (range, 10-300 mL) and median hospital stay was 3 days (range, 2-9 days). The
median number of pelvic lymph nodes retrieved was 14 (range, 5-20). No
intraoperative complications occurred, but there were 4 postoperative
complications. Two patients required a laparoscopic conversion. The median follow
up was 36 months (range, 16-62 months) and no recurrence occurred. CONCLUSION:
Our report showed that the LESS approach in the treatment of early EC can be a
safe and reliable technique in terms of surgical and oncological outcomes.
PMID- 27609330
TI - Prevalence and correlates of psychological distress symptoms among patients with
substance use disorders in drug rehabilitation centers in urban Nepal: a cross
sectional study.
AB - BACKGROUND: The burden of substance misuse in developing countries is large and
increasing, with negative consequences for physical and psychological health.
Substance use disorders and psychological distress commonly co-exist, however few
studies have examined this relationship in developing countries, including Nepal.
Our aim was to investigate the prevalence of psychological distress symptoms and
associated factors among patients with substance use disorders attending drug
rehabilitation centers in Nepal. METHODS: We conducted a cross-sectional study
including 180 patients attending drug rehabilitation centers in the Kathmandu
Valley region of Nepal. We used the 6-item Kessler scale (K6) to measure symptoms
of psychological distress, and data on socio-demographics, behavioral and
psychosocial factors. Multivariable analyses were used to identify factors
associated with distress. RESULTS: The prevalence of high psychological distress
symptoms among patients with substance use disorder was 51.1 %. The mean score
found on the K6 was 12.22 (SD = 5.87). Outcomes of multivariable analyses
demonstrated various factors associated with symptoms of psychological distress,
including age (beta = -0.122, 95 % CI = -0.218; -0.026), education (beta =2.694,
95 % CI = 0.274; 5.115), severity of drug abuse (Drug Abuse Screening Test-10
DAST10)(beta = 0.262, 95 % CI = 0.022;0.502), and family functioning
(Adaptability, Partnership, Growth, Affection and Resolve-APGAR) (beta = -0.525,
95 % CI = -0.787; -0.264). CONCLUSIONS: High psychological distress symptoms are
common in patients with substance use disorder in Nepal. Demographics (age,
education), behavioral (drug abuse severity), and psychosocial factors (family
functionality) were associated with psychological distress symptoms. If confirmed
by future longitudinal studies such characteristics may assist in identifying
groups at risk for co-morbid psychological distress symptoms among patients with
substance use disorders. Future treatment approaches for substance use disorders
should address co-existing mental illness in Nepal.
PMID- 27609331
TI - Attrition of undergraduate nursing students at selected South African
universities.
AB - BACKGROUND: The nursing profession forms the backbone of many healthcare systems.
It therefore needs a consistent supply of registered nurses to deliver continuous
and safe quality healthcare, and to replace the nurses leaving or retiring from
the profession. Attrition actively occurs among nursing students in South Africa
and threatens the future supply of registered nurses. AIM: The aim of the study
was to describe the attrition rate at selected South African universities and the
factors influencing undergraduate nursing students to discontinue their nursing
studies at these universities. METHOD: A quantitative descriptive design was
followed. Heads of the nursing departments at the selected universities captured
data with a specifically designed questionnaire. Thereafter their former nursing
students provided information via a structured telephonic interview on the
reasons why they discontinued the nursing programme. RESULTS: The study revealed
that attrition of undergraduate nursing students for three intake years (2007,
2008 and 2009) at the participating universities was between 39.3% and 58.7%.
Academic and financial reasons as well as poor wellness and health were the main
causes for attrition. Another factor was failure to cope with the demands of the
clinical environment. CONCLUSION: Attrition might not occur immediately when a
nursing student is challenged, as the student might exploit the various types of
support offered. Although some nursing students do benefit from the offered
support, a large number of nursing students still discontinue the undergraduate
nursing programme.
PMID- 27609332
TI - A life uncertain - My baby's vulnerability: Mothers' lived experience of
connection with their preterm infants in a Botswana neonatal intensive care unit.
AB - BACKGROUND: Preterm and low-birth weight infants are often separated from their
mothers when admitted to neonatal units for stabilisation of body temperature and
technological support. OBJECTIVES: The aim of the study was to explore and
describe the lived experiences of mothers regarding care of their hospitalised
preterm infants in a neonatal unit in a public hospital in Gaborone, Botswana.
METHOD: This study utilised a qualitative exploratory and descriptive
phenomenological study design. Mothers of hospitalised preterm infants were
purposefully selected, with whom there was extensive engagement. Two in-depth
interviews were conducted with each participant (P). RESULTS: Mothers were
shocked by the sudden birth of a preterm infant and found the neonatal
environment intimidating. This increased their fear and anxiety and delayed
development of a relationship with their infants. Support from staff, other
mothers in the neonatal unit and family members enabled the mothers to overcome
their fear and to develop an emotional connection with their infants. CONCLUSION:
On-going supportive communication with the mothers by healthcare professionals
promotes their confidence and competence in caring for their preterm infants,
which in turn promotes mother-infant attachment.
PMID- 27609335
TI - Higher Levels of Lipoprotein Associated Phospholipase A2 is associated with
Increased Prevalence of Cognitive Impairment: the APAC Study.
AB - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a unique circulating
phospholipase with inflammatory and oxidative activities and the limited data
regarding the relationship between Lp-PLA2 and cognitive impairment are
conflicted. We conducted a cross-sectional study including 1,374 Chinese adults
recruited from 2010 to 2011, aiming to evaluate the relationship between Lp-PLA2
levels and the prevalence of cognitive impairment in a Chinese community-based
population. Participants underwent standardized evaluation. Serum Lp-PLA2 mass
was measured by ELISA. Cognition status was evaluated via the Mini-Mental Status
Exam (MMSE) and cognitive impairment was identified as MMSE <24. Multivariable
logistic regression models were used to assess the associations of Lp-PLA2 mass
with cognitive impairment. Lp-PLA2 mass was significantly associated with the
prevalence of cognitive impairment after adjusting for other potential
confounding factors (compared with the first quartile, adjusted ORs of the
second, third, and fourth quartile were 2.058 (95% CI, 0.876-4.835), 2.834 (95%
CI, 1.255-6.398), and 4.882 (95% CI, 2.212-10.777), p < 0.0001). In conclusion,
elevated level of Lp-PLA2 mass was independently associated with the prevalence
of cognitive impairment in Chinese adults.
PMID- 27609336
TI - Impact of a clinical pathway on appropriate empiric vancomycin use in cancer
patients with febrile neutropenia.
AB - Objectives Febrile neutropenia management guidelines recommend the use of
vancomycin as part of an empiric antimicrobial regimen when specific criteria are
met. Often, vancomycin use among patients with febrile neutropenia is not
indicated and may be over utilized for this indication. We sought to evaluate the
impact of implementing a febrile neutropenia clinical pathway on empiric
vancomycin use for febrile neutropenia and to identify predictors of vancomycin
use when not indicated. Methods Adult febrile neutropenia patients who received
initial therapy with an anti-pseudomonal beta-lactam with or without vancomycin
were identified before (June 2008 to November 2010) and after (June 2012 to June
2013) pathway implementation. Patients were assessed for appropriateness of
therapy based on whether the patient received vancomycin consistent with
guideline recommendations. Using a comorbidity index used for risk assessment in
high risk hematology/oncology patients, we evaluated whether specific
comorbidities are associated with inappropriate vancomycin use in the setting of
febrile neutropenia. Results A total of 206 patients were included in the pre
pathway time period with 35.9% of patients receiving vancomycin therapy that was
inconsistent with the pathway. A total of 131 patients were included in the post
pathway time period with 11.4% of patients receiving vancomycin inconsistent with
the pathway ( p = 0.001). None of the comorbidities assessed, nor the comorbidity
index score were found to be predictors of vancomycin use inconsistent with
guideline recommendations. Conclusion Our study has demonstrated that
implementation of a febrile neutropenia pathway can significantly improve
adherence to national guideline recommendations with respect to empiric
vancomycin utilization for febrile neutropenia.
PMID- 27609337
TI - Nivolumab-induced vitiligo in a metastatic melanoma patient: A case report.
AB - The programmed-death-1 inhibitors selectively block programmed-death-1
interaction with its receptor, which restores active T-cell response directed at
tumor cells, inducing an anti-tumor effect. This nonspecific activation of the
immune system can also lead to a wide spectrum of side effects. Nivolumab has
been used effectively to prolong survival in patients with metastatic melanoma
and is recommended as a category 1 agent for systemic therapy in metastatic or
unresectable melanoma per the National Comprehensive Cancer Network guidelines.
We present a case of a 64-year-old woman who began nivolumab therapy for
metastatic melanoma. After six doses of nivolumab therapy, the patient
experienced generalized hypopigmentation on her face, chest, back, arms, and
lower extremities. Although vitiligo has been reported in as many as 10.7% of
patients undergoing nivolumab therapy in some clinical trials, we believe this is
the first case to describe the progression of nivolumab-induced vitiligo in a
metastatic melanoma patient. This case provides significant insight into the
onset, symptoms, development, and treatment options for patients experiencing
vitiligo as a result of nivolumab therapy.
PMID- 27609333
TI - Urine metabolome profiling of immune-mediated inflammatory diseases.
AB - BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are a group of complex
and prevalent diseases where disease diagnostic and activity monitoring is highly
challenging. The determination of the metabolite profiles of biological samples
is becoming a powerful approach to identify new biomarkers of clinical utility.
In order to identify new metabolite biomarkers of diagnosis and disease activity,
we have performed the first large-scale profiling of the urine metabolome of the
six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis,
systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. METHODS:
Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery
cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups
were recruited representing extreme disease activity (very high vs. very low).
Metabolite association analysis with disease diagnosis and disease activity was
performed using multivariate linear regression in order to control for the
effects of clinical, epidemiological, or technical variability. After multiple
test correction, the most significant metabolite biomarkers were validated in an
independent cohort of 1200 patients and 200 controls. RESULTS: In the discovery
cohort, we identified 28 significant associations between urine metabolite levels
and disease diagnosis and three significant metabolite associations with disease
activity (P FDR < 0.05). Using the validation cohort, we validated 26 of the
diagnostic associations and all three metabolite associations with disease
activity (P FDR < 0.05). Combining all diagnostic biomarkers using multivariate
classifiers we obtained a good disease prediction accuracy in all IMIDs and
particularly high in inflammatory bowel diseases. Several of the associated
metabolites were found to be commonly altered in multiple IMIDs, some of which
can be considered as hub biomarkers. The analysis of the metabolic reactions
connecting the IMID-associated metabolites showed an over-representation of
citric acid cycle, phenylalanine, and glycine-serine metabolism pathways.
CONCLUSIONS: This study shows that urine is a source of biomarkers of clinical
utility in IMIDs. We have found that IMIDs show similar metabolic changes,
particularly between clinically similar diseases and we have found, for the first
time, the presence of hub metabolites. These findings represent an important step
in the development of more efficient and less invasive diagnostic and disease
monitoring methods in IMIDs.
PMID- 27609338
TI - The challenges of shared decision making in dementia care networks.
AB - : ABSTRACTBackground:Decision making is an important part of managing one's life
with dementia. Shared decision making is the preferred way of involving people in
decisions. Our study aimed to describe the challenges of shared decision making
in dementia care networks. METHODS: A multi-perspective qualitative study using
face-to-face interviews with 113 respondents in 23 care networks in the
Netherlands consisting of 23 people with dementia, 44 of their informal
caregivers, and 46 of their professional caregivers. The interview guide
addressed the decision topics, who were involved in the decision making and their
contributions to the decision making. We used content analysis to delineate
categories and themes. RESULTS: The themes and categories that emerged are: (1)
adapting to a situation of diminishing independence, which includes the
continuous changes in the care network, resulting in shifting decision-making
roles and the need for anticipating future decisions; and (2) tensions in network
interactions which result from different perspectives and interests and which
require reaching agreement about what constitutes a problem by exchanging
information in the care network. CONCLUSION: The challenges in dementia care
networks relate to all dimensions of social health. They have implications for a
model of shared decision making in dementia care networks. Such a model requires
flexibility regarding changing capabilities to preserve the autonomy of the
person with dementia. It needs working towards a shared view about what
constitutes a problem in the situation. It asks for professionals to advocate for
the involvement of people with dementia by helping them participate in ways that
strengthen their remaining capacities.
PMID- 27609334
TI - Glycyrrhizin protects against focal cerebral ischemia via inhibition of T cell
activity and HMGB1-mediated mechanisms.
AB - BACKGROUND: Glycyrrhizin (Gly) protects against brain injury induced by stroke.
We studied whether Gly achieves its protection by inhibiting T cell activity and
high-mobility group box 1 (HMGB1) release in the ischemic brain. METHODS: Stroke
was induced by transient middle cerebral artery occlusion in rats and mice. Gly
was injected intraperitoneally before or after stroke. We measured infarction,
neuroinflammatory cells, gene expressions of interferon-gamma (IFNgamma), IL-4,
and IL-10 in CD4 T cells, HMGB1 release, and T cell proliferation in cultured
splenocytes. RESULTS: Gly treatment reduced infarctions and neuroinflammation
characterized by the infiltration of CD68-positive macrophages and
myeloperoxidase-positive neutrophils, which corresponds to a reduction in the
number of T cells and their subsets, CD4 and CD8 T cells, in the ischemic brain,
as measured by flow cytometry. Unlike in wild-type animals, Gly did not offer
protection in nude rats and severe combined immunodeficient (SCID) mice who had
no T cells, while Gly reduced infarction in both nude rats and SCID mice whose T
cells were reconstituted, suggesting that T cells should be the target of Gly. In
addition, Gly administration inhibited T cell proliferation stimulated by ConA in
in vitro assays and inhibited HMGB1 release from the ischemic brain. Furthermore,
Gly attenuated gene expression of IFNgamma, but not IL-4 and IL-10 in CD4 T
cells. Lastly, HMGB1 promoted T cell proliferation stimulated by ConA, which was
inhibited by the addition of Gly. CONCLUSIONS: Gly blocks infarction by
inhibiting IFNgamma-mediated T cell activity, which is at least partly modulated
by HMGB1 activity.
PMID- 27609339
TI - Accommodation of the human lens capsule using a finite element model based on
nonlinear regionally anisotropic biomembranes.
AB - Accommodation of the eyes, the mechanism that allows humans to focus their vision
on near objects, naturally diminishes with age via presbyopia. People who have
undergone cataract surgery, using current surgical methods and artificial lens
implants, are also left without the ability to accommodate. The process of
accommodation is generally well known; however the specific mechanical details
have not been adequately explained due to difficulties and consequences of
performing in vivo studies. Most studies have modeled the mechanics of
accommodation under assumptions of a linearly elastic, isotropic, homogenous lens
and lens capsule. Recent experimental and numerical studies showed that the lens
capsule exhibits nonlinear elasticity and regional anisotropy. In this paper we
present a numerical model of human accommodation using a membrane theory based
finite element approach, incorporating recent findings on capsular properties.
This study seeks to provide a novel perspective of the mechanics of
accommodation. Such findings may prove significant in seeking biomedical
solutions to restoring loss of visual power.
PMID- 27609340
TI - Recent advances in interactions of designed nanoparticles and cells with respect
to cellular uptake, intracellular fate, degradation and cytotoxicity.
AB - The unique features of nanomaterials have led to their rapid development in the
biomedical field. In particular, functionalized nanoparticles (NPs) are
extensively used in the delivery of drugs and genes, bio-imaging and diagnosis.
Hence, the interaction between NPs and cells is one of the most important issues
towards understanding the true nature of the NP-mediated biological effects.
Moreover, the intracellular safety concern of the NPs as a result of
intracellular NP degradation remains to be clarified in detail. This review
presents recent advances in the interactions of designed NPs and cells. The focus
includes the governing factors on cellular uptake and the intracellular fate of
NPs, and the degradation of NPs and its influence on nanotoxicity. Some basic
consideration is proposed for optimizing the NP-cell interaction and designing
NPs of better biocompatiblity for biomedical application.
PMID- 27609341
TI - A Model-Based Strategy to Control the Spread of Carbapenem-Resistant
Enterobacteriaceae: Simulate and Implement.
AB - OBJECTIVE To reduce transmission of carbapenem-resistant Enterobacteriaceae (CRE)
in an intensive care unit with interventions based on simulations by a developed
mathematical model. DESIGN Before-after trial with a 44-week baseline period and
24-week intervention period. SETTING Medical intensive care unit of a tertiary
care teaching hospital. PARTICIPANTS All patients admitted to the unit. METHODS
We developed a model of transmission of CRE in an intensive care unit and
measured all necessary parameters for the model input. Goals of compliance with
hand hygiene and with isolation precautions were established on the basis of the
simulations and an intervention was focused on reaching those metrics as goals.
Weekly auditing and giving feedback were conducted. RESULTS The goals for
compliance with hand hygiene and contact precautions were reached on the third
week of the intervention period. During the baseline period, the calculated R0
was 11; the median prevalence of patients colonized by CRE in the unit was 33%,
and 3 times it exceeded 50%. In the intervention period, the median prevalence of
colonized CRE patients went to 21%, with a median weekly Rn of 0.42 (range, 0
2.1). CONCLUSIONS The simulations helped establish and achieve specific goals to
control the high prevalence rates of CRE and reduce CRE transmission within the
unit. The model was able to predict the observed outcomes. To our knowledge, this
is the first study in infection control to measure most variables of a model in
real life and to apply the model as a decision support tool for intervention.
Infect Control Hosp Epidemiol 2016;1-8.
PMID- 27609342
TI - The Antithrombotic Potential of Tinzaparin and Enoxaparin Upon Thrombin
Generation Triggered In Vitro by Human Ovarian Cancer Cells IGROV1.
AB - BACKGROUND: A documented relationship between ovarian cancer and thrombosis does
exist. Low-molecular-weight heparins (LMWHs) are cornerstone drugs in the primary
prevention and treatment of venous thromboembolic events in patients with cancer.
However, cancer cells may alter the efficiency of these antithrombotic agents.
OBJECTIVE: We aimed to characterize the procoagulant phenotype of human
epithelial ovarian adenocarcinoma cells, IGROV1, and to compare the capacity of
tinzaparin and enoxaparin to inhibit thrombin generation triggered by these
cells. METHODS: Thrombin generation induced by different concentrations of IGROV1
cells on platelet poor plasma (PPP) was assessed by the calibrated automated
thrombogram assay. Tissue factor (TF) expression was studied using Western blot
analysis. Then, the experimental model of thrombin generation was used to compare
the inhibitory effect of clinically relevant concentrations of both tinzaparin
and enoxaparin. The inhibitory concentration 50 (IC50) of the mean rate index and
the endogenous thrombin potential and the 2-fold increase in lag time were
analyzed on the basis of the anti-Xa and anti-IIa activities of the LMWHs.
RESULTS: IGROV1 cells suspended into PPP resulted in a significant increase in
thrombin generation in the absence of any exogenous source of TF and
phospholipids. Tissue factor was expressed by IGROV1 cells. Tinzaparin was a more
potent inhibitor of thrombin generation than enoxaparin. The inhibition of
thrombin generation induced by IGROV1 cancer cells depended mainly on the anti-Xa
activity of the LMWHs. CONCLUSION: This experimental study in ovarian cancer
cells demonstrates that the antithrombotic activity of LMWHs is not completely
predicted by the anti-Xa or anti-IIa activities measured in PPP.
PMID- 27609343
TI - Repair of inferior sternal cleft using a titanium plate in an infant with
pentalogy of Cantrell.
AB - Repair of a sternal cleft should be performed as early as possible, and the ideal
material for this treatment is autologous tissue. We report the use of a titanium
plate to repair the sternal cleft in a five-month-old patient with pentalogy of
Cantrell because of the size of the defect and the limited availability of
autologous tissue.
PMID- 27609344
TI - Role of oral zinc supplementation for reduction of neonatal hyperbilirubinemia: a
systematic review of current evidence.
AB - BACKGROUND: Neonatal hyperbilirubinemia is frequently seen condition in the NICU.
Oral zinc has been tried for the prevention of hyperbilirubinemia. AIMS: To
evaluate the role of oral zinc supplementation for reduction of neonatal
hyperbilirubinemia in term and preterm infants. METHOD: The literature search was
done for various randomized control trial (RCT) by searching the Cochrane Central
Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus,
Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical
Abstracts Service (CAS) and other data base. RESULTS: This review included six
RCT that fulfilled inclusion criteria. One study evaluated the role of zinc in
very low birth weight (VLBW) infants and remaining enrolled neonates >=35 weeks
of gestation. The dose of zinc varied from 5 to 20 mg/day and duration from 5-7
days. All the studies used zinc sulfate, only one study used zinc gluconate. The
total neonates enrolled in these different RCT are 749. CONCLUSION: Role of zinc
in the prevention of neonatal hyperbilirubinemia is not supported by the current
evidence. Only one study was able to show reduction in the mean TSB level and
requirement of phototherapy with zinc, and the remaining studies did not report
any positive effect. None of the studies showed any effect on the duration of
phototherapy, incidence of phototherapy, age of starting of phototherapy and any
serious adverse effect.
PMID- 27609346
TI - Revision of the family Sphyriocephalidae Pintner, 1913 (Cestoda: Trypanorhyncha),
with the description of Heterosphyriocephalus encarnae n. sp. and redescriptions
of two species of Sphyriocephalus.
AB - The family Sphyriocephalidae Pintner, 1913, which comprises the genera
Hepatoxylon Bosc, 1811, Sphyriocephalus Pintner, 1913 and Heterosphyriocephalus
Palm, 2004, is revised from newly-collected and museum material.
Heterosphyriocephalus encarnae n. sp. is described from the pelagic thresher,
Alopias pelagicus Nakamura (Lamniformes: Alopiidae) collected from the Pacific
Ocean off Boca del Alamo, Mexico. This species can be readily distinguished from
the rest of sphyriocephalids by its small size, low number of proglottids and
long velum with a characteristically irregular and folded border, among other
features. The tentacles show a distinctive basal armature, and a heteroacanthous
typical metabasal armature with heteromorphous hooks. Redescriptions are provided
for Sphyriocephalus tergestinus Pintner, 1913 and S. viridis (Wagener, 1854)
Pintner 1913 based on novel morphological data. A phylogenetic analysis including
the available sequences of sphyriocephalid species plus new generated sequences
of S. tergestinus has been performed, from which S. tergestinus is allocated into
Heterosphyriocephalus as H. tergestinus n. comb. New dichotomous keys for the
determination of genera of Sphyriocephalidae are provided, as well as new generic
diagnoses for Sphyriocephalus and Heterosphyriocephalus and keys for the
determination of species within both genera. Although the morphology of the genus
Hepatoxylon is not addressed in the present study, the available sequence of the
type-species has been incorporated in the phylogenetic analysis and its
relationship to the other two genera of the family is discussed.
PMID- 27609345
TI - The genome of the largest bony fish, ocean sunfish (Mola mola), provides insights
into its fast growth rate.
AB - BACKGROUND: The ocean sunfish (Mola mola), which can grow up to a length of 2.7 m
and weigh 2.3 tons, is the world's largest bony fish. It has an extremely fast
growth rate and its endoskeleton is mainly composed of cartilage. Another unique
feature of the sunfish is its lack of a caudal fin, which is replaced by a broad
and stiff lobe that results in the characteristic truncated appearance of the
fish. RESULTS: To gain insights into the genomic basis of these phenotypic
traits, we sequenced the sunfish genome and performed a comparative analysis with
other teleost genomes. Several sunfish genes involved in the growth hormone and
insulin-like growth factor 1 (GH/IGF1) axis signalling pathway were found to be
under positive selection or accelerated evolution, which might explain its fast
growth rate and large body size. A number of genes associated with the
extracellular matrix, some of which are involved in the regulation of bone and
cartilage development, have also undergone positive selection or accelerated
evolution. A comparison of the sunfish genome with that of the pufferfish (fugu),
which has a caudal fin, revealed that the sunfish contains more homeobox (Hox)
genes although both genomes contain seven Hox clusters. Thus, caudal fin loss in
sunfish is not associated with the loss of a specific Hox gene. CONCLUSIONS: Our
analyses provide insights into the molecular basis of the fast growth rate and
large size of the ocean sunfish. The high-quality genome assembly generated in
this study should facilitate further studies of this 'natural mutant'.
PMID- 27609348
TI - Rapid and Decentralized Human Waste Treatment by Microwave Radiation.
AB - This study evaluates the technical feasibility of using microwave radiation for
the rapid treatment of human feces. Human feces of 1000 g were radiated with a
commercially available household microwave oven (with rotation) at different
exposure time lengths (30, 50, 60, 70, and 75 mins) and powers (600, 800, and
1000 W). Volume reduction over 90% occurred after 1000 W microwave radiation for
75 mins. Pathogen eradiation performances of six log units or more at a high
range of microwave powers were achieved. Treatments with the same energy input of
1000 Wh, but at lower powers with prolonged exposure times, significantly
enhanced moisture removal and volume reduction. Microwave radiation caused
carbonization and resulted in a more stable end product. The energy content of
the samples after microwave treatment at 1000 W and 75 mins is 3517 +/- 8.85
calories/g of dried sample, and the product can also be used as compost.
PMID- 27609347
TI - Early prediction of acute kidney injury after transapical and transaortic aortic
valve implantation with urinary G1 cell cycle arrest biomarkers.
AB - BACKGROUND: Acute kidney injury (AKI) is a common complication following
transcatheter aortic valve implantation (TAVI) leading to increased mortality and
morbidity. Urinary G1 cell cycle arrest proteins TIMP-2 and IGFBP7 have recently
been suggested as sensitive biomarkers for early detection of AKI in critically
ill patients. However, the precise role of urinary TIMP-2 and IGFBP7 in patients
undergoing TAVI is unknown. METHODS: In a prospective observational trial, 40
patients undergoing TAVI (either transaortic or transapical) were enrolled.
Serial measurements of TIMP-2 and IGFBP7 were performed in the early post
interventional course. The primary clinical endpoint was the occurrence of AKI
stage 2/3 according to the KDIGO classification. RESULTS: Now we show, that ROC
analyses of [TIMP-2]*[IGFBP7] on day one after TAVI reveals a sensitivity of 100
% and a specificity of 90 % for predicting AKI 2/3 (AUC 0.971, 95 % CI 0.914-1.0,
SE 0.0299, p = 0.001, cut-off 1.03). In contrast, preoperative and postoperative
serum creatinine levels as well as glomerular filtration rate (GFR) and
perioperative change in GFR did not show any association with the development of
AKI. Furthermore, [TIMP-2]*[IGFBP7] remained stable in patients with AKI <=1, but
its levels increased significantly as early as 24 h after TAVI in patients who
developed AKI 2/3 in the further course (4.77 +/- 3.21 vs. 0.48 +/- 0.68, p =
0.022). Mean patients age was 81.2 +/- 5.6 years, 16 patients were male (40.0 %).
35 patients underwent transapical and five patients transaortic TAVI. 15 patients
(37.5 %) developed any kind of AKI; eight patients (20 %) met the primary
endpoint and seven patients required renal replacement therapy (RRT) within 72 h
after surgery. CONCLUSION: Early elevation of urinary cell cycle arrest
biomarkers after TAVI is associated with the development of postoperative AKI.
[TIMP-2]*[IGFBP7] provides an excellent diagnostic accuracy in the prediction of
AKI that is superior to that of serum creatinine.
PMID- 27609349
TI - Sources of Information During the 2014 West Virginia Water Crisis: A Cross
Sectional Survey.
AB - OBJECTIVE: On January 9, 2014, a faulty storage tank leaked 10,000 gallons of an
industrial coal-processing liquid into the Elk River in West Virginia,
contaminating the drinking water of 9 counties collectively known as the Kanawha
Valley. In the context of this event, we explored the relationship between social
determinants and (1) the timeliness with which residents learned about the
crisis, (2) the source of information, (3) opinions on the source of information,
(4) information-seeking behaviors, and (5) knowledge acquired. METHODS: Between
February 7 and 26, 2014, we conducted a survey of 690 adult residents of West
Virginia. Descriptive statistics and multivariable statistical models were
performed. RESULTS: Information about water contamination spread quickly, with
88% of respondents from the affected counties hearing about the incident on the
same day it occurred. Most people received the information from local television
news (73%); social media users had 120% increased odds of knowing about the
recommended behaviors. People who had a favorable opinion of the source of
information demonstrated better knowledge of recommended behaviors. CONCLUSIONS:
The use of local television news during a crisis is important for timely
dissemination of information. Information exposure across segments of the
population differed on the basis of the population's background characteristics.
(Disaster Med Public Health Preparedness. 2017;11:196-206).
PMID- 27609350
TI - Combination of extracorporeal lithotripsy and flexible ureterorenoscopy optimize
renal lithiasis therapy.
AB - OBJECTIVE: Describe our initial experience in the treatment of renal lithiasis
with extracorporeal lithotripsy controlled by simultaneous flexible
ureterorenoscopy and combined with holmium laser lithotripsy. MATERIAL AND
METHODS: We performed this novel technique in a previously selected patient with
left renal lithiasis, two in the superior calix, two in the medium calix and two
in the inferior calix, the biggest of which was placed in medium calix and was
6mm long. We proceeded to an extracorporeal shock wave lithotripsy and a
simultaneous flexible ureterorenoscopy for better controlling the fragmentation
of the lithiasis with the use of a holmium laser. In the immediate post
operative, an ultrasound was performed and, one month later, a computerized
tomography (CT) was done. RESULTS: The complete fragmentation of all the
lithiasis was obtained and a double-J catheter was placed. After the assessment
of the absence of stone fragments by CT the catheter was removed. No intra
operative or post-operative complications were described. CONCLUSIONS: The
technique described is novel, safe and reproducible. The good result obtained
through this combined technique increases our interest in continuing with its
application and consider it as an option for the treatment of renal lithiasis in
our patients.
PMID- 27609351
TI - Peripherally inserted central venous catheters in parturients with poor
peripheral venous access: a case report and assessment of potential applications.
PMID- 27609352
TI - Biotechnological Management of Skin Burn Injuries: Challenges and Perspectives in
Wound Healing and Sensory Recovery.
AB - Many wound management protocols have been developed to improve wound healing
after burn with the primordial aim to restore the barrier function of the skin
and also provide a better esthetic outcome. Autologous skin grafts remain the
gold standard in the treatment of skin burn, but this treatment has its
limitation especially for patients presenting limited donor sites due to
extensive burn areas. Deep burn injuries also alter the integrity of skin
sensitive innervation and have an impact on patient's quality of life by
compromising perceptions of touch, temperature, and pain. Thus, patients can
suffer from long-term disabilities ranging from cutaneous sensibility loss to
chronic pain. The cellular mechanisms involved in skin reinnervation following
injury are not elucidated yet. Depending on the depth of the burn, nerve
sprouting can occur from the wound bed or the surrounding healthy tissue, but
somehow this process fails to provide correct reinnervation of the wound during
scarring. In addition, several clinical observations indicate that damage to the
peripheral nervous system influences wound healing, resulting in delayed wound
healing or chronic wounds, underlining the role of innervation and neuromediators
for normal cutaneous tissue repair development. Promising tissue engineering
strategies, including the use of biomaterials, skin substitutes, and stem cells,
could provide novel alternative treatments in wound healing and help in improving
patient's sensory recovery.
PMID- 27609354
TI - Local modification of intermolecular interactions at a sub-molecule level.
AB - The local modification of intermolecular interactions in nickel-phthalocyanine
molecules (NiPCs) is investigated on an Au(111) substrate using scanning
tunneling microscopy. When the molecules are physisorbed on the substrate, they
repel each other due to induced charge dipole moments. However, when the NiPC is
chemisorbed on the substrate through the dehydrogenation of one of its ligands by
a bias pulse, we find that a nearby physisorbed NiPC is attracted to the
dehydrogenated ligand and trapped. Using our experimental results in combination
with density functional theory calculations, we show that the observed attraction
can be ascribed to the local charge redistribution around the dehydrogenated
ligand of the chemisorbed NiPC. Furthermore, we demonstrate that desorption of
the attracted NiPC from the trapped site can be readily controlled by changing
the density of NiPCs around the dehydrogenated ligand.
PMID- 27609353
TI - Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic
cell activation and drives a Th1/Th17 response.
AB - Streptococcus pneumoniae is one of the causative agent of pneumonia, meningitis,
otitis media and sepsis. Vaccination is an effective strategy to combat S.
pneumoniae invasion. We previously reported that SPY1, a novel attenuated vaccine
candidate against S. pneumoniae, induces a protective immune response against
pneumococcal infection in mice. However, underlying mechanisms have yet to be
fully illustrated. To explore the mechanism of innate and adaptive immunities
induced by SPY1. In this study, bone marrow-derived dendritic cells (DCs) of mice
were infected with SPY1 and its parental wild-type strain D39, SPY1-infected DCs
were co-cultured with homologous CD4+T cells or adoptive transfer to C57BL/6
mice. Results showed that SPY1 promoted DCs maturation with increased levels of
surface molecules such as CD40, CD86, and MHC II, and upregulated the expression
of proinflammatory cytokines, including TNF-alpha, IL-6, IL-12p40, IL-12p70 and
IL-23. By contrast, D39 did not efficiently induce DCs activation and maturation.
SPY1 could also activate MAPK and NF-kappaB signaling pathways in DC, but D39
unlikely affected this pathways. SPY1 treated DCs also induced Th1 and Th17
responses in vitro and in vivo. Our results supported the potential of SPY1 as a
novel attenuated pneumococcus vaccine, because SPY1-activated DCs exhibit fully
matured phenotype, initiated an adaptive immune response, and orchestrated Th1
and Th17 responses.
PMID- 27609355
TI - Research involving adults lacking capacity to consent: the impact of research
regulation on 'evidence biased' medicine.
AB - BACKGROUND: Society is failing in its moral obligation to improve the standard of
healthcare provided to vulnerable populations, such as people who lack decision
making capacity, by a misguided paternalism that seeks to protect them by
excluding them from medical research. Uncertainties surround the basis on which
decisions about research participation is made under dual regulatory regimes,
which adds further complexity. Vulnerable individuals' exclusion from research as
a result of such regulation risks condemning such populations to poor quality
care as a result of 'evidence biased' medicine. MAIN TEXT: This paper explores
the research regulation provisions for proxy decision making for those unable to
provide informed consent for themselves, and the subsequent legal and practical
difficulties for decision-makers. There are two separate regulatory regimes
governing research involving adults who lack capacity to consent in England and
Wales. The Mental Capacity Act 2005 governs how incapacitated adults can be
involved in research, however clinical trials of medicinal products are
separately regulated by the Medicines for Human Use (Clinical Trials) Regulations
2004. There are significant differences under these dual regimes in the
provisions for those lacking capacity to participate in medical research. The
level of risk permitted differs, with a greater requirement for justification for
participation in a clinical trial than other types of research. Who acts as proxy
decision maker, how much information is provided to the person lacking capacity,
and whether they retain the power of veto also significantly differs. CONCLUSION:
The development of two separate regulatory regimes has resulted in significant
differences between the provisions for clinical trials and other forms of
research, and from usual medical practice. The resulting uncertainty has
reinforced the tendency of those approving and conducting research to exclude
adults lacking capacity to avoid difficult decisions about seeking consent for
their participation. Future developments, such as the incoming EU Regulations,
may address some of these differences, however the justification and level of
risk permitted requires review to ensure that requirements are appropriate and
proportionate to the burdens and risks for the individual, and also to the
benefits for the wider population represented.
PMID- 27609356
TI - Hydroclimatic contrasts over Asian monsoon areas and linkages to tropical Pacific
SSTs.
AB - Knowledge of spatial and temporal hydroclimatic differences is critical in
understanding climatic mechanisms. Here we show striking hydroclimatic contrasts
between northern and southern parts of the eastern margin of the Tibetan Plateau
(ETP), and those between East Asian summer monsoon (EASM) and Indian summer
monsoon (ISM) areas during the past ~2,000 years. During the Medieval Period, and
the last 100 to 200 years, the southern ETP (S-ETP) area was generally dry (on
average), while the northern ETP (N-ETP) area was wet. During the Little Ice Age
(LIA), hydroclimate over S-ETP areas was wet, while that over N-ETP area was dry
(on average). Such hydroclimatic contrasts can be broadly extended to ISM and
EASM areas. We contend that changes in sea surface temperatures (SSTs) of the
tropical Pacific Ocean could have played important roles in producing these
hydroclimatic contrasts, by forcing the north-south movement of the Intertropical
Convergence Zone (ITCZ) and intensification/slowdown of Walker circulation. The
results of sensitivity experiments also support such a proposition.
PMID- 27609357
TI - Uterine environment and pregnancy rate of heifers with elevated plasma urea
nitrogen.
AB - Diets high in protein are associated with lower reproductive performance and
changes in the uterine environment. The objective of this study was to determine
the effect of elevated systemic concentrations of urea nitrogen on the uterine
environment and pregnancy success in beef heifers. Heifers (n=150) were matched
by breed, age, and body weight then randomly assigned to one of two dietary
treatments: 1) Control (10% CP) or 2) High protein (14% CP) over three replicates
(n=40/replicate). Estrus was synchronized with an injection of PGF2alpha. Uterine
pH, plasma urea nitrogen (PUN), ammonia, and glucose concentrations were
determined on d 7 of the estrous cycle. Pregnancy status was determined by
ultrasonography 30 d following the breeding season. In vitro fertilization was
performed on heifers precluded from uterine analysis (n=15/diet) to determine the
effect of a High Protein diet on oocyte quality. Plasma urea concentrations were
greater in the High Protein diet compared to Control (P<0.001). There was no
effect of diet on plasma ammonia (P=0.12), plasma glucose (P=0.40), uterine pH
(P=0.67), interval to estrus (P=0.54), duration of estrus (P=0.38), or pregnancy
rate (P=0.83). There was no effect of diet (P>0.40) on the number of oocytes
collected, number of oocytes cleaved, amount of blastocysts, percentage of
oocytes cleaved and percentage of blastocysts present. In summary, high nitrogen
diets increased PUN concentrations in heifers; however, there were no deleterious
effects on reproduction.
PMID- 27609358
TI - Exposure of sexually inactive males to estrogenized females increased the
investigative and consummatory sexual behavior.
AB - Two trials were conducted to evaluate the effect of diverse socio-sexual cues
upon male sexual behavior and the reproductive performance of anestrous does
(AD). Trials were conducted in northern Mexico (26 degrees N) during the natural
anestrous season (Feb-Mar) with crossbred dairy bucks. In Experiment 1, sexually
inactive bucks (SIB, n=12) were randomly allotted to three groups, four
males/group: a) DEE 9novelty stimulation) - daily exchange of estrogenized
females (EF) 12&12h, b) NEE (no novelty stimulation) - no-exchange of EF, 24h, or
c) CON (saline-treated_ -daily exchange of AF 12&12h. Sexually active bucks (SAB)
from the DEE, NEE and CON groups were subsequently exposed to AD (n=72;
n=24/group) and the reproductive outcomes were recorded. In Experiment 2, SAB
(n=12; n=6/group) were randomly divided in: 1) B+EF - males+four-EF exposed to AF
(n=36), and 2) B+NEF; males+four-saline-treated AD and exposed to AD (n=36).
Prior to the onset of the experimental breeding in both experiments, the
investigative (ISB), consummatory (CSB) and resting (RSB) sexual behavior of
males were quantified (2h*d*2d). Sexual behaviors considered were: ISB - flehmen,
ano-genital sniffing, approaches, vocalizations, kicking, penis extrusion, CSB;
mount attempts and mounts, and RSB - isolation, attempted escape, aggression and
distractions. While EF were an effective stimulus (P<0.05) for evoking mounting
in SIB males, daily exchange of estrous does used to stimulate males promoted an
enhanced response (P<0.05) in terms of both ISB and CSB. After being exposed to
AD, the B+EF bucks induced an earlier estrous response (P<0.05) as compared with
the B+NEF bucks. The untreated females did not induce any sexual activity in
males and stimulation of ovarian function did not occur when saline treated (CON)
AD were exposed to AD. Also, the B+EF group induced an enhanced increase (P<0.05)
of the male ISB and CSB, inducing in turn an increase percentage onset of estrus
in does that had previously been anestrus (P<0.05).
PMID- 27609360
TI - Single nucleotide polymorphisms in the intergenic region between metformin
transporter OCT2 and OCT3 coding genes are associated with short-term response to
metformin monotherapy in type 2 diabetes mellitus patients.
AB - OBJECTIVES: High variability in clinical response to metformin is often observed
in type 2 diabetes (T2D) patients, and it highlights the need for identification
of genetic components affecting the efficiency of metformin therapy. Aim of this
observational study is to evaluate the role of tagSNPs (tagging single nucleotide
polymorphisms) from genomic regions coding for six metformin transporter genes
with respect to the short-term efficiency. DESIGN: 102 tagSNPs in 6 genes coding
for metformin transporters were genotyped in the group of 102 T2D patients
treated with metformin for 3 months. METHODS: Most significant hits were analyzed
in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25
healthy nondiabetic volunteers was conducted to investigate the effects of
identified polymorphisms. RESULTS: In the discovery group of 102 patients, minor
alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally
associated with metformin inefficiency (P = 1.9 * 10-6 to 8.1 * 10-6). Effects of
rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from
Slovakia alone, whereas rs7757336 was significantly associated with a reduced
metformin response in combined group. In pharmacokinetic study, group of
individuals harboring risk alleles of rs7757336 and rs2481030 displayed
significantly reduced AUCinfinity of metformin in plasma. CONCLUSIONS: For the
first time, we have identified an association between the lack of metformin
response and SNPs rs3119309 and rs7757336 located in the 5' flanking region of
the genes coding for Organic cation transporter 2 and rs2481030 located in the 5'
flanking region of Organic cation transporter 3 that was supported by the results
of a pharmacokinetic study on 25 healthy volunteers.
PMID- 27609359
TI - Effect of mineralocorticoid receptor antagonists on proteinuria and progression
of chronic kidney disease: a systematic review and meta-analysis.
AB - BACKGROUND: Hypertension and proteinuria are critically involved in the
progression of chronic kidney disease. Despite treatment with renin angiotensin
system inhibition, kidney function declines in many patients. Aldosterone excess
is a risk factor for progression of kidney disease. Hyperkalaemia is a concern
with the use of mineralocorticoid receptor antagonists. We aimed to determine
whether the renal protective benefits of mineralocorticoid antagonists outweigh
the risk of hyperkalaemia associated with this treatment in patients with chronic
kidney disease. METHODS: We conducted a meta-analysis investigating
renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid
receptor antagonists in chronic kidney disease. Trials were identified from
MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials
Database. Unpublished summary data were obtained from investigators. We included
randomised controlled trials, and the first period of randomised cross over
trials lasting >=4 weeks in adults. RESULTS: Nineteen trials (21 study groups, 1
646 patients) were included. In random effects meta-analysis, addition of
mineralocorticoid receptor antagonists to renin angiotensin system inhibition
resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0,
2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular
filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m(2)). Mineralocorticoid receptor
antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a
threefold higher relative risk of withdrawing from the trial due to hyperkalaemia
(3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were
not reported in sufficient numbers to analyse. CONCLUSIONS: Mineralocorticoid
receptor antagonism reduces blood pressure and urinary protein/albumin excretion
with a quantifiable risk of hyperkalaemia above predefined study upper limit.
PMID- 27609362
TI - Prof. Thomas Buchner (22 September 1934-5 August 2016)-A leading European
hematologist and AML trialist.
PMID- 27609361
TI - Aging-Related Decline of Glutathione Peroxidase 3 and Risk of Cardiovascular
Events in Patients With Atrial Fibrillation.
AB - BACKGROUND: Experimental studies demonstrated that glutathione peroxidase 3
(GPx3), an antioxidant enzyme that catabolizes hydrogen peroxide, protects
against thrombosis. Little is known about its role in cardiovascular disease.
METHODS AND RESULTS: A prospective cohort study was conducted in 909 atrial
fibrillation patients. Serum activities of GPx3, superoxide dismutase (SOD), and
catalase were measured at baseline to assess the risk of cardiovascular events
during a mean follow-up of 43.4 months (3291 person-years). Serum Nox2 and
urinary excretion of 11-deydro-thromboxane B2 were also measured. During follow
up 160 cardiovascular events occurred (4.9%/year). Significantly lower values of
GPx3 (P<0.001) and SOD (P=0.037) were detected in patients with, compared to
those without, cardiovascular events. A lower survival rate was observed in
patients with GPx3 (P<0.001) and SOD (P=0.010) activities below the median, as
compared to those above. In a fully adjusted Cox regression model, GPx3 was the
only antioxidant enzyme predictor of cardiovascular events (hazard ratio 0.647,
95% confidence interval 0.524-0.798, P<0.001). GPx3 was inversely associated with
urinary 11-dehydro-thromboxane B2 (B -0.337, P<0.001) and serum Nox2 (B: -0.423,
P<0.001). GPx3 activity progressively decreased with decades of age (P<0.001),
with a progressive reduction in people aged >=70 years. CONCLUSIONS: This study
provides evidence that a low antioxidant status, as depicted by reduced levels of
GPx3, increases the risk of cardiovascular events in patients with atrial
fibrillation. The age-related decline of GPx3 may represent a mechanism for the
enhanced cardiovascular risk in the elderly population.
PMID- 27609363
TI - Effects of aerobic exercise performed in fasted v. fed state on fat and
carbohydrate metabolism in adults: a systematic review and meta-analysis.
AB - This study aimed to verify the effect of aerobic exercise performed in the fasted
v. fed states on fat and carbohydrate metabolism in adults. Searches were
conducted in March 2015, and updated in July 2016, using PubMed(r), Scopus and
Cochrane databases (terms: 'fasting', 'exercise', 'aerobic exercise',
'substrate', 'energy metabolism', 'fat', 'glucose', 'insulin' and 'adult') and
references from selected studies. Trials that compared the metabolic effects of
aerobic exercise (duration <=120 min) performed in the fasted v. fed states in
adults were accepted. The outcomes evaluated were fat oxidation during exercise
and the plasma concentrations of insulin, glucose and NEFA before and immediately
after exercise; two independent reviewers extracted the data (A. F. V. and L.
C.). The results were presented as weighted mean differences between treatments,
with 95 % CI. Of 10 405 articles identified, twenty-seven studies - with a total
of 273 participants - were included. There was a significant increase in fat
oxidation during exercise performed in the fasted, compared with fed, state (
3.08 g; 95 % CI -5.38, -0.79; I 2 39.1 %). The weighted mean difference of NEFA
concentrations was not significantly different between states (0.00 mmol/l; 95 %
CI -0.07, 0.08; I 2 72.7 %). However, the weighted mean differences of glucose
(0.78 mmol/l; 95 % CI 0.43, 1.14; I 2 90.8 %) and insulin concentrations (104.5
pmol/l; 95 % CI 70.8, 138.2; I 2 94.5 %) were significantly higher for exercise
performed in the fed state. We conclude that aerobic exercise performed in the
fasted state induces higher fat oxidation than exercise performed in the fed
state.
PMID- 27609364
TI - First outbreak of Crimean-Congo haemorrhagic fever in western Europe kills one
man in Spain.
PMID- 27609365
TI - Identification of Malnutrition in Critically Ill Patients via the Subjective
Global Assessment Tool: More Consideration Needed?
PMID- 27609366
TI - Developing a framework for gathering and using service user experiences to
improve integrated health and social care: the SUFFICE framework.
AB - BACKGROUND: More people than ever receive care and support from health and social
care services. Initiatives to integrate the work of health and social care staff
have increased rapidly across the UK but relatively little has been done to chart
and improve their impact on service users. Our aim was to develop a framework for
gathering and using service user feedback to improve integrated health and social
care in one locality in the North of England. METHODS: We used published
literature and interviews with health and social care managers to determine the
expected service user experiences of local community-based integrated teams and
the ways in which team members were expected to work together. We used the
results to devise qualitative data collection and analysis tools for gathering
and analyzing service user feedback. We used developmental evaluation and service
improvement methodologies to devise a procedure for developing service
improvement plans. FINDINGS: We identified six expected service user experiences
of integrated care and 15 activities that health and social care teams were
expected to undertake. We used these to develop logic models and tools for
collecting and analysing service user experiences. These include a narrative
interview schedule, a plan for analyzing data, and a method for synthesizing the
results into a composite 'story'. We devised a structured service improvement
procedure which involves teams of health and social care staff listening to a
composite service user story, identifying how their actions as a team may have
contributed to the story and developing a service improvement plan. CONCLUSIONS:
This framework aims to put service user experiences at the heart of efforts to
improve integration. It has been developed in collaboration with National Health
Service (NHS) and Social Care managers. We expect it to be useful for evaluating
and improving integrated care initiatives elsewhere.
PMID- 27609368
TI - Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission
Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque
Neovascularization.
AB - OBJECTIVE: Intraplaque neovascularization contributes to the progression and
rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is
strongly expressed by endothelial cells of tumor neovasculature and plays a major
role in hypoxia-induced neovascularization in rodent models of benign diseases.
We hypothesized that GCPII expression may play a role in intraplaque
neovascularization and may represent a target for imaging of atherosclerotic
lesions. The aim of this study was to determine frequency, pattern, and clinical
correlates of vessel wall uptake of a 68Ga-GCPII ligand for positron emission
tomographic imaging. APPROACH AND RESULTS: Data from 150 patients undergoing 68Ga
GCPII ligand positron emission tomography were evaluated. Tracer uptake in
various arterial segments was analyzed and was compared with calcified plaque
burden, cardiovascular risk factors, and immunohistochemistry of carotid
specimens. Focal arterial uptake of 68Ga-GCPII ligand was identified at 5776
sites in 99.3% of patients. The prevalence of uptake sites was highest in the
thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with
calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were
significantly associated with 68Ga-GCPII ligand accumulation, but other
cardiovascular risk factors showed no association. The number of 68Ga-GCPII
ligand uptake sites was significantly associated with overweight condition
(P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic
blocking studies indicated nonspecific tracer binding. CONCLUSIONS: 68Ga-GCPII
ligand positron emission tomography does not identify vascular lesions associated
with atherosclerotic risk. Foci of tracer accumulation are likely caused by
nonspecific tracer binding and are in part noise-related. Taken together, GCPII
may not be a priority target for imaging of atherosclerotic lesions.
PMID- 27609367
TI - Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High
Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2
Diabetes: A 22-Year Prospective Study.
AB - OBJECTIVE: To examine select adipokines, including fatty acid-binding protein 4,
retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in
relation to cardiovascular disease (CVD) mortality among patients with type 2
diabetes mellitus. APPROACH AND RESULTS: Plasma levels of fatty acid-binding
protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950
men with type 2 diabetes mellitus in the Health Professionals Follow-up Study.
After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of
whom 220 died of CVD. After multivariate adjustment for covariates, higher levels
of fatty acid-binding protein 4 were significantly associated with a higher CVD
mortality: comparing extreme tertiles, the hazard ratio and 95% confidence
interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive
association was also observed for HMW adiponectin: the hazard ratio (95%
confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme
tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly
associated with a decreased CVD mortality with an hazard ratio (95% confidence
interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis
suggested that the causal relationships of HMW adiponectin and retinol-binding
protein 4 would be directionally opposite to those observed based on the
biomarkers, although none of the Mendelian randomization associations achieved
statistical significance. CONCLUSIONS: These data suggest that higher levels of
fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD
mortality among men with type 2 diabetes mellitus. Biological mechanisms
underlying these observations deserve elucidation, but the associations of HMW
adiponectin may partially reflect altered adipose tissue functionality among
patients with type 2 diabetes mellitus.
PMID- 27609372
TI - [Chinese experts consensus on the use of oral propranolol for treatment of
infantile hemangiomas].
AB - Infantile hemangioma (IH) is one of the most common benign vascular tumors in
children. A variety of treatment methods have been documented for the management
of IH over the past years, including pharmacotherapy via oral administration or
injection of corticosteroids, vincristine, alpha interferon and bleomycin; laser
therapy, radionuclide therapy, cryotherapy and excisional surgery. The
therapeutic efficacy of each treatment modality is variable, while adverse
effects or complications are common and sometimes serious. Since the
serendipitous discovery of propranolol, a nonselective beta-adrenergic receptor
blocker, being very efficacious in treating IH in 2008, oral propranolol has
earned a role as a first-line medical therapy for complicated IH. However, the
appropriate drug dosage, dosing regimen, time for initiation, optimal duration,
monitoring for side effects remains controversial. To standardize the use of
propranolol in treating IH, avoid overtreatment or under-treatment, as well as
minimize complications, a Chinese experts consensus on the use of oral
propranolol for treatment of IH has been approved and written by a
multidisciplinary experts group based on an up-to-date literature review and
repeated discussion.
PMID- 27609369
TI - HIV, Cocaine Use, and Hepatitis C Virus: A Triad of Nontraditional Risk Factors
for Subclinical Cardiovascular Disease.
AB - OBJECTIVE: We assessed cross-sectional and longitudinal associations of 3
nontraditional cardiovascular disease risk factors-HIV, cocaine use, and chronic
hepatitis C virus infection-with 3 validated markers of subclinical
cardiovascular disease: carotid artery plaque, albuminuria, and aortic pulse wave
velocity in a well-characterized cohort. APPROACH AND RESULTS: We measured
carotid plaque at baseline and after 24 months, urine albumin/creatinine ratio
every 6 months, and pulse wave velocity annually for up to 36 months in a
predominantly black cohort of 292 participants (100 HIV negative and 192 HIV
positive). Thirty-nine percent had chronic hepatitis C virus infection and 20%,
28%, and 52% were never, past, and current cocaine users, respectively. Sixteen
percent, 47%, and 64% of those with none, 1 or 2, or all 3 nontraditional risk
factors had >=2 abnormal cardiovascular disease risk markers (P=0.001). In fully
adjusted models that included all 3 nontraditional risk factors, HIV infection
was independently associated with carotid plaque progression (increase in the
number of anatomic segments with plaque), albuminuria (albumin-creatinine ratio
>30 mg/g), albuminuria progression (doubling of albumin-creatinine ratio from
baseline to a value >30 mg/g), and pulse wave velocity. Cocaine use was
associated with an ~3-fold higher odds of carotid plaque at baseline, and
hepatitis C virus infection was significantly associated with a higher risk of
carotid plaque progression. CONCLUSIONS: These results suggest that HIV
infection, cocaine use, and hepatitis C virus infection are important
nontraditional risk factors for cardiovascular disease and highlight the need to
understand the distinct and overlapping mechanisms of the associations.
PMID- 27609373
TI - [Polymerization of flowable composite core materials irradiated by super-high
intensity light with short time].
AB - PURPOSE: To evaluate the polymerization of dual-cured flowable composite core
irradiated by super-high intensity light with short time. METHODS: The light
proof silicon rubber cuboid mold with one end open was syringed and filled by
dual-cured flowable resin composite core, then the open end of mold was
irradiated directly by a light unit at 1000 mW/cm(2) *10, *20 s; or at 3200
mW/cm(2) * 3, *6 s. The specimens were stored in the light-proof box. After
irradiation for 1 h and 24 h, Knoop microhardness was measured along the vertical
surfaces of specimens from 1mm to 10 mm depth at 1 mm interval. The data was
analyzed by one-way ANOVA with SPSS 16.0 software package. RESULTS: 3200 mW/cm(2)
*3 s light irradiation did not initiate light curing of the specimens. The other
three light irradiations could make specimens obtaining higher microhardness than
that by pure chemical cure; however, the depth of specimens affected by light
irradiation was limited. Within the area affected by light, the microhardness of
specimens could be improved by increasing the light irradiation time; after
irradiation for 24 h, the microhardness of specimens had no difference between
3200 mW/cm(2) *6 s and 1000 mW/cm(2) *20 s light irradiation. CONCLUSIONS: 3200
mW/cm(2) light intensity should be used for irradiation at least for 6 s, which
could initiate light curing of flowable composite core to sufficient
polymerization.
PMID- 27609371
TI - Hippocampal sparing radiotherapy for glioblastoma patients: a planning study
using volumetric modulated arc therapy.
AB - BACKGROUND: The purpose of this study is to investigate the potential to reduce
exposure of the contralateral hippocampus in radiotherapy for glioblastoma using
volumetric modulated arc therapy (VMAT). METHODS: Datasets of 27 patients who had
received 3D conformal radiotherapy (3D-CRT) for glioblastoma with a prescribed
dose of 60Gy in fractions of 2Gy were included in this planning study. VMAT plans
were optimized with the aim to reduce the dose to the contralateral hippocampus
as much as possible without compromising other parameters. Hippocampal dose and
treatment parameters were compared to the 3D-CRT plans using the Wilcoxon signed
rank test. The influence of tumour location and PTV size on the hippocampal dose
was investigated with the Mann-Whitney-U-test and Spearman's rank correlation
coefficient. RESULTS: The median reduction of the contralateral hippocampus
generalized equivalent uniform dose (gEUD) with VMAT was 36 % compared to the
original 3D-CRT plans (p < 0.05). Other dose parameters were maintained or
improved. The median V30Gy brain could be reduced by 17.9 % (p < 0.05). For VMAT,
a parietal and a non-temporal tumour localisation as well as a larger PTV size
were predictors for a higher hippocampal dose (p < 0.05). CONCLUSIONS: Using
VMAT, a substantial reduction of the radiotherapy dose to the contralateral
hippocampus for patients with glioblastoma is feasible without compromising other
treatment parameters. For larger PTV sizes, less sparing can be achieved. Whether
this approach is able to preserve the neurocognitive status without compromising
the oncological outcome needs to be investigated in the setting of prospective
clinical trials.
PMID- 27609374
TI - [The effect of shifting of estrogen level on the expression of estrogen receptor
and morphology of condyle in rat].
AB - PURPOSE: To evaluate the possible role and mechanism of estrogen in the
morphologic alteration process of mandibular condyle. METHODS: Forty healthy non
pregnant female 6-week-old Sprague-Dawley rats were randomly divided into control
group, contraceptive group (intragastric administration with contraceptive),
contraceptive + normal saline (intragastric administration with contraceptive and
normal saline) and contraceptive +estradiol group(intragastric administration
with contraceptive and estradiol) equally. The serum levels of estradiol were
detected respectively before the experiment, on the twelfth week and sixteenth
week. The rats were sacrificed after the experiment and the expression of
ERalpha, ERbeta of condyle was detected and histologic observation of the condyle
was performed. SPSS11.0 software package was used for statistical analysis.
RESULTS: The serum estradiol concentration of the other 3 groups were
significantly lower than control group at 12 week (P<0.05); the serum estradiol
concentration of contraceptive + estradiol group was significantly higher than
contraceptive + normal saline group on sixteenth week (P<0.05). H-E and
immunohistochemistry showed that compared with control group, not only
retrogression occurred in rat condylar cartilage but also the expression of
ERalpha and ERbeta of condylar cartilage was decreased(P<0.05) in contraceptive
group; Compared with the contraceptive + normal saline group, the retrogression
was repaired and ERalphaexpression was increased(P<0.05) while ERbeta was not
increased (P>0.05) in contraceptive + estradiol group. CONCLUSIONS: The lowered
serum estrogen would lead to retrogression in condylar cartilage. Estradiol
valerate could be used to raise concentration of serum estrogen, increase the
expression of ERalpha and slow down the process of condylar cartilage
retrogression through ER pathway.
PMID- 27609370
TI - Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES
Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).
AB - OBJECTIVE: Pathologies in the heart-brain axis might, independently or in
combination, accelerate the process of brain parenchymal loss. We aimed to
investigate the association of serum N-terminal brain natriuretic peptide (NT
proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness
(CIMT), as a marker of carotid atherosclerosis burden, with structural brain
changes. APPROACH AND RESULTS: In the longitudinal population-based AGES
Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included
2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP
and CITM (assessed by ultrasound imaging). Participants underwent a high
resolution brain magnetic resonance imaging at baseline and 5 years later to
assess total brain (TBV), gray matter, and white matter volumes. Each unit higher
log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval
[CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in
gray matter volume. Likewise, each millimeter higher CIMT was associated with
10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8)
decline in gray matter volume. There was no association between NT-proBNP and
CIMT and changes in white matter volume. Compared with participants with low NT
proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95%
CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0)
greater decline in GMW. These associations were independent of sociodemographic
and cardiovascular factors. CONCLUSIONS: Older subjects with both cardiac
dysfunction and carotid atherosclerosis are at an increased risk for brain
parenchymal loss. Accumulated pathologies in the heart-brain axis might
accelerate brain atrophy.
PMID- 27609375
TI - [The effect of shifting of estrogen level on the expression of estrogen receptor
and morphology of condyle in rat].
AB - PURPOSE: To explore the effect of cinnamaldehyde(CA) on osteogenic function and
BMP-2 expression of mice osteoblast. METHODS: MC3T3-E1 sub-clone 14 cells were
cultured in the presence of CA at 0(control group), 10, 20, 40, 80, 160, 320
MUg/mL. The cell proliferation rate was measured by MTT assay 1, 3, 5 d after
exposure. Activity of alkaline phosphatase (ALP) was detected at 3, 5, 7 d to
observe the effect of 6 concentrations of CA on osteoblast function. The mRNA
expression of BMP-2 was quantified by real-time PCR(RT-qPCR) 1, 3, 5 d after
exposure to (10,20 MUg/mL) CA. The data were analyzed by SPSS 17 software
package. RESULTS: MTT assay showed that compared with the control group, when 10,
20 MUg/mL of CA acted on MC3T3, the absorbance value decreased slightly but the
difference was not statistically significant (P>0.05), while ALP activity
increased significantly. CA increased the mRNA expression of BMP-2 at the
concentration of 10, 20 MUg/mL (P<0.05),decreased the osteoblast proliferation,
ALP activity and the mRNA expression of BMP-2 at the concentration of 40, 80,
160, 320 MUg/mL (P<0.05); as the concentration of CA increased, the effects
became more significant. CONCLUSIONS: CA(10, 20 MUg/mL) exerted positive effects
on osteogenic function, increased the ALP activity and the mRNA expression of BMP
2. It is suggested that the activity of osteoblast differentiation and osteogenic
function may be related to the expression of BMP-2.
PMID- 27609376
TI - [Osteogenic expression of rat mesenchymal stem cell on collagen and 20alpha
hydroxycholesterol loaded on the apatite of titanium].
AB - PURPOSE: To investigate the effect of composite layers loaded with 20alpha
hydroxycholesterol and collagen on the surface of apatite-coated Ti substrates on
osteogenesis of rat bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs
proliferation was quantitatively assessed by cell counting kit-8 (CCK-8). The
early osteogenic expression of BMSCs on composite layers was evaluated by
alkaline phosphatase (ALP) activity. The expression of osteocalcin (OC) and
collagen TypeI (Col I) was evaluated by Western blot. The difference between the
different groups was analyzed using SPSS 17.0 software package. RESULTS: CCK-8
results revealed that simultaneous loading of Col I and HC on biomimetic apatite
significantly promoted cell proliferation, while HC had no effect on cell
proliferation. Dual loading of Col and HC onto apatite stimulated osteogenic
differentiation in BMSCs, especially during the early stage. In addition,
individual loading of HC seemed to be more efficient than collagen in promoting
ALP activity in BMSCs. Dual loading of Col and HC synergistically promoted the
expression of OC and ColI, which were the marker of late osteogenic
differentiation. HC had no positive effect on the expression of OC and Col I.
CONCLUSIONS: Dual loading of collagen and 20alpha-hydroxycholesterol on apatite
coated titanium substrates had favourable biocompatibility and synergistically
promoted osteogenic expression.
PMID- 27609377
TI - [Establishment of traumatic occlusion model in Sprague-Dawley rats].
AB - PURPOSE: In this study, different methods were used to observe and obtain the
most effective one to establish occlusal trauma model in Sprague-Dawley rats.
METHODS: SPF male SD rats weighing 150~200 g and aged 10 to 12 weeks were used in
this study. The rats' maxillary molars were bonded with stainless steel wire,
resin , casting half crown , casting half combined crowns, half crown using
selective laser melting (SLM) technology, half combined crowns using SLM
technology through Super-bond and Multi-link bonding under general anesthesia.
After bonding, the experimental device expulsion rates were observed daily. The
data was analyzed statistically using Fisher's exact test with SAS 8.2 software
package. RESULTS: There was no significant difference between the falling rates
of using super-bond and using multi-link. Under the situation in which different
bonding methods exerted no influence on the falling rates, there was significant
difference between different experimental devices (P<0.0001). CONCLUSIONS: The
restorations fabricated with SLM technology is valid and feasible to induce
occlusal point in building occlusal trama model using SD rats.
PMID- 27609378
TI - [Analysis of retention of 3 different aesthetic Co-Cr-Mo alloy clasps on
premolars].
AB - PURPOSE: To analyze the retention of 3 different Co-Cr-Mo alloy clasps on
premolars, and provide information for clinical design of aesthetic clasps.
METHODS: An EZ20 force measuring instrument was used to record the retention of
Co-Cr-Mo alloy casting aesthetic clasps when they were dislodged from undercuts
of different depths (0.25, 0.50, 0.75 mm) on premolars. The data were analyzed
with SPSS 22.0 software passage. RESULTS: The clasp retention in groups of 0.25
and 0.5 mm undercut was three-arm clasp > varied Y-shaped clasp > modified RPI
clasp. In the group of 0.75 mm undercut, the clasp retention was varied Y-shaped
clasp>three-arm clasp>modified RPI clasp after circulations. CONCLUSIONS: A
varied Y-shaped bar clasp of 0.75 mm undercut depth is suitable for premolar both
for its adequate retention and aesthetic effect.
PMID- 27609379
TI - [Analysis of retention of 3 different aesthetic Co-Cr-Mo alloy clasps on
premolars].
AB - PURPOSE: To evaluate the 3-D surface topography of ultrasonically prepared tooth.
METHODS: Ten extracted human maxillary premolars were prepared for crowns. A
split-tooth model was used to refine the margins: half of the margin was finished
with traditional rotary instruments, the other with ultrasonic instruments. The 3
D profiles of the prepared surface were observed under scanning electron
microscopy and Talysurf CCI 3000 non-contact 3D profiler, and a quantitative
comparison of 3-D surface roughness average(SA) and the surface of skewness(SSK)
was conducted with Talymap Gold software. The data were analyzed by independent
sample t test using SPSS13.0 software package. RESULTS: The surface finished with
ultrasonic instruments exhibited a smoother surface. 3-D surface roughness
analysis showed that the SA and SSK of surfaces made by ultrasonic instruments
were significantly lower, compared with surfaces produced using conventional
rotary instruments. CONCLUSIONS: The ultrasonic instruments produce surface in
better condition than the conventional rotary instruments.
PMID- 27609380
TI - [Comparison of wear resistance and flexural strength of three kinds of bulk-fill
composite resins].
AB - PURPOSE: To compare the abrasion resistance and flexure strength of three bulk
fill resin composites with an universal nano-hybrid composite resins. METHODS:
The specimens were prepared with three kinds of bulk fill composites (SDR ,
sonicfill, Tetric N-Ceram Bulk Fill) and an universal nano-hybrid composite
resins(Herculite Precis). 10 mm in diameter * 2mm in height specimens were
prepared for abrasion resistance, while 2 mm in width * 2 mm in depth*25 mm in
length specimens were prepared for flexure strength. The specimens were mounted
in a bal1-on-disc wear testing machine and abraded with the media artificial
saliva(50 N loads, 10000 cycles).Flexural test was performed with an Universal
Testing Machine at a cross-head speed of 1mm/min. One-way variance analysis was
used to determine the statistical differences of volume loss and flexural
strength among groups with SPSS 13.0 software package(P<0.05). RESULTS: The
volume loss was as follows: SDR (1.2433+/-0.11) mm30.05). CONCLUSIONS: With regard to wear resistance and flexural
strength, Tetric N-Ceram Bulk Fill is recommended as an alternative for posterior
restorations.
PMID- 27609381
TI - [Different ways to remove necrotic periodontal ligament on delayed tooth
replantation: scanning electron microscopy and histomorphometric analysis].
AB - PURPOSE: To seek the most effective technique for removal of root-adhered
periodontal ligament. METHODS: Thirty-five roots of healthy right mandibular
first premolars extracted for orthodontic purposes were selected. After
extraction, the teeth were kept dry at room temperature for at least 1 h, and
then divided into five groups as follows: Group 1(control)-the root-adhered
periodontal ligament was preserved; Group 2 (mechanical removal)-periodontal
ligament remnants were removed by scraping root surface with a scalpel blade;
Group 3 (chemical removal 1)-removal of the periodontal ligament by immersing the
root in 1% sodium hypochlorite solution for 5 minutes; Group 4 (chemical removal
2)-removal of the periodontal ligament by immersing the root in 2% sodium
hypochlorite solution for 5 minutes; Group 5 (chemical removal 3)-removal of the
periodontal ligament by immersing the root in 1% sodium hypochlorite solution for
10 minutes. The specimens were analyzed histomorphometrically and examined under
scanning electron microscopy. Both periodontal ligament remnants and preservation
or removal of the cementum layer concomitantly with these procedures were
assessed. The data were analyzed using one-way ANOVA and Tukey's test with SAS
8.02 software package. RESULTS: In regard to periodontal ligament remnants, group
1 presented the largest areas(P<0.05), group 2 showed smaller area than group 1
(P<0.05), but much larger than group 3-5 (P<0.05); The three chemical removal
groups had no significant difference. As for preserved cementum layer, group 2
lost most areas, which showed the worst result(P<0.05). The other 4 groups had no
significant difference. CONCLUSIONS: Scraping root surface with a scalpel blade
could not wipe off the root-adhered periodontal ligament, and might damage the
cementum layer. Sodium hypochlorite solution could clean up the periodontal
ligament remnants and preserve cementum layer, which might be an ideal choice.
PMID- 27609382
TI - [Condylar morphological changes before and after orthodontic treatment for angle
Class I malocclusion adult patients].
AB - PURPOSE: To evaluate the condylar morphological changes in adult Angle Class I
malocclusionpatients before and after orthodontic treatment using a cone-beam CT
(CBCT). METHODS: Images of 25 adult Angle Class I patients (5 males, 20 females)
who had no temporomandibular joint disorder symptom were involved in this study,
and Mimics 10.01 software was used to reconstruct the three-dimensional condyle
and measure the height of condyle, the area and bone density of the largest cross
sectional plane and sagittal plane, and the volume and bone density of the whole
and upper three-dimensional condyle before and after orthodontic treatment.
Paired t test was used for comparison between pre- and post-treatment condylar
metric analysis with SPSS 19.0 software package. RESULTS: After treatment, the
area and bone density of the largest cross sectional plane and sagittal plane
were reduced significantly(P<0.05). The volume and bone density of the whole
three-dimensional condyle and bone density of the upper three-dimensional condyle
were reduced significantly(P<0.05). CONCLUSIONS: Adaptive bone remodeling of the
condyle may occur due to alternation of occlusion by orthodontic treatment in
adult Angle Class I malocclusion patients.
PMID- 27609383
TI - [Condylar morphological changes before and after orthodontic treatment for angle
Class I malocclusion adult patients].
AB - PURPOSE: To evaluate the diagnostic sensitivity and specificity of panoramic
radiography in detection of maxillary teeth roots projecting into the maxillary
sinus. METHODS: Paired panoramic radiographs and cone-beam CT (CBCT) images of
maxilla from 110 subjects were analyzed. 42 males and 68 females (15~36 years
old) with the second molars erupted completely were included. The 2 radiographic
techniques were used to observe if the roots of maxillary teeth project into the
sinus, including canine, the first premolar, the second premolar, the first molar
and the second molar. With CBCT as a gold standard, the diagnostic sensitivity
and specificity of panoramic radiography were evaluated, as well as the accuracy,
prevalence, positive likehood ratio, and negtive likehood ratio. RESULTS: The
sensitivity for canine, the first premolar, the second premolar, the first molar,
and the second molar was 100%, 100%, 96%, 99%, and 96%, respectively. The
specificity for canine, the first premolar the second premolar, the first molar,
and the second molar was 94%, 92%, 84%, 67%, and 67%, respectively. CONCLUSIONS:
Panoramic radiography has a high diagnostic sensitivity in detection of the teeth
roots projecting into the maxillary sinus for maxillary teeth. However, it can't
afford sufficient proof for orthodontic anchorage design because of low
specificity, especially for the second premolar, the first molar and the second
molar.
PMID- 27609384
TI - [Clinical effect of 3 polishing methods on resin composite restoration in filling
wedge-shaped defect].
AB - PURPOSE: To evaluate the clinical effect of 3 polishing methods on resin
composite restoration in filling wedge-shaped defect. METHODS: One hundred and
fifty patients with wedge-shaped defects were randomly divided into 3 groups.
After being filled with Nano composite resin(FILTEK Z350,3M), restorations in
group 1 were polished with Sof-lex discs system, restorations in group 2 were
polished with Super-snap system and group 3 with diamond bur and rubber cup.
Restorations in each group were reexamined and assessed utilizing standards of
USPH&Ryge after 0.5, 1 and 2 a. Chi-square test was performed using SPSS17.0
software package. RESULTS: No significant difference of secondary decay, marginal
adaption, marginal staining, surface roughness, colour matching, wearing and
gingival condition among 3 groups was found after 0.5 a and 1 a. Restorations in
group 1 and group 2 showed better performance with regards to secondary decay,
marginal adaption, marginal staining, wearing and color matching than group 3
after 2 years of restoration. CONCLUSIONS: Sof-lex discs and Super-snap polishing
system after composite filling of wedge-shaped defect was effective in reducing
secondary decay, marginal staining and wearing, as well as in maintaining the
marginal adaption, which is worthy of wide clinical application.
PMID- 27609385
TI - [Expression and clinical significance of PUMA gene in salivary adenoid cystic
carcinoma].
AB - PURPOSE: To explore the expression of p53 up-regulated modulator of apoptosis
(PUMA) gene in salivary adenoid cystic carcinoma (SACC) and its clinical
significance. METHODS: The expressions of PUMA gene and protein were detected in
27 SACC tumor-adjacent tissues (group A) and 27 SACC tumor tissues (group B) with
real-time quantitative PCR and Western blot. Statistical analysis was performed
using SPSS 19.0 software package. RESULTS: The expression of PUMA gene in groups
A as calibrator was 1,and expression of PUMA gene in group B was 0.57+/-0.17. The
expression of PUMA protein in groups A and B were 0.94+/-0.12 and 0.36+/
0.12,respectively. The expressions of PUMA gene and protein were significantly
lower in group B than in group A (P<0.05). CONCLUSIONS: The expression of puma
gene in SACC tissues is down-regulated, which is negatively correlated with the
development of SACC.
PMID- 27609386
TI - [Evaluation of the effect of one-step self etching adhesives applied in pit and
fissure sealing].
AB - PURPOSE: To observe the effect of three one-step self etching adhesive systems
used in fit and fissure sealant and explore the feasibility of application in
caries prevention in school. METHODS: Seven hundred and twenty completely erupted
mandibular first molars in 360 children aged 7 to 9 years old were chosen. The
split-mouth design was used to select one side as the experimental group, divided
into A1(Easy One Adper), B1(Adper Easy One), and C1(iBond SE).The contra lateral
teeth served as A2,B2 and C2 groups (phosphoric acid). The retention and caries
status were regularly reviewed .The clinical effect of the two groups was
compared using SPSS19.0 software package for Chi - square test. RESULTS: At 3 and
6 months, pit and fissure sealant retention rate in A1 and A2, B1 and B2,C1 and
C2 group had no significant difference. At 12 months, sealant retention in A1 and
B1 group was significantly lower than A2 and B2 group (P<0.05). No significant
difference was found between C1 and C2 groups (P>0.05). At 24 months, sealant
retention rate in A1, B1 and C1 group was significantly lower than A2, B2 and C2
group (P<0.05). The caries rate in A1and A2, B1 and B2, C1 and C2 group had no
significant difference during different follow-up time (P>0.05). CONCLUSIONS: The
clinical anticariogenic effect of three kinds of one-step etching adhesives and
phosphoric acid etching sealant was similar .One-step self etching adhesive
system was recommended for pit and fissure sealant to improve the students' oral
health. The long-term retention rate of one-step self etching adhesive system was
lower than the phosphoric acid method to long term observation is needed.
PMID- 27609387
TI - [Expression and significance of discoidin domain receptor 1 in salivary gland
mucoepidermoid carcinoma].
AB - PURPOSE: To investigate the expression and significance of discoidin domain
receptor 1 (DDR1) in salivary gland mucoepidermoid carcinoma (MEC). METHODS:
Immunohistochemical and Western blot method were used to detect the expression of
DDR1 in MEC M3SP2 and MC3 cell lines. Immunohistochemical method was used to
detect the expression of DDR1 in 58 MEC and 20 normal salivary gland tissues.
SPSS 13.0 software package was used for statistical analysis. RESULTS: The
positive expression rate of DDR1 in salivary gland MEC tissues was 79.3%,
significantly higher than 10.0% in normal salivary gland tissues (P<0.01). High
expression of DDR1 was not related to clinicopathological parameters of
MEC(P>0.05). The expression of DDR1 was positive in MEC M3SP2 and MC3 cell lines.
CONCLUSIONS: DDR1 may play an important role in carcinogenesis and progress of
salivary gland MEC.
PMID- 27609388
TI - [The effects of maxillary protraction treatment with rapid maxillary expansion
for skeletal Class III malocclusion].
AB - PURPOSE: This study evaluated the effect of maxillary protraction with rapid
maxillary expansion (RME) for adolescent skeletal Class III malocclusion cases.
The anatomical cranial structures were used to superimpose and establish the
reference grid. METHODS: Twenty cases of adolescent skeletal Class III
malocclusion treated by maxillary protraction were included as the treatment
group, another 20 cases of adolescent skeletal Class III malocclusion without
treatment were used as the control group. Cephalometric analysis according to the
reference grid superimposed by the anatomical cranial structures was carried out
before and after treatment. The data were statistically analyzed using SPSS 13.0
software package. RESULTS: There was significant increase in maxillary length(Ptm
ANS)(P<0.01).SNA and the maxillary position (A-N) differences were statistically
significant (P<0.05) while there was no significant change in maxillary sagittal
position (S-Ptm). CONCLUSIONS: It is a feasible approach to assess changes of the
hard tissue after orthopedic therapy using the reference grid superimposed by
anatomical cranial structures..
PMID- 27609389
TI - [A minimally invasive extraction technique using Benex Extraction System in
flapless immediate implant placement in anterior teeth].
AB - PURPOSE: To evaluate the feasibility and clinical outcomes of an atraumatic
extraction technique using Benex Extraction System in flapless immediate implant
placement in anterior teeth. METHODS: Twenty-five patients with single hopeless
anterior maxillary teeth were enrolled in the study. The involved teeth were
extracted using Benex Extraction System and implants were immediately placed in a
flapless way. Healing abutments were connected immediately. After 4-6 months of
healing, screw-retained implant temporary crowns were used to reshape the peri
implant gingiva. Permanent restorations were delivered 3 months later. Extraction
time was recorded and the technique feasibility was evaluated using visual
analogue scale (VAS). Peri-implant marginal bone resorption was measured in X-
ray films after loading for 1 year later. Pink esthetic score (PES) was checked
to evaluate the gingival esthetics. Questionnaire was delivered and collected to
assess patients' satisfaction on surgical experience and esthetic outcomes. SPSS
13.0 software package was used for statistical analysis. RESULTS: Twenty-five
implants osseointegrated successfully. The marginal bone resorption was (0.21+/
0.23) mm and PES was 8.8+/-1.19 after loading for 1 year. The mean extraction
time was 6.87 minutes and the VAS was 3.32. All patients were satisfied with the
final esthetic outcomes and felt comfort during surgery. CONCLUSIONS: According
to the limited data in the study, Benex extraction System is a convenient,
atraumatic and predictable technique during flapless immediate implant placement
in anterior teeth.
PMID- 27609390
TI - [Medication compliance and diet compliance in 309 oral lichen planus patients].
AB - PURPOSE: To evaluate the feasibility and clinical outcomes of an atraumatic
extraction technique using Benex Extraction System in flapless immediate implant
placement in anterior teeth. METHODS: Twenty-five patients with single hopeless
anterior maxillary teeth were enrolled in the study. The involved teeth were
extracted using Benex Extraction System and implants were immediately placed in a
flapless way. Healing abutments were connected immediately. After 4-6 months of
healing, screw-retained implant temporary crowns were used to reshape the peri
implant gingiva. Permanent restorations were delivered 3 months later. Extraction
time was recorded and the technique feasibility was evaluated using visual
analogue scale (VAS). Peri-implant marginal bone resorption was measured in X-
ray films after loading for 1 year later. Pink esthetic score (PES) was checked
to evaluate the gingival esthetics. Questionnaire was delivered and collected to
assess patients' satisfaction on surgical experience and esthetic outcomes. SPSS
13.0 software package was used for statistical analysis. RESULTS: Twenty-five
implants osseointegrated successfully. The marginal bone resorption was (0.21+/
0.23) mm and PES was 8.8+/-1.19 after loading for 1 year. The mean extraction
time was 6.87 minutes and the VAS was 3.32. All patients were satisfied with the
final esthetic outcomes and felt comfort during surgery. CONCLUSIONS: According
to the limited data in the study, Benex extraction System is a convenient,
atraumatic and predictable technique during flapless immediate implant placement
in anterior teeth.
PMID- 27609391
TI - [Analysis of three dimensional stability of the hypoplastic maxilla after
orthognathic surgery in cleft lip and palate patients].
AB - PURPOSE: To establish a three dimensional spacial measurement method to analyze
the short-term stability of maxilla after orthognathic surgery in cleft lip and
palate patients. METHODS: Twenty-five patients with maxillary hypoplasia
secondary to cleft lip and palate seeking for orthognathic surgery were included
in this study between January 2008 and September 2012. The spiral CT scan for the
skull were taken 6 weeks preoperatively (T0), 4 days postoperatively (T1),3
months postoperatively (T2), and 6 months postoperatively (T3) and collected. A
three dimensional analytic method for measuring maxilla was set up in ProPlan CMF
software, and good repeatability of identification of landmarks was confirmed.
Twenty-two indicators to describe the maxillary position and three new angles to
describe the maxillary orientation were measured and analyzed. Student's t test
was used to analyze the difference between T2 and T3 using SPSS 16.0 software
package. RESULTS: In 25 patients with cleft palate there was a translational
relapse upwards along vertical axis and a pitch-up relapse of maxilla with an
average of 7.46% at the anterior part of the cleft maxilla. The relapse rate was
30.95% in LUCLP, 8.01% in RUCLP, and 34.76% in BCLP, but with no significant
difference. Along the horizontal axis, there was a maxillary translational
relapse toward noncleft side in both LUCLP and RUCLP group, while a yaw relapse
was confirmed with the anterior part of maxilla toward noncleft side and the
posterior part toward cleft side. CONCLUSIONS: There is a three-dimensional
relapse tendency for the maxilla in the cleft patient postoperatively. The
established three-dimensional analytic method well describes the special position
of cleft maxilla especially in the translational and rotational movement of
maxilla in three different axes comparing with that from lateral cephalometry,
thus providing references for accurate measurements in study of the three
dimensional maxillary stability after orthognathic surgery.
PMID- 27609392
TI - [Clinical study of titanium mesh in conjunction with concentrate growth factors
to rebuild severe bone defect of anterior maxilla].
AB - PURPOSE: To evaluate the effect of overlaying titanium mesh with concentrate
growth factors(CGF) for rebuilding severe buccal bone defect of anterior maxilla
when used in association with dental implantation. METHODS: Twenty patients with
severe buccal bone defect of maxilla were selected. A total of 25 dental implants
were placed, including 5 cases in bilateral central incisor area and 15 cases in
unilateral central incisor area. After implantation, the defects were treated
with Bio-oss and Bio-guid in conjunction with fixation of titanium mesh and then
CGF technology was used. Two-stage surgery was carried out after 6 months of
submerged healing, and permanent prosthesis was used 3 months after temporary
restoration. The repairs of the defect were observed at the second stage surgery.
The height of margin bone around implants and the thickness of bone at implants
lingual side were measured, at the time of the second stage operation, and 3, 6,
12, 18 months after permanent restoration. The differences were analyzed by SPSS
19.0 software package with multi-sample nonparametric test and Fierdman test.
RESULTS: At the time of second operation, the bone plate at lingual side was
completely reconstructed, and new bone was formed at the top of implants.
Clinical measurements showed that the averaged thickness of bone at lingual side
was (2.69+/-0.154) mm at that time. Three, 6, 12, 18 months after restoration,
the values were (2.67+/-0.152) mm, (2.66+/-0.153) mm, (2.65+/-0.153) mm, (2.65+/
0.151) mm, respectively. Implant-abutment junction was used as a base line to
assess vertical bone absorption, the marginal bone of implant neck at lingual
side was all inferior to the base line, the distance was (0.02+/-0.048) mm,
(0.69+/-0.085) mm,(0.87+/-0.019) mm, (0.87+/-0.013) mm, respectively. Statistical
analysis showed the thickness of bone of labial side decreased significantly over
time after permanent restoration (P<0.01). Likewise, the height of marginal bone
was also decreased significantly (P<0.01). However, the difference between them
at 12 months and 18 months was not statistically significant (P>0.05).
CONCLUSIONS: The results indicate that bone augmentation at maxilla can be
achieved using titanium mesh in conjunction with CGF. The height and thickness of
newly formed bone at the implant neck margin will be stabilized after 1 year.
This method is worthy of wide clinical application.
PMID- 27609393
TI - [Longitudinal photometric analysis of facial profiles of Japanese children with
skeletal class Imalocclusion].
AB - PURPOSE: To analyze the longitudinal growth changes in facial profiles of
Japanese children with skeletal Class I malocclusion. METHODS: The subjects
consisted of 525 longitudinally taken lateral facial photographs from 57 Japanese
children (25 males and 32 females) aging from 7 to 18 years. The reference line
to standardize and evaluate serial growth changes was the er-ex line passing
through point er,the upper edge of the ear rod in a Photostat,and point
ex,ektokanthion. The profile ratios,angles,and distances from the upper/lower
lips to the E-line were measured. Longitudinal growth changes in the facial
profiles were analyzed using SPSS 12.0 software package. RESULTS: The horizontal
profile ratios of the chin showed significant differences between the sexes aging
from 8 to 13 years. The horizontal profile ratios showed characteristic changes
in both males and females from 7 to 18 years. The vertical profile ratios did not
show such remarkable changes. CONCLUSIONS: The nose and chin showed
characteristic facial growth; the nasal tip showed forward and downward growth
and the chin showed gradual protrusion. The upper lip showed slight retraction in
females but an upright tendency in males. The lower lip showed slight forward
growth. The ratios of upper to total facial height and middle to total facial
height increased and decreased,respectively. The ratio of lower to total facial
height showed few changes.
PMID- 27609394
TI - [Clinical evaluation of the zirconia all ceramic crowns in 40 consecutive
patients].
AB - PURPOSE: To investigate clinical application, aesthetics, stability and bio
compatibility of zirconia all-ceramic crowns in prosthodontic patients. METHODS:
Computer aided design and manufacturing techniques were used to make zirconia all
ceramic crowns in 40 patients. They were divided into 2 groups according to the
thickness of the gingival thickness. After 12 months of clinical observation, the
aesthetics, stability, and bio-compatibility were evaluated by the crown color,
crown edge fitness, losing ratio and gingival health. The data were analyzed
using SPSS 13.0 software package. RESULTS: Slight marginal discrepancy was
observed in 2 zirconia all ceramic crowns, no evidence of decay was observed at 1
year. CONCLUSIONS: Zirconia all ceramic crowns have a low fracture rate, good
biological properties and excellent esthetic properties. It is ideal esthetic
prosthesis.
PMID- 27609395
TI - [Effects of using different dose of dexmedetomidine during tracheal extubation
for patients with parotidectomy after general anesthesia].
AB - PURPOSE: To observe the effects of using different-dose dexmedetomidine during
tracheal extubation for patients with parotidectomy after general anesthesia.
METHODS: Eighty patients with "ASA I-II"scheduled for parotidectomy under general
anesthesia were randomly divided into 4 groups, dexmedetomidine group (D1, D2, D3
group) and control group (C group), 20 cases in each group. Anesthesia induction
and maintenance were the same. Thirty minutes before the end of surgery, patients
in group D1,D2,D3 and group C were infused dexmedetomidine 0.4, 0.8, 1.2 MUg/kg
diluted to 20 mL and the same volume of normal saline respectively within 10
minutes. After surgery, all patients were sent to the PACU. Extubation was
applied to the patients who had extubation indications. SBP, DBP and HR were
recorded at each time-point including T0(before induction), T1(the time when
extubation, T2(5 min after extubation) and T3(10 min after extubation).The
conditions of patients' bucking and agitation in PACU were also recorded. Other
recorded indications included Ramsay scores and NRS at the time of extubation,
extubation time and orientation recovery time. Statistical analysis was performed
using SPSS20.0 software package. RESULTS: SBP, DBP and HR at the time of
extubation in group C, D1 increased significantly compared with those before
extubation (P<0.05). SBP, DBP and HR in group D1 had no significant difference at
T0, T1, T2 and T3 from those in group C (P>0.05). Ramsay scores and NRS in group
D1 had no significant difference from those in group C (P>0.05). The incidence
and degree of bucking in group D1 had declining tendency, but the difference was
not significant (P>0.05). SBP, DBP and HR in group D2, D3 were significantly
lower at each time-point than those in group C, D1 (P<0.05). The incidence and
degree of bucking and agitation in group D2, D3 were lower and lighter than those
in group C, D1 and Ramsay scores, NRS also had significant difference (P<0.05).
Ramsay scores in group D3 were higher than those in group D2, and NRS in group D3
were significantly lower (P<0.05). Extubation time and orientation recovery time
of group D3 were significantly longer than those in group D1, D2 and C (P<0.05).
CONCLUSIONS: Dexmedetomidine infusion before the end of parotidectomy can reduce
hemodynamic fluctuation during the recovery period and improve the recovery
quality. Moderate dose of dexmedetomidine (0.8 MUg/kg) was more secure, and would
not extend the extubation and orientation recovery time.
PMID- 27609396
TI - [A clinical study on blood pressure changes before and after tooth extraction in
649 elderly patients].
AB - PURPOSE: To investigate the safety of tooth extraction under ECG monitoring in
649 senile patients with hypertension by observing the blood pressure changes
during operation. METHODS: The patients were divided into hypertension group and
non-hypertension group. ECG monitoring was carried out during extraction. Blood
pressure changes were monitored and recorded. The data was statistically analyzed
with SPSS 18.0 software package. RESULTS: The patients' blood pressure in the two
groups increased as a result of tooth extraction, and the change was more obvious
in patients with hypertension. When blood pressure was controlled to normal
range, there was no significant difference in blood pressure between the
hypertension group and non-hypertension group. The increase of blood pressure of
patients taking beta-receptor blockers was minimal. CONCLUSIONS: Preoperative
blood pressure control is important for reducing surgical risk in patients with
hypertension during ECG monitoring extraction.
PMID- 27609397
TI - [Dental education for college students based on WeChat public platform].
AB - The authors proposed a model for dental education based on WeChat public
platform. In this model, teachers send various kinds of digital teaching
information such as PPT,word and video to the WeChat public platform and students
share the information for preview before class and differentiate the key-point
knowledge from those information for in-depth learning in class. Teachers also
send reference materials for expansive learning after class. Questionaire through
the WeChat public platform is used to evaluate teaching effect of teachers and
improvement may be taken based on the feedback questionnaire. A discussion and
interaction based on WeCchat between students and teacher can be aroused on a
specific topic to reach a proper solution. With technique development of mobile
terminal, mobile class will come true in near future.
PMID- 27609398
TI - [Pigmented villonodular synovitis of the temporomandibular joint:report of one
case and review of literatures].
AB - Pigmented villonodular synovitis (PVNS) is a benign, proliferative disorder of
synovium. It often affects the knee, and rarely occurs in the temporomandibular
joint (TMJ). This paper reported a 45-year-old male patient with PVNS of the TMJ,
who was referred with a chief complaint of slowly growing and painless
preauricular mass that was noticed about 1 year. Radical excision and follow-up
were conducted, no recurrence and metastasis were noted.
PMID- 27609399
TI - Ondansetron for pediatric concussion; a pilot study for a randomized controlled
trial.
AB - OBJECTIVES: Assess the feasibility of a study evaluating one dose of oral
ondansetron to decrease post-concussion symptoms at one week and one month
following concussion in children aged 8 to 17 years old. METHOD: This was a pilot
study for a randomized, triple-blind controlled trial of one dose of either
ondansetron or placebo performed in a tertiary care pediatric emergency
department. Participants were children aged 8 to 17 years who sustained a
concussion in the previous 24 hours and visited a single emergency department.
The outcome of interest was an increase from pre-concussion baseline of at least
3 symptoms from the Post-Concussion Symptom Inventory, measured at one week and
at one month following concussion. The primary outcome was to determine the
proportion of children who completed the assessment at one week following the
intervention. Secondary outcome was the proportion of children who completed the
assessment at one month following the intervention. All children, care givers,
and those assessing the outcomes were blinded to the group assignment. RESULTS:
Of the 218 children presenting with a concussion during the study period, we
screened 108 and found 36/108 (33%) eligible to participate and 16/108 (14.8%)
agreed to participate. All enrolled patients were compliant with the intervention
and follow-up. CONCLUSION: In our study population, approximately one-third of
the screened concussion patients were eligible to participate and approximately
one half of those eligible agreed to participate. Our study found that most
enrolled patients preferred electronic follow-up; the noncompliance rate was
minimal.
PMID- 27609400
TI - Lifestyle and IVF Outcomes.
AB - Whereas much has been written about the prognostic factors associated with
outcomes of in vitro fertilization (IVF) such as female age, diagnosis, and
ovarian reserve, relatively little attention has been devoted to patient-oriented
lifestyles that may influence IVF outcomes. Patients are particularly interested
in this topic because many patients wish to partner with their physicians and
want to know specific behaviors to improve their chances of IVF success. This
brief review is not intended as an exhaustive literature search of all possible
lifestyles that may influence assisted reproductive outcome nor is it intended to
be a comprehensive review of individual topics. It does give, however, a brief
overview of a number of areas in which patient-specific behaviors may influence
outcomes in assisted reproduction. Specifically, this review will look at the
effects of smoking, alcohol consumption, caffeine, diet, exercise, and exposure
to the reproductive toxin bisphenol A on IVF outcomes.
PMID- 27609401
TI - The Synergic In Vitro Tocolytic Effect of Nifedipine Plus Ritodrine on Human
Myometrial Contractility.
AB - Many pharmacological agents have been investigated to manage preterm labor; we
postulate that a combination of tocolytic drugs may achieve a better effect in
the prevention of uterine contractions without dose-dependent adverse effects.
The aim of this study was to evaluate the inhibitory effect of dual combinations
of tocolytics in vitro. Human myometrium was obtained during elective cesarean
sections (term without labor; n = 40). Myometrial strips were placed in organ
baths for the measurement of isometric tension. Contractile activity was induced
by oxytocin (10-8 mol/L), then a concentration-response curve to single or dual
combinations of tocolytics was started. All studied tocolytics (nifedipine,
ritodrine, nitroglycerin, atosiban, and NS-1619), when used alone, significantly
inhibited myometrial contractions. When combined, nifedipine plus ritodrine
produced a significantly greater inhibition of contractility than each drug alone
in the midrange of concentrations. The combination of nifedipine plus
nitroglycerin or nifedipine plus atosiban produced a significantly greater
inhibition than nitroglycerin or atosiban alone but not greater than nifedipine.
The combination of nifedipine plus NS-1619 (Ca+2-activated K+ [BKCa] channel
opener) reduced the inhibitory effect of each drug. We concluded that a selected
combination of tocolytics (nifedipine plus ritodrine) produced a significantly
greater inhibitory effect on contractility than each drug alone at intermediate
concentrations. Thus, specific combinations of tocolytics with different
intracellular signaling pathways may have a synergic effect constituting a
provocative new option for preterm labor treatment.
PMID- 27609402
TI - Cell therapy for basement membrane-linked diseases.
AB - For most disorders caused by mutations in genes encoding basement membrane (BM)
proteins, there are at present only limited treatment options available. Genetic
BM-linked disorders can be viewed as especially suited for treatment with cell
based therapy approaches because the proteins that need to be restored are
located in the extracellular space. In consequence, complete and permanent
engraftment of cells does not necessarily have to occur to achieve substantial
causal therapeutic effects. For these disorders cells can be used as transient
vehicles for protein replacement. In addition, it is becoming evident that BM
linked genetic disorders are modified by secondary diseases mechanisms. Cell
based therapies have also the ability to target such disease modifying
mechanisms. Thus, cell therapies can simultaneously provide causal treatment and
symptomatic relief, and accordingly hold great potential for treatment of BM
linked disorders. However, this potential has for most applications and diseases
so far not been realized. Here, we will present the state of cell therapies for
BM-linked diseases. We will discuss use of both pluripotent and differentiated
cells, the limitation of the approaches, their challenges, and the way forward to
potential wider implementation of cell therapies in the clinics.
PMID- 27609405
TI - Stabilization of species coexistence in spatial models through the aggregation
segregation effect generated by local dispersal and nonspecific local
interactions.
AB - Spatial interactions are widely acknowledged to play a significant role in
sustaining diversity in ecological communities. However, theoretical work on this
topic has focused on how spatial processes affect coexistence of species that
differ in their strategies, with less attention to how spatial processes matter
when competitors are equivalent. Furthermore, though it is recognized that models
with local dispersal and local competition may sustain higher diversities of
equivalent competitors than models in which these are not both localized, there
is debate as to whether this reflects merely equalizing effects or whether there
is also a stabilizing component. In this study, we explore how dispersal
limitation and nonspecific local competition influence the outcome of species
coexistence in communities driven by stochastic drift. We demonstrate that space
alone acts as a stabilizing factor in a continuous space model with local
dispersal and competition, as individuals of rare species on average experience
lower total neighborhood densities, causing per capita reproductive rates to
decrease systematically with increasing abundance. These effects prolong time to
extinction in a closed system and enhance species diversity in an open system
with constant immigration. Fundamentally, these stabilizing effects are obtained
when dispersal limitation interacts with local competition to generate
fluctuations in population growth rates. Thus this effect can be considered a
fluctuating mechanism similar to spatial or temporal storage effects, but
generated purely endogenously without requiring any exogenous environmental
variability or species dissimilarities.
PMID- 27609403
TI - The function of heparan sulfate during branching morphogenesis.
AB - Branching morphogenesis is a fundamental process in the development of diverse
epithelial organs such as the lung, kidney, liver, pancreas, prostate, salivary,
lacrimal and mammary glands. A unifying theme during organogenesis is the
importance of epithelial cell interactions with the extracellular matrix (ECM)
and growth factors (GFs). The diverse developmental mechanisms giving rise to
these epithelial organs involve many organ-specific GFs, but a unifying paradigm
during organogenesis is the regulation of GF activity by heparan sulfates (HS) on
the cell surface and in the ECM. This primarily involves the interactions of GFs
with the sulfated side-chains of HS proteoglycans. HS is one of the most diverse
biopolymers and modulates GF binding and signaling at the cell surface and in the
ECM of all tissues. Here, we review what is known about how HS regulates
branching morphogenesis of epithelial organs with emphasis on the developing
salivary gland, which is a classic model to investigate epithelial-ECM
interactions. We also address the structure, biosynthesis, turnover and function
of HS during organogenesis. Understanding the regulatory mechanisms that control
HS dynamics may aid in the development of therapeutic interventions for diseases
and novel strategies for tissue engineering and regenerative medicine.
PMID- 27609404
TI - Glomerular basement membrane heparan sulfate in health and disease: A regulator
of local complement activation.
AB - The glomerular basement membrane (GBM) is an essential component of the
glomerular filtration barrier. Heparan sulfate proteoglycans such as agrin are
major components of the GBM, along with alpha345(IV) collagen, laminin-521 and
nidogen. A loss of GBM heparan sulfate chains is associated with proteinuria in
several glomerular diseases and may contribute to the underlying pathology. As
the major determinants of the anionic charge of the GBM, heparan sulfate chains
have been thought to impart charge selectivity to the glomerular filtration, a
view challenged by the negligible albuminuria in mice that lack heparan sulfate
in the GBM. Recent studies provide increasing evidence that heparan sulfate
chains modulate local complement activation by recruiting complement regulatory
protein factor H, the major inhibitor of the alternative pathway in plasma.
Factor H selectively inactivates C3b bound to surfaces bearing host-specific
polyanions such as heparan sulfate, thus limiting complement activation on self
surfaces such as the GBM, which are not protected by cell-bound complement
regulators. We discuss mechanisms whereby the acquired loss of GBM heparan
sulfate can impair the local regulation of the alternative pathway, exacerbating
complement activation and glomerular injury in immune-mediated kidney diseases
such as membranous nephropathy and lupus nephritis.
PMID- 27609407
TI - Yellow fever outbreaks, vaccine shortages and the Hajj and Olympics: call for
global vigilance.
PMID- 27609406
TI - Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on
treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a
randomised, double-blind, placebo-controlled phase 3 trial.
AB - BACKGROUND: Benralizumab is a humanised, afucosylated, anti-interleukin-5
receptor alpha monoclonal antibody that induces direct, rapid, and nearly
complete depletion of eosinophils. We aimed to assess the efficacy and safety of
benralizumab as add-on therapy for patients with severe, uncontrolled asthma and
elevated blood eosinophil counts. METHODS: In this randomised, double-blind,
parallel-group, placebo-controlled, phase 3 study (CALIMA) undertaken at 303
sites in 11 countries, we enrolled patients aged 12-75 years with severe asthma
uncontrolled by medium-dosage to high-dosage inhaled corticosteroids plus long
acting beta2-agonists (ICS plus LABA) and a history of two or more exacerbations
in the previous year. Patients were randomly assigned (1:1:1) to receive 56 weeks
of benralizumab 30 mg every 4 weeks (Q4W), benralizumab 30 mg every 8 weeks (Q8W;
first three doses 4 weeks apart), or placebo (all subcutaneous injection).
Patients were stratified (2:1) by baseline blood eosinophil counts 300 cells per
MUL or greater and less than 300 cells per MUL, respectively. Patients and study
centre staff were masked to treatment allocation. The primary endpoint was annual
exacerbation rate ratio versus placebo for patients receiving high-dosage ICS
plus LABA with baseline blood eosinophils 300 cells per MUL or greater (intention
to-treat analysis). Key secondary endpoints were pre-bronchodilator forced
expiratory volume in 1 s (FEV1) and total asthma symptom score. This study is
registered with ClinicalTrials.gov, number NCT01914757. FINDINGS: Between Aug 21,
2013, and March 16, 2015, 2505 patients were enrolled, of whom 1306 patients were
randomised; 425 patients were randomly assigned to and received benralizumab 30
mg Q4W, 441 to benralizumab 30 mg Q8W, and 440 to placebo. 728 patients were
included in the primary analysis population. Benralizumab resulted in
significantly lower annual exacerbation rates with the Q4W regimen (rate 0.60
[95% CI 0.48-0.74], rate ratio 0.64 [95% CI 0.49-0.85], p=0.0018, n=241) and Q8W
regimen (rate 0.66 [95% CI 0.54-0.82], rate ratio 0.72 [95% CI 0.54-0.95],
p=0.0188, n=239) compared with placebo (rate 0.93 [95% CI 0.77-1.12], n=248).
Benralizumab also significantly improved pre-bronchodilator FEV1 (Q4W and Q8W)
and total asthma symptom score (Q8W only) in these patients. The most common
adverse events were nasopharyngitis (90 [21%] in the Q4W group, 79 [18%] in the
Q8W group, and 92 [21%] in the placebo group) and worsening asthma (61 [14%] in
the Q4W group, 47 [11%] in the Q8W group, and 68 [15%] in the group).
INTERPRETATION: Benralizumab significantly reduced annual exacerbation rates and
was generally well tolerated for patients with severe, uncontrolled asthma with
blood eosinophils 300 cells per MUL or greater. Our data further refine the
patient population likely to receive the greatest benefit from benralizumab
treatment. FUNDING: AstraZeneca and Kyowa Hakko Kirin.
PMID- 27609409
TI - Treatment for severe eosinophilic asthma-consistent effect of anti-interleukin-5
antibodies?
PMID- 27609408
TI - Efficacy and safety of benralizumab for patients with severe asthma uncontrolled
with high-dosage inhaled corticosteroids and long-acting beta2-agonists
(SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.
AB - BACKGROUND: Eosinophilia is associated with worsening asthma severity and
decreased lung function, with increased exacerbation frequency. We assessed the
safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5
receptor alpha that depletes eosinophils by antibody-dependent cell-mediated
cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.
METHODS: We did a randomised, double-blind, parallel-group, placebo-controlled
phase 3 study at 374 sites in 17 countries. We recruited patients (aged 12-75
years) with a physician-based diagnosis of asthma for at least 1 year and at
least two exacerbations while on high-dosage inhaled corticosteroids and long
acting beta2-agonists (ICS plus LABA) in the previous year. Patients were
randomly assigned (1:1:1) by an interactive web-based voice response system to
benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three
doses every 4 weeks) or placebo Q4W for 48 weeks as add on to their standard
treatment. Patients were stratified 2:1 according to blood eosinophil counts of
at least 300 cells per MUL and less than 300 cells per MUL. All patients and
investigators involved in patient treatment or clinical assessment were masked to
treatment allocation. The primary endpoint was annual exacerbation rate ratio
versus placebo, and key secondary endpoints were prebronchodilator forced
expiratory volume in 1 s (FEV1) and total asthma symptom score at week 48, for
patients with blood eosinophil counts of at least 300 cells per MUL. Efficacy
analyses were by intention to treat (based on the full analysis set); safety
analyses included patients according to study drug received. This study is
registered with ClinicalTrials.gov, number NCT01928771. FINDINGS: Between Sept
19, 2013, and March 16, 2015, 2681 patients were enrolled, 1205 of whom met the
study criteria and were randomly assigned: 407 to placebo, 400 to benralizumab 30
mg Q4W, and 398 to benralizumab 30 mg Q8W. 267 patients in the placebo group, 275
in the benralizumab 30 mg Q4W group, and 267 in the benralizumab 30 mg Q8W group
had blood eosinophil counts at least 300 cells per MUL and were included in the
primary analysis population. Compared with placebo, benralizumab reduced the
annual asthma exacerbation rate over 48 weeks when given Q4W (rate ratio 0.55,
95% CI 0.42-0.71; p<0.0001) or Q8W (0.49, 0.37-0.64; p<0.0001). Both benralizumab
dosing regimens significantly improved prebronchodilator FEV1 in patients at week
48 compared with placebo (least-squares mean change from baseline: Q4W group
0.106 L, 95% CI 0.016-0.196; Q8W group 0.159 L, 0.068-0.249). Compared with
placebo, asthma symptoms were improved by the Q8W regimen (least-squares mean
difference -0.25, 95% CI -0.45 to -0.06), but not the Q4W regimen (-0.08, -0.27
to 0.12). The most common adverse events were worsening asthma (105 [13%] of 797
benralizumab-treated patients vs 78 [19%] of 407 placebo-treated patients) and
nasopharyngitis (93 [12%] vs 47 [12%]). INTERPRETATION: These results confirm the
efficacy and safety of benralizumab for patients with severe asthma and elevated
eosinophils, which are uncontrolled by high-dosage ICS plus LABA, and provide
support for benralizumab to be an additional option to treat this disease in this
patient population. FUNDING: AstraZeneca and Kyowa Hakko Kirin.
PMID- 27609411
TI - Assessing the diversity, host-specificity and infection patterns of apicomplexan
parasites in reptiles from Oman, Arabia.
AB - Understanding the processes that shape parasite diversification, their
distribution and abundance provides valuable information on the dynamics and
evolution of disease. In this study, we assessed the diversity, distribution,
host-specificity and infection patterns of apicomplexan parasites in amphibians
and reptiles from Oman, Arabia. Using a quantitative PCR approach we detected
three apicomplexan parasites (haemogregarines, lankesterellids and sarcocystids).
A total of 13 haemogregarine haplotypes were identified, which fell into four
main clades in a phylogenetic framework. Phylogenetic analysis of six new
lankesterellid haplotypes revealed that these parasites were distinct from, but
phylogenetically related to, known Lankesterella species and might represent new
taxa. The percentage of infected hosts (prevalence) and the number of
haemogregarines in the blood (parasitaemia) varied significantly between gecko
species. We also found significant differences in parasitaemia between
haemogregarine parasite lineages (defined by phylogenetic clustering of
haplotypes), suggesting differences in host-parasite compatibility between these
lineages. For Pristurus rupestris, we found significant differences in
haemogregarine prevalence between geographical areas. Our results suggest that
host ecology and host relatedness may influence haemogregarine distributions and,
more generally, highlight the importance of screening wild hosts from remote
regions to provide new insights into parasite diversity.
PMID- 27609410
TI - Childhood autism spectrum disorders and exposure to nitrogen dioxide, and
particulate matter air pollution: A review and meta-analysis.
AB - BACKGROUND AND OBJECTIVE: Genetic and environmental factors have been recognized
to play an important role in autism. The possibility that exposure to outdoor air
pollution increases the risk of autism spectrum disorder (ASD) has been an
emerging area of research. Herein, we present a systematic review, and meta
analysis of published epidemiological studies that have investigated these
associations. METHODS: We undertook a comprehensive search strategy to identify
studies that investigated outdoor air pollution and autism in children. Overall,
seven cohorts and five case-control studies met our inclusion criteria for the
meta-analysis. We summarized the associations between exposure to air pollution
and ASD based on the following critical exposure windows: (i) first, second and
third trimester of pregnancy, (ii) entire pregnancy, and (iii) postnatal period.
Random effects meta-analysis modeling was undertaken to derive pooled risk
estimates for these exposures across the studies. RESULTS: The meta-estimates for
the change in ASD associated with a 10MUg/m3 increase in exposure in PM2.5 and 10
ppb increase in NO2 during pregnancy were 1.34 (95% CI:0.83, 2.17) and 1.05 (95%
CI:0.99, 1.11), respectively. Stronger associations were observed for exposures
received after birth, but these estimates were unstable as they were based on
only two studies. O3 exposure was weakly associated with ASD during the third
trimester of pregnancy and during the entire pregnancy, however, these estimates
were also based on only two studies. CONCLUSION: Our meta-analysis support the
hypothesis that exposure to ambient air pollution is associated with an increased
risk of autism. Our findings should be interpreted cautiously due to relatively
small number of studies, and several studies were unable to control for other key
risk factors.
PMID- 27609412
TI - Towards an exposure-dependent model of post-traumatic stress: longitudinal course
of post-traumatic stress symptomatology and functional impairment after the 2011
Oslo bombing.
AB - BACKGROUND: Our understanding of the dynamics of post-traumatic stress
symptomatology and its link to functional impairment over time is limited.
METHOD: Post-traumatic stress symptomatology (Post-traumatic Checklist, PCL) was
assessed three times in 1-year increments (T1, T2, T3) following the Oslo bombing
of 22 July, 2011, in directly (n = 257) and indirectly exposed (n = 2223)
government employees, together with demographics, measures of exposure and work
and social adjustment. The dynamics of post-traumatic stress disorder symptom
cluster interplay were examined within a structural equation modelling framework
using a cross-lagged autoregressive panel model. RESULTS: Intrusions at T1 played
a prominent role in predicting all symptom clusters at T2 for the directly
exposed group, exhibiting especially strong cross-lagged relationships with
avoidance and anxious arousal. For the indirectly exposed group, dysphoric
arousal at T1 played the most prominent role in predicting all symptom clusters
at T2, exhibiting a strong relationship with emotional numbing. Emotional numbing
seemed to be the main driver behind prolonged stress at T3 for both groups.
Functional impairment was predominately associated with dysphoric arousal and
emotional numbing in both groups. CONCLUSIONS: For directly exposed individuals,
memories of the traumatic incident and the following intrusions seem to drive
their post-traumatic stress symptomatology. However, as these memories lose their
potency over time, a sequela of dysphoric arousal and emotional numbing similar
to the one reported by the indirectly exposed individuals seems to be the main
driver for prolonged post-traumatic stress and functional impairment. Findings
are discussed using contemporary models within an exposure-dependent perspective
of post-traumatic stress.
PMID- 27609414
TI - Statistical concerns in the development of a prediction model.
PMID- 27609413
TI - The role of contrast-enhanced ultrasound in the classification of CT
indeterminate renal lesions.
AB - OBJECTIVE: Focal renal lesions are common incidental findings on computed
tomography (CT). For lesions with a cystic appearance, the Bosniak classification
system has enabled an important separation of benign and (potentially) malignant
cysts, giving a practical guide for management. The purpose of this study was to
evaluate contrast-enhanced ultrasound (CEUS) as a problem-solving modality for
classification of indeterminate renal lesions detected with CT. MATERIALS AND
METHODS: In total, 140 consecutive patients with 148 indeterminate renal lesions
were examined with ultrasound combined with CEUS (81 men and 59 women with mean
age 63.8 years). RESULTS: Altogether, 146 lesions were classified by CEUS in
categories according to the Bosniak classification system, or as solid lesions.
Mean lesion diameter was 30 mm (range 5-166 mm). Nine lesions were classified as
category I, 32 as category II and 59 as category IIF ("non-surgical lesions"). 48
IIF cysts were followed for a minimum of 2 years (mean 4 years and 8 months):
three lesions were upgraded to category III (6%) and 45 were stable category. 19
lesions had a more complex cystic appearance: 12 were classified as category III
and seven as category IV cysts. 27 lesions were diagnosed as solid, enhancing
tumors. In total, 25 patients with lesions of category III, IV and solid
("surgical lesions") underwent renal surgery, with malignancy diagnosed in 18.
CONCLUSION: In the common setting of indeterminate renal lesions incidentally
detected with a CT exam, CEUS has the potential to classify lesions into "non
surgical" and "surgical" categories, providing a platform for urological decision
making, while avoiding radiation exposure.
PMID- 27609415
TI - Child-directed and nutrition-focused marketing cues on food packaging: links to
nutritional content.
AB - OBJECTIVE: We tested whether the presence of both child-targeted and nutrition
focused (i.e. parent-targeted) marketing cues on food packaging was associated
with the nutritional content of these products. DESIGN: We conducted a
quantitative content analysis of 403 food packages chosen randomly from the
supermarket's online portal along with all products (n 312) from the cereal aisle
in a supermarket from the Southeastern USA. We examined main and interaction
effects for cues on nutritional content (e.g. energy density, sugar, sodium,
fibre). SETTING: A regional supermarket chain in the Southeastern USA. RESULTS:
Tests of main effects indicated that increased presence of nutritional cues was
linked to more nutritious content (e.g. less sugar, less saturated fat, more
fibre) while the increased presence of child-targeted cues was uniformly
associated with less nutritious content (e.g. more sugar, less protein, less
fibre). Among the interaction effects, results revealed that products with
increased nutrition-focused and child-targeted cues were likely to contain
significantly more sugar and less protein than other products. CONCLUSIONS:
Products that seek to engage children with their packaging in the supermarket are
significantly less nutritious than foods that do not, while product packages that
suggest nutritional benefits have more nutritious content. More importantly, the
study provides evidence that those products which try to engage both child and
parent consumers are significantly less healthy in crucial ways (e.g. more sugar,
less fibre) than products that do not.
PMID- 27609416
TI - Association Between Paraoxonase 2 Ser311Cys Polymorphism and Coronary Heart
Disease Risk: A Meta-Analysis.
AB - BACKGROUND The relationship between coronary heart disease (CHD) and the
paraoxonase 2 (PON2) Ser311Cys polymorphism has received much attention. We
conducted a meta-analysis on the results from published case-control studies
examining this relation. MATERIAL AND METHODS A literature search was performed
using PubMed and ISI Web of Knowledge databases until October 2015. Odds ratios
(OR) and 95% confidence intervals (CI) were calculated using Stata version 11.0
software. Data were pooled using the random-effects model. RESULTS Nine studies
were eligible for statistical analysis and included a total of 5278 participants.
The results did not support an association between the Ser311Cys polymorphism and
CHD in the overall populations (Asians, Caucasians, and a Hispanic mixed
population) under dominant (OR 1.07; 95% CI 0.91-1.28; Pz=0.413), recessive (OR
1.19; 95% CI 0.72-1.95; Pz=0.500), homozygote (OR 1.20; 95% CI 0.71-2.03;
Pz=0.489), and allelic comparison (OR 1.08; 95% CI 0.91-1.28; Pz=0.390) models.
However, in subgroup analysis according to ethnicity, we found that the Ser311Cys
polymorphism was associated with CHD risk in Caucasians under recessive (OR 2.08;
95% CI 1.30-3.34; Pz=0.002) and homozygote (OR 2.16; 95% CI 1.33-3.50; Pz=0.002)
models. Subgroup analysis indicated no significant association of this
polymorphism with CHD in either Asian or Hispanic populations. CONCLUSIONS The
PON2 Ser311Cys polymorphism is associated with CHD risk in Caucasians, but there
is no association between this polymorphism and CHD in Asians or Hispanic
populations.
PMID- 27609417
TI - Synthesis and evaluation of L-cystathionine as a standard for amino acid
analysis.
AB - L-Cystathionine is a key nonprotein amino acid related to metabolic conditions.
The quantitative determination of L-cystathionine in physiological fluids by
amino acid analysis is important for clinical diagnosis; however, certified
reference material for L-cystathionine with satisfactory purity, content, and
quantity has been unavailable until recently. Consequently, a practical and
simple method for the preparation of L-cystathionine was examined, which involves
thioalkylation of N-tert-butoxycarbonyl-L-cysteine tert-butyl ester, derived from
L-cystine, with (2S)-2-(tert-butoxycarbonyl)amino-4-iodobutanoic acid tert-butyl
ester, derived from L-aspartic acid, to obtain L-cystathionine with protecting
groups, followed by single-step deprotection under mild conditions. This method
produces L-cystathionine in high purity (99.4%) and having sufficient percentage
content according to amino acid analysis, which could be used as a standard for
the amino acid analysis of physiological fluids.
PMID- 27609418
TI - Willingness to use hospice care among caregivers of Latino patients in the United
States-Mexico border region.
AB - OBJECTIVE: Hospice is an important method of promoting quality end-of-life (EoL)
care, yet its utilization is relatively low in underserved populations. The
unique characteristics of a border community-such as a lack of healthcare
resources and cultural integration-impact EoL decision making. The aim of our
study was to assess the willingness to use hospice care services and its
predictors among family caregivers of Latino patients in the United States (U.S.)
Mexico border region of Southern California. METHOD: This study analyzes
secondary data from a home health agency in the U.S.-Mexico border region.
Quantitative data were collected via a face-to-face interview with 189 caregivers
of patients enrolled in the agency. Bivariate tests and logistic regression were
employed to address our study objectives. RESULTS: The majority (83%) of family
caregivers were willing to use hospice services for their loved ones. The factors
impacting willingness to use hospice services included the primary language of
the caregiver (OR = 6.30, CI 95% = 1.68, 23.58); trust in doctors to make the
right decisions (OR = 3.77, CI 95% = 1.05, 13.57); and the belief that using
hospice care means giving up on life (OR = 0.52, CI 95% = 0.30; 0.88). Caregivers
who trusted doctors to make the best decisions for their loved ones and English
speaking caregivers were more willing to utilize hospice services, while
caregivers who held a strong belief that hospice care means giving up on life
were less likely to consider using hospice care for their loved ones.
SIGNIFICANCE OF RESULTS: The willingness of family caregivers to use hospice
services for their loved ones is influenced by cultural perspectives about
hospice care. As the importance of family involvement in EoL care planning has
been highlighted, family caregivers' beliefs about hospice care services need to
be addressed within their particular cultural context.
PMID- 27609419
TI - Crystal structures of the UDP-diacylglucosamine pyrophosphohydrase LpxH from
Pseudomonas aeruginosa.
AB - Lipid A (also known as endotoxin) is the hydrophobic portion of
lipopolysaccharides. It is an essential membrane component required for the
viability of gram-negative bacteria. The enzymes involved in its biosynthesis are
attractive targets for the development of novel antibiotics. LpxH catalyzes the
fourth step of the lipid A biosynthesis pathway and cleaves the pyrophosphate
bond of UDP-2,3-diacylglucosamine to yield 2,3-diacylglucosamine 1-phosphate
(lipid X) and UMP. Here we present the structures of LpxH from Pseudomonas
aeruginosa (PaLpxH). PaLpxH consists of two domains: a catalytic domain that is
homologous to the metallophosphoesterases and a helical insertion domain. Lipid X
was captured in the crevice between these two domains, with its phosphate group
facing the dinuclear metal (Mn(2+)) center and two acyl chains buried in the
hydrophobic cavity. The structures reveal that a large conformational change
occurs at the lipid X binding site surface upon the binding/release of the
product molecule. Based on these observations, we propose a novel model for lipid
X embedding, which involves the scissor-like movement of helix alpha6, resulting
in the release of lipid X into the lipid bilayer.
PMID- 27609420
TI - Multi-species Identification of Polymorphic Peptide Variants via Propagation in
Spectral Networks.
AB - Peptide and protein identification remains challenging in organisms with poorly
annotated or rapidly evolving genomes, as are commonly encountered in
environmental or biofuels research. Such limitations render tandem mass
spectrometry (MS/MS) database search algorithms ineffective as they lack
corresponding sequences required for peptide-spectrum matching. We address this
challenge with the spectral networks approach to (1) match spectra of orthologous
peptides across multiple related species and then (2) propagate peptide
annotations from identified to unidentified spectra. We here present algorithms
to assess the statistical significance of spectral alignments (Align-GF), reduce
the impurity in spectral networks, and accurately estimate the error rate in
propagated identifications. Analyzing three related Cyanothece species, a model
organism for biohydrogen production, spectral networks identified peptides from
highly divergent sequences from networks with dozens of variant peptides,
including thousands of peptides in species lacking a sequenced genome. Our
analysis further detected the presence of many novel putative peptides even in
genomically characterized species, thus suggesting the possibility of gaps in our
understanding of their proteomic and genomic expression. A web-based pipeline for
spectral networks analysis is available at http://proteomics.ucsd.edu/software.
PMID- 27609421
TI - TNIP2 is a Hub Protein in the NF-kappaB Network with Both Protein and RNA
Mediated Interactions.
AB - The NF-kappaB family of transcription factors is pivotal in controlling cellular
responses to environmental stresses; abnormal nuclear factor kappa-light-chain
enhancer of activated B cells (NF-kappaB) signaling features in many autoimmune
diseases and cancers. Several components of the NF-kappaB signaling pathway have
been reported to interact with the protein TNIP2 (also known as ABIN2), and TNIP2
can both positively and negatively regulate NF-kappaB- dependent transcription of
target genes. However, the function of TNIP2 remains elusive and the cellular
machinery associating with TNIP2 has not been systematically defined. Here we
first used a broad MudPIT/Halo Affinity Purification Mass Spectrometry (AP-MS)
approach to map the network of proteins associated with the NF-kappaB
transcription factors, and establish TNIP2 as an NF-kappaB network hub protein.
We then combined AP-MS with biochemical approaches in a more focused study of
truncated and mutated forms of TNIP2 to map protein associations with distinct
regions of TNIP2. NF-kappaB interacted with the N-terminal region of TNIP2. A
central region of TNIP2 interacted with the endosomal sorting complex ESCRT-I via
its TSG101 subunit, a protein essential for HIV-1 budding, and a single point
mutant in TNIP2 disrupted this interaction. The major gene ontology category for
TNIP2 associated proteins was mRNA metabolism, and several of these associations,
like KHDRBS1, were lost upon depletion of RNA. Given the major association of
TNIP2 with mRNA metabolism proteins, we analyzed the RNA content of affinity
purified TNIP2 using RNA-Seq. Surprisingly, a specific limited number of mRNAs
was associated with TNIP2. These RNAs were enriched for transcription factor
binding, transcription factor cofactor activity, and transcription regulator
activity. They included mRNAs of genes in the Sin3A complex, the Mediator
complex, JUN, HOXC6, and GATA2. Taken together, our findings suggest an expanded
role for TNIP2, establishing a link between TNIP2, cellular transport machinery,
and RNA transcript processing.
PMID- 27609423
TI - Rate of biological invasions is lower in coastal marine protected areas.
AB - Marine biological invasions threaten biodiversity worldwide. Here we explore how
Marine Protected areas, by reducing human use of the coast, confer resilience
against the introduction of non-indigenous species (NIS), using two very
different Pacific islands as case studies for developing and testing mathematical
models. We quantified NIS vectors and promoters on Vancouver (Canada) and Moorea
(French Polynesia) islands, sampled and barcoded NIS, and tested models at
different spatial scales with different types of interaction among vectors and
between marine protection and NIS frequency. In our results NIS were negatively
correlated with the dimension of the protected areas and the intensity of the
protection. Small to medium geographical scale protection seemed to be efficient
against NIS introductions. The likely benefit of MPAs was by exclusion of
aquaculture, principally in Canada. These results emphasize the importance of
marine protected areas for biodiversity conservation, and suggest that small or
medium protected zones would confer efficient protection against NIS
introduction.
PMID- 27609424
TI - Cost-utility analysis of ledipasvir/sofosbuvir for the treatment of genotype 1
chronic hepatitis C in Japan.
AB - OBJECTIVE: Hepatitis C is the result of a ribonucleic acid (RNA) virus (hepatitis
C virus; HCV). The Japan Society of Hepatology (JSH) estimated that 1.5-2 million
people in Japan carry HCV. Six major HCV genotypes (GT) and a large number of
subtypes have been described in the literature. In Japan, around 70% to 80% of
people are infected with HCV genotype 1b. The progress of the disease primarily
affects the liver and may lead to liver cirrhosis, hepatocellular carcinoma (HCC)
and death. Sofosbuvir (SOF) is a nucleotide analogue NS5B inhibitor and
ledipasvir (LDV) is an inhibitor of the HCV NS5A protein. They are combined in a
single tablet regimen for the treatment of GT1 patients and resulted in sustained
virological response (SVR) above 94% in large phase III trials. This analysis
assesses the cost-utility of LDV/SOF in GT1 patients in Japan. RESEARCH DESIGN
AND METHODS: A cohort of 10,000 patients was followed through a Markov model
until they reached 100 years of age. GT1 treatment-naive and experienced, non
cirrhotic and cirrhotic patients were studied separately. LDV/SOF was compared to
several treatment regimens containing pegylated interferon (PEGIFN), telaprevir
(TVR), simeprevir (SMV), daclatasvir (DCV), asunaprevir (ASV) and ribavirin
(RBV). Discount rates of 2% were applied to costs and outcomes according to the
Japanese guidelines. RESULTS: LDV/SOF was cost-effective against most comparators
with incremental cost-effectiveness ratios (ICERs) below JPY 5,000,000. By
applying a societal perspective, LDV/SOF was the dominant treatment strategy in
all cases. Moreover, LDV/SOF reduced the number of cases of advanced liver
disease. These results were robust to sensitivity analyses. CONCLUSIONS: LDV/SOF
was cost-effective compared to most of the currently recommended treatments.
Furthermore, LDV/SOF extends treatments to HCV-infected patients who are
ineligible for interferon and RBV-based regimens. LDV/SOF thus has the potential
to help reduce the burden of HCV in Japan.
PMID- 27609425
TI - ?Nalmefene-time for last orders?
PMID- 27609422
TI - Novel Aquaporin Regulatory Mechanisms Revealed by Interactomics.
AB - PIP1;2 and PIP2;1 are aquaporins that are highly expressed in roots and bring a
major contribution to root water transport and its regulation by hormonal and
abiotic factors. Interactions between cellular proteins or with other
macromolecules contribute to forming molecular machines. Proteins that
molecularly interact with PIP1;2 and PIP2;1 were searched to get new insights
into regulatory mechanisms of root water transport. For that, a immuno
purification strategy coupled to protein identification and quantification by
mass spectrometry (IP-MS) of PIPs was combined with data from the literature, to
build thorough PIP1;2 and PIP2;1 interactomes, sharing about 400 interacting
proteins. Such interactome revealed PIPs to behave as a platform for recruitment
of a wide range of transport activities and provided novel insights into
regulation of PIP cellular trafficking by osmotic and oxidative treatments. This
work also pointed a role of lipid signaling in PIP function and enhanced our
knowledge of protein kinases involved in PIP regulation. In particular we show
that 2 members of the receptor-like kinase (RLK) family (RKL1 (At1g48480) and
Feronia (At3g51550)) differentially modulate PIP activity through distinct
molecular mechanisms. The overall work opens novel perspectives in understanding
PIP regulatory mechanisms and their role in adjustment of plant water status.
PMID- 27609426
TI - Understanding observational studies.
AB - The development of evidence-based medicine has encouraged clinicians to consider
the best available evidence when making clinical decisions, individualised for
the patient.(1,2) A hierarchy of levels of evidence about therapy is described,
with the highest being meta-analyses and large, well-designed randomised
controlled trials.(3-5) Lower down the hierarchy are observational studies, a
group that includes cohort, case-control and cross-sectional studies. Here we
describe the benefits and limitations of observational studies, and how to assess
their quality.
PMID- 27609427
TI - Epidemiological profile and genetic diversity of sapoviruses (SaVs) identified in
children suffering from acute gastroenteritis in Pune, Maharashtra, Western
India, 2007-2011.
AB - Sapoviruses (SaVs) are responsible for sporadic cases and outbreaks of acute
gastroenteritis. Despite this, few studies in India have focused on the
epidemiological investigation of SaV in cases of acute gastroenteritis. The aim
of this study was to understand the molecular epidemiology, genetic diversity and
clinical impact of SaV in diarrhoeic children from Pune, Western India. Between
2007 and 2011, a total of 985 faecal samples from diarrhoeic cases and non
diarrhoeic controls were collected and examined for the presence of SaV by nested
RT-PCR. SaV was detected in 2.7% (21/778) of the cases and 1.9% (4/207) of the
controls. We observed that the majority of SaV mono-infections caused severe
gastroenteritis (67%) with clinical manifestations of diarrhoea (100%), vomiting
(73%) and dehydration (80%). All known human SaV genogroups were detected in the
study. At least eight genotypes were identified from cases and controls.
Genogroups GIV and GV, along with genotypes GI.5, GII.4 and GII.6, were
discovered for the first time in India. Two GII.4 study strains were found to be
98.5-99% identical, having a novel intra-genogroup recombinant (GII.1/GII.4)
recently reported from the Philippines, suggesting probable evidence of
recombination. The circulation pattern of SaV genotypes varied during the study
period, with GII.1 being predominant in 2007 and 2009, GIV.1 in 2008, and GV.1 in
2011.
PMID- 27609428
TI - Effects of electric field on micro-scale flame properties of biobutanol fuel.
AB - With the increasing need of smaller power sources for satellites, energy systems
and engine equipment, microcombustion pose a potential as alternative power
source to conventional batteries. As the substitute fuel source for gasoline,
biobutanol shows more promising characteristics than ethanol. In this study, the
diffusion microflame of liquid biobutanol under electric field have been examined
through in-lab experiment and numerical simulation. It is found that traditional
gas jet diffusion flame theory shows significant inconsistency with the
experimental results of micro scale flame in electric field. The results suggest
that with the increase of electric field intensity, the quenching flow rate
decrease first and increase after it reach its minimum, while the flame height
and highest flame temperature increase first and drop after its peak value. In
addition, it was also observed that the flame height and highest temperature for
smaller tube can reach its maximum faster. Therefore, the interaction between
microscale effect and electric field plays a significant role on understanding
the microcombustion of liquid fuel. Therefore, FLUENT simulation was adopted to
understand and measure the impacts of microflame characteristic parameters. The
final numerical results are consistent with the experimental data and show a high
reliability.
PMID- 27609429
TI - Pressure thresholds and stiffness on the plantar surface of the human foot.
AB - A methodology to assess Pressure Discomfort Thresholds (PDT), Pressure Pain
Thresholds (PPT) and tissue stiffness on the plantar surface of the foot was
developed. Ten male and 10 female participants volunteered for the study. Foot
landmarks were used to create a standardised grid-type template of 95 points. For
each test point, PPT and PDT values were obtained, and stiffness was calculated
for each of the 20 participants. Cluster analyses were performed to determine the
regions of similarity for the three dependent variables, PPT, PDT and stiffness.
Moran's-I-index was used to determine the spatial auto correlations. The use of k
means clustering showed five distinct clusters while the three dependent
variables showed strong correlations to each other. Morisita's similarity index
was used to check the similarity of the grid among all participants. Both male
and female participants showed a Morisita's index greater than 0.7 confirming the
reliability of the foot template. Practitioner Summary: Pressure Discomfort
thresholds (PPT), Pressure pain thresholds (PPT) and tissue stiffness were
evaluated at 95 points on the plantar surface of the foot. The PPT and related
PDT map are useful to design the footbeds of shoes. Based on the data collected,
five distinct clusters of locations were identified.
PMID- 27609430
TI - 2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the
Management of Atrial Fibrillation.
AB - The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines
Committee provides periodic reviews of new data to produce focused updates that
address clinically important advances in AF management. This 2016 Focused Update
deals with: (1) the management of antithrombotic therapy for AF patients in the
context of the various clinical presentations of coronary artery disease; (2)
real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of
antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4)
digoxin as a rate control agent; (5) perioperative anticoagulation management;
and (6) AF surgical therapy including the prevention and treatment of AF after
cardiac surgery. The recommendations were developed with the same methodology
used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using
the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
standards, individual studies and literature were reviewed for quality and bias;
the literature review process and evidence tables are included in the
Supplementary Material, and on the CCS Web site. The section on concomitant AF
and coronary artery disease was developed in collaboration with the CCS
Antiplatelet Guidelines Committee. Details of the updated recommendations are
presented, along with their background and rationale. This document is linked to
an updated summary of all CCS AF Guidelines recommendations, from 2010 to the
present 2016 Focused Update.
PMID- 27609432
TI - Complete genome sequencing and comparative analyses of broad-spectrum
antimicrobial-producing Micromonospora sp. HK10.
AB - Micromonospora genus produces >700 bioactive compounds of medical relevance. In
spite of its ability to produce high number of bioactive compounds, no genome
sequence is available with comprehensive secondary metabolite gene clusters
analysis for anti-microbial producing Micromonospora strains. Thus, here we
contribute the full genome sequence of Micromonospora sp. HK10 strain, which has
high antibacterial activity against several important human pathogens like,
Mycobacterium abscessus, Mycobacterium smegmatis, Bacillus subtillis,
Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella and
Escherichia coli. We have generated whole genome sequence data of Micromonospora
sp. HK10 strain using Illumina NexSeq 500 sequencing platform (2*150bp paired end
library) and assembled it de novo. The sequencing of HK10 genome enables
identification of various genetic clusters associated with known- and probably
unknown- antimicrobial compounds, which can pave the way for new antimicrobial
scaffolds.
PMID- 27609431
TI - Enhancing the Surface Sensitivity of Metallic Nanostructures Using Oblique-Angle
Induced Fano Resonances.
AB - Surface sensitivity is an important factor that determines the minimum amount of
biomolecules detected by surface plasmon resonance (SPR) sensors. We propose the
use of oblique-angle-induced Fano resonances caused by two-mode coupling or three
mode coupling between the localized SPR mode and long-range surface plasmon
polariton modes to increase the surface sensitivities of silver capped nanoslits.
The results indicate that the coupled resonance between the split SPR (-kSPR) and
cavity modes (two-mode coupling) has a high wavelength sensitivity for small
angle incidence (2 degrees ) due to its short decay length. Additionally, three
mode coupling between the split SPR (-kSPR), substrate (+kSub) and cavity modes
has a high intensity sensitivity for large-angle incidence due to its short decay
length, large resonance slope and enhanced transmission intensity. Compared to
the wavelength measurement, the intensity measurement has a lower detectable
(surface) concentration below 1 ng/ml (0.14 pg/mm(2)) and is reduced by at least
3 orders of magnitude. In addition, based on the calibration curve and current
system noise, a theoretical detection limit of 2.73 pg/ml (0.38 fg/mm(2)) can be
achieved. Such a surface concentration is close to that of prism-based SPR with
phase measurement (0.1-0.2 fg/mm(2) under a phase shift of 5 mdeg).
PMID- 27609433
TI - Cardiologists and diabetes.
PMID- 27609434
TI - Role of endocardial septal ablation in the treatment of hypertrophic obstructive
cardiomyopathy.
AB - Septal reduction therapy is accepted as a first therapeutic option for
symptomatic drug-resistant hypertrophic obstructive cardiomyopathy (HOCM).
Although, surgical septal myectomy is the gold standard method, alcohol septal
ablation is a well-studied alternative approach in the patients with suitable
anatomy. Endocardial septal ablation (ESA) therapy was relatively new defined
modality and outcomes of the procedure were not clearly elucidated yet. We aimed
to review the clinical aspects of ESA procedure and provide some historical
background.
PMID- 27609435
TI - Non-coronary abnormalities of the left heart: CT angiography findings.
AB - Cardiac computed tomography (CT) is most commonly performed for the evaluation of
the coronary arteries; however, non-coronary cardiac pathologies are frequently
detected on these scans. In cases where magnetic resonance imaging cannot be
used, cardiac CT can serve as the first-line imaging modality to evaluate many
non-coronary cardiac pathologies. In this article, we discuss congenital non
coronary abnormalities of the left heart and their cardiac CT imaging features.
PMID- 27609436
TI - IgG4-related aortitis mimicking intramural hematoma.
PMID- 27609437
TI - Polycystic ovary syndrome and arrhythmic risk: the role of comorbidities and the
prevalence of interatrial block.
PMID- 27609438
TI - Author's Reply.
PMID- 27609439
TI - A pilot study on salt taste sensitivity threshold in Turkish young adults.
PMID- 27609440
TI - A possible mechanism of spontaneous coronary dissection: coronary artery ectasia.
PMID- 27609441
TI - Social representation of "music" in young adults: a cross-cultural study.
AB - OBJECTIVE: This study was aimed to explore perceptions of and reactions to music
in young adults (18-25 years) using the theory of social representations (TSR).
DESIGN: The study used a cross-sectional survey design and included participants
from India, Iran, Portugal, USA and UK. Data were analysed using various
qualitative and quantitative methods. STUDY SAMPLE: The study sample included 534
young adults. RESULTS: The Chi-square analysis showed significant differences
between the countries regarding the informants' perception of music. The most
positive connotations about music were found in the responses obtained from
Iranian participants (82.2%), followed by Portuguese participants (80.6%), while
the most negative connotations about music were found in the responses obtained
from Indian participants (18.2%), followed by Iranian participants (7.3%). The
participants' responses fell into 19 main categories based on their meaning;
however, not all categories were found in all five countries. The co-occurrence
analysis results generally indicate that the category "positive emotions or
actions" was the most frequent category occurring in all five countries.
CONCLUSIONS: The results indicate that music is generally considered to bring
positive emotions for people within these societies, although a small percentage
of responses indicate some negative consequences of music.
PMID- 27609442
TI - Tract-Specific Diffusion Tensor Imaging Reveals Laterality of Neurological
Symptoms in Patients with Cervical Compression Myelopathy.
AB - BACKGROUND: Patients with cervical compression myelopathy (CCM) generally present
bilateral neurological symptoms in their extremities. However, a substantial
portion of patients with CCM exhibit laterality of neurological symptoms. The aim
of this study was to assess the correlation between intrinsic structural damage
and laterality of symptoms using spinal cord diffusion tensor imaging (DTI) of
the corticospinal tract. METHODS: We enrolled 10 healthy volunteers and 40
patients with CCM in this study. We evaluated motor function using the American
Spinal Injury Association (ASIA) motor score for left and right extremities. For
DTI acquisitions, a 3.0-T magnetic resonance imaging system with diffusion
weighted spin-echo sequence was used. Regions-of-interest in the lateral column
tracts were determined. We determined the correlations between fractional
anisotropy (FA) and ASIA motor scores. An FA asymmetry index was calculated using
left and right regions-of-interest. RESULTS: Four patients exhibited laterality
of symptoms in their extremities, for which left and right ASIA scores correlated
moderately with FA in the left and right lateral columns, respectively (left: rho
= 0.64, P < 0.001; right: rho = 0.67, P < 0.001). The area under the receiver
operator characteristic curve showed that the FA asymmetry index indicated
laterality of symptoms. CONCLUSIONS: Using tract-specific DTI, we demonstrated
that microstructural damages in the left and right corticospinal tracts
correlated with corresponding neurological symptoms in the ipsilateral side and
the FA asymmetry index could indicate laterality in neurological symptoms of
patients with CCM.
PMID- 27609443
TI - Angiographic Characteristics and Endovascular Treatment of Anterior Cerebral
Artery A1 Segment Aneurysms.
AB - OBJECTIVE: This report aimed to review the angiographic characteristics and
evaluate the safety and feasibility of endovascular treatment of A1 aneurysms.
METHODS: Nineteen ruptured and 13 unruptured A1 aneurysms treated endovascularly
were evaluated in this study. The angiographic and clinical records were
retrospectively reviewed. RESULTS: Endovascular treatments were successfully
applied in all 32 aneurysms. Conventional coiling was performed in 24 aneurysms,
stent-assisted coiling in 7, and solo stenting in 1. The immediate angiographic
result was 1 aneurysm in 15, two aneurysms in 10, and 3 in 7 aneurysms according
to the Raymond grade. Intraoperative rupture was detected in 1 case without
clinical consequence, and no other procedure-related complication occurred.
Angiographic follow-up (mean, 12 months; range, 2-42 months) of 25 aneurysms
showed total occlusion in 20, improvement in 1, stability in 3, and recurrence in
1. The only recurrence was detected in a case treated using conventional coiling,
and it was retreated with stent-assisted coiling. Clinical follow-up (mean, 25
months; range, 6-93 months) was available in 24 of 30 patients, and the modified
Rankin Scale score was 0-1 in 22 patients. CONCLUSIONS: Endovascular treatment is
technically feasible and safe for A1 aneurysms.
PMID- 27609445
TI - Management of Challenging Hydrocephalus Scenarios: Clinical Perspective.
PMID- 27609444
TI - Recurrent Olfactory Neuroblastoma in Remote Leptomeninges, Mimicking Intracranial
Meningioma.
AB - BACKGROUND: Olfactory neuroblastoma (ONB) is an uncommon neoplasm that arises
from olfactory epithelium in the nasal cavity near the cribriform plate. Although
local recurrence or direct extension along olfactory epithelium and metastasis to
the central nervous system has been reported, remote leptomeningeal metastasis is
quite rare. In our report of a leptomeningeal metastasis of ONB without
recurrence of primary site, we discuss the possible pathogenesis of this rare
phenomenon with a review of the literature. CASE DESCRIPTION: A 56-year-old woman
was admitted with epistaxis. Magnetic resonance imaging revealed a mass in the
right cribriform plate and ethmoid sinus with intracranial extension. She was
primarily treated with craniofacial resection followed by radiotherapy. Gross
total resection was achieved, but annual follow-up magnetic resonance imaging
showed a new enhancing mass in the left parietal meninges mimicking meningioma
without local recurrence at 5 years after the first operation. A second operation
was performed, and pathologic examination confirmed the lesion as metastatic
olfactory neuroblastoma. CONCLUSIONS: ONB is a locally aggressive tumor, but it
also potentially spreads to remote leptomeninges via blood or cerebrospinal
fluid. Therefore, careful evaluation is needed not to misdiagnose a meningioma
and delay the treatment. Moreover, understanding the route of remote
leptomeningeal metastasis and en-bloc resection of tumor at first operation might
reduce leptomeningeal metastasis, irrespective of surgical corridors.
PMID- 27609446
TI - Morgagni Spine Fractures-Dislocations per Anatomen Indagatis: Since the Dawn of
Modern Medicine A Taxonomy and Pathomorphology Problem.
AB - The aim of this study is to retrieve and bring back to light a part of the
astonishing and painstaking work of the legendary Italian father of modern
pathology Giovanni Battista Morgagni, concerning one of most discussed topics in
spine surgery: spine fractures-dislocations. All the excerpts selected for this
study are contained in De sedibus et causis morborum per anatomen indagatis, the
summa maxima of the entire production of Morgagni. This treatise encloses the
enormous experience of Morgagni in anatomic dissections and pathologic
investigations. With the aid of a strict dissection and description methodology,
Morgagni identified and described many of the most important aspects of spinal
fractures-dislocations, from the importance of the mechanism of injury, to the
relevance of ligamentous complex, or the risk of posttraumatic kyphosis and the
clinical expression of spinal cord injury.
PMID- 27609448
TI - Lumbosacral Epidural Lipomatosis: A Retrospective Matched Case-Control Database
Study.
AB - OBJECTIVE: We present the largest known consecutive series of patients with
epidural lipomatosis (EL) to characterize demographics and clinical symptoms of
patients with EL on magnetic resonance imaging (MRI), and compare these
characteristics against a matched control group. METHODS: Patients evaluated for
pathology requiring lumbar MRI imaging between September 2010 and September 2015
were retrospectively reviewed and included in this study if they were diagnosed
with EL on a radiologic note during any visit to our medical center. One hundred
ninety-nine patients fulfilled the study criteria and were included in the study
cohort. A separate patient cohort of 199 unique, age- and gender-matched controls
without lumbosacral EL was generated from a database of patients with lumbar MRI
imaging during the same period. RESULTS: Average age at diagnosis was 54.9 years
(range, 25-84 years). One hundred thirty-three patients (66.8%) were men. On
univariate analysis, patients with EL were more likely to have history of smoking
(odds ratio [OR] 1.90, 95% confidence interval [CI] 1.23-2.94, P = 0.004),
diabetes mellitus type 2 (OR 2.17, 95% CI 1.33-3.56, P = 0.002), or be on
disability (OR 4.43, 95% CI 2.48-7.91, P < 0.001). Furthermore, patients with EL
had significantly increased median body mass index compared with controls (36.7
vs. 29.4 kg/m2; P < 0.001). CONCLUSIONS: Patients with lumbosacral EL tend to be
obese with a high incidence of type 2 diabetes mellitus, suggesting that this
pathology may be a sequela of metabolic syndrome. Future research topics should
include the pathogenesis of EL, as well as treatment outcomes of surgical versus
primary care management.
PMID- 27609449
TI - Encasement of the Cauda Equina After Early Childhood Meningitis: Case Report and
Review of the Literature.
AB - BACKGROUND: Arachnopathy following meningitis has been described in the setting
of chronic spinal arachnoiditis and more recently as shunt-related progressive
myelopathy due to meningeal thickening. CASE DESCRIPTION: We describe an atypical
case of a patient who presented with chronic arachnopathy 5 decades after an
episode of meningitis. We also review the literature concerning arachnopathies
occurring in the context of early childhood meningitis. Although our case bore
clinical and radiologic similarities to chronic spinal arachnoiditis and shunt
related progressive myelopathy, time to symptom onset, intraoperative findings,
pathophysiology, and surgical outcome set it apart from both conditions.
CONCLUSIONS: It is challenging but worthwhile to recognize this separate entity
because, in contrast to both shunt-related progressive myelopathy due to
meningeal thickening and adhesive arachnoiditis, surgery involving microsurgical
dissection of the thick arachnoid encasement of the cauda equina may be curative
in medically refractory cases.
PMID- 27609447
TI - A Novel Approach Using Electromagnetic Neuronavigation and a Flexible
Neuroendoscope for Placement of Ommaya Reservoirs.
AB - OBJECTIVE: Placement of intraventricular catheters in oncology patients can be
associated with morbidity given their small to slit-like ventricles and
underlying hematologic disorders. We studied the accuracy of placing Ommaya
reservoirs using neuronavigation and a flexible neuroendoscope to verify catheter
positioning. METHODS: Ommaya reservoirs placed in 25 oncology patients between
2013 and 2015 were retrospectively reviewed. Twenty-five ventricular catheters
were placed using the AxiEM stealth frameless neuronavigation system and a
flexible neuroendoscope. Postoperative catheter accuracy, operative
complications, and postoperative complications were assessed. We discuss surgical
protocol and technical nuances. RESULTS: All ventricular catheters were
successfully placed into the ipsilateral (84%) or contralateral (16%) foramen of
Monro. A single ventricular catheter pass was needed to cannulate the ventricle
in 96% of patients. The mean accuracy was 4.09 +/- 3.47 mm from the target, the
ipsilateral foramen of Monro. One patient had a catheter tract hemorrhage seen on
postoperative imaging related to thrombocytopenia. No postoperative neurologic
deficits were seen. CONCLUSIONS: A combined neuronavigation and neuroendoscopic
approach improved catheter tip accuracy compared with accuracy rates described in
the literature using other techniques. This approach can be adapted toward
routine clinical practice of placing ventricular shunt catheters and Ommaya
reservoirs.
PMID- 27609451
TI - Investigating the Role of Ethnicity and Race in Patients Undergoing Treatment for
Intracerebral Aneurysms Between 2008 and 2013 from a National Database.
AB - BACKGROUND: The objective of this study is to classify patients using federally
mandated categories of ethnicity and race and to determine whether subgroups are
associated with patient outcomes and aneurysmal subarachnoid hemorrhage (SAH).
METHODS: The American College of Surgeons National Surgical Quality Improvement
Program database from 2008 to 2013 was used to identify patients undergoing
treatment of an intracerebral aneurysm. Ethnicity and race were combined to
create subgroups. A descriptive statistical analysis was performed and a
multivariable logistic regression model was tested whether ethnic and racial
subgroups were associated with SAH. RESULTS: A total of 686 patients met the
study criteria. There were no endovascular cases reported. Four subgroups were
identified, which included non-Hispanic Whites (n = 504, 73.47%, NH Whites),
Hispanic Whites (n = 38, 5.54%), non-Hispanic Blacks (n = 109, 15.89%, NH
Blacks), and non-Hispanic Asians (n = 35, 5.10%, NH Asians). Significant
statistical associations were found between subgroups and the following baseline
variables: age, female gender, body mass index, smoking, and treated hypertension
(all P < 0.01). The NH Whites had the lowest proportion of SAH diagnosis
(30.91%), which was statistically significant (P < 0.001). Multivariable logistic
regression model adjusted for age, smoking, female gender, hypertension, and
multiple comparisons found a statistically significant difference only between NH
Asians compared with NH Whites (odds ratio = 1.25, 95% confidence interval 0.25
2.29, P < 0.01). Postoperative outcomes were similar across ethnic and racial
subgroups. CONCLUSIONS: There are differences in baseline characteristics and the
proportion of SAH. Future studies must take into account risk factors and
outcomes not reported in the database.
PMID- 27609450
TI - Aneurysm Surgery with Preoperative Three-Dimensional Planning in a Virtual
Reality Environment: Technique and Outcome Analysis.
AB - OBJECTIVE: Aneurysm surgery demands precise spatial understanding of the vascular
anatomy and its surroundings. We report on a decade of experience planning
clipping procedures preoperatively in a virtual reality (VR) workstation and
present outcomes with respect to mortality, morbidity, and aneurysm occlusion
rate. METHODS: Between 2006 and 2015, the clipping of 115 intracranial aneurysms
in 105 patients was preoperatively planned with the Dextroscope, a stereoscopic,
patient-specific VR environment. The outcome data for all cases, planned and
performed in 3 institutions, were analyzed based on clinical charts and
radiologic reports. RESULTS: Eighty-five incidental, unruptured aneurysms in 77
patients were electively planned and treated surgically. Mortality was 0% and
morbidity (modified Rankin Scale score >2) was 2.6%. The rate of complete
aneurysm obliteration on postoperative imaging was 91.8%. In addition, 30
aneurysms were treated in 28 patients with previous subarachnoid hemorrhage.
Mortality in these cases was 3.6%, morbidity (modified Rankin Scale score >2)
7.1%, and the rate of complete aneurysm clipping was 90%. CONCLUSIONS: Meticulous
three-dimensional surgical planning in a VR environment enhances the surgeon's
spatial understanding of the individual vascular anatomy and allows clip
preselection and positioning as well as anticipation of potential difficulties
and complications. VR planning was associated, in this multi-institutional
series, with excellent clinical outcomes and rates of complete aneurysm closure
equivalent to benchmark cohorts.
PMID- 27609452
TI - Bilateral Subaxial Rotational Vertebral Artery Occlusion in a Setting of a Prior
Cervical Construct.
AB - BACKGROUND: Rotational vertebral artery occlusion, or bow hunter's syndrome, most
commonly affects the C1-2 level because of its importance in regulating
rotational movement. CASE DESCRIPTION: A 50-year-old man with increasing neck
pain and severe symptoms of vertebrobasilar insufficiency with bidirectional head
rotation had undergone several prior subaxial cervical spine operations. Dynamic
cerebral angiography demonstrated complete occlusion of the left vertebral artery
during head rotation to the right and complete occlusion of the right vertebral
artery during head rotation to the left. Occlusions occurred at the level of and
rostral to his prior construct, with immediate recurrence of debilitating vertigo
and near syncope. Successful radiographic and clinical resolution of symptoms was
achieved by posterior instrumentation and fusion from C2, connecting to his prior
hardware. CONCLUSIONS: A brief literature review and treatment options are
discussed for this unusual presentation of a rare clinical entity.
PMID- 27609453
TI - Scalp Tissue Expansion Above a Custom-Made Hydroxyapatite Cranial Implant to
Correct Sequelar Alopecia on a Transposition Flap.
AB - BACKGROUND: Resection of cranial tumors involving both bone and scalp tissue may
require the recruitment of soft tissue using a flap above the bone
reconstruction. When a transposition flap has been chosen, the alopecia zone on
the donor site may be difficult to treat afterward. Scalp expansion is the gold
standard in these situations, but this has never been described above cranial
implants. We report the first case of a patient who underwent a scalp tissue
expansion above a custom-made hydroxyapatite cranial implant to correct sequelar
alopecia. CASE DESCRIPTION: A 30-year-old man presented with a
dermatofibrosarcoma of the scalp with bone invasion. A cranioplasty with a custom
made hydroxyapatite implant and a transposition flap were performed. Although
healing was achieved, the donor site of the transposition flap left a 9 * 13 cm
sequelar alopecia area on the vertex. To correct it, a rectangular 340-cm3
expander was partially placed above the cranial implant and under the
transposition flap. A second 120-cm3 expander was put on the contralateral
temporal region. The expansion was successful. No expander infection, cranial
implant displacement, or fracture on imaging performed during the follow-up
period was detected. The alopecia zone was entirely excised. The patient was very
satisfied with the cosmetic result. CONCLUSIONS: Tissue expansion above
hydroxyapatite implants may be of concern to the physician because of the risk of
infection and rupture of the cranial implant. With this clinical case, we
emphasize some precautions to prevent these issues.
PMID- 27609455
TI - Reading and lexicalization in opaque and transparent orthographies: Word naming
and word learning in English and Spanish.
AB - Do skilled readers of opaque and transparent orthographies make differential use
of lexical and sublexical processes when converting words from print to sound?
Two experiments are reported, which address that question, using effects of
letter length on naming latencies as an index of the involvement of sublexical
letter-sound conversion. Adult native speakers of English (Experiment 1) and
Spanish (Experiment 2) read aloud four- and seven-letter high-frequency words,
low-frequency words, and nonwords in their native language. The stimuli were
interleaved and presented 10 times in a first testing session and 10 more times
in a second session 28 days later. Effects of lexicality were observed in both
languages, indicating the deployment of lexical representations in word naming.
Naming latencies to both words and nonwords reduced across repetitions on Day 1,
with those savings being retained to Day 28. Length effects were, however,
greater for Spanish than English word naming. Reaction times to long and short
nonwords converged with repeated presentations in both languages, but less in
Spanish than in English. The results support the hypothesis that reading in
opaque orthographies favours the rapid creation and use of lexical
representations, while reading in transparent orthographies makes more use of a
combination of lexical and sublexical processing.
PMID- 27609454
TI - Maternal expression and early induction of histone gene transcription factor
Hinfp sustains development in pre-implantation embryos.
AB - Fidelity of histone gene expression is important for normal cell growth and
differentiation that is stringently controlled during development but is
compromised during tumorigenesis. Efficient production of histones for packaging
newly replicated DNA is particularly important for proper cell division and
epigenetic control during the initial pre-implantation stages of embryonic
development. Here, we addressed the unresolved question of when the machinery for
histone gene transcription is activated in the developing zygote to accommodate
temporal demands for histone gene expression. We examined induction of Histone
Nuclear Factor P (HINFP), the only known transcription factor required for
histone H4 gene expression, that binds directly to a unique H4 promoter-specific
element to regulate histone H4 transcription. We show that Hinfp gene transcripts
are stored in oocytes and maternally transmitted to the zygote. Transcripts from
the paternal Hinfp gene, which reflect induction of zygotic gene expression, are
apparent at the 4- to 8-cell stage, when most maternal mRNA pools are depleted.
Loss of Hinfp expression due to gene ablation reduces cell numbers in E3.5 stage
embryos and compromises implantation. Reduced cell proliferation is attributable
to severe reduction in histone mRNA levels accompanied by reduced cell survival
and genomic damage as measured by cleaved Caspase 3 and phospho-H2AX staining,
respectively. We conclude that transmission of maternal Hinfp transcripts and
zygotic activation of the Hinfp gene together are necessary to control H4 gene
expression in early pre-implantation embryos in order to support normal embryonic
development.
PMID- 27609456
TI - Effect of human papillomavirus seropositivity and E2F2 promoter variants on risk
of squamous cell carcinomas of oropharynx and oral cavity.
AB - Given roles of HPV and genetic factors in cancer risk, we evaluated associations
of HPV16 seropositivity and five E2F2 promoter variants with squamous cell
carcinoma of oropharynx (SCCOP) and squamous cell carcinoma of oral cavity
(SCCOC) risk in a case-control study of 325 patients and 335 cancer-free matched
controls. We found that HPV16 seropositivity was significantly associated with
SCCOP risk (aOR, 5.4, 95%CI, 3.7-8.9) but not SCCOC (aOR, 0.8, 95%CI, 0.4-1.5),
while each E2F2 polymorphism had no significant main effect on SCCOP and SCCOC
risk. However, after combining HPV serological status and E2F2 promoter variants
together, the modification effect of HPV serology and individual or combined risk
genotypes of five polymorphisms on risk was significantly higher among SCCOP than
among SCCOC. Furthermore, the stratified analysis by smoking status showed that
all such modifying effects aforementioned on SCCOP were more pronounced in never
smokers than in smokers. These findings are in agreement with those of previous
studies, in which a majority of SCCOP were caused by HPV infection, whereas most
SCCOC were found to be caused by smoking and drinking. Taken together, these
findings indicate that the risk of SCCOP as opposed to SCCOC associated with
HPV16 seropositivity was modified by E2F2 promoter variants either individually
or jointly, especially in never smokers.
PMID- 27609458
TI - A questionnaire survey on diseases and problems affecting sheep and goats in
communal farming regions of the Eastern Cape province, South Africa.
AB - A questionnaire of 15 questions was completed by four categories of respondents
with the aim of establishing the experience and opinions of these groups on the
constraints including animal health problems for communal, small-scale sheep and
goat farming in the Eastern Cape province of South Africa. The questionnaires
were completed independently and categories were representative of the areas
investigated. Analysis of responses was done by means, ranges, votes and clusters
of responses. Comparisons between the responses of the four categories were made
to identify similarities or contrasts. The results revealed that of non
veterinary concerns, stock theft was the major problem for these farms. Nutrition
was a further major constraint. A third area of significant concern was the
provision or availability of facilities like fences, water troughs, dips and
sheds. Lack of marketing and business skills were also seen as important
deficiencies to be rectified so as to promote profitable farming. Of the most
important veterinary problems identified, the provision, availability, cost and
care of drugs and vaccines were seen as major stumbling blocks to effective
disease control, as well as lack of access to veterinary services. The most
important diseases that constrain small-ruminant livestock farming in the farming
systems investigated were sheep scab and other ectoparasites, heart water,
enterotoxaemia, internal parasites and bluetongue. A lack of knowledge in key
areas of small-stock farming was revealed and should be rectified by an effective
training and support programme to improve the contribution of small-ruminant
farming to livelihoods in these communities.
PMID- 27609457
TI - Honokiol suppresses pancreatic tumor growth, metastasis and desmoplasia by
interfering with tumor-stromal cross-talk.
AB - The poor clinical outcome of pancreatic cancer (PC) is largely attributed to its
aggressive nature and refractoriness to currently available therapeutic
modalities. We previously reported antitumor efficacy of honokiol (HNK), a
phytochemical isolated from various parts of Magnolia plant, against PC cells in
short-term in vitro growth assays. Here, we report that HNK reduces plating
efficiency and anchorage-independent growth of PC cells and suppresses their
migration and invasiveness. Furthermore, significant inhibition of pancreatic
tumor growth by HNK is observed in orthotopic mouse model along with complete
blockage of distant metastases. Histological examination suggests reduced
desmoplasia in tumors from HNK-treated mice, later confirmed by
immunohistochemical analyses of myofibroblast and extracellular matrix marker
proteins (alpha-SMA and collagen I, respectively). At the molecular level, HNK
treatment leads to decreased expression of sonic hedgehog (SHH) and CXCR4, two
established mediators of bidirectional tumor-stromal cross-talk, both in vitro
and in vivo . We also show that the conditioned media (CM) from HNK-treated PC
cells have little growth-inducing effect on pancreatic stellate cells (PSCs) that
could be regained by the addition of exogenous recombinant SHH. Moreover,
pretreatment of CM of vehicle-treated PC cells with SHH-neutralizing antibody
abolishes their growth-inducing potential on PSCs. Likewise, HNK-treated PC cells
respond poorly to CM from PSCs due to decreased CXCR4 expression. Lastly, we show
that the transfection of PC cells with constitutively active IKKbeta mutant
reverses the suppressive effect of HNK on nuclear factor-kappaB activation and
partially restores CXCR4 and SHH expression. Taken together, these findings
suggest that HNK interferes with tumor-stromal cross-talk via downregulation of
CXCR4 and SHH and decreases pancreatic tumor growth and metastasis.
PMID- 27609459
TI - A radiological evaluation of alveolar bone regeneration between the left and
right mandibles and maxillae of the Chacma baboon.
AB - There is a lack of information in comparing the healing rate between the left and
right sides of the maxilla and mandible. Osteogenesis of alveolar bone was
evaluated with digital radiology by comparing differences in bone density (BD) at
different time points within the left and right maxilla and mandible. Alveolar
bone defects were created in five healthy Chacma baboons. Standardised x-ray
images were acquired over time and the densities of the selected trauma areas
were measured pre-operatively, post-operatively and at 3 and 6 weeks post
operatively. Differences in densities were statistically tested. There was no
significant difference when the grey scale averages of the combined first and
fourth quadrants (right side) and combined second and third quadrants (left side)
were compared pre-operatively (t = 0.70), immediately post-operatively (t =
0.34), 3 weeks post-operatively (t = 0.40) and 6 weeks post-operatively (t =
0.66). There was also no significant difference between the values for the first
and second quadrants (maxilla) pre-operatively (t = 0.37), immediately post
operatively (t = 0.30), 3 weeks post-operatively (t = 0.30) and 6 weeks post
operatively (t = 0.38); the third and fourth quadrants (mandible) were also not
significantly different pre-operatively (t = 0.29), immediately post-operatively
(t = 0.69), 3 weeks post-operatively (t = 0.07) and 6 weeks postoperatively (t =
0.06). However, the results showed an increased predisposition of the right side
to regenerate faster than the left side and indicated sufficient information to
investigate the effect of laterality and preferred side of mastication on the
rate of healing and alveolar BD in the maxilla and mandible.
PMID- 27609460
TI - Women's opinions of legal requirements for drug testing in prenatal care.
AB - PURPOSE: To explore women's attitudes and perceptions regarding legal
requirements for prenatal drug testing. METHODS: Web-based survey of 500 US women
(age 18-45) recruited from a market research survey panel. A 24-item
questionnaire assessed their opinion of laws requiring doctors to routinely
verbal screen and urine drug test patients during pregnancy; recommendations for
consequences for positive drug tests during pregnancy; and opinion of laws
requiring routine drug testing of newborns. Additional questions asked
participants about the influence of such laws on their own care-seeking
behaviors. Data were analyzed for associations between participant
characteristics and survey responses using Pearson's chi-squared test. RESULTS:
The majority of respondents (86%) stated they would support a law requiring
verbal screening of all pregnant patients and 73% would support a law requiring
universal urine drug testing in pregnancy. Fewer respondents were willing to
support laws that required verbal screening or urine drug testing (68% and 61%,
respectively) targeting only Medicaid recipients. Twenty-one percent of
respondents indicated they would be offended if their doctors asked them about
drug use and 14% indicated that mandatory drug testing would discourage prenatal
care attendance. CONCLUSION: Women would be more supportive of policies requiring
universal rather than targeted screening and testing for prenatal drug use.
However, a noteworthy proportion of women would be discouraged from attending
prenatal care - a reminder that drug testing policies may have detrimental
effects on maternal child health.
PMID- 27609462
TI - Response of Salmonella Typhi to bile-generated oxidative stress: implication of
quorum sensing and persister cell populations.
AB - Salmonella Typhi can chronically persist within the gallbladder of patients
suffering from gallbladder diseases. This study, intended to improve our
understanding of bacterial mechanisms underlying bile adaptation, revealed that
bile, which is a bactericidal agent, led to the generation of reactive oxygen
species in S Typhi. Salmonella Typhi in response showed a significant increase in
the production of anti-oxidative enzymes, namely superoxide dismutase and
catalase. The work reports that the quorum-sensing (QS) system of S Typhi
regulates the level of these enzymes during oxidative stress. In support of these
observations, the quorum-sensing mutant of S Typhi was found to be sensitive to
bile with significantly lower levels of anti-oxidant enzymes compared to other
clinical isolates. Furthermore the addition of exogenous cell-free extracts
(CFEs) of S Typhi containing the quorum-sensing signalling molecule significantly
increased the levels of these enzymes within the mutant. Interestingly the CFE
addition did not significantly restore the biofilm-forming ability of the mutant
strain when compared with the wild-type. In the presence of ciprofloxacin and
ampicillin, S Typhi formed persister cells which increased >3-fold in the
presence of bile. Thus the QS-system of S Typhi aids in oxidative stress
management, and enhanced persister cell populations could assist chronic
bacterial persistence within the gallbladder.
PMID- 27609463
TI - The mimic epitopes of Mycobacterium tuberculosis screened by phage display
peptide library have serodiagnostic potential for tuberculosis.
AB - Mycobacterium tuberculosis is an obligate pathogenic bacterial species in the
family of Mycobacteriaceae and attracts excessive immune responses which cause
pathology of the lungs in active tuberculosis. The lack of more sensitive and
effective diagnosis reagents advocates a further recognition for the fast
diagnostic and immunological measures for tuberculosis. Here, two 12-mer peptides
with core sequences of SVSVGMKPSPRP (CS1) and TMGFTAPRFPHY (CS2) were screened
from a phage display random peptide library using the purified mixed tuberculosis
positive serum as a target. Enzyme-linked immunosorbent assay (ELISA) and dot
immunobinding assay verified that positive phages exhibited strong binding
affinity to mixed tuberculosis-positive serum. BLAST analysis showed that the two
sequences may be mimotopes of the Mycobacterium tuberculosis The diagnostic
potential for two synthetic mimotope peptides CS1 and CS2 was evaluated using
different panels of serum samples (n = 181) by ELISA, and the diagnostic
parameters were calculated. CS1 and CS2 achieved sensitivity of 89.41% and
85.88%, and specificities were 90.63% and 87.50%, respectively. We hypothesized
that the diagnostic based on CS1 and CS2 may become a promising strategy to
enhance the detection of Mycobacterium tuberculosis infection due to higher
specificity and sensitivity. Therefore, CS1 and CS2 may possess potentials to
provide an experimental basis for the diagnosis of tuberculosis.
PMID- 27609461
TI - Pertussis leukocytosis: mechanisms, clinical relevance and treatment.
AB - The significant and sometimes dramatic rise in the number of circulating white
blood cells (leukocytosis) in infants suffering from pertussis (whooping cough)
has been recognized for over a century. Although pertussis is a disease that
afflicts people of all ages, it can be particularly severe in young infants, and
these are the individuals in whom leukocytosis is most pronounced. Very high
levels of leukocytosis are associated with poor outcome in infants hospitalized
with pertussis and modern treatments are often aimed at reducing the number of
leukocytes. Pertussis leukocytosis is caused by pertussis toxin, a soluble
protein toxin released by Bordetella pertussis during infection, but the exact
mechanisms by which this occurs are still unclear. In this minireview, I discuss
the history of clinical and experimental findings on pertussis leukocytosis,
possible contributing mechanisms causing this condition and treatments aimed at
reducing leukocytosis in hospitalized infants. Since recent studies have detailed
significant associations between specific levels of pertussis leukocytosis and
fatal outcome, this is a timely review that may stimulate new thinking on how to
understand and combat this problem.
PMID- 27609465
TI - Upregulation of CYP2S1 by oxaliplatin is associated with p53 status in colorectal
cancer cell lines.
AB - Oxaliplatin displays a wide spectrum of antitumor activities and is widely used
in the treatment of metastatic colorectal cancer (CRC). However, tumor responses
to this agent are variable, and the underlying mechanisms are poorly understood.
In the present study, oxaliplatin was found to strongly inhibit the growth of
HCT116 cells harboring wild-type p53 but to only weakly inhibit SW480 cells, HT29
cells or p53-/- HCT116 cells, which all lack p53 expression. Administration of
oxaliplatin significantly induced p53 accumulation and enhanced expression of
CYP2S1 in HCT116 cells with wild-type p53. CYP2S1 knockdown conferred a cell
survival advantage after oxaliplatin treatment to cells harboring wild-type p53
in vitro and in vivo. Interestingly, enzyme immunoassays, TOPFlash/FOPFlash
reporter activity assays and western blotting analysis demonstrated oxaliplatin
mediated downregulation of PGE2 and Wnt/beta-catenin signaling in a manner
dependent on p53. Moreover, oxaliplatin treatment of mice with subcutaneous tumor
xenografts drastically reduced the volume of wild-type p53 HCT116 tumors but had
no effect on isogenic p53-/- HCT116 tumors. These results suggest that
oxaliplatin exerts its inhibitory effects in human CRC cells via upregulation of
CYP2S1 expression in a p53-dependent manner.
PMID- 27609467
TI - How does the supernatant of Lactobacillus acidophilus affect the proliferation
and differentiation activities of rat bone marrow-derived stromal cells?
AB - Low proliferation rate and unwanted differentiation of bone marrow-derived
stromal cells (rBMSCs) during the frequent passages have limited the use of such
cells in clinical cell therapy. Recently, the researchers have focused on the
effects of the components produced by some bacteria on proliferation of the stem
cells. In this study, we discussed the possible effects of the Lactobacillus
acidophilus supernatant on proliferation and differentiation of the rBMSCs. For
this aim, the cells were isolated from rat bone marrow, characterized by
culturing on tissue specific differentiation media and stained. The cells
(passage two) were treated with different concentrations of the L. acidophilus
supernatant (0, 0.1, 0.3, 0.9, 3, 9 and 30 &mgr;l/ml) for 14 days. The
proliferation and differentiation capacity of the cells were then determined by 3
(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT assay) and tissue
specific staining. The results showed a positive effect of the supernatant on the
cell proliferation in 3 and 9 &mgr;l/ml concentrations, while did not affect the
differentiation capacity of the rBMSCs. The current study strongly suggests the
L. acidophilus supernatant as an alternative material that could be added to the
media with aim of improvement in the proliferation rate of the rBMSCs without
affecting their differentiation capacity.
PMID- 27609466
TI - Assessment of Hg Pollution Released from a WWII Submarine Wreck (U-864) by Hg
Isotopic Analysis of Sediments and Cancer pagurus Tissues.
AB - Hg pollution released from the U-864 submarine sunk during WWII and potential
introduction of that Hg into the marine food chain have been studied by a
combination of quantitative Hg and MeHg determination and Hg isotopic analysis
via cold vapor generation multicollector inductively coupled plasma-mass
spectrometry (CVG-MC-ICP-MS) in sediment and Cancer pagurus samples. The sediment
pollution could be unequivocally linked with the metallic Hg present in the
wreck. Crabs were collected at the wreck location and 4 nmi north and south, and
their brown and claw meat were analyzed separately. For brown meat, the
delta202Hg values of the individuals from the wreck location were shifted toward
the isotopic signature of the sediment and, thus, the submarine Hg. Such
differences were not found for claw meat. The isotope ratio results suggest
direct ingestion of metallic Hg by C. pagurus but do not offer any proof for any
other introduction of the submarine Hg into the marine food chain.
PMID- 27609464
TI - Loss of mesenchymal bone morphogenetic protein signaling leads to development of
reactive stroma and initiation of the gastric neoplastic cascade.
AB - Bmps are morphogens involved in various gastric cellular functions. Studies in
genetically-modified mice have shown that Bmp disruption in gastric epithelial
and stromal cell compartments leads to the development of tumorigenesis. Our
studies have demonstrated that abrogation of gastric epithelial Bmp signaling
alone was not sufficient to recapitulate the neoplastic features associated with
total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not
appear to be a key player in gastric tumorigenesis initiation. These observations
suggest a greater role for stromal Bmp signaling in gastric polyposis initiation.
In order to identify the specific roles played by mesenchymal Bmp signaling in
gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling
exclusively in the gastro-intestinal mesenchyme (Bmpr1a(DeltaMES)). We were able
to expose an unsuspected role for Bmp loss of signaling in leading normal gastric
mesenchyme to adapt into reactive mesenchyme. An increase in the population of
activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed
in mutant stomach. Bmpr1a(DeltaMES) stomachs exhibited spontaneous benign polyps
with presence of both intestinal metaplasia and spasmolytic-polypeptide
expressing metaplasia as early as 90 days postnatal. These results support the
novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in
gastric polyposis initiation.
PMID- 27609468
TI - Genetic basis of resistance waves among methicillin resistant Staphylococcus
aureus isolates recovered from milk and meat products in Egypt.
AB - Antimicrobial resistance of methicillin-resistant Staphylococcus aureus (MRSA)
poses a serious problem for clinicians worldwide. The present study attempted to
evaluate the susceptibility patterns of MRSA to various antimicrobials and the
prevalence of inducible clindamycin resistance as well as the relevant antibiotic
and antiseptic resistance genes among these isolates. Totally, 40 MRSA isolates
were recovered from examined milk and meat product samples (18.60%). Multi-drug
resistance (MDR) was remarkably observed among 85% of these isolates. There was a
good correlation between phenotypic determination of methicillin,
amoxicillin/clavulinic acid and tetracycline resistances and PCR detections of
mecA, blaZ and tet(K) genes, respectively, but norA gene was not detected in the
four ciprofloxacin resistant isolates. Although, 55% of MRSA expressed resistance
to benzalkonium chloride (BC), neither qacA/B nor smr gene was detected. Of 20
isolates exhibiting erythromycin- clindamycin discordant resistance pattern, 8
displayed positive double disk diffusion (D-zone) test denoting inducible
macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype with the
inducibly expressed erm(A) and erm(C) genes in 87.5% of these isolates. Besides,
the remaining 12 isolates showed MS phenotype (resistant to macrolides and type B
streptogramins only) with a variety of erm(A), mph(C), msr(A) or a combination of
these genes including erm(C). Finally, the constitutive MLSB phenotype with the
constitutive expression of erm(A), erm(B) and erm(C) genes was comprised in 2
isolates with higher minimum inhibitory concentration (MIC) values for
erythromycin (512 and 1024 ug/ml) and clindamycin (16 and 32 ug/ml). These
findings suggested the importance of monitoring the evolution of MRSA resistance.
PMID- 27609469
TI - Modifying the mechanical properties of silk nanofiber scaffold by knitted
orientation for regenerative medicine applications.
AB - Tissue reconstruction is among the increasing applications of polymer nanofibers.
Fibrous scaffolds (mats) can be easily produced using the electrospinning method
with structure and biomechanical properties similar to those of a cellular
matrix. Electrospinning is widely used in the production of nanofibers and the
GAP-method electrospinning is one of the means of producing fully aligned
nanofibers. In this research, using the GAP-method, knitted fibrous scaffolds
were made of silk fibroin, which is a biocompatible and biodegradable polymer. To
extract fibroin from cocoons, the sodium chloride solution as well as dialysis
and freeze-drying techniques were employed. The molecular weight of the extracted
fibroin was measured with the SDS-Page electrophoresis technique. Moreover, the
pure fibroin structure was examined using the ATR-FTIR method, and the viscosity
of the solution used for electrospinning was measured with the Brookfield
rotational viscometer. The scaffolds were prepared through electrospinning of the
silk fibroin in pure formic acid solution. The following three structures were
electrospun: 1) a random structure; 2) a knitted structure with an interstitial
angle of 60 degrees; 3) a knitted structure with an interstitial angle of 90
degrees. Morphology of the resulting fibers was studied with a SEM (scanning
electron microscope). Fibroin scaffolds are degradable in water. Therefore, they
were fixated through immersion in methanol to be prepared for assays. The
mechanical properties of the scaffolds were also studied using a tensile strength
test device. The effect of methanol on the strength properties of the samples was
also assessed. The hydrophilic potential of the samples was measured via a
contact angle test. To increase the hydrophilicity of the scaffold surfaces, the
cold oxygen plasma technique was employed. Finally, the biocompatibility and cell
adhesion of the resulting scaffolds were examined through a HEK 293 cell culture,
and the results were analyzed through the MTT, DAPI staining, and SEM imaging
techniques. Results revealed that the oriented knitted structure contributed to
the increase in Young's modulus and the maximum strength of scaffolds as
compared to the random samples. Moreover, this structure can also be a suitable
alternative to the typical chemical means of increasing strength.
PMID- 27609470
TI - RNAi-induced silencing in floral tissues of Petunia hybrida by agroinfiltration:
a rapid assay for chalcone isomerase gene function analysis.
AB - Variegation in flower color is commonly observed in many plant species and also
occurs on Petunia (Petunia hybrida) as an ornamental plant. Variegated plants are
of highly valuable in the floricultural market. Agroinfiltration is an
Agrobacterium-mediated transient assay for the analysis of gene function and
genetic modification in leaves, flowers and fruit tissues of various plants.
Transient RNAi-induced silencing by agroinfiltration has been developed in leaves
and fruits of several plant species. Here we report the establishment of a
transient hairpin RNAi-induced silencing system for color modification assay in
floral tissues of Petunia with different colors. chiRNAi construct was cloned
into the pBI121 vector under the control of 35S promoter. Transient RNA silencing
of chi in the floral tissues of Petunia was induced by delivering 530 bp chi
hairpin RNAs (hpRNAs) into the petals of flowers using agroinfiltration. Impaired
anthocyanin accumulation and reduction of endogenous mRNAs of the corresponding
targets were observed in the infiltrated areas of the petals of four colors of
Petunia. Silencing of the endogenous chi mRNAs was highly effective in reduction
of chi gene and anthocyanin accumulation. This transient silencing system is a
prototype for modification of the anthocyanin biosynthetic pathway in Petunia
through chi gene suppression.
PMID- 27609471
TI - Development of a loop-mediated isothermal amplification assay for rapid detection
of Burkholderia mallei.
AB - The present study was conducted to establish a Loop-mediated isothermal
amplification (LAMP) technique for the rapid detection of B. mallei the etiologic
agent of glanders, a highly contagious disease of equines. A set of six specific
primers targeting integrase gene cluster were designed for the LAMP test. The
reaction was optimized using different temperatures and time intervals. The
specificity of the assay was evaluated using DNA from B.pseudomallei and
Pseudomonas aeruginosa. The LAMP products were analyzed both visually and under
UV light after electrophoresis. The optimized conditions were found to be at 63oC
for 60 min. The assay showed high specificity and sensitivity. It was concluded
that the established LAMP assay is a rapid, sensitive and practical tool for
detection of B. mallei and early diagnosis of glanders.
PMID- 27609472
TI - Endophilin B1 regulates EGFR endocytic degradation in prostate cancer cell.
AB - Prostate cancer (Pca) is one of the most common types of cancer for elder men.
Aberrant expression of epidermal growth factor receptor (EGFR) and EGFR
downstream signaling have been known to contribute to disease progression in
prostate cancer. EGF-stimulated EGFR is internalized and the process of endocytic
degradation of EGFR mediates its signaling which is frequently dysregulated in
many kinds of cancer. In the present study, we demonstrated that endophilin B1
expression was inhibited and EGFR expression was significantly increased in
prostate cancer cell lines. We demonstrated that suppression of endophilin B1
increased EGFR levels via delaying EGFR internalization triggered by EGF and its
intracellular degradation. Endophilin B1 decreased also sustained EGFR downstream
signaling such as Erk1/2 phosphorylation in response to EGF stimulation and
promoted prostate cancer cell proliferation which is EGF independent. Our data
indicated that endophilin B1 mediated the biological function of EGFR in cancer
cell proliferation through regulating the EGFR endocytic trafficking and
downstream signaling.
PMID- 27609473
TI - ERBB4 gene polymorphisms and the risk of prostate cancer in a sample of Iranian
Population.
AB - Genetic polymorphisms in ERBB4 are thought to be associated with cancer
susceptibility. In the present study, we aimed to assess the impact of ERBB4
rs12052398 T>C, rs13393577 A>G, rs13424871 A>T, rs16847082 A>G and rs6147150 (12
bp I/D) polymorphisms on risk of prostate cancer (PCa) in a sample of Iranian
population. In a case-control study, we enrolled 169 patients with pathologically
confirmed PCa and 182 subjects with benign prostatic hyperplasia (BPH). No
significant association was found among ERBB4 polymorphisms and risk of PCa.
Subjects carrying TT/AA/AA/AG/ID, TC/AA/AA/AA/II, TT/AA/AT/AA/II and
TT/AA/AT/AG/ID genotypes are associated with a decreased risk of PCa. Our
findings suggest that haplotypes CAAAI and TAAAD (rs12052398, rs13393577,
rs13424871, rs16847082 and rs6147150I) of the ERBB4 polymorphisms are associated
with a significantly lower risk of PCa. Further studies with a larger sample
sizes and diverse ethnicities are necessary to verify our findings.
PMID- 27609474
TI - Protective potency of clove oil and its transcriptional down-regulation of
Aeromonas sobria virulence genes in African catfish (Clarias gariepinus L.).
AB - Disease episodes of fish caused by Aeromonas species are moved to the top list of
limiting problems worldwide. The present study was planned to verify the in vitro
antibacterial activities as well as the in vivo potential values of clove oil and
ciprofloxacin against Aeromonas sobria in African catfish (Clarias gariepinus).
The in vitro phenotypic virulence activities and the successful amplification of
aerolysin and hemolysin genes in the precisely identified A. sobria strain were
predictive for its virulence. In the in vivo assay, virulence of A. sobria strain
was fully demonstrated based on constituent mRNA expression profile of tested
virulence genes and typical septicemia associated with high mortalities of
infected fish. Apparent lower mortality rates were correlated well with both
decrescent bacterial burden and significant down-regulated transcripts of
representative genes in the treated groups with clove oil, followed by
ciprofloxacin as a prophylactic use for 15 days (P < 0.0001); however, the
essential oil apart from ciprofloxacin significantly enhanced different
hematological parameters (P < 0.05). In addition, administration of antibiotic
may be considered as a pronounced stress factor in the fish even when it used in
the prophylactic dose. In conclusion, medicinal plants-derived essential oils
provide a virtually safer alternative to chemotherapeutics on fish, consumers and
ecosystems.
PMID- 27609475
TI - Genetic diversity of multidrug resistant Staphylococcus aureus isolated from
clinical and non clinical samples in Egypt.
AB - In recent years, the increasing incidence of diseases caused by Staphylococcus
aureus (S. aureus) has been noted in the university hospitals of El-Sharkia and
Assuit governorates - Egypt. Therefore, we studied the genetic relatedness of
multidrug resistant S. aureus isolates from different sources in the above
mentioned governorates. One hundred and fifty six S. aureus isolates were divided
into 5 different groups, 1 non clinical isolates from different food products and
4 different clinical isolates of human and animal sources in the 2 different
governorates. Epidemiological characteristics of 156 S. aureus isolates were
determined by phenotypic methods including quantitative antibiogram typing and
biofilm production. Genetic typing of 35 multidrug resistant (MDR) isolates (7
from each group) based on 16S rRNA gene sequence, virulence and antimicrobial
resistance gene profiles was done. The genetic relatedness of the highest
virulent strain from each group was detected based on different single locus
sequence typing and multi-locus sequence typing (MLST). S. aureus strains
isolated from different sources and geographical areas showed high diversity. The
genetic typing revealed different sequence types and different sequences of coa
and spa genes. S. aureus isolates were found highly diverse in Egypt.
PMID- 27609476
TI - Three-dimensional stress In vitro promotes the proliferation and differentiation
of periodontal ligament stem cells implanted by bioactive glass.
AB - To analyze the biological and mechanical microenvironment on the directional
differentiation of periodontal ligament stem cells (PDLSCs) In vitro. PDLSCs were
cultured in three-dimensional stress system In vitro for 1, 2 and 3 weeks.
Methods like immunohistochemistry and flow cytometry were adopted and the
proliferation and differentiation situation of PDLSCs were determined. Bioactive
glass (BAG) of 0%, 10%, 20%, 30% and 40% was implanted into PDLSCs with or
without three-dimensional stress for 3 weeks, respectively. The proliferation and
differentiation situation of PDLSCs were determined. The mRNA levels of Alkaline
phosphatase (ALP), Type I Collagen (COL I), Type II Collagen (COL II), Bone
sialoprotein (BSP), Osteocalcin (OCN) and Osteopontin (OPN) were determined by
semi-quantitative RT-PCR. 30% BAG and three-dimensional stress for 3 weeks
promoted the proliferation and differentiation of PDLSCs mostly. PDLSCs induced
by BAG and 3D force and the control all expressed the mRNA of ALP, COLIand COL
II. The BAG and three-dimensional stress induced PDLSCs also expressed the mRNA
of BSP, OCN and OPN. BAG and three-dimensional stress indicated microenvironment
In vitro can promote the proliferation and differentiation of PDLSCs.
PMID- 27609477
TI - Comparative characteristics of mesenchymal stem cells derived from reamer
irrigator-aspirator, iliac crest bone marrow, and adipose tissue.
AB - Mesenchymal stem cells (MSCs) have been considered promising tools for new
clinical concepts in supporting cellular therapy and regenerative medicine. More
recently, Ream/Irrigator/Aspirator (RIA) was introduced as a source of MSCs. In
this study we compared MSCs derived from three different sources (iliac crest
bone marrow (ICBM), adipose tissue (AT), and (RIA)) regarding the morphology, the
success rate of isolating MSCs, colony frequency, expansion potential, osteogenic
and chondrogenic differentiation capacity. MSCs were isolated from three
different sources and flow cytometric analyses were performed for cell
characterization. Colony-forming unit-fibroblast (CFU-F) assay and population
doubling time (PDT) were evaluated for MSCs derived from three different sources
and differentiation potential of RIA, ICBM-, and AT-MSCs were determined by
staining. Additionally, gene expression profiles for tissue specific markers
corresponding to osteogenesis and chondrogenesis were analyzed using real time
polymerase chain reaction (RT-PCR). Cultured with the appropriate condition,
osteogenic and chondrogenic differentiation could be confirmed in all MSC
preparations. Flow cytometry analysis indicated that RIA- and AT-derived MSCs
have more homogenous populations than ICBM-MSCs. A comparison of the colonogenic
ability in different tissues by CFU-F assay after 10 days showed that more
colonies are formed from RIA-MSCs than from ICBM-MSCs, and AT-MSCs. AT-MSCs, were
dispersed with no obvious colonies. The RIA-MSCs underwent osteogenesis and
chondrogenesis at a faster rate than ICBM and AT-MSCs. Direct comparisons of RIA-
to ICBM- and AT-MSCs have shown the RIA-MSCs have higher differentiation toward
osteoblast and chondrocytes compared to other sources of MSCs. Hence, RIA-MSCs
may be recommended as a more suitable source for treating orthopedic disorders.
PMID- 27609478
TI - Mitosis-specific phosphorylation of PML at T409 regulates spindle checkpoint.
AB - During mitosis, Promyelocytic leukemia nuclear bodies (PML NBs) change
dramatically in morphology and composition, but little is known about function of
PML in mitosis. Here, we show that PML is phosphorylated at T409 (PML p409) in a
mitosis-specific manner. More importantly, PML p409 contributes to maintain the
duration of pro-metaphase and regulates spindle checkpoint. Deficient PML p409
caused a shortening of pro-metaphase and challenged the nocodazole-triggered
mitotic arrest. T409A mutation led to a higher frequency of misaligned
chromosomes on metaphase plate, and subsequently death in late mitosis. In
addition, inhibition of PML p409 repressed growth of tumor cells, suggesting that
PML p409 is a potential target for cancer therapy. Collectively, our study
demonstrated an important phosphorylated site of PML, which contributed to
explore the role of PML in mitosis.
PMID- 27609479
TI - The antiproliferative effect of Origanum majorana on human hepatocarcinoma cell
line: suppression of NF-kappaB.
AB - Hepatocellular carcinoma (HCC) is one of the most common cancer types with a high
prevalence and itis the leading cause of cancer deaths worldwide. This study
aimed to investigate the antiproliferative effect of aqueous and ethanol extracts
of Origanum majorana leaf on human hepatocellular carcinoma (HepG2) cell line
through incubation of various concentrations of origanum majorana extracts with
HepG2 and at different time intervals. The effects of aqueous and ethanol
extracts of O. majorana L. on HepG2 cell viability, nuclear factor kappa B (NF
kB) gene expression were examined. The results of the cell viability assays
showed that aqueous and ethanol extracts exhibited a highly significant
inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction
in viable cell count. The results were confirmed by microscopical examination of
cell morphology. Furthermore, the O. majorana L. extracts suppressed the activity
of NF-kB gene expression of HepG2 cells compared to the control.The conclusions
from this study suggest that marjoram extracts exhibit anti-proliferative effect
against HCC through suppressing the activity of NF-kB gene expression and high
antioxidant activity.
PMID- 27609480
TI - Spirulina exhibits hepatoprotective effects against lead induced oxidative injury
in newborn rats.
AB - Lead is a toxic metal that induces a wide range of biochemical and physiological
effects. The present investigation was designed at evaluating the toxic effects
of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and
potent protective effects of spirulina. Female rats were randomly divided into 4
groups which were given a normal diet (control),a diet enriched with spirulina
(S), lead acetate administered through drinking water (Pb), or a diet enriched
with spirulina and lead contaminated water (S Pb), respectively. The duration of
treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity
was assessed by measuring body and liver weights, blood and stomach lead levels,
hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as
well as lipid peroxidation level and activities of antioxidant enzymes in hepatic
tissues of neonates. Lead intoxication of mothers caused reduction of liver
weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover,
oxidative stress and changes in antioxidant enzyme activities were recorded.
Conversely, supplementation of mothers with spirulina mitigated these effects
induced by lead. These results substantiated the potential hepatoprotective and
antioxidant activity of spirulina.
PMID- 27609481
TI - Commitment to personal values and guilt feelings in dementia caregivers.
AB - BACKGROUND: Caregivers' commitment to personal values is linked to caregivers'
well-being, although the effects of personal values on caregivers' guilt have not
been explored to date. The goal of this study is to analyze the relationship
between caregivers' commitment to personal values and guilt feelings. METHOD:
Participants were 179 dementia family caregivers. Face-to-face interviews were
carried out to describe sociodemographic variables and assess stressors,
caregivers' commitment to personal values and guilt feelings. Commitment to
values was conceptualized as two factors (commitment to own values and commitment
to family values) and 12 specific individual values (e.g. education, family or
caregiving role). Hierarchical regressions were performed controlling for
sociodemographic variables and stressors, and introducing the two commitment
factors (in a first regression) or the commitment to individual/specific values
(in a second regression) as predictors of guilt. RESULTS: In terms of the
commitment to values factors, the analyzed regression model explained 21% of the
variance of guilt feelings. Only the factor commitment to family values
contributed significantly to the model, explaining 7% of variance. With regard to
the regression analyzing the contribution of specific values to caregivers'
guilt, commitment to the caregiving role and with leisure contributed negatively
and significantly to the explanation of caregivers' guilt. Commitment to work
contributed positively to guilt feelings. The full model explained 30% of guilt
feelings variance. The specific values explained 16% of the variance. CONCLUSION:
Our findings suggest that commitment to personal values is a relevant variable to
understand guilt feelings in caregivers.
PMID- 27609482
TI - Early vs late cranioplasty: what is better?
AB - AIM OF THE STUDY: Cranioplasty is the surgical repair of skull defects, which
commonly is performed after traumatic skull injuries due to tumor removal or
decompressive craniectomy. Several studies reported improvement in cognitive
functions following cranioplasty in patients with severe brain damage. The
reasons why exist such clinical improvement is not completely understood,
although the increase in cerebrospinal fluid hydrodynamics with the potential
improvement of local and global cerebral hemodynamics, blood flow, and metabolism
may play a pivotal role. We investigated whether the cranioplasty improved
neurological recovery and the whole array of cognitive functions or just some
specific domains. MATERIALS AND METHODS: A total of 30 consecutive brain-injured
subjects with craniectomy were enrolled and underwent a structured
neuropsychological assessment immediately before the cranioplasty, 1 month after
the cranioplasty and 1 year after the surgical procedure. RESULTS: Our results
showed that cranioplasty may facilitate the cognitive recovery, independently
from the surgical timing. Particularly, we observed an important cognitive
recovery in the period immediately after cranioplasty, while the improvement
trend settles after a lapse of time, and the recovery starts to slow down.
CONCLUSIONS: Cranioplasty seems to significantly improve neuropsychological and
motor status in the patients with skull defects, independently from cranioplasty
timing and patient's clinical status.
PMID- 27609483
TI - Impact of Degree Heterogeneity on Attack Vulnerability of Interdependent
Networks.
AB - The study of interdependent networks has become a new research focus in recent
years. We focus on one fundamental property of interdependent networks:
vulnerability. Previous studies mainly focused on the impact of topological
properties upon interdependent networks under random attacks, the effect of
degree heterogeneity on structural vulnerability of interdependent networks under
intentional attacks, however, is still unexplored. In order to deeply understand
the role of degree distribution and in particular degree heterogeneity, we
construct an interdependent system model which consists of two networks whose
extent of degree heterogeneity can be controlled simultaneously by a tuning
parameter. Meanwhile, a new quantity, which can better measure the performance of
interdependent networks after attack, is proposed. Numerical simulation results
demonstrate that degree heterogeneity can significantly increase the
vulnerability of both single and interdependent networks. Moreover, it is found
that interdependent links between two networks make the entire system much more
fragile to attacks. Enhancing coupling strength between networks can greatly
increase the fragility of both networks against targeted attacks, which is most
evident under the case of max-max assortative coupling. Current results can help
to deepen the understanding of structural complexity of complex real-world
systems.
PMID- 27609484
TI - The Combination of Cyst Fluid Carcinoembryonic Antigen, Cytology and Viscosity
Increases the Diagnostic Accuracy of Mucinous Pancreatic Cysts.
AB - Background/Aims: The objective of this study was to investigate the value of cyst
fluid carcinoembryonic antigen (CEA) in combination with cytology and viscosity
for the differential diagnosis of pancreatic cysts. Methods: We retrospectively
reviewed our data for patients who underwent endoscopic ultrasound-guided fine
needle aspiration (EUS-FNA) and cyst fluid analysis. We investigated the
sensitivity, specificity and accuracy of the combination of cyst fluid CEA,
cytology and viscosity testing. Results: A total of 177 patients underwent EUS
FNA and cyst fluid analysis. Of these, 48 subjects were histologically and
clinically confirmed to have pancreatic cysts and were therefore included in the
analysis. Receiver operator curve analysis demonstrated that the optimal cutoff
value of cyst fluid CEA for differentiating mucinous versus nonmucinous cystic
lesions was 48.6 ng/mL. The accuracy of cyst fluid CEA (39/48, 81.3%) was greater
than the accuracy of cytology (23/45, 51.1%) or the string sign (33/47, 70.2%).
Cyst fluid CEA in combination with cytology and string sign assessment exhibited
the highest accuracy (45/48, 93.8%). Conclusions: Cyst fluid CEA was the most
useful single test for identifying mucinous pancreatic cysts. The addition of
cytology and string sign assessment to cyst fluid CEA increased the overall
accuracy for the diagnosis of mucinous pancreatic cysts.
PMID- 27609485
TI - Clinical Use of Measuring Trough Levels and Antibodies against Infliximab in
Patients with Pediatric Inflammatory Bowel Disease.
AB - Background/Aims: The clinical use of measuring infliximab (IFX) trough levels
(TLs) and antibodies against IFX (ATIs) in patients with pediatric inflammatory
bowel disease (IBD) remains unclear. We propose measuring these variables to
create individual IFX treatment strategies for patients with pediatric IBD.
Methods: This retrospective study was conducted in pediatric patients with IBD
who received IFX from July 2009 to June 2014. Results: Samples were available
from 39 patients with pediatric IBD. A significant difference was observed in IFX
TLs in 16 patients who were in clinical remission (group A) after IFX therapy
(median, 3.99 MUg/ mL; interquartile range [IQR], 0.30 to 21.96) compared to 23
patients who had a poor response to treatment (group B) (median, 0.88 MUg/mL;
IQR, 0.00 to 6.80, p=0.002). In group B, 21 patients underwent empiric
intensification of IFX treatment. After dose intensification, 17 patients had an
improved response to treatment. Four patients still had no response to dose
intensification. Therefore, these patients were switched to other biologics.
Conclusions: Patients who had poor responses and subtherapeutic IFX TLs had an
improved response to dose intensification. Patients who had ATIs were likely to
continue to have no response after dose intensification. Therefore, tailoring
individual IFX treatments based on IFX TLs, ATIs, and the clinical response
should be considered.
PMID- 27609486
TI - Persistent alpha-Fetoprotein Elevation in Healthy Adults and Mutational Analysis
of alpha-Fetoprotein Promoter, Enhancer, and Silencer Regions.
AB - Background/Aims: alpha-Fetoprotein (AFP) is normally <10 ng/mL in adults without
malignancy or liver regeneration. However, hereditary or nonhereditary
persistence of AFP in healthy adults may be encountered in clinical practice.
This study describes four cases of persistent AFP elevation in healthy adults and
investigates mutations in key transcription regulatory regions of the AFP gene as
potential drivers of AFP overexpression. Methods: Four healthy adults with
persistently elevated AFP levels (12.1 to 186.1 ng/mL) for >1 year, and 20
controls with low AFP levels (<0.61 to 2.9 ng/mL) were included in the study. AFP
levels were collected from the families of two of the patients. We sequenced five
regions that are critical for AFP expression: a promoter, two enhancers, and two
silencers. Results: One of the two cases in which family information was
represented is the first case of hereditary persistence of AFP in South Korea.
Mutations related to AFP overexpression were not found in the transcription
regulatory regions among the four patients. Conclusions: Persistent AFP elevation
is a heterogeneous condition with or without a hereditary pattern and may be
caused by factors outside of transcription regulatory region changes. Further
research on the mechanism of AFP elevation is needed.
PMID- 27609488
TI - Lignans and indole alkaloids from the seeds of Centaurea vlachorum Hartvig
(Asteraceae), growing wild in Albania and their biological activity.
AB - The present phytochemical investigation of the seeds of Centaurea vlachorum led
to the isolation and characterisation of four compounds including two indole
alkaloids N-(p-coumaroyl) serotonin (1) and moschamine (2) and two
dibenzylbutyrolactone lignans matairesinol (3) and arctiin (4). This is the first
report on the isolation of non-volatile secondary metabolites from C. vlachorum.
The chemataxonomic significance of these compounds was summarised. Moreover, the
isolated compounds were tested for their free radical scavenging activity using
the following in vitro assays: (i) interaction with the free stable radical of
DPPH (1,1-diphenyl-2-picrylhydrazyl), (ii) inhibition of linoleic acid
peroxidation with the dihydrochloric acid of 2,2-Azobis-2-amidinopropane (AAPH).
Finally, their inhibitory activity towards soybean lipoxygenase was evaluated,
using linoleic acid as substrate.
PMID- 27609489
TI - Nanostructured silicon via metal assisted catalyzed etch (MACE): chemistry
fundamentals and pattern engineering.
AB - There are a range of different methods to generate a nanostructured surface on
silicon (Si) but the most cost effective and optically interesting is the metal
assisted wet chemical etching (MACE) (Koynov et al 2006 Appl. Phys. Lett. 88
203107). MACE of Si is a controllable, room-temperature wet-chemical technique
that uses a thin layer of metal to etch the surface of Si, leaving behind various
nano- and micro-scale surface features or 'black silicon'. MACE-fabricated
nanowires (NWs) provide improved antireflection and light trapping functionality
(Toor et al 2016 Nanoscale 8 15448-66) compared with the traditional 'iso
texturing' (Campbell and Green 1987 J. Appl. Phys. 62 243-9). The resulting lower
reflection and improved light trapping can lead to higher short circuit currents
in NW solar cells (Toor et al 2011 Appl. Phys. Lett. 99 103501). In addition, NW
cells can have higher fill factors and voltages than traditionally processed
cells, thus leading to increased solar cell efficiencies (Cabrera et al 2013 IEEE
J. Photovolt. 3 102-7). MACE NW processing also has synergy with next generation
Si solar cell designs, such as thin epitaxial-Si and passivated emitter rear
contact (Toor et al 2016 Nanoscale 8 15448-66). While several companies have
begun manufacturing black Si, and many more are researching these techniques,
much of the work has not been published in traditional journals and is publicly
available only through conference proceedings and patent publications, which
makes learning the field challenging. There have been three specialized review
articles published recently on certain aspects of MACE or black Si, but do not
present a full review that would benefit the industry (Liu et al 2014 Energy
Environ. Sci. 7 3223-63; Yusufoglu et al 2015 IEEE J. Photovolt. 5 320-8; Huang
et al 2011 Adv. Mater. 23 285-308). In this feature article, we review the
chemistry of MACE and explore how changing parameters in the wet etch process
effects the resulting texture on the Si surface. Then we review efforts to
increase the uniformity and reproducibility of the MACE process, which is
critical for commercializing the black Si technology.
PMID- 27609487
TI - Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of
Helicobacter pylori in Peptic Ulcer Disease.
AB - Background/Aims: The resistance rate of Helicobacter pylori is gradually
increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H.
pylori eradication in peptic ulcer disease. Methods: Between 2002 and 2014, 110
patients in 14 medical centers received levofloxacin-based third-line H. pylori
eradication therapy for peptic ulcer disease. Of these, 88 were included in the
study; 21 were excluded because of lack of follow-up and one was excluded for
poor compliance. Their eradication rates, treatment regimens and durations, and
types of peptic ulcers were analyzed. Results: The overall eradiation rate was
71.6%. The adherence rate was 80.0%. All except one received a proton-pump
inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor,
amoxicillin, levofloxacin, and clarithromycin, and the eradication was
successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days,
and 32 for 14 days. No significant differences were observed in the eradication
rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days,
68.8%, p=0.353). Additionally, no differences were found in the eradiation rates
according to the type of peptic ulcer (gastric ulcer, 73.2% vs
duodenal/gastroduodenal ulcer, 68.8%, p=0.655). Conclusions: Levofloxacin-based
third-line H. pylori eradication showed efficacy similar to that of previously
reported first/second-line therapies.
PMID- 27609490
TI - Low-birth-weight, but not catch-up growth, correlates with insulin resistance and
resistin level in SGA infants at 12 months.
AB - OBJECTIVE: To investigate the insulin resistance status in SGA infants at 12
months and its relationship with auxological and metabolic parameters. METHODS:
One group of 45 SGA and one of 50 appropriate for gestational age infants were
followed from birth to the end of the first year of life. At 12 months, skinfold
thickness, waist circumference, and blood levels of glucose, insulin,
adiponectin, leptin, resistin, visfatin, retinol-binding protein 4, IGFs, lipids
profile were determined, and the HOMA-IR index was calculated. RESULTS: The SGAs
had increased insulin (5.2 +/- 2.7 versus 2.9 +/- 2.4 MUIU/ml, p = 0.012) and
HOMA-IR (1.09 +/- 0.9 versus 0.59 +/- 0.55, p = 0.016). In multiple regression,
insulin resistance indices were independently correlated with low-birth-weight
(beta = -2.92, p = 0.015 for insulin, beta = -2.98, p = 0.011 for HOMA-IR) but
not with catch-up growth in either height or weight or any other metabolic
parameter. Resistin was higher in the SGAs (5.1 +/- 2.1 versus 3.9 +/- 2.1 ng/ml,
p = 0.03) and independently correlated with low-birth-weight but not insulin
resistance. Resistin was negatively correlated with total cholesterol (R = -0.33,
p = 0.007) and positively with lipoprotein(a) (R = 0.49, p = 0.001). CONCLUSION:
Low-birth-weight, but not catch-up growth or adiposity tissue hormones, was
correlated with insulin resistance at 12 months in non-obese SGA infants. The
higher resistin in SGA infants and its correlation with total cholesterol and
lipoprotein(a) need further clarification.
PMID- 27609491
TI - Healthcare Personnel Attire and Devices as Fomites: A Systematic Review.
AB - BACKGROUND Transmission of pathogens within the hospital environment remains a
hazard for hospitalized patients. Healthcare personnel clothing and devices
carried by them may harbor pathogens and contribute to the risk of pathogen
transmission. OBJECTIVE To examine bacterial contamination of healthcare
personnel attire and commonly used devices. METHODS Systematic review. RESULTS Of
1,175 studies screened, 72 individual studies assessed contamination of a variety
of items, including white coats, neckties, stethoscopes, and mobile electronic
devices, with varied pathogens including Staphylococcus aureus, including
methicillin-resistant S. aureus, gram-negative rods, and enterococci.
Contamination rates varied significantly across studies and by device but in
general ranged from 0 to 32% for methicillin-resistant S. aureus and gram
negative rods. Enterococcus was a less common contaminant. Few studies explicitly
evaluated for the presence of Clostridium difficile. Sampling and microbiologic
techniques varied significantly across studies. Four studies evaluated for
possible connection between healthcare personnel contaminants and clinical
isolates with no unequivocally direct link identified. CONCLUSIONS Further
studies to explore the relationship between healthcare personnel attire and
devices and clinical infection are needed. Infect Control Hosp Epidemiol 2016;1
7.
PMID- 27609492
TI - Spot measurement of heart rate based on morphology of PhotoPlethysmoGraphic (PPG)
signals.
AB - Due to increasing health consciousness among people, it is imperative to have low
cost health care devices to measure the vital parameters like heart rate and
arterial oxygen saturation (SpO2). In this paper, an efficient heart rate
monitoring algorithm based on the morphology of photoplethysmography (PPG)
signals to measure the spot heart rate (HR) and its real-time implementation is
proposed. The algorithm does pre-processing and detects the onsets and systolic
peaks of the PPG signal to estimate the heart rate of the subject. Since the
algorithm is based on the morphology of the signal, it works well when the
subject is not moving, which is a typical test case. So, this algorithm is
developed mainly to measure the heart rate at on-demand applications. Real-time
experimental results indicate the heart rate accuracy of 99.5%, mean absolute
percentage error (MAPE) of 1.65%, mean absolute error (MAE) of 1.18 BPM and
reference closeness factor (RCF) of 0.988. The results further show that the
average response time of the algorithm to give the spot HR is 6.85 s, so that the
users need not wait longer to see their HR. The hardware implementation results
show that the algorithm only requires 18 KBytes of total memory and runs at high
speed with 0.85 MIPS. So, this algorithm can be targeted to low-cost embedded
platforms.
PMID- 27609493
TI - Effects of a maternal high-fat diet on offspring behavioral and metabolic
parameters in a rodent model.
AB - Maternal diet-induced obesity can cause detrimental developmental origins of
health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can
lead to later behavioral and metabolic disturbances, but it is not clear which
behaviors and metabolic parameters are most vulnerable. To address this critical
gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may
better replicate most human societies, were used in the current study. About 2
weeks before breeding, adult females were placed on a control or HFD and
maintained on the diets throughout gestation and lactation. F1 offspring were
placed at weaning (30 days of age) on the control diet and spatial learning and
memory, anxiety, exploratory, voluntary physical activity, and metabolic
parameters were tested when they reached adulthood (90 days of age).
Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes
maze trials in male, but not female, offspring. Both male and female HFD-fed
offspring showed increased anxiogenic behaviors, but decreased exploratory and
voluntary physical activity. Moreover, HFD offspring demonstrated lower resting
energy expenditure (EE) compared with controls. Accordingly, HFD offspring
weighed more at adulthood than those from control fed dams, likely the result of
reduced physical activity and EE. Current findings indicate a maternal HFD may
increase obesity susceptibility in offspring due to prenatal programming
resulting in reduced physical activity and EE later in life. Further work is
needed to determine the underpinning neural and metabolic mechanisms by which a
maternal HFD adversely affects neurobehavioral and metabolic pathways in
offspring.
PMID- 27609494
TI - Difference in Composite End Point of Readmission and Death Between Malnourished
and Nonmalnourished Veterans Assessed Using Academy of Nutrition and
Dietetics/American Society for Parenteral and Enteral Nutrition Clinical
Characteristics.
AB - BACKGROUND: Previous studies have demonstrated an association between
malnutrition and poor outcomes. The primary objective of this study was to
explore the difference in the composite end point of readmission rate or
mortality rate between hospitalized veterans with and without malnutrition.
MATERIALS AND METHODS: This was a retrospective chart review comparing veterans
with malnutrition based on a modified version of the Academy of Nutrition and
Dietetics/American Society for Parenteral and Enteral Nutrition consensus
characteristics that used 5 of the 6 clinical characteristics to a matched
control group of nonmalnourished veterans based on age, admitting service, and
date of admission who were admitted between August 1, 2012, and December 1, 2014.
Data were extracted from the medical record. Multivariate analysis was used to
identify predictors of outcomes. RESULTS: In total, 404 patients were included in
the final analysis. All end points were found to be statistically significant.
The malnourished group was more likely to meet the composite end point (odds
ratio [OR], 5.3), more likely to be readmitted within 30 days (OR, 3.4), more
likely to die within 90 days of discharge (OR, 5.5), and more likely to have a
length of stay >7 days (OR, 4.3) compared with the nonmalnourished group. Length
of stay was significantly longer in the malnourished group, 9.80 (11.5) vs 4.38
(4.5) days. CONCLUSION: Malnutrition was an independent risk factor for
readmission within 30 days or death within 90 days of discharge. Malnourished
patients had higher rates of readmission, higher mortality rates, and longer
lengths of stay and were more likely to be discharged to nursing homes.
PMID- 27609495
TI - Toward a personalized response approach in sepsis 4.0.
PMID- 27609497
TI - Novel Technique for Isolating Human Bone Marrow Stem Cells Using Hyaluronic Acid
Hydrogel.
AB - Centrifugation based on density gradients is a general methodology for isolating
human bone marrow (hBM)-derived mesenchymal stem cells (hBMSCs). The mononuclear
cell (MNC) layer can be obtained using a density gradient solution in the
conventional protocol, but it is not suitable for direct transplantation due to
the possible toxicity of this solution. The results obtained are also influenced
by the skill level when applying the technique, which involves time-consuming
processes. We have developed a novel protocol for isolating hBMSCs using
hyaluronic acid (HA), which is the most widely used injectable biomaterial in
clinical settings and a major component of the extracellular matrix. Laying hBM
over the HA and then applying centrifugation yielded three separate layers, with
the HA layer, including MNCs being the most superficial one. Increasing the
volume of HA and/or its crosslinking rate enhanced the yield of MNCs from hBM,
and the cell yield was also significantly higher for a lower centrifugal
acceleration (530 g) than for a higher one (1500 g). Isolated hBMSCs by HA
exhibited similar biological characteristics such as in terms of their
proliferation rate, fibroblast-like morphology, cell-cycle status,
immunophenotype, and multipotency. The use of either type of hBMSC confirmed the
regenerative potential of bone and bone marrow-like tissue in ectopic
transplantation models. This is the first report of a novel protocol for
isolating hBMSCs that utilize HA. We suggest that this novel isolation technique
can be used for the direct application of autogenous MSCs with advantages of
being less time-consuming and involving steps that are easier to perform.
PMID- 27609496
TI - Evaluations of groundwater contamination by leachates around Olusosun open
dumpsite in Lagos metropolis, southwest Nigeria.
AB - A major cause of groundwater pollution in urban areas is contamination by
leachates emanating from municipal solid waste dumpsites. The study evaluated the
quality of water of selected boreholes and wells around Olusosun open solid waste
dumpsite in Lagos metropolis, using water quality index (WQI) rating and
geospatial techniques. Water samples were randomly collected from fifteen
boreholes and five wells downslopes of the dumpsite. The samples were analysed
for the physico-chemical parameters and heavy metals. Factor Analysis was
employed to analyse the information content of the water quality indicators to
determine their appropriateness for indexing. The spatial distribution of the
WQIs determined using Inverse Distance Weighting (IDW) interpolation procedure.
Results showed that the waters were generally acidic with 85% of pH values below
the range suggested by WHO for drinking water. All samples contained
concentration of dissolved oxygen (DO) in quantities higher than the recommended
limit of 2.0 mg/l (average = 4.97 mg/l), while 40% of the samples contained
concentration of K above the recommended limit. The concentration of heavy metals
was generally low. The major cations (Mg, Na, and K) were highly positively
correlated, and were positively correlated with pH, TA, TAL, TH and Cl. Negative
correlations were observed between TDS, NO3(-) and PO4(3-); NO3(-) and Ag; and DO
with the heavy metals. Eighteen parameters consisting of pH, EC, TDS, TA, TAL,
TH, Cl, NO3(-), PO4(3-), Mg, Na, K, Zn, Mn, Fe, Cd, Ag and Pb were found to be
the main indicators of groundwater pollution caused by landfill leachate
percolation. Evaluation of the WQIs indicated that 35% of the water samples were
unsuitable for consumption, while 15%, 15% and 35% were in the good, very good
and excellent categorises, respectively. The degree of suitability of the
borehole and well waters was closely related to proximity to the dumpsite. It is
imperative that appropriate remediation strategies are adopted to forestall
further contamination of the groundwater by leachates in the area.
PMID- 27609498
TI - Comment to 'Magnetic bead detection using nano-transformers'.
PMID- 27609499
TI - Tersicoccus solisilvae sp., nov., a bacterium isolated from forest soil.
AB - A Gram-stain-positive, aerobic, non-motile, coccoid bacterial strain, 36AT, was
isolated from Munnar, in India. Based on the results of 16S rRNA gene sequence
analysis, this strain was identified as representing a member of the genus
Tersicoccus and was most closely related to the type strain of Tersicoccus
phoenicis (98.9 %, sequence similarity), the only other member of the genus, and
to members of the related genus Arthrobacter (<96.1 %, sequence similarity).
However, the DNA-DNA relatedness of strain 36AT with T. phoenicis DSM 30849T was
only 31.9+/-0.8. The DNA G+C content of strain 36AT was 70.9 mol%. Strain 36AT
was an aerobic microbe with optimal growth at 37 degrees C, pH 6.0-8.0 and NaCl
0.5-3 % (w/v). Cell-wall peptidoglycan of strain 36AT was of type A11.20 (Lys-Ser
Ala2). Polar lipids present were phosphatidylglycerol, diphosphatidylglycerol,
phosphatidylinositol, two phospholipids, a glycolipid and four unknown lipids.
The major isoprenoid quinones were MK-9 (H2) and MK-8 (H2). Major fatty acids of
strain 36AT were anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 0.
The results of phylogenetic, chemotaxonomic and biochemical tests allowed a clear
differentiation of strain 36AT, which represents a novel member of the genus
Tersicoccus, for which the name Tersicoccus solisilvae sp. nov., is proposed. The
type strain is 36AT (=KCTC 33776T=CGMCC 1.15480T).
PMID- 27609501
TI - State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major
Depression.
PMID- 27609500
TI - IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjogren's
syndrome reveals molecular markers of Ro/La diversification.
AB - We have used high-resolution mass spectrometry to sequence precipitating anti
Ro60 proteomes from sera of patients with primary Sjogren's syndrome and compare
immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody
subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates
and subjected to combined de novo amino acid sequencing and database matching.
Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of
IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid
substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a
molecular fingerprint of Ro60/La determinant spreading and suggesting that
different forms of Ro60 antigen drive these responses. Sequencing of linked anti
Ro52 proteomes from individual patients and comparison with their anti-Ro60
partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but
with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide
mapping provides insights into Ro/La autoantibody diversification and reveals
serum-based molecular markers of humoral Ro60 autoimmunity.
PMID- 27609502
TI - Performance of a bedside test for tetanus immunity: results of a cross-sectional
study among three EDs in the Netherlands in 2012-2013.
AB - INTRODUCTION: Despite sustained high vaccination coverage and a national
guideline by the Health Council (HC-guideline) on tetanus postexposure
prophylaxis (T-PEP), tetanus sporadically occurs in the Netherlands. This study
aims to assess the added value of a bedside test for tetanus immunity (Tetanos
Quick Stick (TQS); Ingen BioSciences Group, France), in the context of routine T
PEP in two adult cohorts: those born before introduction of tetanus toxoid
vaccination in the National Immunization Programme (NIP) in 1957 (pre-NIP-cohort;
n=196) and those born after (NIP-cohort; n=405). METHODS: Adults included at the
time of visiting one of three participating EDs received T-PEP as per routine
recommendations. Subsequently, a nurse performed the TQS and filled in a
questionnaire. We compared the indication for T-PEP based on TQS results with
those based on the HC-guideline and with actually administration of T-PEP,
stratified by cohort. RESULTS: Among the pre-NIP and NIP-cohort, 16% and 9%,
respectively, received T-PEP, while this was not indicated based on the HC
guideline. Furthermore, 8% and 7%, respectively, did not get T-PEP, although it
was indicated by the guideline. Comparing the indication derived from the HC
guideline with TQS result found that 22% (pre-NIP-cohort) and 8% (NIP-cohort)
were not eligible for T-PEP according to the HC-guideline but had a negative TQS.
Conversely, 36% (pre-NIP-cohort) and 73% (NIP-cohort) were eligible for T-PEP
according to the HC-guideline but had positive TQS, indicating sufficient tetanus
protection. CONCLUSION: Use of the TQS would allow better targeting of T-PEP.
Furthermore, stricter adherence to the HC-guideline can prevent overimmunisation
and decrease the risk of tetanus.
PMID- 27609503
TI - Use of Aldosterone Antagonists for Treatment of Uncontrolled Resistant
Hypertension.
AB - BACKGROUND: Multiple studies indicate that primary aldosteronism (PA) is common
in patients with resistant hypertension, with an estimated prevalence of
approximately 20%. Additional studies suggest that beyond this 20% of patients
with classical PA, there is a larger proportion of patients with lesser degrees
of hyperaldosteronism which contributes even more broadly to antihypertensive
treatment resistance. Given these observations, it is intuitive that use of
aldosterone antagonists will provide antihypertensive benefit in patients with
resistant hypertension and evidence of aldosterone excess. Intriguingly, however,
are clinical findings demonstrating substantive benefit of aldosterone
antagonists in patients with resistant hypertension, but without demonstrative
evidence of hyperaldosteronism, that is, with seemingly normal or even low
aldosterone levels. CONCLUSION: Spironolactone is clearly established as the most
effective fourth agent for treatment of uncontrolled resistant hypertension.
Emerging observations suggest a further role of spironolactone for counteracting
the effects of diet high in sodium, particularly in obese, hypertensive patients.
PMID- 27609505
TI - Managing Hyperkalemia: Stepping Into a New Frontier.
AB - Maintaining potassium balance in the body is essential for cellular function.
Even a slight increase in normal serum potassium levels (3.5-5.0 mEq/L) can
interfere with metabolism, electrical action potentials, and cellular processes.
Hyperkalemia is commonly seen in patients with chronic kidney disease (CKD) and
in patients on renin-angiotensin-aldosterone system (RAAS) inhibitors. Sodium
polystyrene sulfonate (SPS), diuretics, and hemodialysis are currently available
methods for removing potassium from the body; however, these options have their
limitations. Patiromer (Veltassa) and sodium zirconium cyclosilicate are 2 new
therapeutic options that can potentially lead a new frontier in the management of
hyperkalemia. This article will review these novel treatments.
PMID- 27609506
TI - Tension-free vaginal tape-Abbrevo procedure for female stress urinary
incontinence: a prospective analysis over 22 months.
AB - INTRODUCTION: We aimed to study the efficacy and safety of the tension-free
vaginal tape (TVT)-Abbrevo procedure for female stress urinary incontinence
(SUI). METHODS: This was a prospective cohort study that aimed to determine the
subjective and objective cure, improvement of SUI and incidence of complications
among women who underwent TVT-Abbrevo for SUI during a period of 22 months from
September 2011 to June 2013. RESULTS: A total of 76 patients, with a mean age of
48.2 +/- 8.1 years, underwent TVT-Abbrevo during the study period. Among them,
86.8% had vaginal delivery and 5.3% had instrumental delivery. Mean parity was
2.3 +/- 0.8 and mean body mass index was 27.0 +/- 5.0 kg/m2. 11 (14.5%) patients
had previously tried physiotherapy. Mean follow-up duration was 12.3 +/- 5.6
months. The subjective cure rate for SUI at one-month, six-month and one-year
follow-up was 95.7%, 90.8%, and 90.6%, respectively. Among the nine patients who
completed the two-year follow-up, 88.9% reported either cure or improvement of
SUI. At six months, the proportion of patients with objective cure was 86.8%, and
the rates of postoperative groin pain and complications were low. In addition,
overactive bladder symptoms disappeared in 76.3% of patients. CONCLUSION: Our
results are comparable with those of other studies, although long-term results
remain to be seen.
PMID- 27609507
TI - Factors associated with prolonged length of stay in older patients.
AB - INTRODUCTION: Prolonged stay in acute hospitals increases the risk of hospital
acquired infections in older patients, and disrupts patient flow and access to
care due to bed shortages. We aimed to investigate the factors associated with
prolonged length of stay (pLOS) among older patients (aged >= 78 years) in a
tertiary hospital, to identify the potentially modifiable risk factors that could
direct interventions to reduce length of stay (LOS). METHODS: During a three
month period from January 2013 to March 2013, we identified 72 patients with pLOS
(LOS >= 21 days) and compared their demographic and clinical variables with that
of 281 randomly selected control patients (LOS < 21 days) using univariate and
multivariate logistic regression analyses. RESULTS: The mean age of the patients
was 85.30 +/- 5.34 years; 54% of them were female and 72% were of Chinese
ethnicity. Logistic regression revealed the following significant factors for
increased LOS: discharge to intermediate and long-term care services (odds ratio
[OR] 9.22, 95% confidence interval [CI] 3.56-23.89; p < 0.001); increased
severity of illness (OR 2.41, 95% CI 1.12-5.21; p = 0.025); and presence of
caregiver stress (OR 3.85, 95% CI 1.67-8.91; p = 0.002). CONCLUSION: Presence of
caregiver stress and nursing home placement are potential modifiable risk factors
of pLOS among older patients. Early identification and management of caregiver
stress, as well as expediting discharge planning, may help to reduce the length
of stay for this cohort.
PMID- 27609509
TI - Soya milk exerts different effects on plasma amino acid responses and incretin
hormone secretion compared with cows' milk in healthy, young men.
AB - Apart from the well-known action of insulin, the mechanism by which soya and
cows' milk improve postprandial glycaemia control was examined. In total, twelve
healthy, young, Chinese men were studied on three separate occasions, in random
order with isovolumetric (322 ml) control water, soya milk and cows' milk. Plasma
total amino acid concentrations increased 30 min after test meals consumption and
were higher after soya milk (230 %) and cow milk (240 %) consumption compared
with water. Cows' milk ingestion induced higher branched-chain amino acids (BCAA)
(40 %) than soya milk. Postprandial incretin concentrations increased after meal
consumption. Cows' milk meal was accompanied by higher incremental AUC (iAUC)
(170 %) for glucagon-like peptide-1 (GLP-1) compared with soya milk and control
(P=0.06). However, glucose-dependent insulinotropic polypeptide (GIP)
concentrations increased to significantly greater levels after soya milk
consumption (iAUC 60 % higher) compared with cows' milk and control. Consumption
of both soya and cows' milk with carbohydrates induced a similar reduction in
glycaemic response through a different mechanism, beyond insulin action. Plasma
amino acids (alanine and arginine), and incretins in particular (GIP was
stimulated), may be involved in the hyperinsulinaemia after soya milk meals.
However, BCAA and GLP-1 release may be responsible for the reduced glycaemia
after cows' milk consumption by delaying gastric emptying. This could be the
result of different milk protein/amino acid composition, but also differences in
milk carbohydrate composition (i.e. lactose v. sucrose). It can be concluded that
soya milk is a good alternative to cows' milk with regard to glycaemic
regulation, with different mechanisms involved.
PMID- 27609511
TI - A 3-Month-Old Infant With Lethargy and Metabolic Acidosis.
PMID- 27609510
TI - A novel method for predicting activity of cis-regulatory modules, based on a
diverse training set.
AB - MOTIVATION: With the rapid emergence of technologies for locating cis-regulatory
modules (CRMs) genome-wide, the next pressing challenge is to assign precise
functions to each CRM, i.e. to determine the spatiotemporal domains or cell-types
where it drives expression. A popular approach to this task is to model the
typical k-mer composition of a set of CRMs known to drive a common expression
pattern, and assign that pattern to other CRMs exhibiting a similar k-mer
composition. This approach does not rely on prior knowledge of transcription
factors relevant to the CRM or their binding motifs, and is thus more widely
applicable than motif-based methods for predicting CRM activity, but is also
prone to false positive predictions. RESULTS: We present a novel strategy to
improve the above-mentioned approach: to predict if a CRM drives a specific gene
expression pattern, assess not only how similar the CRM is to other CRMs with
similar activity but also to CRMs with distinct activities. We use a state-of-the
art statistical method to quantify a CRM's sequence similarity to many different
training sets of CRMs, and employ a classification algorithm to integrate these
similarity scores into a single prediction of the CRM's activity. This strategy
is shown to significantly improve CRM activity prediction over current
approaches. AVAILABILITY AND IMPLEMENTATION: Our implementation of the new
method, called IMMBoost, is freely available as source code, at
https://github.com/weiyangedward/IMMBoost CONTACT:
sinhas@illinois.eduSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27609508
TI - The Singapore Myeloma Study Group Consensus Guidelines for the management of
patients with multiple myeloma.
AB - Multiple myeloma (MM) is an incurable plasma cell neoplasm with an incidence of
100 patients per year in Singapore. Major advances have been made in the
diagnosis, risk stratification and treatment of MM in the recent past. The
reclassification of a subset of patients with smouldering MM, based on high-risk
biomarkers, and the development of the revised international staging system are
among the key new developments in diagnosis and staging. The use of novel agent
based treatment has resulted in significant improvements in the survival and
quality of life of many patients with MM. Determining the optimal use of
proteasome inhibitors, immunomodulators and, more recently, monoclonal antibodies
is an area of ongoing investigation. In this guideline, we aim to provide an
overview of the management of MM, incorporating the latest developments in
diagnosis and treatment.
PMID- 27609512
TI - Probiotics-To Use, or Not to Use? An Updated Meta-analysis.
PMID- 27609513
TI - Human Papillomavirus Vaccination and Age at First Sexual Activity, National
Health and Nutrition Examination Survey.
AB - The National Health and Nutrition Examination Survey (NHANES) collects
information on human papillomavirus (HPV) vaccination history as well as sexual
activity. We evaluated data from NHANES to assess report of HPV vaccination with
>=1 dose and 3 doses among females and males aged 11 to 26 years during 2007
2014. We also examined age at first vaccine dose and age at first sexual activity
among females aged 14 to 26 years. Vaccination significantly increased in females
aged 13 to 26 years, but not among 11- to 12-year-old girls, and remained low for
both females and males. In NHANES 2011-2014, among females with known age at
first vaccine dose, 43.1% reported having had sex before or in the same year they
received their first HPV vaccine, and this varied by race/ethnicity. Clinicians
should provide strong recommendations consistent with guidelines, including
routine vaccination of girls and boys at age 11 or 12 years.
PMID- 27609514
TI - Structural Basis for High Specificity of Amadori Compound and Mannopine Opine
Binding in Bacterial Pathogens.
AB - Agrobacterium tumefaciens pathogens genetically modify their host plants to drive
the synthesis of opines in plant tumors. Opines are either sugar phosphodiesters
or the products of condensed amino acids with ketoacids or sugars. They are
Agrobacterium nutrients and imported into the bacterial cell via periplasmic
binding proteins (PBPs) and ABC-transporters. Mannopine, an opine from the
mannityl-opine family, is synthesized from an intermediate named deoxy-fructosyl
glutamine (DFG), which is also an opine and abundant Amadori compound (a name
used for any derivative of aminodeoxysugars) present in decaying plant materials.
The PBP MotA is responsible for mannopine import in mannopine-assimilating
agrobacteria. In the nopaline-opine type agrobacteria strain, SocA protein was
proposed as a putative mannopine binding PBP, and AttC protein was annotated as a
mannopine binding-like PBP. Structural data on mannityl-opine-PBP complexes is
currently lacking. By combining affinity data with analysis of seven x-ray
structures at high resolution, we investigated the molecular basis of MotA, SocA,
and AttC interactions with mannopine and its DFG precursor. Our work demonstrates
that AttC is not a mannopine-binding protein and reveals a specific binding
pocket for DFG in SocA with an affinity in nanomolar range. Hence, mannopine
would not be imported into nopaline-type agrobacteria strains. In contrast, MotA
binds both mannopine and DFG. We thus defined one mannopine and two DFG binding
signatures. Unlike mannopine-PBPs, selective DFG-PBPs are present in a wide
diversity of bacteria, including Actinobacteria, alpha-,beta-, and gamma
proteobacteria, revealing a common role of this Amadori compound in pathogenic,
symbiotic, and opportunistic bacteria.
PMID- 27609515
TI - Biochemical Foundations of Health and Energy Conservation in Hibernating Free
ranging Subadult Brown Bear Ursus arctos.
AB - Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking,
urinating, and defecating at a metabolic rate of only 25% of the summer activity
rate. Nonetheless, they emerge healthy and alert in spring. We quantified the
biochemical adaptations for hibernation by comparing the proteome, metabolome,
and hematological features of blood from hibernating and active free-ranging
subadult brown bears with a focus on conservation of health and energy. We found
that total plasma protein concentration increased during hibernation, even though
the concentrations of most individual plasma proteins decreased, as did the white
blood cell types. Strikingly, antimicrobial defense proteins increased in
concentration. Central functions in hibernation involving the coagulation
response and protease inhibition, as well as lipid transport and metabolism, were
upheld by increased levels of very few key or broad specificity proteins. The
changes in coagulation factor levels matched the changes in activity
measurements. A dramatic 45-fold increase in sex hormone-binding globulin levels
during hibernation draws, for the first time, attention to its significant but
unknown role in maintaining hibernation physiology. We propose that energy for
the costly protein synthesis is reduced by three mechanisms as follows: (i)
dehydration, which increases protein concentration without de novo synthesis;
(ii) reduced protein degradation rates due to a 6 degrees C reduction in body
temperature and decreased protease activity; and (iii) a marked redistribution of
energy resources only increasing de novo synthesis of a few key proteins. The
comprehensive global data identified novel biochemical strategies for bear
adaptations to the extreme condition of hibernation and have implications for our
understanding of physiology in general.
PMID- 27609517
TI - TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet
Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk.
AB - Protein-tyrosine phosphatase TULA-2 has been shown to regulate receptor signaling
in several cell types, including platelets. Platelets are critical for
maintaining vascular integrity; this function is mediated by platelet aggregation
in response to recognition of the exposed basement membrane collagen by the GPVI
receptor, which is non-covalently associated with the signal-transducing FcRgamma
polypeptide chain. Our previous studies suggested that TULA-2 plays an important
role in negatively regulating signaling through GPVI-FcRgamma and indicated that
the tyrosine-protein kinase Syk is a key target of the regulatory action of TULA
2 in platelets. However, the molecular basis of the down-regulatory effect of
TULA-2 on Syk activation via FcRgamma remained unclear. In this study, we
demonstrate that suppression of Syk activation by TULA-2 is mediated, to a
substantial degree, by dephosphorylation of Tyr(P)346, a regulatory site of Syk,
which becomes phosphorylated soon after receptor ligation and plays a critical
role in initiating the process that yields fully activated Syk. TULA-2 is capable
of dephosphorylating Tyr(P)346 with high efficiency, thus controlling the overall
activation of Syk, but is less efficient in dephosphorylating other regulatory
sites of this kinase. Therefore, dephosphorylation of Tyr(P)346 may be considered
an important "checkpoint" in the regulation of Syk activation process. Putative
biological functions of TULA-2-mediated dephosphorylation of Tyr(P)346 may
include deactivation of receptor-activated Syk or suppression of Syk activation
by suboptimal stimulation.
PMID- 27609516
TI - Single-molecule Imaging Analysis of Binding, Processive Movement, and
Dissociation of Cellobiohydrolase Trichoderma reesei Cel6A and Its Domains on
Crystalline Cellulose.
AB - Trichoderma reesei Cel6A (TrCel6A) is a cellobiohydrolase that hydrolyzes
crystalline cellulose into cellobiose. Here we directly observed the reaction
cycle (binding, surface movement, and dissociation) of single-molecule intact
TrCel6A, isolated catalytic domain (CD), cellulose-binding module (CBM), and CBM
and linker (CBM-linker) on crystalline cellulose Ialpha The CBM-linker showed a
binding rate constant almost half that of intact TrCel6A, whereas those of the CD
and CBM were only one-tenth of intact TrCel6A. These results indicate that the
glycosylated linker region largely contributes to initial binding on crystalline
cellulose. After binding, all samples showed slow and fast dissociations, likely
caused by the two different bound states due to the heterogeneity of cellulose
surface. The CBM showed much higher specificity to the high affinity site than to
the low affinity site, whereas the CD did not, suggesting that the CBM leads the
CD to the hydrophobic surface of crystalline cellulose. On the cellulose surface,
intact molecules showed slow processive movements (8.8 +/- 5.5 nm/s) and fast
diffusional movements (30-40 nm/s), whereas the CBM-Linker, CD, and a
catalytically inactive full-length mutant showed only fast diffusional movements.
These results suggest that both direct binding and surface diffusion contribute
to searching of the hydrolysable point of cellulose chains. The duration time
constant for the processive movement was 7.7 s, and processivity was estimated as
68 +/- 42. Our results reveal the role of each domain in the elementary steps of
the reaction cycle and provide the first direct evidence of the processive
movement of TrCel6A on crystalline cellulose.
PMID- 27609518
TI - HIV-1 Tat Promotes Lysosomal Exocytosis in Astrocytes and Contributes to
Astrocyte-mediated Tat Neurotoxicity.
AB - Tat interaction with astrocytes has been shown to be important for Tat
neurotoxicity and HIV/neuroAIDS. We have recently shown that Tat expression leads
to increased glial fibrillary acidic protein (GFAP) expression and aggregation
and activation of unfolded protein response/endoplasmic reticulum (ER) stress in
astrocytes and causes neurotoxicity. However, the exact molecular mechanism of
astrocyte-mediated Tat neurotoxicity is not defined. In this study, we showed
that neurotoxic factors other than Tat protein itself were present in the
supernatant of Tat-expressing astrocytes. Two-dimensional gel electrophoresis and
mass spectrometry revealed significantly elevated lysosomal hydrolytic enzymes
and plasma membrane-associated proteins in the supernatant of Tat-expressing
astrocytes. We confirmed that Tat expression and infection of pseudotyped HIV.GFP
led to increased lysosomal exocytosis from mouse astrocytes and human astrocytes.
We found that Tat-induced lysosomal exocytosis was tightly coupled to astrocyte
mediated Tat neurotoxicity. In addition, we demonstrated that Tat-induced
lysosomal exocytosis was astrocyte-specific and required GFAP expression and was
mediated by ER stress. Taken together, these results show for the first time that
Tat promotes lysosomal exocytosis in astrocytes and causes neurotoxicity through
GFAP activation and ER stress induction in astrocytes and suggest a common
cascade through which aberrant astrocytosis/GFAP up-regulation potentiates
neurotoxicity and contributes to neurodegenerative diseases.
PMID- 27609521
TI - Frequency-resolved optical gating measurement of ultrashort pulses by using
single nanowire.
AB - The use of ultrashort pulses for fundamental studies and applications has been
increasing rapidly in the past decades. Along with the development of ultrashort
lasers, exploring new pulse diagnositic approaches with higher signal-to-noise
ratio have attracted great scientific and technological interests. In this work,
we demonstrate a simple technique of ultrashort pulses characterization with a
single semiconductor nanowire. By performing a frequency-resolved optical gating
method with a ZnO nanowire coupled to tapered optical microfibers, the phase and
amplitude of a pulse series are extracted. The generated signals from the
transverse frequency conversion process can be spatially distinguished from the
input, so the signal-to-noise ratio is improved and permits lower energy pulses
to be identified. Besides, since the nanometer scale of the nonlinear medium
provides relaxed phase-matching constraints, a measurement of 300-nm-wide
supercontinuum pulses is achieved. This system is highly compatible with standard
optical fiber systems, and shows a great potential for applications such as on
chip optical communication.
PMID- 27609519
TI - Exploring Intein Inhibition by Platinum Compounds as an Antimicrobial Strategy.
AB - Inteins, self-splicing protein elements, interrupt genes and proteins in many
microbes, including the human pathogen Mycobacterium tuberculosis Using conserved
catalytic nucleophiles at their N- and C-terminal splice junctions, inteins are
able to excise out of precursor polypeptides. The splicing of the intein in the
mycobacterial recombinase RecA is specifically inhibited by the widely used
cancer therapeutic cisplatin, cis-[Pt(NH3)2Cl2], and this compound inhibits
mycobacterial growth. Mass spectrometric and crystallographic studies of Pt(II)
binding to the RecA intein revealed a complex in which two platinum atoms bind at
N- and C-terminal catalytic cysteine residues. Kinetic analyses of NMR
spectroscopic data support a two-step binding mechanism in which a Pt(II) first
rapidly interacts reversibly at the N terminus followed by a slower, first order
irreversible binding event involving both the N and C termini. Notably, the
ligands of Pt(II) compounds that are required for chemotherapeutic efficacy and
toxicity are no longer bound to the metal atom in the intein adduct. The lack of
ammine ligands and need for phosphine represent a springboard for future design
of platinum-based compounds targeting inteins. Because the intein splicing
mechanism is conserved across a range of pathogenic microbes, developing these
drugs could lead to novel, broad range antimicrobial agents.
PMID- 27609524
TI - A robust approach for trajectory tracking control of a quadrotor with
experimental validation.
AB - In this paper, a new control scheme for motion control of quadrotors is
presented. The proposed model based controller makes use of simple estimations of
vehicle parameters. Besides, the controller is developed under properties of the
vehicle model. A rigorous analysis is developed to prove that the closed-loop
system trajectories are uniformly ultimately bounded. The validity of the
proposed control scheme is tested by numerical simulations and experimental
results. This validation shows that the proposed controller guarantees that the
quadrotor performs tracking of a desired pose (position and orientation)
trajectory with good accuracy. The new scheme has been compared with respect to
other robust controllers. The results indicate better tracking accuracy for the
new scheme.
PMID- 27609520
TI - HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in
Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein
(GFAP) Activation and Aggregation.
AB - HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks
of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by
increased cytoplasmic accumulation of the intermediate filament glial fibrillary
acidic protein (GFAP). We have shown that that Tat induces GFAP expression in
astrocytes and that GFAP activation is indispensable for astrocyte-mediated Tat
neurotoxicity. However, the underlying molecular mechanisms are not known. In
this study, we showed that Tat expression or GFAP expression led to formation of
GFAP aggregates and induction of unfolded protein response (UPR) and endoplasmic
reticulum (ER) stress in astrocytes. In addition, we demonstrated that GFAP up
regulation and aggregation in astrocytes were necessary but also sufficient for
UPR/ER stress induction in Tat-expressing astrocytes and for astrocyte-mediated
Tat neurotoxicity. Importantly, we demonstrated that inhibition of Tat- or GFAP
induced UPR/ER stress by the chemical chaperone 4-phenylbutyrate significantly
alleviated astrocyte-mediated Tat neurotoxicity in vitro and in the brain of Tat
expressing mice. Taken together, these results show that HIV-1 Tat expression
leads to UPR/ER stress in astrocytes, which in turn contributes to astrocyte
mediated Tat neurotoxicity, and raise the possibility of developing HIV/neuroAIDS
therapeutics targeted at UPR/ER stress.
PMID- 27609522
TI - Restoration of enterohepatic bile acid pathways in pregnant mice following short
term activation of Fxr by GW4064.
AB - The farnesoid X receptor (Fxr) controls bile acid homeostasis by coordinately
regulating the expression of synthesizing enzymes (Cyp7a1, Cyp8b1), conjugating
enzymes (Bal, Baat) and transporters in the ileum (Asbt, Ostalpha/beta) and liver
(Ntcp, Bsep, Ostbeta). Transcriptional regulation by Fxr can be direct, or
through the ileal Fgf15/FGF19 and hepatic Shp pathways. Circulating bile acids
are increased during pregnancy due to hormone-mediated disruption of Fxr
signaling. While this adaptation enhances lipid absorption, elevated bile acids
may predispose women to develop maternal cholestasis. The objective of this study
was to determine whether short-term treatment of pregnant mice with GW4064 (a
potent FXR agonist) restores Fxr signaling to the level observed in virgin mice.
Plasma, liver and ilea were collected from virgin and pregnant mice administered
vehicle or GW4064 by oral gavage. Treatment of pregnant mice with GW4064 induced
ileal Fgf15, Shp and Ostalpha/beta mRNAs, and restored hepatic Shp, Bal, Ntcp,
and Bsep back to vehicle-treated virgin levels. Pregnant mice exhibited 2.5-fold
increase in Cyp7a1 mRNA compared to virgin controls, which was reduced by GW4064.
Similarly treatment of mouse primary hepatocytes with plasma isolated from
pregnant mice induced Cyp7a1 mRNA by nearly 3-fold as compared to virgin plasma,
which could be attenuated by co-treatment with either GW4064 or recombinant FGF19
protein. Collectively, these data reveal that repressed activity of intestinal
and hepatic Fxr in pregnancy, as previously demonstrated, may be restored by
pharmacological activation. This study provides the basis for a novel approach to
restore bile acid homeostasis in patients with maternal cholestasis.
PMID- 27609526
TI - On Blastocystis secreted cysteine proteases: a legumain-activated cathepsin B
increases paracellular permeability of intestinal Caco-2 cell monolayers.
AB - Blastocystis spp. pathogenic potential remains unclear as these anaerobic
parasitic protozoa are frequently isolated from stools of both symptomatic and
asymptomatic subjects. In silico analysis of the whole genome sequence of
Blastocystis subtype 7 revealed the presence of numerous proteolytic enzymes
including cysteine proteases predicted to be secreted. To assess the potential
impact of proteases on intestinal cells and gut function, we focused our study on
two cysteine proteases, a legumain and a cathepsin B, which were previously
identified in Blastocystis subtype 7 culture supernatants. Both cysteine
proteases were produced as active recombinant proteins. Activation of the
recombinant legumain was shown to be autocatalytic and triggered by acidic pH,
whereas proteolytic activity of the recombinant cathepsin B was only recorded
after co-incubation with the legumain. We then measured the diffusion of 4-kDa
FITC-labelled dextran across Caco-2 cell monolayers following exposition to
either Blastocystis culture supernatants or each recombinant protease. Both
Blastocystis culture supernatants and recombinant activated cathepsin B induced
an increase of Caco-2 cell monolayer permeability, and this effect was
significantly inhibited by E-64, a specific cysteine protease inhibitor. Our
results suggest that cathepsin B might play a role in pathogenesis of
Blastocystis by increasing intestinal cell permeability.
PMID- 27609525
TI - Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive
behavioural therapy in out-patients with anorexia nervosa.
AB - BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial
morbidity and mortality. The treatment of AN very often is protracted; repeated
hospitalizations and lost productivity generate substantial economic costs in the
health care system. Therefore, this study aimed to determine the differential
cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT),
enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual
(TAU-O) in the treatment of adult women with AN. METHOD: The analysis was
conducted alongside the randomized controlled Anorexia Nervosa Treatment of
OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs
per recovery at 22 months post-randomization (n = 156). Unadjusted incremental
cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness
acceptability curves (CEACs) adjusted net-benefit regressions were applied
assuming different values for the maximum willingness to pay (WTP) per additional
recovery. Cost-utility and assumptions underlying the base case were investigated
in exploratory analyses. RESULTS: Costs of in-patient treatment and the
percentage of patients who required in-patient treatment were considerably lower
in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be
dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E.
CEACs showed that the probability for cost-effectiveness of FTP compared with TAU
O and CBT-E was ?95% if the WTP per recovery was ??9825 and ??24 550,
respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective
remained <90% for all WTPs. The exploratory analyses showed similar but less
pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective
in the treatment of adult AN.
PMID- 27609528
TI - Reducing Surgical Site Infection with Negative-Pressure Wound Therapy After Open
Abdominal Surgery: A Prospective Randomized Controlled Study.
AB - BACKGROUND AND AIMS: Surgical site infection, in particular superficial incision
infection, is a common type of complication following abdominal surgery. Negative
pressure wound therapy has been confirmed to reduce the incidence of surgical
site infection in various surgeries, but there are few prospective randomized
studies into its application to abdominal surgery. MATERIAL AND METHODS: A
prospective randomized controlled study was conducted in which patients with
abdominal surgery and open surgery were randomly divided into a negative-pressure
wound therapy experimental group and a gauze-covering control group. Information
about demographic data, type of surgery, surgical sites, incision treatment
outcomes, surgical site infection factors, and follow-up was recorded. RESULTS:
From May 2015 to December 2015, 71 patients were enrolled in this study,
including 33 in the experimental group and 38 in the control group. There were 10
cases of incision complications, all superficial infections, with an incidence of
14.1%. The surgical site infection incidence was statistically different between
the experimental and control groups (3.0% vs 23.7%, p = 0.031). Multivariate
logistic regression analysis showed that incision length ?20 cm increased the
surgical site infection incidence (odds ratio value of 15.576, p = 0.004) and
that the application of negative-pressure wound therapy reduced the surgical site
infection incidence (odds ratio value of 0.073, p = 0.029). CONCLUSION: Negative
pressure wound therapy can reduce the incidence of surgical site infection in
open abdominal surgery.
PMID- 27609527
TI - Roles and regulation of autophagy and apoptosis in the remodelling of the
lepidopteran midgut epithelium during metamorphosis.
AB - We previously showed that autophagy and apoptosis occur in the removal of the
lepidopteran larval midgut during metamorphosis. However, their roles in this
context and the molecular pathways underlying their activation and regulation
were only hypothesized. The results of the present study better clarify the
timing of the activation of these two processes: autophagic and apoptotic genes
are transcribed at the beginning of metamorphosis, but apoptosis intervenes after
autophagy. To investigate the mechanisms that promote the activation of autophagy
and apoptosis, we designed a set of experiments based on injections of 20
hydroxyecdysone (20E). Our data demonstrate that autophagy is induced at the end
of the last larval stage by the 20E commitment peak, while the onset of apoptosis
occurs concomitantly with the 20E metamorphic peak. By impairing autophagic flux,
the midgut epithelium degenerated faster, and higher caspase activity was
observed compared to controls, whereas inhibiting caspase activation caused a
severe delay in epithelial degeneration. Our data demonstrate that autophagy
plays a pro-survival function in the silkworm midgut during metamorphosis, while
apoptosis is the major process that drives the demise of the epithelium. The
evidence collected in this study seems to exclude the occurrence of autophagic
cell death in this setting.
PMID- 27609529
TI - Faecal and Serum Metabolomics in Paediatric Inflammatory Bowel Disease.
AB - Background: Inflammatory bowel disease [IBD] is considered to result from the
interplay between host and intestinal microbiota but its pathogenesis is
incompletely understood. While IBD in adults has shown to be associated with
marked changes in body fluid metabolomics, there are only few studies in
children. Hence, this prospective study addressed the faecal and serum
metabolomics in newly diagnosed paediatric IBD. Methods: Paediatric patients with
IBD undergoing diagnostic endoscopies and controls also with endoscopy but no
signs of inflammation provided blood and stool samples in a tertiary care
hospital. Blood inflammatory markers and faecal calprotectin levels were
determined. The serum and faecal metabolomics were determined using ultra-high
pressure liquid chromatography coupled to a mass spectrometer. Results: Serum and
faecal metabolite profiles in newly diagnosed paediatric IBD patients were
different from healthy controls and categorized Crohn's disease and ulcerative
colitis [UC] patients into separate groups. In serum, amino acid metabolism,
folate biosynthesis and signalling pathways were perturbed in Crohn's disease; in
UC also sphingolipid metabolic pathways were perturbed when compared to controls.
In faecal samples, there was an increased level of several metabolites in UC in
contrast to low or intermediate levels in Crohn's disease. There was a clear
correlation with the level of inflammation, i.e. faecal calprotectin levels and
the profile of various biologically important metabolites [carnosine, ribose and,
most significantly, choline]. Conclusion: Characterization of inflammatory
pattern using metabolomics analysis is a promising tool for better understanding
disease pathogenesis of paediatric IBD.
PMID- 27609530
TI - Medial and mediolateral orbital decompression in intractable Graves' Orbitopathy.
AB - OBJECTIVE: Graves' Orbitopathy (GO) has well established treatment guidelines;
however, its management is still controversial. The aim was to evaluate the
results of medial and mediolateral orbital decompression (OD) in intractable GO.
METHODS: Retrospective chart review of all patients with advanced stages of GO,
who underwent medial (1-wall) or mediolateral (2-wall) OD between May 2012 and
November 2014 in our institution. Ophthalmologic examinations included visual
acuity, Hertel exophthalmometry (proptosis), intraocular pressure (IOP), visual
field (30:2) and diplopia. Follow-up was performed 1 week, 3 months and 1 year
postoperatively. Additionally, a questionnaire was used to investigate subjective
benefits. RESULTS: The study included 34 eyes of 20 patients. In our study, GO
patients who underwent mediolateral OD had significantly higher IOP
preoperatively (p<0.05) and lower visual acuity, proptosis and visual field
compared with patients who underwent medial OD. After 1- and 2-wall OD, visual
acuity, proptosis, visual field and IOP in upgaze improved significantly. Using a
questionnaire, the patients reported significant improvements in impaired vision,
eye pain and pressure, vitality and social life. 94% of all patients reported
they would repeat the operation. After 2-wall OD, the surgical scar had little
effect. CONCLUSION: With GO patients in advanced stages, both medial (1-wall) and
mediolateral (2-wall) OD procedures are convincing therapeutic options. In more
advanced GO stages with high IOP, 2-wall OD should be prioritized, as
mediolateral OD had superior long-term functional outcomes.
PMID- 27609532
TI - Harder-to-reach people living with HIV experiencing high prevalence of all-type
mental health disorder diagnosis.
AB - People living with HIV/AIDS (PHA) often concurrently cope with mental health
disorders that may greatly influence HIV and other health-related outcomes. The
objective of this study was to examine the prevalence and correlates of self
reported mental health disorder diagnosis among a cohort of harder-to-reach HIV
positive individuals in British Columbia, Canada. Between 2007 and 2010, 1000 PHA
who had initiated ART were enrolled in the Longitudinal Investigation into
Supportive and Ancillary health services (LISA) study. Socio-demographic,
behavioral, health-care utilization and psychosocial information was collected
through interviewer-led questionnaires and linked to longitudinal clinical
variables through the provincial Drug Treatment Program at the BC Centre for
Excellence in HIV/AIDS. We identified the prevalence of all-type and specific
mental health disorders among this population. Of the 916 participants included
in this analysis, 494 (54%) reported ever having a mental health disorder
diagnosis. Mood (85%) and anxiety (65%) disorders were the two most frequently
reported mental health conditions. Self-reported all-type mental health disorder
was independently associated with decreased overall functioning (adjusted odds
ratio [AOR] = 0.90, 95% confidence interval [CI] = 0.83-0.98) and life
satisfaction (AOR = 0.81, 95% CI = 0.74-0.89), and having higher stigma score
(AOR = 1.11, 95%CI = 1.02-1.21). Participants reporting any mental health
disorder were more likely to report a history of sexual assault (AOR = 2.45, 95%
CI = 1.75-3.43) and to have used case management services (AOR = 1.63, 95%CI =
1.17-2.27). Our findings uncovered a high burden of mental health disorders among
harder-to-reach PHA and suggest that PHA with at least one mental health disorder
diagnosis are disproportionately impacted by sexual violence and stigma.
PMID- 27609533
TI - Lettuce Allergy Is a Lipid Transfer Syndrome-Related Food Allergy With a High
Risk of Severe Reactions.
AB - BACKGROUND AND OBJECTIVE: Lipid transfer protein (LTP) sensitization is the most
common cause of food allergy in the Mediterranean area, with peach allergy acting
as the primary sensitizer in most cases. Lettuce has been described as a common
offending food in patients with LTP syndrome. The aim of the study was to
investigate the frequency and clinical expression of LTP syndrome in a sample of
lettuceallergic patients. METHODS: We determined specific IgE to Pru p 3 and
lettuce in a sample of 30 patients with a diagnosis of lettuce allergy. Symptoms
elicited by other LTP-containing plant-derived foods and the presence of
cofactors were assessed. RESULTS: The clinical symptoms of lettuce allergy were
frequently severe, with 18 of the 30 patients experiencing anaphylaxis. All the
patients had allergic reactions to other plant foods. Cofactors were involved in
the clinical reactions of 13 of the 30 patients. Sensitization to pollens was
found in 90% of patients. CONCLUSIONS: Lettuce allergy is found not as an
isolated condition but in the context of LTP syndrome and it is characterized by
severe reactions and frequent cofactor association.
PMID- 27609534
TI - Extensive characterization of a lentiviral-derived stable cell line expressing
rabbit hemorrhagic disease virus VPg protein.
AB - Rabbit hemorrhagic disease virus (RHDV) is an important member of the
caliciviridae family. Currently, no suitable tissue culture system is available
for proliferating RHDV, which limits the study of its pathogenesis. To bypass
this obstacle, we established a cell line, RK13-VPg, stably expressing the VPg
gene with a lentivirus packaging system in this study. In addition, the recently
constructed RHDV replicon in our laboratory provided an appropriate model for
studying the pathogenesis of RHDV without in vitro RHDV propagation and culture.
Using this RHDV replicon and RK13-VPg cell line, we further demonstrated that the
presence of VPg protein is essential for efficient translation of an RHDV
replicon. Therefore, the RK13-VPg cell line is a powerful tool for studying the
replication and translation mechanisms of RHDV.
PMID- 27609537
TI - Dausset J, Colombani J, Legrand L, Feingold N, Rapaport FT. Genetic and
biological aspects of the HL-A system of human histocompatibility. Blood.
1970;35(5):591-612.
PMID- 27609535
TI - Field evaluation of an open and polyvalent universal HIV-1/SIVcpz/SIVgor
quantitative RT-PCR assay for HIV-1 viral load monitoring in comparison to Abbott
RealTime HIV-1 in Cameroon.
AB - With the increasing demand of HIV viral load (VL) tests in resource-limited
countries (RLCs) there is a need for assays at affordable cost and able to
quantify all known HIV-1 variants. VLs obtained with a recently developed open
and polyvalent universal HIV-1/SIVcpz/SIVgor RT-qPCR were compared to Abbott
RealTime HIV-1 assay in Cameroon. On 474 plasma samples, characterized by a wide
range of VLs and a broad HIV-1 group M genetic diversity, 97.5% concordance was
observed when using the lower detection limit of each assay. When using the
threshold of 3.00 log10 copies/mL, according to WHO guidelines to define
virological failure (VF) in RLCs, the concordance was 94.7%, 360/474 versus
339/474 patients were identified with VF with the new assay and Abbott RealTime
HIV-1, respectively. Higher VLs were measured with the new assay, +0.47 log10
copies/mL (95% CI; 0.42-0.52) as shown with Bland-Altman analysis. Eleven samples
from patients on VF with drug resistance were not detected by Abbott RealTime HIV
1 versus two only with the new assay. Overall, our study showed that the new
assay can be easily implemented in a laboratory in RLCs with VL experience and
showed good performance on a wide diversity of HIV-1 group M variants.
PMID- 27609538
TI - Nodal marginal zone mutational signature.
PMID- 27609536
TI - Uptake and attitudes regarding hepatitis A vaccine among childcare centre staff,
administrators, and parents.
AB - OBJECTIVES: Study objectives were to assess parents' and childcare agency staff's
uptake of and attitudes/beliefs related to hepatitis A vaccine. STUDY DESIGN:
Cross-sectional survey. METHODS: Questionnaires were administered to parents and
staff in 23 St. Louis childcare agencies between September and December 2014.
Categorical data were compared using Chi-squared test. Multivariate logistic
regression, stratified by staff vs parents, was used to find predictors of
hepatitis A vaccine uptake. RESULTS: In total, 351 staff and parents participated
(response rate = 32%). More staff than parents had been offered or recommended to
receive hepatitis A vaccine by a healthcare provider (55.4% vs 36.6% and 53.3% vs
28.7%, respectively; P = .001 for both). More staff than parents received
hepatitis A vaccine (85.3% vs 67.5%, Chi-squared test = 11.0, P < .001).
Predictors of staff vaccine uptake included being aware of CDC vaccination
recommendations (OR = 11.2, CI = [1.4-91], P < .05), employer recommendation to
get vaccinated (OR = 8.1, CI = [1.8-36.8], P < .01), and having a mandatory staff
vaccination policy (OR = 4.8, CI = [1.2-19.7], P < .05). Predictors of parent
vaccine uptake included being offered the vaccine by a healthcare provider (OR =
4.3, CI = [1.3-4.9], P < .001), being aware of the CDC vaccination
recommendations (OR = 4.0, CI = [2.0-8.0], P < .001), and having received
influenza vaccine previously (OR = 2.5, CI = [1.3-4.9], P < .01). CONCLUSION: In
this study population, many childcare agency staff and parents have received
hepatitis A vaccine, though staff immunization rates are at the minimum needed to
reach herd immunity levels. Having employers encourage vaccination, offer free
vaccine, or make vaccine available onsite could increase staff vaccination rates.
Public health should partner with childcare agencies to increase staff vaccine
uptake, which could result in community herd immunity.
PMID- 27609539
TI - Cotargeting BCL-2 and BCL-XL for maximal efficacy in ALL.
PMID- 27609540
TI - Putting it all together in CMML risk stratification.
PMID- 27609541
TI - The effect of optimal space allowance on growth performance and physiological
responses of pigs at different stages of growth.
AB - This study was conducted to determine the optimal space allowance for maximizing
the growth performance of pigs at each of the following five growth stages (based
on BW ranges): stage 1, 11 to 25 kg BW; stage 2, 25 to 45 kg BW; stage 3, 45 to
65 kg BW; stage 4, 65 to 85 kg BW; and stage 5, 85 to 110 kg BW. A total of 1590
crossbred (Landrace*Yorkshire*Duroc) pigs were assigned to one of four treatments
at each growth stage, with three replicates each. Pen areas at each growth stage
were 6, 11, 16, 19.5 and 20 m2 for stages 1 to 5, respectively. Space allowances
for the four treatments at each growth stage were modified by varying the number
of pigs per pen (22, 25, 28 and 31 pigs in T1, T2, T3 and T4, respectively).
Blood samples were collected on the final day of each growth stage. The average
daily gain (ADG) decreased significantly with decreased space allowances at all
growth stages, except at stage 2. Average daily feed intake (ADFI) was not
significantly affected by space allowances at stages 1 to 4; however, at stage 5,
there was a linear effect of space allowance on ADFI. Thus, the feed conversion
ratio showed results similar to those for ADG. Serum cortisol concentrations,
indicating the level of stress response, increased as space allowances decreased.
The highest serum cortisol concentrations were observed in T3 at stages 2 to 5.
Serum tumor necrosis factor-alpha levels were significantly higher in association
with a small space allowance than with at large space allowance at stages 2, 4
and 5. Serum interleukin-1beta levels also increased in a significant linear
manner at every growth stage in pigs reared at a low space allowance, except at
stage 4 (P=0.068). This study found that limited space allowance decreases the
growth performance of pigs and induces stress and inflammatory responses. We
confirmed that no significant effect of space allowance on growth performance and
serum cortisol concentrations are observed between T1 and T2 across all growth
stages. We suggest that the optimal space allowances for pigs according to their
BW are as follows: 0.24, 0.44, 0.64, 0.78 and 0.80 m2/pig for BWs of 11 to 25, 25
to 45, 45 to 65, 65 to 85 and 85 to 115 kg, respectively.
PMID- 27609542
TI - A Kirigami Approach to Forming a Synthetic Buckliball.
AB - The shape transformation of some biological systems inspires scientists to create
sophisticated structures at the nano- and macro- scales. However, to be useful in
engineering, the mechanics of governing such a spontaneous, parallel and large
deformation must be well understood. In this study, a kirigami approach is used
to fold a bilayer planar sheet featuring a specific pattern into a buckliball
under a certain thermal stimulus. Importantly, this prescribed spherical object
can retract into a much smaller sphere due to constructive buckling caused by
radially inward displacement. By minimizing the potential strain energy, we
obtain a critical temperature, below which the patterned sheet exhibits identical
principal curvatures everywhere in the self-folding procedure and above which
buckling occurs. The applicability of the theoretical analysis to the self
folding of sheets with a diversity of patterns is verified by the finite element
method.
PMID- 27609543
TI - Validation of a total IC50 method which enables in vitro assessment of
transporter inhibition under semi-physiological conditions.
AB - 1. Accurate predictions of clinical transporter-mediated drug-drug interactions
(DDI) from in vitro data can be challenging when compounds have poor solubility
and/or high nonspecific binding. Additionally, current DDI predictions for
compounds with high plasma-protein binding assume that the unbound fraction in
plasma is 0.01, if the experimental value is less than 0.01 or cannot be
determined. This approach may result in an overestimation of DDI risk. To
overcome these challenges, it may be beneficial to conduct inhibition studies
under physiologically relevant conditions. 2. Here, IC50 values, determined in
the presence of 4% bovine serum albumin approximating human plasma albumin
concentrations, were successfully used to predict DDI for uptake transporters,
OATP1B1/1B3, OCT1/2, OAT1/3 and MATE1/2K. 3. The IC50 values of reference
inhibitors with 4% bovine serum albumin, considered total IC50, were comparable
to the predicted values based on nominal IC50 values determined under protein
free conditions and unbound fraction in plasma. Calculation of R-total and
Cmax/IC50,total values using total plasma exposure and total IC50 values
explained the clinical DDI or absence of it for these inhibitors. 4. These
results suggest that IC50 determinations in the presence of 4% albumin can be
used, in the context of clinical total exposure, to predict DDI involving uptake
transporters.
PMID- 27609544
TI - The Configuration of Copolymer Ligands on Nanoparticles Affects Adhesion and
Uptake.
AB - Nanoparticles (NPs) are promising carriers for targeted drug delivery,
photodynamic therapy, and imaging probes. A fundamental understanding of the
dynamics of polymeric NP targeting to bilayer membranes is important to enhance
the design of NPs for higher adhesion, binding percentage, and efficiency. In
this study, dissipative particle dynamics simulations are applied to investigate
the adhesion and uptake processes of the rod, spherical, and striped NPs to cell
membranes. It is observed that the striped ligands can prevent NPs from rotating
even in active rotation. We further optimize striped NP to a more stabilized
structure. Uptake processes of NPs with different configurations are thoroughly
investigated in our simulations and among which Janus NP are indicated to improve
the penetration rate to 100%. These findings provide better insight into
patterned NP design and may help fabricate new NPs for biomedical applications.
PMID- 27609545
TI - Legacy in palliative care: Legacy that is lived.
PMID- 27609547
TI - A case report of a cochlear implant infection - A reason to explant the device?
AB - CLINICAL PRESENTATION: Case history of a paediatric patient with a cochlear
implant and a surgical site infection that developed as a result of acute otitis
media is presented. INTERVENTION: After conservative management including wound
debridement it was decided to explant a functioning device. OBJECTIVE AND
IMPORTANCE: In a number of cases, it is necessary to remove the infected albeit
functioning device, especially in the event of formation of the biofilm has
occurred. It is necessary to review and evaluate the methods with which these
major complications are routinely managed with the aim to increase the survival
ratio for the implanted device.
PMID- 27609546
TI - Application of optically-induced-dielectrophoresis in microfluidic system for
purification of circulating tumour cells for gene expression analysis- Cancer
cell line model.
AB - Circulating tumour cells (CTCs) in a blood circulation system are associated with
cancer metastasis. The analysis of the drug-resistance gene expression of cancer
patients' CTCs holds promise for selecting a more effective therapeutic regimen
for an individual patient. However, the current CTC isolation schemes might not
be able to harvest CTCs with sufficiently high purity for such applications. To
address this issue, this study proposed to integrate the techniques of optically
induced dielectrophoretic (ODEP) force-based cell manipulation and fluorescent
microscopic imaging in a microfluidic system to further purify CTCs after the
conventional CTC isolation methods. In this study, the microfluidic system was
developed, and its optimal operating conditions and performance for CTC isolation
were evaluated. The results revealed that the presented system was able to
isolate CTCs with cell purity as high as 100%, beyond what is possible using the
previously existing techniques. In the analysis of CTC gene expression,
therefore, this method could exclude the interference of leukocytes in a cell
sample and accordingly contribute to higher analytical sensitivity, as
demonstrated in this study. Overall, this study has presented an ODEP-based
microfluidic system capable of simply and effectively isolating a specific cell
species from a cell mixture.
PMID- 27609548
TI - Predictors of health-related quality of life in adult cochlear implant recipients
in South Africa.
AB - OBJECTIVE: To identify and describe predictors of health-related quality of life
(HRQoL) outcomes for adult cochlear implant (CI) recipients in South Africa.
DESIGN: A retrospective study of adult CI recipients was conducted and cross
sectional HRQoL outcome data were added at the time of data collection, using the
Nijmegen Cochlear Implant Questionnaire (NCIQ). Twenty-two potential predictive
factors were identified from the retrospective dataset, including demographic,
hearing loss, CI and risk-related factors. Multiple regression analyses were
performed to identify predictor variables that influence HRQoL outcomes. STUDY
SAMPLE: The study sample included 100 adult CI recipients from four CI programs,
implanted for at least 12 months. RESULTS: History of no tinnitus prior to CI,
bilateral implantation and mainstream schooling were strongly predictive of
better overall HRQoL outcomes. Factors such as age, age at implant, gender, onset
of hearing loss, duration of CI use and presence of risk factors did not predict
HRQoL scores. CONCLUSION: A range of significant prognostic indicators were
identified for HRQoL outcomes in adult CI recipients. These predictors of HRQoL
outcomes can guide intervention services' informational counselling.
PMID- 27609549
TI - Adverse skin reactions following percutaneous bone conduction implant surgery
using the linear incision technique with and without subcutaneous tissue
reduction.
AB - CONCLUSIONS: Adverse skin reactions were equally distributed among age groups,
surgical technique, or presence of a retroauricular incision. Implant loss was
observed more frequently in children when compared to adults and elderly.
OBJECTIVE: A bone conduction (osseointegrated) implant can be used for
rehabilitation of patients with conductive hearing loss or single-sided deafness.
The surgical technique has been modified to minimize adverse skin reactions and
other complications. Two commonly used techniques are the linear incision
technique with subcutaneous tissue reduction and the technique without tissue
reduction. The primary aim is to compare the complication rate between the two
surgical techniques. METHODS: Retrospective study on all bone conduction implant
cases implanted between April 1990 and July 2014 at a tertiary referral center.
Skin reactions were graded by Holgers' scale (grade 0-1: 'normal', grade 2-3:
'adverse'). The worst follow-up available was reported. RESULTS: Of the 289 bone
conduction implants, 25 were implanted in children, 220 in adults, and 44 in
elderly. Implant loss occurred in 2.8% of all cases: 8.0% in children, 2.3% in
adults, and 2.3% in the elderly. Skin overgrowth was seen in 4.2%: 4% in
children, 4.8% in adults, and 3.5% in the elderly. No differences were observed
in the amount of adverse skin reactions (16.8% vs 14.7%) or skin overgrowth (4.6%
vs 2.9%) between the surgical techniques. There was no difference in adverse skin
reactions if the patient had a retroauricular incision (14.4% with vs 17.8%
without prior incision).
PMID- 27609550
TI - Rapid mortality transition of Pacific Islands in the 19th century.
AB - The depopulation of Pacific islands during the 16th to 19th centuries is a
striking example of historical mass mortality due to infectious disease. Pacific
Island populations have not been subject to such cataclysmic infectious disease
mortality since. Here we explore the processes which could have given rise to
this shift in infectious disease mortality patterns. We show, using mathematical
models, that the population dynamics exhibited by Pacific Island populations are
unlikely to be the result of Darwinian evolution. We propose that extreme
mortality during first-contact epidemics is a function of epidemiological
isolation, not a lack of previous selection. If, as pathogens become established
in populations, extreme mortality is rapidly suppressed by herd immunity, Pacific
Island population mortality patterns can be explained with no need to invoke
genetic change. We discuss the mechanisms by which this could occur, including
(i) a link between the proportion of the population transmitting infectious
agents and case-fatality rates, and (ii) the course of infection with pathogens
such as measles and smallpox being more severe in adults than in children.
Overall, we consider the present-day risk of mass mortality from newly emerging
infectious diseases is unlikely to be greater on Pacific islands than in other
geographical areas.
PMID- 27609551
TI - Late atypical atrial flutter after ablation of atrial fibrillation.
AB - Cardiac surgery for structural heart disease (often involving the left atrium)
and radiofrequency catheter ablation of atrial fibrillation have led to an
increased incidence of regular atrial tachycardias, often presenting as atypical
flutters. This type of flutter is particularly common after pulmonary vein
isolation, especially after extensive atrial ablation including linear lesions
and/or defragmentation. The authors describe the case of a 51-year-old man, with
no relevant medical history, referred for a cardiology consultation in 2009 for
paroxysmal atrial fibrillation. After failure of antiarrhythmic therapy, he
underwent catheter ablation, with criteria of acute success. Three years later he
again suffered palpitations and atypical atrial flutter was documented. The
electrophysiology study confirmed the diagnosis of atypical left flutter and
reappearance of electrical activity in the right inferior pulmonary vein. This
vein was again ablated successfully and there has been no arrhythmia recurrence
to date. In an era of frequent catheter ablation it is essential to understand
the mechanism of this arrhythmia and to recognize such atypical flutters.
PMID- 27609552
TI - Epicardial fat tissue thickness is increased in patients with lichen planus and
is linked to inflammation and dyslipidemia.
AB - BACKGROUND AND OBJECTIVES: Lichen planus (LP) is a mucocutaneous inflammatory
disease. Inflammation plays a major role in the progression of atherosclerosis.
Epicardial fat tissue (EFT) has been shown to produce and secrete various
proatherogenic and proinflammatory hormones and cytokines. The aim of this study
was to assess EFT in patients with lichen planus. METHODS: Fifty-four patients
with LP and 50 controls were enrolled in the study. LP was diagnosed according to
the World Health Organization criteria. EFT was measured on the free wall of the
right ventricle in parasternal long-axis view, as previously described and
validated. RESULTS: There were positive correlations between EFT thickness and
platelet/lymphocyte ratio, neutrophil/lymphocyte ratio, duration of LP, and high
sensitivity C-reactive protein (hsCRP) (p<0.001, p<0.001, p=0.002 and p<0.001,
respectively). In multivariate analysis, after adjustments for relevant
confounders, LDL cholesterol, hsCRP, platelet/lymphocyte ratio and duration of LP
were independent predictors of EFT thickness in patients with LP (beta=0.231,
p=0.014; beta=0.205, p=0.037; beta=0.361, p=0.001 and beta=0.133, p=0.047,
respectively). CONCLUSION: EFT is increased in patients with LP compared to
control subjects. Duration of LP is correlated with EFT, and duration of LP is
also an independent predictor of increased EFT, which is a predictor of
subclinical atherosclerosis.
PMID- 27609553
TI - Right atrial deformation analysis in isolated left ventricular noncompaction -
insights from the three-dimensional speckle tracking echocardiographic MAGYAR
Path Study.
AB - OBJECTIVE: Isolated left ventricular noncompaction (ILVNC) is a rare
cardiomyopathy characterized by a prominent trabecular meshwork and deep
intertrabecular recesses. The present study aimed to examine right atrial (RA)
volumes, volume-based functional properties and strains by three-dimensional
speckle-tracking echocardiography (3DSTE) in ILVNC patients. METHODS: The study
group consisted of 13 patients with ILVNC (mean age: 54.6+/-14.1 years, six male)
and 23 healthy age- and gender-matched volunteers (mean age: 50.4+/-12.4 years,
10 male), who served as normal controls. Complete two-dimensional Doppler
echocardiography and 3DSTE were performed in all cases. RESULTS: Increased
systolic maximum (58.2+/-15.3 ml vs. 40.5+/-11.8 ml, p=0.0004) and diastolic pre
atrial contraction (39.6+/-16.1 ml vs. 28.2+/-9.2 ml, p=0.01) and minimum (46.2+/
17.5 ml vs. 34.6+/-11.6 ml, p=0.02) RA volumes were detected in ILVNC patients.
Only total (18.6+/-8.5 ml vs. 12.2+/-5.9 ml, p=0.01) and passive (12.0+/-13.3 vs.
5.9+/-3.7 ml, p=0.05) RA stroke volumes, representing features of RA reservoir
and conduit phases, were increased in ILVNC; active RA stroke volume and all
emptying fractions did not differ between ILVNC patients and matched controls.
Moreover, global, mean segmental and regional peak strains and strains at atrial
contraction showed no differences between ILVNC patients and controls.
CONCLUSIONS: 3DSTE-derived volumetric analysis confirmed increased cyclic RA
volumes in ILVNC. Only mild RA functional alterations were demonstrated in ILVNC.
PMID- 27609554
TI - Complex left main coronary stent restenosis treated through radial approach using
a sheathless catheter.
AB - A 64-year-old woman was admitted for non-ST elevation myocardial infarction. The
coronary angiogram showed a severe stenosis in the left anterior descending
artery (LAD) ostium. A 3.5 mm*18 mm everolimus-eluting stent was directly
deployed in the left main and proximal LAD, with significant jailing of the
circumflex (Cx) ostium. A 3.25 mm*11 mm everolimus-eluting stent was therefore
deployed in the Cx using the T-stenting and small protrusion technique. One year
later, the patient was readmitted for non-ST elevation myocardial infarction, and
the coronary angiogram showed ostial restenosis of the Cx stent. Optical
coherence tomography imaging confirmed the severity of ostial restenosis.
Percutaneous coronary intervention by a radial approach was performed using a
sheathless guide catheter.
PMID- 27609555
TI - Molecular and phenotypic characterization of Colletotrichum species associated
with anthracnose disease in peppers from Sichuan Province, China.
AB - The anthracnose caused by Colletotrichum species is an important disease that
primarily causes fruit rot in pepper. Eighty-eight strains representing seven
species of Colletotrichum were obtained from rotten pepper fruits in Sichuan
Province, China, and characterized according to morphology and the glyceraldehyde
3-phosphate dehydrogenase (GAPDH) sequence. Fifty-two strains were chosen for
identification by phylogenetic analyses of multi-locus sequences, including the
nuclear ribosomal internal transcribed spacer (ITS) region and the beta-tubulin
(TUB2), actin (ACT), calmodulin (CAL) and GAPDH genes. Based on the combined
datasets, the 88 strains were identified as Colletotrichum gloeosporioides, C.
siamense, C. fructicola, C. truncatum, C. scovillei, and C. brevisporum, and one
new species was detected, described as Colletotrichum sichuanensis. Notably, C.
siamense and C. scovillei were recorded for the first time as the causes of
anthracnose in peppers in China. In addition, with the exception of C. truncatum,
this is the first report of all of the other Colletotrichum species studied in
pepper from Sichuan. The fungal species were all non-host-specific, as the
isolates were able to infect not only Capsicum spp. but also Pyrus pyrifolia in
pathogenicity tests. These findings suggest that the fungal species associated
with anthracnose in pepper may inoculate other hosts as initial inoculum.
PMID- 27609556
TI - Functional adaptation of crustacean exoskeletal elements through structural and
compositional diversity: a combined experimental and theoretical study.
AB - The crustacean cuticle is a composite material that covers the whole animal and
forms the continuous exoskeleton. Nano-fibers composed of chitin and protein
molecules form most of the organic matrix of the cuticle that, at the macroscale,
is organized in up to eight hierarchical levels. At least two of them, the exo-
and endocuticle, contain a mineral phase of mainly Mg-calcite, amorphous calcium
carbonate and phosphate. The high number of hierarchical levels and the
compositional diversity provide a high degree of freedom for varying the
physical, in particular mechanical, properties of the material. This makes the
cuticle a versatile material ideally suited to form a variety of skeletal
elements that are adapted to different functions and the eco-physiological
strains of individual species. This review presents our recent analytical,
experimental and theoretical studies on the cuticle, summarising at which
hierarchical levels structure and composition are modified to achieve the
required physical properties. We describe our multi-scale hierarchical modeling
approach based on the results from these studies, aiming at systematically
predicting the structure-composition-property relations of cuticle composites
from the molecular level to the macro-scale. This modeling approach provides a
tool to facilitate the development of optimized biomimetic materials within a
knowledge-based design approach.
PMID- 27609557
TI - Farm production, market access and dietary diversity in Malawi.
AB - OBJECTIVE: The association between farm production diversity and dietary
diversity in rural smallholder households was recently analysed. Most existing
studies build on household-level dietary diversity indicators calculated from 7d
food consumption recalls. Herein, this association is revisited with individual
level 24 h recall data. The robustness of the results is tested by comparing
household- and individual-level estimates. The role of other factors that may
influence dietary diversity, such as market access and agricultural technology,
is also analysed. DESIGN: A survey of smallholder farm households was carried out
in Malawi in 2014. Dietary diversity scores are calculated from 24 h recall data.
Production diversity scores are calculated from farm production data covering a
period of 12 months. Individual- and household-level regression models are
developed and estimated. SETTING: Data were collected in sixteen districts of
central and southern Malawi. SUBJECTS: Smallholder farm households (n 408), young
children (n 519) and mothers (n 408). RESULTS: Farm production diversity is
positively associated with dietary diversity. However, the estimated effects are
small. Access to markets for buying food and selling farm produce and use of
chemical fertilizers are shown to be more important for dietary diversity than
diverse farm production. Results with household- and individual-level dietary
data are very similar. CONCLUSIONS: Further increasing production diversity may
not be the most effective strategy to improve diets in smallholder farm
households. Improving access to markets, productivity-enhancing inputs and
technologies seems to be more promising.
PMID- 27609558
TI - A study of nano-biosensors and their output amplitude analysis algorithms.
AB - The aim of this paper is to discuss the latest nano-biosensor technologies and
existing signal analyser algorithm methods so that an automatic and portable nano
biosensor analyser can be realised. In this paper, the latest nano-biosensors are
reviewed, and particular attention is given to sensors that provide amplitude
changes at their output. To provide an automatic signal analysis of these
changes, existing signal processing algorithms for peak detection are also
discussed in detail.
PMID- 27609559
TI - Re: Family History and Probability of Prostate Cancer, Differentiated by Risk
Category - A Nationwide Population-based Study.
PMID- 27609560
TI - Facile fabrication of electrolyte-gated single-crystalline cuprous oxide nanowire
field-effect transistors.
AB - Oxide semiconductors are considered to be one of the forefront candidates for the
new generation, high-performance electronics. However, one of the major
limitations for oxide electronics is the scarcity of an equally good hole
conducting semiconductor, which can provide identical performance for the p-type
metal oxide semiconductor field-effect transistors as compared to their electron
conducting counterparts. In this quest, here we present a bulk synthesis method
for single crystalline cuprous oxide (Cu2O) nanowires, their chemical and
morphological characterization and suitability as active channel material in
electrolyte-gated, low-power, field-effect transistors (FETs) for portable and
flexible logic circuits. The bulk synthesis method used in the present study
includes two steps: namely hydrothermal synthesis of the nanowires and the
removal of the surface organic contaminants. The surface treated nanowires are
then dispersed on a receiver substrate where the passive electrodes are
structured, followed by printing of a composite solid polymer electrolyte (CSPE),
chosen as the gate insulator. The characteristic electrical properties of
individual nanowire FETs are found to be quite interesting including accumulation
mode operation and field-effect mobility of 0.15 cm(2) V(-1) s(-1).
PMID- 27609561
TI - Different characteristics of cryptococcal meningitis between HIV-infected and HIV
uninfected patients in the Southwest of China.
AB - Cryptococcus is the major pathogen that causes fungal meningitis. In the People's
Republic of China, especially in the Southwest area, cryptococcal meningitis (CM)
in HIV-uninfected patients is more common than in HIV-infected patients. We
compared clinical features and laboratory data pertaining to CM in patients with
different immunological statuses. Demographic data, clinical manifestations, and
laboratory data from inpatients in West China Hospital Sichuan University were
collected from June 2009 to June 2014. Patients were grouped according to HIV
status. Continuous variables were evaluated by Student t-test or Wilcoxon rank
sum tests. Categorical variables were analyzed by chi2 test. Among 85 patients
with CM were identified, 53 (62.4%) were HIV-uninfected patients. CM occurred
more frequently in males in the HIV-infected group. Compared with HIV-infected
patients, HIV-uninfected patients had more leukocytes in their blood and more
leukocytes and protein in cerebrospinal fluid. More HIV-uninfected patients had
increased cerebrospinal fluid (CSF)/serum albumin ratios, while intrathecal
immunoglobulin G (IgG) synthesis was significantly increased. The rate of in
hospital mortality of HIV-infected CM patients was higher. Clinical signs are
similar between HIV-uninfected and HIV-infected CM patients. Fewer leukocytes and
protein was detected in the CSF and lower local synthesis of IgG in the central
nervous system in HIV-infected patients, which reflects their diminished immune
response. These characteristics should be noted in order to avoid misdiagnosis.
Meningeal enhancement and intrathecal IgG synthesis in the HIV-uninfected group
was significantly higher, that may be performance of aggressive inflammatory
response and might contribute to a better outcome.
PMID- 27609562
TI - 30 years of battling the cell wall.
AB - In Aspergillus fumigatus, like in other pathogenic fungi, the cell wall is
essential for fungal growth as well as for resisting environmental stresses such
as phagocytic killing. Most of the chemical analyses undertaken on the cell wall
of A. fumigatus are focused on the mycelial cell wall because it is the
vegetative stage of the fungus. However, the cell walls of the mycelium and
conidium (which is the infective propagule) are different especially at the level
of the surface layer, which plays a significant role in the interaction between
A. fumigatus conidia and phagocytic cells of the immune system. In spite of the
essential function of the cell wall in fungal life, progresses have been
extremely slow in the understanding of biosynthesis as well in the identification
of the key host responses against the cell wall components. A major difficulty is
the fact that the composition and structural organization of the cell wall is not
immutably set and is constantly reshuffled depending on the environmental
conditions.
PMID- 27609564
TI - Toxicology and the reproducibility crisis: Scientific publishing, hazard
assessment and risk characterization.
PMID- 27609563
TI - Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and
treatment of 31 reported cases.
AB - Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is
known about its epidemiology, clinical manifestations, laboratory features,
treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the
English literature from 1967 through 2015 for variables of arthritis with
Aspergillus spp. recovered from joint and/or adjacent bone, underlying
conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging,
management, and outcome. Among 31 evaluable cases, 87% were males and 13%
pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were
immunosuppressed with such conditions as hematological malignancies (26%),
corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%)
of patients had hematogenous seeding of the joint, and more than 80% had de novo
infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints)
occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical
manifestations included pain (87%), edema (26%), and limited function (23%), with
knees (35%), intervertebral discs (26%), and hips (16%) being most commonly
infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus
flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was
90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/MUL
(7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft
tissue extension 47%. Nineteen patients (61%) were managed with combined medical
and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery
only. Amphotericin B and itraconazole were the most frequently used agents with
median duration of therapy of 219 days (range 30-545). Surgical interventions
included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial
response was achieved in 71% and relapse occurred in 16%. Medical therapy was
reinstituted with successful outcome in these patients. Overall survival was 65%.
Aspergillus arthritis mainly develops as a de novo infection involving knees and
intervertebral disks in immunocompromised patients with localizing symptoms.
Contiguous osteomyelitis is frequently observed. Diagnosis is established by
synovial fluid culture. Aspergillus arthritis is therapeutically challenging with
most patients undergoing surgery and protracted antifungal therapy.
PMID- 27609566
TI - [Lipopolysaccharide promotes the proliferation of CD4(+) T cells by modulating
the survive and cytokine secretion of dendritic cells].
AB - Objective To explore the mechanism modulating the function of dendritic cells
(DCs) and promoting the T cell response by lipopolysaccharide (LPS). Methods
Splenic DCs were purified with anti-CD11c immunomagnetic beads. After DCs were
stimulated with LPS, the expressions of co-stimulatory molecules CD80 and CD86 on
the DCs were detected by flow cytometry. The protein levels of pro-inflammatory
cytokines interleukin 4 (IL-4), IL-5, IL-6, IL-12p40, IL-12p70 and tumor necrosis
factor alpha (TNF-alpha) in the culture supernatant were measured by ELISA. The
apoptotic levels of DCs which were labeled with annexinV-FITC/PI were determined
by flow cytometry. The phosphorylation level of nuclear factor kappaB P65 (NF
kappaB P65) was assessed by phos-flow. The mRNA levels of variable genes in
microarray were determined by real-time PCR. The proliferation of CD4(+) T cells
which were co-cultured with OVA323-329-treated DCs was analyzed by flow
cytometry. Results The purity of DCs reached over 93% after isolation. LPS up
regulated the expressions of CD80 and CD86 and enhanced DCs-mediated
proliferation of CD4(+) T cells. In addition, LPS increased the protein levels of
IL-12p40, TNF-alpha and IL-6, and inhibited the apoptosis of DCs through the NF
kappaB signaling pathway. Conclusion LPS could enhance DC-mediated proliferation
of CD4(+) T cells by modulating the DCs survival and cytokine secretion.
PMID- 27609565
TI - FtsZ does not initiate membrane constriction at the onset of division.
AB - The source of constriction required for division of a bacterial cell remains
enigmatic. FtsZ is widely believed to be a key player, because in vitro
experiments indicate that it can deform liposomes when membrane tethered. However
in vivo evidence for such a role has remained elusive as it has been challenging
to distinguish the contribution of FtsZ from that of peptidoglycan-ingrowth. To
differentiate between these two possibilities we studied the early stages of
division in Escherichia coli, when FtsZ is present at the division site but
peptidoglycan synthesizing enzymes such as FtsI and FtsN are not. Our approach
was to use correlative cryo-fluorescence and cryo-electron microscopy (cryo-CLEM)
to monitor the localization of fluorescently labeled FtsZ, FtsI or FtsN
correlated with the septal ultra-structural geometry in the same cell. We noted
that the presence of FtsZ at the division septum is not sufficient to deform
membranes. This observation suggests that, although FtsZ can provide a
constrictive force, the force is not substantial at the onset of division.
Conversely, the presence of FtsN always correlated with membrane invagination,
indicating that allosteric activation of peptidoglycan ingrowth is the trigger
for constriction of the cell envelope during cell division in E. coli.
PMID- 27609567
TI - [Administration of bone marrow mesenchymal stem cells attenuates inflammation of
rats with sepsis].
AB - Objective To investigate the therapeutic effects of bone marrow-derived
mesenchymal stem cells (BMSCs) in rats with sepsis. Methods Forty-eight Wistar
rats were divided into blank group, sham group, model group and treatment group.
Sepsis model was made using cecum ligation and puncture (CLP). BMSCs were
extracted and cultured to the third generation. The rats in the treatment group
received BMSCs through a tail vein and the rats in the model group received an
equivalent dose of PBS. The survival rate was recorded in each group 72 hours
after operation. Pathological changes of lung tissues were observed by HE
staining. The mRNA levels of interleukin 6 (IL-6), tumor necrosis factor alpha
(TNF-alpha), fork head box protein 3 (Foxp3), CC chemokine ligand 2 (CCL2) were
tested by quantitative real-time fluorescence PCR. The serum levels of IL-6, IL
17 and TNF-alpha proteins were detected by ELISA. Results In both blank group and
sham group, the survival rate and histological changes of the lungs showed
normal; no bacteria were found growing in rats' blood culture; IL-6, IL-17, TNF
alpha, CCL2, Foxp3 mRNA and IL-6, IL-17, TNF-alpha protein levels had no
significant differences. In the model group, the survival rate of rats was
obviously lower than that of the sham group; the pathological changes of the
lungs were significant; any amount of enterobacteria were seen growing in rats'
blood culture; IL-6, IL-17, TNF-alpha, CCL2 mRNA and protein expression levels
were apparently higher than those of sham group, while Foxp3 mRNA expression
level was obviously lower than that of sham group. In the treatment group, the
survival rate was significantly higher than that of the model group; the
pathological changes of the lung tissues were evidently eased; IL-6, IL-17, TNF
alpha, CCL2 mRNA and protein expression levels significantly decreased compared
with the model group, while Foxp3 mRNA expression level significantly increased
compared with the model group. Conclusion BMSCs injection increases the survival
rate in rats with sepsis and reduces the levels of inflammatory cytokines.
PMID- 27609568
TI - [Regulatory B cells activated by CpG-ODN combined with anti-CD40 monoclonal
antibody inhibit CD4(+)T cell proliferation].
AB - Objective To observe the immunosuppressive function of regulatory B cells (Bregs)
in vitro after activated by CpG oligodeoxynucleotide (CpG-ODN) and anti-CD40 mAb.
Methods Mice splenic CD5(+)CD1d(high)B cells and CD5(-)CD1d(low)B cells were
sorted by flow cytometry. These B cells were first stimulated with CpG-ODN
combined with anti-CD40 mAb for 24 hours, and then co-cultured with purified
CD4(+)T cells. The interleukin 10 (IL-10) expression in the activated Bregs and
other B cell subset, as well as the proliferation and interferon gamma (IFN
gamma) expression in the CD4(+) T cells activated by anti-CD3 mAb plus anti-CD28
mAb were determined by flow cytometry. Results CD5(+)CD1d(high) B cells activated
by CpG-ODN plus anti-CD40 mAb blocked the up-regulated CD4(+)T proliferation and
significantly reduced the IFN-gamma level. At the same time, activated CD5(
)CD1d(low)B cells showed no inhibitory effect on CD4(+)T cells. Further study
revealed that IL-10 expression in the CD5(+)CD1d(high) B cells were much higher
than that in the CD5(-)CD1d(low)B cells after stimulated with CpG-ODN combined
with anti-CD40 mAb for 24 hours. Conclusion CD5(+)CD1d(high) B cells activated by
CpG-ODN combined with anti-CD40 mAb have immune inhibitory effects on CD4(+)T
cell activation in vitro , which possibly due to IL-10 secretion.
PMID- 27609569
TI - [Elevated expression of B7-H6 in U87 cells-derived glioma stem like cells is
associated with biological characteristics].
AB - Objective To investigate the expression and biological significance of
costimulatory molecule B7-H6, a member of B7 family, in glioma stem like cells
(GSLCs). Methods In virtue of the ability of forming neurospheres in vitro ,
GSLCs were isolated from U87 cells by cell sub-cloning. Real-time quantitative
PCR and flow cytometry were performed to detect the expressions of stem cell
related markers (c-myc, Sox2, CD133, nestin, and CXCR4), as well as the
expressions of B7 family molecules. The different doses of adriamycin,
carboplatin, cisplatin, were used to treat GSLCs for testing their chemotherapy
resistance. After the expression of B7-H6 in GSLCs was knockdown by siRNA, CCK-8
method was used to detect cell proliferation. Results GSLCs were successfully
isolated from U87 cells, which formed neurospheres in vitro . The expressions of
multiple stem cell markers were up-regulated and the GSLCs showed enhanced chemo
therapy-resistance. B7 family members, B7-H1, B7-H3, B7-H4 and B7-H6 were
expressed in GSLCs. Compared with primary U87 cells, GSLCs presented with a
remarkably increased expression of B7-H6 on cell membrane. When B7-H6 was
silenced by siRNA, cell proliferation was inhibited along with the decrease of c
myc expression. Conclusion The expression of B7-H6 is up-regulated in U87-derived
GSLCs, which is associated with the biological characteristics of GSLCs.
PMID- 27609570
TI - [Macrophages promote the migration of neural stem cells into mouse spinal cord
injury site].
AB - Objective To explore the role of macrophages in the migration of neural stem
cells (NSCs) in vivo and in vitro . Methods NSCs with green fluorescent protein
(GFP) were isolated from GFP transgenic mice and the immunofluorescence
cytochemical staining of nestin was used to identify NSCs. After spinal cord
injury was induced, the tissue level of macrophage chemotactic protein-1 (MCP-1)
mRNA was detected using quantitative real time PCR. The migration of GFP-NSCs was
investigated 1 week after GFP-NSCs were injected into both sides of the damaged
area. The effect of macrophage on the migration of NSCs in vitro was tested by
Transwell(TM) system and the content of MCP-1 was detected by ELISA. Results NSCs
highly expressed nestin. Compared with the control group, the level of MCP-1 mRNA
significantly increased in the spinal cord injury group. The NSCs which were
injected into the spinal cord migrated into the center of the injured site where
F4/80 was highly expressed. Macrophages significantly increased the number of
migrating NSCs in vitro and the secretion of MCP-1. Conclusion Macrophages induce
NSC migrating into the spinal cord injury site possibly through promoting the
secretion of MCP-1.
PMID- 27609571
TI - [SapM-induced fusion blocking of autophagosome-lysosome is depended on
interaction with Rab7].
AB - Objective To study the role of Rab7 in the blockage of autophagosome-lysosome
fusion induced by secretory acid phosphatase (SapM), a virulence factor of
mycobacterium tuberculosis. Methods The Raw264.7 cells were transfected with
siRab7, and the P62 was detected using Western blotting. After transfected with
mCherry-SapM, the co-localization of SapM and Rab7 in Raw264.7 cells was detected
by immunofluorescence cytochemistry and the interaction of SapM with Rab7 was
determined by co-immunoprecipitation. SapM mutants including SapM(delta ARCA),
SapM(delta FRED) and SapM(delta CT) were used to transfect Raw264.7 cells, and
their associations with Rab7 were analyzed. Results The treatment of siRab7
induced a significant increase of P62 in these cells. Immunofluorescence
cytochemistry showed the intracellular co-localization of SapM and Rab7. Co
immunoprecipitation showed that SapM and Rab7 were precipitated by each other.
Only SapM(delta CT) failed to interact with Rab7 among the three SapM mutants.
Conclusion The inhibition of autophagosome-lysosome fusion induced by SapM is
dependent on the interaction between SapM and Rab7.
PMID- 27609572
TI - [Overexpression of KIAA1456 inhibits the proliferation of HO8910PM cells].
AB - Objective To investigate the effect of over-expressed KIAA1456 on the
proliferation and cell cycle of HO8910PM cells. Methods KIAA1456 was amplified by
PCR and inserted into lentiviral expression vector Ubi-MCS-EGFP-IRES-puromycin to
construct Ubi-KIAA1456-EGFP-puromycin (LV-KIAA1456) vector. Thereafter, the
lentiviral particles were packaged and used to infect HO8910PM cells. The green
fluorescence protein (GFP) expression was observed at 72 hours. The expression of
KIAA1456 was examined by reverse transcription PCR and Western blotting. Cell
growth was detected with CCK-8 assay and cell cycles were analyzed by flow
cytometry. Results Reverse transcription PCR and Western blotting showed that
HO8910PM cells infected with LV-KIAA1456 vector over-expressed KIAA1456 mRNA and
protein. Cell proliferation was inhibited and G1 phase cells significantly
increased in HO8910PM cells overexpressing KIAA1456. Conclusion Over-expression
of KIAA1456 inhibits the proliferation of HO8910PM ovarian cancer cells and
arrests the cell cycle in G1 phase.
PMID- 27609573
TI - [Envelope protein of Jaagsiekte sheep retrovious expressed in NIH3T3 cells
promotes cell proliferation].
AB - Objective To explore the influence of the exogenous Jaagsiekte sheep retrovious
(exJSRV) envelope protein (Env) on NIH3T3 cell proliferation. Methods A
recombinant plasmid pcDNA4/myc-His/exJSRV- env carrying exJSRV- env gene was
constructed, and then the correctness of the recombinant plasmid was identified
by PCR, restriction enzyme digestion and sequencing. The recombinant plasmid
pcDNA4/myc-His/exJSRV- env was transiently transfected into NIH3T3 cells by
Lipofectamine(TM) LTX. After the transfection of the recombinant plasmid, the
expression of exJSRV- env was detected by reverse transcription PCR and Western
blotting. The effect of Env on cell proliferation was investigated by CCK-8 assay
and plate colony formation assay. Results The recombinant eukaryotic expression
plasmid containing exJSRV- env was successfully constructed as identified by PCR,
restriction enzyme identification and sequencing. After the recombinant plasmid
was transiently transfected into NIH3T3 cells, reverse transcription PCR and
Western blotting showed the expression of exJSRV- env , and Env promoted NIH3T3
cell proliferation significantly. Conclusion JSRV Env was expressed successfully
in the NIH3T3 cells and promoted the proliferation of NIH3T3 cells.
PMID- 27609574
TI - [High expression of snail in mouse cerebral cortex following kainic acid-induced
status epilepticus].
AB - Objective To observe the expression of snail in mouse cortex in the model of
status epilepticus (SE) induced by kainic acid (KA) and explore the role of snail
in SE. Methods Sixty-four adult male C57/BL6 mice were randomly divided into
control group and SE group, 32 mice in each group. Intraperitoneal injection of
normal saline was performed in control group; instead, KA was injected
intraperitoneally in SE group to induce SE. The organs were harvested 3, 8, 24
and 72 hours post the cessation of each group. Reverse transcription-PCR was used
to detect the expression of snail mRNA; the expression of snail protein was
tested by Western blotting; the distribution of snail was determined using
immunohistochemistry; snail expression in cortex was located by
immunofluorescence technique. Results Compared with the control group, mRNA and
protein expression of snail in SE group were significant higher, and they reached
the peak at 24 hours. Immunohistochemistry indicated weak positive expression of
snail in control group. In SE group, it was widely distributed in different
cortical neurons and glial cells. Immunofluorescence histochemistry further
proved that snail was localized in neurons and astrocytes. Conclusion Snail is
strongly expressed in neuron and astrocyte of mouse cortex at KA-induced SE,
which indicates snail is possibly related to the attack of SE.
PMID- 27609575
TI - [Dexmedetomidine suppresses the expressions of TLR4, NF-kappaB and ICAM-1 mRNA in
the lung of rabbits during one lung ventilation].
AB - Objective To investigate the effect of dexmedetomidine on lung injury and the
expressions of Toll-like receptor 4 (TLR4), nuclear factor kappaB p65 (NF-kappaB
p65) and intercellular adhesion molecular 1 (ICAM-1) mRNA during one-lung
ventilation (OLV) in rabbits. Methods Thirty healthy New Zealand white rabbits
were randomly divided into three groups ( n=10 in each group): two-lung
ventilation (TLV) group (group T), OLV group (group O), dexmedetomidine used
during OLV group (group D-O). The rabbits in group T were treated with TLV for
3.5 hours, while in group O and group D-O, the rabbits were ventilated through
right lung for 3 hours following 30-minute TLV. In group D-O, dexmedetomidine (1
MUg/kg) were given intravenously for 10 minutes before tracheostomy, followed by
intravenous infusion at the rate of 1 MUg/(kg.h). Equal volume of normal saline
was given in group O and group T as controls. At the end of the experiment,
rabbits were sacrificed and lung tissues were collected. The pulmonary wet/dry
mass (W/D) ratio was calculated and the pathological changes of the lungs were
observed using HE staining under a light microscope. The expressions of TLR4, NF
kappaB p65, ICAM-1 mRNA were analyzed by real-time quantitative PCR. Results W/D
ratio of left lung tissues in group O and group D-O were significantly higher as
compared with group T. However, W/D ratio in group D-O was obviously lower than
that in group O. Compared with group T, both group O and group D-O showed much
more serious morphological damage in the lung, and such lung injury was less
obvious in group D-O than in group O. The expressions of TLR4, NF-kappaB p65,
ICAM-1 mRNA increased significantly in group O as compared with group T, and such
enhancement was ameliorated by dexmedetomidine as observed in group D-O.
Conclusion Dexmedetomidine might inhibit inflammatory responses and attenuate OLV
induced lung injury in rabbits, possibly by suppressing the expressions of TLR4
and NF-kappaB p65 mRNA.
PMID- 27609576
TI - [The miR-148a alleviates hepatic ischemia/reperfusion injury in mice via
targeting CaMKIIalpha].
AB - Objective To evaluate the impact of miR-148a on hepatic ischemia/reperfusion
(I/R) injury via inhibiting Ca(2+)/calmodulin-dependent protein kinase IIalpha
(CaMKIIalpha), and analyze the potential mechanism. Methods Liver I/R model was
built in mice. Expression of CaMKIIalpha was detected in the hepatic tissues by
Western blotting. The mRNA levels of miR-148a, CaMKIIalpha, tumor necrosis factor
alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were analyzed by quantitative
real-time PCR (qRT-PCR). HE staining was performed to observe morphological
changes of the livers in each group. TUNEL was used to evaluate the degree of
hepatocellular apoptosis in each group. Results After hepatic I/R injury, the
expression of miR-148a increased, and it was negatively correlated with
CaMKIIalpha. After therapy with exogenous miR-148a mimics, the protein expression
of CaMKIIalpha, the mRNA levels of TNF-alpha and IL-1beta, the degree of
inflammatory cell infiltration and liver cell necrosis, and the level of
hepatocellular apoptosis were all downregulated. Conclusion The miR-148a may
alleviate hepatic I/R injury in mouse by inhibiting CaMKIIalpha.
PMID- 27609577
TI - [Knockdown of Drosha promotes chemosensitivity of epirubicin for gastric cancer
MGC-803 cells].
AB - Objective To establish a gastric cancer cell line with stable Drosha silenced and
explore the effect of Drosha on the chemosensitivity of gastric cancer cells to
epirubicin. Methods Interfering sequences targeting Drosha were designed and
inserted into the lentiviral vectors, which were used to transfect MGC-803 cells.
The level of Drosha mRNA was detected by quantitative real-time PCR; Drosha
protein was detected by Western blotting; MTT assay was performed to test the 50%
inhibitory concentration (IC50) of epirubicin agaisnt wide-type MGC-803 cells.
After the treatment with IC50 epirubicin, the apoptosis rate of each cell group
was determined by flow cytometry; the expressions of apoptosis-related proteins
caspase-3, caspase-9, Bax, Bcl-2 were assessed by Western blotting. Results The
gastric cancer MGC-803 cells with stable Drosha silenced were successfully
established, and the levels of Drosha mRNA and protein were reduced. After the
cells were treated with 0.5 mg/L(IC50) epirubicin, the apoptosis rate of MGC-803
cells was raised, the protein expressions of caspase-3 , caspase-9 and Bax were
significantly upregulated and Bcl-2 was downregulated. Conclusion The silence of
Drosha expression can promote the sensitivity of gastric cancer to epirubicin.
PMID- 27609578
TI - [Activation of autophagy pathway in hippocampus and deterioration of learning and
memory ability by intermittent hypoxia in rats after cerebral ischemia].
AB - Objective To investigate the effects of different duration of intermittent
hypoxia on the autophagy pathway in the hippocampus and the learning and memory
ability after cerebral ischemia in rats. Methods 100 male Wistar rats were
randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R)
group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7
I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion
(IH14-I/R) group, intermittent hypoxia for 21 days combined with
ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R
group, IH14-I/R group and IH21-I/R group were respectively subjected to
intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved
Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells
in the hippocampus of rat brain were detected by HE staining; the levels of
mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were
determined by quantitative real-time PCR; the distribution of mTOR and beclin 1
in the hippocampus was observed by immunohistochemistry; the learning and memory
ability of rats was assessed by the Morris water maze test. Results Compared with
the SO group, the never cell morphology was damaged, the number of survival
neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in
the hippocampus were strengthened, and the learning and memory ability declined
in the I/R group. Compared with the I/R group, the never cell morphology was
damaged seriously, the number of survival neurons in the hippocampus decreased,
the expressions of mTOR and beclin 1 in the hippocampus increased, and the
learning and memory ability dropped in the intermittent hypoxia groups. What's
more, the above changes were dependent on the duration of intermittent hypoxia.
Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory
after cerebral ischemia and the damages increase with time passing, which are
related to mTOR-beclin 1 activation and increasing neuronal cell death.
PMID- 27609579
TI - [Knockdown of dachshund homolog 1 (DACH1) promotes cell apoptosis and inhibits
the invasion and migration abilities of Capan-1 pancreatic cancer cells].
AB - Objective To investigate the impact of the decreased expression of dachshund
homolog 1 (DACH1) on cell cycle, apoptosis, invasion and migration of Capan-1
pancreatic cancer cells. Methods After four pairs of DACH1 siRNA were designed
and synthesized, double-stranded short hairpin RNA (shRNA) were annealed and
inserted into pGenesil-1 vector. The product was then confirmed by enzyme
digestion and sequencing analysis. The recombinant plasmids were transfected into
Capan-1 cells via Lipofectamine(TM) 2000. Fluorescence microscopy, reverse
transcription PCR (RT-PCR) and Western blotting were used to detect the
transfection efficiency. Cell apoptosis and cell cycle were tested by flow
cytometry. Transwell(TM) assay was used to monitor the invasion and migration
abilities of Capan-1 cells. Results Recombinant plasmid pshRNA-DACH1 was
successfully constructed and transfected into Capan-1 cells. After transfection,
the expression of DACH1 was reduced to some extent. Flow cytometry revealed that
cell apoptosis was promoted in the pshRNA-DACH1 transfected group compared with
control groups, whereas cell cycle had no significant differences among the
groups. Transwell(TM) assay validated that the abilities of migration and
invasion were inhibited in the pshRNA-DACH1 transfected group. Conclusion
Knockdown of DACH1 expression can remarkably enhance the cell apoptosis, restrain
the proliferation, migration and invasion of Capan-1 cells.
PMID- 27609580
TI - [Activation of peripheral T lymphocytes in children with epilepsy and production
of cytokines].
AB - Objective To study the state of peripheral T lymphocytes and cytokine levels in
children with epilepsy. Methods Twenty children with epilepsy and 20 healthy age
matched children were recruited and their peripheral blood was collected. The
activation of T lymphocytes was evaluated by detecting the expressions of CD25,
CD69 and cytotoxic T lymphocyte-assicated antigen 4 (CTLA4). The function of T
lymphocytes was evaluated by detecting the expressions of interferon gamma (IFN
gamma), tumor necrosis factor alpha (TNF-alpha), IL-17A and IL-6. The activation
of regulatory T cells (Tregs) was evaluated by detecting the expression of IL-10.
Results Children with epilepsy had higher expressions of CD25, CD69 and CTLA-4 in
T lymphocytes than the controls did. The expressions of IFN-gamma, TNF-alpha, IL
17A and IL-6 in T lymphocytes of children with epilepsy were higher than those of
the controls. Frequency of Tregs producing IL-10 was higher in children with
epilepsy as compared with the controls. Conclusion Peripheral T lymphocytes of
children with epilepsy are activated and produce cytokines.
PMID- 27609581
TI - [The expression and significance of miR-33b and HMGA2 in esophageal squamous cell
carcinoma].
AB - Objective To investigate the expression and significance of miR-33b and high
mobility group AT-hook 2 (HMGA2) in esophageal squamous cell carcinoma (ESCC).
Methods Real-time quantitative PCR (qRT-PCR) was used to detect the expression
levels of miR-33b and HMGA2 mRNA from the ESCC and adjacent tissues.
Immunohistochemical SP method was performed to test the protein level of HMGA2.
After the miR-33b mimics, inhibitor and controls were separately transfected into
TE-1 and Eca-109 cells, the expression levels of miR-33b and HMGA2 in each group
were again determined by qRT-PCR and Western blotting. Results The expression
level of miR-33b from the ESCC tissues of 40 cases were significantly lower than
that from the adjacent normal tissues. However, the expression level of HMGA2
protein from the ESCC tissues were significantly higher than that from the
adjacent normal tissues. The expression level of miR-33b in the HMGA2 positive
group was lower than that in the HMGA2 negative group. The correlation analysis
showed that the expression of miR-33b was negatively correlated with the mRNA
expression of HMGA2 in the ESCC tissues. There were no significant difference in
the mRNA expression of HMGA2 among the cells transfected separately with miR-33b
mimics, inhibitor and controls, but Western blotting indicated that the protein
expression of HMGA2 decreased significantly in the miR-33b over-expressed cells.
Conclusion The expression of miR-33b decreases and HMGA2 increases in the ESCC
tissues. The over-expression of miR-33b could suppress the protein expression of
HMGA2 in the esophageal cancer cells, but the mRNA expression of HMGA2 would not
be affected, which suggests that miR-33b might regulate the protein expression of
HMGA2 in the post-transcriptional level.
PMID- 27609582
TI - [Increased expressions of programmed death 1 (PD-1) and its ligands in peripheral
CD3(+) T cells and CD19(+) B cells in patients with hepatocellular carcinoma].
AB - Objective To investigate the changes of programmed death 1 (PD-1) and ligands, as
well as interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells
(PBMCs) of patients with hepatocellular carcinoma (HCC). Methods The peripheral
blood was collected from 15 early HCC patients, 13 progressive HCC patients and
12 healthy volunteers. PBMCs was isolated from the peripheral blood. The
expressions of PD-1, PD-L1 and PD-L2 in PBMCs were detected by flow cytometry;
the serum level of IFN-gamma was determined by ELISA; the correlation of PD-1 and
IFN-gamma was analyzed with Pearson's correlation and One-way ANOVA. Results The
expression levels of PD-1, PD-L1 and PD-L2 in CD3(+) T cells and CD19(+) B cells
and serum IFN-gamma level in progressive HCC patients were significantly higher
than those in the healthy group and early HCC patients. The expression levels of
PD-1, PD-L1 and PD-L2 in the CD3(+) T cells and CD19(+) B cells of the HCC
patients were positively correlated with IFN-gamma. Conclusion The expression
levels of PD-1, PD-L1 and PD-L2 increase in the PBMCs of HCC patients; PD-1 and
PD-L1 are correlated with IFN-gamma level.
PMID- 27609583
TI - [Preparation and identification of monoclonal antibodies against chicken cell
cycle checkpoint kinase 2 (cChk2)].
AB - Objective To prepare monoclonal antibodies (mAbs) against chicken cell cycle
checkpoint kinase 2 (cChk2). Methods The cChk2 gene was amplified by reverse
transcription PCR (RT-PCR) and subcloned into the prokaryotic expression vector
pGEX-4T-3. After induced by IPTG, cChk2 was expressed in BL21 (DE3) E.coli cells
and analyzed by SDS-PAGE to determine its soluability. BALB/c mice were immunized
with cChk2 protein peritoneally. Indirect immunofluorescence assay (IFA) and
Western blotting were used to detect anti-serum; if the detection result was
positive, IFA and limited dilution was performed to screen hybridoma clones that
produced antibodies against cChk2. Results cChk2 was mainly expressed in
inclusion bodies. The anti-sera were able to recognize Chk2. Nine positive
hybridoma clones were obtained and identified as 1F4, 2D9, 2G1, 3D9, 3E3, 4B5,
4E2, 5C9 and 5F7. Conclusion The study has prepared mAbs against cChk2 with a
good specificity and a high titer.
PMID- 27609584
TI - [Construction of anti-B7-H4-scFv library and screening and identification of anti
B7-H4-scFv].
AB - Objective To construct the ribosome display library of anti-B7-H4 extracellular
domain, and select the antibody with high specificity. Methods The cDNA of B7-H4
extracellular domain was amplified from A549 cells by reverse transcription PCR
(RT-PCR). To express ectodomains of B7-H4, the sequence of B7-H4 gene, which
encodes the B7-H4 extracellular domains, was inserted into plasmid pET-28a(+).
The purified recombinant protein of B7-H4 extracellular domain was used to
immunize BALB/c mice. The total RNA was extracted from the spleen of BALB/c mice
which had been immunized with B7-H4 recombinant protein. The genes of VH, Vkappa
and VH/Vkappa were amplified separately by RT-PCR and splicing by overlap
extension PCR (SOE-PCR). The gene of VH/ Vkappa was ligated into pUM19-T vector
and the ligated sample was transformed into competent E.coli DH5alpha. The
resulting plasmid was isolated and then subjected to sequencing to verify the
gene sequence. TNT(R)T7 Quick for PCR DNA kit was used to translate and screen
the anti-B7-H4-scFv in vitro from the ribosome display library. Western blotting
and an indirect ELISA were performed to detect the specificity of anti-B7-H4
scFv. Results The right sequences of VH, Vkappa and VH/Vkappa were acquired,
which were 439, 680 and 1098 bp in length, respectively. The analysis of
specificity demonstrated that the anti-B7-H4-scFv screened from the ribosome
display library had a high specific combining ability with B7-H4. Conclusion The
experiment has successively constructed the ribosome display library of anti-B7
H4 extracellular domain, and selected the anti-B7-H4-scFv which has a high
specific binding ability with recombinant protein of B7-H4 extracelluar domain.
PMID- 27609585
TI - Paradoxical cold conditions during the medieval climate anomaly in the Western
Arctic.
AB - In the Northern Hemisphere, most mountain glaciers experienced their largest
extent in the last millennium during the Little Ice Age (1450 to 1850 CE, LIA), a
period marked by colder hemispheric temperatures than the Medieval Climate
Anomaly (950 to 1250 CE, MCA), a period which coincided with glacier retreat.
Here, we present a new moraine chronology based on (36)Cl surface exposure dating
from Lyngmarksbraeen glacier, West Greenland. Consistent with other glaciers in
the western Arctic, Lyngmarksbraeen glacier experienced several advances during
the last millennium, the first one at the end of the MCA, in ~1200 CE, was of
similar amplitude to two other advances during the LIA. In the absence of any
significant changes in accumulation records from South Greenland ice cores, we
attribute this expansion to multi-decadal summer cooling likely driven by
volcanic and/or solar forcing, and associated regional sea-ice feedbacks. Such
regional multi-decadal cold conditions at the end of the MCA are neither resolved
in temperature reconstructions from other parts of the Northern Hemisphere, nor
captured in last millennium climate simulations.
PMID- 27609586
TI - Conformational changes associated with L16P and T118M mutations in the membrane
embedded PMP22 protein, consequential in CMT-1A.
AB - Peripheral myelin protein 22 (PMP22) resides in the plasma membrane and is
required for myelin formation in the peripheral nervous system. Excess PMP22
mutants accumulate in the endoplasmic reticulum (ER) resulting in the inherited
neuropathies of Charcot-Marie-Tooth disease. However, there was no evidence of
the structure of PMP22 or how mutations affect its folding. Therefore, in this
study, we combined bioinformatics and homology modeling approaches to obtain
three-dimensional native and mutated PMP22 models and its anchoring to a POPC
membrane, submitted to .5-MUs MD simulations, to determine how the L16P and T118M
mutations affect the conformational behavior of PMP22. In addition, we
investigated the ability of the native and mutated species to accumulate in the
ER, via interaction with RER1, by combining protein-protein docking and MD
simulations, taking the conformations that were most representative of the native
and mutated PMP22 systems and RER1 conformations. Principal component analysis
over MD simulations revealed that L16P and T118M mutations resulted in increased
structural instability compared to the native form, which is consistent with
previous experimental findings of increased structural fluctuations along a loop
connecting transmembrane alpha-helix1 and alpha-helix2. Docking and MD
simulations coupled with the MMGBSA approach allowed the identification that the
binding interface for the PMP22-RER1 complex takes place through transmembrane
alpha-helix1 and alpha-helix2, with higher effective binding free energy values
between the mutated PMP22 systems and RER1 than for the native PMP22, mainly
through van der Waals interactions.
PMID- 27609588
TI - Unilateral pleural effusion in a peritoneal dialysis patient.
PMID- 27609589
TI - Mediastinal bronchogenic cyst mimicking congenital lobar emphysema.
AB - Bronchogenic cyst (BC) is a rare congenital malformation of the lung. Most
patients remain asymptomatic until adulthood while some are symptomatic in the
first few years of life. However, symptoms in newborn period are rare. We report
a case of a 3-day-old preterm baby with respiratory distress diagnosed as
congenital lobar emphysema on chest X-ray. A CT scan revealed a mediastinal cyst
causing obstructive lobar emphysema. The cyst was excised and pathological
examination was suggestive of BC.
PMID- 27609587
TI - Clinical aspects of symptomatic hyponatremia.
AB - Hyponatremia (HN) is a common condition, with a large number of etiologies and a
complicated treatment. Although chronic HN has been shown to be a predictor of
poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN
have not proven to increase life expectancy. For symptomatic HN, in contrast, the
necessity for urgent treatment has broadly been accepted to avoid the development
of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium
in chronic HN may result in cerebral damage due to osmotic demyelinisation.
Recently, administration of hypertonic saline bolus has been recommended as first
line treatment in patients with moderate-to-severe symptomatic HN. This approach
is easy to memorize and holds the potential to greatly facilitate the initial
treatment of symptomatic HN. First-line treatment of chronic HN is fluid
restriction and if ineffective treatment with tolvaptan or in some patients other
agents should be considered. A number of recommendations and guidelines have been
published on HN. In the present review, the management of patients with HN in
relation to everyday clinical practice is summarized with focus on the acute
management.
PMID- 27609590
TI - Aspirin unmasking acquired haemophilia A in a patient with prostate cancer.
AB - A 72-year-old man, on treatment for prostate cancer, attended the emergency
department with his 2nd episode of spontaneous extensive bruising and haematomas.
His first presentation was 2 months prior but this was thought to be because of
his aspirin and he improved when aspirin was discontinued. On this occasion
aspirin had been restarted 7 days before he developed his symptoms. His blood
investigation was significant for a much raised activated partial thromboplastin
time (aPTT). On his 3rd day of admission he deteriorated clinically with a
drastic drop in his haemoglobin and worsening tense haematomas. Blood
investigations confirmed the diagnosis of acquired factor VIII deficiency and he
subsequently received treatment with factor VIII inhibitor bypassing activity,
steroids and immunosuppresants.
PMID- 27609591
TI - Safe care can't be guaranteed if five day strikes go ahead, NHS boss warns.
PMID- 27609592
TI - Epigenetic studies in Developmental Origins of Health and Disease: pitfalls and
key considerations for study design and interpretation.
AB - The field of Developmental Origins of Health and Disease (DOHaD) seeks to
understand the relationships between early-life environmental exposures and long
term health and disease. Until recently, the molecular mechanisms underlying
these phenomena were poorly understood; however, epigenetics has been proposed to
bridge the gap between the environment and phenotype. Epigenetics involves the
study of heritable changes in gene expression, which occur without changes to the
underlying DNA sequence. Different types of epigenetic modifications include DNA
methylation, post-translational histone modifications and non-coding RNAs.
Increasingly, changes to the epigenome have been associated with early-life
exposures in both humans and animal models, offering both an explanation for how
the environment may programme long-term health, as well as molecular changes that
could be developed as biomarkers of exposure and/or future disease. As such,
epigenetic studies in DOHaD hold much promise; however, there are a number of
factors which should be considered when designing and interpreting such studies.
These include the impact of the genome on the epigenome, the tissue-specificity
of epigenetic marks, the stability (or lack thereof) of epigenetic changes over
time and the importance of associating epigenetic changes with changes in
transcription or translation to demonstrate functional consequences. In this
review, we discuss each of these key concepts and provide practical strategies to
mitigate some common pitfalls with the aim of providing a useful guide for future
epigenetic studies in DOHaD.
PMID- 27609593
TI - Psychrobacter pocilloporae sp. nov., isolated from a coral, Pocillopora eydouxi.
AB - Two closely related aerobic, Gram-stain-negative, rod-shaped bacteria (S6-60T and
S6-67) were isolated from the mucus of the coral, Pocilloporaeydouxi, from the
Andaman Sea, India. Heterotrophic growth on marine agar was observed at 4-37
degrees C and at pH 6.5-10.0; optimum growth occurred at 25-30 degrees C and at
pH 7-9. 16S rRNA gene sequence analysis confirmed that the isolates belong to the
genus Psychrobacter; the two isolates shared more than 99.5 % pairwise sequence
similarity. Strain S6-60T showed a maximum 16S rRNA similarity of 98.92 % with
Psychrobacter pacificensis DSM 23406T. DNA-DNA homology between the two isolates,
S6-60T and S6-67, was above 90 %, whereas strain S6-60T showed less than 70 %
homology with closely related type species. The DNA G+C content was 47.7 mol%. It
contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine
and phospholipid as the major polar lipids. C10 : 0, C12 : 0 3OH, C16 : 0, C18 :
1omega9c, C17 : 1omega8c and C16 : 1omega7c were found to be the predominant
fatty acids. Based on a polyphasic analysis, the isolates (S6-60T and S6-67)
represent a novel species of the genus Psychrobacter for which the name
Psychrobacter pocilloporae sp. nov. is proposed with S6-60T(=JCM 31058T=LMG
29157T) as the type strain.
PMID- 27609594
TI - Mycobacterium bovis prosthetic joint infection.
PMID- 27609595
TI - Predictors of mortality among HIV-infected children receiving highly active
antiretroviral therapy.
AB - BACKGROUND AND OBJECTIVES: The mortality rate of HIV-infected children can be
reversed under highly active antiretroviral therapy (HAART). The impact of HAART
on the mortality of HIV-infected children in Cameroon has not been extensively
documented. We aimed to measure the mortality rate of HIV-infected children under
HAART and to identify predictive factors of mortality. METHODS: Retrospective
cohort study of 221 children initiated on HAART from 2005 to 2009 and followed-up
until 2013. Survival data was analyzed using Kaplan Meier method and Cox
regression model to identify independent predictors of child mortality on HAART.
RESULTS: Overall, 9.9% of children (n=22) died over a follow-up period of 755
child-years (mortality of 2.9 per 100 child-years); 70% of deaths occurred during
the first six months of HAART. The probability of survival after four years of
treatment was 88.7% (95% CI=[84.2-93.3]). During the multivariate analysis of
baseline variables, we observed that the WHO clinical stages III and IV (HR: 3.55
[1.09-13.6] and HR: 7.7 [3.07-31.2]) and age<=1year at HAART initiation were
independently associated with death (HR: 2.1 [1.01-5.08]). Neither orphanhood,
baseline CD4 count or hemoglobin level nor low nutritional status predicted death
in this cohort. CONCLUSION: The mortality of children receiving HAART was low
after five years of follow-up and it was strongly associated with WHO stages III
and IV and a younger age at treatment initiation.
PMID- 27609596
TI - Introduction of a PCT-based algorithm to guide antibiotic prescription in COPD
exacerbation.
AB - OBJECTIVES: Prescribing antibiotics for COPD exacerbations is not easy.
Procalcitonin (PCT) is a useful biomarker that helps reduce the rate of
antibiotic therapies. However, its proper cut-off levels are often unknown. We
aimed to assess the impact of a PCT-based algorithm to guide antibiotic therapy
prescription in COPD exacerbations. METHODS: We conducted an observational,
retrospective, and before/after study. We reviewed physician practices regarding
PCT test and antibiotic therapy prescription to all patients hospitalized for
COPD exacerbation. We then analyzed the rate of antibiotic prescriptions and the
number of PCT tests prescribed before and after the introduction of a protocol
validated by previous high-power studies. The primary endpoint was the rate of
antibiotic prescriptions. RESULTS: A total of 124 patients before protocol and
121 patients after protocol were included. Antibiotic prescriptions decreased by
41% after protocol introduction (59% vs. 35%, P<0.001), with no increase in
morbidity and mortality at Day 30. Compliance with protocol was complete in 60%
of cases and partial (no PCT guidance to discontinue antibiotics) in 8% of cases.
Both antibiotic duration (8.3 days vs. 8.7 days) and length of hospital stay (8.5
days vs. 8.3 days, P=0.78) did not change. CONCLUSION: Hospital physicians are
already using PCT-based algorithm to guide antibiotic prescription in COPD
exacerbations. Disseminating information on the appropriate PCT cut-off level to
use to decide whether or not to initiate antibiotics is effective. Its proper use
should be clarified to reduce antibiotic prescriptions to these overexposed
patients.
PMID- 27609598
TI - Slo1 regulates ethanol-induced scrunching in freshwater planarians.
AB - When freshwater planarians are exposed to a low-percentage (0.5%-1%) alcohol
solution, they display a characteristic 'drunken' phenotype. Here we show that
this drunken phenotype is a mixture of cilia-mediated gliding and scrunching, a
muscular-based planarian gait which we recently demonstrated to be triggered by
adverse environmental stimuli. At exogenous ethanol concentrations >=2% (v/v),
planarians become gradually immobilized and ultimately die. Using RNA
interference (RNAi) for targeted gene knockdown, we elucidate the molecular basis
for ethanol sensing and show that the big potassium ion channel SLO1 is necessary
for ethanol sensitivity in planarians. Because slo1(RNAi) animals maintain their
ability to scrunch in response to other adverse triggers, these results suggest
that slo1 specifically regulates ethanol sensitivity and not the scrunching gait
per se. Furthermore, this study demonstrates the ease of performing
pharmacological studies in planarians. Combined with the worms' amenability to
quantitative behavioral assays and targeted gene knockdown, planarians are a
valuable model organism for studying the effect of neuroactive compounds on brain
function and behavior.
PMID- 27609597
TI - In vitro susceptibility to mecillinam of Escherichia coli strains isolated from
the urine of pregnant women.
AB - OBJECTIVES: Pivmecillinam is a safe beta-lactam for use in pregnancy. It has been
widely used for the treatment of lower urinary tract infections (UTIs) in the
Nordic countries where its efficacy, minor impact on the microbiota, and low
level of resistance among the Escherichia coli strains have been proven. However,
susceptibility data related to E. coli involved in asymptomatic bacteriuria and
lower UTIs in pregnant women is lacking. We aimed to support the 2015
recommendations issued by the French Infectious Diseases Society (SPILF) on
gestational UTI, with a particular focus on pivmecillinam. MATERIAL AND METHODS:
Antimicrobial susceptibility testing was performed by 12 hospitals with a
maternity department on 235 E. coli strains isolated from the urine of pregnant
women. Susceptibility to mecillinam was tested by disk diffusion method using the
2015 recommendations of the antibiogram committee of the French microbiology
society (CA-SFM). RESULTS: Global susceptibility to mecillinam was 86.4%.
Susceptibility to mecillinam was 96.5% for strains susceptible to amoxicillin
clavulanic acid and 38.7% for resistant strains. All six extended-spectrum beta
lactamase-producing E. coli strains were susceptible to mecillinam. CONCLUSION:
Given the efficacy and safety of pivmecillinam during pregnancy, it may be used
for the documented treatment of asymptomatic bacteriuria and acute cystitis in
pregnant women. It also represents an alternative for the treatment of multidrug
resistant bacterial infections.
PMID- 27609599
TI - Culturally Relevant Protective and Risk Factors of Youth Risk Behaviors Among
Pakistani and Indian Students in Hong Kong: A Focus Group Study.
AB - PURPOSE: The risk behaviors of Hong Kong ethnic minority students are
understudied. This exploratory qualitative study aimed to explore culturally
nuanced factors for the development and prevention of risk behaviors among
Pakistani and Indian students in Hong Kong. METHOD: Twenty-three students
participated in four focus groups. All interviews were transcribed verbatim and
analyzed using thematic analysis. RESULTS: The participants reported bullying,
delinquency, gambling, alcohol, cigarette, and drug uses as risk behaviors. Four
themes emerged in the development and prevention of risk behaviors: (a) Parental
and peer influence, (b) An unsafe community environment were perceived by the
participants as essential factors for the development of risk behaviors, (c)
Parental monitoring, and (d) Strong religious beliefs were believed as protective
factors for the prevention of risk behaviors. CONCLUSION: Further research and
practice may investigate and focus on the factors embedded in the Hong Kong
ethnic minorities' sociocultural contexts to prevent risk behaviors.
PMID- 27609600
TI - Physiology of Saccharomyces cerevisiae strains isolated from Brazilian biomes:
new insights into biodiversity and industrial applications.
AB - Fourteen indigenous Saccharomyces cerevisiae strains isolated from the barks of
three tree species located in the Atlantic Rain Forest and Cerrado biomes in
Brazil were genetically and physiologically compared to laboratory strains and to
strains from the Brazilian fuel ethanol industry. Although no clear correlation
could be found either between phenotype and isolation spot or between phenotype
and genomic lineage, a set of indigenous strains with superior industrially
relevant traits over commonly known industrial and laboratory strains was
identified: strain UFMG-CM-Y257 has a very high specific growth rate on sucrose
(0.57 +/- 0.02 h-1), high ethanol yield (1.65 +/- 0.02 mol ethanol mol hexose
equivalent-1), high ethanol productivity (0.19 +/- 0.00 mol L-1 h-1), high
tolerance to acetic acid (10 g L-1) and to high temperature (40 degrees C).
Strain UFMG-CM-Y260 displayed high ethanol yield (1.67 +/- 0.13 mol ethanol mol
hexose equivalent-1), high tolerance to ethanol and to low pH, a trait which is
important for non-aseptic industrial processes. Strain UFMG-CM-Y267 showed high
tolerance to acetic acid and to high temperature (40 degrees C), which is of
particular interest to second generation industrial processes.
PMID- 27609601
TI - tRNA-derived short RNAs bind to Saccharomyces cerevisiae ribosomes in a stress
dependent manner and inhibit protein synthesis in vitro.
AB - Recently, a number of ribosome-associated non-coding RNAs (rancRNAs) have been
discovered in all three domains of life. In our previous studies, we have
described several types of rancRNAs in Saccharomyces cerevisiae, derived from
many cellular RNAs, including mRNAs, rRNAs, tRNAs and snoRNAs. Here, we present
the evidence that the tRNA fragments from simple eukaryotic organism S.
cerevisiae directly bind to the ribosomes. Interestingly, rancRNA-tRFs in yeast
are derived from both, 5'- and 3'-part of the tRNAs and both types of tRFs
associate with the ribosomes in vitro The location of tRFs within the ribosomes
is distinct from classical A- and P-tRNA binding sites. Moreover, 3'-tRFs bind to
the distinct site than 5'-tRFs. These interactions are stress dependent and as a
consequence, provoke regulation of protein biosynthesis. We observe strong
correlation between tRF binding to the ribosomes and inhibition of protein
biosynthesis in particular environmental conditions. These results implicate the
existence of an ancient and conserved mechanism of translation regulation with
the involvement of ribosome-associating tRNA-derived fragments.
PMID- 27609602
TI - Null mutants of Candida albicans for cell-wall-related genes form fragile
biofilms that display an almost identical extracellular matrix proteome.
AB - By two-dimensional gel electrophoresis (2-DE) and mass spectrometry, we have
characterized the polypeptide species present in extracts obtained by 60% ethanol
treatment of whole mature (48 h) biofilms formed by a reference strain (CAI4
URA3) and four Candida albicans null mutants for cell-wall-related genes (ALG5,
CSA1, MNN9 and PGA10) Null mutants form fragile biofilms that appeared partially
split and weakly attached to the substratum contrary to those produced by the
reference strain. An almost identical, electrophoretic profile consisting of
about 276 spots was visualized in all extracts examined. Proteomic analysis led
to the identification of 131 polypeptides, corresponding to 86 different protein
species, being the rest isoforms-83 displayed negative hydropathic indexes and 82
lack signal peptide. The majority of proteins appeared at pI between 4 and 6, and
molecular mass between 10 and 94 kDa. The proteins identified belonged to the
following Gene Ontology categories: 21.9% unknown molecular function, 16.2%
oxidoreductase activity, 13.3% hydrolase activity and 41.8% distributed between
other different GO categories. Strong defects in biofilm formation appreciated in
the cell-wall mutant strains could be attributed to defects in aggregation due to
abnormal cell wall formation rather than to differences in the biofilm
extracellular matrix composition.
PMID- 27609603
TI - Food and drink consumption among 1-5-year-old Los Angeles County children from
households receiving dual SNAP and WIC v. only WIC benefits.
AB - OBJECTIVE: The Supplemental Nutrition Assistance Program (SNAP) and the Special
Supplemental Nutrition Program for Women, Infants, and Children (WIC) are two of
the more well-known food assistance programmes in the USA. The current study
describes food consumption patterns of children aged 1-5 years living in
households dually enrolled in these two programmes v. households enrolled only in
WIC. DESIGN: Food consumption and SNAP participation were assessed using data
from the 2014 Survey of Los Angeles County (LAC) WIC Participants and the Follow
Up Survey of the same households that were also SNAP beneficiaries. Telephone
interviews were conducted with WIC parents regarding each child's (i.e.
beneficiary's) food consumption patterns. Follow-up interviews were conducted
with those who reported receiving SNAP. Multivariable regression analyses were
performed to assess the relationships between food and beverage consumption and
dual v. single food assistance programme participation. SETTING: LAC, California.
SUBJECTS: Children of WIC-enrolled households in LAC during 2014 (n 3248). This
included a sub-sample of dual WIC- and SNAP-enrolled households (n 1295). Survey
participants were the beneficiaries' parents. RESULTS: Children from dually
enrolled households consumed 1.03 (P<0.05) and 1.04 (P<0.01) more servings of
fruits and vegetables daily respectively, 1.07 more sugar-sweetened beverages
daily (P<0.001) and ate sweets/sweetened foods 1.04 more times daily (P<0.001)
than children from households participating only in WIC. CONCLUSIONS: Results
suggest that SNAP+WIC enrolment is associated with increased consumption of both
healthy foods and foods containing minimal nutritional value. Complementary
nutrition education efforts across the two programmes may help beneficiaries
maximize healthful food purchases with SNAP dollars.
PMID- 27609604
TI - Addition of immunosuppression to comprehensive supportive care did not benefit
patients with IgA nephropathy.
PMID- 27609605
TI - The European Association for Palliative Care White Paper on euthanasia and
physician-assisted suicide: Dodging responsibility.
PMID- 27609606
TI - From neighbour to carer: An exploratory study on the role of non-kin-carers in
end-of-life care at home for older people living alone.
AB - BACKGROUND: A growing number of older people are living in single households.
They form a disadvantaged group within society as regards staying at home, most
likely towards the end-of-life. It is mainly non-kin-carers who try to fulfil
older people's desire for a home death, but very little is known about the
challenges they face during their involvement. AIM: Getting insight into the
engagement of non-kin-carers in the support for older people living alone, and a
better understanding of the challenges they have to manage in end-of-life care.
DESIGN: Exploratory qualitative design; perspectives of non-kin-carers were
collected through personal in-depth interviews ( n = 15) retrospectively.
SETTING: Home care, urban and rural areas in Austria Findings: A slow and subtle
transition into care is what characterizes non-kin-care relationships which show
differences between friends and neighbours. Towards the end of life, the main
challenges emerged around increased physical care needs, issues of decision
making and facing the process of dying. Prior experiences with the latter, which
most of the involved carers had, influenced non-kin-carers' steadiness to allow
home death and so did reliable formal support, particularly from specialized
palliative care teams. CONCLUSION: Support of older people living alone, in
particular until the last stage of life, comes along with multiple efforts.
Respectful and supporting relationships between professional carers and non-kin
carers are vital to keep non-kin-carers involved.
PMID- 27609608
TI - Inhibition of tachykinin NK1 receptor using aprepitant induces apoptotic cell
death and G1 arrest through Akt/p53 axis in pre-B acute lymphoblastic leukemia
cells.
AB - Increasing number of genetic and cancer biology studies indicated a prominent
role for tachykinin NK1 receptor (NK1R) in cancer cell growth and survival.
Considering the fact that neoplastic lymphoid precursors in acute lymphoblastic
leukemia (ALL) carry a three- to four-fold NK1R expression as compared to normal
lymphocytes, using NK1R antagonist seems to be noteworthy in the treatment of ALL
patients. In this study, we found that inhibition of NK1R with aprepitant, a
selective high-affinity antagonist of the human NK1R, exerts cytotoxic and anti
proliferative effects against pre-B ALL-derived Nalm-6 cells either as single
drug or in combination with doxorubicin. Our data showed that treatment of the
cells with the inhibitor resulted in apoptotic cell death, at least partly,
through abrogation of PI3K/Akt pathway, as revealed by the reduction of
phospho/total Akt ratio. In agreement with the inhibitory effect on Akt, we also
found that aprepitant increased the expression level of p21 and p27, which in
turn leads to the induction of G1 cell cycle arrest. Overall, this study
recommends mechanistic pathways by which inhibition of NK1R can augment apoptotic
cell death through a plausible p53-dependent pathway rather than NF-kappaB
depended mechanism in pre-B ALL cells; however, further studies are needed to
better characterize the application of NK1R inhibition in clinical cancer
treatment.
PMID- 27609611
TI - Does a dual attending surgeon strategy confer additional benefit for posterior
selective thoracic fusion in Lenke 1 and 2 adolescent idiopathic scoliosis (AIS)?
A prospective propensity matching score analysis.
AB - BACKGROUND CONTEXT: With an increased cost of adolescent idiopathic scoliosis
(AIS) surgery over the past 10 years, improvement of patient safety and
optimization of the surgical management of AIS has become an important need. A
dual attending surgeon strategy resulted in reduction of blood loss and
complication rate. PURPOSE: This study aimed to investigate the perioperative
outcome of posterior selective thoracic fusion in Lenke 1 and 2 AIS patients
comparing a single versus a dual attending surgeon strategy. STUDY DESIGN: A
prospective cohort study was carried out. PATIENT SAMPLE: The study sample
comprised 60 patients OUTCOME MEASURE: Operative duration, blood loss,
postoperative hemoglobin, need for transfusion, morphine usage, and duration of
hospital stay were the outcome measures. METHODS: A total of 116 patients who
underwent posterior selective thoracic fusion from two centers were prospectively
recruited. The patients were grouped into Group 1 (single surgeon) and Group 2
(two surgeons). One-to-one matching analysis using "propensity score-matched
cohort patient sampling method" was done for age, gender, height, weight,
preoperative Cobb angle, number of fusion level, and Lenke classification. The
outcome measures included operative duration, blood loss, postoperative
hemoglobin, need for transfusion, morphine usage, and duration of hospital stay.
This study was self-funded with no conflict of interest. RESULTS: From 86
patients who were operated by the two surgeons (Group 2), 30 patients were
matched with 30 patients who were operated by a single surgeon (Group 1). Group 2
(164.0+/-25.7 min) has a significantly shorter operation duration (p=.000)
compared with Group 1 (257.3+/-51.4 min). The total blood loss was significantly
more (p=.009) in Group 1 (1254.7+/-521.5 mL) compared with Group 2 (893.7+/-518.4
mL). There were seven patients (23.3%) in Group 1 who received allogenic blood
transfusion (p<.05). The morphine usage and average hospital stay were
significantly lower in Group 2, 22.4+/-10.7 mg and 3.4+/-0.7 days, respectively
(p<.05). In Group 1, there was one patient who developed a superficial wound
infection. No other major complications were noted. CONCLUSIONS: A dual attending
surgeon strategy was superior to a single surgeon strategy in posterior selective
thoracic fusion in Lenke 1 and 2 AIS patients and will lead to a faster
operation, reduced intraoperative blood loss, reduced risk of allogenic
transfusion, reduced morphine requirement, and shorter hospital stay.
PMID- 27609609
TI - Neurochemical factors associated with the antidepressant-like effect of flavonoid
chrysin in chronically stressed mice.
AB - Chrysin is a flavonoid which is found in bee propolis, honey and various plants.
Antidepressant-like effect of chrysin in chronically stressed mice was previously
demonstrated by our group. Conversely, neurochemical factors associated with this
effect require further investigations. Thus, we investigated the possible
involvement of pro-inflammatory cytokines, kynurenine pathway (KP), 5
hydroxytryptamine (5-HT) metabolism and caspases activities in the effect of
chrysin in mice exposed to unpredictable chronic stress (UCS). UCS applied for 28
days induced a depressive-like behavior, characterized by decrease in the time of
grooming in the splash test and by increase in the immobility time in the tail
suspension test. Oral treatment with chrysin (5 or 20mg/kg, 28 days), similarly
to fluoxetine (10mg/kg, positive control), culminated in the prevention of these
alterations. UCS elevated plasma levels of corticotropin-releasing hormone and
adrenocorticotropic hormone, as well the tumor necrosis factor-alpha, interleukin
1beta, interleukin-6 and kynurenine levels in the prefrontal cortex (PFC) and
hippocampus (HP). UCS induced the decrease in the 5-HT levels in the HP and the
increase in the indoleamine-2,3-dioxygenase, caspase 3 and 9 activities in the
PFC and HP. Treatment with chrysin, similarly to fluoxetine, promoted the
attenuation of these alterations occasioned by UCS. These results corroborated
with the antidepressant potential of chrysin in the treatment of psychiatric
diseases. Furthermore, this work indicated the association of pro-inflammatory
cytokines synthesis, KP, 5-HT metabolism and caspases activities with the action
exercised by chrysin in mice exposed to UCS.
PMID- 27609612
TI - Mapping Indicators of Toxicity for Polycyclic Aromatic Compounds in the
Atmosphere of the Athabasca Oil Sands Region.
AB - Extracts of passive air samples collected from 15 passive sampling network sites
across the Athabasca Oil Sands region were used to explore the application of in
vitro assays for mutagenicity (Salmonella mutation assays) and cytotoxicity
(lactate dehydrogenase assay) to assess the toxicity of the air mixture. The air
monitoring of polycyclic aromatic compounds (PACs) and PAC transformation
products, including nitrated polycyclic aromatic hydrocarbons (NPAHs) and
oxygenated polycyclic aromatic hydrocarbons (OPAHs) was then linked to the
potential toxicity of air. The PACs in air during April to May 2014 were elevated
near mining activities and declined with distance from the source region, whereas
NPAHs and OPAHs exhibited a more variable spatial distribution with the highest
levels in Fort McMurray. Overall, the air samples exhibited a weak mutagenicity.
The highest indirect-acting mutagenicity was observed for sites closest to mining
activities; however, the indirect-acting mutagenicity did not decline sharply
with distance from mining areas. Indirect-acting mutagenicity was strongly
correlated with levels of total PACs, benzo(a)pyrene equivalent mass, and OPAHs.
Most of the samples exhibited cytotoxic potential, but the magnitude of the
response was variable across the sample region and did not correlate with levels
of target analytes. This indicates that PACs and PAC derivatives were not a major
contributor to the cytotoxicity observed in the air samples.
PMID- 27609610
TI - High resolution imaging reveals heterogeneity in chromatin states between cells
that is not inherited through cell division.
AB - BACKGROUND: Genomes of eukaryotes exist as chromatin, and it is known that
different chromatin states can influence gene regulation. Chromatin is not a
static structure, but is known to be dynamic and vary between cells. In order to
monitor the organisation of chromatin in live cells we have engineered
fluorescent fusion proteins which recognize specific operator sequences to tag
pairs of syntenic gene loci. The separation of these loci was then tracked in
three dimensions over time using fluorescence microscopy. RESULTS: We established
a work flow for measuring the distance between two fluorescently tagged, syntenic
gene loci with a mean measurement error of 63 nm. In general, physical separation
was observed to increase with increasing genomic separations. However, the extent
to which chromatin is compressed varies for different genomic regions. No
correlation was observed between compaction and the distribution of chromatin
markers from genomic datasets or with contacts identified using capture based
approaches. Variation in spatial separation was also observed within cells over
time and between cells. Differences in the conformation of individual loci can
persist for minutes in individual cells. Separation of reporter loci was found to
be similar in related and unrelated daughter cell pairs. CONCLUSIONS: The
directly observed physical separation of reporter loci in live cells is highly
dynamic both over time and from cell to cell. However, consistent differences in
separation are observed over some chromosomal regions that do not correlate with
factors known to influence chromatin states. We conclude that as yet unidentified
parameters influence chromatin configuration. We also find that while
heterogeneity in chromatin states can be maintained for minutes between cells, it
is not inherited through cell division. This may contribute to cell-to-cell
transcriptional heterogeneity.
PMID- 27609613
TI - High intensity exercise training in heart failure: Understanding the exercise
"overdose".
PMID- 27609614
TI - Are recent statin recommendations to employ fixed doses and abandon targets
effective for treatment of hypercholesterolaemia? Investigation based on number
needed to treat.
AB - BACKGROUND: Assessed by number needed to treat (NNT) to prevent one event, it was
previously shown that for those at similar atherosclerotic cardiovascular disease
(CVD) risk, the benefit accruing from treating people with higher cholesterol
levels with statins is greater than for those with lower levels. METHOD: By
estimating NNT from both the absolute atherosclerotic cardiovascular risk and the
pre-treatment low density lipoprotein cholesterol (LDL-C) concentration, recent
recommendations for fixed dose high and moderate intensity statin treatment in
the primary and secondary prevention of CVD were compared with cholesterol
lowering therapy aimed at a target LDL-C. RESULTS: We report that the USA and UK
recommendations to employ a fixed dose of atorvastatin 20 mg daily for primary
prevention will produce good results in people with low cholesterol levels, but
are a disadvantage for those with higher levels who benefit more from a
therapeutic target and statin dose titration and, where necessary, adjunctive
cholesterol-lowering therapy to achieve this target. The higher dose of
atorvastatin 80 mg daily with no target recommended for secondary prevention is
generally more effective than aiming for a LDL-C goal except in people with
particularly high cholesterol. CONCLUSION: For optimum clinical effectiveness,
initial LDL-C concentration must be considered in deciding whether a target will
allow a greater decrease in LDL-C and thus a lower NNT than a fixed dose regimen.
Individual variation in the LDL-C response to statins also makes post-treatment
cholesterol measurement essential.
PMID- 27609607
TI - The under reporting of recruitment strategies in research with children with life
threatening illnesses: A systematic review.
AB - BACKGROUND: Researchers report difficulties in conducting research with children
and young people with life-limiting conditions or life-threatening illnesses and
their families. Recruitment is challenged by barriers including ethical,
logistical and clinical considerations. AIM: To explore how children and young
people (aged 0-25 years) with life-limiting conditions or life-threatening
illnesses and their families were identified, invited and consented to research
published in the last 5 years. DESIGN: Systematic review. DATA SOURCES: MEDLINE,
PsycINFO, Web of Science, Sciences Citation Index and SCOPUS were searched for
original English language research published between 2009 and 2014, recruiting
children and young people with life-limiting conditions or life-threatening
illness and their families. RESULTS: A total of 215 studies - 152 qualitative, 54
quantitative and 9 mixed methods - were included. Limited recruitment information
but a range of strategies and difficulties were provided. The proportion of
eligible participants from those screened could not be calculated in 80% of
studies. Recruitment rates could not be calculated in 77%. A total of 31% of
studies recruited less than 50% of eligible participants. Reasons given for non
invitation included missing clinical or contact data, or clinician judgements of
participant unsuitability. Reasons for non-participation included lack of
interest and participants' perceptions of potential burdens. CONCLUSION: All
stages of recruitment were under reported. Transparency in reporting of
participant identification, invitation and consent is needed to enable
researchers to understand research implications, bias risk and to whom results
apply. Research is needed to explore why consenting participants decide to take
part or not and their experiences of research recruitment.
PMID- 27609615
TI - Eco-social processes influencing infectious disease emergence and spread.
AB - The complexity and connectedness of eco-social processes have major influence on
the emergence and spread of infectious diseases amongst humans and animals. The
disciplinary nature of most research activity has made it difficult to improve
our understanding of interactions and feedback loops within the relevant systems.
Influenced by the One Health approach, increasing efforts have recently been made
to address this knowledge gap. Disease emergence and spread is strongly
influenced by host density and contact structures, pathogen characteristics and
pathogen population and molecular evolutionary dynamics in different host
species, and host response to infection. All these mechanisms are strongly
influenced by eco-social processes, such as globalization and urbanization, which
lead to changes in global ecosystem dynamics, including patterns of mobility,
human population density and contact structures, and food production and
consumption. An improved understanding of epidemiological and eco-social
processes, including their interdependence, will be essential to be able to
manage diseases in these circumstances. The interfaces between wild animals,
domestic animals and humans need to be examined to identify the main risk
pathways and put in place appropriate mitigation. Some recent examples of
emerging infectious disease are described to illustrate eco-social processes that
are influencing disease emergence and spread.
PMID- 27609617
TI - Genome analysis and pathogenicity of reticuloendotheliosis virus isolated from a
contaminated vaccine seed against infectious bursal disease virus: first report
in China.
AB - Specific-pathogen-free (SPF) chickens were inoculated with the virus seed of an
infectious bursal disease virus (IBDV)-attenuated vaccine, and positive
reticuloendotheliosis virus (REV) antibody levels were subsequently detected in
the chicken sera, indicating potential REV contamination of the vaccine. After
neutralization with IBDV-positive blood serum, the vaccine was inoculated into DF
1 cells for REV isolation and identification. An REV strain, designated IBD
C1605, was identified using an immunofluorescence assay test. Three pairs of
primers were employed for the amplification, cloning and sequencing of three
overlapping fragments of the IBD-C1605 genome, and the whole-genome sequence of
this isolate was obtained after gene assembly. The genome was 8362 base pairs
(nt) in length and its homology with the nucleotide sequences of different
reference strains varied between 94.2 and 99.2 %. Isolate IBD-C1605 was
inoculated into 1-day-old SPF chickens to observe its pathogenicity. Infection
with this organism slowed down the weight gain of SPF chickens and caused atrophy
of their immune organs, such as the bursa of Fabricius and thymus gland.
Furthermore, the chicken antibody levels decreased significantly after Newcastle
disease virus and avian influenza virus subtype H9 vaccine immunization. This is
the first report on the isolation and identification of REV from attenuated
vaccine virus seeds in China, and is also the first study on the pathogenicity of
REV from a contaminated vaccine in China. Our findings contribute towards a
better understanding of the detrimental effects of vaccine contamination with
exogenous viruses such as REV.
PMID- 27609616
TI - Suppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic
Nephropathy.
AB - Diabetes is the main cause of CKD and ESRD worldwide. Chronic activation of Janus
kinase and signal transducer and activator of transcription (STAT) signaling
contributes to diabetic nephropathy by inducing genes involved in leukocyte
infiltration, cell proliferation, and extracellular matrix accumulation. This
study examined whether a cell-permeable peptide mimicking the kinase-inhibitory
region of suppressor of cytokine signaling-1 (SOCS1) regulatory protein protects
against nephropathy by suppressing STAT-mediated cell responses to diabetic
conditions. In a mouse model combining hyperglycemia and hypercholesterolemia
(streptozotocin diabetic, apoE-deficient mice), renal STAT activation status
correlated with the severity of nephropathy. Notably, compared with
administration of vehicle or mutant inactive peptide, administration of the SOCS1
peptidomimetic at either early or advanced stages of diabetes ameliorated STAT
activity and resulted in reduced serum creatinine level, albuminuria, and renal
histologic changes (mesangial expansion, tubular injury, and fibrosis) over time.
Mice treated with the SOCS1 peptidomimetic also exhibited reduced kidney
leukocyte recruitment (T lymphocytes and classic M1 proinflammatory macrophages)
and decreased expression levels of proinflammatory and profibrotic markers that
were independent of glycemic and lipid changes. In vitro, internalized peptide
suppressed STAT activation and target gene expression induced by inflammatory and
hyperglycemic conditions, reduced migration and proliferation in mesangial and
tubuloepithelial cells, and altered the expression of cytokine-induced macrophage
polarization markers. In conclusion, our study identifies SOCS1 mimicking as a
feasible therapeutic strategy to halt the onset and progression of renal
inflammation and fibrosis in diabetic kidney disease.
PMID- 27609618
TI - Prenatal Evaluation, Imaging Features, and Neurodevelopmental Outcome of
Prenatally Diagnosed Periventricular Pseudocysts.
AB - BACKGROUND AND PURPOSE: Periventricular pseudocysts are cystic cavities that lack
the ependymal cell lining found in true cysts. The aim of this study was to
characterize periventricular pseudocysts and related findings and their
neurodevelopmental outcome. MATERIALS AND METHODS: This was a retrospective study
of periventricular pseudocysts detected prenatally on fetal MR imaging in 26
fetuses. The fetuses were divided into group A (n = 8), which included cases with
isolated periventricular pseudocysts, and group B (n = 18), which included cases
of periventricular pseudocysts with additional findings. Cases were further
subdivided into connatal cysts and subependymal pseudocysts. Data collected
included prenatal history, MR imaging features, sonographic follow-up, and
neurodevelopmental outcome. RESULTS: All cases in group A (n = 8) had a normal
outcome. In group B (n = 18), 6 pregnancies were terminated and 2 had an abnormal
outcome. Both cases with an abnormal outcome involved patients with subependymal
pseudocysts. No significant association was found between the morphologic
features on MR imaging and the neurodevelopmental outcome. CONCLUSIONS:
Neurodevelopmental outcome in cases of isolated periventricular pseudocysts
detected prenatally appears to be normal. A detailed evaluation should be
performed to rule out additional brain findings, chromosomal aberration, and
fetal malformation. This evaluation should include the following: maternal TORCH
status, detailed fetal sonographic anatomic evaluation, fetal echocardiogram,
fetal brain MR imaging, amniocentesis and karyotyping/comparative genomic
hybridization, and genetic counseling. Additional findings on MR imaging,
including mild-to-moderate dilated ventricles, asymmetric ventricles, or T2
hyperintense signal in the white matter without other findings or major fetal
abnormality, appear to be benign. Connatal cysts appear to be benign.
PMID- 27609619
TI - Spine Cryoablation: A Multimodality Image-Guided Approach for Tumors Adjacent to
Major Neural Elements.
AB - We report percutaneous cryoablation of spine tumors in 7 consecutive patients (5
men, 2 women [mean age, 47 years; range, 17-68 years]) by using intraprocedural
image monitoring of ice ball margins to protect adjacent neural elements.
Complete tumor ablation was achieved in all patients without neurologic
complication. Pain relief was achieved in 4 of 5 (80%) patients; the patient with
persistent pain was later found to have enlarging metastases at other sites.
PMID- 27609620
TI - Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.
AB - BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis,
is typically associated with volume loss of the affected hemisphere of the brain.
Our aim was to apply automated quantitative volumetric MR imaging analyses to
patients diagnosed with Rasmussen encephalitis, to determine the predictive value
of lobar volumetric measures and to assess regional atrophy differences as well
as monitor disease progression by using these measures. MATERIALS AND METHODS:
Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied.
We used 2 control groups: one with 42 age- and sex-matched healthy subjects and
the other with 42 epileptic patients without Rasmussen encephalitis with the same
disease duration as patients with Rasmussen encephalitis. Volumetric analysis was
performed on T1-weighted images by using BrainSuite. Ratios of volumes from the
affected hemisphere divided by those from the unaffected hemisphere were used as
input to a logistic regression classifier, which was trained to discriminate
patients from controls. Using the classifier, we compared the predictive accuracy
of all the volumetric measures. These ratios were used to further assess regional
atrophy differences and correlate with epilepsy duration. RESULTS:
Interhemispheric and frontal lobe ratios had the best prediction accuracy for
separating patients with Rasmussen encephalitis from healthy controls and patient
controls without Rasmussen encephalitis. The insula showed significantly more
atrophy compared with all the other cortical regions. Patients with longitudinal
scans showed progressive volume loss in the affected hemisphere. Atrophy of the
frontal lobe and insula correlated significantly with epilepsy duration.
CONCLUSIONS: Automated quantitative volumetric analysis provides accurate
separation of patients with Rasmussen encephalitis from healthy controls and
epileptic patients without Rasmussen encephalitis, and thus may assist the
diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included
as part of follow-up for patients with Rasmussen encephalitis to assess disease
progression.
PMID- 27609621
TI - Preradiotherapy MR Imaging: A Prospective Pilot Study of the Usefulness of
Performing an MR Examination Shortly before Radiation Therapy in Patients with
Glioblastoma.
AB - BACKGROUND AND PURPOSE: Current protocols in patients with glioblastoma include
performing an MR examination shortly after surgery and then 2-6 weeks after
ending concomitant chemoradiotherapy. The assessment of this first
postradiotherapy examination is challenging because the pseudoprogression
phenomenon may appear. The aim of this study was to explore if performing an MR
examination shortly before radiation therapy (preradiotherapy MR imaging) could
improve the radiologic assessment of patients with glioblastoma. MATERIALS AND
METHODS: A preradiotherapy MR imaging examination was prospectively performed
before the start of radiation therapy in 28 consecutive patients with
glioblastoma who had undergone surgical resection. Tumor response to
chemoradiotherapy was assessed twice: with the early postoperative MR examination
as baseline and with the preradiotherapy MR imaging examination as baseline. In
addition, tumor growth in the preradiotherapy MR imaging examination was
evaluated, and its correlation with patient survival was assessed with Kaplan
Meier analysis and Cox regression. RESULTS: Tumor progression after radiation
therapy was found in 16 patients, corresponding to pseudoprogression in 7 of them
(44%). Four assessments of pseudoprogression switched to partial response or
stable disease when preradiotherapy MR imaging was the baseline examination, and
the ratio of pseudoprogression was reduced to 25% (3 of 12). Significant
differences in survival were found when patients were stratified according to the
pattern of tumor growth on preradiotherapy MR imaging (median overall survival
"no-growth," 837 days; "focal-growth," 582 days; "global-growth," 344 days; P =
.001). CONCLUSIONS: Performing a preradiotherapy MR imaging examination may
improve the clinical management of patients with glioblastoma by reducing the
ratio of pseudoprogression assessments and providing prognostic information.
PMID- 27609622
TI - Training the Next Generation of Latino Health Researchers: A Multilevel,
Transdisciplinary, Community-Engaged Approach.
AB - Reducing health disparities is a national public health priority. Latinos
represent the largest racial/ethnic minority group in the United States and
suffer disproportionately from poor health outcomes, including cardiovascular
disease risk. Academic training programs are an opportunity for reducing health
disparities, in part by increasing the diversity of the public health workforce
and by incorporating training designed to develop a skill set to address health
disparities. This article describes the Training and Career Development Program
at the UCLA Center for Population Health and Health Disparities: a multilevel,
transdisciplinary training program that uses a community-engaged approach to
reduce cardiovascular disease risk in two urban Mexican American communities.
Results suggest that this program is effective in enhancing the skill sets of
traditionally underrepresented students to become health disparities researchers
and practitioners.
PMID- 27609623
TI - A Culturally Responsive Approach to Improving Replication of a Youth Sexual
Health Program.
AB - Youth-serving agencies continually turn to evidence-based interventions that have
been empirically assessed for effectiveness in influencing young people's lives,
particularly those living in communities with considerable health inequities.
Replicating promising evidence-based interventions requires thoughtful adaptation
and modification to better fit participants' sociocultural context and to enhance
their learning experiences. Due to the restrictive nature of a replication model,
adaptations to the intervention curriculum must be minimized during full
implementation. Implementers must find innovative ways to ensure content is
relevant and engaging to participants without altering core elements of the
curriculum. This article describes practical best practice strategies used in
implementing a sexual health education program among socioculturally diverse
youth in a northeastern city in the United States. The implementing agency
applied Richard, Brown and Forde's framework for culturally responsive pedagogy
as a heuristic approach to describe the application of implementation practices
across three dimensions: institutional, personal, and instructional. The results
not only highlight successful culturally responsive practices that enhanced the
implementation process but also acknowledge areas in which such practices proved
daunting to implement.
PMID- 27609625
TI - Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute
psychiatric care.
AB - BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may
be challenging to distinguish from primary psychiatric disorders. The
significance of anti-neuronal antibodies in psychiatric patients without clear
evidence of autoimmune encephalitis is unknown. We investigated the serum
prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients
admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients
admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set
according to International Classification of Diseases (ICD)-10 criteria. Antibody
analysis was performed with an indirect immunofluorescence test for N-methyl d
aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies
of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti
neuronal autoantibodies were found in 11.6% of patients: NMDAR antibodies in
7.6%, contactin-associated protein-like 2 (CASPR2) antibodies in 2.5%, glutamic
acid decarboxylase-65 (GAD65) antibodies in 1.9%, and alpha-amino-3-hydroxy-5
methyl-4-isoxazolepropionic acid (AMPA) receptor antibodies in 0.1%. Leucine-rich
glioma-inactivated protein-1 (LGI1) and gamma-aminobutyric acid B (GABAB)
receptor antibodies were not detected. NMDAR antibodies of class IgG were present
in five patients only (0.5%). NMDAR antibodies of all Ig classes were equally
prevalent in patients with and without psychosis. There were no significant
differences in antibody prevalence in the different diagnostic categories, except
for a higher odds ratio of being NMDAR antibody positive for patients without a
specific psychiatric diagnosis. CONCLUSIONS: NMDAR IgG autoantibodies, which are
known to be strongly associated with anti-NMDAR encephalitis, were rarely found.
CASPR2 and GAD65 antibodies were more frequently encountered in the present study
than previously reported. Further research on the clinical significance of anti
neuronal autoantibodies in patients with acute psychiatric symptoms is needed.
PMID- 27609626
TI - Effect of Li Adsorption on the Electronic and Hydrogen Storage Properties of
Acenes: A Dispersion-Corrected TAO-DFT Study.
AB - Due to the presence of strong static correlation effects and noncovalent
interactions, accurate prediction of the electronic and hydrogen storage
properties of Li-adsorbed acenes with n linearly fused benzene rings (n = 3-8)
has been very challenging for conventional electronic structure methods. To meet
the challenge, we study these properties using our recently developed thermally
assisted-occupation density functional theory (TAO-DFT) with dispersion
corrections. In contrast to pure acenes, the binding energies of H2 molecules on
Li-adsorbed acenes are in the ideal binding energy range (about 20 to 40 kJ/mol
per H2). Besides, the H2 gravimetric storage capacities of Li-adsorbed acenes are
in the range of 9.9 to 10.7 wt%, satisfying the United States Department of
Energy (USDOE) ultimate target of 7.5 wt%. On the basis of our results, Li
adsorbed acenes can be high-capacity hydrogen storage materials for reversible
hydrogen uptake and release at ambient conditions.
PMID- 27609624
TI - A Randomized Controlled Trial of a Trauma-Informed Support, Skills, and
Psychoeducation Intervention for Survivors of Torture and Related Trauma in
Kurdistan, Northern Iraq.
AB - Supportive counseling type interventions are frequently provided to meet the
mental health needs of populations in emergency and post-conflicts contexts, but
it has seldom been rigorously evaluated. Existing evaluations from low- and
middle-income countries provide mixed evidence of effectiveness. While Iraqi
Kurdistan experienced relative stability following the fall of Saddam Hussein's
government, the population in the northern Dohuk region has continued to
experience periodic violence due to conflicts with neighboring Turkey as well as
more recent ISIS-associated violence. We evaluated the impact of a trauma
informed support, skills, and psychoeducation intervention provided by community
mental health workers (CMHWs) on depressive symptoms and dysfunction (primary
outcomes) as well as post-traumatic stress, traumatic grief, and anxiety symptoms
(secondary outcomes). Between June 2009 and June 2010, 295 adults were screened;
209 (71%) met eligibility criteria (trauma exposure and a symptom severity score
indicating significant distress and functional impairment, among others) and
consented to participate. Of these, 159 were randomized to supportive counseling
while 50 were randomized to a waitlist control condition. Comparing average
symptom severity scores post-treatment among those in the intervention group with
those in the waitlist control group, the supportive counseling program had
statistically and clinically significant impacts on the primary outcomes of
depression (Cohen's d, 0.57; P = .02) and dysfunction (Cohen's d, 0.53; P = .03)
and significant but smaller impacts on anxiety. Although studies by the same
research team of psychotherapeutic interventions in other parts of Kurdistan and
in southern Iraq found larger effects, this study adds to the global research
literature on mental health and psychosocial support and shows that a well
trained and supervised program of trauma-informed support, skills, and
psychoeducation that emphasizes the therapeutic relationship can also be
effective.
PMID- 27609627
TI - Offensive strategies in the European Football Championship 2012.
AB - The aim of this study was to identify the independent and interactive effects of
possession strategy, pitch location, and game period on the offensive actions
performed by the winning teams in the 2012 European Football Championship. The
non-clinical magnitude-based inferences method was used to interpret the true
effect of the performance indicators on the response variable. The offensive team
possessions were grouped into winning (n = 2035) and losing (n = 2071). The
winning teams performed offensive processes mainly using the possession play
strategy (OR: 0.75, very likely negative effect of the direct play). When the
analysis included the pitch location, negative interaction effect was found for
the direct play, which ended up in the central path (OR: 0.70, very likely
negative effect). On the contrary, the direct play in the second half of the
match seemed to produce an effect on the probability of the winning teams
performing offensive processes (OR: 1.59, most likely positive effect). The
results of multivariate analyses showed that the offensive team possession
profiles required a careful investigation because the possession strategy changed
under the conjoint effect of pitch location and game period.
PMID- 27609629
TI - CLABSI Risk Factors in the NICU: Potential for Prevention: A PICNIC Study.
AB - OBJECTIVE Central-line-associated bloodstream infections (CLABSI) are an
important cause of morbidity and mortality in neonates. We aimed to determine
whether intra-abdominal pathologies are an independent risk factor for CLABSI.
METHODS We performed a retrospective matched case-control study of infants
admitted to the neonatal intensive care units (NICUs) of the Montreal Children's
Hospital (Montreal) and the Royal Alexandra Hospital, Edmonton, Canada. CLABSI
cases that occurred between April 2009 and March 2014 were identified through
local infection control databases. For each case, up to 3 controls were matched
(National Healthcare Safety Network [NHSN] birth weight category, chronological
age, and central venous catheter (CVC) dwell time at the time of CLABSI onset).
Data were analyzed using conditional logistic regression. RESULTS We identified
120 cases and 293 controls. According to a matched univariate analysis, the
following variables were significant risk factors for CLABSI: active intra
abdominal pathology (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.8
6.4), abdominal surgery in the prior 7 days (OR, 3.5; 95% CI, 1.0-10.9); male sex
(OR, 1.7; 95% CI, 1.1-2.6) and >=3 heel punctures (OR, 4.0; 95% CI, 1.9-8.3).
According to a multivariate matched analysis, intra-abdominal pathology (OR, 5.9;
95% CI, 2.5-14.1), and >=3 heel punctures (OR, 5.4; 95% CI, 2.4-12.2) remained
independent risk factors for CLABSI. CONCLUSION The presence of an active intra
abdominal pathology increased the risk of CLABSI by almost 6-fold. Similar to
CLABSI in oncology patients, a subgroup of CLABSI with mucosal barrier injury
should be considered for infants in the NICU with active intra-abdominal
pathology. Infect Control Hosp Epidemiol 2016;1446-1452.
PMID- 27609630
TI - A novel simian retrovirus subtype discovered in cynomolgus monkeys (Macaca
fascicularis).
AB - A new simian retrovirus (SRV) subtype was discovered in China and the USA from
Cambodian-origin cynomolgus monkeys. Histopathological examination from
necropsied animals showed multifocal lymphoplasmacystic and histocytic
inflammation. The complete genome sequences demonstrated that the US virus
isolates were nearly identical (99.91-99.93 %) and differed only slightly (99.13
99.16 % identical) from the China isolate. Phylogenetic analysis showed that the
new virus isolates formed a distinct branch of SRV-1 through -7, and therefore
were named this subtype, SRV-8. This SRV-8 variant was also phylogenetically and
serologically more closely related to SRV-4 than any other SRV subtype.
PMID- 27609631
TI - Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV
infected patients between 1993 and 2013: Impact of hepatitis C co-infection.
AB - BACKGROUND: New patterns in epidemiological characteristics of people living with
HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy
(HAART) have changed the profile of hospital admissions in this population. The
aim of this study was to evaluate trends in hospital admissions, re-admissions,
and mortality rates in HIV patients and to analyze the role of HCV co-infection.
METHODS: A retrospective cohort study conducted on all hospital admissions of HIV
patients between 1993 and 2013. The study time was divided in two periods (1993
2002 and 2003-2013) to be compared by conducting a comparative cross-sectional
analysis. RESULTS: A total of 22,901 patient-years were included in the analysis,
with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age
36+/-11 years, 37% HIV/HCV co-infected patients). The median length of hospital
stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A
significant decrease in hospital admissions related with infectious and
psychiatric diseases was observed in the last period (2003-2013), but there was
an increase in those related with malignancies, cardiovascular, gastrointestinal,
and chronic respiratory diseases. In-hospital mortality remained high (6.8% in
the first period vs. 6.3% in the second one), with a progressive increase of non
AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate
significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV
co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to
infectious and psychiatric disorders have decreased, with a significant increase
in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory
diseases. In-hospital mortality is currently still high, but mainly because of
non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re
admissions during the study period.
PMID- 27609632
TI - Pregnancy as an opportunity to diagnose human-immunodeficiency virus immigrant
women in Catalonia.
AB - INTRODUCTION: Mother-to-child transmission (MTCT) is relevant in the global
epidemiology of human-immunodeficiency virus (HIV), as it represents the main
route of infection in children. The study objectives were to determine the rate
of HIV-MTCT and its epidemiological trend between the Spanish-born and immigrant
population in Catalonia in the period 2000-2014. METHODS: A prospective
observational study of mother-child pairs exposed to HIV, treated in 12 hospitals
in Catalonia in the period 2000-2014. HIV-MTCT rate was estimated using a
Bayesian logistic regression model. R and WinBUGS statistical software were used.
RESULTS: The analysis included 909 pregnant women, 1,009 pregnancies, and 1,032
children. Data on maternal origin was obtained in 79.4% of women, of whom 32.7%
were immigrants, with 53.0% of these from sub-Saharan Africa. The overall HIV
MTCT rate was 1.4% (14/1,023; 95% CI; 0.8-2.3). The risk of MTCT-HIV was 10-fold
lower in women with good virological control (P=.01), which was achieved by two
thirds of them. The proportion of immigrants was significantly higher in the
period 2008-2014 (P<.0001), for the HIV-diagnosis (P<.0001), and antiretroviral
administration (P=.02) during pregnancy, and for undetectable viral load next to
delivery (P<.001). There were no differences in the rate of MTCT-HIV among
Spanish-born and immigrant women (P=.6). CONCLUSIONS: There is a gradual increase
in HIV pregnant immigrants in Catalonia. Although most immigrant women were
diagnosed during pregnancy, the rate of MTCT-HIV was no different from the
Spanish-born women.
PMID- 27609628
TI - Genome editing in cardiovascular diseases.
AB - Genome-editing tools, which include zinc finger nucleases (ZFNs), transcription
activator-like effector nucleases (TALENs), and clustered regularly interspaced
short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems, have
emerged as an invaluable technology to achieve somatic and germline genomic
manipulation in cells and model organisms for multiple applications, including
the creation of knockout alleles, introducing desired mutations into genomic DNA,
and inserting novel transgenes. Genome editing is being rapidly adopted into all
fields of biomedical research, including the cardiovascular field, where it has
facilitated a greater understanding of lipid metabolism, electrophysiology,
cardiomyopathies, and other cardiovascular disorders, has helped to create a
wider variety of cellular and animal models, and has opened the door to a new
class of therapies. In this Review, we discuss the applications of genome-editing
technology throughout cardiovascular disease research and the prospect of in vivo
genome-editing therapies in the future. We also describe some of the existing
limitations of genome-editing tools that will need to be addressed if
cardiovascular genome editing is to achieve its full scientific and therapeutic
potential.
PMID- 27609634
TI - Online cardiac output estimation during transvalvular left ventricular
assistance.
AB - BACKGROUND AND OBJECTIVES: Sufficient cardiac output is one of the main goals of
ventricular assist device therapy. To date, there is no adequate method to
estimate the combined amount of blood the native heart and a continuous-flow
assist device pump through the circulatory system. This paper presents an
approach to estimate total cardiac output based on the signals provided by
optical pressure sensors mounted on the inlet and outlet of an Abiomed Impella CP
pump. METHODS: Two Kalman filters were used in parallel for joint estimation of
the aortic flow rate and the hydraulic resistance of the aortic valve. The
filters utilized a third order nonlinear state-space representation of the
cardiovascular system with two nominal parameter sets, one for ovine and another
for human subjects. The accuracy of the estimated cardiac output has been
investigated in a hybrid mock circulatory loop and an animal study involving two
sheep with experimentally induced acute ischaemic heart disease supported by a
transvalvular left ventricular assist device. RESULTS: The in vitro accuracy of
the cardiac output estimation is +/-3.64%. In an ovine model, the comparison of
the estimated cardiac output with an ultrasonic flow measurement in the pulmonary
artery showed 95% limits of agreement of -0.004 +/- 0.897 L min-1. The estimation
errors were comparable to the accuracy of the measurement (+/-10%), which is the
gold standard in research for invasive blood flow diagnostics. CONCLUSIONS: The
online estimation of total cardiac output may give the treating physician a
direct and physiologically meaningful feedback on the pump speed setting. One
promising possible application of our method is physiological control, where the
cardiac output can be used as the control variable for closed-loop ventricular
assist device therapy.
PMID- 27609633
TI - Blocking Modification of Eukaryotic Initiation 5A2 Antagonizes Cervical Carcinoma
via Inhibition of RhoA/ROCK Signal Transduction Pathway.
AB - Cervical carcinoma is one of the leading causes of cancer-related death for
female worldwide. Eukaryotic initiation factor 5A2 belongs to the eukaryotic
initiation factor 5A family and is proposed to be a key factor involved in the
development of diverse cancers. In the current study, a series of in vivo and in
vitro investigations were performed to characterize the role of eukaryotic
initiation factor 5A2 in oncogenesis and metastasis of cervical carcinoma. The
expression status of eukaryotic initiation factor 5A2 in 15 cervical carcinoma
patients was quantified. Then, the effect of eukaryotic initiation factor 5A2
knockdown on in vivo tumorigenicity ability, cell proliferation, cell cycle
distribution, and cell mobility of HeLa cells was measured. To uncover the
mechanism driving the function of eukaryotic initiation factor 5A2 in cervical
carcinoma, expression of members within RhoA/ROCK pathway was detected, and the
results were further verified with an RhoA overexpression modification. The level
of eukaryotic initiation factor 5A2 in cervical carcinoma samples was
significantly higher than that in paired paratumor tissues ( P < .05). And the in
vivo tumorigenic ability of HeLa cells was reduced by inhibition of eukaryotic
initiation factor 5A2. Knockdown of eukaryotic initiation factor 5A2 in HeLa
cells decreased the cell viability compared with normal cells and induced G1
phase cell cycle arrest ( P < .05). Moreover, the cell migration ability of
eukaryotic initiation factor 5A2 knockdown cells was dramatically inhibited.
Associated with alterations in phenotypes, RhoA, ROCK I, and ROCK II were
downregulated. The above-mentioned changes in eukaryotic initiation factor 5A2
knockdown cells were alleviated by the overexpression of RhoA. The major findings
outlined in the current study confirmed the potential of eukaryotic initiation
factor 5A2 as a promising prognosis predictor and therapeutic target for cervical
carcinoma treatment. Also, our data inferred that eukaryotic initiation factor
5A2 might function in carcinogenesis of cervical carcinoma through an RhoA/ROCK
dependent manner.
PMID- 27609635
TI - DNA sequencing confirms PCR-RFLP identification of wild caught Larroussius sand
flies from Crete and Cyprus.
AB - Many Phlebotomine sand fly species (Diptera, Psychodidae) are vectors of the
protozoan parasite Leishmania causing a group of diseases called the
leishmaniases. The subgenus Larroussius includes sand fly vectors found in South
East Mediterranean Basin responsible for Visceral (VL) and Cutaneous human
leishmaniasis (CL). It is important to monitor these medically important insects
in order to safely predict possible Leishmania transmission cycles. Leishmania
infantum is endemic in the islands of Crete and Cyprus with increasing VL cases
in humans and dogs and in Cyprus the newly introduced Leishmania donovani causes
both VL and CL in humans. The morphological identification of the females of the
subgenus Larroussius often presents difficulties. Morphology and COI PCR - RFLP
were used to identify wild caught Larroussius sand flies belonging to Phlebotomus
tobbi, P. perfiliewi, and P. neglectus species from Crete and Cyprus. The
identification results were further confirmed by sequencing (DNA barcoding) and
Bayesian phylogenetic analysis. COI PCR - RFLP, when correctly optimized and with
respect to geographical origin, can serve as an initial patterning identification
tool when large sand fly numbers need to be identified. It could accurately
assign Larroussius females and males to their taxa overcoming the difficulties of
morphological identification. Finally, DNA barcoding will contribute to a
molecular identification database to be used for in-depth species studies.
PMID- 27609636
TI - Acanthamoeba castellanii: A new high-throughput method for drug screening in
vitro.
AB - Despite significant public health impact, there is no specific antiprotozoal
therapy for prevention and treatment of Acanthamoeba castellanii infection. There
is a need for new and efficient anti-Acanthamoeba drugs that are less toxic and
can reduce treatment duration and frequency of administration. In this context a
new, rapid and sensitive assay is required for high-throughput activity testing
and screening of new therapeutic compounds. A colorimetric assay based on
sulforhodamine B (SRB) staining has been developed for anti-Acanthamoeba drug
susceptibility testing and adapted to a 96-well microtiter plate format. Under
these conditions chlorhexidine was tested to validate the assay using two
clinical strains of A. castellanii (Neff strain, T4 genotype [IC50 4.68+/-0.6MUM]
and T3 genotype [IC50 5.69+/-0.9MUM]). These results were in good agreement with
those obtained by the conventional Alamar Blue assay, OCR cytotoxicity assay and
manual cell counting method. Our new assay offers an inexpensive and reliable
method, which complements current assays by enhancing high-throughput anti
Acanthamoeba drug screening capabilities.
PMID- 27609637
TI - Mitochondrial COI gene as a tool in the taxonomy of mosquitoes Culex subgenus
Melanoconion.
AB - The subgenus Melanoconion is the second largest subgenus within the genus Culex,
with 160 described species. Several of the species are proven vectors of
arboviruses, including West Nile virus, Venezuelan equine encephalitis virus
complex and Eastern equine encephalomyelitis virus. Species of Melanoconion are
well distributed from southern North America to most countries of South America
and display the highest species diversity in tropical regions. Taxonomical
identification within this group has been primarily based on morphological
characters, with the male genitalia as the source of the most solid diagnostic
features. The difficulty in reaching accurate species determinations when
studying specimens of Culex (Melanoconion) has been extensively documented as a
real limitation to expand knowledge of these insects. We tested the utility of
the mitochondrial gene COI as a complementary tool in the taxonomy of
Melanoconion. Using a data set of 120 COI sequences from Culex specimen captured
in several localities in Brazil, the utility of COI barcodes for species
delimitation is discussed through the evaluation of genetic divergences among
specimens and the clustering patterns of species in three topologies obtained
with Neighbor Joining, Maximum Likelihood and Bayesian phylogenetic inference.
For all specimens included in this study a previous morphological examination was
performed, and most of the taxonomical determinations were corroborated using the
COI barcode. We generated COI sequences that belong to 48 species of
Melanoconion, with a mean intraspecific K2P genetic divergence of 3%; and all
interspecific divergence values higher than the intraspecific divergence values.
This is the first comprehensive study of subgenus Melanoconion, with evidence of
COI as a useful and accessible DNA barcode.
PMID- 27609638
TI - A sound trap for Aedes albopictus (Skuse) male surveillance:Response analysis to
acoustic and visual stimuli.
AB - Aedes albopictus (Skuse) is one of the most invasive mosquito species capable of
transmitting various harmful pathogens to humans. Failure of vector control
strategies against this species requires the development of new effective vector
control methods. Among the alternative genetic control measures under
development, the sterile insect technique (SIT) is today receiving a renewed
interest as a possible effective tool to be integrated in an area-wide pest
management approach. The monitoring of the abundance, distribution, movements and
ratio of released sterile and wild fertile males is a fundamental requirement for
the successful management of any pest control activities integrating an SIT
component. Although several traps exist for adult female mosquito surveillance
and population control, effective methods to monitor large quantities of non
biting males were less researched in the past and more difficult to obtain. In
this study we analyzed the response of A. albopictus males to various sound
stimuli produced with different volumes and frequencies in association with
visual cues for the optimization of male catches. The production of modulated
frequencies continuously varying within the typical female sound emission range
(500-650Hz) showed the best results for a sound pressure level between 75 and
79dB measured at the speaker level. The black color of the trap, however, seems
decisive to attract males in the vicinity of sound traps and the combined effect
produced by these stimuli is additive. We also observed that males increase their
response to acoustic stimulation up to 4days of age and then show a continuous
and progressive decline of their sound responsiveness. A plastic sound trap
prototype capable of producing the most effective sound stimuli tested at
laboratory conditions showed a good A. albopictus males' attractiveness in the
field despite a reduced use of color stimuli. The use of sound stimuli therefore
appears to be a promising prospect to increase the capture rate of A. albopictus
males in new or in already existing mosquito traps.
PMID- 27609639
TI - Dengue virus surveillance: Detection of DENV-4 in the city of Sao Jose do Rio
Preto, SP, Brazil.
AB - Dengue viruses are the most common arbovirus infection worldwide and are caused
by four distinct serotypes of the dengue virus (DENV). In the present study, we
assessed DENV transmission in Sao Jose do Rio Preto (SJRP) from 2010 to 2014. We
analyzed blood samples from febrile patients who were attended at health care
centers in SJRP. DENV detection was performed using multiplex RT-PCR, using
flavivirus generic primers, based on the genes of the non-structural protein
(NS5), followed by nested-PCR assay with species-specific primers. We analyzed
1549 samples, of which 1389 were positive for NS1 by rapid test. One thousand and
eight-seven samples (78%) were confirmed as positive by multiplex RT-PCR: DENV-4,
48.5% (528/1087); DENV-1, 41.5% (449/1087); DENV-2, 9.5% (104/1087); and co
infection (5 DENV-1/DENV-4, 1 DENV-1/DENV-2), 0.5% (6/1087). Phylogenetic
analysis of the DENV-4 grouped the isolates identified in this study with the
American genotype and the showed a relationship between isolates from SJRP and
isolates from the northern region of South America. Taken together, our data
shows the detection and emergence of new dengue genotype in a new region and
reiterate the importance of surveillance programs to detect and trace the
evolution of DENV.
PMID- 27609641
TI - Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to
Renal Cell Carcinoma.
AB - In most cases, cytotoxic drugs do not preferentially accumulate at the tumor
site, causing unwanted toxicities and preventing dose escalation to
therapeutically active regimens. Here, we show that acetazolamide derivatives,
which bind to carbonic anhydrase IX (CAIX) on the surface of kidney cancer cells,
selectively deliver payloads at the site of disease, sparing normal organs.
Biodistribution studies, performed in tumor-bearing mice with acetazolamide
derivatives bearing a technetium-99m chelator complex or a red fluorophore as
payload, revealed a preferential tumor accumulation of the compound at doses up
to 560 nmol/kg. The percentage of injected dose per gram in the tumor was dose
dependent and revealed optimal tumor:organ ratios at 140 nmol/kg, with a
tumor:blood ratio of 80:1 at 6 hours. Acetazolamide, coupled to potent cytotoxic
drugs via a dipeptide linker, exhibited a potent antitumor activity in nude mice
bearing SKRC-52 renal cell carcinomas, whereas drug derivatives devoid of the
acetazolamide moiety did not exhibit any detectable anticancer activity at the
same doses. The observation of tumor regression with a noninternalizing ligand
and with different cytotoxic moieties (MMAE and PNU-159682) indicates a general
mechanism of action, based on the selective accumulation of the product on tumor
cells, followed by the extracellular proteolytic release of the cytotoxic payload
at the neoplastic site and the subsequent drug internalization into tumor cells.
Acetazolamide-based drug conjugates may represent a promising class of targeted
agents for the treatment of metastatic kidney cancer, as the majority of human
clear cell renal cell carcinomas are strongly positive for CAIX. Mol Cancer Ther;
15(12); 2926-35. (c)2016 AACR.
PMID- 27609640
TI - Rigid Cooperation of Per1 and Per2 proteins.
AB - Period circadian clock (Per) genes Per1 and Per2 have essential roles in
circadian oscillation. In this study, we identified a new role of Per1-Per2
cooperation, and its mechanism, using our new experimental methods. Under
constant light conditions, the period length of Per1 and Per2 knockout mice
depended on the copy number ratio of Per1:Per2. We then established a light
emitting diode-based lighting system that can generate any pattern of light
intensity. Under gradually changing light in the absence of phase shift with
different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a
broader range of period length than wild-type mice. To analyse Per1-Per2
cooperative roles at the cell culture level, we established a Per2 knockout
rescue system, which can detect period shortening in a familial advanced sleep
phase syndrome (FASPS) mutant. Upon introduction of the Per1 coding region in
this system, we saw period shortening. In conclusion, short period-associated
protein Per1 and long period-associated Per2 cooperated to rigidly confine the
circadian period to "circa" 24-h. These results suggest that the rigid circadian
rhythm maintained through the cooperation of Per1-Per2 could negatively impact
modern society, in which the use of artificial lighting is ubiquitous, and result
in circadian disorders, including delirium.
PMID- 27609642
TI - Aged neutrophils contribute to the first line of defense in the acute
inflammatory response.
AB - Under steady-state conditions, aged neutrophils are removed from the circulation
in bone marrow, liver, and spleen, thereby maintaining myeloid cell homeostasis.
The fate of these aged immune cells under inflammatory conditions, however,
remains largely obscure. Here, we demonstrate that in the acute inflammatory
response during endotoxemia, aged neutrophils cease returning to the bone marrow
and instead rapidly migrate to the site of inflammation. Having arrived in
inflamed tissue, aged neutrophils were found to exhibit a higher phagocytic
activity as compared with the subsequently recruited nonaged neutrophils. This
distinct behavior of aged neutrophils under inflammatory conditions is dependent
on specific age-related changes in their molecular repertoire that enable these
"experienced" immune cells to instantly translate inflammatory signals into
immune responses. In particular, aged neutrophils engage Toll-like receptor-4-
and p38 MAPK-dependent pathways to induce conformational changes in beta2
integrins that allow these phagocytes to effectively accomplish their mission in
the front line of the inflammatory response. Hence, ageing in the circulation
might represent a critical process for neutrophils that enables these immune
cells to properly unfold their functional properties for host defense.
PMID- 27609644
TI - Chronic social defeat stress leads to changes of behaviour and memory-associated
proteins of young mice.
AB - It is well known that social defeat stress can induce depressive behaviours and
cognitive impairment. However, the molecular mechanism by which only a minority
of stress-exposed individuals are affected is not clear. In this study, thirty 3
week-old male c57BL/6 mice were exposed to 30 days of social defeat stress,
following which susceptible (socially avoidant) and unsusceptible (socially
interactive) mice were identified using social investigation. Twenty-four hours
after the last episode of defeat, separate groups of mice were tested in the
sucrose preference, open field, elevated plus-maze and Morris water maze
behavioural assays. Also, the levels of memory-associated proteins in the
hippocampus were examined, including postsynaptic density 95 (PSD95),
postsynaptic density 93 (PSD93), and Protein kinase A (PKA). The levels of PSD95,
PSD93, and PKA were significantly lower in susceptible mice. We also found that
the upstream regulatory factor of these proteins, phosphorylated Camp-Responsive
Element-Binding Protein (CREB), was reduced after social defeat in the
susceptible group only, while the level of histone deacetylase 6 (HDAC6) was
significantly elevated. These data suggest that memory-associated proteins and
phosphorylated CREB may play important roles in memory impairment and behavioural
responses to chronic stress.
PMID- 27609643
TI - Platelet WDR1 suppresses platelet activity and is associated with cardiovascular
disease.
AB - Platelet activity plays a major role in hemostasis with increased platelet
activity likely contributing to the pathogenesis of atherothrombosis. We sought
to identify associations between platelet activity variability and platelet
related genes in healthy controls. Transcriptional profiling of platelets
revealed that WD-40 repeat domain 1 (WDR1), an enhancer of actin-depolymerizing
factor activity, is downregulated in platelet messenger RNA (mRNA) from subjects
with a hyperreactive platelet phenotype. We used the human megakaryoblastic cell
line MEG-01 as an in vitro model for human megakaryocytes and platelets.
Stimulation of MEG-01 with thrombin reduced levels of WDR1 transcripts and
protein. WDR1 knockdown (KD) in MEG-01 cells increased adhesion and spreading in
both the basal and activated states, increased F-actin content, and increased the
basal intracellular calcium concentration. Platelet-like particles (PLPs)
produced by WDR1 KD cells were fewer in number but larger than PLPs produced from
unmodified MEG-01 cells, and had significantly increased adhesion in the basal
state and upon thrombin activation. In contrast, WDR1 overexpression reversed the
WDR1 KD phenotype of megakaryocytes and PLPs. To translate the clinical
significance of these findings, WDR1 expression was measured in platelet RNA from
subjects with established cardiovascular disease (n = 27) and age- and sex
matched controls (n = 10). The WDR1 mRNA and protein level was significantly
lower in subjects with cardiovascular disease. These data suggest that WDR1 plays
an important role in suppressing platelet activity, where it alters the actin
cytoskeleton dynamics, and downregulation of WDR1 may contribute to the platelet
mediated pathogenesis of cardiovascular disease.
PMID- 27609646
TI - Slope climbing challenges, fear of heights, anxiety and time of the day.
AB - When exposed to an unfamiliar open space, animals experience fear and attempt to
find an escape route. Anxiety emerges when animals are confronted with a
challenging obstacle to this fear motivated escape. High anxiety animals do not
take risks; they avoid the challenge. The present experiments investigated this
risk avoidant behavior in mice. In experiment 1, BALB/c, C57BL/6J and CD-1 mice
were exposed to a large platform with downward inclined steep slopes attached on
two opposite sides. The platform was elevated 75 and 100cm from the ground, in a
standard (SPDS) and in a raised (RPDS) configuration, respectively. In experiment
2, the platform was elevated 75cm from the ground. Mice had to climb onto a stand
at the top of upward inclined slopes (SPUS). In experiment 3, BALB/c mice were
exposed to SPDS with steep or shallow slopes either in early morning or in late
afternoon. In all 3 test configurations, mice spent more time in the areas
adjacent to the slopes than in the areas adjacent to void, however only C57BL/6J
and CD-1 crossed onto the slopes in SPDS, and crossed onto the stands in SPUS
whereas BALB/c remained on the platform in SPDS and explored the slopes in SPUS.
Elevation of the platform from the ground reduced the crossings onto the slopes
in C57BL/6J and CD-1, and no differences were observed between BALB/c and
C57BL/6J. BALB/c mice demonstrated no difference in anxiety when tested early
morning or late afternoon; they crossed onto shallow slopes and avoided the steep
one.
PMID- 27609647
TI - Impaired perception of human movements in Parkinson's disease.
AB - Interacting with other individuals in a social world requires fast and accurate
perception of other individuals' identity, actions, or intentions. Humans are
very efficient in these social tasks, as they can extract social information even
if the actor is represented only by a handful of point-lights on an otherwise
invisible body. Theories have argued that efficient visual perception of actions
is based on intact motor system functioning. The motor system provides visuo
motor action representations shaped by the observer's own movements or motor
repertoire. If the observer's motor repertoire is impaired, this should lead to
impaired visuo-motor representations and ultimately to impaired visual perception
of movements. Here we tested this hypothesis in a behavioral study with patients
suffering from Parkinson's disease (PD). PD patients are typically impaired in
movement execution. We tested these patients and a matched control group in a
visual discrimination task on human movement perception. The results showed that
PD patients were significantly impaired in the perception of human movements.
This impairment was most prominent for transitive (object-related) movements. The
results indicate that impaired movement execution critically influences movement
perception. The results support the hypothesis that the motor system plays a
causal role for the visual perception of human movements.
PMID- 27609645
TI - ChAT-positive neurons participate in subventricular zone neurogenesis after
middle cerebral artery occlusion in mice.
AB - The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are
unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as
well as neurotransmitters, have been shown to play important roles in SVZ
neurogenesis. Recently, a previously unknown population of choline
acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have
direct control over neural stem cell proliferation by indirectly activating
fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal
control over SVZ neurogenesis. In this study, we assessed whether these ChAT+
neurons also participate in stroke-induced neurogenesis. We used a permanent
middle cerebral artery occlusion (MCAO) model produced by transcranial
electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR]
antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the
role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs,
phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were
upregulated in mice on day 7 after MCAO. MCAO also significantly increased the
number of BrdU/doublecortin-positive cells and protein levels of phosphorylated
neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was
activated in the SVZ, and doublecortin-positive cells increased in the peri
infarction region. These post-stroke neurogenic effects were enhanced by
donepezil and partially decreased by atropine. Neither atropine nor donepezil
affected peri-infarct microglial activation or serum concentrations of TNF-alpha,
IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the
SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism
for neurogenesis after stroke.
PMID- 27609648
TI - Differential activation of vasotocin neurons in contexts that elicit aggression
and courtship.
AB - Despite continued study on the neurobiological bases of aggressive and sexual
behaviors, it is still not well understood how the brain integrates social
information with physiological and neural states to produce context-specific
behavioral outcomes. In fishes, manipulation of endogenous levels of arginine
vasotocin (AVT) through peripheral and intracerebroventricular pharmacological
injections results in significant changes in social behaviors, including
aggressive and reproduction-related behaviors. In addition, many features of AVT
neurons have been shown to correlate with social status and associated behavioral
phenotypes. In this study, we used the immediate early gene egr-1 as a marker for
neuronal activity and quantified the number of AVT neurons that were positive for
egr-1 mRNA by in situ hybridization in Astatotilapia burtoni males that were
exposed to either a social context that would elicit aggression or to one that
would elicit courtship. In these social settings, focal males readily displayed
context- appropriate bouts of aggression (towards the opponent) or bouts of
courting (towards females). We found that males that fought had higher levels of
egr-1 expression in the preoptic area compared to courting males. A greater
proportion of AVT cells was positive for egr-1 after a fight than after a bout of
courting. We mapped mRNA distribution of AVT V1a receptor subtypes v1a1 and v1a2
in the brain and identified overlapping areas of expression in nuclei in the
ventral telencephalon, hypothalamus and thalamus as key areas for AVT signaling
in males.
PMID- 27609649
TI - Provision of fascia iliaca compartment block in the acute management of proximal
femoral fractures: A national observational study of UK hospitals.
AB - AIMS: Fascia iliaca compartment block (FICB) is a simple regional anaesthetic
block that has been shown to be superior to other regional anaesthetic blocks
with regards to success rate and analgesic efficacy in the acute management of
proximal femoral fractures. The objective was to quantitatively assess the
provision of FICB for patients with proximal femoral fractures in the UK.
METHODS: A national observational study of all acute medical trusts in the UK
(n=187) was conducted. Each trust was contacted and asked to complete a freedom
of information request relating to the use of regional nerve blocks in patients
with a proximal femoral fracture between 2/11/2014 and 2/11/2015. The STROBE
checklist was used to help design and conduct the study. RESULTS: 144/187(77.0%)
of medical trusts across the UK responded. Overall, 61.8% of trusts routinely
performed FICB for patients with a neck of femur (NOF) fracture. The number of
trusts with a specific standardised proforma for NOF fracture patients was
127/144 (88.2%), while 83/144 (57.6%) included a section relating to FICB. 50/144
(34.7%) of trusts had no hospital related guideline for FICBs in NOF fracture
patients. The use of analgesia in NOF fracture patients was audited in 95/144
(66.0%) of trusts. Where FICB was administered, the procedure was typically
conducted by specialists in emergency medicine (50.6%), anaesthetics (34.6%) and
orthopaedics (14.8%). Common reasons for lack of FICB provision include: lack of
trained staff, resumption of adequate analgesia via other methods and a
perception that there is insufficient evidence for routine use of peripheral
nerve blocks improving survival and outcomes. CONCLUSIONS: Administration of
regional nerve blocks for patients with proximal femoral fractures is increasing
but variable between trusts. Further work should examine how barriers to the
delivery of FICBs might be addressed.
PMID- 27609650
TI - The surgical management of facial trauma in British soldiers during combat
operations in Afghanistan.
AB - INTRODUCTION: The recent Afghanistan conflict caused a higher proportion of
casualties with facial injuries due to both the increasing effectiveness of
combat body armour and the insurgent use of the improvised explosive device
(IED). The aim of this study was to describe all injuries to the face sustained
by UK service personnel from blast or gunshot wounds during the highest intensity
period of combat operations in Afghanistan. METHODS: Hospital records and Joint
Theatre Trauma Registry data were collected for all UK service personnel killed
or wounded by blast and gunshot wounds in Afghanistan between 01 April 2006 and
01 March 2013. RESULTS: 566 casualties were identified, 504 from blast and 52
from gunshot injuries. 75% of blast injury casualties survived and the IED was
the most common mechanism of injury with the mid-face the most commonly affected
facial region. In blast injuries a facial fracture was a significant marker for
increased total injury severity score. A facial gunshot wound was fatal in 53% of
cases. The majority of survivors required a single surgical procedure for the
facial injury but further reconstruction was required in 156 of the 375 of
survivors aero medically evacuated to the UK. CONCLUSIONS: The presence and
pattern of facial fractures was significantly different in survivors and
fatalities, which may reflect the power of the blast that these cohorts were
exposed to. The Anatomical Injury Scoring of the Injury Severity Scale was
inadequate for determining the extent of soft tissue facial injuries and did not
predict morbidity of the injury.
PMID- 27609651
TI - Sacroiliac joint asymmetry in paediatric computed tomography.
PMID- 27609652
TI - Fluorescence excitation-emission matrix spectroscopy analysis of landfill
leachate DOM in coagulation-flocculation process.
AB - Landfill leachate contains a variety of organic matters, some of which can be
excited and emit fluorescence signal. In order to degrade these organic matters,
the pretreatment of the leachate is needed, which can improve the degradation
performance of post-treatment process. Coagulation-flocculation is one of the
important pretreatment processes to treat landfill leachate. Assessing the
chemical compositions of landfill leachate is helpful in the understanding of
their sources and fates as well as the mechanistic behaviors in the water
environment. The present work aimed to use fluorescence excitation-emission
matrix spectroscopy (EEMs) to characterize the chemical fractions of landfill
leachate dissolved organic matter (DOM) in conjunction with parallel factor
analysis (PARAFAC). Results showed that the DOM of landfill leachate tested in
this study was identified resulting from microbial input, which included five
typical characteristic peaks and four kinds of PARAFAC fractions. These fractions
were mainly composed of hydrophobic macromolecule humic acid-like (HM-HA),
hydrophilic intermediate molecular fulvic acid-like (HIM-FA), and hydrophilic
small molecule protein-like substances (HSM-PS). HM-HA and HIM-FA were found to
be easier to remove than HSM-PS. Further research on HSM-PS removal by
coagulation-flocculation still needs to be improved.
PMID- 27609653
TI - Novel baseline predictors of adverse events during oral immunotherapy in children
with peanut allergy.
AB - BACKGROUND: Though peanut oral immunotherapy (OIT) is a promising investigational
therapy, its potential is limited by substantial adverse events (AEs), which are
relatively understudied. OBJECTIVE: A retrospective analysis was conducted,
pooling data from 3 pediatric peanut OIT trials, comprising the largest analysis
of peanut OIT safety to date. METHODS: We pooled data from 104 children with
peanut allergy from 3 peanut OIT studies. We catalogued AEs from parental
reports, daily symptom diaries, and dose escalations. We included events that
were considered likely related to OIT and identified potential baseline
predictors of higher AE rates using generalized linear regression models.
RESULTS: Eighty percent of subjects experienced likely related AEs during OIT
(72% during buildup and 47% during maintenance). Of these AEs, over 90% occurred
while at home. Approximately 42% of subjects experienced systemic reactions, and
49% experienced gastrointestinal symptoms. Twenty percent of subjects dropped
out, with half (10% of the overall group) due to persistent gastrointestinal
symptoms. Baseline allergic rhinitis (AR) and peanut SPT wheal size were
significant predictors of higher overall AE rates. SPT wheal size predicted
increased gastrointestinal AEs, and AR predicted increased systemic reactions.
Over the course of OIT, 61% of subjects received treatment for likely related
AEs, 59% with antihistamines and 12% with epinephrine. CONCLUSIONS: Peanut OIT is
associated with frequent AEs, with rates declining over time, and most graded
mild. However, systemic reactions and intolerable gastrointestinal AEs do occur
and are significantly associated with AR and peanut SPT wheal size, respectively.
Further study is needed of predictive biomarkers and the overall risks and
benefits of OIT.
PMID- 27609654
TI - Heterozygosity for transmembrane activator and calcium modulator ligand
interactor A144E causes haploinsufficiency and pneumococcal susceptibility in
mice.
AB - BACKGROUND: The B-cell receptor transmembrane activator and calcium modulator
ligand interactor (TACI) is important for T-independent antibody responses. One
in 200 blood donors are heterozygous for the TACI A181E mutation. OBJECTIVE: We
sought to investigate the effect on B-cell function of TACI A181E heterozygosity
in reportedly healthy subjects and of the corresponding TACI A144E mutation in
mice. METHODS: Nuclear factor kappaB (NF-kappaB) activation was measured by using
the luciferase assay in 293T cells cotransfected with wild-type and mutant TACI.
TACI-driven proliferation, isotype switching, and antibody responses were
measured in B cells from heterozygous TACI A144E knock-in mice. Mouse mortality
was monitored after intranasal pneumococcal challenge. RESULTS: Levels of natural
antibodies to the pneumococcal polysaccharide component phosphocholine were
significantly lower in A181E-heterozygous than TACI-sufficient Swedish blood
donors never immunized with pneumococcal antigens. Although overexpressed hTACI
A181E and mTACI A144E acted as dominant-negative mutations in transfectants,
homozygosity for A144E in mice resulted in absent TACI expression in B cells,
indicating that the mutant protein is unstable when naturally expressed. A144E
heterozygous mice, such as TACI+/- mice, expressed half the normal level of TACI
on their B cells and exhibited similar defects in a proliferation-inducing ligand
driven B-cell activation, antibody responses to TNP-Ficoll, production of natural
antibodies to phosphocholine, and survival after intranasal pneumococcal
challenge. CONCLUSION: These results suggest that TACI A181E heterozygosity
results in TACI haploinsufficiency with increased susceptibility to pneumococcal
infection. This has important implications for asymptomatic TACI A181E carriers.
PMID- 27609655
TI - Estimated disease incidence of RAG1/2 mutations: A case report and querying the
Exome Aggregation Consortium.
PMID- 27609656
TI - Effectiveness of bronchial thermoplasty in patients with severe refractory
asthma: Clinical and histopathologic correlations.
AB - BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in
patients with severe asthma, yet its effect on different bronchial structures
remains unknown. OBJECTIVE: We sought to examine the effect of BT on bronchial
structures and to explore the association with clinical outcome in patients with
severe refractory asthma. METHODS: Bronchial biopsy specimens (n = 300) were
collected from 15 patients with severe uncontrolled asthma before and 3 months
after BT. Immunostained sections were assessed for airway smooth muscle (ASM)
area, subepithelial basement membrane thickness, nerve fibers, and epithelial
neuroendocrine cells. Histopathologic findings were correlated with clinical
parameters. RESULTS: BT significantly improved asthma control and quality of life
at both 3 and 12 months and decreased the numbers of severe exacerbations and the
dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied
by a reduction in ASM area (median values before and after BT, respectively:
19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th
IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4
MUm [25th-75th IQR, 4.0-4.7 MUm] and 3.9 MUm [25th-75th IQR, 3.7-4.6 MUm], P =
0.02), submucosal nerves (1.0 0/00 [25th-75th IQR, 0.7-1.3 0/00] immunoreactivity
and 0.3 0/00 [25th-75th IQR, 0.1-0.5 0/00] immunoreactivity, P < .001), ASM
associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per
mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02),
and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and
0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were
associated based on Asthma Control Test scores, numbers of exacerbations, and
visits to the emergency department (all P <= .02) 3 and 12 months after BT.
CONCLUSION: BT is a treatment option in patients with severe therapy-refractory
asthma that downregulates selectively structural abnormalities involved in airway
narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial
cells, and bronchial nerve endings.
PMID- 27609657
TI - Assessment of wheezing frequency and viral etiology on childhood and adolescent
asthma risk.
PMID- 27609660
TI - The effect of morbid obesity on morphine glucuronidation.
AB - The purpose of the present work was to study the change in morphine metabolic
ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to
identify clinical and/or biological factors associated with this change. The
pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and
morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean
BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean
BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmax and AUC0-inf were significantly
increased and morphine Tmax significantly shortened at 6 months after RYGB
compared with preoperative data, indicating an important increase in the rate and
extent of morphine absorption. The morphine metabolic ratio 0-inf
M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months
postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not
in the immediate post-operative period. The change in morphine metabolic ratio
was associated with a change in BMI, fat mass in kg, and triglyceride levels
(rho=0.5, p<=0.04). The degree of change in several markers of low-grade
inflammation, or the level of liver steatosis and fibrosis before surgery, was
not associated with the change in morphine metabolic ratios. Our findings
indicate that RYGB-induced weight loss significantly decreases morphine metabolic
ratio, arguing for an effect of morbid obesity on glucuronidation. With
glucuronide exposure at 6 months similar to preoperative values, a higher
morphine AUC0-inf should encourage reducing morphine dosage in patients
undergoing RYGB and chronically receiving immediate-release oral morphine.
PMID- 27609658
TI - Omalizumab facilitates rapid oral desensitization for peanut allergy.
AB - BACKGROUND: Peanut oral immunotherapy is a promising approach to peanut allergy,
but reactions are frequent, and some patients cannot be desensitized. The anti
IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might
allow more rapid peanut updosing and decrease reactions. OBJECTIVE: We sought to
evaluate whether omalizumab facilitated rapid peanut desensitization in highly
allergic patients. METHODS: Thirty-seven subjects were randomized to omalizumab
(n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a
rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly
increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued
on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of
peanut protein 12 weeks after stopping study drug. If tolerated, subjects
continued on 4000 mg of peanut protein daily. RESULTS: The median peanut dose
tolerated on the initial desensitization day was 250 mg for omalizumab-treated
subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29
subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks
after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty
three subjects receiving omalizumab versus 1 subject receiving placebo passed the
4000-mg food challenge. Overall reaction rates were not significantly lower in
omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15),
although omalizumab-treated subjects were exposed to much higher peanut doses.
CONCLUSION: Omalizumab allows subjects with peanut allergy to be rapidly
desensitized over as little as 8 weeks of peanut oral immunotherapy. In the
majority of subjects, this desensitization is sustained after omalizumab is
discontinued. Additional studies will help clarify which patients would benefit
most from this approach.
PMID- 27609659
TI - Skin microbiome before development of atopic dermatitis: Early colonization with
commensal staphylococci at 2 months is associated with a lower risk of atopic
dermatitis at 1 year.
AB - BACKGROUND: Disease flares of established atopic dermatitis (AD) are generally
associated with a low-diversity skin microbiota and Staphylococcus aureus
dominance. The temporal transition of the skin microbiome between early infancy
and the dysbiosis of established AD is unknown. METHODS: We randomly selected 50
children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact
Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort
for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites
relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We
identified 10 infants with AD and compared them with 10 randomly selected control
infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and
analysis directly from clinical samples. RESULTS: Bacterial community structures
and diversity shifted over time, suggesting that age strongly affects the skin
microbiome in infants. Unlike established AD, these patients with infantile AD
did not have noticeably dysbiotic communities before or with disease and were not
colonized by S aureus. In comparing patients and control subjects, infants who
had affected skin at month 12 had statistically significant differences in
bacterial communities on the antecubital fossa at month 2 compared with infants
who were unaffected at month 12. In particular, commensal staphylococci were
significantly less abundant in infants affected at month 12, suggesting that this
genus might protect against the later development of AD. CONCLUSIONS: This study
suggests that 12-month-old infants with AD were not colonized with S aureus
before having AD. Additional studies are needed to confirm whether colonization
with commensal staphylococci modulates skin immunity and attenuates development
of AD.
PMID- 27609661
TI - Influence of demographics on clinical outcome of dengue: a cross-sectional study
of 6703 confirmed cases in Vitoria, Espirito Santo State, Brazil.
AB - Dengue presents a wide clinical spectrum of signs and symptoms, with
characteristics of the host potentially influencing the disease evolution.
Therefore, the purpose of this study was to evaluate the influence of gender and
age on dengue clinical outcomes in a recent outbreak situation in Brazil,
applying a cross-sectional design and including 6703 dengue cases with laboratory
confirmation, occurring in Vitoria, Espirito Santo State, Brazil, between 2007
and 2013. Data were obtained from the Information System for Notifiable Diseases.
Overall, 11.3% of the sample presented with severe dengue, which affected 13.0%
of males, 10.0% of females, 8.8% of children, 12.5% of adolescents, 10.5% of
adults and 15.5% of the elderly. Age was higher in the severe dengue group (P =
0.03). Severe dengue was associated with males and the elderly (P < 0.01);
however, considering only severe cases, children presented haemorrhage and plasma
leakage more frequently than older age groups. The results emphasize the
importance of a differentiated protocol for management of dengue cases, taking
into consideration host factors like age. These findings also suggest the elderly
and children as priority groups for immunization in a future implementation of a
vaccine.
PMID- 27609662
TI - Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of
ocular inflammation in rat model.
AB - The therapeutic efficacy of rapamycin conjugated monomethoxy poly(ethylene
glycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelles (rapamycin micelles) was
evaluated in a rat experimental autoimmune uveitis (EAU) model. Rapamycin
micelles exhibited spherical morphology and had a mean particle size of 40nm and
a zeta-potential of -0.89mv. The water solubility of rapamycin improved by more
than 1000-fold in a micellar formulation. Intravitreal injection of MPEG-PCL
micelles did not result in vitreous hemorrhage or retinal detachment.
Fluorescence microscopy demonstrated that labeled micelles localized to the
retinal pigment epithelium for at least 14 days following injection and the drug
concentration of rapamycin micelles in the retinal tissue was significantly
higher than unconjugated rapamycin over this period. At the optimal concentration
of rapamycin micelles (9MUg/eye), clinical signs of EAU were abolished via the
downregulation of the Th1 and Th17 response. There were no significant difference
in T cell proliferation and delayed-type hypersensitivity between the treatment
and control groups, suggesting that the therapeutic effect of rapamycin
manifested locally in the eye and not systemically. These results indicate that
intravitreal injection of rapamycin micelles is a promising therapy for
controlling sterile intraocular inflammation.
PMID- 27609663
TI - Rapid determination of drug solubilization versus supersaturation in natural and
digested lipids.
AB - Lipid-based formulations (LBFs) represent one of the successful formulation
approaches that enable oral delivery of poorly water-soluble drugs. This work
presents a simple equilibrium approach based on solubility in lipids and their
corresponding digestion media to estimate a maximum drug supersaturation ratio
(SRmax). This value of drug concentration normalized by the solubility in the
aqueous digestion phase indicates the propensity for drug precipitation. A set of
16 structurally diverse drugs was first measured for their solubility in
tricaprin and tricaprylin and results were compared to an empirical model based
on molecular predictors. In the next step, digestion media were either prepared
by in vitro lipolysis or by assembling a composition to mimic the endpoint of
digestion. It was found that drug solubility in the pure lipids mainly was
related to the melting point in that increased values resulted in reduced
solubility. The solubility values measured in the lipolysis media correlated well
with those obtained from assembled digestion media. Interestingly, the
solubilization upon digestion was typically higher when using tricaprin than
tricaprylin in spite of that the latter oil (as pure excipient) generally was a
more potent solvent. This work suggests that a simplified digestion screen can be
used to facilitate evaluation of formulations during early development.
Estimation of SRmax provides an early risk assessment of drug precipitation for
LBFs. The method is easily scaled down to the microtiter plate format and can be
used for selecting candidate formulations that merit further evaluation in more
complex and dynamic in vitro tests.
PMID- 27609665
TI - Ocular vestibular evoked myogenic potential testing for the prognosis of Bell's
palsy.
AB - CONCLUSION: oVEMP could be a useful tool for predicting the prognosis of Bell's
palsy comparable to ENoG and H-B grade. OBJECTIVES: Several previous studies have
reported cases of Bell's palsy with vestibular function disorder. The basic
hypothesis behind this effect lies in the close proximity of the vestibular and
facial nerves in the internal auditory canal (IAC). Therefore, the aim of this
study was to investigate the correlation between Bell's palsy prognosis and
ocular vestibular evoked myogenic potentials (oVEMPs). METHODS: Total 104
consecutive patients who were diagnosed with Bell?s palsy from January 2012 to
December 2014 were enrolled. Patients were divided into complete recovery group
and incomplete recovery group. All of patients underwent oVEMP recordings within
1 week after disease onset. For the evaluation of correlation between H-B grades,
ENoG, oVEMP and Recovery of Bell?s palsy, logistic regression analysis was
performed. RESULTS: The mean value of ocular vemp asymmetry was significantly
higher in the incomplete recovery group than the complete recovery group (p <
0.05). No association was found between the ipsilesional PTA threshold, caloric
test, and rate of abnormal EMG and recovery state. However, the initial state of
ENoG, initial H-B grade, and oVEMP abnormal findings (Latency & Amplitude
symmetry ratio) were significantly correlated with the rate of recovery (p =
0.025, p = 0.013, and p < 0.005, respectively).
PMID- 27609664
TI - Effect of quercetin and resveratrol co-incorporated in liposomes against
inflammatory/oxidative response associated with skin cancer.
AB - The present investigation reports the development of liposomes for the co
delivery of naturally occurring polyphenols, namely quercetin and resveratrol.
Small, spherical, uni/bilamellar vesicles were produced, as demonstrated by light
scattering, cryo-TEM, SAXS. The incorporation of quercetin and resveratrol in
liposomes did not affect their intrinsic antioxidant activity, as DPPH radical
was almost completely inhibited. The cellular uptake of the polyphenols was
higher when they were formulated in liposomes, and especially when co-loaded
rather than as single agents, which resulted in a superior ability to scavenge
ROS in fibroblasts. The in vivo efficacy of the polyphenols in liposomes was
assessed in a mouse model of skin lesion. The topical administration of liposomes
led to a remarkable amelioration of the tissue damage, with a significant
reduction of oedema and leukocyte infiltration. Therefore, the proposed approach
based on polyphenol vesicular formulation may be of value in the treatment of
inflammation/oxidative stress associated with pre-cancerous/cancerous skin
lesions.
PMID- 27609666
TI - Design and Cellular Fate of Bioinspired Au-Ag Nanoshells@Hybrid Silica
Nanoparticles.
AB - Silica-coated gold-silver alloy nanoshells were obtained via a bioinspired
approach using gelatin and poly-l-lysine (PLL) as biotemplates for the
interfacial condensation of sodium silicate solutions. X-ray photoelectron
spectroscopy was used as an efficient tool for the in-depth and complete
characterization of the chemical features of nanoparticles during the whole
synthetic process. Cytotoxicity assays using HaCaT cells evidenced the
detrimental effect of the gelatin nanocoating and significant induction of late
apoptosis after silicification. In contrast, PLL-modified nanoparticles had less
biological impact that was further improved by the silica layer, and uptake rates
of up to 50% of those of the initial particles could be achieved. These results
are discussed considering the effect of nanosurface confinement of the
biopolymers on their chemical and biological reactivity.
PMID- 27609667
TI - Assessing women's satisfaction with family planning services in Mozambique.
AB - BACKGROUND: The contraceptive prevalence rate in Mozambique was estimated as
11.3% in the last Demographic and Health Survey. The impact of family planning
(FP) on women's health and on the reduction of maternal mortality is well known.
METHODS: Acknowledging the importance of user satisfaction in the utilisation of
health services, exit interviews were used to assess women's satisfaction with FP
services in Mozambique. The survey, conducted in 174 health facilities, was
representative at the national level, covered all provinces, and both urban and
rural areas. RESULTS: Overall, 86% of respondents were satisfied with FP
services, but issues such as insufficient supplies of oral contraceptives and the
low quality of healthcare provider/client interactions were given as reasons for
women's dissatisfaction. CONCLUSION: Defined actions at the level of health
service provision are needed to tackle the identified issues and ensure improved
satisfaction with, and better utilisation of, FP services in Mozambique.
PMID- 27609669
TI - Nucleus and nucleus-cytoskeleton connections in 3D cell migration.
AB - Cell migration plays an important role in many physiological and pathological
settings, ranging from embryonic development to cancer metastasis. Currently,
accumulating data suggest that cells migrating in three-dimensional (3D)
environments show well-defined differences compared to their well-established two
dimensional (2D) counterparts. During 3D migration, the cell body and nucleus
must deform to allow cellular passage through the available spaces, and the
deformability of the relatively rigid nucleus may constitute a limiting step.
Here, we highlight the key evidence regarding the role of the nuclear mechanics
in 3D migration, including the molecular components that govern the stiffness of
the nucleus and review how the nuclear dynamics are connected to and controlled
by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be
coordinated with the cytoskeletal dynamics at the leading and trailing edges,
which in turn impact the cytoplasmic dynamics that affect the migration
efficiency. Thus, we suggest that alterations in the nuclear structure may
facilitate cellular reorganizations that are necessary for efficient migration.
PMID- 27609668
TI - Computational imaging reveals mitochondrial morphology as a biomarker of cancer
phenotype and drug response.
AB - Mitochondria, which are essential organelles in resting and replicating cells,
can vary in number, mass and shape. Past research has primarily focused on short
term molecular mechanisms underlying fission/fusion. Less is known about longer
term mitochondrial behavior such as the overall makeup of cell populations'
morphological patterns and whether these patterns can be used as biomarkers of
drug response in human cells. We developed an image-based analytical technique to
phenotype mitochondrial morphology in different cancers, including cancer cell
lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of
different origins, including patient-derived xenografts, express highly diverse
mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell
population and fairly constant over time; (iii) mitochondrial patterns correlate
with cell metabolic measurements and (iv) therapeutic interventions can alter
mitochondrial phenotypes in drug-sensitive cancers as measured in pre- versus
post-treatment fine needle aspirates in mice. These observations shed light on
the role of mitochondrial dynamics in the biology and drug response of cancer
cells. On the basis of these findings, we propose that image-based mitochondrial
phenotyping can provide biomarkers for assessing cancer phenotype and drug
response.
PMID- 27609670
TI - Effects of Ilex paraguariensis (yerba mate) on the hypothalamic signalling of
insulin and leptin and liver dysfunction in adult rats overfed during lactation.
AB - Ilex paraguariensis (yerba mate) has a beneficial effect in the management of
obesity. Here, we studied the effects of yerba mate on hypothalamic changes in
leptin and insulin signalling, oxidative stress and liver morphology and
metabolism in postnatal early overfeeding (EO) Wistar rats. To induce EO, the
litter size was reduced to three pups per dam, and litters with 10 pups per dam
were used as a control (10 litters each). On postnatal day (PN) 150, EO offspring
were subdivided into EO and EO+mate groups (10 animals each), which were treated
with water or mate tea [1 g/kg body weight (BW)/day, by gavage], respectively,
for 30 days. The C offspring received water. On PN180, yerba mate treatment
prevented BW gain and reduced total body fat, visceral fat and food intake in
comparison with the EO group. Leptin and insulin signalling in the hypothalamus
measured by Western blotting was reduced only in the EO group. Yerba mate
treatment had a greater impact on insulin signalling normalization. In the liver,
yerba mate treatment normalized antioxidant enzyme activities and, consequently,
decreased lipid peroxidation, determined by malondialdehyde content. In addition,
the steatosis level and the liver triglyceride content were also restored. Thus,
for the first time, yerba mate was demonstrated to increase antioxidant defences
and improve liver metabolism in adult rats that were overfed during lactation,
possibly through improvements in the hypothalamic action of insulin. These
findings may be important for the treatment of obesity-related disorders.
PMID- 27609671
TI - Adaptability of expert visual anticipation in baseball batting.
AB - By manipulating stimulus variation in terms of opponent pitcher actions, this
study investigated the capability of expert (n = 30) and near-expert (n = 95)
professional baseball batters to adapt anticipation skill when using the video
simulation temporal occlusion paradigm. Participants watched in-game footage of
two pitchers, one after the other, that was temporally occluded at ball release
and various points during ball flight. They were required to make a written
prediction of pitch types and locations. Per cent accuracy was calculated for
pitch type, for pitch location, and for type and location combined. Results
indicated that experts and near-experts could adapt their anticipation to predict
above guessing level across both pitchers, but adaptation to the left-handed
pitcher was poorer than the right-handed pitcher. Small-to-moderate effect sizes
were found in terms of superior adaptation by experts over near-experts at the
ball release and early ball flight occlusion conditions. The findings of this
study extend theoretical and applied knowledge of expertise in striking sports.
Practical application of the instruments and findings are discussed in terms of
applied researchers, practitioners and high-performance staff in professional
sporting organisations.
PMID- 27609673
TI - Non-linear quantum-classical scheme to simulate non-equilibrium strongly
correlated fermionic many-body dynamics.
AB - We propose a non-linear, hybrid quantum-classical scheme for simulating non
equilibrium dynamics of strongly correlated fermions described by the Hubbard
model in a Bethe lattice in the thermodynamic limit. Our scheme implements non
equilibrium dynamical mean field theory (DMFT) and uses a digital quantum
simulator to solve a quantum impurity problem whose parameters are iterated to
self-consistency via a classically computed feedback loop where quantum gate
errors can be partly accounted for. We analyse the performance of the scheme in
an example case.
PMID- 27609672
TI - Acoustic diagnosis of pulmonary hypertension: automated speech- recognition
inspired classification algorithm outperforms physicians.
AB - We hypothesized that an automated speech- recognition-inspired classification
algorithm could differentiate between the heart sounds in subjects with and
without pulmonary hypertension (PH) and outperform physicians. Heart sounds,
electrocardiograms, and mean pulmonary artery pressures (mPAp) were recorded
simultaneously. Heart sound recordings were digitized to train and test speech
recognition-inspired classification algorithms. We used mel-frequency cepstral
coefficients to extract features from the heart sounds. Gaussian-mixture models
classified the features as PH (mPAp >= 25 mmHg) or normal (mPAp < 25 mmHg).
Physicians blinded to patient data listened to the same heart sound recordings
and attempted a diagnosis. We studied 164 subjects: 86 with mPAp >= 25 mmHg (mPAp
41 +/- 12 mmHg) and 78 with mPAp < 25 mmHg (mPAp 17 +/- 5 mmHg) (p < 0.005). The
correct diagnostic rate of the automated speech-recognition-inspired algorithm
was 74% compared to 56% by physicians (p = 0.005). The false positive rate for
the algorithm was 34% versus 50% (p = 0.04) for clinicians. The false negative
rate for the algorithm was 23% and 68% (p = 0.0002) for physicians. We developed
an automated speech-recognition-inspired classification algorithm for the
acoustic diagnosis of PH that outperforms physicians that could be used to screen
for PH and encourage earlier specialist referral.
PMID- 27609674
TI - Acute pancreatitis in ICU secondary to treatment with tigecycline.
AB - Tigecycline is a broad spectrum antimicrobial agent, structurally similar to
minocycline and that shares some tetracycline-related side effects. A case report
is presented on a 68-year-old female who received tigecycline for a sepsis of
unknown origin and who, in the following 5days, developed abdominal pain and
elevated pancreatic enzymes, which suggested acute pancreatitis. After ruling out
other origins, and according to the Naranjo adverse drug reaction probability
scale, tigecycline was the probable cause of the acute pancreatitis, a
complication that has been reported 5 times in the database of the Spanish
pharmacosurveillance system since 2009. Close monitoring of abdominal signs and
symptoms is recommended during treatment with tigecycline, since adverse effects
affecting the digestive system are the most prevalent ones when using this drug.
PMID- 27609675
TI - Nasogastric feeding tube located in the lung. SENSAR case of the trimester.
AB - A clinical case is presented that was communicated to Spanish Notification System
on Safety in Anaesthesia and Recovery (SENSAR). Using this communication and its
analysis, a strategy is obtained in order to reduce the risks associated with the
insertion of a nasogastric tube (NST) for enteral nutrition in adult patients in
the post-surgical recovery unit. A description of the incident is presented, an
analysis of its causes, and the measures that were introduced in order to avoid
similar incidents in the future, as well as to promote a safety culture in the
organisation. A description of associated incidents registered in SENSAR is also
given. The aim of this work is to describe, analyse and introduce safety measures
arising from incidents notified to SENSAR, associated with the insertion and
checking of the nutrition NST in adult patients in the post-surgical recovery
unit.
PMID- 27609676
TI - Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study.
AB - BACKGROUND: Patients with long duration of atrial fibrillation (AF), enlarged
atria, or failed catheter ablation have advanced AF and may require more
extensive treatment than pulmonary vein isolation. OBJECTIVES: The aim of this
study was to investigate the efficacy and safety of additional ganglion plexus
(GP) ablation in patients undergoing thoracoscopic AF surgery. METHODS: Patients
with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent
AF also received additional lines (Dallas lesion set). Patients were randomized
1:1 to additional epicardial ablation of the 4 major GPs and Marshall's ligament
(GP group) or no extra ablation (control) and followed every 3 months for 1 year.
After a 3-month blanking period, all antiarrhythmic drugs were discontinued.
RESULTS: Two hundred forty patients with a mean AF duration of 5.7 +/- 5.1 years
(59% persistent) were included. Mean procedure times were 185 +/- 54 min and 168
+/- 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123),
respectively. GP ablation abated 100% of evoked vagal responses; these responses
remained in 87% of control subjects. Major bleeding occurred in 9 patients (all
in the GP group; p < 0.001); 8 patients were managed thoracoscopically, and 1
underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP
group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in
the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group,
not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF
recurrence in the GP and control groups was not statistically different whether
patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not
taking antiarrhythmic drugs. CONCLUSIONS: GP ablation during thoracoscopic
surgery for advanced AF has no detectable effect on AF recurrence but causes more
major adverse events, major bleeding, sinus node dysfunction, and pacemaker
implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via
Thoracoscopic Surgery [AFACT]; NCT01091389).
PMID- 27609677
TI - Surgical Ganglionic Plexus Ablation in Atrial Fibrillation: Is All Hope Lost for
the Plexus?
PMID- 27609678
TI - Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling:
ENGAGE AF-TIMI 48 Analysis.
AB - BACKGROUND: Anticoagulation is often avoided in patients with atrial fibrillation
who are at an increased risk of falling. OBJECTIVES: This study assessed the
relative efficacy and safety of edoxaban versus warfarin in the ENGAGE AF-TIMI 48
(Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation
Thrombolysis In Myocardial Infarction 48) trial in patients with atrial
fibrillation judged to be at increased risk of falling. METHODS: We performed a
pre-specified analysis of the ENGAGE AF-TIMI 48, comparing patients with versus
without increased risk of falling. RESULTS: Nine hundred patients (4.3%) were
judged to be at increased risk of falling. These patients were older (median, 77
vs. 72 years; p < 0.001), and had a higher prevalence of comorbidities including
prior stroke/transient ischemic attack, diabetes, and coronary artery disease.
After multivariable adjustment, patients at increased risk of falling experienced
more bone fractures caused by falling (adjusted hazard ratio [HRadj]: 1.88; 95%
confidence interval [CI]: 1.49 to 2.38; p < 0.001), major bleeding (HRadj: 1.30;
95% CI: 1.04 to 1.64; p = 0.023), life-threatening bleeding (HRadj: 1.67; 95% CI:
1.11 to 2.50; p = 0.013), and all-cause death (HRadj: 1.45; 95% CI: 1.23 to 1.70;
p < 0.001), but not ischemic events including stroke/systemic embolic event
(HRadj: 1.16; 95% CI: 0.89 to 1.51; p = 0.27). No treatment interaction was
observed between either dosing regimens of edoxaban and warfarin for the efficacy
and safety outcomes. Treatment with edoxaban resulted in a greater absolute risk
reduction in severe bleeding events and all-cause mortality compared with
warfarin. CONCLUSIONS: Edoxaban is an attractive alternative to warfarin in
patients at increased risk of falling, because it is associated with an even
greater absolute reduction in severe bleeding events and mortality. (Effective
aNticaoGulation with factor xA next Generation in Atrial Fibrillation [ENGAGE AF
TIMI 48]; NCT00781391).
PMID- 27609679
TI - Atrial Fibrillation and Fall Risk: What Are the Treatment Implications?
PMID- 27609680
TI - Long-Term Prognosis of Deferred Acute Coronary Syndrome Lesions Based on
Nonischemic Fractional Flow Reserve.
AB - BACKGROUND: Deferring percutaneous coronary intervention in nonischemic lesions
by fractional flow reserve (FFR) is associated with excellent long-term prognosis
in patients with stable ischemic heart disease (SIHD). Although FFR is
increasingly used for clinical decision making in acute coronary syndrome (ACS)
patients with intermediate lesions, its effect on long-term prognosis has not
been well established. OBJECTIVES: This study investigated the clinical and
prognostic utility of FFR in ACS patients with percutaneous coronary intervention
deferred on the basis of nonischemic FFR. METHODS: We studied 206 consecutive ACS
patients with 262 intermediate lesions and 370 patients with SIHD (528 lesions)
in whom revascularization was deferred on the basis of a nonischemic FFR (>0.75).
The primary outcome measure was a composite of myocardial infarction and target
vessel failure (major adverse cardiovascular events [MACE]). RESULTS: In the
entire cohort, the long-term (3.4 +/- 1.6 years) MACE rate was higher in the ACS
group than in the SIHD group (23% vs. 11%, p < 0.0001). After propensity score
matching (200 patients/group), MACE remained significantly higher (ACS 25% vs.
SIHD 12%; p < 0.0001). On Cox proportional hazards analysis for MACE, ACS had a
hazard ratio of 2.8 (95% confidence interval: 1.9 to 4.0; p < 0.0001). In both
the matched and unmatched cohorts, across all FFR categories, ACS patients had a
significantly higher annualized myocardial infarction/target vessel
revascularization rate compared with SIHD (p < 0.05). Receiver-operating
characteristic analysis identified FFR cutoffs (best predictive accuracy for
MACE) of <0.84 for ACS (MACE 21% vs. 36%; p = 0.007) and <0.81 for SIHD (MACE 17%
vs. 9%; p = 0.01). CONCLUSIONS: Deferring percutaneous coronary intervention on
the basis of nonischemic FFR in patients with an initial presentation of ACS is
associated with significantly worse outcomes than SIHD. Caution is warranted in
using FFR values derived from patients with SIHD for clinical decision making in
ACS patients.
PMID- 27609681
TI - Fractional Flow Reserve in Acute Coronary Syndromes.
PMID- 27609683
TI - Transcatheter Aortic Valve Replacement for Bicuspid Aortic Stenosis: Are We Ready
for the Challenge?
PMID- 27609682
TI - Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in
Bicuspid Aortic Valve Stenosis.
AB - BACKGROUND: Few studies have evaluated the clinical outcomes of transcatheter
aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis
(AS). Particularly, limited data exist comparing the results of TAVR with new
generation devices versus early-generation devices. OBJECTIVES: This study sought
to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new
generation devices. METHODS: The Bicuspid TAVR Registry is an international
multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR
between April 2005 and May 2015. RESULTS: Of 301 patients, 199 patients (71.1%)
were treated with early-generation devices (Sapien XT [Edwards Lifesciences
Corporation, Irvine, California]: n = 87; CoreValve [Medtronic, Minneapolis,
Minnesota]: n = 112) and 102 with new-generation devices (Sapien 3 [Edwards
Lifesciences Corporation]: n = 91; Lotus [Boston Scientific Corporation,
Marlborough, Massachusetts]: n = 11). The mean Society of Thoracic Surgeons score
was 4.7 +/- 5.2 without significant differences between groups (4.6 +/- 5.1 vs.
4.9 +/- 5.4; p = 0.57). Overall, all-cause mortality rates were 4.3% at 30 days
and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and
significantly less frequent with new-generation compared to early-generation
devices (0.0% vs. 8.5%; p = 0.002), which resulted in a higher device success
rate (92.2% vs. 80.9%; p = 0.01). There were no differences between early- and
new-generation devices in stroke (2.5% vs. 2.0%; p > 0.99), life-threatening
bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; p
= 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety
endpoints (15.1% vs. 10.8%; p = 0.30), and 30-day all-cause mortality (4.5% vs.
3.9%; p > 0.99). CONCLUSIONS: The clinical outcomes of TAVR in patients with
bicuspid AS were favorable. New-generation devices were associated with less
paravalvular leak and, hence, a higher device success rate than early-generation
devices. (The Bicuspid Aortic Stenosis Following Transcatheter Aortic Valve
Replacement Registry [Bicuspid TAVR]; NCT02394184).
PMID- 27609684
TI - Risk of Aortic Dissection in the Moderately Dilated Ascending Aorta.
AB - BACKGROUND: Recent studies have demonstrated that many patients with acute type A
aortic dissection (AD) have aortic diameters of <55 mm at presentation, prompting
discussion of lowering the prophylactic surgical guidelines. However, risk of
dissection at these smaller diameters is poorly defined. OBJECTIVES: The purpose
of this study is to understand the risk of AD in moderately dilated ascending
aortas using a large echocardiographic data set. METHODS: Using an institutional
echocardiography database, we identified 4,654 nonsyndromic adults (age: 68.6 +/-
13.1 years; 1,003 women) with maximal ascending aortic diameters of 40 to 55 mm.
We performed competing risk analysis to determine the independent risk factors of
AD or aortic rupture. RESULTS: Five hundred eighty-six individuals (12.6%) had
bicuspid aortic valves (BAVs). During follow-up (14,431.5 patient-years), AD and
rupture occurred in 13 and 1 patients, respectively, which demonstrated a
linearized incidence of AD and/or rupture of 0.1% per patient-year. Elective
ascending aortic repair was performed in 176 individuals. On multivariable
analyses, independent predictors of AD and/or rupture were age (hazard ratio
[HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p= 0.024) and baseline
aortic diameters (HR: 1.20; 95% CI: 1.05 to 1.36; p = 0.006). The presence of a
BAV was not a significant factor (HR: 0.94; 95% CI: 0.10 to 8.40; p = 0.95).
Estimated risks of AD and/or rupture within 5 years were 0.4%, 1.1%, and 2.9% at
baseline aortic diameters of 45, 50, and 55 mm, respectively. CONCLUSIONS: Risks
of AD and/or rupture were significantly correlated with the aortic diameter and
age in patients with moderately dilated ascending aortas. However, the risks were
low for diameters <5.0 cm when timely elective aortic repair was performed,
regardless of the morphology of the aortic valve.
PMID- 27609685
TI - Aortic Risk Redux.
PMID- 27609686
TI - Long-Term P2Y12-Receptor Antagonists in Post-Myocardial Infarction Patients:
Facing a New Trilemma?
AB - Physicians considering prescription of P2Y12-receptor antagonist for long-term
(>1 year) protection of patients post-myocardial infarction face the trilemma of
selecting between clopidogrel, prasugrel, or ticagrelor. Differential ischemic
benefits derived from relevant trials may assist in tailoring treatment, although
the different bleeding definitions applied make any meaningful comparison of each
agent's bleeding potential very difficult. Considering the available data and
recognizing the significant limitation of observations obtained thus far from
subgroup analyses, prasugrel appears to provide higher anti-ischemic protection
than clopidogrel. Ticagrelor seems to be an attractive option for patients with
renal dysfunction, peripheral arterial disease, or following a brief P2Y12
receptor antagonist interruption, whereas clopidogrel may be advised in the
presence of cost and availability issues. As head-to-head comparative trials
between P2Y12-receptor antagonists are lacking, selection of a specific agent by
the clinician should be made on the basis of critical appraisal of available
large clinical datasets.
PMID- 27609688
TI - Myocardial Infarction-Associated Circular RNA Predicting Left Ventricular
Dysfunction.
PMID- 27609687
TI - Left Main Coronary Artery Disease: Secular Trends in Patient Characteristics,
Treatments, and Outcomes.
AB - Left main coronary artery (LMCA) disease is the highest-risk lesion subset of
ischemic heart disease, and has traditionally been an indication for coronary
artery bypass grafting (CABG). Recent evidence suggests comparable clinical
outcomes between percutaneous coronary intervention (PCI) and CABG for LMCA
disease, with similar rates of mortality and serious composite outcomes, a higher
rate of stroke with CABG, and a higher rate of repeat revascularization with PCI.
These results have been translated to the current guideline recommendation that
PCI is a reasonable alternative to CABG in patients with low to intermediate
anatomic complexity. However, how the characteristics, treatment, and clinical
outcomes of patients with unprotected LMCA disease have evolved over time has not
yet been fully evaluated. We therefore described secular trends in the
characteristics and long-term outcomes of unprotected LMCA disease using "real
world" clinical experience from the IRIS-MAIN (Interventional Research
Incorporation Society-Left MAIN Revascularization) registry together with a broad
review of this topic.
PMID- 27609689
TI - Electrical Storms in Patients With Implantable Cardioverter-Defibrillators for
Primary Prevention.
PMID- 27609690
TI - Changes in Plaque Composition and the Pleiotropic Effects of Statins.
PMID- 27609691
TI - STABLE Versus Non-STABLE Studies: Effects of Rosuvastatin on Modifying Coronary
Plaques.
PMID- 27609692
TI - The Paradox of Heart Failure and Atrial Fibrillation.
PMID- 27609693
TI - Reply: The Paradox of Heart Failure and Atrial Fibrillation.
PMID- 27609694
TI - Correction.
PMID- 27609695
TI - Levels of depression and satisfaction with life as indicators of health services
consumption.
AB - OBJECTIVE: To evaluate the correlation between depression, satisfaction with
life, and primary healthcare services consumption. METHODS: A random sample of
primary healthcare clinic patients agreed to complete self-report questionnaires
on demographics and physical activity, the Geriatric Depression Scale (GDS),
Satisfaction with Life Scale and the Visual Analog Scale for Happiness. Treating
physicians completed the Cumulative Illness Rating Scale (CIRS) for each patient.
The relationships among psychometric, medical, the number of visits to health
maintenance organization (HMO)-physicians during the previous year was assessed.
RESULTS: Positive correlation was found between visits to HMO-physicians and
depression severity, as assessed by GDS (p = .049), and between visits/year and
illness severity, as measured by CIRS (p < .001). Correlation was also found
between depression and number of chronic medications used (p = .005). Physical
activity correlated inversely with depression severity (p = .014). Gender and
income had no impact on frequency of visits to HMO-physicians, depression, or
satisfaction with life. CONCLUSIONS: The results indicate that there is a
correlation between depression and healthcare service consumption, as represented
by number of HMO-physician visits and medication use. Thus, early detection of
depression, using tools such as GDS, and early initiation of antidepressive
treatment may help to lower the burden on the health system.
PMID- 27609696
TI - Costing 'healthy' food baskets in Australia - a systematic review of food price
and affordability monitoring tools, protocols and methods.
AB - OBJECTIVE: To undertake a systematic review to determine similarities and
differences in metrics and results between recently and/or currently used tools,
protocols and methods for monitoring Australian healthy food prices and
affordability. DESIGN: Electronic databases of peer-reviewed literature and
online grey literature were systematically searched using the PRISMA approach for
articles and reports relating to healthy food and diet price assessment tools,
protocols, methods and results that utilised retail pricing. SETTING: National,
state, regional and local areas of Australia from 1995 to 2015. SUBJECTS:
Assessment tools, protocols and methods to measure the price of 'healthy' foods
and diets. RESULTS: The search identified fifty-nine discrete surveys of
'healthy' food pricing incorporating six major food pricing tools (those used in
multiple areas and time periods) and five minor food pricing tools (those used in
a single survey area or time period). Analysis demonstrated methodological
differences regarding: included foods; reference households; use of availability
and/or quality measures; household income sources; store sampling methods; data
collection protocols; analysis methods; and results. CONCLUSIONS: 'Healthy' food
price assessment methods used in Australia lack comparability across all metrics
and most do not fully align with a 'healthy' diet as recommended by the current
Australian Dietary Guidelines. None have been applied nationally. Assessment of
the price, price differential and affordability of healthy (recommended) and
current (unhealthy) diets would provide more robust and meaningful data to inform
health and fiscal policy in Australia. The INFORMAS 'optimal' approach provides a
potential framework for development of these methods.
PMID- 27609697
TI - Feasibility testing of smart tablet questionnaires compared to paper
questionnaires in an amputee rehabilitation clinic.
AB - BACKGROUND: Capturing the variability that exists among patients attending an
amputee clinic using standardized paper-based questionnaires is time-consuming
and may not be practical for routine clinical use. Electronic questionnaires are
a potential solution; however, the benefits are dependent on the feasibility and
acceptance of this mode of data collection among patients. OBJECTIVE: To
determine the feasibility and patient preference/comfort in using a tablet-based
questionnaire for data collection in an outpatient amputee rehabilitation clinic
compared to a traditional paper-based questionnaire. STUDY DESIGN: Observational
study. METHODS: In all, 48 patients with major extremity amputations completed
both tablet and paper questionnaires related to their amputation and prosthetic
use. Both trials were timed; patients then completed a semi-structured
questionnaire about their experience. RESULTS: In all, 20.5% of patients needed
hands-on assistance completing the paper questionnaire compared to 20.8% for the
tablet. The majority of participants (52.1%) indicated a preference for the
tablet questionnaire; 64.6% of patients felt the tablet collected a more complete
and accurate representation of their status and needs. In all, 70.8% of
participants described themselves as comfortable using the tablet. CONCLUSION:
Despite comorbidities, patients with amputations demonstrated excellent
acceptance of the electronic tablet-based questionnaire. Tablet questionnaires
have significant potential advantages over paper questionnaires and should be
further explored. Clinical relevance A custom electronic questionnaire was found
to be beneficial for routine clinic use and was well received by patients in an
amputee rehabilitation clinic. Development of such questionnaires can provide an
efficient mechanism to collect meaningful data that can be used for individual
patient care and program quality improvement initiatives.
PMID- 27609698
TI - Estimation of true height: a study in population-specific methods among young
South African adults.
AB - OBJECTIVE: To investigate the accuracy of arm-associated height estimation
methods in the calculation of true height compared with stretch stature in a
sample of young South African adults. DESIGN: A cross-sectional descriptive
design was employed. SETTING: Pietermaritzburg, Westville and Durban, KwaZulu
Natal, South Africa, 2015. SUBJECTS: Convenience sample (N 900) aged 18-24 years,
which included an equal number of participants from both genders (150 per gender)
stratified across race (Caucasian, Black African and Indian). RESULTS: Continuous
variables that were investigated included: (i) stretch stature; (ii) total
armspan; (iii) half-armspan; (iv) half-armspan *2; (v) demi-span; (vi) demi-span
gender-specific equation; (vii) WHO equation; and (viii) WHO-adjusted equations;
as well as categorization according to gender and race. Statistical analysis was
conducted using IBM SPSS Statistics Version 21.0. Significant correlations were
identified between gender and height estimation measurements, with males being
anatomically larger than females (P<0.001). Significant differences were
documented when study participants were stratified according to race and gender
(P<0.001). Anatomical similarities were noted between Indians and Black Africans,
whereas Caucasians were anatomically different from the other race groups. Arm
associated height estimation methods were able to estimate true height; however,
each method was specific to each gender and race group. CONCLUSIONS: Height can
be calculated by using arm-associated measurements. Although universal equations
for estimating true height exist, for the enhancement of accuracy, the use of
equations that are race-, gender- and population-specific should be considered.
PMID- 27609700
TI - A starfish robot based on soft and smart modular structure (SMS) actuated by SMA
wires.
AB - This paper describes the design, fabrication and locomotion of a starfish robot
whose locomotion principle is derived from a starfish. The starfish robot has a
number of tentacles or arms extending from its central body in the form of a
disk, like the topology of a real starfish. The arm, which is a soft and
composite structure (which we call the smart modular structure (SMS)) generating
a planar reciprocal motion with a high speed of response upon the actuation
provided by the shape memory alloy (SMA) wires, is fabricated from soft and smart
materials. Based on the variation in the resistance of the SMA wires during their
heating, an adaptive regulation (AR) heating strategy is proposed to (i) avoid
overheating of the SMA wires, (ii) provide bending range control and (iii)
achieve a high speed of response favorable to successfully propelling the
starfish robot. Using a finite-segment method, a thermal dynamic model of the SMS
is established to describe its thermal behavior under the AR and a constant
heating strategy. A starfish robot with five SMS tentacles was tested with
different control parameters to optimize its locomotion speed. As demonstrated in
the accompanying video file, the robot successfully propelled in semi-submerged
and underwater environments show its locomotion ability in the multi-media, like
a real starfish. The propulsion speed of the starfish robot is at least an order
of magnitude higher than that of those reported in the literature-thanks to the
SMS controlled with the AR strategy.
PMID- 27609699
TI - Effect of wheat hay particle size and replacement of wheat hay with wheat silage
on rumen pH, rumination and digestibility in ruminally cannulated non-lactating
cows.
AB - This study examined the effects on intake, diurnal rumen pH changes, rumination
and digestibility of feeding ruminally cannulated non-lactating cows in a Latin
square design (four cows*four periods) with four total mixed rations (TMRs)
typical for lactating cows. TMRs were based on: long wheat hay or short wheat
hay, wheat silage or wheat silage+1.5% NaHCO3 buffer, as the sole roughage source
(30% of TMR dry matter (DM)). The level of physically effective NDF remaining
above the 8 mm screen (peNDF) was similar in the long hay and silage-based TMRs
(9.45% to 9.64% of DM) and lower in the short hay TMR (7.47% of DM). The four
TMRs were offered individually at 95% of ad libitum intake to avoid orts within
24 h. Cows fed long hay consumed less DM than the short hay and silage groups
(9.6 v. 10.5 and 10.8 kg/day, respectively) and sorted against large hay
particles at 12 h post-feeding. Under the limitations of this study (non
lactating cows fed at restricted intake) short hay TMR prevented sorting within
12 h post-feeding, encouraged rumination per kg peNDF ingested, and had higher
average rumen pH (6.24), whereas preventing sub acute ruminal acidosis (SARA,
defined as pH<5.8 for at least 5 h/day). In contrast, the long hay and silage
based groups were under SARA. In vitro methane production of rumen fluid was
higher in the hay-fed cows than in their silage-fed counterparts, and in all
treatments lower at 1 h pre-feeding than at 6 h post-feeding. In vivo DM and NDF
digestibility were similar for the short hay and silage TMRs, and higher than
those of the long hay TMR. Under the conditions of this study, addition of 1.5%
buffer to the wheat silage TMR had no effect on intake, rumen pH, creation of
SARA and digestibility.
PMID- 27609701
TI - Mechanotransduction-Induced Lipid Production System with High Robustness and
Controllability for Microalgae.
AB - Microalgae lipids are a promising energy source, but current biochemical methods
of lipid-inductions such as nitrogen deprivation have low process robustness and
controllability. Recently, use of mechanotransduction based membrane distortion
by applying compression stress in a 2D-microsystem was suggested as a way to
overcome these limitations of biochemical induction. However, reproduction in
large numbers of cells without cell death has been difficult to overcome because
compression for direct membrane distortion reduces culture volume and leads to
cell death due to nutrient deprivation. In this study, a mechanotransduction
induced lipid production (MDLP) system that redirects elastic microbeads to
induce membrane distortion of microalgae with alleviating cell death was
developed. This system resulted in accumulation of lipid in as little as 4 hr.
Once compressed, porous microbeads absorb media and swell simultaneously while
homogeneously inducing compression stress of microalgae. The absorbed media
within beads could be supplied to adjacent cells and could minimize cell death
from nutrient deficiency. All mechanotransduction was confirmed by measuring
upregulation of calcium influx and Mat3 genes. The microbeads ensured robustness
and controllability in repeated compression/de-compression processes. Overall,
the MDLP system has potential for use as a fundamental biodiesel process that
requires robustness and controllability.
PMID- 27609702
TI - Illness absenteeism rates in primary and secondary schools in 2013-2014 in
England: was there any impact of vaccinating children of primary-school age
against influenza?
AB - A phased introduction of routine influenza vaccination of healthy children was
recommended in the UK in 2012, with the aim of protecting both vaccinated
children and the wider population through reducing transmission. In the first
year of the programme in 2013-2014, 4- to 11-year-olds were targeted in pilot
areas across England. This study assesses if this was associated with school
absenteeism, an important societal burden of influenza. During the spring 2014
term when influenza predominantly circulated, the proportion of absence sessions
due to illness was compared between vaccination pilot and non-pilot areas for
primary schools (to measure overall impact) and secondary schools (to measure
indirect impact). A linear multilevel regression model was applied, adjusting for
clustering within schools and potential school-level confounders, including
deprivation, past absenteeism, and ethnicity. Low levels of influenza activity
were reported in the community in 2013-2014. Primary schools in pilot areas had a
significantly adjusted decrease in illness absenteeism of 0.05% relative to non
pilot schools; equivalent to an average of 4 days per school. In secondary
schools, there was no significant indirect impact of being located in a pilot
area on illness absenteeism. These insights can be used in conjunction with
routine healthcare surveillance data to evaluate the full benefits of such a
programme.
PMID- 27609704
TI - Rosai-Dorfman Disease Masquerading as Cholangiocarcinoma.
PMID- 27609703
TI - Long-term Recurrence-free Survival After Standard Endoscopic Resection Versus
Surgical Resection of Submucosal Invasive Colorectal Cancer: A Population-based
Study.
AB - BACKGROUND & AIMS: There is controversy over the optimal management for T1
colorectal cancer (T1 CRC). This study compared initial endoscopic resection with
or without additional surgery, or initial surgery for T1 CRC, and assessed risk
factors for lymph node metastases (LNMs) and long-term recurrence. METHODS: We
performed a registration study that included all patients diagnosed with T1 CRC
from 1995 through 2011 in the southeast area of The Netherlands (n = 1315). High
risk histology (with regard to LNM) was defined as the presence of poor
differentiation, lymphangio-invasion, and/or deep submucosal invasion. The
primary outcome measure was the combined rate of local and distant CRC recurrence
during a mean follow-up period of 6.6 years. Logistic regression and Cox
proportional hazards regression analyses were performed to evaluate independent
risk factors for LNM and CRC recurrence, respectively. RESULTS: Endoscopic
resection was performed in 590 patients (44.9%); of these, 220 (16.7%) underwent
additional surgery. Initial surgery was performed in 725 patients (55.1%). The
risk of LNM was higher in T1 CRC with histologic risk factors (15.5% vs 7.1%
without histologic risk factors; odds ratio, 2.21; 95% confidence interval, 1.33
3.70). Thirty-day mortality did not differ between patients who received
additional surgery (0.9%) and those who underwent only endoscopic resection
(1.4%; P = .631). Rates of CRC recurrence were 6.2% (9.8/1000 patient-years)
after only endoscopic resection vs 6.4% (9.4/1000 patient-years) after additional
surgery (P = .912), and 3.4% (5.2/1000 patient-years) after initial surgery (P =
.031). In multivariate analysis, this difference was not significant. The only
independent risk factor for long-term recurrence was a positive resection margin
(hazard ratio, 6.88; 95% confidence interval, 2.27-20.87). CONCLUSIONS: Based on
a population analysis of patients diagnosed with T1 CRC, additional surgery after
endoscopic resection should be considered only for patients with high-risk
histology or a positive resection margin.
PMID- 27609705
TI - Disparities in Liver Transplantation Resulting From Variations in Regional Donor
Supply and Multiple Listing Practices.
PMID- 27609706
TI - Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort.
AB - BACKGROUND & AIMS: Pancreatitis is a source of substantial morbidity and health
cost in the United States. Little is known about how diet might contribute to its
pathogenesis. To characterize dietary factors that are associated with risk of
pancreatitis by disease subtype, we conducted a prospective analysis of 145,886
African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in
the Multiethnic Cohort. METHODS: In the Multiethnic Cohort (age at baseline, 45
75 y), we identified cases of pancreatitis using hospitalization claim files from
1993 through 2012. Patients were categorized as having gallstone-related acute
pancreatitis (AP) (n = 1210), AP not related to gallstones (n = 1222), or
recurrent AP or suspected chronic pancreatitis (n = 378). Diet information was
obtained from a questionnaire administered when the study began. Associations
were estimated by hazard ratios and 95% confidence intervals using Cox
proportional hazard models adjusted for confounders. RESULTS: Dietary intakes of
saturated fat (P trend = .0011) and cholesterol (P trend = .0008) and their food
sources, including red meat (P trend < .0001) and eggs (P trend = .0052), were
associated positively with gallstone-related AP. Fiber intake, however, was
associated inversely with gallstone-related AP (P trend = .0005) and AP not
related to gallstones (P trend = .0035). Vitamin D, mainly from milk, was
associated inversely with gallstone-related AP (P trend = .0015), whereas coffee
consumption protected against AP not related to gallstones (P trend < .0001).
With the exception of red meat, no other dietary factors were associated with
recurrent acute or suspected chronic pancreatitis. CONCLUSIONS: Associations
between dietary factors and pancreatitis were observed mainly for gallstone
related AP. Interestingly, dietary fiber protected against AP related and
unrelated to gallstones. Coffee drinking protected against AP not associated with
gallstones. Further studies are warranted to confirm our findings.
PMID- 27609707
TI - Decrease in Incidence of Colorectal Cancer Among Individuals 50 Years or Older
After Recommendations for Population-based Screening.
AB - BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) in the United States
is increasing among adults younger than 50 years, but incidence has decreased
among older populations after population-based screening was recommended in the
late 1980s. Blacks have higher incidence than whites. These patterns have
prompted suggestions to lower the screening age for average-risk populations or
in blacks. At the same time, there has been controversy over whether reductions
in CRC incidence can be attributed to screening. We examined age-related and race
related differences in CRC incidence during a 40-year time period. METHODS: We
determined the age-standardized incidence of CRC from 1975 through 2013 by using
the population-based Surveillance, Epidemiology, and End Results (SEER) program
of cancer registries. We calculated incidence for 5-year age categories (20-24
years through 80-84 years and 85 years or older) for different time periods (1975
1979, 1980-1984, 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010
2013), tumor subsite (proximal colon, descending colon, and rectum), and stages
at diagnosis (localized, regional, and distant). Analyses were stratified by race
(white vs black). RESULTS: There were 450,682 incident cases of CRC reported to
the SEER registries during the entire period (1975-2013). Overall incidence was
75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked
during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the
decreases in incidence between the time periods of 1980-1984 and 2010-2013 were
limited to the screening-age population (ages 50 years or older). Between these
time periods, there was 40% decrease in incidence among whites compared with 26%
decrease in incidence among blacks. Decreases in incidence were greater for
cancers of the distal colon and rectum, and reductions in these cancers were
greater among whites than blacks. CRC incidence among persons younger than 50
years decreased slightly between 1975-1979 and 1990. However, among persons 20-49
years old, CRC incidence increased from 8.3/100,000 persons in 1990-1994 to
11.4/100,000 persons in 2010-2013; incidence rates in younger adults were similar
for whites and blacks. CONCLUSIONS: On the basis of an analysis of the SEER
cancer registries from 1975 through 2013, CRC incidence decreased only among
individuals 50 years or older between the time periods of 1980-1984 and 2010
2013. Incidence increased modestly among individuals 20-49 years old between the
time periods of 1990-1994 and 2010-2013. The decision of whether to recommend
screening for younger populations requires a formal analysis of risks and
benefits. Our observed trends provide compelling evidence that screening has had
an important role in reducing CRC incidence.
PMID- 27609708
TI - [Fibrates therapy: Rational use fenofibrate 2016. Executive summary].
AB - To control lipid factors risk, beyond proper management of LDL cholesterol
according to individual risk, detection and treatment of atherogenic dyslipidemia
and abnormal levels of triglycerides or HDL cholesterol it should be considered
for address a global cardiovascular protection, both in primary and secondary
prevention. In this sense, these recommendations collect data on efficacy and
safety about the combination statin with fibrates, often necessary for total
control of dyslipidemia, particularly in patients with metabolic disorders such
as diabetes mellitus, metabolic syndrome or visceral obesity. Reference to
control and monitoring of treatment is also done, as well as benefits of
fenofibrate not linked directly to their lipid-lowering effect.
PMID- 27609709
TI - Interventions for enhancing return to work in individuals with a common mental
illness: systematic review and meta-analysis of randomized controlled trials.
AB - Common mental disorders (CMDs) are highly prevalent in the working population,
and are associated with long-term sickness absence and disability. Workers on
sick leave with CMDs would benefit from interventions that enable them to
successfully return to work (RTW). However, the effectiveness of RTW
interventions for workers with a CMD is not well studied. The objective of this
review is to assess the effectiveness of existing workplace and clinical
interventions that were aimed at enhancing RTW. A systematic review of studies of
interventions for improving RTW in workers with a CMD was conducted. The main
outcomes were proportion of RTW and sick-leave duration until RTW. Randomized
controlled trials (RCTs) were identified from Medline/PubMed, PsycINFO, EMBASE,
SocINDEX, and Human resource and management databases from January 1995 to 2016.
Two authors independently selected studies, assessed risk of bias and extracted
data. We pooled studies that we deemed sufficiently homogeneous in different
comparison groups and assessed the overall quality of the evidence. We reviewed
2347 abstracts from which 136 full-text articles were reviewed and 16 RCTs were
included in the analysis. Combined results from these studies suggested that the
available interventions did not lead to improved RTW rates over the control group
[pooled risk ratio 1.05, 95% confidence interval (CI) 0.97-1.12], but reduced the
number of sick-leave days in the intervention group compared to the control
group, with a mean difference of -13.38 days (95% CI -24.07 to -2.69).
PMID- 27609710
TI - Mandibular distraction osteogenesis: a systematic review of stability and the
effects on hard and soft tissues.
AB - Mandibular distraction osteogenesis (MDO) has been widely adopted in modern
maxillofacial surgery due to its less invasive approach and the consistent
aesthetic and functional improvements obtained. The aim of the present systematic
review was to analyze the available evidence on the skeletal and soft tissue
effects of MDO. The medical literature was searched to identify all peer-reviewed
papers meeting the selection criteria for the final review process. A three-point
grading system was used to rate the methodological quality of the selected
papers. The PICO approach was used to extract data from the selected papers. The
search strategy yielded eight relevant publications. The quality of the collected
evidence was low to moderate. Vertical and sagittal skeletal dimensions increased
significantly, by a mean of 5-10mm (P<0.05). Regarding the sagittal positioning
of the lips and surrounding structures, a 90% correspondence between skeletal and
soft tissue cephalometric points was observed. Significant skeletal relapse was
reported, however it did not worsen the results of treatment significantly.
PMID- 27609712
TI - Midterm Results of Descemet Membrane Endothelial Keratoplasty: 4 to 7 Years
Clinical Outcome.
AB - PURPOSE: To evaluate the midterm outcomes of Descemet membrane endothelial
keratoplasty (DMEK) up to 4-7 years postoperatively. DESIGN: Retrospective,
consecutive interventional case series. METHODS: A total of 250 consecutive eyes
of 209 patients who underwent DMEK at our institute and had potentially at least
4 years of follow-up. Main outcome measures were best-corrected visual acuity
(BCVA), endothelial cell density (ECD), central corneal thickness (CCT), graft
survival rate, and postoperative complications. RESULTS: At 6 months
postoperatively, 73% of the eyes reached a BCVA of >=20/25 (0.8) and 44% >=20/20
(1.0), and remained stable up to 7 years (P = .7114). ECD dropped by 33.9% in the
first 6 months, and then declined by a yearly rate of 9.0%. CCT did not show a
significant change after 6 months up to 7 years (P = .8447). The cumulative graft
survival rate at 4 and 7 years was 0.96 (95% confidence interval [0.93, 0.99]).
Rebubbling procedures were performed in 4.4% of eyes, all within the first 6
postoperative months. Repeat transplantations were performed in 15.2% of cases to
manage greater than one third graft detachment (11.6%), primary graft failure
(1.6%), or secondary graft failure (2.0%), with the majority (79%) of repeat
transplantations performed within the first year. After 6 months, the main
complications were allograft rejection (2.4%) and secondary graft failure (2.0%).
CONCLUSIONS: The visual acuity level achieved at 6 months after DMEK may remain
stable up to at least 4-7 years; ECD shows a constant, slow decrease; and
complications after the first 6 months occur in <5% of cases.
PMID- 27609713
TI - Splitting of the Recipient's Descemet Membrane in Descemet Membrane Endothelial
Keratoplasty-Ultrastructure and Clinical Relevance.
AB - PURPOSE: In Descemet membrane endothelial keratoplasty (DMEK), lamellar splitting
of the Descemet membrane (DM) may occur during stripping of host DM, leaving
residual DM on the recipient's DMEK interface. The purpose of this study was to
determine the incidence rate of lamellar splitting of DM during DMEK and to
describe the ultrastructure of DM in these eyes. DESIGN: Retrospective
consecutive case series. METHODS: setting: Institutional, single-center. PATIENT
POPULATION: Total of 664 eyes with Fuchs endothelial corneal dystrophy (FECD)
scheduled for primary DMEK. INTERVENTION: DMEK. MAIN OUTCOME MEASURES: The
incidence rate of lamellar DM splitting in the recipients' eyes; ultrastructural
alterations of stripped DM specimens (transmission electron microscopy);
preoperative best-corrected visual acuity (BCVA), central corneal thickness
(CCT), and prevalence of diabetes mellitus. RESULTS: Sixty-three of 664 eyes
(9.5%) with FECD showed lamellar splitting of DM resulting in the dissociation of
2 separate layers. Transmission electron microscopy revealed accumulations of
banded and wide-spaced collagen between the thicker posterior banded layer and
the thin anterior banded layer, which is adhesive to the corneal stroma. Lamellar
splitting occurred along these abnormal collagen inclusions, demarcating the
borderline between both layers of DM. CONCLUSIONS: Lamellar DM splitting occurs
during DM stripping in almost 10% of eyes with FECD. This phenomenon appears to
be caused by abnormal collagenous material deposits at the borderline between
anterior and posterior layers of DM.
PMID- 27609711
TI - Microvesicles from brain-extract-treated mesenchymal stem cells improve
neurological functions in a rat model of ischemic stroke.
AB - Transplantation of mesenchymal stem cells (MSCs) was reported to improve
functional outcomes in a rat model of ischemic stroke, and subsequent studies
suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects
of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from
untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract
(NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract
(SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by
permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE
MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic
brain injury with improved functional recovery. We found similar profiles of key
signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their
similar therapeutic efficacies. Immunohistochemical analyses suggest that brain
extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase
endogenous neurogenesis in the rat brain. We performed mass spectrometry
proteomic analyses and found that the total proteomes of brain-extract-treated
MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV
proteins upregulated by brain extracts tend to be modular for tissue repair
pathways. We suggest that MSC-MV proteins stimulated by the brain
microenvironment are paracrine effectors that enhance MSC therapy for stroke
injury.
PMID- 27609714
TI - Different next generation sequencing platforms produce different microbial
profiles and diversity in cystic fibrosis sputum.
AB - BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized
by recurrent lung infections. Studies of the lung microbiome have shown an
association between decreasing diversity and progressive disease. 454
pyrosequencing has frequently been used to study the lung microbiome in CF, but
will no longer be supported. We sought to identify the benefits and drawbacks of
using two state-of-the-art next generation sequencing (NGS) platforms, MiSeq and
PacBio RSII, to characterize the CF lung microbiome. Each has its advantages and
limitations. METHODS: Twelve samples of extracted bacterial DNA were sequenced on
both MiSeq and PacBio NGS platforms. DNA was amplified for the V4 region of the
16S rRNA gene and libraries were sequenced on the MiSeq sequencing platform,
while the full 16S rRNA gene was sequenced on the PacBio RSII sequencing
platform. Raw FASTQ files generated by the MiSeq and PacBio platforms were
processed in mothur v1.35.1. RESULTS: There was extreme discordance in alpha
diversity of the CF lung microbiome when using the two platforms. Because of its
depth of coverage, sequencing of the 16S rRNA V4 gene region using MiSeq allowed
for the observation of many more operational taxonomic units (OTUs) and higher
Chao1 and Shannon indices than the PacBio RSII. Interestingly, several patients
in our cohort had Escherichia, an unusual pathogen in CF. Also, likely because of
its coverage of the complete 16S rRNA gene, only PacBio RSII was able to identify
Burkholderia, an important CF pathogen. CONCLUSION: When comparing microbiome
diversity in clinical samples from CF patients using 16S sequences, MiSeq and
PacBio NGS platforms may generate different results in microbial community
composition and structure. It may be necessary to use different platforms when
trying to correctly identify dominant pathogens versus measuring alpha-diversity
estimates, and it would be important to use the same platform for comparisons to
minimize errors in interpretation.
PMID- 27609715
TI - Production and evaluation of cytotoxic effects of DT386-BR2 fusion protein as a
novel anti-cancer agent.
AB - The aim of this study was to produce a fusion protein consisting of the catalytic
and translocation domains of diphtheria toxin fused to BR2, a cancer specific
cell penetrating peptide, and evaluation of its cytotoxic effects for targeted
eradication of cancer cells. For this purpose, The DT386-BR2 structure was
predicted using Modeller 9.14 and the best predicted model was selected based on
the minimum DOPE score. A synthetic gene encoding DT386-BR2 was cloned in pET28a
expression vector, expressed and purified by affinity chromatography. SDS-PAGE
and Western blotting confirmed the expression of the DT386-BR2 fusion protein by
revealing a band of about 47kDa after the induction of the expression. Finally,
the purified protein was subjected to MTT assay for evaluation of its cyto-lethal
effects on cancer and normal cell lines. Statistical analysis showed significant
reduction in survival percent of HeLa and MCF-7 cancer cells in comparison to
negative control (PBS), while the cytotoxic effect was not significant on the
normal cells, i.e. HUVEC and HEK 293. The IC50 of DT386-BR2 for HeLa and MCF-7
was about 0.55 and 2.08MUg/ml, respectively. In conclusion, the production and
purification of DT386-BR2 fusion protein was successfully achieved and its
cytotoxic effects on the studied cancer cell lines was established. The promising
cytotoxic effects of this newly constructed fusion protein made it a suitable
candidate for targeted therapy of cancer, and further in vitro and in vivo
studies on this fusion protein is underway.
PMID- 27609716
TI - Traversing boundaries: thrombus in transit with paradoxical embolism.
AB - A 72-year-old male is diagnosed with paradoxical embolus after he presented with
concurrent deep vein thrombosis, stroke, and multiple arterial emboli in the
presence of a patent foramen ovale (PFO). Paradoxical embolus requires the
passage of a thrombus from the venous into the arterial circulation through a
right-to-left shunt leading to systemic embolism. But, despite the high incidence
of PFO (27.3% across all age groups by autopsy), paradoxical embolism (PDE) is
uncommon, representing <2% of all arterial emboli. We present a case report where
a thrombus has been directly observed passing through the PFO during an
echocardiogram study; thus, clearly delineating the true cause of multiple
thromboemboli and stoke in our patient. Subsequent Transesophageal
Echocardiography (TEE) also interestingly showed the thrombus in transit in the
aorta and pulmonary artery.
PMID- 27609717
TI - Prolonged cardiac arrest complicating a massive ST-segment elevation myocardial
infarction associated with marijuana consumption.
AB - Recreational substance use and misuse constitute a major public health issue. The
annual rate of recreational drug overdose-related deaths is increasing
exponentially, making unintentional overdose as the leading cause of injury
related deaths in the United States. Marijuana is the most widely used
recreational illicit drug, with approximately 200 million users worldwide.
Although it is generally regarded as having low acute toxicity, heavy marijuana
usage has been associated with life-threatening consequences. Marijuana is
increasingly becoming legal in the United States for both medical and
recreational use. Although the most commonly seen adverse effects resulting from
its consumption are typically associated with neurobehavioral and
gastrointestinal symptoms, cases of severe toxicity involving the cardiovascular
system have been reported. In this report, the authors describe a case of
cannabis-associated ST-segment elevation myocardial infarction leading to a
prolonged cardiac arrest.
PMID- 27609718
TI - An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT)-type
lymphoma.
AB - MALT: Mucosa-associated lymphoid tissue (MALT)-type lymphoma is a relatively rare
disease; nevertheless, it is the third most common lymphoma type, accounting for
5-7% of all non-Hodgkin lymphomas. Case series and retrospective analysis
published in the literature have suggested that extra gastrointestinal (GI) MALT
type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI
tract. We report the case of a healthy, 64-year-old Caucasian male who presented
with progressive fatigue, non-productive cough, and worsening exertional
shortness of breath for 3 months who was subsequently diagnosed with gastric
extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis
to the lung (bronchi) based on biopsy reports. CASE PRESENTATION: A 64-year-old
Caucasian male presented to the emergency room complaining of progressive fatigue
for 3 months which had progressed to the point of hindering his usual activities
of daily living (ADL). He had recently visited his primary care provider for
evaluation of a non-productive cough and exertional shortness of breath. A chest
radiography obtained at the time showed bilateral infiltrates. He was then
treated for atypical pneumonia but his symptoms unfortunately did not improve.
Initial investigations in the emergency room revealed severe anemia and a
positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an
irregular gastric mass. Gastric and transbronchial biopsies were suggestive of
extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the
bronchi. He was treated symptomatically with transfusion of packed red blood
cells (PRBC) and intravenous iron followed by radiotherapy. Helicobacter pylori
infection was ruled out eliminating the possibility of treating him with
eradication therapy. CONCLUSION: Although the stomach is the most common and most
extensively studied site of involvement of MALT lymphomas, they can also emerge
in many other locations. MALT lymphomas have a high tendency to disseminate to
other sites; therefore, extensive staging may be necessary to look for suspicious
lesions.
PMID- 27609719
TI - Thyroid storm presenting as psychosis: masked by diabetic ketoacidosis.
AB - INTRODUCTION: While extremely uncommon, diabetic ketoacidosis (DKA) and thyroid
storm (TS) are endocrine emergencies that can coexist. We describe a case with a
confounding clinical presentation that identifies these two emergencies within
the setting of sepsis and influenza. CASE: A 69-year-old diabetic female was
found by the paramedic staff to be disoriented. She demonstrated tachycardia and
had a foul-smelling abdominal wound. Laboratory evaluation revealed DKA,
leukocytosis, influenza B, and urinary tract infection. After appropriate
management in the intensive care unit, the DKA resolved the following morning.
However, the patient developed a fever, and her psychosis became more pronounced.
Extensive analysis was performed but did not explain her mental status. The
patient was found to have thyroid stimulating hormone of 0.06 mIU/mL, free T4
(thyroxine) of 2.38 ng/dL, and total T3 (triiodothyronine) of 72 ng/dL. Based on
the Burch and Wartofsky criteria (score of 65), TS was diagnosed. Based on more
recent diagnostic criteria suggested by Akamizu et al., the patient met criteria
for TS grade 1. Within several hours of initiating treatment, the patient's
mental state and tachycardia improved, and her psychosis resolved by the third
day. CONCLUSION: This case highlights the importance of recognizing the clinical
diagnosis of TS, as the magnitude of thyroid hormone derangements may not
correlate with clinical severity. While rare, DKA and TS can simultaneously occur
and are associated with increased morbidity and mortality if not promptly
recognized and treated.
PMID- 27609720
TI - The alarming reality of medication error: a patient case and review of
Pennsylvania and National data.
AB - CASE DESCRIPTION: A 71-year-old female accidentally received thiothixene
(Navane), an antipsychotic, instead of her anti-hypertensive medication
amlodipine (Norvasc) for 3 months. She sustained physical and psychological harm
including ambulatory dysfunction, tremors, mood swings, and personality changes.
Despite the many opportunities for intervention, multiple health care providers
overlooked her symptoms. DISCUSSION: Errors occurred at multiple care levels,
including prescribing, initial pharmacy dispensation, hospitalization, and
subsequent outpatient follow-up. This exemplifies the Swiss Cheese Model of how
errors can occur within a system. Adverse drug events (ADEs) account for more
than 3.5 million physician office visits and 1 million emergency department
visits each year. It is believed that preventable medication errors impact more
than 7 million patients and cost almost $21 billion annually across all care
settings. About 30% of hospitalized patients have at least one discrepancy on
discharge medication reconciliation. Medication errors and ADEs are an
underreported burden that adversely affects patients, providers, and the economy.
CONCLUSION: Medication reconciliation including an 'indication review' for each
prescription is an important aspect of patient safety. The decreasing frequency
of pill bottle reviews, suboptimal patient education, and poor communication
between healthcare providers are factors that threaten patient safety. Medication
error and ADEs cost billions of health care dollars and are detrimental to the
provider-patient relationship.
PMID- 27609721
TI - Solitary parotid metastasis 8 years after a nephrectomy for renal cell carcinoma.
AB - Renal cell carcinoma is a common cancer, known for its aggressive behavior and
ability to metastasize nearly every organ system in the body. While the cancer
commonly spreads to a select few organs and metastasis usually develops within 5
years of diagnosis, there have been numerous case reports of atypical sites of
metastasis and cases of relapse up to decades after treatment. We present a case
a 65-year-old male who presented with right preauricular swelling 8 years after
the initial diagnosis and right nephrectomy for clear cell renal cell cancer. We
take a look at previous case reports with similar presentations.
PMID- 27609722
TI - Melanoma with gastric metastases.
AB - An 81-year-old woman with a history of malignant melanoma who presented with
dyspnea and fatigue was found to have metastases to the stomach detected on
endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare
occurrence, and it is often not detected until autopsy because of its non
specific manifestations.
PMID- 27609723
TI - Defining excellence: next steps for practicing clinicians seeking to prevent
diagnostic error.
AB - The Institute of Medicine (IOM) released its report on diagnostic errors in
September, 2015. The report highlights the urgency of reducing errors and calls
for system-level intervention and changes in our basic clinical interactions.
Using the report's controversial definition of diagnostic error as a starting
point, we introduce the issues and the potential impact on practicing physicians.
We report a case used to illustrate this in an academic conference. Finally, we
turn to the challenge of integrating these ideas into the traditional peer-review
process. We argue that the medical community must evolve from understanding
diagnostic failures to redesigning the diagnostic process. We should see errors
as steps toward diagnostic excellence and reliable processes that minimize the
risk of mislabeling and harm.
PMID- 27609724
TI - Omnious T-wave inversions: Wellens' syndrome revisited.
AB - Wellens' syndrome is characterized by T-wave changes in electrocardiogram (EKG)
during pain-free period in a patient with intermittent angina chest pain. It
carries significant diagnostic and prognostic value because this syndrome
represents a pre-infarction stage of coronary artery disease involving proximal
left anterior descending (LAD) artery, which can subsequently lead to extensive
anterior myocardial infarctions (MIs) and even death without coronary
angioplasty. Therefore, it is crucial for every physician to recognize EKG
features of Wellens' syndrome in order to take appropriate immediate intervention
to reduce mortality and morbidity for MI. Here, we report a case of an overweight
man with 35 pack-year of smoking history who presented to Easton Hospital with
intermittent pressing chest pain of 5/6 times within 10 day-period and was found
to have type A Wellens' sign, which was biphasic T-waves in precordial leads V2
and V3 during pain-free period with no cardiac enzymes elevation. He was given
therapeutic lovenox and subsequently underwent coronary angioplasty and had 95
99% occlusion in proximal LAD artery. The unique feature of our case was that
Wellens' type B EKG changes were seen after reduction of stenosis with LAD artery
stent, which was likely explained by the reperfusion of the ischemic myocardium.
Therefore, it is important for physicians to recognize EKG features of Wellens'
syndrome in order to take appropriate therapy to reducing mortality and morbidity
form impending MI.
PMID- 27609725
TI - Inappropriate use of commercial Antinuclear Antibody Testing in a community-based
US hospital: a retrospective study.
AB - Healthcare providers use antinuclear antibodies (ANAs) to screen and diagnose
patients with autoimmune diseases. In the recent years, commercial multiplex ANA
kits have emerged as a convenient and fast diagnostic method. Diagnostic testing
should follow sequenced algorithms: initial screen followed by specific antibody
analysis. Second-level testing as an initial screen for autoimmune disease is
inappropriate. We reviewed 68 patients with ANA comprehensive panels over a 6
month period from May 2015 to October 2015. We assessed appropriateness and
estimated incurred losses from inappropriate testing. We found 92.6% (63 out of
68) of the ANA comprehensive panel results to be negative. Incurred losses from
inappropriate ANA comprehensive panel testing were $66,000. Physicians should
become familiar with ANA-sequenced diagnostic algorithms to avoid unnecessary
higher level testing.
PMID- 27609726
TI - Strongyloidiasis in the immunocompetent: an overlooked infection.
AB - Strongyloidiasis is a parasitic infestation caused by Strongyloides stercoralis.
Most cases are asymptomatic; however, symptomatic patients may present with a
wide range of non-specific cutaneous, pulmonary, or gastrointestinal symptoms
posing a diagnostic dilemma and delay in diagnosis. We report a case of a 58-year
old female who presented with months of generalized pruritus and abdominal
discomfort along with persistent eosinophilia due to strongyloidiasis, which
completely resolved with treatment.
PMID- 27609727
TI - Gastrointestinal perforation: relation to corticosteroid use and COPD - a case
report.
AB - Gastrointestinal perforations are a complication of 2-10% of duodenal ulcers.
There are a variety of etiologies associated with duodenal ulcer formation and
its complications. Corticosteroid use is associated with an increased risk of
duodenal ulcer perforation, with the first documented case in 1950. Other
important medications associated with perforation include NSAIDS and opioids.
Beyond medication, one of the most common disease processes, chronic obstructive
pulmonary disease (COPD), has been found to be associated with peptic ulcer
disease. Up to 30% of COPD patients have been found to have peptic ulcers, and
COPD frequency in peptic ulcer disease is 2-3 times the general population. We
herein present a case of an acute duodenal ulcer perforation in a patient
receiving corticosteroid treatment for an acute COPD exacerbation.
PMID- 27609729
TI - Relationship of symptoms with sleep-stage abnormalities in obstructive sleep
apnea-hypopnea syndrome.
AB - BACKGROUND: Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)
present with a variety of sleep-related symptoms. In polysomnography, sleep
architecture is almost always abnormal, but it is not known which of the sleep
stage abnormalities are related to symptoms. Finding key sleep-stage abnormality
that cause symptoms may be of therapeutic importance to alleviate symptoms. So
far the mainstay of treatment is continuous positive airway pressure (CPAP)/bi
level positive airway pressure (BIPAP) therapy, but many patients are non
compliant to it. Correcting the sleep-stage abnormality that cause symptoms by
pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy. METHODS: A
cross-sectional study. Adult subjects who attended a sleep laboratory for
diagnostic polysomnography for a period of 1 month were recruited consecutively.
OSAHS was diagnosed using American Academy of Sleep Medicine criteria. Subjects
filled a questionnaire for symptoms prior to polysomnography. RESULTS: Thirty
subjects, of whom 83.3% were obese, met diagnostic criteria, with males
constituting 46.7% and females constituting 53%. Mean age was 53.40+/-11.60
years. Sleep architecture comprised N1 19.50+/-19.00%, N2 53.93+/-13.39%, N3
3.90+/-19.50%, and rapid eye movement 8.92+/-6.21%. Excessive fatigue or
sleepiness, waking up tired, falling asleep during the day, trouble paying
attention, snoring and insomnia were significantly related to decreased N3 sleep.
CONCLUSIONS: Most of the symptoms in OSAHS in adults are related to decreased
stage N3 sleep. If confirmed by larger controlled studies, correcting N3 sleep
deficiency by pharmacotherapy may become an important adjunct to CPAP/BIPAP
therapy to alleviate symptoms.
PMID- 27609728
TI - In the era of corona virus: health care professionals' knowledge, attitudes, and
practice of hand hygiene in Saudi primary care centers: a cross-sectional study.
AB - BACKGROUND: Hand hygiene is one of the essential means to prevent the spread of
infections. The aim of this study was to assess the knowledge, attitudes, and
practice (KAP) of hand hygiene in primary care settings. METHODS: A cross
sectional study using a self-reported questionnaire was conducted in primary care
settings located in Riyadh, Kingdom of Saudi Arabia, under the service of King
Abdulaziz Medical City (KAMC). The Institutional Review Board of KAMC Research
Centre approved the study. Data were analyzed using IBM SPSS software. RESULTS: A
total of 237 participants were included in the analysis. Participants who
received hand hygiene training within the last 3 years (2012-2014) scored higher
on a knowledge scale. Generally, there was an overall positive attitude from
participants toward hand hygiene practice. In total, 87.54% acknowledged that
they routinely used alcohol-based hand rub, 87.4% had sufficiently decontaminated
hands even under high work pressure, and 78.6% addressed that this practice was
not affected by less compliant colleagues. CONCLUSION: Practicing hand hygiene
was suggested to be influenced by variables related to the environmental context,
social pressure, and individual attitudes toward hand hygiene. We believe that
addressing beliefs, attitudes, capacity, and supportive infrastructures to
sustain hand-hygiene routine behaviors are important components of an
implementation strategy in enhancing health care workers' KAP of hand hygiene.
PMID- 27609730
TI - An improbable and unusual case of thrombotic thrombocytopenia purpura.
AB - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency
which may be difficult to recognize given the wide spectrum in which it presents.
A delay in treatment may be catastrophic as untreated cases of TTP have a
mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and
its range of presenting symptoms, we present our unusual case of TTP in a post
splenectomy patient with early treatment and positive outcome. This case
describes a 54-year-old female who presented with hematuria and gingival
bleeding, followed by the development of a bilateral lower extremity petechial
rash. Her past medical history was significant for multiple episodes of TTP, the
last of which resulted in a splenectomy and a 20-year history of remission
thereafter. On exam, she was alert, well appearing, and neurologically intact.
Her only significant finding was a bilateral lower extremity petechial rash.
Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate
dehydrogenase, and a decreased haptoglobin. Peripheral smear showed
poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was
promptly initiated, her platelets were monitored closely, and she underwent
urgent therapeutic plasma exchange. Due to the risk of significant morbidity and
mortality that may result from delayed treatment of TTP as well as the
significant variations of presentation, TTP requires a consistently high index of
suspicion. Our patient suffered multiple relapses of TTP within a 30-year span,
underwent splenectomy in early adulthood, and presented with atypical symptoms
during her most recent relapse illustrating how persistent TTP can be as well as
how unusually it may present. Providers should be aware of the vast spectrum of
presentation and remember that TTP may recur following splenectomy despite
prolonged remission.
PMID- 27609731
TI - Endocarditis due to Gemella haemolysans in a newly diagnosed multiple myeloma
patient.
AB - An 87-year-old Caucasian woman with hypertension, diabetes mellitus type 2, and
COPD was admitted with 1-week duration of back pain and weight gain. The physical
examination revealed jugular venous distention, rales in the left lower lung
field, and severe pitting edema over lower extremities. As workup for
leukocytosis, blood cultures grew Gemella haemolysans. Subsequently, a
transthoracic echocardiogram revealed vegetation on the non-coronary aortic
leaflet and mild aortic stenosis. She was treated with ampicillin and gentamicin.
After further investigation, the patient was diagnosed with plasma cell myeloma,
the monoclonal lambda type. This is the first reported case of G. haemolysans
endocarditis in a multiple myeloma patient.
PMID- 27609732
TI - A review of treatment options for Graves' disease: why total thyroidectomy is a
viable option in selected patients.
AB - Graves' disease is the most common cause of hyperthyroidism. If left untreated,
patients may have multiple systemic complications such as cardiac, reproductive,
and skeletal disease. Thionamides, such as methimazole and propylthiouracil, and
I(131) iodine ablation are the most commonly prescribed treatment for Graves'
disease. Total thyroidectomy is often overlooked for treatment and is usually
only offered if the other options have failed. In our case, we discuss a patient
who was admitted to our medical center with symptomatic hyperthyroidism secondary
to long-standing Graves' disease. She had a history of non-compliance with
medications and medical clinic follow-up. The risks and benefits of total
thyroidectomy were explained and she consented to surgery. A few months after the
procedure, she was biochemically and clinically euthyroid on levothyroxine. She
had no further emergency room visits or admissions for uncontrolled thyroid
disease. Here we review the advantages and disadvantages of the more typically
prescribed treatments, thionamides and I(131)iodine ablation. We also review the
importance of shared decision making and the benefits of total thyroidectomy for
the management of Graves' disease. Given the improvement in surgical techniques
over the past decade and a significant reduction of complications, we suggest
total thyroidectomy be recommended more often for patients with Graves' disease.
PMID- 27609733
TI - Bilateral adrenal hemorrhage in polycythemia vera.
AB - Bilateral adrenal hemorrhage (BAH) is a rare complication typically seen in
critically ill patients, which can lead to acute adrenal insufficiency and death
unless it is recognized promptly and treated appropriately. We describe the case
of a 64-year-old man with polycythemia vera found to be unresponsive with fever,
hypotension, tachycardia, and hypoglycemia. Electrocardiogram showed ST-elevation
with elevated troponin, hemoglobin, prothrombin time, and partial thromboplastin
time. He required aggressive ventilator and vasopressor support. Despite primary
coronary intervention, he remained hypotensive. Random cortisol level was low. He
received stress dose hydrocortisone with immediate hemodynamic stability. BAH was
highly suspected and was confirmed by non-contrast abdominal computed tomography.
Prompt recognition and timely initiated treatment remain crucial to impact the
mortality associated with acute adrenal insufficiency.
PMID- 27609734
TI - Life-threatening hemorrhage from acquired hemophilia A as a presenting
manifestation of prostate cancer.
AB - Acquired factor VIII deficiency (acquired hemophilia A) is a rare condition
characterized by the acquisition of autoantibodies that affect the clotting
activity of factor VIII (fVIII). The most common manifestation in affected
patients is a hemorrhagic diathesis. This disorder is associated with autoimmune
diseases, pregnancy, postpartum period, drugs, and malignancy. Management of this
condition begins with attempts to arrest an acute bleed based on the site and
severity of bleeding and inhibitor titer. The next priority is eradication of the
fVIII antibodies using immunosuppressive therapies. We report the case of a 66
year-old male who presented with spontaneous right thigh hematoma with prolonged
activated partial prothrombin time and normal prothrombin time. Mixing studies
confirmed the presence of an inhibitor. Further investigation for the underlying
etiology of acquired hemophilia A leads to diagnosis of prostate cancer.
Treatment consisted of bypassing agents including activated factor VII and
activated prothrombin plasma concentrate to arrest the bleeding. Steroids and
cyclophosphamide were added to suppress the fVIII inhibitors. Concomitant
treatment of locally advanced prostate cancer with chemotherapy confirmed the
eradication of the inhibitors. To our knowledge, this is the first reported case
of prostate cancer diagnosed and treated simultaneously with acquired hemophilia
A resulting in favorable patient outcome.
PMID- 27609736
TI - Utilization of 4T score to determine the pretest probability of heparin-induced
thrombocytopenia in a community hospital in upstate New York.
AB - BACKGROUND: Thrombocytopenia is common in hospitalized patients. Heparin-induced
thrombocytopenia (HIT) is a life-threatening condition which can lead to
extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by
4T score and immunoassays through testing for anti-PF4/heparin antibodies.
Clinical practice guidelines published by the American Society of Hematology in
2013 recommended use of the 4T score before ordering the immunoassays as a
measure of pretest probability. The purpose of this study was to evaluate the
utilization of 4T score before ordering anti-PF4/heparin antibodies at Unity
Hospital. METHODS: We did a retrospective chart review for patients who are 18
years or older, admitted to Unity Hospital between July 1, 2013, and December 31,
2014, and had anti-PF4/heparin antibodies ordered. Subjects who had prior history
of HIT or had end-stage renal disease on hemodialysis were excluded. After
calculating 4T score retrospectively, we calculated the proportion of patients
who had 4T score documented prior to ELISA testing and proportion of ELISA tests,
which were not indicated due to a 4T score less than or equal to 3 using Minitab
16. RESULTS: Review of 123 patients, with an average age of 69.4 years, showed
that testing was indicated in 18 patients. Six subjects had positive results, and
testing was indicated in all of them. 4T score was documented in three patients.
This quality improvement study showed that 4T score documentation rate at Unity
Hospital is 2.4%. Anti-PF4/heparin antibody testing was indicated in 14.6%. This
test is being overused in thrombocytopenia work up at Unity Hospital, costing
$9,345. The topic was reviewed for residents. A prompt and calculator for 4T
score were added to electronic medical records before ordering the test as a step
to improve high value care.
PMID- 27609735
TI - A case of asymptomatic pancytopenia with clinical features of hemolysis as a
presentation of pernicious anemia.
AB - Pernicious anemia is an autoimmune disease with a variety of clinical
presentations. We describe a case of pernicious anemia presenting with
pancytopenia with hemolytic features. Further workup revealed very low vitamin
B12 levels and elevated methylmalonic acid. It is important for a general
internist to identify pernicious anemia as one of the cause of pancytopenia and
hemolytic anemia to avoid extensive workup. Pernicious anemia can present
strictly with hematological abnormalities without neurological problems or vice
versa as in our case.
PMID- 27609737
TI - Hybrid Repair of Thoracoabdominal Aortic Aneurysms Is a Durable Option for High
Risk Patients in the Endovascular Era.
AB - OBJECTIVE: To report our long-term experience in using the hybrid technique in
complex thoracoabdominal aortic aneurysms (TAAAs). METHODS: Between March 2005
and September 2013, 10 patients with TAAA underwent hybrid procedures with open
renovisceral revascularization and thoracoabdominal aortic endografting. Patients
were analyzed retrospectively. RESULTS: Six men and 4 women with a mean age of 66
years (range 54-81 years) were treated electively during the study period. All 4
visceral vessels were revascularized in 8 patients, whereas 1 patient underwent 3
vessel revascularization and another 2-vessel revascularization. The primary
technical success rate was 100%. Eight of the procedures were single staged, and
the 2 most recent cases were performed in 2 stages. Perioperative and 30-day
mortality was 0%. The mean follow-up was 55 months (4-133 months). None of the
patients died due to aortic complications. Major complications included
paraplegia (10%, n = 1) and bowel ischemia (n = 1). Postoperative cerebrospinal
fluid (CSF) pressure and mean arterial pressure measurements were systematically
monitored and corrected. The CSF drainage solved another 4 cases of paraparesis.
Three patients required postoperative dialysis, but none of them required
permanently. Postoperative spinal cord ischemia and renal complications
accumulated in extensive TAAA cases. One renal graft was occluded 45 days after
the initial procedure but was successfully treated with thrombolysis. One type I
and 1 type III endoleak were noted and successfully treated with an additional
stent graft. Two cases of type II endoleak were detected-one with a growing
aneurysm sac was treated successfully and another showed no growth and further
procedures were abandoned after 2 embolization attempts. In long-term follow-up,
90% of the aneurysms showed shrinkage by a mean of 23 mm (range 7-45 mm).
CONCLUSION: The results of hybrid repair on high-risk patients with complex TAAAs
are encouraging, and this approach is a valuable alternative when branched and
fenestrated endovascular techniques are not considered an option.
PMID- 27609739
TI - Best practice advice on the 10-Group Classification System for cesarean
deliveries.
PMID- 27609738
TI - Development and Usability of REACH: A Tailored Theory-Based Text Messaging
Intervention for Disadvantaged Adults With Type 2 Diabetes.
AB - BACKGROUND: Among adults with type 2 diabetes mellitus (T2DM), adherence to
recommended self-care activities is suboptimal, especially among racial and
ethnic minorities with low income. Self-care nonadherence is associated with
having worse glycemic control and diabetes complications. Text messaging
interventions are improving the self-care of adults with T2DM, but few have been
tested with disadvantaged populations. OBJECTIVE: To develop Rapid
Education/Encouragement And Communications for Health (REACH), a tailored, text
messaging intervention to support the self-care adherence of disadvantaged
patients with T2DM, based on the Information-Motivation-Behavioral skills model.
We then tested REACH's usability to make improvements before evaluating its
effects. METHODS: We developed REACH's content and functionality using an
empirical and theory-based approach, findings from a previously pilot-tested
intervention, and the expertise of our interdisciplinary research team. We
recruited 36 adults with T2DM from Federally Qualified Health Centers to
participate in 1 of 3 rounds of usability testing. For 2 weeks, participants
received daily text messages assessing and promoting self-care, including
tailored messages addressing users' unique barriers to adherence, and weekly text
messages with adherence feedback. We analyzed quantitative and qualitative user
feedback and system-collected data to improve REACH. RESULTS: Participants were,
on average, 52.4 (SD 9.5) years old, 56% (20/36) female, 63% (22/35) were a
racial or ethnic minority, and 67% (22/33) had an income less than US $35,000.
About half were taking insulin, and average hemoglobin A1c level was 8.2% (SD
2.2%). We identified issues (eg, user concerns with message phrasing, technical
restrictions with responding to assessment messages) and made improvements
between testing rounds. Overall, participants favorably rated the ease of
understanding (mean 9.6, SD 0.7) and helpfulness (mean 9.3, SD 1.4) of self-care
promoting text messages on a scale of 1-10, responded to 96% of assessment text
messages, and rated the helpfulness of feedback text messages 8.5 (SD 2.7) on a
scale of 1-10. User feedback led to refining our study enrollment process so that
users understood the flexibility in message timing and that computers, not
people, send the messages. Furthermore, research assistants' feedback on the
enrollment process helped improve participants' engagement with study procedures.
CONCLUSIONS: Testing technology-delivered interventions with disadvantaged adults
revealed preferences and concerns unique to this population. Through iterative
testing and multiple data sources, we identified and responded to users'
intervention preferences, technical issues, and shortcomings in our research
procedures.
PMID- 27609740
TI - Female genital mutilation among mothers and daughters in Harar, eastern Ethiopia.
AB - OBJECTIVE: To assess the practice of female genital mutilation (FGM) among
mothers and daughters, and to investigate sociodemographic factors influencing
the practice of FGM in Harar, Ethiopia. METHODS: A community-based cross
sectional study was conducted among women aged 15 years or older who had at least
one living daughter younger than 12 years via the Harar Health and Demographic
Surveillance System 2013. Data were collected through face-to-face interviews.
The practice of FGM was compared between mothers and their daughters. Whether the
daughter had undergone FGM was included as an outcome variable in bivariate and
multivariate analyses. RESULTS: Among 842 mothers, 669 (79.5%) reported that they
had undergone FGM themselves, and 160 (19.0%) that their daughter had undergone
FGM. Traditional practitioners were said to be the major performers of FGM by 151
(94.4%) mothers. Mothers whose daughter was mutilated mentioned social acceptance
(144 [90.0%] women) and better marriage prospects (96 [60.0%]) as the major
benefits. Genital mutilation of daughters was significantly associated with
maternal age, education to grade 1-4, and FGM experience. Amhara ethnic origin
was significantly associated with a reduced likelihood of FGM among daughters.
CONCLUSION: Over one generation, the incidence of FGM has reduced. Increasing
advocacy against FGM and enforcement of law should be emphasized.
PMID- 27609741
TI - Associations between serum placental leucine aminopeptidase and pregnancy
outcomes.
AB - OBJECTIVE: To investigate the association between serum concentrations of
placental leucine aminopeptidase (P-LAP) and hypertensive disorders in pregnancy
(HDP), gestational diabetes mellitus (GDM), and perinatal mortality. METHODS: In
a prospective study, women with singleton pregnancies and affected by HDP, GDM,
or fetal death, and those who were healthy, were enrolled at Shenzhen Seventh
People's Hospital, Shenzhen, China, between January 2014 and July 2015. Serum P
LAP concentrations at delivery/fetal death were compared among the groups. The
predictive value of serum P-LAP levels in fetal death was evaluated. RESULTS:
Serum P-LAP concentrations were (mean +/- SEM) 74.02 +/- 8.45 U/L in the HDP
group (n=38), 72.57 +/- 12.03 U/L in the GDM group (n=35), and 3.76 +/- 3.02 U/L
in the fetal death group (n=14), all of which were significantly lower than the
mean concentration of 107.11 +/- 30.68 U/L in the control group (n=30; P=0.031,
P=0.042, and P<0.001, respectively). On the basis of the receiver operating
characteristic curve, low serum P-LAP levels had high sensitivity and specificity
for predicting fetal death (100% and 78.9%, respectively, for a serum P-LAP
cutoff of 47.07 U/L). CONCLUSION: Serum P-LAP levels were reduced among patients
with HDP and GDM, and extremely low among patients affected by fetal death. Serum
P-LAP is potentially a viable predictor of fetal death.
PMID- 27609743
TI - Tunisian experience of low-cost self-created transobturator tape for the
treatment of stress urinary incontinence.
PMID- 27609742
TI - An unusual case of abnormal uterine bleeding due to classical Hodgkin lymphoma
identified by endometrial biopsy.
PMID- 27609745
TI - Volume and social context of physical activity in association with mental health,
anxiety and depression among youth.
AB - There is growing interest in physical activity (PA) to prevent mental disorders
in youth. However, few studies examine the association between PA and mental
health. Further, how PA volume and context relate to mental health and mental
disorders remains unclear, especially among youth in transition to adulthood.
This study examined the cross-sectional associations among PA volume and context,
mental health, and symptoms of anxiety and depression in post-secondary students.
A total of 1527 post-secondary students (97.4% were age 16-24years) recruited in
a CEGEP in Quebec, Canada completed a self-report questionnaire during class-time
in October 2013. Multivariate linear regression was used to model the
associations between PA volume and context and mental health, anxiety and
depression controlling for sex, age and perceived socioeconomic status. Volume of
moderate-to-vigorous leisure time PA (MVPA) was positively associated with mental
health (beta (95% CI)=0.072 (0.045, 0.099)) and inversely associated with
symptoms of anxiety (-0.011 (-0.020, -0.001)) and depression (-0.010 (-0.017,
0.003)). Volume including all PA intensities was associated with mental health
(0.052 (0.028, 0.076)). After controlling for PA volume, active youth involved in
team sports had better mental health than those who engaged in PA individually.
PA volume and the social context of PA are independently associated with mental
health among youth. MVPA is inversely associated with anxiety and depressive
symptoms.
PMID- 27609746
TI - The effect of hematocrit and hemoglobin on the risk of ischemic heart disease: A
Mendelian randomization study.
AB - Hematocrit and hemoglobin affect viscosity, and have been considered as risk
factors for ischemic heart disease (IHD), although observations are inconsistent;
randomized controlled trials targeting hematocrit or hemoglobin have not been
definitive. To clarify their role, the risk of IHD was assessed according to
genetically determined hematocrit and hemoglobin. We applied single nucleotide
polymorphisms (SNPs) strongly determining hematocrit and hemoglobin, from a
genome wide association study, to a large case (64,746) control (130,681) study
of coronary artery disease, CARDIoGRAMplusC4D, to obtain unconfounded estimates
using instrumental variable analysis by combining the Wald estimators for each
SNP taking into account any correlation between SNPs using weighted generalized
linear regression. Hematocrit was positively associated with IHD, odds ratio (OR)
1.07 per %, 95% confidence interval (CI) 1.03 to 1.11, before and after excluding
SNPs from gene regions directly functionally relevant to IHD. However, hematocrit
was not associated with IHD (OR 0.99, 0.94 to 1.04) after also excluding SNPs
associated with lipids at genome wide significance. Hemoglobin was not associated
with IHD (OR 1.06 per g/dL, 0.97 to 1.15) which was similar (OR 1.02, 0.94 to
1.11) after excluding SNPs from gene regions directly functionally relevant to
IHD. Hemoglobin was negatively associated with IHD after also excluding SNPs
associated with lipids at genome wide significance (OR 0.86, 0.78 to 0.94). In
conclusion, hematocrit shares genetic determinants with IHD, but whether the
genes contribute to IHD via hematocrit or other mechanisms is not entirely clear.
Higher Hemoglobin is unlikely to cause IHD.
PMID- 27609744
TI - Where Latin Americans are physically active, and why does it matter? Findings
from the IPEN-adult study in Bogota, Colombia; Cuernavaca, Mexico; and Curitiba,
Brazil.
AB - Latin America (LA) has a unique structural, political, cultural and social
environment. This study aimed to identify the places where Latin American adults
are physically active; and to determine the association of using public- and
restricted-access places with physical activity (PA). We used data from the
International PA Environment Network study in Bogota, Colombia (n=1000,
accelerometry=249); Cuernavaca, Mexico (n=677, accelerometry=652); and Curitiba,
Brazil (n=697, accelerometry=331) (2010-2011). Walking and moderate-to-vigorous
PA for leisure were measured with the International Physical Activity
Questionnaire. Overall PA and PA within 10-minute bouts were measured with
accelerometers. Participants reported use of public- and restricted-access places
for PA. Mixed-effects regression models were used to determine the association of
using public- and restricted-access places with PA. The streets were the most
frequently-reported place for PA, and walking was the most common PA in the
studied places. 'Informal', non-exercise-or-sports places (e.g., shopping malls)
ranked high for use for PA in Bogota and Cuernavaca. In Curitiba, use of 'formal'
places for sports/exercise (e.g., gyms) was more prevalent. Using public-access
places was directly related to walking for leisure in all cities, and to
additional PA outcomes in Bogota and Cuernavaca. In Cuernavaca and Curitiba,
using restricted-access places was also associated with PA. Our study highlights
the importance of public-access places for PA in LA. In some contexts, places for
social interaction may be as important for PA as places for exercise/sport.
Strategies increasing the availability, accessibility and quality of these places
may effectively promote PA in LA.
PMID- 27609748
TI - Placental transmogrification of the lung presenting as progressive symptomatic
bullous emphysema.
PMID- 27609749
TI - Numerous metallic foreign bodies in whole body after acupuncture.
PMID- 27609752
TI - Incidence and predictors of headache relief after endovascular treatment in
patients with unruptured intracranial aneurysms.
AB - Objective Patients with unruptured intracranial aneurysms often present with
headaches. We retrospectively determined the incidence of headache relief in
patients with unruptured intracranial aneurysms after endovascular treatment,
with the main goals of preventing aneurysmal haemorrhage and identifying factors
associated with headache relief in a cohort study. Methods From a cohort of
patients with unruptured intracranial aneurysms who were treated with
endovascular coiling and admitted between January 2012 and December 2014, we
included 123 patients who had headaches and underwent regular follow-up. The
severity of headache was assessed by a quantitative 11-point headache scale for
all patients before and after the endovascular treatment. Headache relief was
defined as a decrease in the headache score. We determined the incidence and
predictors of headache relief using Kaplan-Meier curves and Cox regression
analysis. Results Of the 123 patients with a mean follow-up of 14.1 months (range
1-39 months), 69 had headache relief. The overall cumulative incidence of
headache relief was 62.3% (95% confidence interval (CI) 54.2%, 69.4%). On
multivariate Cox regression analysis, the side of headache ipsilateral to the
aneurysm (adjusted hazard ratio 0.540; 95% CI 0.408, 0.715; P < 0.001) and
aneurysm size (adjusted hazard ratio 1.753; 95% CI 1.074, 2.863; P = 0.025) were
significant predictors of headache relief. Conclusions Endovascular treatment
relieved preoperative headaches for most patients with unruptured intracranial
aneurysms. The side of headache ipsilateral to the aneurysm and aneurysm size >10
mm were significant predictors of headache relief.
PMID- 27609747
TI - Targeting cancer stem cells and signaling pathways by phytochemicals: Novel
approach for breast cancer therapy.
AB - Breast cancer is the most common form of cancer diagnosed in women worldwide and
the second leading cause of cancer-related deaths in the USA. Despite the
development of newer diagnostic methods, selective as well as targeted
chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy,
breast cancer recurrence, metastasis and drug resistance are still the major
problems for breast cancer. Emerging evidence suggest the existence of cancer
stem cells (CSCs), a population of cells with the capacity to self-renew,
differentiate and be capable of initiating and sustaining tumor growth. In
addition, CSCs are believed to be responsible for cancer recurrence, anticancer
drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be
better therapeutic agents for treating breast cancer and control recurrence and
metastasis. Naturally occurring compounds, mainly phytochemicals have gained
immense attention in recent times because of their wide safety profile, ability
to target heterogeneous populations of cancer cells as well as CSCs, and their
key signaling pathways. Therefore, in the present review article, we summarize
our current understanding of breast CSCs and their signaling pathways, and the
phytochemicals that affect these cells including curcumin, resveratrol, tea
polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane,
genistein, indole-3-carbinol, 3, 3'-di-indolylmethane, vitamin E, retinoic acid,
quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin,
celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic
agents for breast cancer treatment and future leads for drug development.
PMID- 27609753
TI - Early experience with the Penumbra SMART coil in the endovascular treatment of
intracranial aneurysms: Safety and efficacy.
AB - BACKGROUND: Penumbra SMART coils differ from traditional microcoils used for
endovascular coil embolization of intracranial aneurysms (IAs) in that they (1)
become progressively softer from their distal to proximal end, rather than being
of uniform stiffness, (2) have a tight conformational structure, and (3) have a
more robust stretch-resistance platform. These properties aid in preventing
microcatheter prolapse and coil herniation during coil deployment and in filling
small pockets of the aneurysm sac. OBJECTIVE/METHODS: To determine the safety and
efficacy of this device, the records of 17 consecutive patients with IAs treated
with SMART coils were retrospectively analyzed. RESULTS: Thirteen female and four
male patients were identified. Eleven patients presented with subarachnoid
hemorrhage, four had recurrent aneurysms, and two had incidentally discovered
aneurysms. Twelve aneurysms (two of which were recurrent) were treated with stand
alone coiling, three were treated with stent-assisted coiling, and two with flow
diversion with adjuvant coiling. Microcatheter prolapse occurred in one case of a
recurrent aneurysm, due to mechanical limitations imposed by a stent placed
during prior coiling. Raymond-Roy Occlusion Classification (RROC) I or II
occlusion was achieved in 12 aneurysms, including all 10 undergoing primary stand
alone coiling. Of the five RROC III occlusions, two were expected given treatment
with flow diversion, while the other three occurred in complex, recurrent
aneurysms. One patient suffered a thromboembolic complication of unclear clinical
significance. CONCLUSIONS: The Penumbra SMART coil is a safe and effective device
for the endovascular treatment of IAs. Follow-up studies are required to
establish long-term results.
PMID- 27609750
TI - Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung
disease: the Multi-Ethnic Study of Atherosclerosis.
AB - BACKGROUND: Adults with interstitial lung disease (ILD) often have serologic
evidence of autoimmunity of uncertain significance without overt autoimmune
disease. We examined associations of rheumatoid arthritis (RA)-associated
antibodies with subclinical ILD in community-dwelling adults. METHODS: We
measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide
antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values
between -600 and -250 Hounsfield units) on cardiac CT in 6736 community-dwelling
US adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured
interstitial lung abnormalities (ILAs) in 2907 full-lung CTs at 9.5-year median
follow-up. We used generalised linear and additive models to examine associations
between autoantibodies and both HAA and ILA, and tested for effect modification
by smoking. RESULTS: In adjusted models, HAA increased by 0.49% (95% CI 0.11% to
0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50% to 1.40%) per RF IgA
doubling. ILA prevalence increased by 11% (95% CI 3% to 20%) per RF IgA doubling.
Smoking modified the associations of both RF IgM and anti-CCP with both HAA and
ILA (interaction p values varied from 0.01 to 0.09). Among ever smokers, HAA
increased by 0.81% (95% CI 0.33% to 1.30%) and ILA prevalence increased by 14%
(95% CI 5% to 24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45%
to 2.18%) and ILA prevalence increased by 13% (95% CI 2% to 24%) per anti-CCP
doubling. Among never smokers, no meaningful associations were detected.
CONCLUSIONS: RA-related autoimmunity is associated with both quantitative and
qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.
PMID- 27609754
TI - Protective effect of Cornus walteri Wangerin leaf against UVB irradiation induced
photoaging in human reconstituted skin.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cornus walteri Wangerin has been used in oriental
traditional medicine for the treatment of antidiarrheal and inflammation. AIM OF
THE STUDY: The efficacy of Cornus walteri Wangerin on skin anti-photoaging was
investigated. MATERIALS AND METHODS: Hydrolyzed Cornus walteri Wangerin leaf was
tested for the anti-photoaging effects against ultraviolet B (UVB)-induced matrix
metalloproteinase (MMP)-1, pro-inflammatory cytokines using human reconstituted
skin (KeraSkinTM-FT) and also tested for elastase activity in vitro. The MMP-1
and pro-inflammatory cytokine levels of the extract were evaluated by enzyme
linked immunosorbent assay (ELISA). RESULTS: The extract of hydrolyzed Cornus
walteri Wangerin leaf (CWE) had the elastase inhibitory activity (IC50:
0.457mg/mL). CWE inhibited MMP-1 expression up to 61% in comparison with the
control group which was not treated using CWE, but exposed to UVB. CWE also
showed an inhibitory effect on releasing pro-inflammatory cytokines (IL-6 and IL
8) in KeraSkinTM-FT (30% and 57% inhibition at dose of 50MUg/mL, respectively).
CONCLUSION: CWE is a promising anti-photoaging agent for the treatment of UVB
induced skin.
PMID- 27609755
TI - Effects of Corticosteroids on Critically Ill Pulmonary Tuberculosis Patients With
Acute Respiratory Failure: A Propensity Analysis of Mortality.
AB - BACKGROUND: We investigated the effects of corticosteroids on the 90-day
mortality outcomes in patients with pulmonary tuberculosis who were admitted to
the intensive care unit (ICU) because of acute respiratory failure (ARF).
METHODS: The medical records of 124 patients who had pulmonary tuberculosis with
ARF and were admitted to the ICU at our tertiary referral center in South Korea
between March 1989 and December 2014 were retrospectively analyzed. The 90-day
mortality rate in this population was analyzed after adjustments with the inverse
probability of treatment weighted (IPTW) method. RESULTS: The mean patient age
was 62 years, and the 90-day mortality rate was 49.2% (61/124). Adjuvant steroids
were used in 70 (56.5%) patients. The 90-day mortality rate was similar
irrespective of corticosteroid use (48.6%, steroid group; 50.0%, nonsteroid
group). The use of adjuvant steroids was not associated with the unadjusted 90
day mortality (odds ratio [OR], 0.94; 95% confidence interval [CI], .46-1.92; P =
.875). In a comparison using an adjusted IPTW approach of the 90-day mortality
between the 2 groups, we found that corticosteroid use was independently
associated with reduced 90-day mortality (OR, 0.47; 95% CI, .22-.98; P = .049).
CONCLUSIONS: The study results showed that corticosteroids could reduce the 90
day mortality rate in critically ill pulmonary tuberculosis patients with ARF.
PMID- 27609757
TI - mtDNA diversity in human populations highlights the merit of haplotype matching
in gene therapies.
AB - STUDY QUESTION: Does mitochondrial DNA (mtDNA) diversity in modern human
populations potentially pose a challenge, via mtDNA segregation, to mitochondrial
replacement therapies? SUMMARY ANSWER: The magnitude of mtDNA diversity in modern
human populations is as high as in mammalian model systems where strong mtDNA
segregation is observed; consideration of haplotype pairs and/or haplotype
matching can help avoid these potentially deleterious effects. WHAT IS KNOWN
ALREADY: In mammalian models, substantial proliferative differences are observed
between different mtDNA haplotypes in cellular admixtures, with larger
proliferative differences arising from more diverse haplotype pairings. If
maternal mtDNA is 'carried over' in human gene therapies, these proliferative
differences could lead to its amplification in the resulting offspring,
potentially leading to manifestation of the disease that the therapy was designed
to avoid-but existing studies have not investigated whether mtDNA diversity in
modern human populations is sufficient to permit significant amplification. STUDY
DESIGN, SIZE, DURATION: This theoretical study used over 7500 human mtDNA
sequences from The National Center for Biotechnology Information (NCBI), a range
of international and British mtDNA surveys, and 2011 census data.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A stochastic simulation approach was
used to model random haplotype pairings from within different regions. In total,
1000 simulated pairings were analysed using the basic local alignment search tool
(BLAST) for each region. Previous data from mouse models were used to estimate
proliferative differences. MAIN RESULTS AND THE ROLE OF CHANCE: Even within the
same haplogroup, differences of around 20-80 single-nucleotide polymorphisms
(SNPs) are common between mtDNAs admixed in random pairings. These values are
sufficient to lead to substantial segregation in mouse models over an organismal
lifetime, even given low starting heteroplasmy, inducing increases from 5% to 35%
over 1 year. Substantial population mixing in modern UK cities increases the
expected genetic differences. Hence, the likely genetic differences between
humans randomly sampled from a population may well allow substantial
amplification of a disease-carrying mtDNA haplotype over the timescale of a human
lifetime. We report ranges and mean differences for all statistics to quantify
uncertainty in our results. LIMITATIONS/REASONS FOR CAUTION: The mapping from
mouse and other mammalian models to the human system is challenging, as
timescales and mechanisms may differ. Reporting biases in NCBI mtDNA data, if
present, may affect the statistics we compute. We discuss the robustness of our
findings in the light of these concerns. WIDER IMPLICATIONS OF THE FINDINGS:
Matching the mtDNA haplotypes of the mother and third-party donor in
mitochondrial replacement therapies is supported as a means of ameliorating the
potentially deleterious results of human mtDNA diversity. We present a chart of
expected SNP differences between mtDNA haplogroups, allowing the selection of
optimal partners for therapies. LARGE SCALE DATA: N/A STUDY FUNDING/COMPETING
INTERESTS: The authors report no external funding sources or conflicts of
interest.
PMID- 27609758
TI - Identification of genes differentially expressed in menstrual breakdown and
repair.
AB - STUDY QUESTION: Does the changing molecular profile of the endometrium during
menstruation correlate with the histological profile of menstruation. SUMMARY
ANSWER: We identified several genes not previously associated with menstruation;
on Day 2 of menstruation (early-menstruation), processes related to inflammation
are predominantly up-regulated and on Day 4 (late-menstruation), the endometrium
is predominantly repairing and regenerating. WHAT IS KNOWN ALREADY: Menstruation
is induced by progesterone withdrawal at the end of the menstrual cycle and
involves endometrial tissue breakdown, regeneration and repair. Perturbations in
the regulation of menstruation may result in menstrual disorders including
abnormal uterine bleeding. STUDY DESIGN, SIZE DURATION: Endometrial samples were
collected by Pipelle biopsy on Days 2 (n = 9), 3 (n = 9) or 4 (n = 6) of
menstruation. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA was extracted from
endometrial biopsies and analysed by genome wide expression Illumina Sentrix
Human HT12 arrays. Data were analysed using 'Remove Unwanted Variation-inverse
(RUV-inv)'. Ingenuity pathway analysis (IPA) and the Database for Annotation,
Visualization and Integrated Discovery (DAVID) v6.7 were used to identify
canonical pathways, upstream regulators and functional gene clusters enriched
between Days 2, 3 and 4 of menstruation. Selected individual genes were validated
by quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 1753 genes
were differentially expressed in one or more comparisons. Significant canonical
pathways, gene clusters and upstream regulators enriched during menstrual
bleeding included those associated with immune cell trafficking, inflammation,
cell cycle regulation, extracellular remodelling and the complement and
coagulation cascade. We provide the first evidence for a role for glutathione
mediated detoxification (glutathione-S-transferase mu 1 and 2; GSTM1 and GSTM2)
during menstruation. The largest number of differentially expressed genes was
between Days 2 and 4 of menstruation (n = 1176). We identified several genes not
previously associated with menstruation including lipopolysaccharide binding
protein, serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPINB3) and
-4 (SERPINB4), interleukin-17C (IL17C), V-set domain containing T-cell activation
inhibitor 1 (VTCN1), proliferating cell nuclear antigen factor (KIAA0101/PAF),
trefoil factor 3 (TFF3), laminin alpha 2 (LAMA2) and serine peptidase inhibitor,
Kazal type 1 (SPINK1). Genes related to inflammatory processes were up-regulated
on Day 2 (early-menstruation), and those associated with endometrial repair and
regeneration were up-regulated on Day 4 (late-menstruation). LIMITATIONS, REASONS
FOR CAUTION: Participants presented with a variety of endometrial pathologies
related to bleeding status and other menstrual characteristics. These variations
may also have influenced the menstrual process. WIDER IMPLICATIONS OF THE
FINDINGS: The temporal molecular profile of menstruation presented in this study
identifies a number of genes not previously associated with the menstrual
process. Our findings provide valuable insight into the menstrual process and may
present novel targets for therapeutic intervention in cases of endometrial
dysfunction. LARGE SCALE DATA: All microarray data have been deposited in the
public data repository Gene Expression Omnibus (GSE86003). STUDY FUNDING AND
COMPETING INTERESTS: Funding for this work was provided by a National Health and
Medical Research Council of Australia (NHMRC) Project Grant APP1008553 to M.H.,
P.R. and J.G. M.H. is supported by an NHMRC Practitioner Fellowship. P.P. is
supported by a NHMRC Early Career Fellowship. The authors have no conflict of
interest to declare.
PMID- 27609759
TI - Flying high: limits to flight performance by sparrows on the Qinghai-Tibet
Plateau.
AB - Limits to flight performance at high altitude potentially reflect variable
constraints deriving from the simultaneous challenges of hypobaric, hypodense and
cold air. Differences in flight-related morphology and maximum lifting capacity
have been well characterized for different hummingbird species across elevational
gradients, but relevant within-species variation has not yet been identified in
any bird species. Here we evaluate load-lifting capacity for Eurasian tree
sparrow (Passer montanus) populations at three different elevations in China, and
correlate maximum lifted loads with relevant anatomical features including wing
shape, wing size, and heart and lung masses. Sparrows were heavier and possessed
more rounded and longer wings at higher elevations; relative heart and lung
masses were also greater with altitude, although relative flight muscle mass
remained constant. By contrast, maximum lifting capacity relative to body weight
declined over the same elevational range, while the effective wing loading in
flight (i.e. the ratio of body weight and maximum lifted weight to total wing
area) remained constant, suggesting aerodynamic constraints on performance in
parallel with enhanced heart and lung masses to offset hypoxic challenge.
Mechanical limits to take-off performance may thus be exacerbated at higher
elevations, which may in turn result in behavioral differences in escape
responses among populations.
PMID- 27609756
TI - Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During
Early HIV Infection.
AB - BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study,
immediate combination antiretroviral therapy (cART) initiation reduced cancer
risk by 64%. We hypothesized that risk reduction was higher for infection-related
cancer and determined by differences in CD4 cell counts and human
immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident
malignancies in START were categorized into infection-related and infection
unrelated cancer. We used Cox models to assess factors associated with both
cancer categories. We used sequential adjustment for baseline covariates, cancer
risk factors, and HIV-specific variables to investigate potential mediators of
cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among
persons randomized to immediate cART (6 infection-related and 8 infection
unrelated) and 39 cancers in the deferred arm (23 infection-related and 16
infection-unrelated); hazard ratios of immediate vs deferred cART initiation were
0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95%
CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection
related cancer were older age, higher body mass index, low- to middle-income
region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell
count were independent predictors of infection-unrelated cancer. Adjustment for
latest HIV RNA level had little impact on the protective effect of immediate cART
on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4
cell count or cancer risk factors, attenuated the effect of immediate cART on
infection-unrelated cancer. CONCLUSIONS: Immediate cART initiation significantly
reduces risk of cancer. Although limited by small sample size, this benefit does
not appear to be solely attributable to HIV RNA suppression and may be also
mediated by other mechanisms.
PMID- 27609760
TI - Previous motor activity affects the transition from uncertainty to decision
making in snails.
AB - One of the most widely accepted benefits of enhanced physical activity is an
improvement in the symptoms of depression, including the facilitation of decision
making. Up until now, these effects have been shown in rodents and humans only.
Little is known about their evolutionary origin or biological basis, and the
underlying cellular mechanisms also remain relatively elusive. Here, we
demonstrate for the first time that preceding motor activity accelerates decision
making in an invertebrate, the pond snail Lymnaea stagnalis To investigate
decision making in a novel environment, snails, which normally live in water,
were placed on a flat dry surface to simulate the potentially threatening
consequence of being in an arid environment. This stimulus initiated two distinct
phases in snail behaviour: slow circular movements, followed by intense
locomotion in a chosen direction. The first phase was prolonged when the test
arena was symmetrically lit, compared with one with an apparent gradient of
light. However, forced muscular locomotion for 2 h prior to the test promoted the
transition from random circular motions to a directional crawl, accompanied by an
increase in crawling speed but with no effect on the choice of direction. Intense
locomotion for 2 h also produced a strong excitatory effect on the activity of
serotonergic neurons in L. stagnalis Our results suggest that the beneficial
effects of physical exercise on cognitive performance in mammals might have deep
roots in evolution, granting the opportunity to unravel the origins of such
effects at the single-neuron and network levels.
PMID- 27609761
TI - Behavioural integration of auditory and antennal stimulation during phonotaxis in
the field cricket Gryllus bimaculatus.
AB - Animals need to flexibly respond to stimuli from their environment without
compromising behavioural consistency. For example, female crickets orienting
toward a conspecific male's calling song in search of a mating partner need to
stay responsive to other signals that provide information about obstacles and
predators. Here, we investigate how spontaneously walking crickets and crickets
engaging in acoustically guided goal-directed navigation, i.e. phonotaxis,
respond to mechanosensory stimuli detected by their long antennae. We monitored
walking behaviour of female crickets on a trackball during lateral antennal
stimulation, which was achieved by moving a wire mesh transiently into reach of
one antenna. During antennal stimulation alone, females reduced their walking
speed, oriented toward the object and actively explored it with antennal
movements. Additionally, some crickets initially turned away from the approaching
object. Females responded in a similar way when the antennal stimulus was
presented during ongoing phonotaxis: forward velocity was reduced and phonotactic
steering was suppressed while the females turned toward and explored the object.
Further, rapid steering bouts to individual chirps, typical for female
phonotaxis, no longer occurred. Our data reveal that in this experimental
situation, antennal stimulation overrides phonotaxis for extended time periods.
Phonotaxis in natural environments, which require the integration of multiple
sensory cues, may therefore be more variable than phonotaxis measured under ideal
laboratory conditions. Combining this new behavioural paradigm with
neurophysiological methods will show where the sensory-motor integration of
antennal and acoustic stimulation occurs and how this is achieved on a
mechanistic level.
PMID- 27609762
TI - Additional in-series compliance reduces muscle force summation and alters the
time course of force relaxation during fixed-end contractions.
AB - There are high mechanical demands placed on skeletal muscles in movements
requiring rapid acceleration of the body or its limbs. Tendons are responsible
for transmitting muscle forces, but, because of their elasticity, can manipulate
the mechanics of the internal contractile apparatus. Shortening of the
contractile apparatus against the stretch of tendon affects force generation
according to known mechanical properties; however, the extent to which
differences in tendon compliance alter force development in response to a burst
of electrical impulses is unclear. To establish the influence of series
compliance on force summation, we studied electrically evoked doublet
contractions in the cane toad peroneus muscle in the presence and absence of a
compliant artificial tendon. Additional series compliance reduced tetanic force
by two-thirds, a finding predicted based on the force-length property of skeletal
muscle. Doublet force and force-time integral expressed relative to the twitch
were also reduced by additional series compliance. Active shortening over a
larger range of the ascending limb of the force-length curve and at a higher
velocity, leading to a progressive reduction in force-generating potential, could
be responsible. Muscle-tendon interaction may also explain the accelerated time
course of force relaxation in the presence of additional compliance. Our findings
suggest that a compliant tendon limits force summation under constant-length
conditions. However, high series compliance can be mechanically advantageous when
a muscle-tendon unit is actively stretched, permitting muscle fibres to generate
force almost isometrically, as shown during stretch-shorten cycles in locomotor
activities. Restricting active shortening would likely favour rapid force
development.
PMID- 27609763
TI - Object approach computation by a giant neuron and its relationship with the speed
of escape in the crab Neohelice.
AB - Upon detection of an approaching object, the crab Neohelice granulata
continuously regulates the direction and speed of escape according to ongoing
visual information. These visuomotor transformations are thought to be largely
accounted for by a small number of motion-sensitive giant neurons projecting from
the lobula (third optic neuropil) towards the supraesophageal ganglion. One of
these elements, the monostratified lobula giant neuron of type 2 (MLG2), proved
to be highly sensitive to looming stimuli (a 2D representation of an object
approach). By performing in vivo intracellular recordings, we assessed the
response of the MLG2 neuron to a variety of looming stimuli representing objects
of different sizes and velocities of approach. This allowed us to: (1) identify
some of the physiological mechanisms involved in the regulation of the MLG2
activity and test a simplified biophysical model of its response to looming
stimuli; (2) identify the stimulus optical parameters encoded by the MLG2 and
formulate a phenomenological model able to predict the temporal course of the
neural firing responses to all looming stimuli; and (3) incorporate the MLG2
encoded information of the stimulus (in terms of firing rate) into a mathematical
model able to fit the speed of the escape run of the animal. The agreement
between the model predictions and the actual escape speed measured on a treadmill
for all tested stimuli strengthens our interpretation of the computations
performed by the MLG2 and of the involvement of this neuron in the regulation of
the animal's speed of run while escaping from objects approaching with constant
speed.
PMID- 27609764
TI - The opening-closing rhythms of the subelytral cavity associated with gas exchange
patterns in diapausing Colorado potato beetle, Leptinotarsa decemlineata.
AB - The opening-closing rhythms of the subelytral cavity and associated gas exchange
patterns were monitored in diapausing Leptinotarsa decemlineata beetles.
Measurements were made by means of a flow-through CO2 analyser and a coulometric
respirometer. Under the elytra of these beetles there is a more or less tightly
enclosed space, the subelytral cavity (SEC). When the cavity was tightly closed,
air pressure inside was sub-atmospheric, as a result of oxygen uptake into the
tracheae by the beetle. In about half of the beetles, regular opening-closing
rhythms of the SEC were observed visually and also recorded; these beetles
displayed a discontinuous gas exchange pattern. The SEC opened at the start of
the CO2 burst and was immediately closed. On opening, a rapid passive suction
inflow of atmospheric air into the SEC occurred, recorded coulometrically as a
sharp upward peak. As the CO2 burst lasted beyond the closure of the SEC, we
suggest that most of the CO2 was expelled through the mesothoracic spiracles. In
the remaining beetles, the SEC was continually semi-open, and cyclic gas exchange
was exhibited. The locking mechanisms and structures between the elytra and
between the elytra and the body were examined under a stereomicroscope and by
means of microphotography. We conclude that at least some of the L. decemlineata
diapausing beetles were able to close their subelytral cavity tightly, and that
the cavity then served as a water-saving device.
PMID- 27609766
TI - A qualitative analysis of explanatory models in medically unexplained physical
symptoms presenting to a tertiary health care psychiatric facility in South
India.
AB - BACKGROUND: Knowledge about subjective perceptions and explanatory models has the
potential to inform clinical evaluation and lead to development of patient
friendly treatment models in medically unexplained physical symptoms (MUPS). AIM:
To collect qualitative data about explanatory models in MUPS. METHODS: A cross
sectional observational study was done among patients with MUPS presenting over a
2-year period to a specialty psychosomatic clinic. The Short Explanatory Model of
Illness interview was used to gather qualitative data about explanatory models
which were subsequently recoded using standard manuals. RESULTS: A total of 123
subjects were evaluated. The nature of symptoms was most commonly reported as
'non-specific' ( n = 102, 82.9%) but of moderate to severe intensity ( n = 87,
73.8%). Getting cured or showing improvement was the most common expectation from
treatment ( n = 58, 47.9%). Moderate to severe impact of symptoms was reported on
work output ( n = 100, 84%), emotional life ( n = 85, 71.4%) and physical
mobility ( n = 59, 49.1%). A considerable proportion was either dissatisfied ( n
= 61, 50%) or frankly unhappy ( n = 38, 31.4%) with treatment received.
CONCLUSION: There is a need to re-calibrate the clinical approach to people with
MUPS to enhance treatment satisfaction. Our findings could assist in evolving
culturally sensitive conceptualizations of illness and in developing patient
centred models for therapy in MUPS patients.
PMID- 27609767
TI - Deficiency of stearoyl-CoA desaturase-1 aggravates colitogenic potential of
adoptively transferred effector T cells.
AB - Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo
biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of
lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially
reduced oleate in cell membranes. An altered SCD1 level was observed during
intestinal inflammation; however, its role in modulating inflammatory bowel
disease remains elusive. Herein, we investigated the colitogenic capacity of
Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model.
Splenic effector T cells (CD4+CD25-) from age- and sex-matched wild-type (WT) and
Scd1KO mice were isolated by FACS and intraperitoneally administered to Rag1KO
mice, which were monitored for the development of colitis. At day 60 postcell
transfer, Rag1KO mice that received Scd1KO CD4+CD25- T cells displayed
accelerated and exacerbated colitis than mice receiving WT CD4+CD25- T cells.
Intriguingly, Scd1KO CD4+CD25- T cells display augmented inflammatory cytokine
profile and cellular membrane fluidity with a concomitant increase in
proinflammatory saturated fatty acids, which we postulate to potentially underlie
their augmented colitogenic potential.
PMID- 27609768
TI - Segmental differences in upregulated apical potassium channels in mammalian colon
during potassium adaptation.
AB - Rat proximal and distal colon are net K+ secretory and net K+ absorptive
epithelia, respectively. Chronic dietary K+ loading increases net K+ secretion in
the proximal colon and transforms net K+ absorption to net K+ secretion in the
distal colon, but changes in apical K+ channel expression are unclear. We
evaluated expression/activity of apical K+ (BK) channels in surface colonocytes
in proximal and distal colon of control and K+-loaded animals using patch-clamp
recording, immunohistochemistry, and Western blot analyses. In controls, BK
channels were more abundant in surface colonocytes from K+ secretory proximal
colon (39% of patches) than in those from K+-absorptive distal colon (12% of
patches). Immunostaining demonstrated more pronounced BK channel alpha-subunit
protein expression in surface cells and cells in the upper 25% of crypts in
proximal colon, compared with distal colon. Dietary K+ loading had no clear-cut
effects on the abundance, immunolocalization, or expression of BK channels in
proximal colon. By contrast, in distal colon, K+ loading 1) increased BK channel
abundance in patches from 12 to 41%; 2) increased density of immunostaining in
surface cells, which extended along the upper 50% of crypts; and 3) increased
expression of BK channel alpha-subunit protein when assessed by Western blotting
(P < 0.001). Thus apical BK channels are normally more abundant in K+ secretory
proximal colon than in K+ absorptive distal colon, and apical BK channel
expression in distal (but not proximal) colon is greatly stimulated as part of
the enhanced K+ secretory response to dietary K+ loading.
PMID- 27609769
TI - Weight loss following diet-induced obesity does not alter colon tumorigenesis in
the AOM mouse model.
AB - Obesity presents a significant public health concern given its association with
increased cancer incidence, unfavorable prognosis, and metastasis. However, there
is very little literature on the effects of weight loss, following obesity, on
risk for colon cancer or liver cancer. Therefore, we sought to study whether
intentional weight loss through diet manipulation was capable of mitigating colon
and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47%
carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity.
Subsequently, azoxymethane (AOM) was used to promote colon and liver
carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD)
containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional
weight loss. Body weight loss and excess fat reduction did not protect mice from
colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer
model even though these mice had improved blood glucose and leptin levels.
Intentional weight loss in AOM-treated mice actually produced histological
changes that resemble dysplastic alterations in the liver and presented a higher
percentage of F4/80+CD206+ macrophages and activated T cells (CD4+CD69+) in the
spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice
exposed to a HFD during the entire period of the experiment exhibited a marked
increase in proliferation and pNF-kappaB activation. Altogether, these data
suggest that intentional weight loss following chemical-induced carcinogenesis
does not affect colon tumorigenesis but may in fact negatively impact liver
repair mechanisms.
PMID- 27609770
TI - Chemical and molecular factors in irritable bowel syndrome: current knowledge,
challenges, and unanswered questions.
AB - Several chemical and molecular factors in the intestine are reported to be
altered and to have a potentially significant role in irritable bowel syndrome
(IBS), particularly in IBS with diarrhea. These include bile acids; short-chain
fatty acids; mucosal barrier proteins; mast cell products such as histamine,
proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs,
proteins, and microRNAs. This article reviews the current knowledge and
unanswered questions in the pathobiology of the chemical and molecular factors in
IBS. Evidence continues to point to significant roles in pathogenesis of these
chemical and molecular mechanisms, which may therefore constitute potential
targets for future research and therapy. However, it is still necessary to
address the interaction between these factors in the gut and to appraise how they
may influence hypervigilance in the central nervous system in patients with IBS.
PMID- 27609771
TI - Insulin promotes proliferation and fibrosing responses in activated pancreatic
stellate cells.
AB - Epidemiological studies support strong links between obesity, diabetes, and
pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC).
Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and
hyperinsulinemia, the latter due to increased insulin secretion by pancreatic
beta-cells. We reported that high-fat diet-induced PDAC progression in mice is
associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic
stellate cells (PaSC). We investigated here the effects of high concentrations of
insulin and glucose on mouse and human PaSC growth and fibrosing responses. We
found that compared with normal, pancreata from T2DM patients displayed extensive
collagen deposition and activated PaSC in islet and peri-islet exocrine pancreas.
Mice fed a high-fat diet for up to 12 mo similarly displayed increasing peri
islet fibrosis compared with mice fed control diet. Both quiescent and activated
PaSC coexpress insulin (IR; mainly A type) and IGF (IGF-1R) receptors, and both
insulin and glucose modulate receptor expression. In cultured PaSC, insulin
induced rapid tyrosine autophosphorylation of IR/IGF-1R at specific kinase domain
activation loop sites, activated Akt/mTOR/p70S6K signaling, and inactivated
FoxO1, a transcription factor that restrains cell growth. Insulin did not promote
activation of quiescent PaSC in either 5 mM or 25 mM glucose containing media.
However, in activated PaSC, insulin enhanced cell proliferation and augmented
production of extracellular matrix proteins, and these effects were abolished by
specific inhibition of mTORC1 and mTORC2. In conclusion, our data support the
concept that increased local glucose and insulin concentrations associated with
obesity and T2DM promote PaSC growth and fibrosing responses.
PMID- 27609772
TI - Role of neutral ceramidase in colon cancer.
AB - Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1
phosphate, have been linked to colon cancer, suggesting that enzymes of
sphingolipid metabolism may emerge as novel regulators and targets in colon
cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that
hydrolyzes ceramide into sphingosine, is highly expressed in the intestine;
however, its role in colon cancer has not been defined. Here we show that
molecular and pharmacological inhibition of nCDase in colon cancer cells
increases ceramide, and this is accompanied by decreased cell survival and
increased apoptosis and autophagy, with minimal effects on noncancerous cells.
Inhibition of nCDase resulted in loss of beta-catenin and inhibition of ERK,
components of pathways relevant for colon cancer development. Furthermore,
inhibition of nCDase in a xenograft model delayed tumor growth and increased
ceramide while decreasing proliferation. It is noteworthy that mice lacking
nCDase treated with azoxymethane were protected from tumor formation. Taken
together, these studies show that nCDase is pivotal for regulating initiation and
development of colon cancer, and these data suggest that this enzyme is a
suitable and novel target for colon cancer therapy.-Garcia-Barros, M., Coant, N.,
Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H.,
Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun,
Y. A. Role of neutral ceramidase in colon cancer.
PMID- 27609773
TI - Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and
enhances mammalian lung fibrosis.
AB - Pulmonary fibrosis is a progressive and often fatal condition that is believed to
be partially orchestrated by macrophages. Mechanisms that control migration of
these cells into and within the lung remain undefined. We evaluated the
contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic
calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role
of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests,
characterized its contribution to experimentally induced lung fibrosis in mice,
and defined the mechanism for our observations. Our findings reveal that relative
to control participants, patients with idiopathic pulmonary fibrosis demonstrate
excessive monocyte migration and underexpression of PLXNC1 in the lungs and
circulation, a finding that is recapitulated in the setting of scleroderma
related interstitial lung disease. Relative to wild type, PLXNC1-/- mouse
macrophages are excessively migratory, and PLXNC1-/- mice show exacerbated
collagen accumulation in response to either inhaled bleomycin or inducible lung
targeted TGF-beta1 overexpression. These findings are ameliorated by replacement
of PLXNC1 on bone marrow-derived cells or by genetic deletion of Syt7. These data
demonstrate the previously unrecognized observation that PLXNC1 deficiency
permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.
Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D.,
Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali
Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog,
E. L. Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration
and enhances mammalian lung fibrosis.
PMID- 27609774
TI - Identification of the epidermal growth factor receptor as the receptor for
Salmonella Rck-dependent invasion.
AB - The Salmonella Rck outer membrane protein binds to the cell surface, which leads
to bacterial internalization via a Zipper mechanism. This invasion process
requires induction of cellular signals, including phosphorylation of tyrosine
proteins, and activation of c-Src and PI3K, which arises as a result of an
interaction with a host cell surface receptor. In this study, epidermal growth
factor receptor (EGFR) was identified as the cell signaling receptor required for
Rck-mediated adhesion and internalization. First, Rck-mediated adhesion and
internalization were shown to be altered when EGFR expression and activity were
modulated. Then, immunoprecipitations were performed to demonstrate the Rck-EGFR
interaction. Furthermore, surface plasmon resonance biosensor and homogeneous
time-resolved fluorescence technologies were used to demonstrate the direct
interaction of Rck with the extracellular domain of human EGFR. Finally, our
study strongly suggests a noncompetitive binding of Rck and EGF to EGFR. Overall,
these results demonstrate that Rck is able to bind to EGFR and thereby establish
a tight adherence to provide a signaling cascade, which leads to internalization
of Rck-expressing bacteria.-Wiedemann, A., Mijouin, L., Ayoub, M. A., Barilleau,
E., Canepa, S., Teixeira-Gomes, A. P., Le Vern, Y., Rosselin, M., Reiter, E.,
Velge, P. Identification of the epidermal growth factor receptor as the receptor
for Salmonella Rck-dependent invasion.
PMID- 27609776
TI - Prevalence and sociodemographic correlates of metabolic syndrome in school-aged
children and their parents in nine Mesoamerican countries.
AB - OBJECTIVE: To ascertain the prevalence and sociodemographic correlates of
cardiometabolic risk factors in adults and school-aged children from Mesoamerica.
DESIGN: Cross-sectional study with convenience sampling. In adults, metabolic
syndrome was defined according to the National Cholesterol Education Program's
Adult Treatment Panel III (ATP III) criteria. In children, we calculated a
continuous sex- and age-standardized metabolic risk score using variables
corresponding to adult ATP III criteria. Metabolic syndrome prevalence in adults
and risk score distribution in children were compared across levels of
sociodemographic characteristics with use of Poisson and linear regression,
respectively. SETTING: Capital cities of Guatemala, El Salvador, the Dominican
Republic, Honduras, Nicaragua, Panama, Costa Rica, the Mexican State of Chiapas
(Tuxtla Gutierrez city) and Belize. SUBJECTS: Families (n 267), comprising one
child aged 7-12 years and their biological parents. RESULTS: The prevalence of
metabolic syndrome was 37.9 % among women and 35.3 % among men. The most common
component was low HDL cholesterol, 83.3 % in women and 78.9 % in men. Prevalence
was positively associated with age. In women, metabolic syndrome was inversely
related to education level whereas in men it was positively associated with
household food security and height, after adjustment. The metabolic risk score in
children was inversely related to parental height, and positively associated with
height-for-age and with having parents with the metabolic syndrome. CONCLUSIONS:
Metabolic syndrome is highly prevalent in Mesoamerica. The burden of metabolic
risk factors disproportionately affects women and children of lower socio
economic status and men of higher socio-economic status.
PMID- 27609775
TI - Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the
cavernous nerve to promote regeneration and prevent erectile dysfunction.
AB - Erectile dysfunction (ED) has high impact on quality of life in prostatectomy,
diabetic and aging patients. An underlying mechanism is cavernous nerve (CN)
injury, which causes ED in up to 80% of prostatectomy patients. We examine how
sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber
hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors
patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO
undergoes anterograde transport to signal to downstream targets. With crush
injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO
localization changes to the neuronal cell surface, and anterograde transport
stops. With SHH treatment SHH is taken up at the injury site and undergoes
retrograde transport to PG neurons, allowing SMO transport to occur, and neurons
remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal,
glial and downstream target signaling, and is significant as a regenerative
therapy.
PMID- 27609777
TI - Molecular mechanisms of LL-37-induced receptor activation: An overview.
AB - The human cathelicidin peptide LL-37 plays a crucial role in the immune system on
many levels, from the first line of defense in epithelial cells to restoring the
tissue after infection. On host cells, the majority of the LL-37-induced effects
are mediated via the direct or indirect activation of several structurally
unrelated cell surface receptors or intracellular targets. How LL-37 is able to
affect multiple receptors is currently not well understood. So far, the
mechanistic details underlying receptor activation are poorly investigated and
evidence for a conventional ligand/receptor interaction is scarce. Over the past
few decades, a large number of studies have reported on the activation of a
receptor and/or components of the downstream signal transduction pathway induced
by LL-37. This review summarizes the current knowledge on molecular mechanisms
underlying LL-37-induced receptor activation.
PMID- 27609778
TI - Early adverse events of per-oral endoscopic myotomy.
AB - BACKGROUND AND AIMS: The recently developed technique of per-oral endoscopic
myotomy (POEM) has been shown to be effective for the therapy of esophageal
motility disorders. Limited information is available about POEM adverse events
(AEs). METHODS: POEM was performed on 241 patients (58% male; mean age, 47.4 +/-
16.4 years) under general anesthesia over 61 months. The main outcome was the
rate of intra- and post-procedural AEs. Post-procedural checks comprised clinical
and laboratory examinations and endoscopy, with further follow-ups performed at
3, 6, and 12 months. RESULTS: Of the 241 procedures, 238 were successfully
completed (mean procedure time, 100.2 +/- 39.5 min). Reasons for abortion were
excessive submucosal fibrosis preventing submucosal tunneling. Three patients had
severe procedural-related AEs (SAE rate, 1.2%); 1 case of pneumothorax required
intra-procedural drainage, and 2 patients had delayed SAEs (1 ischemic gastric
cardia perforation and 1 hemothorax, both leading to surgery). The overall rate
of minor AEs was 31.1%, mainly prolonged intra-procedural bleeding (>15 min
hemostasis) and defects of the mucosa overlying the tunnel; none led to
clinically relevant signs or symptoms. Patients experiencing any AE had a
significantly prolonged hospital stay (P = .037) and a trend toward prolonged
procedure time (P = .094). Neck/upper thoracic emphysema and free abdominal air
were noted in 31.5% and 35.7%, respectively (95.3% drained), but without relevant
sequelae. CONCLUSIONS: POEM has a low rate of SAEs; minor AEs are more frequent
but lack a consistent definition. Therefore, based on our experience and
literature analysis, we suggest a classification of AEs for POEM. (Clinical
trials registration number: NCT01405417.).
PMID- 27609779
TI - Use of electronic cigarettes in smoke-free environments.
AB - BACKGROUND: Although most US states prohibit cigarette smoking in public places
and worksites, fewer jurisdictions regulate indoor use of electronic cigarettes
(e-cigarettes). Given the dramatic increase in e-cigarette use and concern about
its impact on non-users, there is a need to examine the use of e-cigarettes in
smoke-free environments and related attitudes and perceptions. METHODS: Recruited
from a nationally representative adult panel (GfK's KnowledgePanel), 952 current
users of e-cigarettes completed a cross-sectional online survey in 2014.
Multivariate logistic regressions were conducted to examine the factors
associated with ever using e-cigarettes in smoke-free environments. RESULTS:
Overall, 59.5% of e-cigarette users had vaped where cigarette smoking was not
allowed. Young adults (18-29 years) were most likely to do so, 74.2%. The places
of first-time use most often mentioned were service venues (bar, restaurant,
lounge and club), 30.7%, followed by worksites, 23.5%. Daily e-cigarette users
were more likely to have vaped in smoke-free environments than non-daily users
(OR=2.08, p=0.012). Only 2.5% of those who used e-cigarettes in smoke-free
environments reported negative reactions from other people. Most e-cigarette
users did not think e-cigarettes are harmful to themselves or to by-standers, and
thus should not be banned where smoking is; those who had used e-cigarettes where
smoking is banned were even more likely to hold these views. CONCLUSIONS: E
cigarette use in smoke-free environments was common, suggesting that most e
cigarette users do not consider smoke-free laws to apply to e-cigarettes.
Explicit laws should be considered if jurisdictions want to prohibit e-cigarette
use in public places.
PMID- 27609780
TI - Inequities in tobacco retailer sales to minors by neighbourhood racial/ethnic
composition, poverty and segregation, USA, 2015.
AB - OBJECTIVE: Tobacco retailers are an important source of tobacco products for
minors. Previous research shows racial discrimination in sales to minors, but no
national study has examined neighbourhood correlates of retailer under-age sales.
METHODS: We accessed publicly available results of 2015 US Food and Drug
Administration (FDA) inspections of tobacco retailers (n=108 614). In this cross
sectional study, we used multilevel logistic regression to predict the likelihood
of retailer sale to a minor based on tract characteristics. We assessed the
proportion of residents identifying as American Indian, Asian, Black, Latino and
White; Isolation Index scores for each racial/ethnic group; the proportion of
people less than age 65 living in poverty; and the proportion of residents age 10
17 in relation to retailer inspection results. RESULTS: The proportion of
American Indian residents, Black residents, Latino residents and residents less
than age 65 under the poverty line in a neighbourhood are independently,
positively associated with the likelihood that a retailer in that neighbourhood
will fail an under-age buy inspection. The proportion of White residents and
residents age 10-17 are independently, negatively associated with the likelihood
of sale of tobacco products to a minor. Isolation Index scores show a similar
pattern. In multivariable models holding neighbourhood characteristics constant,
higher proportions of Black (+), Latino (+) and age 10-17 (-) residents remained
significant predictors of the likelihood of under-age sale. DISCUSSION:
Regulatory agencies should consider oversampling retailers in areas with higher
likelihood of sales to minors for inspection. Interventions with tobacco
retailers to reduce inequities in youth access should be implemented.
PMID- 27609781
TI - Use of imagery and text that could convey reduced harm in American Spirit
advertisements.
AB - BACKGROUND: In 2015, the US Food and Drug Administration issued warning letters
to three tobacco companies regarding use of the terms 'natural' and/or 'additive
free' to describe their products, as these terms inaccurately convey reduced
harm. Yet, tobacco companies engage in a variety of alternate techniques to
attempt to convey the same 'natural' (and thus reduced harm) message. It is
critical to monitor these practices to inform regulatory action. OBJECTIVE: To
describe the marketing techniques used in Natural American Spirit (American
Spirit) ads that could convey a natural and less harmful product image. METHODS:
Trained coders content analysed 142 American Spirit ads from 2012 to 2016.
RESULTS: In addition to use of the terms 'natural' and 'additive-free', American
Spirit ads engage in a variety of other linguistic and iconic techniques that
could convey reduced harm, such as references to small, local or organic farming,
eco-friendly practices, and plant, farming and other nature-related imagery.
CONCLUSIONS: American Spirit ads use a wide range of marketing techniques to
convey a natural product image, which could subsequently communicate reduced
harm.
PMID- 27609783
TI - An RCT of an Online Parenting Program for Parents of Preschool-Aged Children With
ADHD Symptoms.
AB - OBJECTIVE: This randomized control trial evaluated the efficacy of an online self
help program in a sample of parents of preschoolers with ADHD symptoms. METHOD:
Parents were randomly assigned to the intervention group (n = 27) or the delayed
intervention group (n = 26). Child behavior measures were completed by mothers,
fathers, and teachers, and parenting measures were completed by mothers. RESULTS:
Intent-to-treat analyses indicated significant post-intervention improvements in
mother-rated child hyperactivity/inattention, restlessness/impulsivity,
defiance/aggression, social functioning, and teacher-rated prosocial behavior, as
well as significant improvements in maternal over-reactivity, verbosity, laxness,
positive parenting, parenting satisfaction, self-efficacy, stress, and
depression. At 6-month follow-up, effects were maintained for maternal over
reactivity and verbosity, parenting satisfaction and self-efficacy, and parental
stress and depression. CONCLUSION: This study provides evidence for the
effectiveness of an online self-help parenting program in reducing preschool
inattentive behavior difficulties, and in increasing parenting competence,
satisfaction in the parenting role, and maternal well-being.
PMID- 27609782
TI - Potential impact of pre-exposure prophylaxis for female sex workers and men who
have sex with men in Bangalore, India: a mathematical modelling study.
AB - INTRODUCTION: In Bangalore, new HIV infections of female sex workers and men who
have sex with men continue to occur, despite high condom use. Pre-exposure
prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP
demonstration projects are underway amongst Indian female sex workers. We
estimated the impact and efficiency of prioritizing PrEP to female sex workers
and/or men who have sex with men in Bangalore. METHODS: A mathematical model of
HIV transmission and treatment for female sex workers, clients, men who have sex
with men and low-risk groups was parameterized and fitted to Bangalore data. The
proportion of transmission attributable (population attributable fraction) to
commercial sex and sex between men was calculated. PrEP impact (infections
averted, life-years gained) and efficiency (life-years gained/infections averted
per 100 person-years on PrEP) were estimated for different levels of PrEP
adherence, coverage and prioritization strategies (female sex workers, high-risk
men who have sex with men, both female sex workers and high-risk men who have sex
with men, or female sex workers with lower condom use), under current conditions
and in a scenario with lower baseline condom use amongst key populations.
RESULTS: Population attributable fractions for commercial sex and sex between men
have declined over time, and they are predicted to account for 19% of all new
infections between 2016 and 2025. PrEP could prevent a substantial proportion of
infections amongst female sex workers and men who have sex with men in this
setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which
could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore
population. Impact and efficiency in the whole population was greater if female
sex workers were prioritized. Efficiency increased, but impact decreased, if only
female sex workers with lower condom use were given PrEP. Greater impact and
efficiency was predicted for the scenario with lower condom use. CONCLUSIONS:
PrEP could be beneficial for female sex workers and men who have sex with men in
Bangalore, and give some benefits in the general population, especially in
similar settings with lower condom use levels.
PMID- 27609784
TI - Health department's NHS accounts are "rotten," say MPs.
PMID- 27609786
TI - Erythropoietin Pretreatment of Transplanted Endothelial Colony-Forming Cells
Enhances Recovery in a Cerebral Ischemia Model by Increasing Their Homing
Ability: A SPECT/CT Study.
AB - : Endothelial colony-forming cells (ECFCs) are promising candidates for cell
therapy of ischemic diseases, as less than 10% of patients with an ischemic
stroke are eligible for thrombolysis. We previously reported that erythropoietin
priming of ECFCs increased their in vitro and in vivo angiogenic properties in
mice with hindlimb ischemia. The present study used SPECT/CT to evaluate whether
priming of ECFCs with erythropoietin could enhance their homing to the ischemic
site after transient middle cerebral artery occlusion (MCAO) followed by
reperfusion in rats and potentiate their protective or regenerative effect on
blood-brain barrier (BBB) disruption, cerebral apoptosis, and cerebral blood flow
(CBF). METHODS: Rats underwent a 1-h MCAO followed by reperfusion and then 1 d
after MCAO received an intravenous injection of either PBS (control, n = 10), PBS
primed ECFCs (ECFCPBS, n = 13), or erythropoietin-primed ECFCs (ECFCEPO, n = 10).
ECFC homing and the effect on BBB disruption, cerebral apoptosis, and CBF were
evaluated by SPECT/CT up to 14 d after MCAO. The results were expressed as median
+/- interquartile range for ipsilateral-to-contralateral ratio of the activity in
middle cerebral artery-vascularized territories in each hemisphere. Histologic
evaluation of neuronal survival and astrocytic proliferation was performed on day
14. RESULTS: Erythropoietin priming increased homing of ECFCs to the ischemic
hemisphere (ECFCPBS, 111.0% +/- 16.0%; ECFCEPO, 146.5% +/- 13.3%). BBB disruption
was significantly reduced (control, 387% +/- 153%; ECFCPBS, 151% +/- 46% [P <
0.05]; ECFCEPO, 112% +/- 9% [P < 0.001]) and correlated negatively with ECFC
homing (Pearson r = -0.6930, P = 0.0002). Cerebral apoptosis was significantly
reduced (control, 161% +/- 10%; ECFCPBS, 141% +/- 9% [P < 0.05]; ECFCEPO,118% +/-
5% [P < 0.001]) and correlated negatively with ECFC homing (r = -0.7251, P <
0.0001). CBF was significantly restored with ECFCs and almost totally so with
erythropoietin priming (control, 72% +/- 2%; ECFCPBS, 90% +/- 4% [P < 0.01];
ECFCEPO, 99% +/- 4% [P < 0.001]) and correlated positively with ECFC homing (r =
0.7348, P < 0.0001). Immunoblocking against the CD146 receptor on ECFCs
highlighted its notable role in ECFC homing with erythropoietin priming (ECFCEPO,
147% +/- 14%, n = 4; ECFCEPO with antibody against CD146, 101% +/- 12%, n = 4 [P
< 0.05]). CONCLUSION: Priming with erythropoietin before cell transplantation is
an efficient strategy to amplify the migratory and engraftment capacities of
ECFCs and their beneficial impact on BBB disruption, apoptosis, and CBF.
PMID- 27609785
TI - Vitrectomy with and without encircling band for pseudophakic retinal detachment:
VIPER Study Report No 2-main results.
AB - BACKGROUND: It is unclear whether or not an additional encircling band improves
outcome in vitrectomy for pseudophakic retinal detachment (PRD). Also unclear is
whether small gauge transconjunctival trocar-guided vitrectomy is as successful
as conventional 20 gauge (G) vitrectomy. METHODS: 257 adult patients with
uncomplicated PRD were enrolled in 14 vitreoretinal centres across Germany.
Contingent on availability of qualified surgeons, eligible patients were randomly
assigned either (i) with ratio 1:1 to 20 G vitrectomy plus encircling band (group
E1) or 20 G vitrectomy without any buckle (group C) or (ii) with ratios 1:1:1 to
group E1, C or 23/25 G vitrectomy without any buckle (group E2). Treatment
success was defined as no indication for any retina reattaching procedure during
the follow-up of 6 months. RESULTS: Success was reached in 79.0% (=79/100, group
E1) versus 73.5% (=72/98, group C) (p=0.558, OR 1.32, 95% CI 0.65 to 2.65. In
group E2 87.7% (=50/57) of patients reached success compared with 78.7% (=48/61)
in group C, demonstrating non-inferiority of E2 to C regarding the prespecified
margin of 0.8 (OR scale; p=0.05, OR 2.17, 95% CI 0.80 to 5.89). Best corrected
visual acuity significantly increased after surgery independent of technique,
that is, on average -0.7 (from 1.0 to 0.3) logMAR. Patients suffered from a shift
in spherical refraction of -1.0 D in group E1 compared with -0.1 D in group C.
Similarly, intraoperative complications (15.2% vs 8.8% of patients) and serious
adverse events (30.3% vs 22.5% of patients) were more frequent in group E1.
CONCLUSIONS: Vitrectomy with gas is an efficient and safe treatment for
uncomplicated PRD. An additional encircling band does not significantly reduce
the risk for any second procedure necessary to reattach the retina in 20 G
vitrectomy. Small gauge transconjunctival vitrectomy is not inferior to the
conventional 20 G technique. TRIAL REGISTRATION NUMBER: DKRS 00003158, Results.
PMID- 27609787
TI - Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small
Animal PET Imaging.
AB - : Patient premedication with carbidopa seems to improve the accuracy of 6-18F
fluoro-3,4-dihydroxy-l-phenylalanine (18F-FDOPA) PET for insulinoma diagnosis.
However, the risk of PET false-negative results in the presence of carbidopa is a
concern. Consequently, we aimed to evaluate the effect of carbidopa on 18F-FDOPA
uptake in insulinoma beta-cells and an insulinoma xenograft model in mice.
METHODS: 18F-FDOPA in vitro accumulation was assessed in the murine beta-cell
line RIN-m5F. In vivo small-animal PET experiments were performed on tumor
bearing nude mice after subcutaneous injection of RIN-m5F cells. Experiments were
conducted with and without carbidopa pretreatment. RESULTS: Incubation of RIN-m5F
cells with 80 MUM carbidopa did not significantly affect the cellular
accumulation of 18F-FDOPA. Tumor xenografts were clearly detectable by small
animal PET in all cases. Insulinoma xenografts in carbidopa-treated mice showed
significantly higher 18F-FDOPA uptake than those in nontreated mice. Regardless
of carbidopa premedication, the xenografts were characterized by an early
increase in 18F-FDOPA uptake and then a progressive reduction over time.
CONCLUSION: Carbidopa did not influence in vitro 18F-FDOPA accumulation in RIN
m5F cells but improved insulinoma imaging in vivo. Our findings increase current
knowledge about the 18F-FDOPA uptake profile of RIN-m5F cells and a related
xenograft model. To our knowledge, the present work represents the first
preclinical research specifically focused on insulinomas, with potential
translational implications.
PMID- 27609788
TI - Safety, Dosimetry, and Tumor Detection Ability of 68Ga-NOTA-AE105: First-in-Human
Study of a Novel Radioligand for uPAR PET Imaging.
AB - The overexpression of urokinase-type plasminogen activator receptors (uPARs)
represents an established biomarker for aggressiveness in most common malignant
diseases, including breast cancer (BC), prostate cancer (PC), and urinary bladder
cancer (UBC), and is therefore an important target for new cancer therapeutic and
diagnostic strategies. In this study, uPAR PET imaging using a 68Ga-labeled
version of the uPAR-targeting peptide (AE105) was investigated in a group of
patients with BC, PC, and UBC. The aim of this first-in-human, phase I clinical
trial was to investigate the safety and biodistribution in normal tissues and
uptake in tumor lesions. Methods: Ten patients (6 PC, 2 BC, and 2 UBC) received a
single intravenous dose of 68Ga-NOTA-AE105 (154 +/- 59 MBq; range, 48-208 MBq).
The biodistribution and radiation dosimetry were assessed by serial whole-body
PET/CT scans (10 min, 1 h, and 2 h after injection). Safety assessment included
measurements of vital signs with regular intervals during the imaging sessions
and laboratory blood screening tests performed before and after injection. In a
subgroup of patients, the in vivo stability of 68Ga-NOTA-AE105 was determined in
collected blood and urine. PET images were visually analyzed for visible tumor
uptake of 68Ga-NOTA-AE105, and SUVs were obtained from tumor lesions by manually
drawing volumes of interest in the malignant tissue. Results: No adverse events
or clinically detectable pharmacologic effects were found. The radioligand
exhibited good in vivo stability and fast clearance from tissue compartments
primarily by renal excretion. The effective dose was 0.015 mSv/MBq, leading to a
radiation burden of 3 mSv when the clinical target dose of 200 MBq was used. In
addition, radioligand accumulation was seen in primary tumor lesions as well as
in metastases. Conclusion: This first-in-human, phase I clinical trial
demonstrates the safe use and clinical potential of 68Ga-NOTA-AE105 as a new
radioligand for uPAR PET imaging in cancer patients.
PMID- 27609789
TI - 68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in
Oncology.
AB - : Because overexpression of the gastrin-releasing peptide receptor (GRPR) has
been reported on various cancer types, for example, prostate cancer and breast
cancer, targeting this receptor with radioligands might have a significant impact
on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA
coupled GRPR antagonist with high affinity for GRPR and excellent in vivo
stability. The purpose of this preclinical study was to further explore the use
of NeoBOMB1 for theranostic application by determining the biodistribution of
68Ga-NeoBOMB1 and 177Lu-NeoBOMB1. METHODS: PC-3 tumor-xenografted BALB/c nu/nu
mice were injected with either approximately 13 MBq/250 pmol 68Ga-NeoBOMB1 or a
low (~1 MBq/200 pmol) versus high (~1 MBq/10 pmol) peptide amount of 177Lu
NeoBOMB1, after which biodistribution and imaging studies were performed. At 6
time points (15, 30, 60, 120, 240, and 360 min for 68Ga-NeoBOMB1 and 1, 4, 24,
48, 96, and 168 h for 177Lu-NeoBOMB1) postinjection tumor and organ uptake was
determined. To assess receptor specificity, additional groups of animals were
coinjected with an excess of unlabeled NeoBOMB1. Results of the biodistribution
studies were used to determine pharmacokinetics and dosimetry. Furthermore,
PET/CT and SPECT/MRI were performed. RESULTS: Injection of approximately 250 pmol
68Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4 +/- 2.3 and 22.7 +/
3.3 percentage injected dose per gram (%ID/g) of tissue, respectively, at 120
min after injection. 177Lu-NeoBOMB1 biodistribution studies revealed a higher
tumor uptake (17.9 +/- 3.3 vs. 11.6 +/- 1.3 %ID/g of tissue at 240 min after
injection) and a lower pancreatic uptake (19.8 +/- 6.9 vs. 105 +/- 13 %ID/g of
tissue at 240 min after injection) with the higher peptide amount injected,
leading to a significant increase in the absorbed dose to the tumor versus the
pancreas (200 pmol, 570 vs. 265 mGy/MBq; 10 pmol, 435 vs. 1393 mGy/MBq). Using
these data to predict patient dosimetry, we found a kidney, pancreas, and liver
exposure of 0.10, 0.65, and 0.06 mGy/MBq, respectively. Imaging studies resulted
in good visualization of the tumor with both 68Ga-NeoBOMB1 and 177Lu-NeoBOMB1.
CONCLUSION: Our findings indicate that 68Ga- or 177Lu-labeled NeoBOMB1 is a
promising radiotracer with excellent tumor uptake and favorable pharmacokinetics
for imaging and therapy of GRPR-expressing tumors.
PMID- 27609791
TI - Comparison of 11C-Methionine and 18F-FDG PET/CT for Staging and Follow-up of
Pediatric Lymphoma.
AB - Methionine transport across plasma membranes occurs via the large amino acid
transporter, which is overexpressed in malignant cells, leading to tracer
accumulation within tumors. We investigated the uptake of 11C-methionine (11C
MET) in children and young adults with Hodgkin lymphoma (HL) or non-Hodgkin
lymphoma (NHL) and compared the biodistribution of 11C-MET PET/CT with that of
18F-FDG PET/CT. Methods: Conducted under an investigational new drug
authorization, we prospectively enrolled patients with newly diagnosed HL (n =
19) and NHL (n = 2) onto the Institutional Review Board-approved investigation of
11C-MET PET/CT. After a minimum 4-h fast, patients received 740 MBq/1.7 m2
(maximum, 740 MBq [20 mCi/1.7 m2; maximum, 20 mCi]) of 11C-methionine
intravenously. PET/CT was performed 5 min after injection from the vertex to
thighs at 3 min per bed position. In a separate session, patients received 5.5
MBq/kg (maximum, 485 MBq [0.15 mCi/kg; maximum, 12 mCi]) of 18F-FDG with imaging
initiated approximately 1 h after radiopharmaceutical administration. All studies
were reviewed by consensus of 2 senior imaging specialists. The presence of
metabolic activity on baseline studies was compared among 17 nodal groups.
Results: Eighteen patients (11 male; median age, 15.2 y; age range, 9.5-22.6 y)
comprised the study cohort. All had paired 11C-MET PET/CT and 18F-FDG PET/CT
studies at diagnosis. At baseline, 3 nodal groups demonstrating discordant
metabolic activity by both 18F-FDG PET/CT and 11C-MET PET/CT were Waldeyer's
ring, paraaortic region, and the liver. All others were found to have concordant
metabolic activity. Normal intense 11C-MET uptake in the pancreas and liver
reduced sensitivity for disease detection in these regions. At follow-up, 14 of
15 study pairs had concordant results. Conclusion:11C-MET uptake is elevated in
most regions involved with lymphoma at diagnosis and follow-up. Its utility in
the abdomen is limited by uptake in normal structures.
PMID- 27609790
TI - Feasibility of Multiparametric Imaging with PET/MR in Head and Neck Squamous Cell
Carcinoma.
AB - : The purpose of this study was to investigate and assess the correlation and
reproducibility of multiparametric imaging in head and neck cancer patients.
METHODS: Twenty-one patients were included in this prospective scan-rescan study.
All patients were scanned twice on an integrated PET and MRI scanner. Gross tumor
volumes were defined on T2-weighted MR images, and volumes of interest were
defined on diffusion-weighted MRI and 18F-FDG PET (VOIDWI, VOIPET). Overlap
between volumes was assessed as a percentwise overlap. 18F-FDG uptake and
diffusion were measured using SUV and apparent diffusion coefficient, and
correlation was tested across and within patients and as a voxel-by-voxel
analysis. RESULTS: Seventeen patients were available for correlation analysis,
and 12 patients were available for assessment of tumor overlap. The median tumor
overlap between VOIDWI and VOIPET was 82% (VOIDWI in VOIPET) and 62% (VOIPET in
VOIDWI) on scan 1 and scan 2, respectively. Across patients, the correlation
between SUV and apparent diffusion coefficient was weak and nonsignificant.
However, in individual patients a weak but significant correlation was identified
on a voxel-by-voxel basis. CONCLUSION: In multiparametric imaging with the
integrated PET/MR scanner, the VOIs from DWI and 18F-FDG PET were both within the
target volume for radiotherapy and overlapped substantially although not
completely. No correlation between 18F-FDG uptake and DWI could be found across
patients, but within individual patients a statistically significant, but weak,
voxel-by-voxel correlation was found. The findings suggest that information on
glucose uptake and diffusion coefficient carries complementary information of
interest that may be relevant for radiotherapy treatment planning.
PMID- 27609794
TI - Junior doctors' dispute: where are we now?
PMID- 27609795
TI - European Medicines Agency: leave the UK but remain the same.
PMID- 27609793
TI - Integrating care for neurodevelopmental disorders by unpacking control: A
grounded theory study.
AB - BACKGROUND: To establish integrated healthcare pathways for patients with
neurodevelopmental disorders (ND) such as autism spectrum disorder and attention
deficit hyperactivity disorder is challenging. This study sets out to investigate
the main concerns for healthcare professionals when integrating ND care pathways
and how they resolve these concerns. METHODS: Using classic grounded theory
(Glaser), we analysed efforts to improve and integrate an ND care pathway for
children and youth in a Swedish region over a period of 6 years. Data from 42
individual interviews with a range of ND professionals, nine group interviews
with healthcare teams, participant observation, a 2-day dialogue conference,
focus group meetings, regional media coverage, and reports from other Swedish
regional ND projects were analysed. RESULTS: The main concern for participants
was to deal with overwhelming ND complexity by unpacking control, which is
control over strategies to define patients' status and needs. Unpacking control
is key to the professionals' strivings to expand constructive life space for
patients, to squeeze health care to reach available care goals, to promote
professional ideologies, and to uphold workplace integrity. Control-seeking
behaviour in relation to ND unpacking is ubiquitous and complicates integration
of ND care pathways. CONCLUSIONS: The Unpacking control theory expands central
aspects of professions theory and may help to improve ND care development.
PMID- 27609792
TI - Impact of 18F-Fluciclovine PET on Target Volume Definition for Postprostatectomy
Salvage Radiotherapy: Initial Findings from a Randomized Trial.
AB - The purpose of this study was to evaluate the role of the synthetic amino acid
PET radiotracer 18F-fluciclovine in modifying the defined clinical and treatment
planning target volumes in postprostatectomy patients undergoing salvage
radiotherapy and to evaluate the resulting dosimetric consequences to surrounding
organs at risk. Methods: Ninety-six patients were enrolled in a randomized,
prospective intention-to-treat clinical trial for potential salvage radiotherapy
for recurrent prostate cancer after prostatectomy. The initial treatment plan was
based on the results from conventional abdominopelvic CT and MRI. The 45 patients
in the experimental arm also underwent abdominopelvic 18F-fluciclovine PET/CT,
and the images were registered with the conventional images to determine whether
the results would modify the initial treatment plan. The 51 patients in the
control arm did not undergo 18F-fluciclovine PET/CT. For each patient, the
clinical and treatment-planning target volumes that would have been treated
before 18F-fluciclovine registration were compared with those after registration.
For organs at risk (rectum, bladder, and penile bulb), the volumes receiving 40
Gy and 65 Gy before registration were compared with those after registration.
Statistical comparisons were made using the paired t test. Acute genitourinary
and gastrointestinal toxicity as defined by the Radiation Therapy Oncology Group
was compared between the control and experimental arms using the chi2 test.
Results: In 24 cases, radiotherapy was planned to a clinical target volume
consisting of the prostate bed alone (CTV) (64.8-66.6 Gy). In 21 cases,
radiotherapy was planned to a clinical target volume consisting of the pelvis
(CTV1) (45.0 Gy) followed by a boost to the prostate bed (CTV2) (19.8-25.2 Gy).
In each case, the respective treatment-planning target volume expansion (PTV,
PTV1, or PTV2) was 0.8 cm (0.6 cm posterior). With the exception of PTV2, all
postregistration volumes were significantly larger than the corresponding
preregistration volumes. Analysis of the rectum, bladder, and penile bulb volumes
receiving 40 Gy and 60 Gy demonstrated that only the penile bulb volumes were
significantly higher after registration. No significant differences in acute
genitourinary or gastrointestinal toxicity were observed. Conclusion: Including
information from 18F-fluciclovine PET in the treatment-planning process led to
significant differences in the defined target volume, with higher doses to the
penile bulb but no significant differences in rectal or bladder dose or in acute
genitourinary or gastrointestinal toxicity. Longer follow-up is needed to
determine the impact of 18F-fluciclovine PET on cancer control and late toxicity
endpoints.
PMID- 27609796
TI - More thoughts on intubation trauma.
PMID- 27609797
TI - Whistle-blowing and duty of candour in the National Health Service: a 'history
and policy' case study of the 1960s and 2010s.
PMID- 27609798
TI - Food: a new form of personalised (gut microbiome) medicine for chronic diseases?
AB - Filling in the knowledge gaps between what we eat and the diseases we develop may
lie in our guts, literally. The human large intestine houses the largest
reservoir of microorganisms in or on the human body. With a 100-fold greater gene
count than humans, the gut microbiome has huge potential to place a large
metabolic burden (or advantage) on its host. The number of diverse gut microbial
species is diminished in nearly all modern chronic conditions studied. The
'Western diet', rich in animal protein, fats and artificial additives, and
lacking in fibre, beneficial microbes, plant phytochemicals, vitamins and
minerals, is thought to drive these conditions by encouraging gut dysbiosis.
Evidence from recent dietary intervention studies suggest adopting a plant-based,
minimally processed high-fibre diet may rapidly reverse the effects of meat-based
diets on the gut microbiome. However, recent work has shown that individual diet
responses may be complicated by host genetics and the wide variation in the gut
microbiome. Now that we measure genes and microbes more accurately, we are
embarking on an exciting era of using both food and microbes as potential
therapies.
PMID- 27609800
TI - Petrarch's letter to Boccaccio 'on the proud and presumptuous behaviour of
physicians'.
PMID- 27609799
TI - Change in plasma volume and prognosis in acute decompensated heart failure: an
observational cohort study.
AB - OBJECTIVES: This study aimed to develop an inexpensive, readily available
prognostic indicator in acute decompensated heart failure patients to guide
management and improve outcome. Prognostic biomarkers for heart failure exist but
are expensive and not routinely performed. Increasing plasma volume has been
associated with worse outcomes. SETTING: UK University Teaching Hospital. DESIGN:
Observational Cohort study. PARTICIPANTS: 967 patients with acute decompensated
heart failure. METHODS: Haemoglobin and haematocrit were measured at admission
and discharge and were used to calculate the plasma volume change using the
Strauss-Davis-Rosenbaum formula. MAIN OUTCOME MEASURES: Endpoints were death and
the composite of death and/or heart failure hospitalisation. Change in plasma
volume was added to ADHERE scoring to determine predictive value. RESULTS: During
follow-up, 536 died and 626 died or were hospitalised with heart failure.
Multivariable Cox models showed change in plasma volume was an independent
predictor of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.150
[1.031-1.283], p = 0.012) and death or heart failure hospitalisation (HR: 1.138
[1.029-1.259], p = 0.012). Kaplan-Meier analysis of change in plasma volume
tertiles for outcome measures showed significant difference for the top tertile
compared to the lower two. Multivariable analysis of change in plasma volume with
ADHERE scoring showed change in plasma volume change remained an independent
predictor of death (HR: 1.138 [1.026-1.261], p = 0.015) and death or heart
failure hospitalisation (HR: 1.129 [1.025-1.243], p = 0.014). CONCLUSIONS: Change
in plasma volume over an admission can be used for prognostication and adds value
to the ADHERE score. Change in plasma volume can be easily and inexpensively
calculated from routine blood tests. Clinically, this may facilitate targeted
treatment of acute decompensated heart failure patients at greatest risk.
PMID- 27609804
TI - Temperate tree species show identical response in tree water deficit but
different sensitivities in sap flow to summer soil drying.
AB - Temperate forests are expected to be particularly vulnerable to drought and soil
drying because they are not adapted to such conditions and perform best in mesic
environments. Here we ask (i) how sensitively four common temperate tree species
(Fagus sylvatica, Picea abies, Acer pseudoplatanus and Fraxinus excelsior)
respond in their water relations to summer soil drying and seek to determine (ii)
if species-specific responses to summer soil drying are related to the onset of
declining water status across the four species. Throughout 2012 and 2013 we
determined tree water deficit (TWD) as a proxy for tree water status from
recorded stem radius changes and monitored sap flow rates with sensors on 16
mature trees studied in the field at Lageren, Switzerland. All tree species
responded equally in their relative maximum TWD to the onset of declining soil
moisture. This implies that the water supply of all tree species was affected by
declining soil moisture and that none of the four species was able to fully
maintain its water status, e.g., by access to alternative water sources in the
soil. In contrast we found strong and highly species-specific responses of sap
flow to declining soil moisture with the strongest decline in P. abies (92%),
followed by F. sylvatica (53%) and A. pseudoplatanus (48%). F. excelsior did not
significantly reduce sap flow. We hypothesize the species-specific responses in
sap flow to declining soil moisture that occur despite a simultaneous increase in
relative TWD in all species reflect how fast these species approach critical
levels of their water status, which is most likely influenced by species-specific
traits determining the hydraulic properties of the species tree.
PMID- 27609805
TI - Partitioning of vessel resistivity in three liana species.
AB - Vessels with simple perforation plates, found in the majority of angiosperms, are
considered the evolutionarily most advanced conduits, least impeding the xylem
sap flow. Nevertheless, when measured, their hydraulic resistivity (R, i.e.,
inverse value of hydraulic conductivity) is significantly higher than resistivity
predicted using Hagen-Poiseuille equation (RHP). In our study we aimed (i) to
quantify two basic components of the total vessel resistivity - vessel lumen
resistivity and end wall resistivity, and (ii) to analyze how the variable inner
diameter of the vessel along its longitudinal axis affects resistivity. We
measured flow rates through progressively shortened stems of hop (Humulus lupulus
L.), grapevine (Vitis vinifera L.), and clematis (Clematis vitalba L.) and used
elastomer injection for identification of open vessels and for measurement of
changing vessel inner diameters along its axis. The relative contribution of end
wall resistivity to total vessel resistivity was 0.46 for hop, 0.55 for
grapevine, and 0.30 for clematis. Vessel lumen resistivity calculated from our
measurements was substantially higher than theoretical resistivity - about 43%
for hop, 58% for grapevine, and 52% for clematis. We identified variation in the
vessel inner diameter as an important source of vessel resistivity. The
coefficient of variation of vessel inner diameter was a good predictor for the
increase of the ratio of integral RHP to RHP calculated from the mean value of
inner vessel diameter. We discuss the fact that we dealt with the longest vessels
in a given stem sample, which may lead to the overestimation of vessel lumen
resistivity, which consequently precludes decision whether the variable vessel
inner diameter explains fully the difference between vessel lumen resistivity and
RHP we observed.
PMID- 27609806
TI - Viral proliferation and expression of tumor-related gene in different chicken
embryo fibroblasts infected with different tumorigenic phenotypes of avian
leukosis virus subgroup J.
AB - Subgroup J avian leukosis virus (ALV-J) causes a neoplastic disease in infected
chickens. The ALV-J strain NX0101, which was isolated from broiler breeders in
2001, mainly induced formation of myeloid cell tumors. However, strain HN10PY01,
which was recently isolated from laying hens, mainly induces formation of myeloid
cell tumors and hemangioma. To identify the molecular pathological mechanism
underlying changes in host susceptibility and tumor classification induced by
these two types of ALV-J strains, chicken embryo fibroblasts derived from
chickens with different genetic backgrounds (broiler breeders and laying hens)
and an immortalized chicken embryo fibroblasts (DF-1) were prepared and infected
with strain NX0101 or HN10PY01, respectively. The 50% tissue culture infective
dose (TCID50) and levels of ALV group-specific antigen p27 and heat shock protein
70 in the supernatant collected from the ALV-J infected cells were detected.
Moreover, mRNA expression levels of tumor-related genes p53, c-myc, and Bcl-2 in
ALV-J-infected cells were quantified. The results indicated that the infection of
ALV-J could significantly increase mRNA expression levels of p53, c-myc, and Bcl
2 Strain HN10PY01 exhibited a greater influence on the three tumor-related genes
in each of the three types of cells when compared with strain NX0101, and the
TCID50 and p27 levels in the supernatant collected from HN10PY01-infected cells
were higher than those collected from NX0101-infected cells. These results
indicate that the infection of the two ALV-J strains influenced the gene
expression levels in the infected cells, while the newly isolated strain HN10PY01
showed higher replication ability in cells and induced higher expression levels
of tumor-related genes in infected cells. Furthermore, virus titers and
expression levels of tumor-related genes and cellular stress responses of cells
with different genetic backgrounds when infected with each of the two ALV-J
strain were different, indicating that genetic backgrounds influenced the
capabilities of the virus to infect and proliferate. The findings of this study
provide useful data to further elucidate the mechanism underlying host
susceptibility and tumor classification in ALV-J-infected chickens and cells.
PMID- 27609807
TI - Antimicrobial Resistance Among Nontyphoidal Salmonella Isolated From Blood in the
United States, 2003-2013.
AB - BACKGROUND: Salmonella causes an estimated 100 000 antimicrobial-resistant
infections annually in the United States. Salmonella antimicrobial resistance may
result in bacteremia and poor outcomes. We describe antimicrobial resistance
among nontyphoidal Salmonella blood isolates, using data from the National
Antimicrobial Resistance Monitoring System. METHODS: Human nontyphoidal
Salmonella isolates from 2003 to 2013 were classified as fully susceptible,
resistant to >=1 antimicrobial agent, or resistant to a first-line agent.
Logistic regression was used to compare resistance patterns, serotypes, and
patient characteristics for Salmonella isolated from blood versus stool and to
determine resistance trends over time. RESULTS: Approximately 20% of blood
isolates had antimicrobial resistance to a first-line treatment agent. Bacteremia
was associated with male sex, age >=65 years, and specific serotypes. Blood
isolates were more likely to be resistant to >=1 agent for serotypes Enteritidis,
Javiana, Panama, and Typhimurium. Blood isolates were most commonly resistant to
tetracycline (19%), and more likely resistant to a first-line agent (odds ratio,
1.81; 95% confidence interval, 1.56-2.11) than stool isolates. Ceftriaxone
resistance increased in blood isolates from 2003 to 2013 (odd ratio, 1.12; 95%
confidence interval, 1.02-1.22). CONCLUSIONS: Resistance to first-line treatment
agents in patients with Salmonella bacteremia is a concern for public health and
for informing clinical decisions. Judicious antimicrobial use is crucial to limit
resistance.
PMID- 27609808
TI - Viral and Host Responses After Stopping Long-term Nucleos(t)ide Analogue Therapy
in HBeAg-Negative Chronic Hepatitis B.
AB - This prospective study investigated viral and host markers after stopping long
term therapy with nucleos(t)ide analogues in noncirrhotic patients with hepatitis
B e antigen-negative chronic hepatitis B. After stopping therapy, 13 of 15
patients experienced a virological relapse. Rebound of hepatitis B virus DNA and
hepatitis B core-related antigen was associated with induction of plasma tumor
necrosis factor, interleukin (IL) 10 , IL-12p70, CXCL10 and subsequent decline in
hepatitis B surface antigen (HBsAg), with 20% HBsAg loss after long-term follow
up. The peak levels of hepatitis B virus DNA and hepatitis B core-related antigen
after cessation of therapy were positively correlated with the level of HBsAg
decline at week 48. Thus, stopping or interrupting NA treatment should be further
investigated as a strategy to accelerate HBsAg loss.
PMID- 27609810
TI - Non-invasive detection and successful treatment of a Helicobacter pylori
infection in a captive rhesus macaque.
AB - Gastritis is a commonly diagnosed condition in non-human primates used in
biomedical research. As in humans, Helicobacter pylori infection may cause
gastritis. The following report presents a method of non-invasive detection and a
successful treatment protocol for this common pathogen.
PMID- 27609809
TI - Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic Influenza Vaccine
in a Randomized Trial in Healthy Adults.
AB - BACKGROUND: Almost 700 cases of human infection with avian influenza A/H7N9 have
been reported since 2013. Pandemic preparedness strategies include H7N9 vaccine
development. METHODS: We evaluated an inactivated H7N9 vaccine in an observer
blind study in healthy adults aged 18-64 years. Participants (420) were
randomized to receive 1 of 4 AS03-adjuvanted vaccines (low or medium dose of
hemagglutinin with AS03A or AS03B), one nonadjuvanted vaccine, or placebo. The
coprimary immunogenicity objective determined whether adjuvanted vaccines
elicited an immune response against the vaccine-homologous virus, 21 days after
the second vaccine dose per US and European licensure criteria in the per
protocol cohort (n = 389). RESULTS: All adjuvanted vaccines met regulatory
acceptance criteria. In groups receiving adjuvanted formulations, seroconversion
rates were >=85.7%, seroprotection rates >=91.1%, and geometric mean titers
>=92.9% versus 23.2%, 28.6%, and 17.2 for the nonadjuvanted vaccine. The AS03
adjuvant enhanced immune response at antigen-sparing doses. Injection site pain
occurred more frequently with adjuvanted vaccines (in <=98.3% of vaccinees) than
with the nonadjuvanted vaccine (40.7%) or placebo (20.0%). None of the 20 serious
adverse events reported were related to vaccination. CONCLUSIONS: Two doses of
AS03-adjuvanted H7N9 vaccine were well tolerated and induced a robust antibody
response at antigen-sparing doses in healthy adults. CLINICAL TRIALS
REGISTRATION: NCT01999842.
PMID- 27609812
TI - Pathways to sympathies for violent protest and terrorism.
AB - BACKGROUND: Radicalisation is proposed to explain why some individuals begin to
support and take part in violent extremism. However, there is little empirical
population research to inform prevention, and insufficient attention to the role
of psychiatric vulnerabilities. AIMS: To test the impact of depressive symptoms,
adverse life events and political engagement on sympathies for violent protest
and terrorism (SVPT). METHOD: A cross-sectional survey of a representative sample
of Pakistani and Bangladeshi men and women from two English cities. Weighted,
multivariable, logistic regression yielded population estimates of association
(odds ratio (OR) and 95% confidence intervals) against a binary outcome of SVPT
derived from a three-group solution following cluster analysis. RESULTS:
Depressive symptoms were associated with a higher risk of SVPT (OR = 2.59, 95% CI
1.59-4.23, P<0.001), but mediated little of the overall effects of life events
and political engagement, which were associated with a lower risk of SVPT (death
of a close friend: OR = 0.24, 95% CI 0.07-0.74; donating money to a charity: OR =
0.52, 95% CI 0.3-0.9). CONCLUSIONS: Independent of SVPT associations with
depressive symptoms, some expressions of social connectedness (measured as life
events and political engagement) are associated with a lower risk of SVPT.
PMID- 27609811
TI - Prevalence of mental disorders in elderly people: the European MentDis_ICF65+
study.
AB - BACKGROUND: Except for dementia and depression, little is known about common
mental disorders in elderly people. AIMS: To estimate current, 12-month and
lifetime prevalence rates of mental disorders in different European and
associated countries using a standardised diagnostic interview adapted to measure
the cognitive needs of elderly people. METHOD: The MentDis_ICF65+ study is based
on an age-stratified, random sample of 3142 older men and women (65-84 years)
living in selected catchment community areas of participating countries. RESULTS:
One in two individuals had experienced a mental disorder in their lifetime, one
in three within the past year and nearly one in four currently had a mental
disorder. The most prevalent disorders were anxiety disorders, followed by
affective and substance-related disorders. CONCLUSIONS: Compared with previous
studies we found substantially higher prevalence rates for most mental disorders.
These findings underscore the need for improving diagnostic assessments adapted
to the cognitive capacity of elderly people. There is a need to raise awareness
of psychosocial problems in elderly people and to deliver high-quality mental
health services to these individuals.
PMID- 27609813
TI - Exercise and internet-based cognitive-behavioural therapy for depression:
multicentre randomised controlled trial with 12-month follow-up.
AB - BACKGROUND: Evidence-based treatment of depression continues to grow, but
successful treatment and maintenance of treatment response remains limited. AIMS:
To compare the effectiveness of exercise, internet-based cognitive-behavioural
therapy (ICBT) and usual care for depression. METHOD: A multicentre, three-group
parallel, randomised controlled trial was conducted with assessment at 3 months
(post-treatment) and 12 months (primary end-point). Outcome assessors were masked
to group allocation. Computer-generated allocation was performed externally in
blocks of 36 and the ratio of participants per group was 1:1:1. In total, 945
adults with mild to moderate depression aged 18-71 years were recruited from
primary healthcare centres located throughout Sweden. Participants were randomly
assigned to one of three 12-week interventions: supervised group exercise,
clinician-supported ICBT or usual care by a physician. The primary outcome was
depression severity assessed by the Montgomery-Asberg Depression Rating Scale
(MADRS). RESULTS: The response rate at 12-month follow-up was 84%. Depression
severity reduced significantly in all three treatment groups in a quadratic trend
over time. Mean differences in MADRS score at 12 months were 12.1 (ICBT), 11.4
(exercise) and 9.7 (usual care). At the primary end-point the group * time
interaction was significant for both exercise and ICBT. Effect sizes for both
interventions were small to moderate. CONCLUSIONS: The long-term treatment
effects reported here suggest that prescribed exercise and clinician-supported
ICBT should be considered for the treatment of mild to moderate depression in
adults.
PMID- 27609814
TI - Oncogenic p95HER2 regulates Na+-HCO3- cotransporter NBCn1 mRNA stability in
breast cancer cells via 3'UTR-dependent processes.
AB - The Na+-HCO3- cotransporter NBCn1 (SLC4A7) is up-regulated in breast cancer,
important for tumor growth, and a single nucleotide polymorphism (SNP),
rs4973768, in its 3' untranslated region (3'UTR) correlates with increased breast
cancer risk. We previously demonstrated that NBCn1 expression and promoter
activity are strongly increased in breast cancer cells expressing a
constitutively active oncogenic human epidermal growth factor receptor 2 (HER2)
(p95HER2). Here, we address the roles of p95HER2 in regulating NBCn1 expression
via post-transcriptional mechanisms. p95HER2 expression in MCF-7 cells reduced
the rate of NBCn1 mRNA degradation. The NBCn1 3'UTR down-regulated luciferase
reporter expression in control cells, and this was reversed by p95HER2,
suggesting that p95HER2 counteracts 3'UTR-mediated suppression of NBCn1
expression. Truncation analyses identified three NBCn1 3'UTR regions of
regulatory importance. Mutation of putative miRNA-binding sites (miR-374a/b, miR
200b/c, miR-29a/b/c, miR-488) in these regions did not have significant impact on
3'UTR activity. The NBCn1 3'UTR interacted directly with the RNA-binding protein
human antigen R (HuR), and HuR knockdown reduced NBCn1 expression. Conversely,
ablation of a distal AU-rich element increased 3'UTR-driven reporter activity,
suggesting complex regulatory roles of these sites. The cancer-associated SNP
variant decreased reporter expression in T-47D breast cancer cells, yet not in
MCF-7, MDA-MB-231 and SK-BR-3 cells, arguing against a general role in regulating
NBCn1 expression. Finally, p95HER2 expression increased total and plasma membrane
NBCn1 protein levels and decreased the rate of NBCn1 protein degradation.
Collectively, this is the first work to demonstrate 3'UTR-mediated NBCn1
regulation, shows that p95HER2 regulates NBCn1 expression at multiple levels, and
substantiates the central position of p95HER2-NBCn1 signaling in breast cancer.
PMID- 27609815
TI - Modulation of anti-endotoxin property of Temporin L by minor amino acid
substitution in identified phenylalanine zipper sequence.
AB - A 13-residue frog antimicrobial peptide Temporin L (TempL) possesses versatile
antimicrobial activities and is considered a lead molecule for the development of
new antimicrobial agents. To find out the amino acid sequences that influence the
anti-microbial property of TempL, a phenylalanine zipper-like sequence was
identified in it which was not reported earlier. Several alanine-substituted
analogs and a scrambled peptide having the same composition of TempL were
designed for evaluating the role of this motif. To investigate whether leucine
residues instead of phenylalanine residues at 'a' and/or 'd' position(s) of the
heptad repeat sequence could alter its antimicrobial property, several TempL
analogs were synthesized after replacing these phenylalanine residues with
leucine residues. Replacing phenylalanine residues with alanine residues in the
phenylalanine zipper sequence significantly compromised the anti-endotoxin
property of TempL. This is evident from the higher production of tumor necrosis
factor-alpha and interleukin-6 in lipopolysaccharide (LPS)-stimulated rat bone
marrow-derived macrophage cells in the presence of its alanine-substituted
analogs than TempL itself. However, replacement of these phenylalanine residues
with leucine residues significantly augmented anti-endotoxin property of TempL. A
single alanine-substituted TempL analog (F8A-TempL) showed significantly reduced
cytotoxicity but retained the antibacterial activity of TempL, while the two
single leucine-substituted analogs (F5L-TempL and F8L-TempL), although exhibiting
lower cytotoxicity, were able to retain the antibacterial activity of the parent
peptide. The results demonstrate how minor amino acid substitutions in the
identified phenylalanine zipper sequence in TempL could yield analogs with better
antibacterial and/or anti-endotoxin properties with their plausible mechanism of
action.
PMID- 27609817
TI - Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of
Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron
Emission Tomography.
AB - BACKGROUND: Recent evidence suggests that the diagnostic accuracy of myocardial
perfusion imaging is improved by quantifying stress myocardial blood flow (MBF)
in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia
positron emission tomography ((13)NH3-PET) diagnostic panel, including stress
MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction
with relative perfusion defect (PD) assessments to better detect functionally
significant coronary artery stenosis. METHODS AND RESULTS: A total of 130
patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET
and invasive coronary angiography with fractional flow reserve (FFR) measurement.
Diagnostic accuracy, optimal cut points, and discrimination indices of respective
(13)NH3-PET quantitative measures were compared, with FFR as standard reference.
The capacity to discern disease with stepwise addition of stress MBF, CFR, and
RFR to qualitatively assessed relative PD was also gauged, using the category
free net reclassification index. All quantitative measures showed significant
correlation with FFR (PET-derived CFR, r=0.388; stress MBF, r=0.496; and RFR,
r=0.780; all P<0.001). Optimal respective cut points for FFR <=0.8 and <=0.75
were 1.99 and 1.84 mL/min per g for stress MBF and 2.12 and 2.00 for PET-derived
CFR. Discrimination indices of quantitative measures that correlated with FFR
<=0.8 were all significantly higher than that of relative PD (area under the
curve: 0.626, 0.730, 0.806, and 0.897 for relative PD, CFR, stress MBF, and RFR,
respectively; overall comparison P<0.001). The capacity for functionally
significant coronary stenosis was incrementally improved by the successive
addition of CFR (net reclassification index=0.629), stress MBF (net
reclassification index=0.950), and RFR (net reclassification index=1.253; all
P<0.001) to relative PD. CONCLUSIONS: Integrating quantitative (13)NH3-PET
measures with qualitative myocardial perfusion assessment provides superior
diagnostic accuracy and improves the capacity to detect functionally significant
coronary artery stenosis. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifiers: NCT01621438 and NCT01366404.
PMID- 27609818
TI - Left Ventricular Rotational Mechanics in Children After Heart Transplantation.
AB - BACKGROUND: Left ventricular (LV) dysfunction after orthotopic heart
transplantation (OHT) is multifactorial and can be an indicator of graft
rejection or coronary artery vasculopathy. Analysis of rotational mechanics may
help in the early diagnosis of ventricular dysfunction. Studies describing the
left ventricular rotational strain in children after OHT are lacking. It is
important to establish the baseline rotational mechanics in pediatric OHT to
pursue further studies in this population. METHODS AND RESULTS: Rotational strain
measured by speckle tracking was compared in 32 children after OHT, with no
evidence of active rejection or coronary artery vasculopathy with 35 age-matched
normal controls. Twelve OHT patients and 13 controls underwent moderate exercise
with pre- and postexercise echocardiography. Torsion, slope of the systolic limb
of the torsion-radial displacement loop, and the untwist rate were significantly
higher in OHT patients (torsion: median 2.7 degrees /cm [Q1-Q3, 2.3-3.2] versus
2.3 degrees /cm [Q1-Q3, 1.9-2.7]; P=0.03, torsion-radial displacement loop: 2.7
degrees /mm [Q1-Q3, 2.1-3.6] versus 2.0 degrees /mm [Q1-Q3, 1.6-2.7]; P=0.008,
indexed peak untwist rate: -21.6 degrees /s/cm [Q1-Q3, -24.3 to -15.7] versus
17.1 degrees /s/cm [Q1-Q3, -19.6 to -13.3]; P=0.01). Contrary to controls, OHT
recipients were unable to increase torsion with exercise (OHT: 2.8 degrees /cm
[2.7-3.2] versus 3 degrees /cm [2.4-3.5]; P=0.81, controls: 2.2 degrees /cm [2
2.6] versus 3 degrees /cm [2.4-3.7]; P=0.01, pre and post exercise,
respectively). The systolic slope of the torsion-radial displacement loop
relationship decreased with exercise in most OHT patients. CONCLUSIONS: Baseline
rotational strain in OHT patients is higher than normal with a blunted response
to exercise. The slope of torsion-radial displacement loop, and its response to
exercise, may serve as a marker of left ventricular dysfunction in OHT patients.
PMID- 27609816
TI - Long-Term Follow-Up of Outcomes With F-18-Fluorodeoxyglucose Positron Emission
Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular
Dysfunction Secondary to Coronary Disease.
AB - BACKGROUND: Whether viability imaging can impact long-term patient outcomes is
uncertain. The PARR-2 study (Positron Emission Tomography and Recovery Following
Revascularization) showed a nonsignificant trend toward improved outcomes at 1
year using an F-18-fluorodeoxyglucose positron emission tomography (PET)-assisted
strategy in patients with suspected ischemic cardiomyopathy. When patients
adhered to F-18-fluorodeoxyglucose PET recommendations, outcome benefit was
observed. Long-term outcomes of viability imaging-assisted management have not
previously been evaluated in a randomized controlled trial. METHODS AND RESULTS:
PARR-2 randomized patients with severe left ventricular dysfunction and suspected
CAD being considered for revascularization or transplantation to standard care
(n= 195) versus PET-assisted management (n=197) at sites participating in long
term follow-up. The predefined primary outcome was time to composite event
(cardiac death, myocardial infarction, or cardiac hospitalization). After 5
years, 105 (53%) patients in the PET arm and 111 (57%) in the standard care arm
experienced the composite event (hazard ratio for time to composite event =0.82
[95% confidence interval 0.62-1.07]; P=0.15). When only patients who adhered to
PET recommendations were included, the hazard ratio for the time to primary
outcome was 0.73 (95% confidence interval 0.54-0.99; P=0.042). CONCLUSIONS: After
a 5-year follow-up in patients with left ventricular dysfunction and suspected
CAD, overall, PET-assisted management did not significantly reduce cardiac events
compared with standard care. However, significant benefits were observed when
there was adherence to PET recommendations. PET viability imaging may be best
applied when there is likely to be adherence to imaging-based recommendations.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT00385242.
PMID- 27609819
TI - Echocardiographic Structure and Function in Hypertensive Disorders of Pregnancy:
A Systematic Review.
AB - BACKGROUND: Echocardiography is commonly used to direct the management of
hypertensive disorders in medical patients, but its application in pregnancy is
unclear. Our objective was to define the use of echocardiography in pregnancies
complicated by gestational hypertension (GH) and preeclampsia. METHODS AND
RESULTS: We performed a systematic review of articles using an electronic search
of databases from inception to March 2015, prospectively registered with PROSPERO
(CRD42015015700). Eligible studies included pregnant women with GH or
preeclampsia, evaluating left ventricular structure and function using
echocardiography. The search strategy identified 36 studies, including 745 women
with GH and 815 women with preeclampsia. The populations were heterogeneous with
respect to clinical characteristics, parity, and risk of bias. Increased vascular
resistance and left ventricular mass were the most consistent findings in GH and
preeclampsia. Differentiating features from normal pregnancy were left
ventricular wall thickness of >=1.0 cm, exaggerated reduction in E/A, and lateral
e' of <14 cm/s. There was disagreement between studies with regard to cardiac
output because of the timing of echocardiography, although reduced stroke volume
was an indicator of adverse prognosis. Diastolic dysfunction and left ventricular
remodeling are most marked in severe and early-onset preeclampsia, but are also
markers of preeclampsia before clinical manifestation, and are associated with
adverse outcomes. CONCLUSIONS: Echocardiography is a valuable tool to stratify
risk and can guide management and counseling in the preclinical and clinical
phases of GH and preeclampsia. Changes in cardiac function and morphology are
recognizable at an asymptomatic early stage and correlate with disease severity
and adverse outcomes.
PMID- 27609820
TI - Fractional Flow Reserve Returns to Its Origins: Quantitative Cardiac Positron
Emission Tomography.
PMID- 27609821
TI - Echocardiographic Detection of Heart Transplant Graft Dysfunction: A New Twist on
an Old Theme.
PMID- 27609822
TI - Clinical Value of F-18-Fluorodeoxyglucose Positron Emission Tomographic Imaging
of Myocardial Viability Is Dependent on Adherence to Treatment Strategy Based on
Imaging Results.
PMID- 27609823
TI - Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and
attenuates post-infarction cardiac remodelling by inducing engraftment signals.
AB - Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful
reperfusion in patients with acute myocardial infarction (MI) does not improve
cardiac function. The reduction in engraftment signals observed following this
time interval might impair the effects of delayed BMC treatment. In the present
study, we aimed to determine whether ultrasound-targeted microbubble destruction
(UTMD) treatment could increase engraftment signals, enhance the delivery of
delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A
myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left
coronary ligation for 45 min followed by reperfusion. Western blotting revealed
that engraftment signals peaked at 7 days post-I/R and were dramatically lower at
14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be
triggered by UTMD treatment at a mechanical index of 1.0-1.9. The troponin I
levels in the 1.9 mechanical index group were higher than in the other groups.
Simultaneous haematoxylin and eosin staining and fluorescence revealed that the
number of engrafted BMCs in the ischaemic zone was greater in the group treated
with both UTMD and delayed BMC transplantation than in the control groups
(P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and
decreased cardiac fibrosis at 4 weeks after treatment, as compared with control
groups (both P<0.05). Histopathology demonstrated that UTMD combined with delayed
BMC transplantation increased capillary density, myocardial cell proliferation
and c-kit+ cell proliferation. These findings indicated that UTMD treatment could
induce engraftment signals and enhance homing of delayed BMCs to ischaemic
myocardium, attenuating post-infarction cardiac remodelling by promoting
neovascularization, cardiomyogenesis and expansion of cardiac c-kit+ cells.
PMID- 27609824
TI - Pediatric Obsessive-Compulsive Disorder Exacerbation and Obstructive
Hydrocephalus: A Case Report.
AB - We present the case of an 11 year-old boy with a previous history of obsessive
compulsive disorder (OCD), who experienced a dramatic and acute worsening of OCD
symptoms in temporal association with obstructive hydrocephalus secondary to a
tectal low-grade glioma. Management and resolution of the hydrocephalus was
temporally associated with an improvement in his OCD compulsion symptoms. The
present case does not establish proof of cause and effect, but highlights
potential multifactorial influences on OCD onset and clinical course. Cortico
striatal-thalamic-cortical pathways, physically distorted by hydrocephalus in
this case, have long been implicated in OCD etiology. Clinical implications
include the importance of conducting an appropriate neurologic work-up to rule
out biological causes for acute and dramatic OCD exacerbations with neurologic
signs, even in the context of preexisting OCD. Given that neurologic lesions may
exist in the absence of typical signs and symptoms, that they may further disrupt
OCD circuitry, and that treatment may lead to resolution of associated
psychiatric symptoms, it is important to remain cognizant of these differential
diagnoses.
PMID- 27609825
TI - The Bilirubin Binding Panel: A Henderson-Hasselbalch Approach to Neonatal
Hyperbilirubinemia.
AB - Poor plasma bilirubin binding increases the risk of bilirubin neurotoxicity in
newborns with hyperbilirubinemia. New laboratory tests may soon make it possible
to obtain a complete bilirubin binding panel when evaluating these babies. The 3
measured components of the panel are the plasma total bilirubin concentration
(BTotal), which is currently used to guide clinical care; the bilirubin binding
capacity (BBC); and the concentration of non-albumin bound or free bilirubin
(BFree). The fourth component is the bilirubin-albumin equilibrium dissociation
constant, KD, which is calculated from BTotal, BBC, and BFree The bilirubin
binding panel is comparable to the panel of components used in the Henderson
Hasselbalch approach to acid-base assessment. Bilirubin binding population
parameters (not prospective studies to determine whether the new bilirubin
binding panel components are better predictors of bilirubin neurotoxicity than
BTotal) are needed to expedite the clinical use of bilirubin binding. At any
BTotal, the BFree and the relative risk of bilirubin neurotoxicity increase as
the KD/BBC ratio increases (ie, bilirubin binding worsens). Comparing the KD/BBC
ratio of newborns with BTotal of concern with that typical for the population
helps determine whether the risk of bilirubin neurotoxicity varies significantly
from the inherent risk at that BTotal Furthermore, the bilirubin binding panel
individualizes care because it helps to determine how aggressive intervention
should be at any BTotal, irrespective of whether it is above or below established
BTotal guidelines. The bilirubin binding panel may reduce anxiety, costs,
unnecessary treatment, and the likelihood of undetected bilirubin neurotoxicity.
PMID- 27609826
TI - Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring.
AB - OBJECTIVES: To investigate the association between maternal pre-pregnancy BMI and
risk of cerebral palsy (CP) in offspring. METHODS: The study population consisted
of 188 788 children in the Mothers and Babies in Norway and Denmark CP study,
using data from 2 population-based, prospective birth cohorts: the Norwegian
Mother and Child Cohort Study and the Danish National Birth Cohort. Prepregnancy
BMI was classified as underweight (BMI <18.5), lower normal weight (BMI 18.5
22.9), upper normal weight (BMI 23.0-24.9), overweight (BMI 25.0-29.9), and obese
(BMI >=30). CP diagnoses were obtained from the national CP registries.
Associations between maternal prepregnancy BMI and CP in offspring were
investigated by using log-binomial regression models. RESULTS: The 2 cohorts had
390 eligible cases of CP (2.1 per 1000 live-born children). Compared with mothers
in the lower normal weight group, mothers in the upper normal group had a 40%
excess risk of having a child with CP (relative risk [RR], 1.35; 95% confidence
interval [CI], 1.03-1.78). Excess risk was 60% (RR, 1.56; 95% CI, 1.21-2.01) for
overweight mothers and 60% (RR, 1.55; 95% CI 1.11-2.18) for obese mothers. The
risk of CP increased ~4% for each unit increase in BMI (RR, 1.04; 95% CI, 1.02
1.06). Estimates changed little with adjustment for mother's occupational status,
age, and smoking habits. CONCLUSIONS: Higher prepregnancy maternal BMI was
associated with increased risk of CP in offspring.
PMID- 27609827
TI - An unusual endoscopic ultrasound diagnosis in kidney-transplant patient.
PMID- 27609829
TI - Don't mistake it as a polyp!
PMID- 27609828
TI - Extracellular lipid-free apolipoprotein E inhibits HCV replication and induces
ABCG1-dependent cholesterol efflux.
AB - OBJECTIVE: The HCV life cycle and the lipid metabolism are inextricably
intertwined. In the blood, HCV virions are associated with lipoproteins, forming
lipoviroparticles (LVPs), which are the most infectious form of the virus.
Apolipoprotein E (apoE), a key LVP component, plays an essential role in HCV
entry, assembly and egress. ApoE is also a cell host factor involved in
lipoprotein homeostasis. Although the majority of apoE is associated with
lipoproteins, a lipid-free (LF) form exists in blood. However, the role of LF
apoE in both lipid metabolism and HCV life cycle is poorly understood. DESIGN: In
this study, using the cell culture-derived HCV model system in human hepatoma
Huh7.5.1 cells and primary human hepatocytes (PHH), we investigated the effect of
LF-apoE on the early steps of HCV life cycle and on the lipid metabolism of
hepatic cells. RESULTS: A dose-dependent decrease in HCV replication was observed
when Huh7.5.1 cells and PHH were treated with increasing amounts of LF-apoE. We
showed that LF-apoE acts on HCV replication independently of previously described
apoE receptors. We observed that LF-apoE induced a marked hepatic cholesterol
efflux via the ATP-binding cassette subfamily G member 1 (ABCG1) protein that in
turn inhibits HCV replication. LF-apoE also increases both apolipoprotein AI and
high-density lipoprotein production. CONCLUSIONS: Our findings highlight a new
mechanism in lipid metabolism regulation and interaction of the lipid metabolism
with the HCV life cycle, which may be important for viral pathogenesis and might
also be explored for antiviral therapy.
PMID- 27609831
TI - Coronary Plaque Characteristics Associated With Reduced TIMI (Thrombolysis in
Myocardial Infarction) Flow Grade in Patients With ST-Segment-Elevation
Myocardial Infarction: A Combined Optical Coherence Tomography and Intravascular
Ultrasound Study.
AB - BACKGROUND: Previous studies reported that reduced TIMI (Thrombolysis in
Myocardial Infarction) flow grade before procedure was associated with worse
clinical outcomes in patients with ST-segment-elevation myocardial infarction
undergoing primary percutaneous coronary intervention. The aim of this study was
to identify specific morphological characteristics of the culprit plaque
associated with poor TIMI flow grade at baseline in patients with ST-segment
elevation myocardial infarction using both optical coherence tomography and
intravascular ultrasound. METHODS AND RESULTS: A total of 111 ST-segment
elevation myocardial infarction patients who underwent percutaneous coronary
intervention within 24 hours of symptom onset were included. Both optical
coherence tomography and intravascular ultrasound were performed after
thrombectomy. Patients were divided into 2 groups according to preprocedural TIMI
flow grade (TIMI 0-1 [n=82] and TIMI 2-3 [n=29]). Patients with preprocedural
TIMI 0 to 1 had a greater lipid arc (P=0.037), a longer lipid length (P=0.021),
and a greater lipid index (P=0.007) determined by optical coherence tomography
and a larger external elastic membrane cross-sectional area (P=0.030) and plaque
plus media cross-sectional area (P=0.030) determined by intravascular ultrasound,
compared with patients with preprocedural TIMI 2 to 3. CONCLUSIONS: ST-segment
elevation myocardial infarction patients with reduced TIMI flow grade at baseline
have greater lipid burden, larger vessel sizes, and larger plaque areas.
PMID- 27609830
TI - Subclonal diversity arises early even in small colorectal tumours and contributes
to differential growth fates.
AB - OBJECTIVE AND DESIGN: The goal of the study was to determine whether the
mutational profile of early colorectal polyps correlated with growth behaviour.
The growth of small polyps (6-9 mm) that were first identified during routine
screening of patients was monitored over time by interval imaging with CT
colonography. Mutations in these lesions with known growth rates were identified
by targeted next-generation sequencing. The timing of mutational events was
estimated using computer modelling and statistical inference considering several
parameters including allele frequency and fitness. RESULTS: The mutational
landscape of small polyps is varied both within individual polyps and among the
group as a whole but no single alteration was correlated with growth behaviour.
Polyps carried 0-3 pathogenic mutations with the most frequent being in APC,
KRAS/NRAS, BRAF, FBXW7 and TP53. In polyps with two or more pathogenic mutations,
allele frequencies were often variable, indicating the presence of multiple
populations within a single tumour. Based on computer modelling, detectable
mutations occurred at a mean polyp size of 30+/-35 crypts, well before the tumour
is of a clinically detectable size. CONCLUSIONS: These data indicate that small
colon polyps can have multiple pathogenic mutations in crucial driver genes that
arise early in the existence of a tumour. Understanding the molecular pathway of
tumourigenesis and clonal evolution in polyps that are at risk for progressing to
invasive cancers will allow us to begin to better predict which polyps are more
likely to progress into adenocarcinomas and which patients are at greater risk of
developing advanced disease.
PMID- 27609832
TI - Skeletal Muscle Alterations Are Exacerbated in Heart Failure With Reduced
Compared With Preserved Ejection Fraction: Mediated by Circulating Cytokines?
AB - BACKGROUND: A greater understanding of the different underlying mechanisms
between patients with heart failure with reduced (HFrEF) and with preserved
(HFpEF) ejection fraction is urgently needed to better direct future treatment.
However, although skeletal muscle impairments, potentially mediated by
inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying
cellular and molecular alterations that exist between groups are yet to be
systematically evaluated. The present study, therefore, used established animal
models to compare whether alterations in skeletal muscle (limb and respiratory)
were different between HFrEF and HFpEF, while further characterizing inflammatory
cytokines. METHODS AND RESULTS: Rats were assigned to (1) HFrEF (ligation of the
left coronary artery; n=8); (2) HFpEF (high-salt diet; n=10); (3) control (con:
no intervention; n=7). Heart failure was confirmed by echocardiography and
invasive measures. Soleus tissue in HFrEF, but not in HFpEF, showed a significant
increase in markers of (1) muscle atrophy (ie, MuRF1, calpain, and ubiquitin
proteasome); (2) oxidative stress (ie, higher nicotinamide adenine dinucleotide
phosphate oxidase but lower antioxidative enzyme activities); (3) mitochondrial
impairments (ie, a lower succinate dehydrogenase/lactate dehydrogenase ratio and
peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression).
The diaphragm remained largely unaffected between groups. Plasma concentrations
of circulating cytokines were significantly increased in HFrEF for tumor necrosis
factor-alpha, whereas interleukin-1beta and interleukin-12 were higher in HFpEF.
CONCLUSIONS: Our findings suggest, for the first time, that skeletal muscle
alterations are exacerbated in HFrEF compared with HFpEF, which predominantly
reside in limb, rather than in respiratory, muscle. This disparity may be
mediated, in part, by the different circulating inflammatory cytokines that were
elevated between HFpEF and HFrEF.
PMID- 27609833
TI - A basal cell defect promotes budding of prostatic intraepithelial neoplasia.
AB - Basal cells in a simple secretory epithelium adhere to the extracellular matrix
(ECM), providing contextual cues for ordered repopulation of the luminal cell
layer. Early high-grade prostatic intraepithelial neoplasia (HG-PIN) tissue has
enlarged nuclei and nucleoli, luminal layer expansion and genomic instability.
Additional HG-PIN markers include loss of alpha6beta4 integrin or its ligand
laminin-332, and budding of tumor clusters into laminin-511-rich stroma. We
modeled the invasive budding phenotype by reducing expression of alpha6beta4
integrin in spheroids formed from two normal human stable isogenic prostate
epithelial cell lines (RWPE-1 and PrEC 11220). These normal cells continuously
spun in culture, forming multicellular spheroids containing an outer laminin-332
layer, basal cells (expressing alpha6beta4 integrin, high-molecular-weight
cytokeratin and p63, also known as TP63) and luminal cells that secrete PSA (also
known as KLK3). Basal cells were optimally positioned relative to the laminin-332
layer as determined by spindle orientation. beta4-integrin-defective spheroids
contained a discontinuous laminin-332 layer corresponding to regions of abnormal
budding. This 3D model can be readily used to study mechanisms that disrupt
laminin-332 continuity, for example, defects in the essential adhesion receptor
(beta4 integrin), laminin-332 or abnormal luminal expansion during HG-PIN
progression.
PMID- 27609835
TI - Plant mitochondria contain the protein translocase subunits TatB and TatC.
AB - Twin-arginine translocation (Tat) pathways have been well-characterized in
bacteria and chloroplasts. Genes encoding a TatC protein are found in almost all
plant mitochondrial genomes but to date these have not been extensively
investigated. For the first time it could be demonstrated that this mitochondrial
encoded TatC is a functional gene that is translated into a protein in the model
plant Arabidopsis thaliana A TatB--like subunit localized to the inner membrane
was also identified that is nuclear-encoded and is essential for plant growth and
development, indicating that plants potentially require a Tat pathway for
mitochondrial biogenesis.
PMID- 27609834
TI - Calsequestrin interacts directly with the cardiac ryanodine receptor luminal
domain.
AB - Cardiac muscle contraction requires sarcoplasmic reticulum (SR) Ca2+ release
mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2),
calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin. Here, we
demonstrate that a direct interaction exists between RyR2 and CSQ2.
Topologically, CSQ2 binding occurs at the first luminal loop of RyR2. Co
expression of RyR2 and CSQ2 in a human cell line devoid of the other quaternary
complex proteins results in altered Ca2+-release dynamics compared to cells
expressing RyR2 only. These findings provide a new perspective for understanding
the SR luminal Ca2+ sensor and its involvement in cardiac physiology and disease.
PMID- 27609836
TI - Anaphase asymmetry and dynamic repositioning of the division plane during maize
meiosis.
AB - The success of an organism is contingent upon its ability to transmit genetic
material through meiotic cell division. In plant meiosis I, the process begins in
a large spherical cell without physical cues to guide the process. Yet, two
microtubule-based structures, the spindle and phragmoplast, divide the
chromosomes and the cell with extraordinary accuracy. Using a live-cell system
and fluorescently labeled spindles and chromosomes, we found that the process
self- corrects as meiosis proceeds. Metaphase spindles frequently initiate
division off-center, and in these cases anaphase progression is asymmetric with
the two masses of chromosomes traveling unequal distances on the spindle. The
asymmetry is compensatory, such that the chromosomes on the side of the spindle
that is farthest from the cell cortex travel a longer distance at a faster rate.
The phragmoplast forms at an equidistant point between the telophase nuclei
rather than at the original spindle mid-zone. This asymmetry in chromosome
movement implies a structural difference between the two halves of a bipolar
spindle and could allow meiotic cells to dynamically adapt to errors in metaphase
and accurately divide the cell volume.
PMID- 27609837
TI - RNA-binding protein HuR regulates nuclear import of protein.
AB - The RNA-binding protein HuR binds to elements rich in adenylate and uridylate (AU
rich elements) in target mRNAs and stabilizes them against degradation. The
complete spectrum of genes whose expression is regulated by HuR and are the basis
for the broad range of cellular functions of the protein is incompletely
understood. We show that HuR controls the expression of multiple components of
the nuclear import machinery. Consequently, HuR is crucial for the nuclear import
of cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to the
nuclear retinoic acid receptor (RAR) and whose mobilization to the nucleus is
mediated by a 'classical-like' nuclear localization signal (NLS). HuR is also
required for heregulin-induced nuclear translocation of the NFkappaB subunit p65,
which contains both classical and non-canonical NLSs. HuR thus regulates the
transcriptional activities of both RAR and NFkappaB. The observations reveal that
HuR plays a central role in regulating nuclear import of proteins.
PMID- 27609840
TI - Personalized Medicine Tackles Clinical Resistance: Alectinib in ALK-Positive Non
Small Cell Lung Cancer Progressing on First-Generation ALK Inhibitor.
AB - Over the last 2 years, our therapeutic armamentarium against genomically defined
subgroups of non-small cell lung cancer (NSCLC) has extended to patients with
acquired resistance to front-line targeted therapy. Alectinib (Alecensa;
Roche/Genentech), a second-generation, orally active, potent, and highly
selective inhibitor of anaplastic lymphoma kinase (ALK), is indicated for
patients with metastatic, ALK rearrangement-positive NSCLC whose disease has
worsened after treatment with crizotinib or who became intolerant to the drug.
Alectinib received orphan drug designation, breakthrough therapy designation,
priority review status, and accelerated approval by the FDA. Clin Cancer Res;
22(21); 5177-82. (c)2016 AACR.
PMID- 27609838
TI - Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of
gene expression, cell growth and differentiation.
AB - Tescalcin (TESC, also known as calcineurin-homologous protein 3, CHP3) is a 24
kDa EF-hand Ca2+-binding protein that has recently emerged as a regulator of cell
differentiation and growth. The TESC gene has also been linked to human brain
abnormalities, and high expression of tescalcin has been found in several
cancers. The expression level of tescalcin changes dramatically during
development and upon signal-induced cell differentiation. Recent studies have
shown that tescalcin is not only subjected to up- or down-regulation, but also
has an active role in pathways that drive cell growth and differentiation
programs. At the molecular level, there is compelling experimental evidence
showing that tescalcin can directly interact with and regulate the activities of
the Na+/H+ exchanger NHE1, subunit 4 of the COP9 signalosome (CSN4) and protein
kinase glycogen-synthase kinase 3 (GSK3). In hematopoetic precursor cells,
tescalcin has been shown to couple activation of the extracellular signal
regulated kinase (ERK) cascade to the expression of transcription factors that
control cell differentiation. The purpose of this Commentary is to summarize
recent efforts that have served to characterize the biochemical, genetic and
physiological attributes of tescalcin, and its unique role in the regulation of
various cellular functions.
PMID- 27609839
TI - Dynamic Interactions of Arabidopsis TEN1: Stabilizing Telomeres in Response to
Heat Stress.
AB - Telomeres are the essential nucleoprotein structures that provide a physical cap
for the ends of linear chromosomes. The highly conserved CST (CTC1/STN1/TEN1)
protein complex facilitates telomeric DNA replication and promotes telomere
stability. Here we report three unexpected properties of Arabidopsis thaliana
TEN1 that indicate it possesses functions distinct from other previously
characterized telomere proteins. First, we show that telomeres in ten1 mutants
are highly sensitive to thermal stress. Heat shock causes abrupt and dramatic
loss of telomeric DNA in ten1 plants, likely via deletional recombination.
Second, we show that AtTEN1 has the properties of a heat-shock induced molecular
chaperone. At elevated temperature, AtTEN1 rapidly assembles into high molecular
weight homo-oligomeric complexes that efficiently suppress heat-induced
aggregation of model protein substrates in vitro. Finally, we report that AtTEN1
specifically protects CTC1 from heat-induced aggregation in vitro, and from heat
induced protein degradation and loss of telomere association in vivo.
Collectively, these observations define Arabidopsis TEN1 as a highly dynamic
protein that works in concert with CTC1 to preserve telomere integrity in
response to environmental stress.
PMID- 27609842
TI - Prevalence of obesity and affecting factors in physically disabled adults living
in the city centre of Malatya.
AB - OBJECTIVE: The purpose of this study was to investigate the prevalence of
obesity, and the risk factors associated with it, in physically disabled adults
living in the city centre of Malatya, Turkey. METHOD: This research was designed
as a cross-sectional study conducted on physically disabled people aged 20-65
years living in the city centre of Malatya. The prevalence of obesity in disabled
people was within 95% CIs, the power was calculated as 80%, and the sample size
of our population was calculated as 258 individuals. RESULTS: The prevalence of
obesity was found to be 13.2%. The relationship between disability type and
obesity status was found to be significant. The prevalence of obesity was 21.3%
in visually impaired people, 17.9% in speech-impaired people, 17.8% in hearing
impaired people and 6.5% in orthopaedically disabled people. CONCLUSIONS:
Educational interventions on nutrition and lifestyle can be effective considering
the high prevalence of obesity in visually impaired people, the prevalence of
weakness in orthopaedically disabled people and the risk related to the area in
which body fat is localised even when body mass index is within the normal range.
Training disabled people in sports appropriate to their disability type and
building appropriate facilities for those sports might have a positive effect.
PMID- 27609841
TI - Imaging Tumor Metabolism to Assess Disease Progression and Treatment Response.
AB - Changes in tumor metabolism may accompany disease progression and can occur
following treatment, often before there are changes in tumor size. We focus here
on imaging methods that can be used to image various aspects of tumor metabolism,
with an emphasis on methods that can be used for tumor grading, assessing disease
progression, and monitoring treatment response. Clin Cancer Res; 22(21); 5196
203. (c)2016 AACR.
PMID- 27609843
TI - Multivariable fractional polynomial interaction to investigate continuous effect
modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.
AB - OBJECTIVES: A recent individual patient data (IPD) meta-analysis suggested that
patients with moderate or severe acute respiratory distress syndrome (ARDS)
benefit from higher positive end-expiratory pressure (PEEP) ventilation
strategies. However, thresholds for continuous variables (eg, hypoxaemia) are
often arbitrary and linearity assumptions in regression approaches may not hold;
the multivariable fractional polynomial interaction (MFPI) approach can address
both problems. The objective of this study was to apply the MFPI approach to
investigate interactions between four continuous patient baseline variables and
higher versus lower PEEP on clinical outcomes. SETTING: Pooled data from three
randomised trials in intensive care identified by a systematic review.
PARTICIPANTS: 2299 patients with acute lung injury requiring mechanical
ventilation. INTERVENTIONS: Higher (N=1136) versus lower PEEP (N=1163)
ventilation strategy. OUTCOME MEASURES: Prespecified outcomes included mortality,
time to death and time-to-unassisted breathing. We examined the following
continuous baseline characteristics as potential effect modifiers using MFPI:
PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen),
oxygenation index, respiratory system compliance (tidal volume/(inspiratory
plateau pressure-PEEP)) and body mass index (BMI). RESULTS: We found that for
patients with PaO2/FiO2 below 150 mm Hg, but above 100 mm Hg or an oxygenation
index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the
beneficial effect appears to level off for patients with very severe ARDS.
Patients with mild ARDS (PaO2/FiO2 above 200 mm Hg or an oxygenation index below
10) do not seem to benefit from higher PEEP and might even be harmed. For
patients with a respiratory system compliance above 40 mL/cm H2O or patients with
a BMI above 35 kg/m(2), we found a trend towards reduced mortality with higher
PEEP, but there is very weak statistical confidence in these findings.
CONCLUSIONS: MFPI analyses suggest a nonlinear effect modification of higher PEEP
ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some
patients suffering from moderate ARDS. STUDY REGISTRATION NUMBER: CRD42012003129.
PMID- 27609844
TI - Understanding negative feedback from South Asian patients: an experimental
vignette study.
AB - OBJECTIVES: In many countries, minority ethnic groups report poorer care in
patient surveys. This could be because they get worse care or because they
respond differently to such surveys. We conducted an experiment to determine
whether South Asian people in England rate simulated GP consultations the same or
differently from White British people. If these groups rate consultations
similarly when viewing identical simulated consultations, it would be more likely
that the lower scores reported by minority ethnic groups in real surveys reflect
real differences in quality of care. DESIGN: Experimental vignette study. Trained
fieldworkers completed computer-assisted personal interviews during which
participants rated 3 video recordings of simulated GP-patient consultations,
using 5 communication items from the English GP Patient Survey. Consultations
were shown in a random order, selected from a pool of 16. SETTING: Geographically
confined areas of ~130 households (output areas) in England, selected using
proportional systematic sampling. PARTICIPANTS: 564 White British and 564
Pakistani adults recruited using an in-home face-to-face approach. MAIN OUTCOME
MEASURE: Mean differences in communication score (on a scale of 0-100) between
White British and Pakistani participants, estimated from linear regression.
RESULTS: Pakistani participants, on average, scored consultations 9.8 points
higher than White British participants (95% CI 8.0 to 11.7, p<0.001) when viewing
the same consultations. When adjusted for age, gender, deprivation, self-rated
health and video, the difference increased to 11.0 points (95% CI 8.5 to 13.6,
p<0.001). The largest differences were seen when participants were older (>55)
and where communication was scripted to be poor. CONCLUSIONS: Substantial
differences in ratings were found between groups, with Pakistani respondents
giving higher scores than White British respondents to videos showing the same
care. Our findings suggest that the lower scores reported by Pakistani patients
in national surveys represent genuinely worse experiences of communication
compared to the White British majority.
PMID- 27609845
TI - Long-term health effects of the Eyjafjallajokull volcanic eruption: a prospective
cohort study in 2010 and 2013.
AB - OBJECTIVES: To examine the long-term development of physical and mental health
following exposure to a volcanic eruption. DESIGN: Population-based prospective
cohort study. SETTING: In spring 2010, the Icelandic volcano Eyjafjallajokull
erupted. Data were collected at 2 time points: in 2010 and 2013. PARTICIPANTS:
Adult residents in areas close to the Eyjafjallajokull volcano (N=1096), divided
according to exposure levels, and a non-exposed sample (n=475), with 80%
participation rate in 2013. MAIN OUTCOME MEASURES: Physical symptoms in the
previous year (chronic) and previous month (recent), and psychological distress
(General Health Questionnaire-12-item version, GHQ-12), perceived stress
(Perceived Stress Scale, PSS-4) and post traumatic stress disorder (PTSD)
symptoms (Primary Care PTSD, PC-PTSD). RESULTS: In the exposed group, certain
symptoms were higher in 2013 than in 2010, for example, morning phlegm during
winter (OR 2.14; 95% CI 1.49 to 3.06), skin rash/eczema (OR 2.86; 95% CI 1.76 to
4.65), back pain (OR 1.45; 95% CI 1.03 to 2.05) and insomnia (OR 1.53; 95% CI
1.01 to 2.30), in addition to a higher prevalence of regular use of certain
medications (eg, for asthma (OR 2.80; 95% CI 1.01 to 7.77)). PTSD symptoms
decreased between 2010 and 2013 (OR 0.33; 95% CI 0.17 to 0.61), while the
prevalence of psychological distress and perceived stress remained similar. In
2013, the exposed group showed a higher prevalence of various respiratory
symptoms than did the non-exposed group, such as wheezing without a cold (high
exposure OR 2.35; 95% CI 1.27 to 4.47) and phlegm (high exposure OR 2.81; 95% CI
1.48 to 5.55), some symptoms reflecting the degree of exposure (eg, nocturnal
chest tightness (medium exposed OR 3.09; 95% CI 1.21 to 10.46; high exposed OR
3.42; 95% CI 1.30 to 11.79)). CONCLUSIONS: The findings indicate that people
exposed to a volcanic eruption, especially those most exposed, exhibit increased
risk of certain symptoms 3-4 years after the eruption.
PMID- 27609846
TI - Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by
ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with
osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group
trial.
AB - INTRODUCTION: Total knee arthroplasty (TKA) has been regarded as a most painful
orthopaedic surgery. Although many surgeons sequentially use parecoxib and
celecoxib as a routine strategy for postoperative pain control after TKA, high
quality evidence is still lacking to prove the effect of this sequential regimen,
especially at the medium-term follow-up. The purpose of this study, therefore, is
to evaluate efficacy and safety of postoperative intravenous parecoxib sodium
followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA.
The hypothesis is that compared to placebo with opioids as rescue treatment,
sequential use of parecoxib and celecoxib can achieve less morphine consumption
over the postoperative 2 weeks, as well as better pain control, quicker
functional recovery in the postoperative 6 weeks and less opioid-related adverse
events during the 12-week recovery phase. METHODS AND ANALYSIS: This study is
designed as a multicentre, randomised, double-blind, parallel-group and placebo
controlled trial. The target sample size is 246. All participants who meet the
study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio
to either the parecoxib/celecoxib group or placebo group. The randomisation and
allocation will be study site based. The study will consist of three phases: an
initial screening phase; a 6-week double-blind treatment phase; and a 6-week
follow-up phase. The primary end point is cumulative opioid consumption during 2
weeks postoperation. Secondary end points consist of the postoperative visual
analogue scale score, knee joint function, quality of life, local skin
temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and
blood coagulation parameters. Safety end points will be monitored too. ETHICS AND
DISSEMINATION: Ethics approval for this study has been obtained from the Ethics
Committee, Peking Union Medical College Hospital, China (Protocol number: S-572)
Study results will be available as published manuscripts and presentations at
national and international meetings. TRIAL REGISTRATION NUMBER: NCT02198924.
PMID- 27609847
TI - Associations between sitting time and non-alcoholic fatty liver diseases in
Chinese male workers: a cross-sectional study.
AB - OBJECTIVES: Various studies have revealed a close association between sedentary
behaviour and metabolic diseases, yet the association between sedentary time and
non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we
investigated the association between sitting time and NAFLD in a Chinese male
population and explored its underlying mechanism. STUDY DESIGN: A cross-sectional
study. SETTING: Chongqing, China. PARTICIPANTS: Our study included 2054 male
participants; all of the participants were of Han nationality. PRIMARY OUTCOME
MEASURES: Sitting time was assessed using a self-reported questionnaire
concerning the time devoted to sitting behaviour. Various clinical and
demographic biomarkers were measured. Logistic regression analyses were used to
investigate the ORs and the 95% CIs between sitting time and NAFLD. RESULTS: We
found a higher proportion of NAFLD across the tertiles of sitting time (p
trend=0.003). Multivariate linear regression analyses showed sitting time
independently correlated with homoeostasis model assessment for insulin
resistance (HOMA-IR), alanine aminotransferase, gamma-glutamyl transpeptidase,
body mass index, triglyceride and the high-sensitive C reactive protein (hsCRP)
(all p<0.05). Further logistic regression analyses showed that longer sitting
time (>7.1 hours/day) was associated with a higher prevalence of NAFLD (OR 1.09;
95% CI (1.04 to 1.67)) after adjusting for confounders. However, this association
was insignificant after further adjusting for hsCRP (OR 1.03; 95% CI (0.92 to
1.84)). CONCLUSIONS: Sitting time was positively associated with the prevalence
of NAFLD, and this association might be affected by inflammation.
PMID- 27609848
TI - Self-reported knowledge on diabetes and its related factors among Chinese college
students: a cross-sectional study.
AB - OBJECTIVES: An increasing trend in the prevalence of type 2 diabetes has been
observed among youths; however, little is known about how informed young people
are of its existence and dangers. This study is to assess the level of knowledge
on type 2 diabetes among Chinese college students and to explore related factors
influencing the knowledge. SETTING: A cross-sectional survey was conducted among
college students in Guangzhou, China, from September to November 2013.
PARTICIPANTS: A total of 658 students were randomly recruited using a multistage
sampling method and were invited to participate in the confidential interviews.
PRIMARY AND SECONDARY OUTCOME MEASURES: Self-reported knowledge on diabetes and
its main sources were measured by a self-designed questionnaire. RESULTS: A total
of 521 students participated in this study. The mean total score of knowledge was
13.3+/-3.44 of 22. Less than 50% of participants could correctly answer the
questions about the onset of type 2 diabetes, the adverse effects of sedentary
lifestyles, the complications, the therapeutic methods and the monitoring index
of diabetes. The factors associated with higher levels of knowledge about type 2
diabetes in stepwise regression models were: being in a high grade, having a
better academic performance, having a medical specialty and having relatives or
friends with diabetes. Newspapers and books (61.4%), television and the Internet
(46.3%) were the major sources of knowledge about type 2 diabetes, and more than
half of the participants (55.9%) considered that medical staff was the most
reliable source. CONCLUSIONS: The college students had limited knowledge about
type 2 diabetes. Public education, especially among individuals with non-medical
specialties, a low-level grade, poor academic performance or no relatives and
friends with diabetes, would be extremely beneficial.
PMID- 27609850
TI - Gender equity programmes in academic medicine: a realist evaluation approach to
Athena SWAN processes.
AB - OBJECTIVES: Gender inequity has persisted in academic medicine. Yet equity is
vital for countries to achieve their full potential in terms of translational
research and patient benefit. This study sought to understand how the gender
equity programme, Athena SWAN, can be enabled and constrained by interactions
between the programme and the context it is implemented into, and whether these
interactions might produce unintended consequences. DESIGN: Multimethod
qualitative case studies using a realist evaluation approach. SETTING: 5
departments from a university medical school hosting a Translational Research
Organisation. PARTICIPANTS: 25 hours of observations of gender equality committee
meetings, 16 in-depth interviews with Heads of Departments, Committee Leads and
key personnel involved in the initiative. 4 focus groups with 15 postdoctoral
researchers, lecturers and senior lecturers. RESULTS: The implementation of
Athena SWAN principles was reported to have created social space to address
gender inequity and to have highlighted problematic practices to staff. However,
a number of factors reduced the programme's potential to impact gender inequity.
Gender inequity was reproduced in the programme's enactment as female staff was
undertaking a disproportionate amount of Athena SWAN work, with potential
negative impacts on individual women's career progression. Early career
researchers experienced problems accessing Athena SWAN initiatives. Furthermore,
the impact of the programme was perceived to be undermined by wider institutional
practices, national policies and societal norms, which are beyond the programme's
remit. CONCLUSIONS: Gender equity programmes have the potential to address
inequity. However, paradoxically, they can also unintentionally reproduce and
reinforce gender inequity through their enactment. Potential programme impacts
may be undermined by barriers to staff availing of career development and
training initiatives, and by wider institutional practices, national policies and
societal norms.
PMID- 27609849
TI - Psychological impact of injuries sustained in motor vehicle crashes: systematic
review and meta-analysis.
AB - OBJECTIVE: The aim of this meta-analysis was to determine the psychological
impact associated with motor vehicle crash (MVC)-related physical injuries.
DESIGN: Systematic review and meta-analysis. DATA SOURCES: Multiple search
engines included MEDLINE (via OVID), PsycINFO and Embase, and studies were
sourced from scientific journals, conference papers and doctoral theses. STUDY
SELECTION: A high-yield search strategy was employed. Terms like 'psychological
distress', 'depression', 'PTSD' and 'motor vehicle accident' were employed. These
key words were run primarily and secondary searches were then conducted in
association with the major injury types. Studies needed to compare psychological
distress in people injured in an MVC with uninjured controls who had not recently
experienced an MVC. DATA EXTRACTION: Searches resulted in the identification of
2537 articles, and after eliminating duplicates and studies not meeting inclusion
criteria, 24 studies were selected involving 4502 injured participants. These
studies were entered into separate meta-analyses for mild to moderate traumatic
brain injury (mTBI), whiplash-associated disorder (WAD) and spinal cord injury
(SCI). RESULTS: Elevated psychological distress was associated with MVC-related
injuries with a large summary effect size in WAD (0.90), medium to large effect
size in SCI (0.69) and small to medium effect size in mTBI (0.23). No studies
meeting inclusion criteria were found for burns, fractures and low back injury.
Increased psychological distress remains elevated in SCI, mTBI and WAD for at
least 3 years post-MVC. CONCLUSIONS: Rehabilitation strategies are needed to
minimise distress subsequent to MVC-related physical injuries and the scientific
robustness of studies requires improvement.
PMID- 27609851
TI - What is the role of a specialist regional mesothelioma multidisciplinary team
meeting? A service evaluation of one tertiary referral centre in the UK.
AB - BACKGROUND: Multidisciplinary team meetings are standard care for cancer in the
UK and Europe. Professional bodies recommend that mesothelioma cases should be
discussed at specialist multidisciplinary team meetings. However, no evidence
exists exploring the role of the specialist mesothelioma multidisciplinary team
meeting. OBJECTIVES: To evaluate the clinical activity of 1 specialist
mesothelioma multidisciplinary team meeting and to determine how often a
definitive diagnosis was made, whether the core requirements of the meeting were
met and whether there was any associated benefit or detriment. DESIGN AND
SETTING: A service evaluation using routinely collected data from 1 specialist
mesothelioma multidisciplinary team meeting in a tertiary referral hospital in
the South-West of England. PARTICIPANTS: All cases discussed between 1/1/2014 and
31/12/2015. OUTCOME MEASURES: The primary outcome measure was whether a
definitive diagnosis was made. Secondary outcomes included whether treatment
advice was offered, information on clinical trials provided or further
investigations suggested. Additional benefits of the multidisciplinary team
meeting and time taken from referral to outcome were also collected. RESULTS: A
definitive diagnosis was reached in 171 of 210 cases discussed (81%).
Mesothelioma was diagnosed in 153/210 (73%). Treatment advice was provided for
127 of 171 diagnostic cases (74%) and further investigations suggested for all 35
non-diagnostic cases. 86/210 cases (41%) were invited to participate in a trial,
of whom 43/86 (50%) subsequently enrolled. Additional benefits included the
avoidance of postmortem examination if the coroner was satisfied with the
multidisciplinary team decision. The overall process from referral to outcome
dispatch was <2 weeks in 75% of cases. CONCLUSIONS: This specialist mesothelioma
multidisciplinary team meeting was effective at making diagnoses and providing
recommendations for further investigations or treatment. The core requirements of
a specialist mesothelioma multidisciplinary team meeting were met. The process
was timely, with most outcomes returned within 2 weeks of referral.
PMID- 27609852
TI - Cost-efficiency of specialist hyperacute in-patient rehabilitation services for
medically unstable patients with complex rehabilitation needs: a prospective
cohort analysis.
AB - OBJECTIVES: To evaluate functional outcomes, care needs and cost-efficiency of
hyperacute (HA) rehabilitation for a cohort of in-patients with complex
neurological disability and unstable medical/surgical conditions. DESIGN: A
multicentre cohort analysis of prospectively collected clinical data from the UK
Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2012
2015. SETTING: Two HA specialist rehabilitation services in England, providing
different service models for HA rehabilitation. PARTICIPANTS: All patients
admitted to each of the units with an admission rehabilitation complexity M score
of >=3 (N=190; mean age 46 (SD16) years; males:females 63:37%). Diagnoses were
acquired brain injury (n=166; 87%), spinal cord injury (n=9; 5%), peripheral
neurological conditions (n=9; 5%) and other (n=6; 3%). INTERVENTION: Specialist
in-patient multidisciplinary rehabilitation combined with management and
stabilisation of intercurrent medical and surgical problems. OUTCOME MEASURES:
Rehabilitation complexity and medical acuity: Rehabilitation Complexity Scale
version 13. Dependency and care costs: Northwick Park Dependency Scale/Care Needs
Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment
Measure (UK FIM+FAM). PRIMARY OUTCOMES: (1) reduction in dependency and (2) cost
efficiency, measured as the time taken to offset rehabilitation costs by savings
in NPCNA-estimated costs of on-going care in the community. RESULTS: The mean
length of stay was 103 (SD66) days. Some differences were observed between the
two units, which were in keeping with the different service models. However, both
units showed a significant reduction in dependency and acuity between admission
and discharge on all measures (Wilcoxon: p<0.001). For the 180 (95%) patients
with complete NPCNA data, the mean episode cost was L77 119 (bootstrapped 95% CI
L70 614 to L83 894) and the mean reduction in 'weekly care costs' was L462/week
(95% CI 349 to 582). The mean time to offset the cost of rehabilitation was 27.6
months (95% CI 13.2 to 43.8). CONCLUSIONS: Despite its relatively high initial
cost, specialist HA rehabilitation can be highly cost-efficient, producing
substantial savings in on-going care costs, and relieving pressure in the acute
care services.
PMID- 27609853
TI - Prevalence and factors associated with parental concerns about development
detected by the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12
month and 18-month well-child checks in a birth cohort.
AB - OBJECTIVES: Early identification of developmental vulnerability is vital. This
study aimed to estimate the prevalence of moderate or high developmental risk on
the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12-month and
18-month well-child checks; identify associated risk factors; and examine
documentation of the PEDS at well-child checks. DESIGN, PARTICIPANTS: A
prospective birth cohort of 2025 children with 50% of those approached agreeing
to participate. Demographic data were obtained via questionnaires and linked
electronic medical records. Telephone interviews were conducted with parents to
collect PEDS data. PRIMARY AND SECONDARY OUTCOMES: Multiple logistic regression
analyses identified risk factors for moderate or high developmental risk on the
PEDS. A Cumulative Risk Index examined the impact of multiple risk factors on
developmental risk and documentation of the PEDS at the well-child checks.
RESULTS: Of the original cohort, 792 (39%) had 6-month, 649 (32%) had 12-month
and 565 (28%) had 18-month PEDS data. Parental concerns indicating moderate or
high developmental risk on the PEDS were 27% (95% CI 24 to 30) at 6 months, 27%
(95% CI 24 to 30) at 12 months and 33% (95% CI 29 to 37) at 18 months. Factors
associated with moderate or high developmental risk were perinatal risk (OR 12
months: 1.7 (95% CI 1.1 to 2.7)); maternal Middle Eastern or Asian nationality
(OR 6 months: 1.6 (95% CI 1.1 to 2.4)), (OR 12 months: 1.7 (95% CI 1.1 to 2.7));
and household disadvantage (OR 6 months: 1.5 (95% CI 1.0 to 2.2). As the number
of risk factors increased the odds increased for high or moderate developmental
risk and no documentation of the PEDS at well-child checks. CONCLUSIONS: Children
with multiple risk factors are more likely to have parental concerns indicating
developmental vulnerability using the PEDS and for these concerns to not be
documented.
PMID- 27609854
TI - Study protocol of a randomised controlled trial of intranasal ketamine compared
with intranasal fentanyl for analgesia in children with suspected, isolated
extremity fractures in the paediatric emergency department.
AB - INTRODUCTION: Fentanyl is the most widely studied intranasal (IN) analgesic in
children. IN subdissociative (INSD) ketamine may offer a safe and efficacious
alternative to IN fentanyl and may decrease overall opioid use during the
emergency department (ED) stay. This study examines the feasibility of a larger,
multicentre clinical trial comparing the safety and efficacy of INSD ketamine to
IN fentanyl and the potential role for INSD ketamine in reducing total opioid
medication usage. METHODS AND ANALYSIS: This double-blind, randomised controlled,
pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 MUg/kg) for
analgesia in 80 children aged 4-17 years with acute pain from a suspected, single
extremity fracture. The primary safety outcome for this pilot trial will be the
frequency of cumulative side effects and adverse events at 60 min after drug
administration. The primary efficacy outcome will be exploratory and will be the
mean reduction of pain scale scores at 20 min. The study is not powered to
examine efficacy. Secondary outcome measures will include the total dose of
opioid pain medication in morphine equivalents/kg/hour (excluding study drug)
required during the ED stay, number and reason for screen failures, time to
consent, and the number and type of protocol deviations. Patients may receive up
to 2 doses of study drug. ETHICS AND DISSEMINATION: This study was approved by
the US Food and Drug Administration, the local institutional review board and the
study data safety monitoring board. This study data will be submitted for
publication regardless of results and will be used to establish feasibility for a
multicentre, non-inferiority trial. TRIAL REGISTRATION NUMBER: NCT02521415.
PMID- 27609855
TI - Delay to mental healthcare in a cohort of Canadian Armed Forces personnel with
deployment-related mental disorders, 2002-2011: a retrospective cohort study.
AB - OBJECTIVE: To assess whether the delay to care among Canadian Armed Forces (CAF)
personnel who sought care for a mental disorder changed over time and in
association with CAF mental health system augmentations. DESIGN: A stratified,
random sample (n=2014) was selected for study from an Afghanistan-deployed cohort
(N=30 513) and the 415 (weighted N=4108) individuals diagnosed with an
Afghanistan service-related mental disorder were further assessed. Diagnosis
related data were abstracted from medical records (22 June 2010 to 30 May 2011).
Other data were extracted from administrative databases. Delay to care was
assessed across five mental health system eras: 2002/2004, 2005/2006, 2007, 2008
and 2009/2010. Weighted Cox proportional hazards regression assessed the
association between era, handled as a time-dependent covariate, and the outcome
while controlling for a broad range of potential confounders (ie,
sociodemographic, military and clinical characteristics). Taylor series
linearisation methods and sample design weights were applied in generating
descriptive and regression analysis statistics. PRIMARY OUTCOME: The outcome was
the delay to mental healthcare, defined as the latency from most recent
Afghanistan deployment return date to diagnosis date, among individuals with an
Afghanistan service-related mental disorder diagnosis. RESULTS: Mean delay to
care was 551 days (95% CI 501 to 602); the median was 400 days. Delay to care
decreased in subsequent eras relative to 2002/2004; however, only the most recent
era (2009/2010) was statistically significant (adjusted HR (aHR): 3.01 (95% CI
1.91 to 4.73)). Men, operations support occupations, higher ranks, non
musculoskeletal comorbidities and fewer years of military service were also
independently associated with longer delays to care. CONCLUSIONS: CAF mental
health system changes were associated with reduced delays to mental healthcare.
Further evaluation research is needed to identify the key system changes that
were most impactful.
PMID- 27609856
TI - Investigating the effects of 6 months extended duration, in-centre nocturnal
versus conventional haemodialysis treatment: a non-randomised, controlled
feasibility study.
AB - INTRODUCTION: In-centre nocturnal haemodialysis (INHD) is an underutilised
dialysis regimen that can potentially provide patients with better clinical
outcomes due to extended treatment times. We have established an INHD programme
within our clinical network, fulfilling a previously unmet patient need. This
feasibility study aims to gather sufficient data on numerous outcome measures to
inform the design of a multicentre randomised controlled trial that will
establish the potential benefits of INHD and increase the availability of this
service nationally and internationally. METHODS AND ANALYSIS: This will be a non
randomised controlled study. Prevalent patients on haemodialysis (HD) will
electively change from a conventional in-centre HD regimen of 4 hours thrice
weekly to a regimen of extended treatment times (5-8 hours) delivered in-centre
overnight thrice weekly. After recruitment of the INHD cohort, a group of
patients matched for age, gender and dialysis vintage will be selected from
patients remaining on a conventional daytime dialysis programme. Outcome measures
will include left ventricular mass as measured by MRI, physical performance
measured by the short physical performance battery and physical activity measured
by accelerometry. Additionally we will measure quality of life using validated
questionnaires, nutritional status by bioimpedance spectroscopy and food diaries,
and blood sampling for markers of cardiovascular disease, systemic inflammation.
Suitable statistical tests shall be used to analyse the data. We will use omnibus
tests to observe changes over the duration of the intervention and between
groups. We will also look for associations between outcome measures that may
warrant further investigation. These data will be used to inform the power
calculation for future studies. ETHICS AND DISSEMINATION: A favourable opinion
was granted by Northampton Research Ethics Committee (15/EM/0268). It is
anticipated that results of this study will be presented at national and
international meetings, with reports being published in journals during 2017.
TRIAL REGISTRATION NUMBER: ISRCTN16672784.
PMID- 27609857
TI - Burn injury and long-term nervous system morbidity: a population-based cohort
study.
AB - OBJECTIVE: To investigate if children and adults who are hospitalised for a burn
injury have increased long-term hospital use for nervous system diseases. DESIGN:
A population-based retrospective cohort study using linked administrative health
data from the Western Australian Data Linkage System. PARTICIPANTS: Records of 30
997 persons hospitalised for a first burn injury in Western Australia during the
period 1980-2012, and 123 399 persons who were age and gender frequency matched
with no injury admissions randomly selected from Western Australia's birth
registrations and electoral roll. MAIN OUTCOME MEASURES: Admission rates and
summed length of stay for nervous system diseases. Negative binomial and Cox
proportional hazards regression modelling were used to generate incidence rate
ratios (IRRs) and HRs with 95% CIs, respectively. RESULTS: After adjustment for
demographic factors and pre-existing health status, the burn injury cohort had
2.20 times (95% CI 1.86 to 2.61) as many nervous system admissions and 3.25 times
the number of days in hospital (95% CI: 2.28 to 4.64) than the uninjured cohort.
This increase was found for those who had sustained burns during childhood (<15
years: IRR, 95% CI: 1.97, 1.49 to 2.61) and early to mid-adulthood (15-45 years:
IRR, 95% CI: 2.70, 2.06 to 3.55) and older adults (>=45 years: IRR, 95% CI: 1.62,
1.33 to 1.97). Significantly elevated first-time postburn admissions were
observed for children for 15 years postburn discharge (0-5 years: HR, 95% CI:
1.97, 1.75 to 2.22; 5-15 years: HR, 95% CI: 1.44, 1.28 to 1.63) and for adults 45
years and older at index burn for 5 years postburn only (HR, 95% CI: 1.72, 1.42
to 2.09). CONCLUSIONS: Burn injury appears to be associated with increased
nervous system-related morbidity for many years after burn injury. Further work
into the mechanisms and possible treatments to reduce this morbidity are
warranted in light of these findings.
PMID- 27609858
TI - Shaping dental contract reform: a clinical and cost-effective analysis of
incentive-driven commissioning for improved oral health in primary dental care.
AB - OBJECTIVE: To evaluate the clinical and cost-effectiveness of a new blended
dental contract incentivising improved oral health compared with a traditional
dental contract based on units of dental activity (UDAs). DESIGN: Non-randomised
controlled study. SETTING: Six UK primary care dental practices, three working
under a new blended dental contract; three matched practices under a traditional
contract. PARTICIPANTS: 550 new adult patients. INTERVENTIONS: A new
blended/incentive-driven primary care dentistry contract and service delivery
model versus the traditional contract based on UDAs. MAIN OUTCOME MEASURES:
Primary outcome was as follows: percentage of sites with gingival bleeding on
probing. Secondary outcomes were as follows: extracted and filled teeth (%),
caries (International Caries Detection and Assessment System (ICDAS)), oral
health-related quality of life (Oral Health Impact Profile-14 (OHIP-14)).
Incremental cost-effective ratios used OHIP-14 and quality adjusted life years
(QALYs) derived from the EQ-5D-3L. RESULTS: At 24 months, 291/550 (53%) patients
returned for final assessment; those lost to follow-up attended 6.46 appointments
on average (SD 4.80). The primary outcome favoured patients in the blended
contract group. Extractions and fillings were more frequent in this group.
Blended contracts were financially attractive for the dental provider but carried
a higher cost for the service commissioner. Differences in generic health-related
quality of life were negligible. Positive changes over time in oral health
related quality of life in both groups were statistically significant.
CONCLUSIONS: This is the first UK study to assess the clinical and cost
effectiveness of a blended contract in primary care dentistry. Although the
primary outcome favoured the blended contract, the results are limited because
47% patients did not attend at 24 months. This is consistent with 39% of adults
not being regular attenders and 27% only visiting their dentist when they have a
problem. Promotion of appropriate attendance, especially among those with high
need, necessitates being factored into recruitment strategies of future studies.
PMID- 27609860
TI - Optimization of Light-Harvesting Pigment Improves Photosynthetic Efficiency.
AB - Maximizing light capture by light-harvesting pigment optimization represents an
attractive but challenging strategy to improve photosynthetic efficiency. Here,
we report that loss of a previously uncharacterized gene, HIGH PHOTOSYNTHETIC
EFFICIENCY1 (HPE1), optimizes light-harvesting pigments, leading to improved
photosynthetic efficiency and biomass production. Arabidopsis (Arabidopsis
thaliana) hpe1 mutants show faster electron transport and increased contents of
carbohydrates. HPE1 encodes a chloroplast protein containing an RNA recognition
motif that directly associates with and regulates the splicing of target RNAs of
plastid genes. HPE1 also interacts with other plastid RNA-splicing factors,
including CAF1 and OTP51, which share common targets with HPE1. Deficiency of
HPE1 alters the expression of nucleus-encoded chlorophyll-related genes, probably
through plastid-to-nucleus signaling, causing decreased total content of
chlorophyll (a+b) in a limited range but increased chlorophyll a/b ratio.
Interestingly, this adjustment of light-harvesting pigment reduces antenna size,
improves light capture, decreases energy loss, mitigates photodamage, and
enhances photosynthetic quantum yield during photosynthesis. Our findings suggest
a novel strategy to optimize light-harvesting pigments that improves
photosynthetic efficiency and biomass production in higher plants.
PMID- 27609862
TI - Ebola and Zika: Cautionary tales.
PMID- 27609863
TI - News at a glance.
PMID- 27609859
TI - Multicentre, prospective, randomised, open-label, blinded end point trial of the
efficacy of allopurinol therapy in improving cardiovascular outcomes in patients
with ischaemic heart disease: protocol of the ALL-HEART study.
AB - INTRODUCTION: Ischaemic heart disease (IHD) is one of the most common causes of
death in the UK and treatment of patients with IHD costs the National Health
System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase
inhibitor used to prevent gout that also has several positive effects on the
cardiovascular system. The ALL-HEART study aims to determine whether allopurinol
improves cardiovascular outcomes in patients with IHD. METHODS AND ANALYSIS: The
ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label
blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no
treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and
over with IHD. Patients are followed up by electronic record linkage and annual
questionnaires for an average of 4 years. The primary outcome is the composite of
non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.
Secondary outcomes include all-cause mortality, quality of life and cost
effectiveness of allopurinol. The study will end when 631 adjudicated primary
outcomes have occurred. The study is powered at 80% to detect a 20% reduction in
the primary end point for the intervention. Patient recruitment to the ALL-HEART
study started in February 2014. ETHICS AND DISSEMINATION: The study received
ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2
(13/ES/0104). The study is event-driven and results are expected after 2019.
Results will be reported in peer-reviewed journals and at scientific meetings.
Results will also be disseminated to guideline committees, NHS organisations and
patient groups. TRIAL REGISTRATION NUMBER: 32017426, pre-results.
PMID- 27609864
TI - Campaign sets out to find a hot limit to life.
PMID- 27609865
TI - Cannonball! China's megasplash in ocean research.
PMID- 27609866
TI - The atmosphere's pacemaker skips a beat.
PMID- 27609867
TI - No proof that predator culls save livestock, study claims.
PMID- 27609868
TI - Accusations fly after big Gates grant.
PMID- 27609869
TI - Iranian sun.
PMID- 27609870
TI - A year after the deal, nuclear collaborations languish.
PMID- 27609861
TI - Rethinking Guard Cell Metabolism.
AB - Stomata control gaseous fluxes between the internal leaf air spaces and the
external atmosphere and, therefore, play a pivotal role in regulating CO2 uptake
for photosynthesis as well as water loss through transpiration. Guard cells,
which flank the stomata, undergo adjustments in volume, resulting in changes in
pore aperture. Stomatal opening is mediated by the complex regulation of ion
transport and solute biosynthesis. Ion transport is exceptionally well
understood, whereas our knowledge of guard cell metabolism remains limited,
despite several decades of research. In this review, we evaluate the current
literature on metabolism in guard cells, particularly the roles of starch,
sucrose, and malate. We explore the possible origins of sucrose, including guard
cell photosynthesis, and discuss new evidence that points to multiple processes
and plasticity in guard cell metabolism that enable these cells to function
effectively to maintain optimal stomatal aperture. We also discuss the new tools,
techniques, and approaches available for further exploring and potentially
manipulating guard cell metabolism to improve plant water use and productivity.
PMID- 27609871
TI - The reactor that triggered a nuclear crisis.
PMID- 27609872
TI - Zika vaccine trials.
PMID- 27609873
TI - Location, location, location.
PMID- 27609874
TI - Visualizing evolution as it happens.
PMID- 27609875
TI - Asymmetry in supramolecular assembly.
PMID- 27609876
TI - How dams can go with the flow.
PMID- 27609878
TI - Ahmed H. Zewail (1946-2016).
PMID- 27609877
TI - Lentiviral vectors, two decades later.
PMID- 27609879
TI - Donald A. Henderson (1928-2016).
PMID- 27609880
TI - Nuclear energy: Improve collaboration.
PMID- 27609881
TI - Cancel Yulin's annual dog meat festival.
PMID- 27609882
TI - Comment on "Principles of connectivity among morphologically defined cell types
in adult neocortex".
AB - Jiang et al (Research Article, 27 November 2015, aac9462) describe detailed
experiments that substantially add to the knowledge of cortical microcircuitry
and are unique in the number of connections reported and the quality of
interneuron reconstruction. The work appeals to experts and laypersons because of
the notion that it unveils new principles and provides a complete description of
cortical circuits. We provide a counterbalance to the authors' claims to give
those less familiar with the minutiae of cortical circuits a better sense of the
contributions and the limitations of this study.
PMID- 27609883
TI - Response to Comment on "Principles of connectivity among morphologically defined
cell types in adult neocortex".
AB - The critique of Barth et al centers on three points: (i) the completeness of our
study is overstated; (ii) the connectivity matrix we describe is biased by
technical limitations of our brain-slicing and multipatching methods; and (iii)
our cell classification scheme is arbitrary and we have simply renamed previously
identified interneuron types. We address these criticisms in our Response.
PMID- 27609884
TI - Biodiversity boundaries.
PMID- 27609885
TI - Synaptic mechanisms of pattern completion in the hippocampal CA3 network.
AB - The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3
CA3 synapses are thought to be the subcellular substrate of pattern completion.
However, the synaptic mechanisms of this network computation remain enigmatic. To
investigate these mechanisms, we combined functional connectivity analysis with
network modeling. Simultaneous recording from up to eight CA3 pyramidal neurons
revealed that connectivity was sparse, spatially uniform, and highly enriched in
disynaptic motifs (reciprocal, convergence, divergence, and chain motifs).
Unitary connections were composed of one or two synaptic contacts, suggesting
efficient use of postsynaptic space. Real-size modeling indicated that CA3
networks with sparse connectivity, disynaptic motifs, and single-contact
connections robustly generated pattern completion. Thus, macro- and
microconnectivity contribute to efficient memory storage and retrieval in
hippocampal networks.
PMID- 27609887
TI - Local near instantaneously dynamically triggered aftershocks of large
earthquakes.
AB - Aftershocks are often triggered by static- and/or dynamic-stress changes caused
by mainshocks. The relative importance of the two triggering mechanisms is
controversial at near-to-intermediate distances. We detected and located 48
previously unidentified large early aftershocks triggered by earthquakes with
magnitudes between >=7 and 8 within a few fault lengths (approximately 300
kilometers), during times that high-amplitude surface waves arrive from the
mainshock (less than 200 seconds). The observations indicate that near-to
intermediate-field dynamic triggering commonly exists and fundamentally promotes
aftershock occurrence. The mainshocks and their nearby early aftershocks are
located at major subduction zones and continental boundaries, and mainshocks with
all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger
early aftershocks.
PMID- 27609888
TI - Electromagnetic interference shielding with 2D transition metal carbides
(MXenes).
AB - Materials with good flexibility and high conductivity that can provide
electromagnetic interference (EMI) shielding with minimal thickness are highly
desirable, especially if they can be easily processed into films. Two-dimensional
metal carbides and nitrides, known as MXenes, combine metallic conductivity and
hydrophilic surfaces. Here, we demonstrate the potential of several MXenes and
their polymer composites for EMI shielding. A 45-micrometer-thick Ti3C2Tx film
exhibited EMI shielding effectiveness of 92 decibels (>50 decibels for a 2.5
micrometer film), which is the highest among synthetic materials of comparable
thickness produced to date. This performance originates from the excellent
electrical conductivity of Ti3C2Tx films (4600 Siemens per centimeter) and
multiple internal reflections from Ti3C2Tx flakes in free-standing films. The
mechanical flexibility and easy coating capability offered by MXenes and their
composites enable them to shield surfaces of any shape while providing high EMI
shielding efficiency.
PMID- 27609886
TI - Identification of an elaborate complex mediating postsynaptic inhibition.
AB - Inhibitory synapses dampen neuronal activity through postsynaptic
hyperpolarization. The composition of the inhibitory postsynapse and the
mechanistic basis of its regulation, however, remain poorly understood. We used
an in vivo chemico-genetic proximity-labeling approach to discover inhibitory
postsynaptic proteins. Quantitative mass spectrometry not only recapitulated
known inhibitory postsynaptic proteins but also revealed a large network of new
proteins, many of which are either implicated in neurodevelopmental disorders or
are of unknown function. Clustered regularly interspaced short palindromic
repeats (CRISPR) depletion of one of these previously uncharacterized proteins,
InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of
miniature inhibitory currents, and increased excitability in the hippocampus. Our
findings uncover a rich and functionally diverse assemblage of previously unknown
proteins that regulate postsynaptic inhibition and might contribute to
developmental brain disorders.
PMID- 27609889
TI - Highly siderophile elements were stripped from Earth's mantle by iron sulfide
segregation.
AB - Highly siderophile elements (HSEs) are strongly depleted in the bulk silicate
Earth (BSE) but are present in near-chondritic relative abundances. The
conventional explanation is that the HSEs were stripped from the mantle by the
segregation of metal during core formation but were added back in near-chondritic
proportions by late accretion, after core formation had ceased. Here we show that
metal-silicate equilibration and segregation during Earth's core formation
actually increased HSE mantle concentrations because HSE partition coefficients
are relatively low at the high pressures of core formation within Earth. The
pervasive exsolution and segregation of iron sulfide liquid from silicate liquid
(the "Hadean matte") stripped magma oceans of HSEs during cooling and
crystallization, before late accretion, and resulted in slightly suprachondritic
palladium/iridium and ruthenium/iridium ratios.
PMID- 27609890
TI - Dirhodium-catalyzed C-H arene amination using hydroxylamines.
AB - Primary and N-alkyl arylamine motifs are key functional groups in
pharmaceuticals, agrochemicals, and functional materials, as well as in bioactive
natural products. However, there is a dearth of generally applicable methods for
the direct replacement of aryl hydrogens with NH2/NH(alkyl) moieties. Here, we
present a mild dirhodium-catalyzed C-H amination for conversion of structurally
diverse monocyclic and fused aromatics to the corresponding primary and N-alkyl
arylamines using NH2/NH(alkyl)-O-(sulfonyl)hydroxylamines as aminating agents;
the relatively weak RSO2O-N bond functions as an internal oxidant. The
methodology is operationally simple, scalable, and fast at or below ambient
temperature, furnishing arylamines in moderate-to-good yields and with good
regioselectivity. It can be readily extended to the synthesis of fused N
heterocycles.
PMID- 27609892
TI - Digital discrimination: Political bias in Internet service provision across
ethnic groups.
AB - The global expansion of the Internet is frequently associated with increased
government transparency, political rights, and democracy. However, this
assumption depends on marginalized groups getting access in the first place. Here
we document a strong and persistent political bias in the allocation of Internet
coverage across ethnic groups worldwide. Using estimates of Internet penetration
obtained through network measurements, we show that politically excluded groups
suffer from significantly lower Internet penetration rates compared with those in
power, an effect that cannot be explained by economic or geographic factors. Our
findings underline one of the central impediments to "liberation technology,"
which is that governments still play a key role in the allocation of the Internet
and can, intentionally or not, sabotage its liberating effects.
PMID- 27609891
TI - Spatiotemporal microbial evolution on antibiotic landscapes.
AB - A key aspect of bacterial survival is the ability to evolve while migrating
across spatially varying environmental challenges. Laboratory experiments,
however, often study evolution in well-mixed systems. Here, we introduce an
experimental device, the microbial evolution and growth arena (MEGA)-plate, in
which bacteria spread and evolved on a large antibiotic landscape (120 * 60
centimeters) that allowed visual observation of mutation and selection in a
migrating bacterial front. While resistance increased consistently, multiple
coexisting lineages diversified both phenotypically and genotypically. Analyzing
mutants at and behind the propagating front, we found that evolution is not
always led by the most resistant mutants; highly resistant mutants may be trapped
behind more sensitive lineages. The MEGA-plate provides a versatile platform for
studying microbial adaption and directly visualizing evolutionary dynamics.
PMID- 27609893
TI - Optic flow odometry operates independently of stride integration in carried ants.
AB - Cataglyphis desert ants are impressive navigators. When the foragers roam the
desert, they employ path integration. For these ants, distance estimation is one
key challenge. Distance information was thought to be provided by optic flow (OF)
that is, image motion experienced during travel-but this idea was abandoned when
stride integration was discovered as an odometer mechanism in ants. We show that
ants transported by nest mates are capable of measuring travel distance
exclusively by the use of OF cues. Furthermore, we demonstrate that the
information gained from the optic flowmeter cannot be transferred to the stride
integrator. Our results suggest a dual information channel that allows the ants
to measure distances by strides and OF cues, although both systems operate
independently and in a redundant manner.
PMID- 27609894
TI - Collective cell durotaxis emerges from long-range intercellular force
transmission.
AB - The ability of cells to follow gradients of extracellular matrix stiffness
durotaxis-has been implicated in development, fibrosis, and cancer. Here, we
found multicellular clusters that exhibited durotaxis even if isolated
constituent cells did not. This emergent mode of directed collective cell
migration applied to a variety of epithelial cell types, required the action of
myosin motors, and originated from supracellular transmission of contractile
physical forces. To explain the observed phenomenology, we developed a
generalized clutch model in which local stick-slip dynamics of cell-matrix
adhesions was integrated to the tissue level through cell-cell junctions.
Collective durotaxis is far more efficient than single-cell durotaxis; it thus
emerges as a robust mechanism to direct cell migration during development, wound
healing, and collective cancer cell invasion.
PMID- 27609896
TI - Newton and the Big Apple.
PMID- 27609897
TI - Single-molecule dissection of stacking forces in DNA.
AB - We directly measured at the single-molecule level the forces and lifetimes of DNA
base-pair stacking interactions for all stack sequence combinations. Our
experimental approach combined dual-beam optical tweezers with DNA origami
components to allow positioning of blunt-end DNA helices so that the weak
stacking force could be isolated. Base-pair stack arrays that lacked a covalent
backbone connection spontaneously dissociated at average rates ranging from 0.02
to 500 per second, depending on the sequence combination and stack array size.
Forces in the range from 2 to 8 piconewtons that act along the helical direction
only mildly accelerated the stochastic unstacking process. The free-energy
increments per stack that we estimate from the measured forward and backward
kinetic rates ranged from -0.8 to -3.4 kilocalories per mole, depending on the
sequence combination. Our data contributes to understanding the mechanics of DNA
processing in biology, and it is helpful for designing the kinetics of DNA-based
nanoscale devices according to user specifications.
PMID- 27609895
TI - Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras
driven cancers.
AB - Tumor genetics guides patient selection for many new therapies, and cell culture
studies have demonstrated that specific mutations can promote metabolic
phenotypes. However, whether tissue context defines cancer dependence on specific
metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas
or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell
lung carcinoma (NSCLC), respectively, but despite the same initiating events,
these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors
incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source,
whereas PDAC tumors have decreased BCAA uptake. These differences are reflected
in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of
Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor
formation, but these enzymes are not required for PDAC tumor formation, arguing
that tissue of origin is an important determinant of how cancers satisfy their
metabolic requirements.
PMID- 27609899
TI - Social and economic impacts of climate.
AB - For centuries, thinkers have considered whether and how climatic conditions-such
as temperature, rainfall, and violent storms-influence the nature of societies
and the performance of economies. A multidisciplinary renaissance of quantitative
empirical research is illuminating important linkages in the coupled climate
human system. We highlight key methodological innovations and results describing
effects of climate on health, economics, conflict, migration, and demographics.
Because of persistent "adaptation gaps," current climate conditions continue to
play a substantial role in shaping modern society, and future climate changes
will likely have additional impact. For example, we compute that temperature
depresses current U.S. maize yields by ~48%, warming since 1980 elevated conflict
risk in Africa by ~11%, and future warming may slow global economic growth rates
by ~0.28 percentage points per year. In general, we estimate that the economic
and social burden of current climates tends to be comparable in magnitude to the
additional projected impact caused by future anthropogenic climate changes.
Overall, findings from this literature point to climate as an important influence
on the historical evolution of the global economy, they should inform how we
respond to modern climatic conditions, and they can guide how we predict the
consequences of future climate changes.
PMID- 27609898
TI - Improving the forecast for biodiversity under climate change.
AB - New biological models are incorporating the realistic processes underlying
biological responses to climate change and other human-caused disturbances.
However, these more realistic models require detailed information, which is
lacking for most species on Earth. Current monitoring efforts mainly document
changes in biodiversity, rather than collecting the mechanistic data needed to
predict future changes. We describe and prioritize the biological information
needed to inform more realistic projections of species' responses to climate
change. We also highlight how trait-based approaches and adaptive modeling can
leverage sparse data to make broader predictions. We outline a global effort to
collect the data necessary to better understand, anticipate, and reduce the
damaging effects of climate change on biodiversity.
PMID- 27609900
TI - Clinical Reasoning: Survey of Teaching Methods, Integration, and Assessment in
Entry-Level Physical Therapist Academic Education.
AB - Background: Although clinical reasoning abilities are important learning outcomes
of physical therapist entry-level education, best practice standards have not
been established to guide clinical reasoning curricular design and learning
assessment. Objective: This research explored how clinical reasoning is currently
defined, taught, and assessed in physical therapist entry-level education
programs. Design: A descriptive, cross-sectional survey was administered to
physical therapist program representatives. Methods: An electronic 24-question
survey was distributed to the directors of 207 programs accredited by the
Commission on Accreditation in Physical Therapy Education. Descriptive
statistical analysis and qualitative content analysis were performed. Post hoc
demographic and wave analyses revealed no evidence of nonresponse bias. Results:
A response rate of 46.4% (n=96) was achieved. All respondents reported that their
programs incorporated clinical reasoning into their curricula. Only 25% of
respondents reported a common definition of clinical reasoning in their programs.
Most respondents (90.6%) reported that clinical reasoning was explicit in their
curricula, and 94.8% indicated that multiple methods of curricular integration
were used. Instructor-designed materials were most commonly used to teach
clinical reasoning (83.3%). Assessment of clinical reasoning included practical
examinations (99%), clinical coursework (94.8%), written examinations (87.5%),
and written assignments (83.3%). Curricular integration of clinical reasoning
related self-reflection skills was reported by 91%. Limitations: A large number
of incomplete surveys affected the response rate, and the program directors to
whom the survey was sent may not have consulted the faculty members who were most
knowledgeable about clinical reasoning in their curricula. The survey
construction limited some responses and application of the results. Conclusions:
Although clinical reasoning was explicitly integrated into program curricula, it
was not consistently defined, taught, or assessed within or between the programs
surveyed-resulting in significant variability in clinical reasoning education.
These findings support the need for the development of best educational practices
for clinical reasoning curricula and learning assessment.
PMID- 27609901
TI - Development of an International Clinical Education Extracurricular Experience
Through a Collaborative Partnership.
AB - Background and Purpose: Participating in global health care through international
clinical education may enhance the development of cultural competence and
professionalism. Many logistical issues need to be resolved in the development of
international clinical education experiences that meet program requirements. The
purpose of this case report is to describe how a university developed such an
experience for students by partnering with Amizade Global Service-Learning
(Amizade), an organization that facilitates global learning experiences. Case
Description: Medical, nursing, and pharmacy students were already participating
in a 4-week international health-related service learning rotation through
Amizade. The preexisting relationship and contractual agreement with the
university provided the necessary legal framework. Amizade staff assisted in
finding a physical therapist qualified and willing to host a student. The
academic coordinator for clinical education at the university and Amizade
liaisons determined living arrangements, schedule, clinical settings, and patient
population. The selected student had expressed interest and had met all clinical
education placement requirements. The academic coordinator for clinical education
had ongoing electronic communications with all parties. Outcomes and Discussion:
The student demonstrated predicted attributes of cultural competence and
professionalism; through the partnership with Amizade, the student was exposed to
several unique interprofessional experiences. The steps used by the university
faculty in developing this interprofessional, international clinical education
experience through a collaborative partnership may provide guidance for other
institutions.
PMID- 27609903
TI - 'Face the facts: Stroke is treatable'.
PMID- 27609902
TI - TUT7 catalyzes the uridylation of the 3' end for rapid degradation of histone
mRNA.
AB - The replication-dependent histone mRNAs end in a stem-loop instead of the poly(A)
tail present at the 3' end of all other cellular mRNAs. Following processing, the
3' end of histone mRNAs is trimmed to 3 nucleotides (nt) after the stem-loop, and
this length is maintained by addition of nontemplated uridines if the mRNA is
further trimmed by 3'hExo. These mRNAs are tightly cell-cycle regulated, and a
critical regulatory step is rapid degradation of the histone mRNAs when DNA
replication is inhibited. An initial step in histone mRNA degradation is
digestion 2-4 nt into the stem by 3'hExo and uridylation of this intermediate.
The mRNA is then subsequently degraded by the exosome, with stalled intermediates
being uridylated. The enzyme(s) responsible for oligouridylation of histone mRNAs
have not been definitively identified. Using high-throughput sequencing of
histone mRNAs and degradation intermediates, we find that knockdown of TUT7
reduces both the uridylation at the 3' end as well as uridylation of the major
degradation intermediate in the stem. In contrast, knockdown of TUT4 did not
alter the uridylation pattern at the 3' end and had a small effect on uridylation
in the stem-loop during histone mRNA degradation. Knockdown of 3'hExo also
altered the uridylation of histone mRNAs, suggesting that TUT7 and 3'hExo
function together in trimming and uridylating histone mRNAs.
PMID- 27609904
TI - Differentiation of parathyroid carcinoma and adenoma by preoperative
ultrasonography.
AB - Background Parathyroid carcinomas (PTC) are very rare. There have been a few
studies on the contribution of ultrasound (US) in the diagnosis of PTC compared
with parathyroid adenomas (PTA). Purpose To identify the differences between US
findings of PTC and PTA in patients with primary hyperparathyroidism (PHPT).
Material and Methods We enrolled seven patients with PTC and 32 consecutive
patients with PTA whose diagnoses were confirmed by surgery at our institution
between March 1994 and June 2015. We retrospectively compared the US features of
the two groups, as well as the demographic, clinical, and biochemical
characteristics (age, gender, palpability, and serum ionized calcium and
parathyroid hormone [PTH] levels). Results The patients with PTC and PTA did not
exhibit significant differences in terms of mean age (59.0 years versus 51.1
years; P = 0.2063), sex distribution (male:female, 4:3 versus 1:3; P = 0.1716),
mean PTH levels (2855.0 pg/mL versus 1821.5 pg/mL; P = 0.2067), and mean ionized
calcium levels (1.7 mMol/L versus 1.5 mMol/L; P = 0.1585) except palpability ( P
< 0.0001). On US images, the PTCs were significantly larger (3.5 cm versus 1.9
cm; P = 0.0133) and exhibited higher incidences of heterogeneous echotexture ( P
= 0.0002), irregular shape ( P < 0.0001), non-circumscribed margin ( P < 0.0001),
intra-nodular calcifications ( P = 0.014), and local invasion ( P = 0.0004)
compared to the PTAs. Conclusion In preoperative patients with PHPT, PTCs are
differentiated from PTAs by their palpability and significant US features: large
size, heterogeneous echotexture, irregular shape, non-circumscribed margin, intra
nodular calcifications, and local invasion.
PMID- 27609905
TI - Justification and active guideline implementation for spine radiography referrals
in primary care.
AB - Background Spinal disorders are a major public health problem. Appropriate
diagnostic imaging is an essential part in the management of back complaints.
Nevertheless, inappropriate imaging increases population collective dose and
health costs without improving outcome. Purpose To determine the effects of
active implementation of referral guidelines on the number and justification of
spine radiography in primary care in one city. Material and Methods Specified
guidelines for spine radiography were distributed to referring practitioners
altogether three times during the study period. Educational lectures were
provided before the guidelines were taken into use. The guidelines were also made
available via the intranet. The number of spine radiography referrals during
similar 6-month periods in the year preceding the interventions and the following
2 years was analyzed. Justification of 448 spine radiographs was assessed
similarly. Results After interventions, the total number of spine radiography
examinations decreased by 48% (P < 0.001) and that of cervical spine radiography
by 46% ( P < 0.001), thoracic spine by 53% ( P < 0.001), and lumbar spine by 47%
( P < 0.001). The results persisted after 1-year follow-up. Before interventions,
24% of the cervical, 46% of the thoracic, and 32% of the lumbar spine radiography
referrals were justified. After interventions, only justification of lumbar spine
radiography improved significantly, 64% being justified ( P = 0.005). Conclusion
Spine radiography in primary care can be reduced significantly by active referral
guideline implementation. The proportion of inappropriate radiography was
unexpectedly high. Thus, further education and studies concerning the appropriate
use of spinal radiography seems to be needed.
PMID- 27609906
TI - Are the increasing amounts of gadolinium in surface and tap water dangerous?
PMID- 27609907
TI - Does the Company of a Dog Influence Affective Response to Exercise? Using
Ecological Momentary Assessment to Study Dog-Accompanied Physical Activity.
AB - PURPOSE: This study used ecological momentary assessment (EMA), a real-time self
report strategy, to examine (1) whether dog owners were more likely to be
physically active when they were with their dogs and (2) whether being with a dog
amplifies positive and dampens negative affective response during physical
activity. DESIGN: Electronic EMA surveys for 12 days. SETTING: Free-living.
PARTICIPANTS: Seventy-one adult dog owners. MEASURES: The EMA survey included 1
question about current activity, 3 questions about positive affect (Cronbach
alpha = .837), 4 questions about negative affect (Cronbach alpha = .865), and 1
question about the presence of dog. ANALYSIS: Multilevel modeling. RESULTS: The
company of a dog did not increase the likelihood of being active versus sedentary
at any given EMA prompt. However, greater positive affect during physical
activity was reported in the company of a dog. Negative affect did not differ
between active and sedentary activity, regardless of being with a dog or not.
CONCLUSION: This study demonstrates the utility of electronic EMA as a promising
methodology to study dog-accompanied physical activity. Future studies may use
EMA to collect further contextual information about dog-accompanied activity to
inform the development of innovative physical activity interventions.
PMID- 27609908
TI - Dietary Behavior and Predicted 10-Year Risk for a First Atherosclerotic
Cardiovascular Disease Event Using the Pooled Cohort Risk Equations Among US
Adults.
AB - PURPOSE: The pooled cohort equations were developed in 2013 by the American
College of Cardiology/American Heart Association Task Force to predict an
individual's 10-year risk of an atherosclerotic cardiovascular disease (ASCVD)
event. The purpose of the present study was to evaluate how predicted 10-year
ASCVD event risk varies as a function of daily dietary behavior. DESIGN: Cross
sectional. SETTING: National Health and Nutrition Examination Survey 2003 to
2006. PARTICIPANTS: A total of 2362 adults aged 40 to 79 years. MEASURES: The
ASCVD was assessed via the pooled cohort equations, with the Healthy Eating Index
calculated from self-reported dietary behavior. ANALYSIS: Multivariable linear
and logistic regression. RESULTS: Adults in the United States consuming a healthy
diet (vs those not consuming a healthy diet) had an 88% increased odds of being
at low risk for a future ASCVD event within the next 10 years (odds ratio [OR] =
1.88; 95% confidence interval [CI]: 1.35-2.68; P < .001). Similarly, those eating
a healthy diet had a 44% reduced odds of being at high risk for a future ASCVD
event within the next 10 years (OR = 0.56; 95% CI: 0.34-0.93; P = .02).
CONCLUSION: Among adults who were free of cardiovascular disease, those with a
healthy diet had reduced odds of being at high risk for a 10-year ASCVD event.
PMID- 27609909
TI - Promotion of Weight Loss by Health-Care Professionals: Implications for
Influencing Weight Loss/Control Behaviors.
AB - PURPOSE: Despite evidence demonstrating that health-care providers (HCPs) can
effectively promote health behaviors and weight loss among their patients, the
extent to which HCPs promote weight loss among overweight and obese adults is not
fully understood as the studies on this topic have mostly been conducted in
convenience samples. Therefore, the purpose of this study was to examine the
extent to which HCPs promote weight loss among overweight and obese adults.
DESIGN: Cross-sectional. SETTING: National Health and Nutrition Examination
Survey 2011-2012. PARTICIPANTS: A total of 2291 overweight or obese adults (males
46%, females 54%) of varying racial/ethnic backgrounds. MEASURES: Weight
loss/maintenance promotion from HCP was assessed via patient self-report, with
weight status assessed via measured body mass index. ANALYSIS: Descriptive
statistics and regression. RESULTS: Among those receiving health care in the past
12 months, 19.4% of overweight, 46.8% of obese class 1, 62.8% of obese class 2,
and 76.9% of obese class 3 adults were advised to lose/control their weight, and
the odds of being advised to control/lose weight by HCP increased accordingly.
These results were similar when evaluated across various subpopulations (eg, age,
gender). Those who received advice to lose/control weight had 3 times the odds of
adopting weight loss/control behaviors (odds ratio = 3.1). CONCLUSIONS:
Additional weight loss promotion among overweight and all classes of obese adults
is needed from HCP.
PMID- 27609910
TI - Complete Genome Sequence of Kosakonia sacchari Strain BO-1, an Endophytic
Diazotroph Isolated from a Sweet Potato.
AB - The complete genome sequence of the endophytic diazotroph Kosakonia sacchari,
isolated from a sweet potato, was analyzed. The 4,902,106-bp genome with 53.7%
G+C content comprises 4,638 open reading frames, including nif genes, 84 tRNAs,
and seven complete rRNAs in a circular chromosome.
PMID- 27609911
TI - Complete Genome Sequence of a GII.17 Norovirus Isolated from a Rhesus Monkey in
China.
AB - The previously silent GII.17 norovirus was found to be the predominant genotype
causing major epidemics in China in the 2014-2015 winter epidemic season. We
report here the complete genomic sequence of a GII.17 norovirus
(mky/GII.17/KM1509/CHN/2015) that infected rhesus monkeys at a monkey farm in
southwestern China.
PMID- 27609912
TI - Complete Genome Sequence of Clostridium septicum Strain CSUR P1044, Isolated from
the Human Gut Microbiota.
AB - Clostridium septicum is one of the first pathogenic anaerobes to be identified.
Here, we announce the genome draft sequence of C. septicum strain CSUR P1044
isolated from the gut of a healthy adult. Its chromosome genome consists of 3.2
Mbp with a plasmid of 32 Kbp. C. septicum strain CSUR P1044 has a G+C content of
27.5%, and is composed of 3,125 protein-coding genes together with 103 RNA genes,
including 22 rRNA genes.
PMID- 27609913
TI - Complete Genome Sequence of Two Rift Valley Fever Virus Strains Isolated from
Outbreaks in Saudi Arabia (2000) and Kenya (2006 to 2007).
AB - The complete genome sequence, including the untranslated regions, of two Rift
Valley fever virus (RVFV) strains isolated from mosquitoes that were collected
from disease outbreaks in Saudi Arabia (2001) and Kenya (2006 to 2007) were
sequenced using next-generation sequencing technology.
PMID- 27609914
TI - Complete Genome Sequence of the Pokeweed Mosaic Virus (PkMV)-New Jersey Isolate
and Its Comparison to PkMV-MD and PkMV-PA.
AB - Pokeweed mosaic virus (PkMV) causes systemically mosaic symptoms on pokeweed
(Phytolacca americana L.) plants. The genome of the PkMV-NJ (New Jersey) isolate
was cloned by PCR and sequenced by the Sanger sequencing method. The sequence
comparison indicates that PkMV-NJ is more divergent from the other two sequenced
isolates, PkMV-MD and PkMV-PA.
PMID- 27609915
TI - Draft Genome Sequence of Helicobacter suis Strain SNTW101, Isolated from a
Japanese Patient with Nodular Gastritis.
AB - We present here the draft whole-genome shotgun sequence of an uncultivated strain
SNTW101 of Helicobacter suis, which has been maintained in the stomachs of mice.
This strain was originally isolated from gastric biopsy specimens of a urea
breath test-negative Japanese patient suffering from nodular gastritis.
PMID- 27609916
TI - Draft Genome Sequences of 15 Isolates of Listeria monocytogenes Serotype 1/2a,
Subgroup ST204.
AB - Listeria monocytogenes sequence type 204 (ST204) strains have been isolated from
a range of food, environmental, and clinical sources in Australia. This study
describes the draft genome sequences of 15 isolates collected from meat and dairy
associated sources.
PMID- 27609917
TI - Draft Genome Sequences of Three Northern German Epidemic Staphylococcus aureus
(ST247) Strains Containing Multiple Copies of IS256.
AB - We report the draft genome sequences of three multiresistant Staphylococcus
aureus strains of sequence type 247 (ST247). The methicillin-resistant S. aureus
(MRSA) SA1450/94 is vancomycin susceptible, while the clinical MRSA isolate S.
aureus SA137/93A and its spontaneous laboratory mutant SA137/93G are
characterized by intermediate vancomycin susceptibility.
PMID- 27609918
TI - Genome Sequence of Marinobacter sp. Strain MCTG268 Isolated from the Cosmopolitan
Marine Diatom Skeletonema costatum.
AB - Marinobacter sp. strain MCTG268 was isolated from the cosmopolitan marine diatom
Skeletonema costatum and can degrade oil hydrocarbons as sole sources of carbon
and energy. Here, we present the genome sequence of this strain, which is
4,449,396 bp with 4,157 genes and an average G+C content of 57.0%.
PMID- 27609919
TI - Draft Genome Sequence of Tepidimonas taiwanensis Strain VT154-175.
AB - The slightly thermophilic bacterium Tepidimonas taiwanensis strain VT154-175 has
been isolated from a hot spring in the area of Viterbo, Italy. The whole draft
genome of 2.9 Mb obtained by paired-end next-generation sequencing and divided
into 60 scaffolds is presented.
PMID- 27609920
TI - Draft Genome Sequence of Uropathogenic Escherichia coli Strain NB8.
AB - Escherichia coli NB8 is a clinical pyelonephritis isolate. Here, we report the
draft genome sequence of uropathogenic E. coli NB8, which contains drug
resistance genes encoding resistance to beta-lactams, aminoglycosides,
quinolones, macrolides, colistin, sulfonamide-trimethoprim, and tetracycline. NB8
infects the kidney and bladder, making it an important tool for studying E. coli
pathogenesis.
PMID- 27609921
TI - Complete Genome Sequence of the Largest Known Flavi-Like Virus, Diaphorina citri
flavi-like virus, a Novel Virus of the Asian Citrus Psyllid, Diaphorina citri.
AB - A novel flavi-like virus tentatively named Diaphorina citri flavi-like virus
(DcFLV) was identified in field populations of Diaphorina citri through small RNA
and transcriptome sequencing followed by reverse transcription (RT)-PCR. We
report here the complete nucleotide sequence and genome organization of DcFLV,
the largest flavi-like virus identified to date.
PMID- 27609922
TI - Complete Genome Sequence of the Attenuated Corynebacterium pseudotuberculosis
Strain T1.
AB - We present here the genome sequence of the attenuated Corynebacterium
pseudotuberculosis strain T1. The sequencing was performed with an Ion Torrent
Personal Genome Machine platform. The genome is a circular chromosome of
2,337,201 bp, with a G+C content of 52.85% and a total of 2,125 coding sequences
(CDSs), 12 rRNAs, 49 tRNAs, and 24 pseudogenes.
PMID- 27609923
TI - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Blockley
Strain CRJJGF_00147 (Phylum Gammaproteobacteria).
AB - Here, we report a 4.72-Mbp draft genome sequence of Salmonella enterica subsp.
enterica serovar Blockley strain CRJJGF_00147, isolated from chicken rinse in
2009.
PMID- 27609924
TI - Draft Genome Sequence of Leptospira interrogans Serovar Bataviae Strain LepIMR 22
Isolated from a Rodent in Johor, Malaysia.
AB - Leptospira interrogans serovar Bataviae was recently identified as one of the
persistent Leptospira serovars in Malaysia. Here, we report the draft genome
sequence of the L. interrogans serovar Bataviae strain LepIMR 22 isolated from
kidney of a rodent in Johor, Malaysia.
PMID- 27609925
TI - Deep Sequencing Reveals the Complete Genome Sequence of Sweet potato virus G from
East Timor.
AB - We present the first complete Sweet potato virus G (SPVG) genome from sweet
potato in East Timor and compare it with seven complete SPVG genomes from South
Korea (three), Taiwan (two), Argentina (one), and the United States (one). It
most resembles the genomes from the United States and South Korea.
PMID- 27609926
TI - Complete Genome Sequence of a South Korean Isolate of Habenaria mosaic virus.
AB - Habenaria mosaic virus (HaMV), a member of the genus Potyvirus in the family
Potyviridae, was first discovered from Habenaria radiata in Japan. The complete
genomic sequence of a South Korean isolate (PA1) of HaMV infecting Plantago
asiatica L. was determined with high-throughput RNA sequencing.
PMID- 27609927
TI - Draft Genome Sequence of the Xanthomonas bromi Type Strain LMG 947.
AB - Here, we report the draft genome sequence of the Xanthomonas bromi type strain
LMG 947, an important pathogen of bromegrasses (Bromus spp.). Comparative
analysis with other Xanthomonas spp. that are pathogenic on forage grasses will
assist the analysis of host-plant adaptation at the genome level.
PMID- 27609928
TI - Genome Sequence of a Clinical Strain of Acinetobacter baumannii Belonging to the
ST79/PFGE-HUI-1 Clone Lacking the AdeABC (Resistance-Nodulation-Cell Division
Type) Efflux Pump.
AB - Increased expression of chromosomal genes for resistance-nodulation-cell division
type efflux systems plays a major role in the multidrug resistance of
Acinetobacter baumannii Little is known about the genetic characteristics of
clinical strains of Acinetobacter baumannii lacking the AdeABC pump. In this
study, we sequenced the genome of clinical strain Ab421 GEIH-2010 (belonging to
clone ST79/PFGE-HUI-1 from the GEIH-REIPI Ab. 2010 project) which lacks this
efflux pump.
PMID- 27609929
TI - Complete Genome Sequences of Neisseria gonorrhoeae with Coresistance to First
Line Antimicrobials.
AB - Neisseria gonorrhoeae strains with coresistance to the first-line antimicrobial
treatments azithromycin and ceftriaxone are an emerging public health threat.
Here, we present the complete genome sequences of three strains of N.
gonorrhoeae, including one susceptible strain and two strains with coresistance
to ceftriaxone and azithromycin.
PMID- 27609930
TI - Draft Genome Sequence of Ensifer adhaerens M78, a Mineral-Weathering Bacterium
Isolated from Soil.
AB - Ensifer adhaerens M78, a bacterium isolated from soil, can weather potash
feldspar and release Fe, Si, and Al from rock under nutrient-poor conditions.
Here, we report the draft genome sequence of strain M78, which may facilitate a
better understanding of the molecular mechanism involved in mineral weathering by
the bacterium.
PMID- 27609931
TI - Draft Genome Sequence of Two Strains of Xanthomonas arboricola Isolated from
Prunus persica Which Are Dissimilar to Strains That Cause Bacterial Spot Disease
on Prunus spp.
AB - The draft genome sequences of two strains of Xanthomonas arboricola, isolated
from asymptomatic peach trees in Spain, are reported here. These strains are
avirulent and do not belong to the same phylogroup as X. arboricola pv. pruni, a
causal agent of bacterial spot disease of stone fruits and almonds.
PMID- 27609932
TI - Pilot Testing of the EIT-4-BPSD Intervention.
AB - Behavioral and psychological symptoms of dementia are common in nursing home
residents, and the Centers for Medicare and Medicaid Services now require that
nonpharmacological interventions be used as a first-line treatment. Few staff
know how to implement these interventions. The purpose of this study was to pilot
test an implementation strategy, Evidence Integration Triangle for Behavioral and
Psychological Symptoms of Dementia (EIT-4-BPSD), which was developed to help
staff integrate behavioral interventions into routine care. The EIT-4-BPSD was
implemented in 2 nursing homes, and 21 residents were recruited. A research nurse
facilitator worked with facility champions and a stakeholder team to implement
the 4 steps of EIT-4-BPSD. There was evidence of reach to all staff;
effectiveness with improvement in residents' quality of life and a decrease in
agitation; adoption based on the environment, policy, and care plan changes; and
implementation and plans for maintenance beyond the 6-month intervention period.
PMID- 27609933
TI - Corrigendum.
AB - Toye, C., Lester, L., Popescu, A., McInerney, F., Andrews, S., & Robinson, A. L.
(2014). Dementia Knowledge Assessment Tool: Development and preliminary testing
with aged care staff and family carers. Dementia: The International Journal of
Social Research and Practice, 13, 248-256. DOI: 10.1177/1471301212471960The
wording are:"In Table 2, the item 'Knowing likely cause helps to predict' is
presented under the heading 'Incorrect statements' when it should be shown under
the heading 'Correct statements'".
PMID- 27609934
TI - Corrigendum.
AB - Article: Petrescu, I., MacFarlane, K. and Ranzijn, R. (2014) Psychological
effects of poetry workshops with people with early stage dementia: An exploratory
study. Dementia, 13(2), 207-215Following a dialogue with the authors, and to
clarify any misunderstanding, it should be noted that: 1) quoted poems in this
article belong to workshop participants, and 2) the in-text citation of the poems
by people with dementia as workshop participants should have said (quoted in
Petrescu & McNab, 2010 [page number citation as originally shared]).
PMID- 27609936
TI - Ultrasound-Assisted Catheter-Directed Thrombolysis: A Novel and Promising
Endovascular Therapeutic Modality for Intermediate-Risk Pulmonary Embolism.
AB - Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in
a substantial group of patients and carries a significant mortality risk. With
adequate risk stratification, catheter-directed techniques could be used as a
therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter
directed thrombolysis (UCDT) represents a novel endovascular technique with good
clinical and safety outcomes. Ultrasound-assisted catheter-directed thrombolysis
can achieve reduction in the thrombus burden and improvement of pulmonary
hemodynamics and right ventricular (RV) dysfunction and/or dilatation, without
major procedure-related complications, major bleeding, or hemorrhagic strokes.
This narrative review will focus on the major studies involving the efficacy and
safety of UCDT in the intermediate-risk PE population. Prospective, randomized
clinical trials with long-term follow-up and a large sample size are needed for
further evaluation of mortality benefit and to further define which subgroup of
patients may benefit from this novel endovascular technique.
PMID- 27609937
TI - An exploration of the impact of younger-onset dementia on employment.
AB - This study explored the emergence of dementia in people who were still working. A
qualitative life course approach was used to describe the experience from the
onset of dementia-related symptoms to the time when the person left the
workforce. The emergence of dementia at work for the participants in this study
took the form of a slow transition that initially was not noticed by co-workers.
It brought about subtle changes as the person became forgetful, disorganised,
made mistakes and was slower. Over time the person's job performance continued to
deteriorate and others at the workplace started to realise that there was a
problem. Some were seen to be poor workers and so experienced difficulties with
supervisors and co-workers. Others encountered difficulties managing changing
relationships at work and negotiating the complex world of the workplace. Few
were able to continue working beyond their diagnosis, and several raised concerns
about the lack of opportunities for people who develop dementia while still
employed. Given the greater participation of older people in the workforce,
findings highlight the importance of identifying and supporting workers with
declining cognitive function.
PMID- 27609938
TI - Improving safety for women in psychiatry wards.
PMID- 27609935
TI - What Signatures Dominantly Associate with Gene Age?
AB - As genes originate at different evolutionary times, they harbor distinctive
genomic signatures of evolutionary ages. Although previous studies have
investigated different gene age-related signatures, what signatures dominantly
associate with gene age remains unresolved. Here we address this question via a
combined approach of comprehensive assignment of gene ages, gene family
identification, and multivariate analyses. We first provide a comprehensive and
improved gene age assignment by combining homolog clustering with phylogeny
inference and categorize human genes into 26 age classes spanning the whole tree
of life. We then explore the dominant age-related signatures based on a
collection of 10 potential signatures (including gene composition, gene length,
selection pressure, expression level, connectivity in protein-protein interaction
network and DNA methylation). Our results show that GC content and connectivity
in protein-protein interaction network (PPIN) associate dominantly with gene age.
Furthermore, we investigate the heterogeneity of dominant signatures in
duplicates and singletons. We find that GC content is a consistent primary factor
of gene age in duplicates and singletons, whereas PPIN is more strongly
associated with gene age in singletons than in duplicates. Taken together, GC
content and PPIN are two dominant signatures in close association with gene age,
exhibiting heterogeneity in duplicates and singletons and presumably reflecting
complex differential interplays between natural selection and mutation.
PMID- 27609939
TI - Pharmacogenomics in psychiatry - Clinical innovation utilised by the Therapeutic
Goods Administration and Food and Drug Administration.
PMID- 27609940
TI - The Royal Australian and New Zealand College of Psychiatrists guidelines: Acute
inpatient care for schizophrenia.
PMID- 27609941
TI - Intravenous Acetaminophen for Postoperative Pain Management in Patients
Undergoing Living Laparoscopic Living-Donor Nephrectomy.
AB - BACKGROUND: Postoperative pain is a common complication of laparoscopic living
donor nephrectomies (LLDNs). OBJECTIVE: To determine whether intravenous (IV)
acetaminophen administration post-LLDN influenced length of stay (LOS) when used
for pain management. METHODS: This single-center, retrospective study compared
patients undergoing LLDN who had received IV acetaminophen for pain control
versus those who did not between June 1, 2011, and November 30, 2015. Patient
LOS, 30-day readmissions, frequency of pain assessments, patient-reported pain
scores, and opioid administration were assessed. RESULTS: A total of 90 patients
were included in the analysis (IV acetaminophen, n = 48; non-IV acetaminophen, n
= 42). Patients who did not receive IV acetaminophen were more often older (48.8
+/- 12.1 vs 39.3 +/- 12.1 years; P = 0.012) and female (71.4% vs 47.9%; P <
0.001). The average LOS was similar between the 2 groups (median = 3.0;
interquartile range = [3, 4] vs 3.5 [3, 4]; P = 0.737). The 30-day readmissions
were higher in the IV acetaminophen group (16.7%) compared with the group not
receiving IV acetaminophen (2.4%; P = 0.033). After the first postoperative day,
the frequencies of pain assessments performed were similar among the 2 groups.
There was no difference in average pain scores between the groups at any time
after LLDN. CONCLUSIONS: Patients receiving IV acetaminophen were found to have
no improvements in hospital LOS, average pain score, or opioid requirements
compared with patients not receiving IV acetaminophen. Patients who received IV
acetaminophen were also found to have a higher 30-day readmission rate.
PMID- 27609942
TI - Sofosbuvir/Velpatasvir: The First Pangenotypic Direct-Acting Antiviral
Combination for Hepatitis C.
AB - OBJECTIVES: To review the pharmacology, efficacy, and safety of
sofosbuvir/velpatasvir in the treatment of patients with hepatitis C virus (HCV)
infection. DATA SOURCES: A literature search through PubMed was conducted (June
2008 to August 2016) using the terms GS-5816, velpatasvir, and sofosbuvir.
References from retrieved articles and the prescribing information were reviewed
for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature
search was limited to human studies published in English. Phase I, II, and III
studies of sofosbuvir/velpatasvir for HCV were identified. DATA SYNTHESIS:
Sofosbuvir/velpatasvir is indicated for adult patients with chronic HCV genotype
1 through 6. It is given without ribavirin in patients with or without
compensated cirrhosis and with ribavirin in patients who have decompensated
cirrhosis. The ASTRAL-1 study demonstrated that sofosbuvir 400 mg plus
velpatasvir 100 mg for 12 weeks was effective at achieving high sustained
virological response (SVR12) rates in patients with HCV genotype 1, 2, 4, 5, or
6. The ASTRAL-2 and ASTRAL-3 studies demonstrated that the same regimen was
effective at achieving high SVR12 rates in patients with HCV genotype 2 or 3. The
ASTRAL-4 study demonstrated that the same regimen plus ribavirin was effective at
achieving high SVR12 rate in patients with decompensated cirrhosis. The most
common adverse reactions (>=10% of patients) associated with
sofosbuvir/velpatasvir were headache and fatigue. CONCLUSIONS:
Sofosbuvir/velpatasvir is safe and effective to treat HCV genotypes 1, 2, 3, 4,
5, and 6 in patients with or without compensated cirrhosis. The addition of
ribavirin is recommended in patients with decompensated cirrhosis.
PMID- 27609943
TI - Discovery of new biomarkers for atrial fibrillation using a custom-made
proteomics chip.
AB - BACKGROUND: Apart from several established clinical risk factors for atrial
fibrillation (AF), a number of biomarkers have also been identified as potential
risk factors for AF. None of these have so far been adopted in clinical practice.
OBJECTIVE: To use a novel custom-made proteomics chip to discover new prognostic
biomarkers for AF risk. METHODS: In two independent community-based cohorts
(Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
(978 participants without AF, mean age 70.1 years, 50% women, median follow-up
10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n=725, mean age
77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were
assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85
proteins showed a call rate >70% in both cohorts. RESULTS: Thirteen proteins were
related to incident AF in PIVUS (148 events) using a false discovery rate of 5%.
Of those, five were replicated in ULSAM at nominal multivariable p value (123
events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth
factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation
factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23
were also associated with AF after adjusting for established AF risk factors. In
a prespecified secondary analysis pooling the two data sets, T-cell
immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also
significantly related to incident AF in addition to the aforementioned five
proteins (Bonferroni-adjustment). The addition of NT-pro-BNP to a model with
established risk factors increased the C-statistic from 0.605 to 0.676
(p<0.0001). CONCLUSIONS: Using a novel proteomics approach, we confirmed the
previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident
AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be
of importance in the development of AF.
PMID- 27609944
TI - Pixels or Pixie Dust? Grading of mitral regurgitation using intensity analysis of
continuous wave Doppler.
PMID- 27609947
TI - CCTV uptake in abattoirs 'may have plateaued', says FSA.
PMID- 27609956
TI - Veterinary medicines update.
AB - The following information has been produced for Veterinary Record by the
Veterinary Medicines Directorate (VMD) to provide an update for veterinary
surgeons on recent changes to marketing authorisations for veterinary medicines
in the UK and on other relevant issues.
PMID- 27609945
TI - Opening Pandora's Box: A Chest Radiograph in a 5-Month-Old With Bronchiolitis.
PMID- 27609958
TI - Being a vet 'means much more than solely being a clinician'.
PMID- 27609959
TI - New RCVS President calls on vets and vet nurses to 'wear their badge with pride'.
PMID- 27609961
TI - RCVS honours and awards.
PMID- 27609962
TI - What is causing smothering in laying hens?
PMID- 27609963
TI - Should vets be concerned about biodiversity loss?
AB - Sean Wensley believes there are sound justifications for the profession to act.
PMID- 27609964
TI - Dearth of evidence for EBVM.
PMID- 27609965
TI - Tongue worm (Linguatula species) in stray dogs imported into the UK.
PMID- 27609966
TI - Survey on illegal dog fighting.
PMID- 27609967
TI - Urinary incontinence in dogs.
PMID- 27609975
TI - A vet with a vision.
AB - When he learned what being a veterinarian meant, Gil Ben-Shlomo felt that the
career had been invented especially for him. He has since specialised, and is now
professor of ophthalmology at Iowa State University.
PMID- 27609976
TI - Student diary (about to be a third-year).
AB - Having passed her exams, Rosie Perrett has done extramural studies at pig, dairy
and poultry units and a small animal practice. She is now relaxing before she
starts her third year at Liverpool.
PMID- 27609977
TI - Nephrolithiasis among male patients with newly diagnosed gout.
AB - INTRODUCTION: An elevated serum urate level is recognised as a cause of gouty
arthritis and uric acid stone. The level of serum uric acid that accelerates
kidney stone formation, however, has not yet been clarified. This study aimed to
find out if a high serum urate level is associated with nephrolithiasis. METHODS:
Patients were recruited from the rheumatology clinic of Taipei City Hospital
(Renai and Zhongxing branches) in Taiwan from March 2015 to February 2016. A
total of 120 Chinese male patients with newly diagnosed gout and serum urate
concentration of >7 mg/dL and no history of kidney stones were divided into two
groups according to their serum urate level: <10 mg/dL (group 1, n=80) and >=10
mg/dL (group 2, n=40). The mean body mass index, blood urea nitrogen level,
creatinine level, urinary pH, and kidney ultrasonography were compared between
the two groups. RESULTS: There were no significant differences in blood urea
nitrogen or creatinine level between the two groups. The urine pH in both groups
was similar and not statistically significant. Kidney stone formation was
detected via ultrasonography in 6.3% (5/80) and 82.5% (33/40) of patients in
groups 1 and 2, respectively (P<0.05). CONCLUSION: A serum urate level of >=10
mg/dL may precipitate nephrolithiasis. Further studies are warranted to
substantiate the relationship between serum urate level and kidney stone
formation.
PMID- 27609979
TI - Prevalence and patient characteristics of Mayer-Rokitansky-Kuster-Hauser
syndrome: a nationwide registry-based study.
AB - STUDY QUESTION: What is the prevalence of Mayer-Rokitansky-Kuster-Hauser (MRKH)
syndrome? SUMMARY ANSWER: The prevalence of MRKH syndrome in Denmark is 1 in 4982
(95% confidence interval (CI): 4216-5887) live female births. WHAT IS KNOWN
ALREADY: The prevalence of MRKH syndrome has been estimated to be around 1 in
4000-5000 females. However, population-based prevalence studies of MRKH syndrome
are sparse. Moreover, population-based data on patient characteristics are
lacking. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study used the
Danish National Patient Registry (DNPR) to identify a nationwide population-based
cohort of patients with MRKH syndrome. Subsequently, patients were linked to the
Danish Cytogenetic Central Registry (DCCR) and patient medical records in order
to validate the diagnoses. PARTICIPANTS/MATERIALS, SETTING, METHODS:
Hospitalizations and outpatient visits from 1994 to April 2015 at all public
hospitals in Denmark were searched for patients assigned with a diagnosis code
indicative of MRKH syndrome. The diagnoses were validated by diagnostic history
in the DNPR and DCCR data, and by review of patient medical records. The
prevalence was estimated considering the identified patients born from 1974 to
1996. Patient characteristics were described using data collected from DNPR, DCCR
and patient medical records. MAIN RESULTS AND THE ROLE OF CHANCE: The diagnosis
was validated in 304 of 314 patients (96.8%) suspected with MRKH syndrome by
review of diagnostic histories, DCCR data, and medical records and in 168
patients, the diagnosis of MRKH syndrome was confirmed (positive predictive value
= 55.3% (95% CI: 49.5-60.9%)). The prevalence was 1 in 4982 (95% CI: 4216-5887)
live female births based on 138 patients born from 1974 to 1996. Typical MRKH
syndrome and atypical MRKH syndrome/Mullerian duct aplasia, Renal aplasia, and
Cervicothoracic Somite dysplasia association were present in 56.5% and 43.5% of
the patients, respectively. Kidney malformations were the most prevalent
extragenital malformations, described in 38 of 111 patients (34.2%). However, in
57 patients (33.9%) no urinary tract imaging was performed. Three familial cases
of MRKH syndrome were identified. LIMITATIONS, REASONS FOR CAUTION: We identified
all patients with MRKH syndrome diagnosed at public hospitals in Denmark. When
interpreting the prevalence estimate, caution must be taken due to limitations
such as patients not diagnosed in public hospitals, other diagnosis codes not
used in the study and the unknown impact of a net positive migration rate in
Denmark. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence estimate around 1 in
5000 is in accordance with a previous nationwide study. We consider the
prevalence generalizable to other Caucasian populations. Prevalence studies of
non-Caucasian populations are needed to investigate whether inter-ethnic
differences in prevalence exist. Finally, the results of this study emphasize the
need for sufficient basic examinations of patients with MRKH syndrome, including
the importance of family medical history. STUDY FUNDING/COMPETING INTERESTS:
None.
PMID- 27609978
TI - Specific immune cell and cytokine characteristics of human testicular germ cell
neoplasia.
AB - STUDY QUESTION: Which immune cells and cytokine profiles are characteristic for
testicular germ cell neoplasia and what consequences does this have for the
understanding of the related testicular immunopathology? SUMMARY ANSWER: The
unique immune environment of testicular germ cell neoplasia comprises B cells and
dendritic cells as well as high transcript levels of IL-6 and other B cell
supporting or T helper cell type 1 (Th1)-driven cytokines and thus differs
profoundly from normal testis or inflammatory lesions associated with
hypospermatogenesis. WHAT IS KNOWN ALREADY: T cells are known to be the major
component of inflammatory infiltrates associated with either hypospermatogenesis
or testicular cancer. It has previously been reported that B cells are only
involved within infiltrates of seminoma samples, but this has not been
investigated further. STUDY DESIGN, SIZE, DURATION: Immunohistochemical
characterisation (IHC) of infiltrating immune cells and RT-qPCR-based analysis of
corresponding cytokine microenvironments was performed on different testicular
pathologies. Testicular biopsies, obtained from men undergoing andrological work
up of infertility or taken during surgery for testicular cancer, were used in
this study. Samples were grouped as follows: (i) normal spermatogenesis (n = 18),
(ii) hypospermatogenesis associated with lymphocytic infiltrates (n = 10), (iii)
samples showing neoplasia [germ cell neoplasia in situ (GCNIS, n = 26) and
seminoma, n = 18]. PARTICIPANTS/MATERIALS, SETTING, METHODS: IHC was performed
using antibodies against T cells (CD3+), B cells (CD20cy+), dendritic cells
(CD11c+), macrophages (CD68+) and mast cells (mast cell tryptase+). Degree and
compartmental localisation of immune cells throughout all groups analysed was
evaluated semi-quantitatively. RT-qPCR on RNA extracted from cryo-preserved
tissue samples was performed to analyse mRNA cytokine expression, specifically
levels of IL-1beta, IL-6, IL-17a, tumour necrosis factor (TNF)-alpha (pro
inflammatory), IL-10, transforming growth factor (TGF)-beta1 (anti-inflammatory),
IL-2, IL-12a, IL-12b, interferon (IFN)-gamma (Th1-driven), IL-4, IL-5, IL-13, IL
23a (Th2-driven), CXCL-13, CXCL-10 and CCL-5 (chemokines). MAIN RESULTS AND THE
ROLE OF CHANCE: This is the first study showing a direct linkage between the
distribution pattern of immune cells in hypospermatogenesis versus testicular
cancer and analysis of a wide range of 17 related cyto- and chemokines. A
fundamental difference between testicular inflammation patterns associated with
different testicular inflammatory conditions either containing or lacking
neoplastic cells was demonstrated. In hypospermatogenesis, T cells were detected,
whereas B cells and dendritic cells were almost absent. Within GCNIS and
seminoma, in addition to T cells, high numbers of dendritic cells and B cells
were found, the latter additionally organised in cell clusters, whereas mast
cells were absent. Transcripts encoding pro-inflammatory cytokines (IL-1beta, IL
6 and TNF-alpha), anti-inflammatory cytokines (TGF-beta1), Th1-driven cytokines
(IL-2 and IFN-gamma) as well as chemokines (CXCL-13, CXCL-10 and CCL-5) were all
significantly increased in testicular germ cell neoplasia (P <= 0.01), suggesting
the presence of a pro-tumorigenic environment. In contrast, Th2-related cytokines
(IL-5, IL-13 and IL-23a) characterised the environment within samples showing
normal spermatogenesis as well as hypospermatogenesis. One of the most important
outcomes is the pivotal role of IL-6 in testicular cancer that opens potential
novel diagnostic and/or immune-therapeutic perspective for testis cancer.
LIMITATIONS, REASONS FOR CAUTION: Testicular tissue composed of immune cells as
well as other somatic cells and germ cells does not allow identification of
specific cytokine sources or single cell types, being responsible for
establishing the overall cytokine environment. In this study, laser-assisted
microdissection did not reach the required efficiency for RT-qPCR analyses.
Therefore, in vitro models would be suggested for addressing the above-mentioned
issue. Conclusions about cytokine levels in testes with GCNIS are based on a
small number of samples. WIDER IMPLICATIONS OF THE FINDINGS: The unique B cell
presence and the significantly increased expression level of IL-6 in testicular
germ cell neoplasia (P < 0.001) strengthen its special role in this disease. In
line with current knowledge on other types of cancer, these results underline the
relevance of further investigating the potential of IL-6 as early biomarker and
target for therapeutic intervention in testicular germ cell neoplasia. STUDY
FUNDING/COMPETING INTERESTS: This study (and B.K. in person) was supported by the
Deutsche Forschungsgemeinschaft (DFG) as part of the International Research
Training Group between Justus Liebig University of Giessen and Monash University,
Melbourne (GRK 1871/1) on 'Molecular pathogenesis on male reproductive
disorders'. T.H., H.-C.S. and M.B. were supported by the LOEWE focus group
'MIBIE' (male infertility during infection & inflammation)-an excellence
initiative of the German state government of Hessen. From the Australian side,
K.L. was supported by NHMRC grants (Fellowship, ID1079646 and Project,
ID1081987); K.L., S.I. and M.H. received scholarship (S.I.) and research funding
(K.L., M.H.) from Monash University. The project also drew support from the
Victorian Government's Operational Infrastructure Support Program. The authors
have no competing interests to declare.
PMID- 27609980
TI - Development of a generally applicable morphokinetic algorithm capable of
predicting the implantation potential of embryos transferred on Day 3.
AB - STUDY QUESTION: Can a generally applicable morphokinetic algorithm suitable for
Day 3 transfers of time-lapse monitored embryos originating from different
culture conditions and fertilization methods be developed for the purpose of
supporting the embryologist's decision on which embryo to transfer back to the
patient in assisted reproduction? SUMMARY ANSWER: The algorithm presented here
can be used independently of culture conditions and fertilization method and
provides predictive power not surpassed by other published algorithms for ranking
embryos according to their blastocyst formation potential. WHAT IS KNOWN ALREADY:
Generally applicable algorithms have so far been developed only for predicting
blastocyst formation. A number of clinics have reported validated implantation
prediction algorithms, which have been developed based on clinic-specific culture
conditions and clinical environment. However, a generally applicable embryo
evaluation algorithm based on actual implantation outcome has not yet been
reported. STUDY DESIGN, SIZE, DURATION: Retrospective evaluation of data
extracted from a database of known implantation data (KID) originating from 3275
embryos transferred on Day 3 conducted in 24 clinics between 2009 and 2014. The
data represented different culture conditions (reduced and ambient oxygen with
various culture medium strategies) and fertilization methods (IVF, ICSI). The
capability to predict blastocyst formation was evaluated on an independent set of
morphokinetic data from 11 218 embryos which had been cultured to Day 5.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The algorithm was developed by applying
automated recursive partitioning to a large number of annotation types and
derived equations, progressing to a five-fold cross-validation test of the
complete data set and a validation test of different incubation conditions and
fertilization methods. The results were expressed as receiver operating
characteristics curves using the area under the curve (AUC) to establish the
predictive strength of the algorithm. MAIN RESULTS AND THE ROLE OF CHANCE: By
applying the here developed algorithm (KIDScore), which was based on six
annotations (the number of pronuclei equals 2 at the 1-cell stage, time from
insemination to pronuclei fading at the 1-cell stage, time from insemination to
the 2-cell stage, time from insemination to the 3-cell stage, time from
insemination to the 5-cell stage and time from insemination to the 8-cell stage)
and ranking the embryos in five groups, the implantation potential of the embryos
was predicted with an AUC of 0.650. On Day 3 the KIDScore algorithm was capable
of predicting blastocyst development with an AUC of 0.745 and blastocyst quality
with an AUC of 0.679. In a comparison of blastocyst prediction including six
other published algorithms and KIDScore, only KIDScore and one more algorithm
surpassed an algorithm constructed on conventional Alpha/ESHRE consensus timings
in terms of predictive power. LIMITATIONS, REASONS FOR CAUTION: Some
morphological assessments were not available and consequently three of the
algorithms in the comparison were not used in full and may therefore have been
put at a disadvantage. Algorithms based on implantation data from Day 3 embryo
transfers require adjustments to be capable of predicting the implantation
potential of Day 5 embryo transfers. The current study is restricted by its
retrospective nature and absence of live birth information. Prospective
Randomized Controlled Trials should be used in future studies to establish the
value of time-lapse technology and morphokinetic evaluation. WIDER IMPLICATIONS
OF THE FINDINGS: Algorithms applicable to different culture conditions can be
developed if based on large data sets of heterogeneous origin. STUDY
FUNDING/COMPETING INTERESTS: This study was funded by Vitrolife A/S, Denmark and
Vitrolife AB, Sweden. B.M.P.'s company BMP Analytics is performing consultancy
for Vitrolife A/S. M.B. is employed at Vitrolife A/S. M.M.'s company ilabcomm
GmbH received honorarium for consultancy from Vitrolife AB. D.K.G. received
research support from Vitrolife AB.
PMID- 27609981
TI - Prenatal paracetamol exposure is associated with shorter anogenital distance in
male infants.
AB - STUDY QUESTION: What is the relationship between maternal paracetamol intake
during the masculinisation programming window (MPW, 8-14 weeks of gestation) and
male infant anogenital distance (AGD), a biomarker for androgen action during the
MPW? SUMMARY ANSWER: Intrauterine paracetamol exposure during 8-14 weeks of
gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS
ALREADY KNOWN: The increasing prevalence of male reproductive disorders may
reflect environmental influences on foetal testicular development during the MPW.
Animal and human xenograft studies have demonstrated that paracetamol reduces
foetal testicular testosterone production, consistent with reported
epidemiological associations between prenatal paracetamol exposure and
cryptorchidism. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Cambridge
Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual
weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24
months of infant follow-up. Of 2229 recruited women, 1640 continued with the
infancy study after delivery, of whom 676 delivered male infants and completed a
medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD:
Mothers self-reported medicine consumption during pregnancy by a questionnaire
administered during the perinatal period. Infant AGD (measured from 2006
onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and
24 months of age, and age-specific Z scores were calculated. Associations between
paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14
weeks) and these outcomes were tested by linear mixed models. Two hundred and
twenty-five (33%) of six hundred and eighty-one male infants were exposed to
paracetamol during pregnancy, of whom sixty-eight were reported to be exposed
during 8-14 weeks. AGD measurements were available for 434 male infants. MAIN
RESULTS AND THE ROLE OF CHANCE: Paracetamol exposure during 8-14 weeks of
gestation, but not any other period, was associated with shorter AGD (by 0.27 SD,
95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was
independent of body size. Paracetamol exposure was not related to penile length
or testicular descent. LIMITATIONS, REASONS FOR CAUTION: Confounding by other
drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not
fully representative of pregnant women in the UK, particularly in terms of
maternal ethnicity and smoking prevalence. There is likely to have been
misclassification of paracetamol exposure due to recall error. WIDER IMPLICATIONS
OF THE FINDINGS: Our observational findings support experimental evidence that
intrauterine paracetamol exposure during the MPW may adversely affect male
reproductive development. STUDY FUNDING/COMPETING INTERESTS: This work was
supported by a European Union Framework V programme, the World Cancer Research
Fund International, the Medical Research Council (UK), the Newlife Foundation for
Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead
Johnson Nutrition, and the National Institute for Health Research Cambridge
Comprehensive Biomedical Research Centre. The authors declare no conflict of
interest.
PMID- 27609982
TI - Development of a new clinically applicable device for embryo evaluation which
measures embryo oxygen consumption.
AB - STUDY QUESTION: Does a new system-the chip-sensing embryo respiration monitoring
system (CERMs)-enable evaluation of embryo viability for potential application in
a clinical IVF setting? SUMMARY ANSWER: The system enabled the oxygen consumption
rate of spheroids, bovine embryos and frozen-thawed human embryos to be measured,
and this rate corresponded to the developmental potential of embryos. WHAT IS
ALREADY KNOWN: To date, no reliable and clinically suitable objective evaluation
methods for embryos are available, which circumvent the differences in inter
observer subjective view. Existing systems such as the scanning electrochemical
microscopy (SECM) technique, which enables the measurement of oxygen consumption
rate in embryos, need improvement in usability before they can be applied to a
clinical setting. STUDY DESIGN, SIZE, DURATION: This is a prospective original
research study. The feasibility of measuring the oxygen consumption rate was
assessed using CERMs for 9 spheroids, 9 bovine embryos and 30 redundant frozen
thawed human embryos. The endpoints for the study were whether CERMs could detect
a dissolved oxygen gradient with high sensitivity, had comparable accuracy to the
SECM measuring system with improved usability, and could predict the development
of an embryo to a blastocyst by measuring the oxygen consumption rate. The
relationship between the oxygen consumption rate and standard morphological
evaluation was also examined. PARTICIPANTS/MATERIALS, SETTING, METHODS: We
developed a new CERMs, which enables the oxygen consumption rate to be measured
automatically using an electrochemical method. The device was initially used for
measuring a dissolved oxygen concentration gradient in order to calculate oxygen
consumption rate using nine spheroids. Next, we evaluated data correlation
between the CERMs and the SECM measuring systems using nine bovine embryos.
Finally, the oxygen consumption rates of 30 human embryos, which were frozen
thawed on 2nd day after fertilization, were measured by CERMs at 6, 24, 48, 72
and 96 h after thawing with standard morphological evaluation. Furthermore, the
developed blastocysts were scored using the blastocyst quality score (BQS), and
the correlation with oxygen consumption rate was also assessed. MAIN RESULTS AND
THE ROLE OF CHANCE: The device enabled the oxygen consumption rate of an embryo
to be measured automatically within a minute. The oxygen concentration gradient
profile showed excellent linearity in a distance-dependent change. A close
correlation in the oxygen consumption rates of bovine embryos was observed
between the SECM measuring system and CERMs, with a determination coefficient of
0.8203 (P = 0.0008). Oxygen consumption rates of human embryos that have reached
the blastocyst stage were significantly higher than those of arrested embryos at
48, 72 and 96 h after thawing (P = 0.039, 0.004 and 0.049, respectively). Thus,
in vitro development of frozen-thawed human embryos to the blastocyst stage would
be predicted at 48 h after thawing (day 4) by measuring the oxygen consumption
using CERMs. Although a positive linear relationship between BQS and the oxygen
consumption rate was observed [the determination coefficient was R(2) = 0.6537 (P
= 0.008)], two blastocysts exhibited low oxygen consumption rates considering
their relatively high BQS. This suggests that morphology and metabolism in human
embryos might not correlate consistently. LIMITATIONS, REASONS FOR CAUTION:
Transfer of the embryo and pregnancy evaluation was not performed. Thus, a
correlation between oxygen consumption and the in vivo viability of embryos
remains unknown. Clinical trials, including embryo transfer, would be desirable
to determine a threshold value to elect clinically relevant, quality embryos for
transfer. We utilized frozen-thawed human embryos in this study. The effect of
these manipulations on the respiratory activity of the embryo is also unknown.
WIDER IMPLICATIONS OF THE FINDINGS: Selection of quality embryos, especially in a
single embryo transfer cycle, by CERMs may have an impact on obtaining better
clinical outcomes, albeit with clinical trials being required. Furthermore, the
early determination of quality embryos by CERMs may enable the omission of long
term in vitro embryo culture to the blastocyst stage. CERMs is scalable
technology that can be integrated into incubators and/or other embryo evaluation
systems, such as the time-lapse systems, due to its chip-based architecture.
Thus, CERMS would enable automatic measurement of oxygen consumption, under 5%
CO2, in the near future, in order to reduce oxidative stress from exposure to
atmospheric air. STUDY FUNDING/COMPETING INTERESTS: This study was supported by
grants from the Health and Labor Sciences Research Grant (H24-Hisaichiiki-Shitei
016). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Not
applicable.
PMID- 27609983
TI - Use of donor sperm in addition to oocyte donation after repeated implantation
failure in normozoospermic patients does not improve live birth rates.
AB - STUDY QUESTION: Does switching to donor semen after at least three failed oocyte
donation (OD) cycles with the partner normozoospermic semen increase the live
birth rate in a subsequent OD cycle? SUMMARY ANSWER: Switching to donor semen
after at least three failed OD cycles with the partner normozoospermic semen does
not increase the live birth rate. WHAT IS ALREADY KNOWN: In some patients, a
viable pregnancy cannot be achieved after several OD cycles, despite normal
diagnostic findings for the couple. The ESHRE Capri Workshop Group indicates
that, in order to improve reproductive outcomes, a semen donation can be offered
after three failed ICSI cycles. STUDY DESIGN, SIZE, DURATION: A retrospective
cohort analysis of fourth and fifth OD cycles with either the partner's
normozoospermic semen (OD) or double-donation cycles (DD), performed between
January 2011 and December 2014 in a private fertility center. These couples did
not have a known male factor. PARTICIPANTS/MATERIALS, SETTING, METHOD: The study
included 228 cycles (159 OD and 69 DD). The fertilization method was ICSI in all
cycles and embryos were transferred fresh. Fertilization rates were compared
between groups using ANOVA while pregnancy outcomes were compared using Chi
square tests. Effect of DD on pregnancy outcomes was further analyzed using a
logistic regression model adjusted for recipient's age and BMI, number of embryos
transferred, day of embryo transfer and morphological embryo quality score. MAIN
RESULTS AND THE ROLE OF CHANCE: There was no difference in live birth rate
between the DD and OD groups (38.2 versus 35.8%, P = 0.73), even after adjustment
for confounding factors (odds ratio 1.41, 95% confidence interval 0.72, 2.76; P =
0.31). Rates of biochemical pregnancy (52.2 versus 54.1%, P = 0.79), clinical
pregnancy (41.2 versus 45.9%, P = 0.51) and ongoing pregnancy (38.2 versus 37.1%,
P = 0.87) were not different between the DD and the OD groups, as well as
fertilization rate (75.3 versus 75.2%, P = 0.97). The DD and OD groups were
comparable at baseline in all demographic and cycle variables analyzed
(recipient's BMI, number of transferred embryos and embryo quality) with the
exception of recipient's age (42.3 in DD versus 44.1 in OD, P = 0.005), and day
of embryo transfer (56.5% of DD and 83.6% of OD embryo transfers were performed
on blastocyst stage, P < 0.001); both variables were adjusted for in the
multivariate analysis. LIMITATIONS, REASONS FOR CAUTION: The main limitations of
this study are its retrospective nature, the relatively small sample size, the
transfer of embryos of different developmental stages and the lack of extensive
molecular testing, such as sperm DNA fragmentation test, in normozoospermic
patients. WIDER IMPLICATIONS OF THE FINDINGS: After excluding several causes for
the failed OD cycles, the partner's normozoospermic semen was a common factor in
all of them. Nevertheless, the change to a donor's semen does not seem to improve
the reproductive outcomes in the subsequent cycle. STUDY FUNDING/COMPETING
INTERESTS: No extra-mural funding was obtained for this study. There are no
conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NA.
PMID- 27609984
TI - The effect of an immediate frozen embryo transfer following a freeze-all
protocol: a retrospective analysis from two centres.
AB - STUDY QUESTION: Does the timing of the first frozen embryo transfer (FET) after
gonadotropin-releasing hormone (GnRH) agonist triggering with the elective
cryopreservation of all embryos affect pregnancy outcome? SUMMARY ANSWER: FETs
performed immediately after a freeze-all cycle did not vary significantly from
delayed FETs in terms of pregnancy rates. WHAT IS KNOWN ALREADY: As interest in,
and use of, the freeze-all strategy expands in the field of reproductive
medicine, the optimal timing to perform the subsequent FET has become
increasingly important. Thus far, all clinical trials evaluating the efficacy of
the segmentation strategy have opted to electively defer the first FET for at
least one menstrual cycle. However, this mere empirical approach may cause
unnecessary distress to infertile patients eager to conceive as soon as possible.
STUDY DESIGN, SIZE AND DURATION: This retrospective cohort study included the
first FET cycle of all women who underwent a freeze-all protocol between October
2010 and October 2015 in two reproductive medicine centres (in Belgium and
Vietnam, respectively). PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of
333 FET cycles were included in the analysis. Following the freeze-all cycle, the
preparation of the endometrium consisted of the sequential administration of
oestradiol valerate and micronized vaginal progesterone. The start of the FET was
classified as either immediate (following the GnRH agonist withdrawal bleeding)
or delayed (by at least one menstrual cycle). Clinical pregnancy rate (CPR) was
the main outcome of our study. MAIN RESULTS AND THE ROLE OF CHANCE: Women in the
immediate FET group were slightly younger on average (30.9 +/- 4.1 versus 31.8 +/
4.3, P = 0.045) on the date of oocyte retrieval. Moreover, women in the
immediate FET group received a blastocyst transfer more frequently (53.4% versus
41.6%, P = 0.038) and had fewer embryos transferred on average compared to the
delayed FET group (1.8 +/- 0.8 versus 2.0 +/- 0.8, P = 0.013). CPR/FET was
marginally significantly higher in the immediate FET group in our crude analysis
(52.9% after immediate FET versus 41.6% after delayed FET, P = 0.046). In order
to assess if CPR/FET remained unaltered after adjusting for measured confounding,
we performed mixed-effects multivariable regression analysis. Timing of the FET
no longer affected significantly the CPR of the first FET in the adjusted
analysis (adjusted odds ratio (aOR): 0.62, 95% CI: 0.38-1.00; predicted CPR of
52.5% for immediate FET versus 41.8% for delayed FET). LIMITATIONS, REASONS FOR
CAUTION: The results are limited by the retrospective design and the potential
for unmeasured confounding. Furthermore, we only evaluated the effect of the FET
timing of the first FET on CPRs in artificially supplemented cycles and, thus,
the results should not be extrapolated to live birth rates or natural-cycle FETs.
WIDER IMPLICATIONS OF THE FINDINGS: This study offers a simple but potentially
relevant measure to increase patient satisfaction and adherence in couples who
seek to become pregnant both safely and as soon as possible. STUDY
FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors
have no conflicts of interest to declare.
PMID- 27609985
TI - Seminal plasma transforming growth factor-beta, activin A and follistatin
fluctuate within men over time.
AB - STUDY QUESTION: Do seminal plasma transforming growth factor-beta (TGFB)
cytokines vary within individuals over time, and does this relate to sperm
parameters, age or prior abstinence? SUMMARY ANSWER: Activin A and follistatin,
and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time,
in association with duration of abstinence. WHAT IS ALREADY KNOWN: Seminal plasma
TGFB cytokines can influence sperm function and reproductive success through
interactions with the female reproductive tract after coitus. Over time,
individual sperm parameters fluctuate considerably. Whether seminal fluid TGFB
cytokines vary similarly, and the determinants of any variance, is unknown. STUDY
DESIGN, SIZE, DURATION: Between two and seven semen samples were collected from
each of 14 fertile donors at 6-10 week intervals over the course of 12 months,
then seminal plasma cytokines and sperm parameters were measured.
PARTICIPANTS/MATERIALS, SETTING AND METHOD: The concentrations and total amounts
per ejaculate of TGFB1, TGFB2, TGFB3, activin A and follistatin were determined
using commercial assays. Sperm parameters were assessed according to WHO IV
standards. Mixed model analysis was utilised to determine the relative
contribution of between- and within-individual factors to the variance.
Relationships between cytokines and sperm parameters, as well as effect of age
and duration of abstinence, were investigated by correlation analysis. MAIN
RESULTS AND THE ROLE OF CHANCE: Within-individual variability contributed to the
total variance for all cytokines and sperm parameters, and was a stronger
determinant than between-individual variability for activin A and follistatin as
well as for total sperm concentration and sperm motility. Positive correlations
between each of the three TGFB isoforms, and activin and follistatin, suggest co
regulation of synthesis. Duration of abstinence influenced total content of
TGFB1, TGFB2, activin A and follistatin. TGFB1 correlated inversely with age.
LIMITATIONS, REASONS FOR CAUTION: A limited number of donors from a single clinic
were investigated. Clinical information on BMI, nutrition, smoking and other
lifestyle factors was unavailable. Further studies are required to determine
whether the findings can be generalised to larger populations and different
ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: These data reveal substantial
variation over time in seminal fluid cytokines and indicate that repeated
analyses are required to gain precise representative data on an individual's
status. Within-individual variation in seminal fluid components should be taken
into account when investigating seminal fluid cytokines. STUDY FUNDING/COMPETING
INTERESTS: This study was supported by grants from the National Health and
Medical Research Council of Australia, ID453556 and APP1041332. The authors have
no competing interests to disclose.
PMID- 27609986
TI - Parents' anxiety and depression symptoms after successful infertility treatment
and spontaneous conception: does singleton/twin pregnancy matter?
AB - STUDY QUESTION: Does mode of conception [spontaneous/after infertility treatment
(IT)], type of pregnancy (singleton/twin) and parent gender have an effect on
anxiety and depression levels and trajectories during pregnancy and the post
partum period? SUMMARY ANSWER: Conception after IT was associated with a
transitory increase in anxiety during the perinatal period for parents of
singletons, while for IT parents of twins higher levels of psychopathological
symptoms tended to persist during pregnancy and the post-partum period. WHAT IS
KNOWN ALREADY: Most previous studies have shown that successful IT is not
associated with poor psychological well-being during pregnancy and the post
partum period, but there is also some evidence for heightened pregnancy-related
anxiety, lower self-esteem and lower self-efficacy. Parents of twins experience
increased postnatal anxiety and depression. STUDY DESIGN, SIZE, DURATION: This
prospective longitudinal study assessed 267 couples (N = 534) at each trimester
of pregnancy, after childbirth and at 3 months post-partum.
PARTICIPANTS/MATERIALS, SETTING, METHOD: The sample comprised 36 couples who had
conceived after IT (19 twin pairs and 17 singletons) and 231 couples who had
conceived spontaneously (SC; 28 twin pairs and 203 singletons). Couples were
recruited at four public hospitals in Portugal, and self-report measures of
anxiety and depression symptoms were administered. MAIN RESULTS AND THE ROLE OF
CHANCE: IT parents reported higher anxiety after childbirth than parents who SC,
regardless of pregnancy type. IT parents of twins showed higher anxiety at mid
pregnancy, as well as higher anxiety and depression at 3 months post-partum than
IT parents of singletons. Among IT mothers, those who had twins exhibited higher
depression after childbirth than those who had singletons. Differences according
to mode of conception, pregnancy type and parents gender over time were also
noted. During pregnancy, IT parents of twins showed no significant change in
depression scores, while the other groups depression scores statistically
significantly decreased over time. From pregnancy to the post-partum period, (i)
IT parents showed an increase in anxiety scores, whereas SC parents exhibited no
changes in anxiety scores; (ii) IT women exhibited an increase in depression
scores, while SC women depression scores decreased. During the post-partum
period, IT and SC parents of twins showed no changes in anxiety scores, while IT
and SC parents of singletons anxiety scores declined. LIMITATIONS, REASONS FOR
CAUTION: Due to the small number of IT couples, the interpretation and
generalization of the results should be done with caution. WIDER IMPLICATIONS OF
THE FINDINGS: The adverse impact of IT on psychopathological symptoms depends
mostly on time and type of pregnancy, and is greater for twin pregnancies. These
findings are important for tailoring interventions that address parents' specific
needs at different moments. STUDY FUNDING/COMPETING INTERESTS: This work was
supported by a grant (SFRH/BD/40146/2007) to the first author from the FCT,
Foundation for Science and Technology (Portuguese Ministry of Education and
Science), by the Operational Program Science and Innovation 2010 (POCI 2010) of
the Community Support Board III, by FEDER Funds through the Operational
Competitiveness Programme, COMPETE, and through national funding from the FCT
under the projects: POCI/SAU-ESP/ 56397/2004 and PTDC/SAU/SAP/116738/2010. The
authors have no conflicts of interest.
PMID- 27609987
TI - Using in situ management to conserve biodiversity under climate change.
AB - Successful conservation will increasingly depend on our ability to help species
cope with climate change. While there has been much attention on accommodating or
assisting range shifts, less has been given to the alternative strategy of
helping species survive climate change through in situ management.Here we provide
a synthesis of published evidence examining whether habitat management can be
used to offset the adverse impacts on biodiversity of changes in temperature,
water availability and sea-level rise. Our focus is on practical methods whereby
the local environmental conditions experienced by organisms can be made more
suitable.Many studies suggest that manipulating vegetation structure can alter
the temperature and moisture conditions experienced by organisms, and several
demonstrate that these altered conditions benefit species as regional climatic
conditions become unsuitable. The effects of topography on local climatic
conditions are even better understood, but the alteration of topography as a
climate adaptation tool is not ingrained in conservation practice. Trials of
topographic alteration in the field should therefore be a priority for future
research.Coastal systems have the natural capacity to keep pace with climate
change, but require sufficient sediment supplies and space for landward migration
to do so. There is an extensive literature on managed realignment. While the
underlying rationale is simple, successful implementation requires careful
consideration of elevation and past land use. Even with careful management,
restored habitats may not attain the physical and biological attributes of
natural habitats. Synthesis and applications. The recent literature provides a
compelling case that some of the adverse effects of climate change can be offset
by appropriate management. However, much of the evidence for this is indirect and
too few studies provide empirical tests of the long-term effectiveness of these
management interventions. It is clear from the existing evidence that some
techniques have a higher risk of failure or unexpected outcomes than others and
managers will need to make careful choices about which to implement. We have
assessed the strength of evidence of these approaches in order to demonstrate to
conservation professionals the risks involved.
PMID- 27609988
TI - Modest enhancements to conventional grassland diversity improve the provision of
pollination services.
AB - Grassland for livestock production is a major form of land use throughout Europe
and its intensive management threatens biodiversity and ecosystem functioning in
agricultural landscapes. Modest increases to conventional grassland biodiversity
could have considerable positive impacts on the provision of ecosystem services,
such as pollination, to surrounding habitats.Using a field-scale experiment in
which grassland seed mixes and sward management were manipulated, complemented by
surveys on working farms and phytometer experiments, the impact of conventional
grassland diversity and management on the functional diversity and ecosystem
service provision of pollinator communities were investigated.Increasing plant
richness, by the addition of both legumes and forbs, was associated with
significant enhancements in the functional diversity of grassland pollinator
communities. This was associated with increased temporal stability of flower
visitor interactions at the community level. Visitation networks revealed pasture
species Taraxacum sp. (Wigg.) (dandelion) and Cirsium arvense (Scop.) (creeping
thistle) to have the highest pollinator visitation frequency and richness.
Cichorium intybus (L.) (chichory) was highlighted as an important species having
both high pollinator visitation and desirable agronomic properties.Increased
sward richness was associated with an increase in the pollination of two
phytometer species; Fragaria * ananassa (strawberry) and Silene dioica (red
campion), but not Vicia faba (broad bean). Enhanced functional diversity,
richness and abundance of the pollinator communities associated with more diverse
neighbouring pastures were found to be potential mechanisms for improved
pollination. Synthesis and applications. A modest increase in conventional
grassland plant diversity with legumes and forbs, achievable with the expertise
and resources available to most grassland farmers, could enhance pollinator
functional diversity, richness and abundance. Moreover, our results suggest that
this could improve pollination services and consequently surrounding crop yields
(e.g. strawberry) and wildflower reproduction in agro-ecosystems.
PMID- 27609989
TI - Design of Stretchable Electronics Against Impact.
AB - Stretchable electronics offer soft, biocompatible mechanical properties; these
same properties make them susceptible to device failure associated with physical
impact. This paper studies designs for stretchable electronics that resist
failure from impacts due to incorporation of a viscoelastic encapsulation layer.
Results indicate that the impact resistance depends on the thickness and
viscoelastic properties of the encapsulation layer, as well as the duration of
impact. An analytic model for the critical thickness of the encapsulation layer
is established. It is shown that a commercially available, low modulus silicone
material offers viscous properties that make it a good candidate as the
encapsulation layer for stretchable electronics.
PMID- 27609990
TI - Automatic Detection of Endotracheal Intubation During the Anesthesia Procedure.
AB - This paper is concerned with the mathematical modeling and detection of
endotracheal (ET) intubation in children under general anesthesia during surgery.
In major pediatric surgeries, the airway is often secured with an endotracheal
tube (ETT) followed by initiation of mechanical ventilation. Clinicians utilize
auscultation of breath sounds and capnography to verify correct ETT placement.
However, anesthesia providers often delay timely charting of ET intubation. This
latency in event documentation results in decreased efficacy of clinical decision
support systems. In order to target this problem, we collected real inpatient
data and designed an algorithm to accurately detect the intubation time within
the clinically valid range; the results show that we are able to achieve high
accuracy in more than 96% of the cases. Automatic detection of ET intubation time
would thus enhance better real-time data capture to support future improvement in
clinical decision support systems.
PMID- 27609991
TI - Consistent, small effects of treefall disturbances on the composition and
diversity of four Amazonian forests.
AB - Understanding the resilience of moist tropical forests to treefall disturbance
events is important for understanding the mechanisms that underlie species
coexistence and for predicting the future composition of these ecosystems. Here,
we test whether variation in the functional composition of Amazonian forests
determines their resilience to disturbance.We studied the legacy of natural
treefall disturbance events in four forests across Amazonia that differ
substantially in functional composition. We compared the composition and
diversity of all free-standing woody stems 2-10 cm diameter in previously
disturbed and undisturbed 20 * 20 m subplots within 55, one-hectare, long-term
forest inventory plots.Overall, stem number increased following disturbance, and
species and functional composition shifted to favour light-wooded, small-seeded
taxa. Alpha-diversity increased, but beta-diversity was unaffected by
disturbance, in all four forests.Changes in response to disturbance in both
functional composition and alpha-diversity were, however, small (2 - 4% depending
on the parameter) and similar among forests. Synthesis. This study demonstrates
that variation in the functional composition of Amazonian forests does not lead
to large differences in the response of these forests to treefall disturbances,
and overall, these events have a minor role in maintaining the diversity of these
ecosystems.
PMID- 27609992
TI - Drought history affects grassland plant and microbial carbon turnover during and
after a subsequent drought event.
AB - Drought periods are projected to become more severe and more frequent in many
European regions. While effects of single strong droughts on plant and microbial
carbon (C) dynamics have been studied in some detail, impacts of recurrent
drought events are still little understood.We tested whether the legacy of
extreme experimental drought affects responses of plant and microbial C and
nitrogen (N) turnover to further drought and rewetting. In a mountain grassland,
we conducted a 13C pulse-chase experiment during a naturally occurring drought
and rewetting event in plots previously exposed to experimental droughts and in
ambient controls (AC). After labelling, we traced 13C below-ground allocation and
incorporation into soil microbes using phospholipid fatty acid biomarkers.Drought
history (DH) had no effects on the standing shoot and fine root plant biomass.
However, plants with experimental DH displayed decreased shoot N concentrations
and increased fine root N concentrations relative to those in AC. During the
natural drought, plants with DH assimilated and allocated less 13C below-ground;
moreover, fine root respiration was reduced and not fuelled by fresh C compared
to plants in AC.Regardless of DH, microbial biomass remained stable during
natural drought and rewetting. Although microbial communities initially differed
in their composition between soils with and without DH, they responded to the
natural drought and rewetting in a similar way: gram-positive bacteria increased,
while fungal and gram-negative bacteria remained stable. In soils with DH, a
strongly reduced uptake of recent plant-derived 13C in microbial biomarkers was
observed during the natural drought, pointing to a smaller fraction of active
microbes or to a microbial community that is less dependent on plant C.
Synthesis. Drought history can induce changes in above- vs. below-ground plant N
concentrations and affect the response of plant C turnover to further droughts
and rewetting by decreasing plant C uptake and below-ground allocation. DH does
not affect the responses of the microbial community to further droughts and
rewetting, but alters microbial functioning, particularly the turnover of recent
plant-derived carbon, during and after further drought periods.
PMID- 27609993
TI - Palaeoecology of a billion-year-old non-marine cyanobacterium from the Torridon
Group and Nonesuch Formation.
AB - A new chroococcalean cyanobacterium is described from approximately 1-billion
year-old non-marine deposits of the Torridonian Group of Scotland and the
Nonesuch Formation of Michigan, USA. Individual cells of the new microfossil,
Eohalothece lacustrina gen. et sp. nov., are associated with benthic microbial
biofilms, but the majority of samples are recovered in palynological preparations
in the form of large, apparently planktonic colonies, similar to extant species
of Microcystis. In the Torridonian, Eohalothece is associated with phosphatic
nodules, and we have developed a novel hypothesis linking Eohalothece to
phosphate deposition in ancient freshwater settings. Extant cyanobacteria can be
prolific producers of extracellular microcystins, which are non-ribosomal
polypeptide phosphatase inhibitors. Microcystins may have promoted the retention
and concentration of sedimentary organic phosphate prior to mineralization of
francolite and nodule formation. This has a further implication that the
Torridonian lakes were nitrogen limited as the release of microcystins is
enhanced under such conditions today. The abundance and wide distribution of
Eohalothece lacustrina attests to the importance of cyanobacteria as oxygen
producing photoautotrophs in lacustrine ecosystems at the time of the
Mesoproterozoic-Neoproterozoic transition.
PMID- 27609994
TI - Multivariate emulation of computer simulators: model selection and diagnostics
with application to a humanitarian relief model.
AB - We present a common framework for Bayesian emulation methodologies for
multivariate output simulators, or computer models, that employ either parametric
linear models or non-parametric Gaussian processes. Novel diagnostics suitable
for multivariate covariance separable emulators are developed and techniques to
improve the adequacy of an emulator are discussed and implemented. A variety of
emulators are compared for a humanitarian relief simulator, modelling aid
missions to Sicily after a volcanic eruption and earthquake, and a sensitivity
analysis is conducted to determine the sensitivity of the simulator output to
changes in the input variables. The results from parametric and non-parametric
emulators are compared in terms of prediction accuracy, uncertainty
quantification and scientific interpretability.
PMID- 27609995
TI - Assessing water resource system vulnerability to unprecedented hydrological
drought using copulas to characterize drought duration and deficit.
AB - Global climate models suggest an increase in evapotranspiration, changing storm
tracks, and moisture delivery in many parts of the world, which are likely to
cause more prolonged and severe drought, yet the weakness of climate models in
modeling persistence of hydroclimatic variables and the uncertainties associated
with regional climate projections mean that impact assessments based on climate
model output may underestimate the risk of multiyear droughts. In this paper, we
propose a vulnerability-based approach to test water resource system response to
drought. We generate a large number of synthetic streamflow series with different
drought durations and deficits and use them as input to a water resource system
model. Marginal distributions of the streamflow for each month are generated by
bootstrapping the historical data, while the joint probability distributions of
consecutive months are constructed using a copula-based method. Droughts with
longer durations and larger deficits than the observed record are generated by
perturbing the copula parameter and by adopting an importance sampling strategy
for low flows. In this way, potential climate-induced changes in monthly
hydrological persistence are factored into the vulnerability analysis. The method
is applied to the London water system (England) to investigate under which
drought conditions severe water use restrictions would need to be imposed.
Results indicate that the water system is vulnerable to drought conditions
outside the range of historical events. The vulnerability assessment results were
coupled with climate model information to compare alternative water management
options with respect to their vulnerability to increasingly long and severe
drought.
PMID- 27609996
TI - Attribution of regional flood changes based on scaling fingerprints.
AB - Changes in the river flood regime may be due to atmospheric processes (e.g.,
increasing precipitation), catchment processes (e.g., soil compaction associated
with land use change), and river system processes (e.g., loss of retention volume
in the floodplains). This paper proposes a new framework for attributing flood
changes to these drivers based on a regional analysis. We exploit the scaling
characteristics (i.e., fingerprints) with catchment area of the effects of the
drivers on flood changes. The estimation of their relative contributions is
framed in Bayesian terms. Analysis of a synthetic, controlled case suggests that
the accuracy of the regional attribution increases with increasing number of
sites and record lengths, decreases with increasing regional heterogeneity,
increases with increasing difference of the scaling fingerprints, and decreases
with an increase of their prior uncertainty. The applicability of the framework
is illustrated for a case study set in Austria, where positive flood trends have
been observed at many sites in the past decades. The individual scaling
fingerprints related to the atmospheric, catchment, and river system processes
are estimated from rainfall data and simple hydrological modeling. Although the
distributions of the contributions are rather wide, the attribution identifies
precipitation change as the main driver of flood change in the study region.
Overall, it is suggested that the extension from local attribution to a regional
framework, including multiple drivers and explicit estimation of uncertainty,
could constitute a similar shift in flood change attribution as the extension
from local to regional flood frequency analysis.
PMID- 27609997
TI - A new upper limit to the field-aligned potential near Titan.
AB - Neutral particles dominate regions of the Saturn magnetosphere and locations near
several of Saturn's moons. Sunlight ionizes neutrals, producing photoelectrons
with characteristic energy spectra. The Cassini plasma spectrometer electron
spectrometer has detected photoelectrons throughout these regions, where
photoelectrons may be used as tracers of magnetic field morphology. They also
enhance plasma escape by setting up an ambipolar electric field, since the
relatively energetic electrons move easily along the magnetic field. A similar
mechanism is seen in the Earth's polar wind and at Mars and Venus. Here we
present a new analysis of Titan photoelectron data, comparing spectra measured in
the sunlit ionosphere at ~1.4 Titan radii (RT) and at up to 6.8 RT away. This
results in an upper limit on the potential of 2.95 V along magnetic field lines
associated with Titan at up to 6.8 RT, which is comparable to some similar
estimates for photoelectrons seen in Earth's magnetosphere.
PMID- 27609998
TI - Asymmetries observed in Saturn's magnetopause geometry.
AB - For over 10 years, the Cassini spacecraft has patrolled Saturn's magnetosphere
and observed its magnetopause boundary over a wide range of prevailing solar wind
and interior plasma conditions. We now have data that enable us to resolve a
significant dawn-dusk asymmetry and find that the magnetosphere extends farther
from the planet on the dawnside of the planet by 7 +/- 1%. In addition, an
opposing dawn-dusk asymmetry in the suprathermal plasma pressure adjacent to the
magnetopause has been observed. This probably acts to reduce the size asymmetry
and may explain the discrepancy between the degree of asymmetry found here and a
similar asymmetry found by Kivelson and Jia (2014) using MHD simulations.
Finally, these observations sample a wide range of season, allowing the
"intrinsic" polar flattening (14 +/- 1%) caused by the magnetodisc to be
separated from the seasonally induced north-south asymmetry in the magnetopause
shape found theoretically (5 +/- 1% when the planet's magnetic dipole is tilted
away from the Sun by 10-17 degrees ).
PMID- 27609999
TI - The energy-based scaling of a thin current sheet: Case study.
AB - The influence of average plasma energy E~ on the half thickness l of a thin
current sheet (TCS) is investigated for three cases of TCSs crossings. The value
of l was estimated from the magnetic field data by means of Cluster observations.
The obtained scaling values for TCSs, Z~=l/rhoT, where rhoT is the thermal Larmor
radius, were compared with the scaling ZMU=22E~/T, where E~ and T are the average
plasma energy and the temperature of plasma, which assumes a specific dynamics
(conservation of magnetic flux through the trajectory segment) of the current
carriers. The comparison of Z~ and ZMU shows a good agreement.
PMID- 27610000
TI - Perturbations in growth trajectory due to early diet affect age-related
deterioration in performance.
AB - Fluctuations in early developmental conditions can cause changes in growth
trajectories that subsequently affect the adult phenotype. Here, we investigated
whether compensatory growth has long-term consequences for patterns of
senescence.Using three-spined sticklebacks (Gasterosteus aculeatus), we show that
a brief period of dietary manipulation in early life affected skeletal growth
rate not only during the manipulation itself, but also during a subsequent
compensatory phase when fish caught up in size with controls.However, this growth
acceleration influenced swimming endurance and its decline over the course of the
breeding season, with a faster decline in fish that had undergone faster growth
compensation.Similarly, accelerated growth led to a more pronounced reduction in
the breeding period (as indicated by the duration of sexual ornamentation) over
the following two breeding seasons, suggesting faster reproductive senescence.
Parallel experiments showed a heightened effect of accelerated growth on these
age-related declines in performance if the fish were under greater time stress to
complete their compensation prior to the breeding season.Compensatory growth led
to a reduction in median life span of 12% compared to steadily growing controls.
While life span was independent of the eventual adult size attained, it was
negatively correlated with the age-related decline in swimming endurance and
sexual ornamentation.These results, complementary to those found when growth
trajectories were altered by temperature rather than dietary manipulations, show
that the costs of accelerated growth can last well beyond the time over which
growth rates differ and are affected by the time available until an approaching
life-history event such as reproduction.
PMID- 27610001
TI - Universal food security program and nutritional intake: Evidence from the hunger
prone KBK districts in Odisha.
AB - This article provides evidence on the role of consumer food subsidies in
improving nutritional intake and diet quality by evaluating the expansion of the
government food assistance program coverage in the hunger prone state of Odisha
in India. In 8 districts of Odisha, popularly known as the Kalahandi-Balangir
Koraput (KBK) region which is notable for extreme poverty and starvation deaths,
the government did away with the targeted food assistance program in 2008 and
made the scheme universal. Using a Difference-in-Difference methodology over two
repeated cross sectional household surveys, this article finds that the shift
from targeted to a universal food security program in the KBK region of Odisha
has led to an improvement in the household nutritional intake and diet quality.
Further examination suggests that proportion of households consuming below the
recommended dietary allowance of calorie, fats and protein has declined
significantly in this region post the intervention.
PMID- 27610002
TI - Disentangling the contribution of multiple land covers to fire-mediated carbon
emissions in Amazonia during the 2010 drought.
AB - In less than 15 years, the Amazon region experienced three major droughts. Links
between droughts and fires have been demonstrated for the 1997/1998, 2005, and
2010 droughts. In 2010, emissions of 510 +/- 120 Tg C were associated to fire
alone in Amazonia. Existing approaches have, however, not yet disentangled the
proportional contribution of multiple land cover sources to this total. We
develop a novel integration of multisensor and multitemporal satellite-derived
data on land cover, active fires, and burned area and an empirical model of fire
induced biomass loss to quantify the extent of burned areas and resulting biomass
loss for multiple land covers in Mato Grosso (MT) state, southern Amazonia-the
2010 drought most impacted region. We show that 10.77% (96,855 km2) of MT burned.
We estimated a gross carbon emission of 56.21 +/- 22.5 Tg C from direct
combustion of biomass, with an additional 29.4 +/- 10 Tg C committed to be
emitted in the following years due to dead wood decay. It is estimated that old
growth forest fires in the whole Brazilian Legal Amazon (BLA) have contributed to
14.81 Tg of C (11.75 Tg C to 17.87 Tg C) emissions to the atmosphere during the
2010 fire season, with an affected area of 27,555 km2. Total C loss from the 2010
fires in MT state and old-growth forest fires in the BLA represent, respectively,
77% (47% to 107%) and 86% (68.2% to 103%) of Brazil's National Plan on Climate
Change annual target for Amazonia C emission reductions from deforestation.
PMID- 27610004
TI - Diet-Intestinal Microbiota Axis in Osteoarthritis: A Possible Role.
AB - Intestinal microbiota is highly involved in host physiology and pathology through
activity of the microbiome and its metabolic products. Osteoarthritis (OA) is a
common form of arthritis characterized by articular cartilage destruction and
osteophyte formation. Although various person-level risk factors, such as age,
sex, and obesity, have been proposed for the pathogenesis of OA, the underlying
links between these person-level factors and OA are still enigmatic. Based on the
current understanding in the crosstalk between intestinal microbiota and these
risk factors, intestinal microbiota could be considered as a major hidden risk
factor that provides a unifying mechanism to explain the involvement of these
person-level risk factors in OA.
PMID- 27610003
TI - Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17.
AB - This study was conducted to explore the effects of interferon tau (IFNT) on the
intestinal microbiota and expression of interleukin 17 (IL-17) in the intestine
of mice. IFNT supplementation increased microbial diversity in the jejunum and
ileum but decreased microbial diversity in the feces. IFNT supplementation
influenced the composition of the intestinal microbiota as follows: (1)
decreasing the percentage of Firmicutes and increasing Bacteroidetes in the
jejunum and ileum; (2) enhancing the percentage of Firmicutes but decreasing
Bacteroidetes in the colon and feces; (3) decreasing Lactobacillus in the jejunum
and ileum; (4) increasing the percentage of Blautia, Bacteroides, Alloprevotella,
and Lactobacillus in the colon; and (5) increasing the percentage of
Lactobacillus, Bacteroides, and Allobaculum, while decreasing Blautia in the
feces. Also, IFNT supplementation decreased the expression of IL-17 in the
intestines of normal mice and of an intestinal pathogen infected mice. In
conclusion, IFNT supplementation modulates the intestinal microbiota and
intestinal IL-17 expression, indicating the applicability of IFNT to treat the
intestinal diseases involving IL-17 expression and microbiota.
PMID- 27610005
TI - Exaggerated IL-15 and Altered Expression of foxp3+ Cell-Derived Cytokines
Contribute to Enhanced Colitis in Nlrp3-/- Mice.
AB - The pathogenesis of Crohn's disease (CD) involves defects in the innate immune
system, impairing responses to microbes. Studies have revealed that mutations
NLRP3 are associated with CD. We reported previously that Nlrp3-/- mice were more
susceptible to colitis and exhibited reduced colonic IL-10 expression. In the
current study, we sought to determine how the loss of NLRP3 might be altering the
function of regulatory T cells, a major source of IL-10. Colitis was induced in
wild-type (WT) and Nlrp3-/- mice by treatment with dextran sulphate sodium (DSS).
Lamina propria (LP) cells were assessed by flow cytometry and cytokine expression
was assessed. DSS-treated Nlrp3-/- mice exhibited increased numbers of colonic
foxp3+ T cells that expressed significantly lower levels of IL-10 but increased
IL-17. This was associated with increased expression of colonic IL-15 and
increased surface expression of IL-15 on LP dendritic cells. Neutralizing IL-15
in Nlrp3-/- mice attenuated the severity of colitis, decreased the number of
colonic foxp3+ cells, and reduced the colonic expression of IL-12p40 and IL-17.
These data suggest that the NLRP3 inflammasome can regulate intestinal
inflammation through noncanonical mechanisms, providing additional insight as to
how NLRP3 variants may contribute to the pathogenesis of CD.
PMID- 27610007
TI - Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of
Experimental Autoimmune Encephalomyelitis.
AB - Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces
cardinal signs of clinical, histopathological, and immunological features found
in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main
inflammatory phases occurring during EAE development, possibly by secreting
several autacoids and proteases. Among the latter, the chymase mouse mast cell
protease 4 (mMCP-4) can contribute to the inflammatory response by producing
endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4
on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout
(KO) mice were immunized with MOG35-55 plus complete Freund's adjuvant followed
by pertussis toxin. Immunized WT mice presented an initial acute phase
characterized by progressive increases in clinical score, which were
significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal
myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE
triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive
ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO
congeners. Together, the present study supports a role for mMCP-4 in the early
inflammatory phases of the disease in a mouse model of MS.
PMID- 27610006
TI - TGF-beta1/Smads and miR-21 in Renal Fibrosis and Inflammation.
AB - Renal fibrosis, irrespective of its etiology, is a final common stage of almost
all chronic kidney diseases. Increased apoptosis, epithelial-to-mesenchymal
transition, and inflammatory cell infiltration characterize the injured kidney.
On the molecular level, transforming growth factor-beta1 (TGF-beta1)-Smad3
signaling pathway plays a central role in fibrotic kidney disease. Recent
findings indicate the prominent role of microRNAs, small noncoding RNA molecules
that inhibit gene expression through the posttranscriptional repression of their
target mRNAs, in different pathologic conditions, including renal
pathophysiology. miR-21 was also shown to play a dynamic role in inflammatory
responses and in accelerating injury responses to promote organ failure and
fibrosis. Understanding the cellular and molecular bases of miR-21 involvement in
the pathogenesis of kidney diseases, including inflammatory reaction, could be
crucial for their early diagnosis. Moreover, the possibility of influencing miR
21 level by specific antagomirs may be considered as an approach for treatment of
renal diseases.
PMID- 27610008
TI - Identification of a Novel lincRNA-p21-miR-181b-PTEN Signaling Cascade in Liver
Fibrosis.
AB - Previously, we found that long intergenic noncoding RNA-p21 (lincRNA-p21)
inhibits hepatic stellate cell (HSC) activation and liver fibrosis via p21.
However, the underlying mechanism of the antifibrotic role of lincRNA-p21 in
liver fibrosis remains largely unknown. Here, we found that lincRNA-p21
expression was significantly downregulated during liver fibrosis. In LX-2 cells,
the reduction of lincRNA-p21 induced by TGF-beta1 was in a dose- and time
dependent manner. lincRNA-p21 expression was reduced in liver tissues from
patients with liver cirrhosis when compared with that of healthy controls.
Notably, lincRNA-p21 overexpression contributed to the suppression of HSC
activation. lincRNA-p21 suppressed HSC proliferation and induced a significant
reduction in alpha-SMA and type I collagen. All these effects induced by lincRNA
p21 were blocked down by the loss of PTEN, suggesting that lincRNA-p21 suppressed
HSC activation via PTEN. Further study demonstrated that microRNA-181b (miR-181b)
was involved in the effects of lincRNA-p21 on HSC activation. The effects of
lincRNA-p21 on PTEN expression and HSC activation were inhibited by miR-181b
mimics. We demonstrated that lincRNA-p21 enhanced PTEN expression by
competitively binding miR-181b. In conclusion, our results disclose a novel
lincRNA-p21-miR-181b-PTEN signaling cascade in liver fibrosis and suggest lincRNA
p21 as a promising molecular target for antifibrosis therapy.
PMID- 27610009
TI - Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic
steatohepatitis?
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease
worldwide, affecting approximately one third of the Western world. It consists of
a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic
steatohepatitis (NASH), which consists of steatosis, ballooning injury and
inflammation. Despite an alarming growth in the statistics surrounding NAFLD,
there are as yet no effective therapies for its treatment. Innate immune
signaling has been thought to play a significant role in initiating and
augmenting hepatic inflammation, contributing to the transition from nonalcoholic
fatty liver to NASH. An immune response is triggered by countless signals called
damage-associated molecular patterns (DAMPs) elicited by lipid-laden and damaged
hepatocytes, which are recognized by pattern recognition receptors (PRRs) on
hepatic immune cells to initiate inflammatory signaling. In this editorial, in
addition to summarizing innate immune signaling in NAFLD and discussing potential
therapies that target innate immune pathways, we have described a recent study
that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic
PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying
a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9
reverses NASH, paving the way for the development of future NASH therapy.
PMID- 27610010
TI - Endoscopic and non-endoscopic approaches for the management of radiation-induced
rectal bleeding.
AB - Pelvic radiation is a commonly utilized treatment for malignancy of the
genitourinary and lower gastrointestinal tract. Radiation proctitis and the
resultant clinical picture varies from asymptomatic to potentially life
threatening. Similarly, treatment options also vary greatly, from medical therapy
to surgical intervention. Commonly utilized medical therapy includes sucralfate
enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants,
short-chain fatty acids, formalin instillation and fractionated hyperbaric
oxygen. More invasive treatments include endoscopic-based, focally ablative
interventions such as dilation, heater and bipolar cautery, neodymium/yttrium
aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation.
Despite its relatively common frequency, there is a dearth of existing literature
reporting head-to-head comparisons of the various treatment options via a
randomized controlled approach. The purpose of our review was to present the
reader a consolidation of the existing evidence-based literature with the goal of
highlighting the comparative effectiveness and risks of the various treatment
approaches. Finally, we outline a pragmatic approach to the treatment of
radiation proctitis. In light of the lack of randomized data, our goal is to
pursue as least invasive an approach as possible, with escalation of care
tailored to the severity of the patient's symptoms. For those cases that are
clinically asymptomatic or only mildly symptomatic, observation or medical
management can be considered. Once a patient fails such management or symptoms
become more severe, invasive procedures such as endoscopically based focal
ablation or surgical intervention can be considered. Although not all
recommendations are supported by level I evidence, reported case series and
single-institutional studies in the literature suggest that successful treatment
with cessation of symptoms can be obtained in the majority of cases.
PMID- 27610012
TI - Metabolic aspects of adult patients with nonalcoholic fatty liver disease.
AB - Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver
disease and it encompasses a spectrum from simple steatosis to steatohepatitis,
fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and
its progression are probably due to a metabolic profile expressed within the
context of a genetic predisposition and is associated with a higher energy
intake. The metabolic syndrome (MS) is a cluster of metabolic alterations
associated with an increased risk for the development of cardiovascular diseases
and diabetes. NAFLD patients have more than one feature of the MS, and now they
are considered the hepatic components of the MS. Several scientific advances in
understanding the association between NAFLD and MS have identified insulin
resistance (IR) as the key aspect in the pathophysiology of both diseases. In the
multi parallel hits theory of NAFLD pathogenesis, IR was described to be central
in the predisposition of hepatocytes to be susceptible to other multiple
pathogenetic factors. The recent knowledge gained from these advances can be
applied clinically in the prevention and management of NAFLD and its associated
metabolic changes. The present review analyses the current literature and
highlights the new evidence on the metabolic aspects in the adult patients with
NAFLD.
PMID- 27610011
TI - FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic
cancer.
AB - Pancreatic cancer is an extremely aggressive disease; although progress has been
made in the last few years, the prognosis of these patients remains dismal.
FOLFIRINOX is now considered a standard treatment in first-line setting, since it
demonstrated an improved overall and progression-free survival vs gemcitabine
alone. However, the enthusiasm over the benefit of this three-drug regimen is
tempered by the associated increased toxicity profile, and many efforts have been
made to improve the feasibility of this schedule. After a more recent phase III
trial showing an improved outcome over gemcitabine, the combination of
gemcitabine/nab-paclitaxel emerged as another standard first-line treatment.
However, this treatment is also associated with more side effects. In addition,
despite initial promising data on the predictive role of SPARC levels, recent
studies showed that these levels are not associated with nab-paclitaxel efficacy.
The choice to use this treatment over FOLFIRINOX is therefore a topic of debate,
also because no validated biomarkers to guide FOLFIRINOX treatment are available.
In the era of actionable mutations and target agents it would be desirable to
identify molecular factors or biomarkers to predict response to therapy in order
to maximize the efficacy of treatment and avoid useless toxic effects for non
responding patients. However, until today the milestone of treatment for
pancreatic cancer remains chemotherapy combinations, without predictive or
monitoring tools existing to optimize therapy. This review analyzes the state-of
the-art treatments, promises and limitations of targeted therapies, ongoing
trials and future perspectives, including potential role of microRNAs as
predictive biomarkers.
PMID- 27610013
TI - Roles of hepatocyte nuclear factors in hepatitis B virus infection.
AB - Approximately 350 million people are estimated to be persistently infected with
hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by
employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs.
Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide
analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these
treatments rarely cure CHB because they are unable to inhibit cccDNA
transcription and inhibit only a late stage in the HBV life cycle (the reverse
transcription step in the nucleocapsid). Therefore, an understanding of the
factors regulating cccDNA transcription is required to stop this process. Among
numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles
in cccDNA transcription, especially in the generation of viral genomic RNA, a
template for HBV replication. Therefore, proper control of HNF function could
lead to the inhibition of HBV replication. In this review, we summarize and
discuss the current understanding of the roles of HNFs in the HBV life cycle and
the upstream factors that regulate HNFs. This knowledge will enable the
identification of new therapeutic targets to cure CHB.
PMID- 27610014
TI - Hepatitis E: Discovery, global impact, control and cure.
AB - Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir,
India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member
of family Hepeviridae. The virus has marked heterogeneity and infects many
animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and
cutthroat trout. Hepatitis E is a disease with a major global impact and has two
distinct epidemiological patterns. Hepatitis E is an imperative health issue in
developing nations, transmitted through sullied water and happens most every now
in young adults. The disease is particularly severe during pregnancy and in
people with underlying liver cirrhosis. Autochthonous hepatitis E is increasingly
recognized in developed countries. The virus infects domestic pigs, wild boar and
Sika deer in these countries. HEV infections in humans occur by eating the
undercooked game flesh, raw liver from supermarkets and Figatelli sausages. Blood
transfusion-associated HEV infections occur in many countries and screening of
donors for HEV RNA is under consideration. Hepatitis E causes a number of
extrahepatic diseases, including a wide spectrum of neurological syndromes. HEV
genotype 3 causes prolonged viremia, chronic hepatitis, liver fibrosis and
cirrhosis in organ transplant patients. The virus is amenable to ribavirin
monotherapy and most patients clear the virus in a few weeks. Hepatitis E vaccine
-239, marketed in China, has shown high efficacy with sustained protection for
over four years.
PMID- 27610017
TI - Weight loss endoscopy: Development, applications, and current status.
AB - Obesity and its comorbidities - including diabetes and obstructive sleep apnea -
have taken a large and increasing toll on the United States and the rest of the
world. The availability of commercial, clinical, and operative therapies for
weight management have not been effective at a societal level. Endoscopic
bariatric therapy is gaining acceptance as more effective than diet and lifestyle
measures, and less invasive than bariatric surgery. Various endoscopic therapies
are analogues of the restrictive or bypass components of bariatric surgery,
utilizing gastric remodeling or intestinal anastomosis to achieve proven weight
loss and metabolic benefits. Others, such as aspiration therapy, employ novel
mechanisms of action. Intragastric balloons have recently been approved by the
United States Food and Drug Administration, and a number of other technologies
have completed large multicenter trials (such as AspireAssist aspiration therapy
and Primary Obesity Surgery Endolumenal). Endoscopic sleeve gastroplasty and
transoral outlet reduction for endoscopic revision of gastric bypass have proven
safe and effective in a number of studies. As devices are approved for use, data
will continue to accumulate for safety, effectiveness, and cost effectiveness.
Bariatric endoscopists should be prepared to appropriately target and apply
various endoscopic bariatric therapies in the context of a comprehensive long
term weight management program.
PMID- 27610015
TI - Therapeutic potential of targeting acinar cell reprogramming in pancreatic
cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the
fourth leading cause of cancer death in the United States. Treating this life
threatening disease remains challenging due to the lack of effective prognosis,
diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be
the origin of PDAC. During pancreatitis or combined with activating KRas(G12D)
mutation, acinar cells lose their cellular identity and undergo a
transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming
duct cells which may then transform into pancreatic intraepithelial neoplasia
(PanIN) and eventually PDAC. During ADM, the activation of mitogen-activated
protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling
inhibits the transcription of acinar-specific genes, including Mist and amylase,
but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition
of this transdifferentiation process hinders the development of PanIN and PDAC.
In addition, the transdifferentiated cells regain acinar identity, indicating ADM
may be a reversible process. This provides a new therapeutic direction in
treating PDAC through cancer reprogramming. Many studies have already
demonstrated the success of switching PanIN/PDAC back to normal cells through the
use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this
review, we discuss the signaling pathways involved in ADM and the therapeutic
potential of targeting reprogramming in order to treat PDAC.
PMID- 27610018
TI - Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic
adenocarcinoma.
AB - Liposome, albumin and polymer polyethylene glycol are nanovector formulations
successfully developed for anti-cancer drug delivery. There are significant
differences in pharmacokinetics, efficacy and toxicity between pre- and post
nanovector modification. The alteration in clinical pharmacology is instrumental
for the future development of nanovector-based anticancer therapeutics. We have
reviewed the results of clinical studies and translational research in nanovector
based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including
nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore,
we have appraised the ongoing studies incorporating novel agents with
nanomedicines in the treatment of pancreatic adenocarcinoma.
PMID- 27610016
TI - Research progress on chemopreventive effects of phytochemicals on colorectal
cancer and their mechanisms.
AB - Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality
rates worldwide and has become a global health problem. The conventional
radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but
also causes side effects. Many studies have shown that adequate intake of fruits
and vegetables in the diet may have a protective effect on CRC occurrence,
possibly due to the special biological protective effect of the phytochemicals in
these foods. Numerous in vitro and in vivo studies have demonstrated that
phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles
by regulating specific signaling pathways and molecular markers to inhibit the
occurrence and development of CRC. This review summarizes the progress on CRC
prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and
elaborates on the specific underlying mechanisms. Thus, we believe that
phytochemicals might provide a novel therapeutic approach for CRC prevention, but
future clinical studies are needed to confirm the specific preventive effect of
phytochemicals on cancer.
PMID- 27610019
TI - Application of stapling devices in liver surgery: Current status and future
prospects.
AB - The liver is a vascular-rich solid organ. Safe and effective dissection of the
vessels and liver parenchyma, and control of intraoperative bleeding are the main
concerns when performing liver resection. Several studies have confirmed that
intraoperative blood loss and postoperative transfusion are predictors of
postoperative morbidity and mortality in liver surgery. Various methods and
instruments have been developed during hepatectomy. Stapling devices are crucial
for safe and rapid anastomosis. They are used to divide hepatic veins and portal
branches, and to transect liver parenchyma in open liver resection. In recent
years, laparoscopic liver surgery has developed rapidly, and is now preferred by
many surgeons. Stapling devices have also been gradually introduced in
laparoscopic liver surgery, from dividing vascular and biliary structures to
parenchymal transection. This may be because staplers make manipulation more
simple, rapid and safe. Even in single incision laparoscopic surgery, which is
recognized as a new minimally invasive technique, staplers are also utilized,
especially in left lateral hepatectomy. For safe application of stapling devices
in liver surgery, more related designs and modifications, such as application of
a suitable laparoscopic articulating liver tissue crushing device, a staple line
reinforcement technique with the absorbable polymer membrane or radiofrequency
ablation assistance, are still needed. More randomized studies are needed to
demonstrate the benefits and find broader indications for the use of stapling
devices, to help expand their application in liver surgery.
PMID- 27610020
TI - Current understanding concerning intestinal stem cells.
AB - In mammals, the intestinal epithelium is a tissue that contains two distinct
pools of stem cells: active intestinal stem cells and reserve intestinal stem
cells. The former are located in the crypt basement membrane and are responsible
for maintaining epithelial homeostasis under intact conditions, whereas the
latter exhibit the capacity to facilitate epithelial regeneration after injury.
These two pools of cells can convert into each other, maintaining their
quantitative balance. In terms of the active intestinal stem cells, their
development into functional epithelium is precisely controlled by the following
signaling pathways: Wnt/beta-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad.
However, mutations in some of the key regulator genes associated with these
signaling pathways, such as APC, Kras and Smad4, are also highly associated with
gut malformations. At this point, clarifying the biological characteristics of
intestinal stem cells will increase the feasibility of preventing or treating
some intestinal diseases, such as colorectal cancer. Moreover, as preclinical
data demonstrate the therapeutic effects of colon stem cells on murine models of
experimental colitis, the prospects of stem cell-based regenerative treatments
for ulcerous lesions in the gastrointestinal tract will be improved all the same.
PMID- 27610021
TI - Comparative effects of alpha2delta-1 ligands in mouse models of colonic
hypersensitivity.
AB - AIM: To investigate anti-hypersensitive effects of alpha2delta-1 ligands in non
inflammatory and inflammation-associated colonic hypersensitivity (CHS) mouse
models. METHODS: To induce an inflammation-associated CHS, 1% dextran sulfate
sodium (DSS) was administered to C57Bl/6J male mice, in drinking water, for 14 d.
Regarding the non-inflammatory neonatal maternal separation (NMS) -induced CHS
model, wild-type C57BI/6J pups were isolated from their mother from day 2 to day
14 (P2 to P14), three hours per day (from 9:00 a.m. to 12:00 p.m.). Colorectal
distension was performed by inflating distension probe from 20 MUL to 100 MUL by
20 MUL increment step every 10 s. After a first colorectal distension (CRD),
drugs were administered subcutaneously, in a cumulative manner, (Gabapentin at 30
mg/kg and 100 mg/kg; Pregabalin at 10 mg/kg and 30 mg/kg; Carbamazepine at 10
mg/kg and 30 mg/kg) and a second CRD was performed one hour after each injection.
RESULTS: The visceromotor response (VMR) to CRD was increased by our NMS paradigm
protocol in comparison to non-handled (NH) mice, considering the highest
distension volumes (80 MUL: 0.783 +/- 0.056 mV/s vs 0.531 +/- 0.034 mV/s, P <
0.05 and 100 MUL: 1.087 +/- 0.056 mV/s vs 0.634 +/- 0.038 mV/s, P < 0.05 for NMS
and NH mice, respectively). In the inflammation-associated CHS, DSS-treated mice
showed a dramatic and significant increase in VMR at 60 and 80 MUL distension
volumes when compared to control mice (60 MUL: 0.920 +/- 0.079 mV/s vs 0.426 +/-
0.100 mV/s P < 0.05 and 80 MUL: 1.193 +/- 0.097 mV/s vs 0.681 +/- 0.094 mV/s P <
0.05 for DSS- and Water-treated mice, respectively). Carbamazepine failed to
significantly reduce CHS in both models. Gabapentin significantly reduced CHS in
the DSS-induced model for both subcutaneous injections at 30 or 100 mg/kg.
Pregabalin significantly reduced VMR to CRD in the non-inflammatory NMS-induced
CHS model for the acute subcutaneous administration of the highest cumulative
dose (30 mg/kg) and significantly reduced CHS in low-dose DSS-treated mice in a
dose-dependent manner. Finally, the percent decrease of AUC induced by acute GBP
or Pregabalin treatment were higher in the inflammatory DSS-induced CHS model in
comparison to the non-inflammatory NMS-induced CHS model. CONCLUSION: This
preclinical study demonstrates alpha2delta-1 ligands efficacy on inflammation
associated CHS, highlighting their potential clinical interest in patients with
chronic abdominal pain and moderate intestinal inflammation.
PMID- 27610022
TI - Computer-aided texture analysis combined with experts' knowledge: Improving
endoscopic celiac disease diagnosis.
AB - AIM: To further improve the endoscopic detection of intestinal mucosa alterations
due to celiac disease (CD). METHODS: We assessed a hybrid approach based on the
integration of expert knowledge into the computer-based classification pipeline.
A total of 2835 endoscopic images from the duodenum were recorded in 290 children
using the modified immersion technique (MIT). These children underwent routine
upper endoscopy for suspected CD or non-celiac upper abdominal symptoms between
August 2008 and December 2014. Blinded to the clinical data and biopsy results,
three medical experts visually classified each image as normal mucosa (Marsh-0)
or villous atrophy (Marsh-3). The experts' decisions were further integrated into
state-of-the-art texture recognition systems. Using the biopsy results as the
reference standard, the classification accuracies of this hybrid approach were
compared to the experts' diagnoses in 27 different settings. RESULTS: Compared to
the experts' diagnoses, in 24 of 27 classification settings (consisting of three
imaging modalities, three endoscopists and three classification approaches), the
best overall classification accuracies were obtained with the new hybrid
approach. In 17 of 24 classification settings, the improvements achieved with the
hybrid approach were statistically significant (P < 0.05). Using the hybrid
approach classification accuracies between 94% and 100% were obtained. Whereas
the improvements are only moderate in the case of the most experienced expert,
the results of the less experienced expert could be improved significantly in 17
out of 18 classification settings. Furthermore, the lowest classification
accuracy, based on the combination of one database and one specific expert, could
be improved from 80% to 95% (P < 0.001). CONCLUSION: The overall classification
performance of medical experts, especially less experienced experts, can be
boosted significantly by integrating expert knowledge into computer-aided
diagnosis systems.
PMID- 27610023
TI - Development of a human rotavirus induced diarrhea model in Chinese mini-pigs.
AB - AIM: To establish a new animal model for the research of human rotavirus (HRV)
infection, its pathogenesis and immunity and evaluation of potential vaccines.
METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and Bamma, were
inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and
PBS (control), respectively, and fecal samples of pigs from 0 to 7 d post
infection (DPI) were collected individually. Enzyme linked immunosorbent assay
was used to detect HRV antigen in feces. The HRV was tested by real-time PCR (RT
PCR). The sections of the intestinal tissue were stained with hematoxylin and
eosin to observe the morphologic variation by microscopy. Immunofluorescence was
used to determine the HRV in intestinal tissue. HRV particles in cells of the
ileum were observed by electron micrography. RESULTS: When inoculated with HRV,
mini-pigs younger than 30 d developed diarrhea in an age-dependent manner and
shed HRV antigen of the same inoculum, as demonstrated by RT-PCR.
Histopathological changes were observed in HRV inoculated mini-pigs including
small intestinal cell tumefaction and necrosis. HRV that was distributed in the
small intestine was restricted to the top part of the villi on the internal wall
of the ileum, which was observed by immunofluorescence and transmission electron
microscopy. Virus particles were observed in Golgi like follicles in HRV-infected
neonatal mini-pigs. Guizhou mini-pigs were more sensitive to HRV than Bamma with
respect to RV antigen shedding and clinical diarrhea. CONCLUSION: These results
indicate that we have established a mini-pig model of HRV induced diarrhea. Our
findings are useful for the understanding of the pathogenic mechanisms of HRV
infection.
PMID- 27610024
TI - Nicotinic cholinergic receptors in esophagus: Early alteration during
carcinogenesis and prognostic value.
AB - AIM: To compare expression of nicotinic cholinergic receptors (CHRNs) in healthy
and squamous cell carcinoma-affected esophagus and determine the prognostic
value. METHODS: We performed RT-qPCR to measure the expression of CHRNs in 44
esophageal samples from healthy individuals and in matched normal surrounding
mucosa, and in tumors from 28 patients diagnosed with esophageal squamous cell
carcinoma (ESCC). Next, we performed correlation analysis for the detected
expression of these receptors with the habits and clinico-pathological
characteristics of all study participants. In order to investigate the possible
correlations between the expression of the different CHRN subunits in both
healthy esophagus and tissues from ESCC patients, correlation matrices were
generated. Subsequently, we evaluated whether the detected alterations in
expression of the various CHRNs could precede histopathological modifications
during the esophageal carcinogenic processes by using receiver operating
characteristic curve analysis. Finally, we evaluated the impact of CHRNA5 and
CHRNA7 expression on overall survival by using multivariate analysis. RESULTS:
CHRNA3, CHRNA5, CHRNA7 and CHRNB4, but not CHRNA1, CHRNA4, CHRNA9 or CHRNA10,
were found to be expressed in normal (healthy) esophageal mucosa. In ESCC, CHRNA5
and CHRNA7 were overexpressed as compared with patient-matched surrounding non
tumor mucosa (ESCC-adjacent mucosa; P < 0.0001 and P = 0.0091, respectively).
Positive correlations were observed between CHRNA3 and CHRNB4 expression in all
samples analyzed. Additionally, CHRNB4 was found to be differentially expressed
in the healthy esophagus and the normal-appearing ESCC-adjacent mucosa, allowing
for distinguishment between these tissues with a sensitivity of 75.86% and a
specificity of 78.95% (P = 0.0002). Finally, CHRNA5 expression was identified as
an independent prognostic factor in ESCC; patients with high CHRNA5 expression
showed an increased overall survival, in comparison with those with low
expression. The corresponding age- and tumor stage-adjusted hazard ratio was
0.2684 (95%CI: 0.075-0.97, P = 0.0448). CONCLUSION: Expression of CHRNs is
homogeneous along healthy esophagus and deregulated in ESCC, suggesting a
pathogenic role for these receptors in ESCC development and progression.
PMID- 27610025
TI - Prognostic significance of computed tomography-detected extramural vascular
invasion in colon cancer.
AB - AIM: To compare disease-free survival (DFS) between extramural vascular invasion
(EMVI)-positive and -negative colon cancer patients evaluated by computed
tomography (CT). METHODS: Colon cancer patients (n = 194) undergoing curative
surgery between January 2009 and December 2013 were included. Each patient's
demographics, cancer characteristics, EMVI status, pathological status and
survival outcomes were recorded. All included patients had been routinely
monitored until December 2015. EMVI was defined as tumor tissue within adjacent
vessels beyond the colon wall as seen on enhanced CT. Disease recurrence was
defined as metachronous metastases, local recurrence, or death due to colon
cancer. Kaplan-Meier analyses were used to compare DFS between the EMVI-positive
and -negative groups. Cox's proportional hazards models were used to measure the
impact of confounding variables on survival rates. RESULTS: EMVI was observed on
CT (ctEMVI) in 60 patients (30.9%, 60/194). One year after surgery, there was no
statistically significant difference regarding the rates of progressive events
between EMVI-positive and -negative patients [11.7% (7/60) and 6.7% (9/134),
respectively; P = 0.266]. At the study endpoint, the EMVI-positive patients had
significantly more progressive events than the EMVI-negative patients [43.3%
(26/60) and 14.9% (20/134), respectively; odds ratio = 4.4, P < 0.001]. Based on
the Kaplan-Meier method, the cumulative 1-year DFS rates were 86.7% (95%CI: 82.3
91.1) and 92.4% (95%CI: 90.1-94.7) for EMVI-positive and EMVI-negative patients,
respectively. The cumulative 3-year DFS rates were 49.5% (95%CI: 42.1-56.9) and
85.8% (95%CI: 82.6-89.0), respectively. Cox proportional hazards regression
analysis revealed that ctEMVI was an independent predictor of DFS with a hazard
ratio of 2.15 (95%CI: 1.12-4.14, P = 0.023). CONCLUSION: ctEMVI may be helpful
when evaluating disease progression in colon cancer patients.
PMID- 27610026
TI - Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and
literature review.
AB - Involvement of gastrointestinal tract by cytomegalovirus (CMV) is common. CMV
infections mainly run their course without any clinical signs in immunocompetent
hosts. In contrast, CMV can cause severe infections with serious consequences in
a immunocompromised state typically associated with organ transplants, highly
immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with
corticosteroids. The incidence and severity of these manifestations of CMV is
directly proportional with the degree of cellular immune dysfunction, i.e., CD8+
Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in
different situations including reactivation of CMV from latency, primary
infection in a seronegative host, or exposure of a seropositive host to a new
strain of CMV. As the clinical signs of CMV in immunodeficient patients are
usually sparse, physicians should be highly vigilant about CMV infection, a
treatable condition that otherwise is associated with significant mortality. Here
we report a rare case of severe gastrointestinal CMV infection with sustained
immunodeficiency secondary to treatment with steroids manifesting as fatal
duodenal diverticular bleeding.
PMID- 27610027
TI - Associations of Physical Activity and Sedentary Behavior With Adolescent Academic
Achievement.
AB - The Northern Finland Birth Cohort 1986 (N = 8,061) was used to investigated the
joint associations of physical activity and sedentary behavior with academic
achievement. Logistic regression analysis was used to evaluate how classes formed
by latent class analysis (LCA) according to overall physical activity, sports
club membership, viewing TV, using a computer, reading books and magazines, other
sedentary activities, and sleep were associated with grade-point average. When
adjusted for gender, self-rated health, and mother's education, physically active
adolescents and generally active adolescents were about twice as likely to have
high grade-point average compared with sedentary TV viewers.
PMID- 27610028
TI - Respiratory Presentation of Pediatric Patients in the 2014 Enterovirus D68
Outbreak.
AB - Background. In the fall of 2014, a North American outbreak of enterovirus D68
resulted in a significant number of pediatric hospital admissions for respiratory
illness throughout North America. This study characterized the clinical
presentation and risk factors for a severe clinical course in children admitted
to British Columbia Children's Hospital during the 2014 outbreak. Methods.
Retrospective chart review of patients with confirmed EV-D68 infection admitted
to BCCH with respiratory symptoms in the fall of 2014. Past medical history,
clinical presentation, management, and course in hospital was collected and
analyzed using descriptive statistics. Comparison was made between those that did
and did not require ICU admission to identify risk factors. Results. Thirty-four
patients were included (median age 7.5 years). Fifty-three percent of children
had a prior history of wheeze, 32% had other preexisting medical comorbidities,
and 15% were previously healthy. Ten children (29%) were admitted to the
pediatric intensive care unit. The presence of complex medical conditions
(excluding wheezing) (P = 0.03) and copathogens was associated with PICU
admission (P = 0.02). Conclusions. EV-D68 infection resulted in severe, prolonged
presentations of asthma-like illness in the hospitalized pediatric population.
Patients with a prior history of wheeze and preexisting medical comorbidities
appear to be most severely affected, but the virus can also cause wheezing in
previously well children.
PMID- 27610029
TI - The Development of a Critical Care Resident Research Curriculum: A Needs
Assessment.
AB - Background. Conducting research is expected from many clinicians' professional
profile, yet many do not have advanced research degrees. Research training during
residency is variable amongst institutions and research education needs of
trainees are not well understood. Objective. To understand needs of critical care
trainees regarding research education. Methods. Canadian critical care trainees,
new critical care faculty, program directors, and research coordinators were
surveyed regarding research training, research expectations, and support within
their programs. Results. Critical care trainees and junior faculty members
highlighted many gaps in research knowledge and skills. In contrast, critical
care program directors felt that trainees were prepared to undertake research
careers. Major differences in opinion amongst program directors and other
respondent groups exist regarding preparation for designing a study, navigating
research ethics board applications, and managing a research budget. Conclusion.
We demonstrated that Canadian critical care trainees and junior faculty reported
gaps in knowledge in all areas of research. There was disagreement amongst
trainees, junior faculty, research coordinators, and program directors regarding
learning needs. Results from this needs assessment will be used to help redesign
the education program of the Canadian Critical Care Trials Group to complement
local research training offered for critical care trainees.
PMID- 27610030
TI - Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric
oxide synthase.
AB - Despite the complex vascular effects of dexmedetomidine (DEX), its actions on
human pulmonary resistance arteries remain unknown. The present study tested the
hypothesis that DEX inhibits vascular tension in human pulmonary arteries through
the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide
(NO). Pulmonary artery segments were obtained from 62 patients who underwent lung
resection. The direct effects of DEX on human pulmonary artery tension and
changes in vascular tension were determined by isometric force measurements
recorded on a myograph. Arterial contractions caused by increasing concentrations
of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric
oxide synthase inhibitor), yohimbine (alpha2-adrenoceptor antagonist) and
indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX
had no effect on endothelium-intact pulmonary arteries, whereas at concentrations
of 10(-8)~10(-6) mol/L, it elicited contractions in endothelium-denuded pulmonary
arteries. DEX (0.3, 1, or 3*10(-9) mmol/L) inhibited serotonin-induced
contraction in arteries with intact endothelium in a dose-dependent manner. L
NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no
effect. No inhibitory effect was observed in endothelium-denuded pulmonary
arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries
is mediated by NO production induced by the activation of endothelial alpha2
adrenoceptor and nitric oxide synthase.
PMID- 27610031
TI - N-acetyl-L-cysteine and cysteine increase intracellular calcium concentration in
human neutrophils.
AB - N-acetyl-L-cysteine (NAC) and cysteine have been implicated in a number of human
neutrophils' functional responses. However, though Ca(2+) signaling is one of the
key signalings contributing to the functional responses of human neutrophils,
effects of NAC and cysteine on intracellular calcium concentration ([Ca(2+)]i) in
human neutrophils have not been investigated yet. Thus, this study was carried
out with an objective to investigate the effects of NAC and cysteine on [Ca(2+)]i
in human neutrophils. We observed that NAC (1 uM ~ 1 mM) and cysteine (10 uM ~ 1
mM) increased [Ca(2+)]i in human neutrophils in a concentration-dependent manner.
In NAC pre-supplmented buffer, an additive effect on N-formyl-methionine-leucine
phenylalanine (fMLP)-induced increase in [Ca(2+)]i in human neutrophils was
observed. In Ca(2+)-free buffer, NAC- and cysteine-induced [Ca(2+)]i increase in
human neutrophils completely disappeared, suggesting that NAC- and cysteine
mediated increase in [Ca(2+)]i in human neutrophils occur through Ca(2+) influx.
NAC- and cysteine-induced [Ca(2+)]i increase was effectively inhibited by calcium
channel inhibitors SKF96365 (10 uM) and ruthenium red (20 uM). In Na(+)-free
HEPES, both NAC and cysteine induced a marked increase in [Ca(2+)]i in human
neutrophils, arguing against the possibility that Na(+)-dependent intracellular
uptake of NAC and cysteine is necessary for their [Ca(2+)]i increasing activity.
Our results show that NAC and cysteine induce [Ca(2+)]i increase through Ca(2+)
influx in human neutrophils via SKF96365- and ruthenium red-dependent way.
PMID- 27610032
TI - Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome
proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal
stem cells.
AB - Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for
metabolic homeostasis and nutrient signaling during development. However, limited
information is available on the pivotal modulators of adipogenic differentiation
of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a
family of SH2-containing proteins, modulates the bioactivities of different stem
cells, including hematopoietic stem cells and endothelial progenitor cells. In
this study, we investigated whether an interaction between insulin-like growth
factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic
differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic
differentiation potential than Lnk (-/-) MSCs. An ex vivo adipogenic
differentiation assay showed that Lnk (-/-) MSCs had decreased adipogenic
differentiation potential compared with wild-type MSCs. Interestingly, we found
that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of
this complex. In addition, we observed that IGF-1-induced increase in the
phosphorylation of Akt and mammalian target of rapamycin was triggered by the
dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal
transcription factor peroxisome proliferator-activated receptor gamma (PPAR
gamma) and its adipogenic target genes (LPL and FABP4) significantly decreased in
Lnk (-/-) MSCs. These results suggested that Lnk adaptor protein regulated the
adipogenesis of MSCs through the IGF-1/Akt/PPAR-gamma pathway.
PMID- 27610033
TI - Effect of pertussis toxin pretreated centrally on blood glucose level induced by
stress.
AB - In the present study, we examined the effect of pertussis toxin (PTX)
administered centrally in a variety of stress-induced blood glucose level. Mice
were exposed to stress after the pretreatment of PTX (0.05 or 0.1 ug) i.c.v. or
i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min
after stress stimulation. The blood glucose level was increased in all stress
groups. The blood glucose level reached at maximum level after 30 min of stress
stimulation and returned to a normal level after 2 h of stress stimulation in
restraint stress, physical, and emotional stress groups. The blood glucose level
induced by cold-water swimming stress was gradually increased up to 1 h and
returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal
(i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and
almost abolished the elevation of the blood level induced by stress stimulation.
The central pretreatment with PTX caused a reduction of plasma insulin level,
whereas plasma corticosterone level was further up-regulated in all stress
models. Our results suggest that the hyperglycemia produced by physical stress,
emotional stress, restraint stress, and the cold-water swimming stress appear to
be mediated by activation of centrally located PTX-sensitive G proteins. The
reduction of blood glucose level by PTX appears to due to the reduction of plasma
insulin level. The reduction of blood glucose level by PTX was accompanied by the
reduction of plasma insulin level. Plasma corticosterone level up-regulation by
PTX in stress models may be due to a blood glucose homeostatic mechanism.
PMID- 27610034
TI - Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and
fibrosis in DOCA-induced hypertensive rats.
AB - CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially
developed for treatment of various hematological and solid cancers. Because it is
water-soluble, it can be administered orally. We hypothesized that the HDAC
inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in
deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment
of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly
into Sprague-Dawley rats. All the rats used in this study including those in the
sham group had been unilaterally nephrectomized and allowed free access to
drinking water containing 1% NaCl. Systolic blood pressure was measured by the
tail-cuff method. Blood chemistry including sodium, potassium, glucose,
triglyceride, and cholesterol levels was analyzed. Sections of the heart were
visualized after trichrome and hematoxylin and eosin stain. The expression of
hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial
natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1,
Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured
by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic
blood pressure, heart weight, and cardiac fibrosis, which was attenuated by
CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction
and relaxation responses, and blood chemistry. Injection of DOCA increased
expression of both hypertrophic and fibrotic genes, which was abrogated by
CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and
fibrosis in DOCA-induced hypertensive rats.
PMID- 27610035
TI - p53 signaling is involved in leptin-induced growth of hepatic and breast cancer
cells.
AB - Leptin, an adipokine predominantly produced from adipose tissue, is well known to
induce tumor growth. However, underlying molecular mechanisms are not established
yet. While p53 has long been well recognized as a potent tumor suppressor gene,
accumulating evidence has also indicated its potential role in growth and
survival of cancer cells depending on experimental environments. In the present
study, we examined if p53 signaling is implicated in leptin-induced growth of
cancer cells. Herein, we demonstrated that leptin treatment significantly
increased p53 protein expression in both hepatic (HepG2) and breast (MCF-7)
cancer cells without significant effect on mRNA expression. Enhanced p53
expression by leptin was mediated via modulation of ubiquitination, in particular
ubiquitin specific protease 2 (USP2)-dependent manner. Furthermore, gene
silencing of p53 by small interfering RNA (siRNA) suppressed leptin-induced
growth of hepatic and breast cancer cells, indicating the role of p53 signaling
in tumor growth by leptin. In addition, we also showed that knockdown of p53
restored suppression of caspase-3 activity by leptin through modulating Bax
expression and prevented leptin-induced cell cycle progression, implying the
involvement of p53 signaling in the regulation of both apoptosis and cell cycle
progression in cancer cells treated with leptin. Taken together, the results in
the present study demonstrated the potential role of p53 signaling in leptin
induced tumor growth.
PMID- 27610036
TI - Seasonal acclimation in sudomotor function evaluated by QSART in healthy humans.
AB - The quantitative sudomotor axon reflex testing (QSART) is a classic test of
routine postganglionic sudomotor function. We investigated sudomotor function by
QSART after summer (July 2012) and winter (January 2013) seasonal acclimation
(SA) in the Republic of Korea. QSART with acetylcholine (ACh) iontophoresis were
performed to determine directly activated (DIR) and axon reflex-mediated (AXR1,
2) sweating rate. Onset time of axon reflex, activated sweat gland density
(ASGD), activated sweat gland output (ASGO), tympanic and skin temperatures (Tty,
Tsk), basal metabolic rate (BMR), and evaporative loss volume changes were
measured. Tympanic and mean body temperature (Tb; calculated from Tty, Tsk) were
significantly lower after summer-SA than that of winter-SA. Sweat onset time was
delayed during winter-SA compared to that after summer-SA. BMR, AXR(1), AXR(2),
and DIR sweat rates, ASGD and ASGO, and evaporative loss volume were
significantly diminished after winter-SA relative to after summer-SA. In
conclusion, changes in sweating activity measured by QSART confirmed the
involvement of the peripheral nervous system in variation of sudomotor activity
in seasonal acclimation.
PMID- 27610037
TI - Spatial reproducibility of complex fractionated atrial electrogram depending on
the direction and configuration of bipolar electrodes: an in-silico modeling
study.
AB - Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in
radiofrequency catheter ablation for persistent atrial fibrillation (AF), the
directions and configuration of the bipolar electrodes may affect the
electrogram. This study aimed to compare the spatial reproducibility of CFAE by
changing the catheter orientations and electrode distance in an in-silico left
atrium (LA). We conducted this study by importing the heart CT image of a patient
with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle
lengths (CLs) were compared for 16 different orientations of a virtual bipolar
conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm).
Additionally, the spatial correlations of CFAE-CLs and the percentage of
consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv
cath were compared with that obtained using a mini catheter (mini-cath: size 1
mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the
electrogram morphology and CFAE-CLs varied (conv-cath: 11.5+/-0.7% variation,
mini-cath: 7.1+/-1.2% variation), however the mini-cath produced less variation
of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations
among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055+/-0.2194 vs. mini
cath: 0.6074+/-0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites
was higher for mini catheter than conventional one (38.3+/-4.6% vs. 22.3+/-1.4%,
p<0.05). Electrograms and CFAE distribution are affected by catheter orientation
and electrode configuration in the in-silico LA model. However, there was
moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters
were less influenced by catheter direction than conventional catheters.
PMID- 27610039
TI - DAMGO modulates two-pore domain K(+) channels in the substantia gelatinosa
neurons of rat spinal cord.
AB - The analgesic mechanism of opioids is known to decrease the excitability of
substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary
nociceptive afferent fiber by increasing inwardly rectifying K(+) current. In
this study, we examined whether a u-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]
enkephalin (DAMGO), affects the two-pore domain K(+) channel (K2P) current in rat
SG neurons using a slice whole-cell patch clamp technique. Also we confirmed
which subtypes of K2P channels were associated with DAMGO-induced currents,
measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO
caused a robust hyperpolarization and outward current in the SG neurons, which
developed almost instantaneously and did not show any time-dependent
inactivation. Half of the SG neurons exhibited a linear I~V relationship of the
DAMGO-induced current, whereas rest of the neurons displayed inward
rectification. In SG neurons with a linear I~V relationship of DAMGO-induced
current, the reversal potential was close to the K(+) equilibrium potentials. The
mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying
K(+) channel) related acid-sensitive K(+) channel (TASK) 1 and 3 was found in the
SG region and a low pH (6.4) significantly blocked the DAMGO-induced K(+)
current. Taken together, the DAMGO-induced hyperpolarization at resting membrane
potential and subsequent decrease in excitability of SG neurons can be carried by
the two-pore domain K(+) channel (TASK1 and 3) in addition to inwardly rectifying
K(+) channel.
PMID- 27610038
TI - Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937
cell adhesion.
AB - Adhesion events of monocytes represent an important step in inflammatory
responses induced by chemokines. The beta1-integrin CD29 is a major adhesion
molecule regulating leukocyte migration and extravasation. Although several
adhesion molecules have been known as regulators of CD29, the molecular
interactions between CD29 and its regulatory adhesion molecules (such as CD98 and
CD147) have not been fully elucidated. Therefore, in this study, we examined
whether these molecules are functionally, biochemically, and cell-biologically
associated using monocytic U937 cells treated with aggregation-stimulating and
blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29,
CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of
CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies
triggered the induction of cell-cell adhesion, and sensitivity to various enzyme
inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and
CD147-induced U937 cell aggregation. Molecular association between these
molecules and the actin cytoskeleton was confirmed by confocal microscopy and
immunoprecipitation. These results strongly suggest that CD29 might be modulated
by its biochemical and cellular regulators, including CD98 and CD147, via the
actin cytoskeleton.
PMID- 27610040
TI - Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling
pathway.
AB - Angiogenesis plays an essential role in embryo development, tissue repair,
inflammatory diseases, and tumor growth. In the present study, we showed that
endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice
that lack eNOS showed growth retardation, and retinal vessel development was
significantly delayed. In addition, the number of tip cells and filopodia length
were significantly reduced in mice lacking eNOS. Retinal endothelial cell
proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced
endothelial cell sprouting was significantly reduced in aortic vessels isolated
from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and
vascular smooth muscle cell coverage to blood vessels were attenuated in mice
lacking eNOS. Taken together, we suggest that the endothelial cell function and
blood vessel maturation are regulated by eNOS during retinal angiogenesis.
PMID- 27610041
TI - Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt
eNOS dependent pathway.
AB - Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has
anticoagulant and anti-inflammatory properties. The intracellular mediator and
external anti-inflammatory external signal in the vascular wall have been
reported to protect endothelial cells, in part due to nitric oxide (NO)
production. This study was designed to examine whether NM exhibit endothelium
dependent vascular relaxation through Akt/endothelial nitric oxide synthase
(eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and
NO production in a dose- and time-dependent manner in human umbilical vein
endothelial cells (HUVECs) and aorta tissues obtained from rats treated with
various concentrations of NM. NM concomitantly decreased arginase activity, which
could increase the available arginine substrate for NO production. Moreover, we
investigated whether NM increased NO bioavailability and decreased aortic
relaxation response to an eNOS inhibitor in the aorta. These results suggest that
NM increases NO generation via the Akt/eNOS signaling pathway, leading to
endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of
NM may contribute to the regulation of cardiovascular function.
PMID- 27610042
TI - Myometrial relaxation of mice via expression of two pore domain acid sensitive
K(+) (TASK-2) channels.
AB - Myometrial relaxation of mouse via expression of two-pore domain acid sensitive
(TASK) channels was studied. In our previous report, we suggested that two-pore
domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the
regulation of uterine circular smooth muscles in mice. In this study, we tried to
show the mechanisms of relaxation via TASK-2 channels in marine myometrium.
Isometric contraction measurements and patch clamp technique were used to verify
TASK conductance in murine myometrium. Western blot and immunehistochemical study
under confocal microscopy were used to investigate molecular identity of TASK
channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating
outward K(+) current (NIOK) may be responsible for the quiescence of murine
pregnant longitudinal myometrium. The characteristics of NIOK coincided with two
pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+)
channel blockers was inhibited further by TASK inhibitors such as quinidine,
bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and
estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant
myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine
and increased immunohistochemical expression of TASK-2. Finally, TASK-2
inhibitors induced strong myometrial contraction even in the presence of L
methionine, a known inhibitor of stretch-activated channels in the longitudinal
myometrium of mouse. Activation of TASK-2 channels seems to play an essential
role for relaxing uterus during pregnancy and it might be one of the alternatives
for preventing preterm delivery.
PMID- 27610043
TI - Detection of Mycobacterium ulcerans by real-time PCR with improved primers.
AB - BACKGROUND: Buruli ulcer is a severe skin disease caused by Mycobacterium
ulcerans. Real-time PCR targeting the IS2404 sequence has been used as a reliable
and rapid method for the diagnosis of Buruli ulcer and detection of M. ulcerans
in the environment. The genome of M. ulcerans contains hundreds of IS2404 copies,
which have variability in certain sequences. Therefore, the design of new primers
specific to conserved IS2404 regions may potentially improve the sensitivity of
M. ulcerans detection and, consequently, the diagnosis of Buruli ulcer, thus
ensuring timely treatment of the disease. RESULTS: In silico analysis indicates
that DNA sequences of the IS2404 elements are highly variable within a single
strain. As the binding sites of conventional IS2404-specific primers used for M.
ulcerans detection contain polymorphic sequences, we designed new primers, which
enabled the detection of M. ulcerans by real-time PCR with higher sensitivity and
similar specificity with respect to that of conventional primers. However, the
increase in sensitivity with the new primers depended on the M. ulcerans strain.
CONCLUSIONS: The results suggest that real-time PCR based on the new primers
could improve Buruli ulcer diagnosis and M. ulcerans detection in environmental
samples.
PMID- 27610044
TI - Selected polyphenols potentiate the apoptotic efficacy of glycolytic inhibitors
in human acute myeloid leukemia cell lines. Regulation by protein kinase
activities.
AB - BACKGROUND: The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) is a safe,
potentially useful anti-tumour drug, but its efficacy is normally low when used
alone. Recent studies indicated that 2-DG stimulates the PI3K/Akt and MEK/ERK
defensive pathways, which limits the apoptotic efficacy in tumour cell lines. We
hypothesized that co-treatment with selected polyphenols could improve 2-DG
provoked apoptosis by preventing defensive kinase activation. METHODS: Cell
proliferation was measured by cell counting or the MTT assay. Cell cycle,
apoptosis and necrosis were determined by propidium iodide staining and/or
annexin V labeling followed by flow cytometry. Mitochondria pore transition and
depolarization were determined by calcein-ATM or rhodamine 123 labeling followed
flow cytometry. Intracellular reactive oxygen species and GSH were determined by
dichlorodihydrofluorescein diacetate or monochlorobimane labeling followed by
flow cytometry or fluorimetry. Expression and phosphorylation of protein kinases
were analyzed by the Western blot. RESULTS: (i) 2-DG-provoked apoptosis was
greatly potentiated by co-treatment with the sub-lethal concentrations of the
flavonoid quercetin in human HL60 acute myeloblastic leukemia cells. Allowing for
quantitative differences, apoptosis potentiation was also obtained using NB4
promyelocytic and THP-1 promonocytic cells, using curcumin or genistein instead
of quercetin, and using lonidamine instead of 2-DG, but not when 2-DG was
substituted by incubation in glucose-free medium. (ii) Quercetin and 2-DG rapidly
elicited the opening of mitochondria pore transition, which preceded the trigger
of apoptosis. (iii) Treatments did not affect GSH levels, and caused disparate
effects on reactive oxygen species generation, which did not match the changes in
lethality. (iv) 2-DG and lonidamine stimulated defensive Akt and ERK
phosphorylation/activation, while glucose starvation was ineffective. Polyphenols
prevented the stimulation of Akt phosphorylation, and in some cases also ERK
phosphorylation. In addition, quercetin and 2-DG stimulated GSK-3alpha,beta
phosphorylation/inactivation, although with different isoform specificity. The
use of pharmacologic inhibitors confirmed the importance of these kinase
modifications for apoptosis. CONCLUSIONS: The present in vitro observations
suggest that co-treatment with low concentrations of selected polyphenols might
represent a manner of improving the poor anti-tumour efficacy of some glycolytic
inhibitors, and that apoptosis potentiation may be at least in part explained by
the regulation of defensive protein kinase activities.
PMID- 27610046
TI - Comparative proteomic analyses of Asian cotton ovules with attached fibers in the
early stages of fiber elongation process.
AB - BACKGROUND: Plenty of proteomic studies were performed to characterize the
allotetraploid upland cotton fiber elongation process, whereas little is known
about the elongating diploid cotton fiber proteome. METHODS: In this study, we
used a two-dimensional electrophoresis-based comparative proteomic approach to
profile dynamic proteomes of diploid Asian cotton ovules with attached fibers in
the early stages of fiber elongation process. One-way ANOVA and Student-Newman
Keuls test were used to find the differentially displayed protein (DDP) spots.
RESULTS: A total of 55 protein spots were found having different abundance
ranging from 1 to 9 days post-anthesis (DPA) in a two-day interval. These 55 DDP
spots were all successfully identified using high-resolution mass spectrometric
analyses. Gene ontology analyses revealed that proteoforms involved in
energy/carbohydrate metabolism, redox homeostasis, and protein metabolism are the
most abundant. In addition, orthologues of the 13 DDP spots were also found in
differential proteome of allotetraploid elongating cotton fibers, suggesting
their possible essential roles in fiber elongation process. CONCLUSIONS: Our
results not only revealed the dynamic proteome change of diploid Asian cotton
fiber and ovule during early stages of fiber elongation process but also provided
valuable resource for future studies on the molecular mechanism how the
polyploidization improves the trait of fiber length.
PMID- 27610047
TI - Barista: A Framework for Concurrent Speech Processing by USC-SAIL.
AB - We present Barista, an open-source framework for concurrent speech processing
based on the Kaldi speech recognition toolkit and the libcppa actor library. With
Barista, we aim to provide an easy-to-use, extensible framework for constructing
highly customizable concurrent (and/or distributed) networks for a variety of
speech processing tasks. Each Barista network specifies a flow of data between
simple actors, concurrent entities communicating by message passing, modeled
after Kaldi tools. Leveraging the fast and reliable concurrency and distribution
mechanisms provided by libcppa, Barista lets demanding speech processing tasks,
such as real-time speech recognizers and complex training workflows, to be
scheduled and executed on parallel (and/or distributed) hardware. Barista is
released under the Apache License v2.0.
PMID- 27610045
TI - Identifying EGFR mutation-induced drug resistance based on alpha shape model
analysis of the dynamics.
AB - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation-induced drug
resistance is a difficult problem in lung cancer treatment. Studying the
molecular mechanisms of drug resistance can help to develop corresponding
treatment strategies and benefit new drug design. METHODS: In this study, Rosetta
was employed to model the EGFR mutant structures. Then Amber was carried out to
conduct molecular dynamics (MD) simulation. Afterwards, we used Computational
Geometry Algorithms Library (CGAL) to compute the alpha shape model of the
mutants. RESULTS: We analyzed the EGFR mutation-induced drug resistance based on
the motion trajectories obtained from MD simulation. We computed alpha shape
model of all the trajectory frames for each mutation type. Solid angle was used
to characterize the curvature of the atoms at the drug binding site. We measured
the knob level of the drug binding pocket of each mutant from two ways and
analyzed its relationship with the drug response level. Results show that 90 % of
the mutants can be grouped correctly by setting a certain knob level threshold.
CONCLUSIONS: There is a strong correlation between the geometric properties of
the drug binding pocket of the EGFR mutants and the corresponding drug responses,
which can be used to predict the response of a new EGFR mutant to a drug
molecule.
PMID- 27610049
TI - Combined uncertainty estimation for the determination of the dissolved iron
amount content in seawater using flow injection with chemiluminescence detection.
AB - This work assesses the components contributing to the combined uncertainty budget
associated with the measurement of the Fe amount content by flow injection
chemiluminescence (FI-CL) in <0.2 MUm filtered and acidified seawater samples.
Amounts of loaded standard solutions and samples were determined gravimetrically
by differential weighing. Up to 5% variations in the loaded masses were observed
during measurements, in contradiction to the usual assumptions made when
operating under constant loading time conditions. Hence signal intensities (V)
were normalised to the loaded mass and plots of average normalised intensities
(in V kg-1) vs. values of the Fe amount content (in nmol kg-1) added to a "low
level" iron seawater matrix were used to produce the calibration graphs. The
measurement procedure implemented and the uncertainty estimation process
developed were validated from the agreement obtained with consensus values for
three SAFe and GEOTRACES reference materials (D2, GS, and GD). Relative expanded
uncertainties for peak height and peak area based results were estimated to be
around 12% and 10% (coverage factor k = 2), respectively. The most important
contributory factors were the uncertainty on the sensitivity coefficient (i.e.,
calibration slope) and the within-sequence-stability (i.e., the signal stability
over several hours of operation; here 32 h). For GD, using peak height
measurements, these factors contributed respectively 69.7% and 21.6% while the
short-term repeatability accounted for only 7.9%. Therefore, an uncertainty
estimation based on the intensity repeatability alone, as is often done in FI-CL
studies, is not a realistic estimation of the overall uncertainty of the
procedure.
PMID- 27610048
TI - Challenges Associated With Managing Suicide Risk in Long-Term Care Facilities.
AB - Little information about suicidal ideation and behavior in long-term care (LTC)
facilities is available. Nonetheless, the implementation of the Minimum Data Set
3.0 requires that LTC facilities screen their residents for suicide risk and have
protocols in place to effectively manage residents' responses. In this article,
the authors briefly discuss the risk factors of suicide in the elderly and the
problems that suicidal ideation and behavior pose in the LTC environment. The
authors explain issues that arise when trying to manage suicide risk in the
elderly LTC population with general, traditional approaches. These inherent
issues make it difficult to develop an effective protocol for managing suicide
risk in LTC facilities, leading the authors to propose their own framework for
assessing and managing suicide risk in the LTC setting.
PMID- 27610051
TI - A review of recent advances in the spherical harmonics expansion method for
semiconductor device simulation.
AB - The Boltzmann transport equation is commonly considered to be the best semi
classical description of carrier transport in semiconductors, providing precise
information about the distribution of carriers with respect to time (one
dimension), location (three dimensions), and momentum (three dimensions).
However, numerical solutions for the seven-dimensional carrier distribution
functions are very demanding. The most common solution approach is the stochastic
Monte Carlo method, because the gigabytes of memory requirements of deterministic
direct solution approaches has not been available until recently. As a remedy,
the higher accuracy provided by solutions of the Boltzmann transport equation is
often exchanged for lower computational expense by using simpler models based on
macroscopic quantities such as carrier density and mean carrier velocity. Recent
developments for the deterministic spherical harmonics expansion method have
reduced the computational cost for solving the Boltzmann transport equation,
enabling the computation of carrier distribution functions even for spatially
three-dimensional device simulations within minutes to hours. We summarize recent
progress for the spherical harmonics expansion method and show that small
currents, reasonable execution times, and rare events such as low-frequency
noise, which are all hard or even impossible to simulate with the established
Monte Carlo method, can be handled in a straight-forward manner. The
applicability of the method for important practical applications is demonstrated
for noise simulation, small-signal analysis, hot-carrier degradation, and
avalanche breakdown.
PMID- 27610050
TI - Practices Changes in the Child Protection System to Address the Needs of Parents
With Cognitive Disabilities.
AB - Parents with cognitive disabilities (PCD) are over-represented in the child
protection system. However, the current state of the child protection system is
not well prepared for working with them. Biases that exist against their
parenting, the need for accommodations in assessment and intervention practices,
and specific training in staff and cross systems barriers need to be addressed.
This paper argues for changes that will ensure such parents are more effectively
served and that child protection staff and contract providers are better equipped
to work with them. Specific changes are discussed in assessment and intervention
practices. These changes will require human capacity building and organizational
restructuring. Although empirically based behavioral approaches with PCD will be
emphasized, recent empirical work suggests that social information processing and
neurocognitive problems occur in PCD. Approaches to working with such problems
are emerging and must also be considered and integrated into a blueprint for
change.
PMID- 27610052
TI - The sword of Damocles for the splenectomised: death by OPSI.
AB - The overwhelming post splenectomy infection (OPSI) in splenectomised patients is
a rare but severe infection mostly caused by encapsulated bacteria. We analyse
the case of a 65-year-old female patient who was presented with clinical and
laboratory findings indicating gastroenteritis. Two years years before admission,
the patient underwent a splenectomy for a two stage splenic rupture following
resuscitation for pulmonary embolism. Immunisation of the patient was complete
and timely. As a result of the unspecific clinical presentation, there was a
delay in administration of antibiotics. However, administration of antibiotics
induced a fulminant shock. The patient died 4 hours after attending the hospital
due to a pneumococcal sepsis. The discussion highlights epidemiological and
pathophysiological aspects and potential prevention strategies in the
international context. Vaccination failed in our patient as the isolated
pneumococcal strain (serogroup: 12F) is usually covered by the 23-valent
pneumococcal polysaccharide vaccination (Pneumovax((r))). The case reported here
indicates that there may be a potential benefit of prophylactic antibiotic
treatment within the first 3 years after splenectomy for patients above the age
of 65 years. Awareness of OPSI (prevention strategies, symptoms and treatment)
among patients and their treating physicians is crucial for the improvement of
prognosis. We partly address these issues in a standard operating procedure for
the assessment of splenectomised patients in our departments of emergency
medicine.
PMID- 27610053
TI - Active ageing within the nursing home: a study in Flanders, Belgium.
AB - Nursing homes should support residents' quality of life (QoL). It remains vague,
however, how these facilities can create a QoL enhancing environment. Active
ageing (AA) is a useful framework in this context, since it provides a
multidimensional set of determinants that enhance QoL. This study examined the
current status of AA in nursing homes in Flanders, Belgium. A sample of 383
randomly recruited residents was surveyed on the subjective importance and
experienced reality of the AA determinants as well as on QoL. Based on
descriptive analyses, residents appeared to have a positive QoL and a moderately
positive appraisal of the extent to which nursing homes provide a
multidimensional environment to enhance their QoL. Multivariate analyses showed
that residents' nursing home active ageing (NHAA) experience was positively
related to their QoL and explained 20 % of its variance. Specifically,
psychological factors and participation related positively to QoL. Demographic
variables showed no relationships with QoL, while educational level related
negatively to the NHAA experience. Currently, in Flanders, nursing homes are on
their way to working according to the AA vision, but further efforts are still
needed.
PMID- 27610054
TI - Intergenerational support among migrant families in Europe.
AB - Intergenerational support is important throughout the individual life course and
a major mechanism of cultural continuity. In this study, we analyse support
between older parents and their adult children among international migrant and
non-migrant populations in North, Centre and Southern Europe. Data from the
Survey of Health, Ageing and Retirement in Europe are used to compare upward and
downward practical support, grandparenting, and frequency of contact among 62,213
parent-child dyads. Findings indicate limited differences in support between
migrants and non-migrants as well as between migrants of various origins.
However, persistent differences in intergenerational support across Europe along
a north-south gradient are found irrespective of migrant status.
PMID- 27610055
TI - Providing informal care in a changing society.
AB - The ageing of society is leading to significant reforms in long-term care policy
and systems in many European countries. The cutbacks in professional care are
increasing demand for informal care considerably, from both kin and non-kin. At
the same time, demographic and societal developments such as changing family
structures and later retirement may limit the supply of informal care. This
raises the question as to whether the volume of informal care (in people) will
increase in the years ahead. This paper aims to provide a theoretical answer to
this question in two steps. First, based on different care models and empirical
literature, we develop a behavioural model on individual caregiving, the Informal
Care Model. The model states that, in response to the care recipient's need for
care, the intention to provide care is based on general attitudes, quality of the
relationship, normative beliefs, and perceived barriers. Whether one actually
provides care also depends on the care potential of the social context, being the
family, the social network, and the community. Second, we discuss how current
policy and societal developments may negatively or positively impact on these
mechanisms underlying the provision of informal care. Given the increased need
for care among home-dwelling individuals, the model suggests that more people
will take up the caregiver role in the years ahead contributing to larger and
more diverse care networks. It is concluded that long-term informal care
provision is a complex phenomenon including multiple actors in various contexts.
More research is needed to test the Informal Care Model empirically, preferably
using information on care recipients, informal caregivers and community care in a
dynamic design and in different countries. Such information will increase insight
in the developments in informal care provision in retrenching welfare states.
PMID- 27610057
TI - Effect of Exposure to Portland Cement Dust on the Periodontal Status and on the
Outcome of Non-Surgical Periodontal Therapy.
AB - BACKGROUND: Cement dust contains heavy metals like nickel, cobalt, lead and
chromium, pollutants hazardous to the biotic environment, with adverse impact for
vegetation, human and animal health and ecosystems. OBJECTIVE: To investigate if
long term exposure to cement dust can affect the periodontal health and affect
the outcome of non-surgical periodontal therapy. METHODS: A total of sixty
subjects were included in this study. Forty patients with chronic periodontitis
were grouped into; Group I comprised of 20 patients with chronic periodontitis
working in the Portland Cement Company and Group II comprised of 20 patients with
chronic periodontitis who does not work in cement factories nor live near any of
them. Twenty healthy subjects were included in this study as healthy control
group (Group III). Clinical parameters including gingival index (GI), plaque
index (PI), pocket depth (PD) and clinical attachment loss (CLA) were scored for
all patients before and after periodontal therapy. All patients received non
surgical periodontal therapy together with strict oral hygiene program for one
month. Gingival crevicular fluid (GCF) samples were collected from both groups at
baseline and one month after periodontal therapy. Real time PCR (RT-PCR) was used
to analyze the GCF samples for detection and assessment of the levels of IL-1beta
and TNFalpha. RESULTS: The two studied groups responded well to non-surgical
periodontal treatment and there was no significant difference between GI and GII
(P>0.05). The levels of TNFalpha was higher in GI than in GII before and after
periodontal therapy (P<0.05). The levels of IL-1beta did not show any significant
difference between the two groups at base line (P>0.05), but represented with a
highly significant difference between G1 and GII after periodontal therapy
(P<0.001). A significant positive correlation was found between the levels of
both IL-1beta and TNFalpha and all the clinical parameters in GI before and after
periodontal therapy and in GII before periodontal therapy (P<0.05). CONCLUSION:
It seems that long term exposure to cement dust does not affect the clinical
outcome of non-surgical periodontal treatment but it affects the levels of the
pro-inflammatory mediators leading to more periodontal tissue destruction.
PMID- 27610056
TI - Human papilloma virus genotypes in women from Nayarit, Mexico, with squamous
intraepithelial lesions and cervical cancer.
AB - OBJECTIVE: In Mexico cervical cancer (CC) is the most common cause of death from
neoplasia in women. Study aimed to analyze the current distribution of Human
papillomavirus (HPV) types in women from Nayarit, Mexico, with Squamous
intraepithelial lesions (SIL) and Cervical cancer (CC). METHODOLOGY: Between
January 2011 and July 2013, cervical samples were collected from female residents
of the Mexican state of Nayarit and were analyzed by means of a LINEAR ARRAY(r)
HPV genotyping test. Data analyses were performed using Stata ver. 8.0
statistical software. RESULTS: Of the samples analyzed, 91.2%, HPV DNA was
detected. Of these positive samples, 82% were High-risk (HR) viral types. The
most prevalent HPV genotypes identified were 16, 58, 31, 18, and 70. Forty two
percent of participants had a single infection, while 23 and 26% of participants
were infected with two or more HPV genotypes, respectively. HPV 16 was the most
prevalent genotype identified and was frequently present as a co-infection with
HPV types 18, 51, 52, 59, 66, or 70. CONCLUSION: Women <20 years of age were most
often infected with HPV, and the HPV Quadrivalent vaccine (types 16, 18, 6, and
11), currently available in Mexico, no confers protection against a subset of the
HPV genotypes identified in the present study (58, 31, 70, and 35). Thus, it is
important evaluate the geographical distribution of specific HPV genotypes in all
health of center across Mexico in order to implement a successful vaccination
program and to diagnose CC in its early stages.
PMID- 27610058
TI - Dietary Habits of Saudi Medical Students at University of Dammam.
AB - OBJECTIVE: To evaluate the dietary habits and life style of medical students.
DESIGN METHODS: This is a cross sectional study as self-reported questionnaire
for the male and female medical students at College of Medicine University of
Dammam, eastern province, Kingdom of Saudi Arabia, comparing their habits and
life style according to their gender and to their academic levels; 1(st), 3(rd)
and 6(th) year. RESULTS: 562 students participated in the study with response
rate of 91%, average age: 20.2776+/- 2.06175), males students were 333 (59.25%)
and female students were 229 (40.75%) corresponding to the actual male to female
ratio in this medical school. The majority of the students (91.3%) were consuming
fast foods, majority are males (85%) do it 3 times or more per week, only 8.7%
denied eating fast food with no significant difference between the three academic
levels. Majority of students are aware of the benefits of the vegetables and
fruits and the disadvantage of the soft drinks yet most of them consume a lot of
soft drinks and less of vegetables and fruits. Physical exercise was not done
regularly in 65% of the male medical students and 80% of the female with almost
similar percentage in all the three levels. CONCLUSION: Contrary to the
expectations and regardless of studying in medical college, our medical students;
both male and females at different academic levels are having major bad dietary
habits and life style that is comparable to the general population in the
kingdom.
PMID- 27610059
TI - Sex differences in obesity, dietary habits, and physical activity among urban
middle-class Bangladeshis.
AB - BACKGROUND: The sustained economic growth in Bangladesh during the previous
decade has created a substantial middle-class population, who have adequate
income to spend on food, clothing, and lifestyle management. Along with the
improvements in living standards, has also come negative impact on health for the
middle class. The study objective was to assess sex differences in obesity
prevalence, diet, and physical activity among urban middle-class Bangladeshi.
METHODS: In this cross-sectional study, conducted in 2012, we randomly selected
402 adults from Mohammedpur, Dhaka. The sampling technique was multi-stage random
sampling. We used standardized questionnaires for data collection and measured
height, weight, and waist circumference. RESULTS: Mean age (standard deviation)
was 49.4 (12.7) years. The prevalence of both generalized (79% vs. 53%) and
central obesity (85% vs. 42%) were significantly higher in women than men. Women
reported spending more time watching TV and spending less time walking than men
(p<.05); however, men reported a higher intake of unhealthy foods such as fast
food and soft drinks. CONCLUSIONS: We conclude that the prevalence of obesity is
significantly higher in urban middle-class Bangladeshis than previous urban
estimates, and the burden of obesity disproportionately affects women. Future
research and public health efforts are needed to address this severe obesity
problem and to promote active lifestyles.
PMID- 27610061
TI - Prevalence and trends of overweight and obesity amongst Saudi school children, a
study done by using three noninvasive methods.
AB - Obesity has become a global epidemic. It's level in the Middle Eastern and Asian
countries have reached to an alarming level. Rapid transition of life style and
urbanization has not only affected adults but also the younger population.
OBJECTIVE: This study records the trends of prevalence of obesity and over weight
in the school children of both genders of Al Qassim region by employing three
different non-invasive methods and recorded their differences. SUBJECTS AND
METHODS: This cross-sectional study was conducted on Saudi students of secondary
and intermediate levels between 12-14 years of age. The total number of the
students who participated in the study was 242, 129 males and 113 females. A self
administered pre-coded questionnaire was used. Body mass index, skin fold
thickness and bioelectrical impedance analyzer (BIA) readings were recorded. Data
was analyzed on SPSS version 11. Descriptive statistical analysis was performed.
Chi square test with a P value <0.05, was used to compare the prevalence rates.
RESULTS: Prevalence of obesity and over-weight recorded were higher in the boys
but the rates recorded by three methods have shown a wide variation. Several
factors, such as change in dietary habits, socioeconomic status and the family
history of obesity have shown association but physical inactivity and father's
obesity were found significant contributory factors. There is an urgent need for
intervention to prevent and control obesity and its consequences amongst children
in Saudi Arabia.
PMID- 27610060
TI - The Effects of Below Knee Compression Garments on Functional Performance in
Individuals with Parkinson Disease.
AB - BACKGROUND: Symptoms of Parkinson's disease (PD) include bradykinesia, gait
abnormalities, balance deficits, restless leg syndrome, and muscular fatigue.
Compression garments (CG) have been shown to improve performance in athletes by
increasing venous return and reduce lactic acid. OBJECTIVE: Assess the effect of
compression garments on the performance of 3 standardized functional tests in
persons with PD. METHODOLOGY: The functional tests selected represented strength,
endurance, and mobility measures in individuals with PD. Nineteen males and 2
females (age 48-85) with PD participated in this cross-over design study.
Subjects were randomly assigned to test under two conditions on two separate
days: 1) wearing below knee CG 2) wearing sham stockings. Outcome measures
included 5 Times Sit to Stand (5XSTS), gait speed, and 6 Minute Walk Test (6MWT).
There were seven days between trials. RESULTS: A paired t-test was used for each
dependent variable. Significance was set at p < 0.05. There were no significant
differences found between the CG and sham socks for all outcome measures. Paired
t-tests for the dependent variables were Gait Speed p=.729; 5XSTS p=.880; 6MWT
.265; RPE p. =1.00. CONCLUSION: Data to support the use of compression garments
for enhanced proprioception, muscle power, speed, and endurance is in need of
further study with the PD population. In particular, it is recommended that
future studies assess the possible physiological benefits of compression garments
when worn during exercise interventions.
PMID- 27610062
TI - Effect of Lower Extremity Stretching Exercises on Balance in Geriatric
Population.
AB - BACKGROUND AND OBJECTIVE: The purpose of this study was to find "Effect of lower
extremity stretching exercises on balance in the geriatric population. METHOD: 60
subjects (30 male and 30 female) participated in the study. The subjects
underwent 10 weeks of lower limb stretching exercise program. Pre and post 10
weeks stretching exercise program, the subjects were assessed for balance, using
single limb stance time in seconds and berg balance score. These outcome measures
were analyzed. RESULTS: Pre and post lower extremity stretching on balance was
analyzed using paired t test. Of 60 subjects 50 subjects completed the stretching
exercise program. Paired sample t test analysis showed a significant improvement
in single limb stance time (eyes open and eyes closed) (p<0.001) and berg balance
score (p<0.001). CONCLUSION: Lower extremity stretching exercises enhances
balance in the geriatric population and thereby reduction in the number of falls.
PMID- 27610063
TI - Prevalence and risk factors of gastroparesis-related symptoms among patients with
type 2 diabetes.
AB - BACKGROUND: The prevalence of gastroparesis in type 2 diabetes mellitus (T2DM)
vary widely. Our aim is to estimate the prevalence of clinical symptoms of
gastroparesis among patients with type 2 diabetes mellitus and explore the
relationship between gastroparesis and other risk factors. METHODS: A cross
sectional study evaluating 147 type 2 diabetics using the Gastroparesis Cardinal
Symptoms Index (GCSI). A GCSI Total Score >= 1.90 were chosen as having definite
symptoms of gastroparesis. All patients completed a demographic questionnaire and
interviewed to complete the. Demographic Data, disease duration, Medication,
comorbidities, recent blood glucose and HbA1C were collected and investigated.
RESULTS: The prevalence of clinical symptoms of gastroparesis among type 2
diabetics was 10.8%. Clinical symptoms of gastroparesis were significantly
correlated to HbA1c (p=0.001), blood glucose (p= 0.003), duration of diabetes (p=
0.02) and comorbidities (p=0.009). The most common symptoms were bloating,
stomach fullness and early satiety (63.94%, 55.1% and 48.3% respectively). In
logistic regression analysis, female gender emerged as significant independent
predictors of the presence of at least one symptom. CONCLUSIONS: The prevalence
of clinical symptoms of gastroparesis observed in the Saudi
patientsdiagnosedwithtype2 diabetes was 10.8% and is independently associated
with poor controlled diabetes, hyperglycemia, and long duration of diabetes and
history of Co-morbid conditions.
PMID- 27610065
TI - Knowledge and Attitudes about Basic Life Support among Secondary School Teachers
in Al-Qassim, Saudi Arabia.
AB - OBJECTIVE: Despite the strong evidence that basic life support including
cardiopulmonary resuscitation (CPR) improves survival rates after cardiac events,
the awareness and training among citizens of Saudi Arabia is low. The study
objective was to determine the current level of knowledge and CPR-skills among
secondary school teachers. The second objective was to assess their attitudes and
willingness to participate in regular CPR training. METHOD: A cross-sectional
study was conducted in the secondary schools in Al-Qassim region in 2015. Thirty
of 99 schools were randomly selected; ten teachers from each school were
enrolled. Teachers completed the questionnaire. T-tests were used to examine
whether participants with either previous CPR training or previous resuscitation
experiences had higher scores on the skills test than those without training or
experience. RESULTS: The study included 305 teachers (80% Saudi nationality);
75.4% were males and 66.5% were between the ages of 31 and 50. Among the
teachers, 35.7% had completed CPR training previously; but overall, CPR knowledge
and skills were low (mean =4.0, sd = 1.62). In fact, the average scores did not
differ between those who had training and those who did not. The majority of
teachers wanted more training (64.9%) and were willing to take a free course
(78.4%). CONCLUSION: In Al-Qassim, secondary school teachers lack CPR training
and hence have little knowledge or skills. Teachers are willing and desire to
have more CPR training available to them. Should health officials provide future
training, teachers could serve the community better.
PMID- 27610064
TI - Evidence-Based Practice Beliefs and Implementation among the Nursing Bridge
Program Students of a Saudi University.
AB - OBJECTIVES: This study aimed to measure the evidence-based practice (EBP) beliefs
and implementation among Saudi nursing students enrolled in the bridge program.
It also sought to identify the factors that influence EBP beliefs and
implementation. METHODS: A convenience sample of 188 nursing bridge program
students at a university in Saudi Arabia was surveyed in this descriptive, cross
sectional study. The EBP Beliefs Scale (EBP-B) and the EBP Implementation Scale
(EBPI) were employed to collect data regarding the respondents' beliefs and
implementation of EBP, respectively. Descriptive and inferential statistics were
used to analyze the data. RESULTS: All of the items in the EBP beliefs scale
received good endorsement rate (60.6 - 89.4%). A very low overall mean score of
22.57 was reported by the respondents in the implementation of EBP. The EBP
beliefs of the respondents was primarily influenced by awareness on EBP (beta =
0.26, p <0.001), followed by gender (beta = -0.20, p<0.001), age (beta = 0.17,
p<0.05), and attendance at EBP trainings/seminars (beta = 0.16, p<0.05).
Attendance to EBP training and seminars (beta = 0.19, p<0.01), gender (beta =
0.18, p<0.05) and awareness on EBP (beta = 0.15, p<0.05) were identified as
factors that influence EBP implementation. CONCLUSIONS: Despite the positive
responses on the belief scale, the implementation of EBP by the respondents is
very poor. Education and training courses should be initiated to increase the
implementation of EBP among the nursing bridge program students.
PMID- 27610066
TI - Nicotine Replacement Therapy: An Overview.
AB - Today tobacco use is the single greatest preventable cause of death in the world.
Tobacco use is often incorrectly perceived to be solely a personal choice. This
is contradicted by the fact that when fully aware of the health impact, most
tobacco users want to quit but find it difficult to stop due to the addictiveness
of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence
which temporarily replaces much of the nicotine from tobacco to reduce motivation
to consume tobacco and nicotine withdrawal symptoms, thus easing the transition
from cigarette smoking to complete abstinence. Various alternative nicotine
sources (gum, transdermal patch, nasal spray, inhaler and sublingual
tablets/lozenges) have been incorporated into tobacco cessation programs. Recent
research is more focusing on rapid delivery of nicotine (Nicotine preloading,
true pulmonary inhaler) and immunological approaches (nicotine vaccine) to tackle
nicotine dependence. These NRTs are in general well tolerated and have minimal
adverse effects. The review aims to summarize literature on various modes of
nicotine replacement therapy methods currently used to treat nicotine dependence,
and to give an overview about future possible approaches to treat tobacco use
disorder.
PMID- 27610067
TI - Calcific Metamorphosis: A Review.
AB - Dental trauma to the permanent dentition can lead to clinical complications and
its management may considerably challenge a practitioner. The incidence of pulp
canal obliteration following dental trauma has been reported to be approximately
4 - 24%. Attempting to locate canals following calcific metamorphosis and
negotiating it to full working length may lead to iatrogenic errors such as
fractured instrument and perforation. This review article describes the possible
etiology of Calcific Metamorphosis, its clinical and radiographic features as
well as its management.
PMID- 27610069
TI - Nephrotic syndrome is a rare manifestation of IGA nephropathy.
AB - Nephrotic syndrome is a rare presentation of IgA nephropathy. The degree of
proteinuria in IgA nephropathy predicts poor prognosis. We herein report a
teenager with IGA nephropathy, the nephrotic syndrome and segmental glomerular
scars who after developing complications from high dose corticosteroid therapy
was successfully treated with tacrolimus and low dose prednisone.
PMID- 27610070
TI - Zika - Global Concern.
PMID- 27610068
TI - Vitamin D and extra-skeletal health: causality or consequence.
AB - Vitamin D deficiency /insufficiency is widely recognized as a global health
problem that is likely to be involved in pathogenesis or progression of many
acute and chronic health disorders. Its relation to skeletal health has been
clearly demonstrated and thoroughly examined. This review aims to highlight the
continuous debate about the relation between vitamin D and extra-skeletal health
and whether it is a causality or just an association. Overall, the available
evidence does not meet the criteria for establishing cause-and-effect
relationships because of the limitations of observational studies to corroborate
the causality due to many potential confounders. Moreover, the causal
relationship couldn't be established in randomized studies or in many meta
analyses. This may reflect the fact that vitamin D level reduction is just a
biomarker of ill health. The inflammatory processes involved in the disease
occurrence and the functional limitations of the diseases would have a role in
reducing serum 25-hydroxy vitamin D "25 (OH) D" level, which would explain why
low vitamin D is reported in a wide range of disorders. This may underscore the
possibility of harm instead of benefit of vitamin D supplementation when its
exact role is not fully established, thus many guidelines and interest groups are
still hesitant toward recommending replacement in extra-skeletal disease. Future
directions entails the need for a large well-designed randomized control trials
(RCTs) to resolve the active debate on the benefits of vitamin D replacement for
extra-skeletal disease, and not only that, future studies should establish
specific, clinically relevant effects of vitamin D repletion, provide cut-values
for optimal serum levels of 25 (OH) D, and appropriate doses for non-skeletal
health benefits.
PMID- 27610071
TI - Sensori-Motor Learning with Movement Sonification: Perspectives from Recent
Interdisciplinary Studies.
AB - This article reports on an interdisciplinary research project on movement
sonification for sensori-motor learning. First, we describe different research
fields which have contributed to movement sonification, from music technology
including gesture-controlled sound synthesis, sonic interaction design, to
research on sensori-motor learning with auditory-feedback. In particular, we
propose to distinguish between sound-oriented tasks and movement-oriented tasks
in experiments involving interactive sound feedback. We describe several research
questions and recently published results on movement control, learning and
perception. In particular, we studied the effect of the auditory feedback on
movements considering several cases: from experiments on pointing and visuo-motor
tracking to more complex tasks where interactive sound feedback can guide
movements, or cases of sensory substitution where the auditory feedback can
inform on object shapes. We also developed specific methodologies and
technologies for designing the sonic feedback and movement sonification. We
conclude with a discussion on key future research challenges in sensori-motor
learning with movement sonification. We also point out toward promising
applications such as rehabilitation, sport training or product design.
PMID- 27610072
TI - Supervised, Multivariate, Whole-Brain Reduction Did Not Help to Achieve High
Classification Performance in Schizophrenia Research.
AB - We examined how penalized linear discriminant analysis with resampling, which is
a supervised, multivariate, whole-brain reduction technique, can help
schizophrenia diagnostics and research. In an experiment with magnetic resonance
brain images of 52 first-episode schizophrenia patients and 52 healthy controls,
this method allowed us to select brain areas relevant to schizophrenia, such as
the left prefrontal cortex, the anterior cingulum, the right anterior insula, the
thalamus, and the hippocampus. Nevertheless, the classification performance based
on such reduced data was not significantly better than the classification of data
reduced by mass univariate selection using a t-test or unsupervised multivariate
reduction using principal component analysis. Moreover, we found no important
influence of the type of imaging features, namely local deformations or gray
matter volumes, and the classification method, specifically linear discriminant
analysis or linear support vector machines, on the classification results.
However, we ascertained significant effect of a cross-validation setting on
classification performance as classification results were overestimated even
though the resampling was performed during the selection of brain imaging
features. Therefore, it is critically important to perform cross-validation in
all steps of the analysis (not only during classification) in case there is no
external validation set to avoid optimistically biasing the results of
classification studies.
PMID- 27610074
TI - Comparative Gene Expression Analysis of Two Mouse Models of Autism: Transcriptome
Profiling of the BTBR and En2 (-/-) Hippocampus.
AB - Autism spectrum disorders (ASD) are characterized by a high degree of genetic
heterogeneity. Genomic studies identified common pathological processes
underlying the heterogeneous clinical manifestations of ASD, and transcriptome
analyses revealed that gene networks involved in synapse development, neuronal
activity, and immune function are deregulated in ASD. Mouse models provide unique
tools to investigate the neurobiological basis of ASD; however, a comprehensive
approach to identify transcriptional abnormalities in different ASD models has
never been performed. Here we used two well-recognized ASD mouse models, BTBR
T(+) Itpr3 (tf) /J (BTBR) and Engrailed-2 knockout (En2 (-/-)), to identify
conserved ASD-related molecular signatures. En2 (-/-) mice bear a mutation within
the EN2 transcription factor homeobox, while BTBR is an inbred strain with
unknown genetic defects. Hippocampal RNA samples from BTBR, En2 (-/-) and
respective control (C57Bl/6J and En2 (+/+)) adult mice were assessed for
differential gene expression using microarrays. A total of 153 genes were
similarly deregulated in the BTBR and En2 (-/-) hippocampus. Mouse phenotype and
gene ontology enrichment analyses were performed on BTBR and En2 (-/-)
hippocampal differentially expressed genes (DEGs). Pathways represented in both
BTBR and En2 (-/-) hippocampal DEGs included abnormal behavioral response and
chemokine/MAP kinase signaling. Genes involved in abnormal function of the immune
system and abnormal synaptic transmission/seizures were significantly represented
among BTBR and En2 (-/-) DEGs, respectively. Interestingly, both BTBR and En2 (-/
) hippocampal DEGs showed a significant enrichment of ASD and schizophrenia (SCZ)
associated genes. Specific gene sets were enriched in the two models: microglial
genes were significantly enriched among BTBR DEGs, whereas
GABAergic/glutamatergic postsynaptic genes, FMRP-interacting genes and epilepsy
related genes were significantly enriched among En2 (-/-) DEGs. Weighted
correlation network analysis (WGCNA) performed on BTBR and En2 (-/-) hippocampal
transcriptomes together identified six modules significantly enriched in ASD
related genes. Each of these modules showed a specific enrichment profile in
neuronal and glial genes, as well as in genes associated to ASD comorbidities
such as epilepsy and SCZ. Our data reveal significant transcriptional
similarities and differences between the BTBR and En2 (-/-) hippocampus,
indicating that transcriptome analysis of ASD mouse models may contribute to
identify novel molecular targets for pharmacological studies.
PMID- 27610075
TI - Corrigendum: A Simplified In vitro Experimental Model Encompasses the Essential
Features of Sleep.
AB - [This corrects the article on p. 315 in vol. 10, PMID: 27458335.].
PMID- 27610073
TI - Aberrant Development of Speech Processing in Young Children with Autism: New
Insights from Neuroimaging Biomarkers.
AB - From the time of birth, a newborn is continuously exposed and naturally attracted
to human voices, and as he grows, he becomes increasingly responsive to these
speech stimuli, which are strong drivers for his language development and
knowledge acquisition about the world. In contrast, young children with autism
spectrum disorder (ASD) are often insensitive to human voices, failing to orient
and respond to them. Failure to attend to speech in turn results in altered
development of language and social-communication skills. Here, we review the
critical role of orienting to speech in ASD, as well as the neural substrates of
human voice processing. Recent functional neuroimaging and electroencephalography
studies demonstrate that aberrant voice processing could be a promising marker to
identify ASD very early on. With the advent of refined brain imaging methods,
coupled with the possibility of screening infants and toddlers, predictive brain
function biomarkers are actively being examined and are starting to emerge. Their
timely identification might not only help to differentiate between phenotypes,
but also guide the clinicians in setting up appropriate therapies, and better
predicting or quantifying long-term outcome.
PMID- 27610079
TI - Action Experience and Action Discovery in Medicated Individuals with Parkinson's
Disease.
AB - Parkinson's disease (PD) is a neurodegenerative disorder that markedly affects
voluntary action. While regular dopamine treatment can help restore motor
function, dopamine also influences cognitive portions of the action system.
Previous studies have demonstrated that dopamine medication boosts action-effect
associations, which are crucial for the discovery of new voluntary actions. In
the present study, we investigated whether neural processes involved in the
discovery of new actions are altered in PD participants on regular dopamine
treatment, compared to healthy age-matched controls. We recorded brain
electroencephalography (EEG) activity while PD patients and age-matched controls
performed action discovery (AD) and action control tasks. We found that the
novelty P3, a component normally present when there is uncertainty about the
occurrence of the sensory effect, was enhanced in PD patients. However, AD was
maintained in PD patients, and the novelty P3 demonstrated normal learning
related reductions. Crucially, we found that in PD patients the causal
association between an action and its resulting sensory outcome did not modulate
the amplitude of the feedback correct-related positivity (fCRP), an EEG component
sensitive to the association between an action and its resulting effect.
Collectively, these preliminary results suggest that the formation of long-term
action-outcome representations may be maintained in PD patients on regular
dopamine treatment, but the initial experience of action-effect association may
be affected.
PMID- 27610081
TI - Editorial: Molecular Nanomachines of the Presynaptic Terminal.
PMID- 27610076
TI - Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis.
AB - Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998.
Since their discovery, they have been one of the most studied neuropeptide
systems because of their projecting fields innervating various brain areas. The
orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a
consequence of their system hypofunction. Orexinergic system is also involved in
many other autonomic functions such as feeding, thermoregulation, cardiovascular
and neuroendocrine regulation. The main aim of this mini review article is to
investigate the relationship between ORX and thyroid system regulation. Although
knowledge about the ORX system is evolving, its putative effects on hypothalamic
pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about
ORX control of HPT axis to know better the relationship between them. The studies
that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but
the nature (excitatory or inhibitory) of this possible interaction remains
actually unclear and needs to be confirmed.
PMID- 27610077
TI - Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects
Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical
Circuits during Adulthood.
AB - Normal maturation of sensory information processing in the cortex requires
patterned synaptic activity during developmentally regulated critical periods.
During early development, spontaneous synaptic activity establishes required
patterns of synaptic input, and during later development it influences patterns
of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a
critical position in regulating the flow of patterned sensory information from
the periphery to the cortex. Abnormal thalamocortical inputs may permanently
affect the organization and function of cortical neuronal circuits, especially if
they occur during a critical developmental window. We examined the effect of
cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats
on spontaneous and evoked firing of somatosensory thalamocortical neurons and on
large-scale correlations in the motor thalamocortical circuit. The mean
spontaneous and sensory-evoked firing rate activity and variability were higher
in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and
variability were correlated in uninjured rats, but not correlated in neurons from
CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm)
neurons persisted into adulthood. Additionally, we found that neurons in the
entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had
higher variability and higher levels of burst firing after injury. Correlated
levels of power in local field potentials (LFPs) between the EPN and the motor
cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic
ischemic injury during development leads to abnormal spontaneous and sensory
stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs
likely permanently and detrimentally affect the organization of cortical
circuitry and processing of sensory information. Hypoxic-ischemic injury also
leads to abnormal single neuron and population level activity in the basal
ganglia that may contribute to motor dysfunction after injury. Combination of
deficits in sensory and motor thalamocortical circuit function may negatively
impact sensorimotor integration in CA survivors. Modulation of abnormal activity
patterns post-injury may represent a novel therapeutic target to improve
neurologic function in survivors.
PMID- 27610080
TI - pypet: A Python Toolkit for Data Management of Parameter Explorations.
AB - pypet (Python parameter exploration toolkit) is a new multi-platform Python
toolkit for managing numerical simulations. Sampling the space of model
parameters is a key aspect of simulations and numerical experiments. pypet is
designed to allow easy and arbitrary sampling of trajectories through a parameter
space beyond simple grid searches. pypet collects and stores both simulation
parameters and results in a single HDF5 file. This collective storage allows fast
and convenient loading of data for further analyses. pypet provides various
additional features such as multiprocessing and parallelization of simulations,
dynamic loading of data, integration of git version control, and supervision of
experiments via the electronic lab notebook Sumatra. pypet supports a rich set of
data formats, including native Python types, Numpy and Scipy data, Pandas
DataFrames, and BRIAN(2) quantities. Besides these formats, users can easily
extend the toolkit to allow customized data types. pypet is a flexible tool
suited for both short Python scripts and large scale projects. pypet's various
features, especially the tight link between parameters and results, promote
reproducible research in computational neuroscience and simulation-based
disciplines.
PMID- 27610078
TI - MAOA Influences the Trajectory of Attentional Development.
AB - Attention is vital to success in all aspects of life (Meck and Benson, 2002;
Erickson et al., 2015), hence it is important to identify biomarkers of later
attentional problems early enough to intervene. Our objective was to determine if
any of 11 genes (APOE, BDNF, HTR4, CHRNA4, COMT, DRD4, IGF2, MAOA, SLC5A7,
SLC6A3, and SNAP25) predicted the trajectory of attentional development within
the same group of children between infancy and childhood. We recruited follow up
participants from children who participated as infants in visual attention
studies and used a similar task at both time points. Using multilevel modeling,
we associated changes in the participant's position in the distribution of scores
in infancy to his/her position in childhood with genetic markers on each of 11
genes. While all 11 genes predicted reaction time (RT) residual scores, only
Monoamine oxidase A (MAOA) had a significant interaction including time point. We
conclude that the MAOA single nucleotide polymorphism (SNP) rs1137070 is useful
in predicting which girls are likely to develop slower RTs on an attention task
between infancy and childhood. This early identification is likely to be helpful
in early intervention.
PMID- 27610082
TI - Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification
in Older Adults: Preliminary Results.
AB - Quick correct identification of facial emotions is highly relevant for successful
social interactions. Research suggests that older, compared to young, adults
experience increased difficulty with face and emotion processing skills. While
functional neuroimaging studies suggest age differences in neural processing of
faces and emotions, evidence about age-associated structural brain changes and
their involvement in face and emotion processing is scarce. Using structural
magnetic resonance imaging (MRI), this study investigated the extent to which
volumes of frontal and temporal brain structures were related to reaction time in
accurate identification of facial emotions in 30 young and 30 older adults.
Volumetric segmentation was performed using FreeSurfer and gray matter volumes
from frontal and temporal regions were extracted. Analysis of covariances
(ANCOVAs) models with response time (RT) as the dependent variable and age group
and regional volume, and their interaction, as independent variables were
conducted, controlling for total intracranial volume (ICV). Results indicated
that, in older adults, larger hippocampal volumes were associated with faster
correct facial emotion identification. These preliminary observations suggest
that greater volume in brain regions associated with face and emotion processing
contributes to improved facial emotion identification performance in aging.
PMID- 27610083
TI - Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating
Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-alpha in
Hypertensive Patients with Prediabetes.
AB - OBJECTIVE: To assess the effect of amlodipine and atorvastatin on intercellular
adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-alpha expression, as
endothelial function and inflammation indicators, respectively, in hypertensive
patients with and without prediabetes. METHODS: Forty-five consecutive patients
with hypertension, diagnosed according to JNC7, were divided into two groups
based on the presence (HD group, n = 23) or absence (H group, n = 22) of
prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose
tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent
12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium
combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated
before and after treatment from overnight fasting blood samples was analyzed by
ELISA. RESULTS: In the HD and H groups after vs. before 12-week
amlodipine/atorvastatin treatment, there were significantly (all P < 0.01) lower
levels of ICAM-1 (3.06 +/- 0.34 vs. 4.07 +/- 0.70 pg/ml; 3.26 +/- 0.32 vs. 3.81
+/- 0.60 pg/ml, respectively) and TNF-alpha (78.71 +/- 9.19 vs. 110.94 +/- 10.71
pg/ml; 80.95 +/- 9.33 vs. 101.79 +/- 11.72 pg/ml, respectively), with more
pronounced reductions in HD vs. H group (ICAM-1Delta: 1.01 +/- 0.80 vs. 0.55 +/-
0.64 pg/ml, respectively, P = 0.037; TNF-alphaDelta: 32.23 +/- 14.33 vs. 20.84 +/
14.89 pg/ml, respectively, P = 0.011), independent of the blood pressure (BP)
and cholesterol level reduction. CONCLUSIONS: Amlodipine/atorvastatin improved
endothelial function and inflammation, as reflected by lower circulating levels
of ICAM-1 and TNF-alpha, more prominently in hypertensives with than without
prediabetes. Starting statin treatment before overt diabetes in hypertensives
might thus improve cardiovascular outcomes.
PMID- 27610084
TI - Current Status of the New Antiepileptic Drugs in Chronic Pain.
AB - Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range
of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar
disorder. Due to this situation more than 20 new third-generation AEDs have been
introduced in the market recently. The future design of new AEDs must also have
potential to help in the non-epileptic disorders. The wide acceptance of second
generation AEDs for the management of various non-epileptic disorders has caused
the emergence of generics in the market. The wide use of approved AEDs outside
epilepsy is based on both economic and scientific reasons. Bipolar disorders,
migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most
attractive indication expansion opportunities for anticonvulsant developers,
providing blockbuster revenues. Strong growth in non-epilepsy conditions will see
Pfizer's Lyrica become the market leading brand by 2018. In this review, we
mainly focus on the current status of new AEDs in the treatment of chronic pain
and migraine prophylaxis. AEDs have a strong analgesic potential and this is
demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium
valproate in migraine prophylaxis. At present, data on the new AEDs for non
epileptic conditions are inconclusive. Not all AEDs are effective in the
management of neuropathic pain and migraine. Only those AEDs whose mechanisms of
action are match with pathophysiology of the disease, have potential to show
efficacy in non-epileptic disorder. For this better understanding of the
pathophysiology of the disease and mechanisms of action of new AEDs are essential
requirement before initiating pre-clinical and clinical trials. Many new AEDs
show good results in the animal model and open-label studies but fail to provide
strong evidence at randomized, placebo-controlled trials. The final decision
regarding the clinical efficacy of the particular AEDs in a specific non
epileptic disorder should be withdrawal from randomized placebo trials rather
than open-label studies; otherwise this may lead to off-label uses of drug. The
purpose of the present review is to relate the various mechanisms of action of
new AEDs to pathophysiological mechanisms and clinical efficacy in neuropathic
pain and migraine.
PMID- 27610085
TI - Gene Expression Profiling Reveals Functional Specialization along the Intestinal
Tract of a Carnivorous Teleostean Fish (Dicentrarchus labrax).
AB - High-quality sequencing reads from the intestine of European sea bass were
assembled, annotated by similarity against protein reference databases and
combined with nucleotide sequences from public and private databases. After
redundancy filtering, 24,906 non-redundant annotated sequences encoding 15,367
different gene descriptions were obtained. These annotated sequences were used to
design a custom, high-density oligo-microarray (8 * 15 K) for the transcriptomic
profiling of anterior (AI), middle (MI), and posterior (PI) intestinal segments.
Similar molecular signatures were found for AI and MI segments, which were
combined in a single group (AI-MI) whereas the PI outstood separately, with more
than 1900 differentially expressed genes with a fold-change cutoff of 2.
Functional analysis revealed that molecular and cellular functions related to
feed digestion and nutrient absorption and transport were over-represented in AI
MI segments. By contrast, the initiation and establishment of immune defense
mechanisms became especially relevant in PI, although the microarray expression
profiling validated by qPCR indicated that these functional changes are gradual
from anterior to posterior intestinal segments. This functional divergence
occurred in association with spatial transcriptional changes in nutrient
transporters and the mucosal chemosensing system via G protein-coupled receptors.
These findings contribute to identify key indicators of gut functions and to
compare different fish feeding strategies and immune defense mechanisms acquired
along the evolution of teleosts.
PMID- 27610088
TI - Ionic and Amino Acid Regulation in Hard Clam (Meretrix lusoria) in Response to
Salinity Challenges.
AB - Most marine mollusks are osmoconformers, in that, their body fluid osmolality
changes in the direction of the change in environmental salinity. Marine mollusks
exhibit a number of osmoregulatory mechanisms to cope with either hypo- or
hyperosmotic stress. The effects of changes in salinity on the osmoregulatory
mechanisms of the hard clam (Meretrix lusoria, an economically important species
of marine bivalve for Taiwan) have not been determined. In this study, we
examined the effect of exposure to hypo (100/00)- and hyper (350/00)-osmotic
salinity on hard clams raised at their natural salinity (200/00). The osmolality,
[Na(+)], and [Cl(-)] of the hard clam hemolymph were changed in the same
direction as the surrounding salinity. Further, the contents of total free amino
acids including taurine in the gills and mantles were significantly upregulated
in hard clam with increasing salinity. The gill Na(+), K(+)-ATPase (NKA)
activity, the important enzyme regulating cellular inorganic ions, was not
affected by the changed salinity. Mantle NKA activity, however, was stimulated in
the 350/00 SW treatment. The taurine transporter (TAUT) is related to the
regulation of intracellular contents of taurine, the dominant osmolyte. Herein, a
TAUT gene of hard clam was cloned and a TAUT antibody was derived for the
immunoblotting. The TAUT mRNA expression of the mantle in hard clam was
significantly stimulated in 350/00 SW, but protein expression was not modulated
by the changed salinity. In gills of the hard clam with 100/00 SW, both TAUT mRNA
and protein expressions were significantly stimulated, and it may reflect a
feedback regulation from the decreased gills taurine content under long-term
hypoosmotic acclimation. These findings suggest that TAUT expression is regulated
differently in gills and mantles following exposure to alterations in
environmental salinity. Taken together, this study used the physiological,
biochemical and molecular approaches to simultaneously explore the osmoregulation
in tissues of hard clam and may further help to understand the osmoregulation in
bivalves.
PMID- 27610087
TI - Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure
Model Induced by Chronic Volume Overload.
AB - Volume overload leads to development of eccentric cardiac hypertrophy and heart
failure. In our previous report, we have shown myocyte hypertrophy with no
fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of
aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological
and protein expression changes in the left ventricle and correlate them with
phenotypic severity based upon ventricles to body weight ratio. ECG analysis
showed increased amplitude and duration of the P wave, prolongation of PR and QRS
interval, ST segment elevation and decreased T wave amplitude in the fistula
group. Optical mapping showed a prolongation of action potential duration in the
hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped
curve, with a significant increase in the mild cases and there was a negative
correlation of both minimal and maximal CV with heart to body weight ratio. Since
the CV is influenced by gap junctional coupling as well as the autonomic nervous
system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl
transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation,
respectively. At the protein level, we confirmed a significant decrease in total
and phosphorylated connexin43 that was proportional to the level of hypertrophy,
and similarly decreased levels of TH and ChAT. Even at a single time-point,
severity of morphological phenotype correlates with progression of molecular and
electrophysiological changes, with the most hypertrophied hearts showing the most
severe changes that might be related to arrhythmogenesis.
PMID- 27610086
TI - Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis,
Breakdown, and Insulin Resistance-A Qualitative Review.
AB - The ever increasing burden of an aging population and pandemic of metabolic
syndrome worldwide demands further understanding of the modifiable risk factors
in reducing disability and morbidity associated with these conditions. Disuse
skeletal muscle atrophy (sometimes referred to as "simple" atrophy) and insulin
resistance are "non-pathological" events resulting from sedentary behavior and
periods of enforced immobilization e.g., due to fractures or elective orthopedic
surgery. Yet, the processes and drivers regulating disuse atrophy and insulin
resistance and the associated molecular events remain unclear-especially in
humans. The aim of this review is to present current knowledge of relationships
between muscle protein turnover, insulin resistance and muscle atrophy during
disuse, principally in humans. Immobilization lowers fasted state muscle protein
synthesis (MPS) and induces fed-state "anabolic resistance." While a lack of
dynamic measurements of muscle protein breakdown (MPB) precludes defining a
definitive role for MPB in disuse atrophy, some proteolytic "marker" studies
(e.g., MPB genes) suggest a potential early elevation. Immobilization also
induces muscle insulin resistance (IR). Moreover, the trajectory of muscle
atrophy appears to be accelerated in persistent IR states (e.g., Type II
diabetes), suggesting IR may contribute to muscle disuse atrophy under these
conditions. Nonetheless, the role of differences in insulin sensitivity across
distinct muscle groups and its effects on rates of atrophy remains unclear.
Multifaceted time-course studies into the collective role of insulin resistance
and muscle protein turnover in the setting of disuse muscle atrophy, in humans,
are needed to facilitate the development of appropriate countermeasures and
efficacious rehabilitation protocols.
PMID- 27610089
TI - Music Regulators in Two String Quartets: A Comparison of Communicative Behaviors
between Low- and High-Stress Performance Conditions.
AB - In ensemble performances, group members use particular bodily behaviors as a sort
of "language" to supplement the lack of verbal communication. This article
focuses on music regulators, which are defined as signs to other group members
for coordinating performance. The following two music regulators are considered:
body gestures for articulating attacks (a set of movements externally directed
that are used to signal entrances in performance) and eye contact. These
regulators are recurring observable behaviors that play an important role in non
verbal communication among ensemble members. To understand how they are used by
chamber musicians, video recordings of two string quartet performances (Quartet A
performing Bartok and Quartet B performing Haydn) were analyzed under two
conditions: a low stress performance (LSP), undertaken in a rehearsal setting,
and a high stress performance (HSP) during a public recital. The results provide
evidence for more emphasis in gestures for articulating attacks (i.e., the
perceived strength of a performed attack-type body gesture) during HSP than LSP.
Conversely, no significant differences were found for the frequency of eye
contact between HSP and LSP. Moreover, there was variability in eye contact
during HSP and LSP, showing that these behaviors are less standardized and may
change according to idiosyncratic performance conditions. Educational
implications are discussed for improving interpersonal communication skills
during ensemble performance.
PMID- 27610090
TI - Locality and Word Order in Active Dependency Formation in Bangla.
AB - Research on filler-gap dependencies has revealed that there are constraints on
possible gap sites, and that real-time sentence processing is sensitive to these
constraints. This work has shown that comprehenders have preferences for
potential gap sites, and immediately detect when these preferences are not met.
However, neither the mechanisms that select preferred gap sites nor the
mechanisms used to detect whether these preferences are met are well-understood.
In this paper, we report on three experiments in Bangla, a language in which gaps
may occur in either a pre-verbal embedded clause or a post-verbal embedded
clause. This word order variation allows us to manipulate whether the first gap
linearly available is contained in the same clause as the filler, which allows us
to dissociate structural locality from linear locality. In Experiment 1, an
untimed ambiguity resolution task, we found a global bias to resolve a filler-gap
dependency with the first gap linearly available, regardless of structural
hierarchy. In Experiments 2 and 3, which use the filled-gap paradigm, we found
sensitivity to disruption only when the blocked gap site is both structurally and
linearly local, i.e., the filler and the gap site are contained in the same
clause. This suggests that comprehenders may not show sensitivity to the
disruption of all preferred gap resolutions.
PMID- 27610091
TI - Emotional Creativity as Predictor of Intrinsic Motivation and Academic Engagement
in University Students: The Mediating Role of Positive Emotions.
AB - OBJECTIVE: Emotional creativity (EC) implies experiencing a complex emotional
life, which is becoming increasingly necessary in societies that demand
innovation and constant changes. This research studies the relation of EC as a
dispositional trait with intrinsic motivation (IM) and academic engagement (AE).
METHODS: A sample of 428 university Chilean students, 36.5% men and 63.5% women,
with ages from 18 to 45 years-old (M = 20.37; DT = 2.71). Additionally, the
mediating function of class-related positive emotions in this relation is
explored. RESULTS: The obtained data indicate that developing high levels of
dispositional EC enhances the activation of positive emotions, such as gratitude,
love and hope, in the classroom. Furthermore, EC predicts IM and AE of university
students by the experience of positive emotions. CONCLUSION: These results compel
us to be aware of the importance that university students can understand the
complexity of the emotional processes they undergo. A greater control of these
emotions would allow students to maintain higher levels of interest in their
studies at the different educational stages and to avoid the risk of school
failure.
PMID- 27610092
TI - Attachment Security Balances Perspectives: Effects of Security Priming on Highly
Optimistic and Pessimistic Explanatory Styles.
AB - Highly optimistic explanatory style (HOES) and highly pessimistic explanatory
style (HPES) are two maladaptive ways to explain the world and may have roots in
attachment insecurity. The current study aims to explore the effects of security
priming - activating supportive representations of attachment security - on
ameliorating these maladaptive explanatory styles. 57 participants with HOES and
57 participants with HPES were randomized into security priming and control
conditions. Their scores of overall optimistic attribution were measured before
and after priming. Security priming had a moderating effect: the security primed
HOES group exhibited lower optimistic attribution, while the security primed HPES
group evinced higher scores of optimistic attribution. Furthermore, the security
primed HOES group attributed positive outcomes more externally, while the
security primed HPES group attributed successful results more internally. The
results support the application of security priming interventions on maladaptive
explanatory styles. Its potential mechanism and directions for future study are
also discussed.
PMID- 27610093
TI - A Longitudinal Study of the Predictors of Perceived Procedural Justice in
Australian University Staff.
AB - PURPOSE: This study examined the factors that predict employees' perceptions of
procedural justice in university settings. The paper also reviews the ethical
aspects of justice and psychological contracts within employment relationships.
DESIGN/METHODOLOGY/APPROACH: The study examined the predictors of perceived
procedural justice in a two-wave longitudinal sample of 945 employees from 13
universities by applying the Job Demands-Resources theoretical model of stress.
The proposed predictors were classified into two categories: Job demands of work
pressure and work-home conflict; and job resources of job security, autonomy,
trust in senior management, and trust in supervisor. The predictor model also
examined job satisfaction and affective organizational commitment, demographic
(age, gender, tenure, role) and individual characteristics (negative affectivity,
job involvement) as well as Time 1 (T1) perceptions of procedural justice to
ensure that tests were rigorous. FINDINGS: A series of hierarchical multiple
regression analyses found that job satisfaction at T1 was the strongest predictor
of perceived procedural justice at Time 2. Employees' trust in senior management,
and their length of tenure also positively predicted justice perceptions. There
were also differences between academic and non-academic staff groups, as non
academic employees' level of job satisfaction, trust in senior management, and
their length of organizational tenure predicted procedural justice perceptions,
whereas for academics, only job satisfaction predicted perceived justice. For the
"all staff" category, job satisfaction was a dominant and enduring predictor of
justice, and employees' trust in senior management also predicted justice.
RESEARCH LIMITATIONS/IMPLICATIONS: Results highlight the importance of workplace
factors in enhancing fair procedures to encourage reciprocity from employees. As
perceived procedural justice is also conceptually linked to the psychological
contract between employees-employers, it is possible that employees' levels of
job satisfaction and perceptions of trust in senior management, relative to other
work attitudinal outcomes, may be more effective for improving the broader
working environment, and promoting staff morale. ORIGINALITY/VALUE: This study
adds to research on applied business ethics as it focuses on the ethical aspects
of perceived procedural justice and highlights the importance of workplace
factors in enhancing fair procedures in organizational policy to encourage
reciprocity and promote healthy organizational environments.
PMID- 27610094
TI - Editorial: Creativity and Mental Imagery.
PMID- 27610096
TI - The Exercise-Affect-Adherence Pathway: An Evolutionary Perspective.
AB - The low rates of regular exercise and overall physical activity (PA) in the
general population represent a significant public health challenge. Previous
research suggests that, for many people, exercise leads to a negative affective
response and, in turn, reduced likelihood of future exercise. The purpose of this
paper is to examine this exercise-affect-adherence relationship from an
evolutionary perspective. Specifically, we argue that low rates of physical
exercise in the general population are a function of the evolved human tendency
to avoid unnecessary physical exertion. This innate tendency evolved because it
allowed our evolutionary ancestors to conserve energy for physical activities
that had immediate adaptive utility such as pursuing prey, escaping predators,
and engaging in social and reproductive behaviors. The commonly observed negative
affective response to exercise is an evolved proximate psychological mechanism
through which humans avoid unnecessary energy expenditure. The fact that the
human tendencies toward negative affective response to and avoidance of
unnecessary physical activities are innate does not mean that they are
unchangeable. Indeed, it is only because of human-engineered changes in our
environmental conditions (i.e., it is no longer necessary for us to work for our
food) that our predisposition to avoid unnecessary physical exertion has become a
liability. Thus, it is well within our capabilities to reengineer our
environments to once again make PA necessary or, at least, to serve an immediate
functional purpose. We propose a two-pronged approach to PA promotion based on
this evolutionary functional perspective: first, to promote exercise and other
physical activities that are perceived to have an immediate purpose, and second,
to instill greater perceived purpose for a wider range of physical activities. We
posit that these strategies are more likely to result in more positive (or less
negative) affective responses to exercise, better adherence to exercise programs,
and higher rates of overall PA.
PMID- 27610097
TI - Dancing with Disease: A Dancer's Reflections on Moving with People with
Parkinson's and Memory Loss.
PMID- 27610095
TI - Identifying Oneself with the Face of Someone Else Impairs the Egocentered Visuo
spatial Mechanisms: A New Double Mirror Paradigm to Study Self-other Distinction
and Interaction.
AB - Looking at our face in a mirror is one of the strongest phenomenological
experiences of the Self in which we need to identify the face as reflected in the
mirror as belonging to us. Recent behavioral and neuroimaging studies reported
that self-face identification not only relies upon visual-mnemonic representation
of one's own face but also upon continuous updating and integration of visuo
tactile signals. Therefore, bodily self-consciousness plays a major role in self
face identification, with respect to interplay between unisensory and
multisensory processing. However, if previous studies demonstrated that the
integration of multisensory body-related signals contributes to the visual
processing of one's own face, there is so far no data regarding how self-face
identification, inversely, contributes to bodily self-consciousness. In the
present study, we tested whether self-other face identification impacts either
the egocentered or heterocentered visuo-spatial mechanisms that are core
processes of bodily self-consciousness and sustain self-other distinction. For
that, we developed a new paradigm, named "Double Mirror." This paradigm,
consisting of a semi-transparent double mirror and computer-controlled Light
Emitting Diodes, elicits self-other face merging illusory effect in ecologically
more valid conditions, i.e., when participants are physically facing each other
and interacting. Self-face identification was manipulated by exposing pairs of
participants to an Interpersonal Visual Stimulation in which the reflection of
their faces merged in the mirror. Participants simultaneously performed visuo
spatial and mental own-body transformation tasks centered on their own face
(egocentered) or the face of their partner (heterocentered) in the pre- and post
stimulation phase. We show that self-other face identification altered the
egocentered visuo-spatial mechanisms. Heterocentered coding was preserved. Our
data suggest that changes in self-face identification induced a bottom-up
conflict between the current visual representation and the stored mnemonic
representation of one's own face which, in turn, top-down impacted bodily self
consciousness.
PMID- 27610099
TI - The Salivary Microbiome in Polycystic Ovary Syndrome (PCOS) and Its Association
with Disease-Related Parameters: A Pilot Study.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrine
condition of unclear etiology characterized by hyperandrogenism,
oligo/amenorrhoea, and polycystic ovarian morphology. PCOS is often complicated
by infertility, overweight/obesity, insulin resistance, and low-grade
inflammation. The gut microbiome is known to contribute to several of these
conditions. Recently, an association between stool and saliva microbiome
community profiles was shown, making saliva a possible convenient, non-invasive
sample type for detecting gut microbiome changes in systemic disease. In this
study, we describe the saliva microbiome of PCOS patients and the association of
microbiome features with PCOS-related parameters. METHODS: 16S rRNA gene amplicon
sequencing was performed on saliva samples from 24 PCOS patients and 20 healthy
controls. Data processing and microbiome analyses were conducted in mothur and
QIIME. All study subjects were characterized regarding reproductive, metabolic,
and inflammatory parameters. RESULTS: PCOS patients showed a decrease in bacteria
from the phylum Actinobacteria and a borderline significant shift in bacterial
community composition in unweighted UniFrac analysis. No differences between
patients and controls were found in alpha diversity, weighted UniFrac analysis,
or on other taxonomic levels. We found no association of saliva alpha diversity,
beta diversity, or taxonomic composition with serum testosterone,
oligo/amenorrhoea, overweight, insulin resistance, inflammatory markers, age, or
diet. CONCLUSIONS: In this pilot study, patients with PCOS showed a reduced
salivary relative abundance of Actinobacteria. Reproductive and metabolic
components of the syndrome were not associated with saliva microbiome parameters,
indicating that the majority of between-subject variation in saliva microbiome
profiles remains to be explained.
PMID- 27610100
TI - Antifungal Effect of Novel 2-Bromo-2-Chloro-2-(4-Chlorophenylsulfonyl)-1
Phenylethanone against Candida Strains.
AB - We investigated the antifungal activity of novel a 2-bromo-2-chloro-2-(4
chlorophenylsulfonyl)-1-phenylethanone (compound 4). The synthesis of compound 4
was commenced from sodium 4-chlorobenzene sulfinate and the final product was
obtained by treatment of alpha-chloro-beta-keto-sulfone with sodium hypobromite.
The sensitivity of 63 clinical isolates belonging to the most relevant Candida
species toward compound 4 using the method M27-A3 was evaluated. We observed
among most of the clinical strains of C. albicans MIC ranging from 0.00195 to
0.0078 MUg/mL. Compound 4 at 32 MUg/mL exhibited fungicidal activity against nine
Candida strains tested using the MFC assay. Compound 4 displayed anti-Candida
activity (with clear endpoint) against 22% of clinical strains of Candida. Under
compound 4, Candida susceptibility and tolerance, namely paradoxical effect (PG),
was found for only two clinical isolates (C. glabrata and C. parapsilosis) and
reference strain 14053 using both M27-A3 and MFC method. We found that compound 4
does not induce toxicity in vivo against larvae of Galleria mellonella (>=97%
survival) and it displays reduced toxicity on mammalian cells in vitro (< CC20 at
64 MUg/mL). Furthermore, XTT assay denoted clear metabolic activity of sessile
cells in the presence of compound 4. Thus, the effect of compound 4 on formed C.
albicans biofilms was minimal. Moreover, strain 90028 exhibited no defects in
hyphal growth on Caco-2 monolayer under compound 4 influence at MIC = 16 MUg/mL.
The MIC values of compound 4 against C. albicans 90028, in medium with sorbitol
did not suggest that compound 4 acts by inhibiting fungal cell wall synthesis.
Our findings with compound 4 suggest a general strategy for antifungal agent
development that might be useful in limiting the emergence of resistance in
Candida strains.
PMID- 27610101
TI - Superposition of Individual Activities: Urea-Mediated Suppression of Nitrate
Uptake in the Dinoflagellate Prorocentrum minimum Revealed at the Population and
Single-Cell Levels.
AB - Dinoflagellates readily use diverse inorganic and organic compounds as nitrogen
sources, which is advantageous in eutrophied coastal areas exposed to high loads
of anthropogenic nutrients, e.g., urea, one of the most abundant organic nitrogen
substrates in seawater. Cell-to-cell variability in nutritional physiology can
further enhance the diversity of metabolic strategies among dinoflagellates of
the same species, but it has not been studied in free-living microalgae. We
applied stable isotope tracers, isotope ratio mass spectrometry and nanoscale
secondary ion mass spectrometry (NanoSIMS) to investigate the response of
cultured nitrate-acclimated dinoflagellates Prorocentrum minimum to a sudden
input of urea and the effect of urea on the concurrent nitrate uptake at the
population and single-cell levels. We demonstrate that inputs of urea lead to
suppression of nitrate uptake by P. minimum, and urea uptake exceeds the
concurrent uptake of nitrate. Individual dinoflagellate cells within a population
display significant heterogeneity in the rates of nutrient uptake and extent of
the urea-mediated inhibition of the nitrate uptake, thus forming several groups
characterized by different modes of nutrition. We conclude that urea originating
from sporadic sources is rapidly utilized by dinoflagellates and can be used in
biosynthesis or stored intracellularly depending on the nutrient status;
therefore, sudden urea inputs can represent one of the factors triggering or
supporting harmful algal blooms. Significant physiological heterogeneity revealed
at the single-cell level is likely to play a role in alleviation of intra
population competition for resources and can affect the dynamics of phytoplankton
populations and their maintenance in natural environments.
PMID- 27610102
TI - Microbial Diversity and Biochemical Analysis of Suanzhou: A Traditional Chinese
Fermented Cereal Gruel.
AB - Suanzhou as a traditional Chinese gruel is fermented from proso millet and
millet. The biochemical analysis showed Suanzhou had relatively high
concentrations of lactic acid, acetic acid, and free amino acids. The
metagenomics of Suanzhou were studied, with the analysis of the V4 region of 16S
rRNA gene, the genera Lactobacillus and Acetobacter were found dominant with the
average abundance of 58.2 and 24.4%, respectively; and with the analysis of the
ITS1 region between 18S and 5.8S rRNA genes, 97.3% of the fungal community was
found belonging to the genus Pichia and 2.7% belonging to five other genera.
Moreover, the isolates recovered from 59 Suanzhou samples with various media were
identified with the 16S rRNA or 18S rRNA gene analyses. Lactobacillus fermentum
(26.9%), L. pentosus (19.4%), L. casei (17.9%), and L. brevis (16.4%) were the
four dominant Lactobacillus species; Acetobacter lovaniensis (38.1%), A. syzygii
(16.7%), A. okinawensis (16.7%), and A. indonesiensis (11.9%) were the four
dominant Acetobacter species; and Pichia kudriavzevii (55.8%) and Galactomyces
geotrichum (23.1%) were the two dominant fungal species. Additionally, L.
pentosus p28-c and L. casei h28-c1 were selected for the fermentations mimicking
the natural process. Collectively, our data demonstrate that Suanzhou is a
nutritional food high in free amino acids and organic acids. Diverse
Lactobacillus, Acetobacter, and yeast species are identified as the dominant
microorganisms in Suanzhou. The isolated strains can be further characterized and
used as starters for the industrial production of Suanzhou safely.
PMID- 27610098
TI - Interplay between Inflammation and Cellular Stress Triggered by Flaviviridae
Viruses.
AB - The Flaviviridae family comprises several human pathogens, including Dengue,
Zika, Yellow Fever, West Nile, Japanese Encephalitis viruses, and Hepatitis C
Virus. Those are enveloped, single-stranded positive sense RNA viruses, which
replicate mostly in intracellular compartments associated to endoplasmic
reticulum (ER) and Golgi complex. Virus replication results in abundant viral
RNAs and proteins, which are recognized by cellular mechanisms evolved to prevent
virus infection, resulting in inflammation and stress responses. Virus RNA
molecules are sensed by Toll-like receptors (TLRs), RIG-I-like receptors (RIG-I
and MDA5) and RNA-dependent protein kinases (PKR), inducing the production of
inflammatory mediators and interferons. Simultaneously, the synthesis of virus
RNA and proteins are distinguished in different compartments such as
mitochondria, ER and cytoplasmic granules, triggering intracellular stress
pathways, including oxidative stress, unfolded protein response pathway, and
stress granules assembly. Here, we review the new findings that connect the
inflammatory pathways to cellular stress sensors and the strategies of
Flaviviridae members to counteract these cellular mechanisms and escape immune
response.
PMID- 27610103
TI - The Streptococcus pneumoniae pezAT Toxin-Antitoxin System Reduces beta-Lactam
Resistance and Genetic Competence.
AB - Chromosomally encoded Type II Toxin-Antitoxin operons are ubiquitous in bacteria
and archaea. Antitoxins neutralize the toxic effect of cognate Toxins by protein
protein interactions and sequestering the active residues of the Toxin. Toxins
target essential bacterial processes, mostly translation and replication.
However, one class apart is constituted by the PezAT pair because the PezT toxin
target cell wall biosynthesis. Here, we have examined the role of the pezAT toxin
antitoxin genes in its natural host, the pathogenic bacterium Streptococcus
pneumoniae. The pezAT operon on Pneumococcal Pathogenicity Island 1 was deleted
from strain R6 and its phenotypic traits were compared with those of the wild
type. The mutant cells formed shorter chains during exponential phase, leading to
increased colony-forming units. At stationary phase, the mutant was more
resilient to lysis. Importantly, the mutant exhibited higher resistance to
antibiotics targeting cell walls (beta-lactams), but not to antibiotics acting at
other levels. In addition, the mutants also showed enhanced genetic competence.
We suggest that PezAT participates in a subtle equilibrium between loss of
functions (resistance to beta-lactams and genetic competence) and gain of other
traits (virulence).
PMID- 27610104
TI - The Response Regulator YycF Inhibits Expression of the Fatty Acid Biosynthesis
Repressor FabT in Streptococcus pneumoniae.
AB - The YycFG (also known as WalRK, VicRK, MicAB, or TCS02) two-component system
(TCS) is highly conserved among Gram-positive bacteria with a low G+C content. In
Streptococcus pneumoniae the YycF response regulator has been reported to be
essential due to its control of pcsB gene expression. Previously we showed that
overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes
involved in cell wall metabolism and fatty acid biosynthesis, giving rise to
anomalous cell division and increased chain length of membrane fatty acids. Here,
we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a
TIGR4 mutant depleted of YycG, and analyzed their effects on expression of
proteins involved in fatty acid biosynthesis during activation of the TCS. We
demonstrate that transcription of the fab genes and levels of their products were
only altered in the YycF overexpressing strain, indicating that the
unphosphorylated form of YycF is involved in the regulation of fatty acid
biosynthesis. In addition, DNA-binding assays and in vitro transcription
experiments with purified YycF and the promoter region of the FabTH-acp operon
support a direct inhibition of transcription of the FabT repressor by YycF, thus
confirming the role of the unphosphorylated form in transcriptional regulation.
PMID- 27610105
TI - Sequence-Based Screening for Rare Enzymes: New Insights into the World of AMDases
Reveal a Conserved Motif and 58 Novel Enzymes Clustering in Eight Distinct
Families.
AB - Arylmalonate Decarboxylases (AMDases, EC 4.1.1.76) are very rare and mostly
underexplored enzymes. Currently only four known and biochemically characterized
representatives exist. However, their ability to decarboxylate alpha
disubstituted malonic acid derivatives to optically pure products without
cofactors makes them attractive and promising candidates for the use as
biocatalysts in industrial processes. Until now, AMDases could not be separated
from other members of the aspartate/glutamate racemase superfamily based on their
gene sequences. Within this work, a search algorithm was developed that enables a
reliable prediction of AMDase activity for potential candidates. Based on
specific sequence patterns and screening methods 58 novel AMDase candidate genes
could be identified in this work. Thereby, AMDases with the conserved sequence
pattern of Bordetella bronchiseptica's prototype appeared to be limited to the
classes of Alpha-, Beta-, and Gamma-proteobacteria. Amino acid homologies and
comparison of gene surrounding sequences enabled the classification of eight
enzyme clusters. Particularly striking is the accumulation of genes coding for
different transporters of the tripartite tricarboxylate transporters family, TRAP
transporters and ABC transporters as well as genes coding for mandelate
racemases/muconate lactonizing enzymes that might be involved in substrate uptake
or degradation of AMDase products. Further, three novel AMDases were
characterized which showed a high enantiomeric excess (>99%) of the (R)
enantiomer of flurbiprofen. These are the recombinant AmdA and AmdV from
Variovorax sp. strains HH01 and HH02, originated from soil, and AmdP from
Polymorphum gilvum found by a data base search. Altogether our findings give new
insights into the class of AMDases and reveal many previously unknown enzyme
candidates with high potential for bioindustrial processes.
PMID- 27610106
TI - New Genomic Insights into "Entotheonella" Symbionts in Theonella swinhoei:
Mixotrophy, Anaerobic Adaptation, Resilience, and Interaction.
AB - "Entotheonella" (phylum "Tectomicrobia") is a filamentous symbiont that produces
almost all known bioactive compounds derived from the Lithistida sponge Theonella
swinhoei. In contrast to the comprehensive knowledge of its secondary metabolism,
knowledge of its lifestyle, resilience, and interaction with the sponge host and
other symbionts remains rudimentary. In this study, we obtained two
"Entotheonella" genomes from T. swinhoei from the South China Sea through
metagenome binning, and used a RASTtk pipeline to achieve better genome
annotation. The high average nucleotide index values suggested they were the same
phylotypes as the two "Entotheonella" phylotypes from T. swinhoei from the Japan
Sea. Genomic features related to utilization of various carbon sources, peptidase
secretion, CO2 fixation, sulfate reduction, anaerobic respiration, and
denitrification indicated the mixotrophic nature of "Entotheonella." The
endospore-forming potential along with metal- and antibiotic resistance indicated
"Entotheonella" was highly resilient to harsh conditions. The potential for
endospore formation also explained the widespread distribution of "Entotheonella"
to some extent. The discovery of Type II (general secretion pathway proteins and
the Widespread Colonization Island) and Type VI secretion systems in
"Entotheonella" suggested it could secrete extracellular hydrolases, form tight
adhesion, act against phagocytes, and kill other prokaryotes. Overall, the newly
discovered genomic features suggest "Entotheonella" is a highly competitive
member of the symbiotic community of T. swinhoei.
PMID- 27610109
TI - Corrigendum: Characterization of T-bet and Eomes in Peripheral Human Immune
Cells.
AB - [This corrects the article on p. 217 in vol. 5, PMID: 24860576.].
PMID- 27610107
TI - Virulence Factors of Aeromonas hydrophila: In the Wake of Reclassification.
AB - The ubiquitous "jack-of-all-trades," Aeromonas hydrophila, is a freshwater, Gram
negative bacterial pathogen under revision in regard to its phylogenetic and
functional affiliation with other aeromonads. While virulence factors are
expectedly diverse across A. hydrophila strains and closely related species, our
mechanistic knowledge of the vast majority of these factors is based on the
molecular characterization of the strains A. hydrophila AH-3 and SSU, which were
reclassified as A. piscicola AH-3 in 2009 and A. dhakensis SSU in 2013.
Individually, these reclassifications raise important questions involving the
applicability of previous research on A. hydrophila virulence mechanisms;
however, this issue is exacerbated by a lack of genomic data on other research
strains. Collectively, these changes represent a fundamental gap in the
literature on A. hydrophila and confirm the necessity of biochemical, molecular,
and morphological techniques in the classification of research strains that are
used as a foundation for future research. This review revisits what is known
about virulence in A. hydrophila and the feasibility of using comparative
genomics in light of this phylogenetic revision. Conflicting data between
virulence factors, secretion systems, quorum sensing, and their effect on A.
hydrophila pathogenicity appears to be an artifact of inappropriate taxonomic
comparisons and/or be due to the fact that these properties are strain-specific.
This review audits emerging data on dominant virulence factors that are present
in both A. dhakensis and A. hydrophila in order to synthesize existing data with
the aim of locating where future research is needed.
PMID- 27610108
TI - Bacterial Abilities and Adaptation Toward the Rhizosphere Colonization.
AB - The rhizosphere harbors one of the most complex, diverse, and active plant
associated microbial communities. This community can be recruited by the plant
host to either supply it with nutrients or to help in the survival under
stressful conditions. Although selection for the rhizosphere community is
evident, the specific bacterial traits that make them able to colonize this
environment are still poorly understood. Thus, here we used a combination of
community level physiological profile (CLPP) analysis and 16S rRNA gene
quantification and sequencing (coupled with in silico analysis and metagenome
prediction), to get insights on bacterial features and processes involved in
rhizosphere colonization of sugarcane. CLPP revealed a higher metabolic activity
in the rhizosphere compared to bulk soil, and suggested that D-galacturonic acid
plays a role in bacterial selection by the plant roots (supported by results of
metagenome prediction). Quantification of the 16S rRNA gene confirmed the higher
abundance of bacteria in the rhizosphere. Sequence analysis showed that of the
252 classified families sampled, 24 were significantly more abundant in the bulk
soil and 29 were more abundant in the rhizosphere. Furthermore, metagenomes
predicted from the 16S rRNA gene sequences revealed a significant higher
abundance of predicted genes associated with biofilm formation and with
horizontal gene transfer (HGT) processes. In sum, this study identified major
bacterial groups and their potential abilities to occupy the sugarcane
rhizosphere, and indicated that polygalacturonase activity and HGT events may be
important features for rhizosphere colonization.
PMID- 27610110
TI - Fluorescent Pseudomonas Strains with only Few Plant-Beneficial Properties Are
Favored in the Maize Rhizosphere.
AB - Plant Growth-Promoting Rhizobacteria (PGPR) enhance plant health and growth using
a variety of traits. Effective PGPR strains typically exhibit multiple plant
beneficial properties, but whether they are better adapted to the rhizosphere
than PGPR strains with fewer plant-beneficial properties is unknown. Here, we
tested the hypothesis that strains with higher numbers of plant-beneficial
properties would be preferentially selected by plant roots. To this end, the co
occurrence of 18 properties involved in enhanced plant nutrition, plant hormone
modulation, or pathogen inhibition was analyzed by molecular and biochemical
methods in a collection of maize rhizosphere and bulk soil isolates of
fluorescent Pseudomonas. Twelve plant-beneficial properties were found among the
698 isolates. Contrarily to expectation, maize preferentially selected
pseudomonads with low numbers of plant-beneficial properties (up to five). This
selection was not due to the predominance of strains with specific assortments of
these properties, or with specific taxonomic status. Therefore, the occurrence of
only few plant-beneficial properties appeared favorable for root colonization by
pseudomonads.
PMID- 27610111
TI - Garlic, from Remedy to Stimulant: Evaluation of Antifungal Potential Reveals
Diversity in Phytoalexin Allicin Content among Garlic Cultivars; Allicin
Containing Aqueous Garlic Extracts Trigger Antioxidants in Cucumber.
AB - Garlic has the charisma of a potent remedy and holds its repute of a therapeutic
panacea since the dawn of civilization. An integrated approach was adopted to
evaluate the genetic diversity among Chinese garlic cultivars for their
antifungal potency as well as allicin content distribution and, furthermore; a
bioassay was performed to study the bio-stimulation mechanism of aqueous garlic
extracts (AGE) in the growth and physiology of cucumber (Cucumis sativus).
Initially, 28 garlic cultivars were evaluated against four kinds of
phytopathogenic fungi; Fusarium oxysporum, Botrytis cinerea, Verticillium dahliae
and Phytophthora capsici, respectively. A capricious antifungal potential among
the selected garlic cultivars was observed. HPLC fingerprinting and
quantification confirmed diversity in allicin abundance among the selected
cultivars. Cultivar G025, G064, and G074 had the highest allicin content of 3.98,
3.7, and 3.66 mg g(-1), respectively, whereas G110 was found to have lowest
allicin content of 0.66 mg g(-1). Cluster analysis revealed three groups on the
basis of antifungal activity and allicin content among the garlic cultivars.
Cultivar G025, G2011-4, and G110 were further evaluated to authenticate the
findings through different solvents and shelf life duration and G025 had the
strongest antifungal activity in all conditions. minimum inhibitory concentration
and minimum fungicidal concentration of Allicin aqueous standard (AAS) and AGE
showed significant role of allicin as primary antifungal substance of AGE. Leaf
disk bioassay against P. capsici and V. dahliae to comparatively study direct
action of AGE and AAS during infection process employing eggplant and pepper
leaves showed a significant reduction in infection percentage. To study the
bioactivity of AGE, a bioassay was performed using cucumber seedlings and results
revealed that AGE is biologically active inside cucumber seedlings and alters the
defense mechanism of the plant probably activating reactive oxygen species at
mild concentrations. However, at higher concentrations, it might cause lipid
peroxidation and membrane damage which temper the growth of cucumber seedlings.
At the outcome of the study, an argument is advanced that current research
findings provide bases for cultivar selection in antifungal effectivity as well
as genetic variability of the cultivars. Allicin containing AGE can be used in
specialized horticultural situations such as plastic tunnel and organic farming
as a bio-stimulant to enhance cucumber growth and attenuate fungal degradation of
agricultural produce.
PMID- 27610113
TI - Metabolite Profiling Reveals a Specific Response in Tomato to Predaceous
Chrysoperla carnea Larvae and Herbivore(s)-Predator Interactions with the
Generalist Pests Tetranychus urticae and Myzus persicae.
AB - The spider mite Tetranychus urticae Koch and the aphid Myzus persicae (Sulzer)
both infest a number of economically significant crops, including tomato (Solanum
lycopersicum). Although used for decades to control pests, the impact of green
lacewing larvae Chrysoperla carnea (Stephens) on plant biochemistry was not
investigated. Here, we used profiling methods and targeted analyses to explore
the impact of the predator and herbivore(s)-predator interactions on tomato
biochemistry. Each pest and pest-predator combination induced a characteristic
metabolite signature in the leaf and the fruit thus, the plant exhibited a
systemic response. The treatments had a stronger impact on non-volatile
metabolites including abscisic acid and amino acids in the leaves in comparison
with the fruits. In contrast, the various biotic factors had a greater impact on
the carotenoids in the fruits. We identified volatiles such as myrcene and alpha
terpinene which were induced by pest-predator interactions but not by single
species, and we demonstrated the involvement of the phytohormone abscisic acid in
tritrophic interactions for the first time. More importantly, C. carnea larvae
alone impacted the plant metabolome, but the predator did not appear to elicit
particular defense pathways on its own. Since the presence of both C. carnea
larvae and pest individuals elicited volatiles which were shown to contribute to
plant defense, C. carnea larvae could therefore contribute to the reduction of
pest infestation, not only by its preying activity, but also by priming responses
to generalist herbivores such as T. urticae and M. persicae. On the other hand,
the use of C. carnea larvae alone did not impact carotenoids thus, was not
prejudicial to the fruit quality. The present piece of research highlights the
specific impact of predator and tritrophic interactions with green lacewing
larvae, spider mites, and aphids on different components of the tomato primary
and secondary metabolism for the first time, and provides cues for further in
depth studies aiming to integrate entomological approaches and plant
biochemistry.
PMID- 27610112
TI - Photosynthate Regulation of the Root System Architecture Mediated by the
Heterotrimeric G Protein Complex in Arabidopsis.
AB - Assimilate partitioning to the root system is a desirable developmental trait to
control but little is known of the signaling pathway underlying partitioning. A
null mutation in the gene encoding the Gbeta subunit of the heterotrimeric G
protein complex, a nexus for a variety of signaling pathways, confers altered
sugar partitioning in roots. While fixed carbon rapidly reached the roots of wild
type and agb1-2 mutant seedlings, agb1 roots had more of this fixed carbon in the
form of glucose, fructose, and sucrose which manifested as a higher lateral root
density. Upon glucose treatment, the agb1-2 mutant had abnormal gene expression
in the root tip validated by transcriptome analysis. In addition, PIN2 membrane
localization was altered in the agb1-2 mutant. The heterotrimeric G protein
complex integrates photosynthesis-derived sugar signaling incorporating both
membrane-and transcriptional-based mechanisms. The time constants for these
signaling mechanisms are in the same range as photosynthate delivery to the root,
raising the possibility that root cells are able to use changes in carbon
fixation in real time to adjust growth behavior.
PMID- 27610114
TI - Environmental and Genetic Factors Associated with Solanesol Accumulation in
Potato Leaves.
AB - Solanesol is a high value 45-carbon, unsaturated, all-trans-nonaprenol
isoprenoid. Recently solanesol has received particular attention because of its
utility, both in its own right and as a precursor in the production of numerous
compounds used in the treatment of disease states. Solanesol is found mainly in
solanaceous crops such as potato, tomato, tobacco and pepper where it accumulates
in the foliage. There is considerable potential to explore the extraction of
solanesol from these sources as a valuable co-product. In this study we have
characterized the genetic variation in leaf solanesol content in a biparental,
segregating diploid potato population. We demonstrate that potato leaf solanesol
content is genetically controlled and identify several quantitative trait loci
associated with leaf solanesol content. Transient over-expression of genes from
the methylerythritol 4-phosphate (MEP) and mevalonic acid (MVA) pathways, either
singly or in combination, resulted in enhanced accumulation of solanesol in
leaves of Nicotiana benthamiana, providing insights for genetically engineering
the pathway. We also demonstrate that in potato, leaf solanesol content is
enhanced by up to six-fold on exposure to moderately elevated temperature and
show corresponding changes in expression patterns of MEP and MVA genes. Our
combined approaches offer new insights into solanesol accumulation and strategies
for developing a bio-refinery approach to potato production.
PMID- 27610115
TI - Insights into the Indian Peanut Genotypes for ahFAD2 Gene Polymorphism Regulating
Its Oleic and Linoleic Acid Fluxes.
AB - In peanut (Arachis hypogaea L.), the customization of fatty acid profile is an
evolving area to fulfill the nutritional needs in the modern market. A total of
174 peanut genotypes, including 167 Indian cultivars, 6 advanced breeding lines
and "SunOleic95R"-a double mutant line, were investigated using AS-PCRs, CAPS and
gene sequencing for the ahFAD2 allele polymorphism, along with its fatty acid
compositions. Of these, 80 genotypes were found having substitution (448G>A)
mutation only in ahFAD2A gene, while none recorded 1-bp insertion (441_442insA)
mutation in ahFAD2B gene. Moreover, 22 wild peanut accessions found lacking both
the mutations. Among botanical types, the ahFAD2A mutation was more frequent in
ssp. hypogaea (89%) than in ssp. fastigiata (17%). This single allele mutation,
found affecting not only oleic to linoleic acid fluxes, but also the composition
of other fatty acids in the genotypes studied. Repeated use of a few selected
genotypes in the Indian varietal development programs were also eminently
reflected in its ahFAD2 allele polymorphism. Absence of known mutations in the
wild-relatives indicated the possible origin of these mutations, after the
allotetraploidization of cultivated peanut. The SNP analysis of both ahFAD2A and
ahFAD2B genes, revealed haplotype diversity of 1.05% and 0.95%, while Ka/Ks ratio
of 0.36 and 0.39, respectively, indicating strong purifying selection pressure on
these genes. Cluster analysis, using ahFAD2 gene SNPs, showed presence of both
mutant and non-mutant genotypes in the same cluster, which might be due the
presence of ahFAD2 gene families. This investigation provided insights into the
large number of Indian peanut genotypes, covering various aspects related to O/L
flux regulation and ahFAD2 gene polymorphism.
PMID- 27610116
TI - Screening of Bread Wheat Genotypes for Drought Tolerance Using Phenotypic and
Proline Analyses.
AB - Drought stress is one of the leading constraints to wheat (Triticum aestivum L.)
production globally. Breeding for drought tolerance using novel genetic resources
is an important mitigation strategy. This study aimed to determine the level of
drought tolerance among diverse bread wheat genotypes using agronomic traits and
proline analyses and to establish correlation of proline content and agronomic
traits under drought-stress conditions in order to select promising wheat lines
for breeding. Ninety-six diverse genotypes including 88 lines from the
International Maize and Wheat Improvement Center (CIMMYT)'s heat and drought
nurseries, and eight local checks were evaluated under greenhouse and field
conditions during 2014/15 and 2015/16 making four testing environments. The
following phenotypic traits were collected after stress imposed during the
heading to anthesis period: the number of days to heading (DTH), days to maturity
(DTM), productive tiller number (TN), plant height (PH), spike length (SL),
spikelet per spike (SPS), kernels per spike (KPS), thousand kernel weight (TKW)
and grain yield (GY) and proline content (PC). Analysis of variance, Pearson's
correlation coefficient, principal component and stress tolerance index were
calculated. Genotypes with high yield performance under stressed and optimum
conditions maintained high values for yield components. Proline content
significantly increased under stress, but weakly correlated with agronomic traits
under both optimal and water limited conditions. The positive correlation
observed between grain yield and proline content under-drought stress conditions
provides evidence that proline accumulation might ultimately be considered as a
tool for effective selection of drought tolerant genotypes. The study selected 12
genotypes with high grain yields under drought stressed conditions and favorable
adaptive traits useful for breeding.
PMID- 27610117
TI - The Maize Divergent spindle-1 (dv1) Gene Encodes a Kinesin-14A Motor Protein
Required for Meiotic Spindle Pole Organization.
AB - The classic maize mutant divergent spindle-1 (dv1) causes failures in meiotic
spindle assembly and a decrease in pollen viability. By analyzing two independent
dv1 alleles we demonstrate that this phenotype is caused by mutations in a member
of the kinesin-14A subfamily, a class of C-terminal, minus-end directed
microtubule motors. Further analysis demonstrates that defects in early spindle
assembly are rare, but that later stages of spindle organization promoting the
formation of finely focused spindle poles are strongly dependent on Dv1. Anaphase
is error-prone in dv1 lines but not severely so, and the majority of cells show
normal chromosome segregation. Live-cell imaging of wild type and mutant plants
carrying CFP-tagged beta-tubulin confirm that meiosis in dv1 lines fails
primarily at the pole-sharpening phase of spindle assembly. These data indicate
that plant kinesin-14A proteins help to enforce bipolarity by focusing spindle
poles and that this stage of spindle assembly is not required for transition
through the spindle checkpoint but improves the accuracy of chromosome
segregation.
PMID- 27610119
TI - Advances in the Pathogenesis, Diagnosis and Treatment of Bow Hunter's Syndrome: A
Comprehensive Review of the Literature.
AB - Bow hunter's syndrome (BHS), also known as rotational vertebral artery (VA)
occlusion syndrome, is a rare yet treatable type of symptomatic vertebrobasilar
insufficiency resulting from mechanical occlusion or stenosis of the VA during
head and neck rotation or extension. The symptoms of BHS range from transient
vertigo to posterior circulation stroke. The underlying pathology is dynamic
stenosis or compression of the VA by abnormal bony structures with neck rotation
or extension in many cases, such as osteophyte, disc herniation, cervical
spondylosis, tendinous bands or tumors. Imaging approaches, such as Doppler
sonography, computed tomography and angiography, as well as magnetic resonance
imaging and angiography, are widely used in the diagnosis and evaluation of this
syndrome. Digital subtraction angiography with head rotation remains the gold
standard diagnostic method. Conservative management, surgery and endovascular
procedures are the three major treatment methods for BHS, whereas some
symptomatic patients may need operative treatment including surgery and
endovascular procedures when conservative management is not adequate.
PMID- 27610118
TI - Society of Vascular and Interventional Neurology (SVIN) Stroke Interventional
Laboratory Consensus (SILC) Criteria: A 7M Management Approach to Developing a
Stroke Interventional Laboratory in the Era of Stroke Thrombectomy for Large
Vessel Occlusions.
AB - Brain attack care is rapidly evolving with cutting-edge stroke interventions
similar to the growth of heart attack care with cardiac interventions in the last
two decades. As the field of stroke intervention is growing exponentially
globally, there is clearly an unmet need to standardize stroke interventional
laboratories for safe, effective, and timely stroke care. Towards this goal, the
Society of Vascular and Interventional Neurology (SVIN) Writing Committee has
developed the Stroke Interventional Laboratory Consensus (SILC) criteria using a
7M management approach for the development and standardization of each stroke
interventional laboratory within stroke centers. The SILC criteria include: (1)
manpower: personnel including roles of medical and administrative directors,
attending physicians, fellows, physician extenders, and all the key stakeholders
in the stroke chain of survival; (2) machines: resources needed in terms of
physical facilities, and angiography equipment; (3) materials: medical device
inventory, medications, and angiography supplies; (4) methods: standardized
protocols for stroke workflow optimization; (5) metrics (volume): existing
credentialing criteria for facilities and stroke interventionalists; (6) metrics
(quality): benchmarks for quality assurance; (7) metrics (safety): radiation and
procedural safety practices.
PMID- 27610120
TI - Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized
Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke
Treatment after 20 Years.
AB - BACKGROUND: Recent advances in the treatment of ischemic stroke have focused on
revascularization and led to better clinical and functional outcomes. A
systematic review and pooled analyses of 6 recent multicentered prospective
randomized controlled trials (MPRCT) were performed to compare intravenous tissue
plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV
tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to
large vessel occlusion (LVO). OBJECTIVES: Six MPRCTs (MR CLEAN, ESCAPE, EXTEND
IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were
selected for assessing the following: (1) prespecified primary clinical outcomes
of AIS patients in intervention and control arms: good outcomes were defined by a
modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes
were: (a) revascularization rates [favorable outcomes defined as modified
Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic
intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number
needed to harm (NNH), number needed to treat (NNT), and relative percent
difference (RPD) between intervention and control groups, and (d) random effects
model to determine overall significance (forest and funnel plots). RESULTS: A
total of 1,386 patients were included. Good outcomes at 90 days were seen in 46%
of patients in the intervention (p < 0.00001) and in 27% of patients in the
control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of
patients in the intervention arm. The sICH and mortality in the intervention arm
compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%,
respectively. The NNT and NNH in the intervention and control groups were 5.3 and
9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better
chance of achieving a good 90-day outcome as compared to controls. CONCLUSIONS:
Endovascular therapy combined with IV tPA (in appropriately selected patients)
for LVO-related AIS is superior to IV tPA alone. These results support
establishing an endovascular therapy in addition to IV tPA as the standard of
care for AIS secondary to LVO.
PMID- 27610122
TI - Consecutive Endovascular Treatment of 20 Ruptured Very Small (<3 mm) Anterior
Communicating Artery Aneurysms.
AB - BACKGROUND: Small aneurysms located at the anterior communicating artery carry
significant procedural challenges due to a complex anatomy. Recent advances in
endovascular technologies have expanded the use of coil embolization for small
aneurysm treatment. However, limited reports describe their safety and efficacy
profiles in very small anterior communicating artery aneurysms. OBJECTIVE: We
sought to review and report the immediate and long-term clinical as well as
radiographic outcomes of consecutive patients with ruptured very small anterior
communicating artery aneurysms treated with current endovascular coil
embolization techniques. METHODS: A prospectively maintained single-institution
neuroendovascular database was accessed to identify consecutive cases of very
small (<3 mm) ruptured anterior communicating artery aneurysms treated
endovascularly between 2006 and 2013. RESULTS: A total of 20 patients with
ruptured very small (<3 mm) anterior communicating artery aneurysms were
consecutively treated with coil embolization. The average maximum diameter was
2.66 +/- 0.41 mm. Complete aneurysm occlusion was achieved for 17 (85%) aneurysms
and near-complete aneurysm occlusion for 3 (15%) aneurysms. Intraoperative
perforation was seen in 2 (10%) patients without any clinical worsening or need
for an external ventricular drain. A thromboembolic event occurred in 1 (5 %)
patient without clinical worsening or radiologic infarct. Median clinical follow
up was 12 (+/-14.1) months and median imaging follow-up was 12 (+/-18.4) months.
CONCLUSION: This report describes the largest series of consecutive endovascular
treatments of ruptured very small anterior communicating artery aneurysms. These
findings suggest that coil embolization of very small aneurysms in this location
can be performed with acceptable rates of complications and recanalization.
PMID- 27610124
TI - Endovascular Management of Sigmoid Sinus Diverticulum.
AB - Sigmoid sinus diverticulum (SSD) is a rare vascular disorder due to dehiscence of
the sigmoid plate. It may be associated with prediverticular venous sinus
stenosis (SS) and usually presents as pulsatile tinnitus. The mechanism of
development of the SSD and tinnitus from a sinus diverticulum and associated SS
is unclear. Previous case reports have suggested that remodeling of the venous
system targeting the stenosis, elimination of the diverticulum, or both, have
resulted in symptom relief. We present a case of SSD with SS, treated by stenting
of the stenosis along with coil embolization of the diverticulum, resulting in
complete relief of symptoms. We have also reviewed the literature and discussed
the evolution of management from open surgical treatment to endovascular
treatment.
PMID- 27610123
TI - Fractional Flow Assessment for the Evaluation of Intracranial Atherosclerosis: A
Feasibility Study.
AB - PURPOSE: Current studies on endovascular intervention for intracranial
atherosclerosis select patients based on luminal stenosis. Coronary studies
demonstrated that fractional flow measurements assess ischemia better than
anatomical stenosis and can guide patient selection for intervention. We
similarly postulated that fractional flow can be used to assess ischemic stroke
risk. METHODS: This was a feasibility study to assess the technical use and
safety of applying a pressure guidewire to measure fractional flow across
intracranial stenoses. Twenty patients with severe intracranial stenosis were
recruited. The percentage of luminal stenosis, distal to proximal pressure ratios
(fractional flow) and the fractional flow gradients across the stenosis were
measured. Procedural success rate and safety outcomes were documented. RESULTS:
All 20 patients had successful crossing of stenosis by the pressure guidewire.
Ten patients underwent angioplasty, and 5 had stenting performed. There was one
perforator stroke, but not related to the use of the pressure wire. For the 13
patients with complete pre- and postintervention data, the mean preintervention
stenosis, fractional flow and translesional pressure gradient were 76.2%, 0.66
and 29.9 mm Hg, whilst the corresponding postintervention measurements were
24.7%, 0.88 and 10.9 mm Hg, respectively. Fractional flow (r = -0.530, p = 0.001)
and the translesional pressure gradient (r = 0.501, p = 0.002) only had a modest
correlation with the luminal stenosis. CONCLUSION: Fractional flow measurement by
floating a pressure guidewire across the intracranial stenosis was technically
feasible and safe in this study. Further studies are needed to validate its use
for ischemic stroke risk assessment.
PMID- 27610121
TI - Training Guidelines for Endovascular Stroke Intervention: An International Multi
Society Consensus Document.
PMID- 27610125
TI - Automated CT Perfusion for Ischemic Core Volume Prediction in Tandem Anterior
Circulation Occlusions.
AB - BACKGROUND/AIM: CT perfusion (CTP) predicts ischemic core volumes in acute
ischemic stroke (AIS); however, assumptions made within the pharmacokinetic model
may engender errors by the presence of tracer delay or dispersion. We aimed to
evaluate the impact of hemodynamic disturbance due to extracranial anterior
circulation occlusions upon the accuracy of ischemic core volume estimation with
an automated perfusion analysis tool (RAPID) among AIS patients with large-vessel
occlusions. METHODS: A prospectively collected, interventional database was
retrospectively reviewed for all cases of endovascular treatment of AIS between
September 2010 and March 2015 for patients with anterior circulation occlusions
with baseline CTP and full reperfusion (mTICI3). RESULTS: Out of 685 treated
patients, 114 fit the inclusion criteria. Comparison between tandem (n = 21) and
nontandem groups (n = 93) revealed similar baseline ischemic core (20 +/- 19 vs.
19 +/- 25 cm(3); p = 0.8), Tmax >6 s (175 +/- 109 vs. 162 +/- 118 cm(3); p =
0.6), Tmax >10 s (90 +/- 84 vs. 90 +/- 91 cm(3); p = 0.9), and final infarct
volumes (45 +/- 47 vs. 37 +/- 45 cm(3); p = 0.5). Baseline core volumes were
found to correlate with final infarct volumes for the tandem (r = 0.49; p = 0.02)
and nontandem (r = 0.44; p < 0.01) groups. The mean absolute difference between
estimated core and final infarct volume was similar between patients with and
those without (24 +/- 41 vs. 17 +/- 41 cm(3); p = 0.5) tandem lesions.
CONCLUSIONS: The prediction of baseline ischemic core volumes through an
optimized CTP analysis employing rigorous normalization, thresholding, and voxel
wise analysis is not significantly influenced by the presence of underlying
extracranial carotid steno-occlusive disease in large-vessel AIS.
PMID- 27610127
TI - Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian
network.
AB - By 2050, it is estimated that the number of worldwide Alzheimer's disease (AD)
patients will quadruple from the current number of 36 million, while no proven
disease-modifying treatments are available. At present, the underlying disease
mechanisms remain under investigation, and recent studies suggest that the
disease involves multiple etiological pathways. To better understand the disease
and develop treatment strategies, a number of ongoing studies including the
Alzheimer's Disease Neuroimaging Initiative (ADNI) enroll many study participants
and acquire a large number of biomarkers from various modalities including
demographic, genotyping, fluid biomarkers, neuroimaging, neuropsychometric test,
and clinical assessments. However, a systematic approach that can integrate all
the collected data is lacking. The overarching goal of our study is to use
machine learning techniques to understand the relationships among different
biomarkers and to establish a system-level model that can better describe the
interactions among biomarkers and provide superior diagnostic and prognostic
information. In this pilot study, we use Bayesian network (BN) to analyze
multimodal data from ADNI, including demographics, volumetric MRI, PET,
genotypes, and neuropsychometric measurements and demonstrate our approach to
have superior prediction accuracy.
PMID- 27610128
TI - Deep Convolutional Extreme Learning Machine and Its Application in Handwritten
Digit Classification.
AB - In recent years, some deep learning methods have been developed and applied to
image classification applications, such as convolutional neuron network (CNN) and
deep belief network (DBN). However they are suffering from some problems like
local minima, slow convergence rate, and intensive human intervention. In this
paper, we propose a rapid learning method, namely, deep convolutional extreme
learning machine (DC-ELM), which combines the power of CNN and fast training of
ELM. It uses multiple alternate convolution layers and pooling layers to
effectively abstract high level features from input images. Then the abstracted
features are fed to an ELM classifier, which leads to better generalization
performance with faster learning speed. DC-ELM also introduces stochastic pooling
in the last hidden layer to reduce dimensionality of features greatly, thus
saving much training time and computation resources. We systematically evaluated
the performance of DC-ELM on two handwritten digit data sets: MNIST and USPS.
Experimental results show that our method achieved better testing accuracy with
significantly shorter training time in comparison with deep learning methods and
other ELM methods.
PMID- 27610126
TI - Aneurysm Study of Pipeline in an Observational Registry (ASPIRe).
AB - BACKGROUND AND OBJECTIVE: Few prospective studies exist evaluating the safety and
efficacy of the Pipeline Embolization Device (PED) in the treatment of
intracranial aneurysms. The Aneurysm Study of Pipeline In an observational
Registry (ASPIRe) study prospectively analyzed rates of complete aneurysm
occlusion and neurologic adverse events following PED treatment of intracranial
aneurysms. MATERIALS AND METHODS: We performed a multicenter study prospectively
evaluating patients with unruptured intracranial aneurysms treated with PED.
Primary outcomes included (1) spontaneous rupture of the Pipeline-treated
aneurysm; (2) spontaneous nonaneurysmal intracranial hemorrhage (ICH); (3) acute
ischemic stroke; (4) parent artery stenosis, and (5) permanent cranial
neuropathy. Secondary endpoints were (1) treatment success and (2) morbidity and
mortality at the 6-month follow-up. Vascular imaging was evaluated at an
independent core laboratory. RESULTS: One hundred and ninety-one patients with
207 treated aneurysms were included in this registry. The mean aneurysm size was
14.5 +/- 6.9 mm, and the median imaging follow-up was 7.8 months. Twenty-four
aneurysms (11.6%) were small, 162 (78.3%) were large and 21 (10.1%) were giant.
The median clinical follow-up time was 6.2 months. The neurological morbidity
rate was 6.8% (13/191), and the neurological mortality rate was 1.6% (3/191). The
combined neurological morbidity/mortality rate was 6.8% (13/191). The most common
adverse events were ischemic stroke (4.7%, 9/191) and spontaneous ICH (3.7%,
7/191). The complete occlusion rate at the last follow-up was 74.8% (77/103).
CONCLUSIONS: Our prospective postmarket study confirms that PED treatment of
aneurysms in a heterogeneous patient population is safe with low rates of
neurological morbidity and mortality. Patients with angiographic follow-up had
complete occlusion rates of 75% at 8 months.
PMID- 27610129
TI - A New Artificial Neural Network Approach in Solving Inverse Kinematics of Robotic
Arm (Denso VP6242).
AB - This paper presents a novel inverse kinematics solution for robotic arm based on
artificial neural network (ANN) architecture. The motion of robotic arm is
controlled by the kinematics of ANN. A new artificial neural network approach for
inverse kinematics is proposed. The novelty of the proposed ANN is the inclusion
of the feedback of current joint angles configuration of robotic arm as well as
the desired position and orientation in the input pattern of neural network,
while the traditional ANN has only the desired position and orientation of the
end effector in the input pattern of neural network. In this paper, a six DOF
Denso robotic arm with a gripper is controlled by ANN. The comprehensive
experimental results proved the applicability and the efficiency of the proposed
approach in robotic motion control. The inclusion of current configuration of
joint angles in ANN significantly increased the accuracy of ANN estimation of the
joint angles output. The new controller design has advantages over the existing
techniques for minimizing the position error in unconventional tasks and
increasing the accuracy of ANN in estimation of robot's joint angles.
PMID- 27610130
TI - Prognostic Impact of mRNA Expression Levels of HER1-4 (ERBB1-4) in Patients with
Locally Advanced Rectal Cancer.
AB - Background. No predictive or prognostic biomarker is available for patients with
locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy
(CRT). Members of the human epidermal growth factor receptor (HER) family of
receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and
HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was
performed to assess expression levels and study the potential prognostic impact
for disease-free and overall survival in patients with LARC. Patients and
Methods. ERBB1-4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA
were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from
86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based
CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and
HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients
with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk
for recurrence and death. Patients with high mRNA expression of MKI67 had reduced
risk for relapse. Conclusion. This analysis suggests a prognostic impact of both
ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or
fluorouracil-based chemoradiotherapy.
PMID- 27610132
TI - Giant Serous Cystadenoma of the Pancreas (?10 cm): The Clinical Features and CT
Findings.
AB - Purpose. To report the clinical features and CT manifestations of giant
pancreatic serous cystadenoma (>=10 cm). Methods. We retrospectively reviewed the
clinical features and CT findings of 6 cases of this entity. Results. All 6
patients were symptomatic. The tumors were 10.2 cm-16.5 cm (median value, 13.0
cm). CT imaging revealed that all 6 cases showed microcystic appearances (n = 5)
or mixed microcystic and macrocystic appearances (n = 1). Five patients with
tumors at the distal end of the pancreas received distal pancreatectomy. Among
these 5 patients, 2 patients underwent partial transverse colon resection or
omentum resection due to close adhesion. One patient whose tumor was located in
the pancreatic head underwent pancreaticoduodenectomy; however, due to encasement
of the portal and superior mesenteric veins, the tumor was incompletely resected.
One patient had abundant draining veins on the tumor surface and suffered large
blood loss (700 mL). After 6-49 months of follow-up the 6 patients showed no
tumor recurrence or signs of malignant transformation. Conclusions. Giant
pancreatic serous cystadenoma necessitates surgical resection due to large size,
symptoms, uncertain diagnosis, and adjacent organ compression. The relationship
between the tumors and the neighboring organs needs to be carefully assessed
before operation on CT image.
PMID- 27610131
TI - The Diagnostic Accuracy of Linear Endoscopic Ultrasound for Evaluating Symptoms
Suggestive of Common Bile Duct Stones.
AB - Background. In order to assess the diagnostic accuracy of linear EUS for
evaluating clinically suggestive CBD stones in high-risk groups. Methods. 202
patients with clinically suggestive CBD stones in high-risk groups who underwent
linear EUS examination between January 2012 and January 2015 were retrospectively
reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) with stone
extraction or surgical choledochoscopy was only performed when a CBD stone was
detected by linear EUS. Cases that were negative for CBD stones were followed up
for at least 6 months. Results. Of 202 enrolled patients, 126 were positive for
CBD stones according to linear EUS findings. 124 patients successfully underwent
ERCP, and ERCP failed in 2 who were later successfully treated by surgical
intervention. There were 2 false-positive cases with positive findings for CBD
stones on ERCP. Among 76 patients without CBD stones, no false-negative cases
were identified during the mean 6-month follow-up. Linear EUS had sensitivity,
specificity, and positive and negative predictive values for the detection of CBD
stones of 100%, 92.88%, 98.21%, and 100%, respectively. Conclusions. Linear EUS
is a safe and efficacious diagnostic tool for evaluating clinically suggestive
CBD stones with high risk of choledocholithiasis. Performing linear EUS prior to
ERCP in patients with symptoms suggestive of CBD stones can reduce unnecessary
ERCP procedures.
PMID- 27610133
TI - Length of Stay in Ambulatory Surgical Oncology Patients at High Risk for Sleep
Apnea as Predicted by STOP-BANG Questionnaire.
AB - Background. The STOP-BANG questionnaire has been used to identify surgical
patients at risk for undiagnosed obstructive sleep apnea (OSA) by classifying
patients as low risk (LR) if STOP-BANG score < 3 or high risk (HR) if STOP-BANG
score >= 3. Few studies have examined whether postoperative complications are
increased in HR patients and none have been described in oncologic patients.
Objective. This retrospective study examined if HR patients experience increased
complications evidenced by an increased length of stay (LOS) in the
postanesthesia care unit (PACU). Methods. We retrospectively measured LOS and the
frequency of oxygen desaturation (<93%) in cancer patients who were given the
STOP-BANG questionnaire prior to cystoscopy for urologic disease in an ambulatory
surgery center. Results. The majority of patients in our study were men (77.7%),
over the age of 50 (90.1%), and had BMI < 30 kg/m(2) (88.4%). STOP-BANG results
were obtained on 404 patients. Cumulative incidence of the time to discharge
between HR and the LR groups was plotted. By 8 hours, LR patients showed a higher
cumulative probability of being discharged early (80% versus 74%, P = 0.008).
Conclusions. Urologic oncology patients at HR for OSA based on the STOP-BANG
questionnaire were less likely to be discharged early from the PACU compared to
LR patients.
PMID- 27610135
TI - Endobronchial Carcinoid Tumour with Extensive Ossification: An Unusual Case
Presentation.
AB - Carcinoid tumour is a well-known primary endobronchial lung neoplasm. Although
calcifications may be seen in up to 30% of pulmonary carcinoid tumours, near
complete ossification of these tumours is an unusual finding. Such lesions can
prove diagnostically challenging at the time of intraoperative frozen section as
the latter technique requires thin sectioning of the lesion for microscopic
assessment. We present an unusual case of endobronchial carcinoid tumour with
extensive ossification in a 45-year-old male. Preliminary intraoperative
diagnosis was achieved through the alternative use of cytology scrape smears. The
final diagnosis was confirmed after decalcification of the tumour. The prognostic
implications of heavily ossified carcinoid tumours remain elusive. Long-term
clinical follow-up of these patients is recommended.
PMID- 27610134
TI - Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa
Powder in Sprague-Dawley Rats.
AB - Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of
compressed solid blocks which remains after extraction. Little scientific data is
available concerning its safety despite the presence of potential toxic elements.
Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral
high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g)
by the limit test method. One group received water and the test group 2000 mg/kg
UNCP. All animals were observed for 14 days and then euthanized for
haematological, biochemical, and histopathological examinations. Thirty-eight
(38) elements were found in UNCP. There was an increase in HDL cholesterol (p <
0.05), reduction in LDL cholesterol (p > 0.05), alkaline phosphatase (p < 0.05),
and creatinine levels, and slight increase in urea levels (p > 0.05).
Haematological changes were not significant. Histopathological analysis showed no
toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal
erosion was observed in the test group. UNCP appears to be relatively safe when
taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should
however be exercised at high doses due to the high elemental content of copper
and high possibility of intestinal lining erosion.
PMID- 27610136
TI - Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol
Withdrawal: A Blurred Clinical Horizon.
AB - Central pontine myelinolysis (CPM), a potentially fatal and debilitating
neurological condition, was first described in 1959 in a study on alcoholic and
malnourished patients. It is a condition most frequently related to rapid
correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign
with a favorable prognosis compared to CPM secondary to rapid correction of
hyponatremia. We describe a normonatremic, alcoholic patient who presented with
CPM after a rapid rise in his sodium levels. Our case illustrates the fact that
CPM can manifest even in patients who are normonatremic at baseline. Rapid rises
in sodium levels should be promptly reversed before clinical symptoms manifest in
patient with risk factors for CPM irrespective of their baseline sodium levels.
Furthermore, clinical evolution of CPM can be difficult to discern from the
natural course of alcohol withdrawal delirium, requiring astuteness and
maintenance of a high degree of clinical suspicion on the part of the physician.
PMID- 27610137
TI - In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal
Stem Cells in Normal Rats through Bioluminescence Imaging.
AB - Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for
multiple types of disease short of effective treatment. Dozens of clinical trials
published demonstrated strikingly positive therapeutic effects of MSCs. However,
as a specific agent, little research has focused on the dynamic distribution of
MSCs after in vivo administration. In this study, we track systemically
transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats
through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging,
immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological
distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin
apart from the lungs and kidneys after tail vein injection and could not be
detected 14 days later. Allogeneic BMSCs mainly appeared not at the
parenchymatous organs but at the subepidermal connective tissue and adipose
tissue in healthy rats. There were no significant MSCs-related adverse effects
except for transient decrease in neutrophils. These findings will provide
experimental evidences for a better understanding of the biocharacteristics of
BMSCs.
PMID- 27610138
TI - tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor
Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis.
AB - We examined the role of tissue plasminogen activator- (tPA-) matrix
metalloproteinase- (MMP-) 9 in mobilizing endothelial progenitor cells (EPCs)
from bone marrow to circulation and critical limb ischemia (CLI) region. Male
C57BL/6J mice having been irradiated were categorized into wild-type mice (WT)
receiving WT bone marrow cell (BMC) transfusion (group 1), WT mice receiving MMP
9 knockout (MMP-9(-/-)) BMC (group 2), MMP-9(-/-) receiving MMP-9(-/-) BMC (group
3), and MMP-9(-/-) receiving WT BMC (group 4), each of which was subdivided into
sham control (SC), CLI, SC-tPA, and CLI-tPA. In groups 1 and 4, by post-CLI 18 h
and day 14, circulating EPC (C-kit+/CD31+, Sca-1+/KDR+) levels were highest in
CLI-tPA subgroup. In groups 2 and 3, EPC levels did not differ among all
subgroups. The EPC levels in bone marrow were higher in groups 2 and 3 than those
in groups 1 and 4. By day 14, in animals with CLI, expression levels of
proangiogenic factors (CXCR4, SDF-1alpha, and VEGF) showed similar trends as
circulating EPC levels. Moreover, the number of infiltrated neutrophils and
macrophages in quadriceps was higher in groups 1 and 4 than groups in 2 and 3. In
conclusion, tPA-MMP-9 axis plays a crucial role in EPC mobilization and
angiogenesis in experimental CLI.
PMID- 27610140
TI - Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative
Potential In Vitro.
AB - Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet
little is known regarding their interaction with the microenvironment. Signaling
cues present in the microenvironment change with development and disease. This
work aims to assess the influence of two distinct signaling moieties on CPCs:
cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for
improving CPC therapy: paracrine signaling, proliferation, connexin43 expression,
and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was
secreted by CPCs cultured on fibronectin and collagen I. The application of
mechanical strain increased vascular endothelial growth factor A secretion 2-4
fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac
extracellular matrix. CPC proliferation was at least 25% higher on fibronectin
than that on other matrices, especially for lower strain magnitudes. At 5%
strain, connexin43 expression was highest on fibronectin. With increasing strain
magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on
collagen I and a naturally derived cardiac extracellular matrix. Cyclic
mechanical strain induced the strongest CPC alignment when cultured on
fibronectin or collagen I. This study demonstrates that culturing CPCs on
fibronectin with 5% strain magnitude is optimal for their vascular endothelial
growth factor A secretion, proliferation, connexin43 expression, and alignment.
PMID- 27610141
TI - Comparison of Osteogenesis between Adipose-Derived Mesenchymal Stem Cells and
Their Sheets on Poly-epsilon-Caprolactone/beta-Tricalcium Phosphate Composite
Scaffolds in Canine Bone Defects.
AB - Multipotent mesenchymal stem cells (MSCs) and MSC sheets have effective
potentials of bone regeneration. Composite polymer/ceramic scaffolds such as poly
epsilon-caprolactone (PCL)/beta-tricalcium phosphate (beta-TCP) are widely used
to repair large bone defects. The present study investigated the in vitro
osteogenic potential of canine adipose-derived MSCs (Ad-MSCs) and Ad-MSC sheets.
Composite PCL/beta-TCP scaffolds seeded with Ad-MSCs or wrapped with osteogenic
Ad-MSC sheets (OCS) were also fabricated and their osteogenic potential was
assessed following transplantation into critical-sized bone defects in dogs. The
alkaline phosphatase (ALP) activity of osteogenic Ad-MSCs (O-MSCs) and OCS was
significantly higher than that of undifferentiated Ad-MSCs (U-MSCs). The ALP,
runt-related transcription factor 2, osteopontin, and bone morphogenetic protein
7 mRNA levels were upregulated in O-MSCs and OCS as compared to U-MSCs. In a
segmental bone defect, the amount of newly formed bone was greater in PCL/beta
TCP/OCS and PCL/beta-TCP/O-MSCs/OCS than in the other groups. The OCS exhibit
strong osteogenic capacity, and OCS combined with a PCL/beta-TCP composite
scaffold stimulated new bone formation in a critical-sized bone defect. These
results suggest that the PCL/beta-TCP/OCS composite has potential clinical
applications in bone regeneration and can be used as an alternative treatment
modality in bone tissue engineering.
PMID- 27610139
TI - The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in
Hepatocellular Carcinoma.
AB - Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized
by liver cancer stem cells (LCSCs), which are a subset of cells with "stem-like"
characteristics. Identification of the LCSCs is a fundamental and important
problem in HCC research. LCSCs have been investigated by various stem cell
biomarkers. There is still lack of consensus regarding the existence of a
"global" marker for LCSCs in HCC. In this review article, we summarize the
progress and prospects of putative biomarkers for LCSCs in the past decades,
which is essential to develop future therapies targeting CSCs and to predict
prognosis and curative effect of these therapies.
PMID- 27610143
TI - Medicinal Food Products; a New Approach from Ordinary Foods to Medicine.
PMID- 27610142
TI - Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal
Cells.
AB - Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions,
including differentiation into skeletal cells (progenitor function),
hematopoiesis support, and immune regulation (nonprogenitor function). We have
previously demonstrated the presence of morphological and functional
heterogeneity of hBMSC cultures. In the present study, we characterized in detail
two hTERT-BMSC clonal cell populations termed here CL1 and CL2 that represent an
opposing phenotype with respect to morphology, markers expression: alkaline
phosphatase (ALP) and CD146, and ex vivo differentiation potential. CL1
differentiated readily to osteoblasts, adipocytes, and chondrocytes as shown by
expression of lineage specific genes and proteins. Whole genome transcriptome
profiling of CL1 versus CL2 revealed enrichment in CL1 of bone-, mineralization-,
and skeletal muscle-related genes, for example, ALP, POSTN, IGFBP5 BMP4, and
CXCL12. On the other hand, CL2 transcriptome was enriched in immune modulatory
genes, for example, CD14, CD99, NOTCH3, CXCL6, CFB, and CFI. Furthermore, gene
expression microarray analysis of osteoblast differentiated CL1 versus CL2 showed
significant upregulation in CL1 of bone development and osteoblast
differentiation genes which included several homeobox genes: TBX15, HOXA2 and
HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based
downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic
differentiation. Our studies demonstrate the existence of molecular and
functional heterogeneity in cultured hBMSC. ALP can be employed to identify
osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures.
PMID- 27610144
TI - Norfloxacin Loaded pH Triggered Nanoparticulate in-situ Gel for Extraocular
Bacterial Infections: Optimization, Ocular Irritancy and Corneal Toxicity.
AB - In order to achieve prolong corneal contact time of norfloxacin (NFX) for
treatment of extra ocular diseases, a pH triggered nanoparticulate in-situ
gelling system was designed to explore dual advantage of nanoparticles and in
situ gelling system, for its ocular delivery. NFX loaded nanocarriers were
developed by ionotropic gelation technique using chitosan as a matrix forming
polymer, cross-linked by an anionic crosslinker sodium tripolyphosphate (TPP).
Optimization of nanoformulations was done by 3(2) full factorial design using
chitosan and TPP concentration(s) as the independent variables and particle size,
% entrapment efficiency and % cumulative drug release as the responses. The
experimental design was validated by extra design check point formulation (N10).
The optimized formulation (N4) selected on the basis of highest desirability
factor (0.895) was developed as in-situ gelling system using carbapol934 and
evaluated. The best in-situ gelling formulation (N4G5) was sufficiently
mucoadhesive, corneal toxicity, antibacterial activity and free from ocular
irritancy.
PMID- 27610145
TI - Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal
Candidiasis.
AB - The present investigation was designed to formulate a natural tablet for the
treatment of vaginal candidiasis in order to eliminate side effects that are
caused by existing antifungal drugs. Curcumin has promising antifungal activity
in comparison with the existing azole antifungal drugs. Bioadhesive curcumin
vaginal tablets were prepared by direct compression with different ratios of
biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were
characterized by studies of friability, hardness, hydration, DSC, mucoadhesion,
In-vitro release and antifungal activity. DSC and FT-IR data indicate there was
no interaction between the drug and the excipients and also polymer concentration
has some effects on melting point of curcumin. Formulation F3 showed the best
results in terms of swelling and mucoadhesion together with prolonged drug
release. The antifungal activity of the Curcumin tablet has demonstrated a
significant effect against Candida albicans. Hence, the study indicates the
possible and effective use of curcumin bioadhesive monolithic vaginal tablet for
vaginal candidiasis as a promising natural antifungal treatment.
PMID- 27610146
TI - Enhancement of Anti-Dermatitis Potential of Clobetasol Propionate by DHA
[Docosahexaenoic Acid] Rich Algal Oil Nanoemulsion Gel.
AB - The aim of the present study was to investigate the potential of nanoemulsion
formulation for topical delivery of Clobetasol propionate (CP) using algal oil
(containing omega-3 fatty acids) as the oil phase. CP has anti-inflammatory,
immunomodulatory and antiproliferative activities. However, its clinical use is
restricted to some extent due to its poor permeability across the skin. Algal oil
was used as the oil phase and was also exploited for its anti-inflammatory effect
along with CP in the treatment of inflammation associated with dermatitis.
Nanoemulsion formulations were prepared by aqueous phase titration method, using
algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co
surfactant and aqueous phase respectively. Furthermore, different formulations
were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory,
irritation and contact dermatitis studies. The optimized nanoemulsion was
converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971
and had a viscosity of 97.57 +/- 0.04 PaS. The optimized formulation had small
average diameter (120 nm) with zeta potential of -37.01 mV which indicated good
long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and
41.04% inhibition of inflammation for drug loaded and placebo formulations
respectively. The assessment of skin permeation was done by DSC and
histopathology studies which indicated changes in the structure of epidermal
membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in
the treatment with the CP-loaded nanoemulsion could be related to the higher anti
inflammatory effect in comparison with placebo nanoemulsion gel.
PMID- 27610147
TI - Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin
HCl Based on Effervescence and Swelling.
AB - An oral sustained-release floating tablet formulation of metformin HCl was
designed and developed. Effervescence and swelling properties were attributed on
the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination,
respectively. Tablet composition was optimized by response surface methodology
(RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken
design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A),
amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as
independent variables. Floating lag time in sec (Y1), cumulative percent drug
released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets
from the optimized formulation were also stored at accelerated stability
condition (40 degrees C and 75% RH) for 3 months to assess their stability
profile. RSM could efficiently optimize the tablet composition with excellent
prediction ability. In-vitro drug release until 12 h, floating lag time, and
duration of floating were dependent on the amount of three selected independent
variables. Optimized tablets remained floating for more than 24 h with a floating
lag time of less than 4 min. Based on best fitting method, optimized formulation
was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study
revealed that optimized formulation was stable for three months without any major
changes in assay, dissolution profile, floating lag time and other physical
properties.
PMID- 27610149
TI - Development of pH Sensitive Nanoparticles for Intestinal Drug Delivery Using
Chemically Modified Guar Gum Co-Polymer.
AB - The aim of the research work was to chemically modify guargum (GG) as a pH
sensitive co-polymer and formulating intestinal targeting ESO nanoparticles (NPs)
using the synthesized co-polymer. Poly acrylamide-grafted-guar gum (PAAm-g-GG) co
polymer was synthesized by free radical polymerization. Chemical modification of
PAAm-g-GG by alkaline hydrolysis results in formation of a pH-sensitive co
polymer. The effect of GG and acryl amide (AAm) on grafting was studied.
Esomeprazole magnesium (ESO) loaded pH sensitive NPs were prepared by nano
emulsification polymer crosslinking method and characterized. Sixteen
formulations were prepared and the concentration of process variables wasvaried
to obtain nanoparticles of 200-600 nm. The NPs were found to be homogenous in
size distribution. The encapsulation efficiency and drug loading ranged from
33.2% to 50.1% and 12.2% to 17.2% respectively. Particle size, encapsulation
efficiency and drug loading increasedalong with co-polymer concentration. In
vitro release studies at pH 1.2 for 2 h, followed by pH 6.8 showed that
environment pH significantly affected the drug release. SEM has shown that NPsare
spherical with smooth surface. The pH sensitive PAAm-g-GGNPs resisted the initial
release of the drug from the drug loaded NPs in acidic pH and delayed the release
process to a longer period in alkaline environment.
PMID- 27610148
TI - Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent.
AB - Atorvastatin calcium, the lipid lowering agent, is taken as a model drug
characterized by poor water solubility and bioavailability. In this study an
attempt was made for preparation of nanocrystals using high pressure
homogenization. A number of stabilizers were included as well as polymers at
different concentrations, and the formulations were homogenized for ten cycles at
a pressure of 1000 bars. The obtained nano crystals were evaluated by determining
their size, zeta potential, saturated solubility and dissolution rate. Results
revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate
ratio, possessed the highest saturated solubility and dissolution rate, and hence
was analyzed by X-ray diffraction analysis, differential scanning calorimetry,
Fourrier transform infrared spectroscopy and scanning electron microscopy. An in
vivo study was carried out on the successful formulation in comparison to drug
powder using rats as experimental animals. A significant increase in the area
under the concentration-time curve Cpmax and MRT for nanocrystals was observed in
comparison to the untreated atorvastatin calcium.
PMID- 27610150
TI - Formulation of a Traditionally Used Polyherbal Product for Burn Healing and HPTLC
Fingerprinting of Its Phenolic Contents.
AB - Nowadays, plants have been considered as powerful agents for treatment of
disorders regarding to their traditional use. In Iranian Traditional Medicine
(ITM), plants have a special role in the treatment of various diseases. Burns
with their devastating outcomes have been discussed in ITM as well. In the
present study, a polyherbal ointment (PHO), retrieved from ITM, was formulated
for burn healing and it's HPTLC fingerprint was prepared. Aqueous extracts of
Malva sylvestris and Solanum nigrum leaves and oily extract of Rosa damascena
petals (4.85%, 4.85% and 33%, respectively) were added to white beeswax, eucerin
and white petrolatum as ointment base. In addition to the microbiological tests,
physical stability and rheological behavior of the product were assessed.
Fingerprinting of phytochemical constituents of PHO was performed by using silica
gel plates and toluene: ethyl acetate: acetic acid (60:40:1) and ethyl acetate:
formic acid: acetic acid: water (100:11:11:10) as mobile phases. The results
showed that PHO was stable towards physical changes and successfully passed
microbiological tests. Moreover, PHO exhibited plastic behavior which is in favor
of a topical burn product. In addition, HPTLC fingerprinting of PHO demonstrated
the presence of several phenolic constituents corresponding to the plant
extracts. Regarding to the role of phenolic compounds in wound healing process,
PHO could be an appropriate candidate for burn healing with respect to its
traditional use in ITM. Moreover, HPTLC fingerprinting could be utilized as an
applicable method for quality control of the prepared formulation.
PMID- 27610152
TI - A stability-Indicating HPLC Method for Simultaneous Determination of Creatine
Phosphate Sodium and its Related Substances in Pharmaceutical Formulation.
AB - The objective of the study was to develop a simple, specific and stability
indicating HPLC method for the simultaneous determination of creatine phosphate
sodium (CPS) and its related substances in pharmaceutical formulation. Separation
of creatine phosphate sodium from its major process impurities and degradation
products was achieved on a Hypersil BDS C18 column (250 * 4.6 mm, 5 MUm) with an
aqueous mobile phase containing 0.2% (w/v) tetrabutylammonium hydroxide (TAH) and
0.2% (w/v) monopotassium phosphate adjusted to pH 6.6 with orthophosphoric acid
at a flow rate of 1.0 mL min(-1). The analytes were detected at 210 nm. Different
chromatographic parameters were carefully optimized. The relative response
factors for creatine, creatinine and creatinine phosphate disodium salt relative
to CPS were determined. The method has been validated with respect to solution
stability, system suitability, LOD, LOQ, linearity, accuracy, precision,
specificity and robustness. The validation criteria were met in all cases. The
developed method was successfully applied to determine the purity of CPS in
pharmaceutical formulation.
PMID- 27610151
TI - Voltammmetric Determination of Captopril Using Multiwall Carbon Nanotubes Paste
Electrode in the Presence of Isoproterenol as a Mediator.
AB - The electrocatalytic oxidation of captopril (CAP) was studied by modified carbon
nanotubes paste electrode in the presence of isoproterenol (ISPT) using cyclic
voltammetry (CV), chronoamperometry and square wave voltammetry (SWV). Also, the
values of catalytic rate constant (k), and electron transfer coefficient (alpha)
for CAP were calculated. The mechanism of CA electrochemical behavior at the
modified electrode surface was analyzed by various electrochemical methods in the
presence of mediator. The prepared modified electrode showed voltammetric
responses with high sensitivity for CAP, making it very suitable for the
detection of CAP at trace levels. Under the optimized conditions, the peak
current was linear to CAP concentration over the concentration range of 0.3 to 90
MUmol L(-1) using SWV. The detection limit was 0.1 MUmol L(-1). The proposed
method was successfully applied for the determination of CAP in the urine, tablet
and patient urine samples.
PMID- 27610154
TI - Simultaneous Determination of Diosmin and Hesperidin in Pharmaceuticals by RPLC
using Ionic Liquids as Mobile Phase Modifiers.
AB - Diosmin and hesperidin are natural flavonoid glycosides found in various plant
materials, mainly in citrus fruits in different concentrations. Diosmin for
pharmaceutical use is obtained mainly semi-synthetically from hesperidin.
Hesperidin often accompanies diosmin as a natural impurity in different
pharmaceutical formulations; therefore, a simple, fast and precise method for the
simultaneous assay of diosmin and hesperidin in pharmaceutical formulations has
been developed to control their contents. Chromatographic resolution was
performed using a column with C-18 packing and the following mobile phase:
methanol/water (45:55, v/v) with 0.025% added didecyldimethylammonium lactate,
which significantly affects retention, shortening analysis time and having a
positive impact on the symmetry of resulting chromatographic peaks. The method
shows linearity between 2.5 and 100 MUg/mL, high repeatability (0.39 and 0.42%
for diosmin and hesperidin, respectively) and accuracy of 96 to 102% for both the
assayed compounds. Intraday and interday precision of the new method were less
than RSD% 1, 2. The limit of detection of the assayed compounds is 2.5 and 1.2
MUg/mL for diosmin and hesperidin, respectively. The method was tested on several
pharmaceutical products available in Poland.
PMID- 27610153
TI - A Peroxidase-linked Spectrophotometric Assay for the Detection of Monoamine
Oxidase Inhibitors.
AB - To develop a new more accurate spectrophotometric method for detecting monoamine
oxidase inhibitors from plant extracts, a series of amine substrates were
selected and their ability to be oxidized by monoamine oxidase was evaluated by
the HPLC method and a new substrate was used to develop a peroxidase-linked
spectrophotometric assay. 4-(Trifluoromethyl) benzylamine (11) was proved to be
an excellent substrate for peroxidase-linked spectrophotometric assay. Therefore,
a new peroxidase-linked spectrophotometric assay was set up. The principle of the
method is that the MAO converts 11 into aldehyde, ammonia and hydrogen peroxide.
In the presence of peroxidase, the hydrogen peroxide will oxidize 4
aminoantipyrine into oxidised 4-aminoantipyrine which can condense with vanillic
acid to give a red quinoneimine dye. The production of the quinoneimine dye was
detected at 490 nm by a microplate reader. The ?OD value between the blank group
and blank negative control group in this new method is twice as much as that in
Holt's method, which enables the procedure to be more accurate and avoids the
produce of false positive results. The new method will be helpful for researchers
to screening monoamine oxidase inhibitors from deep-color plant extracts.
PMID- 27610155
TI - Validated Colorimetric Assay of Clonidine Hydrochloride from Pharmaceutical
Preparations.
AB - Clonidine hydrochloride is an antihypertensive agent used for migraine
prophylaxis, attention deficit hyperactivity disorder, menopausal flushing and
Tourette syndrome. The quantity of the active substance in pharmaceutical
preparations must be within specific limits, in agreement with the respective
label claim. Therefore, the aim of this study was to establish the conditions for
two spectrophotometric methods for clonidine determination, based on the
formation of the ion pair complex between clonidine hydrochloride and thymol
blue/bromophenol blue. A Jasco UV-Vis 530 spectrophotometer was used for the
analysis and the maxim absorbance was measured at 418 nm/448 nm against blank
solution. After validation, the methods were used for quantification of clonidine
hydrochloride in two commercial samples (tablets). The recovery of active
substance varies between 98.06 and 100.13 % without interferences from the
excipients.
PMID- 27610156
TI - Validation of an Analytical Method for Determination of 13 priority polycyclic
aromatic hydrocarbons in mineral water using dispersive liquid-liquid
microextraction and GC-MS.
AB - Dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography
mass spectrometry (GC-MS) was used for the extraction and determination of 13
polycyclic aromatic hydrocarbons (PAHs) in mineral water samples. In this
procedure, the suitable combination of extraction solvent (500 uL chloroform) and
disperser solvent (1000 uL acetone) were quickly injected into the water sample
(10.00 mL) by Hamilton syringe. After centrifugation, 500 uL of the lower organic
phase was dried under a gentle stream of nitrogen, re-dissolved in chloroform and
injected into GC-MS. Chloroform and acetone were found to be the best extraction
and disperser solvent, respectively. Validation of the method was performed using
spiked calibration curves. The enrichment factor ranged from 93 to 129 and the
recovery ranged from 71 to 90%. The linear ranges for all the PAHs were 0.10-2.80
ngmL(-1). The relative standard deviations (RSDs) of PAHs in water by using
anthracene-d10 as internal standard, were in the range of 4-11% for most of the
analytes (n = 3). Limit of detection (LOD) for different PAHs were between 0.03
and 0.1 ngmL(-1). The method was successfully applied for the analysis of PAHs in
mineral water samples collected from Tehran.
PMID- 27610157
TI - Design, Synthesis and Biological Evaluation of4-(Imidazolylmethyl)-2-(4
methylsulfonyl phenyl)-Quinoline Derivatives as Selective COX-2 Inhibitors and In
vitro Anti-breast Cancer Agents.
AB - A new group of 4-(Imidazolylmethyl)quinoline derivatives possessing a
methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring
were designed and synthesized as selective COX-2 inhibitors and in-vitroanti
breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all
the compounds were potent and selective inhibitors of the COX-2 isozyme with IC50
values in the potent range 0.063-0.090 uM, and COX-2 selectivity indexes in the
179.9 to 547.6 range. Molecular modeling studies indicated that the
methylsulfonyl substituent can be inserted into the secondary pocket of COX-2
active site for interactions with Arg(513). Cytotoxicity of quinolines 9a-e
against human breast cancer MCF-7 and T47D cell lines were also evaluated. All
the compounds 9a-e were more cytotoxic against MCF-7 cells in comparison with
those of T47D which express aromatase mRNA less than MCF-7 cells.The data showed
that the increase of lipophilic properties of substituents on the C-7 and C-8
quinoline ring increased their cytotoxicity on MCF-7cells andCOX-2 inhibitory
activity. Among the quinolines 9a-e, 4-((1H-Imidazol-1-yl)methyl) 7,8,9,10
tetrahydro-2-(4-methylsulfonylphenyl)-benzo[h]quinoline (9d)was identified as the
most potent andselective COX-2inhibitor as well as the most cytotoxic agent
against MCF-7 cells.
PMID- 27610158
TI - Synthesis, Biological Evaluation and Docking Analysis of Some Novel Quinazolin
Derivatives as Antitumor Agents.
AB - Different acid chlorides (2a-d) reacted with anthranilic acid to produce 2
substituted-3, 1-benzoxazin-4-one (3a-d) which was used as starting material to
synthesize some condensed and non-condensed heterocyclic compounds by reaction
with nitrogen nucleophiles e.g., hydrazine hydrate, and formamide. Some of the
newly synthesized analogues were chosen to evaluate their cytotoxic activity
against human carcinoma cell lines (HePG2- MCF7- A549). The docking and the
cytotoxic activity results revealed that nearly all of the compounds containing N
phenyl aniline showed significant inhibition for the three cell lines.
PMID- 27610159
TI - Potent Anti-Inflammatory Activity of Tetramethylpyrazine Is Mediated through
Suppression of NF-k.
AB - The purpose of the current study was to evaluate the anti-inflammatory activity
of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells
(SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear
cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The
colitis cells treated by oxazolone were randomly divided into model, low dose,
middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L
tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the
oxazolone-induced group was lower than that in the normal group. Compared with
model group, apoptotic rate of SMC was significantly increased in the high dose
group, while the apoptotic rate of LPMC in the middle dose group was increased.
Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear
factor kappa B (NF-kB), transcription factor-activated protein-1 (AP-1) and
nuclear factor of activated T cells (NF-AT) were higher in model group.
Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced
by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA
level of AP-1 among the three different doses of tetramethylpyrazine treated
groups. However, no significant difference was observed in the mRNA levels of NF
AT and NF-kappaB between normal and middle groups. Tetramethylpyrazine promoted
the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of
transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced
colitis mice. The study provides a novel insight into the mechanism behind the
effect of etramethylpyrazine on colitis.
PMID- 27610160
TI - Ocular Dorzolamide Nanoliposomes for Prolonged IOP Reduction: in-vitroand in-vivo
Evaluation in Rabbits.
AB - Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it
has a short residence time in the eye. The aim of this study is to develop ocular
dorzolamide HCl nanoliposomes (DRZ - nanoliposomes) and to evaluate their
potential use for the treatment of ocular hypertension. Nanoliposomes were
prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration
(TLH) method with 7:3 and 7:4 molar ratios of phosphatidylcholine:cholesterol.
The physicochemical properties of the formulations were investigated.
Formulations with 7:4 lipid ratios were evaluated in terms of drug release,
physical stability and ex-vivo permeation through the excised albino rabbit
cornea. The rabbits in groups of 6 were treated with selected DRZ - nanoliposomes
or dorzolamide solution or marketed dorzolamid preparation (Biosopt(r)) and
intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio
entrapped greater amount of drug compared to those with 7:3 lipid components
ratio. DRZ - nanoliposomes with 7:4 lipid ratio showed more transcorneal
permeation than Dorzolamide solution (p<0.05); and the formulation prepared by
TLH method exhibited higher permeability than that prepared by REV method
(p<0.05). The selected DRZ - nanoliposomes showed greater IOP lowering activity
and a more prolonged effect compared to dorzolamide solution and Biosopt(r). DRZ
nanoliposomes prepared by TLH method with 7:4 ratios showed promising results as
a candidate for the treatment of ocular hypertension.
PMID- 27610161
TI - FTIR Biospectroscopy Investigation on Cisplatin Cytotoxicity in Three Pairs of
Sensitive and Resistant Cell Line.
AB - Fourier Transformed Infrared Spectroscopy (FTIR) has extensively been used for
biological applications. Cisplatin is one the most useful antineoplastic
chemotherapy drugs for a variety of different human cancers. One of the clinical
problems in its application, which would consequently affect the therapeutic
outcome of its application, is the occurrence of resistance to this agent. In
this project three different pairs of sensitive and resistant cell lines of human
ovarian A2780 and its resistant pair of A2780-CP, human ovarian OV2008 and its
resistant pair of C13, and finally human lung carcinoma of HTB56 and its
resistant pair of HTB56-CP were grown in the laboratory under the standard
procedure. Saline was exposed to control cells, whereas 1, 5 and 10 ug/mL of
cisplatin was exposed to experimental cells, for 1 h. Cells were then collected
and lyophilized from which spectra were taken. According to our results, we could
not trigger a well-recognized cells biomolecular band at 1015 cm(-1), being
modified after exposure to cisplatin in all cell lines. On the other hand, there
was a clear dose-dependent increase in protein beta-sheet structure related peaks
shift in resistant cell lines after exposure to cisplatin. This would probably
indicate an easier protein interaction site for cisplatin in the resistant cell
lines, which would probably inhibit cisplatin from binding to DNA, as the
cytotoxic target. As a conclusion, FTIR biospectroscopy has proven its potency to
identify the interactions, as well as the false engagement cellular sites for
cisplatin in sensitive and resistant cell lines.
PMID- 27610162
TI - Impact of Pharmaceutical Impurities in Ecstasy Tablets: Gas Chromatography-Mass
Spectrometry Study.
AB - In this study, a simple and reliable method by gas chromatograph-mass
spectrometry (GC-MS) was developed for the fast and regular identification of 3,
4-MDMA impurities in ecstasy tablets. In so doing, 8 samples of impurities were
extracted by diethyl ether under alkaline condition and then analyzed by GC-MS.
The results revealed high MDMA levels ranging from 37.6% to 57.7%. The GC-MS
method showed that unambiguous identification can be achieved for MDMA from 3, 4
methylenedioxyamphetamine (MDA), Amphetamine (AM), methamphetamine (MA) and
ketamine (Keta) compounds, respectively. The experimental results indicated the
acceptable time window without interfering peaks. It is found that GC-MS was
provided a suitable and rapid identification approach for MDMA (Ecstacy) tablets,
particularly in the Forensic labs. Consequently, the intense MDMA levels would
support the police to develop a simple quantification of impurity in Ecstasy
tablets.
PMID- 27610163
TI - Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA
MB231 as a Breast Cancer Cell Line.
AB - Cancer is one of the main causes of mortality in the world which appears by the
effect of enviromental physico-chemical mutagen and carcinogen agents. The
identification of new cytotoxic drug with low sid effects on immune system has
developed as important area in new studies of immunopharmacology. Curcumin is a
natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer
properties. Its therapeutic potential is substantially hindered by the rather low
water solubility and bioavailability, hence the need for suitable carriers. In
this report we employed nanogel-based nanoparticle approach to improve upon its
effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the
technique of self-assembly. Curcumin was loaded into the nanogels. The surface
morphology of the prepared nanoparticles was determined using SEM and TEM. The
other objective of this study was to examine the in vitro cytotoxic activity of
cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line
(MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were
assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
and dye exclusion assay. Transmission electron microscopy confirmed the particle
diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was
significantly inhibited by curcumin and nanocurcumin in a concentration-dependent
manner in defined times. There were significant differences in IC50 curcumin and
nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ
solution. The high drug-targeting potential and efficiency demonstrates the
significant role of the anticancer properties of curcumin -loaded nanoparticles.
PMID- 27610164
TI - Effect-Directed Analysis for the Antioxidant Compound in Salvia verticillata.
AB - Salvia genus is one of the largest genera of the Lamiaceae family. Its species
have been used for a wide variety of disorders in the local traditional medicine
systems. Therefore, the genus has been the subject of several phytochemical and
biological studies. The aim of the study was to identify the major antioxidant
compound(s) from the methanol extract of Salvia verticillata using activity
guided fractionation. The crude extract showed strong antioxidant activities in
DPPH and beta-carotene/linoleic acid tests. The ethyl acetate fraction also
exhibited a potent free radical scavenging activity compared to the other
fractions. Further fractionation and purification of the ethyl acetate fraction
using chromatography methods yielded a compound with high antioxidant capacity.
The isolated active compound was determined as chrysoeriol. It showed a dose
dependent free radical scavenging activity with an IC50 (DPPH scavenging) value
of 93.32 (80.23 - 108.57) mM.
PMID- 27610165
TI - Evaluation of Hepatoprotective Effect of Silymarin Among Under Treatment
Tuberculosis Patients: A Randomized Clinical Trial.
AB - Hepatic toxicity is the most serious adverse effect of anti-tuberculosis drugs.
This study was performed to evaluate the efficacy of silymarin as a
hepatoprotective herbal agent. In a randomized double blind clinical trial, 70
new cases of pulmonary tuberculosis were divided into two groups. The
intervention group was assigned to receive silymarin and the control group
received placebo. Tuberculosis was treated by classic regimen consisting
isoniazid, rifampin, pyrazinamide and ethambutol. No statistically significant
difference was found between the two groups concerning the frequency of drug
induced liver injury or mild elevation of liver enzymes. Silymarin was safe
without any major side effect. Our results showed no significant hepatoprotective
effect of silymarin among patients on tuberculosis treatment.
PMID- 27610166
TI - Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent
Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction
Injury.
AB - This study was designed to investigate the therapeutic effects of saffron (Crocus
sativus L.) and its main constituent crocin on neuropathic pain behavioral
responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar
rats (200 to 250 g) were randomly assigned into 5 groups: Sham + saline, CCI +
saline, CCI+ saffron (30 mg/kg), CCI + crocin (15 mg/kg) and CCI + crocin (30
mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve.
Two weeks after nerve lesion, injections of saline, saffron or crocin were
started and continued until 26(th) day post-surgery. Pain behavioral responses
including mechanical allodynia (von Frey filament testing) and thermal
hyperalgesia were measured in 14, 17, 20, 23, 26, and 40(th) days after CCI. CCI
significantly increased pain behavioral responses. Saffron and crocin (30 mg/kg)
decreased thermal hyperalgesia and mechanical allodynia on day 26, and this
effect continued until the day 40. Crocin at lower dose (15 mg/kg) was
ineffective. These findings indicate that treatment of saffron and crocin after
CCI may have a therapeutic effect against neuropathic pain, suggesting that these
substances may offer new strategies for the treatment of this highly debilitating
condition.
PMID- 27610167
TI - Dynamic Variation Patterns of Aconitum Alkaloids in Daughter Root of Aconitum
Carmichaelii (Fuzi) in the Decoction Process Based on the Content Changes of Nine
Aconitum Alkaloids by HPLC- MS- MS.
AB - The chemical components in the decoctions of Chinese herbal medicines are not
always the same as those in the crude herbs because of the insolubility or
instability of some compounds. In this work, a high-performance liquid
chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass
spectrometry method was developed to explore dynamic variation patterns of
aconitum alkaloids in Fuzi during the process of decocting aconite root. The
fragmentation patterns of aconitum alkaloids using ESI and collision-induced
dissociation (CID) techniques were reported. This assay method was validated with
respect to linearity (r(2) > 0.9950), precision, repeatability, and accuracy
(recovery rate between 94.6 and 107.9%).The result showed that the amounts of
aconitum alkaloids in the decoction at different boiling time varied
significantly. In the decoction process,the diester- type alkaloids in crude
aconite roots have transformed into Benzoylaconines or aconines.
PMID- 27610168
TI - Peganum Harmala L. Extract Reduces Oxidative Stress and Improves Symptoms in 6
Hydroxydopamine-Induced Parkinson's Disease in Rats.
AB - Parkinson's disease is one of the most common neurodegenerative disorders. There
are many documents about the effects of oxidative stress in Parkinson's disease
etiology. Angiotensin II activates NADPH dependent oxidases and causes
superoxides formation. Peganum harmala L. extract, which has angiotensin
converting enzyme (ACE) inhibitory effect, is considered to evaluate oxidative
stress inhibition and Parkinson's disease improvement. Male rats weighting 200
250 g were divided into 5 groups: Control, Neurotoxin (injection of 6
hydroxydopamine into left hemisphere substantia nigra), Peganum harmala's seeds
aqueous extract (10 mg/kg) and captopril (5 mg/kg). Peganum harmala and captopril
were injected intraperitonealy -144, -120, -96, -72, -48, -24, -2, 4 and 24 h
relative to 6-hydroxydopamine injection time. Muscle stiffness, apomorphine
induced unilateral rotation, amount of brain's protein oxidation and lipid
peroxidation, ACE activity and histology of substantia nigra were assayed in all
groups. Peganum harmala improved Muscle stiffness and one-direction rotation
behavior significantly. It also reduced brain's lipid and protein oxidation
levels in neurotoxin-injected rats significantly. In Peganum harmala group
compared to control group, brain's ACE activity was significantly inhibited. In
histological study, Peganum harmala prevented degeneration of dopaminergic
neurons, too. In conclusion, aqueous extract of Peganum harmala could prevent
symptoms and reduced oxidative stress markers in rats with Parkinson's disease
induced by 6-hydroxydopamine.
PMID- 27610169
TI - In-vitro Evaluation of Protective Effects on DNA Damage and Antioxidative
Activities of Ilex Spinigera Loes. Extracts.
AB - Ilex spinigera (Aquifoliaceae) plant is an evergreen tree or shrub with thick
glossy dark green leaves and red fruits. This plant has medicinal properties and
has been used traditionally in northern Iran for malaria treatment. The aim of
this work is to evaluate the antioxidative activities and the inhibitory effect
of I. spinigera on the oxidation of DNA. We have found no reports about the
popular use of I. spinigera in terms of its chemistry and biology. In this study
we report the antioxidant activity of I. spinigera extracts for the first time.
Water, ethanol and methanol were used as extraction solvents. Various
experimental models including iron (III) reducing power, total antioxidant
capacity, DPPH radical scavenging activity, PAB assay and in-vitro inhibition of
AAPH-induced oxidation of DNA were used for characterization of antioxidant
activity of the extracts. The three extracts showed varying degrees of efficacy
in each assay in a dose-dependent manner. The aqueous extract with the highest
content of total phenolics, was the most potent antioxidant in all assays except
in DPPH assay. The methanol extract with the highest amount of total flavonoids
was the potent scavenger of DPPH radical with an IC50 value of 102.22 +/- 0.001
MUg/mL. Aqueous extract of I. spinigera also showed the protective effect on DNA
damage-induced by AAPH. According to our results, I. spinigera leaves extract
have the potential for chemoprotective studies.
PMID- 27610170
TI - Study of Sedative-Hypnotic Effects of Aloe vera L. Aqueous Extract through
Behavioral Evaluations and EEG Recording in Rats.
AB - In this study, we investigated the sedative and hypnotic effects of the aqueous
extract of Aloe vera on rats. In order to evaluate the overall hypnotic effects
of the Aloe vera extract, open field and loss of righting reflex tests were
primarily used. The sedative and hypnotic effects of the extract were then
confirmed by detection of remarkable raise in the total sleeping time through
analysis of electroencephalographic (EEG) recordings of animals. Analysis of the
EEG recordings showed that there is concomitant change in Rapid Eye Movement
(REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged
total sleeping time. Results of the current research show that the extract has
sedative-hypnotic effects on both functional and electrical activities of the
brain.
PMID- 27610171
TI - Influence of Total Anthocyanins from Bitter Melon (Momordica charantia Linn.) as
Antidiabetic and Radical Scavenging Agents.
AB - The majority of the antioxidant and antidiabetic activities of fruits are
anthocyanins; a group of polyphenolics that are responsible for the color of many
fruits, vegetables and flowers. The harvesting time, storage conditions,
maturity, extraction steps etc. are very important for the biological activities
based on the alteration of chemical composition. The free radical scavenging and
antidiabetic activities of total anthocyanins from bitter melon (Momordica
charantia Linn) fruit (TAMC) were evaluated by considering four harvesting times.
The free radical scavenging activities of the TAMC samples were assessed using
DPPH(*), DMPD(*+) and ABTS(*+) assays against BHA, rutin and trolox standards.
September as a harvesting period (TAMC-S) had effective DPPH(*) (SC50 2.55 +/-
0.08 MUg/mL), DMPD(*+) (SC50 2.68 +/- 0.09 MUg/mL) and ABTS(*+) (SC50 8.19 +/-
0.09 MUg/mL) scavenging activities compared with other samples and standards. In
addition, August (TAMC-A) as a harvesting period showed very influential
inhibitory activity against alpha-amylase (IC50 56.86 +/- 1.12 MUg/mL) and
moderate inhibitory activity against alpha-glucosidase (IC50 88.19 +/- 0.74
MUg/mL). In comparison, pharmaceutical active ingredients such as acarbose
exhibited anti-amylase and anti-glucosidase activities with IC50 values of 93.07
+/- 1.49 MUg/mL and 77.25 +/- 1.20 MUg/mL respectively. These results suggest
that the correct selection of harvest period can significantly increase
anthocyanin quantity because of the pharmaceutic properties of TAMC.
Consequently, TAMC may be interesting for incorporation in pharmaceutical
preparations for human health, since it can suppress hyperglycaemia that can be
also used as food additives due to its antiradical activity.
PMID- 27610172
TI - Primula auriculata Extracts Exert Cytotoxic and Apoptotic Effects against HT-29
Human Colon Adenocarcinoma Cells.
AB - Primula auriculata (Tootia) is one of the most important local medicinal plants
in Hamedan district, Iran. To investigate cytotoxicity and apoptosis induction of
crude methanolic extract and different fraction of it, we compared several
methods on HT-29 human colon Adenocarcinoma cells. Cancer cell proliferation was
measured by 3-(4, 5-dimethylthiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT)
assay and apoptosis induction was analyzed by fluorescence microscopy (acridin
orange/ethidium bromide, annexin V/propidium iodide staining, TUNEL assay and
Caspase-3 activity assay). Crude methanolic extract (CM) inhibited the growth of
malignant cells in a dose-dependent manner. Among solvent fractions, the
dichloromethane fraction (CF) was found to be the most toxic compared to other
fractions. With double staining methods, high percentage of 40 ug/mL of (CM) and
(CF) treated cells exhibited typical characteristics of apoptotic cells.
Apoptosis induction was also revealed by apoptotic fragmentation of nuclear DNA
and activation of caspas-3 in treated cells. These findings indicate that crude
methanolic extract and dichloromethan fraction of P.auriculata induced apoptosis
and inhibited proliferation in colon cancer cells and could be used as a source
for new lead structures in drug design to combat colon cancer.
PMID- 27610173
TI - Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic
Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.
AB - Recently, extensive efforts have been made to understand the rate of energy
expenditure and the weight gain associated with atypical antipsychotic treatment,
including identification of markers of obesity risk. In recent years, leptin, an
adipocyte hormone, has gained significant interest in psychiatric disorders.
S100B has been considered as a surrogate marker for astrocyte-specific damage in
neurologic disorders. Also, S100B has been detected in adipose with concentration
as high as nervous tissue as a second release source. In this study we evaluated
the relationship between S100B and leptin in schizophrenic patients under
treatment with clozapine and risperidone.This study included 19 patients meeting
the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25
kg/m(2) and suffering schizophrenia for more than 3 years and from this study.
Twenty five healthy controls were group matched for age and gender whose BMI was
16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom
scale (PANSS) were assessed at admission and after six weeks. During the study,
S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01).
Also, there were negative correlation between serum S100B level and PANSS
negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive
correlation between leptin level and PANSS suggested a potential role for leptin
which can mediate the link between antipsychotic induced weight gain and
therapeutic response in schizophrenia.
PMID- 27610174
TI - A 16 Month Survey of Cyclosporine Utilization Evaluation in Allogeneic
Hematopoietic Stem Cell Transplant Recipients.
AB - OBJECTIVES: Graft versus host disease (GVHD) is a life threatening reaction in
the stem cell transplantation process. Nowadays Cyclosporine is the most commonly
utilized agent for GVHD prophylaxis and it has a major role in successful
transplantation. Cyclosporine has been applied for many years in this field but
it could be stated that currently no general consensus is available for its
optimal method of administration. Conditions related to cyclosporine
administration and possible related adverse reactions observed closely in our
patients with the aim of constructing a comprehensive practice guideline in the
future. PATIENTS AND METHODS: Allogeneic stem cell transplant recipients who have
been taking cyclosporine were monitored during and after their hospitalization
while recording all observations on predefined questionnaires on the basis of
periodic clinical and laboratory examinations for a 16 month period. RESULTS:
Mean recorded duration of infusions was 1.44 +/- 0.68 h and by twice daily
administration, means intravenous and oral dose was 101.85 +/- 22.03 mg and
219.28 +/- 63.9 mg, respectively. A mean CsA trough level after about 12 h of
specified unique doses was 223 +/- 65 ng/mL. We found hypertension,
nephrotoxicity, neurotoxicity, hypertension, and dyslipidemia in about 14, 20,
48, and 94 percent of patients. CONCLUSIONS: This study proposed that permanent
guidance of healthcare team according to a fixed and standard method of
cyclosporine administration routine with using efficient facilities and protocols
would be helpful considerably for an optimal pharmacotherapy.
PMID- 27610175
TI - A Prospective Study to Assess Vancomycin Serum Concentrations inPediatric
Patients with Current Dosing Guidelines.
AB - Concerns about increasing bacterial resistance to vancomycin, have caused the
adult treatment guidelines to recommend higher trough concentrations based on the
type and location of infectious disease. Although these recommendations are not
specific to children, the values can be extrapolated. This prospective study was
designed to evaluate efficacy of current vancomycin dosing recommendations to
achieve therapeutic trough serum concentration in pediatric patients. Laboratory
data, vancomycin dosing and subsequent serum concentrations of children in a
community teaching pediatrics hospital were collected and analyzed. Trough serum
levels were determined at steady state and compared with Infectious Disease
Society of America (IDSA) 2011 guidelines for the treatment of Methicillin
Resistant Staphylococcus Aureus (MRSA) infections. In a prospective
observational, cross-sectional study in a university medical center in Tehran,
Iran, 50 patients, who received vancomycin for more than 4 doses, were recruited
and their trough vancomycin level was determined. The mean age and creatinine
clearance of patients were 5.47 +/- 4.24 and 87.5 +/- 31.25, respectively. Eleven
(22%) patients received vancomycin at 40 mg/kg/day (low dose) and 39 (78%) at 60
mg/kg/day (high dose). Considering trough goals of 10-14 and 15-20 mg/L in low
and high dose groups, serum levels in 91% (73% sub- therapeutics) and 85% (69%
sub-therapeutics) of patients were not in recommended therapeutic range,
respectively. This study has shown that current recommended vancomycin dosing
regimens in pediatric patients (40-60 mg/kg/day), resulted in sub-therapeutic
serum concentrations in our study population.
PMID- 27610176
TI - Clinical, Paraclinical, and Antimicrobial Resistance Features of Community
Acquired Acute Bacterial Meningitis at a Large Infectious Diseases Ward in
Tehran, Iran.
AB - In this study demographic, clinical, paraclinical, microbiological, and
therapeutic features of patients with community-acquired acute bacterial
meningitis admitted to a referral center for infectious diseases in Iran, have
been evaluated. Medical records of adult (> 18 years) individuals with confirmed
diagnosis of community-acquired bacterial meningitis during a 4-year period were
retrospectively reviewed. All required data were obtained from patients' medical
charts. Available findings about antimicrobial susceptibility of isolated
bacteria from CSF and/or blood were also collected. Kirby-Bauer disc diffusion
method was used to determine their antimicrobial susceptibility profile. Details
of medical management including antibiotic regimen, duration, patients' outcome,
and possible sequelae of meningitis were recorded. The most commonly isolated
microorganism from CSF or blood of patients was Streptococcus pneumonia (33.33%)
followed by Neisseria meningitidis (27.78%) and Haemophilus influenza (16.67%).
The most common antimicrobial regimen was ceftriaxone plus vancomycin (69.44%)
followed by ceftriaxone plus vancomycin plus ampicillin (11.11%). Neurological
sequelae of meningitis including cranial nerve palsy, deafness, and hemiparesis
were identified in 4 (11.11%), 2 (5.56%), and 1 (2.78%) subjects, respectively.
Regarding mortality, only 3 (8.33%) patients died from bacterial meningitis and
the remaining 33 individuals discharged from the hospital. In conclusion,
findings of the current study demonstrated that the mean incidence of acute
bacterial meningitis in a referral infectious diseases ward in Iran was 9
episodes per year. The majority cases of community-acquired acute bacterial
meningitis admitted to our center had negative CSF culture and classic triad of
meningitis was absent in them.
PMID- 27610177
TI - Knowledge discovery from patients' behavior via clustering-classification
algorithms based on weighted eRFM and CLV model: An empirical study in public
health care services.
AB - The rapid growing of information technology (IT) motivates and makes competitive
advantages in health care industry. Nowadays, many hospitals try to build a
successful customer relationship management (CRM) to recognize target and
potential patients, increase patient loyalty and satisfaction and finally
maximize their profitability. Many hospitals have large data warehouses
containing customer demographic and transactions information. Data mining
techniques can be used to analyze this data and discover hidden knowledge of
customers. This research develops an extended RFM model, namely RFML (added
parameter: Length) based on health care services for a public sector hospital in
Iran with the idea that there is contrast between patient and customer loyalty,
to estimate customer life time value (CLV) for each patient. We used Two-step and
K-means algorithms as clustering methods and Decision tree (CHAID) as
classification technique to segment the patients to find out target, potential
and loyal customers in order to implement strengthen CRM. Two approaches are used
for classification: first, the result of clustering is considered as Decision
attribute in classification process and second, the result of segmentation based
on CLV value of patients (estimated by RFML) is considered as Decision attribute.
Finally the results of CHAID algorithm show the significant hidden rules and
identify existing patterns of hospital consumers.
PMID- 27610178
TI - Administrative Process and Criteria Ranking for Drug Entering Health Insurance
List in Iran-TOPSIS-Based Consensus Model.
AB - The purposes of our study were to identify a drug entry process, collect, and
prioritize criteria for selecting drugs for the list of basic health insurance
commitments to prepare an "evidence based reimbursement eligibility plan" in
Iran. The 128 noticeable criteria were found when studying the health insurance
systems of developed countries. Four parts (involving criteria) formed the first
questionnaire: evaluation of evidences quality, clinical evaluation, economic
evaluation, and managerial appraisal. The 85 experts (purposed sampling) were
asked to mark the importance of each criterion from 1 to 100 as 1 representing
the least and 100 the most important criterion and 45 out of them replied
completely. Then, in the next questionnaire, we evaluated the 48 remainder
criteria by the same45 participants under four sub-criteria (Cost calculation
simplicity, Interpretability, Precision, and Updating capability of a criterion).
After collecting the replies, the remainder criteria were ranked by TOPSIS
method. Softwares "SPSS" 17 and Excel 2007 were used. The ranks of the five most
important criteria which were found for drug approval based on TOPSIS are as
follows: 1-domestic production (0.556), 2-duration of using (0.399), 3
independence of the assessment group (0.363) 4-impact budgeting (0.362) 5
decisions of other countries about the same drug (0.358). The numbers in
parenthesis are relative closeness alternatives in relation to the ideal
solution. This model gave a scientific model for judging fairly on the acceptance
of novelty medicines.
PMID- 27610179
TI - The use of complementary and alternative medicine in children with common
neurologic diseases.
AB - Complementary and alternative medicine (CAM) is a phrase used to describe
additional health care methods such as mind/body practices and natural products
not regarded as treatments by conventional medicine. The use of CAM in children
with common neurologic diseases is more frequent than its use in healthy children
(24%-78% vs. 12%). However, less than half of patients report such use to their
physicians. The preferred modalities of CAM vary in different countries due to
their different cultures and traditions. The most common factor significantly
associated with the use of CAM is parental CAM use in most studies. The frequency
of the use of CAM in children and adults with neurologic diseases is similar, and
both rates are higher than the rates in those without these conditions. The
preferred modalities of CAM in adults are diverse, and megavitamins and mind/body
therapy (prayer and chiropractic care) are included. The most common factor
significantly associated with the use of CAM in adults with neurologic diseases
is high educational level. Physicians need to be concerned with patients' use of
CAM and provide correct information about CAM so that patients may make the right
decisions. Further study is needed to determine the evidence-based efficacy of
CAM use in children with common neurologic diseases.
PMID- 27610180
TI - Impact of perinatal environmental tobacco smoke on the development of childhood
allergic diseases.
AB - Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food
allergy, are most common chronic, noncommunicable diseases in childhood. In the
past few decades, the prevalence has increased abruptly worldwide. There are 2
possible explanations for the rising prevalence of allergic diseases worldwide,
that an increased disease-awareness of physician, patient, or caregivers, and an
abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms
remain largely unknown. Despite the continuing efforts worldwide, the etiologies
and rising prevalence remain unclear. Thus, it is important to identify and
control risk factors in the susceptible individual for the best prevention and
management. Genetic susceptibility or environments may be a potential background
for the development of allergic disease, however they alone cannot explain the
rising prevalence worldwide. There is growing evidence that epigenetic change
depends on the gene, environment, and their interactions, may induce a long
lasting altered gene expression and the consequent development of allergic
diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure
during critical period (i.e., during pregnancy and early life) are considered as
a potential cause of the development of childhood allergic diseases. However, the
causal relationship is still unclear. This review aimed to highlight the impact
of ETS exposure during the perinatal period on the development of childhood
allergic diseases and to propose a future research direction.
PMID- 27610181
TI - Clinical outcome of patients with refractory Kawasaki disease based on treatment
modalities.
AB - PURPOSE: Although a significant number of reports on new therapeutic options for
refractory Kawasaki disease (KD) such as steroid, infliximab, or repeated
intravenous immunoglobulin (IVIG) are available, their effectiveness in reducing
the prevalence of coronary artery lesions (CAL) remains controversial. This study
aimed to define the clinical characteristics of patients with refractory KD and
to assess the effects of adjuvant therapy on patient outcomes. METHODS: We
performed a retrospective study of 38 refractory KD patients from January 2012 to
March 2015. We divided these patients into 2 groups: group 1 received more than 3
IVIG administration+ steroid therapy, (n=7, 18.4%), and group 2 patients were
unresponsive to initial IVIG and required steroid therapy or second IVIG (n=31,
81.6%). We compared the clinical manifestations, laboratory results, and
echocardiographic findings between the groups and examined the clinical utility
of additional therapies in both groups. RESULTS: A significant difference was
found in the total duration of fever between the groups (13.0+/-4.04 days in
group 1 vs. 8.87+/-2.30 days in group 2; P=0.035). At the end of the follow-up,
all cases in group 1 showed suppressed CAL. In group 2, coronary artery aneurysm
occurred in 2 patients (6.4 %). All the patients treated with intravenous
corticosteroids without additional IVIG developed CALs including coronary artery
aneurysms. CONCLUSION: No statistical difference was found in the development of
CAL between the groups. Prospective, randomized, clinical studies are needed to
elucidate the effects of adjunctive therapy in refractory KD patients.
PMID- 27610183
TI - Venous angioma may be associated with epilepsy in children.
AB - PURPOSE: Venous angioma (VA) is the most common congenital abnormality of the
intracranial vasculature. This study aimed to investigate the relationship
between VA and epilepsy and to identify the characteristics of children with VA
and epilepsy. METHODS: The records of all patients aged less than 18 years who
underwent brain magnetic resonance imaging (MRI) at Pusan National University
Hospital were retrospectively reviewed. Patients with isolated VA and patients
with normal MRI were compared in terms of the prevalence of epilepsy. RESULTS: In
total, 2,385 pediatric patients who underwent brain MRI were enrolled. Isolated
VA was identified in 26 patients (VA group). Among the patients with normal MRI
findings, 225 age- and sex-matched patients to the VA-group were assigned to the
control group. Nine patients in the VA group (9 of 26, 34.6%) and 27 patients in
the control group (26 of 225, 11.5%; P<0.001) had epilepsy. In the VA group, 20
patients (76.9%) had the VA in the cerebral hemispheres, and 6 patients (23.1%)
had the VA in the brainstem and cerebellum. The latter showed a higher prevalence
of epilepsy (5 of 6, 83.3%) than the former (4 of 20, 20.0%; P=0.004). Among the
nine patients who had epilepsy with VA, patients whose VA involved the brainstem
and cerebellum showed a significantly higher frequency of abnormal
Electroencephalographic findings than patients whose VA involved the cerebral
hemispheres (P=0.016). CONCLUSION: VA, especially in the brainstem and
cerebellum, might be associated with epilepsy.
PMID- 27610182
TI - Clinical course and prognostic factors of childhood immune thrombocytopenia:
single center experience of 10 years.
AB - PURPOSE: This study aimed to evaluate the clinical course of childhood immune
thrombocytopenia (ITP) and to assess the risk factors for developing chronic ITP.
METHODS: The records of 64 children diagnosed with ITP from November 2005 and
December 2014 at single center were retrospectively analyzed. RESULTS: The median
age at diagnosis and the median platelet count were 1 year (range, 1 month to 15
years) and 9*10(9)/L (range, 0-84*10(9)/L), respectively. No patient experienced
severe bleeding. Nineteen children (29.7%) spontaneously recovered their platelet
count to >=100*10(9)/L at a median of 10 days. In total 45 patients (70.3%)
received intravenous immunoglobulin (IVIG) as first-line therapy, and showed
platelet recovery at 1 week. The final diagnosis of 55 (85.9%) and 9 patients
(14.1%) was acute and chronic ITP, respectively. Older age, absence of prior
infection and insidious onset of symptoms were significantly associated with the
development of chronic ITP. Among the patients who received IVIG, those with
platelet count <45*10(9)/L at 1 month after IVIG showed a significantly higher
incidence of chronic ITP compared to those with platelet count >=45*10(9)/L
(88.8% vs. 44.4%, P<0.01). CONCLUSION: In most patients, ITP runs a benign course
and approximately 86% of them recover within 1 year of their initial diagnosis.
The potential impact of the risk factors of chronic ITP on clinical practice
needs to be explored and further studies are warranted to determine whether IVIG
influences the course of ITP.
PMID- 27610184
TI - Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between
Apoptosis and Autophagy in PC12 Cells.
AB - Icariin (ICA), an active component of Epimedium brevicornum Maxim, exerts a
variety of neuroprotective effects such as antiapoptosis. However, the mechanisms
underlying antiapoptosis of ICA in neurons exposed to oxygen-glucose deprivation
and reperfusion (OGD/R) are unclear. The B-cell lymphoma-2 (Bcl-2) protein family
plays an important role in the regulation of apoptosis and autophagy through Bcl
2-dependent cross talk. Bcl-2 suppresses apoptosis by binding to Bax and inhibits
autophagy by binding to Beclin-1 which is an autophagy related protein. In the
present study, MTT result showed that ICA increased cell viability significantly
in OGD/R treated PC12 cells (P < 0.01). Results of western blotting analysis
showed that ICA increased Bcl-2 expression significantly and decreased
expressions of Bax, cleaved Caspase-3, Beclin-1, and LC3-II significantly in
OGD/R treated PC12 cells (P < 0.01). These results suggest that ICA protects PC12
cells from OGD/R induced autophagy via Bcl-2-dependent cross talk between
apoptosis and autophagy.
PMID- 27610185
TI - A Novel Method for Evaluating the Cardiotoxicity of Traditional Chinese Medicine
Compatibility by Using Support Vector Machine Model Combined with Metabonomics.
AB - Traditional biochemical and histopathological tests have been used to evaluate
the safety of traditional Chinese medicine (TCM) compatibility for a long time.
But these methods lack high sensitivity and specificity. In the previous study,
we have found ten biomarkers related to cardiotoxicity and established a support
vector machine (SVM) prediction model. Results showed a good sensitivity and
specificity. Therefore, in this study, we used SVM model combined with
metabonomics UPLC/Q-TOF-MS technology to build a rapid and sensitivity and
specificity method to predict the cardiotoxicity of TCM compatibility. This study
firstly applied SVM model to the prediction of cardiotoxicity in TCM
compatibility containing Aconiti Lateralis Radix Praeparata and further
identified whether the cardiotoxicity increased after Aconiti Lateralis Radix
Praeparata combined with other TCM. This study provides a new idea for studying
the evaluation of the cardiotoxicity caused by compatibility of TCM.
PMID- 27610187
TI - Evaluation of the Effects of Pinus koraiensis Needle Extracts on Serum Lipid and
Oxidative Stress in Adults with Borderline Dyslipidemia: A Randomized, Double
Blind, and Placebo-Controlled Clinical Trial.
AB - Background. Dyslipidemia has been well-known as a common metabolic disorder
contributing to cardiovascular disease. The aim of this study was to evaluate the
effect of the Pinus koraiensis needle extracts (PKE) on the blood cholesterol and
oxidative stress. Method. We conducted a 12-week randomized, double-blinded
controlled trial to examine the effect of PKE on blood lipid profiles in adults
with borderline dyslipidemia. Thirty-three eligible persons were recruited and
randomly assigned into PKE (n = 20) and placebo groups (n = 13). Serum lipids
including total cholesterol, low-density lipoprotein- (LDL-) cholesterol, high
density lipoprotein- (HDL-) cholesterol, very low-density lipoprotein- (VLDL-)
cholesterol, and triglyceride were measured before and after trial. Serum
insulin, glucose, and antioxidant indicators were also analyzed before and after
trial and anthropometry and blood pressure were measured every 4 weeks. Results.
After 12 weeks, PKE statically significant decreases in systolic blood pressure
(p < 0.05) and waist circumference (p < 0.05) were observed. Also, VLDL
cholesterol significantly decreased (from 24.4 +/- 10.0 mg/dL at baseline to 18.4
+/- 4.1 mg/dL after 12 weeks) (p < 0.05) and superoxide dismutase (SOD) increased
(6.12 +/- 0.41 U/mL to 9.06 +/- 0.62 U/mL) (p < 0.01) in PKE group. However,
after adjustment with WC, VLDL-cholesterol was not significant between groups (p
= 0.095) and while SOD remained significant between groups (p = 0.013).
Conclusion. The results show that PKE was effective in improving the superoxide
dismutase in the individuals with borderline dyslipidemia.
PMID- 27610186
TI - The Difference of Chemical Components and Biological Activities of the Crude
Products and the Salt-Processed Product from Semen Cuscutae.
AB - Semen Cuscutae is a well-known Chinese medicine which has been used to nourish
kidney in China for thousands of years. The crude product of semen Cuscutae (CP)
and its salt-processed product (SPP) are separately used in clinic for their
different effects. The study was designed to investigate the influence of
processing from semen Cuscutae on chemical components and biological effects. The
principal component analysis and quantitative analysis were used to study the
differences of the chemical components. The effects of nourishing kidney were
detected to compare the differences between the CP and SPP. The PCA results
showed that the obvious separation was achieved in the CP and SPP samples. The
results of quantitative analysis showed that quercetin and total flavonoids had
significantly increased after salt processing while hyperoside had decreased. The
comparison of CP and SPP on biological activities showed that both of them could
ameliorate the kidney-yang deficiency syndrome by restoring the level of sex
hormone, improving the immune function and antioxidant effect. However, SPP was
better in increasing the level of T and the viscera weight of testicle and
epididymis, improving the antioxidant effect. The results suggested that salt
processing changed its chemical profile, which in turn enhanced its biological
activities.
PMID- 27610188
TI - Analysis of personality traits and their influence on the quality of life of
postmenopausal women with regard to genetic factors.
AB - BACKGROUND: Quality of life can be perceived as a subjective assessment of
different aspects of human functioning. Personality is a factor which determines
actions taken by individuals and their tendency to perceive reality in a
particular way. Therefore, the assumption that personality may influence the QoL
assessment seems reasonable. Our purpose was to assess the relationships between
personality traits and the presence of the 44-bp VNTR polymorphism in the 5-HTT
(SLC 6A4) promoter region and the 30-bp VNTR polymorphism in the MAO-A promoter
region. We also wanted to determine the influence of personality on the quality
of life of postmenopausal women. METHODS: The study involved 214 postmenopausal
women from northwest Poland. It was conducted using the NEO-FFI and the SF-36
questionnaires. DNA polymorphisms were identified using the polymerase chain
reaction (PCR). RESULTS: The average age of the women was 56.8 +/- 4.08 years.
Half of the respondents had completed second-level education, 69.2 % had life
partners, and 53.3 % were professionally active. Women with the 3/3 genotype were
characterized by significantly lower openness to experience than respondents with
other MAO-A genotypes (p < 0.05). There was a significant correlation between the
quality of life and the levels of neuroticism and extroversion, as well as
between selected quality of life domains and the levels of agreeableness and
conscientiousness. CONCLUSIONS: (1)Women with the 3/3 genotype of the 30-bp VNTR
polymorphism in the MAO-A promoter region are characterized by lower levels of
openness to experience than women with other MAO-A genotypes in our study (2)
Personality traits may contribute to the assessment of the quality of life.
PMID- 27610189
TI - Quantum Phase Transitions with Parity-Symmetry Breaking and Hysteresis.
AB - Symmetry-breaking quantum phase transitions play a key role in several condensed
matter, cosmology and nuclear physics theoretical models1-3. Its observation in
real systems is often hampered by finite temperatures and limited control of the
system parameters. In this work we report for the first time the experimental
observation of the full quantum phase diagram across a transition where the
spatial parity symmetry is broken. Our system is made of an ultra-cold gas with
tunable attractive interactions trapped in a spatially symmetric double-well
potential. At a critical value of the interaction strength, we observe a
continuous quantum phase transition where the gas spontaneously localizes in one
well or the other, thus breaking the underlying symmetry of the system.
Furthermore, we show the robustness of the asymmetric state against controlled
energy mismatch between the two wells. This is the result of hysteresis
associated with an additional discontinuous quantum phase transition that we
fully characterize. Our results pave the way to the study of quantum critical
phenomena at finite temperature4, the investigation of macroscopic quantum
tunneling of the order parameter in the hysteretic regime and the production of
strongly quantum entangled states at critical points5.
PMID- 27610190
TI - Engineered Swift Equilibration of a Brownian particle.
AB - A fundamental and intrinsic property of any device or natural system is its
relaxation time relax, which is the time it takes to return to equilibrium after
the sudden change of a control parameter [1]. Reducing taurelax, is frequently
necessary, and is often obtained by a complex feedback process. To overcome the
limitations of such an approach, alternative methods based on driving have been
recently demonstrated [2, 3], for isolated quantum and classical systems [4-9].
Their extension to open systems in contact with a thermostat is a stumbling block
for applications. Here, we design a protocol, named Engineered Swift
Equilibration (ESE), that shortcuts time-consuming relaxations, and we apply it
to a Brownian particle trapped in an optical potential whose properties can be
controlled in time. We implement the process experimentally, showing that it
allows the system to reach equilibrium times faster than the natural
equilibration rate. We also estimate the increase of the dissipated energy needed
to get such a time reduction. The method paves the way for applications in micro
and nano devices, where the reduction of operation time represents as substantial
a challenge as miniaturization [10].
PMID- 27610191
TI - Fully Automated Lipid Pool Detection Using Near Infrared Spectroscopy.
AB - Background. Detecting and identifying vulnerable plaque, which is prone to
rupture, is still a challenge for cardiologist. Such lipid core-containing plaque
is still not identifiable by everyday angiography, thus triggering the need to
develop a new tool where NIRS-IVUS can visualize plaque characterization in terms
of its chemical and morphologic characteristic. The new tool can lead to the
development of new methods of interpreting the newly obtained data. In this
study, the algorithm to fully automated lipid pool detection on NIRS images is
proposed. Method. Designed algorithm is divided into four stages: preprocessing
(image enhancement), segmentation of artifacts, detection of lipid areas, and
calculation of Lipid Core Burden Index. Results. A total of 31 NIRS chemograms
were analyzed by two methods. The metrics, total LCBI, maximal LCBI in 4 mm
blocks, and maximal LCBI in 2 mm blocks, were calculated to compare presented
algorithm with commercial available system. Both intraclass correlation (ICC) and
Bland-Altman plots showed good agreement and correlation between used methods.
Conclusions. Proposed algorithm is fully automated lipid pool detection on near
infrared spectroscopy images. It is a tool developed for offline data analysis,
which could be easily augmented for newer functions and projects.
PMID- 27610192
TI - Molecular analysis of human Papillomavirus detected among women positive for
cervical lesions by visual inspection with acetic acid/Lugol's iodine (VIA/VILI)
in Libreville, Gabon.
AB - BACKGROUND: The human papillomavirus (HPV) is the causative agent of cervical
cancer, which is the leading cancer-related cause of death for women in Sub
Saharan Africa. In 2013, the Gabonese Ministry of Health and the Sylvia Bongo
Ondimba Foundation implemented cervical cancer screening programs based on the
detection of cancerous lesions by visual inspection with acetic acid and/or
Lugol's iodine (VIA/VILI). This pilot study was set up to determine the HPV
profile and analyze the nucleotide sequence variation of HPV16 circulating in
patients with cervical abnormalities detected by VIA/VILI testing. METHODS: The
cervical abnormalities observed upon VIA/VILI were confirmed by liquid-based
cytology for all tested women. Nested PCR using the MY09/11 and GP5+/6+ primer
sets was used to detect HPVs present in the extracted DNA. HPV genotypes were
determined after sequencing of amplicons based on a high-throughput sequencing
approach. For isolates of the HPV16 genotype, the E6 gene and the long control
region (LCR) were directly sequenced using Sanger method. RESULTS: The study
included 87 women who showed a positive VIA/VILI result. Cervical abnormalities
were found in 40.23 % of women and 40 % were classified as high-grade lesions.
The HPV detection rate was 82.9 % among women with abnormal cytology. Among all
the identified high-risk HPV genotypes, HPV16, 18 and 33 were the most frequent.
Multiple HPV infections were observed in 42.31 % of HPV-infected women. Analysis
of the HPV16 sequence variation in the E6 gene and in the LCR showed that 85.3
and 14.7 % belonged to the African and European lineages, respectively. Among the
African branch variants, Af2 was the most frequently identified in this study.
CONCLUSION: This study offers the first report of the HPV detection rate and
molecular epidemiology among Gabonese women with a positive result in a VIA/VILI
screening test. Moreover, data on the HPV16 sequence variation confirm the
predominance of African variants in high-grade lesions.
PMID- 27610193
TI - Children's palliative care now! Highlights from the second ICPCN conference on
children's palliative care, 18-21 May 2016, Buenos Aires, Argentina.
AB - The International Children's Palliative Care Network held its second
international conference on children's palliative care in Buenos Aires,
Argentina, from the 18th-21st May 2016. The theme of the conference was
'Children's Palliative Care.... Now!' emphasising the need for palliative care
for children now, as the future will be too late for many of them. Six pre
conference workshops were held, addressing issues connected to pain assessment
and management, adolescent palliative care, ethics and decision-making,
developing programmes, the basics of children's palliative care, and hidden
aspects of children's palliative care. The conference brought together 410
participants from 40 countries. Plenary, concurrent, and poster presentations
covered issues around the status of children's palliative care, genetics,
perinatal and neonatal palliative care, the impact of children's palliative care
and the experiences of parents and volunteers, palliative care as a human right,
education in children's palliative care, managing complex pain in children,
spiritual care and when to initiate palliative care. The 'Big Debate' explored
issues around decision-making and end of life care in children, and gave
participants the opportunity to explore a sensitive and thought provoking topic.
At the end of the conference, delegates were urged to sign the Commitment of
Buenos Aires which called for governments to implement the WHA resolution and
ensure access to palliative care for neonates, children and their families, and
also commits us as palliative care providers to share all that we can and
collaborate with each other to achieve the global vision of palliative care for
all children who need it. The conference highlighted the ongoing issues in
children's palliative care and participants were continually challenged to ensure
that children can access palliative care NOW.
PMID- 27610194
TI - Small cell neuroendocrine tumour of the endometrium and the importance of
pathologic diagnosis.
AB - Small cell carcinoma of the endometrium is a very rare entity. They are very
aggressive tumours, with a poor prognosis. They represent a clinical challenge
because of a lack of a standardised treatment. We see here a case of a 67-year
old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After
presenting with postmenopausal vaginal bleeding in October 2014, she underwent a
hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A
hysterectomy and bilateral oophorectomy was performed because of uncontrolled
uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the
endometrium. A surgical complete cytoreduction was achieved after the case being
presented in a multidisciplinary tumour board. Pathologic results revealed
metastasis from peritoneal implants of SCC on the endometrium, and metastasis in
pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A
total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m2 day
one) and etoposide (100mg/m2 day one, two, three) every 21 days was given. The
patient experienced persistent disease and died 17 months after the diagnosis.
SCC of the endometrium is a very rare and aggressive disease that requires an
individualised multidisciplinary management.
PMID- 27610195
TI - Highlights from the 2016 WIN Symposium, 27-29 June 2016, Paris: personalised
therapy beyond next-generation sequencing.
AB - The Worldwide Innovative Networking (WIN) consortium is an alliance of academic
institutions, pharmaceutical partners, representatives from technology companies
and charitable/health payer organisations from across the globe. For the last six
years, the consortium's aims have been to foster communication and collaboration
between members, encourage dialogue in an open forum, and deliver clinical trial
results that improve the care and outcomes of patients with cancer using the
latest advances in genomic-based medicine. The annual WIN Symposium, held over
two days, is a chance for its members to come together and discuss ongoing
research, recent announcements, and introduce new developments in personalised
medicine. This year's conference, held in Paris, France 27-29 June, consisted of
six dedicated sessions, including two debates, and posters from members and
participating organisations, all focusing on the latest therapeutic advances and
updates in genomic analysis. Special highlights from this year included
discussion of the MINDACT clinical trial, which uses a gene expression test to
identify patients with breast cancer who can safely forego adjuvant chemotherapy,
and the reflections on the SHIVA trial. Of particular interest to many speakers
was the utilisation of liquid biopsy samples to produce near real time snapshots
of tumour mutational profiles and vulnerability.
PMID- 27610196
TI - Maps and atlases of cancer mortality: a review of a useful tool to trigger new
questions.
AB - In this review we illustrate our view on the epidemiological relevance of
geographically mapping cancer mortality. In the first part of this work, after
delineating the history of cancer mapping with a view on interpretation of Cancer
Mortality Atlases, we briefly illustrate the 'art' of cancer mapping. Later we
summarise in a non-mathematical way basic methods of spatial statistics. In the
second part of this paper, we employ the 'Atlas of Cancer Mortality in the
European Union and the European Economic Area 1993-1997' in order to illustrate
spatial aspects of cancer mortality in Europe. In particular, we focus on the
cancer related to tobacco and alcohol epidemics and on breast cancer which is of
particular interest in cancer mapping. Here we suggest and reiterate two key
concepts. The first is that a cancer atlas is not only a visual tool, but it also
contain appropriate spatial statistical analyses that quantify the qualitative
visual impressions to the readers even though at times revealing fallacy. The
second is that a cancer atlas is by no means a book where answers to questions
can be found. On the contrary, it ought to be considered as a tool to trigger new
questions.
PMID- 27610197
TI - Outcome of radical prostatectomy in primary circulating prostate cell negative
prostate cancer.
AB - INTRODUCTION: Around 90% of prostate cancers detected using the serum prostate
specific antigen (PSA) as a screening test are considered to be localised.
However, 20-30% of men treated by radical prostatectomy experience biochemical
failure within two years of treatment. The presence of primary circulating
prostate cells (CPCs) in the blood of these men implies a dissemination of the
tumour and could indicate a greater risk of treatment failure. OBJECTIVE: To
evaluate the use of the number of primary CPCs detected before surgery in the
prediction of biochemical failure at ten years. HYPOTHESIS: The dissemination of
cancer cells to distant sites will determine the patient's prognosis. The absence
of primary CPCs in men undergoing radical prostatectomy for prostate cancer may
imply a less aggressive disease and therefore could be utilised as a prognostic
factor to predict biochemical failure after surgery. METHODS AND PATIENTS: A
single-centre observational study of a cohort of 285 men who underwent radical
prostatectomy as monotherapy for prostate cancer, in whom the number of CPCs
prior to treatment was determined, and who were followed up for ten years to
determine biochemical failure. A Cox proportional risks with polynomial fractions
analysis was used to predict biochemical failure based on the number of primary
CPCs detected. A decision curve analysis was performed for the model obtained.
RESULTS: Kaplan-Meier curves for biochemical free survival at ten years was
47.34% (95% CI 38.71-55.48%). It is important to note that in CPC negative men,
the ten years Kaplan-Meier biochemical-free survival was 90.35% (95% CI 75.0
96.27) whereas in men who were primary CPC positive, the biochemical free
survival rate was 30.00% (95% CI 20.34-40.60%). The Coxs'model to predict
biochemical failure using transformed data with a power of minus one for the
number of primary CPCs detected, showed a Harrell's C concordance index of 0.74
and a decision analysis curve showing a net benefit of CPC detection over other
risk factors to predict biochemical failure. CONCLUSIONS: The number of primary
CPCs detected before surgery permits a good prediction of subsequent biochemical
failure in men undergoing radical prostatectomy as monotherapy for prostate
cancer. Men negative for primary CPCs have a biochemical-free survival of over
90% at ten years and should be considered for curative surgery.
PMID- 27610198
TI - Highlights from the 1st Latin American meeting on metronomic chemotherapy and
drug repositioning in oncology, 27-28 May, 2016, Rosario, Argentina.
AB - Following previous metronomic meetings in Marseille (2011), Milano (2014), and
Mumbai (2016), the first Latin American metronomic meeting was held in the School
of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and
28 of May, 2016. For the first time, clinicians and researchers with experience
in the field of metronomics, coming from different countries in Latin America,
had the opportunity of presenting and discussing their work. The talks were
organised in three main sessions related to experience in the pre-clinical, and
clinical (paediatric and adult) areas. The different presentations demonstrated
that the fields of metronomic chemotherapy and repurposing drugs in oncology,
known as metronomics, constitute a branch of cancer therapy in permanent
evolution, which have strong groups working in Latin America, both in the
preclinical and the clinical settings including large, adequately designed
randomised studies. It was shown that metronomics offers treatments, which,
whether they are combined or not with the standard therapeutic approaches, are
not only effective but also minimally toxic, with the consequent improvement of
the patient's quality of life, and inexpensive, a feature very important in low
resource clinical settings. The potential use of metronomic chemotherapy was
proposed as a cost/effective treatment in low-/middle-income countries, for
adjuvant therapy in selected tumours. The fundamental role of the governmental
agencies and non-governmental alliances, as the Metronomic Global Health
Initiative, in supporting this research with public interest was underlined.
PMID- 27610200
TI - Adoptive cell therapy and modulation of the tumour microenvironment: new insights
from ASCO 2016.
AB - Immuno-oncology has changed the landscape of cancer treatment in recent years.
Immune checkpoint inhibitors (ICI) have shown survival advantage with long term
remissions in a variety of cancers. However, there is another approach to
harnessing the power of the immune system in combating cancer: the adoptive cell
therapy (ACT) strategy. Although ACT is restricted to small specialized centres
and has yet to deliver as much success as ICI, some important results were
presented at this year's ASCO meeting. Important lessons have been learned from
these studies, including the prospects and challenges ahead. In this editorial,
we summarize the important studies on ACT presented at the ASCO 2016 meeting and
discuss the way forward.
PMID- 27610199
TI - Simple trachelectomy during pregnancy for cervical cancer.
AB - Invasive cervical cancer is rare during a pregnancy, even though it is one of the
most frequently diagnosed neoplasias during that time. It is noted that around
30% of women diagnosed with cervical cancer are of reproductive age. This means
that up to 3% of cases of cervical cancer are found in pregnant women or those
who are in the post-birth period. A cervicovaginal Pap smear is performed as part
of the regular checkup for a pregnant woman during the first visit so that
cervical cancer can easily be diagnosed early in these women, detecting it early
in up to 70-80% of cases. We present here the case of a patient with initial
diagnosis of cervical cancer made around 20th week of pregnancy. It was then
treated by a simple trachelectomy and cerclage during week 24. The pregnant woman
gave birth to a healthy baby at the end of her pregnancy. Definitive treatment
was completed three months after giving birth with a total hysterectomy and
laparoscopic bilateral salpingectomy while preserving both ovaries. After 17
months of monitoring the patient showed no signs of reoccurrence. In conclusion,
during the early stage of cervical cancer conservative management may be a
reasonable option to preserve the current pregnancy.
PMID- 27610201
TI - Comparison of awareness about precautions for needle stick injuries: a survey
among health care workers at a tertiary care center in Pakistan.
AB - BACKGROUND: Needle stick injuries (NSIs) have the potential of causing Hepatitis
B and Hepatitis C, which is constantly adding to the burden of chronic liver
disease in our country. It poses a risk to Health Care Workers (HCWs) and the
patients they deal with. In order to limit the spread of these viruses, it is
imperative that these HCWs be fully equipped with knowledge regarding prevention
of NSIs and dealing with one, regardless of their designation. We therefore aimed
to assess and compare the level of awareness about precautions for needle stick
injuries amongst all those greatest at risk. METHODS: This was a cross- sectional
study carried out at Liaquat National Hospital, Karachi, Pakistan. A 23 itemed
self-administered questionnaire was given to hospital staff including doctors,
lab technicians and nurses via convenience sampling, in various departments. Data
was analyzed via SPSS 18 software and a p-value of <0.05 was considered
significant. RESULTS: A total of 198 responses were taken for this study, out of
which 70 (35.4 %) were doctors, 70 (35.4 %) nursing staff and 58 (29.3 %)
laboratory technicians. Of all HCWs, 101 (51 %) knew that the standard method of
discarding needles is without recapping. 159 (80.3 %) were still recapping
needles. 180 (90.9 %) HCWs were vaccinated against Hepatitis B. 36 (18.2 %) were
aware that blood should be allowed to flow after an NSI and site of prick should
be washed with an antiseptic. CONCLUSION: The awareness was found to be very low
amongst all HCWs. It should therefore be made compulsory for all HCWs to attend
proper preparatory classes by the infection control department at the time of
employment in order to improve the level of awareness and ensure safe practices.
PMID- 27610202
TI - Enlarged NT (>=3.5 mm) in the first trimester - not all chromosome aberrations
can be detected by NIPT.
AB - BACKGROUND: Since non-invasive prenatal testing (NIPT) in maternal blood became
available, we evaluated which chromosome aberrations found in our cohort of
fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP
microarray) could be detected by NIPT as well. METHOD: 362 fetuses were referred
for cytogenetic testing due to an enlarged NT (>=3.5 mm). Chromosome aberrations
were investigated using QF-PCR, karyotyping and whole genome SNP array. RESULTS:
After invasive testing a chromosomal abnormality was detected in 137/362 (38 %)
fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an
aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a
pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8
%) a susceptibility locus for neurodevelopmental disorders was found. We
estimated that in 2-10 % of fetuses with enlarged NT a chromosome aberration
would be missed by current NIPT approaches. CONCLUSION: Based on our cohort of
fetuses with enlarged NT we may conclude that NIPT, depending on the approach,
will miss chromosome aberrations in a significant percentage of pregnancies.
Moreover all abnormal NIPT results require confirmatory studies with invasive
testing, which will delay definitive diagnosis in ca. 30 % of patients. These
figures are important for pretest counseling enabling pregnant women to make
informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged
NT should be investigated to assess the additional diagnostic value of high
resolution array testing for this indication.
PMID- 27610203
TI - Environmental and resource burdens associated with world biofuel production out
to 2050: footprint components from carbon emissions and land use to waste
arisings and water consumption.
AB - Environmental or 'ecological' footprints have been widely used in recent years as
indicators of resource consumption and waste absorption presented in terms of
biologically productive land area [in global hectares (gha)] required per capita
with prevailing technology. In contrast, 'carbon footprints' are the amount of
carbon (or carbon dioxide equivalent) emissions for such activities in units of
mass or weight (like kilograms per functional unit), but can be translated into a
component of the environmental footprint (on a gha basis). The carbon and
environmental footprints associated with the world production of liquid biofuels
have been computed for the period 2010-2050. Estimates of future global biofuel
production were adopted from the 2011 International Energy Agency (IEA)
'technology roadmap' for transport biofuels. This suggests that, although first
generation biofuels will dominate the market up to 2020, advanced or second
generation biofuels might constitute some 75% of biofuel production by 2050. The
overall environmental footprint was estimated to be 0.29 billion (bn) gha in 2010
and is likely to grow to around 2.57 bn gha by 2050. It was then disaggregated
into various components: bioproductive land, built land, carbon emissions,
embodied energy, materials and waste, transport, and water consumption. This
component-based approach has enabled the examination of the Manufactured and
Natural Capital elements of the 'four capitals' model of sustainability quite
broadly, along with specific issues (such as the linkages associated with the so
called energy-land-water nexus). Bioproductive land use was found to exhibit the
largest footprint component (a 48% share in 2050), followed by the carbon
footprint (23%), embodied energy (16%), and then the water footprint (9%).
Footprint components related to built land, transport and waste arisings were all
found to account for an insignificant proportion to the overall environmental
footprint, together amounting to only about 2.
PMID- 27610204
TI - Prevalence of diabetes in Brazil over time: a systematic review with meta
analysis.
AB - Diabetes is one of the most important epidemic diseases of this century and the
number of people with diabetes has more than doubled over the past three decades.
Our aim was to estimate the prevalence of diabetes in the adult Brazilian
population and analyze the trends for the last three decades through a systematic
review with meta-analysis. This review included observational studies published
between 1980 and 2015, which were independently identified by two reviewers in
five databases. Random effect models were used to estimate the prevalence and
trends of diabetes. In total, 50 articles were included in this review. Three
different patterns for diabetes diagnosis were identified: self-report (36
studies), fasting glucose (7 studies), and complex diagnosis (fasting glucose,
oral glucose tolerance test, and self-report; 7 studies). The prevalence of
diabetes was 5.6 % (95 % CI 5.0-6.3; I(2) = 100 %) by self-report, 6.6 % (95 % CI
4.8-8.9; I(2) = 94 %) by fasting glucose, and 11.9 % (95 % CI 7.7-17.8 I(2) = 100
%) by complex diagnosis. In trend analyses, we observed an increase in the
prevalence of diabetes over time. The biggest increase was detected in studies
using complex diagnosis: 7.4 % (95 % CI 7.1-7.7) in the 1980s to 15.7 % (95 % CI
9.8-24.3) in the 2010s. In conclusion, despite high heterogeneity, this study
observed a high prevalence of diabetes in Brazilian adults over time and with a
progressive increase in the last 35 years.
PMID- 27610205
TI - Antidepressant medication during pregnancy and epigenetic changes in umbilical
cord blood: a systematic review.
AB - INTRODUCTION: Epigenetic mechanisms are important for the regulation of gene
expression and differentiation in the fetus and the newborn child. Symptoms of
maternal depression and antidepressant use affects up to 20 % of pregnant women,
and may lead to epigenetic changes with life-long impact on child health. The aim
of this review is to investigate whether there is an association between exposure
to maternal antidepressants during pregnancy and epigenetic changes in the
newborn. MATERIAL AND METHODS: Systematic literature searches were performed in
MEDLINE and EMBASE combining MeSH terms covering epigenetic changes, use of
antidepressant medication, pregnancy and newborns. A keyword search was also
performed. We included studies on pregnant women and their children where there
was a history of maternal depressed mood or anxiety, a reported use of
antidepressant medication, and measurements of epigenetic changes in umbilical
cord blood. Studies using genome-wide or candidate-based epigenetic analyses were
included. Citations and references from the included articles were investigated
to locate further relevant articles. The completeness of reporting as well as the
risk of bias and confounding was assessed. RESULTS: Six studies were included.
They all investigated methylation changes. Genome-wide methylation changes were
examined in 184 children and methylation status in specific genes was examined in
96 children exposed to antidepressant medication. Three of the studies found an
association between use of antidepressant medication during pregnancy and
methylation status at various CpG sites measured in cord blood of the newborn.
One of these studies found an association in African-Americans, but not
Caucasians. The remaining three studies found associations between maternal mood
and epigenetic changes in umbilical cord blood but no association between
epigenetic changes and maternal use of antidepressant medication. CONCLUSION: The
included studies have not established a clear association between use of
antidepressant medication during pregnancy and epigenetic changes in the cord
blood. Future studies using newer, more wide-ranging epigenetic methods could
discover possible new differentially methylated sites. Larger sample sizes and
good validity of exposures are warranted in order to adjust for level of maternal
depression, other maternal illness, maternal use of other types of medication,
and maternal ethnicity. PROSPERO registration number: CRD42015026575.
PMID- 27610206
TI - Aberrant methylation of cell-free circulating DNA in plasma predicts poor outcome
in diffuse large B cell lymphoma.
AB - BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free
circulating DNA in plasma has not previously been evaluated in diffuse large B
cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant
promoter DNA methylation can be detected in plasma from DLBCL patients and to
evaluate this as a prognostic marker. Furthermore, we wanted to follow possible
changes in methylation levels during treatment. Seventy-four patients were
enrolled in the study, of which 59 received rituximab and CHOP-like chemotherapy.
Plasma samples were collected from all patients at the time of diagnosis and from
14 healthy individuals used as controls. In addition, plasma samples were
collected during and after treatment for surviving patients. In total, 158 plasma
samples were analyzed for DNA methylation in the promoter regions of DAPK
(DAPK1), DBC1, MIR34A, and MIR34B/C using pyrosequencing. RESULTS: Aberrant
methylation levels at the time of diagnosis were detected in 19, 16, 8, and 10 %
of the DLBCL plasma samples for DAPK1, DBC1, MIR34A, and MIR34B/C, respectively.
DAPK1 methylation levels were significantly correlated with DBC1 and MIR34B/C
methylation levels (P < 0.001). For the entire cohort, 5-year overall survival
(OS) rates were significantly lower in the groups carrying aberrant DAPK1 (P =
0.004) and DBC1 (P = 0.044) methylation, respectively. DAPK1 methylation status
were significantly correlated with stage (P = 0.015), as all patients with
aberrant DAPK1 methylation were stages III and IV. Multivariate analysis
identified DAPK1 as an independent prognostic factor for OS with a hazard ratio
of 8.9 (95 % CI 2.7-29.3, P < 0.0007). Patients with DAPK1 methylated cell-free
circulating DNA at time of diagnosis, who became long-term survivors, lost the
aberrant methylation after treatment initiation. Conversely, patients that
maintained or regained aberrant DAPK1 methylation died soon thereafter.
CONCLUSIONS: Aberrant promoter methylation of cell-free circulating DNA can be
detected in plasma from DLBCL patients and hold promise as an easily accessible
marker for evaluating response to treatment and for prognostication. In
particular, aberrant DAPK1 methylation in plasma was an independent prognostic
marker that may also be used to assess treatment response.
PMID- 27610208
TI - Free Energy of Ligand Removal in the Metal-Organic Framework UiO-66.
AB - We report an investigation of the "missing-linker phenomenon" in the Zr-based
metal-organic framework UiO-66 using atomistic force field and quantum chemical
methods. For a vacant benzene dicarboxylate ligand, the lowest energy charge
capping mechanism involves acetic acid or Cl-/H2O. The calculated defect free
energy of formation is remarkably low, consistent with the high defect
concentrations reported experimentally. A dynamic structural instability is
identified for certain higher defect concentrations. In addition to the changes
in material properties upon defect formation, we assess the formation of
molecular aggregates, which provide an additional driving force for ligand loss.
These results are expected to be of relevance to a wide range of metal-organic
frameworks.
PMID- 27610209
TI - DC Electroacupuncture Effects on Scars and Sutures of a Patient with
Postconcussion Pain.
AB - Introduction: This case study offers a detailed comparative analysis of the
effects of direct-current electroacupuncture (DC-EA) on the autonomic nervous
system (ANS), when DC-EA was applied to the cranial sutures and scars of a
patient with a history of ischemic stroke and postconcussion syndrome (PCS) pain.
Case: A 56-year-old female suffering from severe tremors and debilitating
headaches requested acupuncture after conventional biomedicines failed to relieve
her symptoms. Evaluations were performed to check the status of 27 ANS functions.
These detailed evaluations were performed to obtain a baseline status of ANS
function on this patient, who had a history of ischemic stroke, PCS, and chronic
pain. All evaluations were repeated pre-post her DC-EA treatment. Results: This
patient experienced significant relief from her symptoms after DC-EA treatment.
An analysis of this patient's risk for ANS complications showed improvements in
four key homeostatic markers post treatment. Conclusions: The ANS response of a
patient with ischemic stroke, PCS, and chronic pain, who received electrical
nerve stimulation using DC-EA reflected a measurable improvement in sympathetic
tone, along with reductions in pain levels and PCS symptoms. The positive results
in this case study could have applications to other pathologies that can be
affected by the sympathetic nervous system activation on the body.
PMID- 27610210
TI - Lunate Dislocation and Basic Wrist Kinematics.
PMID- 27610207
TI - The Management of the Pediatric Neurogenic Bladder.
AB - Neurogenic bladder is a heterogeneous entity that may result from a variety of
conditions affecting the central or peripheral nervous systems. Regardless of
etiology, the overall goals of management are primarily twofold. As a neurogenic
bladder may affect the ability to store urine safely and to empty the bladder
efficiently, early management is focused on optimization of bladder storage
function to prevent irreversible injury to either the upper or lower urinary
tracts. In older children, this goal is added to the challenge of maximizing
quality of life through achievement of urinary continence and independence in
bladder management that continues into the transition to adulthood. In this
review, we seek to bring the reader up-to-date regarding management of the
pediatric neurogenic bladder with a focus on literature published in the past
year. We discuss key contributions related to fetal intervention for
myelomeningocele, monitoring and medical management of the neurogenic bladder and
prediction of postoperative outcomes. Put together, these studies highlight the
continued need for further research to improve evidence-based medical and
surgical decision-making strategies for children affected by neurogenic bladder.
PMID- 27610212
TI - Complete genome sequence of Halomonas sp. R5-57.
AB - The marine Arctic isolate Halomonas sp. R5-57 was sequenced as part of a
bioprospecting project which aims to discover novel enzymes and organisms from
low-temperature environments, with potential uses in biotechnological
applications. Phenotypically, Halomonas sp. R5-57 exhibits high salt tolerance
over a wide range of temperatures and has extra-cellular hydrolytic activities
with several substrates, indicating it secretes enzymes which may function in
high salinity conditions. Genome sequencing identified the genes involved in the
biosynthesis of the osmoprotectant ectoine, which has applications in food
processing and pharmacy, as well as those involved in production of
polyhydroxyalkanoates, which can serve as precursors to bioplastics. The
percentage identity of these biosynthetic genes from Halomonas sp. R5-57 and
current production strains varies between 99 % for some to 69 % for others, thus
it is plausible that R5-57 may have a different production capacity to currently
used strains, or that in the case of PHAs, the properties of the final product
may vary. Here we present the finished genome sequence (LN813019) of Halomonas
sp. R5-57 which will facilitate exploitation of this bacterium; either as a whole
cell production host, or by recombinant expression of its individual enzymes.
PMID- 27610213
TI - Draft genome sequence of Enterococcus faecium strain LMG 8148.
AB - Enterococcus faecium, traditionally considered a harmless gut commensal, is
emerging as an important nosocomial pathogen showing increasing rates of
multidrug resistance. We report the draft genome sequence of E. faecium strain
LMG 8148, isolated in 1968 from a human in Gothenburg, Sweden. The draft genome
has a total length of 2,697,490 bp, a GC-content of 38.3 %, and 2,402 predicted
protein-coding sequences. The isolation of this strain predates the emergence of
E. faecium as a nosocomial pathogen. Consequently, its genome can be useful in
comparative genomic studies investigating the evolution of E. faecium as a
pathogen.
PMID- 27610214
TI - Draft genome sequence of Lampropedia cohaerens strain CT6(T) isolated from
arsenic rich microbial mats of a Himalayan hot water spring.
AB - Lampropedia cohaerens strain CT6(T), a non-motile, aerobic and coccoid strain was
isolated from arsenic rich microbial mats (temperature ~45 degrees C) of a hot
water spring located atop the Himalayan ranges at Manikaran, India. The present
study reports the first genome sequence of type strain CT6(T) of genus
Lampropedia cohaerens. Sequencing data was generated using the Illumina HiSeq
2000 platform and assembled with ABySS v 1.3.5. The 3,158,922 bp genome was
assembled into 41 contigs with a mean GC content of 63.5 % and 2823 coding
sequences. Strain CT6(T) was found to harbour genes involved in both the Entner
Duodoroff pathway and non-phosphorylated ED pathway. Strain CT6(T) also contained
genes responsible for imparting resistance to arsenic, copper, cobalt, zinc,
cadmium and magnesium, providing survival advantages at a thermal location.
Additionally, the presence of genes associated with biofilm formation,
pyrroloquinoline-quinone production, isoquinoline degradation and mineral
phosphate solubilisation in the genome demonstrate the diverse genetic potential
for survival at stressed niches.
PMID- 27610211
TI - Creatine Prevents the Structural and Functional Damage to Mitochondria in
Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation
Capacity.
AB - Creatine (Cr) is a nutritional supplement promoting a number of health benefits.
Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy,
improve rehabilitation, and afford mild antioxidant activity. The beneficial
effects are likely to derive from pleiotropic interactions. In accord with this
notion, we previously demonstrated that multiple pleiotropic effects, including
preservation of mitochondrial damage, account for the capacity of Cr to prevent
the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given
the importance of mitochondria in supporting the myogenic process, here we
further explored the protective effects of Cr on the structure, function, and
networking of these organelles in C2C12 cells differentiating under oxidative
stressing conditions; the effects on the energy sensor AMPK, on PGC-1alpha, which
is involved in mitochondrial biogenesis and its downstream effector Tfam were
also investigated. Our results indicate that damage to mitochondria is crucial in
the differentiation imbalance caused by oxidative stress and that the Cr
prevention of these injuries is invariably associated with the recovery of the
normal myogenic capacity. We also found that Cr activates AMPK and induces an
upregulation of PGC-1alpha expression, two events which are likely to contribute
to the protection of mitochondrial quality and function.
PMID- 27610216
TI - Thanking cell and bioscience reviewers.
PMID- 27610215
TI - Social affiliation motives modulate spontaneous learning in Williams syndrome but
not in autism.
AB - BACKGROUND: Children with autism spectrum disorder (ASD) and those with Williams
syndrome (WS) have difficulties with learning, though the nature of these remains
unclear. METHODS: In this study, we used novel eye-tracking and behavioral
paradigms to measure how 36 preschoolers with ASD and 21 age- and IQ-matched
peers with WS attend to and learn novel behaviors (1) from the outcomes of their
own actions (non-social learning), (2) through imitation of others' actions
(social learning), and across situations in which imitative learning served
either an instrumental function or fulfilled social affiliation motives. RESULTS:
The two groups demonstrated similar abilities to learn from the consequences of
their own actions and to imitate new actions that were instrumental to the
achievement of a tangible goal. Children with WS, unlike those with ASD,
increased their attention and imitative learning performance when the model acted
in a socially engaging manner. CONCLUSIONS: Learning abnormalities in ASD appear
to be linked to the social rather than instrumental dimensions of learning.
PMID- 27610217
TI - Cost utility analysis of the SQ((r)) HDM SLIT-tablet in house dust mite allergic
asthma patients in a German setting.
AB - BACKGROUND: Asthma affects an estimated 300 million people worldwide with the
condition associated with significant healthcare utilisation costs and a large
impact on patient quality of life. The SQ((r)) HDM SLIT-tablet (ACARIZAX((r)),
Horsholm, Denmark) is a sublingually administered allergy immunotherapy tablet
for house dust mite allergic asthma and allergic rhinitis and has recently been
licensed in Europe. OBJECTIVE: To assess the cost-effectiveness of ACARIZAX plus
pharmacotherapy versus placebo plus pharmacotherapy in patients with house dust
mite allergic asthma that is uncontrolled by inhaled corticosteroids, in a German
setting. Eligible patients should also have symptoms of mild to severe allergic
rhinitis. METHODS: A cost utility analysis was undertaken, based on the results
of a European phase III randomised controlled trial, in which ACARIZAX was
compared with placebo with both treatment groups also receiving pharmacotherapy
in the form of inhaled corticosteroids and short-acting beta2-agonists. Cost and
quality-adjusted life years from the trial were extrapolated over a nine year
time horizon and the incremental cost-effectiveness ratio calculated to compare
treatment options. RESULTS: ACARIZAX plus pharmacotherapy was estimated to
generate 6.16 quality-adjusted life years per patient at a cost of ?5658,
compared with 5.50 quality-adjusted life years (QALYs) at a cost of ?2985 for
placebo plus pharmacotherapy. This equated to an incremental cost of ?2673,
incremental QALYs of 0.66 and an incremental cost-effectiveness ratio (ICER) of
?4041. The ICER was, therefore, substantially lower than the ?40,000 willingness
to-pay threshold per QALY adopted for the analysis. Deterministic sensitivity
analyses indicate the results are most sensitive to the utility score of ACARIZAX
patients during years 2 and 3 of treatment. CONCLUSION: This analysis indicates
that ACARIZAX plus pharmacotherapy is cost-effective compared with placebo plus
pharmacotherapy for house dust mite allergic asthma patients in Germany. If a
disease-modifying effect can be proven the results of this analysis may
underestimate the true benefits of ACARIZAX.
PMID- 27610219
TI - Detecting variable responses within fMRI time-series of volumes-of-interest using
repeated measures ANOVA.
AB - We present an approach to analyzing fMRI timetrends from volumes-of-interest
(VOI) within and between subject groups using repeated measures analysis of
variance (RMANOVA), which allows temporal patterns to be examined without an a
priori model of expected timing or pattern of response. The method serves as a
complement to whole-brain voxel-based analyses, and is useful for detecting
complex responses within pre-determined brain regions, or as a post-hoc analysis
of regions of interest identified by whole-brain assessments. We illustrate an
implementation of the technique in the statistical software package SAS. VOI
timetrends are extracted from conventionally preprocessed fMRI images. A
timetrend of average signal intensity across the VOI during the scanning period
is calculated for each subject. The values are scaled relative to baseline
periods, imported into SAS, and the procedure PROC MIXED implements the RMANOVA.
The ensuing results allow determination of significant overall effects, and time
point specific within- and between-group responses relative to baseline. We
illustrate the technique using fMRI data from two groups of subjects who
underwent a respiratory challenge. RMANOVA allows insight into the timing of
responses and response differences between groups, and so is suited to fMRI
paradigms eliciting complex response patterns.
PMID- 27610218
TI - Factors affecting return to work after injury or illness: best evidence synthesis
of systematic reviews.
AB - BACKGROUND: Work disability is a major personal, financial and public health
burden. Predicting future work success is a major focus of research. OBJECTIVES:
To identify common prognostic factors for return-to-work across different health
and injury conditions and to describe their association with return-to-work
outcomes. METHODS: Medline, Embase, PsychINFO, Cinahl, and Cochrane Database of
Systematic Reviews and the grey literature were searched from January 1, 2004 to
September 1, 2013. Systematic reviews addressing return-to-work in various
conditions and injuries were selected. Eligible studies were critically appraised
using the Scottish Intercollegiate Guidelines Network criteria to identify low
risk of bias reviews. RESULTS: Of the 36,193 titles screened and the 94 eligible
studies reviewed, 56 systematic reviews were accepted as low risk of bias. Over
half of these focused on musculoskeletal disorders, which were primarily spine
related (e.g., neck and low back pain). The other half of studies assessed
workers with mental health or cardiovascular conditions, stroke, cancer, multiple
sclerosis or other non-specified health conditions. Many factors have been
assessed, but few consistently across conditions. Common factors associated with
positive return-to-work outcomes were higher education and socioeconomic status,
higher self-efficacy and optimistic expectations for recovery and return-to-work,
lower severity of the injury/illness, return-to-work coordination, and
multidisciplinary interventions that include the workplace and stakeholders.
Common factors associated with negative return-to-work outcomes were older age,
being female, higher pain or disability, depression, higher physical work
demands, previous sick leave and unemployment, and activity limitations.
CONCLUSIONS: Expectations of recovery and return-to-work, pain and disability
levels, depression, workplace factors, and access to multidisciplinary resources
are important modifiable factors in progressing return-to-work across health and
injury conditions. Employers, healthcare providers and other stakeholders can use
this information to facilitate return-to-work for injured/ill workers regardless
of the specific injury or illness. Future studies should investigate novel
interventions, and other factors that may be common across health conditions.
PMID- 27610220
TI - An assay to measure poly(ADP ribose) glycohydrolase (PARG) activity in cells.
AB - After a DNA damage signal multiple polymers of ADP ribose attached to poly(ADP)
ribose (PAR) polymerases (PARPs) are broken down by the enzyme poly(ADP) ribose
glycohydrolase (PARG). Inhibition of PARG leads to a failure of DNA repair and
small molecule inhibition of PARG has been a goal for many years. To determine
whether biochemical inhibitors of PARG are active in cells we have designed an
immunofluorescence assay to detect nuclear PAR after DNA damage. This 384-well
assay is suitable for medium throughput high-content screening and can detect
cell-permeable inhibitors of PARG from nM to uM potency. In addition, the assay
has been shown to work in murine cells and in a variety of human cancer cells.
Furthermore, the assay is suitable for detecting the DNA damage response induced
by treatment with temozolomide and methylmethane sulfonate (MMS). Lastly, the
assay has been shown to be robust over a period of several years.
PMID- 27610221
TI - Results of an attempt to reproduce the STAP phenomenon.
AB - In 2014, Obokata and colleagues reported their observation of a novel cell
reprogramming phenomenon they named 'stimulus-triggered acquisition of
pluripotency' (STAP). The most conclusive evidence for the pluripotency of so
called STAP cells was the purported ability of such cells to contribute to
chimera formation. Here, I report the results of an attempt by Haruko Obokata to
replicate the phenomenon under the supervision of the Scientific Validity
Examination Team of RIKEN. In this follow-up study, putative STAP cells prepared
by Haruko Obokata were injected into 1051 embryos, of which 591 were recovered.
However, the injected cells made no significant contribution in any tissue in any
of the embryos that developed.
PMID- 27610222
TI - High prevalence of diabetes mellitus and impaired glucose tolerance in liver
cancer patients: A hospital based study of 4610 patients with benign tumors or
specific cancers.
AB - OBJECTIVE: The prevalence of diabetes mellitus (DM), impaired glucose tolerance
(IGT) and impaired fasting glucose (IFG) were hypothesised to be different among
different tumor patients. This study aimed to study the association between the
prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer,
cervical cancer, nasopharyngeal cancer and benign tumor. METHODS: A hospital
based retrospective study was conducted on 4610 patients admitted to the Internal
Medical Department of the Affiliated Tumor Hospital of Guangxi Medical
University, China. Logistic regression was used to examine the association
between gender, age group, ethnicity , cancer types or benign tumors and
prevalence of DM, IFG, IGT. RESULTS: Among 4610 patients, there were 1000 liver
cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients,
230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign
tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7%
and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%,
respectively, in colorectal cancer patients, significantly higher than that of
benign cancers. After adjusting for gender, age group, and ethnicity, the
prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66)
and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively.
CONCLUSION: There was a high prevalence of DM and IGT in liver cancer patients.
PMID- 27610223
TI - Metagenomic analysis of an ecological wastewater treatment plant's microbial
communities and their potential to metabolize pharmaceuticals.
AB - Pharmaceuticals and other micropollutants have been detected in drinking water,
groundwater, surface water, and soil around the world. Even in locations where
wastewater treatment is required, they can be found in drinking water wells,
municipal water supplies, and agricultural soils. It is clear conventional
wastewater treatment technologies are not meeting the challenge of the mounting
pressures on global freshwater supplies. Cost-effective ecological wastewater
treatment technologies have been developed in response. To determine whether the
removal of micropollutants in ecological wastewater treatment plants (WWTPs) is
promoted by the plant-microbe interactions, as has been reported for other
recalcitrant xenobiotics, biofilm microbial communities growing on the surfaces
of plant roots were profiled by whole metagenome sequencing and compared to the
microbial communities residing in the wastewater. In this study, the
concentrations of pharmaceuticals and personal care products (PPCPs) were
quantified in each treatment tank of the ecological WWTP treating human
wastewater at a highway rest stop and visitor center in Vermont. The
concentrations of detected PPCPs were substantially greater than values reported
for conventional WWTPs likely due to onsite recirculation of wastewater. The
greatest reductions in PPCPs concentrations were observed in the anoxic treatment
tank where Bacilli dominated the biofilm community. Benzoate degradation was the
most abundant xenobiotic metabolic category identified throughout the system.
Collectively, the microbial communities residing in the wastewater were
taxonomically and metabolically more diverse than the immersed plant root
biofilm. However, greater heterogeneity and higher relative abundances of
xenobiotic metabolism genes was observed for the root biofilm.
PMID- 27610224
TI - Recent advances in understanding multiple myeloma.
AB - There have been major recent advancements in the understanding and management of
multiple myeloma. Diagnostic criteria have been revised and former ultra-high
risk smoldering multiple myeloma is now considered multiple myeloma in need of
treatment. Understanding clonal progression, evolution, and tides not only has
helped elucidate the disease behavior but might help expand therapeutic choices
in order to select appropriate treatment for patients. Unprecedented response
rates with modern triplet induction therapies containing proteasome inhibitor and
immunomodulators have made this approach standard for initial treatment. The US
Food and Drug Administration approved four new drugs (two targeted antibodies and
two oral agents) in 2015 in relapsed/refractory multiple myeloma and these drugs
along with the other already-available drugs have now increased the choices of
regimens. Even drugs without single-agent activity, such as panobinostat and
elotuzumab, have an important role, especially in the proteasome inhibitor
refractory setting. Recent studies done in the context of novel agent induction
suggest that high-dose therapy followed by autologous transplant continues to
improve response rates and progression-free survival, thus underscoring their
role in transplant-eligible patients. Evolving paradigms in the treatment of
multiple myeloma include newer promising immune approaches, such as adoptive
cellular therapies, vaccines, or antibody-based immune manipulations. Though
multiple myeloma is still considered incurable, it is clear that with the
improved understanding of disease biology and clonal architecture of relapse
combined with the availability of multi-targeted approaches, we are ever closer
to a lasting cure or transformation into indolent and long-lasting disease
courses or both.
PMID- 27610225
TI - Advances in understanding itching and scratching: a new era of targeted
treatments.
AB - Chronic itch is a significant health burden with few effective treatments. As
such, itch researchers seek to understand the mechanisms behind itch and to find
potential targets for treatment. The field of itch research is dynamic, and many
advances have been made so far this decade. In particular, major steps forward
include the identification of new peripheral and central itch mediators and
modulators, the discovery of greater roles for immune cells and glia in itch
transmission, and a focus on the brain processing of itching and scratching.
Finally, several new therapeutic interventions for itch have shown success in
clinical trials.
PMID- 27610226
TI - Recent advances in understanding and managing asthma.
AB - This review highlights the important articles published in the area of asthma
research from January 2015 to July 2016. In basic science, significant advances
have been made in understanding the link between the innate immune response and
type II acquired immune responses in asthma and the role of the airway
epithelium. Novel information continues to emerge with regard to the pathogenesis
and heterogeneity of severe asthma. There have been important translational
clinical trials in the areas of childhood asthma, treatment of allergy to improve
asthma outcomes, and improving drug delivery to optimize the management of
asthma. In addition, there are increasing data concerning the application of
biological agents to the management of severe asthma. This body of work discusses
the most notable advances in the understanding and management of asthma.
PMID- 27610227
TI - The rise and fall of infectious disease in a warmer world.
AB - Now-outdated estimates proposed that climate change should have increased the
number of people at risk of malaria, yet malaria and several other infectious
diseases have declined. Although some diseases have increased as the climate has
warmed, evidence for widespread climate-driven disease expansion has not
materialized, despite increased research attention. Biological responses to
warming depend on the non-linear relationships between physiological performance
and temperature, called the thermal response curve. This leads performance to
rise and fall with temperature. Under climate change, host species and their
associated parasites face extinction if they cannot either thermoregulate or
adapt by shifting phenology or geographic range. Climate change might also affect
disease transmission through increases or decreases in host susceptibility and
infective stage (and vector) production, longevity, and pathology. Many other
factors drive disease transmission, especially economics, and some change in time
along with temperature, making it hard to distinguish whether temperature drives
disease or just correlates with disease drivers. Although it is difficult to
predict how climate change will affect infectious disease, an ecological approach
can help meet the challenge.
PMID- 27610228
TI - Herpes simplex virus and the lexicon of latency and reactivation: a call for
defining terms and building an integrated collective framework.
AB - The field of herpes simplex virus (HSV) latency and reactivation has been marked
by controversy, which is not unexpected considering the complexities of the
biology involved. While controversy is an important tool for digging to the
bottom of difficult issues, we propose that unproductive conflict in the field
arises in part from poorly defined terminology and the need for a collective
framework. The uses of advanced global molecular and next-generation sequencing
approaches and an increasing array of in vitro model systems have provided new
molecular-level insights into HSV latency and reactivation, with the promise of
expanding our concepts of these processes. However, our current framework and
language are inadequate to effectively integrate new data streams into the
established theories. In this brief perspective, we look back into the past to
examine when and how the lexicon of HSV latency and reactivation arose in the
literature and its evolution. We propose to open a dialogue among investigators
for the purpose of updating and clearly defining terms used to describe these
processes and to build a collective integrated framework to move our field
forward.
PMID- 27610230
TI - GplusE: beyond genomic selection.
AB - GplusE is a strategy for genomic selection in which the accuracy of assessment in
the reference population for a primary trait such as yield is increased by the
incorporation of data from high- throughput field phenotyping platforms. This
increase in precision comes from both exploiting genetic relationships between
traits and reducing the effect of environmental influences upon them. We describe
a collaborative project among researchers and breeders to develop a large
reference population of elite UK wheat lines. This will be used to test the
method, to study the design of the reference population, and to test genotyping
strategies and imputation methods. Finally, it will provide data to pump-prime
the application of genomic selection to UK winter wheat breeding.
PMID- 27610231
TI - Alternate wetting and drying irrigation maintained rice yields despite half the
irrigation volume, but is currently unlikely to be adopted by smallholder lowland
rice farmers in Nepal.
AB - Alternate wetting and drying (AWD) irrigation can save water while maintaining
rice yields, but in some countries its adoption by farmers remains limited. Key
knowledge gaps include the effect of AWD on early vegetative vigor and its
relationship with yield; the effects of AWD on yield and water use efficiency of
local cultivars used by smallholder farmers; and the socio-economic factors
influencing current irrigation scheduling. To address these questions, an on-farm
field trial of dry-season (chaite) rice, comparing two locally important
cultivars (Hardinath-1 and CH-45) under AWD imposed from 1 week after
transplanting to flowering and continuous flooding (CF), was carried out in
Agyauli in the central Terai region of Nepal, and triangulated with social
research methods exploring the rationale for current irrigation scheduling and
perceptions of AWD. Although AWD plots received on average 57% less irrigation
water than CF plots, yields did not significantly differ between irrigation
treatments, indicating that AWD could considerably enhance crop water use
efficiency in this region. In the earlier flowering, more vigorous CH-45, there
were no treatment differences in any yield component while in the later flowering
Hardinath-1, an 11% decrease in filled grain number was compensated by a 14%
increase in the percentage of effective tillers per hill. Although leaf
elongation rate on the main tiller did not differ between treatments, tillering
and green fraction (a measure of canopy closure) were significantly higher under
AWD. Surveys established that most local farmers are already using a local
adaptation of AWD to modify irrigation volumes, in some cases in response to a
limited and unreliable water supply. However, farmers have few direct incentives
to reduce overall water use under current water governance, and formal AWD
practices are therefore unlikely to be adopted despite their viability as a water
saving irrigation technique.
PMID- 27610229
TI - Linking Alpha to Omega: diverse and dynamic RNA-based mechanisms to regulate gene
expression by 5'-to-3' communication.
AB - Communication between the 5' and 3' ends of a eukaryotic messenger RNA (mRNA) or
viral genomic RNA is a ubiquitous and important strategy used to regulate gene
expression. Although the canonical interaction between initiation factor proteins
at the 5' end of an mRNA and proteins bound to the polyadenylate tail at the 3'
end is well known, in fact there are many other strategies used in diverse ways.
These strategies can involve "non-canonical" proteins, RNA structures, and direct
RNA-RNA base-pairing between distal elements to achieve 5'-to-3' communication.
Likewise, the communication induced by these interactions influences a variety of
processes linked to the use and fate of the RNA that contains them. Recent
studies are revealing how dynamic these interactions are, possibly changing in
response to cellular conditions or to link various phases of the mRNA's life,
from translation to decay. Thus, 5'-to-3' communication is about more than just
making a closed circle; the RNA elements and associated proteins are key players
in controlling gene expression at the post-transcriptional level.
PMID- 27610233
TI - A new emphasis on root traits for perennial grass and legume varieties with
environmental and ecological benefits.
AB - Grasslands cover a significant proportion of the agricultural land within the UK
and across the EU, providing a relatively cheap source of feed for ruminants and
supporting the production of meat, wool and milk from grazing animals. Delivering
efficient animal production from grassland systems has traditionally been the
primary focus of grassland-based research. But there is increasing recognition of
the ecological and environmental benefits of these grassland systems and the
importance of the interaction between their component plants and a host of other
biological organisms in the soil and in adjoining habitats. Many of the
ecological and environmental benefits provided by grasslands emanate from the
interactions between the roots of plant species and the soil in which they grow.
We review current knowledge on the role of grassland ecosystems in delivering
ecological and environmental benefits. We will consider how improved grassland
can deliver these benefits, and the potential opportunities for plant breeding to
improve specific traits that will enhance these benefits whilst maintaining
forage production for livestock consumption. Opportunities for exploiting new
plant breeding approaches, including high throughput phenotyping, and for
introducing traits from closely related species are discussed.
PMID- 27610232
TI - The contribution of wheat to human diet and health.
AB - Wheat is the most important staple crop in temperate zones and is in increasing
demand in countries undergoing urbanization and industrialization. In addition to
being a major source of starch and energy, wheat also provides substantial
amounts of a number of components which are essential or beneficial for health,
notably protein, vitamins (notably B vitamins), dietary fiber, and
phytochemicals. Of these, wheat is a particularly important source of dietary
fiber, with bread alone providing 20% of the daily intake in the UK, and well
established relationships between the consumption of cereal dietary fiber and
reduced risk of cardio-vascular disease, type 2 diabetes, and forms of cancer
(notably colo-rectal cancer). Wheat shows high variability in the contents and
compositions of beneficial components, with some (including dietary fiber)
showing high heritability. Hence, plant breeders should be able to select for
enhanced health benefits in addition to increased crop yield.
PMID- 27610234
TI - Diversification and use of bioenergy to maintain future grasslands.
AB - Grassland agriculture is experiencing a number of threats including declining
profitability and loss of area to other land uses including expansion of the
built environment as well as from cropland and forestry. The use of grassland as
a natural resource either in terms of existing vegetation and land cover or
planting of new species for bioenergy and other nonfood applications presents an
opportunity, and potential solution, to maintain the broader ecosystem services
that perennial grasslands provide as well as to improve the options for grassland
farmers and their communities. This paper brings together different grass or
grassland-based studies and considers them as part of a continuum of strategies
that, when also combined with improvements in grassland production systems, will
improve the overall efficiency of grasslands as an important natural resource and
enable a greater area to be managed, replanted or conserved. These
diversification options relate to those most likely to be available to farmers
and land owners in the marginally economic or uneconomic grasslands of middle to
northern Europe and specifically in the UK. Grasslands represent the predominant
global land use and so these strategies are likely to be relevant to other areas
although the grass species used may vary. The options covered include the use of
biomass derived from the management of grasses in the urban and semi urban
environment, semi-natural grassland systems as part of ecosystem management,
pasture in addition to livestock production, and the planting and cropping of
dedicated energy grasses. The adoption of such approaches would not only increase
income from economically marginal grasslands, but would also mitigate greenhouse
gas emissions from livestock production and help fund conservation of these
valuable grassland ecosystems and landscapes, which is increasingly becoming a
challenge.
PMID- 27610235
TI - The association between Korean workers' presenteeism and psychosocial factors
within workplaces.
AB - BACKGROUND: Presenteeism, a concept that has recently undergone active study, is
the act of attending work while sick. This study investigates the association
between presenteeism and various psychosocial factors within workplaces. METHODS:
This study analyzed 29246 wage earners from the third Korean Working Conditions
Survey (KWCS, 2011) data using the logistic regression analysis to investigate
the association between presenteeism and various psychosocial factors within
workplaces. RESULTS: Among the 29246 wage earners, 6347 (21.7 %) showed
presenteeism. Those who experienced age discrimination at work (adjusted odds
ratio (aOR) 1.77: 95 % CI 1.56-2.00), educational background discrimination (aOR
1.35: 95 % CI 1.22-1.51), regional discrimination (aOR 1.55: 95 % CI 1.31-1.83),
sexual discrimination (aOR 1.65: 95 % CI 1.41-1.94), employment type
discrimination (aOR 2.13: 95 % CI 1.89-2.40), physical violence (aOR 1.92: 95 %
CI 1.45-2.55), sexual harassment (aOR 2.90: 95 % CI 2.01-4.19), job insecurity
(aOR 1.36: 95 % CI 1.18-1.56), work-life imbalance (aOR 1.38: 95 % CI 1.29-1.47),
low job satisfaction (aOR 2.04: 95 % CI 1.91-2.17), no colleague support (aOR
1.11: 95 % CI 1.02-1.21), job stress (aOR 1.89: 95 % CI 1.76-2.02), emotional
labor (aOR 1.50: 95 % CI 1.41-1.60), high work intensity (aOR 1.31: 95 % CI 1.23
1.38), and 3 groups of job strain that are passive group (aOR 1.09: 95 % CI 1.00
1.18), active group (aOR 1.39: 95 % CI 1.28-1.51), and high strain group (aOR
1.35: 95 % CI 1.24-1.46) showed an increased risk of presenteeism compared to
their respective counterparts (p < 0.01). CONCLUSIONS: The study results
confirmed the association between presenteeism and various psychosocial factors
within workplaces. Considering that presenteeism negatively affects productivity
and the mental and physical health of individuals, managing various psychosocial
factors within workplaces is proposed to reduce presenteeism.
PMID- 27610236
TI - Health care strategy for ensuring work ability in an aging Korea.
AB - The rapid aging trend in South Korea will cause a growing shortage of labor and
decreasing quality of the labor force. The purpose of this commentary is to
recommend a health care strategy to maintain and promote the work ability of
employees in an aging Korea. Strategies to promote the work ability require the
collaboration of governmental agencies at the central and local levels. First,
the common goal should be the reinforcement of follow-up measure in general
medical examinations and the promotion of healthy lifestyles for workers. Second,
collaborating activities should be performed among the Worker's Health Center,
the Health Promotion Center, and community health centers. In conclusion, health
care strategies for ensuring the work ability in an aging Korea require the
collaboration of governmental agencies at the central and local levels.
PMID- 27610237
TI - Transcriptome analyses of the Dof-like gene family in grapevine reveal its
involvement in berry, flower and seed development.
AB - The Dof (DNA-binding with one finger) protein family spans a group of plant
transcription factors involved in the regulation of several functions, such as
plant responses to stress, hormones and light, phytochrome signaling and seed
germination. Here we describe the Dof-like gene family in grapevine (Vitis
vinifera L.), which consists of 25 genes coding for Dof. An extensive in silico
characterization of the VviDofL gene family was performed. Additionally, the
expression of the entire gene family was assessed in 54 grapevine tissues and
organs using an integrated approach with microarray (cv Corvina) and real-time
PCR (cv Pinot Noir) analyses. The phylogenetic analysis comparing grapevine
sequences with those of Arabidopsis, tomato, poplar and already described Dof
genes in other species allowed us to identify several duplicated genes. The
diversification of grapevine DofL genes during evolution likely resulted in a
broader range of biological roles. Furthermore, distinct expression patterns were
identified between samples analyzed, corroborating such hypothesis. Our
expression results indicate that several VviDofL genes perform their functional
roles mainly during flower, berry and seed development, highlighting their
importance for grapevine growth and production. The identification of similar
expression profiles between both approaches strongly suggests that these genes
have important regulatory roles that are evolutionally conserved between
grapevine cvs Corvina and Pinot Noir.
PMID- 27610238
TI - Mental health care in post-genocide Rwanda: evaluation of a program specializing
in posttraumatic stress disorder and substance abuse.
AB - BACKGROUND: Following the genocide, millions of Rwandans are likely living with
posttraumatic stress disorder (PTSD). Le Centre Psychotherapeutique Icyizere
provides the only specialized treatment for PTSD in the Rwandan healthcare
system. METHODS: Demographics, diagnosis, treatment, outcomes, and scores on
assessments of functioning and PTSD were recorded from clinical charts of all
patients receiving care between October 2013 and 2014. Descriptive statistics and
within-group t tests comparing functional impairment and PTSD symptoms at intake
to discharge and follow-up were calculated. RESULTS: A total of 719 patients
(55.08% male) received care. Patients were more educated, more likely to live in
the capital, and less likely to be married than the general population. Patients
reported high desire for, and strong satisfaction with, care. Most patients
(55.60%) were still in care by the end of the program evaluation. Functioning
improved from intake to discharge (p < 0.001), and improvements were sustained at
follow-up (p < 0.001). Most adults were diagnosed with psychotic disorders,
substance use disorders, or depression. Only 20 patients were diagnosed with
PTSD, and symptoms were improved at discharge (p = 0.003). CONCLUSIONS: This
program evaluation demonstrated the utility of a low-resource information
management system to provide clarity about the patient population and outcomes.
Results suggest that services are effective and sustainable, although people with
PTSD were not the primary recipients of care. Disparities in care by diagnosis,
education, marital status, and geography are discussed. Results have contributed
to changes in service delivery and care and efforts to increase access to care.
PMID- 27610239
TI - Protocol for meta-analysis of temperature reduction in animal models of cardiac
arrest.
AB - Targeted temperature management (TTM) of 32-34 degrees C has been the standard
treatment for out-of-hospital cardiac arrest since clinical trials in 2002 showed
benefits to survival and neurological outcome. Recently, this treatment has been
challenged by another clinical trial showing no difference in outcome between TTM
of 33 degrees C and 36 degrees C. This protocol describes the methodology for a
meta-analysis detailing temperature-reducing interventions to treat global
ischaemia in animal models. By combining relevant data sets in the literature, we
will explore the experimental evidence for TTM. Our aims are to explain possible
translational gaps and provide methodological considerations for future
experimental research and clinical trials.
PMID- 27610241
TI - Corrigendum to "Expression of HGF and c-Met Proteins in Human Keratoconus
Corneas".
AB - [This corrects the article DOI: 10.1155/2015/852986.].
PMID- 27610240
TI - Palaeospondylus as a primitive hagfish.
AB - BACKGROUND: The taxonomic position of the Middle Devonian fish-like animal
Palaeospondylus has remained enigmatic, due mainly to the inability to identify
homologous cranial elements. This animal has been classified into nearly all of
the major vertebrate taxa over a century of heuristic taxonomic research, despite
the lack of conclusive morphological evidence. RESULTS: Here we report the first
comparative morphological analysis of hagfish embryos and Palaeospondylus, and a
hitherto overlooked resemblance in the chondrocranial elements of these animals;
i.e., congruence in the arrangement of the nasal capsule, neurocranium and
mandibular arch-derived velar bar. The large ventral skeletal complex of
Palaeospondylus is identified as a cyclostome-specific lingual apparatus.
Importantly, the overall morphological pattern of the Palaeospondylus cranium
coincides well with the cyclostome pattern of craniofacial development, which is
not shared with that of crown gnathostomes. Previously, the presence of the
vertebral column in Palaeospondylus made its assignment problematic, but the
recent identification of this vertebral element in hagfish is consistent with an
affinity between this group and Palaeospondylus. CONCLUSION: These lines of
evidence support the hagfish affinity of Palaeospondylus. Moreover, based on the
less specialized features in its cranial morphology, we conclude that
Palaeospondylus is likely a stem hagfish.
PMID- 27610242
TI - Intrastromal Injection of Bevacizumab in the Management of Corneal
Neovascularization: About 25 Eyes.
AB - Introduction. Corneal neovessels are a major risk factor for corneal graft
rejection, due to the loss of the immune privilege. The purpose of this study is
to evaluate the effectiveness of intrastromal injection of bevacizumab in the
treatment of corneal neovascularization. Material and Methods. This is a
prospective study that included 25 eyes of 22 patients with deep corneal
neovessels, treated with intrastromal injections of bevacizumab. Results. The
average age of patients was 31 years ranging from 16 to 44 years. The causes of
neovascularization were dominated by herpetic keratitis (10 cases). The evolution
was marked by complete regress of neovessels in 16 patients, partial regress in 6
cases, and reduced opacity and improved visual acuity in 5 patients. No side
effects were noted. Discussion. Short-term results demonstrated the effectiveness
of intrastromal injection of bevacizumab in the treatment of corneal neovessels.
It may be an option or a complement to other useful treatments in stabilizing or
improving vision. Conclusion. Bevacizumab is an effective additional treatment
for the improvement of corneal transplants prognosis with preoperative corneal
neovascularization.
PMID- 27610243
TI - Feasibility and Acceptability of a Smartphone App for Daily Reports of Substance
Use and Antiretroviral Therapy Adherence among HIV-Infected Adults.
AB - While substance use is one of the most consistent predictors of poor adherence to
antiretroviral therapy (ART), few studies among people living with HIV (PLH) have
utilized mobile phone-based assessment of these health behaviors. PLH were
recruited from primary care clinics to report ART and substance use using a
smartphone application (app) for 14 consecutive days. The app's feasibility as a
data collection tool was evaluated quantitatively via surveys and qualitatively
via in-depth interviews to assess daily report completion, compliance, and study
satisfaction. Overall, 26 participants (M = 49.5 years, 76% male) completed 95.3%
of time-based daily reports. Participants reported high satisfaction with the app
and expressed future interest in using smartphones to report daily behaviors.
High completion rates and participant acceptability suggest that smartphones are
a feasible, acceptable method for collecting substance use and ART data among
PLH. Potential areas of concern such as sufficient training and assistance for
those with limited smartphone experience should be considered for future app
based research studies among PLH.
PMID- 27610244
TI - The Disruption of Geniculocalcarine Tract in Occipital Neoplasm: A Diffusion
Tensor Imaging Study.
AB - Aim. Investigate the disruption of geniculocalcarine tract (GCT) in different
occipital neoplasm by diffusion tensor imaging (DTI). Methods. Thirty-two
subjects (44.1 +/- 3.6 years) who had single occipital neoplasm (9 gliomas, 6
meningiomas, and 17 metastatic tumors) with ipsilateral GCT involved and thirty
healthy subjects (39.2 +/- 3.3 years) underwent conventional sequences scanning
and diffusion tensor imaging by a 1.5T MR scanner. The diffusion-sensitive
gradient direction is 13. Compare the fractional anisotropy (FA) and mean
diffusivity (MD) values of healthy GCT with the corresponding values of GCT in
peritumoral edema area. Perform diffusion tensor tractography (DTT) on GCT by the
line propagation technique in all subjects. Results. The FA values of GCT in
peritumoral edema area decreased (P = 0.001) while the MD values increased (P =
0.002) when compared with healthy subjects. There was no difference in the FA
values across tumor types (P = 0.114) while the MD values of GCT in the
metastatic tumor group were higher than the other groups (P = 0.001). GCTs were
infiltrated in all the 9 gliomas cases, with displacement in 2 cases and
disruption in 7 cases. GCTs were displaced in 6 meningiomas cases. GCTs were
displaced in all the 7 metastatic cases, with disruption in 7 cases. Conclusions.
DTI represents valid markers for evaluating GCT's disruption in occipital
neoplasm. The disruption of GCT varies according to the properties of neoplasm.
PMID- 27610245
TI - The Effect of the More Active MuMs in Stirling Trial on Body Composition and
Psychological Well-Being among Postnatal Women.
AB - Introduction. Physical activity is important for health and well-being; however,
rates of postnatal physical activity can be low. This paper reports the secondary
outcomes of a trial aimed at increasing physical activity among postnatal women.
Methods. More Active MuMs in Stirling (MAMMiS) was a randomised controlled trial
testing the effect of physical activity consultation and pram walking group
intervention among inactive postnatal women. Data were collected on postnatal
weight, body composition, general well-being, and fatigue. Participants were also
interviewed regarding motivations and perceived benefits of participating in the
trial. Results. There was no significant effect of the intervention on any
weight/body composition outcome or on general well-being at three or six months
of follow-up. There was a significant but inconsistent difference in fatigue
between groups. Qualitative data highlighted a number of perceived benefits to
weight, body composition, and particularly well-being (including improved
fatigue) which were not borne out by objective data. Discussion. The MAMMiS study
found no impact of the physical activity intervention on body composition and
psychological well-being and indicates that further research is required to
identify successful approaches to increase physical activity and improve health
and well-being among postnatal women.
PMID- 27610246
TI - Addressing Work-Related Issues in Medical Rehabilitation: Revision of an Online
Information Tool for Healthcare Professionals.
AB - Background. Medical rehabilitation increasingly considers occupational issues as
determinants of health and work ability. Information on work-related
rehabilitation concepts should therefore be made available to healthcare
professionals. Objective. To revise a website providing healthcare professionals
in medical rehabilitation facilities with information on work-related concepts in
terms of updating existing information and including new topics, based on
recommendations from implementation research. Method. The modification process
included a questionnaire survey of medical rehabilitation centers (n = 28); two
workshops with experts from rehabilitation centers, health payers, and research
institutions (n = 14); the selection of new topics and revision of existing text
modules based on expert consensus; and an update of good practice descriptions of
work-related measures. Results. Health payers' requirements, workplace
descriptions, and practical implementation aids were added as new topics. The
database of good practice examples was extended to 63 descriptions. Information
on introductory concepts was rewritten and supplemented by current data.
Diagnostic tools were updated by including additional assessments. Conclusions.
Recommendations from implementation research such as assessing user needs and
including expert knowledge may serve as a useful starting point for the
dissemination of information on work-related medical rehabilitation into
practice. Web-based information tools such as the website presented here can be
quickly adapted to current evidence and changes in medicolegal regulations.
PMID- 27610247
TI - Design, Characterization, and Optimization of Controlled Drug Delivery System
Containing Antibiotic Drug/s.
AB - The objective of this work was design, characterization, and optimization of
controlled drug delivery system containing antibiotic drug/s. Osmotic drug
delivery system was chosen as controlled drug delivery system. The porous osmotic
pump tablets were designed using Plackett-Burman and Box-Behnken factorial design
to find out the best formulation. For screening of three categories of polymers,
six independent variables were chosen for Plackett-Burman design. Osmotic agent
sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl
sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate
were chosen as independent variables. Optimization of osmotic tablets was done by
Box-Behnken design by selecting three independent variables. Osmotic agent sodium
chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose
acetate were chosen as independent variables. The result of Plackett-Burman and
Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former
had significant effect on the drug release up to 12 hr. The observed independent
variables were found to be very close to predicted values of most satisfactory
formulation which demonstrates the feasibility of the optimization procedure in
successful development of porous osmotic pump tablets containing antibiotic
drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as
key excipients.
PMID- 27610249
TI - Severe Bioprosthetic Mitral Valve Stenosis and Heart Failure in a Young Woman
with Systemic Lupus Erythematosus.
AB - A 23-year-old African American woman with a past medical history of systemic
lupus erythematous (SLE), secondary hypertension, and end stage renal disease
(ESRD) on hemodialysis for eight years was stable until she developed symptomatic
severe mitral regurgitation with preserved ejection fraction. She underwent a
bioprosthetic mitral valve replacement (MVR) at outside hospital. However, within
a year of her surgery, she presented to our hospital with NYHA class IV symptoms.
She was treated for heart failure but in view of her persistent symptoms and low
EF was considered for heart and kidney transplant. This was a challenge in view
of her history of lupus. We presumed that her stenosis of bioprosthetic valve was
secondary to lupus and renal disease. We hypothesized that her low ejection
fraction was secondary to mitral stenosis and potentially reversible. We
performed a dobutamine stress echocardiogram, which revealed an improved ejection
fraction to more than 50% and confirmed preserved inotropic contractile reserve
of her myocardium. Based on this finding, she underwent a metallic mitral valve
and tricuspid valve replacement. Following surgery, her symptoms completely
resolved. This case highlights the pathophysiology of lupus causing stenosis of
prosthetic valves and low ejection cardiomyopathy.
PMID- 27610250
TI - Platypnea-Orthodeoxia Syndrome after Transcatheter Aortic Valve Implantation.
AB - Progressive dyspnea and hypoxaemia in the subacute phase after transcatheter
aortic valve implantation (TAVI) are uncommon and warrant immediate assessment of
valve and prosthesis leaflet function to exclude thrombosis, as well as
investigation for other causes related to the procedure, such as left ventricular
dysfunction, pulmonary embolism, and respiratory sepsis. In this case, we report
the observation of a patient presenting two weeks after TAVI with arterial
hypoxaemia in an upright position, relieved by lying flat, and coupled with an
intracardiac shunt detected on echocardiography in the absence of pulmonary
hypertension, raising the suspicion of Platypnea-Orthodeoxia Syndrome (POS).
Invasive intracardiac haemodynamic assessment showed a significant right-to-left
shunt (Qp/Qs = 0.74), which confirmed the diagnosis, with subsequent closure of
the intracardiac defect resulting in immediate relief of symptoms and hypoxaemia.
To our knowledge, this is the first reported case of an interatrial defect and
shunt causing Platypnea-Orthodeoxia Syndrome after transcatheter aortic valve
implantation, resolved by percutaneous device closure.
PMID- 27610248
TI - Neuromuscular Plasticity: Disentangling Stable and Variable Motor Maps in the
Human Sensorimotor Cortex.
AB - Motor maps acquired with transcranial magnetic stimulation (TMS) are evolving as
a biomarker for monitoring disease progression or the effects of therapeutic
interventions. High test-retest reliability of this technique for long
observation periods is therefore required to differentiate daily or weekly
fluctuations from stable plastic reorganization of corticospinal connectivity. In
this study, a novel projection, interpolation, and coregistration technique,
which considers the individual gyral anatomy, was applied in healthy subjects for
biweekly acquired TMS motor maps over a period of twelve weeks. The intraclass
correlation coefficient revealed long-term reliability of motor maps with
relevant interhemispheric differences. The sensorimotor cortex and nonprimary
motor areas of the dominant hemisphere showed more extended and more stable
corticospinal connectivity. Long-term correlations of the MEP amplitudes at each
stimulation site revealed mosaic-like clusters of consistent corticospinal
excitability. The resting motor threshold, centre of gravity, and mean MEPs
across all TMS sites, as highly reliable cortical map parameters, could be
disentangled from more variable parameters such as MEP area and volume. Cortical
TMS motor maps provide high test-retest reliability for long-term monitoring when
analyzed with refined techniques. They may guide restorative interventions which
target dormant corticospinal connectivity for neurorehabilitation.
PMID- 27610251
TI - Ring Chromosome 4 in a Child with Multiple Congenital Abnormalities: A Case
Report and Review of the Literature.
AB - A female child born preterm with intrauterine growth retardation and presenting
with facial dysmorphism with clefts, microcephaly, limb deformities, and
congenital abnormalities involving cardiovascular and urinary systems is
described. Chromosomal analysis showed a de novo 46,XX,r(4)(p15.3q35) karyotype.
The clinical features of the patient were compared with the phenotypic
characteristics of 17 previously reported cases with ring chromosome 4 and those
with Wolf-Hirschhorn syndrome (4p-). Clinical features observed in this case are
consistent with the consensus phenotype in ring chromosome 4. Patent ductus
arteriosus and bilateral talipes equinovarus observed in this baby widen the
phenotypic spectrum associated with ring chromosome 4.
PMID- 27610252
TI - Acute Monocytic Leukemia Masquerading Behcet's Disease-Like Illness at Onset in
an Elderly Female.
AB - A previously healthy 74-year-old Japanese female was hospitalized with fever and
high C-reactive protein. She developed palatal herpangina-like aphthous ulcers,
localized intestinal wall thickening, terminal ileum ulcers, and an erythematous
acneiform rash; thus Behcet's disease-like illness was suspected. Significant
peripheral blood acute monocytosis developed during her hospitalization and acute
monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By
immunostaining, the infiltrating cells in the skin and the terminal ileum were
identified as monocytic leukemic cells. This case exhibited a unique initial
presentation of Behcet's disease-like illness associated with acute monocytic
leukemia.
PMID- 27610253
TI - Plesiomonas shigelloides Septic Shock Leading to Death of Postsplenectomy Patient
with Pyruvate Kinase Deficiency and Hemochromatosis.
AB - Although Plesiomonas shigelloides, a water-borne bacterium of the
Enterobacteriaceae family, usually causes self-limiting gastroenteritis with
diarrhea, several cases of sepsis have been reported. We report the case of a 43
year-old male patient with hemochromatosis, pyruvate kinase deficiency, and
asplenia via splenectomy who developed septic shock caused by P. shigelloides
complicated by respiratory failure, renal failure, liver failure, and
disseminated intravascular coagulation. Early aggressive antimicrobial therapy
and resuscitation measures were unsuccessful and the patient passed away. We
kindly suggest clinicians to implement early diagnosis of septic shock, empirical
coverage with antibiotics, and prompt volume resuscitation based on the high
mortality rate of P. shigelloides bacteremia.
PMID- 27610255
TI - Colon Adenoma Implicating Myasthenia Gravis: A Case Report of a Patient with
Postcolectomy Complications.
AB - We report the case of a 63-year-old patient with myasthenia gravis (MG) due to
acetylcholine receptor antibodies (AChR) who underwent colectomy due to colon
adenoma and developed myasthenic crisis and anastomosis leakage after surgery.
The patient underwent two plasma exchanges, 4 and 6 days preoperatively, and
received intravenous prednisolone and immunoglobulin infusion due to the crisis,
which included primarily bulbar symptoms. The patient developed on the 10th
postoperative day bowel obstruction symptoms and anastomosis leakage which
required surgical repair and ileostomy. Bowel obstruction occurred in a patient
with AChR related myasthenia after plasma exchange and during immunosuppression
although it is more commonly reported in patients with thymoma related
myasthenia.
PMID- 27610254
TI - Adult Primary Spinal Epidural Extraosseous Ewing's Sarcoma: A Case Report and
Review of the Literature.
AB - Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare
malignancy, especially in adults. Case Presentation. A 40-year-old male presented
with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass
with no osseous involvement. He underwent surgery for gross total resection of
the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated
with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of
the literature indicated only 45 previously reported cases of spinal epidural
extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma
in the spinal epidural space is a rare clinical entity that should be included in
the differential for spinal epidural masses. Its treatment is multidisciplinary
but frequently requires surgical intervention due to compressive neurologic
symptoms. Gross total resection appears to correlate with improved outcomes.
PMID- 27610256
TI - Extreme Elevation of Alkaline Phosphatase in a Pregnancy Complicated by
Gestational Diabetes and Infant with Neonatal Alloimmune Thrombocytopenia.
AB - There have been few case reports of isolated elevation of alkaline phosphatase
beyond the normal physiologic amount with subsequent return to baseline after
delivery. Here we present a similar case of extreme elevation of alkaline
phosphatase in a pregnancy complicated by gestational diabetes and subsequently
by neonatal alloimmune thrombocytopenia (NAIT).
PMID- 27610257
TI - A Gel Formulation Containing a New Recombinant Form of Manganese Superoxide
Dismutase: A Clinical Experience Based on Compassionate Use-Safety of a Case
Report.
AB - Background. We report a case of bilateral posterior subcapsular cataracts (PSCs)
in a 24-year-old man with an allergic conjunctivitis history caused by a long
term therapy with glucocorticoids. Case Presentation. The patient showed a visual
acuity of 9/10 for both eyes. He followed a therapy with ketotifen and bilastine
for four years. During the last six months before our evaluation, he was treated
with chloramphenicol and betamethasone, interrupted for onset of cataracts and
increased intraocular pressure. We treated him with ophthalmic gel preparation
containing a new recombinant form of manganese superoxide dismutase (rMnSOD) at a
concentration of 12.5 MUg/mL, only for the right eye, while left eye was treated
with standard protocol of Bendazac-lysine g 0.5. Conclusion. This case report
shows the protective effects of rMnSOD versus PSC disease, probably due to the
capacity of rMnSOD of countering free radical species.
PMID- 27610258
TI - Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a
Comprehensive Review of a Rare Entity.
AB - Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from
cells derived from the neural crest with neuroendocrine differentiation. Despite
the differences in the site of origin, nomenclature, biological behavior, and
functional status, NETs share certain ultrastructural and immunohistochemical
features. NETs are relative rare tumors with an annual incidence of 5.76 new
cases per 100.000 inhabitants and they usually appear in the gastrointestinal
tract or in the pulmonary system. Head and neck NETs are uncommon with limited
information regarding frequency, most of them showing small cell carcinoma
features. NETs that arise from the salivary glands are exceedingly rare.
Regardless of their low frequency, it is imperative to accurately differentiate
these tumors from the much more common squamous cell carcinomas and from
metastasis from another primary tumor due to the completely different therapeutic
approaches and prognosis. The diagnosis is based on the recognition of the
typical neuroendocrine architecture and immunohistochemical staining and on an
exhaustive work-up. Hereby, we report a case of a moderately differentiated NET
of the parotid gland that was treated with a complete parotidectomy. We summarize
the clues that led to the final diagnosis and major strategies that were employed
to manage the patient. We also perform a comprehensive review of the scarce
available literature on this topic.
PMID- 27610259
TI - Unicystic Ameloblastoma with Mural Proliferation Managed by Conservative
Treatment.
AB - Unicystic ameloblastoma is a distinguishable entity of ameloblastomas,
characterized by slow growth and being relatively locally aggressive. Three
histological types are recognized according to the degree of ameloblastomatous
epithelial extension, namely, luminal, intraluminal, and mural types. This
classification has a direct bearing on their biological behavior, treatment, and
prognosis. However, there is difficulty in determining the most appropriate form
of treatment for unicystic ameloblastoma. We present a case of unicystic
ameloblastoma that occurred in the right posterior mandible of 19-year-old girl,
which was enucleated and did not recur after 12-month follow-up.
PMID- 27610260
TI - Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge.
AB - Tuberculosis (TB) infection in pregnant women and newborn babies is always
challenging. Appropriate treatment is pivotal to curtail morbidity and mortality.
TB diagnosis or exposure to active TB can be emotionally distressing to the
mother. Circumstances can become more challenging for the physician if the
mother's TB status is unclear. Effective management of TB during pregnancy and
the postpartum period requires a multidisciplinary approach including
pulmonologist, obstetrician, neonatologist, infectious disease specialist, and TB
public health department. Current guidelines recommend primary Isoniazid
prophylaxis in TB exposed pregnant women who are immune-suppressed and have
chronic medical conditions or obstetric risk factors and close and sustained
contact with a patient with infectious TB. Treatment during pregnancy is the same
as for the general adult population. Infants born to mothers with active TB at
delivery should undergo a complete diagnostic evaluation. Primary Isoniazid
prophylaxis for at least twelve weeks is recommended for those with negative
diagnostic tests and no evidence of disease. Repeated negative diagnostic tests
are mandatory before interrupting prophylaxis. Separation of mother and infant is
only necessary when the mother has received treatment for less than 2 weeks, is
sputum smear-positive, or has drug-resistant TB. This case highlights important
aspects for management of TB during the postpartum period which has a higher
morbidity. We present a case of a young mother migrating from a developing nation
to the USA, who was found to have a positive quantiFERON test associated with
multiple cavitary lung lesions and gave birth to a healthy baby.
PMID- 27610261
TI - A Rare Case of Mixed Neuroendocrine Tumor and Adenocarcinoma of the Pancreas.
AB - Introduction. Neuroendocrine carcinoma (NEC) of pancreas is a rare tumor with
aggressive progression and poor prognosis. Its coexistence with adenocarcinoma
poses significant clinical problems and has not been addressed in the literature.
Methods. We describe a case of a 51-year-old male who underwent
pancreatoduodenectomy due to pancreatic head tumor 1.5 * 1 * 1.4 cm. Histological
examination of the specimen revealed a mixed neoplasm: (1) a well differentiated
adenocarcinoma, neoplastic blasts of which are extended focally to the submucosa
without invading the muscular layer, and (2) a low differentiated NEC consisting
of solid clusters and pagetoid formations. All 18 lymph nodes of the specimen
were free of neoplastic disease and the surgical margins of the specimen were
tumor-free. No adjuvant treatment was administered and two months after the
operation the patient developed liver metastasis. FNA cytology of the hepatic
lesions revealed low grade carcinoma with neuroendocrine characteristics. Five
lines of chemotherapy were administered: VP + CDDP, paclitaxel + ifosfamide +
Mesna + CDDP, Folfox + Avastin, Folfiri + Avastin, and CAV. During his treatment
he revealed PD and succumbed to his disease 13 months after the operation.
Conclusion. Coexistence of NEC with adenocarcinoma of the pancreas is a very rare
entity presenting significant challenges regarding its adjuvant treatment and the
treatment of distant relapse.
PMID- 27610262
TI - Squamous Cell Cancer Arising in an African American Male Cheek from Discoid
Lupus: A Rare Case and Review of the Literature.
AB - A 50-year-old African American male with Discoid Lupus Erythematosus (DLE)
presented to the dermatology clinic for a rapidly enlarging left cheek mass. The
mass failed to resolve with conservative measures. A biopsy revealed poorly
differentiated Squamous Cell Carcinoma (SCC). He was referred to Head and Neck
Surgery and successfully underwent a resection with free flap reconstruction.
Postoperatively he did well. Squamous cell skin carcinomas arising from lesions
of Discoid Lupus are rare and aggressive tumors with greater likelihood of
metastases. Cases have been reported among patients with different clinical
characteristics; we present a rare case arising in an African American male on
the face and involving the ear.
PMID- 27610263
TI - Severe Hypotension, Hypoxia, and Subcutaneous Erythema Induced by Indigo Carmine
Administration during Open Prostatectomy.
AB - Indigo carmine (also known as 5,5'-indigodisulfonic acid sodium salt or
indigotine) is a blue dye that is administered intravenously to examine the
urinary tract and usually is biologically safe and inert. Indigo carmine rarely
may cause adverse reactions. We treated a 66-year-old man who had general
anesthesia and radical retropubic prostatectomy for prostate cancer. He had a
previous history of allergy to bee sting with nausea, vomiting, and dizziness.
Within 1 minute after injection of indigo carmine for evaluation of the ureters,
the patient developed hypotension to 40 mmHg, severe hypoxia (the value of SpO2
(peripheral capillary oxygen saturation) was 75% on 40% inspired oxygen
concentration), poor air movement and bilateral diffuse wheezing on auscultation,
and marked subcutaneous erythema at the upper extremities. After treatment with
100% oxygen, epinephrine (total, 1.5 mg), hydrocortisone (100 mg),
diphenhydramine (50 mg), albuterol nebulizer (0.083%), and continuous infusion of
epinephrine (0.15 MUg/kg/min), the vital signs became stable, and he recovered
completely. In summary, indigo carmine rarely may cause life-threatening
anaphylactic or anaphylactoid reaction that may necessitate rapid treatment to
stabilize cardiovascular, hemodynamic, and pulmonary function.
PMID- 27610265
TI - The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in
Hospitalized Patients with Acute Respiratory Symptoms.
AB - Background. The clinical diagnosis of pneumonia is sometimes difficult since
chest radiographs are often indeterminate. In this study, we aimed to assess
whether serum C-reactive protein (CRP) could assist in identifying patients with
pneumonia. Methods. For one winter, all consecutive patients with acute
respiratory symptoms admitted to the emergency ward of a single center were
prospectively enrolled. In addition to chest radiographs, basic laboratory tests,
and microbiology, serum levels of CRP were measured at entry. Results. A total of
923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were
included. Subjects with a final diagnosis of pneumonia had higher serum CRP
levels (median 187 mg/L) than those with exacerbations of chronic obstructive
pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was
accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82-0.87).
The multilevel likelihood ratio (LR) for intervals of CRP provided useful
information on the posttest probability of having pneumonia. CRP intervals above
200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP
intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is
unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia
in hospitalized patients with acute respiratory symptoms.
PMID- 27610264
TI - Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to
Potential Clinical Application.
AB - Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops
slowly; however, there is no efficient method of early diagnosis, nor is there a
cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars
compacta and widespread aggregation of the alpha-synuclein protein (encoded by
the SNCA gene) in the form of Lewy bodies and Lewy neurites are the
neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone
gene duplications, triplications, and point mutations. However, the specific
mechanism of alpha-synuclein in Parkinson's disease remains obscure. Recent
research showed that various alpha-synuclein oligomers, pathological aggregation,
and propagation appear to be harmful in certain areas in Parkinson's disease
patients. This review summarizes our current knowledge of the pathogenetic
dysfunction of alpha-synuclein associated with Parkinson's disease and highlights
current approaches that seek to develop this protein as a possible diagnostic
biomarker and therapeutic target.
PMID- 27610266
TI - A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational
Context.
AB - The reliability of DrugWipe 5A on site test for principal drugs of abuse
(cannabis, amphetamines, cocaine, and opiates) detection in oral fluid was
assessed by comparing the on-site results with headspace solid-phase
microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS) analysis
on samples extracted by the device collection pad. Oral fluid samples were
collected at recreational settings (e.g., discos, pubs, and music bars) of Rome
metropolitan area. Eighty-three club goers underwent the on-site drug screening
test with one device. Independently from the result obtained, a second device was
used just to collect another oral fluid sample subsequently extracted and
analyzed in the laboratory following HS-SPME procedure, gas chromatographic
separation by a capillary column, and MS detection by electron impact ionization.
DrugWipe 5A on-site test showed 54 samples (65.1%) positive to one or more drugs
of abuse, whereas 75 samples (90.4%) tested positive for one or more substances
following GC-MS assay. Comparing the obtained results, the device showed
sensitivity, specificity, and accuracy around 80% for amphetamines class.
Sensitivity (67 and 50%) was obtained for cocaine and opiates, while both
sensitivity and accuracy were unsuccessful (29 and 53%, resp.) for cannabis,
underlying the limitation of the device for this latter drug class.
PMID- 27610267
TI - Isolation and Analysis of Phospholipids in Dairy Foods.
AB - The lipid fraction of milk is one of the most complex matrixes in foodstuffs due
to the presence of a high number of moieties with different physical and chemical
properties. Glycerolipids include glycerol and two fatty acids esterified in
positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than
in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base
linked to a fatty acid across an amide bond. Their amphiphilic nature makes them
suitable to be added into a variety of foods and recent investigations show that
phospholipids, mainly phosphatidylserine and sphingomyelin, can exert
antimicrobial, antiviral, and anticancer activities as well as positive effects
in Alzheimer's disease, stress, and memory decline. Polar lipids can be found as
natural constituents in the membranes of all living organisms with soybean and
eggs as the principal industrial sources, yet they have low contents in
phosphatidylserine and sphingomyelin. Animal products are rich sources of these
compounds but since there are legal restrictions to avoid transmission of prions,
milk and dairy products are gaining interest as alternative sources. This review
summarizes the analysis of polar lipids in dairy products including sample
preparation (extraction and fractionation/isolation) and analysis by GC or HPLC
and the latest research works using ELSD, CAD, and MS detectors.
PMID- 27610269
TI - Association of Visual Acuity and Cognitive Impairment in Older Individuals:
Fujiwara-kyo Eye Study.
AB - Both visual impairment and cognitive impairment are essential factors that
determine the quality of life in the aged population. The aim of this study was
to determine if a correlation existed between visual acuity and cognitive
impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a
cross-sectional study of individuals aged >=68 years who lived in Nara Prefecture
of Japan. Participants underwent ophthalmological examinations and cognitive
function test. A mild visual impairment was defined as having a best corrected
visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR)
units in the better eye. Cognitive impairment was defined as having a Mini-Mental
State Examination (MMSE) score of <=23 points. A total to 2818 individuals
completed the examinations. The mean age of the participants was 76.3 +/- 4.8
years (mean +/- standard deviation). The mean BCVA of the better eye was -0.02 +/
0.13 logMAR units and 6.6% subjects were classified as being mildly visually
impaired. The mean MMSE score was 27.3 +/- 2.3 and 5.7% subjects were classified
as being cognitively impaired. The proportion of subjects with cognitive or
moderate visual impairment increased with age, and there was a significant
correlation between the visual acuity and MMSE score (r = -0.10, p < 0.0001).
Subjects with mild visual impairments had 2.4 times higher odds of having
cognitive impairment than those without visual impairment (odds ratio 2.4, 95%
confidence interval, 1.5-3.8, p < 0.001) after adjusting for age, sex, and length
of education. We conclude that it may be important to maintain good visual acuity
to reduce the risk of having cognitive impairment.
PMID- 27610268
TI - Recent Applications of Coaxial and Emulsion Electrospinning Methods in the Field
of Tissue Engineering.
AB - Electrospinning has emerged as an effective method of producing nanoscale fibers
for use in multiple fields of study. One area of significant interest is
nanofiber utilization for tissue engineering because the nanofibrous mats can
mimic the native extracellular matrix of biological tissues. A logical next step
is the inclusion of certain molecules and compounds to accelerate or increase the
efficacy of tissue regeneration. Two methods are under scrutiny for their
capability to encapsulate therapeutic compounds within electrospun nanofibers:
emulsion and coaxial electrospinning. Both have advantages and disadvantages,
which need to be taken into careful consideration when deciding to use them in a
specific application. Several examples are provided here to highlight the vast
potential of multilayered nanofibers as well as the emergence of new techniques
to produce three-dimensional scaffolds of nanofibers for use in the field of
tissue engineering.
PMID- 27610270
TI - Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused
Three-Dimensional Multicompartment Bioreactor.
AB - The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds
great potential for application in regenerative medicine, pharmacological drug
screening, and toxicity testing. However, full maturation of hiPSC into
functional hepatocytes has not yet been achieved. In this study, we investigated
the potential of a dynamic three-dimensional (3D) hollow fiber membrane
bioreactor technology to improve the hepatic differentiation of hiPSC in
comparison to static two-dimensional (2D) cultures. A total of 100 * 10(6) hiPSC
were seeded into each 3D bioreactor (n = 3). Differentiation into definitive
endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the
culture medium. For further maturation, hepatocyte growth factor and oncostatin M
were added. The same differentiation protocol was applied to hiPSC maintained in
2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was
significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a
typical characteristic for mature hepatocytes, was higher after hepatic
differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple
cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in
both groups, although at a lower level compared to primary human hepatocytes
(PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors
compared with 2D cultures, which is in line with results from gene expression.
Immunofluorescence staining showed that the majority of cells was positive for
albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at
the end of the differentiation process. In addition, cytokeratin 19 (CK19)
staining revealed the formation of bile duct-like structures in 3D bioreactors
similar to native liver tissue. The results indicate a better maturation of hiPSC
in the 3D bioreactor system compared to 2D cultures and emphasize the potential
of dynamic 3D culture systems in stem cell differentiation approaches for
improved formation of differentiated tissue structures.
PMID- 27610271
TI - Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological
Sutures to an Infarcted Heart.
AB - Stem cell therapy has the potential to improve cardiac function after myocardial
infarction (MI); however, existing methods to deliver cells to the myocardium,
including intramyocardial injection, suffer from low engraftment rates. In this
study, we used a rat model of acute MI to assess the effects of human mesenchymal
stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week
after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded
hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged
to assess mechanical function in the infarct region. Regional parameters assessed
were regional stroke work (RSW) and systolic area of contraction (SAC) and global
parameters derived from the pressure waveform. MI (n = 6) significantly decreased
RSW (0.026 +/- 0.011) and SAC (0.022 +/- 0.015) when compared with sham operation
(RSW: 0.141 +/- 0.009; SAC: 0.166 +/- 0.005, n = 6) (p < 0.05). The delivery of
unseeded biological sutures to the infarcted hearts did not change regional
mechanical function compared with the infarcted hearts (RSW: 0.032 +/- 0.004,
SAC: 0.037 +/- 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend
toward increase of regional mechanical function compared with the infarcted heart
(RSW: 0.057 +/- 0.011; SAC: 0.051 +/- 0.014, n = 6). Global function showed no
significant differences between any group (p > 0.05); however, there was a trend
toward improved function with the addition of either unseeded or seeded
biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present
in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's
trichrome staining revealed that the greatest infarct size was in the infarct
group (7.0% +/- 2.2%), where unseeded (3.8% +/- 0.6%) and hMSC-seeded (3.7% +/-
0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining
suture area was significantly decreased in the unseeded group compared with that
in the hMSC-seeded group (p < 0.05). This study demonstrated that hMSC-seeded
biological sutures are a method to deliver cells to the infarcted myocardium and
have treatment potential.
PMID- 27610272
TI - Simultaneous analysis of defense-related phytohormones in Arabidopsis thaliana
responding to fungal infection.
AB - PREMISE OF THE STUDY: Simultaneous analysis of defense-related phytohormones can
provide insights into underlying biochemical interactions. Ultra-high-performance
liquid chromatographic (UHPLC) techniques hyphenated to electrospray ionization
mass spectrometry (ESI-MS) are powerful analytical platforms, suitable for
quantitative profiling of multiple classes of metabolites. METHODS: An efficient
and simplified extraction method was designed followed by reverse-phase UHPLC for
separation of seven phytohormones: salicylic acid, methyl salicylate, jasmonic
acid, methyl jasmonate, absiscic acid, indole acetic acid, and the ethylene
precursor 1-aminocyclopropane-1-carboxylic acid. A triple quadrupole multiple
reaction monitoring (MRM) method was developed for MS quantification. The methods
were applied to analyze phytohormones in Arabidopsis leaf tissue responding to
biotic stresses. RESULTS: Under the optimized conditions, the phytohormones were
separated within 15 min, with good linearities and high sensitivity. Repeatable
results were obtained, with the limits of detection and quantification around
0.01 ng/MUL (~9 ng/g tissue). The method was validated and applied to monitor,
quantify, and compare the temporal changes of the phytohormones under biotic
stress. DISCUSSION: Quantitative changes indicate increased production of defense
phytohormones from the various classes. The analytical method was useful and
suitable to distinguish distinctive variations in the phytohormonal profiles and
balance in A. thaliana leaves resulting from pathogen attack.
PMID- 27610273
TI - New development and validation of 50 SSR markers in breadfruit (Artocarpus
altilis, Moraceae) by next-generation sequencing.
AB - PREMISE OF THE STUDY: Using next-generation sequencing technology, new
microsatellite loci were characterized in Artocarpus altilis (Moraceae) and two
congeners to increase the number of available markers for genotyping breadfruit
cultivars. METHODS AND RESULTS: A total of 47,607 simple sequence repeat loci
were obtained by sequencing a library of breadfruit genomic DNA with an Illumina
MiSeq system. Among them, 50 single-locus markers were selected and assessed
using 41 samples (39 A. altilis, one A. camansi, and one A. heterophyllus). All
loci were polymorphic in A. altilis, 44 in A. camansi, and 21 in A.
heterophyllus. The number of alleles per locus ranged from two to 19.
CONCLUSIONS: The new markers will be useful for assessing the identity and
genetic diversity of breadfruit cultivars on a small geographical scale, gaining
a better understanding of farmer management practices, and will help to optimize
breadfruit genebank management.
PMID- 27610274
TI - Development and characterization of 29 polymorphic EST-SSR markers for Stipa
purpurea (Poaceae).
AB - PREMISE OF THE STUDY: Expressed sequence tag-simple sequence repeat (EST-SSR)
markers were developed using Illumina sequencing for further genetic diversity
studies of Stipa purpurea (Poaceae). METHODS AND RESULTS: Twenty-nine polymorphic
and eight monomorphic EST-SSR loci were developed and characterized in 90
individuals from nine S. purpurea populations. The number of alleles per locus
ranged from two to 13, and heterozygosity within populations and total
heterozygosity ranged from 0.04-0.76 and from 0.04-0.87, respectively. Of 37
loci, 12 showed interspecific transferability and polymorphism in a related
species, S. glareosa. CONCLUSIONS: These newly developed EST-SSR primers provide
a useful tool to investigate genetic diversity at the population level and to
analyze the population structure of S. purpurea.
PMID- 27610275
TI - Electrical capacitance as a predictor of root dry weight in shrub willow (Salix;
Salicaceae) parents and progeny.
AB - PREMISE OF THE STUDY: Root biomass is an important trait often disregarded in
woody perennial selection due to the challenge and expense of accurately and
efficiently measuring large populations. In this study, we aim to develop a
simple method that can predict root dry weight within a diverse shrub willow
(Salix) breeding population representing species hybrids and their parents using
root electrical capacitance (REC). METHODS: The REC method was tested on plants
started from cuttings and grown in pots with potting mix in the greenhouse for 11
wk to assess the relationship of REC with 24 biomass traits and its usefulness in
allometric models for root and stem dry biomass. RESULTS: Strong linear and
positive correlations were found between REC and root dry biomass (r = 0.88). The
total proportion of variance of root and stem dry biomass explained by predictors
in multiple regression was 85% and 69%, respectively. The relative importance of
predictor variables in allometric models was dominated by the contribution of
REC. DISCUSSION: This work provides an efficient and nondestructive technique to
indirectly quantify root biomass of genetically diverse shrub willow progeny,
which has great promise for selection of genotypes with varying root biomass and
for the accurate estimation of belowground carbon sequestration.
PMID- 27610276
TI - Development of chloroplast microsatellite markers for the endangered Maianthemum
bicolor (Asparagaceae s.l.).
AB - PREMISE OF THE STUDY: Ten polymorphic chloroplast microsatellite (cpSSR) markers
were developed and characterized in an endemic and endangered herb, Maianthemum
bicolor (Asparagaceae s.l.), for use in conservation genetics. METHODS AND
RESULTS: Primer sets flanking each of the 10 cpSSR loci in noncoding regions of
the chloroplast genome of M. bicolor were designed. These cpSSR markers were
tested on a total of 33 adult individuals from three natural populations in South
Korea. The number of alleles per locus ranged from two to three. The unbiased
haplotype diversity per locus ranged from 0.061 to 0.682. All markers were
successfully transferred to the congeneric species M. japonicum, M. bifolium, and
M. dilatatum with polymorphisms among the species. CONCLUSIONS: The developed
cpSSR markers will be useful in assessing the genetic diversity and population
structure of M. bicolor and will help to infer its molecular identification,
thereby providing a basis for conservation.
PMID- 27610277
TI - Development of microsatellite markers for buffalograss (Buchloe dactyloides;
Poaceae), a drought-tolerant turfgrass alternative.
AB - PREMISE OF THE STUDY: Buchloe dactyloides (Poaceae) is an important component of
Great Plains prairies and a popular drought-tolerant turfgrass alternative in
North America. This species comprises an autopolyploid series, and microsatellite
primers were developed to understand the distribution of genetic variation among
cytotypes and across its large geographic range. METHODS AND RESULTS: Fifteen
microsatellite loci were designed and successfully amplified in six B.
dactyloides populations. Within-population genetic diversity was comparatively
high, consistent with B. dactyloides' life history. Allelic variation at 13 loci
was consistent with the cytotype established in chromosome-counted samples.
CONCLUSIONS: This variable, interpretable set of loci allows for the
determination of multilocus genotype in B. dactyloides individuals of varying
cytotype. Data such as these from a range-wide sample set can provide important
insights for germplasm conservation and crop improvement in this ecologically and
economically important species.
PMID- 27610279
TI - Development of SSR markers for the genus Patellifolia (Chenopodiaceae).
AB - PREMISE OF THE STUDY: Microsatellite primers were developed to promote studies on
the patterns of genetic diversity within Patellifolia patellaris (Chenopodiaceae)
and the relationship between the three species of the genus Patellifolia. METHODS
AND RESULTS: The genomic sequence from P. procumbens was screened for simple
sequence repeats (SSRs), and 3648 SSRs were identified. A subset of 53 SSR
markers was validated, of which 25 proved to be polymorphic in the three species
except for the P. webbiana-specific marker JKIPat16. The number of alleles ranged
from 85 in P. patellaris, 187 in P. procumbens, and 202 in P. webbiana.
CONCLUSIONS: The set of 25 new markers will facilitate studies of the
relationships between the three Patellifolia species and of the spatial and
temporal distribution of genetic diversity within the species.
PMID- 27610278
TI - Microsatellites in the tree Foetidia mauritiana (Lecythidaceae) and utility in
other Foetidia taxa from the Mascarene Islands.
AB - PREMISE OF THE STUDY: Polymorphic markers were required for a native tree of the
Mascarene Islands, Foetidia mauritiana (Lecythidaceae), to investigate the
effects of fragmentation of lowland tropical habitats on tree mating systems and
on gene flow. METHODS AND RESULTS: Using microsatellite enrichment and next
generation sequencing, we identified 13 microsatellite loci (dinucleotide
repeats). They were highly polymorphic in 121 trees sampled in the largest three
populations on Reunion, revealing 2-17 different alleles per locus. Furthermore,
they were found to be polymorphic in conspecific populations on Mauritius and in
F. rodriguesiana from Rodrigues. CONCLUSIONS: These results indicate the utility
of these markers to investigate genetic diversity, mating systems, and gene flow
in a genus native to the biodiversity hotspot of Madagascar and the Indian Ocean
islands.
PMID- 27610280
TI - Transcriptome sequencing and simple sequence repeat marker development for three
Macaronesian endemic plant species.
AB - PREMISE OF THE STUDY: Oceanic islands offer unparalleled opportunities to
investigate evolutionary processes such as adaptation and speciation. However,
few genomic resources are available for oceanic island endemics. In this study,
we publish transcriptome sequences from three Macaronesian endemic plant species
(Argyranthemum broussonetii [Asteraceae], Descurainia bourgaeana [Brassicaceae],
and Echium wildpretii [Boraginaceae]) that are representative of lineages that
have radiated in the region. In addition, the utility of transcriptome data for
marker development is demonstrated. METHODS AND RESULTS: Transcriptomes from the
three plant species were sequenced, assembled, and annotated. Between 1972 and
2282 simple sequence repeats (SSRs) were identified for each taxon. Primers were
designed and tested for 30 of the candidate SSRs identified in Argyranthemum, of
which 12 amplified well across three species and eight were polymorphic.
CONCLUSIONS: We demonstrate here that a single transcriptome sequence is
sufficient to identify hundreds of polymorphic SSR markers. The SSRs are
applicable to a wide range of questions relating to the evolution of island
lineages.
PMID- 27610281
TI - Correction: Retinopathy and Uveitis Associated with Sofosbuvir Therapy for
Chronic Hepatitis C Infection.
AB - [This corrects the article DOI: 10.7759/cureus.597.].
PMID- 27610282
TI - Analysis of Dose Distribution in the Heart for Radiosurgical Ablation of Atrial
Fibrillation.
AB - In a treatment planning study, radiosurgical treatment plans designed to produce
lesions on the left atrium were created using two different methodologies. In
one, structures in the heart (mitral valve and coronary arteries) were designated
as critical structures while this was not done in the second plan. The treatment
plans that were created were compared with standards for heart dose used when
treating spine tumors. Although the dosage for the whole heart greatly exceeded
the dose standards, when only the dose to the ventricles was considered, the plan
where the mitral valve was spared was very close to the dose standards. The
ventricles received a substantially higher dose in the plan where the mitral
valve was not a critical structure. Although neither treatment plan was
delivered, this study demonstrated the feasibility of treating the heart while
minimizing dose to the ventricles.
PMID- 27610283
TI - Correlation of Antiglobulin Reactivity and Severity of Pancytopenia in a Patient
with Hemophagocytic Lymphohistiocytosis: A Case Report and Review of Literature.
AB - A 46-year-old obese male with a medical history of thalassemia minor presented to
the emergency room with complaints of severe fatigue and jaundice worsening over
two weeks. On further evaluation, the patient was found to have significant
hyperbilirubinemia and transaminitis. The hospital course was further complicated
by pancytopenia requiring multiple transfusions, worsening hyperbilirubinemia,
severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. He was
also found to have splenomegaly and evidence of hemophagocytosis on bone marrow
biopsy. On further testing, the patient was also found to have evidence of
hemolysis along with a positive direct Coomb's test consistent with autoimmune
hemolytic anemia (AIHA), and elevated soluble IL-2 receptor level. The patient
was subsequently diagnosed with hemophagocytic lymphohistiocytosis (HLH). He was
treated with HLH-94 protocol along with rituximab for AIHA which resulted in
improvement of patient's condition. We present a case of HLH with no prior
history of autoimmune disease, associated with Coomb's positive AIHA that
resolved after therapy for HLH. Our case also delineates how the intensity of
antiglobulin reactivity, if present, may correlate with severity of the disease,
its progression, and response to treatment.
PMID- 27610284
TI - Analysis of Pulmonary Vein Antrums Motion with Cardiac Contraction Using Dual
Source Computed Tomography.
AB - PURPOSE: The purpose of the study was to determine the extent of displacement of
the pulmonary vein antrums resulting from the intrinsic motion of the heart using
4D cardiac dual-source computed tomography (DSCT). METHODS: Ten consecutive
female patients were enrolled in this prospective planning study. In breath-hold,
a contrast-injected cardiac 4-dimensional (4D) computed tomography (CT)
synchronized to the electrocardiogram was obtained using a prospective sequential
acquisition method including the extreme phases of systole and diastole. Right
and left atrial fibrillation target volumes (CTVR and CTVL) were defined, with
each target volume containing the antral regions of the superior and inferior
pulmonary veins. Four points of interest were used as surrogates for the right
superior and inferior pulmonary vein antrum (RSPVA and RIPVA) and the left
superior and inferior pulmonary vein antrum (LSPVA and LIPVA). On our 4D post
processing workstation (MIM MaestroTM, MIM Software Inc.), maximum displacement
of each point of interest from diastole to systole was measured in the
mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions.
RESULTS: Median age of the enrolled patients was 60 years (range, 56-71 years).
Within the CTVR, the mean displacements of the superior and inferior surrogates
were 3 mm vs. 1 mm (p=0.002), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 0 mm
(p=0.00001), in the ML, AP, and SI directions, respectively. On the left, mean
absolute displacements of the LSPVA vs. LIPVA were similar at 4 mm vs. 1 mm
(p=0.0008), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 1 mm (p=0.00001) in the ML,
AP, and SI directions. CONCLUSION: When isolated from breathing, cardiac
contraction is associated with minimal inferior pulmonary veins motion and modest
(1-6 mm) motion of the superior veins. Target deformation was thus of a magnitude
similar or greater than target motion, limiting the potential gains of cardiac
tracking. Optimal strategies for cardiac radiosurgery should thus either
incorporate the generation of an internal target or cardiac gating. In either
case, cardiac 4D DSCT would allow for personalized margin definition.
PMID- 27610285
TI - Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV
Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy.
AB - PURPOSE: To compare and contrast the patterns of failure in patients with locally
advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment
with primary surgery or radiotherapy +/- chemotherapy. METHODS AND MATERIALS: Two
hundred and thirty-three patients with stage III or IV oropharyngeal squamous
cell carcinoma who underwent curative-intent treatment from 2006-2012, were
reviewed. The median length of follow-up for patients still alive at the time of
analysis was 4.4 years. Data was collected retrospectively from a chart review.
RESULTS: One hundred and thirty-nine patients underwent primary surgery +/-
adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy
(CRT). Demographics were similar between the two groups, except primary
radiotherapy patients had a higher age-adjusted Charleston co-morbidity score
(CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly
only, seven failed locoregionally, and seven failed both distantly and
locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten
distantly alone, and two locoregionally. One patient who underwent radiotherapy
(RT) alone failed distantly. Two and five-year recurrence-free survival rates for
patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five
year recurrence-free survival rates for primary surgery was 80.9% and 76.3%
respectively (p=0.21). There was no significant difference in either treatment
when they were stratified by p16 status or smoking status. CONCLUSIONS: Our
analysis does not show any difference in outcomes for patients treated with
primary surgery or radiotherapy. Although the primary pattern of failure in both
groups was distant metastatic disease, some local failures may be preventable
with careful delineation of target volumes, especially near the base of skull
region.
PMID- 27610286
TI - Minimally Invasive Lumbar Pedicle Screw Fixation Using Cortical Bone Trajectory -
A Prospective Cohort Study on Postoperative Pain Outcomes.
AB - OBJECTIVE: Our study aims to evaluate the clinical outcomes of cortical screws in
regards to postoperative pain. BACKGROUND: Pedicle screw fixation is the current
mainstay technique for posterior spinal fusion. Over the past decade, a new
technique called cortical screw fixation has been developed, which allows for
medialized screw placement through stronger cortical bone. There have been
several studies that showed either biomechanical equivalence or superiority of
cortical screws. However, there is currently only a single study in the
literature looking at clinical outcomes of cortical screw fixation in patients
who have had no prior spine surgery. METHODS: We prospectively looked at the
senior author's patients who underwent cortical versus pedicle lumbar screw
fixation surgeries between 2013 and 2015 for lumbar degenerative disease.
Eighteen patients underwent cortical screw fixation, and 15 patients underwent
traditional pedicle screw fixation. We looked at immediate postoperative pain,
changes in short-term pain (six to 12 weeks post-surgery), and changes in long
term pain (six to eight months). All pain outcomes were measured using a visual
analog scale ranging from 1 to 10. Mann-Whitney or Kruskal-Wallis tests were used
to measure continuous data, and the Fisher Exact test was used to measure
categorical data as appropriate. RESULTS: Our results showed that the cortical
screw cohort showed a trend towards having less peak postoperative pain (p =
0.09). The average postoperative pain was similar between the two cohorts (p =
0.93). There was also no difference in pain six to 12 weeks after surgery (p =
0.8). However, at six to eight months, the cortical screw cohort had worse pain
compared to the pedicle screw cohort (p = 0.02). CONCLUSIONS: The cortical screw
patients showed a trend towards less peak pain in the short-term (one to three
days post-surgery) and more pain in the long-term (six to eight months post
surgery) compared to pedicle screw patients. Both cohorts had a statistically
significant reduction in pain levels compared to preoperative pain. More studies
are needed to further evaluate postoperative pain, long-term functional outcomes,
and fusion rates in patients who undergo cortical screw fixation.
PMID- 27610288
TI - Primary Hydatid Cyst of the Small Intestine: A Rare Case Report and Brief Review
of the Literature.
AB - Hydatid disease is an endemic disease especially in underdeveloped and developing
countries affecting mostly the liver and lungs. The hydatid cysts located in
other sites are mostly due to rupture of primary liver or splenic cysts. We
present a primary small intestine hydatid cyst resected laparoscopically with the
affected intestinal segment. As far as we know, this is the first report of a
primary small intestine hydatid disease in the literature.
PMID- 27610287
TI - Mobile Schwannoma of the Lumbar Spine: A Case Report and Review of the
Literature.
AB - Mobile schwannomas of the spine have been sparsely documented in the literature.
In cases referred to in existing literature, the migratory schwannoma was
documented to occur in the lumbar spine. We added another case to the small
available literature. In our case report, the patient had a previously known
lumbar schwannoma that was being managed conservatively. Due to an acute change
in clinical symptoms, repeat imaging was performed. A magnetic resonance imaging
(MRI) of his spine revealed migration of the schwannoma two levels rostral to his
recent imaging from six weeks earlier. The patient underwent surgical resection
of his lesion. During the operation, the ultrasound was utilized to confirm the
lesion prior to dural opening. In this report, we attempt to provide further
evidence of the utility of an intraoperative ultrasound for intradural lesions
and intend to add to the published literature of mobile schwannomas of the spine.
PMID- 27610290
TI - Large-displacement, hydrothermal frictional properties of DFDP-1 fault rocks,
Alpine Fault, New Zealand: Implications for deep rupture propagation.
AB - The Alpine Fault, New Zealand, is a major plate-bounding fault that accommodates
65-75% of the total relative motion between the Australian and Pacific plates.
Here we present data on the hydrothermal frictional properties of Alpine Fault
rocks that surround the principal slip zones (PSZ) of the Alpine Fault and those
comprising the PSZ itself. The samples were retrieved from relatively shallow
depths during phase 1 of the Deep Fault Drilling Project (DFDP-1) at Gaunt Creek.
Simulated fault gouges were sheared at temperatures of 25, 150, 300, 450, and 600
degrees C in order to determine the friction coefficient as well as the velocity
dependence of friction. Friction remains more or less constant with changes in
temperature, but a transition from velocity-strengthening behavior to velocity
weakening behavior occurs at a temperature of T = 150 degrees C. The transition
depends on the absolute value of sliding velocity as well as temperature, with
the velocity-weakening region restricted to higher velocity for higher
temperatures. Friction was substantially lower for low-velocity shearing (V < 0.3
um/s) at 600 degrees C, but no transition to normal stress independence was
observed. In the framework of rate-and-state friction, earthquake nucleation is
most likely at an intermediate temperature of T = 300 degrees C. The velocity
strengthening nature of the Alpine Fault rocks at higher temperatures may pose a
barrier for rupture propagation to deeper levels, limiting the possible depth
extent of large earthquakes. Our results highlight the importance of strain rate
in controlling frictional behavior under conditions spanning the classical
brittle-plastic transition for quartzofeldspathic compositions.
PMID- 27610289
TI - Effect of dimethylamine on the gas phase sulfuric acid concentration measured by
Chemical Ionization Mass Spectrometry.
AB - Sulfuric acid is widely recognized as a very important substance driving
atmospheric aerosol nucleation. Based on quantum chemical calculations it has
been suggested that the quantitative detection of gas phase sulfuric acid (H2SO4)
by use of Chemical Ionization Mass Spectrometry (CIMS) could be biased in the
presence of gas phase amines such as dimethylamine (DMA). An experiment (CLOUD7
campaign) was set up at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber to
investigate the quantitative detection of H2SO4 in the presence of dimethylamine
by CIMS at atmospherically relevant concentrations. For the first time in the
CLOUD experiment, the monomer sulfuric acid concentration was measured by a CIMS
and by two CI-APi-TOF (Chemical Ionization-Atmospheric Pressure interface-Time Of
Flight) mass spectrometers. In addition, neutral sulfuric acid clusters were
measured with the CI-APi-TOFs. The CLOUD7 measurements show that in the presence
of dimethylamine (<5 to 70 pptv) the sulfuric acid monomer measured by the CIMS
represents only a fraction of the total H2SO4, contained in the monomer and the
clusters that is available for particle growth. Although it was found that the
addition of dimethylamine dramatically changes the H2SO4 cluster distribution
compared to binary (H2SO4-H2O) conditions, the CIMS detection efficiency does not
seem to depend substantially on whether an individual H2SO4 monomer is clustered
with a DMA molecule. The experimental observations are supported by numerical
simulations based on A Self-contained Atmospheric chemistry coDe coupled with a
molecular process model (Sulfuric Acid Water NUCleation) operated in the kinetic
limit.
PMID- 27610291
TI - Cassini observations of ionospheric plasma in Saturn's magnetotail lobes.
AB - Studies of Saturn's magnetosphere with the Cassini mission have established the
importance of Enceladus as the dominant mass source for Saturn's magnetosphere.
It is well known that the ionosphere is an important mass source at Earth during
periods of intense geomagnetic activity, but lesser attention has been dedicated
to study the ionospheric mass source at Saturn. In this paper we describe a case
study of data from Saturn's magnetotail, when Cassini was located at ? 2200 h
Saturn local time at 36 RS from Saturn. During several entries into the
magnetotail lobe, tailward flowing cold electrons and a cold ion beam were
observed directly adjacent to the plasma sheet and extending deeper into the
lobe. The electrons and ions appear to be dispersed, dropping to lower energies
with time. The composition of both the plasma sheet and lobe ions show very low
fluxes (sometimes zero within measurement error) of water group ions. The
magnetic field has a swept-forward configuration which is atypical for this
region, and the total magnetic field strength is larger than expected at this
distance from the planet. Ultraviolet auroral observations show a dawn
brightening, and upstream heliospheric models suggest that the magnetosphere is
being compressed by a region of high solar wind ram pressure. We interpret this
event as the observation of ionospheric outflow in Saturn's magnetotail. We
estimate a number flux between (2.95 +/- 0.43) * 109 and (1.43 +/- 0.21) * 1010
cm-2 s-1, 1 or about 2 orders of magnitude larger than suggested by steady state
MHD models, with a mass source between 1.4 *102 and 1.1 *103 kg/s. After
considering several configurations for the active atmospheric regions, we
consider as most probable the main auroral oval, with associated mass source
between 49.7 +/-13.4 and 239.8 +/-64.8 kg/s for an average auroral oval, and 10
+/-4 and 49 +/-23 kg/s for the specific auroral oval morphology found during this
event. It is not clear how much of this mass is trapped within the magnetosphere
and how much is lost to the solar wind.
PMID- 27610293
TI - Device for easily measuring of the torque of an implant hand driver.
AB - BACKGROUND: As one of the loads applied in implant dentistry, managing the torque
is important for the success of an implant treatment. For this purpose, it is
crucial to ascertain the level of torque being exerted with a hand driver. We
have developed an adapter that makes it easy to measure torque by using a
standard torque wrench in one's possession, rather than with a torquemeter.
PROCEDURES: The head of an abutment screw is cut into a hexagon and pushed into
and fixed to the hexagonal hole (for multi-unit abutments) of a machine driver.
With this, a torque wrench adapter and torque wrench are assembled. A hand driver
is rotated clockwise to the limit, and the torque value is read. RESULTS: It was
possible to read the torque value during screw fastening. CONCLUSIONS: This
technique makes it easy for each dentist to measure the maximum torque that can
be exerted by a hand driver he or she is using. It is even possible to handle
different implant systems.
PMID- 27610294
TI - Numerical solutions and error estimations for the space fractional diffusion
equation with variable coefficients via Fibonacci collocation method.
AB - In this study, the Fibonacci collocation method based on the Fibonacci
polynomials are presented to solve for the fractional diffusion equations with
variable coefficients. The fractional derivatives are described in the Caputo
sense. This method is derived by expanding the approximate solution with
Fibonacci polynomials. Using this method of the fractional derivative this
equation can be reduced to a set of linear algebraic equations. Also, an error
estimation algorithm which is based on the residual functions is presented for
this method. The approximate solutions are improved by using this error
estimation algorithm. If the exact solution of the problem is not known, the
absolute error function of the problems can be approximately computed by using
the Fibonacci polynomial solution. By using this error estimation function, we
can find improved solutions which are more efficient than direct numerical
solutions. Numerical examples, figures, tables are comparisons have been
presented to show efficiency and usable of proposed method.
PMID- 27610295
TI - Parameter optimization in milling of glass fiber reinforced plastic (GFRP) using
DOE-Taguchi method.
AB - INTRODUCTION: Optimization of machining parameters is essential for improving
expected outcome of any machining operation. CASE DESCRIPTION: The aim of this
work is to find out optimum values of machining parameters to achieve minimal
surface roughness during milling operation of GFRP. DISCUSSION AND EVALUATION: In
this machining operation speed, depth of cut and feed rate are considered as
parameters affecting surface roughness and Design of Experiment (DOE)-Taguchi
method tool is used to plan experiments and analyse results. CONCLUSION: Analysis
of experimental results presents optimum values of these three parameters to
achieve minimal surface roughness with speed as a major contributing factor.
Speed-200 rpm, depth of cut-1.2 mm and feed-40 mm/min are an optimal combination
of machining parameter to produce minimal surface roughness during milling of
GFRP.
PMID- 27610292
TI - Comparative profiling of differentially expressed microRNAs between the
follicular and luteal phases ovaries of goats.
AB - To explore if the regulation at post-transcriptional level of follicular phase
(Fols) to luteal phase (Luts) transition occurs in the ovaries of Anhuai goats,
the differentially expressed microRNAs (miRNAs) of ovaries in the Fols and Luts
were analyzed using Solexa sequencing in the study. In total, 320 known miRNAs
were co-expressed in the two phases, 339 and 353 known miRNAs were expressed in
the ovary in the Fols and Luts, respectively. In addition, 45 novel miRNAs were
co-expressed in the two phases, 70 and 94 novel miRNAs were expressed in the
ovary in the Fols and Luts, respectively. Let-7f was the highest expressed
significantly different known miRNA in the two phases, and mir-159 was the
highest expressed significantly different novel miRNA in the two phases, which
may participate in the follicular-luteal transition of Anhuai goats. GO
annotation and KEGG pathway analysis were applied to analyze the target genes of
differentially expressed miRNAs detected in the two phases. The results will help
to further understand the role of miRNAs in the regulation of follicular to
luteal transition in goat ovaries.
PMID- 27610296
TI - The impact of psychological capital on mental health among Iranian nurses:
considering the mediating role of job burnout.
AB - BACKGROUND: The role of nurses in providing high quality healthcare to patients
is so important that creating a desirable working environment to enhance their
overall performance is unavoidable. This paper aimed to explore the impact of
psychological capital on mental health by investigating the mediating effects of
job burnout on this relationship. METHODS AND MATERIAL: The data used in this
research was obtained via a survey conducted among selected Iranian nurses in
public hospitals. In total, 450 questionnaires were distributed and 384 were
completed and returned. Collected data was analysed using Structural Equation
Modelling (SEM). RESULTS: Findings showed that there is a significant
relationship between psychological capital, job burnout and mental health; also,
there is a significant negative relationship between psychological capital and
job burnout, and a significant positive relationship between psychological
capital and mental health. CONCLUSION: The results have several important
practical implications for human resource management in Iranian public hospitals.
According to the results of this study, reducing job burnout is an important
factor in enhancing psychological capital and can positively enhance nurses'
mental health.
PMID- 27610298
TI - Exact solution of cilia induced flow of a Jeffrey fluid in an inclined tube.
AB - The present study investigated the cilia induced flow of MHD Jeffrey fluid
through an inclined tube. This study is carried out under the assumptions of long
wavelength and low Reynolds number approximations. Exact solutions for the
velocity profile, pressure rise, pressure gradient, volume flow rate and stream
function are obtained. Effects of pertinent physical parameters on the
computational results are presented graphically.
PMID- 27610297
TI - Increased migraine risk in osteoporosis patients: a nationwide population-based
study.
AB - BACKGROUND: Osteoporosis and migraine are both important public health problems
and may have overlapping pathophysiological mechanisms. The aim of this study was
to use a Taiwanese population-based dataset to assess migraine risk in
osteoporosis patients. METHODS: The Taiwan National Health Insurance Research
Database was used to analyse data for 40,672 patients aged >=20 years who had
been diagnosed with osteoporosis during 1996-2010. An additional 40,672 age
matched patients without osteoporosis were randomly selected as the non
osteoporosis group. The relationship between osteoporosis and migraine risk was
estimated using Cox proportional hazard regression models. RESULTS: During the
follow-up period, 1110 patients with osteoporosis and 750 patients without
osteoporosis developed migraine. After controlling for covariates, the overall
incidence of migraine was 1.37-fold higher in the osteoporosis group than in the
non-osteoporosis group (3.72 vs. 1.24 per 1000 person-years, respectively).
Migraine risk factors included high Charlson Comorbidity Index score, female
gender, hypertension, depression, asthma, allergic rhinitis, obesity, and tobacco
use disorder. CONCLUSIONS: Our results indicate that patients with a history of
osteoporosis had a higher risk of migraine.
PMID- 27610299
TI - Successful management of dexmedetomidine for postoperative intensive care
sedation in a patient with anti-NMDA receptor encephalitis: a case report and
animal experiment.
AB - BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis is a
recently identified but increasingly recognized autoimmune paraneoplastic
disease. Because these patients present complex neuropsychiatric symptoms due to
NMDA-R dysfunction, the optimal methods of sedation/anesthesia remain
controversial. Here, we present animal experiment data, along with a related case
report, implying the safe and effective use of dexmedetomidine in patients with
anti-NMDA-R encephalitis. FINDINGS: (1) Animal experiment: in order to
investigate whether dexmedetomidine may interfere with NMDA-R activity, an NMDA
antagonist (MK-801) model in rats was used to simulate anti-NMDA-R encephalitis.
Administration of MK-801 produced well-characterized schizophrenia-like
behaviors, i.e. hyperlocomotion and stereotyped sniffing. Ketamine, an NMDA
receptor-dependent anesthetic, exaggerated both behaviors, even at sub-anesthetic
doses. On the other hand, dexmedetomidine did not show any exacerbation,
suggesting that dexmedetomidine has no clinically relevant interaction with the
NMDA-R in vivo. (2) CASE REPORT: our patient, a 27-year-old female, was diagnosed
with anti-NMDA-R encephalitis secondary to ovarian teratoma. She underwent
laparoscopic ovariectomy under general anesthesia using thiopental, sevoflurane,
and remifentanil, which were well tolerated. After transfer to the intensive care
unit, she became increasingly agitated despite repeated boluses of intravenous
fentanyl. Infusion of dexmedetomidine (0.5-1.0 MUg/kg/h) was started, and an
adequate level of sedation was achieved uneventfully. After discontinuation of
dexmedetomidine, recovery from sedation was smooth and quick without any
deterioration of neurological or psychological symptoms. CONCLUSIONS: Our
experimental findings and the presented case suggest that dexmedetomidine may be
safely used in patients with anti-NMDA-R encephalitis. Further clinical
evaluation is warranted to validate this finding.
PMID- 27610300
TI - Antibiotic susceptibility pattern and analysis of plasmid profiles of Pseudomonas
aeruginosa from human, animal and plant sources.
AB - Multidrug resistant organisms (MDROs) constitute a major public health threat
globally. Clinical isolates of Pseudomonas aeruginosa remains one of the most
studied MDROs however there is paucity of information regarding the
susceptibility of its animal and plants isolates to antipseudomonas drug in
Nigeria. From a total of 252 samples consisting of plants, animals and clinical
samples, 54, 24 and 22 P. aeruginosa were isolated from vegetables, animals and
clinical sources respectively. All the isolates were identified by standard
biochemical methods. Antimicrobial susceptibility testing (AST) of the 100 P.
aeruginosa isolates against 7 antipseudomonal drugs was carried out by disk
diffusion method, the phenotypic detection of ESBL was done by double disk
synergy test (DDST) while plasmid extraction on 20 selected isolates based on
their resistance to 2 or more classes of antibiotics was carried out by alkaline
lysis method and analysed with Lambda DNA/Hind lll marker respectively. The AST
results revealed highest resistance of 91 and 55 % to ceftazidime and
carbenicillin respectively while highest susceptibilities of 99 % for
piperacillin-tazobactam and imipenem were recorded in overall assay. Fifteen out
of 100 isolates specifically (10) from vegetables, (3) clinical and (2) poultry
isolates showed synergy towards the beta-lactamase inhibitor indicating
production of ESBL by DDST method. Detection of plasmids was among vegetable (n =
4), poultry (n = 4), cow (n = 3) and clinical isolates (n = 1). Plasmid profile
for the selected isolates revealed 6 of the strains had one plasmids each while 5
strains possessed 2-4 plasmids and 1 strain had 5 plasmids. The sizes of the
plasmid range from <1 to >=23kbp. Detection of ESBL and Plasmids among the
investigated isolates is suggestive of multiple interplay of resistance mechanism
among the isolates. Plants and animal isolates of P. aeruginosa harbouring
multiple mechanisms of resistance is of concern due to the danger it poses on the
public health.
PMID- 27610301
TI - Antibacterial activity identification of pCM19 and pCM12 derived from hGlyrichin.
AB - BACKGROUND: hGlyrichin is a novel human antimicrobial peptide rich in glycine.
The previous study of known human antimicrobial peptides indicated that in an
eligible range, the greater corresponding antibacterial activity was consisted
with the shorter peptide sequence. FINDINGS: Two peptides named pCM19 and pCM12
were synthesized and the antibacterial activity assay results showed that these
peptides exhibited strong antibacterial activity that was inversely proportional
to the length of the peptide. Despite the effective inhibition of bacterial
growth, the synthetic peptides showed no hemolytic effect on human red blood
cells. CONCLUSIONS: Taken together, these two peptides derived from hGlyrichin
both have strong antibacterial activity and are not toxic to human somatic cells.
PMID- 27610302
TI - The electrospinning of the copolymer of styrene and butyl acrylate for its
application as oil absorbent.
AB - Electrospun polystyrene materials have been employed as oil absorbents, but they
have visible drawbacks such as poor strength at low temperature and unreliable
integrity because of brittleness and insufficient cohesive force among fibers.
Butyl acrylate can polymerize into flexible chains, and its polymer can be used
as elastomer and adhesive material. Thereby it is possible to obtain the material
that has better performance in comparison with electrospun polystyrene material
through the electrospinning of the copolymer of styrene and butyl acrylate. In
this work, a polymer was synthesized through suspension polymerization by using
styrene and butyl acrylate as comonomers. The synthesis of the copolymer of
styrene and butyl acrylate was verified through dissolution and hydrolysis
experimental data; as well through nuclear magnetic resonance spectrometry. The
viscous flow activation energy of the solution consisting of copolymer and N, N
dimethylformamide was determined via viscosity method and then adopted to
establish the entanglement characteristics of butyl acrylate's chain segments.
Finally, in order to electrospin the copolymer solution into fibrous membrane,
the effects of monomer feed ratio and spinning parameters were investigated. The
prepared fibrous membrane was found to have a potential use as oil absorbent.
PMID- 27610303
TI - MATLAB-based algorithm to estimate depths of isolated thin dike-like sources
using higher-order horizontal derivatives of magnetic anomalies.
AB - This paper presents an easy-to-use open source computer algorithm (code) for
estimating the depths of isolated single thin dike-like source bodies by using
numerical second-, third-, and fourth-order horizontal derivatives computed from
observed magnetic anomalies. The approach does not require a priori information
and uses some filters of successive graticule spacings. The computed higher-order
horizontal derivative datasets are used to solve nonlinear equations for depth
determination. The solutions are independent from the magnetization and ambient
field directions. The practical usability of the developed code, designed in
MATLAB R2012b (MathWorks Inc.), was successfully examined using some synthetic
simulations with and without noise. The algorithm was then used to estimate the
depths of some ore bodies buried in different regions (USA, Sweden, and Canada).
Real data tests clearly indicated that the obtained depths are in good agreement
with those of previous studies and drilling information. Additionally, a state-of
the-art inversion scheme based on particle swarm optimization produced comparable
results to those of the higher-order horizontal derivative analyses in both
synthetic and real anomaly cases. Accordingly, the proposed code is verified to
be useful in interpreting isolated single thin dike-like magnetized bodies and
may be an alternative processing technique. The open source code can be easily
modified and adapted to suit the benefits of other researchers.
PMID- 27610304
TI - Rebuilding DEMATEL threshold value: an example of a food and beverage information
system.
AB - This study demonstrates how a decision-making trial and evaluation laboratory
(DEMATEL) threshold value can be quickly and reasonably determined in the process
of combining DEMATEL and decomposed theory of planned behavior (DTPB) models.
Models are combined to identify the key factors of a complex problem. This paper
presents a case study of a food and beverage information system as an example.
The analysis of the example indicates that, given direct and indirect
relationships among variables, if a traditional DTPB model only simulates the
effects of the variables without considering that the variables will affect the
original cause-and-effect relationships among the variables, then the original
DTPB model variables cannot represent a complete relationship. For the food and
beverage example, a DEMATEL method was employed to reconstruct a DTPB model and,
more importantly, to calculate reasonable DEMATEL threshold value for determining
additional relationships of variables in the original DTPB model. This study is
method-oriented, and the depth of investigation into any individual case is
limited. Therefore, the methods proposed in various fields of study should
ideally be used to identify deeper and more practical implications.
PMID- 27610306
TI - Implementation of rectangular slit-inserted ultra-wideband tapered slot antenna.
AB - In this paper, a tapered slot antenna capable of ultra-wideband communication was
designed. In the proposed antenna, rectangular slits were inserted to enhance the
bandwidth and reduce the area of the antenna. The rectangular slit-inserted
tapered slot antenna operated at a bandwidth of 8.45 GHz, and the bandwidth
improved upon the basic tapered slot antenna by 4.72 GHz. The radiation pattern
of the antenna was suitable for location recognition in a certain direction owing
to an appropriate 3 dB beam width. The antenna gain was analyzed within the
proposed bandwidth, and the highest gain characteristic at 7.55 dBi was exhibited
at a 5-GHz band. The simulation and measurement results of the proposed tapered
slot antenna were similar.
PMID- 27610305
TI - Information provision and attentive listening as determinants of patient
perceptions of shared decision-making around chronic illnesses.
AB - BACKGROUND: While chronic illnesses are a major concern of the health system
worldwide, little is known about patients-physicians communication. Growing
demand for patient-centered care and shared decision-making have increased the
interest for patients-physicians communication. Based on previous literature, we
propose a model in which the effect of information provision and attentive
listening over patients' perceptions of shared decision-making (PPSDM) is
mediated by the variables self-efficacy and proactivity. Primary data were
collected between April and August 2014 through an online survey of patients with
haemophilia. Haemophilia is a chronic disease in which many options of treatment
are available. The right option depends, to some extent, on patient's
preferences. In this context, great uncertainty exists when choosing treatment
option and shared decision-making plays an essential role. RESULTS: A total of
181 patients with haemophilia participated in the survey. The psychometric
properties of the measurement scales were evaluated by means of a confirmatory
factor analysis. A structural equation model was designed. Results show that
provision of information and attentive listening determine PPSDM through
patients' self-efficacy and proactivity in requesting information. CONCLUSIONS:
It is important to incorporate communication training in medical education,
particularly provision of information and attentive listening. These skills help
the healthcare professional to gain a deeper understanding of the patient.
Furthermore, provision of information and attentive listening are fundamental in
helping patients not to undervalue their personal knowledge and expertise in
relation to their doctors. These strategies encourage them to adopt a more active
position in requesting information. Encouraging a proactive behaviour of patients
and their relatives helps them to realize the need to participate and to make
them feel that they are part of the decision-making process.
PMID- 27610307
TI - The radius of influence of a combined method of in situ air sparging and soil
vapor extraction in the intertidal sediments of Gomso Bay on the west coast of
South Korea.
AB - BACKGROUND: In situ air sparging (IAS) was undertaken at sites in the tidal flats
of Mandol and Hajeon, on the west coast of South Korea, to estimate variations in
the radius of influence (ROI). RESULTS: The Mandol core sample consisted of sand
and muddy sand 1.6-3.4 [Formula: see text] (average 2.3 [Formula: see text]) and
contained water (average 15.10 %). The Hajeon core sample consisted of muddy
sand, sandy silt, and muddy sandy gravel 1.31-4.44 [Formula: see text] (average
3.11 [Formula: see text]) and contained water (average 19.77 %). These sites
differ in their sedimentary and geochemical characteristics. At the Mandol site,
no H2S or combustible gas was detected during a 48-h sampling period, except for
some volatile organic compounds (0.1-2.0 ppm) at the monitoring well during the
initial 30 min. At the soil vapor extraction wells, CO2 and O2 varied by 850 ppm
(690-1540 ppm) and 0.5 % (20.4-20.9 %), respectively. At the Hajeon site, CO2 and
O2 varied from 580 to 1250 ppm and 20.6 to 20.9 %, respectively, during the 48-h
sampling period. CONCLUSIONS: At the Mandol site, an oxygen concentration of 20.6
% was assumed as the effective concentration, and the ROI was estimated to be
128.0 cm. However, at the Hajeon site the ROI was estimated to be 85.7 cm. The
smaller effective ROI at the Hajeon site was likely caused by the thin aquifer
and thin screens of the sparing well. This estimated ROI show that the
remediation effectiveness varies greatly as a heterogeneities and anisotropies in
the porous sediments. Besides, injection pressure, flow rate, pulsing or
continuous mode, and the range of intrinsic permeability for most important
characteristic of sediment (soil) type impacted the ROI. Therefore, the IAS
method is more effective at a pervasive air flow sediments such as Mandol, which
consists of sand and muddy sand than at a channelized site such as Hajeon.
PMID- 27610309
TI - On the temporal interpretation of certain surprise questions.
AB - This article considers a special kind of surprise questions, i.e. those
introduced by the adversative particle ma (but), and compares it with surprise
exclamations. The main issue addressed here concerns the obligatory presence in
the questions of the imperfect verbal form, versus the obligatory presence in
exclamations of a non-imperfect indicative. It will be shown that the special
semantics associated with these structures determines the presence of a certain
verbal form. Some syntactic issues will be addressed in the final section, having
to do with the representation in the syntax of properties connected to the
context.
PMID- 27610308
TI - Improving GPU-accelerated adaptive IDW interpolation algorithm using fast kNN
search.
AB - This paper presents an efficient parallel Adaptive Inverse Distance Weighting
(AIDW) interpolation algorithm on modern Graphics Processing Unit (GPU). The
presented algorithm is an improvement of our previous GPU-accelerated AIDW
algorithm by adopting fast k-nearest neighbors (kNN) search. In AIDW, it needs to
find several nearest neighboring data points for each interpolated point to
adaptively determine the power parameter; and then the desired prediction value
of the interpolated point is obtained by weighted interpolating using the power
parameter. In this work, we develop a fast kNN search approach based on the space
partitioning data structure, even grid, to improve the previous GPU-accelerated
AIDW algorithm. The improved algorithm is composed of the stages of kNN search
and weighted interpolating. To evaluate the performance of the improved
algorithm, we perform five groups of experimental tests. The experimental results
indicate: (1) the improved algorithm can achieve a speedup of up to 1017 over the
corresponding serial algorithm; (2) the improved algorithm is at least two times
faster than our previous GPU-accelerated AIDW algorithm; and (3) the utilization
of fast kNN search can significantly improve the computational efficiency of the
entire GPU-accelerated AIDW algorithm.
PMID- 27610310
TI - Multi-objective optimization of MOSFETs channel widths and supply voltage in the
proposed dual edge-triggered static D flip-flop with minimum average power and
delay by using fuzzy non-dominated sorting genetic algorithm-II.
AB - BACKGROUND: D Flip-Flop as a digital circuit can be used as a timing element in
many sophisticated circuits. Therefore the optimum performance with the lowest
power consumption and acceptable delay time will be critical issue in electronics
circuits. FINDINGS: The newly proposed Dual-Edge Triggered Static D Flip-Flop
circuit layout is defined as a multi-objective optimization problem. For this, an
optimum fuzzy inference system with fuzzy rules is proposed to enhance the
performance and convergence of non-dominated sorting Genetic Algorithm-II by
adaptive control of the exploration and exploitation parameters. By using
proposed Fuzzy NSGA-II algorithm, the more optimum values for MOSFET channel
widths and power supply are discovered in search space than ordinary NSGA types.
What is more, the design parameters involving NMOS and PMOS channel widths and
power supply voltage and the performance parameters including average power
consumption and propagation delay time are linked. To do this, the required
mathematical backgrounds are presented in this study. CONCLUSION: The optimum
values for the design parameters of MOSFETs channel widths and power supply are
discovered. Based on them the power delay product quantity (PDP) is 6.32 PJ at
125 MHz Clock Frequency, L = 0.18 um, and T = 27 degrees C.
PMID- 27610311
TI - Relation between unconjugated bilirubin and RDW, neutrophil to lymphocyte ratio,
platelet to lymphocyte ratio in Gilbert's syndrome.
AB - BACKGROUND: Unconjugated bilirubin (UCB) plays a protective role in coronary
artery disease. Red cell distribution width (RDW), neutrophil to lymphocyte ratio
(NLR) and platelet to lymphocyte ratio (PLR) are inflammatory biomarkers and
higher levels are related to atherosclerosis and adverse cardiovascular events.
AIM: We aimed to investigate the relation between UCB levels and RDW, NLR, PLR in
people with Gilbert's syndrome (GS). MATERIALS AND METHODS: We selected 2166
subjects (1082 with GS and 1084 healthy controls) from a database having 33,695
people. RDW, NLR and PLR were investigated in the subjects with GS and compared
with the healthy controls. Linear regression analysis was used to evaluate the
relation between variables. RESULTS: NLR and PLR were higher in the subjects with
GS compared to the controls (p < 0.001). RDW was similar in both groups (p =
0.318). UCB was negatively correlated with lymphocyte counts (p = 0.040), and
positively correlated with RDW (p < 0.001) and PLR (p = 0.037) in the subjects
with GS. There was no significant correlation between UCB and NLR (p = 0.078).
RDW (p < 0.001) and lymphocyte counts (p = 0.030) were significantly associated
with UCB levels in the regression analysis conducted in the subjects with GS.
CONCLUSION: There is a negative association between UCB and NLR, PLR due to low
amounts of lymphocyte counts, which causes increased risk of CVD. These results
suggest that the cardio-protective effect of UCB is due to both anti-oxidative
and anti-inflammatory ways indirectly.
PMID- 27610312
TI - Thermal imaging of soybean response to drought stress: the effect of Ascophyllum
nodosum seaweed extract.
AB - Previous experiments have demonstrated positive effect of Acadian((r)) extract of
Ascophyllum nodosum on plant stress-resistance, however the mode of action is not
fully understood. The aim of this study was to understand the physiological
effect of Acadian((r)) seaweed extract on the plant response to drought stress.
Leaf temperature and leaf angle were measured as early-stage indicators of plant
stress with thermal imaging "in situ" over a 5-day stress-recovery trial. The
early stress-response of control became visible on the third day as a rapid
wilting of leaves, accompanied with the asymptotic increase of leaf temperature
on 4-5 degrees C to the thermal equilibrium with ambient air temperature. At the
same time Acadian((r)) treated plants still maintained turgor, accompanied with
the linear increase in leaf temperature, which indicated better control of
stomatal closure. Re-watering on the fifth day showed better survival of treated
plants compared to control. This study demonstrated the ability of Acadian((r))
seaweed extract to improve resistance of soybean plants to water stress.
PMID- 27610313
TI - Alkali basalts and enclosed ultramafic xenoliths near Ushuaia, Tierra Del Fuego,
Argentina.
AB - At the southernmost part of Tierra del Fuego a few outcrops and erratic boulders
of alkali basaltic rocks with ultramafic enclaves have been studied. Alkali
basalt plugs or pipes hitherto identified are scarce, and host rocks are
constituted by slates that belong to Mesozoic deposition. The petrography,
texture and composition of the basalt and xenoliths were investigated by
petrographic microscope and electron microprobe analysis. Xenocrysts of amphibole
and alkali feldspar, phenocrysts of nepheline, olivine, spinel, phlogopite and Fe
Ti minerals (10 %) and a diversity of xenoliths, mainly lherzolitic, pyroxenite
and wehrlitic nodules (15 %), but also from metamorphic rocks provenance, are
contained in the basalt groundmass (75 %). This finer-grained material is made up
of laths or needles of plagioclase, pyroxene, opaque minerals, apatite and glass,
with intersertal, hyalopilitic and pilotaxitic. Locally, rock has an even
granoblastic texture. Former amygdules are filled by analcite, zeolites, sodalite
and calcite. The normative classification, based on nepheline content, conclude
that this rock is an alkali basalt. The chemical classification, considering
immobile elements as Zr/TiO2 versus Nb/Y indicate an alkali basalt too and plots
over the TAS diagram fall in the foidite (Na-rich or nephelinite) and basanite
fields. The REE patterns are fractionated (La/Yb primitive mantle normalized is
approximately 30). The K-Ar isotopic technique on individual macrocrysts gave
ages of 146 +/- 5 Ma (amphibole) and 127 +/- 4 Ma (alkali feldspar); and K-Ar
whole rock datum reported 8.3 +/- 0.3 Ma. Nevertheless, fertile samples show
geochemical features typical of deep derived material thus, based on the position
in the actual tectonic setting, indicate that the basalt is older than its
isotopic age.
PMID- 27610314
TI - A wireless sensor system for a biofeedback training of hammer throwers.
AB - Hammer-throw has a long-standing history in track and field, but unlike some
other sports events, men's hammer throw has not seen a new world record since
1986. One of the possible reasons for this stagnation could be the lack of real
time biomechanical feedback training. In this study, we proposed to establish
scientifically described training targets and routes, which in turn required
tools that could measure and quantify characteristics of an effective hammer
throw. Towards this goal, we have developed a real-time biomechanical feedback
device-a wireless sensor system-to help the training of hammer-throw. The system
includes two sensors-an infrared proximity sensor for tracing the hip vertical
movement and a load cell for recording the wire tension during a hammer-throw.
The system uses XBees for data transmission and an Arduino processor for data
processing and system control. The results revealed that the wire tension
measurement could supply sufficient key features for coaches to analyze hammer
throw and give real-time feedback for improving training efficiency.
PMID- 27610315
TI - Genetic rules for the dermatoglyphics of human fingertips and their role in
spouse selection: a preliminary study.
AB - OBJECTIVE: We assessed the genetic rules for the dermatoglyphics of human
fingertips. We also evaluated the correlation between spouse selection with the
number of whorls on fingertips. METHODS: Data were collected for the number of
whorls from 118 families (couples and their children). Distribution of whorls was
analyzed further to investigate the relationship between heredity and spouse
selection. RESULTS: Through multiple regression analysis, we found that the
number of whorls on fingertips was affected considerably by genetic factors. In a
married couple with a moderate number of whorls, the probability of their
children having a high number of whorls was 26.5 %, and the probability of their
children having a low number of whorls was 23.5. These values were close to the
theoretical value (25 %). A significant correlation between whorl count between
spouses was observed. CONCLUSION: These data suggest that whorls are inherited
from a single gene or a group of closely linked genes. Our findings provide an
initial insight on the potential contribution of biologic characteristics on
spouse selection.
PMID- 27610317
TI - Langerhans cell histiocytosis in the adult lumbar spine: case report.
AB - INTRODUCTION: Langerhans cell histiocytosis (LCH) occurs rarely in the spine of
adults. The radiological findings usually resemble vertebral tumors. Etiology of
LCH has not been clearly established yet. Therapeutic approaches are still
controversial. We describe a case of LCH in an adult spine. CASE DESCRIPTION: A
patient who presented with low back pain had an osteolytic lesion in the L1
vertebral body without neurological deficits, and fluoroscopy-guided needle
biopsy of the L1 vertebral body was performed. The immunohistochemical diagnosis
confirmed LCH. The patient was successfully treated with conservative methods.
DISCUSSION: The choice of appropriate therapy is very important, with treatment
options varying from watch-and to aggressive treatment. CONCLUSION: LCH is
considered as a pediatric disease that is extremely rare in the spine of adults
and should be include in the differential diagnosis of osteolytic vertebral
lesions. Conservative treatment is best choice for a patient with LCH without
neurological deficit or spinal instability.
PMID- 27610316
TI - Transmission of Enterobacter aerogenes septicemia in healthcare workers.
AB - Enterobacter aerogenes is recognized as an important bacterial pathogen in
hospital-acquired infections. This report describes two unusual cases of
septicemia caused by E. aerogenes in immunocompetent healthcare workers. E.
aerogenes was isolated from blood cultures of the two patients experiencing
septicemia. The clinical isolates were initially identified as E. aerogenes using
a VITEK II automated system and 16S rRNA sequence analysis, and; both isolates
involved in the outbreak shared a common pulse-field gel electrophoresis pattern.
The similarities between the two cases included the simultaneous development of
gastroenteritis symptoms, severe sepsis and thrombocytopenia after taking
intravenous injections of ketorolac tromethamine. A common source of normal
saline, a 100 mL bottle, was used for diluting the analgesic in both cases. In
addition to the general population, healthcare workers, especially those who are
also intravenous drug abusers, should be considered subjects that could cause a
transmission of Enterobacter infection.
PMID- 27610318
TI - Effects of exogenous enzymes and application method on nutrient intake,
digestibility and growth performance of Pelibuey lambs.
AB - Pelibuey sheep is the main breed in the tropical and subtropical regions of
Mexico, and high demand of sheep meat has favored the finishing of lambs in
feedlots with diets containing high levels of grains. The objective of this study
was to evaluate the effects of exogenous enzymes (EE) and application method on
nutrient intake and digestibility and performance of growing Pelibuey lambs.
Treatments were based on comparison of two different methods of adding an enzyme
product (sprayed on the total mixed ration or applied orally to the lambs) versus
control treatment (no added enzyme). Twenty-one Pelibuey lambs, weighing 15.7 kg
(SD = 1.8 kg) initial body weight, were individually housed in shaded pens and
assigned randomly to one of the three enzyme treatments. At the end of study
(lasting for 45 days), three lambs from each treatment were randomly selected and
adapted to a pants and harness designed for fecal collection to measure nutrient
digestibilities. Total body gain and average daily gain were affected (P < 0.05)
by supplemental EE. The application method of EE had significant (P < 0.05)
effect on FCE and FCR, but no effects were observed on nutrient intake.
Supplemental EE did improve (P < 0.05) the digestibilities of dry matter, organic
matter, neutral and acid detergent fiber, but no differences were observed in
crude protein digestibility. The application method of EE had significant (P <
0.05) effect on the digestibility of acid detergent fiber. Supplemental EE can
improve body weight gain and nutrient digestibilities without affecting nutrient
intake in Pelibuey lambs, but the results of feed conversion efficiency and acid
detergent fiber digestibility depend on the application method used of the EE.
PMID- 27610319
TI - A new numerical approach to solve Thomas-Fermi model of an atom using bio
inspired heuristics integrated with sequential quadratic programming.
AB - In this study, a novel bio-inspired computing approach is developed to analyze
the dynamics of nonlinear singular Thomas-Fermi equation (TFE) arising in
potential and charge density models of an atom by exploiting the strength of
finite difference scheme (FDS) for discretization and optimization through
genetic algorithms (GAs) hybrid with sequential quadratic programming. The FDS
procedures are used to transform the TFE differential equations into a system of
nonlinear equations. A fitness function is constructed based on the residual
error of constituent equations in the mean square sense and is formulated as the
minimization problem. Optimization of parameters for the system is carried out
with GAs, used as a tool for viable global search integrated with SQP algorithm
for rapid refinement of the results. The design scheme is applied to solve TFE
for five different scenarios by taking various step sizes and different input
intervals. Comparison of the proposed results with the state of the art numerical
and analytical solutions reveals that the worth of our scheme in terms of
accuracy and convergence. The reliability and effectiveness of the proposed
scheme are validated through consistently getting optimal values of statistical
performance indices calculated for a sufficiently large number of independent
runs to establish its significance.
PMID- 27610320
TI - Associations between peripheral blood eosinophil counts in patients with systemic
sclerosis and disease severity.
AB - Increased levels of serum pro-fibrotic cytokines have been reported in patients
with systemic sclerosis (SSc). Some of these cytokines also play an important
role in the differentiation and migration of eosinophils. The aim of this study
was to determine whether eosinophilic inflammation is caused in SSc. We
retrospectively reviewed the peripheral blood eosinophil counts in 70 untreated
patients with SSc and compared them with those in patients with other major
collagen diseases. We additionally evaluated a possible association with disease
severity. Eosinophil counts were significantly higher levels in patients with SSc
than in those with other collagen diseases, whereas total leukocyte counts were
not. Eosinophil counts correlated positively with both severe interstitial lung
disease (ILD; r = 0.255, p = 0.033) and modified Rodnan total skin thickness
score (m-Rodnan TSS) in SSc (r = 0.347, p = 0.003), but did not correlate with
ILD severity in other collagen diseases. In conclusion, peripheral eosinophil
counts were higher in patients with SSc than in those with other collagen
diseases and were correlated with increased disease severity. Our data suggest
that eosinophilic inflammation is involved in the pathogenesis and progression of
SSc.
PMID- 27610321
TI - A photon counting and a squeezing measurement method by the exact absorption and
dispersion spectrum of Lambda-type Atoms.
AB - Recently, the master equations for the interaction of two-mode photons with a
three-level Lambda-type atom are exactly solved for the coherence terms. In this
paper the exact absorption spectrum is applied for the presentation of a non
demolition photon counting method, for a few number of coupling photons, and its
benefits are discussed. The exact scheme is also applied where the coupling
photons are squeezed and the photon counting method is also developed for the
measurement of the squeezing parameter of the coupling photons.
PMID- 27610322
TI - Analysis and performance assessment of a fragment retransmission scheme for
energy efficient IEEE 802.11 WLANs.
AB - Backoff-free fragment retransmission (BFFR) scheme enhances the performance of
legacy MAC layer fragmentation by eliminating contention overhead. The eliminated
overhead is the result of backoff executed before a retransmission attempt is
made when fragment transmission failure occurs within a fragment burst. This
paper provides a mathematical analysis of BFFR energy efficiency and further
assesses, by means of simulations, the energy efficiency, throughput and delay
obtained when BFFR is used. The validity of the new scheme is evaluated in
different scenarios namely, constant bit rate traffic, realistic bursty internet
traffic, node mobility, rigid and elastic flows and their combinations at
different traffic loads. We also evaluate and discuss the impact of BFFR on MAC
fairness when the number of nodes is varied from 4 to 10. It is shown that BFFR
has advantages over legacy MAC fragmentation scheme in all the scenarios.
PMID- 27610323
TI - Numerical method to compute acoustic scattering effect of a moving source.
AB - In this paper, the aerodynamic characteristic of a ducted tail rotor in hover has
been numerically studied using CFD method. An analytical time domain formulation
based on Ffowcs Williams-Hawkings (FW-H) equation is derived for the prediction
of the acoustic velocity field and used as Neumann boundary condition on a rigid
scattering surface. In order to predict the aerodynamic noise, a hybrid method
combing computational aeroacoustics with an acoustic thin-body boundary element
method has been proposed. The aerodynamic results and the calculated sound
pressure levels (SPLs) are compared with the known method for validation.
Simulation results show that the duct can change the value of SPLs and the sound
directivity. Compared with the isolate tail rotor, the SPLs of the ducted tail
rotor are smaller at certain azimuth.
PMID- 27610324
TI - Nutrients and phytoplankton dynamics in the fishing grounds off Tiruchendur
coastal waters, Gulf of Mannar, India.
AB - Nutrients and phytoplankton dynamics in the traditional fishing grounds off
Tiruchendur coast, Gulf of Mannar, India revealed a clear seasonal trend
influenced by prevailing monsoon system in east coast of India. A total of 73
species of phytoplankton were identified from the fishing grounds, revealed
higher abundance in summer months compared to other seasons. Among the three
stations, maximum phytoplankton abundance was recorded in station 2 followed by
stations 1 and 3. The phytoplankton abundance ranged from 2.85 * 10(4) to 6.34 *
10(4) cells/l, with higher and lower value observed during summer and post
monsoon season respectively. Chl-a showed similar seasonal trend with
phytoplankton abundance and fluctuated from 0.4 to 6.8 mg/m(3) with high
concentrates were recorded during summer. Primary productivity was ranged from
13.8 to 28.7 mg, C/m(2)/day with maximum and minimum during summer and monsoon
respectively. It was understood from the study, ammonia could be acting as the
limiting nutrient for phytoplankton growth, while the role of nitrate, nitrite,
phosphate and silicate remained insignificant. At the time of diatom population
proliferates there was a drop in the nutrient levels was observed during the
study. The water current flowing from north to south during the northeast
monsoon, nutrient rich fresh water discharged from Tamirabarani River influencing
the nutrient dynamics in the fishing grounds that are ultimately increasing the
nutrients concentration during northeast monsoon.
PMID- 27610325
TI - Phosphorus fractionation distribution in Guapimirim estuary: SE Brazil.
AB - The Guapimirim estuary is the main tributary of Guanabara bay and is located in
the northeast portion. Although it is protected, this estuary has been
experiencing strong anthropogenic pressure, which has led to changes in the
natural characteristics. Large amounts of sewage are dumped into the bay through
tributaries, thereby changing the water and bottom sediment quality. One of the
main elements of sewage is phosphorus. Despite its importance to life, a high
concentration of this nutrient in the environment can result in eutrophication.
This work describes the phosphorus distribution in its different fractions in the
bottom sediment at 16 stations located in the main channel of the Guapimirim
estuary. These results are correlated with data on grain size, organic matter and
calcium carbonate content in the bottom sediment and with physicochemical
parameters of the bottom water. The grain size decreases toward the mouth of the
estuary, whereas the organic matter and carbonate content increase. The salinity
increases significantly at 3.5 km upstream from the mouth, where there is also a
notable increase in fine sediments; the same site is the mean position of the
salinity front. The temperature and pH increase in the same direction. The Pinorg
total ranges between 3.18 and 7.13 umol g(-1), increasing toward the mouth. The
same trend is observed for the other phosphorus fractions P-Ca, P-Fe and P-f.a.,
which range from 0.68 to 1.91, 0.79 to 1.71 and 0.03 to 0.93 umol g(-1),
respectively. The P-Ca and P-Fe fractions are the most representative in the
Pinorg-total, occurring at 26.3 and 26.0 %, respectively.
PMID- 27610326
TI - An efficient reversible privacy-preserving data mining technology over data
streams.
AB - With the popularity of smart handheld devices and the emergence of cloud
computing, users and companies can save various data, which may contain private
data, to the cloud. Topics relating to data security have therefore received much
attention. This study focuses on data stream environments and uses the concept of
a sliding window to design a reversible privacy-preserving technology to process
continuous data in real time, known as a continuous reversible privacy-preserving
(CRP) algorithm. Data with CRP algorithm protection can be accurately recovered
through a data recovery process. In addition, by using an embedded watermark, the
integrity of the data can be verified. The results from the experiments show
that, compared to existing algorithms, CRP is better at preserving knowledge and
is more effective in terms of reducing information loss and privacy disclosure
risk. In addition, it takes far less time for CRP to process continuous data than
existing algorithms. As a result, CRP is confirmed as suitable for data stream
environments and fulfills the requirements of being lightweight and energy
efficient for smart handheld devices.
PMID- 27610329
TI - Epidemiological and cost analysis of burn injuries admitted to the emergency
department of a tertiary burn center.
AB - BACKGROUND: Burn injury is an emergency medical condition that rapidly develops
as a result of tissue exposure to electrical, chemical or thermal energy.
Therefore, its treatment usually begins at the emergency department. In this
study we aimed to perform an epidemiological analysis of burn injuries presenting
to the emergency department of a tertiary burn center, and factors affecting the
cost of their medical care. METHODS: Patients who presented to Baskent University
Ankara Hospital Adult Emergency Department with burn injuries between January
2012 and December 2014 were studied for age, sex, time of admission, type of burn
injury, clinical prognosis, mortality rate, percent burn area, and total cost of
care. A total of 264 patients were enrolled. Chi square test was used for the
comparison of categorical variables. Non-parametric tests were used for the
comparison of continuous variables. RESULTS: This study included 179 (67.8 %)
women and 85 (32.2 %) men. The most common types of burn injuries were hot water
burns and scalding. Eleven point seven percent of the patients sustained burn
injuries in occupational accidents. 95.1 % of the patients were discharged from
the emergency and 4.5 % of them were hospitalized. Only 1 (0.4 %) patient died.
There was no significant difference between patient outcomes (discharge vs.
hospital admission) with respect to the cost of care (p = 0.846) No significant
difference was found between the cost of care of surgical and non-surgical
management of burn injuries (p = 0.206). No significant difference was found
between the costs of care of different types of burn injuries (p = 0.053). There
was a significant difference between burn degrees with respect to the cost of
care (p = 0.038). A significant difference was found between the costs of care of
patients with a percent burn area of less than 10 % and those with a percent burn
area of more than 10 % (p < 0.001), indicating that as percent burn area
increased, a proportional increase occurred in the cost of care. CONCLUSIONS:
Burn degree and percent burn area were the main determinants of the cost of care
of burn injuries. In conclusion, burn injuries are preventable by taking
occupational measures and raising public awareness about domestic accidents.
PMID- 27610327
TI - The diversity of mtDNA rns introns among strains of Ophiostoma piliferum,
Ophiostoma pluriannulatum and related species.
AB - BACKGROUND: Based on previous studies, it was suspected that the mitochondrial
rns gene within the Ophiostomatales is rich in introns. This study focused on a
collection of strains representing Ophiostoma piliferum, Ophiostoma
pluriannulatum and related species that cause blue-stain; these fungi colonize
the sapwood of trees and impart a dark stain. This reduces the value of the
lumber. The goal was to examine the mtDNA rns intron landscape for these
important blue stain fungi in order to facilitate future annotation of
mitochondrial genomes (mtDNA) and to potentially identify mtDNA introns that can
encode homing endonucleases which may have applications in biotechnology.
RESULTS: Comparative sequence analysis identified five intron insertion sites
among the ophiostomatoid fungi examined. Positions mS379 and mS952 harbor group
II introns, the mS379 intron encodes a reverse transcriptase, and the mS952
intron encodes a potential homing endonuclease. Positions mS569, mS1224, and
mS1247 have group I introns inserted and these encode intact or eroded homing
endonuclease open reading frames (ORF). Phylogenetic analysis of the intron ORFs
showed that they can be found in the same insertion site in closely and distantly
related species. CONCLUSIONS: Based on the molecular markers examined (rDNA
internal transcribed spacers and rns introns), strains representing O. pilifera,
O. pluriannulatum and Ophiostoma novae-zelandiae could not be resolved.
Phylogenetic studies suggest that introns are gained and lost and that horizontal
transfer could explain the presence of related intron in distantly related fungi.
With regard to the mS379 group II intron, this study shows that mitochondrial
group II introns and their reverse transcriptases may also follow the life cycle
previously proposed for group I introns and their homing endonucleases. This
consists of intron invasion, decay of intron ORF, loss of intron, and possible
reinvasion.
PMID- 27610330
TI - Bacteriological quality evaluation of seawater and oysters from the Hansan
Geojeman area in Korea, 2011-2013: impact of inland pollution sources.
AB - From 2011 to 2013, we conducted a full sanitary survey of pollution sources in
proximity to a shellfish growing area in the Hansan-Geojeman region in Korea,
which includes a designated shellfish growing area. In the sea area, 1152
seawater and 209 oyster samples were collected and examined to evaluate their
bacteriological quality. There were 758 potential pollution sources in the
drainage area, including 40 sources discharging water in 2013. Fecal coliform
(FC) concentrations and impact radii of discharges ranged from 1.8 to 700,000
MPN/100 mL and from 3 to 600 m, respectively; however, the pollutants did not
reach the designated area. This demonstrates that the dilution of waste was
sufficient such that no significant impact occurred within the designated
shellfish growing area. The variation in the FC levels of seawater was closely
related to season and rainfall. The FC levels of seawater and oysters from the
designated area met the regulation limits set by various countries. No pathogens
were found in any oysters. The results of the survey indicate that the oysters
produced in this area are apparently safe for raw consumption based on their
bacterial quality.
PMID- 27610331
TI - Change in woody cover at representative sites in the Kruger National Park, South
Africa, based on historical imagery.
AB - BACKGROUND: The coexistence of woody vegetation and grass is a key characteristic
of savanna ecological balance. Gains in woody vegetation at the expense of grass
can lead to changes in grazer and browser carrying capacities on the savannas.
This study examined long-term change in woody cover at four study sites
representative of the geology and rainfall in the Kruger National Park, South
Africa. Scanned 1940/1942, 1968, and 1977 high spatial resolution (0.44-1.35 m)
panchromatic aerial photographs were used, supplemented by 5 and 10 m resolution
1998 and 2012 panchromatic and red band grey scale digital SPOT images. The
imagery datasets of the respective study sites were georeferenced to the UTM
projection. Woody cover on the imagery was enhanced using texture analysis, and
mapped by unsupervised classification of the texture images using the K-means
clustering algorithm. Change in woody cover was mapped using Boolean addition
Geographic Information System overlay analysis. RESULTS: The results indicated 29
and 40 % reductions in woody cover for the southern granites and southern basalts
sites, respectively. The northern granites and northern basalts sites, on the
other hand, had gains in woody cover over the analysis period. The location
context-specific factors of fire frequency and elephant density, and not rainfall
fluctuations, explained most of the change in woody cover. CONCLUSIONS: The
results point to the need for location context-specific management of fire and
elephant concentrations. The changes in woody cover are likely to have effects on
the grazer and browser carrying capacities of the savannas in the Kruger National
Park.
PMID- 27610328
TI - Big data and tactical analysis in elite soccer: future challenges and
opportunities for sports science.
AB - Until recently tactical analysis in elite soccer were based on observational data
using variables which discard most contextual information. Analyses of team
tactics require however detailed data from various sources including technical
skill, individual physiological performance, and team formations among others to
represent the complex processes underlying team tactical behavior. Accordingly,
little is known about how these different factors influence team tactical
behavior in elite soccer. In parts, this has also been due to the lack of
available data. Increasingly however, detailed game logs obtained through next
generation tracking technologies in addition to physiological training data
collected through novel miniature sensor technologies have become available for
research. This leads however to the opposite problem where the shear amount of
data becomes an obstacle in itself as methodological guidelines as well as
theoretical modelling of tactical decision making in team sports is lacking. The
present paper discusses how big data and modern machine learning technologies may
help to address these issues and aid in developing a theoretical model for
tactical decision making in team sports. As experience from medical applications
show, significant organizational obstacles regarding data governance and access
to technologies must be overcome first. The present work discusses these issues
with respect to tactical analyses in elite soccer and propose a technological
stack which aims to introduce big data technologies into elite soccer research.
The proposed approach could also serve as a guideline for other sports science
domains as increasing data size is becoming a wide-spread phenomenon.
PMID- 27610332
TI - Impact of cold atmospheric pressure argon plasma on antibiotic sensitivity of
methicillin-resistant Staphylococcus aureus strains in vitro.
AB - AIM: The antimicrobial activity of cold atmospheric pressure plasma (CAP), also
called tissue tolerable plasma (TTP), could be a promising option to eradicate
methicillin-sensitive as well as methicillin-resistant Staphylococcus aureus
strains, which often colonize chronic wounds. Currently, the influence of CAP on
the susceptibility of S. aureus to antibiotics is scarcely known, but could be
important for treatment of wounds. Therefore, the aim of this study was to
investigate whether CAP has an impact on the susceptibility of different S.
aureus strains to different antibiotics. METHOD: For assessment, the agar
diffusion test with different antibiotic test disks (cefuroxime, gentamicin,
oxacillin, vancomycin, ciprofloxacin, co-trimoxazole, clindamycin, erythromycin)
was used. Test strains were spread on agar plates and CAP treated before the
antibiotic disks were placed. After 24 hours cultivation, the inhibited growth
zones were measured and differences statistically evaluated. RESULTS: In most
cases, CAP had a negligible influence on the susceptibility to antibiotics. For
two strains, the susceptibility significantly decreased to beta-lactam
antibiotics. CONCLUSION: Because CAP can influence the antibiotic susceptibility
of S. aureus, before conducting combined treatment with local plasma application
on wounds and systemic antibiotics, their interaction must be analysed in vitro
to exclude unwanted combination effects.
PMID- 27610333
TI - Generating Light from Upper Excited Triplet States: A Contribution to the
Indirect Singlet Yield of a Polymer OLED, Helping to Exceed the 25% Singlet
Exciton Limit.
AB - The mechanisms by which light is generated in an organic light emitting diode
have slowly been elucidated over the last ten years. The role of triplet
annihilation has demonstrated how the "spin statistical limit" can be surpassed,
but it cannot account for all light produced in the most efficient devices. Here,
a further mechanism is demonstrated by which upper excited triplet states can
also contribute to indirect singlet production and delayed fluorescence. Since in
a device the population of these TN states is large, this indirect radiative
decay channel can contribute a sizeable fraction of the total emission measured
from a device. The role of intra- and interchain charge transfer states is
critical in underpinning this mechanism.
PMID- 27610335
TI - High Performance Field Emitters.
AB - The field electron emission performance of bulk, 1D, and 2D nanomaterials is here
empirically compared in the largest metal-analysis of its type. No clear trends
are noted between the turn-on electric field and maximum current density as a
function of emitter work function, while a more pronounced correlation with the
emitters dimensionality is noted. The turn-on field is found to be twice as large
for bulk materials compared to 1D and 2D materials, empirically confirming the
wider communities view that high aspect ratios, and highly perturbed surface
morphologies allow for enhanced field electron emitters.
PMID- 27610334
TI - Quantifying Bulk Electrode Strain and Material Displacement within Lithium
Batteries via High-Speed Operando Tomography and Digital Volume Correlation.
AB - Tracking the dynamic morphology of active materials during operation of lithium
batteries is essential for identifying causes of performance loss. Digital volume
correlation (DVC) is applied to high-speed operando synchrotron X-ray computed
tomography of a commercial Li/MnO2 primary battery during discharge. Real-time
electrode material displacement is captured in 3D allowing degradation mechanisms
such as delamination of the electrode from the current collector and electrode
crack formation to be identified. Continuum DVC of consecutive images during
discharge is used to quantify local displacements and strains in 3D throughout
discharge, facilitating tracking of the progression of swelling due to lithiation
within the electrode material in a commercial, spiral-wound battery during normal
operation. Displacement of the rigid current collector and cell materials
contribute to severe electrode detachment and crack formation during discharge,
which is monitored by a separate DVC approach. Use of time-lapse X-ray computed
tomography coupled with DVC is thus demonstrated as an effective diagnostic
technique to identify causes of performance loss within commercial lithium
batteries; this novel approach is expected to guide the development of more
effective commercial cell designs.
PMID- 27610336
TI - "Age" in lung transplantation: factors related to outcomes and other
considerations.
AB - The age of lung transplant recipients is steadily increasing. Older donors are
more frequently considered. The risk factors associated with advanced age in lung
transplantation warrant discussion to ensure optimal outcomes in this complex
endeavor. This report provides a summary of the pertinent topics and available
evidence.
PMID- 27610337
TI - Constancy and Change in the Prevalence and Frequency of Offending When Based on
Longitudinal Self-reports or Official Records: Comparisons by Gender, Race, and
Crime Type.
AB - INTRODUCTION: The study examines age-crime prevalence and age-crime frequency
curves based on longitudinal data from boys in the Pittsburgh Youth Study and
girls in the Pittsburgh Girls Study. RESULTS: Results show that the prevalence of
the age-crime curve for theft and violence (based on self-reports or police
charges) followed the typical age-crime curve for males and slightly less
distinctly for females, with the peak of offending occurring earlier for self
reports than for police charges. The decrease in police charges for violence and
theft took place at an earlier age for females than males, but this was not
distinct when self-reported delinquency was the criterion. The mean frequency of
self-reported theft and violence followed the age-crime curve for males but not
for females, who showed a mean frequency of offending which was more constant. In
contrast, the mean frequency of police charges increased with age for males and
females. Comparing African-American and Caucasian males and females shows a
higher prevalence but not a higher mean frequency of self-reported offending.
CONCLUSIONS: The results are reviewed in the light of other studies, and the
policy implications of the findings are discussed.
PMID- 27610338
TI - Reducing childhood obesity through coordinated care: Development of a park
prescription program.
AB - Major hindrances to controlling the current childhood obesity epidemic include
access to prevention and/or treatment programs that are affordable, provide
minimal barriers for participation, and are available to the general public.
Moreover, successful childhood obesity prevention efforts will require
coordinated partnerships in multiple sectors such as government, health care,
school/afterschool, and the community but very few documented sustainable
programs currently exist. Effective, community-based health and wellness programs
with a focus on maintaining healthy weight via physical activity and healthy
eating have the potential to be a powerful referral resource for pediatricians
and other healthcare professionals who have young patients who are
overweight/obese. The Miami Dade County Department of Parks, Recreation and Open
Spaces in partnership with the University of Miami UHealth Systems have created a
"Park Prescription Program (Parks Rx 4Health(TM))" that formally coordinates
pediatricians, families, parents, caregivers, and child/adolescents to provide
daily obesity-prevention activities. This Parks Rx 4Health(TM) program that we
describe here allows UHealth pediatricians to seamlessly refer their overweight
and obese patients to Fit2Play(TM), an evidence-based, park-based afterschool
health and wellness program. Measurable outcomes that include body mass index,
blood pressure, fitness, and nutrition knowledge are being collected at baseline
and at 3-and 6-mo after referral to document patient progress. Results are then
shared with the referring physician so they can follow up with the patient if
necessary. Identifying successful models that integrate primary care, public
health, and community-based efforts is important to accelerating progress in
preventing childhood obesity. Effective, community-based health and wellness
programs with a focus on physical activity and nutrition education could be a
powerful referral resource for pediatricians who have obese patients.
PMID- 27610339
TI - Transitioning antimicrobials from intravenous to oral in pediatric acute
uncomplicated osteomyelitis.
AB - Osteomyelitis is a bone infection that requires prolonged antibiotic treatment
and potential surgical intervention. If left untreated, acute osteomyelitis can
lead to chronic osteomyelitis and overwhelming sepsis. Early treatment is
necessary to prevent complications, and the standard of care is progressing to a
shorter duration of intravenous (IV) antibiotics and transitioning to oral
therapy for the rest of the treatment course. We systematically reviewed the
current literature on pediatric patients with acute osteomyelitis to determine
when and how to transition to oral antibiotics from a short IV course. Studies
have shown that switching to oral after a short course (i.e., 3-7 d) of IV
therapy has similar cure rates to continuing long-term IV therapy. Prolonged IV
use is also associated with increased risk of complications. Parameters that help
guide clinicians on making the switch include a downward trend in fever,
improvement in local tenderness, and a normalization in C-reactive protein
concentration. Based on the available literature, we recommend transitioning
antibiotics to oral after 3-7 d of IV therapy for pediatric patients (except
neonates) with acute uncomplicated osteomyelitis if there are signs of clinical
improvement, and such regimen should be continued for a total antibiotic duration
of four to six weeks.
PMID- 27610342
TI - History of the infantile hepatic hemangioma: From imaging to generating a
differential diagnosis.
AB - We aim to provide an up-to-date summary of infantile hepatic hemangioma (IHH) and
its misnomers and to dialectically present the differential diagnosis of these
rare entities of the liver. Eligible peer-reviewed articles on hepatic infantile
hemangiomas, published between 2000 and 2015, were reviewed for this study. IHH
is the most common hepatic vascular tumor in children. Once a liver mass is
identified in an infant, the differential diagnosis ranges from vascular
malformations to benign and malignant tumors including mesenchymal hamartoma,
hepatoblastoma, metastatic neuroblastoma, so careful physical examination,
imaging studies, and, if indicated, tumor markers and biopsy, are of pivotal
importance to ascertain the correct diagnosis. Despite the benign nature of IHHs,
some of these lesions may demand medical and/or surgical intervention, especially
for multiple and diffuse IHH. Complications can include hepatomegaly,
hypothyroidism and cardiac failure. Therefore, a close follow-up is required
until complete involution of the lesions. We propose an algorithm to guide the
physicians towards the proper management of hepatic lesions.
PMID- 27610341
TI - Spectrum of intracranial incidental findings on pediatric brain magnetic
resonance imaging: What clinician should know?
AB - Intracranial incidental findings on magnetic resonance imaging (MRI) of the brain
continue to generate interest in healthy control, research, and clinical
subjects. However, in clinical practice, the discovery of incidental findings
acts as a "distractor". This review is based on existing heterogeneous reports,
their clinical implications, and how the results of incidental findings influence
clinical management. This draws attention to the followings: (1) the prevalence
of clinically significant incidental findings is low; (2) there is a lack of a
systematic approach to classification; and discusses (3) how to deal with the
detected incidental findings based a proposed common clinical profile.
Individualized neurological care requires an active discussion regarding the need
for neuroimaging. Clinical significance of incidental findings should be decided
based on lesion's neuroradiologic characteristics in the given clinical context.
Available evidence suggests that the outcome of an incidentally found "serious
lesion in children" is excellent. Future studies of intracranial incidental
findings on pediatric brain MRI should be focused on a homogeneous population.
The study should address this clinical knowledge based review powered by the
statistical analyses.
PMID- 27610340
TI - Critical evaluation of unscientific arguments disparaging affirmative infant male
circumcision policy.
AB - We evaluate recent claims opposing infant male circumcision, a procedure now
supported by the evidence-based policy of the American Academy of Pediatrics. We
find those criticisms depend on speculative claims about the foreskin and
obfuscation of the strong scientific evidence supporting pediatric policy
development. An argument that circumcision should be delayed to allow a boy to
make up his own mind as an adult fails to appreciate the psychological,
scheduling and financial burdens later circumcision entails, so reducing the
likelihood that it will occur. In contrast, early infant circumcision is
convenient, safer, quicker, lower risk, healing is faster, cosmetic outcome is
routinely good and the lifetime benefits accrue immediately. Benefits include
reduction in urinary tract infections, inflammatory skin conditions, foreskin
problems, and, when older, substantial protection against sexually transmitted
infections and genital cancers in the male and his female sexual partners. Some
authorities regard the failure to offer parents early infant circumcision as
unethical, just as it would be unethical to fail to encourage the vaccination of
children. In conclusion, the criticisms of evidence-based infant male
circumcision policy are seriously flawed and should be dismissed as unhelpful to
evidence-based development and implementation of pediatric policy intended to
improve public health and individual wellbeing.
PMID- 27610343
TI - Drug delivery interfaces: A way to optimize inhalation therapy in spontaneously
breathing children.
AB - There are several different types of drug delivery interfaces available on the
market. Using the right interface for aerosol drug delivery to children is
essential for effective inhalation therapy. However, clinicians usually focus on
selecting the right drug-device combination and often overlook the importance of
interface selection that lead to suboptimal drug delivery and therapeutic
response in neonates and pediatrics. Therefore, it is necessary to critically
assess each interface and understand its advantage and disadvantages in aerosol
drug delivery to this patient population. The purpose of this paper is to provide
a critical assessment of drug delivery interfaces used for the treatment of
children with pulmonary diseases by emphasizing advantages and problems
associated with their use during inhalation therapy.
PMID- 27610344
TI - Skin disease and thyroid autoimmunity in atopic South Italian children.
AB - AIM: To verify the prevalence of thyroid autoimmunity (TA) and the possible
association between atopy and TA in children affected by skin disease. METHODS:
Three hundred and twenty-four children consecutively referred due to skin disease
symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven
were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with
chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up
for atopy, the children were divided into two groups: Atopics and non-atopics. TA
was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin
autoantibodies levels more than twice normal values over a period of two months
by immunoassay. RESULTS: In all children with skin disease, a significant
prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P =
0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI:
1.71-19.35) were observed. These findings were confirmed as significant in
children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P =
0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a
significantly higher prevalence of TA (26.9%), but none of the non-atopics showed
CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2)
prevalence of TA, compared with none of the non-atopics. CONCLUSION: In children
with skin disease, atopy seems to be associated with an increased risk of TA.
PMID- 27610346
TI - Prevalence of recent immunisation in children with febrile convulsions.
AB - AIM: To determine the prevalence of recent immunisation amongst children under 7
years of age presenting for febrile convulsions. METHODS: This is a retrospective
study of all children under the age of seven presenting with febrile convulsions
to a tertiary referral hospital in Sydney. A total of 78 cases occurred in the
period January 2011 to July 2012 and were included in the study. Data was
extracted from medical records to provide a retrospective review of the
convulsions. RESULTS: Of the 78 total cases, there were five medical records
which contained information on whether or not immunisation had been administered
in the preceding 48 h to presentation to the emergency department. Of these five
patients only one patient (1.28% of the study population) was confirmed to have
received a vaccination with Infanrix, Prevnar and Rotavirus. The majority of
cases reported a current infection as a likely precipitant to the febrile
convulsion. CONCLUSION: This study found a very low prevalence of recent
immunisation amongst children with febrile convulsions presenting to an emergency
department at a tertiary referral hospital in Sydney. This finding, however, may
have been distorted by underreporting of vaccination history.
PMID- 27610345
TI - Effects of resistance training on cardiovascular health in non-obese active
adolescents.
AB - AIM: To determine the benefits of a 10-wk resistance training programme on
cardiovascular health in non-obese and active adolescents. METHODS: This is a
pragmatic randomised controlled intervention. The study was carried out in a Hong
Kong Government secondary school. Thirty-eight lean and active boys and girls
were randomised to either the resistance training group or the control group.
Students in the resistance training group received in-school 10-wk supervised
resistance training twice per week, with each session lasting 70 min. Main
outcome measures taken before and after training included brachial endothelial
dependent flow-mediated dilation, body composition, fasting serum lipids, fasting
glucose and insulin, high sensitive C-reactive protein, 24-h ambulatory blood
pressure and aerobic fitness. RESULTS: The only training related change was in
endothelial dependent flow-mediated dilation which increased from 8.5% to 9.8%. A
main effect of time and an interaction (P < 0.005) indicated that this
improvement was a result of the 10-wk resistance training. Main effects for time
(P < 0.05) in a number of anthropometric, metabolic and vascular variables were
noted; however, there were no significant interactions indicating the change was
more likely an outcome of normal growth and development as opposed to a training
effect. CONCLUSION: Ten weeks of resistance training in school appears to have
some vascular benefit in active, lean children.
PMID- 27610347
TI - Subclinical hypothyroidism in atopic South Italian children.
AB - AIM: To verify if subclinical hypothyroidism (SCH) could be associated to atopy
in children. METHODS: Seven hundred and thirty-two Caucasian children from South
Italy presenting symptoms of allergic disease were enrolled and submitted to
atopy, obesity, chronic low grade inflammation, and SCH work up. RESULTS: Four
hundred and forty-five out of 705 (63.12%) children affected by allergic disease
were diagnosed as atopic and 260 (36.88%) as not atopic. The SCH prevalence was
6.3%. Significant higher prevalence of SCH among atopic children with average
(group 2) and high (group 3) low grade chronic inflammation compared to atopic
children with mild (group 1) low grade chronic inflammation was present.
Moreover, group 1 and group 2 presented an OR to show SCH of 2.57 (95%CI: 1.55
6.26) and 2.96 (95%CI: 1.01-8.65), respectively. Both in atopic and not atopic
children we found C3 serum levels significantly higher in group 3 respect to
group 2 and group 1. Noteworthy, among atopic patients, also total immunoglobulin
E (IgE) serum levels, were significantly higher in group 3 compared to group 2
and group 1 children. In atopic children, C3 and total IgE serum values increased
in parallel with the increase of C-reactive protein values, while in not atopic
children this phenomenon was not evident. CONCLUSION: The possibility exists that
an increasing atopic inflammation contributes to SCH occurrence. So far this is
the first report in literature showing an association between SCH and atopy but
further studies are needed to confirm our data.
PMID- 27610348
TI - Potential carrier priming effect in Australian infants after 7-valent
pneumococcal conjugate vaccine introduction.
AB - AIM: To investigate evidence of clinical protection in infants after one dose of
7-valent pneumococcal conjugate vaccine (7vPCV) owing to carrier priming.
METHODS: Using Australian National Notifiable Diseases Surveillance System data,
we conducted a descriptive analysis of cases of vaccine type invasive
pneumococcal disease (VT-IPD) during "catch-up" years, when 7vPCV was carrier
primed by prior administration of DTPa vaccine. We compared the number of VT-IPD
cases occurring 2-9 wk after a single dose of 7vPCV (carrier primed), with those
< 2 wk post vaccination, when no protection from 7vPCV was expected yet. Further
comparison was conducted to compare the occurrence of VT-IPD cases vs non-VT-IPD
cases after a single carrier-primed dose of 7vPCV. RESULTS: We found four VT-IPD
cases occurring < 2 wk after one carrier primed dose of 7vPCV while only one case
occurred 2-9 wk later. Upon further comparison with the non-VT-IPD cases that
occurred after one carrier primed dose of 7vPCV, two cases were detected within 2
wk, whereas seven occurred within 2-9 wk later; suggesting a substantial level of
protection from VT-IPD occurring from 2 wk after carrier-primed dose of 7vPCV.
CONCLUSION: This data suggest that infants may benefit from just one dose of
7vPCV, likely through enhanced immunity from carrier priming effect. If this is
proven, an adjusted 2-dose schedule (where the first dose of PCV is not given
until after DTPa) may be sufficient and more cost-effective.
PMID- 27610349
TI - Single institution experience with the Ladd's procedure in patients with
heterotaxy and stage I palliated single-ventricle.
AB - AIM: To investigate and describe our current institutional management protocol
for single-ventricle patients who must undergo a Ladd's procedure. METHODS: We
retrospectively reviewed the charts of all patients from January 2005 to March
2014 who were diagnosed with heterotaxy syndrome and an associated intestinal
rotation anomaly who carried a cardiac diagnosis of functional single ventricle
and were status post stage I palliation. A total of 8 patients with a history of
stage I single-ventricle palliation underwent Ladd's procedure during this time
period. We reviewed each patients chart to determine if significant
intraoperative or post-operative morbidity or mortality occurred. We also
described our protocolized management of these patients in the cardiac intensive
care unit, which included pre-operative labs, echocardiography, milrinone
infusion, as well as protocolized fluid administration and anticoagulation
regimines. We also reviewed the literature to determine the reported morbidity
and mortality associated with the Ladd's procedure in this particular cardiac
physiology and if other institutions have reported protocolized care of these
patients. RESULTS: A total of 8 patients were identified to have heterotaxy with
an intestinal rotation anomaly and single-ventricle heart disease that was status
post single ventricle palliation. Six of these patients were palliated with a
Blaylock-Taussig shunt, one of whom underwent a Norwood procedure. The two other
patients were palliated with a stent, which was placed in the ductus arteriosus.
These eight patients all underwent elective Ladd's procedure at the time of
gastrostomy tube placement. Per our protocol, all patients remained on aspirin
prior to surgery and had no period where they were without anticoagulation. All
patients remained on milrinone during and after the procedure and received fluid
administration upon arrival to the cardiac intensive care unit to account for
losses. All 8 patients experienced no intraoperative or post-operative
complications. All patients survived to discharge. One patient presented to the
emergency room two months after discharge in cardiac arrest and died due to bowel
obstruction and perforation. CONCLUSION: Protocolized intensive care management
may have contributed to favorable outcomes following Ladd's procedure at our
institution.
PMID- 27610350
TI - Significant variations in nutritional supplementation amongst neonates in the
United Kingdom.
AB - AIM: To ascertain United Kingdom adherence to European society of Paediatric
Gastroenterology, Hepatology and Nutrition guidance (ESPGHAN). METHODS: A
national cross sectional questionnaire study of neonatal units across England was
completed between January and March 2014. All 174 units in the country were
attempted to be contacted to complete a telephone survey. This included all level
1, 2 and 3 units. They were initially contacted by phone and asking any senior
member of the team about their current practice and procedures. The first ten
telephone interviews were completed with two researchers present to ensure
consistency of approach. If no response was received or no details were
available, one further attempt was made to contact the unit. The results were
recorded in a proforma and then collated and entered into a spreadsheet for
analysis. Comparison to United Kingdom adherence to ESPGHAN guidance was
completed. RESULTS: Response rate was 53%. There was variation in use of all
supplements. The survey collected data from 91 neonatal units (53% response
rate). It was found that 10% of neonatal units had no fixed policy on
supplements. The protocols regarding supplementation involved predominantly folic
acid, vitamin A, vitamin D and iron, with much variation in doses and regimens.
The criteria for prescribing supplements was largely based on age (47%) with only
7% using a weight targets to initiate supplements. Summary data regarding the
appropriateness of each nutritional supplement for a variety of different weights
are presented, as well as comparison to ESPGHAN guidance which suggests issues
with both underdoing of Breast Fed infants and overdosing of infants on several
artificial formulas which already contain significant amounts of these
nutritional elements. CONCLUSION: There is significant heterogeneity in neonatal
policies when prescribing supplements to neonates. National policies which take
international guidance into account are recommended.
PMID- 27610352
TI - Solitary rectal ulcer syndrome: Is it really a rare condition in children?
AB - AIM: To evaluate the clinicopathologic characteristics of the children with
solitary rectal ulcer. METHODS: Fifty-five children with a confirmed diagnosis of
solitary rectal ulcer were studied in a period of 11 years from March 2003 to
March 2014. All data were collected from the patients, their parents and medical
records in the hospital. RESULTS: From 55 studied patients, 41 were male (74.5%)
and 14 female (25.5%). The mean age of the patients was 10.4 +/- 3.7 years and
the average time period from the beginning of symptoms to diagnosis of solitary
rectal ulcer was 15.5 +/- 11.2 mo. The most common clinical symptoms in our
patients were rectal bleeding (n = 54, 98.2%) and straining during defecation or
forceful defecation (n = 50, 90.9%). Other symptoms were as follows respectively:
Sense of incomplete evacuation (n = 34, 61.8%), mucorrhea (n = 29, 52.7%),
constipation (n = 14, 25.4%), tenesmus and cramping (n = 10, 18.2%), diarrhea (n
= 9, 16.4%), and rectal pain (n = 5, 9.1%). The colonoscopic examination revealed
67.3% ulcer, 12.7% polypoid lesions, 10.9% erythema, 7.3% both polypoid lesions
and ulcer, and 1.8% normal. Most of the lesions were in the rectosigmoid area at
a distance of 4-6 cm from the anal margin. Finally, 69.8% of the patients
recovered successfully with conservative, medical and surgical management.
CONCLUSION: The study revealed that solitary rectal ulcer is not so uncommon
despite what was seen in previous studies. As the most common symptom was rectal
bleeding, clinicians and pathologists should be familiar with this disorder and
common symptoms in order to prevent its complications with early diagnosis.
PMID- 27610351
TI - Hypothesis on supine sleep, sudden infant death syndrome reduction and
association with increasing autism incidence.
AB - AIM: To identify a hypothesis on: Supine sleep, sudden infant death syndrome
(SIDS) reduction and association with increasing autism incidence. METHODS:
Literature was searched for autism spectrum disorder incidence time trends, with
correlation of change-points matching supine sleep campaigns. A mechanistic model
expanding the hypothesis was constructed based on further review of
epidemiological and other literature on autism. RESULTS: In five countries
(Denmark, United Kingdom, Australia, Israel, United States) with published time
trends of autism, change-points coinciding with supine sleep campaigns were
identified. The model proposes that supine sleep does not directly cause autism,
but increases the likelihood of expression of a subset of autistic criteria in
individuals with genetic susceptibility, thereby specifically increasing the
incidence of autism without intellectual disability. CONCLUSION: Supine sleep is
likely a physiological stressor, that does reduce SIDS, but at the cost of impact
on emotional and social development in the population, a portion of which will be
susceptible to, and consequently express autism. A re-evaluation of all benefits
and harms of supine sleep is warranted. If the SIDS mechanism proposed and autism
model presented can be verified, the research agenda may be better directed, in
order to further decrease SIDS, and reduce autism incidence.
PMID- 27610353
TI - Factors affecting breastfeeding duration in Greece: What is important?
AB - AIM: To investigate factors associated with breastfeeding duration (BD) in a
sample of mothers living in Greece. METHODS: Four hundred and twenty-eight
mothers (438 infants) were initially recruited in a tertiary University Hospital.
Monthly telephone interviews (1665 in total) using a structured questionnaire
(one for each infant) were conducted until the sixth postpartum month. Cox
regression analysis was used to assess factors influencing any BD. RESULTS: Any
breastfeeding rates in the first, third, and sixth month of the infant's life
reached 87.5%, 57.0% and 38.75%, respectively. In the multivariate analysis,
maternal smoking in the lactation period [hazard-ratio (HR) = 4.20] and
psychological status (HR = 1.72), and the introduction of a pacifier (HR = 2.08),
were inversely associated, while higher maternal education (HRuniversity/college
vs primary/high school = 0.53, HRmaster's vs primary/high school = 0.20), and
being an immigrant (HR = 0.35) were positively associated with BD. CONCLUSION:
Public health interventions should focus on campaigns against smoking during
lactation, target women of lower educational status, and endorse the delayed
introduction of pacifiers.
PMID- 27610354
TI - LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk
Endometrial Cancer.
AB - INTRODUCTION: A 51 year-old woman was diagnosed with endometrial cancer (EC) and
underwent surgical staging. Pathological evaluation showed a 2 cm * 1 cm G2
endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient
was classified as low risk of recurrence, and no adjuvant treatment was offered.
Six months after surgery, the patient developed an early vescico-vaginal
recurrence, and chemotherapy treatment was started. Few months later, a
subsequent involvement of vaginal wall, ileum, and omentum was detected, and the
patient underwent second surgery. BACKGROUND: LH/hCG-receptor (LH/hCG-R)
expression has been previously reported to be associated with an invasive
phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a
prometastatic molecular device. DISCUSSION: We analyzed the expression level of
LH/hCG-R in cancer specimens collected during surgeries. Molecular and
immunohistochemical analyses showed a strong expression of both mRNA and protein
for LH/hCG-R in all specimens. CONCLUSION: LH/hCG-R expression may be assessed
together with other clinicopathological parameters in order to better predict the
risk of recurrence in low-risk EC patients. Further clinical trials are warranted
in order to validate LH/hCG-R as biomarker in EC.
PMID- 27610355
TI - Economic Game Theory to Model the Attenuation of Virulence of an Obligate
Intracellular Bacterium.
AB - Diseases induced by obligate intracellular pathogens have a large burden on
global human and animal health. Understanding the factors involved in the
virulence and fitness of these pathogens contributes to the development of
control strategies against these diseases. Based on biological observations, a
theoretical model using game theory is proposed to explain how obligate
intracellular bacteria interact with their host. The equilibrium in such a game
shows that the virulence and fitness of the bacterium is host-triggered and by
changing the host's defense system to which the bacterium is confronted, an
evolutionary process leads to an attenuated strain. Although, the attenuation
procedure has already been conducted in practice in order to develop an
attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of
understanding of the theoretical basis behind this process. Our work provides a
model to better comprehend the existence of different phenotypes and some
underlying evolutionary mechanisms for the virulence of obligate intracellular
bacteria.
PMID- 27610356
TI - Quality of reporting randomized controlled trials (RCTs) in diabetes in Iran; a
systematic review.
AB - OBJECTIVE: To determine the quality of randomized controlled clinical trial (RCT)
reports in diabetes research in Iran. DESIGN: Systematized review. METHODS: We
included RCTs conducted on diabetes mellitus in Iran. Animal studies, educational
interventions, and non-randomized trials were excluded. We excluded duplicated
publications reporting the same groups of participants and intervention. Two
independent reviewers identify all eligible articles specifically designed data
extraction form. We searched through international databases; Scopus, ProQuest,
EBSCO, Science Direct, Web of Science, Cochrane Library, PubMed; and national
databases (In Persian language) such as Magiran, Scientific Information Database
(SID) and IranMedex from January 1995 to January of 2013 Two investigators
assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of
Reporting Trials) checklist statemen.t,. Discrepancies were resolved by third
reviewer consulting. RESULTS: One hundred and eight five (185) studies were
included and appraised. Half of them (55.7 %) were published in Iranian journals.
Most (89.7 %) were parallel RCTs, and being performed on type2 diabetic patients
(77.8 %). Less than half of the CONSORT items (43.2 %) were reported in studies,
totally. The reporting of randomization and blinding were poor. A few studies
15.1 % mentioned the method of random sequence generation and strategy of
allocation concealment. And only 34.8 % of trials report how blinding was
applied. CONCLUSIONS: The findings of this study show that the quality of RCTs
conducted in Iran in diabetes research seems suboptimal and the reporting is also
incomplete however an increasing trend of improvement can be seen over time.
Therefore, it is suggested Iranian researchers pay much more attention to design
and methodological quality in conducting and reporting of diabetes RCTs.
PMID- 27610357
TI - Eosinophilic Esophagitis in Children and Adolescents with Abdominal Pain:
Comparison with EoE-Dysphagia and Functional Abdominal Pain.
AB - Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and
outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD,
histology, symptom scores, and treatments were recorded for the three groups.
Cluster analysis was done. Results. Dysphagia and abdominal pain were different
in numbers but not statistically significant between EoE-AP and EoE-D. EGD,
linear furrows, white exudates were more in the EoE-D and both combined were
significant (p < 0.05). EoE-D, peak and mean eosinophils (p 0.06) and
eosinophilic micro abscesses (p 0.001) were higher. Follow-Up. Based on single
symptom, EoE-AP had 30% (p 0.25) improvement, EoE-D 86% (p < 0.001) and similar
with composite score (p 0.57 and <0.001, resp.). Patients who had follow-up,
EGD: 42.8% with EoE-AP and 77.8% with EoE-D, showed single symptom improvement
and the eosinophil count fell from 38.5/34.6 (peak and mean) to 31.2/30.4 (p
0.70) and from 43.6/40.8 to 25.2/22.8 (p < 0.001), respectively. FAP-N patients
had similar symptom improvement like EoE-D. Cluster Analysis. EoE-AP and FAP-N
were similar in clinical features and response to treatment, but EoE-D was
distinctly different from EoE-AP and FAP-N. Conclusion. Our study demonstrates
that EoE-AP and EoE-D have different histology and outcomes. In addition, EoE-AP
has clinical features similar to the FAP-N group.
PMID- 27610358
TI - Use of Hypotonic Maintenance Intravenous Fluids and Hospital-Acquired
Hyponatremia Remain Common in Children Admitted to a General Pediatric Ward.
AB - AIM: To evaluate maintenance intravenous fluid-prescribing practices and the
incidence of hospital-acquired hyponatremia in children admitted to a general
pediatric ward. METHODS: This is a prospective observational study conducted over
a 2-month period in children ages 2 months to 5 years who were admitted to a
general pediatric ward and who were receiving maintenance intravenous fluids. The
composition, rate, and duration of intravenous fluids were chosen at the
discretion of the treating physician. Serum biochemistries were obtained at
baseline and 24 h following admission. Patients who were at high risk for
developing hyponatremia or hypernatremia or had underlying chronic diseases or
were receiving medications associated with a disorder in sodium and water
homeostasis were excluded. Intravenous fluid composition and the incidence of
hyponatremia (sodium <135 mEq/L) were assessed. RESULTS: Fifty-six children were
enrolled. All received hypotonic fluids; 87.5% received 0.18% sodium chloride
(NaCl) and 14.3% received 0.45% NaCl. Forty percent of patients (17/42) with a
serum sodium (SNa) less than 140 mEq/L experienced a fall in SNa with 12.5% of
all patients (7/56) developing hospital-acquired or aggravated hyponatremia (126
134 mEq/L) with fall in SNa between 2 and 10 mEq/L. CONCLUSION: Administration of
hypotonic fluids was a prevalent practice in children admitted to a general
pediatric ward and is associated with acute hospital-acquired hyponatremia.
PMID- 27610359
TI - Evaluating Research Impact: The Development of a Research for Impact Tool.
AB - INTRODUCTION: This paper examines the process of developing a Research for Impact
Tool in the contexts of general fiscal constraint, increased competition for
funding, perennial concerns about the over-researching of Aboriginal and Torres
Strait Islander issues without demonstrable benefits as well as conceptual and
methodological difficulties of evaluating research impact. The aim is to
highlight the challenges and opportunities involved in evaluating research impact
to serve as resource for potential users of the research for impact tool and
others interested in assessing the impact of research. MATERIALS AND METHODS: A
combination of literature reviews, workshops with researchers, and reflections by
project team members and partners using participatory snowball techniques.
RESULTS: Assessing research impact is perceived to be difficult, akin to the so
called "wicked problem," but not impossible. Heuristic and collaborative approach
to research that takes the expectations of research users, research participants
and the funders of research offers a pragmatic solution to evaluating research
impact. The logic of the proposed Research for Impact Tool is based on the
understanding that the value of research is to create evidence and/or products to
support smarter decisions so as to improve the human condition. Research is,
therefore, of limited value unless the evidence created is used to make smarter
decisions for the betterment of society. A practical way of approaching research
impact is, therefore, to start with the decisions confronting decision makers
whether they are government policymakers, industry, professional practitioners,
or households and the extent to which the research supports them to make smarter
policy and practice decisions and the knock-on consequences of doing so. Embedded
at each step in the impact planning and tracking process is the need for
appropriate mix of expertise, capacity enhancement, and collaborative
participatory learning-by-doing approaches. DISCUSSION: The tool was developed in
the context of Aboriginal and Torres Strait Islander research but the basic idea
that the way to assess research impact is to start upfront with the information
needs of decisions makers is equally applicable to research in other settings,
both applied (horizontal) and basic (vertical) research. The tool will be further
tested and evaluated with researchers over the next 2 years (2016/17). The
decision by the Australian Government to include 'industry engagement' and
'impact' as additions to the Excellence in Research for Australia (ERA) quality
measures from 2018 makes the Research for Impact Tool a timely development. The
wider challenge is to engage with major Australian research funding agencies to
ensure consistent alignment and approaches across research users, communities,
and funders in evaluating impact.
PMID- 27610360
TI - Editorial: Food, Nature, and Health: Dueling Epistemologies.
PMID- 27610361
TI - Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony
Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and
Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged
Swine.
AB - Salmonella colonization of food animals is a concern for animal health and public
health as a food safety risk. Various obstacles impede the effort to reduce
asymptomatic Salmonella carriage in food animals, including the existence of
numerous serovars and the ubiquitous nature of Salmonella. To develop an
intervention strategy that is non-specific yet effective against diverse
Salmonella serovars, we explored the prophylactic use of a cytokine to decrease
Salmonella in swine by boosting the host's innate immune system. Granulocyte
colony stimulating factor (G-CSF) is the major cytokine regulating the
production, differentiation, function, and survival of neutrophils. Neutrophils
play a critical role in the response to Salmonella; therefore, we evaluated the
vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in
pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a
replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF
(Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene
encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were
intranasally inoculated with 1 * 10(7) colony forming unit (CFU) of Salmonella
enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella,
Ad5-G-CSF-treated pigs shed significantly less Salmonella (~10(3) CFU/g) in their
feces than Ad5-empty-treated pigs (~10(4)-10(5) CFU/g; P < 0.05). A significant 4
log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated
pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the
Peyer's patch region of the ileum exhibited a significant 0.5-log reduction in
colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all
challenged pigs was assessed by sequencing and analyzing the V1-V3 region of the
16S rRNA gene from fecal DNA samples. The microbial community structure of
Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF
treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF
administration mitigated changes in the microbial community structure caused by
Salmonella challenge. Collectively, these data suggest that delivery of a
targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce
Salmonella colonization, potentially during periods of immunological stress.
PMID- 27610362
TI - Effect of Preventive Chlamydia abortus Vaccination in Offspring Development in
Sheep Challenged Experimentally.
AB - Ovine enzootic abortion, caused by Chlamydia abortus, leads to important economic
losses worldwide. In addition to reproductive failures, infection may impact lamb
growth during the first weeks after birth, yet this effect has not been well
characterized. Vaccination can help to control the disease but variable efficacy
values have been described, possibly related with factors associated with the
host, the vaccine, the parameter used for efficacy determination, and the
challenge conditions. In this context, we evaluated the efficacy of an
inactivated standard commercial vaccine and a 1/2 diluted dose in pregnant sheep
challenged with C. abortus by examining multiple indicators of vaccine effect
(including incidence of reproductive failures, bacterial excretion, and evolution
of weight gain of viable lambs during the first month of life). Three groups of
ewes [control non-vaccinated, C (n = 18); vaccinated with standard dose, SV (n =
16); and vaccinated with 1/2 dose, DV (n = 17)], were challenged approximately 90
days post-mating and tested using direct PCR (tissue samples and vaginal swabs)
and ELISA (serum) until 31 days post-reproductive outcome. There were not
significant differences in the proportions of reproductive failures or bacterial
shedding after birth/abortion regardless the vaccination protocol. However, a
beneficial effect of vaccination on offspring growth was detected in both
vaccinated groups compared with the controls, with a mean increase in weight
measured at 30 days of life of 1.5 and 2.5 kg (p = 0.056) and an increase in the
geometric mean of the daily gain of 8.4 and 9.7% in lambs born from DV and SV
ewes compared with controls, respectively. Our results demonstrate the effect of
an inactivated vaccine in the development of the offspring of C. abortus-infected
ewes at a standard and a diluted dose, an interesting finding given the
difficulty in achieving sufficient antigen concentration in the production of
enzootic abortion of ewes-commercial vaccines.
PMID- 27610363
TI - Histological and Molecular Characterization of Grape Early Ripening Bud Mutant.
AB - An early ripening bud mutant was analyzed based on the histological, SSR, and
methylation-sensitive amplified polymorphism (MSAP) analysis and a layer-specific
approach was used to investigate the differentiation between the bud mutant and
its parent. The results showed that the thickness of leaf spongy tissue of mutant
(MT) is larger than that of wild type (WT) and the differences are significant.
The mean size of cell layer L2 was increased in the mutant and the difference is
significant. The genetic background of bud mutant revealed by SSR analysis is
highly uniform to its parent; just the variations from VVS2 SSR marker were
detected in MT. The total methylation ratio of MT is lower than that of the
corresponding WT. The outside methylation ratio in MT is much less than that in
WT; the average inner methylation ratio in MT is larger than that in WT. The
early ripening bud mutant has certain proportion demethylation in cell layer L2.
All the results suggested that cell layer L2 of the early ripening bud mutant has
changed from the WT. This study provided the basis for a better understanding of
the characteristic features of the early ripening bud mutant in grape.
PMID- 27610364
TI - Genotype Distribution of Human Papillomavirus among Women with Cervical
Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence
Area of Esophageal Carcinoma in China.
AB - Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from
38,397 women with normal cytology, 1341 women with cervical cytology
abnormalities, and 223 women with ISCC were retrospectively evaluated by a
hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%,
and 96.86% in women with normal cytology, cervical cytology abnormalities, and
ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16
(1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most
prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58
(7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had
the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while
HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%,
41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common
types in women with ISCC. These data might contribute to increasing the knowledge
of HPV epidemiology and providing the guide for vaccine selection for women in
Shantou.
PMID- 27610365
TI - Optimization to the Culture Conditions for Phellinus Production with Regression
Analysis and Gene-Set Based Genetic Algorithm.
AB - Phellinus is a kind of fungus and is known as one of the elemental components in
drugs to avoid cancers. With the purpose of finding optimized culture conditions
for Phellinus production in the laboratory, plenty of experiments focusing on
single factor were operated and large scale of experimental data were generated.
In this work, we use the data collected from experiments for regression analysis,
and then a mathematical model of predicting Phellinus production is achieved.
Subsequently, a gene-set based genetic algorithm is developed to optimize the
values of parameters involved in culture conditions, including inoculum size, PH
value, initial liquid volume, temperature, seed age, fermentation time, and
rotation speed. These optimized values of the parameters have accordance with
biological experimental results, which indicate that our method has a good
predictability for culture conditions optimization.
PMID- 27610366
TI - Preparation and In Vivo Pharmacokinetics of the Tongshu Suppository.
AB - Astragalus polysaccharide (APS) (used for intestinal protection) was added to
formulate the Tongshu suppository to improve the pharmacokinetics of Aceclofenac,
which were assessed in New Zealand rabbits using an orthogonal experimental
design. The single-agent Aceclofenac was taken as the control formulation. The
concentration-time and drug release curves were drawn, and T max (min), C max
(MUg.mL(-1)), AUC0->infinity , and MRT were compared using a pharmacokinetic
systems program. The formulated Tongshu suppository had moderate hardness, a
smooth surface with uniform color, and theoretical drug-loading rate of 8%. Its
release rate was in accordance with the drug preparation requirements. The
concentration-time curves and drug release curves revealed that the maximum
concentrations (C max) were 4.18 +/- 1.03 MUg.mL(-1) and 3.34 +/- 0.41 MUg.mL(-1)
for the Tongshu and Aceclofenac suppositories, respectively, showing
statistically insignificant difference, while the peak times were 34.87 +/- 4.69
min and 34.76 +/- 6.34 min, respectively, also showing statistically
insignificant difference. Compared with the Aceclofenac suppository, the relative
bioavailability of the Tongshu suppository was 104.4%, and the difference between
them was statistically insignificant. In this experiment, the Tongshu suppository
was prepared using the hot-melt method. In vivo pharmacokinetic studies confirmed
it had higher bioavailability than the Aceclofenac suppository.
PMID- 27610368
TI - Safety, Efficiency, and Outcomes of Perineoplasty: Treatment of the Sensation of
a Wide Vagina.
AB - Background. The sensation of a wide vagina is a common problem for women after
childbirth. As its etiology is unknown, there is no uniform management strategy.
We hypothesized that, rather than vaginal laxity, the cause was level 3 pelvic
support deficiency. Methods. This retrospective study compared preoperative and
postoperative genital hiatus length, perineal length, and total vaginal length in
patients treated with perineoplasty for the sensation of a wide vagina. A
telephone survey was used to determine postoperative patient and male partner
satisfaction rates. Results. Mean age of patients was 48 (26-68) years; mean body
mass index (BMI) was 25.3 (17.6-33.2); and mean parity was 2.5 (2-5).
Preoperative and postoperative genital hiatus, perineal length, and total vaginal
length were 4.62 and 3.18 (p < 0.01), 3.06 and 4.04 (p < 0.01), and 9.43 and 9.43
(p = 0.882), respectively. At the 6-month follow-up, the success rate of the
perineoplasty procedure was 87.9%; according to a visual analog scale, partner
satisfaction rate was 92.6%. Ten percent (n = 4) of patients said they
experienced dyspareunia during sexual intercourse at the introitus of the vagina.
Conclusion. With low dyspareunia rates, low complication rates, high patient
satisfaction, and satisfactory anatomical success, perineoplasty can be
considered successful for treatment of the sensation of a wide vagina.
PMID- 27610367
TI - Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung
Adenocarcinoma.
AB - As smoking rates decrease, proportionally more cases with lung adenocarcinoma
occur in never-smokers, while aberrant DNA methylation has been suggested to
contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult
to distinguish which genes play key roles in tumorigenic processes via DNA
methylation-mediated gene silencing from a large number of differentially
methylated genes. By integrating gene expression and DNA methylation data, a
pipeline combined with the differential network analysis is designed to uncover
driver methylation genes and responsive modules, which demonstrate distinctive
expressions and network topology in tumors with aberrant DNA methylation.
Totally, 135 genes are recognized as candidate driver genes in early stage lung
adenocarcinoma and top ranked 30 genes are recognized as driver methylation
genes. Functional annotation and the differential network analysis indicate the
roles of identified driver genes in tumorigenesis, while literature study reveals
significant correlations of the top 30 genes with early stage lung adenocarcinoma
in never-smokers. The analysis pipeline can also be employed in identification of
driver epigenetic events for other cancers characterized by matched gene
expression data and DNA methylation data.
PMID- 27610369
TI - Clinical Application of Revised Laboratory Classification Criteria for
Antiphospholipid Antibody Syndrome: Is the Follow-Up Interval of 12 Weeks Instead
of 6 Weeks Significantly Useful?
AB - Background. According to revised classification criteria of true antiphospholipid
antibody syndrome, at least one of three antiphospholipid antibodies should be
present on two or more occasions at least 12 weeks apart. However, it can be
inconvenient to perform follow-up tests with interval of 12 weeks. We
investigated clinical application of follow-up tests with interval of 12 weeks.
Method. Totals of 67, 199, and 332 patients tested positive initially for the
lupus anticoagulants confirm, the anti-beta 2 glycoprotein-I antibody, and the
anti-cardiolipin antibody test, respectively, from Jan 2007 to Jul 2009. We
investigated clinical symptoms of patients, follow-up interval, and results of
each test. Results. Among patients with initial test positive, 1.5%-8.5% were
subjected to follow-up tests at interval of more than 12 weeks. Among 25 patients
with negative conversion in tests, patients with interval of more than 12 weeks
showed clinical symptom positivity of 33.3%, which was higher than that of 12.5%
with 6-12 weeks. Among 34 patients with persistent test positive, clinical
symptoms positivity trended to be more evident in patients at interval of 6-12
weeks (47.4% versus 26.7%, P = 0.191) than more than 12 weeks. Conclusion. Less
than 10% of patients with initial test positive had follow-up tests at interval
of more than 12 weeks and the patients with persistent test positive at interval
of more than 12 weeks showed trends toward having lower clinical symptoms than 6
12 weeks. More research is needed focused on the evidence that follow-up test at
interval of more than 12 weeks should be performed instead of 6 weeks.
PMID- 27610370
TI - Corrigendum to "Calcium Channel Expression and Applicability as Targeted
Therapies in Melanoma".
AB - [This corrects the article DOI: 10.1155/2015/587135.].
PMID- 27610371
TI - Corrigendum to "Type 2C Phosphatase 1 of Artemisia annua L. Is a Negative
Regulator of ABA Signaling".
AB - [This corrects the article DOI: 10.1155/2014/521794.].
PMID- 27610373
TI - A Cross-Sectional Survey to Estimate the Cat Population and Ownership Profiles in
a Semirural Area of Central Italy.
AB - Understanding animal population size and its demographic features is essential to
address Public Health policies as well as to provide valuable information to pet
industries and veterinary practitioners. Nevertheless, official data on feline
population are not available worldwide. In the present study, the owned cat
population size, its demographic attributes, and the ownership profiles have been
investigated through a face-to-face questionnaire in a semirural area of Central
Italy. The human : cat ratio was equal to 6.8 (95% CI: 5.7-7.5); 29.3% of
households own at least one cat. The majority of cats were living in a rural area
(67.8%) and outdoors, were neutered (70.5%), and were fed with commercial food
(54.8%) and they visited a veterinarian 1-2 times a year (43.3%). The cat
ownership was strongly associated with people living in a rural area and owning
another pet. As the cat owned population was mainly kept outdoors in rural areas,
the possible relation between the owned and the stray animals is worthy to be
monitored in future researches. Our study revealed that the feline owned
population was larger than expected and that social and economic human factors do
not influence the cat ownership. Health Authorities and veterinary practitioners
should promote responsible ownership to increase the veterinary care, to
intensify the official identification, and to properly manage the outdoor
lifestyle.
PMID- 27610372
TI - Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative
for Cancer Treatment.
AB - In eukaryotes, genes are frequently interrupted with noncoding sequences named
introns. Alternative splicing is a nuclear mechanism by which these introns are
removed and flanking coding regions named exons are joined together to generate a
message that will be translated in the cytoplasm. This mechanism is catalyzed by
a complex machinery known as the spliceosome, which is conformed by more than 300
proteins and ribonucleoproteins that activate and regulate the precision of gene
expression when assembled. It has been proposed that several genetic diseases are
related to defects in the splicing process, including cancer. For this reason,
natural products that show the ability to regulate splicing have attracted
enormous attention due to its potential use for cancer treatment. Some microbial
metabolites have shown the ability to inhibit gene splicing and the molecular
mechanism responsible for this inhibition is being studied for future
applications. Here, we summarize the main types of natural products that have
been characterized as splicing inhibitors, the recent advances regarding
molecular and cellular effects related to these molecules, and the applications
reported so far in cancer therapeutics.
PMID- 27610374
TI - Corrigendum to "Effects of Sevoflurane and Propofol on Organ Blood Flow in Left
Ventricular Assist Devices in Pigs".
AB - [This corrects the article DOI: 10.1155/2015/898373.].
PMID- 27610375
TI - Integrated Analysis of DNA Methylation and mRNA Expression Profiles Data to
Identify Key Genes in Lung Adenocarcinoma.
AB - Introduction. Lung adenocarcinoma (LAC) is the most frequent type of lung cancer
and has a high metastatic rate at an early stage. This study is aimed at
identifying LAC-associated genes. Materials and Methods. GSE62950 downloaded from
Gene Expression Omnibus included a DNA methylation dataset and an mRNA expression
profiles dataset, both of which included 28 LAC tissue samples and 28 adjacent
normal tissue samples. The differentially expressed genes (DEGs) were screened by
Limma package in R, and their functions were predicted by enrichment analysis
using TargetMine online tool. Then, protein-protein interaction (PPI) network was
constructed using STRING and Cytoscape. Finally, LAC-associated methylation sites
were identified by CpGassoc package in R and mapped to the DEGs to obtain LAC
associated DEGs. Results. Total 913 DEGs were identified in LAC tissues. In the
PPI networks, MAD2L1, AURKB, CCNB2, CDC20, and WNT3A had higher degrees, and the
first four genes might be involved in LAC through interaction. Total 8856 LAC
associated methylation sites were identified and mapped to the DEGs. And there
were 29 LAC-associated methylation sites located in 27 DEGs (e.g., SH3GL2, BAI3,
CDH13, JAM2, MT1A, LHX6, and IGFBP3). Conclusions. These key genes might play a
role in pathogenesis of LAC.
PMID- 27610376
TI - Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and
Impairs Barrier Function in Mice.
AB - The purpose of this study was to explore relationships between low dose dietary
supplementation with chitosan (COS) and body weight, feed intake, intestinal
barrier function, and permeability in mice. Twenty mice were randomly assigned to
receive an unadulterated control diet (control group) or a dietary
supplementation with 30 mg/kg dose of chitosan (COS group) for two weeks. Whilst
no significant differences were found between the conditions for body weight or
food and water intake, mice in the COS group had an increased serum D-lactate
content (P < 0.05) and a decreased jejunal diamine oxidase (DAO) activity (P <
0.05). Furthermore, mice in COS group displayed a reduced expression of occludin
and ZO-1 (P < 0.05) and a reduced expression of occludin in the ileum (P < 0.05).
The conclusion drawn from these findings showed that although 30 mg/kg COS
supplemented diet had no effect on body weight or feed intake in mice, this
dosage may compromise intestinal barrier function and permeability. This research
will contribute to the guidance on COS supplements.
PMID- 27610377
TI - Differential Intracochlear Sound Pressure Measurements in Human Temporal Bones
with an Off-the-Shelf Sensor.
AB - The standard method to determine the output level of acoustic and mechanical
stimulation to the inner ear is measurement of vibration response of the stapes
in human cadaveric temporal bones (TBs) by laser Doppler vibrometry. However,
this method is reliable only if the intact ossicular chain is stimulated. For
other stimulation modes an alternative method is needed. The differential
intracochlear sound pressure between scala vestibuli (SV) and scala tympani (ST)
is assumed to correlate with excitation. Using a custom-made pressure sensor it
has been successfully measured and used to determine the output level of acoustic
and mechanical stimulation. To make this method generally accessible, an off-the
shelf pressure sensor (Samba Preclin 420 LP, Samba Sensors) was tested here for
intracochlear sound pressure measurements. During acoustic stimulation,
intracochlear sound pressures were simultaneously measurable in SV and ST between
0.1 and 8 kHz with sufficient signal-to-noise ratios with this sensor. The
pressure differences were comparable to results obtained with custom-made
sensors. Our results demonstrated that the pressure sensor Samba Preclin 420 LP
is usable for measurements of intracochlear sound pressures in SV and ST and for
the determination of differential intracochlear sound pressures.
PMID- 27610378
TI - Tomographic Ultrasound Imaging to Control the Placement of Tension-Free
Transobturator Tape in Female Urinary Stress Incontinence.
AB - Purpose. The objective was to evaluate, by means of tomographic ultrasound
imaging (TUI), the reliability of a novel approach for determining the position
of the implanted tension-free transobturator tape (TOT). Furthermore, we analyzed
the association between the position of the tape at rest and the subjective cure
in stress incontinent women. Methods. This retrospective pilot study consists of
32 stress incontinent women, who underwent TOT procedure and routine sonographic
control at day 1 postoperatively and at follow-up visit. TUI was applied on the
resulting 4D volumes, thereby delivering 9 axial slices with a 4 mm interslice
distance starting at the meatus urethrae internus in caudal direction. The
reliability of the approach was tested by two examiners. Postoperative and follow
up ultrasound parameters of uncured and cured patients were analyzed. Results.
Measurements of the position of the TOT demonstrated high intraclass correlation
coefficients. We found minor differences between sonographic parameters at day 1
postoperatively and at follow-up after a median period of 321 days. In cured
patients, the position of the tape was measured in a more caudal position than in
uncured patients. Conclusions. TUI can be a reliable method for determining the
position of the tape. Further studies are needed to evaluate whether the
postoperatively determined position can be used as an indicator of future
subjective cure.
PMID- 27610379
TI - Age-Associated Changes in the Spectral and Statistical Parameters of Surface
Electromyogram of Tibialis Anterior.
AB - Age-related neuromuscular change of Tibialis Anterior (TA) is a leading cause of
muscle strength decline among the elderly. This study has established the
baseline for age-associated changes in sEMG of TA at different levels of
voluntary contraction. We have investigated the use of Gaussianity and maximal
power of the power spectral density (PSD) as suitable features to identify age
associated changes in the surface electromyogram (sEMG). Eighteen younger (20-30
years) and 18 older (60-85 years) cohorts completed two trials of isometric
dorsiflexion at four different force levels between 10% and 50% of the maximal
voluntary contraction. Gaussianity and maximal power of the PSD of sEMG were
determined. Results show a significant increase in sEMG's maximal power of the
PSD and Gaussianity with increase in force for both cohorts. It was also observed
that older cohorts had higher maximal power of the PSD and lower Gaussianity.
These age-related differences observed in the PSD and Gaussianity could be due to
motor unit remodelling. This can be useful for noninvasive tracking of age
associated neuromuscular changes.
PMID- 27610381
TI - Experimental Model of Proximal Junctional Fracture after Multilevel Posterior
Spinal Instrumentation.
AB - There is a high risk of proximal junctional fractures (PJF) with multilevel
spinal instrumentation, especially in the osteoporotic spine. This problem is
associated with significant morbidity and possibly the need for reoperation.
Various techniques have been proposed in an attempt to decrease the risk of PJF
but there is no experimental model described for in vitro production of PJF after
multilevel instrumentation. The objective of this study is to develop an
experimental model of PJF after multilevel posterior instrumentation. Initially,
four porcine specimens including 4 vertebrae and instrumented at the 3 caudal
vertebrae using a pedicle screw construct were subjected to different loading
conditions. Loading conditions on porcine specimens involving cyclic loading
along the axis of the center vertebral body line, with constrained flexion
between 0 degrees and 15 degrees proximally, and fully constraining the
specimen distally resulted in a fracture pattern most representative of a PJF
seen clinically in humans, so to undergo human cadaveric testing with similar
loading conditions was decided. Clinically relevant PJF were produced in all 3
human specimens. The experimental model described in this study will allow the
evaluation of different parameters influencing the incidence and prevention of
PJF after multilevel posterior spinal instrumentation.
PMID- 27610380
TI - Microtubule Polymerization Functions in Hypersensitive Response and Accumulation
of H2O2 in Wheat Induced by the Stripe Rust.
AB - The plant cytoskeleton, including microtubules and microfilaments, is one of the
important factors in determining the polarity of cell division and growth, as
well as the interaction of plants with invading pathogens. In defense responses
of wheat against the stripe rust (Puccinia striiformis f. sp. tritici) infection,
hypersensitive response is the most crucial event to prevent the spread of
pathogens. In order to reveal the effect of microtubules on the hypersensitive
cell death and H2O2 accumulation in the interaction of wheat (Triticum aestivum)
cv. Suwon 11 with an incompatible race, CYR23, wheat leaves were treated with
microtubule inhibitor, oryzalin, before inoculation. The results showed that the
frequency of infection sites with hypersensitive response occurrence was
significantly reduced, and hypersensitive cell death in wheat leaves was
suppressed compared to the control. In addition, the frequency and the incidence
of infected cells with H2O2 accumulation were also reduced after the treatment
with oryzalin. Those results indicated that microtubules are related to
hypersensitive response and H2O2 accumulation in wheat induced by the stripe
rust, and depolymerization of microtubules reduces the resistance of plants to
pathogen infection in incompatible interaction, suggesting that microtubules play
a potential role in the expression of resistance of wheat against the stripe rust
fungus.
PMID- 27610382
TI - Device-Training for Individuals with Thoracic and Lumbar Spinal Cord Injury Using
a Powered Exoskeleton for Technically Assisted Mobility: Achievements and User
Satisfaction.
AB - Objective. Results of a device-training for nonambulatory individuals with
thoracic and lumbar spinal cord injury (SCI) using a powered exoskeleton for
technically assisted mobility with regard to the achieved level of control of the
system after training, user satisfaction, and effects on quality of life (QoL).
Methods. Observational single centre study with a 4-week to 5-week intensive
inpatient device-training using a powered exoskeleton (ReWalkTM). Results. All 7
individuals with SCI who commenced the device-training completed the course of
training and achieved basic competences to use the system, that is, the ability
to stand up, sit down, keep balance while standing, and walk indoors, at least
with a close contact guard. User satisfaction with the system and device-training
was documented for several aspects. The quality of life evaluation (SF-12v2TM)
indicated that the use of the powered exoskeleton can have positive effects on
the perception of individuals with SCI regarding what they can achieve
physically. Few adverse events were observed: minor skin lesions and irritations
were observed; no falls occurred. Conclusions. The device-training for
individuals with thoracic and lumbar SCI was effective and safe. All trained
individuals achieved technically assisted mobility with the exoskeleton while
still needing a close contact guard.
PMID- 27610383
TI - A Cross-Sectional Population-Based Survey of Trachoma among Migrant School Aged
Children in Shanghai, China.
AB - We investigated the prevalence of clinical trachoma in 154,265 children aged 6 to
16 years in 206 Shanghai migrant schools. Clean water availability in school,
each child's facial cleanliness, eyelids, corneas, and the presenting distance
visual acuities were examined. Trachoma was clinically diagnosed in accordance
with the World Health Organization simplified classification. Eyes diagnosed with
trachoma were swabbed to test for ocular Chlamydia trachomatis infections (OCTI)
with a rapid latex immunochromatographic test. Among 153,977 students, no
blindness was found related to trachoma. Trachoma was diagnosed in 8029 children
(5.2%). In 87 schools clinical trachoma prevalence was higher than 5%. OCTI was
confirmed in 2073 of 6823 trachoma diagnosed children (30.4%). Clinical trachoma
prevalence was higher among females than males (p < 0.001), but gender comparison
showed no statistical difference in the prevalence of OCTI (p = 0.077). Age and
clinical trachoma (r = -0.014; p < 0.001) or OCTI (r = -0.026; p = 0.031)
prevalence were negatively correlated. Clinical trachoma was different in
different districts and counties (p < 0.001). Trachoma warrants close attention
in Shanghai migrant children because the condition remains endemic in some
schools.
PMID- 27610384
TI - Gamma-Ray Treatment of Echinococcus Protoscoleces prior to Implantation in Mice
Reduces Echinococcosis.
AB - Echinococcosis is a serious parasitic disease caused by Echinococcus tapeworms.
Protoscoleces are sometimes released during surgical treatment for hydatid cysts,
causing the recurrence of echinococcosis. Protoscoleces may be susceptible to
radiation therapy. In this study Echinococcus protoscoleces were cultured in
vitro and then divided into four different gamma-ray irradiation dose groups (10
Gy, 20 Gy, 40 Gy, and 80 Gy) and a blank group. The protoscoleces were then
implanted into the abdominal cavity of mice. Four months later, we observed that
the incidence and weight of cysts declined with the increase of irradiation dose.
gamma-ray irradiation can suppress the generation of Echinococcus originated from
protoscolex, the reason of which is due to the damaging to the structure of
Echinococcus. Irradiation may prevent echinococcosis recurrence after surgical
removal of hydatid cysts.
PMID- 27610385
TI - Anaplasma marginale: Diversity, Virulence, and Vaccine Landscape through a
Genomics Approach.
AB - In order to understand the genetic diversity of A. marginale, several efforts
have been made around the world. This rickettsia affects a significant number of
ruminants, causing bovine anaplasmosis, so the interest in its virulence and how
it is transmitted have drawn interest not only from a molecular point of view but
also, recently, some genomics research have been performed to elucidate genes and
proteins with potential as antigens. Unfortunately, so far, we still do not have
a recombinant anaplasmosis vaccine. In this review, we present a landscape of the
multiple approaches carried out from the genomic perspective to generate valuable
information that could be used in a holistic way to finally develop an
anaplasmosis vaccine. These approaches include the analysis of the genetic
diversity of A. marginale and how this affects control measures for the disease.
Anaplasmosis vaccine development is also reviewed from the conventional
vaccinomics to genome-base vaccinology approach based on proteomics,
metabolomics, and transcriptomics analyses reported. The use of these new omics
approaches will undoubtedly reveal new targets of interest in the near future,
comprising information of potential antigens and the immunogenic effect of A.
marginale proteins.
PMID- 27610386
TI - PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies.
AB - Platelet-Rich Plasma (PRP) has been widely used in orthopaedic surgery and sport
medicine to treat tendon injuries. However, the efficacy of PRP treatment for
tendinopathy is controversial. This paper focuses on reviewing the basic science
studies on PRP performed under well-controlled conditions. Both in vitro and in
vivo studies describe PRP's anabolic and anti-inflammatory effects on tendons.
While some clinical trials support these findings, others refute them. In this
review, we discuss the effectiveness of PRP to treat tendon injuries with
evidence presented in basic science studies and the potential reasons for the
controversial results in clinical trials. Finally, we comment on the approaches
that may be required to improve the efficacy of PRP treatment for tendinopathy.
PMID- 27610387
TI - SABinder: A Web Service for Predicting Streptavidin-Binding Peptides.
AB - Streptavidin is sometimes used as the intended target to screen phage-displayed
combinatorial peptide libraries for streptavidin-binding peptides (SBPs). More
often in the biopanning system, however, streptavidin is just a commonly used
anchoring molecule that can efficiently capture the biotinylated target. In this
case, SBPs creeping into the biopanning results are not desired binders but
target-unrelated peptides (TUP). Taking them as intended binders may mislead
subsequent studies. Therefore, it is important to find if a peptide is likely to
be an SBP when streptavidin is either the intended target or just the anchoring
molecule. In this paper, we describe an SVM-based ensemble predictor called
SABinder. It is the first predictor for SBP. The model was built with the feature
of optimized dipeptide composition. It was observed that 89.20% (MCC = 0.78; AUC
= 0.93; permutation test, p < 0.001) of peptides were correctly classified. As a
web server, SABinder is freely accessible. The tool provides a highly efficient
way to exclude potential SBP when they are TUP or to facilitate identification of
possibly new SBP when they are the desired binders. In either case, it will be
helpful and can benefit related scientific community.
PMID- 27610388
TI - Roles of Peroxisomes in the Rice Blast Fungus.
AB - The rice blast fungus, Magnaporthe oryzae, is a model plant pathogenic fungus and
is a severe threat to global rice production. Over the past two decades, it has
been found that the peroxisomes play indispensable roles during M. oryzae
infection. Given the importance of the peroxisomes for virulence, we review
recent advances of the peroxisomes roles during M. oryzae infection processes. We
firstly introduce the molecular mechanisms and life cycles of the peroxisomes.
And then, metabolic functions related to the peroxisomes are also discussed.
Finally, we provide an overview of the relationship between peroxisomes and
pathogenicity.
PMID- 27610389
TI - QuaBingo: A Prediction System for Protein Quaternary Structure Attributes Using
Block Composition.
AB - Background. Quaternary structures of proteins are closely relevant to gene
regulation, signal transduction, and many other biological functions of proteins.
In the current study, a new method based on protein-conserved motif composition
in block format for feature extraction is proposed, which is termed block
composition. Results. The protein quaternary assembly states prediction system
which combines blocks with functional domain composition, called QuaBingo, is
constructed by three layers of classifiers that can categorize quaternary
structural attributes of monomer, homooligomer, and heterooligomer. The building
of the first layer classifier uses support vector machines (SVM) based on blocks
and functional domains of proteins, and the second layer SVM was utilized to
process the outputs of the first layer. Finally, the result is determined by the
Random Forest of the third layer. We compared the effectiveness of the
combination of block composition, functional domain composition, and pseudoamino
acid composition of the model. In the 11 kinds of functional protein families,
QuaBingo is 23% of Matthews Correlation Coefficient (MCC) higher than the
existing prediction system. The results also revealed the biological
characterization of the top five block compositions. Conclusions. QuaBingo
provides better predictive ability for predicting the quaternary structural
attributes of proteins.
PMID- 27610391
TI - Pilot Study of a Web-Delivered Multicomponent Intervention for Rural Teens with
Poorly Controlled Type 1 Diabetes.
AB - Objective. The purpose of this study was to examine the feasibility and
effectiveness of a web-delivered multicomponent behavioral and family-based
intervention targeting self-regulation and self-monitoring of blood glucose
levels (SMBG) and glycemic control (HbA1c) in teens with type 1 diabetes (T1DM)
living in rural US. Methods. 15 teens with poorly controlled T1DM participated in
a 25-week web-delivered intervention with two phases, active treatment (weekly
treatment sessions and working memory training program) and maintenance treatment
(fading of treatment sessions). Results. Almost all (13 of 15) participants
completed at least 14 of 15 treatment sessions and at least 20 of 25 working
memory training sessions. SMBG was increased significantly at end of active and
maintenance treatment, and HbA1c was decreased at end of active treatment (p's <=
0.05). Executive functioning improved at end of maintenance treatment:
performance on working memory and inhibitory control tasks significantly improved
(p's <= 0.02) and parents reported fewer problems with executive functioning (p =
0.05). Improvement in inhibitory control was correlated with increases in SMBG
and decreases in HbA1c. Conclusions. An innovative web-delivered and
multicomponent intervention was feasible for teens with poorly controlled T1DM
and their families living in rural US and associated with significant
improvements in SMBG and HbA1c.
PMID- 27610390
TI - Metainflammation in Diabetic Coronary Artery Disease: Emerging Role of Innate and
Adaptive Immune Responses.
AB - Globally, noncommunicable chronic diseases such as Type-2 Diabetes Mellitus
(T2DM) and Coronary Artery Disease (CAD) are posing a major threat to the world.
T2DM is known to potentiate CAD which had led to the coining of a new clinical
entity named diabetic CAD (DM-CAD), leading to excessive morbidity and mortality.
The synergistic interaction between these two comorbidities is through sterile
inflammation which is now being addressed as metabolic inflammation or
metainflammation, which plays a pivotal role during both early and late stages of
T2DM and also serves as a link between T2DM and CAD. This review summarises the
current concepts on the role played by both innate and adaptive immune responses
in setting up metainflammation in DM-CAD. More specifically, the role played by
innate pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), NOD1
like receptors (NLRs), Rig-1-like receptors (RLRs), and C-type lectin like
receptors (CLRs) and metabolic endotoxemia in fuelling metainflammation in DM-CAD
would be discussed. Further, the role played by adaptive immune cells (Th1, Th2,
Th17, and Th9 cells) in fuelling metainflammation in DM-CAD will also be
discussed.
PMID- 27610393
TI - Soluble HLA-G and HLA-E Levels in Bone Marrow Plasma Samples Are Related to
Disease Stage in Neuroblastoma Patients.
AB - The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the
progression of Neuroblastoma (NB), the most common pediatric extracranial solid
tumor, has been characterized in the last years. Since BM infiltration by NB
cells is an adverse prognostic factor, we have here analyzed for the first time
the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma
samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are
present in BM plasma samples, and their levels were similar between NB patients
and controls, thus suggesting that these molecules are physiologically released
by resident or stromal BM cell populations. This hypothesis was supported by the
finding that sHLA-G and sHLA-E levels did not correlate with BM infiltration and
other adverse prognostic factors (MYCN amplification and age at diagnosis). In
contrast, BM plasma levels of both molecules were higher in patients with
metastatic disease than in patients with localized NB, thus suggesting that
concentration of these molecules might be correlated with disease progression.
The prognostic role of sHLA-G and sHLA-E concentration in the BM plasma for NB
patients will be evaluated in future studies, by analyzing the clinical outcome
of the same NB patients at follow-up.
PMID- 27610392
TI - Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High
Grade Neuroblastoma.
AB - We designed multimodal tumor vaccine that consists of irradiated tumor cells
infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was
tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the
right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via
intramuscular injection of multimodal vaccine or uninfected irradiated tumor
cells at seven and 14 days after tumor establishment. While there was no survival
difference between groups vaccinated with cell-based vaccine applied following
tumor injection, a premunition prime/boost vaccination strategy produced a
significant survival advantage in both groups and sustained immune response to an
intracranial rechallenge of the same tumor. The syngeneic but unrelated H6
hepatocellular tumor cell line grew unrestricted in vaccinated mice, indicative
of vaccine-mediated specific immunity to Neuro 2a tumors. Longitudinal analyses
of tumor-infiltrating lymphocytes revealed a primary adaptive T cell response
involving both CD4+ and CD8+ T cell subsets. Spleen cell mononuclear preparations
from vaccinated mice were significantly more cytotoxic to Neuro 2a tumor cells
than spleen cells from control mice as demonstrated in a four-hour in vitro
cytotoxicity assay. These results strongly suggest that an irradiated whole cell
tumor vaccine incorporating IL-12-expressing M002 HSV can produce a durable,
specific immunization in a murine model of intracranial tumor.
PMID- 27610394
TI - Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat
critical limb ischemia.
AB - Numerous clinical trials are utilizing mesenchymal stem cells (MSC) to treat
critical limb ischemia, primarily for their ability to secrete signals that
promote revascularization. These cells have demonstrated clinical safety, but
their efficacy has been limited, possibly because these paracrine signals are
secreted at subtherapeutic levels. In these studies the combination of cell and
gene therapy was evaluated by engineering MSC with a lentivirus to overexpress
vascular endothelial growth factor (VEGF). To achieve clinical compliance, the
number of viral insertions was limited to 1-2 copies/cell and a constitutive
promoter with demonstrated clinical safety was used. MSC/VEGF showed
statistically significant increases in blood flow restoration as compared with
sham controls, and more consistent improvements as compared with nontransduced
MSC. Safety of MSC/VEGF was assessed in terms of genomic stability, rule-out
tumorigenicity, and absence of edema or hemangiomas in vivo. In terms of
retention, injected MSC/VEGF showed a steady decline over time, with a very small
fraction of MSC/VEGF remaining for up to 4.5 months. Additional safety studies
completed include absence of replication competent lentivirus, sterility tests,
and absence of VSV-G viral envelope coding plasmid. These preclinical studies are
directed toward a planned phase 1 clinical trial to treat critical limb ischemia.
PMID- 27610395
TI - Design for a coherent-scatter imaging system compatible with screening
mammography.
AB - A system using a wide-slot beam and simple antiscatter grids or slots has been
designed to provide a localized map of tissue type that could be overlaid on the
simultaneous conventional transmission image to provide an inexpensive, low dose
adjunct to conventional screening mammography. Depth information is obtainable
from the stereoscopic viewing angles. The system was demonstrated to produce
observable contrast between adipose tissue and a phantom chosen to mimic
carcinoma at an exposure comparable with screening mammography. Imaging data was
collected over a range of system parameters to optimize contrast and to allow
verification of simulation modeling.
PMID- 27610397
TI - Coherent scatter imaging Monte Carlo simulation.
AB - Conventional mammography can suffer from poor contrast between healthy and
cancerous tissues due to the small difference in attenuation properties. Coherent
scatter slot scan imaging is an imaging technique which provides additional
information and is compatible with conventional mammography. A Monte Carlo
simulation of coherent scatter slot scan imaging was performed to assess its
performance and provide system optimization. Coherent scatter could be exploited
using a system similar to conventional slot scan mammography system with
antiscatter grids tilted at the characteristic angle of cancerous tissues. System
optimization was performed across several parameters, including source voltage,
tilt angle, grid distances, grid ratio, and shielding geometry. The simulated
carcinomas were detectable for tumors as small as 5 mm in diameter, so coherent
scatter analysis using a wide-slot setup could be promising as an enhancement for
screening mammography. Employing coherent scatter information simultaneously with
conventional mammography could yield a conventional high spatial resolution image
with additional coherent scatter information.
PMID- 27610396
TI - Development and validation of a segmentation-free polyenergetic algorithm for
dynamic perfusion computed tomography.
AB - Dynamic perfusion imaging can provide the morphologic details of the scanned
organs as well as the dynamic information of blood perfusion. However, due to the
polyenergetic property of the x-ray spectra, beam hardening effect results in
undesirable artifacts and inaccurate CT values. To address this problem, this
study proposes a segmentation-free polyenergetic dynamic perfusion imaging
algorithm (pDP) to provide superior perfusion imaging. Dynamic perfusion usually
is composed of two phases, i.e., a precontrast phase and a postcontrast phase. In
the precontrast phase, the attenuation properties of diverse base materials
(e.g., in a thorax perfusion exam, base materials can include lung, fat, breast,
soft tissue, bone, and metal implants) can be incorporated to reconstruct
artifact-free precontrast images. If patient motions are negligible or can be
corrected by registration, the precontrast images can then be employed as a
priori information to derive linearized iodine projections from the postcontrast
images. With the linearized iodine projections, iodine perfusion maps can be
reconstructed directly without the influence of various influential factors, such
as iodine location, patient size, x-ray spectrum, and background tissue type. A
series of simulations were conducted on a dynamic iodine calibration phantom and
a dynamic anthropomorphic thorax phantom to validate the proposed algorithm. The
simulations with the dynamic iodine calibration phantom showed that the proposed
algorithm could effectively eliminate the beam hardening effect and enable
quantitative iodine map reconstruction across various influential factors. The
error range of the iodine concentration factors ([Formula: see text]) was reduced
from [Formula: see text] for filtered back-projection (FBP) to [Formula: see
text] for pDP. The quantitative results of the simulations with the dynamic
anthropomorphic thorax phantom indicated that the maximum error of iodine
concentrations can be reduced from [Formula: see text] for FBP to less than
[Formula: see text] for pDP, which suggested that the proposed algorithm could
not only effectively eliminate beam hardening artifacts but also significantly
reduce the influence of the metal artifacts and accurately reconstruct the iodine
map regardless of the influential factors. A segmentation-free polyenergetic
dynamic perfusion imaging algorithm was proposed and validated via simulations.
This method can accurately reconstruct artifact-free iodine maps for quantitative
analyses.
PMID- 27610398
TI - Quantification of sun-related changes in the eye in conjunctival ultraviolet
autofluorescence images.
AB - Quantification of sun-related changes in conjunctival ultraviolet
autofluorescence (CUVAF) images is a subjective and tedious task, in which
reproducibility of results is difficult. Thus, we have developed a semiautomatic
method in MATLAB((r)) to analyze CUVAF images retrospectively. The algorithm was
validated on 200 images from 50 randomly selected participants from the Western
Australian Pregnancy Cohort (Raine) study 20-year follow-up assessment, in which
CUVAF area measurements were available from previous manual analysis. Algorithm
performance was compared to manual measurements and yielded better than 95%
correspondence in both intra- and interobserver agreement. Furthermore, the
semiautomatic method significantly reduced analysis time by 50%.
PMID- 27610399
TI - Digital mammographic tumor classification using transfer learning from deep
convolutional neural networks.
AB - Convolutional neural networks (CNNs) show potential for computer-aided diagnosis
(CADx) by learning features directly from the image data instead of using
analytically extracted features. However, CNNs are difficult to train from
scratch for medical images due to small sample sizes and variations in tumor
presentations. Instead, transfer learning can be used to extract tumor
information from medical images via CNNs originally pretrained for nonmedical
tasks, alleviating the need for large datasets. Our database includes 219 breast
lesions (607 full-field digital mammographic images). We compared support vector
machine classifiers based on the CNN-extracted image features and our prior
computer-extracted tumor features in the task of distinguishing between benign
and malignant breast lesions. Five-fold cross validation (by lesion) was
conducted with the area under the receiver operating characteristic (ROC) curve
as the performance metric. Results show that classifiers based on CNN-extracted
features (with transfer learning) perform comparably to those using analytically
extracted features [area under the ROC curve [Formula: see text]]. Further, the
performance of ensemble classifiers based on both types was significantly better
than that of either classifier type alone ([Formula: see text] versus 0.81,
[Formula: see text]). We conclude that transfer learning can improve current CADx
methods while also providing standalone classifiers without large datasets,
facilitating machine-learning methods in radiomics and precision medicine.
PMID- 27610400
TI - Abdomen and spinal cord segmentation with augmented active shape models.
AB - Active shape models (ASMs) have been widely used for extracting human anatomies
in medical images given their capability for shape regularization of topology
preservation. However, sensitivity to model initialization and local
correspondence search often undermines their performances, especially around
highly variable contexts in computed-tomography (CT) and magnetic resonance (MR)
images. In this study, we propose an augmented ASM (AASM) by integrating the
multiatlas label fusion (MALF) and level set (LS) techniques into the traditional
ASM framework. Using AASM, landmark updates are optimized globally via a region
based LS evolution applied on the probability map generated from MALF. This
augmentation effectively extends the searching range of correspondent landmarks
while reducing sensitivity to the image contexts and improves the segmentation
robustness. We propose the AASM framework as a two-dimensional segmentation
technique targeting structures with one axis of regularity. We apply AASM
approach to abdomen CT and spinal cord (SC) MR segmentation challenges. On 20 CT
scans, the AASM segmentation of the whole abdominal wall enables the
subcutaneous/visceral fat measurement, with high correlation to the measurement
derived from manual segmentation. On 28 3T MR scans, AASM yields better
performances than other state-of-the-art approaches in segmenting white/gray
matter in SC.
PMID- 27610401
TI - Membrane Transporters and Pharmacological Implications.
PMID- 27610405
TI - Back to the Lecture.
PMID- 27610403
TI - Hepatitis C Virus in North Africa: An Emerging Threat.
AB - Hepatitis C virus is a major public health threat associated with serious
clinical consequences worldwide. North Africa is a unique region composed of
seven countries that vary considerably in the predisposing factors to microbial
diseases both historically and at the present time. The dynamics of HCV in the
region are not well documented. The data are both limited and controversial in
most of the countries in the region. In North Africa, the epidemiology of HCV is
disparate and understanding it has been hampered by regional "epidemiological
homogeneity" concepts. As the dynamics of HCV vary from country to country,
context-specific research is needed. In this review, we assess studies performed
in each country in the general populations as well as among blood donors and
groups exposed to the HCV infection. The reported prevalence of HCV ranges from
0.6% to 8.4% in the Maghreb countries and is predominated by genotype 1. In the
Nile valley region, it ranges from 2.2% to 18.9% and is dominated by genotype 4.
In North African countries, HCV seems to be a serious problem that is driven by
different vectors even in different geographical locations within the same
country. Efforts should be combined at both the national and regional levels to
implement efficient preventive and treatment strategies.
PMID- 27610406
TI - A Conversation with Helen Sharman.
PMID- 27610402
TI - Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation
transcription coupling.
AB - During the last two decades numerous research teams demonstrated that skeletal
muscles function as an exercise-dependent endocrine organ secreting dozens of
myokines. Variety of physiological and pathophysiological implications of
skeletal muscle myokines secretion has been described; however, upstream signals
and sensing mechanisms underlying this phenomenon remain poorly understood. It is
well documented that in skeletal muscles intensive exercise triggers dissipation
of transmembrane gradient of monovalent cations caused by permanent activation of
voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained
elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous
genes including several canonical myokines, such as interleukin 6 and
cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators.
These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i
independent mechanism of excitation-transcription coupling which triggers myokine
production. This pathway exists in parallel with canonical signaling mediated by
Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1alpha (HIF
1alpha). In our mini-review we briefly summarize data supporting this hypothesis
as well as unresolved issues aiming to forthcoming studies.
PMID- 27610407
TI - The Record Breakers.
PMID- 27610404
TI - Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility
and Early Disease Activity in Rheumatoid Arthritis.
AB - Purpose/Background. Mounting evidence designates that HLA-G plays a role in the
regulation of inflammatory processes and autoimmune diseases. There are
controversial reports concerning the impact of HLA-G gene polymorphism on
rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp
ins/del and +3142G>C polymorphism with susceptibility and early disease activity
in RA patients in a sample of the Iranian population. Methods. This case-control
study was done on 194 patients with RA and 158 healthy subjects. The HLA-G
rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by
polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and
PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly
decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38-0.97, p = 0.038,
GC versus GG; OR = 0.36, 95% CI = 0.14-0.92, p = 0.034, CC versus GG), dominant
(OR = 0.56, 95% CI = 0.36-0.87, p = 0.011, GC + CC versus GG), and allele (OR =
0.58, 95% CI = 0.41-0.84, p = 0.004, C versus G) inheritance models tested. Our
finding did not support an association between HLA-G 14 bp ins/del variant and
risk/protection of RA. In addition, no significant association was found between
the polymorphism and early disease activity. Conclusion. In summary, our results
showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of
RA in a sample of the Iranian population.
PMID- 27610408
TI - Tetrazine Marks the Spot.
PMID- 27610409
TI - Reducing Them Down To Charge Them Up: Low Temperature Catalyst Activation.
PMID- 27610410
TI - Radiochemistry, PET Imaging, and the Internet of Chemical Things.
AB - The Internet of Chemical Things (IoCT), a growing network of computers, mobile
devices, online resources, software suites, laboratory equipment, synthesis
apparatus, analytical devices, and a host of other machines, all interconnected
to users, manufacturers, and others through the infrastructure of the Internet,
is changing how we do chemistry. While in its infancy across many chemistry
laboratories and departments, it became apparent when considering our own work
synthesizing radiopharmaceuticals for positron emission tomography (PET) that a
more mature incarnation of the IoCT already exists. How does the IoCT impact our
lives today, and what does it hold for the smart (radio)chemical laboratories of
the future?
PMID- 27610411
TI - Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25
and FRB in Live Cells.
AB - Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular
metabolism, and control of the mTOR pathway by rapamycin shows potential for the
treatment of metabolic diseases. In this study, we employed a new proximity
biotin-labeling method using promiscuous biotin ligase (pBirA) to identify
unknown elements in the rapamycin-induced interactome on the FK506-rapamycin
binding (FRB) domain in living cells. FKBP25 showed the strongest biotin labeling
by FRB-pBirA in the presence of rapamycin. Immunoprecipitation and
immunofluorescence experiments confirmed that endogenous FKBP25 has a rapamycin
induced physical interaction with the FRB domain. Furthermore, the crystal
structure of the ternary complex of FRB-rapamycin-FKBP25 was determined at 1.67-A
resolution. In this crystal structure we found that the conformational changes of
FRB generate a hole where there is a methionine-rich space, and covalent
metalloid coordination was observed at C2085 of FRB located at the bottom of the
hole. Our results imply that FKBP25 might have a unique physiological role
related to metallomics in mTOR signaling.
PMID- 27610412
TI - Observation of van Hove Singularities in Twisted Silicene Multilayers.
AB - Interlayer interactions perturb the electronic structure of two-dimensional
materials and lead to new physical phenomena, such as van Hove singularities and
Hofstadter's butterfly pattern. Silicene, the recently discovered two-dimensional
form of silicon, is quite unique, in that silicon atoms adopt competing sp(2) and
sp(3) hybridization states leading to a low-buckled structure promising
relatively strong interlayer interaction. In multilayer silicene, the stacking
order provides an important yet rarely explored degree of freedom for tuning its
electronic structures through manipulating interlayer coupling. Here, we report
the emergence of van Hove singularities in the multilayer silicene created by an
interlayer rotation. We demonstrate that even a large-angle rotation (>20 degrees
) between stacked silicene layers can generate a Moire pattern and van Hove
singularities due to the strong interlayer coupling in multilayer silicene. Our
study suggests an intriguing method for expanding the tunability of the
electronic structure for electronic applications in this two-dimensional
material.
PMID- 27610413
TI - Tracking a Common Surface-Bound Intermediate during CO2-to-Fuels Catalysis.
AB - Rational design of selective CO2-to-fuels electrocatalysts requires direct
knowledge of the electrode surface structure during turnover. Metallic Cu is the
most versatile CO2-to-fuels catalyst, capable of generating a wide array of value
added products, including methane, ethylene, and ethanol. All of these products
are postulated to form via a common surface-bound CO intermediate. Therefore, the
kinetics and thermodynamics of CO adsorption to Cu play a central role in
determining fuel-formation selectivity and efficiency, highlighting the need for
direct observation of CO surface binding equilibria under catalytic conditions.
Here, we synthesize nanostructured Cu films adhered to IR-transparent Si prisms,
and we find that these Cu surfaces enhance IR absorption of bound molecules.
Using these films as electrodes, we examine Cu-catalyzed CO2 reduction in situ
via IR spectroelectrochemistry. We observe that Cu surfaces bind electrogenerated
CO, derived from CO2, beginning at -0.60 V vs RHE with increasing surface
population at more negative potentials. Adsorbed CO is in dynamic equilibrium
with dissolved (13)CO and exchanges rapidly under catalytic conditions. The CO
adsorption profiles are pH independent, but adsorbed CO species undergo a
reversible transformation on the surface in modestly alkaline electrolytes. These
studies establish the potential, concentration, and pH dependencies of the CO
surface population on Cu, which serve to maintain a pool of this vital
intermediate primed for further reduction to higher order fuel products.
PMID- 27610414
TI - Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network.
AB - Most small-molecule drug candidates fail before entering the market, frequently
because of unexpected toxicity. Often, toxicity is detected only late in drug
development, because many types of toxicities, especially idiosyncratic adverse
drug reactions (IADRs), are particularly hard to predict and detect. Moreover,
drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn
from the market and causes 50% of acute liver failure cases in the United States.
A common mechanism often underlies many types of drug toxicities, including both
DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive
metabolites, which then conjugate to sites in proteins or DNA to form adducts.
DNA adducts are often mutagenic and may alter the reading and copying of genes
and their regulatory elements, causing gene dysregulation and even triggering
cancer. Similarly, protein adducts can disrupt their normal biological functions
and induce harmful immune responses. Unfortunately, reactive metabolites are not
reliably detected by experiments, and it is also expensive to test drug
candidates for potential to form DNA or protein adducts during the early stages
of drug development. In contrast, computational methods have the potential to
quickly screen for covalent binding potential, thereby flagging problematic
molecules and reducing the total number of necessary experiments. Here, we train
a deep convolution neural network-the XenoSite reactivity model-using literature
data to accurately predict both sites and probability of reactivity for molecules
with glutathione, cyanide, protein, and DNA. On the site level, cross-validated
predictions had area under the curve (AUC) performances of 89.8% for DNA and
94.4% for protein. Furthermore, the model separated molecules electrophilically
reactive with DNA and protein from nonreactive molecules with cross-validated AUC
performances of 78.7% and 79.8%, respectively. On both the site- and molecule
level, the model's performances significantly outperformed reactivity indices
derived from quantum simulations that are reported in the literature. Moreover,
we developed and applied a selectivity score to assess preferential reactions
with the macromolecules as opposed to the common screening traps. For the entire
data set of 2803 molecules, this approach yielded totals of 257 (9.2%) and 227
(8.1%) molecules predicted to be reactive only with DNA and protein,
respectively, and hence those that would be missed by standard reactivity
screening experiments. Site of reactivity data is an underutilized resource that
can be used to not only predict if molecules are reactive, but also show where
they might be modified to reduce toxicity while retaining efficacy. The XenoSite
reactivity model is available at http://swami.wustl.edu/xenosite/p/reactivity.
PMID- 27610415
TI - Electrochemical Partial Reforming of Ethanol into Ethyl Acetate Using Ultrathin
Co3O4 Nanosheets as a Highly Selective Anode Catalyst.
AB - Electrochemical partial reforming of organics provides an alternative strategy to
produce valuable organic compounds while generating H2 under mild conditions. In
this work, highly selective electrochemical reforming of ethanol into ethyl
acetate is successfully achieved by using ultrathin Co3O4 nanosheets with exposed
(111) facets as an anode catalyst. Those nanosheets were synthesized by a one
pot, templateless hydrothermal method with the use of ammonia. NH3 was
demonstrated critical to the overall formation of ultrathin Co3O4 nanosheets.
With abundant active sites on Co3O4 (111), the as-synthesized ultrathin Co3O4
nanosheets exhibited enhanced electrocatalytic activities toward water and
ethanol oxidations in alkaline media. More importantly, over the Co3O4
nanosheets, the electrooxidation from ethanol to ethyl acetate was so selective
that no other oxidation products were yielded. With such a high selectivity, an
electrolyzer cell using Co3O4 nanosheets as the anode electrocatalyst and Ni-Mo
nanopowders as the cathode electrocatalyst has been successfully built for
ethanol reforming. The electrolyzer cell was readily driven by a 1.5 V battery to
achieve the effective production of both H2 and ethyl acetate. After the bulk
electrolysis, about 95% of ethanol was electrochemically reformed into ethyl
acetate. This work opens up new opportunities in designing a material system for
building unique devices to generate both hydrogen and high-value organics at room
temperature by utilizing electric energy from renewable sources.
PMID- 27610417
TI - Transport Properties of Polysulfide Species in Lithium-Sulfur Battery
Electrolytes: Coupling of Experiment and Theory.
AB - A comprehensive experimental and theoretical analysis of the isothermal transport
of species for the two model ternary-electrolytes with LiTFSI-Li2S4/dioxolane
(DOL)-dimethoxyethane (DME) and LiTFSI-Li2S6/DOL-DME formulations is presented.
An unambiguous picture of the polysulfide's mobility is set forth after a
detailed investigation of the macroscopic transference number and diffusion
coefficients. The new findings of incongruent diffusion for Li2S4 species and
high significance of cross-term diffusion coefficients reformulate a fledgling
view of the prevalent redox-shuttle phenomena. The practical implications of this
complex mechanism are discussed in detail.
PMID- 27610418
TI - Low Temperature Activation of Supported Metathesis Catalysts by Organosilicon
Reducing Agents.
AB - Alkene metathesis is a widely and increasingly used reaction in academia and
industry because of its efficiency in terms of atom economy and its wide
applicability. This reaction is notably responsible for the production of several
million tons of propene annually. Such industrial processes rely on inexpensive
silica-supported tungsten oxide catalysts, which operate at high temperatures
(>350 degrees C), in contrast with the mild room temperature reaction conditions
typically used with the corresponding molecular alkene metathesis homogeneous
catalysts. This large difference in the temperature requirements is generally
thought to arise from the difficulty in generating active sites (carbenes or
metallacyclobutanes) in the classical metal oxide catalysts and prevents broader
applicability, notably with functionalized substrates. We report here a low
temperature activation process of well-defined metal oxo surface species using
organosilicon reductants, which generate a large amount of active species at only
70 degrees C (0.6 active sites/W). This high activity at low temperature
broadens the scope of these catalysts to functionalized substrates. This
activation process can also be applied to classical industrial catalysts. We
provide evidence for the formation of a metallacyclopentane intermediate and
propose how the active species are formed.
PMID- 27610416
TI - Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with
Diverse Chemotherapeutics.
AB - Conventional chemotherapeutics remain essential treatments for most cancers, but
their combination with other anticancer drugs (including targeted therapeutics)
is often complicated by unpredictable synergies and multiplicative toxicities. As
cytotoxic anticancer chemotherapeutics generally function through induction of
apoptosis, we hypothesized that a molecularly targeted small molecule capable of
facilitating a central and defining step in the apoptotic cascade, the activation
of procaspase-3 to caspase-3, would broadly and predictably enhance activity of
cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1)
enhances cancer cell death induced by 15 different FDA-approved
chemotherapeutics, across many cancer types and chemotherapeutic targets. In
particular, the promising combination of PAC-1 and doxorubicin induces a
synergistic reduction in tumor burden and enhances survival in murine tumor
models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was
evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or
lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of
4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC
1 with doxorubicin resulted in no additional toxicity. On the basis of the mode
of action of PAC-1 and the high expression of procaspase-3 in many cancers, these
results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a
potent and general strategy to enhance therapeutic response.
PMID- 27610419
TI - Effects of Coenzyme Q10 on Skeletal Muscle Oxidative Metabolism in Statin Users
Assessed Using 31P Magnetic Resonance Spectroscopy: a Randomized Controlled
Study.
AB - OBJECTIVES: Statins partially block the production of coenzyme Q10 (CoQ10), an
essential component for mitochondrial function. Reduced skeletal muscle
mitochondrial oxidative capacity has been proposed to be a cause of statin
myalgia and can be measured using 31phosphorus magnetic resonance spectroscopy
(31P-MRS). The purpose of this study is to assess the effect of CoQ10 oral
supplementation on mitochondrial function in statin users using 31P-MRS.
DESIGN/SETTING: In this randomized, double-blind, placebo-controlled pilot study,
21 adults aged 47-73 were randomized to statin+placebo (n=9) or statin+CoQ10
(n=12). Phosphocreatine (PCr) recovery kinetics of calf muscles were assessed at
baseline (off statin and CoQ10) and 4 weeks after randomization to either
statin+CoQ10 or statin+placebo. RESULTS: Baseline and post-treatment PCr recovery
kinetics were assessed for 19 participants. After 4 weeks of statin+ CoQ10 or
statin+placebo, the overall relative percentage change (100*(baseline-follow
up)/baseline) in PCr recovery time was -15.1% compared with baseline among all
participants, (p-value=0.258). Participants randomized to statin+placebo (n=9)
had a relative percentage change in PCr recovery time of -18.9%, compared to
7.7% among participants (n=10) receiving statin+CoQ10 (p-value=0.448).
CONCLUSIONS: In this pilot study, there was no significant change in
mitochondrial function in patients receiving 4 weeks of statin+CoQ10 oral therapy
when compared to patients on statin+placebo.
PMID- 27610420
TI - Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function
Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case.
AB - Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood.
Recent neuroimaging studies found lowered baseline dopamine tone in the brains of
affected individuals that may place them at risk for Substance Use Disorder
(SUD). This is an observational case study of the potential for novel management
of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization
complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to
evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and
one hour following administration. The resultant z-scores, averaged across Eyes
Closed, Eyes Open and Working Memory conditions, increased for each frequency
band, in the anterior, dorsal and posterior cingulate regions, as well as the
right dorsolateral prefrontal cortex during Working Memory, with KB220z. These
scores are consistent with other human and animal neuroimaging studies that
demonstrated increased connectivity volumes in reward circuitry and may offer a
new approach to ADHD treatment. However, larger randomized trials to confirm
these results are required.
PMID- 27610421
TI - Urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes sustained
from transient acute kidney injury after general surgery.
AB - BACKGROUND: This prospective study tests the hypothesis that after general
surgery urinary NGAL can distinguish between sustained acute kidney injury (AKI),
typical of nephron damage, from transient AKI, commonly seen with hemodynamic
variation and prerenal azotemia. METHODS: Urine was collected in 510 patients
within 2-3 hr after general surgery and urinary NGAL was determined using ELISA.
Patients who met AKIN Stage 1 criteria of AKI were sub-classified into those with
sustained AKI (serum creatinine elevation for more than 3 days), and those with
transient AKI (serum creatinine elevation for less 3 days). RESULTS: Seventeen of
510 patients (3.3%) met the Stage 1 AKIN criteria within 48 hrs of surgery.
Elevations in serum creatinine were sustained in 9 and transient in 8 patients.
Urinary NGAL was significantly elevated only in patients with sustained AKI
(204.8+/-411.9 ng/dL); patients with transient AKI had urinary NGAL that was
indistinguishable from patients who did not meet AKIN criteria at all (30.8 +/
36.5 ng/dL vs. 31.9 +/-113 ng/dL). The area under the curve (AUC) of the receiver
operating characteristic (ROC) curve of urinary NGAL to predict sustained AKI was
0.85 [CI (95%): 0.773 to 0.929, p<0.001]. CONCLUSIONS: Urinary NGAL levels
measured 2-3 hr after surgery were able to distinguish the kinetics of creatinine
(sustained AKI vs transient AKI) over the subsequent week. Transient AKI is an
easily reversible state that is likely not associated with substantial tubular
injury and therefore NGAL release. Using AKIN criteria, both transient and
sustained AKI are classified as AKI even though our data demonstrates that they
are possibly different entities.
PMID- 27610422
TI - APOL1 Risk Alleles are Associated with More Severe Arteriosclerosis in Renal
Resistance Vessels with Aging and Hypertension.
AB - The increased risk of end-stage kidney disease (ESKD) among hypertensive African
Americans is partly related to APOL1 allele variants. Hypertension-associated
arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and
cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular
arteriosclerosis and ischemia, consists of focal global glomerulosclerosis
(FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found
with progression to ESKD, particularly in African Americans. This is a study of
arterionephrosclerosis in successfully APOL1 genotyped autopsy kidney tissue of
159 African Americans (61 no risk alleles, 68 one risk allele, 30 two risk
alleles) and 135 whites aged 18-89 years from a general population with no
clinical renal disease. Glomerulosclerosis was nearly exclusively FGGS with only
three subjects having FSGS-like lesions that were unrelated to APOL1 risk status.
For both races, in multivariable analysis, the dependent variables of
arteriosclerosis, glomerulosclerosis, and cortical fibrosis were all
significantly related to the independent variables of older age (P < 0.001) and
hypertension (P < 0.001). A relationship between APOL1 genotype and
arteriosclerosis was apparent only after 35 years of age when, for any level of
elevated blood pressure, more severe arteriosclerosis was found in the
interlobular arteries of 14 subjects with two APOL1 risk alleles when compared to
African Americans with none (n = 37, P = 0.02) or one risk alleles (n = 35, P =
0.02). With the limitation of the small number of subjects contributing to the
positive results, the findings imply that APOL1 risk alleles recessively augment
small vessel arteriosclerosis in conjunction with age and hypertension. FSGS was
not a significant finding, indicating that in the early stages of
arterionephrosclerosis, the primary pathologic influence of APOL1 genotype is
vascular rather than glomerular.
PMID- 27610423
TI - A Randomized Controlled Trial of a Mobile Clinical Decision Aid to Improve Access
to Kidney Transplantation: iChoose Kidney.
AB - Kidney transplantation is the preferred treatment for patients with end-stage
renal disease, as it substantially increases a patient's survival and is cost
saving compared to a lifetime of dialysis. However, transplantation is not
universally chosen by patients with renal failure, and limited knowledge about
the survival benefit of transplantation vs. dialysis may play a role. We created
a mobile application clinical decision aid called iChoose Kidney to improve
access to individualized prognosis information comparing dialysis and
transplantation outcomes. We describe the iChoose Kidney study, a randomized
controlled trial designed to test the clinical efficacy of a mobile health
decision aid among end-stage renal disease patients referred for kidney
transplantation at three large, diverse transplant centers across the U.S.
Approximately 450 patients will be randomized to receive either: (1) standard of
care or "usual" transplantation education, or (2) standard of care plus iChoose
Kidney. The primary outcome is change in knowledge about the survival benefit of
kidney transplantation vs. dialysis from baseline to immediate follow-up;
secondary outcomes include change in treatment preferences, improved decisional
conflict, and increased access to kidney transplantation. Analyses are also
planned to examine effectiveness across subgroups of race, socioeconomic status,
health literacy and health numeracy. Engaging patients in health care choices can
increase patient empowerment and improve knowledge and understanding of treatment
choices. If the effectiveness of iChoose Kidney has a greater impact on patients
with low health literacy, lower socioeconomic status, and minority race, this
decision aid could help reduce disparities in access to kidney transplantation.
PMID- 27610424
TI - Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood.
AB - BACKGROUND: Despite the highly replicated relationship between symptoms
associated with both alcohol and nicotine, little is known about this association
across time and exposure to both drinking and smoking. In the present study, we
evaluate if problems associated with alcohol use are related to emerging nicotine
dependence symptoms and whether this relationship varies from adolescence to
young adulthood, after accounting for both alcohol and nicotine exposure.
METHODS: The sample was drawn from the Social and Emotional Contexts of
Adolescent Smoking Patterns Study which measured smoking, nicotine dependence,
alcohol use and alcohol related problems over 6 assessment waves spanning 6
years. Analyses were based on repeated assessment of 864 participants reporting
some smoking and drinking 30 days prior to individual assessment waves. Mixed
effects regression models were estimated to examine potential time, smoking
and/or alcohol varying effects in the association between alcohol problems and
nicotine dependence. FINDINGS: Inter-individual differences in mean levels of
alcohol problems and within subject changes in alcohol problems from adolescence
to young adulthood were each significantly associated with nicotine dependence
symptoms over and above levels of smoking and drinking behaviour. This
association was consistent across both time and increasing levels of smoking and
drinking. CONCLUSIONS: Alcohol related problems are a consistent risk factor for
nicotine dependence over and above measures of drinking and smoking and this
association can be demonstrated from the earliest experiences with smoking in
adolescents, through the establishment of more regular smoking patterns across
the transition to young adulthood. These findings add to accumulating evidence
suggesting that smoking and drinking may be related through a mechanism that
cannot be wholly accounted for by exposure to either substance.
PMID- 27610425
TI - Solving Logistic Regression with Group Cardinality Constraints for Time Series
Analysis.
AB - We propose an algorithm to distinguish 3D+t images of healthy from diseased
subjects by solving logistic regression based on cardinality constrained, group
sparsity. This method reduces the risk of overfitting by providing an elegant
solution to identifying anatomical regions most impacted by disease. It also
ensures that consistent identification across the time series by grouping each
image feature across time and counting the number of non-zero groupings. While
popular in medical imaging, group cardinality constrained problems are generally
solved by relaxing counting with summing over the groupings. We instead solve the
original problem by generalizing a penalty decomposition algorithm, which
alternates between minimizing a logistic regression function with a regularizer
based on the Frobenius norm and enforcing sparsity. Applied to 86 cine MRIs of
healthy cases and subjects with Tetralogy of Fallot (TOF), our method correctly
identifies regions impacted by TOF and obtains a statistically significant higher
classification accuracy than logistic regression without and relaxed grouped
sparsity constraint.
PMID- 27610426
TI - Musculoskeletal injury in Australian general practice: 2000 to 2015.
PMID- 27610427
TI - Paediatric sports injuries.
AB - BACKGROUND: Paediatric sports injuries are common. Fortunately, most children
self-modulate their activity levels when injured until they recover, but some
will seek medical help. Injury pattern varies with age, mechanism and the chosen
sport. OBJECTIVE: The aim of this article is to give a general overview of some
of the more common paediatric sports injuries, including common patterns of
pathogenesis, the effects of growth and biomechanics on tissue load, and issues
particular to specific sports. DISCUSSION: The immature body has different
strength ratios of bone, muscle and tendon, and is constantly developing
coordination and body awareness, which are affected by growth and neurological
maturation. When planning the return to sport after an injury, the demands of the
chosen sport, hours and periodisation of training, and requirements of schooling
need to be considered. Bio-mechanical issues are best addressed early in
treatment to improve return-to-activity outcomes.
PMID- 27610428
TI - Concussive head injury in children and adolescents.
AB - BACKGROUND: Awareness of concussive head injury continues to grow, aided by
greater understanding of the neurobiological underpinnings of concussions and its
short-term and long-term consequences. Younger players who are in the midst of
their neurodevelopmental trajectory continue to be placed at risk; therefore,
more must be done to educate clinicians, parents, coaches and players alike in
this area. Our understanding of concussive injury is evolving and more integrated
models of care are being developed so as to provide patients with the holistic
model of care needed in the post-concussive context. OBJECTIVE: In this article,
we outline a contemporary perspective on concussion, and address an evidence
based approach to children and adolescents who have suffered a concussive injury.
DISCUSSION: Good clinical care of a patient with concussion by the primary care
physician is the best prevention of adverse outcomes. The ability of the primary
care physician to recognise when to treat and when to refer will be an important
agent for change in ?this field.
PMID- 27610429
TI - Clinical considerations for the ageing athlete.
AB - BACKGROUND: Many older people are participating in high-intensity activities and
sports. Clinicians need to be aware of the physiology of ageing relative to the
demands of higher intensity sport. Patient expectations, comorbidities and
medication use are important aspects to consider when advising the ageing athlete
appropriately. OBJECTIVE: This article highlights the important aspects of
maintaining a physically active lifestyle. For the ageing athlete, there are
differing needs as well as risks associated with higher intensity physical
activity. This article will outline how to cater for these needs and minimise the
potential risks. DISCUSSION: Appreciating the importance of physical activity as
a major public health intervention is essential for all clinicians. Ensuring that
the ageing athlete is able to participate safely and optimally in higher
intensity physical activity is an increasing expectation.
PMID- 27610430
TI - Allergic reactions to insulin detemir in women with gestational diabetes
mellitus.
PMID- 27610431
TI - Dry mouth: Xerostomia and salivary gland hypofunction.
AB - BACKGROUND: Mouth dryness may present as salivary gland hypofunction (SGH),
xerostomia or both. It is considered one of the most underappreciated,
underdiagnosed and undermanaged oral health conditions. Despite its common
presentation and adverse impact on life quality, it is also generally poorly
understood. Increased awareness of the condition is important in addressing these
problems. OBJECTIVE: This article discusses SGH and xerostomia, and the
associated intra-oral and extra-oral implications. It also summarises currently
available management approaches and the evidence behind them. DISCUSSION: SGH and
xerostomia are complex problems. None of the currently available management
approaches are entirely satisfactory. Addressing the causative or contributing
factors is therefore paramount. While oral health complaints are generally left
up to the dental professional to manage, the nature of mouth dryness necessitates
increased dialogue between the dental and ?medical professions to ensure optimal
patient care.
PMID- 27610432
TI - Otalgia.
AB - BACKGROUND: Otalgia is frequently seen in general practice. It can be broadly
divided into primary otalgia, which includes the diseases occurring largely
within the ear, or secondary otalgia, which is pain referred to the ear by
travelling along cranial nerves that supply both the ear and referred region. The
causes of secondary otalgia may require more extensive examination and
investigation to define the aetiology. OBJECTIVE: The aims of this article are to
outline the most common causes of otalgia seen in general practice, and provide a
pragmatic approach to initial assessment and deciding when to refer for
specialist review. DISCUSSION: The most common cause of primary otalgia is
infection. Other causes require a greater index of suspicion. Specialist referral
could be made if there are complications of primary otalgia or if a secondary
cause needs to be excluded in a patient with a normal otology examination.
PMID- 27610433
TI - Management of urinary incontinence in residential care.
AB - BACKGROUND: Urinary incontinence is prevalent in residential care and rates are
expected to increase with the ageing population in Australia. It contributes to
poor quality of life (QoL), functional impairments in activities of daily living,
and deterioration of mental and sexual health. Management depends on the type of
incontinence, its aetiology, the severity of symptoms, the effects on QoL, and
patient factors. Treatment options include active treatment and passive
containment. However, not all active treatment options are feasible in
residential care. There is little evidence to advise on standard best practice.
OBJECTIVE: The aims of this article are to review treatment options for urinary
incontinence in residential care, feasibility of service delivery and challenges
associated with this. DISCUSSION: A greater understanding of the issues
surrounding the management of urinary incontinence in residential care is
required to deliver satisfactory patient-centred care on a consistent basis.
PMID- 27610434
TI - An unusual case of vertigo.
PMID- 27610435
TI - A circle of silence: The attitudes of patients older than 65 years of age to
ceasing long-term sleeping tablets.
AB - BACKGROUND: Nocturnal benzodiazepines have a significant negative health impact
on the elderly, yet they continue to be used. OBJECTIVE: The aim of this study
was to assess elderly patients' use and knowledge of nocturnal benzodiazepines,
and their attitudes to cessation. METHODS: Semi-structured telephone interviews
were conducted with elderly patients (n = 17) from four general practices in
Australia. RESULTS: Our study found that the initiation of benzodiazepine use was
often at a time of stress for the patient. Long-term use was not in-tended, and
patients conveyed poor awareness of the side effects and addictive potential of
benzodiazepines. Patients' perceived attitudes of their general practitioner (GP)
to prescribing benzodiazepines and lack of awareness of alternative therapies
were key to continuation. Confounding factors such as pain often contributed to
sleep disturbance. Many patients expressed a willingness to cease nocturnal
benzodiazepine use. DISCUSSION: These data assist in raising GPs' awareness of
patients' attitudes to cessation of nocturnal benzodiazepine use. More time spent
with patients presenting for repeat prescriptions, explaining side effects,
discussing alternative options and investigating reasons for not sleeping could
reduce benzodiazepine use among the elderly.
PMID- 27610436
TI - Consumer awareness, satisfaction, motivation and perceived benefits from using an
after-hours GP helpline - A mixed methods study.
AB - BACKGROUND: The 'after hours GP helpline' (AGPH) was added to the nurse triage
and advice services in Australia in July 2011 with the intention of improving
access to general practitioner (GP) advice in the after-hours period. OBJECTIVE:
The objectives of the article are to examine consumer awareness, satisfaction,
motivation for use and perceived benefits of using the AGPH. METHODS: A mixed
methods approach used secondary data on population awareness and caller
satisfaction, and an in-depth qualitative study of consumers. RESULTS: Awareness
of the service was low but satisfaction was high. Users called the service
because they did not know what to do, were afraid and/or could not access a
health service after hours. Users derived reassurance and increased confidence in
managing their health. DISCUSSION: A conceptual model identifying three
experiential domains of dependence, access and health literacy illustrates the
relationship between motivation for use and perceived benefits. The model may
help to target the service to those who will benefit most.
PMID- 27610437
TI - Test result audit and feedback (TRAFk) as a supervision method for rational test
ordering in general practice training.
AB - BACKGROUND: The use of medical investigations is increasing, with most testing
occurring in primary care. The interpretation of test results is challenging for
general practice registrars. Additionally, emerging evidence suggests that over
testing is a significant problem and has the potential for patient harm. Test
result audit and feedback (TRAFk) is a teaching and supervision method in general
practice training, but no previous studies have investigated its utility.
OBJECTIVE: The objective of this article is to describe the outcomes of an
educational intervention for general practice supervisors on TRAFk. METHODS: We
developed and delivered a workshop to general practice supervisors and
administered pre- and post-workshop surveys. RESULTS: Of the 54 supervisors who
participated in the study, a substantial proportion (79.6%) used TRAFk after the
workshop. Participants highly rated the method across a range of supervision
areas, including clinical reasoning, test ordering quality and patient safety.
DISCUSSION: Our findings reinforce the educational utility of this supervision
method in general practice training for the teaching and assessment of
registrars.
PMID- 27610438
TI - Contraceptive choices and sexual health of Japanese women living in Australia: A
brief report from a qualitative study.
AB - BACKGROUND: There is a lack of research focused specifically on the contraceptive
and sexual health practices of Japanese women living in Australia. OBJECTIVE:
This paper reports findings from a cohort of migrant Japanese women who
participated in a study of Australian women's understanding and experience of
contraceptives. METHODS: In-depth, open-ended interviews were conducted between
August 2012 and June 2013 in New South Wales. Audio-recorded interviews of seven
Japanese women were transcribed verbatim and analysed thematically. RESULTS: The
four prominent themes were the condom and withdrawal methods, varying attitudes
to contraceptive practices, discussing contraception and sexual issues with
general practitioners (GPs), and the unspoken topic of sexually transmissible
infections (STIs). DISCUSSION: Japanese migrants tend to choose the condom and
withdrawal methods, which they perceive to be 'standard practice' in Japan. A
greater understanding by Australian GPs of Japanese women's attitudes to
contraception and sexual health issues could enhance the sexual health of
Japanese women.
PMID- 27610439
TI - What is happening to patients who have had polio? The role of the patient in
assessment and management.
PMID- 27610440
TI - Antenatal care in Australian general practice.
PMID- 27610441
TI - Nutrition care by general practitioners: Enhancing women's health during and
after pregnancy.
AB - BACKGROUND: The importance of healthy dietary behaviours during pregnancy and
after birth is well recognised given the short-term and long-term effects on the
health of mothers and infants. Pregnancy is an ideal time to implement health
behaviour changes, as women are receptive to health messages at this time. The
majority of pregnant women have regular, ongoing contact with general
practitioners (GPs), particularly during early pregnancy. OBJECTIVE: This paper
provides an overview of the latest evidence regarding the nutrition requirements
of women during and after birth, and describes simple ways that GPs can
incorporate brief, effective nutrition care into standard consultations.
DISCUSSION: Two approaches for enhancing the nutrition care provided by GPs are
presented. These approaches are for GPs to feel confident in raising the topic of
nutrition in standard consultations and being equipped with effective, evidence
based messages that can be incorporated into consultations. Collectively, these
approaches promote healthy dietary behaviours for intergenerational benefits.
PMID- 27610442
TI - There from the start: Men and pregnancy.
AB - BACKGROUND: The author's clinical experience with fathers-to-be during pregnancy
has highlighted the importance of paternal presence in family and clinical
settings. This has motivated the steady development of his clinical practice
towards whole-family care by reaching out to fathers and fathers-to-be.
OBJECTIVE: This article summarises the clinical experience of a perinatal
psychiatrist and clinical specialist in fathers' mental health, around men's
lives during pregnancy. The article also presents commonly observed clinical
patterns and makes suggestions for clinicians seeking to enhance the care of
these men and their families. DISCUSSION: Three key ideas gleaned from working
with men in pregnancy are: occult perinatal mental health issues in men that have
an impact on family wellbeing; seeking gender equity in co-parenting by
acknowledging mothers' and fathers' '50-50' responsibility for the 'psychological
birth' of a child; and strengths-based engagement of men as a men's health
opportunity. Further resources are provided.
PMID- 27610443
TI - Overcoming challenges faced by breastfeeding mothers.
AB - BACKGROUND: Women who are breastfeeding often consult their general practitioner
(GP) with concerns about nipple and breast pain, or the adequacy of their milk
supply. Common concerns for their breastfed infant include slow weight gain,
'fussiness' with breastfeeding and 'funny stools'. OBJECTIVE: This article offers
suggestions for clinicians to support breastfeeding women and their infants.
DISCUSSION: Good attachment to the breast is important to reduce nipple pain and
trauma, and to ensure adequate breast drainage and ongoing milk supply. Other
causes of nipple pain include vasospasm, dermatitis and infection. Breast pain
may be due to blocked ducts, mastitis or abscess. Very early mastitis may be
treated by improved emptying. Slow weight gain in a breastfed infant may indicate
a medical problem or low supply of breast milk. Some infants have breastfeeding
challenges because they are small or premature, or from anatomical issues
affecting feeding. In such cases, further help from a lactation consultant may be
beneficial.
PMID- 27610444
TI - Paediatric urinary tract infections: Diagnosis and treatment.
AB - BACKGROUND: Urinary tract infections (UTIs) commonly occur in children. An
estimated 8% of girls and 2% of boys will have at least one episode by seven
years of age. Of these children, 12-30% will experience recurrence within one
year. Australian hospital admission records indicate that paediatric UTIs
represent 12% of all UTI hospital admissions. OBJECTIVE: The aim of this article
is to review the pathogenesis, clinical assessment and management of UTIs, and
prevention strategies in children. DISCUSSION: Clinically, paediatric UTI
presentations are challenging because symptoms are vague and variable. Young
infants may present with sepsis or fever and lack specific symptoms, whereas
older children present with classical features such as dysuria, frequency and
loin pain. Early diagnosis with appropriate urine specimen collection techniques,
investigations and treatment is necessary for prevention of renal damage and
recurrence. Effective, evidence-based investigations and treatment options are
available, and physicians should feel confident in identifying and managing
paediatric UTIs.
PMID- 27610445
TI - Managing nausea and vomiting in pregnancy in a primary care setting.
AB - ERRATUM.
PMID- 27610446
TI - Smoking cessation in people with alcohol and other drug problems.
AB - BACKGROUND: People who consume alcohol and other drugs are at particularly high
risk of harm from smoking, yet tobacco use is commonly neglected in this patient
group. OBJECTIVE: The objectives of this article are to increase awareness of the
high risk of tobacco-related harm in people who consume alcohol and other drugs,
identify the barriers to quitting and provide practical guidelines to assist
quitting. DISCUSSION: People who are dependent on alcohol and other drugs are far
more likely to die from a smoking-related illness than from their other drugs.
Most are motivated to quit smoking; however, their quit rates are lower than in
the general population. Substance users who also smoke can usually be treated
with similar behavioural and pharmacological treatments as others who smoke, but
generally require more intensive and longer treatment. Quitting smoking at the
same time as undergoing other drug treatment does not undermine drug treatment
outcomes and may improve them. Smoking cessation should be integrated into the
routine care of patients who consume alcohol and other drugs.
PMID- 27610447
TI - Surgery for adult patients with obstructive sleep apnoea: A review for general
practitioners.
AB - BACKGROUND: Obstructive sleep apnoea (OSA) is a complex disease process that
involves collapse of the upper airway during sleep and subsequent reduction or
cessation of airflow. Continuous positive airway pressure (CPAP) is the primary
treatment for OSA and is the recommended first-line treatment for patients with
moderate-to-severe forms of the disease. However, some patients are unable to
tolerate CPAP or are unwilling to accept it as a form of permanent management. In
these cases, surgical management aimed at addressing anatomical obstruction may
be useful and warranted. OBJECTIVE: This article presents an overview of the
surgical options available for OSA. The review also describes a useful approach
for selecting appropriate patients for surgery. DISCUSSION: On the basis of an
OSA model that accounts for observed increased risk of stroke, cardiovascular
disease and motor vehicle accidents, there is evidence to support that surgery is
beneficial and cost-effective for patients with severe OSA who are intolerant of
CPAP. There are many surgical options available for OSA.
PMID- 27610448
TI - Widespread rash after throat infection.
PMID- 27610449
TI - Identifying Risk for Diabetes in Adolescence (IRDA): A pilot study in general
practice.
AB - BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) in adolescents is
increasing, particularly among those in lower socioeconomic areas, and of
Aboriginal and Torres Strait Islander, Pacific Islander and Asian ethnicities.
OBJECTIVE: The aim of this article is to test the acceptability and feasibility
of a brief screening program for T2DM risk factors in young adolescents in a
general practice in a high-risk, low socioeconomic area. METHODS: Twenty-two
adolescents participated in the program over three months. Anthropometric
measures, glycated haemoglobin (HbA1c), lipids, diet and exercise data were
collected. Parents completed a short survey. Data were summarised using
descriptive statistics and frequency graphs, and brief qualitative data on
acceptability were also collected. RESULTS: Nineteen out of the 22 adolescents
had at least one risk factor for developing T2DM and 11 had three or more risk
factors. Thirty-two per cent of the participants had a parent currently living
with T2DM and five out of 22 had an HbA1c level >5.8%, suggesting increased risk
for T2DM. DISCUSSION: Screening was feasible and acceptable in this setting. The
findings suggest a need for extended screening in the future.
PMID- 27610450
TI - Discussing alcohol and cancer with patients: Knowledge and practices of general
practitioners in New South Wales and South Australia.
AB - BACKGROUND: Alcohol is associated with several cancers; however, the Australian
community has low awareness of the link between alcohol consumption and cancer.
Little information exists regarding when and why general practitioners (GPs)
discuss alcohol with patients. OBJECTIVE: The objective of this article is to
explore GPs' attitudes and practices when discussing alcohol with patients. This
includes awareness of alcohol recommendations and evidence of the alcohol-cancer
link, and discussion around barriers and enablers to encouraging patients'
alcohol behaviour change. RESULTS: GPs did not routinely ask patients about their
alcohol consumption or advise on drinking recommendations. Many had a broad
understanding of alcohol as a cancer risk factor, but knowledge of the causal
mechanisms and current evidence was limited. DISCUSSION: GPs are trusted health
advisers. Providing them with up-to-date evidence on the alcohol-cancer link and
drinking recommendations may encourage routine patient screening of alcohol
consumption and delivery of simple education on the harms of long-term drinking.
PMID- 27610451
TI - Setting up a domestic violence telephone helpline for general practitioners in
Australia: What exists and what works?
AB - BACKGROUND: Domestic violence is a global health issue. The World Health
Organization (WHO) recommends training health professionals to respond
appropriately to victims of domestic violence. Despite those who experience
domestic violence attending general practice, general practitioners (GPs) receive
little training in managing this issue. Helplines predominantly exist to support
the general public and patients; however, few exist for GPs, and there are none
regarding domestic violence. OBJECTIVE: This article explores how helplines can
support GPs in the management of patients who have experienced domestic violence.
METHODS: A scoping review of helplines targeting GPs was used in this study.
RESULTS: Few helplines target health professionals and limited evaluations on
these helplines have been undertaken. Health professional helplines cover broad
specialist fields, and health professionals value access to specialists.
Helplines are educational and increase the confidence of health professionals in
providing quality patient care. Key challenges include helpline awareness and
timely support. DISCUSSION: Developing a domestic violence helpline for GPs is
unexplored, but there is potential for education and improved response to
patients. Helpline workers need tailored training to respond to health
professionals' complex, specialist needs. These helplines need extensive
marketing to ensure uptake and funding.
PMID- 27610452
TI - A diabetes-specific e-mental health tool: Development, acceptability and outcomes
of a feasibility study.
AB - BACKGROUND: Psychological problems are frequently comorbid with diabetes and can
be complex and time consuming to manage in general practice. They can also
complicate diabetes management. OBJECTIVE: This pre-post, mixed-methods study
examined whether a diabetes-specific online module, integrated into an existing e
mental health program, is acceptable to patients and helps to improve
psychological wellbeing. METHODS: The study was conducted in three stages. First,
qualitative information was obtained from consumers and practitioners to inform
module content. Second, clinical content for the module was developed, including
psychoeducational material and clinical content. In the final stage,
acceptability and feasibility was evaluated in a group of patients with diabetes.
RESULTS: Patients' satisfaction with and acceptance of the module was high.
Significant improvement in mental health and diabetes outcomes was also observed.
DISCUSSION: Preliminary evidence suggests that the online diabetes module may be
a useful psychological support for patients with diabetes. Further controlled
investigation is warranted.
PMID- 27610453
TI - A clinical placement program for primary care professionals at a comprehensive
cancer centre.
AB - BACKGROUND: There is a growing number of cancer survivors and increasing interest
in models of patient-centred shared care between oncology and primary care.
OBJECTIVE: The objective of this article was to investigate whether a placement
program for general practitioners (GPs) and general practice nurses (GPNs) was
feasible, of clinical and professional value, and facilitated knowledge and
skills transfer. METHODS: The program recruited GPs and GPNs to complete a 10
hour placement at a cancer centre. Participants completed pre-placement and post
placement semi-structured interviews. RESULTS: The participants for the study
included 16 GPs, 12 GPNs and nine oncologists. All generalists reported that the
program's learning outcomes, personal learning needs and relevance to practice
were 'entirely' or 'partially' met All would recommend the program and could
identify knowledge and skills transfer; however, learning was largely by
observation rather than participation. Learning opportunities were skewed towards
generalists. Participants showed enthusiasm to address the challenges of
providing shared care. DISCUSSION: The clinical placement program was feasible
and highly regarded.
PMID- 27610454
TI - Polyphosphate delays fibrin polymerisation and alters the mechanical properties
of the fibrin network.
AB - Polyphosphate (polyP) binds to fibrin(ogen) and alters fibrin structure,
generating a heterogeneous network composed of 'knots' interspersed by large
pores. Here we show platelet-derived polyP elicits similar structural changes in
fibrin and examine the mechanism by which polyP alters fibrin structure.
Polymerisation of fibrinogen with thrombin and CaCl2 was studied using spinning
disk confocal (SDC) microscopy. PolyP delayed fibrin polymerisation generating
shorter protofibrils emanating from a nucleus-type structure. Consistent with
this, cascade blue-polyP accumulated in fibrin 'knots'. Protofibril formation was
visualized by atomic force microscopy (AFM) +/- polyP. In the presence of polyP
abundant monomers of longer length were visualised by AFM, suggesting that polyP
binds to monomeric fibrin. Shorter oligomers form in the presence of polyP,
consistent with the stunted protofibrils visualised by SDC microscopy. We
examined whether these structural changes induced by polyP alter fibrin's
viscoelastic properties by rheometry. PolyP reduced the stiffness (G') and
ability of the fibrin network to deform plastically G'', but to different
extents. Consequently, the relative plastic component (loss tangent (G''/G')) was
61 % higher implying that networks containing polyP are less stiff and more
plastic. Local rheological measurements, performed using magnetic tweezers,
indicate that the fibrin dense knots are stiffer and more plastic, reflecting the
heterogeneity of the network. Our data show that polyP impedes fibrin
polymerisation, stunting protofibril growth producing 'knotted' regions, which
are rich in fibrin and polyP. Consequently, the mechanical properties of the
fibrin network are altered resulting in clots with overall reduced stiffness and
increased ability to deform plastically.
PMID- 27610456
TI - Evaluation and Stability of PEDOT Polymer Electrodes for Li-O2 Batteries.
AB - Lithium-air (O2) batteries have shown great promise because of their high
gravimetric energy density-an order of magnitude greater than Li-ion-but
challenges such as electrolyte and electrode instability have led to poor
capacity retention and low cycle life. Positive electrodes such as carbon and
inorganic metal oxides have been heavily explored, but the degradation of carbon
and the limited surface area of the metal oxides limit their practical use. In
this work, we study the electron-conducting polymer poly(3,4
ethylenedioxythiophene) (PEDOT) and show it can support oxygen reduction to form
Li2O2 in a nonaqueous environment. We also propose a degradation mechanism and
show that the formation of sulfone functionalities on the PEDOT surface and
cleavage of the polymer repeat unit impairs electron conductivity and leads to
poor cycling. Our findings are important in the search for new Li-O2 electrodes,
and the physical insights provided are significant and timely.
PMID- 27610455
TI - Sulfated Hyaluronan Alters the Interaction Profile of TIMP-3 with the Endocytic
Receptor LRP-1 Clusters II and IV and Increases the Extracellular TIMP-3 Level of
Human Bone Marrow Stromal Cells.
AB - Sulfated glycosaminoglycans (sGAGs) modulate cellular processes via their
interaction with extracellular matrix (ECM) proteins. We revealed a direct
binding of tissue inhibitor of metalloproteinase-3 (TIMP-3) to the endocytic
receptor low-density lipoprotein receptor-related protein (LRP-1) clusters II and
IV using surface plasmon resonance. Sulfated hyaluronan (sHA) and chondroitin
sulfate (sCS) derivatives interfered with TIMP-3/LRP-1 complex formation in a
sulfation-dependent manner stronger than heparin. Electrostatic potential
calculations suggested a competition between negatively charged GAGs and highly
negatively charged complement-like domains of LRP-1 for the binding to a
positively charged area of TIMP-3 as an underlying mechanism. In vitro studies
revealed increased amounts of pericellular TIMP-3 in the presence of sHA as a
consequence of the blocked protein uptake. GAG derivatives as part of
biomaterials might post-translationally modulate TIMP-3 levels stronger than
native GAGs, thus exhibiting catabolic effects on the ECM, which could prevent
extensive pathological matrix degradation and promote wound healing.
PMID- 27610457
TI - Femtomole Infrared Spectroscopy at the Electrified Metal-Solution Interface.
AB - Characterization of surface adsorbed species using infrared (IR) spectroscopy
provides valuable information concerning interfacial chemical and physical
processes. However, in situ infrared studies of surface areas approaching the IR
diffraction limit, such as micrometer scale electrodes, require a hitherto
unrealized means to obtain high signal-to-noise (S/N) spectra from femtomole
quantities of adsorbed molecules. A major methodological breakthrough is
described that couples the high brilliance of synchrotron-sourced infrared
microscopy with attenuated total reflection surface enhanced infrared
spectroscopy (ATR-SEIRAS). The method is shown to allow the spectral measurement
of a monolayer of 4-methoxypyridine (MOP) adsorbed on a surface enhancing gold
film electrode under fully operational electrochemistry conditions. A factor of
15 noise improvement is achieved with small apertures using synchrotron IR
relative to a thermal IR source. The very low noise levels allow the measurement
of high quality IR spectra of 2.5 fmol of molecules confined to a 125 MUm2 beam
spot.
PMID- 27610458
TI - Medical countermeasures for unwanted CBRN exposures: part II radiological and
nuclear threats with review of recent countermeasure patents.
AB - INTRODUCTION: The global threat of a chemical, biological, radiological, or
nuclear (CBRN) disaster is an important priority for all government agencies
involved in domestic security and public health preparedness.
Radiological/nuclear (RN) attacks or accidents have become a larger focus of the
United States Food and Drug administration (US FDA) over time because of their
increased likeliness. Clinical signs and symptoms of a developing acute radiation
syndrome (ARS) are grouped into three sub-syndromes named for the dominant organ
system affected, namely the hematopoietic (H-ARS), gastrointestinal (GI-ARS), and
neurovascular systems. The availability of safe and effective countermeasures
against radiological/nuclear threats currently represents a significant unmet
medical need. Areas covered: This article reviews the development of RN threat
medical countermeasures and highlights those specific countermeasures that have
been recently patented and approved following the FDA Animal Rule. Patents for
such agents from 2015 have been presented. Expert opinion: Two granulocyte colony
stimulating factor (G-CSF)-based radiation countermeasures (Neupogen(r) (Amgen,
Thousand Oaks, CA) and Neulasta(r) (Amgen, Thousand Oaks, CA)) have recently been
approved by the FDA for treatment of H-ARS and both these agents are
radiomitigators, used after radiation exposure. To date, there are no FDA
approved radioprotectors for ARS.
PMID- 27610459
TI - Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute
Myeloid Leukemia in a Korean Population.
AB - AIMS: Some members of the poly ADP-ribose polymerase (PARP) protein family have
been regarded as targets for the therapeutic inhibition of cancer. Among these
PARP genes, poly ADP-ribose polymerase family, member 15 (PARP15) is a candidate
gene for cancer development due to its ability to regulate gene transcription and
its reported association with apoptosis. The current study investigated the
possible association between PARP15 single-nucleotide polymorphisms and the risk
of acute myeloid leukemia (AML). In addition, we analyzed the effects of the
PARP15 polymorphisms on the clinical phenotypes associated with cytosine
arabinose (AraC) chemotherapy in AML patients. METHODS: Ten PARP15 polymorphisms
were genotyped via TaqMan assay in a total of 344 Korean subjects, including 103
AML patients and 241 normal controls. The genetic effects of the polymorphisms on
the risk of AML and the clinical phenotypes were analyzed using Statistical
Analysis System (SAS) software. RESULTS: The results from a Cox regression
analysis for overall survival revealed that two polymorphisms were associated
with increased overall survival and the signal for rs17208928 was retained after
correcting for multiple tests (pcorr < 0.05). CONCLUSIONS: These results suggest
the possibility that the PARP15 gene may be a potential therapeutic target in AML
patients although much larger scale studies are needed for validation.
PMID- 27610460
TI - Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained
and Atomistic Molecular Dynamics Simulations.
AB - Gangliosides are glycolipids in which an oligosaccharide headgroup containing one
or more sialic acids is connected to a ceramide. Gangliosides reside in the outer
leaflet of the plasma membrane and play a crucial role in various physiological
processes such as cell signal transduction and neuronal differentiation by
modulating structures and functions of membrane proteins. Because the detailed
behavior of gangliosides and protein-ganglioside interactions are poorly known,
we investigated the interactions between the gangliosides GM1 and GM3 and the
proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics
simulations and potential of mean force calculations at both coarse-grained (CG)
and atomistic levels. In atomistic simulations, on the basis of the GROMOS force
field, ganglioside aggregation appears to be a result of the balance between
hydrogen bond interactions and steric hindrance of the headgroups. GM3 clusters
are slightly larger and more ordered than GM1 clusters due to the smaller
headgroup of GM3. The different structures of GM1 and GM3 clusters from atomistic
simulations are not observed at the CG level based on the Martini model, implying
a difference in driving forces for ganglioside interactions in atomistic and CG
simulations. For protein-ganglioside interactions, in the atomistic simulations,
GM1 lipids bind to specific sites on the AQP1 surface, whereas they are depleted
from WALP23. In the CG simulations, the ganglioside binding sites on the AQP1
surface are similar, but ganglioside aggregation and protein-ganglioside
interactions are more prevalent than in the atomistic simulations. Using the
polarizable Martini water model, results were closer to the atomistic
simulations. Although experimental data for validation is lacking, we proposed
modified Martini parameters for gangliosides to more closely mimic the sizes and
structures of ganglioside clusters observed at the atomistic level.
PMID- 27610461
TI - Quality of Care for HIV/AIDS and for Primary Prevention by HIV Specialists and
Nonspecialists.
AB - The role of HIV specialists in providing primary care to persons living with
HIV/AIDS is evolving, given their increased incidence of comorbidities.
Multivariate logit analysis compared compliance with sentinel preventive
screening tests and interventions among publicly insured Californians with and
without access to HIV specialists in 2010. Quality-of-care indicators [visit
frequency, CD4 and viral load (VL) assessments, influenza vaccine, tuberculosis
(TB) testing, lipid profile, glucose blood test, and Pap smears for women] were
related to patient characteristics and provider HIV caseload. There were 9377
adult Medicare enrollees (71% also had Medicaid coverage) and 2076 enrollees with
only Medicaid coverage. Adjusted for patient characteristics, patients seeing
providers with greater HIV caseloads (>50 HIV patients) were more likely to meet
visit frequency guidelines in both Medicare [98%; confidence interval (CI 97.5
98.2) and Medicaid (97%; CI 96.2-98.0), compared to 60% (CI 57.1-62.3) and 45%
(CI 38.3-50.4), respectively, seeing providers without large HIV caseloads (p <
0.001). Patients seeing providers with larger caseloads were significantly more
likely to have CD4 (p < 0.001), VL (p < 0.001), and TB testing (p < 0.05). A
larger percentage of patients seeing large-volume Medicare providers received
influenza vaccinations. Provider caseload was unrelated to lipid or glucose
assessments or Pap Smears for women. Patients with access to large-volume
providers were more likely to meet clinical guidelines for visits, CD4, VL,
tuberculosis testing, and influenza vaccinations, and were not less likely to
receive primary preventive care. Substantial insufficiencies remain in both
monitoring to assess viral suppression and in preventive care.
PMID- 27610462
TI - Potential Impact of Integrating HIV Surveillance and Clinic Data on Retention-in
Care Estimates and Re-Engagement Efforts.
AB - Retention in care is essential to the health of people living with HIV and also
for their communities. We sought to quantify the value of integrating HIV
surveillance data with clinical records for improving the accuracy of retention
in-care estimates and the efficiency of efforts to re-engage out-of-care
patients. Electronic medical records (EMRs) of HIV+ patients >=18 years old from
a public, hospital-based clinic in Minneapolis, MN between 2008 and 2014 were
merged with state surveillance data on HIV-related laboratory tests, out-of-state
relocation, and mortality. We calculated levels of retention and estimated the
number of required case investigations to re-engage patients who appeared to be
out of care over the study period with and without surveillance data integration.
Retention was measured as the proportion of years in compliance with Health
Resources and Services Administration (HRSA) guidelines (two clinical encounters
>90 days apart annually) and the proportion of patients experiencing a gap in
care >12 months. With data integration, retention estimates improved from an
average HRSA compliance of 70.3% using EMR data alone to 77.5% with surveillance
data, whereas the proportion of patients experiencing a >12-month gap in care
decreased from 45.0% to 34.4%. If case investigations to re-engage patients were
initiated after a 12-month gap in care, surveillance data would avoid 330 (29.3%)
investigations over the study period. Surveillance data integration improves the
accuracy of retention-in-care estimates and would avert a substantial number of
unnecessary case investigations for patients who appear to be out of care but, in
fact, receive care elsewhere or have died.
PMID- 27610463
TI - Prevalence and Correlates of HIV Infection and HIV Testing Among Transgender
Women in Jamaica.
AB - Transgender women are overrepresented in the Caribbean HIV epidemic. The study
objective was to examine correlates of HIV infection and HIV testing among
transgender women in Jamaica. We implemented a cross-sectional survey with
transgender women in Kingston and Ocho Rios, Jamaica. We conducted multivariable
logistic regression to identify factors associated with HIV testing and HIV
infection. Among 137 transgender women [mean age 24.0; standard deviation (SD)
5.5], three-quarters (n = 103, 75.7%) had received an HIV test. Of these, one
quarter (n = 26, 25.2%) were HIV positive. In multivariable analyses, HIV testing
was associated with: perceived HIV risk [adjusted odds ratio (AOR) 2.42,
confidence interval (CI) 1.36-4.28], depression (AOR 1.34, CI 1.01-1.77), forced
sex (AOR 3.83, CI 1.42-10.35), physical abuse (AOR 4.11, CI 1.44-11.72),
perceived transgender stigma (AOR 1.23, 1.06-1.42), having a healthcare provider
(AOR 5.89, CI 1.46-23.77), and lower HIV-related stigma (AOR 0.96, CI 0.92-0.99),
incarceration (AOR 0.28, CI 0.10-0.78), and drug use (AOR 0.74, CI 0.58-0.95).
HIV infection was associated with the following: homelessness (AOR 5.94, CI 1.27
27.74), perceived HIV risk (AOR 1.67, CI 1.02-2.72), depression (AOR 1.39, CI
1.06-1.82), STI history (AOR 56.79, CI 5.12-630.33), perceived (AOR 1.26, CI 1.06
1.51) and enacted (AOR 1.16, CI 1.04-1.29) transgender stigma, forced sex (AOR
4.14, CI 1.49-11.51), physical abuse (AOR 3.75, CI 1.39-10.12), and lower self
rated health (AOR 0.55, CI 0.30-0.98) and social support (AOR 0.79, CI 0.64
0.97). Transgender women in Jamaica experience high HIV infection rates and
suboptimal HIV testing. Combination HIV prevention approaches should address
transgender women's social and structural vulnerabilities.
PMID- 27610465
TI - Catalytic Proton Coupled Electron Transfer from Metal Hydrides to Titanocene
Amides, Hydrazides and Imides: Determination of Thermodynamic Parameters Relevant
to Nitrogen Fixation.
AB - The hydrogenolysis of titanium-nitrogen bonds in a series of
bis(cyclopentadienyl) titanium amides, hydrazides and imides by proton coupled
electron transfer (PCET) is described. Twelve different N-H bond dissociation
free energies (BDFEs) among the various nitrogen-containing ligands were measured
or calculated, and effects of metal oxidation state and N-ligand substituent were
determined. Two metal hydride complexes, (eta5-C5Me5)(py-Ph)Rh-H (py-Ph = 2
pyridylphenyl, [Rh]-H) and (eta5-C5R5)(CO)3Cr-H ([Cr]R-H, R= H, Me) were
evaluated for formal H atom transfer reactivity and were selected due to their
relatively weak M-H bond strengths yet ability to activate and cleave molecular
hydrogen. Despite comparable M-H BDFEs, disparate reactivity between the two
compounds was observed and was traced to the vastly different acidities of the M
H bonds and overall redox potentials of the molecules. With [Rh]-H, catalytic
syntheses of ammonia, silylamine and N,N-dimethylhydrazine have been accomplished
from the corresponding titanium(IV) complex using H2 as the stoichiometric H atom
source. The data presented in this study provides the thermochemical foundation
for the synthesis of NH3 by proton coupled electron transfer at a well-defined
transition metal center.
PMID- 27610464
TI - Good Health and Moral Responsibility: Key Concepts Underlying the Interpretation
of Treatment as Prevention in South Africa and Zambia Before Rolling Out
Universal HIV Testing and Treatment.
AB - Gauging community responses to the WHO 2015 recommendation to provide
antiretroviral treatment (ART) to all people living with HIV (PLHIV) is critical.
There is limited qualitative evidence on the acceptability of this Universal Test
and Treat (UTT) strategy or community understanding of the impact of ART on
reducing HIV transmission, promoted as Treatment as Prevention (TasP). This
article explores early understanding of UTT and TasP in 21 urban communities in
South Africa and Zambia in 2013 before a community randomized trial of
combination prevention-HPTN 071 (PopART). It draws on participatory research
conducted in each community, which carried out group discussions and interviews
with 1202 respondents and 203 structured observations. Participants were largely
unfamiliar with the concepts of UTT and TasP. They were concerned about an
accompanying de-emphasis on sexual behavior change. Treatment and prevention
seemed, at first glance, to be experienced separately. With the exception of the
prevention of mother-to-child transmission, prevention seldom came into
discussions about ART. This was partly because this science had not yet been
explained to many and also because it was not an easy fit. Contemplating the link
between treatment and prevention, participants emphasized both PLHIV taking care
of themselves through good health and preventing disease progression and the
moral responsibility of PLHIV to prevent HIV transmission. To avoid igniting
moralizing and blaming when introducing UTT and TasP, we should capitalize on the
"taking care of yourself" legacy while boosting public responsibility through
broad antistigma education and patient empowerment efforts.
PMID- 27610466
TI - Expression of Inhibitor of Differentiation-1 and Its Effects on Angiogenesis in
Gastric Cancer.
AB - OBJECTIVE: To explore the effects of recombinant human endostatin (endostar, ES)
and cisplatin on the growth of gastric cancer-transplanted tumor in nude mice and
the expression of microvessel density (MVD). METHODS: Human gastric cancer SGC
7901 cells were subcutaneously injected into the armpit of nude mice to prepare
cancer-bearing nude mice. A total of 32 cancer-bearing nude mice were divided
into four groups (each group with 8 mice). The four groups included control group
and other three groups in which mice were treated with 5 mg/kg of ES (group E), 5
mg/kg of cisplatin (group Ci), and 5 mg/kg of ES combined with 5 mg/kg of
cisplatin (group C), respectively. MVD was determined by immunohistochemistry,
and the expressions of mRNA and protein of inhibitor of differentiation-1 (ID1)
and vascular endothelial growth factor (VEGF) were detected with reverse
transcription polymerase chain reaction (RT-PCR) and western blot, respectively.
Apoptosis was observed with transmission electron microscope. RESULTS: Compared
with control group, the sizes and weights of tumors were significantly decreased
in other three groups (all p < 0.05). MVD was significantly lower in groups E,
Ci, and C than in control group, and in groups E and C than in group Ci (all p <
0.05). Compared with control group, the expressions of mRNA and protein of ID1
and VEGF significantly decreased in groups E and C (all p < 0.05). There were no
significant differences in the expressions of mRNA and protein of ID1 and VEGF
between group Ci and control group. There was apoptosis in groups E and C, but no
apoptosis was found in group Ci and control group. CONCLUSION: ES can inhibit the
growth of gastric cancer cells through suppressing angiogenesis and promoting
apoptosis of tumor cell. This study provides a new idea for the treatment of
gastric cancer.
PMID- 27610467
TI - Interfering EZH2 Expression Reverses the Cisplatin Resistance in Human Ovarian
Cancer by Inhibiting Autophagy.
AB - We aimed to determine the effects of the inhibition of enhancer of zeste homolog
2 (EZH2) gene expression on the cisplatin resistance of the human ovarian cancer
cell line, SKOV3/DDP, and to identify the underlying mechanisms. SKOV3/DDP cells
were stably transfected with pSUPER-EZH2 (EZH2 RNA interference plasmid) or
pcDNA3.1-EZH2 (EZH2 gene overexpression plasmid) using the lipofection method.
Real-time fluorescence quantitative reverse transcription polymerase chain
reaction and western blotting confirmed that EZH2 expression was downregulated in
pSUPER-EZH2-transfected cells. Flow cytometry revealed that EZH2 inhibition did
not induce apoptosis, but significantly inhibited autophagy. In addition, it
significantly increased the expression of the cellular senescence-signaling
proteins p14(ARF), p16(INK4a), p53, pRb, and p21, and significantly decreased the
expression of cyclin-dependent kinase (CDK)1, CDK2, and H3K27me3. Cellular
senescence was characterized by a significant increase in the G0/G1 ratio and the
restoration of sensitivity to cisplatin in the drug-resistant cells. These
findings suggest that interfering with EZH2 expression can inhibit SKOV3/DDP cell
autophagy and reverse resistance to cisplatin. The underlying mechanisms could be
associated with the regulation of the cellular senescence-signaling pathway.
PMID- 27610468
TI - An Integrative Model of miRNA and mRNA Expression Signature for Patients of
Breast Invasive Carcinoma with Radiotherapy Prognosis.
AB - Radiotherapy is widely used in breast cancer treatment. The radiotherapy for
breast invasive carcinoma (BRCA) presents challenges with the complex clinical
factors, and too many genes have been found to be associated with BRCA
radiotherapy prognosis. The aim of this study was to construct an integrative
model to combine the clinical data and RNA expression data (including microRNA
and mRNA) to predict the survival durations of BRCA patients with radiotherapy.
Also, the authors try to find the key regulation pairs between mRNA and miRNA
from prediction. They collected mRNA and microRNA expression profiles and
gathered the corresponding clinical data of 73 BRCA patients with radiotherapy
from The Cancer Genome Atlas (TCGA). According to an integrative model from
univariate Cox regression between RNA expression and patient survival, they
classified the patients with radiotherapy into low-risk and high-risk groups. The
results showed that nine mRNAs were considered as protective genes and five
miRNAs and eight mRNAs were considered as high-risk genes. Moreover, the high
risk group has a significantly shorter survival time in comparison with the low
risk group by the log-rank test (p = 0.0039). The reliability of the gene
signature was validated by an independent data set from the Gene Expression
Omnibus (GEO). Furthermore, three pairs of miRNA-mRNA, closely associated to
survival, were identified. These findings and method may prove valuable for
improving the clinical management of BRCA patients with radiotherapy.
PMID- 27610469
TI - Abrogation of MUC5AC Expression Contributes to the Apoptosis and Cell Cycle
Arrest of Colon Cancer Cells.
AB - Deregulated expressions of mucins have been found in various malignancies and
play a pivotal role in carcinogenesis. MUC5AC, as a secreted mucin, is reported
to be aberrantly expressed during epithelial cancer progression, including colon
cancer. However, the mechanisms of the oncoprotein MUC5AC in the initiation of
colon cancer requires further investigation. Here, we collected colon cancer
tissues (n = 20) and corresponding paracancerous tissues (n = 20) and found that
the expression of MUC5AC was significantly elevated in colon cancer tissues when
compared with the corresponding paracancerous tissues. Immunofluorescence
indicated that all colon cancer cell lines, including HT29, SW620, and the normal
human intestinal epithelial cells FHC, showed the positive expression of MUC5AC,
and SW620 exhibited the highest expression. Moreover, knockdown of MUC5AC in
SW620 cells remarkably suppressed cell vitality and promoted apoptosis and G1
cell cycle arrest, resulting in the impaired ability of colony formation.
Furthermore, the inhibition of MUC5AC in SW620 cells dramatically repressed the
cell migration and invasion. These results demonstrated that MUC5AC as an
oncogene could be a promising target in the treatment of colon cancer.
PMID- 27610470
TI - High carrier concentration ZnO nanowire arrays for binder-free conductive support
of supercapacitors electrodes by Al doping.
AB - Doping semiconductor nanowires (NWs) for altering their electrical and optical
properties is a critical strategy for tailoring the performance of nanodevices.
Here, we prepared in situ Al-doped ZnO nanowire arrays by using continuous flow
injection (CFI) hydrothermal method to promote the conductivity. This reasonable
method offers highly stable precursor concentration for doping that effectively
avoid the appearance of the low conductivity ZnO nanosheets. Benefit from this,
three orders of magnitude rise of the carrier concentration from 1016cm-3 to
1019cm-3 can be achieved compared with the common hydrothermal (CH) mothed in
Mott-Schottky measurement. Possible effect of Al-doping was discussed by first
principle theory. On this basis, Al-doped ZnO nanowire arrays was developed as a
binder-free conductive support for supercapacitor electrodes and high capacitance
was triggered. It is owing to the dramatically decreased transfer resistance
induced by the growing free-moving electrons and holes. Our results have a
profound significance not merely in the controlled synthesis of other doping
nanomaterials by co-precipitation method but also in the application of binder
free energy materials or other materials.
PMID- 27610472
TI - Hybrid MWCNTs membrane with well-tunable wettability.
AB - With the development of surface science, surface with special wettability, such
as reversible or gradient, gradually becomes the focus of the field of science
now. Here, via a facile, green organic solvent-free route, we have fabricated
superhydrophobic hybrid MWCNTs membrane on mixed cellulose ester filter with
great flexibility and tailorability. Importantly, induced by acetic acid vapour
and NH3 vapour without external energy, wettability of it can be reversibly
switched between superhydrophobic (low adhesion) to hydrophobic (high adhesion).
Furthermore, hybrid MWCNTs membrane can achieve diverse range of gradient
wettability. The principle of theory behind phenomenon also has been explained
through surface chemical composition and microscopic surface topography by means
of Field-emission scanning electron microscope (FESEM) images, X-ray
photoelectron spectroscopy (XPS) and Fourier transformer infrared spectra (FTIR)
spectroscopy. This work has solved some critical problems in this field. The
limitations and potential application of our work also be summarized.
PMID- 27610471
TI - Performance of a novelly-defined zirconium metal-organic frameworks adsorption
membrane in fluoride removal.
AB - A novelly-defined adsorption membrane for rapid removal of fluoride from drinking
water was prepared. Both zirconium metal-organic frameworks (Zr-MOFs) adsorbent
and membrane with large specific surface area of 740.28m2/g were used for
fluoride removal for the first time. For adsorption technique, fluoride
adsorption on Zr-MOFs was studied on a batch mode. The adsorption data could be
well described by Langmuir isotherm model while the adsorption kinetic followed
pseudo-second-order model. The maximum of adsorption capacity was 102.40mg/g at
pH 7.0 when the initial fluoride concentration was 200mg/L. The FT-IR and XPS
analyses of Zr-MOFs revealed that both surface hydroxyl groups and Zr(IV) active
sites played important roles in fluoride adsorption process. The as-prepared Zr
MOFs adsorbent was suitable for practical treatment of drinking water and
regeneration by sodium hydroxide solution (3wt%). For membrane experiments, Zr
MOFs membrane supported on Alumina substrate could remove fluoride efficiently
through dynamic filtration. The fluoride removal capability of Zr-MOFs membrane
depended on flow rate and initial concentration of fluoride. The fluoride removal
abilities of Zr-MOFs membrane with 20MUm thickness could reach 5510, 5173, and
4664L/m2 when fluoride concentrations were 5, 8 and 10mg/L, respectively. This
study indicated that Zr-MOFs membrane could be developed into a very viable
technology for highly effective removal of fluoride from drinking water.
PMID- 27610473
TI - Facile synthesis of yeast cross-linked Fe3O4 nanoadsorbents for efficient removal
of aquatic environment contaminated with As(V).
AB - A facile solvothermal method was adopted to prepare monodispersed surface
functionalized Fe3O4 nanoparticles via self assembly process. The pure yeast,
diethylamine functionalized Fe3O4 nanoparticles (DMNPs) and yeast cross-linked
Fe3O4 nanoparticles (YcMNPs) were used for the efficient removal of arsenate from
aqueous solution. The crystal structure, morphology and magnetic properties of
these nanoparticles were characterized by using X-ray diffraction, field emission
scanning electron microscopy and vibrating sample magnetometer. The observed
physico-chemical properties confirms the metal binding nature of prepared
samples. The adsorption of As(V) on the functionalized magnetite nanoparticles
was tested under different operating conditions like contact time, adsorbate
dosage, adsorbate concentration and pH. The faster removal of As(V) was obtained
using YcMNPs (99%) than DMNPs and pure yeast. The adsorption equilibrium data
obeys Langmuir isotherm than Freundlich model and the kinetics data well depicts
the pseudo-second-order model. The batch column experiment confirms the adequate
desorption as well as reusability without significant loss of efficiency. The
results reveal the technical feasibility of the prepared nanoparticles for their
easy synthesis, recovery, cost effective, eco-friendly and a promising advanced
adsorbent for environmental pollution.
PMID- 27610474
TI - Hollow Porous VOx/C Nanoscrolls as High-Performance Anodes for Lithium-Ion
Batteries.
AB - Novel hollow porous VOx/C nanoscrolls are synthesized by an annealing process
with the VOx/octadecylamine (ODA) nanoscrolls as both vanadium and carbon
sources. In the preparation, the VOx/ODA nanoscrolls are first achieved by a two
phase solvothermal method using ammonium metavanadat as the precursor. Upon
subsequent heating, the intercalated amines between the vanadate layers in the
VOx/ODA nanoscrolls decompose into gases, which escape from inside the
nanoscrolls and leave sufficient pores in the walls. As the anodes of lithium-ion
batteries (LIBs), such hollow porous VOx/C nanoscrolls possess exceedingly high
capacity and rate capability (904 mAh g-1 at 1 A g-1) and long cyclic stability
(872 mAh g-1 after 210 cycles at 1 A g-1). The good performance is derived from
the unique structural features of the hollow hierarchical porous nanoscrolls with
low crystallinity, which could significantly suppress irreversible Li+ trapping
as well as improve Li+ diffusion kinetics. This universal method of annealing
amine-intercalated oxide could be widely applied to the fabrication of a variety
of porous electrode materials for high-performance LIBs and supercapacitors.
PMID- 27610475
TI - Contrast enhanced dual energy spectral mammogram, an emerging addendum in breast
imaging.
AB - OBJECTIVE: To assess the role of contrast-enhanced dual-energy spectral mammogram
(CEDM) as a problem-solving tool in equivocal cases. METHODS: 44 consenting
females with equivocal findings on full-field digital mammogram underwent CEDM.
All the images were interpreted by two radiologists independently. Confidence of
presence was plotted on a three-point Likert scale and probability of cancer was
assigned on Breast Imaging Reporting and Data System scoring. Histopathology was
taken as the gold standard. Statistical analyses of all variables were performed.
RESULTS: 44 breast lesions were included in the study, among which 77.3% lesions
were malignant or precancerous and 22.7% lesions were benign or inconclusive. 20%
of lesions were identified only on CEDM. True extent of the lesion was made out
in 15.9% of cases, multifocality was established in 9.1% of cases and ductal
extension was demonstrated in 6.8% of cases. Statistical significance for CEDM
was p-value <0.05. Interobserver kappa value was 0.837. CONCLUSION: CEDM has a
useful role in identifying occult lesions in dense breasts and in triaging
lesions. In a mammographically visible lesion, CEDM characterizes the lesion,
affirms the finding and better demonstrates response to treatment. Hence, we
conclude that CEDM is a useful complementary tool to standard mammogram. Advances
in knowledge: CEDM can detect and demonstrate lesions even in dense breasts with
the advantage of feasibility of stereotactic biopsy in the same setting. Hence,
it has the potential to be a screening modality with need for further studies and
validation.
PMID- 27610477
TI - Application of fuzzy neural networks for modeling of biodegradation and biogas
production in a full-scale internal circulation anaerobic reactor.
AB - This paper presents the development and evaluation of three fuzzy neural network
(FNN) models for a full-scale anaerobic digestion system treating paper-mill
wastewater. The aim was the investigation of feasibility of the approach-based
control system for the prediction of effluent quality and biogas production from
an internal circulation (IC) anaerobic reactor system. To improve FNN
performance, fuzzy subtractive clustering was used to identify model's
architecture and optimize fuzzy rule, and a total of 5 rules were extracted in
the IF-THEN format. Findings of this study clearly indicated that, compared to NN
models, FNN models had smaller RMSE and MAPE as well as bigger R for the testing
datasets than NN models. The proposed FNN model produced smaller deviations and
exhibited a superior predictive performance on forecasting of both effluent
quality and biogas (methane) production rates with satisfactory determination
coefficients greater than 0.90. From the results, it was concluded that FNN
modeling could be applied in IC anaerobic reactor for predicting the
biodegradation and biogas production using paper-mill wastewater.
PMID- 27610476
TI - Molecular basis for the mechanism of action of an anti-TACE antibody.
AB - Inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) have potential
as therapeutics for various diseases. Many small molecule inhibitors, however,
exhibit poor specificity profiles because they target the highly conserved
catalytic cleft of TACE. We report for the first time the molecular interaction
of a highly specific anti-TACE antagonistic antibody (MEDI3622). We characterized
the binding of MEDI3622 using mutagenesis, as well as structural modeling and
docking approaches. We show that MEDI3622 recognizes a unique surface loop of
sIVa-sIVb beta-hairpin on TACE M-domain, but does not interact with the conserved
catalytic cleft or its nearby regions. The exquisite specificity of MEDI3622 is
mediated by this distinct structural feature on the TACE M-domain. These findings
may aid the design of antibody therapies against TACE.
PMID- 27610478
TI - Gd@C82-(ethylenediamine)8 Nanoparticle: A New High-Efficiency Water-Soluble ROS
Scavenger.
AB - It is important to maintain a reactive oxygen species (ROS) balance in organisms;
thus, a valid ROS scavenger with good biocompatibility is urgently required. To
prepare a high-efficiency ROS scavenger, multiple ethylenediamine (EDA) groups
are bonded for the first time to a metallofullerene Gd@C82 to obtain water
soluble Gd@C82-(EDA)8 nanoparticles (NPs) through a facile solid-liquid reaction.
Gd@C82-(EDA)8 NPs with a relatively better conjugation possess an excellent
capability to scavenge hydroxyl radicals. Moreover, Gd@C82-(EDA)8 NPs exhibited a
remarkable cytoprotective effect against H2O2-induced injuries to human epidermal
keratinocytes-adult (HEK-a) cells at a low concentration of 2.5 MUM. In contrast,
Gd@C82-(OH)26 NPs that modified with hydroxyls show an apparent protective effect
at a much higher concentration of 40 MUM. This outstanding cytoprotective
performance of Gd@C82-(EDA)8 NPs is mainly attributed to their extremely high
cellular uptake and comparably strong conjugation. Gd@C82-(EDA)8 NPs with good
biocompatibility exhibit excellent ROS scavenging capability even at a
significantly low concentration, which promotes its versatile applications in
cosmetics and biomedicine.
PMID- 27610479
TI - Protonation State of MnFe and FeFe Cofactors in a Ligand-Binding Oxidase Revealed
by X-ray Absorption, Emission, and Vibrational Spectroscopy and QM/MM
Calculations.
AB - Enzymes with a dimetal-carboxylate cofactor catalyze reactions among the top
challenges in chemistry such as methane and dioxygen (O2) activation. Recently
described proteins bind a manganese-iron cofactor (MnFe) instead of the classical
diiron cofactor (FeFe). Determination of atomic-level differences of homo- versus
hetero-bimetallic cofactors is crucial to understand their diverse redox
reactions. We studied a ligand-binding oxidase from the bacterium Geobacillus
kaustophilus (R2lox) loaded with a FeFe or MnFe cofactor, which catalyzes O2
reduction and an unusual tyrosine-valine ether cross-link formation, as revealed
by X-ray crystallography. Advanced X-ray absorption, emission, and vibrational
spectroscopy methods and quantum chemical and molecular mechanics calculations
provided relative Mn/Fe contents, X-ray photoreduction kinetics, metal-ligand
bond lengths, metal-metal distances, metal oxidation states, spin configurations,
valence-level degeneracy, molecular orbital composition, nuclear quadrupole
splitting energies, and vibrational normal modes for both cofactors. A
protonation state with an axial water (H2O) ligand at Mn or Fe in binding site 1
and a metal-bridging hydroxo group (MUOH) in a hydrogen-bonded network is
assigned. Our comprehensive picture of the molecular, electronic, and dynamic
properties of the cofactors highlights reorientation of the unique axis along the
Mn-OH2 bond for the Mn1(III) Jahn-Teller ion but along the Fe-MUOH bond for the
octahedral Fe1(III). This likely corresponds to a more positive redox potential
of the Mn(III)Fe(III) cofactor and higher proton affinity of its MUOH group.
Refined model structures for the Mn(III)Fe(III) and Fe(III)Fe(III) cofactors are
presented. Implications of our findings for the site-specific metalation of R2lox
and performance of the O2 reduction and cross-link formation reactions are
discussed.
PMID- 27610480
TI - Clinical Characteristics and Treatment Outcomes of Recurrent Central Retinal Vein
Occlusions.
AB - PURPOSE: To report the ocular findings, systemic hematologic parameters, and
treatment outcomes of patients with recurrent central retinal vein occlusions
(CRVO). METHODS: A retrospective analysis of eyes that developed recurrent CRVO
was performed. Key exclusion criteria were follow-up of less than six months
after the recurrence, incomplete documentation, and recurrent macular edema in an
eye with a CRVO but without evidence of increased superficial hemorrhage or disc
edema (recurrent CRVO). Collected data included demographic information, history
of presenting illness including the previous CRVO, ocular and systemic co
morbidities, and clinical examination findings that included visual acuities and
imaging details from the time of initial CRVO diagnosis until the final
examination. RESULTS: Thirteen eyes of 12 subjects with recurrent CRVO were
evaluated. The mean age of the patients was 63 years (range: 42 to 79 years). The
mean interval between treatment of the initial CRVO and the onset of the
recurrent CRVO was 9.0 +/- 9.3 months. The visual acuity declined by
approximately eight lines at the time of recurrence. Treatment with vascular
endothelial growth factor inhibitors and corticosteroids significantly improved
mean central macular thickness (CMT) from the time of recurrence until the final
examination (808 +/- 169 vs. 511 +/- 302 um; P = 0.004), but failed to change
visual acuity (1.28 +/- 0.31 logMAR vs. 1.24 +/- 0.43 logMAR; P = 0.8). No
uncontrolled systemic risk factors were associated with recurrences. CONCLUSION:
Recurrent CRVO in the same eye occurs infrequently and may not be associated with
an uncontrolled systemic disease. Despite multimodal therapy, most eyes do not
recover vision to the pre-recurrence level.
PMID- 27610481
TI - Nanostructure Changes upon Polymerization of Aqueous and Organic Phases in
Organized Mixtures.
AB - The nanostructure of a microemulsion can be strongly affected by the liquid-to
solid transition during polymerization. Here, we examined the evolution of
nanostructures of different ternary mixtures, including two microemulsions and a
single lamellar phase that upon polymerization are quantitatively studied by
SAXS/WAXS and DSC experiments systematically performed before and after the
polymerization of both aqueous and organic phases. Samples are mixtures of the
poly(2-acrylamido-2-methylpropanesulfonic acid) network as the aqueous phase and
poly(hexyl methacrylate) as the organic phase stabilized by Brij35 surfactant.
Upon polymerization, the surfactant is excluded from the water/oil interface and
crystallizes, strongly changing the nanostructure of samples where it is the main
component. In samples where the aqueous phase is the main component, only a few
changes in structure are observed upon polymerization. This study demonstrates
quantitatively the possibility to preserve nanostructures during polymerization,
thus inducing a templating effect.
PMID- 27610482
TI - Assessing the experience of social support for parents who attended Camp
Trillium's pediatric oncology family program.
AB - : When a child is diagnosed with cancer, the entire family is affected by the
demands of the illness and its treatment. This study aimed to provide a more
nuanced understanding of the experience of parents of children with cancer when
participating in therapeutic recreation programs (such as summer camp) and to
address the specific knowledge gap of the role that camp may play in providing
social support for these families. In particular, this study aimed to enroll
mothers and fathers, as the voice of fathers has previously been missing in
research about cancer camps. METHOD: Qualitative methods were used to better
understand the experiences of parents (n = 85) attending Camp Trillium's family
program between June 26th and August 31st of 2012. Data obtained were analyzed
using a grounded theory approach and thus coded and then grouped using thematic
analysis. Parents reported that they experienced valuable peer interaction and
experienced an increase in their perceived social support. They also stated that
this support was sustained outside of the camp experience. Parents highlighted
the important aspects of camp as: the empowering setting, time to escape the
treatment routine, and rebuild familial relationships. From the qualitative
interviews, five distinct themes were explicated: (a) empowering setting, (b)
restoring family relationships, (c) valuable peer interactions, (d) information
sharing, and (e) group tensions. In addition to respite and recreational
opportunities, camp provides access to an environment and community that has the
ability to provide sustained and empowering support for parents dealing with
childhood cancer, notably for fathers.
PMID- 27610543
TI - Treatment of sentence comprehension and production in aphasia: is there cross
modal generalisation?
AB - Exploring generalisation following treatment of language deficits in aphasia can
provide insights into the functional relation of the cognitive processing systems
involved. In the present study, we first review treatment outcomes of
interventions targeting sentence processing deficits and, second report a
treatment study examining the occurrence of practice effects and generalisation
in sentence comprehension and production. In order to explore the potential
linkage between processing systems involved in comprehending and producing
sentences, we investigated whether improvements generalise within (i.e., uni
modal generalisation in comprehension or in production) and/or across modalities
(i.e., cross-modal generalisation from comprehension to production or vice
versa). Two individuals with aphasia displaying co-occurring deficits in sentence
comprehension and production were trained on complex, non-canonical sentences in
both modalities. Two evidence-based treatment protocols were applied in a
crossover intervention study with sequence of treatment phases being randomly
allocated. Both participants benefited significantly from treatment, leading to
uni-modal generalisation in both comprehension and production. However, cross
modal generalisation did not occur. The magnitude of uni-modal generalisation in
sentence production was related to participants' sentence comprehension
performance prior to treatment. These findings support the assumption of modality
specific sub-systems for sentence comprehension and production, being linked uni
directionally from comprehension to production.
PMID- 27610544
TI - Selective Derivatization of N-Terminal Cysteines Using Cyclopentenediones.
AB - The outcome of the Michael-type reaction between thiols and 2,2-disubstituted
cyclopentenediones varies depending on the thiol. Stable compounds with two fused
rings were formed upon reaction with 1,2-aminothiols (such as N-terminal
cysteines in peptides). Other thiols gave reversibly Michael-type adducts that
were in equilibrium with the starting materials. This differential reactivity
allows differently placed cysteines to be distinguished and has been exploited to
prepare bioconjugates incorporating two or three different moieties.
PMID- 27610545
TI - FOXE1 Polymorphism Interacts with Dietary Iodine Intake in Differentiated Thyroid
Cancer Risk in the Cuban Population.
AB - BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is low in Cuba,
and the contribution of dietary factors to DTC in this population has not been
investigated so far. The aim of this study was to evaluate the relationship
between dietary iodine intake and DTC with regard to the interaction with
environmental factors or some common single nucleotide polymorphisms (SNPs),
based on a case-control study carried out in Cuba. METHODS: A total of 203 cases
and 212 controls from the general population were interviewed face-to-face using
the dietary intake questionnaire and the photo booklet from the E3N cohort. A
specific food composition table was constructed for this study. For each
parameter studied, the odds ratio (OR) was stratified on age group and sex, and
further adjusted for dietary energy, smoking status, ethnic group, level of
education, number of pregnancies, and body surface area. RESULTS: The risk of DTC
was significantly reduced with increasing consumption of fish (p = 0.04), but no
association between total dietary iodine intake and DTC risk was evident (p =
0.7). This lack of significant association was true whatever the age, the smoking
status, the dietary selenium intake, and the ethnicity (p > 0.05). DTC risk was
positively and strongly associated with the number of copies in the minor allele
(A) for SNP rs965513 near FOXE1 among people who consumed less iodine than the
median (p = 0.005). CONCLUSION: Overall, the majority of the studied population
had an optimal dietary iodine intake. DTC risk was inversely associated with high
fish consumption. Furthermore, DTC risk was positively associated with the number
of copies in the minor allele (A) of rs965513 among people who consumed less
iodine than the median. Because these findings are based on post-diagnostic
measures, studies with pre-diagnostic dietary iodine are needed for confirmation.
PMID- 27610546
TI - Morphological Properties of Siloxane-Hydrogel Contact Lens Surfaces.
AB - PURPOSE: The aim of this study was to quantitatively characterize the
micromorphology of contact lens (CL) surfaces using atomic force microscopy (AFM)
and multifractal analysis. MATERIALS AND METHODS: AFM and multifractal analysis
were used to characterize the topography of new and worn siloxane-hydrogel CLs
made of Filcon V (I FDA group). CL surface roughness was studied by AFM in
intermittent-contact mode, in air, on square areas of 25 and 100 MUm2, by using a
Nanoscope V MultiMode (Bruker). Detailed surface characterization of the surface
topography was obtained using statistical parameters of 3-D (three-dimensional)
surface roughness, in accordance with ISO 25178-2: 2012. RESULTS: Before wear,
the surface was found to be characterized by out-of-plane and sharp structures,
whilst after a wear of 8 h, two typical morphologies were observed. One
morphology (sharp type) has a similar aspect as the unworn CLs and the other
morphology (smooth type) is characterized by troughs and bumpy structures. The
analysis of the AFM images revealed a multifractal geometry. The generalized
dimension Dq and the singularity spectrum f(alpha) provided quantitative values
that characterize the local scale properties of CL surface geometry at nanometer
scale. CONCLUSIONS: Surface statistical parameters deduced by multifractal
analysis can be used to assess the CL micromorphology and can be used by
manufacturers in developing CLs with improved surface characteristics. These
parameters can also be used in understanding the tribological interactions of the
back surface of the CL with the corneal surface and the front surface of the CL
with the under-surface of the eyelid (friction, wear, and micro
elastohydrodynamic lubrication at a nanometer scale).
PMID- 27610548
TI - Ultrasound in tarsal tunnel syndrome: Correct diagnosis for appropriate
treatment.
PMID- 27610549
TI - The Association Between Neck Pain and Pulmonary Function: A Systematic Review.
AB - The aim of this study was to systematically review the evidence on respiratory
function changes in patients with chronic neck pain. MEDLINE, Elsevier, ProQuest,
PubMed, Scopus, Springer, and Google scholar electronic databases were explored
thorough December 2015. English-language studies investigating cervical
musculoskeletal and respiratory parameters in patients with chronic neck pain
were included. Characteristics of the patients, sampling method and size,
musculoskeletal and respiratory parameters studied, and appropriateness of the
statistical tests were considered. Studies were rated based on study design and
performance. Of the 68 studies reviewed, 9 observational studies met our
inclusion criteria. Significant difference in maximum inspiratory and expiratory
pressures were reported in patients with chronic neck pain compared to
asymptomatic subjects. Some of the respiratory volumes were found to be lower in
patients with chronic neck pain. Muscle strength and endurance, cervical range of
motion, and psychological states were found to be significantly correlated with
respiratory parameters. Lower Pco2 in patients and significant relationship
between chest expansion and neck pain were also shown. Respiratory retraining was
found to be effective in improving some cervical musculoskeletal and respiratory
impairment. Functional pulmonary impairments accompany chronic neck pain. Based
on the observed association, investigation of the effectiveness of management of
CNP on respiratory function is strongly suggested.
PMID- 27610547
TI - Proliferation of Perivascular Macrophages Contributes to the Development of
Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques.
AB - The aim of the present study was to investigate if macrophage proliferation
occurs in the brain during simian immunodeficiency virus (SIV) infection of adult
macaques. We examined the expression of the Ki-67 proliferation marker in the
brains of uninfected and SIV-infected macaques with or without encephalitis.
Double-label immunohistochemistry using antibodies against the pan-macrophage
marker CD68 and Ki-67 showed that there was a significant increase in CD68+Ki-67+
cells in macaques with SIV encephalitis (SIVE) compared to uninfected and SIV
infected animals without encephalitis, a trend that was also confirmed in brain
samples from patients with HIV encephalitis. Multi-label immunofluorescence for
CD163 and Ki-67 confirmed that the vast majority of Ki-67+ nuclei were localized
to CD163+ macrophages in perivascular cuffs and lesions. The proliferative
capacity of Ki-67+ perivascular macrophages (PVM) was confirmed by their nuclear
incorporation of bromodeoxyuridine. Examining SIVE lesions, using double-label
immunofluorescence with antibodies against SIV-Gag-p28 and Ki-67, showed that the
population of Ki-67+ cells were productively infected and expanded proportionally
with lesions. Altogether, this study shows that there are subpopulations of
resident PVM that express Ki-67 and are SIV-infected, suggesting a mechanism of
macrophage accumulation in the brain via PVM proliferation.
PMID- 27610550
TI - Spinal Cord Injury During Ultrasound-Guided C7 Cervical Medial Branch Block.
AB - Ultrasound-guided cervical medial branch block (CMBB) is commonly performed to
diagnose and treat head, neck, and shoulder pain. However, its use at the C7
level has been shown to be less accurate than at other levels, which may increase
the chance of injury owing to the imprecision of needle site provided by the
ultrasound guide. We report the first case of iatrogenic spinal cord injury from
an ultrasound-guided C7 CMBB. The patient, upon receiving this procedure, had
fainted shortly after experiencing an electrical sensation that ran from the neck
to the toe. The patient complained of weakness and tingling sensation in the left
upper extremity. Cervical magnetic resonance imaging revealed a hematoma in the
cervical spinal cord, and an electrophysiological study, which was performed at 3
weeks after the incident, revealed an injury at the left C3-T2 anterior horn.
After 2 months of rehabilitation, the patient showed moderate improvement in the
strength of the left proximal upper extremity; however, there was no improvement
in the strength of the left distal upper extremity. Therefore, we recommend
caution when performing ultrasound-guided CMBB at the C7 level, as the guide
particularly at this level is relatively inaccurate, posing a risk of spinal cord
injury.
PMID- 27610552
TI - Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist:
Naproxen with Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo to Treating
Acute Low Back Pain: A Randomized Clinical Trial.
PMID- 27610551
TI - Reloading Promotes Recovery of Disuse Muscle Loss by Inhibiting TGFbeta Pathway
Activation in Rats After Hind Limb Suspension.
AB - OBJECTIVE: The purpose of this paper was to study the effect of transforming
growth factor beta (TGFbeta) signaling pathway on reloading-mediated restoration
of disuse muscle loss induced by hind limb suspension in rats. DESIGN: Rats were
divided into 4 groups: control group (CON), HLS group (hind limb suspension for 2
weeks), HLS + R group (hind limb suspension for 2 weeks followed by 2 weeks of
natural reloading), and HRS + E group (hind limb suspension for 2 weeks followed
by 2 weeks of treadmill exercise). Body weight, and weight and protein
concentration of gastrocnemius were determined. The expression of members of
canonical and noncanonical TGFbeta signaling pathways, including TGFbeta1,
myostatin (MSTN), phospho-smad2/3, phospho-mitogen-activated protein kinases
(p38, JNK1/2, and extracellular signal-regulated kinase 1 [ERK1]/ERK2), as well
as the corresponding downstream effectors of muscle mass-p21, Pax7, MyoD, and
MyoG-was determined at protein or messenger RNA (mRNA) levels. RESULTS: Reloading
increased MyoD mRNA and restored the decreased gastrocnemius weight/body weight
ratio, protein concentration of gastrocnemius, phospho-ERK2, Pax7 and the
increased TGFbeta1, MSTN, phospho-smad2/3, phospho-p38, phospho-JNK1/2, and p21
induced by hind limb suspension. Moreover, the effects of exercise reloading on
the restoration of gastrocnemius weight/body weight ratio, TGFbeta1, MSTN,
phospho-smad2, phospho-p38, phospho-JNK2, Pax7, as well as the induction of MyoD
mRNA were stronger than those of natural reloading. CONCLUSIONS: Disuse muscle
loss can be recovered by reloading in an intensity-dependent manner through
canonical and noncanonical TGFbeta signaling pathways. Pax7 and MyoD might be the
effectors of TGFbeta pathway in mediating the recovery effect of reloading.
PMID- 27610553
TI - Improving Exercise Performance with an Accelerometer-Based Smartphone App: A
Randomized Controlled Trial.
AB - OBJECTIVE: Proper exercise form is critical for the safety and efficacy of
therapeutic exercise. This research examines if a novel smartphone application,
designed to monitor and provide real-time corrections during resistance training,
can reduce performance errors and elicit a motor learning response. DESIGN: Forty
two participants aged 18 to 65 years were randomly assigned to treatment and
control groups. Both groups were tested for the number of movement errors made
during a 10-repetition set completed at baseline, immediately after, and 1 to 2
weeks after a single training session of knee extensions. The treatment group
trained with real-time, smartphone-generated feedback, whereas the control
subjects did not. Group performance (number of errors) was compared across test
sets using a 2-factor mixed-model analysis of variance. RESULTS: No differences
were observed between groups for age, sex, or resistance training experience.
There was a significant interaction between test set and group. The treatment
group demonstrated fewer errors on posttests 1 and 2 compared with pretest (P <
0.05). There was no reduction in the number of errors on any posttest for control
subjects. CONCLUSION: Smartphone apps, such as the one used in this study, may
enhance patient supervision, safety, and exercise efficacy across rehabilitation
settings. A single training session with the app promoted motor learning and
improved exercise performance.
PMID- 27610555
TI - It's a Hot World Out There.
PMID- 27610556
TI - The Strategic Revolution.
AB - On the 40(th) anniversary of the publication of Richard Dawkins's The Selfish
Gene, we explore the origins of cynical, strategic thinking in evolutionary
biology, investigate how this illuminated the sexual and social lives of animals,
and assess Dawkins's suggestion that evolution is best understood by taking the
gene's-eye view.
PMID- 27610554
TI - Comparative Analyses of Immunosuppressive Characteristics of Bone-Marrow,
Wharton's Jelly, and Adipose Tissue-Derived Human Mesenchymal Stem Cells.
AB - OBJECTIVE: Mesenchymal stem cells (MSCs), which possess immunosuppressive
characteristics on induced T-cells, were shown to be applicable in prevention and
treatment of graft-versus-host disease. However, knowledge of effective cell
sources is still limited. In this study, MSCs from different human tissues, i.e.
bone marrow (BM), Wharton's jelly (WJ), and adipose tissue, were isolated, and
the immune suppression of stimulated T cells was analyzed comparatively.
MATERIALS AND METHODS: MSCs were co-cultured with phytohemagglutinin-induced T
cells with co-culture techniques with and without cell-to-cell contact. After co
culture for 24 and 96 h, the proliferation rate of T cells was estimated by
carboxyfluorescein succinimidyl ester and apoptosis by annexin V/PI methods. Both
T cells and MSCs were analyzed with respect to gene expressions by real-time
polymerase chain reaction and their specific protein levels by ELISA. RESULTS:
The results showed that all three MSC lines significantly suppressed T-cell
proliferation; BM-MSCs were most effective. Similarly, T-cell apoptosis was
induced most strongly by BM-MSCs in indirect culture. In T cells, the genes in
NFkB and tumor necrosis factor pathways were silenced and the caspase pathway was
induced after co-culture. These results were confirmed with the measurement of
protein levels, like transforming growth factor beta1, IL-6, interferon-gamma,
interleukin (IL)-2, and tumor necrosis factor-alpha. Additionally, IL-17A was
detected in high levels in WJ-MSC co-cultures. We showed that IL-17A-producing
Tregs are the key mediators in the treatment of graft-versus-host disease.
CONCLUSION: BM-MSCs, which have been used in clinical applications for a while,
showed the greatest immunosuppressive effect compared to other MSCs. However, a
promising cell source could also be WJ, which is also effective in suppression
with fewer ethical concerns. We described the molecular mechanism of WJ-MSCs in
allogenic transplants for the first time.
PMID- 27610557
TI - Making the Most from Changes in Life.
PMID- 27610558
TI - iPS Cells 10 Years Later.
AB - In 2006, Takahashi and Yamanaka reported the breakthrough discovery of induction
of pluripotent stem cells from fibroblasts by a combination of defined factors.
Ten years later, Cell editor Joao Monteiro brings together Shinya Yamanaka and
Hans Scholer, one the original reviewers of the landmark study, to revisit the
history behind the paper and its long-lasting legacy.
PMID- 27610559
TI - Teaching a Clone to Walk, One Step at a Time.
AB - Development of broad HIV neutralizing antibodies during infection requires
prolonged exposure to viral variants. A series of three studies published in this
issue of Cell and a related paper in Immunity report new HIV structure-based
design efforts focused on sequential boosting regimens with antigens of
increasing maturation that point the way forward for an effective HIV vaccine
strategy.
PMID- 27610560
TI - Probing the Diversity of T Cell Dysfunction in Cancer.
AB - T cell dysfunction in cancer comes in many forms, with two new varieties reported
in this issue. Daley et al. find that T cells expressing gammadelta T cell
receptors (TCR) promote pancreatic tumor growth by inhibiting activation of T
cells with conventional TCRs. Singer et al. characterize dysfunctional tumor
infiltrating lymphocytes to reveal a role for zinc homeostasis in anti-tumor
immunity.
PMID- 27610561
TI - Gating Immunity and Death at the Nuclear Pore Complex.
AB - The nuclear pore complex is the primary conduit for nuclear import and export of
molecules. In this issue, Gu et al. uncover a novel mechanism in which immune
signaling and programmed cell death require nuclear pore rearrangement and
release of sequestered cyclin-dependent kinase inhibitors to elicit immunity and
death.
PMID- 27610562
TI - Cell-Type-Specific Optogenetics in Monkeys.
AB - The recent advent of technologies enabling cell-type-specific recording and
manipulation of neuronal activity spurred tremendous progress in neuroscience.
However, they have been largely limited to mice, which lack the richness in
behavior of primates. Stauffer et al. now present a generalizable method for
achieving cell-type specificity in monkeys.
PMID- 27610563
TI - Disease Tolerance Trick or Treat: Give Your Brain Something Good to Eat.
AB - The reprioritization of feeding motivations during disease is proposed to
optimize host defense strategies against infection. Now, Wang et al. identify
that sickness-induced anorexia differentially shapes the metabolic requirements
of cellular stress adaptations, leading to opposite impact on disease tolerance
upon bacterial versus viral infections.
PMID- 27610564
TI - Cellular Metabolism and Induced Pluripotency.
AB - The discovery of induced pluripotent stem cells (iPSCs) a decade ago, which we
are celebrating in this issue of Cell, represents a landmark discovery in
biomedical research. Together with somatic cell nuclear transfer, iPSC generation
reveals the remarkable plasticity associated with differentiated cells and
provides an unprecedented means for modeling diseases using patient samples. In
addition to transcriptional and epigenetic remodeling, cellular reprogramming to
pluripotency is also accompanied by a rewiring of metabolic pathways, which
ultimately leads to changes in cell identities.
PMID- 27610565
TI - In Vivo Cellular Reprogramming: The Next Generation.
AB - Cellular reprogramming technology has created new opportunities in understanding
human disease, drug discovery, and regenerative medicine. While a combinatorial
code was initially found to reprogram somatic cells to pluripotency, a "second
generation" of cellular reprogramming involves lineage-restricted transcription
factors and microRNAs that directly reprogram one somatic cell to another. This
technology was enabled by gene networks active during development, which induce
global shifts in the epigenetic landscape driving cell fate decisions. A major
utility of direct reprogramming is the potential of harnessing resident support
cells within damaged organs to regenerate lost tissue by converting them into the
desired cell type in situ. Here, we review the progress in direct cellular
reprogramming, with a focus on the paradigm of in vivo reprogramming for
regenerative medicine, while pointing to hurdles that must be overcome to
translate this technology into future therapeutics.
PMID- 27610566
TI - Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts.
AB - Whereas domestication of livestock, pets, and crops is well documented, it is
still unclear to what extent microbes associated with the production of food have
also undergone human selection and where the plethora of industrial strains
originates from. Here, we present the genomes and phenomes of 157 industrial
Saccharomyces cerevisiae yeasts. Our analyses reveal that today's industrial
yeasts can be divided into five sublineages that are genetically and
phenotypically separated from wild strains and originate from only a few
ancestors through complex patterns of domestication and local divergence. Large
scale phenotyping and genome analysis further show strong industry-specific
selection for stress tolerance, sugar utilization, and flavor production, while
the sexual cycle and other phenotypes related to survival in nature show decay,
particularly in beer yeasts. Together, these results shed light on the origins,
evolutionary history, and phenotypic diversity of industrial yeasts and provide a
resource for further selection of superior strains. PAPERCLIP.
PMID- 27610567
TI - Structure of a Complete Mediator-RNA Polymerase II Pre-Initiation Complex.
AB - A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre
initiation complex (Med-PIC) was assembled and analyzed by cryo-electron
microscopy and by chemical cross-linking and mass spectrometry. The resulting
complete Med-PIC structure reveals two components of functional significance,
absent from previous structures, a protein kinase complex and the Mediator
activator interaction region. It thereby shows how the kinase and its target, the
C-terminal domain of the polymerase, control Med-PIC interaction and
transcription.
PMID- 27610568
TI - Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric
Protein-Phospholipid Complex.
AB - Conjugative pili are widespread bacterial appendages that play important roles in
horizontal gene transfer, in spread of antibiotic resistance genes, and as sites
of phage attachment. Among conjugative pili, the F "sex" pilus encoded by the F
plasmid is the best functionally characterized, and it is also historically the
most important, as the discovery of F-plasmid-mediated conjugation ushered in the
era of molecular biology and genetics. Yet, its structure is unknown. Here, we
present atomic models of two F family pili, the F and pED208 pili, generated from
cryoelectron microscopy reconstructions at 5.0 and 3.6 A resolution,
respectively. These structures reveal that conjugative pili are assemblies of
stoichiometric protein-phospholipid units. We further demonstrate that each pilus
type binds preferentially to particular phospholipids. These structures provide
the molecular basis for F pilus assembly and also shed light on the remarkable
properties of conjugative pili in bacterial secretion and phage infection.
PMID- 27610569
TI - Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig
Knockin Mice.
AB - A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is
likely to be protective, but this has not been achieved. To explore immunization
regimens that might elicit bNAbs, we produced and immunized mice expressing the
predicted germline PGT121, a bNAb specific for the V3-loop and surrounding
glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed
to activate germline antibody-expressing B cells, followed by ELISA-guided
boosting with a sequence of directional immunogens, native-like trimers with
decreasing epitope modification, elicited heterologous tier-2-neutralizing
responses. In contrast, repeated immunization with the priming immunogen did not.
Antibody cloning confirmed elicitation of high levels of somatic mutation and
tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data
establish that sequential immunization with specifically designed immunogens can
induce high levels of somatic mutation and shepherd antibody maturation to
produce bNAbs from their inferred germline precursors.
PMID- 27610570
TI - Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing
Antibodies.
AB - Induction of broadly neutralizing antibodies (bnAbs) is a primary goal of HIV
vaccine development. VRC01-class bnAbs are important vaccine leads because their
precursor B cells targeted by an engineered priming immunogen are relatively
common among humans. This priming immunogen has demonstrated the ability to
initiate a bnAb response in animal models, but recall and maturation toward bnAb
development has not been shown. Here, we report the development of boosting
immunogens designed to guide the genetic and functional maturation of previously
primed VRC01-class precursors. Boosting a transgenic mouse model expressing
germline VRC01 heavy chains produced broad neutralization of near-native isolates
(N276A) and weak neutralization of fully native HIV. Functional and genetic
characteristics indicate that the boosted mAbs are consistent with partially
mature VRC01-class antibodies and place them on a maturation trajectory that
leads toward mature VRC01-class bnAbs. The results show how reductionist
sequential immunization can guide maturation of HIV bnAb responses.
PMID- 27610571
TI - Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor
Repertoires.
AB - The design of immunogens that elicit broadly reactive neutralizing antibodies
(bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to
assess potential immunogens is to use mice expressing precursors of human bnAbs
as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2
immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via
targeting the CD4 binding site of the envelope glycoprotein gp120. We now
describe a mouse vaccination model that allows a germline human IGHV1-2(*)02
segment to undergo normal V(D)J recombination and, thereby, leads to the
generation of peripheral B cells that express a highly diverse repertoire of
VRC01-related receptors. When sequentially immunized with modified gp120
glycoproteins designed to engage VRC01 germline and intermediate antibodies,
IGHV1-2(*)02-rearranging mice, which also express a VRC01-antibody precursor
light chain, can support the affinity maturation of VRC01 precursor antibodies
into HIV-neutralizing antibody lineages.
PMID- 27610572
TI - A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor
Infiltrating T Cells.
AB - Reversing the dysfunctional T cell state that arises in cancer and chronic viral
infections is the focus of therapeutic interventions; however, current therapies
are effective in only some patients and some tumor types. To gain a deeper
molecular understanding of the dysfunctional T cell state, we analyzed population
and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and
used genetic perturbations to identify a distinct gene module for T cell
dysfunction that can be uncoupled from T cell activation. This distinct
dysfunction module is downstream of intracellular metallothioneins that regulate
zinc metabolism and can be identified at single-cell resolution. We further
identify Gata-3, a zinc-finger transcription factor in the dysfunctional module,
as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that
it drives a dysfunctional phenotype in CD8(+) TILs. Our results open novel
avenues for targeting dysfunctional T cell states while leaving activation
programs intact.
PMID- 27610573
TI - Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral
Inflammation.
AB - Acute infections are associated with a set of stereotypic behavioral responses,
including anorexia, lethargy, and social withdrawal. Although these so-called
sickness behaviors are the most common and familiar symptoms of infections, their
roles in host defense are largely unknown. Here, we investigated the role of
anorexia in models of bacterial and viral infections. We found that anorexia was
protective while nutritional supplementation was detrimental in bacterial sepsis.
Furthermore, glucose was necessary and sufficient for these effects. In contrast,
nutritional supplementation protected against mortality from influenza infection
and viral sepsis, whereas blocking glucose utilization was lethal. In both
bacterial and viral models, these effects were largely independent of pathogen
load and magnitude of inflammation. Instead, we identify opposing metabolic
requirements tied to cellular stress adaptations critical for tolerance of
differential inflammatory states. VIDEO ABSTRACT.
PMID- 27610574
TI - Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.
AB - Defects in mitochondrial metabolism have been increasingly linked with age-onset
protein-misfolding diseases such as Alzheimer's, Parkinson's, and Huntington's.
In response to protein-folding stress, compartment-specific unfolded protein
responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to
ensure cellular protein homeostasis. While perturbation of individual
compartments can make other compartments more susceptible to protein stress, the
cellular conditions that trigger cross-communication between the individual UPRs
remain poorly understood. We have uncovered a conserved, robust mechanism linking
mitochondrial protein homeostasis and the cytosolic folding environment through
changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial
stress or small-molecule activators trigger changes in gene expression
coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the
cell from disease-associated proteins. Our data suggest an intricate and unique
system of communication between UPRs in response to metabolic changes that could
unveil new targets for diseases of protein misfolding.
PMID- 27610575
TI - Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis.
AB - During neurodegenerative disease, the toxic accumulation of aggregates and
misfolded proteins is often accompanied with widespread changes in peripheral
metabolism, even in cells in which the aggregating protein is not present. The
mechanism by which the central nervous system elicits a distal reaction to
proteotoxic stress remains unknown. We hypothesized that the endocrine
communication of neuronal stress plays a causative role in the changes in
mitochondrial homeostasis associated with proteotoxic disease states. We find
that an aggregation-prone protein expressed in the neurons of C. elegans binds to
mitochondria, eliciting a global induction of a mitochondrial-specific unfolded
protein response (UPR(mt)), affecting whole-animal physiology. Importantly, dense
core vesicle release and secretion of the neurotransmitter serotonin is required
for the signal's propagation. Collectively, these data suggest the commandeering
of a nutrient sensing network to allow for cell-to-cell communication between
mitochondria in response to protein folding stress in the nervous system.
PMID- 27610577
TI - PPM1A Functions as a Smad Phosphatase to Terminate TGFbeta Signaling.
PMID- 27610578
TI - Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape.
PMID- 27610576
TI - Dopamine Neuron-Specific Optogenetic Stimulation in Rhesus Macaques.
AB - Optogenetic studies in mice have revealed new relationships between well-defined
neurons and brain functions. However, there are currently no means to achieve the
same cell-type specificity in monkeys, which possess an expanded behavioral
repertoire and closer anatomical homology to humans. Here, we present a resource
for cell-type-specific channelrhodopsin expression in Rhesus monkeys and apply
this technique to modulate dopamine activity and monkey choice behavior. These
data show that two viral vectors label dopamine neurons with greater than 95%
specificity. Infected neurons were activated by light pulses, indicating
functional expression. The addition of optical stimulation to reward outcomes
promoted the learning of reward-predicting stimuli at the neuronal and behavioral
level. Together, these results demonstrate the feasibility of effective and
selective stimulation of dopamine neurons in non-human primates and a resource
that could be applied to other cell types in the monkey brain.
PMID- 27610579
TI - SnapShot: Biomolecular NMR.
AB - The essential principles of nuclear magnetic resonance for the analysis of
biomolecules are conveyed in this SnapShot.
PMID- 27610581
TI - Influence of Duration of Heroin Dependence on Humoral Immunologic Indicators.
AB - OBJECTIVE: The incidence of autoantibodies may be associated with the duration of
drug use. In this study, we assessed the association between the duration of
heroin dependence and various humoral immunologic indicators, including IgA, IgG,
IgM, complement component 3, complement component 4, rheumatoid factor, anti
beta2-glycoprotein 1 (IgA, IgG, IgM), antinuclear antibody, circulating immune
complexes, and cryoglobulins. METHODS: A total of 363 patients with heroin
dependence were enrolled in this cross-sectional and prospective study over a 3.5
year period. Depending on the duration of heroin use, participants were divided
into 3 groups: up to 3 years, 4 to 7 years, and more than 7 years of heroin
dependence. All patients were analyzed for the indicators. RESULTS: There was a
significant difference between the duration of heroin dependence and increased
concentration of IgA (P = 0.0000), IgG (P = 0.0000), IgM (P = 0.0001), complement
component 3 (P = 0.042), rheumatoid factor (P = 0.0001), anti-beta2-glycoprotein
1 (IgA, P = 0.0098; IgG, P = 0.0000; IgM, P = 0.0000), the presence of
antinuclear antibody (P = 0.01) and cryoglobulins (P = 0.0000), and decreased
concentration of complement component 4 (P = 0.002). There was no significant
difference in circulating immune complex concentration (P = 0.097). CONCLUSIONS:
A longer duration of heroin dependence was associated with increased
concentrations of IgA, IgG, IgM, complement component 3, rheumatoid factor, anti
beta2-glycoprotein 1 (IgA, IgG, IgM), presence of antinuclear antibodies and
cryoglobulins, and decreased concentrations of complement component 4, but there
was no influence on circulating immune complex values.
PMID- 27610580
TI - The Effect of Substance Use Disorders on the Association Between Guideline
concordant Long-term Opioid Therapy and All-cause Mortality.
AB - OBJECTIVE: Patients with substance use disorders (SUDs) prescribed long-term
opioid therapy (LtOT) are at risk for overdose and mortality. Prior research has
shown that receipt of LtOT in accordance with clinical practice guidelines has
the potential to mitigate these outcomes. Our objective was to determine whether
the presence of a SUD modifies the association between guideline-concordant care
and 1-year all-cause mortality among patients receiving LtOT for pain. METHODS:
Among HIV+ and HIV- patients initiating LtOT (>=90 days opioids) between 2000 and
2010 as part of the Veterans Aging Cohort Study, we used time-updated Cox
regression and propensity-score matching to examine-stratified by SUD status-the
association between 1-year all-cause mortality and 3 quality indicators derived
from national opioid-prescribing guidelines. Specifically, we examined whether
patients received psychotherapeutic cointerventions (>=2 outpatient mental health
visits), benzodiazepine coprescriptions (>=7 days), and SUD treatment (>=1
inpatient day or outpatient visit). These indicators were among those found in a
previous study to have a strong association with mortality. RESULTS: Among 17,044
patients initiating LtOT, there were 1048 (6.1%) deaths during 1 year of follow
up. Receipt of psychotherapeutic cointerventions was associated with lower
mortality in the overall sample and was more protective in patients with SUDs
(adjusted hazard ratio [AHR] 0.43, 95% confidence interval [CI] 0.33-0.56 vs AHR
0.65, 95% CI 0.53-0.81; P for interaction = 0.002). Benzodiazepine coprescribing
was associated with higher mortality in the overall sample (AHR 1.41, 95% CI 1.22
1.63), but we found no interaction by SUD status (P for interaction = 0.11).
Among patients with SUDs, receipt of SUD treatment was associated with lower
mortality (AHR 0.43, 95% CI 0.33-0.57). CONCLUSIONS: For clinicians prescribing
LtOT to patients with untreated SUDs, engaging patients with psychotherapeutic
and SUD treatment services may reduce mortality. Clinicians should also avoid,
when possible, prescribing opioids with benzodiazepines.
PMID- 27610583
TI - Mammography Patient Information at Hospital Websites: Most Neither Comprehensible
Nor Guideline Supported.
AB - OBJECTIVE: Ongoing controversy regarding screening mammography guidelines has
created confusion for many patients. Given recommendations that patient
educational material be prepared at or below the 7th grade reading level of
average Americans, the purpose of this study was to assess the readability of
online mammography information offered by hospitals nationwide. MATERIALS AND
METHODS: During 2015, online mammography patient educational materials were
identified for all Medicare-recognized hospitals nationwide for which screening
mammography metrics were publicly available. Patient educational materials were
assessed using six validated readability score algorithms. All references to
official screening guidelines were captured. RESULTS: Of 4105 hospitals
nationwide, 3252 had websites and confirmable screening mammography services. Of
those, 1753 (54%) offered mammography information material online. Only 919 (28%)
referenced any professional society guidelines. After excluding information not
formatted in HTML and shorter than 100 words (to improve algorithm reliability),
1524 hospital mammography webpages were assessed for grade level scores.
Nationally, the mean of each readability score for all hospitals varied between
the 10th and 14th grade levels, all higher than the recommended 7th grade level
(p < 0.001). At the individual hospital level, only 14 hospitals (0.4%) had mean
scores at or below the 7th grade level. CONCLUSION: Of U.S. hospitals that offer
screening mammography and have websites, only 54% provide online mammography
educational material. Of those, only 0.4% present information at a reading level
comprehensible to average Americans, and only 28% offer specific information to
help patients reconcile conflicting guidelines. Health systems offering
mammography should strive to better meet women's health information and literacy
needs.
PMID- 27610582
TI - Alcohol, Cannabis, and Opioid Use Disorders, and Disease Burden in an Integrated
Health Care System.
AB - OBJECTIVES: We examined prevalence of major medical conditions and extent of
disease burden among patients with and without substance use disorders (SUDs) in
an integrated health care system serving 3.8 million members. METHODS: Medical
conditions and SUDs were extracted from electronic health records in 2010.
Patients with SUDs (n = 45,461; alcohol, amphetamine, barbiturate, cocaine,
hallucinogen, and opioid) and demographically matched patients without SUDs (n =
45,461) were compared on the prevalence of 19 major medical conditions. Disease
burden was measured as a function of 10-year mortality risk using the Charlson
Comorbidity Index. P-values were adjusted using Hochberg's correction for
multiple-inference testing within each medical condition category. RESULTS: The
most frequently diagnosed SUDs in 2010 were alcohol (57.6%), cannabis (14.9%),
and opioid (12.9%). Patients with these SUDs had higher prevalence of major
medical conditions than non-SUD patients (alcohol use disorders, 85.3% vs 55.3%;
cannabis use disorders, 41.9% vs 23.0%; and opioid use disorders, 44.9% vs 26.1%;
all P < 0.001). Patients with these SUDs also had higher disease burden than non
SUD patients; patients with opioid use disorders (M = 0.48; SE = 1.46) had
particularly high disease burden (M = 0.23; SE = 0.09; P < 0.001). CONCLUSIONS:
Common SUDs, particularly opioid use disorders, are associated with substantial
disease burden for privately insured individuals without significant impediments
to care. This signals the need to explore the full impact SUDs have on the course
and outcome of prevalent conditions and initiate enhanced service engagement
strategies to improve disease burden.
PMID- 27610584
TI - Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults
receiving extracorporeal membrane oxygenation.
AB - PURPOSE: The objective of this study was to evaluate the use of sedative,
analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing
extracorporeal membrane oxygenation (ECMO) support. MATERIALS AND METHODS: This
was a 2-year, prospective, observational study of adult intensive care unit
patients on ECMO support for more than 48hours. RESULTS: We analyzed 32 patients,
including 15 receiving VA (venoarterial) ECMO and 17 VV (venovenous) ECMO. The
median daily dose of benzodiazepines (midazolam equivalents) was 24mg, and the
median daily dose of opioids (fentanyl equivalents) was 3875 MUg. There was a
moderate negative correlation between the day of ECMO and the median daily
benzodiazepine dose (r=-0.5515) and a very weak negative correlation for the
median daily opioid dose (r=-0.0053). On average, patients were sedated to
Richmond Agitation Sedation Scale scores between 0 and -1. Continuous infusions
of opioids, benzodiazepines, propofol, dexmedetomidine, and NMBAs were
administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%)
ECMO days, respectively. Patients in the VA arm received a continuous infusion
opioid (96.4% vs 81.6% days; P<.001) and benzodiazepine (58.2% vs 37.0% days;
P<.001) more frequently. CONCLUSIONS: Patients received relatively low doses of
sedatives and analgesics while at a light level of sedation on average. Patients
rarely required neuromuscular blockade.
PMID- 27610585
TI - Ischemia-modified albumin is a predictor of short-term mortality in patients with
severe sepsis.
AB - PURPOSE: One of the most important events leading to morbidity and mortality in
patients with severe sepsis is the development of global tissue hypoperfusion and
oxidative damage. Ischemia-modified albumin (IMA), an albumin generated under
ischemic and oxidative conditions, is a marker of oxidative stress and
hypoperfusion. Here, we investigated whether IMA level could predict short-term
mortality with severe sepsis. METHODS: A prospective cohort study was conducted
from April 2014 to October 2014 in intensive care units in a tertiary hospital.
At the onset of severe sepsis, serum IMA level was measured, and baseline and
laboratory data, infection sources, and underlying diseases were recorded;
Sequential Organ Failure Assessment and Acute Physiology and Chronic Health
Evaluation II scores were calculated. Multivariate logistic regression and
receiver operating characteristic curve analyses were used to evaluate predictors
of mortality. Kaplan-Meier analysis was used to compare survival at day 28.
RESULTS: A total of 117 patients with severe sepsis were included (overall 28-day
mortality, 24.8%). The IMA level was higher in nonsurvivors than in survivors (P
< .05). It was a strong predictor of 28-day mortality (area under the receiver
operating characteristic curve, 0.742; P < .001), and the optimal cutoff for IMA
level maximizing sensitivity and specificity was 110 U/mL. On multivariate
logistic regression, Acute Physiology and Chronic Health Evaluation II score and
IMA level were independent risk factors for death. Survival rate was reduced with
very high IMA level (>=110 U/mL; P < .05). CONCLUSIONS: The IMA level, especially
at least 110 U/mL, may be a useful predictor of death for patients with severe
sepsis.
PMID- 27610586
TI - Decreased a disintegrin-like and metalloprotease with thrombospondin type 1 motif
13 activity and neurologic outcome in patients with successful resuscitation of
out-of-hospital cardiac arrest: A prospective observational study.
AB - PURPOSE: The purpose of this study is to investigate the association between a
disintegrin-like and metalloprotease with thrombospondin type 1 motif 13
(ADAMTS13) and neurologic outcome in patients with resuscitation of out-of
hospital cardiac arrest (R-OHCA). MATERIALS AND METHODS: A prospective
observational study of adult patients with R-OHCA was conducted. Plasma activity
of ADAMTS13 and inflammatory markers, an immunologic marker, and a marker of
endothelial damage were measured on admission and day 2. Neurologic outcome was
evaluated using the Cerebral Performance Categories on day 90. RESULTS: Plasma
activity of ADAMTS13 on day 2 was lower in patients with poor neurologic outcome
(n = 18) than that in those with good neurologic outcome (n = 16; P = .008). It
was also lower in 28-day nonsurvivors (n = 12) than in survivors (n = 21; P =
.019). Soluble thrombomodulin showed a strong correlation with ADAMTS13 (P =
.021). Furthermore, ADAMTS13 activity was negatively correlated with the
Sequential Organ Failure Assessment score (P < .001), levels of high-mobility
group box 1 (P = .028), and levels of interleukin 6 (P = .047) but positively
correlated with the monocyte expression of human leukocyte antigen DR (P = .023).
CONCLUSION: Decreased ADAMTS13 activity was associated with poor neurologic
outcome, high mortality, and worsened immune-inflammatory status in patients with
R-OHCA. These results suggest that ADAMTS13 may have pathophysiologic relevance
in postcardiac arrest syndrome.
PMID- 27610587
TI - Guillain-Barre syndrome in patients with a recent history of Zika in Cucuta,
Colombia: A descriptive case series of 19 patients from December 2015 to March
2016.
AB - PURPOSE: Zika virus (ZIKV) infection is an emerging global threat and a public
health problem in the Americas. Guillain-Barre syndrome (GBS) has been recently
associated to ZIKV. This report presents a case series of GBS possibly associated
to ZIKV. METHODS: Clinical and demographic data from patients with GBS treated in
5 intensive care units and with recent history of ZIKV in Cucuta, Colombia were
collected from December 1 2015 to April 30 2016. Electrophysiological
examination, lumbar puncture, and reverse transcriptase-polymerase chain reaction
for ZIKV were performed in 14, 10, and 1 patients, respectively. RESULTS:
Nineteen patients with GBS and a recent history of acute viral syndrome
compatible with ZIKV infection were studied (mean age, 44 years; range, 17-78).
Neurologic symptoms developed at a median of 10 days after the onset of the viral
symptoms. Albuminocytological dissociation was found in 8 cases.
Electrophysiological criteria for acute motor axonal neuropathy were found in all
patients tested. Five patients met level 1, 8 patients level 2, and 6 patients
level 3 of diagnostic certainty for GBS in the Brighton classification. Fifteen
patients required respiratory assistance, 16 received intravenous
immunoglobulins, and 3 had plasmapheresis. Seventy-nine percent of patients were
in Hughes GBS disability scale 4 to 5 at discharge and no patients died during
the observation period. Acute ZIKV infection, confirmed by reverse transcriptase
polymerase chain reaction, was observed for 1 patient. CONCLUSIONS: All cases of
this GBS outbreak had a recent history ZIKV infection, reinforcing existing
evidence for the association between GBS and ZIKV. Future genetic and immunologic
studies are warranted to further investigate the cause of the outbreak in detail.
PMID- 27610588
TI - Clinical significance of palliative care assessment in patients referred for
urgent intensive care unit admission: A cohort study.
AB - PURPOSE: To evaluate clinical characteristics of patients with palliative care
(PC) and urgent intensive care unit (ICU) referrals in the same hospital
admission. METHODS: All urgent ICU referrals at an academic, tertiary hospital,
and the co-occurrence and timing of PC assessment were retrieved from a
prospectively collected database. RESULTS: From May 2014 to May 2015, 2476
patients were analyzed and 179 (7%) had co-occurrence of PC assessment and urgent
ICU referral in the same hospital admission. Hospital mortality was higher (odds
ratio, 8.3; 95% confidence interval, 5.4-12.7) and ICU admission was lower (odds
ratio, 0.54; 95% confidence interval, 0.40-0.74) in patients with PC assessment,
compared with patients without concurrent PC and ICU referrals. Variables
associated with PC assessment were older age, diagnosis of cancer, depressed
level of consciousness, nonsurgical admission, lower performance status,
physician's subjective prognosis of poor outcome, and length of hospitalization
before ICU referral. CONCLUSION: In this cohort of patients with urgent ICU
referral, clinical characteristics at the moment of ICU referral were associated
with co-occurrence of PC assessment in the same hospital admission. These
characteristics might guide the development of instruments to enhance early
referral of high-risk patients to PC services.
PMID- 27610589
TI - Mass production of two-dimensional oxides by rapid heating of hydrous chlorides.
AB - Two-dimensional (2D) nanoscale oxides have attracted research interest owing to
their electronic, magnetic optical and catalytic properties. If they could be
manufactured on a large scale, 2D oxides would be attractive for applications
ranging from electronics to energy conversion and storage. Herein, we report
facile fabrication of oxide nanosheets by rapid thermal annealing of
corresponding hydrous-chloride compounds. By heating CrCl3.6H2O, ZrOCl2.8H2O,
AlCl3.6H2O and YCl3.6H2O crystals as precursors, we immediately collect large
quantities of ultrathin Cr2O3, ZrO2, Al2O3 and Y2O3 nanosheets, respectively. The
formation of layered nanosheets relies on exfoliation driven by rapid evaporation
of water and/or other gas molecules generated under annealing. Our route allows
simple, efficient and inexpensive production of 2D oxides. As a demonstration, we
evaluate Cr2O3 nanosheets prepared by our method as anodes in lithium-ion
batteries and find superior performance in comparison with their microcrystalline
counterparts.
PMID- 27610590
TI - Effects of depressive symptoms and coping motives on naturalistic trends in
negative and positive alcohol-related consequences.
AB - OBJECTIVE: Depressive symptoms and drinking to cope with negative affect increase
the likelihood for drinking-related negative consequences among college students.
However, less is known about their influence on the naturalistic trajectories of
alcohol-related consequences. In the current study, we examined how positive and
negative drinking-related consequences changed as a function of depressive
symptoms and drinking motives (coping, conformity, social, enhancement). METHOD:
Participants (N=652; 58% female) were college student drinkers assessed biweekly
during the first two years of college. We used hierarchical linear modeling to
examine means of and linear change in positive and negative consequences related
to depression and motives, controlling for level of drinking. RESULTS: Consistent
with hypotheses, negative and positive consequences decreased over the course of
freshman and sophomore years. Higher levels of depression were associated with a
faster decline in negative consequences during freshman year. Coping motives
predicted average levels of negative and positive consequences across all years,
with the effects of coping motives on consequences most pronounced at low levels
of depression during sophomore year. CONCLUSIONS: These findings indicate that
screening students for depression and drinking to cope, independent of alcohol
consumption, may help identify students at risk for experiencing negative alcohol
consequences and that these factors should be addressed in targeted alcohol
interventions.
PMID- 27610591
TI - An ounce of prevention: A pre-randomization protocol to improve retention in
substance use disorder clinical trials.
AB - BACKGROUND: Missing data in substance use disorder (SUD) research pose a
significant threat to internal validity. Participants terminate involvement or
become less likely to attend intervention and research visits for many reasons,
which should be addressed prior to becoming problematic. During a 9-month study
targeting stimulant abuse, early dropouts and participant reported attendance
barriers led to implementing a structured, pre-randomization protocol with
participants about retention and solution-focused strategies (the "Fireside
Chat"). Our aim is to outline this approach and present data on intervention
participation and research visit attendance after implementation. METHODS/DESIGN:
STimulant Reduction using Dosed Exercise (STRIDE) was a two-arm, multisite
randomized clinical trial testing treatment-as-usual for stimulant
abuse/dependence augmented by Exercise or Health Education. For both groups,
study intervention visits at the site were scheduled 3/week for 12weeks followed
by 1/week for 24weeks. During The Chat, research staff thoroughly reviewed
participants' expectations, and barriers and solutions to retention. Fifteen
participants were randomized (to Exercise or Health Education) prior to and
fourteen were randomized after Chat implementation. Intervention and monthly
follow-up attendance (before and after implementation) were compared at the site
(N=29) that developed and rigorously implemented The Chat. RESULTS: Individuals
who participated in The Chat (n=14) attended significantly more intervention
visits during weeks 1-12 (p<0.001) and weeks 13-36 (p<0.05) and attended more
research visits (p<0.001). DISCUSSION: Proactive discussion of expectations and
barriers prior to randomization was associated with greater study attendance. SUD
researchers should consider tailoring this approach to suit their needs. Further
investigation is warranted.
PMID- 27610594
TI - Using Feily's method prevented scalp necrosis in three patients incline to the
scalp recipient necrosis; what is new in prevention of scalp necrosis?
AB - Serious complications arising from surgical hair restoration are relatively
uncommon following well-performed and well-planned surgery by skillful surgical
techniques, good communication, and postoperative follow-up. Surgical
complications often categorized as those which occur in the donor site and the
recipient site. In this paper among recipient area complication we focused on
recipient area necrosis that arises when an increased number of recipient grafts
are utilized and de-vascularization of the scalp occurs as a result of the large
wound area due to the dense packing splitting of recipient skin. Recently, Feily
et al. explained an interesting method to prevent development of recipient area
necrosis following a hair transplant procedure. Herein we reported three cases of
dense hair transplantation using the Feilys method that after slitting they
troubled by unusual long lasting dark areas on the scalp and they need more than
24 hr's patience for prevention of scalp necrosis.
PMID- 27610592
TI - Correlation between antibodies to bisphenol A, its target enzyme protein
disulfide isomerase and antibodies to neuron-specific antigens.
AB - Evidence continues to increase linking autoimmunity and other complex diseases to
the chemicals commonly found in our environment. Bisphenol A (BPA) is a synthetic
monomer used widely in many forms, from food containers to toys, medical products
and many others. The potential for BPA to participate as a triggering agent for
autoimmune diseases is likely due to its known immunological influences. The goal
of this research was to determine if immune reactivity to BPA has any correlation
with neurological antibodies. BPA binds to a target enzyme called protein
disulfide isomerase (PDI). Myelin basic protein (MBP) and myelin oligodendrocyte
glycoprotein (MOG) are neuronal antigens that are target sites for
neuroinflammation and neuroautoimmunity. We determined the co-occurrence of anti
MBP and anti-MOG antibodies with antibodies made against BPA bound to human serum
albumin in 100 healthy human subjects. Correlation between BPA to PDI, BPA to
MOG, BPA to MBP, PDI to MBP and PDI to MOG were all highly statistically
significant (P < 0.0001). The outcome of our study suggests that immune
reactivity to BPA-human serum albumin and PDI has a high degree of statistical
significance with substantial correlation with both MBP and MOG antibody levels.
This suggests that BPA may be a trigger for the production of antibodies against
PDI, MBP and MOG. Immune reactivity to BPA bound to human tissue proteins may be
a contributing factor to neurological autoimmune disorders. Further research is
needed to determine the exact relationship of these antibodies with
neuroautoimmunities. Copyright (c) 2016 The Authors Journal of Applied Toxicology
Published by John Wiley & Sons Ltd.
PMID- 27610593
TI - Estrogen receptors alpha and beta and aromatase as independent predictors for
prostate cancer outcome.
AB - Androgens are considered important in normal prostate physiology and prostate
cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa
recurrence is still lacking. This indicates additional mediators contributing to
cancer development. We sought to determine the prognostic significance of
estrogen receptors, ERalpha and -beta, and the aromatase enzyme in PCa. Tissue
microarrays were created from 535 PCa patients treated with radical
prostatectomy. Expression of ERalpha, ERbeta and aromatase were evaluated using
immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS)
areas were investigated separately. Survival analyses were used to evaluate the
markers correlation to PCa outcome. In univariate analyses, ERalpha in TS was
associated with delayed time to clinical failure (CF) (p = 0.042) and PCa death
(p = 0.019), while ERbeta was associated with reduced time to biochemical failure
(BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF
and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these
observations, indicating an independent prognostic impact of all markers. When
stratifying the analysis according to different surgical centers the results were
unchanged. In conclusion, significant prognostic roles of ERalpha, ERbeta and
aromatase were discovered in the in PCa specimens of our large multicenter
cohort.
PMID- 27610595
TI - Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma:
comparison of sGalectin-1, sCD163 and sCD30 with TARC.
AB - Soluble Galectin-1 (sGal-1, also termed LGALS1), soluble CD163 (sCD163) and
soluble CD30 (sCD30) have been reported to be elevated in plasma or serum of
patients with classical Hodgkin lymphoma (cHL). We aimed to determine the
clinical utility of these biomarkers for evaluation of treatment response
compared to thymus and activation regulated chemokine (TARC, also termed CCL17).
Plasma or serum samples were prospectively collected among 103 newly diagnosed
cHL patients before and after treatment. Levels of sGal-1, sCD163, sCD30 and TARC
were correlated with disease characteristics and clinical treatment response.
Elevated plasma levels of sGal-1, sCD163, sCD30 and TARC were found in 67%, 21%,
91% and 93% of cHL patients respectively. Mean plasma levels of sGal-1 and sCD30
decreased after treatment but sCD163 did not decrease after treatment. There was
no correlation with change of these markers and clinical treatment response in
individual patients. TARC levels strongly correlated with disease characteristics
and metabolic volume. TARC remained high in 6 out of 7 non-responsive patients
and dramatically decreased in 95 out of 96 responsive patients. In summary,
elevated pre-treatment levels of sGal-1, sCD163, sCD30 and TARC can be found in
patients with cHL. However, only plasma TARC accurately reflects disease activity
and correlates with clinical treatment response.
PMID- 27610596
TI - Application of dual 19 F and iron cellular MRI agents to track the infiltration
of immune cells to the site of a rejected stem cell transplant.
AB - PURPOSE: Cellular MRI) was used to detect implanted human mesenchymal stem cells
(hMSCs) and the resulting macrophage infiltration that occurs in response to
xenotransplantation. METHODS: Human mesenchymal stem cells were prelabeled with a
fluorine-19 (19 F) agent prior to implantation, allowing for their visualization
and quantification over time. Following implantation of 1 * 10619 F-labeled hMSCs
into the mouse hind limb, longitudinal imaging was performed to monitor the stem
cell graft. Macrophages were labeled in situ by the intravenous administration of
an ultrasmall superparamagentic iron oxide (USPIO), allowing for tracking of the
inflammatory response. RESULTS: Quantification of 19 F MRI on day 0 agreed with
the implanted number of cells, and 19 F signal decreased over time. By day 14,
only 22% +/- 11% of the original 19 F signal remained. In a second group, USPIO
were administered intravenously after implantation of 19 F-labeled hMSCs. When
imaged on day 2, a significant decrease in 19 F signal was observed compared to
the first group alongside a large signal void region in the corresponding proton
images. Immunohistochemistry confirmed the presence of iron-labeled macrophages
in the stem cell tract. CONCLUSION: A dual-labeling technique was used to
noninvasively track two distinct cell populations simultaneously. This
information could be used to provide additional insight into the cause of graft
failure. Magn Reson Med 78:713-720, 2017. (c) 2016 International Society for
Magnetic Resonance in Medicine.
PMID- 27610597
TI - The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.
AB - This article presents information on illicitly used synthetic cannabinoids.
Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of
abuse that act as full agonists of the cannabinoid type-1 receptor but have a
variety of additional pharmacologic effects. There are numerous cases of patient
harm and death in the United States, Europe, and Australia with many
psychological, neurological, cardiovascular, pulmonary, and renal adverse events.
Although most users prefer using cannabis, there are convenience, legal, and cost
reasons driving the utilization of synthetic cannabinoids. Clinicians should be
aware of pharmacologic and clinical similarities and differences between
synthetic cannabinoid and cannabis use, the limited ability to detect synthetic
cannabinoids in the urine or serum, and guidance to treat adverse events.
PMID- 27610599
TI - Report of the Association of Coloproctology of Great Britain and Ireland/British
Society of Gastroenterology Colorectal Polyp Working Group: the development of a
complex colorectal polyp minimum dataset.
AB - AIM: The management of large non-pedunculated colorectal polyps (LNPCPs) is
complex, with widespread variation in management and outcome, even amongst
experienced clinicians. Variations in the assessment and decision-making
processes are likely to be a major factor in this variability. The creation of a
standardized minimum dataset to aid decision-making may therefore result in
improved clinical management. METHOD: An official working group of 13
multidisciplinary specialists was appointed by the Association of Coloproctology
of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology
(BSG) to develop a minimum dataset on LNPCPs. The literature review used to
structure the ACPGBI/BSG guidelines for the management of LNPCPs was used by a
steering subcommittee to identify various parameters pertaining to the decision
making processes in the assessment and management of LNPCPs. A modified Delphi
consensus process was then used for voting on proposed parameters over multiple
voting rounds with at least 80% agreement defined as consensus. The minimum
dataset was used in a pilot process to ensure rigidity and usability. RESULTS: A
23-parameter minimum dataset with parameters relating to patient and lesion
factors, including six parameters relating to image retrieval, was formulated
over four rounds of voting with two pilot processes to test rigidity and
usability. CONCLUSION: This paper describes the development of the first reported
evidence-based and expert consensus minimum dataset for the management of LNPCPs.
It is anticipated that this dataset will allow comprehensive and standardized
lesion assessment to improve decision-making in the assessment and management of
LNPCPs.
PMID- 27610598
TI - Factors Associated with Transition from Community Settings to Hospital as Place
of Death for Adults Aged 75 and Older: A Population-Based Mortality Follow-Back
Survey.
AB - OBJECTIVES: To identify factors associated with end-of-life (EoL) transition from
usual place of care to the hospital as place of death for people aged 75 and
older. DESIGN: Population-based mortality follow-back survey. SETTING: Deaths
over 6 months in 2012 in two unitary authorities in England covering 800 square
miles with more than 1 million residents. PARTICIPANTS: A random sample of people
aged 75 and older who died in a care home or hospital and all those who died at
home or in a hospice unit (N = 882). Cases were identified from death
registrations. The person who registered the death (a relative for 98.9%)
completed the survey. MEASUREMENTS: The main outcome was EoL transition to the
hospital as place of death versus no EoL transition to the hospital.
Multivariable modified Poisson regression was used to examine factors (illness,
demographic, environmental) related to EoL transition to the hospital. RESULTS:
Four hundred forty-three (50.2%) individuals responded, describing the care of
the people who died. Most died from nonmalignant conditions (76.3%) at a mean age
of 87.4 +/- 6.4. One hundred forty-six (32.3%) transitioned to the hospital and
died there. Transition was more likely for individuals with respiratory disease
than for those with cancer (prevalence ratio (PR) = 2.07, 95% confidence interval
(CI) = 1.42-3.01) and for people with severe breathlessness (PR = 1.96, 95% CI =
1.12-3.43). Transition was less likely if EoL preferences had been discussed with
a healthcare professional (PR = 0.60, 95% CI = 0.42-0.88) and when there was a
key healthcare professional (PR = 0.74, 95% CI = 0.58-0.95). CONCLUSION: To
reduce EoL transition to the hospital for older people, there needs to be
improved management of breathlessness in the community and better access to a key
healthcare professional skilled in coordinating care, communication, facilitating
complex discussions, and in planning for future care.
PMID- 27610600
TI - Oral literacy demand in the pediatric dental clinic: a pilot study.
AB - BACKGROUND: The parent's ability to obtain, process, and understand important
oral health information (i.e., their oral health literacy) is directly related to
their child's oral health status. AIM: To assess the relationship between oral
literacy demands placed on parents by dentists and parents' understanding of
dental information given to them. DESIGN: Thirty-one consenting primary
caregivers of children attending their first dental visit completed a demographic
survey, a REALD-30 test, and a survey to test understanding of dental
information. Dental appointments, performed by eight pediatric dental residents,
were audio-recorded and transcribed for qualitative analysis and descriptive
statistics. RESULTS: Factors associated with language complexity were
significantly higher in dental residents (R) than participants (P), that is,
total number of words spoken (R: 1615.09 + 859.91 vs P: 480.68 + 232.034) and
words per sentence (R: 8.82 + 1.74 vs P: 4.91 + 1.71). Speaking turns did not
differ between resident and parent (R: 94.64 vs P: 83.27). CONCLUSIONS: Although
the dialogue between the participating dentists and parents was highly unequal,
parents understood about 86% of the information provided by the resident. Future
studies are needed to identify factors associated with gaps in the educational
process of parents in the dental setting.
PMID- 27610601
TI - Neurological Outcome in Fetuses with Mild and Moderate Ventriculomegaly.
AB - Introduction Ventriculomegaly (VM) is one the most frequent anomalies detected on
prenatal ultrasound. Magnetic resonance imaging (MRI) may enhance diagnostic
accuracy and prediction of developmental outcome in newborns. Purpose The aim of
this study was to assess the correlation between ultrasound and MRI in fetuses
with isolated mild and moderate VM. The secondary aim was to report the
neurodevelopmental outcome at 4 years of age. Methods Fetuses with a prenatal
ultrasound (brain scan) diagnosis of VM were identified over a 4-year period.
Ventriculomegaly was defined as an atrial width of 10-15 mm that was further
divided as mild (10.1-12.0 mm) and moderate (12.1-15.0 mm). Fetuses with VM
underwent antenatal as well as postnatal follow-ups by brain scan and MRI.
Neurodevelopmental outcome was performed using the Griffiths Mental Development
Scales and conducted, where indicated, until 4 years into the postnatal period.
Results Sixty-two fetuses were identified. Ventriculomegaly was bilateral in 58%
of cases. A stable dilatation was seen in 45% of cases, progression was seen in
13%, and regression of VM was seen in 4.5% respectively. Fetal MRI was performed
in 54 fetuses and was concordant with brain scan findings in 85% of cases.
Abnormal neurodevelopmental outcomes were seen in 9.6% of cases. Conclusion
Fetuses in whom a progression of VM is seen are at a higher risk of developing an
abnormal neurodevelopmental outcome. Although brain scan and MRI are
substantially in agreement in defining the grade of ventricular dilatation, a low
correlation was seen in the evaluation of VM associated with central nervous
system (CNS) or non-CNS abnormalities.
PMID- 27610602
TI - MicroRNA inhibition fine-tunes and provides robustness to the restriction point
switch of the cell cycle.
AB - The restriction point marks a switch in G1 from growth factor-dependent to growth
factor-independent progression of the cell cycle. The proper regulation of this
switch is important for normal cell processes; aberrations could result in a
number of diseases such as cancer, neurodegenerative disorders, stroke and
myocardial infarction. To further understand the regulation of the restriction
point, we extended a mathematical model of the Rb-E2F pathway to include members
of the microRNA cluster miR-17-92. Our mathematical analysis shows that microRNAs
play an essential role in fine-tuning and providing robustness to the switch. We
also demonstrate how microRNA regulation can steer cells in or out of cancer
states.
PMID- 27610603
TI - Copper-Catalyzed Oxidation of Alkanes with H2 O2 under a Fenton-like Regime.
AB - Copper complexes bearing readily available ligand systems catalyzed the oxidation
of alkanes with H2 O2 as the oxidant with high efficiency in remarkable yields
(50-60 %). The reactions proceeded with unprecedented selectivity to give alkyl
hydroperoxides as the major products. Detailed scrutiny of the reaction mechanism
suggests the involvement of C-centered and O-centered radicals generated in a
Fenton-like fashion.
PMID- 27610604
TI - Prevalent new-user cohort designs for comparative drug effect studies by time
conditional propensity scores.
AB - PURPOSE: Studies of the real-world comparative effectiveness of drugs conducted
using computerized healthcare databases typically involve an incident new-user
cohort design for head-to-head comparisons between two medications, using
exclusively treatment-naive patients. However, the desired contrast often
involves one new drug compared with an older drug, of which many users of the new
drug may have switched from, seriously restricting the scope of incident new-user
studies. METHODS: We introduce prevalent new-user cohort designs for head-to-head
comparative drug effect studies, where incident new users are scarce. We define
time-based and prescription-based exposure sets to compute time-conditional
propensity scores of initiating the newer drug and to identify matched subjects
receiving the comparator drug. We illustrate this approach using data from the
UK's Clinical Practice Research Datalink to evaluate whether the newer glucagon
like peptide-1 receptor agonists (GLP-1 analogs) used to treat type 2 diabetes
increase the risk of heart failure, in comparison with the older similarly
indicated sulfonylureas. RESULTS: Of the 170 031 users of antidiabetic agents
from 2000 onwards, 79 682 used sulfonylureas (first use 2000), while 6196 used
GLP-1 analogs (first use 2007), 75% of which had previously used a sulfonylurea.
After matching each GLP-1 analog user to a sulfonylurea user on the time
conditional propensity scores from prescription-based exposure sets, the hazard
ratio of heart failure with GLP-1 use was 0.73 (95%CI: 0.57-0.93). CONCLUSION:
The proposed prevalent new-user cohort design for comparative drug effects
studies allows the use of all or most patients exposed to the newer drug, thus
permitting a more comprehensive assessment of a new drug's safety. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27610606
TI - Erratum.
PMID- 27610605
TI - Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic
microinjection of CRISPR/Cas9 into zygotes.
AB - BACKGROUND: Xenotransplantation is considered to be a promising solution to the
growing demand for suitable donor organs for transplantation. Despite tremendous
progress in the generation of pigs with multiple genetic modifications thought to
be necessary to overcoming the severe rejection responses after pig-to-non-human
primate xenotransplantation, the production of knockout pigs by somatic cell
nuclear transfer (SCNT) is still an inefficient process. Producing genetically
modified pigs by intracytoplasmic microinjection of porcine zygotes is an
alluring alternative. The porcine GGTA1 gene encodes for the alpha1,3
galactosyltransferase that synthesizes the Gal epitopes on porcine cells which
constitute the major antigen in a xenotransplantation setting. GGTA1-KO pigs have
successfully been produced by transfecting somatic cells with zinc-finger
nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), or
CRISPR/Cas targeting GGTA1, followed by SCNT. METHODS: Here, we microinjected a
CRISPR/Cas9 vector coding for a single-guide RNA (sgRNA) targeting exon 8 of the
GGTA1 gene into the cytoplasm of 97 in vivo-derived porcine zygotes and
transferred 86 of the microinjected embryos into three hormonally synchronized
recipients. Fetuses and piglets were analyzed by flow cytometry for remaining Gal
epitopes. DNA was sequenced to detect mutations at the GGTA1 locus. RESULTS: Two
of the recipients remained pregnant as determined by ultrasound scanning on day
25 of gestation. One pregnancy was terminated on day 26, and six healthy fetuses
were recovered. The second pregnancy was allowed to go to term and resulted in
the birth of six healthy piglets. Flow cytometry analysis revealed the absence of
Gal epitopes in four of six fetuses (66%), indicating a biallelic KO of GGTA1.
Additionally, three of the six live-born piglets (50%) did not express Gal
epitopes on their cell surface. Two fetuses and two piglets showed a mosaicism
with a mixed population of Gal-free and Gal-expressing cells. Only a single
piglet did not have any genomic modifications. Genomic sequencing revealed indel
formation at the GGTA1 locus ranging from +17 bp to -20 bp. CONCLUSIONS: These
results demonstrate the efficacy of CRISPR/Cas to generate genetic modifications
in pigs by simplified technology, such as intracytoplasmic microinjection into
zygotes, which would significantly facilitate the production of genetically
modified pigs suitable for xenotransplantation. Importantly, this simplified
injection protocol avoids the penetration of the vulnerable pronuclear membrane,
and is thus compatible with higher survival rates of microinjected embryos, which
in turn facilitates production of genetically modified piglets.
PMID- 27610607
TI - Redox pathway sensing bile salts activates virulence gene expression in Vibrio
cholerae.
AB - Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, has
evolved signal transduction systems to control co-ordinately the expression of
virulence determinants. It was previously shown that the presence of the bile
salts glycocholate and taurocholate in the small intestine causes dimerization of
the transmembrane transcription factor TcpP by inducing intermolecular disulphide
bonds in the TcpP periplasmic domain. In this study, they further investigated
the mechanism of how taurocholate affects V. cholerae virulence determinants. In
vitro assay of TcpP oxidation by VcDsbA showed that VcDsbA induced TcpP
dimerization in the presence of taurocholate. Taurocholate bound to VcDsbA with a
KD of 40 +/- 2.5 MUM, and also bound other Dsb proteins, including EcDsbA, EcDsbC
and VcDsbC. Taurocholate inhibited VcDsbA reductase activity without affecting
VcDsbA secondary structure or thermostability. VcDsbA and its substrates were
more extensively reduced in the presence of taurocholate, as compared with their
redox state in the absence of taurocholate. The data presented here not only
provide new insights into the mechanism by which bile salts induce V. cholerae
virulence but also suggest a means by which to develop inhibitors against DsbA.
PMID- 27610608
TI - When personality is the problem: Managing patients with difficult personalities
on the acute care unit.
AB - Personality disorders are pervasive patterns of maladaptive behaviors, thoughts,
and emotions that often go unrecognized and can wreak havoc in the patient's
interpersonal life. These inflexible patterns of managing the world can be
disruptive when an individual is admitted to the hospital, causing distress for
both the patient who lacks the skills to deal with the expectations of the
hospital environment and the treatment team who can feel ill equipped to manage
such behavior. Having a personality disorder has implications for an individual's
healthcare outcomes; those with a personality disorder have a life expectancy
nearly 2 decades shorter than the general population for a multitude of reasons,
among them trouble interacting with the healthcare system. Although a diagnosis
of a specific personality disorder may be difficult to make on an acute care
unit, identification of dysfunctional personality structures can provide
opportunity for better management of an individual patient's medical and
psychological needs. This review focuses on the identification of these
individuals in the acute care setting and provides an overview of evidence-based
behavioral and pharmacological interventions. Journal of Hospital Medicine
2015;11:873-878. (c) 2015 Society of Hospital Medicine.
PMID- 27610609
TI - Amoxicillin-clavulanate for patients with acute exacerbation of chronic
rhinosinusitis: a prospective, double-blinded, placebo-controlled trial.
AB - BACKGROUND: The management of acute exacerbation of chronic rhinosinusitis
(AECRS) is still under debate, especially because there are no adequate studies
to support a best-evidence treatment for this condition. Antibiotic use for AECRS
has been recommended based on extrapolation of data from acute rhinosinusitis
(ARS) or non-placebo-controlled studies. This study aimed to evaluate whether
antibiotic therapy modifies the course of AECRS in a randomized, placebo
controlled study. METHODS: Patients with AECRS were randomized in a double
blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125
mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14
days. All patients were also treated with mometasone furoate and nasal washes
with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]),
quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic
score (Lund-Kennedy), and microbiological evaluation were compared to evaluate
the efficacy of antibiotic therapy in AECRS. RESULTS: Despite the majority of
bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%),
both AMX-CLAV and placebo-treated groups presented the same clinical course, with
no difference between groups. Both groups exhibited overall improvement of
symptoms on day 14 compared to day 0 (p < 0.01), especially the items "nasal
secretion" and "nasal obstruction" (p < 0.05). We also observed the same
evolution of nasal endoscopic and quality of life scores between placebo and AMX
CLAV. CONCLUSION: We concluded that AMX-CLAV for 14 days did not change the
clinical course of AECRS compared with placebo. The addition of an oral
antibiotic to ongoing topical intranasal steroid spray may not provide additional
benefit during management of AECRS.
PMID- 27610610
TI - Evaluation of Tp-e Interval, Tp-e/QT Ratio, and Tp-e/QTc Ratio in Patients with
Asymptomatic Arrhythmogenic Right Ventricular Cardiomyopathy.
AB - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by
progressive replacement of ventricular myocytes with variable amounts of fibrous
and adipose tissue. Several studies have suggested that the interval from the
peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the
transmural dispersion of repolarization and that increased Tp-e interval and Tp
e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this
study was to evaluate repolarization dispersion measured from the 12-lead surface
electrocardiogram (including Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio) in
asymptomatic ARVD patients METHODS: We selected 27 patients with asymptomatic
ARVD and 27 age- and gender-match young, healthy volunteers. RESULTS: Tp-e
interval, Tp-e/QT and Tp-e/QTc ratio were also significantly higher in ARVD group
compared to the control group (all P < 0.001). There were negative correlation
between S global and Tp-e, Tp-e/QT, Tp-e/QTc ration (r = -0.57, P = 0.02; r =
0.85, P = 0.02; r = -0.63, P < 0.01; respectively). There were also negative
correlation between Sm global and Tp-e, Tp-e/QT, Tp-e/QTc ration (r = -0.61, P <
0.01; r = -0.67, P < 0.01; r = -0.68, P < 0.01; respectively). Moreover, Em
global were negative correlation between Tp-e, Tp-e/QT, and Tp-e/QTc (r = - 0.64,
P < 0.001, r = - 0.75, P < 0.01; r = -0,69, P < 0.01; respectively) CONCLUSION:
In conclusion, we have presented strong evidence suggesting that Tp-e interval,
Tp-e/QT ratio, and Tp-e/QTc ratio were increased in asymptomatic ARVD patients.
PMID- 27610611
TI - The association between social participation and cognitive function in community
dwelling older populations: Japan Gerontological Evaluation Study at Taisetsu
community Hokkaido.
AB - OBJECTIVE: To study the association between the number of area-level and
individual-level social participation items and cognitive function in the
community-dwelling older populations of three towns in Hokkaido, Japan. METHODS:
A survey on the frequency of social participation was mailed to those in the
Japan Gerontological Evaluation Study 2013 who were aged >=65 years, were not
certified as needing long-term care, and lived in Higashikawa, Higashikagura, or
Biei. A subset of participants aged 70-74 years completed the Japanese version of
the Montreal Cognitive Assessment in a home visit survey. Both the area-level and
individual-level social participation and demographic information were obtained
on the self-administered questionnaire. A multilevel analysis using a generalized
linear mixed-effects model was used to examine the association between variables
in the area-level and individual-level social participation items and cognitive
function. RESULTS: Out of 4042 respondents, data from 2576 were used in the area
level analysis. Of those, 180 were aged 70-74 years and completed the home visit
survey for the individual-level analysis. A greater number of higher social
participation items at the individual level was associated with higher cognitive
function scores after adjusting for area-level social participation variables and
confounders (regression coefficient: 0.19; 95% confidence interval: 0.03, 0.35).
There were no significant associations between area-level social participation
item averages and individual-level cognitive function scores. CONCLUSIONS: Older
populations participating in many kinds of social activities exhibited preserved
cognitive function even after adjusting for area-level social participation
variables. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27610612
TI - Daniel Wartenberg: Empowering Community Epidemiology and Risk Analysis.
PMID- 27610613
TI - Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy:
Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque
Toxicology.
AB - The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have
shown remarkable antitumor activity in an increasing number of cancers. When
combined, ipilimumab and nivolumab have demonstrated superior activity in
patients with metastatic melanoma (CHECKMATE-067). Here we describe the
preclinical development strategy that predicted these clinical results.
Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was
observed with concurrent, but not sequential CTLA-4 and PD-1 blockade.
Significant antitumor activity was maintained using a fixed dose of anti-CTLA-4
antibody with decreasing doses of anti-PD-1 antibody in the MC38 model.
Immunohistochemical and flow cytometric analyses confirmed that CD3+ T cells
accumulated at the tumor margin and infiltrated the tumor mass in response to the
combination therapy, resulting in favorable effector and regulatory T-cell
ratios, increased pro-inflammatory cytokine secretion, and activation of tumor
specific T cells. Similarly, in vitro studies with combined ipilimumab and
nivolumab showed enhanced cytokine secretion in superantigen stimulation of human
peripheral blood lymphocytes and in mixed lymphocyte response assays. In a
cynomolgus macaque toxicology study, dose-dependent immune-related
gastrointestinal inflammation was observed with the combination therapy; this
response had not been observed in previous single agent cynomolgus studies.
Together, these in vitro assays and in vivo models comprise a preclinical
strategy for the identification and development of highly effective antitumor
combination immunotherapies.
PMID- 27610614
TI - Variation of Human Salivary O-Glycome.
AB - The study of saliva O-glycosylation is receiving increasing attention due to the
potential of glycans for disease biomarkers, but also due to easy access and non
invasive collection of saliva as biological fluid. Saliva is rich in
glycoproteins which are secreted from the bloodstream or produced by salivary
glands. Mucins, which are highly O-glycosylated proteins, are particularly
abundant in human saliva. Their glycosylation is associated with blood group and
secretor status, and represents a reservoir of potential disease biomarkers. This
study aims to analyse and compare O-glycans released from whole human mouth
saliva collected 3 times a day from a healthy individual over a 5 days period. O
linked glycans were released by hydrazinolysis, labelled with procainamide and
analysed by ultra-high performance liquid chromatography with fluorescence
detection (UHPLC-FLR) coupled to electrospray ionization mass spectrometry (ESI
MS/MS). The sample preparation method showed excellent reproducibility and can
therefore be used for biomarker discovery. Our data demonstrates that the O
glycosylation in human saliva changes significantly during the day. These changes
may be related to changes in the salivary concentrations of specific proteins.
PMID- 27610616
TI - Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of
a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery
EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730).
AB - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous
haematopoietic stem cells and enhances recovery in experimental stroke. Recovery
may also be dependent on an enriched environment and physical activity. G-CSF may
have the potential to enhance recovery when used in combination with
physiotherapy, in patients with disability late after stroke. METHODS: A pilot 2
x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind),
and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS
>1), at least 3 months after stroke. Primary outcome was feasibility,
acceptability and tolerability. Secondary outcomes included death, dependency,
motor function and quality of life measured 90 and 365 days after enrolment.
RESULTS: Recruitment to the trial was feasible and acceptable; of 118 screened
patients, 92 were eligible and 32 declined to participate. 60 patients were
recruited between November 2011 and July 2013. All participants received some
allocated treatment. Although 29 out of 30 participants received all 5 G
CSF/placebo injections, only 7 of 30 participants received all 18 therapy
sessions. G-CSF was well tolerated but associated with a tendency to more adverse
events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events
(SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned)
therapy sessions, interquartile range [12, 17]. Only a minority (23%) of
participants completed all physiotherapy sessions, a large proportion of sessions
(114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors
(20, 4%). No significant differences in functional outcomes were detected in
either the G-CSF or physiotherapy group at day 90 or 365. CONCLUSIONS: Delivery
of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate
feasibility for delivering additional physiotherapy sessions late after stroke
therefore a definitive study using this trial design is not supported. Future
work should occur earlier after stroke, alongside on-going clinical
rehabilitation. TRIAL REGISTRATION: ISRCTN.com ISRCTN16714730.
PMID- 27610617
TI - Decrease of Population Divergence in Eurasian Perch (Perca fluviatilis) in
Browning Waters: Role of Fatty Acids and Foraging Efficiency.
AB - Due to altered biogeochemical processes related to climate change, highly colored
dissolved organic carbon (DOC) from terrestrial sources will lead to a water
"brownification" in many freshwater systems of the Northern Hemisphere. This will
create deteriorated visual conditions that have been found to affect habitat
specific morphological variations in Eurasian perch (Perca fluviatilis) in a
previous study. So far, potential drivers and ultimate causes of these findings
have not been identified. We conducted a field study to investigate the
connection between morphological divergence and polyunsaturated fatty acid (PUFA)
composition of perch from six lakes across a gradient of DOC concentration. We
expected a decrease in the prevalence of PUFAs, which are important for perch
growth and divergence with increasing DOC concentrations, due to the
restructuring effects of DOC on aquatic food webs. In general, rate of
morphological divergence in perch decreased with increasing DOC concentrations.
Proportions of specific PUFAs (22:6n-3, 18:3n-3, 20:5n-3, and 20:4n-6) identified
to primarily contribute to overall differences between perch caught in clear and
brown-water lakes tended to be connected to overall decline of morphological
divergence. However, no overall significant relationship was found, indicating no
severe limitation of essential fatty acids for perch inhabiting brown water
lakes. We further broaden our approach by conducting a laboratory experiment on
foraging efficiency of perch. Therefore, we induced pelagic and littoral
phenotypes by differences in habitat-structure and feeding mode and recorded
attack rate in a feeding experiment. Generally, fish were less efficient in
foraging on littoral prey (Ephemeroptera) when visual conditions were degraded by
brown water color. We concluded that browning water may have a strong effect on
the forager's ability to find particular food resources, resulting in the reduced
development of evolutionary traits, such as habitat- specific morphological
divergence.
PMID- 27610615
TI - Oral Delivery of Pentameric Glucagon-Like Peptide-1 by Recombinant Lactobacillus
in Diabetic Rats.
AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by intestinal
cells and stimulates insulin secretion from the pancreas in a glucose-dependent
manner. Exogenously supplied GLP-1 analogues are used in the treatment of type 2
diabetes. An anti-diabetic effect of Lactobacillus in lowering plasma glucose
levels and its use as a vehicle for delivery of protein and antibody fragments
has been shown previously. The aim of this study was to employ lactobacilli as a
vehicle for in situ production and delivery of GLP-1 analogue to normalize blood
glucose level in diabetic GK (Goto-Kakizaki) rats. In this study, we designed
pentameric GLP-1 (5*GLP-1) analogues which were both expressed in a secreted form
and anchored to the surface of lactobacilli. Intestinal trypsin sites were
introduced within 5*GLP-1, leading to digestion of the pentamer into an active
monomeric form. The E. coli-produced 5*GLP-1 peptides delivered by intestinal
intubation to GK rats resulted in a significant improvement of glycemic control
demonstrated by an intraperitoneal glucose tolerance test. Meanwhile, the
purified 5*GLP-1 (trypsin-digested) from the Lactobacillus cultures stimulated
insulin secretion from HIT-T15 cells, similar to the E. coli-produced 5*GLP-1
peptides. When delivered by gavage to GK rats, non-expressor L. paracasei
significantly lowered the blood glucose level but 5*GLP-1 expression did not
provide an additional anti-diabetic effect, possibly due to the low levels
produced. Our results indicate that lactobacilli themselves might be used as an
alternative treatment method for type 2 diabetes, but further work is needed to
increase the expression level of GLP-1 by lactobacilli in order to obtain a
significant insulinotropic effect in vivo.
PMID- 27610618
TI - A Comparative Study on the Biological Characteristics of Human Adipose-Derived
Stem Cells from Lipectomy and Liposuction.
AB - PURPOSES: To compare the biological behaviors of human adipose-derived stem cells
(ADSCs) isolated from adipose tissue by lipectomy and liposuction, with the
purpose of providing the basis for clinical application. METHODS: The
proliferation and apoptosis of ADSCs were analyzed by CCK-8 assay and flow
cytometry. Cell migration was measured by a wound healing assay. An ELISA assay
was used to evaluate paracrine functions. SOD and MDA were tested by xanthine
oxidase and thiobarbituric acid reactions, respectively. In addition, we used a
CCK-8, LDH assay and flow cytometry to analyze the proliferation and apoptosis of
ADSCs treated with lidocaine or adrenaline. RESULTS: The viable ADSCs yield from
liposuction was significantly lower than that from lipectomy, while the apoptosis
of cells from liposuction was significantly higher than from lipectomy. The
paracrine secretion of the two sources of ADSCs was highest when treated with 10
7 mol/L insulin and 10 ng/mL TGF-alpha, but there were no significant differences
in VEGF, IL-6, IL-8 or HGF levels. The ADSCs from lipectomy migrated faster than
those from liposuction, and SOD in the lipectomy group was higher than in the
liposuction group, whereas MDA of the lipectomy group was lower than that of the
liposuction group. The proliferation ADSCs treated with lidocaine or adrenaline
was greatly decreased, while apoptosis was significantly increased, and
cytotoxicity of lidocaine or adrenaline to ADSCs was dose-dependent. CONCLUSIONS:
Compared with ADSCs from liposuction, the ADSCs from lipectomy have better
biological characteristics. Lidocaine and adrenaline decreased the viability of
ADSCs, and their cytotoxicity to ADSCs was dose-dependent.
PMID- 27610619
TI - Loss of Mll3 Catalytic Function Promotes Aberrant Myelopoiesis.
AB - Two of the most common myeloid malignancies, myelodysplastic syndrome (MDS) and
acute myeloid leukemia (AML), are associated with exceedingly low survival rates
despite recent therapeutic advances. While their etiology is not completely
understood, evidence suggests that certain chromosomal abnormalities contribute
to MDS and AML progression. Among the most frequent chromosomal abnormalities in
these disorders are alterations of chromosome 7: either complete loss of one copy
of chromosome 7 (-7) or partial deletion of 7q (del(7q)), both of which increase
the risk of progression from MDS to AML and are associated with chemoresistance.
Notably, 7q36.1, a critical minimally deleted region in 7q, includes the gene
encoding the histone methyltransferase mixed-lineage leukemia 3 (MLL3), which is
also mutated in a small percentage of AML patients. However, the mechanisms by
which MLL3 loss contributes to malignancy are unknown. Using an engineered mouse
model expressing a catalytically inactive form of Mll3, we found a significant
shift in hematopoiesis toward the granulocyte/macrophage lineage, correlating
with myeloid infiltration and enlargement of secondary lymphoid organs.
Therefore, we propose that MLL3 loss in patients may contribute to the
progression of MDS and AML by promoting myelopoiesis.
PMID- 27610620
TI - Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin
in Small Cell Lung Cancer Cells.
AB - Although small cell lung cancer (SCLC) is highly responsive to chemotherapies
(e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC
patients experience disease recurrence characterized by drug resistance. The
mechanisms underlying cisplatin resistance remain elusive. Here we report that
cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required
for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and
PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues,
and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared
to respective controls. Genetic abrogation of PD1 and PD-L1 in H69R and H82R
cells decreased their proliferation rate, and restored their sensitivity to
cisplatin. Mechanistically, PD-L1 upregulation in H69R and H82R cells was
attributed to the overexpression of DNA methyltransferase 1 (DNMT1) or receptor
tyrosine kinase KIT, as knockdown of DNMT1 or KIT in H69R and H82R cells led to
PD-L1 downregulation. Consequently, combined knockdown of PD-L1 with KIT or DNMT1
resulted in more pronounced inhibition of H69R and H82R cell growth. Thus, cell
intrinsic PD1/PD-L1 signaling may be a predictor for poor efficacy of cisplatin
treatment, and targeting the cellular PD1/PD-L1 axis may improve
chemosensitization of aggressive SCLC.
PMID- 27610621
TI - Protection of alpha-CaMKII from Dephosphorylation by GluN2B Subunit of NMDA
Receptor Is Abolished by Mutation of Glu96 or His282 of alpha-CaMKII.
AB - Interaction of CaMKII and the GluN2B subunit of NMDA receptor is essential for
synaptic plasticity events such as LTP. Synaptic targeting of CaMKII and
regulation of its biochemical functions result from this interaction. GluN2B
binding to the T-site of CaMKII leads to changes in substrate binding and
catalytic parameters and inhibition of its own dephosphorylation. We find that
CaMKIINalpha, a natural inhibitor that binds to the T-site of CaMKII, also causes
inhibition of dephosphorylation of CaMKII similar to GluN2B. Two residues on
alpha-CaMKII, Glu96 and His282, are involved in the inhibition of CaMKII
dephosphorylation exerted by binding of GluN2B. E96A-alpha-CaMKII is known to be
defective in GluN2B-induced catalytic modulation. Data presented here show that,
in both E96A and H282A mutants of alpha-CaMKII, GluN2B-induced inhibition of
dephosphorylation is impaired.
PMID- 27610622
TI - Regulation of Nociceptive Plasticity Threshold and DARPP-32 Phosphorylation in
Spinal Dorsal Horn Neurons by Convergent Dopamine and Glutamate Inputs.
AB - Dopamine can influence NMDA receptor function and regulate glutamate-triggered
long-term changes in synaptic strength in several regions of the CNS. In spinal
cord, regulation of the threshold of synaptic plasticity may determine the
proneness to undergo sensitization and hyperresponsiveness to noxious input. In
the current study, we increased endogenous dopamine levels in the dorsal horn by
using re-uptake inhibitor GBR 12935. During the so-induced hyperdopaminergic
transmission, conditioning low-frequency (1 Hz) stimulation (LFS) to the sciatic
nerve induced long-term potentiation (LTP) of C-fiber-evoked potentials in dorsal
horn neurons. The magnitude of LTP was attenuated by blockade of either dopamine
D1-like receptors (D1LRs) by with SCH 23390 or NMDA receptor subunit NR2B with
antagonist Ro25-6981. Conditioning LFS during GBR 12935 administration increased
phosphorylation of dopamine- and cAMP-regulated phosphoprotein of Mr 32kDa (DARPP
32) at threonine 34 residue in synaptosomal (P3) fraction of dorsal horn
homogenates, as assessed by Western blot analysis, which was partially prevented
by NR2B blockade prior to conditioning stimulation. Conditioning LFS also was
followed by higher co-localization of phosphorylated form of NR2B at tyrosine
1472 and pDARPP-32Thr34- with postsynaptic marker PSD-95 in transverse L5 dorsal
horn sections. Such increase could be significantly attenuated by D1LR blockade
with SCH 23390. The current results support that coincidental endogenous
recruitment of D1LRs and NR2B in dorsal horn synapses plays a role in regulating
afferent-induced nociceptive plasticity. Parallel increases in DARPP-32
phosphorylation upon LTP induction suggests a role for this phosphoprotein as
intracellular detector of convergent D1L- and NMDA receptor activation.
PMID- 27610623
TI - Identification of Genetic Associations and Functional Polymorphisms of SAA1 Gene
Affecting Milk Production Traits in Dairy Cattle.
AB - Our initial RNA sequencing (RNA-seq) revealed that the Serum amyloid A1 (SAA1)
gene was differentially expressed in the mammary glands of lactating Holstein
cows with extremely high versus low phenotypic values of milk protein and fat
percentage. To further validate the genetic effect and potential molecular
mechanisms of SAA1 gene involved in regulating milk production traits in dairy
cattle, we herein performed a study through genotype-phenotype associations. Six
identified SNPs were significantly associated with one or more milk production
traits (0.00002< P < 0.0025), providing additional evidence for the potential
role of SAA1 variants in milk production traits in dairy cows. Subsequently, both
luciferase assay and electrophoretic mobility shift assay (EMSA) clearly
demonstrated that the allele A of g.-963C>A increased the promoter activity by
binding the PARP factor while allele C did not. Bioinformatics analysis indicated
that the secondary structure of SAA protein changed by the substitution A/G in
the locus c. +2510A>G. Our findings were the first to reveal the significant
associations of the SAA1 gene with milk production traits, providing basis for
further biological function validation, and two identified SNPs, g.-963C>A and c.
+2510A>G, may be considered as genetic markers for breeding in dairy cattle.
PMID- 27610625
TI - Familiarity to a Feed Additive Modulates Its Effects on Brain Responses in Reward
and Memory Regions in the Pig Model.
AB - Brain responses to feed flavors with or without a feed additive (FA) were
investigated in piglets familiarized or not with this FA. Sixteen piglets were
allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI)
received a standard control feed and the familiarized group (FAM) received the
same feed added with a FA mainly made of orange extracts. Animals were subjected
to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16
and d 23. Production traits of the piglets were assessed up to d 28 post-weaning.
From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission
tomography of 18FDG) under anesthesia to investigate the brain activity triggered
by the exposure to the flavors of the feed with (FA) or without (C) the FA.
Images were analyzed with SPM8 and a region of interest (ROI)-based small volume
correction (p < 0.05, k >= 25 voxels per cluster). The brain ROI were selected
upon their role in sensory evaluation, cognition and reward, and included the
prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus
striatum. The FAM animals showed a moderate preference for the novel post
transition FA feed compared to the C feed on d 16, i.e., day of the feed
transition (67% of total feed intake). The presence or absence of the FA in the
diet from weaning had no impact on body weight, average daily gain, and feed
efficiency of the animals over the whole experimental period (p >= 0.10).
Familiar feed flavors activated the prefrontal cortex. The amygdala, insular
cortex, and prepyriform area were only activated in familiarized animals exposed
to the FA feed flavor. The perception of FA feed flavor in the familiarized
animals activated the dorsal striatum differently than the perception of the C
feed flavor in naive animals. Our data demonstrated that the perception of FA in
familiarized individuals induced different brain responses in regions involved in
reward anticipation and/or perception processes than the familiar control feed
flavor in naive animals. Chronic exposure to the FA might be necessary for
positive hedonic effects, but familiarity only cannot explain them.
PMID- 27610624
TI - Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition
Phenotypes.
AB - The human peripheral leukocyte subset composition depends on genotype variation
and pre-natal and post-natal environmental influence diversity. We quantified
this composition in adults and neonates, and compared the median values and
dispersal ranges of various subsets in them. We confirmed higher frequencies of
monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and
lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells
in neonatal umbilical cord blood. Unlike previous reports, we found higher
frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies
of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in
neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in
far greater detail than previously reported, using recently described surface
markers and gating strategies and observed that neonates had lower frequencies of
patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC)
ratios. Our data contribute to South Asian reference values for these parameters.
We found that dispersal ranges differ between different leukocyte subsets,
suggesting differential determination of variation. Further, some subsets were
more dispersed in adults than in neonates suggesting influences of postnatal
sources of variation, while some show the opposite pattern suggesting influences
of developmental process variation. Together, these data and analyses provide
interesting biological possibilities for future exploration.
PMID- 27610626
TI - Fertility Desires among Women Living with HIV.
AB - OBJECTIVE: Rates of pregnancy among women living with HIV (WLHIV) have increased
with the availability of effective HIV treatment. Planning for pregnancy and
childbirth is an increasingly important element of HIV care. Though rates of
unintended pregnancies are high among women in general, among couples affected by
HIV, significant planning and reproductive decisions must be considered to
prevent negative health consequences for WLHIV and their neonates. To gain
insight into this reproductive decision-making process among WLHIV, this study
explored women's knowledge, attitudes and practices regarding fertility planning,
reproductive desires, and safer conception practices. It was hypothesized that
pregnancy desires would be influenced by partners, families, the potential risk
of HIV transmission to infants, and physicians' recommendations. METHODS: WLHIV
of childbearing age were recruited from urban South Florida, and completed an
assessment of demographics (N = 49), fertility desires and a conjoint survey of
factors associated with reproductive decision-making. RESULTS: Using conjoint
analysis, we found that different decision paths exist for different types of
women: Younger women and those with less education desired children if their
partners wanted children; reproductive desires among those with less education,
and with less HIV pregnancy-related knowledge, displayed a trend toward
additional emphasis on their family's desires. Conversely, older women and those
with more education appeared to place more importance on physician endorsement in
their plans for childbearing. CONCLUSIONS: Results of this study highlight the
importance of ongoing preconception counselling for all women of reproductive age
during routine HIV care. Counselling should be tailored to patient
characteristics, and physicians should consider inclusion of families and/or
partners in the process.
PMID- 27610627
TI - Heart and Cardiovascular Involvement in Patients with Mucopolysaccharidosis Type
IVA (Morquio-A Syndrome).
AB - BACKGROUND: Mucopolysaccharidosis (MPS) IVA is a rare lysosomal storage disorder
with multiple skeletal and non-skeletal abnormalities requiring multiple surgical
interventions. It is well known that patients with MPS IVA suffer from
tachycardia, but cardiac and hemodynamic alterations have not been reported to
date. We investigated the cardiovascular and hemodynamic alterations in patients
with MPS IVA and developed a possible patho-mechanism for cardiovascular
deterioration during anesthesia. MATERIAL AND METHODS: In this observational
study, serial cardiac examinations were performed in 54 patients with MPS IVA who
were followed at the Children's Hospital of the Mainz Medical University (Mainz,
Germany) between 1991 and 2014 (follow-up 1-24 years; median 5.8 years). Results
were compared with data from a large central European cohort of more than 2000
healthy infants and children. RESULTS: None of the patients had arterial
hypertension, but 4% had evidence of increased pulmonary artery pressure.
Patients developed aortic root extension up to 6.9 standard deviations above
normal. Left-sided valve leaflet thickening occurred in 26 patients (five with
valve disease). Patients had lower left ventricular dimensions (z: -1.02+/-0.1),
lower stroke volumes (z: -2.3+/-0.17), lower left ventricular mass (z: -1.5+/
0.21), but higher wall thickness (z: +0.8+/-0.16), and higher work index (z:
+2.5+/-0.2) compared to healthy control subjects. Cardiac output was preserved by
an increase in heart rate of 21%. Sixty % of patients showed impaired diastolic
filling; heart rate (99.0+/-1.8 vs. 92.0+/-2.1 bpm), age (18.0+/-1.8 vs. 14.2+/-1
years), and cardiothoracic ratio (61.6+/-3.6% vs. 55+/-4.2%) of these patients
were higher compared to those with normal filling. CONCLUSIONS: The results of
this study suggest an age-progressive disproportion of the intra-thoracic organs
of patients with MPS IVA, which is accompanied by aortic root extension and
thickened left ventricles, with reduced stroke volumes, impaired diastolic
filling patterns, and increased heart rates.
PMID- 27610629
TI - Influence of Sterilization Technologies on Electrospun Poly(ester urea)s for Soft
Tissue Repair.
AB - Degradable poly(ester urea)s (PEU)s were electrospun into nanofiber sheets and
assessed for their potential to be used in soft tissue repair. The level of
residual solvent was measured and the effects of ethylene oxide and electron beam
sterilization techniques on molecular mass, mass distribution, and morphology
were quantified. Two PEU compositions that formed stable nanofiber sheets were
advanced into a pilot study in vitro and in vivo as candidate materials for
hernia repair. Cell viability, spreading, proliferation, and migration were
examined in vitro. Nanofiber sheets were implanted subcutaneously into mice and
analyzed via microangiography and histology for tissue incorporation. Nanofiber
sheets performed similarly to decellularized extracellular matrix (ECM) in vitro,
but the lack of sufficient pore structure inhibited cellular infiltration after
14 days of culture. The lack of microporous features in nanofiber sheets also
contributed to low levels of cellular infiltration, angiogenesis, and matrix
deposition in vivo. A preliminary study to increase pore size in nanofibers was
performed using coaxial electrospinning resulting in significant improvement in
tissue infiltration in vivo.
PMID- 27610628
TI - Cytomegalovirus Infection and Treatment in Allogeneic Hematopoietic Stem Cell
Transplantation: A Retrospective Study from a Single Institution in an Endemic
Area.
AB - OBJECTIVE: Although Cytomegalovirus (CMV) infection is a major complication after
allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors
for CMV reactivation and treatment failure in CMV endemic areas have remained
unclear. This study investigated the risk factors for CMV reactivation among allo
HSCT recipients in an area where CMV is highly endemic. MATERIALS AND METHODS:
Medical records of 82 allo-HSCT recipients from a CMV endemic area were
retrospectively reviewed. The patients were stratified into two groups: those
with CMV reactivation (n=32) and those without CMV reactivation (n=50). We
investigated possible variables associated with CMV reactivation and treatment
failure. RESULTS: Univariate analyses showed that non-remission disease status
[hazard ratio (HR): 2.15; p=0.032] and >=grade III acute graft-versus-host
disease (GVHD) (HR: 3.07; p=0.002) were associated with CMV reactivation.
Multivariate analysis further demonstrated that older age (HR: 1.03; p=0.029) and
>=grade III acute GVHD (HR: 2.98; p=0.012) were associated with CMV reactivation.
Overall survival time seemed lower among patients with CMV reactivation than
among patients without CMV reactivation, although the difference was not
statistically significant (p=0.165). The absence of >=grade III acute GVHD was
associated with successful CMV treatment in the current study (odds ratio: 4.40;
p=0.008). CONCLUSION: Prophylactic anti-CMV therapy might need to be considered
for allo-HSCT recipients who have >=grade III GVHD.
PMID- 27610631
TI - Geometry, Supertransfer, and Optimality in the Light Harvesting of Purple
Bacteria.
AB - The remarkable rotational symmetry of the photosynthetic antenna complexes of
purple bacteria has long been thought to enhance their light harvesting and
excitation energy transport. We study the role of symmetry by modeling
hypothetical antennas whose symmetry is broken by altering the orientations of
the bacteriochlorophyll pigments. We find that in both LH2 and LH1 complexes,
symmetry increases energy transfer rates by enabling the cooperative, coherent
process of supertransfer. The enhancement is particularly pronounced in the LH1
complex, whose natural geometry outperforms the average randomized geometry by
5.5 standard deviations, the most significant coherence-related enhancement found
in a photosynthetic complex.
PMID- 27610630
TI - Degradation of Ethylene Carbonate Electrolytes of Lithium Ion Batteries via Ring
Opening Activated by LiCoO2 Cathode Surfaces and Electrolyte Species.
AB - High-performance lithium-ion batteries require electrolytes that are stable over
wide operating voltages. We used density functional theory to investigate the
degradation of ethylene carbonate (EC) electrolytes activated by interactions
with LiCoO2 cathode surfaces and PF5 species in the electrolyte. We report
detailed mechanisms for the activation of EC ring-opening reactions by Lewis
acids to form CO2, organics, or organofluorines. We find that Lewis acid-base
complexation between EC and either PF5 or LiCoO2 weakens the C-O bonds of the EC
ring and consequently lowers the barrier to and energy of EC ring-opening
reactions. Our results predict that ring opening activated by the LiCoO2 cathode
surface forms a cathode-electrolyte interphase primarily composed of an organic
and organofluorine film. Simultaneous degradation of an EC molecule and PF6-
forms PF5 and a surface organofluorine with an activation barrier of 1.28 eV and
reaction energy of -0.26 eV. Ring opening of EC activated by the cathode to form
short organic oligomers results from sequential ring-opening reactions at the
surface with an activation barrier of 1.04 eV and an overall reaction enthalpy of
-1.15 eV for the case of EC dimer formation. Complexation of EC with PF5 lowers
the barrier to EC ring opening to form CO2 from 1.96 to 1.68 eV and the reaction
energy from 0.02 eV to -1.38 eV relative to unactivated CO2 formation. We expect
that EC electrolyte degradation at the cathode surface will be dominated by EC
dimer formation reactions activated by PF5 because of their low reaction barriers
relative to CO2 formation.
PMID- 27610632
TI - Electrochemical Detection of Trace Arsenic(III) by Nanocomposite of Nanorod-Like
alpha-MnO2 Decorated with ~5 nm Au Nanoparticles: Considering the Change of
Arsenic Speciation.
AB - It has been reported that the majority of groundwater shows weak alkaline in
which the As(III) species would be present as neutral H3AsO3 species and ionized
H2AsO3- species. However, as most reported previously, electrochemical detection
of As(III) has been operated under acidic conditions and the nonionic As(III)
(H3AsO3) is the dominant species. Therefore, considering the change of As(III)
speciation in different pH conditions, to develop a reliable method for the
detection of As(III) in alkaline media might be more meaningful for practical
applications. Here, combined the multilayer adsorption of nanorod-like alpha-MnO2
with the excellent electrocatalytic ability of ~5 nm Au nanoparticles (AuNPs), an
efficient and ultrahigh anti-interference electrochemical detection of As(III)
with AuNPs/alpha-MnO2 nanocomposite in alkaline media (nearly real water
environment) was developed. Notably, we have provided a thorough electrochemical
analytical investigation to confirm the advantage of As(III) detection in
alkaline media. The system was evaluated by a series of interference tests, and
no obvious interference from commonly coexisting substances (referring to the
groundwater, Togtoh region, Inner Mongolia, China) was observed in alkaline
media. Furthermore, electrodes robust stability and excellent reproducibility
were obtained. Under the optimized conditions, the limit of detection (3sigma
method) toward As(III) was 0.019 ppb, and the obtained sensitivity was 16.268 +/-
0.242 MUA ppb-1 cm-2. Finally, the proposed method has been successfully employed
for detection of As(III) in a real water sample.
PMID- 27610634
TI - A Disulfonimide Catalyst for Highly Enantioselective Mukaiyama-Mannich Reaction.
AB - A new BINOL-derived chiral disulfonimide has been developed by introducing 4
methyl-3,5-dinitrophenyl substituents at its 3- and 3'-positions. This chiral
disulfonimide catalyst displays high catalytic efficacy toward the asymmetric
Mukaiyama-Mannich reaction of imines with ketene silyl acetals leading to beta
amino acid esters in good yields (up to 99%) with high diastereoselectivities
(syn/anti up to 97:3) and enantioselectivities (up to 98% ee). The long-standing
problem of the chiral phosphoric acid-catalyzed asymmetric Mukaiyama-Mannich
reaction that requires a 2-hydroxyphenyl moiety was solved by this disulfonimide
catalyst.
PMID- 27610633
TI - SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.
AB - Post-translational modifications (PTMs) regulate numerous proteins and are
important for many biological processes. Lysine 4-oxononanoylation (4-ONylation)
is a newly discovered histone PTM that prevents nucleosome assembly under
oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from
histones remains unknown, which hampers the further investigation of the cellular
function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from
histones and other proteins in live cells. A crystal structure of SIRT2 in
complex with a 4-ONyl peptide reveals a lone pair-pi interaction between Phe119
and the ketone oxygen of the 4-ONyl group. This is the first time that a
mechanism to reverse 4-ONyl lysine modification is reported and will help to
understand the role of SIRT2 in oxidative stress responses and the function of 4
ONylation.
PMID- 27610635
TI - Separation of Storage and Loss Modulus of Polyelectrolyte Multilayers on a
Nanoscale: A Dynamic AFM Study.
AB - Atomic force microscopy (AFM) is used to carry out rheology measurements on the
nanoscale and to determine the mechanical properties of poly(l-lysine)
(PLL)/hyaluronic acid (HA) multilayer films. Storage (G') and loss modulus (G")
of the films are calculated and compared with the values obtained from quartz
crystal microbalance with dissipation monitoring measurements (QCM-D). A
predominant elastic behavior independently of the applied frequencies (5-100 Hz)
is observed for native HA/PLL films consisting of 36 double layer. If the layers
are cross-linked, the value of G' increases by 2 orders of magnitude, while the
loss modulus becomes negligible, making these films a purely elastic chemical
gel. The values of G' and G'' extracted from QCM-D measurements on native films
are much higher, due to the different frequency regime of the applied shear
stress. However, the viscoelastic ratio from the two methods is the same and
proves the elastic dominated response of the multilayer in both frequency
regimes.
PMID- 27610636
TI - Welcome message - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw,
Poland.
PMID- 27610637
TI - Presidential message - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw,
Poland.
PMID- 27610638
TI - Boards and Committees - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw,
Poland.
PMID- 27610639
TI - Scientific Program - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw,
Poland.
PMID- 27610640
TI - Oral presentations - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw,
Poland.
AB - Abstracts from the XLIII Congress of the European Society for Artificial Organs,
14-17 September 2016, Warsaw, Poland.
PMID- 27610641
TI - Posters - XLIII Annual ESAO Congress, 14-17 September 2016, Warsaw, Poland.
AB - Abstracts from the XLIII Congress of the European Society for Artificial Organs,
14-17 September 2016, Warsaw, Poland.
PMID- 27610642
TI - Advances of recurrent risk factors and management of choledocholithiasis.
AB - Gallstone disease is a common and frequently occurring disease in human, and it
is the main disease among the digestive system diseases. The incidence of
gallstone disease in western countries is about 5%-22%, and common bile duct
stones (CBDS) accounts for 8%-20%. CBDS easily lead to biliary obstruction,
secondary cholangitis, pancreatitis, and obstructive jaundice, even endanger
life. Therefore, it needs timely treatment once diagnosed. The recurrence of
choledocholithiasis after bile duct stones clearance involves complicated factors
and cannot be completely elaborated by a single factor. The risk factors for
recurrence of choledocholithiasis include bacteria, biliary structure, endoscopic
and surgical treatment, and inflammation. The modalities for management of
choledocholithiasis are endoscopic retrograde cholangiopancreatography (ERCP),
laparoscopic or open common bile duct exploration, dissolving solutions,
extracorporeal shockwave lithotripsy (ESWL), percutaneous radiological
interventions, electrohydraulic lithotripsy (EHL) and laser lithotripsy. We
compare the different benefits between surgery and ERCP. And finally, we make a
summary of the current strategy for reducing the recurrence of CBDS and future
perspectives for CBDS management.
PMID- 27610643
TI - Do More With Less: Tips and Techniques for Maximizing Small Biopsy and Cytology
Specimens for Molecular and Ancillary Testing: The University of Colorado
Experience.
AB - Context .- In an era in which testing of patient tumor material for molecular and
other ancillary studies is of increasing clinical importance for selection of
therapy, the ability to test on small samplings becomes critical. Often, small
samplings are rapidly depleted in the diagnostic workup or are insufficient for
multiple ancillary testing approaches. Objective .- To describe technical
methodologies that can be implemented to preserve and maximize tissue for
molecular and other ancillary testing. Data Sources .- Retrospective analysis of
a case cohort from the University of Colorado, description of techniques used at
the University of Colorado, and published literature. Conclusions .- Numerous
techniques can be deployed to maximize molecular and other ancillary testing,
even when specimens are from small samplings. A dedicated process for molecular
prioritization has a high success rate, but also increases workload, which must
be factored into establishing such a process. Additionally, establishing high
fidelity communication strings is critical for success of dedicated molecular
prioritization of samples. Numerous approaches can be deployed for alternative
specimen types, and several technical approaches can also aid in maximizing small
specimens.
PMID- 27610644
TI - Development and Validation of an ERCC1 Immunohistochemistry Assay for Solid
Tumors.
AB - CONTEXT: - Excision repair cross-complementation 1 (ERCC1) is a key enzyme in
nuclear excision repair pathway and has a critical role in helping remove DNA
adducts caused by cross-linking agents, such as platinum-containing cancer
chemotherapies and other DNA-damaging therapeutic modalities. ERCC1 expression,
evaluated by techniques such as immunohistochemistry, has been associated with
clinical response; ERCC1+ tumors are more resistant to cisplatin treatment than
are ERCC1- tumors. Although several immunohistochemistry, anti-ERCC1 antibodies
are available, the 8F1 clone, in particular, has been used in many studies.
Recent evidence has suggested that the 8F1 antibody cross-reacts with at least
one other protein, raising concerns about the specificity of this clone.
OBJECTIVE: - To design an immunohistochemistry assay to detect ERCC1 levels that
show dynamic range and consistent analytic performance. DESIGN: - Two different
primary antibodies to ERCC1, clones 4F9 and D6G6, were evaluated on formalin
fixed, paraffin-embedded tissue. We then performed a fit-for-purpose assay
validation with the 4F9 clone, which included sensitivity assessment across
several solid tumor types and evaluation of analytic parameters, such as
precision and reproducibility. RESULTS: - The 4F9 clone was consistently superior
to the D6G6 clone in the optimization phase. A range of expression was seen in
ovarian, head and neck, non-small cell lung, and esophageal cancer samples when
tested with the 4F9 clone. The antibody showed acceptable reproducibility
(31.02%) and precision (16.06%). CONCLUSIONS: - This assay can be used to assess
ERCC1 levels during clinical studies of patient tumors from a variety of tumor
types.
PMID- 27610645
TI - Surgical Specimen Management: A Descriptive Study of 648 Adverse Events and Near
Misses.
AB - CONTEXT: - Surgical specimen adverse events can lead to delays in treatment or
diagnosis, misdiagnosis, reoperation, inappropriate treatment, and anxiety or
serious patient harm. OBJECTIVES: - To describe the types and frequency of event
reports associated with the management of surgical specimens, the contributing
factors, and the level of harm associated with these events. DESIGN: - A
retrospective review was undertaken of surgical specimen adverse events and near
misses voluntarily reported in the University HealthSystem Consortium Safety
Intelligence Patient Safety Organization database by more than 50 health care
facilities during a 3-year period (2011-2013). Event reports that involved
surgical specimen management were reviewed for patients undergoing surgery during
which tissue or fluid was sent to the pathology department. RESULTS: - Six
hundred forty-eight surgical specimen events were reported in all stages of the
specimen management process, with the most common events reported during the
prelaboratory phase and, specifically, with specimen labeling,
collection/preservation, and transport. The most common contributing factors were
failures in handoff communication, staff inattention, knowledge deficit, and
environmental issues. Eight percent of the events (52 of 648) resulted in either
the need for additional treatment or temporary or permanent harm to the patient.
CONCLUSIONS: - All phases of specimen handling and processing are vulnerable to
errors. These results provide a starting point for health care organizations to
conduct proactive risk analyses of specimen handling procedures and to design
safer processes. Particular attention should be paid to effective communication
and handoffs, consistent processes across care areas, and staff training. In
addition, organizations should consider the use of technology-based
identification and tracking systems.
PMID- 27610646
TI - Interobserver Agreement of Usual Interstitial Pneumonia Diagnosis Correlated With
Patient Outcome.
AB - CONTEXT: - The histopathologic criteria for idiopathic pulmonary fibrosis were
revised in the American Thoracic Society/European Respiratory Society/Japan
Respiratory Society/Latin American Thoracic Association guidelines in 2011.
However, the evidence of diagnosis based on the guidelines needs further
investigation. OBJECTIVE: - To examine whether the revised histopathologic
criteria for idiopathic pulmonary fibrosis improved interobserver agreement among
pathologists and the predicted prognosis in patients with interstitial pneumonia.
DESIGN: - Twenty, consecutive, surgical lung-biopsy specimens from cases of
interstitial pneumonia were examined for histologic patterns by 11 pathologists
without knowledge of clinical and radiologic data. Diagnosis was based on
American Thoracic Society/European Respiratory Society guidelines of 2002 and
2011. Pathologists were grouped by cluster analysis, and interobserver agreement
and association to the patient prognosis were compared with the diagnoses for
each cluster. RESULTS: - The generalized kappa coefficient of diagnosis for all
pathologists was 0.23. If the diagnoses were divided into 2 groups: usual
interstitial pneumonia (UIP)/probable UIP (the UIP group) or possible/not UIP
(the non-UIP group), according to the 2011 guidelines, the kappa improved to
0.37. The pathologists were subdivided into 2 clusters in which 1 showed an
association between UIP group diagnosis and patient prognosis (P < .05).
CONCLUSIONS: - Agreement about pathologic diagnosis of interstitial pneumonia is
low; however, results after division into UIP and non-UIP groups provided
favorable agreement. The cluster analysis revealed 1 of the 2 clusters providing
high interobserver agreement and prediction of patient prognosis.
PMID- 27610647
TI - Targeted Next-Generation Sequencing Successfully Detects Causative Genes in
Chinese Patients with Hereditary Hearing Loss.
AB - AIMS: We attempted to identify the genetic epidemiology of hereditary hearing
loss among the Chinese Han population using next-generation sequencing (NGS).
MATERIALS AND METHODS: The entire length of the genes GJB2, SLC26A4, and GJB3, as
well as exons of 57 additional candidate genes were sequenced from 116
individuals suffering from hearing loss. RESULTS: Thirty potentially causative
mutations from these 60 genes were identified as the likely etiologies of hearing
loss in 67 of the cases. In our study, SLC26A4 and GJB2 were the most frequently
affected genes among the Chinese Han population with hearing loss. Collectively,
they account for 52.8% of the cases, followed by MTRNR1, PCDH15, and TECTA. These
data also illustrate that NGS can be used to identify rare alleles responsible
for hereditary hearing loss: 22 of the 30 (73.3%) genes identified with mutations
are rarely mutated in hereditary hearing loss and only account for 21.5% (42/195)
of the total mutation frequency, explaining no more than 2% for each gene. These
rarely mutated genes would be missed by conventional diagnostic sequencing
approaches. CONCLUSIONS: NGS can be used effectively to identify both the common
and rare genes causing hereditary hearing loss.
PMID- 27610649
TI - MRI-based reference range for the renal pelvis anterior-posterior diameter in
children ages 0-19 years.
AB - OBJECTIVE: To determine the mean and normal range of anteroposterior diameter
(APD) of the renal pelves in children. METHODS: Patients aged 0-19 years with
normal spinal MRIs were identified after institutional review board approval.
Those with dilating uropathy or abdominal surgery/radiation were excluded. The
maximum APD was measured. A mixed linear model was fit to determine the
relationship between APD and age, adjusted for bladder distention. The left and
right kidneys were treated independently. RESULTS: 283 left and 285 right renal
units were included. For the left, a 3.5% increase in APD per year was predicted
(p < 0.0001), with the average APD for infants and 18-year olds with non
distended bladders being 2.5 mm (95th percentile: 7.2 mm) and 4.6 mm (13.4 mm),
respectively. For the right, a 3.9% increase in APD per year was predicted (p <
0.0001), with the average APD for infants and 18-year olds with non-distended
bladders being 2.8 mm (8.4 mm) and 5.5 mm (16.6 mm), respectively. Compared with
a non-distended bladder, a distended bladder increased the predicted APD between
23% (right) and 38% (left) (p = 0.01 and p < 0.0001, respectively). CONCLUSION:
The mean and normal ranges of APD measured by MRI in children are provided. APD
increases with age and bladder distension and is greater on the left. Advances in
knowledge: This article establishes normative ranges for APD, a critical
component of genitourinary tract evaluation, and does so using the most precise
imaging modality for this condition.
PMID- 27610651
TI - Effect of hydraulic retention time on suppression of methanogens during a
continuous biohydrogen production process using molasses wastewater.
AB - This study was undertaken to investigate the reduction of the hydraulic retention
time (HRT) to decrease methane generation and recover hydrogen production during
the long-term operation of biohydrogen production in a continuous stirred tank
reactor (CSTR) using molasses wastewater. Reduction of HRT can be a simple and
economic method to immediately control unfavorable methane generated during
continuous operation of a hydrogen production system. The steady-state
performance of the CSTR showed a hydrogen content of 41.3 +/- 3.30% and a
hydrogen production rate (HPR) of 63.7 +/- 10.01 mmol-H2L-1d-1 under an organic
loading rate (OLR) of 29.7 g CODL-1 at an HRT of 24 h. Increase in the methane
level above 40% during long-term operation caused decrease in the hydrogen
content and HPR to 5.9 +/- 1.6% and 2.1 +/- 1.1 mmoL-H2L-1d-1, respectively. When
methane increased to a high level over 40%, the CSTR at the HRT of 24 h was
operated at the HRT of 12 h. Reduction of the HRT from 24 to 12 h led to decrease
in the methane content of 12.1 +/- 4.44% and recovery of the HPR value to 48.9 +/
15.37 mmol-H2L-1d-1 over a duration of 13-22 d. When methane is generated in a
continuously operated reactor, reduction of the HRT can be an easy way to
suppress methanogens and recover hydrogen production without any additives or
extra treatments.
PMID- 27610652
TI - Hypoxia-Dependent HIF-1 Activation Impacts on Tissue Remodeling in Graves'
Ophthalmopathy-Implications for Smoking.
AB - CONTEXT: In Graves' ophthalmopathy (GO), inflammation with tissue expansion in a
closed compartment like the bony orbit and smoking may cause tissue hypoxia.
OBJECTIVES: In this study, we investigated whether hypoxia-inducible factor-1
(HIF-1) action impacts on tissue remodeling in GO with the aim to identify
possible new therapeutic targets. DESIGN/SETTING/PARTICIPANTS: Orbital
fibroblasts (OFs) were derived from GO patients and control (Ctrl) persons. We
analyzed HIF-1alpha levels in response to hypoxia and cigarette smoke extract, as
well as HIF-1-dependent vascular endothelial growth factor (VEGF) release and
adipogenic differentiation, by using HIF-1alpha small interfering RNA, or HIF-1
inhibitor BAY 87-2243. MAIN OUTCOME MEASURES: Western blot, real-time PCR, ELISA,
and immunohistochemistry were used to analyze HIF-1alpha, VEGF, CD31, and
adiponectin. Adipogenic differentiation was measured with Nile red assay.
RESULTS: Higher HIF-1alpha levels in OFs were correlated with the clinical
activity score of GO patients. Cigarette smoke extract elevated HIF-1alpha
levels. HIF-1-dependent VEGF secretion was enhanced in GO-OF compared to Ctrl-OF,
and as an in vivo consequence, we found a higher vessel density in GO tissue than
in Ctrl tissue. Hypoxia strongly stimulated HIF-1-dependent adipogenesis and
adiponectin release of GO-OF and enhanced TSH receptor-mediated adipogenesis.
CONCLUSIONS: Hypoxia impacts on tissue remodeling in GO by stimulating
angiogenesis and adipogenesis through activation of HIF-1-dependent pathways in
OFs. Our results offer a molecular mechanism for the detrimental influence of
smoking on GO and an explanation as to why decompression can improve the outcome
of patients. Drug-targeted inhibition of HIF-1/VEGF may provide a therapeutic
option to control tissue expansion in GO.
PMID- 27610650
TI - Target-independent variable region mediated effects on antibody clearance can be
FcRn independent.
AB - The importance of the neonatal Fc receptor (FcRn) in extending the serum half
life of monoclonal antibodies (mAbs) is well demonstrated, and has led to the
development of multiple engineering approaches designed to alter Fc interactions
with FcRn. Recent reports have additionally highlighted the effect of nonspecific
interactions on antibody pharmacokinetics (PK), suggesting an FcRn-independent
mechanism for mAb clearance. In this report we examine a case study of 2 anti
interleukin-12/23 antibodies, ustekinumab and briakinumab, which share the same
target and Fc, but differ in variable region sequences. Ustekinumab displayed
near baseline signal in a wide range of early stage developability assays for
undesirable protein/protein interactions, while briakinumab showed significant
propensity for self- and cross-interactions. This phenotypic difference
correlates with faster clearance rates for briakinumab in both human FcRn
transgenic and FcRn knockout mice. These findings support a dominant contribution
for FcRn-independent clearance for antibodies with high nonspecificity, and
highlight a key role for early stage developability screening to eliminate clones
with such high nonspecific disposition PK.
PMID- 27610653
TI - Spontaneous Hypoglycemia After Islet Transplantation: The Case For Using Non
Hepatic Sites.
AB - This Perspective provides a brief history of intrahepatic alloislet and autoislet
transplantation in humans and an update of the recent success rates. It also
examines the important role that hypoglycemia plays in clinical outcomes. On the
one hand, recurrent serious hypoglycemic episodes related to insulin therapy are
a major criterion for alloislet transplantation. On the other hand, spontaneous
clinical hypoglycemia, perhaps related to the accompanying Roux-en-Y procedure
for total pancreatectomy, is a complication of autoislet transplantation. Complex
alterations in glucagon secretion compromise counter-regulation of hypoglycemia
in both situations. The glucagon response to hypoglycemia is intrinsically
defective in type 1 diabetes before transplant because of the absence of
physiological regulation of alpha-cell secretion by neighboring beta-cells.
Glucagon secretion from intrahepatic islets during systemic hypoglycemia is also
defective, although beta-cells in the graft are normally regulated by glucose and
arginine. My personal perspective is that the latter is caused by intrahepatic
glycogenolysis stimulated by systemic hypoglycemia with consequent increases in
intrahepatic glucose flux, which incorrectly signals intrahepatic alpha-cells to
be quiescent. This defect is liver-specific, which strongly suggests modifying
the current approach to islet transplantation by placing a portion of allo- and
autoislets in nonhepatic sites in addition to hepatic sites to ensure
physiological glucagon secretion as a strategy to ameliorate post-transplant
hypoglycemia.
PMID- 27610694
TI - Focusing on the Obvious, the Elephant: Livingood and Colleagues Respond.
PMID- 27610695
TI - Psychosocial screening for patients with prostate cancer: The development and
validation of the psychosocial distress questionnaire-prostate cancer.
AB - We describe the psychosocial distress questionnaire-prostate cancer (PDQ-PC), a
psychosocial screening list developed and validated specifically for prostate
cancer patients. An existing screening list, the psychosocial distress
questionnaire-breast cancer (PDQ-BC), was used as a starting point. Two focus
groups were then implemented to investigate which items of the PDQ-BC were
relevant for the PDQ-PC and which new items were needed. Validity and reliability
of the questionnaire were assessed on 278 prostate cancer patients. Factor
analysis showed that the 36-item PDQ-PC comprises eight subscales, for which the
internal consistency ranged from alpha = 0.48-0.88. Moreover, moderate to high
convergent validity was found.
PMID- 27610697
TI - How Do People Stop Non-Suicidal Self-Injury? A Systematic Review.
AB - : The current paper reviews extant quantitative and qualitative literature into
how Non-Suicidal Self-Injury cessation occurs, and individuals' experiences of
stopping. Specific search criteria utilizing a PRISMA format were used across 5
databases, which resulted in 454 papers being identified. After utilizing
exclusion criteria and then review, nine of the 454 papers identified were
retained for extensive synthesis and critique. RESULTS: Results from 8 of the
identified papers indicated that both intra and inter personal factors can
influence self-injury cessation. These include: family support, self-esteem,
emotional regulation, and professional help. Only 1 paper articulated a cessation
process, describing it as a procedural event of developing interpersonal
strength, then implementing alternative coping strategies. Limitations and
implications of the studies are reported, concluding that further research is
warranted to inform effective prevention and treatment strategies to ameliorate
this growing public health concern.
PMID- 27610696
TI - Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.
AB - BACKGROUND: The cyclin-dependent-kinase inhibitors (CDKN)/retinoblastoma (RB1)
pathway has been implicated as having a role in medullary thyroid carcinoma (MTC)
tumorigenesis. CDKN2C loss has been associated with RET-mediated MTC in humans
but with minimal phenotypic correlation provided. The objective of this study was
to evaluate the association between tumor RET mutation status, CDKN2C loss, and
aggressiveness of MTC in a cohort of patients with sporadic disease. METHODS:
Tumors from patients with sporadic MTC treated at a single institution were
evaluated for somatic RETM918T mutation and CDKN2C copy number loss. These
variables were compared to patient demographics, pathology detail, clinical
course, and disease-specific and overall survival. RESULTS: Sixty-two MTC cases
with an initial surgery date ranging from 1983 to 2009 met the inclusion
criteria, of whom 36 (58%) were male. The median age at initial surgery was 53
years (range 22-81 years). The median tumor size was 30 mm (range 6-145 mm) with
29 (57%) possessing extrathyroidal extension. Nodal and/or distant metastasis at
presentation was found in 47/60 (78%) and 12/61 (20%) patients, respectively.
Median follow-up time was 10.5 years (range 1.1-27.8 years) for the censored
observations. The presence of CDKN2C loss was associated with worse M stage and
overall AJCC stage. Median overall survival of patients with versus without
CDKN2C loss was 4.14 [confidence interval (CI) 1.93-NA] versus 18.27 [CI 17.24
NA] years (p < 0.0001). Median overall survival of patients with a combined
somatic RETM918T mutation and CDKN2C loss versus no somatic RETM918T mutation and
CDKN2C loss versus somatic RETM918T mutation and CDKN2C 2N versus no somatic
RETM918T mutation and CDKN2C 2N was 2.38 [CI 1.67-NA] years versus 10.81 [CI 2.46
NA] versus 17.24 [CI 9.82-NA] versus not reached [CI 13.46-NA] years (p <
0.0001). CONCLUSIONS: The detection of somatic CDKN2C loss is associated with the
presence of distant metastasis at presentation as well decreased overall
survival, a relationship enhanced by concomitant RETM918T mutation. Further
defining the genes involved in the progression of metastatic MTC will be an
important step toward identifying pathways of disease progression and new
therapeutic targets.
PMID- 27610699
TI - Radial Head and Neck Allograft for Comminute Irreparable Fracture-Dislocations of
the Elbow.
AB - Fracture-dislocations of the elbow can be difficult to treat, with unsatisfactory
results in some cases. In general, it is preferable to preserve the fractured
radial head when possible, but some patients present a unique treatment challenge
because of extremely comminuted fractures and bone loss. In these cases, the only
options available are radial head prosthesis or allograft. The authors present a
case of a 45-year-old man with a fracture-dislocation of the left elbow that was
treated with an allograft of the radial head and neck because of extreme
comminution of the fracture. There have been a few reports about osteochondral
allograft transplantation of the radial head, and they all included traumatic or
posttraumatic cases treated with a frozen allograft. To the best of the authors'
knowledge, this is the first report on the use of osteochondral allograft in the
acute setting for the treatment of a comminuted fracture of the radius involving
the whole head and neck. The clinical results were satisfactory at the final
follow-up, although mild degenerative changes were present, the screws were
coming loose, and the radial head had a slight valgus deformity. Radial head
allograft can be an option in selected cases of acute fractures with severe
comminution and bone loss that are not amenable to a stable internal fixation;
for the young and active patient, who is not the best candidate for radial head
resection; or in cases in which radial head arthroplasty is not feasible because
of severe bone loss. [Orthopedics. 2016; 39(6):e1205-e1208.].
PMID- 27610698
TI - Reducing Variability in Orthogonal Reformatted Image Quality Associated With
Axial Long-z-Axis CT Angiography.
AB - OBJECTIVE: The objective of our study was to reduce variation in image quality of
orthogonal reformatted images generated from long-z-axis CT angiography (CTA)
studies of the upper and lower extremities. SUBJECTS AND METHODS: Upper and lower
extremity CTA studies were targeted at a single health care system. A correctly
performed CTA examination was defined as one that met the following three
criteria: Sagittal and coronal reformats were obtained, a high-resolution matrix
greater than 512 * 512 was used, and reformatted images were available in a
distance-measurable format. Baseline data were collected from February 1, 2014,
through September 30, 2014. Corrective actions were implemented during three
consecutive plan-do-check-act (PDCA) cycles from October 1, 2014, through July
31, 2015, that addressed human, technical, and systematic variations. A 3-month
maintenance period followed in which no intervention was performed. Longitudinal
data were analyzed monthly using a statistical process control chart (p-chart).
RESULTS: The total number of long-z-axis extremity CTA studies analyzed was as
follows: 351 CTA studies were analyzed at baseline, 94 at the first PDCA cycle,
92 at the second PDCA cycle, 114 at the third PDCA cycle, and 138 during the
maintenance period. The monthly rate of correctly performed studies ranged from
7% to 51% (mean, 38% +/- 13% [SD]) during the baseline period, 32-59% (mean, 46%
+/- 14%) during the first PDCA cycle, 40-81% (mean, 61% +/- 21%) during the
second PDCA cycle, and 80-82% (mean, 81% +/- 0.9%) during the third PDCA cycle.
The monthly rate improved to 90-91% (mean, 91% +/- 0.5%) during the maintenance
period. The upper and lower control limits of the p-chart were upshifted after
the second and third PDCA cycles. Correcting systematic and technical variations
led to the greatest improvements in reformat accuracy. CONCLUSION: Obtaining
consistently and correctly reformatted images from long-z-axis CTA studies is
achievable using iterative PDCA cycles.
PMID- 27610700
TI - Orthopedic Surgeons' Management of Elective Surgery for Patients Who Use
Nicotine.
AB - Despite significant research documenting the detrimental effects of tobacco, the
orthopedic literature lacks evidence regarding how surgeons alter their
management of elective surgery when patients use nicotine. To better understand
how patients' use of nicotine influences orthopedic surgeons' pre- and
postoperative management of elective surgery, a 9-question paper survey was
distributed at the 2012 annual meeting of the American Academy of Orthopaedic
Surgeons among attending US orthopedic surgeons, including general orthopedists
and specialty-trained orthopedic surgeons. Survey questions focused on attitudes
and practice management regarding patients who use nicotine. Using a chi-square
test, no statistically significant variation was observed between subspecialists
and general orthopedists or among different subspecialties. Ninety-eight percent
of the orthopedic surgeons surveyed counseled tobacco users about the adverse
effects of nicotine. However, approximately half of all of the respondents spent
less than 5 minutes on perioperative nicotine counseling. Forty-one percent of
all of the respondents never delayed elective surgery because of a patient's
nicotine use, followed closely by 39% delaying surgery for less than 3 months.
Subspecialty had little influence on how orthopedic surgeons managed nicotine
users. The high rate of counseling on the adverse effects of nicotine suggested
agreement regarding the detrimental effects of smoking. However, the study
population infrequently delayed surgery or used smoking cessation measures.
Studies are needed to determine why few surgeons frequently alter the management
of nicotine users and what modifications in orthopedic practice could improve
outcomes for these patients. [Orthopedics. 2017; 40(1):e90-e94.].
PMID- 27610701
TI - A Custom-made Acetabular Implant for Paprosky Type 3 Defects.
AB - Acetabular revision is a challenging operation, especially when dealing with
major bone loss and poor bone quality. This article describes a detailed approach
to defect analysis, including measurement of bone deficiency and bone quality. A
custom-made titanium implant, with precisely outlined flanges to the host bones
of the ilium, ischium, and pubis, taking into account the bone quality for
optimal screw purchase, was used to reconstruct the acetabular defect.
Preliminary results for 12 patients who were retrospectively reviewed after a
minimum follow-up of 18 months were promising. [Orthopedics. 2017; 40(1):e195
e198.].
PMID- 27610702
TI - Radial Shaft Reconstruction With an Intercalary Endoprosthesis Following
Resection of Metastatic Tumor.
AB - Improvements in imaging and treatment of musculoskeletal tumors have increased
the variety of options for reconstruction following joint-sparing diaphyseal
resection. The purpose of this case series was to show that reconstruction of
malignant tumors of the radial shaft with an intercalary prosthesis may be an
option for patients with segmental bone loss. Three consecutive patients
underwent wide resection of the radial diaphysis followed by reconstruction with
a custom intercalary prosthesis. A custom intercalary prosthesis with lap joint
design was used in all 3 cases. Mean follow-up was 18 months (range, 9-25
months). All patients were weight bearing as tolerated 1 week postoperatively. At
the most recent follow-up, patients' mean elbow flexion and extension arc was 137
degrees (range, 130 degrees -140 degrees ). At the forearm, mean supination was
60 degrees (range, 30 degrees -90 degrees ) and mean pronation was 70 degrees
(range, 60 degrees -90 degrees ). At the wrist, mean palmar flexion was 80
degrees (range, 70 degrees -90 degrees ) and mean dorsiflexion was 80 degrees
(range, 70 degrees -90 degrees ). All patients reported minimal to no pain and no
significant functional limitations. Mean Musculoskeletal Tumor Society score was
26/30 (87%). Reconstruction with an intercalary prosthesis is a viable option for
patients with metastatic disease of the radial shaft. All patients had
satisfactory results and early return to function; none required return to the
operating room. Possible advantages of reconstruction with an intercalary
prosthesis compared with reconstruction with a bone graft or
polymethylmethacrylate osteosynthesis include early return to function and
minimal weight-bearing restrictions postoperatively. [Orthopedics. 2017;
40(2):e242-e247.].
PMID- 27610704
TI - 3D Printing of Cantilever-Type Microstructures by Stereolithography of
Ferromagnetic Photopolymers.
AB - In the present work, prototypes of polymeric cantilever-based magnetic
microstructures were fabricated by means of stereolithography (SL). To this end,
a UV-curable system suitable for high-resolution SL-processing was formulated by
blending a bifunctional acrylic monomer with photoinitiator and visible dye whose
content was tuned to tailor resin SL sensitivity. Subsequently, to confer
ferromagnetic properties to the photopolymer, two different strategies were
implemented. A two-step approach involved selective deposition of a metal layer
on photopolymer SL-cured surfaces through an electroless plating process. On the
other hand, SL-processable ferromagnetically responsive nanocomposites (FRCs)
were obtained by directly loading magnetite nanoparticles within the photopolymer
matrix. In order to achieve high-printing resolution, resin SL sensitivities were
studied as a function of the various additives contents. Photocalorimetric
analyses were also performed to investigate the photopolymer conversion
efficiency upon light exposure. High-performing formulations were characterized
by reduced penetration depth (<50 MUm) and small critical energies thus enabling
for fast printing of micrometric structures. Finally, the self-standing
characteristics of the resin combined with the layered-fashion deposition typical
of the 3D printing technologies were exploited for the fabrication of cantilever
(CL)-based beams presented as possible magnetic sensors. As a demonstration of
the feasibility of the two approaches, the magnetic beams were successfully
actuated and their sensing performances in terms of static deflection vs applied
magnetic field applied were qualitatively studied. Being not restricted to CL
based geometries, the combination of SL-printing with the formulation of novel
smart photopolymers open the way toward the fabrication of high-customized
complex 3D models integrating functional microstructures.
PMID- 27610703
TI - Use of a Pin Distractor as an Aid for Fixation of Pronation-External Rotation
Fibular Fractures.
AB - Restoration of fibular length in pronation and other comminuted ankle fractures
is key to good clinical outcomes and is often a challenging aspect of open
reduction and internal fixation of the fibula. This article reports the use of a
pin distractor to achieve appropriate fibular reduction in otherwise challenging
ankle fractures. The authors describe the use of a pin distractor to obtain
length and minimize the number of surgical assistants needed for these
challenging ankle fractures. The authors find this technique particularly useful
with pronation type and subacute ankle fractures. [Orthopedics. 2017; 40(1):e192
e194.].
PMID- 27610705
TI - Posttranslational Modifications of Red Blood Cell Ghost Proteins as "Signatures"
for Distinguishing between Low- and High-Risk Myelodysplastic Syndrome Patients.
PMID- 27610706
TI - Molecularly Imprinted Membranes: Past, Present, and Future.
AB - More than 80 years ago, artificial materials with molecular recognition sites
emerged. The application of molecular imprinting to membrane separation has been
studied since 1962. Especially after 1990, such research has been intensively
conducted by membranologists and molecular imprinters to understand the
advantages of each technique with the aim of constructing an ideal membrane,
which is still an active area of research. The present review aims to be a
substantial, comprehensive, authoritative, critical, and general-interest review,
placed at the cross section of two broad, interconnected, practical, and
extremely dynamic fields, namely, the fields of membrane separation and
molecularly imprinted polymers. This review describes the recent discoveries that
appeared after repeated and fertile collisions between these two fields in the
past three years, to which are added the worthy acknowledgments of pioneering
discoveries and a look into the future of molecularly imprinted membranes. The
review begins with a general introduction in membrane separation, followed by a
short theoretical section regarding the basic principles of mass transport
through a membrane. Following these general aspects on membrane separation, two
principles of obtaining polymeric materials with molecular recognition properties
are reviewed, namely, molecular imprinting and alternative molecular imprinting,
followed the methods of obtaining and practical applications for the particular
case of molecularly imprinted membranes. The review continues with insights into
molecularly imprinted nanofiber membranes as a promising, highly optimized type
of membrane that could provide a relatively high throughput without a
simultaneous unwanted reduction in permselectivity. Finally, potential
applications of molecularly imprinted membranes in a variety of fields are
highlighted, and a look into the future of membrane separations is offered.
PMID- 27610707
TI - Newly Designed Graphene Cellular Monolith Functionalized with Hollow Pt-M (M =
Ni, Co) Nanoparticles as the Electrocatalyst for Oxygen Reduction Reaction.
AB - Newly designed graphene cellular monoliths (GCMs) functionalized with hollow Pt-M
nanoparticles (NPs) (Pt-M/GCM, M = Ni, Co) have been successfully achieved by a
facile and powerful method on the basis of sonochemical-assisted reduction and
gelatinization processes. First, hollow Pt-M (M = Ni, Co) NPs were synthesized
and distributed on graphene oxide sheets (Pt-M/GO) by sodium borohydride
reduction of metal precursors in the ultrasonic environment. Second, the hollow
structure was further formed by ascorbic acid (AA) reduction of Pt precursors in
gelatinization process. Meanwhile, GO sheets with hollow Pt-M NPs were reduced to
graphene, and were assembled into Pt-M/GCM hydrogels by gelatinization process.
The Pt-M/GCM (M = Ni, Co) electrocatalysts have a factor of 9.4-18.9 enhancement
in electrocatalytic activity and higher durability toward oxygen reduction
reaction (ORR), compared with those of commercial Pt/C catalyst. In detail, the
mass activities for Pt-Ni/GCM and Pt-Co/GCM are 1.26 A mgPt-1 and 1.79 A mgPt-1,
respectively; meanwhile, the corresponding specific activities are 1.03 and 2.08
mA cm-2. The successful synthesis of such attractive materials paves the way to
explore a series of porous materials in widespread applications.
PMID- 27610708
TI - Novel Electrochemical Raman Spectroscopy Enabled by Water Immersion Objective.
AB - Electrochemical Raman spectroscopy is a powerful molecular level diagnostic
technique for in situ investigation of adsorption and reactions on various
material surfaces. However, there is still a big room to improve the optical path
to meet the increasing request of higher detection sensitivity and spatial
resolution. Herein, we proposed a novel electrochemical Raman setup based on a
water immersion objective. It dramatically reduces mismatch of the refractive
index in the light path. Consequently, significant improvement in detection
sensitivity and spatial resolution has been achieved from both Zemax simulation
and the experimental results. Furthermore, the thickness of electrolyte layer
could be expanded to 2 mm without any influence on the signal collection. Such a
thick electrolyte layer allows a much normal electrochemical response during the
spectroelectrochemical investigations of the methanol oxidation.
PMID- 27610709
TI - Controlled Interconversion of Superposed-Bistriangle, Octahedron, and
Cuboctahedron Cages Constructed Using a Single, Terpyridinyl-Based Polyligand and
Zn(2.).
AB - Metallomacromolecular architectural conversion is expanded by the
characterization of three different structures. A quantitative, single-step, self
assembly of a shape-persistent monomer, containing a flexible crown ether moiety,
gives an initial Archimedean-based cuboctahedron that has been unequivocally
characterized by 1D and 2D NMR spectroscopy, mass spectrometry, and collision
cross section analysis. Both dilution and exchange of counterions, transforms
this cuboctahedron into two identical octahedrons, which upon further dilution
convert into four, superposed, bistrianglar complexes; increasing the
concentration reverses the process. Ion binding studies using the cuboctahedral
cage were undertaken.
PMID- 27610710
TI - Interactions of Nanosized Aggregates of Fullerene C60 with Electrolytes in
Methanol: Coagulation and Overcharging of Particles.
AB - Contrary to numerous studies on the stability of fullerene aqueous colloidal
solutions in the presence of electrolytes, the corresponding issue for the
organosols was until recently almost unexplored. In this article, the state of
C60 in methyl alcohol and the regularities of the coagulation of colloidal
solution in this solvent were examined in the presence of electrolytes. Alcosols
with a fullerene concentration of 4 * 10-6 M were prepared by the dilution of the
C60 saturated solution in toluene by methanol. The ca. 300 nm-sized aggregates
possess a negative electrokinetic potential value, zeta = -37 +/- 8 mV. To
determine the critical coagulation concentrations, CCC, the size increase of the
species was followed up using the dynamic light scattering method. The analysis
of the coagulation in terms of the Fuchs function, W, was accompanied by zeta
potential monitoring. The consideration of the data for 1:1 electrolytes NaClO4
and N(n-C4H9)4ClO4 allows a rough estimate of the Hamaker constant of fullerene
fullerene attraction. Whereas in the case of these two electrolytes the colloidal
species are negatively charged at the CCC, expressed overcharging of up to zeta =
+36 mV by H+, Ca2+, Ba2+, and La3+ ions was observed. The action of HClO4 should
be attributed to the interfacial acid-base reaction, whereas the excessive
attraction of metal cations is caused by poor solvation in methanol; the negative
charge is restored when the metal cations are shielded by a macrocyclic ligand.
PMID- 27610711
TI - Cleavable beta-Cyanoethyl Isocyanide in the Ugi Tetrazole Reaction.
AB - beta-Cyanoethyl isocyanide is introduced as a cleavable isocyanide in the Ugi
tetrazole reaction. Eleven examples are described that exhibit a broad scope and
are obtained in good overall yields. The obtained 1H-tetrazole scaffold is an
important bioisostere for carboxylic acids, and the method described here is a
valuable alternative route to known procedures.
PMID- 27610712
TI - Non-steroid anti-inflammatory drugs for biliary colic.
AB - BACKGROUND: Cholelithiasis refers to the presence of gallstones, which are
concretions that form in the biliary tract, usually in the gallbladder.
Cholelithiasis is one of the most common surgical problems worldwide and is
particularly prevalent in most Western countries.Biliary colic is the term used
for gallbladder pain experienced by a person with gallstones and without overt
infection around the gallbladder. It is the most common manifestation of
cholelithiasis, observed in over one-third of people with gallstones over the
course of 10 or more years. Non-steroid anti-inflammatory drugs (NSAIDs) have
been widely used to relieve biliary colic pain, but their role needs further
elucidation. They may decrease the frequency of short-term complications, such as
mild form of acute cholecystitis, jaundice, cholangitis, and acute pancreatitis,
but they may also increase the occurrence of more severe and possibly life
threatening adverse events such as gastrointestinal bleeding, renal function
impairment, cardiovascular events, or milder events such as abdominal pain,
drowsiness, headache, dizziness, or cutaneous manifestations. OBJECTIVES: To
assess the benefits and harms of NSAIDs in people with biliary colic. SEARCH
METHODS: We searched the Cochrane Hepato-Biliary Controlled Trials Register,
Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library,
MEDLINE (Ovid SP), Embase (Ovid SP), Science Citation Index Expanded (Web of
Science), and ClinicalTrials.gov until July 2016. We applied no language
limitation. SELECTION CRITERIA: Randomised clinical trials recruiting
participants presenting with biliary colic and comparing NSAIDs versus no
intervention, placebo, or other drugs. DATA COLLECTION AND ANALYSIS: Two review
authors (MF and AC) independently identified trials for inclusion. We used risk
ratios (RR) to express intervention effect estimates, and we analysed the data
with both fixed-effect and random-effects model meta-analyses, depending on the
amount of heterogeneity. We controlled random errors with Trial Sequential
Analysis. We assessed the methodological quality of the evidence using GRADE
criteria. MAIN RESULTS: Twelve randomised clinical trials (RCTs) met our
predefined review protocol criteria for analysis. We found only one trial to be
at low risk of bias, considering the remaining trials to be at high risk of bias.
The risk of selection bias in nine studies was unclear due to poor reporting,
leading to uncertainty in the pooled effect estimates. Five trials compared
NSAIDs versus placebo, four trials compared NSAID versus opioids, and four trials
compared NSAID versus spasmolytic drugs (one of the 12 trials was a three-arm
study comparing NSAIDs versus both opioids and spasmolytic drugs). There were 828
randomised participants (minimum 30 and maximum 324 per trial), of whom 416
received NSAIDs and 412 received placebo, spasmolytic drugs, or opioids. Twenty
four per cent of the participants were males. The age of the participants in the
trials ranged from 18 to 86 years. All people were admitted to emergency
departments for acute biliary pain. There was no mortality. When compared with
placebo, NSAIDs obtained a significantly lower proportion of participants without
complete pain relief (RR 0.27, 95% confidence interval (CI) 0.19 to 0.40; I2 =
0%; 5 trials; moderate-quality evidence), which was confirmed by Trial Sequential
Analysis, but not regarding participants with complications (RR 0.66, 95% CI 0.38
to 1.15; I2 = 26%; 3 trials; very low-quality evidence). NSAIDs showed more pain
control than spasmolytic drugs (RR 0.51, 95% CI 0.37 to 0.71; I2 = 0%; 4 trials;
low-quality evidence), which was not confirmed by Trial Sequential Analysis, and
a significantly lower proportion of participants with complications (RR 0.27, 95%
CI 0.12 to 0.57; I2 = 0%; 2 trials; low-quality evidence), which was also not
confirmed by Trial Sequential Analysis. We found no difference in the proportions
of participants without complete pain relief when comparing NSAIDs versus opioids
(RR 0.98, 95% CI 0.47 to 2.07; I2 = 52%), suggesting moderate heterogeneity among
trials (4 trials; very low-quality evidence). Only one trial comparing NSAIDs
versus opioids reported results on complications, finding no significant
difference between treatments. None of the included trials reported severe
adverse events. Seven out of the 12 trials assessed non-severe adverse events: in
two out of the seven trials, adverse events were not observed, and minor events
were reported in the remaining five trials.In addition, we found one ongoing RCT
assessing the analgesic efficacy of intravenous ibuprofen in biliary colic.
AUTHORS' CONCLUSIONS: NSAIDs have been assessed in relatively few trials
including a limited number of participants for biliary colic, considering its
common occurrence. We found only one trial to be at low risk of bias. There was
no mortality. None of the included trials reported quality of life. The
generalisability of the review is low as most of the RCTs included neither
elderly people nor participants with comorbidities, who are more prone to
complications as compared to others with biliary colic.The beneficial effect of
NSAIDs compared with placebo on pain relief was confirmed when we applied Trial
Sequential Analysis.The quality of evidence according to GRADE criteria was
moderate for the comparison of NSAIDs versus placebo regarding the outcome lack
of pain relief and low or very low for the other outcomes and comparisons.We
found only one trial at low risk of bias, following the predefined 'Risk of bias'
domains. We found the risk of selection bias to be unclear in nine studies due to
poor reporting, leading to uncertainty in the pooled effect estimates.
PMID- 27610714
TI - Letters to the Editor.
PMID- 27610713
TI - Neutrophils in ulcerative colitis: a review of selected biomarkers and their
potential therapeutic implications.
AB - OBJECTIVES: This review article describes the role of neutrophils in mucosal
injury and the resulting crypt abscesses characteristic of ulcerative colitis. We
also review selected biomarkers for monitoring neutrophil presence and activity
in the mucosa as well as their potential as therapeutic targets. MATERIAL: We
have collated and selectively reviewed data on the most prominent well
established and emerging neutrophil-related biomarkers and potential therapeutic
targets (calprotectin, lactoferrin, CXCR1, CXCR2, MMP-9, NGAL, elafin, HNE,
pANCAs, MPO, CD16, CD177, CD64, HNPs, SLPI and PTX3) in ulcerative colitis.
RESULTS: Systemic and intestinal neutrophil activity increases substantially in
active ulcerative colitis, driving tissue damage and extra-intestinal
manifestations. Calprotectin is a robust neutrophil and disease biomarker, and a
few neutrophil-related targets are being clinically explored as therapeutic
targets. CONCLUSION: We propose that targeting neutrophils and their inflammatory
mediators per se is an opportunity that should be explored to identify new
effective medical therapies. The overall clinical goal for neutrophil-targeted
therapy will be to modulate, but not completely silence, neutrophil activity,
thereby abolishing the destructive inflammation with associated acute and chronic
tissue damage without compromising host-defense.
PMID- 27610715
TI - Review of Nonfoodborne Zoonotic and Potentially Zoonotic Poultry Diseases.
AB - Emerging and re-emerging diseases are continuously diagnosed in poultry species.
A few of these diseases are known to cross the species barrier, thus posing a
public health risk and an economic burden. We identified and synthesized global
evidence for poultry nonfoodborne zoonoses to better understand these diseases in
people who were exposed to different poultry-related characteristics (e.g.,
occupational or nonoccupational, operational types, poultry species, outbreak
conditions, health status of flocks). This review builds on current knowledge on
poultry zoonoses/potentially zoonotic agents transmitted via the nonfoodborne
route. It also identifies research gaps and potential intervention points within
the poultry industry to reduce zoonotic transmission by using various knowledge
synthesis tools such as systematic review (SR) and qualitative (descriptive) and
quantitative synthesis methods (i.e., meta-analysis). Overall, 1663 abstracts
were screened and 156 relevant articles were selected for further review. Full
articles (in English) were retrieved and critically appraised using routine SR
methods. In total, eight known zoonotic diseases were reviewed: avian influenza
(AI) virus (n = 85 articles), Newcastle disease virus (n = 8), West Nile virus
(WNV, n = 2), avian Chlamydia (n = 24), Erysipelothrix rhusiopathiae (n = 3),
methicillin-resistant Staphylococcus aureus (MRSA, n = 15), Ornithonyssus
sylvarium (n = 4), and Microsporum gallinae (n = 3). In addition, articles on
other viral poultry pathogens (n = 5) and poultry respiratory allergens derived
from mites and fungi (n = 7) were reviewed. The level of investigations (e.g.,
exposure history, risk factor, clinical disease in epidemiologically linked
poultry, molecular studies) to establish zoonotic linkages varied across disease
agents and across studies. Based on the multiple outcome measures captured in
this review, AI virus seems to be the poultry zoonotic pathogen that may have
considerable and significant public health consequences; however, epidemiologic
reports have only documented severe human cases clustered in Asia and not in
North America. In contrast, avian Chlamydia and MRSA reports clustered mainly in
Europe and less so in North America and other regions. Knowledge gaps in other
zoonoses or other agents were identified, including potential direct (i.e.,
nonmosquito-borne) transmission of WNV from flocks to poultry workers, the public
health and clinical significance of poultry-derived (livestock-associated) MRSA,
the zoonotic significance of other viruses, and the role of poultry allergens in
the pathophysiology of respiratory diseases of poultry workers. Across all
pathogens reviewed, the use of personal protective equipment was commonly cited
as the most important preventive measure to reduce the zoonotic spread of these
diseases and the use of biosecurity measures to reduce horizontal transmission in
flock populations. The studies also emphasized the need for flock monitoring and
an integrated approach to prevention (i.e., veterinary-public health coordination
with regard to diagnosis, and knowledge translation and education in the general
population) to reduce zoonotic transmission.
PMID- 27610716
TI - Hepatitis Virus Infections in Poultry.
AB - Viral hepatitis in poultry is a complex disease syndrome caused by several
viruses belonging to different families including avian hepatitis E virus (HEV),
duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck
hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis
virus (THV). While these hepatitis viruses share the same target organ, the
liver, they each possess unique clinical and biological features. In this
article, we aim to review the common and unique features of major poultry
hepatitis viruses in an effort to identify the knowledge gaps and aid the
prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus
B in the family Hepeviridae that naturally infects chickens and consists of three
distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly
syndrome or big liver and spleen disease in chickens, although the majority of
the infected birds are subclinical. Avihepadnaviruses in the family of
Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey
herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form
without clinical signs and rarely progressed to chronicity. The outcome for DHBV
infection varies by the host's ability to elicit an immune response and is dose
and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B
virus (HBV) infections and providing an excellent animal model for human HBV.
DHAV is a picornavirus that causes a highly contagious virus infection in ducks
with up to 100% flock mortality in ducklings under 6 wk of age, while older birds
remain unaffected. The high morbidity and mortality has an economic impact on
intensive duck production farming. Duck hepatitis virus Types 2 and 3 are
astroviruses in the family of Astroviridae with similarity phylogenetically to
turkey astroviruses, implicating the potential for cross-species infections
between strains. Duck astrovirus (DAstV) causes acute, fatal infections in
ducklings with a rapid decline within 1-2 hr and clinical and pathologic signs
virtually indistinguishable from DHAV. DAstV-1 has only been recognized in the
United Kingdom and recently in China, while DAstV-2 has been reported in ducks in
the United States. FAdV, the causative agent of inclusion body hepatitis, is a
Group I avian adenovirus in the genus Aviadenovirus. The affected birds have a
swollen, friable, and discolored liver, sometimes with necrotic or hemorrhagic
foci. Histologic lesions include multifocal necrosis of hepatocytes and acute
hepatitis with intranuclear inclusion bodies in the nuclei of the hepatocytes.
THV is a picornavirus that is likely the causative agent of turkey viral
hepatitis. Currently there are more questions than answers about THV, and the
pathogenesis and clinical impacts remain largely unknown. Future research in
viral hepatic diseases of poultry is warranted to develop specific diagnostic
assays, identify suitable cell culture systems for virus propagation, and develop
effective vaccines.
PMID- 27610717
TI - Morphometric Documentation of a High Prevalence of Left Ventricular Dilated
Cardiomyopathy in Both Clinically Normal and Cyanotic Mature Commercial Broiler
Breeder Roosters with Comparisons to Market-Age Broilers.
AB - Previous studies documented the common occurrence of transitory cyanosis and
echocardiographic aortic insufficiency in mature commercial broiler breeder
roosters. During further investigations, we observed a high prevalence of hearts
exhibiting extensive dilation of the left ventricle chamber compatible with
dilated left ventricular cardiomyopathy present in both cyanotic and normal
subpopulations. We conducted quantitative studies focused on documentation of
cardiac ventricle parameters by using simple gross morphometric methods performed
on formalin-fixed hearts obtained from both clinically normal roosters and those
exhibiting variable transitory cyanosis, echocardiographic aortic insufficiency,
or both. A high prevalence of often dramatic left ventricular dilation reflected
in enlarged left ventricular chamber areas and elevated left ventricle-to-total
ventricle area ratios was morphometrically documented. However, no statistically
significant differences in the occurrence of ventricular abnormalities were
observed between normal and cyanotic roosters. Age-associated changes were also
demonstrated by comparative morphometric studies on hearts from normal market-age
broilers (average age of 7 wk) and those of mature roosters (average age of 42
wk). Elevation in both left and right ventricular weight-to-total heart weight
ratios dramatically increased with aging. In addition, values (average +/- SD)
for the left ventricle chamber area-to-total ventricle area ratios increased from
3.2 +/- 2.0% in broilers up to 10.0 +/- 8.8% in roosters. None of the normal
broilers studied demonstrated left ventricular volume ratios above 10%, whereas
33% of the roosters had left ventricular volume ratios above 10%, including 13%
with ratios of 20% or higher. However, the left ventricle wall area-to-body
weight ratios were much closer for the two age groups (0.85 +/- 0.18 cm(2)/kg in
broilers and 0.79 +/- 0.13 cm(2)/kg in roosters). Also, the standard right
ventricle-to-total ventricle weight ratio (RV/TV) went from 0.18 +/- 0.04 in
broilers to 0.25 +/- 0.12 in roosters, whereas the left ventricle-to-total
ventricle weight ratios were similar for the two age groups (0.74 +/- 0.12 and
0.75 +/- 0.08 in broilers and roosters, respectively). Our results for RV/TV in
normal broilers were similar to the reported values for normal market-age
broilers. In contrast, 36% of the roosters had RV/TV above values reported for
broilers considered reflective of right ventricular hypertrophy due to pulmonary
hypertension, whereas 4% had values above the reported threshold for broilers
dying with ascites (ratios greater than 0.0249 and 0.299, respectively). However,
ascites was not observed for any of the roosters. Although essentially all
cardiac morphometric parameters demonstrated statistically significant
correlations with the age-class group comparisons, significance could not be
documented for comparisons between cardiomorphometrics and the subjective
occurrences of transitory cyanosis or echocardiographic aortic insufficiency.
PMID- 27610718
TI - Phylogeny and S1 Gene Variation of Infectious Bronchitis Virus Detected in
Broilers and Layers in Turkey.
AB - The avian coronavirus infectious bronchitis virus (AvCoV-IBV) is recognized as an
important global pathogen because new variants are a continuous threat to the
poultry industry worldwide. This study investigates the genetic origin and
diversity of AvCoV-IBV by analysis of the S1 sequence derived from 49 broiler
flocks and 14 layer flocks in different regions of Turkey. AvCoV-IBV RNA was
detected in 41 (83.6%) broiler flocks and nine (64.2%) of the layer flocks by
TaqMan real-time RT-PCR. In addition, AvCoV-IBV RNA was detected in the tracheas
27/30 (90%), lungs 31/49 (62.2%), caecal tonsils 7/22 (31.8%), and kidneys 4/49
(8.1%) of broiler flocks examined. Pathologic lesions, hemorrhages, and
mononuclear infiltrations were predominantly observed in tracheas and to a lesser
extent in the lungs and a few in kidneys. A phylogenetic tree based on partial S1
sequences of the detected AvCoV-IBVs (including isolates) revealed that 1)
viruses detected in five broiler flocks were similar to the IBV vaccines Ma5,
H120, M41; 2) viruses detected in 24 broiler flocks were similar to those
previously reported from Turkey and to Israel variant-2 strains; 3) viruses
detected in seven layer flocks were different from those found in any of the
broiler flocks but similar to viruses previously reported from Iran, India, and
China (similar to Israel variant-1 and 4/91 serotypes); and 4) that the AVCoV
IBV, Israeli variant-2 strain, found to be circulating in Turkey appears to be
undergoing molecular evolution. In conclusion, genetically different AvCoV-IBV
strains, including vaccine-like strains, based on their partial S1 sequence, are
circulating in broiler and layer chicken flocks in Turkey and the Israeli variant
2 strain is undergoing evolution.
PMID- 27610719
TI - Efficacy of Recombinant HVT-IBD Vaccines Administered to Broiler Chicks from a
Single Breeder Flock at 30 and 60 Weeks of Age.
AB - The efficacy of commercially available recombinant herpesvirus of turkeys
infectious bursal disease (rHVT-IBD) virus vaccines was studied in broiler
chickens derived from an IBDV-vaccinated breeder flock at 30 wk of age (Trial 1)
and 60 wk of age (Trial 2). In parallel, specific-pathogen-free (SPF) white
leghorn chickens were used to evaluate vaccine efficacy to control for the
effects of maternally derived antibodies (MDA) associated with the broiler
chickens. Broilers and SPF leghorns were vaccinated subcutaneously in the neck at
1 day of age with Vaxxitek(r) HVT+IBD or Vectormune(r) HVT-IBD vaccines and were
placed in isolators. On 10, 14, 18, 22, and 26 days postvaccination (DPV),
vaccinated and nonvaccinated broilers and SPF leghorns were bled prior to
challenge via the oral-nasal route with infectious bursal disease (IBD) reference
strains ST-C, Delaware variant E (Del E), or contemporary field isolates
DMV/5038/07 or FF6. Microscopic lesion assessment of the bursa was useful for
assessing IBDV challenge in both rHVT-IBD-vaccinated broiler and SPF leghorn
chickens. In general, rHVT-IBD vaccines induced greater protection as the time
between vaccination and challenge increased. Based on incidence of microscopic
lesions (IML) of bursa tissue, Vaxxitek HVT+IBD vaccination of SPF leghorns
induced protection by 18 DPV and continued to protect 22 DPV and 26 DPV in Trials
1 and 2. Vectormune HVT-IBD vaccine induced protection of SPF leghorns by 18 or
22 DPV in Trial 1, depending upon the IBDV challenge strain. However, the onset
of protection was delayed until 22 or 26 DPV in Trial 2. With either commercial
vaccine, rHVT-IBD vaccination of broiler chickens was not as effective as was
observed in SPF leghorns, based on IML of bursa tissue. However, Vaxxitek HVT+IBD
vaccination protected broilers following challenge with ST-C in both Trial 1 (30
wk-old breeder progeny) and Trial 2 (60-wk-old breeder progeny). Partial
protection against FF6 (Trial 1) and DMV/5038/07 (Trial 2) challenges was
observed. Vectormune HVT-IBD vaccination protected broilers vs. FF6 challenge in
Trial 1. In Trial 2, the vaccine did not offer protection on the basis of IML of
bursa tissue. The results indicate that 1) bursa/body weight ratios were not
consistently useful as a tool for assessing IBDV challenge in broiler chickens
with anti-IBDV MDA compared to assessment by IML of bursa tissue, though were
useful for assessing protection in SPF leghorns; and 2) both vaccines may offer
some protection to older broilers; however, a window of susceptibility exists
between the waning of MDA and the development of vaccine-induced antibodies. The
SPF studies showed that some vaccinated chickens were not protected from an IBDV
challenge earlier than 14 DPV while broiler studies showed that MDA was not fully
protective beyond 10 DPV. Because these vaccines did not protect chickens from an
IBDV challenge during this window of susceptibility, our data show that breeder
vaccination programs for IBDV must aim to maximize anti-IBDV MDA in progeny to
protect against early IBDV challenge.
PMID- 27610721
TI - Development and Evaluation of the Protective Efficacy of Novel Marek's Disease
Virus Rispens Vector Vaccines Against Infectious Bursal Disease.
AB - Infectious bursal disease (IBD) is a major disease affecting the poultry industry
and is caused by infection with IBD virus (IBDV). To develop a novel vaccine to
prevent IBD in chickens, recombinant Marek's disease virus Rispens viruses
carrying the VP2 gene of IBDV driven by five different promoters (Rispens/IBD)
were constructed using homologous recombination and a bacterial artificial
chromosome (BAC). Rispens/IBD driven by the chicken beta-actin (Bac) promoter
(Rispens/Bac-IBD), Rous sarcoma virus promoter, or simian virus 40 promoter were
administered to 1-day-old SPF chicks, and the protective efficacy against IBDV
was evaluated by challenging chicks with virulent IBDV. As a result, Rispens/Bac
IBD showed the best protection (87%). Next, we constructed the virus driven by
the Bac-derived Coa5 promoter (Rispens/Coa5-IBD) for a secondary in vivo trial
using commercial layer chickens since Rispens/Bac-IBD was thought to be
genetically unstable. Rispens/Coa5-IBD showed stability in vitro and exhibited
better antibody production and protection during challenge against virulent IBDV
at both 5 (95%) and 7 wk of age (91%) compared with that of Rispens/Bac-IBD (90%
at 5 wk of age and 84% at 7 wk of age). Thus, Rispens/Coa5-IBD may be a novel
promising vaccine against IBD and virulent Marek's disease.
PMID- 27610720
TI - Virucidal Properties of Bioceramic Derived from Chicken Feces pH 13 and its
Stability in Harsh Environments.
AB - Bioceramic derived from chicken feces (BCX) is a material produced by a sintering
process for the purpose of use in animal farms to control livestock infectious
diseases. In the present study, BCX at pH 13 was evaluated for the durability of
its virucidal activity in simulated field conditions. First it was shown that BCX
had activity toward Newcastle disease virus, infectious bursal disease virus, and
goose parvovirus within 3 min and toward avian influenza virus (AIV) within 1 hr.
BCX was further tested by keeping it under simulated harsh environmental
conditions with sunlight for several weeks as well as by repeatedly soaking it
with water and drying under sunlight many times. After sampling every 2
consecutive weeks and every 2 (of 9) consecutive resuspensions, BCX was evaluated
for its efficacy against AIV. Evaluation under the harsh conditions illustrated
that BCX could retain its satisfactory efficacy toward AIV throughout 7 wk and
through 9 resuspensions. It is hence concluded that BCX is an excellent material
for applying in livestock farming as a trapping disinfectant, due to its efficacy
to inactivate various viruses, and that this efficacy is prolonged even under
harsh environmental conditions.
PMID- 27610722
TI - The Enrichment of Histomonas meleagridis and Its Pathogen-Specific Protein
Analysis: A First Step to Shed Light on Its Virulence.
AB - Since the discovery of Histomonas meleagridis in 1893, the necessity of isolating
pure H. meleagridis has been highlighted over the years in the battle against
histomonosis. Insights into the molecular characteristics of this protozoon open
possibilities to proper treatment. Axenization of H. meleagridis in vitro
cultures cocultured with bacteria has been unsuccessful. Numerous unsuccessful
attempts at culturing H. meleagridis axenically have reinforced the assumption
that the protozoa had an obligate relationship with certain bacteria originating
from the host ceca. Within these perspectives, we enriched H. meleagridis cells
from a mono-eukaryotic culture copropagated with host cecal bacteria by flow
cytometry. The enrichment of histomonads was confirmed through transmission
electron microscopy and two-dimensional gel electrophoresis. For the first time
several protein spots were successfully identified. The majority of spots were
annotated as cytoskeletal proteins. Actin microfilaments are known to be a key
player in cell spreading, cell adhesion, phagocytosis, signal transduction, and
several other processes. Together with the identification of superoxide
dismutase, the information generated from protein analysis of H. meleagridis may
serve as a very first step toward understanding its pathogenesis and virulence.
PMID- 27610723
TI - Investigation into the Airborne Dissemination of H5N2 Highly Pathogenic Avian
Influenza Virus During the 2015 Spring Outbreaks in the Midwestern United States.
AB - We investigated the plausibility of aerosol transmission of H5N2 highly
pathogenic avian influenza (HPAI) virus during the 2015 spring outbreaks that
occurred in the U.S. midwest. Air samples were collected inside and outside of
infected turkey and layer facilities. Samples were tested to assess HPAI virus
concentration (RNA copies/m(3) of air), virus viability, and virus distribution
by particle size. HPAI virus RNA was detected inside and up to 1000 m from
infected facilities. HPAI virus was isolated from air samples collected inside,
immediately outside, up to 70 m from infected facilities, and in aerosol
particles larger than 2.1 MUm. Direct exposure to exhausted aerosols proved to be
a significant source of environmental contamination. These findings demonstrate
HPAI virus aerosolization from infected flocks, and that both the transport of
infectious aerosolized particles and the deposition of particles on surfaces
around infected premises represent a potential risk for the spread of HPAI.
PMID- 27610724
TI - Mortality and Disease in Wild Turkeys ( Meleagris gallopavo silvestris) in
Ontario, Canada, from 1992 to 2014: A Retrospective Review.
AB - Wild turkeys ( Meleagris gallopavo silvestris) were extirpated from Ontario,
Canada, in the early 1900s due to unregulated over-hunting and habitat loss.
Despite a successful reintroduction program and strong population numbers,
information regarding the health of wild turkeys in Ontario is scarce. A 22-yr
(1992-2014) retrospective study was performed to evaluate diagnostic data,
including the cause(s) and contributors to death, in wild turkeys submitted to
the Ontario-Nunavut node of the Canadian Wildlife Health Cooperative (n = 56).
Noninfectious diagnostic findings (39/56; 69.6%) were more common than
infectious, with emaciation recognized most frequently (n = 19; 33.9%) followed
by trauma (n = 11, 19.6%). The majority of deaths due to emaciation occurred in
winter and spring (17/18; 94.4%), which is consistent with lack of access to or
availability of food resources. Morbidity and mortality due to infectious
diseases was diagnosed in 16 (28.6%) wild turkeys. Avian poxvirus was the most
common infectious cause of disease (n = 7; 12.5%), followed by bacterial
infections (n = 5; 8.9%), the most common of which was Pasteurella multocida .
Zinc phosphide toxicosis (n = 7; 12.5%) occurred in two incidents involving
multiple birds. This study aims to provide baseline data that can be used for
reference and comparison in future wild turkey disease surveillance and
population monitoring studies.
PMID- 27610725
TI - The Fimbrial Protein is a Virulence Factor and Potential Vaccine Antigen of
Avibacterium paragallinarum.
AB - Fimbriae are recognized as virulence factors and potential vaccine antigens of
several pathogenic bacteria, but the function of the fimbriae from Avibacterium
paragallinarum is not well known. In this study, a gene encoding the fimbrial
protein FlfA was identified in A. paragallinarum . Sequencing analysis of the
putative promoter region of flfA suggests that flfA expression in A.
paragallinarum might be controlled by phase variation. The flfA gene from A.
paragallinarum was expressed as a recombinant protein (r-FlfA) in Escherichia
coli . Immunization with r-FlfA conferred chickens protection against challenge
infection with A. paragallinarum . Virulence assays showed that the flfA
deficient mutants of A. paragallinarum were less virulent than their parental
wild-type strains. These results indicated that the fimbrial protein FlfA is a
virulence factor and potential vaccine antigen from A. paragallinarum .
PMID- 27610726
TI - Gammacoronavirus and Deltacoronavirus in Quail.
AB - This paper expands on a previous report about coronaviruses in quail. After
surveillance carried out in 2009 and 2010, some farmers started vaccinating quail
with the Massachusetts avian infectious bronchitis virus serotype. The samples
for this study were collected in 2013 from Sao Paulo state in southeastern
Brazil. Pools of trachea, lungs, reproductive tract, kidneys, and enteric
contents from quail and laying hens kept in the same farms and from quail-only
farms as well as from both healthy birds and those showing infectious bronchitis
like symptoms were sampled in this study. The samples were screened using nested
RT-PCR targeting the 3'-untranslated region of the Gammacoronavirus genus. Based
on the DNA sequence for the RNA-dependent RNA polymerase (RdRp) gene, the strains
isolated from quail clustered within either the Gammacoronavirus or
Deltacoronavirus genus, and sequences from both genera were found in one quail
sample. The phylogeny based on the partial S1 subunit sequence showed that the
gammacoronaviruses detected in quail and layers belonged to the Brazil type.
These results suggest that quail are susceptible to Gammacoronavirus and
Deltacoronavirus viruses and indicate that the Massachusetts vaccination was not
controlling IBV in quail or chickens.
PMID- 27610727
TI - Efficacy of Various HVT Vaccines (Conventional and Recombinant) Against Marek's
Disease in Broiler Chickens: Effect of Dose and Age of Vaccination.
AB - Herpesvirus of turkeys (HVT) has been successfully used as a Marek's disease (MD)
vaccine for more than 40 yr. Either alone (broiler chickens) or in combination
with vaccines of other serotypes (broilers, broiler breeders, and layers), HVT is
used worldwide. In recent years, several vector vaccines based on HVT (rHVT) have
been developed. At present, there are both conventional HVT and rHVTs in the
market, and it is unknown if all of them confer the same level of protection
against MD. The objective of this study was to further characterize the
protection conferred by two conventional HVTs (HVT-A and HVT-B) and three
recombinant HVTs (rHVT-B, rHVT-C, and rHVT-D) against MD in broiler chickens. In
a first study we evaluated the efficacy of two conventional HVTs (HVT-A and HVT
B) administered at different doses (475, 1500, and 4000 PFU) at day of age on the
ability to protect against an early challenge with very virulent plus strain 645.
In a second experiment we evaluated the protection ability of several HVTs (both
conventional and recombinant) when administered in ovo at a dose of 1500 PFU
using the same challenge model. Our results show that each HVT product is unique,
regardless of being conventional or recombinant, in their ability to protect
against MD and might require different PFUs to achieve its maximum efficacy. In
Experiment 1, HVT-A at 4000 PFU conferred higher protection (protection index
[PI] = 63) than any of the other vaccine protocols (PI ranging from 36 to 47). In
Experiment 2, significant differences were found among vaccine protocols with PI
varying from 66 (HVT-A) to 15 (rHVT-D). Our results show that each HVT is unique
and age at vaccination and vaccine dose greatly affected vaccine efficacy.
Furthermore, they highlight the need of following manufacturer's recommendations.
PMID- 27610728
TI - Serotyping, Genotyping, and Antimicrobial Susceptibility of Ornithobacterium
rhinotracheale Isolates from Mexico.
AB - The bacterium Ornithobacterium rhinotracheale is associated with respiratory
disease and septicemia in poultry. In this study, 9 reference strains and a total
of 23 isolates of O. rhinotracheale from respiratory diseased poultry from Mexico
were serotyped and genotyped. Furthermore, the antimicrobial susceptibility of
isolates and reference strains of O. rhinotracheale were determined. All isolates
belong to serotype A and showed a clonal relationship. All reference strains and
isolates were resistant to colistin, fosfomycin, gentamicin, kanamycin,
streptomycin, and trimethoprim-sulfamethoxazole. These results should eventually
be helpful in planning strategies for the control of O. rhinotracheale infections
in poultry in Mexico.
PMID- 27610729
TI - Antimicrobial Sensitivity of Avibacterium paragallinarum Isolates from Four Latin
American Countries.
AB - The antimicrobial sensitivity of 11 reference strains and 66 Avibacterium
paragallinarum isolates from four Latin American countries was investigated. All
11 reference strains were sensitive to amoxicillin-clavulanic acid, ampicillin,
fosfomycin, gentamicin, kanamycin, neomycin, penicillin, tetracycline, and
trimethoprim-sulfamethoxazole. The 11 reference strains were all resistant to
lincomycin. All isolates (100%) from Mexico, Panama, and Peru were sensitive to
amoxicillin-clavulanic acid, ampicillin, and fosfomycin. The Ecuadorian isolates
showed some level of resistance to all 16 agents tested. The Ecuadorian isolates
were significantly more sensitive to erythromycin, lincomycin, and streptomycin,
and significantly more resistant to gentamicin, kanamycin, penicillin, and
tetracycline, than the Mexican isolates. A total of 57.5% (38/66) of tested
isolates were multi-drug resistant (MDR), with 16 MDR patterns detected in 88.4%
(23/26) of the antimicrobial-resistant isolates from Ecuador, and 8 MDR patterns
detected in 42.8% (15/35) of the antimicrobial-resistant isolates from Mexico. In
conclusion, the variation in antimicrobial sensitivity patterns between isolates
from Ecuador and Mexico emphasizes the importance of active, ongoing monitoring
of A. paragallinarum isolates.
PMID- 27610730
TI - Outbreak of Avian Tuberculosis in Commercial Domestic Pekin Ducks ( Anas
platyrhynchos domestica).
AB - Avian tuberculosis is a contagious disease affecting various domestic and wild
bird species, and is caused by Mycobacterium avium . It is reported extremely
rarely in commercial poultry flocks and has not been reported in commercial
domestic ducks to date, with domestic ducks reported to be moderately resistant
to M. avium infection. Here, we report the outbreak of avian tuberculosis in
commercial Pekin duck ( Anas platyrhynchos domestica) flocks. Postmortem and
histopathologic findings included nodules presenting in the visceral organs of
ducks, and granulomas with central caseous necrosis surrounded by infiltrating
lymphocytes. The M. avium pathogen was isolated and further identified by Ziehl
Neelsen staining and PCR based on insert sequence IS901 and the 16S rRNA gene. We
highlight that avian tuberculosis not only has economic significance for the duck
industry, but also presents a potential zoonotic hazard to humans.
PMID- 27610731
TI - Turkey Astrovirus Type 1 (TAstV-1) and Chicken Astrovirus (CAstV) Detection in
Brazilian Chicken Flocks.
AB - Astrovirus is a common cause of enteritis in humans and domestic animals. Here we
report the detection of turkey astrovirus type 1 (TAstV-1) and chicken astrovirus
(CAstV) in avian farms. Sixty fecal sample pools (five or six birds of the same
flock), from chickens without apparent clinical symptoms of enteric disease from
farms located in six Brazilian states, were screened by an ORF1b PCR, followed by
nucleotide sequencing of amplified products and phylogenetic analysis. Six
samples tested positive for TAstV-1 and two for CAstV. One positive sample of
each detected virus (TAstV-1 and CAstV) had the complete ORF2 sequenced. Data for
the ORF2 sequence indicate that Brazilian TAstV-1 was divergent from TAstV-1
(United States), previously described infecting turkeys, and Brazilian CAstV
clustered together with the U.K. group, subgroup B-II, associated with enteritis
and growth retardation in chicks. This study provides updated information about
CAstV and the first report of detection of TAstV-1 in Brazilian chickens,
supporting the diagnostic of enteritis and epidemiologic surveillance in poultry
health.
PMID- 27610732
TI - Highly Pathogenic Eurasian H5N8 Avian Influenza Outbreaks in Two Commercial
Poultry Flocks in California.
AB - In January 2015, a highly pathogenic Eurasian lineage H5N8 avian influenza (AI)
virus (AIV) was detected in a commercial meat turkey flock in Stanislaus County,
CA. Approximately 3 wk later, a similar case was diagnosed in commercial brown
layers from a different company located in Kings County, CA. Five 14-wk-old
turkey hens were submitted to the California Animal Health and Food Safety
Laboratory System (CAHFS), Turlock, and eleven 12-wk-old chickens were submitted
to CAHFS, Tulare laboratory due to an acute increase in flock mortality. Gross
lesions included enlarged and mottled pale spleens and pancreas in turkeys and
chickens. Histologically, the major lesions observed in turkeys and chickens were
splenitis, pancreatitis, encephalitis, and pneumonia. In both cases, diagnosis
was based on real-time reverse transcriptase PCR (RRT-PCR), sequencing, and virus
isolation from oropharyngeal and cloacal swabs. Confirmatory diagnosis and AIV
characterization was done at the National Veterinary Services Laboratory, Ames,
IA. The sequence of the AIV from both cases was 99% identical to an H5N8 AI virus
(A/gyrfalcon/Washington/41088-6/2014) isolated from a captive gyrfalcon (Falco
rusticolus) from Washington State in December 2014. Immunohistochemistry (IHC)
performed on various tissues from both cases indicated a widespread AIV tissue
distribution. Except for minor variations, the tissue distribution of the AI
antigen was similar in the chickens and turkeys. There was positive IHC staining
in the brain, spleen, pancreas, larynx, trachea, and lungs in both chickens and
turkeys. Hearts, ovaries, and air sacs from the turkeys were also positive for
the AI antigen. The liver sections from the chickens had occasional AI-positive
staining in mononuclear cells, but the IHC on liver sections from the turkeys
were negative. The bursa of Fabricius, small intestine, kidney, and skeletal
muscle sections were negative for the AI antigen in both chickens and turkeys.
PMID- 27610733
TI - Squamous Cell Carcinoma of the Oropharynx and Esophagus with Pulmonary Metastasis
in a Backyard Laying Hen.
AB - A backyard laying hen exhibiting muscular atrophy, dyspnea, and absence of egg
production was analyzed for diagnostic insights. Gross findings revealed the
presence of a large ulcerated mass with irregular edges involving the caudal part
of the oropharynx and the cranial part of the esophagus, occluding the lumen of
the esophagus and compressing the trachea. Small nodular lesions were detected
also in the lungs. Histologically, both esophageal and pulmonary masses were
characterized by nests of pleomorphic epithelial cells with squamous
differentiation. The diagnosis was of squamous cell carcinoma of the esophagus
with the uncommon feature of pulmonary metastasis.
PMID- 27610734
TI - Natural Infection with Avian Hepatitis E Virus and Marek's Disease Virus in Brown
Layer Chickens in China.
AB - In the present study, avian hepatitis E virus (HEV) and serotype-1 strains of
Marek's disease virus (MDV-1) were detected from a flock of 27-wk-old brown layer
hens in China, accompanied by an average daily mortality of 0.44%. Postmortem
examination of 25 sick hens and five apparently healthy hens selected randomly
from the flock showed significant pathologic changes consistent with hepatitis
splenomegaly syndrome (HSS), including hepatomegaly, peritoneal fluid, and
hepatic subcapsular hemorrhages. Microscopic examination of these livers showed
multifocal necrotizing hepatitis and mild lymphocytic infiltration. These liver
samples were investigated for HEV by reverse-transcription PCR. The overall
detection rate of HEV RNA in samples of sick chickens was about 56% (14/25),
while in samples from apparently healthy hens, it was 80% (4/5). Sequencing
analysis of three 242-base-pair fragments of the helicase gene revealed 95.5% to
97.9% nucleotide identity compared with published avian HEV genotype 3, whereas
identities demonstrated only 77.3% to 86.0% similarity when compared with
genotypes 1, 2, and 4. Unexpectedly, the MDV meq gene was detected in livers from
both apparently healthy chickens (2/5) and sick chickens (12/25) by PCR analysis.
The meq gene (396 base pairs) was determined to belong to MDV-1 by further
sequencing. The co-infection rate of avian HEV and MDV in this flock was 30%
(9/30). This is the first report of dual infection of a nonenvelope RNA virus
(HEV) with a herpesvirus (MDV) in chickens in China.
PMID- 27610736
TI - Erratum.
PMID- 27610735
TI - Concurrent Fowlpox and Candidiasis Diseases in Backyard Chickens with Unusual Pox
Lesions in the Bursa of Fabricius.
AB - Concurrent fowlpox and candidiasis diseases occurred in a backyard chicken flock.
Four deceased chickens (one Nagoya breed and three white silkie chickens) were
examined for diagnosis. At necropsy, white curd-like plaques were observed in the
crop. Fungal elements that stained positive for Candida albicans with
immunohistochemistry were distributed throughout the tongue, choanal mucosa,
esophagus, and crop. Typical fowlpox lesions, composed of proliferating
epithelial cells with ballooning degeneration and viral intracytoplasmic
inclusions, were observed in the conjunctiva, nasal mucosa, and skin around the
cloaca. Interestingly, hyperplastic interfollicular epithelium with rare virus
inclusions was observed in the bursa of Fabricius (BF). Some bursal follicles
were replaced by proliferating epithelial cells. These proliferating cells
immunohistochemically stained positive for cytokeratin. PCR and subsequent
genetic sequencing detected the C. albicans gene in the crop, and fowlpox virus
genes in the BF. These results indicate that this outbreak was a rare
presentation of fowlpox in spontaneously infected chickens, with unusual pox
lesions in the BF.
PMID- 27610738
TI - Cover Advertisements.
AB - Please see the PDF version of these advertisements.
PMID- 27610741
TI - Community-Based Providers' Selection of Practices for Children and Adolescents
With Comorbid Mental Health Problems.
AB - The goal of this study is to explore providers' patterns of implementation by
investigating how community mental health providers selected therapy practice
modules from a flexible, modular evidence-based treatment working with youths
with comorbid mental health problems. Data were obtained from 57 youths, 5-15
years old, presenting with anxiety, depressive, and/or conduct problems and their
27 providers during their participation in an effectiveness trial involving a
modular evidence-based treatment. Although all youths evidenced clinically
elevated symptomatology in at least two problem areas, providers targeted youths'
comorbid problems with only about half of their study cases. Practice modules
indicated for youths' comorbid problems were typically used less frequently and
with less depth relative to practice modules indicated for youths' principal
clinical problem and were often transdiagnostic in nature (i.e., designed to
target more than one problem area). To determine whether providers' decisions to
target youths' comorbid problems were systematic, multilevel, logistic regression
analyses were conducted and revealed that youths' pretreatment characteristics
and time in therapy influenced providers' patterns of module selection. Providers
tend to use, but not exploit, the flexibility allowed by modular EBTs and to
focus treatment on youths' principal presenting problem. In addition, providers
appear to make these practice choices in a systematic and rational manner, and
whether and which choices are associated with improved outcomes is an important
area of future study.
PMID- 27610743
TI - High-Fat Diet Induces Distinct Metabolic Response in Interleukin-6 and Tumor
Necrosis Factor-alpha Knockout Mice.
AB - Studies suggest interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
may be beneficial in obesity-related disorders with inconsistent results. This
study was designed to investigate and compare their pathophysiological roles in
lipid metabolism with gene knockout approach. Male wild-type (WT), IL-6 knockout
(IL-6-/-), and TNF-alpha knockout (TNF-alpha-/-) mice were maintained on either a
chow diet or a high-fat diet (HFD) for 12 weeks. Indices of lipid metabolism in
blood, adipose, and liver were determined. Our data showed that IL-6-/- and TNF
alpha-/- mice were more pronounced in body weight gains, hypercholesterolemia,
fasting and post-load hyperglycemia on a chow diet or a HFD compared with WT
mice. In WT mice feeding on a HFD, lipolysis and glyceroneogenesis were enhanced,
lipogenesis was inhibited in adipose tissue; lipogenesis was increased in liver
tissue. IL-6-/- mice on a chow diet or a HFD showed similar metabolic phenotypes
as WT mice on a HFD, since those mice had similar expression profiles of lipid
related genes in adipose tissue and liver. However, TNF-alpha-/- mice were
different. Therefore, IL-6-/- and TNF-alpha-/- mice showed different hepatic
triglyceride infiltration in response to different diets. Our study suggests that
complete blockage of IL-6 and TNF-alpha is unbeneficial in obesity and obesity
related metabolic disorders in mice.
PMID- 27610742
TI - Precise quantification of mixtures of bispecific IgG produced in single host
cells by liquid chromatography-Orbitrap high-resolution mass spectrometry.
AB - Bispecific IgG are heterotetramers comprising 2 pairs of heavy and light chains.
Co-expression of the 4 component chains in a single host cell typically yields
the desired bispecific IgG plus up to 9 additional incorrect chain pairings.
Several protein engineering strategies have been reported to facilitate the
heterodimerization of antibody heavy chains or cognate pairing of antibody heavy
and light chains. These technologies have been used to direct the efficient
assembly of bispecific IgG in single host cells and minimize unwanted chain
pairings. When purifying bispecific IgGs, the identification and quantification
of low levels of closely related IgG contaminants are substantial analytical
challenges. Here we have developed a robust high-throughput method for
quantitative analysis of bispecific IgG preparations using novel online liquid
chromatography in conjunction with an extended mass range Orbitrap-based high
resolution mass spectrometer. A mathematical method was developed to estimate the
yields of the 2 isobaric species, namely the desired bispecific IgG and the light
chain-scrambled IgG. The analytical methods described herein are anticipated to
be broadly applicable to the development of bispecific IgG as drugs and
potentially to other complex next-generation biotherapeutics.
PMID- 27610744
TI - Biomonitoring of heavy metals contamination by mosses and lichens around Slovinky
tailing pond (Slovakia).
AB - Three moss (Pleurozium spp., Polytrichum spp., and Rhytidiadelphus spp.) and two
lichen (Hypogymnia physodes and Pseudevernia furfuracea) taxons covered in the
bags were used to monitor air quality. Bags were exposed at the different
distances from the tailing pond because of insufficient security and source of
heavy metal pollution. Moss/lichen bags were exposed for six weeks at 0-, 50-,
100-, 150- and 200-m distances from Slovinky tailing pond, in the main wind
direction (down the valley). Accumulation ability of heavy metals expressed by
relative accumulation factor (RAF) increases in the order of Polytrichum spp.2 GeV. If, instead, the RH
neutrinos have not thermalized, leptogenesis from these decays is enhanced
further and can be easily successful, even at lower scales. This Higgs-decay
leptogenesis new mechanism works without requiring an interplay of flavor effects
and/or cancellations of large Yukawa couplings in the neutrino mass matrix. Last
but not least, such a scenario turns out to be testable, from direct production
of the RH neutrino(s).
PMID- 27610846
TI - Supersymmetric Explanation of CP Violation in K->pipi Decays.
AB - Recent progress in the determination of hadronic matrix elements has revealed a
tension between the measured value of epsilon_{K}^{'}/epsilon_{K}, which
quantifies direct CP violation in K->pipi decays, and the standard-model
prediction. The well-understood indirect CP violation encoded in the quantity
epsilon_{K} typically precludes large new-physics contributions to
epsilon_{K}^{'}/epsilon_{K} and challenges such an explanation of the
discrepancy. We show that it is possible to cure the epsilon_{K}^{'}/epsilon_{K}
anomaly in the minimal supersymmetric standard model with squark masses above 3
TeV without overshooting epsilon_{K}. This solution exploits two features of
supersymmetry: the possibility of large isospin-breaking contributions (enhancing
epsilon_{K}^{'}) and the Majorana nature of gluinos (permitting a suppression of
epsilon_{K}). Our solution involves no fine-tuning of CP phases or other
parameters.
PMID- 27610847
TI - Decays of the Three Top Contributors to the Reactor nu[over -]_{e} High-Energy
Spectrum, ^{92}Rb, ^{96gs}Y, and ^{142}Cs, Studied with Total Absorption
Spectroscopy.
AB - We report total absorption spectroscopy measurements of ^{92}Rb, ^{96gs}Y, and
^{142}Cs beta decays, which are the most important contributors to the high
energy nu[over -]_{e} spectral shape in nuclear reactors. These three beta decays
contribute 43% of the nu[over -]_{e} flux near 5.5 MeV emitted by nuclear
reactors. This nu[over -]_{e} energy is particularly interesting due to spectral
features recently observed in several experiments including the Daya Bay, Double
Chooz, and RENO Collaborations. Measurements were conducted at Oak Ridge National
Laboratory by means of proton-induced fission of ^{238}U with on-line mass
separation of fission fragments and the Modular Total Absorption Spectrometer. We
observe a beta-decay pattern that is similar to recent measurements of ^{92}Rb,
with a ground-state to ground-state beta feeding of 91(3)%. We verify the
^{96gs}Y ground-state to ground-state beta feeding of 95.5(20)%. Our measurements
substantially modify the beta-decay feedings of ^{142}Cs, reducing the beta
feeding to ^{142}Ba states below 2 MeV by 32% when compared with the latest
evaluations. Our results increase the discrepancy between the observed and the
expected reactor nu[over -]_{e} flux between 5 and 7 MeV, the maximum excess
increases from ~10% to ~12%.
PMID- 27610849
TI - Attosecond Delays in Molecular Photoionization.
AB - We report measurements of energy-dependent photoionization delays between the two
outermost valence shells of N_{2}O and H_{2}O. The combination of single-shot
signal referencing with the use of different metal foils to filter the attosecond
pulse train enables us to extract delays from congested spectra. Remarkably large
delays up to 160 as are observed in N_{2}O, whereas the delays in H_{2}O are all
smaller than 50 as in the photon-energy range of 20-40 eV. These results are
interpreted by developing a theory of molecular photoionization delays. The long
delays measured in N_{2}O are shown to reflect the population of molecular shape
resonances that trap the photoelectron for a duration of up to ~110 as. The
unstructured continua of H_{2}O result in much smaller delays at the same photon
energies. Our experimental and theoretical methods make the study of molecular
attosecond photoionization dynamics accessible.
PMID- 27610848
TI - Evidence for Gamow-Teller Decay of ^{78}Ni Core from Beta-Delayed Neutron
Emission Studies.
AB - The beta-delayed neutron emission of ^{83,84}Ga isotopes was studied using the
neutron time-of-flight technique. The measured neutron energy spectra showed
emission from states at excitation energies high above the neutron separation
energy and previously not observed in the beta decay of midmass nuclei. The large
decay strength deduced from the observed intense neutron emission is a signature
of Gamow-Teller transformation. This observation was interpreted as evidence for
allowed beta decay to ^{78}Ni core-excited states in ^{83,84}Ge favored by shell
effects. We developed shell model calculations in the proton fpg_{9/2} and
neutron extended fpg_{9/2}+d_{5/2} valence space using realistic interactions
that were used to understand measured beta-decay lifetimes. We conclude that
enhanced, concentrated beta-decay strength for neutron-unbound states may be
common for very neutron-rich nuclei. This leads to intense beta-delayed high
energy neutron and strong multineutron emission probabilities that in turn affect
astrophysical nucleosynthesis models.
PMID- 27610850
TI - Core Ionization Initiates Subfemtosecond Charge Migration in the Valence Shell of
Molecules.
AB - After the ionization of a valence electron, the created hole can migrate
ultrafast from one end of the molecule to another. Because of the advent of
attosecond pulse techniques, the measuring and understanding of charge migration
has become a central topic in attosecond science. Here, we pose the hitherto
unconsidered question whether ionizing a core electron will also lead to charge
migration. It is found that the created hole in the core stays put, but in
response to this hole interesting electron dynamics takes place which can lead to
intense charge migration in the valence shell. This migration is typically faster
than that after the ionization of a valence electron and transpires on a shorter
time scale than the natural decay of the core hole by the Auger process, making
the subject very challenging to attosecond science.
PMID- 27610851
TI - Enhancing High-Order Harmonic Generation in Light Molecules by Using Chirped
Pulses.
AB - One of the current challenges in high-harmonic generation is to extend the
harmonic cutoff to increasingly high energies while maintaining or even
increasing the efficiency of the high-harmonic emission. Here we show that the
combined effect of down-chirped pulses and nuclear dynamics in light molecules
allows one to achieve this goal, provided that long enough IR pulses are used to
allow the nuclei to move well outside the Franck-Condon region. We also show
that, by varying the duration of the chirped pulse or by performing isotopic
substitution while keeping the pulse duration constant, one can control the
extension of the harmonic plateau.
PMID- 27610852
TI - Extreme-Ultraviolet-Initated High-Order Harmonic Generation: Driving Inner
Valence Electrons Using Below-Threshold-Energy Extreme-Ultraviolet Light.
AB - We propose a novel scheme for resolving the contribution of inner- and outer
valence electrons in extreme-ultraviolet (XUV)-initiated high-harmonic generation
in neon. By probing the atom with a low-energy (below the 2s ionization
threshold) ultrashort XUV pulse, the 2p electron is steered away from the core,
while the 2s electron is enabled to describe recollision trajectories. By
selectively suppressing the 2p recollision trajectories, we can resolve the
contribution of the 2s electron to the high-harmonic spectrum. We apply the
classical trajectory model to account for the contribution of the 2s electron,
which allows for an intuitive understanding of the process.
PMID- 27610839
TI - Antiproton Flux, Antiproton-to-Proton Flux Ratio, and Properties of Elementary
Particle Fluxes in Primary Cosmic Rays Measured with the Alpha Magnetic
Spectrometer on the International Space Station.
AB - A precision measurement by AMS of the antiproton flux and the antiproton-to
proton flux ratio in primary cosmic rays in the absolute rigidity range from 1 to
450 GV is presented based on 3.49*10^{5} antiproton events and 2.42*10^{9} proton
events. The fluxes and flux ratios of charged elementary particles in cosmic rays
are also presented. In the absolute rigidity range ~60 to ~500 GV, the
antiproton p[over -], proton p, and positron e^{+} fluxes are found to have
nearly identical rigidity dependence and the electron e^{-} flux exhibits a
different rigidity dependence. Below 60 GV, the (p[over -]/p), (p[over -]/e^{+}),
and (p/e^{+}) flux ratios each reaches a maximum. From ~60 to ~500 GV, the
(p[over -]/p), (p[over -]/e^{+}), and (p/e^{+}) flux ratios show no rigidity
dependence. These are new observations of the properties of elementary particles
in the cosmos.
PMID- 27610854
TI - Spatial Distribution of Phase Singularities in Optical Random Vector Waves.
AB - Phase singularities are dislocations widely studied in optical fields as well as
in other areas of physics. With experiment and theory we show that the vectorial
nature of light affects the spatial distribution of phase singularities in random
light fields. While in scalar random waves phase singularities exhibit spatial
distributions reminiscent of particles in isotropic liquids, in vector fields
their distribution for the different vector components becomes anisotropic due to
the direct relation between propagation and field direction. By incorporating
this relation in the theory for scalar fields by Berry and Dennis [Proc. R. Soc.
A 456, 2059 (2000)], we quantitatively describe our experiments.
PMID- 27610853
TI - Phase Separation and Pair Condensation in a Spin-Imbalanced 2D Fermi Gas.
AB - We study a two-component quasi-two-dimensional Fermi gas with imbalanced spin
populations. We probe the gas at different interaction strengths and
polarizations by measuring the density of each spin component in the trap and the
pair momentum distribution after time of flight. For a wide range of experimental
parameters, we observe in-trap phase separation characterized by the appearance
of a spin-balanced core surrounded by a polarized gas. Our momentum space
measurements indicate pair condensation in the imbalanced gas even for large
polarizations where phase separation vanishes, pointing to the presence of a
polarized pair condensate. Our observation of zero momentum pair condensates in
2D spin-imbalanced gases opens the way to explorations of more exotic superfluid
phases that occupy a large part of the phase diagram in lower dimensions.
PMID- 27610856
TI - Energy Criterion for the Spectral Stability of Discrete Breathers.
AB - Discrete breathers are ubiquitous structures in nonlinear anharmonic models
ranging from the prototypical example of the Fermi-Pasta-Ulam model to Klein
Gordon nonlinear lattices, among many others. We propose a general criterion for
the emergence of instabilities of discrete breathers analogous to the well
established Vakhitov-Kolokolov criterion for solitary waves. The criterion
involves the change of monotonicity of the discrete breather's energy as a
function of the breather frequency. Our analysis suggests and numerical results
corroborate that breathers with increasing (decreasing) energy-frequency
dependence are generically unstable in soft (hard) nonlinear potentials.
PMID- 27610855
TI - Probe of Multielectron Dynamics in Xenon by Caustics in High-Order Harmonic
Generation.
AB - We investigated the giant resonance in xenon by high-order harmonic generation
spectroscopy driven by a two-color field. The addition of a nonperturbative
second harmonic component parallel to the driving field breaks the symmetry
between neighboring subcycles resulting in the appearance of spectral caustics at
two distinct cutoff energies. By controlling the phase delay between the two
color components it is possible to tailor the harmonic emission in order to
amplify and isolate the spectral feature of interest. In this Letter we
demonstrate how this control scheme can be used to investigate the role of
electron correlations that give birth to the giant resonance in xenon. The
collective excitations of the giant dipole resonance in xenon combined with the
spectral manipulation associated with the two-color driving field allow us to see
features that are normally not accessible and to obtain a good agreement between
the experimental results and the theoretical predictions.
PMID- 27610858
TI - Spreading of Bubbles after Contacting the Lower Side of an Aerophilic Slide
Immersed in Water.
AB - While the dynamics of complete wetting has been widely studied for liquids, the
way a gas spreads on a solid is by far less known. We report here the events
following the rise of a millimeter-size air bubble towards a textured material
immersed in water and covered by a thin plastron of air. Bubbles contact the
material either directly at the end of the rise, or after a few rebounds, which
affects the initial shape of the bubble and the resulting dynamics of contact.
Then, air spreads on the material, owing to surface tension and later buoyance,
which tends to flatten further the bubble. The corresponding dynamics are shown
to result from the inertial resistance of water, which explains how spreading
bubbles reach centimeter sizes in typically 10 ms.
PMID- 27610857
TI - Tensile Instability in a Thick Elastic Body.
AB - A range of instabilities can occur in soft bodies that undergo large deformation.
While most of them arise under compressive forces, it has previously been shown
analytically that a tensile instability can occur in an elastic block subjected
to equitriaxial tension. Guided by this result, we conducted centimeter-scale
experiments on thick elastomeric samples under generalized plane strain
conditions and observed for the first time this elastic tensile instability. We
found that equibiaxial stretching leads to the formation of a wavy pattern, as
regions of the sample alternatively flatten and extend in the out-of-plane
direction. Our work uncovers a new type of instability that can be triggered in
elastic bodies, enlarging the design space for smart structures that harness
instabilities to enhance their functionality.
PMID- 27610859
TI - Wave-Based Turing Machine: Time Reversal and Information Erasing.
AB - The investigation of dynamical systems has revealed a deep-rooted difference
between waves and objects regarding temporal reversibility and particlelike
objects. In nondissipative chaos, the dynamic of waves always remains time
reversible, unlike that of particles. Here, we explore the dynamics of a wave
particle entity. It consists in a drop bouncing on a vibrated liquid bath, self
propelled and piloted by the surface waves it generates. This walker, in which
there is an information exchange between the particle and the wave, can be
analyzed in terms of a Turing machine with waves as the information repository.
The experiments reveal that in this system, the drop can read information
backwards while erasing it. The drop can thus backtrack on its previous
trajectory. A transient temporal reversibility, restricted to the drop motion, is
obtained in spite of the system being both dissipative and chaotic.
PMID- 27610860
TI - High-Flux Femtosecond X-Ray Emission from Controlled Generation of Annular
Electron Beams in a Laser Wakefield Accelerator.
AB - Annular quasimonoenergetic electron beams with a mean energy in the range 200-400
MeV and charge on the order of several picocoulombs were generated in a laser
wakefield accelerator and subsequently accelerated using a plasma afterburner in
a two-stage gas cell. Generation of these beams is associated with injection
occurring on the density down ramp between the stages. This well-localized
injection produces a bunch of electrons performing coherent betatron oscillations
in the wakefield, resulting in a significant increase in the x-ray yield. Annular
electron distributions are detected in 40% of shots under optimal conditions.
Simultaneous control of the pulse duration and frequency chirp enables
optimization of both the energy and the energy spread of the annular beam and
boosts the radiant energy per unit charge by almost an order of magnitude. These
well-defined annular distributions of electrons are a promising source of high
brightness laser plasma-based x rays.
PMID- 27610861
TI - Laboratory Observation of Resistive Electron Tearing in a Two-Fluid Reconnecting
Current Sheet.
AB - The spontaneous formation of plasmoids via the resistive electron tearing of a
reconnecting current sheet is observed in the laboratory. These experiments are
performed during driven, antiparallel reconnection in the two-fluid regime within
the Magnetic Reconnection Experiment. It is found that plasmoids are present even
at a very low Lundquist number, and the number of plasmoids scales with both the
current sheet aspect ratio and the Lundquist number. The reconnection electric
field increases when plasmoids are formed, leading to an enhanced reconnection
rate.
PMID- 27610862
TI - Explosive Particle Dispersion in Plasma Turbulence.
AB - Particle dynamics are investigated in plasma turbulence, using self-consistent
kinetic simulations, in two dimensions. In the steady state, the trajectories of
single protons and proton pairs are studied, at different values of plasma beta
(ratio between kinetic and magnetic pressure). For single-particle displacements,
results are consistent with fluids and magnetic field line dynamics, where
particles undergo normal diffusion for very long times, with higher beta's being
more diffusive. In an intermediate time range, with separations lying in the
inertial range, particles experience an explosive dispersion in time, consistent
with the Richardson prediction. These results, obtained for the first time with a
self-consistent kinetic model, are relevant for astrophysical and laboratory
plasmas, where turbulence is crucial for heating, mixing, and acceleration
processes.
PMID- 27610863
TI - Observation and Structure Determination of an Oxide Quasicrystal Approximant.
AB - We report on the first observation of an approximant structure to the recently
discovered two-dimensional oxide quasicrystal. Using scanning tunneling
microscopy, low-energy electron diffraction, and surface x-ray diffraction in
combination with ab initio calculations, the atomic structure and the bonding
scheme are determined. The oxide approximant follows a 3^{2}.4.3.4 Archimedean
tiling. Ti atoms reside at the corners of each tiling element and are threefold
coordinated to oxygen atoms. Ba atoms separate the TiO_{3} clusters, leading to a
fundamental edge length of the tiling 6.7 A.
PMID- 27610864
TI - Premelting-Induced Smoothening of the Ice-Vapor Interface.
AB - We perform computer simulations of the quasiliquid layer of ice formed at the ice
vapor interface close to the ice Ih-liquid-vapor triple point of water. Our study
shows that the two distinct surfaces bounding the film behave at small
wavelengths as atomically rough and independent ice-water and water-vapor
interfaces. For long wavelengths, however, the two surfaces couple, large scale
parallel fluctuations are inhibited, and the ice-vapor interface becomes smooth.
Our results could help explain the complex morphology of ice crystallites.
PMID- 27610865
TI - Dirac Node Lines in Pure Alkali Earth Metals.
AB - Beryllium is a simple alkali earth metal, but has been the target of intensive
studies for decades because of its unusual electron behavior at surfaces. The
puzzling aspects include (i) severe deviations from the description of the nearly
free-electron picture, (ii) an anomalously large electron-phonon coupling effect,
and (iii) giant Friedel oscillations. The underlying origins for such anomalous
surface electron behavior have been under active debate, but with no consensus.
Here, by means of first-principles calculations, we discover that this pure metal
system, surprisingly, harbors the Dirac node line (DNL) that in turn helps to
rationalize many of the existing puzzles. The DNL is featured by a closed line
consisting of linear band crossings, and its induced topological surface band
agrees well with previous photoemission spectroscopy observations on the Be
(0001) surface. We further reveal that each of the elemental alkali earth metals
of Mg, Ca, and Sr also harbors the DNL and speculate that the fascinating
topological property of the DNL might naturally exist in other elemental metals
as well.
PMID- 27610866
TI - Interaction-Driven Spontaneous Quantum Hall Effect on a Kagome Lattice.
AB - Topological states of matter have been widely studied as being driven by an
external magnetic field, intrinsic spin-orbital coupling, or magnetic doping.
Here, we unveil an interaction-driven spontaneous quantum Hall effect (a Chern
insulator) emerging in an extended fermion-Hubbard model on a kagome lattice,
based on a state-of-the-art density-matrix renormalization group on cylinder
geometry and an exact diagonalization in torus geometry. We first demonstrate
that the proposed model exhibits an incompressible liquid phase with doublet
degenerate ground states as time-reversal partners. The explicit spontaneous time
reversal symmetry breaking is determined by emergent uniform circulating loop
currents between nearest neighbors. Importantly, the fingerprint topological
nature of the ground state is characterized by quantized Hall conductance. Thus,
we identify the liquid phase as a quantum Hall phase, which provides a "proof-of
principle" demonstration of the interaction-driven topological phase in a
topologically trivial noninteracting band.
PMID- 27610867
TI - Slowdown of the Electronic Relaxation Close to the Mott Transition.
AB - We investigate the time-dependent reformation of the quasiparticle peak in a
correlated metal near the Mott transition, after the system is quenched into a
hot electron state and equilibrates with an environment which is colder than the
Fermi-liquid crossover temperature. Close to the transition, we identify a purely
electronic bottleneck time scale, which depends on the spectral weight around the
Fermi energy in the bad metallic phase in a nonlinear way. This time scale can be
orders of magnitude larger than the bare and renormalized electronic hopping
time, so that a separation of electronic and lattice time scales may break down.
The results are obtained using nonequilibrium dynamical mean-field theory and a
slave-rotor representation of the Anderson impurity model.
PMID- 27610868
TI - Filling-Enforced Gaplessness in Band Structures of the 230 Space Groups.
AB - Nonsymmorphic symmetries like screws and glides produce electron band touchings,
obstructing the formation of a band insulator and leading, instead, to metals or
nodal semimetals even when the number of electrons in the unit cell is an even
integer. Here, we calculate the electron fillings compatible with being a band
insulator for all 230 space groups, for noninteracting electrons with time
reversal symmetry. Our bounds are tight-that is, we can rigorously eliminate band
insulators at any forbidden filling and produce explicit models for all allowed
fillings-and stronger than those recently established for interacting systems.
These results provide simple criteria that should help guide the search for
topological semimetals and, also, have implications for both the nature and
stability of the resulting nodal Fermi surfaces.
PMID- 27610869
TI - Fermionic Symmetry-Protected Topological Phase in a Two-Dimensional Hubbard
Model.
AB - We study the two-dimensional (2D) Hubbard model using exact diagonalization for
spin-1/2 fermions on the triangular and honeycomb lattices decorated with a
single hexagon per site. In certain parameter ranges, the Hubbard model maps to a
quantum compass model on those lattices. On the triangular lattice, the compass
model exhibits collinear stripe antiferromagnetism, implying d-density wave
charge order in the original Hubbard model. On the honeycomb lattice, the compass
model has a unique, quantum disordered ground state that transforms nontrivially
under lattice reflection. The ground state of the Hubbard model on the decorated
honeycomb lattice is thus a 2D fermionic symmetry-protected topological phase.
This state-protected by time-reversal and reflection symmetries-cannot be
connected adiabatically to a free-fermion topological phase.
PMID- 27610870
TI - Commensurability Oscillations of Composite Fermions Induced by the Periodic
Potential of a Wigner Crystal.
AB - When the kinetic energy of a collection of interacting two-dimensional (2D)
electrons is quenched at very high magnetic fields so that the Coulomb repulsion
dominates, the electrons are expected to condense into an ordered array, forming
a quantum Wigner crystal (WC). Although this exotic state has long been suspected
in high-mobility 2D electron systems at very low Landau level fillings (nu?1),
its direct observation has been elusive. Here we present a new technique and
experimental results directly probing the magnetic-field-induced WC. We measure
the magnetoresistance of a bilayer electron system where one layer has a very low
density and is in the WC regime (nu?1), while the other ("probe") layer is near
nu=1/2 and hosts a sea of composite fermions (CFs). The data exhibit
commensurability oscillations in the magnetoresistance of the CF layer, induced
by the periodic potential of WC electrons in the other layer, and provide a
unique, direct glimpse at the symmetry of the WC, its lattice constant, and
melting. They also demonstrate a striking example of how one can probe an exotic
many-body state of 2D electrons using equally exotic quasiparticles of another
many-body state.
PMID- 27610871
TI - Micrometer-Scale Ballistic Transport of Electron Pairs in LaAlO_{3}/SrTiO_{3}
Nanowires.
AB - High-mobility complex-oxide heterostructures and nanostructures offer new
opportunities for extending the paradigm of quantum transport beyond the realm of
traditional III-V or carbon-based materials. Recent quantum transport
investigations with LaAlO_{3}/SrTiO_{3}-based quantum dots reveal the existence
of a strongly correlated phase in which electrons form spin-singlet pairs without
becoming superconducting. Here, we report evidence for the micrometer-scale
ballistic transport of electron pairs in quasi-1D LaAlO_{3}/SrTiO_{3} nanowire
cavities. In the paired phase, Fabry-Perot-like quantum interference is observed,
in sync with conductance oscillations observed in the superconducting regime (at
a zero magnetic field). Above a critical magnetic field B_{p}, the electron pairs
unbind and the conductance oscillations shift with the magnetic field. These
experimental observations extend the regime of ballistic electronic transport to
strongly correlated phases.
PMID- 27610872
TI - Stabilization of the Particle-Hole Pfaffian Order by Landau-Level Mixing and
Impurities That Break Particle-Hole Symmetry.
AB - Numerical results suggest that the quantum Hall effect at nu=5/2 is described by
the Pfaffian or anti-Pfaffian state in the absence of disorder and Landau-level
mixing. Those states are incompatible with the observed transport properties of
GaAs heterostructures, where disorder and Landau-level mixing are strong. We show
that the recent proposal of a particle-hole (PH)-Pfaffian topological order by
Son is consistent with all experiments. The absence of particle-hole symmetry at
nu=5/2 is not an obstacle to the existence of the PH-Pfaffian order since the
order is robust to symmetry breaking.
PMID- 27610873
TI - Charge 2e/3 Superconductivity and Topological Degeneracies without Localized Zero
Modes in Bilayer Fractional Quantum Hall States.
AB - It has been recently shown that non-Abelian defects with localized parafermion
zero modes can arise in conventional Abelian fractional quantum Hall (FQH)
states. Here we propose an alternate route to creating, manipulating, and
measuring topologically protected degeneracies in bilayer FQH states coupled to
superconductors, without the creation of localized parafermion zero modes. We
focus mainly on electron-hole bilayers, with a +/-1/3 Laughlin FQH state in each
layer, with boundaries that are proximity coupled to a superconductor. We show
that the superconductor induces charge 2e/3 quasiparticle-pair condensation at
each boundary of the FQH state, and that this leads to (i) topologically
protected degeneracies that can be measured through charge sensing experiments
and (ii) a fractional charge 2e/3 ac Josephson effect. We demonstrate that an
analog of non-Abelian braiding is possible, despite the absence of a localized
zero mode. We discuss several practical advantages of this proposal over previous
work, and also several generalizations.
PMID- 27610874
TI - Quantization of Hall Resistance at the Metallic Interface between an Oxide
Insulator and SrTiO_{3}.
AB - The two-dimensional metal forming at the interface between an oxide insulator and
SrTiO_{3} provides new opportunities for oxide electronics. However, the quantum
Hall effect, one of the most fascinating effects of electrons confined in two
dimensions, remains underexplored at these complex oxide heterointerfaces. Here,
we report the experimental observation of quantized Hall resistance in a
SrTiO_{3} heterointerface based on the modulation-doped amorphous
LaAlO_{3}/SrTiO_{3} heterostructure, which exhibits both high electron mobility
exceeding 10,000 cm^{2}/V s and low carrier density on the order of ~10^{12}
cm^{-2}. Along with unambiguous Shubnikov-de Haas oscillations, the spacing of
the quantized Hall resistance suggests that the interface is comprised of a
single quantum well with ten parallel conducting two-dimensional sub-bands. This
provides new insight into the electronic structure of conducting oxide interfaces
and represents an important step towards designing and understanding advanced
oxide devices.
PMID- 27610875
TI - Modifying the Surface of a Rashba-Split Pb-Ag Alloy Using Tailored Metal-Organic
Bonds.
AB - Hybridization-related modifications of the first metal layer of a metal-organic
interface are difficult to access experimentally and have been largely neglected
so far. Here, we study the influence of specific chemical bonds (as formed by the
organic molecules CuPc and PTCDA) on a Pb-Ag surface alloy. We find that
delocalized van der Waals or weak chemical pi-type bonds are not strong enough to
alter the alloy, while localized sigma-type bonds lead to a vertical displacement
of the Pb surface atoms and to changes in the alloy's surface band structure. Our
results provide an exciting platform for tuning the Rashba-type spin texture of
surface alloys using organic molecules.
PMID- 27610876
TI - NaFe_{0.56}Cu_{0.44}As: A Pnictide Insulating Phase Induced by On-Site Coulomb
Interaction.
AB - In the studies of iron pnictides, a key question is whether their bad-metal state
from which the superconductivity emerges lies in close proximity with a
magnetically ordered insulating phase. Recently, it was found that at low
temperatures, the heavily Cu-doped NaFe_{1-x}Cu_{x}As (x>0.3) iron pnictide is an
insulator with long-range antiferromagnetic order, similar to the parent compound
of cuprates but distinct from all other iron pnictides. Using angle-resolved
photoemission spectroscopy, we determined the momentum-resolved electronic
structure of NaFe_{1-x}Cu_{x}As (x=0.44) and identified that its ground state is
a narrow-gap insulator. Combining the experimental results with density
functional theory (DFT) and DFT+U calculations, our analysis reveals that the on
site Coulombic (Hubbard) and Hund's coupling energies play crucial roles in the
formation of the band gap about the chemical potential. We propose that at finite
temperatures, charge carriers are thermally excited from the Cu-As-like valence
band into the conduction band, which is of Fe 3d-like character. With increasing
temperature, the number of electrons in the conduction band becomes larger and
the hopping energy between Fe sites increases, and finally the long-range
antiferromagnetic order is destroyed at T>T_{N}. Our study provides a basis for
investigating the evolution of the electronic structure of a Mott insulator
transforming into a bad metallic phase and eventually forming a superconducting
state in iron pnictides.
PMID- 27610877
TI - Competing Orders in a Nearly Antiferromagnetic Metal.
AB - We study the onset of spin-density wave order in itinerant electron systems via a
two-dimensional lattice model amenable to numerically exact, sign-problem-free
determinantal quantum Monte Carlo simulations. The finite-temperature phase
diagram of the model reveals a dome-shaped d-wave superconducting phase near the
magnetic quantum phase transition. Above the critical superconducting
temperature, an extended fluctuation regime manifests itself in the opening of a
gap in the electronic density of states and an enhanced diamagnetic response.
While charge density wave fluctuations are moderately enhanced in the proximity
of the magnetic quantum phase transition, they remain short ranged. The striking
similarity of our results to the phenomenology of many unconventional
superconductors points a way to a microscopic understanding of such strongly
coupled systems in a controlled manner.
PMID- 27610878
TI - Thermal Conductivity of the Iron-Based Superconductor FeSe: Nodeless Gap with a
Strong Two-Band Character.
AB - The thermal conductivity kappa of the iron-based superconductor FeSe was measured
at temperatures down to 75 mK in magnetic fields up to 17 T. In a zero magnetic
field, the electronic residual linear term in the T=0 K limit, kappa_{0}/T, is
vanishingly small. The application of a magnetic field B causes an exponential
increase in kappa_{0}/T initially. Those two observations show that there are no
zero-energy quasiparticles that carry heat and therefore no nodes in the
superconducting gap of FeSe. The full field dependence of kappa_{0}/T has the
classic two-step shape of a two-band superconductor: a first rise at very low
field, with a characteristic field B^{?}?B_{c2}, and then a second rise up to the
upper critical field B_{c2}. This shows that the superconducting gap is very
small (but finite) on one of the pockets in the Fermi surface of FeSe. We
estimate that the minimum value of the gap, Delta_{min}, is an order of magnitude
smaller than the maximum value, Delta_{max}.
PMID- 27610879
TI - Muon Spin Relaxation Evidence for the U(1) Quantum Spin-Liquid Ground State in
the Triangular Antiferromagnet YbMgGaO_{4}.
AB - Muon spin relaxation (MUSR) experiments on single crystals of the structurally
perfect triangular antiferromagnet YbMgGaO_{4} indicate the absence of both
static long-range magnetic order and spin freezing down to 0.048 K in a zero
field. Below 0.4 K, the MU^{+} spin relaxation rates, which are proportional to
the dynamic correlation function of the Yb^{3+} spins, exhibit temperature
independent plateaus. All these MUSR results unequivocally support the formation
of a gapless U(1) quantum spin liquid ground state in the triangular
antiferromagnet YbMgGaO_{4}.
PMID- 27610880
TI - Dynamic Feedback in Ferromagnet-Spin Hall Metal Heterostructures.
AB - In ferromagnet-normal-metal heterostructures, spin pumping and spin-transfer
torques are two reciprocal processes that occur concomitantly. Their interplay
introduces a dynamic feedback effect interconnecting energy dissipation channels
of both magnetization and current. By solving the spin diffusion process in the
presence of the spin Hall effect in the normal metal, we show that the dynamic
feedback gives rise to (i) a nonlinear magnetic damping that is crucial to
sustain uniform steady-state oscillations of a spin Hall oscillator at large
angles and (ii) a frequency-dependent spin Hall magnetoimpedance that reduces to
the spin Hall magnetoresistance in the dc limit.
PMID- 27610881
TI - Revealing and Characterizing Dark Excitons through Coherent Multidimensional
Spectroscopy.
AB - Dark excitons are of fundamental importance in a broad range of contexts but are
difficult to study using conventional optical spectroscopy due to their weak
interaction with light. We show how coherent multidimensional spectroscopy can
reveal and characterize dark states. Using this approach, we identify parity
forbidden and spatially indirect excitons in InGaAs/GaAs quantum wells and
determine details regarding lifetimes, homogeneous and inhomogeneous linewidths,
broadening mechanisms, and coupling strengths. The observations of coherent
coupling between these states and bright excitons hint at a role for a multistep
process by which excitons in the barrier can relax into the quantum wells.
PMID- 27610882
TI - Phonon-Photon Mapping in a Color Center in Hexagonal Boron Nitride.
AB - We report on the ultraviolet optical response of a color center in hexagonal
boron nitride. We demonstrate a mapping between the vibronic spectrum of the
color center and the phonon dispersion in hexagonal boron nitride, with a
striking suppression of the phonon assisted emission signal at the energy of the
phonon gap. By means of nonperturbative calculations of the electron-phonon
interaction in a strongly anisotropic phonon dispersion, we reach a quantitative
interpretation of the acoustic phonon sidebands from cryogenic temperatures up to
room temperature. Our analysis provides an original method for estimating the
spatial extension of the electronic wave function in a point defect.
PMID- 27610884
TI - Ferroelectricity and Phase Transitions in Monolayer Group-IV Monochalcogenides.
AB - Ferroelectricity usually fades away as materials are thinned down below a
critical value. We reveal that the unique ionic-potential anharmonicity can
induce spontaneous in-plane electrical polarization and ferroelectricity in
monolayer group-IV monochalcogenides MX (M=Ge, Sn; X=S, Se). An effective
Hamiltonian has been successfully extracted from the parametrized energy space,
making it possible to study the ferroelectric phase transitions in a single-atom
layer. The ferroelectricity in these materials is found to be robust and the
corresponding Curie temperatures are higher than room temperature, making them
promising for realizing ultrathin ferroelectric devices of broad interest. We
further provide the phase diagram and predict other potentially two-dimensional
ferroelectric materials.
PMID- 27610883
TI - Talbot Effect for Exciton Polaritons.
AB - We demonstrate, experimentally and theoretically, a Talbot effect for hybrid
light-matter waves-an exciton-polariton condensate formed in a semiconductor
microcavity with embedded quantum wells. The characteristic "Talbot carpet" is
produced by loading the exciton-polariton condensate into a microstructured one
dimensional periodic array of mesa traps, which creates an array of phase-locked
sources for coherent polariton flow in the plane of the quantum wells. The
spatial distribution of the Talbot fringes outside the mesas mimics the near
field diffraction of a monochromatic wave on a periodic amplitude and phase
grating with the grating period comparable to the wavelength. Despite the lossy
nature of the polariton system, the Talbot pattern persists for distances
exceeding the size of the mesas by an order of magnitude. Thus, our experiment
demonstrates efficient shaping of the two-dimensional flow of coherent exciton
polaritons by a one-dimensional "flat lens."
PMID- 27610885
TI - Tube Concept for Entangled Stiff Fibers Predicts Their Dynamics in Space and
Time.
AB - We study dynamically crowded solutions of stiff fibers deep in the semidilute
regime, where the motion of a single constituent becomes increasingly confined to
a narrow tube. The spatiotemporal dynamics for wave numbers resolving the motion
in the confining tube becomes accessible in Brownian dynamics simulations upon
employing a geometry-adapted neighbor list. We demonstrate that in such crowded
environments the intermediate scattering function, characterizing the motion in
space and time, can be predicted quantitatively by simulating a single freely
diffusing phantom needle only, yet with very unusual diffusion coefficients.
PMID- 27610886
TI - Active Particles with Soft and Curved Walls: Equation of State, Ratchets, and
Instabilities.
AB - We study, from first principles, the pressure exerted by an active fluid of
spherical particles on general boundaries in two dimensions. We show that,
despite the nonuniform pressure along curved walls, an equation of state is
recovered upon a proper spatial averaging. This holds even in the presence of
pairwise interactions between particles or when asymmetric walls induce ratchet
currents, which are accompanied by spontaneous shear stresses on the walls. For
flexible obstacles, the pressure inhomogeneities lead to a modulational
instability as well as to the spontaneous motion of short semiflexible filaments.
Finally, we relate the force exerted on objects immersed in active baths to the
particle flux they generate around them.
PMID- 27610887
TI - Tuning Colloid-Interface Interactions by Salt Partitioning.
AB - We show that the interaction of an oil-dispersed colloidal particle with an oil
water interface is highly tunable from attractive to repulsive, either by varying
the sign of the colloidal charge via charge regulation or by varying the
difference in hydrophilicity between the dissolved cations and anions. In
addition, we investigate the yet unexplored interplay between the self-regulated
colloidal surface charge distribution with the planar double layer across the oil
water interface and the spherical one around the colloid. Our findings explain
recent experiments and have direct relevance for tunable Pickering emulsions.
PMID- 27610888
TI - Unifying Impacts in Granular Matter from Quicksand to Cornstarch.
AB - A sharp transition between liquefaction and transient solidification is observed
during impact on a granular suspension depending on the initial packing fraction.
We demonstrate, via high-speed pressure measurements and a two-phase modeling,
that this transition is controlled by a coupling between the granular pile
dilatancy and the interstitial fluid pressure generated by the impact. Our
results provide a generic mechanism for explaining the wide variety of impact
responses in particulate media, from dry quicksand in powders to impact hardening
in shear-thickening suspensions like cornstarch.
PMID- 27610889
TI - Crystallization of Self-Propelled Hard Discs.
AB - We experimentally study the crystallization of a monolayer of vibrated discs with
a built-in polar asymmetry, a model system of active liquids, and contrast it
with that of vibrated isotropic discs. Increasing the packing fraction phi, the
quasicontinuous crystallization reported for isotropic discs is replaced by a
transition, or a crossover, towards a "self-melting" crystal. Starting from the
liquid phase and increasing the packing fraction, clusters of dense hexagonal
ordered packed discs spontaneously form, melt, split, and merge, leading to a
highly intermittent and heterogeneous dynamics. For a packing fraction larger
than phi^{*}, a few large clusters span the system size. The cluster size
distribution is monotonically decreasing for phiphi^{*}, and is a power law at the transition. The system is, however, never
dynamically arrested. The clusters permanently melt from place to place, forming
droplets of an active liquid which rapidly propagate across the system. This self
melting crystalline state subsists up to the highest possible packing fraction,
questioning the stability of the crystal for active discs unless it is at ordered
close packing.
PMID- 27610890
TI - Quantifying Interparticle Forces and Heterogeneity in 3D Granular Materials.
AB - Interparticle forces in granular materials are intimately linked to mechanical
properties and are known to self-organize into heterogeneous structures, or force
chains, under external load. Despite progress in understanding the statistics and
spatial distribution of interparticle forces in recent decades, a systematic
method for measuring forces in opaque, three-dimensional (3D), frictional, stiff
granular media has yet to emerge. In this Letter, we present results from an
experiment that combines 3D x-ray diffraction, x-ray tomography, and a numerical
force inference technique to quantify interparticle forces and their
heterogeneity in an assembly of quartz grains undergoing a one-dimensional
compression cycle. Forces exhibit an exponential decay above the mean and
partition into strong and weak networks. We find a surprising inverse
relationship between macroscopic load and the heterogeneity of interparticle
forces, despite the clear emergence of two force chains that span the system.
PMID- 27610891
TI - Thermal Convection in Granular Gases with Dissipative Lateral Walls.
AB - We consider a granular gas under the action of gravity, fluidized by a vibrating
base. We show that a horizontal temperature gradient, here induced by limiting
dissipative lateral walls (DLW), leads always to a granular thermal convection
(DLW TC) that is essentially different from ordinary bulk-buoyancy-driven
convection (BBD TC). In an experiment where BBD TC is inhibited, by reducing
gravity with an inclined plane, we always observe a DLW TC cell next to each
lateral wall. Such a cell squeezes towards the nearest wall as the gravity and/or
the number of grains increase. Molecular dynamics simulations reproduce the
experimental results and indicate that at large gravity or number of grains the
DLW TC is barely detectable.
PMID- 27610892
TI - Erratum: Testing Nonassociative Quantum Mechanics [Phys. Rev. Lett. 115, 220402
(2015)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.115.220402.
PMID- 27610893
TI - Erratum: Spectroscopic Quadrupole Moments in ^{96,98}Sr: Evidence for Shape
Coexistence in Neutron-Rich Strontium Isotopes at N=60 [Phys. Rev. Lett. 116,
022701 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.116.022701.
PMID- 27610894
TI - Phase I dose-escalation study of plitidepsin in combination with bevacizumab in
patients with refractory solid tumors.
AB - This phase I trial evaluated the toxicity profile and maximum tolerated dose of
the combination between the marine derived cyclodepsipeptide plitidepsin and
bevacizumab in advanced cancer patients. Thirteen patients were enrolled and
treated with plitidepsin at three dose levels (2.8 mg/m, n=3; 3.8 mg/m, n=4; and
4.8 mg/m, n=6) with a fixed dose of bevacizumab (10 mg/kg). Both agents were
administered intravenously at D1 and D15 of a 28-day cycle. All 13 patients were
evaluable for safety and toxicity. Dose-limiting toxicities occurred in two out
of six patients treated at the maximum dose tested (plitidepsin 4.8 mg/m and
bevacizumab 10 mg/kg) and consisted of grade 3 fatigue, grade 3 myalgia, and two
grade 2/3 alanine aminotransferase increases lasting for more than 7 days or
leading to subsequent cycle delay greater than 2 weeks (n=1 each). The
recommended dose for the combination of plitidepsin with bevacizumab was 3.8 mg/m
for plitidepsin and 10 mg/kg for bevacizumab every 2 weeks. Most frequent
treatment-related adverse events were nausea, vomiting, fatigue, epistaxis, and
headache. Relevant hematological toxicity was minimal. Objective disease
responses were not observed; however, stable disease (>3 months) was observed in
four patients with colorectal cancer, renal cancer, and cervical cancer.
Combining plitidepsin with bevacizumab combination is feasible. Stable disease
was the best response obtained.
PMID- 27610895
TI - Association between genes on chromosome 19p13.2 and panic disorder.
AB - Panic disorder (PD) is a severe and disabling mental disorder, which is
moderately heritable. In a previous study, we carried out a genome-wide
association study using patients with PD and control individuals from the
isolated population of the Faroe Islands and identified chromosome 19p13.2 as a
candidate region. To further investigate this chromosomal region for association
with PD, we analysed eight single nucleotide polymorphisms (SNPs) in three
candidate genes - small-nuclear RNA activating complex, polypeptide 2 (SNAPC2),
mitogen-activated protein kinase kinase 7 (MAP2K7) and leucine-rich repeat
containing 8 family, member E (LRRC8E) - these genes have previously been
directly or indirectly implicated in other mental disorders. A total of 511
patients with PD and 1029 healthy control individuals from the Faroe Islands,
Denmark and Germany were included in the current study. SNPs covering the gene
region of SNAPC2, MAP2K7 and LRRC8E were genotyped and tested for association
with PD. In the Faroese cohort, rs7788 within SNAPC2 was significantly associated
with PD, whereas rs3745383 within LRRC8E was nominally associated. No association
was observed between the analysed SNPs and PD in the Danish cohorts. In the
German women, we observed a nominal association between rs4804833 within MAP2K7
and PD. We present further evidence that chromosome 19p13.2 may harbour candidate
genes that contribute towards the risk of developing PD. Moreover, the
implication of the associated genes in other mental disorders may indicate shared
genetic susceptibility between mental disorders. We show that associated variants
may be sex specific, indicating the importance of carrying out a sex-specific
association analysis of PD.
PMID- 27610896
TI - Significant Moments.
PMID- 27610897
TI - NCF @ Work.
PMID- 27610898
TI - Etc.
PMID- 27610899
TI - Aging Gracefully.
PMID- 27610900
TI - Nursing in the Church.
PMID- 27610901
TI - Student TXT.
PMID- 27610902
TI - Dying Healthy.
PMID- 27610903
TI - Trauma-Informed Care: Helping Patients with a Painful Past.
AB - Life trauma is highly correlated with an increased risk of mortality from chronic
disease. Trauma-informed care (TIC) is an evidence-based approach to deliver
healthcare in a way that recognizes and responds to the long-term health effects
of the experience of trauma in patients' lives. Four essential features and six
defining concepts delineate a TIC approach to healthcare. Nurses can realize the
benefits and learn the tenets of TIC to deliver superior care to patients with
chronic illness.
PMID- 27610904
TI - Perceptions of Spirituality and Spiritual Care in Religious Nurses.
AB - This study explored nurses' perceptions of how they provide spiritual care, the
barriers to delivering spiritual care, and the adequacy of their education and
training on spiritual care. Past and current students from a faith-based
university nursing program completed an online survey (N = 614). Participants
reported varying definitions of spirituality and view spiritual care practices
through a wide lens. The majority believed nurses do not receive sufficient
spiritual education but reported they usually feel able to meet patients'
spiritual needs. Time limitations were the most frequent obstacle to providing
spiritual care.
PMID- 27610905
TI - Spiritual Darkness: Reflections on a Medical Mission.
AB - This is a reflective analysis on the lived experience of a medical mission in a
third world country, where young women are abused and trafficked for sex.
Practices of Scripture study, Lectio Divina, and contemplative prayer enabled me
to deal with the spiritual darkness we encountered. Opening a dialogue with
community members to view males and females in a different manner and battling
alongside the local mission and ministers against sex trafficking, are not easy
tasks. The perseverance found in the Bible gives us hope to be witnesses and
healers in our broken world, and a small part in change that can take root with
prayer.
PMID- 27610906
TI - Improving Health Through Political Activism.
AB - Nurse leaders have a moral and professional obligation to be aware of and
influence policy to promote health at local to national levels. As nurse leaders
and concerned local residents, the authors engaged in changing the influence of a
sexually-oriented business that was impacting the psychosocial health of local
citizenry, especially children. Learning city ordinances and state and federal
laws was a precursor to change. Professionalism in action can successfully engage
community leaders, create change, and support community health.
PMID- 27610907
TI - Equipping African American Clergy to Recognize Depression.
AB - Many African Americans (AAs) use clergy as their primary source of help for
depression, with few being referred to mental health providers. This study used
face-to-face workshops to train AA clergy to recognize the symptoms and levels of
severity of depression. A pretest/posttest format was used to test knowledge (N =
42) about depression symptoms. Results showed that the participation improved the
clergy's ability to recognize depression symptoms. Faith community nurses can
develop workshops for clergy to improve recognition and treatment of depression.
PMID- 27610908
TI - Strategies for Providing Spiritual Care & Support to Nursing Students.
AB - Nurse educators need to equip nursing students with suitable resources and
education so they can develop their own spiritual care, as well as recognize
spiritual care needs in patients. There is a paucity of literature on teaching
strategies for spiritual care and prayer in undergraduate nursing programs. This
article describes how one faith-based school implemented strategies to facilitate
spiritual development in students, which are integrated throughout the curriculum
and utilized in the U.S. and a study-abroad program in Ireland.
PMID- 27610909
TI - Nursing in the Mercy Traditions: Engaging Students in the Life of Catherine
McAuley.
AB - The Institute of Medicine and the American Association of Colleges of Nursing
advise that professional nursing education include development of a high level of
cultural competency. A 10-day learning experience to Ireland for nursing students
at the University of Detroit Mercy, an independent Catholic university, sponsored
by the Sisters of Mercy and the Society of Jesus (Jesuit Fathers), helped them
develop a philosophy of Mercy care and build cultural competence. Learning
focused on the life of Catherine McAuley, Irish culture, spirituality, social
justice, reflective thinking, and a value-centered professional education.
PMID- 27610910
TI - Focus on Your Feelings.
PMID- 27610911
TI - FAQs: How Do We Listen Deeply?
PMID- 27610912
TI - Purpose or Paycheck?
PMID- 27610913
TI - Surprised by Prayer.
PMID- 27610914
TI - Resources.
PMID- 27610915
TI - PulseBeats.
PMID- 27610916
TI - Model for a Healthy Work Environment.
AB - The Healthy Work Environment (HWE) Model, considered a model of standards of
professional behaviors, was created to help foster an environment that is happy,
healthy, realistic, and feasible. The model focuses on areas of PEOPLE and
PRACTICE, where each letter of these words identifies core, professional
qualities and behaviors to foster an environment amenable and conducive to
accountability for one's behavior and action. Each of these characteristics is
supported from a Christian, biblical perspective. The HWE Model provides a mental
and physical checklist of what is important in creating and sustaining a healthy
work environment in education and practice.
PMID- 27610917
TI - Discovering Their Needs: Southern Rural Women of East India.
AB - This qualitative, descriptive, phenomenological study explored how southern,
rural women in India (N = 14) view health, how they learned about health, and
what health education they desired. Health education classes were offered, based
on participants' responses. Recommendations are offered for a best practice model
that could potentially enhance the efforts of non-Indian nurses desiring to
assist impoverished women and families in India.
PMID- 27610918
TI - Trauma-Informed Care: Helping Patients with a Painful Past.
PMID- 27610919
TI - Equipping African American Clergy to Recognize Depression.
PMID- 27610920
TI - Affordable headphones for accessible screening audiometry: An evaluation of the
Sennheiser HD202 II supra-aural headphone.
AB - OBJECTIVE: Evaluation of the Sennheiser HD 202 II supra-aural headphones as an
alternative headphone to enable more affordable hearing screening. DESIGN: Study
1 measured the equivalent threshold sound pressure levels (ETSPL) of the
Sennheiser HD 202 II. Study 2 evaluated the attenuation of the headphones. Study
3 determined headphone characteristics by analyzing the total harmonic distortion
(THD), frequency response and force of the headband. STUDY SAMPLE: Twenty-five
participants were included in study 1 and 15 in study 2 with ages ranging between
18 and 25. No participants were involved in study 3. RESULTS: The Sennheiser HD
202 II ETSPLs (250-16000 Hz) showed no significant effects on ETSPL for ear
laterality, gender or age. Attenuation was not significantly different (p > 0.01)
to TDH 39 except at 8000 Hz (p < 0.01). Maximum permissible ambient noise levels
(MPANL) were specified accordingly. The force of the headband was 3.1N. THD
measurements showed that between 500 and 8000 Hz intensities of 90 dB HL and
higher can be reached without THD >3%. CONCLUSION: Sennheiser HD 202 II supra
aural headphones can be used as an affordable headphone for screening audiometry
provided reported MPANLs, maximum intensities and ETSPL values are employed.
PMID- 27610922
TI - The Role of Nanoscale Seed Layers on the Enhanced Performance of Niobium doped
TiO2 Thin Films on Glass.
AB - Transparent conducting oxide (TCO) coatings with decreased cost and greater
process or performance versatility are needed for a variety of optoelectronic
applications. Among potential new TCO candidates, doped titanium dioxide is
receiving particular interest. In this study, niobium-doped titania bilayer
structures consisting of a nanoscale seed layer (deposited by atomic layer
deposition or RF magnetron sputtering) followed by a thick bulk-like layer were
grown directly on glass in order to examine the effects of the seed layer
processing on the subsequent crystallization and electrical properties of these
heterostructures. Observations from Raman spectroscopy suggest that higher oxygen
content in the seed layer suppresses the formation of detrimental titania
polymorph phases, found in films produced by annealing directly after synthesis
without any exposure to oxygen. Furthermore, our results indicate that the
generation of excellent Nb:TiO2 conductors on glass (without breaking vacuum)
only occurs within a narrow processing range and that the sequential deposition
of oxygen-poor layers on oxygen-rich layers is a critical step towards achieving
films with low resistivity.
PMID- 27610921
TI - Mechanically activated artificial cell by using microfluidics.
AB - All living organisms sense mechanical forces. Engineering mechanosensitive
artificial cell through bottom-up in vitro reconstitution offers a way to
understand how mixtures of macromolecules assemble and organize into a complex
system that responds to forces. We use stable double emulsion droplets
(aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to
demonstrate mechanosensation in artificial cells, we develop a novel microfluidic
device that is capable of trapping double emulsions into designated chambers,
followed by compression and aspiration in a parallel manner. The microfluidic
device is fabricated using multilayer soft lithography technology, and consists
of a control layer and a deformable flow channel. Deflections of the PDMS
membrane above the main microfluidic flow channels and trapping chamber array are
independently regulated pneumatically by two sets of integrated microfluidic
valves. We successfully compress and aspirate the double emulsions, which result
in transient increase and permanent decrease in oil thickness, respectively.
Finally, we demonstrate the influx of calcium ions as a response of our
mechanically activated artificial cell through thinning of oil. The development
of a microfluidic device to mechanically activate artificial cells creates new
opportunities in force-activated synthetic biology.
PMID- 27610923
TI - Three order increase in scanning speed of space charge-controlled KTN deflector
by eliminating electric field induced phase transition in nanodisordered KTN.
AB - In this paper, we report a three orders-of-magnitude increase in the speed of a
space-charge-controlled KTN beam deflector achieved by eliminating the electric
field-induced phase transition (EFIPT) in a nanodisordered KTN crystal.
Previously, to maximize the electro-optic effect, a KTN beam deflector was
operated at a temperature slightly above the Curie temperature. The electric
field could cause the KTN to undergo a phase transition from the paraelectric
phase to the ferroelectric phase at this temperature, which causes the deflector
to operate in the linear electro-optic regime. Since the deflection angle of the
deflector is proportional to the space charge distribution but not the magnitude
of the applied electric field, the scanning speed of the beam deflector is
limited by the electron mobility within the KTN crystal. To overcome this speed
limitation caused by the EFIPT, we propose to operate the deflector at a
temperature above the critical end point. This results in a significant increase
in the scanning speed from the microsecond to nanosecond regime, which represents
a major technological advance in the field of fast speed beam scanners. This can
be highly beneficial for many applications including high-speed imaging,
broadband optical communications, and ultrafast laser display and printing.
PMID- 27610924
TI - 7th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis.
AB - 7th Annual Symposium on Clinical & Pharmaceutical Solutions through Analysis,
Renaissance Shanghai Pudong Hotel, Shanghai, China, 20-23 April 2016 The 7th
Annual Shanghai Symposium on Innovative Approaches to Reduce Attrition and
Predict Clinical Outcomes (CPSA Shanghai 2016) was held on 20-23 April 2016 in
Renaissance Shanghai Pudong Hotel, Shanghai, China. The meeting was featured with
highly interactive events including diversified symposia, round table
discussions, workshops, poster sessions and conference awards. There were over
220 participants from more than ten countries, with 61 oral presentations and 29
posters presented. In addition, the meeting included one preconference workshop
and three joint sessions held with bioanalytical experts from local communities.
PMID- 27610925
TI - NatA is required for suspensor development in Arabidopsis.
AB - Suspensor development is essential for early embryogenesis. The filamentous
suspensor plays vital roles in supporting the embryo proper and in exchanging
nutrients and information between the embryo proper and embryo sac. In addition,
at the globular stage, the uppermost suspensor cell differentiates into the
hypophysis, which generates the progenitors of the quiescent center and columella
stem cells. In naa10 and naa15 mutant plants, suspensor cell identity was found
to be abnormal and embryo development was disturbed, leading to embryonic
lethality. Therefore, the NatA complex is required for proper suspensor
development in Arabidopsis.
PMID- 27610926
TI - Terahertz time-gated spectral imaging for content extraction through layered
structures.
AB - Spatial resolution, spectral contrast and occlusion are three major bottlenecks
for non-invasive inspection of complex samples with current imaging technologies.
We exploit the sub-picosecond time resolution along with spectral resolution
provided by terahertz time-domain spectroscopy to computationally extract
occluding content from layers whose thicknesses are wavelength comparable. The
method uses the statistics of the reflected terahertz electric field at
subwavelength gaps to lock into each layer position and then uses a time-gated
spectral kurtosis to tune to highest spectral contrast of the content on that
specific layer. To demonstrate, occluding textual content was successfully
extracted from a packed stack of paper pages down to nine pages without human
supervision. The method provides over an order of magnitude enhancement in the
signal contrast and can impact inspection of structural defects in wooden
objects, plastic components, composites, drugs and especially cultural artefacts
with subwavelength or wavelength comparable layers.
PMID- 27610927
TI - Sleep Architecture Relates to Daytime Affect and Somatic Complaints in Clinically
Anxious but Not Healthy Children.
AB - It is increasingly clear that seminal sleep-affective relationships begin to take
root in childhood, yet studies exploring how nighttime sleep characteristics
relate to daytime affective symptoms, both in clinical and healthy populations of
children, are lacking. The current study sought to explore these relationships by
investigating whether trait-like and/or daily reports of affective and somatic
symptoms of children with generalized anxiety disorder and matched controls
relate to sleep architecture. Sixty-six children (ages 7-11; 54.4% female; 56.1%
Caucasian; 18.2% biracial; 6.1% African American; 3% Asian; 16.7% Hispanic)
participated including 29 with primary generalized anxiety disorder (without
comorbid depression) and 37 healthy controls matched on age and race/ethnicity.
Participants underwent structured diagnostic assessments including child-report
measures and subsequently reported on their negative affect and somatic symptoms
over the course of 1 week. Children also completed 1 night of polysomnography.
Among children with generalized anxiety disorder only, greater amounts of slow
wave sleep corresponded with less negative affect, and greater amounts of rapid
eye movement sleep was related to more somatic complaints across the week.
Similarly, for trait-like measures, more rapid eye movement sleep and shorter
latency to rapid eye movement sleep were related to greater depressive symptoms
in the anxious group only. The current findings suggest that physiologic sleep
characteristics may contribute in direct ways to the symptom profiles of
clinically anxious children. The functional relevance of such findings (e.g., how
specific sleep characteristics serve to either increase or reduce long-term risk)
is a vital direction for future research.
PMID- 27610928
TI - Recent advances in stable isotope-enabled mass spectrometry-based plant
metabolomics.
AB - Methods employing isotope labeled compounds have been an important part of the
bioanalytical canon for many decades. The past fifteen years have seen the
development of many new approaches using stable (non-radioactive) isotopes as
labels for high-throughput bioanalytical, 'omics-scale' measurements of
metabolites (metabolomics) and proteins (proteomics). This review examines stable
isotopic labeling approaches that have been developed for labeling whole intact
plants, plant tissues, or crude extracts of plant materials with stable isotopes
(mainly using 2H, 13C, 15N, 18O or 34S). The application of metabolome-scale
labeling for improving metabolite annotation, metabolic pathway elucidation, and
relative quantification in mass spectrometry-based metabolomics of plants is also
reviewed.
PMID- 27610929
TI - Serum Calprotectin Expression as a Diagnostic Marker for Sepsis in Postoperative
Intensive Care Unit Patients.
AB - The research was performed to explore the diagnosis value of dynamic serum
calprotectin (SC) expression for sepsis in postoperative intensive care unit
patients. One hundred sixty-three patients who met the inclusion criteria served
as the study group. All cases in the study group were further divided into the
sepsis subgroup (51 cases) and the nonsepsis subgroup (112 cases). Fifty healthy
volunteers served as the control group. The levels of SC and other laboratory
indexes including complete blood counts, leukocytes, the immature-to-total
neutrophil ratio, procalcitonin (PCT), C-reactive protein, and blood lactate were
detected, cytokines [interleukin (IL)-2, IL-6, and interferon-gamma] released by
neutrophils were also determined. The Acute Physiology and Chronic Health
Evaluation II (APACHE II) score and the Sequential Organ Failure Assessment score
were calculated. The factors related to prognosis were analyzed with multivariate
logistic regression analysis. The diagnostic accuracies of DeltaSC [the
differences of SC levels between postoperative day (POD) 1 and POD 2, 3, 5, 7]
and DeltaPCT (the differences of PCT levels between POD 1 and POD 2, 3, 5, 7) on
sepsis were compared with other markers for sepsis. The levels of SC and
cytokines were markedly increased on POD 1, 2, 3, 5, and 7 in the study group
compared with the control group (P < 0.05 or P < 0.01). The same results were
found in the sepsis subgroup compared with the nonsepsis subgroup (P < 0.05 or P
< 0.01). Significant positive correlations between SC and cytokines were
confirmed in patients of the study group (P < 0.05 or P < 0.01). APACHE II scores
and the levels of SC and PCT on POD 1 were the variables significantly associated
with sepsis. The diagnostic accuracies of DeltaSC1-3 (sensitivity 87%,
specificity 89%) and DeltaPCT1-3 (sensitivity 89%, specificity 90%) for sepsis
were greater than other DeltaSCs and DeltaPCTs. It appears that the dynamic
changes in SC are of the predictive values for septic patients after major
surgeries.
PMID- 27610930
TI - Implications of handling practices on the ecotoxic profile of alumina
nanoparticles towards the bacteria Vibrio fischeri.
AB - The complex nature and behavior of Engineered Nanomaterials (ENMs) has led to
adoption of customized experimental ecotoxicity practices that are prone to
possible artefacts in the inherent toxic properties of ENMs. In addition, the
lack of standardized handling procedures for the ecotoxicity testing of ENMs
prevents the development of experimental protocols for regulatory purposes. In
this study, a suite of techniques for dispersion of ENMs was adopted and tested
for two types of surface-modified alumina nanoparticles-one hydrophobic and one
hydrophilic-towards the bacteria, Vibrio fischeri. The effect of certain handling
practices on the observed ecotoxic effects on V. fischeri was examined. The
overall goal was to evaluate by what means the handling practices of ENMs may
affect the obtained toxicity results. It was realized that the toxicity of the
hydrophilic and hydrophobic ENMs was mainly affected by the centrifugation and
the salinity of the tested dispersions, respectively. It is more likely that both
aluminium and coating substance contributed to the overall toxicity. Toxicity
results are discussed with regard to generic physicochemical characteristics of
the dispersions.
PMID- 27610931
TI - rRNAFilter: A Fast Approach for Ribosomal RNA Read Removal Without a Reference
Database.
AB - Metatranscriptomics studies the transcriptome of all microbial species in a
habitat. Removing ribosomal RNA (rRNA) reads in metatranscriptomic data is
essential for the study of microbial gene expression. Although several methods
are developed, all of them rely on rRNA databases that contain a limited number
of known rRNA sequences and cannot work well on rRNA reads from unknown rRNA
sequences. To address this problem, we have developed a novel approach called
rRNAFilter. Our method can accurately and rapidly remove rRNA reads from
metatranscriptomes without any prior knowledge of known rRNA sequences. Compared
with two existing approaches, rRNAFilter has shown comparable performance when
working on reads from known rRNA sequences and much better performance when
dealing with reads from unknown rRNA sequences.
PMID- 27610932
TI - Impact of latest generation cardiac interventional X-ray equipment on patient
image quality and radiation dose for trans-catheter aortic valve implantations.
AB - OBJECTIVES: This study aimed to determine the impact on radiation dose and image
quality of a new cardiac interventional X-ray system for trans-catheter aortic
valve implantation (TAVI) patients compared to the previously-used cardiac X-ray
system. METHODS: Patient dose and image data were retrospectively collected from
a Philips AlluraClarity (new) and Siemens Axion Artis (reference) X-ray system.
Patient dose area product (DAP) and fluoroscopy duration of 41 patient cases from
each X-ray system were compared using a Wilcoxon test. Ten patient aortograms
from each X-ray system were scored by 32 observers on a continuous scale to
assess the clinical image quality at the given phase of the TAVI procedure.
Scores were dichotomised by acceptability and analysed using a Chi-squared test.
RESULTS: Significant reductions in patient dose (p << 0.001) were found for the
new system with no significant change in fluoroscopy duration (p = 0.052);
procedure DAP reduced by 55%, fluoroscopy DAP by 48% and "cine" acquisition DAP
by 61%. There was no significant difference between image quality scores of the
two X-ray systems (p = 0.06). CONCLUSIONS: The new cardiac X-ray system
demonstrated a very significant reduction in patient dose with no loss of
clinical image quality. Advances in Knowledge: The huge growth of TAVI may impact
on the radiation exposure of cardiac patients and particularly on operators
including anaesthetists; cumulative exposure of interventional cardiologists
performing high volume TAVI over 30-40 years may be harmful. The Phillips Clarity
upgrade including improved image enhancement and optimised X-ray settings
significantly reduced radiation without reducing clinically acceptable image
quality.
PMID- 27610934
TI - Quantitative Diffusion-weighted Imaging of the Bone Marrow: An Adjunct Tool for
the Diagnosis of a Diffuse MR Imaging Pattern in Patients with Multiple Myeloma.
AB - Purpose To evaluate the apparent diffusion coefficients (ADCs) of magnetic
resonance (MR) imaging patterns in the bone marrow of patients with multiple
myeloma (MM) and to determine a threshold ADC that may help distinguish a diffuse
from a normal pattern with high accuracy. Materials and Methods This prospective
study was approved by the ethics review board, and informed consent was obtained.
Ninety-nine patients with newly diagnosed, untreated MM and 16 healthy control
subjects underwent spinal MR imaging including diffusion-weighted imaging, and
bone marrow ADCs were calculated. Pattern assignment was based on visual
assessment of conventional MR images. The Kruskal-Wallis H test, the Mann-Whitney
test, and the one-way analysis of variance were used to compare ADCs between
patient subsets and control subjects, and a receiver operating characteristic
analysis was performed. Results Mean ADCs +/- standard deviation in patients with
MM for the normal, focal, and diffuse MR imaging patterns were 0.360 * 10-3
mm2/sec +/- 0.110, 1.046 * 10-3 mm2/sec +/- 0.232, and 0.770 * 10-3 mm2/sec +/-
0.135, respectively. There were significant differences in ADCs between diffuse
and normal (P < .001), diffuse and focal (P < .001), and focal and normal (P <
.001) patterns. Patients with a diffuse pattern had more features of advanced
disease, higher international staging system score, increased incidence of high
risk cytogenetics, and higher revised international staging system score. ADCs
greater than 0.548 * 10-3 mm2/sec showed 100% sensitivity (26 of 26) and 98%
specificity (48 of 49) for the diagnosis of a diffuse (vs normal) MR imaging
pattern, whereas an ADC greater than 0.597 * 10-3 mm2/sec showed 96% sensitivity
(25 of 26) and 100% specificity (49 of 49). Conclusion ADCs of MR imaging
patterns in patients with MM differ significantly. A diffuse MR imaging pattern
can be distinguished more objectively from a normal MR imaging pattern by adding
quantitative diffusion-weighted imaging to standard MR imaging protocols. (c)
RSNA, 2016 Online supplemental material is available for this article.
PMID- 27610933
TI - Cell cycle regulation of embryonic stem cells and mouse embryonic fibroblasts
lacking functional Pax7.
AB - The transcription factor Pax7 plays a key role during embryonic myogenesis and in
adult organisms in that it sustains the proper function of satellite cells, which
serve as adult skeletal muscle stem cells. Recently we have shown that lack of
Pax7 does not prevent the myogenic differentiation of pluripotent stem cells. In
the current work we show that the absence of functional Pax7 in differentiating
embryonic stem cells modulates cell cycle facilitating their proliferation.
Surprisingly, deregulation of Pax7 function also positively impacts at the
proliferation of mouse embryonic fibroblasts. Such phenotypes seem to be executed
by modulating the expression of positive cell cycle regulators, such as cyclin E.
PMID- 27610935
TI - Gender differences in snus versus nicotine gum for cigarette avoidance among a
sample of US smokers.
AB - INTRODUCTION: Women are more susceptible to the harmful effects of cigarette
smoking. Thus, identifying effective harm reduction approaches for women is
necessary. The goal of this project was to examine gender differences in response
to snus versus nicotine gum for cigarette avoidance, as a means of harm
reduction. METHODS: Participants were randomly assigned to use snus or nicotine
gum as a method to avoid cigarette smoking. Participants attended clinic visits
to receive study product, as well as provide biological samples to assess smoking
avoidance and biomarkers and report on use of study product and cigarettes. A
secondary analysis comparing men and women by randomization to study product was
conducted. RESULTS: Participants (n=391; 47% women) were randomized into the snus
group (n=196; 45% women) and the gum group (n=195; 49% women). Men used more snus
whereas women used more gum (p=0.02). During treatment, men in the snus group had
higher total nicotine equivalent values whereas women did not vary by group
(p=0.03). Overall, fewer men in the snus group completely avoided cigarettes
compared to men in the gum group (e.g., continuous abstinence at Week 12: odds
ratio=0.43, 95% confidence interval=0.20-0.93). Among women, there were no
differences by randomization in cigarette avoidance. CONCLUSIONS: Despite a
number of gender differences in response to snus versus nicotine gum, these data
suggest that snus may not be an optimal harm reduction approach for either
gender.
PMID- 27610936
TI - Changes in drinking patterns during and after pregnancy among mothers of children
with fetal alcohol syndrome: A study in three districts of South Africa.
AB - BACKGROUND: Mixed ancestry populations in South Africa have amongst the highest
rates of fetal alcohol syndrome (FAS) worldwide. Defining the drinking patterns
of women with a FAS child guides FAS preventive interventions. METHODS: Data were
drawn from FAS prevalence surveys conducted in three districts: Witzenberg (Cape
Winelands), Frances Baard (inland mining town) and Saldanha Bay (coastal towns).
156 mothers and 50 proxy informants of school-entry children diagnosed with FAS
and partial-FAS were interviewed, and compared with 55 controls recruited in
Saldanha Bay. RESULTS: Study participants were of low socio-economic status
(SES), and a majority of children were either in foster care (12%) or had been
cared for by relatives for long periods (44%). Of cases, 123/160 (77%) reported
current drinking, similar between sites. During pregnancy, only 35% (49/139) of
cases had stopped drinking, varying between sites (from 21% to 54% in
chronological order of surveys; p<0.001), while 6% (7/109) increased drinking.
Though many women who stopped in pregnancy resumed postpartum, cessation in
pregnancy was strongly associated with discontinuation in the long run (OR=3.3;
95%CI=1.2-8.9; p=0.005). At interview, 36% of cases (54/151) and 18% of controls
(9/51) were at risk of an alcohol-exposed pregnancy (p=0.02). Median maternal
mass of cases was 22kg lower than controls, with 20% being underweight and 14%
microcephalic. CONCLUSIONS: Increasing rates of drinking cessation during
pregnancy over time suggest rising awareness of FAS. Cessation is associated with
recidivism after pregnancy but also with reduced long-term drinking.
Interventions should target alcohol abstinence in pregnancy, but extend into the
puerperium.
PMID- 27610938
TI - Covert contrast and covert errors in persistent velar fronting.
AB - Acoustic and articulatory studies demonstrate covert contrast in perceptually
neutralised phonemic contrasts in both typical children and children with speech
disorders. These covert contrasts are thought to be relatively common and
symptomatic of phonetic speech disorders. However, clinicians in the speech
therapy clinic have had no easy way of identifying this covertness. This study
uses ultrasound tongue imaging to compare tongue contours for /t/and /k/in seven
children with persistent velar fronting. We present a method of overlaying tongue
contours to identify covert contrast at the articulatory level. Results show that
all seven children, contrary to expectations, produced both /t/and /k/with near
identical tongue shapes showing no evidence of covert contrast. However, further
analysis of one of the participants showed highly variable tongue shapes for
/t/and /k/, including retroflex productions of both. Although not phonologically
conditioned, this covert error is evidence of speech disorder at the phonetic
level.
PMID- 27610939
TI - Merging Visible Light Photoredox and Gold Catalysis.
AB - Since the beginning of this century, pi-Lewis acidic gold complexes have become
the catalysts of choice for a wide range of organic reactions, especially those
involving nucleophilic addition to carbon-carbon multiple bonds. For the most
part, however, the gold catalyst does not change oxidation state during the
course of these processes and two-electron redox cycles of the kind implicated in
cross-coupling chemistry are not easily accessible. In order to address this
limitation and expand the scope of gold catalysis beyond conventional
hydrofunctionalization, extensive efforts have been made to develop new oxidative
reactions using strong external oxidants capable of overcoming the high potential
of the AuI/AuIII redox couple. However, these processes typically require
superstoichiometric amounts of the oxidant and proceed under relatively harsh
conditions. Moreover, to date, gold-catalyzed oxidative coupling reactions have
remained somewhat limited in scope because, for many systems, the desired cross
coupling does not favorably compete with homodimerization or conventional
hydrofunctionalization. In 2013, we disclosed a new concept for gold-catalyzed
coupling reactions that, rather than involving external oxidants, employs aryl
radicals that act as both the oxidant and the coupling partner in overall redox
neutral transformations. For this, we developed a dual catalytic system combining
homogeneous gold catalysis with the emerging field of visible light photoredox
catalysis. Using aryldiazonium salts, which are known to act as sources of aryl
radicals upon activation with reducing photocatalysts, we could achieve
intramolecular oxy- and aminoarylations of alkenes upon irradiating the reaction
mixtures with visible light. Further studies on this transformation, in which
nucleophilic addition onto a gold-activated alkene is followed by C(sp3)-C(sp2)
bond formation, expanded the scope of the process to intermolecular, three
component oxyarylation, while inexpensive organic dyes and user-friendly
diaryliodonium salts could be employed as alternative photocatalysts and aryl
radical sources, respectively. The potential of dual gold/photoredox catalysis
was quickly realized by several research groups and a range of diverse new
coupling reactions involving nucleophilic addition to pi-systems and even P-H and
C(sp)-H functionalization have been developed. In addition to the ambient
reaction conditions and the simple setup using household light sources or even
sunlight, a key advantage of dual gold/photoredox catalysis results from the
simultaneous oxidation of gold(I) and coordination of the coupling partner, which
results in high levels of selectivity for the cross-coupled products over
homodimers. Furthermore, when gold complexes that are not catalytically active
prior to oxidation by the aryl radical are employed, background reactions not
involving coupling can be suppressed. Notably, this feature has allowed for the
successful use of allenes and alkynes, for which conventional
hydrofunctionalization pathways are highly favored, opening the door to new
transformations involving the most common substrate classes for gold catalysis.
In this Account, we provide an overview of dual gold/photoredox catalysis and
highlight the potential of this concept to greatly expand the scope of
homogeneous gold catalysis and enable the efficient construction of complex
organic molecules. Moreover, recent studies on the visible light-promoted
synthesis of novel gold(III) complexes suggest that photoredox activation could
yet find further applications in gold chemistry beyond coupling.
PMID- 27610937
TI - Inability to access health and social services associated with mental health
among people who inject drugs in a Canadian setting.
AB - BACKGROUND: People who inject drugs (PWID) face barriers to healthcare due to
reasons including comorbidity. We evaluated access to health and social services
by three of the most prevalent comorbid conditions among PWID: HIV, hepatitis C
(HCV), and mental health, in an urban setting in Canada. METHODS: Data were
derived from prospective cohorts of community-recruited PWID between 2005 and
2015. HIV and HCV serostatuses were based on antibody tests, while mental health
conditions and inability to access health and social services (barriers to
access) were determined by participants' self-report. We employed generalized
linear mixed models controlling for confounders to examine associations between
health conditions and barriers to access. RESULTS: Among 2494 participants, 1632
(65.4%) reported barriers to access at least once over a median of seven (IQR: 3,
12) semi-annual assessments. Mental health conditions were independently
associated with increased odds of reporting barriers (adjusted Odds Ratio (aOR):
1.45, 95% Confidence Interval (CI): 1.32, 1.58), while HIV was not (aOR: 0.96,
95% CI: 0.85, 1.08), and HCV was associated with decreased odds (aOR: 0.80, 95%
CI: 0.69, 0.93). The associations between mental health conditions and barriers
to access were consistent among PWID without HIV/HCV (aOR: 1.35, 95% CI: 1.10,
1.65), with HCV mono-infection (aOR: 1.55, 95% CI: 1.37, 1.75), and HCV/HIV co
infection (aOR: 1.36, 95% CI: 1.15, 1.60). CONCLUSIONS: Targeted strategies to
seek and treat mental health conditions in settings that serve PWID, and assist
PWID with mental health conditions in navigating healthcare system may improve
the publicly-funded health and social services.
PMID- 27610940
TI - High incidence of ventricular arrhythmias in patients with left ventricular
enlargement and moderate left ventricular dysfunction.
AB - BACKGROUND: Left ventricular ejection fraction (LVEF) <=35% is the cutoff value
used to identify patients at high risk of sudden cardiac death. However, whether
patients who have moderate left ventricular dysfunction and left ventricular
enlargement (LVE) have a high risk of ventricular arrhythmias (VAs) and cardiac
death is unclear. HYPOTHESIS: Patients with moderate left ventricular dysfunction
and LVE may have a high risk of VAs. METHODS: This study retrospectively analyzed
the data of 853 patients who have an implantable cardioverter
defibrillator/cardiac resynchronization therapy cardioverter-defibrillator
equipped with home monitoring. The patients were divided into 4 groups: group A,
35% < LVEF <= 45% and left ventricular end-diastolic dimension (LVEDD) >=60 mm;
group B, LVEF <=35% and LVEDD <60 mm; group C, 35% < LVEF <= 45% and LVEDD <60
mm; and group D, LVEF <=35% and LVEDD >=60 mm. RESULTS: During a mean follow-up
period of 30 +/- 13 months, 324 patients (38%) experienced VAs and 125 patients
(14.7%) experienced cardiac death. Based on multivariate Cox regression modeling,
group A had an increased risk of VAs (A vs B, hazard ratio [HR]: 1.563, 95%
confidence interval [CI]: 1.029-2.375, P = 0.036; A vs C, HR: 1.661, 95% CI:
1.204-2.294, P = 0.002) and cardiac death (A vs B, HR: 1.845, 95% CI: 1.013
3.356; A vs C, HR: 2.041, 95% CI: 1.136-3.731, P = 0.021). CONCLUSIONS: Patients
with moderate left ventricular dysfunction and LVE have a high risk of VAs and
cardiac death.
PMID- 27610941
TI - Genome-wide association study for semen traits of the bulls in Chinese Holstein.
AB - A genome-wide association study (GWAS) was performed to identify markers and
candidate genes for five semen traits in the Holstein bull population in China.
The analyzed dataset consisted of records from 692 bulls from eight bull
stations; each bull was genotyped using the Illumina BovineSNP50 BeadChip.
Association tests between each trait and the 41 188 informative high-quality SNPs
were achieved with gapit software. In total, 19 suggestive significant SNPs,
partly located within the reported QTL regions or within or close to the reported
candidate genes, associated with five semen traits were detected. By combining
our GWAS results with the biological functions of these genes, eight novel
promising candidate genes, including ETNK1, PDE3A, PDGFRB, CSF1R, WT1, DSCAML1,
SOD1 and RUNX2, were identified that potentially relate to semen traits. Our
findings may provide a basis for further research on the genetic mechanism of
semen traits and marker-assisted selection of such traits in Holstein bulls.
PMID- 27610942
TI - Sociocognitive factors and perceived consequences associated with alternative
forms of alcohol use.
AB - OBJECTIVE: Popular media have highly publicized alternative forms of alcohol use
(eg, eyeballing, inhaling alcohol vapor) among college students as a growing
concern, possibly associated with severe health risks. Formative research
indicates rarity of use. PARTICIPANTS AND METHODS: College students (Study 1: n =
411; Study 2: n = 687) completed an online survey. RESULTS: Findings confirmed
infrequent use of alternative methods of alcohol use and low likelihood of trying
them in the future (Study 1). Participants indicated varied reasons for possibly
trying each alternative form of alcohol use, but consistently perceived
consequences for all forms (ie, health concerns), as well as very low perceived
approval from close friends (Study 2). Social and environmental contextual
factors associated with possible use were also explored. CONCLUSIONS: College
students in the current sample have low prevalence and future likelihood of
alternative forms of alcohol use. This information can be used by campus health
practitioners to promote accurate normative data for alternative forms of alcohol
use. However, with increased perceptions of approval and media presence, future
trends could change. Findings revealed important risk factors for these
potentially hazardous forms of alcohol use.
PMID- 27610943
TI - The formidable cluster: The challenge of personality disorders among hospitalized
patients.
PMID- 27610944
TI - Differentiating Closed Versus Open Spinal Dysraphisms on Fetal MRI.
AB - OBJECTIVE: The purpose of this study is to identify differences in findings
between open and closed spinal dysraphisms seen on fetal MR images. MATERIALS AND
METHODS: A single-institution retrospective analysis of fetal MR images for
spinal dysraphism was performed. Postnatal images and clinical and operative
reports were reviewed. RESULTS: Sixteen fetuses with postnatally confirmed closed
spinal dysraphisms were included. Of these, 25% (4/16) had posterior fossa
anomalies, 12.5% (2/16) had ventriculomegaly, and 37.5% (6/16) had OEIS
(omphalocele, exstrophy, imperforate anus, and spinal defects) complex. Of 90
fetuses with postnatally confirmed open spinal dysraphism, 95.6% (86/90) had
posterior fossa anomalies, 85.6% (77/90) had ventriculomegaly, and none had OEIS
complex. Twenty fetuses with open spinal dysraphism were randomly selected to
compare with fetuses with closed spinal dysraphisms. Continuity of the epidermal
and subcutaneous tissues with the sac wall on fetal MR images was seen in 93.8%
(15/16) of patients with closed spinal dysraphisms, as opposed to 5% (1/20) of
patients with open spinal dysraphisms. The mean (+/- SD) sac wall thickness was
less in open (0.7 +/- 0.6 mm) than closed (2.9 +/- 1.3 mm; p < 0.001) spinal
dysraphism. None of the fetuses had T1-hyperintense fat within the defect.
CONCLUSION: On fetal MR images, closed spinal dysraphisms tend to have a sac wall
in continuity with the epidermal and subcutaneous tissues, a thicker sac wall,
fewer posterior fossa anomalies, and high association with OEIS complex.
PMID- 27610945
TI - Statin withdrawal in people with dementia.
AB - BACKGROUND: There are approximately 24 million people worldwide with dementia;
this is likely to increase to 81 million by 2040. Dementia is a progressive
condition, and usually leads to death eight to ten years after first symptoms.
End-of-life care should emphasise treatments that optimise quality of life and
physicians should minimise unnecessary or non-beneficial interventions. Statins
are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors; they
have become the cornerstone of pharmacotherapy for the management of
hypercholesterolaemia but their ability to provide benefit is unclear in the last
weeks or months of life. Withdrawal of statins may improve quality of life in
people with advanced dementia, as they will not be subjected to unnecessary
polypharmacy or side effects. However, they may help to prevent further vascular
events in people of advanced age who are at high risk of such events. OBJECTIVES:
To evaluate the effects of withdrawal or continuation of statins in people with
dementia on: cognitive outcomes, adverse events, behavioural and functional
outcomes, mortality, quality of life, vascular morbidity, and healthcare costs.
SEARCH METHODS: We searched ALOIS (medicine.ox.ac.uk/alois/), the Cochrane
Dementia and Cognitive Improvement Group Specialised Register on 11 February
2016. We also ran additional searches in MEDLINE, EMBASE, PsycINFO, CINAHL,
Clinical.Trials.gov and the WHO Portal/ICTRP on 11 February 2016, to ensure that
the searches were as comprehensive and as up-to-date as possible. SELECTION
CRITERIA: We included all randomised, controlled clinical trials with either a
placebo or 'no treatment' control group. We applied no language restrictions.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether
potentially relevant studies met the inclusion criteria, using standard
methodological procedures expected by Cochrane. We found no studies suitable for
inclusion therefore analysed no data. MAIN RESULTS: The search strategy
identified 28 unique references, all of which were excluded. AUTHORS'
CONCLUSIONS: We found no evidence to enable us to make an informed decision about
statin withdrawal in dementia. Randomised controlled studies need to be conducted
to assess cognitive and other effects of statins in participants with dementia,
especially when the disease is advanced.
PMID- 27610946
TI - Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with
Testicular Tissues.
AB - The role of monogenic mutations in the development of 46,XX
testicular/ovotesticular disorders of sex development (DSD) remains speculative.
Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX
ovarian insufficiency, such mutations have not been implicated in testicular
development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two
unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The
p.Arg92Trp mutation was absent from the clinically normal mothers and from 200
unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably
pathogenic. In vitro assays demonstrated that compared with wild-type NR5A1, the
mutant protein was less sensitive to NR0B1-induced suppression on the SOX9
enhancer element. Other sequence variants found in the patients were unlikely to
be associated with the phenotype. The results raise the possibility that specific
mutations in NR5A1 underlie testicular development in genetic females.
PMID- 27610948
TI - Interventricular conduction disorders after orthotopic heart transplantation:
risk factors and clinical relevance.
AB - BACKGROUND: Causes and significance of interventricular conduction disorders
(IVCDs) after orthotopic heart transplantation (OHT) are still unknown. METHODS:
We retrospectively researched the presence of IVCDs in 240 patients who underwent
bicaval OHT in three time periods: at day 1, after 1 year, and after 3 years from
OHT. To evaluate the impact of the surgical technique, a control population
treated with biatrial anastomosis was used. RESULTS: The most common IVCD was
right bundle branch block (RBBB). Its presence at day 1 correlated with
transpulmonary gradient before OHT. Its presence after 1 year and its development
correlated with a 1-month acute rejection score>=2 (p = .050 and p = .006). The
incidence of RBBB was higher in the biatrial control population (40.7% vs 23.8%,
p < .001). CONCLUSIONS: RBBB is the most common IVCD. Its presence can be
explained by a susceptibility of the right branch to heart positioning, pressure
overload, and acute rejection. IVCDs do not affect prognosis.
PMID- 27610949
TI - Fusing Porphyrins and Phospholes: Synthesis and Analysis of a Phosphorus
Containing Porphyrin.
AB - A phosphole-fused porphyrin dimer, as a representative of a new class of
porphyrins with a phosphorus atom, was synthesized for the first time. The
porphyrin dimer exhibits remarkably broadened absorption, indicating effective pi
conjugation over the two porphyrins through the phosphole moiety. The porphyrin
dimer possesses excellent electron-accepting character, which is comparable to
that of a representative electron-accepting material, [60]PCBM. These results
provide access to a new class of phosphorus-containing porphyrins with unique
optoelectronic properties.
PMID- 27610947
TI - Characterization of immunogenic Neu5Gc in bioprosthetic heart valves.
AB - BACKGROUND: The two common sialic acids (Sias) in mammals are N-acetylneuraminic
acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc).
Unlike most mammals, humans cannot synthesize Neu5Gc that is considered foreign
and recognized by circulating antibodies. Thus, Neu5Gc is a potential xenogenic
carbohydrate antigen in bioprosthetic heart valves (BHV) that tend to deteriorate
in time within human patients. METHODS: We investigated Neu5Gc expression in non
engineered animal-derived cardiac tissues and in clinically used commercial BHV,
and evaluated Neu5Gc immunogenicity on BHV through recognition by human anti
Neu5Gc IgG. RESULTS: Neu5Gc was detected by immunohistochemistry in porcine
aortic valves and in porcine and bovine pericardium. Qualitative analysis of Sia
linkages revealed Siaalpha2-3>Siaalpha2-6 on porcine/bovine pericardium while the
opposite in porcine aortic/pulmonary valve cusps. Similarly, six commercial BHV
containing either porcine aortic valve or porcine/bovine/equine pericardium
revealed Siaalpha2-3>Siaalpha2-6 expression. Quantitative analysis of Sia by HPLC
showed porcine/bovine pericardium express 4-fold higher Neu5Gc levels compared to
the porcine aortic/pulmonary valves, with Neu5Ac at 6-fold over Neu5Gc. Likewise,
Neu5Gc was expressed on commercial BHV (186.3+/-16.9 pmol Sia/MUg protein), with
Neu5Ac at 8-fold over Neu5Gc. Affinity-purified human anti-Neu5Gc IgG showing
high specificity toward Neu5Gc-glycans (with no binding to Neu5Ac-glycans) on a
glycan microarray, strongly bound to all tested commercial BHV, demonstrating
Neu5Gc immune recognition in cardiac xenografts. CONCLUSIONS: We conclusively
demonstrated Neu5Gc expression in native cardiac tissues, as well as in six
commercial BHV. These Neu5Gc xeno-antigens were recognized by human anti-Neu5Gc
IgG, supporting their immunogenicity. Altogether, these findings suggest BHV
Neu5Gc/anti-Neu5Gc may play a role in valve deterioration warranting further
investigation.
PMID- 27610951
TI - Oro-nasal myiasis in a lymphoma patient.
PMID- 27610950
TI - Stable isotope tracers and exercise physiology: past, present and future.
AB - Stable isotope tracers have been invaluable assets in physiological research for
over 80 years. The application of substrate-specific stable isotope tracers has
permitted exquisite insight into amino acid, fatty-acid and carbohydrate
metabolic regulation (i.e. incorporation, flux, and oxidation, in a tissue
specific and whole-body fashion) in health, disease and response to acute and
chronic exercise. Yet, despite many breakthroughs, there are limitations to
'substrate-specific' stable isotope tracers, which limit physiological insight,
e.g. the need for intravenous infusions and restriction to short-term studies
(hours) in controlled laboratory settings. In recent years significant interest
has developed in alternative stable isotope tracer techniques that overcome these
limitations, in particular deuterium oxide (D2 O or heavy water). The unique
properties of this tracer mean that through oral administration, the turnover and
flux through a number of different substrates (muscle proteins, lipids, glucose,
DNA (satellite cells)) can be monitored simultaneously and flexibly
(hours/weeks/months) without the need for restrictive experimental control. This
makes it uniquely suited for the study of 'real world' human exercise physiology
(amongst many other applications). Moreover, using D2 O permits evaluation of
turnover of plasma and muscle proteins (e.g. dynamic proteomics) in addition to
metabolomics (e.g. fluxomics) to seek molecular underpinnings, e.g. of exercise
adaptation. Here, we provide insight into the role of stable isotope tracers,
from substrate-specific to novel D2 O approaches, in facilitating our
understanding of metabolism. Further novel potential applications of stable
isotope tracers are also discussed in the context of integration with the
snowballing field of 'omic' technologies.
PMID- 27610953
TI - Deployment-Related Benefit Finding and Postdeployment Marital Satisfaction in
Military Couples.
AB - Extensive research has evaluated potential negative effects of military
deployments on romantic relationships. Comparatively few studies have examined
potential positive effects of such deployments. In stressful situations, benefit
finding (BF) has been found to be linked with better functioning on both
individual and interpersonal levels. This study reports on deployment-related BF
in a sample of 67 male service members (SMs) who deployed at least once since
9/11/2001 and their wives. Couples completed measures of marital satisfaction at
baseline (an average of 1 year postdeployment) and follow-up 4-6 months later. At
follow-up, SMs also provided data on symptoms of posttraumatic stress, and both
partners provided reports of deployment-related BF. Multivariate path analysis
controlling for SMs' PTSD symptom severity revealed that wives' BF was positively
associated with increases in SMs' relationship satisfaction. These findings
suggest that wives' responses to deployment may be more influential than SMs'
responses to deployment on military couples' relationships. This pattern
indicates that support for spouses during deployments is essential; furthermore,
such support should include an emphasis on trying to facilitate personal growth
in spouses.
PMID- 27610952
TI - The effect of acute weight restoration on dietary fat preference in hospitalized
patients with anorexia nervosa.
AB - OBJECTIVE: Individuals with anorexia nervosa (AN) restrict fat intake. The
Geiselman Food Preference Questionnaire-I(c) (FPQ) is a validated self-report
instrument that yields a fat preference score (>100 = high fat preference, <100 =
low fat preference). The goal of the study was to assess the utility of the FPQ
in patients with AN. SPECIFIC AIMS: (1) to examine change in fat preference
scores before and after weight restoration in hospitalized patients; and (2) to
compare patients' scores before and after weight restoration to scores from
healthy participants (HPs). METHOD: The FPQ was completed by 88 patients and 115
HPs. RESULTS: Compared with HPs, patients had significantly lower fat preference
scores before (74.03 +/- 32.03 vs. 102.93 +/- 16.89, P < 0.001) and after (81.51
+/- 26.89 vs. 102.92 +/- 16.89, P < 0.001) weight restoration. Fat preference
scores increased with weight gain (74.03 + 32.03 vs. 81.51 + 26.89, P < 0.01) but
did not normalize in AN. DISCUSSION: Acutely weight restored patients continue to
endorse decreased preference for high fat foods. The FPQ may be a useful metric
by which to assess improvements in diet during treatment. Further study is
warranted to validate the FPQ against observed food intake in AN. (c) 2016 Wiley
Periodicals, Inc.(Int J Eat Disord 2017; 50:148-151).
PMID- 27610954
TI - Perichromosomal protein Ki67 supports mitotic chromosome architecture.
AB - Although the condensin complexes and topoisomerase IIalpha (TopoIIalpha) are the
central players in mitotic chromosome formation, they are insufficient for its
completion, and additional factors involved in the process have been extensively
sought. In this study, we examined the possibility that Ki67, a perichromosomal
protein widely used as a cell proliferation marker, is one such factor. Using a
combination of auxin-inducible degron and CRISPR-Cas9-based gene editing
technologies, we generated a human HCT116 cell line in which Ki67 is rapidly
depleted in a few hours. The removal of Ki67 before mitotic entry did not impact
the early mitotic chromosome assembly observed in prophase but subsequently
resulted in the formation of misshapen mitotic chromosomes. When Ki67 was removed
after mitotic entry, preassembled rod-shaped mitotic chromosomes became
disorganized. In addition, we show that Ki67 and TopoIIalpha are reciprocally
coimmunoprecipitated from mitotic cell extracts. These observations indicate that
Ki67 aids the finalization of mitotic chromosome formation and helps maintain rod
shaped chromosome architecture, likely in collaboration with TopoIIalpha.
Together, these findings represent a new model in which mitotic chromosome
architecture is supported both internally and externally.
PMID- 27610955
TI - Significant reduction of inflammation and sebaceous glands size in acne vulgaris
lesions after intense pulsed light treatment.
AB - Intense pulsed light (IPL) has been used for years in treatment of acne vulgaris.
However, quantitative evaluation of histopathological changes after its use as a
sole therapy was poorly investigated. Accordingly, this study aims to objectively
evaluate inflammatory infiltrate and sebaceous glands in acne vulgaris after IPL.
Twenty-four patients of acne were treated with six IPL sessions. Clinical
evaluation was done at 2 weeks after last session by counting acne lesions.
Patient satisfaction using Cardiff Acne Disability Index (CADI) was recorded at
baseline, 2 weeks and 3 months after IPL. Using histopathological and
computerized morphometric analysis, quantitative evaluation of inflammatory
infiltrate and measurement of surface area of sebaceous glands were performed for
skin biopsies at baseline and 2 weeks after last session. After IPL, there was
significant reduction of all acne lesions especially inflammatory variety with
significant decrease of CADI score at 2 weeks and 3 months after IPL (p < .05).
Microscopically, there was significant decrease in density of inflammatory
infiltrate and surface area of sebaceous glands (p < .05). So, IPL is fairly
effective therapy in acne vulgaris especially inflammatory variety. The results
suggest that IPL could improve acne lesions through targeting both inflammation
and sebaceous glands.
PMID- 27611006
TI - Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An
Aspect of the Hygiene/Missing Old Friends Hypothesis.
AB - BACKGROUND: We here study antibodies against phosphorylcholine (anti-PC) which we
reported to be inversely associated with atherosclerosis, cardiovascular disease
(CVD), and autoimmune conditions. In previous studies, we determined that this
inverse association is more pronounced at low levels with high risk and at high
levels, with decreased risk. We compare individuals from Kitava, New Guinea (with
low risk of these conditions), with Swedish controls. METHODS: We studied a group
of 178 individuals from Kitava (age 20-86), and compared those above age 40 (n =
108) with a group of age- and sex-matched individuals from a population based
cohort in Sweden (n = 108). Traditional risk factors for CVD and fatty acids were
determined. IgM, IgG, and IgA anti-PC were tested by enzyme-linked immunosorbent
assay (ELISA). RESULTS: All anti-PC measures were significantly lower among
Swedish controls as compared to Kitavans (p < 0.001), independent of traditional
risk factors. Having low levels of anti-PC, defined as below 25th percentile of
values among Swedish controls, was associated with this cohort after adjustment
for other risk factors (OR 5.7, 95% CI 2.2-14.7 for IgM; OR 31.7, 95% CI 3.9-252
for IgA; and OR 11.1, 95% CI 2.4-51 for IgG). CONCLUSIONS: PC is highly exposed
on microorganisms and helminths (common on Kitava) exposing much PC which humans
and hominids may have been exposed to for millions of years. We propose that low
anti-PC levels in the developed world could be a new aspect of the hygiene
hypothesis, generating a pro-inflammatory and pro-atherosclerotic state.
PMID- 27611007
TI - Highly Controlled Codeposition Rate of Organolead Halide Perovskite by Laser
Evaporation Method.
AB - Organolead-halide perovskites can be promising materials for next-generation
solar cells because of its high power conversion efficiency. The method of
precise fabrication is required because both solution-process and vacuum-process
fabrication of the perovskite have problems of controllability and
reproducibility. Vacuum deposition process was expected to achieve precise
control; however, vaporization of amine compound significantly degrades the
controllability of deposition rate. Here we achieved the reduction of the
vaporization by implementing the laser evaporation system for the codeposition of
perovskite. Locally irradiated continuous-wave lasers on the source materials
realized the reduced vaporization of CH3NH3I. The deposition rate was stabilized
for several hours by adjusting the duty ratio of modulated laser based on
proportional-integral control. Organic-photovoltaic-type perovskite solar cells
were fabricated by codeposition of PbI2 and CH3NH3I. A power-conversion
efficiency of 16.0% with reduced hysteresis was achieved.
PMID- 27611008
TI - Comparisons of regular and on-demand regimen of PED5-Is in the treatment of ED
after nerve-sparing radical prostatectomy for Prostate Cancer.
AB - Phosphodiesterase type-5 inhibitors (PDE5-Is) have been recommended as first line
therapy for erectile dysfunction for patients received nerve-sparing radical
prostatectomy for prostate cancer. We examed the efficiency of PDE5-Is and
considered the optimal application. Systematic search of PubMed, Embase and the
Cochrane Library was performed to identify all the studies. We identified 103
studies including 3175 patients, of which 14 were recruited for systematic
review. Compared with placebo, PDE5-Is significantly ameliorated the
International Index of Erectile Function-Erectile Function domain score (IIEF)
scores (MD 4.89, 95% CI 4.25-5.53, p < 0.001). By network meta-analysis,
sildenafil seems to be the most efficiency with a slightly higher rate of
treatment-emergent adverse events (TEATs), whereas tadalafil had the lowest
TEATs. In terms of IIEF scores, regular regimen was remarkably better than on
demand (MD 3.28, 95% CI 1.67-4.89, p < 0.001). Regular use was not associated
with higher proportion of patients suffering TEATs compared with on-demand (RR
1.02, 95% CI 0.90-1.16, p = 0.72). Compared with placebo, PDE5-Is manifested
significantly improved treatment outcomes. Overall, regular regimen demonstrated
statistically pronounced better potency than on-demand. Coupled with the
comparable rate of side effects, these findings support the regular delivery
procedure to be a cost-effective option for patients.
PMID- 27611009
TI - miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation
by primary macrophages and dendritic cells.
AB - Antigen uptake, processing and presentation by antigen presenting cells (APCs)
are tightly coupled processes which consequently lead to the activation of innate
and adaptive immune responses. However, the regulatory role of microRNA (miRNAs)
in these critical pathways is poorly understood. In this study, we show that
overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing
of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic
cells. MiRNA mimic transfected APCs exhibit defects in antigen presentation (Ova
and CMV antigen) to CD4+ T-cells leading to reduced cell proliferation. Using
transgenic OT-II mice we demonstrated that this impairment in T-cell
proliferation is specific to antigen provided i.e., Ova. Further, human T-cells
co-cultured with miRNA transfected dendritic cells secrete low levels of T helper
(Th)-1 polarization associated cytokines. Analysis of molecules regulating APC
and T-cell receptor interaction shows miRNA-mediated induced expression of
Programmed Death-Ligand 1 (PD-L1) which inhibits T-cell proliferation. Blocking
PD-L1 with antibodies rescues miRNA-mediated inhibition of T cell priming by DCs.
These results uncover regulatory functions of miR-24, miR-30b and miR-142-3p in
pairing innate and adaptive components of immunity.
PMID- 27611011
TI - An unrestricted diet for uncomplicated diverticulitis is safe: results of a
prospective diverticulitis diet study.
AB - AIM: The optimal diet for uncomplicated diverticulitis is unclear. Guidelines
refrain from recommendation due to lack of objective information. The aim of the
study was to determine whether an unrestricted diet during a first acute episode
of uncomplicated diverticulitis is safe. METHOD: A prospective cohort study was
performed of patients diagnosed with diverticulitis for the first time between
2012 and 2014. Requirements for inclusion were radiologically proven modified
Hinchey Ia/b diverticulitis, American Society of Anesthesiologists class I-III
and the ability to tolerate an unrestricted diet. Exclusion criteria were the use
of antibiotics and suspicion of inflammatory bowel disease or malignancy. All
included patients were advised to take an unrestricted diet. The primary outcome
parameter was morbidity. Secondary outcome measures were the development of
recurrence and ongoing symptoms. RESULTS: There were 86 patients including 37
(43.0%) men. All patients were confirmed to have taken an unrestricted diet.
There were nine adverse events in seven patients. These consisted of readmission
for pain (five), recurrent diverticulitis (one) and surgery (three) for ongoing
symptoms (two) and Hinchey Stage III (one). Seventeen (19.8%) patients
experienced continuing symptoms 6 months after the initial episode and 4 (4.7%)
experienced recurrent diverticulitis. CONCLUSION: The incidence of complications
among patients taking an unrestricted diet during an initial acute uncomplicated
episode of diverticulitis was in line with that reported in the literature.
PMID- 27611010
TI - Partial splenic embolization to permit continuation of systemic chemotherapy.
AB - Systemic chemotherapy treatments, commonly those that comprise oxaliplatin, have
been linked to the appearance of distinctive liver lesions that evolves to portal
hypertension, spleen enlargement, platelets sequestration, and thrombocytopenia.
This outcome can interrupt treatment or force dosage reduction, decreasing
efficiency of cancer therapy. We conducted a prospective phase II study for the
evaluation of partial splenic embolization in patients with thrombocytopenia that
impeded systemic chemotherapy continuation. From August 2014 through July 2015,
33 patients underwent partial splenic embolization to increase platelets count
and allow their return to treatment. Primary endpoint was the accomplishment of a
thrombocyte level superior to 130 * 109 /L and the secondary endpoints were the
return to chemotherapy and toxicity. Partial splenic embolization was done 36
times in 33 patients. All patients presented gastrointestinal cancer and
colorectal malignancy was the commonest primary site. An average of 6.4 cycles of
chemotherapy was done before splenic embolization and the most common regimen was
Folfox. Mean platelet count prior to embolization was 69 * 109 /L. A total of 94%
of patients achieved primary endpoint. All patients in need reinitiated treatment
and median time to chemotherapy return was 14 days. No grade 3 or above adverse
events were identified. Aiming for a 50% to 70% infarction area may be sufficient
to achieve success without the complications associated with more extensive
infarction. Combined with the better safety profile, partial splenic embolization
is an excellent option in the management of thrombocytopenia, enabling the
resumption of systemic chemotherapy with minimal procedure-related morbidity.
PMID- 27611012
TI - Intestinal dysfunction in Parkinson's disease: Lessons learned from translational
studies and experimental models.
AB - BACKGROUND: Symptoms of digestive dysfunction in patients with Parkinson's
disease (PD) occur at all stages of the disease, often preceding the onset of
central motor symptoms. On the basis of these PD-preceding symptoms it has been
proposed that PD could initiate in the gut, and that the presence of alpha
synuclein aggregates, or Lewy bodies in the enteric nervous system might
represent one of the earliest signs of the disease. Following this hypothesis,
much research has been focused on the digestive tract to unravel the mechanisms
underlying the onset and progression of PD, with particular attention to the role
of alterations in enteric neurotransmission in the pathophysiology of intestinal
motility disturbances. There is also evidence suggesting that the development of
central nigrostriatal neurodegeneration is associated with the occurrence of gut
inflammation, characterized by increments of tissue pro-inflammatory markers and
oxidative stress, which might support conditions of bowel neuromotor
abnormalities. PURPOSE: The present review intends to provide an integrated and
critical appraisal of the available knowledge on the alterations of enteric
neuromuscular pathways regulating gut motor activity both in humans and
preclinical models of PD. Moreover, we will discuss the possible involvement of
neuro-immune mechanisms in the pathophysiology of aberrant gastrointestinal gut
transit and neuromuscular activity in the small and large bowel.
PMID- 27611013
TI - New insights about time-varying diffusivity and its estimation from diffusion
MRI.
AB - PURPOSE: Characterizing the relation between the applied gradient sequences and
the measured diffusion MRI signal is important for estimating the time-dependent
diffusivity, which provides important information about the microscopic tissue
structure. THEORY AND METHODS: In this article, we extend the classical theory of
Stepisnik for measuring time-dependent diffusivity under the Gaussian phase
approximation. In particular, we derive three novel expressions which represent
the diffusion MRI signal in terms of the mean-squared displacement, the
instantaneous diffusivity, and the velocity autocorrelation function. We present
the explicit signal expressions for the case of single diffusion encoding and
oscillating gradient spin-echo sequences. Additionally, we also propose three
different models to represent time-varying diffusivity and test them using Monte
Carlo simulations and in vivo human brain data. RESULTS: The time-varying
diffusivities are able to distinguish the synthetic structures in the Monte-Carlo
simulations. There is also strong statistical evidence about time-varying
diffusivity from the in vivo human data set. CONCLUSION: The proposed theory
provides new insights into our understanding of the time-varying diffusivity
using different gradient sequences. The proposed models for representing time
varying diffusivity can be utilized to study time-varying diffusivity using in
vivo human brain diffusion MRI data. Magn Reson Med 78:763-774, 2017. (c) 2016
International Society for Magnetic Resonance in Medicine.
PMID- 27611014
TI - A systems biology approach reveals major metabolic changes in the
thermoacidophilic archaeon Sulfolobus solfataricus in response to the carbon
source L-fucose versus D-glucose.
AB - Archaea are characterised by a complex metabolism with many unique enzymes that
differ from their bacterial and eukaryotic counterparts. The thermoacidophilic
archaeon Sulfolobus solfataricus is known for its metabolic versatility and is
able to utilize a great variety of different carbon sources. However, the
underlying degradation pathways and their regulation are often unknown. In this
work, the growth on different carbon sources was analysed, using an integrated
systems biology approach. The comparison of growth on L-fucose and D-glucose
allows first insights into the genome-wide changes in response to the two carbon
sources and revealed a new pathway for L-fucose degradation in S. solfataricus.
During growth on L-fucose major changes in the central carbon metabolic network,
as well as an increased activity of the glyoxylate bypass and the 3
hydroxypropionate/4-hydroxybutyrate cycle were observed. Within the newly
discovered pathway for L-fucose degradation the following key reactions were
identified: (i) L-fucose oxidation to L-fuconate via a dehydrogenase, (ii)
dehydration to 2-keto-3-deoxy-L-fuconate via dehydratase, (iii) 2-keto-3-deoxy-L
fuconate cleavage to pyruvate and L-lactaldehyde via aldolase and (iv) L
lactaldehyde conversion to L-lactate via aldehyde dehydrogenase. This pathway as
well as L-fucose transport shows interesting overlaps to the D-arabinose pathway,
representing another example for pathway promiscuity in Sulfolobus species.
PMID- 27611015
TI - Functional Reconstitution of a Fungal Natural Product Gene Cluster by Advanced
Genome Editing.
AB - Filamentous fungi produce varieties of natural products even in a strain
dependent manner. However, the genetic basis of chemical speciation between
strains is still widely unknown. One example is trypacidin, a natural product of
the opportunistic human pathogen Aspergillus fumigatus, which is not produced
among different isolates. Combining computational analysis with targeted gene
editing, we could link a single nucleotide insertion in the polyketide synthase
of the trypacidin biosynthetic pathway and reconstitute its production in a
nonproducing strain. Thus, we present a CRISPR/Cas9-based tool for advanced
molecular genetic studies in filamentous fungi, exploiting selectable markers
separated from the edited locus.
PMID- 27611016
TI - An Extremely Rare Disorder of Somatic Mosaicism: CLOVES Syndrome.
AB - BACKGROUND: CLOVES (Congenital Lipomatous Overgrowth, Vascular malformations,
Epidermal nevi Scoliosis, Skeletal, Spinal) syndrome is an extremely rare,
complex, non-Mendelian genetic condition with clinical overlap to several other
overgrowth syndromes. PURPOSE: This article shares an interesting case report of
the prenatal to postnatal diagnostic course for an infant with this condition.
CASE FINDINGS/RESULTS: It shares prenatal and postnatal images and imaging
studies which helped confirm the diagnosis. In addition, the unusual genetic
causes of the condition as well as recommended patient-specific management and
treatment therapies for this complex condition are discussed. IMPLICATIONS FOR
PRACTICE: Practice implications include honing of physical examination skills and
facilitating diagnostic testing required to differentiate CLOVES syndrome from
similar conditions. Providers must provide ongoing information and ensure support
to families during this diagnostic process. In addition, the majority of care
will likely be provided beyond the newborn period. As such, providers must
facilitate outpatient follow-up with a number of consultants after hospital
discharge. IMPLICATIONS FOR RESEARCH: Because CLOVES syndrome is so rare,
research in this area is limited to a small number of field experts. These
experts, however, are well-suited to continue research surrounding disease
management and lesion treatment (whether surgical, procedural, or medical) moving
forward.
PMID- 27611017
TI - Leptospermum Honey for Wound Care in an Extremely Premature Infant.
AB - BACKGROUND/INTRODUCTION TO CASE: Neonatal wound care is challenging due to the
fragility and vulnerable skin structure. Neonates are often left susceptible to
the forces of their environment, leaving them open to infection when skin injury
occurs. Leptospermum honey has been used successfully in adult patients, with
evidence lacking in the neonatal population. This case demonstrates the
management of a difficult-to-heal wound in a 23-week gestation infant. PURPOSE:
Selecting the proper treatment and products for wound healing is challenging,
with little evidence-based research available for the treatment of neonatal
wounds. Leptospermum honey and other adult-driven dressings have been used for
neonatal wound care as well as other adult-driven dressings. This case
demonstrates the benefits of Leptospermum honey as an option for neonatal wounds.
CASE FINDINGS/RESULTS: This case presents the treatment and healing of an
extensive wound of a 23-week gestation neonate using a hydrogel product initially
and then transitioning to a Leptospermum honey dressing due to suboptimal
healing. Results of this treatment included quick healing time, little to no
scarring, and no loss of movement or function to the affected extremities.
IMPLICATIONS FOR PRACTICE: The incorporation of Leptospermum honey for wound care
has the potential to promote faster wound healing, with less scarring in the
neonatal population. IMPLICATIONS FOR RESEARCH: Adult wound care principles have
been applied in the face of a weak evidence base relating to neonatal-specific
cases. There is a need for continued research related to moist wound healing in
the neonatal population, with resulting product and practice recommendations.
PMID- 27611020
TI - Infant Mortality Rates and Preterm Birth: A Challenge for Advocacy.
PMID- 27611018
TI - Comparison of Neonatal Abstinence Syndrome Manifestations in Preterm Versus Term
Opioid-Exposed Infants.
AB - BACKGROUND: Twenty percent to 40% of infants exposed to in utero opioid were
delivered preterm. There is currently no neonatal abstinence syndrome (NAS)
scoring tool known to accurately evaluate preterm opioid-exposed infants. This
can lead to difficulties in titrating pharmacotherapy in this population.
PURPOSE: To describe NAS symptoms in preterm opioid-exposed infants in comparison
with matched full-term controls. METHODS: This was a retrospective cohort study
from a single tertiary care center of methadone-exposed infants born between 2006
and 2010. Using modified Finnegan scale scores recorded every 3 to 4 hours
beginning at 6 hours of life until 24 to 48 hours after medication
discontinuation, NAS symptoms was compared between 45 preterm infants and 49 full
term matched controls. Concurrent neonatal medical diagnoses were also compared.
RESULTS: The median gestational age in the preterm group was 35 weeks
(interquartile range [IQR] = 33-36) versus 39 weeks (IQR = 38-40) in the term
group. Preterm infants scored less frequently for many items including sleep
disturbance (24.4% vs 46.2%), tremors (77.9% vs 89.7%), muscle tone (87.9% vs
97.4%), sweating (2.1% vs 9.4%), nasal stuffiness (11.9% vs 20.5%), and loose
stools (7.0% vs 14.3%) than full-term controls. Preterm infants scored more
frequently for hyperactive moro reflex (26.4% vs 5.5%), tachypnea (19.3% vs
16.1%), and poor feeding (24.6% vs 11.8%). IMPLICATIONS FOR PRACTICE: Provider
awareness of differences in manifestations of preterm and term infants with NAS,
as well as concurrent prematurity diagnoses that can influence NAS scoring, is
needed. These findings mandate the development of a modified NAS scoring tool for
the preterm NAS population. IMPLICATIONS FOR RESEARCH: A preterm NAS scoring tool
needs to be developed and validated to more accurately evaluate and treat preterm
opioid-exposed infants.
PMID- 27611021
TI - Promoting Breast Milk Nutrition in Infants With Cleft Lip and/or Palate.
AB - BACKGROUND: The orofacial defect of cleft lip/palate (CL/P) involves an altered
physiological anatomy that affects the infant's feeding ability. Infants have
cleft lip (CL), cleft palate (CP), or both (CL/P). Dysfunction in the seal, as
with cleft lip, or in the ability to coordinate muscle movement to generate
negative pressure, as with cleft palate, leads to feeding issues that may
compromise growth and affect bonding. PURPOSE: The purpose of this article is to
present (1) scientific evidence that supports clinical feeding practices for the
infant with CL/P and (2) teaching strategies for staff and parents. METHODS:
Evidence was synthesized using a narrative review of randomized controlled
trials, qualitative studies, systematic reviews, professional guidelines, and
position statements. Findings were used to present specialized equipment and
feeding techniques to support human milk feeding. FINDINGS: Special
considerations for feeding infants with CL/P include assessing the infant's
sucking ability, demonstrating proper breastfeeding positioning, supporting
mothers to establish and maintain their milk supply, considering adaptive feeding
equipment (ie, specialized bottles and nipples), and education about the benefits
of human milk. IMPLICATIONS FOR PRACTICE AND RESEARCH: Support from healthcare
professionals, particularly lactation specialists and nursing staff, is critical.
Breastfeeding and the use of human milk should be prioritized and supported.
Research is needed to explore environmental, genetic, and nutritional causes (eg,
folic acid deficiency) of orofacial defects.
PMID- 27611022
TI - Inhibitory Effect of Furanic and Phenolic Compounds on Exoelectrogenesis in a
Microbial Electrolysis Cell Bioanode.
AB - The objective of this study was to systematically investigate the inhibitory
effect of furfural (FF), 5-hydroxymethylfurfural (HMF), syringic acid (SA),
vanillic acid (VA), and 4-hydroxybenzoic acid (HBA), which are problematic
lignocellulose-derived byproducts, on exoelectrogenesis in the bioanode of a
microbial electrolysis cell. The five compound mixture at an initial total
concentration range from 0.8 to 8.0 g/L resulted in an up to 91% current decrease
as a result of exoelectrogenesis inhibition; fermentative, nonexoelectrogenic
biotransformation pathways of the five compounds were not affected. Furthermore,
the parent compounds at a high concentration, as opposed to their
biotransformation products, were responsible for the observed inhibition. All
five parent compounds contributed to the observed inhibition of the mixture. The
IC50 (i.e., concentration resulting in 50% current decrease) of individually
tested parent compounds was 2.7 g/L for FF, 3.0 g/L for HMF, 1.9 g/L for SA, 2.1
g/L for VA and 2.0 g/L for HBA. However, the parent compounds, when tested below
their respective noninhibitory concentration, jointly resulted in significant
inhibition as a mixture. Catechol and phenol, which were persistent
biotransformation products, inhibited exoelectrogenesis only at high
concentrations, but to a lesser extent than the parent compounds.
Exoelectrogenesis recovery from inhibition by all compounds was observed at
different rates, with the exception of catechol, which resulted in irreversible
inhibition.
PMID- 27611024
TI - Microscopic Image of Leishman-Donovan Bodies in Bone Marrow Aspirate Smear of
Patient Suffering from Unexplained Intermittent Low-Grade Fever and Cough.
PMID- 27611023
TI - Tillage practices and straw-returning methods affect topsoil bacterial community
and organic C under a rice-wheat cropping system in central China.
AB - The objective of this study was to investigate how the relationships between
bacterial communities and organic C (SOC) in topsoil (0-5 cm) are affected by
tillage practices [conventional intensive tillage (CT) or no-tillage (NT)] and
straw-returning methods [crop straw returning (S) or removal (NS)] under a rice
wheat rotation in central China. Soil bacterial communities were determined by
high-throughput sequencing technology. After two cycles of annual rice-wheat
rotation, compared with CT treatments, NT treatments generally had significantly
more bacterial genera and monounsaturated fatty acids/saturated fatty acids
(MUFA/STFA), but a decreased gram-positive bacteria/gram-negative bacteria ratio
(G(+)/G(-)). S treatments had significantly more bacterial genera and MUFA/STFA,
but had decreased G(+)/G(-) compared with NS treatments. Multivariate analysis
revealed that Gemmatimonas, Rudaea, Spingomonas, Pseudomonas, Dyella,
Burkholderia, Clostridium, Pseudolabrys, Arcicella and Bacillus were correlated
with SOC, and cellulolytic bacteria (Burkholderia, Pseudomonas, Clostridium,
Rudaea and Bacillus) and Gemmationas explained 55.3% and 12.4% of the variance in
SOC, respectively. Structural equation modeling further indicated that tillage
and residue managements affected SOC directly and indirectly through these
cellulolytic bacteria and Gemmationas. Our results suggest that Burkholderia,
Pseudomonas, Clostridium, Rudaea, Bacillus and Gemmationas help to regulate SOC
sequestration in topsoil under tillage and residue systems.
PMID- 27611025
TI - Type A aortic dissection with intimal intussusception.
PMID- 27611027
TI - In-situ pyrogenic production of biodiesel from swine fat.
AB - In-situ production of fatty acid methyl esters from swine fat via thermally
induced pseudo-catalytic transesterification on silica was investigated in this
study. Instead of methanol, dimethyl carbonate (DMC) was used as acyl acceptor to
achieve environmental benefits and economic viability. Thermo-gravimetric
analysis of swine fat reveals that swine fat contains 19.57wt.% of water and
impurities. Moreover, the fatty acid profiles obtained under various conditions
(extracted swine oil+methanol+NaOH, extracted swine oil+DMC+pseudo-catalytic, and
swine fat+DMC+pseudo-catalytic) were compared. These profiles were identical,
showing that the introduced in-situ transesterification is technically feasible.
This also suggests that in-situ pseudo-catalytic transesterification has a high
tolerance against impurities. This study also shows that FAME yield via in-situ
pseudo-catalytic transesterification of swine fat reached up to 97.2% at 380
degrees C. Therefore, in-situ pseudo-catalytic transesterification can be
applicable to biodiesel production of other oil-bearing biomass feedstocks.
PMID- 27611026
TI - High efficiency cell-recycle continuous sodium gluconate production by
Aspergillus niger using on-line physiological parameters association analysis to
regulate feed rate rationally.
AB - In this paper, a system of cell-recycle continuous fermentation for sodium
gluconate (SG) production by Aspergillus niger (A. niger) was established. Based
on initial continuous fermentation result (100.0h) with constant feed rate, an
automatic feedback strategy to regulate feed rate using on-line physiological
parameters (OUR and DO) was proposed and applied successfully for the first time
in the improved continuous fermentation (240.5h). Due to less auxiliary time,
highest SG production rate (31.05+/-0.29gL(-1)h(-1)) and highest yield (0.984+/
0.067molmol(-1)), overall SG production capacity (975.8+/-5.8gh(-1)) in 50-L
fermentor of improved continuous fermentation increased more than 300.0% compared
to that of batch fermentation. Improvement of mass transfer and dispersed mycelia
morphology were the two major reasons responsible for the high SG production
rate. This system had been successfully applied to industrial fermentation and SG
production was greatly improved.
PMID- 27611028
TI - Changes on structural properties of biomass pretreated by combined deacetylation
with liquid hot water and its effect on enzymatic hydrolysis.
AB - A novel combined pretreatment of deacetylation and liquid hot water (LHW) was
invented which has been proved to be effective in increasing enzymatic hydrolysis
yield of biomass. In order to further understand the effect of this new
pretreatment process on biomass, the variation on structural properties including
cellulose crystallinity index (CrI), specific surface area (SSA) and degree of
polymerization (DP) before/after pretreatment and how these properties affected
the enzymatic hydrolysis of biomass were explored. The improvement of
pretreatment severity (PS) could increase CrI, SSA and reduce DP. Whereas the
enhancement of degree of deacetylation could decrease SSA and DP. An optimal
formula (E12Y=0.347(100-CrI)(-0.375)*(SSA)(0.203)*(1700-DP)(0.281)) was achieved
to express the correlation between structural properties and enzymatic hydrolysis
after 12h. The enzymatic yield was more sensitive to CrI than to SSA and DP.
PMID- 27611029
TI - The enhancement of the hydrolysis of bamboo biomass in ionic liquid with chitosan
based solid acid catalysts immobilized with metal ions.
AB - Three kinds of sulfonated cross-linked chitosan (SCCR) immobilized with metal
ions of Cu(2+), Fe(3+) and Zn(2+) individually were synthesized and firstly used
as solid acid catalysts in the hydrolysis of bamboo biomass. FTIR spectra showed
that metal ions had been introduced into SCCR and the N-metal ions coordinate
bound was formed. The particle sizes of these catalysts were about 500-1000MUm
with a pore size of 50-160MUm. All of the three kinds of catalysts performed well
for bamboo hydrolysis with 1-butyl-3-methyl-imidazolium chloride used as solvent.
The most effective one was sulfonated cross-linked chitosan immobilized with
Fe(3+) (Fe(3+)-SCCR). TRS yields were up to 73.42% for hydrolysis of bamboo
powder in [C4mim]Cl with Fe(3+)-SCCR at 120 degrees C and 20RPM after 24h. These
novel chitosan-based metal ions immobilized solid acid catalysts with ionic
liquids as the solvent might be promising to facilitate cost-efficient conversion
of biomass into biofuels and bioproducts.
PMID- 27611030
TI - Flocculation properties of several microalgae and a cyanobacterium species during
ferric chloride, chitosan and alkaline flocculation.
AB - Flocculation holds great potential as a low-cost harvesting method for microalgae
biomass production. Three flocculation methods (ferric chloride, chitosan, and
alkaline flocculation) were compared in this study for the harvesting of 9
different freshwater and marine microalgae and one cyanobacterium species. Ferric
chloride resulted in a separation efficiency greater than 90% with a
concentration factor (CF) higher than 10 for all species. Chitosan flocculation
worked generally very well for freshwater microalgae, but not for marine species.
Alkaline flocculation was most efficient for harvesting of Nannochloropsis,
Chlamydomonas and Chlorella sp. The concentration factor was highly variable
between microalgae species. Generally, minimum flocculant dosages were highly
variable across species, which shows that flocculation may be a good harvesting
method for some species but not for others. This study shows that microalgae and
cyanobacteria species should not be selected solely based on their productivity
but also on their potential for low-cost separation.
PMID- 27611031
TI - Effect of glycerol as co-solvent on yields of bio-oil from rice straw through
hydrothermal liquefaction.
AB - This study examined the effect of glycerol used as a co-solvent on yields of bio
oil derived from rice straw through hydrothermal liquefaction (HTL). The reaction
was conducted in a high-pressure batch reactor with different volume ratios of
glycerol to water. The quality of the derived bio-oil was analyzed in terms of
its elemental composition, heating value, water content, ash content, and acid
number. Fourier transform infrared spectroscopy and gas chromatography-mass
spectrometry were conducted to analyze the chemical composition of the derived
bio-oils. The following optimal conditions were obtained: 1:1 vol ratio of
glycerol to water with 5wt% of Na2CO3 at 260 degrees C for 1h. Under these
conditions, 50.31wt% of bio-oil and 26.65wt% of solid residue were produced.
Therefore, glycerol can be used as a co-solvent in HTL of rice straw at moderate
temperatures to obtain bio-oil with high yield and quality.
PMID- 27611032
TI - Modeling and simulation of xylitol production in bioreactor by Debaryomyces
nepalensis NCYC 3413 using unstructured and artificial neural network models.
AB - This study examines the use of unstructured kinetic model and artificial neural
networks as predictive tools for xylitol production by Debaryomyces nepalensis
NCYC 3413 in bioreactor. An unstructured kinetic model was proposed in order to
assess the influence of pH (4, 5 and 6), temperature (25 degrees C, 30 degrees C
and 35 degrees C) and volumetric oxygen transfer coefficient kLa (0.14h(-1),
0.28h(-1) and 0.56h(-1)) on growth and xylitol production. A feed-forward back
propagation artificial neural network (ANN) has been developed to investigate the
effect of process condition on xylitol production. ANN configuration of 6-10-3
layers was selected and trained with 339 experimental data points from bioreactor
studies. Results showed that simulation and prediction accuracy of ANN was
apparently higher when compared to unstructured mechanistic model under varying
operational conditions. ANN was found to be an efficient data-driven tool to
predict the optimal harvest time in xylitol production.
PMID- 27611033
TI - Influence of applied voltage on the performance of bioelectrochemical anaerobic
digestion of sewage sludge and planktonic microbial communities at ambient
temperature.
AB - The influence of applied voltage on the bioelectrochemical anaerobic digestion of
sewage sludge was studied at ambient temperature (25+/-2 degrees C). The
stability of the bioelectrochemical anaerobic digestion was considerably good in
terms of pH, alkalinity and VFAs at 0.3V and 0.5V, but VFA accumulation occurred
at 0.7V. The specific methane production rate (370mLCH4/L.d) was the highest at
0.3V, but the methane content (80.6%) in biogas and the methane yield
(350mLCH4/gCODr) were higher at 0.5V, significantly better than those of 0.7V.
The VS removal efficiency was 64-66% at 0.3V and 0.5V, but only 31% at 0.7V. The
dominant species of planktonic microbial communities was Cloacamonas at 0.3V and
0.5V, but the percentage of hydrolytic bacteria species such as Saprospiraceae,
Fimbriimonas, and Ottowia pentelensis was much higher at 0.7V. The optimal
applied voltage for bioelectrochemical anaerobic digestion was 0.3-0.5V according
to digestion performance and planktonic microbial communities.
PMID- 27611036
TI - The Society of Biomolecular Imaging and Informatics 3rd Annual Conference High
Content 2016 September 12-14, 2016 Joseph B. Martin Conference Center Harvard
Medical School, Boston, MA.
PMID- 27611034
TI - Study on reactivity characteristics and synergy behaviours of rice straw and
bituminous coal co-gasification.
AB - Co-gasification of rice straw (RS) and Shenfu bituminous coal (SF) was conducted
in a thermogravimetric analyzer (TGA) to explore the effects of gasification
temperature and blend ratio on reactivity characteristics and synergy behaviours
of co-gasification. Moreover, the relationship between the synergy and the K/Ca
transformation in co-gasification was studied using flame atomic absorption
spectrum (FAAS) and in-situ heating stage microscope. The results showed that the
whole reactivities increased with increasing RS proportion and gasification
temperature. The transformation of water-soluble and ion-exchanged (ws-ie)
calcium was enhanced in whole co-gasification and the ws-ie potassium
transformation was obviously inhibited in mid-late reaction. Hence, synergy
behaviours were synthetically determined by the enhancement of Ca deactivation
and the strengthening of K catalysis. The inhibiting effect was occurred in
initial co-gasification and was converted to the synergistic effect at a
characteristic conversion, which decreased with increasing RS proportion and
decreasing gasification temperature.
PMID- 27611035
TI - Enhancing anaerobic digestion of complex organic waste with carbon-based
conductive materials.
AB - The aim of this work was to study the methanogenic metabolism of dog food, a food
waste surrogate, in laboratory-scale reactors with different carbon-based
conductive materials. Carbon cloth, carbon felt, and granular activated carbon
all permitted higher organic loading rates and promoted faster recovery of soured
reactors than the control reactors. Microbial community analysis revealed that
specific and substantial enrichments of Sporanaerobacter and Methanosarcina were
present on the carbon cloth surface. These results, and the known ability of
Sporanaerobacter species to transfer electrons to elemental sulfur, suggest that
Sporanaerobacter species can participate in direct interspecies electron transfer
with Methanosarcina species when carbon cloth is available as an electron
transfer mediator.
PMID- 27611037
TI - Paracetamol in intensive care - intravenous, oral or not at all?
PMID- 27611038
TI - Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill
patients: a randomised controlled trial.
AB - Paracetamol is a commonly used drug in the intensive care unit. There have been
reports in the literature of an association with significant hypotension, a
potentially important interaction for labile critically ill patients. Route of
administration may influence the incidence of hypotension. This single-centre,
prospective, open-label, randomised, parallel-arm, active-control trial was
designed to determine the incidence of hypotension following the administration
of paracetamol to critically ill patients. Fifty adult patients receiving
paracetamol for analgesia or pyrexia were randomly assigned to receive either the
parenteral or enteral formulation of the drug. Paracetamol concentrations were
measured at baseline and at multiple time points over 24 h. The maximal plasma
paracetamol concentration was significantly different between routes; 156 vs. 73
micromol.l(-1) [p = 0.0005] following the first dose of parenteral or enteral
paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients:
parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs.
enteral paracetamol was 2.94 (95% CI 0.97-8.92; p = 0.06). The incidence of
hypotension associated with paracetamol administration is higher than previously
reported and tends to be more frequent with parenteral paracetamol.
PMID- 27611039
TI - The effects of perineural dexmedetomidine on the pharmacodynamic profile of
femoral nerve block: a dose-finding randomised, controlled, double-blind study.
AB - This randomised, controlled, double-blind study investigated the effects of
different doses of perineural dexmedetomidine on the pharmacodynamic profile of
femoral nerve block in patients undergoing arthroscopic knee surgery. Ultrasound
guided femoral nerve block was performed before general anaesthesia using 25 ml
of bupivacaine 0.5% combined with normal saline in the control group, and 25 MUg,
50 MUg or 75 MUg of dexmedetomidine in three treatment groups (n = 15 for each
group). All patients received a standard general anaesthetic and multimodal
postoperative analgesic regimen. The use of the 50 MUg and 75 MUg dose levels of
dexmedetomidine was associated with reduction of the onset time, extension of the
duration of block, prolonged time to the first postoperative request for rescue
analgesia, and reduced postoperative morphine requirements. The times to first
request for postoperative analgesia were mean (SD) 10.8 (1.6) h in the control
group and 11.0 (7.1), 21.8 (3.0) and 28.6 (10.0) in the 25 MUg, 50 MUg and 75 MUg
treatment groups, respectively. These times were significantly longer in the 50
MUg and 75 MUg treatment groups compared with the 25 MUg (p < 0.0001) and control
group (p < 0.0001). The total 24-h postoperative morphine consumption was 7.6
(5.1) mg in the control group, and 6.5 (3.5), 3.9 (3.4), 1.8 (2.6) in the 25 MUg,
50 MUg and 75 MUg treatment groups, respectively. Postoperative morphine
consumption was significantly higher in the control group compared with the 50
MUg (p = 0.045) and the 75 MUg (p = 0.001) treatment groups. The best analgesic
profile was achieved at the 75 MUg dose, but this was associated with increased
risk of hypotension.
PMID- 27611040
TI - Odds, risks, and other numbers needed to complicate things.
PMID- 27611041
TI - Peri-operative lidocaine infusion for open radical prostatectomy.
PMID- 27611042
TI - Peri-operative lidocaine infusion for open radical prostatectomy - a reply.
PMID- 27611043
TI - Topical anaesthesia for awake fibreoptic intubation.
PMID- 27611044
TI - Postoperative sore throat - know where your airway is positioned.
PMID- 27611045
TI - Ultra-low dose spinal anaesthesia for hip fracture surgery.
PMID- 27611046
TI - Ultra-low dose intrathecal anaesthesia for hip fracture surgery - a reply.
PMID- 27611047
TI - Spinal or nerve block for knee arthroscopy?
PMID- 27611048
TI - Cox regression models for frailty in vascular surgery patients - a reply.
PMID- 27611049
TI - Intrathecal anaesthesia for day-case knee arthroscopy - a reply.
PMID- 27611050
TI - Caudal anaesthesia safety for hypospadias repair.
PMID- 27611051
TI - Caudal anesthesia safety for hypospadias repair - a reply.
PMID- 27611052
TI - Age and the anaesthetist.
PMID- 27611053
TI - Risk of exsanguination from a faulty arterial pressure transducer.
PMID- 27611054
TI - Correction.
PMID- 27611055
TI - Correction.
PMID- 27611056
TI - ASSOCIATION BETWEEN RETINAL HEMORRHAGIC PATTERNS AND PERFUSION STATUS IN EYES
WITH ACUTE CENTRAL RETINAL VEIN OCCLUSION.
AB - PURPOSE: To evaluate peripheral retinal hemorrhagic patterns in eyes with acute
central retinal vein occlusion, and to explore their clinical relevance in
differentiating for the retinal perfusion status, through a prospective, and
cross-sectional study. METHODS: Fifty eyes with acute central retinal vein
occlusion were included. Retinal hemorrhagic patterns at the equator and retinal
perfusion status were evaluated by ultra-wide field fundus photography and
fluorescein angiography. RESULTS: Retinal perfusion was categorized as
nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None
of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All
hemorrhages were rounded-dot or blot and were variable in size. Particle analysis
was performed to quantify hemorrhage size, and showed higher values in eyes
having larger blot hemorrhages, and lower values in eyes having dot or smaller
blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was
larger in eyes classified as ischemic (10,763.0 +/- 5,946.3 pixels) than as
nonischemic (2,839.9 +/- 1,153.6 pixels, P < 0.001). The authors calculated area
under the curve to investigate the ability of continuous variables to
discriminate retinal perfusion status, which was 0.963 (P < 0.001) for mean size
of maximum peripheral blot hemorrhages. CONCLUSION: The authors objectively
evaluated retinal hemorrhagic patterns at the equator in eyes with acute central
retinal vein occlusion using particle analysis. The resulting hemorrhage size
measurement was considered to be often useful in determining retinal perfusion
status. Because they can be noninvasively evaluated with readily available
equipment, peripheral hemorrhagic patterns might be good clinical markers of
retinal perfusion.
PMID- 27611057
TI - Investigation and Mathematical Description of the Real Driving Force of Passive
Transport of Drug Molecules from Supersaturated Solutions.
AB - The aim of this study was to investigate the impact of formulation excipients and
solubilizing additives on dissolution, supersaturation, and membrane transport of
an active pharmaceutical ingredient (API). When a poorly water-soluble API is
formulated to enhance its dissolution, additives, such as surfactants, polymers,
and cyclodextrins, have an effect not only on dissolution profile but also on the
measured physicochemical properties (solubility, pKa, permeability) of the drug
while the excipient is present, therefore also affecting the driving force of
membrane transport. Meloxicam, a nonsteroidal anti-inflammatory drug, was chosen
as a poorly water-soluble model drug and formulated in order to enhance its
dissolution using solvent-based electrospinning. Three polyvinylpyrrolidone (PVP)
derivatives (K30, K90, and VA 64), Soluplus, and (2-hydroxypropyl)-beta
cyclodextrin were used to create five different amorphous solid dispersions of
meloxicam. Through experimental design, the various formulation additives that
could influence the characteristics of dissolution and permeation through
artificial membrane were observed by carrying out a simultaneous dissolution
permeation study with a side-by-side diffusion cell, MUFLUX. Although the
dissolution profiles of the formulations were found to be very similar, in the
case of Soluplus containing formulation the flux was superior, showing that the
driving force of membrane transport cannot be simplified to the concentration
gradient. Supersaturation gradient, the difference in degree of supersaturation
(defined as the ratio of dissolved amount of the drug to its thermodynamic
solubility) between the donor and acceptor side, was found to be the driving
force of membrane transport. It was mathematically derived from Fick's first law,
and experimentally proved to be universal on several meloxicam containing ASDs
and DMSO stock solution.
PMID- 27611058
TI - A validated LC-MS/MS method for the quantitative measurement of creatinine as an
endogenous biomarker in human plasma.
AB - BACKGROUND: Creatinine is an endogenous compound generated from creatine by
normal muscular metabolism. It is an important indicator of renal function and
the serum level is routinely monitored in clinical labs. Results & methodology:
Surrogate analyte (d3-creatinine) was used for calibration standard and quality
control preparation and the relative instrument response ratio between creatinine
and d3-creatinine was used to calculate the endogenous creatinine concentrations.
CONCLUSION: A fit-for-purpose strategy of using a surrogate analyte and authentic
matrix was adopted for this validation. The assay was the first human plasma
assay using such strategy and was successfully applied to a clinical study to
confirm a transient elevation of creatinine observed using an existing clinical
assay.
PMID- 27611059
TI - Capacity estimates for optical transmission based on the nonlinear Fourier
transform.
AB - What is the maximum rate at which information can be transmitted error-free in
fibre-optic communication systems? For linear channels, this was established in
classic works of Nyquist and Shannon. However, despite the immense practical
importance of fibre-optic communications providing for >99% of global data
traffic, the channel capacity of optical links remains unknown due to the
complexity introduced by fibre nonlinearity. Recently, there has been a flurry of
studies examining an expected cap that nonlinearity puts on the information
carrying capacity of fibre-optic systems. Mastering the nonlinear channels
requires paradigm shift from current modulation, coding and transmission
techniques originally developed for linear communication systems. Here we
demonstrate that using the integrability of the master model and the nonlinear
Fourier transform, the lower bound on the capacity per symbol can be estimated as
10.7 bits per symbol with 500 GHz bandwidth over 2,000 km.
PMID- 27611060
TI - Promoting Children's and Adolescents' Social and Emotional Development: District
Adaptations of a Theory of Action.
AB - This article contributes to the broader discussion of promotion, prevention, and
intervention in child and adolescent mental health by describing implementation
and early outcomes of an 8-school district demonstration project aimed at making
the promotion of social and emotional learning a systemic part of school
districts' practice. Eight districts are 2-3 years in to their participation in
the 6-year project. The districts are large, are predominantly urban, and serve
many students who are at disadvantage. The evaluation involved collection of
qualitative data to measure the degree to which the districts realized the goals
established in the initiative's theory of action, as well as school climate data,
extant student records, and surveys of students' social and emotional competence.
To date, results show that districts have followed highly individual pathways
toward integrating social and emotional learning systemically, and all have made
progress over time. Although school-level implementation remains at moderate
levels, 2 districts in which we could examine school climate showed gains from
preinitiative years. Four of 6 measured districts showed improvement in social
and emotional competence for students in Grade 3, and achievement and discipline
showed overall improvements across all districts. Overall findings show that
implementation of the initiative's theory of action by school districts is
feasible, even in times of budgetary stress and leadership turnover. This
establishes the potential for school districts to serve as a lever of change in
the promotion of students' social and emotional development and mental wellness.
PMID- 27611061
TI - Time series of ground reaction forces following a single leg drop jump landing in
elite youth soccer players consist of four distinct phases.
AB - The single leg drop jump landing test may assess dynamic and static balance
abilities in different phases of the landing. However objective definitions of
different phases following landing and associated reliability are lacking.
Therefore, we determined the existence of possible distinct phases of single leg
drop jump landing on a force plate in 82 elite youth soccer players. Three
outcome measures were calculated over moving windows of five sizes: center of
pressure (COP) speed, COP sway and horizontal ground reaction force (GRF). Per
outcome measure, a Factor Analysis was employed with all windows as input
variables. It showed that four factors (patterns of variance) largely (>75%)
explained the variance across subjects/trials along the 12s time series. Each
factor was highly associated with a distinct phase of the time series signal:
dynamic (0.4-2.7s), late dynamic (2.5-5.0s), static 1 (5.0-8.3s) and static 2
(8.1-11.7s). Intra-class correlations (ICC) between trials were lower for the
dynamic phases (0.45-0.68) than for the static phases (0.60-0.86). The COP speed
showed higher ICC's (0.63-0.86) than COP sway (0.45-0.61) and GRF (0.57-0.71) for
all four phases. In conclusion, following a drop jump landing unique information
is available in four distinct phases. The COP speed is most reliable, with higher
reliability in the static phases compared to the dynamic phases. Future studies
should assess the sensitivity of information from dynamic, late dynamic and
static phases.
PMID- 27611062
TI - The threat of a support surface translation affects anticipatory postural
control.
AB - This study examined how postural threat in the form of a potential perturbation
affects an individual's ability to perform a heel raise. Seventeen adults
completed three conditions: i) low threat, where participants performed a heel
raise in response to a "go" tone, ii) high threat, where participants either
heard the same "go" tone, for which they performed a heel raise, or experienced a
support surface translation in the medio-lateral direction that disturbed their
balance, and iii) choice reaction time task, where participants either completed
a heel raise in response to the same "go" tone or a toe raise in response to a
lower pitched tone. For all heel raise trials, anticipatory postural adjustments
(APAs) were quantified from center of pressure (COP) recordings and
electromyographic (EMG) activity from the tibialis anterior (TA) and soleus
(SOL). Results indicated that participants exhibited larger APAs, as reflected by
the greater backward COP displacement (p=0.038) and velocity (p=0.022) as well as
a larger TA EMG amplitude (p=0.045), during the high threat condition. During the
execution phase of the heel raise, an earlier (p=0.014) and larger (p=0.041) SOL
EMG activation were observed during the high threat condition. These results
contrast with previous findings of reduced APAs when the postural threat was
evoked through changes in surface height. Therefore, the characteristics of the
postural threat must be considered to isolate the effects of threat on
anticipatory movement control.
PMID- 27611063
TI - Familiar faces rendered strange: Why inconsistent realism drives characters into
the uncanny valley.
AB - Computer-modeled characters resembling real people sometimes elicit cold, eerie
feelings. This effect, called the uncanny valley, has been attributed to
uncertainty about whether the character is human or living or real. Uncertainty,
however, neither explains why anthropomorphic characters lie in the uncanny
valley nor their characteristic eeriness. We propose that realism inconsistency
causes anthropomorphic characters to appear unfamiliar, despite their physical
similarity to real people, owing to perceptual narrowing. We further propose that
their unfamiliar, fake appearance elicits cold, eerie feelings, motivating threat
avoidance. In our experiment, 365 participants categorized and rated objects,
animals, and humans whose realism was manipulated along consistency-reduced and
control transitions. These data were used to quantify a Bayesian model of
categorical perception. In hypothesis testing, we found reducing realism
consistency did not make objects appear less familiar, but only animals and
humans, thereby eliciting cold, eerie feelings. Next, structural equation models
elucidated the relation among realism inconsistency (measured objectively in a
two-dimensional Morlet wavelet domain inspired by the primary visual cortex),
realism, familiarity, eeriness, and warmth. The fact that reducing realism
consistency only elicited cold, eerie feelings toward anthropomorphic characters,
and only when it lessened familiarity, indicates the role of perceptual narrowing
in the uncanny valley.
PMID- 27611064
TI - The dynamic effect of reading direction habit on spatial asymmetry of image
perception.
AB - Exploration of images after stimulus onset is initially biased to the left. Here,
we studied the causes of such an asymmetry and investigated effects of reading
habits, text primes, and priming by systematically biased eye movements on this
spatial bias in visual exploration. Bilinguals first read text primes with right
to-left (RTL) or left-to-right (LTR) reading directions and subsequently explored
natural images. In Experiment 1, native RTL speakers showed a leftward free
viewing shift after reading LTR primes but a weaker rightward bias after reading
RTL primes. This demonstrates that reading direction dynamically influences the
spatial bias. However, native LTR speakers who learned an RTL language late in
life showed a leftward bias after reading either LTR or RTL primes, which
suggests the role of habit formation in the production of the spatial bias. In
Experiment 2, LTR bilinguals showed a slightly enhanced leftward bias after
reading LTR text primes in their second language. This might contribute to the
differences of native RTL and LTR speakers observed in Experiment 1. In
Experiment 3, LTR bilinguals read normal (LTR, habitual reading) and mirrored
left-to-right (mLTR, nonhabitual reading) texts. We observed a strong leftward
bias in both cases, indicating that the bias direction is influenced by habitual
reading direction and is not secondary to the actual reading direction. This is
confirmed in Experiment 4, in which LTR participants were asked to follow RTL and
LTR moving dots in prior image presentation and showed no change in the normal
spatial bias. In conclusion, the horizontal bias is a dynamic property and is
modulated by habitual reading direction.
PMID- 27611065
TI - Meeting Abstracts - Academy of Managed Care Pharmacy Nexus 2016.
AB - The Academy of Managed Care Pharmacy (AMCP) Abstracts program provides a forum
through which authors can share their insights and outcomes of advanced managed
care practice through publication in AMCP's Journal of Managed Care & Specialty
Pharmacy (JMCP). Poster presentations are Tuesday, October 4, at 4:00 pm. The
posters will also be displayed on Wednesday, October 5. The reviewed abstracts
are published in the JMCP Meeting Abstracts supplement. The AMCP Nexus 2016
Meeting in National Harbor, Maryland, is expected to attract more than 2,000
managed care pharmacists and other health care professionals who manage and
evaluate drug therapies, develop and manage networks, and work with medical
managers and information specialists to improve the care of all individuals
enrolled in managed care programs.
PMID- 27611066
TI - Interconnections between cell wall polymers, wall mechanics, and cortical
microtubules: Teasing out causes and consequences.
AB - In plants, cell wall components including cellulose, hemicelluloses, and pectins
interact with each other to form complex extracellular network structures that
control cell growth and maintain cell shape. However, it is still not clear
exactly how different wall polymers interact, how the conformations and
interactions of cell wall polymers relate to wall mechanics, and how these
factors impinge on intracellular structures such as the cortical microtubule
cytoskeleton. Here, based on studies of Arabidopsis thaliana xxt1 xxt2 mutants,
which lack detectable xyloglucan in their walls and display aberrant wall
mechanics, altered cellulose patterning and biosynthesis, and reduced cortical
microtubule stability, we discuss the potential relationships between cell wall
biosynthesis, wall mechanics, and cytoskeletal dynamics in an effort to better
understand their roles in controlling plant growth and morphogenesis.
PMID- 27611067
TI - Impacts of dissolved organic matter on aqueous behavior of nano/micron-titanium
nitride and their induced enzymatic/non-enzymatic antioxidant activities in
Scenedesmus obliquus.
AB - Freshwater dispersion stability and ecotoxicological effects of titanium nitride
(TiN) with particle size of 20 nm, 50 nm, and 2-10 MUm in the presence of
dissolved organic matter (DOM) at various concentrations were studied. The TiN
particles that had a more negative zeta potential and smaller hydrodynamic size
showed more stable dispersion in an aqueous medium when DOM was present than when
DOM was absent. Biochemical assays indicated that relative to the control, the
TiN particles in the presence of DOM alleviated to some extent the antioxidative
stress enzyme activity in Scenedesmus obliquus. In addition, it was found that
the TiN with a primary size of 50 nm at a high concentration presented a
significant impact on non-enzymatic antioxidant defense in algal cells.
PMID- 27611068
TI - Brain derived neurotrophic factor moderates associations between maternal smoking
during pregnancy and offspring behavioral disorders.
AB - Maternal smoking during pregnancy is associated with a number of adverse
offspring outcomes. In the present study, based on 209 offspring from a 3
generation family study of depression, we show that the effects of prenatal
exposure on offspring externalizing psychopathology (conduct, substance use
disorder) is more pronounced in the presence of lower-expressing brain derived
neurotrophic factor (BDNF) gene variants. BDNF plays an important role in the
development and survival of neural circuits. Individuals with low-expressing
variants who are further exposed to prenatal tobacco smoke may be most vulnerable
to a spectrum of behavioral disorders that depend on these circuits.
PMID- 27611069
TI - Suicidal ideation among young Afghanistan/Iraq War Veterans and civilians:
Individual, social, and environmental risk factors and perception of unmet mental
healthcare needs, United States, 2013.
AB - Suicidal Ideation among Afghanistan/Iraq War Veterans remains a health concern.
As young Veterans adjust to civilian life, new risk factors might emerge and
manifest differently in this group versus those in the general population. We
explored these differences. With 2013 National Survey on Drug Use and Health
data, we examined differences in risk of past-year suicidal ideation between
Veterans of the Afghanistan/Iraq War periods aged 18-34 years (N=328) and age
comparable civilians (N=23,222). We compared groups based on individual and socio
environmental risk factors as well as perceptions of unmet mental healthcare
needs. We report adjusted rate ratios (aRRs); interaction terms tested for
between-group differences. PY suicidal ideation rates for Veterans and civilians
did not differ (52 versus 59 per 1,000, p=0.60) and both groups shared many risk
factors. However, drug problems and perceived unmet mental health care needs were
vastly stronger risk factors among Veterans versus civilians (interaction terms
indicated that the aRRs were 3.8-8.0 times higher for Veterans versus civilians).
Other differences were discovered as well. Past-year suicidal ideation rates did
not differ by Veteran status among young adults. However, different risk factors
per group were detected, which can inform Veteran suicide prevention efforts.
PMID- 27611070
TI - Expressed Emotion and behaviourally controlling interactions in the daily life of
dyads experiencing psychosis.
AB - While research using Experience Sampling Methodology (ESM) suggests that, in
general, contact with relatives or friends may be protective for psychotic
experiences, contact with high-Expressed Emotion (high-EE) relatives can have
adverse consequences for patients. This study investigated whether contact with
high-EE relatives, and relatives' behaviourally controlling interactions (BCI)
are related to patients' symptoms and to both patients' and relatives' affect
when measured using structured diary assessments in the course of everyday life.
Twenty-one patients experiencing psychosis and their closest relatives provided
synchronized self-reports of symptoms (patients only), affect, dyadic contact and
BCI over a 6-days period. Relatives' EE was obtained from Camberwell Family
Interviews. Multi-level modeling showed that patients' reports of relatives
taking control of them and helping them were associated with increased patient
negative affect and symptoms. Relatives' self-reports of nagging, taking control
and keeping an eye on the patient were related to fluctuations in relatives'
affect. No evidence was found for the moderating effect of EE status on the
association between dyadic contact and affect or, in the case of patients,
symptoms. When measured using an ecologically valid methodology, momentary
behaviourally controlling interactions within dyads experiencing psychosis can
impact on patients' affect and symptoms.
PMID- 27611071
TI - Mendelian randomization in relation to androgens and suicidal behavior in males.
PMID- 27611072
TI - Comprehensive Small RNA-Seq of Adeno-Associated Virus (AAV)-Infected Human Cells
Detects Patterns of Novel, Non-Coding AAV RNAs in the Absence of Cellular miRNA
Regulation.
AB - Most DNA viruses express small regulatory RNAs, which interfere with viral or
cellular gene expression. For adeno-associated virus (AAV), a small ssDNA virus
with a complex biphasic life cycle miRNAs or other small regulatory RNAs have not
yet been described. This is the first comprehensive Illumina-based RNA-Seq
analysis of small RNAs expressed by AAV alone or upon co-infection with helper
adenovirus or HSV. Several hotspots of AAV-specific small RNAs were detected
mostly close to or within the AAV-ITR and apparently transcribed from the newly
identified anti-p5 promoter. An additional small RNA hotspot was located
downstream of the p40 promoter, from where transcription of non-coding RNAs
associated with the inhibition of adenovirus replication were recently described.
Parallel detection of known Ad and HSV miRNAs indirectly validated the newly
identified small AAV RNA species. The predominant small RNAs were analyzed on
Northern blots and by human argonaute protein-mediated co-immunoprecipitation.
None of the small AAV RNAs showed characteristics of bona fide miRNAs, but
characteristics of alternative RNA processing indicative of differentially
regulated AAV promoter-associated small RNAs. Furthermore, the AAV-induced
regulation of cellular miRNA levels was analyzed at different time points post
infection. In contrast to other virus groups AAV infection had virtually no
effect on the expression of cellular miRNA, which underscores the long
established concept that wild-type AAV infection is apathogenic.
PMID- 27611073
TI - Compared to Intermittant Claudication Critical Limb Ischemia Is Associated with
Elevated Levels of Cytokines.
AB - Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease
(PAD) and associated with an extremely poor clinical outcome. In order to
understand the possible role of circulating cytokines and poor outcome associated
with CLI we compared the circulating cytokine profile of patients with CLI
against patients with intermittent claudication (IC). The levels of 48
circulating cytokines were examined in 226 consecutive patients with peripheral
artery disease (PAD) admitted for elective, non-urgent, invasive treatment of IC
or CLI. The PAD patient cohort was evenly distributed between subjects with IC
(46.5%) and CLI (53.5%). As accustomed in PAD, CLI was associated with higher
age, chronic kidney disease and diabetes when compared to IC (P < 0.01 for all).
In multivariable linear regression modeling taking into account the baseline
differences between IC and CLI groups CLI was independently associated with
elevated levels of a large number of cytokines: IL-1beta, IL-1ra, IL-2Ralpha, IL
4, IL-6, IL-10, IFN-gamma, GM-CSF, G-CSF (P < 0.01 for all), and IL-2, IL-7, IL
12, IL-13, IL-17, bFGF, VEGF, SCGF-beta (P < 0.05 for all). The current findings
indicate that CLI is associated with a circulating cytokine profile, which
resembles serious medical conditions such as severe pancreatitis, sepsis, or even
cancer. Compared to IC, CLI is a systemic inflammatory condition, which may
explain the extremely poor outcome associated with it.
PMID- 27611074
TI - Impact of sensory design interventions on image quality, patient anxiety and
overall patient experience at MRI.
AB - OBJECTIVE: This study aimed to assess the effect of sensory stimulation on
patient MRI experience and to assess whether sensory stimulation has a
significant effect on MR image quality. METHODS: A case-control study was
conducted over 4 months, involving patients undergoing MRI brain, cervical spine,
breast and prostate. The study involved 106 patients, 64 cases and 42 controls.
Cases underwent sensory stimulation during the scan in the form of a scented
cotton pad placed in the scanner near their head and/or calming bird noises were
played over headphones. Post-scan, participants completed a questionnaire
regarding their experience of MRI. Scanning radiographers completed a
questionnaire regarding patient tolerance of the scan. All studies were evaluated
by two radiologists for the presence of movement artefact. RESULTS: 39% of cases
and 38% of controls reported anxiety in the days preceding MRI. 6.2% of cases
required coaching during image acquisition, while 9.7% of controls required
coaching. 4.7% of cases and 4.8% controls required sequence repetition owing to
movement artefact. Mean patient experience score (as graded by the patient) for
controls was 1.74 +/- 0.63 standard deviation (SD) and for cases, it was 1.67 +/-
0.60 SD. (Lower assigned scores equated to a better experience). Mean patient
experience score based on comments on a 5-point scale as graded by two observers
was 2.81 +/- 0.70 SD for controls, 2.42 + 0.94 SD for sound intervention and 2.46
+/- 1.01 SD for scent intervention. Mean motion artefact score graded by the two
radiologists was 1.13 +/- 0.53 SD for controls and 1.08 +/- 0.36 SD for cases. (A
lower score equated to less movement artefact). We demonstrated a trend towards a
relaxing experience in those patients undergoing MRI for the first time who
underwent sensory intervention. Participant positive ratings of the smell
pleasantness were associated with a reduced likelihood of experiencing anxiety (p
= 0.13). Results were not statistically significant. CONCLUSION: This study
demonstrated a subjectively improved experience of MRI for some patients with the
intervention of sound and smell. The study failed to show a significant decrease
in patient movement during MRI investigations. This may relate to the small study
size and a low level of patient movement in the case group. Advances in
knowledge: Sound and olfactory sensory environment interventions at MRI can
improve the patient experience. These low-cost interventions are well tolerated,
may improve acceptance of MRI in patients with anxiety and offer a competitive
advantage to imaging centres.
PMID- 27611076
TI - Correction: Validation of the Surgical Fear Questionnaire in Adult Patients
Waiting for Elective Surgery.
AB - [This corrects the article DOI: 10.1371/journal.pone.0100225.].
PMID- 27611075
TI - Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to
Interfering with Mesangial Cell Collagen Production in a Hyperglycaemic Setting.
AB - Extracellular vesicles (EVs) that are derived from stem cells are proving to be
promising therapeutic options. We herein investigate the therapeutic potential of
EVs that have been derived from different stem cell sources, bone-marrow (MSC)
and human liver (HLSC), on mesangial cells (MCs) exposed to hyperglycaemia. By
expressing a dominant negative STAT5 construct (DeltaNSTAT5) in HG-cultured MCs,
we have demonstrated that miR-21 expression is under the control of STAT5, which
translates into Transforming Growth Factor beta (TGFbeta) expression and collagen
production. A number of approaches have been used to show that both MSC- and HLSC
derived EVs protect MCs from HG-induced damage via the transfer of miR-222. This
resulted in STAT5 down-regulation and a decrease in miR-21 content, TGFbeta
expression and matrix protein synthesis within MCs. Moreover, we demonstrate that
changes in the balance between miR-21 and miR-100 in the recipient cell, which
are caused by the transfer of EV cargo, further contribute to providing
beneficial effects. Interestingly, these effects were only detected in HG
cultured cells. Finally, it was found that HG reduced the expression of the
nuclear encoded mitochondrial electron transport chain (ETC) components, CoxIV.
It is worth noting that EV administration can rescue CoxIV expression in HG
cultured MCs. These results thus demonstrate that both MSC- and HLSC-derived EVs
transfer the machinery needed to preserve MCs from HG-mediated damage. This
occurs via the horizontal transfer of functional miR-222 which directly
interferes with damaging cues. Moreover, our data indicate that the release of EV
cargo into recipient cells provides additional therapeutic advantages against
harmful mitochondrial signals.
PMID- 27611077
TI - Experimental Treatment of Ebola Virus Disease with Brincidofovir.
AB - BACKGROUND: The nucleotide analogue brincidofovir was developed to prevent and
treat infections caused by double-stranded DNA viruses. Based on in vitro data
suggesting an antiviral effect against Ebola virus, brincidofovir was included in
the World Health Organisation list of agents that should be prioritised for
clinical evaluation in patients with Ebola virus disease (EVD) during the West
African epidemic. METHODS AND FINDINGS: In this single-arm phase 2 trial
conducted in Liberia, patients with laboratory-confirmed EVD (two months of age
or older, enrolment bodyweight >=50 kg) received oral brincidofovir 200 mg as a
loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14.
Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment.
The primary outcome was survival at Day 14 after the first dose of brincidofovir.
Four patients were enrolled between 01 January 2015 and 31 January 2015. The
trial was stopped following the decision by the manufacturer to terminate their
program of development of brincidofovir for EVD. No Serious Adverse Reactions or
Suspected Unexpected Serious Adverse Reactions were identified. All enrolled
subjects died of an illness consistent with EVD. CONCLUSIONS: Due to the small
sample size it was not possible to determine the efficacy of brincidofovir for
the treatment of EVD. The premature termination of the trial highlights the need
to establish better practices for preclinical in-vitro and animal screening of
therapeutics for potentially emerging epidemic infectious diseases prior to their
use in patients. TRIAL REGISTRATION: Pan African Clinical Trials Registry
PACTR201411000939962.
PMID- 27611079
TI - Fission product decontamination factors for plutonium separated by PUREX from low
burnup, fast-neutron irradiated depleted UO2.
AB - Experimental investigations to determine fission product separation from
actinides (U and Pu) while employing the Plutonium Uranium Recovery by Extraction
(PUREX) process to purify plutonium produced in a fast neutron irradiated
depleted uranium dioxide (DUO2) target were conducted. The sample was a DUO2
pellet (0.256wt% 235U) irradiated to a low-burnup (4.43+/-0.31GWd/tHM) that was
PUREX processed 538 days after neutron irradiation. Decontamination factors (DF)
for the elements U, Mo, Ru, Ce, Sm, Sr, Pm, Eu, Nd, Pd, and Cd were measured with
mass spectroscopy in two experiments using 30vol% tri-n-butyl phosphate (TBP) in
a kerosene diluent. The first experiment characterized Pu DFs for a single stage
extraction and back-extraction, while the second experiment had multiple stages
with the goal of achieving greater Pu recovery. The benchtop scale PUREX process
had overall Pu recoveries of (83.4+/-9.5)% and (99.7+/-4.2)% for the first and
second experiments, respectively.
PMID- 27611078
TI - The Recently Identified Isoleucine Conjugate of cis-12-Oxo-Phytodienoic Acid Is
Partially Active in cis-12-Oxo-Phytodienoic Acid-Specific Gene Expression of
Arabidopsis thaliana.
AB - Oxylipins of the jasmonate family are active as signals in plant responses to
biotic and abiotic stresses as well as in development. Jasmonic acid (JA), its
precursor cis-12-oxo-phytodienoic acid (OPDA) and the isoleucine conjugate of JA
(JA-Ile) are the most prominent members. OPDA and JA-Ile have individual
signalling properties in several processes and differ in their pattern of gene
expression. JA-Ile, but not OPDA, is perceived by the SCFCOI1-JAZ co-receptor
complex. There are, however, numerous processes and genes specifically induced by
OPDA. The recently identified OPDA-Ile suggests that OPDA specific responses
might be mediated upon formation of OPDA-Ile. Here, we tested OPDA-Ile-induced
gene expression in wild type and JA-deficient, JA-insensitive and JA-Ile
deficient mutant background. Tests on putative conversion of OPDA-Ile during
treatments revealed only negligible conversion. Expression of two OPDA-inducible
genes, GRX480 and ZAT10, by OPDA-Ile could be detected in a JA-independent manner
in Arabidopsis seedlings but less in flowering plants. The data suggest a
bioactivity in planta of OPDA-Ile.
PMID- 27611080
TI - Selective removal of uranium ions from contaminated waters using modified-X
nanozeolite.
AB - In order to efficiently remove of uranium anionic species (which are the most
dominant species of uranium in natural water at neutral pH) from contaminated
waters, nano-NaX zeolite was synthesized and then modified using various divalent
cations (Mg2+, Ca2+, Mn2+) and ZnO nanoparticles (from 1.7 to 10.3wt%). Different
characterization techniques of XRF, XRD, FE-SEM, TEM, FT-IR, and AAS were used to
characterize the final synthesized absorbents. Sorption experiments by batch
technique were done to study the effect of solid-liquid ratio, initial uranium
concentration, contact time and temperature under neutral condition of pH and
presence of all anions and cations which are available in the waters. Results
showed that although nano-NaX zeolite due to its negative framework charge had a
low sorption capacity for adsorption of uranium anionic species, but modification
of parent nano-NaX zeolite with ZnO nanoparticles and various cations effectively
improved its uranium adsorption capacity. Also, results showed that under optimum
condition of pH=7.56, contact time of 60min at 27 degrees C with solid-liquid
ratio of 20g/L a maximum uranium removal efficiency of 99.7% can be obtained in
the presence of all anions and cations which are available in the drinking waters
by NaX/ZnO nanocomposite.
PMID- 27611081
TI - An effective dose assessment technique with NORM added consumer products using
skin-point source on computational human phantom.
AB - The aim of this study is to develop the assessment technique of the effective
dose by calculating the organ equivalent dose with a Monte Carlo (MC) simulation
and a computational human phantom for the naturally occurring radioactive
material (NORM) added consumer products. In this study, we suggests the method
determining the MC source term based on the skin-point source enabling the
convenient and conservative modeling of the various type of the products. To
validate the skin-point source method, the organ equivalent doses were compared
with that by the product modeling source of the realistic shape for the pillow,
waist supporter, sleeping mattress etc. Our results show that according to the
source location, the organ equivalent doses were observed as the similar tendency
for both source determining methods, however, it was observed that the annual
effective dose with the skin-point source was conservative than that with the
modeling source with the maximum 3.3 times higher dose. With the assumption of
the gamma energy of 1MeV and product activity of 1Bqg-1, the annual effective
doses of the pillow, waist supporter and sleeping mattress with skin-point source
was 3.09E-16SvBq-1year-1, 1.45E-15SvBq-1year-1, and 2,82E-16SvBq-1year-1,
respectively, while the product modeling source showed 9.22E-17SvBq-1year-1,
9.29E-16SvBq-1year-1, and 8.83E-17SvBq-1year-1, respectively. In conclusion, it
was demonstrated in this study that the skin-point source method could be
employed to efficiently evaluate the annual effective dose due to the usage of
the NORM added consumer products.
PMID- 27611082
TI - A mild, rapid synthesis of freebase [11C]nicotine from [11C]methyl triflate.
AB - A rapid, mild radiosynthesis of freebase [11C]nicotine was developed by the
methylation of freebase nornicotine with [11C]methyl triflate in acetone (5min,
45 degrees C). A basic (pH 10.5-11.0) HPLC system reproducibly yielded freebase
[11C]nicotine as a well-defined single peak. The freebase [11C]nicotine was
concentrated by solid phase extraction and formulated in 50uL ethanol
(370MBq/50uL) without evaporative loss suitable for a cigarette spiking study. A
radiochemical yield of 60.4+/-4.7% (n=3), radiochemical purity >=99.9% and
specific activity of 648GBq/umol at EOB for 5min beams were achieved.
PMID- 27611083
TI - Systematic Review and Meta-Analysis of Surgical Zipper Technique versus
Intracutaneous Sutures for the Closing of Surgical Incision.
AB - BACKGROUND: It is controversial whether surgical zipper technique (SZT), a non
invasive method of surgical wound closure, achieves a better outcome of incision
healing than intracutaneous sutures (IS) in the surgery. This meta-analysis was
performed to systematically analyze whether surgical zipper is superior to suture
material for the incision closure. METHODS: Databases and reference lists were
searched for randomized controlled trials (RCTs) comparing SZT with IS for the
incision closure. RESULTS: Four RCTs with 678 patients were identified and
analyzed. Compared with IS, SZT achieved similar incidence of postoperative
complications, less time for incision closure, less cost of both surgeons' time
and operating room time, no need for removing sutures and more comfort for the
patients. Besides, SZT achieved perfect aesthetic results in various types of
incisions with the exception of those with substantial curvatures, those with
secretions, in obese patients or those under high tension. CONCLUSION: The non
invasive zipper technique may be a more attractive option of incision closure in
a wide spectrum of surgical areas.
PMID- 27611084
TI - Correction: Trunk Stability, Trunk Strength and Sport Performance Level in Judo.
AB - [This corrects the article DOI: 10.1371/journal.pone.0156267.].
PMID- 27611085
TI - Novel protective mechanism of reducing renal cell damage in diabetes: Activation
AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage.
AB - Exposure of renal cells to high glucose (HG) during diabetes has been recently
proposed to be involved in renal injury. In the present study, we investigated a
potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8
oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG
and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in
OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition,
activation of AMPK by AICAR resulted in an increase raptor phosphorylation at
Ser792 and leads to increase the promoter activity of OGG1 through upregulation
of Nrf2. Downregulation of AMPK by DN-AMPK and raptor and Nrf2 by siRNA resulted
in significant decease in promoter activity and protein expression of OGG1. On
the other hand, downregulation of Akt by DN-Akt and rictor by siRNA resulted in
significant increase in promoter activity and protein expression of Nrf2 and
OGG1. Moreover, gel shift analysis shows reduction of Nrf2 binding to OGG1
promoter in cells treated with HG while cells treated with AICAR reversed the
effect of HG. Furthermore, db/db mice treated with AICAR show significant
increased in AMPK and raptor phosphroylation as well as OGG1 and Nrf2 protein
expression that associated with significant decrease in oxidative DNA damage (8
oxodG) compared to non-treated mice. In summary, our data provide a novel
protective mechanism by which AICAR prevents renal cell damage in diabetes and
the consequence complications of hyperglycemia with a specific focus on
nephropathy.
PMID- 27611086
TI - Nuclear Expression of GS28 Protein: A Novel Biomarker that Predicts Worse
Prognosis in Cervical Cancers.
AB - OBJECTIVE: The protein GS28 (28-kDa Golgi SNARE protein) has been described as a
SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors)
protein family member that plays a critical role in mammalian ER-Golgi or intra
Golgi vesicle transport. Little is known about the possible roles of GS28 in
pathological conditions. The purpose of this study was to evaluate GS28
expression in cervical cancer tissues and explore its correlation with
clinicopathological features and prognosis. METHODS: We investigated GS28
expression in 177 cervical cancer tissues by using immunohistochemistry and
evaluated the correlation of GS28 expression with clinicopathological features,
the expression of p53 and Bcl-2, and prognosis of cervical cancer patients.
Immunoblotting was performed using six freshly frozen cervical cancer tissues to
confirm the subcellular localization of GS28. RESULTS: Immunoreactivity of GS28
was observed in both nuclear and cytoplasmic compartments of cervical cancer
cells. High nuclear expression of GS28 was associated with advanced tumor stages
(P = 0.036) and negative expression of p53 (P = 0.036). In multivariate analyses,
patients with high nuclear expression of GS28 showed significantly worse overall
survival (OS) (hazard ratio = 3.785, P = 0.003) and progression-free survival
(PFS) (hazard ratio = 3.019, P = 0.008), compared to those with low or no nuclear
expression. It was also a reliable, independent prognostic marker in subgroups of
patients with early stage T1 and negative lymph node metastasis in OS (P = 0.008
and 0.019, respectively). The nuclear expression of GS28 was confirmed by
immunoblotting. CONCLUSION: High nuclear expression of GS28 is associated with
poor prognosis in early-stage cervical cancer patients. GS28 might be a novel
prognostic marker and a potential therapeutic target in cervical cancer
treatment.
PMID- 27611087
TI - Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells
From Huntington's Disease Patients.
AB - Metabolic dysfunction is well-documented in Huntington's disease (HD). However,
the link between the mutant huntingtin (mHTT) gene and the pathology is unknown.
The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the
production of NADH for conversion to ATP via the electron transport chain (ETC).
The objective of this study was to test for differences in enzyme activities,
mRNAs and protein levels related to the TCA cycle between lymphoblasts from
healthy subjects and from patients with HD. The experiments utilize the
advantages of lymphoblasts to reveal new insights about HD. The large quantity of
homogeneous cell populations permits multiple dynamic measures to be made on
exactly comparable tissues. The activities of nine enzymes related to the TCA
cycle and the expression of twenty-nine mRNAs encoding for these enzymes and
enzyme complexes were measured. Cells were studied under baseline conditions and
during metabolic stress. The results support our recent findings that the
activities of the pyruvate dehydrogenase complex (PDHC) and succinate
dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected
depression in MDH activities. Furthermore, message levels for isocitrate
dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were
responsive to treatments. The use of lymphoblasts allowed us to clarify that the
reported decrease in aconitase activity in HD autopsy brains is likely due to
secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the
TCA cycle are critical therapeutic targets that have been understudied in HD.
PMID- 27611088
TI - Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV
Vaccine. A Registry Based Case-Control Study.
AB - BACKGROUND: Since 2013 the number of suspected adverse reactions to the
quadrivalent human papillomavirus (HPV) vaccine reported to the Danish Medicines
Agency (DMA) has increased. Due to the resulting public concerns about vaccine
safety, the coverage of HPV vaccinations in the childhood vaccination programme
has declined. The aim of the present study was to determine health care-seeking
prior to the first HPV vaccination among females who suspected adverse reactions
to HPV vaccine. METHODS: In this registry-based case-control study, we included
as cases vaccinated females with reports to the DMA of suspected severe adverse
reactions. We selected controls without reports of adverse reactions from the
Danish vaccination registry and matched by year of vaccination, age of
vaccination, and municipality, and obtained from the Danish National Patient
Registry and The National Health Insurance Service Register the history of health
care usage two years prior to the first vaccine. We analysed the data by logistic
regression while adjusting for the matching variables. RESULTS: The study
included 316 cases who received first HPV vaccine between 2006 and 2014. Age
range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the
recommended age at vaccination, and another peak at 19 to 28 years, corresponding
to a catch-up programme targeting young women. Compared with 163,910 controls,
cases had increased care-seeking in the two years before receiving the first HPV
vaccine. A multivariable model showed higher use of telephone/email consultations
(OR 1.9; 95% CI 1.2-3.2), physiotherapy (OR 2.1; 95% CI 1.6-2.8) and
psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7). Cases were more likely to
have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR
1.6; 95% CI 1.0-2.4), of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2),
symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5) as well as
injuries (OR 1.5; 95% CI 1.2-1.9). CONCLUSION: Before receiving the first HPV
vaccination, females who suspected adverse reactions has symptoms and a health
care-seeking pattern that is different from the matched population. Pre
vaccination morbidity should be taken into account in the evaluation of vaccine
safety signals.
PMID- 27611089
TI - The Neurite Outgrowth Inhibitory Nogo-A-Delta20 Region Is an Intrinsically
Disordered Segment Harbouring Three Stretches with Helical Propensity.
AB - Functional recovery from central neurotrauma, such as spinal cord injury, is
limited by myelin-associated inhibitory proteins. The most prominent example,
Nogo-A, imposes an inhibitory cue for nerve fibre growth via two independent
domains: Nogo-A-Delta20 (residues 544-725 of the rat Nogo-A sequence) and Nogo-66
(residues 1026-1091). Inhibitory signalling from these domains causes a collapse
of the neuronal growth cone via individual receptor complexes, centred around
sphingosine 1-phosphate receptor 2 (S1PR2) for Nogo-A-Delta20 and Nogo receptor 1
(NgR1) for Nogo-66. Whereas the helical conformation of Nogo-66 has been studied
extensively, only little structural information is available for the Nogo-A
Delta20 region. We used nuclear magnetic resonance (NMR) spectroscopy to assess
potential residual structural propensities of the intrinsically disordered Nogo-A
Delta20. Using triple resonance experiments, we were able to assign 94% of the
non-proline backbone residues. While secondary structure analysis and relaxation
measurements highlighted the intrinsically disordered character of Nogo-A
Delta20, three stretches comprising residues 561EAIQESL567, 639EAMNVALKALGT650,
and 693SNYSEIAK700 form transient alpha-helical structures. Interestingly,
561EAIQESL567 is situated directly adjacent to one of the most conserved regions
of Nogo-A-Delta20 that contains a binding motif for beta1-integrin. Likewise,
639EAMNVALKALGT650 partially overlaps with the epitope recognized by 11C7, a Nogo
A-neutralizing antibody that promotes functional recovery from spinal cord
injury. Diffusion measurements by pulse-field gradient NMR spectroscopy suggest
concentration- and oxidation state-dependent dimerisation of Nogo-A-Delta20.
Surprisingly, NMR and isothermal titration calorimetry (ITC) data could not
validate previously shown binding of extracellular loops of S1PR2 to Nogo-A
Delta20.
PMID- 27611090
TI - Evidence for Acute Myocardial and Skeletal Muscle Injury after Serial
Transthoracic Shocks in Healthy Swine.
AB - BACKGROUND: Previous serological studies have shown controversial results whether
defibrillation or cardioversion can cause myocardial injury. Cardiovascular
Magnetic Resonance (CMR) can be used to detect myocardial edema, hyperemia and
capillary leak as features of acute myocardial injury. The aim of this study was
to assess for myocardial and skeletal muscle injury in swine following
transthoracic shocks. METHODS: Seventeen anaesthetized swine were examined, with
11 undergoing five synchronized transthoracic shocks (200J). Myocardial and
skeletal muscle injury were assessed at baseline and up to 5h post-shock
employing T1 mapping, T2 mapping, early and late gadolinium enhancement.
Serologic markers (cFABP, TnI, CK, and CK-MB) and myocardial tissue were assessed
by standard histology methods. RESULTS: In myocardial regions within the shock
path, T1 and T2 were significantly increased compared to remote myocardium in the
same animals. The early gadolinium enhancement ratio between the left-ventricular
myocardium and the right pectoral muscle was also increased compared to control
animals. After the shocks cFABP and CK were significantly elevated. After shock
application, the regions identified as abnormal by CMR showed significantly
increased interstitial and myocardial cell areas in histological analysis. This
increased cell area suggests significant cellular and interstitial edema.
CONCLUSION: Our pilot study data indicate that serial defibrillator shocks lead
to acute skeletal muscle and myocardial injury. CMR is a useful tool to detect
and localize myocardial and skeletal muscle injury early after transthoracic
shocks in vivo. In the future the technique could potentially be used as an
additional tool for quality control such as verifying insufficient local shock
application in non-responders after cardioversion or to develop safer shock
forms.
PMID- 27611092
TI - Exploring the effect of sound and music on health in hospital settings: A
narrative review.
AB - BACKGROUND: Sound in hospital space has traditionally been considered in negative
terms as both intrusive and unwanted, and based mainly on sound levels. However,
sound level is only one aspect of the soundscape. There is strong evidence that
exploring the positive aspect of sound in a hospital context can evoke positive
feelings in both patients and nurses. Music psychology studies have also shown
that music intervention in health care can have a positive effect on patient's
emotions and recuperating processes. In this way, hospital spaces have the
potential to reduce anxiety and stress, and make patients feel comfortable and
secure. This paper describes a review of the literature exploring sound
perception and its effect on health care. DATA SOURCES AND REVIEW METHODS: This
review sorted the literature and main issues into themes concerning sound in
health care spaces; sound, stress and health; positive soundscape; psychological
perspective of music and emotion; music as a complementary medicine for improving
health care; contradicting arguments concerning the use of music in health care;
and implications for clinical practice. Using Web of Science, PubMed, Scopus,
ProQuest Central, MEDLINE, and Google, a literature search on sound levels, sound
sources and the impression of a soundscape was conducted. The review focused on
the role and use of music on health care in clinical environments. In addition,
other pertinent related materials in shaping the understanding of the field were
retrieved, scanned and added into this review. RESULTS: The result indicated that
not all noises give a negative impression within healthcare soundscapes.
Listening to soothing music was shown to reduce stress, blood pressure and post
operative trauma when compared to silence. Much of the sound conveys meaningful
information that is positive for both patients and nurses, in terms of soft wind,
bird twitter, and ocean sounds. CONCLUSIONS: Music perception was demonstrated to
bring about positive change in patient-reported outcomes such as eliciting
positive emotion, and decreasing the levels of stressful conditions. Whilst sound
holds both negative and positive aspects of the hospital ecosystem and may be
stressful, it also possesses a soothing quality that induces positive feelings in
patients. Conceptualizing the nature of sound in the hospital context as a
soundscape, rather than merely noise can permit a subtler and socially useful
understanding of the role of sound and music in the hospital setting, thereby
creating a means for improving the hospital experience for patients and nurses.
PMID- 27611091
TI - Underweight Is an Independent Risk Factor for Renal Function Deterioration in
Patients with IgA Nephropathy.
AB - Studies on the relationship between body mass index (BMI) and renal progression
in IgA Nephropathy (IgAN) were limited, especially for underweight patients with
IgAN. To elucidate the clinical features and effect of underweight on renal
function deterioration in this disease, we recruited IgAN patients with
diagnostic age >=18 years old and a baseline estimated glomerular filtration rate
(eGFR) >=15 ml/min/1.73m2 from our center between 1985 and 2014. Patients
secondary to systemic diseases or follow-up less than 6 months were excluded. All
patients' clinical data at renal biopsy and during follow-up were recorded. Renal
outcome was defined as end-stage kidney disease (ESRD). Baseline body mass index
(BMI) was calculated by weight (kg) over squared height (m2). According to WHO
Asian guideline, BMI was categorized as follows: <18.5kg/m2 (underweight), 18.5
22.99kg/m2 (normal weight), 23-27.49kg/m2 (overweight) and obese (>=27.5 kg/m2).
Of 930 primary IgAN patients enrolled in this study, mean age at renal biopsy was
37.6 years and 49.2% were men. Totally, 114 (12.3%) ESRD occurred after a mean
follow-up of 47.1 months. More ESRD happened in underweight patients (17.3%)
compared to patients with normal weight (13.2%), overweight (11.0%) or obesity
(9.5%). By multivariate Cox regression analysis, underweight was independently
associated with a higher risk of ESRD after adjustment for demographic
characteristics and clinical variables (HR: 3.5, 95% CI: 1.3-9.5, P = 0.01)
comparing to normal weight. Underweight patients had lower hemoglobin, serum uric
acid, triglycerides, cholesterol and lymphocyte counts than patients with normal
weight. Furthermore, BMI was positively correlated with serum C3 (r = 0.25, p
<0.001). Our research finds that underweight is an independent risk factor for
kidney disease progression in IgAN, which might be associated with malnutrition
status and decreased C3 levels.
PMID- 27611093
TI - Collaborative nurse-led self-management support for primary care patients with
anxiety, depressive or somatic symptoms: Cluster-randomised controlled trial
(findings of the SMADS study).
AB - BACKGROUND: Collaborative, nurse-led care is a well-established model of
ambulatory care in many healthcare systems. Nurses play a key role in managing
patients' conditions as well as in enhancing symptom- and self-management skills.
OBJECTIVE: The SMADS trial evaluated the effectiveness of a primary care-based,
nurse-led, complex intervention to promote self-management in patients with
anxiety, depressive or somatic symptoms. Change in self-efficacy 12 months post
baseline was used as the primary outcome. DESIGN: The SMADS trial set up a two
arm, cluster randomised controlled trial in the city of Hamburg, a large
metropolitan area in the North West of Germany. SETTING: We randomly allocated
participating primary care practices to either the intervention group (IG),
implementing a nurse-led collaborative care model, or to the control group (CG),
where patients with the above psychosomatic symptoms received routine treatment.
PARTICIPANTS: Patients from 18 to 65 years of age, regularly consulting a
participating primary care practice, scoring>=5 on the anxiety, depressive or
somatic symptom scales of the Patient Health Questionnaire (PHQ-D), German
version. METHODS: A mixed model regression approach was used to analyse the
outcome data. Analyses were based on the intention-to-treat population: All
enrolled patients were analysed at their follow-up. Additionally, we reported
results as effect sizes. The robustness of the results was investigated by
performing an observed cases analysis. RESULTS: 325 participants (IG N=134, CG
N=191) from ten practices in each study arm consented to take part and completed
a baseline assessment. The mean group difference (ITT-LOCF, IG vs. CG) in self
efficacy at the post baseline follow-up (median 406days) was 1.65 points (95% CI
0.50-2.8) in favour of IG (p=0.004). This amounts to a small Cohen's d effect
size of 0.33. An observed cases analysis (168 participants, IG=56, CG=105)
resulted in a mean difference of 3.13 (95% CI 1.07-5.18, p=0.003) between the
groups, amounting to a moderate effect size of d=0.51. CONCLUSION: A complex,
nurse-led intervention, implemented as a collaborative care model, increased
perceived self-efficacy in patients with symptoms of anxiety, depression or
somatisation compare to control patients. For the first time in the German
healthcare system, the SMADS trial validated the belief that a nurse can
successfully complement the work of a general practitioner - particularly in
supporting self-management of patients with psychosomatic symptoms and their
psychosocial needs.
PMID- 27611095
TI - Biomaterial strategies to improve the efficacy of bone marrow cell therapy for
myocardial infarction.
AB - INTRODUCTION: The feasibility and safety of bone marrow cell (BMC) therapy for
cardiac repair following myocardial infarction has been demonstrated in clinical
studies, albeit with relatively modest structural and functional benefits. In
response to the shortcomings of BMC therapy, the use of biomaterials to enhance
cell transplantation is being investigated. Areas covered: The authors first
review what has been learned from BMC therapies for the treatment of myocardial
infarction in animal models and in clinical trials. Some issues that may be
limiting the efficacy of BMC therapy are then described. Lastly, they summarize
several biomaterial approaches that have been reported to improve transplanted
cell retention and functional outcome, and then focus on how a material can
enhance cell function such as proliferation, viability, endothelial
differentiation and angiogenic potential. Expert opinion: Improvements are needed
if BMC therapy is to become a viable treatment in the clinic. There is optimism
that a biomaterial strategy will lead to superior results compared to the cell
therapy alone. Through the identification of underlying cell-biomaterial
mechanisms, the establishment of comparative standards, and an awareness of the
lessons learned from cell therapy trials, biomaterial-enhanced BMC therapy may
become an option for the treatment of heart disease patients.
PMID- 27611094
TI - Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary
Tumorigenesis in Ovariectomized Rats without Progesterone.
AB - A role for estrogens in breast cancer is widely accepted, however, recent
evidence highlights that timing and exposure levels are important in determining
whether they elicit harmful versus beneficial effects. The rat chemical
carcinogen model has been widely used to study the effects of estrogens but
conclusions on the levels that lead to tumor development and an absolute
requirement for progesterone (P4) are lacking. A newer method of hormone
administration mixes hormones with nut butter for peroral consumption allowing
for a less stressful method of long-term administration with lower spikes in
serum estradiol (E2) levels. The present study was designed to determine if
estrogens alone at a physiological dose can drive carcinogen-induced tumors in
ovariectomized (OVX) rats or if P4 is also required using this method of hormone
administration. Short-term studies were conducted to determine the dose of
estrogen (E) that would lead to increased uterine weight following OVX.
Subsequently, rats were OVX on postnatal day (PND) 40 then treated daily with E
(600 MUg/kg/day), P4 (15 mg/kg/day), or the combination. On PND 50, all rats were
injected with nitrosomethylurea to induce mammary tumors. Uterine weights, body
weights, and serum E2 levels were measured to demonstrate the efficacy of the
method for increasing E2 levels during long-term treatment. After 26 weeks, tumor
incidence was similar in Sham, E, and E + P4 animals indicating that E was
sufficient to induce tumorigenesis when hormone levels were normalized by this
method. This study demonstrates peroral administration can be used in long-term
studies to elucidate relationships between different types and levels of steroid
hormones.
PMID- 27611096
TI - Pharmacokinetics and tissue distribution study of prucalopride in rats by ultra
high performance liquid chromatography with tandem mass spectrometry.
AB - A sensitive, reliable and high throughput ultra high performance liquid
chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed
and validated for the determination of prucalopride in rat plasma and various
tissues (including heart, liver, spleen, lung, kidney, stomach,small intestine,
large intestine, cecum, cerebrum, cerebellum, and ovary). The plasma and tissues
samples were treated by protein precipitation with acetonitrile using
carbamazepine as an internal standard (IS). Chromatographic separation was
performed on a Waters ACQUITY UPLC(r) HSS C18 column (2.1mm*50mm, 1.8MUm) with a
gradient mobile phase consisting of acetonitrile-water (containing 0.1% formic
acid) as mobile phase at a flow rate of 0.2mL/min. The quantification was
performed by multiple reactions monitoring mode with m/z 367.99->195.89 for
prucalopride and m/z 236.97->194.04 for carbamazepine on a Waters Xevo TQD mass
spectrometry equipped with electrospray ionization (ESI) source. The calibration
curve was linear in the range of 0.1-100ng/mL for plasma and various tissues
(r>=0.99) with a lower limit of quantification of 0.1ng/mL. The recoveries
obtained for prucalopride were more than 85%. The validated method was
successfully applied to the pharmacokinetics and tissue distribution study of
prucalopride after oral administration to rats. The pharmacokinetic parameters
were demonstrated as followed: the time to reach peak concentration (Tmax) was
1.0h, and the peak concentration (Cmax) was 21.71+/-4.28ng/mL, the half-life
(t1/2) was 18.21+/-0.69h, and the area under the curve (AUC) was 59.30+/
9.43ngh/mL. Tissue distribution showed the highest level was observed in stomach
and intestine, then in liver, which indicated that prucalopride was absorbed
firstly in stomach and intestine, and mainly accumulated in liver. It was also
the first study to investigate the tissue distribution of prucalopride in rats
following oral administration.
PMID- 27611097
TI - Nanoscopic tumor tissue distribution of platinum after intraperitoneal
administration in a xenograft model of ovarian cancer.
AB - There is increasing interest in the treatment of advanced stage ovarian cancer
(OC) using intraperitoneal (IP) delivery of platinum (Pt)-based chemotherapy. The
antitumor efficacy of IP chemotherapy is determined by efficient tumor tissue
penetration. Although it is assumed that Pt penetration is limited to a few
millimeters after IP delivery, little is known on the distribution of Pt in
different tumor compartments at the ultrastructural level following IP
administration. Here, using synchrotron radiation X-ray fluorescence spectrometry
(SR-XRF) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP
MS), Pt distribution and penetration in OC peritoneal xenografts were determined
at nanometer scale after IP chemoperfusion of cisplatin at 37-38 degrees C or 40
41 degrees C (hyperthermic). Using principal component analysis (PCA) the
presence of phosphorus, manganese, calcium, zinc, iron, bromine, and sulfur was
correlated with the distribution of Pt, while k-means analysis was used to
quantify the amount of Pt in weight% in tumor stroma and in tumor cells. The
results showed a heterogeneous distribution of Pt throughout the tumor, with an
accumulation in the extracellular matrix. LA-ICP-MS mappings indicated
significantly higher concentrations of Pt (P=0.0062) after hyperthermic
chemoperfusion of cisplatin, while SR-XRF demonstrated a deeper tissue Pt
penetration after hyperthermic treatment. Using PCA, it was showed that Pt co
localizes with bromine and sulfur. No differences were observed in Pt
distribution regarding tumor cells and stroma, when comparing normo- vs.
hyperthermic treatment. In conclusion, SR-XRF and LA-ICP-MS are suitable and
highly sensitive techniques to analyze the penetration depth and distribution of
Pt-based drugs after IP administration. To the best of our knowledge, this is the
first experiment in which the distribution of Pt is analyzed at the cellular
level after IP administration of cisplatin.
PMID- 27611098
TI - Authentication of Schisandra chinensis and Schisandra sphenanthera in Chinese
patent medicines.
AB - Authentication of species is crucial for ensuring the safety and efficacy of
herbal medicines. The fruits of Schisandra chinensis and S. sphenanthera have
been used for the same traditional Chinese drug, Wuweizi, but are found to be
quite different according to their constituents, pharmacological effects, and
qualities. These two fruits have been recorded as Schisandrae Chinensis Fructus
(Wuweizi) and Schisandrae Sphenantherae Fructus (Nan-wuweizi), respectively, by
Chinese Pharmacopoeia, 2000 edition. However, Nan-wuweizi is often found to be
taken as Wuweizi in some Chinese patent drugs intentionally or by mistake because
of its lower price and similar characteristics to Wuweizi. In this study, the
selection and validation of special chemical markers for the identification of
Schisandra species were established by HPLC-DAD-MS profiling analysis. Simple TLC
and HPLC methods were proposed for the accurate determination of Nan-wuweizi from
Wuweizi in Chinese patent medicines, using schisandrin and anwulignan as the
identifying markers for Wuweizi and Nan-wuweizi, respectively. Through the
establishment of a statistical model, adulterated or misused ratios of Nan
wuweizi in Wuweizi (w/w), as well as in Fenghan Kesou pills, can be determined.
The limit of detection of Nan-wuweizi in a mixture (w/w) using both TLC and HPLC
methods is 5% (mixed crude drugs of 50mg and 5g in a 1000g prescribed amount).
The constructed statistical model relating the HPLC peak area ratio
(anwulignan/schisandrin) and adulteration ratio is suitable for mixed crude drugs
and Fenghan Kesou pills, and the two fitting equations have a good correlation
(r=0.9979). Furthermore, 36 commercial Chinese patent medicines containing
Wuweizi or Nan-wuweizi according to their labels were checked by these methods,
and Nan-wuweizi was detected in Renshen Wuweizi Granules and Fenghan Kesou Pills.
The ratios of Nan-wuweizi in these mixtures (w/w) were 100:0 for both, which does
not comply with the statutory prescription. This study provided a simple and
reliable method to prevent the adulteration or misuse of Nan-wuweizi in crude
drugs and patent medicines of Wuweizi.
PMID- 27611099
TI - Characterization of forced degradation products of clozapine by LC-DAD/ESI-Q-TOF.
AB - Forced degradation of clozapine in solutions under acidic, basic, neutral, photo
UV-vis, photo UVC and oxidative stress conditions was investigated and structural
elucidation of its degradation products was performed with the use of the UHPLC
DAD system coupled with accurate hybrid ESI-Q-TOF mass spectrometer. The
developed method allows to collect all essential data for the determination of
degradation kinetics and for the structural elucidation of the formed products.
Six degradation products were found and their masses and formulas were obtained
with high accuracy (0.61-3.75ppm). For all the analyzed compounds MS/MS
fragmentation spectra were also obtained allowing structural elucidation of the
unknown degradation products. It was found that the decomposition of clozapine
yields the first-order kinetic reaction in all stress conditions and it is
fragile towards acidic hydrolysis and oxidative conditions. Additionally, PCA
analysis of registered TOF (MS) forced degradation profiles of clozapine shows no
differences between the samples obtained from pharmaceutical formulation and bulk
substance.
PMID- 27611100
TI - Investigation on Raman spectral features of a coated tablet under variation of
its orientation respective to laser illumination and measurement of nominal
coating thickness of packed tablets.
AB - To investigate Raman spectral features of a coated biconvex tablet under
variation of its orientation respective to laser illumination, spectra of the
tablet were collected by illuminating laser on 12 different locations on the
tablet with 3 different illumination angles of 45, 75 and 90 degrees . The
spectral variations were more substantial when the tablet faces with engraved
letters and greater surface curvature were measured, since the sampled volume of
coating relative to that of a core tablet changed significantly under these
circumstances as the illumination angle varied. The preliminary examination
confirmed that the acquisition of tablet-representative spectra was the requisite
for reliable measurement of coating thickness. Then, to mimic real monitoring of
coating process, Raman spectra were directly collected on a packing of 30 tablets
with repetition of random tablet packing up to 15 times and univariate models
utilizing the intensity of coating peak at 638cm-1 were developed using the
cumulatively averaged spectra with an average weight of the 30 tablets as a
reference. To acquire less tablet orientation-sensitive spectra, a wide area
illumination (WAI) scheme providing a large sampling area (28.3mm2) on a tablet
with a long focal length (~25cm) was employed. The averaging of the first to
seventh spectra, equivalently utilizing more packing-representative spectra for
quantitative analysis, made the measurement of nominal coating thickness of
packed tablets accurate.
PMID- 27611103
TI - Do code of conduct audits improve chemical safety in garment factories? Lessons
on corporate social responsibility in the supply chain from Fair Wear Foundation.
AB - BACKGROUND: In managing chemical risks to the environment and human health in
supply chains, voluntary corporate social responsibility (CSR) measures, such as
auditing code of conduct compliance, play an important role. OBJECTIVES: To
examine how well suppliers' chemical health and safety performance complies with
buyers' CSR policies and whether audited factories improve their performance.
METHODS: CSR audits (n = 288) of garment factories conducted by Fair Wear
Foundation (FWF), an independent non-profit organization, were analyzed using
descriptive statistics and statistical modeling. RESULTS: Forty-three per cent of
factories did not comply with the FWF code of conduct, i.e. received remarks on
chemical safety. Only among factories audited 10 or more times was there a
significant increase in the number of factories receiving no remarks.
CONCLUSIONS: Compliance with chemical safety requirements in garment supply
chains is low and auditing is statistically correlated with improvements only at
factories that have undergone numerous audits.
PMID- 27611101
TI - Differential neurogenic effects of casein-derived opioid peptides on neuronal
stem cells: implications for redox-based epigenetic changes.
AB - Food-derived peptides, such as beta-casomorphin BCM7, have potential to cross the
gastrointestinal tract and blood-brain barrier and are associated with
neurological disorders and neurodevelopmental disorders. We previously
established a novel mechanism through which BCM7 affects the antioxidant levels
in neuronal cells leading to inflammatory consequences. In the current study, we
elucidated the effects of casein-derived peptides on neuronal development by
using the neurogenesis of neural stem cells (NSCs) as an experimental model.
First, the transient changes in intracellular thiol metabolites during NSC
differentiation (neurogenesis) were investigated. Next, the neurogenic effects of
food-derived opioid peptides were measured, along with changes in intracellular
thiol metabolites, redox status and global DNA methylation levels. We observed
that the neurogenesis of NSCs was promoted by human BCM7 to a greater extent,
followed by A2-derived BCM9 in contrast to bovine BCM7, which induced increased
astrocyte formation. The effect was most apparent when human BCM7 was
administered for 1day starting on 3days postplating, consistent with
immunocytochemistry. Furthermore, neurogenic changes regulated by bovine BCM7 and
morphine were associated with an increase in the glutathione/glutathione
disulfide ratio and a decrease in the S-adenosylmethionine/S-adenosylhomocysteine
ratio, indicative of changes in the redox and the methylation states. Finally,
bovine BCM7 and morphine decreased DNA methylation in differentiating NSCs. In
conclusion, these results suggest that food-derived opioid peptides and morphine
regulated neurogenesis and differentiation of NSCs through changes in the redox
state and epigenetic regulation.
PMID- 27611104
TI - Prospective Controlled Study of Gastroesophageal Reflux in Dogs with Naturally
Occurring Laryngeal Paralysis.
AB - OBJECTIVE: To determine the frequency, nature, and magnitude of gastroesophageal
reflux (GER) in dogs with laryngeal paralysis (LP). STUDY DESIGN: Prospective
comparative clinical study. ANIMALS: Client-owned dogs with LP and healthy client
owned dogs (n = 6 each). METHODS: Dogs underwent sedated laryngeal examination
for diagnosis and grading of bilateral LP and for placement of a nasoesophageal
dual pH/impedance probe. Endoscopy was used to confirm probe location and
evaluate the distal esophagus. Data were recorded continuously. GER was defined
as pH<4 or >7.5 lasting >2 seconds reaching a magnitude of 2 impedance sensors
proximally. RESULTS: The median total number of GER events per hour was 0.64
(range, 0.44-1.6) for the LP group and 0.53 (range, 0.38-1.0) for the control
group (P = 0.259; power = 0.50). The median total number of alkaline
regurgitation events per hour was 0.37 (range, 0.17-0.93) for the LP group and
0.46 (range, 0.25-1.0) for control group (P = 0.575; power = 0.57). The median
total number of acidic regurgitation events per hour was 0.22 (range, 0-0.70) and
0.0 (range, 0-0.14) for the LP and control groups, respectively (P = 0.025).
Acidic reflux events reached the proximal pH sensor in 2 dogs in the LP group for
a total of 4 reflux events and in 1 dog in the control group for a total of 3
reflux events (P = 0.673). CONCLUSION: Based on the limited number of dogs
studied, it appears that dogs with naturally occurring LP have increased acidic
reflux events compared to clinically normal dogs. GER can reach the most proximal
part of the esophagus.
PMID- 27611102
TI - Diets enriched in whey or casein improve energy balance and prevent morbidity and
renal damage in salt-loaded and high-fat-fed spontaneously hypertensive stroke
prone rats.
AB - High-fat diets induce obesity and increase risks of diabetes and cardiovascular
and renal disorders. Whey- or casein-enriched diets decrease food intake and
weight gain; however, their cardiovascular and renal benefits are unclear. We
determined whether whey- and casein-enriched diets improve energy balance and are
protective against renal damage and morbidity associated with stroke in an
obesogenic and hypertensive experimental setting. We also assessed whether the
hypophagic effects of these diets were due to reduced diet preference. In
experiment 1, spontaneously hypertensive stroke-prone rats were randomized to (a)
control (CON; 14% kcal protein, 33% fat), (b) whey (WHY; 40% protein, 33% fat),
(c) casein (CAS; 40% protein, 33% fat) or (d) chow (CHW; 24% protein, 13% fat)
for 12 weeks with 1% salt in drinking water for CON, WHY and CAS groups. Our
results demonstrated that both WHY and CAS produced short-term hypophagia,
moderately increased energy expenditure and decreased respiratory quotient, body
weight and lean mass, with effects of WHY being more prolonged. Further, only WHY
decreased fat mass and blood pressure. Importantly, both WHY and CAS prevented
morbidity associated with stroke and decreased indices of renal inflammation
(tumor necrosis factor-alpha, interleukin-6) and damage (osteopontin, renal
lesions). In experiment 2, following four initial conditioning trials, the
preference for CON, WHY or CAS diet was determined. Both WHY and CAS decreased
food intake during conditioning and decreased preference. In conclusion, diets
enriched in whey or casein improved energy balance, increased survival and
prevented renal damage in salt-loaded and high-fat-fed spontaneously hypertensive
stroke-prone rats.
PMID- 27611105
TI - Identification of genes and proteins associated with anagen wool growth.
AB - Identifying genes of major effect for wool growth would offer strategies for
improving the quality and increasing the yield of fine wool. In this study, we
employed the Agilent Sheep Gene Expression Microarray and proteomic technology to
investigate the gene expression patterns of body side skin (more wool growing) in
Aohan fine wool sheep (a Chinese indigenous breed) in comparison with groin skin
(no wool growing) at the anagen stage of the wool follicle. A microarray study
revealed that 4772 probes were differentially expressed, including 2071
upregulated and 2701 downregulated probes, in the comparisons of body side skin
vs. groin skin (S/G). The microarray results were verified by means of
quantitative PCR. A total of 1099 probes were assigned to unique
genes/transcripts. The number of distinct genes/transcripts (annotated) was 926,
of which 352 were upregulated and 574 were downregulated. In S/G, 13 genes were
upregulated by more than 10 fold, whereas 60 genes were downregulated by more
than 10 fold. Further analysis revealed that the majority of the genes possibly
related to the wool growth could be assigned to categories including regulation
of cell division, intermediate filament, cytoskeletal part and growth factor
activity. Several potential gene families may participate in hair growth
regulation, including fibroblast growth factors, transforming growth factor-beta,
WNTs, insulin-like growth factor, vascular endothelial growth factors and so on.
Proteomic analysis also revealed 196 differentially expressed protein points, of
which 121 were identified as single protein points.
PMID- 27611106
TI - Detection of Renal Stones on Portal Venous Phase CT: Comparison of Thin Axial and
Coronal Maximum-Intensity-Projection Images.
AB - OBJECTIVE: The objective of our study was to determine the sensitivity of thin
axial and coronal maximum-intensity-projection (MIP) images for the detection of
renal stones on contrast-enhanced CT performed in the portal venous phase.
MATERIALS AND METHODS: This retrospective study included 72 patients, 59 of whom
had at least one renal stone, who underwent unenhanced CT immediately followed by
contrast-enhanced CT in the portal venous phase. Two abdominal imaging fellowship
trained radiologists independently recorded the number of stones on both thin (1
1.50 mm) axial and 5-mm coronal MIP images in the portal venous phase. The
reference standard was determined by consensus review of the thin axial
unenhanced images. Reviewer sensitivity was calculated and categorized by stone
diameter. RESULTS: One hundred forty-eight stones were present; the mean number
of stones per patient was 2.5 (SD, 2.7). The mean stone size was 2.5 mm (SD,
2.7). The sensitivity of thin axial images was 89.9%, 99.0%, and 100.0% for
reviewer 1 and 83.1%, 98.0%, and 100.0% for reviewer 2 for all stones, stones >=
2 mm, and stones >= 3 mm, respectively. The sensitivity of coronal MIP images was
86.5%, 96.2%, and 100.0% for reviewer 1 and 79.0%, 91.4%, and 96.6% for reviewer
2 for all stones, stones >= 2 mm, and stones >= 3 mm, respectively. CONCLUSION:
Thin axial images are highly sensitive for the detection of renal stones >= 2 mm
on portal venous phase CT. Coronal MIP images do not improve renal stone
detection over thin axial images.
PMID- 27611107
TI - Effects of FOXJ2 on TGF-beta1-induced epithelial-mesenchymal transition through
Notch signaling pathway in non-small lung cancer.
AB - As one member of Forkhead box transcription factors, Forkhead box J2 (FOXJ2) has
been found to be involved in epithelial-mesenchymal transition (EMT) process.
However, the role and mechanism of FOXJ2 in non-small cell lung cancer (NSCLC)
and EMT regulation have not been fully revealed. In this paper, it was revealed
that the expression of FOXJ2 was lower in NSCLC samples compared with matched
peritumoral lung tissue. We demonstrated that FOXJ2 expression was down-regulated
by transforming growth factor-beta1 (TGF-beta1) treated, and overexpression of
FOXJ2 inhibited TGF-beta1-induced EMT. Mechanistically, knocking out the
expression of FOXJ2 promoted EMT by increasing the expression of Notch1 and NICD.
This study implicates the potential value of FOXJ2 as a molecular marker for
NSCLC.
PMID- 27611108
TI - Immediate versus delayed treatment for recently symptomatic carotid artery
stenosis.
AB - BACKGROUND: The timing of surgery for recently symptomatic carotid artery
stenosis remains controversial. Early cerebral revascularization may prevent a
disabling or fatal ischemic recurrence, but it may also increase the risk of
hemorrhagic transformation, or of dislodging a thrombus. This review examined the
randomized controlled evidence that addressed whether the increased risk of
recurrent events outweighed the increased benefit of an earlier intervention.
OBJECTIVES: To assess the risks and benefits of performing very early cerebral
revascularization (within two days) compared with delayed treatment (after two
days) for people with recently symptomatic carotid artery stenosis. SEARCH
METHODS: We searched the Cochrane Stroke Group Trials Register in January 2016,
the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library
2016, Issue 1), MEDLINE (1948 to 26 January 2016), EMBASE (1974 to 26 January
2016), LILACS (1982 to 26 January 2016), and trial registers (from inception to
26 January 2016). We also handsearched conference proceedings and journals, and
searched reference lists. There were no language restrictions. We contacted
colleagues and pharmaceutical companies to identify further studies and
unpublished trials. SELECTION CRITERIA: All completed, truly randomized trials
(RCT) that compared very early cerebral revascularization (within two days) with
delayed treatment (after two days) for people with recently symptomatic carotid
artery stenosis. DATA COLLECTION AND ANALYSIS: We independently selected trials
for inclusion according to the above criteria, assessed risk of bias for each
trial, and performed data extraction. We utilized an intention-to-treat analysis
strategy. MAIN RESULTS: We identified one RCT that involved 40 participants, and
addressed the timing of surgery for people with recently symptomatic carotid
artery stenosis. It compared very early surgery with surgery performed after 14
days of the last symptomatic event. The overall quality of the evidence was very
low, due to the small number of participants from only one trial, and missing
outcome data. We found no statistically significant difference between the
effects of very early or delayed surgery in reducing the combined risk of stroke
and death within 30 days of surgery (risk ratio (RR) 3.32; confidence interval
(CI) 0.38 to 29.23; very low-quality evidence), or the combined risk of
perioperative death and stroke (RR 0.47; CI 0.14 to 1.58; very low-quality
evidence). To date, no results are available to confirm the optimal timing for
surgery. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence
available to support either very early or delayed cerebral revascularization
after a recent ischemic stroke. Hence, further randomized trials to identify
which patients should undergo very urgent revascularization are needed. Future
studies should stratify participants by age group, sex, grade of ischemia, and
degree of stenosis. Currently, there is one ongoing RCT that is examining the
timing of cerebral revascularization.
PMID- 27611109
TI - Effect of urea supplementation on performance and safety in diets of Dorper
crossbred sheep.
AB - This study was conducted to evaluate the efficacy and safety of dietary urea in
sheep rations having a 50:50 concentrate:roughage ratio. Sixty-four Dorper * thin
tailed Han crossbred ram lambs with an average body weight of 30.8 (+/-0.02) kg
were randomly divided into four groups of 16 sheep each, and each group was fed
one of the following diets: a basal diet (CON), or CON supplemented with 0.5%
(0.5UTM), 1.5% (1.5UTM) or 2.5% (2.5UTM) urea. Growth performance, carcass
characteristics, non-carcass offals, meat quality and peptic tissue lesions were
assayed. The average daily weight gains for CON, 0.5UTM, 1.5UTM and 2.5UTM were
216, 218, 200 and 170 g, respectively, with the CON and 0.5UTM groups higher than
2.5UTM group (p < 0.05). Sheep from the 2.5UTM treatment had a significantly
lower dry matter intake (1.29 kg/day) than those from the CON and 0.5UTM
treatments (1.42 and 1.43 kg/day, p < 0.05), and the feed conversion ratio in the
2.5UTM group was the highest (p < 0.05). Carcass characteristics, including
shrunk body weight, empty body weight, hot carcass weight, dress percentage, and
the absolute or relative weight (% body weight) of heart, liver, spleen, lung and
kidney, were not altered by the treatments (p > 0.05). The muscular pH of 2.5UTM
was higher than that of CON (5.68 vs. 5.52, p < 0.05), and shear force in 0.5UTM
was lower compared with CON and 2.5UTM (p < 0.05). The anatomical structure
lesions in kidneys became more serious with the increasing dietary urea
concentrations, with the 2.5UTM animals showing the most severe lesions compared
with CON animals. Therefore, supplementary urea as a non-protein nitrogen source
for sheep should not exceed 1.5% of ration having a 50:50 concentrate:roughage
ratio to ensure efficacy and safety.
PMID- 27611110
TI - Autonomic influence on atrial fibrillatory process: head-up and head-down
tilting.
AB - BACKGROUND: Changes in the autonomic nervous system (ANS) tone are present
before, during, and after episodes of atrial fibrillation (AF). Atrial
fibrillatory rate (AFR, the inverse of the atrial cycle length) has been used as
a surrogate marker for local refractoriness and is a key characteristic of the
fibrillatory process in patients with AF. Aim of this study is to assess changes
in AFR, as an effect of autonomic balance change. METHODS: Forty patients
undergoing cardiac cardioversion for symptomatic persistent AF were included in
the study. Surface ECG was recorded during rest, head-down (HDT, -30 degrees ),
and head-up tilt (HUT, +60 degrees ). A median value of AFR was computed in each
phase of the protocol. RESULTS: AFR decreased during HDT compared to the baseline
(B) condition in all patients but three (median AFR_B = 391 fpm vs. AFR_HDT = 377
fpm, p < .0001). HUT increased AFR, making it significantly higher than HDT and
baseline conditions (median AFR_HUT = 396 fpm, p < .0001 vs. B and HDT). Heart
rate (HR) increased during HUT, but had a heterogeneous behavior in the
population during HDT: about one third of the patients had an HR lower during HDT
than during baseline, whereas the remaining two third had an increase in HR
during HDT. CONCLUSIONS: Dominant sympathetic/vagal tone during HUT/HDT
significantly affects AFR, increasing/decreasing in respect to baseline. It may
be worth exploring the possibility that patients with AF of shorter duration can
convert to sinus rhythm during HDT.
PMID- 27611111
TI - Conversion of Dinitrogen to Nitriles at a Multinuclear Titanium Framework.
AB - Activation and functionalization of N2 : A mixed diimide/dinitride tetranuclear
titanium complex formed by activation of dinitrogen served as a unique platform
for the synthesis of nitriles. Functional groups such as aromatic C-X (X=Cl, Br,
I) bonds, nitro groups, and ammonia-sensitive aldehyde and chloromethyl moieties
were compatible with the synthetic method.
PMID- 27611112
TI - Unmasking the enterprising nurse: migrant care workers and the discursive
mobilisation of productive professionals.
AB - Public care work organisations in Northern Europe often seek to increase their
economic efficiency in ways that care workers criticise for reducing both their
professional autonomy and the quality of care. Recently, the ideal of
'enterprising nursing' has emerged as a political belief according to which
economic efficiency, care workers' autonomy and the quality of care can be
improved in tandem by cultivating care workers' agential abilities. This article
examines the reception of this belief among migrant care workers in Finland.
Drawing on research interviews, the analysis demonstrates how migrant care
workers may have difficulties in aligning themselves with the enterprising ideals
but also in protesting them. Ethnicity, and the status of a migrant, can offer
resources for both constructing enterprising subjectivities and reframing care
workers' agency, and their organisational environment, in more critical terms.
PMID- 27611113
TI - The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic
Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological
Conditions.
AB - The phenolic hydroxyl group of tyrosine residue plays a crucial role in the
structure and function of many proteins. However, little study has been reported
about its modification by chemical agents under physiological conditions. In this
study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can
be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other
polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid
metabolites of polyhalogenated aromatic compounds. The modification was found to
be mainly due to the formation of a variety of fluoroquinone-O-tyrosine
conjugates and their hydroxylated derivatives via nucleophilic substitution
pathway. Analogous modifications were observed for tyrosine-containing peptides.
Further studies showed that the blockade of the reactive phenolic hydroxyl group
of tyrosine in the substrate peptide, even by very low concentration of
tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine
phosphorylation. This is the first report showing the exceptionally facile
chemical modification of the phenolic hydroxyl group of tyrosine by
polyhalogenated quinones under normal physiological conditions, which may have
potential biological and toxicological implications.
PMID- 27611114
TI - Atrial fibrillation, anticoagulant stroke prophylaxis and bleeding risk with
ibrutinib therapy for chronic lymphocytic leukaemia and lymphoproliferative
disorders.
PMID- 27611115
TI - An initial report on the intraoperative use of indocyanine green fluorescence
imaging in the surgical management of liver tumorss.
AB - BACKGROUND: There has been a recent interest in the use of Indocyanine green
(ICG) imaging. The aim of this study is to review our initial experience in liver
surgery. METHODS: ICG fluorescent imaging was used in 15 patients undergoing
surgical treatment of their liver tumors between 2015 and 2016. ICG imaging was
initially performed, followed by intraoperative ultrasound (IOUS). Findings on
fluorescence were compared with preoperative cross-sectional imaging and IOUS.
RESULT: Sixty-two lesions were identified, with 34 located superficially and 28
deeply in the liver. While 13 patients underwent surgery for malignant liver
metastases, two patients had operations for benign liver diseases. Seven patients
underwent open or robotic liver resections, five laparoscopic microwave liver
ablation, and three diagnostic laparoscopy. ICG identified all of the superficial
lesions. IOUS identified 98% of all lesions. The most benefit of ICG was in
showing the margins of the superficial lesions in real-time and guiding surgical
treatment, which was limited by IOUS. CONCLUSION: This is the first North
American study to evaluate the potential utility of ICG during liver surgery. Its
major benefit seems to be in providing real-time feedback to the surgeon about
the margins of superficial tumors for resection or ablation. J. Surg. Oncol.
2016;114:625-629. (c) 2016 Wiley Periodicals, Inc.
PMID- 27611116
TI - Emotional eating and in vivo norepinephrine transporter availability in obesity:
A [11 C]MRB PET pilot study.
AB - OBJECTIVE: Emotional eating (EE) has been linked to norepinephrine dysfunction.
Therefore, we aimed to investigate the relationship between EE and norepinephrine
transporter (NET) availability. METHOD: Ten severely obese individuals (body mass
index (BMI) 42.4 +/- 3.7 kg/m2 ) and ten non-obese, healthy controls (BMI 23.9 +/
2.5 kg/m2 ) matched for age and sex were studied using (S,S)-[11 C]-O
methylreboxetine ([11 C]MRB) positron emission tomography (PET). Kinetic modeling
of regional tissue time activity curves was performed using multilinear reference
tissue model 2 (MRTM2, with the occipital cortex as a reference region) to
estimate binding potential based on individual PET-MR coregistration. To test for
associations of EE and NET availability, participants completed the EE subscale
of the Dutch Eating Behavior Questionnaire before scanning. RESULTS: Obese
individuals and non-obese, healthy controls did not significantly differ
regarding EE scores and regional NET availability. For obese individuals only,
correlative data analyses pointed to a sinoidal distribution pattern as a higher
degree of EE related to lower NET availability in the locus coeruleus and to
higher NET availability in the left thalamus. DISCUSSION: These results indicate
that central in vivo NET availability is altered in EE of individuals with
obesity. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:152-156).
PMID- 27611117
TI - "Post-thrombotic panic syndrome": A thematic analysis of the experience of venous
thromboembolism.
AB - OBJECTIVES: Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and
pulmonary embolism [PE]) is a serious, potentially traumatic, life-threatening
condition and a major cause of mortality and morbidity. The aim of this study was
to explore the patients' experiences of VTE and its psychosocial impact. METHODS:
Audio-recorded semistructured interviews with a purposive sample of 12
participants who had experienced a first-time DVT or PE within the previous 6
months. Interviews were transcribed and thematically analysed. RESULTS: Four key
themes with 10 subthemes were identified. The major themes were as follows: VTE
as life-changing and traumatic, living with uncertainty and fear of reoccurrence,
feeling let down by health services, and positive changes and outcomes. The
content of themes varied according to age at the time of VTE and participants'
experiences of diagnosis and treatment. CONCLUSIONS: The data demonstrate the
psychosocial impact of VTE as life-changing, encompassing a dynamic duality of
trauma and growth. The findings highlight a potential role for health care
professionals in identifying and supporting individuals at risk of post-traumatic
stress, and targeted interventions to enhance psychological well-being and
recovery and reduce distress. Statement of contribution What is already known on
this subject? Venous thromboembolism (VTE) is often characterized by sudden onset
and may carry a significant threat to life, particularly in the form of pulmonary
embolism. Early studies suggest that health-related quality of life is negatively
affected by VTE and there is likely to be a high prevalence of trauma. What does
this study add? This study explores for the first time the experience of, and
reactions to, VTE in the 6 months following its occurrence. It explores the role
that psychological well-being can play in recovery after VTE. This study
highlights that improvements are needed to support VTE patients to cope with the
emotional impact of VTE. A dual process of trauma and post-traumatic growth after
VTE is reported for the first time.
PMID- 27611118
TI - Simultaneous improvement and worsening of vitiligo lesions during the course of
NB-UVB phototherapy; vitiligo may not act as one unit.
AB - Re-pigmentation and stabilization are the two ultimate goals of any re-pigmenting
plan designed for vitiligo management. Furthermore, whether the improvement of
some vitiligo lesions could be considered a guarantee for a similar response
and/or stabilization of the rest of the lesions or not, remains to be clarified.
To evaluate the behavior of non-segmental vitiligo (NSV), while on narrow band
ultraviolet B (NB-UVB) phototherapy. 25 patients with stable generalized NSV were
included and received NB-UVB twice weekly. For the sake of ensuring accuracy of
follow up, up to four lesions were randomly chosen in each patient and regularly
measured using the point counting technique. The over-all point counting
technique of all included patients showed a significant reduction (18.5 +/- 8.4
cm2 to 8.2+/- 3.1 cm2 ) after 6 months of therapy (p < .001). Nine patients
(36%), showed mixed response in the different lesions. Improvement was documented
in some lesions, while other lesions showed no response or even worsening. No
significant correlations were detected between the behavior of vitiligo during NB
UVB and any of the demographic or clinical data of the patients. NB-UVB is a
pillar in the management of vitiligo, however close follow-up of the patient as a
whole and his lesions, by both subjective and objective measures are mandatory to
detect activity as early as possible, as vitiligo at many times may not act as
one unit. This early detection of activity and the subsequent change in the
treatment policy may ultimately change the final outcome of treatment.
PMID- 27611174
TI - Hydrogen Storage Performance in Pd/Graphene Nanocomposites.
AB - We have developed a Pd-graphene nanocomposite for hydrogen storage. The
spherically shaped Pd nanoparticles of 5-45 nm in size are homogeneously
distributed over the graphene matrix. This new hydrogen storage system has
favorable features like desirable hydrogen storage capacity, ambient conditions
of hydrogen uptake, and low temperature of hydrogen release. At a hydrogen
charging pressure of 50 bar, the material could yield a gravimetric density of
6.7 wt % in the 1% Pd/graphene nanocomposite. As we increased the applied
pressure to 60 bar, the hydrogen uptake capacity reached 8.67 wt % in the 1%
Pd/graphene nanocomposite and 7.16 wt % in the 5% Pd/graphene nanocomposite. This
system allows storage of hydrogen in amounts that exceed the capacity of the
gravimetric target announced by the U.S. Department of Energy (DOE).
PMID- 27611173
TI - Elevated Levels of T-helper 17-associated Cytokines in Diabetes Type I Patients:
Indicators for Following the Course of Disease.
AB - BACKGROUND: Type 1 diabetes (T1D) is thought to involve chronic inflammation,
which is manifested by the activation and expression of different inflammatory
mediators. Th1- and Th17-associated cytokines are factors that have been shown to
exert profound pro-inflammatory activities and have been implicated in the
pathogenesis of T1D in mice and humans. OBJECTIVES: Therefore, the aim of this
case control study was to determine the serum level of IL-17, IL-21, IL-27,
transforming growth factor beta (TGF-beta), and IFN-gamma and their reciprocal
relationship in Iranian T1D patients. PATIENTS AND METHODS: Blood samples were
collected from 48 T1D patients and 49 healthy individuals with no history of
malignancies or autoimmune disorders based on simple sampling. The serum levels
of IL-17, IL-21, IL-27, TGF-beta, and IFN-gamma were measured by the enzyme
linked immunosorbent assay (ELISA). RESULTS: The serum levels of IL-17 and IL-21
were significantly higher in T1D patients compared to the healthy individuals (p
= 0.005 and 0.01, respectively), but interestingly, the opposite was the case for
IL-27 (p < 0.0001). However, there were no significant differences in TGF-beta
and IFN-gamma between both groups. In addition, IL-17/IFN-gamma and IL-17/IL-27
ratios were higher in patients compared to the control group. CONCLUSIONS: Our
results indicated dominant Th17-associated IL-17, suggesting a shift from the
Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote
inflammation in beta cells in T1D. In addition, it suggests the role of Th17 and
Th17/Th1 ratios as a potential contributor to beta cells destruction and the
Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis
before the destruction of beta cells and progression of the disease to the
clinical end stages.
PMID- 27611175
TI - Extract of Ganoderma formosanum Mycelium as a Highly Potent Tyrosinase Inhibitor.
AB - In this study, the inhibitory effect of Ganoderma formosanum mycelium extracts on
tyrosinase, the central regulatory enzyme being responsible for cutaneous
pigmentation, was investigated in both cell-free and cellular enzymatic systems,
as well as in phenotype-based zebrafish model. Bioassay-guided purification
indicated that the ethyl acetate fraction of G. fromosanum mycelium ethanolic
extract (GFE-EA) demonstrated the highest inhibition toward cell-free tyrosinase
(IC50 = 118.26 +/- 13.34 ppm). The secreted and intracellular melanin of B16-F10
cells were reduced by GFE-EA through suppression of tyrosinase activity (IC50 =
102.27 +/- 9.49 ppm) and its protein expression. Moreover, GFE-EA decreased
surface pigmentation level of zebrafish via down-regulation of tyrosinase
activity. Most of all, there is no significant difference in morphology and
mortality between control and GFE-EA treated groups. Not only does GFE-EA exhibit
similar depigmenting efficacy to kojic acid with lower dosage (approximately one
seventh of dose), but show less toxicity to zebrafish. It is worth noting that
GFE-EA is extracted from mycelium, which subverts the general concept that
mycelium lacks certain bioactivities possessed by fruit bodies. Altogether, it
would appear that GFE-EA has great potential for application in the cosmetics
industry.
PMID- 27611177
TI - Effects of maternal postpartum depression in a well-resourced sample: Early
concurrent and long-term effects on infant cognitive, language, and motor
development.
AB - This study examined early and long-term effects of maternal postpartum depression
on cognitive, language, and motor development in infants of clinically depressed
mothers. Participants were 83 mothers and their full-term born children from the
urban region of Copenhagen, Denmark. Of this group, 28 mothers were diagnosed
with postnatal depression three to four months postpartum in a diagnostic
interview. Cognitive, language, and motor development was assessed with the
Bayley Scales of Infant and Toddler Development third edition, when the infants
were 4 and 13 months of age. We found that maternal postpartum depression was
associated with poorer cognitive development at infant age four months, the
effect size being large (Cohen's d = 0.8) and with similar effects for boys and
girls. At 13 months of age infants of clinical mothers did not differ from
infants of non-clinical mothers. At this time most (79%) of the clinical mothers
were no longer, or not again, depressed. These results may indicate that maternal
depression can have an acute, concurrent effect on infant cognitive development
as early as at four months postpartum. At the same time, in the absence of other
risk factors, this effect may not be enduring. The main weaknesses of the study
include the relatively small sample size and that depression scores were only
available for 35 of the non-clinical mothers at 13 months.
PMID- 27611176
TI - Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with
resveratrol.
AB - Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in
a variety of human cancers by triggering mitochondria apoptosis pathway and
autophagy. However, there are scarcely reports on its apoptosis-promoting effect
in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we
investigated the underlying mechanism and apoptosis-inducing effects of
resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA)
rats. Since using resveratrol for 12 days resulted in a significant decreasing
the swelling degree of the paw, reducing malondialdehyde (MDA) content and
enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione
peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5
MUMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein
expression in FLSs. But, resveratrol could reverse these effects by changing
mitochondrial membrane potential (Deltapsim) to promote mitochondrial reactive
oxygen species (mtROS) generation in 5 MUMH2O2-treatment FLSs. These results
suggest that oxidative stress existed in AA rats. Resveratrol could suppress
oxidative stress in AA rats and increase mtROS production by reducing autophagy
protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the
apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of
resveratrol confers patients with rheumatoid arthritis.
PMID- 27611178
TI - Cutaneous involvement of pre-existing Rosai-Dorfman disease via post-herpetic
isotopic response.
AB - We report the case of a patient with a long-standing history of extranodal, sinus
histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and no
evidence of original cutaneous involvement as well as a history of herpes zoster
of the left flank with post-herpetic neuralgia who went on to develop multiple,
round-to-oval, red-brown, atrophic macules and thin papules at the sites of
herpes zoster scars on the left flank. Histopathology showed a dense nodular
infiltrate of lymphocytes with some plasma cells and numerous large pale-staining
histiocytes (S100+/CD68+), consistent with Rosai-Dorfman disease. This case
showed exclusively cutaneous involvement, as demonstrated by otherwise normal
physical examination, laboratory evaluation and imaging. This is the second
reported case of Rosai-Dorfman disease occurring at the site of zoster scars, and
to our knowledge this represents the first case report of cutaneous involvement
of pre-existing Rosai-Dorfman disease via post-herpetic isotopic response (Wolf's
isotopic response).
PMID- 27611179
TI - Testicular function during puberty and young adulthood in patients with
Klinefelter's syndrome with and without spermatozoa in seminal fluid.
AB - Patients with Klinefelter's syndrome experience progressive testicular
degeneration resulting in impaired endocrine function and azoospermia. What
proportion of adolescents develop testosterone deficiency during puberty and how
many have spermatozoa in their semen is unclear to date. We aimed to investigate
testicular function during puberty and young adulthood in patients with
Klinefelter's syndrome and to assess testosterone effects in target tissues. The
clinical data of 281 patients with non-mosaic Klinefelter's syndrome aged 10-25
years without previous testosterone replacement were reviewed. In late pubertal
adolescents, semen analyses were evaluated, and testicular volumes, hormone and
haemoglobin (Hb) levels, the number of CAG repeats and final height data were
compared to those of 233 age-matched controls with pubertal gynaecomastia.
Spontaneous pubertal virilisation to Tanner stages IV-V occurred. Serum T levels
>=10 nmol/L were reached in 62% of patients with Klinefelter's syndrome and in
85% of controls at ages 15-25 (TKFS : 12.2 +/- 5.4 vs. TC : 16.6 +/- 7.2 nmol/L).
LHKFS levels were elevated >10 U/L in 84%, and normal in all controls (LHKFS :
18.6 +/- 12.2 vs. LHC : 3.5 +/- 1.6 U/L). In nine of 130 (7%) adolescents with
Klinefelter's syndrome, spermatozoa (oligozoospermia) were found in semen; all
had T levels >7 nmol/L and eight of nine had LH levels <=18 U/L, while their
hormone levels, number of CAG repeats and testicular volumes were not different
from those of adolescents with azoospermia. Controls had normal sperm
concentrations in 73% (46/63). Semen volumesKFS were normal in 55% vs. 78% in
controls; HbKFS was normal in 89% (HbC : 97%). Mean final heightKFS was 185 +/- 8
cm vs. 181 +/- 7 cm in controls. Hypergonadotropic hypogonadism develops during
early puberty in adolescents with Klinefelter's syndrome and remains compensated
in over 60% during ages 15-25, with sufficient testosterone secretion for
spontaneous accomplishment of pubertal development. Spermatozoa in semen are rare
and associated with T levels >7 nmol/L. Parameters reflecting androgen deficiency
in target tissues may help to optimise timing of testosterone substitution, which
should preferably not be initiated before fertility status has been clarified.
PMID- 27611180
TI - Rectal tube drainage reduces major anastomotic leakage after minimally invasive
rectal cancer surgery.
AB - AIM: Anastomotic leakage is the most serious complication following low anterior
resection for rectal cancer and is a major cause of postoperative morbidity and
mortality. The object of the present study was to investigate whether rectal tube
drainage can reduce anastomotic leakage after minimally invasive rectal cancer
surgery. METHOD: Three hundred and seventy-four patients who underwent
laparoscopic or robotic LAR for tumours located <= 15 cm above the anal verge
between 1 April 2012 and 31 October 2014 were assessed retrospectively. Of these,
107 with intermediate risk of anastomotic leakage received transanal rectal tube
drainage. The rectal tube group was matched by propensity score analysis with
patients not having rectal tube drainage, giving 204 patients in the study.
Covariates for propensity score analysis included age, sex, body mass index,
tumour height from the anal verge and preoperative chemoradiation. RESULTS:
Patient demographics, tumour location, preoperative chemoradiation and operative
results were similar between the two groups. The overall leakage rate was 10.8%
(22/204), with no significant difference between the rectal tube group (9.8%) and
the nonrectal tube group (11.8%, P = 0.652). Of the patients with anastomotic
leakage, major leakage requiring reoperation developed in 11.8% of those without
and 3.9% of those with a rectal tube. On multivariate analysis, age over 65 years
and nonuse of a rectal tube were found to be independent risk factors for major
anastomotic leakage. CONCLUSION: Rectal tube placement may be a safe and
effective method of reducing the rate of major anastomotic leakage, alleviating
the clinical course of leakage following minimally invasive rectal cancer
surgery.
PMID- 27611181
TI - Nonmotor symptoms in Parkinson's disease: are we still waiting for the honeymoon?
PMID- 27611182
TI - When do myopia genes have their effect? Comparison of genetic risks between
children and adults.
AB - Previous studies have identified many genetic loci for refractive error and
myopia. We aimed to investigate the effect of these loci on ocular biometry as a
function of age in children, adolescents, and adults. The study population
consisted of three age groups identified from the international CREAM consortium:
5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25
years. All participants had undergone standard ophthalmic examination including
measurements of axial length (AL) and corneal radius (CR). We examined the lead
SNP at all 39 currently known genetic loci for refractive error identified from
genome-wide association studies (GWAS), as well as a combined genetic risk score
(GRS). The beta coefficient for association between SNP genotype or GRS versus
AL/CR was compared across the three age groups, adjusting for age, sex, and
principal components. Analyses were Bonferroni-corrected. In the age group <10
years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age
group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and
in adults 20 loci were associated. Association with GRS increased with age; beta
= 0.0016 per risk allele (P = 2 * 10-8 ) in <10 years, 0.0033 (P = 5 * 10-15 ) in
10- to 25-year-olds, and 0.0048 (P = 1 * 10-72 ) in adults. Genes with strongest
effects (LAMA2, GJD2) had an early effect that increased with age. Our results
provide insights on the age span during which myopia genes exert their effect.
These insights form the basis for understanding the mechanisms underlying high
and pathological myopia.
PMID- 27611183
TI - Mutations targeting the plug-domain of the Shewanella oneidensis proton-driven
stator allow swimming at increased viscosity and under anaerobic conditions.
AB - Shewanella oneidensis MR-1 possesses two different stator units to drive
flagellar rotation, the Na+ -dependent PomAB stator and the H+ -driven MotAB
stator, the latter possibly acquired by lateral gene transfer. Although either
stator can independently drive swimming through liquid, MotAB-driven motors
cannot support efficient motility in structured environments or swimming under
anaerobic conditions. Using DeltapomAB cells we isolated spontaneous mutants able
to move through soft agar. We show that a mutation that alters the structure of
the plug domain in MotB affects motor functions and allows cells to swim through
media of increased viscosity and under anaerobic conditions. The number and
exchange rates of the mutant stator around the rotor were not significantly
different from wild-type stators, suggesting that the number of stators engaged
is not the cause of increased swimming efficiency. The swimming speeds of
planktonic mutant MotAB-driven cells was reduced, and overexpression of some of
these stators caused reduced growth rates, implying that mutant stators not
engaged with the rotor allow some proton leakage. The results suggest that the
mutations in the MotB plug domain alter the proton interactions with the stator
ion channel in a way that both increases torque output and allows swimming at
decreased pmf values.
PMID- 27611184
TI - Early Regional Inflammation: The Seeds of Lung Injury.
PMID- 27611186
TI - Aerobic Oxidation of Olefins and Lignin Model Compounds Using Photogenerated
Phthalimide-N-oxyl Radical.
AB - A metal-free protocol to generate phthalimide-N-oxyl (PINO) radicals from N
hydroxyphthalimide (NHPI) via a photoinduced proton-coupled electron transfer
process is reported. Using donor-substituted aromatic ketones, such as 4,4'
bis(diphenylamino)benzophenone (DPA-BP), PINO radicals are efficiently produced
and subsequently utilized to functionalize olefins to afford a new class of alkyl
hydroperoxides. The DPA-BP/NHPI/O2 photocatalytic system exhibits high efficiency
toward the aerobic oxidation of beta-O-4 lignin models.
PMID- 27611185
TI - Lung Metabolic Activation as an Early Biomarker of Acute Respiratory Distress
Syndrome and Local Gene Expression Heterogeneity.
AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is an inflammatory
condition comprising diffuse lung edema and alveolar damage. ARDS frequently
results from regional injury mechanisms. However, it is unknown whether
detectable inflammation precedes lung edema and opacification and whether
topographically differential gene expression consistent with heterogeneous injury
occurs in early ARDS. The authors aimed to determine the temporal relationship
between pulmonary metabolic activation and density in a large animal model of
early ARDS and to assess gene expression in differentially activated regions.
METHODS: The authors produced ARDS in sheep with intravenous lipopolysaccharide
(10 ng ? kg ? h) and mechanical ventilation for 20 h. Using positron emission
tomography, the authors assessed regional cellular metabolic activation with 2
deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with NN-saline, and
aeration using transmission scans. Species-specific microarray technology was
used to assess regional gene expression. RESULTS: Metabolic activation preceded
detectable increases in lung density (as required for clinical diagnosis) and
correlated with subsequent histologic injury, suggesting its predictive value for
severity of disease progression. Local time courses of metabolic activation
varied, with highly perfused and less aerated dependent lung regions activated
earlier than nondependent regions. These regions of distinct metabolic
trajectories demonstrated differential gene expression for known and potential
novel candidates for ARDS pathogenesis. CONCLUSIONS: Heterogeneous lung metabolic
activation precedes increases in lung density in the development of ARDS due to
endotoxemia and mechanical ventilation. Local differential gene expression occurs
in these early stages and reveals molecular pathways relevant to ARDS biology and
of potential use as treatment targets.
PMID- 27611187
TI - Evaluation of field resistance to Striga hermonthica (Del.) Benth. in Sorghum
bicolor (L.) Moench. The relationship with strigolactones.
AB - BACKGROUND: Significant losses in sorghum biomass and grain yield occur in sub
Saharan Africa owing to infection by the root-parasitic weed Striga hermonthica
(Del.) Benth. One strategy to avoid these losses is to adopt resistant crop
varieties. For further delineation of the role of germination stimulants in
resistance, we conducted a field experiment employing six sorghum genotypes, in
eastern Sudan, and in parallel analysed the strigolactone levels in the root
exudates of these genotypes under controlled conditions in Wageningen. RESULTS:
The root exudates of these genotypes displayed large differences in strigolactone
composition and Striga-germination-inducing activity. Korokollow, Fakimustahi and
Wadfahel exuded the highest amounts of 5-deoxystrigol. Fakimustahi was by far the
highest sorgomol producer, and Wadbaco and SRN39 produced the highest amount of
orobanchol. The concentration of 5-deoxystrigol in the root exudate showed a
significant positive correlation with in vitro Striga germination and was
positively associated with Striga infection in the field experiments, whereas
orobanchol was negatively associated with Striga infection in the field
experiments. CONCLUSION: For the first time a close association is reported
between strigolactone levels analysed under laboratory conditions and Striga
infection in the field in sorghum genotypes. These genotypes may be used for
further study of this resistance mechanism and for the introgression of the low
germination trait in other sorghum varieties to breed for a strigolactone
composition with low stimulant activity. The use of such improved varieties in
combination with other Striga management tools could possibly alleviate the
current Striga problem on the African continent. (c) 2016 Society of Chemical
Industry.
PMID- 27611188
TI - Joint Lung CT Image Segmentation: A Hierarchical Bayesian Approach.
AB - Accurate lung CT image segmentation is of great clinical value, especially when
it comes to delineate pathological regions including lung tumor. In this paper,
we present a novel framework that jointly segments multiple lung computed
tomography (CT) images via hierarchical Dirichlet process (HDP). In specifics,
based on the assumption that lung CT images from different patients share similar
image structure (organ sets and relative positioning), we derive a mathematical
model to segment them simultaneously so that shared information across patients
could be utilized to regularize each individual segmentation. Moreover, compared
to many conventional models, the algorithm requires little manual involvement due
to the nonparametric nature of Dirichlet process (DP). We validated proposed
model upon clinical data consisting of healthy and abnormal (lung cancer)
patients. We demonstrate that, because of the joint segmentation fashion, more
accurate and consistent segmentations could be obtained.
PMID- 27611190
TI - Correction: Market Structure, Financial Dependence and Industrial Growth:
Evidence from the Banking Industry in Emerging Asian Economies.
AB - [This corrects the article DOI: 10.1371/journal.pone.0160452.].
PMID- 27611189
TI - Targeting Attenuated Interferon-alpha to Myeloma Cells with a CD38 Antibody
Induces Potent Tumor Regression with Reduced Off-Target Activity.
AB - Interferon-alpha (IFNalpha) has been prescribed to effectively treat multiple
myeloma (MM) and other malignancies for decades. Its use has waned in recent
years, however, due to significant toxicity and a narrow therapeutic index (TI).
We sought to improve IFNalpha's TI by, first, attaching it to an anti-CD38
antibody, thereby directly targeting it to MM cells, and, second, by introducing
an attenuating mutation into the IFNalpha portion of the fusion protein rendering
it relatively inactive on normal, CD38 negative cells. This anti-CD38
IFNalpha(attenuated) immunocytokine, or CD38-AttenukineTM, exhibits 10,000-fold
increased specificity for CD38 positive cells in vitro compared to native
IFNalpha and, significantly, is ~6,000-fold less toxic to normal bone marrow
cells in vitro than native IFNalpha. Moreover, the attenuating mutation
significantly decreases IFNalpha biomarker activity in cynomolgus macaques
indicating that this approach may yield a better safety profile in humans than
native IFNalpha or a non-attenuated IFNalpha immunocytokine. In human xenograft
MM tumor models, anti-CD38-IFNalpha(attenuated) exerts potent anti-tumor activity
in mice, inducing complete tumor regression in most cases. Furthermore, anti-CD38
IFNalpha(attenuated) is more efficacious than standard MM treatments
(lenalidomide, bortezomib, dexamethasone) and exhibits strong synergy with
lenalidomide and with bortezomib in xenograft models. Our findings suggest that
tumor-targeted attenuated cytokines such as IFNalpha can promote robust tumor
killing while minimizing systemic toxicity.
PMID- 27611192
TI - Effects of a Plant Sterol or Stanol Enriched Mixed Meal on Postprandial Lipid
Metabolism in Healthy Subjects.
AB - BACKGROUND: Evidence is increasing that plant sterols and stanols not only lower
fasting serum low-density lipoprotein concentrations, but also those of
triglycerides (TG). Insight into effects of these components on postprandial TG
metabolism, an emerging risk factor for cardiovascular disease, is missing.
OBJECTIVE: Our objective was to examine the 8-hour postprandial response after
consuming plant sterol or stanol enriched margarine as part of a mixed meal.
METHODS: This postprandial study was part of a randomized crossover study in
which 42 subjects consumed plant sterol enriched (3 g/d plant sterols), plant
stanol enriched (3 g/d plant stanols), and control margarines for 4 weeks. After
each period, subjects consumed a shake enriched with 3g plant sterols (sterol
period), 3g plant stanols (stanol period) or no addition (control period).
Subjects received a second shake with no addition after 4 hours. RESULTS: TG and
apoB48 incremental areas under the curves (iAUC) of the total (0-8h) and 1st meal
response (0-4h) were comparable between the meals and in all age categories (I:18
35y, II:36-52y, III:53-69y). In subjects aged 53-69y, TG iAUC after the 2nd meal
(4-8h) was higher in the stanol period as compared with the sterol (63.1+/-53.0
mmol/L/min; P < 0.01) and the control period (43.2+/-52.4 mmol/L/min; P < 0.05).
ApoB48 iAUC after the 2nd meal was higher after the stanol than after the sterol
period (67.1+/-77.0 mg/L/min; P < 0.05) and tended to be higher than after the
control period (43.1+/-64.5 mg/L/min; P = 0.08) in subjects aged 53-69y. These
increased postprandial responses may be due to reduced lipoprotein lipase
activity, since postprandial apoCIII/II ratios were increased after stanol
consumption compared with the control meal. CONCLUSION: Postprandial TG and
apoB48 responses are age-dependently increased after plant stanol consumption,
which might be related to a changed clearance of triglyceride-rich lipoproteins.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01559428.
PMID- 27611191
TI - Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the
Frog Visual System after Optic Nerve Injury.
AB - After lesions to the mammalian optic nerve, the great majority of retinal
ganglion cells (RGCs) die before their axons have even had a chance to
regenerate. Frog RGCs, on the other hand, suffer only an approximately 50% cell
loss, and we have previously investigated the mechanisms by which the application
of growth factors can increase their survival rate. Retinoic acid (RA) is a
vitamin A-derived lipophilic molecule that plays major roles during development
of the nervous system. The RA signaling pathway is also present in parts of the
adult nervous system, and components of it are upregulated after injury in
peripheral nerves but not in the CNS. Here we investigate whether RA signaling
affects long-term RGC survival at 6 weeks after axotomy. Intraocular injection of
all-trans retinoic acid (ATRA), the retinoic acid receptor (RAR) type-alpha
agonist AM80, the RARbeta agonist CD2314, or the RARgamma agonist CD1530,
returned axotomized RGC numbers to almost normal levels. On the other hand,
inhibition of RA synthesis with disulfiram, or of RAR receptors with the pan-RAR
antagonist Ro-41-5253, or the RARbeta antagonist LE135E, greatly reduced the
survival of the axotomized neurons. Axotomy elicited a strong activation of the
MAPK, STAT3 and AKT pathways; this activation was prevented by disulfiram or by
RAR antagonists. Finally, addition of exogenous ATRA stimulated the activation of
the first two of these pathways. Future experiments will investigate whether
these strong survival-promoting effects of RA are mediated via the upregulation
of neurotrophins.
PMID- 27611193
TI - One Odontogenic Cell-Population Contributes to the Development of the Mouse
Incisors and of the Oral Vestibule.
AB - The area of the oral vestibule is often a place where pathologies appear (e.g.,
peripheral odontomas). The origin of these pathologies is not fully understood.
In the present study, we traced a cell population expressing Sonic hedgehog (Shh)
from the beginning of tooth development using Cre-LoxP system in the lower jaw of
wild-type (WT) mice. We focused on Shh expression in the area of the early
appearing rudimentary incisor germs located anteriorly to the prospective
incisors. The localization of the labelled cells in the incisor germs and also in
the inner epithelial layer of the vestibular anlage showed that the first very
early developmental events in the lower incisor area are common to the vestibulum
oris and the prospective incisor primordia in mice. Scanning electron microscopic
analysis of human historical tooth-like structures found in the vestibular area
of jaws confirmed their relation to teeth and thus the capability of the
vestibular tissue to form teeth. The location of labelled cells descendant of the
early appearing Shh expression domain related to the rudimentary incisor anlage
not only in the rudimentary and functional incisor germs but also in the
externally located anlage of the oral vestibule documented the odontogenic
potential of the vestibular epithelium. This potential can be awakened under
pathological conditions and become a source of pathologies in the vestibular
area.
PMID- 27611194
TI - The Use of Poly-L-Lysine as a Capture Agent to Enhance the Detection of
Antinuclear Antibodies by ELISA.
AB - Antibodies to nuclear antigens (antinuclear antibodies or ANAs) are the
serological hallmark of systemic lupus erythematosus (SLE). These antibodies bind
diverse nuclear antigens that include DNA, histones and non-histone proteins as
well as complexes of proteins with DNA and RNA. Because of the frequency of ANA
expression in SLE, testing is an important component of clinical evaluation as
well as determination of eligibility for clinical trials or utilization of
certain therapies. Immunofluorescence assays have been commonly used for this
purpose although this approach can be limited by issues of throughput,
variability and difficulty in determining positivity. ELISA and multiplex assays
are also useful approaches although these assays may give an incomplete picture
of antibodies present. To develop a sensitive and quantitative ANA assay, we have
explored an ELISA platform in which plates are pre-coated with a positively
charged nucleic acid binding polymer (NABP) to increase adherence of antigens
containing DNA or RNA. As a source of antigens, we have used supernatants of
Jurkat cells undergoing apoptosis in vitro. As results presented show, a poly-L
lysine (PLL) pre-coat significantly enhances detection of antibodies to DNA as
well as antigens such as histones, SSA, SSB and RNP. Comparison of the ELISA
assay with the PLL pre-coat with a multiplex assay using the BioPlex(r) 2200
system indicated good agreement in results for a panel of lupus sera. Together,
these studies indicate that a pre-coat with a positively charged polymer can
increase the sensitivity of an ANA ELISA using as antigens molecules released
from dead and dying cells. This assay platform may facilitate ANA testing by
providing an ensemble of antigens more similar in composition and structure with
antigens present in vivo, with a NABP promoting adherence via charge-charge
interactions.
PMID- 27611195
TI - Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in
Myanmar.
AB - This study aims to describe betel quid chewing practice and compare oral
potentially malignant disorders between chewers and non-chewers of betel quid
among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross
sectional design conducted with a representative sample of 542 adults aged 18
years and above in the township. The trained interviewers collected data using a
pretested structured questionnaire. On-site oral examination was done for
suspected oral lesions. The mean age of the respondents was 45 years and 59% were
women. Fifty-two percent of the respondents were currently in the habit of
chewing betel quids (72% of men and 39% of women). Among 284 current betel quid
chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current
betel quid chewers, 24 (8.5%) were found to have oral potentially malignant
disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have
oral potentially malignant disorders. This highlights the growing importance of
smokeless tobacco use as public health problem.
PMID- 27611196
TI - Current and future risks of asbestos exposure in the Australian community.
AB - BACKGROUND: Australia mined asbestos for more than 100 years and manufactured and
imported asbestos products. There is a legacy of in situ asbestos throughout the
built environment. METHODS: The aim of this study was to identify the possible
sources of current and future asbestos exposure from the built environment.
Telephone interviews with environmental health officers, asbestos removalists,
and asbestos assessors in Australia sought information about common asbestos
scenarios encountered. RESULTS: There is a considerable amount of asbestos
remaining in situ in the Australian built environment. Potential current and
future sources of asbestos exposure to the public are from asbestos-containing
roofs and fences, unsafe asbestos removal practices, do-it-yourself home
renovations and illegal dumping. CONCLUSION: This research has highlighted a need
for consistent approaches in the regulation and enforcement of safe practices for
the management and removal of asbestos to ensure that in situ asbestos in the
built environment is managed appropriately.
PMID- 27611199
TI - Abundant Topological Outliers in Social Media Data and Their Effect on Spatial
Analysis.
AB - Twitter and related social media feeds have become valuable data sources to many
fields of research. Numerous researchers have thereby used social media posts for
spatial analysis, since many of them contain explicit geographic locations.
However, despite its widespread use within applied research, a thorough
understanding of the underlying spatial characteristics of these data is still
lacking. In this paper, we investigate how topological outliers influence the
outcomes of spatial analyses of social media data. These outliers appear when
different users contribute heterogeneous information about different phenomena
simultaneously from similar locations. As a consequence, various messages
representing different spatial phenomena are captured closely to each other, and
are at risk to be falsely related in a spatial analysis. Our results reveal
indications for corresponding spurious effects when analyzing Twitter data.
Further, we show how the outliers distort the range of outcomes of spatial
analysis methods. This has significant influence on the power of spatial
inferential techniques, and, more generally, on the validity and interpretability
of spatial analysis results. We further investigate how the issues caused by
topological outliers are composed in detail. We unveil that multiple disturbing
effects are acting simultaneously and that these are related to the geographic
scales of the involved overlapping patterns. Our results show that at some scale
configurations, the disturbances added through overlap are more severe than at
others. Further, their behavior turns into a volatile and almost chaotic
fluctuation when the scales of the involved patterns become too different.
Overall, our results highlight the critical importance of thoroughly considering
the specific characteristics of social media data when analyzing them spatially.
PMID- 27611197
TI - Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive
Like Behavior When Combined with Postweaning Social Isolation in Rats.
AB - Early-life stress is associated with depression and metabolic abnormalities that
increase the risk of cardiovascular disease and diabetes. Such associations could
be due to increased glucocorticoid levels. Periodic maternal separation in the
neonate and rearing in social isolation are potent stressors that increase
hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes
feed intake and body weight gain in rats subjected to periodic maternal
separation; however, its effects on metabolic risks have not been described. In
the present study, we evaluated whether periodic maternal separation, social
isolation rearing, and a combination of these two stressors (periodic maternal
separation + social isolation rearing) impair glucose homeostasis and its
relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior.
Periodic maternal separation increased basal corticosterone levels, induced a
passive coping strategy in the forced swimming test, and was associated with a
mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia.
Rearing in social isolation increased stress reactivity in comparison to both
controls and in combination with periodic maternal separation, without affecting
the coping strategy associated with the forced swimming test. However, social
isolation also increased body weight gain, fasting glucose (120%), and insulin
levels in rats subjected to periodic maternal separation. Correlation analyses
showed that stress-induced effects on coping strategy on the forced swimming test
(but not on metabolic risk markers) are associated with basal corticosterone
levels. These findings suggest that maternal separation and postweaning social
isolation affect stress and metabolic vulnerability differentially and that early
life stress-related effects on metabolism are not directly dependent on
glucocorticoid levels. In conclusion, our study supports the cumulative stress
hypothesis, which suggests that metabolic risk markers arise when vulnerable
individuals are exposed to social challenges later in life.
PMID- 27611200
TI - Speech changes induced by deep brain stimulation of the subthalamic nucleus in
Parkinson disease: involvement of the dentatorubrothalamic tract.
AB - OBJECTIVE Patients with Parkinson disease (PD) who undergo subthalamic nucleus
(STN) deep brain stimulation (DBS) often develop a deterioration in speech
performance, but there is no clear consensus on the specific effects seen or the
mechanism involved and little description of the impact of DBS on conversational
speech. Furthermore, there has been no fiber tract connectivity analysis to
identify the structures potentially modulated by DBS to cause such deficits. The
main objective of this study was to quantify spontaneous speech performance and
identify potential involvement of the dentatorubrothalamic tract (DRTt) in
patients who underwent STN DBS, because this tract has been implicated in speech
deterioration. METHODS Spontaneous speech samples were obtained with STN DBS in
both on and off modes in 35 patients with PD and assessed across multiple
domains. Diffusion tensor imaging tractography seeded from the therapeutic DBS
contacts was performed to identify the fiber tracts involved and, specifically,
the DRTt. The position of active electrode contacts was assessed relative to that
of the STN. RESULTS Fifteen patients with akinetic-rigid (AR) PD and 20 with
tremor-dominant (TD) PD subtypes were identified. In the AR-PD subgroup of
patients, in whom there was DRTt involvement, 71% demonstrated much better
overall speech and largely improved or unchanged fluency in the DBS-off
condition. In patients with TD PD with DRTt involvement, 50% demonstrated better
overall speech in the off condition, and equivocal results regarding improved or
worsened fluency were found. When there was minimal DRTt involvement, 75% of
patients with AR PD had better overall speech in the DBS-on condition and better
or minimal fluency changes. Similarly, 83% of patients with TD PD with minimal
DRTt involvement had better or minimal overall speech and fluency changes in the
on condition. More medially placed left electrode contacts were associated with
more DRTt involvement in 77% of patients (10 of 13). CONCLUSIONS To the authors'
knowledge, this is the first study to have investigated a specific fiber tract
involved in STN DBS in different subtypes of PD relative to its impact on
spontaneous speech. At optimal therapeutic programming of STN DBS, overall
spontaneous speech and fluency were affected more negatively in patients with AR
PD than in those with TD PD when there was DRTt involvement. After fiber tract
analysis and modeling, it was found that medially positioned left electrode
contacts more often involved fibers of the DRTt. If possible, avoidance of the
DRTt by using active electrode contacts that are positioned less medially,
specifically in patients with AR PD, might result in less speech deterioration.
PMID- 27611198
TI - Impact of Season, Demographic and Environmental Factors on Salmonella Occurrence
in Raccoons (Procyon lotor) from Swine Farms and Conservation Areas in Southern
Ontario.
AB - Salmonella has been detected in the feces of many wildlife species, including
raccoons (Procyon lotor), but little is known about the epidemiology of
Salmonella in wildlife living in different habitat types. Our objective was to
investigate demographic, temporal, and climatic factors associated with the
carriage of Salmonella in raccoons and their environment on swine farms and
conservation areas. Using a repeated cross-sectional study design, we collected
fecal samples from raccoons and environmental samples (soil, manure pits,
dumpsters) on 5 swine farms and 5 conservation areas in Ontario, Canada once
every five weeks from May to November, 2011-2013. Salmonella was detected in 26%
(279/1093; 95% CI 22.9-28.2) of raccoon fecal samples, 6% (88/1609; 95% CI 4.5
6.8) of soil samples, 30% (21/69; 95% CI 20.0-42.7) of manure pit samples, and
23% (7/31; 95% CI 9.6-41.0) of dumpster samples. Of samples testing positive for
Salmonella, antimicrobial resistance was detected in 5% (14/279; 95% CI 2.8-8.3)
of raccoon fecal, 8% (7/89; 95% CI 3.2-15.5) of soil, 10% (2/21; 95% CI 1.2-30.4)
of manure pit, and 0/7 dumpster samples. Using multi-level multivariable logistic
regression analyses, we found location type (swine farm or conservation area) was
not a significant explanatory variable for Salmonella occurrence in raccoon feces
or soil (p > 0.05). However, detection of Salmonella in raccoon feces was
associated with rainfall, season, and sex with various interaction effects among
these variables. We detected a variety of Salmonella serovars that infect humans
and livestock in the feces of raccoons indicating that raccoons living near
humans, regardless of location type, may play a role in the epidemiology of
salmonellosis in livestock and humans in southwestern Ontario.
PMID- 27611201
TI - Adjuvant radiotherapy for atypical meningiomas.
AB - OBJECTIVE The aim of this paper was to evaluate outcomes in patients with
atypical meningiomas (AMs) treated with surgery alone compared with surgery and
radiotherapy at initial diagnosis, or at the time of first recurrence. METHODS
Patients with pathologically confirmed AMs treated at the University of Utah from
1991 to 2014 were retrospectively reviewed. Local control (LC), overall survival
(OS), Karnofsky Performance Status (KPS), and toxicity were assessed. Outcomes
for patients receiving adjuvant radiotherapy were compared with those for
patients treated with surgery alone. Kaplan-Meier and the log-rank test for
significance were used for LC and OS analyses. RESULTS Fifty-nine patients with
63 tumors were reviewed. Fifty-two patients were alive at the time of analysis
with a median follow-up of 42 months. LC for all tumors was 57% with a median
time to local failure (TTLF) of 48 months. The median TTLF following surgery and
radiotherapy was 180 months, compared with 46 months following surgery alone (p =
0.02). Excluding Simpson Grade IV (subtotal) resections, there remained an LC
benefit with the addition of radiotherapy for Simpson Grade I, II, and III
resected tumors (median TTLF 180 months after surgery and radiotherapy compared
with 46 months with surgery alone [p = 0.002]). Patients treated at first
recurrence following any initial therapy (either surgery alone or surgery and
adjuvant radiotherapy) had a median TTLF of 26 months compared with 48 months for
tumors treated at first diagnosis (p = 0.007). There were 2 Grade 3 toxicities
and 1 Grade 4 toxicity associated with radiotherapy. CONCLUSIONS Adjuvant
radiotherapy improves LC for AMs. The addition of adjuvant radiotherapy following
even a Simpson Grade I, II, or III resection was found to confer an LC benefit.
Recurrent disease is difficult to control, underscoring the importance of
aggressive initial treatment.
PMID- 27611202
TI - Letter to the Editor: Resection of olfactory groove meningiomas.
PMID- 27611203
TI - Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation
detected by whole exome sequencing.
AB - OBJECTIVE Brain arteriovenous malformations (AVMs) can occur in patients with
hereditary hemorrhagic telangiectasia (HHT). However, brain AVM without HHT has
also been reported. Using whole exome sequencing, the authors performed
comprehensive genomic characterization of a 6-person Turkish family with 3 cases
of brain AVM without HHT. METHODS Three siblings with brain AVM, one of whom also
had spinal AVM, were evaluated. The parents and the fourth sibling had no AVM on
cranial MRI. The authors performed a whole exome capture and Illumina sequencing
on blood samples from 2 siblings with AVM. RESULTS An ACVRL1 heterozygous
mutation (p.Lys332Glu) was identified in 2 patients via whole exome sequencing.
Variant segregation was confirmed using direct Sanger sequencing. CONCLUSIONS
Study results suggested that whole exome sequencing analysis is particularly
useful in cases of locus heterogeneity and uncertain diagnostic classification
schemes in patients with hereditary brain AVM.
PMID- 27611204
TI - Impact of insurance precertification on neurosurgery practice and health care
delivery.
AB - OBJECTIVE Insurance preauthorization is used as a third-party tool to reduce
health care costs. Given the expansion of managed care, the impact of the
insurance preauthorization process in delaying health care delivery warrants
investigation through a diversified neurosurgery practice. METHODS Data for 1985
patients were prospectively gathered over a 12-month period from July 1, 2014,
until June 30, 2015. Information regarding attending, procedure, procedure type,
insurance type, need for insurance approval, number of days for authorization, or
insurance denial was obtained. Delay in authorization was defined as any wait
period greater than 7 days. Some of the parameters were added retrospectively to
enhance this study; hence, the total number of subjects may vary for different
variables. RESULTS The most common procedure was back surgery with
instrumentation (28%). Most of the patients had commercial insurance (57%) while
Medicaid was the least common (1%). Across all neurosurgery procedures, insurance
authorization, on average, was delayed 9 days with commercial insurance, 10.7
days with Tricare insurance, 8.5 days with Medicare insurance, 11.5 days with
Medicaid, and 14.4 days with workers' compensation. Two percent of all patients
were denied insurance preauthorization without any statistical trend or
association. Of the 1985 patients, 1045 (52.6%) patients had instrumentation
procedures. Independent of insurance type, instrumentation procedures were more
likely to have delays in authorization (p = 0.001). Independent of procedure
type, patients with Tricare (military) insurance were more likely to have a delay
in approval for surgery (p = 0.02). Predictably, Medicare insurance was
protective against a delay in surgery (p = 0.001). CONCLUSIONS Choice of
insurance provider and instrumentation procedures were independent risk factors
for a delay in insurance preauthorization. Neurosurgeons, not just policy makers,
must take ownership to analyze, investigate, and interpret these data to deliver
the best and most efficient care to our patients.
PMID- 27611205
TI - Letter to the Editor: Evoked potentials and Chiari malformation Type 1.
PMID- 27611207
TI - Letter to the Editor: Are arachnoid cysts and Chiari malformation Type I more
common in those with postconcussion syndrome?
PMID- 27611206
TI - Intraoperative image updating for brain shift following dural opening.
AB - OBJECTIVE Preoperative magnetic resonance images (pMR) are typically coregistered
to provide intraoperative navigation, the accuracy of which can be significantly
compromised by brain deformation. In this study, the authors generated updated MR
images (uMR) in the operating room (OR) to compensate for brain shift due to
dural opening, and evaluated the accuracy and computational efficiency of the
process. METHODS In 20 open cranial neurosurgical cases, a pair of intraoperative
stereovision (iSV) images was acquired after dural opening to reconstruct a 3D
profile of the exposed cortical surface. The iSV surface was registered with pMR
to detect cortical displacements that were assimilated by a biomechanical model
to estimate whole-brain nonrigid deformation and produce uMR in the OR. The uMR
views were displayed on a commercial navigation system and compared side by side
with the corresponding coregistered pMR. A tracked stylus was used to acquire
coordinate locations of features on the cortical surface that served as
independent positions for calculating target registration errors (TREs) for the
coregistered uMR and pMR image volumes. RESULTS The uMR views were visually more
accurate and well aligned with the iSV surface in terms of both geometry and
texture compared with pMR where misalignment was evident. The average misfit
between model estimates and measured displacements was 1.80 +/- 0.35 mm, compared
with the average initial misfit of 7.10 +/- 2.78 mm between iSV and pMR, and the
average TRE was 1.60 +/- 0.43 mm across the 20 patients in the uMR image volume,
compared with 7.31 +/- 2.82 mm on average in the pMR cases. The iSV also proved
to be accurate with an average error of 1.20 +/- 0.37 mm. The overall
computational time required to generate the uMR views was 7-8 minutes.
CONCLUSIONS This study compensated for brain deformation caused by intraoperative
dural opening using computational model-based assimilation of iSV cortical
surface displacements. The uMR proved to be more accurate in terms of model-data
misfit and TRE in the 20 patient cases evaluated relative to pMR. The
computational time was acceptable (7-8 minutes) and the process caused minimal
interruption of surgical workflow.
PMID- 27611208
TI - Are Hispanic patients with subarachnoid hemorrhage treated differently in border
states than in nonborder states?
AB - OBJECTIVE Recent studies have found an underutilization of in-hospital procedures
in treatments of Hispanic patients admitted with coronary artery disease in
states along the US-Mexico border ("border states"). The purpose of this study
was to determine any treatment disparities between patients treated for
subarachnoid hemorrhage (SAH) in border and nonborder states and whether this
disparity was associated with differential hospital charges. METHODS Using the
National (Nationwide) Inpatient Sample, the authors retrieved data of Hispanic
and non-Hispanic patients who were admitted in 2011 for SAH in a border state
(California, Arizona, New Mexico, and Texas) or nonborder state (the remaining 46
US states). The authors determined the rates of use of endovascular coiling and
surgical clipping treatments, hospital charges, and outcomes according to the
patients' demographics and treatment in border or nonborder states. RESULTS In
total, 18,368 patients were admitted with SAH in the selected time period,
including 2310 Hispanic patients (12.6%). Of these patients, 1525 were admitted
in a border state and 785 in a nonborder state. In border states, rates of
surgical treatment significantly differed between patients of Hispanic (21.9%)
and non-Hispanic (14.0%) origin (p = 0.02). In particular, Hispanic patients were
more likely to undergo surgical clipping than were non-Hispanic patients. In the
nonborder states, the rates of surgical treatment were similar for Hispanic and
non-Hispanic patients (14.0% vs 15.6%, p = 0.6). Hispanic patients with SAH were
billed significantly higher in-hospital charges in border states than in
nonborder states ($219,260 and $192,418 [US dollars], respectively, p < 0.001).
CONCLUSIONS Use of surgical treatments for Hispanic patients with SAH residing in
border states has a unique pattern, which significantly increases in-hospital
charges in this patient population.
PMID- 27611209
TI - Development of an Activated Carbon-Based Electrode for the Capture and Rapid
Electrolytic Reductive Debromination of Methyl Bromide from Postharvest
Fumigations.
AB - Due to concerns surrounding its ozone depletion potential, there is a need for
technologies to capture and destroy methyl bromide (CH3Br) emissions from
postharvest fumigations applied to control agricultural pests. Previously, we
described a system in which CH3Br fumes vented from fumigation chambers could be
captured by granular activated carbon (GAC). The GAC was converted to a cathode
by submergence in a high ionic strength solution and connection to the electrical
grid, resulting in reductive debromination of the sorbed CH3Br. The GAC bed was
drained and dried for reuse to capture and destroy CH3Br fumes from the next
fumigation. However, the loose GAC particles and slow kinetics of this primitive
electrode necessitated improvements. Here, we report the development of a cathode
containing a thin layer of small GAC particles coating carbon cloth as a current
distributor. Combining the high sorption potential of GAC for CH3Br with the
conductivity of the carbon cloth current distributor, the cathode significantly
lowered the total cell resistance and achieved 96% reductive debromination of
CH3Br sorbed at 30% by weight to the GAC within 15 h at -1 V applied potential vs
standard hydrogen electrode, a time scale and efficiency suitable for postharvest
fumigations. The cathode exhibited stable performance over 50 CH3Br capture and
destruction cycles. Initial cost estimates indicate that this technique could
treat CH3Br fumes at ~$5/kg, roughly one-third of the cost of current
alternatives.
PMID- 27611211
TI - Statement of Removal.
PMID- 27611210
TI - Transient Suppression of Dbx1 PreBotzinger Interneurons Disrupts Breathing in
Adult Mice.
AB - Interneurons derived from Dbx1-expressing precursors located in the brainstem
preBotzinger complex (preBotC) putatively form the core oscillator for
inspiratory breathing movements. We tested this Dbx1 core hypothesis by
expressing archaerhodopsin in Dbx1-derived interneurons and then transiently
hyperpolarizing these neurons while measuring respiratory rhythm in vitro or
breathing in vagus-intact adult mice. Transient illumination of the preBotC
interrupted inspiratory rhythm in both slice preparations and sedated mice. In
awake mice, light application reduced breathing frequency and prolonged the
inspiratory duration. Support for the Dbx1 core hypothesis previously came from
embryonic and perinatal mouse experiments, but these data suggest that Dbx1
derived preBotC interneurons are rhythmogenic in adult mice too. The neural
origins of breathing behavior can be attributed to a localized and genetically
well-defined interneuron population.
PMID- 27611212
TI - Neural mechanisms and personality correlates of the sunk cost effect.
AB - The sunk cost effect, an interesting and well-known maladaptive behavior, is
pervasive in real life, and thus has been studied in various disciplines,
including economics, psychology, organizational behavior, politics, and biology.
However, the neural mechanisms underlying the sunk cost effect have not been
clearly established, nor have their association with differences in individual
susceptibility to the effect. Using functional magnetic resonance imaging, we
investigated neural responses induced by sunk costs along with measures of core
human personality. We found that individuals who tend to adhere to social rules
and regulations (who are high in measured agreeableness and conscientiousness)
are more susceptible to the sunk cost effect. Furthermore, this behavioral
observation was strongly mediated by insula activity during sunk cost decision
making. Tight coupling between the insula and lateral prefrontal cortex was also
observed during decision-making under sunk costs. Our findings reveal how
individual differences can affect decision-making under sunk costs, thereby
contributing to a better understanding of the psychological and neural mechanisms
of the sunk cost effect.
PMID- 27611213
TI - APOBEC3G governs the generation of truncated AATF protein to ensure oncogenic
transformation.
AB - The oncogenic potential of Apolipoprotein B mRNA editing enzyme, catalytic
polypeptide-like 3G (APOBEC3G) was recently appreciated by the finding that
revealed its ability to downregulate Kruppel-like factor 4 (KLF4) gene
translation through its affinity for 3'UTR of KLF4 mRNA. Keeping in view the fact
that KLF4 is known to repress apoptosis antagonizing transcription factor (AATF)
gene expression, the present study employed stem cells as archetype model to
explore the effect of APOBEC3G over-expression upon AATF gene expression within
these cells as well as on the genes involved in oncogenic transformation. Such a
study revealed that APOBEC3G had the ability to bind AATF mRNA within its third
exon to facilitate the generation of truncated 23 kDa AATF translation product
which, in turn, had the inherent capacity to be the crucial mediator of APOBEC3G
induced oncogenic transformation within such cells.
PMID- 27611216
TI - Assessment of the cell biovolume of phytoplankton widespread in coastal and
inland water bodies.
AB - The biovolume of phytoplankton must be assessed accurately in order to identify
the ecological status of water bodies in line with the WFD requirements. Hence,
the current study has been carried out to verify and improve the precision of as
well as to facilitate and accelerate estimations of phytoplankton biovolume by
reviewing and rearranging the basic geometrical shapes of these organisms applied
in such evaluations. The latest standards comprise 17 geometric shapes and
equations suitable for estimations of cell/filament/colony biovolume and
additionally include taxa-specific 'geometric correction factors' to fit real
shapes and 'hidden dimension factors' to achieve data on hardly measureable
dimensions. This paper also discusses possible obstacles to making correct
biovolume assessments, especially when analyzing taxa of special concern, e.g.
Ceratium hirundinella, C. furcoides or Pediastrum duplex and Pseudopediastrum
boryanum. Our comparison of two approaches, the previous and the new one,
revealed that they yield statistically significantly different biovolume results
of these species. Some recommendations how to deal with the new and old methods
of biovolume estimations and how to reduce the possibility of errors with
overestimation and underestimation were also given. The more recent method can be
said to give more precise estimates of phytoplankton biovolume. Besides, it
facilitates more rapid phytoplankton analyses in most cases, which is very useful
when assessing the ecological status of lakes during routine monitoring programs.
PMID- 27611215
TI - Dual-Energy Contrast-Enhanced Spectral Mammography: Enhancement Analysis on BI
RADS 4 Non-Mass Microcalcifications in Screened Women.
AB - BACKGROUND: Mammography screening is a cost-efficient modality with high
sensitivity for detecting impalpable cancer with microcalcifications, and results
in reduced mortality rates. However, the probability of finding
microcalcifications without associated cancerous masses varies. We
retrospectively evaluated the diagnosis and cancer probability of the non-mass
screened microcalcifications by dual-energy contrast-enhanced spectral
mammography (DE-CESM). PATIENTS AND METHODS: With ethical approval from our
hospital, we enrolled the cases of DE-CESM for analysis under the following
inclusion criteria: (1) referrals due to screened BI-RADS 4 microcalcifications;
(2) having DE-CESM prior to stereotactic biopsy; (3) no associated mass found by
sonography and physical examination; and (4) pathology-based diagnosis using
stereotactic vacuum-assisted breast biopsy. We analyzed the added value of post
contrast enhancement on DE-CESM. RESULTS: A total of 94 biopsed lesions were
available for analysis in our 87 women, yielding 27 cancers [19 ductal carcinoma
in situ (DCIS), and 8 invasive ductal carcinoma (IDC)], 32 pre-malignant and 35
benign lesions. Of these 94 lesions, 33 showed associated enhancement in DE-CESM
while the other 61 did not. All 8 IDC (100%) and 16 of 19 DCIS (84.21%) showed
enhancement, but the other 3 DCIS (15.79%) did not. Overall sensitivity,
specificity, positive predictive value, negative predictive value and accuracy
were 88.89%, 86.56%, 72.72%, 95.08% and 87.24%, respectively. The performances of
DE-CESM on both amorphous and pleomorphic microcalcifications were satisfactory
(AUC 0.8 and 0.92, respectively). The pleomorphous microcalcifications with
enhancement showed higher positive predictive value (90.00% vs 46.15%, p = 0.013)
and higher cancer probability than the amorphous microcalcifications (46.3% VS
15.1%). The Odds Ratio was 4.85 (95% CI: 1.84-12.82). CONCLUSION: DE-CESM might
provide added value in assessing the non-mass screened breast microcalcification,
with enhancement favorable to the diagnosis of cancers or lack of enhancement
virtually diagnostic for non-malignant lesions or noninvasive subgroup cancers.
PMID- 27611214
TI - Efficient sensory cortical coding optimizes pursuit eye movements.
AB - In the natural world, the statistics of sensory stimuli fluctuate across a wide
range. In theory, the brain could maximize information recovery if sensory
neurons adaptively rescale their sensitivity to the current range of inputs. Such
adaptive coding has been observed in a variety of systems, but the premise that
adaptation optimizes behaviour has not been tested. Here we show that adaptation
in cortical sensory neurons maximizes information about visual motion in pursuit
eye movements guided by that cortical activity. We find that gain adaptation
drives a rapid (<100 ms) recovery of information after shifts in motion variance,
because the neurons and behaviour rescale their sensitivity to motion
fluctuations. Both neurons and pursuit rapidly adopt a response gain that
maximizes motion information and minimizes tracking errors. Thus, efficient
sensory coding is not simply an ideal standard but a description of real sensory
computation that manifests in improved behavioural performance.
PMID- 27611217
TI - Human Detection Using Random Color Similarity Feature and Random Ferns
Classifier.
AB - We explore a novel approach for human detection based on random color similarity
feature (RCS) and random ferns classifier which is also known as semi-naive
Bayesian classifier. In contrast to other existing features employed by human
detection, color-based features are rarely used in vision-based human detection
because of large intra-class variations. In this paper, we propose a novel color
based feature, RCS feature, which is yielded by simple color similarity
computation between image cells randomly picked in still images, and can
effectively characterize human appearances. In addition, a histogram of oriented
gradient based local binary feature (HOG-LBF) is also introduced to enrich the
human descriptor set. Furthermore, random ferns classifier is used in the
proposed approach because of its faster speed in training and testing than
traditional classifiers such as Support Vector Machine (SVM) classifier, without
a loss in performance. Finally, the proposed method is conducted in public
datasets and achieves competitive detection results.
PMID- 27611218
TI - Aquatic toxicity structure-activity relationships for the zwitterionic surfactant
alkyl dimethyl amine oxide to several aquatic species and a resulting species
sensitivity distribution.
AB - Amine oxide (AO) is a cationically charged surfactant at environmental pH and has
previously been assessed in the OECD (Organization for Economic Cooperation and
Development) High Production Volume (HPV) chemicals program. Typical of cationic
chemicals, AO is highly aquatically toxic. In this study we vastly improve the
knowledge of AO toxicity by developing acute Quantitative Structure Activity
Relationships (QSARs) for an alga (Desmodesmus subspicatus), an invertebrate
(Daphnia magna) and a fish (Danio rerio) using the appropriate array of OECD Test
Guidelines. A chronic toxicity QSAR was also determined for the most sensitive
taxon, Desmodesmus. Pure AO spanning the chain lengths of C8 to C16 were tested
individually with trace analytical confirmation of exposures in all tests. The
QSARs were all of high quality (R2 0.92-0.98) with slopes ranging from -0.338 to
0.484. QSARs were then used to normalize toxicity outcomes for a larger,
previously published data set used in HPV, European REACH (Registration,
Evaluation, and Authorization of Chemicals), and peer reviewed publications. Two
additional species, Lemna gibba (macrophyte) and Ankistrodesmus falcatus (alga)
were studied in exposures to dodecyl (C12) AO to provide sufficient taxonomic
diversity to conduct a Species Sensitivity Distribution (SSD) analysis. The SSD
5th percentile hazardous concentration (HC5) to C12 AO was found to be 0.052mg/L
which is similar to an existing AO 28-d, 3-community periphyton community
bioassay normalized to C12 AO (No-observed-effect-concentration or
NOEC=0.152mg/L). The statistical properties of the SSD was probed suggesting that
new studies of additional taxa would be required that were at least 10-fold more
sensitive than the most sensitive taxon to move the HC5 lower by a factor of 3.
The overall AO hazard assessment suggests a large margin of safety relative to
published environmental exposure data.
PMID- 27611220
TI - Impairment of reproduction of adult zebrafish (Danio rerio) by binary mixtures of
environmentally relevant concentrations of triclocarban and inorganic mercury.
AB - Effects of chemical mixtures at environmentally relevant concentrations on
endocrine systems of aquatic organisms are of concern. Triclocarban (TCC) and
inorganic mercury (Hg2+) are ubiquitous in aquatic environments, and are known to
interfere with endocrine pathways via different mechanisms of toxic action.
However, effects of mixtures of the two pollutants on aquatic organisms and
associated molecular mechanisms were unknown. This study examined effects of
binary mixtures of TCC and Hg2+ on histopathological and biochemical alteration
of reproductive organs in zebrafish (Danio rerio) after 21 d exposure. The
results showed that: 1) At concentrations studied, TCC alone caused little effect
on hepatic tissues, but it aggravated lesions in liver caused by Hg2+ via
indirect mechanisms of disturbing homeostasis and altering concentrations of
hormones; 2) Histological lesions were more severe in gonads of individuals,
especially males, exposed to the binary mixture. Exposure to TCC alone (2.5 or
5MUg/L) (measured concentration 140 or 310ng/L) or Hg2+ alone (5MUg/L or 10MUg/L
(measured concentration 367 or 557ng/L) slightly retarded development of oocytes,
whereas co-exposure to nominal concentrations of 5MUg/L TCC and 10MUg /L Hg2+
promoted maturation of oocytes. In males, maturation of sperm was slightly
delayed by exposure to either TCC or Hg2+, while their combinations caused testes
to be smaller and sperm to be fewer compared with fish exposed to either of the
contaminants individually; 3) Lesions observed in fish exposed to binary mixtures
might be due to altered transcription of genes involved in steroidogenesis, such
as cyp19a, 3beta-HSD, cyp17, 17beta-HSD and modulated concentrations of
testosterone and estradiol in blood plasma. The observed results further support
the complexity of toxic responses of fish exposed to lesser concentrations of
binary chemical mixtures. Since it is impossible to collect empirical information
in controlled studies of all possible combinations of toxicants, the application
of omics methods might improve the predictive capabilities of results of single
classes of chemicals.
PMID- 27611219
TI - Impact of CaO, fly ash, sulfur and Na2S on the (im)mobilization and
phytoavailability of Cd, Cu and Pb in contaminated soil.
AB - Soil heavy metals pollution is a serious problem worldwide due to its potential
human health risks through food chain. Therefore, a sustainable solution is
needed to efficiently remediate HMs contaminated soils. Our study aimed to assess
the impact of CaO, fly ash, sulfur, and Na2S on the immobilization of Cd, Cu, and
Pb and their uptake by Chinese cabbage (Brassica rapa chinensis) in a
contaminated soil. The concentration of DTPA-extractable Cd, Cu, and Pb was
significantly decreased as compared to control in treated soil. However, the
solubility of Cd, Cu, and Pb has increased at greater extent in soil system which
favored the uptake of metals in roots and shoots of Chinese cabbage. In general,
Cd uptake was significantly increased in shoots followed by roots as compared to
control. In addition, Cu has also same trend of increased uptake in shoots as
compared to roots. However, the uptake Pb in shoots was considerably increased in
Na2S treated samples whereas roots have shown great potential for Pb uptake in
CaO treated samples as compared to control. Although, sulfur treatments had
efficiently immobilized metals but reduced soil pH to highly acidic level which
restricted the growth of Chinese cabbage in sulfur treated samples. We assume
that sulfur amendment could be applied for immobilization of metals in alkaline
soils rather than acidic soils to achieve better immobilization results. In order
to achieve sustainable phytoextraction of Cd, Cu, and Pb using CaO, FA, and Na2S,
the non-edible hyperaccumulators species are suggested to be investigated in
future studies.
PMID- 27611221
TI - Metal phytoremediation: General strategies, genetically modified plants and
applications in metal nanoparticle contamination.
AB - The accumulation of metals in different environmental compartments poses a risk
to both the environment and biota health. In particular, the continuous increase
of these elements in soil ecosystems is a major worldwide concern.
Phytoremediation has been gaining more attention in this regard. This approach
takes advantage of the unique and selective uptake capabilities of plant root
systems, and applies these natural processes alongside the translocation,
bioaccumulation, and contaminant degradation abilities of the entire plant and,
although it is a relatively recent technology, beginning in the 90's, it is
already considered a green alternative solution to the problem of metal
pollution, with great potential. This review focuses on phytoremediation of
metals from soil, sludge, wastewater and water, the different strategies applied,
the biological and physico-chemical processes involved and the advantages and
limitations of each strategy. Special note is given to the use of transgenic
species and phytoremediation of metallic nanoparticles.
PMID- 27611222
TI - Lithium Ion Pathway within Li7 La3 Zr2 O12 -Polyethylene Oxide Composite
Electrolytes.
AB - Polymer-ceramic composite electrolytes are emerging as a promising solution to
deliver high ionic conductivity, optimal mechanical properties, and good safety
for developing high-performance all-solid-state rechargeable batteries. Composite
electrolytes have been prepared with cubic-phase Li7 La3 Zr2 O12 (LLZO) garnet
and polyethylene oxide (PEO) and employed in symmetric lithium battery cells. By
combining selective isotope labeling and high-resolution solid-state Li NMR, we
are able to track Li ion pathways within LLZO-PEO composite electrolytes by
monitoring the replacement of (7) Li in the composite electrolyte by (6) Li from
the (6) Li metal electrodes during battery cycling. We have provided the first
experimental evidence to show that Li ions favor the pathway through the LLZO
ceramic phase instead of the PEO-LLZO interface or PEO. This approach can be
widely applied to study ion pathways in ionic conductors and to provide useful
insights for developing composite materials for energy storage and harvesting.
PMID- 27611223
TI - Characterization of Antibacterial Activities of Eastern Subterranean Termite,
Reticulitermes flavipes, against Human Pathogens.
AB - The emergence and dissemination of multidrug resistant bacterial pathogens
necessitate research to find new antimicrobials against these organisms. We
investigated antimicrobial production by eastern subterranean termites,
Reticulitermes flavipes, against a panel of bacteria including three multidrug
resistant (MDR) and four non-MDR human pathogens. We determined that the crude
extract of naive termites had a broad-spectrum activity against the non-MDR
bacteria but it was ineffective against the three MDR pathogens Pseudomonas
aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Acinetobacter
baumannii. Heat or trypsin treatment resulted in a complete loss of activity
suggesting that antibacterial activity was proteinaceous in nature. The
antimicrobial activity changed dramatically when the termites were fed with
either heat-killed P. aeruginosa or MRSA. Heat-killed P. aeruginosa induced
activity against P. aeruginosa and MRSA while maintaining or slightly increasing
activity against non-MDR bacteria. Heat-killed MRSA induced activity specifically
against MRSA, altered the activity against two other Gram-positive bacteria, and
inhibited activity against three Gram-negative bacteria. Neither the naive
termites nor the termites challenged with heat-killed pathogens produced
antibacterial activity against A. baumannii. Further investigation demonstrated
that hemolymph, not the hindgut, was the primary source of antibiotic activity.
This suggests that the termite produces these antibacterial activities and not
the hindgut microbiota. Two-dimensional gel electrophoretic analyses of 493
hemolymph protein spots indicated that a total of 38 and 65 proteins were
differentially expressed at least 2.5-fold upon being fed with P. aeruginosa and
MRSA, respectively. Our results provide the first evidence of constitutive and
inducible activities produced by R. flavipes against human bacterial pathogens.
PMID- 27611225
TI - Bilateral internal thoracic artery grafting via T-shaped partial sternotomy in a
patient with terminal tracheostoma.
PMID- 27611227
TI - Referral of patients for pre-implantation genetic diagnosis: A survey of
obstetricians.
AB - BACKGROUND: Pre-implantation genetic diagnosis (PGD) is a molecular diagnostic
technique in which embryos are tested for specific genetic abnormalities to
enable the selection of those unaffected by the condition. Previous Australian
evidence suggested that women who are not informed about PGD by their
obstetrician feel disempowered about not being given this option. AIMS: This
study aimed to explore obstetrician knowledge regarding PGD and identify barriers
to referral. MATERIALS AND METHODS: An invitation to the study with a link to an
online questionnaire was e-mailed by the Royal Australian and New Zealand College
of Obstetricians and Gynaecologists to their members. RESULTS: In total, 372
practising obstetricians responded. Perceptions of their patients' financial
status and ability to access PGD were identified as barriers to referral. There
was variability in referral for PGD and/or genetic services according to the
clinical scenario and in the perceived appropriateness of PGD for different
indications. Obstetricians who had undergone professional development related to
PGD were more likely to discuss PGD than those who had not (chi2 = 6.44; P <
0.01). CONCLUSIONS: The results highlight the need for additional training,
development of educational resources and awareness of appropriate referral
pathways to ensure that those couples who are eligible for PGD are informed.
PMID- 27611224
TI - The Effect of Commonly Used Excipients on the Epithelial Integrity of Human
Cervicovaginal Tissue.
AB - Pharmaceutical excipients are widely used in vaginal drug products. The
epithelial integrity of the cervicovaginal tissue is important for HIV-1
prevention. However, the effects of excipients on cervicovaginal epithelium
remain unknown. This study aims at assessing the effects of vaginal product
excipients on the integrity of human cervicovaginal epithelium and on a lead HIV
prevention antiretroviral drug, tenofovir (TFV). In the current study, nine
excipients commonly used in vaginal formulations were incubated for 6 h with
excised human ectocervical tissue. The effects of the excipients were examined by
measuring the transepithelial electrical resistance (TEER), epithelial
morphology, paracellular/transcellular permeability, and cell viability. The
efficacy of TFV for preventing HIV-1 infection in the ex vivo cultured ectocervix
was also tested. We found that disodium ethyl-enediaminetetraacetate (EDTA),
sorbic acid, and benzoic acid had no effect on the tissue TEER. Butylated
hydroxyanisole, glycerin, propylene glycol, methylparaben, and propylparaben
slightly to moderately decreased tissue TEER, whereas citric acid significantly
decreased the TEER in a time-dependent manner. Tissue morphology observed post
exposure strongly correlated with TEER data; however, a less strong correlation
was observed between paracellular permeability and TEER data after exposure to
different excipients. In addition, treatment with EDTA, methylparaben, and
propylene glycol at tested levels had no effect on the efficacy of TFV in
preventing tissue HIV-1 infection. In conclusion, the combined measurements of
TEER, morphology, permeability, and viability using human cervicovaginal tissue
represent a clinically relevant platform for safety evaluation of excipients and
formulated products for HIV-1 prevention.
PMID- 27611228
TI - A review of electrogenerated chemiluminescent biosensors for assays in biological
matrices.
AB - Electrogenerated chemiluminescence (ECL) is the production of light via electron
transfer reactions between electrochemically produced reagents. ECL-based
biosensors use specific biological interactions to recognize an analyte and
produce a luminescent signal. Biosensors fabricated with novel biorecognition
species have increased the number of analytes detected. Some of these analytes
include peptides, cells, enzymes and nucleic acids. ECL biosensors are selective,
simple, sensitive and have low detection limits. Traditional methods use
ruthenium complexes or luminol to generate ECL. Nanomaterials can be incorporated
into ECL biosensors to improve efficiency, but also represent a new class of ECL
emitters. This article reviews the application of ruthenium complex, luminol and
nanomaterial-based ECL biosensors to making measurements in biological matrices
over the past 4 years.
PMID- 27611229
TI - p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress.
AB - DNA replication initiation is a key event in the cell cycle, which is dependent
on 2 kinases - CDK2 and CDC7. Here we report a novel mechanism in which p53
induces G1 checkpoint and cell cycle arrest by downregulating CDC7 kinase in
response to genotoxic stress. We demonstrate that p53 controls CDC7 stability
post-transcriptionally via miR-192/215 and post-translationally via Fbxw7beta E3
ubiquitin ligase. The p53-dependent pathway of CDC7 downregulation is interlinked
with the p53-p21-CDK2 pathway, as p21-mediated inhibition of CDK2-dependent
phosphorylation of CDC7 on Thr376 is required for GSK3beta-phosphorylation and
Fbxw7beta-dependent degradation of CDC7. Notably, sustained oncogenic high levels
of active CDC7 exert a negative feedback onto p53, leading to unrestrained S
phase progression and accumulation of DNA damage. Thus, p53-dependent control of
CDC7 levels is essential for blocking G1/S cell-cycle transition upon genotoxic
stress, thereby safeguarding the genome from instability and thus representing a
novel general stress response.
PMID- 27611230
TI - Chromatin architecture: A new dimension in the dynamic control of gene
expression.
AB - As the most recent evidence of eukaryotic cell complexity, genome architecture
has astounded the scientific community and prompted a variety of technical and
cognitive challenges. Several technologies have emerged and evidenced the
integration of chromatin packaging and topology, epigenetic processes, and
transcription for the pertinent regulation of gene expression. In the present
addendum we present and discuss some of our recent research, directed toward the
holistic comprehension of the processes by which plants respond to environmental
and developmental stimuli. We propose that the study of genome topology and
genomic interactions is essential for the understanding of the molecular
mechanisms behind a phenotype. Even though our knowledge and understanding of
genome architecture and hierarchy has improved substantially in the last few
years -in Arabidopsis and other eukaryotes -, there is still a long way ahead in
this relatively new field of study. For this, it is necessary to take advantage
of the high resolution of the emerging available techniques, and perform
integrative approaches with which it will be possible to depict the role of
chromatin architecture in the regulation of transcription and ultimately,
physiological processes.
PMID- 27611231
TI - Quantitation of IgG kappa and IgG lambda in the cerebrospinal fluid by sandwich
ELISA method.
AB - IgG kappa and IgG lambda concentrations were quantified in 96 paired CSF and sera
using HevyliteTM antibodies in an in-house developed sandwich ELISA method. In 56
of these samples, the results were compared with a qualitative isoelectric
focusing/affinity-mediated immunoblotting assay for oligoclonal IgG kappa and IgG
lambda. Normal IgG kappa/lambda ratio in the CSF was the same as in serum. In
19/33 patients with intrathecal oligoclonal IgG synthesis, skewed IgG
kappa/lambda ratio was observed (increased in 16 and decreased in 3 cases). The
analysis of light chain composition of intrathecally synthesised immunoglobulins
could contribute to our understanding of intrathecal humoral immune response,
although its diagnostic utility is limited.
PMID- 27611232
TI - During My Residency, I Learned That the Patient Radiation Dose in Fluoroscopy
Depended on Field Size. Now, With Digital Units, the Vendor Says It Does Not. Is
That True?
PMID- 27611234
TI - Intravenous versus inhalational techniques for rapid emergence from anaesthesia
in patients undergoing brain tumour surgery.
AB - BACKGROUND: Brain tumour surgery usually is carried out with the patient under
general anaesthesia. Over past years, both intravenous and inhalational
anaesthetic agents have been used, but the superiority of one agent over the
other is a topic of ongoing debate. Early and rapid emergence from anaesthesia is
desirable for most neurosurgical patients. With the availability of newer
intravenous and inhalational anaesthetic agents, all of which have inherent
advantages and disadvantages, we remain uncertain as to which technique may
result in more rapid early recovery from anaesthesia. OBJECTIVES: To assess the
effects of intravenous versus inhalational techniques for rapid emergence from
anaesthesia in patients undergoing brain tumour surgery. SEARCH METHODS: We
searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue
6) in The Cochrane Library, MEDLINE via Ovid SP (1966 to June 2014) and Embase
via Ovid SP (1980 to June 2014). We also searched specific websites, such as
www.indmed.nic.in, www.cochrane-sadcct.org and www.Clinicaltrials.gov (October
2014). We reran the searches for all databases in March 2016, and when we update
the review, we will deal with the two studies of interest found through this
search that are awaiting classification. SELECTION CRITERIA: We included
randomized controlled trials (RCTs) that compared the use of intravenous
anaesthetic agents such as propofol and thiopentone with inhalational anaesthetic
agents such as isoflurane and sevoflurane for maintenance of general anaesthesia
during brain tumour surgery. Primary outcomes were emergence from anaesthesia
(assessed by time to follow verbal commands, in minutes) and adverse events
during emergence, such as haemodynamic changes, agitation, desaturation, muscle
weakness, nausea and vomiting, shivering and pain. Secondary outcomes were time
to eye opening, recovery from anaesthesia using the Aldrete or Modified Aldrete
score (i.e. time to attain score >= 9, in minutes), opioid consumption, brain
relaxation (as assessed by the surgeon on a 4- or 5-point scale) and
complications of anaesthetic techniques, such as intraoperative haemodynamic
instability in terms of hypotension or hypertension (mmHg), increased or
decreased heart rate (beats/min) and brain swelling. DATA COLLECTION AND
ANALYSIS: We used standardized methods in conducting the systematic review, as
described by the Cochrane Handbook for Systematic Reviews of Interventions. Two
review authors independently extracted details of trial methods and outcome data
from reports of all trials considered eligible for inclusion. We performed all
analyses on an intention-to-treat basis. We used a fixed-effect model when we
found no evidence of significant heterogeneity between studies, and a random
effects model when heterogeneity was likely. For assessments of the overall
quality of evidence for each outcome that included pooled data from RCTs only, we
downgraded the evidence from 'high quality' by one level for serious (or by two
levels for very serious) study limitations (risk of bias), indirectness of
evidence, serious inconsistency, imprecision of effect or potential publication
bias. MAIN RESULTS: We included 15 RCTs with 1833 participants. We determined
that none of the RCTs were of high methodological quality. For our primary
outcomes, pooled results from two trials suggest that time to emergence from
anaesthesia, that is, time needed to follow verbal commands, was longer with
isoflurane than with propofol (mean difference (MD) -3.29 minutes, 95% confidence
interval (CI) -5.41 to -1.18, low-quality evidence), and time to emergence from
anaesthesia was not different with sevoflurane compared with propofol (MD 0.28
minutes slower with sevoflurane, 95% CI -0.56 to 1.12, four studies, low-quality
evidence). Pooled analyses for adverse events suggest lower risk of nausea and
vomiting with propofol than with sevoflurane (risk ratio (RR) 0.68, 95% CI 0.51
to 0.91, low-quality evidence) or isoflurane (RR 0.45, 95% CI 0.26 to 0.78) and
greater risk of haemodynamic changes with propofol than with sevoflurane (RR
1.85, 95% CI 1.07 to 3.17), but no differences in the risk of shivering or pain.
Pooled analyses for brain relaxation suggest lower risk of tense brain with
propofol than with isoflurane (RR 0.88, 95% CI 0.67 to 1.17, low-quality
evidence), but no difference when propofol is compared with sevoflurane. AUTHORS'
CONCLUSIONS: The finding of our review is that the intravenous technique is
comparable with the inhalational technique of using sevoflurane to provide early
emergence from anaesthesia. Adverse events with both techniques are also
comparable. However, we derived evidence of low quality from a limited number of
studies. Use of isoflurane delays emergence from anaesthesia. These results
should be interpreted with caution. Randomized controlled trials based on uniform
and standard methods are needed. Researchers should follow proper methods of
randomization and blinding, and trials should be adequately powered.
PMID- 27611233
TI - Atrial fibrillation in CLL patients treated with ibrutinib. An international
retrospective study.
AB - Atrial fibrillation (AF) occurs in 5-9% of patients treated with ibrutinib for
chronic lymphocytic leukaemia (CLL); the clinical consequences and optimal
management are unclear. We retrospectively studied 56 CLL patients who received
ibrutinib and developed AF. Median time to onset was 3.8 months. AF was
persistent in 35/56 (62%) cases despite treatment. Clinical consequences
included: three episodes of severe cardiac failure (one fatal) and one stroke;
eight non-thrombocytopenic patients (14%) experienced severe bleeding adverse
events. Altogether, ibrutinib was permanently discontinued in 26/56 cases (46%).
Data to guide optimal management are lacking and clinical practice guidelines are
urgently needed.
PMID- 27611235
TI - Empirically derived personality subtyping for predicting clinical symptoms and
treatment response in bulimia nervosa.
AB - OBJECTIVE: Evidence suggests that eating disorder subtypes reflecting under
controlled, over-controlled, and low psychopathology personality traits
constitute reliable phenotypes that differentiate treatment response. This study
is the first to use statistical analyses to identify these subtypes within
treatment-seeking individuals with bulimia nervosa (BN) and to use these
statistically derived clusters to predict clinical outcomes. METHODS: Using
variables from the Dimensional Assessment of Personality Pathology-Basic
Questionnaire, K-means cluster analyses identified under-controlled, over
controlled, and low psychopathology subtypes within BN patients (n = 80) enrolled
in a treatment trial. Generalized linear models examined the impact of
personality subtypes on Eating Disorder Examination global score, binge eating
frequency, and purging frequency cross-sectionally at baseline and longitudinally
at end of treatment (EOT) and follow-up. In the longitudinal models, secondary
analyses were conducted to examine personality subtype as a potential moderator
of response to Cognitive Behavioral Therapy-Enhanced (CBT-E) or Integrative
Cognitive-Affective Therapy for BN (ICAT-BN). RESULTS: There were no baseline
clinical differences between groups. In the longitudinal models, personality
subtype predicted binge eating (p = 0.03) and purging (p = 0.01) frequency at EOT
and binge eating frequency at follow-up (p = 0.045). The over-controlled group
demonstrated the best outcomes on these variables. In secondary analyses, there
was a treatment by subtype interaction for purging at follow-up (p = 0.04), which
indicated a superiority of CBT-E over ICAT-BN for reducing purging among the over
controlled group. DISCUSSION: Empirically derived personality subtyping appears
to be a valid classification system with potential to guide eating disorder
treatment decisions. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017;
50:506-514).
PMID- 27611236
TI - PATI: Patient accessed tailored information: A pilot study to evaluate the effect
on preoperative breast cancer patients of information delivered via a mobile
application.
AB - OBJECTIVES: The information needs of cancer patients are highly variable.
Literature suggests an improved ability to modulate personalised stress,
increased patient involvement with decision making, greater satisfaction with
treatment choices and reduced anxiety levels in cancer patients who have access
to information. The aim of this project was to evaluate the effects of a mobile
information application on anxiety levels of patients undergoing surgery for
breast cancer. MATERIALS AND METHODS: An application was developed for use with
Apple iPad containing information on basic breast cancer biology, different
treatments used and surgical techniques. Content and face validity studies were
performed. A randomized control trial was designed, with a 1:2 allocation. Data
collected include basic demographics and type of surgery. Questionnaires used
included: the HADS, Mini-MAC, information technology familiarity and information
satisfaction. RESULTS: A total of 39 women participated. 13 women had access to
an iPad containing additional information and 26 women acted as controls. The
mean age was 54 and technology familiarity was similar among both groups. Anxiety
and depression scores at seven days were significantly lower in control patients
without access to the additional information provided by the mobile application
(p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast
cancer patients is both multifactorial and significant, with anxiety levels
directly correlating with reduced quality of life. Intuitively, information
should improve anxiety levels, however, we have demonstrated that surgical
patients with less information reported significantly lower anxiety. We advise
the thorough testing and auditing of information initiatives before deployment.
PMID- 27611237
TI - Immediate expander/implant breast reconstruction followed by post-mastectomy
radiotherapy for breast cancer: Aesthetic, surgical, satisfaction and quality of
life outcomes in women with high-risk breast cancer.
AB - BACKGROUND: Immediate tissue expander/implant-based breast reconstruction (BR) is
often avoided when post-mastectomy radiotherapy (PMRT) is planned due to concerns
about high complication rates and poor aesthetic outcomes. This study evaluated
surgical, aesthetic and quality of life (QoL) outcomes in women undergoing
immediate implant-based BR (IIBR) followed by PMRT. METHODS: Participants were
recruited at least six months after completing the final stage of BR. They
completed validated on-line questionnaires assessing satisfaction, QoL, distress,
body image and regret. Aesthetic outcomes were rated by their operating surgeon
through clinical examination and assessed by an independent surgeon using
photographs. RESULTS: Forty-seven participants completed questionnaires and
reported good outcomes for QoL (FACT-B = 115; TOI = 73), satisfaction (Breast-Q),
distress (Impact of Events scale <4.8 all subscales) and body image (Body Image
scale), with a low score on the Decisional Regret scale (mean 12.1). Aesthetic
outcomes were rated fair-to-good (Kroll scale). The surgical complication rate
was low (expander/implant loss rate 6.4%, wound infection 10.6%, seroma 4.1%). At
follow-up, 33 (70.2%) participants retained their permanent implant and 12
(25.5%) converted to a TRAM or DIEP flap; there were two LD flaps. CONCLUSION:
This study demonstrated acceptable cosmetic results, high patient satisfaction
and low complication rates. It provides evidence that women are willing to accept
the potential risks of IIBR in exchange for its benefits including enhanced body
image during chemotherapy and PMRT and the possible avoidance of more complicated
and costly delayed autologous BR. The results support the importance of access to
BR, even in women with high-risk disease.
PMID- 27611240
TI - Cloning and characterization of TaMBD6 homeologues encoding methyl-CpG-binding
domain proteins in wheat.
AB - DNA methylation is a major epigenetic marker in plants that plays a crucial role
in transcriptional and developmental regulation. The DNA methylation 'code' is
thought to be 'read' by a set of proteins containing methyl-CpG-binding domain
(MBD). However, little is known about MBD genes in common wheat (Triticum
aestivum L.). Here, we report the isolation and characterization of TaMBD6 and
its homeologues (TaMBD6_A, TaMBD6_B, and TaMBD6_D) in hexaploid wheat. The cDNA
was quite different among the three homeologues and InDel mutations were detected
in 5'-UTR and coding region. Two types of TRs (tandem repeats) -- TR1 (57 bp) and
TR2 (39 bp) -- occurred in the coding region. TaMBD6_B harbored five copies of
TR1 and two copies of TR2. In contrast, TaMBD6_A lacked 30 bp between the 2nd and
3rd copy of TR1, while TaMBD6_D was missing two copies of TR1 but had three
copies of TR2. TaMBD6_A, TaMBD6_B, and TaMBD6_D encoded 435, 446, and 420 amino
acids, respectively. Structural analysis of TaMBD6 protein indicated that each of
the three homeologues had an identical MBD domain at the N-terminal, as well as a
typical nuclear localization signal. Although genomics analysis showed that two
introns were included, the length of the first intron varied from 3100 bp to 3471
bp and their sequences were very different. Expression analysis demonstrated that
the transcription level of TaMBD6 began to increase gradually in developing
grains at 15 days after pollination while decreasing significantly in endosperm
and embryo tissues during germination. Expression of TaMBD6 appeared to be
positively correlated with starch metabolism in the endosperm but was negatively
correlated with embryo formation and sprouting. We were also interested to learn
that TaMBD6 homeologues were differentially expressed in developing wheat plants
and that their expression patterns were variously affected by vernalization
treatment. Further investigation revealed that TaMBD6 was induced by prolonged
chilling, indicating that the protein is potentially involved in regulating the
developmental transition from vegetative to reproductive stages. Although the
homeologues generally showed similar differential expression patterns, TaMBD6_D
and TaMBD6_B contribute more to the processes of grain development and
germination while TaMBD6_A is predominant in mature plants.
PMID- 27611239
TI - Lentivirus Mediated Correction of Artemis-Deficient Severe Combined
Immunodeficiency.
AB - During B and T lymphocyte maturation, V(D)J recombination is initiated by
creation of DNA double-strand breaks. Artemis is an exonuclease essential for
their subsequent repair by nonhomologous end-joining. Mutations in DCLRE1C, the
gene encoding Artemis, cause T-B-NK+ severe combined immunodeficiency (ART-SCID)
and also confer heightened sensitivity to ionizing radiation and alkylating
chemotherapy. Although allogeneic hematopoietic cell transplantation can treat
ART-SCID, conditioning regimens are poorly tolerated, leading to early mortality
and/or late complications, including short stature, endocrinopathies, and dental
aplasia. However, without alkylating chemotherapy as preconditioning, patients
usually have graft rejection or limited T cell and no B cell recovery. Thus,
addition of normal DCLRE1C cDNA to autologous hematopoietic stem cells is an
attractive strategy to treat ART-SCID. We designed a self-inactivating lentivirus
vector containing human Artemis cDNA under transcriptional regulation of the
human endogenous Artemis promoter (AProArt). Fibroblasts from ART-SCID patients
transduced with AProArt lentivirus showed correction of radiosensitivity.
Mobilized peripheral blood CD34+ cells from an ART-SCID patient as well as
hematopoietic stem cells from Artemis-deficient mice demonstrated restored T and
B cell development following AProArt transduction. Murine hematopoietic cells
transduced with AProArt exhibited no increase in replating potential in an in
vitro immortalization assay, and analysis of AProArt lentivirus insertions showed
no predilection for sites that could activate oncogenes. These efficacy and
safety findings support institution of a clinical trial of gene addition therapy
for ART-SCID.
PMID- 27611242
TI - The love of money results in objectification.
AB - Objectification, which refers to the treatment of others as objectlike things,
has long been observed in capitalism. While the negative impact of money on
interpersonal harmony has been well documented, the social cognitive processes
that underlie them are relatively unknown. Across four studies, we explored
whether the love of money leads to objectification, while controlling for social
power and status. In Study 1, the love and importance attached to money
positively predicted the tendency to construe social relationships based on
instrumentality. In Study 2, the likelihood to favour a target of instrumental
use was increased by momentarily activating an affective state of being rich.
Temporarily heightening the motivation for money further resulted in deprivation
of mental capacities of irrelevant others, including humans (Study 3) and animals
(Study 4). This lack of perceived mental states partially mediated the effects of
money on subsequent immoral behaviour (Study 4). The findings are the first to
reveal the role of objectification as a potential social cognitive mechanism for
explaining why money often harms interpersonal harmony.
PMID- 27611243
TI - Identification of the sex-determining region in flathead grey mullet (Mugil
cephalus).
AB - Elucidation of the sex-determination mechanism in flathead grey mullet (Mugil
cephalus) is required to exploit its economic potential by production of
genetically determined monosex populations and application of hormonal treatment
to parents rather than to the marketed progeny. Our objective was to construct a
first-generation linkage map of the M. cephalus in order to identify the sex
determining region and sex-determination system. Deep-sequencing data of a single
male was assembled and aligned to the genome of Nile tilapia (Oreochromis
niloticus). A total 245 M. cephalus microsatellite markers were designed,
spanning the syntenic tilapia genome assembly at intervals of 10 Mb. In the
mapping family of full-sib progeny, 156 segregating markers were used to
construct a first-generation linkage map of 24 linkage groups (LGs),
corresponding to the number of chromosomes. The linkage map spanned approximately
1200 cM with an average inter-marker distance of 10.6 cM. Markers segregating on
LG9 in two independent mapping families showed nearly complete concordance with
gender (R2 = 0.95). The sex determining locus was fine mapped within an interval
of 8.6 cM on LG9. The sex of offspring was determined only by the alleles
transmitted from the father, thus indicating an XY sex-determination system.
PMID- 27611241
TI - Involvement of dehydrins in 24-epibrassinolide-induced protection of wheat plants
against drought stress.
AB - In this study, we performed a comparative analysis of the physiological and
biochemical parameters of wheat cultivars with contrasting drought resistance,
drought-resistant Omskaya 35 (O-35) and less drought-resistant Salavat Yulaev
(SYu), during 7-day germination under drought stress simulated by 5% mannitol. In
addition, we evaluated the effectiveness of pre-sowing seed treatment with 0.4
MUM 24-epibrassinolide (EBR) used to increase the resistance of plants of both
cultivars to drought stress. It was revealed that mannitol has caused significant
changes in the hormonal balance of the plants of both cultivars, associated with
abscisic acid (ABA) accumulation and decrease in the contents of indoleacetic
acid (IAA) and cytokinins (CKs). It should be noted that more dramatic changes in
the content of phytohormones were characteristic for seedlings of SYu cultivar,
which was reflected in a stronger growth inhibition of these plants. Pretreatment
with EBR mitigated the negative effect of drought on the hormonal status and
growth of seedlings during their germination. Furthermore, we found that drought
caused accumulation of dehydrin (DHN) proteins, especially of low molecular
weight DHNs, whose abundance was 2.5 times greater in O-35 cultivar than in SYu
plants. EBR-pretreated plants of both cultivars were characterized by the
additional accumulation of DHNs, indicating their involvement in the development
of the EBR-induced wheat drought resistance. The use of fluridone allowed us to
demonstrate ABA-dependent and ABA-independent pathways of regulation of low
molecular mass dehydrins accumulation by EBR in wheat plants of both cultivars
under drought conditions.
PMID- 27611245
TI - Biodistribution of Antibody-MS2 Viral Capsid Conjugates in Breast Cancer Models.
AB - A variety of nanoscale scaffolds, including virus-like particles (VLPs), are
being developed for biomedical applications; however, little information is
available about their in vivo behavior. Targeted nanoparticles are particularly
valuable as diagnostic and therapeutic carriers because they can increase the
signal-to-background ratio of imaging agents, improve the efficacy of drugs, and
reduce adverse effects by concentrating the therapeutic molecule in the region of
interest. The genome-free capsid of bacteriophage MS2 has several features that
make it well-suited for use in delivery applications, such as facile production
and modification, the ability to display multiple copies of targeting ligands,
and the capacity to deliver large payloads. Anti-EGFR antibodies were conjugated
to MS2 capsids to construct nanoparticles targeted toward receptors overexpressed
on breast cancer cells. The MS2 agents showed good stability in physiological
conditions up to 2 days and specific binding to the targeted receptors in in
vitro experiments. Capsids radiolabeled with 64Cu isotopes were injected into
mice possessing tumor xenografts, and both positron emission tomography-computed
tomography (PET/CT) and scintillation counting of the organs ex vivo were used to
determine the localization of the agents. The capsids exhibit surprisingly long
circulation times (10-15% ID/g in blood at 24 h) and moderate tumor uptake (2-5%
ID/g). However, the targeting antibodies did not lead to increased uptake in vivo
despite in vitro enhancements, suggesting that extravasation is a limiting factor
for delivery to tumors by these particles.
PMID- 27611246
TI - Replicative Bypass of O2-Alkylthymidine Lesions in Vitro.
AB - DNA alkylation represents a major type of DNA damage and is generally unavoidable
due to ubiquitous exposure to various exogenous and endogenous sources of
alkylating agents. Among the alkylated DNA lesions, O2-alkylthymidines (O2
alkyldT) are known to be persistent and poorly repaired in mammalian systems and
have been shown to accumulate in the esophagus, lung, and liver tissue of rats
treated with tobacco-specific N-nitrosamines, i.e., 4-(methylnitrosamino)-1-(3
pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). In this study, we
assessed the replicative bypass of a comprehensive set of O2-alkyldT lesions,
with the alkyl group being a Me, Et, nPr, iPr, nBu, iBu, or sBu, in template DNA
by conducting primer extension assays with the use of major translesion synthesis
DNA polymerases. The results showed that human Pol eta and, to a lesser degree,
human Pol kappa, but not human polymerase iota or yeast polymerase zeta, were
capable of bypassing all O2-alkyldT lesions and extending the primer to generate
full-length replication products. Data from steady-state kinetic measurements
showed that human Pol eta exhibited high frequencies of misincorporation of dCMP
opposite those O2-alkyldT lesions bearing a longer straight-chain alkyl group.
However, the nucleotide misincorporation opposite branched-chain lesions was not
selective, with dCMP, dGMP, and dTMP being inserted at similar efficiencies,
though the total frequencies of nucleotide misincorporation opposite the branched
chain lesions differed and followed the order of O2-iPrdT > O2-iBudT > O2-sBudT.
Together, the results from the present study provided important knowledge about
the effects of the length and structure of the alkyl group in the O2-alkyldT
lesions on the fidelity and efficiency of DNA replication mediated by human Pol
eta.
PMID- 27611299
TI - Hydrogen Evolution Catalyzed by Cu2WS4 at Liquid-Liquid Interfaces.
AB - The present study reports, for the first time, both a facile synthesis for
ternary Cu2WS4 nanocubes, which were synthesized by a simple and low-cost hot
injection method, and the hydrogen evolution reaction at a biomembrane-like
polarized water/1,2-dichloroethane interface catalyzed by Cu2WS4 nanocubes. The
rate of hydrogen evolution reaction is increased by about 1000 times by using
Cu2WS4 nanocubes when compared to an uncatalyzed reaction.
PMID- 27611298
TI - Effect of Bovine Lactoferrin Treatment Followed by Acute Stress on the IgA
Response in Small Intestine of BALB/c Mice.
AB - Secretory IgA (SIgA) has a pivotal role in gut homeostasis, which can be
disturbed by stress. SIgA is formed by IgA-dimers (associated by the J-chain) and
the secretory component, a protein derivative of polymeric immunoglobulin
receptor (pIgR). Given the gut immuno-modulatory properties of bovine lactoferrin
(bLf), the aim of this study was to compare, after bLf treatment followed by
acute stress, the IgA response and IgA-associated parameters in proximal versus
distal small intestine. Male BALB/c mice (n = 6) were orally treated with bLf
(50, 500, and 5000 MUg) for 7 days, then stressed by immobilization for 1 h, and
sacrificed. In proximal and distal segments, levels were determined of IgA in gut
secretions (enzyme-linked immunosorbent assay [ELISA]), the alpha-/J-chain and
pIgR proteins in epithelial cells (Western-blot), and mRNA expression of the
alpha-/J-chain, pIgR, and interleukins (ILs) in mucosa (RT-PCR). Data were
compared by two-way analysis of variance (ANOVA) (significance at P < 0.05).
Under acute stress, bLf triggered higher levels of IgA, SIgA, and anti-bLf-IgA as
well as greater mRNA expression of pIgR, IL-4, and IL-6 (500 ug) in proximal
intestine, while inducing higher levels of the total IgA, alpha-/J-chain, and
pIgR proteins as well as greater mRNA expression of the alpha-chain and IL-4
(5000 ug) in distal intestine. Compared to unstressed/bLf-untreated mice, plasma
corticosterone (a stress biomarker, measured by ELISA) increased in stressed/bLf
treated (0, 50 and 500 ug) and unstressed/bLf-treated (5000 ug) mice. The
interplay of corticosterone with gut neuroendocrine factors may have elicited
signals creating anti-inflammatory conditions for an IgA-response profile in each
intestinal region, according to the bLf concentration administered.
PMID- 27611300
TI - Oral Health in Electroconvulsive Therapy: A Neglected Topic.
AB - Psychiatric medications may have serious and untoward adverse effects such as
blurred vision, restlessness, agranulocytosis, muscle rigidity, and tremors. When
compared to medications, electroconvulsive therapy (ECT) is becoming a more
acceptable treatment due to its efficacy, tolerability, and minimal adverse
effect profile. Oral trauma can be an ECT-related adverse effect. We reviewed the
published literature on oral health and dental protection in patients undergoing
ECT, and found that there are deficits in all guidelines on dental protection
during ECT. Dental assessment and treatment before and after ECT is warranted.
Given the increased risk of poor oral health in psychiatric patients, and the
continued evolution of ECT as a mainstay treatment, it is important that studies
be conducted to determine the optimal method of oral protection. If adequate care
can be ensured, the risks of ECT-induced oral trauma will be minimized.
PMID- 27611301
TI - Actigraphy in Patients With Major Depressive Disorder Undergoing Repetitive
Transcranial Magnetic Stimulation: An Open Label Pilot Study.
AB - BACKGROUND: The effects of repetitive transcranial magnetic stimulation (rTMS) on
physical activity and sleep patterns in individuals with major depressive
disorder (MDD) remain unclear. METHOD: We examined the effects of rTMS treatment
on the rest-activity cycle and sleep disturbances in MDD. In this open-label
pilot study, 14 patients with medication-resistant MDD underwent 10 rTMS sessions
over the bilateral dorsolateral prefrontal cortex. In addition to Hamilton
Depression Rating Scale and Pittsburgh Sleep Quality Index scores, waist
actigraphy was used to evaluate alterations in the rest-activity cycle over the
course of rTMS treatments. Actigraphic data were evaluated at baseline and in the
first (rTMS sessions 1-3), second (rTMS sessions 4-7), and third (rTMS sessions 8
10) sections. RESULTS: Although Hamilton Depression Rating Scale and Pittsburgh
Sleep Quality Index scores were significantly improved by rTMS, sleep variables
assessed by actigraphy did not show significant changes. However, post hoc tests
indicated a significant increase in mean steps per day between the baseline and
first section time points (P = 0.014; t13 = -2.316). CONCLUSIONS: Our data
indicated that a daytime physical activity response to rTMS occurred in early
sessions, whereas subjective symptom improvements were consistent across all
sessions. Future double-blind placebo-controlled studies assessing the effects of
rTMS on the rest-activity cycle and sleep disturbances in MDD are warranted.
PMID- 27611303
TI - Outcome scores in status epilepticus - predicting the complex clinical situation.
PMID- 27611302
TI - Improvement of the BALB/c-3T3 cell transformation assay: a tool for investigating
cancer mechanisms and therapies.
AB - The identification of cancer preventive or therapeutic substances as well as
carcinogenic risk assessment of chemicals is nowadays mostly dependent on animal
studies. In vitro cell transformation assays mimic different stages of the in
vivo neoplastic process and represent an excellent alternative to study
carcinogenesis and therapeutic options. In the BALB/c-3T3 two-stage
transformation assay cells are chemically transformed by treatment with MCA and
TPA, along with the final Giemsa staining of morphological aberrant foci. In
addition to the standard method we can show, that it is possible to apply other
chemicals in parallel to identify potential preventive or therapeutic substances
during the transformation process. Furthermore, we successfully combined the
BALB/c cell transformation assay with several endpoint applications for protein
analysis (immunoblot, subcellular fractionation and immunofluorescence) or energy
parameter measurements (glucose and oxygen consumption) to elucidate cancer
mechanisms in more detail. In our opinion the BALB/c cell transformation assay
proves to be an excellent model to investigate alterations in key proteins or
energy parameters during the different stages of transformation as well as
therapeutic substances and their mode of action.
PMID- 27611304
TI - Bruxism and dental implant failures: a multilevel mixed effects parametric
survival analysis approach.
AB - Recent studies have suggested that the insertion of dental implants in patients
being diagnosed with bruxism negatively affected the implant failure rates. The
aim of the present study was to investigate the association between the bruxism
and the risk of dental implant failure. This retrospective study is based on 2670
patients who received 10 096 implants at one specialist clinic. Implant- and
patient-related data were collected. Descriptive statistics were used to describe
the patients and implants. Multilevel mixed effects parametric survival analysis
was used to test the association between bruxism and risk of implant failure
adjusting for several potential confounders. Criteria from a recent international
consensus (Lobbezoo et al., J Oral Rehabil, 40, 2013, 2) and from the
International Classification of Sleep Disorders (International classification of
sleep disorders, revised: diagnostic and coding manual, American Academy of Sleep
Medicine, Chicago, 2014) were used to define and diagnose the condition. The
number of implants with information available for all variables totalled 3549,
placed in 994 patients, with 179 implants reported as failures. The implant
failure rates were 13.0% (24/185) for bruxers and 4.6% (155/3364) for non-bruxers
(P < 0.001). The statistical model showed that bruxism was a statistically
significantly risk factor to implant failure (HR 3.396; 95% CI 1.314, 8.777; P =
0.012), as well as implant length, implant diameter, implant surface, bone
quantity D in relation to quantity A, bone quality 4 in relation to quality 1
(Lekholm and Zarb classification), smoking and the intake of proton pump
inhibitors. It is suggested that the bruxism may be associated with an increased
risk of dental implant failure.
PMID- 27611306
TI - Correction: Older Adults Looking for a Job through Employment Support System in
Tokyo.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159713.].
PMID- 27611305
TI - A subset of RAB proteins modulates PP2A phosphatase activity.
AB - Protein phosphatase 2A (PP2A) is one of the most abundant serine-threonine
phosphatases in mammalian cells. PP2A is a hetero-trimeric holoenzyme
participating in a variety of physiological processes whose deregulation is often
associated to cancer. The specificity and activity of this phosphatase is tightly
modulated by a family of regulatory B subunits that dock the catalytic subunit to
the substrates. Here we characterize a novel and unconventional molecular
mechanism controlling the activity of the tumor suppressor PP2A. By applying a
mass spectrometry-based interactomics approach, we identified novel PP2A
interacting proteins. Unexpectedly we found that a significant number of RAB
proteins associate with the PP2A scaffold subunit (PPP2R1A), but not with the
catalytic subunit (PPP2CA). Such interactions occur in vitro and in vivo in
specific subcellular compartments. Notably we demonstrated that one of these RAB
proteins, RAB9, competes with the catalytic subunit PPP2CA in binding to PPP2R1A.
This competitive association has an important role in controlling the PP2A
catalytic activity, which is compromised in several solid tumors and leukemias.
PMID- 27611308
TI - Response to Tomoyuki Kawada, MD: Smoking, Systolic Blood Pressure, Fasting Plasma
Glucose and Progression of Carotid Atherosclerosis.
PMID- 27611307
TI - Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size
of Amino Acid by Decreasing Expression of Specific Transporters in the Small
Intestine.
AB - Dietary protein restriction is not only beneficial to health and longevity in
humans, but also protects against air pollution and minimizes feeding cost in
livestock production. However, its impact on amino acid (AA) absorption and
metabolism is not quite understood. Therefore, the study aimed to explore the
effect of protein restriction on nitrogen balance, circulating AA pool size, and
AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 +/- 1.5 kg
were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial.
Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal
AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows
weighting 22.7 +/- 1.3 kg were surgically fitted with catheters in the portal and
jejunal veins as well as the carotid artery and assigned to a diet containing 14
or 18% CP. A series of blood samples were collected before and after feeding for
determining the pool size of circulating AA and AA absorption in the portal vein,
respectively. Protein restriction did not sacrifice body weight gain and protein
retention, since nitrogen digestibility was increased as dietary protein content
reduced. However, the pool size of circulating AA except for lysine and
threonine, and most AA flux through the portal vein were reduced in pigs fed the
low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was
stimulated, but the expression of the neutral and cationic AA transporter systems
was depressed. These results evidenced that protein restriction with essential AA
balanced diets, decreased AA absorption and reduced circulating AA pool size.
Increased expression of small intestinal peptide transporter PepT-1 could not
compensate for the depressed expression of jejunal AA transporters for AA
absorption.
PMID- 27611309
TI - Cigarette Smoking Condensate Disrupts Endoplasmic Reticulum-Golgi Network
Homeostasis Through GOLPH3 Expression in Normal Lung Epithelial Cells.
AB - INTRODUCTION: Cigarette smoke (CS) is associated with a broad range of diseases
including lung cancer. Many researchers have suggested that cigarette smoke
condensate (CSC) may be more toxic compared to cigarette smoke extract (CSE)
because CSC contains the lipid-soluble faction of smoke while CSE contains the
hydrophilic or gas phase. The aim of this research is to investigate the effects
of CSC on the disruption of endoplasmic reticulum (ER)-Golgi homeostasis in
normal lung epithelial cells. METHODS: CS was generated according to the ISO 3308
method. To ascertain the mechanistic effects of CSC on lung toxicity, normal lung
epithelial cells of the cell line 16HBE14o- were treated with CSC (0.1mg/mL) for
48 hours. The toxic effects of CSC on ER-Golgi homeostasis and GOLPH3 expression
were observed through diverse molecular tools including transmission electron
microscope analysis. RESULTS: Our results demonstrated that CSC treatment
increased reactive oxygen species generation in lung cells and led to the
alteration of ER-Golgi homeostasis in conjunction with increased autophagy. In
particular, GOLPH3, known as an oncogene and a marker protein for the trans-Golgi
network, was upregulated in CSC-treated cells. GOLPH3 protein overexpression was
also confirmed in the lungs of human lung cancer patients as well as NNK-treated
mice. CONCLUSION: Our study revealed that CSC caused lung damage through the
disruption of ER-Golgi homeostasis and autophagy induction. The expression level
of the trans-Golgi marker protein GOLPH3 could serve as a reliable bio-indicator
for CS-related lung cancer. IMPLICATIONS: CS is a harmful factor in the
development of many diseases including cancer. In this research, we demonstrated
that CSC treatment led to malfunction of the ER-Golgi network, with the disrupted
ER and Golgi causing GOLPH3 overexpression and abnormal autophagy accumulation.
In addition, although the value of GOLPH3 as a predictor remains to be fully
elucidated, our data suggest that GOLPH3 levels may be a novel prognostic
biomarker of tobacco related lung disease.
PMID- 27611312
TI - DyHAP: Dynamic Hybrid ANFIS-PSO Approach for Predicting Mobile Malware.
AB - To deal with the large number of malicious mobile applications (e.g. mobile
malware), a number of malware detection systems have been proposed in the
literature. In this paper, we propose a hybrid method to find the optimum
parameters that can be used to facilitate mobile malware identification. We also
present a multi agent system architecture comprising three system agents (i.e.
sniffer, extraction and selection agent) to capture and manage the pcap file for
data preparation phase. In our hybrid approach, we combine an adaptive neuro
fuzzy inference system (ANFIS) and particle swarm optimization (PSO). Evaluations
using data captured on a real-world Android device and the MalGenome dataset
demonstrate the effectiveness of our approach, in comparison to two hybrid
optimization methods which are differential evolution (ANFIS-DE) and ant colony
optimization (ANFIS-ACO).
PMID- 27611311
TI - The Association Between Treatment Adherence to Nicotine Patches and Smoking
Cessation in Pregnancy: A Secondary Analysis of a Randomized Controlled Trial.
AB - INTRODUCTION: In nonpregnant "quitters," adherence to nicotine replacement
therapy (NRT) increases smoking cessation. We investigated relationships between
adherence to placebo or NRT patches and cessation in pregnancy, including an
assessment of reverse causation and whether any adherence: cessation relationship
is moderated when using nicotine or placebo patches. METHODS: Using data from
1050 pregnant trial participants, regression models investigated associations
between maternal characteristics, adherence and smoking cessation. RESULTS:
Adherence during the first month was associated with lower baseline cotinine
concentrations (beta -0.08, 95% confidence interval [CI] -0.15 to -0.01) and
randomization to NRT (beta 2.59, 95% CI 1.50 to 3.68). Adherence during both
treatment months was associated with being randomized to NRT (beta 0.51, 95% CI
0.29 to 0.72) and inversely associated with higher nicotine dependence. Adherence
with either NRT or placebo was associated with cessation at 1 month (odds ratio
[OR] 1.11, 95% CI 1.08 to 1.13) and delivery (OR 1.06, 95% CI 1.03 to 1.09), but
no such association was observed in the subgroup where reverse causation was not
possible. Amongst all women, greater adherence to nicotine patches was associated
with increased cessation (OR 2.47, 95% CI 1.32 to 4.63) but greater adherence to
placebo was not (OR 0.98, 95% CI: 0.44 to 2.18). CONCLUSION: Women who were more
adherent to NRT were more likely to achieve abstinence; more nicotine dependent
women probably showed lower adherence to NRT because they relapsed to smoking
more quickly. The interaction between nicotine-containing patches and adherence
for cessation suggests that the association between adherence with nicotine
patches and cessation may be partly causal. IMPLICATIONS: This study used placebo
randomized controlled trial data to investigate both associations between women's
characteristics and adherence to NRT patch treatment, and the relationship
between adherence to NRT patch treatment and odds of cessation in pregnant
quitters. Greater adherence was seen with NRT patches, and greater adherence with
NRT patches increased the odds of smoking cessation. A likely explanation for
findings is that NRT patches, if used sufficiently, may be effective for at least
some pregnant women who try to stop smoking. Trials testing interventions which
encourage women's adherence to higher dose NRT are indicated.
PMID- 27611310
TI - CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine
Receptor Upregulation.
AB - INTRODUCTION: Tobacco smoking leads to increased numbers of beta2*-containing
nicotinic acetylcholine receptors (beta2*-nAChRs) throughout the brain, which
return to nonsmoker levels over extended abstinence. The goal of the current
study was to determine whether the degree of tobacco smoking-induced changes in
beta2*-nAChR availability is genetically influenced. METHODS: In this study, 113
European Americans participated in one or two [(123)I]5-IA-85380 single photon
emission computed tomography (SPECT) brain scans. Smokers (n = 58) participated
in one scan at 7-9 days of abstinence and those who remained abstinent (n = 27)
were imaged again at 6-8 weeks of abstinence. Age- and sex-matched nonsmokers (n
= 55) participated in one scan. Blood samples were collected for DNA analysis and
genotyped for single nucleotide polymorphisms (SNPs) in the CHRNA4 and ANKK1 gene
loci. beta2*-nAChR availability was measured in the thalamus, striatum, cortical
regions, and cerebellum. RESULTS: The CHRNA4 SNP rs2236196 and ANKK1 SNP
rs4938015 were associated with significantly higher cerebellar and cortical
beta2*-nAChR availability in smokers versus nonsmokers for specific genotypes.
There were no significant differences by carrier status in the change in beta2*
nAChR availability in smokers from 7-9 days to 6-8 weeks of abstinence.
CONCLUSION: This study provides evidence for genetic regulation of tobacco
smoking-induced changes in beta2*-nAChR availability and suggests that beta2*
nAChR availability could be an endophenotype mediating influences of CHRNA4
variants on nicotine dependence. These results highlight individual differences
in the neurochemistry of nicotine dependence and may suggest the need for
individualized programs for smoking cessation. IMPLICATIONS: This study
demonstrates genetic regulation of smoking-induced changes in beta2*-nAChRs
throughout the brain and highlights the need for personalized programs for
smoking cessation.
PMID- 27611313
TI - Identifying Risk and Protective Factors in Recidivist Juvenile Offenders: A
Decision Tree Approach.
AB - Research on juvenile justice aims to identify profiles of risk and protective
factors in juvenile offenders. This paper presents a study of profiles of risk
factors that influence young offenders toward committing sanctionable antisocial
behavior (S-ASB). Decision tree analysis is used as a multivariate approach to
the phenomenon of repeated sanctionable antisocial behavior in juvenile offenders
in Spain. The study sample was made up of the set of juveniles who were charged
in a court case in the Juvenile Court of Almeria (Spain). The period of study of
recidivism was two years from the baseline. The object of study is presented,
through the implementation of a decision tree. Two profiles of risk and
protective factors are found. Risk factors associated with higher rates of
recidivism are antisocial peers, age at baseline S-ASB, problems in school and
criminality in family members.
PMID- 27611316
TI - A functional variant of ATG16L2 is associated with Crohn's disease in the Chinese
population.
AB - AIM: To determine whether genetic polymorphism of the ATG16L2 gene is
functionally associated with the incidence of Crohn's disease (CD) in the Chinese
population. METHOD: The single nucleotide polymorphism (SNP) rs11235604 of the
ATG16L2 gene was genotyped in 363 patients with CD and 486 healthy volunteers
from the Chinese Han population. The distributions of the genotype and allele
frequency were compared between patients and controls by the chi-square test. The
mRNA expression of ATG16L2 in T cells was evaluated by real-time PCR. Comparisons
of mRNA expression of ATG16L2 between patients and controls and between patients
with genotype CC and genotype CT/TT were performed with the Student's t-test.
RESULTS: Compared with the controls, patients were found to have a significantly
higher proportion of genotype TT (5.5% vs 2.5%, P = 0.04). Allele T was the risk
allele for the disease (16.3% vs 12.3%, P = 0.02), with an odds ratio of 1.31
(95% CI 1.04-1.67). The ATG16L2 mRNA of the patients was significantly reduced
when compared with the controls (0.0044 +/- 0.0018 vs 0.0064 +/- 0.0023, P <
0.001). Patients with genotype TT/CT had a significant lower level of ATG16L2
mRNA than patients with genotype CC (0.0036 +/- 0.0016 vs 0.0053 +/- 0.0028, P =
0.005). CONCLUSIONS: ATG16L2 is a susceptibility gene for CD in the Chinese
population. The rs11235604 SNP is remarkably associated with downregulation of
the expression of ATG16L2. Further investigation into the gene's function is
warranted for a comprehensive knowledge of the contribution of the variant to the
development of CD.
PMID- 27611314
TI - rBmalphaTX14 Increases the Life Span and Promotes the Locomotion of
Caenorhabditis Elegans.
AB - The scorpion has been extensively used in various pharmacological profiles or as
food supplies. The exploration of scorpion venom has been reported due to the
presence of recombinant peptides. rBmalphaTX14 is an alpha-neurotoxin extracted
from the venom gland of the East Asian scorpion Buthus martensii Karsch and can
affect ion channel conductance. Here, we investigated the functions of
rBmalphaTX14 using the Caenorhabditis elegans model. Using western blot analysis,
rBmalphaTX14 was shown to be expressed both in the cytoplasm and inclusion bodies
in the E.coli Rosetta (DE3) strain. Circular dichroism spectroscopy analysis
demonstrated that purified rBmalphaTX14 retained its biological structures. Next,
feeding nematodes with E.coli Rosetta (DE3) expressing rBmalphaTX14 caused
extension of the life span and promoted the locomotion of the nematodes. In
addition, we identified several genes that play various roles in the life span
and locomotion of C. elegans through microarray analysis and quantitative real
time PCR. Furthermore, if the amino acid site H15 of rBmalphaTX14 was mutated,
rBmalphaTX14 no longer promoted the C. elegans life span. In conclusion, the
results not only demonstrated the functions and mechanism of rBmalphaTX14 in C.
elegans, but also provided the new sight in the utility of recombinant peptides
from scorpion venom.
PMID- 27611315
TI - Genetically Determined Response to Artemisinin Treatment in Western Kenyan
Plasmodium falciparum Parasites.
AB - Genetically determined artemisinin resistance in Plasmodium falciparum has been
described in Southeast Asia. The relevance of recently described Kelch 13
propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is
still unknown. Southeast Asia parasites have low genetic diversity compared to
Sub-Saharan Africa, where parasites are highly genetically diverse. This study
attempted to elucidate whether genetics provides a basis for discovering
molecular markers in response to artemisinin drug treatment in P. falciparum in
Kenya. The genetic diversity of parasites collected pre- and post- introduction
of artemisinin combination therapy (ACT) in western Kenya was determined. A panel
of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed
across the P. falciparum genome were genotyped. Parasite clearance rates were
obtained for the post-ACT parasites. The 12 microsatellites were highly
polymorphic with post-ACT parasites being significantly more diverse compared to
pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post
ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single
clone infections. Analysis revealed 3 SNPs that might have some causal
association with parasite clearance rates. Further, genetic analysis using
Bayesian tree revealed parasites with similar clearance phenotypes were more
closely genetically related. With further studies, SNPs described here and
genetically determined response to artemisinin treatment might be useful in
tracking artemisinin resistance in Kenya.
PMID- 27611317
TI - Global Regulatory T-Cell Research from 2000 to 2015: A Bibliometric Analysis.
AB - We aimed to analyze the global scientific output of regulatory T-cell (Treg)
research and built a model to qualitatively and quantitatively evaluate
publications from 2000 to 2015. Data were obtained from the Web of Science Core
Collection (WoSCC) of Thomson Reuters on January 1, 2016. The bibliometric method
and Citespace III were used to analyze authors, journals, publication outputs,
institutions, countries, research areas, research hotspots, and trends. In total,
we identified 35,741 publications on Treg research from 2000 to 2015, and
observed that the annual publication rate increased with time. The Journal of
Immunology published the highest number of articles, the leading country was the
USA, and the leading institute was Harvard University. Sakaguchi, Hori, Fontenot,
and Wang were the top authors in Treg research. Immunology accounted for the
highest number of publications, followed by oncology, experimental medicine, cell
biology, and hematology. Keyword analysis indicated that autoimmunity,
inflammation, cytokine, gene expression, foxp3, and immunotherapy were the
research hotspots, whereas autoimmune inflammation, gene therapy, granzyme B,
RORgammat, and th17 were the frontiers of Treg research. This bibliometric
analysis revealed that Treg-related studies are still research hotspots, and that
Treg-related clinical therapies are the research frontiers; however, further
study and collaborations are needed worldwide. Overall, our findings provide
valuable information for the editors of immunology journals to identify new
perspectives and shape future research directions.
PMID- 27611319
TI - Counseling Women and Couples on Family Planning: A Randomized Study in Jordan.
AB - This article evaluates the effects of involving men in family planning counseling
in Jordan using a randomized experiment. We randomly assigned a sample of 1,247
married women to receive women-only counseling, couples counseling, or no
counseling. We measured the effects of each type of counseling on family planning
use, knowledge, attitudes, and spousal communication about family planning.
Compared to no counseling, couples counseling led to a 54 percent increase in
uptake of modern methods. This effect is not significantly different from the 46
percent increase in modern method uptake as a result of women-only counseling.
This outcome may be due, in part, to lower rates of compliance with the
intervention among those assigned to couples counseling compared to women-only
counseling. To realize the possible added benefits of involving men, more
tailored approaches may be needed to increase men's participation.
PMID- 27611320
TI - Bangladesh 2014.
PMID- 27611321
TI - Kenya 2014.
PMID- 27611318
TI - Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower
Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal
Keratinocytes.
AB - Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane
pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP).
These damages are the major cause of skin cancer because in turn, they can lead
to signature UV mutations. The eye is exposed to UV light, but the cornea is
orders of magnitude less prone to UV-induced cancer. In an attempt to shed light
on this paradox, we compared cells of the corneal epithelium and the epidermis
for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found
similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and
lower UV-induced apoptosis sensitivity in corneal epithelial cells than
epidermal. We then investigated levels of DDB2, a UV-induced DNA damage
recognition protein mostly impacting CPD repair, XPC, essential for the repair of
both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response.
We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal
cells. According to our results analyzing the protein stability of DDB2 and XPC,
the higher level of DDB2 and XPC in corneal epithelial cells is most likely due
to an increased stability of the protein. Taken together, our results show that
corneal epithelial cells have a better efficiency to repair UV-induced mutagenic
CPD. On the other hand, they are less prone to UV-induced apoptosis, which could
be related to the fact that since the repair is more efficient in the HCEC, the
need to eliminate highly damaged cells by apoptosis is reduced.
PMID- 27611323
TI - Ear Aesthetics: Investigation by the Use of an Online Viral Survey.
AB - INTRODUCTION: The ear is a key facial feature and yet few studies have previously
assessed ear aesthetics. This study aimed to assess the anatomical components of
the ear that have the greatest impact on the perception of ear aesthetics.
MATERIALS AND METHODS: Three photographs of a male adult ear (close-up, lateral,
posterior) were digitally manipulated such that in each, 1 anatomical element of
the ear was either enlarged or reduced. A complete set of 16 photographs
including a repeat of the original ear as a control were randomized and entered
into an online survey that required respondents to rate the attractiveness of
each ear on a scale of 1 (least attractive) to 10 (most attractive). The survey
was disseminated using email and social media. RESULTS: A total of 248 responses
were received, 155 women and 92 men. Respondents were grouped by demographics of
age and occupation. Reducing (R) or enlarging (E) the helix (R, P = 0.0256; E, P
= 0.003), concha (R, P = 0.0002; E, P = <0.0001) and lobule (R, P = 0.0006; E, P
< 0.0001) had a significant effect on ratings of attractiveness. Altering the
tragus had no significant effect (R, P = 0.448; E, P = 0.201). In lateral view,
raising the height of the ear had a significant effect (P = <0.0001) but not in
lowering the height (P = 0.3038). Increasing and decreasing the projection of the
ears both had a significant effect (P < 0.0001). CONCLUSIONS: The results of this
study have provided useful evidence regarding the anatomical components of the
ear that have the greatest effect on ear aesthetics. Furthermore, this study has
proven the usefulness of conducting research using viral online surveys.
PMID- 27611322
TI - Sputum Leucine-Rich Alpha-2 Glycoprotein as a Marker of Airway Inflammation in
Asthma.
AB - BACKGROUND: Asthma is a chronic inflammatory disease of airways, but an ideal
biomarker that accurately reflects ongoing airway inflammation has not yet been
established. The aim of this study was to examine the potential of sputum leucine
rich alpha-2 glycoprotein (LRG) as a new biomarker for airway inflammation in
asthma. METHODS: We obtained induced sputum samples from patients with asthma (N
= 64) and healthy volunteers (N = 22) and measured LRG concentration by sandwich
enzyme-linked immunosorbent assay (ELISA). Ovalbumin (OVA)-induced asthma model
mice were used to investigate the mechanism of LRG production during airway
inflammation. The LRG concentrations in the bronchoalveolar lavage fluid (BALF)
obtained from mice were determined by ELISA and mouse lung sections were stained
with anti-LRG antibody and periodic acid-Schiff (PAS) reagent. RESULTS: Sputum
LRG concentrations were significantly higher in patients with asthma than in
healthy volunteers (p = 0.00686). Consistent with patients' data, BALF LRG levels
in asthma model mice were significantly higher than in control mice (p =
0.00013). Immunohistochemistry of lung sections from asthma model mice revealed
that LRG was intensely expressed in a subpopulation of bronchial epithelial
cells, which corresponded with PAS-positive mucus producing cells. CONCLUSION:
These findings suggest that sputum LRG is a promising biomarker of local
inflammation in asthma.
PMID- 27611324
TI - Mapping the Emergence of Synthetic Biology.
AB - In this paper, we apply an original scientometric analyses to a corpus comprising
synthetic biology (SynBio) publications in Thomson Reuters Web of Science to
characterize the emergence of this new scientific field. Three results were drawn
from this empirical investigation. First, despite the exponential growth of
publications, the study of population level statistics (newcomers proportion,
collaboration network structure) shows that SynBio has entered a stabilization
process since 2010. Second, the mapping of textual and citational networks shows
that SynBio is characterized by high heterogeneity and four different approaches:
the central approach, where biobrick engineering is the most widespread; genome
engineering; protocell creation; and metabolic engineering. We suggest that
synthetic biology acts as an umbrella term allowing for the mobilization of
resources, and also serves to relate scientific content and promises of
applications. Third, we observed a strong intertwinement between epistemic and
socio-economic dynamics. Measuring scientific production and impact and using
structural analysis data, we identified a core set of mostly American scientists.
Biographical analysis shows that these central and influential scientists act as
"boundary spanners," meaning that their importance to the field lies not only in
their academic contributions, but also in their capacity to interact with other
social spaces that are outside the academic sphere.
PMID- 27611325
TI - Spatial and Temporal Dynamics and Value of Nature-Based Recreation, Estimated via
Social Media.
AB - Conserved lands provide multiple ecosystem services, including opportunities for
nature-based recreation. Managing this service requires understanding the
landscape attributes underpinning its provision, and how changes in land
management affect its contribution to human wellbeing over time. However,
evidence from both spatially explicit and temporally dynamic analyses is scarce,
often due to data limitations. In this study, we investigated nature-based
recreation within conserved lands in Vermont, USA. We used geotagged photographs
uploaded to the photo-sharing website Flickr to quantify visits by in-state and
out-of-state visitors, and we multiplied visits by mean trip expenditures to show
that conserved lands contributed US $1.8 billion (US $0.18-20.2 at 95%
confidence) to Vermont's tourism industry between 2007 and 2014. We found eight
landscape attributes explained the pattern of visits to conserved lands; visits
were higher in larger conserved lands, with less forest cover, greater trail
density and more opportunities for snow sports. Some of these attributes differed
from those found in other locations, but all aligned with our understanding of
recreation in Vermont. We also found that using temporally static models to
inform conservation decisions may have perverse outcomes for nature-based
recreation. For example, static models suggest conserved land with less forest
cover receive more visits, but temporally dynamic models suggest clearing forests
decreases, rather than increases, visits to these sites. Our results illustrate
the importance of understanding both the spatial and temporal dynamics of
ecosystem services for conservation decision-making.
PMID- 27611326
TI - Human Contamination in Public Genome Assemblies.
AB - Contamination in genome assembly can lead to wrong or confusing results when
using such genome as reference in sequence comparison. Although bacterial
contamination is well known, the problem of human-originated contamination
received little attention. In this study we surveyed 45,735 available genome
assemblies for evidence of human contamination. We used lineage specificity to
distinguish between contamination and conservation. We found that 154 genome
assemblies contain fragments that with high confidence originate as contamination
from human DNA. Majority of contaminating human sequences were present in the
reference human genome assembly for over a decade. We recommend that existing
contaminated genomes should be revised to remove contaminated sequence, and that
new assemblies should be thoroughly checked for presence of human DNA before
submitting them to public databases.
PMID- 27611327
TI - Route for the Generation of Trifluoromethyl-Substituted Pyrrplo[3,2-c]quinolines.
AB - Generation of trifluoromethyl-substituted pyrrolo[3,2-c]quinolines via a
copper(II)-catalyzed tandem reaction of N-(sigma-iodoaryl)alkynylimines with 2
isocyanoacetates is reported. The process involves a [3 + 2] cycloaddition and
intramolecular C-C bond coupling, leading to the fluorine-containing N
heterocycles under mild conditions with high efficiency.
PMID- 27611329
TI - Psychological autopsy of seventy high school suicides: Combined
qualitative/quantitative approach.
AB - OBJECTIVE: Suicide is the leading cause of death among Israeli youths but data on
causes are scarce. This study used psychological autopsies of 70 Israeli school
students who committed suicide during 2004-2011, attempting to determine the
causes. METHODS: Four narratives of the self were identified (qualitative
analysis) and compared (quantitative analysis): (1) regressive: functioning and
mood deteriorated continuously (45%); (2) tragic: doing well until rapid decline
around suicidal crisis (20%); (3) unstable: peaks and crises throughout life
(20%); and (4) stable: long lasting state of adverse living circumstances (15%).
Functioning, mental disorders, stressful life events and substance abuse were
examined. RESULTS: A representative profile of the suicide-completer emerged.
Suicidality in the tragic narrative involved shorter crisis, fewer risk factors
and less psychopathology than the other narratives, also better general
functioning and better school performance. Though decrease in functioning was
evident in all groups, in the tragic group it tended to be disregarded.
CONCLUSION: This study presents an in-depth analysis of a unique suicide
population of high school students. A combined methodology of qualitative and
quantitative analyses reveals a distinct subpopulation of suicidal adolescents
with little or no overt psychopathology that poses a challenge to suicide
prevention strategies.
PMID- 27611328
TI - Stimulation-Based Control of Dynamic Brain Networks.
AB - The ability to modulate brain states using targeted stimulation is increasingly
being employed to treat neurological disorders and to enhance human performance.
Despite the growing interest in brain stimulation as a form of neuromodulation,
much remains unknown about the network-level impact of these focal perturbations.
To study the system wide impact of regional stimulation, we employ a data-driven
computational model of nonlinear brain dynamics to systematically explore the
effects of targeted stimulation. Validating predictions from network control
theory, we uncover the relationship between regional controllability and the
focal versus global impact of stimulation, and we relate these findings to
differences in the underlying network architecture. Finally, by mapping brain
regions to cognitive systems, we observe that the default mode system imparts
large global change despite being highly constrained by structural connectivity.
This work forms an important step towards the development of personalized
stimulation protocols for medical treatment or performance enhancement.
PMID- 27611330
TI - Novel psychoactive substances: An investigation of temporal trends in social
media and electronic health records.
AB - BACKGROUND: Public health monitoring is commonly undertaken in social media but
has never been combined with data analysis from electronic health records. This
study aimed to investigate the relationship between the emergence of novel
psychoactive substances (NPS) in social media and their appearance in a large
mental health database. METHODS: Insufficient numbers of mentions of other NPS in
case records meant that the study focused on mephedrone. Data were extracted on
the number of mephedrone (i) references in the clinical record at the South
London and Maudsley NHS Trust, London, UK, (ii) mentions in Twitter, (iii)
related searches in Google and (iv) visits in Wikipedia. The characteristics of
current mephedrone users in the clinical record were also established. RESULTS:
Increased activity related to mephedrone searches in Google and visits in
Wikipedia preceded a peak in mephedrone-related references in the clinical record
followed by a spike in the other 3 data sources in early 2010, when mephedrone
was assigned a 'class B' status. Features of current mephedrone users widely
matched those from community studies. CONCLUSIONS: Combined analysis of
information from social media and data from mental health records may assist
public health and clinical surveillance for certain substance-related events of
interest. There exists potential for early warning systems for health-care
practitioners.
PMID- 27611331
TI - Big Five personality traits and medically unexplained symptoms in later life.
AB - BACKGROUND: Personality dysfunction has been postulated as the most clinically
salient problem of persons suffering from medically unexplained symptoms (MUS)
but empirical studies are scarce. This study aims to compare the personality
profile of older patients suffering from MUS with two comparison groups and a
control group. METHODS: Ninety-six older patients with MUS were compared with 153
frequent attenders in primary care suffering from medically explained symptoms
(MES), 255 patients with a past-month depressive disorder (DSM-IV-TR), and a
control group of 125 older persons. The Big Five personality domains (NEO-Five
Factor Inventory) were compared between groups by multiple ANCOVAs adjusted for
age, sex, education, partner status and cognitive functioning. Linear regression
analyses were applied to examine the association between health anxiety (Whitley
Index) and somatization (Brief Symptom Inventory). RESULTS: The four groups
differed with respect to neuroticism (P<0.001), extraversion (P<0.001), and
agreeableness (P=0.045). Post hoc analyses, showed that MUS patients compared to
controls scored higher on neuroticism and agreeableness, and compared to
depressed patients lower on neuroticism and higher on extraversion as well
agreeableness. Interestingly, MUS and MES patients had a similar personality
profile. Health anxiety and somatization were associated with a higher level of
neuroticism and a lower level of extraversion and conscientiousness, irrespective
whether the physical symptom was explained or not. CONCLUSIONS: Older patients
with MUS have a specific personality profile, comparable to MES patients. Health
anxiety and somatization may be better indicators of psychopathology than whether
a physical symptom is medically explained or not.
PMID- 27611332
TI - Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A
Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in
Mice.
AB - Group A Streptococcus (GAS) causes diverse infections ranging from common
pharyngitis to rare severe invasive infections. Invasive GAS isolates can have
natural mutations in the virulence regulator CovRS, which result in enhanced
expression of multiple virulence genes, suppressed the expression of the protease
SpeB, and increased virulence. It is believed that CovRS mutations arise during
human infections with GAS carrying wild-type CovRS and are not transmissible.
CovRS mutants of invasive GAS of the emm1 genotype arise readily during
experimental infection in mice. It is possible that invasive GAS arises from
pharyngeal GAS through rare genetic mutations that confer the capacity of mutated
GAS to acquire covRS mutations during infection. The objective of this study was
to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced
propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and
whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The
propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28
SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined
during subcutaneous infection of mice. The majority of both invasive and
pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and
emm28 isolates, were found to acquire SpeBA- variants during skin infection in
mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection
acquired covRS mutations and produced more platelet-activating factor
acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates
and emm12 GAS have a similar capacity to acquire covRS mutations in vivo. The
rarity of severe invasive infections caused by GAS does not appear to be
attributable to a reduced ability of pharyngeal isolates to acquire CovRS
mutations.
PMID- 27611333
TI - Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in
Mastocytosis.
AB - Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates
with activating mutations in the receptor tyrosine kinase KIT. Constitutive
activation of tyrosine kinase oncogenes has been linked to imbalances in
oxidant/antioxidant mechanisms in other myeloproliferative disorders. However,
the impact of KIT mutations on the redox status in SM and the potential
therapeutic implications are not well understood. Here, we examined the
regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1
(PARK-7), which increases with cancer progression and acts to lessen oxidative
damage to malignant cells, in relationship with SM severity. ROS levels were
increased in both indolent (ISM) and aggressive variants of the disease (ASM).
However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they
rose in ISM with higher mast cell burden and were significantly elevated in
patients with ASM. Studies on mast cell lines revealed that activating KIT
mutations induced constant ROS production and consequent DJ-1 oxidation and
degradation that could explain the reduced levels of DJ-1 in the ISM population,
while IL-6, a cytokine that increases with disease severity, caused a
counteracting transcriptional induction of DJ-1 which would protect malignant
mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the
biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast
cells accumulate, findings which were reversed with anti-IL-6 receptor blocking
antibody. Our findings provide evidence of increased ROS and a biphasic
regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1
induction and expansion of mast cells with KIT mutations. We propose
consideration of IL-6 blockade as a potential adjunctive therapy in the treatment
of patients with advanced mastocytosis, as it would reduce DJ-1 levels making
mutation-positive mast cells vulnerable to oxidative damage.
PMID- 27611334
TI - Age-Related Uptake of Heavy Metals in Human Spinal Interneurons.
AB - Toxic heavy metals have been implicated in the loss of spinal motoneurons in
amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Motoneuron loss in
the spinal anterior horn is severe in ALS/MND at the time of death, making this
tissue unsuitable for examination. We therefore examined spinal cords of people
without muscle weakness to look for any presence of heavy metals that could make
these neurons susceptible to damage. Spinal cord samples from 50 individuals aged
1-95 y who had no clinical or histopathological evidence of spinal motoneuron
loss were studied. Seven MUm formalin-fixed paraffin-embedded sections were
stained for heavy metals with silver nitrate autometallography (AMGHM) which
detects intracellular mercury, silver or bismuth. Neurons in the spinal cord were
classified as interneurons or alpha-motoneurons based on their site and cell body
diameter. Spinal interneurons containing heavy metals were present in 8 of 24
people (33%) aged 61-95 y, but not at younger ages. These AMGHM interneurons were
most numerous in the lumbar spinal cord, with moderate numbers in the caudal
cervical cord, few in the rostral cervical cord, and almost none in the thoracic
cord. All people with AMGHM interneurons had occasional AMGHM staining in alpha
motoneurons as well. In one man AMGHM staining was present in addition in
dorsomedial nucleus and sensory neurons. In conclusion, heavy metals are present
in many spinal interneurons, and in a few alpha-motoneurons, in a large
proportion of older people. Damage to inhibitory interneurons from toxic metals
in later life could result in excitotoxic injury to motoneurons and may underlie
motoneuron injury or loss in conditions such as ALS/MND, multiple sclerosis,
sarcopenia and calf fasciculations.
PMID- 27611335
TI - Stress Increases Gonadotropin Inhibitory Hormone Cell Activity and Input to GnRH
Cells in Ewes.
AB - Stress reduces GnRH and gonadotropin secretion in sheep, but the central
mechanism for this suppressive effect is unknown. Gonadotropin-inhibitory hormone
(GnIH) negatively regulates GnRH neurons and gonadotropes. Here, we measured
activity of GnIH neurons and contact of GnIH fibers on GnRH neurons during either
chronic "pseudostress" or acute stress in sheep. We also measured GnIH secretion
into hypophysial portal blood during pseudostress and acute stress. The
pseudostress was daily im injections (0.5 mg) of Synacthen Depot
(adrenocorticotropin) or vehicle for 4 weeks, which increased the GnIH cell
number and gene expression/cell in the hypothalamus, measured by in situ
hybridization. Double label immunohistochemistry showed that Synacthen Depot
treatment increased the percentage of GnRH cells in close contact with GnIH
fibers but did not alter GnIH levels in hypophysial portal blood. Acute stress
protocols were either sequential audiovisual predator stress, followed by insulin
induced hypoglycemia, or a single challenge with lipopolysaccharide (iv). Both of
these acute stressors activated a c-Fos response in GnIH cells and increased the
contacts of GnIH fibers to GnRH cells. Neither acute stress protocol increased
GnIH secretion into hypophysial portal blood. These data show that chronic
pseudostress and acute stressors increase the function of GnIH cells as well as
the degree to which GnIH cells may provide input to GnRH cells. Thus, GnIH cells
may provide a central mechanism whereby stress compromises reproduction. Neither
chronic pseudostress nor acute stress elevates secretion of GnIH into portal
blood, but stress effects mediated by GnIH cells are directed towards GnRH cell
bodies.
PMID- 27611337
TI - Novel technology for liver regeneration and replacement.
PMID- 27611338
TI - Influence of Sinus Floor Configuration on Grafted Bone Remodeling After Osteotome
Sinus Floor Elevation.
AB - BACKGROUND: This study investigates influence of the sinus floor configuration on
dimensional stability of grafted bone height after the osteotome sinus grafting
procedure. METHODS: Forty single-tooth dental implants inserted after placement
of bioglass and/or allograft into the sinus area using an osteotome technique in
37 patients were evaluated in this retrospective study. Periapical radiographs
were taken using the long-cone technique before and after implant placement.
Specifically, radiographic measurements of grafted bone height at the mesial and
distal side of each implant were taken, and the sinus floor configuration was
classified into concave, angle, and flat according to the sinus floor profile at
the implant site. Furthermore, the intruding angle, defined as the angle between
the implant axis and sinus floor, was measured. RESULTS: All implants were
clinically stable during a mean follow-up period of 39.2 months. Mean initial
gain of sinus grafted bone height was 7.0 +/- 1.9 mm, and later it was reduced to
4.6 +/- 1.9 mm at follow-up (P <0.001). A greater reduction in grafted bone
height was revealed in the flat sinus group compared with the concave group (P
<0.001). Results from the linear regression showed larger intruding angles were
statistically significantly associated with a greater reduction in grafted bone
height (r2 = 0.55, P <0.001). CONCLUSION: All bioglass and/or allograft placed in
the maxillary sinus after the osteotome technique underwent remodeling and
shrinkage; however, the outcome of the procedure was more predictable in sinuses
with a concave floor and small implant-intruding angles.
PMID- 27611339
TI - Obesity and Periodontal Outcomes: A Population-Based Cohort Study in Brazil.
AB - BACKGROUND: The aim of this study is to investigate the effects of abdominal and
general obesity on periodontal outcomes in a population-based cohort of Brazilian
adults. METHODS: Abdominal and general obesity were assessed in the years 2009 (n
= 1,720) and 2012 (n = 1,222). For abdominal obesity, a dichotomous variable was
created: 1) eutrophic/lost weight or 2) obese/gained weight. For general obesity,
a categorical variable was created: 1) eutrophic/lost weight; 2) gained weight;
or 3) obese. Periodontal outcomes were percentage of teeth with bleeding on
probing (BOP) and combination of BOP and attachment loss (AL). Hypertension was
set as the mediator. Marginal structural models (MSMs) were used to estimate the
controlled direct effect of obesity on periodontal outcomes. RESULTS: Periodontal
data were presented from 1,066 participants. The total effect model showed those
with general obesity in the cohort period presented higher risk of unfavorable
periodontal outcomes (rate ratio [RR]: 1.45 for AL and BOP in different teeth;
RR: 1.84 for AL and BOP in the same tooth). Estimates from MSMs revealed an
effect of general obesity on AL and BOP in different teeth (RR: 1.44). No effect
of general obesity was noted on the percentage of BOP. Total effect of abdominal
obesity increased risk of AL and BOP in different teeth (RR: 1.47), AL and BOP in
the same tooth (RR: 2.77), and percentage of BOP (RR: 1.49). In a MSM, those with
abdominal obesity presented greater risk of AL and BOP in the same tooth (RR:
2.16) and percentage of BOP (RR: 1.37). CONCLUSION: Abdominal obesity has a
direct effect on unfavorable periodontal outcomes in MSMs.
PMID- 27611340
TI - Air Quality Impact of Diffuse and Inefficient Combustion Emissions in Africa
(DICE-Africa).
AB - Anthropogenic pollution in Africa is dominated by diffuse and inefficient
combustion sources, as electricity access is low and motorcycles and outdated
cars proliferate. These sources are missing, out-of-date, or misrepresented in
state-of-the-science emission inventories. We address these deficiencies with a
detailed inventory of Diffuse and Inefficient Combustion Emissions in Africa
(DICE-Africa) for 2006 and 2013. Fuelwood for energy is the largest emission
source in DICE-Africa, but grows from 2006 to 2013 at a slower rate than charcoal
production and use, and gasoline and diesel for motorcycles, cars, and
generators. Only kerosene use and gas flaring decline. Increase in emissions from
2006 to 2013 in this work is consistent with trends in satellite observations of
formaldehyde and NO2, but much slower than the explosive growth projected with a
fuel consumption model. Seasonal biomass burning is considered a large pollution
source in Africa, but we estimate comparable emissions of black carbon and higher
emissions of nonmethane volatile organic compounds from DICE-Africa. Nitrogen
oxide (NOx = NO + NO2) emissions are much lower than from biomass burning. We use
GEOS-Chem to estimate that the largest contribution of DICE-Africa to annual mean
surface fine particulate matter (PM2.5) is >5 MUg m-3 in populous Nigeria.
PMID- 27611336
TI - TGFbeta Superfamily Members Mediate Androgen Deprivation Therapy-Induced Obese
Frailty in Male Mice.
AB - First line treatment for recurrent and metastatic prostate cancer is androgen
deprivation therapy (ADT). Use of ADT has been increasing in frequency and
duration, such that side effects increasingly impact patient quality of life. One
of the most significant side effects of ADT is sarcopenia, which leads to a loss
of skeletal muscle mass and function, resulting in a clinical disability syndrome
known as obese frailty. Using aged mice, we developed a mouse model of ADT
induced sarcopenia that closely resembles the phenotype seen in patients,
including loss of skeletal muscle strength, reduced lean muscle mass, and
increased adipose tissue. Sarcopenia onset occurred about 6 weeks after
castration and was blocked by a soluble receptor (ActRIIB-Fc) that binds multiple
TGFbeta superfamily members, including myostatin, growth differentiation factor
11, activin A, activin B, and activin AB. Analysis of ligand expression in both
gastrocnemius and triceps brachii muscles demonstrates that each of these
proteins is induced in response to ADT, in 1 of 3 temporal patterns.
Specifically, activin A and activin AB levels increase and decline before onset
of strength loss at 6 weeks after castration, and myostatin levels increase
coincident with the onset of strength loss and then decline. In contrast, activin
B and growth differentiation factor 11 levels increase after the onset of
strength loss, 8-10 weeks after castration. The observed patterns of ligand
induction may represent differential contributions to the development and/or
maintenance of sarcopenia. We hypothesize that some or all of these ligands are
targets for therapy to ameliorate ADT-induced sarcopenia in prostate cancer
patients.
PMID- 27611341
TI - Effect of total contact cast in non-healing diabetic foot ulcers in Lebanese
patients.
AB - The aim of this study was to evaluate the effectiveness of total contact casting
(TCC) in treating non-healing diabetic foot ulcers in Lebanese diabetic patients.
Twenty-three diabetic patients were treated with TCC, and relevant data were
collected retrospectively. Sixteen patients were analysed; the average duration
of casting was 6 weeks, and 75% of the patients achieved complete ulcer closure
without recurrence during one year of follow-up and without any complications.
TCC appears to be an effective treatment of diabetic foot ulcers.
PMID- 27611342
TI - Exploring the contributions of the supplementary eye field to subliminal
inhibition using double-pulse transcranial magnetic stimulation.
AB - It is widely accepted that the supplementary eye fields (SEF) are involved in the
control of voluntary eye movements. However, recent evidence suggests that SEF
may also be important for unconscious and involuntary motor processes. Indeed,
Sumner et al. ([2007]: Neuron 54:697-711) showed that patients with micro-lesions
of the SEF demonstrated an absence of subliminal inhibition as evoked by masked
prime stimuli. Here, we used double-pulse transcranial magnetic stimulation (TMS)
in healthy volunteers to investigate the role of SEF in subliminal priming. We
applied double-pulse TMS at two time windows in a masked-prime task: the first
during an early phase, 20-70 ms after the onset of the mask but before target
presentation, during which subliminal inhibition is present; and the second
during a late phase, 20-70 ms after target onset, during which the saccade is
being prepared. We found no effect of TMS with the early time window of
stimulation, whereas a reduction in the benefit of an incompatible subliminal
prime stimulus was found when SEF TMS was applied at the late time window. These
findings suggest that there is a role for SEF related to the effects of
subliminal primes on eye movements, but the results do not support a role in
inhibiting the primed tendency. Hum Brain Mapp 38:339-351, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27611343
TI - Online sample concentration and analysis of drugs of abuse in human urine by
micelle to solvent stacking in capillary zone electrophoresis.
AB - A sensitive and rapid CZE-UV method was developed to determine drugs and their
metabolites' presence in human urine. Ten drugs of abuse were analyzed including
four amphetamines, cocaine, cocaethylene, heroin, morphine, 6-monoacetylmorphine,
and 4-methylmethcathinone. An MSS (micelle to solvent stacking) approach was
evaluated to enhance method sensitivity. This method considers composition of the
micellar sample solution matrix and the injection time. Several analytical
conditions influencing the resolution of the drugs mixture as pH and buffer
concentration, organic solvent content, were also investigated. The base-line
separation of all studied analytes in the same run was achieved within 18 min in
an uncoated fused silica capillary (50 MUm id * 60 cm) using a background
solution containing 50 mM phosphate buffer pH 2.5 and 30% ACN v/v. Other
experimental parameters such as applied voltage and capillary temperature were
set up at 20 kV and 20 degrees C, respectively. LOD values ranging between 15 and
75 ng/mL for all studied compounds were obtained. From a comparison with
conventional CZE, the proposed method provides an increase of sensitivity (39- to
55-fold enhancement factor). Under optimal MSS-CZE conditions, good linearity was
achieved (R2 <= 0.9998). The method was finally applied to the analysis of urine
samples spiked with a standard mixture after a sample pretreatment, reaching
satisfactory recovery values.
PMID- 27611344
TI - Daughters of the Enamel Organ: Development, Fate, and Function of the Stratum
Intermedium, Stellate Reticulum, and Outer Enamel Epithelium.
AB - The tooth enamel organ (EO) is a complex epithelial cell assembly involved in
multiple aspects of tooth development, including amelogenesis. The present study
focuses on the role of the nonameloblast layers of the EO, the stratum
intermedium, the stellate reticulum, and the outer enamel epithelium (OEE). The
secretory stage stratum intermedium was distinguished by p63-positive epithelial
stem cell marks, highly specific alkaline phosphatase labeling, as well as
multiple desmosomes and gap junctions. At the location of the presecretory stage
stellate reticulum, the pre-eruption EO prominently featured the papillary layer
(PL) as a keratin immunopositive network of epithelial strands between tooth
crowns and oral epithelium. PL cell strands contained numerous p63-positive
epithelial stem cells, while BrdU proliferative cells were detected at the outer
boundaries of the PL, suggesting that the stellate reticulum/PL epithelial cell
sheath proliferated to facilitate an epithelial seal during tooth eruption.
Comparative histology studies demonstrated continuity between the OEE and the
general lamina of continuous tooth replacement in reptiles, and the outer layer
of Hertwig's epithelial root sheath in humans, implicating the OEE as the
formative layer for continuous tooth replacement and tooth root extension. Cell
fate studies in organ culture verified that the cervical portion of the mouse
molar EO gave rise to Malassez rest-like cell islands. Together, these studies
indicate that the nonameloblast layers of the EO play multiple roles during
odontogenesis, including the maintenance of several p63-positive stem cell
reservoirs, a role during tooth root morphogenesis and tooth succession, a
stabilizing function for the ameloblast layer, the facilitation of ion transport
from the EO capillaries to the enamel layer, as well as safe and seamless tooth
eruption.
PMID- 27611345
TI - Elevated exhalation of hydrogen peroxide in patients with non-small cell lung
cancer is not affected by chemotherapy.
AB - OBJECTIVES: Reactive oxygen species, which are implicated in the process of
carcinogenesis, are also responsible for cell death during chemotherapy (CHT).
Therefore, the aim of the study was to evaluate exhaled H2O2 levels in non-small
cell lung cancer (NSCLC) patients before and after CHT. METHODS: Thirty patients
(age 61.3 +/- 9.3 years) with advanced NSCLC (stage IIIB-IV) and 15 age-matched
healthy cigarette smokers were enrolled into the study. Patients received four
cycles of cisplatin or carboplatin with vinorelbine every three weeks. Before and
after the first, second, and fourth cycle, the concentration of H2O2 in exhaled
breath condensate was measured with respect to treatment response. RESULTS: At
the baseline, NSCLC patients exhaled 3.8 times more H2O2 than the control group
(0.49 +/- 0.14 vs. 0.13 +/- 0.03 umol/L, P < 0.05); this difference persisted
throughout the study. CHT had no noticeable effect on exhaled H2O2 levels
independent of the treatment response (partial remission vs. progressive
disease). Pre- and post-CHT cycles of H2O2 levels generally correlated
positively. DISCUSSION: The study demonstrated the occurrence of oxidative stress
in the airways of advanced NSCLC patients. Exhaled H2O2 level was not affected by
CHT and independent of treatment results and changes in the number of circulating
neutrophils.
PMID- 27611347
TI - Controlling the motion of multiple objects on a Chladni plate.
AB - The origin of the idea of moving objects by acoustic vibration can be traced back
to 1787, when Ernst Chladni reported the first detailed studies on the
aggregation of sand onto nodal lines of a vibrating plate. Since then and to this
date, the prevailing view has been that the particle motion out of nodal lines is
random, implying uncontrollability. But how random really is the out-of-nodal
lines motion on a Chladni plate? Here we show that the motion is sufficiently
regular to be statistically modelled, predicted and controlled. By playing
carefully selected musical notes, we can control the position of multiple objects
simultaneously and independently using a single acoustic actuator. Our method
allows independent trajectory following, pattern transformation and sorting of
multiple miniature objects in a wide range of materials, including electronic
components, water droplets loaded on solid carriers, plant seeds, candy balls and
metal parts.
PMID- 27611346
TI - Aerobic Fitness and Neurocognitive Function Scores in Young Faroese Adults and
Potential Modification by Prenatal Methylmercury Exposure.
AB - BACKGROUND: Exposure to methylmercury was shown to decrease neural stem cell
populations, whereas aerobic fitness has beneficial effects on the adult brain
that relies on improved neurogenesis in the hippocampus. OBJECTIVES: We examined
the association between aerobic fitness and neurocognitive outcomes at young
adult age, along with the potential moderating effect of prenatal exposure to
methylmercury. METHODS: At age 22 years, 262 members of a Faroese birth cohort,
established in 1986-1987, underwent a graded exercise test of aerobic fitness to
measure maximal oxygen uptake (VO2Max). Their prenatal methylmercury exposure had
been assessed from the mercury concentration in cord blood. We estimated cross
sectional associations between VO2Max and multiple measures of neurocognitive
function. In addition, we compared groups with low and high prenatal
methylmercury exposure. RESULTS: A 1 standard deviation (SD) increase in VO2Max
was associated with better scores on short-term memory and cognitive processing
speed by 0.21 SD (95% CI: -0.04, 0.46) and 0.28 SD (95% CI: 0.02, 0.54),
respectively. In the group with lower prenatal methylmercury exposure, a 1 SD
increase in VO2Max was associated with increased scores on cognitive processing
speed by 0.45 SD (95% CI: 0.08, 0.81) and with a slightly lesser benefit in short
term memory. No such association was observed in the group with high prenatal
methylmercury exposure. CONCLUSIONS: Higher aerobic capacity was associated with
better performance in short-term memory and processing speed. However, prenatal
methylmercury exposure seemed to attenuate these positive associations.
PMID- 27611349
TI - Attending patient funerals: Practices and attitudes of Australian medical
practitioners.
AB - The appropriateness of attending a patient's funeral is a medical dilemma. This
article focuses on 437 doctors who participated in an online survey. Seventy-one
percent of general practitioners, 67% of oncologists, 67% of psychiatrists, 63%
of palliative medicine specialists, 52% of surgeons, and 22% of intensive care
specialists had attended patient funerals. Significant differences in
demographics and between specialties were identified in terms of barriers and
benefits associated with attendance. Although attendance is a personal decision,
there is a need for open discussions in medical education and professional
development concerning death and the role of doctors after a patient dies.
PMID- 27611348
TI - Rapid 3D imaging of the lower airway by MRI in patients with congenital heart
disease: A retrospective comparison of delayed volume interpolated breath-hold
examination (VIBE) to turbo spin echo (TSE).
AB - OBJECTIVE: When imaging the lower airway by MRI, the traditional technique turbo
spin echo (TSE) results in high quality 2D images, however planning and
acquisition times are lengthy. An alternative, delayed volume interpolated breath
holds examination (VIBE), is a 3D gradient echo technique that produces high
spatial resolution imaging of the airway in one breath-hold. The objective of
this study is to retrospectively evaluate the accuracy of lower airway
measurements obtained by delayed VIBE when compared to TSE. DESIGN: Patients with
congenital heart disease who underwent a cardiac MRI (CMR) that included a
delayed VIBE sequence from 5/2008 to 9/2013 were included. Standard TSE imaging
was performed and delayed VIBE was acquired 5 min after gadolinium contrast
administration. Airway measurements were made on both sequences by two observers
in a blinded fashion to the other observer and other technique. Intraclass
correlations (ICC) were calculated to assess for agreement between both
techniques and the observers. RESULTS: 29 studies met inclusion criteria with a
mean patient age of 8.8 years (2 months to 63 years) and mean patient weight of
30.2 kg (3.5-110). All delayed VIBE and TSE sequences were found to be of
diagnostic quality. Mean acquisition time was shorter for the delayed VIBE (13.1
seconds) than TSE (949.9 seconds). Overall there was very good agreement between
the delayed VIBE and TSE measurements for both observers (ICC 0.78-0.94) with the
exception of the distal right bronchus (ICC 0.67) The interobserver agreement was
also excellent for both TSE (ICC 0.78-0.96) and VIBE (ICC 0.85-0.96). CONCLUSION:
Delayed VIBE is rapid and at least as accurate as the alternative TSE imaging for
assessment of the lower airway by MRI across a wide spectrum of patients.
PMID- 27611350
TI - Sibling Relationships in Adolescence and Early Adulthood With People Who Have
Intellectual Disability.
AB - Cross-sectional (N = 106) and longitudinal (N = 35) samples of siblings (ages 11
38) reported on closeness and conflict in their relationships with sisters and
brothers with intellectual disability. For closeness, confirmatory factor
analysis (CFA) distinguished feelings of emotional closeness from reciprocal
sharing behaviors for these siblings. Age effects and changes over time indicated
increasing emotional closeness and a general reduction in conflict from
adolescence to young adulthood, with stable reciprocal sharing. Cross
sectionally, closeness was greater when siblings were involved in caregiving, and
conflict was less when siblings no longer co-resided. Sibling constellation
features (sex, birth order, age spacing) had limited effects at this
developmental period. Findings support a combination of life-span developmental
change and enduring attachment in these sibling relationships.
PMID- 27611351
TI - Engaging Communities in Identifying Local Strategies for Expanding Integrated
Employment During and After High School.
AB - Amidst decades of attention directed toward improving employment outcomes for
people with intellectual and developmental disabilities (IDD), few efforts have
been made to engage communities in identifying local solutions for expanding
integrated employment opportunities. We examined the implementation and outcomes
of "community conversation" events held in 6 geographically and economically
diverse locales. Each event used an asset-based dialogue approach called the
World Cafe ( Brown & Isaacs, 2005 ) to solicit ideas from a broad cross-section
of community members on improving integrated employment that reflect local
priorities and possibilities. Six key themes encapsulated the 1,556 strategies
generated by the almost 400 attendees. Although considerable consistency was
found among the categories of strategies raised across events, the manner in
which those individual strategies would be implemented locally reflected the
unique accent of each community. Attendees also viewed these events as promising
and productive pathways for identifying next steps for their community. We offer
recommendations for community-level intervention efforts and suggest directions
for future research.
PMID- 27611352
TI - Type and Intensity of Negative Life Events Are Associated With Depression in
Adults With Intellectual Disabilities.
AB - This study investigated the associations between types and intensity of life
events and symptoms of depression among adults with intellectual disabilities. A
community sample (N = 593) was screened for current depression and exposure to
life events (i.e., loss, illness, change, and bullying) during the previous 12
months. Symptoms of depression were measured using the Psychopathology Checklists
for Adults With Intellectual Disabilities. Exposure to three of the four types of
life events studied (loss, illness, and bullying) and the intensity of the events
were associated with depression, particularly in the cases of loss of relatives
and bullying. Quality of care moderated the association between bullying and
depression and may buffer the adverse consequences of bullying.
PMID- 27611353
TI - Parent Beliefs About the Causes of Learning and Developmental Problems Among
Children With Autism Spectrum Disorder: Results From a National Survey.
AB - This study aimed to assess variation in parent beliefs about causes of learning
and developmental problems in U.S. children with autism spectrum disorder, using
data from a nationally representative survey. Results showed that beliefs about a
genetic/hereditary cause of learning/developmental problems were most common, but
nearly as many parents believed in exposure causes. Forty present of parents had
no definite causal beliefs. On multivariate analysis, parents who were non-White,
publicly insured or poor were more likely than other parents to endorse exposure
causes, or less likely to endorse genetic causes, compared to other parents.
Further research should assess how these beliefs modify health care quality or
services use.
PMID- 27611354
TI - The Role of Executive Function in Independent Living Skills in Female Adolescents
and Young Adults With Fragile X Syndrome.
AB - Fragile X syndrome (FXS) is associated with executive function (EF) and
independent living skills (ILS) deficits. We examined the role of childhood EF in
ILS during adolescence/early adulthood in females with FXS and two comparison
groups in the same age range (matched for IQ [IQ/Age group] and with another
genetic condition, Turner syndrome [TS group]). EF and ILS were significantly
higher for the FXS group than the IQ/Age group but did not differ from the TS
group. For the FXS group, age and EF were significant predictors of ILS during
adolescence/early adulthood, but there were no statistically significant
longitudinal associations between EF and ILS. Our findings suggest that
impairments in EF may have a significant effect on ILS in FXS.
PMID- 27611357
TI - Decrease of dissolved sulfide in sewage by powdered natural magnetite and
hematite.
AB - : Natural magnetite and hematite were explored to decrease sulfide in sewage,
compared with iron salts (FeCl3 and FeSO4). A particle size of magnetite and
hematite ranging from 45 to 60MUm was used. The results showed that 40mgL-1 of
powdered magnetite and hematite addition decreased the sulfide in sewage by
79%and 70%, respectively. The achieved decrease of sulfide production capacities
were 197.3, 210.6, 317.6 and 283.3mgSg-1Fe for magnetite, hematite, FeCl3 and
FeSO4 at the optimal dosage of 40mgL-1, respectively. Magnetite and hematite
provided a higher decrease of sulfide production since more iron ions are capable
of being released from the solid phase, not because of adsorption capacity of per
gram iron. Besides, the impact on pH and oxidation-reduction potential (ORP) of
hematite addition was negligible; while magnetite addition resulted in slight
increase of 0.3-0.5 on pH and 10-40mV on ORP. Powdered magnetite and hematite
thus appear to be suitable for sulfide decrease in sewage, for their sparing
solubility, sustained-release, long reactive time in sewage as well as cost
effectiveness, compared with iron salts. Further investigation over long time
periods under practical conditions are needed to evaluate the possible settlement
in sewers and unwanted (toxic) metal elements presenting as impurities. CAPSULE
ABSTRACT: Powdered magnetite and hematite were more cost-effective at only 30%
costs of iron salts, such as FeCl3 and FeSO4 for decreasing sulfide production in
sewage.
PMID- 27611358
TI - Combination of Cymbopogon citratus and Allium cepa essential oils increased
antibacterial activity in leafy vegetables.
AB - BACKGROUND: Cymbopogon citratus and Allium cepa essential oils (EOs) are rich in
terpenes and sulfur compounds respectively, both with antibacterial activity and
different cell targets, supporting the idea that their combination can increase
their efficacy. RESULTS: Major constituents of C. citratus were geranial and
neral, while A. cepa presented dipropyl disulfide and dipropyl trisulfide.
Cymbopogon citratus and A. cepa EOs inhibited the in vitro growth of Escherichia
coli O157:H7 (minimal inhibitory concentrations of 2.21 and 5.13 g L-1
respectively), Salmonella Choleraesuis (3.04 and 1.28 g L-1 ), Listeria
monocytogenes (1.33 and 2.56 g L-1 ) and Staphylococcus aureus (0.44 and 5.26 g L
1 ). Application of the EO combination to spinach caused a greater reduction in
E. coli (2.34 log colony-forming units (CFU) g-1 ), S. Choleraesuis (2.94 log CFU
g-1 ), L. monocytogenes (2.06 log CFU g-1 ) and S. aureus (1.37 log CFU g-1 )
compared with higher doses of individual EOs; a similar effect was observed for
romaine lettuce. Individual and combined EOs caused a reduction in flavor
acceptability level; however, no significant differences were found among odor
acceptability of control vegetables and those treated with the EO combination and
C. citratus EO. CONCLUSION: Leafy vegetables treated with the EO combination
showed higher antibacterial protection and odor acceptability compared with
individual EO treatments. (c) 2016 Society of Chemical Industry.
PMID- 27611359
TI - Crystal Dynamics in Multi-stimuli-Responsive Entangled Metal-Organic Frameworks.
AB - An understanding of solid-state crystal dynamics or flexibility in metal-organic
frameworks (MOFs) showing multiple structural changes is highly demanding for the
design of materials with potential applications in sensing and recognition.
However, entangled MOFs showing such flexible behavior pose a great challenge in
terms of extracting information on their dynamics because of their poor single
crystallinity. In this article, detailed experimental studies on a twofold
entangled MOF (f-MOF-1) are reported, which unveil its structural response toward
external stimuli such as temperature, pressure, and guest molecules. The
crystallographic study shows multiple structural changes in f-MOF-1, by which the
3 D net deforms and slides upon guest removal. Two distinct desolvated phases,
that is, f-MOF-1 a and f-MOF-1 b, could be isolated; the former is a metastable
one and transformable to the latter phase upon heating. The two phases show
different gated CO2 adsorption profiles. DFT-based calculations provide an
insight into the selective and gated adsorption behavior with CO2 of f-MOF-1 b.
The gate-opening threshold pressure of CO2 adsorption can be tuned strategically
by changing the chemical functionality of the linker from ethanylene (-CH2 -CH2
) in f-MOF-1 to an azo (-N=N-) functionality in an analogous MOF, f-MOF-2. The
modulation of functionality has an indirect influence on the gate-opening
pressure owing to the difference in inter-net interaction. The framework of f-MOF
1 is highly responsive toward CO2 gas molecules, and these results are supported
by DFT calculations.
PMID- 27611360
TI - Cardiovascular medicine in Morgagni's De sedibus: dawn of cardiovascular
pathology.
AB - The most significant cardiovascular anatomoclinical observations from Morgagni's
masterpiece De sedibus et causis morborum per anatomen indagatis (1761) are
herein reported, divided into the current taxonomy according to cardiac
structure: (a) aorta and pulmonary artery, (b) pericardium, (c) coronary
arteries, (d) myocardium, (e) endocardium, (f) congenital heart defects, and (g)
heart rhythm disorders. Morgagni's interpretations in cardiovascular pathology
were strictly related with the most advanced theories of his time, such as those
of blood circulation and iatromechanics; nevertheless, he remained close to the
empirical description of clinical and pathological anatomy phenomena with their
individual specificity. Through a systematic review of the literature, he
compared the data from his own observations and experiments with those from
physicians he considered reliable by applying the method of literature review
which is still valid nowadays.
PMID- 27611361
TI - Assessment of sex differences in bone deficits among adolescents with anorexia
nervosa.
AB - OBJECTIVE: The objective of this study was to compare sex differences in bone
deficits among adolescents with anorexia nervosa (AN) and to identify other
correlates of bone health. METHOD: Electronic medical records of all patients 9
20 years of age with a DSM-5 diagnosis of AN who were evaluated by the eating
disorders program at Stanford with dual-energy X-ray absorptiometry (DXA) between
March 1997 and February 2011 were retrospectively reviewed. Whole body bone
mineral content Z-scores and bone mineral density (BMD) Z-scores at multiple
sites were recorded using the Bone Mineral Density in Childhood Study (BMDCS)
reference data. RESULTS: A total of 25 males and 253 females with AN were
included, with median age 15 years (interquartile range [IQR] 14-17) and median
duration of illness 9 months (IQR 5-13). Using linear regression analyses, no
significant sex differences in bone deficits were found at the lumbar spine,
total hip, femoral neck, or whole body when controlling for age, %mBMI, and
duration of illness. Lower %mBMI was significantly associated with bone deficits
at all sites in adjusted models. DISCUSSION: This is the first study to evaluate
sex differences in bone health among adolescents with AN, using novel DSM-5
criteria for AN and robust BMDCS reference data. We find no significant sex
differences in bone deficits among adolescents with AN except for a higher
proportion of females with femoral neck BMD Z-scores <-1. Degree of malnutrition
was correlated with bone deficits at all sites. (c) 2016 Wiley Periodicals,
Inc.(Int J Eat Disord 2017; 50:352-358).
PMID- 27611362
TI - Microcontact printing in bioanalysis: where are we and where shall we be?
PMID- 27611363
TI - Centipede venoms as a source of drug leads.
AB - INTRODUCTION: Centipedes are one of the oldest and most successful lineages of
venomous terrestrial predators. Despite their use for centuries in traditional
medicine, centipede venoms remain poorly studied. However, recent work indicates
that centipede venoms are highly complex chemical arsenals that are rich in
disulfide-constrained peptides that have novel pharmacology and three-dimensional
structure. Areas covered: This review summarizes what is currently known about
centipede venom proteins, with a focus on disulfide-rich peptides that have novel
or unexpected pharmacology that might be useful from a therapeutic perspective.
The authors also highlight the remarkable diversity of constrained three
dimensional peptide scaffolds present in these venoms that might be useful for
bioengineering of drug leads. Expert opinion: Like most arthropod predators,
centipede venoms are rich in peptides that target neuronal ion channels and
receptors, but it is also becoming increasingly apparent that many of these
peptides have novel or unexpected pharmacological properties with potential
applications in drug discovery and development.
PMID- 27611365
TI - Differential Diagnosis of an Inflammatory Pseudotumor of the Urinary Bladder.
PMID- 27611364
TI - Genetic testing of 248 Chinese aortopathy patients using a panel assay.
AB - Inherited aortopathy, which is characterized by a high risk of fatal aortic
aneurysms/dissections, can occur secondarily to several syndromes. To identify
genetic mutations and help make a precise diagnosis, we designed a gene panel
containing 15 genes responsible for inherited aortopathy and tested 248 probands
with aortic disease or Marfan syndrome. The results showed that 92 individuals
(37.1%) tested positive for a (likely) pathogenic mutation, most of which were
FBN1 mutations. We found that patients with a FBN1 truncating or splicing
mutation were more prone to developing severe aortic disease or valvular disease.
To date, this is the largest reported cohort of Chinese patients with aortic
disease who have undergone genetic testing. Therefore, it can serve as a
considerable dataset of next generation sequencing data analysis of Chinese
population with inherited aortopathy. Additionally, according to the accumulated
data, we optimized the analysis pipeline by adding quality control steps and
lowering the false positive rate.
PMID- 27611366
TI - Ruminal expression of the NQO1, RGS5, and ACAT1 genes may be indicators of feed
efficiency in beef steers.
AB - Ruminal genes differentially expressed in crossbred beef steers from USMARC with
variation in gain and feed intake were identified in a previous study. Several of
the genes identified with expression patterns differing between animals with high
gain-low feed intake and low gain-high feed intake were evaluated in a separate,
unrelated population of Angus * Hereford beef steers from the University of
Wyoming that was classified to differ in residual feed intake (RFI). Of the 17
genes tested, two were differentially expressed by RFI class in the Angus *
Hereford animals. These genes included NAD(P)H dehydrogenase, quinone 1 (NQO1; P
= 0.0009) and regulator of G-protein signaling 5 (RGS5; P = 0.01). A third gene,
acetyl-CoA acetyltransferase 1 (ACAT1; P = 0.06), displayed a trend toward
association with RFI. These data suggest that some of the genes identified in a
previous rumen transcriptome discovery study may have utility for identifying or
selecting for animals with superior feed efficiency phenotypes across cattle
breeds and populations.
PMID- 27611368
TI - Building Ventilation as an Effective Disease Intervention Strategy in a Dense
Indoor Contact Network in an Ideal City.
AB - Emerging diseases may spread rapidly through dense and large urban contact
networks, especially they are transmitted by the airborne route, before new
vaccines can be made available. Airborne diseases may spread rapidly as people
visit different indoor environments and are in frequent contact with others. We
constructed a simple indoor contact model for an ideal city with 7 million people
and 3 million indoor spaces, and estimated the probability and duration of
contact between any two individuals during one day. To do this, we used data from
actual censuses, social behavior surveys, building surveys, and ventilation
measurements in Hong Kong to define eight population groups and seven indoor
location groups. Our indoor contact model was integrated with an existing
epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to
estimate disease spread and with the Wells-Riley equation to calculate local
infection risks, resulting in an integrated indoor transmission network model.
This model was used to estimate the probability of an infected individual
infecting others in the city and to study the disease transmission dynamics. We
predicted the infection probability of each sub-population under different
ventilation systems in each location type in the case of a hypothetical airborne
disease outbreak, which is assumed to have the same natural history and
infectiousness as smallpox. We compared the effectiveness of controlling
ventilation in each location type with other intervention strategies. We conclude
that increasing building ventilation rates using methods such as natural
ventilation in classrooms, offices, and homes is a relatively effective strategy
for airborne diseases in a large city.
PMID- 27611367
TI - Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein
in the Postfusion Conformation.
AB - Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of
bronchiolitis and pneumonia in children less than five years of age. The hMPV
fusion (F) glycoprotein is the primary target of neutralizing antibodies and is
thus a critical vaccine antigen. To facilitate structure-based vaccine design, we
stabilized the ectodomain of the hMPV F protein in the postfusion conformation
and determined its structure to a resolution of 3.3 A by X-ray crystallography.
The structure resembles an elongated cone and is very similar to the postfusion F
protein from the related human respiratory syncytial virus (hRSV). In contrast,
significant differences were apparent with the postfusion F proteins from other
paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease
virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic
sites targeted by neutralizing antibodies prompted us to test for antibody cross
reactivity. The widely used monoclonal antibody 101F, which binds to antigenic
site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize
both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross
reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross
reactivity in the polyclonal antibody responses raised in mice against the
postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F
protein did, however, elicit high titers of hMPV-neutralizing activity,
suggesting that it could serve as an effective subunit vaccine. Structural
insights from these studies should be useful for designing novel immunogens able
to induce wider cross-reactive antibody responses.
PMID- 27611369
TI - Clinical benefits of natriuretic peptides and galectin-3 are maintained in old
dyspnoeic patients.
AB - BACKGROUND: Acute dyspnoea is the leading cause of unscheduled admission of
elderly patients. Several biomarkers are used to diagnose acute heart failure
(AHF) and assess prognosis of dyspnoeic patients, but their value in elderly
patients is unclear. OBJECTIVE: To compare diagnostic and prognostic performances
of conventional and novel cardiovascular biomarkers in 2 age groups: young (<75
years old) vs. old (>=75 years old) dyspnoeic patients. DESIGN: Prospective
observational registry. SETTING: Emergency department (ED). SUBJECTS: Acutely
dyspnoeic adult patients. METHODS: Blood samples were collected at ED admission.
The diagnostic value of 4 natriuretic peptides (BNP, proBNP, NT-proBNP, MR
proANP) for AHF was tested. We also assessed the prognostic value of same
natriuretic peptides and of 3 novel cardiovascular biomarkers (galectin-3, sST2
and proenkephalin), using 1-year all-cause mortality as end-point. Diagnostic or
prognostic performances are expressed as area under the receiveroperating
characteristic curve (AUC) with 95% confidence interval. RESULTS: Two hundred one
acutely dyspnoeic patients were studied. AHF was the cause of dyspnoea in 57% of
old and 44% of young patients, respectively. All 4 natriuretic peptides performed
well in diagnosing AHF in both age groups (all AUC>0.7). BNP showed the best
diagnostic performance in both old (AUC: 0.98 [0.97-1.00]) and young (AUC 0.98
[0.95-1.00]) patients. Galectin-3 showed the best prognostic performance in both
old (AUC 0.74 [0.62-0.87]) and young patients (AUC 0.75 [0.56-0.94]).
CONCLUSIONS: BNP and galectin-3 show good clinical benefits in both oldand young
acutely dyspnoeic patients.
PMID- 27611370
TI - Seasonal variation of human sperm cells among 4,422 semen samples: A
retrospective study in Turkey.
AB - : We aimed to assess the possible presence of a seasonal pattern in three
parameters of semen analysis: sperm concentration, morphology, and motility as a
function of the time of ejaculation and sperm production (spermatogenesis) in
normal and oligozoospermic men. This retrospective study included a consecutive
series of 4,422 semen samples that were collected from patients as a part of the
basic evaluation of the infertile couples attending the Reproductive Endocrine
Outpatient Clinic of a tertiary women's hospital in Ankara, Turkey, between
January 1, 2012 and December 31, 2013. The samples were classified according to
sperm concentration: >=15 x106/mL as normozoospermic samples and 4 -14.99 x106/mL
as oligozoospermic samples and seasonal analysis of the semen samples were
carried out separately. When the data was analyzed according to the season of
semen production, there was no seasonal effect on the sperm concentration. A
gradual and consistent decrease in the rate of sperm with fast forward motility
was observed from spring to fall with a recovery noticed during the winter. The
percentage of sperms with normal morphology was found to be statistically
significantly higher in the spring samples compared with the summer samples
(p=0.001). Both normozoospermic and oligozoospermic semen samples appeared to
have better sperm parameters in spring and winter. The circannual variation of
semen parameters may be important in diagnosis and treatment desicions.
ABBREVIATIONS: WHO: World Health Organization; mRNA:messenger ribonucleic acid.
PMID- 27611371
TI - Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and
UV-Irradiated Skin by Catalase Induction.
AB - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear hormone
receptor involved in the transcriptional regulation of lipid metabolism, fatty
acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant
enzymes such as catalase, whose expression is decreased in aged human skin. Here
we investigated the expression of PPARalpha in aged and ultraviolet (UV)
irradiated skin, and whether PPARalpha activation can modulate expressions of
matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We
found that PPARalpha mRNA level was significantly decreased in intrinsically aged
and photoaged human skin as well as in UV-irradiated skin. A PPARalpha activator,
Wy14643, inhibited UV-induced increase of MMP-1 and decrease of procollagen
expression and caused marked increase in catalase expression. Furthermore,
production of reactive oxygen species (ROS) was suppressed by Wy14643 in UV
irradiated and aged dermal fibroblasts, suggesting that the PPARalpha activation
induced upregulation of catalase leads to scavenging of ROS produced due to UV
irradiation or aging. PPARalpha knockdown decreased catalase expression and
abolished the beneficial effects of Wy14643. Topical application of Wy14643 on
hairless mice restored catalase activity and prevented MMP-13 and inflammatory
responses in skin. Our findings indicate that PPARalpha activation triggers
catalase expression and ROS scavenging, thereby protecting skin from UV-induced
damage and intrinsic aging.
PMID- 27611433
TI - Lung Sounds in Children before and after Respiratory Physical Therapy for Right
Middle Lobe Atelectasis.
AB - BACKGROUND: Chest auscultation is commonly performed during respiratory physical
therapy (RPT). However, the changes in breath sounds in children with atelectasis
have not been previously reported. The aim of this study was to clarify the
characteristics of breath sounds in children with atelectasis using acoustic
measurements. METHOD: The subjects of this study were 13 children with right
middle lobe atelectasis (3-7 years) and 14 healthy children (3-7 years). Lung
sounds at the bilateral fifth intercostal spaces on the midclavicular line were
recorded. The right-to-left ratio (R/L ratio) and the expiration to inspiration
ratio (E/I ratio) of the breath sound sound pressure were calculated separately
for three octave bands (100-200 Hz, 200-400 Hz, and 400-800 Hz). These data were
then compared between the atelectasis and control groups. In addition, the same
measurements were repeated after treatment, including RPT, in the atelectasis
group. RESULT: Before treatment, the inspiratory R/L ratios for all the frequency
bands were significantly lower in the atelectasis group than in the control
group, and the E/I ratios for all the frequency bands were significantly higher
in the atelectasis group than in the control group. After treatment, the
inspiratory R/L ratios of the atelectasis group did not increase significantly,
but the E/I ratios decreased for all the frequency bands and became similar to
those of the control group. CONCLUSION: Breath sound attenuation in the
atelectatic area remained unchanged even after radiographical resolution,
suggesting a continued decrease in local ventilation. On the other hand, the
elevated E/I ratio for the atelectatic area was normalized after treatment.
Therefore, the differences between inspiratory and expiration sound intensities
may be an important marker of atelectatic improvement in children.
PMID- 27611431
TI - Association between Hypoalbuminaemia and Mortality in Patients with Community
Acquired Bacteraemia Is Primarily Related to Acute Disorders.
AB - We sought to investigate whether hypoalbuminaemia was mainly caused by acute or
chronic factors in patients with community-acquired bacteraemia. In this
population-based study, we considered 1844 adult cases of community-acquired
bacteraemia that occurred in Funen, Denmark between 2000 and 2008. We used a
stepwise prognostic predisposition-insult-response-organ dysfunction (PIRO)
logistic regression model by initially including age and comorbidity, then added
bacterial species, and finally sepsis severity. The models were furthermore
analysed using receiver operating characteristic (ROC) curves. Outcomes comprised
mortality incidence on days 0-30 and 31-365 after the bacteraemia episode. Each
step was performed with and without baseline albumin level measured on the date
of bacteraemia. In 422 patients, their latest albumin measurement taken 8-30 days
before the date of bacteraemia was also used in the analysis together with the
baseline albumin level. For each decrease of 1g/L in plasma albumin level, the
odds ratios (95% confidence intervals) of mortality in the period of 0-30 days
after bacteraemia were 0.86 (0.84-0.88) in both predisposition (P) and
predisposition-insult (PI) models and 0.87 (0.85-0.89) in the full PIRO-model.
The AUC values were 0.78 and 0.66 for mortality in the period of 0-30 days in the
model comprising only predisposition factors with and without albumin levels
added as a factor, respectively. The AUC values in the full PIRO-model were 0.81
and 0.73 with and without consideration of albumin levels, respectively. A higher
proportion of patients died within 30 days if there was a decrease in the albumin
level between days 8 and 30 before bacteraemia and the actual bacteraemia date. A
single plasma albumin measurement on the bacteraemia date was a better prognostic
predictor of short-term mortality than the sepsis severity score.
PMID- 27611432
TI - Neuroprotection by alpha2-Adrenergic Receptor Stimulation after Excitotoxic
Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and
Their Distribution in the Chicken Retina.
AB - We have studied the effect of alpha2-adrenergic receptor stimulation on the total
excitotoxically injured chicken retinal ganglion cell population. N-methyl-D
aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a
positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted
retinas using automated routines. The number and distribution of the Brn3a+ RGCs
were analyzed in series of normal retinas from embryonic day 8 to post-hatch day
11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of
Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of
approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that
the density decreased with age as the retinal size increased. In contrast to
previous studies, we did not find any specific region with increased RGC density,
rather the Brn3a+ RGCs were homogeneously distributed over the central retina
with decreasing density in the periphery and in the region of the pecten oculli.
Injection of 5-10 MUg NMDA caused 30-50% loss of Brn3a+ cells and the loss was
more severe in the dorsal than in the ventral retina. Pretreatment with
brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and
the protective effect was higher in the dorsal than in the ventral retina. We
conclude that alpha2-adrenergic receptor stimulation reduced the impact of the
excitotoxic injury in chicken similarly to what has been shown in mammals.
Furthermore, the data show that the RGCs are evenly distributed over in the
retina, which challenges previous results that indicate the presence of specific
high RGC-density regions of the chicken retina.
PMID- 27611434
TI - Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in
Mumbai, India.
AB - BACKGROUND: Patients on linezolid-containing drug-resistant TB (DR-TB) regimen
often develop adverse-events, particularly peripheral and optic neuropathy.
Programmatic data and experiences of linezolid-associated optic neuropathy from
high DR-TB burden settings are lacking. The study aimed to determine the
frequency of and risk-factors associated with linezolid-associated optic
neuropathy and document the experiences related to treatment/care of DR-TB
patients on linezolid-containing regimens. METHODS: This was a retrospective
cohort study using routine clinical and laboratory data in Medecins Sans
Frontieres (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital &
Research Center, Mumbai, India. All DR-TB patients on linezolid-containing
treatment regimens were included in the study and underwent routine evaluations
for systemic and/or ocular complaints. Ophthalmological evaluation by a
consultant ophthalmologist included visual-acuity screening, slit-lamp
examination and dilated fundus examination. RESULTS: During January 2013-April
2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid
containing DR-TB treatment. The median age of these 86 patients was 25 (20-35)
years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24
(27.9%) had at least one episode of ocular complaints (the majority blurred
vision) and among them, five (5.8%) had optic neuropathy. Patients received
appropriate treatment and improvements were observed. None of the
demographic/clinical factors were associated with optic neuropathy in Poissons or
multivariate binary logistic-regression models. DISCUSSION: This is the first
report focusing on optic neuropathy in a cohort of complex DR-TB patients,
including patients co-infected with HIV, receiving linezolid-containing regimens.
In our study, one out of four patients on linezolid had at least one episode of
ocular complaints; therefore, systematic monitoring of patients by primary
physicians/nurses, and access to specialized diagnostic-services by specialists
are needed. As linezolid will be increasingly added to treatment regimens of DR
TB patients, programmes should allocate adequate resources for early diagnosis,
prevention and management of this disabling adverse event.
PMID- 27611436
TI - Sexual rights in Uganda and the struggle for meaning in community.
AB - Drawing on lessons from the experiences of women who exchange same-sex erotic
energies, this article suggests that advocates of same-sex human rights should
take into account epistemic erasures colonized people experience when activism
and policies regarding sexual freedom ignore various linguistic and community
structures that create spaces for diverse ways of knowing and being. Since the
late 1990s, the discourse on homosexuality in Uganda has motivated important
debates concerning human values of sovereignty, rights, and family, and has
expanded freedoms of sexual expression while at the same time conditioning these
freedoms to be experienced in colonial ways of self-knowledge. The language that
frames these debates continues to locate human rights for Ugandans who exchange
same-sex erotic energies outside the locales-family, history, and language-of
intelligible episteme for them. To make sense of this claim, I draw "exchange of
same-sex erotic energies" from a saying in Rukiga language spoken by Bakiga in
southwestern Uganda, okugira omukago mukika nikwokunywaana oruganda, to think
about family and community in which same-sex erotic energies are lived and
experienced. This article attempts to redirect attention from colonial
constructions of homosexuality to indigenous and decolonial perspectives in
relation to women in Uganda who exchange same-sex erotic energies in their
struggle for meaning in community. I argue for pedagogies and epistemologies of
place and memory in the struggle for human rights and sexual rights.
PMID- 27611435
TI - Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with
Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins
Involved in Cytoskeletal Regulation.
AB - Inhalation anesthetics are used to decrease the spinal cord transmission of
painful stimuli. However, the molecular or biochemical processes within cells
that regulate anesthetic-induced responses at the cellular level are largely
unknown. Here, we report the phosphoproteome profile of SH-SY5y human
neuroblastoma cells treated with sevoflurane, a clinically used anesthetic.
Phosphoproteins were isolated from cell lysates and analyzed using two
dimensional gel electrophoresis. The phosphorylation of putative anesthetic
responsive marker proteins was validated using western blot analysis in cells
treated with both sevoflurane and isoflurane. A total of 25 phosphoproteins were
identified as differentially phosphorylated proteins. These included key
regulators that signal cytoskeletal remodeling steps in pathways related to
vesicle trafficking, axonal growth, and cell migration. These proteins included
the Rho GTPase, Ras-GAP SH3 binding protein, Rho GTPase activating protein, actin
related protein, and actin. Sevoflurane and isoflurane also resulted in the
dissolution of F-actin fibers in SH-SY5y cells. Our results show that anesthetics
affect the phosphorylation of proteins involved in cytoskeletal remodeling
pathways.
PMID- 27611437
TI - Ivermectin-Activated, Cation-Permeable Glycine Receptors for the Chemogenetic
Control of Neuronal Excitation.
AB - The ability to control neuronal activation is rapidly advancing our understanding
of brain function and is widely viewed as having eventual therapeutic
application. Although several highly effective optogenetic, optochemical genetic,
and chemogenetic techniques have been developed for this purpose, new approaches
may provide better solutions for addressing particular questions and would
increase the number of neuronal populations that can be controlled independently.
An early chemogenetic neuronal silencing method employed a glutamate receptor Cl-
channel engineered for activation by 1-3 nM ivermectin. This construct has been
validated in vivo. Here, we sought to develop cation-permeable ivermectin-gated
receptors that were either maximally Ca2+-permeable so as to induce neuro
excitotoxic cell death or minimally Ca2+-permeable so as to depolarize neurons
with minimal excitotoxic risk. Our constructs were based on the human alpha1
glycine receptor Cl- channel due to its high conductance, human origin, high
ivermectin sensitivity (once mutated), and because pore mutations that render it
permeable to Na+ alone or Na+ plus Ca2+ are well characterized. We developed a
Ca2+-impermeable excitatory receptor by introducing the F207A/P-2'Delta/A
1'E/T13'V/A288G mutations and a Ca2+-permeable excitatory receptor by introducing
the F207A/A-1'E/A288G mutations. The latter receptor efficiently induces cell
death and strongly depolarizes neurons at nanomolar ivermectin concentrations.
PMID- 27611439
TI - Role of Telomerase in Cervical Lesions as Prognostic Marker: A Comparison Between
Immunohistochemistry and Fluorescence In Situ Hybridization.
AB - OBJECTIVES: Amplification of human telomerase is known to be associated with
cervical tumorigenesis, although its role in tumor progression of cervical
lesions is still unclear. We aimed to evaluate the role of telomerase in
predicting the evolution of cervical lesions. METHODS: A total of 50 tissue
samples taken by biopsy or conization once or repeatedly from 17 patients with
cervical lesions over a 14-year follow-up was analyzed using fluorescence in situ
hybridization (FISH) for hTERC gene alterations and immunohistochemistry (IHC)
for hTERT expression. The accuracy of the biomarkers was measured using the area
under the curve. RESULTS: Telomerase gene amplification is highly indicative of
cervical lesion evolution and seems to be a more reliable biomarker than the
protein expression detected by IHC. In fact, patients with benign lesions or
cervical intraepithelial lesions (CINs) showing hTERC amplification relapsed or
progressed into CIN 2 and CIN 3 more frequently than those without any gene
amplification. FISH and IHC assays had both 86% sensitivity on conized material
and 78% and 40% specificity, respectively. CONCLUSIONS: We demonstrated that the
most accurate method to evaluate telomerase alterations as prognostic markers in
cervical lesions was FISH assay on hTERC gene. The best accuracy was obtained
using conized materials.
PMID- 27611438
TI - Coupling Mechanism of Electromagnetic Field and Thermal Stress on Drosophila
melanogaster.
AB - Temperature is an important factor in research on the biological effects of
extremely low-frequency electromagnetic field (ELF-EMF), but interactions between
ELF-EMF and temperature remain unknown. The effects of ELF-EMF (50 Hz, 3 mT) on
the lifespan, locomotion, heat shock response (HSR), and oxidative stress (OS) of
Canton-Special (CS) and mutant w1118 flies were investigated at 25 degrees C and
35 degrees C (thermal stress). Results showed that thermal stress accelerated the
death rates of CS and w1118 flies, shortened their lifespan, and influenced their
locomotion rhythm and activity. The upregulated expression levels of heat shock
protein (HSP) 22, HSP26, and HSP70 indicated that HSR was enhanced. Thermal
stress-induced OS response increased malondialdehyde content, enhanced superoxide
dismutase activity, and decreased reactive oxygen species level. The effects of
thermal stress on the death rates, lifespan, locomotion, and HSP gene expression
of flies, especially w1118 line, were also enhanced by ELF-EMF. In conclusion,
thermal stress weakened the physiological function and promoted the HSR and OS of
flies. ELF-EMF aggravated damages and enhanced thermal stress-induced HSP and OS
response. Therefore, thermal stress and ELF-EMF elicited a synergistic effect.
PMID- 27611440
TI - Sleep Duration and Cancer in the NIH-AARP Diet and Health Study Cohort.
AB - BACKGROUND: Very few studies have examined sleep duration in relation to cancer
incidence with the exception of breast cancer. METHODS: We assessed the
associations between sleep duration and incidences of total and 18 site-specific
cancers in the NIH-AARP Health and Diet Study cohort, with 173,327 men and
123,858 women aged 51-72 years at baseline. Self-reported sleep duration
categories were assessed via questionnaire. We used multivariable Cox
proportional hazards regression to estimate hazard ratios (HR) and 95% confidence
intervals (CI), using 7-8 hours/night as the reference. RESULTS: We observed a
significantly increased risk of stomach cancer among male short sleepers
(multivariable HR5-6 vs. 7-8 hours = 1.29; 95%CI: 1.05, 1.59; Ptrend = 0.03). We
also observed suggestive associations in either short or long sleepers, which did
not reach overall significance (Ptrend >0.05), including increased risks in male
short sleepers for cancers of head and neck (HR<5vs.7-8 hours = 1.39; 95%CI:1.00
1.95), bladder (HR5-6vs.7-8 hours = 1.10; 95%CI:1.00-1.20), thyroid (HR<5 vs. 7-8
hours = 2.30; 95%CI:1.06, 5.02), Non-Hodgkin Lymphoma (NHL) (HR5-6vs.7-8 hours =
1.17; 95%CI:1.02-1.33), and myeloma (HR<5vs.7-8 hours = 2.06; 95%CI:1.20-3.51).
In women, the suggestive associations include a decreased total cancer risk
(HR<5vs.7-8 hours = 0.9; 95%CI:0.83-0.99) and breast cancer risk (HR<5vs.7-8
hours = 0.84; 95%CI:0.71-0.98) among short sleepers. A decreased ovarian cancer
risk (HR>= 9 vs. 7-8 hours = 0.50; 95%CI:0.26-0.97) and an increased NHL risk
(HR>= 9 vs. 7-8 hours = 1.45; 95%CI:1.00-2.11) were observed among long sleepers.
CONCLUSION: In an older population, we observed an increased stomach cancer risk
in male short sleepers and suggestive associations with short or long sleep
duration for many cancer risks in both genders.
PMID- 27611442
TI - Utility of electroencephalography: Experience from a U.S. tertiary care medical
center.
AB - OBJECTIVE: To investigate the utility of electroencephalography (EEG) for
evaluation of patients with altered mental status (AMS). METHODS: We
retrospectively reviewed 200 continuous EEGs (cEEGs) obtained in ICU and non-ICU
wards and 100 spot EEGs (sEEGs) obtained from the emergency department (ED) of a
large tertiary medical center. Main outcomes were access time (from study request
to hookup), and diagnostic yield (percentage of studies revealing significant
abnormality). RESULTS: Access time, mean+/-SD (maximum), was 3.5+/-3.2 (20.8)
hours in ICU, 4.8+/-5.0 (25.6) hours in non-ICU, and 2.7+/-3.6 (23.9) hours in
ED. Access time was not significantly different for stat requests or EEGs with
seizure activity. While the primary indication for EEG monitoring was to evaluate
for seizures as the cause of AMS, only 8% of cEEGs and 1% of sEEGs revealed
seizures. Epileptiform discharges were detected in 45% of ICU, 24% of non-ICU,
and 9% of ED cases, while 2% of ICU, 15% of non-ICU, and 45% of ED cases were
normal. CONCLUSIONS: Access to EEG is hampered by significant delays, and in
emergency settings, the conventional EEG system detects seizures only in a
minority of cases. SIGNIFICANCE: Our findings underscore the inefficiencies of
current EEG infrastructure for accessing diagnostically important information, as
well as the need for more prospective data describing the relationship between
EEG access time and EEG findings, clinical outcomes, and cost considerations.
PMID- 27611441
TI - Seroprevalence of Enterovirus A71 and Coxsackievirus A16 in Healthy People in
Shandong Province, China.
AB - BACKGROUND: Hand, foot, and mouth disease has become very common in mainland of
China in recent years, and enterovirus A71 and coxsackievirus A16 are its major
etiologic factors. Here we investigated the seroprevalence of enterovirus A71 and
coxsackievirus A16 based on a large group of healthy individuals in Shandong
province, China. METHODS: A total of 1378 healthy individuals were tested for
serum neutralizing antibodies against enterovirus A71 and coxsackievirus A16
using a micro neutralization test. RESULTS: The overall seroprevalence of
enterovirus A71 neutralizing antibodies was 74.75%. It increased significantly
from 48.84% in children aged 0-1 years old to 88.64% in those aged 20-29 years (p
< 0.01) and decreased to 85.71% in adults > 40 years old with a significant
gender-specific difference (p < 0.01). The overall coxsackievirus A16 antibody
prevalence was 71.77%. It increased significantly from 39.53% in children aged 0
1 years to 80.68% in those aged 10-19 years (p < 0.01) and decreased to 75.63% in
adults >40 years without a gender-specific difference. Nearly 50% of the children
<1 year were susceptible to enterovirus A71 infection versus 40% to
coxsackievirus A16 infection. Sample collection time and place also played a role
in the enterovirus A71 and coxsackievirus A16 positive rates. The overall rates
in January were significantly lower than those in April and August (p < 0.01);
enterovirus A71 positive rates in Jinan city (capital city of Shandong province)
were lower than those in Jining city and Zibo city (p < 0.05); and oxsackievirus
A16 positive rates in Jining city were significantly higher than those in Jinan
city and Zibo city (p < 0.01). CONCLUSION: There were significant differences
among age groups, locations, and time points in the seroprevalence rates of
enterovirus A71 and coxsackievirus A16 neutralizing antibodies in healthy people
in Shandong province.
PMID- 27611443
TI - On shifting the blame to humanity: Historicist narratives regarding transgressors
evoke compassion for the transgressor but disdain for humanity.
AB - People respond compassionately to transgressors whose immorality is rooted in an
unfortunate life history. But, are reactions to such historicist narratives
uniformly compassionate? We suggest not. We propose that historicist narratives
also have a dark side. Specifically, they encourage blame shifting, in which
negative evaluations of humanity arise hand in hand with compassion for the focal
transgressor of the narrative. Indeed, historicist narratives portray the focal
transgressor as victimized by multiple others, who destroy her goodness and
remove her chance to flourish in life. This destruction of another's potential is
itself a profound moral violation and thus activates far-reaching blame responses
that feed a disdainful view of humanity. In three studies, we provide evidence
that historicist narratives evoke compassion for one but disdain for the
multitude. We show that the resulting disdain can diminish prosocial behaviour in
unrelated contexts, that it is elicited by both experimenter-provided and
participant-generated historicist narratives, and that it is created via blame
shifting. Our findings question the assumption that proliferation of historicist
thinking would necessarily contribute to creating a more compassionate, humane
society.
PMID- 27611444
TI - Factors influencing the decision to comply with nurse recommendations to take or
avoid influenza vaccination.
AB - Influenza is a major cause of morbidity and mortality. Although vaccination is an
efficient means of prevention, low rates of vaccination are reported
periodically. The study aimed to examine factors affecting acceptance of nurses'
recommendations to take or avoid influenza vaccination. Study design was quasi
experimental with a 2 * 2 between subjects design: two variables were manipulated
and two were not. The research variables were expertise (of nurses and
respondents), type of recommendation (to vaccinate or not) and respondents' a
priori intention to vaccinate. Data were collected from 374 respondents. The
study was scenario based, differing in nurse expertise and type of
recommendation. After each scenario, the respondents were requested to indicate
their a-priori intention to vaccinate and to complete questionnaires on epistemic
authority (EA) attributed to the nurse, and of self-epistemic authority (SEA).
There is a general tendency to avoid vaccination. Intention to vaccinate
correlated positively with nurse recommendations, respondent a-priori intention
and nurse expertise. A significant three-way interaction between respondents'
SEA, nurse recommendations and nurse expertise was found. The nurse's
recommendation has the strongest effect when the nurse is an expert and the
respondent perceives him/herself as having high self-EA. The results highlight
the importance of patients' sense of knowledge for assuring their co-operation
and compliance with medical recommendations.
PMID- 27611445
TI - Structural basis for the reversibility of proton pyrophosphatase.
AB - Proton Pyrophosphatase (H+-PPase) is an evolutionarily conserved enzyme regarded
as a bona fide vacuolar marker. However, H+-PPase also localizes at the plasma
membrane of the phloem, where, evidence suggests that it functions as a
Pyrophosphate Synthase and participates in phloem loading and photosynthate
partitioning. We believe that this pyrophosphate synthesising function of H+
PPase is fundamentally rooted to its molecular structure, and here we postulate,
on the basis of published crystal structures of membrane-bound pyrophosphatases,
a plausible mechanism of pyrophosphate synthesis.
PMID- 27611447
TI - Timing and patterns of recurrence in epithelial ovarian cancer patients with no
gross residual disease after primary debulking surgery.
AB - OBJECTIVE: The aim of this study was to analyse patterns and timing of recurrence
and their association with clinical outcomes in recurrent epithelial ovarian
cancer (EOC) patients with no gross residual disease after primary debulking
surgery (PDS). METHODS: This study was conducted on 303 EOC patients with no
residual disease after PDS who were treated at the Samsung Medical Center from
2002 to 2012. By reviewing electronic medical records, information on date of
clinical/pathological recurrence and pattern of disease presentation for each
relapse were retrieved. RESULTS: Within a median follow-up of 53 months (range 3
156), 88 recurrences (29.0%) and 28 cancer-related deaths (9.2%) were observed.
Most of the recurrences were distant, discrete and transcoelomic. After complete
cytoreduction, the initial stage was associated with location of recurrence, but
not with recurrence patterns. Complete cytoreduction reduced the number of
recurrences, but it did not affect timing of recurrence. In multivariate analysis
for overall survival (OS), patients with distant recurrence, diffuse
carcinomatosis and mixed spread pattern of transcoelomic, lymphatic and
haematogenous recurrence were found to have higher risk. CONCLUSIONS: We found
that timing of recurrence was not affected by complete cytoreduction. Location,
type and pattern of recurrence were also significant prognostic factors for OS,
in addition to known prognostic predictors such as platinum sensitivity.
PMID- 27611446
TI - Smooth muscle-generated methylglyoxal impairs endothelial cell-mediated
vasodilatation of cerebral microvessels in type 1 diabetic rats.
AB - BACKGROUND AND PURPOSE: Endothelial cell-mediated vasodilatation of cerebral
arterioles is impaired in individuals with Type 1 diabetes (T1D). This defect
compromises haemodynamics and can lead to hypoxia, microbleeds, inflammation and
exaggerated ischaemia-reperfusion injuries. The molecular causes for
dysregulation of cerebral microvascular endothelial cells (cECs) in T1D remains
poorly defined. This study tests the hypothesis that cECs dysregulation in T1D is
triggered by increased generation of the mitochondrial toxin, methylglyoxal, by
smooth muscle cells in cerebral arterioles (cSMCs). EXPERIMENTAL APPROACH:
Endothelial cell-mediated vasodilatation, vascular transcytosis inflammation,
hypoxia and ischaemia-reperfusion injury were assessed in brains of male Sprague
Dawley rats with streptozotocin-induced diabetes and compared with those in
diabetic rats with increased expression of methylglyoxal-degrading enzyme
glyoxalase-I (Glo-I) in cSMCs. KEY RESULTS: After 7-8 weeks of T1D, endothelial
cell-mediated vasodilatation of cerebral arterioles was impaired. Microvascular
leakage, gliosis, macrophage/neutrophil infiltration, NF-kappaB activity and TNF
alpha levels were increased, and density of perfused microvessels was reduced.
Transient occlusion of a mid-cerebral artery exacerbated ischaemia-reperfusion
injury. In cSMCs, Glo-I protein was decreased, and the methylglyoxal-synthesizing
enzyme, vascular adhesion protein 1 (VAP-1) and methylglyoxal were increased.
Restoring Glo-I protein in cSMCs of diabetic rats to control levels via gene
transfer, blunted VAP-1 and methylglyoxal increases, cECs dysfunction,
microvascular leakage, inflammation, ischaemia-reperfusion injury and increased
microvessel perfusion. CONCLUSIONS AND IMPLICATIONS: Methylglyoxal generated by
cSMCs induced cECs dysfunction, inflammation, hypoxia and exaggerated ischaemia
reperfusion injury in diabetic rats. Lowering methylglyoxal produced by cSMCs may
be a viable therapeutic strategy to preserve cECs function and blunt deleterious
downstream consequences in T1D.
PMID- 27611449
TI - Surgical repair of a truncus arteriosus with unilateral absence of the right
proximal pulmonary artery.
AB - The unilateral absence of a proximal pulmonary artery (UAPPA) is rare and is most
frequently accompanied by cardiovascular anomalies such as tetralogy of Fallot or
septal defects. We report a patient with truncus arteriosus with UAPPA in which
we performed a two-stage surgical repair. During the first palliative operation,
a right modified Blalock-Taussig shunt was constructed to develop the hypoplastic
right pulmonary artery. At 10 months, the patient underwent patch closure of a
ventricular septal defect with integration of both pulmonary arteries, and
reconstruction of the right ventricular outflow tract using a conduit. Four years
postoperatively, he continues to do well.
PMID- 27611448
TI - CT Pulmonary Angiography at Reduced Radiation Exposure and Contrast Material
Volume Using Iterative Model Reconstruction and iDose4 Technique in Comparison to
FBP.
AB - PURPOSE: To assess image quality of CT pulmonary angiography (CTPA) at reduced
radiation exposure (RD-CTPA) and contrast medium (CM) volume using two different
iterative reconstruction (IR) algorithms (iDose4 and iterative model
reconstruction (IMR)) in comparison to filtered back projection (FBP). MATERIALS
AND METHODS: 52 patients (body weight < 100 kg, mean BMI: 23.9) with suspected
pulmonary embolism (PE) underwent RD-CTPA (tube voltage: 80 kV; mean CTDIvol: 1.9
mGy) using 40 ml CM. Data were reconstructed using FBP and two different IR
algorithms (iDose4 and IMR). Subjective and objective image quality and
conspicuity of PE were assessed in central, segmental, and subsegmental arteries.
RESULTS: Noise reduction of 55% was achieved with iDose4 and of 85% with IMR
compared to FBP. Contrast-to-noise ratio significantly increased with iDose4 and
IMR compared to FBP (p<0.05). Subjective image quality was rated significantly
higher at IMR reconstructions in comparison to iDose4 and FBP. Conspicuity of
central and segmental PE significantly improved with the use of IMR. In
subsegmental arteries, iDose4 was superior to IMR. CONCLUSIONS: CTPA at reduced
radiation exposure and contrast medium volume is feasible with the use of IMR,
which provides improved image quality and conspicuity of pulmonary embolism in
central and segmental arteries.
PMID- 27611450
TI - Correction: Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene
Expression and Defense Responses.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1004936.].
PMID- 27611451
TI - Caffeine metabolites not caffeine protect against riboflavin photosensitized
oxidative damage related to skin and eye health.
AB - Caffeine metabolites were found to bind riboflavin with dissociation constant in
the millimolar region by an exothermic process with positive entropy of reaction,
which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly
by hydrogen bonding with water being released from riboflavin solvation shell
upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl
uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser
flash photolysis to be efficient as quenchers of triplet riboflavin with second
order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1),
respectively, in aqueous solution of pH6.4 at 25 degrees C and more efficient
than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate
constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non
reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine
seem accordingly important for the observed protective effect against cutaneous
melanoma identified for drinkers of regular but not of decaffeinated coffee. The
caffeine metabolites, but not caffeine, were by time resolved single photon
counting found to quench singlet excited riboflavin through exothermic formation
of ground-state precursor complexes indicating importance of hydrogen bounding
through keto-enol tautomer's for protection of oxidizable substrates and
sensitive structures against riboflavin photosensitization.
PMID- 27611452
TI - Is it possible to study the kinetic parameters of interaction between PNA and
parallel and antiparallel DNA by stopped-flow fluorescence?
AB - Peptide nucleic acids (PNAs) are among the most interesting and versatile
artificial structural mimics of nucleic acids and exhibit peculiar and important
properties (i.e. high chemical stability, and a high resistance to cellular
enzymes and nucleases). Despite their unnatural structure, they are able to
recognize and bind DNA and RNA in a very high, specific and selective manner. One
of the most popular, easy and reliable method to measure the stability of PNA-DNA
hybrid systems is the melting temperature but the thermodynamic data are obtained
using a big quantity of materials failing to provide information on the kinetics
of the interaction. In the present work, the PNA decamer 6, with the TCACTAGATG
sequence of nucleobases, and the corresponding fluorescent PNA-FITU (fluorescein
isothiourea) decamer 8 were synthesized with standard manual Boc-based chemistry.
The interaction of the PNA-FITU with parallel and antiparallel DNA has been
studied by stopped-flow fluorescence, which is proposed as an alternative
technique to obtain the kinetic parameters of the binding. The great advantage of
using the stopped-flow technique is the possibility of studying the kinetics of
the PNA-DNA duplex formation in a physiological environment. In particular,
fluorescence stopped-flow technique has been exploited to compare the affinity of
two PNA-DNA duplexes since it can discriminate between parallel and antiparallel
DNA binding.
PMID- 27611453
TI - Effects of low-level laser therapy on bone healing of critical-size defects
treated with bovine bone graft.
AB - OBJECTIVE: To histomorphometrically analyze the effect of low-level laser therapy
(LLLT) on bone formation process in surgically created critical-size defects
(CSDs) treated with bovine bone graft (BBG) and its influence over particles'
resorption of BBG. METHODS: A 10-mm diameter CSD was surgically created in the
calvaria of 64 male rats, which were distributed into 4 experimental groups: the
C group (control), only blood clot; the LLLT group, LLLT (GaAlAs, 660nm) and
blood clot; the BBG group, CSD filled with BBG; the BBG/LLLT group, LLLT and CSD
filled with BBG. Animals were euthanized at either 30 or 60days post-operation. A
histological analysis was performed. Additionally, the percentage of newly formed
bone area (NFBA) and remaining particles areas (RPA) of BBG were histometrically
evaluated and data statistically analyzed. RESULTS: The LLLT (5.82+/-2.05; 7.34+/
1.01) group presented significantly greater NFBA when compared to the C group
(1.61+/-0.30; 5.59+/-0.94) at 30 and 60days post-operation (p<0.05). The BBG/LLLT
group (7.39+/-1.45; 9.44+/-2.36) presented significantly greater NFBA than the
BBG group (3.85+/-1.56; 8.02+/-0.63) at 30 and 60days postoperation (p<0.05).
There was no significant difference in the mean percentage of implanted material
RPA between the BBG and the BBG/LLLT groups. CONCLUSIONS: LLLT can improve bone
formation process in CSD filled or not with BBG in rat calvaria, but it is not
able to accelerate particles resorption of this material in the interior of bone
defect.
PMID- 27611454
TI - Photo-mediated green synthesis of silver and zinc oxide nanoparticles using
aqueous extracts of two mangrove plant species, Heritiera fomes and Sonneratia
apetala and investigation of their biomedical applications.
AB - Green synthesis by using biological agents has been a simple and effective
approach for the synthesis of various forms of nanoparticles. The present
investigation was intended to synthesis Ag-NPs and ZnO-NPs under photo-condition
using the aqueous extracts of two mangrove plants namely Heritiera fomes and
Sonneratia apetala and evaluate their potential biomedical applications. The
formation of nanoparticles in aqueous solution of H. fomes and S. apetala under
exposure to sun light was validated by change in color and formation of
monodispersed NPs with a narrow particle size distribution. Fourier transform
infrared spectroscopy (FT-IR) reveals the presence of Oxime and other
heterocyclic compounds to be the most probable compounds responsible for the
reduction and stability of nanoparticles in the solutions. The synthesized NPs
displayed moderate free radical scavenging properties. The anti-inflammatory
potential of ZnO-NPs was recorded to be comparatively higher than that of Ag-NP
with 79% and 69.1% respectively. The Ag-NPs with unique properties of inhibiting
alpha-amylase (91.14% and 89.16%) were found to be significantly high indicating
its antidiabetic property. The synthesized NPs showed varied zone of inhibition
(9-16mm) against the tested microbial pathogens. The synthesized nanoparticles
possess strong biological activities in terms of antioxidant, anti-inflammatory,
antidiabetic and antibacterial, potentials which could be utilized in various
biological applications by the cosmetic, food and biomedical industries.
PMID- 27611457
TI - The Costs of Medical Privacy Breach.
PMID- 27611456
TI - Clinicopathological Features of Telbivudine-Associated Myopathy.
AB - Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for
chronic hepatitis B infection. While raised serum creatine kinase is common,
myopathy associated with telbivudine is rare. Reports on its myopathological
features are few and immunohistochemical analyses of inflammatory cell
infiltrates have not been previously described. We describe the clinical,
myopathological and immunohistochemical features of four patients who developed
myopathy after telbivudine therapy for chronic hepatitis B infection. All four
patients presented with progressive proximal muscle weakness, elevation of serum
creatine kinase and myopathic changes on electromyography. Muscle biopsies showed
myofiber degeneration/necrosis, regeneration, and fibers with cytoplasmic bodies
and cytochrome c oxidase deficiency. There was minimal inflammation associated
with strong sarcolemmal overexpression of class I major histocompatibility
complex (MHC class I). Upon withdrawal of telbivudine, muscle weakness improved
in all patients and eventually completely resolved in three. In our series,
telbivudine-associated myopathy is characterized by necrotizing myopathy which
improved on drug withdrawal. Although the occasional loss of cytochrome c oxidase
is consistent with mitochondrial toxicity, the overexpression of MHC class I in
all patients could suggest an underlying immune-mediated mechanism which may
warrant further investigation.
PMID- 27611458
TI - Aid in Dying Means Dignity for Patients.
PMID- 27611455
TI - T Helper 1 (Th1), Th2, and Th17 Responses to Leishmania major Lipophosphoglycan
3.
AB - Leishmania major is the main causal agent of cutaneous leishmaniasis (CL) that
remains a serious public health concern in many tropical and subtropical
countries. A long-lasting protective vaccine against leishmaniasis remains as a
medical unmet need. Lipophosphoglycan 3 (LPG3) is one of the class II LPG genes
from HSP90 family involved in the host immune responses. The aim of the present
study is to investigate the capability of recombinant LPG3 (rLPG3) to induce Th1,
Th2, Th17 responses. The results showed that rLPG3 in moderate and high
concentrations significantly induced expression of Th1 lineage-specific
transcription factor (T-bet) and cytokine (IFN-gamma)(P < 0.05). Moreover, the
Th1-stimulating effect of rLPG3 was confirmed by significant induction of IFN
gamma secretion from treated T cells (P < 0.01). However, no significant effect
of rLPG3 on Th2 and Th17 lineage cells was observed even in high concentration.
Our findings demonstrate that rLPG3 induces Th1, but not Th2 and Th17, lineage
responses. Further studies are needed to investigate adjuvant properties of rLPG3
for leishmania therapy.
PMID- 27611459
TI - Hospitals Working to Improve Population Health.
PMID- 27611461
TI - Embracing Technology to Connect Your Patients.
PMID- 27611460
TI - An Interview with Bernie Flynn: Insights into Leading a New Jersey Insurance
Comapny.
PMID- 27611462
TI - Top Tips for Physicians: getting the most out of your parntership with your
broker.
PMID- 27611463
TI - Standardized Testing in Medical School: Making Peace with the Process.
PMID- 27611464
TI - Relative contributions of bleeding scores and iron status on health-related
quality of life in von Willebrand disease: a cross-sectional study.
AB - INTRODUCTION: von Willebrand disease (VWD) is the most common inherited bleeding
disorder known in humans. Currently, studies investigating the health-related
quality of life (HR-QoL) in VWD using standardized tools are limited,
particularly among patients with mild decreases in von Willebrand factor or
activity. AIM: To determine HR-QoL and its predictors among patients with mild,
moderate and severe forms of VWD. METHODS: Patients with clinical diagnosis of
VWD were recruited from a tertiary Inherited Bleeding Disorder Clinic. Upon
informed consent, bleeding scores were obtained via a standardized, self
administered tool. Each participant also completed a HR-QoL questionnaire (SF
36). Analyses included paired t-test, independent t-test, one-way anova and
multivariate regression. RESULTS: A total of 102 patients were recruited (consent
rate = 95%). Participants were 38 years on average (SD 14.8), 78% were female and
80% were diagnosed with VWD Type 1. Compared to age- and sex-matched normative
data, VWD patients had clinically and statistically significant reductions in
seven of eight HR-QoL domains and the physical and mental component summaries.
Adjusted for age, sex, socioeconomic status and rurality, there was a trend
towards lower physical component summary with increasing bleeding score, and
lower mental domains with iron deficiency status (P = 0.07 and P = 0.08
respectively). CONCLUSION: This study is the first to examine the impact of VWD
on HR-QoL across disease severity while incorporating socioeconomic status and
rurality. Significant reductions in HR-QoL among VWD patients, especially the
relationship between iron status and mental HR-QoL, strengthen the rationale for
prospective studies to evaluate the efficacy of iron replacement in this setting.
PMID- 27611465
TI - A clozapine paradox?
PMID- 27611466
TI - Do Xpert MTB/RIF Cycle Threshold Values Provide Information about Patient Delays
for Tuberculosis Diagnosis?
AB - INTRODUCTION: Early diagnosis and initiation to appropriate treatment is vital
for tuberculosis (TB) control. The XpertMTB/RIF (Xpert) assay offers rapid TB
diagnosis and quantitative estimation of bacterial burden through Cycle threshold
(Ct) values. We assessed whether the Xpert Ct value is associated with delayed TB
diagnosis as a potential monitoring tool for TB control programme performance.
MATERIALS AND METHODS: This analysis was nested in a prospective study under the
routine TB surveillance procedures of the National TB Control Program in Manhica
district, Maputo province, Mozambique. Presumptive TB patients were tested using
smear microscopy and Xpert. We explored the association between Xpert Ct values
and self-reported delay of Xpert-positive TB patients as recorded at the time of
diagnosis enrolment. Patients with >60 days of TB symptoms were considered to
have long delays. RESULTS: Of 1,483 presumptive TB cases, 580 were diagnosed as
TB of whom 505 (87.0%) were due to pulmonary TB and 302 (94.1%) were Xpert
positive. Ct values (range, 9.7-46.4) showed a multimodal distribution. The
median (IQR) delay was 30 (30-45) days. Ct values showed no correlation with
delay (R2 = 0.001, p = 0.621), nor any association with long delays: adjusted
odds ratios (AOR) (95% confidence interval [CI]) comparing to >28 cycles 0.99
(0.50-1.96; p = 0.987) for 23-28 cycles, 0.93 (0.50-1.74; p = 0.828) for 16-22
cycles; and 1.05 (0.47-2.36; p = 0.897) for <16 cycles. Being HIV-negative (AOR
[95% CI]), 2.05 (1.19-3.51, p = 0.009) and rural residence 1.74 (1.08-2.81, p =
0.023), were independent predictors of long delays. CONCLUSION: Xpert Ct values
were not associated with patient delay for TB diagnosis and cannot be used as an
indicator of TB control program performance.
PMID- 27611467
TI - Variation in the Dicer and RAN Genes Are Associated with Survival in Patients
with Hepatocellular Carcinoma.
AB - Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect
microRNA processing and subsequently impact tumorigenesis. The aim of this study
was to investigate the associations between SNPs in microRNA machinery genes and
hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in
microRNA machinery genes was performed using blood samples from 147 patients with
HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery
genes were significantly associated with HCC development. However, among the
models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719
and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C
C-C) showed synergistic effects in terms of an increased risk of HCC development
(odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002).
Multivariate Cox proportional hazard regression analysis showed a significant
survival benefit for the DICER rs3742330 GG compared with the AA type (hazard
ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT
compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044).
Although we found no direct association between DICER (rs3742330 and rs13078),
DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and
HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were
associated with the survival of HCC patients. Future studies with larger samples
are needed to determine associations of SNPs in microRNA machinery genes with HCC
risk and prognosis.
PMID- 27611468
TI - Novel Electrospun Dual-Layered Composite Nanofibrous Membrane Endowed with
Electricity-Magnetism Bifunctionality at One Layer and Photoluminescence at the
Other Layer.
AB - Dual-layered composite nanofibrous membrane equipped with electrical conduction,
magnetism and photoluminescence trifunctionality is constructed via
electrospinning. The composite membrane consists of a polyaniline (PANI)/Fe3O4
nanoparticles (NPs)/polyacrylonitrile (PAN) tuned electrical-magnetic
bifunctional nanofibrous layer at one side and a
Eu(TTA)3(TPPO)2/polyvinylpyrrolidone (PVP) photoluminescent nanofibrous layer at
the other side, and the two layers are tightly combined face-to-face together
into the novel dual-layered composite membrane with trifunctionality. The
electric conductivity and magnetism of electrical-magnetic bifunctionality can be
respectively tunable via modulating the respective PANI and Fe3O4 NPs contents,
and the highest electric conductivity approaches the order of 1 * 10-2 S cm-1.
Predominant red emission at 615 nm can be obviously observed in the
photoluminescent layer under 366 nm excitation. Moreover, the luminescent
intensity of photoluminescent layer is almost unaffected by the electrical
magnetic bifunctional layer because of the fact that the photoluminescent
materials have been successfully isolated from dark-colored PANI and Fe3O4 NPs.
The novel dual-layered composite nanofibrous membrane with trifunctionality has
potentials in many fields. Furthermore, the design philosophy and fabrication
method for the dual-layered multifunctional membrane provide a new and facile
strategy toward other membranes with multifunctionality.
PMID- 27611470
TI - Luffa sponge offsets the negative effects of aeration on bacterial cellulose
production.
AB - AIMS: To offset the negative effects of aeration on bacterial cellulose (BC)
production by acetic acid bacteria using enmeshed cellulose microfibrils (CM) on
luffa sponge matrices (LSM). METHODS AND RESULTS: The CM were enmeshed on LSM
(LSM-CM). The optimal amount of LSM-CM was determined for BC production under
aerated conditions. Without LSM-CM, no BC was produced in seven out of nine
production cycles at the highest aeration rate (9 l min-1 ). However, with 0.5%
LSM-CM and an aeration rate of 3 l min-1 , a satisfactory oxygen transfer
coefficient was achieved, and also a good yield of BC (5.24 g l-1 ). Moreover,
the LSM-CM was able to be recycled through nine consecutive BC production cycles.
The highest BC yields (from 5.8 +/- 0.4 to 6.6 +/- 0.4 g l-1 ) were associated
with high bacterial biomass and this was confirmed by scanning electron
microscopy. CONCLUSIONS: We confirm that LSM-CM works well as a starter.
Microenvironments low in dissolved oxygen within the matrices of LSM-CM are
important for BC production under aeration conditions. SIGNIFICANCE AND IMPACT OF
THE STUDY: The LSM-CM provides a microenvironment which offsets the negative
effects of aeration on BC production. A sustainable, economic process for mass BC
production is described using recycled LSM-CM with aeration.
PMID- 27611469
TI - Insulin Restores an Altered Corneal Epithelium Circadian Rhythm in Mice with
Streptozotocin-induced Type 1 Diabetes.
AB - The mechanisms of corneal epithelial lesions and delayed wound repair, as well as
their association with diabetes mellitus, are critical issues for clinical
ophthalmologists. To test whether the diabetic condition alters the circadian
rhythm in a mouse cornea and whether insulin can synchronise the corneal clock,
we studied the effects of streptozotocin-induced diabetes on the mitosis of
epithelial cells, the recruitment of leukocytes to the cornea, and the expression
of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbalpha) in the
corneal epithelium. We also assessed the possible effect of insulin on these
modifications. Diabetes downregulated Clock, Bmal1, and Per2 expression,
upregulated Cry1 and Rev-erbalpha expression, reduced corneal epithelial mitosis,
and increased leukocyte (neutrophils and gammadelta T-cells) recruitment to the
cornea. Early treatments with insulin partially restored the altered rhythmicity
in the diabetic cornea. In conclusion, insulin-dependent diabetes altered the
normal rhythmicity of the cornea, and insulin administration had a beneficial
effect on restoring normal rhythmicity in the diabetic cornea.
PMID- 27611471
TI - Pediatric blood transfusion practices at a regional referral hospital in Kenya.
AB - BACKGROUND: Severe anemia in children is a major public health problem in sub
Saharan Africa. In this study we describe clinical and operational aspects of
blood transfusion in children admitted to Coast Provincial General Hospital,
Kenya. STUDY DESIGN AND METHODS: This was an observational study where over a 2
year period, demographic and laboratory data were collected on all children for
whom the hospital blood bank received a transfusion request. Clinical data were
obtained by retrospective review of case notes over the first year. RESULTS:
There were 2789 requests for blood for children (median age, 1.8 years;
interquartile range [IQR], 0.6-6.6 years); 70% (1950) of the samples were
crossmatched with 85% (1663/1950) issued. Ninety percent (1505/1663) were
presumed transfused. Median time from laboratory receipt of request to collection
of blood was 3.6 hours (IQR, 1.4-12.8 hr). Case notes of 590 children were
reviewed and median pretransfusion hemoglobin level was 6.0 g/dL (IQR, 4.2-9.1
g/dL). Ninety-four percent (186) were transfused "appropriately" while 52% (120)
were transfused "inappropriately." There was significant disagreement between the
clinical and laboratory diagnosis of severe anemia (exact McNemar's test; p <
0.0001). Antimalarials were prescribed for 65% (259) of children who received
blood transfusions but only 41% (106) of these had a positive blood film.
CONCLUSION: In this setting, clinicians often order blood based on the clinical
impression of "severe anemia." This has implications for laboratory workload and
the blood supply itself. However, the majority of children with severe anemia
were appropriately transfused. The use of antimalarials with blood transfusions
irrespective of blood film results is common practice.
PMID- 27611472
TI - Magnetic bead-liposome hybrids enable sensitive and portable detection of DNA
methyltransferase activity using personal glucose meter.
AB - DNA methyltransferase (MTase) plays a critical role in maintaining genome
methylation patterns, which has a close relationship to cancer and bacterial
diseases. This encouraged the need to develop highly sensitive, simple, and
robust assays for DNA MTase detection and inhibitor screening. Herein, a simple,
sensitive, and specific DNA MTase activity assay was developed based on magnetic
beads-liposome hybrids combined with personal glucose meter (PGM) for
quantitative detection of DNA MTase and inhibitor screening. First, a magnetic
beads-liposome hybrid probe is designed by the hybridization of p1DNA
functionalized magnetic bead with p2DNA-functionalized glucoamylase-encapsulated
liposome (GEL). It integrates target recognition, magnetic separation and signal
amplification within one multifunctional design. Then, in the presence of Dam
MTase, the hybrids probe was methylated, and cleaved by methylation-sensitive
restriction endonuclease Dpn I, making liposome separated from magnetic bead by
magnetic separation. Finally, the separated liposome was decomposed, liberating
the encapsulated glucoamylase to catalyze the hydrolysis of the signal substrate
amylose with multiple turnovers, producing a large amount of glucose for
quantitative readout by the PGM. In the proposed assay, the magnetic beads
liposome hybrids offered excellent sensitivity due to primary amplification via
releasing numerous glucoamylase from a liposome followed by a secondary enzymatic
amplification. The use of portable quantitative device PGM bypasses the
requirement of complicated instruments and sophisticated operations, making the
method simple and feasible for on-site detection. Moreover, the proposed assay
was successfully applied in complex biological matrix and screen suitable
inhibitor drugs for DAM for disease(s) treatment. The results reveal that the
approach provides a simple, sensitive, and robust platform for DNA MTases
detection and screening potential drugs in medical research and early clinical
diagnostics.
PMID- 27611473
TI - Glutathione regulation-based dual-functional upconversion sensing-platform for
acetylcholinesterase activity and cadmium ions.
AB - A dual-functional platform for the sensing of acetylcholinesterase (AChE)
activity and cadmium ions (Cd2+) was developed based on the fluorescence
resonance energy transfer (FRET) between NaYF4:Yb,Er upconversion nanoparticles
(UCNPs) and gold nanoparticles (AuNPs) via glutathione regulation. The detection
mechanism is based on the fact that AuNPs can quench the fluorescence of UCNPs.
AChE catalyzes the hydrolysis of acetylthiocholine (ATC) into thiocholine which
reacts with AuNPs by S-Au conjunction and results the aggregation of AuNPs and
change in fluorescence of UCNPs. Therefore, the AChE activity can be detected
through the changes of the color of solution and fluorescence recovery of UCNPs.
However, the presence of glutathione (GSH) can protect AuNPs from aggregation and
enlarge the inter-particle distance between AuNPs and UCNPs. When Cd2+ is added
into the stable mixture of AuNPs, GSH and AChE/ATC, Cd2+ could interact with GSH
to form a spherical shaped (GSH)4Cd complex, which decreases the free GSH on the
surface of AuNPs to weaken the stability of AuNPs and lead to the easily
aggregation of them in the system. The aggregated-AuNPs are released from the
surface of UCNPs, which results in the fluorescence of UCNPs gradually recovered.
Under the optimized conditions, the detection limits of AChE activity and Cd2+
are estimated to be 0.015mU/mL and 0.2uM, respectively. The small molecules
regulated dual-functional platform based on UCNPs/AuNPs is a simple, label-free
method and can be applied for the turn-on fluorescence detection of AChE activity
in human serum and Cd2+ in real water samples. The present work demonstrates a
general strategy for the design of small molecules regulated multifunctional
platform and will be expanded for different areas in the future.
PMID- 27611474
TI - A simple G-quadruplex molecular beacon-based biosensor for highly selective
detection of microRNA.
AB - MicroRNAs (miRNAs) family members are usually different from each other in one
base variation. The high sequence homology poses a challenge for miRNA analysis
with single-base selectivity. On the basis of G-quadruplex molecular beacons
(G4MB) and duplex-specific nuclease (DSN), we developed a simple and highly
selective amplification biosensor for miRNA detection. G4MB with a G4 motif stem
is used as recognition probe. In the present of target miRNAs, G4MB hybridizes
with target miRNA perfectly and forms a G4MB-miRNA duplex. Then, DSN subsequently
cleaves the G4MB of the G4MB-miRNA duplex to recycle the target miRNA, which
leads to fluorescence signal amplification. In the absence of target miRNAs, DSN
can not digest the stem of G4MB because of the protection of G4 motif, which
eliminates the false positive signal, and produces low fluorescence background.
Importantly, the powerful discriminating abilities of both G4MB and DSN make the
novel sensor suitable for miRNAs detection with high single-base selectivity.
Comparing with traditional linear ssDNA probe-DSN-based method, the signal
response of similar miRNA sequences with one-base difference has been reduced
from 24% to 6% by using this G4MB-DSN-based method. Moreover, this simple sensor
also exhibits a good applicability in cancer cell samples and a multiplex
capability in one sample with different miRNA targets, making it a promising
strategy for clinical diagnostics.
PMID- 27611475
TI - Size-controlled preparation of peroxidase-like graphene-gold nanoparticle hybrids
for the visible detection of norovirus-like particles.
AB - A hybrid structure of graphene-gold nanoparticles (Grp-Au NPs) was designed as a
new nanoprobe for colorimetric immunoassays. This hybrid structure was prepared
using chloroauric acid, sodium formate and Grp flakes at room temperature. Au NPs
attached strongly onto the Grp surface, and their size was controlled by varying
the sodium formate concentration. The Raman intensity of the Grp-Au NP hybrids
was significantly enhanced at 1567cm-1 and 2730cm-1 compared with those of
pristine Grp because of the electronic interaction between Au NPs and Grp. The
Grp-Au NPs with a hybrid structure catalyzed the oxidation of the peroxidase
substrate 3,3,5,5-tetramethylbenzidine (TMB) with H2O2, developing a blue color
in aqueous solution. This catalytic activity was utilized to detect norovirus
like particles (NoV-LPs) in human serum. The enhanced colorimetric response was
monitored using Ab-conjugated-Grp-Au NPs and found to depend on the NoV-LP
concentration, exhibiting a linear response from 100pg/mL to 10MUg/mL. The limit
of detection (LOD) of this proposed method was 92.7pg/mL, 112 times lower than
that of a conventional enzyme-linked immunosorbent assay (ELISA). The sensitivity
of this test was also 41 times greater than that of a commercial diagnostic kit.
The selectivity of the Grp-Au NPs was tested with other viruses, and no color
changes were observed. Therefore, the proposed system will facilitate the
utilization of the intrinsic peroxidase-like activity of Grp-Au NPs in medical
diagnostics. We believe that the engineered catalytic Grp-Au NP hybrids could
find potential applications in the future development of biocatalysts and
bioassays.
PMID- 27611477
TI - Publishers' note.
PMID- 27611476
TI - Comparing the Health Effects of Ambient Particulate Matter Estimated Using Ground
Based versus Remote Sensing Exposure Estimates.
AB - BACKGROUND: Remote sensing (RS) is increasingly used for exposure assessment in
epidemiological and burden of disease studies, including those investigating
whether chronic exposure to ambient fine particulate matter (PM2.5) is associated
with mortality. OBJECTIVES: We compared relative risk estimates of mortality from
diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5
modeled using ground-level information. METHODS: We geocoded the baseline
residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II)
cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all
participants using seven different exposure models. Most of the exposure models
were averaged for the years 2002-2004, and one RS estimate was for a longer,
contemporaneous period. We used Cox proportional hazards regression to estimate
relative risks (RRs) for the association of PM2.5 with circulatory mortality and
ischemic heart disease. RESULTS: Estimates of mortality risk differed among
exposure models. The smallest relative risk was observed for the RS estimates
that excluded ground-based monitors for circulatory deaths [RR = 1.02, 95%
confidence interval (CI): 1.00, 1.04 per 10 MUg/m3 increment in PM2.5]. The
largest relative risk was observed for the land-use regression model that
included traffic information (RR = 1.14, 95% CI: 1.11, 1.17 per 10 MUg/m3
increment in PM2.5). CONCLUSIONS: We found significant associations between PM2.5
and mortality in every model; however, relative risks estimated from exposure
models using ground-based information were generally larger than those estimated
using RS alone.
PMID- 27611478
TI - Incorporation of a Valine-Leucine-Lysine-Containing Substrate in the Bacterial
Cell Wall.
AB - The emergence of antibiotic-resistant bacteria is a major public health threat,
and therefore novel antimicrobial targets and strategies are urgently needed. In
this regard, cell-wall-associated proteases are envisaged as interesting
antimicrobial targets due to their role in cell wall remodeling. Here, we
describe the discovery and characteristics of a protease substrate that is
processed by a bacterial cell-wall-associated protease. Stationary-phase grown
Gram-positive bacteria were incubated with fluorogenic protease substrates, and
their cleavage and covalent incorporation into the cell wall was analyzed. Of all
of the substrates used, only one substrate, containing a valine-leucine-lysine
(VLK) motif, was covalently incorporated into the bacterial cell wall. Linkage of
the VLK-peptide substrate appeared unrelated to sortase A and B activity, as both
wild-type and sortase A and B knock out Staphylococcus aureus strains
incorporated this substrate into their cell wall with comparable efficiency.
Additionally, the VLK-peptide substrate showed significantly higher incorporation
in the cell wall of VanA-positive Enterococcus faecium strains than in VanB- and
vancomycin-susceptible isolates. In conclusion, the VLK-peptide substrate
identified in this study shows promise as a vehicle for targeting antimicrobial
compounds and diagnostic contrast agents to the bacterial cell wall.
PMID- 27611479
TI - Qualitative study on decision-making by prostate cancer physicians during active
surveillance.
AB - OBJECTIVE: To explore and identify factors that influence physicians' decisions
while monitoring patients with prostate cancer on active surveillance (AS).
SUBJECTS AND METHODS: A purposive sampling strategy was used to identify
physicians treating prostate cancer from diverse clinical backgrounds and
geographic areas across the USA. We conducted 24 in-depth interviews from July to
December 2015, until thematic saturation was reached. The Applied Thematic
Analysis framework was used to guide data collection and analysis. Interview
transcripts were reviewed and coded independently by two researchers. Matrix
analysis and NVivo software were used for organization and further analysis.
RESULTS: Eight key themes emerged to explain variation in AS monitoring: (i)
physician comfort with AS; (ii) protocol selection; (iii) beliefs about the
utility and quality of testing; (iv) years of experience and exposure to AS
during training; (v) concerns about inflicting 'harm'; (vi) patient
characteristics; (vii) patient preferences; and (viii) financial incentives.
CONCLUSION: These qualitative data reveal which factors influence physicians who
manage patients on AS. There is tension between providing standardized care while
also considering individual patients' needs and health status. Additional
education on AS is needed during urology training and continuing medical
education. Future research is needed to empirically understand whether any
specific protocol is superior to tailored, individualized care.
PMID- 27611481
TI - Are Patient-reported Outcomes Correlated With Clinical Outcomes After Surgery?: A
Population-based Study.
AB - OBJECTIVE: To evaluate the extent to which patient-reported outcomes (PROs) (eg,
health-related quality of life) are distinct from clinical outcomes following
bariatric surgery. BACKGROUND: Hospital quality measurement often focuses on
traditional clinical outcomes (eg, complications). However, PROs may provide a
unique perspective regarding performance, particularly for common, low-risk
procedures. METHODS: We used data from 11,420 patients who underwent bariatric
surgery (2008-2012) from the Michigan Bariatric Surgery Collaborative (39
hospitals). We included both short-term (30-day complication rates) and long-term
(1-year weight loss and comorbidity resolution) outcomes. For PROs, we used
health-related quality of life assessed by the Health and Activities Limitations
Index (HALex) and Bariatric Quality of Life (BQL) index preoperatively and at 1
year. We used multivariable linear regression to determine the association
between these PROs and both short and long-term clinical outcomes, adjusting for
patient factors and the type of surgical procedure. RESULTS: After adjustment for
risk factors and surgical procedure, hospital rankings based on PROs (either the
average change in HALex or BQL scores) were not correlated with hospital rankings
based on complications. In contrast, both PRO measures were correlated with
weight loss. Specifically, the average change in HALex score (R = 0.24, P <
0.002) and average change in BQL score (R = 0.44, P < 0.001) were correlated with
hospital average percent excess. One PRO measure-BQL score-was correlated with a
decline in the need for medications due to associated comorbidities (R = 0.16, P
< 0.01). After accounting for short and long-term clinical outcomes, between 15%
and 44% of the variation in PROs remained unexplained at the hospital level.
CONCLUSIONS: Patient-reported outcomes are not correlated with early
perioperative events, but are correlated with measures of clinical effectiveness
after bariatric surgery. A comprehensive approach to surgical quality should
incorporate both clinical events and self-reported measures of health status
throughout the short and long-term recovery period.
PMID- 27611480
TI - p53-dependent up-regulation of CDKN1A and down-regulation of CCNE2 in response to
beryllium.
AB - OBJECTIVES: Beryllium salts (here, beryllium sulphate) can produce a cytostatic
effect in some cell types. The basis for this effect may include increased
expression of proliferation inhibitors, reduced expression of proliferation
promoters, or both. This study sought to determine the role of p53, the tumour
suppressing transcription factor, in mediating beryllium-induced cytostasis.
MATERIALS AND METHODS: Human A172 glioma cells express wild-type TP53 gene.
Activity of p53 was experimentally manipulated using siRNA and related
approaches. Key elements of the beryllium-response were compared in normal and
p53-knockdown A172 cells using RT-PCR and Western blotting. RESULTS: In A172
cells, 10 MUm BeSO4 caused 300% increase in CDKN1A (cyclin-dependent kinase
inhibitor p21) mRNA and 90% reduction of CCNE2 (cyclin E2) mRNA. The increased
p21 mRNA and reduced cyclin E2 mRNA were each dependent on presence of functional
p53. For p21, increased mRNA led to commensurately increased protein levels. In
contrast, reduction in cyclin E2 mRNA levels did not lead to corresponding
reductions in cyclin E2 protein. The proteasomal inhibitor MG-132 caused p53
protein to increase, but it had no effect on cyclin E2 protein levels.
Cycloheximide time course studies indicated that the cyclin E2 protein half-life
was more than 12 hours in these cells. CONCLUSIONS: Beryllium elicited p53
dependent changes in mRNA levels of key determinants of cell proliferation such
as p21 and cyclin E2. However, cyclin E2 protein appeared to be aberrantly
regulated in this cell type, as its turnover was unexpectedly slow.
PMID- 27611483
TI - Evaluating the potential of thermal read-out techniques combined with molecularly
imprinted polymers for the sensing of low-weight organic molecules.
AB - In recent years, there has been a tremendous increase in the papers published on
synthetic recognition elements. Molecularly imprinted polymers (MIPs), also
referred to as "man-made mimics" of antibodies, are able to rebind their template
molecules with high affinity. Advantages compared with those of natural receptors
include their excellent thermal and chemical stability, low cost, and ease of the
production process. However, their use in commercial biosensors is limited owing
to the difficulty to incorporate MIPs into suitable sensing platforms and
traditional detection techniques, such as chromatography, that require bulky and
sophisticated equipment. In this review, we evaluate the potential to use MIPs
combined with thermal read-out for the detection of low-weight organic molecules.
We discuss thermal methods to study MIP-template complexation and to determine
neurotransmitters concentrations. In particular, we highlight the heat-transfer
method, a recent technique that is straightforward and low cost and requires
minimal instrumentation. Until now, sample preparation involves a 2-step process,
making it time-consuming, and measuring biological samples is difficult owing to
the noise in the signal. Different sample preparation methods are discussed, and
it will be demonstrated how this affects the thermal response. An outlook is
given in novel methods that can simplify and speed up sample preparation.
Finally, we show a novel thermal technique, which is based on the analysis of
transport of thermal waves rather than evaluating the fixed heat-transfer
resistance. Through applying the concept of thermal waves, signal-noise ratio is
significantly increased, which results in lower detection limits and has
potential for the study of biological samples.
PMID- 27611484
TI - Enhancement of Ocular In Situ Gelling Properties of Low Acyl Gellan Gum by Use of
Ion Exchange.
AB - PURPOSE: The purpose of this study was to determine if the addition of calcium
gluconate to gellan solution results in a stronger gel structure on initial
exposure to tear fluid due to the displacement of calcium from the gluconate ion
by tear monovalent cations (Na+, K+). METHODS: Test solutions of gellan and
gellan-calcium gluconate were mixed thoroughly with simulated tear fluid (STF) at
a 5:1 ratio. The resulting gel was measured for viscosity at 32 degrees C-36
degrees C. RESULTS: The addition of optimized amounts of calcium gluconate to
gellan formulations resulted in gellan-calcium gluconate-STF gels of higher
strength (statistically significant) than when gellan alone was mixed with STF.
Gellan experimental preparations demonstrated thixotropic behavior both before
and after addition of STF. CONCLUSIONS: It appears possible to enhance the
initial in situ gel-forming properties of gellan by adding a divalent cation
bound to an ion exchange molecule or resin. Optimal amounts of
polyvinylpyrrolidone (PVP) appear to be effective in slowing timolol release when
added to gellan and calcium gluconate solutions.
PMID- 27611485
TI - Registered nurses' clinical reasoning skills and reasoning process: A think-aloud
study.
AB - BACKGROUND: As complex chronic diseases are increasing, nurses' prompt and
accurate clinical reasoning skills are essential. However, little is known about
the reasoning skills of registered nurses. OBJECTIVE: This study aimed to
determine how registered nurses use their clinical reasoning skills and to
identify how the reasoning process proceeds in the complex clinical situation of
hospital setting. DESIGN: A qualitative exploratory design was used with a think
aloud method. METHODS: A total of 13 registered nurses (mean years of
experience=11.4) participated in the study, solving an ill-structured clinical
problem based on complex chronic patients cases in a hospital setting. Data were
analyzed using deductive content analysis. RESULTS: Findings showed that the
registered nurses used a variety of clinical reasoning skills. The most commonly
used skill was 'checking accuracy and reliability.' The reasoning process of
registered nurses covered assessment, analysis, diagnosis,
planning/implementation, and evaluation phase. CONCLUSIONS: It is critical that
registered nurses apply appropriate clinical reasoning skills in complex clinical
practice. The main focus of registered nurses' reasoning in this study was
assessing a patient's health problem, and their reasoning process was cyclic,
rather than linear. There is a need for educational strategy development to
enhance registered nurses' competency in determining appropriate interventions in
a timely and accurate fashion.
PMID- 27611486
TI - Variability of lysozyme and lactoferrin bioactive protein concentrations in
equine milk in relation to LYZ and LTF gene polymorphisms and expression.
AB - BACKGROUND: Equine milk is considered to be an interesting product for human
nutrition, mainly owing to its low allergenicity and significant amounts of
bioactive proteins, including lysozyme (LYZ) and lactoferrin (LTF). The present
study assessed the effect of genetic factors on LYZ and LTF concentration
variability in mare's milk. RESULTS: Significant effects of horse breed and
lactation stage on milk LYZ and LTF contents were observed. The highest level of
LTF and the lowest concentration of LYZ were recorded for the Polish Warmblood
Horse breed. The highest amounts of both proteins were found for the earliest
investigated time point of lactation (5th week). Altogether 13 (nine novel)
polymorphisms were found in the 5'-flanking regions of both genes, but they
showed no significant relationship with milk LYZ and LTF contents. Several
associations were found between selected SNPs and the LYZ gene relative
transcript level. CONCLUSION: While the present study indicated the existence of
intra- and interbreed variability of LYZ and LTF contents in mare's milk, this
variation is rather unrelated to the 5'-flanking variants of genes encoding both
proteins. This study is a good introduction for broader investigations focused on
the genetic background for variability of bioactive protein contents in mare's
milk. (c) 2016 Society of Chemical Industry.
PMID- 27611487
TI - Predicting Early Rapid Response Team Activation in Patients Admitted From the
Emergency Department: The PeRRT Score.
AB - OBJECTIVES: Rapid response teams (RRTs) respond to signs of deterioration to
avoid morbidity and mortality. Early RRT activation (eRRT) in patients admitted
from the emergency department (ED) is associated with significantly increased
mortality. Predicting these events may represent an opportunity to identify
patients who would benefit from further resuscitation, aid disposition decision
making, or improve communication between ED and inpatient providers. We aimed to
create a clinical prediction instrument to quantify the risk of eRRT. METHODS: We
performed an observational cohort study of patients admitted to a non-intensive
care unit (ICU) setting who triggered eRRT from January 2009 to December of 2012
compared to those who did not trigger eRRT. Age, sex, ED vital sign measurements,
and final ED diagnosis by ICD-9 code were evaluated in a multivariable logistic
regression model. The performance of prediction models was assessed using
discrimination summarized by area under a receiver operating curve (AUC) and
calibration with the Hosmer and Lemeshow goodness-of-fit test. The final model
was used to create a simplified scoring system. RESULTS: The eRRT group consisted
of 474 patients who were compared to 2,575 patients in the reference group. Age
and sex did not add significant discrimination to the model and were eliminated
from the simplified, final model. This model, which included vital signs and
diagnosis category, was found to have an AUC of 0.754 (95% confidence interval
[CI] = 0.730 to 0.778) and was used to create a simplified scoring system. The
odds ratio for the association of a 1-unit increase in risk score with eRRT was
1.37 (95% CI = 1.32 to 1.41; p < 0.001). When internally validated, the score was
found to have an AUC of 0.759 (95% CI = 0.735 to 0.753). Calculated scores ranged
from -3 to 18, which corresponded to predicted probabilities of eRRT ranging from
5.1% to 72.2%. CONCLUSIONS: In summary, the PeRRT score is a simple tool that can
be referenced by emergency providers at the bedside to quantify the risk of early
RRT activation and potential deterioration, helping to answer the question, "How
likely is my patient to trigger an RRT activation in the next twelve hours?"
Given that patients who trigger eRRT have an elevated risk of morbidity and
mortality, higher scores should result in resuscitative intervention, further
observation in the ED, consideration of ICU admission, or direct enhanced
communication between ED and inpatient providers. A prospective multicenter study
is required to further validate this instrument.
PMID- 27611489
TI - Mechanistic Insights on the Photosensitized Chemistry of a Fatty Acid at the
Air/Water Interface.
AB - Interfaces are ubiquitous in the environment and many atmospheric key processes,
such as gas deposition, aerosol, and cloud formation are, at one stage or
another, strongly impacted by physical and chemical processes occurring at
interfaces. Here, the photoinduced chemistry of an air/water interface coated
with nonanoic acid-a fatty acid surfactant we use as a proxy for chemically
complex natural aqueous surface microlayers-was investigated as a source of
volatile and semivolatile reactive organic species. The carboxylic acid coating
significantly increased the propensity of photosensitizers, chosen to mimic those
observed in real environmental waters, to partition to the interface and enhance
reactivity there. Photochemical formation of functionalized and unsaturated
compounds was systematically observed upon irradiation of these coated surfaces.
The role of a coated interface appears to be critical in providing a concentrated
medium allowing radical-radical reactions to occur in parallel with molecular
oxygen additions. Mechanistic insights are provided from extensive analysis of
products observed in both gas and aqueous phases by online switchable reagent ion
time of flight-mass spectrometry and by off-line ultraperformance liquid
chromatography coupled to a Q Exactive high resolution mass spectrometer through
heated electrospray ionization, respectively.
PMID- 27611491
TI - Capillary electrophoresis in the analysis of biologically important thiols.
AB - In this review article, CE methods for analysis of biologically important thiols
are overviewed. The article covers the period from the previously published
comprehensive review in 2004 until mid-2016, with emphasis on various detection
modes, novel approaches for sample preconcentration, and applications in clinical
practice. The most commonly used detection methods, such as conductometry or
absorbance detection, although universally applicable and available in most
commercial instruments have low sensitivity and have only limited use in thiol
analysis. Amperometric and MS detection are more sensitive and have their steady
place in thiol analysis, although the mainstay remains CE with LIF detection,
reaching nanomolar concentration sensitivities for most of the thiols. Novel
probes for CE-LIF have been developed and tested. The preconcentration approaches
using modified gold nanoparticles reaching excellent sensitivities in the
picomolar range and various sample stacking methods are also reviewed. Finally,
significant clinical applications of the developed methods are discussed with
critical insights into the future of CE analysis of thiols.
PMID- 27611492
TI - Dynamics of ultrasonic additive manufacturing.
AB - Ultrasonic additive manufacturing (UAM) is a solid-state technology for joining
similar and dissimilar metal foils near room temperature by scrubbing them
together with ultrasonic vibrations under pressure. Structural dynamics of the
welding assembly and work piece influence how energy is transferred during the
process and ultimately, part quality. To understand the effect of structural
dynamics during UAM, a linear time-invariant model is proposed to relate the
inputs of shear force and electric current to resultant welder velocity and
voltage. Measured frequency response and operating performance of the welder
under no load is used to identify model parameters. Using this model and in-situ
measurements, shear force and welder efficiency are estimated to be near 2000N
and 80% when welding Al 6061-H18 weld foil, respectively. Shear force and welder
efficiency have never been estimated before in UAM. The influence of processing
conditions, i.e., welder amplitude, normal force, and weld speed, on shear force
and welder efficiency are investigated. Welder velocity was found to strongly
influence the shear force magnitude and efficiency while normal force and weld
speed showed little to no influence. The proposed model is used to describe high
frequency harmonic content in the velocity response of the welder during welding
operations and coupling of the UAM build with the welder.
PMID- 27611488
TI - Identification of Four Novel Loci in Asthma in European American and African
American Populations.
AB - RATIONALE: Despite significant advances in knowledge of the genetic architecture
of asthma, specific contributors to the variability in the burden between
populations remain uncovered. OBJECTIVES: To identify additional genetic
susceptibility factors of asthma in European American and African American
populations. METHODS: A phenotyping algorithm mining electronic medical records
was developed and validated to recruit cases with asthma and control subjects
from the Electronic Medical Records and Genomics network. Genome-wide association
analyses were performed in pediatric and adult asthma cases and control subjects
with European American and African American ancestry followed by metaanalysis.
Nominally significant results were reanalyzed conditioning on allergy status.
MEASUREMENTS AND MAIN RESULTS: The validation of the algorithm yielded an average
of 95.8% positive predictive values for both cases and control subjects. The
algorithm accrued 21,644 subjects (65.83% European American and 34.17% African
American). We identified four novel population-specific associations with asthma
after metaanalyses: loci 6p21.31, 9p21.2, and 10q21.3 in the European American
population, and the PTGES gene in African Americans. TEK at 9p21.2, which encodes
TIE2, has been shown to be involved in remodeling the airway wall in asthma, and
the association remained significant after conditioning by allergy. PTGES, which
encodes the prostaglandin E synthase, has also been linked to asthma, where
deficient prostaglandin E2 synthesis has been associated with airway remodeling.
CONCLUSIONS: This study adds to understanding of the genetic architecture of
asthma in European Americans and African Americans and reinforces the need to
study populations of diverse ethnic backgrounds to identify shared and unique
genetic predictors of asthma.
PMID- 27611493
TI - Finite element analysis of the Rayleigh wave scattering in isotropic bi-material
wedge structures.
AB - The numerical study is performed of the harmonic Rayleigh wave scattering in a
composite structure constructed from two elastically isotropic 90 degrees
wedges. These wedges are in contact along one pair of their faces. It is assumed
that either the perfectly sliding contact or the perfectly rigid one is realized.
The other pair of faces forms a plane border between the resulting bi-material
wedge and the exterior half-infinite space occupied by vacuum. The finite element
method is used. The perfectly matched layer spatially confines the computational
domain. The dependences of the reflection and transmission coefficients of the
Rayleigh wave on the angle of incidence, the Poisson ratio and the type of
contact are obtained and analyzed for different combinations of materials. The
behavior of the coefficient of the Rayleigh wave conversion into the interfacial
wave which may exist on the internal boundary of the structure is also
investigated. A number of relations between the coefficients of conversion are
derived from symmetry considerations for structures with sliding contact and
composed of identical isotropic materials.
PMID- 27611494
TI - Reliability of Pain Measurements Using Computerized Cuff Algometry: A DoloCuff
Reliability and Agreement Study.
AB - INTRODUCTION: Computerized pneumatic cuff pressure algometry (CPA) using the
DoloCuff is a new method for pain assessment. Intra- and inter-rater
reliabilities have not yet been established. Our aim was to examine the inter-
and intrarater reliabilities of DoloCuff measures in healthy subjects. METHODS:
Twenty healthy subjects (ages 20 to 29 years) were assessed three times at 24
hour intervals by two trained raters. Inter-rater reliability was established
based on the first and second assessments, whereas intrarater reliability was
based on the second and third assessments. Subjects were randomized 1:1 to first
assessment at either rater 1 or rater 2. The variables of interest were pressure
pain threshold (PT), pressure pain tolerance (PTol), and temporal summation index
(TSI). Reliability was estimated by a two-way mixed intraclass correlation
coefficient (ICC) absolute agreement analysis. Reliability was considered
excellent if ICC > 0.75, fair to good if 0.4 < ICC < 0.75, and poor if ICC < 0.4.
Bias and random errors between raters and assessments were evaluated using 95%
confidence interval (CI) and Bland-Altman plots. RESULTS: Inter-rater reliability
for PT, PTol, and TSI was 0.88 (95% CI: 0.69 to 0.95), 0.86 (95% CI: 0.65 to
0.95), and 0.81 (95% CI: 0.42 to 0.94), respectively. The intrarater reliability
for PT, PTol, and TSI was 0.81 (95% CI: 0.53 to 0.92), 0.89 (95% CI: 0.74 to
0.96), and 0.75 (95% CI: 0.28 to 0.91), respectively. CONCLUSION: Inter-rater
reliability was excellent for PT, PTol, and TSI. Similarly, the intrarater
reliability for PT and PTol was excellent, while borderline excellent/good for
TSI. Therefore, the DoloCuff can be used to obtain reliable measures of pressure
pain parameters in healthy subjects.
PMID- 27611496
TI - A whole-molecule immunocapture LC-MS approach for the in vivo quantitation of
biotherapeutics.
AB - AIM: Large-molecule biotherapeutic quantitation in vivo by LC-MS has
traditionally relied on enzymatic digestion followed by quantitation of a
'surrogate peptide' to infer whole-molecule concentration. MS methods presented
here measure the whole molecule and provide a platform to better understand the
various circulating drug forms by allowing for variant quantitation. RESULTS: An
immunocapture LC-MS method for quantitation of a biotherapeutic monoclonal
antibody from human plasma is presented. Sensitivity, precision and accuracy for
each molecular portion are presented along with an example of glycoform variant
quantitation. CONCLUSION: The method is presented as a basic platform to be
further developed for Good Practice (GxP) applications, critical quality
attribute analysis or general understanding of molecular forms present as
required for the wide range of drug development processes.
PMID- 27611495
TI - Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Associated with
Risk of Pulmonary Embolism.
AB - PURPOSE: We conducted a cohort study to clarify this relationship between asthma
chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and
pulmonary embolism (PE). METHODS: From the National Health Insurance Research
Database of Taiwan, we identified patients who had a diagnosis of asthma and a
diagnosis of COPD (defined as ACOS) and concurrent treatment between January 1999
and December 2009 (ACOS cohort: n = 14,150; non-ACOS cohort: n = 55,876). Cox
proportional hazards regression analysis was performed to determine the adjusted
hazard ratios (aHRs) for PE of the ACOS cohort compared with the non-ACOS cohort.
RESULTS: Comparing the ACOS cohort with the non-ACOS cohort, the aHR of PE was
2.08 (95% confidence intervals [CIs]: 1.56-2.76). The risk of PE was higher in
ACOS cohort than non-ACOS cohort, regardless of age, sex, comorbidity, inhaled
corticosteroids (ICSs) and oral steroids (OSs) used. For ages ranging from 20 to
65 years, the aHR of PE was 2.53 (95% CI: 1.44-4.44) in the ACOS cohort. ACOS
patients using ICSs (aHR: 1.97, 95% CI: 1.29-3.01) or OSs (aHR: 1.97, 95% CI:
1.46-2.65), the risk of PE was higher than in the non-ACOS cohort. The risk of PE
increased with the number of outpatient visits and hospitalizations necessitated,
ranging from 2.32 (95% CI: 1.54-3.52) in patients having 3-9 visits to 4.20 (95%
CI: 2.74-6.44) for those having >9 visits. CONCLUSIONS: ACOS is associated with
increased risk of PE, particularly patients with a high frequency of AE-even in
young adults or people without comorbidities.
PMID- 27611497
TI - Interactions between depolymerized fucosylated glycosaminoglycan and coagulation
proteases or inhibitors.
AB - Fucosylated glycosaminoglycan (FG) is a structurally novel glycosaminoglycan
derivative, and it has potent anticoagulant activity. Depolymerized FG (dFG) is a
selective factor Xase (FXase, FIXa-FVIIIa complex) inhibitor and it has
antithrombotic action without major bleeding risks. In this study, we report the
effects of dFG-3 (Mw ~14kDa) on the catalysis rates of factor IIa (FIIa), factor
Xa (FXa) and factor IXa (FIXa) inhibition by antithrombin (AT), and the kinetic
of the interactions between coagulation proteases or inhibitors and dFG-3 were
also studied using biolayer interferometry (BLI) technology. We found that dFG-3
had much weaker catalysis activity of coagulation proteases inhibition by AT
compared with heparin (UFH). The binding affinity of AT bound to dFG-3 was lower
than UFH, and the UFH-AT interaction fitted well with biphasic-binding model
while dFG-3-AT interaction was monophasic-binding, suggesting dFG-3 might not
have allosteric activation effect on AT. The results are consistent with AT
independent inhibitory activities of dFG-3. dFG-3 could strongly bind to FIXa
with much higher affinity than UFH, further explained the reason for its potent
FXase inhibitory activity. Additionally, the binding ability of dFG-3 and FIXa
decreased with decreasing molecular, and the fucose side chains and carboxyl
groups of dFG-3 might be required for its high affinity binding with FIXa. Our
data supports further the investigation of dFG-3 as a promising anticoagulant
drug inhibiting the intrinsic FXase by binding to FIXa.
PMID- 27611498
TI - Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by
increasing thrombolysis resistance under shear stress in an in-vitro flow chamber
model.
AB - INTRODUCTION: Despite the proven benefits of thrombolytic therapy with tissue
plasminogen activator (t-PA) for peripheral thromboembolism, perfusion failure
frequently occurs, particularly in arterial circulation. We evaluated how the
modification of fibrinolytic activity affects thrombus formation under flow and
static conditions. MATERIALS AND METHODS: t-PA-treated human whole-blood samples
(n=6) were perfused over a microchip coated with collagen and tissue
thromboplastin at different shear rates, and thrombus formation was quantified by
measuring flow pressure changes. For comparison, rotational thromboelastometry
(ROTEM) was used to evaluate fibrinolytic activity under static conditions.
RESULTS: At a shear rate of 240s-1, t-PA (200-800IU/ml) concentration-dependently
delayed capillary occlusion, whereas at 600s-1, capillary occlusion was
significantly faster and t-PA had limited effects, even at a supra
pharmacological concentration (800IU/ml). In contrast, 200IU/ml t-PA efficiently
prevented clot formation in the ROTEM assay. The combined treatment of blood with
a specific PAI-1 inhibitor (PAI-039) moderately enhanced the efficacy of t-PA,
but only under flow conditions. In addition, 1:1-diluted blood samples of PAI-1
deficient (-/-) mice showed a significant delay of capillary occlusion at 240s-1,
compared with those from wild-type mice (1.55 fold; P<0.001). This delayed
occlusion was reproduced in samples containing platelets from PAI-1-/- and plasma
from wild type, but was not observed by the opposite combination of blood
components. CONCLUSIONS: The present results suggest that the anti-thrombotic
efficacy of t-PA is sensitive to arterial shear flow, and that PAI-1 secreted
from activated platelets plays an essential role in thrombolytic resistance.
PMID- 27611499
TI - Photochromic Terbium Phosphonates with Photomodulated Luminescence and Metal Ion
Sensitive Detection.
AB - Rational selection and modification of rare earth metal centers and photoactive
organic linkers enables designable multiphotofunctionality to come to fruition in
new hybrid coordination polymer materials. By using a viologen-functionalized
diphosphonate linker, two terbium phosphonate compounds (Tb-1 and Tb-2) have been
constructed, which display reversible photochromic reactions in response to UV
light and soft X-ray irradiation. In addition, the photo-induced electron
transfer reaction can modulate the luminescent emission to thus realize
photoluminescence switching behavior. Furthermore, both terbium phosphonates can
serve as highly sensitive sensors to probe Cu2+ in solution through their
luminescence. Thus, they represent the first photochromic examples of lanthanide
phosphonate-based materials with photomodulated luminescence and sensitive
detection of metal ions.
PMID- 27611500
TI - Gross Osteology, Radiographic and Computed Tomographic Morphology of the Axial
Skeleton of the Nine-Banded Armadillo (Dasypus novemcinctus).
AB - This study used 20 nine-banded armadillo, four in vivo and 16 cadavers, to
describe the osteoarticular anatomy of the axial skeleton by means of digital
radiography and computed tomography. Vertebral formula obtained in this sample
specimens was seven cervical, 10 thoracic, five lumbar, nine vertebrae related to
the synsacrum and 20-27 free caudal vertebrae. Peculiar features of this species
were noted as the presence of xenarthrous processes in the caudal thoracic
vertebra to the last lumbar vertebra, with prominent mammillary processes in the
thoracolumbar segment, fused cervical vertebra from the second to fourth vertebra
and the presence of synsacrum related to sacral and caudal vertebra fused to the
pelvis. They are homodont animals presenting only molariform teeth with formula
of 8/8, totalling 32 teeth. There was no complexity in the execution of
radiographic and tomographic examinations, concluding that execution can be
carried out in nine-banded armadillos during the clinical routine for wild
animals.
PMID- 27611501
TI - Distinct Short-Range Order Is Inherent to Small Amorphous Calcium Carbonate
Clusters (<2 nm).
AB - Amorphous intermediate phases are vital precursors in the crystallization of many
biogenic minerals. While inherent short-range orders have been found in amorphous
calcium carbonates (ACCs) relating to different crystalline forms, it has never
been clarified experimentally whether such orders already exist in very small
clusters less than 2 nm in size. Here, we studied the stability and structure of
10,12-pentacosadiynoic acid (PCDA) protected ACC clusters with a core size of ca.
1.4 nm consisting of only seven CaCO3 units. Ligand concentration and structure
are shown to be key factors in stabilizing the ACC clusters. More importantly,
even in such small CaCO3 entities, a proto-calcite short-range order can be
identified but with a relatively high degree of disorder that arises from the
very small size of the CaCO3 core. Our findings support the notion of a
structural link between prenucleation clusters, amorphous intermediates, and
final crystalline polymorphs, which appears central to the understanding of
polymorph selection.
PMID- 27611505
TI - Abstractband anlasslich des 26. Deutschen Hautkrebskongresses (ADO-Jahrestagung),
22. bis 24. September 2016 in Dresden.
PMID- 27611502
TI - Different strategies of metabolic regulation in cyanobacteria: from
transcriptional to biochemical control.
AB - Cyanobacteria Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803 show
similar changes in the metabolic response to changed CO2 conditions but exhibit
significant differences at the transcriptomic level. This study employs a systems
biology approach to investigate the difference in metabolic regulation of
Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803. Presented multi-level
kinetic model for Synechocystis sp. PCC 6803 is a new approach integrating and
analysing metabolomic, transcriptomic and fluxomics data obtained under high and
ambient CO2 levels. Modelling analysis revealed that higher number of different
isozymes in Synechocystis 6803 improves homeostatic stability of several
metabolites, especially 3PGA by 275%, against changes in gene expression,
compared to Synechococcus sp. PCC 7942. Furthermore, both cyanobacteria have the
same amount of phosphoglycerate mutases but Synechocystis 6803 exhibits only ~20%
differences in their mRNA levels after shifts from high to ambient CO2 level, in
comparison to ~500% differences in the case of Synechococcus sp. PCC 7942. These
and other data imply that the biochemical control dominates over transcriptional
regulation in Synechocystis 6803 to acclimate central carbon metabolism in the
environment of variable inorganic carbon availability without extra cost carried
by large changes in the proteome.
PMID- 27611504
TI - Marine environment pollution: The contribution of mass spectrometry to the study
of seawater.
AB - The study of marine pollution has been traditionally addressed to persistent
chemicals, generally known as priority pollutants; a current trend in
environmental analysis is a shift toward "emerging pollutants," defined as newly
identified or previously unrecognized contaminants. The present review is focused
on the peculiar contribution of mass spectrometry (MS) to the study of pollutants
in the seawater compartment. The work is organized in five paragraphs where the
most relevant groups of pollutants, both "classical" and "emerging," are
presented and discussed, highlighting the relative data obtained by the means of
different MS techniques. The hyphenation of MS and separative techniques,
together with the development of different ion sources, makes MS and tandem MS
the analytical tool of choice for the determination of trace organic contaminants
in seawater. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:492-512, 2018.
PMID- 27611506
TI - Simulation-Based Training May Improve Resident Skill in Ultrasound-Guided Biopsy.
AB - OBJECTIVE: The purpose of this study was to determine whether simulation-based
training can improve resident performance in ultrasound-guided biopsy. SUBJECTS
AND METHODS: Forty radiology residents from a single academic institution
enrolled in the study. Each resident performed an initial biopsy on an abdominal
imaging phantom using direct ultrasound guidance. Twenty of the residents
underwent a 30-minute training session with the phantom device, and 20 residents
received no additional training. The residents performed a repeat biopsy of the
same lesion and were graded on overall procedure time, number of skin surface
punctures, number of gross needle adjustments, and subjective performance as
determined by a blinded grader. RESULTS: Residents who participated in the
training had a statistically significant 92.3-second reduction in procedure time
(68% improvement, p = 0.01), 1.1 reduction in number of skin punctures per biopsy
(50% improvement, p = 0.05), 2.5 reduction in number of needle adjustments (66%
improvement, p = 0.04), and an increase of 0.85 points in score on a 5-point
Likert grading scale (23% improvement, p < 0.01). Residents who did not receive
any additional training did not improve in any performance metric. CONCLUSION:
Simulation-based training improves overall procedure time, number of skin
punctures and needle adjustments, and subjective performance.
PMID- 27611507
TI - Idiopathic tumoral calcinosis-like lesion in the lower cervical spine causing
acute central cord syndrome: case report.
AB - A 57-year-old male presented with recurrent falls, bilateral lower-limb
paresthesia, and severe neck pain. Imaging revealed a mass compressing his spinal
cord. He was admitted for further workup for spinal cord compression. Within 24
hours of admission, he developed upper-extremity weakness while maintaining lower
extremity function. He underwent urgent decompression of his spinal cord. During
exposure, a white, creamy odorless substance was noted. This same substance was
found under pressure within the spinal canal. The mass was grossly removed, and
the patient's weakness improved postoperatively. Based on the clinical picture,
intraoperative presentation, and final histological examination, idiopathic
tumoral calcinosis-like lesion was considered as the most appropriate diagnosis.
PMID- 27611508
TI - The effect of posterior polyester tethers on the biomechanics of proximal
junctional kyphosis: a finite element analysis.
AB - OBJECTIVE Proximal junctional kyphosis (PJK) remains problematic following
multilevel instrumented spine surgery. Previous biomechanical studies indicate
that providing less rigid fixation at the cranial aspect of a long posterior
instrumented construct, via transition rods or hooks at the upper instrumented
vertebra (UIV), may provide a gradual transition to normal motion and prevent
PJK. The purpose of this study was to evaluate the ability of posterior anchored
polyethylene tethers to distribute proximal motion segment stiffness in long
instrumented spine constructs. METHODS A finite element model of a T7-L5 spine
segment was created to evaluate range of motion (ROM), intradiscal pressure,
pedicle screw loads, and forces in the posterior ligament complex within and
adjacent to the proximal terminus of an instrumented spine construct. Six models
were tested: 1) intact spine; 2) bilateral, segmental pedicle screws (PS) at all
levels from T-11 through L-5; 3) bilateral pedicle screws from T-12 to L-5 and
transverse process hooks (TPH) at T-11 (the UIV); 4) pedicle screws from T-11 to
L5 and 1-level tethers from T-10 to T-11 (TE-UIV+1); 5) pedicle screws from T-11
to L-5 and 2-level tethers from T-9 to T-11 (TE-UIV+2); and 6) pedicle screws and
3-level tethers from T-8 to T-11 (TE-UIV+3). RESULTS Proximal-segment range of
motion (ROM) for the PS construct increased from 16% at UIV-1 to 91% at UIV.
Proximal-segment ROM for the TPH construct increased from 27% at UIV-1 to 92% at
UIV. Posterior tether constructs distributed ROM at the UIV and cranial adjacent
segments most effectively; ROM for TE-UIV+1 was 14% of the intact model at UIV-1,
76% at UIV, and 98% at UIV+1. ROM for TE-UIV+2 was 10% at UIV-1, 51% at UIV, 69%
at UIV+1, and 97% at UIV+2. ROM for TE-UIV+3 was 7% at UIV-1, 33% at UIV, 45% at
UIV+1, and 64% at UIV+2. Proximal segment intradiscal pressures, pedicle screw
loads, and ligament forces in the posterior ligament complex were progressively
reduced with increasing number of posterior tethers used. CONCLUSIONS Finite
element analysis of long instrumented spine constructs demonstrated that
posterior tethers created a more gradual transition in ROM and adjacent-segment
stress from the instrumented to the noninstrumented spine compared with all PS
and TPH constructs. Posterior tethers may limit the biomechanical risk factor for
PJK; however, further clinical research is needed to evaluate clinical efficacy.
PMID- 27611509
TI - An avoidable adverse drug reaction: Nicolau syndrome.
PMID- 27611563
TI - Antibiotic Potency against E. coli Is Enhanced by Channel-Forming Alkyl Lariat
Ethers.
AB - Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to
significantly enhance the potency of rifampicin and tetracycline, but not
erythromycin and kanamycin, against the non-pathogenic DH5alpha and K-12 strains
of Escherichia coli when administered at levels below their minimum inhibitory
concentrations (MICs). The enhancements in antibiotic potency observed for the
lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli,
the antibiotic, and the lengths of the alkyl chains attached at the macroring
nitrogen atoms. The dialkyl lariat ethers, previously thought to only be cation
carriers, formed well-behaved, ion-conducting pores in soybean asolectin
membranes, as judged by planar bilayer conductance measurements. The ability of
lariat ethers to form stable pores, which appeared to be aggregated, depended in
part on alkyl chain length and in part on the composition of the bilayer membrane
in which they were studied.
PMID- 27611565
TI - Validation of a candidate causative mutation for white spotting in donkeys.
PMID- 27611564
TI - Plasmonic twinned silver nanoparticles with molecular precision.
AB - Determining the structures of nanoparticles at atomic resolution is vital to
understand their structure-property correlations. Large metal nanoparticles with
core diameter beyond 2 nm have, to date, eluded characterization by single
crystal X-ray analysis. Here we report the chemical syntheses and structures of
two giant thiolated Ag nanoparticles containing 136 and 374 Ag atoms (that is, up
to 3 nm core diameter). As the largest thiolated metal nanoparticles
crystallographically determined so far, these Ag nanoparticles enter the truly
metallic regime with the emergence of surface plasmon resonance. As miniatures of
fivefold twinned nanostructures, these structures demonstrate a subtle distortion
within fivefold twinned nanostructures of face-centred cubic metals. The Ag
nanoparticles reported in this work serve as excellent models to understand the
detailed structure distortion within twinned metal nanostructures and also how
silver nanoparticles can span from the molecular to the metallic regime.
PMID- 27611566
TI - Gold nanoparticles synthesized using Panax ginseng leaves suppress inflammatory -
mediators production via blockade of NF-kappaB activation in macrophages.
AB - In the present study, we report that Gold nanoparticles (AuNPs) synthesized using
the leaf extract of Panax ginseng Meyer (P.g AuNPs) exert anti-inflammatory
effects through inhibition of downstream NF-kappaB activation in macrophages. We
found that P.g AuNPs reduced the expression of the inflammatory mediators
including nitric oxide (NO), prostaglandin E2 (PEG2), interleukin (IL)-6, tumor
necrosis factor-alpha (TNF-alpha) was attenuated by P.g AuNPs. Furthermore, P.g
AuNPs suppressed lipopolysaccharide (LPS)-induced activation of NF-kappaB
signaling pathway via p38 mitogen-activated protein kinase (MAPK) in RAW 264.7
cells. Taken together, our results suggest that P.g AuNPs can be utilized as a
novel therapeutic agent for the prevention and cure of inflammation.
PMID- 27611568
TI - Coping with workplace minority stress: Associations between dyadic coping and
anxiety among women in same-sex relationships.
AB - Sexual minorities are exposed to stressors in the workplace (workplace minority
stress), which can be detrimental for well-being (e.g., levels of anxiety). The
present study examined whether a particular set of relationship processes, dyadic
coping, served to moderate the association between workplace minority stress and
symptoms of anxiety. Using a dyadic sample of 64 female same-sex couples, we
found that partner problem-focused supportive dyadic coping (DC) and emotion
focused supportive DC (marginally) buffered, whereas partner delegated DC and
negative DC did not moderate, the association between workplace minority stress
and symptoms of anxiety. Implications for relationship researchers and mental
health practitioners are discussed.
PMID- 27611567
TI - Calcineurin Targets Involved in Stress Survival and Fungal Virulence.
AB - Calcineurin governs stress survival, sexual differentiation, and virulence of the
human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by
increased Ca2+ levels caused by stress, and transduces signals by
dephosphorylating protein substrates. Herein, we identified and characterized
calcineurin substrates in C. neoformans by employing phosphoproteomic TiO2
enrichment and quantitative mass spectrometry. The identified targets include the
transactivator Crz1 as well as novel substrates whose functions are linked to P
bodies/stress granules (PBs/SGs) and mRNA translation and decay, such as Pbp1 and
Puf4. We show that Crz1 is a bona fide calcineurin substrate, and Crz1
localization and transcriptional activity are controlled by calcineurin. We
previously demonstrated that thermal and other stresses trigger calcineurin
localization to PBs/SGs. Several calcineurin targets localized to PBs/SGs,
including Puf4 and Pbp1, contribute to stress resistance and virulence
individually or in conjunction with Crz1. Moreover, Pbp1 is also required for
sexual development. Genetic epistasis analysis revealed that Crz1 and the novel
targets Lhp1, Puf4, and Pbp1 function in a branched calcineurin pathway that
orchestrates stress survival and virulence. These findings support a model
whereby calcineurin controls stress and virulence, at the transcriptional level
via Crz1, and post-transcriptionally by localizing to PBs/SGs and acting on
targets involved in mRNA metabolism. The calcineurin targets identified in this
study share little overlap with known calcineurin substrates, with the exception
of Crz1. In particular, the mRNA binding proteins and PBs/SGs residents comprise
a cohort of novel calcineurin targets that have not been previously linked to
calcineurin in mammals or in Saccharomyces cerevisiae. This study suggests either
extensive evolutionary rewiring of the calcineurin pathway, or alternatively that
these novel calcineurin targets have yet to be characterized as calcineurin
targets in other organisms. These findings further highlight C. neoformans as an
outstanding model to define calcineurin-responsive virulence networks as targets
for antifungal therapy.
PMID- 27611570
TI - Novel developments in stress cardiomyopathy: From pathophysiology to prognosis.
AB - Stress cardiomyopathy (SC) is characterized by transient left ventricular (LV)
wall motion abnormalities typically involving the apex with preserved basal
contractility, chest discomfort, ST-T ischemic changes and elevated cardiac
markers with normal or non-flow limiting coronary artery lesions. It represents
an important differential diagnosis of Acute Coronary Syndromes caused by
atherosclerotic vessel occlusion; most commonly, Tako-tsubo occurs in
postmenopausal women after physical or emotional stress. While the exact
mechanism of SC remains controversial, various hypotheses have been suggested
concerning the vascular, central nervous and endocrine system participation where
catecholamines, particularly epinephrine, seem to play a major role. Hormonal,
genetic and psychiatric conditions may also define the risk of susceptibility in
some groups affected by SC. Long-term survival data are limited with mortality
occurring predominantly in the first year after diagnosis usually related to non
cardiac illnesses. Echocardiography promises to become a useful tool to correctly
identify SC patients at high risk for complications.
PMID- 27611569
TI - Epidemiology and outcomes of out-of-hospital cardiac arrest in Qatar: A
nationwide observational study.
AB - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) studies from the Middle East
and Asian region are limited. This study describes the epidemiology, emergency
health services, and outcomes of OHCA in Qatar. METHODS: This was a prospective
nationwide population-based observational study on OHCA patients in Qatar
according to Utstein style guidelines, from June 2012 to May 2013. Data was
collected from various sources; the national emergency medical service, 4
emergency departments, and 8 public hospitals. RESULTS: The annual crude
incidence of presumed cardiac OHCA attended by EMS was 23.5 per 100,000. The age
sex standardized incidence was 87.8 per 100,000 population. Of the 447 OHCA
patients included in the final analysis, most were male (n=360, 80.5%) with
median age of 51years (IQR=39-66). Frequently observed nationalities were Qatari
(n=89, 19.9%), Indian (n=74, 16.6%) and Nepalese (n=52, 11.6%). Bystander
cardiopulmonary resuscitation (CPR) was carried out in 92 (20.6%) OHCA patients.
Survival rate was 8.1% (n=36) and multivariable logistic regression indicated
that initial shockable rhythm (OR 13.4, 95% CI 5.4-33.3, p=0.001) was associated
with higher odds of survival while male gender (OR 0.27, 95% CI 0.1-0.8, p=0.01)
and advanced cardiac life support (ACLS) (OR 0.15, 95% CI 0.04-0.5, p=0.02) were
associated with lower odds of survival. CONCLUSIONS: Standardized incidence and
survival rates were comparable to Western countries. Although expatriates
comprise more than 80% of the population, Qataris contributed 20% of the total
cardiac arrests observed. There are significant opportunities to improve
outcomes, including community-based CPR and defibrillation training.
PMID- 27611572
TI - Transcriptome Profile Analysis of Breast Muscle Tissues from High or Low Levels
of Atmospheric Ammonia Exposed Broilers (Gallus gallus).
AB - Atmospheric ammonia is a common problem in poultry industry. High concentrations
of aerial ammonia cause great harm to broilers' health and production. For the
consideration of human health, the limit exposure concentration of ammonia in
houses is set at 25 ppm. Previous reports have shown that 25 ppm is still
detrimental to livestock, especially the gastrointestinal tract and respiratory
tract, but the negative relationship between ammonia exposure and the tissue of
breast muscle of broilers is still unknown. In the present study, 25 ppm ammonia
in poultry houses was found to lower slaughter performance and breast yield.
Then, high-throughput RNA sequencing was utilized to identify differentially
expressed genes in breast muscle of broiler chickens exposed to high (25 ppm) or
low (3 ppm) levels of atmospheric ammonia. The transcriptome analysis showed that
163 genes (fold change >= 2 or <= 0.5; P-value < 0.05) were differentially
expressed between Ammonia25 (treatment group) and Ammonia3 (control group),
including 96 down-regulated and 67 up-regulated genes. qRT-PCR analysis validated
the transcriptomic results of RNA sequencing. Gene Ontology (GO) functional
annotation analysis revealed potential genes, processes and pathways with
putative involvement in growth and development inhibition of breast muscle in
broilers caused by aerial ammonia exposure. This study facilitates understanding
of the genetic architecture of the chicken breast muscle transcriptome, and has
identified candidate genes for breast muscle response to atmospheric ammonia
exposure.
PMID- 27611571
TI - Diversity in a Polymicrobial Community Revealed by Analysis of Viromes,
Endolysins and CRISPR Spacers.
AB - The polymicrobial biofilm communities in Mushroom and Octopus Spring in
Yellowstone National Park (YNP) are well characterized, yet little is known about
the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2-13),
Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1,
contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage
predators. To analyze phage populations from Octopus Spring biofilms, we
sequenced a viral enriched fraction. To assemble and analyze phage metagenomic
data, we developed a custom module, VIRITAS, implemented within the MetAMOS
framework. This module bins contigs into groups based on tetranucleotide
frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this
pipeline we were able to assemble phage sequences into contigs and bin them into
three clusters that corroborated with their potential host range. The virome
contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a
recognizable Pfam domain while the rest were hypothetical. Of the recognized
domains with CRISPR spacer matches, was the phage endolysin used by lytic phage
to disrupt cells. Analysis of the endolysins present in the thermophilic
cyanophage contigs revealed a subset of characterized endolysins as well as a
Glyco_hydro_108 (PF05838) domain not previously associated with sequenced
cyanophages. A search for CRISPR spacer matches to all identified phage
endolysins demonstrated that a majority of endolysin domains were targets. This
strategy provides a general way to link host and phage as endolysins are known to
be widely distributed in bacteriophage. Endolysins can also provide information
about host cell wall composition and have the additional potential to be used as
targets for novel therapeutics.
PMID- 27611573
TI - One-Pot Three-Component Synthesis of 2-Imino-1,3-Thiazolines on Soluble Ionic
Liquid Support.
AB - An efficient one-pot, three-component synthesis of 2-imino-1,3-thiazolidines and
2-imino-1,3-thiazolines using ionic liquid-tethered 2-aminobenzimidazoles was
reported. The protocol includes reaction of ionic liquid attached 2
aminobenzimidazoles with isothiocyanates to afford isothioureas, followed by its
base induced inter and intramolecular nucleophilic displacement reactions with
1,2-dichloroethane (EDC) which results in thiazolidine ring formation. In the
next to the last step, the ionic liquid support was removed by methanolysis to
deliver 2-imino-1,3-thiazolidines, which were sequentially oxidized with
manganese(III) triacetate to yield 2-imino-1,3-thiazolines. The salient feature
of this method is the use of 1,2-dichloroethane as a synthetic equivalent for
alpha-haloketone to avoid the use of toxic halogenating reagents.
PMID- 27611575
TI - Wolbachia Has Two Different Localization Patterns in Whitefly Bemisia tabaci
AsiaII7 Species.
AB - The whitefly Bemisia tabaci is a cosmopolitan insect species complex that harbors
the obligate primary symbiont Portiera aleyrodidarum and several facultative
secondary symbionts including Wolbachia, which have diverse influences on the
host biology. Here, for the first time, we revealed two different localization
patterns of Wolbachia present in the immature and adult stages of B. tabaci
AsiaII7 cryptic species. In the confined pattern, Wolbachia was restricted to the
bacteriocytes, while in the scattered pattern Wolbachia localized in the
bacteriocytes, haemolymph and other organs simultaneously. Our results further
indicated that, the proportion of B. tabaci AsiaII7 individuals with scattered
Wolbachia were significantly lower than that of confined Wolbachia, and the
distribution patterns of Wolbachia were not associated with the developmental
stage or sex of whitefly host. This study will provide a new insight into the
various transmission routes of Wolbachia in different whitefly species.
PMID- 27611574
TI - Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor
Deficiency-Mediated Colitis in SJL Mice.
AB - Theiler's murine encephalomyelitis virus (TMEV)-infection is a widely used animal
model for studying demyelinating disorders, including multiple sclerosis (MS).
The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune
responses and critically controls immune homeostasis in infectious and autoimmune
disorders. In order to investigate the effect of signaling via Interleukin-10
receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice
were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of
the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization
leads to progressive colitis with a reduction in Foxp3+ regulatory T cells and
increased numbers of CD8+CD44+ memory T cells as well as activated CD4+CD69+ and
CD8+CD69+ T cells in uninfected mice. (ii) Concurrent acute TMEV-infection
worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered
effects were associated with an enhanced activation of CD4+ T helper cells and
CD8+ cytotoxic T lymphocytes and augmented cytokine expression. By contrast,
(iii) IL-10R neutralization during chronic TMEV-infection was not associated with
enhanced peripheral immunopathology but an increased CD3+ T cell influx in the
spinal cord. IL-10R neutralization causes a breakdown in peripheral immune
tolerance in genetically predisposed mice, which leads to immune-mediated
colitis, resembling inflammatory bowel disease. Hyperactive immune state
following IL-10R blockade is enhanced by central nervous system-restricted viral
infection in a disease phase-dependent manner.
PMID- 27611576
TI - Optimization of Extraction Conditions for Maximal Phenolic, Flavonoid and
Antioxidant Activity from Melaleuca bracteata Leaves Using the Response Surface
Methodology.
AB - Melaleuca bracteata is a yellow-leaved tree belonging to the Melaleuca genus.
Species from this genus are known to be good sources of natural antioxidants, for
example, the "tea tree oil" derived from M. alternifolia is used in food
processing to extend the shelf life of products. In order to determine whether M.
bracteata contains novel natural antioxidants, the components of M. bracteata
ethanol extracts were analyzed by gas chromatography-mass spectrometry. Total
phenolic and flavonoid contents were extracted and the antioxidant activities of
the extracts evaluated. Single-factor experiments, central composite rotatable
design (CCRD) and response surface methodology (RSM) were used to optimize the
extraction conditions for total phenolic content (TPC) and total flavonoid
content (TFC). Ferric reducing power (FRP) and 1,1-Diphenyl-2-picrylhydrazyl
radical (DPPH.) scavenging capacity were used as the evaluation indices of
antioxidant activity. The results showed that the main components of M. bracteata
ethanol extracts are methyl eugenol (86.86%) and trans-cinnamic acid methyl ester
(6.41%). The single-factor experiments revealed that the ethanol concentration is
the key factor determining the TPC, TFC, FRP and DPPH.scavenging capacity. RSM
results indicated that the optimal condition of all four evaluation indices was
achieved by extracting for 3.65 days at 53.26 degrees C in 34.81% ethanol. Under
these conditions, the TPC, TFC, FRP and DPPH.scavenging capacity reached values
of 88.6 +/- 1.3 mg GAE/g DW, 19.4 +/- 0.2 mg RE/g DW, 2.37 +/- 0.01 mM Fe2+/g DW
and 86.0 +/- 0.3%, respectively, which were higher than those of the positive
control, methyl eugenol (FRP 0.97 +/- 0.02 mM, DPPH.scavenging capacity 58.6 +/-
0.7%) at comparable concentrations. Therefore, the extracts of M. bracteata
leaves have higher antioxidant activity, which did not only attributed to the
methyl eugenol. Further research could lead to the development of a potent new
natural antioxidant.
PMID- 27611578
TI - Association between occupational lifting and day-to-day change in low-back pain
intensity based on company records and text messages.
AB - Objective This study aimed to investigate the association between occupational
lifting and day-to-day change in low-back pain (LBP) intensity. Methods Each day
for three consecutive weeks, 95 full-time workers from 51 Danish supermarkets
with frequent occupational lifting replied to daily text messages about LBP
intensity (scale 0-10). Supervisors at the supermarkets provided information
about daily working hours and load (number of different pallets handled) for each
worker during the three weeks. Linear mixed models with repeated measures tested
the association between variables controlled for LBP during the previous day and
various confounders. Results Workers handled on average 1212 [standard deviation
(SD) 861] kg and worked 8.5 (SD 1.8) hours per workday. LBP intensity was higher
in the morning after work- compared with non-workdays [difference of 0.55, 95%
confidence interval (95% CI) 0.39-0.71]. A cumulative effect of consecutive
workdays existed, ie, pain intensity increased approximately 0.30 points per day
for up to three days. For three consecutive work- compared with non-workdays, the
difference was 0.92 (95% CI 0.50-1.34). Higher load resulted in higher pain
intensity in the morning after workdays [0.16 (95% CI 0.02-0.31) per ton lifted],
while no effect was found for number of daily working hours. Conclusion Among
workers with frequent occupational lifting, workdays are associated, in a
cumulative manner, with increased LBP intensity. Furthermore, an exposure
response association exists between workload and increased LBP intensity.
However, the increase in pain intensity was small and future studies should
assess whether long-term consequences exist.
PMID- 27611577
TI - Prediction of Potato Crop Yield Using Precision Agriculture Techniques.
AB - Crop growth and yield monitoring over agricultural fields is an essential
procedure for food security and agricultural economic return prediction. The
advances in remote sensing have enhanced the process of monitoring the
development of agricultural crops and estimating their yields. Therefore, remote
sensing and GIS techniques were employed, in this study, to predict potato tuber
crop yield on three 30 ha center pivot irrigated fields in an agricultural scheme
located in the Eastern Region of Saudi Arabia. Landsat-8 and Sentinel-2 satellite
images were acquired during the potato growth stages and two vegetation indices
(the normalized difference vegetation index (NDVI) and the soil adjusted
vegetation index (SAVI)) were generated from the images. Vegetation index maps
were developed and classified into zones based on vegetation health statements,
where the stratified random sampling points were accordingly initiated. Potato
yield samples were collected 2-3 days prior to the harvest time and were
correlated to the adjacent NDVI and SAVI, where yield prediction algorithms were
developed and used to generate prediction yield maps. Results of the study
revealed that the difference between predicted yield values and actual ones
(prediction error) ranged between 7.9 and 13.5% for Landsat-8 images and between
3.8 and 10.2% for Sentinel-2 images. The relationship between actual and
predicted yield values produced R2 values ranging between 0.39 and 0.65 for
Landsat-8 images and between 0.47 and 0.65 for Sentinel-2 images. Results of this
study revealed a considerable variation in field productivity across the three
fields, where high-yield areas produced an average yield of above 40 t ha-1;
while, the low-yield areas produced, on the average, less than 21 t ha-1.
Identifying such great variation in field productivity will assist farmers and
decision makers in managing their practices.
PMID- 27611579
TI - Standardizing Practice for Intermittent Irrigation of Indwelling Urinary
Catheters.
PMID- 27611580
TI - Impact of Altered Medication Administration Time on Interdisciplinary Bedside
Rounds on Academic Medical Ward.
AB - Interdisciplinary rounds provide a valuable venue for delivering patient-centered
care but are difficult to implement due to time constraints and coordination
challenges. In this article, we describe a unique model for fostering a culture
of bedside interdisciplinary rounds through adjustment of the morning medication
administration time, auditing physician communication with nurses, and displaying
physician performance in public areas. Implementation of this model led to
measurable improvements in physician-to-nurse communication on rounds, teamwork
climate, and provider job satisfaction.
PMID- 27611582
TI - Dietary restraint and weight loss as risk factors for eating pathology.
AB - Measures of dietary restraint do not consistently predict caloric restriction,
and these scales appear inadequate for differentiating between healthy and risky
restraint in individuals. The current study examined the relationship between
self-reported dietary restraint, recent weight loss, body mass index (BMI), and
eating pathology in a college sample to determine if dietary restraint coupled
with caloric restriction would prove to be a more sensitive marker of eating
disorder risk than restraint alone. Participants (N=245) completed a series of
measures evaluating dietary restraint, recent weight loss, and eating habits.
Results suggested that dietary restraint related most consistently to eating
pathology, with more nuanced results for women regarding the relations between
dietary restraint, recent weight loss, and BMI. Findings provided further
evidence that dietary restraint and weight loss may relate to eating pathology
through independent pathways. In addition, recent weight loss may be a relevant
risk factor for women at lower current BMI.
PMID- 27611584
TI - Targeted harassment, subcultural identity and the embrace of difference: a case
study.
AB - This paper examines the significance of experiences and understandings of
targeted harassment to the identities of youth subcultural participants, through
case study research on goths. It does so against a context of considerable recent
public discussion about the victimization of alternative subcultures and a
surprising scarcity of academic research on the subject. The analysis presented
indicates that, although individual direct experiences are diverse, the spectre
of harassment can form an ever-present accompaniment to subcultural life, even
for those who have never been seriously targeted. As such, it forms part of what
it is to be a subcultural participant and comprises significant common ground
with other members. Drawing upon classic and more recent understandings of how
subcultural groups respond to broader forms of outside hostility, we show how the
shared experience of feeling targeted for harassment tied in with a broader
subcultural discourse of being stigmatized by a perceived 'normal' society. The
role of harassment as part of this, we argue, contributed to the strength with
which subcultural identities were felt and to a positive embrace of otherness.
PMID- 27611581
TI - Association between Serum Ferritin Concentrations and Depressive Symptoms among
Chinese Adults: A Population Study from the Tianjin Chronic Low-Grade Systemic
Inflammation and Health (TCLSIHealth) Cohort Study.
AB - Depressive symptoms have become the most important global public health issue.
Iron plays an important role in brain function, cognition, and behavior, and its
impacts on depressive symptoms may be multifactorial with both positive and
negative effects. Previous observational studies focusing on the association
between iron status and depressive symptoms showed inconsistent results. Ferritin
is a ubiquitous intracellular protein that can store and release iron and is
widely used as a clinical biomarker to evaluate iron status. We performed a cross
sectional study to examine the relationship between serum ferritin and depressive
symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade
Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were
assessed using the Chinese version of 20-item self-rating Depression Scale (SDS)
with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40
was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%,
11.0% and 7.0% for SDS >=40, >=45, >=48 and >=50, respectively. With the primary
cut-off point of 40, multiple potential confounding factors were adjusted and the
odds ratios (95% confidence interval) of having elevated depressive symptoms by
quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91,
1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and
fourth quartile, respectively (P for trend = 0.76). Similar relations were
observed with the use of other cut-offs as a definition of depressive symptoms.
In conclusion, there is no significant relationship between serum ferritin
concentrations and depressive symptoms among Chinese adults.
PMID- 27611583
TI - Association of Human Leukocyte Antigen DRB1*15 and DRB1*15:01 Polymorphisms with
Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta
Analysis.
AB - This study aimed to review and quantitatively analyze (1) the association of
aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA
DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA
DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA.
Published studies have reported conflicting and heterogeneous results regarding
the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to
IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge
Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social
Sciences Citation Index databases were searched. All relevant publications were
searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95%
confidence intervals (CI) for the comparison between case-control or cohort
studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and
HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33-3.77), P < 0.01 and 2.50(1.73
3.62), P < 0.01, respectively; and the overall pooled RR was 1.72 (1.30-2.29), P
< 0.01 and 1.59 (1.29-1.96), P < 0.01, respectively. Statistical evidence showed
no publication bias (P > 0.05). Sensitivity analyses revealed that the results
were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA
DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians.
IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients
with AA than in HLA-DRB1*15- and HLA-DRB1*15:01- Asian patients with AA. Future
studies with adequate methodological quality on gene-gene and gene-environment
interactions and gene treatment may yield valid results.
PMID- 27611585
TI - Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software:
Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene
Expression.
AB - The understanding of the genetic basis of the Parkinson's disease (PD) and the
correlation between genotype and phenotype has revolutionized our knowledge about
the pathogenetic mechanisms of neurodegeneration, opening up exciting new
therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in
its early stages and can provide a good start for studies of the molecular
mechanisms that underlie the gene expression variations and the epigenetic
mechanisms that may contribute to the complex and characteristic phenotype of PD.
In this study we used the software TRAM (Transcriptome Mapper) to analyse
publicly available microarray data of a total of 151 PD patients and 130 healthy
controls substantia nigra (SN) samples, to identify chromosomal segments and gene
loci differential expression. In particular, we separately analyzed PD patients
and controls data from post-mortem snap-frozen SN whole tissue and from laser
microdissected midbrain dopamine (DA) neurons, to better characterize the
specific DA neuronal expression profile associated with the late-stage
Parkinson's condition. The default "Map" mode analysis resulted in 10
significantly over/under-expressed segments, mapping on 8 different chromosomes
for SN whole tissue and in 4 segments mapping on 4 different chromosomes for DA
neurons. In conclusion, TRAM software allowed us to confirm the deregulation of
some genomic regions and loci involved in key molecular pathways related to
neurodegeneration, as well as to provide new insights about genes and non-coding
RNA transcripts not yet associated with the disease.
PMID- 27611586
TI - Waking-hour cerebral activations in nightmare disorder: A resting-state
functional magnetic resonance imaging study.
AB - AIM: The purpose of the current study was to explore the cerebral areas involved
in nightmare disorder. METHODS: Fifteen nightmare disorder patients and 15
healthy volunteers were invited to undergo resting-state functional magnetic
resonance imaging and to complete the Nightmare Experience Questionnaire.
RESULTS: The nightmare disorder patients scored higher on the Physical Effect and
Horrible Stimulation scales, had higher values of regional homogeneity in
clusters within the left anterior cingulate cortex and right inferior parietal
lobule, and lower regional homogeneity values within the left superior and
inferior frontal gyri and bilateral middle occipital gyri. Physical Effect was
negatively correlated with regional homogeneity values in anterior cingulate
cortex and inferior parietal lobule in the nightmare disorder group, and was
positively correlated with regional homogeneity value in the inferior frontal
gyrus in the healthy control group. CONCLUSION: To our best knowledge, this is
the first neuroimaging study on nightmare disorder, and we have characterized the
cerebral activities underlying altered hyperarousal and emotion regulation in
nightmare disorder at resting-state.
PMID- 27611588
TI - HLA Class II with Lupus Nephritis in Moroccan Patients.
AB - Lupus nephritis (LN) is a disease with a poor prognosis. The association between
LN and the Human leukocyte antigen (HLA) genes has never been studied on a
Moroccan population. The aim of this work was to evaluate the distribution of the
HLA class II alleles in patients with LN and to determine susceptible and
protective HLA alleles/haplotypes in LN. The association between these alleles,
disease severity of LN, and age at onset were also investigated. Seventy-five
patients with LN were compared with 169 healthy unrelated controls. HLA class II
alleles typing was performed by polymerase chain reaction-sequence-specific
primers (PCR-SSP). A significant increase of HLA-DRB1*15 allele frequency (p =
0.001) and a significant decrease of the HLA-DRB1*04 allele (p = 0.04) were
observed in LN patients. The frequency of HLA-DRB1*15-DQB1*06 haplotype (p =
0.003) was increased in the patients while that of HLA-DRB1*04-DQB1*03 (p =
0.027) was decreased. A significant increase of HLA-DRB1*15 allele frequency (p =
0.0001) and HLA-DRB1*15-DQB1*06 haplotype (p = 0.002) was observed in patients
with class IV LN. In the Moroccan population we demonstrated the positive
association of HLA class II alleles and haplotypes with LN and with a severe form
of nephritis. HLA-DRB1*15 allele does not determine the age of disease onset in
LN.
PMID- 27611589
TI - Abnormal white matter structural connectivity in treatment-naive young adults
with borderline personality disorder.
AB - OBJECTIVE: The pathogenesis of borderline personality disorder (BPD) is not well
understood. We examined the microstructure of white matter in patients with BPD.
METHOD: Treatment-naive young adult with BPD (N = 30) and young-adult healthy
controls (HCs; N = 31) were subjected diffusion tensor imaging (DTI).
Microstructural parameters were analyzed via tract-based spatial statistics
(TBSS) and post hoc tractography. RESULTS: TBSS analysis revealed that, relative
to the HC group, the BPD group had significantly lower fractional anisotropy (FA)
values in the genu and body of the corpus callosum (CC), right superior corona
radiate, right anterior corona radiate, as well as higher radial diffusivity (RD)
in the left anterior thalamic radiation. Tractography showed that FA values of
fiber bundles passing through the fornix were significantly reduced in BPD group
relative to HCs. No significant correlations were observed between clinical
symptom and DTI indices in BPD group (FDR corrected). CONCLUSION: Focal
microstructural alterations were found in BPD group, mainly in the limbic system
and CC. The present findings support the fronto-limbic disconnectivity hypothesis
and suggest that abnormal maturation of white matter structures may play an
important role in mechanism of BPD.
PMID- 27611587
TI - Functional Analysis of Mouse G6pc1 Mutations Using a Novel In Situ Assay for
Glucose-6-Phosphatase Activity and the Effect of Mutations in Conserved Human
G6PC1/G6PC2 Amino Acids on G6PC2 Protein Expression.
AB - Elevated fasting blood glucose (FBG) has been associated with increased risk for
development of type 2 diabetes. Single nucleotide polymorphisms (SNPs) in G6PC2
are the most important common determinants of variations in FBG in humans.
Studies using G6pc2 knockout mice suggest that G6pc2 regulates the glucose
sensitivity of insulin secretion. G6PC2 and the related G6PC1 and G6PC3 genes
encode glucose-6-phosphatase catalytic subunits. This study describes a
functional analysis of 22 non-synonymous G6PC2 SNPs, that alter amino acids that
are conserved in human G6PC1, mouse G6pc1 and mouse G6pc2, with the goal of
identifying variants that potentially affect G6PC2 activity/expression. Published
data suggest strong conservation of catalytically important amino acids between
all four proteins and the related G6PC3 isoform. Because human G6PC2 has very low
glucose-6-phosphatase activity we used an indirect approach, examining the effect
of these SNPs on mouse G6pc1 activity. Using a novel in situ functional assay for
glucose-6-phosphatase activity we demonstrate that the amino acid changes
associated with the human G6PC2 rs144254880 (Arg79Gln), rs149663725 (Gly114Arg)
and rs2232326 (Ser324Pro) SNPs reduce mouse G6pc1 enzyme activity without
affecting protein expression. The Arg79Gln variant alters an amino acid mutation
of which, in G6PC1, has previously been shown to cause glycogen storage disease
type 1a. We also demonstrate that the rs368382511 (Gly8Glu), rs138726309
(His177Tyr), rs2232323 (Tyr207Ser) rs374055555 (Arg293Trp), rs2232326
(Ser324Pro), rs137857125 (Pro313Leu) and rs2232327 (Pro340Leu) SNPs confer
decreased G6PC2 protein expression. In summary, these studies identify multiple
G6PC2 variants that have the potential to be associated with altered FBG in
humans.
PMID- 27611592
TI - An Improved PCR-RFLP Assay for the Detection of a Polymorphism rs2289487 of PLIN1
Gene.
AB - BACKGROUND: In recent research, it has been shown that rs2289487 within the PLIN1
gene has different variants that have been associated with obesity, type 2
diabetes, and other diseases. However, the isochizomers such as the BsmI enzyme
required for detection of this polymorphism through polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP) method are expensive. In this
study, we aimed to explore a novel PCR-RFLP method for identifying the single
nucleotide polymorphism (SNP) of rs2289487 of PLIN1 gene. METHODS: A new
restriction enzyme site was created through created restriction site PCR. In the
forward primer, a deoxynucleotide A was substituted with C, and after PCR a new
restriction enzyme site for BstUI was introduced into the PCR products. A total
of 108 samples from Han Chinese were tested to evaluate this new method. RESULTS:
Allele frequencies in the Asian population were 0.326 for allele A and 0.674 for
allele G, and the genotype frequencies were 12.8% for AA, 39.5% for AG, and 47.7%
for GG. CONCLUSION: The PCR-RFLP with new site for detecting the SNP of rs2289487
is an improved method with low cost and high accuracy.
PMID- 27611593
TI - Flexible Lead-Free BiFeO3/PDMS-Based Nanogenerator as Piezoelectric Energy
Harvester.
AB - Perovskite ferroelectric BiFeO3 has been extensively researched in many
application fields, but has rarely been investigated for the energy conversion of
tiny mechanical motions in electricity in spite of its large theoretical remnant
polarization. Here we demonstrate the fabrication of a flexible piezoelectric
nanogenerator based on BiFeO3 nanoparticles (NPs), which were synthesized using a
sol-gel process. The BiFeO3 NPs-PDMS composite device exhibits an output open
circuit voltage of ~3 V and short circuit current of ~250 nA under repeated hand
pressing. The output generation mechanism from the PNG is discussed on the basis
of the alignment of electric dipoles in the composite film. It is demonstrated
that the output power from the PNG can directly drive the light-emitting diode
(LED) and charge capacitor. These results demonstrate that BiFeO3 nanomaterials
have the potential for large-scale lead-free piezoelectric nanogenerator
applications.
PMID- 27611591
TI - Probing interaction of a fluorescent ligand with HIV TAR RNA.
AB - Trans-activator of Transcription (Tat) antagonists could block the interaction
between Tat protein and its target, trans-activation responsive region (TAR) RNA,
to inhibit Tat function and prevent human immunodeficiency virus type 1 (HIV-1)
replication. For the first time, a small fluorescence ligand, ICR 191, was found
to interact with TAR RNA at the Tat binding site and compete with Tat. It was
also observed that the fluorescence of ICR 191 could be quenched when binding to
TAR RNA and recovered when discharged via competition with Tat peptide or a well
known Tat inhibitor, neomycin B. The binding parameters of ICR 191 to TAR RNA
were determined through theoretical calculations. Mass spectrometry, circular
dichroism and molecular docking were used to further confirm the interaction of
ICR 191 with TAR RNA. Inspired by these discoveries, a primary fluorescence model
for the discovery of Tat antagonists was built using ICR 191 as a fluorescence
indicator and the feasibility of this model was evaluated. This ligand-RNA
interaction could provide a new strategy for research aimed at discovering Tat
antagonists.
PMID- 27611590
TI - Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to
Facilitate Fork Progression and Preserve Genome Integrity.
AB - Replicative DNA helicases expose the two strands of the double helix to the
replication apparatus, but accessory helicases are often needed to help forks
move past naturally occurring hard-to-replicate sites, such as tightly bound
proteins, RNA/DNA hybrids, and DNA secondary structures. Although the
Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork
progression, its genomic targets, dynamics, and mechanisms of action are largely
unknown. Here we address these questions by integrating genome-wide
identification of Pfh1 binding sites, comprehensive analysis of the effects of
Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1
interaction partners by immunoaffinity purification mass spectrometry. Of the 621
high confidence Pfh1-binding sites in wild type cells, about 40% were sites of
fork slowing (as marked by high DNA polymerase occupancy) and/or DNA damage (as
marked by high levels of phosphorylated H2A). The replication and integrity of
tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and
nucleosome depleted regions were particularly Pfh1-dependent. The association of
Pfh1 with genomic integrity at highly transcribed genes was S phase dependent,
and thus unlikely to be an artifact of high transcription rates. Although Pfh1
affected replication and suppressed DNA damage at discrete sites throughout the
genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both
Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the
replication machinery during S phase. Consistent with this interpretation, Pfh1
co-purified with many key replisome components, including the hexameric MCM
helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an
S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA
helicase that interacts with the replisome and promotes replication and
suppresses DNA damage at hard-to-replicate sites. These data provide insight into
mechanisms by which this evolutionarily conserved helicase helps preserve genome
integrity.
PMID- 27611594
TI - Comparison of Dorsal and Volar Percutaneous Approaches in Acute Scaphoid
Fractures: A Meta-Analysis.
AB - The dorsal approach allows better central screw placement along the long axis of
the scaphoid compared with the volar approach in managing acute scaphoid
fractures. However, it is unclear whether the dorsal approach leads to better
clinical outcomes than the volar approach. This meta-analysis compared clinical
outcomes, including the incidence of nonunion, postoperative complications,
overall functional outcome, postoperative pain, grip strength, and range of wrist
motion, between the dorsal and volar percutaneous approaches for the management
of acute scaphoid fractures. Seven studies met the criteria for inclusion in the
meta-analysis. The proportion of patients who developed nonunion (OR 0.74, 95%
CI: 0.21 to 2.54; P = 0.63) and postoperative complications (OR 1.05, 95% CI:
0.45 to 2.44; P = 0.91) did not differ significantly between the dorsal and volar
approaches. Both approaches also led to similar results in terms of overall
functional outcome (95% CI: -0.39 to 0.22; P = 0.57), postoperative pain (95% CI:
-0.52 to 0.46; P = 0.92), grip strength (95% CI: -4.56 to 1.02; P = 0.21),
flexion (95% CI: -2.86 to 1.13; P = 0.40), extension (95% CI: -1.17 to 2.67; P =
0.44), and radial deviation (95% CI: -1.94 to 2.58; P = 0.78). However, ulnar
deviation (95% CI: -7.48 to 0.05; P = 0.05) was significantly greater with the
volar approach. Thus, orthopedic surgeons need to master both the dorsal and
volar percutaneous approaches because not all acute scaphoid fractures can be
dealt with completely with one approach.
PMID- 27611595
TI - Effects of Ionizing Radiation on Physical Properties of Peripherally Inserted
Central Catheter.
AB - Peripherally inserted central catheter (PICC) has been widely used to treat
cancer patients. It is unknown whether or not it can be applied safely during
radiotherapy. The study aimed to investigate the direct effects of gamma
radiation on physical properties of PICC. A total of 60 catheters were included
in this study. Thirty PICCs were exposed to a radiation field, and another 30
PICCs received radiation in a 3-cm homogeneity water equivalent phantom and then
were irradiated. Each group was divided into three subgroups: 10 PICCs were given
conventional fractionation, 2 Gy per fraction, 5 fractions per week; 10 PICCs
were continuously given hypofractionation, 10 Gy per fraction, for 6 weeks; and
10 PICCs were given mock radiation as controls. The physical properties of these
catheters were analyzed after radiation. None of the PICCs leaked under 300-kPa
airflow pressure lasting 15 seconds. Fracture force values and liquid velocity
values of all PICCs were within the normal range. The liquid velocity values of
the control groups were higher than the two groups that received radiation (P <
0.05), and there was no difference between the two irradiation groups (P > 0.05).
There were no statistical differences among the conventional fractionation group,
hypofractionation group, and control group when compared to the fracture force
values in two parts (P > 0.05). The physical property of PICC is quite stable
with a clinically relevant dose of gamma radiation. It is likely that PICC can be
used safely in patients receiving radiotherapy, although further in vivo and
clinical studies are required.
PMID- 27611596
TI - Visualization of haemophilic arthropathy in F8-/- rats by ultrasonography and
micro-computed tomography.
AB - INTRODUCTION: A major complication of haemophilia is haemophilic arthropathy
(HA), a debilitating disorder with an incompletely defined pathobiology. High
resolution imaging may provide new knowledge about onset and progression of HA,
and thereby support identification of new treatment opportunities. Recently, a F8
/- rat model of HA was developed. The size of the rat allows for convenient and
high resolution imaging of the joints, which could enable in vivo studies of HA
development. AIM: To determine whether HA in the F8-/- rat can be visualized
using ultrasonography (US) and micro-computed tomography (MUCT). METHODS: Sixty
F8-/- and 20 wild-type rats were subjected to a single or two induced knee
bleeds. F8-/- rats were treated with either recombinant human FVIII (rhFVIII) or
vehicle before the induction of knee bleeds. Haemophilic arthropathy was
visualized using in vivo US and ex vivo MUCT, and the observations correlated
with histological evaluation. RESULTS: US and MUCT detected pathologies in the
knee related to HA. There was a strong correlation between disease severity
determined by MUCT and histopathology. rhFVIII treatment reduced the pathology
identified with both imaging techniques. CONCLUSION: US and MUCT are suitable
imaging techniques for detection of blood-induced joint disease in F8-/- rats and
may be used for longitudinal studies of disease progression.
PMID- 27611597
TI - Maternal Dietary Patterns and Practices and Birth Weight in Northern Ghana.
AB - BACKGROUND: Adequate maternal nutrition is a key factor for achieving good
pregnancy outcomes. Moreover, inadequate dietary intake during pregnancy is
considered an important contributor to maternal malnutrition in developing
countries. Although some studies have examined the effect of the entire diet on
birth outcome, most studies have been very narrow because they considered the
effect of single nutrient. The single nutrient approach is a major setback
because usually several nutrient deficiencies are more likely to occur than
single deficiencies especially in low-income settings. OBJECTIVES: The main aim
of this study was to investigate the association between maternal dietary
patterns, and practices and birth weight in Northern Ghana. PARTICIPANT SETTINGS:
A facility-based cross-sectional survey was performed in two districts in the
Northern Region of Ghana. The selected districts were the Tamale Metropolis and
Savelugu-Nanton District. These districts were purposively sampled to represent a
mix of urban, peri-urban and rural populations, therefore ensuring that the
distribution in social groups of the study population was similar to the entire
population of the region. In all, 578 mothers who were drawing antenatal and
postnatal care services were interviewed using a questionnaire, which asked the
mothers about their frequency of consumption of individual foods per week since
they became pregnant or when they were pregnant. STATISTICAL ANALYSIS: We
determined dietary patterns by applying a factor analysis with a varimax rotation
using STATA. Multivariate analysis was used to establish association between
maternal factors and dietary patterns. Logistic regression was used to assess the
association between dietary practices and patterns and birth weight. RESULTS:
Women who ate outside the home twice a week (OR = 1.6 & 95% CI; 1.1-2.45, P;
0.017) and those who practiced 'pica' (OR = 1.7 & 95% CI; 1.16-2.75, P; 0.008)
had increased odds for low birth. Two dietary patterns were identified-namely
'health conscious' and 'non-health conscious'. Health conscious diet (OR = 0.23
95% CI 0.12-0.45 per standard deviation change in scores, P; <0.0001) and dietary
diversity score (OR = 0.10 95% CI 0.04-0.13 per standard deviation change in
scores, P; <0.0001) showed a protective effect for low birth weight respectively
after adjusting for gestational age. CONCLUSION: Mothers who practiced good
nutrition such as consuming foods across and within the various food groups were
less likely to have low birth weight babies. Our findings buttress the importance
of optimal nutrition during pregnancy.
PMID- 27611598
TI - Correlation of Axial Spondyloarthritis with Anxiety and Depression.
AB - BACKGROUND This study compared anxiety and depression in patients with
nonradiographic axial spondyloarthritis (nr-axSpA) versus patients with
ankylosing spondylitis (AS), and examined the relationship between clinical
characteristics and psychological status. MATERIAL AND METHODS Patients diagnosed
with axial spondyloarthritis (axSpA) were recruited for the study. Disease status
was evaluated by the bath ankylosing spondylitis disease activity index (BASDAI),
the bath ankylosing spondylitis functional index, visual analog scale, and the
level of inflammatory markers. Psychological status was evaluated by the self
rating anxiety scale (SAS) and the self-rating depression scale (SDS). RESULTS
Sixty patients with axSpA were enrolled in the study, including 40 patients with
AS and 20 patients with nr-axSpA. Patients with AS and patients with nr-axSpA had
similar disease status and psychological status. Anxiety was significantly
associated with disease status and SDS score (P<0.05 for all), whereas BASDAI
(odds ratio [OR]=0.28, 95% CI=0.08-0.97, P=0.045) and SDS (OR=0.90, 95% CI=0.82
0.98, P=0.014) protected against anxiety. Depression was obviously correlated
with smoking history, disease status, and SAS score (P<0.05 for all). Smoking
history (OR=10.18, 95% CI=1.23-84.23, P=0.031) and SAS score (OR=0.85, 95%
CI=0.75-0.97, P=0.014) were negatively correlated with risk of depression.
CONCLUSIONS Patients with AS and patients with nr-axSpA had similar psychological
status in terms of anxiety and depression. Disease status and smoking were
significantly correlated with psychological status. Patients with higher SAS
scores were more likely to have depression. The results of this study may be
helpful to clinically guide psychological interventions for patients with axSpA.
PMID- 27611600
TI - A serologic weakly reactive RhD is caused by a c.496C>G (p.His166Asp) in RHD
gene.
PMID- 27611599
TI - The effect of bilirubin on the excitability of mitral cells in the olfactory bulb
of the rat.
AB - Olfactory dysfunction is a common clinical phenomenon observed in various liver
diseases. Previous studies have shown a correlation between smell disorders and
bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known
neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the
first relay in the olfactory system, has not been examined. We investigated the
effect of bilirubin (>3 MUM) on mitral cells (MCs), the principal output neurons
of the MOB. Bilirubin increased the frequency of spontaneous firing and the
frequency but not the amplitude of spontaneous excitatory postsynaptic currents
(sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested.
Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and alpha
amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists.
Furthermore, we found that bilirubin increased the frequency of intrinsic firing
independent of synaptic transmission in MCs. Our findings suggest that bilirubin
enhances glutamatergic transmission and strengthens intrinsic firing independent
of synaptic transmission, all of which cause hyperexcitability in MCs. Our
findings provide the basis for further investigation into the mechanisms
underlying olfactory dysfunction that are often observed in patients with severe
liver disease.
PMID- 27611601
TI - Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1.
AB - An integrated methodology is described to establish ligand requirements for
heparan sulfate (HS) binding proteins based on a workflow in which HS
octasaccharides are produced by partial enzymatic degradation of natural HS
followed by size exclusion purification, affinity enrichment using an immobilized
HS-binding protein of interest, putative structure determination of isolated
compounds by a hydrophilic interaction chromatography-high-resolution mass
spectrometry platform, and chemical synthesis of well-defined HS oligosaccharides
for structure-activity relationship studies. The methodology was used to
establish the ligand requirements of human Roundabout receptor 1 (Robo1), which
is involved in a number of developmental processes. Mass spectrometric analysis
of the starting octasaccharide mixture and the Robo1-bound fraction indicated
that Robo1 has a preference for a specific set of structures. Further analysis
was performed by sequential permethylation, desulfation, and
pertrideuteroacetylation followed by online separation and structural analysis by
MS/MS. Sequences of tetrasaccharides could be deduced from the data, and by
combining the compositional and sequence data, a putative octasaccharide ligand
could be proposed (GlA-GlcNS6S-IdoA-GlcNS-IdoA2S-GlcNS6S-IdoA-GlcNAc6S). A
modular synthetic approach was employed to prepare the target compound, and
binding studies by surface plasmon resonance (SPR) confirmed it to be a high
affinity ligand for Robo1. Further studies with a number of tetrasaccharides
confirmed that sulfate esters at C-6 are critical for binding, whereas such
functionalities at C-2 substantially reduce binding. High affinity ligands were
able to reverse a reduction in endothelial cell migration induced by Slit2-Robo1
signaling.
PMID- 27611602
TI - Optical sensors to gain mechanistic insights into signaling assemblies.
AB - Protein complexes play a major role in transducing information from outside the
cell into instructions for growth and survival, and understanding how these
complexes relay and shape intracellular signals has been a central question in
signaling biology. Fluorescent proteins have proven paramount in opening windows
for researchers to peer into the architecture and inner workings of signaling
assemblies within the living cell and in real-time. In this review, we will
provide readers with a current perspective on the development and use of
genetically encoded optical probes to dissect the function of signaling
complexes.
PMID- 27611603
TI - Effect of fructose on promoting fengycin biosynthesis in Bacillus
amyloliquefaciens fmb-60.
AB - AIMS: To explore the influence of carbohydrates on the production of fengycin by
Bacillus amyloliquefaciens fmb-60. METHODS AND RESULTS: Fermentation and gene
expression levels were examined following culture supplementation with fructose,
arabinose and sorbitol. Compared with other carbohydrates, fructose most
efficiently increased the concentration of the essential component amino acids
for fengycin synthesis in the cell. The maximum production of fengycin was found
to be 392.87 mg l-1 , increased by 76% in fed-batch fermentation. Furthermore,
fructose enhanced the biosynthesis of fengycin by increasing the expression of
fengycin synthetase genes (fenA, fenB, fenC, fenD, fenE and fenTE) and regulatory
genes (comA, degU, degQ and sigma H). CONCLUSION: Fructose is important for
fengycin production in B. amyloliquefaciens fmb-60, and it could enhance fengycin
biosynthesis by raising the expression of the fengycin synthetase genes and
upregulating signal factors. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
identify regulatory mechanisms involved in fengycin biosynthesis and provide an
effective method to enhance production of fengycin.
PMID- 27611604
TI - Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.
AB - OBJECTIVE: Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3)
was reported to be related to obesity, Metabolic syndrome (MS), and type 2
diabetes mellitus in various adult studies, there is a lack of data in children.
In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish
children and adolescent with and without MS and compared the results with that of
controls. METHODS: One hundred and forty eight obese and 63 age- and sex-matched
control subjects were enrolled in the study. Obesity classification was carried
out according to body mass index. World Health Organization and National
Cholesterol Education Program criteria were used for the diagnosis of MS.
Genotyping procedure was carried out by polymerase chain reaction and Sanger
sequencing protocol. RESULTS: The frequency of rs2280148 polymorphism was
significantly higher in obese subjects with MS than in the control group, whereas
the frequency of rs8064821 polymorphism was significantly higher in obese
subjects with MS than in obese children without MS. CONCLUSION: The significant
associations of certain SOCS3 polymorphisms with obesity parameters in both MS
and MS -related insulin resistance, hypertension, and fatty liver suggest that
polymorphisms in this gene may play a role in the pathogenesis of MS and also
that they can be potentially used as a marker for attenuated or aggressive
disease.
PMID- 27611605
TI - Dental implants in diabetic patients: retrospective cohort study reporting on
implant survival and risk indicators for excessive marginal bone loss at 5 years.
AB - More studies evaluating the outcome of dental implant restorations in diabetics
are needed. To investigate the outcome of immediate function implant
rehabilitations in diabetic patients. This retrospective cohort study included 70
diabetic patients (type 1 = six patients; type 2 = 64 patients; 33 females and 37
males, mean age=59 years), rehabilitated with 352 implants. Primary outcome
measure was implant survival estimated at 5 years through the Kaplan-Meier
product limit estimator using the patient as unit of analysis (first implant
failure as reference); secondary outcome measures were marginal bone loss and
biological complications. Risk indicators associated with bone loss >2.0 mm were
tested in a multivariate logistic regression model. The level of significance
considered was 5%. Seven patients were lost to follow-up (10%). Seven patients
lost ten implants rendering a global implant cumulative survival rate for
diabetic patients of 89.8% (type 1 = 80.0%; type 2 = 90.5%). The average (95%
confidence interval) marginal bone loss at 1 and 5 years was 1.64 mm (0.00;3.32)
and 2.55 mm (1.38;3.72) for type 1 diabetic patients, 0.79 mm (0.59;1.00) and
1.45 mm (1.09;1.82) for type 2 diabetic patients and 0.88 mm (0.65;1.10) and 1.56
mm (1.21;1.91) overall. Biological complications occurred in seven patients.
Female gender (OR = 28.1) and smoking habits (OR = 10.3) were risk indicators for
marginal bone loss >2.0 mm at 5 years when controlled for other variables of
interest. Implant rehabilitations represent a valid treatment for diabetic
patients, with a good risk/benefit ratio. Female gender and smoking habits were
risk indicators for a higher marginal bone resorption at 5 years.
PMID- 27611606
TI - Development and validation of a quantitative snack and beverage food frequency
questionnaire for adolescents.
AB - BACKGROUND: A short, reliable and valid tool to measure snack and beverage
consumption in adolescents, taking into account the correct definitions, would
benefit both epidemiological and intervention research. The present study aimed
to develop a short quantitative beverage and snack food frequency questionnaire
(FFQ) and to assess the reliability and validity of this FFQ against three 24-h
recalls. METHODS: Reliability was assessed by comparing estimates of the FFQ
administered 14 days apart (FFQ1 and FFQ2) in a convenience sample of 179
adolescents [60.3% male; mean (SD) 14.7 (0.9) years]. Validity was assessed by
comparing FFQ1 with three telephone-administered 24-h recalls in a convenience
sample of 99 adolescents [52.5% male, mean (SD) 14.8 (0.9) years]. Reliability
and validity were assessed using Bland-Altman plots, classification agreements
and correlation coefficients for the amount and frequency of consumption of
unhealthy snacks, healthy snacks, unhealthy beverages, healthy beverages, and for
the healthy snack and beverage ratios. RESULTS: Small mean differences (FFQ1
versus FFQ2) were observed for reliability, ranking ability ranged from fair to
substantial, and Spearman coefficients fell within normal ranges. For the
validity, mean differences (FFQ1 versus recalls) were small for beverage intake
but large for snack intake, except for the healthy snack ratio. Ranking ability
ranged from slightly to moderate, and Spearman coefficients fell within normal
ranges. CONCLUSIONS: Reliability and validity of the FFQ for all outcomes were
found to be acceptable at a group level for epidemiological purposes, whereas for
intervention purposes only the healthy snack and beverage ratios were found to be
acceptable at a group level.
PMID- 27611607
TI - Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone
Secretion.
AB - OBJECTIVE: We asked if leptin and its cognate receptor were present in normal and
diseased parathyroid glands, and if so, whether they had any functional effects
on parathyroid hormone (PTH) secretion in parathyroid neoplasms. BACKGROUND: The
parathyroid glands acting through PTH play a critical role in the regulation of
serum calcium. Based on leptin's recently discovered role in bone metabolism, we
hypothesized these glands were the sites of a functional interaction between
these 2 hormones. METHODS: From July 2010 to July 2011, 96 patients were enrolled
in a prospective study of leptin and hyperparathyroidism, all of whom were
enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for
surgical intervention provided informed consent. Immediately after
parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased
parathyroid tissue was prepared and processed according to requirements of the
following: in situ hybridization, immunohistochemistry, immunofluorescence by
conventional and spinning disc confocal microscopy, electron microscopy,
parathyroid culture, whole organ explant, and animal model assays. RESULTS:
Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were
detected in an overlapping fashion in parathyroid chief cells in adenoma and
hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT
PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous
leptin uptake in cultured parathyroid cells. PTH secretion in explants increased
in response to leptin and decreased with leptin receptor signaling inhibition by
AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited
increased PTH levels from baseline. CONCLUSIONS: Taken together, these data
suggest that leptin is a functionally active product of the parathyroid glands
and stimulates PTH release.
PMID- 27611608
TI - Ampulla of Vater Carcinoma: Sequencing Analysis Identifies TP53 Status as a Novel
Independent Prognostic Factor and Potentially Actionable ERBB, PI3K, and WNT
Pathways Gene Mutations.
AB - OBJECTIVE: To identify molecular prognostic factors and potentially actionable
mutations in ampulla of Vater cancer (AVC). BACKGROUND: The largely variable
outcomes of AVCs make clinical decisions difficult regarding the need of
postsurgical therapy, which is based on morphological and immunohistochemical
classification that do not adequately consider the varying degrees of
heterogeneity present in many AVCs. No approved targeted therapies for AVC exist,
but some show promising results requiring better molecular characterization to
identify potential responders. METHODS: We assessed 80 AVCs for the prognostic
value of mutations of kirsten rat sarcoma (KRAS), neuroblastoma RAS (NRAS), B
rapidly accelerated fibrosarcoma (BRAF), TP53, and 4 membrane erythroblastosis
oncogene B (ERBB) receptor tyrosine kinases (EGFR-ERBB1, HER2-ERBB2, HER3-ERBB3,
HER4-ERBB4) amenable to pharmacological inhibition. Moreover, we evaluated
mutations in 16 key components of rat sarcoma (RAS), phosphatidylinositol-4,5
bisphosphate 3-kinase (PI3K), protein 53 (P53), transforming growth factor beta
(TGF-beta), and wingless/integrated (WNT) pathways, recently associated to AVC by
whole-exome sequencing. RESULTS: TP53 and KRAS were mutated in 41% and 35% of
cases, respectively, and emerged as independent prognostic factors together with
tumor stage and regardless of the histotype (TP53: P = 0.0006; KRAS: P = 0.0018;
stage IIB: P = 0.0117; stage III-IV: P = 0.0020). ERBB, WNT and PI3K pathway
genes were mutated in 37.5% of cases. CONCLUSIONS: KRAS and TP53 mutations are
negative predictors of survival in AVCs, regardless of histotype. Potentially
actionable mutations in ERBB, WNT, and PI3K signaling pathway genes are present
in 37.5% of all cases. These might be amenable to target therapy using available
drugs like Everolimus in PI3K-mutated cases or compounds under active screening
against ERBB and WNT signaling.
PMID- 27611609
TI - Development and Validation of Quality Criteria for Providing Patient- and Family
centered Injury Care.
AB - OBJECTIVE: The aim of this study was to develop and evaluate the content validity
of quality criteria for providing patient- and family-centered injury care.
BACKGROUND: Quality criteria have been developed for clinical injury care, but
not patient- and family-centered injury care. METHODS: Using a modified Research
AND Development Corporation (RAND)/University of California, Los Angeles (UCLA)
Appropriateness Methodology, a panel of 16 patients, family members, injury and
quality of care experts serially rated and revised criteria for patient- and
family-centered injury care identified from patient and family focus groups. The
criteria were then sent to 384 verified trauma centers in the United States,
Canada, Australia, and New Zealand for evaluation. RESULTS: A total of 46
criteria were rated and revised by the panel over 4 rounds of review producing 14
criteria related to clinical care (n = 4; transitions of care, pain management,
patient safety, provider competence), communication (n = 3; information for
patients/families; communication of discharge plans to patients/families,
communication between hospital and community providers), holistic care (n = 4;
patient hygiene, kindness and respect, family access to patient, social and
spiritual support) and end-of-life care (n = 3; decision making, end-of-life
care, family follow-up). Medical directors, managers, or coordinators
representing 254 trauma centers (66% response rate) rated 12 criteria to be
important (95% of responses) for patient- and family-centered injury care. Fewer
centers rated family access to the patient (80%) and family follow-up after
patient death (65%) to be important criteria. CONCLUSIONS: Fourteen-candidate
quality criteria for patient- and family-centered injury care were developed and
shown to have content validity. These may be used to guide quality improvement
practices.
PMID- 27611610
TI - Multicenter Stratified Comparison of Hospital Costs Between Laparoscopic and Open
Colorectal Cancer Resections: Influence of Tumor Location and Operative Risk.
AB - OBJECTIVE: To compare actual 90-day hospital costs between elective open and
laparoscopic colon and rectal cancer resection in a daily practice multicenter
setting stratified for operative risk. BACKGROUND: Laparoscopic resection has
developed as a commonly accepted surgical procedure for colorectal cancer. There
are conflicting data on the influence of laparoscopy on hospital costs, without
separate analyses based on operative risk. METHODS: Retrospective analyses using
a population-based database (Dutch Surgical Colorectal Audit). All elective
resections for a T1-3N0-2M0 stage colorectal cancer were included between 2010
and 2012 in 29 Dutch hospitals. Operative risk was stratified for age (<75 years
or >=75 years) and ASA status (I-II/III-IV). Ninety-day hospital costs were
measured uniformly in all hospitals based on time-driven activity-based costing.
RESULTS: Total 90-day hospital costs ranged from &OV0556;10474 to &OV0556;20865
in the predefined subgroups. For colon cancer surgery (N = 4202), laparoscopic
resection was significant less expensive than open resection in all subgroups,
savings because of laparoscopy ranged from &OV0556;409 (<75 years ASA I-II) to
&OV0556;1932 (>=75 years ASA I-II). In patients >=75 years and ASA I-II,
laparoscopic resection was associated with 46% less mortality (P = 0.05), 41%
less severe complications (P < 0.001), 25% less hospital stay (P = 0.013), and
65% less ICU stay (P < 0.001). For rectal cancer surgery (N=2328), all
laparoscopic subgroups had significantly higher total hospital costs, ranging
from &OV0556;501 (<75 years ASA I-II) to &OV0556;2515 (>=75 years ASA III-IV).
CONCLUSIONS: Laparoscopic resection resulted in the largest cost reduction in
patients over 75 years with ASA I-II undergoing colonic resection, and the
largest cost increase in patients over 75 years with ASA III-IV undergoing rectal
resection as compared with an open approach.
PMID- 27611611
TI - Liver Transplantation for Alcoholic Hepatitis.
PMID- 27611612
TI - Global Gene Expression Change Induced by Major Thoracoabdominal Surgery.
AB - OBJECTIVE: To test the hypothesis that major thoracoabdominal surgery induces
gene expression changes associated with adverse outcomes. BACKGROUND: Widely
different traumatic injuries evoke surprisingly similar gene expression profiles,
but there is limited information on whether the iatrogenic injury caused by major
surgery is associated with similar patterns. METHODS: With informed consent,
blood samples were obtained from 50 patients before and after open transhiatal
esophagectomy or pancreaticoduodenectomy. Twelve cases with complicated
recoveries (death, infection, venous thromboembolism) were matched with 12 cases
with uneventful recoveries. Global gene expression was assayed using human
microarray chips. A 2-fold change with a corrected P < 0.05 was considered
differentially expressed. RESULTS: In these 24 patients, 522 genes were
differentially expressed after surgery; 248 (48%) were upregulated (innate
immunity and inflammation) and 274 (52%) were downregulated [adaptive immunity
(antigen presentation, T-cell function)]. Hierarchical clustering of the profile
reliably predicted pre- and postoperative status. The within-patient change was
3.08 +/- 0.91-fold. There was no measurable association with age, malignancy,
procedure, surgery length, operative blood loss, or transfusion requirements, but
was positively associated with postoperative infection (3.81 +/- 0.97 vs 2.79 +/-
0.73; P = 0.009) and hospital length of stay (r = 0.583, P = 0.003). Venous
thromboembolism and mortality each occurred in one patient, thus no associations
were possible. CONCLUSIONS: Major surgery induces a quantifiable pattern of gene
expression change that is associated with adverse outcome. This could reflect
early impaired adaptive immunity and suggests potential therapeutic targets to
improve postoperative recovery.
PMID- 27611613
TI - Stopping the Bleeding Is Not Enough.
PMID- 27611614
TI - Modified ALPPS Procedures Avoiding Division of Portal Pedicles.
AB - OBJECTIVE: We describe a modified procedure associating liver partition and
portal vein ligation for staged hepatectomy (ALPPS) including portal pedicle
preservation during parenchymal division, thus avoiding necrosis. BACKGROUND:
Although ALPPS recently has been advocated for treating advanced liver tumors,
sepsis originating from the ischemic area produced by parenchymal division
increases mortality, accounting for one-third of postoperative deaths. METHODS:
Our procedure differs from the original ALPPS technique by sparing portal
pedicles at the transection plane, thus maintaining blood supply. The preserved
pedicles are segment 4 (S4) in right lobectomy plus right portal vein ligation
(PVL), S1 in extended right hepatectomy (extended to S1) plus right PVL, lateral
portal pedicles of the right paramedian sector (RPS) in extended right lateral
sectoriectomy plus lateral PVL, and both portal pedicles of the lateral RPS and
S1 in extended right lateral sectoriectomy with S1 resection plus lateral PVL.
RESULTS: These procedures were performed in 5 patients. Morbidity rates at first-
and second-stage operations were 0% and 80%, without mortality. Mean hypertrophy
of the future liver remnant was 1.638 +/- 0.384 a week after the first-stage
procedure. CONCLUSIONS: Our technique stimulates rapid hypertrophy and may
improve safety in ALPPS.
PMID- 27611615
TI - Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL
to the Story.
AB - OBJECTIVE: We sought to develop a "Model Of Recurrence After Liver transplant"
(MORAL) for hepatocellular carcinoma (HCC). BACKGROUND: The Milan criteria are
used to allocate livers to patients with HCC requiring liver transplantation (LT)
but do not include objective measures of tumor biology. Biological markers
including the neutrophil-lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) have
been associated with recurrence risk. METHODS: Prospective cohort study of adults
undergoing LT for HCC between January 2001 and December 2012. RESULTS: A total of
339 patients were included. On multivariable Cox regression analysis, 3
preoperatively available factors were independent predictors of worse recurrence
free survival (RFS), namely, an NLR >= 5 (P < 0.0001, hazard ratio, HR: 6.2), AFP
> 200 (P < 0.0001, HR: 3.8), and Size >3 cm (P < 0.001, HR: 3.2). The Pre-MORAL
score was constructed from the hazard ratios and assigning patients points in an
additive fashion, with a minimum of 0 points (no factors) and a maximum of 13
points (all 3 factors). The highest risk patients in the Pre-MORAL had a 5-year
RFS of 17.9% compared with 98.6% for the low risk group (P < 0.0001). The post
MORAL was constructed similarly using the 4 postoperatively available independent
predictors of worse RFS, grade 4 HCC's (P < 0.0001, HR: 5.6), vascular invasion
(P = 0.019, HR: 2.0), size >3 cm (P < 0.0001, HR: 3.2) and number >3 (P = 0.048,
HR: 1.8). The pre- and post-MORAL were superior to Milan at predicting recurrence
with c-statistics of 0.82 and 0.87, compared with 0.63, respectively. We then
combined the scores to produce a combo-MORAL, with a c-statistic of 0.91 for
predicting recurrence. CONCLUSIONS: The MORAL score provides a simple, highly
accurate tool for predicting recurrence and risk-stratification pre- and
postoperatively.
PMID- 27611616
TI - Invited Commentary: Pasireotide and the Prevention of Pancreatic Fistula After
Pancreatectomy: "The Continued Search for Harry Potter's Liquid Luck".
PMID- 27611617
TI - Rising Bilateral Mastectomy Rates Among Neoadjuvant Chemotherapy Recipients in
California From 1998 to 2012.
AB - OBJECTIVE: To study the impact of rising bilateral mastectomy rates among
neoadjuvant chemotherapy (NAC) recipients in California. BACKGROUND: NAC for
operable breast cancer (BC) can downstage disease and facilitate breast
conservation. We assessed trends in NAC use and surgical procedures in California
from January 1, 1998 to December 31, 2012 using statewide population-based cancer
registry data. METHODS: A total of 236,797 females diagnosed with stage I-III BC
were studied. Information regarding NAC, adjuvant chemotherapy (aCT), breast
conserving surgery (BCS), bilateral mastectomy (BLM), and unilateral mastectomy
(ULM) was abstracted from the medical records. Multivariable polytomous logistic
regression was used to estimate odds ratios (OR) of receiving NAC and of type of
surgery after NAC. RESULTS: Approximately, 40.1% (94,980) of patients received
chemotherapy: 87% (82,588) aCT and 13.0% (12,392) NAC. NAC use more than doubled
over time and increased with stage (Stage I, 0.7%; Stage III, 29.9%).
Multivariable predictors of NAC treatment were stage (III), younger age (<40
yrs), Black or Hispanic race/ethnicity versus non-Hispanic White (OR 1.10, 95%
confidence interval (CI) 1.05-1.16), and care at a National Cancer Institute
(NCI)-designated center (OR 1.70, CI 1.58-1.82). Most NAC recipients (68.4%) had
mastectomies, and 14.3% of them underwent BLM. In contrast, 47.9% aCT patients
had mastectomies with 7.3% BLM. The only independent predictor of BCS after NAC
was care at a NCI-designated center (OR 1.28, CI 1.10-1.49), and of BLM, age <40
years versus 50 to 64 years (OR 2.59, CI 2.21-3.03), or residence in the highest
socioeconomic neighborhood quintile versus lowest (OR 2.10, CI 1.67-2.64).
CONCLUSIONS: NAC use remains low. Predictors of surgery type after NAC were
sociodemographic rather than clinical, raising concern for disparities in care
access.
PMID- 27611618
TI - What Are the Principles That Guide Behaviors in the Operating Room?: Creating a
Framework to Define and Measure Performance.
AB - OBJECTIVE: To identify the core principles that guide expert intraoperative
behaviors and to use these principles to develop a universal framework that
defines intraoperative performance. BACKGROUND: Surgical outcomes are associated
with intraoperative cognitive skills. Yet, our understanding of factors that
control intraoperative judgment and decision-making are limited. As a result,
current methods for training and measuring performance are somewhat subjective
more task rather than procedure-oriented-and usually not standardized. They thus
provide minimal insight into complex cognitive processes that are fundamental to
patient safety. METHODS: Cognitive task analyses for 6 diverse surgical
procedures were performed using semistructured interviews and field observations
to describe the thoughts, behaviors, and actions that characterize and guide
expert performance. Verbal data were transcribed, supplemented with content from
published literature, coded, thematically analyzed using grounded-theory by 4
independent reviewers, and synthesized into a list of items. RESULTS: A
conceptual framework was developed based on 42 semistructured interviews lasting
45 to 120 minutes, 5 expert panels and 51 field observations involving 35
experts, and 135 sources from the literature. Five domains of intraoperative
performance were identified: psychomotor skills, declarative knowledge, advanced
cognitive skills, interpersonal skills, and personal resourcefulness. Within the
advanced cognitive skills domain, 21 themes were perceived to guide the behaviors
of surgeons: 18 for surgical planning and error prevention, and 3 for
error/injury recognition, rescue, and recovery. The application of these thought
patterns was highly case-specific and variable amongst subspecialties,
environments, and individuals. CONCLUSIONS: This study provides a comprehensive
definition of intraoperative expertise, with greater insight into the complex
cognitive processes that seem to underlie optimal performance. This framework
provides trainees and other nonexperts with the necessary information to use in
deliberate practice and the creation of effective thought habits that
characterize expert performance. It may help to identify gaps in performance, and
to isolate root causes of surgical errors with the ultimate goal of improving
patient safety.
PMID- 27611619
TI - Burden of Surgical Conditions in Uganda: A Cross-sectional Nationwide Household
Survey.
AB - OBJECTIVE: To quantify the burden of surgical conditions in Uganda. BACKGROUND:
Data on the burden of disease have long served as a cornerstone to health
policymaking, planning, and resource allocation. Population-based data are the
gold standard, but no data on surgical burden at a national scale exist;
therefore, we adapted the Surgeons OverSeas Assessment of Surgical Need survey
and conducted a nation-wide, cross-sectional survey of Uganda to quantify the
burden of surgically treatable conditions. METHODS: The 2-stage cluster sample
included 105 enumeration areas, representing 74 districts and Kampala Capital
City Authority. Enumeration occurred from August 20 to September 12, 2014. In
each enumeration area, 24 households were randomly selected; the head of the
household provided details regarding any household deaths within the previous 12
months. Two household members were randomly selected for a head-to-toe verbal
interview to determine existing untreated and treated surgical conditions.
RESULTS: In 2315 households, we surveyed 4248 individuals: 461 (10.6%) reported 1
or more conditions requiring at least surgical consultation [95% confidence
interval (CI) 8.9%-12.4%]. The most frequent barrier to surgical care was the
lack of financial resources for the direct cost of care. Of the 153 household
deaths recalled, 53 deaths (34.2%; 95% CI 22.1%-46.3%) were associated with
surgically treatable signs/symptoms. Shortage of time was the most frequently
cited reason (25.8%) among the 11.6% household deaths that should have, but did
not, receive surgical care (95% CI 6.4%-16.8%). CONCLUSIONS: Unmet surgical need
is prevalent in Uganda. There is an urgent need to expand the surgical care
delivery system starting with the district-level hospitals. Routine surgical data
collection at both the health facility and household level should be implemented.
PMID- 27611621
TI - No Cytokine Is an Island: IL-6 Alone Is Not Sufficient to Predict Morbidity After
a Major Abdominal Surgery.
PMID- 27611620
TI - Acute Kidney Injury in Burn Patients: Clinically Significant Over the Initial
Hospitalization and 1 Year After Injury: An Original Retrospective Cohort Study.
AB - OBJECTIVE: To examine the development of acute kidney injury (AKI) after burn
injury as an independent risk factor for increased morbidity and mortality over
initial hospitalization and 1-year follow-up. BACKGROUND: Variability in fluid
resuscitation and difficulty recognizing early sepsis are major barriers to
preventing AKI after burn injury. Expanding our understanding of the burden AKI
has on the clinical course of burn patients would highlight the need for
standardized protocols. METHODS: We queried the Healthcare Cost and Utilization
Project State Inpatient Databases in the states of Florida and New York during
the years 2009 to 2013 for patients over age 18 hospitalized with a primary
diagnosis of burn injury using ICD-9 codes. We identified and grouped 18,155
patients, including 1476 with burns >20% total body surface area, by presence of
AKI. Outcomes were compared in these cohorts via univariate analysis and
multivariate logistic regression models. RESULTS: During initial hospitalization,
AKI was associated with increased pulmonary failure, mechanical ventilation,
pneumonia, myocardial infarction, length of stay, cost, and mortality, and also a
lower likelihood of being discharged home. One year after injury, AKI was
associated with development of chronic kidney disease, conversion to chronic
dialysis, hospital readmission, and long-term mortality. CONCLUSIONS: AKI is
associated with a profound and severe increase in morbidity and mortality in burn
patients during initial hospitalization and up to 1 year after injury. Consensus
protocols for initial burn resuscitation and early sepsis recognition and
treatment are crucial to avoid the consequences of AKI after burn injury.
PMID- 27611622
TI - Diagnostic accuracy of computed tomography urography and visual assessment during
ureterorenoscopy in upper tract urothelial carcinoma.
AB - OBJECTIVE: To investigate diagnostic accuracy of multiphase computed tomography
urography (MCTU) and visual assessment at ureterorenoscopy (URS) for detection of
upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Consecutive
patients referred to our tertiary care centre were included in a prospective
study covering the period 2005 to 2012. The patients underwent initial imaging
and URS with focal samples taken. Cytopathological results served as reference
standard. RESULTS: We investigated 174 renal units (RUs; renal pelvis and
adjacent ureter) in 148 patients. UTUC was found in 104 RUs. MCTU had an accuracy
of 0.74, sensitivity of 0.89, specificity of 0.51, positive predictive value of
0.73, and negative predictive value of 0.75; corresponding values for URS were
0.84, 0.84, 0.85, 0.89, and 0.78, respectively. MCTU had significantly higher
sensitivity and accuracy compared with other imaging techniques (P<0.05).
Compared with MCTU, URS had similar sensitivity but significantly greater
specificity and accuracy. CONCLUSION: Both MCTU and URS are important tools in
the diagnostic evaluation of UTUC although neither of those techniques achieves
100% accuracy. MCTU should be chosen as the radiographical method if there are no
contraindications and URS should always be combined with focal cytology and
biopsies of suspicious lesions. To enhance diagnostic precision both MCTU and URS
with focal samples should be included in the diagnostic procedure. The present
results add impact to current diagnostic guidelines.
PMID- 27611623
TI - Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time
Transcutaneous Measurement of Renal Function.
AB - Evaluation of renal function is crucial for a number of clinical situations.
Here, we reported a novel exogenous fluorescent marker (FITC-HPbetaCD) to real
time assess renal function by using a transcutaneous fluorescent detection
technique. FITC-HPbetaCD was designed based on the principle of renal clearance
of designed drugs. It displays favorable fluorescent properties, high
hydrophilicity, low plasma protein binding, and high stability in porcine liver
esterase as well as in plasma and nontoxicity. More importantly, FITC-HPbetaCD
can be efficiently and rapidly filtered by glomerulus and completely excreted
into urine without proximal tubular reabsorption or secretion in rat models.
Additionally, the marker was well-tolerated, with nearly 100% urinary recovery of
the given doses, and no metabolism were found. Relying on this novel kidney
function marker and transcutaneous devices, we demonstrate a rapid, robust, and
convenient approach for real-time assessing renal function without the need of
time-consuming blood and urine sample preparation. Our work provides a promising
tool for noninvasive real-time monitoring of renal function in vivo.
PMID- 27611624
TI - Older people and their care partners' experiences of living with mental health
needs: a focus on collaboration and cooperation.
AB - AIMS AND OBJECTIVES: To explore how older people living at home with mental
health needs and their care partners experienced the practices of collaboration
within and between services. BACKGROUND: Many healthcare strategies for community
mental health services for older people espouse a person-centred approach or
principles that are similar in focus. DESIGN: This study reports on the first
stage of a three-year action research project that focused on improving mental
health services for older people and their care partners living at home. Data
were collected through individual interviews. Twenty people were interviewed.
Data were analysed continuously and in parallel with data collection for the
identification of themes. RESULTS: We focus on two particular themes,
'acknowledgement, recognition and respect' and 'the prestige hierarchy of mental
illness in older people'. We highlight how older people and their care partners
experience discontinuities in their everyday interactions with nurses and care
workers and that this impacts on their experience of person-centred care.
CONCLUSIONS: Older people with mental health needs and their care partners need
high levels of energy to express their needs and have them met in a way that
reflects principles of partnership working. RELEVANCE TO CLINICAL PRACTICE:
Nurses and care workers need to consider how 'tasks' can be used as a vehicle for
creating emotional connections with service users. Service managers and leaders
need to consider the implications of discontinuities in care on service user,
care partner, nurses and care workers experiences.
PMID- 27611625
TI - Polysiloxane-Modified Tetraphenylethene: Synthesis, AIE Properties, and Sensor
for Detecting Explosives.
AB - Polysiloxane-modified tetraphenylethene (PTPESi) is successfully synthesized by
attaching tetraphenylethene (TPE) units onto methylvinyldiethoxylsiloxane and
subsequent polycondensation. Introducing polysiloxane into TPE has minimal effect
on the photophysical properties and aggregation-induced emission behavior of TPE.
The highest occupied and lowest unoccupied molecular orbital (HOMO and LUMO)
energy levels of PTPESi are located mainly on the tetraphenylethene moieties. The
fluorescence intensity and the half width of the emission peak of PTPESi before
and after annealing at 120 degrees C for 12 h are nearly the same, indicating
high thermal stability and morphological stability. In addition, use of PTPESi
film as a sensor toward the vapor-phase detection of explosives is also studied
and it displays quite high fluorescence quenching efficiency and good
reversibility.
PMID- 27611627
TI - Psychosocial distress in women diagnosed with gynecological cancer.
AB - Many women with gynecological cancer report psychosocial distress, and
clarification of the risks, vulnerabilities, and protective factors is required.
The aim of this study was to investigate the lived experience of gynecological
cancer patients and to understand the factors that underlie psychosocial
distress. Semi-structured interviews with seven women diagnosed with
gynecological cancer revealed the role of social support, or its absence,
selective withholding of information, and existential loneliness in women's
experience of distress. Social support provided a buffer against distress, while
feelings of alienation and being alone exacerbated distress. Interventions to
address these concerns may lead to improved quality of life for this patient
group.
PMID- 27611628
TI - Acceptability of vaccination against HIV: A mapping of Togolese people's
positions.
AB - In anticipation of a future HIV vaccine, we mapped the different personal
positions regarding HIV vaccination of people in Togo. In early 2014, 363 adults
indicated their willingness to receive a future HIV vaccine under different
conditions varying as a function of five factors: perceived susceptibility to
HIV, vaccine effectiveness, perceived severity of AIDS, vaccine cost, and
family's influence. We found five qualitatively different positions:
unconditional acceptance (49%), depends on cost/effectiveness ratio (20%),
depends on cost (18%), total indecision (10%), and complete reluctance (3%).
Accordingly, HIV vaccination strategies in Togo and elsewhere in Africa need to
be multifaceted and tailored.
PMID- 27611626
TI - Cardiovascular Risk in HIV-Infected and Uninfected Postmenopausal Minority Women:
Use of the Framingham Risk Score.
AB - OBJECTIVE: To characterize and compare cardiovascular disease (CVD) risk in HIV
infected and uninfected postmenopausal minority women using the Framingham Risk
Score (FRS) as an assessment measure. METHODS: A cross-sectional analysis was
performed in 152 (109 HIV+, 43 HIV-) subjects from an existing study cohort of
postmenopausal Hispanic and African American women. Data necessary to calculate
FRS and menopause features were retrieved by retrospective chart review.
Bivariate statistics was used to compare CVD risk factors. Multivariable linear
regression was used to determine factors associated with FRS in HIV-infected
women. RESULTS: The HIV-infected group was younger, less obese, and with lower
rates of diabetes versus controls. In a subset of age-matched participants,
median FRS did not differ between groups (14.6 [IQR = 9.1, 21.6] vs. 15.5 [IQR =
12.3, 22.1]; p = 0.73). Fourteen percent of HIV-infected women meeting criteria
for the low-risk FRS category (<10%) had a history of CVD, a similar rate as
controls. HIV-infected women at intermediate/high CVD risk had higher rates of
surgical menopause. According to 2013 clinical guidelines, more than half of HIV
infected women not prescribed statin therapy (52%) were eligible for treatment;
however, statin therapy was similarly under-prescribed in uninfected women.
CONCLUSIONS: In this study, CVD risk as assessed by the FRS was not significantly
different by HIV status. Performance of the FRS may be compromised in
postmenopausal HIV-infected minority women. HIV-infected and uninfected women may
be undertreated with statin therapy. Large longitudinal cohorts and inclusion of
subclinical measures of CVD are necessary to better characterize risk.
PMID- 27611629
TI - An exploration of appearance and health messages present in pregnancy magazines.
AB - This study explored appearance-related images and messages present in pregnancy
magazines (e.g. Fit Pregnancy, Pregnancy & Newborn, and Pregnancy Magazine). A
substantial portion of advertisements and articles promoted appearance-related
products or products for postpartum weight loss. Health messages and messages
related to diet and exercise were also present. Images also sexualized pregnant
women's bodies. Appearance-related messages aimed toward pregnant women may be
problematic and may contribute to body dissatisfaction in these women.
PMID- 27611630
TI - 'Strong is the new skinny': A content analysis of #fitspiration images on
Instagram.
AB - 'Fitspiration' is an online trend designed to inspire viewers towards a healthier
lifestyle by promoting exercise and healthy food. This study provides a content
analysis of fitspiration imagery on the social networking site Instagram. A set
of 600 images were coded for body type, activity, objectification and textual
elements. Results showed that the majority of images of women contained only one
body type: thin and toned. In addition, most images contained objectifying
elements. Accordingly, while fitspiration images may be inspirational for
viewers, they also contain a number of elements likely to have negative effects
on the viewer's body image.
PMID- 27611631
TI - Maladaptive coping in adults who have experienced early parental loss and grief
counseling.
AB - This study compares maladaptive coping, measured as substance use, behavioral
disengagement, self-blame, and emotional eating, among adults (>18 years) who
have experienced early parental loss ( N = 1465 women, N = 331 men) with non
bereaved controls ( N = 515 women, N = 115 men). We also compared bereaved adults
who received grief counseling ( N = 822 women, N = 190 men) with bereaved
controls who had not ( N = 233 women, N = 66 men). Bereaved adults reported
significantly more substance use, behavioral disengagement, and emotional eating
than non-bereaved adults. Counseling participants reported significantly more
substance use and self-blame than non-participants. Our results suggest that
early loss may negatively impact the development of adulthood coping.
PMID- 27611632
TI - Anxiety sensitivity and working memory capacity: Risk factors and targets for
health behavior promotion.
AB - Understanding the nature and influence of specific risk profiles is increasingly
important for health behavior promotion. The purpose of this article is to
document the value of two factors-anxiety sensitivity (AS) and working memory
capacity (WMC)-for enhancing risk for the initiation and/or maintenance of a
range of negative health behaviors. AS is a distress-related risk factor that
potentiates avoidance/coping motivations for negative health behaviors. Stress
provides the conditions for negative somatic and affective states, and AS
amplifies the aversiveness of these experiences and correspondingly hinders
adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by
decreasing the capacity to filter out current temptations, attenuating a focus on
longer-term goals and impairing the application of relevant coping skills at
times of stress. In this review, we provide conceptual models for the separate
roles of high AS and low WMC in negative health behaviors, review the influence
of these factors on specific health behavior exemplars (eating behaviors/obesity,
physical activity, smoking, alcohol use, and sleep promotion), provide
preliminary evidence for their value as independent treatment targets for health
behavior promotion, and encourage specific research directions in relation to
these variables.
PMID- 27611633
TI - Effects of variety and storage duration on the nutrient digestibility and the
digestible and metabolisable energy content of maize fed to growing pigs.
AB - The objective of this research was to determine the effects of variety and
storage duration on the nutrient digestibility and the digestible (DE) and
metabolisable (ME) energy content in maize when fed to growing pigs. Four maize
varieties (LS1, LS2, LS3 and LS4) were hand-harvested from the same growing area
in China in early October of 2012. The samples were sun dried to about 14%
moisture content and then stored in the warehouse of the Fengning Pig Experiment
Base at China Agricultural University for 0, 3 or 10 months. Twenty-four barrows
of about 33 kg body weight were used and allotted to a completely randomised
block design with four diets and six replicate pigs per diet. Pigs were
individually housed in metabolic crates. The four experimental diets were
formulated by mixing 96.8% of each variety of maize with 3.2% vitamins and
minerals. A 5-day collection period followed a 7-day diet acclimation period. The
results indicated that the DE and ME contents of maize and the apparent total
tract digestibility (ATTD) of organic matter (OM), dry matter, gross energy (GE),
neutral detergent fibre, acid detergent fibre (ADF), crude protein (CP) and ether
extract (EE) were significantly (p < 0.05) influenced by maize variety and
storage duration. With an extension of storage duration from 0 to 10 months, the
DE and ME of maize and the ATTD of OM, GE, ADF, CP and EE changed in a quadratic
manner (p < 0.05), and 3 months of storage exceeded 0 months of storage by 1.84%,
1.43%, 0.31%, 0.32%, 15.37%, 2.11% and 5.02%, respectively. The DE, ME of maize
and the ATTD of OM, GE, ADF, CP and EE decreased by 3.67%, 6.00%, 0.97%, 1.40%,
30.54%, 3.92% and 20.93%, respectively, at 10 months of storage compared to 3
months of storage. No interaction was observed between maize variety and storage
duration in DE and ME contents in maize. In conclusion, under the conditions of
this study, most of the nutrient digestibility and the DE and ME contents of
maize increased from 0 to 3 months and decreased from 3 to 10 months.
PMID- 27611635
TI - Formation of Environmentally Persistent Free Radicals on alpha-Al2O3.
AB - Metal oxides exhibit catalytic activity for the formation of environmentally
persistent free radicals (EPFRs). Here, we investigate, via first-principles
calculations, the activity of alumina alpha-Al2O3(0001) surface toward formation
of phenolic EPFRs, under conditions relevant to cooling down zones of combustion
systems. We show that, molecular adsorption of phenol on alpha-Al2O3(0001)
entails binding energies in the range of -202 kJ/mol to -127 kJ/mol. The
dehydroxylated alumina catalyzes the conversion of phenol into its phenolate
moiety with a modest activation energy of 48 kJ/mol. Kinetic rate parameters,
established over the temperature range of 300 to 1000 K, confirm the formation of
the phenolate as the preferred pathways for the adsorption of phenol on alumina
surfaces, corroborating the role of particulate matter in the cooling down zone
of combustion systems in the generation of EFPRs.
PMID- 27611634
TI - Non-targeted metabolite profiling highlights the potential of strawberry leaves
as a resource for specific bioactive compounds.
AB - BACKGROUND: The non-edible parts of horticultural crops, such as leaves, contain
substantial amounts of valuable bioactive compounds which are currently only
little exploited. For example, strawberry (Fragaria * ananassa) leaves may be a
promising bioresource for diverse health-related applications. However, product
standardization sets a real challenge, especially when the leaf material comes
from varying cultivars. The first step towards better quality control of berry
fruit leaf-based ingredients and supplements is to understand metabolites present
and their stability in different plant cultivars, so this study surveyed the
distribution of potentially bioactive strawberry leaf metabolites in six
different strawberry cultivars. Non-targeted metabolite profiling analysis using
LC/qTOF-ESI-MS with data processing via principal component analysis and k-means
clustering analysis was utilized to examine differences and commonalities between
the leaf metabolite profiles. RESULTS: Quercetin and kaempferol derivatives were
the dominant flavonol groups in strawberry leaves. Previously described and novel
caffeic and chlorogenic acid derivatives were among the major phenolic acids. In
addition, ellagitannins were one of the distinguishing compound classes in
strawberry leaves. In general, strawberry leaves also contained high levels of
octadecatrienoic acid derivatives, precursors of valuable odour compounds.
CONCLUSION: The specific bioactive compounds found in the leaves of different
strawberry cultivars offer the potential for the selection of optimized leaf
materials for added-value food and non-food applications. (c) 2016 Society of
Chemical Industry.
PMID- 27611636
TI - The body of knowledge in thanatology: An outline.
AB - The Association for Death Education and Counseling has updated its articulation
of the body of knowledge in the field of thanatology. In doing so it has
relinquished the use of a matrix format in favor of a more serviceable outline
containing three major sections: Arenas of Thanatology, Practice Considerations
for Professionals in the Field, and Contextual and Theoretical Considerations.
Accompanying the outline is a new commentary on the state of the field itself,
along with an annotated bibliography of recent relevant publications.
PMID- 27611637
TI - Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized
Controlled Pilot Study.
AB - RATIONALE: Sevoflurane improves gas exchange, and reduces alveolar edema and
inflammation in preclinical studies of lung injury, but its therapeutic effects
have never been investigated in acute respiratory distress syndrome (ARDS).
OBJECTIVES: To assess whether sevoflurane would improve gas exchange and
inflammation in ARDS. METHODS: We did a parallel, open-label single-center
randomized controlled trial at three intensive care units from a French
university hospital between April 2014 and February 2016. Adult patients were
randomized within 24 hours of moderate-to-severe ARDS onset to receive either
intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome
was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and
plasma levels of cytokines and soluble form of the receptor for advanced
glycation end-products, and safety. Investigators who did the analyses were
masked to group allocation. Analysis was by intention to treat. MEASUREMENTS AND
MAIN RESULTS: Twenty-five patients were assigned to the sevoflurane group and 25
to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane
group than in the midazolam group (mean +/- SD, 205 +/- 56 vs. 166 +/- 59,
respectively; P = 0.04). There was a significant reduction over time in cytokines
and soluble form of the receptor for advanced glycation end-products levels in
the sevoflurane group, compared with the midazolam group, and no serious adverse
event was observed with sevoflurane. CONCLUSIONS: In patients with ARDS, use of
inhaled sevoflurane improved oxygenation and decreased levels of a marker of
epithelial injury and of some inflammatory markers, compared with midazolam.
Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).
PMID- 27611638
TI - Emergency Department Management of Patients With Febrile Neutropenia: Guideline
Concordant or Overly Aggressive?
AB - OBJECTIVES: The Infectious Diseases Society of America and the American Society
of Clinical Oncology recommend risk stratification of patients with febrile
neutropenia (FN) and discharge with oral antibiotics for low-risk patients. We
studied guideline concordance and clinical outcomes of FN management in our
emergency department (ED). METHODS: Our urban, tertiary care teaching hospital
provides all emergency and inpatient services to a large comprehensive cancer
center. We performed a structured chart review of all FN patients seen in our ED
from January 2010 to December 2014. Using electronic medical records, we
identified all visits by patients with fever and an absolute neutrophil count of
<1000 cells/mm3 and then included only patients without a clear source of
infection. Following national guidelines, we classified patients as low or high
risk and assessed guideline concordance in disposition and parenteral versus oral
antibiotic therapy by risk category as our main outcome measure. RESULTS: Of 173
qualifying visits, we classified 44 (25%) as low risk and 129 (75%) as high risk.
Management was guideline concordant in 121 (70%, 95% confidence interval [CI] =
63% to 77%). Management was guideline discordant in 43 (98%, 95% CI = 88% to
100%) of low-risk patients versus 9 (7%, 95% CI = 3% to 13%) of high-risk
patients (relative risk [RR] = 14, 95% CI = 7.5 to 26). Of 52 guideline
discordant cases, 36 (83%, 95% CI = 72% to 93%) involved low-risk cases with
treatment that was more aggressive than recommended. CONCLUSIONS: Guideline
concordance was low among low-risk patients, with management tending to be more
aggressive than recommended. Unless data emerge that undermine the guidelines, we
believe that many of these hospitalizations and parenteral antibiotic regimens
can be avoided, decreasing the risks associated with hospitalization, while
improving antibiotic stewardship and patient comfort.
PMID- 27611639
TI - N-nitrosodimethylamine (NDMA) formation during ozonation of N,N-dimethylhydrazine
compounds: Reaction kinetics, mechanisms, and implications for NDMA formation
control.
AB - Compounds with N,N-dimethylhydrazine moieties ((CH3)2N-N-) form N
nitrosodimethylamine (NDMA) during ozonation, but the relevant reaction chemistry
is hitherto poorly understood. This study investigated the reaction kinetics and
mechanisms of NDMA formation during ozonation of unsymmetrical dimethylhydrazine
(UDMH) and daminozide (DMZ) as structural model N,N-dimethylhydrazine compounds.
The reaction of ozone with these NDMA precursor compounds was fast, and kO3 at pH
7 was 2 * 106 M-1 s-1 for UDMH and 5 * 105 M-1 s-1 for DMZ. Molar NDMA yields
(i.e., Delta[NDMA]/Delta[precursor] * 100) were 84% and 100% for UDMH and DMZ,
respectively, determined at molar ozone dose ratio ([O3]0/[precursor]0) of >=4 in
the presence of tert-butanol as hydroxyl radical (OH) scavenger. The molar NDMA
yields decreased significantly in the absence of tert-butanol, indicating OH
formation and its subsequent reaction with the parent precursors forming
negligible NDMA. The kOH at pH 7 was 4.9 * 109 M-1 s-1 and 3.4 * 109 M-1 s-1 for
UDMH and DMZ, respectively. Reaction mechanisms are proposed in which an ozone
adduct is formed at the nitrogen next to N,N-dimethylamine which decomposes via
homolytic and heterolytic cleavages of the -N+-O-O-O- bond, forming NDMA as a
final product. The heterolytic cleavage pathway explains the significant OH
formation via radical intermediates. Overall, significant NDMA formation was
found to be unavoidable during ozonation or even O3/H2O2 treatment of waters
containing N,N-dimethylhydrazine compounds due to their rapid reaction with ozone
forming NDMA with high yield. Thus, source control or pre-treatment of N,N
dimethylhydrazine precursors and post-treatment of NDMA are proposed as the
mitigation options.
PMID- 27611640
TI - Effect of titanium dioxide nanoparticles on copper toxicity to Daphnia magna in
water: Role of organic matter.
AB - Inevitably released into natural water, titanium dioxide nanoparticles (nano
TiO2) may affect the toxicity of other contaminants. Ubiquitous organic matter
(OM) may influence their combined toxicity, which has been rarely reported. This
study investigated the effect of nano-TiO2 on Cu toxicity to Daphnia magna and
the role of OM (dissolved or particle surface bound) in inducing combined
effects. The effect of nano-TiO2 on heavy metal accumulation depended on the
adsorption capacity for heavy metals of nano-TiO2 and the uptake of nano-TiO2
metal complexes by organisms. Nano-TiO2 significantly decreased Cu accumulation
in D. magna, but the reducing effect of nano-TiO2 was eliminated in the presence
of humic acid (HA, a model OM). In the Cu and HA solution, nano-TiO2 slightly
affected the bioavailability of Cu2+ and Cu-HA complexes and thus slightly
influenced Cu toxicity. The nanoparticle surface-bound HA reduced the effect of
nano-TiO2 on the speciation of the accumulated Cu; therefore, the combined
effects of nano-TiO2 and Cu on biomarkers similarly weakened. HA-altered Cu
speciation may be the main factor responsible for the influence of HA on the
combined effects of nano-TiO2 and Cu. This study provides insights into the
combined effects of nano-TiO2 and heavy metals in natural water.
PMID- 27611641
TI - Simultaneous analysis of neutral monosaccharides, fatty acids and cholesterol as
biomarkers from a drop of blood.
AB - AIM: We have developed a method for simultaneous monitoring of more biomarkers
from three different classes of compounds by simultaneous analysis of neutral
monosaccharides, fatty acids (FAs) and cholesterol as their per-O-methylated
derivatives from a drop of blood by GC-MS. This work is a development of our
previous results about analysis of neutral monosaccharides from a drop of blood.
METHODS & RESULTS: The simultaneous per-O-methylation was obtained by methylation
in one step with methyl iodide and NaOH in DMSO. The per-O-methylated derivatives
were separated in one chromatogram. The quantitative analysis was reproducible
for five monosaccharides, 22 FAs and cholesterol. The results of this method were
compared with those of the enzymatic methods using commercial kits. CONCLUSION:
This method can avoid the saponification of the FA methyl esters and can analyze
for the first time simultaneously neutral monosaccharides, FAs and cholesterol
from a drop of blood.
PMID- 27611642
TI - Tapentadol Prolonged Release for Chronic Pain: A Review of Clinical Trials and 5
Years of Routine Clinical Practice Data.
AB - Tapentadol prolonged release (PR) for the treatment of moderate to severe chronic
pain combines 2 modes of action. These are MU-opioid receptor agonism and
noradrenaline reuptake inhibition in a single molecule that allow higher
analgesic potency through modulation of different pharmacological targets within
the pain transmitting systems. At the same time, this can also serve as a clue
for modulation of different pain-generating mechanisms according to nociceptive,
neuropathic, or mixed pain conditions. Tapentadol PR has now been on the market
for 5 years, with over 4.6 million people treated worldwide. A panel of pain
specialists convened in Germany to review the clinical program and to discuss the
role of tapentadol PR in the management of chronic pain. The clinical study
program demonstrated effective and generally well-tolerated treatment for up to 2
years in a broad range of chronic pain conditions, including those with
neuropathic pain components. This was confirmed in routine clinical practice
observations. Head-to-head studies with World Health Organization (WHO) III
opioids such as oxycodone controlled release and oxycodone/naloxone PR showed at
least comparable pain relief in the treatment of moderate-to-severe
musculoskeletal pain. Rotation from poorly tolerated WHO III opioids to
tapentadol PR provided effective pain relief and better symptom control for
musculoskeletal pain compared to previous medication. Functionality, health
status and quality of life also improved under tapentadol PR treatment. The
gastrointestinal tolerability profile was more favorable compared to other tested
WHO III opioids. Tapentadol PR has a good safety profile and no evidence of
acquired tolerance from the long-term data so far collected. Overall, tapentadol
PR represents an effective and generally well-tolerated alternative to
"classical" opioidergic drugs.
PMID- 27611643
TI - Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term
Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and
Phenotypic Plasticity.
AB - Variations in egg incubation temperatures can have acute or long-term effects on
gene transcription in avian species. Altered gene expression may, in turn, affect
muscle traits in poultry and indirectly influence commercial production. To
determine how changes in eggshell temperature affect gene expression, incubation
temperatures were varied [36.8 degrees C (low), 37.8 degrees C (control), 38.8
degrees C (high)] at specific time periods reflecting two stages of myogenesis
[embryonic days (ED) 7-10 and 10-13]. Gene expression was compared between
interventions and matching controls by microarrays in broiler breast muscle at
ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature
(H10DeltaC) resulted in 1370 differentially expressed genes (DEGs) in embryos.
Ingenuity pathway analysis revealed temporary activation of cell maintenance,
organismal development, and survival ability genes, but these effects were not
maintained in adults. Late high incubation temperature (ED10-13) (H13DeltaC) had
slightly negative impacts on development of cellular components in embryos, but a
cumulative effect was observed in adults, in which tissue development and
nutrition metabolism were affected. Early low incubation temperature (L10DeltaC)
produced 368 DEGs, most of which were down-regulated and involved in
differentiation and formation of muscle cells. In adults, this treatment down
regulated pathways of transcriptional processes, but up-regulated cell
proliferation. Late low temperature incubation (L13DeltaC) produced 795 DEGs in
embryos, and activated organismal survival and post-transcriptional regulation
pathways. In adults this treatment activated cellular and organ development,
nutrition and small molecule activity, and survival rate, but deactivated size of
body and muscle cells. Thermal interventions during incubation initiate immediate
and delayed transcriptional responses that are specific for timing and direction
of treatment. Interestingly, the transcriptional response to transiently
decreased incubation temperature, which did not affect the phenotypes, prompts
compensatory effects reflecting resilience. In contrast, higher incubation
temperature triggers gene expression and has long-term effects on the phenotype.
These mechanisms of considerable phenotypic plasticity contribute to the
biodiversity and broaden the basis for managing poultry populations.
PMID- 27611644
TI - Interaction studies of human prion protein (HuPrP109-111: methionine-lysine
histidine) tripeptide model with transition metal cations.
AB - In the present study, the coordination bonds between the Methionine-Lysine
Histidine (Ac-MKH-NHMe) tripeptide model associated with the fifth metal binding
site, which triggers the beta-sheet formation of human prion protein and the
divalent metal cations such as Mn(2+), Cu(2+) and Zn(2+) were studied using B3LYP
and M052X levels of theory with LANL2DZ basis set. For each transition divalent
metal cation, three different coordination modes (4N, 3NO, and 2NSO) were
analyzed. The present result reveals that overall structural parameters of MKH
model tripeptide are altered due to the interaction of divalent metal cations.
Among these three coordination modes, the 4N-M(2)(+) and 4N2O-Mn(2+) complexes
are found to have the larger interaction energy, MIA and deformation energies.
The triply deprotonated coordination mode of the Ac-MKH-NHMe tripeptide transfers
more amount of charge to the divalent metal cations than the dually and singly
deprotonated complexes. Furthermore, the atoms in molecules (AIM) topological
analysis confirm that, the interaction between the metal cations Mn(2+), Cu(2+)
and Zn(2+) and Ac-MKH-NHMe tripeptide are electrostatic dominant and the
coordination modes with triply deprotonation states possess larger electron
density at their BCP corresponding to their coordination bonds. The electrostatic
potential difference maps of the most stable 4N-M(2+) (M(2+)=Cu(2+) and Zn(2+))
and 4N2O-Mn(2+) reveals that, as the ionic radii of the metal ion increases, the
delocalization charges localized on the metal cations are found to be decreased.
The Infra-red stretching frequencies of NH, CH, and CH2 groups of each
coordination complexes are observed with shift in their stretching frequencies.
From these observations we conclude that, the transition divalent metal cations
binding in 4N coordination mode will induce more conformational changes of the
Prion protein.
PMID- 27611645
TI - Hydration of ligands of influenza virus neuraminidase studied by the fragment
molecular orbital method.
AB - The fragment molecular orbital (FMO) method was applied to quantum chemical
calculations of neuramic acid, the natural substrate of the influenza virus
neuraminidase, and two of its competitive inhibitors, Oseltamivir (Tamiful((r)))
and Zanamivir (Relenza((r))), to investigate their hydrated structures and
energetics. Each of the three ligands was immersed in an explicit water solvent,
geometry-optimized by classical MM and QM/MM methods, and subjected to FMO
calculations with 2-, 3-, and 4-body corrections under several fragmentation
options. The important findings were that QM/MM optimization was preferable to
obtain reliable hydrated structures of the ligands, that the 3-body correction
was important for quantitative evaluation of the solvation energy, and that the
dehydration effect was most remarkable near the hydrophobic sections of the
ligands. In addition, the hydration energy calculated by the explicit solvent was
compared with the hydration free energy calculated by the implicit solvent via
the Poisson-Boltzmann equation, and the two showed a fairly good correlation.
These findings will serve as useful information for rapid drug design.
PMID- 27611646
TI - Analysis of amphetamine and methamphetamine in municipal wastewater influent and
effluent using weak cation-exchange SPE and LC-MS/MS.
AB - Amphetamine and methamphetamine are emerging contaminants-those for which no
regulations currently require monitoring or public reporting of their presence in
our water supply. In this research, a protocol for weak cation-exchange (WCX) SPE
coupled with LC-MS/MS was developed for determination of emerging contaminants
amphetamine and methamphetamine in a complex wastewater matrix. Gradient LC
parameters were adjusted to yield baseline separation of methamphetamine from
other contaminants. Methamphetamine-D5 was used as the internal standard (IS) to
compensate for sample loss during SPE and for signal loss during MS (matrix
effects). Recoveries were 102.1 +/- 7.9% and 99.4 +/- 4.0% for amphetamine and
methamphetamine, respectively, using WCX sorbent. Notably, methamphetamine was
determined to be present in wastewater influent at each sampling date tested.
Amphetamine was present in wastewater influent on two of four sampling dates.
Amphetamine concentrations ranged from undetectable to 86.4 ng/L in influent, but
it was undetectable in wastewater effluent. Methamphetamine was detected in
influent at concentrations ranging from 27.0-60.3 ng/L. Methamphetamine
concentration was reduced but incompletely removed at this facility. Although
absent in one post-UV effluent sample, concentrations of methamphetamine ranged
from 10.8-14.8 ng/L.
PMID- 27611647
TI - Immunohistochemical Localization of Luteinizing Hormone Receptor in the Cyclic
Gilt Ovary.
AB - Luteinizing hormone receptor (LHR) is a specific membrane receptor on the
granulosa and theca cells that bind to luteinizing hormone (LH), resulting in
androgen and progesterone production. Hence, the regulation of LHR expression is
necessary for follicle maturation, ovulation and corpus luteum formation. We
examined the immunolocalization of LHR in cyclic gilt ovaries. The ovaries were
obtained from 21 gilts aged 326.0 +/- 38.7 days and weighing 154.6 +/- 15.7 kg.
The ovarian tissues were incubated with rabbit anti-LHR polyclonal antibody. The
follicles were categorized as primordial, primary, preantral and antral
follicles. Ovarian phase was categorized as either follicular or luteal phases.
The immunolocalization of LHR was clearly expressed in primary, preantral and
antral follicles. LHR immunostaining was detected in the cytoplasm of granulosa,
theca interna and luteal cells. LHR immunostaining was evaluated using imaging
software. LHR immunostaining in the theca interna cells in antral follicles was
almost twice as intense as that in preantral follicles (65.4% versus 38.3%, P <
0.01). LHR immunostaining was higher in the follicular phase than in the luteal
phase (58.6% versus 45.2%, P < 0.05). In conclusion, the expression of LHR in the
theca interna cells of antral follicles in the follicular phase was higher than
in the luteal phase. The expression of LHR in all types of the follicles
indicates that LHR may impact follicular development from the primary follicle
stage onwards.
PMID- 27611648
TI - Site-Targeted Interfacial Solid-Phase Chemistry: Surface Functionalization of
Organic Monolayers via Chemical Transformations Locally Induced at the Boundary
between Two Solids.
AB - Effective control of chemistry at interfaces is of fundamental importance for the
advancement of methods of surface functionalization and patterning that are at
the basis of many scientific and technological applications. A conceptually new
type of interfacial chemical transformations has been discovered, confined to the
contact surface between two solid materials, which may be induced by exposure to
X-rays, electrons or UV light, or by the application of electrical bias. One of
the reacting solids is a removable thin film coating that acts as a
reagent/catalyst in the chemical modification of the solid surface on which it is
applied. Given the diversity of thin film coatings that may be used as solid
reagents/catalysts and the lateral confinement options provided by the use of
irradiation masks, conductive AFM probes or stamps, and electron beams in such
solid-phase reactions, this approach is suitable for precise targeting of
different desired chemical modifications to predefined surface sites spanning the
macro- to nanoscale.
PMID- 27611649
TI - Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic
environment.
AB - Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the
surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it
modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis
and is strongly associated with poor clinical prognosis. We have carried out the
first investigation into the effect of polySia expression on the behaviour of
cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of
polysialylation and associated tumour cell migration and cell adhesion were
studied in hypoxia, along with effects on cell survival and the potential role of
HIF-1. Our findings provide the first evidence that polySia expression sustains
migratory capacity and is associated with tumour cell survival in hypoxia.
Initial mechanistic studies indicate a potential role for HIF-1 in sustaining
polySia-mediated migratory capacity, but not cell survival. These data add to the
growing body of evidence pointing to a crucial role for the
polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide
the first evidence to suggest that polySia is associated with an aggressive
phenotype in tumour hypoxia. These results have significant potential
implications for polyST inhibition as an anti-metastatic therapeutic strategy and
for targeting hypoxic cancer cells.
PMID- 27611652
TI - Sex and Intimacy after Stroke.
AB - PROBLEM: The sequelae of a stroke can negatively affect sex and intimacy for
survivors and their partners. PURPOSE: This clinical article offers practical
evidence-based recommendations for nurses to use in advising couples who may be
experiencing sexual problems due to decreased desire, erectile dysfunction,
vaginal dryness, paraparesis, pain, spasticity, fatigue, aphasia, concrete
thinking, emotional lability, shame, embarrassment, fear, depression, or
neurogenic bladder. KEY FINDINGS AND CLINICAL RELEVANCE: Recent research and
clinical articles show that intimacy and sexual concerns are often ignored by the
rehabilitation team, yet research shows that couples want information to assist
them to maintain their sexual relationships. Using the PLISSIT model to address
sexual concerns, nurses can facilitate discussions to aid couples toward improved
sexual function and quality of life.
PMID- 27611651
TI - Familial resemblances in blood leukocyte DNA methylation levels.
AB - Epigenetic factors such as DNA methylation are DNA alterations affecting gene
expression that can convey environmental information through generations. Only a
few studies have demonstrated epigenetic inheritance in humans. Our objective is
to quantify genetic and common environmental determinants of familial
resemblances in DNA methylation levels, using a family based sample. DNA
methylation was measured in 48 French Canadians from 16 families as part of the
GENERATION Study. We used the Illumina HumanMethylation450 BeadChip array to
measure DNA methylation levels in blood leukocytes on 485,577 CpG sites.
Heritability was assessed using the variance components method implemented in the
QTDT software, which partitions the variance into polygenic (G), common
environmental (C), and non-shared environmental (E) effects. We computed maximal
heritability, genetic heritability, and common environmental effect for all
probes (12.7%, 8.2%, and 4.5%, respectively) and for statistically significant
probes (81.8%, 26.9%, and 54.9%, respectively). Higher maximal heritability was
observed in the Major Histocompatibility Complex region on chromosome 6. In
conclusion, familial resemblances in DNA methylation levels are mainly
attributable to genetic factors when considering the average across the genome,
but common environmental effect plays an important role when considering
statistically significant probes. Further epigenome-wide studies on larger
samples combined with genome-wide genotyping studies are needed to better
understand the underlying mechanisms of DNA methylation heritability.
PMID- 27611653
TI - Cytotoxic and Anti-inflammatory Sesquiterpenes from Ainsliaea henryi.
AB - Three new sesquiterpenoids, 4alpha-hydroxyeudesm-11(13)-en-12-yl 3
methylbutanoate (1), diaspanolide E (2), and (13alpha)-germacra-1(10),4-dien
12,8alpha-olid-15-oic acid (3), along with eight known sesquiterpenoids (4 - 11),
were isolated from the aerial parts of Ainsliaea henryi. The chemical structures
of compounds 1 - 3 were elucidated by spectroscopic analysis (1D-, 2D-NMR, MS and
HR/MS). All isolates were evaluated for their inhibitory activities against
nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophage
cells. Compound 10 exhibited significantly inhibition against NO release with an
IC50 value of 6.54 +/- 0.16 MUm. Also, all isolated compounds were tested for
cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among
which compound 5 significantly inhibited the proliferation of MGC803 cell lines
with an IC50 value of 2.2 +/- 0.2 MUm.
PMID- 27611654
TI - MRI Findings in Patients With Leukemia and Positive CSF Cytology: A Single
Institution 5-Year Experience.
AB - OBJECTIVE: The purposes of this study were to describe the spectrum of MRI
findings and determine the prognostic role of MRI in adults with acute leukemia
with positive CSF cytology. MATERIALS AND METHODS: In this retrospective study of
34 patients (19 women, 15 men; mean age, 51 years; range, 18-72 years) treated
for CNS leukemia between 2006 and 2011, 31 (91%) contrast-enhanced brain and 14
(41%) spine MRI studies were reviewed by two radiologists to note patterns of
enhancement. Interobserver agreement and correlation of enhancement with outcome
were analyzed. RESULTS: MRI showed abnormal findings in 25 patients (74%).
Pachymeningeal enhancement (n = 9/31, 29%), leptomeningeal enhancement (n = 6/31,
19%), cranial nerve enhancement (n = 9/31, 29%), masslike enhancement (n = 3/31,
10%), and spinal meningeal enhancement (n = 10/14, 71%) were identified. There
was strong interobserver agreement (kappa = 0.906). Survival rates were shorter
to a statistically significant degree with pachymeningeal enhancement (median, 7
months; interquartile range [IQR], 5-8 months versus median, 26 months; IQR, 15
months to not reached; p = 0.004) and two or more sites of enhancement (median, 8
months; IQR, 3-13 months versus median, 19 months; IQR, 9 months to not reached;
p = 0.046). CONCLUSION: Brain or spine MRI examinations (or both) showed abnormal
findings in nearly three-fourths of adults with acute leukemia with positive CSF
cytology who were imaged for neurologic symptoms. Pachymeningeal enhancement and
two or more sites of brain involvement were associated with shorter survival.
PMID- 27611655
TI - Prevalence and Risk Factors Associated with Hemoparasites in Cattle and Goats at
the Edge of Kibale National Park, Western Uganda.
AB - Livestock production is a major sector of the Ugandan economy. Ugandan ruminant
livestock (principally cattle and goats) are susceptible to hemoparasites that
can cause serious clinical disease and production losses. Kibale National Park,
in western Uganda, is a protected forest ecosystem surrounded by small-scale
farms where cattle and goats are raised. We conducted a cross-sectional study of
cattle and goats in this area and diagnosed hemoparasite infections by
microscopy. We collected data on animal characteristics and management practices
to assess risk factors associated with infection. We studied 186 cattle and 317
goats from 20 villages, including 16 villages directly adjacent to Kibale and 4
villages >=3 km from the park boundary. Hemoparasites detected in cattle and
goats were of the genera Theileria, Anaplasma, and Trypanosoma with a prevalence
of 15.1%, 1.6%, and 4.3% respectively in cattle, and 10%, 6.0%, and 0.0%,
respectively in goats. Trypanosomes infected approximately 8% of cattle in
villages bordering Kibale but were never detected in cattle in "control" villages
>=3 km from the park. Trypanosomes were approximately 7 times more likely to
infect animals in households that did not provide veterinary care to their
animals than in households that provided routine veterinary care. Within cattle,
Theileria infections were approximately 7 times more likely to occur in cross
bred cattle than in indigenous pure breeds. Anaplasma infections were
approximately 3.5 times more likely to occur in cattle than in goats (no goats
were diagnosed with Trypanosoma infection). These data suggest that proximity to
the park, provision of veterinary care, and breed are significant risk factors
for hemoparasites in this population of ruminants, and that, in general, cattle
are more susceptible than goats.
PMID- 27611656
TI - Chromogranin A as biomarker in diabetes.
AB - Chromogranin A (CgA) is an established plasma marker of neuroendocrine tumors and
has been suggested to also have a role as biomarker in other diseases. Whether
CgA has any role as biomarker in diabetes is, however, unresolved, but its
widespread distribution in the secretory granules in endocrine tissues including
beta cells and alpha cells in pancreas, and the metabolic effects of its peptide
fragments suggest that CgA may play a pathophysiological role in diabetes, and
thus also be a potential diabetes biomarker. In this review, we summarize the
available information on CgA and some of its functional post-translational
cleavage products in diabetes, followed by a discussion of its potential as a
plasma marker in diabetes and the methodological concerns involved.
PMID- 27611657
TI - Effect of a Multi-Nutrient Over-the-Counter Supplement on Changes in Metabolic
Rate and Markers of Lipolysis.
AB - Using a prospective, randomized, double-blind, crossover study design, fifteen
healthy male (n = 8) and female (n = 7) participants (mean +/- standard deviation
(SD): 28.3 +/- 6.1 yr, 176.3 +/- 11.4 cm, 89.8 +/- 21.7 kg, 28.5 +/- 4.8 kg/m2)
completed this study. Two testing sessions occurred after an overnight fast and
refraining from physical exercise. Prior to and 60, 120, and 180 minutes after
single dose ingestion of placebo (PLA) or a Thermogenic Supplement (TS), visual
analog scales (VAS), resting metabolic rate (VO2), and venous blood were
collected. Resting heart rate and blood pressures were collected before, and 30,
60, 90, 120, 150 and 180 minutes after PLA or TS ingestion. Significant group *
time interactions were found for VO2 with TS experiencing significant (p < 0.05)
increases 60 and 120 minutes after ingestion. Respiratory quotient values tended
to be lower 180 minutes (p = 0.07) after TS ingestion. TS group reported
increased energy 60 minutes (p < 0.05) after ingestion. No interactions were
reported for resting heart rate or blood pressure. Significant within-group
reductions in systolic blood pressure were noted for PLA, while resting heart
rates were significantly lower in TS 30 and 60 minutes after ingestion. An
interaction for epinephrine (p = 0.02) was found, while no changes were reported
for norepinephrine and dopamine. Dependent t-tests using area under the curve
calculations revealed higher AUC values for epinephrine in TS compared to PLA (p
= 0.001). In conclusion, ingestion of a single dose of TS increased oxygen
consumption, epinephrine and energy levels, while substrate oxidation tended to
change in comparison to a placebo. No adverse responses were reported.
PMID- 27611658
TI - Single-step biological fabrication of colloidal silver nanoparticles using
Hugonia mystax: larvicidal potential against Zika virus, dengue, and malaria
vector mosquitoes.
AB - Mosquito control is facing key challenges, including outbreaks of new arbovirus
threats. We proposed an eco-friendly synthesis of silver nanoparticles (AgNPs)
employing a low-cost extract of Hugonia mystax. AgNPs were specified by UV, XRD,
FTIR and EDX spectroscopy, SEM and TEM. AgNPs were more toxic to Anopheles
stephensi, Aedes aegypti, and Culex quinquefasciatus larvae (LC50: 14.45, 15.86,
and 17.46 MUg/mL) if compared to aquatic biocontrol organisms Gambusia affinis,
Diplonychus indicus, and Anisops bouvieri (LC50: 2567.15, 1075.16, and 829.63
MUg/ml). Overall, we shed light on the mosquito larvicidal efficacy of H. mystax,
a possible biological resource for low-cost fabrication of AgNPs.
PMID- 27611659
TI - Trauma management in Homer's Iliad.
AB - Homer's Iliad is one of the highest intellectual products of the early ancient
Greek civilisation. A plethora of medical information lies within Iliad's 24
rhapsodies, and a total of 147 injuries are described. The present study records
and evaluates all cases of trauma management included in this epic poem. Not only
Iliad's original text but also all myths related to Iliad from the five-volume
Greek Mythology by Ioannis Kakridis were meticulously studied to locate the
injured person, the type of trauma, the care provider and the type of given care
as well as the outcome of each case. A total of 21 cases were found and evaluated
with a 5% mortality rate. The majority of these injuries were caused by an arrow
(43%) and were located to the upper extremity (43%). Injuries of the head, neck
and trunk were not treated as all of them were lethal. Many of the recorded
trauma management techniques can be correlated to modern medicine. Furthermore,
the role and skills of military doctors and paramedics, mentioned by Homer, is
discussed.
PMID- 27611661
TI - Involvement of tyrosinase-related protein 1 gene in the light brown plumage
phenotype of Falco cherrug.
PMID- 27611660
TI - Pten and EphB4 regulate the establishment of perisomatic inhibition in mouse
visual cortex.
AB - Perisomatic inhibition of pyramidal neurons is established by fast-spiking,
parvalbumin-expressing interneurons (PV cells). Failure to assemble adequate
perisomatic inhibition is thought to underlie the aetiology of neurological
dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we
show that in mouse visual cortex, strong perisomatic inhibition does not develop
if PV cells lack a single copy of Pten. PTEN signalling appears to drive the
assembly of perisomatic inhibition in an experience-dependent manner by
suppressing the expression of EphB4; PV cells hemizygous for Pten show an ~2-fold
increase in expression of EphB4, and over-expression of EphB4 in adult PV cells
causes a dismantling of perisomatic inhibition. These findings implicate a
molecular disinhibitory mechanism driving the establishment of perisomatic
inhibition whereby visual experience enhances Pten signalling, resulting in the
suppression of EphB4 expression; this relieves a native synaptic repulsion
between PV cells and pyramidal neurons, thereby promoting the assembly of
perisomatic inhibition.
PMID- 27611662
TI - Global Health, Geographical Contingency, and Contingent Geographies.
AB - Health geography has emerged from under the "shadow of the medical" to become one
of the most vibrant of all the subdisciplines. Yet, this success has also meant
that health research has become increasingly siloed within this subdisciplinary
domain. As this article explores, this represents a potential lost opportunity
with regard to the study of global health, which has instead come to be dominated
by anthropology and political science. Chief among the former's concerns are
exploring the gap between the programmatic intentions of global health and the
unintended or unanticipated consequences of their deployment. This article
asserts that recent work on contingency within geography offers significant
conceptual potential for examining this gap. It therefore uses the example of
alcohol taxation in Botswana, an emergent global health target and tool, to
explore how geographical contingency and the emergent, contingent geographies
that result might help counter the prevailing tendency for geography to be side
stepped within critical studies of global health. At the very least, then, this
intervention aims to encourage reflection by geographers on how to make explicit
the all-too-often implicit links between their research and global health debates
located outside the discipline.
PMID- 27611663
TI - Black Edens, country Eves: Listening, performance, and black queer longing in
country music.
AB - This article explores Black queer country music listening, performance, and
fandom as a source of pleasure, nostalgia, and longing for Black listeners.
Country music can be a space for alliance and community, as well as a way of
accessing sometimes repressed cultural and personal histories of violence:
lynching and other forms of racial terror, gender surveillance and disciplining,
and continued racial and economic segregation. For many Black country music
listeners and performers, the experience of being a closeted fan also fosters an
experience of ideological hailing, as well as queer world-making. Royster
suggests that through Black queer country music fandom and performance, fans
construct risky and soulful identities. The article uses Tina Turner's solo
album, Tina Turns the Country On! (1974) as an example of country music's power
as a tool for resistance to racial, sexual, and class disciplining.
PMID- 27611664
TI - Quantitation of Murine Stroma and Selective Purification of the Human Tumor
Component of Patient-Derived Xenografts for Genomic Analysis.
AB - Patient-derived xenograft (PDX) mouse models are increasingly used for
preclinical therapeutic testing of human cancer. A limitation in molecular and
genetic characterization of PDX tumors is the presence of integral murine stroma.
This is particularly problematic for genomic sequencing of PDX models. Rapid and
dependable approaches for quantitating stromal content and purifying the
malignant human component of these tumors are needed. We used a recently
developed technique exploiting species-specific polymerase chain reaction (PCR)
amplicon length (ssPAL) differences to define the fractional composition of
murine and human DNA, which was proportional to the fractional composition of
cells in a series of lung cancer PDX lines. We compared four methods of human
cancer cell isolation: fluorescence-activated cell sorting (FACS), an
immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based
immunomagnetic positive selection methods. We further analyzed DNA extracted from
the resulting enriched human cancer cells by targeted sequencing using a
clinically validated multi-gene panel. Stromal content varied widely among tumors
of similar histology, but appeared stable over multiple serial tumor passages of
an individual model. FACS and MCD were superior to either positive selection
approach, especially in cases of high stromal content, and consistently allowed
high quality human-specific genomic profiling. ssPAL is a dependable approach to
quantitation of murine stromal content, and MCD is a simple, efficient, and high
yield approach to human cancer cell isolation for genomic analysis of PDX tumors.
PMID- 27611666
TI - Treatment Options for Nonunion With Segmental Bone Defects: Systematic Review and
Quantitative Evidence Synthesis.
AB - OBJECTIVES: To determine which reconstruction treatment of long bones nonunion
with segmental bone defects (SBDs) is effective to restore bone length and union
with good function. DATA SOURCES: PubMed was used to identify published
literature on treatment of SBD caused by fracture nonunion regardless of
infection between January 1975 and December 2014. STUDY SELECTION: We included
retrospective cohort studies with a minimum sample size of 10 consecutive
patients with minimum follow-up of 18 months and available data on radiographic
and functional outcomes. DATA EXTRACTION: Literature review revealed 24
publications with a sample size of 504 patients (395 males, 109 females). Data on
bone union and functional outcome and complications were collected and analyzed
based on validated classification systems. DATA SYNTHESIS: Two outcome groups
were categorized for bone union and functional outcome, success, and failure. We
then performed heterogeneity test to examine the variability or differences in
the methods used by these studies and based on that we determined whether the
fixed effect or random effect method is appropriate in examining the summary or
pool estimate. Pool estimate was examined for bone union and functional outcome
in each surgical modality and in each anatomic location when data were available.
CONCLUSIONS: Treatment of SBD can be challenging. This quantitative evidence
synthesis shows that bone union was achieved by different procedures with
variable bone union and functional outcomes. LEVEL OF EVIDENCE: Therapeutic Level
IV. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 27611665
TI - Cell Division Cycle 6 Promotes Mitotic Slippage and Contributes to Drug
Resistance in Paclitaxel-Treated Cancer Cells.
AB - Paclitaxel (PTX) is an antimitotic drug that possesses potent anticancer
activity, but its therapeutic potential in the clinic has been hindered by drug
resistance. Here, we report a mechanism by which cancer cells can exit from the
PTX-induced mitotic arrest, i.e. mitotic slippage, and avoid subsequent death
resulting in drug resistance. In cells experiencing mitotic slippage, Cdc6
protein level was significantly upregulated, Cdk1 activity was inhibited, and
Cohesin/Rad21 was cleaved as a result. Cdc6 depletion by RNAi or Norcantharidin
inhibited PTX-induced Cdc6 up-regulation, maintained Cdk1 activity, and repressed
Cohesin/Rad21 cleavage. In all, this resulted in reduced mitotic slippage and
reversal of PTX resistance. Moreover, in synchronized cells, the role of Cdc6 in
mitotic exit under PTX pressure was also confirmed. This study indicates that
Cdc6 may promote mitotic slippage by inactivation of Cdk1. Targeting of Cdc6 may
serve as a promising strategy for enhancing the anticancer activity of PTX.
PMID- 27611667
TI - Higher Charlson Comorbidity Index Scores Are Associated With Increased Hospital
Length of Stay After Lower Extremity Orthopaedic Trauma.
AB - OBJECTIVES: The purpose of this study was to explore the relationship between
preoperative Charlson Comorbidity Index (CCI) and postoperative length of stay
(LOS) for lower extremity and hip/pelvis orthopaedic trauma patients. DESIGN:
Retrospective. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: A
total of 1561 patients treated for isolated lower extremity and pelvis fractures
between 2000 and 2012. INTERVENTIONS: Surgical intervention for fractures MAIN
OUTCOME MEASUREMENTS:: The main outcome metric was LOS. Negative binomial
regression analysis was used to examine the association between CCI and LOS while
controlling for significant confounders. RESULTS: One thousand five hundred sixty
one patients met the inclusion criteria, 1302 (83.4%) of which had lower
extremity injuries and 259 (16.6%) experienced hip/pelvis trauma. A total of 1001
(64.1%) patients presented with a CCI score of 1 and stayed an average of 7.9
days. Patients with a CCI of 3 experienced a mean LOS of 1.2 days longer than
patients presenting with a CCI of 1, whereas patients presenting with a CCI score
of 5 stayed an average of 4.6 days longer. After controlling for age, race,
American Society of Anesthesiologists score, sex, anesthesia type, and anesthesia
time, a higher preoperative CCI was found to be associated with longer LOS for
patients with lower extremity fractures (Incidence Rate Ratio: 1.04, P = 0.01).
No significant association was found between CCI and LOS for patients with
hip/pelvic fractures. CONCLUSIONS: This study demonstrated the potential utility
of the CCI as a predictor of hospital LOS for lower extremity patients; however,
the association may be small given the smaller Incidence Rate Ratio value.
Further studies are needed to clarify the predictive value of the CCI for
different types of orthopaedic injuries. LEVEL OF EVIDENCE: Prognostic Level III.
See Instructions for Authors for a complete.
PMID- 27611669
TI - Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa,
Constitutional Thinness and Healthy Obesity.
AB - INTRODUCTION: Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis
as demonstrated in rodents. Anorexia nervosa is characterized by restrained
eating behavior despite adaptive orexigenic regulation profile including high
ghrelin plasma levels. Constitutional thinness is a physiological condition of
resistance to weight gain with physiological anorexigenic profile including high
Peptide YY plasma level. Healthy obesity can be considered as a physiological
state of resistance to weight loss with opposite appetite regulating profile to
constitutional thinness including low Peptide YY plasma level. No studies in IL-7
are yet available in those populations. Therefore we evaluated circadian plasma
levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy
obese and control females. MATERIALS AND METHODS: 10 restrictive-type anorexia
nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive
anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7
healthy obese females, and 10 normal weight women controls were enrolled in this
cross-sectional study, performed in endocrinology unit and academic laboratory.
Twelve-point circadian profiles of plasma IL-7 levels were measured in each
subject. RESULTS: 24h mean IL-7 plasma levels (pg/ml, mean+/-SEM) were decreased
in restrictive-type anorexia nervosa (123.4+/-14.4, p<0.0037), bingeing/purging
anorexia nervosa (24.2+/-5.6, p<0.001), recovered restrictive anorexia nervosa
(64.2+/-16.1, p = 0.01) and healthy obese patients (51+/-3.2, p<0.001) compared
to controls (187.7+/-28.6). Bulimic patients (197.4+/-42.7) and constitutional
thinness patients (264.3+/-35.8) were similar to controls. CONCLUSIONS: Low IL-7
is part of the adaptive profile in restrictive-type anorexia nervosa, confirming
its difference with constitutional thinness. Healthy obesity, with low IL-7, is
once again in mirror image of constitutional thinness with normal high IL-7.
PMID- 27611670
TI - Phenotypic and Molecular Alterations in the Mammary Tissue of R-Spondin1 Knock
Out Mice during Pregnancy.
AB - R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic
functions in development and stem cell growth. Rspo1 knock-out mice are sex
reversed, but some remain sub-fertile, so they fail to nurse their pups. A lack
of Rspo1 expression in the mammary gland results in an absence of duct side
branching development and defective alveolar formation. The aim of this study was
to characterize the phenotypic and molecular alterations of mammary gland due to
Rspo1 knock-out. Using the transcriptional profiling of mammary tissues, we
identified misregulated genes in the mammary gland of Rspo1 knock-out mice during
pregnancy. A stronger expression of mesenchymal markers was observed, without
modifications to the structure of mammary epithelial tissue. Mammary epithelial
cell immunohistochemical analysis revealed a persistence of virgin markers, which
signify a delay in cell differentiation. Moreover, serial transplantation
experiments showed that Rspo1 is associated with a regenerative potential of
mammary epithelial cell control. Our finding also highlights the negatively
regulated expression of Rspo1's partners, Lgr4 and RNF43, in the mammary gland
during pregnancy. Moreover, we offer evidence that Tgf-beta signalling is
modified in the absence of Rspo1. Taken together, our results show an abrupt halt
or delay to mammary development during pregnancy due to the loss of a further
differentiated function.
PMID- 27611672
TI - Year's comments for 2015.
PMID- 27611671
TI - Implication of Terminal Residues at Protein-Protein and Protein-DNA Interfaces.
AB - Terminal residues of protein chains are charged and more flexible than other
residues since they are constrained only on one side. Do they play a particular
role in protein-protein and protein-DNA interfaces? To answer this question, we
considered large sets of non-redundant protein-protein and protein-DNA complexes
and analyzed the status of terminal residues and their involvement in interfaces.
In protein-protein complexes, we found that more than half of terminal residues
(62%) are either modified by attachment of a tag peptide (10%) or have missing
coordinates in the analyzed structures (52%). Terminal residues are almost
exclusively located at the surface of proteins (94%). Contrary to charged
residues, they are not over or under-represented in protein-protein interfaces,
but strongly prefer the peripheral region of interfaces when present at the
interface (83% of terminal residues). The almost exclusive location of terminal
residues at the surface of the proteins or in the rim regions of interfaces
explains that experimental methods relying on tail hybridization can be
successfully applied without disrupting the complexes under study. Concerning
conformational rearrangement in protein-protein complexes, despite their expected
flexibility, terminal residues adopt similar locations between the free and bound
forms of the docking benchmark. In protein-DNA complexes, N-terminal residues are
twice more frequent than C-terminal residues at interfaces. Both N-terminal and C
terminal residues are under-represented in interfaces, in contrast to positively
charged residues, which are strongly favored. When located in protein-DNA
interfaces, terminal residues prefer the periphery. N-terminal and C-terminal
residues thus have particular properties with regard to interfaces, which cannot
be reduced to their charged nature.
PMID- 27611673
TI - Chromosomes of Protists: The crucible of evolution.
AB - As early as 1925, the great protozoologist Edouard Chatton classified
microorganisms into two categories, the prokaryotic and the eukaryotic microbes,
based on light microscopical observation of their nuclear organization. Now, by
means of transmission electron microscopy, we know that prokaryotic microbes are
characterized by the absence of nuclear envelope surrounding the bacterial
chromosome, which is more or less condensed and whose chromatin is deprived of
histone proteins but presents specific basic proteins. Eukaryotic microbes, the
protists, have nuclei surrounded by a nuclear envelope and have chromosomes more
or less condensed, with chromatin-containing histone proteins organized into
nucleosomes. The extraordinary diversity of mitotic systems presented by the 36
phyla of protists (according to Margulis et al., Handbook of Protoctista, 1990)
is in contrast to the relative homogeneity of their chromosome structure and
chromatin components. Dinoflagellates are the exception to this pattern. The
phylum is composed of around 2000 species, and characterized by unique features
including their nucleus (dinokaryon), dinomitosis, chromosome organization and
chromatin composition. Although their DNA synthesis is typically eukaryotic,
dinoflagellates are the only eukaryotes in which the chromatin, organized into
quasi-permanently condensed chromosomes, is in some species devoid of histones
and nucleosomes. In these cases, their chromatin contains specific DNA-binding
basic proteins. The permanent compaction of their chromosomes throughout the cell
cycle raises the question of the modalities of their division and their
transcription. Successful in vitro reconstitution of nucleosomes using
dinoflagellate DNA and heterologous corn histones raises questions about
dinoflagellate evolution and phylogeny. [Int Microbiol 18(4):209-216 (2015)].
PMID- 27611674
TI - Archaeal and bacterial diversity in two hot springs from geothermal regions in
Bulgaria as demostrated by 16S rRNA and GH-57 genes.
AB - Archaeal and bacterial diversity in two Bulgarian hot springs, geographically
separated with different tectonic origin and different temperature of water was
investigated exploring two genes, 16S rRNA and GH-57. Archaeal diversity was
significantly higher in the hotter spring Levunovo (LV) (82 degrees C); on the
contrary, bacterial diversity was higher in the spring Vetren Dol (VD) (68
degrees C). The analyzed clones from LV library were referred to twenty eight
different sequence types belonging to five archaeal groups from Crenarchaeota and
Euryarchaeota. A domination of two groups was observed, Candidate Thaumarchaeota
and Methanosarcinales. The majority of the clones from VD were referred to HWCG
(Hot Water Crenarchaeotic Group). The formation of a group of thermophiles in the
order Methanosarcinales was suggested. Phylogenetic analysis revealed high
numbers of novel sequences, more than one third of archaeal and half of the
bacterial phylotypes displayed similarity lower than 97% with known ones. The
retrieved GH-57 gene sequences showed a complex phylogenic distribution. The main
part of the retrieved homologous GH-57 sequences affiliated with bacterial phyla
Bacteroidetes, Deltaproteobacteria, Candidate Saccharibacteria and affiliation of
almost half of the analyzed sequences is not fully resolved. GH-57 gene analysis
allows an increased resolution of the biodiversity assessment and in depth
analysis of specific taxonomic groups. [Int Microbiol 18(4):217-223 (2015)].
PMID- 27611675
TI - Chlamydia pneumoniae CPj0783 interaction with Huntingtin-protein14.
AB - Chlamydia pneumoniae is a Gram-negative, obligate intracellular pathogen that
causes community-acquired respiratory infections. After C. pneumoniae invades
host cells, it disturbs the vesicle transport system to escape host lysosomal or
autophagosomal degradation. By using a yeast mis-sorting assay, we found 10 C.
pneumoniae candidate genes involved in aberrant vesicular trafficking in host
cells. One of the candidate genes, CPj0783, was recognized by antibodies from C.
pneumoniae-infected patients. The expression of CPj0783 was detected at mid to
late-cycle time points and increased during the inclusion maturation. Two-hybrid
screening in yeast cells revealed that CPj0783 interacted with Huntingtin
interacting protein 14 (HIP14). The specific interaction between CPj0783 and
HIP14 could be demonstrated by an in vivo co-immunoprecipitation assay and an in
vitro GST pull-down assay. It was also demonstrated that HIP14 was localized in
the Golgi apparatus and colocalized with CPj0783. HIP14 has a palmitoyl
transferase activity that is involved in the palmitoylation-dependent vesicular
trafficking of several acylated proteins. These findings suggest that CPj0783
might cause abnormal vesicle-mediated transport by interacting with HIP14. [Int
Microbiol 18(4):225-233 (2015)].
PMID- 27611676
TI - A Kluyveromyces marxianus 2-deoxyglucose-resistant mutant with enhanced activity
of xylose utilization.
AB - Thermotolerant ethanologenic yeast Kluyveromyces marxianus is capable of
fermenting various sugars including xylose but glucose represses to hamper the
utilization of other sugars. To acquire glucose repression-defective strains, 33
isolates as 2-deoxyglucose (2-DOG)-resistant mutants were acquired from about 100
colonies grown on plates containing 2-DOG, which were derived from an efficient
strain DMKU 3-1042. According to the characteristics of sugar consumption
abilities and cell growth and ethanol accumulation along with cultivation time,
they were classified into three groups. The first group (3 isolates) utilized
glucose and xylose in similar patterns along with cultivation to those of the
parental strain, presumably due to reduction of the uptake of 2-DOG or
enhancement of its export. The second group (29 isolates) showed greatly delayed
utilization of glucose, presumably by reduction of the uptake or initial
catabolism of glucose. The last group, only one isolate, showed enhanced
utilization ability of xylose in the presence of glucose. Further analysis
revealed that the isolate had a single nucleotide mutation to cause amino acid
substitution (G270S) in RAG5 encoding hexokinase and exhibited very low activity
of the enzyme. The possible mechanism of defectiveness of glucose repression in
the mutant is discussed in this paper. [Int Microbiol 18(4):235-244 (2015)].
PMID- 27611677
TI - Interaction and cooperative effort among scientific societies. Twelve years of
COSCE.
AB - The evolution of knowledge and technology in recent decades has brought profound
changes in science policy, not only in the countries but also in the
supranational organizations. It has been necessary, therefore, to adapt the
scientific institutions to new models in order to achieve a greater and better
communication between them and the political counterparts responsible for
defining the general framework of relations between science and society. The
Federationon of Scientific Societies of Spain (COSCE, Confederacion de Sociedades
Cientificas de Espana) was founded in October 2003 to respond to the urgent need
to interact with the political institutions and foster a better orientation in
the process of making decisions about the science policy. Currently COSCE
consists of over 70 Spanish scientific societies and more than 40,000 scientists.
During its twelve years of active life, COSCE has developed an intense work of
awareness of the real situation of science in Spain by launching several
initiatives (some of which have joined other organizations) or by joining
initiatives proposed from other groups related to science both at the Spanish
level and at the European and non-European scenarios. [Int Microbiol 18(4): 245
251 (2015)].
PMID- 27611678
TI - Hypercompetition in biomedical research evaluation and its impact on young
scientist careers.
AB - Recent years have seen tremendous changes in the modes of publication and
dissemination of biomedical information, with the introduction of countless new
publishers and publishing models, as well as alternative modes of research
evaluation. In parallel, we are witnessing an unsustainable explosion in the
amount of information generated by each individual scientist, at the same time as
many countries' shrinking research budgets are greatly increasing the competition
for research funding. In such a hypercompetitive environment, how does one
measure excellence? This contribution will provide an overview of some of the
ongoing changes in authorship practices in the biomedical sciences, and also the
consequences of hypercompetition to the careers of young scientists, from the
perspective of a tenured young faculty member in the biomedical sciences. It will
also provide some suggestions as to alternate dissemination and evaluation
practices that could reverse current trends. [Int Microbiol 18(4):253-261
(2015)].
PMID- 27611679
TI - Identification of Gastric Cancer Biomarkers Using 1H Nuclear Magnetic Resonance
Spectrometry.
AB - Existing gastric cancer diagnosing methods were invasive, hence, a reliable non
invasive gastric cancer diagnosing method is needed. As a starting point, we used
1H NMR for identifying gastric cancer biomarkers using a panel of gastric cancer
spheroids and normal gastric spheroids. We were able to identify 8 chemical shift
biomarkers for gastric cancer spheroids. Our data suggests that the cancerous and
non-cancerous spheroids significantly differ in the lipid composition and energy
metabolism. These results encourage the translation of these biomarkers into in
vivo gastric cancer detection methodology using MRI-MS.
PMID- 27611680
TI - Detecting Visual Function Abnormality with a Contrast-Dependent Visual Test in
Patients with Type 2 Diabetes.
AB - In addition to diabetic retinopathy, diabetes also causes early retinal
neurodegeneration and other eye problems, which cause various types of visual
deficits. This study used a computer-based visual test (Macular Multi-Function
Assessment (MMFA)) to assess contrast-dependent macular visual function in
patients with type 2 diabetes to collect more visual information than possible
with only the visual acuity test. Because the MMFA is a newly developed test,
this study first compared the agreement and discriminative ability of the MMFA
and the Early Treatment Diabetic Retinopathy Study (ETDRS) contrast acuity
charts. Then symbol discrimination performances of diabetic patients and controls
were evaluated at 4 contrast levels using the MMFA. Seventy-seven patients and 45
controls participated. The agreement between MMFA and ETDRS scores was examined
by fitting three-level linear mixed-effect models to estimate the intraclass
correlation coefficients (ICCs). The estimated areas under the receiver operating
characteristic (ROC) curve were used to compare the discriminative ability of
diseased versus non-diseased participants between the two tests. The MMFA scores
of patients and controls were compared with multiple linear regression analysis
after adjusting the effects of age, sex, hypertension and cataract. Results
showed that the scores of the MMFA and ETDRS tests displayed high levels of
agreement and acceptable and similar discriminative ability. The MMFA performance
was correlated with the severity of diabetic retinopathy. Most of the MMFA scores
differed significantly between the diabetic patients and controls. In the low
contrast condition, the MMFA scores were significantly lower for 006Eon-DR
patients than for controls. The potential utility of the MMFA as an easy
screening tool for contrast-dependent visual function and for detecting early
functional visual change in patients with type 2 diabetes is discussed.
PMID- 27611682
TI - Whole Genome Mapping with Feature Sets from High-Throughput Sequencing Data.
AB - A good physical map is essential to guide sequence assembly in de novo whole
genome sequencing, especially when sequences are produced by high-throughput
sequencing such as next-generation-sequencing (NGS) technology. We here present a
novel method, Feature sets-based Genome Mapping (FGM). With FGM, physical map and
draft whole genome sequences can be generated, anchored and integrated using the
same data set of NGS sequences, independent of restriction digestion. Method
model was created and parameters were inspected by simulations using the
Arabidopsis genome sequence. In the simulations, when ~4.8X genome BAC library
including 4,096 clones was used to sequence the whole genome, ~90% of clones were
successfully connected to physical contigs, and 91.58% of genome sequences were
mapped and connected to chromosomes. This method was experimentally verified
using the existing physical map and genome sequence of rice. Of 4,064 clones
covering 115 Mb sequence selected from ~3 tiles of 3 chromosomes of a rice draft
physical map, 3,364 clones were reconstructed into physical contigs and 98 Mb
sequences were integrated into the 3 chromosomes. The physical map-integrated
draft genome sequences can provide permanent frameworks for eventually obtaining
high-quality reference sequences by targeted sequencing, gap filling and
combining other sequences.
PMID- 27611683
TI - A Spatio-Temporally Explicit Random Encounter Model for Large-Scale Population
Surveys.
AB - Random encounter models can be used to estimate population abundance from
indirect data collected by non-invasive sampling methods, such as track counts or
camera-trap data. The classical Formozov-Malyshev-Pereleshin (FMP) estimator
converts track counts into an estimate of mean population density, assuming that
data on the daily movement distances of the animals are available. We utilize
generalized linear models with spatio-temporal error structures to extend the FMP
estimator into a flexible Bayesian modelling approach that estimates not only
total population size, but also spatio-temporal variation in population density.
We also introduce a weighting scheme to estimate density on habitats that are not
covered by survey transects, assuming that movement data on a subset of
individuals is available. We test the performance of spatio-temporal and temporal
approaches by a simulation study mimicking the Finnish winter track count survey.
The results illustrate how the spatio-temporal modelling approach is able to
borrow information from observations made on neighboring locations and times when
estimating population density, and that spatio-temporal and temporal smoothing
models can provide improved estimates of total population size compared to the
FMP method.
PMID- 27611681
TI - Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies
and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and
Compensated Patients Examined Antemortem Irrespective of the HAART Era.
AB - OBJECTIVE: AIDS-related mortality has changed dramatically with the onset of
highly active antiretroviral therapy (HAART), which has even allowed compensated
HIV-infected patients to withdraw from secondary therapy directed against
opportunistic pathogens. However, in recently autopsied HIV-infected patients, we
observed that associations with a broad spectrum of pathogens remain, although
detailed analyses are lacking. Therefore, we focused on the possible frequency
and spectrum shifts in pathogens associated with autopsied HIV-infected patients.
DESIGN: We hypothesized that the pathogens frequency and spectrum changes found
in HIV-infected patients examined postmortem did not recapitulate the changes
found previously in HIV-infected patients examined antemortem in both the pre-
and post-HAART eras. Because this is the first comprehensive study originating
from Central and Eastern Europe, we also compared our data with those obtained in
the West and Southwest Europe, USA and Latin America. METHODS: We performed
autopsies on 124 HIV-infected patients who died from AIDS or other co-morbidities
in the Czech Republic between 1985 and 2014. The pathological findings were
retrieved from the full postmortem examinations and autopsy records. RESULTS: We
collected a total of 502 host-pathogen records covering 82 pathogen species, a
spectrum that did not change according to patients' therapy or since the onset of
the epidemics, which can probably be explained by the fact that even recently
deceased patients were usually decompensated (in 95% of the cases, the last
available CD4+ cell count was falling below 200 cells*MUl-1) regardless of the
treatment they received. The newly identified pathogen taxa in HIV-infected
patients included Acinetobacter calcoaceticus, Aerococcus viridans and
Escherichia hermannii. We observed a very limited overlap in both the spectra and
frequencies of the pathogen species found postmortem in HIV-infected patients in
Europe, the USA and Latin America. CONCLUSIONS: The shifts documented previously
in compensated HIV-infected patients examined antemortem in the post-HAART era
are not recapitulated in mostly decompensated HIV-infected patients examined
postmortem.
PMID- 27611685
TI - Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate
Nucleus of the Hypothalamus.
AB - The cholinoceptive system in the hypothalamus, in particular in the arcuate
nucleus (ARC), plays a role in regulating food intake. Neurons in the ARC contain
multiple neuropeptides, amines, and neurotransmitters. To study molecular and
neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and
single-cell whole transcriptome amplification methods to analyze expression
patterns of our hand-picked 60 genes in individual neurons in the ARC.
Immunohistochemical and single-cell qRT-PCR analyses show choline
acetyltransferase (ChAT)-expressing neurons in the ARC. Gene expression patterns
are remarkably distinct in each individual cholinergic neuron. Two-thirds of
cholinergic neurons express tyrosine hydroxylase (Th) mRNA. A large subset of
these Th-positive cholinergic neurons is GABAergic as they express the GABA
synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter
transcripts. Some cholinergic neurons also express the vesicular glutamate
transporter transcript gene. POMC and POMC-processing enzyme transcripts are
found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene
expression patterns in individual cholinergic cells appear to be highly regulated
in a cell-specific manner. In fact, membrane receptor transcripts are clustered
with their respective intracellular signaling and downstream targets. This novel
population of cholinergic neurons may be part of the neural circuitries that
detect homeostatic need for food and control the drive to eat.
PMID- 27611684
TI - mSWI/SNF (BAF) Complexes Are Indispensable for the Neurogenesis and Development
of Embryonic Olfactory Epithelium.
AB - Neurogenesis is a key developmental event through which neurons are generated
from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes
have been reported to play essential roles in the neurogenesis of the central
nervous system. However, whether BAF complexes are required for neuron generation
in the olfactory system is unknown. Here, we identified onscBAF and ornBAF
complexes, which are specifically present in olfactory neural stem cells (oNSCs)
and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155
subunit is highly expressed in both oNSCs and ORNs, whereas high expression of
BAF170 subunit is observed only in ORNs. We report that conditional deletion of
BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired
proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs
in the developing olfactory epithelium (OE), while the high expression of BAF170
is important for maturation of ORNs. Interestingly, in the absence of BAF
complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not
specified. Mechanistically, BAF complex is required for normal activation of Pax6
dependent transcriptional activity in stem cells/progenitors of the OE. Our
findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE
neurogenesis and development.
PMID- 27611686
TI - Reputation-Based Investment Helps to Optimize Group Behaviors in Spatial Lattice
Networks.
AB - Encouraging cooperation among selfish individuals is crucial in many real-world
systems, where individuals' collective behaviors can be analyzed using
evolutionary public goods game. Along this line, extensive studies have shown
that reputation is an effective mechanism to investigate the evolution of
cooperation. In most existing studies, participating individuals in a public
goods game are assumed to contribute unconditionally into the public pool, or
they can choose partners based on a common reputation standard (e.g., preferences
or characters). However, to assign one reputation standard for all individuals is
impractical in many real-world deployment. In this paper, we introduce a
reputation tolerance mechanism that allows an individual to select its potential
partners and decide whether or not to contribute an investment to the public pool
based on its tolerance to other individuals' reputation. Specifically, an
individual takes part in a public goods game only if the number of participants
with higher reputation exceeds the value of its tolerance. Moreover, in this
paper, an individual's reputation can increase or decrease in a bounded interval
based on its historical behaviors. We explore the principle that how the
reputation tolerance and conditional investment mechanisms can affect the
evolution of cooperation in spatial lattice networks. Our simulation results
demonstrate that a larger tolerance value can achieve an environment that promote
the cooperation of participants.
PMID- 27611687
TI - The Impact of Reconstruction Methods, Phylogenetic Uncertainty and Branch Lengths
on Inference of Chromosome Number Evolution in American Daisies (Melampodium,
Asteraceae).
AB - Chromosome number change (polyploidy and dysploidy) plays an important role in
plant diversification and speciation. Investigating chromosome number evolution
commonly entails ancestral state reconstruction performed within a phylogenetic
framework, which is, however, prone to uncertainty, whose effects on evolutionary
inferences are insufficiently understood. Using the chromosomally diverse plant
genus Melampodium (Asteraceae) as model group, we assess the impact of
reconstruction method (maximum parsimony, maximum likelihood, Bayesian methods),
branch length model (phylograms versus chronograms) and phylogenetic uncertainty
(topological and branch length uncertainty) on the inference of chromosome number
evolution. We also address the suitability of the maximum clade credibility (MCC)
tree as single representative topology for chromosome number reconstruction. Each
of the listed factors causes considerable incongruence among chromosome number
reconstructions. Discrepancies between inferences on the MCC tree from those made
by integrating over a set of trees are moderate for ancestral chromosome numbers,
but severe for the difference of chromosome gains and losses, a measure of the
directionality of dysploidy. Therefore, reliance on single trees, such as the MCC
tree, is strongly discouraged and model averaging, taking both phylogenetic and
model uncertainty into account, is recommended. For studying chromosome number
evolution, dedicated models implemented in the program ChromEvol and ordered
maximum parsimony may be most appropriate. Chromosome number evolution in
Melampodium follows a pattern of bidirectional dysploidy (starting from x = 11 to
x = 9 and x = 14, respectively) with no prevailing direction.
PMID- 27611688
TI - Epidemic History of Hepatitis C Virus among Patients with Inherited Bleeding
Disorders in Iran.
AB - The high rate of hepatitis C virus (HCV) infection among transfusion related risk
groups such as patients with inherited bleeding disorders highlighting the
investigation on prevalent subtypes and their epidemic history among this group.
In this study, 166 new HCV NS5B sequences isolated from patients with inherited
bleeding disorders together with 29 sequences related to hemophiliacs obtained
from a previous study on diversity of HCV in Iran were analyzed. The most
prevalent subtype was 1a (65%), followed by 3a (18.7%),1b (14.5%),4(1.2%) and 2k
(0.6%). Subtypes 1a and 3a showed exponential expansion during the 20th century.
Whereas expansion of 3a started around 20 years earlier than 1a among the study
patients, the epidemic growth of 1a revealed a delay of about 10 years compared
with that found for this subtype in developed countries. Our results supported
the view that the spread of 3a reached the plateau 10 years prior to the
screening of blood donors for HCV. Rather, 1a reached the plateau when screening
program was implemented. The differences observed in the epidemic behavior of HCV
1a and 3a may be associated with different transmission routes of two subtypes.
Indeed, expansion of 1a was more commonly linked to blood transfusion, while 3a
was more strongly associated to drug use and specially IDU after 1960. Our
findings also showed HCV transmission through blood products has effectively been
controlled from late 1990s. In conclusion, the implementation of strategies such
as standard surveillance programs and subsiding antiviral treatments seems to be
essential to both prevent new HCV infections and to decline the current and
future HCV disease among Iranian patients with inherited bleeding disorders.
PMID- 27611689
TI - Physical Activity and Health Perception in Aging: Do Body Mass and Satisfaction
Matter? A Three-Path Mediated Link.
AB - Although ageing people could benefit from healthy diet and physical activity to
maintain health and quality of life, further understandings of the diet- and
physical activity-related mechanisms that may cause changes in health and quality
of life perception are necessary. The purpose of the study was to investigate the
effect of eating attitudes, body mass and image satisfaction, and exercise
dependence in the relationship between physical activity and health and quality
of life perception in older individuals. Hundred and seventy-nine late middle
aged, (55-64 yrs), young-old (65-74 yrs), and old (75-84 yrs) senior athletes (n
= 56), physically active (n = 58) or sedentary adults (n = 65) were submitted to
anthropometric evaluations (body mass, height) and self-reported questionnaires:
Body Image Dimensional Assessment, Exercise Dependence Scale, Eating Attitude
Test, and Short Form Health Survey (Physical Component Summary [PCS] and Mental
Component Summary [MCS] of and health and quality of life perception). Senior
athletes, physically active, and sedentary participants subgroups differed
(P<0.05) from each other in body mass index (BMI) and several components of body
image and exercise dependence. Senior athletes showed, compared to their
sedentary counterparts, further differences (P<0.05) in eating attitudes and in
both PCS and MCS. Mediation analysis showed that the relationship between
physical activity habit and MCS, but not PCS, was indirectly explained by a
serial mediation chain composed of objective BMI and subjective body image
(dis)satisfaction. Findings confirm the relevant role of physically active life
habits for older individuals to perceive good physical and mental health. The
novelty of the three-path mediated link between physical activity level and
mental health perception suggests that the beneficial effect of a physically
active lifestyle on weight control can positively impinge on the cognitive
emotional dimension of mental health by ensuring the maintenance, also at older
age, of a satisfactory body image.
PMID- 27611690
TI - In Silico and Biochemical Characterization of Lysozyme-Like Proteins in the Rat.
AB - BACKGROUND: Spermatogenesis and sperm maturation in the male reproductive tract
is dictated by a variety of proteins secreted in the testis and epididymis.
Though the proteome of these tissues is known, the functional role of many of
these proteins remains uncharacterized. In this study, we characterize the rat
Lysozyme-like (Lyzl) genes and proteins. METHODS: In silico tools were used to
predict the primary, secondary and tertiary structures. Reverse transcription
PCR, immunofluorescence and immunoblotting were used to determine the expression
pattern. Lysozyme like enzyme activity was assessed by standard assays. RESULTS:
Six rat Lyzl genes namely Lyzl1, Lyzl3, Lyzl4, Lyzl5, Lyzl6 and Lyzl7 were found
to be highly conserved among the vertebrates with higher homology to mouse
counterparts than with human counterparts. All the LYZL proteins contained the
characteristic 4 disulfide bridges similar to c-type lysozyme. Only LYZL 1 and 6,
conserved the active site amino acids of the lysozyme. Molecular modeling studies
indicated that LYZL proteins exhibit strikingly similar three-dimensional
structures among themselves. The secondary structure analysis of the recombinant
LYZL proteins indicated the presence of alpha-helix, beta-sheet and random coil
with alpha-helix being the majority. Docking studies indicated the peptidoglycan
binding nature of LYZL proteins. All the rat Lyzl mRNA transcripts (Lyzl1, Lyzl3,
Lyzl4, Lyzl5, Lyzl6 and Lyzl7) are predominantly expressed in testes though some
of them are expressed in tissues other than reproductive tract. Their expression
was androgen independent. The rat LYZL proteins are localized in the germinal
epithelium and on the spermatozoa. Recombinant LYZL1 and 6 possessed muramidase,
isopeptidase and antibacterial activities. The mechanism of antibacterial action
of LYZL1 and LYZL6 involved bacterial membrane damage and leakage of cellular
contents. Only LYZL1 and 6 possess peptidoglycan binding ability, whereas LYZL3,
LYZL4 and LYZL5 possess hyaluronan binding ability suggesting a possible
functional divergence of these proteins. LYZL3, LYZL4 and LYZL7 possessed free
radical scavenging property, suggesting that they may act as antioxidants.
CONCLUSION: The divergent properties of LYZL proteins indicate that they may have
a role in sperm function, innate immunity and other physiological process as
well.
PMID- 27611692
TI - The Effectiveness of Cognitive Bias Modification Interventions for Substance
Addictions: A Meta-Analysis.
AB - BACKGROUND AND AIMS: Cognitive bias modification (CBM) interventions, presumably
targeting automatic processes, are considered particularly promising for
addictions. We conducted a meta-analysis examining randomized controlled trials
(RCTs) of CBM for substance addiction outcomes. METHODS: Studies were identified
through systematic searches in bibliographical databases. We included RCTs of CBM
interventions, alone or in combination with other treatments, for any type of
addiction. We examined trial risk of bias, publication bias and possible
moderators. Effects sizes were computed for post-test and follow-up, using a
random-effects model. We grouped outcome measures and reported results for
addiction (all related measures), craving and cognitive bias. RESULTS: We
identified 25 trials, 18 for alcohol problems, and 7 for smoking. At post-test,
there was no significant effect of CBM for addiction, g = 0.08 (95% CI -0.02 to
0.18) or craving, g = 0.05 (95% CI -0.06 to 0.16), but there was a significant,
moderate effect on cognitive bias, g = 0.60 (95% CI 0.39 to 0.79). Results were
similar for alcohol and smoking outcomes taken separately. Follow-up addiction
outcomes were reported in 7 trials, resulting in a small but significant effect
of CBM, g = 0.18 (95% CI 0.03 to 0.32). Results for addiction and craving did not
differ by substance type, sample type, delivery setting, bias targeted or number
of sessions. Risk of bias was high or uncertain in most trials, for most criteria
considered. Meta-regression analyses revealed significant inverse relationships
between risk of bias and effect sizes for addiction outcomes and craving. The
relationship between cognitive bias and respectively addiction ESs was not
significant. There was consistent evidence of publication bias in the form of
funnel plot asymmetry. CONCLUSIONS: Our results cast serious doubts on the
clinical utility of CBM interventions for addiction problems, but sounder
methodological trials are necessary before this issue can be settled. We found no
indication that positive effects on biases translate into effects on addiction
outcomes.
PMID- 27611691
TI - Preclinical Metabolism, Pharmacokinetics and In Vivo Analysis of New Blood-Brain
Barrier Penetrant Fingolimod Analogues: FTY720-C2 and FTY720-Mitoxy.
AB - Parkinson's disease (PD) is a neurodegenerative aging disorder in which
postmortem PD brain exhibits neuroinflammation, as well as synucleinopathy
associated protein phosphatase 2A (PP2A) enzymatic activity loss. Based on our
translational research, we began evaluating the PD-repurposing-potential of an
anti-inflammatory, neuroprotective, and PP2A stimulatory oral drug that is FDA
approved for multiple sclerosis, FTY720 (fingolimod, Gilenya(r)). We also
designed two new FTY720 analogues, FTY720-C2 and FTY720-Mitoxy, with
modifications that affect drug potency and mitochondrial localization,
respectively. Herein, we describe the metabolic stability and metabolic profiling
of FTY720-C2 and FTY720-Mitoxy in liver microsomes and hepatocytes. Using mouse,
rat, dog, monkey, and human liver microsomes the intrinsic clearance of FTY720-C2
was 22.5, 79.5, 6.0, 20.2 and 18.3 MUL/min/mg; and for FTY720-Mitoxy was 1.8,
7.8, 1.4, 135.0 and 17.5 MUL/min/mg, respectively. In hepatocytes, both FTY720-C2
and FTY720-Mitoxy were metabolized from the octyl side chain, generating a series
of carboxylic acids similar to the parent FTY720, but without phosphorylated
metabolites. To assess absorption and distribution, we gave equivalent single
intravenous (IV) or oral doses of FTY720-C2 or FTY720-Mitoxy to C57BL/6 mice,
with two mice per time point evaluated. After IV delivery, both FTY720-C2 and
FTY720-Mitoxy were rapidly detected in plasma and brain; and reached peak
concentrations at the first sampling time points. After oral dosing, FTY720-C2
was present in plasma and brain, although FTY720-Mitoxy was not orally
bioavailable. Brain-to-plasma ratio of both compounds increased time-dependently,
suggesting a preferential partitioning to the brain. PP2A activity in mouse
adrenal gland increased ~2-fold after FTY720-C2 or FTY720-Mitoxy, as compared to
untreated controls. In summary, FTY720-C2 and FTY720-Mitoxy both (i) crossed the
blood-brain-barrier; (ii) produced metabolites similar to FTY720, except without
phosphorylated species that cause S1P1-mediated-immunosuppression; and (iii)
stimulated in vivo PP2A activity, all of which encourage additional preclinical
assessment.
PMID- 27611694
TI - Cascading effects of defaunation on the coexistence of two specialized insect
seed predators.
AB - : Identification of the mechanisms enabling stable coexistence of species with
similar resource requirements is a central challenge in ecology. Such coexistence
can be facilitated by species at higher trophic levels through complex multi
trophic interactions, a mechanism that could be compromised by ongoing
defaunation. We investigated cascading effects of defaunation on Pachymerus cardo
and Speciomerus giganteus, the specialized insect seed predators of the
Neotropical palm Attalea butyracea, testing the hypothesis that vertebrate
frugivores and granivores facilitate their coexistence. Laboratory experiments
showed that the two seed parasitoid species differed strongly in their
reproductive ecology. Pachymerus produced many small eggs that it deposited
exclusively on the fruit exocarp (exterior). Speciomerus produced few large eggs
that it deposited exclusively on the endocarp, which is normally exposed only
after a vertebrate handles the fruit. When eggs of the two species were deposited
on the same fruit, Pachymerus triumphed only when it had a long head start, and
the loser always succumbed to intraguild predation. We collected field data on
the fates of 6569 Attalea seeds across sites in central Panama with contrasting
degrees of defaunation and wide variation in the abundance of vertebrate
frugivores and granivores. Speciomerus dominated where vertebrate communities
were intact, whereas Pachymerus dominated in defaunated sites. Variation in the
relative abundance of Speciomerus across all 84 sampling sites was strongly
positively related to the proportion of seeds attacked by rodents, an indicator
of local vertebrate abundance. SYNTHESIS: We show that two species of insect seed
predators relying on the same host plant species are niche differentiated in
their reproductive strategies such that one species has the advantage when fruits
are handled promptly by vertebrates and the other when they are not. Defaunation
disrupts this mediating influence of vertebrates and strongly favours one species
at the expense of the other, providing a case study of the cascading effects of
defaunation and its potential to disrupt coexistence of non-target species,
including the hyperdiverse phytophagous insects of tropical forests.
PMID- 27611693
TI - A Taz1- and Microtubule-Dependent Regulatory Relationship between Telomere and
Centromere Positions in Bouquet Formation Secures Proper Meiotic Divisions.
AB - During meiotic prophase, telomeres cluster, forming the bouquet chromosome
arrangement, and facilitate homologous chromosome pairing. In fission yeast,
bouquet formation requires switching of telomere and centromere positions.
Centromeres are located at the spindle pole body (SPB) during mitotic interphase,
and upon entering meiosis, telomeres cluster at the SPB, followed by centromere
detachment from the SPB. Telomere clustering depends on the formation of the
microtubule-organizing center at telomeres by the linker of nucleoskeleton and
cytoskeleton complex (LINC), while centromere detachment depends on disassembly
of kinetochores, which induces meiotic centromere formation. However, how the
switching of telomere and centromere positions occurs during bouquet formation is
not fully understood. Here, we show that, when impaired telomere interaction with
the LINC or microtubule disruption inhibited telomere clustering, kinetochore
disassembly-dependent centromere detachment and accompanying meiotic centromere
formation were also inhibited. Efficient centromere detachment required telomere
clustering-dependent SPB recruitment of a conserved telomere component, Taz1, and
microtubules. Furthermore, when artificial SPB recruitment of Taz1 induced
centromere detachment in telomere clustering-defective cells, spindle formation
was impaired. Thus, detachment of centromeres from the SPB without telomere
clustering causes spindle impairment. These findings establish novel regulatory
mechanisms, which prevent concurrent detachment of telomeres and centromeres from
the SPB during bouquet formation and secure proper meiotic divisions.
PMID- 27611695
TI - A review of superior vena cava flow measurement in the neonate by functional
echocardiography.
AB - : Neonatologists have begun using superior vena cava flow as assessed by
functional echocardiography to facilitate real-time decision-making on
cardiovascular care. This review aims to describe the basis of the technique,
summarise the evidence for its use and compare the technique to existing
clinical, biochemical and radiological techniques for assessing neonatal
circulatory status. CONCLUSION: Although echocardiographic measurements of
superior vena cava flow, like other measures of perfusion, are not perfect, their
noninvasive nature and ability to facilitate real-time decision-making means that
at present, they remain the best available methodology of monitoring central
perfusion in the neonatal population.
PMID- 27611698
TI - Barcodes to Biomes / Codes barres pour biomes.
PMID- 27611697
TI - A quantitative protocol for DNA metabarcoding of springtails (Collembola).
AB - We developed a novel protocol with superior quantitative analysis results for DNA
metabarcoding of Collembola, a major soil microarthropod order. Degenerate PCR
primers were designed for conserved regions in the mitochondrial cytochrome c
oxidase subunit I (mtCOI) and 16S ribosomal RNA (mt16S) genes based on published
collembolan mitogenomes. The best primer pair was selected based on its ability
to amplify each gene, irrespective of the species. DNA was extracted from 10
natural communities sampled in a temperate forest (with typically 25-30
collembolan species per 10 soil samples) and 10 mock communities (with seven
cultured collembolan species). The two gene regions were then amplified using the
selected primers, ligated with adapters for 454 technology, and sequenced.
Examination of the natural community samples showed that 32 and 36 operational
taxonomic units (defined at a 90% sequence similarity threshold) were recovered
from the mtCOI and mt16S data, respectively, which were comparable to the results
of the microscopic identification of 25 morphospecies. Further, sequence
abundances for each collembolan species from the mtCOI and mt16S data of the mock
communities, after normalization by using a species as the internal control,
showed good correlation with the number of individuals in the samples (R = 0.91
0.99), although relative species abundances within a mock community sample
estimated from sequences were skewed from community composition in terms of the
number of individuals or biomass of the species. Thus, this protocol enables the
comparison of collembolan communities in a quantitative manner by metabarcoding.
PMID- 27611696
TI - Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of
Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress.
AB - Thermal ablative therapies are important treatment options in the
multidisciplinary care of patients with hepatocellular carcinoma (HCC), but
lesions larger than 2-3 cm are plagued with high local recurrence rates and
overall survival of these patients remains poor. Currently no adjuvant therapies
exist to prevent local HCC recurrence in patients undergoing thermal ablation.
The molecular mechanisms mediating HCC resistance to thermal ablation induced
heat stress and local recurrence remain unclear. Here we demonstrate that the HCC
cells with a poor prognostic hepatic stem cell subtype (Subtype HS) are more
resistant to heat stress than HCC cells with a better prognostic hepatocyte
subtype (Subtype HC). Moreover, sublethal heat stress rapidly induces
phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dependent
protein kinase B (AKT) survival signaling in HCC cells in vitro and at the tumor
ablation margin in vivo. Conversely, inhibition of PI3K/mTOR complex 2 (mTORC2)
dependent AKT phosphorylation or direct inhibition of AKT function both enhance
HCC cell killing and decrease HCC cell survival to sublethal heat stress in both
poor and better prognostic HCC subtypes while mTOR complex 1 (mTORC1)-inhibition
has no impact. Finally, we showed that AKT isoforms 1, 2 and 3 are differentially
upregulated in primary human HCCs and that overexpression of AKT correlates with
worse tumor biology and pathologic features (AKT3) and prognosis (AKT1). Together
these findings define a novel molecular mechanism whereby heat stress induces
PI3K/mTORC2-dependent AKT survival signaling in HCC cells and provide a
mechanistic rationale for adjuvant AKT inhibition in combination with thermal
ablation as a strategy to enhance HCC cell killing and prevent local recurrence,
particularly at the ablation margin.
PMID- 27611699
TI - From Barcodes to Biomes: Special Issues from the 6th International Barcode of
Life Conference.
PMID- 27611700
TI - On the Neuroendocrinopathy of Critical Illness. Perspectives for Feeding and
Novel Treatments.
AB - Typical for critical illnesses are substantial alterations within the
hypothalamic-anterior pituitary-peripheral hormonal axes that are proportionate
to the risk of poor outcome. These neuroendocrine responses to critical illness
follow a biphasic pattern. The acute phase (first hours to days) is characterized
by an increased release of anterior pituitary hormones, whereas altered target
organ sensitivity and hormone metabolism result in low levels of the anabolic
peripheral effector hormones and contribute to the substantially elevated levels
of the catabolic hormone cortisol. The prolonged phase of critical illness is
hallmarked by a uniform suppression of the neuroendocrine axes, predominantly of
central/hypothalamic origin, which contributes to the low (or insufficiently high
in the case of cortisol) circulating levels of the target-organ hormones. Several
of the acute-phase adaptations to critical illness are due to or accentuated by
the concomitant fasting. Accepting the lack of macronutrients as well as the
neuroendocrine responses to such fasting in the acute phase of critical illness
has shown to beneficially affect outcome. In contrast, the neuroendocrine
alterations that occur in the chronic phase of illness while patients are fully
fed contribute to bone and skeletal muscle wasting and impose risk of
adrenocortical atrophy. The combined administration of those hypothalamic
releasing factors, which have been identified as suppressed or deficient during
prolonged critical illness, may be a promising strategy to enhance recovery. The
potential impact of treatment with such hypothalamic releasing factors on
recovery from critical illness as well as on long-term rehabilitation should be
investigated in future randomized controlled clinical trials.
PMID- 27611701
TI - Serum fibroblast growth factor 21 is a superior biomarker to other adipokines in
predicting incident diabetes.
AB - OBJECTIVE: Fibroblast growth factor 21 (FGF21) improves glucose and lipid
metabolism, but high circulating levels are found in type 2 diabetes, suggesting
FGF21 resistance. Serum FGF21 predicts incident diabetes, but its performance
compared to established and emerging predictors is not known. We aimed to study
the performance of FGF21 in diabetes prediction, relative to other adipokines and
established risk factors including 2-h plasma glucose (2hG) during the oral
glucose tolerance test (OGTT). DESIGN/PARTICIPANTS/MEASUREMENTS: We studied 1380
nondiabetic subjects from the Hong Kong Cardiovascular Risk Factor Prevalence
Study using the second visit (2000-2004) as baseline when serum levels of FGF21
and other adipokines were measured. Glycaemic status was assessed by OGTT.
Incident diabetes was defined as fasting glucose level (FG) >= 7 mmol/l or 2hG >=
11.1 mmol/l or use of antidiabetic agents, at subsequent visits. RESULTS: A total
of 123 participants developed diabetes over 9.0 years (median). On multivariable
logistic regression analysis, FGF21 (P = 0.003), adipocyte fatty acid-binding
protein (P = 0.003) and adiponectin (P = 0.035) were independent predictors of
incident diabetes. FGF21 had the best change in log likelihood when added to a
diabetes prediction model (DP) based on age, family history, smoking,
hypertension, BMI, dyslipidaemia and FG. It also improved the area under ROC
curve (AUROC) of diabetes prediction (DP) from 0.797 to 0.819 (P = 0.0072),
rendering its performance comparable to the 'DP + 2hG' model (AUROC=0.838, P =
0.19). CONCLUSIONS: As a biomarker for diabetes prediction, serum FGF21 appeared
to be superior to other adipokines and, on its own, could be considered as an
alternative to the OGTT.
PMID- 27611703
TI - Blood group A mothers are more likely to develop anemia during antenatal
intravenous immunoglobulin treatment of fetal and neonatal alloimmune
thrombocytopenia.
AB - BACKGROUND: Incompatibility between parental platelet (PLT) antigens may lead to
sensitization of mother and development of fetal and neonatal alloimmune
thrombocytopenia (FNAIT) resulting in fetal thrombocytopenia. Intravenous
immunoglobulin (IVIG) with or without prednisone is the most effective, evidence
based antenatal treatment for subsequent FNAIT-affected pregnancies. IVIG
infusion causes hemolysis in other settings, the degree depending upon patient
blood groups (BGs). STUDY DESIGN AND METHODS: In ClinicalTrials.gov NCT00194987,
102 pregnant women received randomized antenatal treatment: Arm A received 2
g/kg/week IVIG; Arm B received 1 g/kg/week IVIG + 0.5 mg/kg/day prednisone. This
post hoc analysis explored BG and anemia in 69 FNAIT mothers treated with Arm A
or Arm B without salvage treatment to explore the effects of IVIG and steroid
treatment on development of anemia in these women. Mothers whose treatment
changed, for example, those with insufficient or unknown fetal PLT response who
received salvage therapy, were excluded. RESULTS: For Arm A, 17 of 21 (hemoglobin
[Hb] < 10 g/dL) mothers with anemia but only three of 15 mothers without anemia
had BG-A and/or BG-B (p = 0.0005). BG was unrelated to anemia in Arm B; only nine
of 33 Arm B mothers became anemic during treatment. The mean decrease in Hb level
in women with BG-non-O was 1.9 g/dL and in women with BG-O was 1.1 g/dL (p =
0.004). Anemia was not caused by iron deficiency; the lowest mean corpuscular
volume was 79. CONCLUSION: FNAIT women with BG-non-O more frequently develop
anemia secondary to high-dose IVIG infusion (2 g/kg/week), quite possibly from
isohemagglutinin-mediated hemolysis; maternal Hb requires monitoring. IVIG at 1
g/kg/week did not cause anemia in women with BG-non-O; concomitant prednisone
likely alleviated the IVIG effect. Maternal BG could influence selection of
antenatal treatment for FNAIT.
PMID- 27611704
TI - High Transferability of Homoeolog-Specific Markers between Bread Wheat and Newly
Synthesized Hexaploid Wheat Lines.
AB - Bread wheat (Triticum aestivum, 2n = 6x = 42, AABBDD) has a complex allohexaploid
genome, which makes it difficult to differentiate between the homoeologous
sequences and assign them to the chromosome A, B, or D subgenomes. The chromosome
based draft genome sequence of the 'Chinese Spring' common wheat cultivar enables
the large-scale development of polymerase chain reaction (PCR)-based markers
specific for homoeologs. Based on high-confidence 'Chinese Spring' genes with
known functions, we developed 183 putative homoeolog-specific markers for
chromosomes 4B and 7B. These markers were used in PCR assays for the 4B and 7B
nullisomes and their euploid synthetic hexaploid wheat (SHW) line that was newly
generated from a hybridization between Triticum turgidum (AABB) and the wild
diploid species Aegilops tauschii (DD). Up to 64% of the markers for chromosomes
4B or 7B in the SHW background were confirmed to be homoeolog-specific. Thus,
these markers were highly transferable between the 'Chinese Spring' bread wheat
and SHW lines. Homoeolog-specific markers designed using genes with known
functions may be useful for genetic investigations involving homoeologous
chromosome tracking and homoeolog expression and interaction analyses.
PMID- 27611705
TI - Novel metrics for risk stratification with nuclear cardiology.
AB - Risk prediction through integration of clinical variables and imaging data into a
prognostic model can identify those factors with a high impact on patient
outcome. The development of a prognostic model traditionally includes the
evaluation of the independent contribution of variables with consideration of
covarying factors that may confound risk stratification. Several methods and
metrics are available to assess the performance of a prediction model.
Traditional measures for binary and survival outcomes include the concordance (C)
statistic for discriminative ability, and goodness-of-fit statistics for
calibration. Different prognostic approaches, including variants of the C
statistic for survival data, reclassification tables, net reclassification
improvement, and integrated discrimination improvement have been recently
proposed to evaluate the contribution of new markers when they are added to a
defined risk model and to evaluate how these variables are able to change the
class of risk of the patient and the resulting diagnostic and therapeutic
managements. Moreover, decision-analytic measures including decision curves
analysis have been introduced to assess the net benefit obtained by making
clinical decisions based on model predictions. This review provides an overview
of various metrics available for risk stratification using nuclear cardiology
procedures, underlying the need of choosing the appropriate prognostic model in
order to justify the referral decision.
PMID- 27611706
TI - Critical appraisal of appropriateness in nuclear cardiology.
AB - Radionuclide myocardial perfusion imaging (MPI) is a large component of the
healthcare spending both in developed and developing countries. MPI is also
responsible for a significant increase in the exposition of patients and health
care operators to ionizing radiations for medical purposes. Thus, health-care
systems and pertinent scientific societies were involved in developing criteria
to contain the non-appropriate use by implementing Appropriate Use Criteria and
Clinical Indications Guidelines. The present manuscript will review the concept
and limitations of such an approach.
PMID- 27611707
TI - Systemic and inflammatory disorders involving the heart: the role of PET imaging.
AB - Cardiac inflammatory disorders, either primarily cardiac or secondary to a
systemic process, are associated with significant morbidity and/or mortality.
Their diagnosis can be challenging, especially due to significant overlap in
their clinical presentation with other cardiac diseases. Recent publications have
investigated the potential diagnostic role of positron emission tomography (PET)
imaging in these patients. Most of the available literature is focused on
Fluorine-18 fluorodeoxyglucose (FDG), a tracer which has already demonstrated its
use in other inflammatory and infectious processes. PET imaging can help in the
diagnosis, prognosis and follow-up in a variety of cardiac inflammatory
processes, including infective endocarditis, cardiac implantable electronic
device infection, pericarditis, myocarditis, sarcoidosis and amyloidosis. PET's
ability to depict metabolic changes and abnormalities, sometime even before the
onset of any anatomical changes, can be a significant advantage over standard
anatomical imaging. PET appears to be particularly useful in cases where standard
investigation is non-diagnostic or equivocal.
PMID- 27611708
TI - Non-invasive measurement of coronary flow reserve: uniqueness of radionuclide
methods and alternative techniques.
AB - Over the last several decades, radionuclide Myocardial Perfusion Imaging (MPI)
has been a mainstay for the evaluation of coronary artery disease (CAD), based on
the assumption that a detailed knowledge of stenosis localization and severity is
not sufficient for clinical decision making. Furthermore, radionuclide MPI
diagnostic accuracy has been implemented by the assessment of Coronary Flow
Reserve (CFR) and Myocardial Blood Flow (MBF), as quantitative indexes of
stenosis severity and surrogates of total ischaemic burden. Several
considerations indicate that these measurement actually improve description of
coronary physiology with respect to conventional qualitative image analysis.
However, several alternative approaches have been optimized and increasingly
proposed to achieve this task in the clinical setting. The aim of the present
narrative review is to discuss strengths and weaknesses of the various cardiac
modalities proposed to define CFR and MBF in the era of multi-modality imaging.
PMID- 27611709
TI - Positron-emission tomography myocardial blood flow quantification in hypertrophic
cardiomyopathy.
AB - In the setting of hypertrophic cardiomyopathy (HCM), ischemia plays a possibly
under-evaluated role. In particular, a large body of evidence indicates that
structural and functional abnormalities in the coronary microcirculation
contribute to myocardial ischemia and are key elements for HCM pathophysiology
and clinical evolution. Measurement of myocardial blood flow (MBF) at rest and
under maximal hyperemia (hMBF) by means of perfusion positron-emission tomography
(PET) is the most effective way to assess microvascular dysfunction in humans.
Therefore, hMBF abnormalities reflect HCM severity and correlate with other
important features, such as ischemic symptoms and myocardial fibrosis. Most
importantly, it has been demonstrated that severely blunted hMBF implies an
adverse outcome in HCM patients. Therefore, PET could be helpful for stratifying
patient prognosis and should be used in selected patient subsets to identify
those at risk of unfavorable evolution.
PMID- 27611710
TI - Clinical relevance of PET myocardial blood flow quantification.
AB - Until a few years ago, myocardial perfusion imaging (MPI) using positron-emission
tomography (PET) and the absolute quantification of myocardial blood flow (MBF)
was limited to research institutions. Following an increase in the number of PET
scanner installations and in the availability of perfusion tracers that do not
have to be produced by an on-site cyclotron and commercial software for MBF
quantification, a more widespread clinical use of MBF quantification with PET can
be expected. This article aims to provide a comprehensive overview of the
advantages of MBF quantification with PET highlighting the potential applications
in several clinical settings, from patients with cardiovascular risk factors and
early coronary artery disease (CAD) to patients with multi-vessel or myocardial
disease. Finally, using current evidence, the independent and incremental
prognostic information of MBF quantification with PET in addition to the visual
interpretation of MPI will also be described.
PMID- 27611711
TI - An update on technical and methodological aspects for cardiac PET applications.
AB - Positron emission tomography (PET) is indicated for a large number of cardiac
diseases: perfusion and viability studies are commonly used to evaluate coronary
artery disease; PET can also be used to assess sarcoidosis and endocarditis, as
well as to investigate amyloidosis. Furthermore, a hot topic for research is
plaque characterization. Most of these studies are technically very challenging.
High count rates and short acquisition times characterize perfusion scans while
very small targets have to be imaged in inflammation/infection and plaques
examinations. Furthermore, cardiac PET suffers from respiratory and cardiac
motion blur. Each type of studies has specific requirements from the technical
and methodological point of view, thus PET systems with overall high performances
are required. Furthermore, in the era of hybrid PET/computed tomography (CT) and
PET/Magnetic Resonance Imaging (MRI) systems, the combination of complementary
functional and anatomical information can be used to improve diagnosis and
prognosis. Moreover, PET images can be qualitatively and quantitatively improved
exploiting information from the other modality, using advanced algorithms. In
this review we will report the latest technological and methodological
innovations for PET cardiac applications, with particular reference to the state
of the art of the hybrid PET/CT and PET/MRI. We will also report the most recent
advancements in software, from reconstruction algorithms to image processing and
analysis programs.
PMID- 27611712
TI - PET imaging of the autonomic nervous system.
AB - The autonomic nervous system is the primary extrinsic control of heart rate and
contractility, and is subject to adaptive and maladaptive changes in
cardiovascular disease. Consequently, noninvasive assessment of neuronal activity
and function is an attractive target for molecular imaging. A myriad of targeted
radiotracers have been developed over the last 25 years for imaging various
components of the sympathetic and parasympathetic signal cascades. While routine
clinical use remains somewhat limited, a number of larger scale studies in recent
years have supplied momentum to molecular imaging of autonomic signaling.
Specifically, the findings of the ADMIRE HF trial directly led to United States
Food and Drug Administration approval of 123I-metaiodobenzylguanidine (MIBG) for
Single Photon Emission Computed Tomography (SPECT) assessment of sympathetic
neuronal innervation, and comparable results have been reported using the
analogous PET agent 11C-meta-hydroxyephedrine (HED). Due to the inherent capacity
for dynamic quantification and higher spatial resolution, regional analysis may
be better served by PET. In addition, preliminary clinical and extensive
preclinical experience has provided a broad foundation of cardiovascular
applications for PET imaging of the autonomic nervous system. Recent years have
witnessed the growth of novel quantification techniques, expansion of multiple
tracer studies, and improved understanding of the uptake of different
radiotracers, such that the transitional biology of dysfunctional subcellular
catecholamine handling can be distinguished from complete denervation. As a
result, sympathetic neuronal molecular imaging is poised to play a role in
individualized patient care, by stratifying cardiovascular risk, visualizing
underlying biology, and guiding and monitoring therapy.
PMID- 27611713
TI - Emergency Department Visits Following Joint Replacement Surgery in an Era of
Mandatory Bundled Payments.
AB - OBJECTIVES: The Center for Medicare & Medicaid Services (CMS) is actively testing
bundled payments models. This study sought to identify relevant details for 90
day postdischarge emergency department (ED) visits of Medicare beneficiaries
following total joint replacement (TJR) surgery meeting eligibility for a CMS
bundled payment program. METHODS: The CMS research identifiable file for the
State of Texas for 2011-2012 was used to identify patients who underwent TJR.
Qualifying inpatient claims were linked to 90-day postdischarge ED claims. The
claims associated with live discharge were divided into three cohorts: elective
total hip replacement (THR), emergent (THR), and total knee replacement. The
frequency, distribution, diagnoses, and disposition for these ED visits were
identified and stratified by timing within the postdischarge period as well as
discharge diagnosis. Visits were correlated with age, sex, joint replaced, and
fracture. RESULTS: There were 50,838 TJR surgeries in Texas in 2011-2012 that
would have been eligible for inclusion in the CMS defined CJR program. A total of
12,747 ED visits by 9,299 patients occurred in the 90-day postdischarge period.
Visits to the ED by patients 85 and older predominated in the case of THR
performed secondary to a hip fracture. Patients 65-74 years predominated in both
elective surgery categories. There were 2,370 ED visits within 90 days of 10,786
elective THRs, of which 55.5% were discharged home, 34.6% were hospitalized or
transferred, and 6.9% were admitted to observation. Of the 3,438 ED visits among
8,475 emergent hip replacement cases, 22.4% were discharged home, 50.2% were
hospitalized or transferred, and 5.3% were admitted to observation. Of the 6,939
visits among 31,387 knee replacement cases, 61.9% were discharged home, 30.6%
were readmitted or transferred, and 7.1% were admitted to observation. The
discharge diagnoses varied by volume and timing in the postdischarge period. The
most prevalent diagnoses across groups included injury/trauma, physiologic
decompensation, cardiopulmonary events, and infection. CONCLUSIONS: ED services
are frequent for Medicare TJR bundle-eligible patients within the postdischarge
period. ED utilization, discharge diagnosis and disposition varied by age, and
elective and emergent surgeries. The ED is an important site for identifying and
managing postoperative adverse outcomes.
PMID- 27611714
TI - Dual Role of Zirconium Oxoclusters in Hybrid Nanoparticles: Cross-Linkers and
Catalytic Sites.
AB - Organic-inorganic hybrid nanoparticles are prepared by free-radical
copolymerization of methyl methacrylate (MMA) with the structurally well-defined
methacrylate-functionalized zirconium oxocluster Zr4O2(methacrylate)12. The
polymerization process occurs in the confined space of miniemulsion droplets. The
formation of covalent chemical bonds between the organic and the inorganic
counterparts improves the distribution of the guest species (oxoclusters) in the
polymer particles, overcoming problems related to migration, leaching, and
stability. Because of the presence of a high number of double bonds (12 per
oxocluster), the oxoclusters act as efficient cross-linking units for the
resulting polymer matrix, thus ruling its swelling behavior in organic solvents.
The synthesized hybrid nanostructures are applied as heterogeneous systems in the
catalytic oxidation of an organic sulfide to the corresponding sulfoxide and
sulfone by hydrogen peroxide, displaying quantitative sulfide conversion in 4-24
h, with overall turnover numbers (TON) up to 8000 after 4 cycles.
PMID- 27611716
TI - Postpolymerization modification of a hydroxy monolith precursor. Part III.
Activation of poly(hydroxyethyl methacrylate-co-pentaerythritol triacrylate)
monolith with epoxy functionalities followed by bonding of glycerol, polyamines,
and hydroxypropyl-beta-cyclodextrin for hydrophilic interaction and chiral
capillary electrochromatography.
AB - In this last part of the series of investigations involving the
postpolymerization modification of a hydroxy monolith (OHM) capillary column, the
surface hydroxyl groups were first reacted with glycerol diglycidyl ether in the
presence of boron trifluoride (BF3 ) to convert the surface into epoxy activated
OHM. The column thus activated with epoxy functions was further functionalized
with polar compounds such as glycerol and polyamines to yield polyol OHM and
polyamine OHM columns, respectively, for use in hydrophilic interaction
electrochromatography. In another postpolymerization functionalization of the
epoxy-activated OHM, hydroxypropyl-beta-CD (HP-beta-CD) was grafted onto the
epoxy OHM surface to produce HP-beta-CD OHM for enantioseparation by CEC (chiral
CEC). The polyol OHM capillary column and polyamine OHM capillary columns
exhibited the typical hydrophilic interactions columns vis-a-vis polar solutes
such as phenolic compounds and nucleobases. The HP-beta-CD OHM column was able to
resolve some racemic compounds as well as positional isomers. All the columns
exhibited good reproducibility from run to run, day to day, and column to column.
PMID- 27611715
TI - In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with
Multiple Sclerosis.
AB - Interleukin 4 (IL-4) can improve the clinical manifestations in experimental
autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS).
Sodium benzoate (NaB) deviates the cytokine profile to Th2 (or IL-4 producing)
cells in EAE and thus might be effective in the treatment of MS. Therefore, in
this study the effect of different concentrations of NaB on the percentage and
mRNA levels of IL-4 and interferon gamma (IFN-gamma)-producing peripheral blood
mononuclear cells (PBMCs) of 20 Relapsing-remitting multiple sclerosis (RR-MS)
patients and eight healthy controls was evaluated in the presence of mitogen
(phytohemagglutinin, PHA) or specific antigen (myelin basic protein, MBP). Our
results showed that in the patient's group the percentage of CD4(+)IL-4(+) cells
was significantly increased in the presence of all concentrations of NaB when
PBMCs were stimulated by MBP (p = 0.001) or PHA (p < 0.03). The same results were
obtained for normal donors in the highest concentration of NaB, 1000 ug/ml (p =
0.02). Moreover, in the patient's group the percentage of CD4(+)IFN-gamma(+)
cells was decreased significantly when the PBMCs were stimulated by PHA and NaB
(p < 0.004) or by MBP and 1000 ug/ml of NaB (p < 0.03). The effect of NaB on IL-4
and IFN-gamma production was also documented at the mRNA levels. In conclusion,
our data suggest that NaB is able to induce IL-4 production by human PBMCs and
therefore might be a useful candidate for conjunctive therapy in RR-MS.
PMID- 27611717
TI - Exciton-Vibrational Couplings in Homo- and Heterodimer Stacks of Perylene
Bisimide Dyes within Cyclophanes: Studies on Absorption Properties and
Theoretical Analysis.
AB - The optical properties of a series of three cyclophanes comprising either
identical or different perylene bisimide (PBI) chromophores were studied by
UV/Vis absorption spectroscopy and their distinctive spectral features were
analyzed. All the investigated cyclophanes show significantly different
absorption features with respect to the corresponding constituent PBI monomers
indicating strong coupling interactions between the PBI units within the
cyclophanes. DFT calculations suggest a pi-stacked arrangement of the PBI units
at close van der Waals distance in the cyclophanes with rotational displacement.
Simulations of the absorption spectra based on time-dependent quantum mechanics
properly reproduced the experimental spectra, revealing exciton-vibrational
coupling between the chromophores both in homo- and heterodimer stacks. The PBI
cyclophane comprising two different PBI chromophores represents the first example
of a PBI heterodimer stack for which the exciton coupling has been investigated.
The quantum dynamics analysis reveals that exciton coupling in heteroaggregates
is indeed of similar strength as for homoaggregates.
PMID- 27611718
TI - Quantile association for bivariate survival data.
AB - Bivariate survival data arise frequently in familial association studies of
chronic disease onset, as well as in clinical trials and observational studies
with multiple time to event endpoints. The association between two event times is
often scientifically important. In this article, we examine the association via a
novel quantile association measure, which describes the dynamic association as a
function of the quantile levels. The quantile association measure is free of
marginal distributions, allowing direct evaluation of the underlying association
pattern at different locations of the event times. We propose a nonparametric
estimator for quantile association, as well as a semiparametric estimator that is
superior in smoothness and efficiency. The proposed methods possess desirable
asymptotic properties including uniform consistency and root-n convergence. They
demonstrate satisfactory numerical performances under a range of dependence
structures. An application of our methods suggests interesting association
patterns between time to myocardial infarction and time to stroke in an
atherosclerosis study.
PMID- 27611720
TI - Thermal Stability of CuSCN Hole Conductor-Based Perovskite Solar Cells.
AB - Although perovskite solar cells (PSCs) surpassing 20 % in certified power
conversion efficiency (PCE) have been demonstrated with organic hole-transporting
layers (HTLs), thermal degradation remains one of the key issues for practical
applications. We fabricated PSCs using low temperature solution-processed CuSCN
as the inorganic hole-transport layer (HTL), which possesses a highly stable
crystalline structure and is robust even at high temperatures. The best
performing cell delivers a PCE of 18.0 %, with 15.9 % measured at the stabilized
power output. Here we report the thermal stability of PSCs based on CuSCN in
comparison with commonly used 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)
9,9'-spirobifluorene (spiro-OMeTAD). The PSC fabricated with organic spiro-OMeTAD
degrades to 25 % of initial PCE after annealing for 2 h at 125 degrees C in air
under 40 % average relative humidity. However, CuSCN-based PSCs maintain
approximately 60 % of the initial value, exhibiting superior thermal stability
under identical conditions. This work demonstrates that high efficiency and
improved thermal stability are simultaneously achieved when CuSCN is used as an
HTL in PSCs.
PMID- 27611719
TI - Contractile capability of the diaphragm assessed by ultrasonography predicts
nocturnal oxygen saturation in COPD.
AB - BACKGROUND AND OBJECTIVE: Diaphragm function might be useful to predict nocturnal
oxygen desaturation in COPD. Ultrasonography has been widely used for the
assessment of the diaphragm. We aimed to investigate the relationship between the
contractile capability of the diaphragm assessed by ultrasonography and the
nocturnal percutaneous arterial oxygen saturation (NSpO2 ) in COPD. METHODS:
Twenty-eight male patients with COPD (age, 73 +/- 7 years; forced expiratory
volume in 1 s (FEV1 ), 54.2 +/- 17.0% predicted) were included. The thickness of
the diaphragm (Tdi) was assessed by ultrasonography. We calculated the change
ratio of Tdi at the end of maximal inspiration and expiration (%DeltaTdi). The
mean value of NSpO2 (NSpO2mean ), the percentage of total sleep time (TST) with
desaturation above 4% (DA4%) and the percentage of TST with saturation below 90%
(SB90%) were measured by overnight oximetry. Daytime arterial oxygen pressure
(PaO2 ) and maximal inspiratory mouth pressure (PImax ) were also measured.
RESULTS: All participants had mild or no daytime hypoxaemia (PaO2 , 77.3 +/- 8.6
mm Hg). The NSpO2mean , DA4% and SB90% were significantly correlated with
%DeltaTdi, PaO2 , %PImax of the predicted value and the Global Initiative for
Chronic Obstructive Lung Disease (GOLD) stage. The %DeltaTdi and PaO2 were
predictors of NSpO2 mean by multiple regression analysis. CONCLUSION: This study
suggested a close relationship between the NSpO2 and the contractile capability
of the diaphragm assessed by ultrasonography in COPD. The %DeltaTdi combined with
PaO2 might predict NSpO2 in COPD patients with mild or no daytime hypoxaemia.
PMID- 27611721
TI - Low Pressure is Necessary to View and to Protect Corona Mortis During Totally
Extraperitoneal Hernia Repair.
AB - BACKGROUND: The identification of retropubic vasculature is not easy under the
pressure of insufflated gas during totally extraperitoneal (TEP) inguinal
hernioplasty. We aimed to present the usefulness of a maneuver that allows the
clear identification of retropubic vasculature. METHODS: Vascular anatomy on the
retropubic surface in 364 patients who underwent the TEP procedure from January
2005 to September 2015 was evaluated. In patients after July 2014, the pressure
in the workspace was decreased from 14 to 8 mmHg before fixation of the mesh to
clearly identify the veins. The results before and after July 2014 were compared.
RESULTS: Demographic features were not significantly different between two
periods. The number of hemipelvises in the first and second periods was 398 and
77, respectively. The rate of identification of venous corona mortis was 31% in
the second period, whereas it was 1.0% in the first period (P = .000). The
identification of thick (5.5% versus 10.3%; P = .123) and thin (22.8% versus
36.3%; P = .014) arterial structures and their sum were increased in the second
period (28.4% versus 46.7%; P = .002). The rate of retropubic bleeding was zero
in the second period, while it was 1.5% in the first period. CONCLUSIONS: During
TEP hernioplasty, the pressure of insufflated gas more than 10 mmHg in the
preperitoneal space hinders the correct identification of vessels on the
retropubic surface. The proposed maneuver, to decrease the pressure in the
workspace to 8 mmHg, can provide clear identification of all vessels, which
decreases the potential risk of vascular injury.
PMID- 27611722
TI - The landscape of systematic reviews in urology (1998 to 2015): an assessment of
methodological quality.
AB - OBJECTIVES: To assess the quality of published systematic reviews in the urology
literature (an extension of our previously reported work), as high-quality
systematic reviews play a paramount role in informing evidence-based clinical
practice. MATERIALS AND METHODS: Our focus was on systematic reviews in the
urology literature that incorporated questions of prevention and therapy. To
identify such reviews published during a 36-month period (2013-2015), we
systematically searched PubMed and hand-searched the table of contents of four
major urology journals. Two reviewers independently assessed the methodological
quality of those reviews, using the 11-point 'Assessment of Multiple Systematic
Reviews' (AMSTAR) instrument. We performed protocol-driven analyses of the data
from our present study's 36-month period alone, as well as in aggregate with the
data from our previously reported work's study periods (2009-2012 and 1998-2008).
RESULTS: In our literature search of the 36-month period (2013-2015), we
initially identified 490 possibly relevant reviews, of which 125 met our
inclusion criteria. The most common topic of reviews for the 2013-2015 period was
oncology (51.2%; n = 64), followed by voiding dysfunction (21.6%; n = 27). The
mean [standard deviation (SD)] AMSTAR score in the 2013-2015 period (n = 125) was
4.8 (2.4); 2009-2012 (n = 113), 5.4 (2.3); and 1998-2008 (n = 57), 4.8 (2.0) (P =
0.127). In the 2013-2015 period, the mean (SD) AMSTAR score for the BJU
International (n = 25) was 5.6 (2.9); for The Journal of Urology (n = 20), 5.1
(2.6); for European Urology (n = 60), 4.5 (2.2); and for Urology (n = 20), 4.4
(2.2) (P = 0.106). CONCLUSIONS: The number of systematic reviews published in the
urology literature has exponentially increased, year by year, but their
methodological quality has stagnated. To enhance the validity and impact of
systematic reviews, all authors and editors must apply established methodological
standards.
PMID- 27611723
TI - The International Mood Network (IMN) Nosology Project: differentiating borderline
personality from bipolar illness.
AB - OBJECTIVE: The differential diagnosis of bipolar illness vs. borderline
personality is controversial. Both conditions manifest impulsive behavior,
unstable interpersonal relationships, and mood symptoms. This study examines
whether and which mood clinical features can differentiate between both
conditions. METHOD: A total of 260 patients (mean +/- standard deviation age 41
+/- 13 years, 68% female) attending to a mood clinic were examined for diagnosis
of bipolar illness and borderline personality disorder using SCID-I, SCID-II, and
clinical mood criteria extracted from Mood Disorder Questionnaire (MDQ). They
were analyzed using diagnoses as dependent variables. Predictors of bipolar and
borderline diagnoses were identified by multivariable logistic regressions, and
predictive validity of models was assessed using ROC curve analysis. RESULTS:
Bipolar illness was strongly predicted by elevated mood (OR = 4.02, 95% CI: 1.80
9.15), increased goal-directed activities (OR = 3.90, 95% CI: 1.73-8.96), and
episodicity of mood symptoms (OR = 3.48, 95% CI 1.49-8.39). This triad model
predicted bipolar illness with 88.7% sensitivity, 81.4% specificity, and obtained
an auROC of 0.91 (95% CI: 0.76-0.96) and a positive predictive value of 85.1%.
For borderline personality disorder, only female gender was a statistically
significant predictor (OR = 3.41, 95% CI: 1.29-13.7), and the predictive model
obtained an auROC of 0.67 (95% CI: 0.53-0.74). CONCLUSION: In a mood disorder
clinic setting, manic criteria and episodic mood course distinguished bipolar
illness from borderline personality disorder.
PMID- 27611725
TI - Time-Resolved Detection of Surface Oxide Formation at Individual Gold
Nanoparticles: Role in Electrocatalysis and New Approach for Sizing by
Electrochemical Impacts.
AB - Nanoparticle (NP) impacts on electrode surfaces has become an important method
for analyzing the properties and activity of individual NPs, by either (i)
electrocatalytic reactions or (ii) volumetric (dissolution) analyses. Using Au
NPs as an exemplar system, this contribution shows that it is possible to detect
surface oxide formation at individual NPs, which can occur on a rapid time scale
(few MUs). The charge associated with this "surface oxidation method" can be used
for sizing (with results that are comparable to TEM) despite charges of only fC
being measured. This platform further allows the role of surface oxides in
electrocatalysis to be elucidated, with the time scale of oxide formation being
controllable (i.e., "tunable") via the applied potential, as illustrated through
studies of borohydride and hydrazine electro-oxidation. Finally, all of these
studies are carried out on an oxide-covered Au substrate, which can be prepared
and regenerated straightforwardly on an Au electrode, through the applied
potential.
PMID- 27611724
TI - ACVIM Small Animal Consensus Recommendations on the Treatment and Prevention of
Uroliths in Dogs and Cats.
AB - In an age of advancing endoscopic and lithotripsy technologies, the management of
urolithiasis poses a unique opportunity to advance compassionate veterinary care,
not only for patients with urolithiasis but for those with other urinary diseases
as well. The following are consensus-derived, research and experience-supported,
patient-centered recommendations for the treatment and prevention of uroliths in
dogs and cats utilizing contemporary strategies. Ultimately, we hope that these
recommendations will serve as a foundation for ongoing and future clinical
research and inspiration for innovative problem solving.
PMID- 27611726
TI - Genetic polymorphisms in the serotonergic system are associated with circadian
manifestations of bruxism.
AB - Bruxism (BRX) is a condition of great interest for researchers and clinicians in
dental and medical areas. BRX has two circadian manifestations; it can occur
during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, WB).
However, it can be suffered together. Recent investigations suggest that central
nervous system neurotransmitters and their genes could be involved in the genesis
of BRX. Serotonin is responsible for the circadian rhythm, maintaining arousal,
regulating stress response, muscle tone and breathing. Thus, serotonin could be
associated with BRX pathogenesis. The aim of this work was to evaluate the
frequency of genetic polymorphisms in the genes HTR1A (rs6295), HTR2A (rs1923884,
rs4941573, rs6313, rs2770304), HTR2C (rs17260565) and SLC6A4 (rs63749047) in
subjects undergoing BRX treatment. Patients included were classified according to
their diagnosis in awake bruxism (61 patients), sleep bruxism (26 patients) and
both (43 patients). The control group included 59 healthy patients with no signs
of BRX. Data showed significant differences in allelic frequencies for the HTR2A
rs2770304 polymorphism, where the C allele was associated with increased risk of
SB (odds ratio = 2.13, 95% confidence interval: 1.08-4.21, P = 0.03). Our results
suggest that polymorphisms in serotonergic pathways are involved in sleep
bruxism. Further research is needed to clarify and increase the current
understanding of BRX physiopathology.
PMID- 27611727
TI - Untargeted Screening and Distribution of Organo-Iodine Compounds in Sediments
from Lake Michigan and the Arctic Ocean.
AB - The majority of halogenated organic compounds present in the environment remain
unidentified. To address this data gap, we recently developed an untargeted
method (data-independent precursor isolation and characteristic fragment; DIPIC
Frag) for identification of unknown organo-bromine compounds. In this study, the
method was adapted to enable untargeted screening of natural and synthetic organo
iodine compounds (NSOICs) in sediments. A total of 4,238 NSOIC peaks were
detected in sediments from Lake Michigan. Precursor ions and formulas were
determined for 2,991 (71%) of the NSOIC peaks. These compounds exhibited
variations in abundances (<10(3) to ~10(7)), m/z values (206.9304-996.9474),
retention times (1.0-29.7 min), and number of iodine atoms (1-4). Hierarchical
cluster analysis showed that sediments in closer proximity exhibited similar
profiles of NSOICs. NSOICs were screened in 10 samples of sediment from the
Arctic Ocean to compare the profiles of NSOICs between freshwater and marine
sediments. A total of 3,168 NSOIC peaks were detected, and profiles of NSOICs in
marine sediments were clearly distinct from Lake Michigan. The coexistence of
brominated and iodinated analogues indicated that some NSOICs are of natural
origin. Different ratios of abundances of iodinated compounds to brominated
analogues were observed and proposed as a marker to distinguish sources of
NSOICs.
PMID- 27611728
TI - Rational derivation of CETP self-binding helical peptides by pi-pi stacking and
halogen bonding: Therapeutic implication for atherosclerosis.
AB - The human cholesteryl ester transfer protein (CETP) transfers cholesteryl ester
from high-density lipoprotein (HDL) to other lipoproteins and has been
established as an attractive target for reducing the risk of atherosclerosis.
Here, an amphipathic alpha-helix peptide, namely SBH-peptide
((465)EHLLVDFLQSLS(476)), was derived from the C-terminal tail of CETP. The
peptide exhibits self-binding capability towards the CETP. Crystal structure
analysis, molecular dynamics (MD) simulations and ab initio electron correlation
characterizations of CETP-SBH-peptide complex system revealed that the Phe471
residue plays a key role in SBH-peptide binding, which can form a pi-pi stacking
with the Phe197 residue of CETP. In addition, substitution of the hydrogen atom
H4 of Phe471 with halogen atoms, in particular the bromine atom Br4, can
constitute a geometrically satisfactory halogen bonding with the oxygen atom O of
CETP Ile193 residue. Fluorescence polarization assays substantiated that (i)
mutation of the aromatic Phe471 to small Ala residue would impair the SBH-peptide
affinity with Kd change from 10.5 to 26.4MUM, indicating that the pi-pi stacking
should exist in Phe471?Phe197 adduct, and (ii) substitution with Br4 can
considerably improve SBH-peptide affinity by ~3-fold, but the SBH-peptide binding
does not change essentially upon substitution with Br3 (a negative control that
is theoretically unable to form the halogen bonding), indicating that the
rationally designed halogen bonding should form between the Phe471(Br4) residue
of SBH-peptide and the Ile193 residue of CETP protein.
PMID- 27611729
TI - Meta-analysis of sentinel lymph node biopsy in breast cancer using the magnetic
technique.
AB - BACKGROUND: The standard for sentinel lymph node biopsy (SLNB), the dual
technique (radiolabelled tracer and blue dye), has several drawbacks. A novel
magnetic technique without these drawbacks has been evaluated in a number of
clinical trials. It uses a magnetic tracer and a handheld magnetometer to
identify and excise sentinel lymph nodes. A systematic review and meta-analysis
was performed to assess the performance and utility of the magnetic in comparison
to the standard technique. METHODS: MEDLINE, PubMed, Embase and the Cochrane
online literature databases were used to identify all original articles
evaluating the magnetic technique for SLNB published up to April 2016. Studies
were included if they were prospectively conducted clinical trials comparing the
magnetic with the standard technique for SLNB in patients with breast cancer.
RESULTS: Seven studies were included. The magnetic technique was non-inferior to
the standard technique (z = 3.87, P < 0.001), at a 2 per cent non-inferiority
margin. The mean identification rates for the standard and magnetic techniques
were 96.8 (range 94.2-99.0) and 97.1 (94.4-98.0) per cent respectively (risk
difference (RD) 0.00, 95 per cent c.i. -0.01 to 0.01; P = 0.690). The total lymph
node retrieval was significantly higher with the magnetic compared with the
standard technique: 2113 (1.9 per patient) versus 2000 (1.8 per patient) (RD
0.05, 0.03 to 0.06; P = 0.003). False-negative rates were 10.9 (range 6-22) per
cent for the standard technique and 8.4 (2-22) per cent for the magnetic
technique (RD 0.03, 0.00 to 0.06; P = 0.551). The mean discordance rate was 3.9
(range 1.7-6.9) per cent. CONCLUSION: The magnetic technique for SLNB is non
inferior to the standard technique, with a high identification rate but with a
significantly higher lymph node retrieval rate.
PMID- 27611730
TI - Subclinical Hypothyroidism in Danish Lean and Obese Children and Adolescents.
AB - OBJECTIVE: Thyroid abnormalities are common in obese children. The aim of the
present study was to examine the prevalence of subclinical hypothyroidism (SH)
and to determine how circulating thyroid hormone concentrations correlate with
anthropometrics in Danish lean and obese children and adolescents. METHODS: In
this cross-sectional study, we included 3006 children and adolescents, aged 6-18
years, from the Registry of the Danish Childhood Obesity Biobank. The
overweight/obese group (n=1796) consisted of study participants with a body mass
index (BMI) standard deviation score (SDS) >=1.28. The control group (n=1210)
comprised lean children with a BMI SDS <1.28. All participants were characterized
by anthropometrics (weight, height, and waist circumference) and fasting serum
concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine, and
free thyroxine (fT4) at baseline. RESULTS: The prevalence of SH was higher among
overweight/obese compared to lean study participants (10.4% vs. 6.4%, p=0.0001).
In the overweight/obese group, fasting serum TSH concentrations were associated
positively with BMI SDS (p<0.0001) and waist-height ratio (WHtR) (p<0.0001)
independent of age, sex, and pubertal developmental stage, whereas fasting serum
fT4 concentrations were associated positively only with WHtR. The odds ratio of
exhibiting SH was 1.8 when being overweight/obese compared with lean (p=0.0007)
and 1.8 when presenting with a WHtR >0.5 (p=0.0003). CONCLUSION: The prevalence
of SH was higher among overweight/obese study participants. The positive
correlations of circulating TSH and fT4 with WHtR suggest that central obesity,
independent of the overall degree of obesity, augments the risk of concurrent
thyroid abnormalities in children and adolescents with obesity.
PMID- 27611731
TI - Development and validation of an LC-MS/MS assay for the quantification of
efavirenz in different biological matrices.
AB - AIM: The non-nucleoside reverse transcriptase inhibitor efavirenz is one of the
most prescribed antiretroviral therapeutics. Efavirenz-containing therapy has
become associated with the occurrence of CNS side effects, including sleep
disturbances, depression and even psychosis. RESULTS: The investigation of
efavirenz distribution required the development of a versatile and sensitive
method. In addition to plasma, quantification was required in brain tissue and
phosphate-buffered saline. The assay presented here was linear from 1.9 to 500
ng/ml. Accuracy and precision ranged between 93.7 and 99.5%, and 1.5 and 5.6%,
respectively. DISCUSSION: The method developed here represents a versatile,
sensitive and easy-to-use assay. The assay has been applied to in vitro and in
vivo samples demonstrating reliable efavirenz quantification in multiple
matrices.
PMID- 27611732
TI - One-Pot Automated Synthesis of Quasi Triblock Copolymers for Self-Healing
Physically Crosslinked Hydrogels.
AB - The preparation of physically crosslinked hydrogels from quasi ABA-triblock
copolymers with a water-soluble middle block and hydrophobic end groups is
reported. The hydrophilic monomer N-acryloylmorpholine is copolymerized with
hydrophobic isobornyl acrylate via a one-pot sequential monomer addition through
reversible addition fragmentation chain-transfer (RAFT) polymerization in an
automated parallel synthesizer, allowing systematic variation of polymer chain
length and hydrophobic-hydrophilic ratio. Hydrophobic interactions between the
outer blocks cause them to phase-separate into larger hydrophobic domains in
water, forming physical crosslinks between the polymers. The resulting hydrogels
are studied using rheology and their self-healing ability after large strain
damage is shown.
PMID- 27611733
TI - New diketopiperazines as vectors for peptide protection and brain delivery:
Synthesis and biological evaluation.
AB - New strategies allowing the transfer of molecules, especially peptides, through
the blood-brain barriers are a major pharmacological challenge for the treatment
of brain diseases. The present study aims at evaluating in vivo the cerebral
bioavailability of carrier systems, based on small and functionalizable 2,5
diketopiperazine (DKP) motifs. We studied 2 different cyclo(Lys-Lys) DKP
scaffolds alone and a cyclo(Lys-Gly) DKP carrier bearing as peptide model, the
tau protein hexapeptide VQIVYK sequence. The different carrier systems were
synthesized and radiolabeled using one of the free domains. The stability,
biodistribution, and ability to cross blood-brain barrier were investigated in
vivo in mice for 99m Tc-DKP scaffolds, 99m Tc-HVQIVYK peptide alone, and 99m Tc
DKP-VQIVYK. 125 I-labelled bovine serum albumin was used as negative control for
brain uptake. Both radiolabeled DKPs scaffolds and 99m Tc-DKP-VQIVYK showed a
high stability, while peptide 99m Tc-HVQIVYK alone was quickly degraded in vivo.
The presence of 99m Tc-DKPs scaffolds and 99m Tc-DKP-VQIVYK was observed in the
ventricular and subarachnoid spaces and to a lower extent in the brain parenchyma
up to 45 minutes post-injection in mice. This work highlights the potentiality of
DKP scaffolds as vectors to transport peptides into the brain by limiting
proteolysis and favoring cerebral bioavailability.
PMID- 27611734
TI - Phylogenetic Placement of a Schistosome from an Unusual Marine Snail Host, the
False Limpet (Siphonaria lessoni) and Gulls (Larus dominicanus) from Argentina
with a Brief Review of Marine Schistosomes from Snails.
AB - In the blood fluke family Schistosomatidae, marine snails are well known as
intermediate hosts. Eight families of marine snails have thus far been reported
to host schistosomes across the world, most of which have been implicated in
human cercarial dermatitis (HCD) outbreaks. As part of our larger effort to
define the species diversity and biology of schistosomes in Argentina, in
particular their role in causing HCD, we searched in the marine pulmonate snail
(Siphonaria lessoni) for a schistosome species described previously from S.
lessoni from southern Argentina. Additionally, gulls (Larus dominicanus)
collected from a different project locality (inland) were examined, because they
are known to spend time in the intertidal regions. Schistosome sporocysts were
found in S. lessoni, and a small worm fragment was retrieved from a gull.
Molecular phylogenies for 28S, ITS1-5.8S-ITS2, and cox1 genes revealed that the
specimens from the gull and S. lessoni grouped closely together, suggesting they
are conspecifics. Also, ITS1-5.8S-ITS2 sequences suggested one of the
schistosomes from S. lessoni and a schistosome from a South African penguin were
also conspecifics. Further study is needed to verify if these specimens comprise
a distinct marine clade within the larger avian schistosome clade that is
comprised mostly of species using freshwater snail hosts. Thus far, it appears
this group of marine schistosomes may be more likely found in the southern
hemisphere. It is unclear if the observed distribution pattern of schistosomes in
Siphonaria is a result of sampling bias and/or indicative of a specific bird
snail-schistosome association. It is clear they are sharply differentiated from
the basal marine clade of avian schistosomes that includes Austrobilharzia.
PMID- 27611735
TI - Batch and fed-batch simultaneous saccharification and fermentation of primary
sludge from pulp and paper mills.
AB - Primary sludge from a Portuguese pulp and paper mill, containing 60% of
carbohydrates, and unbleached pulp (as reference material), with 93% of
carbohydrates, were used to produce ethanol by simultaneous saccharification and
fermentation (SSF). SSF was performed in batch or fed-batch conditions without
the need of a pretreatment. Cellic(r) CTec2 was the cellulolytic enzymatic
complex used and Saccharomyces cerevisiae (baker's yeast or ATCC 26602 strain) or
the thermotolerant yeast Kluyveromyces marxianus NCYC 1426 were employed. Primary
sludge was successfully converted to ethanol and the best results in SSF
efficiency were obtained with S. cerevisiae. An ethanol concentration of 22.7 g L
1 was produced using a content of 50 g L-1 of carbohydrates from primary sludge,
in batch conditions, with a global conversion yield of 81% and a production rate
of 0.94 g L-1 h-1. Fed-batch operation enabled higher solids content (total
carbohydrate concentration of 200 g L-1, equivalent to a consistency of 33%) and
a reduction of three-quarters of cellulolytic enzyme load, leading to an ethanol
concentration of 40.7 g L-1, although with lower yield and productivity. Xylitol
with a concentration up to 7 g L-1 was also identified as by-product in the
primary sludge bioconversion process.
PMID- 27611736
TI - Effects of Pregabalin in Patients with Neuropathic Pain Previously Treated with
Gabapentin: A Pooled Analysis of Parallel-Group, Randomized, Placebo-controlled
Clinical Trials.
AB - OBJECTIVES: This analysis compared the therapeutic response of pregabalin in
patients with neuropathic pain (NeP) who had been previously treated with
gabapentin to the therapeutic response in patients who had not received
gabapentin previously. METHODS: Data were pooled from 18 randomized, double
blind, placebo-controlled trials of pregabalin in patients with NeP. Pregabalin
mediated changes in pain and pain-related sleep interference scores, patient
global impression of change scores at endpoint, and the occurrence of adverse
events were compared between patients who had received gabapentin previously
(+GBN) and patients who had not received gabapentin previously (-GBN). RESULTS:
There were no significant differences between the -GBN and +GBN cohorts with
regard to the extent of pain relief and relief of pain-related sleep interference
for any dose of pregabalin (150, 300, 600, or 150 to 600 mg/day) at any time
point (6, 8, or 12 weeks). Additionally, there was no significant difference in
the distribution of patient global impression of change scores at study endpoint,
or the occurrence of adverse events, between the -GBN and +GBN cohorts.
DISCUSSION: The findings presented here support the idea that pregabalin may be
used successfully to treat patients with NeP who may be refractory, respond
inadequately, or are intolerant to gabapentin. These findings highlight the
importance of tailoring treatment of NeP based on individual patient response to
different treatments, including the trial of multiple agents within the same
mechanistic class.
PMID- 27611737
TI - Revealing the Earth's mantle from the tallest mountains using the Jinping
Neutrino Experiment.
AB - The Earth's engine is driven by unknown proportions of primordial energy and heat
produced in radioactive decay. Unfortunately, competing models of Earth's
composition reveal an order of magnitude uncertainty in the amount of radiogenic
power driving mantle dynamics. Recent measurements of the Earth's flux of
geoneutrinos, electron antineutrinos from terrestrial natural radioactivity,
reveal the amount of uranium and thorium in the Earth and set limits on the
residual proportion of primordial energy. Comparison of the flux measured at
large underground neutrino experiments with geologically informed predictions of
geoneutrino emission from the crust provide the critical test needed to define
the mantle's radiogenic power. Measurement at an oceanic location, distant from
nuclear reactors and continental crust, would best reveal the mantle flux,
however, no such experiment is anticipated. We predict the geoneutrino flux at
the site of the Jinping Neutrino Experiment (Sichuan, China). Within 8 years, the
combination of existing data and measurements from soon to come experiments,
including Jinping, will exclude end-member models at the 1sigma level, define the
mantle's radiogenic contribution to the surface heat loss, set limits on the
composition of the silicate Earth, and provide significant parameter bounds for
models defining the mode of mantle convection.
PMID- 27611738
TI - Molecular epidemiology of Rotavirus A, causing acute gastroenteritis
hospitalizations among children in Nha Trang, Vietnam, 2007-2008: Identification
of rare G9P[19] and G10P[14] strains.
AB - Rotavirus A (RVA) causes acute diarrhea in children as well as animals. As part
of a cross-sectional study of children less than 5 years of age hospitalized for
acute diarrhea in Vietnam during a 15-month period (2007-2008), 322 (43.5%) of
741 fecal specimens contained RVA with 92% either G1P[8] or G3P[8]. This study
was undertaken to further characterize strains that remained untypeable to
complete the G and P genotypes of the 322 rotavirus-positive specimens. While 307
(95.3%) strains possessed the common human RVA genotypes: G1P[8] (45.0%), G2P[4]
(2.8%), G3P[8] (46.9%), and G9P[8] (0.6%), sequencing of initially untypeable
specimens revealed the presence of two unusual strains designated NT0073 and
NT0082 possessing G9P[19] and G10P[14], respectively. The genotype constellation
of NT0073 (G9-P[19]-I5-R1-C1-M1-A8-N1-T7-E1-H1) and the phylogenetic trees
suggested its origin as a porcine RVA strain causing diarrhea in a 24-month-old
girl whereas the genotype constellation of NT0082 (G10-P[14]-I2-R2-C2-M2-A3-N2-T6
E2-H3) and the phylogenetic trees suggested its origin as an RVA strain of
artiodactyl origin (such as cattle, sheep and goats) causing diarrhea in a 13
month-old boy. This study showed that RVA strains of animal host origin were not
necessarily attenuated in humans. A hypothesis may be postulated that P[19] and
P[14] VP4 spike proteins helped the virus to replicate in the human intestine but
that efficient onward human-to-human spread after crossing the host species
barrier may require the virus to obtain some additional features as there was no
evidence of widespread transmission with the limited sampling performed over the
study period. J. Med. Virol. 89:621-631, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27611739
TI - MRI Evaluation of the Urothelial Tract: Pitfalls and Solutions.
AB - OBJECTIVE: MR urography (MRU) can be an alternative to CT urography (CTU) for
imaging of the kidneys, urinary bladder, and collecting systems. MRU can be a
challenging examination to perform and interpret, which may result in technical
and interpretive errors being made. This article highlights the pitfalls
associated with MRU and discusses how to recognize and avoid them. CONCLUSION:
When performed properly, MRU may provide imaging quality generally comparable to
that of CTU, and it enables comprehensive evaluation of the entire urinary tract.
PMID- 27611741
TI - Recovery of fertility in quinestrol-treated or diethylstilbestrol-treated mice:
Implications for rodent management.
AB - Fertility control is an alternative strategy to traditional culling for the
management of rodent pests. Previous studies have demonstrated that quinestrol is
a potential contraceptive for male rodents, but the recovery of fertility in
quinestrol-treated rodents has not been evaluated. This study used C57BL/6J mice
to evaluate the recovery rate of male fertility after the administration of
quinestrol. Diethylstilbestrol (DES), a non-steroid estrogenic compound, was used
for comparison. Different groups of mice were treated with 1 mg/kg quinestrol, 1
mg/kg DES, or castor oil separately for 7 days. These mice were then killed on
days 8, 22 and 50 respectively. Our results indicated that the weight of
epididymides and seminal vesicles decreased significantly on days 8 and 22 in
quinestrol/DES-treated mice, with extensive histological changes in the
seminiferous tubules. Sperm concentrations in the cauda epididymal fluid were
significantly reduced on days 8 and 22 in both quinestrol and DES treatment
groups and on day 50 for the DES, but not the quinestrol group. Further analysis
revealed that DES-treated mice exhibited a higher proportion of abnormal sperm
accumulation in the epididymis, indicating that the normal sperm transportation
to the cauda epididymis was blocked. Our results indicate that the anti-fertility
effects on male mice given quinestrol were of shorter duration than for those
receiving DES at the dose of 1 mg/kg body weight.
PMID- 27611740
TI - Molecular mechanism of male differentiation is conserved in the SRY-absent
mammal, Tokudaia osimensis.
AB - The sex-determining gene SRY induces SOX9 expression in the testes of eutherian
mammals via two pathways. SRY binds to testis-specific enhancer of Sox9 (TESCO)
with SF1 to activate SOX9 transcription. SRY also up-regulates ER71 expression,
and ER71 activates Sox9 transcription. After the initiation of testis
differentiation, SOX9 enhances Amh expression by binding to its promoter with
SF1. SOX8, SOX9 and SOX10, members of the SOXE gene family, also enhance the
activities of the Amh promoter and TESCO. In this study, we investigated the
regulation of these sexual differentiation genes in Tokudaia osimensis, which
lacks a Y chromosome and the SRY gene. The activity of the AMH promoter was
stimulated by SOXE genes and SF1. Mutant AMH promoters, with mutations in its SOX
and SF1 binding sites, did not show significant activity by SOX9 and SF1. These
results indicate that AMH expression was regulated by the binding of SOX9 and
SF1. By contrast, SOXE genes could not enhance TESCO activity. These results
indicate that TESCO enhancer activity was lost in this species. Furthermore, the
activity of the SOX9 promoter was enhanced by ER71, indicating that ER71 may play
an important role in the testis-specific expression of SOX9.
PMID- 27611742
TI - Novel BCR-ABL1 fusion and leukemic mutations of SETBP1, PAX5, and TP53 detected
by next generation sequencing in chronic myeloid leukemia.
AB - Patients with BCR-ABL1 fusion genes are potential candidates for targeted therapy
with tyrosine kinase inhibitor (TKI) imatinib. However, novel BCR-ABL1 fusion
variants can be undetected by qRT-PCR-based routine molecular screening,
affecting immediate patient management and proper treatment selection. In this
study, we describe a case of chronic myeloid leukemia (CML) harboring a novel BCR
ABL1 variant gene. Although Fluorescent In situ Hybridization (FISH) analysis
suggested Philadelphia (Ph) translocation, qRT-PCR screening failed to detect the
presence of a functional fusion transcript, which is critical for selecting
targeted therapy against BCR-ABL1 fusion with aberrant kinase activity.
Meanwhile, G-band cytogenetic analysis was performed twice without a solid
conclusion. To overcome the uncertainty whether TKIs should be used to treat this
patient effectively, we performed whole genome sequencing (WGS) in a next
generation sequencing (NGS) platform and discovered an unusual e13a2-like BCR
ABL1 fusion with 9 ABL1 intron 1 nucleotides incorporated into the broken BCR
exon 13 to form a novel chimeric exon, which has never been described previously
based on the best of our knowledge. Based on FISH and NGS results, the patient
was treated with imatinib, showing significant improvement. Moreover, we also
detected novel genetic mutations in the known leukemic genes SETBP1, PAX5, and
TP53, while their role in the leukemogenesis remains to be determined. In
summary, we have identified BCR-ABL1 fusion and other genetic mutations in a
diagnostically difficult case of CML, demonstrating that NGS is a powerful
diagnostic tool when routine procedures are challenged.
PMID- 27611743
TI - Can the circadian phase be estimated from self-reported sleep timing in patients
with Delayed Sleep Wake Phase Disorder to guide timing of chronobiologic
treatment?
AB - INTRODUCTION: The efficacy of bright light and/or melatonin treatment for Delayed
Sleep Wake Phase Disorder (DSWPD) is contingent upon an accurate clinical
assessment of the circadian phase. However, the process of determining this
circadian phase can be costly and is not yet readily available in the clinical
setting. The present study investigated whether more cost-effective and
convenient estimates of the circadian phase, such as self-reported sleep timing,
can be used to predict the circadian phase and guide the timing of light and/or
melatonin treatment (i.e. dim-light melatonin onset, core body temperature
minimum and melatonin secretion mid-point) in a sample of individuals with DSWPD.
METHOD: Twenty-four individuals (male = 17; mean age = 21.96, SD = 5.11) with
DSWPD were selected on the basis of ICSD-3 criteria from a community-based
sample. The first 24-hours of a longer 80-hour constant laboratory ultradian
routine were used to determine core body temperature minimum (cBTmin), dim-light
melatonin onset (DLMO) and the midpoint of the melatonin secretion period (DLMmid
= [DLM degrees ff-DLMO]/2). Prior to the laboratory session subjective sleep
timing was assessed using a 7-day sleep/wake diary, the Pittsburgh Sleep Quality
Index (PSQI), and the Delayed Sleep Phase Disorder Sleep Timing Questionnaire
(DSPD-STQ). RESULTS: Significant moderate to strong positive correlations were
observed between self-reported sleep timing variables and DLMO, cBTmin and
DLMmid. Regression equations revealed that the circadian phase (DLMO, cBTmin and
DLMmid) was estimated within +/-1.5 hours of the measured circadian phase most
accurately by the combination of sleep timing measures (88% of the sample)
followed by sleep diary reported midsleep (83% of the sample) and sleep onset
time (79% of the sample). DISCUSSION: These findings suggest that self-reported
sleep timing may be useful clinically to predict a therapeutically relevant
circadian phase in DSWPD.
PMID- 27611744
TI - A 5-Year Retrospective Assay of Implant Treatments and Complications in Private
Practice: The Restorative Complications of Single and Short-Span Implant
Supported Fixed Prostheses.
AB - PURPOSE: This report aims to describe the restorative outcome of 5,491 implant
supported single crowns, fixed partial dentures, and splinted restorations that
were prescribed or had implants placed during the study period. Timing of the
complications and the relationship between the complications and different
factors (practitioner, patient, and restoration) are examined. MATERIALS AND
METHODS: Dental clinicians qualified in or before December 2004, registered in
Victoria, and placing and/or restoring implants in private practice were invited
to participate in the study. Data extraction was conducted by two trained and
calibrated research assistants with specific training in implant terminology and
previous research experience extracting data from dental records. Prostheses
average time observed/in function was calculated using the difference between the
definitive restoration date and the patient record examination date or the date
of implant/restoration lost. Both descriptive statistics and generalized linear
mixed modeling were used to describe the restorative complications. RESULTS: Over
the study period a total of 499 mechanical complications were recorded. Single
implant crowns had the largest sample size (n = 4,760) and a recorded
complication rate of 2.56 per 100 prostheses per year. The majority of screw
loosenings recorded in this study were inadequately described. In single-implant
crowns, abutment screw loosening occurred at a rate of 0.07 per 100 per year
while unspecified screw loosening occurred at a rate of 0.53. Lateral screw
loosening was more common in lateral screw-retained implant crowns (1.06) than
decementation was in cement-retained implant crowns (0.57). Esthetics (0.25),
veneer chipping or fracture (0.41), and food packing/contact point issues (0.53)
also represent significant portions of the restorative complications. Each type
of complication presented with a slightly different timing profile. Clustering
within the first year was common. The ratio of screw loosening between the group
who prescribed between 1 and 100 during the study period and those who prescribed
more than 501 implant restorations was 1:0.15 (P = .005). Patients with operator
reported attrition had double the rate of veneer fracture (P = .005). Contact
point issues were approximately three times more common in the posterior segment
(P = .001). CONCLUSION: During the period of January 2005 to December 2009, screw
loosening, lateral screw loosening, decementation, esthetic complication, veneer
chipping or fracture, and food packing/contact point issues were recorded at
different rates for different types of prostheses in the private practices
included in this study. Clusters of several complications within the first year
were observed. For single-implant crowns, screw-loosening complications were less
frequent in the more experienced group. Operator-reported attrition was related
to higher rate of veneering material fracture. More contact point complications
were found in the posterior regions of the oral cavity.
PMID- 27611745
TI - Effect of Double Screw on Abutment Screw Loosening in Single-Implant Prostheses.
AB - PURPOSE: This study was conducted to assess the effect of using a double screw on
the prevention of abutment screw loosening. MATERIALS AND METHODS: Internal
connected abutment with a single screw (IS), internal connected abutment with a
double screw (ID), external connected abutment with a single screw (ES), and
external connected abutment with a double screw (ED) groups were prepared (n = 10
in each group). After 50,000 loading cycles, postload removal torque loss (RTL)
percentage was measured. RESULTS: Postload RTL of ID and ED were smaller than
those of IS and ES (P = .000 and P = .039, respectively). CONCLUSION: This study
showed that a double screw was more effective in prevention of screw loosening.
PMID- 27611746
TI - Osteoradionecrosis Following Carbon Ion Radiotherapy: Case History Report of a
Soft Palate Defect.
AB - Carbon ion radiotherapy, a form of charged particle radiotherapy that has been
used to treat various inoperable and radio-resistant tumors, has been associated
with less severe late effects than conventional radiotherapy. A 63-year-old woman
with a soft palate defect received carbon ion radiotherapy (total dose: 64 Gray
equivalents). Several late effects were observed, and osteoradionecrosis was
observed not only on the tumor side but also on the other side and gradually
expanded during maxillofacial prosthetic rehabilitation. While the definitive
prosthesis improved her speech and eating ability, careful adjustments and close
follow-up should continue with respect to postradiation effects.
PMID- 27611747
TI - Implant- and Tooth-Supported Fixed Prostheses Using a High-Performance Polymer
(Pekkton) Framework.
AB - The type of prosthetic restoration used in implant rehabilitation greatly
contributes to the recovery of masticatory function as well as quality of life in
patients. Frameworks for implant-supported prostheses are typically made by
casting metal or milling either titanium or zirconia. Recently, nonmetal, polymer
type materials were suggested as framework materials. Polyetherketoneketone
(PEKK), a high-performance polymer, was recently introduced in the dental field
with potentially wide-ranging applications. This case history report describes
implant- and tooth-supported fixed prostheses created using a new high
performance polymer (Pekkton, Cendres+Metaux) framework for a fully edentulous
maxilla and partially edentulous mandible.
PMID- 27611748
TI - Effectiveness of Positioning Stents in Radiation-Induced Xerostomia in Patients
with Tongue Carcinoma: A Randomized Controlled Trial.
AB - PURPOSE: The aim of this study was to perform an objective and subjective
evaluation of the efficacy of positioning stents in radiation-induced xerostomia
in patients with tongue carcinoma. MATERIALS AND METHODS: A total of 30 patients
with tongue carcinoma and undergoing conventional radiotherapy were randomly
assigned to control (n = 15) and study (n = 15) groups, without and with a
positioning stent, respectively. Assessment of salivary output reduction was done
before and after radiotherapy, at 3- and 6-month intervals, by measurement of
unstimulated and stimulated salivary flow rates (objective evaluation).
Xerostomia (subjective evaluation) was noted using six items from the Quality of
Life Head and Neck Module (QLQ-H&N35) as proposed by the European Organization
for Research and Treatment of Cancer. The significance level was set at .05.
RESULTS: Mean unstimulated and stimulated salivary flow rates at 3- and 6-month
intervals revealed significantly (P < .05) higher scores for the study group as
compared with the control group. The mean quality of life scores in the study
group were significantly (P < .05) lower compared with the control group.
CONCLUSION: The use of a positioning stent minimized radiation-induced xerostomia
and its symptoms.
PMID- 27611750
TI - The Effect of Edentulous Maxillary Impression Tray Designs When Flabby Tissue Is
Present: An In Vitro Study.
AB - A model with simulated flabby tissue was fabricated by modifying the standard
maxillary edentulous acrylic resin cast to evaluate the effect of maxillary
impression tray design on the displacement of flabby tissue. Seven groups of
trays were fabricated using different combinations of relief spaces and escape
holes. After impression taking, test and control casts were scanned and three
dimensional digital models were superimposed. Negative deviations were recorded
at the point of the alveolar crest, the posterior part of the flabby tissue, and
the middle of the palate, while positive deviations were recorded at the point of
the anterior part of flabby tissue. The amount and characteristics of tissue
displacement differed with tray design and the relief method used.
PMID- 27611749
TI - Root Fracture of Abutment Teeth for Partial Removable Dental Prostheses.
AB - PURPOSE: Root fracture is a common and serious cause of abutment tooth loss. No
studies to date have comprehensively assessed the individual contributions of the
factors that increase stress on abutment teeth. The purpose of this study was to
analyze the stress distribution in abutment teeth based on a three-dimensional
finite element model and to analyze the factors that affect stress distribution.
MATERIALS AND METHODS: Models were generated from the computed tomography data of
a single patient, consisting of a mandibular second premolar abutment tooth,
bone, residual mucous membrane, and a partial removable dental prosthesis (PRDP).
Four models were prepared using different types of endodontic posts and cores.
Akers clasps were used for the simulated PRDPs, and a vertical load was applied
to the occlusal surface of the PRDPs. Debonding between the post and root was
simulated. The Young modulus of the residual ridge was reduced to simulate a poor
fit between the denture base and the residual ridge. Stress distribution in the
abutment tooth root was observed, and the maximum principal stress was evaluated.
RESULTS: The nonmetal post model and the mesial rest model reduced stress
concentration in the root. The stress increased in models simulating debonding
and poor fit. The results of the multiple linear regression analysis confirmed
that debonding and poor fit were significantly associated with root stress.
CONCLUSION: Within the limitations of this study, it is suggested that the
bonding integrity of posts and adequate fit of the denture base are important
factors affecting the longevity of abutment teeth for PRDPs.
PMID- 27611751
TI - Functional and Esthetic Comparison of Metal-Ceramic and All-Ceramic Posterior
Three-Unit Fixed Dental Prostheses.
AB - PURPOSE: The aim of this study was to assess functional and esthetic satisfaction
plus evaluate changes in oral health-related quality of life (OHRQoL) using the
Oral Health Impact Profile (OHIP-14) after insertion of a metal-ceramic (MC-FDP)
or a veneered zirconia all-ceramic (AC-FDP) posterior three-unit fixed dental
prosthesis (FDP). Additionally, patients' and professionals' esthetic evaluations
were compared. MATERIALS AND METHODS: A convenience sample of 34 patients was
randomized to receive a MC-FDP (n = 17) or an AC-FDP (n = 17). Patients were
assessed using the OHIP-14 and also answered a questionnaire regarding
satisfaction with function and esthetics using visual analog scales (VAS) before
treatment and after 2 weeks, after 3 months, and after 1, 2, and 3 years. A fully
dentate control group (n = 20) was also assessed using the OHIP-14. The operator
and another observer evaluated the esthetics of the FDPs using VAS. RESULTS: The
patients assessed the two FDP types similarly for all parameters. In contrast,
there was a statistically significant difference in OHIP-14 results between the
treated patients and the control group before treatment. After treatment, a
statistically significant improvement in OHIP-14 was observed at all
examinations. Patients were highly satisfied with the function and esthetics of
the FDPs. The overall satisfaction with esthetics was statistically significantly
higher among the patients than among the professionals at three out of five
examinations. CONCLUSION: The patients experienced improved OHRQoL and increased
satisfaction with function and esthetics after receiving a posterior three-unit
FDP. No important differences were observed between the two types of FDPs when
evaluated by the patient or the professionals.
PMID- 27611752
TI - Personal Factors Determining Patient Satisfaction with All-Ceramic Crown
Treatment for Single Anterior Teeth.
AB - The Eysenck Personality Questionnaire's (EPQ) N value (neuroticism) was used to
evaluate information from 158 patients before ceramic crown treatment. Patient
satisfaction was also evaluated using a satisfaction questionnaire 2 weeks post
treatment. Patient expectations were not correlated with sex, age, or N value,
and sex was not correlated with patient satisfaction other than in relation to
crown shape. Total esthetic satisfaction and feature improvement were positively
correlated with age, while satisfaction for five specific criteria was negatively
correlated with N value and overall expectation. These observations underscore
the importance of considering the physical and psychologic aspects of patient
care when planning dental treatment.
PMID- 27611753
TI - Association Between Dentition Status and Malnutrition Risk in Serbian Elders.
AB - PURPOSE: The aim of this study was to find the correlation between the number,
type, and placement of symmetric functional tooth units and the nutritional
status using body mass index (BMI) and Mini Nutritional Assessment (MNA) in
patients with both maxillary and mandibular removable partial dentures. MATERIALS
AND METHODS: A randomized study was conducted at the Clinic for Prosthodontics,
School of Dentistry, University of Belgrade, Serbia, followed by determination of
number of functional tooth units. After insertion of the prostheses, the
nutritional status was assessed, using BMI and MNA form. Nutritional status was
reviewed 12 months after prosthetic treatment. Number of teeth and age were
analyzed using analysis of variance and t test. For other variables such as BMI
baseline, BMI follow-up, MNA baseline, MNA follow-up, change in BMI, and change
in MNA, Kruskal-Wallis Test or Mann-Whitney Test were used. RESULTS: The results
on the MNA changes showed that patients with symmetric natural functional tooth
units had significantly higher values (2.9 +/- 0.8) compared with patients
without natural functional tooth units (1.9 +/- 0.6) or with asymmetric natural
functional tooth units (1.6 +/- 0.4). Patients with asymmetric artificial
functional tooth units had significantly lower change in MNA (1.9 +/- 0.4) than
those with symmetric artificial functional tooth units (2.6 +/- 0.9). CONCLUSION:
The findings of this study suggest that adequate rehabilitation with symmetric
positioning of the functional tooth units can improve the nutritional status of
partially edentulous patients.
PMID- 27611754
TI - Tooth Shade-Matching Ability Between Groups of Students with Different Color
Knowledge.
AB - PURPOSE: The aim of this study was to evaluate the effect of gender and knowledge
of color in dentistry on the visual shade-matching ability of dental students
with no experience in shade matching and without identification skills. MATERIALS
AND METHODS: A total of 32 color-normal participants, 16 female (F) and 16 male
(M), completed all phases of the experiment. The control group did not listen to
a 60-minute lecture (FNL = females that did not listen; MNL = males that did not
listen); the other group listened to a lecture about color in dentistry (FL =
females that listened; ML= males that listened). The Toothguide Training Box
(TTB) (VITA Zahnfabrik) was used. The final exam consisted of a total of 15
lightness-chroma-hue tasks. The correct selection of lightness (L*), chroma (C*),
and hue (h*) was observed, as was the computed shade-matching score,
SigmaDeltaE*ab, for each participant. Mann-Whitney U test was used for
statistical analysis of the data (alpha = .05) (SPSS 22.0 for Windows [IBM]).
RESULTS: Gender was found to play an important role in shade matching. The FL
group selected L* better (L* = 12.11) in comparison with the MNL group (L* =
11.00), which is not significantly different (P = .19). The FL group selected L*
better in comparison with the ML group (L* = 10.57), which is not significantly
different (P = .10). The FNL group selected C* statistically significantly better
(C* = 9.86) than did the ML group (C* = 8.57) (P = .016). The shade-matching
score, SigmaDeltaE*ab, for group FL (SigmaDeltaE*ab = 22.50) and group ML
(SigmaDeltaE*ab = 31.79) was marginally statistically significant (P = .06).
CONCLUSION: A 60-minute lecture from the field of color in dentistry has a
minimal impact on tooth-shade matching, whereas gender plays an important role.
PMID- 27611755
TI - Bacterial Contamination of the Internal Cavity of Dental Implants After
Application of Disinfectant or Sealant Agents Under Cyclic Loading In Vitro.
AB - The aim of this in vitro study was to evaluate the influence of two sealants
(Kiero Seal, Kuss Dental, and Berutemp 500, Carl-Bechem) and a disinfectant agent
(Chlorhexamed gel, GlaxoSmithKline) on bacterial colonization of the implant
abutment interface. Implants were pretreated with the substances or left without
sealing before standard abutments were fixed. Half the specimens were subjected
to cyclic loading, and the others were not loaded. Following 7 days of incubation
in a bacterial solution, bacterial counts of the internal part of the implants
were determined by real-time polymerase chain reaction. All pretreatments lowered
bacterial counts, but no substance could guarantee sterility of the implants'
internal portion.
PMID- 27611756
TI - In Vivo Color Relationships Between the Maxillary Central Incisors and Canines as
a Function of Age.
AB - PURPOSE: It has long been taught that the hue of a patient can be taken from the
canine and applied to other anterior teeth at a lower chroma. This concept does
not appear to derive from published work. This study examined color relationships
between in vivo maxillary central incisors and canines as a function of age.
MATERIALS AND METHODS: The L*a*b* values and VITA Classical shades of the
maxillary central incisor and canine of 62 subjects were determined using a
handheld spectrophotometer. Linear regression analysis and t tests were used to
describe the relationships of the L*a*b* values of these teeth within each
patient and as a function of age. RESULTS: Linear regression demonstrated a
significant decrease in DeltaE with age (P = .056). Patient age was greater when
DeltaE (central-canine) > 3.3 (average age = 38.8 years) than when DeltaE < 3.3
(average age = 58.8 years) (t test; P = .19). DeltaC decreases significantly with
age (P < .001). DeltaH demonstrated a trend to decrease as a function of age (P =
.2). DeltaL remained the same over time (P = .21). Changes with age were due to
central incisor differences, while the canine remained constant. CONCLUSION:
DeltaE (incisor-canine) significantly decreases with age; mostly due to DeltaC.
The majority of changes for all three color coordinates are due to alterations in
the central incisor. The majority of the patients in this study were found to
have a different shade family (VITA Classical) for the central incisor and
canine.
PMID- 27611757
TI - Factors Influencing the Dimensional Accuracy of 3D-Printed Full-Coverage Dental
Restorations Using Stereolithography Technology.
AB - PURPOSE: The aim of the present study was to evaluate the effect of the build
angle and the support configuration (thick versus thin support) on the
dimensional accuracy of 3D-printed full-coverage dental restorations. MATERIALS
AND METHODS: A full-coverage dental crown was digitally designed and 3D-printed
using stereolithography-additive manufacturing (SLA-AM) technology. Nine
different angles were used during the build process: 90, 120, 135, 150, 180, 210,
225, 240, and 270 degrees. In each angle, the crown was printed using a thin and
a thick support type, resulting in 18 specimens. The specimens were digitally
scanned using a high resolution optical surface scanner (IScan D104i; Imetric
3D). The dimensional accuracy was evaluated by digital subtraction technique. The
3D digital files of the scanned printed crowns (test model), exported in standard
tessellation language (STL) format, were superimposed with the STL file of the
designed crown (reference model) using Geomagic Studio 2014 (3D Systems).
RESULTS: The root mean square estimate value and color map results suggest that
the build angle and support structure configuration have an influence on the
dimensional accuracy of 3D-printed crown restorations. Among the tested angles,
the 120-degree build angle showed a minimal deviation of 0.029 mm for thin
support and 0.031 mm for thick support, indicating an accurate fit between the
test and reference models. Furthermore, the deviation pattern observed in the
color map was homogenously distributed and located further away from the critical
marginal area. CONCLUSIONS: Within the limitations of this study, the selection
of build angle should offer the crown the highest dimensional accuracy and self
supported geometry. This allows for the smallest necessary support surface area
and decreases the time needed for finishing and polishing. These properties were
mostly observed with a build angle of 120 degrees combined with a thin support
type.
PMID- 27611758
TI - Application of Monolithic Zirconia Ceramics in Dental Practice: A Case History
Report.
AB - Monolithic zirconia restorations increasingly have been used in dental practice
in recent years and demonstrate superior mechanical performance compared with
porcelain-veneered zirconia restorations. Recent advances in manufacturing
technology have made possible the fabrication of translucent monolithic zirconia
ceramics. This case report describes three clinical examples of monolithic
zirconia fixed dental prostheses being used in the anterior and posterior regions
and exhibiting acceptable esthetic results.
PMID- 27611759
TI - A Proposed Methodology to Assess the Accuracy of 3D Scanners and Casts and
Monitor Tooth Wear Progression in Patients.
AB - PURPOSE: The aim of this study was to detail and assess the capability of a novel
methodology to 3D-quantify tooth wear progression in a patient over a period of
12 months. MATERIALS AND METHODS: A calibrated stainless steel model was used to
identify the accuracy of the scanning system by assessing the accuracy and
precision of the contact scanner and the dimensional accuracy and stability of
casts fabricated from three different types of impression materials. Thereafter,
the overall accuracy of the 3D scanning system (scanner and casts) was
ascertained. Clinically, polyether impressions were made of the patient's
dentition at the initial examination and at the 12-month review, then poured in
type IV dental stone to assess the tooth wear. The anterior teeth on the
resultant casts were scanned, and images were analyzed using 3D matching software
to detect dimensional variations between the patient's impressions. RESULTS: The
accuracy of the 3D scanning system was established to be 33 MUm. 3D clinical
analysis demonstrated localized wear on the incisal and palatal surfaces of the
patient's maxillary central incisors. The identified wear extended to a depth of
500 MUm with a distribution of 4% to 7% of affected tooth surfaces. CONCLUSION:
The newly developed 3D scanning methodology was found to be capable of assessing
and accounting for the various factors affecting tooth wear scanning. Initial
clinical evaluation of the methodology demonstrates successful monitoring of
tooth wear progression. However, further clinical assessment is needed.
PMID- 27611760
TI - Four-Year Clinical Evaluation of GFRC-RBFPDs as Periodontal Splints to Replace
Lost Anterior Teeth.
AB - PURPOSE: The aim of this study was to evaluate the clinical performance of glass
fiber-reinforced composite-based resin-bonded fixed partial dentures (GFRC
RBFPDs) as periodontal splints for periodontal support-reduced anterior partially
edentulous dentition and for replacing lost teeth. MATERIALS AND METHODS: A total
of 39 subjects were enrolled who required fixed restorations for lost mandibular
anterior teeth where the adjacent teeth offered severely reduced periodontal
support. GFRC-RBFPDs were cemented to replace the lost teeth and to stabilize the
adjacent teeth. The survival rates were recorded, and the periodontal condition
(bone height, bleeding index, and probing depth) was evaluated at 1, 2, 3, and 4
years after the restorations. The results were statistically analyzed with single
factor variance analysis and chi-square tests (alpha = .05). RESULTS: The
complete survival rate was 89.7%, and the functional survival rate was 92.3% at
the fourth year. The main reason for failure was fracture of the connector of the
GFRC-RBFPDs. In 21.7% of adjacent teeth, the bone height decreased; in the other
78.3%, it increased from 1 year after the restoration to the end of the
observation period and the heights were statistically different from the initial
values. The periodontal condition of the adjacent teeth was improved after the
restoration. CONCLUSIONS: This 4-year clinical evaluation indicated that GFRC
RBFPDs may be useful as fixed prostheses to replace one to three lost anterior
teeth with damaged periodontal support in adjacent teeth.
PMID- 27611761
TI - Experimental and Theoretical Studies of Low-Energy Penning Ionization of NH3 ,
CH3 F, and CHF3.
AB - We present results from a joint theoretical and experimental study of the low
energy Penning ionization of NH3 , CH3 F, and CHF3 by metastable Ne(3 P2 ) and
He(3 S1 ) atoms. We combine the merged neutral beams experiment, covering a range
of collision energies between 0.1-150 K, with multichannel quantum defect theory
calculations based on interaction potentials from symmetry-adapted perturbation
theory. The three symmetric tops provide several distinct properties that make
them interesting targets for cold chemistry studies. Of these three, only NH3 has
a lone electron pair that leads to a strong binding with rare gas atoms. The CHF3
molecule has much smaller rotational constants than both NH3 and CH3 F, and thus
has a considerably higher density of rotational states already at low energies.
Their presence opens inelastic collision channels that reduce the observed
reactive cross section. We show that this effect dominates the total rate
coefficient in heavy molecules already at relatively low collision energies but
is much less prominent for lighter molecules.
PMID- 27611762
TI - The biology of glucagon and the consequences of hyperglucagonemia.
AB - The proglucagon-derived peptide hormone, glucagon, comprises 29 amino acids. Its
secretion from the pancreatic alpha cells is regulated by several factors.
Glucagon increases blood glucose levels through gluconeogenesis and
glycogenolysis. Elevated plasma concentrations of glucagon, hyperglucagonemia,
may contribute to diabetes. However, hyperglucagonemia is also observed in other
clinical conditions than diabetes, including nonalcoholic fatty liver disease,
glucagon-producing tumors and after gastric bypass surgery. Here, we review the
current literature on hyperglucagonemia in disease with a particular focus on
diabetes, and finally speculate that the primary physiological importance of
glucagon may not reside in glucose homeostasis but in regulation of amino acid
metabolism exerted via a hitherto unrecognized hepato-pancreatic feedback loop.
PMID- 27611763
TI - Percutaneous endobiliary RFA combined with balloon-sweep for re-opening occluded
metallic biliary stents.
AB - The aim of this report is to discuss the results of percutaneous endobiliary
radiofrequency ablation (RFA) combined with balloon-sweep technique in restoring
the patency of occluded self-expandable metallic stents (SEMS) secondary to tumor
infiltration. A total of eight patients underwent endobiliary RFA for reopening
of occluded SEMS at our institute. After endobiliary RFA, all patients showed
restoration of stent patency. After a median follow-up of 6.5 months, four
patients had succumbed to the underlying disease at 3, 4, 6, and 7 months. Two of
these required reinterventions at 2 and 5 months. One patient died of sepsis and
aspiration pneumonia at 3 months. Of the remaining three patients, two required
re-intervention after 2 months, while the other remained asymptomatic. The mean
duration of stent patency after the first session of RFA was 4 +/- 2.1 months,
which was comparable to the primary patency of these stents (4.2 months). Our
experience suggests that endobiliary RFA with balloon sweep is a safe and useful
technique for re-establishing the patency of occluded SEMS.
PMID- 27611764
TI - Bienzyme reactions on cross-linked DNA scaffolds for electrochemical analysis.
AB - Enzymes play an essential role in various detection technologies. We show here
that interstrand cross-linked oligodeoxynucleotides (CL-ODNs) can provide stable
scaffolds for efficiently coupling two types of enzymatic reactions on an
electrode. Glucose can be electrochemically detected using glucose oxidase (GOx)
and horseradish peroxidase (HRP). When both GOx and HRP were immobilized on an
electrode surface by attachment at the termini of CL-ODNs, the current value was
markedly increased compared with that obtained on a standard ODN scaffold. The
relative orientation of the enzymes on the electrode strongly affected the
current intensities. The CL-ODN also allowed GOx-HRP to form a complex on the
tiny surface of a microelectrode, resulting in the imaging of local glucose
distribution. These results suggest that CL-ODNs have potential utility in other
sensing technologies.
PMID- 27611766
TI - Expression, regulation and function of intestinal drug transporters: an update.
AB - Although oral drug administration is currently the favorable route of
administration, intestinal drug absorption is challenged by several highly
variable and poorly predictable processes such as gastrointestinal motility,
intestinal drug solubility and intestinal metabolism. One further determinant
identified and characterized during the last two decades is the intestinal drug
transport that is mediated by several transmembrane proteins such as P-gp, BCRP,
PEPT1 and OATP2B1. It is well-established that intestinal transporters can affect
oral absorption of many drugs in a significant manner either by facilitating
their cellular uptake or by pumping them back to gut lumen, which limits their
oral bioavailability. Their functional relevance becomes even more apparent in
cases of unwanted drug-drug interactions when concomitantly given drugs that
cause transporter induction or inhibition, which in turn leads to increased or
decreased drug exposure. The longitudinal expression of several intestinal
transporters is not homogeneous along the human intestine, which may have
functional implications on the preferable site of intestinal drug absorption.
Besides the knowledge about the expression of pharmacologically relevant
transporters in human intestinal tissue, their exact localization on the apical
or basolateral membrane of enterocytes is also of interest but in several cases
debatable. Finally, there is obviously a coordinative interplay of intestinal
transporters (apical-basolateral), intestinal enzymes and transporters as well as
intestinal and hepatic transporters. This review aims to give an updated overview
about the expression, localization, regulation and function of clinically
relevant transporter proteins in the human intestine.
PMID- 27611765
TI - Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related
peptidase 10.
AB - Although kallikrein-related peptidase 10 (KLK10) is expressed in a variety of
human tissues and body fluids, knowledge of its physiological functions is
fragmentary. Similarly, the pathophysiology of KLK10 in cancer is not well
understood. In some cancer types, a role as tumor suppressor has been suggested,
while in others elevated expression is associated with poor patient prognosis.
Active human KLK10 exhibits a unique, three residue longer N-terminus with
respect to other serine proteases and an extended 99-loop nearly as long as in
tissue kallikrein KLK1. Crystal structures of recombinant ligand-free KLK10 and a
Zn2+ bound form explain to some extent the mixed trypsin- and chymotrypsin-like
substrate specificity. Zn2+-inhibition of KLK10 appears to be based on a unique
mechanism, which involves direct binding and blocking of the catalytic triad.
Since the disordered N-terminus and several loops adopt a zymogen-like
conformation, the active protease conformation is very likely induced by
interaction with the substrate, in particular at the S1 subsite and at the
unusual Ser193 as part of the oxyanion hole. The KLK10 structures indicate that
the N-terminus, the nearby 75-, 148-, and the 99-loops are connected in an
allosteric network, which is present in other trypsin-like serine proteases with
several variations.
PMID- 27611769
TI - Debunking the July Effect Myth.
PMID- 27611770
TI - Is Communication Improved With the Implementation of an Obstetrical Version of
the World Health Organization Safe Surgery Checklist?
AB - OBJECTIVE: Communication failures are consistently seen as a root cause of
preventable adverse outcomes in obstetrics. We assessed whether use of an
Obstetric Safe Surgery Checklist for cesarean deliveries (CDs), based on the WHO
Safe Surgery Checklist, can improve communication; reduce team member confusion
about urgency of the case; and decrease documentation discrepancies among
nursing, obstetric, anesthesia, and pediatric staff. METHODS: Retrospective
review of 600 CDs on our 2 labor and delivery suites before and after the
introduction of 2 consecutive versions of our obstetric safe surgery checklist
(100 cases in each cohort) was undertaken. The first version was released in
2010, and after modifications based on initial findings, our current version was
released in 2014. One hundred consecutive CDs were identified from each of the 3
periods at each hospital, and charts for those patients and newborns were
abstracted. Notes by obstetricians, nurses, anesthesiologists, and pediatricians
were reviewed. We compared the rates of agreement in the documentation of the
indication for the CD between the different members of the team. Chi-square
analyses were performed. RESULTS: Complete agreement among the 4 specialties in
the documented indication for CD before introduction of our initial safe surgery
checklist was noted in 59% (n = 118) of cases. After initial checklist
introduction, agreement decreased to 43% (n = 86; P = 0.002). We then modified
our checklist to include indication for CD and level of urgency and changed our
policy to include pediatric staff participation in the timeout. Agreement in a
subsequent chart review increased to 80% (n = 160), significantly better than in
our initial analysis (P < 0.001) and our interim review (P < 0.001). The greatest
improvement in agreement was observed between obstetricians and pediatricians.
CONCLUSIONS: Implementation of a safe surgery checklist can improve communication
at CDs, but care should be taken when implementing checklists because they can
have unanticipated consequences. Ongoing review and modification are critical to
ensure safer medical care.
PMID- 27611767
TI - Recent insights into nitrite signaling processes in blood.
AB - Nitrite was once thought to be inert in human physiology. However, research over
the past few decades has established a link between nitrite and the production of
nitric oxide (NO) that is potentiated under hypoxic and acidic conditions. Under
this new role nitrite acts as a storage pool for bioavailable NO. The NO so
produced is likely to play important roles in decreasing platelet activation,
contributing to hypoxic vasodilation and minimizing blood-cell adhesion to
endothelial cells. Researchers have proposed multiple mechanisms for nitrite
reduction in the blood. However, NO production in blood must somehow overcome
rapid scavenging by hemoglobin in order to be effective. Here we review the role
of red blood cell hemoglobin in the reduction of nitrite and present recent
research into mechanisms that may allow nitric oxide and other reactive nitrogen
signaling species to escape the red blood cell.
PMID- 27611768
TI - A cross-talk between DNA methylation and H3 lysine 9 dimethylation at the KvDMR1
region controls the induction of Cdkn1c in muscle cells.
AB - The cdk inhibitor p57kip2, encoded by the Cdkn1c gene, plays a critical role in
mammalian development and in the differentiation of several tissues. Cdkn1c
protein levels are carefully regulated via imprinting and other epigenetic
mechanisms affecting both the promoter and distant regulatory elements, which
restrict its expression to particular developmental phases or specific cell
types. Inappropriate activation of these regulatory mechanisms leads to Cdkn1c
silencing, causing growth disorders and cancer. We have previously reported that,
in skeletal muscle cells, induction of Cdkn1c expression requires the binding of
the bHLH myogenic factor MyoD to a long-distance regulatory element within the
imprinting control region KvDMR1. Interestingly, MyoD binding to KvDMR1 is
prevented in myogenic cell types refractory to the induction of Cdkn1c. In the
present work, we took advantage of this model system to investigate the
epigenetic determinants of the differential interaction of MyoD with KvDMR1. We
show that treatment with the DNA demethylating agent 5-azacytidine restores the
binding of MyoD to KvDMR1 in cells unresponsive to Cdkn1c induction. This, in
turn, promotes the release of a repressive chromatin loop between KvDMR1 and
Cdkn1c promoter and, thus, the upregulation of the gene. Analysis of the
chromatin status of Cdkn1c promoter and KvDMR1 in unresponsive compared to
responsive cell types showed that their differential responsiveness to the MyoD
dependent induction of the gene does not involve just their methylation status
but, rather, the differential H3 lysine 9 dimethylation at KvDMR1. Finally, we
report that the same histone modification also marks the KvDMR1 region of human
cancer cells in which Cdkn1c is silenced. On the basis of these results, we
suggest that the epigenetic status of KvDMR1 represents a critical determinant of
the cell type-restricted expression of Cdkn1c and, possibly, of its aberrant
silencing in some pathological conditions.
PMID- 27611771
TI - Patient Safety Incidents and Adverse Events in Ambulatory Dental Care: A
Systematic Scoping Review.
AB - BACKGROUND: There have been efforts to understand the epidemiology of iatrogenic
harm in hospitals and primary care and to improve the safety of care provision.
There has in contrast been very limited progress in relation to the safety of
ambulatory dental care. OBJECTIVES: To provide a comprehensive overview of the
range and frequencies of existing evidence on patient safety incidents and
adverse events in ambulatory dentistry. METHODS: We searched MEDLINE and EMBASE
for articles reporting events that could have or did result in unnecessary harm
in ambulatory dental care. We extracted and synthesized data on the types and
frequencies of patient safety incidents and adverse events. RESULTS: Forty
articles were included. We found that the frequencies varied very widely between
studies; this reflected differences in definitions, populations studied, and
sampling strategies. The main 5 PSIs we identified were errors in diagnosis and
examination, treatment planning, communication, procedural errors, and the
accidental ingestion or inhalation of foreign objects. However, little attention
was paid to wider organizational issues. CONCLUSIONS: Patient safety research in
dentistry is immature because current evidence cannot provide reliable estimates
on the frequency of patient safety incidents in ambulatory dental care or the
associated disease burden. Well-designed epidemiological investigations are
needed that also investigate contributory factors.
PMID- 27611772
TI - Adverse Events at Baseline in a Chinese General Hospital: A Pilot Study of the
Global Trigger Tool.
AB - OBJECTIVE: To investigate adverse events (AEs) at baseline in a Chinese general
hospital using the Institute for Healthcare Improvement (IHI) Global Trigger Tool
(GTT) and discuss the feasibility of this tool to detect AEs in China. METHODS: A
total of 10 inpatient records from the hospital were sampled randomly half a
month in 2014. The records were reviewed to identify AEs according to the second
edition of the IHI GTT for measuring AEs. Triggers and AEs were analyzed using
Microsoft Excel 2007. Statistical analyses were performed using IBM SPSS
software, version 19.0. RESULTS: A review of 240 patient records identified 51.0%
(26/51) triggers in the worksheet, and 33.3% (17/51) were associated with AEs. A
total of 70 AEs were identified in 54 patients, including 65.7% (46/70) category
E AEs, which represent temporary harm requiring intervention, and 34.3% (24/70)
category F AEs, which represent temporary harm requiring initial or prolonged
hospitalization. The average rate of AEs per 1000 patient-days was 32.1 +/- 20.9.
The average rate of AEs per 100 admissions was 29.2 +/- 16.1. The average rate of
admissions with an AE was 22.5% +/- 13.9%. The most significant characteristic of
patients with AEs was longer hospital stay. CONCLUSIONS: More than one fifth of
adult inpatients in the current study experienced at least one AE resulting in
temporary harm, most commonly caused by surgical operations and medication. With
some modifications, the IHI GTT is a feasible and effective tool for detecting
the overall status of AEs in a Chinese hospital.
PMID- 27611774
TI - Structure Revision of an Acorane Sesquiterpene Cordycepol A.
AB - Structure revision of a recently reported spirodecane sesquiterpene, cordycepol
A, from fungi Cordyceps ophioglossoides was enabled by fast and accurate
calculations of nuclear spin-spin coupling constants (SSCCs) with a relativistic
force field (DU8c) parametric method. Two other reported cordycepols, B and C,
are also identified as misassigned. Calculations of accurate SSCCs, which contain
a wealth of structural information, offer a chemically intuitive tool for
structure elucidation, rendering the whole structure revision process more guided
and intentional, while augmenting in a synergistic way the calculations of
chemical shifts.
PMID- 27611773
TI - GPR40 mediates potential positive effects of a saturated fatty acid enriched diet
on bone.
AB - SCOPE: The stimulation of the free fatty acid receptor G-protein coupled receptor
(GPR) 40 by GW9508 prevents bone loss by inhibiting osteoclast activity, both in
vitro and in vivo. Here, we questioned whether the stimulation of the GPR40
receptor by dietary fatty acids may lead to the same beneficial effect on bone.
METHODS AND RESULTS: We investigated (i) the impact of a fatty acid enriched diet
(high-fat diet [HFD]) on bone health in C57/BL6 female mice depending on (ii) the
estrogen status (ovariectomy) and (iii) the genotype (GPR40+/+ or GPR40-/- ).
Bone mineral density (BMD), body composition, weight, inflammation and bone
remodeling parameters were monitored. HFD decreased BMD in HFD-SH-GPR40+/+ mice
but OVX failed to further impact BMD in HFD-OVX-GPR40+/+ mice, while additional
bone loss was observed in HFD-OVX-GPR40-/- animals. These data suggest that when
stimulated by fatty acid enriched diets GPR40 contributes to counteract
ovariectomy-induced bone alteration. The sparing effect is supported by the
modulation of both the osteoprotegerin/receptor activator of nuclear factor kappa
B ligand (OPG/RANKL) ratio in blood stream and the expression level of
inflammatory markers in adipose tissues. Bone preservation by GPR40 stimulation
is dependent on the presence of long-chain saturated fatty acids. CONCLUSION:
GPR40 contributes to counter ovariectomy-induced bone loss in a context of
saturated fatty acid enrichment.
PMID- 27611775
TI - Body composition of obese adolescents: association between adiposity indicators
and cardiometabolic risk factors.
AB - BACKGROUND: The association between obesity during adolescence and the increased
risk of cardiometabolic diseases indicates the need to identify reproducible and
cost effective methods for identifying individuals who are at increased risk of
developing diseases. The present cross-sectional study investigated the
occurrence of metabolic consequences of obesity in adolescents and the use of
adiposity indicators as predictors of cardiometabolic risk. METHODS: A fasting
blood sample was taken in 93 pubertal obese adolescents aged 13-18 years old (39
males, 54 females) for the assessment of cardiometabolic risk markers (glucose,
lipid profiles, insulin resistence, and inflammatory and endothelial dysfunction
markers). Together with anthropometry, total fat mass and lean mass were
determined by dual-energy X-ray absorptiometry (DXA). RESULTS: The prevalence of
dyslipidaemia and disorders in glucose metabolism are noticeably higher in the
present study. There was no correlation between the percentage of body fat
according to DXA and most indicators of adiposity. For boys, the arm
circumference values predicted the increase in fasting insulin (r2 = 0.200),
homeostasis model assessment of insulin resistance (r2 = 0.267) and
cardiometabolic risk score (r2 = 0.338). The percentage of body fat according to
DXA predicted the inflammation score (r2 = 0.172). For girls, body mass index was
the parameter that best described the variability of fasting insulin (r2 = 0.079)
and inflammation score (r2 = 0.263). The waist-to-stature ratio was able to
predict the triglyceride values (r2 = 0.090). CONCLUSIONS: Anthropometric
measures of adiposity, such a body mass index, waist-to-stature ratio, arm
circumference and waist circumference,should be considered in the clinical
evaluation of obese adolescents.
PMID- 27611777
TI - HIV Self-Testing among Men Who Have Sex with Men (MSM) in the UK: A Qualitative
Study of Barriers and Facilitators, Intervention Preferences and Perceived
Impacts.
AB - INTRODUCTION: Innovative strategies, such as HIV self-testing (HIVST), could
increase HIV testing rates and diagnosis. Evidence to inform the design of an
HIVST intervention in the UK is scarce with very little European data on this
topic. This study aims to understand values and preferences for HIVST
interventions targeting MSM in the UK. We explore the acceptability of HIVST
among MSM in the context of known barriers and facilitators to testing for HIV;
assess preferences for, and the concerns about, HIVST. METHODS: Six focus group
discussions (FGD) were conducted with 47 MSM in London, Manchester and Plymouth.
HIVST as a concept was discussed and participants were asked to construct their
ideal HIVST intervention. OraQuickTM and BioSureTM kits were then demonstrated
and participants commented on procedure, design and instructions. FGDs were
recorded and transcribed verbatim, then analysed thematically. RESULTS:
Convenience and confidentiality of HIVST was seen to facilitate testing. Issues
with domestic privacy problematised confidentiality. HIVST kits and instructions
were thought to be unnecessarily complicated, and did not cater to the required
range of abilities. The window period was the most important element of an HIVST,
with strong preference for 4th generation testing. Kits which used a blood sample
were more popular than those using saliva due to higher perceived accuracy
although phobia of needles and/or blood meant some would only access HIVST if a
saliva sample option was available. A range of access options was important to
maintain convenience and privacy. HIVST kits were assumed to increase frequency
of testing, with concerns related to the dislocation of HIVST from sexual health
care pathways and services. DISCUSSION: Utility of HIVST arises from relatively
high levels of confidentiality and convenience. Until 4th generation assays are
available HIVST will be seen as supplementary in a UK context.
PMID- 27611776
TI - Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir +/-
dasabuvir +/- ribavirin in hepatitis C: AMBER study.
AB - BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir +/
dasabuvir +/- ribavirin (OBV/PTV/r +/- DSV +/- RBV) therapy have shown high
sustained virologic response (SVR) rates and good tolerability in most patient
populations in pre-registration studies. AIM: To confirm these clinical trial
findings in the treatment of genotype 1 and 4 hepatitis C under real-world
conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r +/- DSV +/-
RBV based on therapeutic guidelines were included, and the regimen was
administered according to product characteristics. Clinical and laboratory data,
including virologic response, were collected at baseline, end of treatment (EOT)
and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C
were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver
cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and
84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207
(99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B
and post-orthotopic liver transplantation patients achieved SVR. Adverse events
occurred in 151 (72.2%) patients and were mostly mild and associated with the use
of RBV. Serious adverse events, including hepatic decompensation, renal
insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight
(3.8%) patients. In five (2.4%) patients, adverse events led to treatment
discontinuation. On-treatment decompensation was experienced by seven (3.3%)
patients. CONCLUSIONS: The results of our study confirm previous findings. They
demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r+/-
DSV+/-RBV in HCV genotype 1-infected patients treated in the real-world setting.
PMID- 27611778
TI - Inoculation density and nutrient level determine the formation of mushroom-shaped
structures in Pseudomonas aeruginosa biofilms.
AB - Pseudomonas aeruginosa often colonises immunocompromised patients and the lungs
of cystic fibrosis patients. It exhibits resistance to many antibiotics by
forming biofilms, which makes it hard to eliminate. P. aeruginosa biofilms form
mushroom-shaped structures under certain circumstances. Bacterial motility and
the environment affect the eventual mushroom morphology. This study provides an
agent-based model for the bacterial dynamics and interactions influencing
bacterial biofilm shape. Cell motility in the model relies on recently published
experimental data. Our simulations show colony formation by immotile cells.
Motile cells escape from a single colony by nutrient chemotaxis and hence no
mushroom shape develops. A high number density of non-motile colonies leads to
migration of motile cells onto the top of the colonies and formation of mushroom
shaped structures. This model proposes that the formation of mushroom-shaped
structures can be predicted by parameters at the time of bacteria inoculation.
Depending on nutrient levels and the initial number density of stalks, mushroom
shaped structures only form in a restricted regime. This opens the possibility of
early manipulation of spatial pattern formation in bacterial colonies, using
environmental factors.
PMID- 27611779
TI - CaMKII-Mediated CREB Phosphorylation Is Involved in Ca2+-Induced BDNF mRNA
Transcription and Neurite Outgrowth Promoted by Electrical Stimulation.
AB - Electrical stimulation (ES)-triggered up-regulation of brain-derived neurotrophic
factor (BDNF) and neurite outgrowth in cultured rat postnatal dorsal root
ganglion neurons (DRGNs) is calcium (Ca2+)-dependent. The effects of increased
Ca2+ on BDNF up-regulation and neurite outgrowth remain unclear. We showed here
that ES increased phosphorylation of the cAMP-response element binding protein
(CREB). Blockade of Ca2+ suppressed CREB phosphorylation and neurite outgrowth.
Down-regulation of phosphorylated (p)-CREB reduced BDNF transcription and neurite
outgrowth triggered by ES. Furthermore, blockade of calmodulin-dependent protein
kinase II (CaMKII) using the inhibitors KN93 or KN62 reduced p-CREB, and specific
knockdown of the CaMKIIalpha or CaMKIIbeta subunit was sufficient to suppress p
CREB. Recombinant BDNF or hyperforin reversed the effects of Ca2+ blockade and
CaMKII knockdown. Taken together, these data establish a potential signaling
pathway of Ca2+-CaMKII-CREB in neuronal activation. To our knowledge, this is the
first report of the mechanisms of Ca2+-dependent BDNF transcription and neurite
outgrowth triggered by ES. These findings might help further investigation of
complex molecular signaling networks in ES-triggered nerve regeneration in vivo.
PMID- 27611780
TI - Non-Rigid Registration of Liver CT Images for CT-Guided Ablation of Liver Tumors.
AB - CT-guided percutaneous ablation for liver cancer treatment is a relevant
technique for patients not eligible for surgery and with tumors that are
inconspicuous on US imaging. The lack of real-time imaging and the use of a
limited amount of CT contrast agent make targeting the tumor with the needle
challenging. In this study, we evaluate a registration framework that allows the
integration of diagnostic pre-operative contrast enhanced CT images and intra
operative non-contrast enhanced CT images to improve image guidance in the
intervention. The liver and tumor are segmented in the pre-operative contrast
enhanced CT images. Next, the contrast enhanced image is registered to the intra
operative CT images in a two-stage approach. First, the contrast-enhanced
diagnostic image is non-rigidly registered to a non-contrast enhanced image that
is conventionally acquired at the start of the intervention. In case the initial
registration is not sufficiently accurate, a refinement step is applied using non
rigid registration method with a local rigidity term. In the second stage, the
intra-operative CT-images that are used to check the needle position, which often
consist of only a few slices, are registered rigidly to the intra-operative image
that was acquired at the start of the intervention. Subsequently, the diagnostic
image is registered to the current intra-operative image, using both
transformations, this allows the visualization of the tumor region extracted from
pre-operative data in the intra-operative CT images containing needle. The method
is evaluated on imaging data of 19 patients at the Erasmus MC. Quantitative
evaluation is performed using the Dice metric, mean surface distance of the liver
border and corresponding landmarks in the diagnostic and the intra-operative
images. The registration of the diagnostic CT image to the initial intra
operative CT image did not require a refinement step in 13 cases. For those
cases, the resulting registration had a Dice coefficient for the livers of 91.4%,
a mean surface distance of 4.4 mm and a mean distance between corresponding
landmarks of 4.7 mm. For the three cases with a refinement step, the registration
result significantly improved (p<0.05) compared to the result of the initial non
rigid registration method (DICE of 90.3% vs 71.3% and mean surface distance of
5.1 mm vs 11.3 mm and mean distance between corresponding landmark of 6.4 mm vs
10.2 mm). The registration of the preoperative data with the needle image in 16
cases yielded a DICE of 90.1% and a mean surface distance of 5.2 mm. The
remaining three cases with DICE smaller than 80% were classified as unsuccessful
registration. The results show that this is promising tool for liver image
registration in interventional radiology.
PMID- 27611781
TI - Urinary Microbiota Associated with Preterm Birth: Results from the Conditions
Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE)
Study.
AB - Preterm birth (PTB) is the leading cause of infant morbidity and mortality.
Genitourinary infection is implicated in the initiation of spontaneous PTB;
however, examination of the urinary microbiota in relation to preterm delivery
using next-generation sequencing technologies is lacking. In a case-control study
nested within the Conditions Affecting Neurocognitive Development and Learning in
Early Childhood (CANDLE) study, we examined associations between the urinary
microbiota and PTB. A total of 49 cases (delivery < 37 weeks gestation) and 48
controls (delivery >= 37 weeks gestation) balanced on health insurance type were
included in the present analysis. Illumina sequencing of the 16S rRNA gene V4
region was performed on urine samples collected during the second trimester. We
observed no difference in taxa richness, evenness, or community composition
between cases and controls or for gestational age modeled as a continuous
variable. Operational taxonomic units (OTUs) classified to Prevotella,
Sutterella, L. iners, Blautia, Kocuria, Lachnospiraceae, and S.marcescens were
enriched among cases (FDR corrected p<= 0.05). A urinary microbiota clustering
partition dominated by S. marcescens was also associated with PTB (OR = 3.97, 95%
CI: 1.19-13.24). These data suggest a limited role for the urinary microbiota in
PTB when measured during the second trimester by 16S rRNA gene sequencing. The
enrichment among cases in several organisms previously reported to be associated
with genitourinary pathology requires confirmation in future studies to rule out
the potential for false positive findings.
PMID- 27611782
TI - Bifidobacteria Prevent Tunicamycin-Induced Endoplasmic Reticulum Stress and
Subsequent Barrier Disruption in Human Intestinal Epithelial Caco-2 Monolayers.
AB - Endoplasmic reticulum (ER) stress is caused by accumulation of unfolded and
misfolded proteins in the ER, thereby compromising its vital cellular functions
in protein production and secretion. Genome wide association studies in humans as
well as experimental animal models linked ER stress in intestinal epithelial
cells (IECs) with intestinal disorders including inflammatory bowel diseases.
However, the mechanisms linking the outcomes of ER stress in IECs to intestinal
disease have not been clarified. In this study, we investigated the impact of ER
stress on intestinal epithelial barrier function using human colon carcinoma
derived Caco-2 monolayers. Tunicamycin-induced ER stress decreased the trans
epithelial electrical resistance of Caco-2 monolayers, concomitant with loss of
cellular plasma membrane integrity. Epithelial barrier disruption in Caco-2 cells
after ER stress was not caused by caspase- or RIPK1-dependent cell death but was
accompanied by lysosomal rupture and up-regulation of the ER stress markers
Grp78, sXBP1 and Chop. Interestingly, several bifidobacteria species inhibited
tunicamycin-induced ER stress and thereby diminished barrier disruption in Caco-2
monolayers. Together, these results showed that ER stress compromises the
epithelial barrier function of Caco-2 monolayers and demonstrate beneficial
impacts of bifidobacteria on ER stress in IECs. Our results identify epithelial
barrier loss as a potential link between ER stress and intestinal disease
development, and suggest that bifidobacteria could exert beneficial effects on
this phenomenon.
PMID- 27611783
TI - Differences in Circulating microRNAs between Grazing and Grain-Fed Wagyu Cattle
Are Associated with Altered Expression of Intramuscular microRNA, the Potential
Target PTEN, and Lipogenic Genes.
AB - We aimed to understand the roles of miRNAs in the muscle tissue maturation and
those of circulating microRNAs (c-miRNAs) in beef production of Japanese Black
(JB) cattle (Wagyu), a breed with genetically background of superior
intermuscular fat depot, by comparing different feeding conditions (indoor grain
feeding vs. grazing on pasture). The cattle at 18 months old were assigned to
pasture feeding or conventional indoor grain feeding conditions for 5 months.
Microarray analysis of c-miRNAs from the plasma extracellular vesicles led to the
detection of a total of 202 bovine miRNAs in the plasma, including 15 miRNAs that
differed between the feeding conditions. Validation of the microarray results by
qPCR showed that the circulating miR-10b level in the grazing cattle was
upregulated compared to that of the grain-fed cattle. In contrast, the levels of
miR-17-5p, miR-19b, miR-29b, miR-30b-5p, miR-98, miR-142-5p, miR-301a, miR-374b,
miR-425-5p, and miR-652 were lower in the grazing cattle than in the grain-fed
cattle. Bioinformatic analysis indicated that the predicted target genes of those
c-miRNAs were enriched in gene ontology terms associated with blood vessel
morphogenesis, plasma membrane, focal adhesion, endocytosis, collagen, ECM
receptor interaction, and phosphorylation. In the grazing cattle, the elevation
of miR-10b expression in the plasma was coincident with its elevation in the
longissimus lumborum (LL) muscle. Expression of bovine-specific miR-2478, the
most plasma-enriched miRNA, tended to be also upregulated in the muscle but not
in the plasma. Furthermore, grazing caused the downregulated mRNA expression of
predicted miR-10b and/or miR-2478 target genes, such as DNAJB2, PTEN, and SCD1.
Thus, the feeding system used for JB cattle affected the c-miRNAs that could be
indicators of grain feeding. Among these, miR-10b expression was especially
associated with feeding-induced changes and with the expression of the potential
target genes responsible for glucose homeostasis and intramuscular fat depot in
the LL muscle of JB cattle.
PMID- 27611785
TI - Estimating the Effective Permittivity for Reconstructing Accurate Microwave-Radar
Images.
AB - We present preliminary results from a method for estimating the optimal effective
permittivity for reconstructing microwave-radar images. Using knowledge of how
microwave-radar images are formed, we identify characteristics that are typical
of good images, and define a fitness function to measure the relative image
quality. We build a polynomial interpolant of the fitness function in order to
identify the most likely permittivity values of the tissue. To make the
estimation process more efficient, the polynomial interpolant is constructed
using a locally and dimensionally adaptive sampling method that is a novel
combination of stochastic collocation and polynomial chaos. Examples, using a
series of simulated, experimental and patient data collected using the Tissue
Sensing Adaptive Radar system, which is under development at the University of
Calgary, are presented. These examples show how, using our method, accurate
images can be reconstructed starting with only a broad estimate of the
permittivity range.
PMID- 27611786
TI - Evidence for increased behavioral control by punishment in children with
attention-deficit hyperactivity disorder.
AB - BACKGROUND: The behavioral sensitivity of children with ADHD to punishment has
received limited theoretical and experimental attention. This study evaluated the
effects of punishment on the response allocation of children with ADHD and
typically developing children. METHOD: Two hundred and ten children, 145
diagnosed with ADHD, completed an operant task in which they chose between
playing two simultaneously available games. Reward was arranged symmetrically
across the games under concurrent variable interval schedules. Asymmetric
punishment schedules were superimposed; responses on one game were punished four
times as often as responses on the other. RESULTS: Both groups allocated more of
their responses to the less frequently punished alternative. Response bias
increased significantly in the ADHD group during later trials, resulting in
missed reward trials and reduced earnings. CONCLUSIONS: Punishment exerted
greater control over the response allocation of children with ADHD with increased
time on task. Children with ADHD appear more sensitive to the cumulative effects
of punishment than typically developing children.
PMID- 27611784
TI - Training Reduces Stress in Human-Socialised Wolves to the Same Degree as in Dogs.
AB - The welfare of animals in captivity is of considerable societal concern. A major
source of stress, especially for wild animals, is the lack of control over their
environment, which includes not being able to avoid contact with human beings.
Paradoxically, some studies have shown that interactions with human beings may
improve the welfare of wild animals in captivity. Here, we investigated the
behavioural (behaviours indicative of cooperation or stress) and physiological
(variations in salivary cortisol concentrations) effects of the increasingly used
practice of training wild animals as a way to facilitate handling and/or as
behavioural enrichment. We evaluated the effects of indoor training sessions with
familiar caretakers on nine human-socialised individuals of a wild species, the
wolf (Canis lupus), in comparison to nine individuals of its domesticated form,
the dog (Canis lupus familiaris). All animals were raised and kept in
intraspecific packs under identical conditions-in accordance with the social
structure of the species-in order to control for socialisation with human beings
and familiarity with training. We also collected saliva samples of trainers to
measure GC and testosterone concentrations, to control for the effects of
trainers' stress levels on the responses of the animals. During the training
sessions, separated from pack members, the animals stayed voluntarily close to
the trainers and mostly adequately performed requested behaviours, indicating
concentration to the task. Similarly to dogs, the salivary cortisol level of
wolves-used as an index of stress-dropped during these sessions, pointing to a
similar stress-reducing effect of the training interaction in both subspecies.
The responses to the requested behaviours and the reduction in salivary cortisol
level of wolves and dogs varied across trainers, which indicates that the
relaxing effect of training has a social component. This points to another factor
affecting the welfare of animals during the sessions, beside the rewarding effect
of getting food and control over the situation by successfully completing a task.
As all responses performed by the animals corresponded to cues already familiar
to them, the reported effects were likely due to the above cited factors rather
than to a learning process. Our results support previous findings suggesting that
training is a potentially powerful tool for improving welfare in some wild social
canids by creating structured and positive interactions between these animals and
their human caretakers.
PMID- 27611788
TI - Monitoring of contaminants in recycled paperboard for food contact applications.
AB - BACKGROUND: The lack of harmonized European legislation on food packaging led the
Confederation of European Paper Industries to the proposal of a voluntary
Industry Guideline for the compliance of paper and board materials for food
contact applications. In the present work, a previously established method for
the simultaneous determination of contaminants commonly found in recycled
paperboard was improved and its applicability as a quality control tool in the
paper industry was also assessed. The method involves a sample pre-treatment
followed by gas chromatography/mass spectrometry (GC/MS) analysis. RESULTS: For
analysis, paperboard samples were collected both from three sections of the same
reel and from different reels belonging to the same production run. Results
highlighted no significant differences in terms of contaminant distribution among
samples, which ensured good sampling representativeness. The performance of the
method was considerably improved in terms of linearity range, limits of detection
and quantification (5- to 2-fold lower) by using a quadrupole GC/MS system
instead of an ion trap GC/MS system. CONCLUSION: The proposed method could offer
a key strategy for analysis of benzophenone derivatives, diisopropyl naphthalene
and phthalates in recycled paperboard in order to assess compliance of food
packaging with the voluntary limits recommended by the Industry Guideline. (c)
2016 Society of Chemical Industry.
PMID- 27611787
TI - Titanium and Zirconium Levels Are Associated with Changes in MicroRNAs
Expression: Results from a Human Cross-Sectional Study on Obese Population.
AB - OBJECTIVES: In this study on 90 individuals we aimed at evaluating the microRNAs
(miRNAs) expression profile associated with personal levels of Titanium (Ti) and
Zirconium (Zr) traced in hair samples. Ti and Zr materials are broadly used for
dental implants but the biological reactions triggered by a long term presence of
these materials in the oral cavity still need to be assessed. MiRNAs are
mechanisms that need to be investigated as they play a fundamental role in the
control of gene expression following external stimuli and contribute to a wide
range of pathophysiological processes. METHODS: Using the TaqMan(r) Low-Density
Array, we assessed the expression levels of 377 human miRNAs in peripheral blood
of 90 subjects. Hair samples were analyzed for Ti and Zr content using
Inductively Coupled Plasma-Mass Spectrometry. We performed multivariable
regression analysis to investigate the effects of Ti and Zr exposure on miRNA
expression levels. We used the Ingenuity Pathway Analysis (IPA) software to
explore the functional role of the investigated miRNAs and the related target
genes. RESULTS: Seven miRNAs (miR-99b, miR-142-5p, miR-152, miR-193a-5p, miR-323
3p, miR-335, miR-494) resulted specifically associated with Zr levels. The
functional target analysis showed that miRNAs are involved in mechanisms such as
inflammation, skeletal and connective tissue disorders. CONCLUSIONS: Our data
suggest that Zr is more bioactive than Ti and show that miRNAs are relevant
molecular mechanisms sensitive to Zr exposure.
PMID- 27611789
TI - Microbial Electrosynthesis and Anaerobic Fermentation: An Economic Evaluation for
Acetic Acid Production from CO2 and CO.
AB - Microbial electrosynthesis (MES) and anaerobic fermentation (AF) are two
biological processes capable of reducing CO2, CO, and water into acetic acid, an
essential industrial reagent. In this study, we evaluated investment and
production costs of acetic acid via MES and AF, and compared them to industrial
chemical processes: methanol carbonylation and ethane direct oxidation.
Production and investment costs were found high-priced for MES (1.44 L/kg, 1770
L/t) and AF (4.14 L/kg, 1598 L/t) because of variable and fixed costs and low
production yields (100 t/y) compared to methanol carbonylation (0.26 L/kg, 261
L/t) and ethane direct oxidation (0.11 L/kg, 258 L/t). However, integrating AF
with MES would reduce the release of CO2, double production rates (200 t/y), and
decrease investment costs by 9% (1366 L/t). This resulted into setting the
production costs at 0.24 L/kg which is currently market competitive (0.48 L/kg).
This economically feasible bioprocess produced molar flow rates of 4550 mol per
day from MES and AF independently. Our findings offer a bright opportunity toward
the use and scale-up of MES and AF for an economically viable acetic acid
production process.
PMID- 27611791
TI - Structure and Mechanism of the Sphingopyxin I Lasso Peptide Isopeptidase.
AB - Lasso peptides are natural products that assume a unique lariat knot topology.
Lasso peptide isopeptidases (IsoPs) eliminate this topology through isopeptide
bond cleavage. To probe how these enzymes distinguish between substrates and
hydrolyze only isopeptide bonds, we examined the structure and mechanism of a
previously uncharacterized IsoP from the proteobacterium Sphingopyxis alaskensis
RB2256 (SpI-IsoP). We demonstrate that SpI-IsoP efficiently and specifically
linearizes the lasso peptide sphingopyxin I (SpI) and variants thereof. We also
present crystal structures of SpI and SpI-IsoP, revealing a threaded topology for
the former and a prolyl oligopeptidase (POP)-like fold for the latter. Subsequent
structure-guided mutational analysis allowed us to propose roles for active-site
residues. Our study sheds light on lasso peptide catabolism and expands the
engineering potential of these fascinating molecules.
PMID- 27611790
TI - Comparative Genomics of Acetobacterpasteurianus Ab3, an Acetic Acid Producing
Strain Isolated from Chinese Traditional Rice Vinegar Meiguichu.
AB - Acetobacter pasteurianus, an acetic acid resistant bacterium belonging to alpha
proteobacteria, has been widely used to produce vinegar in the food industry. To
understand the mechanism of its high tolerance to acetic acid and robust ability
of oxidizing ethanol to acetic acid (> 12%, w/v), we described the 3.1 Mb
complete genome sequence (including 0.28 M plasmid sequence) with a G+C content
of 52.4% of A. pasteurianus Ab3, which was isolated from the traditional Chinese
rice vinegar (Meiguichu) fermentation process. Automatic annotation of the
complete genome revealed 2,786 protein-coding genes and 73 RNA genes. The
comparative genome analysis among A. pasteurianus strains revealed that A.
pasteurianus Ab3 possesses many unique genes potentially involved in acetic acid
resistance mechanisms. In particular, two-component systems or toxin-antitoxin
systems may be the signal pathway and modulatory network in A. pasteurianus to
cope with acid stress. In addition, the large numbers of unique transport systems
may also be related to its acid resistance capacity and cell fitness. Our results
provide new clues to understanding the underlying mechanisms of acetic acid
resistance in Acetobacter species and guiding industrial strain breeding for
vinegar fermentation processes.
PMID- 27611792
TI - Accelerated wound healing after wide excisions in Hidradenitis Suppurativa using
autologous split-thickness skin grafting and platelet-rich plasma.
PMID- 27611794
TI - Adelina Anthony Interview with Aimee Carrillo Rowe.
AB - This interview explores how performing artist, activist, writer, director,
performer Adelina Anthony stages queer women of color affects as a complex
terrain to mobilize a decolonial imaginary. Anthony's characters are complex,
contradictory, surly, and resilient with whom audience members connect and feel
deeply. Especially for queer women of color, who rarely get to see their own
experiences on film or on stage, Anthony's work provides a critical forum for
discussing, imagining, naming, and envisioning the connections between our
personal struggles and broader forces of imperialism, heterosexual capitalism,
and settler colonialism. Through the "medicina" of gritty truth-telling and side
splitting laughter, Anthony discusses her own positionality as a coyote
curandera. Through the exploratory genre of the interview, Anthony helps readers
palpably engage a queer woman of color "theory in the flesh" to imagine their own
creative potentialities through a compassionate lens of humility and humor.
PMID- 27611793
TI - Small Molecule-Induced Complement Factor D (Adipsin) Promotes Lipid Accumulation
and Adipocyte Differentiation.
AB - Adipocytes are differentiated by various transcriptional cascades integrated on
the master regulator, Ppargamma. To discover new genes involved in adipocyte
differentiation, preadipocytes were treated with three newly identified pro
adipogenic small molecules and GW7845 (a Ppargamma agonist) for 24 hours and
transcriptional profiling was analyzed. Four genes, Peroxisome proliferator
activated receptor gamma (Ppargamma), human complement factor D homolog (Cfd),
Chemokine (C-C motif) ligand 9 (Ccl9), and GIPC PDZ Domain Containing Family
Member 2 (Gipc2) were induced by at least two different small molecules but not
by GW7845. Cfd and Ccl9 expressions were specific to adipocytes and they were
altered in obese mice. Small hairpin RNA (shRNA) mediated knockdown of Cfd in
preadipocytes inhibited lipid accumulation and expression of adipocyte markers
during adipocyte differentiation. Overexpression of Cfd promoted adipocyte
differentiation, increased C3a production, and led to induction of C3a receptor
(C3aR) target gene expression. Similarly, treatments with C3a or C3aR agonist
(C4494) also promoted adipogenesis. C3aR knockdown suppressed adipogenesis and
impaired the pro-adipogenic effects of Cfd, further suggesting the necessity for
C3aR signaling in Cfd-mediated pro-adipogenic axis. Together, these data show the
action of Cfd in adipogenesis and underscore the application of small molecules
to identify genes in adipocytes.
PMID- 27611795
TI - Correction: RAB-10-Dependent Membrane Transport Is Required for Dendrite
Arborization.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1005484.].
PMID- 27611797
TI - Tuberculosis tenosynovitis with multiple rice bodies of the flexor tendons in the
wrist: A case report.
AB - INTRODUCTION: One of the infectious causes of wrist tenosynovitis is
Mycobacterium tuberculosis. Tendon sheath involvement is rare. Herein, we report
the diagnosis and treatment of a patient with neglected wrist flexor tendon
sheath tuberculosis. PRESENTATION OF CASE: We report the diagnosis and treatment
of a man aged 50 years with neglected wrist flexor tendon sheath tuberculosis.
DISCUSSION: In patients with tendon sheath involvement, symptoms are generally
non-specific such as pain and swelling; therefore, it can be diagnosed late due
to the lack of systemic symptoms. Wrist X-ray imaging in tenosynovitis may show
soft tissue swelling and osteoporotic changes around the wrist joint. T2-weighted
sequences in magnetic resonance imaging are more successful in supporting the
diagnosis. CONCLUSION: M. tuberculosis should be kept in mind as an infectious
agent, especially in developing countries. In order to prevent any delay in
diagnostic evaluation, all steps should be taken carefully.
PMID- 27611796
TI - Extensive ossification of the paraspinal ligaments in a patient with vitamin D
resistant rickets: Case report with literature review.
AB - INTRODUCTION: Ectopic ossification of the spinal ligaments is not uncommon in
patients with Vitamin D-resistant rickets (VDRR), but the long-term consequences
of this condition have not been reported. PRESENTATION OF CASE: The case was a 65
year-old female with VDRR who reported progressive weakness of the upper
extremities, difficulty walking, neck pain, and numbness in the left arm. Imaging
studies demonstrated cord compression with ectopic ossification at the rim of the
occipital bone and OPLL at C1 level. Ankylosis of the whole spine below the C2
vertebra was also noted with preserved mobility only at the craniovertebral
junction. DISCUSSION: Our report showed that ectopic ossification of the spinal
ligament can result in ankylosis of the entire spine in patients with VDRR. In
such patients, the segments with remaining mobility are considered to be at high
risk of developing myelopathy due to increased stress at the junction.
CONCLUSION: The present case underscores the importance of providing long-term
follow-up in VDRR patients presenting with ectopic ossification of the spinal
ligaments. In particular, physicians should pay close attention to the
possibility of myelopathy in any segments with preserved mobility.
PMID- 27611798
TI - Successful treatment of primary advanced gastric plasmacytoma using a combination
of surgical resection and chemotherapy with bortezomib: A case report.
AB - INTRODUCTION: Extramedullary plasmacytoma (EMP) is a plasma cell neoplasm that
presents as a solitary tumor. EMP in the gastrointestinal organs are extremely
uncommon. PRESENTATION OF CASE: A 36-year-old man was admitted to our hospital
with advanced anemia. He had no specific medical history. Gastroendoscopic
findings showed an 8.0-cm submucosal tumor with ulcer on the greater curvature of
the gastric body. Fine-needle aspiration was performed, and the pathologic
diagnosis of the submucosal tumor was a plasmacytoma. Therefore, the patient was
diagnosed with gastric plasmacytoma. A total gastrectomy was performed with
lymphadenectomy. The result of intraoperative peritoneal lavage cytology was
positive. Histological examination revealed serosa-exposed plasmacytoma of the
stomach with lymph nodes metastasis. Additionaly the patient received a three
drug chemotherapy regimen (bortezomib, cyclophosphamide, and dexamethasone [VCD])
from 3 weeks after the operation. After 4 cycles of chemotherapy, the patient
received autologous peripheral blood stem-cell transplantation (auto-PBSCT).
Eighteen months after diagnosis, the patient is in complete remission with no
evidence of local relapse or evolution to multiple myeloma. CONCLUSIONS: This is
the first reported case of advanced gastric plasmacytoma using adjuvant
chemotherapy involving bortezomib and auto-PBSCT after the resection, and the
patient has maintained a good course over a year. This protocol could be a new
way to treat these tumors.
PMID- 27611799
TI - SNP rs1805874 of the Calbindin1 Gene Is Associated with Parkinson's Disease in
Han Chinese.
AB - AIMS: The single-nucleotide polymorphism, rs1805874, in the Calbindin1 gene has
been associated with Parkinson's disease among the Japanese people, but not among
Europeans or Americans. To help clarify these contrasting results, we conducted a
case-control study to explore whether such an association exists among the Han
Chinese. METHODS: We used the ligase detection reaction to genotype the rs1805874
SNP in 514 Han Chinese with Parkinson's disease as well as in 475 healthy Han
Chinese controls. RESULTS: We identified a significant association between the A
allele of rs1805874 and the risk of Parkinson's disease (OR 1.257, 95% CI 1.036
1.524, p = 0.020). Subgroup analysis revealed a significant association of the A
allele with male gender (OR 1.306, 95% CI 1.009-1.691, p = 0.042) and late onset
of disease (OR 1.247, 95% CI 1.010-1.540, p = 0.040). CONCLUSION: Our findings
suggest that the A allele of rs1805874 is associated with risk of Parkinson's
disease among the Han Chinese. Our results, combined with previous studies,
suggest that rs1805874 is associated with Parkinson's disease in East Asians, but
not Caucasians.
PMID- 27611800
TI - Comparative proteomic analyses for elucidating metabolic changes during EPS
production under different fermentation temperatures by Lactobacillus plantarum
Q823.
AB - Exopolysaccharide (EPS)-producing bacteria are of growing interest in industrial
processes, mainly concerning food. Lactic acid bacteria are widely appreciated
for their GRAS (generally recognized as safe) status and their ascertained or
putative probiotic features. Detailed investigation on what happens at metabolic
level during EPS production is scarce in the literature. The facultative
heterofermenter Lactobacillus plantarum Q823 was studied in order to compare
growth and EPS production at 30 degrees C and 37 degrees C. A higher growth rate
was observed at 37 degrees C, whereas, a significantly higher (tenfold increase)
EPS amount was produced at 30 degrees C. To understand the molecular mechanisms
leading to the different EPS production in the two conditions, a comparative
proteomic experiment was performed. The results of the in-gel proteomics revealed
that: i) at 37 degrees C a higher abundance of proteins involved in carbon
catabolism and nucleic acid biosynthesis together with a significant amount of
stress proteins was observed; ii) at 30 degrees C the production of an atypical
manganese-containing non-heme catalase (pseudocatalase) was increased, in
agreement with previous data reporting that growth-rates of catalase negative
Lactobacillus plantarum strains were greater than that of catalase positive
strains. Taken together, all these findings provide further insights about the
metabolic pathways stimulated during EPS production, and the mechanism that
triggers EPS biosynthesis.
PMID- 27611802
TI - Assessment of Hammocks (Petenes) Resilience to Sea Level Rise Due to Climate
Change in Mexico.
AB - There is a pressing need to assess resilience of coastal ecosystems against sea
level rise. To develop appropriate response strategies against future climate
disturbances, it is important to estimate the magnitude of disturbances that
these ecosystems can absorb and to better understand their underlying processes.
Hammocks (petenes) coastal ecosystems are highly vulnerable to sea level rise
linked to climate change; their vulnerability is mainly due to its close relation
with the sea through underground drainage in predominantly karstic soils.
Hammocks are biologically important because of their high diversity and
restricted distribution. This study proposes a strategy to assess resilience of
this coastal ecosystem when high-precision data are scarce. Approaches and
methods used to derive ecological resilience maps of hammocks are described and
assessed. Resilience models were built by incorporating and weighting appropriate
indicators of persistence to assess hammocks resilience against flooding due to
climate change at "Los Petenes Biosphere Reserve", in the Yucatan Peninsula,
Mexico. According to the analysis, 25% of the study area is highly resilient (hot
spots), whereas 51% has low resilience (cold spots). The most significant hot
spot clusters of resilience were located in areas distant to the coastal zone,
with indirect tidal influence, and consisted mostly of hammocks surrounded by
basin mangrove and floodplain forest. This study revealed that multi-criteria
analysis and the use of GIS for qualitative, semi-quantitative and statistical
spatial analyses constitute a powerful tool to develop ecological resilience maps
of coastal ecosystems that are highly vulnerable to sea level rise, even when
high-precision data are not available. This method can be applied in other sites
to help develop resilience analyses and decision-making processes for management
and conservation of coastal areas worldwide.
PMID- 27611801
TI - A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Inducible Factor-1 by
Regulating Mitochondrial Respiration.
AB - We previously reported that hypoxia-inducible factor (HIF)-1 inhibitor LW6, an
aryloxyacetylamino benzoic acid derivative, inhibits malate dehydrogenase 2
(MDH2) activity during the mitochondrial tricarboxylic acid (TCA) cycle. In this
study, we present a novel MDH2 inhibitor compound 7 containing benzohydrazide
moiety, which was identified through structure-based virtual screening of
chemical library. Similar to LW6, compound 7 inhibited MDH2 activity in a
competitive fashion, thereby reducing NADH level. Consequently, compound 7
reduced oxygen consumption and ATP production during the mitochondrial
respiration cycle, resulting in increased intracellular oxygen concentration.
Therefore, compound 7 suppressed the accumulation of HIF-1alpha and expression of
its target genes, vascular endothelial growth factor (VEGF) and glucose
transporter 1 (GLUT1). Moreover, reduction in ATP content activated AMPK, thereby
inactivating ACC and mTOR the downstream pathways. As expected, compound 7
exhibited significant growth inhibition of human colorectal cancer HCT116 cells.
Compound 7 demonstrated substantial anti-tumor efficacy in an in vivo xenograft
assay using HCT116 mouse model. Taken together, a novel MDH2 inhibitor, compound
7, suppressed HIF-1alpha accumulation via reduction of oxygen consumption and ATP
production, integrating metabolism into anti-cancer efficacy in cancer cells.
PMID- 27611804
TI - The ongoing story of the Bacille Calmette-Guerin (BCG) vaccination.
PMID- 27611803
TI - Prenatal Carrier Screening for Spinal Muscular Atrophy.
AB - Introduction Spinal muscular atrophy (SMA), a neurodegenerative genetic disorder,
affects 1:5,000 to 1:10,000 infants. Carrier rates are 1:25 to 1:50. We
implemented ACOG-endorsed prenatal SMA screening in mid-2014 and sought to assess
uptake, observed carrier rate, and providers' knowledge and attitudes toward
genetic conditions and carrier screening. Methods Retrospective cohort study of
all patients receiving prenatal genetic counseling at our institution from August
2014 to April 2015. Factors associated with screening uptake were assessed.
Proportions who accepted screening, were screen-positive, had partners tested,
had partners who were screen-positive, and had fetuses tested were calculated.
Providers' knowledge and attitudes were assessed using a validated questionnaire.
Results Of 1,158 patients offered SMA screening, 224 accepted (19.3%, 95% CI 17.2
21.7). Uptake differed by race, parity, religion, and genetic counselor seen.
Five (2.2% or 1:45, 95% CI 0.8-5.3 or 1:19-1:125) women were identified as
carriers. Of 3 partners screened, none screened positive (0%, 95% CI 0-5.3).
There were no prenatal SMA diagnoses (0%, 95% CI 0-1.4). Of 90 survey
respondents, 42% incorrectly answered 1 of 9 knowledge questions. Provider
attitudes toward screening were contradictory. Conclusion Despite significant
resources utilized, prenatal SMA carrier screening identified no fetal cases.
Cost-effectiveness and other barriers should be considered prior to large-scale
adoption of more comprehensive genetic screening.
PMID- 27611805
TI - Prognostic value of the reactive oxygen species in severe sepsis and septic shock
patients: a pilot study.
AB - BACKGROUND: Reactive oxygen species (ROS) have been shown to play a role in the
pathophysiology of sepsis. The aim of this study was to investigate ROS
production over time in critically ill with sepsis patients and its correlation
with outcome. METHODS: This was a pilot single-centre prospective, observational
study of patients consecutively admitted to our 18-general ICU. Over a period of
6 months all the consecutive patients with recent-onset of severe sepsis or
septic shock were enrolled. Clinical and demographic characteristics of all
patients were recorded. ROMs (ROS metabolites), reduced sulfhydryl groups (SH)
and plasmatic lactate levels were collected at enrollment in the study and then
every 5-7 days over 28 days or until sepsis resolution or death during sepsis.
ROMs were analysed spectrophotometrically by the d-ROMs test (Diacron-Italia). SH
were assayed in plasma by Ellman's reaction by spectrophotometric method. Septic
shock-related mortality was defined as death that occurred during the follow up
period, when the signs of shock remained, and death could not be attributed to
causes other than septic shock by the attending physician. RESULTS: Twenty-five
patients were studied. The SOFA score and the plasmatic lactate levels
significantly correlated with the ROMs plasmatic levels. The mortality rate was
higher in patients whose ROMs plasmatic levels decreased during septic shock
evolution. CONCLUSIONS: Serial measurements of the ROMs plasmatic levels together
with the SOFA score and lactate levels could help to identify septic shock
patients with a very high probability of death.
PMID- 27611806
TI - Propofol versus midazolam for premedication: a placebo-controlled, randomized
double-blinded study.
AB - BACKGROUND: It has been previously reported that subhypnotic doses of propofol
could offer an advantage over midazolam for premedication. This study was
designed to test the hypothesis that a 20 mg IV dose of propofol would be more
effective than a standard 2 mg IV dose of midazolam for reducing acute anxiety
prior to induction of anesthesia. METHODS: One hundred twenty outpatients
scheduled to undergo orthopedic surgery were randomly assigned to one of three
study groups: control (saline); propofol (20 mg); or midazolam (2 mg).
Immediately before administering the study medication, each patient evaluated
their level of acute anxiety and sedation on 11-point verbal rating scales (VRSs)
0=none- 10=highest, and they were also shown a picture. Upon arrival in the OR ~5
min after administering the study medication, anxiety and sedation levels were
reassessed and a second picture was shown. At discharge from the recovery area,
anxiety and sedation levels and their ability to recall the two pictures were
reassessed. RESULTS: Compared to the saline group, both propofol and midazolam
produced significant increases in the patient's level of sedation upon entering
the OR (+2.5+/-2.4 vs. +4.6+/-2.5 and +5.2+/-2.3, respectively [p<0.001]).
Propofol was effective as midazolam compared to saline in reducing the patient's
level of preinduction anxiety (from 3.2+/-2.2 to1.8+/-1.8 vs. 3.1+/-2.2 to 2.3+/
2.1 and 2.7+/-1.8 to 2.8+/-2.1, respectively). Propofol produced more pain on
injection and midazolam significantly reduced recall of the second picture.
CONCLUSIONS: When administered ~5 min prior to entering the OR, propofol, 20mg
IV, was as effective as midazolam 2mg IV in reducing anxiety.
PMID- 27611807
TI - Benefits of Long-Term Pulmonary Rehabilitation Maintenance Program in Patients
with Severe Chronic Obstructive Pulmonary Disease. Three-Year Follow-up.
AB - RATIONALE: In chronic obstructive pulmonary disease (COPD), the benefits of
pulmonary rehabilitation (PR) tend to wane over time. Whether maintenance
techniques may help sustain the benefits achieved after completion of the initial
PR program remains controversial. OBJECTIVES: To determine whether a long-term (3
yr) maintenance program after PR preserves the short-term effects on outcomes in
patients with COPD. METHODS: This was a multicenter prospective randomized trial
including 143 patients with moderate-severe COPD, with 3 years of PR maintenance
following an 8-week outpatient PR program. Patients were randomized to
maintenance intervention group (IG) and standard monitoring program or control
group (CG). The effects on BODE index, 6-minute-walk test distance (6MWD), and
health-related quality of life were compared at 12, 24, and 36 months.
MEASUREMENTS AND MAIN RESULTS: A total of 138 (96.5%) completed the 8-week
program. At this time, all outcomes (BODE, 6MWD, and health-related quality of
life) showed clinically and statistically significant improvements (P <= 0.001).
During the follow-up period, the magnitude of change in 6MWD differed between IG
and CG (P = 0.042), with a slight initial increase in the IG during the first
year and smaller decline afterward. The BODE index changes differed between
baseline and measurements at Month 24 (P = 0.043). At 3 years, the adherence rate
of IG patients was 66% and 17% for the CG group (P < 0.001). CONCLUSIONS: This
study shows a 2-year beneficial effect of a program of rehabilitation maintenance
on the BODE index and 6MWD when compared with a standard strategy. This effect
vanishes after the second year of follow-up. Clinical trial registered with
www.clinicaltrials.gov (NCT 01090999).
PMID- 27611808
TI - Diversity and Similarity of Anesthesia Procedures in the United States During and
Among Regular Work Hours, Evenings, and Weekends.
AB - BACKGROUND: Anesthesiologists providing care during off hours (ie, weekends or
holidays, or cases started during the evening or late afternoon) are more likely
to care for patients at greater risk of sustaining major adverse events than when
they work during regular hours (eg, Monday through Friday, from 7:00 AM to 2:59
PM). We consider the logical inconsistency of using subspecialty teams during
regular hours but not during weekends or evenings. METHODS: We analyzed data from
the Anesthesia Quality Institute's National Anesthesia Clinical Outcomes Registry
(NACOR). Among the hospitals in the United States, we estimated the average
number of common types of anesthesia procedures (ie, diversity measured as
inverse of Herfindahl index), and the average difference in the number of common
procedures between 2 off-hours periods (regular hours versus weekends, and
regular hours versus evenings). We also used NACOR data to estimate the average
similarity in the distributions of procedures between regular hours and weekends
and between regular hours and evenings in US facilities. Results are reported as
mean +/- standard error of the mean among 399 facilities nationwide with weekend
cases. RESULTS: The distributions of common procedures were moderately similar
(ie, not large, <.8) between regular hours and evenings (similarity index .59 +/-
.01) and between regular hours and weekends (similarity index, .55 +/- .02). For
most facilities, the number of common procedures differed by <5 procedures
between regular hours and evenings (74.4% of facilities, P < .0001) and between
regular hours and weekends (64.7% of facilities, P < .0001). The average number
of common procedures was 13.59 +/- .12 for regular hours, 13.12 +/- .13 for
evenings, and 9.43 +/- .13 for weekends. The pairwise differences by facility
were .13 +/- .07 procedures (P = .090) between regular hours and evenings and
3.37 +/- .12 procedures (P < .0001) between regular hours and weekends. In
contrast, the differences were -5.18 +/- .12 and 7.59 +/- .13, respectively, when
calculated using nationally pooled data. This was because the numbers of common
procedures were 32.23 +/- .05, 37.41 +/- .11, and 24.64 +/- .12 for regular
hours, evenings, and weekends, respectively (ie, >2x the number of common
procedures calculated by facility). CONCLUSIONS: The numbers of procedures
commonly performed at most facilities are fewer in number than those that are
commonly performed nationally. Thus, decisions on anesthesia specialization
should be based on quantitative analysis of local data rather than national
recommendations using pooled data. By facility, the number of different
procedures that take place during regular hours and off hours (diversity) is
essentially the same, but there is only moderate similarity in the procedures
performed. Thus, at many facilities, anesthesiologists who work principally
within a single specialty during regular work hours will likely not have
substantial contemporary experience with many procedures performed during off
hours.
PMID- 27611809
TI - Anesthesiologist as Physiologist: Discussion and Examples of Clinical Waveform
Analysis.
PMID- 27611810
TI - Effect of Cytokine Genes in the Pathogenesis and on the Clinical Parameters for
the Treatment of Multiple Myeloma.
AB - In this study, we aimed to explore the association among gene variants of five
cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor
beta-1 (TGF-beta1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and
interleukin-10 (IL-10), and clinical parameters and prognosis in patients with
multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population
for the first time except TNF-alpha. We analyzed five cytokine genes in 113 cases
with MM and 113 healthy controls. Cytokine genotyping was performed by the
polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype
associated with high expression in TNF-alpha gene (-308) variant was found to be
significantly higher (p = 0.019), and GG genotype associated with low expression
in TNF-alpha gene (-308) variant was significantly lower in MM group as compared
with controls (p = 0.012). IFN-gamma (+874) variant TT genotype was increased (p
= 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to
controls. IFN-gamma (+874) T allele was higher in MM patients compared with
controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR =
0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with
5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and
thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival
(EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR =
2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR
= 0.435, p = 0.002) with negative prognostic values. Our results suggested that
TNF-alpha gene (-308) AG genotype and IFN-gamma (+874) TT genotype and T allele
may have a role on MM, while other cytokines were not associated with the risk of
MM.
PMID- 27611811
TI - In Reply to Hauswald.
PMID- 27611812
TI - Opinion of women on emergency obstetric care provided in public facilities in
Lagos, Nigeria: A qualitative study.
AB - Limited attention has been given to opinions of women receiving emergency
obstetric care (EmOC) in developing countries. We organized focus groups with 39
women who received this care from Lagos public facilities. Availability of
competent personnel and equipment were two positive opinions highlighted.
Contrarily, women expressed concerns regarding the seeming unresponsiveness of
the service to nonmedical aspects of care, associated stress of service
utilization, and high treatment costs. There is a need to leverage the positive
perception of women regarding the available technical resources while improving
institutional care components like administrative processes, basic amenities, and
costs toward increasing utilization and preventing complications.
PMID- 27611813
TI - Postpolymerization modification of a hydroxy monolith precursor. Part II. Epoxy
biphenyl modified poly (hydroxyethyl methacrylate-co-pentaerythritol triacrylate)
monolithic capillary columns for reversed-phase capillary electrochromatography
based on pi-pi and hydrophobic interactions.
AB - In this second part of the series of investigations involving the
postpolymerization modification of a hydroxy monolith (OHM) capillary column, the
surface hydroxyl groups were reacted with epoxy biphenyl thus yielding the so
called Biphenyl OHM capillary column. The modification involved the epoxy ring
opening of the 2-biphenylyl glycidyl ether catalyzed by BF3 and its subsequent
reaction with the hydroxyl groups on the OHM precursor surface. The Biphenyl OHM
capillary column thus obtained exhibited the typical reversed phase behavior by
primarily hydrophobic interactions vis-a-vis the homologous series of alkyl
benzenes and in addition by pi-pi interactions toward nitroalkane homologous
series via their pi-electron rich nitro groups. This dual retention mechanism was
very distinctly observed with a set of PAH solutes in the sense that the k values
of the PAH solutes were comparable to those obtained on a more non polar
stationary phase, namely the Epoxy OHM C-16 reported in the preceding article.
Other aromatic solutes showed the dual retention mechanism on the Biphenyl OHM
capillary including phenols, anilines derivatives, and phenoxy acid herbicides.
The Biphenyl OHM capillary exhibited good reproducibility from run-to-run, day-to
day, and column-to-column.
PMID- 27611814
TI - Unraveling the Dual Character of Sulfur Atoms on Sensitizers in Dye-Sensitized
Solar Cells.
AB - Cyclometalated ruthenium sensitizers have been synthesized that differ with
number of thiophene units on the auxiliary ligands. Sensitizers possessing four
(SA25, SA246, and SA285) or none (SA282) sulfur atoms in their structures, were
tested in solar cell devices employing I3-/I- redox mediator, enabling an
estimation of the influence of sulfur-iodine/iodide interactions on dye
sensitized solar cell (DSC) performance. Power conversion efficiencies over 6%
under simulated AM 1.5 illumination (1 Sun) were achieved with all the
sensitizers. Consistently higher open-circuit voltage (VOC) and fill factor (FF)
values were measured using SA282. Scrutinizing the DSCs with these dyes by
transient absorption spectroscopy (TAS) and electrochemical impedance
spectroscopy (EIS) indicate that sulfur atom induced recombination cancels
favorable increased regeneration resulting in decreased power conversion
efficiencies (PCEs). The data indicate that, to reduce charge recombination
channels, the use of sulfur-containing aromatic rings should be avoided if
possible in the dye structure when I3-/I- redox mediator is used.
PMID- 27611815
TI - Weak D antigen expression caused by a novel RHD allele in Argentineans.
PMID- 27611816
TI - Evolutionary Transformation of the Palmaris Longus Muscle in Flying Squirrels
(Pteromyini: Sciuridae): An Anatomical Consideration of the Origin of the
Uniquely Specialized Styliform Cartilage.
AB - A long-standing issue in squirrel evolution and development is the origin of the
styliform cartilage of flying squirrels, which extends laterally from the carpus
to support the gliding membrane (patagium). Because the styliform cartilage is
one of the uniquely specialized structures permitting gliding locomotion, the
knowledge of its origin and surrounding transformation is key for understanding
their aerodynamic evolution. The developmental study that would definitely answer
this question would be difficult due to the rarity of embryological material.
Instead, anatomical examinations have suggested two major hypotheses on the
homology of the styliform cartilage: the pisiform bone of other mammals, or an
additional carpal structure, such as the ulnar sesamoid of some of the other
mammals or the hypothenar cartilage of the non-gliding squirrels. To test these
hypotheses, a detailed examination of the anatomy of the carpus of gliding and
non-gliding squirrels, and the colugo were undertaken. Based on physical and
virtual dissections of the carpus, this study showed that both the pisiform bone
and styliform cartilage were present in flying squirrels. This finding is further
supported by demonstration that a "true Palmaris longus," with innervation
typical for this muscle, inserts on the styliform cartilage. Taken together, our
osteological, muscular, and neurological results suggest that the styliform
cartilage was transformed in flying squirrels from an initially superficial and
ulnar-derived anlagen into its current form. Anat Rec, 300:340-352, 2017. (c)
2016 Wiley Periodicals, Inc.
PMID- 27611817
TI - Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.
AB - Chemical modifications made to hyaluronan to enable covalent crosslinking to form
a hydrogel or to attach other molecules may alter the physical properties as
well, which have physiological importance. Here we created carboxymethyl
hyaluronan (CMHA) with varied degree of modification and investigated the effect
on the viscosity of CMHA solutions. Viscosity decreased initially as modification
increased, with a minimum viscosity for about 30-40% modification. This was
followed by an increase in viscosity around 45-50% modification. The pH of the
solution had a variable effect on viscosity, depending on the degree of
carboxymethyl modification and buffer. The presence of phosphates in the buffer
led to decreased viscosity. We also compared large-scale production lots of CMHA
to lab-scale and found that large-scale required extended reaction times to
achieve the same degree of modification. Finally, thiolated CMHA was disulfide
crosslinked to create hydrogels with increased viscosity and shear-thinning
aspects compared to CMHA solutions.
PMID- 27611819
TI - Propulsion of Active Colloids by Self-Induced Field Gradients.
AB - Previously, metallodielectric Janus particles have been shown to travel with
their dielectric hemisphere forward under low frequency applied electric fields
as a result of asymmetric induced-charge electroosmotic flow. Here, it is
demonstrated that at high frequencies, well beyond the charge relaxation time of
the electric double layer induced around the particle, rather than the velocity
decaying to zero, the Janus particles reverse direction, traveling with their
metallic hemisphere forward. It is proposed that such motion is the result of a
surface force, arising from localized nonuniform electric field gradients,
induced by the dual symmetry-breaking of an asymmetric particle adjacent to a
wall, which act on the induced dipole of the particle to drive net motion even in
a uniform AC field. Although the field is external, since the driving gradient is
induced on the particle level, it may be considered an active colloid. We have
thus termed this propulsion mechanism "self-dielectrophoresis", to distinguish
from traditional dielectrophoresis where the driving nonuniform field is
externally fixed and the particle direction is restricted. It is demonstrated
theoretically and experimentally that the critical frequency at which the
particle reverses direction can be characterized by a nondimensional parameter
which is a function of electrolyte concentration and particle size.
PMID- 27611818
TI - Presumptive Iatrogenic Microcystin-Associated Liver Failure and Encephalopathy in
a Holsteiner Gelding.
AB - An 8-year-old Holsteiner gelding was presented for evaluation of anorexia,
obtundation, icterus, and mild colic signs of 48 hours duration. History,
physical examination, and initial diagnostics were suggestive of hepatic disease
and encephalopathy. Microcystin toxicosis was suspected based on historical
administration of a cyanobacteria supplement, associated serum biochemistry
abnormalities, and characteristic histopathological changes. Microcystin
contamination was confirmed in both supplement containers fed to the horse.
Fulminant hepatic failure and encephalopathy progressed resulting in euthanasia.
Necropsy findings were consistent with microcystin induced liver failure.
PMID- 27611821
TI - Correction to Comment and Response on Synergetic Transformations of Multiple
Pollutants Driven by Cr(VI)-Sulfite Reactions.
PMID- 27611820
TI - Management of Mirizzi Syndrome in Emergency.
AB - INTRODUCTION: Mirizzi syndrome (MS) is a rare complication of cholelithiasis.
Despite the success of laparoscopic cholecystectomy as a minimally invasive
approach to gallstone disease, MS remains a challenge, also for open and robotic
approaches, due to the subverted anatomy of the hepatocystic triangle. Moreover,
when emergency surgery is needed, the optimal preoperative diagnostic assessment
could not be always achievable. We aim to analyze our experience of MS treated in
emergency and to assess the feasibility of a diagnostic and therapeutic
decisional algorithm. METHODS: From March 2006 to February 2016, all patients
with a preoperative diagnosis, or an intraoperative evidence of MS, were
retrospectively analyzed at our Academic Hospital, including patients operated on
in emergency or in deferred urgency. Eighteen patients were included in the study
using exclusion criteria and were treated in elective surgery. RESULTS: The
patients were distributed according to modified Csendes' classification: type I
in 15 cases, type II in 2, type III in 0, type IV in 1, and type V in 0. In the
type I group, diagnosis was intraoperatively performed. Laparoscopic approach was
performed with cholecystectomy or subtotal cholecystectomy, when the hepatocystic
triangle dissection was hazardous. Patients with preoperative diagnosis of acute
abdomen and MS type IV were directly managed by open approach. CONCLUSIONS:
Diagnosis of MS and the therapeutic management of MS are still a challenge,
mostly in an emergency setting. Waiting for standardized guidelines, we propose a
decisional algorithm in emergency, especially in nonspecialized centeres of
hepatobiliary surgery.
PMID- 27611822
TI - Anti-LRP/LR specific antibody IgG1-iS18 significantly impedes adhesion and
invasion in early and late stage colorectal carcinoma cells.
AB - Cancer is a highly complex disease that has become one of the leading causes of
death globally. Metastasis, a major cause of cancer deaths, requires two crucial
events known as adhesion and invasion. The 37kDa/67kDa laminin receptor [laminin
receptor precursor/high-affinity laminin receptor (LRP/LR)] enhances these two
steps, consequently aiding in cancer progression. In this study, the role of
LRP/LR in adhesion and invasion of early (SW-480 & HT-29) and late (DLD-1) stage
colorectal cancer cells has been investigated. Western blotting revealed that
early and late stage colorectal cancer cells contained significantly higher total
LRP/LR levels compared to poorly invasive MCF-7 breast cancer control cells. Flow
cytometry revealed that all three stages of colorectal cancer displayed
significantly higher cell surface LRP/LR levels. Furthermore, upon treatment of
the colorectal cancer cells with the anti-LRP/LR specific antibody IgG1-iS18,
adhesion to laminin-1 was significantly reduced in all three stages. Each stage's
invasive potential was determined using the MatrigelTM invasion assay, which
revealed that invasion is significantly impeded in all three colorectal cancer
stages when the cells are incubated with IgG1-iS18. In addition, Pearson's
correlation coefficients propose that both total and cell surface LRP/LR levels
are directly proportional to the adhesive and invasive potential of all three
stages of colorectal cancer. Hence, these findings indicate the potential for the
use of the IgG1-iS18 antibody as a promising therapeutic tool for colorectal
cancer patients of early and late stage.
PMID- 27611823
TI - APPENDICULAR BIOPSY IN TOTAL COLONIC AGANGLIONOSIS: A HISTOLOGICALLY CHALLENGING
AND INADVISABLE PRACTICE.
AB - : The reliability of intraoperative evaluation of ganglion cells in the appendix
as a guide to a diagnosis of total colonic aganglionosis is unclear. OBJECTIVE:
To evaluate the diagnostic utility of appendicular innervation in colonic
Hirschsprung Disease (HD) and TCA. METHODS: Prospective, systematic study of
ganglion cells and the neural plexii in appendices from cases (HD and TCA) & age
matched controls with frozen & paraffin sections, rapid acetylcholinesterase
(AChE) & immunohistochemistry. RESULTS: 48 appendices (28 controls, 20 cases; 19
frozen) were evaluated. 30 / 48 were neonates. Ganglion cell clusters were
smaller in controls (28) and HD (6) than those in the rectum, distorted at places
and mimicked lymphocytes and endothelial cells, especially in neonates. Complete
study of 13 appendices in TCA showed absence of ganglion cells, hypertrophic
nerves, AChE activity and calretinin staining. . In 2 /13 TCA, an erroneous
frozen section identification of ganglia was later corrected based on AChE
histochemistry and a panel of IHC stains . Ileal biopsies guided the placement of
a ganglionic ileostomy in all. One case each of skip segment aganglionosis in a
TCA & variable hypoganglionosis in long segment colonic HD is reported.
CONCLUSION: Intraoperative characterization of appendicular innervation as a
guide to the diagnosis of TCA is unreliable. ; in part because of the possibility
of skip segment disease / variable hypoganglionosis . We propose terminal ileal
biopsies for diagnosis and leveling of aganglionosis. AChE on frozen / calretinin
on paraffin tissue is the 'best approach' to avoid diagnostic errors.
PMID- 27611824
TI - A comparative study of metal oxide and sulfate catalysts for selective catalytic
reduction of NO with NH3.
AB - The properties and characteristics of metal oxide and sulfate catalysts with
different active elements for selective catalytic reduction of NO with NH3 were
investigated. Cerium-based oxide catalyst showed the widest temperature window
for NO x removal and manganese-based oxide catalyst exhibited the best catalytic
performance at low temperature. For all the catalysts, the SCR activities at low
temperature were directly related with the redox abilities of catalysts. The
existence of sulfate groups inhibited the redox abilities of active species for
sulfate catalysts compared with the metal oxide catalysts. The catalytic
activities of CeWTi-S and MnWTi-S were seriously decreased in contrast to CeWTi-N
and MnWTi-N. The temperature window of CuWTi-S was shifted toward higher
temperature comparing with CuWTi-N. The FeWTi-N and FeWTi-S catalysts both showed
high NO x conversion in the temperature range between 300 degrees C and 400
degrees C and N2O concentrations for iron-based samples were least among the same
kind of catalysts. The abundance of acid sites and weak stability of surface
sulfate groups for iron- and copper-based sulfate catalysts might be the main
reasons accounting for the better NO x conversion in the medium-temperature
range.
PMID- 27611825
TI - Pathological analysis of the prostatic anterior fat pad at radical prostatectomy:
insights from a prospective series.
AB - OBJECTIVE: To assess factors associated with lymphatic drainage and lymph node
(LN) metastasis to the prostatic anterior fat pad (PAFP) in men with prostate
cancer and the utility of routine PAFP analysis at the time of radical
prostatectomy (RP). PATIENTS AND METHODS: Our institution began to prospectively
collect PAFP tissue in 2010. The PAFP was removed at the time of RP and sent as a
pathological specimen separate from the pelvic LNs and prostate. Consecutive RPs
performed at our institution in which the PAFP was removed were reviewed to
determine the rate of LNs in the PAFP, the rate of metastatic LNs in the PAFP,
and the association of metastatic PAFP LN with clinical and pathological
features. The impact on biochemical recurrence (BCR) was assessed with a Cox's
proportional hazard model. RESULTS: In all, 2 413 PAFP specimens were available
for analysis. LNs were found in the PAFP in 255 (10.6%) cases and metastatic LNs
in the PAFPs were found in 14 (0.6%) cases. Metastatic PAFP LNs were associated
with anterior tumours in 11 of the 14 cases (P = 0.01), and were present only in
preoperative D'Amico intermediate- (six of 14) and high- (eight of 14) risk
patients (P < 0.001). Metastatic PAFP LNs were associated with extraprostatic
disease in 13 of the 14 cases, although concomitant pelvic LN involvement was
present in only four of the 14 cases. With a mean follow-up of 1.5 years, three
of the 14 patients with metastatic PAFP LN developed BCR. Positive LN involvement
in either the pelvic LN or PAFP had worse BCR than LN-negative patients (P <
0.001); however, there was no difference in BCR between patients with positive
pelvic LN and positive PAFP LN (P = 0.5). CONCLUSION: Metastatic PAFP LNs are
rare and always occur in the presence of other adverse pathological features. The
routine pathological analysis of PAFP as a separate specimen, especially in low
risk disease, may not be warranted.
PMID- 27611826
TI - Percutaneous Cervical Nucleoplasty vs. Pulsed Radio Frequency of the Dorsal Root
Ganglion in Patients with Contained Cervical Disk Herniation; A Prospective,
Randomized Controlled Trial.
AB - BACKGROUND: Cervical neck pain is often caused by cervical disk pathology and may
cause severe symptoms and disability. Surgeons and patients are increasingly
aware of postsurgery-related complications. This stimulated the clinical usage of
minimally invasive treatments such as percutaneous nucleoplasty (PCN) and pulsed
radio frequency (PRF). However, scientific evidence on both treatments is
limited. OBJECTIVE: Our objective was to evaluate the efficacy of PCN compared to
PRF in patients with contained cervical disk herniation. METHODS: A prospective
randomized clinical trial was conducted including 34 patients with radicular pain
due to a single contained cervical disk herniation who were treated with either
PCN or PRF. Demographic data were collected, and the Medical Outcomes Study 12
Item Short Form (SF-12) Health Survey, visual analog scale (VAS), and the Neck
Disability Index (NDI) were completed 1, 2, and 3 months after treatment.
Treatment satisfaction and complications were recorded. RESULTS: In the PCN group
(n = 17, mean age 52.4 years, 10 female/7 male), patients were treated at C5 to
C6 (8 cases) or C6 to C7 (9 cases). In the PRF group (n = 17, mean age 49.5
years, 8 female/9 male), patients were treated at C3 to C4 (1 case), C5 to C6 (10
cases), or C6 to C7 (6 cases). At 3 months, mean pain VAS improved significantly
from baseline in the PCN group (mean improvement: 43.4 points) and in the PRF
group (34.0 points). However, improvement in 1 group was not superior compared to
the other group (P = 0.48). No serious complications were reported. CONCLUSION:
Within 3 months, both PCN and PRF show significant pain improvement in patients
with contained cervical disk herniation, but none is superior to the other. Both
treatment options appear to be effective and safe in regular clinical practice.
PMID- 27611827
TI - Effects of wearing and removing dentures on oropharyngeal motility during
swallowing.
AB - Wearing dentures and dysphagia are common in older individuals; however, it is
still unknown how dentures affect oral and pharyngeal swallowing. The purpose of
this study was to reveal the effects of wearing and removing dentures on
oropharyngeal movements during pharyngeal swallowing in the feeding sequence of
solid food. Participants were 25 edentulous volunteers (nine men, 16 women; mean
age 76.2 years) who wore complete dentures. The test food was minced agar jelly
containing barium sulphate. Subjects were instructed to feed and swallow the test
food with or without dentures during observation using videofluorography. We
quantitatively evaluated the range, distance and duration of oropharyngeal
movements during pharyngeal swallowing. When dentures were absent, the range of
mandible and hyoid movements were significantly expanded in the anterosuperior
direction, and the range of laryngeal movement was significantly expanded in the
anterior direction. Additionally, the posterior pharyngeal wall contraction and
upper oesophageal sphincter opening significantly increased. In addition, the
distances of the mandible, hyoid and laryngeal movements and the mandibular
duration were significantly extended when dentures were absent. No significant
differences were observed in the duration of movements of other organs between
wearing and removing dentures. The hyoid bone, larynx, posterior pharyngeal wall
and upper oesophageal sphincter do not change their duration of movements when
dentures were removed but, rather, expand their range of movement. This might be
a spatial change of oropharyngeal movement to avoid temporal changes in
pharyngeal swallowing when dentures were absent in edentulous older individuals.
PMID- 27611828
TI - Benzodiazepine use in seizure emergencies: A systematic review.
AB - PURPOSE: The aim of this review was to systematically examine safety and efficacy
outcomes, as well as patient/caregiver satisfaction, from clinical studies in
pediatric and adult patients treated with benzodiazepines (BZDs) through various
administration routes in response to seizure emergencies. METHODS: A literature
search was conducted to identify articles describing the use of various routes of
administration (RoAs) of BZDs for the treatment of seizure emergencies through
April 21, 2015, using EmbaseTM and PubMed(r). Eligible studies included (a)
randomized controlled trials or (b) controlled nonrandomized clinical trials,
either retrospective or prospective. Outcome assessments reviewed were 1) time to
administration, 2) time to seizure termination, 3) rate of treatment failure, 4)
prevention of seizure recurrence, 5) patient and caregiver treatment
satisfaction, 6) adverse events related to BDZ treatment or RoA, and 7)
respiratory adverse events. RESULTS: Seventy-five studies evaluated safety and
efficacy using individual or comparator BDZs of various RoAs for treating seizure
emergencies in all-aged patients with epilepsy. Buccal, intranasal (IN), or
intramuscular (IM) BZDs were often more rapidly administered compared with rectal
and intravenous (IV) formulations. Time to seizure termination, seizure
recurrence rates, and adverse events were generally similar among RoAs, whereas
nonrectal RoAs resulted in greater patient and caregiver satisfaction compared
with rectal RoA. SIGNIFICANCE: Results of this systematic literature review
suggest that nonrectal and non-IV BZD formulations provide equal or improved
efficacy and safety outcomes compared with rectal and IV formulations for the
treatment of seizure emergencies.
PMID- 27611829
TI - Narrow QRS Tachycardia with Varying Intervals: What Is the Mechanism?
PMID- 27611830
TI - Ultra Low Dose CT Pulmonary Angiography with Iterative Reconstruction.
AB - OBJECTIVE: Evaluation of a new iterative reconstruction algorithm (IMR) for
detection/rule-out of pulmonary embolism (PE) in ultra-low dose computed
tomography pulmonary angiography (CTPA). METHODS: Lower dose CT data sets were
simulated based on CTPA examinations of 16 patients with pulmonary embolism (PE)
with dose levels (DL) of 50%, 25%, 12.5%, 6.3% or 3.1% of the original tube
current setting. Original CT data sets and simulated low-dose data sets were
reconstructed with three reconstruction algorithms: the standard reconstruction
algorithm "filtered back projection" (FBP), the first generation iterative
reconstruction algorithm iDose and the next generation iterative reconstruction
algorithm "Iterative Model Reconstruction" (IMR). In total, 288 CTPA data sets
(16 patients, 6 tube current levels, 3 different algorithms) were evaluated by
two blinded radiologists regarding image quality, diagnostic confidence,
detectability of PE and contrast-to-noise ratio (CNR). RESULTS: iDose and IMR
showed better detectability of PE than FBP. With IMR, sensitivity for detection
of PE was 100% down to a dose level of 12.5%. iDose and IMR showed superiority to
FBP regarding all characteristics of subjective (diagnostic confidence in
detection of PE, image quality, image noise, artefacts) and objective image
quality. The minimum DL providing acceptable diagnostic performance was 12.5% (=
0.45 mSv) for IMR, 25% (= 0.89 mSv) for iDose and 100% (= 3.57 mSv) for FBP. CNR
was significantly (p < 0.001) improved by IMR compared to FBP and iDose at all
dose levels. CONCLUSION: By using IMR for detection of PE, dose reduction for
CTPA of up to 75% is possible while maintaining full diagnostic confidence. This
would result in a mean effective dose of approximately 0.9 mSv for CTPA.
PMID- 27611831
TI - Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis.
AB - Obesity is a risk factor for osteoarthritis (OA). To investigate the roles of
increased mechanical loading in the onset of obesity-induced OA, knee joints were
histologically analyzed after applying a tail suspension (TS) model to a high-fat
diet (HFD)-induced OA model. Mice were divided into four groups: normal diet (ND)
with normal loading (NL) group; HFD with NL group; ND with TS group; and HFD with
TS group. Whole knee joints were evaluated by immunohistological analysis. The
infrapatellar fat pad (IPFP) was excised and mRNA expression profiles were
compared by qPCR analysis. After twelve weeks of the diet, body weight was
increased by HFD in both the NL group and TS group. Upon histological analysis,
the irregularity of the surface layer of articular cartilage was observed only in
the NL+HFD group. Osteophyte area increased as a result of HFD in both the NL and
TS groups, although osteophyte area in the TS+HFD group was smaller than that of
the NL+HFD group. In the evaluation of the IPFP by qPCR, adipokines and
inflammatory cytokines also increased as a result of HFD. While TGF-beta
increased as a result of HFD, the trend was slightly lower in the TS group, in
parallel with osteophyte area. To detect apoptosis of articular chondrocytes,
TUNEL staining was employed. TUNEL-positive cells were abundantly observed in the
articular cartilage in the HFD mice regardless of mechanical loading. IPFP
inflammation, enhanced chondrocyte apoptosis, and osteophyte formation were seen
even in the TS group as a result of a HFD. In all, these data demonstrate that
HFD contributed to osteophyte formation through mechanical loading dependent and
independent mechanisms.
PMID- 27611832
TI - The Role of the Rho/ROCK Pathway in Ang II and TGF-beta1-Induced Atrial
Remodeling.
AB - OBJECTIVES: To study the role of the Rho/ROCK pathway in Ang II and TGF-beta1
induced atrial remodeling. METHODS AND RESULTS: A canine atrial fibrillation (AF)
model was established by rapid atrial pacing (RAP) of the left atrium. The roles
of TGF-beta1, the RhoA/ROCK signaling pathway and connective tissue growth factor
(CTGF) in atrial remodeling were studied via both in vitro and in vivo
experiments. Each of the dogs that received RAP developed persistent AF within 4
weeks. The mRNA expression levels of TGF-beta1 (1.32+/-0.38), Collagen-I(1.33+/
0.91), CTGF(5.83+/-3.71), RhoA(1.23+/-0.57) and ROCK-1 (1.02+/-0.27) in the left
atrium were significantly increased following 4 weeks of RAP. Angiotensin II (Ang
II) induced the proliferation of atrial fibroblasts and up-regulated the
expression of both CTGF and ROCK-1 in a dose-dependent manner. Simvastatin and
Y27632 reversed Ang II-induced CFs proliferation, as well as ROCK-1(0.89+/-0.05
and 1.27+/-0.03, respectively) and CTGF (0.87+/-0.04 and 0.91+/-0.02,
respectively) expression. The expression mRNA of ROCK-1(1.74+/-0.13) and CTGF
(2.28+/-0.11) can upregulated by TGF-beta1, and down-regulated by Simvastatin
(1.22+/-0.03 vs 2.27+/-0.11), Y27632 (1.01+/-0.04 vs 1.64+/-0.03), Los (1.04+/
0.11 vs 1.26+/-0.05), respectively. Losartan and Simvastatin attenuated the
effects of TGF-beta1, inhibited RhoA activity as opposed to RhoA protein
expression. Y27632 had no effect on either the expression or the activity of
RhoA. CONCLUSIONS: The increased expression of profibrotic factors (CTGF, ROCK1
and Smad2/3) played an important role in our RAP-induced AF model. Increased
atrial profibrotic factors involve the activation of either the TGF
beta1/RhoA/ROCK-1 or the TGF-beta1/Smad2/3 signaling pathway.
PMID- 27611833
TI - Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided,
Intensity Modulated Radiotherapy (IG-IMRT) or IG-IMRT Alone for Locally Advanced
Non-Small Cell Lung Cancer.
AB - BACKGROUND: Image-guided (IG) intensity-modulated radiotherapy (IMRT) enables
maximal tumor margin reduction for the sparing of organs at risk (OARs) when used
to treat locally advanced non-small cell lung cancer (NSCLC) with definitive
chemo-radiation. It also allows for the incorporation of stereotactic ablative
radiotherapy (SABR) into the treatment regimen. Here, we describe our initial
experience in combining definitive upfront SABR to the primary lesion with chemo
radiation delivered with conventionally fractionated IG-IMRT to the remaining
regional disease; along with clinical outcome following chemo-radiation with
conventionally fractionated IG-IMRT alone in the treatment of locally advanced
NSCLC. METHODS: The clinical outcome of 29 patients with locally advanced NSCLC
who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR
followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both)
was retrospectively reviewed. RESULTS: After a median follow up of 23.7 months,
the median overall survival (OS) and progression-free survival (PFS) were 19.8
and 11.3 months, respectively. The 2 year local, regional, and distant control
was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients
following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT
alone. SABR + IG-IMRT was well tolerated. No >= grade 3 radiation-related
toxicity was observed. CONCLUSION: Definitive upfront SABR followed by IG-IMRT in
selected patients with locally advanced NSCLC warrants further investigation in
future clinical trials, while chemo-radiation with IG-IMRT alone was well
tolerated.
PMID- 27611834
TI - Discovery of Enzymatic Targets of Transcriptional Activators via in Vivo Covalent
Chemical Capture.
AB - The network of activator protein-protein interactions (PPIs) that underpin
transcription initiation is poorly defined, particularly in the cellular context.
The transient nature of these contacts and the often low abundance of the
participants present significant experimental hurdles. Through the coupling of in
vivo covalent chemical capture and shotgun LC-MS/MS (MuDPIT) analysis, we can
trap the PPIs of transcriptional activators in a cellular setting and identify
the binding partners in an unbiased fashion. Using this approach, we discover
that the prototypical activators Gal4 and VP16 target the Snf1 (AMPK) kinase
complex via direct interactions with both the core enzymatic subunit Snf1 and the
exchangeable subunit Gal83. Further, we use a tandem reversible formaldehyde and
irreversible covalent chemical capture approach (TRIC) to capture the Gal4-Snf1
interaction at the Gal1 promoter in live yeast. Together, these data support a
critical role for activator PPIs in both the recruitment and positioning of
important enzymatic complexes at a gene promoter and represent a technical
advancement in the discovery of new cellular binding targets of transcriptional
activators.
PMID- 27611836
TI - Assessment of light stability of drugs in blood and plasma.
AB - AIM: A procedure was developed for the assessment of photochemical stability of
drugs in blood and plasma under standardized conditions. The procedure avoids a
variable outcome of photochemical stability experiments and tests relevant worst
case conditions so that unnecessary light protection is avoided.
Results/methodology: Blood and plasma were spiked with a mixture of drugs and
incubated in a Suntest CPS(+), in the laboratory on the bench and near the window
on a sunny summer day. The results were compared. DISCUSSION/CONCLUSION: No
protection from light, limited protection from light and full protection from
light are advised for drugs that are stable in plasma in the Suntest CPS(+) at
250 W/m(2) for at least 30 min, for 5-30 min and for <5 min, respectively.
PMID- 27611837
TI - Gender differences in posttraumatic stress symptoms and the level of
posttraumatic growth among a Polish sample of HIV-positive individuals.
AB - The main goal of the current study was to investigate gender differences in the
relationship between the level of posttraumatic stress symptoms (PTSSs) and the
intensity of posttraumatic growth (PTG), treated as the explained variable, among
a Polish sample of HIV-positive individuals (n = 250) while controlling for
participants' ages and time since HIV diagnosis. The level of PTG was measured
using the Polish adaptation of the Posttraumatic Growth Inventory. The level of
PTSSs was assessed using the PTSD Factorial Version Inventory. HIV-positive women
scored higher for some PTSSs (intrusion/arousal) and for a particular PTG
dimension (spiritual change). In addition, the PTSSs that occurred were
negatively related to the PTG level but only among HIV-positive women. Given the
important health-related benefits associated with PTG among HIV-positive people,
it is vital to shape competencies for effective growth promotion among these
individuals, taking into account gender differences within this phenomenon.
PMID- 27611838
TI - Asymmetric Polymer Particles with Anisotropic Curvatures by Annealing Polystyrene
Microspheres on Poly(vinyl alcohol) Films.
AB - Anisotropic polymer particles such as Janus particles have attracted significant
attention in recent years because of their unique properties and unusual self
assembly behavior. Most anisotropic polymer particles synthesized so far,
however, only have different chemical regions compartmentalized on the particles.
It remains a great challenge to fabricate anisotropic polymer particles with
different shapes within a single particle. A novel approach is developed to
prepare anisotropic polymer particles that contain two hemispheres with different
curvatures by annealing polystyrene microspheres on poly(vinyl alcohol) films.
During the annealing process, the polymer microspheres gradually sink into the
polymer films and transform to asymmetric polymer particles, driven by the
surface and interfacial tensions of the polymers. Selective removal techniques
are also used to confirm the morphologies of the asymmetric particles.
PMID- 27611835
TI - Down syndrome as risk factor for respiratory syncytial virus hospitalization: A
prospective multicenter epidemiological study.
AB - BACKGROUND: Respiratory syncytial virus (RSV) infection in childhood,
particularly in premature infants, is associated with significant morbidity and
mortality. OBJECTIVES: To compare the hospitalization rates due to RSV infection
and severity of disease between infants with and without Down syndrome (DS) born
at term and without other associated risk factors for severe RSV infection.
PATIENTS/METHODS: In a prospective multicentre epidemiological study, 93 infants
were included in the DS cohort and 68 matched by sex and data of birth (+/-1
week) and were followed up to 1 year of age and during a complete RSV season.
RESULTS: The hospitalization rate for all acute respiratory infection was
significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%,
P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH
cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was
recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to
presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively.
CONCLUSIONS: Infants with DS showed a higher rate of hospitalization due to acute
lower respiratory tract infection and RSV infection compared to non-DS infants.
Including DS infants in recommendations for immunoprophylaxis of RSV disease
should be considered.
PMID- 27611839
TI - Stream network geomorphology mediates predicted vulnerability of anadromous fish
habitat to hydrologic change in southeast Alaska.
AB - In rivers supporting Pacific salmon in southeast Alaska, USA, regional trends
toward a warmer, wetter climate are predicted to increase mid- and late-21st
century mean annual flood size by 17% and 28%, respectively. Increased flood size
could alter stream habitats used by Pacific salmon for reproduction, with
negative consequences for the substantial economic, cultural, and ecosystem
services these fish provide. We combined field measurements and model simulations
to estimate the potential influence of future flood disturbance on geomorphic
processes controlling the quality and extent of coho, chum, and pink salmon
spawning habitat in over 800 southeast Alaska watersheds. Spawning habitat
responses varied widely across watersheds and among salmon species. Little
variation among watersheds in potential spawning habitat change was explained by
predicted increases in mean annual flood size. Watershed response diversity was
mediated primarily by topographic controls on stream channel confinement, reach
scale geomorphic associations with spawning habitat preferences, and complexity
in the pace and mode of geomorphic channel responses to altered flood size.
Potential spawning habitat loss was highest for coho salmon, which spawn over a
wide range of geomorphic settings, including steeper, confined stream reaches
that are more susceptible to streambed scour during high flows. We estimated that
9-10% and 13-16% of the spawning habitat for coho salmon could be lost by the
2040s and 2080s, respectively, with losses occurring primarily in confined,
higher-gradient streams that provide only moderate-quality habitat. Estimated
effects were lower for pink and chum salmon, which primarily spawn in unconfined
floodplain streams. Our results illustrate the importance of accounting for
valley and reach-scale geomorphic features in watershed assessments of climate
vulnerability, especially in topographically complex regions. Failure to consider
the geomorphic context of stream networks will hamper efforts to understand and
mitigate the vulnerability of anadromous fish habitat to climate-induced
hydrologic change.
PMID- 27611842
TI - WITHDRAWN: Neonatal Screening for congenital hypothyroidism in Razavi Khorasan
Province, Iran.
AB - is withdrawn from publication by Editors of the journal due to ethical issue and
authorship issues (conflict of interest) - the request by authors to change the
order in the list of authors and to add new authors after acceptance of the
article for publication and publication ahead of print on website of the journal
without reasonable explanation and statement of authorship.
PMID- 27611840
TI - In Vivo Imaging Demonstrates That Borrelia burgdorferi ospC Is Uniquely Expressed
Temporally and Spatially throughout Experimental Infection.
AB - Borrelia burgdorferi is a spirochetal bacterium transmitted by the Ixodes tick
that causes Lyme disease in humans due to its ability to evade the host immune
response and disseminate to multiple immunoprotective tissues. The pathogen
undergoes dynamic genetic alterations important for adaptation from the tick
vector to the mammalian host, but little is known regarding the changes at the
transcriptional level within the distal tissues they colonize. In this study, B.
burgdorferi infection and gene expression of the essential virulence determinant
ospC was quantitatively monitored in a spatial and temporal manner utilizing
reporter bioluminescent borrelial strains with in vivo and ex vivo imaging.
Although expressed from a shuttle vector, the PospC-luc construct exhibited a
similar expression pattern relative to native ospC. Bacterial burden in skin,
inguinal lymph node, heart, bladder and tibiotarsal joint varied between tissues
and fluctuated over the course of infection possibly in response to unique cues
of each microenvironment. Expression of ospC, when normalized for changes in
bacterial load, presented unique profiles in murine tissues at different time
points. The inguinal lymph node was infected with a significant B. burgdorferi
burden, but showed minimal ospC expression. B. burgdorferi infected skin and
heart induced expression of ospC early during infection while the bladder and
tibiotarsal joint continued to display PospC driven luminescence throughout the
21 day time course. Localized skin borrelial burden increased dramatically in the
first 96 hours following inoculation, which was not paralleled with an increase
in ospC expression, despite the requirement of ospC for dermal colonization.
Quantitation of bioluminescence representing ospC expression in individual
tissues was validated by qRT-PCR of the native ospC transcript. Taken together,
the temporal regulation of ospC expression in distal tissues suggests a role for
this virulence determinant beyond early infection.
PMID- 27611843
TI - Circadian rhythmicity in substance use disorder male patients with and without
comorbid depression under ambulatory and therapeutic community treatment.
AB - Although there have been described alterations of circadian rhythmicity both in
patients with substance use disorder (SUD) and patients with major depressive
disorder (MDD), the circadian characteristics of SUD patients with comorbid MDD
(SUD-MDD) are unknown. Likewise, the possible influence of the different
modalities of treatments (ambulatory or therapeutic community) upon the circadian
rhythmicity of SUD patients has not been characterized. Therefore, this study
analyzes the circadian rhythmic profiles of SUD and SUD-MDD patients under
ambulatory and therapeutic community treatment. The sample was composed of 40 SUD
and 40 SUD-MDD men, aged 22-55 yrs, under treatment and with abstinence for at
least three months (including each group 20 ambulatory and 20 from therapeutic
community). Patients completed a sociodemographic, clinical and sleep-wake
schedules interview, the Composite Scale of Morningness, and wore on the wrist an
ambulatory device known as iButton(r) Thermochron DS1921H, which registered their
distal skin temperature every two minutes for 48 hours. All the groups showed a
tendency to morningness without differences among them in concordance with their
sleep-wake schedules. With regard to distal skin temperature circadian rhythm,
SUD patients showed higher values than SUD-MDD in amplitude, relative amplitude,
percentage rhythm, and first harmonic power, and lower minimum temperature in 10
consecutive hours (p < .043, in all cases). Therapeutic community group values
were lower in minimum temperature and higher in amplitude, relative amplitude,
and 12 harmonic accumulated power (p < .028, in all cases) as compared to
ambulatory ones. Moreover, all groups showed higher Rayleigh vector and rhythm
stability as compared to normative population (p < .043, in both cases). The
circadian rhythmic differences observed for diagnosis and type of treatment are
indicative of a higher circadian rhythmicity robustness in SUD and therapeutic
community patients as compared to SUD-MDD and ambulatory ones, respectively.
Although drug consumption exerts a negative effect on the circadian rhythmicity,
our results (high amplitude and rhythm stability) are indicative of an adequate
circadian functioning as well as of an adjustment to the light-dark cycle in both
diagnosis and type of treatment which may constitute a marker of the adherence to
treatment and recovery status.
PMID- 27611841
TI - Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A
Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides.
AB - In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen
(PSMA) peptides, kidney and/or salivary glands doses limit the activity which can
be administered. The aim of this work was to investigate the effect of the ligand
amount and injected activity on the tumor-to-normal tissue biologically effective
dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a
recently developed physiologically based pharmacokinetic model was adapted for
PSMA targeting peptides. General physiological parameters were taken from the
literature. Individual parameters were fitted to planar gamma camera measurements
(177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on
the estimated parameters, the pharmacokinetics of tumor, salivary glands,
kidneys, total body and red marrow was simulated and time-integrated activity
coefficients were calculated for different peptide amounts. Based on these
simulations, the absorbed doses and BEDs for normal tissue and tumor were
calculated for all activities leading to a maximal tolerable kidney BED of 10
Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal
red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination
> 0.85, acceptable relative standard errors and low parameter correlations. All
estimated parameters were in a physiologically reasonable range. The amounts (for
25-29 nmol) and pertaining activities leading to a maximal tumor dose,
considering the defined maximal tolerable doses to organs of risk, were
calculated to be 272+/-253 nmol (452+/-420 MUg) and 7.3+/-5.1 GBq. Using the
actually injected amount (235+/-155 MUg) and the same maximal tolerable doses,
the potential improvement for the tumor BED was 1-3 fold. The results suggest
that currently given amounts for therapy are in the appropriate order of
magnitude for many lesions. However, for lesions with high binding site density
or lower perfusion, optimizing the peptide amount and activity might improve the
tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.
PMID- 27611844
TI - Experimental Study of the Formation of Organosulfates from alpha-Pinene
Oxidation. Part I: Product Identification, Formation Mechanisms and Effect of
Relative Humidity.
AB - In the present study, quasi-static reactor and atmospheric simulation chamber
experiments were performed to investigate the formation of alpha-pinene-derived
organosulfates. Organosulfates (R-OSO3H) were examined for the reactions between
acidified ammonium sulfate particles exposed to an individual gaseous volatile
organic compound, such as alpha-pinene and oxidized products (alpha-pinene oxide,
isopinocampheol, pinanediol and myrtenal). Molecular structures were elucidated
by liquid chromatography interfaced to high-resolution quadrupole time-of-flight
mass spectrometry equipped with electrospray ionization (LC/ESI-HR-QTOFMS). New
organosulfate products were detected and identified for the first time in the
present study. Reaction with alpha-pinene oxide was found to be a favored pathway
for organosulfate formation (C10H18O5S) and to yield organosulfate dimers
(C20H34O6S and C20H34O9S2) and trimers (C30H50O10S2) under dry conditions (RH <
1%) and high particle acidity and precursor concentrations (1 ppm). The role of
relative humidity on organosulfate formation yields and product distribution was
specifically examined. Organosulfate concentrations were found to decrease with
increasing relative humidity. Mechanistic pathways for organosulfate formation
from the reactions between alpha-pinene, alpha-pinene oxide, isopinocampheol, or
pinanediol with acidified ammonium sulfate particles are proposed.
PMID- 27611846
TI - A self-inducible heterologous protein expression system in Escherichia coli.
AB - Escherichia coli is an important experimental, medical and industrial cell
factory for recombinant protein production. The inducible lac promoter is one of
the most commonly used promoters for heterologous protein expression in E. coli.
Isopropyl-beta-D-thiogalactoside (IPTG) is currently the most efficient molecular
inducer for regulating this promoter's transcriptional activity. However,
limitations have been observed in large-scale and microplate production,
including toxicity, cost and culture monitoring. Here, we report the novel SILEX
(Self-InducibLe Expression) system, which is a convenient, cost-effective
alternative that does not require cell density monitoring or IPTG induction. We
demonstrate the broad utility of the presented self-inducible method for a panel
of diverse proteins produced in large amounts. The SILEX system is compatible
with all classical culture media and growth temperatures and allows protein
expression modulation. Importantly, the SILEX system is proven to be efficient
for protein expression screening on a microplate scale.
PMID- 27611847
TI - Temperature-driven changes in the diet preference of omnivorous copepods: no more
meat when it's hot? A response to Winder et al.
AB - The study of environmental impact on feeding preferences of omnivores is a
rapidly growing field. Here, we show that the criticism put forward in a comment
on our original study is largely unfounded.
PMID- 27611845
TI - Age-Related Sensory Impairments and Risk of Cognitive Impairment.
AB - OBJECTIVES: To evaluate the associations between sensory impairments and 10-year
risk of cognitive impairment. DESIGN: The Epidemiology of Hearing Loss Study
(EHLS), a longitudinal, population-based study of aging in the Beaver Dam,
Wisconsin community. Baseline examinations were conducted in 1993 and follow-up
examinations have been conducted every 5 years. SETTING: General community.
PARTICIPANTS: EHLS members without cognitive impairment at EHLS-2 (1998-2000).
There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data
and follow-up information. MEASUREMENTS: Cognitive impairment was defined as a
Mini-Mental State Examination score of <24 or history of dementia or Alzheimer's
disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5,
1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli
Robson contrast sensitivity of <1.55 log units in the better eye, and olfactory
impairment was a San Diego Odor Identification Test score of <6. RESULTS:
Hearing, visual, and olfactory impairment were independently associated with
cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence
interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR =
3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing
impairment, 81% with visual impairment, and 76% with olfactory impairment did not
develop cognitive impairment during follow-up. CONCLUSION: The relationship
between sensory impairment and cognitive impairment was not unique to one sensory
system, suggesting that sensorineural health may be a marker of brain aging. The
development of a combined sensorineurocognitive measure may be useful in
uncovering mechanisms of healthy brain aging.
PMID- 27611848
TI - Long time response with chemotherapy in ROS1 NSCLC patient with unusual
metastatic site.
AB - During the last decade the therapeutic landscape of Non Small Cell Lung Cancer
(NSCLC) has profoundly changed with the identification of actionable genetic
alterations that defined molecularly selected subgroups of patients with specific
clinic-pathological characteristics and increased sensitivity to specific
targeted agents. The presence of ROS1 rearrangements defines a small subgroup of
lung adenocarcinomas (~1-2%) with peculiar clinic-pathological characteristics
and increased sensitivity to Crizotinib. It has been reported that ROS1
tranlslocated NSCLCs may also respond well to Pemetrexed-based chemotherapy.
Moreover, patients with oncogene-addicted NSCLC may present peculiar pattern of
metastatization and, in some instances, are associated with unusual site of
metastases. Herein, we present a case of a young woman with bilateral ovarian
metastases from a ROS1-positive adenocarcinoma of the lung with a lengthy
progression-free survival on Pemetrexed-containing chemotherapy.
PMID- 27611849
TI - The Prison Economy of Needles and Syringes: What Opportunities Exist for Blood
Borne Virus Risk Reduction When Prices Are so High?
AB - AIM: A formal Needle and Syringe Program (NSP) is not provided in Australian
prisons. Injecting equipment circulates in prisons as part of an informal and
illegal economy. This paper examined how this economy generates blood-borne virus
(BBV) risk and risk mitigation opportunities for inmates. METHOD: The HITS-p
cohort recruited New South Wales inmates who had reported ever injecting drugs
and who had a negative HCV serological test within 12 months prior to enrolment.
For this study, qualitative interviews were conducted with 30 participants
enrolled in HITS-p. Participants included 10 women and were incarcerated in 12
prisons. RESULTS: A needle/syringe was nominated as being typically priced in the
'inside' prison economy at $100-$150, with a range of $50-$350. Purchase or hire
of equipment was paid for in cash (including transactions that occurred outside
prison) and in exchange for drugs and other commodities. A range of other
resources was required to enable successful needle/syringe economies, especially
relationships with visitors and other prisoners, and violence to ensure payment
of debts. Strategies to mitigate BBV risk included retaining one needle/syringe
for personal use while hiring out others, keeping drug use (and ownership of
equipment) "quiet", stealing used equipment from the prison health clinic, and
manufacture of syringes from other items available in the prison. CONCLUSIONS:
The provision of prison NSP would disrupt the inside economies built around
contraband needles/syringes, as well as minimise BBV risk. However, any model of
prison NSP should be interrogated for any unanticipated markets that could be
generated as a result of its regulatory practices.
PMID- 27611850
TI - Modulatory effects of interferon-gamma and interleukin-4 on cellular immune
responses against Hypoderma lineatum antigens.
AB - This study investigates the in vitro modulatory effects of interferon-gamma (IFN
gamma) and interleukin-4 (IL-4) on both proliferative bovine T cell responses and
IL-10 production induced by different antigens [crude larval extract and the
purified fractions hypodermin A, B and C (HyA, HyB, HyC)] obtained from first
instars of Hypoderma lineatum (Diptera: Oestridae), alone or in the presence of
the mitogen concanavalin A. Incubation with the different parasitic antigens
resulted in significant inhibition of T cell proliferation and IL-10 production,
which, in general, did not revert after the addition of IFN-gamma and IL-4. In
the absence of antigens, IL-4 induced significant inhibition of mitogen-induced T
cell responses. Exogenous IFN-gamma exhibited an inhibitory effect on cell
proliferation in the presence of the purified fractions HyB and HyC. These in
vitro data suggest that far from neutralizing the effects of larval antigens, the
addition of IFN-gamma potentiates their anti-proliferative activity; by contrast,
IL-4 had no consistent effects on proliferative responses to Hypoderma. IL-4
provoked an increment of IL-10 levels in supernatants of HyB-stimulated cells. In
conclusion, exogenous IFN-gamma and IL-4 were unable to counteract the suppressor
effects of H. lineatum antigens.
PMID- 27611851
TI - Simulation for training in resource-restricted countries: using a scalable
temporal bone surgical simulator.
PMID- 27611853
TI - Dosimetric Comparison between Three-Dimensional Magnetic Resonance Imaging-Guided
and Conventional Two-Dimensional Point A-Based Intracavitary Brachytherapy
Planning for Cervical Cancer.
AB - OBJECTIVE: The purpose of this study was to comprehensively compare the 3
dimensional (3D) magnetic resonance imaging (MRI)-guided and conventional 2
dimensional (2D) point A-based intracavitary brachytherapy (BT) planning for
cervical cancer with regard to target dose coverage and dosages to adjacent
organs-at risk (OARs). METHODS: A total of 79 patients with cervical cancer were
enrolled to receive 2D point A-based BT planning and then immediately to receive
3D planning between October 2011 and April 2013 at the First Hospital Affiliated
to Xi'an Jiao Tong University (Xi'an, China). The dose-volume histogram (DVH)
parameters for gross tumor volume (GTV), high-risk clinical target volume (HR
CTV), intermediate-risk clinical target volume (IR-CTV) and OARs were compared
between the 2D and 3D planning. RESULTS: In small tumors, there was no
significant difference in most of the DVHs between 2D and 3D planning (all
p>0.05). While in big tumors, 3D BT planning significantly increased the DVHs for
most of the GTV, HR-CTV and IR-CTV, and some OARs compared with 2D planning (all
P<0.05). In 3D planning, DVHs for GTV, HR-CTV, IR-CTV and some OARs were
significantly higher in big tumors than in small tumors (all p<0.05). In
contrast, in 2D planning, DVHs for almost all of the HR-CTV and IR-CTV were
significantly lower in big tumors (all p<0.05). In eccentric tumors, 3D planning
significantly increased dose coverage but decreased dosages to OARs compared with
2D planning (p<0.05). In tumors invading adjacent tissues, the target dose
coverage in 3D planning was generally significantly higher than in 2D planning
(P<0.05); the dosages to the adjacent rectum and bladder were significantly
higher but those to sigmoid colon were lower in 3D planning (all P<0.05).
CONCLUSIONS: 3D MRI image-guided BT planning exhibits advantages over 2D planning
in a complex way, generally showing advantages for the treatment of cervical
cancer except small tumors.
PMID- 27611854
TI - Pseudo-Spectral Damping Reduction Factors for the Himalayan Region Considering
Recorded Ground-Motion Data.
AB - Ground-motion prediction equations that are used to predict acceleration values
are generally developed for a 5% viscous damping ratio. Special structures and
structures that use damping devices may have damping ratios other than the
conventionally used ratio of 5%. Hence, for such structures, the intensity
measures predicted by conventional ground-motion prediction equations need to be
converted to a particular level of damping using a damping reduction factor
(DRF). DRF is the ratio of the spectral ordinate at 5% damping to the ordinate at
a defined level of damping. In this study, the DRF has been defined using the
spectral ordinate of pseudo-spectral acceleration and the effect of factors such
as the duration of ground motion, magnitude, hypocenter distance, site
classification, damping, and period are studied. In this study, an attempt has
also been made to develop an empirical model for the DRF that is specifically
applicable to the Himalayan region in terms of these predictor variables. A
recorded earthquake with 410 horizontal motions was used, with data characterized
by magnitudes ranging from 4 to 7.8 and hypocentral distances up to 520 km. The
damping was varied from 0.5-30% and the period range considered was 0.02 to 10 s.
The proposed model was compared and found to coincide well with models in the
existing literature. The proposed model can be used to compute the DRF at any
specific period, for any given value of predictor variables.
PMID- 27611852
TI - Wilson Disease: Epigenetic effects of choline supplementation on phenotype and
clinical course in a mouse model.
AB - Wilson disease (WD), a genetic disorder affecting copper transport, is
characterized by hepatic and neurological manifestations with variable and often
unpredictable presentation. Global DNA methylation in liver was previously
modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We
therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j
offspring could be modified by maternal methyl supplementation during pregnancy.
In an initial experiment, female tx-j mice or wild type mice were fed control or
choline-supplemented diets 2 weeks prior to mating through embryonic day 17.
Transcriptomic analysis (RNA-seq) on embryonic livers revealed tx-j-specific
differences in genes related to oxidative phosphorylation, mitochondrial
dysfunction, and the neurological disorders Huntington's disease and Alzheimer
disease. Maternal choline supplementation restored the transcript levels of a
subset of genes to wild type levels. In a separate experiment, a group of tx-j
offspring continued to receive choline-supplemented or control diets, with or
without the copper chelator penicillamine (PCA) for 12 weeks until 24 weeks of
age. Combined choline supplementation and PCA treatment of 24-week-old tx-j mice
was associated with increased liver transcript levels of methionine metabolism
and oxidative phosphorylation-related genes. Sex differences in gene expression
within each treatment group were also observed. These results demonstrate that
the transcriptional changes in oxidative phosphorylation and methionine
metabolism genes in WD that originate during fetal life are, in part, prevented
by prenatal maternal choline supplementation, a finding with potential relevance
to preventive treatments of WD.
PMID- 27611855
TI - Study on Interactions between the Major Apple Valsa Canker Pathogen Valsa mali
and Its Biocontrol Agent Saccharothrix yanglingensis Hhs.015 Using RT-qPCR.
AB - The mechanism of biocontrol agent Saccharothrix yanglingensis Hhs.015 action
against Valsa mali, a major apple Valsa canker pathogen, was examined using a
novel, sensitive (minimum detection limit 100 pg/MUL) and reliably RT-qPCR
technique. Prior to lesion formation, total concentration of V. mali in the bark
showed a significant decrease (p<0.05) after 24 h of Hhs.015 treatment. This was
more pronounced at 48 and 96 h post treatment. After lesion formation, levels of
V. mali remained constant at the boundary between infected and uninfected bark
tissues, although the relative expansion rate of the lesion was significantly
reduced (p<0.05). Gene expression levels of endo-polygalacturonase, a marker for
fungal pathogenicity, were sharply reduced while host induced resistance callose
synthase levels increased significantly (p<0.05) at the boundary bark at 9 d
after Hhs.015 treatment. The results showed that biocontrol agent Hhs.015
prevented infection of V. mali by inhibiting pathogen growth, down-regulating
pathogenicity factor expression and inducing a high level of host resistance.
PMID- 27611856
TI - Examining the Psychological Effect of Rape Acknowledgment: The Interaction of
Acknowledgment Status and Ambivalent Sexism.
AB - OBJECTIVE: Although the majority of rape survivors do not label their experiences
as rape (i.e., unacknowledged rape), the literature is mixed in terms of how this
affects survivors' psychological functioning. To elucidate the discrepancies, the
present study examined the interaction between rape acknowledgement and
ambivalent sexism in relation to depression and posttraumatic stress disorder
(PTSD) symptoms. METHOD: The analyzed sample included 128 female rape survivors
who were drawn from a larger college sample of 1,595 participants. The
participants completed measures of sexual assault experiences, ambivalent sexism,
and depression and PTSD symptoms. RESULTS: The results supported a significant
interaction between acknowledgement status and benevolent sexism in relation to
both depression and PTSD symptoms. Conversely, the present study failed to find
support for an interaction between acknowledgment status and hostile sexism.
CONCLUSION: The clinical implications suggest that rather than seeing
acknowledging rape as essential to the recovery process, clinicians should assess
for and take into account other factors that may contribute to psychological
functioning. Additionally, the findings support that more complex models of
trauma recovery should be investigated with the goal of working toward a more
comprehensive understanding of the longitudinal process of rape acknowledgment.
PMID- 27611857
TI - Diffuse T2 Signal Hyperintensity of the Teres Minor in a Patient With
Polyarteritis Nodosa.
PMID- 27611859
TI - Dysfunctional organization of default mode network before memory impairments in
type 2 diabetes.
AB - AIMS: Episodic memory depends on the maintenance of an intact default mode
network (DMN), and is one of the earliest cognitive domains to become impaired in
type 2 diabetes mellitus (T2DM). Therefore, exploring the alterations in task
related DMN deactivation and functional connectivity that affect episodic memory
in T2DM will help to enhance our understanding of the allocation patterns
underlying memory function in T2DM. METHODS: The current study assessed changes
in DMN activation and architecture during the encoding of a functional magnetic
resonance imaging task in 39 patients with T2DM and 41 healthy controls which
were recruited from local communities in Beijing, China. RESULTS: We found that
patients with T2DM and intact episodic memory performance exhibited reduced
deactivation in the right precuneus and the middle temporal gyrus during the
episodic memory task. Furthermore, an anterior-posterior disconnection phenotype
and altered topological configuration of the DMN were observed in patients with
T2DM using graph-theoretical approaches. Correlation analysis showed that altered
deactivation during the episodic memory task was closely related to connectivity
dysfunction and topological properties in the DMN. CONCLUSIONS: Our findings
demonstrate that the maintenance of memory in patients with T2DM involves reduced
deactivation and impaired anterior-posterior connections in the DMN during
encoding.
PMID- 27611860
TI - Multicomponent Coupling Reaction of Perfluoroarenes with 1,3-Butadiene and Aryl
Grignard Reagents Promoted by an Anionic Ni(II) Complex.
AB - An anionic Ni complex was isolated and its structure determined by X-ray
crystallography. With such an anionic complex as a key intermediate, a regio- and
stereoselective multicomponent coupling reaction of perfluoroarenes, aryl
Grignard reagents, and 1,3-butadiene in a 1:1:2 ratio was achieved, resulting in
the formation of 1,6-octadiene derivatives containing two aryl groups, one from
the perfluoroarene and the other from the aryl Grignard reagent, at the 3- and 8
positions, respectively.
PMID- 27611858
TI - Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc
Alpha2-Glycoprotein Levels in Patients with Type 2 Diabetes.
AB - ZAG has recently been characterized as a potent metabolic regulator, but the
effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to
study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162
subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA
therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight,
FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C
was significantly increased. Importantly, circulating ZAG and ADI levels in these
patients were also significantly increased after DAPA therapy. Basal ZAG levels
were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post
treatment, whereas basal ADI levels were associated with changes in FAT%, TC,
HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression
and secretion in HepG2 cells. When combined with a PPAR-gammainhibitor GW9662,
the effect of DAPA on ZAG was abrogated. These findings suggest that circulating
ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of
ZAG in the liver via the activation of PPAR-gamma. The changes in ZAG induced by
DAPA may play a physiologic role in enhancing insulin sensitivity.
PMID- 27611861
TI - A urotensin II receptor antagonist, KR36676, decreases vascular remodeling and
inflammation in experimental pulmonary hypertension.
AB - The pathophysiological implications of binding of urotensin II (U-II) to
urotensin II receptor (UT) in pulmonary arterial hypertension (PAH) have been
proposed recently. Besides high expression of U-II in experimental models and
patients with PAH, U-II has been shown to increase proliferation of pulmonary
vascular smooth muscle cells and inflammatory responses, which were critical for
PAH pathophysiology. However, the direct role of the urotensinergic system in the
pathogenesis of PAH is yet to be understood. The aim of the present study was to
determine whether a novel UT antagonist, KR36676, attenuates the
pathophysiological progression of PAH in an animal model of PAH. PAH was induced
by a single subcutaneous injection of monocrotaline (MCT, 60mg/kg) in rats. All
the animals received KR36676 (30mg/kg/day) or vehicle by oral gavage. Three weeks
after MCT-injection, changes in hemodynamic parameters, extent of right
ventricular hypertrophy, fibrosis and pulmonary vascular remodeling, and degree
of protein expression were determined. Oral administration of KR36676 effectively
decreased the MCT-induced increase in right ventricular systolic pressure,
hypertrophy and fibrosis. Furthermore, wall thickness of pulmonary arterioles,
proliferation of pulmonary vascular cells, and inflammatory response
significantly decreased in the KR36676-treated group following MCT injection
compared to that in the MCT-treated vehicle group. These preventive effects of
KR36676 are mediated, at least in part, by suppression of ERK1/2 and NF-kappaB
signaling pathways. The novel UT antagonist, KR36676, effectively prevented MCT
induced PAH progression and pulmonary vascular remodeling in rat model. Our
findings support the therapeutic efficacy of UT antagonist in PAH prevention and
elucidate the possible underlying mechanisms of action.
PMID- 27611862
TI - IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration
via AKT/NF-kappaB pathway.
AB - IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor
progression. Elevated IL-7 expression has been reported to be observed in
prostate cancer tissues and closely associated with poor prognosis. However, the
biological functions of IL-7 and its receptor in prostate cancer cell
invasiveness remain unclear. In our study, we found that the expressions of IL-7
and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently
promoted the invasion and migration of prostate cancer cells, whereas knockdown
of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the
activation of AKT and NF-kappaB, whereas blocking of AKT suppressed IL-7-mediated
NF-kappaB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7
expression of prostate cancer cells, whereas inhibition of NF-kappaB as well as
MMPs activity suppressed IL-7-mediated cell invasion and migration. Together,
these data identify IL-7/IL-7R axis to be involved in prostate cancer cell
invasion and migration, probably via activating AKT/NF-kappaB pathway and
upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may
provide a potential therapeutic strategy to treat prostate cancer.
PMID- 27611864
TI - Determining the optimal developmental stages of Xenopus laevis for initiating
exposures to chemicals for sensitively detecting their feminizing effects on
gonadal differentiation.
AB - Xenopus laevis is an important model for detecting feminizing effects of
endocrine disrupting chemicals (EDCs) on amphibians because its genetic males can
be induced to phenotypic females by estrogenic chemicals. It is crucial that
chemical exposures begin at sensitive developmental stages for gonadal sex
reversal in X. laevis. To determine the optimal stages for initiating exposures,
we investigated gonadal sex-reversal induced by low concentrations of 17alpha
ethinylestradiol (EE2) when exposures were initiated at different stages (3/4,
45/46, 48 and 50) until stage 58. We found that 0.1nM EE2 resulted in 85%, 86%,
43%, and 19% intersex, whereas 1nM EE2 caused 77%, 81%, 17%, and 8% phenotypic
females, when genetic male tadpoles were exposed from stages 3/4, 45/46, 48 and
50, respectively. The data show the sensitivity of X. laevis gonads to EE2 at
stages 45/46 is similar with that at stages 3/4, but the sensitivity decreases at
stage 48 and stage 50, displaying a developmental stage-dependent manner. In
another experiment using the offspring of another pair of frogs, we confirmed
high sensitivity of X. laevis gonads at stages 45/46 to low concentrations of
EE2. Considering that stages 45/46 tadpoles are easier to manipulate and have
higher survival rates than earlier embryos, we propose that stages 45/46 are the
optimal stages for initiating exposure for detecting feminizing effects of EDCs
on gonadal differentiation in X. laevis. The developmental stages for initiating
exposures we determined will guarantee the high sensitivity for detecting
feminizing effects of EDCs with low estrogenic activities on gonadal
differentiation in X. laevis. Also, our study suggests that gonadal
differentiation in X. laevis possibly begins at stages 45/46, but not at later
stages.
PMID- 27611863
TI - Hsp70 May Be a Molecular Regulator of Schistosome Host Invasion.
AB - Schistosomiasis is a debilitating disease that affects over 240 million people
worldwide and is considered the most important neglected tropical disease
following malaria. Free-swimming freshwater cercariae, one of the six
morphologically distinct schistosome life stages, infect humans by directly
penetrating through the skin. Cercariae identify and seek the host by sensing
chemicals released from human skin. When they reach the host, they burrow into
the skin with the help of proteases and other contents released from their
acetabular glands and transform into schistosomula, the subsequent larval worm
stage upon skin infection. Relative to host invasion, studies have primarily
focused on the nature of the acetabular gland secretions, immune response of the
host upon exposure to cercariae, and cercaria-schistosomulum transformation
methods. However, the molecular signaling pathways involved from host-seeking
through the decision to penetrate skin are not well understood. We recently
observed that heat shock factor 1 (Hsf1) is localized to the acetabular glands of
infectious schistosome cercariae, prompting us to investigate a potential role
for heat shock proteins (HSPs) in cercarial invasion. In this study, we report
that cercarial invasion behavior, similar to the behavior of cercariae exposed to
human skin lipid, is regulated through an Hsp70-dependent process, which we show
by using chemical agents that target Hsp70. The observation that biologically
active protein activity modulators can elicit a direct and clear behavioral
change in parasitic schistosome larvae is itself interesting and has not been
previously observed. This finding suggests a novel role for Hsp70 to act as a
switch in the cercaria-schistosomulum transformation, and it allows us to begin
elucidating the pathways associated with cercarial host invasion. In addition,
because the Hsp70 protein and its structure/function is highly conserved, the
model that Hsp70 acts as a behavior transitional switch could be relevant to
other parasites that also undergo an invasion process and can apply more broadly
to other organisms during morphological transitions. Finally, it points to a new
function for HSPs in parasite/host interactions.
PMID- 27611866
TI - Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual
Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on
Pathologically Proven Cases.
AB - OBJECTIVE: To differentiate smoking-related interstitial fibrosis (SRIF) from
usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary
fibrosis and emphysema (CPFE) patients. MATERIALS AND METHODS: This study was
approved by the institutional review board and informed consent was waived. We
included 65 patients who underwent lung biopsy under the suspicion of UIP pattern
on HRCT, and after radiologic-pathologic correlation, they were divided into
three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and
SRIF (n = 9). The quantitative extent of emphysema in the entire lung was
visually assessed and fibrotic patterns were qualitatively analyzed based on six
characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the
honeycombing area, absence of ground grass attenuation/reticulation in
honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the
upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic
regression with a receiver operating characteristic curve was used to predict the
possibility of SRIF. RESULTS: In qualitative analysis of fibrotic patterns, SRIF
tended to exhibit more than three of six fibrotic features, whereas UIP with
emphysema demonstrated about two of these characteristics (p = 0.035). In
addition, SRIF had a higher extent of emphysema than UIP with emphysema when they
have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival
rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035).
CONCLUSION: Fibrotic CT patterns and survival rate differed between SRIF and UIP
with emphysema among CPFE patients, which explains the variable prognosis of
CPFE.
PMID- 27611865
TI - Molecular mechanisms of selenium-Induced spinal deformities in fish.
AB - Selenium toxicity to oviparous vertebrates is often attributed to
selenomethionine (SeMet), which can biomagnify through maternal transfer.
Although oxidative stress is implicated in SeMet toxicity, knowledge gaps remain
in how SeMet causes characteristic spinal deformities. In the present study, we
use the Japanese medaka (Oryzias latipes) model to investigate the role of
oxidative stress, cell death, and the unfolded protein response (UPR) on skeletal
gene expression and SeMet toxicity, linking localization of cellular effects to
observed abnormalities. Medaka embryos were treated with 2.5MUM or 5MUM SeMet for
24h at stage 25 (48h post fertilization). Post treatment, embryos were separated
into normal, deformed (mild, moderate or severe), or dead categories.
Dichlorofluorescein staining demonstrated oxidative stress in tails of embryos
with observable spinal malformations. Furthermore, acridine orange staining for
apoptosis identified significantly more dead cells in tails of treated embryos.
Gene expression studies for the UPR suggest a potential role for CHOP (c/ebp
homologous protein) induced apoptosis deformed embryos after 5MUM SeMet,
accompanied by a significant decrease in PDIA4 (protein disulfide isomerase A4)
and no change in Dnajb9 (ER DNA J Domain-Containing Protein 4). This expression
was distinct from the UPR induced by well-studied ER stress inducer, tunicamycin,
which robustly activated CHOP, PDIA4 and Dnajb9. Finally, SeMet treatment
significantly decreased transcripts of cartilage development, Sox9 (SRY box 9),
while increasing Runx2 in deformed embryos, without altering Twist or Collagen
2a1. Results suggest that oxidative stress, the UPR and cell death play key roles
in SeMet induced deformities and altered skeletal development factors.
PMID- 27611867
TI - The Expression Pattern of the Pre-B Cell Receptor Components Correlates with
Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.
AB - Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at
the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor
for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL
are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR
expression. However, the cellular stage at which BCP-ALL are arrested and whether
this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is
still unclear. Here, we show differential protein expression and copy number
variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL.
Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3
PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the
pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1,
and are arrested at the pro-B stage. Irrespective of subtype, ALL with high
levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate
with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings
suggest that BCP-ALL are arrested at different cellular stages, which relates to
the expression pattern of the pre-BCR components that could serve as prognostic
markers for high-risk pediatric BCP-ALL patients.
PMID- 27611868
TI - Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells.
AB - As part of an international effort to develop vaccines for Theileria lestoquardi,
we undertook a limited screen to test T. lestoquardi orthologues of antigens
recognised by CD8+ T lymphocyte responses against T. annulata and T. parva in
cattle. Five MHC defined sheep were immunized by live T. lestoquardi infection
and their CD8+ T lymphocyte responses determined. Thirteen T. lestoquardi
orthologues of T. parva and T. annulata genes, previously shown to be targets of
CD8+ T lymphocyte responses of immune cattle, were expressed in autologous
fibroblasts and screened for T cell recognition using an IFNgamma assay. Genes
encoding T. lestoquardi antigens Tl8 (putative cysteine proteinase, 349 aa) or
Tl9 (hypothetical secreted protein, 293 aa) were recognise by T cells from one
animal that displayed a unique MHC class I genotype. Antigenic 9-mer peptide
epitopes of Tl8 and Tl9 were identified through peptide scans using CD8+ T cells
from the responding animal. These experiments identify the first T. lestoquardi
antigens recognised by CD8+ T cell responses linked to specific MHC class I
alleles.
PMID- 27611869
TI - Graphitic Carbon Nitride Materials: Sensing, Imaging and Therapy.
AB - Graphitic carbon nitrides (g-C3 N4 ) are a class of 2D polymeric materials mainly
composed of carbon and nitrogen atoms. g-C3 N4 are attracting dramatically
increasing interest in the areas of sensing, imaging, and therapy, due to their
unique optical and electronic properties. Here, the luminescent properties
(mainly includes photoluminescence and electrochemiluminescence), and catalytic
and photoelectronic properties related to sensing and therapy applications of g
C3 N4 materials are reviewed. Furthermore, the fabrication and advantages of
sensing, imaging and therapy systems based on g-C3 N4 materials are summarized.
Finally, the future perspectives for developing the sensing, imaging and therapy
applications of the g-C3 N4 materials are discussed.
PMID- 27611870
TI - Risk assessment and predator learning in a changing world: understanding the
impacts of coral reef degradation.
AB - Habitat degradation is among the top drivers of the loss of global biodiversity.
This problem is particularly acute in coral reef system. Here we investigated
whether coral degradation influences predator risk assessment and learning for
damselfish. When in a live coral environment, Ambon damselfish were able to learn
the identity of an unknown predator upon exposure to damselfish alarm cues
combined with predator odour and were able to socially transmit this learned
recognition to naive conspecifics. However, in the presence of dead coral water,
damselfish failed to learn to recognize the predator through alarm cue
conditioning and hence could not transmit the information socially. Unlike alarm
cues of Ambon damselfish that appear to be rendered unusable in degraded coral
habitats, alarm cues of Nagasaki damselfish remain viable in this same
environment. Nagasaki damselfish were able to learn predators through
conditioning with alarm cues in degraded habitats and subsequently transmit the
information socially to Ambon damselfish. Predator-prey dynamics may be
profoundly affected as habitat degradation proceeds; the success of one species
that appears to have compromised predation assessment and learning, may find
itself reliant on other species that are seemingly unaffected by the same degree
of habitat degradation.
PMID- 27611871
TI - Mannanase Man23 mutant library construction based on a novel cell-free protein
expression system.
AB - BACKGROUND: Mannanases are important enzymes which are widely used as a tool in
agriculture and food industries. To improve the performance of mannanase Man23, a
mutant library was created with rational design, and mutations were introduced on
loops around the catalytic region. The Brevibacillus brevis B16 cell-free system
which was created in this experiment provided the ability to express the mutant
library efficiently. The activities of mutants were measured with a multi-volume
spectrophotometer. RESULTS: The mutant Man1606 gained from this system is a
sextet which has mutations of N146G, S147H, S156P, T157Y, Q206S and T249H
simultaneously on loops 6, 8 and 10. Man1606 showed higher activity and stability
than Man23. The optimal temperature of Man1606 rose by 5 degrees C (from 55 to
60 degrees C) and the optimal pH increased slightly but its range became
broader. CONCLUSION: This experiment demonstrated the B. brevis cell-free system
shortens the expression time and is an efficient tool for mannanase engineering.
(c) 2016 Society of Chemical Industry.
PMID- 27611872
TI - Technoeconomic Assessment of an Advanced Aqueous Ammonia-Based Postcombustion
Capture Process Integrated with a 650-MW Coal-Fired Power Station.
AB - Using a rigorous, rate-based model and a validated economic model, we
investigated the technoeconomic performance of an aqueous NH3-based CO2 capture
process integrated with a 650-MW coal-fired power station. First, the baseline
NH3 process was explored with the process design of simultaneous capture of CO2
and SO2 to replace the conventional FGD unit. This reduced capital investment of
the power station by US$425/kW (a 13.1% reduction). Integration of this NH3
baseline process with the power station takes the CO2-avoided cost advantage over
the MEA process (US$67.3/tonne vs US$86.4/tonne). We then investigated process
modifications of a two-stage absorption, rich-split configuration and
interheating stripping to further advance the NH3 process. The modified process
reduced energy consumption by 31.7 MW/h (20.2% reduction) and capital costs by
US$55.4 million (6.7% reduction). As a result, the CO2-avoided cost fell to
$53.2/tonne: a savings of $14.1 and $21.9/tonne CO2 compared with the NH3
baseline and advanced MEA process, respectively. The analysis of energy breakdown
and cost distribution indicates that the technoeconomic performance of the NH3
process still has great potential to be improved.
PMID- 27611873
TI - Ion-Mediated Polymerase Chain Reactions Performed with an Electronically Driven
Microfluidic Device.
AB - The polymerase chain reaction (PCR) is a powerful method for exponentially
amplifying very low amounts of target DNA from genetic, clinical, and forensic
samples. However, the heating and cooling steps in PCR largely hamper the
miniaturization of thermocyclers for on-site detection of pathogens and point-of
care tests. Herein, we devise an ion-mediated PCR (IM-PCR) strategy by exploiting
ion-induced DNA denaturation/renaturation cycles. DNA duplexes are effectively
denatured in alkaline solutions; whereas, the denatured single-stranded DNA
strands readily reform duplexes at neutral pH. By using an integrated microchip
that can programmably control the solution pH simply switching the potential in a
range of several hundred millivolts, we can trigger IM-PCR at a constant
temperature. Analogously to thermal cycling, 30 cycles of pH-induced
denaturation/renaturation were used to amplify protein DNA fragments as confirmed
by DNA sequencing. We anticipate that this portable, low-cost, and scalable IM
PCR holds great promise for widespread biological, clinical, and environmental
applications.
PMID- 27611874
TI - Blue Light Perception by Both Roots and Rhizobia Inhibits Nodule Formation in
Lotus japonicus.
AB - In many legumes, roots that are exposed to light do not form nodules. Here, we
report that blue light inhibits nodulation in Lotus japonicus roots inoculated
with Mesorhizobium loti. Using RNA interference, we suppressed the expression of
the phototropin and cryptochrome genes in L. japonicus hairy roots. Under blue
light, plants transformed with an empty vector did not develop nodules, whereas
plants exhibiting suppressed expression of cry1 and cry2 genes formed nodules. We
also measured rhizobial growth to investigate whether the inhibition of
nodulation could be caused by a reduced population of rhizobia in response to
light. Although red light had no effect on rhizobial growth, blue light had a
strong inhibitory effect. Rhizobial growth under blue light was partially
restored in signature-tagged mutagenesis (STM) strains in which LOV-HK/PAS- and
photolyase-related genes were disrupted. Moreover, when Ljcry1A and Ljcry2B
silenced plants were inoculated with the STM strains, nodulation was additively
increased. Our data show that blue light receptors in both the host plant and the
symbiont have a profound effect on nodule development. The exact mechanism by
which these photomorphogenetic responses function in the symbiosis needs further
study, but they are clearly involved in optimizing legume nodulation.
PMID- 27611876
TI - Additive value of nicorandil on ATP for further inducing hyperemia in patients
with an intermediate coronary artery stenosis.
AB - BACKGROUND: The induction of hyperemia is of importance to precisely assess the
functional significance of coronary artery lesions with fractional flow reserve
(FFR). Adenosine or ATP alone is used widely in this setting; however, little is
known about the additive value of nicorandil, which acts as a nitrate and a K-ATP
channel opener, to induce further hyperemia. PATIENTS AND METHODS: A total of 183
intermediate native coronary artery lesions from 112 patients were prospectively
enrolled into this study. FFR was measured using a coronary pressure wire during
an intravenous ATP infusion alone (150 mcg/kg/min) (FFRATP) and repeated after an
adjunctive intracoronary nicorandil injection (2.0 mg) (FFRATP+Nico). RESULTS:
Physiologic measurements were completed without any severe adverse effects from
ATP and nicorandil in all patients. FFRATP and FFRATP+Nico had a strong linear
correlation (R=0.79, P<0.001). The FFR value became significantly lower with an
adjunctive intracoronary nicorandil injection compared with ATP alone [FFRATP vs.
FFRATP+Nico, 0.87 (interquartile range: 0.81-0.92) vs. 0.85 (0.79-0.90),
P<0.001]. A total of 18 lesions out of 183 (9.8%) were reclassified after a
nicorandil injection (12 from FFR>0.80 to <=0.80 vs. six from FFR<=0.80 to >0.80,
P=0.26). The adjunctive effect of nicorandil was accentuated with each increment
of FFRATP strata (per 0.05 increase, P for trend<0.001), but with minimal effect
around the borderline FFR zone. CONCLUSION: An adjunctive intracoronary
nicorandil injection is safe, but appears to have little effect in inducing
further hyperemia. Therefore, its effect on the clinical scenario is limited.
PMID- 27611877
TI - Pathologically dissimilar acute stent thromboses in a metal allergic patient.
PMID- 27611878
TI - Structural biology in antiviral drug discovery.
AB - Structural biology has emerged during the last thirty years as a powerful tool
for rational drug discovery. Crystal structures of biological targets alone and
in complex with ligands and inhibitors provide essential insights into the
mechanisms of actions of enzymes, their conformational changes upon ligand
binding, the architectures and interactions of binding pockets. Structure-based
methods such as crystallographic fragment screening represent nowadays invaluable
instruments for the identification of new biologically active compounds. In this
context, three-dimensional protein structures have played essential roles for the
understanding of the activity and for the design of novel antiviral agents
against several different viruses. In this review, the evolution in the
resolution of viral structures is analysed, along with the role of crystal
structures in the discovery and optimisation of new antivirals.
PMID- 27611875
TI - Glomerular filtration rate and proteinuria associations with coronary artery
calcium among HIV-infected and HIV-uninfected men in the Multicenter AIDS Cohort
Study.
AB - BACKGROUND: Decreased kidney function and greater albuminuria are associated with
increased incidence and extent of coronary artery calcium (CAC). We investigated
whether the associations between kidney function and urine protein-to-creatinine
ratio (UPCR) with CAC differ by HIV serostatus. METHODS: Using data from the
Multicenter AIDS Cohort Study, a prospective multicenter US study of men who have
sex with men, we carried out a cross-sectional study comprised of 592 HIV
infected (HIV+) and 378 uninfected (HIV-) men who underwent noncontrast computed
tomography to measure CAC. Logistic and linear regression models were used to
determine whether HIV infection modified associations of estimated glomerular
filtration rate and UPCR with the presence and extent of CAC, adjusting for age,
race, and cardiovascular risk factors. RESULTS: Every 10 U decrease in estimated
glomerular filtration rate below 90 ml/min/1.73 m was significantly associated
with 1.3-fold [95% confidence interval (CI): 1.06-1.51] higher odds of CAC
presence and was similar by HIV serostatus (Pinteraction=0.37). Greater UPCR was
associated with more extensive CAC, with a change in log CAC score of 0.32 (95%
CI: 0.10-0.55) per 1% increase in UPCR. There was a strong trend for effect
modification by HIV serostatus for this association [HIV-: 0.75 (95% CI: 0.26
1.25); HIV+: 0.22 (95% CI: -0.03 to 0.47), Pinteraction=0.06]. CONCLUSION:
Greater CAC burden is apparent among individuals with early kidney disease,
irrespective of HIV serostatus. Increased UPCR is associated with a greater
extent of CAC with a trend for differences by HIV serostatus; a clearer
proteinuria/CAC extent relationship was apparent among HIV- patients.
PMID- 27611879
TI - Estimated Cerebrospina Fluid Pressure and the 5-Year Incidence of Primary Open
Angle Glaucoma in a Chinese Population.
AB - PURPOSE: We aim to assess the longitudinal association between baseline estimated
cerebrospinal fluid pressure (CSFP) and 5-year incident primary open angle
glaucoma (POAG) in a population-based sample of Bai Chinese living in rural
China. METHODS: Among the 2133 Bai Chinese aged 50 years or older who had
participated in the baseline examination of the Yunnan Minority Eye Study, 1520
(71.3%) attended the follow-up examination after five years and 1485 were at risk
of developing POAG. Participants underwent comprehensive ophthalmic examinations
at both baseline and follow-up surveys. CSFP in mmHg was estimated as 0.55 * body
mass index (kg/m2) + 0.16 * diastolic blood pressure (mmHg)-0.18 * age (years)
1.91. Glaucoma was defined using the International Society of Geographical and
Epidemiological Ophthalmology Classification criteria. Multivariate logistic
regression models were established to determine the association between baseline
CSFP and incident POAG. RESULTS: After a mean follow-up time of 5 years, 19 new
cases of POAG were detected, with an incidence rate of 1.3% (95% confidence
interval, 0.7-1.9%). In multivariate logistic regression analysis, after
adjusting for age, gender, education, intraocular pressure, central corneal
thickness, hypertension and diabetes, no significant associations, nor any
trends, were evident between baseline estimated CSFP and incident POAG. The
association between estimated CSFP per mmHg increase in baseline and 5-year
incidence of POAG was also non-significant, with adjusted relative risk of 0.96
(P = 0.11) in multivariate analysis. CONCLUSIONS: This longitudinal cohort study
does not support previously observed cross-sectional association between
estimated CSFP and POAG in population-based studies.
PMID- 27611880
TI - Results of a Tailored Approach to Zenker's Diverticulum: A Single VA Experience.
AB - The transoral division of the esophageal-diverticula septum with a linear
stapler, with CO2 laser, or with harmonic scalpel under rigid endoscopy has
revolutionized the surgical management of Zenker's diverticula. Nevertheless, the
open approach still plays a role in select cases. Our goals are to illustrate the
techniques and the results of our tailored approach to the surgical management of
Zenker's diverticula in U.S. veterans.
PMID- 27611882
TI - [Reasons for Emergency Department Visits: Results of a Patient Survey].
AB - OBJECTIVES: The number of patients visiting emergency departments (ED) is
steadily increasing. The cause for this rise in Germany is unclear and less
examined. This study aimed to assess the reasons of walk-in patients to visit EDs
by using a direct survey. METHODS: During a period of 4 weeks, 2 010 walk-in
patients were anonymously surveyed in 2 major Berlin hospitals using a
standardized questionnaire. Descriptive statistics were used for data analysis.
RESULTS: More than 90% of patients assessed themselves as an emergency and three
quarters of patients reported pain. The majority of patients (57%) tried to
contact statutory health insurance (SHI) office-based physicians in advance and
59% of patients said they would make use of ambulatory emergency facilities if
they were available and well established. However, 55% of patients were unaware
of the emergency service of the association of SHI physicians. CONCLUSION: The
results indicate that centralized ambulatory emergency facilities should be
available 24/7 at hospitals with EDs. Therefore, future planning of emergency
services should integrate providers of ambulatory and inpatient sector.
International experience suggests that different instruments aiming at better
coordination of care, such as integrated call centers, extended ambulatory
services and facilities for less urgent cases located in or nearby hospitals with
EDs should also be implemented in Germany.
PMID- 27611881
TI - Effects of graded levels of liquid brewer's yeast on chemical composition and
fermentation quality in cassava pulp and rice straw-based total mixed ration
silage.
AB - This study aimed to evaluate the effect of liquid brewer's yeast (LBY) addition
on chemical composition and fermentation quality of mixture of LBY and cassava
pulp (CVP) with rice straw (RS) in different ratios during preservation periods.
Four mixtures of LBY, CVP and RS were made, that is mixture ratio of LBY : CVP :
RS of 0% LBY, 20% LBY, 35% LBY and 50% LBY were 0:70:30, 20:50:30, 35:35:30 and
50:20:30 as fresh matter, respectively. The bags were opened at weeks 0, 1, 2, 4
and 8 after storage. The contents of dry matter, organic matter, crude protein
(CP), ether extract (EE), neutral detergent fiber and acid detergent fiber ranged
36.4-40.0, 88.9-90.8, 4.0-12.0, 1.1-1.3, 58.8-61.6 and 37.6-40.0, respectively,
and the contents of CP and EE increased and the other components decreased in
proportion to LBY inclusion (P < 0.01). 50% LBY had the highest (P < 0.05) pH
(4.81) and ammonia nitrogen per total nitrogen (NH3 -N/TN) (7.40%) and the lowest
V-score (90.3). Propionic and butyric acid contents were 0.01% or lower in each
mixture and storage period. There were rapid pH decrease and NH3 -N/TN increase
during the first week of the storage period. The increases of NH3 -N/TN and
acetic acid content and decreases of pH, lactic acid content and V-score during
the preservation were more drastic as LBY inclusion increased. Although higher
proportion of LBY produced higher CP and lower fiber contents in the mixture,
attention should be paid for the reduction of fermentation quality during longer
storage periods.
PMID- 27611884
TI - Conformal Electroplating of Azobenzene-Based Solar Thermal Fuels onto Large-Area
and Fiber Geometries.
AB - There is tremendous growth in fields where small functional molecules and
colloidal nanomaterials are integrated into thin films for solid-state device
applications. Many of these materials are synthesized in solution and there often
exists a significant barrier to transition them into the solid state in an
efficient manner. Here, we develop a methodology employing an electrodepositable
copolymer consisting of small functional molecules for applications in solar
energy harvesting and storage. We employ azobenzene solar thermal fuel polymers
and functionalize them to enable deposition from low concentration solutions in
methanol, resulting in uniform and large-area thin films. This approach enables
conformal deposition on a variety of conducting substrates that can be either
flat or structured depending on the application. Our approach further enables
control over film growth via electrodepsition conditions and results in highly
uniform films of hundreds of nanometers to microns in thickness. We demonstrate
that this method enables superior retention of solar thermal fuel properties,
with energy densities of ~90 J/g, chargeability in the solid state, and
exceptional materials utilization compared to other solid-state processing
approaches. This novel approach is applicable to systems such as photon
upconversion, photovoltaics, photosensing, light emission, and beyond, where
small functional molecules enable solid-state applications.
PMID- 27611883
TI - Postpolymerization modification of a hydroxy monolith precursor. Part I. Epoxy
alkane and octadecyl isocyanate modified poly (hydroxyethyl methacrylate-co
pentaerythritol triacrylate) monolithic capillary columns for reversed-phase
capillary electrochromatography.
AB - A novel precursor monolithic capillary column referred to as "hydroxy monolith"
or OHM was prepared by the in situ copolymerization of hydroxyethylmethacrylate
(HEMA) with pentaerythritol triacrylate (PETA) yielding the neutral poly(HEMA-co
PETA) monolith. The neutral precursor OHM capillary thus obtained was subjected
to postpolymerization modifications of the hydroxyl functional groups present on
its surface with 1,2-epoxyalkanes catalyzed by boron trifluoride (BF3 )
ultimately providing Epoxy OHM C-m capillary column at varying alkyl chain
lengths where m = 8, 12, 14, and 16 for RP-CEC. Also, the same precursor OHM was
grafted with octadecyl isocyanate yielding Isocyanato OHM C-18 column to provide
an insight into the effect of the nature of the linkage to the surface hydroxyl
groups of the OHM precursor. While the epoxide reaction leaves on the surface of
the OHM precursor hydroxy-ether linkages, the isocyanato reaction leaves
carbamate linkages on the same surface of the OHM precursor. This study revealed
that changing the alkyl chain length resulted in changing the column phase ratio
(phi) and also the solute distribution constant (K). While increasing the surface
alkyl chain length increased steeply the solute hydrophobic selectivity, i.e.
methylene group selectivity, the nature of the ligand linkage produced different
retention for the same solutes and affected the selectivity of slightly polar
solutes. The various monoliths proved very useful for RP-CEC of different small
solutes at varying polarity over a wide range of mobile phase composition.
PMID- 27611885
TI - Pain, Itch, Quality of Life, and Costs after Herpes Zoster.
AB - BACKGROUND: Herpes zoster (HZ) and postherpetic neuralgia are known to have a
profound effect on the patient's quality of life, but the incidence and severity
of itch and its relation with pain and quality of life in the long term are still
relatively unknown. OBJECTIVE: The aim of this study was to measure the presence
and severity of pain and itch and impact on quality of life in patients over 50
years old with HZ. METHODS: We enrolled 661 patients with HZ in this 12-month
observational study. Patient data were collected via a web-based questionnaire.
Outcomes were pain, itch, burden of illness, impact on patient's daily life,
impact on quality of life, and healthcare costs. RESULTS: At inclusion, 94% of
patients reported any pain, 74.3% significant pain, and 26% severe pain. After 3
months, 18.8% of patients suffered from postherpetic neuralgia. At inclusion,
70.8% of patients had any itch, 39.2% significant itch, and 7.3% severe itch. The
occurrence of pain increases costs and has a high impact on the quality of life,
lowering EQ-5D scores by an average of 18%. In contrast, itch has little effect
on the quality of life. CONCLUSIONS: Pain and itch are highly prevalent months
after HZ. Pain caused by HZ has a large impact on quality of life, burden of
illness, impact on daily life, and health care costs for these patients. The
impact of itch on quality of life is relatively small.
PMID- 27611886
TI - The Use of Stereology Method to Estimate the Volume of Feto-Maternal Exchange
Area of the Bovine Placentome during Gestation.
AB - The functional surface areas of the feto-maternal unit of the bovine placentomes
were quantified from Day 100 to 260 of gestation by using stereology. This study
was achieved using intact placentomes obtained from an abattoir. There was no
change in volume and surface densities of binucleate cells, fetal trophoblast,
fetal and maternal tissues, and maternal epithelium with gestation age, although
the total volume of these components increased with gestation age from Day 126 to
260. The total surface area of the feto-maternal interface increased in a similar
pattern as the placentomal components without a change in the fetal to maternal
tissue ratio when estimated with stereology. This is one of the recent studies in
cattle to quantify and describe the functional surface area of intact placentomes
at different stages of gestation and it emphasised the differences between the
yak and cattle placentomal development. Anat Rec, 299:1571-1577, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27611887
TI - Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR1 Transporter
on Pantoprazole Metabolism and Helicobacter pylori Eradication.
AB - Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of
peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes
CYP2C19 and CYP3A4. Pantoprazole is a substrate for multi-drug resistance protein
1 (MDR1). Single nucleotide polymorphisms (SNPs) in CYP2C19, CYP3A4 and MDR1
affect enzyme activity or gene expression of proteins and may alter plasma
pantoprazole concentrations and treatment success in PUD. In this study, we aimed
to investigate the association between genetic polymorphisms in CYP2C19, CYP3A4
and MDR1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients
with either Helicobacter pylori-associated [H.P.(+)]-PUD or [H.P.(+)]-gastritis.
The plasma pantoprazole concentrations were determined by using an HPLC method at
the third hour after a 40-mg tablet of pantoprazole administration in 194 newly
diagnosed patients with either [H.P.(+)]-PUD or [H.P.(+)]-gastritis. Genotyping
was performed by using PCR-RFLP and DNA sequencing. Among patients appearing for
follow-up examination (n = 105), the eradication rate for H. pylori was 82.8% (n
= 87). The median pantoprazole plasma concentrations in poor metabolizers (PM),
rapid metabolizers (RM) and ultrarapid metabolizers (URM) were 2.07, 1.69 and
1.28 MUg/ml, respectively (p = 0.04). CYP3A4*1G and *22 polymorphisms did not
affect plasma pantoprazole concentrations and H. pylori eradication rate. The
MDR1 genetic polymorphisms did not affect plasma pantoprazole concentrations.
MDR1 3435CC-2677GG-1236CC haplotype carriers had lower H. pylori eradication rate
(60%) than the remaining subjects (84.9%) while the difference was not
statistically significant (p = 0.07). In conclusion, while CYP2C19 genetic
polymorphisms significantly affected plasma pantoprazole concentrations,
polymorphisms of CYP2C19, CYP3A4 and MDR1 did not affect H. pylori eradication
rates.
PMID- 27611889
TI - Limits of RNA 2'-OH Mimicry by Fluorine: Crystal Structure of Bacillus halodurans
RNase H Bound to a 2'-FRNA:DNA Hybrid.
AB - RNase H1 cleaves the RNA strand of RNA:DNA hybrids. Replacement of RNA 2'
hydroxyls by fluorine (FRNA) is commonly used to stabilize aptamers and siRNAs.
However, FRNA:DNA hybrids fail to elicit RNase H activity. The underlying reasons
are unclear, as 2'-OH groups are not directly involved in cleavage. We determined
the crystal structure of Bacillus halodurans RNase H bound to a FRNA:DNA hybrid.
The structure points to dynamic (slippage of the FRNA:DNA hybrid relative to the
enzyme), geometric (different curvatures of FRNA:DNA and RNA:DNA hybrids), and
electronic reasons (Mg(2+) absent from the active site of the FRNA:DNA complex)
for the loss of RNaseH activity.
PMID- 27611888
TI - Levels of inflammation and oxidative stress, and a role for taurine in
dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne
Muscular Dystrophy.
AB - Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting disease
presenting with excessive myofibre necrosis and increased inflammation and
oxidative stress. In the mdx mouse model of DMD, homeostasis of the amino acid
taurine is altered, and taurine administration drastically decreases muscle
necrosis, dystropathology, inflammation and protein thiol oxidation. Since the
severe pathology of the Golden Retriever Muscular Dystrophy (GRMD) dog model more
closely resembles the human DMD condition, we aimed to assess the generation of
oxidants by inflammatory cells and taurine metabolism in this species. In muscles
of 8 month GRMD dogs there was an increase in the content of neutrophils and
macrophages, and an associated increase in elevated myeloperoxidase, a protein
secreted by neutrophils that catalyses production of the highly reactive
hypochlorous acid (HOCl). There was also increased chlorination of tyrosines, a
marker of HOCl generation, increased thiol oxidation of many proteins and
irreversible oxidative protein damage. Taurine, which functions as an antioxidant
by trapping HOCl, was reduced in GRMD plasma; however taurine was increased in
GRMD muscle tissue, potentially due to increased muscle taurine transport and
synthesis. These data indicate a role for HOCl generated by neutrophils in the
severe dystropathology of GRMD dogs, which may be exacerbated by decreased
availability of taurine in the blood. These novel data support continued research
into the precise roles of oxidative stress and taurine in DMD and emphasise the
value of the GRMD dogs as a suitable pre-clinical model for testing taurine as a
therapeutic intervention for DMD boys.
PMID- 27611890
TI - Micro-Computed Tomography Comparison of Preterminal Bronchioles in Centrilobular
and Panlobular Emphysema.
AB - RATIONALE: Very little is known about airways that are too small to be visible on
thoracic multidetector computed tomography but larger than the terminal
bronchioles. OBJECTIVES: To examine the structure of preterminal bronchioles
located one generation proximal to terminal bronchioles in centrilobular and
panlobular emphysema. METHODS: Preterminal bronchioles were identified by
backtracking from the terminal bronchioles, and their centerlines were
established along the entire length of their lumens. Multiple cross-sectional
images perpendicular to the centerline were reconstructed to evaluate the
bronchiolar wall and lumen, and the alveolar attachments to the outer airway
walls in relation to emphysematous destruction in 28 lung samples from six
patients with centrilobular emphysema, 20 lung samples from seven patients with
panlobular emphysema associated with alpha-1 antitrypsin deficiency, and 47
samples from seven control (donor) lungs. MEASUREMENTS AND MAIN RESULTS: The
preterminal bronchiolar length, wall volume, total volume (wall + lumen), lumen
circularity, and number of alveolar attachments were reduced in both
centrilobular and panlobular emphysema compared with control lungs. In contrast,
thickening of the wall and narrowing of the lumen were more severe and
heterogeneous in centrilobular than in panlobular emphysema. The bronchiolar
lumen was narrower in the middle than at both ends, and the decreased number of
alveolar attachments was associated with increased wall thickness in
centrilobular emphysema. CONCLUSIONS: These results provide new information about
small airways pathology in centrilobular and panlobular emphysema and show that
these changes affect airways that are not visible with thoracic multidetector
computed tomography scans but located proximal to the terminal bronchioles in
chronic obstructive pulmonary disease.
PMID- 27611891
TI - Resolving variable maternal D typing using serology and genotyping in selected
prenatal patients.
AB - BACKGROUND: RhIG prophylaxis for D- pregnant women prevents hemolytic disease of
the newborn and typically depends on results of serologic D typing.
Interpretation and follow-up of weak D serology is variable. Recent
recommendations promote genotyping for RHD status determination in those with
weak D serology. Canadian Blood Services performs comprehensive serologic
prenatal testing in four provinces. Genotyping is used to determine D typing in
patients with weak D. STUDY DESIGN AND METHODS: A serologic algorithm identified
which patients require genotyping for RHD determination. Genotyping was performed
on one of two commercially available platforms. RESULTS: Only 0.4% of D- patients
met criteria for genotyping. Sixty-one percent were weak D Type 1, 2, or 3.
Thirty percent had a partial or weak D other than Type 1, 2, or 3. Eleven had
variants which remained unresolved. Seventeen were D+ and four were D-.
CONCLUSIONS: Genotyping of patients with weak D serology led to an identified
genotype in most patients. RhIG administration was avoided in 66% who were weak D
Type 1, 2, or 3 or were D+. The use of a serologic algorithm to select patients
for RHD genotyping identifies a majority of patients with weak D types not at
risk for alloimmunization. This approach limits the number of genotyping
investigations and the cost of providing classification for weak D types.
PMID- 27611892
TI - Shared Decision Making to Support the Provision of Palliative and End-of-Life
Care in the Emergency Department: A Consensus Statement and Research Agenda.
AB - BACKGROUND: Little is known about the optimal use of shared decision making (SDM)
to guide palliative and end-of-life decisions in the emergency department (ED).
OBJECTIVE: The objective was to convene a working group to develop a set of
research questions that, when answered, will substantially advance the ability of
clinicians to use SDM to guide palliative and end-of-life care decisions in the
ED. METHODS: Participants were identified based on expertise in emergency,
palliative, or geriatrics care; policy or patient-advocacy; and spanned
physician, nursing, social work, legal, and patient perspectives. Input from the
group was elicited using a time-staggered Delphi process including three
teleconferences, an open platform for asynchronous input, and an in-person
meeting to obtain a final round of input from all members and to identify and
resolve or describe areas of disagreement. CONCLUSION: Key research questions
identified by the group related to which ED patients are likely to benefit from
palliative care (PC), what interventions can most effectively promote PC in the
ED, what outcomes are most appropriate to assess the impact of these
interventions, what is the potential for initiating advance care planning in the
ED to help patients define long-term goals of care, and what policies influence
palliative and end-of-life care decision making in the ED. Answers to these
questions have the potential to substantially improve the quality of care for ED
patients with advanced illness.
PMID- 27611893
TI - Digenic inheritance in epidermolysis bullosa simplex involving two novel
mutations in KRT5 and KRT14.
PMID- 27611895
TI - (Un)Disciplined futures: Women of color feminism as a disruptive to white affect
studies.
AB - The aim of this article is to demonstrate how women of color feminism predates
and disrupts dominant dialogues in the field of White affect studies. I introduce
the concept of White affect studies as an arena of inquiry that draws from
Western-European theories and literatures and architects a sociopolitical
structure of affect that positions White affects as universal. Scholars
contributing to the field of White affect studies posit theories of affect,
embodiment, subjectivity, phenomenology, violence, war, and more, while
disregarding the theoretical contributions made by women of color feminism in
thinking through these notions and social issues. This is done by engaging in a
citational practice that results in an epistemic erasure of women of color
feminist thought. The voices of women of color feminists are thus disqualified,
and their theoretical contributions are not acknowledged as significant or
relevant in conceptualizing affect, affective economies, and the social. By
turning to the writings of women of color feminists, I demonstrate how their
theories on embodiment, subjectivity, and social structures predate the
institutionalization of White affect studies. Feminists of color from the past
and present have and continue to theorize through a language of self their
experiences as subjects embedded within matrices of violence, power, and
pleasure. Lorde, Martinez, and Chinchilla write about the ways in which lesbian
and queer women of color institute different affects that counter dominant
structures of emotion, systems of power, and heterosexual modes of being. In
developing conceptual methodologies, Lorde, Martinez, and Chinchilla are able to
weave into the dominant discursive logic a language of self that both introduces
new queer subjectivities, while reinterpreting existing forms of thought, thereby
contesting mainstream economies of White affects and White affect studies. It is
through a language of self that Lorde, Martinez, and Chinchilla develop an ethic
of survival that countermobilizes against White hegemonic apparatuses.
PMID- 27611894
TI - Promoting Undergraduate Surgical Education: Current Evidence and Students' Views
on ESMSC International Wet Lab Course.
AB - BACKGROUND: Undergraduate Surgical Education is becoming an essential element in
the training of the future generation of safe and efficient surgeons. Essential
Skills in the Management of Surgical Cases (ESMSC), is an international, joint
applied surgical science and simulation-based learning wet lab course. METHODS:
We performed a review of the existing literature on the topic of undergraduate
surgical education. Following that, we analyzed the feedback questionnaire
received 480 from 2 recent series of ESMSC courses (May 2015, n = 49 and November
2015, n = 40), in order to evaluate European Union students' (UK, Germany,
Greece) views on the ESMSC course, as well as on the undergraduate surgical
education. Results Using a 10 point graded scale, the overall ESMSC concept was
positively evaluated, with a mean score of 9.41 +/- 0.72 (range: 8-10) and 8.94
+/- 1.1 (range: 7-10). The majority of delegates from both series [9.86 +/- 0.43
(range: 8-10) and 9.58 +/- 0.91 (range: 6-10), respectively] believed that ESMSC
should be incorporated in the undergraduate surgical curriculum. Comparison of
responses from the UK to the Greek Medical Student, as well as the findings from
the third and fourth year versus the fifth and sixth year Medical Students,
revealed no statistically significant differences pertaining to any of the
questions (p > 0.05). CONCLUSIONS: Current evidence in the literature supports
the enhancement of surgical education through the systematic use of various
modalities that provide Simulation-Based Training (SBT) hands-on experience,
starting from the early undergraduate level. The findings of the present study
are in agreement with these previous reports.
PMID- 27611896
TI - Endoscopic posterior interhemispheric complete corpus callosotomy.
AB - Traditionally corpus callosotomy is done through a craniotomy centered at the
coronal suture, with the aid of a microscope. This involves dissecting through
the interhemispheric fissure below the falx to reach the corpus callosum. The
authors describe a posterior interhemispheric approach to complete corpus
callosotomy with an endoscope, which bypasses the need to perform
interhemispheric dissection because the falx is generally close to the corpus
callosum in this region.
PMID- 27611897
TI - Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with
intracranial vascular anomalies.
AB - OBJECTIVE Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a
rare genetic disorder. Features of it include extremely small stature, severe
microcephaly, and normal or near-normal intelligence. Previous studies have found
that more than 50% of patients with MOPD II have intracranial vascular anomalies,
but few successful surgical revascularization or aneurysm-clipping cases have
been reported because of the diminutive arteries and narrow surgical corridors in
these patients. Here, the authors report on a large series of patients with MOPD
II who underwent surgery for an intracranial vascular anomaly. METHODS In
conjunction with an approved prospective registry of patients with MOPD II, a
prospectively collected institutional surgical database of children with MOPD II
and intracranial vascular anomalies who underwent surgery was analyzed
retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD
II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease
(MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients
presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2),
intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid
hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8
patients with MMD, all of whom underwent extracranial-intracranial
revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The
mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two
patients experienced postoperative complications (1 transient weakness after
clipping, 1 femoral thrombosis that required surgical repair). During a mean
follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid
hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient
had continued TIAs. All of the surviving patients recovered to their neurological
baseline. CONCLUSIONS Patients with MMD presented at a younger age than those in
whom aneurysms were more prevalent. Microneurosurgery with either intracranial
bypass or aneurysm clipping is extremely challenging but feasible at expert
centers in patients with MOPD II, and good long-term outcomes are possible.
PMID- 27611898
TI - Presurgical evaluation of pediatric epilepsy patients prior to hemispherotomy:
the prognostic value of 18F-FDG PET.
AB - OBJECTIVE The objective of this study was to investigate whether fluorine-18
fluorodeoxyglucose PET (18F-FDG PET) can help to predict seizure outcome after
hemispherotomy and therefore may be useful in decision making and patient
selection. METHODS Children and adolescents less than 18 years of age who
underwent 18F-FDG PET studies during presurgical evaluation prior to
hemispherotomy and had follow-up data of at least 12 months after surgery were
included. Seizure outcome was classified according to the recommendations of the
International League Against Epilepsy. PET data were reevaluated by two
specialists in nuclear medicine blinded to clinical data and to MRI. MRI studies
were also reinterpreted visually by an experienced neuroradiologist blinded to
clinical data and PET findings. RESULTS Thirty-five patients (17 girls) with a
median age of 5 years (range 0.4-17.8 years) were evaluable. Of the 35 patients,
91.4% were seizure free after surgery, including 100% of those with unilateral
18F-FDG-PET hypometabolism compared with only 75% of those with bilateral
hypometabolism. With respect to MRI, seizure freedom after surgery was observed
in 96.4% of the patients with unilateral lesions compared with only 71.4% in
those with bilateral MRI lesions. The best seizure outcomes were noted in
patients with unilateral findings in both PET and MRI (100% seizure freedom)
whereas only 50% of those with bilateral findings in both imaging techniques were
seizure free. Furthermore, 100% of the patients with unilateral PET
hypometabolism and bilateral MRI findings were also seizure free, but only 87.5%
of those with bilateral PET hypometabolism and unilateral MRI findings.
CONCLUSIONS According to these results, candidate selection for hemispherotomy
can be optimized by the use of 18F-FDG PET as part of a multimodal presurgical
evaluation program, especially in patients with inconsistent (bilateral) MRI
findings.
PMID- 27611899
TI - Endoscope-assisted management of sagittal synostosis: wide vertex suturectomy and
barrel stave osteotomies versus narrow vertex suturectomy.
AB - OBJECTIVE Endoscope-assisted methods for treatment of craniosynostosis have
reported benefits over open calvarial vault reconstruction. In this paper, the
authors evaluated 2 methods for endoscope-assisted correction of sagittal
synostosis: wide vertex suturectomy and barrel stave osteotomies (WVS+BSO) and
narrow vertex suturectomy (NVS). METHODS The authors evaluated patients with
nonsyndromic sagittal synostosis treated with either wide vertex suturectomy (4-6
cm) and barrel stave osteotomies (WVS+BSO) or narrow vertex suturectomy (NVS)
(approximately 2 cm) between October 2006 and July 2013. Prospectively collected
data included patient age, sex, operative time, estimated blood loss (EBL),
postoperative hemoglobin level, number of transfusions, complications, and
cephalic index. Fourteen patients in the NVS group were age matched to 14
patients in the WVS+BSO group. Descriptive statistics were calculated, and
Student t-tests were used to compare prospectively obtained data from the WVS+BSO
group with the NVS group in a series of univariate analyses. RESULTS The mean age
at surgery was 3.9 months for WVS+BSO and 3.8 months for NVS. The mean operative
time for patients undergoing NVS was 59.0 minutes, significantly less than the
83.4-minute operative time for patients undergoing WVS+BSO (p < 0.05). The
differences in mean EBL (NVS: 25.4 ml; WVS+BSO: 27.5 ml), mean postoperative
hemoglobin level (NVS: 8.6 g/dl; WVS+BSO: 8.0 g/dl), mean preoperative cephalic
index (NVS: 69.9; WVS+BSO: 68.2), and mean cephalic index at 1 year of age (NVS:
78.1; WVS+BSO: 77.2) were not statistically significant. CONCLUSIONS The NVS and
WVS+BSO produced nearly identical clinical results, as cephalic index at 1 year
of age was similar between the 2 approaches. However, the NVS required fewer
procedural steps and significantly less operative time than the WVS+BSO. The NVS
group obtained the final cephalic index in a similar amount of time
postoperatively as the WVS+BSO group. Complications, transfusion rates, and EBL
were not different between the 2 techniques.
PMID- 27611900
TI - In situ repair of vagus nerve stimulator lead damage: technical note.
AB - Vagus nerve stimulators (VNSs) are currently an accepted treatment for
intractable epilepsy not amenable to ablative surgery. Battery death and lead
damage are the main reasons for reoperation in patients with VNSs. In general,
any damage to the lead requires revision surgery to remove the helical electrodes
from the vagus nerve and replace the electrode array and wire. The electrodes are
typically scarred and difficult to remove from the vagus nerve without injury.
The authors describe 6 patients with VNSs who presented with low lead impedance
on diagnostic testing, leading to the intraoperative finding of lead insulation
disruption, or who were found incidentally at the time of implantable pulse
generator battery replacement to have a tear in the outer insulation of the
electrode wire. Instead of replacement, the wire insulation was repaired and
reinforced in situ, leading to normal impedance testing. All 6 devices remained
functional over a follow-up period of up to 87 months, with 2 of the 6 patients
having a relatively shorter follow-up of only 12 months. This technique,
applicable in a subset of patients with VNSs requiring lead exploration, obviates
the need for lead replacement with its attendant risks.
PMID- 27611901
TI - Osmotic Pressure in Clinical Medicine with an Emphasis on Dialysis.
AB - Since the beginning of life of the first multicellular organisms, the
preservation of a physiologic milieu for every cell in the organism has been a
critical requirement. A particular range of osmolality of the body fluids is
essential for the maintenance of cell volume. In humans the stability of
electrolyte concentrations and their resulting osmolality in the body fluids is
the consequence of complex interactions between cell membrane functions, hormonal
control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge
of these mechanisms, of the biochemical principles of osmolality, and of the
relevant situations occurring in disease is of importance to every physician.
This comprehensive review summarizes the major facts on osmolality, its relation
to electrolytes and other solutes, and its relevance in physiology and in disease
states with a focus on dialysis-related considerations.
PMID- 27611902
TI - Analysis of Loops that Mediate Protein-Protein Interactions and Translation into
Submicromolar Inhibitors.
AB - Effective strategies for mimicking alpha-helix and beta-strand epitopes have been
developed, producing valuable inhibitors for some classes of protein-protein
interactions (PPIs). However, there are no general strategies for translating
loop epitopes into useful PPI inhibitors. In this work, we use the LoopFinder
program to identify diverse sets of "hot loops," which are loop epitopes that
mediate PPIs. These include loops that are well-suited to mimicry with
macrocyclic compounds, and loops that are most similar to variable loops on
antibodies and ankyrin repeat proteins. We present data-driven criteria for
scoring loop-mediated PPIs, uncovering a trove of potentially druggable
interactions. We also use unbiased clustering to identify common structures among
the hot loops. To translate these insights into real-world inhibitors, we
describe a robust, diversity-oriented strategy for the rapid production and
evaluation of cyclized loops. This method is applied to a computationally
identified loop in the PPI between stonin2 and Eps15, producing submicromolar
inhibitors. The most potent inhibitor is well-structured in water and
successfully mimics the native epitope. Overall, these computational and
experimental strategies provide new opportunities to design inhibitors for an
otherwise intractable set of PPIs.
PMID- 27611903
TI - Exercise for depression in older adults: a meta-analysis of randomized controlled
trials adjusting for publication bias.
AB - OBJECTIVE: To evaluate the antidepressant effects of exercise in older adults,
using randomized controlled trial (RCT) data. METHODS: We conducted a meta
analysis of exercise in older adults, addressing limitations of previous works.
RCTs of exercise interventions in older people with depression (>= 60 years)
comparing exercise vs. control were eligible. A random-effects meta-analysis
calculating the standardized mean difference (SMD) (95% confidence interval
[95%CI]), meta-regressions, and trim, fill, and fail-safe number analyses were
conducted. RESULTS: Eight RCTs were included, representing 138 participants in
exercise arms and 129 controls. Exercise had a large and significant effect on
depression (SMD = -0.90 [95%CI -0.29 to -1.51]), with a fail-safe number of 71
studies. Significant effects were found for 1) mixed aerobic and anaerobic
interventions, 2) at moderate intensity, 3) that were group-based, 4) that
utilized mixed supervised and unsupervised formats, and 5) in people without
other clinical comorbidities. CONCLUSION: Adjusting for publication bias
increased the beneficial effects of exercise in three subgroup analysis,
suggesting that previous meta-analyses have underestimated the benefits of
exercise due to publication bias. We advocate that exercise be considered as a
routine component of the management of depression in older adults.
PMID- 27611905
TI - National trends in heart failure hospitalization rates in Slovenia 2004-2012.
AB - AIMS: Heart failure (HF) hospitalization rates are decreasing in western Europe,
but little is known about trends in central and east European countries. We
analysed the Slovenian national hospitalization database to determine the burden
of HF hospitalization. METHODS AND RESULTS: The Slovenian National Hospital
Discharge Registry was searched for HF hospitalizations between 2004 and 2012 in
patients aged >=20 years. A total of 55 531 main HF hospitalizations (43 636
first HF hospitalizations) in 34 406 patients (median age 78 years, 55% female)
were recorded. The most common co-morbidities were arterial hypertension (54.3%),
atrial fibrillation (40.6%), diabetes mellitus (24.5%), and ischaemic heart
disease (21.9%). The number of age-standardized main and first HF
hospitalizations per 100 000 population decreased from 249 to 232 (7.1%, P =
0.002) and from 467 to 435 (6.8%, P = 0.074), respectively. Crude main and first
HF hospitalization rates increased from 249 to 298 (19.8%, P < 0.001) and from
530 to 558 (5.4%, P = 0.100), respectively. After a first HF hospitalization, any
HF readmission rates within 30, 60, and 90 days and at 1 year were 11.7, 17.2,
20.9, and 37.5%, respectively. Hospitalization trends were similar in both sexes
and across all age groups. In a multivariate log binomial regression model,
myocardial infarction, chronic kidney disease, diabetes mellitus, male sex, and
year of admission were independently associated with higher HF readmission rates
(P < 0.01 for all). CONCLUSIONS: In Slovenia, standardized HF hospitalization
rates have decreased but the crude HF hospitalization burden has increased.
Readmissions were associated with established cardiovascular risk factors.
PMID- 27611904
TI - Aldo-keto reductase enzymes detoxify glyphosate and improve herbicide resistance
in plants.
AB - In recent years, concerns about the use of glyphosate-resistant crops have
increased because of glyphosate residual levels in plants and development of
herbicide-resistant weeds. In spite of identifying glyphosate-detoxifying genes
from microorganisms, the plant mechanism to detoxify glyphosate has not been
studied. We characterized an aldo-keto reductase gene from Pseudomonas (PsAKR1)
and rice (OsAKR1) and showed, by docking studies, both PsAKR1 and OsAKR1 can
efficiently bind to glyphosate. Silencing AKR1 homologues in rice and Nicotiana
benthamiana or mutation of AKR1 in yeast and Arabidopsis showed increased
sensitivity to glyphosate. External application of AKR proteins rescued
glyphosate-mediated cucumber seedling growth inhibition. Regeneration of tobacco
transgenic lines expressing PsAKR1 or OsAKRI on glyphosate suggests that AKR can
be used as selectable marker to develop transgenic crops. PsAKR1- or OsAKRI
expressing tobacco and rice transgenic plants showed improved tolerance to
glyphosate with reduced accumulation of shikimic acid without affecting the
normal photosynthetic rates. These results suggested that AKR1 when overexpressed
detoxifies glyphosate in planta.
PMID- 27611906
TI - Preovulatory Aging In Vivo and In Vitro Affects Maturation Rates, Abundance of
Selected Proteins, Histone Methylation Pattern and Spindle Integrity in Murine
Oocytes.
AB - Delayed ovulation and delayed fertilization can lead to reduced developmental
competence of the oocyte. In contrast to the consequences of postovulatory aging
of the oocyte, hardly anything is known about the molecular processes occurring
during oocyte maturation if ovulation is delayed (preovulatory aging). We
investigated several aspects of oocyte maturation in two models of preovulatory
aging: an in vitro follicle culture and an in vivo mouse model in which ovulation
was postponed using the GnRH antagonist cetrorelix. Both models showed
significantly reduced oocyte maturation rates after aging. Furthermore, in vitro
preovulatory aging deregulated the protein abundance of the maternal effect genes
Smarca4 and Nlrp5, decreased the levels of histone H3K9 trimethylation and caused
major deterioration of chromosome alignment and spindle conformation. Protein
abundance of YBX2, an important regulator of mRNA stability, storage and
recruitment in the oocyte, was not affected by in vitro aging. In contrast, in
vivo preovulatory aging led to reduction in Ybx2 transcript and YBX2 protein
abundance. Taken together, preovulatory aging seems to affect various processes
in the oocyte, which could explain the low maturation rates and the previously
described failures in fertilization and embryonic development.
PMID- 27611907
TI - Micro-/Mesoporous Platinum-SiCN Nanocomposite Catalysts (Pt@SiCN): From Design to
Catalytic Applications.
AB - The synthesis, characterization, and catalytic studies of platinum (Pt)
nanoparticles (NPs) supported by a polymer-derived SiCN matrix are reported. In
the first step and under mild conditions (110 degrees C), a block copolymer
(BCP) based on hydroxyl-group-terminated linear polyethylene (PEOH) and a
commercially available polysilazane (PSZ: HTT 1800) were synthesized. Afterwards,
the BCP was microphase separated, modified with an aminopyridinato (Ap) ligand
stabilized Pt complex, and cross-linked. The green bodies thus obtained were
pyrolyzed at 1000 degrees C under nitrogen and provided porous Pt@SiCN
nanocomposite via decomposition of the PEOH block while Pt nanoparticles grew in
situ within the SiCN matrix. Powder X-ray diffraction (PXRD) studies confirmed
the presence of the cubic Pt phase in the amorphous SiCN matrix whereas
transmission electron microscopy (TEM) measurements revealed homogeneously
distributed Pt nanoparticles in the size of 0.9 to 1.9 nm. N2 sorption studies
indicated the presence of micro- and mesopores. Pt@SiCN appears to be an active
and robust catalyst in the hydrolysis of sodium borohydride under harsh
conditions.
PMID- 27611909
TI - Specialised healthcare resident tutors' training needs in the Balearic Islands.
PMID- 27611908
TI - Mitigating Financial Burden of Tuberculosis through Active Case Finding Targeting
Household and Neighbourhood Contacts in Cambodia.
AB - BACKGROUND: Despite free TB services available in public health facilities, TB
patients often face severe financial burden due to TB. WHO set a new global
target that no TB-affected families experience catastrophic costs due to TB. To
monitor the progress and strategize the optimal approach to achieve the target,
there is a great need to assess baseline cost data, explore potential proxy
indicators for catastrophic costs, and understand what intervention mitigates
financial burden. In Cambodia, nationwide active case finding (ACF) targeting
household and neighbourhood contacts was implemented alongside routine passive
case finding (PCF). We analyzed household cost data from ACF and PCF to determine
the financial benefit of ACF, update the baseline cost data, and explore whether
any dissaving patterns can be a proxy for catastrophic costs in Cambodia.
METHODS: In this cross-sectional comparative study, structured interviews were
carried out with 108 ACF patients and 100 PCF patients. Direct and indirect
costs, costs before and during treatment, costs as percentage of annual household
income and dissaving patterns were compared between the two groups. RESULTS: The
median total costs were lower by 17% in ACF than in PCF ($240.7 [IQR 65.5-594.6]
vs $290.5 [IQR 113.6-813.4], p = 0.104). The median costs before treatment were
significantly lower in ACF than in PCF ($5.1 [IQR 1.5-25.8] vs $22.4 [IQR 4.4
70.8], p<0.001). Indirect costs constituted the largest portion of total costs
(72.3% in ACF and 61.5% in PCF). Total costs were equivalent to 11.3% and 18.6%
of annual household income in ACF and PCF, respectively. ACF patients were less
likely to dissave to afford TB-related expenses. Costs as percentage of annual
household income were significantly associated with an occurrence of selling
property (p = 0.02 for ACF, p = 0.005 for PCF). CONCLUSIONS: TB-affected
households face severe financial hardship in Cambodia. ACF has the great
potential to mitigate the costs incurred particularly before treatment. Social
protection schemes that can replace lost income are critically needed to
compensate for the most devastating costs in TB. An occurrence of selling
household property can be a useful proxy for catastrophic cost in Cambodia.
PMID- 27611910
TI - The rs251684 Variant of PLA2G4C Is Associated with Autism Spectrum Disorder in
the Northeast Han Chinese Population.
AB - AIM: To investigate the association between autism spectrum disorder (ASD) and
the phospholipase A2 group IVC (PLA2G4C) and phospholipase A2 group XIIA
(PLA2G12A) polymorphisms in the Northeast Han Chinese population. MATERIALS AND
METHODS: A total of 68 family trios (children diagnosed with ASD and their
unaffected parents) were enrolled. Five single-nucleotide polymorphisms (SNPs)
(rs9226, rs1045376, rs251684, rs2307279, and rs156631) in PLA2G4C and four SNPs
(rs6533451, rs2285714, rs2285713, and rs11728699) in PLA2G12A were selected and
genotyped. The association between the SNPs and ASD was analyzed using the
transmission disequilibrium test. RESULTS: Our results showed a significant
association between ASD and the rs251684 variant of PLA2G4C
(transmitted/nontransmitted = 36/21, chi2 = 3.947, p = 0.047), but no association
between ASD and the other eight SNPs investigated (all p > 0.05). Moreover, we
found no preference in the transmission of haplotypes constructed for either
PLA2G4C or PLA2G12A. CONCLUSION: The rs251684 polymorphism of PLA2G4C may be
associated with ASD risk.
PMID- 27611912
TI - Electronic Coupling Calculations for Bridge-Mediated Charge Transfer Using
Constrained Density Functional Theory (CDFT) and Effective Hamiltonian Approaches
at the Density Functional Theory (DFT) and Fragment-Orbital Density Functional
Tight Binding (FODFTB) Level.
AB - In this article, four methods to calculate charge transfer integrals in the
context of bridge-mediated electron transfer are tested. These methods are based
on density functional theory (DFT). We consider two perturbative Green's function
effective Hamiltonian methods (first, at the DFT level of theory, using localized
molecular orbitals; second, applying a tight-binding DFT approach, using fragment
orbitals) and two constrained DFT implementations with either plane-wave or local
basis sets. To assess the performance of the methods for through-bond (TB)
dominated or through-space (TS)-dominated transfer, different sets of molecules
are considered. For through-bond electron transfer (ET), several molecules that
were originally synthesized by Paddon-Row and co-workers for the deduction of
electronic coupling values from photoemission and electron transmission
spectroscopies, are analyzed. The tested methodologies prove to be successful in
reproducing experimental data, the exponential distance decay constant and the
superbridge effects arising from interference among ET pathways. For through
space ET, dedicated pi-stacked systems with heterocyclopentadiene molecules were
created and analyzed on the basis of electronic coupling dependence on donor
acceptor distance, structure of the bridge, and ET barrier height. The
inexpensive fragment-orbital density functional tight binding (FODFTB) method
gives similar results to constrained density functional theory (CDFT) and both
reproduce the expected exponential decay of the coupling with donor-acceptor
distances and the number of bridging units. These four approaches appear to give
reliable results for both TB and TS ET and present a good alternative to
expensive ab initio methodologies for large systems involving long-range charge
transfers.
PMID- 27611911
TI - Chronic Obstructive Pulmonary Disease Subtypes. Transitions over Time.
AB - BACKGROUND: Although subtypes of chronic obstructive pulmonary disease are
recognized, it is unknown what happens to these subtypes over time. Our
objectives were to assess the stability of cluster-based subtypes in patients
with stable disease and explore changes in clusters over 1 year. METHODS:
Multiple correspondence and cluster analysis were used to evaluate data collected
from 543 stable patients included consecutively from 5 respiratory outpatient
clinics. RESULTS: Four subtypes were identified. Three of them, A, B, and C, had
marked respiratory profiles with a continuum in severity of several variables,
while the fourth, subtype D, had a more systemic profile with intermediate
respiratory disease severity. Subtype A was associated with less dyspnea, better
health-related quality of life and lower Charlson comorbidity scores, and subtype
C with the most severe dyspnea, and poorer pulmonary function and quality of
life, while subtype B was between subtypes A and C. Subtype D had higher rates of
hospitalization the previous year, and comorbidities. After 1 year, all clusters
remained stable. Generally, patients continued in the same subtype but 28%
migrated to another cluster. Together with movement across clusters, patients
showed changes in certain characteristics (especially exercise capacity, some
variables of pulmonary function and physical activity) and changes in outcomes
(quality of life, hospitalization and mortality) depending on the new cluster
they belonged to. CONCLUSIONS: Chronic obstructive pulmonary disease clusters
remained stable over 1 year. Most patients stayed in their initial subtype
cluster, but some moved to another subtype and accordingly had different
outcomes.
PMID- 27611914
TI - Arrhythmia detection from heart rate variability by SDFA method.
AB - The smoothed detrended fluctuation analysis (SDFA) based on DFA and the principal
of wavelet shrinkage procedures is a scaling analysis method to represent the
correlation properties of a time series. Since there is not a specific rule for
the choice of the numbers of regressors in SDFA Method, we present here an
asymptotic optimal choice. We carried out some Monte Carlo simulations on
fractional Gaussian noise (FGN) models, to investigate the effect of the numbers
of regressors in SDFA Method. We analyze the long dependence property in view of
the SDFA method to compare 10 healthy and 10 unhealthy (with cardiac arrhythimia)
RR time series randomly selected from databases of the PhysioBank. It is proposed
that utilizing Hurst estimator by SDFA method, as an additional diagnostic tool
may provide an indication of cardiac arrhythmia.
PMID- 27611913
TI - Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior
Pituitary: Interplay between Nitric Oxide Pathway and Estrogen.
AB - Changes in the estrogenic status produce deep changes in pituitary physiology,
mainly because estrogens (E2) are one of the main regulators of pituitary cell
population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase
(nNOS) activity and expression and may thereby modulate the production of nitric
oxide (NO), an important regulator of cell death and survival. Little is known
about how ovary ablation affects anterior pituitary cell remodelling and
molecular mechanisms that regulate this process have not yet been elucidated. In
this work we used freshly dispersed anterior pituitaries as well as cell cultures
from ovariectomized female rats in order to study whether E2 deficiency induces
apoptosis in the anterior pituitary cells, the role of NO in this process and
effects of E2 on the NO pathway. Our results showed that cell activity gradually
decreases after ovariectomy (OVX) as a consequence of cell death, which is
completely prevented by a pan-caspase inhibitor. Furthermore, there is an
increase of fragmented nuclei and DNA cleavage thereby presenting the first
direct evidence of the existence of apoptosis in the anterior pituitary gland
after OVX. NO production and soluble guanylyl cyclase (sGC) expression in
anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of
both, NO synthase (NOS) and sGC activities prevented the drop of cell viability
after OVX, showing for the first time that increased NO levels and sGC activity
observed post-OVX play a key role in the induction of apoptosis. Conversely, E2
and prolactin treatments decreased nNOS expression and activity in pituitary
cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting
interplay between NO and E2 pathways in anterior pituitary.
PMID- 27611915
TI - A time-series analysis of the relation between unemployment rate and hospital
admission for acute myocardial infarction and stroke in Brazil over more than a
decade.
AB - BACKGROUND: The effect of socioeconomic stressors on the incidence of
cardiovascular disease (CVD) is currently open to debate. Using time-series
analysis, our study aimed to evaluate the relationship between unemployment rate
and hospital admission for acute myocardial infarction (AMI) and stroke in Brazil
over a recent 11-year span. METHODS AND RESULTS: Data on monthly hospital
admissions for AMI and stroke from March 2002 to December 2013 were extracted
from the Brazilian Public Health System Database. The monthly unemployment rate
was obtained from the Brazilian Institute for Applied Economic Research, during
the same period. The autoregressive integrated moving average (ARIMA) model was
used to test the association of temporal series. Statistical significance was set
at p<0.05. From March 2002 to December 2013, 778,263 admissions for AMI and
1,581,675 for stroke were recorded. During this time period, the unemployment
rate decreased from 12.9% in 2002 to 4.3% in 2013, while admissions due to AMI
and stroke increased. However, the adjusted ARIMA model showed a positive
association between the unemployment rate and admissions for AMI but not for
stroke (estimate coefficient=2.81+/-0.93; p=0.003 and estimate coefficient=2.40+/
4.34; p=0.58, respectively). CONCLUSIONS: From 2002 to 2013, hospital admissions
for AMI and stroke increased, whereas the unemployment rate decreased. However,
the adjusted ARIMA model showed a positive association between unemployment rate
and admissions due to AMI but not for stroke. Further studies are warranted to
validate our findings and to better explore the mechanisms by which socioeconomic
stressors, such as unemployment, might impact on the incidence of CVD.
PMID- 27611918
TI - The declining frequency of inducible myocardial ischemia during stress
echocardiography over 27 consecutive years (1983-2009).
AB - BACKGROUND: Previous studies have suggested a decline in positivity of stress
cardiac imaging, suggesting the need for developing better strategies for test
selection to achieve acceptable cost-effectiveness balance. The aim of this
retrospective study was to assess the rate of positivity of stress
echocardiography (SE) over 27 consecutive years. METHODS: We assessed the rate of
SE positivity in 2007 patients without previous myocardial infarction or coronary
revascularization who performed SE in a tertiary care referral center from 1983
to 2009. SE was performed with dipyridamole (1427), dobutamine (136) or exercise
(444). RESULTS: There was a progressive decline over time in the rate of SE
positivity from 42% (1983-1991) to 22% (2001-2009), with a relative increase of
patients with low pre-test probability of disease (from 5% to 27%). The
percentage of patients studied with SE under anti-ischemic therapy increased
markedly (from 8% in the first to 61% in the last nine years). CONCLUSION: Over
27 consecutive years, we observed a steady decline in SE positivity rate (with >5
fold increase of low probability patients), with almost 8-fold increase in anti
ischemic therapy at testing. We probably need refined criteria of referral for
testing and/or better ways to titrate the negative response beyond wall motion
abnormalities during SE.
PMID- 27611916
TI - Cardiac involvement in patients with rheumatic disorders: Data of the RHEU-M(A)R
study.
AB - BACKGROUND: The diagnosis of cardiac involvement in rheumatic disorders is
challenging due to its varying clinical presentation. Since clinical consequences
range from immediate treatment changes to adverse long-term outcome, individual
risk stratification is of great clinical interest. Primary aim was to evaluate
the prevalence of cardiac involvement in patients with different rheumatic
disorders using late gadolinium enhancement-cardiac magnetic resonance imaging
(LGE-CMR). In addition, we sought to investigate if different rheumatic disorders
would demonstrate different LGE patterns. METHODS: Two-hundred-ninety-seven
patients with rheumatic disorders were included and underwent LGE-CMR for work-up
of cardiac involvement, which was defined by the presence of LGE in the
myocardium. Patients were divided into five subgroups: 1) ANCA-associated
vasculitis, 2) non-ANCA-associated vasculitis, 3) connective tissue disorders, 4)
arthritis, and 5) sarcoidosis. RESULTS: Mean ejection fraction in the overall
population was 65%, with a mean age of 55yrs. Prevalence of cardiac involvement
in the five subgroups were as follows: 54% in the ANCA-associated vasculitis
group, 22% in the non-ANCA-associated vasculitis group, 14% in the group with
connective tissue disorders, 21% in the arthritis group, and 24% in sarcoid
patients. Each of the five subgroups demonstrated a distinct pattern of LGE.
CONCLUSION: There is a wide range in the prevalence of cardiac involvement in
different rheumatic disorders (54%-14%). Different groups of rheumatic disorders
demonstrate different patterns of LGE. CONDENSED ABSTRACT: Primary aim of the
study was to evaluate the presence of cardiac involvement in patients with
different rheumatic disorders using LGE-CMR. In addition, we sought to
investigate if different rheumatic disorders would reveal different LGE patterns.
In our 297 patients, the highest prevalence of cardiac involvement was found in
patients with ANCA-associated vasculitis (54%), whereas the lowest prevalence was
demonstrated in patients with connective tissue disorders (14%). Furthermore,
different groups of rheumatic disorders demonstrate distinct patterns of LGE.
PMID- 27611917
TI - Comparison of various scores for predicting success of chronic total occlusion
percutaneous coronary intervention.
AB - BACKGROUND: Various scoring systems have been developed to predict the technical
outcome and procedural efficiency of chronic total occlusion (CTO) percutaneous
coronary intervention (PCI). METHODS: We examined the predictive capacity of 3
CTO PCI scores (Clinical and Lesion-related [CL], Multicenter CTO registry in
Japan [J-CTO] and Prospective Global Registry for the Study of Chronic Total
Occlusion Intervention [PROGRESS CTO] scores) in 664 CTO PCIs performed between
2012 and 2016 at 13 US centers. RESULTS: Technical success was 88% and the
retrograde approach was utilized in 41%. Mean CL, J-CTO and PROGRESS CTO scores
were 3.9+/-1.9, 2.6+/-1.2 and 1.4+/-1.0, respectively. All scores were inversely
associated with technical success (p<0.001 for all) and had moderate
discriminatory capacity (area under the curve 0.691 for the CL score, 0.682 for
the J-CTO score and 0.647 for the PROGRESS CTO score [p=non-significant for
pairwise comparisons]). The difference in technical success between the minimum
and maximum CL score strata was the highest (32%, vs. 15% for J-CTO and 18% for
PROGRESS CTO scores). All scores tended to perform better in antegrade-only
procedures and correlated significantly with procedure time and fluoroscopy dose;
the CL score also correlated significantly with contrast utilization.
CONCLUSIONS: CL, J-CTO and PROGRESS CTO scores perform moderately in predicting
technical outcome of CTO PCI, with better performance for antegrade-only
procedures. All scores correlate with procedure time and fluoroscopy dose, and
the CL score also correlates with contrast utilization.
PMID- 27611919
TI - The use of whole thoracic ECG-gated MDCT for the de novo diagnosis of isolated
patent ductus arteriosus in middle aged or older subjects.
PMID- 27611920
TI - A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and
its active metabolites.
AB - AIM: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide
treatment for human African trypanosomiasis/sleeping sickness. Its main
metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2), show the
same in vitro pharmacological activity as FEX. METHODS & RESULTS: An LC-MS/MS
assay was developed for quantitation of FEX in DBS, collected via finger-prick
from healthy subjects. The DBS assay was specific, accurate and reproducible for
FEX, M1 and M2 when validated against the current plasma assay. DBS samples were
stable for 24 h at 37 degrees C with 95% relative humidity, and 58 weeks
desiccated at room temperature. CONCLUSION: DBS finger-prick sampling offers a
simple, practical method for determining FEX, M1 and M2 concentrations in
clinical studies in Africa.
PMID- 27611921
TI - lncRNA profiling in early-stage chronic lymphocytic leukemia identifies
transcriptional fingerprints with relevance in clinical outcome.
AB - Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA
molecules with an important emerging role in cancer. To elucidate their potential
pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and
clinically heterogeneous neoplasia, we investigated lncRNAs expression in a
prospective series of 217 early-stage Binet A CLL patients and 26 different
subpopulations of normal B-cells, through a custom annotation pipeline of
microarray data. Our study identified a 24-lncRNA-signature specifically
deregulated in CLL compared with the normal B-cell counterpart. Importantly, this
classifier was validated on an independent data set of CLL samples. Belonging to
the lncRNA signature characterizing distinct molecular CLL subgroups, we
identified lncRNAs recurrently associated with adverse prognostic markers, such
as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1
mutations. In addition, correlation analyses predicted a putative lncRNAs
interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA
independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able
to distinguish three different prognostic groups in our series of early-stage
patients. Overall, our study provides an important resource for future studies on
the functions of lncRNAs in CLL, and contributes to the discovery of novel
molecular markers with clinical relevance associated with the disease.
PMID- 27611924
TI - Pop Up: A new model of paediatric palliative care.
PMID- 27611923
TI - The influence of statins on osseointegration: a systematic review of animal model
studies.
AB - Recent research data have suggested that the beneficial action of statins in bone
tissue could improve osseointegration around titanium implants by increasing the
bone implant contact (BIC), the expression of bone morphogenetic protein-2 (BMP
2) and vascular endothelial growth factor (VEGF). The aim of this systematic
review was to evaluate the influence of statins on osseointegration of titanium
implants in animal studies. Two reviewers searched independently four databases
(MEDLINE, SCOPUS, WEB OF SCIENCE and the Cochrane Library), until March 15, 2016.
The Cochrane Collaboration's Tool for Assessing Risk of Bias was used to assess
the quality of the included studies. Papers that reported outcome data
considering bone implant contact (BIC), mechanical tests or other histological
evaluation were eligible for inclusion. 312 references were eletronically
retrieved, 21 full-text papers were screened and 17 studies were included.
Thirteen trials presented histomorphometry data on bone implant contact measures.
All of them showed a significant improved BIC when using statins. Despite data
from included studies point to beneficial effects, standardized studies and with
less risk of bias, are needed to clarify the role of statins on osseointegration.
PMID- 27611925
TI - Buddhism-as-a-meaning-system for coping with late-life stress: a conceptual
framework.
AB - OBJECTIVES: Religion is increasingly conceptualized as a meaning system for
adjustment and coping. Most of the conceptualizations are grounded in the Judeo
Christian tradition. They may thus not be applicable to Buddhism, which provides
a distinct tenor of meaning for coping. This article seeks to construct a
conceptual framework of Buddhism-as-a-meaning-system for coping with late-life
stress. METHOD: Literature review and conceptualization were employed. RESULTS:
Under this framework, Buddhism functions as a meaning system involving
existential meaning, cognitive meaning, and behavioral meaning. CONCLUSION: There
is reason to believe that this framework promises to offer a holistic conceptual
map of Buddhist coping in late life. Thus, it could serve as a guide for further
empirical and theoretical exploration in the uncharted terrains of Buddhist
coping in old age. In addition, gerontological practitioners could use this
framework as a frame of reference when working with elderly Buddhist clients who
are in stressful circumstances.
PMID- 27611922
TI - Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing
normal progenitors.
AB - The vast majority of patients with acute myeloid leukemia (AML) achieve complete
remission (CR) after standard induction chemotherapy. However, the majority
subsequently relapse and die of the disease. A leukemia stem cell (LSC) paradigm
has been invoked to explain this failure of CR to reliably translate into cure.
Indeed, LSCs are highly enriched in CD34+CD38- leukemic cells that exhibit
positive aldehyde dehydrogenase activity (ALDH+) on flow cytometry, these LSCs
are resistant to currently existing treatments in AML such as cytarabine and
anthracycline that, at the cost of great toxicity on normal cells, are highly
active against the leukemic bulk, but spare the LSCs responsible for relapse. To
try to combat the LSC population selectively, a well-characterized ALDH inhibitor
by the trivial name of dimethyl ampal thiolester (DIMATE) was assessed on sorted
CD34+CD38- subpopulations from AML patients and healthy patients. ALDH activity
and cell viability were monitored by flow cytometry. From enzyme kinetic studies
DIMATE is an active enzyme-dependent, competitive, irreversible inhibitor of
ALDH1. On cells in culture, DIMATE is a powerful inhibitor of ALDHs 1 and 3, has
a major cytotoxic activity on human AML cell lines. Moreover, DIMATE is highly
active against leukemic populations enriched in LSCs, but, unlike conventional
chemotherapy, DIMATE is not toxic for healthy hematopoietic stem cells which
retained, after treatment, their self-renewing and multi-lineage differentiation
capacity in immunodeficient mice, xenografted with human leukemic cells. DIMATE
eradicates specifically human AML cells and spares healthy mouse hematologic
cells.
PMID- 27611927
TI - Sex Differences in Visual Pathways: A Comment on Handa and McGivern (2015).
PMID- 27611926
TI - The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like
Behaviors in Juvenile Rats.
AB - OBJECTIVE: The aim of this study was to investigate depression-like behaviors of
juvenile rats with congenital and postnatal hypothyroidism. METHODS: Twenty-seven
newborn rat pups were used. First, 6-month-old Wistar Albino female rats were
impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day
of pregnancy until postnatal 21 days (P21) to generate pups with congenital
hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10),
methimazole was given from P0 to P21. In the control group (n=9), dam rats were
fed ad libitum and normal tap water. Offspring were fed with breast milk from
their mothers. The behavioral parameters were measured with the juvenile forced
swimming test (JFST). The procedure of JFST consisted of two sessions in two
consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2.
RESULTS: Increased immobility and decreased climbing duration were observed in
both congenital and postnatal hypothyroidism groups. Decreased swimming duration
was detected in the postnatal hypothyroidism group. Both hypothyroidism groups
had a lower body weight gain compared with the control group, while the
congenital hypothyroidism group had the lowest body weight. CONCLUSION: Our
results showed that hypothyroidism had negative effects on depression-like
behavior as well as on growth and development. Both congenital and postnatal
hypothyroidism caused an increase in immobility time in JFST. New studies are
required to understand the differing results on depression-like behavior between
congenital and postnatal hypothyroidism.
PMID- 27611928
TI - Surgery for Lumbar Spinal Stenosis in Individuals Aged 80 and Older: A
Multicenter Observational Study.
AB - OBJECTIVES: To compare clinical outcomes after decompressive surgery for central
lumbar spinal stenosis (LSS) in individuals aged 80 and older with those of
individuals aged 18-79. DESIGN: Prospective data from the Norwegian Registry for
Spine Surgery. SETTING: Multicenter observational study. PARTICIPANTS:
Individuals with central LSS undergoing surgery at 36 orthopedic or neurosurgical
departments (N = 1,503; 1,325 aged <80 (median 66, range 21-79); 178 aged >=80
(median 82, range 80-95)). INTERVENTION: Laminectomy or microdecompression.
MEASUREMENTS: Changes in Oswestry Disability Index (ODI), EuroQol 5D (EQ-5D),
back pain numerical rating scale (NRS), and leg pain NRS at 1 year. Complications
and duration of surgical procedures and hospital stays are reported. RESULTS: For
all participants, there was a significant improvement in ODI (difference 16.60
points, 95% confidence interval (CI) = 15.59-17.61, P < .001). There were no
differences between age cohorts in mean changes in ODI (0.2, 95% CI = -3.05-3.39,
P = .92), EQ-5D (0.02, 95% CI = -0.04-0.09, P = .49), back pain NRS (-0.2, 95% CI
= -0.7-0.4, P = .56), or leg pain NRS (-0.1, 95% CI = -0.7-0.5), P = .77). There
were no differences in perioperative complications between age cohorts (4.9% vs
7.9%, P = .11). Participants aged 80 and older reported more complications
occurring within 3 months (11.8% vs 7.5%, P = .02), mainly because of more
urinary tract infections (9.6% vs 3.5%, P = .001). Mean duration of hospital
stays was 1.3 days longer for participants aged 80 and (4.5 vs 3.2 days, P <
.001). There were no differences in duration of single-level microdecompression
(P = .94), two-level microdecompression (P = .53), single-level laminectomy (P =
.78), or two-level laminectomy (P = .08). CONCLUSION: Individuals aged 80 and
older experience improvement in self-reported outcomes similar to those of
younger individuals after decompressive surgery for LSS.
PMID- 27611929
TI - Early auditory processing in musicians and dancers during a contemporary dance
piece.
AB - The neural responses to simple tones and short sound sequences have been studied
extensively. However, in reality the sounds surrounding us are spectrally and
temporally complex, dynamic and overlapping. Thus, research using natural sounds
is crucial in understanding the operation of the brain in its natural
environment. Music is an excellent example of natural stimulation which, in
addition to sensory responses, elicits vast cognitive and emotional processes in
the brain. Here we show that the preattentive P50 response evoked by rapid
increases in timbral brightness during continuous music is enhanced in dancers
when compared to musicians and laymen. In dance, fast changes in brightness are
often emphasized with a significant change in movement. In addition, the auditory
N100 and P200 responses are suppressed and sped up in dancers, musicians and
laymen when music is accompanied with a dance choreography. These results were
obtained with a novel event-related potential (ERP) method for natural music.
They suggest that we can begin studying the brain with long pieces of natural
music using the ERP method of electroencephalography (EEG) as has already been
done with functional magnetic resonance (fMRI), these two brain imaging methods
complementing each other.
PMID- 27611930
TI - Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.
AB - The ability of a genotype to show diverse phenotypes in different environments is
called phenotypic plasticity. Phenotypic plasticity helps populations to evade
extinctions in novel environments, facilitates adaptation and fuels evolution.
However, most studies focus on understanding the genetic basis of phenotypic
regulation in specific environments. As a result, while it's evolutionary
relevance is well established, genetic mechanisms regulating phenotypic
plasticity and their overlap with the environment specific regulators is not well
understood. Saccharomyces cerevisiae is highly sensitive to the environment,
which acts as not just external stimulus but also as signalling cue for this
unicellular, sessile organism. We used a previously published dataset of a
biparental yeast population grown in 34 diverse environments and mapped genetic
loci regulating variation in phenotypic plasticity, plasticity QTL, and compared
them with environment-specific QTL. Plasticity QTL is one whose one allele
exhibits high plasticity whereas the other shows a relatively canalised
behaviour. We mapped phenotypic plasticity using two parameters-environmental
variance, an environmental order-independent parameter and reaction norm (slope),
an environmental order-dependent parameter. Our results show a partial overlap
between pleiotropic QTL and plasticity QTL such that while some plasticity QTL
are also pleiotropic, others have a significant effect on phenotypic plasticity
without being significant in any environment independently. Furthermore, while
some plasticity QTL are revealed only in specific environmental orders, we
identify large effect plasticity QTL, which are order-independent such that
whatever the order of the environments, one allele is always plastic and the
other is canalised. Finally, we show that the environments can be divided into
two categories based on the phenotypic diversity of the population within them
and the two categories have differential regulators of phenotypic plasticity. Our
results highlight the importance of identifying genetic regulators of phenotypic
plasticity to comprehensively understand the genotype-phenotype map.
PMID- 27611932
TI - Exosomes secreted from human colon cancer cells influence the adhesion of
neighboring metastatic cells: Role of microRNA-210.
AB - Cancer-secreted exosomes influence tumor microenvironment and support cancer
growth and metastasis. MiR-210 is frequently up-regulated in colorectal cancer
tissues and correlates with metastatic disease. We investigated whether exosomes
are actively released by HCT-8 colon cancer cells, the role of exosomal miR-210
in the cross-talk between primary cancer cells and neighboring metastatic cells
and its contribution in regulating epithelial-mesenchymal transition (EMT) and
mesenchymal-epithelial transition (MET). After 7 d of culture, a subpopulation of
viable HCT-8 cells detached the monolayer and started to grow in suspension,
suggesting anoikis resistance and a metastatic potential. The expression of key
proteins of EMT revealed that these cells were E-cadherin negative and vimentin
positive further confirming their metastatic phenotype and the acquisition of
anoikis resistance. Metastatic cells, in the presence of adherently growing HCT
8, continued to grow in suspension whereas only if seeded in cell-free wells,
were able to adhere again and to form E-cadherin positive and vimentin negative
new colonies, suggesting the occurrence of MET. The chemosensitivity to 5
fluorouracil and to FOLFOX-like treatment of metastatic cells was significantly
diminished compared to adherent HCT-8 cells. Of note, adherent new colonies
undergoing MET, were insensitive to both chemotherapeutic strategies. Electron
microscopy analysis demonstrated that adherently growing HCT-8, actually secreted
exosomes and that exosomes in turn were taken up by metastatic cells. When
exosomes secreted by adherently growing HCT-8 were administered to metastatic
cells, MET was significantly inhibited. miR-210 was significantly upregulated in
exosomes compared to its intracellular levels in adherently growing HCT-8 cells
and correlated to anoikis resistance and EMT markers. Exosomes containing miR-210
might be considered as EMT promoting signals that preserve the local cancer
growth permissive milieu and also guide metastatic cells to free, new sites of
dissemination.
PMID- 27611931
TI - Characterization of the Mouse and Human Monoacylglycerol O-Acyltransferase 1
(Mogat1) Promoter in Human Kidney Proximal Tubule and Rat Liver Cells.
AB - Monoacylglycerol acyltransferase 1 (Mogat1) catalyzes the conversion of
monoacylglycerols (MAG) to diacylglycerols (DAG), the precursor of several
physiologically important lipids such as phosphatidylcholine,
phosphatidylethanolamine and triacylglycerol (TAG). Expression of Mogat1 is
tissue restricted and it is highly expressed in the kidney, stomach and adipose
tissue but minimally in the normal adult liver. To understand the transcriptional
regulation of Mogat1, we characterized the mouse and human Mogat1 promoters in
human kidney proximal tubule-2 (HK-2) cells. In-silico analysis revealed several
peroxisome proliferator response element (PPRE) binding sites in the promoters of
both human and mouse Mogat1. These sites responded to all three peroxisome
proliferator activated receptor (PPAR) isoforms such that their respective
agonist or antagonist activated or inhibited the expression of Mogat1. PPRE site
mutagenesis revealed that sites located at -592 and -2518 are very effective in
decreasing luciferase reporter gene activity. Chromatin immunoprecipitation
(ChIP) assay using PPARalpha antibody further confirmed the occupancy of these
sites by PPARalpha. While these assays revealed the core promoter elements
necessary for Mogat1 expression, there are additional elements required to
regulate its tissue specific expression. Chromosome conformation capture (3C)
assay revealed additional cis-elements located ~10-15 kb upstream which interact
with the core promoter. These chromosomal regions are responsive to both
PPARalpha agonist and antagonist.
PMID- 27611933
TI - Cancer stem cells: master gatekeepers and regulators of cancer growth and
metastasis Introduction.
PMID- 27611935
TI - Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment
resistance.
AB - Cancer stem cells (CSCs) are a class of pluripotent cells that have been observed
in most types of solid and hematologic cancers. CSCs have been shown in numerous
cancer models to be involved in tumor development, cell proliferation, and
metastatic dissemination, while possessing a capacity for sustained self-renewal.
CSCs, which typically represent a small proportion of total cells of a given
tumor, also exhibit resistance to chemotherapy and radiotherapy. Indeed, exposure
to these treatments may promote "stemness" in nonstem cancer cells, which may
explain why successful therapeutic reduction of tumor bulk will often fail to
produce clinical improvement. Acquisition of stemness involves epithelial
mesenchymal transition (EMT), in which epithelial cells are transformed into a
mesenchymal phenotype characterized by increased capacities for migration,
invasiveness, and resistance to apoptosis. EMT may also contribute to metastasis
by driving dissemination of mesenchymal CSCs to distant locations, whereupon the
CSCs revert to an epithelial phenotype to support metastatic tumor growth.
Several different approaches to treatment aimed at overcoming the intrinsic
resistance of CSCs to conventional therapies are currently being developed. These
include agents targeting tumorigenic pathways, such as JAK2/STAT3 and PI3K/mTOR,
and immunotherapies, including vaccines and natural killer cells employed to
induce a T cell response.
PMID- 27611936
TI - Cancer stem cells: A nuanced perspective.
PMID- 27611934
TI - Cancer stem cells: understanding tumor hierarchy and heterogeneity.
AB - Heterogeneity within and between tumors is a well-known phenomenon that greatly
complicates the diagnosis and treatment of cancer. A large body of research
indicates that heterogeneity develops through time as tumor-initiating stem
cells, also known as cancer stem cells (CSCs), evolve genetic or epigenetic
alterations that allow them to differentiate into multiple tumor cell types.
Similar to normal stem cells, CSCs can self-renew and possess long-term
repopulation potential. However, unlike normal stem cells, CSCs are not subject
to the usual controls that limit growth. Different models have been postulated to
explain the heterogeneity of tumors, but it is widely agreed that interactions
between tumor cells and their microenvironment create niches that promote CSC
properties and enable their survival. Within the microenvironment, CSC self
renewal, replication, and differentiation are postulated to produce a hierarchy
of cells constituting the tumor mass. Increased understanding of the factors that
create and contribute to tumor heterogeneity may support the design of therapies
that affect CSC function and their microenvironments.
PMID- 27611937
TI - Cancer stem cell signaling pathways.
AB - Tissue development and homeostasis are governed by the actions of stem cells.
Multipotent cells are capable of self-renewal during the course of one's
lifetime. The accurate and appropriate regulation of stem cell functions is
absolutely critical for normal biological activity. Several key developmental or
signaling pathways have been shown to play essential roles in this regulatory
capacity. Specifically, the Janus-activated kinase/signal transducer and
activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3
kinase/phosphatase and tensin homolog, and nuclear factor-kappaB signaling
pathways have all been shown experimentally to mediate various stem cell
properties, such as self-renewal, cell fate decisions, survival, proliferation,
and differentiation. Unsurprisingly, many of these crucial signaling pathways are
dysregulated in cancer. Growing evidence suggests that overactive or abnormal
signaling within and among these pathways may contribute to the survival of
cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells
capable of self-renewal, differentiation, and generation of serially
transplantable heterogeneous tumors of several types of cancer.
PMID- 27611940
TI - Addiction, Heroin-Assisted Treatment and the Idea of Abstinence: A reply to
Henden.
AB - In our previous article on the question whether heroin addicts are able to give
informed consent voluntarily to research on heroin-assisted treatment, we
criticized the ongoing bioethical discussion of a flawed conceptualization of
heroin addicts' options. As a participant in this discussion, Edmund Henden
defends the conceptualization as sufficient for determining whether heroin
addicts are able to give informed consent to the research on heroin-assisted
treatment voluntarily. This discussion on research on heroin-assisted treatment
seems to go astray in several respects. In his reply to our article Henden
maintains some of the biases, such as the necessity of abstinence in recovery,
that seem to prevail in addiction research on a more general level as well. These
biases run the danger of having implausible ethical implications on stakeholders
in addiction research and treatment. In our reply to him, we will further clarify
and discuss the importance of describing the relevant issues in plausible terms
that do justice to the realities of the cases of informed consent in research on
heroin-assisted treatment and also raise a wider issue of the ethics of wording
as well as of the narrow scope, or 'tunnel vision', in addiction research as
currently conducted.
PMID- 27611938
TI - Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early
Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature
Mortality.
AB - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a
polyglutamine-repeat expansion in the huntingtin protein. Activation of the
kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of
HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to
kynurenine, the first step in this pathway. The prevalent, neuroinvasive
protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent
life-long infection in immune-competent individuals. T. gondii infection results
in activation of IDO which provides some protection against the parasite by
depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway
may therefore represent a point of synergism between HD and T. gondii infection.
We show here that IDO activity is elevated at least four-fold in frontal cortex
and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early
advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO
activity in HD mice. HD-infected mice died significantly earlier than wild-type
infected and HD control mice. Prior to death, infected HD mice demonstrated
decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild
type infected mice. We demonstrate for the first time that HD mice have an
altered response to an infectious agent that is characterized by premature
mortality, altered immune responses and early activation of IDO. Findings are
relevant to understanding how T. gondii infection may interact with pathways
mediating neurodegeneration in HD.
PMID- 27611939
TI - Detection of African Swine Fever Virus Antibodies in Serum and Oral Fluid
Specimens Using a Recombinant Protein 30 (p30) Dual Matrix Indirect ELISA.
AB - In the absence of effective vaccine(s), control of African swine fever caused by
African swine fever virus (ASFV) must be based on early, efficient, cost
effective detection and strict control and elimination strategies. For this
purpose, we developed an indirect ELISA capable of detecting ASFV antibodies in
either serum or oral fluid specimens. The recombinant protein used in the ELISA
was selected by comparing the early serum antibody response of ASFV-infected pigs
(NHV-p68 isolate) to three major recombinant polypeptides (p30, p54, p72) using a
multiplex fluorescent microbead-based immunoassay (FMIA). Non-hazardous (non
infectious) antibody-positive serum for use as plate positive controls and for
the calculation of sample-to-positive (S:P) ratios was produced by inoculating
pigs with a replicon particle (RP) vaccine expressing the ASFV p30 gene. The
optimized ELISA detected anti-p30 antibodies in serum and/or oral fluid samples
from pigs inoculated with ASFV under experimental conditions beginning 8 to 12
days post inoculation. Tests on serum (n = 200) and oral fluid (n = 200) field
samples from an ASFV-free population demonstrated that the assay was highly
diagnostically specific. The convenience and diagnostic utility of oral fluid
sampling combined with the flexibility to test either serum or oral fluid on the
same platform suggests that this assay will be highly useful under the conditions
for which OIE recommends ASFV antibody surveillance, i.e., in ASFV-endemic areas
and for the detection of infections with ASFV isolates of low virulence.
PMID- 27611941
TI - NTS/NTR1 co-expression enhances epithelial-to-mesenchymal transition and promotes
tumor metastasis by activating the Wnt/beta-catenin signaling pathway in
hepatocellular carcinoma.
AB - Neurotensin (NTS) is a neuropeptide distributed in central nervous and digestive
systems. In this study, the significant association between ectopic NTS
expression and tumor invasion was confirmed in hepatocellular carcinoma (HCC). In
primary HCC tissues, the NTS and neurotensin receptor 1 (NTR1) co-expression
(NTS+NTR1+) is a poor prognostic factor correlated with aggressive biological
behaviors and poor clinical prognosis. Enhanced epithelial-to-mesenchymal
transition (EMT) features, including decreased E-cadherin, increased beta-catenin
translocation and N-cadherin expression, were identified in NTS+NTR1+ HCC
tissues. Varied NTS-responsible HCC cell lines were established using NTR1
genetically modified Hep3B and HepG2 cells which were used to elucidate the
molecular mechanisms regulating NTS-induced EMT and tumor invasion in vitro.
Results revealed that inducing exogenous NTS stimulation and enhancing NTR1
expression promoted tumor invasion rather than proliferation by accelerating EMT
in HCC cells. The NTS-induced EMT was correlated with the remarkable increase in
Wnt1, Wnt3, Wnt5, Axin, and p-GSK3beta expression and was significantly reversed
by blocking the NTS signaling via the NTR1 antagonist SR48692 or by inhibiting
the activation of the Wnt/beta-catenin pathway via specific inhibitors, such as
TSW119 and DKK-1. SR48692 also inhibited the metastases of NTR1-overexpressing
HCC xenografts in the lungs in vivo. This finding implied that NTS may be an
important stimulus to promote HCC invasion and metastasis both in vitro and in
vivo, and NTS signaling enhanced the tumor EMT and invasion potentials by
activating the canonical Wnt/beta-catenin signaling pathway. Therefore, NTS may
be a valuable therapeutic target to prevent tumor progression in HCC.
PMID- 27611942
TI - Oncogenic activation of FAK drives apoptosis suppression in a 3D-culture model of
breast cancer initiation.
AB - A key hallmark of cancer cells is the loss of positional control over growth and
survival. Focal adhesion kinase (FAK) is a tyrosine kinase localised at sites of
integrin-mediated cell adhesion to the extracellular matrix. FAK controls a
number of adhesion-dependent cellular functions, including migration,
proliferation and survival. Although FAK is overexpressed and activated in
metastatic tumours, where it promotes invasion, it can also be elevated in
cancers that have yet to become invasive. The contribution of FAK to the early
stages of tumourigenesis is not known. We have examined the effect of activating
FAK in non-transformed mammary epithelial cells (MECs) to understand its role in
tumour initiation. In agreement with previous studies, we find FAK activation in
2D-culture promotes proliferation, migration, and epithelial-to-mesenchymal
transition. However in 3D-cultures that better resemble normal tissue morphology,
mammary cells largely respond to FAK activation via suppression of apoptosis,
promoting aberrant acinar morphogenesis. This is an acquired function of FAK,
because endogenous FAK signalling is not required for normal morphogenesis in 3D
culture or in vivo. Thus, FAK activation may facilitate tumour initiation by
causing resistance to apoptosis. We suggest that aberrant FAK activation in
breast epithelia is dependent upon the tissue context in which it occurs.
PMID- 27611944
TI - MicroRNA-126 inhibits tumor proliferation and angiogenesis of hepatocellular
carcinoma by down-regulating EGFL7 expression.
AB - This study aims to explore the effects of microRNA-126 (miR-126) on tumor
proliferation and angiogenesis of hepatocellular carcinoma (HCC) by targeting
EGFL7. HCC tissues and adjacent normal tissues were obtained from 71 HCC
patients. Immunohistochemistry (IHC) was conducted to detect expressions of EGFL7
and VEGF and the micro-vessel density (MVD). HCC cell lines were collected and
assigned into the blank, miR-126 mimics, miR-126 inhibitors, miR-126 mimics
negative control (NC), miR-126 inhibitors NC, si-EGFL7, and miR-126 inhibitors +
si-EGFL7 groups. Expressions of miR-126 and EGFL7 mRNA were detected by qRT-PCR
assay. The protein expressions of EGFL7 and VEGF were measured by Western
blotting. MTT assay was used to measure the proliferation of HCC cells. Tumor
xenograft model in nude mice was utilized to evaluate the influence of miR-126 on
tumor growth. HCC tissues had higher miR-126 expression and lower EGFL7 mRNA
expression than adjacent normal tissues. Compared with the blank, miR-126 mimic
NC, miR-126 inhibitor NC and miR-126 inhibitors + si-EGFL7 groups, the protein
expressions of EGFL7 and VEGF and cell proliferation were reduced in the miR-126
mimics and si-EGFL7 groups, while the opposite trend was found in the miR-126
inhibitors group. Compared with the blank and miR-126 inhibitors + siRNA-EGFL7
groups, tumor size, tumor weight, and MVD of transplanted tumors in nude mice
were significantly reduced in the miR-126 mimics and siRNA-EGFL7 groups, while
the opposite trend was found in the miR-126 inhibitors group. In conclusion, miR
126 could inhibit tumor proliferation and angiogenesis of HCC by down-regulating
EGFL7 expression.
PMID- 27611943
TI - Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21
regulates epidermal growth factor receptor in prostate cancer.
AB - Genomic loss of chromosome (chr) 8p21 region, containing prostate-specific NKX3.1
gene, is a frequent alteration of the prostate cancer (PCa) oncogenome. We
propose a novel, paradigm shifting hypothesis that this frequently deleted locus
is also associated with a cluster of microRNA genes- miR-3622a/b- that are lost
in PCa and play an important mechanistic role in progression and metastasis. In
this study, we demonstrate the role of miR-3622b in prostate cancer. Expression
analyses in a cohort of PCa clinical specimens and cell lines show that miR-3622b
expression is frequently lost in prostate cancer. Low miR-3622b expression was
found to be associated with tumor progression and poor biochemical recurrence
free survival. Further, our analyses suggest that miR-3622b expression is a
promising prostate cancer diagnostic biomarker that exhibits 100% specificity and
66% sensitivity. Restoration of miR-3622b expression in PCa cell lines led to
reduced cellular viability, proliferation, invasiveness, migration and increased
apoptosis. miR-3622b overexpression in vivo induced regression of established
prostate tumor xenografts pointing to its therapeutic potential. Further, we
found that miR-3622b directly represses Epidermal Growth Factor Receptor (EGFR).
In conclusion, our study suggests that miR-3622b plays a tumor suppressive role
and is frequently downregulated in prostate cancer, leading to EGFR upregulation.
Importantly, miR-3622b has associated diagnostic, prognostic and therapeutic
potential. Considering the association of chr8p21 loss with poor prognosis, our
findings are highly significant and support a novel concept that associates a
long standing observation of frequent loss of a chromosomal region with a novel
miRNA in prostate cancer.
PMID- 27611945
TI - Androgen receptor differentially regulates the proliferation of prostatic
epithelial cells in vitro and in vivo.
AB - Androgens regulate the proliferation and differentiation of prostatic epithelial
cells, including prostate cancer (PCa) cells in a context-dependent manner.
Androgens and androgen receptor (AR) do not invariably promote cell
proliferation; in the normal adult, endogenous stromal and epithelial AR
activation maintains differentiation and inhibits organ growth. In the current
study, we report that activation of AR differentially regulates the proliferation
of human prostate epithelial progenitor cells, NHPrE1, in vitro and in vivo.
Inducing AR signaling in NHPrE1 cells suppressed cell proliferation in vitro,
concomitant with a reduction in MYC expression. However, ectopic expression of AR
in vivo stimulated cell proliferation and induced development of invasive PCa in
tissue recombinants consisting of NHPrE1/AR cells and rat urogenital mesenchymal
(UGM) cells, engrafted under renal capsule of adult male athymic mice. Expression
of MYC increased in the NHPrE1/AR recombinant tissues, in contrast to the
reduction seen in vitro. The inhibitory effect of AR signaling on cell
proliferation in vitro were reduced by co-culturing NHPrE1/AR epithelial cells
with prostatic stromal cells. In conclusion, these studies revealed that AR
signaling differentially regulates proliferation of human prostatic epithelia
cells in vitro and in vivo through mechanisms involving stromal/epithelial
interactions.
PMID- 27611946
TI - Acquired resistance to BRAF inhibition in BRAFV600E mutant gliomas.
AB - Activating mutation of BRAF is a common finding in pediatric gliomas. As many as
14% of high grade and up to 66% of certain subtypes of low grade pediatric glioma
have the BRAFV600E mutation. Small molecule inhibitors that selectively target
BRAFV600E are FDA approved for melanoma and have shown significant efficacy in
treating BRAFV600E glioma in pre-clinical trials. Despite showing initial anti
tumor activity, acquired drug resistance significantly limits the benefit from
being treated with BRAFV600E inhibitors. Here, we have identified molecular
responses to BRAFV600E inhibitor treatment in human glioma models that have
substantial clinical implications. Specifically, we show that BRAFV600E inhibitor
resistant cells upregulate pro-survival mediators such as Wnt, and additionally
increase receptor tyrosine kinase activity, including EGFR and Axl, promoting
resistance to BRAFV600E inhibition. Our results suggest strategies to circumvent
acquired resistance to BRAFV600E inhibitor therapy, and thereby improve outcomes
for patients with BRAFV600E gliomas.
PMID- 27611947
TI - Detection of multiple mutations in urinary exfoliated cells from male bladder
cancer patients at diagnosis and during follow-up.
AB - Most bladder cancer (BC) patients need life-long, invasive and expensive
monitoring and treatment, making it a serious burden on the health system. Thus,
there is a pressing need for an accurate test to assist diagnosis and
surveillance of BC as an alternative to cystoscopy. Mutations in human TERT,
FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in
bladder tumor. Their concomitant presence in urine samples has not been fully
explored.We investigated a panel of mutations in DNA from exfoliated urinary
cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3,
PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome.
In 81 of these patients under surveillance, the same set of mutations was
screened in additional 324 samples prospectively collected.The most common
mutations detected in urine at diagnosis were in the TERT promoter. In non
invasive BC, these mutations were related to high risk and grade (p<0.0001) as
well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations
were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05).
Stronger associations were observed for combined TERT and FGFR3 mutations and
number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area
under the curve for combinations of mutations detected at diagnosis and follow-up
showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71
0.89).Mutations in urine of BC patients may represent reliable biomarkers. In
particular, TERT and FGFR3 mutations have a good accuracy of recurrence
prediction.
PMID- 27611948
TI - Zinc transporters are differentially expressed in human non-small cell lung
cancer.
AB - Lung cancer is one of the most common human malignancies worldwide, but its
oncogenesis process remains unclear. Recent studies demonstrated that zinc (Zn)
and Zn transporters were associated with the development and progression of human
cancers. The role of Zn transporters including ZIPs and ZnTs in lung cancer,
however, has never been evaluated. Thus, we aimed to investigate the expression
levels of all human Zn transporters, including 14 ZIPs and 10 ZnTs, in eight
different lung cancer cell lines and paired human tumor tissues. We observed
great variations in ZIPs and ZnTs mRNA levels across cell lines and human lung
cancer specimens. ZIPs showed a tendency to be upregulated, while ZnTs exhibited
a downward expression trend. ZIP4 was overexpressed in six lung cancer cell lines
and 59% (26/44) of tumor tissues, which was consistent with results from lung
cancer datasets including TCGA database. Our results indicated that the
dysregulation of Zn transporters may contribute to lung tumorigenesis.
PMID- 27611950
TI - MicroRNA-21 promotes TGF-beta1-induced epithelial-mesenchymal transition in
gastric cancer through up-regulating PTEN expression.
AB - This study aimed to explore the effects of miR-21 and PTEN/Akt signaling pathway
on TGF-beta1-induced epithelial-mesenchymal transition (EMT) in gastric cancer
(GC). GC tissues and adjacent tissues were collected from 83 patients. The qRT
PCR assay was performed to detect miR-21 expression. The expressions of PTEN, Akt
and p-Akt were detected by immunohistochemistry. After 48 h of treatment with TGF
beta1 (10 ng/mL), the SGC-7901 and KATO-III cells were divided into the blank,
negative control (NC), miR-21 inhibitors, PTEN-siRNA and miR-21 inhibitors + PTEN
siRNA groups. EMT related factors and PTEN expressions were detected by qRT-PCR
assay and Western blotting. The scratch test was conducted to observe cell
migration. Xenograft tumor model in nude mice was used to evaluate the effects of
miR-21 on EMT of GC cells in vivo. In GC tissues, the expressions of miR-21, Akt
and p-Akt were up-regulated, while PTEN expression was down-regulated. Gene and
protein expressions of E-cadherin and PTEN in the miR-21 inhibitors group were
higher than the blank, NC, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups,
while the expressions of N-cadherin, beta-catenin, Vimentin and Slug in the miR
21 inhibitors group were lower than other groups. MiR-21 inhibitors significantly
inhibit cell migration and invasion in GC cell lines. In vivo xenograft
experiment revealed that miR-21 inhibitor inhibits the growth of transplanted
tumor through up-regulating E-cadherin and PTEN expressions and down-regulating
the expressions of N-cadherin, beta-catenin, Vimentin and Slug. These results
suggest that miR-21 could promote TGF-beta1-induced EMT in GC cells through up
regulating PTEN expression.
PMID- 27611949
TI - F5-peptide induces aspermatogenesis by disrupting organization of actin- and
microtubule-based cytoskeletons in the testis.
AB - During the release of sperm at spermiation, a biologically active F5-peptide,
which can disrupt the Sertoli cell tight junction (TJ) permeability barrier, is
produced at the site of the degenerating apical ES (ectoplasmic specialization).
This peptide coordinates the events of spermiation and blood-testis barrier (BTB)
remodeling at stage VIII of the epithelial cycle, creating a local apical ES-BTB
axis to coordinate cellular events across the epithelium. The mechanism(s) by
which F5-peptide perturbs BTB restructuring, and its involvement in apical ES
dynamics remain unknown. F5-peptide, besides perturbing BTB integrity, was shown
to induce germ cell release from the epithelium following its efficient in vivo
overexpression in the testis. Overexpression of F5-peptide caused disorganization
of actin- and microtubule (MT)-based cytoskeletons, mediated by altering the
spatiotemporal expression of actin binding/regulatory proteins in the
seminiferous epithelium. F5-peptide perturbed the ability of actin microfilaments
and/or MTs from converting between their bundled and unbundled/defragmented
configuration, thereby perturbing adhesion between spermatids and Sertoli cells.
Since apical ES and basal ES/BTB are interconnected through the underlying
cytoskeletal networks, this thus provides an efficient and novel mechanism to
coordinate different cellular events across the epithelium during spermatogenesis
through changes in the organization of actin microfilaments and MTs. These
findings also illustrate the potential of F5-peptide being a male contraceptive
peptide for men.
PMID- 27611951
TI - Aberrant expression of KPNA2 is associated with a poor prognosis and contributes
to OCT4 nuclear transportation in bladder cancer.
AB - Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a
number of cancers and associated with poor prognosis. Here, we found that
expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues
and significantly associated with primary tumor stage and bladder cancer
patients' poorer prognosis. Our data also showed decreased cell proliferation and
migration rates of bladder cancer cell lines when the expression of KPNA2 and
OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co
IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits
OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up
regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is
correlated with increased aggressive tumor behavior. Also, we propose that KPNA2
regulates the process of OCT4 nuclear transportation in bladder cancer.
PMID- 27611952
TI - Role of TP53 mutations in triple negative and HER2-positive breast cancer treated
with neoadjuvant anthracycline/taxane-based chemotherapy.
AB - BACKGROUND: TP53 mutations are frequent in breast cancer, however their clinical
relevance in terms of response to chemotherapy is controversial. METHODS: 450 pre
therapeutic, formalin-fixed, paraffin-embedded core biopsies from the phase II
neoadjuvant GeparSixto trial that included HER2-positive and triple negative
breast cancer (TNBC) were subjected to Sanger sequencing of exons 5-8 of the TP53
gene. TP53 status was correlated to response to neoadjuvant anthracycline/taxane
based chemotherapy with or without carboplatin and trastuzumab/lapatinib in HER2
positive and bevacizumab in TNBC. p53 protein expression was evaluated by
immunohistochemistry in the TNBC subgroup. RESULTS: Of 450 breast cancer samples
297 (66.0%) were TP53 mutant. Mutations were significantly more frequent in TNBC
(74.8%) compared to HER2-positive cancers (55.4%, P < 0.0001). Neither mutations
nor different mutation types and effects were associated with pCR neither in the
whole study group nor in molecular subtypes (P > 0.05 each). Missense mutations
tended to be associated with a better survival compared to all other types of
mutations in TNBC (P = 0.093) and in HER2-positive cancers (P = 0.071). In TNBC,
missense mutations were also linked to higher numbers of tumor-infiltrating
lymphocytes (TILs, P = 0.028). p53 protein overexpression was also linked with
imporved survival (P = 0.019). CONCLUSIONS: Our study confirms high TP53 mutation
rates in TNBC and HER2-positive breast cancer. Mutations did not predict the
response to an intense neoadjuvant chemotherapy in these two molecular breast
cancer subtypes.
PMID- 27611955
TI - Fact or friction: Examination of the transparency, reliability and sufficiency of
the ACE-V method of fingerprint analysis.
AB - Three studies are presented which provide a mixed methods exploration of
fingerprint analysis. Using a qualitative approach (Expt 1), expert analysts used
a 'think aloud' task to describe their process of analysis. Thematic analysis
indicated consistency of practice, and experts' comments underpinned the
development of a training tool for subsequent use. Following this, a quantitative
approach (Expt 2) assessed expert reliability on a fingerprint matching task. The
results suggested that performance was high and often at ceiling, regardless of
the length of experience held by the expert. As a final test, the experts'
fingerprint analysis method was taught to a set of naive students, and their
performance on the fingerprint matching task was compared both to the expert
group and to an untrained novice group (Expt 3). Results confirmed that the
trained students performed significantly better than the untrained students.
However, performance remained substantially below that of the experts. Several
explanations are explored to account for the performance gap between experts and
trained novices, and their implications are discussed in terms of the future of
fingerprint evidence in court.
PMID- 27611953
TI - Clustered somatic mutations are frequent in transcription factor binding motifs
within proximal promoter regions in melanoma and other cutaneous malignancies.
AB - Most cancer DNA sequencing studies have prioritized recurrent non-synonymous
coding mutations in order to identify novel cancer-related mutations. Although
attention is increasingly being paid to mutations in non-coding regions, standard
approaches to identifying significant mutations may not be appropriate and there
has been limited analysis of mutational clusters in functionally annotated non
coding regions. We sought to identify clustered somatic mutations (hotspot
regions across samples) in functionally annotated regions in melanoma and other
cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma
and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent
clustered hotspot mutations in proximal promoters, with some specific clusters
present in up to 25% of cases. Mutations in melanoma were clustered within ETS
and Sp1 transcription factor binding motifs, had a UV signature and were
identified in other cutaneous malignancies. Clinicopathologic correlation and
mutation analysis support a causal role for chronic UV irradiation generating
somatic mutations in transcription factor binding motifs of proximal promoters.
PMID- 27611954
TI - Development of the green bottle fly Lucilia illustris at constant temperatures.
AB - Lucilia illustris (Meigen 1826) (Diptera: Calliphoridae) is a cosmopolitan
species that commonly colonizes carcasses and occasionally acts as parasites of
humans or livestock, making it an insect of significant importance in forensic,
medical, and veterinary entomology. However, only a few studies have documented
the development of L. illustris. Here, we studied the developmental duration and
larval body length changes of L. illustris under nine constant temperatures
ranging from 15.0 to 35.0 degrees C. Using these results, we generated an
isomorphen diagram, thermal summation model, and isomegalen diagram for L.
illustris. Simulation equations of the variation in the larval body length with
time after hatching and variation in time after hatching with the body length
were also obtained. L. illustris could complete its life cycle in 15.0-32.5
degrees C, while its development was incomplete at 35.0 degrees C, where the
pupae failed to transform into adults. The development duration was 955.5+/-16.9,
625.7+/-16.9, 509.3+/-18.3, 410.0+/-17.0, 346.7+/-12.2, 290.2+/-6.7, 257.1+/-8.9,
and 234.8+/-3.2h at 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, and 32.5 degrees C,
respectively. The developmental threshold temperature and thermal constant were
9.30+/-0.19 degrees C and 5367.2+/-98.3 degrees Ch, respectively. These results
provide an important basis for the use of L. illustris development-based
estimation of the minimum postmortem interval (PMImin) in forensic entomology.
PMID- 27611956
TI - Detection of the diuretic hydrochlorothiazide in a doping control urine sample as
the result of a non-steroidal anti-inflammatory drug (NSAID) tablet
contamination.
AB - Hydrochlorothiazide (HCTZ, 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7
sulfonamide-1,1-dioxide) belongs to the class of diuretic agents that represent
one of today's cornerstones of the treatment of hypertensive patients. In
addition to its clinical relevance, HCTZ is prohibited in sports according to the
regulations of the World Anti-Doping Agency (WADA) at all times and has
frequently been detected in sports drug testing urine samples worldwide since its
ban was introduced in 1988. Despite these facts, the adverse analytical finding
concerning HCTZ in an in-competition routine doping control sample collected in
December 2014 was further investigated, particularly motivated by the comparably
low urinary concentration of the drug accounting for approximately 5ng/mL. The
athlete in question did not declare the use of any nutritional supplement or
medication other than the ingestion of a non-steroidal anti-inflammatory drug
(NSAID) prior to competition. Hence, the drug (formulated as coated tablet)
provided by the athlete as well as the corresponding retention sample of the
manufacturer were analyzed. Noteworthy, both samples confirmed the presence of
about 2MUg of HCTZ per tablet. In order to further probe for the plausibility of
the observed urinary HCTZ concentrations with the scenario of drug ingestion and
subsequent doping control sample collection, administration studies with produced
HCTZ-spiked placebo-tablets (2.5MUg of HCTZ/tablet) were conducted. Urine
specimens were collected prior to and after ingestion of the drug and subjected
to routine doping control analytical procedures employing liquid
chromatography/tandem mass spectrometry. While blank urine samples returned
negative test results, post-administration specimens were found to contain HCTZ
at concentrations of approximately 1-16ng/mL, which supported the athlete's
inadvertent intake of HCTZ via contaminated NSAID tablets. Due to the substantial
sensitivity of test methods employed today by doping control laboratories, even
drug contaminations ranging within the good manufacturing practice (GMP) limit of
10ppm overall carry-over can evidently lead to adverse analytical findings. This
calls into question whether selected (classes of) substances such as diuretics
should be reported only when exceeding a defined reporting level and/or whether
adverse analytical findings of non-threshold substances should be reported with
an estimated semi-quantitative concentration of the identified substance to
facilitate the result management by anti-doping organizations.
PMID- 27611957
TI - Buying drugs on a Darknet market: A better deal? Studying the online illicit drug
market through the analysis of digital, physical and chemical data.
AB - Darknet markets, also known as cryptomarkets, are websites located on the Darknet
and designed to allow the trafficking of illicit products, mainly drugs. This
study aims at presenting the added value of combining digital, chemical and
physical information to reconstruct sellers' activities. In particular, this
research focuses on Evolution, one of the most popular cryptomarkets active from
January 2014 to March 2015. Evolution source code files were analysed using
Python scripts based on regular expressions to extract information about listings
(i.e., sales proposals) and sellers. The results revealed more than 48,000
listings and around 2700 vendors claiming to send illicit drug products from 70
countries. The most frequent categories of illicit drugs offered by vendors were
cannabis-related products (around 25%) followed by ecstasy (MDA, MDMA) and
stimulants (cocaine, speed). The cryptomarket was then especially studied from a
Swiss point of view. Illicit drugs were purchased from three sellers located in
Switzerland. The purchases were carried out to confront digital information
(e.g., the type of drug, the purity, the shipping country and the concealment
methods mentioned on listings) with the physical analysis of the shipment
packaging and the chemical analysis of the received product (purity, cutting
agents, chemical profile based on minor and major alkaloids, chemical class). The
results show that digital information, such as concealment methods and shipping
country, seems accurate. But the illicit drugs purity is found to be different
from the information indicated on their respective listings. Moreover, chemical
profiling highlighted links between cocaine sold online and specimens seized in
Western Switzerland. This study highlights that (1) the forensic analysis of the
received products allows the evaluation of the accuracy of digital data collected
on the website, and (2) the information from digital and physical/chemical traces
are complementary to evaluate the practices of the online selling of illicit
drugs on cryptomarkets.
PMID- 27611958
TI - Mobile app for treatment of stress urinary incontinence: A randomized controlled
trial.
AB - AIMS: To evaluate the effect of a mobile app treatment for stress urinary
incontinence (SUI) in women. METHODS: Randomized controlled trial, conducted 2013
2014 in Sweden. Community-dwelling adult women with >=1 SUI episode/week
recruited through our website and randomized to app treatment (n = 62) or control
group (postponed treatment, n = 61). One participant from each group was lost to
follow-up. Intervention was the mobile app Tat(r) with a treatment program
focused on pelvic floor muscle training (PFMT), and information about SUI and
lifestyle factors. Primary outcomes, 3 months after randomization: symptom
severity (International Consultation on Incontinence Modular Questionnaire
Urinary Incontinence Short Form [ICIQ-UI SF]); and condition-specific quality of
life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). RESULTS:
One hundred and twenty-three women were included (mean age 44.7), with
moderate/severe SUI (97.5%, 120/123), mean ICIQ-UI SF score 11.1 (SD 2.8) and
mean ICIQ-LUTSqol score 34.4 (SD 6.1) at baseline. At follow-up, the app group
reported improvements in symptom severity (mean ICIQ-UI SF score reduction: 3.9,
95% confidence interval 3.0-4.7) and condition-specific quality of life (mean
ICIQ-LUTSqol score reduction: 4.8, 3.4-6.2) and the groups were significantly
different (mean ICIQ-UI SF score difference: -3.2, -4.3to -2.1; mean ICIQ-LUTSqol
score difference: -4.6, -7.8 to -1.4). In the app group, 98.4% (60/61) performed
PFMT at follow-up, and 41.0% (25/61) performed it daily. CONCLUSIONS: The mobile
app treatment was effective for women with SUI and yielded clinically relevant
improvements. This app may increase access to first-line treatment and adherence
to PFMT.
PMID- 27611959
TI - Altered Resting-State Functional Connectivity of the Striatum in Parkinson's
Disease after Levodopa Administration.
AB - BACKGROUND: Despite improvement in motor symptoms, the effect of dopaminergic
medications on cognition in patients with Parkinson's disease (PD) is less clear.
The purpose of this study was to reveal levodopa-induced acute changes in the
functional connectivity of the striatum in patients with PD compared with matched
untreated patients and healthy volunteers. METHODS: Twenty-two patients with PD
underwent functional magnetic resonance imaging both ON and OFF dopamine
replacement therapy on two consecutive days. Twenty-eight normal aging volunteers
also did them without taking in levodopa. Three caudate seeds and two putamen
seeds were selected to calculate functional connectivity intensity. RESULTS:
Motor symptoms measured by UPDRS were significantly worse in PD OFF than PD ON.
Decreased functional connectivity in PD OFF compared to controls was detected in
the following seed regions: dorsal caudate, ventral putamen and dorsal putamen.
Increases in connectivity in PD ON compared to controls were found in the primary
and supplementary motor areas and the associative prefrontal and parietal
regions, while decreases in anterior cingulate, ventromedial prefrontal cortex,
and parahippocampal gyrus. For the ventral striatal seeds, decreased connectivity
in PD ON compared to PD OFF was found in the ventromedial prefrontal and
orbitofrontal regions, dorsolateral prefrontal regions. For the dorsal striatal
seeds, increased connectivity in PD ON compared to PD OFF was observed in the
primary and secondary motor areas. CONCLUSION: Our results suggest that levodopa
significantly changes the motor and cognitive networks of the cortico-striatal
pathways. This knowledge will lead clinicians to survey a broader range of
symptoms in determining optimal therapy.
PMID- 27611960
TI - McGurk illusion recalibrates subsequent auditory perception.
AB - Visual information can alter auditory perception. This is clearly illustrated by
the well-known McGurk illusion, where an auditory/aba/ and a visual /aga/ are
merged to the percept of 'ada'. It is less clear however whether such a change in
perception may recalibrate subsequent perception. Here we asked whether the
altered auditory perception due to the McGurk illusion affects subsequent
auditory perception, i.e. whether this process of fusion may cause a
recalibration of the auditory boundaries between phonemes. Participants
categorized auditory and audiovisual speech stimuli as /aba/, /ada/ or /aga/
while activity patterns in their auditory cortices were recorded using fMRI.
Interestingly, following a McGurk illusion, an auditory /aba/ was more often
misperceived as 'ada'. Furthermore, we observed a neural counterpart of this
recalibration in the early auditory cortex. When the auditory input /aba/ was
perceived as 'ada', activity patterns bore stronger resemblance to activity
patterns elicited by /ada/ sounds than when they were correctly perceived as
/aba/. Our results suggest that upon experiencing the McGurk illusion, the brain
shifts the neural representation of an /aba/ sound towards /ada/, culminating in
a recalibration in perception of subsequent auditory input.
PMID- 27611962
TI - 18F-FECH PET/CT to Assess Clinically Significant Disease in Prostate Cancer:
Correlation With Maximum and Total Cancer Core Length Obtained via MRI-Guided
Template Mapping Biopsies.
AB - OBJECTIVE: The objective of this study was to detect clinically significant and
insignificant prostate cancer on 18F-fluoroethylcholine (FECH) PET/CT and to
correlate findings with transperineal template-guided prostate mapping (TPM)
biopsy. SUBJECTS AND METHODS: Fifty-six lobes of the prostate were analyzed in 28
men who underwent FECH PET/CT and TPM. Whole-body images and pelvic images were
acquired at 60 and 90 minutes after tracer administration. FECH PET/CT findings
were correlated with TPM. Sensitivity, specificity, positive predictive values,
negative predictive values, and AUC of dual phase FECH PET/CT were calculated.
RESULTS: Mean age of the patients was 68.8 years (range, 53-79 years), and mean
prostate-specific antigen level was 12.1 ng/mL (range, 0.6-45 ng/mL). Mean
maximum cancer core length was 4.4 mm (median, 4 mm; range, 1-14 mm) and mean
total cancer core length, 14.6 mm (median, 14.6 mm; range, 1-82 mm). Prostate
cancer was identified in 38 lobes with a Gleason score of 6 in five lobes (13%),
7 in 27 lobes (71%), 8 in four lobes (11%), and 9 in two lobes (5%). FECH PET/CT
showed findings of prostate cancer in 46/56 lobes (82%). The ranges for maximum
standardized uptake value for 60- and 90-minute FECH PET/CT were 1.3-11.4 and 1.2
10.9, respectively. Clinically significant cancer was seen in 30 of 38 positive
lobes; eight had clinically insignificant disease. For 60-minute imaging, the
sensitivity, specificity, and ROC AUC were 75%, 75%, and 0.746 (95% CI, 0.612
0.853). For 90-minute imaging, the sensitivity, specificity, and ROC AUC were
73.7%, 58.3%, and 0.646 (95% CI, 0.498-0.776). Overall sensitivity, specificity,
positive predictive value, and negative predictive value were 95%, 50%, 82.6%,
and 80%, respectively. CONCLUSION: FECH PET/CT can detect prostate cancer and
localizes TPM biopsy-proven clinically significant prostate cancer with
sensitivity of greater than 89.7%. Of the two imaging durations, 60-minute
imaging is more sensitive and specific than 90-minute imaging.
PMID- 27611963
TI - Designing Industrial Networks Using Ecological Food Web Metrics.
AB - Biologically Inspired Design (biomimicry) and Industrial Ecology both look to
natural systems to enhance the sustainability and performance of engineered
products, systems and industries. Bioinspired design (BID) traditionally has
focused on a unit operation and single product level. In contrast, this paper
describes how principles of network organization derived from analysis of
ecosystem properties can be applied to industrial system networks. Specifically,
this paper examines the applicability of particular food web matrix properties as
design rules for economically and biologically sustainable industrial networks,
using an optimization model developed for a carpet recycling network. Carpet
recycling network designs based on traditional cost and emissions based
optimization are compared to designs obtained using optimizations based solely on
ecological food web metrics. The analysis suggests that networks optimized using
food web metrics also were superior from a traditional cost and emissions
perspective; correlations between optimization using ecological metrics and
traditional optimization ranged generally from 0.70 to 0.96, with flow-based
metrics being superior to structural parameters. Four structural food parameters
provided correlations nearly the same as that obtained using all structural
parameters, but individual structural parameters provided much less satisfactory
correlations. The analysis indicates that bioinspired design principles from
ecosystems can lead to both environmentally and economically sustainable
industrial resource networks, and represent guidelines for designing sustainable
industry networks.
PMID- 27611964
TI - Palladium-Catalyzed Ylidyl-Carbonylation of Aryl Halides To Produce alpha
Acylphosphoranes.
AB - An efficient synthesis of alpha-acylphosphoranes by palladium-catalyzed
carbonylation of aryl iodides with carbon monoxide and stabilized phosphonium
ylides has been developed. Featuring 44 examples, the protocol displayed a wide
substrate scope under mild reaction conditions, showcasing its potential in
synthetic organic chemistry.
PMID- 27611965
TI - A radio-odontometric analysis of sexual dimorphism in deciduous dentition.
AB - OBJECTIVE: It has been suggested that the level of sexual dimorphism in deciduous
dentition is relatively lower than that in permanent dentition. However, in sub
adult skeletal remains whose osseous morphological traits of the sex have not
defined yet, predicting sex on the basis of odontometric features may be the most
precise technique. The aim of the present study was to assess the degree of
sexual dimorphism in marginal enamel, dentin and pulp dimensions of second molar
deciduous teeth in a pediatric population. METHOD AND MATERIALS: The present
study was conducted on bitewing radiographs of 64 males and 60 females. The
greatest width of enamel, dentin and pulp on mandibular and maxillary second
molar deciduous teeth were measured. Student's t-test and discriminant analysis
were used to compare the differences in the odontometric parameters between
females and males. RESULTS: Among the second molar measurements, only the
maxillary pulp width did significantly discriminate the sex groups. The accuracy
of sex identification of a case based on deciduous second molar tooth was
approximately 68%. CONCLUSIONS: The application of second molar deciduous teeth
in sex prediction showed moderate level of sexual dimorphism. In this respect,
the maxillary pulp width had the greatest amount of contribution in sex
discrimination. Therefore, these odontometric traits, in conjunction with other
skeletal features, can be used as a supplementary sexing tool for gender
prediction in forensic anthropology.
PMID- 27611966
TI - Correlation between mtDNA complexity and mtDNA replication mode in developing
cotyledon mitochondria during mung bean seed germination.
AB - The currently accepted model of recombination-dependent replication (RDR) in
plant mitochondrial DNA (mtDNA) does not clearly explain how RDR progresses and
how highly complex mtDNA develops. This study aimed to investigate the
correlation between RDR and mtDNA complexity during mitochondrial development in
mung bean (Vigna radiata) seed, and the initiation and processing of RDR in plant
mitochondria. Flow cytometry, pulsed-field gel electrophoresis, electron
microscopy, real-time PCR and biochemical studies were used in this study. The
highly dynamic changes in mtDNA complexity correspond to mtDNA RDR activity
throughout mitochondrial development. With in vitro freeze-thaw treatment or
prolonged in vivo cold incubation, the mtDNA rosette core disappeared and the
rosette structure converted to a much longer linear DNA structure. D-loops,
Holliday junctions and putative RDR forks often appeared near the rosette cores.
We hypothesize that the rosette core may consist of condensed mtDNA and a
replication starting sequence, and play an initial and central role in RDR. The
satellite cores in the rosette structure may represent the re-initiation sites of
mtDNA RDR in the same parental molecule, thereby forming highly complex and giant
mitochondrial molecules, representing the RDR intermediates, in vivo.
PMID- 27611968
TI - The Nitrogenase FeMo-Cofactor Precursor Formed by NifB Protein: A Diamagnetic
Cluster Containing Eight Iron Atoms.
AB - The biological activation of N2 occurs at the FeMo-cofactor, a 7Fe-9S-Mo-C
homocitrate cluster. FeMo-cofactor formation involves assembly of a Fe6-8 -SX -C
core precursor, NifB-co, which occurs on the NifB protein. Characterization of
NifB-co in NifB is complicated by the dynamic nature of the assembly process and
the presence of a permanent [4Fe-4S] cluster associated with the radical SAM
chemistry for generating the central carbide. We have used the physiological
carrier protein, NifX, which has been proposed to bind NifB-co and deliver it to
the NifEN protein, upon which FeMo-cofactor assembly is ultimately completed.
Preparation of NifX in a fully NifB-co-loaded form provided an opportunity for
Mossbauer analysis of NifB-co. The results indicate that NifB-co is a diamagnetic
(S=0) 8-Fe cluster, containing two spectroscopically distinct Fe sites that
appear in a 3:1 ratio. DFT analysis of the (57) Fe electric hyperfine
interactions deduced from the Mossbauer analysis suggests that NifB-co is either
a 4Fe(2+) -4Fe(3+) or 6Fe(2+) -2Fe(3+) cluster having valence-delocalized states.
PMID- 27611969
TI - RNA-Seq Analysis Reveals a Negative Role of KLF16 in Adipogenesis.
AB - In this study, we performed high throughput RNA sequencing at the preadipocyte
(D0) and differentiated adipocyte (D7) stages of primary brown preadipocyte
differentiation in order to characterize the transcriptional events regulating
differentiation and function. Compared to the preadipocyte stage (D0), 6,668
genes were identified as differentially expressed genes (DEGs) with a fold change
of >= 2.0 at the differentiated adipocyte stage (D7). Several adipogenic genes
including peroxisome proliferator-activated receptor-gamma (PPARgamma) and
CCAAT/enhancer-binding protein-alpha (C/EBPalpha), and Kruppel-like factor (KLF)
family genes were differentially expressed at D0 and D7. Since KLF16 gene
expression was downregulated at day 7 and its adipogenic function has not been
characterized, we investigated its role in adipogenesis. Knockdown of KLF16
stimulated the differentiation of both brown and 3T3-L1 preadipocytes, and led to
increased PPARgamma expression. However, overexpression of KLF16 had opposite
effects. Furthermore, KLF16 downregulated PPARgamma expression in brown
adipocytes and inhibited its promoter activity. These results indicate that KLF16
inhibits adipogenesis through downregulation of PPARgamma expression.
PMID- 27611967
TI - Identification of Altered Metabolomic Profiles Following a Panchakarma-based
Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological
Transformation Initiative (SBTI).
AB - The effects of integrative medicine practices such as meditation and Ayurveda on
human physiology are not fully understood. The aim of this study was to identify
altered metabolomic profiles following an Ayurveda-based intervention. In the
experimental group, 65 healthy male and female subjects participated in a 6-day
Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet,
meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased
(adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to
control group (n = 54) after Bonferroni correction for multiple testing; within
these compounds, the phosphatidylcholine with the greatest decrease in abundance
was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional
57 metabolites that were differentially abundant between groups. Pathway analysis
suggests that the intervention results in changes in metabolites across many
pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein
metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma
induced modulation of metabotypes. Panchakarma promoted statistically significant
changes in plasma levels of phosphatidylcholines, sphingomyelins and others in
just 6 days. Forthcoming studies that integrate metabolomics with genomic,
microbiome and physiological parameters may facilitate a broader systems-level
understanding and mechanistic insights into these integrative practices that are
employed to promote health and well-being.
PMID- 27611971
TI - Different Ultimate Factors Define Timing of Breeding in Two Related Species.
AB - Correct reproductive timing is crucial for fitness. Breeding phenology even in
similar species can differ due to different selective pressures on the timing of
reproduction. These selection pressures define species' responses to warming
springs. The temporal match-mismatch hypothesis suggests that timing of breeding
in animals is selected to match with food availability (synchrony).
Alternatively, time-dependent breeding success (the date hypothesis) can result
from other seasonally deteriorating ecological conditions such as intra- or
interspecific competition or predation. We studied the effects of two ultimate
factors on the timing of breeding, synchrony and other time-dependent factors
(time-dependence), in sympatric populations of two related forest-dwelling
passerine species, the great tit (Parus major) and the willow tit (Poecile
montanus) by modelling recruitment with long-term capture-recapture data. We
hypothesized that these two factors have different relevance for fitness in these
species. We found that local recruitment in both species showed quadratic
relationships with both time-dependence and synchrony. However, the importance of
these factors was markedly different between the studied species. Caterpillar
food played a predominant role in predicting the timing of breeding of the great
tit. In contrast, for the willow tit time-dependence modelled as timing in
relation to conspecifics was more important for local recruitment than synchrony.
High caterpillar biomass experienced during the pre- and post-fledging periods
increased local recruitment of both species. These contrasting results confirm
that these species experience different selective pressures upon the timing of
breeding, and hence responses to climate change may differ. Detailed information
about life-history strategies is required to understand the effects of climate
change, even in closely related taxa. The temporal match-mismatch hypothesis
should be extended to consider subsequent critical periods when food needs to be
abundantly available.
PMID- 27611970
TI - Positional and Curvature Difference of Lamina Cribrosa According to the Baseline
Intraocular Pressure in Primary Open-Angle Glaucoma: A Swept-Source Optical
Coherence Tomography (SS-OCT) Study.
AB - PURPOSE: To investigate the variation of lamina cribrosa (LC) structure based on
the baseline intraocular pressure (IOP) in eyes with primary open-angle glaucoma
(POAG) and healthy individuals using swept-source optical coherence tomography.
METHODS: A total of 108 eyes with POAG and 61 healthy eyes were recruited. Based
on the baseline IOP, the POAG eyes were divided into higher-baseline IOP (HTG;
baseline IOP > 21 mmHg, n = 38 eyes) and lower-baseline IOP (NTG; baseline IOP <=
21 mmHg, n = 70 eyes). The anterior laminar insertion depth (ALID), mean LC depth
(mLCD), and the LC curvature index (mLCD-ALID) were measured, and compared among
the three groups. The regional variation of LC structure was evaluated by
vertical-horizontal ALID difference. RESULTS: The mLCD and LC curvature index
were greatest in HTG eyes (520.3 +/- 123.0 and 80.9 +/- 30.7 MUm), followed by
NTG (463.2 +/- 110.5 and 64.5 +/- 30.7 MUm) and healthy eyes (382.9 +/- 107.6 and
47.6 +/- 25.7 MUm, all P < 0.001). However, there were no significant difference
in ALID between HTG and NTG eyes. The vertical-horizontal ALID difference was
larger in NTG eyes (72.8 +/- 56.2 MUm) than in HTG (32.7 +/- 61.4 MUm, P = 0.004)
and healthy eyes (25.5 +/- 34.8 MUm, P < 0.001). CONCLUSIONS: Lamina cribrosa
position and curvature differed in POAG eyes with low and high IOP. This would
support the theory that IOP induced biomechanical effects on the optic play a
role on glaucoma.
PMID- 27611974
TI - treA Codifies for a Trehalase with Involvement in Xanthomonas citri subsp. citri
Pathogenicity.
AB - Citrus canker, caused by the bacterium Xanthomonas citri subsp. citri (Xcc), is a
severe disease of citrus. Xcc presents broad spectrum of citrus hosts including
economically important species whereas X. fuscans subsp. aurantifolii-type C
(XauC) causes a milder disease and only infects Citrus aurantifolia. Trehalase
catalyzes hydrolysis of the disaccharide trehalose, a sugar that has been
reported to be related to Xcc pathogenicity. We expressed the recombinant gene
product and assessed Xcc trehalase structural and kinetics data. The recombinant
protein presented 42.7% of secondary structures in alpha-helix and 13% in beta
sheets, no quaternary structure in solution, and Michaelis-Menten constant (KM)
of 0.077 mM and Vmax 55.308 MUMol glucose.min-1.mg protein-1 for trehalose. A Xcc
mutant strain (XccDeltatreA) was produced by gene deletion from Xcc genome.
Enzymatic activity of trehalase was determined in Xcc, XauC and XccDeltatreA
cellular lysates, showing the highest values for XauC in in vitro infective
condition and no activity for XccDeltatreA. Finally, leaves of Citrus
aurantifolia infected with XccDeltatreA showed much more drenching and necrosis
than those infected by wild type Xcc. We concluded that trehalase contributes to
alleviate bacterial virulence and that inability for trehalose hydrolysis may
promote higher Xcc infectivity.
PMID- 27611972
TI - Activation of Cannabinoid Receptor 2 Ameliorates DSS-Induced Colitis through
Inhibiting NLRP3 Inflammasome in Macrophages.
AB - Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the
underlying mechanism remains unclear. In the present study, we examined whether
activation of CB2R could suppress the nucleotide-binding domain and leucine-rich
repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from
C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the
components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1beta
and IL-1beta and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and
SQSTM1). Pretreatment of peritoneal macrophages with HU 308, a selective CB2R
agonist, attenuated LPS/DSS-induced NLRP3 inflammasome activation, but further
enhanced autophagy. In comparison with wild-type (WT) control, peritoneal
macrophages from CB2R knockout (KO) mice had more robust NLRP3 inflammasome
activation and attenuated autophagy upon LPS/DSS challenge. Knockdown autophagy
related gene 5 (Atg5) with a siRNA in peritoneal macrophages attenuated the
inhibitory effects of HU 308 on LPS/DSS-induced NLRP3 inflammasome activation in
vitro. In vivo, HU308 treatment attenuated DSS-induced colitis mice associated
with reduced colon inflammation and inhibited NLRP3 inflammasome activation in
wild-type mice. In CB2R KO mice, DSS-induced inflammation and NLRP3 inflammasome
activation were more pronounced than those in WT control. Finally, we
demonstrated that AMPK-mTOR-P70S6K signaling pathway was involved in this CB2R
mediated process. We conclude that activation of CB2R ameliorates DSS-induced
colitis through enhancing autophagy that may inhibit NLRP3 inflammasome
activation in macrophages.
PMID- 27611973
TI - Profile of Exosomal and Intracellular microRNA in Gamma-Herpesvirus-Infected
Lymphoma Cell Lines.
AB - Exosomes are small vesicles released from cells, into which microRNAs (miRNA) are
specifically sorted and accumulated. Two gamma-herpesviruses, Kaposi sarcoma
associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), encode miRNAs in
their genomes and express virus-encoded miRNAs in cells and exosomes. However,
there is little information about the detailed distribution of virus-encoded
miRNAs in cells and exosomes. In this study, we thus identified virus- and host
encoded miRNAs in exosomes released from KSHV- or EBV-infected lymphoma cell
lines and compared them with intracellular miRNAs using a next-generation
sequencer. Sequencing analysis demonstrated that 48% of the annotated miRNAs in
the exosomes from KSHV-infected cells originated from KSHV. Human mir-10b-5p and
mir-143-3p were much more highly concentrated in exosomes than in cells. Exosomes
contained more nonexact mature miRNAs that did not exactly match those in miRBase
than cells. Among the KSHV-encoded miRNAs, miRK12-3-5p was the most abundant
exact mature miRNA in both cells and exosomes that exactly matched those in
miRBase. Recently identified EXOmotifs, nucleotide motifs that control the
loading of miRNAs into exosomes were frequently found within the sequences of
KSHV-encoded miRNAs, and the presence of the EXOmotif CCCT or CCCG was associated
with the localization of miRNA in exosomes in KSHV-infected cells. These
observations suggest that specific virus-encoded miRNAs are sorted by EXOmotifs
and accumulate in exosomes in virus-infected cells.
PMID- 27611976
TI - Evaluating Muscle Mass by Using Markers of Kidney Function: Development of the
Sarcopenia Index.
AB - OBJECTIVES: Sarcopenia is associated with a poor prognosis in the ICU. The
purpose of this study was to describe a simple sarcopenia index using routinely
available renal biomarkers and evaluate its association with muscle mass and
patient outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary-care
medical center. PATIENTS: High-risk adult ICU patients from October 2008 to
December 2010. INTERVENTIONS: The gold standard for muscle mass was quantified
with the paraspinal muscle surface area at the L4 vertebrae in the subset of
individuals with an abdominal CT scan. Using Pearson's correlation coefficient,
serum creatinine-to-serum cystatin C ratio was found to be the best performer in
the estimation of muscle mass. The relationship between sarcopenia index and
hospital and 90-day mortality, and the length of mechanical ventilation was
evaluated. MEASUREMENTS AND MAIN RESULTS: Out of 226 enrolled patients, 123 (54%)
were female, and 198 (87%) were white. Median (interquartile range) age, body
mass index, and body surface area were 68 (57-77) years, 28 (24-34) kg/m, and 1.9
(1.7-2.2) m, respectively. The mean (+/- SD) Acute Physiology and Chronic Health
Evaluation III was 70 (+/- 22). ICU, hospital, and 90-day mortality rates were
5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and
muscle mass was 0.62 and coefficient of determination (r) was 0.27 (p < 0.0001).
After adjustment for Acute Physiology and Chronic Health Evaluation III, body
surface area, and age, sarcopenia index was independently predictive of both
hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on
mechanical ventilator, the duration of mechanical ventilation was significantly
lower on those with higher sarcopenia index (-1 d for each 10 unit of sarcopenia
index [95% CI, -1.4 to -0.2; p = 0.006]). CONCLUSIONS: The sarcopenia index is a
fair measure for muscle mass estimation among ICU patients and can modestly
predict hospital and 90-day mortality among patients who do not have acute kidney
injury at the time of measurement.
PMID- 27611978
TI - The Effect of High-Flow Nasal Cannula Oxygen Therapy on Mortality and Intubation
Rate in Acute Respiratory Failure: A Systematic Review and Meta-Analysis.
AB - OBJECTIVE: High-flow nasal cannulae are used in adults with or at risk of acute
respiratory failure. We conducted a systematic review and meta-analysis to
evaluate the evidence for their use in this setting. DATA SOURCES: Ovid Medline,
Embase, and Cochrane Database of Systematic Reviews. STUDY SELECTION: Databases
were searched for randomized controlled trials comparing administration of high
flow nasal cannulae with usual care (i.e., conventional oxygen therapy or
noninvasive ventilation) in adults with respiratory failure. The primary outcome
was hospital mortality; the rate of intubation and assessment of delirium and
comfort were secondary outcomes. DATA EXTRACTION: One hundred forty-seven
nonduplicate citations were screened, 32 underwent full screening and data
extraction, and 14 trials were eligible for inclusion in the review. Nine trials
were used in the meta-analysis, including a total of 2,507 subjects. DATA
SYNTHESIS: When high-flow nasal cannulae were compared with usual care, there was
no difference in mortality (high-flow nasal cannulae, 60/1,006 [6%] vs usual
care, 90/1,106 [8.1%]) (n = 2,112; p = 0.29; I, 25%; fixed effect model: odds
ratio, 0.83; 95% CI, 0.58-1.17) or rate of intubation (high-flow nasal cannulae,
119/1,207 [9.9%] vs usual care, 204/1,300 [15.7%]) (n = 2,507; p = 0.08; I, 53%;
random effect model: odds ratio, 0.63; 95% CI, 0.37-1.06). A qualitative analysis
of 13 studies on tolerability and comfort suggested that high-flow nasal cannulae
are associated with improved patient comfort and dyspnea scores. Trial sequential
analyses on primary and secondary outcomes suggested that required information
size was not reached. CONCLUSIONS: No difference in mortality or intubation was
detected in patients with acute respiratory failure treated with high-flow nasal
cannulae compared with usual care. High-flow nasal cannulae seem well tolerated
by patients. Further large randomized controlled trials are required to evaluate
their utility in this setting.
PMID- 27611979
TI - Probing the response of lung tumor cells to inflammatory microvascular
endothelial cells on fluidic microdevice.
AB - The development of cancer depends on a complex tissue microenvironment for
sustained growth, invasion, and metastasis. The extravasation of tumor cells is a
critical event in tumor metastasis. However, the process and mechanism that
underlie tumor cell extravasation remain unclear, which restricts the examination
of many tumor processes and presents a formidable hurdle to drug development. To
explore the initial steps by which lung tumor cells interact with the brain
microvascular wall in the course of extravasation, we present a simple,
inexpensive, and time-saving microfluidic device to mimic the inflammatory brain
microvascular microenvironment and to investigate both the biochemical and
mechanical causes of lung tumor cell rolling and adhesion on inflammatory
endothelium to analyze the synergistic effects on tumor extravasation under
fluidic shear stress conditions. Under microvascular inflammation induced by
tumor necrosis factor alpha, the lung tumor cells (A549 cells) displayed
significant adhesion activity. In addition, we found that this situation could be
reversed by administration of Rho/Rho-associated protein serine/threonine kinase
(ROCK) inhibitor (Y27632). We believe that this promising microdevice-based tumor
adhesion and extravasation research platform can be used to study tumor behavior
in an inflammatory vascular system and will make a valuable contribution for the
investigation of the mechanism of tumor cell extravasation.
PMID- 27611977
TI - Rural Patients With Severe Sepsis or Septic Shock Who Bypass Rural Hospitals Have
Increased Mortality: An Instrumental Variables Approach.
AB - OBJECTIVE: To identify factors associated with rural sepsis patients' bypassing
rural emergency departments to seek emergency care in larger hospitals, and to
measure the association between rural hospital bypass and sepsis survival.
DESIGN: Observational cohort study. SETTING: Emergency departments of a rural
Midwestern state. PATIENTS: All adults treated with severe sepsis or septic shock
between 2005 and 2014, using administrative claims data. INTERVENTIONS: Patients
bypassing local rural hospitals to seek care in larger hospitals. MEASUREMENTS
AND MAIN RESULTS: A total of 13,461 patients were included, and only 5.4% (n =
731) bypassed a rural hospital for their emergency department care. Patients who
initially chose a top-decile sepsis volume hospital were younger (64.7 vs 72.7
yr; p < 0.001) and were more likely to have commercial insurance (19.6% vs 10.6%;
p < 0.001) than those who were seen initially at a local rural hospital. They
were also more likely to have significant medical comorbidities, such as liver
failure (9.9% vs 4.2%; p < 0.001), metastatic cancer (5.9% vs 3.2%; p < 0.001),
and diabetes with complications (25.2% vs 21.6%; p = 0.024). Using an
instrumental variables approach, rural hospital bypass was associated with a 5.6%
increase (95% CI, 2.2-8.9%) in mortality. CONCLUSIONS: Most rural patients with
sepsis seek care in local emergency departments, but demographic and disease
oriented factors are associated with rural hospital bypass. Rural hospital bypass
is independently associated with increased mortality.
PMID- 27611980
TI - Cerebellar level of neurotransmitters in rats exposed to paracetamol during
development.
AB - BACKGROUND: The present study was designed to clarify the effect of prenatal and
postnatal paracetamol administration on the neurotransmitter level and balance of
amino acids in the cerebellum. METHODS: Biochemical analysis to determine the
concentration of neurotransmitters in this brain structure was performed on two
month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5,
n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and
until the completion of the second month of life, when the experiment was
terminated. Control animals were given tapped water (Con, n=10). The cerebellar
concentration of monoamines, their metabolites and amino acids were assayed using
High Performance Liquid Chromatography (HPLC). RESULTS: The present experiment
demonstrates that prenatal and postnatal paracetamol exposure results in
modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA
and MHPG levels. CONCLUSION: The effect of paracetamol on monoaminergic
neurotransmission in the cerebellum is reflected by changes in the level of
catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG)
degradation. Further work is required to define the mechanism of action and
impact of prenatal and postnatal exposure to paracetamol in the cerebellum and
other structures of the central nervous system (CNS).
PMID- 27611981
TI - Surface-Enhanced Raman Scattering to Evaluate Nanomaterial Cytotoxicity on Living
Cells.
AB - The increasing number of reports about false positive or negative results from
conventional cytotoxicity assays of nanomaterials (NMs) suggests that more
reliable NM toxicity assessment methods should be developed. Here, we report a
novel approach for nanotoxicity evaluation based on surface-enhanced Raman
spectroscopy (SERS). Three model NMs were tested on two model cell lines and the
results were validated by WST-1 cytotoxicity assay and annexin V-FITC/propidium
iodide (PI) staining as apoptosis-necrosis assay. The localization of
nanoparticles (NPs) in the cells and the cellular conditions upon NP incubation
were visualized by transmission electron microscopy (TEM) and enhanced dark-field
(EDF) microscopy. SERS revealed a broader view on the consequences of cell-NM
interactions compared to the conventional cytotoxicity assays where only one
aspect of toxicity can be measured by one assay type. The results suggest that
SERS can significantly contribute to the cytotoxicity evaluation bypassing NM or
assay component-related complications with less effort.
PMID- 27611975
TI - Impact of Source Control in Patients With Severe Sepsis and Septic Shock.
AB - OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in
septic shock. Current guidelines recommend intervention for source control within
12 hours after diagnosis. We aimed to determine the epidemiology of source
control in the management of sepsis and to analyze the impact of timing to source
control on mortality. DESIGN: Prospective observational analysis of the
Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter
educational intervention to improve antibiotherapy in sepsis. SETTING: Ninety
nine medical-surgical ICUs in Spain. PATIENTS: We enrolled 3,663 patients with
severe sepsis or septic shock during three 4-month periods between 2011 and 2013.
INTERVENTIONS: Source control and hospital mortality. MEASUREMENTS AND MAIN
RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly
for abdominal, urinary, and soft-tissue infections. Compared with patients who
did not require source control, patients who underwent source control were older,
with a greater prevalence of shock, major organ dysfunction, bacteremia,
inflammatory markers, and lactic acidemia. In addition, compliance with the
resuscitation bundle was worse in those undergoing source control. In patients
who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p =
0.010); after adjustment for confounding factors, hospital mortality was also
lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational
database analysis, source control after 12 hours was not associated with higher
mortality (27.6% vs 26.8%; p = 0.789). CONCLUSIONS: Despite greater severity and
worse compliance with resuscitation bundles, mortality was lower in septic
patients who underwent source control than in those who did not. The time to
source control could not be linked to survival in this observational database.
PMID- 27611983
TI - Synthesis of LiVOPO4 by Emulsion Drying Method for Use as an Anode Material for
Rechargeable Lithium Batteries.
AB - Highly crystalline beta-LiVOPO4 was synthesized from a water-in-oil emulsion. At
400 degrees C in ambient air, removal of the oil phase from the emulsion
precipitates resulted in a poorly crystalline intermediate compound. On
increasing the temperature to 750 degrees C under Ar, a single phase was formed.
Rietveld refinement of the X-ray diffraction (XRD) data obtained from the product
heated at 750 degrees C indicated that the product has an orthorhombic beta
LiVOPO4 olivine structure with no impurities. Although the beta-LiVOPO4 had an
irreversible capacity in the first cycle, the electrode exhibited stable
cyclability for 100 cycles, maintaining approximately 85.5% (573 mAh g-1) of the
first charge capacity (670 mAh g-1). In addition, the beta-LiVOPO4 electrode had
a high capacity even at high rates: 601 mAh g-1 at 1C rate (670 mA g-1) and 373
mAh g-1 at 30C rates (20.1 A g-1). Consolidating the results from XRD, X-ray
photoelectron spectroscopy, and time-of-flight secondary mass spectroscopy, we
suggest that the electrochemical activity of the beta-LiVOPO4 arises from the
conversion reaction accompanied by the formation of Li2O and Li3PO4. In addition,
the ion-conducting Li3PO4 contributes to high capacity delivery at high rates up
to a C-rate of 30.
PMID- 27611982
TI - Boldine Inhibits Mouse Mammary Carcinoma In Vivo and Human MCF-7 Breast Cancer
Cells In Vitro.
AB - Boldine is an aporphine alkaloid widely consumed in the folk medicine of some
regions. Its anticancer potential has been shown but not yet elucidated. We
compared the antitumor effect of orally and parenterally applied boldine in mice
bearing solid Ehrlich tumor. We also explored the effects of boldine on breast
adenocarcinoma MCF-7 cells in vitro. Repeated i. p. injections of 30, 60, or 90
mg boldine/kg, either alone or combined with doxorubicin, slowed tumor growth in
vivo. The latter two doses also prolonged the post-therapeutic survival of the
mice. When fed food supplemented with boldine at a dose of 90 mg/kg, the tumor
bearing mice survived significantly longer, but there was no effect on tumor
size. Interestingly, continuous p. o. administration did not produce detectable
levels of boldine in plasma or tissue samples, in contrast to high but short
lived concentrations after i. p. injections. There was neither antagonism nor
synergism between boldine and doxorubicin, except a possible synergism of i. p.
boldine 90 mg/kg combined with doxorubicin when compared with doxorubicin
alone.Boldine was cytotoxic to MCF-7 cells and reduced their viability and
proliferation in vitro. Exposure to boldine decreased bromodeoxyuridine
incorporation and histone H3 phosphorylation but did not induce apoptosis.
Boldine treatment resulted in p38, ERK, and JNK activation in the mitogen
activated protein kinase pathway in a dose-dependent manner. Since
bioavailability in mice seems to be different from that reported in rats,
pharmacokinetic studies in humans are needed to evaluate the role of boldine in
the beneficial effects of Boldo infusions.
PMID- 27611984
TI - Assessment of systemic cellular inflammatory response after spontaneous
intracerebral hemorrhage.
AB - OBJECTIVE: After spontaneous intracerebral hemorrhage (ICH) a local and systemic
inflammatory response is activated. Interleukin-6 (IL) is one of most relevant
orchestrators of inflammatory responses in the brain and is released from
multiple immune cells, including neutrophils. Herby we assessed the relevance of
systemic inflammation in patients suffering ICH. METHODS: From October 2010 to
October 2011 we included in our routine of laboratory investigations besides to C
reactive protein (CRP), the addition of IL-6 and an analysis of the subpopulation
of circulating blood cells. Values at admission, at 3rd and 7th day after
admission were evaluated. We analyzed 43 patients with non-traumatic ICH; stroke
related ICH or tumor associated hemorrhage were excluded. Outcome variables were
30 and 90-day mortality and NIHSS at discharge. A natural logarithmic
transformation of IL-6, lymphocytes, and monocytes was used. RESULTS: 8.6% died
within 30-days and mortality increased to 39.5% at 90th day. Total leukocytes and
neutrophils as well as IL-6 at admission were statistically significant increased
among patients who died within 30days after ICH onset (p=0.002). IL-6 and CRP in
follow-up (3rd and 7th day) were higher among patients with poor outcome (NIHSS
>15). The number of circulating lymphocytes and monocytes was not different in
measurement. Leukocytes and neutrophils at 3rd day after admission were augmented
in patients with respiratory infection and CRP in follow-up increased if some
kind of infection was clinically or microbiologically detected. IL-6 at admission
and in follow-up and monocytes at 7th day were related to ICH volume. CRP-values
at 3rd or 7th day but not at admission were associated to bigger ICH-volume. The
values of IL-6 were highly correlated to 30-day mortality and volume of ICH as
CRP only with ICH volume. CONCLUSION: After ICH onset a systemic activation of
immune system seems to be induced and may be influencing outcome. Peripheral
recruitment of leukocytes, especially neutrophils could be a target for future
therapeutic interventions. Because of the tighter correlation of IL-6 at
admission, it might be more accurate for prognostic issues than CRP.
PMID- 27611986
TI - Neuromuscular transmission abnormalities in myotonic dystrophy type 1: A
neurophysiological study.
AB - OBJECTIVES: Weakness and fatigue are frequent symptoms in myotonic dystrophy type
1 (DM1), mainly as a result of muscle impairment. However, neuromuscular junction
(NMJ) abnormalities could play an additional role in determining these
manifestations. We aimed to document the possible NMJ involvement in DM1.
PATIENTS AND METHODS: In order to substantiate this hypothesis we performed low
rate repetitive nerve stimulation (RNS) and single fiber electromyography
(SFEMG), in 14 DM1 subjects. RESULTS: RNS resulted abnormal in four patients
while SFEMG revealed a pathological jitter in ten. A significative correlation
was found between jitter values and decrementing response (p<0.000311; r=0.822).
CONCLUSION: These results suggest a possible involvement of NMJ in DM1.
PMID- 27611985
TI - Recombinant human erythropoietin improves functional recovery in patients with
severe traumatic brain injury: A randomized, double blind and controlled clinical
trial.
AB - OBJECTIVE: To investigate the short-term effect of recombinant human
erythropoietin (EPO) on patients with severe traumatic brain injury. METHODS: One
hundred and fifty-nine patients with severe traumatic brain injury were randomly
divided into EPO (n=79) and control group (n=80). EPO group was treated with
subcutaneous injection of EPO (100 units/kg) on day 1, 3, 6, 9 and 12 following
the brain injury. Glasgow outcome scores (GOS) were used to evaluate the outcomes
three months after the treatment. Serum neuron specific enolase (NSE) and S
100beta protein were measured within the first three months after treatment.
RESULTS: In the end, 146 patients (75 of the EPO group and 71 of the control
group) completed the trial. Three months after the treatment, Good recovery was
found in 33.3% of the EPO and 12.6% of the control group patients (p<0.05). Serum
NSE and S-100beta protein were decreased gradually in both groups after
treatment, but their levels in the EPO group were lower than that of control
group (p<0.05). There was no statistically significant difference in blood
pressure, hemoglobin levels, pneumonia, sepsis or thromboembolic events between
the two groups three months after the treatment (p>0.05). CONCLUSION: Treatment
with five doses of recombinant human erythropoietin is associated with an
improved functional recovery in patients with severe traumatic brain injury. This
treatment does not seem to increase the risk of thromboembolic events or severe
infections.
PMID- 27611988
TI - Fisher, Neyman, and Bayes at FDA.
AB - The wise use of statistical ideas in practice essentially requires some Bayesian
thinking, in contrast to the classical rigid frequentist dogma. This dogma too
often has seemed to influence the applications of statistics, even at agencies
like the FDA. Greg Campbell was one of the most important advocates there for
more nuanced modes of thought, especially Bayesian statistics. Because two
brilliant statisticians, Ronald Fisher and Jerzy Neyman, are often credited with
instilling the traditional frequentist approach in current practice, I argue that
both men were actually seeking very Bayesian answers, and neither would have
endorsed the rigid application of their ideas.
PMID- 27611987
TI - Dengue encephalitis presenting with nonconvulsive status epilepticus: A case
report.
PMID- 27611989
TI - Interactive effect of inoculant and dried jujube powder on the fermentation
quality and nitrogen fraction of alfalfa silage.
AB - The interactive effect of inoculants and dried jujube powder (DJP) on the
fermentation and nitrogen fraction (PA, PB1, PB2, PB3 and PC fractions) of
alfalfa silage was investigated. Three of the Lactobacillus plantarum inoculants
(LP1, LP2 or LP3) were used. The DJP was added at rates of 0, 3, 6, 9, 12 or 15%
of the whole fresh forage. The combination of DJP and inoculants decreased the pH
value and ammonia nitrogen content and increased the PC portion. As the DJP ratio
increased, there was a peak in lactic acid : acetic acid ratio (12% of DJP ratio)
and PB2 fraction (9% of DJP ratio) while the PA content decreased linearly. The
LP1 and LP2 had the highest lactic acid content. Inoculants decreased the PB1
portion of true protein. The LP1 treated silage had the highest acetic acid
content with the lowest lactic acid : acetic acid ratio and had lower PB3 and PC
and higher PB2 than LP2 or LP3 treated silages. The result showed that the
application of DJP or inoculants have positive effect on the fermentation,
nutrition and N fraction value in the high moisture alfalfa silages, and the
combination of DJP and inoculants preserves best.
PMID- 27611991
TI - Comparison of Pharmacokinetics and Tissue Distribution Kinetics of Roxithromycin
and Expression of CYP 3A1 between Pregnant Mice and Foetuses.
AB - The roxithromycin, macrolide antibiotics, is recommended for treating mycoplasma
infection and has the potential to be administered to pregnant women who are
susceptible to the infection. This study compared the pharmacokinetic properties
and tissue distribution of roxithromycin among pregnant mice and their foetuses.
We also determined the level of CYP3A1, a major enzyme for roxithromycin
metabolism, in liver microsomes and investigated the placental transport
properties of roxithromycin. Biosamples were collected from female mice at
gestational day 17 after a single intragastric administration of roxithromycin. A
sensitive and specific liquid chromatography-tandem mass spectroscopy method was
developed to detect the drug concentration and to obtain kinetic data. The level
of CYP3A1 was significantly lower in foetal liver compared with that in maternal
liver according to Western blot data, suggesting a decreased metabolism and
prolonged half-life of roxithromycin in the foetus. The tissue distributions of
roxithromycin were similar between mother and foetus, indicating that the
placental barrier did not block the transport of roxithromycin from mother to
foetus. The current findings are consistent with the clinical efficacy of
roxithromycin in both pregnant mothers and foetuses. Based on this study, it is
feasible and reasonable to predict the transport properties of other lipophilic
drugs during pregnancy.
PMID- 27611990
TI - Reduced GABA and altered somatosensory function in children with autism spectrum
disorder.
AB - BACKGROUND: Abnormal responses to tactile stimuli are a common feature of autism
spectrum disorder (ASD). Several lines of evidence suggest that GABAergic
function, which has a crucial role in tactile processing, is altered in ASD. In
this study, we determine whether in vivo GABA levels are altered in children with
ASD, and whether alterations in GABA levels are associated with abnormal tactile
function in these children. METHODS: GABA-edited magnetic resonance spectroscopy
was acquired in 37 children with Autism and 35 typically developing children
(TDC) from voxels over primary sensorimotor and occipital cortices. Children
performed tactile tasks previously shown to be altered in ASD, linked to
inhibitory mechanisms. Detection threshold was measured with- and without the
presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination
was measured with- and without the presence of an adapting stimulus, and
frequency discrimination was measured. RESULTS: Sensorimotor GABA levels were
significantly reduced in children with autism compared to healthy controls.
Occipital GABA levels were normal. Sensorimotor GABA levels correlated with
dynamic detection threshold as well as with the effect of sub-threshold
stimulation. Sensorimotor GABA levels also correlated with amplitude
discrimination after adaptation (an effect absent in autism) and frequency
discrimination in controls, but not in children with autism. CONCLUSIONS: GABA
levels correlate with behavioral measures of inhibition. Children with autism
have reduced GABA, associated with abnormalities in tactile performance. We show
here that altered in vivo GABA levels might predict abnormal tactile information
processing in ASD and that the GABA system may be a future target for therapies.
Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 27611993
TI - Prenatal lead exposure and childhood blood pressure and kidney function.
AB - BACKGROUND: Exposure to lead, a common environmental pollutant, is known to cause
cardiovascular and nephrotoxic effects in adults. Potential effects of early-life
lead exposure on these functions are, however, less well characterized.
OBJECTIVES: To assess blood pressure and kidney function in preschool-aged
children in relation to prenatal lead exposure. METHODS: This prospective study
in rural Bangladesh measured children's systolic and diastolic blood pressure in
triplicate at the follow-up at 4.5+/-0.11 years. Their kidney function was
assessed by the estimated glomerular filtration rate (eGFR), calculated based on
serum cystatin C concentrations, and by kidney volume, measured by sonography.
Exposure to lead was assessed by concentrations in the mothers' blood
(erythrocyte fraction; Ery-Pb) in gestational weeks (GW) 14 and 30, the effects
of which were evaluated separately in multivariable-adjusted linear regression
analyses. RESULTS: We found no associations between maternal exposure to lead
[n~1500 for GW14 and 700 for GW30] and children's blood pressure or eGFR.
However, we found an inverse association between late gestation lead and kidney
volume, although the sample size was limited (n=117), but not with early
gestation lead (n=573). An increase of 85ug/kg in Ery-Pb (median concentration at
GW30) was associated with a 6.0cm3/m2 decrease in kidney volume (=0.4SD;
p=0.041). After stratifying on gender, there seemed to be a somewhat stronger
association in girls. CONCLUSIONS: Prenatal lead exposure may cause long-lasting
effects on the kidney. This warrants follow-up studies in older children, as well
as additional studies in other populations.
PMID- 27611992
TI - Study on the association between ambient temperature and mortality using
spatially resolved exposure data.
AB - There are many studies that have posited an association between extreme
temperature and increased mortality. However, most studies use temperature at a
single station per city as the reference point to analyze deaths. This leads to
exposure misclassification and usually the exclusion of exurban, small town, and
rural populations. In addition, few studies control for confounding by PM2.5,
which is expected to induce upward bias. The high-resolution temperature and
PM2.5 data at a resolution of 1km2 were derived from satellite images and other
land use sources. To capture the nonlinear association of temperature with
mortality we fit a piecewise linear spline function for temperature, with a
change in slope at -1 degrees C and 28 degrees C, the temperature threshold at
which mortality in Georgia, North Carolina, and South Carolina increases due to
cold and heat, respectively. We conducted stratified analyses by age group, sex,
race, education, and urban vs nonurban, as well as sensitivity analyses of
different temperature threshold and covariate sets. We found a 0.19% (95% CI=
0.98, 1.34%) increase in mortality for each 1 degrees C decrease in temperature
below -1 degrees C and a 2.05% (95% CI=0.87, 3.24%) increase in mortality for
each 1 degrees C increase in temperature above 28 degrees C, a 79.8% larger
effect size for heat compared to the station-based metric. The effect estimates
relying on the monitoring stations were 0.09% (95% CI=-0.79, 0.95%) and 1.14%
(95% CI=0.08, 1.57%) for the equivalent temperature changes. The estimates were
not confounded by PM2.5. Children under 15 years of age had the largest
percentage increase per 1 degrees C increase in temperature (8.19%, 95% CI=-0.38
to 17.49%) followed by Blacks (4.35%, 95% CI=2.22 to 6.53%). Higher education was
a protective factor for the effect of extreme temperature on mortality. There was
a suggestion that people in less urban areas were more susceptible to extreme
temperature. The relationship between temperature and mortality was stronger when
using exposure data with more spatial variability than using exposure data based
on existing monitors alone.
PMID- 27611994
TI - Time Course Analysis of Enzyme-Catalyzed DNA Polymerization.
AB - Extracting kinetic parameters from DNA polymerase-catalyzed processive
polymerization data using traditional initial-rate analysis has proven to be
problematic for multiple reasons. The first substrate, DNA template, is a
heterogeneous polymer and binds tightly to DNA polymerase. Further, the affinity
and speed of incorporation of the second substrate, deoxynucleoside triphosphate
(dNTP), vary greatly depending on the nature of the templating base and
surrounding sequence. Here, we present a mathematical model consisting of the DNA
template-binding step and a Michaelis-Menten-type nucleotide incorporation step
acting on a DNA template with a finite length. The model was numerically
integrated and globally fitted to experimental reaction time courses. The time
courses were determined by monitoring the processive synthesis of
oligonucleotides of lengths between 50 and 120 nucleotides by DNA polymerase I
(Klenow fragment exo-) using the fluorophore PicoGreen. For processive
polymerization, we were able to estimate an enzyme-template association rate k1
of 7.4 MUM-1 s-1, a disassociation rate k-1 of 0.07 s-1, and a Kd of 10 nM, and
the steady-state parameters for correct dNTP incorporation give kcat values of
2.5-3.3 s-1 and Km values of 0.51-0.86 MUM. From the analysis of time courses
measured between 5 and 25 degrees C, an activation energy for kcat of 82 kJ mol
1 was calculated, and it was found that up to 73% of Klenow fragment becomes
inactivated or involved in unproductive binding at lower temperatures. Finally, a
solvent deuterium kinetic isotope effect (KIE) of 3.0-3.2 was observed under
processive synthesis conditions, which suggests that either the intrinsic KIE is
unusually high, at least 30-40, or previous findings, showing that the phosphoryl
transfer step occurs rapidly and is flanked by two slow conformational changes,
need to be re-evaluated. We suggest that the numerical integration of rate
equations provides a high level of flexibility and generally produces superior
results compared to those of initial-rate analysis in the study of DNA polymerase
kinetics and, by extension, other complex enzyme systems.
PMID- 27611995
TI - Protein Tyrosine Phosphatase N2 Is a Positive Regulator of Lipopolysaccharide
Signaling in Raw264.7 Cell through Derepression of Src Tyrosine Kinase.
AB - T cell protein tyrosine phosphatase N2 (PTPN2) is a phosphotyrosine-specific
nonreceptor phosphatase and is ubiquitously expressed in tissues. Although PTPN2
functions as an important regulator in different signaling pathways, it is still
unclear what is specific target protein of PTPN2 and how is regulated in
lipopolysaccharide (LPS)-induced inflammatory signaling pathway. Here, we found
that PTPN2 deficiency downregulated the expression of LPS-mediated pro
inflammtory cytokine genes. Conversely, overexpression of PTPN2 in Raw264.7 cells
enhanced the expression and secretion of those cytokines. The activation of MAPK
and NF-kappaB signaling pathways by LPS was reduced in PTPN2-knockdowned cells
and ectopic expression of PTPN2 reversed these effects. Furthermore, we found
that PTNP2 directly interacted with Src and removed the inhibitory Tyr527
phosphorylation of Src to enhance the activatory phosphorylation of Tyr416
residue. These results suggested that PTPN2 is a positive regulator of LPS
induced inflammatory response by enhancing the activity of Src through targeting
the inhibitory phosphor-tyrosine527 of Src.
PMID- 27611996
TI - p27Kip1 Is Required to Mediate a G1 Cell Cycle Arrest Downstream of ATM following
Genotoxic Stress.
AB - The DNA damage response (DDR) is a coordinated signaling network that ensures the
maintenance of genome stability under DNA damaging stress. In response to DNA
lesions, activation of the DDR leads to the establishment of cell cycle
checkpoints that delay cell-cycle progression and allow repair of the defects.
The tumor suppressor p27Kip1 is a cyclin-CDK inhibitor that plays an important
role in regulating quiescence in a variety of tissues. Several studies have
suggested that p27Kip1 also plays a role in the maintenance of genomic integrity.
Here we demonstrate that p27Kip1 is essential for the establishment of a G1
checkpoint arrest after DNA damage. We also uncovered that ATM phosphorylates
p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its
stabilization after induction of DNA double-strand breaks. Inhibition of this
stabilization by replacing endogenous p27Kip1 with a Ser-140 phospho-mutant
(S140A) significantly sensitized cells to IR treatments. Our findings reveal a
novel role for p27Kip1 in the DNA damage response pathway and suggest that part
of its tumor suppressing functions relies in its ability to mediate a G1 arrest
after the induction of DNA double strand breaks.
PMID- 27611997
TI - Anatomical and Technical Factors Influence the Rate of In-Stent Restenosis
following Carotid Artery Stenting for the Treatment of Post-Carotid
Endarterectomy Stenosis.
AB - BACKGROUND: Carotid artery stenting (CAS) has been advocated as an alternative to
redo surgery for the treatment of post-carotid endarterectomy (CEA) stenosis.
This study analyzed the efficacy of CAS for post-CEA restenosis, focusing on an
analysis of technical and anatomical predictive factors for in-stent restenosis.
METHODS: We performed a retrospective monocentric study. We included all patients
who underwent CAS for post-CEA restenosis at our institution from July 1997 to
November 2013. The primary endpoints were the technical success, the presence of
in-stent restenosis >50% or occlusion, either symptomatic or asymptomatic, during
the follow-up period, and risk factors for restenosis. The secondary endpoints
were early and late morbidity and mortality (TIA, stroke, myocardial infarction,
or death). RESULTS: A total of 153 CAS procedures were performed for post-CEA
restenosis, primarily because of asymptomatic lesions (137/153). The technical
success rate was 98%. The 30-day perioperative stroke and death rate was 2.6%
(two TIAs and two minor strokes), and rates of 2.2% (3/137) and 6.2% (1/16) were
recorded for asymptomatic and symptomatic patients, respectively. The average
follow-up time was 36 months (range, 6-171 months). In-stent restenosis or
occlusion was observed in 16 patients (10.6%). Symptomatic restenosis was
observed in only one patient. We found that young age (P = 0.002), stenosis > 85%
(P = 0.018), and a lack of stent coverage of the common carotid artery (P =
0.006) were independent predictors of in-stent restenosis. CONCLUSION: We
identified new risk factors for in-stent restenosis that were specific to this
population, and we propose a technical approach that may reduce this risk.
PMID- 27611999
TI - (Re)visualizing Black lesbian lives, (trans)masculinity, and township space in
the documentary work of Zanele Muholi.
AB - This article explores the politics of representing Black queer and trans
subjectivities in the recent documentary film and photography of South African
lesbian visual activist Zanele Muholi. While Muholi's work has been most often
been positioned as an artistic response to the hate-crimes and violence
perpetuated against Black lesbians in South African townships, most notably acts
of sexual violence known increasingly as corrective rape, I argue that Muholi's
documentary texts trouble the spatial, gendered, and highly racialized
articulations that make up an increasingly global corrective rape discourse. The
article considers how her visual texts foreground and (re)visualize Black queer
and trans gender experiences that relocate, challenge, collaborate with, and at
times, perform, masculinity as means to subvert heterosexist and racist
constructions of township space and the Black gendered body.
PMID- 27611998
TI - Effects of Early Intervention with Sodium Butyrate on Gut Microbiota and the
Expression of Inflammatory Cytokines in Neonatal Piglets.
AB - Butyrate in the gut of animals has potential properties including regulating the
innate immune, modulating the lipid metabolism, and protecting gut healthy. So
far, only limited information on the impact of butyrate on the neonatal is
available. This study aimed to investigate effects of oral administration of
sodium butyrate (SB) on gut microbiota and the expression of inflammatory
cytokine in neonatal piglets. Ten litters of crossbred newborn piglets were
randomly allocated to the SB and control (CO) groups, each group consisted of
five litters (replicates). Piglets in the SB group were orally administrated with
7 to 13 ml sodium butyrate solution (150 mmol/l) per day from the age of 1 to 7
days, respectively; piglets in the CO group were treated with the same dose of
physiological saline. On days 8 and 21 (of age), gut digesta and tissues were
collected for the analysis of microbiota, butyrate concentration and gene
expression of inflammatory cytokine. Results showed that there was no difference
in the butyrate concentration in the gut of piglets on days 8 and 21 between two
groups. Real-time PCR assay showed that SB had no effect on the numbers of total
bacteria in the stomach, ileum, and colon. MiSeq sequencing of the V3-V4 region
of the 16S rRNA gene revealed that SB increased the richness in the stomach and
colon, and the diversity of colonic microbiota on day 8 (P < 0.05). Genera
Acinetobacter, Actinobacillus, Facklamia, Globicatella, Kocuria, Rothia,
unclassified Leptotrichiaceae, unclassified Neisseriaceae, and unclassified
Prevotellaceae in the stomach were increased in relative abundance by SB
treatment, whereas the abundances of Lactobacillus decreased on day 8 (P < 0.05).
At the genus and operational taxonomic unit (OTU) levels, SB had low impact on
bacterial community in the ileum and colon on days 8 and 21. SB treatment
decreased the expression of IL-6, IL-8, IFN-gamma, IL-10, TGF-beta, and histone
deacetylase 1 (HDAC1) in the ileum of piglets on day 8 (P < 0.05). SB treatment
down-regulated the expression of IL-8, IFN-gamma, and IL-1beta on day 21 (P <
0.05). Correlation analysis on the combined datasets revealed some potential
relationships between gut microbiota and the expression of inflammatory
cytokines. The results show that early intervention with sodium butyrate can
modulate the ileum inflammatory cytokine in neonatal piglets with low impact on
intestinal microbial structure, which suggests oral administration of SB may have
a benefit role in the health of neonatal piglets.
PMID- 27612000
TI - Probabilistic modelling to assess exposure to three artificial sweeteners of
young Irish patients aged 1-3 years with PKU and CMPA.
AB - The choice of suitable normal foods is limited for individuals with particular
medical conditions, e.g., inborn errors of metabolism (phenylketonuria - PKU) or
severe cow's milk protein allergy (CMPA). Patients may have dietary restrictions
and exclusive or partial replacement of specific food groups with specially
formulated products to meet particular nutrition requirements. Artificial
sweeteners are used to improve the appearance and palatability of such food
products to avoid food refusal and ensure dietary adherence. Young children have
a higher risk of exceeding acceptable daily intakes for additives than adults due
to higher food intakes kg-1 body weight. The Budget Method and EFSA's Food
Additives Intake Model (FAIM) are not equipped to assess partial dietary
replacement with special formulations as they are built on data from dietary
surveys of consumers without special medical requirements impacting the diet. The
aim of this study was to explore dietary exposure modelling as a means of
estimating the intake of artificial sweeteners by young PKU and CMPA patients
aged 1-3 years. An adapted validated probabilistic model (FACET) was used to
assess patients' exposure to artificial sweeteners. Food consumption data were
derived from the food consumption survey data of healthy young children in
Ireland from the National Preschool and Nutrition Survey (NPNS, 2010-11).
Specially formulated foods for special medical purposes were included in the
exposure model to replace restricted foods. Inclusion was based on
recommendations for adequate protein intake and dietary adherence data. Exposure
assessment results indicated that young children with PKU and CMPA have higher
relative average intakes of artificial sweeteners than healthy young children.
The reliability and robustness of the model in the estimation of patient additive
exposures was further investigated and provides the first exposure estimates for
these special populations.
PMID- 27612001
TI - Imaging and Histopathologic Features of BI-RADS 3 Lesions Upgraded during Imaging
Surveillance.
AB - To evaluate imaging and histopathologic differences between screen-detected
benign and malignant upgraded lesions initially assessed as BI-RADS 3 at
diagnostic evaluation. An IRB approved retrospective review of the mammography
data base from January 1, 2004 to December 31, 2008 identified 1,188 (1.07%) of
110,776 screening examinations assessed as BI-RADS 3 following diagnostic
evaluation at our academic center (staffed by breast specialists) or our
outpatient center (staffed by general radiologists), 1,017 with at least 24
months follow-up or biopsy. Sixty (5.9%) BI-RADS 3 lesions were upgraded to BI
RADS 4 or 5 during imaging surveillance (study population). Prospective reports,
patient demographics, and clinical outcomes were abstracted from the longitudinal
medical record. Mean patient age was 54.1 years (range 35-85). Lesions consisted
of 7 masses, 12 focal asymmetries and 41 calcifications. Fifteen (25%) of 60
lesions upgraded from initial BI-RADS 3 assessment were malignant (1.47% of
total; 15/1,017 BI-RADS 3 studies). Malignancy rates by upgraded lesion type
showed no significant difference: Thirty-three (73.3%) of 45 benign upgraded
lesions were calcifications compared to 8 (53.3%) of 15 malignant upgraded
lesions (p = 0.202). Twelve (26.7%) of 45 benign upgraded lesions were masses or
focal asymmetries, compared to 7 (46.7%) of 15 upgraded malignant lesions (p =
0.202). Six (85.7%) of 7 malignant upgraded masses/focal asymmetries had no US
correlate at initial BI-RADS 3 assessment compared to 7 (58.3%) of 12 benign
upgraded masses/focal asymmetries (p = 0.33). Breast-imaging specialists
interpreted 21 studies, 3 (14.3%) malignant; general radiologists interpreted 39
studies, 12 (30.8%) malignant (p = 0.218). There was no significant difference in
malignancy rate among different types of upgraded mammographic lesions, nor
depending on subspecialty interpretation versus nonsubspecialist interpretation.
Although calcifications made up a majority of upgraded lesions, most were benign,
suggesting that decreased surveillance of calcifications may be appropriate.
PMID- 27612002
TI - The value of spectral imaging to reduce artefacts in the body after 125 I seed
implantation.
AB - INTRODUCTION: To explore the value of gemstone spectral imaging (GSI) and metal
artefact reduction sequence (MARs) to reduce the artefacts of metal seeds.
METHODS: Thirty-five patients with 125 I seed implantation in their abdomens
underwent GSI CT. Six types of monochromatic images and the corresponding MARs
images at 60-110 keV (interval of 10 keV) were reconstructed. The differences in
the quality of the images of three imaging methods were subjectively assessed by
three radiologists. Length of artefacts, the CT value and noise value of tissue
adjacent to 125 I seeds, contrast-to-noise ratio (CNR), and artefact index (AI)
were recorded. RESULTS: The differences in subjective scoring were statistically
significant (t = 10.87, P < 0.001). Images at 70 keV showed the best CNR (0.84 +/
0.17) of tissues adjacent to 125 I seeds, and received the highest subjective
score (2.82 +/- 0.18). Images at 80 keV had the lowest AI (70.67 +/- 19.17).
Images at 110 keV had the shortest artefact lengths. High-density metal artefacts
in the MARs spectral images were reduced. The length of metal artefacts in images
at 110 keV was shorter than that of the polychromatic images and MARs spectral
images (t = 3.35, 3.89, P < 0.05). The difference in CNR between MARs spectral
images and polychromatic images, and images at 70 keV was statistically
significant (t = 3.57, 4.16, P < 0.01). CONCLUSIONS: Gemstone spectral imaging
technique can reduce metal artefacts of 125 I seeds effectively in CT images, and
improve the quality of images, and improve the display of tissues adjacent to 125
I seeds after implantation. MARs technique cannot reduce the artefacts caused by
radioactive seeds effectively.
PMID- 27612003
TI - Minimally Invasive Plating Osteosynthesis in the Treatment of Humeral Shaft
Fractures: A Meta-Analysis.
AB - BACKGROUND: Whether minimally invasive plating osteosynthesis (MIPO) or other
operative interventions is superior in the treatment of humeral shaft fractures
remains controversial. Therefore, we conducted a meta-analysis to quantitatively
compare the clinical outcomes of MIPO and other operative interventions in the
treatment of humeral shaft fractures. METHODS: Pubmed, Embase, and Web of Science
were systematically searched to identify all available studies comparing clinical
outcomes between patients receiving MIPO and other operative interventions. The
weight mean difference (WMD) was pooled to compare the operative time, union
time, University of California, Los Angeles (UCLA) score, and Mayo elbow
performance index (MEPI).The risk ratio (RR) was pooled to compare the union
rate, and incidence of complications. Pooled estimates were calculated by using a
fixed-effects model or a randomized-effects model, according to the heterogeneity
among studies. RESULTS: Nine studies were included in this meta-analysis. Our
results suggest that both MIPO and other operative interventions can achieve
similar union time, UCLA score, MEPI, and union rate. However, MIPO is associated
with better outcomes including shorter operation time, and lower incidence of
radial nerve injury. CONCLUSION: Evidence from this meta-analysis demonstrated
that, MIPO is effective but safer than other operative interventions in the
treatment of humeral shaft fracture. However, due to the potential limitations in
this meta-analysis, randomized controlled trials with larger sample sizes using
appropriate blinding methods are needed to confirm these findings.
PMID- 27612004
TI - Student conceptions of feedback: Impact on self-regulation, self-efficacy, and
academic achievement.
AB - BACKGROUND: Lecturers give feedback on assessed work in the hope that students
will take it on board and use it to help regulate their learning for the next
assessment. However, little is known about how students' conceptions of feedback
relate to students' self-regulated learning and self-efficacy beliefs and
academic performance. AIMS: This study explores student beliefs about the role
and purpose of feedback and the relationship of those beliefs to self-reported
self-regulation and self-efficacy, and achievement. SAMPLE: A total of 278
university students in a general education course on learning theory and
approaches in a research-intensive university. METHODS: Self-reported survey
responses for students' conceptions of feedback (SCoF), self-regulation (SRL),
academic self-efficacy (ASE), and Grade Point Average (GPA) were evaluated first
with confirmatory factor analysis and then interlinked in a structural equation
model. RESULTS AND CONCLUSIONS: Three SCoF factors predicted SRL and/or GPA. The
SCoF factor 'I use feedback' had positive associations with SRL (beta = .44), GPA
(beta = .45), and ASE (beta = .15). The SCoF factors 'tutor/marker comments' and
'peers help' both had negative relations to GPA (beta = -.41 and -.16,
respectively). 'Peers help' had a positive connection to SRL (beta = .21). ASE
itself made a small contribution to overall GPA (beta = .16), while SRL had no
statistically significant relation to GPA. The model indicates the centrality of
believing that feedback exists to guide next steps in learning and thus
contributes to SRL, ASE, and increased GPA.
PMID- 27612005
TI - A tentative interpretation of the TOPCAT trial based on randomized evidence from
the brain natriuretic peptide stratum analysis.
PMID- 27612007
TI - Effect of US Food and Drug Administration-Approved Pediatric Labeling on
Dispensing of Extended-Release Oxycodone in the Outpatient Retail Setting.
PMID- 27612008
TI - Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the
Synthesis of C-Aryl Glycosides.
AB - We demonstrate that configurationally stable anomeric stannanes undergo a
stereospecific cross-coupling reaction with aromatic halides in the presence of a
palladium catalyst with exceptionally high levels of stereocontrol. In addition
to a broad substrate scope (>40 examples), this reaction eliminates critical
problems inherent to nucleophilic displacement methods and is applicable to
(hetero)aromatics, peptides, pharmaceuticals, common monosaccharides, and
saccharides containing free hydroxyl groups.
PMID- 27612009
TI - Cognitive functioning, cognitive reserve, and residential care placement in
patients with Alzheimer's and related dementias.
AB - OBJECTIVE: To test the hypothesis that patients with mild to moderate dementia
with higher initial cognitive reserve (higher education levels exhibit faster
cognitive decline at later stages of disease progression as they approach
residential care (RC) placement. METHOD: Two provincial administrative databases
were used. One contained individuals' scores of cognitive functioning (assessed
at 6- to 12-month intervals using the Standardized Mini-Mental State Examination,
SMMSE, 2007-2014) and education level; the second (BC Ministry of Health Home and
Community Care database, 2001-2014) contained individuals' RC placement; N =
10531. RESULTS: During 2.5-0.5 years prior to placement, SMMSE scores of patients
with 0-8 years of education dropped slightly (M D 20.6 to 20.0), while patients
with 9-12 years and 13+ years of education started higher (M D 21.8 and 21.4),
but decreased faster and ended up lower (M D 19.5 and 18.8). Six-months prior to
placement, SMMSE scores of all groups dropped almost 2 points. CONCLUSIONS: Once
cognitive reserve of more highly educated dementia patients is depleted and they
approach RC placement, their cognitive functioning deteriorates faster. Finding
effective interventions that maintain or enhance cognitive reserve may increase
the time in the community for dementia patients.
PMID- 27612006
TI - Peroxisome Proliferator-Activated Receptor gamma Regulates the V-Ets Avian
Erythroblastosis Virus E26 Oncogene Homolog 1/microRNA-27a Axis to Reduce
Endothelin-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung.
AB - Pulmonary hypertension (PH), a serious complication of sickle cell disease (SCD),
causes significant morbidity and mortality. Although a recent study determined
that hemin release during hemolysis triggers endothelial dysfunction in SCD, the
pathogenesis of SCD-PH remains incompletely defined. This study examines
peroxisome proliferator-activated receptor gamma (PPARgamma) regulation in SCD-PH
and endothelial dysfunction. PH and right ventricular hypertrophy were studied in
Townes humanized sickle cell (SS) and littermate control (AA) mice. In parallel
studies, SS or AA mice were gavaged with the PPARgamma agonist, rosiglitazone
(RSG), 10 mg/kg/day, or vehicle for 10 days. In vitro, human pulmonary artery
endothelial cells (HPAECs) were treated with vehicle or hemin for 72 hours, and
selected HPAECs were treated with RSG. SS mice developed PH and right ventricular
hypertrophy associated with reduced lung levels of PPARgamma and increased levels
of microRNA-27a (miR-27a), v-ets avian erythroblastosis virus E26 oncogene
homolog 1 (ETS1), endothelin-1 (ET-1), and markers of endothelial dysfunction
(platelet/endothelial cell adhesion molecule 1 and E selectin). HPAECs treated
with hemin had increased ETS1, miR-27a, ET-1, and endothelial dysfunction and
decreased PPARgamma levels. These derangements were attenuated by ETS1 knockdown,
inhibition of miR-27a, or PPARgamma overexpression. In SS mouse lung or in hemin
treated HPAECs, activation of PPARgamma with RSG attenuated reductions in
PPARgamma and increases in miR-27a, ET-1, and markers of endothelial dysfunction.
In SCD-PH pathogenesis, ETS1 stimulates increases in miR-27a levels that reduce
PPARgamma and increase ET-1 and endothelial dysfunction. PPARgamma activation
attenuated SCD-associated signaling derangements, suggesting a novel therapeutic
approach to attenuate SCD-PH pathogenesis.
PMID- 27612010
TI - Tumour and normal tissue radiobiology in mouse models: how close are mice to mini
humans?
AB - Animal modelling is essential to the study of radiobiology and the advancement of
clinical radiation oncology by providing preclinical data. Mouse models in
particular have been highly utilized in the study of both tumour and normal
tissue radiobiology because of their cost effectiveness and versatility.
Technology has significantly advanced in preclinical radiation techniques to
allow highly conformal image-guided irradiation of small animals in an effort to
mimic human treatment capabilities. However, the biological and physical
limitations of animal modelling should be recognized and considered when
interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal
tissue radioresponse has been shown to vary from human cellular and molecular
pathways. Small animal irradiation techniques utilize different anatomical
boundaries and may have different physical properties than human RT. This review
addresses the difference between the human condition and mouse models and
discusses possible strategies for future refinement of murine models of cancer
and radiation for the benefit of both basic radiobiology and clinical
translation.
PMID- 27612011
TI - Trends in blindness due to diabetic retinopathy among adults aged 18-69years over
a decade in Ireland.
AB - AIMS: To describe trends in the incidence of visual impairment and blindness due
to diabetic retinopathy among adults aged 18-69years in Ireland between 2004 and
2013. METHODS: Data on visual impairment due to diabetic retinopathy in adults
aged 18-69years or over who are registered with the National Council for the
Blind of Ireland, (2004-2013) were analysed. Annual incidence rates were
calculated for the adult population and the population with diagnosed diabetes.
Poisson regression was used to test for changes in rates over time. The relative,
attributable and population risk of blindness and visual impairment due to
diabetic retinopathy were calculated for 2013. RESULTS: Over the decade, the
prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with
diagnosed diabetes, the incidence of visual impairment due to diabetic
retinopathy increased from 6.4 (95% CI 2.4-13.9) per 100,000 in 2004 to 11.7 (95%
CI 5.9-21.0) per 100,000 in 2013. The incidence of blindness due to diabetic
retinopathy varied from 31.9 per 100,000 (95% CI 21.6-45.7) in 2004 to 14.9 per
100,000 (95% CI 8.2-25.1) in 2013. CONCLUSIONS: Our findings indicate the need
for increased attention to preventive measures for microvascular complications
among adults with diabetes in Ireland. Retinopathy screening has been
standardised in Ireland, these findings provide useful baseline statistics to
monitor the impact of this population-based screening programme.
PMID- 27612012
TI - T-cell-restricted intracellular antigen 1 facilitates mitochondrial fragmentation
by enhancing the expression of mitochondrial fission factor.
AB - Mitochondrial morphology is dynamically regulated by the formation of small
fragmented units or interconnected mitochondrial networks, and this dynamic
morphological change is a pivotal process in normal mitochondrial function. In
the present study, we identified a novel regulator responsible for the regulation
of mitochondrial dynamics. An assay using CHANG liver cells stably expressing
mitochondrial-targeted yellow fluorescent protein (mtYFP) and a group of siRNAs
revealed that T-cell intracellular antigen protein-1 (TIA-1) affects
mitochondrial morphology by enhancing mitochondrial fission. The function of TIA
1 in mitochondrial dynamics was investigated through various biological
approaches and expression analysis in human specimen. Downregulation of TIA-1
enhanced mitochondrial elongation, whereas ectopic expression of TIA-1 resulted
in mitochondria fragmentation. In addition, TIA-1 increased mitochondrial
activity, including the rate of ATP synthesis and oxygen consumption. Further, we
identified mitochondrial fission factor (MFF) as a direct target of TIA-1, and
showed that TIA-1 promotes mitochondrial fragmentation by enhancing MFF
translation. TIA-1 null cells had a decreased level of MFF and less mitochondrial
Drp1, a critical factor for mitochondrial fragmentation, thereby enhancing
mitochondrial elongation. Taken together, our results indicate that TIA-1 is a
novel factor that facilitates mitochondrial dynamics by enhancing MFF expression
and contributes to mitochondrial dysfunction.
PMID- 27612013
TI - Silencing the epigenetic silencer KDM4A for TRAIL and DR5 simultaneous induction
and antitumor therapy.
AB - Recombinant TRAIL and agonistic antibodies to death receptors (DRs) have been in
clinical trial but displayed limited anti-cancer efficacy. Lack of functional DR
expression in tumors is a major limiting factor. We report here that chromatin
regulator KDM4A/JMJD2A, not KDM4B, has a pivotal role in silencing tumor cell
expression of both TRAIL and its receptor DR5. In TRAIL-sensitive and -resistant
cancer cells of lung, breast and prostate, KDM4A small-molecule inhibitor
compound-4 (C-4) or gene silencing strongly induces TRAIL and DR5 expression, and
causes TRAIL-dependent apoptotic cell death. KDM4A inhibition also strongly
sensitizes cells to TRAIL. C-4 alone potently inhibits tumor growth with marked
induction of TRAIL and DR5 expression in the treated tumors and effectively
sensitizes them to the newly developed TRAIL-inducer ONC201. Mechanistically, C-4
does not appear to act through the Akt-ERK-FOXO3a pathway. Instead, it switches
histone modifying enzyme complexes at promoters of TRAIL and DR5 transcriptional
activator CHOP gene by dissociating KDM4A and nuclear receptor corepressor (NCoR)
HDAC complex and inducing the recruitment of histone acetylase CBP. Thus, our
results reveal KDM4A as a key epigenetic silencer of TRAIL and DR5 in tumors and
establish inhibitors of KDM4A as a novel strategy for effectively sensitizing
tumors to TRAIL pathway-based therapeutics.
PMID- 27612014
TI - Tudor staphylococcal nuclease: biochemistry and functions.
AB - Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) is an
evolutionarily conserved protein with invariant domain composition, represented
by tandem repeat of staphylococcal nuclease domains and a tudor domain.
Conservation along significant evolutionary distance, from protozoa to plants and
animals, suggests important physiological functions for TSN. It is known that TSN
is critically involved in virtually all pathways of gene expression, ranging from
transcription to RNA silencing. Owing to its high protein-protein binding
affinity coexistent with enzymatic activity, TSN can exert its biochemical
function by acting as both a scaffolding molecule of large multiprotein complexes
and/or as a nuclease. TSN is indispensible for normal development and stress
resistance, whereas its increased expression is closely associated with various
types of cancer. Thus, TSN is an attractive target for anti-cancer therapy and a
potent tumor marker. Considering ever increasing interest to further understand a
multitude of TSN-mediated processes and a mechanistic role of TSN in these
processes, here we took an attempt to summarize and update the available
information about this intriguing multifunctional protein.
PMID- 27612015
TI - Full-length nucleotide sequence of ERMAP alleles encoding Scianna (SC) antigens.
AB - BACKGROUND: Scianna (SC) blood group system comprises two antithetical antigens,
Sc1 and Sc2, and five additional antigens. The antigens reside on a glycoprotein
encoded by the erythroblast membrane-associated protein (ERMAP) gene. For the
common ERMAP alleles, we determined the full-length nucleotide sequence that
encodes the Scianna glycoprotein. STUDY DESIGN AND METHODS: Blood donor samples
from five populations were analyzed including 20 African Americans, 10
Caucasians, 10 Thai, five Asians, and five Hispanics for a total of 100
chromosomes. An assay was devised to determine the genomic sequence of the ERMAP
gene in one amplicon, spanning 21.4 kb and covering Exons 2 to 12 and the
intervening sequence (IVS). All alleles (confirmed haplotypes) were resolved
without ambiguity. RESULTS: Among 50 blood donors, we found 80 single-nucleotide
polymorphisms (SNPs), including six novel SNPs, in 21,308 nucleotides covering
the coding sequence of the ERMAP gene and including the introns. The noncoding
sequences harbored 75 SNPs (68 in the introns and seven in the 3'-UTR). No SNP
indicative of a nonfunctional allele was detected. The nucleotide sequences for
48 ERMAP alleles (confirmed haplotypes) were determined by allele-specific
polymerase chain reaction and sequencing in 100 chromosomes. CONCLUSIONS: We
documented 48 ERMAP alleles of 21,308 nucleotides each. The two nucleotide
sequences available in GenBank for ERMAP alleles of similar length have not been
found in our 100 chromosomes. Alleles determined without ambiguity can be used as
templates to analyze next generation sequencing data, which will enhance the
reliability in clinical diagnostics.
PMID- 27612016
TI - Retinal Oxygen Saturation in Patients with Primary Open-angle Glaucoma Using a
Non-flash Hypespectral Camera.
AB - : Purpose/Aim: To investigate retinal vessel blood oxygen saturation in patients
with primary open-angle glaucoma (POAG) and healthy controls. MATERIALS AND
METHODS: A novel non-flash hyperspectral retinal camera was used to image 17
healthy individuals (mean age 69.3 +/- 6.1 years) and 22 patients with stable
POAG (mean age 69.2 +/- 5.8 years) at 548, 569, 586, 600, 605, and 610 nm
wavelengths. POAG patients were grouped as mild-moderate (n = 13) and moderate
severe (n = 9) based on Humphrey 24-2 visual field results (mean deviation [MD] <
-6 and MD >= -6; respectively). Optical density values were extracted using Image
J software for blood oxygen saturation (SO2) determination. Arteriolar and
venular SO2 were measured within 1.5 optic nerve head diameters from the disc
margin along the vessels in the inferior temporal quadrant of the tested eye per
subject. Analysis of variance (ANOVA), student t-test, and Pearson's correlation
were used for statistical analysis of the data (p < 0.05). RESULTS: Venular,
arteriolar, and arteriovenous (AV) differences in SO2 measurements were not
significantly different between controls and the combined POAG groups (p > 0.06
for all). However, mean venular SO2 was significantly higher in the POAG with MD
>= -6 dB when compared to controls and patients with mild glaucoma (p = 0.005).
The AV differences were significantly lower in patients with more severe field
defect (p = 0.006) compared to the remaining groups. No differences were found in
the mean arteriolar SO2 between the groups (p = 0.155). Significant correlations
were found only between higher visual field MD values and higher venular SO2 (p =
0.048) but not the remaining SO2 measurements. CONCLUSION: Patients with POAG and
moderate-severe visual field defect had higher venular SO2 compared to those with
mild-moderate defect and controls. This would indicate reduced oxygen consumption
in more advanced glaucoma likely as a result of ganglion cell degeneration.
PMID- 27612019
TI - Challenges and Opportunities in Rare Disease Drug Development.
AB - Each month, Clinical Pharmacology & Therapeutics focuses on a particular theme.
Twice a year, the associate editors, editors, and staff get together to discuss
journal business and spend time setting up the calendar of themes. Often, there
are no experts among us to take on a particular topic that we have chosen. The
consequence is that one or two of us take on the theme and then have a crash
course to learn as much as they can about it in order to solicit meaningful
articles. This month's theme on rare diseases is such a case.
PMID- 27612017
TI - Survival of Elderly Adults Undergoing Incident Home Hemodialysis and Kidney
Transplantation.
AB - OBJECTIVES: To compare the mortality of elderly adults with end-stage renal
disease (ESRD) treated with home hemodialysis (HD) with that of those receiving a
kidney transplant (KTx). DESIGN: Prospective cohort. SETTING: Pertinent data for
the two groups were obtained from electronic medical records from a large
dialysis provider and the U.S. Renal Data System. PARTICIPANTS: Using data from
elderly adults (aged >=65) who started home HD and underwent KTx in the US
between 2007 and 2011, a 1:1 propensity score (PS)-matched cohort of 960 elderly
adults was created, and the association between treatment modality and all-cause
mortality was examined using Cox proportional hazards and competing risk
regression survival models using modality failure as a competing event.
MEASUREMENTS: Modality of renal replacement therapy. RESULTS: The baseline mean
age +/- standard deviation of the PS-matched individuals undergoing home HD was
71 +/- 6, and that of KTx recipients was 71 +/- 5, 69% of both groups were male,
81% of those undergoing home HD and 79% of KTx recipients were white, and 11% and
12%, respectively, were African American. Median follow-up time was 205 days
(interquartile range (IQR) 78-364 days) for those undergoing home HD and 795 days
(IQR 366-1,221 days) for KTx recipients. There were 97 deaths (20%, 253/1,000
patient-years, 95% confidence interval (CI) = 207-309/1,000 patient-years) in the
home HD group and 48 deaths (10%, 45/1,000 patient-years, 95% CI = 34-60/1,000
patient-years) in the KTx group. Elderly adults undergoing home HD had a risk of
mortality that was almost five times as high as that of KTx recipients (hazard
ratio = 4.74, 95% CI = 3.25-6.91). Similar results were seen in competing risk
regression analyses (subhazard ratio = 4.71, 95% CI = 3.27-6.79). Results were
consistent across different types of kidney donors and subgroups divided
according to various recipient characteristics. CONCLUSION: Elderly adults with
ESRD who receive a KTx have greater survival than those who undergo home HD.
Further studies are needed to assess whether KTx receipt is associated with other
benefits such as better quality of life and lower hospitalization rates.
PMID- 27612022
TI - Genetic Analysis of the ZNF512B, SLC41A1, and ALDH2 Polymorphisms in Parkinson's
Disease in the Iranian Population.
AB - AIMS: Parkinson's disease (PD) is one of the most common neurodegenerative
disorders; its etiology includes both genetic and environmental factors and their
interactions. The ZNF512B, SLC41A1, and ALDH2 genes have recently been identified
as contributing to PD. In this study we investigated the association of alleles
of these genes with PD in the Iranian population. METHODS: In a case-control
study, rs2275294, rs11240569, and rs4767944, three single nucleotide
polymorphisms in ZNF512B, SLC41A1, and ALDH2 genes, respectively, were genotyped
in 490 PD patients and 490 controls. The genotype and allele frequencies were
compared between the two groups using chi-square and logistic regression tests.
RESULTS: A significant association between the rs11240569 polymorphism and a
reduced risk of PD was found (p = 0.014, OR = 0.76, 95% CI: 0.60-0.94 for allele
frequencies). We did not find any associations between PD and the rs2275294 and
rs4767944 polymorphisms. CONCLUSION: The association of rs11240569 polymorphism
in SLC41A1 gene with reduced risk of PD was replicated in our population.
PMID- 27612023
TI - Effect of smile index and incisal edge position on perception of attractiveness
in different age groups.
AB - Changes in occlusal vertical dimension (OVD) and age have been found to affect
Smile Index (SI, width/height of smile). Limited information is available
regarding the aesthetic effects of these changes. The objective of this study was
to evaluate the attractiveness of digitally manipulated smile images with
differences in SI and incisal edge position (IEP) judged by respondents in
different age groups. A total of 12 smile images were generated with varying SI
(3.5, 5.3, 7.2, 9.0) and IEP (High, Medium, Low). Fifty respondents each in four
age groups (15-24, 25-39, 40-54, 55+) evaluated the attractiveness of the 12
images using a 0-10 visual analog scale (VAS, 10 being most attractive). A
repeated-measures three-factorial mixed model assessed differences. SI, IEP and
age of respondents were found to significantly influence attractiveness score (P
< 0.01 for all). With all age groups combined, SI = 7.2/IEP = Medium was most
attractive (VAS = 7.22), followed by SI = 9.0/IEP = Medium, and SI = 5.3/IEP =
Medium (VAS = 6.53 and 6.48, respectively). SI = 3.5/IEP = High and SI = 3.5/IEP
= Low were least attractive (VAS = 1.99 and VAS = 2.58, respectively). Age group
significantly influenced aesthetic perception, with younger respondents more
critical in differences in SI and IEP. SI and IEP significantly influenced
attractiveness of the smile in all respondent age groups. Low SI (i.e. 3.5)
combined with high or low IEP was unattractive. Medium SI to high SI (i.e. 5.3
9.0) combined with medium IEP were considered attractive.
PMID- 27612025
TI - Tetanus in New Zealand children: Intensive care management of a vaccine
preventable disease.
AB - AIM: To review management of children admitted with tetanus to Starship
Children's Hospital from 2000 to 2013. METHODS: Retrospective chart review of
children aged 0-15 years admitted to Starship Children's Hospital with tetanus
from 2000 to 2013. Follow-up of immunisation status was via the National
Immunisation Register and/or phone contact with patient's primary health care
provider. RESULTS: Four cases of tetanus occurred, all in unimmunised children.
All four required paediatric intensive care unit admission (length of stay (LOS)
2.5-7 weeks) for ventilatory support; three required tracheostomy. Specific
tetanus treatment included metronidazole, tetanus immunoglobulin and
antispasmodic medications such as magnesium sulphate and benzodiazepines. Three
remain partially or unimmunised following discharge. CONCLUSION: Tetanus in
children is a rare but preventable life-threatening disease, requiring costly
intensive care management. Immunisation is cheap and effective in preventing
tetanus and should be offered to all children, including tetanus cases for their
future protection.
PMID- 27612024
TI - Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic
and dyslipidaemic mice by upregulating fatty acid beta-oxidation.
AB - Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis,
steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat
accumulation in the liver in the absence of excessive alcohol intake. In patients
with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic
kidney disease and the mortality rate. Although several studies have examined the
effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are
available to verify the effectiveness of PTX in treating T2D associated with
NAFLD. In this study, we developed a combined high-fat diet-induced obesity and
low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent
NAFLD and T2D pathological condition. By combining physiological assessments,
pathological examinations, metabolomics studies on blood, urine, and liver, and
measurements of gene and protein expression, we elucidated the effectiveness and
the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic
mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and
dyslipidaemic mice by upregulating fatty acid beta-oxidation. Furthermore, the
glycolysis pathway and branched-chain amino acid-related pathways in these mice
were restored by PTX.
PMID- 27612027
TI - Studies on Mean Platelet Volume (MPV) - New Editorial Policy.
PMID- 27612026
TI - Clinical and Mutational Features of Three Chinese Children with Congenital
Generalized Lipodystrophy.
AB - OBJECTIVE: To investigate the clinical and molecular features of congenital
generalized lipodystrophy (CGL) in three Chinese patients with various typical
manifestations. METHODS: Data on clinical symptoms, results of laboratory
analyses, and previous treatments in three Chinese patients were collected by a
retrospective review of medical records. All coding regions and adjacent exon
intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase
chain reaction and sequenced. RESULTS: Generalized lipodystrophy, acanthosis
nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly
were features in all three patients. Patient 1 developed diabetes mellitus at the
early age of 2 months and he was the youngest CGL patient reported with overt
diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months.
All of the patients were found to have mutations in the BSCL2 gene, but none of
these was a novel mutation. We did not find any AGPAT2 mutation in our patients.
CONCLUSION: All of our patients exhibited characteristic features of CGL due to
mutations in the BSCL2 gene.
PMID- 27612028
TI - Trim27 interacts with Slx2, is associated with meiotic processes during
spermatogenesis.
AB - ABSTARCT Formation of the XY body is believed to prevent recombination between X
and Y chromosomes during meiosis. We recently demonstrated that SYCP3-like X
linked 2 (Slx2) could be involved in synaptonemal complex formation as well as XY
body maintenance during meiosis. In order to further investigate the role and
composition of XY body protein complexes in meiotic processes and
spermatogenesis, a yeast 2-hybrid screening was performed, and the tripartite
motif protein 27(Trim27) was found to interact with Slx2 and co-localized in the
XY body. Trim27 has a tripartite motif (TRIM) consisting of a RING finger, B-box
and coiled-coil domains, and is a transcriptional regulator that is expressed in
various tumor cell lines. In this study, we showed that Slx2 and Trim27 were
highly expressed in meiosis of mouse testis. And the Slx2/Trim27 interaction was
confirmed in vivo by co-immunoprecipitation and mammalian 2-hybrid interaction
assays. Moreover, cytoimmuno localization experiments revealed that Slx2/Trim27
was co-localized to the XY body of spermatocytes during meiosis, and
immunohistochemical results revealed co-localization of Trim27 and gamma-H2AX in
the XY body of primary spermatocytes in the mouse testis. Trim27 may therefore be
a transcriptional regulation protein connecting Slx2 and gamma-H2AX, thereby
promoting the formation of a more potent XY body protein complex in meiotic
processes and spermatogenesis. In conclusion, Trim27 connecting Slx2 may regulate
meiotic processes in multiple ways by influencing XY body formation and germ cell
proliferation during spermatogenesis.
PMID- 27612030
TI - Prognostic value of metabolic response measured by 18F-FDG-PET in oesophageal
cancer patients treated with definitive chemoradiotherapy.
AB - BACKGROUND: This study aimed to assess the efficacy of fluorine-18
fluorodeoxyglucose (F-FDG)-PET for predicting overall survival (OS) and disease
free survival (DFS) in oesophageal cancer patients after definitive
chemoradiotherapy (CRT) and prognostic importance of metabolic response detected
by post-treatment PET at least 3 months after completing CRT. MATERIALS AND
METHODS: Data from 58 oesophageal cancer patients receiving definitive CRT were
retrospectively analysed. Post-treatment F-FDG-PET was delivered at a median of
3.2 (range, 3.0-6.4) months after CRT. The impact of metabolic response
determined by post-treatment F-FDG-PET, maximum post-treatment standardized
uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on
survival was analysed. RESULTS: The median follow-up was 19.7 (range, 4.2-91.9)
months for all patients and 28.2 (range, 13.7-91.9) months for survivors. The
mean pretreatment and post-treatment SUVmax and the median percent SUV decrease
were 18.6+/-6.4, 6.2+/-4.6 and -73% (+13 to -100%). Pretreatment SUVmax was
higher in patients with locoregional or distant failure than in those without
(P<0.001). Pretreatment SUVmax was lower in patients with a complete response
(CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in
patients with CR compared with those without CR (P<0.001). CR rates detected by
post-treatment F-FDG-PET were lower in patients with lymph node metastases or
longer tumours than in those with shorter tumours or no metastases. During
multivariate analysis, post-treatment SUVmax was a significant predictor for OS,
and post-treatment SUVmax, percent SUV decrease and tumour length were
significant prognostic factors for DFS. CONCLUSION: Metabolic response assessed
by post-treatment F-FDG-PET at least 3 months after CRT showed that post
treatment SUVmax and percent SUV change were important survival predictors.
PMID- 27612029
TI - ATM/CHK/p53 Pathway Dependent Chemopreventive and Therapeutic Activity on Lung
Cancer by Pterostilbene.
AB - Among the many stilbenoids found in a variety of berries, resveratrol and
pterostilbene are of particular interest given their potential for use in cancer
therapeutics and prevention. We purified four stilbenoids from R. undulatum and
found that pterostilbene inhibits cancer cell proliferation more efficiently than
rhapontigenin, piceatannol and resveratrol. To investigate the underlying
mechanism of this superior action of pterostilbene on cancer cells, we utilized a
reverse-phase protein array followed by bioinformatic analysis and found that the
ATM/CHK pathway is modified by pterostilbene in a lung cancer cell line. Given
that ATM/CHK signaling requires p53 for its biological effects, we hypothesized
that p53 is required for the anticancer effect of pterostilbene. To test this
hypothesis, we used two molecularly defined precancerous human bronchial
epithelial cell lines, HBECR and HBECR/p53i, with normal p53 and suppressed p53
expression, respectively, to represent premalignant states of squamous lung
carcinogenesis. Pterostilbene inhibited the cell cycle more efficiently in HBECR
cells compared to HBECR/p53i cells, suggesting that the presence of p53 is
required for the action of pterostilbene. Pterostilbene also activated ATM and
CHK1/2, which are upstream of p53, in both cell lines, though pterostilbene
induced senescence was dependent on the presence of p53. Finally, pterostilbene
more effectively inhibited p53-dependent cell proliferation compared to the other
three stilbenoids. These results strongly support the potential chemopreventive
effect of pterostilbene on p53-positive cells during early carcinogenesis.
PMID- 27612031
TI - Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET
molecular imaging probe.
AB - OBJECTIVE: The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had
been found to show high uptake in tumor tissue in our previous report; however,
the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this
present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor
imaging. METHODS: The biodistribution of [C]-L-CMTP was determined in healthy
mice and the incorporation of [C]-L-CMTP into proteins was investigated. In-vitro
competitive inhibition experiments were conducted with Hepa1-6 hepatoma cell
lines. [C]-L-CMTP PET imaging was performed on S180 tumor-bearing mice and lung
tumor-bearing mice. RESULTS: Biodistribution studies showed high uptake of [C]-L
CMTP in the liver, kidney, and pancreas, but low uptake in brain. The transport
assay studies in Hepa1-6 cells suggested that [C]-L-CMTP was mainly transported
by the amino acid transport system B and LAT1. [C]-L-CMTP was not incorporated
into proteins in vitro. PET imaging showed that [C]-L-CMTP had high uptake in
S180 fibrosarcoma tumor and lung tumor. CONCLUSION: [C]-L-CMTP was not
incorporated into proteins and was mainly transported by the amino acid transport
system B and LAT1, PET imaging showed that [C]-L-CMTP had high uptake in tumor
models; it seemed to be a promising PET probe for tumor by LAT1 transport. Video
abstract: http://links.lww.com/NMC/A70.
PMID- 27612032
TI - Comparison of renal uptake of 68Ga-DOTANOC PET/CT and estimated glomerular
filtration rate before and after peptide receptor radionuclide therapy in
patients with metastatic neuroendocrine tumours.
AB - BACKGROUND: Ga-DOTA-conjugated peptide PET/CT is used widely for diagnosis and
treatment planning in patients with neuroendocrine tumours. As nephrotoxicity is
a major limiting factor during peptide receptor radionuclide therapy (PRRT), it
is important to evaluate renal function before, during and after treatment. The
aim of our study is to compare renal uptake of Ga-DOTANOC and estimated
glomerular filtration rate (eGFR) before and after PRRT and to identify any
surrogate indicators of renal toxicity. MATERIALS AND METHODS: We included 64 Ga
DOTANOC PET/CT examinations in 32 patients with metastatic neuroendocrine tumours
who underwent Y-DOTATATE therapy between May 2013 and April 2016. An amino acid
infusion was used routinely for renal protection. Renal uptake was quantified as
mean standardized uptake value (SUVmean) of both kidneys after background
subtraction. eGFR was calculated using standard software. The values were
compared and evaluation of correlation and agreement between the two parameters
was performed. RESULTS: Our study showed fair agreement between SUVmean of the
kidneys on Ga-DOTANOC PET/CT and eGFR (r=0.33) before PRRT and poor agreement
between SUVmean of the kidneys and eGFR (r=0.16) after PRRT. As expected, there
was a statistically significant difference in eGFR before and after PRRT (mean
difference=4.41+/-9.24 ml/min/1.73 m, P=0.01). On comparison of renal uptake
before and after PRRT, the post-PRRT scans showed a statistically significant
increase in uptake (SUVmean=-1.25+/-3.17, P=0.03). CONCLUSION: Renal quantitative
analysis on Ga-DOTANOC PET/CT before and after PRRT showed no significant
correlation with the eGFR. However, there was a statistically significant
increase in the renal uptake of Ga-DOTANOC, with a higher uptake after PRRT. As a
result of this pilot study, we suggest that the higher renal uptake in the post
PRRT scans could be an indicator of early renal dysfunction and could have
implications for further cycles of PRRT. Further longitudinal studies and further
evaluation of such data across multiple centres are suggested.
PMID- 27612033
TI - Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with
inconclusive conventional imaging: a multicenter study from the Netherlands.
AB - BACKGROUND: Several reports have shown good performance of fluorine-18
fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization,
although overall evidence remains scarce. We collected data from three
institutions in the Netherlands and investigated the performance of F-FCH PET-CT
as a second-line imaging modality. MATERIALS AND METHODS: We performed a
retrospective review of all patients at least 18 years who underwent F-FCH PET-CT
for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound
and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after
the administration of 2 MBq/kg F-FCH, together with a low-dose CT. RESULTS: PET
CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of
58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1,
one patient had tertiary HPT because of Alport syndrome and the remaining
patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%)
cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could
successfully localize 33/35 (94.3%), with only one false-positive result
[positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with
negative PET-CT with the 34 patients with positive PET-CT showed no significant
differences in age, sex, ratio of preoperative calcium, use of cinacalcet,
history of neck surgery, and concomitant multinodular goiter. CONCLUSION: Our
study shows excellent performance of F-FCH PET-CT in patients with HPT and
inconclusive conventional imaging. Because of its favorable characteristics with
high performance, prospective studies should be initiated to determine whether
this new technique may replace conventional sestamibi scintigraphy as a first
line imaging modality.
PMID- 27612035
TI - Should we stop offering indium-111 octreotide scans in favour of gallium-68 PET
CT scans in the UK?
PMID- 27612034
TI - The incidence of thyroid cancer in focal hypermetabolic thyroid lesions: an 18F
FDG PET/CT study in more than 6000 patients.
AB - BACKGROUND: The clinical significance of incidental thyroid abnormalities
discovered in fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT)
(FDG PET/CT) studies remains controversial. The aim of this large retrospective
study was to (a) determine the prevalence of focal F-FDG thyroid uptake on whole
body F-FDG PET/CT studies carried out for nonthyroid cancers and (b) to test
whether intense focal F-FDG thyroid uptake is associated with malignancy.
MATERIALS AND METHODS: A total of 11 921 F-FDG PET/CT studies in 6216 patients
carried out at our institution between January 2012 and December 2014 were
analyzed. We retrospectively reviewed the medical records of these patients.
Eight hundred and forty-five/6216 (13.6%) patients had a thyroid incidentaloma on
the basis of the clinical F-FDG PET/CT report. One hundred and sixty/845 (18.9%)
of these underwent ultrasound and 98 (61.3%) of these underwent a fine-needle
aspiration (FNA). Twenty-six of these 98 (26.5%) patients underwent
thyroidectomy. Thyroid lesion and background standardized uptake value (SUVs) for
each patient were measured upon review of the F-FDG PET/CT study. We measured
maximum standardized uptake value (SUVmax), thyroid to background TL/TBG, thyroid
to bloodpool TL/BP and thyroid to liver TL/L ratios in benign and malignant
lesions. Receiver operating curves were calculated to determine optimal cut-off
values between malignant and benign lesions. RESULTS: Twenty-one of the 98
patients who underwent FNA biopsy or thyroidectomy had malignant disease (21.4%).
Malignant lesions had significantly higher thyroid lesion SUVmax, TL/TBG, TL/BP,
and TL/L than benign nodules. The receiver operating curves derived cut-off ratio
TL/TBG of more than 2.0 differentiated benign from malignant lesions best with a
specificity and sensitivity of 0.76 and 0.88, respectively. CONCLUSION: The
incidence of malignancy in biopsied focal hypermetabolic thyroid lesions is
21.4%. Lesions on F-FDG PET/CT studies, with a ratio TL/TBG more than 2.0,
warrant further work-up with ultrasound and FNA to exclude malignancy.
PMID- 27612036
TI - Self-Euthanasia, the Dutch Experience: In Search for the Meaning of a Good Death
or Eu Thanatos.
AB - My main purpose in this article is to establish the meaning of a 'good death'
when death is self-chosen. I will take as my point of departure the new notion of
'self-euthanasia' and the corresponding practice that has evolved in the
Netherlands in recent years. Both physician-euthanasia and self-euthanasia refer
to an ideal process of a good death, the first being ultimately the physician's
responsibility, while the second is definitely the responsibility of the
individual choosing to die. However, if we also accept the existence of a
fundamental moral difference between ending another person's life and ending your
own life, and if we accept this moral difference to be also relevant to the
normatively laden good death, then this difference represents a strong reason for
preferring self-euthanasia to physician-euthanasia.
PMID- 27612039
TI - Sacral neuromodulation for refractory overactive bladder after prior intravesical
onabotulinumtoxinA treatment.
AB - AIMS: Sacral neuromodulation (SNM) is a well-established treatment modality for
refractory overactive bladder (OAB). There is a paucity of evidence examining the
use of SNM in patients who have received prior intravesical onabotulinumtoxinA
(BTXA) treatment. We aim to review those patients who underwent SNM for
refractory OAB following treatment with BTXA. METHODS: A retrospective review was
conducted to identify patients who had undergone prior intradetrusor BTXA for
refractory OAB, then subsequent first-stage SNM. Patient demographics,
number/dosage of BTXA, voiding diaries, and patient global impression of
improvement (PGI-I) scores were recorded. Successful first-stage SNM was defined
as subjective patient improvement of greater than 50%. Patient satisfaction and
device use at last follow-up was noted. RESULTS: Eighty-three patients were
identified having undergone SNM for OAB, of which 36 had prior BTXA treatment and
were included in the series. 23/36 (63.9%) of patients had successful first-stage
SNM, and underwent insertion of implantable pulse generator, compared to 33/47
(70.2%) in those who had never been treated with BTXA (P = 0.5). Mean PGI-I score
was 2.6 (range 1-4). With a mean follow up of 29.1 months (range 12-53), 17/23
(73.9%) were satisfied, and using the device at last follow-up. CONCLUSION: SNM
is a suitable treatment option in those patients who have had prior BTXA
treatment for refractory OAB, even in those for whom BTXA proved ineffective.
Success rates were within the published range, and comparable to our own results,
for SNM in OAB patients without prior BTXA treatment.
PMID- 27612037
TI - Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post
Partum: A Longitudinal Study.
AB - Circulating Anti-Mullerian hormone (AMH) is derived from the gonads, and is a
mixture of the prohormone (proAMH), which does not bind to AMH receptors, and
receptor-competent AMH. The functions of a hormone are partially defined by the
factors that control its levels. Ovarian reserve accounts for 55~75% of the woman
to-woman variation in AMH level, leaving over 25% of the biological variation to
be explained. Pregnancy has been reported to decrease circulating AMH levels, but
the observations are inconsistent, with the effect of pregnancy on the
bioactivity of AMH being unknown. We have therefore undertaken a longitudinal
study of circulating proAMH and total AMH during pregnancy. Serum samples were
drawn at 6-8 gestational time-points (first trimester to post-partum) from 25
healthy women with prior uneventful pregnancies. The total AMH and proAMH levels
were measured at each time-point using ELISA. The level of circulating total AMH
progressively decreased during pregnancy, in all women (p<0.001). On average, the
percentage decline between the first trimester and 36-39 weeks' gestation was
61.5%, with a standard deviation of 13.0% (range 30.4-81.2%). The percentage
decline in total AMH levels associated with maternal age (R = -0.53, p = 0.024),
but not with the women's first trimester AMH level. The postpartum total AMH
levels showed no consistent relationship to the woman's first trimester values
(range 31-273%). This raises the possibility that a fundamental determinant of
circulating AMH levels is reset during pregnancy. The ratio of proAMH to total
AMH levels exhibited little or no variation during pregnancy, indicating that the
control of the cleavage/activation of AMH is distinct from the mechanisms that
control the total level of AMH.
PMID- 27612038
TI - Oxidation in the complementarity-determining regions differentially influences
the properties of therapeutic antibodies.
AB - Therapeutic antibodies can undergo a variety of chemical modification reactions
in vitro. Depending on the site of modification, either antigen binding or Fc
mediated functions can be affected. Oxidation of tryptophan residues is one of
the post-translational modifications leading to altered antibody functionality.
In this study, we examined the structural and functional properties of a
therapeutic antibody construct and 2 affinity matured variants thereof. Two of
the 3 antibodies carry an oxidation-prone tryptophan residue in the
complementarity-determining region of the VL domain. We demonstrate the
differences in the stability and bioactivity of the 3 antibodies, and reveal
differential degradation pathways for the antibodies susceptible to oxidation.
PMID- 27612041
TI - Incidental unilateral and bilateral ductal carcinoma in situ encountered in the
surgical management of young male gynecomastia.
AB - BACKGROUND: The increased risk for malignant tumors associated with male
gynecomastia has been well established and many authors have reported cases of
concurrent gynecomastia and ductal carcinoma in situ (DCIS) in the same breast.
Synchronous bilateral breast cancer in association with gynecomastia is
exceptionally rare. We aim to report and evaluate the management outcome of 5
cases of gynecomastia associated with DCIS (1 bilateral and 4 unilateral).
METHODS: A retrospective database analysis of the surgical treatment outcome of
74 male patients who had gynecomastia was done. A bilateral subcutaneous nipple
preserving mastectomy approach was done to all. Histopathology reports were
reviewed. RESULTS: 74 patients diagnosed and treated for gynecomastia were
included. The incidence rate of gynecomastia in our hospital male patients was
0.17%. The mean age was 22 years, range 17-29 years. Five (6.76%) patients were
found in histopathology specimens to have DCIS, 1 patient (23 years old) had
bilateral DCIS of low grade, 4 patients had unilateral positive involvement, 3
had right breast DCIS, and 1 had left breast DCIS, and all were of low-grade
papillary subtype. The incidence of ductal carcinoma in situ among our series
gynecomastia patients was 6.76%. CONCLUSION: We conclude that gynecomastia is a
benign breast disease but recent reports had described malignant variants, mostly
DCIS, including 5 young males in our series. Therefore, regardless of the age
group, histopathological examination of the resected gynecomastia tissue should
be carefully done in all patients. Further evidence-based studies are needed to
investigate the optimum management of incidental DCIS in gynecomastia specimens.
PMID- 27612040
TI - Sunitinib alone or in combination with chemotherapy for the treatment of advanced
breast cancer: A systematic review and meta-analysis.
AB - INTRODUCTION: Sunitinib is an orally delivered tyrosine kinase inhibitor that
exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of
metastatic renal cell carcinoma. However, its efficacy for the treatment of
advanced breast cancer (ABC) remains controversial. Therefore, we performed this
systematic review and meta-analysis to synthesize evidence from published
randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in
combination with chemotherapy for the treatment of ABC. METHODS: We followed
PRISMA statement guidelines during the preparation of this systematic review and
meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge,
and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted
using relevant keywords. Studies were screened for eligibility and data were
extracted to an online data extraction form. Progression free survival (PFS) and
overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model
using generic inverse variance method. Objective response rate (ORR) and
complications were pooled as relative risk (RR) in a random effect model meta
analysis using Mantel-Haenzel method. RESULTS: Six RCTs, with a total sample size
of 2273 patients, met our eligibility criteria and were included in this meta
analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS
(HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to
1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib
in combination with chemotherapy did not show superiority to chemotherapy in
terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95%
CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination
with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically
significant P value (P = 0.03). CONCLUSIONS: Current evidence shows that
sunitinib, either alone or in combination with chemotherapy, has no clinical
benefit for patients with advanced breast cancer. However, previous studies did
not considered patient stratification and outcome assessment based on molecular
markers. In terms of safety, toxicity was common with sunitinib treatment.
PMID- 27612042
TI - Desmoid-type fibromatosis of the breast: A case report.
AB - Desmoid-type fibromatosis of the breast (also referred to as desmoid tumor or
aggressive fibromatosis) is exceedingly rare. Although it does not metastasize,
desmoid-type fibromatosisis is frequently locally aggressive. Recurrence is
common (up to 35%), even after presumed total excision of the primary tumor [1].
The breast is an unusual location for the development of this tumor, with
relatively few cases reported in the literature. We report a case of desmoid-type
fibromatosis in the breast in a 31-year-old female who presented with a four
month history of a palpable left breast mass. Her imaging was discordant, so she
underwent surgical excision of the mass. Multiple positive margins were present.
She underwent re-excision to the level of the sternum medially. Final pathology
showed a focally positive posterior margin, without muscle or fascial
involvement. The patient's case was discussed at the multidisciplinary tumor
board conference and no further intervention was recommended. To our knowledge,
this is the first case report in the literature in which negative margins were
unable to be achieved for desmoid tumors of the breast operatively.
PMID- 27612044
TI - Etiologic revelation and outcome of the surgical management of idiopathic
granulomatous mastitis; An Egyptian centre experience.
AB - INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory
condition that is confused with cancer. It usually affects women in child bearing
age. The exact aetiology and pathogenesis are still unknown, and the optimal
therapeutic modality has not yet been established. Treatment most frequently
includes Antibiotics, corticosteroids and immunosuppressant, surgical excision,
and even mastectomy. MATERIAL AND METHODS: We studied a thirty cases diagnosed
with IGM in our locality to find out the leading risk factors and the outcome of
our surgical approach which involves excision of the lesion in continuity with
duct system. Patients demographic data, history related to lactation and outcome
were recorded. RESULTS: All patients were parous women with history of previous
breast feeding for all kids. Twenty-six patients (86.66%) had a history of early
incomplete nursing care to the affected breast. After our surgical approach,
Twenty eight (93.3%) patients showed fast recovery with no detectable recurrences
in the median follow up period (18 months) with acceptable cosmoses. CONCLUSION:
History of breast feeding together with early failure of complete nursing from a
single breast is the most important risk factors for development of IGM in young
aged women. Surgery plays an important role in treating IGM, however, it should
be directed towards excision of the present mass (s) together with the
pathological and colonized duct system.
PMID- 27612043
TI - Correlation between the DNA methylation and gene expression of IGFBP5 in breast
cancer.
AB - BACKGROUND: The insulin-like growth factor binding protein5 (IGFBP5) is often
dysregulated in human cancers and considered neither a tumor suppressor nor an
oncogene. OBJECTIVE: We aim to examine the reason of the changeable gene
regulation of IGFBP5 in the case of methylation in breast cancer. METHODS: We
used methyl-specific polymerase (MSP) chain reaction to detect CpG methylation of
IGFBP5 promoter and exon-I in breast cancer and adjacent tissues. Gene expression
is evaluated by quantative polymerase chain reaction (qPCR). RESULTS: IGFBP5
methylation was detected in 24 of 58 (41%) and 54 of 56 (96.5%) promoter and exon
I site respectively in tumor tissues. In adjacent tissues 17 of 58 (29%) and 53
of 56 (96.5%) was methylated. IGFBP5 expression was higher estrogene receptor
(ER)(+) than ER(-) patients (p = 0.0549). Beside, we found a positive correlation
between the expression of IGFBP5 and G2 tumor grade (p = 0.0131). However, no
correlation was observed between IGFBP5 expression and age, menopause or the
presence of lymph node metastasis (p > 0.05). CONCLUSIONS: In summary, our
results showed that IGFBP5 promoter and exon-I methylation did not have any
differences between tumor and adjacent tissues so that IGFBP5 methylation did not
change IGFBP5 gene regulation in breast cancer. This is the first study
investigating the IGFBP5 gene methylation in breast cancer.
PMID- 27612045
TI - Direct integration of the inverse Radon equation for X-ray computed tomography.
AB - A new mathematical appoach using the inverse Radon equation for restoration of
images in problems of linear two-dimensional x-ray tomography is formulated. In
this approach, Fourier transformation is not used, and it gives the chance to
create the practical computing algorithms having more reliable mathematical
substantiation. Results of software implementation show that for especially for
low number of projections, the described approach performs better than standard X
ray tomographic reconstruction algorithms.
PMID- 27612046
TI - Submillisievert coronary CT angiography with adaptive prospective ECG-triggered
sequence acquisition and iterative reconstruction in patients with high heart
rate on the dual-source CT.
AB - PURPOSE: To assess the application value of submillisievert coronary CT
angiography (CCTA) in patients with a high heart rate (HR) acquired with adaptive
prospective ECG-triggered sequence acquisition and iterative reconstruction on
the secondary generation dual-source CT. MATERIALS AND METHODS: A total of 120
consecutive high-HR patients suspected with coronary artery disease underwent
CCTA and invasive coronary angiography (ICA) within two weeks. Patients were
randomly assigned into three groups: group A (n = 40), where the patients
underwent retrospectively ECG-triggered acquisition CCTA at 100 kVp; group B (n =
40), where the patients received adaptive prospective ECG-triggered sequence
acquisition at 100 kVp; and group C (n = 40), where the patients performed
adaptive prospective ECG-triggered sequence acquisition at 80 kVp with iterative
reconstruction. The mean CT values, signal noise ratios (SNR) and contrast noise
ratios (CNR) in the ascending aorta and coronary arteries of the three groups
were measured and compared. The image quality and radiation dose among the three
groups were compared. The consistency of displaying the coronary stenosis of each
group was assessed compared with the results of ICA as the gold standard.
RESULTS: There was no significant difference in gender, age and body mass index
(BMI) (all P > 0.05). The mean attenuations, SNRs and CNRs in the ascending aorta
and coronary artery were not significantly different between group A and group B
(P > 0.05). The mean attenuations of group C were significantly higher than group
A and group B (P < 0.01), but the image noise and CNR were significantly lower in
group C (P < 0.01). The number of appreciable segments among the three groups was
not significantly different on a per-segment and per-vessel basis (P > 0.05). The
subjective image quality among the three groups was not significantly different
(P > 0.05). With the ICA result as a reference standard, there was good
consistency in the evaluation of the coronary stenosis degree between CCTA and
ICA (r > 0.75), as well as in the assessment of the coronary stenosis rate using
the Bland- Altman analysis. The mean radiation dose in group B was half of that
in group A. Moreover, the mean radiation dose in group C was less than one sixth
of that in group A and less than 1 mSv (0.7+/-0.2 mSv). CONCLUSIONS: For patients
with high HR, adaptive prospective ECG-triggered sequence acquisition on the
FLASH dual-source CT results in equal image quality and half of the radiation
dose reduction compared with retrospectively ECG-triggered spiral acquisition at
the same tube voltage (100 kVp) and same R-R interval of exposure. In addition,
adaptive prospective ECG-triggered sequence acquisition combined with low tube
voltage and iterative reconstruction can further reduce the radiation dose to the
submillisievert level without compromising image quality and the accuracy of
assessing the coronary stenosis degree, and can be popularized as a routine
technique.
PMID- 27612047
TI - Fully 3D geometrical calibration for an X-ray grating-based imaging system.
AB - The Precision of geometric parameters is the key requirement for grating-based
phase-contrast CT and attenuation-based CT in cone-beam geometry. By extending
our fan-beam geometric calibration work via Locally Linear Embedding (LLE) into
the cone-beam case, here we calibrate the geometric parameters of our in-house
phase-contrast CT system with attenuation projection data. Numerical and
experimental studies show that the LLE-based calibration method is feasible to
calibrate 8 parameters of the cone-beam geometry that improves reconstruction
quality significantly.
PMID- 27612048
TI - Robust low-dose dynamic cerebral perfusion CT image restoration via coupled
dictionary learning scheme.
AB - Dynamic cerebral perfusion x-ray computed tomography (PCT) imaging has been
advocated to quantitatively and qualitatively assess hemodynamic parameters in
the diagnosis of acute stroke or chronic cerebrovascular diseases. However, the
associated radiation dose is a significant concern to patients due to its dynamic
scan protocol. To address this issue, in this paper we propose an image
restoration method by utilizing coupled dictionary learning (CDL) scheme to yield
clinically acceptable PCT images with low-dose data acquisition. Specifically, in
the present CDL scheme, the 2D background information from the average of the
baseline time frames of low-dose unenhanced CT images and the 3D enhancement
information from normal-dose sequential cerebral PCT images are exploited to
train the dictionary atoms respectively. After getting the two trained
dictionaries, we couple them to represent the desired PCT images as spatio
temporal prior in objective function construction. Finally, the low-dose dynamic
cerebral PCT images are restored by using a general DL image processing. To get a
robust solution, the objective function is solved by using a modified dictionary
learning based image restoration algorithm. The experimental results on clinical
data show that the present method can yield more accurate kinetic enhanced
details and diagnostic hemodynamic parameter maps than the state-of-the-art
methods.
PMID- 27612049
TI - Liver acquisition with acceleration volume acquisition gadolinium-enhanced
magnetic resonance combined with T2 sequences in the diagnosis of local
recurrence of rectal cancer.
AB - To investigate the efficacy of liver acquisition with acceleration volume
acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to
assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer
with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI,
including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1
weighted FSE with fat suppression, was performed on 225 patients with
postoperative rectal cancer. Two readers evaluated the presence of LR according
to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1
fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate
diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective
scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA
was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic
efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p =
0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for
Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR
increases the accuracy of diagnosis of LR from rectal cancer and could replace
conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow
up of rectal cancer.
PMID- 27612050
TI - A fast method based on NESTA to accurately reconstruct CT image from highly
undersampled projection measurements.
AB - BACKGROUND: The CT image reconstruction algorithm based compressed sensing (CS)
can be formulated as an optimization problem that minimizes the total-variation
(TV) term constrained by the data fidelity and image nonnegativity. There are a
lot of solutions to this problem, but the computational efficiency and
reconstructed image quality of these methods still need to be improved.
OBJECTIVE: To investigate a faster and more accurate mathematical algorithm to
settle TV term minimization problem of CT image reconstruction. METHOD: A
Nesterov's algorithm (NESTA) is a fast and accurate algorithm for solving TV
minimization problem, which can be ascribed to the use of most notably Nesterov's
smoothing technique and a subtle averaging of sequences of iterates, which has
been shown to improve the convergence properties of standard gradient-descent
algorithms. In order to demonstrate the superior performance of NESTA on
computational efficiency and image quality, a comparison with Simultaneous
Algebraic Reconstruction Technique-TV (SART-TV) and Split-Bregman (SpBr)
algorithm is made using a digital phantom study and two physical phantom studies
from highly undersampled projection measurements. RESULTS: With only 25% of
conventional full-scan dose and, NESTA method reduces the average CT number error
from 51.76HU to 9.98HU on Shepp-Logan phantom and reduces the average CT number
error from 50.13HU to 0.32HU on Catphan 600 phantom. On an anthropomorphic head
phantom, the average CT number error is reduced from 84.21HU to 1.01HU in the
central uniform area. CONCLUSIONS: To the best of our knowledge this is the first
work that apply the NESTA method into CT reconstruction based CS. Research shows
that this method is of great potential, further studies and optimization are
necessary.
PMID- 27612051
TI - An autotuning respiration compensation system based on ultrasound image tracking.
AB - The purpose of this study was to develop an ultrasound image tracking algorithm
(UITA) for extracting the exact displacement of internal organs caused by
respiratory motion. The program can track organ displacements in real time, and
analyze the displacement signals associated with organ displacements via a
respiration compensating system (RCS). The ultrasound imaging system is
noninvasive and has a high spatial resolution and a high frame rate (around 32
frames/s), which reduces the radiation doses that patients receive during
computed tomography and X-ray observations. This allows for the continuous
noninvasive observation and compensation of organ displacements simultaneously
during a radiation therapy session.This study designed a UITA for tracking the
motion of a specific target, such as the human diaphragm. Simulated diaphragm
motion driven by a respiration simulation system was observed with an ultrasound
imaging system, and then the induced diaphragm displacements were calculated by
our proposed UITA. These signals were used to adjust the gain of the RCS so that
the amplitudes of the compensation signals were close to the target movements.
The inclination angle of the ultrasound probe with respect to the surface of the
abdomen affects the results of ultrasound image displacement tracking. Therefore,
the displacement of the phantom was verified by a LINAC with different
inclination-angle settings of the ultrasound probe. The experimental results
indicate that the best inclination angle of the ultrasound probe is 40 degrees,
since this results in the target displacement of the ultrasound images being
close to the actual target motion. The displacement signals of the tracking
phantom and the opposing displacement signals created by the RCS were compared to
assess the positioning accuracy of our proposed ultrasound image tracking
technique combined with the RCS.When the ultrasound probe was inclined by 40
degrees in simulated respiration experiments using sine waves, the correlation
between the target displacement on the ultrasound images and the actual target
displacement was around 97%, and all of the compensation rates exceeded 94% after
activating the RCS. Furthermore, the diaphragm movements on the ultrasound images
of three patients could be captured by our image tracking technique. The test
results show that our algorithm could achieve precise point locking and tracking
functions on the diaphragm. This study has demonstrated the feasibility of the
proposed ultrasound image tracking technique combined with the RCS for
compensating for organ displacements caused by respiratory motion.This study has
shown that the proposed ultrasound image tracking technique combined with the RCS
can provide real-time compensation of respiratory motion during radiation
therapy, without increasing the overall treatment time. In addition, the system
has modest space requirements and is easy to operate.
PMID- 27612052
TI - Clinical surface modification process using the nitrogen plasma and its anti
bacterial efficiency.
AB - In this research, the cotton fabrics were treated with nitrogen plasma for the
clinical and anti-bacterial purposes. Turmeric was used a as a natural dye. Some
part of both untreated and plasma treated samples was immersed in silver nitrate
as a mordant before dyeing. Effect of plasma and silver nitrate on dye ability of
cotton samples was compared and studied. Samples were analyzed with different
experimental methods, such as scanning electron microscopy (SEM), Reflection
spectro-photometry and antibacterial test. Results showed that, turmeric dye have
anti-bacterial efficiency and good antibacterial activity achieved by plasma
treatment of fabrics. In case of AgNO3 treatment, samples showed 100%
antibacterial activity. It also concluded that, nitrogen plasma has synergic
effect on antibacterial activity of turmeric as natural dye on cotton fabrics.
PMID- 27612053
TI - A new metal artifact reduction algorithm based on a deteriorated CT image.
AB - BACKGROUND: Computed tomography (CT) is an established imaging technology
primarily used as a non-invasive diagnostic tool that reconstructs axial images.
However, significant problems with metal artifacts remain. A metal artifact is a
strong radial noise in an image, which makes it difficult to diagnose patients
and inspect products containing metal implants. Historically, studies related to
metal artifact reduction used projection data, though the data is not typically
saved after processing. OBJECTIVE: This study proposes a new metal artifact
reduction algorithm that does not require projection data, for new applications
and for accurate diagnostic techniques. METHODS: The algorithm utilizes
reconstructed images and is based on iterative reconstruction. By reproducing an
accurate forward projection on simulation and combining it with an iterative
calculation, discrepancies causing metal artifacts are eliminated. RESULTS:
Validation was completed with numerical phantom models. Our results indicate that
the proposed algorithm effectively reduces metal artifacts, even if numerous
complex-shaped metal pieces were embedded in the cross-section. CONCLUSIONS: We
developed a novel reconstruction algorithm for metal artifact reduction in CT
imaging that only requires reconstructed images and projection conditions. Any
historical CT data containing metal artifacts could be improved with this method.
PMID- 27612054
TI - Objective performance assessment of five computed tomography iterative
reconstruction algorithms.
AB - OBJECTIVE: Iterative algorithms are gaining clinical acceptance in CT. We
performed objective phantom-based image quality evaluation of five commercial
iterative reconstruction algorithms available on four different multi-detector CT
(MDCT) scanners at different dose levels as well as the conventional filtered
back-projection (FBP) reconstruction. METHODS: Using the Catphan500 phantom, we
evaluated image noise, contrast-to-noise ratio (CNR), modulation transfer
function (MTF) and noise-power spectrum (NPS). The algorithms were evaluated over
a CTDIvol range of 0.75-18.7 mGy on four major MDCT scanners: GE DiscoveryCT750HD
(algorithms: ASIRTM and VEOTM); Siemens Somatom Definition AS+ (algorithm:
SAFIRETM); Toshiba Aquilion64 (algorithm: AIDR3DTM); and Philips Ingenuity iCT256
(algorithm: iDose4TM). Images were reconstructed using FBP and the respective
iterative algorithms on the four scanners. RESULTS: Use of iterative algorithms
decreased image noise and increased CNR, relative to FBP. In the dose range of
1.3-1.5 mGy, noise reduction using iterative algorithms was in the range of 11%
51% on GE DiscoveryCT750HD, 10%-52% on Siemens Somatom Definition AS+, 49%-62% on
Toshiba Aquilion64, and 13%-44% on Philips Ingenuity iCT256. The corresponding
CNR increase was in the range 11%-105% on GE, 11%-106% on Siemens, 85%-145% on
Toshiba and 13%-77% on Philips respectively. Most algorithms did not affect the
MTF, except for VEOTM which produced an increase in the limiting resolution of up
to 30%. A shift in the peak of the NPS curve towards lower frequencies and a
decrease in NPS amplitude were obtained with all iterative algorithms. VEOTM
required long reconstruction times, while all other algorithms produced
reconstructions in real time. Compared to FBP, iterative algorithms reduced image
noise and increased CNR. CONCLUSIONS: The iterative algorithms available on
different scanners achieved different levels of noise reduction and CNR increase
while spatial resolution improvements were obtained only with VEOTM. This study
is useful in that it provides performance assessment of the iterative algorithms
available from several mainstream CT manufacturers.
PMID- 27612055
TI - Interior tomography with curvelet-based regularization.
AB - The interior problem, i.e. reconstruction from local truncated projections in
computed tomography (CT), is common in practical applications. However, its
solution is non-unique in a general unconstrained setting. To solve the interior
problem uniquely and stably, in recent years both the prior knowledge- and
compressive sensing (CS)-based methods have been developed. Those theoretically
exact solutions for the interior problem are called interior tomography. Along
this direction, we propose here a new CS-based method for the interior problem
based on the curvelet transform. A curvelet is localized in both radial and
angular directions in the frequency domain. A two-dimensional (2D) image can be
represented in a curvelet frame. We employ the curvelet transform coefficients to
regularize the interior problem and obtain a curvelet frame based regularization
method (CFRM) for interior tomography. The curvelet coefficients of the
reconstructed image are split into two sets according to their visibility from
the interior data, and different regularization parameters are used for these two
sets. We also presents the results of numerical experiments, which demonstrate
the feasibility of the proposed approach.
PMID- 27612056
TI - Relationship of aerobic fitness with cardiovascular risk factors in firefighters.
AB - BACKGROUND: Epidemiological studies on the general population have shown that
increased physical activity and aerobic fitness (AF) significantly decrease the
risk of coronary artery disease. Finding ways to decrease such risk factors can
promote the health of firefighters. METHODS: This study was conducted in a large
industrial facility in Tehran. AF assessment and submaximal aerobic fitness
testing of participants were performed according to the guidelines of the
American College of Sports Medicine (ACSM). AF was determined using a bicycle
ergometer. Other information was collected using a specifically designed
questionnaire, physical examination and blood test. Data were analyzed using
SPSS. Level of significance was set at P < 0.05. RESULTS: A total of 157 male
firefighters were evaluated in an industrial facility. The results of logistic
regression analysis revealed that AF was significantly correlated with age, body
mass index (BMI), cigarette smoking, physical activity, hemoglobin level, low
density lipoprotein (LDL) level, high-density lipoprotein (HDL) level, resting
systolic blood pressure (RSBP), diastolic blood pressure (RDBP) and heart rate
(RHR) (P < 0.05). CONCLUSIONS: Firefighters with greater AF had lower
cardiovascular disease (CVD) risk factors. Longitudinal studies are required to
further confirm this finding. Increasing the AF may decrease CVD risk factors in
firefighters.
PMID- 27612057
TI - Melatonin therapy in shift workers with difficulty falling asleep: A randomized,
double-blind, placebo-controlled crossover field study.
AB - BACKGROUND: Disturbed sleep is common in shift work. It is hypothesized that
administration of exogenous melatonin could reduce the sleep latency and improve
the sleep quality. OBJECTIVE: To evaluate the efficacy of 3 mg melatonin taken 30
min before night time sleep on shift workers with difficulty falling asleep.
METHODS: Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)
were applied to find out shift workers with difficulty falling asleep. A
randomized, double-blind, placebo-controlled crossover study with periods of 3
night and washouts of 2 weeks comparing melatonin with placebo was performed.
Night time sleep parameters obtained from somnowatch including total sleep time
(TST), sleep onset latency (SOL), sleep efficiency (SE) and wakening after sleep
onset (WASO) were analyzed. RESULTS: Among 295 workers, 103 had difficulty
falling asleep. Finally, from 50 randomly selected workers with difficulty
falling asleep, 39 workers completed the study. Melatonin treatment significantly
increased SE and decreased SOL in comparison with baseline and taking placebo. SE
was increased from 82.1% at baseline to 85.5% after melatonin therapy. Also SOL
was decreased from 0.27 h at baseline to 0.20 h after melatonin therapy. Effects
of Melatonin administration on TST and WASO were not significant. CONCLUSIONS:
This study showed that melatonin therapy in shift workers with difficulty falling
asleep significantly improved the sleep onset latency and sleep efficiency.
PMID- 27612058
TI - Is sheltered employment more stable than ordinary employment?
AB - BACKGROUND: Sheltered Employment Centres are a key component of policies
promoting the employment of people with disabilities in Spain. The firms involved
form a sort of 'protected' labour market for people with disabilities. Their
purpose is to provide employment opportunities for people with disabilities who
have difficulties entering the 'ordinary' labour market. OBJECTIVE: The aim in
this article is to analyse whether workers with disabilities enjoy greater
stability in sheltered employment centres than in ordinary firms. METHODS: Using
data from the Longitudinal Sample of Working Lives, which includes information
about the labour market trajectory of Spanish workers, survival models are
employed to analyse the duration of employment periods of workers with
disabilities. Workers in sheltered employment centres are compared to workers in
ordinary firms. RESULTS: Results confirm that employment in SECs is more stable
than in ordinary firms, even after controlling for the effects of other variables
such as sex, age, level of qualifications and characteristics of the firms.
CONCLUSIONS: Employment in SEC provides to workers with disability a more stable
career path with lower turnover than working in ordinary firms. More research is
needed to consider other working conditions such as wages and promotion
possibilities.
PMID- 27612059
TI - Effect of the craniocervical brace on craniocervical angle, thoracic kyphosis
angle, and trunk extensor muscle activity during typing in subjects with forward
head posture.
AB - BACKGROUND: The relationship between forward head posture (FHP) and thoracic
kyphosis has been a subject of interest in the rehabilitation field for visual
display terminal workers. OBJECTIVE: The aim of this study was to investigate the
immediate effects of the craniocervical brace use on craniocervical angle (CCA),
thoracic kyphosis angle (TKA), and trunk extensor muscle activity. METHODS:
Twelve young male subjects with forward head posture (21.6+/-1.9 years)
participated in this study. We compared CCA & TKA and trunk extensor muscle
activity between with and without application of the craniocervical brace during
visual display terminal work. RESULTS: When wearing the craniocervical brace, the
subjects demonstrated significantly greater CCA at the start and the end of the
task and less change in CCA during the task (p < 0.05). While non-significantly
less TKA was seen at the start of the task, significantly less TKA was observed
at the end of the task when using the craniocervical brace (p < 0.05). The
craniocervical brace use also led to significantly less change in TKA (p < 0.05).
There was no significant difference in the trunk extensor muscle activity.
CONCLUSIONS: Use of the craniocervical brace decreased FHP immediately, lessened
thoracic kyphosis over time, and prevented the worsening of FHP and thoracic
kyphosis during visual display terminal work.
PMID- 27612060
TI - Determinants and predictors of absenteeism and return-to-work in workers with
shoulder disorders.
AB - BACKGROUND: Shoulder disorders lead to substantial productivity loss and
determinants and predictors of sick leave are poorly known. OBJECTIVE: To perform
a systematic review on determinants and predictors of sick leave and delayed
return-to-work (RTW) in workers with shoulder disorders. METHODS: A systematic
literature search was conducted and we included studies on workers with shoulder
disorders that contained information on determinants or predictors for sick leave
or RTW, The risk of bias of included studies was evaluated with a validated tool.
RESULTS: Eight studies were included and four had a high risk of bias. The only
determinants that were found significantly associated with delayed RTW or
sickness absence in more than one study were an atraumatic history, disease
severity and previous sickness absence. A clinical prediction rule was developed
to predict sick leave in one study and included the following predictors: a
longer duration of sick leave prior to consultation, higher shoulder pain,
strain/overuse in usual activities and psychological complaints. CONCLUSION:
Several determinants or predictors were identified in the present review, but
there is currently inconsistent evidence on the role of any determinants or
predictors of work absence or delayed RTW for workers with a shoulder disorder.
More methodologically sound studies are needed.
PMID- 27612061
TI - Comparison of muscle activity of wrist extensors and kinematics of wrist joint
during wrist extension in automobile assembly line workers with and without
lateral epicondylitis.
AB - BACKGROUND: Overuse of the extensor carpi radialis (ECR) may play a role in the
development of lateral epicondylitis (LE). However, no studies have investigated
the muscle activity ratio between the ECR and extensor carpi ulnaris (ECU)
associated with the kinematics during wrist extension in workers with LE.
OBJECTIVE: We compared the ratio (ECR/ECU) of muscle activity between the ECR and
ECU and the kinematics of the wrist during wrist extension between workers with
and without LE. METHODS: Fifteen automobile assembly line workers with LE and 15
workers without LE participated in this study. The ratio of muscle activity was
measured using surface electromyography, and wrist kinematics were measured by a
three-dimensional motion analysis system while the workers extended their wrists
actively to the maximum range to which they did not feel uncomfortable. RESULTS:
Significantly greater ratios of muscle activity, ranges of radial deviation, and
combined motion of radial deviation and extension (CMDE) were shown in workers
with LE compared to those without LE. Also, the range of wrist extension was
significantly lower in workers with LE than in those without LE. CONCLUSIONS:
Quantifying the ratio of muscle activity with altered kinematics of wrist
extension may help researchers to understand why overuse of ECR is occurring and
explain LE development in automobile assembly line workers.
PMID- 27612062
TI - The meaning of employment from the perspective of persons with spinal cord
injuries in six European countries.
AB - BACKGROUND: People with spinal cord injuries (SCI) are underrepresented in the
labour force. OBJECTIVE: To examine the meaning of employment, as it is
understood in the context of participation and integration in society, among
persons with SCI in six European countries. We ask how SCI relates to employment,
for the functions of employment, alternatives to employment, and its obstacles.
METHOD: Semi-structured interviews were conducted with 74 persons and
qualitatively analysed using a grounded theory approach. RESULTS: Employment was
ranked as very important independent of the participants current employment
status. We identified three main functions of employment: 1) employment
contributes to the creation of personal and collective identity and social
recognition; 2) employment enables structuring of time and distracts from
impairment and pain; 3) employment is as an important social arena that
facilitates interaction with other people. Voluntary work and domestic work did
not fully replace the social functions of employment, nor correspond to the
design of the disability compensation systems. CONCLUSION: This study illustrates
the high value of employment and a need to pay more attention to a broader range
of productive work. It also reveals the interdependencies between employment
status and income mediated by the disability compensation schemes.
PMID- 27612063
TI - Association between upper extremity musculoskeletal disorders and mental health
status in office workers.
AB - BACKGROUND: Musculoskeletal Disorders (MSDs) can lead to potential adverse
consequences for individuals and their organizations, and in various research,
its relationship to physical and mental health of workforce has been studied.
OBJECTIVE: The purpose of this study was to determine the prevalence of MSDs of
upper extremities among office workers and its association with mental health
status. METHODS: In this cross sectional study, 1488 out of 1630 office workers
completed the Standardized Nordic Musculoskeletal Disorders Ques-tionnaire and
General Health Questionnaire (GHQ-28) (response rate = 91.3%). RESULTS: Upper
extremity MSDs were reported in 410 (27.5%) office workers, including 269 (18.1%)
shoulder, 79 (5.3%) elbow and 207 (13.9%) hand/wrist symptoms. Based on GHQ-28,
254 (17.1%) participants were found to be at risk of developing a psychiatric
disorder that were observed in 26.7% of workers with MSDs symptoms. Shoulder (p <
0.001), elbow (p < 0.001) and hand/wrist (p < 0.001) MSDs were associated with
poor mental health. Among the four GHQ-28 subscales (somatic symptoms,
anxiety/insomnia, social dysfunction, and depression), anxiety/insomnia was
strongly correlated with shoulders (P < 0.001), elbows (P = 0.002), and
hands/wrists (P < 0.001) symptoms. CONCLUSION: Office workers with upper
extremity MSDs were more likely to be experiencing mental distress. This
indicates a need for greater emphasis on preventive programs at workplace to
support their psychological well-being.
PMID- 27612064
TI - Participatory design of a social enterprise for rehabilitees.
AB - BACKGROUND: Social enterprises are often seen as a source of new and innovative
solutions to persistent societal problems and a means for better inclusion of
employees and customers. Because social enterprises combine business logic and
social goals, they have vast potential to renew business and social life;
therefore, it is vital to understand how their creation can be initiated and
supported. OBJECTIVE: This study provides an overview of the participatory design
process for a new social enterprise as it appears in practice. METHODS: The
methods used in this case study guided the participants - mental health and
substance abuse rehabilitees - in the co-creation and refinement of a business
idea. The methods used enabled participants to acknowledge their own strengths or
preferences for their potential future work, which was a unique means of
establishing a new social enterprise. RESULTS AND CONCLUSIONS: Social empowerment
of the participants/future employees of the social enterprise formed the
important, intangible capital in this case. By definition, the core of social
enterprises is the customer- and employee-driven nature. This study clarifies how
a social enterprise functions as a laboratory of social innovation at the local
and community levels.
PMID- 27612065
TI - Oxidative toxic stress in workers occupationally exposed to ceramic dust: A study
in a ceramic manufacturing industry.
AB - BACKGROUND: Exposure to compounds used in ceramic industries appears to be
associated with induction of oxidative toxic stress. OBJECTIVE: This cross
sectional study was undertaken to assess the oxidative toxic stress parameters
associated with occupational exposure to ceramic dust. METHODS: Forty ceramic
exposed workers from a ceramic manufacturing industry and 40 unexposed referent
subjects were studied. A questionnaire containing information regarding
demographic variables, occupational history, history of any chronic disease,
antioxidant consumption, and use of therapeutic drugs was administrated to them.
Oxidative toxic stress biomarkers including lipid peroxidation (LPO), total
antioxidant power (TAP), levels of total Thiol groups (TTG) and catalase (CAT)
activity were measured. RESULTS: Significant increments in blood LPO levels, CAT
activity and concomitant lower TAP were observed in ceramic exposed workers in
comparison to referent group. No statistically significant difference was noted
between the means of TTG levels between the groups. CONCLUSIONS: Findings of the
study indicate that occupational exposure to ceramic dust induces oxidative toxic
stress. Supplementation of workers with antioxidants may have beneficial effects
on oxidative damages in ceramic industries.
PMID- 27612066
TI - Rights, responsibilities and (re)presentation: Using drawings to convey health
and safety messages among immigrant workers.
AB - BACKGROUND: Immigrant workers who are new to Canada are considered a vulnerable
population under the Ontario Ministry of Labour Prevention Strategy for workplace
safety. Posters outlining workplace safety rights and responsibilities may not be
understandable to new immigrants. OBJECTIVE: To explore visual approaches to
making health and safety messages more understandable to new immigrants. METHODS:
This pilot study used arts-based qualitative research methods. Key messages from
the Ministry of Labour Health & Safety at Work poster were (re)represented as
images by an artist. Recent immigrants engaged in individual interviews and then
took part in a focus group, in order to elicit their experiences of health and
safety practices, their understanding and feedback concerning the Ministry
poster, and the images created. RESULTS: An image-rich version of the poster was
developed. The combination of drawings and minimal text was preferred and
considered helpful by participants. Barriers to health and safety and work
challenges for new immigrants were highlighted. Visual analysis yielded new
versions of the poster, as well as a pictorial representation of the research
process and study findings. CONCLUSIONS: The study demonstrates the value of
using image-rich posters with immigrant workers, and the effectiveness of using
arts-based methods within the research process.
PMID- 27612067
TI - Return to work after vocational rehabilitation for sick-listed workers with long
term back, neck and shoulder problems: A follow-up study of factors involved.
AB - BACKGROUND: Absence from work due to musculoskeletal disorders is a significant
problem from a number of perspectives, and there is a great need to identify
factors that facilitate return to work (RTW). OBJECTIVE: To identify factors
related to RTW after vocational rehabilitation for sick-listed workers with long
term back, neck and/or shoulder problems, and to compare the results with those
from a previous literature review based on studies from 1980 to 2000. METHODS: A
literature review based on studies published 2001-2014 in PubMed, CINAHL, EMBASE,
ERIC and the Cochrane Library. RESULTS: Major risk factors for not returning to
work are: higher age, factors related to pain such as higher levels of pain and
pain related fear, avoidance of activity, high distress and depression.
Facilitating factors for RTW are: lower functional disability, gaining control
over one's own condition, believing in RTW and work-related factors such as
occupational training, and having a job coach or an RTW coordinator. Compared
with the results from the previous review, the present review shows less of a
focus on sociodemographic factors and more on psychological factors. Both studies
highlight risk factors such as older age, higher levels of pain, depression and
less internal locus of control. CONCLUSION: Psychosocial and work-related factors
are important and should be included in interventions for the RTW of people with
long-term back, neck and/or shoulder problems.
PMID- 27612068
TI - Perceived social status among people with psychiatric disabilities attending work
oriented and meeting place-oriented day centers.
AB - BACKGROUND: Day centers have been criticized for giving attendees a lower social
status because they only offer activities that are often work-like although not
financially of benefit to attendees. OBJECTIVES: To explore day center attendees'
perceived social status and to identify associations among the attendees with the
center's orientation with activity, well-being, and psychiatric symptoms. METHOD:
Day center attendees in meeting place-oriented (n = 39) and work-oriented (n =
54) day centers in Sweden were interviewed addressing the targeted factors using
both self-rated and interview-based instruments. RESULT: Attendees rated
themselves close to the middle on the social status measure. No difference
between groups based on day center orientation was found. Their self-perceived
positioning on social status was positively related to the worker role,
occupational engagement, self-rated health, self-esteem, self-mastery, and
depressive symptoms. Logistic regression models showed better self-rated health
was the only predictor of belonging to the group with a higher level of social
status when dichotomized according to the median. Self-rated health was the
strongest indicator for scoring above the 75th percentile on perceived status,
followed by self-esteem, which was also a significant indicator. CONCLUSION:
These findings yielded new knowledge concerning perceived social status in the
target group and the importance of health and self-esteem.
PMID- 27612069
TI - Cultural events provided by employer and occupational wellbeing of employees: A
cross-sectional study among hospital nurses.
AB - BACKGROUND: Occupational well-being in health care is essential for the quality
of care and productivity. Some of the major challenges facing hospital nurses are
the personnel turnover, emotional loading and health care reforms. After primary
occupational safety and risk management, complementary positive health promotion
approaches with cultural interventions can be experimented. OBJECTIVE: To examine
the association between well-being indicators of hospital nurses and their
participation in cultural events provided by the employer (theater, concerts,
exhibitions, museums, sight-seeing, and musicals) during past 6 months. METHODS:
Subjective well-being was measured by work engagement, workplace support for new
ideas, work satisfaction and experienced stress. RESULTS: A dose-dependent
association was found between participation in cultural events and positive
psychology parameters of occupational well-being (support for new ideas and work
engagement), but the experience of stress was unrelated to participation in
cultural events. Collective participation has a positive covariant effect on work
engagement and seems to mediate the innovative work climate measured by workplace
support for new ideas. CONCLUSIONS: Collective cultural events for employees may
promote positive aspects of occupational wellbeing.
PMID- 27612070
TI - Does a prototype 'Experimental' chair facilitate more postural changes in
computing adolescents compared to a normal school chair?
AB - BACKGROUND: Prolonged sitting, such as when computing, has been linked to
adolescent spinal pain. A chair should fit the user's body dimensions and aid the
user in frequently changing sitting posture, rather than support one 'ideal'
posture. Such a chair is not currently available to high school learners.
OBJECTIVES: To develop a novel experimental school chair. To determine whether
the experimental chair encourages regular small range movement in all directions
whilst students work at computers in class. To compare the number of postural
changes between the normal static school chair and the experimental chair, whilst
students do computing work. METHODS: A development and validation study was
conducted. Twelve high school students were randomly selected from a conveniently
selected school. Fifteen minutes of 3D posture measurements were collected in
both the prototype and school computer chair. The analysis focused on the
frequency of postural movement. RESULTS: Data of eleven learners were analysed.
There were statistically significant increases in the number of postural changes
on the 'Experimental' chair compared to the school chair, for both pelvic side
flexion and pelvic rotation (rho= 0.01). CONCLUSION: The experimental chair
provided more postural movements when compared to the school computer chair.
Future studies should use this experimental chair to determine the effect of
increased postural movement, of especially the pelvis, on the prevalence and
intensity of musculoskeletal symptoms of high school learners in the Cape
Metropole area, Western Cape, South Africa.
PMID- 27612071
TI - Linking safety climate perception to types of behavior.
AB - BACKGROUND: Certain behavior types can drive the emergence of an unsafe act at
the workplace which may be reflected by workers' perceptions toward safety
climate. OBJECTIVE: The purpose of this study was to explore the relationship
between workers' safety climate perceptions (NOSACQ-50 questionnaire) and their
behavior types (based on DISC personality traits: Dominance, Influence,
Steadiness, and Conscientiousness). METHODS: NOSACQ-50 and DISC assessment
questionnaires were distributed on employees of four different companies (N =
755) working at hazardous workplaces in different occupational fields:
fertilizer, coal mining, and oil & gas. RESULTS: Four of the 48 correlation
coefficients were statistically significant in which the strongest correlation
was found between safety commitment and Influence (I) trait in public self (r =
0.119, p < 0.01). There were two groups of DISC's profile that have a lower
perception toward safety climate. The first group was indicated by high scores on
Influence (I) trait in public self (17.2% of respondents), and the latter was
characterized by low scores on Dominance (D) trait and high scores on
Conscientiousness (C) trait in private self (2.8% of respondents). CONCLUSIONS:
Lower perception toward safety climate was found to be correlated with two groups
of DISC's profile. Workers characterized with these two profiles are considered
to have priority needs for training or to be assigned to less a hazardous
workplace.
PMID- 27612072
TI - From the Editor.
PMID- 27612073
TI - Oral Infections and Cytokine Levels in Patients with Alzheimer's Disease and Mild
Cognitive Impairment Compared with Controls.
PMID- 27612075
TI - Issue dedicated to Dr Linda Michaud.
PMID- 27612076
TI - Children with Medical Complexity (CMC) Offer Challenges and Opportunities for the
Healthcare System.
PMID- 27612077
TI - The prevalence, location, severity, and daily impact of pain reported by youth
and young adults with cerebral palsy.
AB - PURPOSE: To describe the prevalence, location, severity, and daily impact of pain
reported by youth and young adults with cerebral palsy (CP). A secondary aim was
to identify any significant associations between the constructs of interest.
METHOD: An observational study of 112 participants with CP to understand their
experience of pain through a questionnaire. Participants were 56 males and 55
females with a mean age of 18y 9mo (SD 4y 5mo). RESULTS: Pain was reported by 75%
of males and 89% of females. Both severity and impact of pain were significantly
greater in females. In addition, severity and impact of pain were significantly
different between specific GMFCS levels. There were no significant differences in
location of pain by gender or GMFCS level. A strong positive correlation between
the severity and impact of pain was observed (rs = 0.80). CONCLUSION: The gender
differences in the severity and impact of pain and the overall and high
prevalence of pain reported here provide healthcare practitioners with an
increased awareness of pain distribution/characteristics among young adults with
CP. Understanding the impact of pain on daily life can assist practitioners to
efficiently manage pain and improve the quality of life for individuals with CP.
PMID- 27612078
TI - Correlating early motor skills to white matter abnormalities in preterm infants
using diffusion tensor imaging.
AB - PURPOSE: Diffusion tensor imaging (DTI) can detect injury to specific white
matter (WM) tracts involved with sensorimotor processing and may provide
sensitive measures for latent or nascent motor skills. We hypothesized that DTI
measures of WM fractional anisotropy (FA) could predict early motor scores on a
standardized assessment in a cohort of preterm infants at risk for WM injury.
METHODS: In this prospective study, preterm infants (n= 26, 11 female, 15 male,
mean gestational age 29.1 +/- 2.5) underwent the Test of Infant Motor Performance
(TIMP) at term and at 12 weeks corrected age (CA) and underwent an non-sedated
magnetic resonance imaging (MRI) with DTI at a mean of 42 +/- 1.5 weeks CA.
Fractional anisotropy (FA) was measured by Voxelwise statistical analysis using
Tract-Based Spatial Statistics (TBSS) in the specific regions of interest.
RESULTS: Significant differences were found between infants with poor versus
average performance on motor assessments at 12-weeks and FA values in several
left hemispheric WM tracts (p< 0.05). High FA of the left anterior limb of the
internal capsule (ALIC) predicted mean increase in TIMP scores on specific items
for head lift in prone and head lift turn to sound (p= 0.045 and p= 0.002).
CONCLUSION: Subtle WM injury, as indicated by low FA in left WM tracts, can
predict outcomes of early motor skills performance testing at 3 months. Early DTI
may identify infants with silent WM injury who need early intervention. Further
studies may establish if individual tract FA improve after targeted treatment.
PMID- 27612079
TI - The effect of supported physical activity on parental-reported sleep qualities
and pain severity in children with medical complexity.
AB - PURPOSE: To study the impact of a 5-week supported physical activity (PA)
intervention on parental report of sleep qualities, sleep duration, and pain
severity in children with medical complexity (CMC). METHODS: Twenty-nine CMC
participated in 180 minutes of daily supported PA on weekdays over 5 weeks. A pre
and post-test design was used to collect sleep qualities (Children's Sleep
Habits Questionnaire) and pain severity (Faces Pain Scale- Revised) as reported
by parents. Using a repeated measures design, weekly sleep diaries captured sleep
duration. RESULTS: Children with medical complexity experienced no adverse
effects, including pain, with the supported PA intervention. Significant
improvements in sleep problems, sleep duration, and pain severity (P< 0.05) were
demonstrated. CONCLUSION: Short-term supported PA did not interfere with sleep or
pain in CMC, and in fact, seems to have enhanced parental report of sleep
qualities, sleep duration, and pain severity. Supported PA appears safe for CMC
and healthcare professionals should explore methods to expand opportunities for
supported PA participation.
PMID- 27612080
TI - Serial casting for elbow flexion contractures in neonatal brachial plexus palsy.
AB - PURPOSE: The objective of this study was to evaluate the effectiveness of serial
casting of elbow flexion contractures in neonatal brachial plexus palsy. METHODS:
A prospective consecutive cohort study was performed with a median follow-up of 5
years. Forty-one patients with elbow flexion contractures >= 30 degrees were
treated with serial casting until the contracture was <= 10 degrees , for a
maximum of 8 weeks. Range of motion, number of recurrences and patient
satisfaction were recorded and analyzed using Wilcoxon signed-rank and Cox
regression tests. RESULTS: Passive extension increased from a median of -40
degrees (IQR -50 to -30) to -15 degrees (IQR -10 to -20, p < 0.001). Twenty
patients showed 37 recurrences. The baseline severity of passive elbow extension
had a hazard ratio of 0.93 (95% CI 0.89 to 0.96, p < 0.001) for first recurrence.
Median patient satisfaction was moderate. Four patients showed loss of flexion
mobility and in two patients serial casting had to be prematurely replaced by
night splinting due to complaints. CONCLUSION: Serial casting improved elbow
flexion contractures, although recurrences were frequent. The severity of elbow
flexion contracture is a predictor of recurrence. We recommend more research on
muscle degeneration and determinants involved in elbow flexion contractures to
improve treatment strategies and prevent side-effects.
PMID- 27612081
TI - Responsiveness of the Pediatric Evaluation of Disability Inventory-Computer
Adaptive Test in measuring functional outcomes for inpatient pediatric
rehabilitation.
AB - PURPOSE: Responsiveness of the PEDI-CAT Mobility, Daily Activities, and
Social/Cognitive domains and Wheelchair subdomain was evaluated for youth
admitted to a pediatric post-acute care hospital. METHODS: Inpatients ages 2-21
years, with a length of stay of >= 5 days and with both admission and discharge
scores were included. The difference between mean admission and discharge PEDI
CAT scaled scores were analyzed using paired t-tests. Effect sizes, standard
response means (SRMs), and minimal detectable change values were calculated.
Score comparison between diagnostic subgroups (Traumatic Brain Injury,
Neurological, Orthopedic, Medical) and age groups ( <= 5, > 5 but < 13, >= 13
years) were evaluated for the Mobility domain. RESULTS: Sample size differed by
domain with 66 Mobility, 30 Daily Activities, 19 Social/Cognitive and 9
Wheelchair subdomain pairs. Significant differences were found for all domains
when mean admission and discharge scaled scores were compared. Moderate to large
effect sizes and SRMs were found for the Mobility and Daily Activities domains
and Wheelchair subdomain. Small effect size but large SRM was found for the
Social/Cognitive domain. The Mobility domain was also responsive to changes in
all diagnostic and age groups. CONCLUSION: The PEDI-CAT was responsive to
functional changes for youth discharged from an inpatient pediatric
rehabilitation hospital.
PMID- 27612082
TI - Identification of ADHD in youth with epilepsy.
AB - PURPOSE: To further characterize Attention-Deficit/Hyperactivity Disorder (ADHD)
in a clinic-referred sample of youth with epilepsy. METHODS: Children and
adolescents with epilepsy who were referred for comprehensive neuropsychological
evaluation comprised the sample. Data were obtained via archival record review.
Youth with epilepsy were grouped according to ADHD diagnosis (no ADHD, ADHD -
Combined Type, and ADHD - Predominantly Inattentive Type) and compared for a
number of neurocognitive variables, seizure-related variables, and parent and
teacher completed behavior rating scale variables. Data was examined via analysis
of variance and logistic regression models with post hoc pairwise comparisons,
employing Tukey procedure where appropriate. RESULTS: Youth in this clinical case
series (N = 204) demonstrated a high rate of ADHD diagnosis. ADHD - Combined Type
was identified with slightly greater frequency than ADHD - Predominantly
Inattentive Type. Age of seizure onset, seizure classification, and seizure
frequency did not differ significantly between the groups. The groups also did
not differ on most cognitive variables examined. Significant group differences
were found for parent and teacher completed behavior rating scales assessing
inattention, hyperactivity, and executive dysfunction. CONCLUSION: Screening for
ADHD in youth with epilepsy is important as these symptoms can significantly
interfere with rehabilitative efforts. Behavior rating scales may be the most
efficient and cost effective way to identify ADHD in youth with epilepsy.
PMID- 27612083
TI - Predicting motor outcomes with 3 month prone hip angles in premature infants.
AB - PURPOSE: This study used kinematic analysis to identify a reliable and rapid
assessment method for abnormal patterns of motor development in preterm infants.
METHODS: In a retrospective analysis, we examined video of n= 35 preterm infants
at 3mo corrected age (CA) who had concurrent Test of Infant Motor Performance
(TIMP) scores. Hyperflexion at the hip produces common gait anomalies seen in
children with CP, therefore we analyzed hip angle in the prone head lift position
at 3 months CA. Magnetic Resonance Spectroscopy (MRS) was performed at term
equivalent (n= 23) and Bayley-III neurodevelopmental tests were performed at 1
year (n= 28). We correlated hip angles with TIMP and Bayley-III scores, and MRS
neuronal metabolites. RESULTS: Hip angle positively correlated with TIMP at 3
months (r= 0.642, p<= 0.001), but not with Bayley-III at 1 year (r= 0.122, p=
0.529). Hip angle correlated negatively with myo-inositol (mI) ratios in frontal
white matter tracts (mI/Cr r= -0.520, p= 0.011). CONCLUSIONS: These results
suggest prone hip angle may be a quantitative proxy for the 42-item TIMP at 3
months, and that hypertonicity in the hip flexor musculature is a manifestation
of white matter metabolic abnormalities (elevated mI ratios) that may indicate
occult white matter injury.
PMID- 27612084
TI - Implementing school based telehealth for children with medical complexity.
AB - PURPOSE: This quality improvement project aimed to improve parental experiences
with healthcare delivery and collaborative health care offered at a school
serving children with medical complexity (CMC) by implementing telehealth
services. METHODS: Parents of students at an urban public charter school for CMC
were surveyed before and after telehealth was implemented at the school for two
months, and again one year later, using the Measure of Processes of Care (MPOC
20). RESULTS: Parental scores on the MPOC-20 were generally high both before and
after the implementation of telehealth. There were no significant differences in
the scores. Anecdotally, parent satisfaction with telehealth services was high. A
review of the utilization of school-based telehealth during the 2015-2016 school
year among 13 schools, including this unique school for CMC, revealed that the
odds of having a telehealth visit at the school for CMC vs the other 12 schools
was 23.8 (p value < 0.001; CL:11.2 to 50.6). CONCLUSION: Parental experiences
with healthcare delivery were high both before and after the implementation of
telehealth at an urban public charter school for CMC. Utilization of telehealth
at the school for CMC was significantly higher than that of children enrolled in
the program at 12 other schools. Further research is needed to evaluate parental
experiences with school-based telehealth services.
PMID- 27612086
TI - Foundation for Physical Medicine & Rehabilitation announces 2016 winners of the
Gabriella E. Molnar-Swafford Pediatric PM&R Awards.
PMID- 27612085
TI - Energy expenditure during standing in children with cerebral palsy: A brief
report1.
AB - PURPOSE: The aim of the study was to estimate the energy expenditure (EE) during
a quiet standing task in children with bilateral spastic CP (BSCP) in comparison
with typically developing (TD) children, using gas analyzer. METHODS: The study
was an observational cross-sectional study of children with BSCP (Gross Motor
Function Classification System [GMFCS] levels II and III; n = 30; 10 males, 20
females; mean weight 27.46 kgs; mean age 10 years) and TD children (n = 30; 16
males, 14 females; mean weight 25.35 kgs; mean age 9 years, 9 months). The energy
expenditure during quiet standing task was measured by using Cosmed K4b2 gas
analyzer and expressed in terms of peak oxygen consumption (VO2 max, ml/kg body
weight/min). RESULTS: Children with BSCP expended 1.4 times higher energy during
standing than TD children (p< 0.0001). CONCLUSION: We identified that standing
puts an additional energy demand in ambulant children with BSCP. Findings suggest
that both dependant and independent ambulating children with BSCP might need to
exert more effort to maintain a static standing position. Therefore, clinicians
must evaluate standing position for balance control and energy expenditure to
evaluate the efficiency of physical therapy and rehabilitation.
PMID- 27612089
TI - Transforming your service: the right evidence at the right time and place.
AB - This virtual issue is published to coincide with the CILIP Health Libraries Group
Conference 2016. The theme of the conference is Knowledge for Healthcare (KFH),
the development framework for health care library and knowledge services (LKS),
published by Health Education England. Transforming the service, and delivering
the right evidence at the right time and place, is a key strategic focus of KFH.
Therefore, this virtual issue draws on content published in Health Information
and Libraries Journal (HILJ) in the last 2 years, which demonstrate initiatives
in health care LKS in line with the transformation strands outlined in KFH. The
virtual issue follows the same structure as a regular issue of HILJ, containing
one review article, a series of original articles and our three regular features:
Dissertations into Practice, Teaching and Learning in Action and International
Perspectives and Initiatives.
PMID- 27612088
TI - Unaltered Angiogenesis-Regulating Activities of Platelets in Mild Type 2 Diabetes
Mellitus despite a Marked Platelet Hyperreactivity.
AB - Type 2 diabetes mellitus (T2DM) is associated with platelet dysfunction and
impaired angiogenesis. Aim of the study is to investigate if platelet dysfunction
might hamper platelet angiogenic activities in T2DM patients. Sixteen T2DM
patients and gender/age-matched non-diabetic controls were studied. Flow
cytometry and endothelial colony forming cell (ECFC) tube formation on matrigel
were used to assess platelet reactivity and angiogenic activity, respectively.
Thrombin receptor PAR1-activating peptide (PAR1-AP) induced higher platelet P
selectin expression, and evoked more rapid and intense platelet annexin V binding
in T2DM patients, seen as a more rapid increase of annexin V+ platelets (24.3+/
6.4% vs 12.6+/-3.8% in control at 2 min) and a higher elevation (30.9+/-5.1% vs
24.3+/-3.0% at 8 min). However, PAR1-AP and PAR4-AP induced similar releases of
angiogenic regulators from platelets, and both stimuli evoked platelet release of
platelet angiogenic regulators to similar extents in T2DM and control subjects.
Thus, PAR1-stimulated platelet releasate (PAR1-PR) and PAR4-PR similarly enhanced
capillary-like network/tube formation of ECFCs, and the enhancements did not
differ between T2DM and control subjects. Direct supplementation of platelets to
ECFCs at the ratio of 1:200 enhanced ECFC tube formation even more markedly,
leading to approximately 100% increases of the total branch points of ECFC tube
formation, for which the enhancements were also similar between patients and
controls. In conclusion, platelets from T2DM subjects are hyperreactive. Platelet
activation induced by high doses of PAR1-AP, however, results in similar releases
of angiogenic regulators in mild T2DM and control subjects. Platelets from T2DM
and control subjects also demonstrate similar enhancements on ECFC angiogenic
activities.
PMID- 27612090
TI - CXCR7/p-ERK-Signaling Is a Novel Target for Therapeutic Vasculogenesis in
Patients with Coronary Artery Disease.
AB - Coronary artery disease (CAD) is characterized by insufficient vasculogenic
response to ischemia, which is typically accompanied by dysfunction of
endothelial outgrowth cells (EOCs). CXC chemokine receptor 7 (CXCR7) is a key
modulator of the neovascularization of EOCs to perfusion defect area. However,
the mechanism underlying the role of EOCs in CAD-related abnormal vasculogenesis
is still not clear. Here, we investigated the alteration of EOCs-related
vasculogenic capacity in patients with CAD and its potential mechanism. Compared
with EOCs isolated from healthy subjects, EOCs from CAD patients showed an
impaired vasculogenic function in vitro. CXCR7 expression of EOCs from CAD
patients was downregulated. Meanwhile, the phosphorylation of extracellular
signal-regulated kinase (ERK), downstream of CXCR7 signaling, was also reduced.
CXCR7 expression introduced by adenovirus increased the phosphorylation of ERK,
which was parallel to improved function of EOCs. The enhanced adhesion and
vasculogenesis of EOCs can be blocked by short interfering RNA (siRNA) against
CXCR7 and ERK inhibitor PD098059. Therefore, our study demonstrates that the
upregulation of CXCR7 signaling contributes to increased vasculogenic capacity of
EOCs from CAD patients, indicating that CXCR7 signaling may be a novel
therapeutic vasculogenic target for CAD.
PMID- 27612092
TI - Plasmonic nanoantenna hydrophones.
AB - Ultrasound is a valuable biomedical imaging modality and diagnostic tool. Here we
theoretically demonstrate that a single dipole plasmonic nanoantenna can be used
as an optical hydrophone for MHz-range ultrasound. The nanoantenna is tuned to
operate on a high-order plasmon mode, which provides an increased sensitivity to
ultrasound in contrast to the usual approach of using the fundamental dipolar
plasmon resonance. Plasmonic nanoantenna hydrophones may be useful for ultrasonic
imaging of biological cells, cancer tissues or small blood vessels, as well as
for Brillouin spectroscopy at the nanoscale.
PMID- 27612093
TI - Networked Spin Cages: Tunable Magnetism and Lithium Ion Storage via Modulation of
Spin-Electron Interactions.
AB - A networked spin cage comprising infinite CoII6L4 cages arrays (where Co =
Co(NCS)2 and L = 1,3,5-tri-(4-pyridyl)-verdazal radical) is synthesized and found
to exhibit tunable magnetic and electrochemical properties via inclusion of
guests. SQUID investigation reveals the coexistence of ferromagnetic and anti
ferromagnetic interactions between the Co(II) ion center and radical ligands.
Inclusion of electron-deficient guests (e.g., tetracyanoethylene) dramatically
enhances spin concentration and increases anti-ferromagnetic interactions due to
the formation of charge-transfer complex between the host and the guest. In
addition, introduction of electron-rich guests (e.g., tetrathiafulvalene) into
the networked spin cages doubles the capacity for binding the lithium ions.
PMID- 27612091
TI - Isolation and characterization of mutants corresponding to the MENA, MENB, MENC
and MENE enzymatic steps of 5'-monohydroxyphylloquinone biosynthesis in
Chlamydomonas reinhardtii.
AB - Phylloquinone (PhQ), or vitamin K1 , is an essential electron carrier (A1 ) in
photosystem I (PSI). In the green alga Chlamydomonas reinhardtii, which is a
model organism for the study of photosynthesis, a detailed characterization of
the pathway is missing with only one mutant deficient for MEND having been
analyzed. We took advantage of the fact that a double reduction of plastoquinone
occurs in anoxia in the A1 site in the mend mutant, interrupting photosynthetic
electron transfer, to isolate four new phylloquinone-deficient mutants impaired
in MENA, MENB, MENC (PHYLLO) and MENE. Compared with the wild type and
complemented strains for MENB and MENE, the four men mutants grow slowly in low
light and are sensitive to high light. When grown in low light they show a
reduced photosynthetic electron transfer due to a specific decrease of PSI. Upon
exposure to high light for a few hours, PSI becomes almost completely inactive,
which leads in turn to lack of phototrophic growth. Loss of PhQ also fully
prevents reactivation of photosynthesis after dark anoxia acclimation. In silico
analyses allowed us to propose a PhQ biosynthesis pathway in Chlamydomonas that
involves 11 enzymatic steps from chorismate located in the chloroplast and in the
peroxisome.
PMID- 27612094
TI - Gold-Catalyzed cis-Hydroarylation of Ynamides with Indoles: Regio- and
Stereoselective Synthesis of a Class of 2-Vinylindoles.
AB - A new gold-catalyzed reaction of ynamides with 3-substituted indoles as
nucleophiles is reported. The reaction allows for the synthesis of a new class of
2-vinylindole derivatives in good yields via the intermediacy of a cyclopropyl
gold-carbenoid species.
PMID- 27612095
TI - Epidemiologic and Spatiotemporal Characterization of Influenza and Severe Acute
Respiratory Infection in Uganda, 2010-2015.
AB - RATIONALE: Little is known about the epidemiology of severe acute respiratory
infection (SARI) or influenza in sub-Saharan Africa. Characterization of
influenza transmission dynamics and risk factors for severe disease and mortality
is critical to inform prevention and mitigation strategies. OBJECTIVES: To
characterize the epidemiology and transmission dynamics of influenza and risk
factors for influenza-associated severe respiratory infection in Uganda. METHODS:
Clinicians at 12 sentinel surveillance sites prospectively collected clinical
data and upper respiratory tract samples from consecutive patients who met
criteria for SARI and influenza-like illness (ILI). Samples were tested for
influenza A and B viruses using real-time reverse transcription-polymerase chain
reaction. Spatial and spatiotemporal cluster modeling was performed to identify
loci of increased influenza transmission. Morbidity and mortality were assessed
through chart review in a defined subset of patients. Univariable and
multivariable analyses were used to identify risk factors for severe respiratory
infection, prolonged hospitalization, and in-hospital mortality. MEASUREMENTS AND
MAIN RESULTS: From October 2010 to June 2015, 9,978 patients met case definitions
for SARI and ILI and had samples tested for influenza A and B. Of the 9,978
patient samples tested, 1,113 (11.2%) were positive for influenza. Among 6,057
patients with ILI, 778 samples (12.8%) were positive, and among 3,921 patients
with SARI, 335 samples (8.5%) were positive. Significant clustering of influenza
cases was observed in urban and periurban areas and during rainy seasons. Among
1,405 cases of SARI with available outcome data, in-hospital mortality was 1.6%.
Infection with the 2009 pandemic A/H1N1 subtype and prolonged time to
presentation were independently associated with SARI among influenza cases.
CONCLUSIONS: Influenza is associated with a substantial proportion of acute
respiratory infection in Uganda. As influenza vaccination programs are developed
in East Africa, timing campaigns to confer protection during rainy seasons should
be considered, particularly among high-risk urban populations.
PMID- 27612098
TI - Preparation of chiral oxazolinyl-functionalized beta-cyclodextrin-bonded
stationary phases and their enantioseparation performance in high-performance
liquid chromatography.
AB - A simple procedure for the synthesis of three new oxazolinyl-substituted beta
cyclodextrins (6-deoxy-6-R-(-)-4-phenyl-4,5-dihydrooxazolinyl-beta-cyclodextrin,
6-deoxy-6-S-(-)-4-phenyl-4,5-dihydrooxazolinyl-beta-cyclodextrin, and 6-deoxy-6-S
(-)-(4-pyridin-1-ium-4-methyl-benzenesulphonate)-4,5-dihy-drooxazolinyl-beta
cyclodextrin) and their covalent bonding to silica are reported. The ability of
these chiral stationary phase columns for separating compounds is also presented
and discussed. Twenty-eight compounds were examined in the polar-organic mobile
phase mode, and 11 beta-nitroethanols were tested in the reversed-phase mode.
Excellent enantioseparations were achieved for most of the analytes, even for
several challenging compounds. The rigid and flexible structures of mono
substituted chiral groups and the fragments around the rim of the beta
cyclodextrin cavity played an important role in the separation process. Factors
such as pi-pi stacking, dipole-dipole interactions, ion-pairing, and steric
hindrance effects were found to affect the chromatographic performance. Moreover,
the buffer composition, and percentages of organic modifiers in the mobile phase,
were investigated and compared. The mechanisms involved in the separation were
postulated based on the chromatographic data.
PMID- 27612097
TI - Divergent evolution of multiple virus-resistance genes from a progenitor in
Capsicum spp.
AB - Plants have evolved hundreds of nucleotide-binding and leucine-rich domain
proteins (NLRs) as potential intracellular immune receptors, but the evolutionary
mechanism leading to the ability to recognize specific pathogen effectors is
elusive. Here, we cloned Pvr4 (a Potyvirus resistance gene in Capsicum annuum)
and Tsw (a Tomato spotted wilt virus resistance gene in Capsicum chinense) via a
genome-based approach using independent segregating populations. The genes both
encode typical NLRs and are located at the same locus on pepper chromosome 10.
Despite the fact that these two genes recognize completely different viral
effectors, the genomic structures and coding sequences of the two genes are
strikingly similar. Phylogenetic studies revealed that these two immune receptors
diverged from a progenitor gene of a common ancestor. Our results suggest that
sequence variations caused by gene duplication and neofunctionalization may
underlie the evolution of the ability to specifically recognize different
effectors. These findings thereby provide insight into the divergent evolution of
plant immune receptors.
PMID- 27612096
TI - Indole-3- carbinol enhances sorafenib cytotoxicity in hepatocellular carcinoma
cells: A mechanistic study.
AB - Sorafenib is the only chemotherapeutic agent currently approved for unresectable
hepatocellular carcinoma (HCC). However, poor response rates have been widely
reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical.
The present study aimed to explore the potential chemomodulatory effects of I3C
on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C
exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p <
0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was
more effective (p = 0.002). Accordingly, subsequent mechanistic studies were
carried on HepG2 cells. The results show that the ability of I3C to enhance
sorafenib cytotoxicity in HCC cells could be partially attributed to increasing
the apoptotic activity and decreasing the angiogenic potentials. The combination
had a negative effect on epithelial-mesenchymal transition (EMT). Increased NOX-1
expression was also observed which may indicate the involvement of NOX-1 in I3C
chemomodulatory effects. Additionally, the combination induced cell cycle arrest
at the G0/G1 phase. In conclusion, these findings provide evidence that I3C
enhances sorafenib anti-cancer activity in HCC cells.
PMID- 27612099
TI - Modification of sigma-Donor Properties of Terminal Carbide Ligands Investigated
Through Carbide-Iodine Adduct Formation.
AB - The terminal carbide ligands in [(Cy3 P)2 X2 Ru=C] complexes (X=halide or
pseudohalide) coordinate molecular iodine, affording charge-transfer complexes
rather than oxidation products. Crystallographic and vibrational spectroscopic
data show the perturbations of iodine to vary with the auxiliary ligand sphere on
ruthenium, demonstrating the sigma-donor properties of carbide complexes to be
tunable.
PMID- 27612100
TI - On the Orientation Error of IMU: Investigating Static and Dynamic Accuracy
Targeting Human Motion.
AB - The accuracy in orientation tracking attainable by using inertial measurement
units (IMU) when measuring human motion is still an open issue. This study
presents a systematic quantification of the accuracy under static conditions and
typical human dynamics, simulated by means of a robotic arm. Two sensor fusion
algorithms, selected from the classes of the stochastic and complementary
methods, are considered. The proposed protocol implements controlled and
repeatable experimental conditions and validates accuracy for an extensive set of
dynamic movements, that differ in frequency and amplitude of the movement. We
found that dynamic performance of the tracking is only slightly dependent on the
sensor fusion algorithm. Instead, it is dependent on the amplitude and frequency
of the movement and a major contribution to the error derives from the
orientation of the rotation axis w.r.t. the gravity vector. Absolute and relative
errors upper bounds are found respectively in the range [0.7 degrees / 8.2
degrees ] and [1.0 degrees / 10.3 degrees ]. Alongside dynamic, static accuracy
is thoroughly investigated, also with an emphasis on convergence behavior of the
different algorithms. Reported results emphasize critical issues associated with
the use of this technology and provide a baseline level of performance for the
human motion related application.
PMID- 27612144
TI - Use of Selective Serotonin Reuptake Inhibitors and Risks of Stroke in Patients
with Obsessive Compulsive Disorder: A Population-Based Study.
AB - BACKGROUND: Previous research has suggested a link between antidepressants use
and the development of cerebrovascular events, but there has never been any study
investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients
treated with a selective serotonin reuptake inhibitor (SSRI). METHODS: A
retrospective observational cohort study was conducted using data from the
National Health Insurance Database of Taiwan between the year of 2001 and 2009. A
total of 527 OCD patients with 412 subjects in the SSRI use group and 115 in the
non SSRI use group were included. Multivariable Cox proportional-hazards models
were used to explore the associations between SSRI use and the occurrence of
stroke, controlling for age, gender, concomitant medications, and comorbid
medical illnesses. RESULTS: A total of nineteen OCD patients were diagnosed with
new onset of stroke during the follow-up period including six cases in the SSRI
group and thirteen in the non SSRI use group. SSRI use was demonstrated to be
associated with a decreased risk of stroke (hazard ratio [HR] = 0.30; 95%
confidence interval [CI] = 0.10-0.86, P = 0.02). The increase in age-related risk
of strokes was 2.55 per decade (HR = 2.55; 95% CI = 1.74-3.75, P<0.001).
Alternatively, sex, concomitant use of aspirin and non-steroidal anti
inflammatory drugs, and comorbidities with angina pectoris, diabetes mellitus,
hypertension, and hyperlipidemia were not found to be associated with an
increased risk for stroke in OCD patients. CONCLUSIONS: Our study showed that
SSRI use was associated with decreased risk of stroke in OCD patients. Further
investigation into the possible biological mechanisms underlying the relationship
between stroke and SSRI use in OCD patients is warranted.
PMID- 27612145
TI - Predicting 10-Year Risk of Fatal Cardiovascular Disease in Germany: An Update
Based on the SCORE-Deutschland Risk Charts.
AB - Estimation of absolute risk of cardiovascular disease (CVD), preferably with
population-specific risk charts, has become a cornerstone of CVD primary
prevention. Regular recalibration of risk charts may be necessary due to
decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal
CVD risk assessment were first calibrated for Germany with 1998 risk factor level
data and 1999 mortality statistics. We present an update of these risk charts
based on the SCORE methodology including estimates of relative risks from SCORE,
risk factor levels from the German Health Interview and Examination Survey for
Adults 2008-11 (DEGS1) and official mortality statistics from 2012. Competing
risks methods were applied and estimates were independently validated. Updated
risk charts were calculated based on cholesterol, smoking, systolic blood
pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk
estimates of fatal CVD were lower according to the updated risk charts compared
to the first calibration for Germany. In a nationwide sample of 3062 adults aged
40-65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD
estimated by the updated charts was lower by 29% and the estimated proportion of
high risk people (10-year risk > = 5%) by 50% compared to the older risk charts.
This recalibration shows a need for regular updates of risk charts according to
changes in mortality and risk factor levels in order to sustain the
identification of people with a high CVD risk.
PMID- 27612146
TI - Assessing the Impact of Air Pollution on Grain Yield of Winter Wheat - A Case
Study in the North China Plain.
AB - The major wheat production region of China the North China Plain (NCP) is
seriously affected by air pollution. In this study, yield of winter wheat
(Triticum aestivum L.) was analyzed with respect to the potential impact of air
pollution index under conditions of optimal crop management in the NCP from 2001
to 2012. Results showed that air pollution was especially serious at the early
phase of winter wheat growth significantly influencing various weather factors.
However, no significant correlations were found between final grain yield and the
weather factors during the early growth phase. In contrast, significant
correlations were found between grain yield and total solar radiation gap,
sunshine hour gap, diurnal temperature range and relative humidity during the
late growing phase. To disentangle the confounding effects of various weather
factors, and test the isolated effect of air pollution induced changes in
incoming global solar radiation on yield under ceteris paribus conditions, crop
model based scenario-analysis was conducted. The simulation results of the
calibrated Agricultural Production Systems Simulator (APSIM) model indicated that
a reduction in radiation by 10% might cause a yield reduction by more than 10%.
Increasing incident radiation by 10% would lead to yield increases of (only) 7%,
with the effects being much stronger during the late growing phase compared to
the early growing phase. However, there is evidence that APSIM overestimates the
effect of air pollution induced changes on radiation, as it does not consider the
changes in radiative properties of solar insulation, i.e. the relative increase
of diffuse over direct radiation, which may partly alleviate the negative effects
of reduced total radiation by air pollution. Concluding, the present study could
not detect a significantly negative effect of air pollution on wheat yields in
the NCP.
PMID- 27612147
TI - A Novel Technique to Reconstruct Tricuspid Valve Anterior Leaflet in Massive
Endocarditis.
AB - Tricuspid valve (TV) endocarditis is a common complication in intravenous drug
addicts. In case of TV replacement, the main issue is the high risk of new
endocarditis on TV prosthesis. On November 2014, a 44 year-old male patient with
a history of intravenous drug addiction was referred for TV endocarditis owing to
Staphylococcus aureus and severe regurgitation complicated by pulmonary embolism
and heart failure. Preoperative echocardiography showed a large vegetation of the
anterior leaflet (1.95 * 0.92 cm) covering a huge hole in the leaflet itself.
Herein, a novel technique for the treatment of massive endocarditis of the TV is
described. Complete anterior leaflet reconstruction was achieved with a huge
equine pericardium patch along with native chordae tendinae reimplantation onto
the free edge of the patch. Finally, a ring annuloplasty was performed to
stabilize the valve reconstruction. The postoperative course was uneventful with
evidence of trivial tricuspid regurgitation and no signs of IE recurrence.
Complete reconstruction of the anterior leaflet with a patch of xenopericardium
and native chordae tendinae reimplantation might be an alternative technique to
TV replacement.
PMID- 27612148
TI - Anterior Mitral Leaflet Augmentation for Ischemic Mitral Regurgitation Performed
Via a Right Thoracotomy Approach.
AB - Ischemic mitral regurgitation (MR) after myocardial infarction is associated with
poor long-term survival, and the optimal treatment strategy remains debated. The
most common repair technique used is a restrictive annuloplasty. However, up to
15% to 30% of patients experience recurrent MR owing to progressive left
ventricular remodeling and geometric distortion of the mitral valve apparatus.
Anterior mitral leaflet augmentation using a pericardial patch, in combination
with a true-sized mitral annuloplasty, has been proposed as an adjunctive
technique to increase the durability of valve repair for ischemic MR. Herein, we
describe 2 cases of anterior mitral leaflet augmentation with annuloplasty repair
for severe ischemic MR via a minimally invasive right thoracotomy, and review the
literature regarding patient selection and clinical outcomes of this technique.
PMID- 27612150
TI - Comment on "The importance of determining the limit of detection of non-invasive
prenatal testing methods".
PMID- 27612149
TI - Tumor-Preferential Induction of Immune Responses and Epidermal Cell Death in
Actinic Keratoses by Ingenol Mebutate.
AB - The rapid and strong clinical efficacy of the first-in-class, ingenol mebutate,
against actinic keratosis (AK) has resulted in its recent approval. We conducted
the first comprehensive analysis of the cellular and molecular mode of action of
topical ingenol mebutate 0.05% gel in both AK and uninvolved skin of 26 patients
in a phase I, single-center, open-label, within-patient comparison. As early as 1
day after application, ingenol mebutate induced profound epidermal cell death,
along with a strong infiltrate of CD4+ and CD8+ T-cells, neutrophils, and
macrophages. Endothelial ICAM-1 activation became evident after 2 days. The
reaction pattern was significantly more pronounced in AK compared with uninvolved
skin, suggesting a tumor-preferential mode of action. Extensive molecular
analyses and transcriptomic profiling of mRNAs and microRNAs demonstrated
alterations in gene clusters functionally associated with epidermal development,
inflammation, innate immunity, and response to wounding. Ingenol mebutate reveals
a unique mode of action linking directly to anti-tumoral effects. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01387711.
PMID- 27612151
TI - Response to "The importance of determining the limit of detection of non-invasive
prenatal testing methods".
PMID- 27612152
TI - MicroRNA Gene Expression Signature Driven by miR-9 Overexpression in Ovarian
Clear Cell Carcinoma.
AB - Previous studies have identified microRNA (miRNA) involvement in human cancers.
This study aimed to elucidate potential clinical and biological associations of
ovarian cancer-related miRNA gene expression profiles in high-grade serous
carcinoma (HGSC) and ovarian clear cell carcinoma (OCCC). Accordingly, we
investigated 27 patients with ovarian cancer (12 HGSC and 15 OCCC cases) using
quantitative real-time reverse transcription polymerase chain reaction to
determine the cancer-related miRNA expressions. Gene Cluster 3.0 was used for
hierarchical clustering analysis, and differentially expressed miRNAs between
HGSC and OCCC were identified by the class comparison analysis using BRB
ArrayTools. An unsupervised hierarchical clustering analysis identified two
distinct miRNA expression clusters, with histological subtype-related significant
differences in the associations between clusters and clinicopathological
features. A comparison of miRNA expression in HGSCs and OCCCs identified five
miRNAs (miR-132, miR-9, miR-126, miR-34a, and miR-21), with OCCCs demonstrating a
statistically higher expression. Further investigation of the biological
significance of miR-9 overexpression in OCCC revealed that miR-9 inhibition
reduced the cell invasion ability and upregulated E-cadherin expression. Using a
luciferase reporter assay, we further demonstrated the direct binding of miR-9 to
E-cadherin. Global cancer-related miRNA expression analysis identified
statistically unique profiles that could discriminate ovarian cancer histotypes.
In OCCC, miR-9 overexpression may affect pathogenesis by targeting E-cadherin,
thereby inducing an epithelial-mesenchymal transition. Therefore, miR-9 may be a
promising therapeutic target strategy for OCCC.
PMID- 27612153
TI - Development of a Consistent and Reproducible Porcine Scald Burn Model.
AB - There are very few porcine burn models that replicate scald injuries similar to
those encountered by children. We have developed a robust porcine burn model
capable of creating reproducible scald burns for a wide range of burn conditions.
The study was conducted with juvenile Large White pigs, creating replicates of
burn combinations; 50 degrees C for 1, 2, 5 and 10 minutes and 60 degrees C, 70
degrees C, 80 degrees C and 90 degrees C for 5 seconds. Visual wound examination,
biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7
days post-burn. A consistent water temperature was maintained within the scald
device for long durations (49.8 +/- 0.1 degrees C when set at 50 degrees C). The
macroscopic and histologic appearance was consistent between replicates of burn
conditions. For 50 degrees C water, 10 minute duration burns showed significantly
deeper tissue injury than all shorter durations at 24 hours post-burn (p <=
0.0001), with damage seen to increase until day 3 post-burn. For 5 second
duration burns, by day 7 post-burn the 80 degrees C and 90 degrees C scalds had
damage detected significantly deeper in the tissue than the 70 degrees C scalds
(p <= 0.001). A reliable and safe model of porcine scald burn injury has been
successfully developed. The novel apparatus with continually refreshed water
improves consistency of scald creation for long exposure times. This model allows
the pathophysiology of scald burn wound creation and progression to be examined.
PMID- 27612154
TI - Cypermethrin exposure induces metabolic and stress-related gene expression in
copepodid salmon lice (Lepeophtheirus salmonis).
AB - Cypermethrin has been administered for decades to control salmon lice
(Lepeophtheirus salmonis) infestations in Atlantic salmon farming regions
globally. However, resistance to cypermethrin and other available therapeutants
has threatened the sustainability of this growing industry. To better understand
the effects of cypermethrin on L. salmonis, a 38K oligonucleotide microarray and
RT-qPCR analyses were applied to pools of copepodid larvae exposed to 1.0ppb
cypermethrin or seawater controls for 24h. Phenotypic assessments and global gene
expression profiles showed a significant disruption of homeostasis in copepodid
L. salmonis exposed to cypermethrin. Multiple degradative enzymes were
overexpressed in cypermethrin-treated lice including five trypsin-like serine
proteases and three cytochrome p450s CYP3a24 (p=0.03, fold change (FC)=3.8;
GenBank accession no. JP326960.1), CYP6w1 (p=0.008, FC=5.3; GenBank accession no.
JP317875.1), and CYP6d4 (p=0.01; FC=7.9; GenBank accession no. JP334550.1). These
enzymes represent preliminary markers for understanding the physiological
response of L. salmonis to cypermethrin exposure. A general stress response was
also observed in cypermethrin-treated lice which included differential expression
of cell signaling genes involved in the induction of cell growth, solute
transport, and metabolism. Lastly, a consensus-based analysis was completed with
two previously published L. salmonis transcriptome studies revealing genes that
respond to cypermethrin, emamectin benzoate (another delousing agent) and
hyposalinity. This included concordant differential expression of heat shock beta
1, ammonium transporter Rh types B, and 72kDa type IV collagenase across
different L. salmonis studies. This is currently the most comprehensive
transcriptome assessment of chemical exposure on the first infectious stage of L.
salmonis, providing novel markers for studying drug resistance and general stress
in this important parasite.
PMID- 27612155
TI - Prenatal Effects of Zika Virus and Management of the Pregnant Woman.
AB - The identification of Zika virus as a significant teratogen has raised
international concern, causing the World Health Organization to declare a Public
Health Emergency of International Concern. This has allowed a global mobilization
of experts in tropical infectious diseases, obstetrics, pediatrics, virology,
public health policy, reproductive health, bioethics, and germ cell research to
name just a few. This worldwide crisis has also raised awareness of health care
disparities and concerns regarding the ability of families and societies to
shoulder the long-term financial burden that the follow-up of affected children
will require. There is now strong biologic evidence of causality between Zika
virus and microcephaly and other neurologic abnormalities identified. Multiple
national and international organizations have collaborated to develop guidelines
for the management of pregnant women who reside in or who are exposed to Zika
virus, whether from travel to affected areas or via sexual contact with an
infected individual. These guidelines are updated frequently as data are made
available. Testing algorithms are available and though testing is fraught with
interpretation issues, the development of better diagnostic tests is ongoing.
PMID- 27612156
TI - Pathogenesis and Molecular Mechanisms of Zika Virus.
AB - Zika virus (ZIKV) is one of the most important emerging viruses of 2016. A
developing outbreak in the Americas has demonstrated an association between the
virus and serious clinical manifestations, such as Guillain-Barre syndrome in
adults and congenital malformations in infants born to infected mothers.
Pathogenesis and mechanisms of neurologic or immune disease by ZIKV have not been
clearly delineated. However, several pathways have been described to explain
viral involvement in brain and immune system as well as other organ systems such
as eye, skin, and male and female reproductive tracts. ZIKV activates toll-like
receptor 3 and several pathways have been described to explain the mechanisms at
a molecular level. The mechanism of microcephaly has been more difficult to
demonstrate experimentally, likely due to the multifactorial and complex nature
of the phenotype. This article provides an overview of existing literature on
ZIKV pathogenicity and possible molecular mechanisms of disease as outlined to
date.
PMID- 27612157
TI - Family Planning and Zika Virus: The Power of Prevention.
AB - The connection between infection with the Zika virus (ZKV) and congenital
anomalies such as microcephaly has been generally accepted. Although efforts are
underway to develop preventive interventions such as vaccines, these are not yet
available. Family planning is an effective preventive approach that has been
underemphasized in many lists of research priorities. In addition to acquisition
of ZKV from mosquitoes, sexual transmission from males to females has been
documented. Women at risk of ZKV need access to effective contraception if they
want to avoid or postpone pregnancy, as well as access to safe abortion. There is
often overlap between areas where risk of ZKV acquisition is highest, and areas
where access to reproductive health services may be more limited. Data on the
impact of ZKV on contraceptive use and abortion are sparse, but a few studies
have begun to address these questions. ZKV highlights the need to provide at-risk
women and couples with effective means to prevent or postpone childbearing.
Contraception, prenatal care, and safe abortion should be available to all women.
PMID- 27612159
TI - Exposure of women to trace elements through the skin by direct contact with
underwear clothing.
AB - Heavy metals pose a potential danger to human health when present in textile
materials. In the present study, inductive coupled plasma mass spectrometry
(ICPMS) was used to determine the concentrations and the identity of extractable
inorganic elements from different brands of women undergarments. A total of 120
samples consisting of 63 cottons, 44 nylons and 13 polyesters manufactured in 14
different countries having different colors were analyzed for their extractable
metals contents. Elements analyzed were Ag, Al, As, Ba, Be, Bi, Ca, Cd, Co, Cr,
Cu, Fe, Hg, K, Li, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Ti, V and Zn. Cotton
undergarments were rich in Al, Fe and Zn, nylon undergarments had high levels of
Cr, Cu and Al, while polyester fabrics contained higher levels of Ni and Fe
compared to cotton or nylon. With respect to manufacturing countries, China,
Egypt and India showed the highest concentrations of metals in all fabrics. With
respect to the color, black garments were characteristic by high concentration of
Fe, blue colors with Cu, brown garments with Fe and Cu, green garments with Cu
and Fe, pink garments with Al, purple garments with Al and Cu and red garments
with Cr, Zn and Al. The consumer should be made aware of the potential dangers of
these metals in their clothing.
PMID- 27612158
TI - Zika Virus-Associated Neurological Disease in the Adult: Guillain-Barre Syndrome,
Encephalitis, and Myelitis.
AB - Zika virus (ZIKV) has caused a major infection outbreak in the Americas since
2015. In parallel with the ZIKV epidemic, an increase in cases of neurological
disorders which include Guillain-Barre syndrome (GBS), encephalitis, and myelitis
have been linked to the infection. We reviewed the evidence suggesting a
relationship between ZIKV and neurological disorders in adults. A search of the
literature supporting such link included databases such as PubMed and the World
Health Organization (WHO) surveillance system. Through June 1, 2016, 761
publications were available on PubMed using the search word "Zika." Among those
publications as well as surveillance reports released by the WHO and other health
organizations, 20 articles linked ZIKV with neurological complications other than
microcephaly. They corresponded to population and surveillance studies (n = 7),
case reports (n = 9), case series (n = 3), and case-control studies (n = 1).
Articles were also included if they provided information related to possible
mechanisms of ZIKV neuropathogenesis. Evidence based on epidemiological and
virological information supports the hypothesis that ZIKV infection is associated
with GBS. Although cases of encephalopathy and myelitis have also been linked to
ZIKV infection, the evidence is scarce and there is a need for virological,
epidemiological, and controlled studies to better characterize such relationship.
PMID- 27612160
TI - UiO-66 and its Br-modified derivates for elemental mercury removal.
AB - Phenyl bromine-appended metal-organic frameworks (Br-MOFs) were synthesized and
applied in elemental mercury (Hg0) removal from simulated flue gas, considering
the stability of bromine on the materials at the same time. The techniques of
PXRD, nitrogen adsorption, TGA and XPS were used to characterize the materials.
Phenyl bromide on the MOFs was the main active site for Hg0 capture. The optimal
Br-MOF showed high Hg0 removal efficiency of more than 99% for 48h at 200 degrees
C, whereas the efficiency of un-functionalized MOF and conventional bromine
impregnated active carbon dropped to 59.8% and 91.2% within 5h, respectively. The
crystalline integrity of the Br-MOF was maintained after Hg0 adsorption. Br-MOF
exhibited enhanced Hg0 removal efficiency when SO2 was introduced to the flue
gas. However, exposure Br-MOF to flue gas with steam resulted in low Hg0 removal
efficiency. Bromine leaching experiments proved that Br-MOFs have high bromine
stability over the Hg0 adsorption process, avoiding the possible bromine
pollution caused by the conventional bromine impregnated adsorbents. All of these
results demonstrated the phenyl bromine-appended MOFs to be potential Hg0
adsorbent regarding its high Hg0 capture efficiency and low environmental risk.
PMID- 27612161
TI - Ingestive behavior of supplemented Nellore heifers grazing palisadegrass pastures
managed with different sward heights.
AB - Three sward heights (15, 25 and 35 cm) and three supplement types (energy, energy
protein, and a mineral mix supplement) were evaluated in a 3 * 3 factorial
arrangement distributed in a completely randomized design to study changes in
forage search patterns in Nellore heifers in a continuous grazing system. Pasture
data were collected using two replicates (paddocks) per treatment over four
periods during the rainy season. The behavior assessments were made in the first
and fourth grazing seasons. It was hypothesized that supplements and pasture
management would modify ingestive behavior, considering that animals would
require less time grazing if they had energy requirements met through higher
digestibility of better managed paddocks, or use of supplements high in energy.
Total and green forage masses along with green : dead material ratio were greater
in treatments managed with higher sward heights. Sward managed with 35 cm height
resulted in lower leaf : stem ratio compared with 15 cm sward height treatments.
The animals on the 15 cm pastures spent more time grazing overall and during each
meal, but there were no differences observed in meal numbers in comparison to 35
cm treatments. Heifers fed protein and/or energy supplements spent less time
grazing in the early afternoon, but overall grazing time was the same for all
animals.
PMID- 27612162
TI - Mathematical modeling of the female reproductive system: from oocyte to delivery.
AB - From ovulation to delivery, and through the menstrual cycle, the female
reproductive system undergoes many dynamic changes to provide an optimal
environment for the embryo to implant, and to develop successfully. It is
difficult ethically and practically to observe the system over the timescales
involved in growth and development (often hours to days). Even in carefully
monitored conditions clinicians and biologists can only see snapshots of the
development process. Mathematical models are emerging as a key means to
supplement our knowledge of the reproductive process, and to tease apart
complexity in the reproductive system. These models have been used successfully
to test existing hypotheses regarding the mechanisms of female infertility and
pathological fetal development, and also to provide new experimentally testable
hypotheses regarding the process of development. This new knowledge has allowed
for improvements in assisted reproductive technologies and is moving toward
translation to clinical practice via multiscale assessments of the dynamics of
ovulation, development in pregnancy, and the timing and mechanics of delivery.
WIREs Syst Biol Med 2017, 9:e1353. doi: 10.1002/wsbm.1353 For further resources
related to this article, please visit the WIREs website.
PMID- 27612163
TI - Juvenile porcine temporomandibular joint: Three different cartilaginous
structures?
AB - OBJECTIVE: The temporomandibular joint (TMJ) consists of three cartilaginous
structures: the fossa, disc, and condyle. In juvenile idiopathic arthritis (JIA),
inflammation of the TMJ leads to destruction of the condyle, but not of the fossa
or the disc. Such a different effect of inflammation might be related to
differences in matrix composition of the cartilaginous structures. METHODS: The
matrix composition of the three TMJ structures was analyzed in juvenile porcine
samples and in an in vitro system of cells isolated from each anatomical
structure embedded in 3% agarose gels. RESULTS: The matrix of all three
anatomical structures of the TMJ contained collagen type I and its gene
expression was maintained after isolation. The condyle and the fossa stained
positive for collagen type II and proteoglycans, but the condyle contained
considerably more collagen type II and proteoglycans than the fossa. The disc
contained neither collagen type II protein nor expression of its gene, and the
disc did not stain positive for proteoglycans. Aggrecan gene expression was lower
in the disc compared to condyle and fossa cell-isolates. In general, the cell
isolates in vitro closely mimicked the characteristic features found in the
tissue. CONCLUSION: The collagen type II content of the condyle clearly
distinguished this cartilaginous structure from the disc and fossa. Since
autoimmunity against collagen type II is associated with JIA, the relatively
abundant presence of this type of collagen in the condyle might provide an
explanation why primarily this cartilaginous structure of the TMJ is affected in
JIA patients.
PMID- 27612164
TI - Prenatal diagnosis of Simpson-Golabi-Behmel syndrome.
AB - Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome and it is usually
diagnosed postnatally, on the basis of phenotype. Prenatal ultrasonography may
show fetal alterations, but they are not pathognomonic and most of them are
frequently detectable only from the 20th week of gestation. Nevertheless, early
diagnosis is important to avoid neonatal complications and make timely and
informed decisions about the pregnancy. We report on four fetuses from two
unrelated families, in whom the application of whole exome sequencing and array
CGH allowed the identification of GPC3 alterations causing SGBS. The careful
follow up of pregnancies and more sophisticated analysis of ultrasound findings
led to the identification of early prenatal alterations, which will improve the
antenatal diagnosis of SGBS. (c) 2016 Wiley Periodicals, Inc.
PMID- 27612166
TI - Assessment of fish consumption and mercury exposure among pregnant women in
Jamaica and Trinidad & Tobago.
AB - BACKGROUND: Fish is an essential and traditional element in the diet of most
Caribbean people. However it also contains methylmercury which can have severe
effects on fetal neurodevelopment. The objective of this study was to assess the
fish intake of a selected group of pregnant women from Jamaica and Trinidad &
Tobago and evaluate prenatal mercury exposure, using the placenta as a biomarker.
METHOD: Food frequency questionnaires and placental samples were obtained from
participating parturients at the time of delivery at the University Hospital of
the West Indies in Kingston, Jamaica (N = 100, from November 2012 to March 2013)
and the Mt Hope Women's hospital in St Joseph, Trinidad & Tobago (N = 30, in June
2015). The participants were asked to identify the species of fish and the
frequency of consumption. Placental samples were analysed for mercury using cold
vapour atomic absorption. RESULTS: The fish consumption preferences for pregnant
women, varies based on the marine fish catch production of each country. The main
fish species that contributed to the highest estimated methylmercury exposure in
Jamaica and Trinidad & Tobago were cod and shark, respectively. There was a weak
association between maternal fish intake and placental mercury concentrations.
The mean placental mercury concentrations in Jamaica and Trinidad & Tobago were
0.74 +/- 0.5 MUg/kg and 1.46 +/- 0.6 MUg/kg, wet weight respectively. CONCLUSION:
The results from this study showed an influence of Caribbean fish intake
preferences on mercury exposure and thus a recommendation for continuous bio
monitoring for public health purposes.
PMID- 27612165
TI - Neuroprotective Effects of Sulphated Agaran from Marine Alga Gracilaria cornea in
Rat 6-Hydroxydopamine Parkinson's Disease Model: Behavioural, Neurochemical and
Transcriptional Alterations.
AB - Parkinson's disease (PD) is a multifactorial disease associated with the
degeneration of dopaminergic neurons and behavioural alterations. Natural
bioactive compounds may provide new therapeutic alternatives for
neurodegenerative disorders, such as PD. The sulphated polysaccharides isolated
from marine algae are heterogenic molecules that show different biological
activities. The red marine alga Gracilaria cornea has a sulphated polysaccharide
(SA-Gc) with structure and anti-inflammatory and antinociceptive activities
reported in the literature. Therefore, this study aimed to evaluate the
neuroprotective effects of SA-Gc in rat model PD induced by 6-hydroxydopamine (6
OHDA). Firstly, we established the PD model in rats, induced by an intrastriatal
injection (int.) of 6-OHDA, followed by a single administration of SA-Gc (15, 30
or 60 MUg; int.). On the 14th day, behavioural tests were performed. After
killing, brain areas were dissected and used for neurochemical and/or
transcriptional analyses. The results showed that SA-Gc (60 MUg, int.) promoted
neuroprotective effects in vivo through reducing the oxidative/nitroactive stress
and through alterations in the monoamine contents induced by 6-OHDA. Furthermore,
SA-Gc modulated the transcription of neuroprotective and inflammatory genes, as
well as returning behavioural activities and weight gain to normal conditions.
Thus, this study reports the neuroprotective effects of SA-Gc against 6-OHDA in
rats.
PMID- 27612167
TI - Storytelling as part of cancer rehabilitation to support cancer patients and
their relatives.
AB - Previous research on psychosocial support for cancer-related concerns has
primarily focused on either patients or their relatives, although limited
research is available on how patients and their relatives can be supported
together. The aim of this article is to explore the use of storytelling as a part
of a residential cancer rehabilitation intervention for patients together with
their relatives, with a specific focus on their management of cancer-related
concerns. Ten pairs participated in the intervention and data were generated
through ethnographic fieldwork, including participant observations, informal
conversations and follow-up interviews conducted one month after completing the
intervention. Analysis was performed drawing on narrative theory combined with
social practice theory. The results demonstrate that the use of storytelling and
metaphors intertwined with other course activities, such as dancing and arts &
crafts, provided the patients and their relatives with strategies to manage
cancer-related concerns, which they were later able to apply in their everyday
lives. The study results may be useful to other professionals in clinical
practice for rehabilitation purposes for addressing issues of fear and worry.
PMID- 27612168
TI - Characteristics of bicycle crashes in an adolescent population in Flanders
(Belgium).
AB - INTRODUCTION: In regions where transportation is mainly motorized, air pollution
and traffic congestion are rife. Active transportation such as cycling might be a
solution but safety is a major concern. An efficient science based safety policy
is needed. The aim of this paper is to analyze in depth the bicycle crash causes
and characteristics in an adolescent population (14-18 yr). METHODS: By using
questionnaires for self-reported bicycle crashes, bicycle crash data were
collected from insurance companies (January 2014-June 2015) and from schools
(November 2013-March 2014). Six bicycle crash causes were predefined and possible
differences between schools and insurance companies were analyzed. RESULTS:
Eighty-six school and 78 insurance registered crashes were analyzed. "Distraction
of the cyclist" and "third party crossing a bicycle path failing to see the
cyclist" are the main causes of bicycle crashes (both 29%). Bad (maintained)
infrastructure accounted for 21% of the crash causes. Bicycle crashes reported at
insurance companies needed significantly more medical attention and led to high
absenteeism (57% at least one day of absenteeism). Only 21% of the bicycle
crashes reported at insurance companies were also reported in the official police
database. CONCLUSION: The human factor was the main cause accounting for 79% of
the crashes. Bicycle crashes involving a car accounted for 42% and single bicycle
crashes accounted for 31% of the total number of crashes. From the bicycle
crashes registered at insurance companies 21% was also registered in official
police statistics. A combination of information, education and changing the
bicycle specific environment might reduce the consequences of human errors more
efficiently.
PMID- 27612169
TI - Association between intersection characteristics and perceived crash risk among
school-aged children.
AB - This research examined how environmental attributes near intersections influence
the perceived crash risk among school-aged children, which provides information
on the potential risks of pedestrian crashes that can guide the development of
proactive countermeasures. In a sample of 799 children aged 10-12 years old in
Korea, the environmental attributes of intersections perceived as having a high
risk of producing crashes near elementary schools were investigated using
standard negative binomial and zero-inflated negative binomial models.The results
showed that a higher number of student crossings, a wider road width, the
presence of crosswalks, student-friendly facilities at the intersection, and four
way intersections were significant and positively associated with perceived crash
risk among school-aged children. The findings related to building characteristics
indicated that a higher number of entrances at an intersection increased the
perceived crash risk while higher visibility at the intersection reduced the
perception of risk. Associations with traffic-calming measures were
weak,suggesting that the measures used in the study areas were not effective in
reducing the perceived crash risk. The results of a police-reported crash model
showed that school-aged children have a relatively accurate perception of crash
risk and that the perceived crash risk of school-aged children may provide
valuable information on the intersection characteristics in need of attention
near school sites.
PMID- 27612170
TI - Associations of Rs3744841 and Rs3744843 Polymorphisms in Endothelial Lipase Gene
with Risk of Coronary Artery Disease and Lipid Levels in a Chinese Population.
AB - OBJECTIVE: The aim of the present study was to assess the association between the
2037T/C and 2237G/A polymorphisms in the EL gene and the risk of CAD and lipid
levels in a Chinese population. METHODS: A case-control study including 706
patients with CAD and 315 controls was performed. The polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP) method was used to identify
the genotypes. RESULTS: The EL 2037 T/C polymorphism was associated with CAD risk
and HDL-C levels. No significant differences were found between the EL 2237 G/A
genotypes and CAD risk and lipid levels in the whole population. However,
carriers of the 2237 A allele had higher Apo A1 levels than those with the 2237
GG genotype and in the CAD subgroup (P = 0.044). The CAD cases have a
significantly lower frequency of the C-G haplotypes than the controls, and the T
A haplotype was significantly more common in the CAD patients than in the
controls. CONCLUSIONS: Our study concluded that the EL 2037 T/C polymorphism was
associated with CAD risk and HDL-C levels, and that the C allele might be a
protective factor against CAD in the Chinese Han population. In addition, the EL
2237 A allele might be associated with an increased Apo A1 level in CAD subjects.
PMID- 27612171
TI - The Impact of Diffusion-Weighted MRI on the Definition of Gross Tumor Volume in
Radiotherapy of Non-Small-Cell Lung Cancer.
AB - OBJECTIVE: The study was designed to evaluate diffusion-weighted magnetic
resonance imaging (DWI) vs. PET-CT of the thorax in the determination of gross
tumor volume (GTV) in radiotherapy planning of non-small-cell lung cancer
(NSCLC). MATERIALS AND METHODS: Eligible patients with NSCLC who were supposed to
receive definitive radio(chemo)therapy were prospectively recruited. For MRI, a
respiratory gated T2-weighted sequence in axial orientation and non-gated DWI (b
= 0, 800, 1,400 and apparent diffusion coefficient map [ADC]) were acquired on a
1.5 Tesla scanner. Primary tumors were delineated on FDG-PET/CT (stGTV) and DWI
images (dwGTV). The definition of stGTV was based on the CT and visually adapted
to the FDG-PET component if indicated (e.g., in atelectasis). For DWI, dwGTV was
visually determined and adjusted for anatomical plausibility on T2w sequences.
Beside a statistical comparison of stGTV and dwGTB, spatial agreement was
determined with the "Hausdorff-Distance" (HD) and the "Dice Similarity
Coefficient" (DSC). RESULTS: Fifteen patients (one patient with two synchronous
NSCLC) were evaluated. For 16 primary tumors with UICC stages I (n = 4), II (n =
3), IIIA (n = 2) and IIIB (n = 7) mean values for dwGTV were significantly larger
than those of stGTV (76.6 +/- 84.5 ml vs. 66.6 +/- 75.2 ml, p<0.01). The
correlation of stGTV and dwGTV was highly significant (r = 0.995, p<0.001). Yet,
some considerable volume deviations between these two methods were observed
(median 27.5%, range 0.4-52.1%). An acceptable agreement between dwGTV and stGTV
regarding the spatial extent of primary tumors was found (average HD: 2.25 +/-
0.7 mm; DC 0.68 +/- 0.09). CONCLUSION: The overall level of agreement between PET
CT and MRI based GTV definition is acceptable. Tumor volumes may differ
considerably in single cases. DWI-derived GTVs are significantly, yet modestly,
larger than their PET-CT based counterparts. Prospective studies to assess the
safety and efficacy of DWI-based radiotherapy planning in NSCLC are warranted.
PMID- 27612172
TI - Predicting Breast Tumor Size for Pre-operative Planning: Which Imaging Modality
is Best?
AB - We sought to compare breast tumor size predicted by imaging modality to the
actual pathologic size in order to determine which imaging modality is best at
estimating tumor size. We identified 261 patients with biopsy-proven invasive
ductal (IDC) and/or invasive lobular (ILC) carcinomas with documented tumor
dimensions predicted by imaging and maximum dimensions determined by final
pathology. Results of imaging-predicted dimension were correlated with final
pathological size. Spearman correlations were calculated and compared by Zou's
method and agreement was assessed by McNemar's test. There was no significant
difference (p > 0.05) between correlations of pathologic size by ultrasound (r =
0.71) and magnetic resonance imaging (MRI) (0.76). The correlations between MRI
or ultrasound and pathologic size are significantly stronger than the
correlations between mammography or clinical breast exam and pathologic size (p <
0.05). MRI and ultrasound are both strongly correlated with pathologic size
overall and within grades in both IDC and ILC. The correlations between MRI or
ultrasound and pathologic size are significantly better than the correlations
between mammography or clinical breast exam and pathologic size (p < 0.05).
PMID- 27612174
TI - Human-Wildlife Conflicts in Nepal: Patterns of Human Fatalities and Injuries
Caused by Large Mammals.
AB - Injury and death from wildlife attacks often result in people feeling violent
resentment and hostility against the wildlife involved and, therefore, may
undermine public support for conservation. Although Nepal, with rich
biodiversity, is doing well in its conservation efforts, human-wildlife conflicts
have been a major challenge in recent years. The lack of detailed information on
the spatial and temporal patterns of human-wildlife conflicts at the national
level impedes the development of effective conflict mitigation plans. We examined
patterns of human injury and death caused by large mammals using data from attack
events and their spatiotemporal dimensions collected from a national survey of
data available in Nepal over five years (2010-2014). Data were analyzed using
logistic regression and chi-square or Fisher's exact tests. The results show that
Asiatic elephants and common leopards are most commonly involved in attacks on
people in terms of attack frequency and fatalities. Although one-horned
rhinoceros and bears had a higher frequency of attacks than Bengal tigers, tigers
caused more fatalities than each of these two species. Attacks by elephants
peaked in winter and most frequently occurred outside protected areas in human
settlements. Leopard attacks occurred almost entirely outside protected areas,
and a significantly greater number of attacks occurred in human settlements.
Attacks by one-horned rhinoceros and tigers were higher in the winter, mainly in
forests inside protected areas; similarly, attacks by bears occurred mostly
within protected areas. We found that human settlements are increasingly becoming
conflict hotspots, with burgeoning incidents involving elephants and leopards. We
conclude that species-specific conservation strategies are urgently needed,
particularly for leopards and elephants. The implications of our findings for
minimizing conflicts and conserving these imperiled species are discussed.
PMID- 27612175
TI - GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human
GWAS.
AB - Genome-wide association studies (GWAS) evaluate associations between genetic
variants and a trait or disease of interest free of prior biological hypotheses.
GWAS require stringent correction for multiple testing, with genome-wide
significance typically defined as association p-value <5*10-8. This study
presents a new tool that uses external information about genes to prioritize SNP
associations (GenToS). For a given list of candidate genes, GenToS calculates an
appropriate statistical significance threshold and then searches for trait
associated variants in summary statistics from human GWAS. It thereby allows for
identifying trait-associated genetic variants that do not meet genome-wide
significance. The program additionally tests for enrichment of significant
candidate gene associations in the human GWAS data compared to the number
expected by chance. As proof of principle, this report used external information
from a comprehensive resource of genetically manipulated and systematically
phenotyped mice. Based on selected murine phenotypes for which human GWAS data
for corresponding traits were publicly available, several candidate gene input
lists were derived. Using GenToS for the investigation of candidate genes
underlying murine skeletal phenotypes in data from a large human discovery GWAS
meta-analysis of bone mineral density resulted in the identification of
significantly associated variants in 29 genes. Index variants in 28 of these loci
were subsequently replicated in an independent GWAS replication step,
highlighting that they are true positive associations. One signal, COL11A1, has
not been discovered through GWAS so far and represents a novel human candidate
gene for altered bone mineral density. The number of observed genes that
contained significant SNP associations in human GWAS based on murine candidate
gene input lists was much greater than the number expected by chance across
several complex human traits (enrichment p-value as low as 10-10). GenToS can be
used with any candidate gene list, any GWAS summary file, runs on a desktop
computer and is freely available.
PMID- 27612176
TI - Unravelling the relevance of CLEC12A as a cancer stem cell marker in
myelodysplastic syndrome.
AB - Evidence of distinct disease propagating stem cells in myelodysplastic syndrome
(MDS) has emerged in recent years. However, immunophenotypic characterization of
these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have
previously described aberrant expression of the C-type lectin domain family 12,
member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a
tool for assessing minimal residual disease. Furthermore, CLEC12A has been
proposed as a promising marker of leukaemic stem cells in AML. The role of
CLEC12A in MDS, however, remains to be elucidated. In this study, we found
CLEC12A aberrantly expressed on the CD34+ CD38- cell compartment in 71% (22/31)
of MDS patients, distributed across all Revised International Prognostic Scoring
System risk groups. We showed that the CD34+ CD38- CLEC12A+ cells were indeed
malignant and possessed functional stem cell properties in the long-term colony
initiating cell assay. As opposed to reported findings in AML, we showed that
cancer stem cells from MDS samples derived from both CLEC12A positive and
negative CD34+ CD38- subpopulations. Due to the absence of CLEC12A on normal
haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to
diagnosing and monitoring MDS patients and could furthermore add knowledge about
disease propagating cells in MDS.
PMID- 27612177
TI - Heart failure and risk of dementia: a Danish nationwide population-based cohort
study.
AB - AIMS: The association between heart failure and dementia remains unclear. We
assessed the risk of dementia among patients with heart failure and members of a
general population comparison cohort. METHODS AND RESULTS: Individual-level data
from Danish medical registries were linked in this nationwide population-based
cohort study comparing patients with a first-time hospitalization for heart
failure between 1980 and 2012 and a year of birth-, sex-, and calendar year
matched comparison cohort from the general population. Stratified Cox regression
analysis was used to compute 1-35-year hazard ratios (HRs) for the risk of all
cause dementia and, secondarily, Alzheimer's disease, vascular dementia, and
other dementias. Analyses included 324 418 heart failure patients and 1 622 079
individuals from the general population (median age 77 years, 52% male). Compared
with the general population cohort, risk of all-cause dementia was increased
among heart failure patients [adjusted HR 1.21, 95% confidence interval (CI) 1.18
1.24]. The associations were stronger in men and in heart failure patients under
age 70. Heart failure patients had higher risks of vascular dementia (adjusted HR
1.49, 95% CI 1.40-1.59) and other dementias (adjusted HR 1.30, 95% CI 1.26-1.34)
than members of the general population cohort. Heart failure was not associated
with Alzheimer's disease (adjusted HR 1.00, 95% CI 0.96-1.04). CONCLUSION: Heart
failure was associated with an increased risk of all-cause dementia. Heart
failure may represent a risk factor for dementia, but not necessarily for
Alzheimer's disease.
PMID- 27612179
TI - Letter to Editor: 'Lactate dehydrogenase as a biomarker in oral cancer and oral
submucous fibrosis'.
PMID- 27612180
TI - Investigating nitrate dynamics in a fine-textured soil affected by feedlot
effluents.
AB - Feedlots concentrate large volumes of manure and effluents that contain high
concentrations of nitrate, among other constituents. If not managed properly, pen
surfaces run-off and lagoons overflows may spread those effluents to surrounding
land, infiltrating into the soil. Soil nitrate mobilization and distribution are
of great concern due to its potential migration towards groundwater resources.
This work aimed at evaluating the migration of nitrate originated on feedlots
effluents in a fine-textured soil under field conditions. Soil water constituents
were measured during a three-year period at three distinct locations adjacent to
feedlot retention lagoons representing different degrees of exposure to water
flow and manure accumulation. A simple statistical analysis was undertaken to
identify patterns of observed nitrate and chloride concentrations and electrical
conductivity and their differences with depth. HYDRUS-1D was used to simulate
water flow and solute transport of Cl-, NO4+N, NO3-N and electrical conductivity
to complement field data interpretation. Results indicated that patterns of NO3-N
concentrations were not only notoriously different from electrical conductivity
and Cl- but also ranges and distribution with depth differed among locations. A
combination of dilution, transport, reactions such as
nitrification/denitrification and vegetation water and solute uptake took place
at each plots denoting the complexity of soil-solution behavior under extreme
polluting conditions. Simulations using the concept of single porosity
mobile/immobile water (SP-MIM) managed structural controls and correctly
simulated -all species concentrations under field data constrains. The opposite
was true for the other two locations experiencing near-saturation conditions,
absence of vegetation and frequent manure accumulation and runoff from feedlot
lagoons. Although the results are site specific, findings are relevant to advance
the understanding of NO3-N dynamics resulting from FL operations under heavy
soils.
PMID- 27612178
TI - Effect of a Patient-Centered Communication Intervention on Oncologist-Patient
Communication, Quality of Life, and Health Care Utilization in Advanced Cancer:
The VOICE Randomized Clinical Trial.
AB - Importance: Observational studies demonstrate links between patient-centered
communication, quality of life (QOL), and aggressive treatments in advanced
cancer, yet few randomized clinical trials (RCTs) of communication interventions
have been reported. Objective: To determine whether a combined intervention
involving oncologists, patients with advanced cancer, and caregivers would
promote patient-centered communication, and to estimate intervention effects on
shared understanding, patient-physician relationships, QOL, and aggressive
treatments in the last 30 days of life. Design, Setting, and Participants:
Cluster RCT at community- and hospital-based cancer clinics in Western New York
and Northern California; 38 medical oncologists (mean age 44.6 years; 11 (29%)
female) and 265 community-dwelling adult patients with advanced nonhematologic
cancer participated (mean age, 64.4 years, 146 [55.0%] female, 235 [89%] white;
enrolled August 2012 to June 2014; followed for 3 years); 194 patients had
participating caregivers. Interventions: Oncologists received individualized
communication training using standardized patient instructors while patients
received question prompt lists and individualized communication coaching to
identify issues to address during an upcoming oncologist visit. Both
interventions focused on engaging patients in consultations, responding to
emotions, informing patients about prognosis and treatment choices, and balanced
framing of information. Control participants received no training. Main Outcomes
and Measures: The prespecified primary outcome was a composite measure of patient
centered communication coded from audio recordings of the first oncologist visit
following patient coaching (intervention group) or enrollment (control).
Secondary outcomes included the patient-physician relationship, shared
understanding of prognosis, QOL, and aggressive treatments and hospice use in the
last 30 days of life. Results: Data from 38 oncologists (19 randomized to
intervention) and 265 patients (130 intervention) were analyzed. In fully
adjusted models, the intervention resulted in clinically and statistically
significant improvements in the primary physician-patient communication end point
(adjusted intervention effect, 0.34; 95% CI, 0.06-0.62; P = .02). Differences in
secondary outcomes were not statistically significant. Conclusions and Relevance:
A combined intervention that included oncologist communication training and
coaching for patients with advanced cancer was effective in improving patient
centered communication but did not affect secondary outcomes. Trial Registration:
clinicaltrials.gov Identifier: NCT01485627.
PMID- 27612181
TI - Eliciting Preferences of Multimorbid Elderly Adults in Family Practice Using an
Outcome Prioritization Tool.
AB - OBJECTIVES: To explore an outcome prioritization tool (OPT) in eliciting
individuals' preferred health outcomes (remaining alive, maintaining
independence, reducing pain, reducing other symptoms) in the context of
medication review in family practice. DESIGN: Cross-sectional pilot study with
mixed-methods design. SETTING: Family practice. PARTICIPANTS: Multimorbid
individuals (N = 60; aged >=69) with polypharmacy (>=5 chronic medications)
derived from the practice lists of a purposive sample of 13 family physicians
(FPs). MEASUREMENTS: Participants were asked to prioritize each health outcome
according the trade-off principle, and FPs used this prioritization for
medication review. The acceptability and practicality were measured using a
questionnaire for FPs and participants and semistructured interviews with FPs.
RESULTS: Ninety-two percent of participants found the OPT understandable, and 55%
could easily prioritize between health outcomes. Working with the OPT (mean
duration 31 minutes) was a new approach for FPs, but they became more adept at
using it. For FPs, the OPT provides better understanding of their patients.
Participants and FPs thought that there should be a specific reason to discuss
preferences, such as (expected) decline in health status. CONCLUSION: The OPT
appears to be promising in eliciting patient preferences but is not suitable for
routine medication review at present. Further optimization before actual use is
needed (e.g., knowledge in which clinical situations the OPT is useful). More
information is needed on how individuals and their families perceive the tool.
PMID- 27612182
TI - The zebrafish eye-a paradigm for investigating human ocular genetics.
AB - Although human epidemiological and genetic studies are essential to elucidate the
aetiology of normal and aberrant ocular development, animal models have provided
us with an understanding of the pathogenesis of multiple developmental ocular
malformations. Zebrafish eye development displays in depth molecular complexity
and stringent spatiotemporal regulation that incorporates developmental
contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar
to that seen in humans. For this reason, and due to its genetic tractability,
external fertilisation, and early optical clarity, the zebrafish has become an
invaluable vertebrate system to investigate human ocular development and disease.
Recently, zebrafish have been at the leading edge of preclinical therapy
development, with their amenability to genetic manipulation facilitating the
generation of robust ocular disease models required for large-scale genetic and
drug screening programmes. This review presents an overview of human and
zebrafish ocular development, genetic methodologies employed for zebrafish
mutagenesis, relevant models of ocular disease, and finally therapeutic
approaches, which may have translational leads in the future.
PMID- 27612184
TI - Ranibizumab for the treatment of wet AMD: a summary of real-world studies.
PMID- 27612183
TI - Design and performance of a large lumen glaucoma drainage device.
AB - PurposeWe report the in vivo testing of a large-lumen glaucoma drainage (LL-GDD)
device equipped with a flow regulator. The device's membrane can be non
invasively opened with laser in the postoperative period to adjust aqueous flow
and intraocular pressure.MethodsThe initial LL-GDD prototypes were constructed
using 22 G silicone angiocatheters cut down to size. A 10 nm PVDF membrane was
then affixed to the end using cyanoacrylate. The LL-GDD was tested first in a
model eye equipped with ports for infusion and pressure measurement and in New
Zealand rabbits.ResultsNew Zealand white satin cross rabbits were used, two eyes
receiving the LL-GDD and the two fellow eyes serving as the control group with no
intervention performed. After the procedure, the IOP in the LL-GGD surgical group
dropped an average of 5.5 mm Hg (P=0.001), which was maintained until the
membrane laser procedure at week 5 resulting in an average IOP reduction of 1.8
mm Hg. At week 7, the average IOP in the surgical group was 11 mm Hg compared
with 18 mm Hg in the control group (P<0.001). A second laser procedure was done
to completely open the membrane face, which resulted in an immediate drop in the
average IOP of the surgical group by another 2.7 mm Hg, which was maintained
until the study termination at day 55.ConclusionsThe large-lumen glaucoma
drainage device demonstrated an ability both to prevent immediate postoperative
hypotony and to allow progressively lower IOP on demand in this proof-of-concept
study.
PMID- 27612185
TI - A novel mutation in A4GALT was identified in a Chinese individual with p
phenotype.
PMID- 27612186
TI - Loss-of-function mutation in RUSC2 causes intellectual disability and secondary
microcephaly.
AB - Inherited aberrancies in intracellular vesicular transport are associated with a
variety of neurological and non-neurological diseases. RUSC2 is a gene found on
chromosome 9p13.3 that codes for iporin, a ubiquitous protein with high
expression in the brain that interacts with Rab proteins (GTPases implicated in
intracellular protein trafficking). Although mutations in Rab proteins have been
described as causing brain abnormalities and intellectual disability, until now
no disease-causing mutations in RUSC2 have ever been reported in humans. We
describe, to our knowledge for the first time, three patients with inherited
homozygous nonsense mutations identified in RUSC2 on whole-exome sequencing. All
three patients had central hypotonia, microcephaly, and moderate to severe
intellectual disability. Two patients had additional features of early-onset
epilepsy and absence of the splenium. This report adds to the ever-expanding
landscape of genetic causes of intellectual disability and increases our
understanding of the cellular processes underlying this important neurological
entity.
PMID- 27612187
TI - Maternal protein restriction induced-hypertension is associated to oxidative
disruption at transcriptional and functional levels in the medulla oblongata.
AB - Maternal protein restriction during pregnancy and lactation predisposes the adult
offspring to sympathetic overactivity and arterial hypertension. Although the
underlying mechanisms are poorly understood, dysregulation of the oxidative
balance has been proposed as a putative trigger of neural-induced hypertension.
The aim of the study was to evaluate the association between the oxidative status
at transcriptional and functional levels in the medulla oblongata and maternal
protein restriction induced-hypertension. Wistar rat dams were fed a control
(normal protein; 17% protein) or a low protein ((Lp); 8% protein) diet during
pregnancy and lactation, and male offspring was studied at 90 days of age. Direct
measurements of baseline arterial blood pressure (ABP) and heart rate (HR) were
recorded in awakened offspring. In addition, quantitative RT-PCR was used to
assess the mRNA expression of superoxide dismutase 1 (SOD1) and 2 (SOD2),
catalase (CAT), glutathione peroxidase (GPx), Glutamatergic receptors (Grin1,
Gria1 and Grm1) and GABA(A)-receptor-associated protein like 1 (Gabarapl1).
Malondialdehyde (MDA) levels, CAT and SOD activities were examined in ventral and
dorsal medulla. Lp rats exhibited higher ABP. The mRNA expression levels of SOD2,
GPx and Gabarapl1 were down regulated in medullary tissue of Lp rats (P<.05, t
test). In addition, we observed that higher MDA levels were associated to
decreased SOD (approximately 45%) and CAT (approximately 50%) activities in
ventral medulla. Taken together, our data suggest that maternal protein
restriction induced-hypertension is associated with medullary oxidative
dysfunction at transcriptional level and with impaired antioxidant capacity in
the ventral medulla.
PMID- 27612188
TI - Phospholipase Cepsilon Modulates Rap1 Activity and the Endothelial Barrier.
AB - The phosphoinositide-specific phospholipase C, PLCepsilon, is a unique signaling
protein with known roles in regulating cardiac myocyte growth, astrocyte
inflammatory signaling, and tumor formation. PLCepsilon is also expressed in
endothelial cells, however its role in endothelial regulation is not fully
established. We show that endothelial cells of multiple origins, including human
pulmonary artery (HPAEC), human umbilical vein (HUVEC), and immortalized brain
microvascular (hCMEC/D3) endothelial cells, express PLCepsilon. Knockdown of
PLCepsilon in arterial endothelial monolayers decreased the effectiveness of the
endothelial barrier. Concomitantly, RhoA activity and stress fiber formation were
increased. PLCepsilon-deficient arterial endothelial cells also exhibited
decreased Rap1-GTP levels, which could be restored by activation of the Rap1 GEF,
Epac, to rescue the increase in monolayer leak. Reintroduction of PLCepsilon
rescued monolayer leak with both the CDC25 GEF domain and the lipase domain of
PLCepsilon required to fully activate Rap1 and to rescue endothelial barrier
function. Finally, we demonstrate that the barrier promoting effects PLCepsilon
are dependent on Rap1 signaling through the Rap1 effector, KRIT1, which we have
previously shown is vital for maintaining endothelial barrier stability. Thus we
have described a novel role for PLCepsilon PIP2 hydrolytic and Rap GEF activities
in arterial endothelial cells, where PLCepsilon-dependent activation of
Rap1/KRIT1 signaling promotes endothelial barrier stability.
PMID- 27612190
TI - Study of the antioxidant activity of Thymus sibthorpii Bentham (Lamiaceae).
AB - From the aerial parts of Thymus sibthorpii Bentham (Lamiaceae), five flavonoids
apigenin (1), 7-methoxy-apigenin (2), naringenin (3), eriodictyol (4) and
eriodictyol-7-glucoside (5), have been isolated together with caffeic acid methyl
ester (6), rosmarinic acid (7) and rosmarinic acid methyl ester (8). The
structures of the isolated compounds were established by spectroscopic methods.
The extracts and the isolated compounds were tested for their free radical
scavenging activity using the following in vitro assays: (i) interaction with the
free stable radical of DPPH (1,1-diphenyl-2-picrylhydrazyl), (ii) inhibition of
linoleic acid lipid peroxidation induced by the dihydrochloric acid of 2,2-azobis
2-amidinepropane (AAPH) and (iii) the scavenging activity of enzymatically
produced superoxide anion. Their inhibitory activity toward soybean lipoxygenase
was evaluated in vitro, using linoleic acid as a substrate. The antioxidant
results of the extracts are discussed in terms of their constitution in phenolic
compounds, which were determined following the Folin-Ciocalteu method.
PMID- 27612189
TI - PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte
Hypertrophy and Cardiac Fibrosis.
AB - Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy
type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal
cardiac arrhythmia are observed in patients with CGL4 who have homozygous
PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and
caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in
the heart causes cardiac hypertrophy with loss of caveolae. However, it remains
unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here,
we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF-/-) mice.
Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF
/- mice. PTRF-/- mice at 16 weeks of age developed a progressive cardiomyopathic
phenotype with wall thickening of left ventricles and reduced fractional
shortening evaluated by echocardiography. Electrocardiography revealed that PTRF
/- mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads.
Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive
interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was
also induced in PTRF-/- hearts. Western blotting analysis and quantitative RT-PCR
revealed that Cav3 expression was suppressed in PTRF-/- hearts compared with that
in wild-type (WT) ones. ERK1/2 was activated in PTRF-/- hearts compared with that
in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is
sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and
cardiomyopathy, which is partly attributable to Cav3 reduction in the heart.
PMID- 27612191
TI - Temperature-sensitive gating of TRPV1 channel as probed by atomistic simulations
of its trans- and juxtamembrane domains.
AB - Heat-activated transient receptor potential channel TRPV1 is one of the most
studied eukaryotic proteins involved in temperature sensation. Upon heating, it
exhibits rapid reversible pore gating, which depolarizes neurons and generates
action potentials. Underlying molecular details of such effects in the pore
region of TRPV1 is of a crucial importance to control temperature responses of
the organism. Despite the spatial structure of the channel in both open (O) and
closed (C) states is known, microscopic nature of channel gating and mechanism of
thermal sensitivity are still poorly understood. In this work, we used
unrestrained atomistic molecular dynamics simulations of TRPV1 (without N- and C
terminal cytoplasmic domains) embedded into explicit lipid bilayer in its O- and
C-states. We found that the pore domain with its neighboring loops undergoes
large temperature-dependent conformational transitions in an asymmetric way, when
fragments of only one monomer move with large amplitude, freeing the pore upon
heating. Such an asymmetrical gating looks rather biologically relevant because
it is faster and more reliable than traditionally proposed "iris-like" symmetric
scheme of channel opening. Analysis of structural, dynamic, and hydrophobic
organization of the pore domain revealed entropy growth upon TRPV1 gating, which
is in line with current concepts of thermal sensitivity.
PMID- 27612192
TI - Association Between Endocrine Diseases and Serous Otitis Media in Children.
AB - OBJECTIVE: Otitis media with effusion (OME) is a condition in which fluid is
retained in the middle ear cavity. The association between endocrine disorders
and OME has not yet been determined. This study aimed to investigate the presence
of OME in children diagnosed with an endocrine disease and the relationship
between these two conditions. METHODS: The study was conducted on 918 pediatric
patients (440 boys, 478 girls; mean age: 8.40, range 3-15 years) and 158 healthy
controls (76 boys, 79 girls; mean age: 8.31, range 3-15 years). All children
underwent an ear examination and a tympanometry performed by an
otorhinolaryngologist. Tympanometry results were used to diagnose OME. RESULTS:
OME was detected in 205 (22.3%) of 918 patients and in 19 (12.0%) of 158 subjects
in the control group. The difference in frequency of OME between the two groups
was statistically significant (p=0.003). CONCLUSION: The results of the study
reveal that there may be a tendency towards the occurrence of OME in pediatric
endocrinology patients.
PMID- 27612193
TI - Prodigiosin - A Multifaceted Escherichia coli Antimicrobial Agent.
AB - Despite a considerable interest in prodigiosin, the mechanism of its
antibacterial activity is still poorly understood. In this work, Escherichia coli
cells were treated with prodigiosin to determine its antimicrobial effect on
bacterial physiology. The effect of prodigiosin was concentration dependent. In
prodigiosin treated cells above MIC value no significant DNA damage or
cytoplasmic membrane disintegration was observed. The outer membrane, however,
becomes leaky. Cells had severely decreased respiration activity. In prodigiosin
treated cells protein and RNA synthesis were inhibited, cells were elongated but
could not divide. Pre-treatment with prodigiosin improved E. coli survival rate
in media containing ampicillin, kanamycin and erythromycin but not phleomycin.
The results suggest that prodigiosin acts as a bacteriostatic agent in E. coli
cells. If prodigiosin was diluted, cells resumed growth. The results indicate
that prodigiosin has distinct mode of antibacterial action in different bacteria.
PMID- 27612194
TI - A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular
Monoamine Transporter Type 2.
AB - In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to
be a useful positron emission tomography (PET) imaging agent for various
neurodegenerative disorders. Here, we described the radiosynthesis and evaluation
of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine
transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)
11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the
presence of 5 M NaOH. It had a slightly better average radiochemical yield of
35.3 +/- 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ
(30.5 +/- 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to
cerebellum ratio of 3.74 +/- 0.21 at 40 min post-injection, while the ratio of 9
(+)-11C-DTBZ was 2.50 +/- 0.33. This indicated that 10-(+)-11C-DTBZ has a higher
specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a
potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ
to include dynamic brain distribution in rat brains.
PMID- 27612196
TI - Diving deep into hyperbaric oxygen therapy.
PMID- 27612197
TI - Evidence-based safe practice guidelines for I.V. push medications.
PMID- 27612195
TI - Mechanisms, prediction, and prevention of ACL injuries: Cut risk with three
sharpened and validated tools.
AB - Economic and societal pressures influence modern medical practice to develop and
implement prevention strategies. Anterior cruciate ligament (ACL) injury
devastates the knee joint leading to short term disability and long term
sequelae. Due to the high risk of long term osteoarthritis in all treatment
populations following ACL injury, prevention is the only effective intervention
for this life-altering disruption in knee health. The "Sequence of Prevention"
Model provides a framework to monitor progress towards the ultimate goal of
preventing ACL injuries. Utilizing this model, our multidisciplinary
collaborative research team has spent the last decade working to delineate injury
mechanisms, identify injury risk factors, predict which athletes are at-risk for
injury, and develop ACL injury prevention programs. Within this model of injury
prevention, modifiable factors (biomechanical and neuromuscular) related to
injury mechanisms likely provide the best opportunity for intervention strategies
aimed to decrease the risk of ACL injury, particularly in female athletes.
Knowledge advancements have led to the development of potential solutions that
allow athletes to compete with lowered risk of ACL injury. Design and integration
of personalized clinical assessment tools and targeted prevention strategies for
athletes at high risk for ACL injury may transform current prevention practices
and ultimately significantly reduce ACL injury incidence. This 2016 OREF Clinical
Research Award focuses on the authors' work and contributions to the field. The
author's acknowledge the many research groups who have contributed to the current
state of knowledge in the fields of ACL injury mechanisms, injury risk screening
and injury prevention strategies. (c) 2016 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 34:1843-1855, 2016.
PMID- 27612199
TI - Production of Autoantibodies in Chronic Hepatitis B Virus Infection Is Associated
with the Augmented Function of Blood CXCR5+CD4+ T Cells.
AB - T follicular helper cells (Tfh) provide help to B cells to support their
activation, expansion and differentiation. However, the role of Tfh cells in
chronic HBV infection is poorly defined. The aim of this research was to examine
the function of Tfh cells and whether they are involved in HBV related disease.
Blood CXCR5+CD4+T cells and B cells in 85 patients with chronic HBV infection
(HBV patients) and health controls (HC) were examined by flow cytometry. The
molecule expression in blood CXCR5+CD4+ T cells was detected by real-time PCR.
Blood CXCR5+CD4+ T cells and B cells were co-cultured and the production of Ig
and cytokines was detected by ELISA. Autoantibodies were detected by indirect
immunofluorescence and immunospot assay. We found that blood CXCR5+CD4+ T cells
in patients with chronic HBV infection (HBV patients) expressed higher level of
activation related molecules and cytokines than that from health controls (HC).In
HBV patients, the frequency of blood CXCR5+CD4+ T cells was significantly
correlated with serum ALT and AST. We also found that blood CXCR5+CD4+ T cells
from HBV patients could induce B cells to secret higher level of immunoglobulin
than that from HC. Several autoantibodies, including ANA, ss-A, ss-B, Scl-70, Jo
1, ect, were indeed positive in 65% HBV patients. Among HBV patients, expression
of function related molecules was significantly higher in blood CXCR5+CD4+ T
cells from patients with autoantibodies than that without autoantibodies. Our
research indicated that blood CXCR5+CD4+ T cells from HBV patients were over
activated and show augmented capacity to help B cells for antibody secreting,
which might correlated with liver inflammation and the production of
autoantibodies in extrahepatic manifestations.
PMID- 27612198
TI - Early Diagnosis of Respiratory Abnormalities in Asbestos-Exposed Workers by the
Forced Oscillation Technique.
AB - BACKGROUND: The current reference test for the detection of respiratory
abnormalities in asbestos-exposed workers is spirometry. However, spirometry has
several shortcomings that greatly affect the efficacy of current asbestos control
programs. The forced oscillation technique (FOT) represents the current state-of
the-art technique in the assessment of lung function. This method provides a
detailed analysis of respiratory resistance and reactance at different
oscillatory frequencies during tidal breathing. Here, we evaluate the FOT as an
alternative method to standard spirometry for the early detection and
quantification of respiratory abnormalities in asbestos-exposed workers.
METHODOLOGY/PRINCIPAL FINDINGS: Seventy-two subjects were analyzed. The control
group was composed of 33 subjects with a normal spirometric exam who had no
history of smoking or pulmonary disease. Thirty-nine subjects exposed to asbestos
were also studied, including 32 volunteers in radiological category 0/0 and 7
volunteers with radiological categories of 0/1 or 1/1. FOT data were interpreted
using classical parameters as well as integer (InOr) and fractional-order (FrOr)
modeling. The diagnostic accuracy was evaluated by investigating the area under
the receiver operating characteristic curve (AUC). Exposed workers presented
increased obstruction (resistance p<0.001) and a reduced compliance (p<0.001),
with a predominance of obstructive changes. The FOT parameter changes were
correlated with the standard pulmonary function analysis methods (R = -0.52,
p<0.001). Early respiratory abnormalities were identified with a high diagnostic
accuracy (AUC = 0.987) using parameters obtained from the FrOr modeling. This
accuracy was significantly better than those obtained with classical (p<0.001)
and InOr (p<0.001) model parameters. CONCLUSIONS: The FOT improved our knowledge
about the biomechanical abnormalities in workers exposed to asbestos.
Additionally, a high diagnostic accuracy in the diagnosis of early respiratory
abnormalities in asbestos-exposed workers was obtained. This makes the FOT
particularly useful as a screening tool in the context of asbestos control and
elimination. Moreover, it can facilitate epidemiological research and the
longitudinal follow-up of asbestos exposure and asbestos-related diseases.
PMID- 27612201
TI - Glutaminolysis Was Induced by TGF-beta1 through PP2Ac Regulated Raf-MEK-ERK
Signaling in Endothelial Cells.
AB - Vascular endothelial cells can survive under hypoxic and inflammatory conditions
by alterations of the cellular energy metabolism. In addition to high rates of
glycolysis, glutaminolysis is another important way of providing the required
energy to support cellular sprouting in such situations. However, the exact
mechanism in which endothelial cells upregulate glutaminolysis remains unclear.
Here we demonstrated that protein phosphatase 2A (PP2A)-mediated Raf-MEK-ERK
signaling was involved in glutaminolysis in endothelial cells. Using models of
human umbilical vein endothelial cells (HUVECs) treated with transforming growth
factor-beta1 (TGF-beta1), we observed a dramatic induction in cellular glutamate
levels accompanied by Raf-MEK-ERK activation. By addition of U0126, the specific
inhibitor of MEK1/2, the expression of kidney-type glutaminase (KGA, a critical
glutaminase in glutaminolysis) was significantly decreased. Moreover, inhibition
of PP2A by okadaic acid (OA), a specific inhibitor of PP2A phosphatase activity
or by depletion of its catalytic subunit (PP2Ac), led to a significant
inactivation of Raf-MEK-ERK signaling and reduced glutaminolysis in endothelial
cells. Taken together, these results indicated that PP2A-dependent Raf-MEK-ERK
activation was involved in glutaminolysis and inhibition of PP2A signals was
sufficient to block Raf-MEK-ERK pathway and reduced glutamine metabolism in
endothelial cells.
PMID- 27612202
TI - Decreased beta-Cell Function Is Associated with Reduced Skeletal Muscle Mass in
Japanese Subjects without Diabetes.
AB - BACKGROUND: Decreased insulin secretion has a great impact on the incidence of
type 2 diabetes in Japanese subjects. It is not clear whether beta-cell function
is related to muscle mass in subjects without diabetes. We investigated the
relationship between beta-cell function and skeletal muscle mass in Japanese
subjects without diabetes. METHODS: The study included 1098 subjects (538 men and
560 women) aged 40 to 79 years, without diabetes (fasting glucose lower than 126
mg/dL and glycosylated hemoglobin lower than 6.5%), who consulted Osaka Medical
College Health Science Clinic for a medical examination. Appendicular muscle mass
was measured by bioelectrical impedance analysis. Appendicular muscle mass index
was calculated as appendicular muscle mass divided by height squared (kg/m2). The
homeostatic model assessment of beta-cell function was used to assess beta-cell
function. The homeostatic model assessment of insulin resistance was used as a
measure of insulin resistance. The association between appendicular muscle mass
index and clinical parameters of beta-cell function and insulin resistance was
examined. RESULTS: Log-transformed homeostatic model assessment of beta-cell
function and Log-transformed homeostatic model assessment of insulin resistance
showed a normal distribution. In both men and women, there was a significant
positive correlation between appendicular muscle mass index and clinical
parameters of beta-cell function and insulin resistance. Tertile analysis,
following stratification according to appendicular muscle mass index, found that
low appendicular muscle mass index was significantly associated with the Log
homeostatic model assessment of beta-cell function and Log-transformed
homeostatic model assessment of insulin resistance. CONCLUSION: This study shows
that decreased beta cell function is associated with reduced skeletal muscle mass
in Japanese subjects without diabetes.
PMID- 27612200
TI - Increased Obesity-Associated Circulating Levels of the Extracellular Matrix
Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon
Cancer.
AB - BACKGROUND: Excess adipose tissue represents a major risk factor for the
development of colon cancer with inflammation and extracellular matrix (ECM)
remodeling being proposed as plausible mechanisms. The aim of this study was to
investigate whether obesity can influence circulating levels of inflammation
related extracellular matrix proteins in patients with colon cancer (CC),
promoting a microenvironment favorable for tumor growth. METHODS: Serum samples
obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the
study. Enrolled subjects were further subclassified according to the established
diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric
measurements as well as circulating metabolites and hormones were determined.
Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3
like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined
by ELISA. RESULTS: Significant differences in circulating OPN, YKL-40 and TNC
concentrations between the experimental groups were observed, being significantly
increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were
affected by obesity (P<0.05), but no differences were detected regarding the
presence or not of CC. A positive association (P<0.05) with different
inflammatory markers was also detected. CONCLUSIONS: To our knowledge, we herein
show for the first time that obese patients with CC exhibit increased circulating
levels of OPN, YKL-40 and TNC providing further evidence for the influence of
obesity on CC development via ECM proteins, representing promising diagnostic
biomarkers or target molecules for therapeutics.
PMID- 27612204
TI - Probabilistic, Multivariable Flood Loss Modeling on the Mesoscale with BT-FLEMO.
AB - Flood loss modeling is an important component for risk analyses and decision
support in flood risk management. Commonly, flood loss models describe complex
damaging processes by simple, deterministic approaches like depth-damage
functions and are associated with large uncertainty. To improve flood loss
estimation and to provide quantitative information about the uncertainty
associated with loss modeling, a probabilistic, multivariable Bagging decision
Tree Flood Loss Estimation MOdel (BT-FLEMO) for residential buildings was
developed. The application of BT-FLEMO provides a probability distribution of
estimated losses to residential buildings per municipality. BT-FLEMO was applied
and validated at the mesoscale in 19 municipalities that were affected during the
2002 flood by the River Mulde in Saxony, Germany. Validation was undertaken on
the one hand via a comparison with six deterministic loss models, including both
depth-damage functions and multivariable models. On the other hand, the results
were compared with official loss data. BT-FLEMO outperforms deterministic,
univariable, and multivariable models with regard to model accuracy, although the
prediction uncertainty remains high. An important advantage of BT-FLEMO is the
quantification of prediction uncertainty. The probability distribution of loss
estimates by BT-FLEMO well represents the variation range of loss estimates of
the other models in the case study.
PMID- 27612203
TI - The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine
Cytidine Kinase 2.
AB - Fluorocyclopentenylcytosine (RX-3117) is an orally available cytidine analog,
currently in Phase I clinical trial. RX-3117 has promising antitumor activity in
various human tumor xenografts including gemcitabine resistant tumors. RX-3117 is
activated by uridine-cytidine kinase (UCK). Since UCK exists in two forms, UCK1
and UCK2, we investigated which form is responsible for RX-3117 phosphorylation.
For that purpose we transfected A549 and SW1573 cell lines with UCK-siRNAs.
Transfection of UCK1-siRNA efficiently downregulated UCK1-mRNA, but not UCK2-mRNA
expression, and did not affect sensitivity to RX-3117. However, transfection of
UCK2-siRNA completely downregulated UCK2-mRNA and protein and protected both A549
and SW1573 against RX-3117. UCK enzyme activity in two panels of tumor cell lines
and xenograft cells correlated only with UCK2-mRNA expression (r = 0.803 and
0.915, respectively), but not with UCK1-mRNA. Moreover, accumulation of RX-3117
nucleotides correlated with UCK2 expression. In conclusion, RX-3117 is activated
by UCK2 which may be used to select patients potentially sensitive to RX-3117.
PMID- 27612205
TI - PYK10 myrosinase reveals a functional coordination between endoplasmic reticulum
bodies and glucosinolates in Arabidopsis thaliana.
AB - The endoplasmic reticulum body (ER body) is an organelle derived from the ER that
occurs in only three families of the order Brassicales and is suggested to be
involved in plant defense. ER bodies in Arabidopsis thaliana contain large
amounts of beta-glucosidases, but the physiological functions of ER bodies and
these enzymes remain largely unclear. Here we show that PYK10, the most abundant
beta-glucosidase in A. thaliana root ER bodies, hydrolyzes indole glucosinolates
(IGs) in addition to the previously reported in vitro substrate scopolin. We
found a striking co-expression between ER body-related genes (including PYK10),
glucosinolate biosynthetic genes and the genes for so-called specifier proteins
affecting the terminal products of myrosinase-mediated glucosinolate metabolism,
indicating that these systems have been integrated into a common transcriptional
network. Consistent with this, comparative metabolite profiling utilizing a
number of A. thaliana relatives within Brassicaceae identified a clear
phylogenetic co-occurrence between ER bodies and IGs, but not between ER bodies
and scopolin. Collectively, our findings suggest a functional link between ER
bodies and glucosinolate metabolism in planta. In addition, in silico three
dimensional modeling, combined with phylogenomic analysis, suggests that PYK10
represents a clade of 16 myrosinases that arose independently from the other well
documented class of six thioglucoside glucohydrolases. These findings provide
deeper insights into how glucosinolates are metabolized in cruciferous plants and
reveal variation of the myrosinase-glucosinolate system within individual plants.
PMID- 27612206
TI - Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle
cerebral artery occlusion, a model of stroke.
AB - In addition to brain injury stroke patients often suffer gastrointestinal
complications. Neuroimmune interactions involving galectin-3, released from
microglia in the brain, mediates the post-stroke pro-inflammatory response. We
investigated possible consequences of stroke on the enteric nervous system and
the involvement of galectin-3. We show that permanent middle cerebral artery
occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin
3(+/+), but not in galectin-3(-/-), mice. In vitro we show that serum from
galectin-3(+/+), but not from galectin-3(-/-), mice subjected to pMCAO, caused
loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4(-/
) mice were unaffected. Further purified galectin-3 (10(-6) M) caused loss of
cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor
beta-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both
the purified galectin-3 and the galectin-3(+/+) pMCAO serum-induced loss in
vitro. Combined we show that stroke (pMCAO) triggers central and peripheral
galectin-3 release causing enteric neuronal loss through a TLR4 mediated
mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment
of post-stroke complications.
PMID- 27612207
TI - Exchange factors directly activated by cAMP mediate melanocortin 4 receptor
induced gene expression.
AB - Gs protein-coupled receptors regulate many vital body functions by activation of
cAMP response elements (CRE) via cAMP-dependent kinase A (PKA)-mediated
phosphorylation of the CRE binding protein (CREB). Melanocortin 4 receptors
(MC4R) are prototypical Gs-coupled receptors that orchestrate the hypothalamic
control of food-intake and metabolism. Remarkably, the significance of PKA for
MC4R-induced CRE-dependent transcription in hypothalamic cells has not been
rigorously interrogated yet. In two hypothalamic cell lines, we observed that
blocking PKA activity had only weak or no effects on reporter gene expression. In
contrast, inhibitors of exchange factors directly activated by cAMP-1/2 (EPAC
1/2) mitigated MC4R-induced CRE reporter activation and mRNA induction of the
CREB-dependent genes c-fos and thyrotropin-releasing hormone. Furthermore, we
provide first evidence that extracellular-regulated kinases-1/2 (ERK-1/2)
activated by EPACs and not PKA are the elusive CREB kinases responsible for MC4R
induced CREB/CRE activation in hypothalamic cells. Overall, these data emphasize
the pivotal role of EPACs rather than PKA in hypothalamic gene expression
elicited by a prototypical Gs-coupled receptor.
PMID- 27612208
TI - Biologic activity of cyclic and caged phosphates: a review.
AB - The recognition in the early 1960s by Morifusa Eto that tri-o-cresyl phosphate
(TOCP) is hydroxylated by the cytochrome P450 system to an intermediate that
spontaneously cyclizes to a neurotoxic phosphate (saligenin phosphate ester)
ignited the interest in this group of compounds. Only the ortho isomer can
cyclize and clinically cause Organo Phosphate Induced Delayed Neurotoxicity
(OPIDN); the meta and para isomers of tri-cresyl phosphate are not neuropathic
because they are unable to form stable cyclic saligenin phosphate esters. This
review identifies the diverse biological effects associated with various cyclic
and caged phosphates and phosphonates and their possible use. Cyclic compounds
that inhibit acetylcholine esterase (AChE), such as salithion, can be employed as
pesticides. Others are neurotoxic, most probably because of inhibition of
neuropathy target esterase (NTE). Cyclic phosphates that inhibit lipases, the
cyclipostins, possibly represent promising therapeutic avenues for the treatment
of type 2 diabetes mellitus and/or microbial infections; those compounds
inhibiting beta-lactamase may prevent bacterial resistance against beta-lactam
antibiotics. Naturally occurring cyclic phosphates, such as cyclic AMP, cyclic
phosphatidic acid and the ryanodine receptor modulator cyclic adenosine
diphosphate ribose, play an important physiological role in signal transduction.
Moreover, some cyclic phosphates are GABA-antagonists, while others are an
essential component of Molybdenum-containing enzymes. Some cyclic phosphates
(cyclophosphamide, ifosfamide) are clinically used in tumor therapy, while the
coupling of therapeutic agents with other cyclic phosphates (HepDirect(r)
Technology) allows drugs to be targeted to specific organs. Possible clinical
applications of these compounds are considered. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27612210
TI - An Easily Accessed Nickel Nanoparticle Catalyst for Alkene Hydrosilylation with
Tertiary Silanes.
AB - The first efficient and non-precious nanoparticle catalyst for alkene
hydrosilylation with commercially relevant tertiary silanes has been developed.
The nickel nanoparticle catalyst was prepared in situ from a simple nickel
alkoxide precatalyst Ni(O(t) Bu)2 ?x KCl. The catalyst exhibits high activity for
anti-Markovnikov hydrosilylation of unactivated terminal alkenes and isomerizing
hydrosilylation of internal alkenes. The catalyst can be applied to synthesize a
single terminal alkyl silane from a mixture of internal and terminal alkene
isomers, and to remotely functionalize an internal alkene derived from a fatty
acid.
PMID- 27612209
TI - Defense traits in the long-lived Great Basin bristlecone pine and resistance to
the native herbivore mountain pine beetle.
AB - Mountain pine beetle (MPB, Dendroctonus ponderosae) is a significant mortality
agent of Pinus, and climate-driven range expansion is occurring. Pinus defenses
in recently invaded areas, including high elevations, are predicted to be lower
than in areas with longer term MPB presence. MPB was recently observed in high
elevation forests of the Great Basin (GB) region, North America. Defense and
susceptibility in two long-lived species, GB bristlecone pine (Pinus longaeva)
and foxtail pine (P. balfouriana), are unclear, although they are sympatric with
a common MPB host, limber pine (P. flexilis). We surveyed stands with sympatric
GB bristlecone-limber pine and foxtail-limber pine to determine relative MPB
attack susceptibility and constitutive defenses. MPB-caused mortality was
extensive in limber, low in foxtail and absent in GB bristlecone pine. Defense
traits, including constitutive monoterpenes, resin ducts and wood density, were
higher in GB bristlecone and foxtail than in limber pine. GB bristlecone and
foxtail pines have relatively high levels of constitutive defenses which make
them less vulnerable to climate-driven MPB range expansion relative to other high
elevation pines. Long-term selective herbivore pressure and exaptation of traits
for tree longevity are potential explanations, highlighting the complexity of
predicting plant-insect interactions under climate change.
PMID- 27612211
TI - Neonatal progeriod syndrome associated with biallelic truncating variants in
POLR3A.
AB - Wiedemann-Rautenstrauch syndrome, also known as neonatal progeroid syndrome, is a
rare condition with fewer than 40 patients reported in the literature.
Characteristic physical findings include neonatal progeroid appearance, sparse
scalp hair, prominent scalp veins, and lipoatrophy; in addition, neonatal teeth
are often a distinctive finding. The inheritance pattern of this disorder has
been postulated to be autosomal recessive, although a specific gene has not been
identified. Here we report an infant with the characteristic phenotypic features
of Wiedemann-Rautenstrauch syndrome in whom exome sequencing identified two
pathogenic variants in POLR3A: c.1909+18G>A; p.(Y637Cfs*23) and c.2617C>T;
p.(R873*). Mutations in POLR3A (OMIM #614258) are associated with 4H
leukodystrophy syndrome characterized by the triad of hypomyelination,
hypodontia, and hypogonadotrophic hypogonadism. The present patient's genotype
implies a broader phenotypic range for POLR3A mutations and might expand the
clinical spectrum. This proband is notable because she had two null pathogenic
variants. Replication in other patients clinically diagnosed with Wiedemann
Rautenstrauch syndrome is needed to further demonstrate this gene-disease
association. (c) 2016 Wiley Periodicals, Inc.
PMID- 27612212
TI - Sexual functioning before and after vaginal hysterectomy to treat pelvic organ
prolapse and the effects of vaginal cuff closure techniques: a prospective
randomised study.
AB - OBJECTIVE: To evaluate sexual function in women before and after vaginal
hysterectomy (VH) and to compare the effects of horizontal and vertical vaginal
cuff closure on sexual function. STUDY DESIGN: Women with uterine prolapse of
stage 2 or higher were included to this prospective, randomized study. All
patients underwent VH with McCall Culdoplasty and patients were randomized into
two groups in terms of the vaginal cuff closure technique employed which is
either vertically (group 1, right to left) or horizontally (group 2, anterior to
posterior). Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire-12
Short Form was used to assess sexual function before and 6 months after surgery.
RESULTS: A total of 78 women participated, 37 in group 1 and 41 in group 2.
Significant improvements in were thus evident in both groups 1 (p=0.000) and 2
(p=0.000) after surgery; no significant between-group differences were evident.
Overall, 61 women (78,2%) had improved PISQ-12 scores postoperatively, 11 (14,1%)
scored the same pre- and post-operatively, and 6 (7,9%) scored lower
postoperatively. Women who reported poorer sexual function postoperatively, or no
improvement, had new-onset or worsening dyspareunia and/or incontinence.
CONCLUSION: Most women with uterine prolapse of stage 2 or higher who underwent
VH with prolapse repair experienced improved sexual lives postoperatively,
regardless of the cuff closure technique used. Although VH to treat POP improves
anatomical and sexual concerns, surgery per se may have negative effects on
sexual function if new-onset or worsening dyspareunia or incontinence develop.
PMID- 27612213
TI - Maternal cardiac deceleration capacity: a novel insight into maternal autonomic
function in pregnancies complicated by hypertensive disorders and intrauterine
growth restriction.
AB - OBJECTIVE: To explore maternal cardiac deceleration capacity (DC), a marker of
autonomic function derived from electrocardiographic (ECG) signals, in
pregnancies complicated by intrauterine growth restriction (IUGR) and
hypertensive disorders of pregnancy (HDP) associated to IUGR (HDP-IUGR) or to
appropriate for gestational age fetal growth (HDP-AGAf). METHODS: Prospective
single center case-control study conducted at Buzzi Children's Hospital, Milan.
Maternal ECGs were analyzed by Phase Rectified Signal Averaging (PRSA) method to
obtain cardiac DC in women with: HDP-IUGR, HDP-AGAf, severe-IUGR, mild-IUGR and
uncomplicated pregnancies. IUGR was defined as abdominal circumference <5th
centile; severe-IUGR was associated with umbilical artery Doppler pulsatility
index >2 standard deviations. Non-parametric tests were adopted. RESULTS: 269
women were recruited. Women with HDP-IUGR (n=35) showed significantly higher
cardiac DC compared both to controls (n=141) (p=0.003) and women with HDP-AGAf
(n=18) (p=0.01). Women with severe-IUGR (n=14) showed significantly higher DC
than controls (p=0.01). Women with mild-IUGR (n=61) as well as women with HDP
AGAf showed no differences in DC compared to controls (both p=0.3). CONCLUSIONS:
Women with pregnancy complicated by severe placental failure, such as HDP-IUGR
and severe IUGR, show significant autonomic alterations, as indicated by elevated
cardiac DC. On the contrary, pregnancy complications such as HDP-AGAf and mild
IUGR show no impact on maternal autonomic balance. We present a new approach to
explore maternal autonomic cardiovascular regulation that might reflect the
severity of placental vascular insufficiency.
PMID- 27612214
TI - Outcomes of pelvic arterial embolization in the management of postpartum
haemorrhage: a case series study and systematic review.
AB - BACKGROUND: Postpartum haemorrhage (PPH) is an unpredictable obstetric emergency
that requires a multidisciplinary approach. Pelvic arterial embolization (PAE) is
considered as a second-line treatment, although the published results have not
been reviewed systematically since 2007. OBJECTIVES: To evaluate success and
complication rates of PAE to treat PPH in the study hospital between 2009 and
2015, and to perform a systematic review of the literature on the reported
efficacy and safety of PAE for the management of PPH. SEARCH STRATEGY: A
systematic review of articles on PAE in English or Spanish was conducted using
Medline and the Cochrane Library. SELECTION CRITERIA: All published articles
assessing success and complication rates of PAE in cases of PPH. The search was
restricted to articles published in English or Spanish between 2000 and 2015,
with at least 25 cases. DATA COLLECTION AND ANALYSIS: Obstetric variables,
maternal haemodynamic state, pre-/postembolization management, technique-related
variables, post-PAE evolution and complications were recorded in the case series
study. Study characteristics, success rates and PAE-related complication rates
were recorded in the systematic review. MAIN RESULTS: The case series included 29
patients. The majority of these patients were primiparous, with singleton term
pregnancies and spontaneous labour. Caesarean section was performed in 62.1% of
patients undergoing PAE for PPH. PAE was successful in 89.6% [95% confidence
interval (CI) 78.3-100] of cases. Twenty studies were included in the systematic
review, providing data from 1739 patients. PAE was successful in 89.4% (95% CI
87.9-90.9) of cases. The mortality rate was 0.9%, and other major complications
were uncommon (1.8%). CONCLUSIONS: PAE was found to be a minimally invasive,
highly successful and safe technique for the management of PPH. It should be
considered in PPH refractory to initial treatment.
PMID- 27612215
TI - Repair Rate of Clustered Abasic DNA Lesions by Human Endonuclease: Molecular
Bases of Sequence Specificity.
AB - In the present contribution, the interaction between damaged DNA and repair
enzymes is examined by means of molecular dynamics simulations. More
specifically, we consider clustered abasic DNA lesions processed by the primary
human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in
stark contrast with the corresponding bacterial endonucleases, human APE1 imposes
strong geometrical constraints on the DNA duplex. As a consequence, the level of
recognition and, hence, the repair rate is higher. Important features that guide
the DNA/protein interactions are the presence of an extended positively charged
region and of a molecular tweezers that strongly constrains DNA. Our results are
on very good agreement with the experimentally determined repair rate of
clustered abasic lesions. The lack of repair for one particular arrangement of
the two abasic sites is also explained considering the peculiar destabilizing
interaction between the recognition region and the second lesion, resulting in a
partial opening of the molecular tweezers and, thus, a less stable complex. This
contribution cogently establishes the molecular bases for the recognition and
repair of clustered DNA lesions by means of human endonucleases.
PMID- 27612216
TI - Effects of mycoplasmal pneumonia of swine (MPS) lung lesion-selected Landrace
pigs on MPS resistance and immune competence in three-way crossbred pigs.
AB - To clarify the genetic influence of mycoplasmal pneumonia of swine (MPS) lesion
selected Landrace (La) on MPS resistance and immune characteristics in three-way
crossbred pigs (LaWaDa), the LaWaDa pigs were compared with the non-selected
crossbred (LbWbDb) and purebred (La) pigs. The MPS lesion score in the three
lines was as follows: La line < LaWaDa line < LbWbDb line, with significant
differences among the lines. The proportions of myeloid cells and T cells were
lower and higher, respectively, in the LaWaDa pigs compared with those in the
other two lines. Messenger RNA (mRNA) expression of interleukin (IL)-6, IL-10,
transforming growth factor-beta, and interferon-gamma in peripheral blood was
significantly increased after vaccination in the La and LaWaDa lines. IL-4 mRNA
expression in the LaWaDa line was intermediate to the La and LbWbDb lines.
Furthermore, principal component analysis for immune traits and MPS lesions was
executed to clarify the characteristics of each pig line. These findings suggest
that the immune responses in the three pig lines are genetically distinct and
that MPS resistance and some immunity characteristics from the La line were
transmitted to the three-way crossbred pigs.
PMID- 27612217
TI - Endoscopic ultrasound-guided drainage of abdominal fluid collections after
pancreatic surgery: Efficacy and long-term follow-up.
AB - BACKGROUND/PURPOSE: Endoscopic ultrasound-guided drainage (EUS-GD) of
postoperative abdominal fluid collections (POFC) following pancreatic surgery is
used as an alternative or complement to percutaneous drainage (PD) procedure. The
present single-center retrospective study evaluates its efficacy and safety.
METHOD: We included consecutive cases with POFC treated by EUS-GD between
September 2009 and November 2014 in our department. Technical success, long-term
clinical success, recurrence rate and need for surgery were analyzed. RESULTS: 24
procedures in 20 patients (95 % after pancreatic resection) were assessed.
Indications for surgery included tumors/lesions located in the pancreas (15/20),
chronic pancreatitis (3/20) and duodenal adenoma not completely resectable
endoscopically (2/20). EUS-GD was performed within a median of 30 days (IQR:
8.25) for a median fluid collection size of 72.5 mm (IQR: 46.25), requiring a
mean of 1.2 sessions with placement of a mean of 2.1 plastic stents (7 Fr/10 Fr)
per patient for a mean of 89 days (IQR: 127). Microbiology of aspirated fluid
revealed positive cultures in 13 patients, mostly polymicrobial, isolated
positive for fungal and 3 multidrug-resistant gram negative (MRGN) in 4 cases. An
additional transpapillary drainage was inserted in 1/20 patients. 4/20 patients
received PD, mostly before EUS-GD. Technical and clinical success was achieved in
20/20 (100 %) and 18/20 (90 %) patients, respectively, while 2 patients required
re-operation. During follow-up (median 630 days after stent removal, range: 45 -
2160), recurrence occurred in 1/18 (5.5 %) patient that was referred for surgery.
No death or severe adverse events were noted. CONCLUSION: EUS-GD is an effective,
minimally invasive and safe method for therapy of POFC after pancreatic surgery
offering long-term remission in about 95 % of cases.
PMID- 27612218
TI - Causes of altered liver function tests - the role of alpha-1 antitrypsin.
AB - BACKGROUND: Altered liver function tests are a common finding in clinical
practice. Our retrospective study aimed to identify the diagnoses in a non
selected cohort of patients with altered liver tests and to investigate whether
alpha-1 antitrypsin genotyping should be part of the diagnostic workup. PATIENTS
AND METHODS: 501 patients who were admitted to our outpatient clinic for further
evaluation of altered liver function tests were included in the study. The
patients underwent a standardized diagnostic program with history taking,
physical examination, laboratory tests and ultrasonography. Liver biopsy was
performed if appropriate. RESULTS: More than 50 % of the patients had
nonalcoholic fatty liver disease. Alcoholic and drug-induced liver injury were
found in 8.6 % and 7 % of patients, respectively. Chronic hepatitis B and C,
autoimmune liver disease and inherited causes of liver disease made up for
approximately 16 % of the diagnoses. The remaining patients were diagnosed with
kryptogenic liver disease or had miscellaneous diagnoses. In 3.7 % of the
genotyped patients, the alpha-1 antitrypsin genotype PiMZ was found. CONCLUSION:
Nonalcoholic fatty liver disease is nowadays the most frequent cause of altered
liver tests. Alcoholic liver disease might be underrepresented in our study since
these patients less often seek medical attention or the diagnosis is already made
by the primary care physician. Drug-induced liver injury was found in more
patients than expected and might therefore be underdiagnosed in practice. The
alpha-1 antitrypsin genotype PiMZ was found in absence of other possible causes
of liver disease, indicating that the PiMZ genotype is itself a risk factor for
liver disease. Genotyping for alpha-1 antitrypsin should therefore be done when
other causes for altered liver function tests have been ruled out.
PMID- 27612219
TI - Esophageal function tests are not helpful in symptoms suspicious of
extraesophageal reflux - a prospective study in 74 patients.
AB - BACKGROUND/AIMS: Symptoms suspicious of extraesophageal reflux (SSEER) include
globus, chronic cough, mucous obstruction and hoarseness. Reports of conventional
esophageal function tests and measurement of extraesophageal reflux (EER) in
these patients are spare providing conflicting results. METHODS: In a prospective
study we evaluated 60 patients with SSEER by esophageal function tests
(esophageal manometry, combined 24 h pH - metry - impedance and oropharyngeal pH
measurement, Dx - pH measurement) and esophagogastroduodenoscopy (EGD). The
patients were stratified into 2 groups according to their accompanying reflux
symptoms. Group 1, n = 23, comprised patients with SSEER solely and group 2, n =
37 patients with SSEER and reflux symptoms. The patients were compared to
patients with reflux symptoms solely (group 3, n = 14). RESULTS: There were no
significant differences between the groups according to age, sex and BMI.
Patients with SSEER and reflux symptoms (group 2) showed significantly increased
proportion of pathological acid reflux, de Meester Score, pH < 4 overall and in
upright positon and hypotensive lower esophageal sphincter pressure compared to
patients with SSEER solely (group 1) but no significant difference to patients
with reflux symptoms solely (group 3). All the other parameters of esophageal
testing including non-acid reflux and EER were not significantly different
between the three groups. CONCLUSION: The results of the present study do not
support a causal link between SSEER and esophageal motility disorders, acid or
non-acid reflux and EER as measured by conventional esophageal function tests and
oropharyngeal pH measurement.
PMID- 27612220
TI - [Long-term HR-Manometry of the Esophagus: first findings in clinical use].
AB - Diagnosis of oesophageal motility disorders has been well established for many
years now, although circadian gastrointestinal motility is still purely
understood. So far, high-resolution manometry (HRM) is only available for short
term measurement in clinical practice to evaluate simultaneous pressure
conditions throughout the esophagus. Thus, only a very limited period of time can
be investigated. There is evidence that disorders in esophageal motility can
cause severe discomfort and symptoms even though they only tend to occur
spontaneously. When performing short-term-measurements, these often cannot be
detected. Therefore, one can assume that long-term analysis of the esophageal
function will provide valuable new insights, which will contribute to more
effective medicamenteous and operative treatment in esophageal motility
disorders. At our gastrointestinal functional diagnostic laboratory, it has been
possible to perform high-resolution manometry over the period of 24 hours since
June 2014. We used a manometric probe consisting of 36 pressure sensors which are
connected to a mobile recording device for ambulatory measurement. This article
describes our experiences in clinical use when performing long-term high
resolution manometry and discusses usability and relevance of the results in the
context of the underlying esophageal motility disorder.
PMID- 27612221
TI - [A 22-year-old mother with severe pruritus and increasing jaundice two weeks
after starting hormonal contraception].
AB - Intermittent cholestatic liver disease may indicate an inherited deficiency of
bile salt transport proteins. Episodes of cholestasis may start during pregnancy
or during use of oral contraceptives or other medication. We describe the case of
a 22-year-old mother with increasing jaundice and severe pruritus two weeks after
starting hormonal contraception. A few months before she was suffering from
intrahepatic cholestasis of pregnancy (ICP). Liver biopsy showed bland
cholestasis with canalicular bile plugs. Treatment with ursodeoxycholic acid was
not effective. Finally, rifampicin induced a complete remission of the
cholestasis. Genetic testing showed a heterozygous mutation in the ABCB11 gene
encoding the bile salt export pump (BSEP). Rifampicin activates nuclear receptors
and may induce alternative pathways for the excretion of bile salts in patients
with ABCB11 deficiency.
PMID- 27612223
TI - [Not Available].
PMID- 27612222
TI - Yellow fever vaccination during treatment with infliximab in a patient with
ulcerative colitis: A case report.
AB - We report the case of a 59-year-old patient who accidentally underwent live
vaccination against yellow fever during continuous treatment with the TNF-alpha
antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever
of short duration and elevation of liver enzymes without further clinical
complications. Yellow fever viremia was not detectable and protective antibodies
were developed. A primary vaccination against yellow fever under infliximab has
not been reported in the literature before, although vaccination is an important
topic in IBD. Live vaccinations, like Stamaril((r)) against yellow fever, are
contraindicated during TNF-alpha-AB treatment. Treatment regimens containing TNF
alpha-AB are of growing importance, not only in gastroenterology, but also in
rheumatology and dermatology. We discuss this topic by presenting our case and
reviewing the current literature.
PMID- 27612224
TI - An EMBO workshop on Emerging Concepts of the Neuronal Cytoskeleton: A unique
venue to discuss recent advances in cellular and molecular aspects of
cytoskeleton function in nerve cells.
PMID- 27612225
TI - Local adaptation of plant viruses: lessons from experimental evolution.
AB - For multihost pathogens, adaptation to multiple hosts has important implications
for both applied and basic research. At the applied level, it is one of the main
factors determining the probability and severity of emerging disease outbreaks.
At the basic level, it is thought to be a key mechanism for the maintenance of
genetic diversity both in host and pathogen species. In recent years, a number of
evolution experiments have assessed the fate of plant virus populations
replicating within and adapting to one single or to multiple hosts species. A
first group of these experiments tackled the existence of trade-offs in fitness
and virulence for viruses evolving either within a single hosts species or
alternating between two different host species. A second set of experiments
explored the role of genetic variability in susceptibility and resistance to
infection among individuals from the same host species in the extent of virus
local adaptation and of virulence. In general, when a single host species or
genotype is available, these experiments show that local adaptation takes place,
often but not always associated with a fitness trade-off. However, alternating
between different host species or infecting resistant host genotypes may select
for generalist viruses that experience no fitness cost. Therefore, the expected
cost of generalism, arising from antagonistic pleiotropy and other genetic
mechanisms generating fitness trade-offs between hosts, could not be generalized
and strongly depend on the characteristics of each particular pathosystem. At the
genomic level, these studies show pervasive convergent molecular evolution,
suggesting that the number of accessible molecular pathways leading to adaptation
to novel hosts is limited.
PMID- 27612279
TI - Cancer co-occurrence patterns in Parkinson's disease and multiple sclerosis-Do
they mirror immune system imbalances?
AB - BACKGROUND: To examine the site-specific cancer mortality among deaths registered
with Parkinson's disease (PD) and multiple sclerosis (MS). We focused on the
patterns related to the most frequent cancers. METHODS: We analyzed Swiss
mortality data over a 39-year period (1969-2007), using a statistical approach
applicable to unique daabases, i.e. when no linkage with morbidity databases or
disease registries is possible. It was based on a case-control design with
bootstrapping to derive standardized mortality ratios (SMR). The cases were
defined by the cancer-PD or cancer-MS co-registrations, whereas the controls were
drawn from the remaining records with cancer deaths (matching criteria: sex, age,
language region of Switzerland, subperiods 1969-1981, 1982-1994, 1995-2007).
RESULTS: For PD we found lower SMRs in lung and liver cancer and higher SMRs in
melanoma/skin cancer, and in cancers of breast and prostate. As for MS, the SMR
in lung cancer was lower than expected, whereas SMRs in colorectal, breast and
bladder cancer were higher. CONCLUSIONS: A common pattern of associations can be
observed in PD and MS, with a lower risk of lung cancer and higher risk of breast
cancer than expected. Thus, PD and MS resemble other conditions with similar
(schizophrenia) or reversed patterns (rheumatoid arthritis, immunosuppression
after organ transplantation).
PMID- 27612280
TI - RNA-targeted therapeutics in cancer clinical trials: Current status and future
directions.
AB - Recent advances in RNA delivery and target selection provide unprecedented
opportunities for cancer treatment, especially for cancers that are particularly
hard to treat with existing drugs. Small interfering RNAs, microRNAs, and
antisense oligonucleotides are the most widely used strategies for silencing gene
expression. In this review, we summarize how these approaches were used to
develop drugs targeting RNA in human cells. Then, we review the current state of
clinical trials of these agents for different types of cancer and outcomes from
published data. Finally, we discuss lessons learned from completed studies and
future directions for this class of drugs.
PMID- 27612281
TI - Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of
Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors.
AB - Abaloparatide-SC is a novel 34-amino acid peptide created to be a potent and
selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling
pathway. In the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE)
Phase 3 trial (NCT01343004), abaloparatide reduced new morphometric vertebral
fractures by 86% compared with placebo (p < 0.001) and nonvertebral fractures by
43% (p = 0.049) in postmenopausal women with osteoporosis. Abaloparatide-SC
increased bone mineral density (BMD) 3.4% at the total hip, 2.9% at the femoral
neck, and 9.2% at the lumbar spine at 18 months (all p < 0.001 versus placebo).
The analysis reported here was designed to evaluate whether fracture risk
reductions and BMD accrual were consistent across different levels of baseline
risk. Risk factor subgroups were predefined categorically for BMD T-score of the
lumbar spine, total hip, and femoral neck (<=-2.5 versus >-2.5 and <=-3.0 versus
>-3.0), history of nonvertebral fracture (yes versus no), prevalent vertebral
fracture (yes versus no), and age (<65 versus 65 to <75 versus >=75 years) at
baseline. Forest plots show that there were no clinically meaningful interactions
between any of the baseline risk factors and the treatment effect of
abaloparatide-SC on new morphometric vertebral fractures, nonvertebral fractures,
or BMD increases. Abaloparatide provides protection against fractures
consistently across a wide variety of ages and baseline risks, including those
with and without prior fractures, and it has potential utility for a broad group
of postmenopausal women with osteoporosis. (c) 2016 American Society for Bone and
Mineral Research.
PMID- 27612282
TI - Postoperative Radiation Therapy after Nipple-Sparing or Skin-Sparing Mastectomy:
A Survey of European, North American, and South American Practices.
AB - Skin sparing mastectomy, a surgical procedure sparing a large portion of the
overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole
nipple-areolar complex, are increasingly used, although their oncologic efficacy
remains unclear. The aim of this study was to assess the radiation oncologists'
opinions regarding the indications of radiation therapy (RT) after skin-sparing
mastectomy and nipple-sparing mastectomy. Radiation oncology members of four
national and international societies were invited to complete a questionnaire
comprising of 22 questions to assess their opinions regarding RT indications in
the context of skin-sparing and nipple-sparing mastectomy. A total of 298
radiation oncologists answered the questionnaire. 90.9% of respondents affirmed
that breast cancer is one of their specializations. The majority declared that
post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer
patients who present with risk factors for recurrence after skin-sparing or
nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk
factors (tumor size, lymph node involvement, extracapsular extension,
lymphovascular space invasion, positive surgical margins, triple negative tumor,
multicentric tumor, and age) were considered as major elements (important or very
important). There is no consensus regarding the necessity of evaluating residual
breast tissue or the definition of residual breast tissue after mastectomy. All
classic factors were considered as major elements, potentially influencing the
decision to advice or not postoperative RT. Many uncertainties remain about the
indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy.
PMID- 27612284
TI - Practical Application of Anatomy of the Oral Cavity in Forensic Facial
Reconstruction.
AB - The oral cavity's importance in defining the facial region makes it a primary
feature for forensic facial reconstruction (FFR). The aim of this study is to
construct a pattern of reference for dimensions and proportions of the lips and
establish parameters that may help estimate the vermilion borders' height
dimensions and the mouth's width. By means of cone beam computed tomography,
divided into two samples: sample 1 (n = 322; 137 male, 185 female) verified the
linear distances delimited by anatomical landmarks in soft tissue. The sample 2
(n = 108; 40 male, 68 female), verified the proportions among the height of the
vermilion borders, width of the mouth, and linear distances between craniometric
landmarks in hard tissues, both from a Brazilian database. The measurements were
completed using OsiriX, and the results were analyzed by means of descriptive
statistics at a level of significance of 5%. The height of the vermilion borders
corresponded to approximately 26% of the width of the mouth. The width of the
mouth increased over the course of time in men and remained stable in women. In
men, a mean intercanine distance of 75% of the total mouth's width was found; for
women, it was 80%. The parameters of the relations between soft and hard tissues
in the oral cavity region presented that the distance between landmarks ID-SM
(Infradentale-Supramentale) corresponded to 55% of the height of the vermilion
borders of the mouth for both sexes, while the distance between landmarks PM-SD
(Philtrum medium-Supradentale) corresponded to 85% in men and 88% in women. Mean
values of 97% of the width of the mouth in women and 93% in men were attributed
to the distance between the mentonian foramina. It was not possible to estimate
the height of the labial vermilion borders by the bone measurements, FIs-Fli
(Foramen incisivus superius-inferius) and NS-GN (Nasospinale-Gnathion). Profound
knowledge of the anatomy and morphology of the oral cavity may contribute to
increasing the precision of FFRs and help with human identification.
PMID- 27612283
TI - A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits
Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo.
AB - Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and
fatal degenerative disease resulting from persistent measles virus (MV) infection
of the central nervous system. Most drugs used to treat SSPE have been reported
to have limited effects. Therefore, novel therapeutic strategies are urgently
required. The SSPE virus, a variant MV strain, differs virologically from wild
type MV strain. One characteristic of the SSPE virus is its defective production
of cell-free virus, which leaves cell-to-cell infection as the major mechanism of
viral dissemination. The fusion protein plays an essential role in this cell-to
cell spread. It contains two critical heptad repeat regions that form a six-helix
bundle in the trimer similar to most viral fusion proteins. In the case of human
immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the
heptad repeat region of the fusion protein enfuvirtide inhibits viral replication
and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of
HIV-1 are structurally and functionally similar to those of the MV fusion
protein. We therefore designed novel peptides derived from the fusion protein
heptad repeat region of the MV and examined their effects on the measles and SSPE
virus replication in vitro and in vivo. Some of these synthetic novel peptides
demonstrated high antiviral activity against both the measles (Edmonston strain)
and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no
cytotoxicity in vitro. In particular, intracranial administration of one of the
synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus
infected nude mouse model.
PMID- 27612285
TI - Yttrium-Doped Sb2Te3: A Promising Material for Phase-Change Memory.
AB - Sb2Te3 exhibits outstanding performance among the candidate materials for phase
change memory; nevertheless, its low electrical resistivity and thermal stability
hinder its practical application. Hence, numerous studies have been carried out
to search suitable dopants to improve the performance; however, the explored
dopants always cause phase separation and thus drastically reduce the reliability
of phase-change memory. In this work, on the basis of ab initio calculations, we
have identified yttrium (Y) as an optimal dopant for Sb2Te3, which overcomes the
phase separation problem and significantly increases the resistivity of
crystalline state by at least double that of Sb2Te3. The good phase stability of
crystalline Y-doped Sb2Te3 (YST) is attributed to the same crystal structure
between Y2Te3 and Sb2Te3 as well as their tiny lattice mismatch of only ~1.1%.
The significant increase in resistivity of c-YST is understood by our findings
that Y can dramatically increase the carrier's effective mass by regulating the
band structure and can also reduce the intrinsic carrier density by suppressing
the formation of SbTe antisite defects. Y doping can also improve the thermal
stability of amorphous YST based on our ab initio molecular dynamics simulations,
which is attributed to the stronger interactions between Y and Te than that of Sb
and Te.
PMID- 27612286
TI - The cytological features of CAR(T) cells.
PMID- 27612289
TI - Which advises for primary food allergy prevention in normal or high-risk infant?
AB - In the last decades, international guidelines proposed different strategies of
complementary foods introduction during weaning to prevent allergy. Avoidance
measures, such as late introduction of allergenic foods, failed to show a
significant preventive effect towards allergy. Recently, prospective randomized
controlled studies suggested that the early introduction of solid foods - rather
than the late introduction - could be a strategy to prevent allergic
sensitization and food allergy. However, at today clear evidence of effectiveness
and safety of early introduction are not yet available to recommend a radical
change in the current clinical practice. A realistic advice for the general
population could be to begin the weaning at 4-5 months with the progressive
introduction of different foods. The advices for introduction of solid foods
during weaning should also take in consideration the global development of child
to chose the better timing of introduction of foods.
PMID- 27612288
TI - Digital Droplet PCR for the Absolute Quantification of Exon Skipping Induced by
Antisense Oligonucleotides in (Pre-)Clinical Development for Duchenne Muscular
Dystrophy.
AB - Antisense oligonucleotides (AONs) in clinical development for Duchenne muscular
dystrophy (DMD) aim to induce skipping of a specific exon of the dystrophin
transcript during pre-mRNA splicing. This results in restoration of the open
reading frame and consequently synthesis of a dystrophin protein with a shorter
yet functional central rod domain. To monitor the molecular therapeutic effect of
exon skip-inducing AONs in clinical studies, accurate quantification of pre- and
post-treatment exon skip levels is required. With the recent introduction of 3rd
generation digital droplet PCR (ddPCR), a state-of-the-art technology became
available which allows absolute quantification of transcript copy numbers with
and without specific exon skip with high precision, sensitivity and
reproducibility. Using Taqman assays with probes targeting specific exon-exon
junctions, we here demonstrate that ddPCR reproducibly quantified cDNA fragments
with and without exon 51 of the DMD gene over a 4-log dynamic range. In a
comparison of conventional nested PCR, qPCR and ddPCR using cDNA constructs with
and without exon 51 mixed in different molar ratios using, ddPCR quantification
came closest to the expected outcome over the full range of ratios (0-100%),
while qPCR and in particular nested PCR overestimated the relative percentage of
the construct lacking exon 51. Highest accuracy was similarly obtained with ddPCR
in DMD patient-derived muscle cells treated with an AON inducing exon 51
skipping. We therefore recommend implementation of ddPCR for quantification of
exon skip efficiencies of AONs in (pre)clinical development for DMD.
PMID- 27612290
TI - Aspergillus: An uncommon pathogen of eumycetoma.
PMID- 27612287
TI - Inflamed In Vitro Retina: Cytotoxic Neuroinflammation and Galectin-3 Expression.
AB - BACKGROUND: Disease progression in retinal neurodegeneration is strongly
correlated to immune cell activation, which may have either a neuroprotective or
neurotoxic effect. Increased knowledge about the immune response profile and
retinal neurodegeneration may lead to candidate targets for treatments.
Therefore, we have used the explanted retina as a model to explore the immune
response and expression of the immune modulator galectin-3 (Gal-3), induced by
the cultivation per se and after additional immune stimulation with
lipopolysaccharide (LPS), and how this correlates with retinal neurotoxicity.
METHODS: Post-natal mouse retinas were cultured in a defined medium. One group
was stimulated with LPS (100 ng/ml, 24 h). Retinal architecture, apoptotic cell
death, and micro- and macroglial activity were studied at the time of cultivation
(0 days in vitro (DIV)) and at 3, 4 and 7 DIV using morphological staining,
biochemical- and immunohistochemical techniques. RESULTS: Our results show that
sustained activation of macro- and microglia, characterized by no detectable
cytokine release and limited expression of Gal-3, is not further inducing
apoptosis additional to the axotomy-induced apoptosis in innermost nuclear layer.
An elevated immune response was detected after LPS stimulation, as demonstrated
primarily by release of immune mediators (i.e. interleukin 2 (IL-2), IL-6, KC/GRO
(also known as CLCX1) and tumour necrosis factor-alpha (TNF-alpha)), increased
numbers of microglia displaying morphologies of late activation stages as well as
Gal-3 expression. This was accompanied with increased apoptosis in the two
additional nuclear layers, and damage to retinal gross architecture. CONCLUSION:
We demonstrate that an immune response characterized by sustained and increased
release of cytokines, along with an increase in Gal-3 expression, is accompanied
by significant increased neurotoxicity in the explanted retina. Further
investigations using the current setting may lead to increased understanding on
the mechanisms involved in neuronal loss in retinal neurodegenerations.
PMID- 27612291
TI - Absolute quantification of microbial taxon abundances.
AB - High-throughput amplicon sequencing has become a well-established approach for
microbial community profiling. Correlating shifts in the relative abundances of
bacterial taxa with environmental gradients is the goal of many microbiome
surveys. As the abundances generated by this technology are semi-quantitative by
definition, the observed dynamics may not accurately reflect those of the actual
taxon densities. We combined the sequencing approach (16S rRNA gene) with robust
single-cell enumeration technologies (flow cytometry) to quantify the absolute
taxon abundances. A detailed longitudinal analysis of the absolute abundances
resulted in distinct abundance profiles that were less ambiguous and expressed in
units that can be directly compared across studies. We further provide evidence
that the enrichment of taxa (increase in relative abundance) does not necessarily
relate to the outgrowth of taxa (increase in absolute abundance). Our results
highlight that both relative and absolute abundances should be considered for a
comprehensive biological interpretation of microbiome surveys.
PMID- 27612292
TI - Changes in Medicare Shared Savings Program Savings From 2013 to 2014.
PMID- 27612294
TI - Extracorporeal photopheresis did not prevent the development of an autoimmune
disease: myasthenia gravis.
AB - BACKGROUND: Myasthenia gravis (MG) is a neuromuscular disorder characterized by
an autoimmune defect in the neuromuscular junction. In most patients, the
autoimmune attack is mediated by antibodies against the acetylcholine receptor
(AChR) on the postsynaptic membrane. Deficient immunoregulation, including
regulatory T cells, is consistently observed. Extracorporeal photopheresis (ECP)
leads to the induction of regulatory T cells that mediate immunologic tolerance
in autoimmune diseases; however, the data regarding MG are very limited. CASE
REPORT: Here, we report a patient who, during ongoing ECP therapy for his severe,
refractory, chronic graft-versus-host disease (cGVHD), developed MG, although he
responded very well to ECP, as indicated by the lowering of his chronic cGVHD
severity grade to moderate. RESULTS: Despite receiving ECP, our patient developed
MG, which was resistant to treatment and required intensive care unit support.
CONCLUSIONS: Close surveillance is required when ECP is planned as one of the
treatment alternatives in myasthenia gravis that develop in cGVHD.
PMID- 27612295
TI - Basking behavior predicts the evolution of heat tolerance in Australian
rainforest lizards.
AB - There is pressing urgency to understand how tropical ectotherms can behaviorally
and physiologically respond to climate warming. We examine how basking behavior
and thermal environment interact to influence evolutionary variation in thermal
physiology of multiple species of lygosomine rainforest skinks from the Wet
Tropics of northeastern Queensland, Australia (AWT). These tropical lizards are
behaviorally specialized to exploit canopy or sun, and are distributed across
marked thermal clines in the AWT. Using phylogenetic analyses, we demonstrate
that physiological parameters are either associated with changes in local thermal
habitat or to basking behavior, but not both. Cold tolerance, the optimal sprint
speed, and performance breadth are primarily influenced by local thermal
environment. Specifically, montane lizards are more cool tolerant, have broader
performance breadths, and higher optimum sprinting temperatures than their
lowland counterparts. Heat tolerance, in contrast, is strongly affected by
basking behavior: there are two evolutionary optima, with basking species having
considerably higher heat tolerance than shade skinks, with no effect of
elevation. These distinct responses among traits indicate the multiple selective
pressures and constraints that shape the evolution of thermal performance. We
discuss how behavior and physiology interact to shape organisms' vulnerability
and potential resilience to climate change.
PMID- 27612293
TI - Compared to Palliative Care, Working in Intensive Care More than Doubles the
Chances of Burnout: Results from a Nationwide Comparative Study.
AB - INTRODUCTION: Professionals working in intensive and palliative care units, hence
caring for patients at the end-of-life, are at risk of developing burnout.
Workplace conditions are determinant factors to develop this syndrome among
professionals providing end-of-life care. OBJECTIVES: To identify and compare
burnout levels between professionals working in intensive and palliative care
units; and to assess which workplace experiences are associated with burnout.
METHODS: A nationwide, multicentre quantitative comparative survey study was
conducted in Portugal using the following instruments: Maslach Burnout Inventory
Human Services Survey, Questionnaire of workplace experiences and ethical
decisions, and Questionnaire of socio-demographic and professional
characteristics. A total of 355 professionals from 10 intensive care and 9
palliative care units participated in the survey. A series of univariate and
multivariate logistic regression analyses were performed; odds ratio sidelong
with 95% confidence intervals were calculated. RESULTS: 27% of the professionals
exhibited burnout. This was more frequent in intensive care units (OR = 2.525,
95% CI: 1.025-6.221, p = .006). Univariate regression analyses showed that higher
burnout levels were significantly associated with conflicts, decisions to
withhold/withdraw treatment, and implementing palliative sedation. When
controlling for socio-demographic and educational characteristics, and setting
(intensive care units versus palliative care units), higher burnout levels were
significantly and positively associated with experiencing conflicts in the
workplace. Having post-graduate education in intensive/palliative care was
significantly but inversely associated to higher burnout levels. CONCLUSIONS:
Compared to palliative care, working in intensive care units more than doubled
the likelihood of exhibiting burnout. Experiencing conflicts (e.g., with patients
and/or families, intra and/or inter-teams) was the most significant determinant
of burnout and having post-graduate education in intensive/palliative care
protected professionals from developing this syndrome. This highlights the need
for promoting empowering workplace conditions, such as team empowerment and
conflict management. Moreover, findings suggest the need for implementing quality
improvement strategies and organizational redesign strategies aimed at
integrating the philosophy, principles and practices of palliative care in
intensive care units.
PMID- 27612297
TI - Therapeutic drug monitoring in the era of precision medicine: opportunities!
PMID- 27612298
TI - Wernicke's Encephalopathy in a Child with Acute Lymphoblastic Leukemia.
PMID- 27612299
TI - Bacterial microbiota associated with flower pollen is influenced by pollination
type, and shows a high degree of diversity and species-specificity.
AB - Diverse microorganisms colonise the different plant-microhabitats, such as
rhizosphere and phyllosphere, and play key roles for the host. However, bacteria
associated with pollen are poorly investigated, despite its ecological,
commercial and medical relevance. Due to structure and nutritive composition,
pollen provides a unique microhabitat. Here the bacterial abundance, community
structure, diversity and colonization pattern of birch, rye, rapes and autumn
crocus pollens were examined, by using cultivation, high-throughput sequencing
and microscopy. Cultivated bacteria belonged to Proteobacteria, Actinobacteria
and Firmicutes, with remarkable differences at species level between pollen
species. High-throughput sequencing of 16S rRNA gene amplicon libraries showed
Proteobacteria as the dominant phylum in all pollen species, followed by
Actinobacteria, Acidobacteria and Firmicutes. Both plant species and pollination
type significant influenced structure and diversity of the pollen microbiota. The
insect-pollinated species possessed a more similar microbiota in comparison to
the wind-pollinated ones, suggesting a levelling effect by insect vectors.
Scanning electron microscopy as well as fluorescent in situ hybridisation coupled
with confocal laser scanning microscopy (FISH-CLSM) indicated the tectum surface
as the preferred niche of bacterial colonisation. This work is the most
comprehensive study of pollen microbiology, and strongly increases our knowledge
on one of the less investigated plant-microhabitats.
PMID- 27612300
TI - Free-breathing volumetric fat/water separation by combining radial sampling,
compressed sensing, and parallel imaging.
AB - PURPOSE: Conventional fat/water separation techniques require that patients hold
breath during abdominal acquisitions, which often fails and limits the achievable
spatial resolution and anatomic coverage. This work presents a novel approach for
free-breathing volumetric fat/water separation. METHODS: Multiecho data are
acquired using a motion-robust radial stack-of-stars three-dimensional GRE
sequence with bipolar readout. To obtain fat/water maps, a model-based
reconstruction is used that accounts for the off-resonant blurring of fat and
integrates both compressed sensing and parallel imaging. The approach
additionally enables generation of respiration-resolved fat/water maps by
detecting motion from k-space data and reconstructing different respiration
states. Furthermore, an extension is described for dynamic contrast-enhanced fat
water-separated measurements. RESULTS: Uniform and robust fat/water separation is
demonstrated in several clinical applications, including free-breathing
noncontrast abdominal examination of adults and a pediatric subject with both
motion-averaged and motion-resolved reconstructions, as well as in a noncontrast
breast exam. Furthermore, dynamic contrast-enhanced fat/water imaging with high
temporal resolution is demonstrated in the abdomen and breast. CONCLUSION: The
described framework provides a viable approach for motion-robust fat/water
separation and promises particular value for clinical applications that are
currently limited by the breath-holding capacity or cooperation of patients. Magn
Reson Med 78:565-576, 2017. (c) 2016 International Society for Magnetic Resonance
in Medicine.
PMID- 27612301
TI - The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in
Neonatal Rat Ventricular Cardiomyocytes.
AB - The cardiac ryanodine receptor (RyR2) is an intracellular ion channel that
regulates Ca2+ release from the sarcoplasmic reticulum (SR) during excitation
contraction coupling in the heart. The glutathione transferases (GSTs) are a
family of phase II detoxification enzymes with additional functions including the
selective inhibition of RyR2, with therapeutic implications. The C-terminal half
of GSTM2 (GSTM2C) is essential for RyR2 inhibition, and mutations F157A and Y160A
within GSTM2C prevent the inhibitory action. Our objective in this investigation
was to determine whether GSTM2C can enter cultured rat neonatal ventricular
cardiomyocytes and influence contractility. We show that oregon green-tagged
GSTM2C (at 1 MUM) is internalized into the myocytes and it reduces spontaneous
contraction frequency and myocyte shortening. Field stimulation of myocytes
evoked contraction in the same percentage of myocytes treated either with media
alone or media plus 15 MUM GSTM2C. Myocyte shortening during contraction was
significantly reduced by exposure to 15 MUM GSTM2C, but not 5 and 10 MUM GSTM2C
and was unaffected by exposure to 15 MUM of the mutants Y160A or F157A. The
amplitude of the Ca2+ transient in the 15 MUM GSTM2C - treated myocytes was
significantly decreased, the rise time was significantly longer and the decay
time was significantly shorter than in control myocytes. The Ca2+ transient was
not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C
entering the myocytes and inhibiting RyR2, in a manner that indicates a possible
therapeutic potential for treatment of arrhythmia in the neonatal heart.
PMID- 27612302
TI - A Systematic Approach to Determining the Identifiability of Multistage
Carcinogenesis Models.
AB - Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time
Markov process models often used to relate cancer incidence to biological
mechanism. Identifiability analysis determines what model parameter combinations
can, theoretically, be estimated from given data. We use a systematic approach,
based on differential algebra methods traditionally used for deterministic
ordinary differential equation (ODE) models, to determine identifiable
combinations for a generalized subclass of MSCE models with any number of
preinitation stages and one clonal expansion. Additionally, we determine the
identifiable combinations of the generalized MSCE model with up to four clonal
expansion stages, and conjecture the results for any number of clonal expansion
stages. The results improve upon previous work in a number of ways and provide a
framework to find the identifiable combinations for further variations on the
MSCE models. Finally, our approach, which takes advantage of the Kolmogorov
backward equations for the probability generating functions of the Markov
process, demonstrates that identifiability methods used in engineering and
mathematics for systems of ODEs can be applied to continuous-time Markov
processes.
PMID- 27612303
TI - Ordered Peierls distortion prevented at growth onset of GeTe ultra-thin films.
AB - Using reflection high-energy electron diffraction (RHEED), the growth onset of
molecular beam epitaxy (MBE) deposited germanium telluride (GeTe) film on Si(111)
(?3 * ?3)R30 degrees -Sb surfaces is investigated, and a larger than expected in
plane lattice spacing is observed during the deposition of the first two
molecular layers. High-resolution transmission electron microscopy (HRTEM)
confirms that the growth proceeds via closed layers, and that those are stable
after growth. The comparison of the experimental Raman spectra with theoretical
calculated ones allows assessing the shift of the phonon modes for a quasi-free
standing ultra-thin GeTe layer with larger in-plane lattice spacing. The
manifestation of the latter phenomenon is ascribed to the influence of the
interface and the confinement of GeTe within the limited volume of material
available at growth onset, either preventing the occurrence of Peierls
dimerization or their ordered arrangement to occur normally.
PMID- 27612305
TI - Possible recent warming hiatus on the northwestern Tibetan Plateau derived from
ice core records.
AB - Many studies have reported enhanced warming trend on the Tibetan Plateau (TP),
even during the warming hiatus period. However, most of these studies are based
on instrumental data largely collected from the eastern TP, whereas the
temperature trend over the extensive northwestern TP remains uncertain due to few
meteorological stations. Here we combined the stable isotopic delta(18)O record
of an ice core recovered in 2012 from the Chongce glacier with the delta(18)O
records of two other ice cores (i.e., Muztagata and Zangser Kangri) in the same
region to establish a regional temperature series for the northwestern TP. The
reconstruction shows a significant warming trend with a rate of 0.74 +/- 0.12
degrees C/decade for the period 1970-2000, but a decreasing trend from 2001 to
2012. This is consistent with the reduction of warming rates during the recent
decade observed at the only two meteorological stations on the northwestern TP,
even though most stations on the eastern TP have shown persistent warming during
the same period. Our results suggest a possible recent warming hiatus on the
northwestern TP. This could have contributed to the relatively stable status of
glaciers in this region.
PMID- 27612304
TI - An In Vitro Approach to Study Effects of Prebiotics and Probiotics on the Faecal
Microbiota and Selected Immune Parameters Relevant to the Elderly.
AB - The aging process leads to alterations of gut microbiota and modifications to the
immune response, such changes may be associated with increased disease risk.
Prebiotics and probiotics can modulate microbiome changes induced by aging;
however, their effects have not been directly compared. The aim of this study was
to use anaerobic batch culture fermenters to assess the impact of various
fermentable carbohydrates and microorganisms on the gut microbiota and selected
immune markers. Elderly volunteers were used as donors for these experiments to
enable relevance to an aging population. The impact of fermentation supernatants
on immune markers relevant to the elderly were assessed in vitro. Levels of IL
1beta, IL-6, IL-8, IL-10 and TNF-alpha in peripheral blood mononuclear cell
culture supernatants were measured using flow cytometry. Trans
galactooligosaccharides (B-GOS) and inulin both stimulated bifidobacteria
compared to other treatments (p<0.05). Fermentation supernatants taken from
faecal batch cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus
and Ba. coagulans inhibited LPS induced TNF-alpha (p<0.05). IL-10 production,
induced by LPS, was enhanced by fermentation supernatants from faecal batch
cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus, Ba.
coagulans and Bac. thetaiotaomicron (p<0.05). To conclude, prebiotics and
probiotics could lead to potentially beneficial effects to host health by
targeting specific bacterial groups, increasing saccharolytic fermentation and
decreasing inflammation associated with aging. Compared to probiotics, prebiotics
led to greater microbiota modulation at the genus level within the fermenters.
PMID- 27612306
TI - Warming combined with more extreme precipitation regimes modifies the water
sources used by trees.
AB - The persistence of vegetation under climate change will depend on a plant's
capacity to exploit water resources. We analyzed water source dynamics in pinon
pine and juniper trees subjected to precipitation reduction, atmospheric warming,
and to both simultaneously. Pinon and juniper exhibited different and opposite
shifts in water uptake depth in response to experimental stress and background
climate over 3 yr. During a dry summer, juniper responded to warming with a shift
to shallow water sources, whereas pinon pine responded to precipitation reduction
with a shift to deeper sources in autumn. In normal and wet summers, both species
responded to precipitation reduction, but juniper increased deep water uptake and
pinon increased shallow water uptake. Shifts in the utilization of water sources
were associated with reduced stomatal conductance and photosynthesis, suggesting
that belowground compensation in response to warming and water reduction did not
alleviate stress impacts for gas exchange. We have demonstrated that predicted
climate change could modify water sources of trees. Warming impairs juniper
uptake of deep sources during extended dry periods. Precipitation reduction
alters the uptake of shallow sources following extended droughts for pinon.
Shifts in water sources may not compensate for climate change impacts on tree
physiology.
PMID- 27612307
TI - Calcium to phosphorus ratio, essential elements and vitamin D content of infant
foods in the UK: Possible implications for bone health.
AB - Adequate intake of calcium and phosphorus in the appropriate ratio of 1-2:1
(Ca:P), in addition to magnesium and vitamin D, is vital for bone health and
development of infants. In this feasibility study, the ratio of Ca:P in
conjunction with vitamin D and other essential elements (Cu, Fe, K, Mg, Na, and
Zn) in a range of commercial infant food products in the UK was investigated. The
elemental analysis was carried out using inductively coupled plasma optical
emission spectrometry, and vitamin D levels were determined using an enzyme
linked immunosorbent assay. The quantitative data were further evaluated, based
on a standardised menu, to measure the total daily intake of an infant aged 7-12
months against the Reference Nutrient Intake. The results from the study show
that the Ca:P ratio of the infant's total dietary intake was within the
recommended range at 1.49:1. However, the level of intake for each of the
nutrients analyzed, with the exception of sodium, was found to be above the
Reference Nutrient Intake, which warrants further investigation in relation to
both micronutrient interactions and in situations where the intake of fortified
infant formula milk is compromised. Finally, as the study is the first to include
consumption of infant snack products, the level of total calorie intake was also
calculated in order to assess the total daily estimated energy intake; the
results indicate that energy intakes exceed recommendations by 42%, which may
have implications for obesity.
PMID- 27612308
TI - Activity-Based Probes for 15-Lipoxygenase-1.
AB - Human 15-lipoxygenase-1 (15-LOX-1) plays an important role in several
inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well
as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and
stroke. Activity-based probes of 15-LOX-1 are required to explore the role of
this enzyme further and to enable drug discovery. In this study, we developed a
15-LOX-1 activity-based probe for the efficient activity-based labeling of
recombinant 15-LOX-1. 15-LOX-1-dependent labeling in cell lysates and tissue
samples was also possible. To mimic the natural substrate of the enzyme, we
designed activity-based probes that covalently bind to the active enzyme and
include a terminal alkene as a chemical reporter for the bioorthogonal linkage of
a detectable functionality through an oxidative Heck reaction. The activity-based
labeling of 15-LOX-1 should enable the investigation and identification of this
enzyme in complex biological samples, thus opening up completely new
opportunities for drug discovery.
PMID- 27612309
TI - A novel IGF2/H19 domain triplication in the 11p15.5 imprinting region causing
either Beckwith-Wiedemann or Silver-Russell syndrome in a single family.
AB - Defects of 11p15.5 imprinting result in two growth disorders with opposite
phenotypes: Beckwith-Wiedemann syndrome (BWS) characterized by overgrowth and
Silver-Russell syndrome (SRS) associated with growth retardation. In a small
group of patients with BWS and SRS, copy number variations (CNVs) involving the
11p15.5 region are observed; and their effects depend on the localization, size,
and the parental mode of transmission. We report a novel IGF2/H19 domain cis
triplication in the 11p15.5 region identified in a girl with BWS and her father
with symptoms of SRS. To the best of our knowledge, this is the first report of
IGF2/H19 domain triplication associated with BWS or SRS and the second report of
an additional copy of this region in an individual with clinical features of SRS.
This study shows that paternal IGF2/H19 domain triplication results in BWS, gives
additional support to the hypothesis that the maternal amplification of IGF2/H19
domain may lead to the manifestation of SRS and underlines difficulties of
genetic counseling in patients with CNVs involving the 11p15.5 region. (c) 2016
Wiley Periodicals, Inc.
PMID- 27612311
TI - [Functional Electrical Stimulation in a Case of Drop Foot and Atactic Gait:
Expert Assessment of Contested Medical Aids].
AB - Expert medical opinions are necessary in pretrial cases and other legal matters.
They act as means of evidence for administrative bodies and courts. It may be
necessary to adapt the method of evaluation depending upon the issue or subject
matter to be evaluated. We report on a social court case, which needed to answer
the question of the medical necessity of a functional electrical stimulation
orthosis prescribed to improve the function of a drop foot accompanied by an
atactic gait disorder. The claimant suffered from a stroke, which had occurred
several years before. Her aids were an ankle-foot-orthosis for foot lift and a
wheeled walker. The current treatment was to be augmented by the disputed device.
The statutory health insurance declined to meet the costs. They failed to find
relevant benefits after analysis of video tapes of the patient's gait while using
an electrical stimulation orthosis. The social court requested an expert opinion
to answer the question as to whether or not there was a relevant functional
benefit to using functional electrical stimulation over the existing orthosis or
to an alternative treatment. Video documentation was desired by the court. We
used the clinic's gait analysis laboratory, which is equipped with a gait course
and the claimed video documentation. Standardised video documentation offers
substantial advantages for answering forensic questions such as these. It assures
reproducibility and comparability of all tested scenarios, with objectification
of the individual advantages or limitations. This gain in both validity and
reliability fulfills the scientific requirements placed upon an expert
assessment.
PMID- 27612310
TI - Comparison between group and personal rehabilitation for dementia in a geriatric
health service facility: single-blinded randomized controlled study.
AB - AIM: The aim of this study was to compare the effects of rehabilitation involving
group and personal sessions on demented participants. METHODS: This single
blinded randomized controlled trial included 60 elderly participants with
dementia in a geriatric health service facility, or R oken. Staff members, who
did not participate in the intervention, examined cognitive function, mood,
communication ability, severity of dementia, objective quality of life, vitality,
and daily behaviour. After a baseline assessment, participants were randomly
divided into three groups: (i) group intervention; (ii) personal intervention;
and (iii) control. The 1-h group intervention (3-5 subjects) and 20-min personal
intervention (one staff member per participant) were performed twice a week for
12 weeks (24 total sessions). The cognitive rehabilitation programme consisted of
reminiscence, reality orientation, and physical exercise, and it was based on
five principles of brain-activating rehabilitation; (i) pleasant atmosphere; (ii)
communication; (iii) social roles; (iv) praising; and (v) errorless support. Data
were analyzed after the second assessment. RESULTS: Outcome measures were
analyzed in 43 participants-14 in the control group, 13 in group intervention,
and 16 in personal intervention. Repeated measure ancova showed a significant
interaction for cognitive function score (Mini-Mental State Examination) between
group intervention and controls ( F = 5.535, P = 0.029). In the post-hoc
analysis, group intervention showed significant improvement (P = 0.016). Global
severity of dementia tended to improve (P = 0.094) in group intervention compared
to control (Mann-Whitney U -test). There were no significant interactions or
improvements for other measurements. CONCLUSIONS: Group rehabilitation for
dementia is more effective for improving cognitive function and global severity
of dementia than personal rehabilitation in Roken.
PMID- 27612312
TI - [Validity and Reliability of the German Version of the HSS Expectation
Questionnaire on Hip Joint Replacement].
AB - Background: Total hip arthroplasty is one of the most successful operations in
medicine. The clinical result after surgery and compliance during rehabilitation
are influenced by the patient's expectations. There is a lack of a validated
German instrument to record these expectations in a standardised manner.
Patients: 193 patients from the Dresden Hip Register with osteoarthritis of the
hip were surveyed with respect to their expectations before the operation. The
study sample consists of 108 women and 85 men. The average age of the patients
was 59.7 years, with a standard deviation of 12.2 years. Methods: The Hospital
for Special Patient Expectations Survey was translated into German and culturally
adapted. In addition, the RKI demographic core data set, the HADS-D, LOT-R and
the SCL-(K-)9 were collected to validate the instrument. In the statistical
analysis, four main factors could be distinguished. These were "everyday
activities", "pain relief and improvement in function", "medication and social
participation" and "gait improvement". Results: Patients were predominantly
married. 20 % of the women were widowed. 20 % had received higher education.
Almost half of the patients were retired, 30 % were employed, 15.1 % self
employed and 7.3 % were unemployed. For most of the items, patients expected
major improvements up to normalisation of their health. There were many different
answers to several items, such as the question on occupation. For sporting and
sexual activities no high expectations were given. The average expectation of the
whole sample shows major differences to individual expectations. Men showed
higher expectations for medication, social participation and gait improvement
than did women. There were lower expectations for everyday activities, medication
and social participation and gait improvement for older patients. Summary: The
German version of the HSS patients expectation survey was validated. The
instrument is useful in the preoperative setting to give the surgeon a first
impression on the patient's expectations.
PMID- 27612313
TI - [Is it Possible to Arouse Interest in a Career in Traumatology with a Curricular
Course in Medical School?]
AB - Background: There is a serious lack of young doctors in trauma surgery, which has
intensified in recent years. The reasons are complex. Studies have shown that the
interest in starting a career in surgery significantly decreases during medical
school. To counteract the lack of young talent in the clinic, interest in the
subject should be aroused in medical school. The aim of the present study was to
evaluate current teaching at our university, where trauma surgery is a curricular
subject with mandatory attendance for all medical students. Material and Methods:
The current curriculum is intended for medicine students in their fifth year. The
curriculum comprises lectures, practical courses and observation modules held in
small groups. Students are provided with an experienced surgeon as teacher and
mentor for the whole week. A teaching and training centre is available for the
practical courses. In an anonymised questionnaire, students were asked about
their overall assessment and the training success of practical and theory
oriented modules, as well as their specific interest in traumatology. Results:
The evaluated curriculum gave very good results, with an overall rating of 1.53
(average) on a 6-point Likert scale in the overall assessment. It could be shown
that students previously not interested in starting a career in trauma surgery
showed significantly more interest in the subject after the curriculum. The
practical parts scored best in the individual assessment. Conclusion: We showed
that intensive teaching can arouse interest in traumatology in students who had
been indifferent to orthopaedics and traumatology.
PMID- 27612314
TI - [Effects of a Pelvic Ring Injury on Earning Capacity].
AB - Introduction: Pelvic ring injuries occur in 3-8 % of patients with fractures.
They are rare, with an annual incidence of only 19-37 per 100,000 people
annually. There have been publications on the generation of these injuries, as
well as their diagnosis and treatment concepts, but there is little information
on how these injuries impact the ability to work. Patients: The study covered all
hospitalised patients between January 2003 and December 2011 with a pelvic ring
injury, who had already been included in the data collection of the AG Becken III
and who had had a work-related accident. Data acquisition was completed 12 months
after the first cover letter. Data collection was supported by the statutory
accident insurance institutions. Responses to the following questions were
collected: Results: During the time period, 835 patients were admitted to our
hospital with an injury to the pelvic ring or acetabulum. 632 patients (75.7 %)
had a pelvic ring injury. 95 patients had a work-related accident, for which 67
records (70.5 %) could be evaluated. Seven patients were in retirement at the
time. The average age was 48 years. In the patient population, we identified 9
type A, 16 type B and 42 type C injuries. The mean duration of incapacity for
work was 9.5 months. 36 patients were able to return to their old work again, 22
patients did not. For two of these patients, this was due to cerebral
haemorrhage. The mean reduction in earning capacity at the 1st and 2nd pension
reports was 28 %. The individual rating of the degree of trauma lay between 0 %
(B2.1) to 60 % (C1.2). Subgroup analysis was not performed, due to the small
number of patients and their lack of homogeneity. As only hospitalised patients
were included in the study group, there was excessive accumulation of pelvic B
and C fractures in the patient group. The study shows that pelvic ring injuries
can have a significant impact on the duration of the incapacity and the ability
to work.
PMID- 27612315
TI - [Large Hibernoma of the Proximal Upper Arm and the Axilla - Literature Review and
Case Description of a Very Rare Benign Soft Tissue Tumor].
AB - Hibernomas are very rare benign soft tissue tumors arising from brown fat.
Malignant transformation or metastases are unknown. Males seems to be affected
more often. Most patients are aged 20 to 40, but patients with intraosseous
hibernomas are older. In children, hibernomas are extremely rare. The tumors grow
slowly and have usually been present for a few years on presentation. Hibernomas
are typically located on the thigh, neck, axilla or in the peri- und
interscapular region. Diagnostic work-up in symptomatic hibernomas usually
includes conventional X-ray and magnetic resonance tomography (MRI) with contrast
medium. Asymptomatic hibernomas are often found accidentally in the diagnostic
work-up of other diseases. Important differential diagnoses are lipomas, well
differentiated liposarcomas, rhabdomyomas, granular cell tumors and sebeceous
adenomas. Incisional biopsy should be performed to allow definitive histological
diagnosis before definitive therapy. According to the literature, histologically
preserved hibernomas can be removed with curative intention and marginal
resection. After complete tumor removal, local recurrence has not been described.
The following article describes the case of a large hibernoma of the proximal
arm, involving the axilla, and describes the epidemiology, clinical behavior,
diagnostic work-up, therapy and prognosis of this very rare benign fatty soft
tissue tumor, on the basis of a review of current literature.
PMID- 27612316
TI - [Consequences of the Foundation of a University Centre for Orthopaedics and
Accident Surgery].
AB - Background: Since the combination of orthopaedic and traumatology surgery as a
single speciality, an extremely wide variety of orthopaedic and trauma surgery
centres have been founded in Germany. The present investigation analysed the
degree to which additional value has been generated by merging two previously
independent university departments - one for orthopaedics, the other for trauma
surgery - into a single orthopaedics and trauma surgery centre. Material and
Methods: The centre, merged in 1 June 2013, is led by two equal co-chairs (a full
professor for orthopaedics and a full professor for trauma surgery). It consists
of an acute division and five other divisions for specific parts of the body. The
pre-existing certifications (level 1 trauma- and joint arthroplasty centre) were
maintained in the new merged entity. Data from patient and employee
questionnaires, as well as key economic indicators, were compared before and
after the merger. Results: 11 % of the patients rated the medical treatment as
mediocre or bad before the merger. After the merger, 5.7 % of the patients were
moderately satisfied or unsatisfied; 92 % would recommend the merged centre to
others and would return for further treatment. The evaluation of patient
complaints before and after the merger showed no change. The evaluation of the
employee questionnaires showed heterogeneous results. Overall, positive
evaluations predominated, but in areas where there had been major changes,
negative aspects were occasionally reported. The merger did not bring about any
essential change in the number of in-patients (2012: 6693; 2014: 6649) or in the
severity of the medical cases (CMI in 2012: 1.41; in 2014: 1.45). But in 2015,
there was an increase in the number of in-patients (6837) and in the CMI (1.54).
In the out-patient clinic, the merger led to a reduction in the material costs
per patient (2012: 3.53 ?/patient; 2014: 3.07 ?/patient) and in the staff costs.
The material costs for the entire centre were also reduced by 14 %. Conclusion:
By merging the university orthopaedic and trauma surgery centres,
transdisciplinary and transdepartmental improvements in patient care were
achieved for musculoskeletal illnesses and injuries, and a sustainable structure
was established for the advanced training for the joint specialist title of
orthopaedics and trauma surgery. The merger also led to additional economic
synergies, with a mid-term potential for increases in the number of patients and
in CMI. To improve or at least maintain the level of employee satisfaction, staff
must be actively included in the process.
PMID- 27612317
TI - Cardiovascular safety trials of incretin-based drugs: What do they mean?
AB - Incretin-based dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1
receptor agonists are newer choices of antidiabetic medications that are now most
widely used worldwide. Preclinical study results suggest that the two drugs
potentially exert benefits to prevent onsets and/or progressions of diabetes
related complications, such as myocardial infarctions and strokes. Outcomes of
five clinical trials to evaluate the cardiovascular (CV) safety of dipeptidyl
peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonist have been
recently reported. The heart failure findings of the Saxagliptin Assessment of
Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in
Myocardial Infarction 53 (SAVOR-TIMI53) are unexpected and very concerning;
results of the Examination of Cardiovascular Outcomes with Alogliptin vs Standard
of Care (EXAMINE), the Trial Evaluating Cardiovascular Outcomes with Sitagliptin
(TECOS) and the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA)
encourage neutral CV safety profiles of incretin-based drugs in individuals with
type 2 diabetes and established CV diseases or multiple CV risks. Furthermore,
the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular
Outcome Results (LEADER) results show the benefits of liraglutide in preventing
CV events in a similar study population. Despite the many preclinical studies
showing the beneficial effects of incretin-related drugs, most CV safety trials
of incretin-based drugs, except for LEADER, did not show benefits for CV events.
It is important to recognize that CV safety trials were carried out to meet the
US Food and Drug Administration guidance to assess CV safety of all new
antidiabetic drugs; they were not designed to assess their benefits for CV
events. Therefore, the long-term potential benefit, as well as even the safety,
of incretin-based drugs for certain CV outcomes has not been definitively
established, and requires evaluation in more specific and more relevant trials.
If the need for CV safety trials would be determined based on an individual
drug's safety data during its earlier development as well as its mechanism of
action, resources could be saved for carrying out such clinical trials.
PMID- 27612318
TI - Emerging roles and context of circular RNAs.
AB - Circular RNAs (circRNAs) represent a large class of noncoding RNAs (ncRNAs) that
have recently emerged as regulators of gene expression. They have been shown to
suppress microRNAs, thereby increasing the translation and stability of the
targets of such microRNAs. In this review, we discuss the emerging functions of
circRNAs, including RNA transcription, splicing, turnover, and translation. We
also discuss other possible facets of circRNAs that can influence their function
depending on the cell context, such as circRNA abundance, subcellular
localization, interacting partners (RNA, DNA, and proteins), dynamic changes in
interactions following stimulation, and potential circRNA translation. The
ensuing changes in gene expression patterns elicited by circRNAs are proposed to
drive key cellular processes, such as cell proliferation, differentiation, and
survival, that govern health and disease. WIREs RNA 2017, 8:e1386. doi:
10.1002/wrna.1386 For further resources related to this article, please visit the
WIREs website.
PMID- 27612319
TI - Pregnancy outcomes in myeloproliferative neoplasms: UK prospective cohort study.
AB - The reported higher risk of maternal and fetal complications in women with
myeloproliferative neoplasms (MPN) poses challenge during pregnancy. A national
prospective study of maternal and fetal outcomes of pregnant women with a
diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance
System between January 2010 and December 2012. Fifty-eight women with a diagnosis
of MPN were identified; 47 (81%) essential thrombocythaemia, five (9%)
polycythaemia vera, five (9%) myelofibrosis and one (2%) MPN-unclassified. There
were 58 live births. The incidence of miscarriage was 1.7/100 (95% confidence
interval [CI]: 0.04-9.24) and the perinatal mortality rate was 17/1000 (95% CI:
0.44-92.36) live and stillbirths. Incidence of maternal complications was 9%
(5/57) pre-eclampsia, 9% (5/57) post-partum haemorrhage and 3.5% (2/57) post
partum haematoma. There were no maternal deaths or thrombotic events. Delivery
was induced in 45% (24/53) of women and the Caesarean section rate was 45%
(24/53). The majority (85%, 45/53) delivered at term (>37 weeks gestation).
Twenty-two percent (12/54) of neonates were below the 10% centile for growth and
13% (7/54) required admission to a neonatal care-unit; there were no neonatal
deaths. The findings of this large, UK prospective study suggests women with MPN
appear to have successful pregnancies with better outcomes than would be
anticipated from the literature.
PMID- 27612320
TI - Modern management of phagocyte defects.
AB - Phagocytic neutrophil granulocytes are among the first immune cells active at
sites of infection, forming an important first-line defense against invading
microorganisms. Congenital immune defects concerning these phagocytes may be due
to reduced neutrophil numbers or function. Management of affected patients
depends on the type and severity of disease. Here, we provide an overview of
causes and treatment of diseases associated with congenital neutropenia, as well
as defects of the phagocytic respiratory burst.
PMID- 27612321
TI - Fixed drug eruption due to three antihistamines of a same chemical family:
Cetirizine, levocetirizine, and hydroxyzine.
PMID- 27612322
TI - Molecular determination of the clonal relationships between multiple tumors in
BRCA1/2-associated breast and/or ovarian cancer patients is clinically relevant.
AB - Female BRCA1/2 mutation carriers affected with breast and/or ovarian cancer may
develop new tumor deposits over time. It is of utmost importance to know the
clonal relationships between multiple tumor localizations, enabling
differentiation between multiple primaries or metastatic disease with
consequences for therapy and prognosis. We evaluated the value of targeted next
generation sequencing in the diagnostic workup of BRCA1/2 mutation carriers with
>=2 tumor localizations and uncertain tumor origins. Forty-two female BRCA1/2
mutation carriers with >=2 tumor localizations were selected. Patients with
inconclusive tumor origin after histopathological revision were 'cases'; patients
with certain tumor origin of >=3 tumors served as 'controls'. Tumors of cases and
controls were analyzed by targeted next generation sequencing using a panel
including CDKN2A, PTEN and TP53, hotspot mutation sites for 27 different genes
and 143 single nucleotide polymorphisms for detection of loss of heterozygosity.
Based on prevalence of identical or different mutations and/or loss of
heterozygosity patterns, tumors were classified as 'multiple primaries' or 'one
entity'. Conventional histopathology yielded a conclusive result in 38/42 (90%)
of patients. Four cases and 10 controls were analyzed by next generation
sequencing. In 44 tumor samples, 48 mutations were found; 39 (81%) concerned TP53
mutations. In all 4 cases, the intra-patient clonal relationships between the
tumor localizations could be unequivocally identified by molecular analysis. In
all controls, molecular outcomes matched the conventional histopathological
results. In most BRCA1/2 mutation carriers with multiple tumors routine pathology
work-up is sufficient to determine tumor origins and relatedness. In case of
inconclusive conventional pathology results, molecular analyses using next
generation sequencing can reliably determine clonal relationships between tumors,
enabling optimal treatment of individual patients.
PMID- 27612323
TI - Microleakage around Class V Composite Restorations after Ultrasonic Scaling and
Sonic Toothbrushing around their Margin.
AB - OBJECTIVES: To measure microleakage around class V composite restorations after
piezoelectric ultrasonic scaling and sonic toothbrushing. METHODS: 3 mm * 2 mm *
1.5 mm boxes were prepared on buccal and lingual surfaces of extracted molars
centered on the cementum-enamel junction. Half the preparations were beveled (0.5
mm). Preparations were restored with composite and polished. Restorations on one
side of the teeth were either traced with an ultrasonic scaler (60 seconds, n =
16) or brushed in a sonic toothbrushing machine (2 hours, n = 16). After
thermocycling (10,000 cycles/5-55 degrees C), specimens were immersed in 5 wt%
Fuchsine solution (24 hours). Samples were sectioned and evaluated for percentage
of dye penetration. Data were analyzed with an exact Wilcoxon rank-sum test and
exact Wilcoxon signed-rank test (alpha = 0.05). RESULTS: Microleakage was
observed at the cementum-composite interface but not the enamel-composite
interface. There was not a statistically significant effect of the bevel for
ultrasonic scaling or for sonic toothbrushing. Data obtained with and without a
bevel were combined and a statistically significant difference in microleakage
between the treatment and control sides of the tooth were found for ultrasonic
scaling (32.5%+/-44.9%, n = 16; p = 0.016) but not sonic toothbrushing (2.5% +/-
41.2%, n = 16; p = 1.0). CONCLUSIONS: Piezoelectric ultrasonic scaling increased
microleakage at cementum-composite interface and there was no difference in
microleakage with the use of a bevel. CLINICAL SIGNIFICANCE: Piezoelectric sonic
scaling around Class V composite restorations with margins in cementum should be
avoided. Beveled margins will not reduce the incidence of microleakge resulting
from ultrasonic scaling in Class V restorations. Placing the apical margin of the
restoration in enamel should be attempted whenever possible to prevent future
microleakage. (J Esthet Restor Dent 29:41-48, 2017).
PMID- 27612325
TI - Proteomic and network analysis of pregnancy-induced changes in the porcine
endometrium on Day 12 of gestation.
AB - Conceptus attachment is a time-sensitive process that requires a synchronized
uterine environment created by molecular changes in the endometrium in response
to ovarian hormones and conceptus signals. Porcine conceptuses undergo rapid
elongation and differentiation, and secrete estrogens that serve as maternal
recognition-of-pregnancy signals during the peri-implantation period (Days 11
12). Pregnancy-induced proteomic changes in the porcine endometrium were measured
during this period using two-dimensional differential gel electrophoresis of
endometrial protein lysates from Day-12 pregnant versus non-pregnant animals (n =
4 each). Forty-four differentially abundant proteins in the pregnant endometrium
were identified by mass spectrometry. The pregnant endometrium was associated
with a unique protein profile, revealed by principal component analysis. A
pregnancy-dependent increase in the abundance of serpins, cofilin, annexin A2,
aldose reductase, cyclophilin, protein disulphide isomerase A3, and peroxiredoxin
1 was observed. Western blotting for some of the selected proteins confirmed
their enrichment during pregnancy. Ingenuity pathway analysis identified several
functions specifically over-represented among the differentially abundant
proteins in the pregnant endometrium, including calcium signaling, angiogenesis,
leukocyte migration, and cell movement. Interleukin-1 beta and beta-estradiol
were identified as upstream regulators of several high-abundance proteins from
pregnancy. Therefore, signals from porcine conceptuses, such as estrogens,
interleukin 1B, and epidermal growth factor, either alone or in coordination with
other factors, prepare the uterus for implantation. Mol. Reprod. Dev. 83: 827
841, 2016 (c) 2016 Wiley Periodicals, Inc.
PMID- 27612324
TI - The Power of Place: Social Network Characteristics, Perceived Neighborhood
Features, and Psychological Distress Among African Americans in the Historic Hill
District in Pittsburgh, Pennsylvania.
AB - African American neighborhoods have been historically targeted for urban renewal
projects, which impact social composition and resident's health. The Hill
District in Pittsburgh, PA is such a neighborhood. This research sought to
investigate the extent to which social networks and perceived neighborhood social
cohesion and safety were associated with psychological distress among residents
in an African American neighborhood undergoing urban renewal, before the
implementation of major neighborhood changes. Findings revealed a modest,
significant inverse association between social network size and psychological
distress (beta = -0.006, p < .01), even after controlling for age, employment,
education, and income. Perceived neighborhood safety predicted decreased
psychological distress (beta = -1.438, p < .01), but not social cohesion, which
is consistent with past research. Findings suggest that social networks protect
against psychological distress, but neighborhood perceptions are also paramount.
PMID- 27612326
TI - Press-pulse interactions: effects of warming, N deposition, altered winter
precipitation, and fire on desert grassland community structure and dynamics.
AB - Global environmental change is altering temperature, precipitation patterns,
resource availability, and disturbance regimes. Theory predicts that ecological
presses will interact with pulse events to alter ecosystem structure and
function. In 2006, we established a long-term, multifactor global change
experiment to determine the interactive effects of nighttime warming, increased
atmospheric nitrogen (N) deposition, and increased winter precipitation on plant
community structure and aboveground net primary production (ANPP) in a northern
Chihuahuan Desert grassland. In 2009, a lightning-caused wildfire burned through
the experiment. Here, we report on the interactive effects of these global change
drivers on pre- and postfire grassland community structure and ANPP. Our
nighttime warming treatment increased winter nighttime air temperatures by an
average of 1.1 degrees C and summer nighttime air temperature by 1.5 degrees C.
Soil N availability was 2.5 times higher in fertilized compared with control
plots. Average soil volumetric water content (VWC) in winter was slightly but
significantly higher (13.0% vs. 11.0%) in plots receiving added winter rain
relative to controls, and VWC was slightly higher in warmed (14.5%) compared with
control (13.5%) plots during the growing season even though surface soil
temperatures were significantly higher in warmed plots. Despite these significant
treatment effects, ANPP and plant community structure were highly resistant to
these global change drivers prior to the fire. Burning reduced the cover of the
dominant grasses by more than 75%. Following the fire, forb species richness and
biomass increased significantly, particularly in warmed, fertilized plots that
received additional winter precipitation. Thus, although unburned grassland
showed little initial response to multiple ecological presses, our results
demonstrate how a single pulse disturbance can interact with chronic alterations
in resource availability to increase ecosystem sensitivity to multiple drivers of
global environmental change.
PMID- 27612327
TI - Allergic rhinitis causes loss of smell in children: The OLFAPEDRIAL study.
AB - BACKGROUND: The objective of the OLFAPEDRIAL study was to assess the olfactory
dysfunction in allergic paediatric population, which has been scarcely studied.
METHODS: Observational, cross-sectional and multicentre study evaluated the sense
of smell in untreated allergic rhinitis (AR) paediatric patients aged 6-12 years.
RESULTS: Forty-four per cent (551 of 1260) of children with AR reported smell
dysfunction, with both loss of smell frequency (52.1%, p < 0.001) and intensity
(0.75 +/- 0.84, p < 0.0001) being more frequent in patients with persistent than
intermittent AR (38.0% and 0.51 +/- 0.73, respectively). In addition, both loss
of smell frequency and intensity increased according to disease severity (m-ARIA
classification) but always being significantly higher in persistent (p < 0.0001)
than in intermittent AR. CONCLUSIONS: Children with allergic rhinitis present a
mild-moderate loss of smell frequency and intensity which is clearly related to
the disease duration and severity. The loss of smell can be considered, as in
adults, a clinical marker of disease severity.
PMID- 27612328
TI - Diagnostic accuracy of the use of parental-reported sleep bruxism in a
polysomnographic study in children.
AB - BACKGROUND: Polysomnography (PSG) is the gold standard for sleep bruxism (SB)
diagnosis. PSG/SB children's criteria are not available; thus, parental-report SB
is widely used. AIM: Assessing the diagnostic accuracy of parental report of
sleep tooth grinding (STG) with a PSG/SB diagnosis in children, adopting adult
criteria. DESIGN: Thirty-seven children from clinics of Universidad CES were
included. Parents filled the Children's Sleep Habits Questionnaire (CSHQ)
assessing the single-observation report - CSHQ - of STG with a No/Yes answer and
five ordinal answers. A 5-day diary reporting the presence/absence of STG
(multiple-observation report) was also completed. Each child underwent a single
night PSG study. Sensitivity, specificity, positive predictive value, negative
predictive value, accuracy, likelihood ratios, Spearman correlation coefficient,
and Cohen's kappa coefficient were used to analyze data. RESULTS: Single
observation, using No/Yes answer, showed acceptable specificity and NPV, while
low PPV and sensitivity. Accuracy and likelihood ratios were low. When using the
five ordinal answers, weak correlation and fair agreement (r = 0.34 and kappa =
0.40) with PSG/SB adult criteria were found. Multiple-observation evaluation of
STG presented moderate correlation and agreement (r = 0.50 and kappa = 0.48).
CONCLUSIONS: Although multiple-observation report achieved better agreement than
single-observation report, our results failed supporting the validity of report
strategies for the diagnosis of SB in children, as an equivalent of PSG/SB adult
criteria.
PMID- 27612329
TI - [Malignant Pleural Mesotheliomas].
AB - Malignant pleural mesotheliomas (MPM) are very aggressive tumors, which originate
from the mesothelial cells of the pleural surface. The main risk factor
associated with MPM is exposure to asbestos. The latency period between asbestos
exposure and MPM can be 30-60 years. Clinical symptoms and signs are often
nonspecifc. The diagnosis of MPM requires an adequate tissue specimen for
pathological examination, and video assisted thoracoscopic surgey (VATS) is
associated with the highest diagnostic yield. MPM are histologically classified
into epitheloid, sacromatoid and biphasic (mixed) sub-types. Accurate staging
with invasive tests, if needed, is an important step before an interdisciplinary
team can decide on an optimal (multi-modal) treatment approach. A multi-modal
treatment approach (surgery, radiation oncology and chemotherapy) is superior to
all approaches relying only on a single modality, if the patient qualifies for it
from an oncological and functional standpoint. The goal of the surgical therapy
is to achieve macroscopic complete resection. There are two competing surgical
approaches and philosophies: extrapleural pneumonectomy (EPP) and radical
pleurectomy (RP). Over the last years a paradigm shift from EPP to RP occurred
and RP is now often the preferred surgical option.
PMID- 27612330
TI - Materials and methods for higher performance screen-printed flexible MRI receive
coils.
AB - PURPOSE: To develop methods for characterizing materials used in screen-printed
MRI coils and improve signal-to-noise ratio (SNR) with new lower-loss materials.
METHODS: An experimental apparatus was created to characterize dielectric
properties of plastic substrates used in receive coils. Coils were fabricated by
screen printing conductive ink onto several plastic substrates. Unloaded and
sample loaded quality factor (QUnloaded /QLoaded ) measurements and scans on a 3T
scanner were used to characterize coil performance. An experimental method was
developed to describe the relationship between a coil's QUnloaded and the SNR it
provides in images of a phantom. In addition, 3T scans of a phantom and the head
of a volunteer were obtained with a proof-of-concept printed eight-channel array,
and the results were compared with a commercial 12-channel array. RESULTS:
Printed coils with optimized substrates exhibited up to 97% of the image SNR when
compared with a traditional coil on a loading phantom. QUnloaded and the SNR of
coils were successfully correlated. The printed array resulted in images
comparable to the quality given by the commercial array. CONCLUSION: Using the
proposed methods and materials, the SNR of printed coils approached that of
commercial coils while using a new fabrication technique that provided more
flexibility and close contact with the patient's body. Magn Reson Med 78:775-783,
2017. (c) 2016 International Society for Magnetic Resonance in Medicine.
PMID- 27612331
TI - Age-related heterogeneity of Burkitt lymphoma: response to Mbulaiteye and
Anderson.
PMID- 27612333
TI - U.S. Health in International Perspective: Shorter Lives, Poorer Health.
PMID- 27612332
TI - Two-Dimensional Crowding Uncovers a Hidden Conformation of alpha-Synuclein.
AB - The intrinsically disordered protein (IDP), alpha-synuclein (alphaS), is well
known for phospholipid membrane binding-coupled folding into tunable helical
conformers. Here, using single-molecule experiments in conjunction with ensemble
assays and a theoretical model, we present a unique case demonstrating that the
interaction-folding landscape of alphaS can be tuned by two-dimensional (2D)
crowding through simultaneous binding of a second protein on the bilayer surface.
Unexpectedly, the experimental data show a clear deviation from a simple
competitive inhibition model, but are consistent with a bimodal inhibition
mechanism wherein membrane binding of a second protein (a membrane interacting
chaperone, Hsp27, in this case) differentially inhibits two distinct modules of
alphaS-membrane interaction. As a consequence, alphaS molecules are forced to
access a hidden conformational state on the phospholipid bilayer in which only
the higher-affinity module remains membrane-bound. Our results demonstrate that
macromolecular crowding in two dimensions can play a significant role in shaping
the conformational landscape of membrane-binding IDPs with multiple binding
modes.
PMID- 27612334
TI - Healing the Wounds After the Fight: Army Medical Care to Repatriated Captives,
Part III.
PMID- 27612335
TI - Asthmatic Woman With Shortness of Breath.
PMID- 27612336
TI - "China 1 USA 0": A Former Ebola Provider's Explanation Why the United States is
Falling Behind in the Global Health Arena.
PMID- 27612337
TI - Exercise and Post-Traumatic Stress Disorder in Military Veterans: A Systematic
Review.
AB - Post-traumatic stress disorder (PTSD) is a prominent mental health issue for many
military veterans. Recent evidence from nonveteran populations with PTSD suggests
that exercise may be a potential treatment option. As such, the purpose of this
review was to (1) provide the rationale for the use of exercise in the treatment
of veterans with PTSD and (2) systematically review studies examining the
relationship between exercise and PTSD in military veterans. A search of
electronic databases (PubMed, PsycINFO, and Web of Science) for relevant studies
published in print or online from January 1980 to September 2015 produced 204
unique articles and 13 relevant studies (9 observational studies, 2 experimental,
and 2 qualitative). Results of these initial studies are promising and suggest
that regular exercise is inversely correlated with PTSD and its symptoms in
military veterans. However, the longitudinal effect of exercise on PTSD in
military veterans remains unclear because the current research lacks a common
focus and suffers from several methodological limitations. Recommendations for
the development of future trials are included.
PMID- 27612338
TI - The Emerging Role of Mindfulness Meditation as Effective Self-Management
Strategy, Part 1: Clinical Implications for Depression, Post-Traumatic Stress
Disorder, and Anxiety.
AB - Mindfulness-based interventions (MBIs) have been increasingly utilized in the
management of mental health conditions. This first review of a two-part series
evaluates the efficacy, mechanism, and safety of mindfulness meditation for
mental health conditions frequently seen after return from deployment. Standard
databases were searched until August 4, 2015. 52 systematic reviews and
randomized clinical trials were included. The Strength of Recommendation (SOR)
Taxonomy was used to assess the quality of individual studies and to rate the
strength of evidence for each clinical condition. Adjunctive mindfulness-based
cognitive therapy is effective for decreasing symptom severity during current
depressive episode, and for reducing relapse rate in recovered patients during
maintenance phase of depression management (SOR moderate [SOR B]). Adjunctive
mindfulness-based stress reduction is effective for improving symptoms, mental
health-related quality of life, and mindfulness in veterans with combat post
traumatic stress disorder (PTSD) (SOR B). Currently, there is no sufficient data
to recommend MBIs for generalized anxiety disorder (SOR B). MBIs are safe,
portable, cost-effective, and can be recommended as an adjunct to standard care
or self-management strategy for major depressive disorder and PTSD. Future large,
well-designed randomized clinical trials in service members and veterans can help
plan for the anticipated increase in demand for behavioral health services.
PMID- 27612339
TI - The Emerging Role of Mindfulness Meditation as Effective Self-Management
Strategy, Part 2: Clinical Implications for Chronic Pain, Substance Misuse, and
Insomnia.
AB - Mindfulness-based interventions have been increasingly utilized in the management
of chronic pain since 1982. This second review of a two-part series evaluates the
efficacy, mechanism, and safety of mindfulness meditation for chronic pain,
substance use disorder, tobacco use disorder, and insomnia frequently co
occurring after return from deployment. Standard databases were searched until
August 4, 2015. 72 relevant systematic reviews and clinical trials met the
inclusion criteria. The Strength of Recommendation Taxonomy was used to assess
the quality of individual studies and to rate the strength of recommendation
(SOR) for each clinical condition. Mindfulness-based interventions effectively
and durably reduce pain intensity, improve functional status, pain-related
psychological consequences, quality of life (SOR B). They can also be utilized as
an adjunctive intervention aimed at improving health-related quality of life in
individuals with substance use disorders interested in self-management strategies
(SOR B). Mindfulness training for smokers used adjunctively with pharmacotherapy
shows efficacy in maintaining abstinence comparable to that of the current
standard of care (SOR B). Future large, well-designed randomized clinical trials
using active controls in service members and veterans with co-occurring pain and
psychological health conditions are necessary to provide more precise clinical
guidance.
PMID- 27612341
TI - Mindfulness-Based Stress Reduction for Military Women With Chronic Pelvic Pain: A
Feasibility Study.
AB - INTRODUCTION: One of the most common reasons women seek gynecologic health care
services is for chronic pelvic pain (CPP) and women in the military are no
exception. For women diagnosed with CPP, the burden can be difficult as they
struggle to perform military obligations. A chronic low-grade systemic disease
believed triggered by inflammation, CPP is difficult to diagnose and treat. With
limited treatment strategies available, this study sought to examine the
feasibility of implementing a mindfulness-based stress reduction (MBSR) program
in a military population. METHODS: This prospective study evaluated the
feasibility of a standard 8-week MBSR training program in a population of active
duty women previously diagnosed with CPP (N = 15). Participants also completed
the Kentucky Inventory of Mindfulness survey and the Brief Pain Inventory, did
home practice and kept a daily diary. Vaginal swabs were obtained at baseline and
at study completion. CONCLUSIONS: A standard MBSR program is difficult to
implement in a military population; other delivery formats should be considered.
There was a trend suggestive that program participation promotes mindfulness,
reduces pain, and promotes modulation of select pro-inflammatory cytokines. On
the basis of results of this pilot feasibility study, further research is
warranted.
PMID- 27612340
TI - Listening to the Patient: Women Veterans' Insights About Health Care Needs,
Access, and Quality in Rural Areas.
AB - OBJECTIVES: Many work to ensure that women veterans receive appropriate and
timely health care, yet the needs of those living in rural areas are often
ignored. This is a critical oversight given the multitude of reports documenting
rural access problems and health disparities. Lacking this, we are unable to plan
for and evaluate appropriate care for this specific group. In this project, we
spoke with rural women veterans to document service needs and quality of care
from their perspective. METHODS: Rural women veterans' views about health care
access and quality were ascertained in a series of five, semistructured focus
groups (n = 35) and completion of a demographic questionnaire. Content analysis
documented focus-group themes. RESULTS: Participants said that local dental,
mental health, and gender-specific care options were needed, as well as
alternative healing options. Community-based support for women veterans and
interaction with female peers were absent. Participants' support for telehealth
was mixed, as were requests for gender-specific care. Personal experiences in the
military impacted participants' current service utilization. CONCLUSIONS: Action
by both Veterans Affairs and the local community is vital to improving the health
of women veterans. Service planning should consider additional Veterans Affairs
contracts, mobile health vans, peer support, and enhanced outreach.
PMID- 27612342
TI - Using a Mobile Application in the Management of Anger Problems Among Veterans: A
Pilot Study.
AB - OBJECTIVE: This feasibility pilot study evaluated the usability of a mobile
application (app), Remote Exercises for Learning Anger and Excitation Management
(RELAX), as an adjunct to an anger management treatment delivered to Veterans.
METHODS: Four Veterans completed pre- and post-treatment measures of anger, post
traumatic stress disorder, depression, interpersonal functioning, and app use.
RESULTS: Descriptive results of clinical outcomes are provided. Qualitative data
included Veterans' and therapists' feedback regarding the acceptability of the
technology, satisfaction with the RELAX app, homework facilitation, and
suggestions for improvement. Large reductions in anger, post-traumatic stress
disorder and depression symptoms, and improvements in social functioning were
evidenced post-treatment. Veterans reported that the RELAX app was helpful and
appreciated its functionality. CONCLUSIONS: Our findings support using an app as
an adjunct to traditional anger management.
PMID- 27612343
TI - The Character Strengths of Special Forces Personnel: Insights for Civilian Health
Care Practitioners.
AB - Civilian employees, contractors, and private community clinicians are
increasingly providing health treatment to currently serving and former military
personnel. This study addresses recent calls for evidence-based information to
assist civilian practitioners in understanding the perspectives of their military
clients. To this end, the self-reported character strengths of military personnel
were elicited as an operationalized expression of their underlying personal
values that shape their perspectives and conduct as soldiers. Specifically,
Australian Army Special Forces operators and support personnel (N = 337) were
asked to rank themselves on 24 character strengths. The three character strengths
of integrity, teamworker, and good judgment were ranked significantly above
random assignment. Nearly all the respondents (84%) gave a top rank to at least
one of these character strengths. Differences between the operators and support
personnel were modest. Results are discussed with respect to establishing an
effective relationship between military clients and civilian health care
practitioners.
PMID- 27612344
TI - Rescaling the Post-Traumatic Stress Disorder Checklist for Use in Primary Care.
AB - The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) is a 17-item self-report
measure of PTSD symptom severity that has demonstrated excellent psychometric
properties across a variety of settings, purposes, and populations. The PCL is
widely used in busy Department of Defense primary care settings as part of
routine PTSD screening, requiring that it is easy for patients to complete and
providers to score. The clinical utility of the PCL may be improved through use
of a zero-anchored Likert-type response scale by providing intuitive anchors for
respondents and fewer calculations for clinic staff; however, changes to the
response scale may invalidate the known psychometric properties of the measure.
The purpose of this study is to evaluate the equivalence of a zero-anchored PCL
to the traditional one-anchored PCL. Differences in total scores were examined
using inferential confidence intervals. Substantial overlap of the inferential
confidence intervals and small Rg (maximum probable difference) value of 0.68
indicated that the zero-anchored PCL is equivalent to the one-anchored PCL on the
basis of our specified delta (amount of difference considered inconsequential).
These findings support the use of a zero-anchored PCL in clinical practice, and
more broadly, the use of zero-anchored measures in the larger field of
psychological assessment.
PMID- 27612345
TI - Relationship Between Body Fat and Physical Fitness in Army ROTC Cadets.
AB - The Army Physical Fitness Test (APFT), including timed push-ups, sit-ups, and
run, assesses physical performance for the Army. Percent body fat is estimated
using height and circumference measurements. The objectives of the study were to
(a) compare the accuracy of height and circumference measurements to other, more
accepted, body fat assessment methods and (b) determine the relationships between
body composition and APFT results. Participants included Reserve Officer Training
Corps (ROTC) cadets (n = 11 males, 2 females, 21.6 +/- 3.5 years) from a
midwestern university). At one visit, percent body fat was assessed using height
and circumference measurements, air-displacement plethysmography, and
bioelectrical impedance analysis. APFT results were provided by the ROTC
director. All assessment methods for percent body fat were strongly associated (r
>= 0.7, p < 0.01), implying that height and circumference measurement is a
practical tool to estimate percent body fat of ROTC cadets. Total APFT score was
not associated with any body fat assessment method. Push-up number was negatively
associated with percent body fat by all assessment methods (r >= -0.8, p =
0.001), although run time was positively associated (r >= 0.6, p < 0.05). This
suggests that percent body fat may be an important variable in determining or
improving cardiovascular and muscular endurance, but not APFT performance.
PMID- 27612346
TI - A Cross-Reactivity of Fenofibric Acid With MDMA DRI Assay.
AB - BACKGROUND: Within the framework of routine fitness examinations, French Air
Force military crew underwent urine testing for 3,4 methylenedioxymetamphetamine
(MDMA [ecstasy]). The cross-reactivity of a dyslipidemic drug, fenofibrate, with
an MDMA immunoassay was studied and confirmed on a large population sample.
METHODS: A 3-year retrospective study was performed on the MDMA DRI Ecstasy Assay
on the Unicel DXC 600. In the event of positive test result, a confirmatory
testing was carried out by gas chromatography/mass spectrometry (GC/MS) to
establish the presence of MDMA. When analysis by GC/MS did not confirm the
presence of MDMA, a false-positive result was suspected and the samples were
analyzed by high-performance liquid chromatography-mass spectrometry to identify
a potential interfering substance. RESULTS: A total of 15,169 urine samples, from
7,803 patients, were tested for 3 years. Of the tested samples, 22 (0.15%) were
positive by DRI Ecstasy Assay. None of them were positive by GC/MS. A cross
reactivity of fenofibrate's metabolite with MDMA using this assay was
systematically found. CONCLUSION: Fenofibrate's interference with MDMA
immunoassay was confirmed. Fenofibrate being widely prescribed, physicians had to
be alerted that this treatment could lead to false-positive results.
PMID- 27612347
TI - Caffeine Content in Popular Energy Drinks and Energy Shots.
AB - The use of energy beverages is high among the general population and military
personnel. Previous studies have reported discrepancies between the actual amount
of caffeine in products and the amount of caffeine on stated labels. Thus, the
purpose of this study was to examine the content of caffeine listed on the labels
of various energy drinks and energy shots. Top-selling energy drinks (n = 9) and
energy shots (n = 5) were purchased from retail stores. Three of each of the 14
products were purchased and analyzed for caffeine content by an independent
laboratory. Of the 14 products tested, 5 did not provide caffeine amounts on
their facts panel-of those, 3 listed caffeine as an ingredient and 2 listed
caffeine as part of a proprietary blend. The remaining 9 (of 14) products stated
the amounts of caffeine on their labels, all of which were within 15% of the
amount indicated on the label. In this study, although the energy beverages that
indicated the amount of caffeine it contained had values within +/-15% of the
amount listed on the label, a potentially acceptable range, this finding is not
acceptable with regard to current labeling regulations, which require added
ingredients to total 100%.
PMID- 27612349
TI - Integrative Pain Management Centers in the Military: The Challenges.
AB - OBJECTIVES: Biomedicine and complementary and alternative medicine are forming
new relationships, under the rubric of integrative medicine. Recently, the
military has adopted integrative medicine as the model for pain management. An
evaluation was conducted on an integrative model for pain management at a major
Army medical center to determine the distinct challenges that were encountered
during the early stages of this integrative program. METHODS: The design is a
case study evaluation. Qualitative data were analyzed to determine whether the
outcomes in terms of processes were in harmony with the program's mission. Study
participants were patients (34), referring providers (25), program staff (20),
administrators (18), and related medical center leadership (6). RESULTS: The
study uncovered the following challenges: misaligned culture and mission,
resources, the valuing of services (relative value units), systemic transition,
patient throughput, and stigma associated with the focus and location of the
program in a psychology department. CONCLUSIONS: These challenges prevented the
program from fully achieving its mission and potential. Although integrative
medicine might be the appropriate model for pain management in the military, the
structural and process elements to bring it about are not yet in place or fully
understood.
PMID- 27612350
TI - Suicidal Ideation is Associated With All-Cause Mortality.
AB - Suicidal ideation may be associated with all-cause mortality. Available research
shows that treatment of depression reduces the risk of all-cause mortality in
patients with suicidal ideation. However, this finding has not been replicated in
a clinical population, where patients have various mental health conditions. We
examined the association between suicidal ideation and all-cause mortality in a
clinical cohort. We stratified patients presenting to a mental health clinic from
January 2005 through December 2007 based upon their degree of suicidal ideation
and obtained vital status information through June 2015. We compared groups using
survival analysis, adjusting for patient characteristics and treatment receipt.
Among 1,869 patients who completed the initial assessment, there were 363 deaths.
Patients with the highest levels of suicidal ideation died at increased rates.
Cause-of-death data in the year following the initial assessment indicates that
the difference in mortality is not likely attributable to suicide. Accounting for
patient characteristics and treatment, which included medical care and mental
health care, did not meaningfully diminish the relationship between suicidal
ideation and all-cause mortality. Additional research is needed to determine
specific treatment elements that may moderate the relationship between suicidal
ideation and all-cause mortality.
PMID- 27612348
TI - Barriers to Initiating and Continuing Mental Health Treatment Among Soldiers in
the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
AB - U.S. Army soldiers with mental disorders report a variety of barriers to
initiating and continuing treatment. Improved understanding of these barriers can
help direct mental health services to soldiers in need. A representative sample
of 5,428 nondeployed Regular Army soldiers participating in the Army Study to
Assess Risk and Resilience in Servicemembers completed a self-administered
questionnaire and consented to linking self-administered questionnaire data with
administrative records. We examined reported treatment barriers (perceived need,
structural reasons, attitudinal reasons) among respondents with current
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, mental
disorders who either did not seek treatment in the past year (n = 744) or
discontinued treatment (n = 145). About 82.4% of soldiers who did not initiate
treatment and 69.5% of those who discontinued treatment endorsed at least two
barriers; 69.8% of never-treated soldiers reported no perceived need. Attitudinal
reasons were cited more frequently than structural reasons among never-treated
soldiers with perceived need (80.7% vs. 62.7%) and those who discontinued
treatment (71.0% vs. 37.8%). Multivariate associations with sociodemographic,
Army career, and mental health predictors varied across barrier categories. These
findings suggest most soldiers with mental disorders do not believe they need
treatment and those who do typically face multiple attitudinal and, to a lesser
extent, structural barriers.
PMID- 27612351
TI - School-Based Health Center Model Within the Military Health System: The Role of
the Adolescent Medicine Physician.
AB - Adolescents are less motivated to seek medical care for various reasons. Within
the military health care system, access barriers, although less encountered, can
still be a burden not only to the adolescent, but also the school system. This
article describes the development of a school-based health center within a school
district on a military installation. The school clinic was created by adolescent
medicine specialists to maximize access to care. Students of adolescent age
utilized the clinic for evaluation of acute and chronic conditions, preventative
services, preparticipation evaluation, and other general complaints. After
receiving signed consent forms, 30% of students were eligible for health care.
There was minimal cost to initiate the service. Development of school-based
health center programs at other military installations could potentially improve
the status of the military health system during a time of high stress among
military dependents.
PMID- 27612353
TI - Objective Evaluation of the Effects of Deployment on Laparoscopic Skills: The
Simulation and Deployment Laparoscopic Skills Study.
AB - OBJECTIVE: To assess the effects of deployment on basic laparoscopic skills of
general surgeons and obstetrics/gynecology (OB/GYN) physicians. METHODS: This was
a prospective 10-site study. Active duty Army OB/GYN and general surgery
physicians scheduled to deploy were invited to participate. Before deployment,
they performed fundamentals of laparoscopic surgery (FLS) tasks and specialty
specific procedures on a virtual reality laparoscopic simulator. Upon returning,
physicians repeated the same evaluations. Questions about perceived comfort with
laparoscopic procedures were asked before and after deployment. Statistical
analysis included paired t tests for continuous variables and nonparametric for
ordinal data with a p value of <0.05 considered significant. RESULTS: 121
deploying providers were invited to participate; 35 agreed and 29 completed the
predeployment skills assessment. After deployment, 15 providers had
postassessment evaluation data collected, and their results were used for
analysis. Though physicians reported a decrease in their perception of
preparedness for advanced laparoscopic procedures and complications, there was no
decrement in their performance of FLS tasks or the basic laparoscopic procedures.
CONCLUSION: Time away from regular clinical practice during deployments did not
significantly affect surgeons' performance as measured by a virtual reality
laparoscopic simulator. Additional study on effects on advanced procedures should
be considered.
PMID- 27612352
TI - Effects of Deployment on Musculoskeletal and Physiological Characteristics and
Balance.
AB - Despite many nonbattle injuries reported during deployment, few studies have been
conducted to evaluate the effects of deployment on musculoskeletal and
physiological characteristics and balance. A total of 35 active duty U.S. Army
Soldiers participated in laboratory testing before and after deployment to
Afghanistan. The following measures were obtained for each Soldier: shoulder,
trunk, hip, knee, and ankle strength and range of motion (ROM), balance, body
composition, aerobic capacity, and anaerobic power/capacity. Additionally,
Soldiers were asked about their physical activity and load carriage. Paired t
tests or Wilcoxon tests with an alpha = 0.05 set a priori were used for
statistical analyses. Shoulder external rotation ROM, torso rotation ROM, ankle
dorsiflexion ROM, torso rotation strength, and anaerobic power significantly
increased following deployment (p < 0.05). Shoulder extension ROM, shoulder
external rotation strength, and eyes-closed balance (p < 0.05) were significantly
worse following deployment. The majority of Soldiers (85%) engaged in physical
activity. In addition, 58% of Soldiers reported regularly carrying a load (22 kg
average). The deployment-related changes in musculoskeletal and physiological
characteristics and balance as well as physical activity and load carriage during
deployment may assist with proper preparation with the intent to optimize
tactical readiness and mitigate injury risk.
PMID- 27612354
TI - The Operative Burden of General Surgical Disease and Non-Battle Injury in a
Deployed Military Treatment Facility in Afghanistan.
AB - OBJECTIVES: Contemporary medical operations support a mobile, nonconventional
force involved in nation building, counterinsurgency, and humanitarian
operations. Prior reports have described surgical care for disease and nonbattle
injuries (DNBI). The purpose of this report is to describe the prevalence and
scope of DNBI managed by general surgeons in a contemporary, deployed medical
facility. METHODS: A 2-year retrospective review of the operative logbook from
the U.K. Role 3 Multinational Hospital, Camp Bastion, Afghanistan, was performed
to determine the prevalence and makeup of procedures performed for DNBI by
general surgeons. RESULTS: Nontrauma general surgical procedures accounted for
7.7% (n = 279 of 3,607 cases) of cases; appendectomy (n = 146) was the most
common, followed by drainage of soft tissue (n = 55) and oral abscesses (n = 5),
scrotal exploration (n = 12), and hernia repair (n = 7). A total of 7.2% (n = 20
of 279) of cases fell outside the standard scope of practice of an urban,
civilian general surgeon. CONCLUSION: Although the prevalence of operative
procedures for DNBI was low, the spectrum of cases included those not typically
managed in the civilian setting of the United Kingdom. With an evolving decline
in case volume performed in multiple anatomic locations due to subspecialization
during surgical training, this gap in expertise is likely to increase.
PMID- 27612355
TI - Dismounted Blast Injuries in Patients Treated at a Role 3 Military Hospital in
Afghanistan: Patterns of Injury and Mortality.
AB - BACKGROUND: The purposes of this study are to define the pattern of injuries
sustained by dismounted troops exposed to improvised explosive devices blasts
treated at a Role 3 combat support hospital and to assess injury patterns and
mortality associated with the mechanism. Our hypothesis was that mortality is
associated with pelvic fracture, massive transfusion, high Injury Severity Score
(ISS), multiple limb amputations, and transfer from a Role 2 facility. STUDY
DESIGN: Retrospective study of 457 patients. Analysis performed on trauma
registry data and systematic review of radiographs. RESULTS: 99.9% were men with
a median age of 23 years and median ISS 10. 141 patients (30.9%) required massive
blood transfusion. Limb amputations were frequently observed injuries, 109 of 172
amputees (63.4%) had a double amputation. 34 subjects (7.4%) had pelvic
fractures; majority of pelvic fractures (88%) were unstable (Tile B or C). Risk
factors associated with the overall mortality rate of 1.8% were an ISS greater
than 15 (odds ratio: 11.5; 95% confidence interval: 1.38, 533; p = 0.009), need
for massive transfusion (p < 0.0001), and the presence of a pelvic fracture (odds
ratio: 7.63; 95% confidence interval: 1.13, 41.3; p = 0.018). CONCLUSIONS:
Dismounted improvised explosive devices blast injuries result in devastating
multiple limb amputations and unstable pelvic fractures, which are associated
with mortality after initial trauma resuscitation at a Role 3 hospital.
PMID- 27612356
TI - Self-Management of Unreported Musculoskeletal Injuries in a U.S. Army Brigade.
AB - BACKGROUND: There is a paucity of literature describing the accuracy of
musculoskeletal injury reporting in the U.S. Army. PURPOSE: To investigate
symptom-management behaviors as well as factors associated with seeking medical
treatment among active duty Soldiers who reported that they had concealed at
least one musculoskeletal injury. METHODS: Anonymous surveys were completed by
Soldiers (N = 1,388; 1,269 males, 74 females, and 45 no response) assigned to an
Infantry Brigade Combat Team. Soldiers were asked to self-report injuries
sustained in the last 12 months and whether or not they reported those injuries
to a medical provider. Descriptive statistics were used to analyze treatment
alternatives. Chi-square test was used to assess any significant relationships
between injury and various demographics. RESULTS: There were 808 (58%) Soldiers
who stated they had an injury that they did not report. Over-the-counter pain
relief medication (81%) was the most commonly selected alternative treatment.
CONCLUSION: Over-the-counter pain medication was frequently used for symptom
management among Soldiers who did not report their injury to a medical provider.
PMID- 27612357
TI - Short-Term Results of a Rehabilitation Program for Service Members With Lower Leg
Pain and the Evaluation of Patient Characteristics.
AB - INTRODUCTION: Lower leg pain (LLP), including medial tibial stress syndrome
(MTSS) and chronic exertional compartment syndrome (CECS), remains a major
problem for the military. OBJECTIVE: Evaluation of patient characteristics and
short-term results of the rehabilitation program for service members used in the
Military Rehabilitation Centre Aardenburg. METHODS: This retrospective study
includes 161 service members of the Netherlands Armed Forces. Service members
were grouped into the following diagnostic categories: MTSS (n = 47),
conservative treatment of CECS (n = 34), and rehabilitation after operative
intervention of the CECS (CECSo; n = 80). RESULTS: The results showed a
significant improvement in all groups regarding the Patient-Specific Functional
Scale (PSFS). Only the CECSo group showed significant improvement on the Numeric
Pain Rating Score (NPRS). None of the patient characteristics like gender, age,
military service, duration of symptoms, and treatment setting were identified to
correlate with outcome results. CONCLUSIONS: Short-term results of the
rehabilitation program for service members with LLP are successful as obtained
with the PSFS. Evaluation by the NPRS seems insufficient and researchers should
consider using other outcome measurements. The CECSo group seems to benefit the
most from the rehabilitation program. No patient characteristics could be
identified to correlate with outcome results.
PMID- 27612358
TI - Military Medical Students' Awareness and Practice Concerning Occupational Health
and Safety.
AB - This study aimed to investigate the awareness and practices of military medical
students concerning occupational health and safety. In this cross-sectional
study, a questionnaire composed of 20 open- and closed-ended questions was
administered to medical students of the Gulhane Military Medical Faculty (n =
754). The response rate of the questionnaire was 82.4% (n = 622/754). The mean
age of the participants was 21.5 +/- 1.84 years, and the majority of participants
were male (94.1%). A substantial number of participants (41.1%) described their
level of awareness and practice as "low/very low," although 95.0% and 76.7% of
them had never acquired any occupational disease or had any work accidents,
respectively. In total, 28.1% of all students had at least one vaccination, and
5th- and 6th-year students were 92 times and 63 times more likely to have been
vaccinated than 1st-year students, respectively (odds ratio = 92.66, 95%
confidence interval = 26.70-321.59; odds ratio = 63.01, 95% confidence interval =
17.96-221.01). The knowledge and practice level of medical students concerning
occupational health and safety appeared to be increasing by the grades of medical
faculty, however students expressed themselves as insufficient about their
knowledge and practice level.
PMID- 27612359
TI - Self-Reported Changes in Comfort Level With Basic OB/GYN Procedures After
Deployment.
AB - OBJECTIVE: To assess the specialty-specific procedures and clinical encounters
U.S. Army obstetrician/gynecologist (OB/GYN) providers felt were affected by
deployment and identify skills and areas that may benefit from postdeployment
training. METHODS: Active duty Army OB/GYN physicians were invited to participate
in an anonymous web-based survey to rate their comfort level and experience
performing specialty-specific procedures before and after military deployment.
Physicians rated their comfort level on a 5-point Likert scale (1 = very
uncomfortable to 5 = completely comfortable). Statistical analysis included
Pearson chi(2) and McNemar's chi(2) with a p value of <0.05 considered
significant. RESULTS: Of the 100 physicians eligible to complete the survey, 66
responded (response rate = 66%). Their responses demonstrated a statistically
significant perception of decline in their comfort level with nearly every
obstetric and gynecologic procedure and clinical encounter evaluated. CONCLUSION:
Time away from regular clinical practice during deployment results in providers
feeling less comfortable with many common OB/GYN procedures and clinical
situations. Although these results are not a measure of actual performance, this
information helps define targets to focus refresher training for providers who
leave their normal scope of practice for deployment. These findings apply to
civilian providers leaving practice for other reasons as well.
PMID- 27612360
TI - Service Member Completion of Laboratory Follow-Up After Emergency Transfusion
With Freshly Collected Blood Products.
AB - BACKGROUND: Transfusion of freshly collected blood products (FCBP) is sometimes
necessary to save service member (SM) lives in austere deployed environments.
Recipients of FCBPs are administratively tracked and offered serial serologic
testing via the Armed Services Blood Program "Blood Look Back" (BLB) program to
assure early detection of post-transfusion infections. OBJECTIVES: This study
evaluates demographic and clinical features influencing SM completion of
recommended BLB laboratory follow-up after transfusion with FCBPs. METHODS: Using
BLB programmatic data, a retrospective cohort study was performed examining U.S.
SM transfusion recipients of FCBPs from June 1, 2006, through December 31, 2012.
Multivariate logistic regression was used to examine clinical and demographic
factors influencing completion of BLB recommended follow-up. RESULTS: Of eligible
subjects, 69% (n = 778) completed 12-month recommended BLB follow-up. As compared
to other services, U.S. soldiers demonstrated greatest compliance with BLB
recommendations with 71.7% completing recommended follow-up. As compared to the
Army, SMs from the Air Force (odds ratio [OR] = 0.35, 95% confidence interval
[CI] = 0.15-0.85), Marine Corps (OR = 0.51, 95% CI = 0.37-0.71), and Navy (OR =
0.29, 95% CI = 0.11-0.74) were less likely to complete recommended follow-up;
however, differences in follow-up among the services attenuated over time.
Neither the type of FCBP (platelets versus whole blood) nor the volume of FCBP
transfused significantly altered SM likelihood of competing recommended follow
up. CONCLUSIONS: More than 2 out of 3 SMs completed recommended 12-month BLB
follow-up after transfusion with FCBPs with greater compliance in Army SMs
compared to other services. Programmatic changes implemented by the BLB program
were temporally associated with increased SM compliance with recommended follow
up as well as reduction of disparities in follow-up observed between the
services.
PMID- 27612361
TI - Evaluation of Virulence Gene Expression Patterns in Acinetobacter baumannii Using
Quantitative Real-Time Polymerase Chain Reaction Array.
AB - According to the Centers for Disease Control's recently devised National Strategy
for Combating Antibiotic-Resistant Bacteria, Acinetobacter baumannii is a
"serious" threat level pathogen. A. baumannii's notoriety stems from the fact
that a large number of modern strains are multidrug resistant and persist in the
hospital setting, thus causing numerous deaths per year. It is imperative that
research focus on a more fundamental understanding of the factors responsible for
the success of A. baumannii. Toward this end, our group investigated virulence
gene expression patterns in a recently characterized wound isolate, AB5075, using
quantitative real-time polymerase chain reaction array. Notably, several genes
showed statistically significant upregulation at 37 degrees C compared to 25
degrees C; MviM, Wbbj, CarO, and certain genes of the Bas, Bar, and Csu operons.
Additionally, we found that in vitro biofilm formation by Csu transposon
insertion mutant strains is attenuated. These findings validate previous reports
that suggest a link between the Csu operon and biofilm formation. More
importantly, our results demonstrate a successful method for evaluating the
significance of previously identified virulence factors in a modern and
clinically relevant strain of A. baumannii, thereby providing a path toward a
more fundamental understanding of the pathogenicity of A. baumannii.
PMID- 27612362
TI - Fatty Acid Blood Levels, Vitamin D Status, Physical Performance, Activity, and
Resiliency: A Novel Potential Screening Tool for Depressed Mood in Active Duty
Soldiers.
AB - This study examined whether blood fatty acid levels, vitamin D status, and/or
physical activity are associated with physical fitness scores; a measure of mood,
Patient Health Questionnaire-9; and a measure of resiliency, Dispositional
Resiliency Scale-15 in active duty Soldiers. 100 active duty males at Fort Hood,
Texas, underwent a battery of psychometric tests, anthropometric measurements,
and fitness tests, and they also provided fasting blood samples for fatty acid
and vitamin D analysis. Pearson bivariate correlation analysis revealed
significant correlations among psychometric tests, anthropometric measurements,
physical performance, reported physical inactivity (sitting time), and fatty acid
and vitamin D blood levels. On the basis of these findings, a regression equation
was developed to predict a depressed mood status as determined by the Patient
Health Questionnaire-9. The equation accurately predicted depressed mood status
in 80% of our participants with a sensitivity of 76.9% and a specificity of
80.5%. Results indicate that the use of a regression equation may be helpful in
identifying Soldiers at higher risk for mental health issues. Future studies
should evaluate the impact of exercise and diet as a means of improving
resiliency and reducing depressed mood in Soldiers.
PMID- 27612363
TI - Lead Exposure in Military Outdoor Firing Ranges.
AB - BACKGROUND: Several studies have reported significant airborne lead exposures
during training at indoor firing ranges. Scarce attention has been given to
airborne lead exposures in outdoor shooting ranges with automatic weapons.
OBJECTIVE: To assess the prevalence and magnitude of airborne and blood lead
levels (BLL) among firing instructors and shooters in military outdoor ranges.
METHODS: Exposure assessment, for both trainees and instructors, included
airborne and BLL during basic and advanced training at outdoor firing ranges.
Personal airborne samples were collected in both day and night shooting during
both training periods. RESULTS: During basic training, there is 95% likelihood
that up to 25% of instructors and 99% likelihood that up to 5% of trainees might
be exposed above the action level (AL) (25 MUg/m(3)). During advanced training,
there is 90% likelihood that 10% of instructors and 99% likelihood that up to 10%
of trainees might be exposed above the AL. CONCLUSIONS: Military personnel
participating in automatic weapon marksmanship training can be exposed to
considerable levels of airborne lead during outdoor firing range training. As a
result, the Israel Defense Force Medical Corp has classified firing range
instructors as workers that require periodic medical examinations.
PMID- 27612365
TI - Effect of Stellate Ganglion Block on Specific Symptom Clusters for Treatment of
Post-Traumatic Stress Disorder.
AB - This study assessed which symptoms are most impacted following stellate ganglion
block (SGB) used to treat post-traumatic stress disorder (PTSD) symptoms. 30
active military service members with combat-related PTSD self-referred to their
physician and psychologist. Patients were offered a SGB as part of their
treatment program. Primary outcome was the magnitude of change for the 17 items
on the PTSD Checklist-Military (PCL-M), which was administered the week before
SGB, 1 week after SGB, and 2 to 4 months later. Mean PCL-M score decreased from
49 at baseline to 32, 1 week after the procedure (p < 0.001). 2 to 4 months after
SGB, patients maintained an average PCL-M of 32. Patients reported greatest
improvement in the first week after SGB for the following symptoms: irritability
or angry outbursts, difficulty concentrating, and sleep disturbance. 2 to 4
months later, patients reported greatest improvement in the following: feeling
distant or cut off, feeling emotionally numb, irritability or angry outbursts,
and difficulty concentrating. SGB is a safe procedure that may provide extended
relief for all clusters of PTSD symptoms. As a result of the significant
reduction in hyperarousal and avoidance symptoms observed, this study supports
incorporation of SGB into PTSD treatment plans.
PMID- 27612364
TI - Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea
in Veterans With Gulf War Illness.
AB - Despite the fact that sleep disturbances are common in veterans with Gulf War
Illness (GWI), there has been a paucity of published sleep studies in this
veteran population to date. Therefore, the present study examined subjective
sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia
severity (assessed with the Insomnia Severity Index), and risk for obstructive
sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans.
Veterans with GWI, defined either by the Kansas or Centers for Disease Control
and Prevention criteria, had greater risk for obstructive sleep apnea (i.e.,
higher STOP scores) than veterans without GWI. This difference persisted even
after accounting for potentially confounding demographic (e.g., age, gender) and
clinical variables. Veterans with GWI, defined by either the Kansas or Centers
for Disease Control and Prevention criteria, also had significantly greater
insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05),
even after accounting for potentially confounding variables. Furthermore, there
were significant, positive correlations between insomnia severity, subjective
sleep quality, and GWI symptom severity (p <= 0.01). In stepwise linear
regression models, insomnia severity significantly predicted GWI status over and
above demographic and clinical variables. Together these findings provide good
rationale for treating sleep disturbances in the management of GWI.
PMID- 27612366
TI - Planning Military Drinking Water Needs: Development of a User-Friendly Smart
Device Application.
AB - Potable water is essential to maintain health and sustain military operations,
but carrying and transporting water is a major logistical burden. Planning for
group drinking water needs is complex, requiring understanding of sweat losses on
the basis of intensity of activity, clothing biophysical parameters, and
environmental conditions. Use of existing prediction equations is limited to
tabled doctrine (e.g., Technical Bulletin, Medical 507) or to individuals with
extensive expertise in thermal biophysics. In the present project, we translated
the latest updated equations into a user-friendly Android application (Soldier
Water Estimation Tool, SWET) that provides estimated drinking water required from
5 simple inputs based upon a detailed multiparametric sensitivity analysis. Users
select from multiple choice inputs for activity level, clothing, and cloud cover,
and manually enter exact values for temperature and relative humidity. Total
drinking water needs for a unit are estimated in the Mission Planner tool on the
basis of mission duration and number of personnel. In preliminary user
acceptability testing, responses were overall positive in terms of ease of use
and military relevance. Use of SWET for water planning will minimize excessive
load (water) carriage in training and mission settings, and will reduce the
potential for dehydration and/or hyponatremia to impair Warfighter health and
performance.
PMID- 27612367
TI - Toward Preventing Post-Traumatic Stress Disorder: Development and Testing of a
Pilot Predeployment Stress Inoculation Training Program.
AB - The objective of this pilot study was to design, develop, and evaluate a
predeployment stress inoculation training (PRESIT) preventive intervention to
enable deploying personnel to cope better with combat-related stressors and
mitigate the negative effects of trauma exposure. The PRESIT program consisted of
three predeployment training modules: (1) educational materials on combat and
operational stress control, (2) coping skills training involving focused and
relaxation breathing exercises with biofeedback, and (3) exposure to a video
multimedia stressor environment to practice knowledge and skills learned in the
first two modules. Heart rate variability assessed the degree to which a subset
of participants learned the coping skills. With a cluster randomized design, data
from 351 Marines randomized into PRESIT and control groups were collected at
predeployment and from 259 of these who responded to surveys on return from
deployment. Findings showed that the PRESIT group reduced their physiological
arousal through increased respiratory sinus arrhythmia during and after breathing
training relative to controls. Logistic regression, corrected for clustering at
the platoon level, examined group effects on post-traumatic stress disorder
(PTSD) as measured by the Post-traumatic Stress Checklist after controlling for
relevant covariates. Results showed that PRESIT protected against PTSD among
Marines without baseline mental health problems. Although limited by a small
number of participants who screened positive for PTSD, this study supports the
benefits of PRESIT as a potential preventive strategy in the U.S. military
personnel.
PMID- 27612368
TI - A Civil War Identity Theft?
PMID- 27612369
TI - Maintaining Military Readiness: Should the Way We Train Change?
PMID- 27612370
TI - Need for Routine Vitamin D Screening in Military Personnel.
PMID- 27612371
TI - Installation Tobacco Control Programs in the U.S. Military.
PMID- 27612372
TI - Changes in Cardiovascular Performance During an 8-Week Military Basic Training
Period Combined with Added Endurance or Strength Training.
PMID- 27612373
TI - Misdiagnosis of Exertional Heat Stroke and Improper Medical Treatment.
PMID- 27612374
TI - Attrition Due to Orthopedic Reasons During Combat Training: Rates, Types of
Injuries, and Comparison Between Infantry and Noninfantry Units.
PMID- 27612375
TI - Omega-3 Fatty Acids and Stress-Induced Immune Dysregulation: Implications for
Wound Healing.
PMID- 27612376
TI - Reproductive Health of Active Duty Women in Medically Austere Environments.
PMID- 27612377
TI - Mission Compromised? Drug-Induced Liver Injury From Prohormone Supplements
Containing Anabolic-Androgenic Steroids in Two Deployed U.S. Service Members.
AB - BACKGROUND: Supplement adulteration with anabolic-androgenic steroids (AAS) has
been reported and AAS-associated drug-induced liver injury is clinically
variable. OBJECTIVES: We present two cases of AAS-associated drug-induced liver
injury in deployed service members, including the first report of clinical
hepatotoxicity with desoxymethyltestosterone. We highlight variable
hepatotoxicity patterns of AAS, raise concern with inaccurate supplement labeling
and identify educational resources. METHODS: The first case presents with
cholestatic jaundice following 10 weeks of prohormone use. Hepatobiliary imaging
was unrevealing. Viral, autoimmune, and metabolic etiologies were excluded.
Bilirubin normalized by 8 weeks after stopping the supplement. The second case
presents with asymptomatic hepatocellular toxicity and marked dyslipidemia
identified on service-related physical following 21 days of prohormone use.
Aspartate aminotransferase and alanine aminotransferase normalized 4 weeks after
supplement cessation; high-density lipoprotein and low-density lipoprotein
returned to baseline at 8 weeks. Each supplement was volunteered for analytic
testing. RESULTS: Supplement label contents did not match gas chromatography/mass
spectrometry analysis; 3 of 4 supplements contained federally regulated AAS.
CONCLUSIONS: AAS hepatotoxicity is clinically variable and dyslipidemia may be an
important clinical indicator. False labeling introduces clinical risk and
threatens mission readiness. Educational resources are available to facilitate
information sharing. Supplement analysis informs of clinical risk of specific
supplements and facilitates shared clinical decision-making.
PMID- 27612378
TI - Pelvic Floor Reconstruction Utilizing a Residual Hamstring Rotational Flap
Following Traumatically Induced Subtotal Hemipelvectomy in a Combat Blast
Casualty: A Case Report.
AB - OBJECTIVE: There are several options for soft tissue coverage following external
hemipelvectomy; however, in cases of war-related blast trauma, standard flaps are
not always available as a result of the extensive soft tissue damage. METHODS: We
detail a novel closure technique following a subtotal hemipelvectomy with exposed
abdominal viscera using a residual hamstring myofascial cutaneous flap. RESULTS:
This flap allowed for fascial tissue to fill the pelvic defect and provided
excellent soft tissue coverage for future prosthetic wear. DISCUSSION: In the
current literature, there is limited information regarding surgical options for
soft tissue coverage following traumatic hip disarticulation. Most cases result
from malignancies or severe infection, where tissue distal to the lesion is
viable and provides adequate coverage. This case report used a novel technique,
provided excellent soft tissue coverage with no wound healing complications,
allowed for excellent prosthetic fitting, and the patient's ability to ambulate
without assistance.
PMID- 27612379
TI - A Quadricuspid Aortic Valve as Seen by Cardiac Magnetic Resonance Imaging.
AB - We report a case of a 35-year-old active duty male with a rare quadricuspid
aortic valve identified via transthoracic echocardiography following the
detection of an incidental grade I/VI diastolic murmur. Further characterization
of the anatomical findings and aortic valve flow dynamics were evaluated with
cardiac magnetic resonance imaging. Accurate assessment of the various valve
morphologies is essential, as it guides surgical treatment options to correct the
defect. Our case highlights the complimentary role of cardiac magnetic resonance
imaging in defining the anatomy and functional consequences of a quadricuspid
aortic valve.
PMID- 27612380
TI - Conservative Management of an Intraoperative Chyle Leak: A Case Report and
Literature Review.
AB - Chyle leaks are a rare but potentially fatal complication of head and neck
surgery carrying an incidence as high as 8.3%. The development of a chyle leak
carries significant morbidity ranging from delayed wound healing to oropharyngeal
fistulas. Presented here is a case of a chyle leak that developed following a
left posterolateral neck dissection that was successfully managed with a
combination of drain suction, pressure dressing, and a fat-restricted diet.
However, the patient's course was complicated by repeated chyle leak recurrences
that may have been associated with the initiation of medium-chain triglyceride
supplementation. Although further research is required to establish a causal
relationship, these findings support the concerns of other investigators about
the possible counterproductive role of medium-chain triglyceride supplementation
in the management of chyle leaks.
PMID- 27612381
TI - Serotonin Syndrome Following an Uncomplicated Orthopedic Surgery in a Patient
With Post-Traumatic Stress Disorder.
AB - Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction
that may occur in patients treated with serotonin agonist medications.
Medications responsible for serotonin syndrome include commonly prescribed
antidepressants, anxiolytics, analgesics, and antiemetics. Veterans with post
traumatic stress disorder (PTSD) are at risk for polypharmacy with serotoninergic
medications, given their psychological comorbidities and service-related
musculoskeletal injuries. The perioperative period is a particularly vulnerable
time owing to the use of high-dose anxiolytics and antiemetics frequently
administered in this period, and places PTSD patients at higher risk of SS.
Herein, we present the first case of SS in a young veteran with combat-related
PTSD following an uncomplicated L5-S1 revision discectomy that highlights the
unique set of clinical challenges and dilemmas faced when treating SS in a
patient with severe postsurgical pain. As we are likely to encounter increasing
numbers of veterans treated for PTSD who require multiple surgical procedures to
treat their service-related injuries, health care providers need to be familiar
with prevention, recognition, and the clinical challenges in the management of SS
in the postoperative period.
PMID- 27612383
TI - Regulation of starvation-induced hyperactivity by insulin and glucagon signaling
in adult Drosophila.
AB - Starvation induces sustained increase in locomotion, which facilitates food
localization and acquisition and hence composes an important aspect of food
seeking behavior. We investigated how nutritional states modulated starvation
induced hyperactivity in adult Drosophila. The receptor of the adipokinetic
hormone (AKHR), the insect analog of glucagon, was required for starvation
induced hyperactivity. AKHR was expressed in a small group of octopaminergic
neurons in the brain. Silencing AKHR+ neurons and blocking octopamine signaling
in these neurons eliminated starvation-induced hyperactivity, whereas activation
of these neurons accelerated the onset of hyperactivity upon starvation. Neither
AKHR nor AKHR+ neurons were involved in increased food consumption upon
starvation, suggesting that starvation-induced hyperactivity and food consumption
are independently regulated. Single cell analysis of AKHR+ neurons identified the
co-expression of Drosophila insulin-like receptor (dInR), which imposed
suppressive effect on starvation-induced hyperactivity. Therefore, insulin and
glucagon signaling exert opposite effects on starvation-induced hyperactivity via
a common neural target in Drosophila.
PMID- 27612382
TI - Hedgehog signaling regulates gene expression in planarian glia.
AB - Hedgehog signaling is critical for vertebrate central nervous system (CNS)
development, but its role in CNS biology in other organisms is poorly
characterized. In the planarian Schmidtea mediterranea, hedgehog (hh) is
expressed in medial cephalic ganglia neurons, suggesting a possible role in CNS
maintenance or regeneration. We performed RNA sequencing of planarian brain
tissue following RNAi of hh and patched (ptc), which encodes the Hh receptor. Two
misregulated genes, intermediate filament-1 (if-1) and calamari (cali), were
expressed in a previously unidentified non-neural CNS cell type. These cells
expressed orthologs of astrocyte-associated genes involved in neurotransmitter
uptake and metabolism, and extended processes enveloping regions of high synapse
concentration. We propose that these cells are planarian glia. Planarian glia
were distributed broadly, but only expressed if-1 and cali in the neuropil near
hh+ neurons. Planarian glia and their regulation by Hedgehog signaling present a
novel tractable system for dissection of glia biology.
PMID- 27612386
TI - Transparent reporting of research results in eLife.
AB - Manuscripts should include all the experimental and statistical details that are
needed to replicate the experiments and analyses reported in them.
PMID- 27612384
TI - A functional genomics screen in planarians reveals regulators of whole-brain
regeneration.
AB - Planarians regenerate all body parts after injury, including the central nervous
system (CNS). We capitalized on this distinctive trait and completed a gene
expression-guided functional screen to identify factors that regulate diverse
aspects of neural regeneration in Schmidtea mediterranea. Our screen revealed
molecules that influence neural cell fates, support the formation of a major
connective hub, and promote reestablishment of chemosensory behavior. We also
identified genes that encode signaling molecules with roles in head regeneration,
including some that are produced in a previously uncharacterized parenchymal
population of cells. Finally, we explored genes downregulated during planarian
regeneration and characterized, for the first time, glial cells in the planarian
CNS that respond to injury by repressing several transcripts. Collectively, our
studies revealed diverse molecules and cell types that underlie an animal's
ability to regenerate its brain.
PMID- 27612385
TI - Human DNA2 possesses a cryptic DNA unwinding activity that functionally
integrates with BLM or WRN helicases.
AB - Human DNA2 (hDNA2) contains both a helicase and a nuclease domain within the same
polypeptide. The nuclease of hDNA2 is involved in a variety of DNA metabolic
processes. Little is known about the role of the hDNA2 helicase. Using bulk and
single-molecule approaches, we show that hDNA2 is a processive helicase capable
of unwinding kilobases of dsDNA in length. The nuclease activity prevents the
engagement of the helicase by competing for the same substrate, hence prominent
DNA unwinding by hDNA2 alone can only be observed using the nuclease-deficient
variant. We show that the helicase of hDNA2 functionally integrates with BLM or
WRN helicases to promote dsDNA degradation by forming a heterodimeric molecular
machine. This collectively suggests that the hDNA2 motor promotes the enzyme's
capacity to degrade dsDNA in conjunction with BLM or WRN and thus promote the
repair of broken DNA.
PMID- 27612387
TI - Visceral adipose tissue: A clue to the obesity-asthma endotype(s)?
PMID- 27612388
TI - Advancing palliative and end-of-life science in cardiorespiratory populations:
The contributions of nursing science.
AB - Nursing science has a critical role to inform practice, promote health, and
improve the lives of individuals across the lifespan who face the challenges of
advanced cardiorespiratory disease. Since 1997, the National Institute of Nursing
Research (NINR) has focused attention on the importance of palliative and end-of
life care for advanced heart failure and advanced pulmonary disease through the
publication of multiple funding opportunity announcements and by supporting a
cadre of nurse scientists that will continue to address new priorities and future
directions for advancing palliative and end-of-life science in cardiorespiratory
populations.
PMID- 27612389
TI - Investigation of the Li-S Battery Mechanism by Real-Time Monitoring of the
Changes of Sulfur and Polysulfide Species during the Discharge and Charge.
AB - The mechanism of the sulfur cathode in Li-S batteries has been proposed. It was
revealed by the real-time quantitative determination of polysulfide species and
elemental sulfur by means of high-performance liquid chromatography in the course
of the discharge and recharge of a Li-S battery. A three-step reduction mechanism
including two chemical equilibrium reactions was proposed for the sulfur cathode
discharge. The typical two-plateau discharge curve for the sulfur cathode can be
explained. A two-step oxidation mechanism for Li2S and Li2S2 with a single
chemical equilibrium among soluble polysulfide ions was proposed. The chemical
equilibrium among S52-, S62-, S72-, and S82- throughout the entire oxidation
process resulted for a single flat recharge curve in Li-S batteries.
PMID- 27612390
TI - Predictors of Satisfaction With Doctor and Nurse Communication: A National Study.
AB - Prior research indicates that effective communication between medical providers
and patients is associated with a number of positive patient outcomes, yet little
research has examined how ecological factors (e.g., hospital size, local
demographics) influence patients' reported satisfaction with doctor and nurse
communication. Given the current emphasis on improving patient satisfaction in
hospitals across the United States, understanding these factors is critical to
interpreting patient satisfaction and improving patient-centered communication,
particularly in diverse and dense populations. As such, this study examined
county-level data including population density, population diversity, and
hospital structural factors as predictors of patient satisfaction with doctor and
nurse communication. Hospital Consumer Assessment of Healthcare Providers and
Systems (HCAHPS), U.S. Census data, and number of hospital beds were obtained
from publicly available Hospital Compare, U.S. Census, and American Hospital
Directory websites, respectively. Multivariate regression modeling was performed
for the individual dimensions of HCAHPS scores assessing doctor and nurse
communication. Standardized partial regression coefficients were used to assess
strengths of county-level predictors. County-level factors accounted for 30% and
16% of variability in patient satisfaction with doctor and nurse communication,
respectively. College education (beta = 0.45) and White ethnicity (beta = 0.25)
most strongly predicted a favorable rating of doctor and nurse communication,
respectively. Primary language (non-English speaking; beta = -0.50) most strongly
predicted an unfavorable rating of doctor communication, while number of hospital
beds (beta = -0.16) and foreign-born (beta = -0.16) most strongly predicted an
unfavorable rating of nurse communication. County-level predictors should be
considered when interpreting patient satisfaction with doctor and nurse
communication and designing multilevel patient-centered communication improvement
strategies. Discordant findings with individual-level factors should be explored
further.
PMID- 27612391
TI - Comment to "Benign prostatic hyperplasia and lower urinary tract symptoms. A
review of current evidence".
PMID- 27612392
TI - A mixed treatment meta-analysis of antibiotic treatment options for bovine
respiratory disease - An update.
AB - Bovine respiratory disease is the most economically important disease of feedlot
cattle in North America. Choice of antibiotic is a critical factor for producers
and veterinarians. We previously published a mixed-treatment comparison meta
analysis that combined evidence from published trials and published estimates of
comparative efficacy for 12 antibiotics registered for use in the USA. Some of
the comparative efficacy estimates were based only on indirect evidence. Since
the original review was published, new studies that provide direct evidence of
comparative efficacy have been published. We updated the original review to
include the current evidence. We also compared the results from the indirect
estimates from the prior model with the observed results from randomized control
trials. We repeated the original search and found that five of the new studies
met the criteria for inclusion in the updated review. Four of these studies
provided new data on direct comparisons of active drugs. The results from one
study (performed in 2002) that compared ceftiofur pinna and enrofloxacin were
inconsistent with the network and were excluded from the analysis. Three new
direct comparison studies examined gamithromycin compared with tulathromycin,
florfenicol, and tilmicosin. The results of our analysis suggested that the
indirect estimates from the prior model provided reasonable estimates of the risk
ratios revealed by the primary studies. For example, for the comparison of
gamithromycin (referent) with tulathromycin, the original model predicted a risk
ratio of re-treatment of 0.54 (95% credible interval 0.27-0.87). The subsequent
randomized controlled trial revealed that the observed risk ratio of re-treatment
was 0.59 (95% confidence interval 0.45-0.78). The results of other comparisons
were also similar. For the gamithromycin (referent) to florfenicol comparison,
the observed randomized trial RR was 1.17 (95% confidence interval 0.83-1.64) and
the indirect estimate of RR from the prior model was 0.84 (95% credibility
interval 0.48-1.3). The gamithromycin to tilmicosin (referent) observed RR from
the randomized trial was 0.99 (95% confidence interval 0.67-1.47) and the
indirect estimate of RR from the prior model was 1.09 (95% credible interval 0.64
1.79). The results suggested that indirect estimates provided reasonable
estimates of RR when direct data were not available.
PMID- 27612393
TI - 4-(6,7-Dihydro-5H-indeno[5,6-d] thiazol-2-yl)benzene-1,3-diol prevents UV-induced
melanogenesis and wrinkle formation in HRM-2 hairless mice.
PMID- 27612394
TI - Activation of the receptor for advanced glycation end products and consequences
on health.
AB - Advanced glycation end products (AGE) resulted from a reaction between free amino
group of proteins and carbohydrates. This reaction is followed by oxidation and
molecular rearrangement. Alternatively AGEs can be produced by glycolysis and
oxidation. AGEs bind to a cellular receptor RAGE. RAGE engagement by ligands AGE,
beta-amyloid peptide, and S100 calgranulin induces a stimulation of NADPH
oxidase, reactive oxygen intermediate formation, NFkappaB activation and gene
transcription. This cascade of reaction leads to an inflammatory reaction
responsible for alteration of microvessels in the retina and the kidney. Blockade
of RAGE by antibodies anti-RAGE, TTP488 (azeliragon), or rRAGE prevents or limits
the deleterious effect of AGEs.
PMID- 27612395
TI - Sleep-disordered breathing and disorders of glucose metabolism.
AB - AIMS: The authors identified the risk of disorders of glucose metabolism (DGM)
for sleep-disordered breathing (SDB). METHODS: We conducted a cross-sectional
study in 536 men aged 33-84 years. Patients with diabetes medication were
excluded for the analysis and DGM were diagnosed by fasting plasma
glucose>=100mg/dl and/or 2h plasma glucose >=140mg/dl. RESULTS: The prevalence of
DGM in subjects with and without severe SDB, which was judged by an apnea
hypopnea index (AHI) of 30, were 64.9% and 53.3%, which showed no significant
difference. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of
the logarithmic-transformed AHI and that of C-reactive protein for DGM were 1.3
(0.87-2.0) and 2.3 (1.5-3.6), respectively. When the subjects were categorized by
the severity of SDB, the ORs (95% CIs) of subjects with mild, moderate and severe
SDB against subjects without SDB were 2.9 (1.8-4.6), 1.2 (0.72-2.1) and 1.5 (0.8
3.0), respectively. CONCLUSION: A significant association was observed between
mild SDB and the presence of DGM in male subjects of this study.
PMID- 27612396
TI - Design, developing and validation a questionnaire to assess general population
awareness about type II diabetes disease and its complications.
AB - BACKGROUND: Timely prevention of type 2 diabetes decrease socio-economic burden
of disease in a society. To measure people's knowledge, the existence of valid
and accurate tool such as questionnaires is very important. In the study we tried
to make a comprehensive questionnaire to measure knowledge of apparently healthy
individuals. MATERIAL AND METHODS: In this study a questionnaire to assess
general population awareness about type II diabetes disease and its complications
was Design, developing and validation based on 10 experts' panel and statistical
inferences. RESULTS: Initially 67 questions designed and according to the
experts' panel 16 questions were removed and 11 questions were edited. Finally,
content validity of 51 questions has been approved by the experts' panel.
According to Lawshe's score if CVRs were at least 0.8, items will be has content
validity. The results show that both internal consistency and intra-class
correlation were good (>0.75). Cronbach's alpha and ICC were 0.84 and 0.82,
respectively for all questions. To confirm structure of conceptual model,
confirmatory factor analysis and Amos software was used. Goodness of Fit Index
was RMSEA=0.027, GFI=0.95, AGFI=0.91, CFI=0.97; and showed that the hypothesized
model is approved. CONCLUSION: In general, we can say that the questionnaire is
approximately comprehensive and complete. It is suggested that to assess
awareness of diabetes type 2 in seven dominants (e.g. fundamentals, common
symptoms, early and late complications, diet, control methods, and source of
information of DMT2) this questionnaire should be used in general population.
PMID- 27612398
TI - Corrigendum to "Circulating midkine in children with Henoch-Schonlein purpura:
Clinical implications" [Int. Immunopharmacol. (2016) 246-250].
PMID- 27612397
TI - Assessment of arterial stiffness in patients with metabolic syndrome in Ecuador:
A cross-sectional study.
AB - BACKGROUND: Metabolic syndrome increases cardiovascular risk, and causes damage
to the vascular wall. Through this mechanism, it might increase arterial
rigidity, leading to further complications and heart strain. The use of a device
that measures arterial rigidity can help determine if metabolic syndrome is
related to a higher vascular stiffness and changes in estimated arterial age.
METHODOLOGY: Cross-sectional study at Luis Vernaza hospital of Guayaquil,
Ecuador. Inpatients and outpatients from the Department of Cardiology with a full
blood panel and echocardiogram were included. We used the IDF criteria to
diagnose metabolic syndrome and measured arterial rigidity parameters in all of
them, including augmentation indexes, central blood pressure, pulse wave velocity
and arterial age. RESULTS: 95 patients were included for analysis, 44.2% were
females and 55.8% were males. Mean age was 61.7 years (+/-13.1). Metabolic
syndrome was diagnosed in 49.5% of our patients and it was significantly more
prevalent in women. We found significant differences in PWV, augmentation
indexes, and peripheral and central blood pressure between metabolic and non
metabolic syndrome patients. There was a non-significant relationship between
estimated arterial age and metabolic syndrome (p=0.32). CONCLUSION: Patients with
metabolic syndrome have an increased arterial rigidity. This, added to the high
prevalence of the disease we found in our sample, shows the high cardiovascular
risk these patients are at. A multidisciplinary approach to management is needed,
along with patient collaboration. The introduction of these devices to measure
arterial stiffness in developing countries can improve diagnosis and therapy of
patients with cardio-metabolic conditions.
PMID- 27612399
TI - Autoinflammatory associated vasculitis.
AB - Autoinflammatory diseases are characterized by recurrent episodes of fever and
localized or systemic inflammation and are caused by monogenic defects of innate
immunity. The skin is commonly involved with various manifestations including
erysipelas like rash and urticaria. Although vasculitis has been described in
many autoinflammatory diseases, it has not been recognized as a characteristic
feature of these diseases and autoinflammatory diseases are not listed as an
etiology for vasculitis associated with a systemic disease in the 2012 Revised
International Chapel Hill Consensus Conference Nomenclature of Vasculitides. We
describe herein 3 patients with different autoinflammatory diseases in whom
leukocytoclastic vasculitis was one of the major and presenting symptoms. A
review of the vast evidence in the literature for vasculitis in the spectrum of
autoinflammatory diseases and a suggested pathophysiology is presented. We
suggest the term autoinflammatory associated vasculitis to describe vasculitis
associated with autoinflammatory diseases. Autoinflammatory diseases should be
considered within the differential diagnosis of vasculitis.
PMID- 27612402
TI - Supporting a child with multiple disabilities to participate in social
interaction: The case of asking a question.
AB - Asking a question can be a highly challenging task for a person with multiple
disabilities, but questions have not received much attention in research on
augmentative and alternative communication (AAC). Conversation analysis is
employed to examine an instance of multiparty interaction where a speech and
language therapist supports a child with multiple disabilities to ask a question
with a communication board. The question is accomplished through a practice where
the action is built as a trajectory of interactional steps. Each step is built
using ways of involvement that establish different participation spaces designed
to deal with different aspects of asking a question: agreeing on the action type,
the speaker and recipient, the content of the question, and then asking the
question. The segmentation of a question into discrete steps and participation
spaces can be used in intervention to model the construction of a question for
AAC users and significant others.
PMID- 27612401
TI - Rapid start-up of the anammox process: Effects of five different sludge
extracellular polymeric substances on the activity of anammox bacteria.
AB - This study investigated the rapid start-up of the anaerobic ammonium oxidation
(anammox) strategy by inoculating different biomass ratios of denitrifying
granular sludge and anammox bacteria. The results demonstrated that two reactors
(R1 and R2) were rapidly and successfully started-up on days 25 and 28,
respectively, with nitrogen removal rates (NRRs) of 0.70kg/(m(3).d) and
0.72kg/(m(3).d) at biomass ratios of 10:1 (R1) and 50:1 (R2). The explanation for
rapid start-up was found by examining the effect of five different sludge
extracellular polymeric substances (EPS) on the activity of anammox bacteria in
the batch experiments. Batch experiments results first demonstrated that the
denitrification sludge EPS (DS-EPS) enhanced the anammox bacteria activity the
most, and NO2(-)-N, NH4(+)-N removal rates were 1.88- and 1.53-fold higher than
the control with optimal DS-EPS volume of 10mL. The rapid start-up strategy makes
possible the application of anammox to practical engineering.
PMID- 27612400
TI - Risk stratification and immunogenetic risk for infections following stem cell
transplantation.
AB - Patients undergoing haematopoietic stem cell transplantation (HSCT) are highly
exposed to infectious agents. However, it is not known why certain HSCT
recipients rapidly develop severe infections while other, despite similar
immunosuppressive conditions, do not. Increasing evidence suggests that such
differences may be due, in part, to polymorphisms in immune genes. Thus, the
identification of genetic factors influencing susceptibility to infections in
HSCT recipients may lead to the development of individualized management
strategies. However, studies are challenged by several issues, including the
relative small size of existing cohorts, the frequent use of prophylactic or
preemptive antimicrobial agents, and the fact that genes responsible for immune
functions can be inherited either from the donor or the host. Consequently, the
major challenge for today's researchers is to overcome these limitations and find
associations that are robust enough to be translated into reliable risk
stratification strategies for infectious diseases.
PMID- 27612403
TI - Anthropometric standards for Australian primary school children: Towards a system
for monitoring and supporting children's development.
AB - OBJECTIVES: To provide two foundation elements of a proposed new system to
support children's physical and body status development throughout primary
school: (a) age and gender appropriate achievement (anthropometric) standards and
(b) a system of monitoring, feedback and support. DESIGN: Repeated cross
sectional sampling involving 91 schools across 5 Australian States and
Territories between 2000 and 2011. METHODS: Anthropometric data from 29,928
(14,643 girls, 15,285 boys) Australian children aged between 5 and 12.5 years
were used to develop progression standards (norm centiles) covering the primary
school years. Measures used were: height, weight, body mass index, per cent body
fat, grip strength, standing long jump, cardiorespiratory fitness, sit-ups and
sit-and-reach. These norms were then used to develop a Physical Activity and
Lifestyle Management (PALM) system that could form the basis for progression,
monitoring and reporting of anthropometric achievement standards for children.
RESULTS: Tables and representative centile curves (3rd, 15th, 50th, 85th and
97th) for each gender and half-year age group were produced. An illustrative
example of the PALM system in operation was also provided. CONCLUSIONS: Our
research provides gender and half-year age specific anthropometric standards for
Australian primary school children. Furthermore, we have developed a monitoring
and progression system that could be embedded in school communities to help
address the prevalence of underweight, overweight and obesity and decline in
physical fitness standards. The proposed system is designed on behalf of children
and families and would be administered through school settings. Change, where
needed, would be delivered by the supporting school community.
PMID- 27612404
TI - A complex proximal femoral fracture.
AB - We present the case of a 39-year-old sportswoman who was involved in a motorcycle
accident in 2012. She sustained a complex proximal femoral fracture that involved
the neck and trochanteric region. We decided to preserve the natural bone stock
and repair the fractures, adopting skeletal traction in the first stage and then
implanting an intramedullary nail. Twenty months later the fracture was healed
clinically and radiologically and the patient was able to walk and run without
pain.
PMID- 27612405
TI - Patterning of papillae on the mouse tongue: A system for the quantitative
assessment of planar cell polarity signaling.
AB - The dorsal surface of the mouse tongue is covered by ~7000 papillae, asymmetric
epithelial protrusions that are precisely oriented to create a stereotyped
macroscopic pattern. Within the context of this large-scale pattern, neighboring
papillae exhibit a high degree of local order that minimizes the differences in
their orientations. We show here that the orientations of lingual papillae are
under the control of the core planar cell polarity (PCP) genes Vangl1, Vangl2,
and Celsr1. Using K14-Cre and Nkx2.5-Cre to induce conditional knockout of Vangl1
and/or Vangl2 in the tongue epithelium, we observe more severe disruptions to
local order among papillae with inactivation of larger numbers of Vangl genes, a
greater role for Vangl2 than Vangl1, and a more severe phenotype with the Vangl2
Looptail (Lp) allele than the Vangl2 null allele, consistent with a dominant
negative mode of action of the Vangl2Lp allele. Interestingly, Celsr1-/- tongues
show disruption of both local and global order, with many papillae in the
anterior tongue showing a reversed orientation. To quantify each of these
phenotypes, we have developed and applied three procedures for sampling the
orientations of papillae and assessing the degree of order on different spatial
scales. The experiments reported here establish the dorsal surface of the mouse
tongue as a favorable system for studying PCP control of epithelial patterning.
PMID- 27612406
TI - Overview on mechanisms of isoniazid action and resistance in Mycobacterium
tuberculosis.
AB - Isoniazid (INH) is one of the most active compounds used to treat tuberculosis
(TB) worldwide. In addition, INH has been used as a prophylactic drug for
individuals with latent Mycobacterium tuberculosis (MTB) infection to prevent
reactivation of disease. Importantly, the definition of multidrug resistance
(MDR) in TB is based on the resistance of MTB strains to INH and rifampicin
(RIF). Despite its simple chemical structure, the mechanism of action of INH is
very complex and involves several different concepts. Many pathways pertaining to
macromolecular synthesis are affected, notably mycolic acid synthesis. The pro
drug INH is activated by catalase-peroxidase (KatG), and the active INH products
are targeted by enzymes namely, enoyl acyl carrier protein (ACP) reductase (InhA)
and beta-ketoacyl ACP synthase (KasA). In contrast, INH is inactivated by
arylamine N-acetyltransferases (NATs). Consequently, the molecular mechanisms of
INH resistance involve several genes in multiple biosynthetic networks and
pathways. Mutation in the katG gene is the major cause for INH resistance,
followed by inhA, ahpC, kasA, ndh, iniABC,fadE, furA, Rv1592c and Rv1772. The
recent association of efflux genes with INH resistance has also gained
considerable attention. Interestingly, substitutions have also been observed in
nat, fabD, and accD recently in resistant isolates. Understanding the mechanisms
operating behind INH action and resistance would enable better detection of INH
resistance. This information would aid novel drug design strategies. Herein we
review all mechanisms known to potentially contribute to the complexity of INH
action and mechanisms of resistance in MTB, with insights into methods for
detection of INH resistance as well as their limitations.
PMID- 27612407
TI - Therapeutic RNAi robed with ionic liquid moieties as a simple, scalable prodrug
platform for treating skin disease.
AB - The high prevalence of skin diseases and their visible symptoms result in major
physical, emotional, and economic burden for which few solutions exist. To
address this unmet medical need, topical delivery of RNAi such as siRNA holds
many advantages including direct access to the diseased site, potent knockdown of
disease symptoms, and limited off-target effects. Unfortunately, delivering drugs
into skin is extremely difficult. To address these concerns, we present RNAi
robed with ionic liquid moieties. Specifically, we show that robed-siRNAs can be
synthesized by a simple two-step process from bulk materials. Robing affords
tuneability of properties necessary for dermal drug delivery including octanol
water partitioning, skin transport, and cell internalization. The efficacy and
safety of robed-siRNA for treating skin disease was confirmed by its ability to
limit breakdown of elastin, a major cause of premature aging, following UVB
exposure to human reconstructed skin tissue. Together, the data strongly support
that therapeutic RNAi robed with ionic liquid moieties are a simple, scalable
prodrug platform for treating skin disease.
PMID- 27612408
TI - In vitro models for evaluating safety and efficacy of novel technologies for skin
drug delivery.
AB - For preclinical testing of novel therapeutics, predictive in vitro models of the
human skin are required to assess efficacy, absorption and safety. Simple as well
as more sophisticated three-dimensional organotypic models of the human skin
emerged as versatile and powerful tools simulating healthy as well as diseased
skin states. Besides addressing the demands of research and industry, such models
serve as valid alternative to animal testing. Recently, the acceptance of several
models by regulatory authorities corroborates their role as important building
block for preclinical development. However, valid assessment of readout
parameters derived from these models requires suitable analytical techniques.
Standard analytical methods are mostly destructive and limited regarding in-depth
investigation on molecular level. The combination of adequate in vitro models
with modern non-invasive analytical modalities bears a great potential to address
important skin drug delivery related questions. Topics of interest are for
instance the assessment of repeated dosing effects and xenobiotic
biotransformation, which cannot be analyzed by destructive techniques. This
review provides a comprehensive overview of current in vitro skin models
differing in functional complexity and mimicking healthy as well as diseased skin
states. Further, benefits and limitations regarding analytical evaluation of
efficacy, absorption and safety of novel drug carrier systems applied to such
models are discussed along with a prospective view of anticipated future
directions. In addition, emerging non-invasive imaging modalities are introduced
and their significance and potential to advance current knowledge in the field of
skin drug delivery is explored.
PMID- 27612409
TI - Galectin-1 circumvents lysolecithin-induced demyelination through the modulation
of microglial polarization/phagocytosis and oligodendroglial differentiation.
AB - Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins,
binds to the common disaccharide [Galbeta(1-4)-GlcNAc] on both N- and O-glycans
decorating cell surface glycoconjugates. Current evidence supports a role for Gal
1 in the pathophysiology of multiple sclerosis (MS), one of the most prevalent
chronic inflammatory diseases. Previous studies showed that Gal-1 exerts
neuroprotective effects by promoting microglial deactivation in a model of
autoimmune neuroinflammation and induces axonal regeneration in spinal cord
injury. Seeking a model that could link demyelination, oligodendrocyte (OLG)
responses and microglial activation, here we used a lysolecithin (LPC)-induced
demyelination model to evaluate the ability of Gal-1 to preserve myelin without
taking part in T-cell modulation. Gal-1 treatment after LPC-induced demyelination
promoted a significant decrease in the demyelinated area and fostered more
efficient remyelination, concomitantly with an attenuated oligodendroglial
progenitor response reflecting less severe myelination damage. These results were
accompanied by a decrease in the area of microglial activation with a shift
toward an M2-polarized microglial phenotype and diminished astroglial activation.
In vitro studies further showed that, mechanistically, Gal-1 targets activated
microglia, promoting an increase in their myelin phagocytic capacity and their
shift toward an M2 phenotype, and leads to oligodendroglial differentiation.
Therefore, this study supports the use of Gal-1 as a potential treatment for
demyelinating diseases such as MS.
PMID- 27612410
TI - Genome-wide association study on the FEV1/FVC ratio in never-smokers identifies
HHIP and FAM13A.
AB - BACKGROUND: Although a striking proportion (25% to 45%) of patients with chronic
obstructive pulmonary disease are never-smokers, most genetic susceptibility
studies have not focused on this group exclusively. OBJECTIVE: The aim of this
study was to identify common genetic variants associated with FEV1 and its ratio
to forced vital capacity (FVC) in never-smokers. METHODS: Genome-wide association
studies were performed in 5070 never-smokers of the identification cohort
LifeLines, and results (P < 10-5) were verified by using a meta-analysis of the
Vlagtwedde-Vlaardingen study and the Rotterdam Study I-III (total n = 1966).
Furthermore, we aimed to assess the effects of the replicated variants in more
detail by performing genetic risk score, expression quantitative trait loci, and
variant*ever-smoking interaction analyses. RESULTS: We identified associations
between the FEV1/FVC ratio and 5 common genetic variants in the identification
cohort, and 2 of these associations were replicated. The 2 variants annotated to
the genes hedgehog interacting protein (HHIP) and family with sequence similarity
13 member A (FAM13A) were shown to have an additive effect on FEV1/FVC levels in
the genetic risk score analysis; were associated with gene expression of HHIP and
FAM13A in lung tissue, respectively; and were genome-wide significant in a meta
analysis including both identification and 4 verification cohorts (P < 2.19 * 10
7). Finally, we did not identify significant interactions between the variants
and ever smoking. Results of the FEV1 identification analysis were not
replicated. CONCLUSION: The genes HHIP and FAM13A confer a risk for airway
obstruction in general that is not driven exclusively by cigarette smoking, which
is the main risk factor for chronic obstructive pulmonary disease.
PMID- 27612411
TI - Symptoms, signs and radiologic findings in patients having reoperative surgery
for malignant peritoneal mesothelioma.
AB - BACKGROUND: A reasonable estimate is that 50% of patients treated with
cytoreductive surgery (CRS) and perioperative chemotherapy for malignant
peritoneal mesothelioma will recur. Recognition of this recurrence and
knowledgeable selection for additional surgical intervention is important in
improving survival of patients who progress. MATERIAL AND METHODS: Patients
treated for malignant peritoneal mesothelioma with CRS and perioperative
chemotherapy were placed in follow-up for assessment of symptoms and signs and
radiologic abnormalities by CT. The data were prospectively maintained and
retrospectively reviewed. RESULTS: From a database of 130 patients with malignant
peritoneal mesothelioma, 38 patients who had 50 reoperations with disease
recurrence that was histologically confirmed were studied. The median time to
first recurrence was 14 months with a range of 3-102. Considering 50 reoperative
events the most common symptoms or signs were abdominal pain (40%) and abdominal
distention (34%). The most common radiologic finding was a tumor mass (56%).
Patients with an abdominal or pelvic mass had a reduced prognosis (p = 0.006) and
patients with an absence of radiologic abnormalities had an improved survival (p
= 0.047). CONCLUSIONS: In patients having reoperative surgery, symptoms, signs
and radiologic abnormalities associated with recurrent (progressive) malignant
peritoneal mesothelioma are abdominal pain, abdominal distention, and a tumor
mass. An abdominal or pelvic mass was associated with a reduced prognosis and an
absence of radiologic abnormalities with an improved prognosis.
PMID- 27612412
TI - A systematic review and meta-analysis of oncological and renal function outcomes
obtained after segmental ureterectomy versus radical nephroureterectomy for upper
tract urothelial carcinoma.
AB - OBJECTIVE: To perform a systematic review and meta-analysis of the comparative
studies reporting oncological and renal function outcomes of segmental
ureterectomy (SU) versus radical nephroureterectomy (RNU) for upper tract
urothelial carcinomas (UTUC). MATERIALS AND METHODS: A literature search on
Pubmed, Embase, and the Cochrane library was conducted according to the PRISMA
guidelines, and a meta-analysis was performed to assess cancer-specific survival
(CSS), overall survival (OS), recurrence-free survival (RFS), intravesical
recurrence free survival (IVRFS) and surgery-related variations in estimated
glomerular filtration rate (eGFR). RESULTS: A total of 11 retrospective studies
with 3963 patients who underwent either SU (n = 983; 24.8%) or RNU (n = 2980;
75.2%) were included. Although patients treated with SU were more likely to be
diagnosed with favorable pathological features, the meta-analysis of unadjusted
data revealed no significant difference between both groups in terms of CSS (HR
0.90, p = 0.33) and OS (HR 0.98, p = 0.93). Accordingly, the meta-analysis of
adjusted data confirmed equivalent CSS (HR = 0.90, p = 0.47) between SU and RNU.
Similarly, no significant difference was found in terms of RFS (HR 1.06, p =
0.72) and IVRFS (HR 1.35, p = 0.39). However, a significant decreased risk of
impaired renal function was observed after SU when compared to RNU (mean eGFR
difference = 9.32 ml/1.73 m2, p = 0.007). CONCLUSION: Although adverse patient
and tumor characteristics were not equally balanced between treatment arms, our
systematic review and meta-analysis supports similar oncological outcomes between
SU and RNU, with better preservation of renal function after SU. As such, SU
should be preferably used as the first-line treatment for low-risk ureter tumors,
while considered for selected cases of high-risk disease.
PMID- 27612413
TI - Robotic single site staging in endometrial cancer: A multi-institution study.
AB - OBJECTIVE: To evaluate the feasibility and the safety of robotic single site
hysterectomy (RSSH) plus or less pelvic lymphadenectomy in FIGO stage I-II
endometrial cancer. MATERIALS AND METHODS: We prospectively collected patient
demographics, operative times, complications, pathologic results, and length of
stay on all patients who underwent RSSH plus or less pelvic lymphadenectomy for
clinical FIGO stage I or occult stage II endometrial carcinoma. RESULTS: From
January 2012 to February 2015, 125 patients were included in our study. The
median age of the patients was 59 years (range, 35-84 years) and the median body
mass index was 27 kg/m(2) (range, 19-52 kg/m(2)). One patient was converted to
vaginal surgery due to problems of hypercapnia. The median docking time, console
time, and total operative time was 11 min (range, 4-40 min), 80 min (range, 20
240 min) and 122 min (range, 35-282 min), respectively. The median blood loss was
50 ml (range, 10-250 ml). No laparoscopic/laparotomic conversion was registered.
Twenty one patients underwent pelvic lymphadenectomy (16.8%) and the median
pelvic lymph nodes was 13 (range, 3-32). The median time to discharge was 2 days
(range, 1-3 days). No intra-operative complications occurred, while we observed
10 (8%) early post-operative complications. CONCLUSION: RSSH plus or less pelvic
lymphadenectomy is technically feasible, safe and reproducible and could be the
treatment of choice for patients affected by FIGO stage I-II endometrial cancer.
However, randomized controlled trials are needed to confirm these results.
PMID- 27612414
TI - An Innovative Approach to the Repair of Distal Tibia Nonunion Using a Retrograde
Buried Tibio-Talar-Calcaneal Nail: A Case Report.
AB - We report a case using retrograde tibial nailing as treatment of nonunion of a
distal tibial osteotomy, which was performed as part of a complex reconstruction
of distal tibial malunion with ankle arthritis. Although retrograde nailing has
classically been used for tibial-talar-calcaneal arthrodesis, this method spares
the subtalar joint. Preservation of some hindfoot motion by subtalar mobility
allows for a decrease in the loss of function typically seen with tibial-talar
calcaneal arthrodesis.
PMID- 27612415
TI - Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears.
AB - Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities
and Guillain-Barre syndrome. ZIKV infection also results in severe eye disease
characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns
and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye
by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice
developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic
nerve, and ganglion and bipolar cells in the retina. This phenotype was
independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-),
and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar
to those of control animals. We also detected abundant viral RNA in tears,
suggesting that virus might be secreted from lacrimal glands or shed from the
cornea. This model provides a foundation for studying ZIKV-induced ocular
disease, defining mechanisms of viral persistence, and developing therapeutic
approaches for viral infections of the eye.
PMID- 27612416
TI - Determining witnessed status for out-of-hospital cardiac arrest.
AB - OBJECTIVE: Witnessed status is considered a core variable in reporting cardiac
arrest data and can be ascertained from either the emergency dispatch recording
or the pre-hospital record. The purpose of this study is to compare and assess
the quality and consistency of these information sources. METHODS: This
retrospective analysis included 1896 cases of out-of-hospital cardiac arrest
occurring between September 1, 2012 and December 31, 2014. RESULTS: We found that
there was minimal (kappa=0.30, 95% CI 0.27-0.33) to moderate (kappa=0.64, 95% CI
0.59-0.69) agreement between the pre-hospital record and the emergency dispatch
recording when these sources of information are used to determine witnessed
status. Witnessed status could not be determined from the emergency dispatch
recording in 36.2% (n=684) of eligible cases. Survival was similar regardless of
the method used to determine witnessed status. Using a combination of the pre
hospital record and the emergency dispatch recording yielded the highest number
of witnessed cases. CONCLUSION: The determination of witnessed status in out-of
hospital cardiac arrest may be challenging, as evidenced by the discrepancies in
witnessed status when comparing different sources of information. The large
number of cases where the witnessed status could not be determined from the
emergency dispatch recording precludes its use as the sole source of information.
It is reasonable to use the patient care record alone, however it should be
recognized that there is misclassification of witnessed status regardless of the
method used and this may affect the strength of association between witnessed
status and survival.
PMID- 27612417
TI - A three-molecule score based on Notch pathway predicts poor prognosis in non
metastasis clear cell renal cell carcinoma.
AB - We constructed a three-molecule score based on the expression of Notch pathway
molecules: Jagged1, intracellular Notch1 (ICN1) and Hes1 (JIH score). To assess
prognostic value of the JIH score in non-metastasis clear cell renal cell
carcinoma (ccRCC), we identified 467 patients who underwent nephrectomy during
2008-2009 as our study population. Immunohistochemistry was used to evaluate the
expression of these three molecules. Cox regression models were applied to
construct the JIH score, while Kaplan-Meier methods, multivariate analyses and
nomogram were used to explore prognostic value of the JIH score. Our result
confirmed that JIH score was an independent prognosticator for both overall
survival (OS) and recurrence-free survival (RFS). Survival analyses showed that a
higher JIH score indicated worse clinical outcomes (JIH score 3: 58.3% and 58.0%
for 6-year OS and RFS, respectively; JIH score 0: 96.7% and 91.6% for 6-year OS
and RFS, respectively). Nomograms based on JIH score and other conventional
clinicopathological features had a better capability in predicting patients with
pT1 stage disease for both OS and RFS (84.6% and 83.9%, respectively). The JIH
score is a novel prognosticator representing activation of Notch pathway for non
metastasis ccRCC, and raises an alternative strategy for excavating potential
biomarkers for signal pathways.
PMID- 27612418
TI - Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor
initiation in a colon cancer preclinical model.
AB - Inheritance of a gene mutation leads to the initiation of 5 to 10% of most
cancers, including colon cancer cases. We developed a chemoprevention strategy
using a novel combination of the non-steroidal anti-inflammatory (NSAID) sulindac
plus the anthelminthic benzimidazole, mebendazole. This oral drug combination was
effective in the ApcMin/+ mouse model of Familial Adenomatous Polyposis (FAP).
Treatment with 35 mg/kg daily mebendazole reduced the number of intestinal
adenomas by 56% (P = 0.0002), 160 ppm sulindac by 74% (P < 0.0001), and the
combination by 90% (P < 0.0001). The combination significantly reduced
microadenomas, polyp number and size in both the small intestines and colon when
compared to untreated controls or sulindac alone. Mebendazole as a single agent
decreased COX2 expression, blood vessel formation, VEGFR2 phosphorylation, and
worked synergistically with sulindac to reduce overexpression of MYC, BCL2, and
various pro-inflammatory cytokines. Given the low toxicity of mebendazole, these
preclinical findings support the consideration of clinical trials for high risk
cancer patients using mebendazole either alone or in combination. The findings
have implications for populations with moderate and above risk for developing
cancer.
PMID- 27612419
TI - nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in
thyroid cancer.
AB - nc886 is a recently identified cellular non-coding RNA and its depletion leads to
acute cell death via PKR (Protein Kinase RNA-activated) activation. nc886
expression is increased in some malignancies, but silenced in others. However,
the precise role of nc886/PKR is controversial: is it a tumor suppressor or an
oncogene? In this study, we have clarified the role of nc886 in thyroid cancer by
sequentially generating PKR knockout (KO) and PKR/nc886 double KO cell lines from
Nthy-ori 3-1, a partially transformed thyroid cell line. Compared to the
wildtype, PKR KO alone does not exhibit any significant phenotypic changes.
However, nc886 KO cells are less proliferative, migratory, and invasive than
their parental PKR KO cells. Importantly, the requirement of nc886 in tumor
phenotypes is totally independent of PKR. In our microarray data, nc886 KO
suppresses some genes whose elevated expression is associated with poor survival
confirmed by data from total of 505 thyroid cancer patients in the Caner Genome
Atlas project. Also, the nc886 expression level tends to be elevated and in more
aggressively metastatic tumor specimens from thyroid cancer patients. In summary,
we have discovered nc886's tumor-promoting role in thyroid cancer which has been
concealed by the PKR-mediated acute cell death.
PMID- 27612420
TI - ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA
replication.
AB - ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator
harboring an AAA+ ATPase domain and a bromodomain, previously proposed to
function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is
also required for DNA replication. ATAD2 is co-expressed with genes involved in
DNA replication in various cancer types and predominantly expressed in S phase
cells where it localized on nascent chromatin (replication sites). Our extensive
biochemical and cellular analyses revealed that ATAD2 is recruited to replication
sites through a direct interaction with di-acetylated histone H4 at K5 and K12,
indicative of newly synthesized histones during replication-coupled chromatin
reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that
are deficient in binding to these di-acetylation marks resulted in reduced DNA
replication and impaired loading of PCNA onto chromatin, suggesting relevance of
ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2
in cancer and for the first time identify a reader of newly synthesized histone
di-acetylation-marks during replication.
PMID- 27612421
TI - Pathologic heterogeneity of lung adenocarcinomas: A novel pathologic index
predicts survival.
AB - Although the most predominant subtype of invasive lung adenocarcinoma has been
reported to have clinical significance, a major limitation of this concept is
that most tumors are mixed-subtype. Therefore, we aimed to determine the
individual prognostic significance of each subtype and also attempted to
establish a pathologic index that reflects the pathologic subtypes and overall
heterogeneity of lung adenocarcinomas and evaluated its prognostic significance.
The individual prognostic impact of each subtype was assessed from the
development cohort using the disease-free survival (DFS) curve of a previous
large-scale study. Hazard ratios (HRs) from the development cohort were 1, 1.025,
1.059, 1.495, and 1.160 for the lepidic, acinar, papillary, micropapillary, and
solid pattern subtype, respectively. Based on the calculated HR of each subtype,
four indices representing pathologic heterogeneity were developed. The first and
second indices were defined as the sum of the proportions of each subtype
multiplied by their HRs, with the addition of either entropy or Gini coefficient,
respectively. The third index was calculated as the sum of all subtype
percentages multiplied by their HRs. To emphasize heterogeneity, the fourth index
was defined as the simple arithmetic sum of the scores of the subtypes multiplied
by their HRs. Each subtype was assigned a score of 0 if the subtype was absent
and a score of 1 if the subtype was present in a binary fashion. We applied these
four pathologic indices to a validation group of 148 patients with comprehensive
histologic subtyping for completely resected lung adenocarcinomas. DFS curves
were plotted and predictive ability of each pathologic index was evaluated. Among
the four pathologic indices, only pathologic index 3 enabled significant patient
stratification in the validation cohort according to DFS (P = 0.004) and showed
the highest Harrell's C index of 0.691 of all four pathologic indices. In
conclusion, we estimated the HR of each subtype and generated four pathologic
indices that reflect heterogeneity. One of these, index 3, the pathologic
heterogeneity index based on the sum of all subtype percentages multiplied by
their HR, possesses good prognostic ability for predicting survival in patients
with lung adenocarcinoma.
PMID- 27612422
TI - Temozolomide toxicity operates in a xCT/SLC7a11 dependent manner and is fostered
by ferroptosis.
AB - The glutamate exchanger xCT (SLC7a11) is causally linked with the malignancy
grade of brain tumors and represents a key player in glutamate, cystine and
glutathione metabolism. Although blocking xCT is not cytotoxic for brain tumors,
xCT inhibition disrupts the neurodegenerative and microenvironment-toxifying
activity of gliomas. Here, we report on the use of various xCT inhibitors as
single modal drugs and in combination with the autophagy-inducing standard
chemotherapeutic agent temozolomide (Temodal/Temcad(r), TMZ). xCT overexpressing
cells (xCTOE) are more resistant to the FDA and EMA approved drug sulfasalazine
(Azulfidine/Salazopyrin/Sulazine(r), SAS) and RNAi-mediated xCT knock down
(xCTKD) in gliomas increases the susceptibility towards SAS in rodent gliomas. In
human gliomas, challenged xCT expression had no impact on SAS-induced
cytotoxicity. Noteworthy, other xCT inhibitors such as erastin and sorafenib
showed enhanced efficacy on xCTKD gliomas. In contrast, cytotoxic action of TMZ
operates independently from xCT expression levels on rodent gliomas. Human glioma
cells with silenced xCT expression display higher vulnerability towards TMZ alone
as well as towards combined TMZ and SAS. Hence, we tested the partial xCT
blockers and ferroptosis inducing agents erastin and sorafenib (Nexavar(r), FDA
and EMA-approved drug for lung cancer). Noteworthy, xCTOE gliomas withstand
erastin and sorafenib-induced cell death in a concentration-dependent manner,
whereas siRNA-mediated xCT knock down increased susceptibility towards erastin
and sorafenib. TMZ efficacy can be potentiated when combined with erastin,
however not by sorafenib. Moreover, gliomas with high xCT expression are more
vulnerable towards combinatorial treatment with erastin-temozolomide. These
results disclose that ferroptosis inducers are valid compounds for potentiating
the frontline therapeutic agent temozolomide in a multitoxic approach.
PMID- 27612423
TI - Differential protein stability of EGFR mutants determines responsiveness to
tyrosine kinase inhibitors.
AB - Non-small cell lung cancer (NSCLC) patients carrying specific EGFR kinase
activating mutations (L858R, delE746-A750) respond well to tyrosine kinase
inhibitors (TKIs). However, drug resistance develops within a year. In about 50%
of such patients, acquired drug resistance is attributed to the enrichment of a
constitutively active point mutation within the EGFR kinase domain (T790M). To
date, differential drug-binding and altered ATP affinities by EGFR mutants have
been shown to be responsible for differential TKI response. As it has been
reported that EGFR stability plays a role in the survival of EGFR driven cancers,
we hypothesized that differential TKI-induced receptor degradation between the
sensitive L858R and delE746-A750 and the resistant T790M may also play a role in
drug responsiveness. To explore this, we have utilized an EGFR-null CHO
overexpression system as well as NSCLC cell lines expressing various EGFR mutants
and determined the effects of erlotinib treatment. We found that erlotinib
inhibits EGFR phosphorylation in both TKI sensitive and resistant cells, but the
protein half-lives of L858R and delE746-A750 were significantly shorter than
L858R/T790M. Third generation EGFR kinase inhibitor (AZD9291) inhibits the growth
of L858R/T790M-EGFR driven cells and also induces EGFR degradation. Erlotinib
treatment induced polyubiquitination and proteasomal degradation, primarily in a
c-CBL-independent manner, in TKI sensitive L858R and delE746-A750 mutants when
compared to the L858R/T790M mutant, which correlated with drug sensitivity. These
data suggest an additional mechanism of TKI resistance, and we postulate that
agents that degrade L858R/T790M-EGFR protein may overcome TKI resistance.
PMID- 27612424
TI - Low expression of miR-381 is a favorite prognosis factor and enhances the
chemosensitivity of osteosarcoma.
AB - Osteosarcoma (OS) is the most common primary bone malignancy with a poor
prognosis for all races and both sexes. In this study, we found that miR-381 is a
positive prognosis factor for OS patients that OS patients with a low expression
of miR-381 had a longer survival time after surgical intervention, and miR-381
expression promotes MG-63 cell proliferation and cell invasion ability. Our
results also showed a strong negative correlation between the expression of miR
381 and LRRC4 (brain relative specific expression gene) in OS tissues. This
demonstrated that LRRC4 is a direct target gene of miR-381, and suppressing the
expression of miR-381 increases the sensitivity of OS cells to chemotherapeutic
drugs through the LRRC4-mediated mTOR pathway. In summary, miR-381 is an
important biomarker in directing therapeutic intervention and predicting
prognosis in OS patients.
PMID- 27612425
TI - The somatic POLE P286R mutation defines a unique subclass of colorectal cancer
featuring hypermutation, representing a potential genomic biomarker for
immunotherapy.
AB - Early-onset colorectal cancers (EOCRCs) may have biological or genomic features
distinct from late-onset CRCs (LOCRCs). Previous studies have mostly focused on
the germline predisposition conditions of EOCRCs, but we hypothesized that EOCRCs
may have distinct somatic aberrations that accelerate cancer development. To
identify the somatic aberrations that accelerate cancer development at an early
age, we conducted whole exome sequencing for 28 polyposis-unrelated,
microsatellite stable (MSS) EOCRCs with no known germline predisposition
conditions. Surprisingly, we found two distinct groups in the context of
mutational burden: 6 hypermutated cases with 2325 to 10973 mutations and 22
nonhypermutated cases with 47 to 154 mutations. Further analysis revealed that
four of the six hypermutated cases had the same POLE P286R mutation. We validated
this finding in 83 MSS EOCRCs and 27 MSS LOCRCs, which revealed that 7.2% of
EOCRCs (6/83) had the POLE P286R mutation, which was not found in LOCRCs.
Clinicopathologically, EOCRCs with POLE mutations occurred far more frequently in
the right colon than in the left colon, affecting men more frequently than women.
In summary, we have identified a unique subclass of colon cancer characterized by
a hypermutation associated with the POLE mutation. The acquisition of the POLE
mutation leading to hypermutation can accelerate cancer development. Clinically,
this subset with hypermutation may be susceptible to immune checkpoint blockade.
PMID- 27612426
TI - Inhibition of nuclear factor-kappaB signaling suppresses Spint1-deletion-induced
tumor susceptibility in the ApcMin/+ model.
AB - Hepatocyte growth factor activator inhibitor type 1 (HAI-1), encoded by the
Spint1 gene, is a membrane-bound serine protease inhibitor expressed on the
epithelial cell surface. We have previously reported that the intestine-specific
Spint1-deleted ApcMin/+ mice showed accelerated formation of intestinal tumors.
In this study, we focused on the role of nuclear factor-kappaB (NF-kappaB)
signaling in the HAI-1 loss-induced tumor susceptibility. In the HAI-1-deficient
intestine, inflammatory cytokines, such as tumor necrosis factor-alpha and
interleukin-6, were upregulated in normal mucosa. Furthermore, increased nuclear
translocation of NF-kappaB was observed in both normal mucosa and tumor tissues
of HAI-1-deficient ApcMin/+ intestines, and an NF-kappaB target gene, such as
urokinase-type plasminogen activator, was upregulated in the HAI-1-deficient
tumor tissues. Thus, we investigated the effect of dehydroxymethylepoxyquinomicin
(DHMEQ), a synthetic inhibitor of NF-kappaB, on intestinal HAI-1-deficient
ApcMin/+ mice. Treatment with DHMEQ reduced the formation of intestinal tumors
compared with vehicle control in the HAI-1-deficient ApcMin/+ mice. These results
suggested that insufficient HAI-1 function promotes intestinal carcinogenesis by
activating NF-kappaB signaling.
PMID- 27612427
TI - DCTPP1 attenuates the sensitivity of human gastric cancer cells to 5-fluorouracil
by up-regulating MDR1 expression epigenetically.
AB - Gastric cancer (GC) is among the most malignant cancers with high incidence and
poor prognoses worldwide as well as in China. dCTP pyrophosphatase 1 (DCTPP1) is
overexpressed in GC with a poor prognosis. Given chemotherapeutic drugs share
similar structures with pyrimidine nucleotides, the role of DCTPP1 in affecting
the drug sensitivity in GC remains unclear and is worthy of investigation. In the
present study, we reported that DCTPP1-knockdown GC cell line BGC-823 exhibited
more sensitivity to 5-fluorouracil (5-FU), demonstrated by the retardation of
cell proliferation, the increase in cell apoptosis, cell cycle arrest at S phase
and more DNA damages. Multidrug resistance 1 (MDR1) expression was unexpectedly
down-regulated in DCTPP1-knockdown BGC-823 cells together with more intracellular
5-FU accumulation. This was in large achieved by the elevated methylation in
promoter region of MDR1 gene. The intracellular 5-methyl-dCTP level increased in
DCTPP1-knockdown BGC-823 cells as well. More significantly, the strong
correlation of DCTPP1 and MDR1 expression was detectable in clinical GC samples.
Our results thus imply a novel mechanism of chemoresistance mediated by the
overexpression of DCTPP1 in GC. It is achieved partially through decreasing the
concentration of intracellular 5-methyl-dCTP, which in turn results in promoter
hypomethylation and hyper-expression of drug resistant gene MDR1. Our study
suggests DCTPP1 as a potential indicative biomarker for the predication of
chemoresistance in GC.
PMID- 27612428
TI - Low-dose salinomycin induces anti-leukemic responses in AML and MLL.
AB - Development of anti-cancer drugs towards clinical application is costly and
inefficient. Large screens of drugs, efficacious for non-cancer disease, are
currently being used to identify candidates for repurposing based on their anti
cancer properties. Here, we show that low-dose salinomycin, a coccidiostat
ionophore previously identified in a breast cancer screen, has anti-leukemic
efficacy. AML and MLLr cell lines, primary cells and patient samples were
sensitive to submicromolar salinomycin. Most strikingly, colony formation of
normal hematopoietic cells was unaffected by salinomycin, demonstrating a lack of
hemotoxicity at the effective concentrations. Furthermore, salinomycin treatment
of primary cells resulted in loss of leukemia repopulation ability following
transplantation, as demonstrated by extended recipient survival compared to
controls. Bioinformatic analysis of a 17-gene signature identified and validated
in primary MLLr cells, uncovered immunomodulatory pathways, hubs and protein
interactions as potential transducers of low dose salinomycin treatment.
Additionally, increased protein expression of p62/Sqstm1, encoded for by one of
the 17 signature genes, demonstrates a role for salinomycin in aggresome/vesicle
formation indicative of an autophagic response.Together, the data support the
efficacy of salinomycin as an anti-leukemic at non-hemotoxic concentrations.
Further investigation alone or in combination with other therapies is warranted
for future clinical trial.
PMID- 27612429
TI - EPRS is a critical regulator of cell proliferation and estrogen signaling in ER+
breast cancer.
AB - Aminoacyl tRNA synthetases (ARSs) are a class of enzymes with well-conserved
housekeeping functions in cellular translation. Recent evidence suggests that ARS
genes may participate in a wide array of cellular processes, and may contribute
to the pathology of autoimmune disease, cancer, and other diseases. Several
studies have suggested a role for the glutamyl prolyl tRNA synthetase (EPRS) in
breast cancers, although none has identified any underlying mechanism about how
EPRS contributes to carcinogenesis. In this study, we identified EPRS as
upregulated in estrogen receptor positive (ER+) human breast tumors in the TCGA
and METABRIC cohorts, with copy number gains in nearly 50% of samples in both
datasets. EPRS expression is associated with reduced overall survival in patients
with ER+ tumors in TCGA and METABRIC datasets. EPRS expression was also
associated with reduced distant relapse-free survival in patients treated with
adjuvant tamoxifen monotherapy for five years, and EPRS-correlated genes were
highly enriched for genes predictive of a poor response to tamoxifen. We
demonstrated the necessity of EPRS for proliferation of tamoxifen-resistant ER+
breast cancer, but not ER- breast cancer cells. Transcriptomic profiling showed
that EPRS regulated cell cycle and estrogen response genes. Finally, we
constructed a causal gene network based on over 2500 ER+ breast tumor samples to
build up an EPRS-estrogen signaling pathway. EPRS and its regulated estrogenic
gene network may offer a promising alternative approach to target ER+ breast
cancers that are refractory to current anti-estrogens.
PMID- 27612431
TI - Onychomycosis in children. A review.
AB - Onychomycosis is considered an age-related infection with increasing prevalence
in the older age groups. It is rare in the pediatric population, except in
children with Down syndrome and with immunodeficiencies, who are more likely to
have fungal nail infections. The number of reports about onychomycosis in
children is relatively small, and the epidemiologic data vary, but a rise in
prevalence has been demonstrated. In this article, we review the most up-to-date
literature and summarize the epidemiology, etiology, clinical presentation,
diagnosis, and treatment of onychomycosis in children, as well as the differences
with the disease presenting in adults. Dermatologists must consider onychomycosis
in the differential diagnosis of nail alterations in children and always perform
a mycological study to confirm the diagnosis.
PMID- 27612430
TI - Restoring miR122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy
through Smad-independent TGF-beta pathway.
AB - miR122 is the prevalent miRNA in adult healthy liver and it is responsible for
liver stem cell differentiation towards hepatocyte lineage. Its expression is
frequently lost in hepatocellular carcinoma (HCC). We studied the effects of
restoring miR122 expression in a distinctive cell line derived from human HCC
BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability
and undetectable miR122 expression. We generated a stable BCLC9 cell line that
expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases
cell proliferation rate and reduces significantly tumor size in vivo. BCLC9
miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes
and up-regulate FOXO1 and FOXO3A gene expression. In addition, miR122 transfected
cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein
inactivation. Reduction in tumor size in BCLC9-miR122 associated with an increase
in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to
phospho-p38 ratio. Treatment of miR122 positive cells with an inhibitor of TGFBR1
activation, abolished tumor dormancy program and recovered cell proliferation
rate through a Smad-independent TGF-beta response.HCC stem-like cells can be
directed towards cell differentiation and tumor dormancy by restoring miR122
expression. We demonstrate, for the first time, that dormancy program is achieved
through a Smad-independent TGF-beta pathway. Restablishing miR122 expression is a
promising therapeutic strategy that would work concurrently reducing tumor
aggressiveness and decreasing disease recurrence.
PMID- 27612432
TI - Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by
restoring the dysfunction of the neurotransmitter systems in the rat model of
Alzheimer's disease.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A.Mey. is a traditional Chinese
herbal medicine, which has been used to treat Alzheimer's disease (AD) for
thousands of years. Ginsenoside is one of the major compounds found in P.
ginseng. This study aimed to explore the attenuation of spatial memory impairment
by ginsenosides and its correlation with restoring the dysfunction of the
neurotransmitter systems in AD model rats to understand the mechanism underlying
the anti-AD effect of P. ginseng. MATERIALS AND METHODS: In this study, the AD
model was established by combining d-galactose (d-gal) with AlCl3 (Al) for 60
days. From day 30, the ginsenosides group was intragastrically administered with
ginsenosides for 30 days. The ethology of rats was tested through the Morris
water maze test(MWM). Histopathological changes in the hippocampus of rats were
observed through hematoxylin and eosin staining. The expressions of amyloid beta
peptide (Abeta) and phospho-tau (p-tau) in the hippocampus and cortex of rats
were detected by immunohistochemistry. A liquid chromatography-mass spectrometry
assay was used to measure neurotransmitter concentrations in the hippocampus,
cortex, and blood. RESULTS: Ginsenosides could significantly decrease the escape
latency time and the average latency time in the place navigation test and
increase the times of crossing the platform area, the percentage of residence
time, and the distance in the original platform quadrant in the spatial probe
test. Ginsenosides could repair the damage of the hippocampus and reduce the
expressions of Abeta and p-tau. Ginsenosides could also increase gamma
aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and
aspartic acid levels in the hippocampus and cortex and increase glycine and
serotonin levels in the blood. CONCLUSIONS: After effectively administrated,
ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The
possible mechanism of the beneficial effect is restoring the dysfunction of
various neurotransmitters.
PMID- 27612434
TI - Plant materials for gastrointestinal diseases used in Chawang District, Nakhon Si
Thammarat Province, Thailand.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: In Thailand, gastrointestinal diseases have
occurred since the past, consequently healers know well how to use herbs for
treatment. Currently, some groups of Thai people continue to be interested in
treating diseases by herbs. Therefore, the aims of this study were to (1) compile
a list of species of medicinal plants and their source, (2) document the diseases
treated and their frequency of citation, (3) record the parts used, methods of
preparation and route of administration of traditional medicines, and (4) compare
the folk knowledge to that in other relevant reports. MATERIALS AND METHODS: Ten
folk healers were included in the study. Semi-structured interviews were used to
compile data, namely plant parts used, preparation, route of administration and
properties. The data were analyzed by interpretation and descriptive statistics.
RESULTS: Sixty-two species in 28 families were identified. The most used plants
(11 species) were grouped in Zingiberaceae. The highest level of relative
frequency of citation (RFC) was found in Zingiber officinale Roscoe (1.0). Most
plants were applied for treating constipation. Powder was the most common
preparation form of folk drug. A total of 174 use lists were recorded, however,
more than two thirds were reported as new uses in this study. CONCLUSION: A
literature review revealed that the remaining 37 species for pharmacological
activities and 42 species for toxicity should be further studied to validate the
folk use of these medicinal resource.
PMID- 27612433
TI - Anti-inflammatory, antioxidant and anti-Mycobacterium tuberculosis activity of
viridiflorol: The major constituent of Allophylus edulis (A. St.-Hil., A. Juss. &
Cambess.) Radlk.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Allophylus edulis (A. St.-Hil., A.
Juss. & Cambess.) Radlk. (Sapindaceae) are traditionally used as a natural anti
inflammatory agent; however, there are no scientific studies demonstrating its
activity essential oil. The content of essential oil in A. edulis may be the
chemical basis to explain its ethnobotanical uses, since infusions of this plant
are used to treat inflammation in the traditional medicine in Brazil. AIM OF THE
STUDY: This study evaluated the anti-inflammatory, antioxidant and anti
mycobacterial activities of the essential oil (EOAE) and viridiflorol, its main
compound. MATERIAL AND METHODS: Essential oil from fresh leaves of A. edulis
(EOAE) was obtained by hydrodistillation in a Clevenger-type apparatus. Forty-one
compounds, accounting for 99.10% of the oil, were identified by gas
chromatography-mass spectrometry (GC-MS). The major constituent of the oil was
viridiflorol (30.88%). Additionally, the essential oil and viridiflorol were
evaluated using an in vitro test against Mycobacterium tuberculosis and in 2,2
diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) (ABTS) assays. Both EOAE (30 and 100mg/kg) and viridiflorol (3
and 30mg/kg) by oral administration were assayed in carrageenan-induced mice paw
oedema and pleurisy using subcutaneous injection of dexamethasone (0.5mg/kg) as
the positive control. RESULTS: EOAE and viridiflorol displayed moderate in vitro
activity in the M. tuberculosis assay. In all tests, EOAE and viridiflorol showed
moderate antioxidant activity compared with reference standards. Both EOAE and
viridiflorol showed significant inhibition in the carrageenan-induced mice paw
oedema via oral administration of the oil (30 and 100mg/kg), compound (3 and
30mg/kg), and subcutaneous injection of dexamethasone (0.5mg/kg, reference drug).
Also EOAE and viridiflorol significantly inhibited carrageenan (Cg) induced
pleurisy, reducing the migration of total leucocytes in mice by 62+/-5% (30mg/kg
of oil), 35+/-8% (100mg/kg of oil), 71+/-5% (3mg/kg of viridiflorol) and 57+/-3%
(30mg/kg of viridiflorol). CONCLUSION: For the first time, the results from this
work corroborate the literature, showing that A. edulis can be used as a natural
anti-inflammatory agent. Moreover, both EOAE and viridiflorol exhibited
biological activities, such as anti-mycobacterial, anti-inflammatory and
antioxidant activity.
PMID- 27612436
TI - Anti-dsDNA antibodies and resident renal cells - Their putative roles in
pathogenesis of renal lesions in lupus nephritis.
AB - Lupus nephritis affects up to 70% of patients with systemic lupus erythematosus
and is an important treatable cause of kidney failure. Cardinal features of lupus
nephritis include loss of self-tolerance, production of autoantibodies, immune
complex deposition and immune-mediated injury to the kidney, resulting in
increased cell proliferation, apoptosis, and induction of inflammatory and
fibrotic processes that destroy normal nephrons. The production anti-dsDNA
antibodies is a cardinal feature in lupus and their level correlates with disease
activity. In addition to the formation of immune complexes thereby triggering
complement activation, how anti-dsDNA antibodies home to the kidney and induce
pathological processes in the renal parenchyma remain to be fully elucidated.
Data from our laboratory and other investigators show that the properties of anti
dsDNA antibodies vary between patients and change over time, and that anti-dsDNA
antibodies could bind directly to integral cell surface molecules such as annexin
II or alpha-actinin, or indirectly through chromatin material deposited on the
cell surface. The binding of anti-dsDNA antibodies to mesangial cells and
proximal renal tubular epithelial cells triggers downstream inflammatory and
fibrotic pathways, which include the activation of the PKC and MAPK signaling
pathways, increased secretion of pro-inflammatory cytokines and matrix protein
deposition that contribute to pathological processes in the renal parenchyma.
PMID- 27612435
TI - White matter integrity between left basal ganglia and left prefrontal cortex is
compromised in gambling disorder.
AB - Pathological gambling (PG) is a behavioral addiction characterized by an
inability to stop gambling despite the negative consequences, which may be
mediated by cognitive flexibility deficits. Indeed, impaired cognitive
flexibility has previously been linked to PG and also to reduced integrity of
white matter connections between the basal ganglia and the prefrontal cortex. It
remains unclear, however, how white matter integrity problems relate to cognitive
inflexibility seen in PG. We used a cognitive switch paradigm during functional
magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy
controls (HCs; n = 26). Cognitive flexibility performance was measured
behaviorally by accuracy and reaction time on the switch task, while brain
activity was measured in terms of blood oxygen level-dependent responses. We also
used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in
combination with tract-based spatial statistics and probabilistic fiber tracking
to assess white matter integrity between the basal ganglia and the dorsolateral
prefrontal cortex. Although there were no significant group differences in either
task performance, related neural activity or tract-based spatial statistics, PGs
did show decreased white matter integrity between the left basal ganglia and
prefrontal cortex. Our results complement and expand similar findings from a
previous study in alcohol-dependent patients. Although we found no association
between white matter integrity and task performance here, decreased white matter
connections may contribute to a diminished ability to recruit prefrontal networks
needed for regulating behavior in PG. Hence, our findings could resonate an
underlying risk factor for PG, and we speculate that these findings may extend to
addiction in general.
PMID- 27612437
TI - Dynamic Phosphorylation of the Myocyte Enhancer Factor 2Calpha1 Splice Variant
Promotes Skeletal Muscle Regeneration and Hypertrophy.
AB - The transcription factor MEF2C (Myocyte Enhancer Factor 2C) plays an established
role in the early steps of myogenic differentiation. However, the involvement of
MEF2C in adult myogenesis and in muscle regeneration has not yet been
systematically investigated. Alternative splicing of mammalian MEF2C transcripts
gives rise to two mutually exclusive protein variants: MEF2Calpha2 which exerts a
positive control of myogenic differentiation, and MEF2Calpha1, in which the
alpha1 domain acts as trans-repressor of the MEF2C pro-differentiation activity
itself. However, MEF2Calpha1 variants are persistently expressed in
differentiating cultured myocytes, suggesting a role in adult myogenesis. We
found that overexpression of both MEF2Calpha1/alpha2 proteins in a mouse model of
muscle injury promotes muscle regeneration and hypertrophy, with each isoform
promoting different stages of myogenesis. Besides the ability of MEF2Calpha2 to
increase differentiation, we found that overexpressed MEF2Calpha1 enhances both
proliferation and differentiation of primary myoblasts, and activates the
AKT/mTOR/S6K anabolic signaling pathway in newly formed myofibers. The multiple
activities of MEF2Calpha1 are modulated by phosphorylation of Ser98 and Ser110,
two amino acid residues located in the alpha1 domain of MEF2Calpha1. These
specific phosphorylations allow the interaction of MEF2Calpha1 with the peptidyl
prolyl isomerase PIN1, a regulator of MEF2C functions. Overall, in this study we
established a novel regulatory mechanism in which the expression and the
phosphorylation of MEF2Calpha1 are critically required to sustain the adult
myogenesis. The described molecular mechanism will represent a new potential
target for the development of therapeutical strategies to treat muscle-wasting
diseases. Stem Cells 2017;35:725-738.
PMID- 27612438
TI - COMP-Ang1 prevents periodontitic damages and enhances mandible bone growth in an
experimental animal model.
AB - COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of
cartilage oligomeric matrix protein (COMP), is under consideration as a
therapeutic agent enhancing tissue regeneration with increased angiogenesis.
However, the effect of COMP-Ang1 on periodontitic tissue damages and the related
mechanisms are not yet investigated. We initially explored whether a local
delivery of COMP-Ang1 protects lipopolysaccharide (LPS)/ligature-induced
periodontal destruction in rats. As the results, MUCT and histological analyses
revealed that COMP-Ang1 inhibits LPS-mediated degradation of periodontium. COMP
Ang1 also suppressed osteoclast number and the expression of osteoclast-specific
and inflammation-related molecules in the inflamed region of periodontitis rats.
Implanting a COMP-Ang1-impregnated scaffold into critical-sized mandible bone
defects enhanced the amount of bone in the defects with increased expression of
bone-specific markers. The addition of COMP-Ang1 prevented significantly
osteoclast differentiation and activation in LPS-stimulated RAW264.7 macrophages
and inhibited the phosphorylation of c-Jun, mitogen-activated protein kinases,
and cAMP response element-binding protein in the cells. On contrary, COMP-Ang1
increased the level of phosphatidylinositol 3-kinase (PI3K) in LPS-exposed
macrophages and a pharmacological PI3K inhibitor diminished the anti
osteoclastogenic effect of COMP-Ang1. Similarly, COMP-Ang1 blocked the expression
of inflammation-related molecules in LPS-stimulated human periodontal ligament
fibroblasts (hPLFs). Further, the COMP-Ang1 enhanced differentiation of hPLFs
into osteoblasts by stimulating the expression of bone-specific markers, Tie2,
and activator protein-1 subfamily. Collectively, our findings may support the
therapeutic potentials of COMP-Ang1 in preventing inflammatory periodontal
damages and in stimulating new bone growth.
PMID- 27612439
TI - Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8
phosphorylation and thereby induces Runx2 expression in osteoblasts.
AB - Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that also plays crucial
roles in bone regeneration. Recently, we reported that the S1P receptors S1PR1
and S1PR2 were mainly expressed in osteoblast-like cells, and that the S1P/S1PR1
signaling pathway up-regulated osteoprotegerin and osteoblast differentiation.
However, the involvement of S1P/S1PR2 signaling in osteoblast differentiation is
not well understood. Here we investigate the role of S1P/S1PR2-mediated signaling
in osteoblast differentiation and clarify the underlying signaling mechanisms. We
found that an S1P/S1PR2/Gi-independent signaling pathway activated RhoA activity,
leading to phosphorylation of Smad1/5/8 in mouse osteoblast-like MC3T3-E1 cells
and primary osteoblasts. Furthermore, this signaling pathway promoted nuclear
translocation of Smad4, and increased the amount of Smad6/7 protein in the
nucleus. S1P also up-regulated runt-related transcription factor 2 (Runx2)
expression through S1PR2/RhoA/ROCK/Smad1/5/8 signaling. Moreover, we found that
S1P partially triggered S1PR2/RhoA/ROCK pathway leading to bone formation in
vivo. These findings suggest that S1P induces RhoA activity, leading to the
phosphorylation of Smad1/5/8, thereby promoting Runx2 expression and
differentiation in osteoblasts. Our findings describe novel molecular mechanisms
in S1P/S1PR2-mediated osteoblast differentiation that could aid future studies of
bone regeneration.
PMID- 27612440
TI - Advanced quantitative imaging and biomechanical analyses of periosteal fibers in
accelerated bone growth.
AB - PURPOSE: The accepted mechanism explaining the accelerated growth following
periosteal resection is that the periosteum serves as a mechanical restraint to
restrict physeal growth. To test the veracity of this mechanism we first utilized
Second Harmonic Generation (SHG) imaging to measure differences of periosteal
fiber alignment at various strains. Additionally, we measured changes in
periosteal growth factor transcription. Next we utilized SHG imaging to assess
the alignment of the periosteal fibers on the bone both before and after
periosteal resection. Based on the currently accepted mechanism, we hypothesized
that the periosteal fibers adjacent to the physis should be more aligned (under
tension) during growth and become less aligned (more relaxed) following
metaphyseal periosteal resection. In addition, we measured the changes in
periosteal micro- and macro-scale mechanics. METHODS: 30 seven-week old New
Zealand White rabbits were sacrificed. The periosteum was imaged on the bone at
five regions using SHG imaging. One centimeter periosteal resections were then
performed at the proximal tibial metaphyses. The resected periosteal strips were
stretched to different strains in a materials testing system (MTS), fixed, and
imaged using SHG microscopy. Collagen fiber alignment at each strain was then
determined computationally using CurveAlign. In addition, periosteal strips
underwent biomechanical testing in both circumferential and axial directions to
determine modulus, failure stress, and failure strain. Relative mRNA expression
of growth factors: TGFbeta-1, -2, -3, Ihh, PTHrP, Gli, and Patched were measured
following loading of the periosteal strips at physiological strains in a
bioreactor. The periosteum adjacent to the physis of six tibiae was imaged on the
bone, before and after, metaphyseal periosteal resection, and fiber alignment was
computed. One-way ANOVA statistics were performed on all data. RESULTS: Imaging
of the periosteum at different regions of the bone demonstrated complex regional
differences in fiber orientation. Increasing periosteal strain on the resected
strips increased periosteal fiber alignment (p<0.0001). The only exception to
this pattern was the 10% strain on the tibial periosteum, which may indicate
fiber rupture at this non-physiologic strain. Periosteal fiber alignment adjacent
to the resection became less aligned while those adjacent to the physes remained
relatively unchanged before and after periosteal resection. Increasing periosteal
strain on the resected strips increased periosteal fiber alignment (p<0.0001).
The only exception to this pattern was the 10% strain on the tibial periosteum,
which may indicate fiber rupture (and consequent retraction) at this non
physiologic strain. Increasing periosteal strain revealed a significant increase
in relative mRNA expression for Ihh, PTHrP, Gli, and Patched, respectively.
CONCLUSION: Periosteal fibers adjacent to the growth plate do not appear under
tension in the growing limb, and the alignments of these fibers remain unchanged
following periosteal resection. SIGNIFICANCE: The results of this study call into
question the long-accepted role of the periosteum acting as a simple mechanical
tether restricting growth at the physis.
PMID- 27612441
TI - Creatinine Clearance Is Not Equal to Glomerular Filtration Rate and Cockcroft
Gault Equation Is Not Equal to CKD-EPI Collaboration Equation.
AB - Direct oral anticoagulants (DOACs) may require dose reduction or avoidance when
glomerular filtration rate is low. However, glomerular filtration rate is not
usually measured in routine clinical practice. Rather, equations that incorporate
different variables use serum creatinine to estimate either creatinine clearance
in mL/min or glomerular filtration rate in mL/min/1.73 m2. The Cockcroft-Gault
equation estimates creatinine clearance and incorporates weight into the
equation. By contrast, the Modification of Diet in Renal Disease and Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular
filtration rate and incorporate ethnicity but not weight. As a result, an
individual patient may have very different renal function estimates, depending on
the equation used. We now highlight these differences and discuss the impact on
routine clinical care for anticoagulation to prevent embolization in atrial
fibrillation. Pivotal DOAC clinical trials used creatinine clearance as a
criterion for patient enrollment, and dose adjustment and Federal Drug
Administration recommendations are based on creatinine clearance. However,
clinical biochemistry laboratories provide CKD-EPI glomerular filtration rate
estimations, resulting in discrepancies between clinical trial and routine use of
the drugs.
PMID- 27612442
TI - Not All Erythema Migrans Lesions Are Lyme Disease.
AB - BACKGROUND: Lyme disease is the number one arthropod-transmitted disease in the
US, and one of the diagnostic criteria for the illness is development of an
erythematous bull's-eye rash around a tick bite that may expand over time, hence
the term erythema migrans. However, there are other erythema migrans-like rashes,
such as those from a condition known as southern tick-associated rash illness.
This article describes a patient with an erythema migrans-like lesion similar to
that associated with Lyme disease, resulting from a bite by a nymphal-stage lone
star tick, Amblyomma americanum. METHODS: A tick removed from the center of an
erythema migrans-like lesion in a patient was identified to species and then
submitted to the Centers for Disease Control and Prevention for testing for the
agent of Lyme disease, Borrelia burgdorferi. The patient was evaluated by an
internist 7 weeks later. After another 3 weeks, the patient's blood was tested
serologically for Lyme disease by American Esoteric Laboratories, Memphis, Tenn.
RESULTS: Both the tick and human blood sample from this patient were negative for
evidence of Lyme disease. Clinically, other than the erythema migrans-like
lesion, the patient displayed no signs or symptoms consistent with Lyme disease.
CONCLUSIONS: This case presents clinical, serological, and molecular evidence
that erythema migrans lesions may occur after tick bites in patients and that
these lesions may not be due to infection with the agent of Lyme disease.
PMID- 27612443
TI - Diagnosis and laparoscopic management of a rudimentary horn pregnancy: Role of
three-dimensional ultrasound.
AB - Rudimentary horn pregnancy occurs in 1 in 76,000-150,000 pregnancies and causes
uterine rupture in about 80% of cases. The use of three-dimensional transvaginal
ultrasound seems to be useful for its early detection. We present a case of an 8
week pregnancy in a rudimentary horn, managed by laparoscopic excision. (c) 2016
Wiley Periodicals, Inc. J Clin Ultrasound 45:112-115, 2017.
PMID- 27612444
TI - Factors associated with regular physical exercise and consumption of fruits and
vegetables among Mexican older adults.
AB - BACKGROUND: To analyze the factors associated with regular physical exercise and
routine consumption of fruits and vegetables, and both healthy behaviors among
Mexican older adults. METHODS: We conducted a secondary data analysis of the
baseline data (2014) of the Study on Obesity, Sarcopenia and Fragility in older
adults affiliated with the Mexican Institute of Social Security. The study
included 948 adults who were >=60 years of age. Multiple Poisson regression was
performed. RESULTS: Routine consumption of fruits and vegetables was reported by
53.8 % of older adults, 42.7 % reported engaging in regular physical exercise and
23.1 % reported participating in both types of healthy behaviors. Women, adults
with a stable income, those with a self-perception of good health and those with
a history of physical exercise at the age of 50 years had an increased likelihood
of engaging in healthy eating and regular physical activity. CONCLUSIONS: Many
older adults do not routinely consume fruits and vegetables or engage in regular
physical exercise despite the fact that most have a fixed income and a social
network. It is relevant to conduct research-based interventions that take into
account the contextual factors to promote healthy behaviors.
PMID- 27612445
TI - "Complex" dystonia is not a category in the new 2013 consensus classification.
PMID- 27612446
TI - Design and protocol for the Dialysis Optimal Health Program (DOHP) randomised
controlled trial.
AB - BACKGROUND: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are
serious and growing health problems with enormous impact on psychological and
social functioning. Despite high rates of comorbid depression and anxiety in
these patient populations, and the adverse impact these have upon treatment
adherence, quality of life, social connectedness and healthcare costs there has
been little attention focused on the prevention or management of these problems.
Thus, our aim was to evaluate the Dialysis Optimal Health Program (DOHP) that
adopts a person-centred approach and engages collaborative therapy to educate and
support those diagnosed with ESKD who are commencing dialysis. METHODS: The study
design is a randomised controlled trial. Ninety-six adult patients initiating
haemodialysis or peritoneal dialysis will be randomly allocated to either the
intervention (DOHP) or usual care group. Participants receiving the intervention
will receive nine (8 + 1 booster session) sequential sessions based on a
structured information/workbook, psychosocial and educational supports and skills
building. The primary outcome measures are depression and anxiety (assessed by
the Hospital Anxiety and Depression Scale; HADS). Secondary outcomes include
health-related quality of life (assessed by the Kidney Disease Quality of Life
instrument; KDQOL), self-efficacy (assessed by General Self-Efficacy Scale) and
clinical indices (e.g. albumin and haemoglobin levels). Cost-effectiveness
analysis and process evaluation will also be performed to assess the economic
value and efficacy of the DOHP. Primary and secondary measures will be collected
at baseline and at 3-, 6-, and 12-month follow-up time points. DISCUSSION: We
believe that this innovative trial will enhance knowledge of interventions aimed
at supporting patients in the process of starting dialysis, and will broaden the
focus from physical symptoms to include psychosocial factors such as depression,
anxiety, self-efficacy, wellbeing and community support. The outcomes associated
with this study are significant in terms of enhancing an at-risk population's
psychosocial health and reducing treatment-related costs and associated pressures
on the healthcare system. TRIAL REGISTRATION: ANZCTR no. 12615000810516 .
Registered on 5 August 2015.
PMID- 27612447
TI - An appraisal of meta-analysis guidelines: how do they relate to safety outcomes?
AB - Although well developed to assess efficacy questions, meta-analyses and, more
generally, systematic reviews, have received less attention in application to
safety-related questions. As a result, many open questions remain on how best to
apply meta-analyses in the safety setting. This appraisal attempts to: (i)
summarize the current guidelines for assessing individual studies, systematic
reviews, and network meta-analyses; (ii) describe several publications on safety
meta-analytic approaches; and (iii) present some of the questions and issues that
arise with safety data. A number of gaps in the current quality guidelines are
identified along with issues to consider when performing a safety meta-analysis.
While some work is ongoing to provide guidance to improve the quality of safety
meta-analyses, this review emphasizes the critical need for better reporting and
increased transparency regarding safety data in the systematic review guidelines.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27612448
TI - Primary rare anaplastic large cell lymphoma, ALK positive in small intestine:
case report and review of the literature.
AB - BACKGROUND: Primary anaplastic large cell lymphoma, ALK positive in small
intestine is clinically rare and the clinical, radiological and pathological
information are generally not availab le . Here, we report a case of 32-year-old
male with ALK positive anaplastic large cell lymphoma at the junction of jejunum
and ileum, and highlight the clinicopathological features and the differential
diagnosis of this type lymphoma. CASE PRESENTATION: The patient presented with
right middle abdominal mass for 1 month with sporadic pain. Computed tomography
(CT) showed a mass measured 8.5 * 7.4 * 4 cm at the junction of jejunum and
ileum. The diagnosis was made after pathological examination of the excised
tissue by enterectomy. Grossly, the mass was located predominately in intestinal
wall with grayish appearance and blurry boundary. Microscopically, almost all
layers of the intestinal wall were infiltrated by pleomorphic tumor cells with
diffuse and cohesive growth pattern. The neoplastic cells were mainly medium to
large size with moderate basophilic cytoplasm. Most of them had hyperchromatic
nuclei and prominent nucleoli. "Hallmark" cells were easily detected.
Immunohistochemically, tumor cells are characterized by CD30, ALK, CD5, TIA-1,
Granzyme B, EMA positive staining, and CD2, CD3, CD7, CD4, CD8, CD20, CD79a
negative staining. The Epstein-Barr virus encoded RNAs (EBERs) genome was also
negative. A diagnosis as primary small intestinal ALK positive anaplastic large
cell lymphoma was finally made. The patient received CHOP chemotherapy and is
alive till now without recurrence 5 months after enterectomy. CONCLUSIONS:
Primary small intestinal ALK positive anaplastic large cell lymphoma is rare. The
accurate diagnosis should be based on combined consideration of clinical
characteristics, CT image and pathological features, and should be distinguished
from other lymphomas or solid tumors in small intestine.
PMID- 27612449
TI - A hybrid computational strategy to address WGS variant analysis in >5000 samples.
AB - BACKGROUND: The decreasing costs of sequencing are driving the need for cost
effective and real time variant calling of whole genome sequencing data. The
scale of these projects are far beyond the capacity of typical computing
resources available with most research labs. Other infrastructures like the cloud
AWS environment and supercomputers also have limitations due to which large scale
joint variant calling becomes infeasible, and infrastructure specific variant
calling strategies either fail to scale up to large datasets or abandon joint
calling strategies. RESULTS: We present a high throughput framework including
multiple variant callers for single nucleotide variant (SNV) calling, which
leverages hybrid computing infrastructure consisting of cloud AWS, supercomputers
and local high performance computing infrastructures. We present a novel binning
approach for large scale joint variant calling and imputation which can scale up
to over 10,000 samples while producing SNV callsets with high sensitivity and
specificity. As a proof of principle, we present results of analysis on Cohorts
for Heart And Aging Research in Genomic Epidemiology (CHARGE) WGS freeze 3
dataset in which joint calling, imputation and phasing of over 5300 whole genome
samples was produced in under 6 weeks using four state-of-the-art callers. The
callers used were SNPTools, GATK-HaplotypeCaller, GATK-UnifiedGenotyper and
GotCloud. We used Amazon AWS, a 4000-core in-house cluster at Baylor College of
Medicine, IBM power PC Blue BioU at Rice and Rhea at Oak Ridge National
Laboratory (ORNL) for the computation. AWS was used for joint calling of 180 TB
of BAM files, and ORNL and Rice supercomputers were used for the imputation and
phasing step. All other steps were carried out on the local compute cluster. The
entire operation used 5.2 million core hours and only transferred a total of 6 TB
of data across the platforms. CONCLUSIONS: Even with increasing sizes of whole
genome datasets, ensemble joint calling of SNVs for low coverage data can be
accomplished in a scalable, cost effective and fast manner by using heterogeneous
computing platforms without compromising on the quality of variants.
PMID- 27612451
TI - Rufibacter quisquiliarum sp. nov., a new member of the phylum Bacteroidetes
isolated from a bioreactor treating landfill leachate.
AB - A novel bacterium, CAI-18bT, was isolated from a bioreactor that treated landfill
leachate using an oligotrophic growth medium. Phylogenetic analysis based on the
16S rRNA gene sequence revealed that strain CAI-18bT is a member of the genus
Rufibacter, showing 97.1 % pairwise similarity to Rufibacter roseus H359T, 96.4 %
to Rufibacter tibetensis 1351T, 96.4 % to Rufibacter glacialis MDT1-10-3T and
96.0 % to Rufibacter immobilis MCC P1T. Strain CAI-18bT was rod-shaped, motile,
oxidase- and catalase-positive. The predominant fatty acids were iso-C15 : 0
(24.1 %) and iso-C17 : 1 I (22.3 %), the major respiratory quinone was MK-7, and
the predominant polar lipids were phosphatidylethanolamine and an unknown
aminophospholipid. The G+C content of the genomic DNA of strain CAI-18bT was 50.7
mol%. The novel bacterium can be distinguished from related type strains based on
its ability to assimilate N-acetylglucosamine and gentiobiose. On the basis of
the phenotypic, chemotaxonomic and molecular data, strain CAI-18bT represents a
novel species of the genus Rufibacter, for which the name Rufibacter
quisquiliarum sp. nov. is proposed. The type strain is CAI-18bT (=DSM
29854T=NCAIM B.02614T).
PMID- 27612450
TI - Increased chemotaxis and activity of circulatory myeloid progenitor cells may
contribute to enhanced osteoclastogenesis and bone loss in the C57BL/6 mouse
model of collagen-induced arthritis.
AB - Our study aimed to determine the functional activity of different osteoclast
progenitor (OCP) subpopulations and signals important for their migration to bone
lesions, causing local and systemic bone resorption during the course of collagen
induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II
collagen (CII), and assessed by clinical scoring and detection of anti-CII
antibodies. We observed decreased trabecular bone volume of axial and
appendicular skeleton by histomorphometry and micro-computed tomography as well
as decreased bone formation and increased bone resorption rate in arthritic mice
in vivo. In the affected joints, bone loss was accompanied with severe osteitis
and bone marrow hypercellularity, coinciding with the areas of active osteoclasts
and bone erosions. Flow cytometry analysis showed increased frequency of putative
OCP cells (CD3- B220- NK1.1- CD11b-/lo CD117+ CD115+ for bone marrow and CD3-
B220- NK1.1- CD11b+ CD115+ Gr-1+ for peripheral haematopoietic tissues), which
exhibited enhanced differentiation potential in vitro. Moreover, the total CD11b+
population was expanded in arthritic mice as well as CD11b+ F4/80+ macrophage,
CD11b+ NK1.1+ natural killer cell and CD11b+ CD11c+ myeloid dendritic cell
populations in both bone marrow and peripheral blood. In addition, arthritic mice
had increased expression of tumour necrosis factor-alpha, interleukin-6, CC
chemokine ligand-2 (Ccl2) and Ccl5, with increased migration and differentiation
of circulatory OCPs in response to CCL2 and, particularly, CCL5 signals. Our
study characterized the frequency and functional properties of OCPs under
inflammatory conditions associated with arthritis, which may help to clarify
crucial molecular signals provided by immune cells to mediate systemically
enhanced osteoresorption.
PMID- 27612452
TI - Mergeomics: a web server for identifying pathological pathways, networks, and key
regulators via multidimensional data integration.
AB - BACKGROUND: Human diseases are commonly the result of multidimensional changes at
molecular, cellular, and systemic levels. Recent advances in genomic technologies
have enabled an outpour of omics datasets that capture these changes. However,
separate analyses of these various data only provide fragmented understanding and
do not capture the holistic view of disease mechanisms. To meet the urgent needs
for tools that effectively integrate multiple types of omics data to derive
biological insights, we have developed Mergeomics, a computational pipeline that
integrates multidimensional disease association data with functional genomics and
molecular networks to retrieve biological pathways, gene networks, and central
regulators critical for disease development. RESULTS: To make the Mergeomics
pipeline available to a wider research community, we have implemented an online,
user-friendly web server ( http://mergeomics. RESEARCH: idre.ucla.edu/ ). The web
server features a modular implementation of the Mergeomics pipeline with detailed
tutorials. Additionally, it provides curated genomic resources including tissue
specific expression quantitative trait loci, ENCODE functional annotations,
biological pathways, and molecular networks, and offers interactive visualization
of analytical results. Multiple computational tools including Marker Dependency
Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted
Key Driver Analysis (wKDA) can be used separately or in flexible combinations.
User-defined summary-level genomic association datasets (e.g., genetic,
transcriptomic, epigenomic) related to a particular disease or phenotype can be
uploaded and computed real-time to yield biologically interpretable results,
which can be viewed online and downloaded for later use. CONCLUSIONS: Our
Mergeomics web server offers researchers flexible and user-friendly tools to
facilitate integration of multidimensional data into holistic views of disease
mechanisms in the form of tissue-specific key regulators, biological pathways,
and gene networks.
PMID- 27612453
TI - Stigmatized by association: challenges for abortion service providers in Ghana.
AB - BACKGROUND: Unsafe abortion is an issue of public health concern and contributes
significantly to maternal morbidity and mortality globally. Abortion evokes
religious, moral, ethical, socio-cultural and medical concerns which mean it is
highly stigmatized and this poses a threat to both providers and researchers.
This study sought to explore challenges to providing safe abortion services from
the perspective of health providers in Ghana. METHODS: A descriptive qualitative
study using in-depth interviews was conducted. The study was conducted in three
(3) hospitals and five (5) health centres in the capital city in Ghana.
Participants (n = 36) consisted of obstetrician/gynaecologists, nurse-midwives
and pharmacists. RESULTS: Stigma affects provision of safe-abortion services in
Ghana in a number of ways. The ambiguities in Ghanaian abortion law and lack of
overt institutional support for practitioners increased reluctance to openly
provide for fear of stigmatisation and legal threat. Negative provider attitudes
that stigmatised women seeking abortion care were frequently driven by socio
cultural and religious norms that highly stigmatise abortion practice. Exposure
to higher levels of education, including training overseas, seemed to result in
more positive, less stigmatising views towards the need for safe abortion
services. Nevertheless, physicians open to practicing abortion were still very
concerned about stigma by association. CONCLUSIONS: Stigma constitutes an
overarching impediment for abortion service provision. It affects health
providers providing such services and even researchers who study the subject.
Exposure to wider debate and education seem to influence attitudes and values
clarification training may prove useful. Proper dissemination of existing
guidelines and overt institutional support for provision of safe services also
needs to be rolled out.
PMID- 27612455
TI - A novel artificial tissue simulator for endoscopic submucosal resection training
a pilot study.
AB - BACKGROUND: We developed a novel artificial simulator for endoscopic submucosal
dissection (ESD) as a bridge between instructional videos and animal tissue
training and aimed to evaluate the feasibility of using an artificial tissue
model in ESD training. METHODS: Eight gastroenterology fellows from one medical
center were enrolled in this ESD training program. Before and after the simulator
training, attendees indicated on a 5-point scale the degree of difficulty in
performing the following procedures: lesion marking, mucosal pre-cutting,
circumferential incision, submucosal dissection, and hemostasis. After the
simulator training, the participants completed a questionnaire regarding their
opinions on the degree of realism and the feasibility of using this model for
training. RESULTS: After watching an instructional video, attendees felt that the
most difficult techniques were submucosal dissection and hemostasis. After using
the artificial tissue simulator model, the attendees felt more confident in
performing performing lesion marking (p = 0.026) and submucosal dissection (p =
0.037). However, they still felt that hemostasis was the most difficult
techniques to master. Overall, the attendees thought the simulator was realistic
in simulated lesion marking and its use was feasible for simulated lesion marking
and submucosal dissection. CONCLUSION: Our pilot study shows the feasibility of
using a novel artificial tissue in performing ESD and we believe that the
artificial tissue simulator acts well as a bridge between instructional videos
and animal model training. The model is reusable and inexpensive, and could
disseminate the techniques of the ESD more easily and quickly.
PMID- 27612454
TI - Circumventing 'free care' and 'shouting louder': using a health systems approach
to study eye health system sustainability in government and mission facilities of
north-west Tanzania.
AB - BACKGROUND: Little is known about the contributions of faith-based organisations
(FBOs) to health systems in Africa. In the specialist area of eye health,
international and domestic Christian FBOs have been important contributors as
service providers and donors, but they are also commonly critiqued as having
developed eye health systems parallel to government structures which are
unsustainable. METHODS: In this study, we use a health systems approach
(quarterly interviews, a participatory sustainability analysis exercise and a
social network analysis) to describe the strategies used by eye care
practitioners in four hospitals of north-west Tanzania to navigate the
government, church mission and donor rules that govern eye services delivery
there. RESULTS: Practitioners in this region felt eye care was systemically
neglected by government and therefore was 'all under the NGOs', but support from
international donors was also precarious. Practitioners therefore adopted four
main strategies to improve the sustainability of their services: (1) maintain
'sustainability funds' to retain financial autonomy over income; (2) avoid
granting government user fee exemptions to elderly patients who are the majority
of service users; (3) expand or contract outreach services as financial
circumstances change; and (4) access peer support for problem-solving and
advocacy. Mission-based eye teams had greater freedom to increase their income
from user fees by not implementing government policies for 'free care'. Teams in
all hospitals, however, found similar strategies to manage their programmes even
when their management structures were unique, suggesting the importance of
informal rules shared through a peer network in governing eye care in this
pluralistic health system. CONCLUSIONS: Health systems research can generate new
evidence on the social dynamics that cross public and private sectors within a
local health system. In this area of Tanzania, Christian FBOs' investments are
important, not only in terms of the population health outcomes achieved by teams
they support, but also in the diversity of organisational models they contribute
to in the wider eye health system, which facilitates innovation.
PMID- 27612456
TI - Effects of Zinc Supplementation on DNA Damage in Rats with Experimental Kidney
Deficiency.
AB - This study was carried out to determine the effect of zinc on oxidative DNA
damage in rats with experimental acute and chronic kidney deficiency. Six groups
of five Wistar-Albino rats each were assigned as controls (C), acute kidney
deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc
supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented
chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2'-deoxyguanosine (8
OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in
the C group than those of rats with CKD but lower than that of all the other
groups (p < 0.05). There were no significant differences between the controls and
the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the
highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was
greater in acute renal failure than in rats with chronic renal failure. The DNA
damage in the zinc group was significantly higher than in the controls.
PMID- 27612457
TI - Characterization, treatment patterns, and patient-related outcomes of patients
with Fragile X syndrome in Germany: final results of the observational EXPLAIN
FXS study.
AB - BACKGROUND: As data on the phenotype, characteristics and management of patients
with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in
Germany in experienced centres involved in the treatment of such patients.
METHODS: EXPLAIN-FXS is a prospective observational (non-interventional) study
(registry) performed between April 2013 and January 2016 at 18 sites in Germany.
Requirements for patient participation included confirmed diagnosis of FXS by
genetic testing (>200 CGG repeats) and written informed consent. Patients were
followed for up to 2 years. RESULTS: Seventy-five patients (84.0 % males, mean
age 16.7 +/- 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6
item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was
6.9 +/- 2.5 points. At least one neurological finding each was noted in 53
patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of
fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients
(5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was
not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety
disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in
36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and
other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour
Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71
patients at first documentation, was 48.4 +/- 27.8 (median 45.0, range 5-115).
The mean visual analogue scale (VAS) score, obtained in 59 patients at first
documentation, was 84.9 +/- 14.6 points (median 90; range 50 - 100). CONCLUSIONS:
This report describes the largest cohort of patients with FXS in Europe. The
reported observations indicate a substantial burden of disease for patients and
their caregivers. Based on these observations, an early expert psychiatric
diagnosis is recommended for suspected FXS patients. Further recommendations
include multimodal and multi-professional management that is tailored to the
individual patient's needs. TRIAL REGISTRATION: The ClinTrials.gov identifier is
NCT01711606 . Registered on 18 October 2012.
PMID- 27612458
TI - An inter-laboratory comparison of standard membrane-feeding assays for evaluation
of malaria transmission-blocking vaccines.
AB - BACKGROUND: An effective malaria transmission-blocking vaccine may play an
important role in malaria elimination efforts, and a robust biological assay is
essential for its development. The standard membrane-feeding assay (SMFA) for
Plasmodium falciparum infection of mosquitoes is considered a "gold standard"
assay to measure transmission-blocking activity of test antibodies, and has been
utilized widely in both non-clinical and clinical studies. While several studies
have discussed the inherent variability of SMFA within a study group, there has
been no assessment of inter-laboratory variation. Therefore, there is currently
no assurance that SMFA results are comparable between different studies. METHODS:
Mouse anti-Pfs25 monoclonal antibody (mAb, 4B7 mAb), rat anti-Pfs48/45 mAb
(85RF45.1 mAb) and a human polyclonal antibody (pAb) collected from a malaria
exposed adult were tested at the same concentrations (6-94 MUg/mL for 4B7, 1.2
31.3 MUg/mL for 85RF45.1 and 23-630 MUg/mL for human pAb) in two laboratories
following their own standardized SMFA protocols. The mAbs and pAb, previously
shown to have strong inhibition activities in the SMFA, were tested at three or
four concentrations in two or three independent assays in each laboratory, and
percent inhibition in mean oocyst intensity relative to a control in the same
feed was determined in each feeding experiment. RESULTS: Both monoclonal and
polyclonal antibodies dose-dependently reduced oocyst intensity in all
experiments performed at the two test sites. In both laboratories, the inter
assay variability in percent inhibition in oocyst intensity decreased at higher
levels of inhibition, regardless of which antibody was tested. At antibody
concentrations that led to a >80 % reduction in oocyst numbers, the inter
laboratory variations were in the same range compared with the inter-assay
variation observed within a single laboratory, and the differences in best
estimates from multiple feeds between the two laboratories were <5 percentage
points. CONCLUSIONS: This study confirms previous reports that the precision of
the SMFA increases with increasing percent inhibition. Moreover, the variation
between the two laboratories is not greater than the variation observed within a
laboratory. The findings of this study provide guidance for comparison of SMFA
data from different laboratories.
PMID- 27612459
TI - Adipose-derived mesenchymal stem cells from patients with atherosclerotic
renovascular disease have increased DNA damage and reduced angiogenesis that can
be modified by hypoxia.
AB - BACKGROUND: Adipose-derived MSC (AMSCs) possess angiogenic and immunomodulatory
properties that may modulate kidney regeneration. Whether these properties are
retained in older patients with atherosclerotic vascular disease is poorly
understood. Hypoxic conditions are known to modify properties and growth
characteristics of AMSCs. We tested the hypothesis that AMSCs from older patients
with atherosclerotic renovascular disease (RVD) differ from normal kidney donors,
and whether hypoxia changes their functional and molecular properties to promote
angiogenesis. METHODS: AMSCs from 11 patients with RVD (mean age =74.5 years) and
10 healthy kidney donors (mean age = 51.2 years) were cultured under normoxia (20
% O2) and hypoxia (1 % O2) for 3-4 days until they reached 80 % confluency. We
analyzed expression of genes and microRNAs using RNA sequencing and real-time
quantitative rt-PCR. Protein expression of selected angiogenic factors (VEGF,
IGF, HGF and EGF) were quantified in conditioned media using ELISAs. Apoptosis
was tested using Annexin IV staining. RESULTS: Normoxic AMSC from RVD patients
grew normally, but exhibited increased DNA damage and reduced migration. VEGF
protein secretion was significantly lower in the RVD AMSCs (0.08 vs 2.4 ng/mL/
cell, p <0.05) while HGF was higher. Both trends were reversed during growth
under hypoxic conditions. Hypoxia upregulated pro-angiogenic mRNAs expression in
AMSCs (VEGF, FGF, STC and ANGPTL4), and downregulated expression of many miRNAs
(e.g., miR-15a, miR-16, miR-93, miR-424, 126, 132, 221) except miR-210.
CONCLUSIONS: Thus, although AMSC from patients with RVD had increased DNA damage
and reduced migration, hypoxia stimulated pro-angiogenic responses via increased
expression of angiogenic genes, VEGF secretion and induction of the hypoxia
inducible miR-210, while downregulating angiogenesis-related miRNAs.
PMID- 27612460
TI - Vaccine Case-Population: A New Method for Vaccine Safety Surveillance.
AB - INTRODUCTION: The case-population approach compares exposure among cases to that
of their source population. By using aggregated data to estimate the denominator,
this approach can provide a real-time estimate of an association that could be
particularly valuable to explore urgent vaccine safety concerns and to generate
signals during a vaccine campaign. OBJECTIVE: Our objective was to present the
vaccine case-population method, a method derived from the case-population
approach and adapted for vaccine safety surveillance, and to test it using
several published examples. METHODS: For the vaccine case-population method,
exposure in the population is estimated from the sum of at-risk periods using the
number of vaccinated individuals, or data of vaccine sales, and the at-risk
period considered for the vaccine-event pair. The vaccine case-population method
was applied to data from published case-control studies retrieved from the
MEDLINE database and having quantified risks associated with vaccines. Odds
ratios derived from the vaccine case-population method were compared with those
from published case-control studies. RESULTS: A total of 20 vaccine-event pairs
were retrieved in which the vaccine case-population method could be applied. For
all identified vaccine-event pairs, when a significant association was found
using the vaccine case-population method, a significant association was also
found in the corresponding case-control study. Conversely, when no association
was found by the vaccine case-population method, no association was found in the
corresponding case-control study. CONCLUSION: These results suggest that the
vaccine case-population method can produce coherent conclusions and may be used
in the future for prospective investigation of urgent vaccine safety concerns or
for the prospective generation of vaccine safety signals. This method could also
be used to identify selection bias from cases excluded from the case-control
study.
PMID- 27612461
TI - The effects of early high-volume hemofiltration on prolonged cardiac arrest in
rats with reperfusion by cardiopulmonary bypass: a randomized controlled animal
study.
AB - BACKGROUND: It is not yet clear whether hemofiltration can reduce blood cytokine
levels sufficiently to benefit patients who suffer prolonged cardiac arrest (CA)
treated with cardiopulmonary bypass (CPB). We sought to assess effects of high
volume and standard volume continuous veno-venous hemofiltration (CVVH) on blood
cytokine levels and survival in a rat model of prolonged CA treated with CPB.
METHODS: Sprague-Dawley male rats were subjected to 12 min of asphyxia to induce
CA. CPB was initiated for resuscitation of animals and maintained for 30 min.
Twenty-four rats were randomly assigned into three groups: without CVVH treatment
(sham); standard volume CVVH at a filtration rate of 35-45 mL/kg/h; and high
volume hemofiltration (HVHF, 105-135 mL/kg/h). Hemofiltration was started
simultaneously with CPB and maintained for 6 h. Plasma TNFalpha and IL-6 levels
were measured at baseline, 0.5, 1, 2, 3, and 6 h after reperfusion. Survival
time, neurological deficit score, and hemodynamic status were assessed. RESULTS:
All animals survived over 6 h and died within 24 h. There were no significant
differences in survival time (log-rank test, sham vs. CVVH; p = 0.49, sham vs.
HVHF; p = 0.33) or neurological deficit scores (ANOVA, p = 0.14) between the
groups. There were no significant differences in blood cytokine levels between
the groups. Mean blood pressure in sham group animals increased to 1.5-fold
higher than baseline levels at 30 min. HVHF significantly reduced blood pressure
to 0.7-fold of sham group (p < 0.01). CONCLUSIONS: There was no improvement in
mortality, neurological dysfunction, TNFalpha, or IL-6 levels in rats after
prolonged CA with CPB on either hemofiltration group when compared to the sham
group.
PMID- 27612462
TI - A cell-level model of pharmacodynamics-mediated drug disposition.
AB - We aimed to develop a cell-level pharmacodynamics-mediated drug disposition
(PDMDD) model to analyze in vivo systems where the PD response to a drug has an
appreciable effect on the pharmacokinetics (PK). An existing cellular level model
of PD stimulation was combined with the standard target-mediated drug disposition
(TMDD) model and the resulting model structure was parametrically identifiable
from typical in vivo PK and PD data. The PD model of the cell population was
controlled by the production rate k in and elimination rate k out which could be
stimulated or inhibited by the number of bound receptors on a single cell.
Simulations were performed to assess the impact of single and repeated dosing on
the total drug clearance. The clinical utility of the cell-level PDMDD model was
demonstrated by fitting published data on the stimulatory effects of filgrastim
on absolute neutrophil counts in healthy subjects. We postulated repeated dosing
as a means of detecting and quantifying PDMDD as a single dose might not be
sufficient to elicit the cellular response capable of altering the receptor pool
to visibly affect drug disposition. In the absence of any PD effect, the model
reduces down to the standard TMDD model. The applications of this model can be
readily extended to include chemotherapy-induced cytopenias affecting clearance
of endogenous hematopoietic growth factors, different monoclonal antibodies and
immunogenicity effects on PK.
PMID- 27612463
TI - Consolidative Technique Otoplasty: Comprehensive Approach in Combining
Techniques.
AB - BACKGROUND: This study aimed to present the long-term results of the
consolidative technique otoplasty (CTO). METHODS: Patient age, sex, duration of
follow-up, and how the deformity (bilateral-unilateral) occurred were determined.
The kind of anesthesia, duration of surgery, surgical techniques used during the
operation were reported, and the preoperative and postoperative distances between
the ear and head were measured at four points (SUP: The highest point of the
helix; SCA: the concha superior sticking points; ICA: stick point of Concha at
the inferior; and lobular). Early- and late-term complications were recorded in
the postoperative period. RESULTS: A total of 63 (21M-42FM) patients whose
average age of 21:41 +/- 8.96 (7-41), 119 ears (Right: 58/Left: 61) were operated
on with this technique between 2013 and 2015. Mean follow-up was 18:22 +/- 9:42
months. Anterior scoring was performed for three patients; concha resection was
performed in 17 patients. Fifty-five patients were operated on as primary
otoplasties and eight were secondary otoplasties. When the preoperative and
postoperative SUP, SCA, ICA, and lobule measurements for both ears were compared,
the postoperative values were found to be significantly decreased (p < 0.001).
CONCLUSIONS: This technique may be an alternative in the repairs of prominent
ears, and it provides an intervention opportunity for all the anatomical
structures. LEVEL OF EVIDENCE V: This journal requires that authors assign a
level of evidence to each article. For a full description of these Evidence-Based
Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 27612465
TI - Crossmodal spatial congruence effects: visual dominance in conditions of
increased and reduced selection difficulty.
AB - The present study investigated crossmodal spatial congruence effects in the cued
modality-switching paradigm of Lukas, Philipp, and Koch (Psychol Res 74:255-267,
2010). Bimodal auditory and visual spatial-location stimuli were presented
simultaneously, and participants responded with a left or right key press to the
left or right location of the stimulus in the cued modality. Results replicated
the asymmetric spatial congruence effects reported by Lukas et al. for a
compatible mapping of stimulus locations to responses, with higher performance
cost for spatially incongruent stimuli when the relevant modality was auditory
and the irrelevant modality visual than when the relation was opposite. A similar
result pattern was found when the stimulus-response mapping was incompatible and
when the responses differed along an orthogonal vertical axis, consistent with
the view that the visual dominance effect depends on correspondence between the
auditory and visual stimulus locations. Blocking the relevant modality to remove
uncertainty reduced but did not eliminate the visual dominance effect, even with
brief stimulus durations. The findings provide broad support for crossmodal
visual dominance, even when participants know to direct attention to the auditory
modality.
PMID- 27612464
TI - A prospective study of the antiemetic effect of palonosetron in malignant
lymphoma patients treated with the CHOP regimen.
AB - To identify strategies for reducing emesis induced by the CHOP regimen, which
includes high-dose steroids, we prospectively evaluated the efficacy of
palonosetron in Japanese patients. Palonosetron was administered at a dose of
0.75 mg via intravenous injection over 30 min before chemotherapy on day 1.
Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV)
incidence from the start of chemotherapy until 168 h afterwards, in which they
documented the occurrence and severity of nausea, vomiting, anorexia, and the use
of rescue medication. The primary endpoint was the overall occurrence rate of
nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively,
including all grades. The rates and severity of symptoms tended to worsen 120-168
h after completing oral prednisolone. We defined complete response (CR) as no
vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg
treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h)
were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for
day 6 and, thereafter, should be investigated.
PMID- 27612466
TI - A randomised, placebo-controlled trial assessing the efficacy of an oral B group
vitamin in preventing the development of chemotherapy-induced peripheral
neuropathy (CIPN).
AB - INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating
side effect resulting from neurotoxic chemotherapeutic agents. This study aimed
to assess the efficacy and safety of an oral B group vitamin compared to placebo,
in preventing the incidence of CIPN in cancer patients undergoing neurotoxic
chemotherapy. METHODS: A pilot, randomised, placebo-controlled trial was
conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin
or vincristine were invited to participate. A total of 71 participants (female 68
%, male 32 %) were enrolled into the study and randomised to the B group vitamin
(n = 38) arm or placebo (n = 33). The data from 47 participants were eligible for
analysis (B group vitamins n = 27, placebo n = 22). The primary outcome measure
was the total neuropathy score assessed by an independent neurologist. Secondary
outcome measures included serum vitamin B levels, quality of life, pain inventory
and the patient neurotoxicity questionnaires. Outcome measures were conducted at
baseline, 12, 24 and 36 weeks. RESULTS: The total neuropathy score (TNS)
demonstrated that a B group vitamin did not significantly reduce the incidence of
CIPN compared to placebo (p = 0.73). Statistical significance was achieved for
patient perceived sensory peripheral neuropathy (12 weeks p = 0.03; 24 weeks p =
0.005; 36 weeks p = 0.021). The risk estimate for the Patient Neurotoxicity
Questionnaire (PNQ) was also statistically significant (OR = 5.78, 95 % CI = 1.63
20.5). The European Organisation of Research and Treatment of Cancer (EORTC)
quality of life, total pain score and pain interference showed no significance (p
= 0.46, p = 0.9, p = 0.37 respectively). A trend was observed indicating that
vitamin B12 may reduce the onset and severity of CIPN. CONCLUSION: An oral B
group vitamin as an adjunct to neurotoxic chemotherapy regimens was not superior
to placebo (p > 0.05) for the prevention of CIPN. Patients taking the B group
vitamin perceived a reduction in sensory peripheral neuropathy in the PNQ.
Moreover, a robust clinical study is warranted given that vitamin B12 may show
potential in reducing the onset and severity of CIPN. Trial number:
ACTRN12611000078954 Protocol number: UH2010000749.
PMID- 27612467
TI - Behavioral Health Treatment Receipt Among a Community Sample of Young Adult
Veterans.
AB - Young adult veterans are at risk for behavioral health problems such as
depression, posttraumatic stress disorder (PTSD), and substance misuse. Despite
this, studies of veterans within the Veterans Affairs Healthcare System (VA)
indicate that about half of those warranting treatment receive it in any form,
with few receiving an adequate dose of care. For this study, the behavioral
health screening status and behavioral health usage (including care outside of VA
settings) among a community sample of 812 young adult veterans recruited from the
Internet is described. Although approximately 70% of the sample screened positive
for behavioral health problems, only one fifth to three fifths of those screening
positive reported any mental health or substance use treatment in the past year,
with one third or less receiving a dose of minimally adequate psychotherapy or
psychotropic care. Findings expand on prior work and suggest that more effort is
necessary to engage young veterans in behavioral health services.
PMID- 27612469
TI - [Radical cystectomy vs. chemoradiation for the treatment of T2-4a N0 M0 bladder
cancer].
PMID- 27612468
TI - Health Status and Social Characteristics Among the Uninsured Using a Mental
Health Free Clinic.
PMID- 27612470
TI - Effectiveness of acellular pertussis vaccination during childhood (<7 years of
age) for preventing pertussis in household contacts 1-9 years old in Catalonia
and Navarra (Spain).
AB - Pertussis vaccination with 4-5 doses of acellular vaccines is recommended in
Spain to all children at 2 months to 6 years of age. The effectiveness of the
acellular pertussis vaccination was assessed in this study by comparing the
incidence of secondary pertussis in vaccinated (4-5 doses) and unvaccinated or
partially vaccinated (0-3 doses) household contacts 1-9 years old of confirmed
cases of pertussis in Spain in 2012-13. Eighty-five percent of contacts had been
vaccinated with 4-5 doses of acellular pertussis vaccines. During the 2-year
study period, 64 cases of secondary pertussis were detected among 405 household
contacts 1-9 years old: 47 among vaccinated and 17 among unvaccinated or
partially vaccinated contacts. The effectiveness for preventing secondary
pertussis, calculated as 1 minus the relative risk (RR) of secondary pertussis in
vaccinated vs. unvaccinated/partially vaccinated contacts, was 50 % [95 %
confidence interval (CI): 19-69 %, p < 0.01] when household contacts were
vaccinated using DTaP, Tdap, hexavalent or heptavalent vaccines, and it was 51.3
% (95 % CI: 21-70 %, p < 0.01) when they were vaccinated using DTaP or TdaP
vaccines. The effectiveness adjusted for age, sex, pertussis chemotherapy and
type of household contact was 58.6 % (95 % CI: 17-79 %, p < 0.05) when contacts
were vaccinated using available acellular vaccines, and it was 59.6 % (95 % CI:
18-80 %, p < 0.01) when they were vaccinated using DTaP vaccines. Acellular
pertussis vaccination during childhood was effective for preventing secondary
pertussis in household contacts 1-9 years old of pertussis cases in Catalonia and
Navarra, Spain.
PMID- 27612471
TI - Adverse effects of isolation: a prospective matched cohort study including 90
direct interviews of hospitalized patients in a French University Hospital.
AB - Isolation precautions in patients with multi-drug resistant bacteria or other
communicable infectious agents can be associated with adverse effects. The aim of
this study was to assess satisfaction and psychological impact of patients
hospitalized with isolation precautions in comparison with controls. An
observational prospective cohort study was performed in five different medical
and surgical departments in a 3,000-bed university hospital in Western France
between March and July 2012. Different scales were used to assess patient
satisfaction (qualitative scale) and anxiety (Spielberger scale), including 30
patients with isolation precautions and 60 matched patients without isolation
precautions over 45-hour interviews. Cases were significantly less satisfied than
controls for healthcare workers (HCW) assistance in activities of daily life (p <
0.001), availability and relationships (17 % vs 5 %, p = 0.05 and 10 % vs 0%, p =
0.02, respectively). Sixty-seven percent of patients with isolation precautions
were not satisfied about the quality of the information related to their
infectious status control measures. The median score [range] of anxiety
significantly was higher in patients with isolation precautions (52 [20-56] vs 31
[23-73], p <0.001). Isolation precautions may have negative psychological
effects, leading to anxiety, and may compromise patient satisfaction according to
the availability and relationship with HCW. Professionals should be aware of
adverse effects of isolation and inform patients more actively with regard to
their infectious status and precautions.
PMID- 27612472
TI - Investigations of putative reproductive toxicity of low-dose exposures to
vinclozolin in Wistar rats.
AB - The current investigation examines whether the fungicide vinclozolin, which has
an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis
at very low doses. The data generated clarify whether a non-monotonic dose
response relationship exists to enhance the current debate about the regulation
of endocrine disruptors. Moreover, it is part of a series of investigations
assessing the dose-response relationship of single and combined administration of
anti-androgenic substances. A pre-postnatal in vivo study design was chosen which
was compliant with regulatory testing protocols. The test design was improved by
additional endpoints addressing hormone levels, morphology and histopathological
examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the
current NOAEL (4 mg/kg bw/d), and a dose close to the "ADI" (0.005 mg/kg bw/d)
for the detection of a possible non-monotonic dose-response curve. Anti
androgenic changes were observable at the effect level but not at lower
exposures. Nipple/areola counts appeared to be the most sensitive measure of
effect, followed by male sex organ weights at sexual maturation, and finally
gross and histopathological findings. The results indicate the absence of
evidence for effects at low or very low dose levels. A non-monotonic dose
response relationship was not evident.
PMID- 27612473
TI - Normal Variants in Echocardiography.
AB - Echocardiography is a powerful and convenient tool used routinely in the cardiac
evaluation of many patients. Improved resolution and visualization of cardiac
anatomy has led to the discovery of many normal variant structures that have no
known pathologic consequence. Importantly, these findings may masquerade as
pathology prompting unnecessary further evaluation at the expense of anxiety,
cost, or potential harm. This review provides an updated and comprehensive
collection of normal anatomic variants on both transthoracic and transesophageal
imaging.
PMID- 27612474
TI - Integrating Biomarkers and Imaging for Cardiovascular Disease Risk Assessment in
Diabetes.
AB - Cardiovascular disease (CVD) risk assessment has changed substantially in recent
years. While older guidelines considered diabetes a coronary disease risk
equivalent, more recent guidelines recommend risk stratification on the basis of
global risk scoring to target intensity of therapy. While patients with diabetes
as a whole are at greater risk for CVD events, these patients may also benefit
from risk stratification based on circulating biomarkers like high-sensitivity C
reactive protein, high-sensitivity cardiac troponin T, and N-terminal pro-B-type
natriuretic peptide, as well as newer imaging modalities (coronary artery
calcium, carotid intima-media thickness, and myocardial perfusion imaging). The
addition of these CVD risk assessment modalities could play an important role for
deciding how aggressive a physician should be with pharmacological therapy. Here,
we discuss many of the current recommendations of CVD risk assessment in patients
with diabetes including newer modalities for CVD risk assessment.
PMID- 27612476
TI - [Autologous hematopoietic stem cell transplantation in systemic lupus
erythematosus].
AB - Although the treatment options for systemic lupus erythematosus (SLE) have
significantly improved over the past years through the introduction of novel
targeted biologic therapies, there are still some patients who suffer from
refractory and potentially life-threatening courses of the disease. For these
patients autologous hematopoietic stem cell transplantation (ASCT) after
immunoablative chemotherapy provides a promising treatment option with curative
potential. Based on preclinical models, ASCT was first introduced in 1996 and has
since been carried out in approximately 300 patients worldwide. Clinical study
results confirmed a disease-free survival in approximately 50 % of patients after
5 years despite termination of immunosuppressive treatment. By careful patient
selection and improved anti-infection prophylaxis during stem cell therapy,
transplantation-associated mortality could be reduced from an initial 13 % to
currently an average of 6 %. Meanwhile, mechanistic studies have provided proof
of concept that ASCT not only exerts intensified immunosuppressive effects but is
also associated with fundamental qualitative changes of the immune system that
may rewire a chronic autoimmune system into a naive and self-tolerant state: in
other words immune reset. Overall, ASCT for SLE is still reserved for patients
who do not sufficiently respond to standard therapy. Treatment should be carried
out in close cooperation with centers specializing in hematology and only within
the framework of clinical studies.
PMID- 27612475
TI - The Protective Role of Positive Well-Being in Cardiovascular Disease: Review of
Current Evidence, Mechanisms, and Clinical Implications.
AB - Positive psychological aspects of well-being-including positive emotions,
optimism, and life satisfaction-are increasingly considered to have protective
roles for cardiovascular disease (CVD) and longevity. A rapidly-growing body of
literature has linked positive well-being with better cardiovascular health,
lower incidence of CVD in healthy populations, and reduced risk of adverse
outcomes in patients with existing CVD. This review first examines evidence on
the associations of positive well-being with CVD and mortality, focusing on
recent epidemiological research as well as inconsistent findings. Next, an
overview is provided of putative biological, behavioral, and stress-buffering
mechanisms that may underlie the relationship between positive well-being and
cardiovascular health. Key areas for future inquiry are discussed, in addition to
emerging developments that capitalize on technological and methodological
advancements. Promising initial results from randomized controlled trials suggest
that efforts to target positive well-being may serve as valuable components of
broader CVD management programs.
PMID- 27612477
TI - Cultural Adaptation, Parenting and Child Mental Health Among English Speaking
Asian American Immigrant Families.
AB - Contrary to the "model minority" myth, Asian American children, especially those
from low-income immigrant families, are at risk for both behavioral and emotional
problems early in life. Little is known, however, about the underlying
developmental mechanisms placing Asian American children at risk, including the
role of cultural adaptation and parenting. This study examined cultural
adaptation, parenting practices and culture related parenting values and child
mental health in a sample of 157 English speaking Asian American immigrant
families of children enrolled in early childhood education programs in low
income, urban neighborhoods. Overall, cultural adaptation and parenting cultural
values and behaviors were related to aspects of child mental health in meaningful
ways. Parents' cultural value of independence appears to be especially salient
(e.g., negatively related to behavior problems and positively related to adaptive
behavior) and significantly mediates the link between cultural adaptation and
adaptive behavior. Study findings have implications for supporting Asian American
immigrant families to promote their young children's mental health.
PMID- 27612478
TI - Role of miRNA dynamics and cytokine profile in governing CD44v6/Nanog/PTEN axis
in oral cancer: modulating the master regulators.
AB - Late diagnosis, low therapeutic response, and metastasis are accountable for poor
5-year survival rate of OSCC. These failures are attributed to the existence of
"cancer stem cell (CSC)" subpopulation. Hence, it is necessary to identify and
understand the mechanism of CSCs in tumor development, metastasis, and
chemotherapeutic response. Propelling evidences suggest that microRNA (miRNA)
mediated regulation and cytokines of tumor microenvironment have the ability to
modulate CSC signalling pathway; however, their exact mechanism needs to be
elucidated. Thus, in this study, we characterized CSC markers and highlighted the
miRNA dynamics and cytokine profile regulating these CSCs in a pathway-dependent
manner. Our results demonstrated CD44+ subpopulation as tumor-initiating cells
with self-renewal capability, tumorigenic growth potential and intrinsic
chemoresistance. These tumors exhibited increased expression of CSC markers
(CD44v3, CD44v6, Nanog, and Bmi1) and significantly reduced expression of PTEN
and ATM in OSCC patients. Pathway analysis of these CSC markers demonstrated a
prospective pathway regulated by miRNA and cytokine network. On analyzing these
modulators, we observed decreased expression of miRNA542-3p, miRNA34a and miRNA9,
and significant upregulation of miRNA21, thus forming an unexplored axis.
Cytokine profiling revealed significantly increased levels of IL-6 and IL-8
compared to normals and demonstrated their strong association with CD44v6.
Collectively, this study indicates that miR5423p and miR34a targets the CD44v6
Nanog-PTEN axis, thus playing a vital role in regulating the CSC properties.
Furthermore, we speculate an impinging role of cytokines IL-6 and IL-8 in
regulating this CSC-mediated pathway which can have prognostic and therapeutic
implications.
PMID- 27612479
TI - Upregulation of annexin A1 expression by butyrate in human melanoma cells induces
invasion by inhibiting E-cadherin expression.
AB - Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis
of epithelial cancer cells. Butyrate, which is produced from dietary fiber by
colonic bacterial fermentation, has been reported to influence EMT. However, some
studies have reported that butyrate promotes EMT, while others have reported an
inhibitory effect. To clarify these controversial results, it is necessary to
elucidate the mechanism by which butyrate can influence EMT. In this study, we
examined the potential role of annexin A1 (ANXA1), which was previously reported
to promote EMT in breast cancer cells, as a mediator of EMT regulation by
butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive
melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less
invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression
and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1
expression using specific small interfering RNAs in butyrate-treated SK-MEL-5
cells resulted in increased expression of the epithelial marker E-cadherin and
decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression
of the E-cadherin. Collectively, these results indicate that butyrate induces the
expression of ANXA1 in human melanoma cells, which then promotes invasion through
activating the EMT signaling pathway.
PMID- 27612481
TI - Expert panel recommends that the US cancer "moonshot" focuses on 10 areas.
PMID- 27612480
TI - Signatures of prostate-derived Ets factor (PDEF) in cancer.
AB - The Ets proteins are a family of transcription factors characterized by an
evolutionarily conserved DNA-binding domain and have diverse biological functions
including tumor suppressor as well as tumor promoter functions. They are
regulated via a complex and diverse number of mechanisms and control key cellular
processes. Prostate-derived Ets transcription factor (PDEF), a unique member of
the ETS family, is present in tissues with high epithelial content are hormone
regulated, such as prostate, breast, salivary glands, ovaries, colon, airways,
and stomach tissues. PDEF (prostate-derived Ets factor) is also referred to as
SPDEF (SAM pointed domain containing Ets transcription factor), PSE (mouse
homolog), or hPSE (human PSE) in the literature and is the sole member of the
PDEF ETS sub-family. The role of PDEF in cancer development is still not fully
elucidated though. The present article focuses on the key findings about the
PDEF's biological functions, interacting proteins, and its target genes. There is
a strong urge to focus on the clinical studies in larger cohort, which elucidate
the regulation of PDEF and its target genes, to determine the potential of PDEF
as biomarker. Based on the studies discussed in the present article, one can
anticipate that PDEF offers a great potential for developing therapeutics against
cancer.
PMID- 27612482
TI - Removal of Tenon fortified by conjunctival-limbal autograft in treatment of
pterygium.
AB - PURPOSE: To describe a simple and effective technique for the prevention of
pterygium recurrence. METHODS: This is a retrospective consecutive single-center
case series with recurrence rate as the main outcome measure. Dissection of the
conjunctiva, the Tenon's layer, and the sclera was continued up to the insertion
of medial rectus. The exposed Tenon's layer was excised for 2 to 3 mm. The entire
free edges of the conjunctiva was tacked firmly to the sclera. The conjunctival
limbal graft was sutured firmly to the sclera, recipient limbus, and to the
conjunctiva incorporating the reciprocal edges. RESULTS: We report findings in a
total of 36 patients, with 20 (%55.5) males and 16 (%44.4) females. Median age of
the patients was 44.5 years (range 16-80). The mean follow-up period was 23.1 +/-
6.5 months. The mean size of pterygium in mm length was 3.8 +/- 0.7. Recurrence
did not occur in any patient. Diplopia was not reported by any patients.
CONCLUSIONS: Conjunctival-limbal autograft combining with selective exicison of
Tenon's layer but without damage to any essential tissue such as the semilunar
fold or Tenon's capsule pulley is a relatively simple and effective procedure.
PMID- 27612484
TI - Capsule Commentary on Young et al., Internal Medicine Residents' Perceived
Responsibility for Patients at Hospital Discharge: A National Survey.
PMID- 27612483
TI - In vivo monitoring of transfected DNA, gene expression kinetics, and cellular
immune responses in mice immunized with a human NIS gene-expressing plasmid.
AB - In assessing the effectiveness of DNA vaccines, it is important to monitor: (1)
the kinetics of target gene expression in vivo; and (2) the movement of cells
that become transfected with the plasmid DNA used in the immunization of a
subject. In this study, we used, as a visual imaging marker, expression of the
transfected human sodium/iodide symporter (hNIS) gene, which enhances
intracellular radio-pertechnetate (TcO4-) accumulation. After intradermal (i.d.)
and systemic injection of mice with pcDNA-hNIS and radioactive Technetium-99m (Tc
99m), respectively, whole-body images were obtained by nuclear scintigraphy. The
migration of mice cells transfected with the hNIS gene was monitored over a 2
week period by gamma-radioactivity counting of isolated cell populations and was
demonstrated in peripheral lymphoid tissues, especially in the draining lymph
nodes (dLNs). Beginning at 24 h after DNA inoculation and continuing for the 2
week monitoring period, hNIS-expressing cells were observed specifically in the T
cell-rich zones of the paracortical area of the dLNs. Over the same time period,
high levels of INF-gamma-secreting CD8 T-cells were found in the dLNs of the
pcDNA-hNIS immunized mice. Tumor growth was also significantly retarded in the
mice that received hNIS DNA immunization followed by inoculation with CT26
colorectal adenocarcinoma cells that had been transfected with the rat NIS gene
(rNIS), which is 93% homologous to the hNIS gene. In conclusion, mouse cells
transfected with hNIS DNA after i.d. immunization were found to traffic to the
dLNs, and hNIS gene expression in these cells continued for at least 2 weeks post
immunization. Furthermore, sequential presentation of NIS DNA to T-cells by
migratory antigen presenting cells could induce NIS DNA-specific Th1 immune
responses and thus retard the growth of NIS-expressing tumors.
PMID- 27612485
TI - Carotid Cavernous Fistula.
PMID- 27612486
TI - Do Work Condition Interventions Affect Quality and Errors in Primary Care?
Results from the Healthy Work Place Study.
AB - BACKGROUND: While primary care work conditions are associated with adverse
clinician outcomes, little is known about the effect of work condition
interventions on quality or safety. DESIGN: A cluster randomized controlled trial
of 34 clinics in the upper Midwest and New York City. PARTICIPANTS: Primary care
clinicians and their diabetic and hypertensive patients. INTERVENTIONS: Quality
improvement projects to improve communication between providers, workflow design,
and chronic disease management. Intervention clinics received brief summaries of
their clinician and patient outcome data at baseline. MAIN MEASURES: We measured
work conditions and clinician and patient outcomes both at baseline and 6-12
months post-intervention. Multilevel regression analyses assessed the impact of
work condition changes on outcomes. Subgroup analyses assessed impact by
intervention category. KEY RESULTS: There were no significant differences in
error reduction (19 % vs. 11 %, OR of improvement 1.84, 95 % CI 0.70, 4.82, p =
0.21) or quality of care improvement (19 % improved vs. 44 %, OR 0.62, 95 % CI
0.58, 1.21, p = 0.42) between intervention and control clinics. The conceptual
model linking work conditions, provider outcomes, and error reduction showed
significant relationships between work conditions and provider outcomes (p <=
0.001) and a trend toward a reduced error rate in providers with lower burnout
(OR 1.44, 95 % CI 0.94, 2.23, p = 0.09). LIMITATIONS: Few quality metrics, short
time span, fewer clinicians recruited than anticipated. CONCLUSIONS: Work-life
interventions improving clinician satisfaction and well-being do not necessarily
reduce errors or improve quality. Longer, more focused interventions may be
needed to produce meaningful improvements in patient care. CLINICAL TRIAL
REGISTRATION NUMBER: ClinicalTrials.gov # NCT02542995.
PMID- 27612488
TI - Real-life chromoendoscopy for neoplasia detection and characterisation in long
standing IBD.
AB - OBJECTIVE: Outside clinical trials, the effectiveness of chromoendoscopy (CE) for
long-standing IBD surveillance is controversial. We aimed to assess the
effectiveness of CE for neoplasia detection and characterisation, in real-life.
DESIGN: From June 2012 to 2014, patients with IBD were prospectively included in
a multicentre cohort study. Each colonic segment was evaluated with white light
followed by 0.4% indigo carmine CE. Specific lesions' features were recorded.
Optical diagnosis was assessed. Dysplasia detection rate between expert and non
expert endoscopists and learning curve were ascertained. RESULTS: Ninety-four
(15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and
503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female;
mean disease duration: 17 years). Colonoscopies were performed with standard
definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white
light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield
for dysplasia was comparable between standard definition and high definition
(51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert
and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was
observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and
negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and
94%, respectively. Endoscopic characteristics predictive of dysplasia were:
proximal location, loss of innominate lines, polypoid morphology and Kudo pit
pattern III-V. CONCLUSIONS: CE presents a high diagnostic yield for neoplasia
detection, irrespectively of the technology and experience available in any
centre. In vivo, CE optical diagnosis is highly accurate for ruling out
dysplasia, especially in expert hands. Lesion characteristics can aid the
endoscopist for in situ therapeutic decisions. TRIAL REGISTRATION NUMBER:
NCT02543762.
PMID- 27612489
TI - Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the
Pediatric Age Spectrum.
AB - Sudden infant death syndrome (SIDS) and sudden unexplained death in childhood
(SUDC) are defined as sudden death in a child remaining unexplained despite
autopsy and death scene investigation. They are distinguished from each other by
age criteria, i.e. with SIDS under 1 year and SUDC over 1 year. Our separate
studies of SIDS and SUDC provide evidence of shared hippocampal abnormalities,
specifically focal dentate bilamination, a lesion classically associated with
temporal lobe epilepsy, across the 2 groups. In this study, we characterized the
clinicopathologic features in a retrospective case series of 32 children with
sudden death and hippocampal formation (HF) maldevelopment. The greatest
frequency of deaths was between 3 weeks and 3 years (81%, 26/32). Dentate
anomalies were found across the pediatric age spectrum, supporting a common
vulnerability that defies the 1-year age cutoff between SIDS and SUDC. Twelve
cases (38%) had seizures, including 7 only with febrile seizures. Subicular
anomalies were found in cases over 1 year of age and were associated with
increased risk of febrile seizures. Sudden death associated with HF
maldevelopment reflects a complex interaction of intrinsic and extrinsic factors
that lead to death at different pediatric ages, and may be analogous to sudden
unexplained death in epilepsy.
PMID- 27612487
TI - Patient and Partner Feedback Reports to Improve Statin Medication Adherence: A
Randomized Control Trial.
AB - BACKGROUND: Simple nudges such as reminders and feedback reports to either a
patient or a partner may facilitate improved medication adherence. OBJECTIVE: To
test the impact of a pill bottle used to monitor adherence, deliver a daily
alarm, and generate weekly medication adherence feedback reports on statin
adherence. DESIGN: Three-month, three-arm randomized clinical trial
(ClinicalTrials.gov identifier: NCT02480530). PARTICIPANTS: One hundred and
twenty-six veterans with known coronary artery disease and poor adherence
(medication possession ratio <80 %). INTERVENTION: Patients were randomized to
one of three groups: (1) a control group (n = 36) that received a pill-monitoring
device with no alarms or feedback; (2) an individual feedback group (n = 36) that
received a daily alarm and a weekly medication adherence feedback report; and (3)
a partner feedback group (n = 54) that received an alarm and a weekly feedback
report that was shared with a friend, family member, or a peer. The intervention
continued for 3 months, and participants were followed for an additional 3 months
after the intervention period. MAIN MEASURES: Adherence as measured by pill
bottle. Secondary outcomes included change in LDL (mg/dl), patient activation,
and social support. KEY RESULTS: During the 3-month intervention period,
medication adherence was higher in both feedback arms than in the control arm
(individual feedback group 89 %, partner feedback group 86 %, control group 67 %;
p < 0.001 and = 0.001). At 6 months, there was no difference in medication
adherence between either of the feedback groups and the control (individual
feedback 60 %, partner feedback 52 %, control group 54 %; p = 0.75 and 0.97).
CONCLUSIONS: Daily alarms combined with individual or partner feedback reports
improved statin medication adherence. While neither an individual feedback nor
partner feedback strategy created a sustainable medication adherence habit, the
intervention itself is relatively easy to implement and low cost.
PMID- 27612490
TI - Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met
Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR
Mutation.
AB - Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung
cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent
EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that
Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of
EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring
15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing
concentrations of the Met-TKI PHA665752 and 1 MUmol/L gefitinib for 1 year; three
resistant clones were established via Met amplification. The three dual
resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and
DR6, respectively) exhibited different mechanisms for evading both EGFR and Met
inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a
Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2
and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated
to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by
overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified
by association with HSP90, which protected Met from degradation and induced SET
and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the
first report describing the acquisition of dual resistance mechanisms in NSCLC
harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous
EGFR-TKI treatment. These results might inform the development of more effective
therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040-54.
(c)2016 AACR.
PMID- 27612491
TI - Tiotropium in the add-on treatment of asthma in adults: clinical trial evidence
and experience.
AB - Asthma is a chronic inflammatory airway disease, and its treatment is frequently
challenging despite detailed national and international guidelines. While basic
anti-inflammatory therapy usually consists of inhaled corticosteroids in doses
adapted to the asthma severity, add-on treatment with bronchodilators is
essential in more severe asthma. Only recently, the long-acting anticholinergic
tiotropium was introduced into the GINA guidelines. This review reports on the
studies that have been performed with tiotropium in adult asthmatic patients.
Following early proof-of-concept studies, several studies with tiotropium as an
add-on therapy to inhaled corticosteroids (ICS), with or without a long-acting
beta agonist (LABA), demonstrated convincing clinical benefit for patients.
Important lung function parameters and quality of life scores significantly
improved shortly after onset of the add-on therapy with tiotropium, and some
studies even demonstrated non-inferiority against salmeterol. All studies
reported an excellent safety profile of tiotropium. The still growing body of
tiotropium studies, both in adults and children, will help to identify the
position of tiotropium in future asthma guidelines and might also indicate which
patients benefit most from an add-on therapy with tiotropium.
PMID- 27612493
TI - Novel groups of cyanobacterial podovirus DNA polymerase (pol) genes exist in
paddy waters in northeast China.
AB - In this study, we surveyed cyanopodovirus DNA polymerase (pol) sequences in paddy
waters using the culture-independent PCR and Sanger sequencing methods. Four
paddy waters generated from a pot experiment with different soil types collected
from op E: n paddy fields in northeast China were used in this study. A total of
438 DNA pol clones were identified as cyanopodoviruses. The clones from the paddy
waters formed nine unique groups of cyanopodoviruses either exclusively or with
clones from East Lake in China (subclusters alpha-1 to alpha-8 and cluster beta).
None of the clones from open oceans or coastal waters fell into these unique
groups. Additionally, the distribution proportions of the clones into different
cyanopodovirus groups varied among paddy water samples, which suggested that the
cyanopodovirus compositions were spatially distributed in the paddy fields. The
comparison of clone libraries in different studies indicated that the diversity
of cyanopodoviruses in paddy waters was comparable to the diversity in the open
oceans but was less than the diversity in the coastal estuary of Chesapeake Bay.
Non-metric multidimensional scaling analysis indicated that the cyanopodovirus
communities in paddy waters were similar to those in lake freshwater but distinct
from the communities in marine and coastal waters.
PMID- 27612492
TI - The clinical profile of benralizumab in the management of severe eosinophilic
asthma.
AB - Despite several therapeutic choices, 10-20% of patients with severe uncontrolled
asthma do not respond to maximal best standard treatments, leading to a
healthcare expenditure of up to 80% of overall costs for asthma. Today, there are
new important therapeutic strategies, both pharmacological and interventional,
that can result in improvement of severe asthma management, such as omalizumab,
bronchial thermoplasty and other biological drugs, for example, mepolizumab,
reslizumab and benralizumab. The availability of these new treatments and the
increasing knowledge of the different asthmatic phenotypes and endotypes makes
correct patient selection increasingly complex and important. In this article, we
discuss the features of benralizumab compared with other anti-interleukin-5
biologics and omalizumab, the identification of appropriate patients, the safety
profile and future developments.
PMID- 27612494
TI - Evolution of prokaryotic respiratory molybdoenzymes and the frequency of their
genomic co-occurrence.
AB - Molybdoenzymes are an ancient protein family found in phylogenetically and
ecologically diverse prokaryotes. Under anaerobic conditions, respiratory
molybdoenzymes catalyze redox reactions that transfer electrons to a variety of
substrates that act as terminal electron acceptors for energy generation. Here,
we used probe sequences to conduct an extensive genomic survey and phylogenetic
inference for NarG, DmsA, TorA and nine other respiratory molybdoenzyme
subfamilies. Our analysis demonstrates their abundance in 60% of prokaryotic
phyla. In contrast to many other autonomic genetic units in prokaryotes, the
major route of evolution of their predominant subfamilies is vertical gene
transfer, gene duplication and divergence. Our results show the robustness of
genomic co-occurrence of respiratory molybdoenzymes genes, found in the majority
of studied species, for most of the enzyme subfamilies. Genomes which encode for
multiple respiratory molybdoenzymes are also enriched in genes regulating
replication, recombination and mobility of genetic elements. Respiratory
molybdoenzymes were found in prokaryotes associated with diverse environments
occupying terrestrial, aquatic, food and host-related habitats, emphasizing their
essential role in adaptation of prokaryotes to changing environments.
Interestingly, host-associated prokaryotes such as human pathogens more
frequently carry multiple respiratory molybdoenzyme genes compared with non-host
associated prokaryotes, highlighting the importance of metabolic flexibility in
host-microbiome environments.
PMID- 27612495
TI - Long-term CO2 injection and its impact on near-surface soil microbiology.
AB - Impacts of long-term CO2 exposure on environmental processes and microbial
populations of near-surface soils are poorly understood. This near-surface long
term CO2 injection study demonstrated that soil microbiology and geochemistry is
influenced more by seasonal parameters than elevated CO2 Soil samples were taken
during a 3-year field experiment including sampling campaigns before, during and
after 24 months of continuous CO2 injection. CO2 concentrations within CO2
injected plots increased up to 23% during the injection period. No CO2 impacts on
geochemistry were detected over time. In addition, CO2-exposed samples did not
show significant changes in microbial CO2 and CH4 turnover rates compared to
reference samples. Likewise, no significant CO2-induced variations were detected
for the abundance of Bacteria, Archaea (16S rDNA) and gene copy numbers of the
mcrA gene, Crenarchaeota and amoA gene. The majority (75%-95%) of the bacterial
sequences were assigned to five phyla: Firmicutes, Proteobacteria,
Actinobacteria, Acidobacteria and Bacteroidetes The majority of the archaeal
sequences (85%-100%) were assigned to the thaumarchaeotal cluster I.1b (soil
group). Univariate and multivariate statistical as well as principal component
analyses showed no significant CO2-induced variation. Instead, seasonal impacts
especially temperature and precipitation were detected.
PMID- 27612497
TI - Bacillus thuringiensis Cyt2Aa2 toxin disrupts cell membranes by forming large
protein aggregates.
AB - Bacillus thuringiensis (Bt) Cyt2Aa2 showed toxicity against Dipteran insect
larvae and in vitro lysis activity on several cells. It has potential
applications in the biological control of insect larvae. Although pore-forming
and/or detergent-like mechanisms were proposed, the mechanism underlying
cytolytic activity remains unclear. Analysis of the haemolytic activity of
Cyt2Aa2 with osmotic stabilizers revealed partial toxin inhibition, suggesting a
distinctive mechanism from the putative pore formation model. Membrane
permeability was studied using fluorescent dye entrapped in large unilamellar
vesicles (LUVs) at various protein/lipid molar ratios. Binding of Cyt2Aa2 monomer
to the lipid membrane did not disturb membrane integrity until the critical
protein/lipid molar ratio was reached, when Cyt2Aa2 complexes and cytolytic
activity were detected. The complexes are large aggregates that appeared as a
ladder when separated by agarose gel electrophoresis. Interaction of Cyt2Aa2 with
Aedes albopictus cells was investigated by confocal microscopy and total internal
reflection fluorescent microscopy (TIRF). The results showed that Cyt2Aa2 binds
on the cell membrane at an early stage without cell membrane disruption. Protein
aggregation on the cell membrane was detected later which coincided with cell
swelling. Cyt2Aa2 aggregations on supported lipid bilayers (SLBs) were visualized
by AFM. The AFM topographic images revealed Cyt2Aa2 aggregates on the lipid
bilayer at low protein concentration and subsequently disrupts the lipid bilayer
by forming a lesion as the protein concentration increased. These results
supported the mechanism whereby Cyt2Aa2 binds and aggregates on the lipid
membrane leading to the formation of non-specific hole and disruption of the cell
membrane.
PMID- 27612498
TI - The influence of glycation on a high pressure denaturation of ubiquitin.
AB - The combination of deuterium-hydrogen exchange (DHX) and mass spectrometry (MS)
can be used for studying a high pressure denaturation (HPD) of proteins. Herein
we present the results of investigations of the influence of glycation on the HPD
of ubiquitin. Application of various values of pressure causes different degrees
of protein unfolding, resulting in molecules with a different number of protons
available for exchange with deuterons. The dependence of this number on pressure
gives information on the denaturation state of a protein. On the basis of the
obtained results we can conclude that increasing number of fructosamine moieties
in ubiquitin decreases the pressure required for its denaturation. It suggests
that glycation moderately decreases the protein stability. The present study is
the first example of application of hydrogen-deuterium exchange as a method of
investigating the influence of posttranslational modification of protein on the
HPD.
PMID- 27612496
TI - Differential renal effects of candesartan at high and ultra-high doses in
diabetic mice-potential role of the ACE2/AT2R/Mas axis.
AB - High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in
diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra
high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2
(ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the
renin-angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP),
albuminuria and expression/activity of RAS components were assessed in diabetic
db/db and control db/+ mice treated with increasing candesartan doses
(intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4
weeks). Lower doses candesartan did not influence SBP, but ultra-high doses
reduced SBP in both groups. Plasma glucose and albuminuria were increased in
db/db compared with db/+ mice. In diabetic mice treated with intermediate dose
candesartan, renal tubular damage and albuminuria were ameliorated and expression
of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated
with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection.
Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal
injury with increased renal ERK1/2 activation and exaggerated fibronectin
expression in db/db mice. Our study demonstrates dose-related effects of
candesartan in diabetic nephropathy: intermediate-high dose candesartan is
renoprotective, whereas ultra-high dose candesartan induces renal damage.
Molecular processes associated with these effects involve differential modulation
of the ACE2/AT2R/Mas axis: intermediate-high dose candesartan up-regulating RAS
protective components and attenuating pro-fibrotic processes, and ultra-high
doses having opposite effects. These findings suggest novel mechanisms through
the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy.
Our findings also highlight potential injurious renal effects of ultra-high dose
candesartan in diabetes.
PMID- 27612499
TI - Diabetes Is Associated With Decreased Limb Survival in Patients With Critical
Limb Ischemia: Pooled Data From Two Randomized Controlled Trials.
AB - OBJECTIVE: Although never assessed prospectively, diabetes mellitus (DM) is
assumed to negatively affect the outcomes of critical limb ischemia (CLI). DM was
highly prevalent in two recently conducted randomized controlled trials in CLI
patients, the PADI (Percutaneous Transluminal Balloon Angioplasty [PTA] and Drug
Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia) and JUVENTAS
(Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-Arterial
Supplementation) trials. To determine the implications of DM in a population of
patients with infrapopliteal CLI, clinical outcomes were compared in patients
with and without DM. RESEARCH DESIGN AND METHODS: Individual data from patients
with CLI (Rutherford category >=4) were pooled. Patients were considered to have
DM when this diagnosis was reported in the hospital electronic medical records.
Rates of major amputation (above ankle level) and major events (major amputation
or death) were compared between CLI patients with and without DM. Hazard ratios
(HRs) were calculated. RESULTS: Of a total of 281 patients, DM was present in
49.1%. The major amputation rate at 5 years of follow-up was higher in patients
with DM than in patients without DM (34.1% vs. 20.4%, P = 0.015). The major event
and death rate did not differ. The unadjusted HR of DM for the major amputation
risk was 1.87 (95% CI 1.12-3.12). Model factors with significant HRs in the
multivariate analysis were baseline Rutherford category (HR 1.95; 95% CI 1.24
3.06) and ankle-brachial index (ABI) >1.4 (HR 2.78; 95% CI 1.37-5.64).
CONCLUSIONS: CLI patients with DM are at a significantly higher risk of major
amputation than CLI patients without DM. This increased risk is associated with a
higher prevalence of baseline ABI >1.4 and more severe ischemia at initial
presentation in patients with DM.
PMID- 27612500
TI - Home Use of Day-and-Night Hybrid Closed-Loop Insulin Delivery in Suboptimally
Controlled Adolescents With Type 1 Diabetes: A 3-Week, Free-Living, Randomized
Crossover Trial.
AB - OBJECTIVE: This study evaluated the feasibility, safety, and efficacy of day-and
night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes
under free-living conditions. RESEARCH DESIGN AND METHODS: In an open-label
randomized crossover study, 12 suboptimally controlled adolescents on insulin
pump therapy (mean +/- SD age 14.6 +/- 3.1 years; HbA1c 69 +/- 8 mmol/mol [8.5 +/
0.7%]; duration of diabetes 7.8 +/- 3.5 years) underwent two 21-day periods in
which hybrid closed-loop insulin delivery was compared with sensor-augmented
insulin pump therapy in random order. During the closed-loop intervention, a
model predictive algorithm automatically directed insulin delivery between meals
and overnight. Participants used a bolus calculator to administer prandial
boluses. RESULTS: The proportion of time that sensor glucose was in the target
range (3.9-10 mmol/L; primary end point) was increased during the closed-loop
intervention compared with sensor-augmented insulin pump therapy by 18.8 +/- 9.8
percentage points (mean +/- SD; P < 0.001), the mean sensor glucose level was
reduced by 1.8 +/- 1.3 mmol/L (P = 0.001), and the time spent above target was
reduced by 19.3 +/- 11.3 percentage points (P < 0.001). The time spent with
sensor glucose levels below 3.9 mmol/L was low and comparable between
interventions (median difference 0.4 [interquartile range -2.2 to 1.3] percentage
points; P = 0.33). Improved glucose control during closed-loop was associated
with increased variability of basal insulin delivery (P < 0.001) and an increase
in the total daily insulin dose (53.5 [39.5-72.1] vs. 51.5 [37.6-64.3] units/day;
P = 0.006). Participants expressed positive attitudes and experience with the
closed-loop system. CONCLUSIONS: Free-living home use of day-and-night closed
loop in suboptimally controlled adolescents with type 1 diabetes is safe,
feasible, and improves glucose control without increasing the risk of
hypoglycemia. Larger and longer studies are warranted.
PMID- 27612503
TI - Clinicopathological characteristics of oestrogen receptor negative, progesterone
receptor positive breast cancers: re-evaluating subsets within this group.
AB - AIMS: The presence of oestrogen and progesterone receptors (ER, PR) in breast
carcinoma is an important prognostic indicator as well as a predictor of likely
response to hormonal treatment. Current ambiguity surrounds ER-negative (-)/PR
positive (+) breast cancer (BC) as to whether this phenotype exists as a distinct
entity. The independent predictive value of PR for treatment considerations is
also in question, as some investigators believe ER status to be the single most
important therapeutic predictive factor in BC. We undertook this study to
determine the existence of ER(-)/PR(+) BC and the prognostic effect, if any, of
this phenotype. METHODS: We investigated 267 archival documented ER(-)/PR(+) BCs
diagnosed between January 1994 and July 2009. Histological slides were retrieved
and reviewed. Tissue microarrays were constructed by selecting two 1 mm cores of
tumour per case. Repeat immunohistochemistry was performed for confirmation of
the ER(-)/PR(+) status. Clinicopathological parameters including age, ethnicity,
tumour size, histological grade, histological subtype, associated ductal
carcinoma in situ, lymphovascular invasion and lymph node status were evaluated.
RESULTS: On repeat immunohistochemistry, 92 tumours were confirmed as ER(-)/PR(+)
BCs. This phenotype accounted for 1.1% of all BC phenotypes and exhibited
different clinicopathological features and survival outcome when compared with
other phenotypes. ER(-)/PR(+) tumours showed a trend for an early recurrence and
poorer overall survival as compared with the patients with ER(+)/PR(+) tumours
and similar to ER(-)/PR(-) tumours. CONCLUSIONS: Our findings suggest that ER(
)/PR(+) BCs exist, although rare, with distinct pathological and clinical
characteristics from patients with ER(+)/PR(+) BCs.
PMID- 27612502
TI - Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary
Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community
Health Study/Study of Latinos (HCHS/SOL).
AB - OBJECTIVE: Type 2 diabetes mellitus (DM) has been associated with lung
dysfunction, but this association has not been explored in Hispanics/Latinos. The
relation between diabetic nephropathy and lung function and symptoms has not been
explored. RESEARCH DESIGN AND METHODS: The Hispanic Community Health Study/Study
of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited
16,415 participants aged 18-74 years (14,455 with complete data on variables of
interest), between 2008 and 2011 from four U.S. communities through a two-stage
area household probability design. Baseline measurements were used for analyses.
Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea
score were compared between individuals with and without DM, overall, and
stratified by albuminuria. The analyses were performed separately for those with
and without preexisting lung disease (chronic bronchitis, emphysema, asthma).
Linear regression with sampling weights was used for all analyses. RESULTS: Among
Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC
values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1
3.00 [2.96-3.04] vs. 3.10 [3.09-3.11] L, P < 0.01; FVC 3.62 [3.59-3.66] vs. 3.81
[3.79-3.83] L, P < 0.001; dyspnea score 0.60 [0.49-0.71] vs. 0.41 [0.34-0.49], P
< 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P
< 0.001), 6% lower FEV1 (P < 0.001), and 2.5-fold higher dyspnea score (P = 0.04)
than those without DM and with normoalbuminuria. Similar findings but with higher
impairment in FVC were found in Hispanics/Latinos with lung disease. CONCLUSIONS:
Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment
that mirror kidney microangiopathy. The progression of pulmonary impairment in
adults with DM needs to be investigated further.
PMID- 27612501
TI - Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2
Diabetes: A Follow-up Analysis of a Randomized Clinical Trial.
AB - OBJECTIVE: To determine whether early administration of losartan slows
progression of diabetic kidney disease over an extended period. RESEARCH DESIGN
AND METHODS: We conducted a 6-year clinical trial in 169 American Indians with
type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants
were randomly assigned to receive losartan and 85 to placebo. Primary outcome was
a decline in glomerular filtration rate (GFR; iothalamate) to <=60 mL/min or to
half the baseline value in persons who entered with GFR <120 mL/min. At
enrollment, GFR averaged 165 mL/min (interquartile range 49-313 mL/min). During
the trial, nine persons reached the primary outcome with a hazard ratio (HR;
losartan vs. placebo) of 0.50 (95% CI 0.12-1.99). Participants were then followed
posttrial for up to 12 years, with treatment managed outside the study. The
effect of losartan on the primary GFR outcome was then reanalyzed for the entire
study period, including the clinical trial and posttrial follow-up. RESULTS:
After completion of the clinical trial, treatment with renin-angiotensin system
inhibitors was equivalent in both groups. During a median of 13.5 years following
randomization, 29 participants originally assigned to losartan and 35 to placebo
reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44-1.18).
CONCLUSIONS: Long-term risk of GFR decline was not significantly different
between persons randomized to early treatment with losartan and those randomized
to placebo. Accordingly, we found no evidence of an extended benefit of early
losartan treatment on slowing GFR decline in persons with type 2 diabetes.
PMID- 27612505
TI - Tumour cell invasion into blood vessels is significantly related to breast cancer
subtypes and decreased survival.
AB - AIMS: Vascular invasion in breast cancer is associated with increased risk of
recurrence, metastases and death from disease. However, there are few studies
discriminating between blood vessel invasion (BVI) and lymphatic vessel
involvement (LVI). METHODS: A population-based series of 282 breast cancers was
examined (200 screen-detected and 82 interval patients) with respect to BVI and
LVI in addition to basic features and molecular subtypes, using CD31 and D2-40
antibodies. This series is part of the prospective Norwegian Breast Cancer
Screening Program. RESULTS: The frequency of LVI and BVI was 25% and 15%,
respectively. BVI was associated with HER2-positive and basal-like tumours, and
several features of aggressive breast cancer, whereas LVI showed weaker
associations. BVI was the strongest factor to predict interval cancer
presentation. BVI showed significant associations with recurrence-free survival
and disease-specific survival in univariate and multivariate analyses, whereas
LVI was not significant. CONCLUSIONS: Our findings indicate that BVI by tumour
cells is strongly associated with aggressive tumour features including a basal
like phenotype, and BVI was an independent prognostic factor in contrast to what
was found for LVI.
PMID- 27612504
TI - Expression pattern of miR-451 and its target MIF (macrophage migration inhibitory
factor) in colorectal cancer.
AB - AIMS: To investigate the expression pattern of microRNA-451 (miR-451) in patients
with colorectal carcinoma and correlate with the expression of its target gene
MIF (macrophage migration inhibitory factor). METHODS: Matched cancer and non
cancer fresh frozen tissues were prospectively collected from 70 patients (35 men
and 35 women) who underwent resection of colorectal adenocarcinoma. These tissues
collected were extracted for miR and complementary DNA conversion. Then, miR-451
expressions in these tissues were measured by quantitative real-time PCR. The
expression was correlated with clinical and pathological parameters of these
patients. In addition, paraffin blocks of 10 colorectal carcinomas with lowest
expression of miR-451 were used for the study of MIF protein expression by
immunohistochemistry. RESULTS: miR-451 was downregulated in majority of the
colorectal cancer tissues when compared with their matched normal tissues (84.3%,
n=59/70). Downregulation of miR-451 correlates significantly with presence of
coexisting adenoma (91.4%, p=0.025). In addition, persistence of cancer or cancer
recurrence after surgery showed significant correlation with downregulation of
miR-451 (80% vs 0%; p=0.028). There is no significant correlation between miR-451
expression and age, gender of the patients as well as size, grades, pathological
stages, presence of lymphovascular permeation, perineural invasion and
microsatellite instability status of the colorectal carcinoma (p>0.05). Majority
of the cases (80%) with low expression of miR-451 showed high levels of MIF
protein expression confirming the inverse relationship between miR-451 and MIF
expressions. CONCLUSIONS: The results showed that miR-451 could play a role in
development and progression of colorectal cancer and likely by targeting MIF.
PMID- 27612506
TI - Communication During Pediatric Intensive Care Unit Family Conferences: A Pilot
Study of Content, Communication, and Parent Perceptions.
AB - While there is a robust literature describing family conferences (FCs) in adult
intensive care units (ICUs), less information exists about FCs in pediatric ICUs
(PICUs). We conducted a pilot study to describe the focus of discussion,
communication patterns of health care team members (HTMs) and parents, and
parents' perspectives about clinician communication during PICU FCs. We analyzed
data from 22 video- or audiorecorded PICU FCs and post-FC questionnaire responses
from 27 parents involved in 18 FCs. We used the Roter Interaction Analysis System
(RIAS) to describe FC dialogue content. Our questionnaire included the validated
Communication Assessment Tool (CAT). FCs were focused on care planning (n = 5),
decision making (n = 6), and updates (n = 11). Most speech came from HTMs (mean
85%; range, 65-94%). Most HTM utterances involved medical information. Most
parent utterances involved asking for explanations. The mean overall CAT score
was 4.62 (using a 1-5 scale where 5 represents excellent and 1 poor) with a mean
of 73.02% "excellent" responses. Update and care-planning FCs had lower CAT
scores compared to decision-making FCs. The lowest scoring CAT items were
"Involved me in decisions as much as I wanted," "Talked in terms I could
understand," and "Gave me as much information as I wanted." These findings
suggest that while health care providers spend most of their time during FCs
relaying medical information, more attention should be directed at providing
information in an understandable manner. More work is needed to improve
communication when decision making is not the main focus of the FC.
PMID- 27612507
TI - Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy.
AB - As there are no specific non-invasive markers for the diagnosis of tubal ectopic
pregnancy, our objective in the present study was to explore the role of
inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic
pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with
intrauterine abortion and 29 gestational age matched women having normal
intrauterine pregnancy were included in the study. Five millilitre of blood was
collected at the time of admission, serum was separated and stored at -70
degrees C for subsequent analysis of beta hCG, IL-6 and IL-8 levels. The level of
IL-6 was a significant increase in the women with tubal ectopic pregnancy
compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease
significantly in the tubal ectopic pregnancy and in intrauterine abortion
patients when compared with the normal pregnancy group. At the cutoff of 26.48
pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy.
Therefore, it can be concluded that measurement of IL-6 may have relevance in the
diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.
PMID- 27612508
TI - alphaE-catenin-dependent mechanotransduction is essential for proper convergent
extension in zebrafish.
AB - Cadherin complexes mediate cell-cell adhesion and are crucial for embryonic
development. Besides their structural function, cadherin complexes also transduce
tension across the junction-actomyosin axis into proportional biochemical
responses. Central to this mechanotransduction is the stretching of the cadherin
F-actin-linker alpha-catenin, which opens its central domain for binding to
effectors such as vinculin. Mechanical unfolding of alpha-catenin leads to force
dependent reinforcement of cadherin-based junctions as studied in cell culture.
The importance of cadherin mechanotransduction for embryonic development has not
been studied yet. Here we used TALEN-mediated gene disruption to perturb
endogenous alphaE-catenin in zebrafish development. Zygotic alpha-catenin mutants
fail to maintain their epithelial barrier, resulting in tissue rupturing. We then
specifically disrupted mechanotransduction, while maintaining cadherin adhesion,
by expressing an alphaE-catenin construct in which the mechanosensitive domain
was perturbed. Expression of either wild-type or mechano-defective alpha-catenin
fully rescues barrier function in alpha-catenin mutants; however, expression of
mechano-defective alpha-catenin also induces convergence and extension defects.
Specifically, the polarization of cadherin-dependent, lamellipodia-driven cell
migration of the lateral mesoderm was lost. These results indicate that cadherin
mechanotransduction is crucial for proper zebrafish morphogenesis, and uncover
one of the essential processes affected by its perturbation.
PMID- 27612509
TI - Energy metabolic state in hypothermically stored boar spermatozoa using a revised
protocol for efficient ATP extraction.
AB - Mammalian spermatozoa utilize ATP as the energy source for key functions on the
route to fertilization. ATP and its precursor nucleotides ADP and AMP are
regularly investigated in sperm physiology studies, mostly by bioluminescence
assays. Assay results vary widely, mainly due to different efficiencies in
nucleotide extraction and prevention of their enzymatic degradation. Here, we
describe a revised, validated protocol for efficient phosphatase inhibition and
adenine nucleotide extraction resulting in consistently high ATP concentrations
exceeding previously reported values for boar spermatozoa up to 20-fold. The
revised assay is applicable for determining ATP concentrations and adenylate
energy charge in extracts from fresh and frozen samples, thereby allowing
simultaneous assessment of semen samples from long-term storage experiments.
After validation, the assay was applied to liquid-preserved boar spermatozoa
stored at 17 degrees C and 5 degrees C for 24 and 72 h. Cooling to 5 degrees C,
but not storage duration, reduced ATP concentration in spermatozoa (P<0.05),
which was accompanied by the appearance of AMP and ADP in the preservation
medium. ATP and energy charge were highly correlated to the proportion of
membrane-intact spermatozoa, supporting the idea of nucleotides leaking through
disrupted membranes in cold-shocked cells. The present assay allows highly
standardized studies of energy metabolism in spermatozoa.
PMID- 27612510
TI - Dining dichotomy: aquatic and terrestrial prey capture behavior in the Himalayan
newt Tylototriton verrucosus.
AB - Transitions between aquatic and terrestrial prey capture are challenging. Trophic
shifts demand a high degree of behavioral flexibility to account for different
physical circumstances between water and air to keep performance in both
environments. The Himalayan newt, Tylototriton verrucosus, is mostly terrestrial
but becomes aquatic during its short breeding period. Nonetheless, it was assumed
that it lacks the capability of trophic behavioral flexibility, only captures
prey on land by its tongue (lingual prehension) and does not feed in water. This
theory was challenged from stomach content analyses in wild populations that
found a variety of aquatic invertebrates in the newts' stomachs during their
breeding season. Accordingly, we hypothesized that T. verrucosus actively changes
its terrestrial prey capture mechanism to hunt for aquatic prey at least during
its aquatic stage. In fact, the kinematic analyses showed that T. verrucosus uses
lingual prehension to capture prey on land but changes to suction feeding for
aquatic strikes. The statistical analyses revealed that terrestrial and aquatic
strikes differ significantly in most kinematic parameters while behavioral
variability does not differ between both behaviors. In turn, the movement
patterns in suction feeding showed a higher degree of coordination between jaw
and hyoid movements compared to the putative primary feeding mode, namely lingual
prehension. We conclude that T. verrucosus, though relatively slow compared to
trophic specialists, benefits from a high degree of behavioral flexibility that
allows exploiting food sources efficiently from two very different habitats.
PMID- 27612511
TI - Excess Poltheta functions in response to replicative stress in homologous
recombination-proficient cancer cells.
AB - DNA polymerase theta (Poltheta) is a specialized A-family DNA polymerase that
functions in processes such as translesion synthesis (TLS), DNA double-strand
break repair and DNA replication timing. Overexpression of POLQ, the gene
encoding Poltheta, is a prognostic marker for an adverse outcome in a wide range
of human cancers. While increased Poltheta dosage was recently suggested to
promote survival of homologous recombination (HR)-deficient cancer cells, it
remains unclear whether POLQ overexpression could be also beneficial to HR
proficient cancer cells. By performing a short interfering (si)RNA screen in
which genes encoding druggable proteins were knocked down in Poltheta
overexpressing cells as a means to uncover genetic vulnerabilities associated
with POLQ overexpression, we could not identify genes that were essential for
viability in Poltheta-overexpressing cells in normal growth conditions. We also
showed that, upon external DNA replication stress, Poltheta expression promotes
cell survival and limits genetic instability. Finally, we report that POLQ
expression correlates with the expression of a set of HR genes in breast, lung
and colorectal cancers. Collectively, our data suggest that Poltheta
upregulation, besides its importance for survival of HR-deficient cancer cells,
may be crucial also for HR-proficient cells to better tolerate DNA replication
stress, as part of a global gene deregulation response, including HR genes.
PMID- 27612512
TI - Mytilus galloprovincialis as a smart micro-pump.
AB - Hydrodynamic performance of the marine mussel, Mytilus galloprovincialis, is
studied with time-resolved particle image velocimetry. We evaluated inhalant
flow, exhalant jet flow, suction performance and flow control capabilities of the
mussels quantitatively. Inhalant flow structures of mussels are measured at the
coronal plane for the first time in literature. Nutrient fluid is convected into
the mussel by three-dimensional sink flow. Inhalant velocity reaches its highest
magnitude inside the mussel mantle while it is accelerating outward from the
mussels. We calculated pressure gradient at the coronal plane. As inhalant flow
approaches the mussel shell tip, suction force generated by the inhalant flow
increases and becomes significant at the shell tip. Likewise, exhalant jet flow
regimes were studied for 17 mussels. Mussels can control their exhalant jet flow
structure from a single potential core region to double potential core region or
vice versa. Peak exhalant jet velocity generated by the mussels changes between
2.77 cm s-1 and 11.1 cm s-1 as a function of mussel cavity volume. Measurements
of hydrodynamic dissipation at the sagittal plane revealed no interaction between
the inhalant and exhalant jet flow, indicating energy-efficient synchronized
pumping mechanism. This efficient pumping mechanism is associated with the flow
turning angle between inhalant and exhalant jet flows, ~90 degrees (s.d. 12
degrees ).
PMID- 27612513
TI - Skeletal muscle growth dynamics and the influence of first-feeding diet in
Atlantic cod larvae (Gadus morhua L.).
AB - Dynamics between hypertrophy (increase in cell size) and hyperplasia (increase in
cell numbers) of white and red muscle in relation to body size [standard length
(SL)], and the influence of the first-feeding diets on muscle growth were
investigated in Atlantic cod larvae (Gadus morhua). Cod larvae were fed copepod
nauplii or rotifers of different nutritional qualities from 4 to 29 days post
hatching (dph), Artemia nauplii from 20 to 40 dph and a formulated diet from 36
to 60 dph. The short period of feeding with cultivated copepod nauplii had a
positive effect on both muscle hyperplasia and hypertrophy after the
copepod/rotifer phase (19 dph), and a positive long term effect on muscle
hypertrophy (60 dph). The different nutritional qualities of rotifers did not
significantly affect muscle growth. We suggest here a model of the dynamics
between hyperplasia and hypertrophy of red and white muscle fibre cells in
relation to cod SL (4 to 30 mm), where the different red and white muscle growth
phases clearly coincided with different metamorphosis stages in cod larvae. These
shifts could be included as biomarkers for the different stages of development
during metamorphosis. The main dietary muscle effect was that hypertrophic growth
of red muscle fibres was stronger in cod larvae that were fed copepods than in
larvae that were fed rotifers, both in relation to larval age and size. Red
muscle fibres are directly involved in larval locomotory performance, but may
also play an important role in the larval myogenesis. This can have a long term
effect on growth potential and fish performance.
PMID- 27612520
TI - Bromate Reduction by Rhodococcus sp. Br-6 in the Presence of Multiple Redox
Mediators.
AB - A bromate (BrO3-)-reducing bacterium, designated Rhodococcus sp. strain Br-6, was
isolated from soil. The strain reduced 250 MUM bromate completely within 4 days
under growth conditions transitioning from aerobic to anaerobic conditions, while
no reduction was observed under aerobic and anaerobic growth conditions. Bromate
was reduced to bromide (Br-) stoichiometrically, and acetate was required as an
electron donor. Interestingly, bromate reduction by strain Br-6 was significantly
dependent on both ferric iron and a redox dye 2,6-dichloroindophenol (DCIP). Cell
free extract of strain Br-6 showed a dicumarol-sensitive diaphorase activity,
which catalyzes the reduction of DCIP in the presence of NADH. Following abiotic
experiments showed that the reduced form of DCIP was reoxidized by ferric iron,
and that the resulting ferrous iron reduced bromate abiotically. Furthermore,
activity staining of the cell free extract revealed that one of diaphorase
isoforms possessed a bromate-reducing activity. Our results demonstrate that
strain Br-6 utilizes multiple redox mediators, that is, DCIP and ferric iron, for
bromate reduction. Since the apparent rate of bromate reduction by this strain
(60 MUM day-1) was 3 orders of magnitude higher than that of known bromate
reducing bacteria, it could be applicable to removal of this probable human
carcinogen from drinking water.
PMID- 27612521
TI - Exploratory Bifactor Analysis: The Schmid-Leiman Orthogonalization and Jennrich
Bentler Analytic Rotations.
AB - Analytic bifactor rotations have been recently developed and made generally
available, but they are not well understood. The Jennrich-Bentler analytic
bifactor rotations (bi-quartimin and bi-geomin) are an alternative to, and
arguably an improvement upon, the less technically sophisticated Schmid-Leiman
orthogonalization. We review the technical details that underlie the Schmid
Leiman and Jennrich-Bentler bifactor rotations, using simulated data structures
to illustrate important features and limitations. For the Schmid-Leiman, we
review the problem of inaccurate parameter estimates caused by the linear
dependencies, sometimes called "proportionality constraints," that are required
to expand a p correlated factors solution into a (p + 1) (bi)factor space. We
also review the complexities involved when the data depart from perfect cluster
structure (e.g., item cross-loading on group factors). For the Jennrich-Bentler
rotations, we describe problems in parameter estimation caused by departures from
perfect cluster structure. In addition, we illustrate the related problems of (a)
solutions that are not invariant under different starting values (i.e., local
minima problems) and (b) group factors collapsing onto the general factor.
Recommendations are made for substantive researchers including examining all
local minima and applying multiple exploratory techniques in an effort to
identify an accurate model.
PMID- 27612522
TI - Induction of labour for postdates in nulliparous women with uncomplicated
pregnancy - is the caesarean section rate really lower?
AB - Induction for "post-dates" is a very common procedure and in Queensland,
Australia, accounts for 35.5% of all inductions. Systematic reviews all conclude
that induction of labour does not increase the risk of caesarean section (CS).
However, these reviews have generally included a mixed population and have not
stratified for parity. We report in a retrospective cohort study involving only
nulliparous women with uncomplicated singleton pregnancy at 40 degrees to 416
weeks that compared to spontaneous labour, incidence of CS was significantly
higher in the induction group, 22.2% versus 12.1% (OR 2.06; 95% CI 1.93-2.20) at
40 degrees to 416 weeks versus spontaneous labour at 40 degrees to 416 weeks;
and also higher at 21.0% versus 14.9% (OR 1.52; 95% CI 1.34-1.73) at 40 degrees
to 406 weeks versus spontaneous labour at 41 degrees to 416 weeks (expectant
management).
PMID- 27612523
TI - Reversal of Aged Muscle Stem Cell Dysfunction.
AB - The loss of muscle stem cell (MuSC) numbers and function in the elderly results
in a dramatic delay or incomplete repair of muscle following injury or surgery.
Prolonged immobility can exacerbate the loss of muscle mass with increased
morbidity of affected patients. Stem cells and their niche cooperate to regulate
the activation, self-renewal, differentiation, and return to quiescence of MuSCs.
Extracellular matrix fibronectin (FN) and MuSC beta1-integrin have been
identified as critical factors in the dysfunction of aging muscle. Reduced
amounts and/or function of beta1-integrin and fibronectin are critical factors in
the decline in MuSC regeneration and homeostasis with aging. Replacement of
fibronectin and/or stimulation of beta1-integrin may provide a novel means to
augment the decline in MuSC function with age.
PMID- 27612524
TI - Detection of Inulin, a Prebiotic Polysaccharide, in Maple Syrup.
AB - Maple syrup is a widely consumed plant-derived natural sweetener produced by
concentrating xylem sap collected from certain maple (Acer) species. During
thermal evaporation of water, natural phytochemical components are concentrated
in maple syrup. The polymeric components from maple syrup were isolated by
ethanol precipitation, dialysis, and anion exchange chromatography and
structurally characterized by glycosyl composition analysis, glycosyl linkage
analysis, and nuclear magnetic resonance spectroscopy. Among the maple syrup
polysaccharides, one neutral polysaccharide was characterized as inulin with a
broad molecular weight distribution, representing the first isolation of this
prebiotic carbohydrate from a xylem sap. In addition, two acidic polysaccharides
with structural similarity were identified as arabinogalactans derived from
rhamnogalacturonan type I pectic polysaccharides.
PMID- 27612525
TI - Prevention of trismus with different pharmacological therapies after surgical
extraction of impacted mandibular third molar.
AB - Aim To assess prevention and reduction of trismus after surgically extracted
impacted mandibular third molars with individual and combined therapy with
corticosteroids and anti-inflammatory analgesics. Methods The research included
60 randomly selected patients (3 groups) attended to the Dental Oral Surgery of
the Public Institution Healthcare Center Zenica during the period January
December 2008. Patients of both genders, 18-45 years of age, were presented
without pain and other inflammatory symptoms at the time of surgery. According to
a scheme established in the research protocol, two medications were administered
orally: methylprednisolone(corticosteroid) 32 mg and meloxicam (non-steroidal
anti-inflammatory analgesic, NSAID) 15 mg as a single drug, or a combination of
both drugs. The level of trismus is assessed on the basis of differences of
preoperative and postoperative values of interincisal spaces when fully opening
the mouth on the second and the seventh post-operative day. The differences
between groups of patients were evaluated by means of Tukey's HSD test. Results
On the second and on the seventh post-operative day significantly better results
were registered in the group that received only corticosteroids and in the group
that received both, corticosteroids and NSAIDs compared to the group that
received only NSAIDs. A tendency of trismus reduction was present in all patient
groups for the second and seventh day after surgery. Conclusion Prevention and
control of postoperative trismus after surgical extraction of impacted mandibular
third molars with combined therapy is effective and superior comparing to
individual therapy with meloxicam-or methylprednisolone alone.
PMID- 27612526
TI - Hemodynamic assessment of hydrops foetalis secondary to transient
myeloproliferative disorder associated with foetal Down syndrome: A case report
and literature review.
PMID- 27612528
TI - Cardiac chondromyxoma.
PMID- 27612529
TI - Congenital left ventricular apical aneurysm presenting as ventricular
tachycardia.
AB - The authors present the case of a 34-year-old male patient seen in our department
due to palpitations. On the electrocardiogram monomorphic ventricular tachycardia
(VT) was documented, treated successfully with amiodarone. The subsequent study
revealed a normal echocardiogram and an apical aneurysm of the left ventricle on
magnetic resonance imaging, confirmed by computed tomography coronary angiography
that also excluded coronary disease. He underwent an electrophysiological study
to determine the origin of the VT and to perform catheter ablation using
electroanatomical mapping. VT was induced and radiofrequency applications were
performed in the left ventricular aneurysm area. VT was no longer inducible, with
acute success. Despite this it was decided to implant a subcutaneous implantable
cardioverter-defibrillator (ICD). Eight months after the ablation the patient was
admitted again due to VT, treated by the ICD.
PMID- 27612530
TI - The Bakri tamponade balloon as an adjunct treatment for refractory postpartum
hemorrhage.
AB - OBJECTIVE: To evaluate the Bakri tamponade balloon as an adjunct treatment for
refractory postpartum hemorrhage (PPH). METHODS: A prospective observational
intervention study was conducted between January 1, 2013, and May 31, 2015, at
Great Lakes Hospital and Moi Teaching and Referral Hospital in Kenya. Eligible
participants were diagnosed with PPH (blood loss >500mL after vaginal or >1000mL
after cesarean delivery, and/or hemodynamic changes suggestive of excessive blood
loss) unresponsive to standard intervention and were treated using the Bakri
balloon. Case report forms were completed for all participants. The primary
endpoint was the frequency of surgery after use of the Bakri balloon. RESULTS:
Among 58 patients, postpartum bleeding was controlled without further surgical
intervention in 55 (95%). Among the 55 women with uterine atony, the Bakri
balloon successful controlled PPH in 52 (95%). Two of the three hysterectomies
performed were for continued bleeding after placement of the Bakri tamponade
balloon. Four maternal deaths occurred. CONCLUSION: The Bakri tamponade balloon
proved an effective adjunct in the management of refractory PPH.
PMID- 27612531
TI - Prevalence of gestational diabetes mellitus according to IADPSG and NICE
criteria.
AB - OBJECTIVE: To investigate the impact of the International Association of Diabetic
Pregnancy Study Group (IADPSG) diagnostic criteria on the prevalence of
gestational diabetes mellitus (GDM) and overt diabetes as compared with the UK
National Institute for Health and Care Excellence (NICE) criteria, and to
evaluate the prevalence of maternal and perinatal outcomes among pregnant women
with fasting plasma glucose (FPG) levels of 5.1-5.5 mmol/L. METHODS: A
retrospective study was undertaken of data for women who underwent a 2-hour 75-g
oral glucose tolerance test at 24-32 weeks of a singleton pregnancy at a center
in Croatia between January 2012 and December 2014. RESULTS: Among 4646 included
women, 1074 (23.1%) had GDM according to IADPSG criteria, 826 (17.8%) would be
diagnosed according to NICE criteria, and 50 (1.1%) had overt diabetes. FPG
levels were 5.1-5.5 mmol/L for 409 (8.8%) women. Compared with a control group
(n=3391), these women had higher odds of large-for-gestational-age newborns (odds
ratio 3.7, 95% CI 2.0-4.6) and cesarean delivery (odds ratio 1.8, 95% CI 1.3
2.3). CONCLUSION: Women with FPG levels of 5.1-5.5 mmol/L have an increased risk
of adverse maternal and perinatal outcome, although they would not be diagnosed
with GDM according to NICE criteria.
PMID- 27612532
TI - Helicobacter pylori infection and pre-eclampsia in a Romanian study group.
PMID- 27612534
TI - Correction: Out-of-hours antibiotic prescription after screening with C reactive
protein: a randomised controlled study.
PMID- 27612533
TI - New clinical decision rule to exclude subarachnoid haemorrhage for acute
headache: a prospective multicentre observational study.
AB - OBJECTIVE: To ensure good outcomes in the management of subarachnoid haemorrhage
(SAH), accurate prediction is crucial for initial assessment of patients
presenting with acute headache. We conducted this study to develop a new clinical
decision rule using only objectively measurable predictors to exclude SAH,
offering higher specificity than the previous Ottawa SAH Rule while maintaining
comparable sensitivity. DESIGN: Multicentre prospective cohort study. SETTING:
Tertiary-care emergency departments of five general hospitals in Japan from April
2011 to March 2014. PARTICIPANTS: Eligible patients comprised 1781 patients aged
>15 years with acute headache, excluding trauma or toxic causes and patients who
presented in an unconscious state. MAIN OUTCOME MEASURES: Definitive diagnosis of
SAH was based on confirmation of SAH on head CT or lumbar puncture findings of
non-traumatic red blood cells or xanthochromia. RESULTS: A total of 1561 patients
were enrolled in this study, of whom 277 showed SAH. Using these enrolled
patients, we reached a rule with mainly categorical predictors used in previous
reports, called the 'Ottawa-like rule', offering 100% sensitivity when using any
of age >=40 years, neck pain or stiffness, altered level of consciousness or
onset during exertion. Using the 1317 patients from whom blood samples were
obtained, a new rule using any of systolic blood pressure >150 mm Hg, diastolic
blood pressure >90 mm Hg, blood sugar >115 mg/dL or serum potassium <3.9 mEq/L
offered 100% sensitivity (95% CI 98.6% to 100%) and 14.5% specificity (12.5% to
16.9%), while the Ottawa-like rule showed the same sensitivity with a lower
specificity of 8.8% (7.2% to 10.7%). CONCLUSIONS: While maintaining equal
sensitivity, our new rule seemed to offer higher specificity than the previous
rules proposed by the Ottawa group. Despite the need for blood sampling, this
method can reduce unnecessary head CT in patients with acute headache. TRIAL
REGISTRATION NUMBER: UMIN 00004871.
PMID- 27612535
TI - Correction: Association of volunteering with mental well-being: a lifecourse
analysis of a national population-based longitudinal study in the UK.
PMID- 27612527
TI - Cannabis and development of dual diagnoses: A literature review.
AB - BACKGROUND: The use of cannabis has garnered more attention recently with ongoing
efforts at marijuana legalization. The consequences of cannabis use are not
clearly understood and remain a concern. OBJECTIVES: To review the acute and
persistent effects of cannabis use and associations with psychiatric disorders.
METHODS: Using Pubmed and PsychInfo, we conducted a narrative review of the
literature on cannabis and psychiatric comorbidity using the keywords cannab*,
marijuana, schizo*, psychosis, mood, depression, mania, bipolar, and anxiety.
RESULTS: There is substantial evidence of cannabis use leading to other illicit
drug use and of an association between cannabis use and psychosis. A few reports
suggest an association with bipolar disorder while the association with
depression and anxiety disorders is mixed. CONCLUSIONS: Whenever an association
is observed between cannabis use and psychiatric disorders, the relationship is
generally an adverse one. Age at the time of cannabis use appears to be an
important factor with stronger associations observed between adolescent onset
cannabis use and later onset of psychiatric disorders. Additional studies taking
into account potential confounds (such as withdrawal symptoms, periods of
abstinence, and other substance use) and moderators (such as age of initiation of
cannabis use, the amount and frequency of drug use, prior history of childhood
maltreatment, and gender) are needed to better understand the psychiatric
consequences of cannabis use.
PMID- 27612537
TI - Correction: Costs associated with functional gastrointestinal disorders and
related signs and symptoms in infants: a systematic review protocol.
PMID- 27612536
TI - Relationship between mobility, violence and major depression among female sex
workers: a cross-sectional study in southern India.
AB - BACKGROUND: The relationship between mobility, violence and mental health has
largely been unexplored in developing countries. This study screens for signs of
major depression, and assesses its association with mobility and violence among
female sex workers (FSWs) in southern India. METHODS: Data (N=2400) for this
study were used from a cross-sectional Behavioral Tracking Survey (BTS-2014)
conducted among FSWs from a southern state of India as part of the Avahan
programme. Major depression of FSWs was assessed using the Patient Health
Questionnaire-2 depression scale. Descriptive statistics, frequency, bivariate,
interaction effect and multivariate logistic regression techniques were used for
the analysis. RESULTS: More than one-fourth of FSWs (29%) screened positive for
major depression. The likelihood of screening positive for major depression was 6
times higher among FSWs who were both mobile for sex work outside their district
of residence and had experienced any violence (combined association) during the
past 1 year (62% vs 19%, adjusted OR 6.1, 95% CI 4.4 to 8.6) compared with those
who reported neither. The individual association results show that FSWs who
reported being mobile outside the district, and FSWs who were beaten or raped in
the past 1 year, were 3 times more likely to screen positive for major
depression. CONCLUSIONS: The findings indicate that violence and mobility are
independently associated with major depression among FSWs. The combined
association of mobility and violence poses a greater risk to the mental health of
FSWs than their independent association. These results point to the need for
creating an enabling environment for FSWs to enhance existing efforts to reduce
the spread of HIV and mental health problems. The study highlights that HIV
prevention efforts among FSWs in India require evidence-based research and
integrated programme approaches to address mental health issues.
PMID- 27612538
TI - Correction: Hundred top-cited articles focusing on acute kidney injury: a
bibliometric analysis.
PMID- 27612541
TI - Correction: Association between hyperglycaemic crisis and long-term major adverse
cardiovascular events: a nationwide population-based, propensity score-matched,
cohort study.
PMID- 27612540
TI - Patients' experiences of a multidisciplinary team-led community case management
programme: a qualitative study.
AB - OBJECTIVES: To explore the views and experiences of patients on the care they
have received while enrolled on the Northumberland High Risk Patient Programme
(NHRPP). This programme involved case finding of frail patients using a
multidisciplinary team (MDT)-led community case management programme, and support
of patients through care planning and regular reviews using primary, community,
secondary and social care professionals. DESIGN: A qualitative study using
semistructured interviews, which were digitally recorded, transcribed and subject
to thematic analysis. SETTING: Community patients receiving primary care in the
county of Northumberland, England. PARTICIPANTS: 23 participants took part, of
which 16 were patients enrolled on the NHRPP, and 7 carers. GP practices were
selected purposively by size, deprivation and location, and patients identified
and invited by General Practitioners to participate. RESULTS: 4 main themes
emerged from the data: awareness and understanding of the NHRPP, confidence in
the primary healthcare team, limitations of home care and the active role of
being a patient. Despite having a low level of awareness of the details of the
NHRPP, participants did think that its broad aim made sense. Participants
discussed their high level of satisfaction with their care and access to team
members. However, some limitations of alternatives to hospital care were
identified, including the need to consider psychological as well as medical
needs, the importance of overnight care and the needs of those without informal
carers. Finally, participants discussed the active nature of being a patient
under the NHRPP if they were to contribute fully to planning and managing their
own care. CONCLUSIONS: This study has identified that a programme of MDT-led case
management was generally very well received by patients and their families.
However, a number of factors were identified that could improve the
implementation of the programme and further research needs to be undertaken to
address these.
PMID- 27612539
TI - Measurement of the severity of disability in community-dwelling adults and older
adults: interval-level measures for accurate comparisons in large survey data
sets.
AB - OBJECTIVES: To (1) create a single metric of disability using Rasch modelling to
be used for comparing disability severity levels across groups and countries, (2)
test whether the interval-level measures were invariant across countries,
sociodemographic and health variables and (3) examine the gains in precision
using interval-level measures relative to ordinal scores when discriminating
between groups known to differ in disability. DESIGN: Cross-sectional, population
based study. SETTING/PARTICIPANTS: Data were drawn from the Survey of Health,
Ageing and Retirement in Europe (SHARE), including comparable data across 16
countries and involving 58 489 community-dwelling adults aged 50+. MAIN OUTCOME
MEASURES: A single metric of disability composed of self-care and instrumental
activities of daily living (IADLs) and functional limitations. We examined the
construct validity through the fit to the Rasch model and the know-groups method.
Reliability was examined using person separation reliability. RESULTS: The single
metric fulfilled the requirements of a strong hierarchical scale; was able to
separate persons with different levels of disability; demonstrated invariance of
the item hierarchy across countries; and was unbiased by age, gender and
different health conditions. However, we found a blurred hierarchy of ADL and
IADL tasks. Rasch-based measures yielded gains in relative precision (11-116%) in
discriminating between groups with different medical conditions. CONCLUSIONS:
Equal-interval measures, with person-invariance and item-invariance properties,
provide epidemiologists and researchers with the opportunity to gain better
insight into the hierarchical structure of functional disability, and yield more
reliable and accurate estimates of disability across groups and countries.
Interval-level measures of disability allow parametric statistical analysis to
confidently examine the relationship between disability and continuous measures
so frequent in health sciences (eg, cholesterol, blood pressure, C reactive
protein).
PMID- 27612542
TI - Trustworthy patient decision aids: a qualitative analysis addressing the risk of
competing interests.
AB - OBJECTIVE: Our aim in this study was to examine the competing interest policies
and procedures of organisations who develop and maintain patient decision aids.
DESIGN: Descriptive and thematic analysis of data collected from a cross
sectional survey of patient decision aid developer's competing interest policies
and disclosure forms. RESULTS: We contacted 25 organisations likely to meet the
inclusion criteria. 12 eligible organisations provided data. 11 organisations did
not reply and 2 declined to participate. Most patient decision aid developers
recognise the need to consider the issue of competing interests. Assessment
processes vary widely and, for the most part, are insufficiently robust to
minimise the risk of competing interests. Only half of the 12 organisations had
competing interest policies. Some considered disclosure to be sufficient, while
others imposed differing levels of exclusion. CONCLUSIONS: Patient decision aid
developers do not have a consistent approach to managing competing interests.
Some have developed policies and procedures, while others pay no attention to the
issue. As is the case for clinical practice guidelines, increasing attention will
need to be given to how the competing interests of contributors of evidence-based
publications may influence materials, especially if they are designed for patient
use.
PMID- 27612544
TI - Novel selective glucocorticoid receptor agonists (SEGRAs) with a covalent warhead
for long-lasting inhibition.
AB - The synthesis and in vitro properties of six analogues of the selective
glucocorticoid receptor (GR) agonist GSK866, bearing a warhead for covalent
linkage to the glucocorticoid receptor, is described.
PMID- 27612543
TI - Citrinovirin with a new norditerpene skeleton from the marine algicolous fungus
Trichoderma citrinoviride.
AB - Citrinovirin (1), a novel norditerpene with an unprecedented carbon skeleton
along with three known compounds, cyclonerodiol (2), 3-(2-hydroxypropyl)-4-(hexa
2E,4E-dien-6-yl)furan-2(5H)-one (3), and 5-hydroxy-3-hydroxymethyl-2-methyl-7
methoxychromone (4), was isolated from the culture of a marine brown alga
endophytic strain (cf-27) of Trichoderma citrinoviride. The structure and
relative configuration of 1 were identified by spectroscopic methods, including
1D/2D NMR and MS. Its absolute configuration was established by analysis of ECD
spectrum, aided by quantum chemical calculations. A plausible biogenetic pathway
is proposed for 1, and it was evaluated to be active against Staphylococcus
aureus.
PMID- 27612545
TI - Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa
inhibitors.
AB - Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as
promising compounds for treating thrombotic disease. In this contribution, we
describe multifaceted exploratory SAR studies of S1'-binding moieties within a
macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the
course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1'
substituent emerged as an improved alternative, offering increased metabolic
stability and lower clearance, while maintaining excellent potency and
selectivity.
PMID- 27612546
TI - Design and synthesis of fluorescent glycolipid photoaffinity probes and their
photoreactivity.
AB - Glycolipid-protein interactions at the cell surface are implicated in various
biological processes. Toward the investigation of glycolipid binding proteins, we
designed and synthesized trifunctional photoaffinity probes, which present a
sugar head group with a triazole linkage to the lipid tail unit containing a
photoreactive group and a fluorescent tag. The glycolipid photoaffinity probes
bearing benzophenone group or diazirine group were evaluated for their
photocrosslinking reactivity toward a carbohydrate head group specific protein.
The diazirine based glycolipid photoaffinity probe was found to be more effective
than the benzophenone-based probe in a comparative analysis involving a
competitive ligand to distinguish a specific binding protein.
PMID- 27612547
TI - Primary cilia are present on human blood and bone marrow cells and mediate
Hedgehog signaling.
AB - Primary cilia are nonmotile, microtubule-based organelles that are present on the
cellular membrane of all eukaryotic cells. Functional cilia are required for the
response to developmental signaling pathways such as Hedgehog (Hh) and Wnt/beta
catenin. Although the Hh pathway has been shown to be active in leukemia and
other blood cancers, there have been no reports describing the presence of
primary cilia in human blood or leukemia cells. In the present study, we show
that nearly all human blood and bone marrow cells have primary cilia (97-99%). In
contrast, primary cilia on AML cell lines (KG1, KG1a, and K562) were less
frequent (10-36% of cells) and were often shorter and dysmorphic, with less well
defined basal bodies. Finally, we show that treatment of blood cells with the Hh
pathway ligand Sonic Hedgehog (SHh) causes translocation of Smoothened (SMO) to
the primary cilia and activation of Hh target genes, demonstrating that primary
cilia in blood cells are functional and participate in Hh signaling. Loss of
primary cilia on leukemia cells may have important implications for aberrant
pathway activation and response to SMO inhibitors currently in clinical
development.
PMID- 27612548
TI - Is personalised medicine the key to heterogeneity in idiopathic pulmonary
fibrosis?
AB - Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia
of unknown cause, characterised by progressive worsening in lung function and
dyspnoea with an associated prognosis similar to or worse than many cancers. As a
better understanding emerges around the pathogenesis and mechanisms driving
disease pathology, a host of novel agents are being tested both pre-clinically
and clinically. However even with this deeper understanding and positive pre
clinical supportive data, negative trial outcomes are frequently reported,
highlighting the problems faced in treating such a heterogeneous disease with a
varied clinical course. Recently, two therapies that slow disease progression,
nintedanib and pirfenidone, have been approved for the treatment of IPF, yet the
clinical unmet need is still high for IPF patients given their failure to stop
disease progression and their potential side-effect profiles. Efforts are being
made to not only understand the underlying pathways and genetics that might
influence the clinical course of the disease, but also the non-invasive
biomarkers that reflect the activity of specific pathways which in turn may
highlight progressive treatment plans for individual patients. The cumulative
data may be based on the identification of subgroups of patients via biomarker
analysis of ongoing clinical trials, or investigation of cohorts of patients over
time to understand the relative role of these mediators in their disease
progression. Below we review the ongoing quest for novel therapeutic approaches
and highlight, where appropriate attempts have been made to identify patients for
which a specific pathway or mediator may be driving disease progression.
PMID- 27612550
TI - Investigation of endosome and lysosome biology by ultra pH-sensitive nanoprobes.
AB - Endosomes and lysosomes play a critical role in various aspects of cell
physiology such as nutrient sensing, receptor recycling, protein/lipid
catabolism, and cell death. In drug delivery, endosomal release of therapeutic
payloads from nanocarriers is also important in achieving efficient delivery of
drugs to reach their intracellular targets. Recently, we invented a library of
ultra pH-sensitive (UPS) nanoprobes with exquisite fluorescence response to
subtle pH changes. The UPS nanoprobes also displayed strong pH-specific buffer
effect over small molecular bases with broad pH responses (e.g., chloroquine and
NH4Cl). Tunable pH transitions from 7.4 to 4.0 of UPS nanoprobes cover the entire
physiological pH of endocytic organelles (e.g., early and late endosomes) and
lysosomes. These unique physico-chemical properties of UPS nanoprobes allowed a
'detection and perturbation' strategy for the investigation of luminal pH in cell
signaling and metabolism, which introduces a nanotechnology-enabled paradigm for
the biological studies of endosomes and lysosomes.
PMID- 27612552
TI - Editorial Commentary: The holy grail of atrial fibrillation.
PMID- 27612551
TI - Cardiovascular disease in patients with rheumatoid arthritis.
AB - The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis
(RA) is 1.5-2-fold higher than age- and sex-matched individuals from the general
population. This excess risk is attributed to the systemic chronic inflammation
which is a hallmark of RA. Challenges to optimizing CV risk management in RA
include the need for improved methods to predict CV risk, and defining the target
risk factor(s) to reduce CV risk. Lessons learned from RA studies can also inform
CV risk prevention in the general population, where inflammation also has an
important role in the pathogenesis of atherosclerosis.
PMID- 27612549
TI - Anti-arrhythmic strategies for atrial fibrillation: The role of computational
modeling in discovery, development, and optimization.
AB - Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with
increased risk of cerebrovascular stroke, and with several other pathologies,
including heart failure. Current therapies for AF are targeted at reducing risk
of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or
rhythm control). Rate control, typically achieved by atrioventricular nodal
blocking drugs, is often insufficient to alleviate symptoms. Rhythm control
approaches include antiarrhythmic drugs, electrical cardioversion, and ablation
strategies. Here, we offer several examples of how computational modeling can
provide a quantitative framework for integrating multiscale data to: (a) gain
insight into multiscale mechanisms of AF; (b) identify and test pharmacological
and electrical therapy and interventions; and (c) support clinical decisions. We
review how modeling approaches have evolved and contributed to the research
pipeline and preclinical development and discuss future directions and challenges
in the field.
PMID- 27612553
TI - Impact of empagliflozin in patients with diabetes and heart failure.
AB - Heart failure (HF) is a common disease with increased risk for mortality and
morbidity among patients with type 2 diabetes mellitus (T2DM). Optimal glycemic
control in this patient population is challenging as many available therapies can
potentially exacerbate symptoms of HF. Empagliflozin is one in a novel class of
agents, the sodium glucose co-transporter 2 (SGLT2) inhibitors, that lowers blood
glucose by increasing urinary glucose excretion and improves glycemic control and
lowers body weight and blood pressure. In the recent EMPA-REG OUTCOME trial,
empagliflozin was shown to improve cardiovascular outcomes in patients with T2DM
and established cardiovascular risk where it reduced HF hospitalizations and
cardiovascular death, with a consistent benefit among patients both with and
without baseline HF. Here, we review the empagliflozin data on HF outcomes and
discuss potential mechanisms for its benefits in HF with a focus on the
potentially significant impact that empagliflozin may have on the care of
patients with T2DM and HF in the future.
PMID- 27612554
TI - Evaluation of Accessory Lacrimal Gland in Muller's Muscle Conjunctival Resection
Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease.
AB - PURPOSE: The accessory lacrimal glands (ALGs) are an understudied component of
the tear functional unit, even though they are important in the development of
dry eye syndrome (DES). To advance our understanding of aging changes,
regenerative potential, and histologic correlates to human characteristics, we
investigated human ALG tissue from surgical samples to determine the presence or
absence of progenitor cell markers and lacrimal epithelial markers and to
correlate marker expression to relevant patient characteristics. MATERIALS AND
METHODS: ALG tissues obtained from Muller's muscle conjunctival resection (MMCR)
specimens were created using tissue microarrays (TMAs). Immunofluorescence
staining of MMCR sections was performed using primary antibodies specific to cell
protein markers. Cell marker localization in TMAs was then assessed by two
blinded observers using a standardized scoring system. Patient characteristics
including age, race, and status of ocular surface health were then compared
against expression of stem cell markers. RESULTS: Human ALG expressed a number of
epithelial markers, and in particular, histatin-1 was well correlated with the
expression of epithelial markers and was present in most acini. In addition, we
noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG
tissue. There was a decrease in precursor cell marker expression with increasing
age. Finally, we noted that a negative association was present between histatin-1
expression and DES. CONCLUSIONS: Thus, we report for the first time that human
ALG tissues contain precursor marker-positive cells and that this marker
expression may decrease with increasing age. Moreover, histatin-1 expression may
be decreased in DES. Future studies will be performed to use these cell markers
to isolate and culture lacrimal epithelial cells from heterogeneous tissues,
determine the relevance of histatin-1 expression to DES, and isolate candidate
precursor cells from ALG tissue.
PMID- 27612555
TI - Increased Steady-State Memory B Cell Subsets Among High-Risk Participants in an
HIV Vaccine Trial.
AB - The success of an HIV vaccine will require induction of a protective immune
response in the most at-risk populations. The increased incidence of HIV
infection in high-risk populations is assumed to be primarily the result of more
frequent exposure to the virus or a greater inoculum of the virus; however,
underlying variations in immune homeostasis may also contribute to HIV
susceptibility and potentially impact vaccine responses and those required for
protection. As an effective humoral immune response is likely to be a critical
component of a protective HIV vaccine, we evaluated the steady-state phenotypic
profile of peripheral blood B cells by flow cytometry from participants in the
HIV Vaccine Trials Network (HVTN) 203 Phase 2a HIV vaccine trial considered to be
at higher risk and lower risk for HIV acquisition. Overall, high-risk
participants exhibited increased frequency of unswitched IgM memory and activated
switched IgD-CD95+ memory B cells than low-risk participants. Most (93%) of the
high-risk male participants were men who have sex with men who engaged in high
risk sexual behavior. High-risk males had a significantly increased frequency of
CXCR3+ IgD-CD95+ B cells than low-risk males. These results suggest that high
risk populations have altered B cell homeostasis. The increased frequency of
activated and memory B cells may suggest increased immune activation in high-risk
populations, which may contribute to possible differential responses to HIV
vaccine strategies.
PMID- 27612556
TI - Quantifying the effect of body mass index, age, and depression severity on 24-h
activity patterns in persons with a lifetime history of affective disorders.
AB - BACKGROUND: Patients with affective disorders of different ages have been found
to present weight changes and different circadian activity patterns. This study
assessed the effects of age, Body Mass Index (BMI) and depression severity on the
activity-rest cycle in persons with affective disorders using a novel
multifactorial 24-h analysis method. METHODS: Two hundred and thirty-six
participants aged between 14 and 85 years underwent 5 to 22 days of actigraphy
monitoring (mean duration = 14 days). BMI was also recorded and symptom severity
was assessed with the Hamilton Depression Rating Scale (HDRS). Participants were
divided into two groups: healthy controls (n = 68) and participants with a
lifetime diagnosis of affective disorders (n = 168). First, the multiple
regression method was employed to formulate the circadian activity pattern in
term of the factors age, BMI and HDRS. For each group, the functional linear
analysis method was applied to assess the relative effects of the factors.
Finally, Wald-tests were used to assess the contribution of each factor on the
circadian activity pattern. RESULTS: In the affective disorders group, higher BMI
was associated with higher activity levels from 3 am until 5.30 am and with lower
activity levels from 10 am until 10.30 pm. Older age was associated with less
activity across the day, evening, and night - from 11 am until 5.30 am. Higher
HDRS scores were associated with higher activity around 1:30 am. In healthy
controls, the effects of BMI and age on activity patterns were less pronounced
and affected a narrower portion of the 24-h period. CONCLUSION: These findings
suggest that older age and higher BMI are linked to lower daytime activity
levels. Higher BMI and worse symptom severity were also associated with nocturnal
activity patterns suggestive of sleep disturbances. The influence of age and BMI
on 24-h activity profiles appear to be especially pronounced in people with
affective disorders.
PMID- 27612557
TI - Inhibition of Aurora kinases induces apoptosis and autophagy via
AURKB/p70S6K/RPL15 axis in human leukemia cells.
AB - Leukemia is a common malignancy of blood cells with poor prognosis in many
patients. Aurora kinases, a family of serine/threonine kinases, play a key role
in regulating cell division and mitosis and are linked to tumorigenesis,
metastasis, and poor prognosis in many human cancers including leukemia and
lymphoma. Danusertib (Danu) is a pan-inhibitor of Aurora kinases with few data
available in leukemia therapy. This study aimed to identify new molecular targets
for Aurora kinase inhibition in human leukemia cells using quantitative proteomic
analysis followed by verification experiments. There were at least 2932 proteins
responding to Danu treatment, including AURKB, p70S6K, and RPL15, and 603
functional proteins and 245 canonical signaling pathways were involved in
regulating cell proliferation, metabolism, apoptosis, and autophagy. The
proteomic data suggested that Danu-regulated RPL15 signaling might contribute to
the cancer cell killing effect. Our verification experiments confirmed that Danu
negatively regulated AURKB/p70S6K/RPL15 axis with the involvement of
PI3K/Akt/mTOR, AMPK, and p38 MAPK signaling pathways, leading to the induction of
apoptosis and autophagy in human leukemia cells. Further studies are warranted to
verify the feasibility via targeting AURKB/p70S6K/RPL15 axis for leukemia
therapy.
PMID- 27612558
TI - Glutamate release inhibitor, Riluzole, inhibited proliferation of human
hepatocellular carcinoma cells by elevated ROS production.
AB - Liver cancer is one of the common malignancies in many countries and an
increasing cause of cancer death. Despite of that, there are few therapeutic
options available with inconsistent outcome, raising a need for developing
alternative therapeutic options. Through a drug repositioning screening, we
identified and investigated the action mechanism of the Riluzole, an amyotrophic
lateral sclerosis (ALS) drug, on hepatocellular carcinoma (HCC) therapy.
Treatment of the Riluzole leads to a suppression of cell proliferation in liver
primary cancer cells and cancer cell lines. In addition, Riluzole induced caspase
dependent apoptosis and G2/M cell cycle arrest in SNU449 and Huh7 cell lines. In
a line with the known function of glutamate release inhibitor, we found Riluzole
treated cells have increased the level of inner cellular glutamate that in turn
decrease the glutathione (GSH) level and finally augment the reactive oxygen
species (ROS) production. We confirm this finding in vivo by showing the Riluzole
induced GSH and ROS changes in a Huh7 xenograft cancer model. Altogether, these
data suggest the anti-cancer effect of Riluzole on hepatocellular carcinoma and
the suppression of glutamate signaling might be a new target pathway for HCC
therapy.
PMID- 27612560
TI - Income differences in social control of eating behaviors and food choice
priorities among southern rural women in the US: A qualitative study.
AB - The role of social influences on rural women's food choice is not well
understood. Rural adults experience high rates of obesity and poor diet quality
prompting exploration of how social factors influence food choice in this
population. Semi-structured qualitative interviews were conducted with 20 women
in rural North Central Florida. Women were purposively sampled and stratified by
race and income. Lower income was defined as household income at or below 185% of
the federal poverty level (FPL). Women at or below 185% poverty level (BPL)
experienced direct social control of their eating behaviors, which occurred when
social network members explicitly regulated or otherwise sanctioned eating
behaviors or food choices. Women above 185% of the federal poverty level (APL)
internalized social norms and self-regulated their eating behaviors to maintain
healthy habits. APL women described choosing foods for health reasons whereas BPL
women offered a variety of reasons including taste, convenience, family history,
price, health, and routine. Findings suggest that women in different income
groups have different social influences working to help them regulate eating
behaviors as well as diverse priorities influencing their food choices. Future
interventions to promote healthy eating may be more effective by incorporating
social network members and framing intervention messages so they are consistent
with priorities.
PMID- 27612559
TI - Risk factors for eating disorder symptoms at 12 years of age: A 6-year
longitudinal cohort study.
AB - Eating disorders pose risks to health and wellbeing in young adolescents, but
prospective studies of risk factors are scarce and this has impeded prevention
efforts. This longitudinal study aimed to examine risk factors for eating
disorder symptoms in a population-based birth cohort of young adolescents at 12
years. Participants from the Gateshead Millennium Study birth cohort (n = 516;
262 girls and 254 boys) completed self-report questionnaire measures of eating
disorder symptoms and putative risk factors at age 7 years, 9 years and 12 years,
including dietary restraint, depressive symptoms and body dissatisfaction. Body
mass index (BMI) was also measured at each age. Within-time correlates of eating
disorder symptoms at 12 years of age were greater body dissatisfaction for both
sexes and, for girls only, higher depressive symptoms. For both sexes, higher
eating disorder symptoms at 9 years old significantly predicted higher eating
disorder symptoms at 12 years old. Dietary restraint at 7 years old predicted
boys' eating disorder symptoms at age 12, but not girls'. Factors that did not
predict eating disorder symptoms at 12 years of age were BMI (any age), girls'
dietary restraint at 7 years and body dissatisfaction at 7 and 9 years of age for
both sexes. In this population-based study, different patterns of predictors and
correlates of eating disorder symptoms were found for girls and boys. Body
dissatisfaction, a purported risk factor for eating disorder symptoms in young
adolescents, developed concurrently with eating disorder symptoms rather than
preceding them. However, restraint at age 7 and eating disorder symptoms at age 9
years did predict 12-year eating disorder symptoms. Overall, our findings suggest
that efforts to prevent disordered eating might beneficially focus on
preadolescent populations.
PMID- 27612561
TI - Participation in and adherence to physical exercise after completion of primary
cancer treatment.
AB - BACKGROUND: The purpose of this study was to identify demographic, clinical,
psychosocial, physical and environmental factors that are associated with
participation in and adherence to a combined resistance and endurance exercise
program among cancer survivors, shortly after completion of primary cancer
treatment. Data from the randomized controlled Resistance and Endurance exercise
After ChemoTherapy (REACT) study were used for this study. METHODS: The
participants of the REACT study were randomly allocated to either a high
intensity (HI) or low-to-moderate intensity (LMI) exercise program. Patients'
participation rate was defined as the cancer survivors' decision to participate
in the REACT study. Exercise adherence reflected participants' attendance to the
scheduled exercise sessions and their compliance to the prescribed exercises.
High session attendance rates were defined as attending at least 80 % of the
sessions. High compliance rates were defined as performing at least of 90 % of
the prescribed exercise across all sessions. Correlates of exercise adherence
were studied separately for HI and LMI exercise. Demographic, clinical, and
physical factors were assessed using self-reported questionnaires. Relevant
clinical information was extracted from medical records. Multivariable logistic
regression analyses were applied to identify correlates that were significantly
associated with participation, high session attendance, high compliance with
resistance and high compliance with endurance exercises. RESULTS: Participants
were more likely to have higher education, be non-smokers, have lower
psychological distress, higher outcome expectations, and perceive more exercise
barriers than non-participants. In HI exercise, higher self-efficacy was
significantly associated with high session attendance and high compliance with
endurance exercises, and lower psychological distress was significantly
associated with high compliance with resistance exercises. In LMI exercise, being
a non-smoker was significantly associated with high compliance with resistance
exercises and higher BMI was significantly associated with high compliance with
resistance and endurance exercises. Furthermore, breast cancer survivors were
less likely to report high compliance with resistance and endurance exercises in
LMI exercise compared to survivors of other types of cancer. The discriminative
ability of the multivariable models ranged from 0.62 to 0.75. CONCLUSION: Several
demographic, clinical and psychosocial factors were associated with participation
in and adherence to exercise among cancer survivors. Psychosocial factors were
more strongly associated with adherence in HI than LMI exercise. TRIAL
REGISTRATION: This study was registered at the Netherlands Trial Register [
NTR2153 ] on the 5(th) of January 2010.
PMID- 27612562
TI - The Stroke and Carer Optimal Health Program (SCOHP) to enhance psychosocial
health: study protocol for a randomized controlled trial.
AB - BACKGROUND: Stroke is a leading cause of disability and distress, and often
profoundly affects the quality of life of stroke survivors and their carers. With
the support of carers, many stroke survivors are returning to live in the
community despite the presence of disability and ongoing challenges. The sudden
and catastrophic changes caused by stroke affects the mental, emotional and
social health of both stroke survivors and carers. The aim of this study is to
evaluate a Stroke and Carer Optimal Health Program (SCOHP) that adopts a person
centred approach and engages collaborative therapy to educate, support and
improve the psychosocial health of stroke survivors and their carers. METHODS:
This study is a prospective randomised controlled trial. It will include a total
of 168 stroke survivors and carers randomly allocated into an intervention group
(SCOHP) or a control group (usual care). Participants randomised to the
intervention group will receive nine (8 + 1 booster) sessions guided by a
structured workbook. The primary outcome measures for stroke survivors and carers
will be health-related quality of life (AQoL-6D and EQ-5D) and self-efficacy
(GSE). Secondary outcome measures will include: anxiety and depression (HADS);
coping (Brief COPE); work and social adjustment (WSAS); carer strain (MCSI);
carer satisfaction (CASI); and treatment evaluation (TEI-SF and CEQ). Process
evaluation and a health economic cost analysis will also be conducted.
DISCUSSION: We believe that this is an innovative intervention that engages the
stroke survivor and carer and will be significant in improving the psychosocial
health, increasing independence and reducing treatment-related costs in this
vulnerable patient-carer dyad. In addition, we expect that the intervention will
assist carers and stroke survivors to negotiate the complexity of health services
across the trajectory of care and provide practical skills to improve self
management. TRIAL REGISTRATION: ACTRN12615001046594 . Registered on 7 October
2015.
PMID- 27612563
TI - Comparative analysis of housekeeping and tissue-specific driver nodes in human
protein interaction networks.
AB - BACKGROUND: Several recent studies have used the Minimum Dominating Set (MDS)
model to identify driver nodes, which provide the control of the underlying
networks, in protein interaction networks. There may exist multiple MDS
configurations in a given network, thus it is difficult to determine which one
represents the real set of driver nodes. Because these previous studies only
focus on static networks and ignore the contextual information on particular
tissues, their findings could be insufficient or even be misleading. RESULTS: In
this study, we develop a Collective-Influence-corrected Minimum Dominating Set
(CI-MDS) model which takes into account the collective influence of proteins. By
integrating molecular expression profiles and static protein interactions, 16
tissue-specific networks are established as well. We then apply the CI-MDS model
to each tissue-specific network to detect MDS proteins. It generates almost the
same MDSs when it is solved using different optimization algorithms. In addition,
we classify MDS proteins into Tissue-Specific MDS (TS-MDS) proteins and
HouseKeeping MDS (HK-MDS) proteins based on the number of tissues in which they
are expressed and identified as MDS proteins. Notably, we find that TS-MDS
proteins and HK-MDS proteins have significantly different topological and
functional properties. HK-MDS proteins are more central in protein interaction
networks, associated with more functions, evolving more slowly and subjected to a
greater number of post-translational modifications than TS-MDS proteins. Unlike
TS-MDS proteins, HK-MDS proteins significantly correspond to essential genes,
ageing genes, virus-targeted proteins, transcription factors and protein kinases.
Moreover, we find that besides HK-MDS proteins, many TS-MDS proteins are also
linked to disease related genes, suggesting the tissue specificity of human
diseases. Furthermore, functional enrichment analysis reveals that HK-MDS
proteins carry out universally necessary biological processes and TS-MDS proteins
usually involve in tissue-dependent functions. CONCLUSIONS: Our study uncovers
key features of TS-MDS proteins and HK-MDS proteins, and is a step forward
towards a better understanding of the controllability of human interactomes.
PMID- 27612564
TI - Open arthrolysis for elbow stiffness increases carrying angle but has no impact
on functional recovery.
AB - BACKGROUND: With the exception of normal anatomic changes in the medial
collateral ligament and radial head, other factors related to carrying angle
changes have not been systematically studied. We reviewed patients who underwent
open arthrolysis of the elbow, and evaluated if open arthrolysis could change
carrying angle. We then identified factors associated with carrying angle
changes. METHODS: Fifty patients with a minimum of 24 months of follow-up after
open arthrolysis were evaluated retrospectively. Preoperative and postoperative
carrying angles were compared. RESULTS: The carrying angles of 36 elbows in 36
patients were unchanged after surgery (Group A), while the carrying angles of 14
elbows in 14 patients increased postoperatively (Group B). In Group A, mean
postoperative extension and flexion were 7 degrees (range 0-24 degrees ) and 125
degrees (range 10-135 degrees ) respectively, while mean postoperative pronation
and supination were 60 degrees (range 50-80 degrees ) and 65 degrees (range 30
85 degrees ), respectively. In Group B, mean postoperative extension and flexion
were 25 degrees (range 0-40 degrees ) and 128 degrees (range 60-138 degrees ),
while mean postoperative pronation and supination were 65 degrees (range 45-85
degrees ) and 60 degrees (range 45-75 degrees ), respectively. No significant
difference in range of motion and Mayo Elbow Performance Score was observed
between the two groups. CONCLUSIONS: During open arthrolysis, humeral trochlea
debridement and techniques for improving forearm rotation could increase carrying
angle. However, this had no impact on elbow functional recovery.
PMID- 27612565
TI - Human fetal mesenchymal stem cell secretome enhances bone consolidation in
distraction osteogenesis.
AB - BACKGROUND: Distraction osteogenesis (DO) is one of the most dramatic
reconstructive techniques for inducing bone regeneration, but it involves an
undesirably long period for bone consolidation. Developing innovative approaches
to enhance bone consolidation is a burning need. Human fetal mesenchymal stem
cells (hFMSCs) have been shown to express more primitive developmental genes than
those of human adult mesenchymal stem cells (hAMSCs), which is a preferable
source for cell therapy and tissue regeneration. In the present study, we
investigated the immunogenicity of using the human mesenchymal stem cell (MSC)
secretome on rat cells, the effects of secretome on osteogenic differentiation of
rat bone marrow-derived MSCs (rBMSCs), and the potential application of hFMSC
secretome in promoting bone consolidation in a rat DO model. METHODS: Secretome
was collected from MSC culture and was used to treat rBMSCs. Following secretome
treatment, cell proliferation, alkaline phosphatase staining, Alizarin Red S
staining, and mRNA expression of osteogenic differentiation-related genes
(including ALP, Runx2, OCN, OPN, and Osx) in the rBMSCs were checked, as well as
mixed rat peripheral blood lymphocyte reaction. hFMSC secretome was injected
locally into the regenerates from the end of lengthening every 3 days in the rat
DO model, until termination. The regenerates were subject to weekly x-rays, micro
computed tomography (MUCT) and mechanical testing examination. The bone quality
was assessed by histology and immunohistochemistry examinations. RESULTS:
Compared to the secretome from rBMSCs and hAMSCs, hFMSC secretome had the best
osteogenic induction ability and low immunogenicity. hFMSC secretome with
different doses showed no effect on cell viability. hFMSC secretome at the dose
of 100 MUg/MUl could significantly increase the expression of alkaline
phosphatase and all the osteogenic marker genes, as well as the amount of calcium
deposits in the rBMSCs. Finally, the local application of hFMSC secretome in
distraction regenerates in a rat DO model significantly improved bone
consolidation according to the results of MUCT, mechanical test, and histological
and immunohistochemistry analysis. CONCLUSIONS: The current study demonstrated
that hFMSC secretome promotes osteogenesis of rBMSCs and bone consolidation
during DO. hFMSC secretome may be a new therapeutic strategy to enhance bone
consolidation in patients undergoing DO treatment.
PMID- 27612566
TI - Predicting invasive fungal disease due to Candida species in non-neutropenic,
critically ill, adult patients in United Kingdom critical care units.
AB - BACKGROUND: Given the predominance of invasive fungal disease (IFD) amongst the
non-immunocompromised adult critically ill population, the potential benefit of
antifungal prophylaxis and the lack of generalisable tools to identify high risk
patients, the aim of the current study was to describe the epidemiology of IFD in
UK critical care units, and to develop and validate a clinical risk prediction
tool to identify non-neutropenic, critically ill adult patients at high risk of
IFD who would benefit from antifungal prophylaxis. METHODS: Data on risk factors
for, and outcomes from, IFD were collected for consecutive admissions to adult,
general critical care units in the UK participating in the Fungal Infection Risk
Evaluation (FIRE) Study. Three risk prediction models were developed to model the
risk of subsequent Candida IFD based on information available at three time
points: admission to the critical care unit, at the end of 24 h and at the end of
calendar day 3 of the critical care unit stay. The final model at each time point
was evaluated in the three external validation samples. RESULTS: Between July
2009 and April 2011, 60,778 admissions from 96 critical care units were
recruited. In total, 359 admissions (0.6 %) were admitted with, or developed,
Candida IFD (66 % Candida albicans). At the rate of candidaemia of 3.3 per 1000
admissions, blood was the most common Candida IFD infection site. Of the initial
46 potential variables, the final admission model and the 24-h model both
contained seven variables while the end of calendar day 3 model contained five
variables. The end of calendar day 3 model performed the best with a c index of
0.709 in the full validation sample. CONCLUSIONS: Incidence of Candida IFD in UK
critical care units in this study was consistent with reports from other European
epidemiological studies, but lower than that suggested by previous hospital-wide
surveillance in the UK during the 1990s. Risk modeling using classical
statistical methods produced relatively simple risk models, and associated
clinical decision rules, that provided acceptable discrimination for identifying
patients at 'high risk' of Candida IFD. TRIAL REGISTRATION: The FIRE Study was
reviewed and approved by the Bolton NHS Research Ethics Committee (reference:
08/H1009/85), the Scotland A Research Ethics Committee (reference: 09/MRE00/76)
and the National Information Governance Board (approval number: PIAG 2
10(f)/2005).
PMID- 27612568
TI - Biotechnology and the Mine of Tomorrow.
AB - Biotechnology could provide many innovative alternatives for changing the way
metals are obtained. Microbes have been used to dissolve metallic minerals and
release metal ions into solution, from which pure metal can be obtained by
electrolysis. Plants that accumulate metals in their roots and leaves have been
used to concentrate metals, and mineral-binding peptides might be used to
separate minerals. However, for billions of years microbes have been interacting
with metals. Microbial communities in and near mineral sources are therefore a
rich source of genetic information which could be used to create synthetic or
modified microbiomes that concentrate metals. This would be a complete paradigm
change with enormous scope for transforming the way metals are obtained.
PMID- 27612567
TI - Artificial Nose Technology: Status and Prospects in Diagnostics.
AB - Biomimetic crossreactive sensor arrays have been used to detect and analyze a
wide variety of vapor and liquid components in applications such as food science,
public health and safety, and diagnostics. As technology has advanced over the
past three decades, these systems have become selective, sensitive, and
affordable. Currently, the need for noninvasive and accurate devices for early
disease diagnosis remains a challenge. This Opinion article provides an overview
of the various types of biomimetic crossreactive sensor arrays (also referred to
as electronic noses or tongues in the literature), their current use and future
directions, and an outlook for future technological development.
PMID- 27612569
TI - Decreasing incidence of coronary heart disease in extreme obesity (BMI>=40)-A
single centre experience.
AB - AIM: The aim of our comprehensive single centre analysis was to evaluate the
incidence of coronary heart disease (CHD) in extremely obese patients. METHODS
AND RESULTS: Between 2005 and 2015 we investigated retrospectively 23,359
patients undergoing cardiac catheterisation in our institution. Patients were
divided in six weight classes according to World Health Organization (WHO)
criteria [1] (WHO, 2000). Cardiovascular risk factors, comorbidities, CCS stadium
[2] (Cox and Naylor, 1992) and NYHA functional class [3] (The Criteria Committee
of the New York Heart Association, 1994) were retrieved from electronic patient
records. Using multivariable analysis the odds ratio for the target variable CHD
with presence of >50% angiographic stenosis was >=1 with regard to age (OR 1.049,
95% CI 1.045-1.052), male sex (OR 2.507, 95% CI 2.329-2.699), cardiovascular risk
factors, atherosclerosis (OR 1.651, 95% CI 1.498-1.820), and presence of angina
(OR 4.408, 95% CI 3.892-4.993). NYHA functional class I-IV, absence of angina (OR
0.818, 95% CI 0.729-0.918), and BMI>=40 (OR 0.592, 95% CI 0.494-0.709) resulted
in an odds ratio of <=1. Underweight patients had a higher (5.3%) and overweight
(1.2%) and obese patients (class I 0.9% and II 1.1%) a slightly lower all-cause
in-hospital mortality compared to extremely obese patients (1.6%). CONCLUSION:
Severely obese patients treated in our hospital surprisingly showed a decreased
incidence of CHD (46.1% in normal weight and 38.6% in extremely obese patients)
while comorbidities increased CHD as expected. Although CHD burden was lower,
obesity and associated comorbidities resulted in higher all-cause-in-hospital
mortality.
PMID- 27612570
TI - Neutrophil gelatinase-associated lipocalin (NGAL) predicts the occurrence of
malaria-induced acute kidney injury.
AB - BACKGROUND: Acute kidney injury (AKI) is a frequently encountered complication of
imported Plasmodium falciparum infection. Markers of structural kidney damage
have been found to detect AKI earlier than serum creatinine-based prediction
models but have not yet been evaluated in imported malaria. This pilot study aims
to explore the predictive performance of neutrophil gelatinase-associated
lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with
imported P. falciparum infection. METHODS: Thirty-nine patients with imported
falciparum malaria from the Rotterdam Malaria Cohort with available serum and
urine samples at presentation were included. Ten of these patients met the
criteria for severe malaria. The predictive performance of NGAL and KIM-1 as
markers for AKI was compared with that of serum creatinine. RESULTS: Six of the
39 patients (15 %) developed AKI. Serum and urine NGAL and urine KIM-1 were all
found to have large areas under the receiver operating characteristics curves
(AUROC) for predicting AKI. Urine NGAL was found to have an excellent performance
with positive predictive value (PPV) of 1.00 (95 % CI 0.54-1.00), a negative
predictive value (NPV) of 1.00 (95 % CI 0.89-1.00) and an AUROC of 1.00 (95 % CI
1.00-1.00). CONCLUSION: A good diagnostic performance of NGAL and KIM-1 for AKI
was found. Particularly, urine NGAL was found to have an excellent predictive
performance. Larger studies are needed to demonstrate whether these biomarkers
are superior to serum creatinine as predictors for AKI in P. falciparum malaria.
PMID- 27612571
TI - A pilot study among older adults of the concordance between their self-reports to
a health survey and spousal proxy reports on their behalf.
AB - BACKGROUND: Proxy respondents are frequently used in health surveys, and the
proxy is most often the spouse. Longstanding concerns linger, however, about the
validity of using spousal proxies, especially for older adults. The purpose of
this pilot study was to evaluate the concordance between self-reports and spousal
proxy reports to a standard health survey in a small convenience sample of older
married couples. METHODS: We used the Seniors Together in Aging Research (STAR)
volunteer registry at the University of Iowa to identify and consent a cross
sectional, convenience sample of 28 married husband and wife couples. Private,
personal interviews with each member of the married couple using a detailed
health survey based on the 2012 Health and Retirement Study (HRS) instrument were
conducted using computer assisted personal interviewing software. Within couples,
each wife completed the health survey first for herself and then for her husband,
and each husband completed the health survey first for himself and then for his
wife. The health survey topics included health ratings, health conditions,
mobility, instrumental activities of daily living (IADLs), health services use,
and preventative services. Percent of agreement and prevalence and bias adjusted
kappa statistics (PABAKs) were used to evaluate concordance. RESULTS: PABAK
coefficients indicated moderate to excellent concordance (PABAKs >0.60) for most
of the IADL, health condition, hospitalization, surgery, preventative service,
and mobility questions, but only slight to fair concordance (PABAKs = -0.21 to
0.60) for health ratings, and physician and dental visits. CONCLUSIONS: These
results do not allay longstanding concerns about the validity of routinely using
spousal proxies in health surveys to obtain health ratings or the number of
physician and dental visits among older adults. Further research is needed in a
nationally representative sample of older couples in which each wife completes
the health survey first for herself and then for her husband, each husband
completes the health survey first for himself and then for his wife, and both
spouses' Medicare claims are linked to their health survey responses to determine
not just the concordance between spousal reports, but the concordance of those
survey responses to the medical record.
PMID- 27612572
TI - Reasons for current E-cigarette use among U.S. adults.
AB - E-cigarette use has increased rapidly among U.S. adults. However, reasons for use
among adults are unclear. We assessed reasons for e-cigarette use among a
national sample of U.S. adults. Data were collected via online surveys among U.S.
adults aged 18 or older from April through June 2014. Descriptive and
multivariate regression analyses were conducted to assess reasons for e-cigarette
use among 2448 current e-cigarette users, by sociodemographic characteristics and
product type. Assessed reasons included cessation/health, consideration of
others, convenience, cost, curiosity, flavoring, and simulation of conventional
cigarettes. Among current e-cigarette users, 93% were also current cigarette
smokers. The most common reasons for e-cigarette use were cessation/health
(84.5%), consideration of others (71.5%), and convenience (56.7%). The prevalence
of citing convenience (adjusted prevalence ratio [aPR]=1.49) and curiosity
(aPR=1.54) as reasons for e-cigarette use were greater among current cigarette
smokers than nonsmokers (P<0.05). The prevalence of citing flavoring as a reason
for use was greater among adults aged 18 to 24 (aPR=2.02) than 55 or older
(P<0.05). Tank use was associated with greater prevalence of citing every
assessed reason except convenience and curiosity. Cessation- and health-related
factors are primary reasons cited for e-cigarette use among adults, and
flavorings are more commonly cited by younger adults. Efforts are warranted to
provide consumers with accurate information on the health effects of e-cigarettes
and to ensure that flavoring and other unregulated features do not promote
nicotine addiction, particularly among young adults.
PMID- 27612573
TI - Food insecurity and cardiovascular health: Findings from a statewide population
health survey in Wisconsin.
AB - BACKGROUND: The social and economic environment has become a major area of
interest regarding the determinants of cardiovascular health. Among markers of
economic distress, food insecurity has been found associated with metabolic
disorders, dyslipidemia, and obesity, but no previous studies have examined its
association with overall cardiovascular health. METHODS AND RESULTS: We conducted
a cross-sectional analysis among 2935 participants in the Survey of the Health of
Wisconsin (SHOW), a statewide population-based representative sample. The
presence of food insecurity was determined by an affirmative answer to the
question "In the last 12months, have you been concerned about having enough food
for you or your family?" Cardiovascular health (CVH) was defined based on the
American Heart Association Life's Simple 7 criteria and classified as "poor,"
"intermediate," or "ideal" using previously published criteria. "Good" CVH was
defined as having no poor in any of the seven criteria (any amount of
intermediate or ideal). Crude and adjusted odds ratios (OR) of good CVH according
to presence of food insecurity were calculated using logistic regression models.
Overall, food insecurity was associated with a decreased likelihood of good CVH
(OR 0.53; 95% Confidence Interval 0.31 to 0.92; p=0.02). This association
persisted in models controlling for age, gender, race, and urbanization.
CONCLUSIONS: Participants who were food insecure were significantly less likely
to have good CVH compared to participants who were food secure. Even though this
study cannot confirm causality, these results suggest that food insecurity might
be one of several socio-economic barriers contributing to poor CVH.
PMID- 27612574
TI - Effects of physical activity on schoolchildren's academic performance: The Active
Smarter Kids (ASK) cluster-randomized controlled trial.
AB - OBJECTIVE: To investigate the effect of a seven-month, school-based cluster
randomized controlled trial on academic performance in 10-year-old children.
METHODS: In total, 1129 fifth-grade children from 57 elementary schools in Sogn
og Fjordane County, Norway, were cluster-randomized by school either to the
intervention group or to the control group. The children in the 28 intervention
schools participated in a physical activity intervention between November 2014
and June 2015 consisting of three components: 1) 90min/week of physically active
educational lessons mainly carried out in the school playground; 2) 5min/day of
physical activity breaks during classroom lessons; 3) 10min/day physical activity
homework. Academic performance in numeracy, reading and English was measured
using standardized Norwegian national tests. Physical activity was measured
objectively by accelerometry. RESULTS: We found no effect of the intervention on
academic performance in primary analyses (standardized difference 0.01-0.06,
p>0.358). Subgroup analyses, however, revealed a favorable intervention effect
for those who performed the poorest at baseline (lowest tertile) for numeracy
(p=0.005 for the subgroup*group interaction), compared to controls (standardized
difference 0.62, 95% CI 0.19-1.07). CONCLUSIONS: This large, rigorously conducted
cluster RCT in 10-year-old children supports the notion that there is still
inadequate evidence to conclude that increased physical activity in school
enhances academic achievement in all children. Still, combining physical activity
and learning seems a viable model to stimulate learning in those academically
weakest schoolchildren.
PMID- 27612575
TI - The risks of pulmonary embolism and upper gastrointestinal bleeding beyond 35days
after total hip replacement for coxarthrosis among middle-aged patients: A cross
over cohort.
AB - Prophylactic anticoagulation is recommended up to 35days after total hip
replacement (THR). Although several observational studies have assessed the
incidence of thrombotic events or bleeding events after THR, the corresponding
measures of association have never been studied concomitantly. Here, we evaluated
the duration of the elevated risks (relative to the baseline risk) of both venous
thromboembolic events and bleeding events after THR for coxarthrosis among middle
aged patients. This was a population-based, cross-over cohort study of data
extracted from the French national inpatient database between 2007 and 2013. We
included middle-aged patients (aged 45 to 69) having undergone THR for
coxarthrosis. We compared the numbers of pulmonary embolisms (PEs) (respectively
upper gastrointestinal bleedings (UGIBs)) following the THR with the numbers
occurring during three unexposed periods one year later. This enabled us to
estimate the odds ratio (OR) [95% confidence interval (CI)] for each of six
successive 35-day intervals. The study included 108,099 patients. The ORs for PE
were respectively 12.4 (95% CI, 8.6-17.8) (absolute risk difference rate per
100,000 (ARD/100,000)=130) and 5.0 (95% CI, 3.4-7.4) (ARD/100,000=52) for the
first two 35-day intervals, and the risk was close to 1 thereafter. The risk of
UGIB fell quickly, with an OR of 6.5 (95% CI, 4.6-9.1) (ARD/100,000=83) and 0.8
(95% CI, 0.4-1.6) for the first two 35-day intervals, respectively. The majority
of UGIBs occurred during the inpatient stay for THR. Among middle-aged patients,
the risk of a PE remains elevated beyond 35days after THR for coxarthrosis,
whereas the risk of a UGIB remains elevated for the first 35days only.
PMID- 27612576
TI - Dose-response gradients between a composite measure of six risk factors and
cognitive decline and cardiovascular disease.
AB - We created a composite risk factor index which includes 6 risk factors (diabetes,
hypertension, obesity, depression, sedentary lifestyle, and current smoking)
previously shown to be associated with cognitive decline (CD) and Alzheimer's
disease (AD) as well as cardiovascular disease (CVD). Using 2011 Behavioral Risk
Factor Surveillance System results for 95,147 adults ages >=45years we found that
77.3% of study adults reported >=1 risk factor (RF) while <1% reported all 6.
Reporting any RFs increased risk for CD and CVD, with a dose-response gradient
shown for increasing numbers of RFs from 0 to 6. Number of RFs, % of adults with
CD and CVD respectively were: 0 RF: 5.8% w/CD, 4.4% w/CVD; 1 RF: 9.6% w/CD, 10.8%
w/CVD; 2 RF: 12.7% w/CD, 17.6% w/CVD; 3 RF: 19.3% w/CD, 23.7% w/CVD; 4 RF: 24.6%
w/CD, 29.7% w/CVD: 5 RF: 39.0% w/CD. 32.2% w/CVD; and all 6 RF: 54.4% w/CD and
43.7% w/CVD. Adjusted odds ratios (ORs) were similar except they tended to be
higher for CVD compared with CD, with ORs for all 6 RF compared with 0 RF of 11.2
(95% confidence interval 5.2-24.3) for CD and 16.3 (8.5-31.2) for CVD. While dose
response gradients had been reported for individual RFs, our study found dose
response gradients for increasing numbers of RFs and similar strengths of
associations for CD and CVD, plus adds prevalence results from a representative
survey. The similarity between CVD and CD results supports evidence from other
studies and suggests potential benefits of coordinating CVD and CD/AD prevention
efforts.
PMID- 27612577
TI - The context of context: Examining the associations between healthy and unhealthy
measures of neighborhood food, physical activity, and social environments.
AB - Multilevel health research often focuses on a singular dimension of the
neighborhood environment in relation to individual-level health behaviors (e.g.,
diet, physical activity) and outcomes (e.g., obesity). This study examined
associations between healthy and unhealthy neighborhood features across food,
physical activity, and social environments. We used neighborhood-level (i.e.,
census block group) access (0/1) measures of the 1) food (grocery store,
convenience store, fast food restaurant), 2) physical activity
(fitness/recreation facility, park), and 3) social (crime, renter occupancy)
environments to capture both healthy and unhealthy neighborhood features for a
sample of neighborhoods (n=126) in East Baton Rouge Parish, Louisiana, United
States. We employed a) bivariate correlations, or spatial regression where
necessary, to identify significant associations between neighborhood access
measures; and b) two-step cluster analysis to identify neighborhood typologies
based upon neighborhood access measures. Results demonstrated multiple
significant associations between healthy and unhealthy access measures across the
three neighborhood environments. Cluster analysis further confirmed that
neighborhoods are not completely healthy or unhealthy, but rather can be
characterized by neighborhood features that are both health-promoting and health
constraining. This study elucidates a 'context of context' whereby no singular
aspect of a neighborhood completely explains health in individuals. Rather, in
order to effectively model the association between neighborhood and individual
level health, it may be necessary to account for the inter-related nature of
neighborhood features.
PMID- 27612578
TI - Adherence to dietary guidelines as a protective factor against chronic or
recurrent depressive symptoms in the French SU.VI.MAX cohort.
AB - Several studies have suggested that a healthier overall diet was associated with
a lower risk of depression, which is one of the main causes of disability
worldwide. Our objective was to investigate the prospective association of
adherence to dietary guidelines at midlife, measured by the French Programme
National Nutrition Sante-Guideline Score (PNNS-GS), with chronic or recurrent
depressive symptoms. The association between the PNNS-GS and chronic or recurrent
depressive symptoms was evaluated among participants of the French
Supplementation en Vitamines et Mineraux AntioXydants (SU.VI.MAX) cohort with
available data on the PNNS-GS at baseline (1994-1996) and on the Center for
Epidemiologic Studies-Depression Scale (CES-D) in 1996-1997 and follow-up (2007
2009) (n=3328). Chronic or recurrent depressive symptoms were defined by a CES-D
score >=16 at baseline and follow-up. Odds ratios (OR) and 95%-confidence
intervals (95%-CI) were estimated across quartiles (Q) of the PNNS-GS, using
logistic regression models. In our study, 10.1% of the participants (n=335) had
chronic or recurrent depressive symptoms. After adjustment for potential
confounders, the PNNS-GS was inversely associated with chronic or recurrent
depressive symptoms: ORQ4 vs. Q1: 0.42 (95%-CI: 0.29, 0.60). Modelling the PNNS
GS as a continuous variable yielded similar results: OR for a 1-point increment
in the PNNS-GS: 0.86 (95%-CI: 0.80, 0.92). In conclusion, higher adherence to
French dietary guidelines at midlife was associated with a lower rate of chronic
or recurrent depressive symptoms, which suggests that these recommendations may
be highly relevant, not only to avoid chronic diseases, but also for the overall
well-being.
PMID- 27612579
TI - Physical activity and quality of life in older women with a history of depressive
symptoms.
AB - Physical activity (PA) is positively associated with health-related quality of
life (HRQL) in older adults. It is not evident whether this association applies
to older adults with poor mental health. This study examined associations between
PA and HRQL in older women with a history of depressive symptoms. Participants
were 555 Australian women born in 1921-1926 who reported depressive symptoms in
1999 on a postal survey for the Australian Longitudinal Study on Women's Health.
They completed additional surveys in 2002, 2005 and 2008 that assessed HRQL and
weekly minutes walking, in moderate PA, and in vigorous PA. Random effects mixed
models were used to examine concurrent and prospective associations between PA
and each of 10 HRQL measures (eight SF-36 subscales; two composite scales). In
concurrent models, higher levels of PA were associated with better HRQL
(p<0.001). The strongest associations were found for the bodily pain, physical
functioning, general health perceptions, social functioning and vitality
measures. Associations were attenuated in prospective models, more so for mental
HRQL-related scales than for physical HRQL-related scales. However, strong
associations (>3 point differences) were evident for physical functioning,
general health, vitality and social functioning. For women in their 70s-80s with
a history of depressive symptoms, PA is positively associated with HRQL
concurrently, and to a lesser extent prospectively. This study extends previous
work by showing significant associations in older women with a history of
depressive symptoms. Incorporating PA into depression management of older women
may improve their HRQL.
PMID- 27612580
TI - The impact of access to health services on prediabetes awareness: A population
based study.
AB - Research demonstrates that prediabetes awareness has important implications for
participation in diabetes risk-reducing behaviors. We examined the impact of
levels of access to health services on prediabetes awareness. In 2016, we
conducted an analysis among U.S. adults with prediabetes using cross-sectional
data from three cycles (2007-2008, 2009-2010, and 2011-2012) of the National
Health and Nutrition Examination Survey. Participants aware and unaware of their
prediabetes were classified as having full, partial, or no access to health
services based on current health insurance coverage and having a routine place to
go for health care. Multivariable logistic regression was used to estimate the
association between access to health services and prediabetes awareness. Among a
total sample of 2999U.S. adults with prediabetes, an estimated 92.0% were unaware
of their prediabetes status. Participants that were unaware of their prediabetes
tended to be younger, male, and were less likely to be obese or have a family
history of diabetes. Having no access to health services significantly increased
the odds of being prediabetes unaware (AOR: 2.65; 95% CI: 1.10-6.38). However,
participants with insurance but no place of regular care had the greatest odds of
being prediabetes unaware (AOR: 3.21; 95% CI: 1.21-8.55). These findings suggest
that access to health services is a key factor for prediabetes awareness. Health
policies and interventions should strive to ensure equitable access to health
services in order to detect prediabetes, and promote awareness and engagement in
risk-reducing behaviors to decrease the incidence of diabetes.
PMID- 27612582
TI - High-resolution structural and elemental analyses of calcium storage structures
synthesized by the noble crayfish Astacus astacus.
AB - During premolt, crayfish develop deposits of calcium ions, called gastroliths, in
their stomach wall. The stored calcium is used for the calcification of parts of
the skeleton regularly renewed for allowing growth. Structural and molecular
analyses of gastroliths have been primarily performed on three crayfish species,
Orconectes virilis, Procambarus clarkii, and more recently, Cherax
quadricarinatus. We have performed high-resolution analyses of gastroliths from
the native noble crayfish, Astacus astacus, focusing on the microstructure, the
mineralogical and elemental composition and distribution in a comparative
perspective. Field emission scanning electron microscopy (FESEM) and atomic force
microscopy (AFM) observations showed a classical layered microstructure composed
of 200-nm diameter granules aligned along fibers. These granules are themselves
composed of agglomerated nanogranules of 50nm-mean diameters. Denser regions of
bigger fused granules are also present. Micro-Raman spectroscopy show that if A.
astacus gastroliths, similarly to the other analyzed gastroliths, are mainly
composed of amorphous calcium carbonate (ACC), they are also rich in amorphous
calcium phosphate (ACP). The presence of a carotenoid pigment is also observed in
A. astacus gastrolith contrary to C. quadricarinatus. Energy-dispersive X-ray
spectroscopy (EDX) analyses demonstrate the presence of minor elements such as
Mg, Sr, Si and P. The distribution of this last element is particularly
heterogeneous. X-ray absorption near edge structure spectroscopy (XANES) reveals
an alternation of layers more or less rich in phosphorus evidenced in the mineral
phase as well as in the organic matrix in different molecular forms. Putative
functions of the different P-comprising molecules are discussed.
PMID- 27612581
TI - Structures of type IV pilins from Thermus thermophilus demonstrate similarities
with type II secretion system pseudopilins.
AB - Type IV pilins are proteins which form polymers that extend from the surface of
the bacterial cell; they are involved in mediating a wide variety of functions,
including adhesion, motility and natural competence. Here we describe the
determination of the crystal structures of three type IVa pilins proteins from
the thermophile Thermus thermophilus. They form part of a cluster of pilus-like
proteins within the genome; our results show that one, Tt1222, is very closely
related to the main structural type IV pilin, PilA4. The other two, Tt1218 and
Tt1219, also adopt canonical pilin-like folds but, interestingly, are most
closely related to the structures of the type II secretion system pseudopilins,
EpsI/GspI and XcpW/GspJ. GspI and GspJ have been shown to form a complex with
another pseudopilin, GspK, and this heterotrimeric complex is known to play a key
role in initiating assembly of a pseudopilus which is thought to drive the
secretion process. The structural similarity of Tt1218 and Tt1219 to GspI and
GspJ suggests that they might work in a similar way, to deliver functions
associated with type IV pili in T. thermophilus, such as natural competence.
PMID- 27612583
TI - Cancer-related fatigue in patients with and survivors of Hodgkin's lymphoma: a
longitudinal study of the German Hodgkin Study Group.
AB - BACKGROUND: Patients with Hodgkin's lymphoma might have persistent fatigue even
years after treatment. However, knowledge of the development of fatigue
persisting long after completion of treatment is limited. Therefore, we did a
detailed analysis of fatigue in our first-line clinical trials for early-stage
favourable (HD13 trial), early-stage unfavourable (HD14 trial), and advanced
stage (HD15 trial) Hodgkin's lymphoma. Beyond the description of fatigue from
diagnosis up to 5 years after treatment, we aimed to assess any effect of patient
characteristics, disease characteristics, or treatment characteristics on
persistent fatigue. METHODS: In this longitudinal study, we included patients
with early-stage favourable, early-stage unfavourable, and advanced-stage
Hodgkin's lymphoma from the HD13, HD14, and HD15 trials, respectively, aged
between 18 and 60 years. Eligible patients for these trials had newly diagnosed,
histologically proven Hodgkin's lymphoma, an Eastern Cooperative Oncology Group
performance status of 2 or lower, HIV negativity, and absence of comorbidity
disallowing protocol treatment. We used the fatigue scale of the European
Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
to assess fatigue from diagnosis up to 5 years after the end of treatment. The
primary outcomes of interest in this study were fatigue scores in the second and
fifth year after end of treatment. We estimated the effect of different disease,
patient, and treatment characteristics on fatigue with multiple regression
analyses and identified fatigue trajectories with growth mixture models. The
regression analyses and growth mixture models used robust and full information
maximum likelihood estimates to account for missing data. The HD13, HD14, and
HD15 trials are registered as international standard randomised controlled
trials, ISRCTN63474366, ISRCTN04761296, and ISRCTN32443041, respectively.
FINDINGS: The HD13 trial enrolled patients with early-stage favourable disease
from Jan 28, 2003, to Sept 30, 2009; the HD14 trial enrolled patients with early
stage unfavourable disease from Jan 28, 2003, to Dec 23, 2009; and the HD15 trial
enrolled patients with advanced-stage disease from Jan 28, 2003, to April 18,
2008. 5306 patients were enrolled in these trials. We analysed 4215 patients with
any valid fatigue assessment up to 5 years after the end of treatment. Patients
with higher tumour burden at diagnosis had more fatigue at baseline (mean fatigue
score in HD13: 30.8 [SD 28.0]; in HD14: 39.8 [29.4], and in HD15: 49.0 [30.2]).
Fatigue scores (FA) in the second year after the end of treatment were 28.5
(24.7) in HD13, 28.8 (24.4) in HD14, and 30.7 (24.4) in HD15; in the fifth year
after the end of treatment FA was 30.8 (26.0) in HD13, 27.1 (24.8) in HD14, and
28.2 (24.9) in HD15. Predictors of fatigue in the second and fifth year after end
of treatment were baseline fatigue (p<0.0001) and age as a continuous variable
(p<0.0001). In addition to preceding fatigue and age, patient sex and Hodgkin's
lymphoma specific risk factors at baseline did not consistently and significantly
improve the prognosis of fatigue in the first, second, and fifth year after end
of treatment. There was no significant effect of treatment on fatigue scores in
the second and fifth year after treatment. INTERPRETATION: Our findings show a
high incidence of severe acute and persistent fatigue in Hodgkin's lymphoma
survivors, which is largely independent of tumour stage and treatment. Our
results contribute to a better understanding of fatigue in patients with
Hodgkin's lymphoma and Hodgkin's lymphoma survivors and could inform development
of urgently needed intervention strategies. FUNDING: Deutsche Krebshilfe.
PMID- 27612584
TI - Does persistent fatigue in survivors relate to cancer?
PMID- 27612585
TI - Nasal conchae function as aerodynamic baffles: Experimental computational fluid
dynamic analysis in a turkey nose (Aves: Galliformes).
AB - We tested the aerodynamic function of nasal conchae in birds using CT data from
an adult male wild turkey (Meleagris gallopavo) to construct 3D models of its
nasal passage. A series of digital "turbinectomies" were performed on these
models and computational fluid dynamic analyses were performed to simulate
resting inspiration. Models with turbinates removed were compared to the
original, unmodified control airway. Results revealed that the four conchae found
in turkeys, along with the crista nasalis, alter the flow of inspired air in ways
that can be considered baffle-like. However, these baffle-like functions were
remarkably limited in their areal extent, indicating that avian conchae are more
functionally independent than originally hypothesized. Our analysis revealed that
the conchae of birds are efficient baffles that-along with potential heat and
moisture transfer-serve to efficiently move air to specific regions of the nasal
passage. This alternate function of conchae has implications for their evolution
in birds and other amniotes.
PMID- 27612586
TI - Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy
subjects and COPD patients.
AB - PURPOSE: To determine whether the analysis of the slow expiratory transpulmonary
pressure-volume (PL-V) curve provides an alternative to the single-breath
nitrogen test (SBN) for the assessment of the closing volume (CV). METHODS: SBN
test and slow deflation PL-V curve were simultaneously recorded in 40 healthy
subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test
(CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the
exponential fit (CVexp), and b) inflection point of the interpolating sigmoid
function (CVsig). RESULTS: In the absence of phase IV, COPD patients exhibited a
clearly discernible inflection in the PL-V curve. In the presence of phase IV,
CVSBN and CVexp coincided (CVSBN/CVexp=1.04+/-0.04 SD), whereas CVsig was
systematically larger (CVsig/CVexp=2.1+/-0.86). CONCLUSION: The coincidence
between CVSBN and CVexp, and the presence of the inflection in the absence of
phase IV indicate that the deviation of the PL-V curve from the exponential fit
reliably assesses CV.
PMID- 27612588
TI - Doulas for surgical management of miscarriage and abortion: a randomized
controlled trial.
AB - BACKGROUND: Women undergoing office-based surgical management of a failed or
undesired pregnancy often report fear of pain and anxiety pertaining to the
procedure. Doulas are trained to specifically address women's physical and
emotional needs in obstetric care, and recently have extended their practice to
support women through all pregnancy outcomes. OBJECTIVE: We sought to evaluate
the impact of doulas on patients' physical and emotional responses to surgical
management of a first-trimester failed or undesired pregnancy under local
anesthesia. STUDY DESIGN: In this nonblinded, randomized trial, women received
doula support or routine care during office uterine aspiration for failed or
unwanted pregnancies in the first trimester. The primary outcome was pain
measured on a 100-mm visual analog scale. Secondary outcomes included
satisfaction, emotional state, sense of personal empowerment, and ability to cope
immediately and 1 month after the procedure, as well as medical assistants'
assessment of the doula's utility. A sample size of 35 per group (N = 70) was
planned to detect a 20% difference in pain score. RESULTS: From April 2014
through January 2015, 129 women were screened and 70 were randomized. The 2 study
groups were similar on all baseline characteristics. The primary outcome was not
different between the doula and control groups (pain score 70.7 +/- 24.5 mm vs
59.7 +/- 32.5 mm, P = .11, respectively), even after controlling for procedure
indication (P = .20). While 97% of women who received doula support reported this
helped with their experience, there was no statistically significant difference
in satisfaction, emotional response, sense of empowerment, or perceived ability
to cope between the 2 groups of women immediately following or 1 month after the
procedure. Of all study participants, 72% reported that it was important to have
someone with them during the procedure, but that the support person did not have
to be a doula. CONCLUSION: Doula support during office uterine aspiration for
failed or undesired pregnancies is well received and desired by women undergoing
this procedure despite no significant effect on physical comfort or emotional
responses related to the procedure. This may suggest an unmet psychosocial need
for procedure-related support among such women.
PMID- 27612590
TI - Novel microRNA revealed by systematic analysis of the microRNA transcriptome in
dentate gyrus granule cells.
AB - Post-transcriptional control of gene expression by microRNAs provides an
important regulatory system within neurons, allowing co-ordinate and fine-tuned
expression of plasticity-related proteins. Indeed, specific microRNAs have been
shown to be regulated by synaptic activity in the dentate gyrus, and contribute
to the regulated gene expression that underlies the persistence of long-term
potentiation (LTP), a model of memory. To fully explore the contribution of
microRNAs in synaptic plasticity, it is important to characterize the complete
microRNA transcriptome in regions such as the dentate gyrus. Accordingly we used
deep sequencing and miRDeep* analysis to search for novel microRNAs expressed in
the dentate gyrus granule cell layer. Drawing on combined sequencing and
bioinformatics analyses, including hairpin stability and patterns of precursor
microRNA processing, we identified nine putative novel microRNAs. We did not find
evidence of differential expression of any of these putative microRNAs following
LTP at perforant path-granule cell synapses in awake rats (5h post-tetanus;
p>0.05). Focusing on novel_miR-1, the most abundant novel miRNA, we showed that
this sequence could be amplified from RNA extracted from dentate gyrus granule
cells by reverse transcription-quantitative polymerase chain reaction. Further,
by computationally predicting mRNA targets of this microRNA, we found that this
novel microRNA likely contributes to the regulation of proteins that function at
synapses.
PMID- 27612587
TI - Respiratory-swallowing coordination in normal subjects: Lung volume at swallowing
initiation.
AB - This study was designed to investigate the significance of bolus types and
volumes, delivery methods and swallowing instructions on lung volume at
swallowing initiation in normal subjects in a single experiment using a
multifactorial approach. Our broad range goal was to determine optimal lung
volume range associated with swallowing initiation to provide training targets
for dysphagic patients with disordered respiratory-swallow coordination. Our
hypothesis was that swallows would be initiated within a limited range of quiet
breathing lung volumes regardless of bolus volume, consistency or task. Results
confirmed this hypothesis and revealed that swallows were initiated at mean lung
volume=244ml. Cued swallows were initiated at lower quiet breathing volumes than
un-cued swallows (cued=201ml; un-cued=367ml). Water boluses were initiated at
slightly higher quiet breathing volumes than solids. Data suggest that swallows
occur within a restricted range of lung volumes with variation due to
instructions, bolus type and other experimental variables.
PMID- 27612589
TI - Human Embryos Created by Embryo Splitting Secrete Significantly Lower Levels of
miRNA-30c.
AB - Studies reporting term pregnancy and the production of genetically identical
offspring from isolated blastomeres of early stage embryos have been carried out
in small and large animals. However, very little is known about the effects of
embryo splitting on the development and reproductive competency of human embryos.
In this study, we investigated the effects of embryo splitting on profile of
microRNAs (miRNAs) detected in their spent blastocyst medium (SBM) by comparative
analysis of miRNA profiles in SBM of human twin embryos created by blastomere
biopsy and SBM of blastocysts that resulted in a healthy pregnancy and live birth
following embryo transfer. The profile of miRNA secretion in in vitro culture
media consistently distinguishes twin from control embryos. We found that six
miRNAs are significantly more abundant in SBM from twin embryos, while nine are
significantly more abundant in SBM from euploid implanted blastocysts. These nine
include miRNA-30c, a previously reported marker of blastocyst implantation
potential. Furthermore, 22.9% of miRNAs secreted by twin embryos were never
detected in SBM from normal reproductively competent blastocysts, or from
trophectoderm (TE) samples from normal blastocysts donated for the research. The
miRNA profile, unique to twin blastocysts, might be a result of differential
lineage commitment in these embryos.
PMID- 27612591
TI - Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt
Jakob Disease Patients.
AB - Human prion diseases are neurodegenerative disorders caused by abnormally folded
prion proteins in the central nervous system. These proteins can be detected
using the quaking-induced conversion assay. Compared with other bioassays, this
assay is extremely sensitive and was used in the present study to determine prion
distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although
infectivity of the sporadic form is thought to be restricted within the central
nervous system, results showed that prion-seeding activities reach 106/g from a
50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity
exists in non-neural organs, and we suggested that non-neural tissues of 106/g
SD50 did not exist the infectivity.
PMID- 27612592
TI - Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the
Identification of Signature Immunohistochemical Markers for Clinical Use.
AB - BACKGROUND: It has been suggested that bladder cancer can be divided into two
molecular subtypes referred to as luminal and basal with distinct clinical
behaviors and sensitivities to chemotherapy. We aimed to validate these subtypes
in several clinical cohorts and identify signature immunohistochemical markers
that would permit simple and cost-effective classification of the disease in
primary care centers. METHODS: We analyzed genomic expression profiles of bladder
cancer in three cohorts of fresh frozen tumor samples: MD Anderson (n=132), Lund
(n=308), and The Cancer Genome Atlas (TCGA) (n=408) to validate the expression
signatures of luminal and basal subtypes and relate them to clinical follow-up
data. We also used an MD Anderson cohort of archival bladder tumor samples (n=89)
and a parallel tissue microarray to identify immunohistochemical markers that
permitted the molecular classification of bladder cancer. FINDINGS: Bladder
cancers could be assigned to two candidate intrinsic molecular subtypes referred
to here as luminal and basal in all of the datasets analyzed. Luminal tumors were
characterized by the expression signature similar to the intermediate/superficial
layers of normal urothelium. They showed the upregulation of PPARgamma target
genes and the enrichment for FGFR3, ELF3, CDKN1A, and TSC1 mutations. In
addition, luminal tumors were characterized by the overexpression of E-Cadherin,
HER2/3, Rab-25, and Src. Basal tumors showed the expression signature similar to
the basal layer of normal urothelium. They showed the upregulation of p63 target
genes, the enrichment for TP53 and RB1 mutations, and overexpression of CD49,
Cyclin B1, and EGFR. Survival analyses showed that the muscle-invasive basal
bladder cancers were more aggressive when compared to luminal cancers. The
immunohistochemical expressions of only two markers, luminal (GATA3) and basal
(KRT5/6), were sufficient to identify the molecular subtypes of bladder cancer
with over 90% accuracy. INTERPRETATION: The molecular subtypes of bladder cancer
have distinct clinical behaviors and sensitivities to chemotherapy, and a simple
two-marker immunohistochemical classifier can be used for prognostic and
therapeutic stratification. FUNDING: U.S. National Cancer Institute and National
Institute of Health.
PMID- 27612594
TI - Amphotericin B lipid complex in the treatment of severe paracoccidioidomycosis: a
case series.
AB - Amphotericin B deoxycholate is the main option for intravenous (i.v.) treatment
of severe paracoccidioidomycosis (PCM). This is the first report of amphotericin
B lipid complex (ABLC) in the treatment of PCM. Among 28 patients, cure was
achieved in all patients (100%) using ABLC. Mean and median daily doses of ABLC
were 3.39 mg/kg/day and 3.35 mg/kg/day, respectively. ABLC may be a choice in the
treatment of severe forms of PCM or when i.v. options are required.
PMID- 27612595
TI - Changes in HbA1c levels and body mass index after successful decompression
surgery in patients with type 2 diabetes mellitus and lumbar spinal stenosis:
results of a 2-year follow-up study.
AB - BACKGROUND CONTEXT: Lumbar spinal stenosis (LSS) can hinder a patient's physical
activity, which in turn can impair glucose tolerance and body weight regulation
in patients with type 2 diabetes mellitus (DM-2). Therefore, successful lumbar
surgery could facilitate glycemic control and body weight regulation. PURPOSE:
This study aimed to evaluate the effects of postoperative improvement in physical
activity on body mass index (BMI) and hemoglobin A1c (HbA1c) level in patients
with LSS and DM-2 over a 2-year follow-up period. STUDY DESIGN: Prospective
longitudinal observational study. PATIENT SAMPLE: Patients with LSS and DM-2.
OUTCOME MEASURES: Visual analogue scale (VAS) scores for back pain and leg pain,
Oswestry Disability Index (ODI) scores, Japanese Orthopaedic Association (JOA)
scores, JOA Back Pain Evaluation Questionnaire (JOABPEQ) sections, BMI, and blood
analysis for HbA1c were carried out. METHODS: A total of 119 patients were
enrolled for analysis of the effect of successful decompression surgery on
changes in HbA1c levels and BMI. The VAS score, ODI score, JOA score, JOABPEQ,
BMI, HbA1c were reassessed at 6 months, 1 year, and 2 years after surgery.
Additionally, correlations between changes in HbA1c and changes in the ODI, JOA,
JOABPEQs, and BMI were analyzed. RESULTS: The overall values of HbA1c before and
at 6 months, 1 year, and 2 years after the surgery were 7.08+/-0.94%, 6.58+/
0.87%, 6.59+/-0.79%, and 6.59+/-0.79%, respectively (p-values; 6 months: .024; 1
year: .021; 2 years: .038). In the not well-controlled sugar (non-WCS) group
(preoperative HbA1c>6.5%), the difference between pre- and postoperative HbA1c
was highly statistically significant (p<.01). The overweight group (preoperative
BMI>=25) showed statistically significant BMI reduction in the second year after
surgery (p=.034). The postoperative HbA1c changes are strongly correlated with
the improvements of ODI, JOA, and JOABPEQ after surgery. CONCLUSIONS: The present
study demonstrates that in patients with DM-2 and LSS, successful lumbar surgery
may facilitate glycemic control by enabling an increase in the patient's level of
physical activity. Additionally, it could help reduce body weight in overweight
(BMI>25) patients with DM-2 and LSS.
PMID- 27612593
TI - Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus
Neutralization Sensitivity.
AB - Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly
sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization
resistant (tier-2) viruses, but no vaccine has induced antibodies that can
broadly neutralize heterologous tier-2 viruses. In this study, we isolated
antibodies from an HIV-1-infected individual that targeted the gp41 membrane
proximal external region (MPER) that may have selected single-residue changes in
viral variants in the MPER that resulted in neutralization sensitivity to
antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change
in the MPER in a second virus from another infected-individual also conferred
enhanced neutralization sensitivity. These gp41 single-residue changes thus
transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine
elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino
acid changes within the MPER bnAb epitope of naturally-selected escape viruses
can increase neutralization sensitivity to multiple types of neutralizing
antibodies, and underscore the critical importance of the MPER for maintaining
the integrity of the tier-2 HIV-1 trimer.
PMID- 27612596
TI - The Impact of Marijuana Legalization on Adolescent Use, Consequences, and
Perceived Risk.
AB - BACKGROUND: Currently, only four states have legalized recreational marijuana use
for adults over 21 years of age. Therefore, little is known about the influence
that legalization will have on adolescent marijuana use. OBJECTIVES: This study
examines how marijuana legalization has impacted the frequency and consequences
of adolescent use in a sample of participants in a school-based, substance use
intervention. We hypothesized that adolescents enrolled in the intervention in
years after marijuana legalization would present with more problematic use
compared to those enrolled prior, and that changes in the perceived risk of
marijuana would be a mechanism of problematic use. METHODS: Participants were 262
students enrolled in a school-based substance use intervention in 2010 to 2015.
The Customary Drinking and Drug Use Record, Alcohol and Drug Use Consequences
Questionnaire, and a decisional balance matrix were used to assess marijuana
frequency, negative consequences, and perceived risk of use. A mediation model
was used to test the degree to which marijuana legalization may lead to increased
frequency and consequences of use through perceived risk. RESULTS: Findings
indicated a significantly positive correlation between marijuana-related
consequences and perceived risk post legalization. Despite relatively equal use
between both groups, adolescents in the legalization group experienced higher
levels of perceived risk and increased negative consequences.
CONCLUSIONS/IMPORTANCE: Due to the rising legalization status of marijuana in the
United States, it is imperative that psychoeducation is provided to adults and
adolescents about the consequences of underage marijuana use.
PMID- 27612597
TI - Phosphoglycerate mutase deficiency (glycogen storage disease X) caused by a novel
variant in PGAM-M.
AB - Phosphoglycerate mutase enzyme deficiency in muscle causes a metabolic myopathy
(glycogen storage disease X) characterized by exertional muscle contractures,
weakness, hyperCKemia, and myoglobinuria. Six different autosomal recessive
variants in PGAM-M have been described thus far (Salameh et al., 2013). In this
case report, we report a novel disease-causing variant. A 52-year-old African
American woman presented with exertional muscle contractures, myalgias, and
weakness since childhood including an episode of rhabdomyolysis. Neurologic
examination and EMG were normal. CK was mildly elevated at rest and over 20,000
U/L during her episode of rhabdomyolysis. Muscle biopsy revealed subsarcolemmal
collections suggestive of tubular aggregates. Phosphoglycerate mutase activity
was 8% of the reference value. PGAM-M sequencing showed compound heterozygous
variants: c.233G>A, which has been found only in African-Americans with this
disease, and a novel variant, c.278G>A. This case expands the genetic spectrum of
phosphoglycerate mutase deficiency.
PMID- 27612598
TI - Diagnosis and treatment of obsessive compulsive behavior in a boy with Duchenne
muscular dystrophy and autism spectrum disorder: A case report.
AB - We describe a case study of comorbid obsessive-compulsive disorder (OCD) in a
nine-year-old boy with Duchenne muscular dystrophy (DMD). Patient history
included persistent deficits in social communication and restrictive and
repetitive patterns of behavior: a diagnosis of autism spectrum was formalized.
Due to serious disruption on social functioning and negative development of the
obsessive behavior we decided to start pharmacotherapy. Fluoxetine 5 mg/day was
started and gradually increased to 20 mg/day. A significant positive effect was
observed by both parents and teacher in daily functioning. Although parents
reported a positive change in mood, formal behavior rating by them did not reveal
a significant effect, reflecting the insensitivity of general behavior rating
scales. However, neuropsychological testing revealed a significant effect. This
case report highlights the diagnostic and therapeutic challenges of complex
neuropsychiatric comorbidities in DMD. It is the first scientific report on
fluoxetine effectiveness in this patient group. Further research is needed.
PMID- 27612599
TI - Ethnobotany of the Balti community, Tormik valley, Karakorum range, Baltistan,
Pakistan.
AB - BACKGROUND: Limited health facilities and malnutrition are major problems in the
Karakorum Range of Northern Pakistan, often resulting in various human disorders.
Since centuries, however, local communities in these areas have developed
traditional methods for treating various ailments and local foods capes that can
be significant for devising public health and nutritional policies. This study
was intended to document the ethnobotanical knowledge of the local peoples in the
Tormik Valley, especially in the medical and food domains. METHODS: Field trips
were undertaken in 14 different villages of the study area from 2010 to 2012.
Ethnobotanical data were gathered using semi-structured interviews and group
conversation with 69 informants. Details about local uses of plant species were
recorded along with demographic characteristics of the visited communities.
Relative frequency citation index (RFCi) and preference ranking index (PRi) tools
were applied to determine the cultural significance of the reported species.
RESULTS: Sixty-three plant species, with a predominance of Asteraceae and
Fabaceae family members, as well as their detailed folk uses were documented.
Forty-three percent of the species were used to treat various diseases, 21 % were
consumed as wild fruits and vegetables and 53 % of the species had multipurpose
applications. Thymus linearis Benth, Hippophae rhamnoides ssp. turkestanica L.
and Convolvulus arvensis L. were found to be the most utilized medicinal plant
species, i.e. those with significant RFCi values (0.54, 0.51 and 0.48,
respectively). Betula utilis D. Don was the most versatile taxon (seven different
ways of utilization); being this species a common and easily accessible subalpine
tree and then under anthropogenic pressure, the implementation of concrete
strategies aimed at its in-situ and ex-situ conservation is strongly recommended.
CONCLUSION: The valleys in the Karakorum Mountains in the Northern Pakistan host
significant Traditional Knowledge on local food and medicinal plant species,
which need to be reconsidered and cautiously re-evaluated by
ethnopharmacologists, and public health/nutrition actors. Furthermore, germane
trans-disciplinary investigations are suggested to ensure the dynamic
conservation of precious local knowledge systems, as well as plant diversity in
Pakistani mountain regions.
PMID- 27612600
TI - In vitro model of production of antibodies; a new approach to reveal the presence
of key bacteria in polymicrobial environments.
AB - BACKGROUND: There is a rapid emergence of multiple resistant gram-negative
bacteria due to overuse of antibiotics in the treatment of infections. Biofilms
consist of polymicrobial communities that survive the host's defense system. The
key bacteria in biofilms are slow growing and support an attachment and rapid
growth of other microorganisms. Current antimicrobial strategies often fail due
to poor diagnosis of key pathogens in biofilms. The study aims to develop anti
bacterial human antibodies in vitro from patients who had recently undergone a
systemic infection by pathogenic bacteria and to use these antibodies as a tool
for detecting bacteria in biofilms. METHODS: Lymphocytes were separated from
whole blood of patients (n = 10) and stimulated with heat-killed bacteria to
produce antibodies in vitro. The specificity of antibodies in recognizing the
bacteria against which they were directed was evaluated by surface plasmon
resonance system (SPR) and electron microscopy. The ulcer secretions from
patients with chronic and acute leg ulcers and healthy controls were analyzed by
the SPR system and the results were compared with culture studies. RESULTS: The
produced antibodies recognized bacteria with high sensitivity (SPR). The
antibodies against Enterococcus fecalis bound specifically to the microorganism
in a bacterial co-culture that was visualized by electron microscopy. CONCLUSION:
In the present work, a method for producing specific antibodies against bacteria
is introduced to recognize bacterial components in body fluids of patients
suffering from pathogenic biofilms. This diagnostic technique may be most useful
in clinical microbiology and in the choice of antibiotics in the treatment of
serious infections.
PMID- 27612601
TI - Fuzhisan ameliorates Abeta production and tau phosphorylation in hippocampal of
11month old APP/PS1 transgenic mice: A Western blot study.
AB - Accumulation of amyloid-beta (Abeta) peptide and deposition of
hyperphosphorylated tau protein are two major pathological hallmarks of
Alzheimer's disease (AD). Glycogen synthase kinase-3beta (GSK3beta) is
increasingly thought to play a pivotal role in the pathogenesis of AD, both as a
regulator of the production of Abeta and through its well-established role on tau
phosphorylation. The phosphoinositide 3 kinase (PI3K)/Akt pathway plays an import
role in neuronal survival and cognitive function, and is known as an upstream
element of GSK3beta. Fuzhisan (FZS), a Chinese herbal complex prescription, has
been used for the treatment of AD for over 20years, and is known to enhance the
cognitive ability in AD patients as well as in AD model rats. However, it still
remains unclear whether FZS is responsible for regulation of PI3K/AKT/GSK3beta
signaling and contributes to subsequent down-regulation of Abeta and
phosphorylated tau. Thus, we treated APP/PS1 transgenic mice, a useful model of
AD-related memory impairment, with FZS by intragastrical administration for
60days and Donepezil was used as a positive control. The results showed that
treatment with FZS significantly reversed the memory deficit in the Tg APP/PS1
mice in the Morris water maze test. Moreover, FZS significantly attenuated Abeta
production through inhibition of APP procession and phosphorylation of tau in the
hippocampus of Tg APP/PS1 mice. In addition, FZS treatment also increased PI3K
and pSer473-AKT levels, inhibited GSK3beta activity by increasing phosphorylation
of GSK3beta at Ser9. These results indicated that the memory ameliorating effect
of FZS may be, in part, by regulation the PI3K/AKT/GSK3beta signaling which may
contribute to down-regulation of Abeta and tau hyperphosphorylation.
PMID- 27612603
TI - Response to Letter to the Editor on "Balancing Thromboprophylaxis and Bleeding in
Total Joint Arthroplasty: Impact of Eliminating Enoxaparin and Predonation and
Implementing Pneumatic Compression and Tranexamic Acid".
PMID- 27612602
TI - Soluble sortilin is present in excess and positively correlates with progranulin
in CSF of aging individuals.
AB - Mutations in progranulin are a major cause of frontotemporal lobe degeneration
(FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly
reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific
regulation of progranulin levels. Sortilin was recently identified as a
progranulin scavenger receptor that destines it for lysosomal degradation.
Proteolysis or alternative splicing generates soluble sortilin variants that
retain progranulin binding and potentially functions as a decoy receptor. In the
present study, we analyzed soluble sortilin and progranulin in plasma and CSF in
341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold
molar excess compared to progranulin and observed a highly significant positive
correlation between soluble sortilin and progranulin levels in CSF but not in
plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding
sortilin displayed significantly increased soluble sortilin and reduced
progranulin specifically in plasma but not in CSF. Taken together, our findings
suggest that soluble sortilin may affect progranulin levels in both a tissue
specific and genotype-dependent manner.
PMID- 27612604
TI - Predicting the Long-Term Gains in Health-Related Quality of Life After Total Knee
Arthroplasty.
AB - BACKGROUND: We investigated the predictors of long-term gains in quality-adjusted
life years (QALYs) from total knee arthroplasty (TKA) and the patient attributes
that predicted cost-effective TKA. METHODS: Data on TKA patients (n = 570) from
2006 to 2007 were extracted from a single-institution registry. QALY gains over 7
years post surgery were calculated from health-related quality of life (HrQoL)
scores measured preoperatively and annually postoperatively using the short-form
health survey (SF-12) instrument. Multivariate linear regression analysis
investigated the predictors of QALY gain from TKA from a broad range of
preoperative patient characteristics and was used to predict QALY gains for each
individual. Patients were grouped into deciles according to their predicted QALY
gain, and the cost-effectiveness of each decile was plotted on the cost
effectiveness plane. Patient attribute differences between deciles were
decomposed. RESULTS: After exclusions and dropout, data were available for 488
patients. The average estimated QALY gain over 7 years was 0.77 (95% confidence
interval [CI] 0.70-0.83). Predictors significantly associated with smaller QALY
gains were comorbidities (Charlson comorbidity index 3+ coefficient -0.54 CI
0.15 to -0.92), the absence of severe osteoarthritis in the ipsilateral knee (
0.51 CI -0.16 to -0.85), preoperative HrQoL (standardized coefficient -0.34 CI
0.26 to -0.43), the requirement for an interpreter (-0.24 CI -0.05 to -0.44), and
age (-0.01 CI -0.01 to -0.02). The largest difference between cost-effective and
non-cost-effective deciles was relatively high preoperative HrQoL in the non-cost
effective decile. CONCLUSION: TKA is likely to be cost-effective for most
patients except those with unusually high preoperative HrQoL or a lack of severe
osteoarthritis. The poorer outcomes for those requiring an interpreter requires
further research.
PMID- 27612605
TI - Abnormally High Dislocation Rates of Total Hip Arthroplasty After Spinal
Deformity Surgery.
AB - BACKGROUND: The purpose of this study was to determine the prevalence of
concurrent spinopelvic fusion and THA and identify the risk of THA dislocation in
patients with concurrent spinopelvic fusion. METHODS: We retrospectively reviewed
an institutional database of spinal deformity patients and the Humana Inc data
set to identify patients with concurrent THA and spinopelvic fusion. The
prevalence of concurrent THA and spinopelvic fusion was identified, as was the
risk of dislocation for all cohorts. RESULTS: Of 328 patients with spinopelvic
fusions at our institution, 15 patients (4.6%) were found to have concurrent THA.
Similarly, within the Humana database among 1049 patients with spinopelvic
fusion, 4.6% had a concurrent THA. Among the 58,692 THA patients identified, only
0.1% had a concurrent spinopelvic fusion. A THA dislocation was observed in 3 of
15 patients (20.0%) and 3 of 18 THA (16.7%) within our institutional review.
Within the Humana database, 8.3% of patients with THA and spinopelvic fusion went
on to have a dislocation of their THA compared to 2.9% of patients with THA and
no history of spinopelvic fusion (relative risk: 2.9 [1.2-7.6]). CONCLUSION:
Among patients with spinopelvic fusion, the prevalence of concurrent THA is 4.6%,
and among primary THA patients, the prevalence of concurrent spinopelvic fusion
is 0.1%. An alarmingly high THA dislocation rate has been demonstrated among THA
patients with concurrent spinopelvic fusion at our institution (20%) and within a
large national database (8.3%).
PMID- 27612606
TI - Sexual Activity After Total Hip Arthroplasty: A Systematic Review of the
Outcomes.
AB - BACKGROUND: Total hip arthroplasty (THA) may have a marked positive impact on
sexual activity. However, it is unclear how important regaining sexual activity
is for patients undergoing THA or whether surgeons are aware of such concerns.
The purpose of this systematic review was to evaluate the literature on the
effect of THA on sexual activity before and after the procedure and to assess
patient and surgeon perspectives. METHODS: A search of 4 electronic databases
yielded 10 reports between 1970 and 2015. Nine evaluated the effects of THA on
sexual activity in 1694 patients who had a mean age of 57 years (range 17-98
years). Two studies evaluated the perspective of 337 surgeons. Metrics evaluated
included differences in patient and surgeon perspectives, improvements in sexual
activity, and differences in outcomes between men and women. RESULTS: Seventy-six
percent of patients identified hip arthritis as the primary cause of sexual
problems with pain and stiffness being the most common complaints. Post THA, 44%
of patients reported improvements in sexual satisfaction while 27% reported
increased intercourse frequency. Patients returned to sexual activity at a mean 4
month post-THA. Eighty-six percent of surgeons rarely or never discuss sexual
activity with their patients, and 61% believed that patients can resume sexual
activity 1-month post-THA with many agreeing that certain positions were safer.
CONCLUSION: The outcomes of this systematic review suggest that THA is associated
with improved sexual activities and is an important topic for patients. However,
surgeons may spend less time than is desired by the patients on this subject pre-
and post-THA.
PMID- 27612607
TI - A Comparison of Radiographic Outcomes After Total Hip Arthroplasty Between the
Posterior Approach and Direct Anterior Approach With Intraoperative Fluoroscopy.
AB - BACKGROUND: Radiographic outcomes after total hip arthroplasty (THA) have been
linked to clinical outcomes. The direct anterior approach (DAA) for THA has been
criticized by some for providing limited exposure and compromised implant
position but allows for routine use of intraoperative fluoroscopy. We sought to
determine whether radiographic measurements differed by THA approach using
prospective cohorts. METHODS: Two reviewers blinded to surgical approach examined
194 radiographs, obtained 4-6 weeks after primary THA, and obtained measurements
for acetabular inclination angle, acetabular anteversion, radiographic limb
length discrepancy (LLD), and femoral offset. All surgeries were performed at a
tertiary academic medical center in rural New England by an experienced
fellowship-trained arthroplasty surgeon. Measurements for inclination angle,
anteversion, LLD, and offset were made into binary yes/no responses based on
whether the mean measurement (between the 2 reviewers) was acceptable or not
based on established criteria. Multivariate logistic regression analyses were
performed using preoperative and intraoperative characteristics to identify
predictors of acceptability for each measurement. RESULTS: The DAA group had
higher rates of acceptable acetabular angle (96 vs 85%, P = .005) and was
protective against an unacceptable angle in an adjusted predictive model (odds
ratios 0.16, P = .005). There were no significant differences between approaches
for acceptable anteversion, LLD, or offset. Body mass index of 30-34 was
associated with higher odds of unacceptable inclination angle compared to the
nonobese group (adjusted odds ratio, 6.82, P = .013). CONCLUSION: DAA for THA was
associated with lower odds of unacceptable inclination angle compared to the
posterior approach, with no differences in anteversion, LLD, or offset.
PMID- 27612608
TI - Femoral Head Size is Correlated With Head Position in Very Elderly Patients.
AB - BACKGROUND: In cases of femoral neck fracture, it is often not possible to
accurately determine the original position of the head center to assess
appropriate restoration of leg length. The aim of this study was to determine the
accuracy of predicting the position of the femoral head center based on new and
established correlations between the femoral head diameter (FHD) and the distance
between the lesser trochanter and the femoral head center (LT-FHC) in the very
elderly (aged >=80 years) as the mainly affected but yet underinvestigated group.
METHODS: The FHD and the LT-FHC distance were determined in 148 subjects (104
males, 44 females); 90 aged >=80 years and 58 aged <80 years. For each age and
gender subgroup one specific (LT-FHC)/FHD ratio was determined. The accuracy of
the new determined ratios and the established ratios by others were compared by
recalculating the LT-FHC distance of each individual subject. RESULTS: The FHD
and the LT-FHC were significantly correlated, most strongly in elderly females (R
= 0.554, P < .001). Using the new age- and gender-specific ratios, the LT-FHC
distance could be predicted within 10 mm of the true value in 95% of the cases
and in only 77% using previously reported formulas. CONCLUSION: Age- and gender
specific formulas yield higher accuracy than generic formulas. The formulas
presented in this study can offer a practical, easy to use instrument for
orthopedic surgeons performing hip arthroplasty in very elderly patients in
addition to classic techniques to prevent significant leg-length discrepancy.
PMID- 27612609
TI - Super Obesity Is an Independent Risk Factor for Complications After Primary Total
Hip Arthroplasty.
AB - BACKGROUND: Recent studies have reported higher postoperative complication rates
in obese and morbidly obese patients undergoing total hip arthroplasty (THA).
Less data are available regarding super-obese (body mass index [BMI] >50 kg/m2)
patients. This study aims to quantify the risk of complications after THA in
super-obese patients on a national scale and to put these risks in context by
comparing them to patients of other BMI classes as well as those undergoing
revision THA. METHODS: Utilizing a national insurance database, complication
rates after THA in super-obese patients (n = 3244) were compared to nonobese,
obese, and morbidly obese patients undergoing primary THA and all patients
undergoing revision THA. A logistic regression analysis controlling for
demographic and comorbidity variables was utilized to determine the independent
effect of super obesity on complication rates after THA. RESULTS: Super-obese
patients had significantly higher rates of most complications than nonobese,
obese, morbidly obese, and revision THA patients, including venous
thromboembolism, infection, blood transfusion, medical complications,
dislocation, readmission, and revision THA. CONCLUSION: Super-obese patients (BMI
>50 kg/m2) have higher rates of postoperative complications after THA than
nonobese, obese, morbidly obese, and revision THA patients. Super obesity is an
independent risk factor for increased rates of most postoperative complications
including the need for early revision THA.
PMID- 27612610
TI - Antimicrobial-resistant Pseudomonas aeruginosa and Acinetobacter baumannii From
Patients With Hospital-acquired or Ventilator-associated Pneumonia in Vietnam.
AB - PURPOSE: Multidrug-resistant bacterial pathogens are becoming a significant
problem worldwide. Acinetobacter baumannii and Pseudomonas aeruginosa are
problematic multidrug-resistant pathogens. This multicenter study in Vietnam
determined the level of resistance to antimicrobial agents used to treat A
baumannii and P aeruginosa infections in this country. METHODS: Five medical
centers in Vietnam provided 529 P aeruginosa and 971 Acinetobacter species (904 A
baumannii) isolates from patients with hospital-acquired or ventilator-associated
pneumonia from 2012 to 2014. A central laboratory verified identification of the
isolates and performed susceptibility testing using Clinical and Laboratory
Standards Institute methods. FINDINGS: Resistance to cephalosporins, beta
lactam/beta-lactamase inhibitors, carbapenems, and fluoroquinolones was >90%
against A baumannii. Aminoglycosides had only slightly better activity, with
amikacin resistance >80%. Only colistin (MIC90, <=0.25 mg/L) and tigecycline
(MIC90, 4 mg/L) had appreciable activity against A baumannii. Similar activity
was observed among the beta-lactams tested against P aeruginosa. Cefepime
demonstrated the highest activity (60.1% susceptible), which was similar to
doripenem (58.6% susceptible), the most active carbapenem tested. Amikacin was
the most active aminoglycoside tested against P aeruginosa, with susceptibility
of 81.7% compared with tobramycin (58.0%) and gentamicin (56.5%).
Fluoroquinolones had limited activity against P aeruginosa with susceptibility to
ciprofloxacin (55.0%). All P aeruginosa isolates had colistin MIC values <=2
mg/L. IMPLICATIONS: The data from this 3-year longitudinal study in Vietnam
demonstrate that 2 of the most common nonfermentative gram-negative pathogens
associated with hospital-acquired and ventilator-associated pneumonia are
significantly resistant to most of the available treatment options and require
combination therapies unless new antimicrobial agents become available.
PMID- 27612611
TI - Apoptotic pathways and stemness in the colorectal epithelium and lamina propria
mucosae during the human embryogenesis and carcinogenesis.
AB - AIM: Programmed cell death is essential both during normal organ development and
carcinogenesis. In this study we immunohistochemically analyzed different
pathways of cell death in 11 human conceptuses 5th-10th-weeks old, 10 low and
high grade colorectal carcinomas (CRC), and 10 normal colon samples by using
markers for apoptosis (caspase-3, AIF, TUNEL), proliferation (Ki-67) and stemness
(Oct-4). RESULTS: Between the 5th and 10th week of development, caspase-3 and AIF
showed moderate-to-strong expression in the developing gut wall. During
development, number of caspase-3-reactive cells decreased, while AIF increased.
While healthy colorectal control and low grade CRC showed moderate expression of
caspase-3 and AIF, in high grade CRC their expression was strong. Tumor tissues
displayed significantly higher number of positive cells than controls.
Occasionally, co-expressing of both markers characterized dying cells. In
developing colon, Oct-4 and Ki-67 showed moderate-to-strong expression, while
some cells co-expressed both markers. Their number decreased in the epithelium
and increased in the connective tissue in later development. Healthy colorectal
control displayed moderate Ki-67 and mild Oct-4 reactivity. While in low-grade
CRC expression Oct-4 and Ki-67 was moderate, in high-grade CRC their expression
was strong. Although Oct-4 and TUNEL occasionally co-expressed in all samples,
both grades of CRC contained cells that were Oct-4 positive only. CONCLUSION: Our
study revealed two different parallel pathways of cell death, with characteristic
increase of AIF-mediated apoptosis when compared to caspase-3, and presence of
stemness cells both during colon development and carcinogenesis. These finding
might be considered as important diagnostic, survival and CRC therapy predictors.
PMID- 27612612
TI - Reciprocal localization of transcription factors YY1 and CP2c in spermatogonial
stem cells and their putative roles during spermatogenesis.
AB - Maintaining stemness and permitting differentiation mediated by combinations of
transcription factors (TFs) are key aspects of mammalian spermatogenesis. It has
been established that yin yang 1 (YY1), a target factor of mammalian polycomb
repressive complex 2 (PRC2) and a regulator of stemness, is involved in the
stable maintenance of prophase stage spermatocytes. Recently, we have
demonstrated that the TF CP2c partners with YY1 in some cells to antagonistically
regulate the other protein's function. To date, the functional roles of YY1 and
CP2c in spermatogonial stem cells and their derived germ cells remain unclear.
Here, we investigated the expression of YY1 and CP2c in mouse gonocytes and germ
cells using tissue immunohistochemical and immunofluorescence analyses. At E14.5,
both YY1 and CP2c were stained in gonocytes and Sertoli cells in testicular
cords, showing different proportion and density of immunoreactivity. However, in
adult testes, YY1 was localized in the nuclei of spermatogonial stem cells and
spermatocytes, but not in spermatozoa. It was also detected in spermatogonia and
spermatids in a stage-specific manner during spermatogenic cycle. CP2c could be
detected mostly in the cytoplasm of spermatocytes but not at all in
spermatogonial stem cells, indicating mutually exclusive expression of CP2c and
YY1. Interestingly, however, CP2c was stained in the cytoplasm and nucleus of
spermatogonia at elongation and release stages, and co-localized with YY1 in the
nucleus at grouping, maturation, and releasing stages. Neither YY1 nor CP2c was
expressed in spermatozoa. Our data indicate that YY1 strongly localizes in the
spermatogonial stem cells and co-localizes heterogeneously with CP2c to permit
spermatogenesis, and also suggest that YY1 is essential for stemness of
spermatogonial stem cells (SCs) whereas CP2c is critical for the commitment of
spermatogonia and during the progression of spermatogonia to spermatids. This
evaluation expands our understanding of the molecular mechanism of spermatogonia
formation as well as spermatogenesis in general.
PMID- 27612613
TI - Association of Chemerin and Vascular Endothelial Growth Factor (VEGF) with
Diabetic Nephropathy.
AB - BACKGROUND Diabetic nephropathy (DN) is a common complication of diabetes, caused
by diabetic microvascular lesions. The pathogenesis of DN is complicated,
involving genetics, physics, chemistry, and environmental factors. Chemerin is a
fat cell factor that participates in regulating inflammation. Vascular
endothelial growth factor (VEGF) promotes vascular endothelial cell
proliferation, differentiation, and angiogenesis. The relationship role of
Chemerin and VEGF in DN is not fully understood. MATERIAL AND METHODS SD rats
were randomly divided into 2 groups: the control group and the DN group.
Streptozotocin was used to construct the DN model. Serum creatinine (Scr), blood
urea nitrogen (BUN), and urine microalbumin (UAlb) were detected. Real-time PCR
and Western blot were used to test Chemerin and VEGF mRNA and protein expression
in kidney tissue. ELISA was performed to test TGF-beta1, TNF-alpha, and INF-gamma
levels. The correlation of Chemerin and VEGF with renal function and inflammatory
factors was analyzed. RESULTS DN group rats showed obviously increased Scr and
BUN levels, and elevated TGF-beta1, TNF-alpha, and INF-gamma secretion (P<0.05).
Compared with controls, Chemerin and VEGF were clearly overexpressed in the DN
group (P<0.05). Chemerin and VEGF expression were positively correlated with
inflammatory factors and renal function. CONCLUSIONS Chemerin and VEGF play
important roles in DN by regulating inflammatory factors and renal function. They
may be treated as indicators of DN.
PMID- 27612614
TI - Methodology for identification of pore forming antimicrobial peptides from soy
protein subunits beta-conglycinin and glycinin.
AB - Antimicrobial peptides (AMPs) inactivate microbial cells through pore formation
in cell membrane. Because of their different mode of action compared to
antibiotics, AMPs can be effectively used to combat drug resistant bacteria in
human health. AMPs can also be used to replace antibiotics in animal feed and
immobilized on food packaging films. In this research, we developed a methodology
based on mechanistic evaluation of peptide-lipid bilayer interaction to identify
AMPs from soy protein. Production of AMPs from soy protein is an attractive, cost
saving alternative for commercial consideration, because soy protein is an
abundant and common protein resource. This methodology is also applicable for
identification of AMPs from any protein. Initial screening of peptide segments
from soy glycinin (11S) and soy beta-conglycinin (7S) subunits was based on their
hydrophobicity, hydrophobic moment and net charge. Delicate balance between
hydrophilic and hydrophobic interactions is necessary for pore formation. High
hydrophobicity decreases the peptide solubility in aqueous phase whereas high
hydrophilicity limits binding of the peptide to the bilayer. Out of several
candidates chosen from the initial screening, two peptides satisfied the criteria
for antimicrobial activity, viz. (i) lipid-peptide binding in surface state and
(ii) pore formation in transmembrane state of the aggregate. This method of
identification of antimicrobial activity via molecular dynamics simulation was
shown to be robust in that it is insensitive to the number of peptides employed
in the simulation, initial peptide structure and force field. Their antimicrobial
activity against Listeria monocytogenes and Escherichia coli was further
confirmed by spot-on-lawn test.
PMID- 27612615
TI - Fresh Start, a postpartum weight loss intervention for diverse low-income women:
design and methods for a randomized clinical trial.
AB - BACKGROUND: Overweight and obesity are prevalent among young women and are
greater among minority and low-income women. The postpartum period is critical in
women's weight trajectories as many women do not lose their pregnancy weight, and
others lose some and then plateau or experience weight gain. Excess weight puts
women at greater risk of chronic disease and thus weight loss in the postpartum
period may be key to the long-term health of young women. This paper describes
the design and methods of a randomized clinical trial of Fresh Start, an
innovative narrative-based group intervention aimed at promoting postpartum
weight loss among low-income, diverse women. METHODS/DESIGN: Study participants
were recruited from the five sites of the Women, Infants and Children (WIC)
program in central Massachusetts. Participants were English-speaking, age >= 18
years, 6 weeks to 6 months postpartum, with a body mass index (BMI) >= 27
kg/m(2). The Fresh Start postpartum weight loss intervention, adapted from the
Diabetes Prevention Program (DPP) in collaboration with WIC staff and clients,
consisted of an 8-week group-based curriculum followed by nine monthly telephone
calls. It included a narrative component (i.e., storytelling), group discussions,
print materials and access to exercise facilities. The study is a two-arm
randomized controlled trial. The control condition included print materials and
access to exercise facilities. In-person assessments were conducted at baseline
and at 6 and 12 months following the eight-week intervention phase. DISCUSSION:
The Fresh Start intervention translated key elements of an evidence-based weight
loss protocol into a format that is hypothesized to be relevant, acceptable and
effective for the target audience of low-SES postpartum women. This novel
intervention was developed in collaboration with WIC to be sustainable within the
context of its clinics, which reach approximately 9 million individuals per year
across the U.S. via 10,000 clinics. TRIAL REGISTRATION: clinicaltrials.gov
NCT02176915 . Registered 25 June 2014.
PMID- 27612616
TI - Leaching of arsenic, copper and chromium from thermally treated soil.
AB - Thermal treatment, if properly performed, is an effective way of destroying
organic compounds in contaminated soil, while impact on co-present inorganic
contaminants varies depending on the element. Leaching of trace elements in
thermally treated soil can be altered by co-combusting different types of
materials. This study aimed at assessing changes in mobility of As, Cr and Cu in
thermally treated soil as affected by addition of industrial by-products prior to
soil combustion. Contaminated soil was mixed with either waste of gypsum boards,
a steel processing residue (Fe3O4), fly ash from wood and coal combustion or a
steel abrasive (96.5% Fe0). The mixes and unamended soil were thermally treated
at 800 degrees C and divided into a fine fraction <0.125 mm and a coarse
fraction >0.125 mm to simulate particle separation occurring in thermal treatment
plants. The impact of the treatment on element behaviour was assessed by a batch
leaching test, X-ray absorption spectroscopy and dispersive X-ray spectrometry.
The results suggest that thermal treatment is highly unfavourable for As
contaminated soils as it increased both the As leaching in the fine particle size
fraction and the mass of the fines (up to 92%). Soil amendment with Fe-containing
compounds prior to the thermal treatment reduced As leaching to the levels
acceptable for hazardous waste landfills, but only in the coarse fraction, which
does not justify the usefulness of such treatment. Among the amendments used,
gypsum most effectively reduced leaching of Cr and Cu in thermally treated soil
and could be recommended for soils that do not contain As. Fly ash was the least
effective amendment as it increased leaching of both Cr and As in majority of
samples.
PMID- 27612617
TI - The suitability evaluation of dredged soil from reservoirs as embankment
material.
AB - We assessed the suitability of soil dredged from reservoirs as embankment
material and investigated its physical and geochemical properties and strength
parameters, as well as its environmental stability. The dredged soil samples were
taken from the Ansung, Jechon, and Mulwang Reservoirs in Korea. To evaluate their
environmental stability and geochemical properties, we examined their levels of
heavy metal contamination, pH, and electrical conductivity. We also conducted X
ray fluorescence and X-ray diffraction analyses. Furthermore, we determined the
geotechnical characteristics, such as the compaction characteristics, and
permeability coefficient, and we performed consolidated undrained triaxial
compression tests to evaluate the recycling potential of dredged soil as
embankment material. The concentrations of heavy metals in the sediment samples
were lower than those of the standard samples. The pH value of the soil samples
ranged from 4.25 to 5.39, and the electrical conductivity ranged between 83.3 and
265.0 MUS/cm, indicating suitability for use as construction material with steel
and concrete. Based on the values of the mechanical properties of the dredged
soil, analysis of slope stability was performed for various cases and water level
conditions. Our results indicate that the dredged soil has sufficient stability
for substitution of embankment material and also as new embankment material for
expansion.
PMID- 27612618
TI - European attitudes to water pricing: Internalizing environmental and resource
costs.
AB - Efficient use of the water resource requires internalization of all costs in the
price of water, including environmental and resource costs. However, water
resource management tends to be highly political and increasing water prices are
a sensitive and complicated policy matter. Hence, there is a need for increased
understanding of the implementation process and the attitudes towards
implementation among the general public. This paper explores the spatial
heterogeneity in the public attitude towards internalizing environmental and
resource costs in the price of water across the EU regions. Within an extensive
spatial dataset constructed for the purpose, we estimate the effect of individual
information levels and affordability concerns on the attitude towards
environmental water pricing. Information about water problems is found to have a
significant and positive effect on attitudes as is affordability concern, which
may be explained by expectations of inequity measures to come in place in
parallel with increasing water prices. Overall these results support the
hypothesis that lack of information and affordability concern could lead to
resistance towards efficient water pricing among the general public.
PMID- 27612619
TI - Influence of stenosis on hemodynamic parameters in the realistic left coronary
artery under hyperemic conditions.
AB - The current study investigates the hyperemic flow effects on heamodynamics
parameters such as velocity, wall shear stress in 3D coronary artery models with
and without stenosis. The hyperemic flow is used to evaluate the functional
significance of stenosis in the current era. Patients CT scan data of having
healthy and coronary artery disease was chosen for the reconstruction of 3D
coronary artery models. The diseased 3D models of coronary artery shows a
narrowing of >50% lumen area. Computational fluid dynamics was performed to
simulate the hyperemic flow condition. The results showed that the recirculation
zone was observed immediate to the stenosis and highest wall shear stress was
observed across the stenosis. The decrease in pressure was found downstream to
the stenosis as compared to the coronary artery without stenosis. Our analysis
provides an insight into the distribution of wall shear stress and pressure drop,
thus improving our understanding of hyperemic flow effect under both conditions.
PMID- 27612620
TI - Reply to letter to editor comment on "Cellular and molecular aspects of diabetic
nephropathy; the role of VEGF-A".
PMID- 27612621
TI - Prolonged Ocular Inflammation in Endotoxin-Induced Uveitis in Lysosomal
Phospholipase A2-Deficient Mice.
AB - PURPOSE: The goal of present study was to elucidate the pathophysiological roles
of lysosomal phospholipase A2 (LPLA2) in intraocular pressure (IOP) levels and
ocular inflammation. METHODS: C57BL/6 (wild-type) and LPLA2-deficient mice with
C57BL/6 background were employed. The IOPs were compared between wild-type and
LPLA2-deficient mice during their aging, after topical administration of
antiglaucoma medications such as travoprost, dorzolamide, or timolol maleate, or
after induction of endotoxin-induced uveitis (EIU) using lipopolysaccharide
(LPS). Concerning the EIU, ocular inflammation was also evaluated by
immunohistochemical analysis by the anti-glial fibrillary acidic protein (GFAP)
antibody. RESULTS: The LPLA2-deficient mice showed higher IOP levels than the
wild-type mice until 2 months of age (P = 1.60E-06); in older mice there was no
difference between the two groups. Significant differences in the IOP changes
between groups in young mice were seen after administration of 0.5% timolol (P <
0.05). Upon induction of EIU by LPS, compared with wild-type mice (P < 0.05),
IOPs were significantly elevated in LPLA2-deficient mice at maximum levels of the
ocular inflammation (48 h). Immunohistochemical analysis indicated that LPLA2
deficient mice showed more prolonged expression of GFAP at the inner plexiform
layer and inner nuclear layer by EIU than that found in the wild-type mice (P <
0.05). CONCLUSIONS: These results confirm that LPLA2 plays a significant role in
the control of IOP during mouse ocular development or with ocular inflammation by
facilitating the digestion of intraocular insoluble materials.
PMID- 27612623
TI - Models of midwifery care for Indigenous women and babies: A meta-synthesis.
AB - ISSUE: Indigenous women in many countries experience a lack of access to
culturally appropriate midwifery services. A number of models of care have been
established to provide services to women. Research has examined some services,
but there has not been a synthesis of qualitative studies of the models of care
to help guide practice development and innovations. AIM: To undertake a review of
qualitative studies of midwifery models of care for Indigenous women and babies
evaluating the different types of services available and the experiences of women
and midwives. METHODS: A meta-synthesis was undertaken to examine all relevant
qualitative studies. The literature search was limited to English-language
published literature from 2000-2014. Nine qualitative studies met the inclusion
criteria and literature appraisal - six from Australia and three from Canada.
These articles were analysed for coding and theme development. FINDINGS: The
major themes were valuing continuity of care, managing structural issues, having
negative experiences with mainstream services and recognising success.
DISCUSSION: The most positive experiences for women were found with the services
that provided continuity of care, had strong community links and were controlled
by Indigenous communities. Overall, the experience of the midwifery services for
Indigenous women was valuable. Despite this, there were still barriers preventing
the provision of intrapartum midwifery care in remote areas. CONCLUSION: The
expansion of midwifery models of care for Indigenous women and babies could be
beneficial in order to improve cultural safety, experiences and outcomes in
relation to pregnancy and birth.
PMID- 27612622
TI - Pre-steady-state kinetic investigation of bypass of a bulky guanine lesion by
human Y-family DNA polymerases.
AB - 3-Nitrobenzanthrone (3-NBA), a byproduct of diesel exhaust, is highly present in
the environment and poses a significant health risk. Exposure to 3-NBA results in
formation of N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dGC8-N-ABA), a bulky
DNA lesion that is of particular importance due to its mutagenic and carcinogenic
potential. If not repaired or bypassed during genomic replication, dGC8-N-ABA can
stall replication forks, leading to senescence and cell death. Here we used pre
steady-state kinetic methods to determine which of the four human Y-family DNA
polymerases (hPoleta, hPolkappa, hPoliota, or hRev1) are able to catalyze
translesion synthesis of dGC8-N-ABAin vitro. Our studies demonstrated that
hPoleta and hPolkappa most efficiently bypassed a site-specifically placed dGC8-N
ABA lesion, making them good candidates for catalyzing translesion synthesis
(TLS) of this bulky lesion in vivo. Consistently, our publication (Biochemistry
53, 5323-31) in 2014 has shown that small interfering RNA-mediated knockdown of
hPoleta and hPolkappa in HEK293T cells significantly reduces the efficiency of
TLS of dGC8-N-ABA. In contrast, hPoliota and hRev1 were severely stalled by dGC8
N-ABA and their potential role in vivo was discussed. Subsequently, we determined
the kinetic parameters for correct and incorrect nucleotide incorporation
catalyzed by hPoleta at various positions upstream, opposite, and downstream from
dGC8-N-ABA. Notably, nucleotide incorporation efficiency and fidelity both
decreased significantly during dGC8-N-ABA bypass and the subsequent extension
step, leading to polymerase pausing and error-prone DNA synthesis by hPoleta.
Furthermore, hPoleta displayed nucleotide concentration-dependent biphasic
kinetics at the two polymerase pause sites, suggesting that multiple enzyme*DNA
complexes likely exist during nucleotide incorporation.
PMID- 27612624
TI - Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic
Arch Dissection.
AB - Aortic dissection is an infrequent but important cause of acute ischemic stroke
(AIS), and must not be overlooked because of a possible worse outcome, especially
with the use of an intravenous recombinant tissue plasminogen activator. We
report a case of left carotid artery dissection and AIS originating from
localized aortic arch dissection, pathologically caused by cystic medial necrosis
in the tunica media.
PMID- 27612625
TI - Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on
Follow-Up: How Much Causality Is There?
AB - BACKGROUND: There is increasing debate whether atrial fibrillation (AF) episodes
during follow-up in patients with embolic stroke of undetermined source (ESUS)
are causally associated with the event. AF-related strokes are more severe than
strokes of other etiologies. In this context, we aimed to compare stroke severity
between ESUS patients diagnosed with AF during follow-up and those who were not.
We hypothesized that, if AF episodes detected during follow-up are indeed
causally associated with the index event, stroke severity in the AF group should
be higher than the non-AF group. METHODS: Dataset was derived from the Athens
Stroke Registry. ESUS was defined by the Cryptogenic Stroke/ESUS International
Working-Group criteria. Stroke severity was assessed by the National Institutes
of Health Stroke Scale (NIHSS) score. Cumulative probabilities of recurrent
stroke or peripheral embolism in the AF and non-AF ESUS groups were estimated by
Kaplan-Meier analyses. RESULTS: Among 275 ESUS patients, AF was detected during
follow-up in 80 (29.1%), either during repeated electrocardiogram monitoring
(18.2%) or during hospitalization for stroke recurrence (10.9%). NIHSS score was
similar between the two groups (5 [2-13] versus 5 [2-14], P = .998). More
recurrent strokes or peripheral embolisms occurred in the AF group compared with
the non-AF group (42.5% versus 13.3%, P = .001). CONCLUSIONS: Stroke severity is
similar between ESUS patients who were diagnosed with AF during follow-up and
those who were not. Given that AF-related strokes are more severe than strokes of
other etiologies, this finding challenges the assumption that the association
between ESUS and AF detected during follow-up is as frequently causal as
regarded.
PMID- 27612626
TI - Early Mobilization after Stroke: Changes in Clinical Opinion Despite an
Unchanging Evidence Base.
AB - BACKGROUND: We sought to determine whether Australasian health professionals'
opinions regarding early mobilization after stroke changed between 2008 and 2014,
when a large international trial of early mobilization (A Very Early
Rehabilitation Trial, AVERT) was underway. METHODS: Attendees at the two major
Australasian stroke conferences in 2008 and 2014 were surveyed. Participants
rated their agreement with statements about the risks and benefits of commencing
mobilization within 24 hours of hemorrhagic and ischemic stroke using a 5-point
Likert scale. Participants in 2014 were asked about their awareness of AVERT.
Logistic regressions were performed to determine whether the time point (2008
versus 2014) or awareness of AVERT influenced opinions about early mobilization.
RESULTS: Surveys were completed by 443 health professionals (2008: N = 202; 2014:
N = 241). Most respondents in 2014 reported that early mobilization was
beneficial and not harmful to people with ischemic and hemorrhagic stroke.
Opinions regarding mobilization after ischemic stroke did not change
significantly between 2008 and 2014. In 2014, a significantly greater proportion
of respondents believed that early mobilization after hemorrhagic stroke was
helpful (2008: n = 98 of 202 [49%] versus 2014: n = 170 of 241 [71%], P < .01).
Awareness of AVERT was significantly associated with the opinion that early
mobilization was beneficial and not harmful to patients with stroke (P < .05).
CONCLUSIONS: Australasian health professionals' opinions of early mobilization
after hemorrhagic stroke changed between 2008 and 2014, prior to reporting of the
AVERT trial. Our results suggest that awareness of an ongoing research trial can
lead to changes in opinions before the efficacy of the experimental intervention
is known.
PMID- 27612627
TI - Single-Phase Versus Multiphase CT Angiography in Middle Cerebral Artery Clot
Detection-Benefits for Less Experienced Radiologists and Neurologists.
AB - OBJECTIVES: CT angiography (CTA) is recommended as a standard of stroke imaging.
We investigated accuracy and precision of standard or single-phase CTA as
compared with novel technique or multiphase CTA in clot detection in the middle
cerebral artery. METHODS: Twenty single-phase CTA and twenty multiphase CTA with
prevailing M2 occlusion were assessed by 10 radiologists and 10 neurologists
blinded to clinical information (7 less experienced and 3 experienced).
Sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) were calculated as compared with reading by two seniors.
Reliability was calculated using Krippendorff's alpha (K-alpha). RESULTS:
Sensitivity, specificity, PPV, and NPV of single-phase CTA compared with
multiphase CTA for M2 clot presence were, respectively, .86, .75, .90, and .67
versus .88, .82, .92, and .72. For secondary or distal clots, sensitivity,
specificity, PPV, and NPV of single-phase CTA compared with multiphase CTA were
.41, .83, .50, and .78 versus .65, .77, .71, and .67. Agreement increased
significantly in favor of multiphase CTA for detection of primary clots from
moderate (.43) to substantial (.65) in less experienced radiologists and from
slight (.10) to moderate (.30) in less experienced neurologists. Agreement
significantly increased for distal or secondary clot detection in favor of
multiphase CTA from fair (.24) to moderate (.49) in experienced radiologists and
from slight (.12) to moderate (.46) in experienced neurologists. CONCLUSIONS:
Multiphase CTA is a reliable imaging tool in M2 clot detection and might
represent a beneficial imaging tool in clot detection for less experienced
physicians.
PMID- 27612628
TI - PARP-1 inhibition alleviates diabetic cardiac complications in experimental
animals.
AB - Cardiovascular complications are the major causes of mortality among diabetic
population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by
oxidative stress leading to cellular damage. We investigated the implication of
PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by
high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4
aminobenzamide (4-AB) was administered daily for ten weeks after diabetes
induction. At the end of study, surface ECG, blood pressure and vascular
reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite
contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin,
and tumor necrosis factor alpha (TNF-alpha) levels were measured in serum.
Finally, histological examination and collagen deposition detection in rat
ventricular and aortic sections were carried out. Hearts isolated from diabetic
animals showed increased PARP-1 enzyme activity compared to control animals while
significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB
alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP
1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced
by histopathological changes. In addition, 4-AB administration improved the
elevated blood pressure and the associated exaggerated vascular contractility,
endothelial destruction and vascular inflammation seen in diabetic animals.
Moreover, PARP-1 inhibition decreased serum levels of TNF-alpha and cardiac
nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1
inhibition did not significantly affect the developed hyperglycemia. Our findings
prove that PARP-1 enzyme plays an important role in diabetic cardiac
complications through combining inflammation, oxidative stress, and fibrosis
mechanisms.
PMID- 27612629
TI - Effects of P-glycoprotein on the intestine and blood-brain barrier transport of
YZG-331, a promising sedative-hypnotic compound.
AB - YZG-331 is a synthetic adenosine analogue which exhibits the sedative and
hypnotic effects by binding to the adenosine receptor. The present study was
designed to investigate the effects of P-glycoprotein (P-gp) on the intestine and
brain distribution of YZG-331 in vitro and in vivo as well as related binding
mechanisms. The activity of P-gp ATPase was both induced by YZG-331 and
verapamil, a typical P-gp inhibitor, but affinity of YZG-331 for P-gp was lower
than that of verapamil. The docking analyses further elucidated the binding
relationship of YZG-331 and P-gp. The directional transport of YZG-331 was
disappeared in Caco-2 and MDCK-MDR1 cells when the P-gp activity was blocked.
However, the penetration of digoxin, a P-gp known substrate, was not change in
MDCK-MDR1 cells along with YZG-331. In the everted intestinal sac model, the
influx of YZG-331 was significantly reduced in the presence of verapamil in all
the segments except for the colon. In the in situ and in vivo study, the brain
exposure of YZG-331 was promoted after co-administered of verapamil. Furthermore,
the Kp value changed from 0.03 to 0.05 after drug combination. Taken together,
these results indicated that YZG-331 is a substrate but may not an inhibitor of P
gp. The intestine and brain permeability of YZG-331 can be restricted, at least
in part, by P-gp. The drug interactions should be awarded when YZG-331 and other
P-gp-related drugs used together.
PMID- 27612630
TI - Theanine from tea and its semi-synthetic derivative TBrC suppress human cervical
cancer growth and migration by inhibiting EGFR/Met-Akt/NF-kappaB signaling.
AB - Cervical cancer is the third most prevalent cancer among women worldwide.
Theanine from tea and its derivatives show some anticancer activities. However,
the role of theanine and its derivatives against human cervical cancer and the
molecular mechanisms of action remain unclear. Thus, in this study, we aim to
investigate the anticancer activities and underlying mechanisms of theanine and a
theanine derivative, ethyl 6-bromocoumarin-3- carboxylyl L-theanine (TBrC),
against human cervical cancer. In vitro and in vivo assays for cancer cell growth
and migration have confirmed the inhibition of the cell growth and migration by
TBrC and theanine in highly-metastatic human cervical cancer. TBrC displays much
stronger activity than theanine on inhibition of the cell growth and migration as
well as induction of apoptosis and regulation of related protein expressions in
the human cervical cancer cells. TBrC and theanine greatly reduced endogenous and
exogenous factors-stimulated cell migration and completely repressed HGF- and
EGF+HGF-activated EGFR/Met-Akt/NF-kappaB signaling by reducing the
phosphorylation and expressions of EGFR, Met, Akt, and NF-kappaB in cervical
cancer cells. The enhancer of zeste homolog 2 (EZH2) knockdown decreased the
cancer cell migration and NF-kappaB expression. The NF-kappaB knockdown reduced
the cancer cell migration. TBrC and theanine reduced the EZH2 expression by more
than 80%. In addition, TBrC and theanine significantly suppressed human cervical
tumor growth in tumor-bearing nude mice without toxicity to the mice. Our results
suggest that TBrC and theanine may have the potentials of the therapeutic and/or
adjuvant therapeutic application in the treatment of human cervical cancer.
PMID- 27612631
TI - Acute appendicitis in children: not only surgical treatment.
AB - PURPOSE: An accurate diagnosis of acute appendicitis is important to avoid severe
outcome or unnecessary surgery but management is controversial. The aim of study
was to evaluate, in younger and older children, the efficacy of conservative
management for uncomplicated appendicitis and the outcome of complicated forms
underwent early surgery. METHODS: Children with acute appendicitis were
investigated by clinical, laboratory variables and abdominal ultrasound and
divided in two groups: complicated and uncomplicated. Complicated appendicitis
underwent early surgery; uncomplicated appendicitis started conservative
treatment with antibiotic. If in the next 24-48h it was worsening, the
conservative approach failed and patients underwent late surgery. RESULTS: A
total of 362 pediatric patients were included. One hundred sixty-five underwent
early appendectomy; 197 patients were at first treated conservatively: of these,
82 were operated within 24-48h for failure. The total percentage of operated
patients was 68.2%. An elevated association was found between surgery and
ultrasound. CONCLUSIONS: Conservative treatment for uncomplicated appendicitis
had high percentage of success (58%). Complications in operated patients were
infrequent. Our protocol was effective in order to decide which patients treat
early surgically and which conservatively; specific red flags (age and onset) can
identified patients at most risk of complications or conservative failure. TYPE
OF STUDY: treatment study. LEVEL OF EVIDENCE: II.
PMID- 27612632
TI - Gamifying Self-Management of Chronic Illnesses: A Mixed-Methods Study.
AB - BACKGROUND: Self-management of chronic illnesses is an ongoing issue in health
care research. Gamification is a concept that arose in the field of computer
science and has been borrowed by many other disciplines. It is perceived by many
that gamification can improve the self-management experience of people with
chronic illnesses. This paper discusses the validation of a framework (called The
Wheel of Sukr) that was introduced to achieve this goal. OBJECTIVE: This research
aims to (1) discuss a gamification framework targeting the self-management of
chronic illnesses and (2) validate the framework by diabetic patients, medical
professionals, and game experts. METHODS: A mixed-method approach was used to
validate the framework. Expert interviews (N=8) were conducted in order to
validate the themes of the framework. Additionally, diabetic participants
completed a questionnaire (N=42) in order to measure their attitudes toward the
themes of the framework. RESULTS: The results provide a validation of the
framework. This indicates that gamification might improve the self-management of
chronic illnesses, such as diabetes. Namely, the eight themes in the Wheel of
Sukr (fun, esteem, socializing, self-management, self-representation, motivation,
growth, sustainability) were perceived positively by 71% (30/42) of the
participants with P value <.001. CONCLUSIONS: In this research, both the
interviews and the questionnaire yielded positive results that validate the
framework (The Wheel of Sukr). Generally, this study indicates an overall
acceptance of the notion of gamification in the self-management of diabetes.
PMID- 27612633
TI - Moniliformediquinone as a potential therapeutic agent, inactivation of hepatic
stellate cell and inhibition of liver fibrosis in vivo.
AB - BACKGROUND: Moniliformediquinone (MFD), a phenanthradiquinone in Dendrobium
moniliforme, was synthesized in our laboratory. Beyond its in vitro inhibitory
effects on cancer cells, other biological activity of MFD is unknown. The purpose
of the present study was to investigate the effects of MFD on hepatic
fibrogenesis in vitro and in vivo. METHODS: Hepatic stellate HSC-T6 was cultured.
Cell viability assay and western blot analyses were performed. Male ICR mice were
evaluated on CCl4-induced hepatotoxicity using both histological examination and
immunohistochemical staining. RESULTS: First, in vitro study showed that the
synthesized MFD effectively attenuated the expression of transforming growth
factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), alpha-smooth
muscle actin (alpha-SMA), and type I collagen (COL-1), which modulated the
hepatic fibrogenesis. Furthermore, MFD reduced the phosphorylation of p65
NFkappaB in HSC-T6 cells. In vivo, liver fibrosis was induced by CCl4 twice a
week for 10 weeks in mice. The administration of the MFD was started after 1 week
of CCl4 thrice-weekly; the MFD significantly reduced plasma aspartate
transaminase (AST) and lactose dehydrogenase (LDH) as well as hepatic hydroxy
proline, alpha-SMA, and COL-1 expression in CCl4-treated mice. Pathological
analysis showed that the MFD alleviated CCl4-induced hepatic inflammation,
necrosis and fibrosis. These results suggest that MFD possesses therapeutic
potential for liver fibrosis. CONCLUSIONS: The synthesized MFD exhibits anti
fibrotic potential by inactivation of HSCs in vitro and decreases mouse hepatic
fibrosis in vivo. Further investigation into their clinical therapeutic potential
is required.
PMID- 27612634
TI - Trialling of an optimal health programme (OHP) across chronic disease.
AB - Population ageing is a worldwide phenomenon, most advanced in developed countries
and expected to continue over the next few decades. As people are surviving
longer with age-associated disease and disability, there is an imperative to
identify innovative solutions for an already overburdened health care system.
Such innovations need to be focused on disease management, taking into
consideration the strong associations that have been established between
psychosocial factors and pathophysiological mechanisms associated with chronic
disease. Aside from personal and community costs, chronic diseases produce a
significant economic burden due to the culmination of health care costs and lost
productivity. This commentary reports on a programme of research, Translating
Research, Integrated Public Health Outcomes and Delivery, which will evaluate an
optimal health programme that adopts a person-centred approach and engages
collaborative therapy to educate, support and improve the psychosocial health of
those with chronic disease. The effectiveness of the optimal health programme
will be evaluated across three of the most significant contributors to disease
burden: diabetes mellitus, chronic kidney disease and stroke. Cost-effectiveness
will also be evaluated. The findings derived from this series of randomised
controlled trials will also provide evidence attesting to the potential
applicability of the optimal health programme in other chronic conditions.
PMID- 27612635
TI - A robust data scaling algorithm to improve classification accuracies in
biomedical data.
AB - BACKGROUND: Machine learning models have been adapted in biomedical research and
practice for knowledge discovery and decision support. While mainstream
biomedical informatics research focuses on developing more accurate models, the
importance of data preprocessing draws less attention. We propose the Generalized
Logistic (GL) algorithm that scales data uniformly to an appropriate interval by
learning a generalized logistic function to fit the empirical cumulative
distribution function of the data. The GL algorithm is simple yet effective; it
is intrinsically robust to outliers, so it is particularly suitable for
diagnostic/classification models in clinical/medical applications where the
number of samples is usually small; it scales the data in a nonlinear fashion,
which leads to potential improvement in accuracy. RESULTS: To evaluate the
effectiveness of the proposed algorithm, we conducted experiments on 16 binary
classification tasks with different variable types and cover a wide range of
applications. The resultant performance in terms of area under the receiver
operation characteristic curve (AUROC) and percentage of correct classification
showed that models learned using data scaled by the GL algorithm outperform the
ones using data scaled by the Min-max and the Z-score algorithm, which are the
most commonly used data scaling algorithms. CONCLUSION: The proposed GL algorithm
is simple and effective. It is robust to outliers, so no additional denoising or
outlier detection step is needed in data preprocessing. Empirical results also
show models learned from data scaled by the GL algorithm have higher accuracy
compared to the commonly used data scaling algorithms.
PMID- 27612637
TI - The association between quitting smoking and weight gain: a systemic review and
meta-analysis of prospective cohort studies.
PMID- 27612638
TI - The future of guidelines: Primary care focused, patient oriented, evidence based
and simplified.
PMID- 27612636
TI - Effects of matrix metalloproteinases on the fate of mesenchymal stem cells.
AB - Mesenchymal stem cells (MSCs) have great potential as a source of cells for cell
based therapy because of their ability for self-renewal and differentiation into
functional cells. Moreover, matrix metalloproteinases (MMPs) have a critical role
in the differentiation of MSCs into different lineages. MSCs also interact with
exogenous MMPs at their surface, and regulate the pericellular localization of
MMP activities. The fate of MSCs is regulated by specific MMPs associated with a
key cell lineage. Recent reports suggest the integration of MMPs in the
differentiation, angiogenesis, proliferation, and migration of MSCs. These
interactions are not fully understood and warrant further investigation,
especially for their application as therapeutic tools to treat different
diseases. Therefore, overexpression of a single MMP or tissue-specific inhibitor
of metalloproteinase in MSCs may promote transdifferentiation into a specific
cell lineage, which can be used for the treatment of some diseases. In this
review, we critically discuss the identification of various MMPs and the
signaling pathways that affect the differentiation, migration, angiogenesis, and
proliferation of MSCs.
PMID- 27612639
TI - Burden of pneumocystis pneumonia in HIV-infected adults in sub-Saharan Africa: a
systematic review and meta-analysis.
AB - BACKGROUND: Seroprevalence data and clinical studies in children suggest that the
burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We
performed a systematic review to determine the prevalence and attributable
mortality of PCP amongst HIV-infected adults in sub-Saharan Africa. METHODS: We
searched Pubmed, Web of Science, Africa-Wide: NiPAD and CINAHL, from Jan 1 1995
to June 1 2015, for studies that reported the prevalence, mortality or case
fatality of PCP in HIV-infected adults living in sub-Saharan African countries.
Prevalence data from individual studies were combined by random-effects meta
analysis according to the Mantel-Haenszel method. Data were stratified by
clinical setting, diagnostic method, and study year. RESULTS: We included 48
unique study populations comprising 6884 individuals from 18 countries in sub
Saharan Africa. The pooled prevalence of PCP among 6018 patients from all
clinical settings was 15 . 4 % (95 % CI 12 . 9-18 . 0), and was highest amongst
inpatients, 22 . 4 % (95 % CI 17 . 2-27 . 7). More cases were identified by
bronchoalveolar lavage, 21 . 0 % (15 . 0-27 . 0), compared with expectorated, 7 .
7 % (4 . 4-11 . 1), or induced sputum, 11 . 7 % (4 . 9-18 . 4). Polymerase chain
reaction (PCR) was used in 14 studies (n = 1686). There was a trend of decreasing
PCP prevalence amongst inpatients over time, from 28 % (21-34) in the 1990s to 9
% (8-10) after 2005. The case fatality rate was 18 . 8 % (11 . 0-26 . 5), and PCP
accounted for 6 . 5 % (3 . 7-9 . 3) of study deaths. CONCLUSIONS: PCP is an
important opportunistic infection amongst HIV-infected adults in sub-Saharan
Africa, particularly amongst patients admitted to hospital. Although prevalence
appears to be decreasing, improved access to antiretroviral therapy and non
invasive diagnostics, such as PCR, are needed.
PMID- 27612640
TI - Concise Review: Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: A
Horse in the Race?
AB - Embryonic stem cells (ESC) hold promise for the treatment of human medical
conditions but are allogeneic. Here, we consider the differences between
autologous pluripotent stem cells produced by nuclear transfer (NT-ESCs) and
transcription factor-mediated, induced pluripotent stem cells (iPSCs) that impact
the desirability of each of these cell types for clinical use. The derivation of
NT-ESCs is more cumbersome and requires donor oocytes; however, the use of oocyte
cytoplasm as the source of reprogramming factors is linked to a key advantage of
NT-ESCs-the ability to replace mutant mitochondrial DNA in a patient cell (due to
either age or inherited disease) with healthy donor mitochondria from an oocyte.
Moreover, in epigenomic and transcriptomic comparisons between isogenic iPSCs and
NT-ESCs, the latter produced cells that more closely resemble bona fide ESCs
derived from fertilized embryos. Thus, although NT-ESCs are more difficult to
generate than iPSCs, the ability of somatic cell nuclear transfer to replace aged
or diseased mitochondria and the closer epigenomic and transcriptomic similarity
between NT-ESCs and bona fide ESCs may make NT-ESCs superior for future
applications in regenerative medicine. Stem Cells 2017;35:26-34.
PMID- 27612642
TI - Optimization of polyhydroxybutyrate production utilizing waste water as nutrient
source by Botryococcus braunii Kutz using response surface methodology.
AB - Investigations have been made to optimize various factors including pH,
temperature, and substrate for enhanced polyhydroxybutyrate (PHB) production in
Botryococcus braunii which serves as a pioneer for production of bioplastic
(PHB). Polyhydroxybutyrate is a natural, decomposable polymers accumulated by the
microorganism under different nutritional condition. Strain selection was done by
staining method using Sudan black and Nile red dye. Using response surface
methodology (RSM), three level- three variables Box Behnken design (BBD), the
best potential combination of pH (4-11), temperature (30-50 degrees C) and sewage
waste water as substrate fed at different concentrations at 20%-100% for maximum
PHB production was investigated. Maximum yield (247+/-0.42mg/L) of PHB dry weight
was achieved from the 60% concentration of sewage waste water as a growth medium
at pH 7.5 at 40 degrees C. It was well in close agreement with the value
predicted by RSM model yield (246+/- 0.32mg/L). Thus the study shows the
production of PHB by B. braunii along with the basic characterization of PHB by
using FTIR and TEM analysis. These preliminary studies indicated that PHB can
also be produced by B. braunii utilizing waste water. There is no report on the
optimization of PHB production in this microalgae have been documented.
PMID- 27612641
TI - Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop
in the Intestine and Transform into Lymphomas in Celiac Disease.
AB - The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors
remains controversial. Herein we showed that, in humans and in mice, innate
intestinal IELs expressing intracellular CD3 (iCD3(+)) differentiate along an Id2
transcription factor (TF)-independent pathway in response to TF NOTCH1,
interleukin-15 (IL-15), and Granzyme B signals. In NOTCH1-activated human
hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a
peptide lacking transcriptional activity. As a result, NOTCH1 target genes
indispensable for T cell differentiation were silenced and precursors were
reprogrammed into innate cells with T cell marks including intracellular CD3 and
T cell rearrangements. In the intraepithelial lymphoma complicating celiac
disease, iCD3(+) innate IELs acquired gain-of-function mutations in Janus kinase
1 or Signal transducer and activator of transcription 3, which enhanced their
response to IL-15. Overall we characterized gut T cell-like innate IELs,
deciphered their pathway of differentiation and showed their malignant
transformation in celiac disease.
PMID- 27612643
TI - Core-shell hyperbranched chitosan nanostructure as a novel electrode modifier.
AB - The present study reports, for the first time, the development and use of core
shell amino-terminated chitosan (Cs) hyperbranched nanoparticles (HBCs-NH2 NPs)
as a novel natural polymer-based electrode modifier for efficient electrochemical
systems. The electrochemical activity of the developed HBCs-NH2 NPs as compared
to Cs NPs was identified by standard oxidation-reduction reactions of
ferricyanide. The oxidation-reduction peaks height was about twofold higher than
the response of Cs-modified electrode. On the other hand, NADH oxidation at the
nanostructured surfaces confirmed the electrocatalytic activity where the
oxidation of NADH appeared at a lower overpotential (from 805mV to 635mV vs
Ag/AgCl). Eventually, a diffusion-controlled process was confirmed from the scan
rate effect.
PMID- 27612644
TI - Removal of nitrate and phosphate using chitosan/Al2O3/Fe3O4 composite nanofibrous
adsorbent: Comparison with chitosan/Al2O3/Fe3O4 beads.
AB - In the present study the chitosan/Al2O3/Fe3O4 composite nanofibrous adsorbent was
prepared by electrospinning process and its application for the removal of
nitrate and phosphate were compared with chitosan/Al2O3/Fe3O4 composite bead
adsorbent. The influence of Al2O3/Fe3O4 composite content, pH, contact time,
nitrate and phosphate initial concentrations and temperature on the nitrate and
phosphate sorption using synthesized bead and nanofibrous adsorbents was
investigated in a single system. The reusability of chitosan/Al2O3/Fe3O4
composite beads and nanofibers after five sorption-desorption cycles were carried
out. The Box-Behnken design was used to investigate the interaction effects of
adsorbent dosage, nitrate and phosphate initial concentrations on the nitrate and
phosphate removal efficiency. The pseudo-second-order kinetic model and known
Freundlich and Langmuir isotherm models were used to describe the kinetic and
equilibrium data of nitrate and phosphate sorption using chitosan/Al2O3/Fe3O4
composite beads and nanofibers. The influence of other anions including chloride,
fluoride and sulphate on the sorption efficiency of nitrate and phosphate was
examined. The obtained results revealed the higher potential of
chitosan/Al2O3/Fe3O4 composite nanofibers for nitrate and phosphate compared with
chitosan/Al2O3/Fe3O4 composite beads.
PMID- 27612645
TI - Structural properities and immunoenhancement of an exopolysaccharide produced by
Phellinus pini.
AB - Phellinus pini exopolysaccharide (PPE) is a mannan produced by P. pini when
cultured in potato dextroseagar medium. Partial hydrolysis with acid, periodate
oxidation and Smith degradation, methylation and 13C nuclear magnetic resonance
(NMR) spectroscopy were used to elaborate its structure. Results indicated that
PPE contained a backbone of (1->2)-linked Man, which was heavily substituted via
(1->6)-glucosidic bonds with (1->3)-linked Man, and terminated mainly with Man,
as well as a small amount of Gal and Glc. Immunological tests showed that PPE
exhibited high macrophages-activating ability, thereby augmenting phagocytosis
and enhancing the production of nitric oxide, tumour necrosis factor-alpha and
reactive oxygen species. Therefor, PPE had potential applications in developing
functional food or in serving as a natural immnunostimulant.
PMID- 27612646
TI - Noise contributions to the fMRI signal: An overview.
AB - The ability to discriminate signal from noise plays a key role in the analysis
and interpretation of functional magnetic resonance imaging (fMRI) measures of
brain activity. Over the past two decades, a number of major sources of noise
have been identified, including system-related instabilities, subject motion, and
physiological fluctuations. This article reviews the characteristics of the
various noise sources as well as the mechanisms through which they affect the
fMRI signal. Approaches for distinguishing signal from noise and the associated
challenges are also reviewed. These challenges reflect the fact that some noise
sources, such as respiratory activity, are generated by the same underlying brain
networks that give rise to functional signals that are of interest.
PMID- 27612647
TI - Fast and sequence-adaptive whole-brain segmentation using parametric Bayesian
modeling.
AB - Quantitative analysis of magnetic resonance imaging (MRI) scans of the brain
requires accurate automated segmentation of anatomical structures. A desirable
feature for such segmentation methods is to be robust against changes in
acquisition platform and imaging protocol. In this paper we validate the
performance of a segmentation algorithm designed to meet these requirements,
building upon generative parametric models previously used in tissue
classification. The method is tested on four different datasets acquired with
different scanners, field strengths and pulse sequences, demonstrating comparable
accuracy to state-of-the-art methods on T1-weighted scans while being one to two
orders of magnitude faster. The proposed algorithm is also shown to be robust
against small training datasets, and readily handles images with different MRI
contrast as well as multi-contrast data.
PMID- 27612648
TI - Controlled formaldehyde fixation of fibronectin layers for expansion of
mesenchymal stem cells.
AB - Extracellular cell matrices deposited by cells stimulate cell proliferation.
However, their generation is cumbersome and time consuming. We show here that
controlled fixation of fibronectin layers after coating culture vessels
significantly enhances expansion of murine and human mesenchymal stem cells
(MSCs) and, to a lesser extent, primary fibroblasts. In contrast, fibronection
fixation did not stimulate proliferation of established cancer cell lines. Fixed
vitronectin or collagen IV layers also enhanced proliferation of murine MSCs.
Thus, controlled formaldehyde fixation of layers formed by fibronectin or some
other extracellular matrix components represents a simple and reproducible way to
enhance proliferation of primary cells.
PMID- 27612649
TI - A colorimetric detection method of pesticide acetamiprid by fine-tuning aptamer
length.
AB - This work investigates the effect of shortening aptamer sequences on the
colorimetric detection of acetamiprid using aptamer-wrapped gold nanoparticles
(AuNPs). Truncated 37-mer and 25-mer aptamers were generated by deleting excess
flanking nucleotides from parental 49-mer acetamiprid-target aptamer. In
comparing the responses of the three sequences, truncated aptamers did not
improve the ability to discriminate against other tested pesticides. However,
comparison between 49-mer and other shorter aptamers showed that shortening
aptamer sequences through removing excess flanking nucleotides outsides of
binding region improved colorimetric sensitivity for acetamiprid by 3.3 fold. Due
to excess bases, the target-bound aptamer might still adhere to AuNPs, resulting
in incomplete dissociation of aptamer from AuNPs and therefore the suppression of
aggregation responses. This work provides further insight to the effects of
aptamer structure on detection of the target, as well as a method by fine-tuning
aptamer length for rapid detection of pesticide residues in environments or food.
PMID- 27612650
TI - Editors' Note: Chirality in Separation Science and Molecular Recognition Honoring
Prof. F. Gasparrini Thematic Issue 2016.
PMID- 27612652
TI - Protist Collections: Essential for Future Research.
AB - The vouchered deposit of protist type specimens in institution-maintained
collections is a prerequisite for species description, and greatly enhances the
chances of sample availability and preservation for future generations. However,
specimens are currently most often deposited in personal collections maintained
by the individual effort of researchers. We discuss the disadvantages of such a
scenario and propose a change to this arrangement.
PMID- 27612651
TI - Putting Infection Dynamics at the Heart of Chagas Disease.
AB - In chronic Trypanosoma cruzi infections, parasite burden is controlled by
effective, but nonsterilising immune responses. Infected cells are difficult to
detect because they are scarce and focally distributed in multiple sites.
However, advances in detection technologies have established a link between
parasite persistence and the pathogenesis of Chagas heart disease. Long-term
persistence likely involves episodic reinvasion as well as continuous infection,
to an extent that varies between tissues. The primary reservoir sites in humans
are not definitively known, but analysis of murine models has identified the
gastrointestinal tract. Here, we highlight that quantitative, spatial, and
temporal aspects of T. cruzi infection are central to a fuller understanding of
the association between persistence, pathogenesis, and immunity, and for
optimising treatment.
PMID- 27612653
TI - Probiotic administration among free-living older adults: a double blinded,
randomized, placebo-controlled clinical trial.
AB - BACKGROUND: Diseases of the digestive system have been found to contribute to a
higher symptom burden in older adults. Thus, therapeutic strategies able to treat
gastrointestinal discomfort might impact the overall health status and help older
adults to increase their overall health status and optimal functionality.
OBJECTIVE: The aim of this double-blinded, randomized, placebo-controlled
clinical trial was to evaluate the effect of the probiotic strain Lactobacillus
reuteri on digestive health and wellbeing in older adults. METHODS: The study
enrolled general older adults (>65 years). After eligibility screening qualified
subjects (n = 290) participated in a 2-arm study design, with each arm consisting
of 12 weeks of intervention of either active or placebo product. Primary outcome
measure was set to changes in gastrointestinal symptoms and secondary outcome
measures were changes in level of wellbeing, anxiety and stress. Follow up was
performed at 8 and 12 weeks. RESULTS: No persistent significant effects were
observed on the primary or secondary outcome parameters of the study. A modest
effect was observed in the probiotic arm, were levels of stress decreased at week
8 and 12. Similarly, we found that subjects suffering from indigestion and
abdominal pain, respectively, showed a significant decrease of anxiety at week 8
after probiotic treatment, but not at week 12. CONCLUSION: The RCT failed to show
any improvement in digestive health after daily intake of a probiotic supplement
containing L. reuteri. Neither was any significant improvement in wellbeing,
stress or anxiety observed. Even though the RCT had a negative outcome, the study
highlights issues important to take into consideration when designing trials
among older adults. TRIAL REGISTRATION: Clinicaltrials.gov/ NCT01837940 .
PMID- 27612654
TI - In vitro effects of photodynamic therapy induced by chloroaluminum phthalocyanine
nanoemulsion.
AB - BACKGROUND: The photodynamic therapy (PDT) has been used to treat cancer mainly
by inducing oxidative stress. Our aim was to evaluate the effect of PDT and its
combination with methoxyamine (MX), a blocker of base excision repair (BER), in
cells expressing high levels of the APE1 protein, which is involved in cell
oxidative damage response. METHODS: The HeLa and A549 cells were treated for 3h
with chloroaluminum phthalocyanine incorporated into a well-designed nanoemulsion
(ClAlPc/NE); and then irradiated by visible light (@670nm) with doses of 0.1, 0.5
and 1.0J/cm2. A simultaneous combination of MX+ClAlPc/NE was performed and then
irradiated with the selected dose of 0.5J/cm2. The treatments were evaluated in
terms of viability, clonogenicity, DNA fragmentation, and cell death mechanism by
apoptosis and/or necrosis. RESULTS: The APE1 protein expression observed was
higher in HeLa than in A549. Both cell lines exhibited substantial differences in
cell cytotoxicity. The PDT decreased the clonogenicity of HeLa by inducing
apoptosis (sub-G1 and annexin detection). Additionaly, the MX potentiates the PDT
effects in HeLa. Otherwise, low cytotoxicity was observed in A549 cells.
CONCLUSION: The PDT induced apoptosis in high APE1 expressive HeLa cells, and the
blockage of BER by MX increased its effects.
PMID- 27612655
TI - How contexts promote and prevent relapse to drug seeking.
AB - The contexts where drugs are self-administered play an important role in
regulating persistent drug taking and in relapse to such taking after periods of
abstinence. Here, we review the behavioral and brain mechanisms enabling contexts
to promote and prevent relapse to drug seeking. We review the key brain
structures, their neuropharmacology and their connectivity. We discuss the
similarities and differences between the mechanisms for context-induced
reinstatement of drug seeking vs. other forms of relapse to drug seeking in
animal models and we highlight the numerous deficits in our understanding. We
emphasize that current understanding, although significant, defies explanations
in terms of models at the level of brain structures and their connectivity.
Rather, we show that there is significant functional compartmentalization and
segregation within these structures during reinstatement and extinction of drug
seeking that parallels their anatomical segregation into circuits and channels. A
key challenge is to recognize this complexity, understand how these circuits and
channels are organized, as well as understand how different modes of activity of
ensembles of neurons within them promote abstinence or relapse to drug seeking.
PMID- 27612656
TI - Systems biology integration of proteomic data in rodent models of depression
reveals involvement of the immune response and glutamatergic signaling.
AB - PURPOSE: The pathophysiological basis of major depression is incompletely
understood. Recently, numerous proteomic studies have been performed in rodent
models of depression to investigate the molecular underpinnings of depressive
like behaviours with an unbiased approach. The objective of the study is to
integrate the results of these proteomic studies in depression models to shed
light on the most relevant molecular pathways involved in the disease.
EXPERIMENTAL DESIGN: Network analysis is performed integrating preexisting
proteomic data from rodent models of depression. The IntAct mouse and the HRPD
are used as reference protein-protein interaction databases. The functionality
analyses of the networks are then performed by testing overrepresented GO
biological process terms and pathways. RESULTS: Functional enrichment analyses of
the networks revealed an association with molecular processes related to
depression in humans, such as those involved in the immune response. Pathways
impacted by clinically effective antidepressants are modulated, including
glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of
proteins regulating energy metabolism and circadian rhythms are implicated. The
comparison with protein pathways modulated in depressive patients revealed
significant overlapping. CONCLUSIONS AND CLINICAL RELEVANCE: This systems biology
study supports the notion that animal models can contribute to the research into
the biology and therapeutics of depression.
PMID- 27612659
TI - Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection
in Chinese Han population.
AB - OBJECTIVE: Studies have indicated that AMPK play critical roles in the regulation
of innate immunity and inflammatory responses. However, the role of the
polymorphisms of PRKAA1 gene in immune-response to infectious organisms remains
unknown. To evaluate the potential role of PRKAA1/AMPKalpha1 in the immune
response to HBV, we conducted this case-control study. METHODS: We recruited 276
patients (145 men and 131 women; average age, 51.6 years) with chronic HBV
infection (CHB) and 303 healthy controls (166 men and 137 women; average age,
54.2 years). All the subjects were unrelated individuals of Chinese Han
Population. Three SNPs of PRKAA1gene were tested. RESULTS: Rs1002424 polymorphism
showed significant difference in the allele frequencies, but no difference in the
genotype frequencies (allele: p=0.039411, OR95%CI=0.783479 [0.621067-0.988362];
genotype: p=0.104758); rs13361707 polymorphism showed significance in allele
analysis, but not in genotype analysis (allele: p=0.034749, OR95%CI=1.284303
[1.017958-1.620335]; genotype: p=0.098027); rs3792822 polymorphism was
demonstrated to have significant differences in both genotype and allele
frequencies between cases and controls (allele: p=0.029286, OR95%CI= 0.741519
[0.566439-0.970716]; genotype: p=0.034560). The haplotype results showed that CTG
and TCA in the rs13361707-rs1002424-rs3792822 block were significantly associated
with the happening of HBV (CTG: p=0.036854, OR95%CI=1.281 [1.015-1.617];
p=0.030841, OR95%CI=0.743 [0.568-0.973]). CONCLUSION: These findings suggest that
PRKAA1 polymorphisms may contribute to the susceptibility of chronic HBV
infection in Chinese Han origin.
PMID- 27612658
TI - Thyrotropin and CD40L Stimulate Interleukin-12 Expression in Fibrocytes:
Implications for Pathogenesis of Thyroid-Associated Ophthalmopathy.
AB - BACKGROUND: Increased numbers of bone marrow-derived progenitor cells, known as
fibrocytes, populate the peripheral circulation, orbit, and thyroid of patients
with Graves' disease (GD). These cells have been implicated in the development of
thyroid-associated ophthalmopathy. They can differentiate into myofibroblasts or
adipocytes, produce inflammatory cytokines, and remodel tissue. This study sought
to determine whether thyrotropin (TSH) and CD40 ligand (CD40L), implicated in the
pathogenesis of GD, induce interleukin-12 (IL-12) in human fibrocytes. MATERIALS
AND METHODS: IL-12 protein concentrations and mRNA levels were measured by
Luminex and real-time polymerase chain reaction, respectively. Flow cytometry
assessed intracellular IL-12 concentrations. Vector containing IL-12p40 promoter
was transfected into cultured fibrocytes, and promoter activity was monitored
using luciferase assay. RESULTS: TSH and CD40L stimulated intracellular IL-12
protein accumulation in peripheral blood fibrocytes. Inhibiting Akt and nuclear
factor-kappaB (NF-kappaB) activity diminished IL-12 expression in fibrocytes,
while TSH did not induce promoter activity. TSH-mediated IL-12 production
required de novo synthesized proteins and augmented IL-12 mRNA stability. IL-12
production mediated by CD40L required tumor necrosis factor receptor-associated
factor 6. CONCLUSION: TSH and CD40L induce IL-12 expression in fibrocytes, and
Akt and NF-kappaB mediate this activity. Given the importance of IL-12 in immune
function, its production by fibrocytes may promote an inflammatory immune
response and tissue remodeling in thyroid-associated ophthalmopathy.
PMID- 27612657
TI - Age-related alterations in immune responses to West Nile virus infection.
AB - West Nile virus (WNV) is the most important causative agent of viral encephalitis
worldwide and an important public health concern in the United States due to its
high prevalence, severe disease, and the absence of effective treatments.
Infection with WNV is mainly asymptomatic, but some individuals develop severe,
possibly fatal, neurological disease. Individual host factors play a role in
susceptibility to WNV infection, including genetic polymorphisms in key anti
viral immune genes, but age is the most well-defined risk factor for
susceptibility to severe disease. Ageing is associated with distinct changes in
immune cells and a decline in immune function leading to increased susceptibility
to infection and reduced responses to vaccination. WNV is detected by pathogen
recognition receptors including Toll-like receptors (TLRs), which show reduced
expression and function in ageing. Neutrophils, monocyte/macrophages and
dendritic cells, which first recognize and respond to infection, show age-related
impairment of many functions relevant to anti-viral responses. Natural killer
cells control many viral infections and show age-related changes in phenotype and
functional responses. A role for the regulatory receptors Mertk and Axl in blood
brain barrier permeability and in facilitating viral uptake through phospholipid
binding may be relevant for susceptibility to WNV, and age-related up-regulation
of Axl has been noted previously in human dendritic cells. Understanding the
specific immune parameters and mechanisms that influence susceptibility to
symptomatic WNV may lead to a better understanding of increased susceptibility in
elderly individuals and identify potential avenues for therapeutic approaches: an
especially relevant goal, as the world's populating is ageing.
PMID- 27612660
TI - Serum concentration of ketamine and antinociceptive effects of ketamine and
ketamine-lidocaine infusions in conscious dogs.
AB - BACKGROUND: Central sensitization is a potential severe consequence of invasive
surgical procedures. It results in postoperative and potentially chronic pain
enhancement. It results in postoperative pain enhancement; clinically manifested
as hyperalgesia and allodynia. N-methyl-D-aspartate (NMDA) receptor plays a
crucial role in the mechanism of central sensitisation. Ketamine is most commonly
used NMDA-antagonist in human and veterinary practice. However, the
antinociceptive serum concentration of ketamine is not yet properly established
in dogs. Six dogs were used in a crossover design, with one week washout period.
Treatments consisted of: 1) 0.5 mg/kg ketamine followed by continuous rate
infusion (CRI) of 30 MUg/kg/min; 2) 0.5 mg/kg ketamine followed by CRI of 30
MUg/kg/min and lidocaine (2 mg/kg followed by CRI of 100 MUg/kg/min); and 3) 0.5
mg/kg ketamine followed by CRI of 50 MUg/kg/min. The infusion was administered up
to 120 min. Nociceptive thresholds and ketamine serum concentrations were
measured before drug administration, and at 5, 10, 20, 40, 60, 90, 120, 140 and
160 min after the start of infusion. RESULTS: Maximum concentration recorded was
435.34 +/- 26.18 ng/mL, 582.34 +/- 227.46 ng/mL and 733.77 +/- 133.6 ng/mL for
K30, KL30 and K50, respectively. The concentration at 120 min was 250.87 +/-
39.87, 221.73 +/- 91.03 and 343.67 +/- 63.21 ng/mL at 120 min in K30, KL30 and
K50, respectively. All the three infusion regimes maintained serum concentrations
above 200 ng/mL. The thresholds returned towards baseline values within 20 min,
after cessation of infusion. CONCLUSION: Serum concentration to produce
mechanical antinociceptive effects in dogs is between 100 and 200 ng/mL. All the
three infusion regimes in this study provided antinociceptive effects throughout
the infusions. In this study, we found that the serum concentration of ketamine
to produce mechanical antinociceptive effects in dogs is above 200 ng/mL. All
three infusion regimes provided antinociceptive effects throughout the infusions
without causing harmful effects. Further studies are recommended in a clinical
setting.
PMID- 27612661
TI - Directed evolution of glutathione transferases towards a selective glutathione
binding site and improved oxidative stability.
AB - BACKGROUND: Glutathione transferases (GSTs) are a family of detoxification
enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic
compounds. METHODS: A library of alpha class GSTs was constructed by DNA
shuffling using the DNA encoding the human glutathione transferase A1-1 (hGSTA1
1) and the rat glutathione transferase A1-1 (rGSTA1-1). RESULTS: Activity
screening of the library allowed the selection of a chimeric enzyme variant
(GSTD4) that displayed high affinity towards GSH and GSH-Sepharose affinity
adsorbent, higher kcat/Km and improved thermal stability, compared to the parent
enzymes. The crystal structures of the GSTD4 enzyme in free form and in complex
with GSH were determined to 1.6A and 2.3A resolution, respectively. Analysis of
the GSTD4 structure showed subtle conformational changes in the GSH-binding site
and in electron-sharing network that may contribute to the increased GSH
affinity. The shuffled variant GSTD4 was further optimized for improved oxidative
stability employing site-saturation mutagenesis. The Cys112Ser mutation confers
optimal oxidative stability and kinetic properties in the GSTD4 enzyme.
CONCLUSIONS: DNA shuffling allowed the creation of a chimeric enzyme variant with
improved properties, compared to the parent enzymes. X-ray crystallography shed
light on how recombination of a specific segment from homologous GSTA1-1 together
with point mutations gives rise to a new functionally competent enzyme with
improved binding, catalytic properties and stability. GENERAL SIGNIFICANCE: Such
an engineered GST would be useful in biotechnology as affinity tool in affinity
chromatography as well as a biocatalytic matrix for the construction of biochips
or enzyme biosensors.
PMID- 27612662
TI - S-nitrosylation of peroxiredoxin 1 contributes to viability of lung epithelial
cells during Bacillus anthracis infection.
AB - BACKGROUND: Using Bacillus anthracis as a model gram-positive bacterium, we
investigated the effects of host protein S-nitrosylation during bacterial
infection. B. anthracis possesses a bacterial nitric oxide synthase (bNOS) that
is important for its virulence and survival. However, the role of S-nitrosylation
of host cell proteins during B. anthracis infection has not been determined.
METHODS: Nitrosoproteomic analysis of human small airway epithelial cells
(HSAECs) infected with toxigenic B. anthracis Sterne was performed, identifying
peroxiredoxin 1 (Prx1) as one predominant target. Peroxidase activity of Prx
during infection was measured using 2-Cys-Peroxiredoxin activity assay. Chaperone
activity of S-nitrosylated Prx1 was measured by insulin aggregation assay, and
analysis of formation of multimeric species using Native PAGE. Griess assay and
DAF-2DA fluorescence assay were used to measure NO production. Cell viability was
measured using the Alamar Blue assay and the ATPlite assay (Perkin Elmer).
RESULTS: S-nitrosylation of Prx1 in Sterne-infected HSAECs leads to a decrease in
its peroxidase activity while enhancing its chaperone function. Treatment with
bNOS inhibitor, or infection with bNOS deletion strain, reduces S-nitrosylation
of Prx1 and decreases host cell survival. Consistent with this, siRNA knockdown
of Prx1 lowers bNOS-dependent protection of HSAEC viability. CONCLUSIONS: Anthrax
infection results in S-nitrosylation of multiple host proteins, including Prx1.
The nitrosylation-dependent decrease in peroxidase activity of Prx1 and increase
in its chaperone activity is one factor contributing to enhancing infected cell
viability. GENERAL SIGNIFICANCE: These results provide a new venue of mechanistic
investigation for inhalational anthrax that could lead to novel and potentially
effective countermeasures.
PMID- 27612664
TI - Kaposi's sarcoma of the hard palate.
PMID- 27612663
TI - Toxicity evaluations of nanoclays and thermally degraded byproducts through
spectroscopical and microscopical approaches.
AB - BACKGROUND: Montmorillonite is a type of nanoclay that originates from the clay
fraction of the soil and is incorporated into polymers to form nanocomposites
with enhanced mechanical strength, barrier, and flammability properties used for
food packaging, automotive, and medical devices. However, with implementation in
such consumer applications, the interaction of montmorillonite-based composites
or derived byproducts with biological systems needs to be investigated. METHODS:
Herein we examined the potential of Cloisite Na+ (pristine) and Cloisite 30B
(organically modified montmorillonite nanoclay) and their thermally degraded
byproducts' to induce toxicity in model human lung epithelial cells. The
experimental set-up mimicked biological exposure in manufacturing and disposal
areas and employed cellular treatments with occupationally relevant doses of
nanoclays previously characterized using spectroscopical and microscopical
approaches. For nanoclay-cellular interactions and for cellular analyses
respectively, biosensorial-based analytical platforms were used, with induced
cellular changes being confirmed via live cell counts, viability assays, and cell
imaging. RESULTS: Our analysis of byproducts' chemical and physical properties
revealed both structural and functional changes. Real-time high throughput
analyses of exposed cellular systems confirmed that nanoclay induced significant
toxic effects, with Cloisite 30B showing time-dependent decreases in live cell
count and cellular viability relative to control and pristine nanoclay,
respectively. Byproducts produced less toxic effects; all treatments caused
alterations in the cell morphology upon exposure. CONCLUSIONS: Our morphological,
behavioral, and viability cellular changes show that nanoclays have the potential
to produce toxic effects when used both in manufacturing or disposal
environments. GENERAL SIGNIFICANCE: The reported toxicological mechanisms prove
the extensibility of a biosensorial-based platform for cellular behavior analysis
upon treatment with a variety of nanomaterials.
PMID- 27612665
TI - Oxidative stress of imidaclothiz on earthworm Eisenia fetida.
AB - Imidaclothiz, a kind of neonicotinoid insecticides, is developed as a commercial
pesticide in China and used for the control of sucking and biting insects,
including aphids, whiteflies, beetles and some Lepidoptera species as well. In
recent years, more and more attention has been focused on the adverse effects of
neonicotinoid insecticides on non-target organisms. In this study, inhibition
effects of imidaclothiz and recovery capacity of molecular biomarkers (GST, CE,
CAT, SOD and POD activity, and DNA damage) in earthworms were detected for the
first time. Earthworms were exposed to imidaclothiz (0.3 and 1.0mgkg-1) for
28days, and then transferred to the clean artificial soil for 28days. Regarding
enzyme activities, GST, CE, CAT and POD were inhibited following exposure to
imidaclothiz at one or more sample times, while SOD was not affected. After
transferring to the clean artificial soil, POD continued to be significantly
inhibited till sample time 35days at 0.3mg/kg-1. For GST, CE, CAT and SOD,
activities of them were significantly increased compared to those of the control
during the recovery period. The olive tail moments (OTM) in comet assay, as an
indication of DNA damage, were significantly increased compared to the control
after treatment and then decreased during the recovery period. These results
suggested that imidaclothiz induced oxidative damage on earthworms which caused
damage to vital macromolecules including DNA. However, the recovery changes of
all tested biomarkers following the transfer to clean soil suggested the tested
earthworm recovery from imidaclothiz exposure.
PMID- 27612667
TI - Developmental expression and regulation of flavin-containing monooxygenase by the
unfolded protein response in Japanese medaka (Oryzias latipes).
AB - Flavin-containing monooxygenases (FMOs) play a key role in xenobiotic metabolism,
are regulated by environmental conditions, and are differentially regulated
during mammalian development. Japanese medaka (Oryzias latipes) are a common
model organism for toxicological studies. The goal of the current research was to
characterize developmental expression and regulation of FMOs in Japanese medaka
embryos to better understand the role of FMOs in this model species. Five
putative medaka fmos were characterized from the medaka genome through the
National Center for Biotechnology Information (NCBI) database by protein motifs
and alignments, then identified as fmo4, fmo5A, fmo5B, fmo5C and fmo5D for the
current study. Fmo gene expression was analyzed at 1dpf, 3dpf, 6dpf and 9dpf and
distinct developmental patterns of expression were observed. Fmo4 and fmo5D
increased 3-fold during mid organogenesis (6dpf), while fmo5B and fmo5C decreased
significantly in early organogenesis (3dpf) and fmo5A was unaltered. Promoter
analysis was performed for transcription factor binding sites and indicated
regulation by developmental factors and a role for the unfolded protein response
in fmo modulation. Fmo regulation by the UPR was assessed with treatments of
1MUg/ml, 2MUg/ml, and 4MUg/ml Tunicamycin (Tm), and 2mM and 4mM dithiothreitol
(DTT), well-known inducers of endoplasmic reticulum stress, for 24h from 5-6dpf.
High concentrations to Tm induced fmo4 and fmo5A up to two-fold, while DTT
significantly decreased expression of fmo5A, fmo5B, and fmo5C. Results suggest
that medaka fmos are variably regulated by the UPR during organogenesis with
variable developmental expression, and suggesting potential stage-dependent
activation or detoxification of xenobiotics.
PMID- 27612666
TI - Extending the toxicity-testing paradigm for freshwater mussels: Assessing chronic
reproductive effects of the synthetic estrogen 17alpha-ethinylestradiol on the
unionid mussel Elliptio complanata.
AB - Surface water concentrations of the synthetic estrogen 17alpha-ethinylestradiol
(EE2) as low as 1ng/L can cause adverse reproductive effects in fish under acute
and chronic exposure conditions, whereas higher concentrations (> 5ng/L) in acute
studies are necessary to elicit adverse effects in freshwater mussels. Prolonged
chronic exposures of freshwater mussels to EE2 remain un-evaluated. An extended
duration testing paradigm was used to examine reproductive and biochemical
(carbohydrate, lipid, protein) effects of EE2 on the unionid mussel, Elliptio
complanata, throughout its reproductive cycle. Mussels were exposed to a control
and EE2 concentrations (5 and 50ng/L) in six discrete and sequential 28 d tests,
and in one discrete and simultaneous 180 d test, from February through August.
Foot protrusion and siphoning behavior were recorded daily, along with
conglutinate releases and larval (glochidia) mortality. Gonad, hemolymph, and
gonad fluid samples were taken for biochemical and vitellogenin-like protein
(Vtg) analysis post-exposure. Female mussels released eggs and conglutinates
during the months of April to June, indicating sexual maturation during this
time. Conglutinates released in the 5ng/L treatment in 28 d exposures contained
fewer glochidia and more eggs, and increased concentrations of Vtg in hemolymph
were observed from April to August in the 5ng/L treatment during the 180 d
exposure. Results indicate that the 180 d test approach, concurrent with the
sequence of 28 d tests, enabled a more robust evaluation of mussel behavior and
physiology than would have been possible with a single short-term (28 d) test.
PMID- 27612669
TI - Drinking, Drug Use, and Related Consequences Among University Students Completing
Study Abroad Experiences: A Systematic Review.
AB - BACKGROUND: University students who complete study abroad experiences are
potentially exposed to behaviors, in particular alcohol and drug use, that place
their health at risk. There is a need to identify risk and protective factors and
highlight knowledge gaps. METHODS: A systematic review adopting the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology.
Relevant bibliographic databases and online repositories were systematically
searched for both qualitative and quantitative peer-reviewed studies. RESULTS:
Eighteen articles were eligible for inclusion. Degree mobility students (DMSs
students pursuing a full bachelor or master degree in a foreign country) and
Credit Mobility Students (CMSs-students participating in short term or semester
study abroad programmes) show different patterns of at-risk behaviors compared to
pre-departure, and to domestic or non-study abroad students. DMSs mostly consumed
less alcohol and illicit substances compared to domestic students, but little
information on pre-travel behavior and predictors of at-risk behaviors while
abroad was available on DMSs. Most studies indicated that CMSs increased their
alcohol use while abroad and reduced it when they returned home. However, there
is no evidence of an increase in the negative consequences associated with
alcohol misuse while abroad. Different pre-departure and abroad factors (e.g.,
perceptions of peer drinking norms, psychological and sociocultural adjustment
abroad) were related to at-risk behaviors in the host country. CONCLUSIONS:
University students who study abroad are understudied and potentially at risk
from alcohol and drug use. Knowledge gaps are discussed in relation to possible
future qualitative, mixed methods and longitudinal research.
PMID- 27612668
TI - Effects of mutations in Wnt/beta-catenin, hedgehog, Notch and PI3K pathways on
GSK-3 activity-Diverse effects on cell growth, metabolism and cancer.
AB - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates
in an array of critical cellular processes. GSK-3 was first characterized as an
enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent
studies have revealed that this moon-lighting protein is involved in numerous
signaling pathways that regulate not only metabolism but also have roles in:
apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis,
migration, regulation of gene transcription, stem cell biology and survival. In
this review, we will discuss the roles that GSK-3 plays in various diseases as
well as how this pivotal kinase interacts with multiple signaling pathways such
as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and
TP53. Mutations that occur in these and other pathways can alter the effects that
natural GSK-3 activity has on regulating these signaling circuits that can lead
to cancer as well as other diseases. The novel roles that microRNAs play in
regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and
these other pathways may improve therapy and overcome therapeutic resistance.
PMID- 27612670
TI - Skeletal muscle imaging in neuromuscular disease.
AB - Skeletal muscle imaging is increasingly used as a complement to clinical and
electrophysiological examination in neuromuscular disease. Ultrasound and MRI
have developed as the modalities of choice, each with strengths and limitations.
Characteristic changes of muscle denervation and myopathy are seen on imaging
which may delineate the nature of the disease process or help guide muscle
biopsy. Identifying patterns of muscle involvement in hereditary myopathies may
inform genetic testing. This review discusses skeletal muscle imaging in
neuromuscular disease focusing on practical applications of current and emerging
ultrasound and MRI techniques.
PMID- 27612671
TI - Scoliosis surgery in the elderly: Complications, readmissions, reoperations and
mortality.
AB - The operative management of scoliosis in the elderly remains controversial. The
authors of this study sought to evaluate outcomes in elderly patients with
scoliosis undergoing deformity correction. Patient data was obtained from a 5%
sample of the Medicare Provided Analysis and Review database (MEDPAR). Patients
over 65years of age with scoliosis undergoing corrective surgery were identified
between the years 2005 to 2011. A total of 453 patients were analyzed: 262 (57%)
between ages 66 to 74years, and 191 (42%) over the age of 75years. Female
predominance (78%) was observed in this sample. Pre-diagnosis follow-up averaged
118months. Post-surgery follow-up averaged 33months. Patients between 66 and
74years old were mostly discharged home, while patients over the age of 75years
were discharged to skilled nursing facilities (SNFs) (38.55% versus 34.04%, p
value=0.0011). Readmission rates were lower in patients between 66 and 74years
old when compared to patients over the age of 75years (9.92% versus 17.28%, p
value=0.0217). Complication rates 30-days after discharge were less in patients
between 66 and 74years, compared to those over 75years (21% versus 26.6%,
respectively), but this was not statistically significant. These findings suggest
varying outcomes following scoliosis surgery in the elderly, but interpretation
of these results is weakened by the inherent limitations of database utilization.
Future prospective studies are needed to understand risk factors and other
confounding variables, such as discharge disposition, that may influence
outcomes.
PMID- 27612672
TI - Noninvasive assessment of the intracranial pressure in non-traumatic intracranial
hemorrhage.
AB - The article describes the modified technique of measuring the diameters of the
optic nerve sheath (ONSD) for assessment of the intracranial pressure (ICP) in
patients with intracerebral or subarachnoid hemorrhage (SAH). The CT scans of 443
patients were analyzed retrospectively. The ONSDs were measured at 3mm behind the
globe and at the point where the ophthalmic artery crosses the optic nerve. The
ONSD/eyeball transverse diameter (ETD) ratio was calculated. The correlation
analysis was performed with the Glasgow Coma Scale score, Hemispheric Stroke
Scale score, Glasgow Outcome Score, and invasive ICP readings. ONSD was enlarged
in 95% of patients with intracerebral hemorrhage or SAH. Pathological ONSDs were
6.6+/-0.8mm (cut-off value >5.5mm; p<0.05). ONSD/ETD ratio was 0.29+/-0.05
against normative 0.19+/-0.02 (p<0.01) with no correlation with initial Glasgow
Coma Scale score or Hemispheric Stroke Scale score. There was an inverse
correlation between ONSD/ETD ratio and Glasgow Outcome Score (r=-0.7) and direct
correlation with invasive ICP readings. This study provides further evidence that
in patients with intracranial hemorrhage and SAH, the presence of ONSD greater
than a threshold of 5.5mm is significantly predictive of invasively measured
elevated ICP. The prediction of raised ICP can be further refined by measuring
ONSD at the point where the optic nerve and the ophthalmic artery cross, and by
determining the ratio between the ONSD and ETD.
PMID- 27612673
TI - Multiple meningiomas in a woman irradiated in utero.
AB - Meningiomas are a common central nervous system tumour and radiation is a known
risk factor for their development. In utero radiation exposure correlates to
developmental abnormalities and carcinogenesis in a dose- and gestational age
related manner. Radiation induced meningioma has been reported in detail in the
literature in patients who had been irradiated earlier in life. At the time of
publication, there was no data on radiation exposure whilst in utero and
meningioma. We report on a 42-year-old woman with multiple intracranial
meningiomas and no other risk factors except a history of in utero exposure to
low dose X-ray radiation at 12weeks gestational age.
PMID- 27612674
TI - Visual pathway abnormalities in tuberculous meningitis.
AB - Ophthalmological complications are common and disabling in patients with
tuberculous meningitis. We aimed to study the visual pathway abnormalities in
patients with tuberculous meningitis. Forty-three patients with tuberculous
meningitis were subjected to visual evoked responses (VER) and
neuroophthalmologic assessment. Neuroophthalmologic assessment revealed
abnormalities in 22 (51.3%) patients. VER were found to be abnormal in 27 (62.8%)
patients. The VER abnormalities included prolonged P100 latencies with relatively
normal amplitude and significant interocular latency differences. Visual pathways
abnormalities are common in patients with tuberculous meningitis and are often
subclinical. Pathophysiologic explanations for electrophysiological abnormalities
on VER in these patients are incompletely understood and needs further
exploration.
PMID- 27612675
TI - Demineralizing potential of dental biofilm added with Candida albicans and
Candida parapsilosis isolated from preschool children with and without caries.
AB - This study aimed to investigate the demineralizing potential of dental biofilm
added of Candida albicans (CA) and Candida parapsilosis (CP), isolated from
preschoolers with and without caries. Bovine enamel blocks (n = 48), with initial
hardness = 341.50 +/- 21,83 kg/mm2 were fixed in 24 well plates containing
culture media. A pool of children saliva (PHS) was the inoculum for biofilm
formation in the presence or absence of isolated CA or CP in accordance with each
group (G n = 8): G1 - PHS; G2 - PHS + CA isolated from children with caries; G3 -
PHS + CP isolated from children with caries; G4 - PHS + CA isolated from children
without caries; G5 - PHS + CP isolated from children without caries; and G6 -
blank control. The plates were incubated at 37 degrees C for 5 days, with daily
changes of culture media. The microhardness loss percentage (MHL%) of the blocks
was calculated, taking in account the hardness values before and after the
experiment. Dental biofilm became more cariogenic, independently of the isolated
Candida species. The highest MHL% was observed in G4 (85.90 +/- 8.72%) and G5
(86.13 +/- 6.74%) compared to the others (p < 0.001): G1 (34.30 +/- 14,30%) < G2
(59.40 +/- 10.56%) and G3 (65.80 +/- 6.36%) < G6 (13.68 +/- 4.86%) (p < 0.001).
C. albicans and C. parapsilosis isolates induced the demineralization of the
dental enamel.
PMID- 27612676
TI - Prognostic significance of circulating leukocyte subtype counts in patients with
coronary artery disease.
AB - BACKGROUND AND AIMS: This study investigated the association of leukocyte subtype
counts with vascular endothelial dysfunction and future cardiovascular events in
patients with coronary artery disease (CAD). METHODS: The study included 389
consecutive CAD patients (259 male, 130 female; mean age, 70.1 +/- 9.9 years).
The patients underwent coronary angiography, and measurement of blood parameters,
including leukocyte subtype counts. RESULTS: There were 84 cardiovascular events
during a mean follow-up of 586 +/- 378 days. Kaplan-Meier analysis showed a
higher probability of cardiovascular events in the high-monocyte group
(>=360/mm3) compared with the low-monocyte group (<360/mm3) (log-rank test, p =
0.047). Multivariate Cox hazard analysis identified a high monocyte count as an
independent predictor of cardiovascular events (hazard ratio: 1.63, 95%
confidence interval:1.05-2.51, p = 0.028). Peripheral endothelial function in 355
of the CAD patients was assessed by reactive hyperemia peripheral arterial
tonometry index (RHI) to examine the association of ln-RHI with leukocyte subtype
counts. Total leukocyte, monocyte and neutrophil counts were significantly higher
in CAD patients with low ln-RHI (<0.57: the mean ln-RHI value) compared with
those with high ln-RHI (>=0.57). Univariate analyses revealed that ln-RHI in CAD
patients was positively correlated with ln-total leukocyte (r = -0.187, p <
0.001), ln-monocyte (r = 0.316, p < 0.001), and neutrophil (r = -0.175, p =
0.001) counts. Multiple regression analysis showed that the monocyte count was a
significant and independent factor associated with ln-RHI (adjusted R2 = 0.126, p
< 0.001). CONCLUSIONS: A high monocyte count was an independent and incremental
predictor of cardiovascular events in CAD patients. The monocyte count was also
significantly correlated with peripheral endothelial dysfunction in CAD patients.
PMID- 27612678
TI - What is an intensive care unit? A report of the task force of the World
Federation of Societies of Intensive and Critical Care Medicine.
AB - Since their widespread introduction more than half a century ago, intensive care
units (ICUs) have become an integral part of the health care system. Although
most ICUs are found in high-income countries, they are increasingly a feature of
health care systems in low- and middle-income countries. The World Federation of
Societies of Intensive and Critical Care Medicine convened a task force whose
objective was to answer the question "What is an ICU?" in an internationally
meaningful manner and to develop a system for stratifying ICUs on the basis of
the intensity of the care they provide. We undertook a scoping review of the peer
reviewed and gray literature to assemble existing models for ICU stratification.
Based on these and on discussions among task force members by teleconference and
2 face-to-face meetings, we present a proposed definition and classification of
ICUs. An ICU is an organized system for the provision of care to critically ill
patients that provides intensive and specialized medical and nursing care, an
enhanced capacity for monitoring, and multiple modalities of physiologic organ
support to sustain life during a period of life-threatening organ system
insufficiency. Although an ICU is based in a defined geographic area of a
hospital, its activities often extend beyond the walls of the physical space to
include the emergency department, hospital ward, and follow-up clinic. A level 1
ICU is capable of providing oxygen, noninvasive monitoring, and more intensive
nursing care than on a ward, whereas a level 2 ICU can provide invasive
monitoring and basic life support for a short period. A level 3 ICU provides a
full spectrum of monitoring and life support technologies, serves as a regional
resource for the care of critically ill patients, and may play an active role in
developing the specialty of intensive care through research and education. A
formal definition and descriptive framework for ICUs can inform health care
decision-makers in planning and measuring capacity and provide clinicians and
patients with a benchmark to evaluate the level of resources available for
clinical care.
PMID- 27612677
TI - Implementing genomics and pharmacogenomics in the clinic: The National Human
Genome Research Institute's genomic medicine portfolio.
AB - Increasing knowledge about the influence of genetic variation on human health and
growing availability of reliable, cost-effective genetic testing have spurred the
implementation of genomic medicine in the clinic. As defined by the National
Human Genome Research Institute (NHGRI), genomic medicine uses an individual's
genetic information in his or her clinical care, and has begun to be applied
effectively in areas such as cancer genomics, pharmacogenomics, and rare and
undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future
of genomic research, including an ambitious research agenda to facilitate and
promote the implementation of genomic medicine. To realize this agenda, NHGRI is
consulting and facilitating collaborations with the external research community
through a series of "Genomic Medicine Meetings," under the guidance and
leadership of the National Advisory Council on Human Genome Research. These
meetings have identified and begun to address significant obstacles to
implementation, such as lack of evidence of efficacy, limited availability of
genomics expertise and testing, lack of standards, and difficulties in
integrating genomic results into electronic medical records. The six research and
dissemination initiatives comprising NHGRI's genomic research portfolio are
designed to speed the evaluation and incorporation, where appropriate, of genomic
technologies and findings into routine clinical care. Actual adoption of
successful approaches in clinical care will depend upon the willingness,
interest, and energy of professional societies, practitioners, patients, and
payers to promote their responsible use and share their experiences in doing so.
PMID- 27612679
TI - Careers in Industry: Pioneering Spirit Prevails at the Carlsberg Research
Laboratory.
AB - The founder of the Carlsberg brewery, J.C Jacobsen, recognized the value of
private-public partnership and established the Carlsberg Foundation in 1876 with
the single aim of applying research and innovation to brew the best beer. One
hundred and forty years on, Jacobsen's vision still prevails, and in this
interview three scientists from the Carlsberg Research Laboratory (Birgitte
Skadhauge, Anna Haldrup, and Ole Olsen) share their experience about finding a
career at the crossroads between industry and basic research.
PMID- 27612680
TI - Early Development Challenges for Drug Products Containing Nanomaterials.
AB - The vast majority of drug product candidates in early development fail to
progress to clinics. This is true for products containing nanomaterials just as
for other types of pharmaceuticals. Early development pathways should therefore
place high priority on experiments that help candidates fail faster and less
expensively. Nanomedicines fail for many reasons, but some are more avoidable
than others. Some of the points of failure are not considerations in the
development of small molecules or biopharmaceuticals, and so may be unexpected,
even to those with previous experience bringing drug products to the clinic. This
article reviews experiments that have proven useful in providing "go/no-go"
decision-making data for nanomedicines in early preclinical development. Of
course, the specifics depend on the particulars of the drug product and the
nanomaterial type, and not every product shares the same development pathway or
the same potential points of failure. Here, we focus on challenges that differ
from those in the development of traditional small molecule therapeutics, and on
experiments that reveal deficiencies that can only be corrected by essentially
starting over-altering the nanomedicine to an extent that all previous
characterization and proof-of-concept testing must be repeated. Conducting these
experiments early in the development process can save significant resources and
time and allow developers to focus on derisked candidates with a greater
likelihood of ultimate success.
PMID- 27612681
TI - The Use of Exosomes as Biomarkers for Evaluating and Monitoring Critically Ill
Polytrauma Patients with Sepsis.
AB - Regarding genetic biomarkers for early assessment and monitoring the clinical
course in polytrauma patients with sepsis, in recent years a remarkable evolution
has been highlighted. One of the main representatives is the exosome miRNAs. In
this paper, we would like to present in more details the various methods of using
exosome miRNAs as a biomarker for monitoring polytrauma patients with sepsis, as
well as establishing a belated outcome by aggregating the entire clinical
aspects. The use of exosome miRNAs for late evaluating and monitoring the
clinical evolution of polytrauma patients can bring significant improvements in
current clinical practice through the optimization and modulation of intensive
care according to the needs of each patient individually.
PMID- 27612682
TI - Simultaneous determination of ascorbic acid, acetaminophen and codeine based on
multi-walled carbon nanotubes modified with magnetic nanoparticles paste
electrode.
AB - Based on incorporating ZnCrFeO4 into multi-walled carbon nanotubes paste matrix
(MWCNTs/ZnCrFeO4/CPE), a chemically modified electrode was prepared for the
simultaneous determination of ascorbic acid (AA), acetaminophen (AC) and codeine
(CO). The prepared electrode, MWCNTs/ZnCrFeO4/CPE, was characterized by scanning
electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The
MWCNTs/ZnCrFeO4/CPE showed an efficient electrocatalytic activity for the
oxidation of AA, AC, and CO. The separations of the oxidation peak potentials for
AA-AC and AC-CO were about 250mV and 630mV, respectively. The calibration curves
obtained for AA, AC, and CO were in the ranges of 0.4-730.0MUmolL(-1), 0.1
368.0MUmolL(-1), and 0.3-250.0MUmolL(-1), respectively. The detection limits
(S/N=3) were 0.03MUmolL(-1), 0.009MUmolL(-1), and 0.01MUmolL(-1) for AA, AC, and
CO, respectively. The method was also successfully employed as a selective,
simple, and precise method to determinate AA, AC, and CO in pharmaceutical and
biological samples.
PMID- 27612683
TI - In-vitro depth-dependent hyperthermia of human mammary gland adenocarcinoma.
AB - Nanoparticle mediated photothermal ablation of cancerous tissue shows promising
results and applicability as a highly efficacious treatment method. As a majority
of the photothermal work has been conducted with minimal attenuation of the laser
before reaching the nanoparticles within surface seeded tumors in-vivo or through
buffered media in-vitro, it is important to understand the effects of greater
laser attenuation on photothermal efficacy mediated by changes in the scattering
and absorption of the laser. Photothermal efficacy using a near infrared (NIR)
785nm laser irradiating polystyrene (PS) stabilized magnetite (Fe3O4)
nanoparticles (PS-Fe3O4) is examined on MDA-MB-231 human mammary gland
adenocarcinoma in-vitro. Agarose gel columns of various heights were created to
simulate soft tissue and subsequently used for NIR laser attenuation. Polystyrene
was found to significantly improve magnetite nanoparticle stability in serum
containing media and modified Hank's Balanced Salt Solution and was able to
induce significant hyperthermic ablation at mass concentrations which also did
not elicit significant innate toxicity. Furthermore it was found that the
polystyrene coating significantly reduced innate toxicity over 48h compared to
uncoated magnetite. Agar gel layers provided similar optical attenuation in the
NIR region to skin and prostate.
PMID- 27612684
TI - Multifunctional nanocrystalline calcium phosphates loaded with Tetracycline
antibiotic combined with human adipose derived mesenchymal stromal stem cells
(hASCs).
AB - Osteoconductive drug delivery system composed of nanocrystalline calcium
phosphates (Ca10(PO4)6(OH)2/beta-Ca3(PO4)2) co-doped with Yb(3+)/Er(3+) ions
loaded with Tetracycline antibiotic (TC) was developed. Their effect on human
adipose derived mesenchymal stromal stem cells (hASCs) as a potential
reconstructive biomaterial for bone tissue regeneration was studied. The XRD and
TEM measurements were used in order to determine the crystal structure and
morphology of the final products. The characteristics of nanocomposites with the
TC and hASCs as potential regenerative materials as well as the antimicrobial
activity of the nanoparticles against: Staphylococcus aureus ATCC 25923 as a
model of the Gram-positive bacteria, Escherichia coli ATCC 8739 of the Gram
negative bacteria, were shown. These combinations can be a promising material for
theranostic due to its regenerative, antimicrobial and fluorescent properties.
PMID- 27612685
TI - Modulation, functionality, and cytocompatibility of three-dimensional printing
materials made from chitosan-based polysaccharide composites.
AB - The mechanical properties, cytocompatibility, and fabrication of three
dimensional (3D) printing strips of composite materials containing polylactide
(PLA) and chitosan (CS) were evaluated. Maleic anhydride-grafted polylactide (PLA
g-MA) and CS were used to enhance the desired characteristics of these
composites. The PLA-g-MA/CS materials exhibited better mechanical properties than
the PLA/CS composites; this effect was attributed to a greater compatibility
between the grafted polyester and CS. The water resistance of the PLA-g-MA/CS
composites was greater than that of the PLA/CS composites; cytocompatibility
evaluation with human foreskin fibroblasts (FBs) indicated that both materials
were nontoxic. Moreover, CS enhanced the antibacterial activity properties of PLA
g-MA and PLA/CS composites.
PMID- 27612686
TI - A composite hydrogel system containing glucose-responsive nanocarriers for oral
delivery of insulin.
AB - Development of an oral delivery strategy for insulin therapeutics has drawn much
attention in recent years. In this study, a glucose-responsive nanocarriers for
loading of insulin has been prepared firstly. The resultant nanocarriers
exhibited relative low cytotoxicity against Caco-2 cells and excellent stability
against protein solution. The insulin release behaviors were evaluated triggered
by pH and glucose in vitro. In order to enhance the oral bioavailability of
insulin, the insulin-loaded glucose-responsive nanocarriers were further
encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel
environment for overcoming multiple barriers and providing multi-protection for
insulin during the transport process. The hypoglycemic effect for oral delivery
of insulin was studied in vivo. After oral administration to the diabetic rats,
the released insulin from hydrogel systems containing insulin-loaded glucose
responsive nanocarriers exhibited an effective hypoglycemic effect for longer
time compared with insulin-loaded nanocarriers.
PMID- 27612687
TI - Development of Co-based bulk metallic glasses as potential biomaterials.
AB - A new series of Co80-x-yCrxMoyP14B6 (x=5 y=5; x=5 y=10; x=10 y=10, all values in
at.%) bulk metallic glasses (BMGs) with a maximum diameter of 1.5mm has been
developed for using them as potential bio-implant materials by a combination of
fluxing treatment and J-quenching technique. The performance of the present Co
based BMGs in biomedical implant applications was investigated as compared to the
CoCrMo biomedical alloy (ASTM F75) and 316L stainless steel (316L SS). The
corrosion behavior of the samples was investigated in both Hank's solution
(pH=7.4) and artificial saliva solution (pH=6.3) at 37 degrees C employing
electrochemical measurements. The results indicate that the Co-based BMGs exhibit
much higher corrosion resistance in the simulated body solutions than that of
316L SS. Compared with the corrosion resistance of ASTM F75, that of
Co70Cr5Mo5P14B6 and Co65Cr5Mo10P14B6 BMGs is found to be lower and that of
Co60Cr10Mo10P14B6 BMG is higher. The concentrations of Co, Cr, and Mo ions
released into the simulated body solutions from our Co-based BMGs after
potentiodynamic polarization are significantly lower than that released from ASTM
F75. The biocompatibility of the specimens was evaluated using an in vitro test
of NIH3T3 cell culture in the specimen extraction media for 1, 3, 5, and 7days,
revealing the non-cytotoxicity of the Co-based BMGs towards NIH3T3 cells.
Moreover, examinations on the cell adhesion and growth on the surface of the
specimens indicate that the Co-based BMGs exhibit better cell viability compared
to ASTM F75 and 316L SS biomedical alloys.
PMID- 27612688
TI - Influence of heavy nanocrystals on spermatozoa and fertility of mammals.
AB - In recent years, quantum dots (QDs) have been widely used in upcoming
nanotechnology-based solar cells, light-emitting diodes and even bioimaging, due
to their tunable optical properties and excellent quantum yields. But, such
nanostructures are currently constituted by heavy elements which can threat the
human health and living environment. Hence, in this work, the in vivo effects of
CdTe nanocrystals (NCs) (as one of the promising QDs) on spermatozoa of male mice
and subsequently on fertility of female mice were investigated, for the first
time. To do this, CdTe NCs were synthesized through an environment-friendly
(aqueous-based solution) method. The sperm cells presented a high potential for
uptake of the heavy QDs. Meantime, the NCs exhibited concentration-dependent
adverse effects on morphology, viability, kinetic characteristics and DNA of the
spermatozoa. At low concentration of 0.1MUg/mL, the NCs showed a moderate
toxicity (~25% reduction in viability and motility of the spermatozoa), while
remarkable toxicities were observed at higher concentrations of 1.0-100MUg/mL
(~67% reduction in viability and motility for 100MUg/mL). Furthermore,
significant in vitro DNA fragmentation of the spermatozoa was observed at CdTe
concentrations >=10MUg/mL. In vivo toxicity of the NCs was found lower than the
in vitro toxicity. Nevertheless, the in vivo destructive effects of the NCs still
caused ~34% reduction in viability as well as motility and ~5% damages in DNA of
male mice spermatozoa. These resulted in ~26% decrease in fertility and gestation
of female mice, along with an overall hormone secretion during the pregnancy, and
~39% reduction in viability of pups/pregnant females.
PMID- 27612690
TI - Solid inclusion complexes of oleanolic acid with amino-appended beta
cyclodextrins (ACDs): Preparation, characterization, water solubility and
anticancer activity.
AB - Oleanolic acid (OA) is a pentacyclic triterpenoid acid of natural abundance in
plants which possesses important biological activities. However, its medicinal
applications were severely impeded by the poor water solubility and resultant low
bioavailability and potency. In this work, studies on solid inclusion complexes
of OA with a series of amino-appended beta-cyclodextrins (ACDs) were conducted in
order to address this issue. These complexes were prepared by suspension method
and were well characterized by NMR, SEM, XRD, TG, DSC and Zeta potential
measurement. The 2:1 inclusion mode of ACDs/OA complexes was elucidated by
elaborate 2D NMR (ROESY). Besides, water solubility of OA was dramatically
promoted by inclusion complexation with ACDs. Moreover, in vitro anticancer
activities of OA against human cancer cell lines HepG2, HT29 and HCT116 were
significantly enhanced after formation of inclusion complexes, while the
apoptotic response results indicated their induction of apoptosis of cancer
cells. This could provide a novel approach to development of novel pharmaceutical
formulations of OA.
PMID- 27612689
TI - Propoxylation of cationic polymers provides a novel approach to controllable
modulation of their cellular toxicity and interaction with nucleic acids.
AB - An effective chemical approach to modulation of biological interactions of
cationic polymers was proposed and tested using polyethyleneimine (PEI) as a drug
carrier. Branched 25kDa PEI was modified in the reaction with propylene oxide
(PO) to produce a series of propoxylated PEIs with NH groups grafted by single or
oligomer PO units. Clear relationships between the propoxylation degree and
biological effects, such as interaction with plasmid DNA, hemolytic, cytotoxic,
and pro-apoptotic activities were revealed for PEIs modified upon PO/NH molar
ratio of 0.5, 0.75, 1.0 and 3.0. The partial modification of available cationic
centers up to 100% is predominantly accompanied by a significant gradual
reduction in polycation adverse effects, while ability of complex formation with
plasmid DNA is being preserved. Grafted PEI with 0.75 PO/NH ratio provides better
protection from nuclease degradation and transfection activity compared with
other modified PEIs. Revealed relationships contribute to the development of safe
polymeric systems with controllable physicochemical properties and biological
interactions.
PMID- 27612691
TI - Monitoring the evolution of boron doped porous diamond electrode on flexible
retinal implant by OCT and in vivo impedance spectroscopy.
AB - Nanocrystalline Boron doped Diamond proved to be a very attractive material for
neural interfacing, especially with the retina, where reduce glia growth is
observed with respect to other materials, thus facilitating neuro-stimulation
over long terms. In the present study, we integrated diamond microelectrodes on a
polyimide substrate and investigated their performances for the development of
neural prosthesis. A full description of the microfabrication of the implants is
provided and their functionalities are assessed using cyclic voltammetry and
electrochemical impedance spectroscopy. A porous structure of the electrode
surface was thus revealed and showed promising properties for neural recording or
stimulation. Using the flexible implant, we showed that is possible to follow in
vivo the evolution of the electric contact between the diamond electrodes and the
retina over 4months by using electrochemical impedance spectroscopy. The position
of the implant was also monitored by optical coherence tomography to corroborate
the information given by the impedance measurements. The results suggest that
diamond microelectrodes are very good candidates for retinal prosthesis.
PMID- 27612692
TI - Sunlight assisted synthesis of silver nanoparticles in zeolite matrix and study
of its application on electrochemical detection of dopamine and uric acid in
urine samples.
AB - Sunlight assisted reduction of silver ions were accomplished for the synthesis of
silver nanoparticles incorporated within the mesoporous silicate framework of
zeolite Y. The zeolite-Y and AgNP/Zeo-Y were characterized by field emission
scanning electron microscopy, transmission electron microscopy, N2 adsorption
desorption BET isotherm and X-ray diffraction techniques. The incorporation of
silver nanoparticles within the porous framework was further confirmed by cyclic
voltammetry and electrochemical impedance spectroscopy. An enhanced
electrocatalytic oxidation of biologically important molecules like dopamine and
uric acid using AgNP/Zeo-Y modified glassy carbon electrode has been developed. A
simultaneous oxidation of DA and UA peaks were obtained at +0.31V and +0.43V (vs.
Ag/AgCl) using AgNP/Zeo-Y/GCE under the optimum experimental condition. A well
resolved peak potential window (~120mV) for the oxidation of both DA and UA were
observed at AgNP/Zeo-Y/GCE system. The calibration curves for DA and UA were
obtained within the dynamic linear range of 0.02*10(-6) to 0.18*10(-6)M
(R(2)=0.9899) and 0.05*10(-6) to 0.7*10(-6)M (R(2)=0.9996) and the detection
limits were found to be 1.6*10(-8)M and 2.51*10(-8)M by using differential pulse
voltammetry (DPV) method. The proposed method was successfully applied for the
determination of both DA and UA in human urine samples with a related standard
deviation was <3%, and n=5 using the standard addition method.
PMID- 27612693
TI - Comparison study of different coatings on degradation performance and cell
response of Mg-Sr alloy.
AB - To solve the problem of rapid degradation for magnesium-based implants, surface
modification especially coating method is widely studied and showed the great
potential for clinical application. However, as concerned to the further
application and medical translation for biodegradable magnesium alloys, there are
still lack of data and comparisons among different coatings on their degradation
and biological properties. This work studied three commonly used coatings on Mg
Sr alloy, including micro-arc oxidation coating, electrodeposition coating and
chemical conversion coating, and compared these coatings for requirements of
favorable degradation and biological performances, how each of these coating
systems has performed. Finally the mechanism for the discrepancy between these
coatings is proposed. The results indicate that the micro-arc oxidation coating
on Mg-Sr alloy exhibited the best corrosion resistance and cell response among
these coatings, and is proved to be more suitable for the orthopedic application.
PMID- 27612694
TI - Enhanced bioactivity, biocompatibility and mechanical behavior of strontium
substituted bioactive glasses.
AB - Strontium contained biomaterials have been reported as a potential bioactive
material for bone regeneration, as it reduces bone resorption and stimulates bone
formation. In the present investigation, the bioactive glasses were designed to
partially substitute SrO for SiO2 in Na2O-CaO-SrO-P2O5-SiO2 system. This work
demonstrates that the substitution of SrO for SiO2 has got significant benefit
than substitution for CaO in the bioactive glass. Bioactivity was assessed by the
immersion of the samples in simulated body fluid for different intervals. The
formation of hydroxy carbonate apatite layer was identified by X-ray
diffractometry, scanning electron microscopy (SEM) and energy dispersive
spectroscopy. The elastic modulus of the bioactive glasses was measured and found
to increase with increasing SrO for SiO2. The blood compatibility of the samples
was evaluated. In vitro cell culture studies of the samples were performed using
human osteosarcoma U2-OS cell lines and found a significant improvement in cell
viability and proliferation. The investigation showed enhancement in bioactivity,
mechanical and biological properties of the strontia substituted for silica in
glasses. Thus, these bioactive glasses would be highly potential for bone
regeneration.
PMID- 27612695
TI - The hydrogen-storing microporous silica 'Microcluster' reduces acetaldehyde
contained in a distilled spirit.
AB - Acetaldehyde is a detrimental substance produced in alcoholic liquor aging. We
assessed an ability of hydrogen-storing microporous silica 'Microcluster' (MC+)
to reduce acetaldehyde, as compared with autoclave-dehydrogenated MC+ (MC-).
Acetaldehyde was quantified spectrophotometrically by an enzymatic method.
Authentic acetaldehyde was treated by MC+ for 20min, and decreased from 43.4ppm
to 10.9ppm, but maintained at 49.3ppm by MC-. On the other hand, acetaldehyde
contained in a distilled spirit was decreased from 29.5ppm to 3.1ppm at 20min by
MC+, but not decreased by MC-. Addition of MC+ or MC- to distilled water without
acetaldehyde showed no seeming effect on the quantification used. Accordingly
acetaldehyde in a distilled spirit is reduced to ethanol by hydrogen contained in
MC+, but not by the silica moiety of MC+. Hydrogen gas of 1.2mL was released for
20min from MC+ of 0.59g in water, resulting in dissolved hydrogen of 1.09ppm and
an oxidation- reduction potential of -687.0mV indicative of a marked reducing
ability. Thus, MC+ has an ability to reduce acetaldehyde in a distilled spirit
due to dissolved hydrogen released from MC+.
PMID- 27612696
TI - Nanomolar detection of methylparaben by a cost-effective hemoglobin-based
biosensor.
AB - This work describes the development of a new biosensor for methylparaben
determination using electrocatalytic properties of hemoglobin in the presence of
hydrogen peroxide. The voltammetric oxidation of methylparaben by the proposed
biosensor in phosphate buffer (pH=7.0), a physiological pH, was studied and it
was confirmed that methylparaben undergoes a one electron-one proton reaction in
a diffusion-controlled process. The biosensor was fabricated by carbon paste
electrode modified with hemoglobin and multiwalled carbon nanotube. Based on the
excellent electrochemical properties of the modified electrode, a sensitive
voltammetric method was used for determination of methylparaben within a linear
range from 0.1 to 13MUmolL(-1) and detection limit of 25nmolL(-1). The developed
biosensor possessed accurate and rapid response to methylparaben and showed good
sensitivity, stability, and repeatability. Finally, the applicability of the
proposed biosensor was verified by methylparaben evaluation in various real
samples.
PMID- 27612697
TI - Voltammetric determination of 6-thioguanine and folic acid using a carbon paste
electrode modified with ZnO-CuO nanoplates and modifier.
AB - ZnO-CuO nanoplates and 2-chlorobenzoyl ferrocene, were synthesized and used to
construct a modified carbon paste electrode. The electrooxidation of 6
thioguanine at the surface of the modified electrode was studied. Under the
optimized conditions, the square wave voltammetric (SWV) peak current of 6
thioguanine increased linearly in the concentration range 0.05 to 200.0MUM and
detection limit of 25+/-2nM was obtained for 6-thioguanine. The prepared modified
electrode exhibits a very good resolution between the voltammetric peaks of 6
thioguanine and folic acid which makes it suitable for the detection of 6
thioguanine in the presence of folic acid in real samples.
PMID- 27612698
TI - A new antibacterial Co-Cr-Mo-Cu alloy: Preparation, biocorrosion, mechanical and
antibacterial property.
PMID- 27612699
TI - Cyclodextrin-polyhydrazine degradable gels for hydrophobic drug delivery.
AB - An injectable and biocompatible hydrogel system was designed for hydrophobic drug
delivery. This hydrogel consisted of degradable polymers with cyclodextrin (CD)
moieties. CD groups were used to increase the solubility of a hydrophobic
molecule (nicardipine) in an aqueous solution through the formation of the
inclusion complex. Two sets of gels were prepared by mixing oxidized dextran (DA)
and CD functionalized polyhydrazine (PH) at physiological conditions and
different level of crosslinking via hydrazone bonds. Cytotoxicity studies on the
gels and their components confirmed the biocompatibility of these materials. Gel
30 with higher crosslinking density showed a two week degradation period whereas
this period was 10days for gel-10, with lower crosslinking density, to complete
degradation. The results from swelling tests and rheological measurements were
also found to be dependent on crosslinking density of the hydrogels. Release
profile of the hydrogel displayed a sustained release of nicardipin up to 6days
for gel-30 and a 4day release with initial burst release for gel-10.
PMID- 27612700
TI - Porous magnesium loaded with gentamicin sulphate and in vitro release behavior.
AB - Our aim was to develop a biocompatible bone repair material that has the
advantage of preventing postoperative infections. Finally, the porous magnesium
(p-Mg) loaded with gentamicin sulphate (GS-loaded Mg-G) was fabricated. The GS
release behavior of the GS-loaded Mg-G in phosphate buffer saline (PBS) was
investigated. The effective release time of GS reached to 14days. In addition,
the effects of porosity and pore diameter of p-Mg on the GS release behavior of
the GS-loaded Mg-G were studied. In the initial burst release stage, the GS
release rate of the GS-loaded Mg-G increased with the increasing porosity or the
increasing pore diameter of p-Mg. The GS-loaded Mg-G with larger original pore
diameter has higher burst release of GS. Moreover, the in vitro antibacterial
test of the GS-loaded Mg-G indicated that this biomaterial has obvious
antibacterial effect. This study can provide information for p-Mg loaded with
drug(s) as functional bone repair materials with drug-delivery capabilities.
PMID- 27612701
TI - Self-healable mussel-mimetic nanocomposite hydrogel based on catechol-containing
polyaspartamide and graphene oxide.
AB - Stimuli-responsive and self-healing materials have a wide range of potential
uses, and some significant research has focused on cross-linking of hydrogel
materials by means of reversible coordination bonding. The resulting materials,
however, tend to have poor mechanical properties with pronounced weakness and
brittleness. In this work, we present a novel mussel-inspired graphene oxide(GO)
containing hydrogel based on modified polyaspartamide with gamma-amino butyric
acid (GABA), 3.4-dihydroxyphenethylamine (DOPA), and ethanolamine (EA), termed
PolyAspAm(GABA/DOPA/EA). Here both GO nanosheets and boric acid (H3BO3) act as
cross-linkers, interacting with polar functional groups of the
PolyAspAm(GABA/DOPA/EA). Compared to PolyAspAm(GABA/DOPA/EA)/B(3+) gel without
GO, the same containing 5wt% of GO yielded a 10-fold increase in both the storage
and loss moduli, as well as 134% and 104% increases in the tensile and
compressive strengths, respectively. In addition, the GO-containing
polyaspartamide hydrogel exhibited rapid and autonomous self-healing property.
Two types of bonding, boron-catechol coordination and strong hydrogen bonding
interactions between PolyAspAm side chains and GO nanosheets, would impart the
enhanced mechanical strength and good reversible gelation behavior upon pH
stimulation to the hydrogel, making this biocompatible hydrogel a promising soft
matter for biomedical applications.
PMID- 27612702
TI - Efficacy of the biomaterials 3wt%-nanostrontium-hydroxyapatite-enhanced calcium
phosphate cement (nanoSr-CPC) and nanoSr-CPC-incorporated simvastatin-loaded
poly(lactic-co-glycolic-acid) microspheres in osteogenesis improvement: An
explorative multi-phase experimental in vitro/vivo study.
AB - AIMS: The purpose of this multi-phase explorative in vivo animal/surgical and in
vitro multi-test experimental study was to (1) create a 3wt%-nanostrontium
hydroxyapatite-enhanced calcium phosphate cement (Sr-HA/CPC) for increasing bone
formation and (2) creating a simvastatin-loaded poly(lactic-co-glycolic acid)
(SIM-loaded PLGA) microspheres plus CPC composite (SIM-loaded PLGA+nanostrontium
CPC). The third goal was the extensive assessment of multiple in vitro and in
vivo characteristics of the above experimental explorative products in vitro and
in vivo (animal and surgical studies). METHODS AND RESULTS PERTAINING TO SR
HA/CPC: Physical and chemical properties of the prepared Sr-HA/CPC were
evaluated. MTT assay and alkaline phosphatase activities, and radiological and
histological examinations of Sr-HA/CPC, CPC and negative control were compared. X
ray diffraction (XRD) indicated that crystallinity of the prepared cement
increased by increasing the powder-to-liquid ratio. Incorporation of Sr-HA into
CPC increased MTT assay (biocompatibility) and ALP activity (P<0.05).
Histomorphometry showed greater bone formation after 4weeks, after implantation
of Sr-HA/CPC in 10 rats compared to implantations of CPC or empty defects in the
same rats (n=30, ANOVA P<0.05). METHODS AND RESULTS PERTAINING TO SIM-LOADED PLGA
MICROSPHERES+NANOSTRONTIUM-CPC COMPOSITE: After SEM assessment, the produced
composite of microspheres and enhanced CPC were implanted for 8weeks in 10
rabbits, along with positive and negative controls, enhanced CPC, and enhanced
CPC plus SIM (n=50). In the control group, only a small amount of bone had been
regenerated (localized at the boundary of the defect); whereas, other groups
showed new bone formation within and around the materials. A significant
difference was found in the osteogenesis induced by the groups sham control
(16.96+/-1.01), bone materials (32.28+/-4.03), nanostrontium-CPC (24.84+/-2.6),
nanostrontium-CPC-simvastatin (40.12+/-3.29), and SIM-loaded PLGA+nanostrontium
CPC (44.8+/-6.45) (ANOVA P<0.001). All the pairwise comparisons were significant
(Tukey P<0.01), except that of nanostrontium-CPC-simvastatin and SIM-loaded
PLGA+nanostrontium-CPC. This confirmed the efficacy of the SIM-loaded
PLGA+nanostrontium-CPC composite, and its superiority over all materials except
SIM-containing nanostrontium-CPC.
PMID- 27612703
TI - Enhanced cell adhesion on bioinert ceramics mediated by the osteogenic cell
membrane enzyme alkaline phosphatase.
AB - Functional bone and dental implant materials are required to guide cell response,
offering cues that provide specific instructions to cells at the implant/tissue
interface while maintaining full biocompatibility as well as the desired
structural requirements and functions. In this work we investigate the influence
of covalently immobilized alkaline phosphatase (ALP), an enzyme involved in bone
mineralization, on the first contact and initial cell adhesion. To this end, ALP
is covalently immobilized by carbodiimide-mediated chemoligation on two highly
bioinert ceramics, alpha-alumina (Al2O3) and yttria-stabilized zirconia (Y-TZP)
that are well-established for load-bearing applications. The physicochemical
surface properties are evaluated by profilometry, zeta potential and water
contact angle measurements. The initial cell adhesion of human osteoblasts
(HOBs), human osteoblast-like cells (MG-63) and mesenchymal stromal cells (hMSCs)
was investigated. Cell adhesion was assessed at serum free condition via
quantification of percentage of adherent cells, adhesion area and staining of the
focal adhesion protein vinculin. Our findings show that after ALP immobilization,
the Al2O3 and Y-TZP surfaces gained a negative charge and their hydrophilicity
was increased. In the presence of surface-immobilized ALP, a higher cell
adhesion, more pronounced cell spreading and a higher number of focal contact
points were found. Thereby, this work gives evidence that surface
functionalization with ALP can be utilized to modify inert materials for
biological conversion and faster bone regeneration on inert and potentially load
bearing implant materials.
PMID- 27612704
TI - The toughest recorded spider egg case silks are woven into composites with tear
resistant architectures.
AB - In this communication, we report important preliminary evidence for possibly the
toughest egg case silk threads recorded to date spun by the hermit spider,
Nephilengys cruentata (G-=193MJm(-3)). We further elucidate that the egg case
itself is woven with a specialised repeat cross-weave that when subjected to
tension, drives perpendicular-to-force threads to pile. This piling of threads
constrains damage to small areas and retains the architectural integrity of the
surrounding egg case material. We deduce that by having ultra-tough threads
coupled to a tear resistant architecture, N. cruentata is able to protect its
eggs from predators with a considerable level of effectiveness.
PMID- 27612705
TI - Self-assembling peptide hydrogels immobilized on silicon surfaces.
PMID- 27612706
TI - Physicochemical and mechanical properties of freeze cast hydroxyapatite-gelatin
scaffolds with dexamethasone loaded PLGA microspheres for hard tissue engineering
applications.
AB - Hydroxyapatite (HA)-gelatin scaffolds incorporated with dexamethasone-loaded
polylactic-co-glycolic acid (PLGA) microspheres were synthesized by freeze
casting technique. Scanning electron microscopy (SEM) micrographs demonstrated a
unidirectional microstructure and a decrease in the pore size as a function of
temperature gradient. Higher amounts of HA resulted in a decrease in the pore
size. According to the results, at lower cooling rates, the formation of a
lamellar structure decreased the mechanical strength, but at the same time,
enhanced the swelling ratio, biodegradation rate and drug release level. On the
other hand, higher weight ratios of HA increased the compressive strength, and
reduced the swelling ratio, biodegradation rate and drug release level. The
results obtained by furrier transform infrared spectroscopy (FTIR) and
bioactivity analysis illustrated that the interactions of the materials support
the apatite formation in the simulated body fluid (SBF) solution. Based on the
obtained results, the synthesized composite scaffolds have the necessary
mechanical and physicochemical features to support the regeneration of defects
and to maintain their stability during the neo-tissue formation.
PMID- 27612707
TI - Bifunctional impedimetric sensors based on azodicarboxamide supported on modified
graphene nanosheets.
AB - Herein, gold-coated graphene oxide nanosheets hybrid material (GO/AuNPs) with
exceptional physical and chemical properties has been utilized as a novel
platform for electrode modification. The synthetic method of GO/AuNPs involves
anon-covalent functionalization of exfoliated GO with AuNPs based on the
reduction of the Au(III) complex by sodium citrate. The prepared GO/AuNPs hybrid
exhibits the dispersion of high density AuNPs which were densely decorated on the
large surface area of GO. The GO/AuNPs modified glassy carbon (GC) electrode was
employed as a sensing platform to immobilize azodicarboxamide (ACA). The
morphology, structure and electrochemical performance of the sensor were
characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and
electrochemical impedance spectroscopy (EIS). The results indicate that the
modified electrode has a notable bifunctional catalytic activity.
Electrocatalytic oxidations of cysteine and electrocatalytic reduction of iodate
at the surface of modified electrode were investigated with different technique.
PMID- 27612708
TI - Potentiometric sensor fabrication having 2D sarcosine memories and analytical
features.
AB - In this study, a simple, rapid and sensitive method based on novel molecular
imprinted polymeric sensor has been developed and validated for the determination
of prostate cancer metabolite biomarker. The molecularly imprinted polymer (MIP)
has been synthesized by emulsion polymerization, using sarcosine as template
molecule, methacryloylamido histidine (MAH) as functional monomer and ethylene
glycol dimethacrylate (EDMA) as cross-linking agent. The performance of the
developed sarcosine sensor has been evaluated, and the results have indicated
that a sensitive potentiometric sensor has been fabricated. The sarcosine sensor
has showed high-selectivity, shorter response time (<2min), wider linear range
(10(-2)-10(-6)mM), lower detection limit (1.35*10(-7)mM), and satisfactory long
term stability (>5.5months).
PMID- 27612709
TI - A novel gel based on an ionic complex from a dendronized polymer and
ciprofloxacin: Evaluation of its use for controlled topical drug release.
AB - The development and characterization of a novel, gel-type material based on a
dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of
its possible use for controlled drug release, are presented in this work. DP
showed biocompatible and non-toxic behaviors in cultured cells, both of which are
considered optimal properties for the design of a final material for biomedical
applications. These results were encouraging for the use of the polymer loaded
with CIP (as a drug model), under gel form, in the development of a new
controlled-release system to be evaluated for topical administration. First, DP
CIP ionic complexes were obtained by an acid-base reaction using the high density
of carboxylic acid groups of the DP and the amine groups of the CIP. The
complexes obtained in the solid state were broadly characterized using FTIR
spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques.
Gels based on the DP-CIP complexes were easily prepared and presented excellent
mechanical behaviors. In addition, optimal properties for application on mucosal
membranes and skin were achieved due to their high biocompatibility and acute
skin non-irritation. Slow and sustained release of CIP toward simulated
physiological fluids was observed in the assays (in vitro), attributed to ion
exchange phenomenon and to the drug reservoir effect. An in vitro bacterial
growth inhibition assay showed significant CIP activity, corresponding to 38 and
58% of that exhibited by a CIP hydrochloride solution at similar CIP
concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa,
respectively. However, CIP delivery was appropriate, both in terms of magnitude
and velocity to allow for a bactericidal effect. In conclusion, the final product
showed promising behavior, which could be exploited for the treatment of topical
and mucosal opportunistic infections in human or veterinary applications.
PMID- 27612710
TI - In vivo degradation of a new concept of magnesium-based rivet-screws in the
minipig mandibular bone.
AB - Self-tapping of magnesium screws in hard bone may be a challenge due to the
limited torsional strength of magnesium alloys in comparison with titanium. To
avoid screw failure upon implantation, the new concept of a rivet-screw was
applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside
were expanded inside drill holes of minipig mandibles. During the expansion with
a hexagonal mandrel, the threads engaged the surrounding bone and the inside of
the screw transformed into a hexagonal screw drive to allow further screwing in
or out of the implant. The in vivo degradation of the magnesium implants and the
performance of the used coating were studied in a human standard-sized animal
model. Four magnesium alloy rivet-screws were implanted in each mandible of 12
minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy
implants; another six received the uncoated magnesium alloy rivet-screws. Two
further animals received one titanium rivet-screw each as control. In vivo
radiologic examination was performed at one, four, and eight weeks. Euthanasia
was performed for one group of seven animals (three animals with coated, three
with uncoated magnesium alloy implants and one with titanium implant) at 12weeks
and for the remaining seven animals at 24weeks. After euthanasia, micro-computed
tomography and histological examination with histomorphometry were performed.
Significantly less void formation as well as higher bone volume density (BV/TV)
and bone-implant contact area (BIC) were measured around the coated implants
compared to the uncoated ones. The surface coating was effective in delaying
degradation despite plastic deformation. The results showed potential for further
development of magnesium hollow coated screws for bone fixation.
PMID- 27612711
TI - Compressive failure modes and parameter optimization of the trabecular structure
of biomimetic fully integrated honeycomb plates.
AB - To develop lightweight biomimetic composite structures, the compressive failure
and mechanical properties of fully integrated honeycomb plates were investigated
experimentally and through the finite element method. The results indicated that:
fracturing of the fully integrated honeycomb plates primarily occurred in the
core layer, including the sealing edge structure. The morphological failures can
be classified into two types, namely dislocations and compactions, and were
caused primarily by the stress concentrations at the interfaces between the core
layer and the upper and lower laminations and secondarily by the disordered short
fiber distribution in the material; although the fully integrated honeycomb
plates manufactured in this experiment were imperfect, their mass-specific
compressive strength was superior to that of similar biomimetic samples.
Therefore, the proposed bio-inspired structure possesses good overall mechanical
properties, and a range of parameters, such as the diameter of the transition
arc, was defined for enhancing the design of fully integrated honeycomb plates
and improving their compressive mechanical properties.
PMID- 27612712
TI - A novel dual-frequency loading system for studying mechanobiology of load-bearing
tissue.
AB - In mechanobiological research, an appropriate loading system is an essential tool
to mimic mechanical signals in a native environment. To achieve this goal, we
have developed a novel loading system capable of applying dual-frequency loading
including both a low-frequency high-amplitude loading and a high-frequency low
amplitude loading, according to the mechanical conditions experienced by bone and
articular cartilage tissues. The low-frequency high-amplitude loading embodies
the main force from muscular contractions and/or reaction forces while the high
frequency low-amplitude loading represents an assistant force from small muscles,
ligaments and/or other tissue in order to maintain body posture during human
activities. Therefore, such dual frequency loading system may reflect the natural
characteristics of complex mechanical load on bone or articular cartilage than
the single frequency loading often applied during current mechanobiological
experiments. The dual-frequency loading system is validated by experimental tests
using precision miniature plane-mirror interferometers. The dual-frequency
loading results in significantly more solute transport in articular cartilage
than that of the low-frequency high-amplitude loading regiment alone, as
determined by quantitative fluorescence microscopy of tracer distribution in
articular cartilage. Thus, the loading system can provide a new method to mimic
mechanical environment in bone and cartilage, thereby revealing the in vivo
mechanisms of mechanosensation, mechanotransduction and mass-transport, and
improving mechanical conditioning of cartilage and/or bone constructs for tissue
engineering.
PMID- 27612713
TI - The composite hydrogels of polyvinyl alcohol-gellan gum-Ca(2+) with improved
network structure and mechanical property.
AB - The composite hydrogels of polyvinyl alcohol (PVA) and gellan gum (GG) are of
interesting in the biomaterials application. To improve the structure and
mechanical property, in this work, Ca(2+) ion was introduced to crosslink the
polymer chain, and the PVA-GG-Ca(2+) hydrogel was formed. By analyzing its
structure, mechanical properties, swelling and dehydration kinetics, the effect
of molecular interaction on hydrogel structure and properties have been observed.
Our result indicates that, as GG is added to hydrogel network, the role of Ca(2+)
ion is stand out, it reorganizes the network structure, enhances the mechanical
properties, and strengthens the electrolytic and hydrogen bonding interactions in
PVA-GG-Ca(2+) hydrogels. These observations will benefit the development of
hydrogels in biomaterials application.
PMID- 27612714
TI - Application of carbon nanotubes-ionic liquid hybrid in a sensitive atorvastatin
ion-selective electrode.
AB - Atorvastatin (ATR) was determined by a potentiometric method. The ion-pair of ATR
and cetyltrimethylammonium bromide (CTAB) was used as a suitable ionophore. A
graphite paste electrode was modified with ATR-CTAB ion-pair, multiwalled carbon
nanotubes (MWCNTs), and an ionic liquid, 1-butyl-3-mtehyl-imidazolium
hexafluorophosphate (BMIMPF6). The amounts of electrode ingredients were
optimized (graphite powder: paraffin oil: ATR-CTAB: MWCNTs: BMIMPF6 (58:26:5:8:3
w/w%). Surface characterization was done by using scanning electron microscopy.
The potential measurements were recorded at optimized pH by using acetate buffer
solution (0.1molL(-1), pH5.5). At the above experimental conditions, calibration
curve (E vs. log [ATR]) was linear (R(2)=0.9977) in the concentration range of
1.0*10(-9)-1.0*10(-3)molL(-1) (0.0012-1209mgL(-1)) of ATR with a Nernstian slope
of 58.14+/-0.2mV decade(-1), and detection limit of 1.0*10(-9)molL(-1)
(0.0013mgL(-1)). After each injection of ATR to the buffer solution, the
potential was stabilized in a very short time (average response time~6s) at 25
degrees C. The modified graphite paste electrode had a long lifetime (>4months).
Recovery of the spiked drug to blood serum samples (95.3-98.2%) revealed the
reliability of electrode response to ATR. Blood serum samples from consumers were
analyzed by the proposed method; the results were comparable with those from HPLC
standard method. The potentiometric analysis of ATR tablets by the proposed
electrode resulted in a relative error of 0.8% and 1.5% for 20 and 40mg per
tablets, respectively. Finally, the electrode was used in potentiometric
titration of ATR (1.0*10(-3)molL(-1)) by CTAB (1.0*10(-3)molL(-1)). Excellent
accuracy (~100%) was obtained from the volume of the titrant at the endpoint.
PMID- 27612715
TI - Vapor-based coatings for antibacterial and osteogenic functionalization and the
immunological compatibility.
AB - The immobilization of biofunctional molecules to biomaterial surfaces has enabled
and expanded the versatility of currently available biomaterials to a wider range
of applications. In addition, immobilized biomolecules offer modified surfaces
that allow the use of smaller amounts of potentially harmful substances or
prevent overdose, while the exhibited biological functions remain persistently
effective. Surface concentrations of chlorhexidine (CHX) (1.40+/-0.08*10(
9)mol.cm(-2)) and bone morphogenetic protein 2 (BMP-2) (1.51+/-0.08*10(
11)mol.cm(-2)) immobilized molecules were determined in this study, and their
specific biological functions in terms of antibacterial activity and osteogenesis
potency, respectively, were demonstrated to be unambiguously effective.
Immobilization exploits the use of vapor-based poly-p-xylylenes, which exhibit
excellent biocompatibility and wide applicability for various substrate
materials. This technique represents a practical and economical approach for the
manufacture of certain industrial products. Furthermore, a minimal degree of
macrophage activation was indicated on the modified surfaces via insignificant
morphological changes and low levels of adverse inflammatory signals, including
suppressed production of the pro-inflammatory cytokines IL-1beta and TNF-alpha as
well as nitric oxide (NO). The results and the modification strategy illustrate a
concept for designing prospective biomaterial surfaces such that the manipulation
employed to elicit targeted biological responses does not compromise
immunological compatibility.
PMID- 27612716
TI - Gated magnetic mesoporous silica nanoparticles for intracellular enzyme-triggered
drug delivery.
AB - The targeting drug release is significant to the anticancer treatment. In this
context, the redox-responsive drug delivery has attracted most attention owing to
the intracellular reductive environment, such as the high concentration of
glutathione reductase in many cancer cells. Herein, a glutathione sensitive drug
delivery nanoplatform was constructed by using core-shell mesoporous silica
nanocomposite (Fe3O4@mSiO2) as carrier. By a simple silane coupling reaction, the
glutathione cleavable diselenide linker has been prepared and grafted on to
Fe3O4@mSiO2 to insure the encapsulation of anticancer drug doxorubicin. The
detail release kinetics studies reveal the glutathione triggered drug release,
which could be further adjusted by varying the amount of diselenide linker. To
improve the tumor-targeting, folic acid was grafted. The cellular uptake and drug
release investigation was carried out using HeLa (cervical cancer cell line) as
the model cancer cell and L02 and HUVEC (human hepatic cell line and human
umbilical vein endothelial cells, non-cancerous cell lines) as control,
indicating the enhanced cytotoxicity toward HeLa cells that benefits from the
fast endocytosis and enhanced cellular drug release owing to their overexpressing
folic acid receptors and high concentration of glutathione. Associating with the
magnetic targeting, these novel nanomaterials are expected to be promising in the
potential application of tumor-targeting therapy.
PMID- 27612717
TI - Thermoplastic starch/ethylene vinyl alcohol/forsterite nanocomposite as a
candidate material for bone tissue engineering.
AB - Recently, biodegradable polymers such as starch based blends have been well
renowned in the biomedical field. Studies have considered them suitable for bone
scaffolds, bone cements, tissue engineering scaffolds, drug delivery systems and
hydrogels. The aim of this study was to synthesize nanocomposite biomaterial
consisting a blend of thermoplastic starch and ethylene vinyl alcohol as the
polymer matrix, and nano-structured forsterite as the ceramic reinforcing phase
for bone tissue engineering applications. Furthermore, vitamin E was applied as a
thermal stabilizer during melt compounding. Extrusion and injection molding were
incorporated for melt blending and shaping of samples, respectively. With
blending thermoplastic starch and ethylene vinyl alcohol, some properties of
thermoplastic starch such as degradation rate and water absorption were modified.
In addition, using nanoforsterite as the ceramic reinforcing phase resulted in
the improvement of mechanical and biological traits. The addition of
nanoforsterite decreased the weight loss of the thermoplastic starch and ethylene
vinyl alcohol blend in simulated body fluid. Moreover, this addition modified the
pH in the MTT (methyl thiazolyl tetrazolium) assay and stimulated the cell
proliferation. Cell adhesion assays indicated a favorable interaction between
cells and the biomaterial. The proposed nanocomposite has appropriate
biocompatibility, as well as mechanical properties in order to be used in bone
tissue engineering.
PMID- 27612718
TI - The effects of femtosecond laser-textured Ti-6Al-4V on wettability and cell
response.
AB - To study the biological activity effects of femtosecond laser-induced structures
on cell behavior, TA6V samples were micro-textured with focused femtosecond laser
pulses generating grooves of various dimensions on the micrometer scale (width:
25-75MUm; depth: 1-10MUm). LIPSS (Laser Induced Periodic Surface Structures) were
also generated during the laser irradiation, providing a supplementary structure
(sinusoidal form) of hundreds of nanometers at the bottom of the grooves oriented
perpendicular (? LIPPS) or parallel (// LIPPS) to the direction of these grooves.
C3H10 T1/2 murine mesenchymal stem cells were cultivated on the textured
biomaterials. To have a preliminary idea of the spreading of biological media on
the substrate, prior to cell culture, contact angle measurement were performed.
This showed that the post-irradiation hydrophilicity of the samples can decrease
with time according to its storage environment. The multiscale structuration
either induced a collaborative or a competitive influence of the LIPSS and
grooves on the cells. It has been shown that cells individually and collectively
were most sensitive to microscale grooves which were narrower than 25MUm and
deeper than 5MUm with ? LIPPS. In some cases, cells were individually sensitive
to the LIPSS but the cell layer organization did not exhibit significant
differences in comparison to a non-textured surface. These results showed that
cells are more sensitive to the nanoscale structures (LIPSS), unless the
microstructures's size is close to the cell size and deeper than 5MUm. There, the
cells are sensitive to the microscale structures and go on spreading following
these structures.
PMID- 27612719
TI - Amniotic epithelial stem cell biocompatibility for electrospun poly(lactide-co
glycolide), poly(epsilon-caprolactone), poly(lactic acid) scaffolds.
AB - Three biodegradable thermoplastic polymers, poly(epsilon-caprolactone) (PCL),
poly(l-lactide-co-d,l-lactide) (PLA) and poly(l-lactide-co-glycolide) (PLGA),
have been used to produce nonwovens scaffolds with uniform micrometer fibres.
Scaffolds' physical and morphological characterization was performed by X-ray
diffraction, Scanning Electron Microscopy and Contact-Angle test. Morphological
investigations revealed that all produced fibres were randomly orientated with
interconnected pores ranging between 5 and 12MUm in diameter. An average fibre
diameter of 1.5, 0.75 and 1.2MUm was found for PCL, PLA and PLGA, respectively.
Moreover, experiments were designed to verify whether the fabricated electrospun
substrates were biocompatible for ovine amniotic epithelial stem cells (oAECs)
under in vitro conditions. Cell adhesion, survival, spatial organization on
fibres, proliferation index, and DNA quantification after 48h culture, showed an
enhanced adhesion and proliferation, especially for PLGA scaffolds. The
favourable interaction between oAECs and the fibrous scaffolds was attributed to
the greatly improved porosity and pore size distribution of the electrospun
scaffolds. In addition, AECs can be considered ideal for tissue engineering
especially when using biocompatible and opportunely produced scaffolds.
PMID- 27612720
TI - Fabrication of autofluorescent porous silica nanoparticles for redox-responsive
drug release.
AB - Porous silica nanoparticles were prepared by emulsion-condensation route. The
silica nanoparticles with diameter of 50nm have both accessible center-radial
large pore channels (19.9nm) and small pore size of 3.5nm. The hierarchical
porous structure endows them large pore volume for loading drugs and sustained
release property. The silica nanoparticles were further modified with glucose
oxidized glutathione. The formulated Schiff base and disulfide bonds render the
silica nanoparticles auto-fluorescent and redox-responsive properties. The
cleavage of disulfide bonds caused by reactive thiols facilitates
aminomethylbenzoic acid (AMA) release. The release of drug leads to the loss of
fluorescence, which would be used to monitor the drug delivery and carrier
distribution.
PMID- 27612721
TI - Deposition of calcium phosphate coatings using condensed phosphates (P2O7(4-) and
P3O10(5-)) as phosphate source through induction heating.
AB - In present work condensed phosphates (P2O7(4-) and P3O10(5-)) were used as
phosphate source in induction heating to deposit calcium phosphate coatings. The
phase, morphology, and composition of different phosphate-related coatings were
characterized and compared using XRD, FTIR, and SEM analyses. Results showed that
P2O7(4-)formed calcium pyrophosphate hydrate coatings with interconnected cuboid
like particles. The as-deposited calcium tripolyphosphate hydrate coating with
P3O10(5-) was mainly composed of flower-like particles assembled by plate-like
crystals. The bioactivity and cytocompatibility of the coatings were also
studied. Moreover, the feasibility of using hybrid phosphate sources for
preparing and depositing coatings onto magnesium alloy was investigated.
PMID- 27612722
TI - Poly-dopamine-beta-cyclodextrin: A novel nanobiopolymer towards sensing of some
amino acids at physiological pH.
AB - A novel nanobiopolymer film was electrodeposited on the surface of glassy carbon
through cyclic voltammetry from dopamine, beta-cyclodextrin, and phosphate buffer
solution in physiological pH (7.40). The electrochemical behavior of polydopamine
Beta-cyclodextrin modified glassy carbon electrode was investigated for electro
oxidation and determination of some amino acids (l-Cysteine, l-Tyrosine, l
Glycine, and l-Phenylalanine). The modified electrode was applied for selected
amino acid detection at physiological pH using cyclic voltammetry, differential
pulse voltammetry and chronoamperometry, chronocoulometery. The linear
concentration range of the proposed sensor for the l-Glycine, l-Cysteine, l
Tyrosine, and l-Phenylalanine were 0.2-70, 0.06-0.2, 0.01-0.1, and 0.2-10MUM,
while low limit of quantifications were 0.2, 0.06, 0.01, and 0.2MUM,
respectively. The modified electrode shows many advantages as an amino acid
sensor such as simple preparation method without using any specific electron
transfer mediator or specific reagent, good sensitivity, short response time, and
long term stability.
PMID- 27612723
TI - A rheological and microstructural characterisation of bigels for cosmetic and
pharmaceutical uses.
AB - Bigels are biphasic systems formed by water-based hydrogels and oil-based
organogels, mainly studied, in the last few years, for pharmaceutical and
cosmetic application focused on the controlled delivery of both lipophilic and
hydrophilic active agents. The rheological properties of bigels depend on both
the amount and the rheological characteristics of single structured phases.
Moreover, it can be expected that, at large fractions of one of the starting
gels, systems more complex than oil-in-water or water-in-oil can be obtained,
yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were
investigated from a microstructural (i.e. microscopy and electrical conductivity
tests) and rheological point of view. The hydrogel was prepared by using a low
methoxyl pectin whereas the organogel was prepared by using olive oil and, as
gelator, a mixture of glyceryl stearate and policosanol. Model bigels were
obtained by increasing the amount of organogel mixed with the hydrogel, and
microstructural characterisation evidenced an organogel-in-hydrogel behaviour for
all investigated samples, even though at the highest organogel content a more
complex structure seems to arise. A semi-empirical model, based on theoretical
equations developed for suspensions of elastic spheres in elastic media, was
proposed to relate bigel rheological properties to single phase properties and
fractions.
PMID- 27612724
TI - Superior antibacterial activity of GlcN-AuNP-GO by ultraviolet irradiation.
AB - A complete bacterialysis analysis of glucosamine-gold nanoparticle-graphene oxide
(GlcN-AuNP-GO) and UV-irradiated GlcN-AuNP-GO was conducted. Analytical
characterization of GlcN-AuNPs, GO and GlcN-AuNP-GO revealed UV-Vis absorbance
peak at around 230 and 500nm. Microscopic characterization of prepared
nanomaterials was performed by scanning electron microscope, atomic force
microscopy, and high-resolution transmission microscopy. The results confirmed
that the GlcN-AuNPs were uniformly decorated on the surface and edges of graphene
sheets. In addition, potent antibacterial activity of GlcN-AuNP-GO that was UV
irradiated for 10min and normal GlcN-AuNP-GO was detected, compared to the
standard drug kanamycin, against both Gram-negative and positive bacteria. The
minimum inhibitory concentration (MIC) and fluorescence intensity spectra results
for Escherichia coli and Enterococcus faecalis showed that the UV-irradiated GlcN
AuNP-GO has better antibacterial activity than normal GlcN-AuNP-GO and kanamycin.
Morphological changes were detected by AFM after treatment. These results
confirmed that GlcN-AuNP-GO is a potent antibacterial agent with good potential
for use in manufacturing medical instruments, pharmaceutical industries and in
waste water treatment.
PMID- 27612725
TI - Improving cytoactive of endothelial cell by introducing fibronectin to the
surface of poly L-Lactic acid fiber mats via dopamine.
AB - A simple but straightforward approach was reported to prepare fiber mats modified
with fibronectin (Fn) protein for endothelial cells activity study. Based on the
self-polymerization and strong adhesion feature of dopamine, poly L-Lactic acid
(PLLA) fibers mat was modified via simply immersing them into dopamine solution
for 16h. Subsequently, Fn was immobilized onto the fiber mats surface by the
coupling reactive polydopamine (PDA) layer and Fn. Attenuated total reflectance
Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron
spectroscopy (XPS) were used to determine the chemical compositions of fiber mats
surface, which confirmed the successful immobilization of PDA and Fn molecules on
the fiber surface. Scanning electronic microscopy (SEM) was used to observe the
surface morphology changes after modification with PDA and Fn. The data of water
contact angle showed that the hydrophilicity of the fiber mats was improved after
surface modification. The data of in vitro cell culture proved that the PDA and
Fn modified surface significantly enhanced the adhesion, proliferation and cell
activity of endothelial cells on the fiber mats. And the release of tumor
necrosis factor-alpha (TNF-alpha) by endothelial cells on the modified surface
was suppressed compared to that on culture plate and PLLA film at 2 and 4days,
while the secretion of interleukin-1beta (IL-1beta) was increased compared to
that on culture plate and PLLA film at 2days.
PMID- 27612726
TI - Design and manufacture of neural tissue engineering scaffolds using hyaluronic
acid and polycaprolactone nanofibers with controlled porosity.
AB - Given the large differences in nervous tissue and other tissues of the human body
and its unique features, such as poor and/or lack of repair, there are many
challenges in the repair process of this tissue. Tissue engineering is one of the
most effective approaches to repair neural damages. Scaffolds made from
electrospun fibers have special potential in cell adhesion, function and cell
proliferation. This research attempted to design a high porous nanofibrous
scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions
for nerve regeneration by applying proper physicochemical and mechanical signals.
Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds
were measured by FTIR and tensile test. Morphology, swelling behavior, and
biodegradability of the scaffolds were evaluated too. Porosity of various layers
of scaffolds was measured by image analysis method. To assess the cell-scaffold
interaction, SH-SY5Y human neuroblastoma cell line were cultured on the
electrospun scaffolds. Taken together, these results suggest that the blended
nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet
all of the required specifications for neural cells and have potential
application in neural tissue engineering.
PMID- 27612727
TI - Rheological study of in-situ crosslinkable hydrogels based on hyaluronanic acid,
collagen and sericin.
AB - The elaboration of chemically crosslinked hydrogels based on collagen (C),
hyaluronanic acid (HA) and sericin (S) with different polymer ratios was
investigated by in-situ rheology. This reaction was performed via amide or ester
bond reaction activated by carbodiimide, in pure water. Prior to molecule
crosslinking, the rheological behaviour of the biopolymers (alone or in mixture)
was characterized in a semi-dilute concentration regime. Both flow and dynamic
measurements showed that uncrosslinked collagen alone appears to be rather
elastic with yield stress properties, whereas uncrosslinked HA alone appears to
be rather shear thinning and viscoelastic in agreement with entangled polymer
behaviour. Sericin exhibited Newtonian low viscosity behaviour according to its
very low molar mass. Before crosslinking, HA exhibited viscoelastic behaviour at
concentrations above the critical entangled concentration (C*) in the mixtures,
thus HA shows promise as a matrix for future crosslinked networks, whereas
sericin did not significantly modify the rheology. During the reaction, followed
by rheology, the kinetics were slower for pure HA systems compared with the
mixtures (i.e., with added collagen and/or to a lesser extent sericin). At the
same time, the final network of hydrogels (i.e., the elastic modulus) was more
structured in the mixture based systems. This result is explained by ester bonds
(the only possibility for pure HA systems), which are less favourable and
reactive than amide bonds (possible with sericin and collagen). The presence of
collagen in the HA matrix reinforced the hydrogel network. SEM studies confirmed
the structure of the hydrogels, and in vitro degradability was globally
consistent with the effect of the selected enzyme according to the hydrogel
composition. All the elaborated hydrogels were non-cytotoxic in vitro.
PMID- 27612728
TI - A reagentless non-enzymatic hydrogen peroxide sensor presented using
electrochemically reduced graphene oxide modified glassy carbon electrode.
AB - Herein, we report a simple, facile and reproducible non-enzymatic hydrogen
peroxide (H2O2) sensor using electrochemically reduced graphene oxide (ERGO)
modified glassy carbon electrode (GCE). The modified electrode was characterized
by Fourier transform infrared (FT-IR), UV-Visible, scanning electron microscopy
(SEM) and atomic force microscopy (AFM) techniques. Cyclic voltammetric (CV)
analysis revealed that ERGO/GCE exhibited virtuous charge transfer properties for
a standard redox systems and showed excellent performance towards
electroreduction of H2O2. Amperometric study using ERGO/GCE showed high
sensitivity (0.3MUA/MUM) and faster response upon the addition of H2O2 at an
applied potential of -0.25V vs. Ag/AgCl. The detection limit is assessed to be
0.7MUM (S/N=3) and the time to reach a stable study state current is <3s for a
linear range of H2O2 concentration (1-16MUM). In addition, the modified electrode
exhibited good reproducibility and long-term stability.
PMID- 27612729
TI - Research on a Zn-Cu alloy as a biodegradable material for potential vascular
stents application.
AB - Zn-based alloys have been viewed as new potential materials for biodegradable
implants, such as cardiovascular stents, mainly in consideration of their lower
corrosion rate when compared with that of Mg alloys. In this study we developed a
new Zinc-4wt.%Copper (Zn-4Cu) alloy as a biodegradable material. Hot extrusion
was applied to Zn-4Cu to refine the microstructure and consequently improve its
mechanical properties and corrosion resistance. After extrusion, dendritic CuZn5
phases were broken and distributed along the extrusion direction. The grains were
refined obviously due to dynamical recrystallization. The yield strength (YS),
ultimate tensile strength (UTS) and elongation of the as-extruded alloy are 250+/
10MPa, 270+/-10MPa and 51+/-2%, respectively. The corrosion rate of the as
extruded alloy in Hank's solution is about 9.41(+/-1.34)MUmyear(-1). In vitro
evaluation shows that Zn-4Cu presents acceptable toxicity to human endothelial
cells, and could effectively inhibit bacteria adhesion and biofilm formation. The
present study indicates that the as-extruded Zn-4Cu alloy exhibits excellent
strength and ductility, uniform and slow degradation, good biocompatibility and
significant antibacterial effect, which make it an excellent candidate material
for biodegradable implants, especially for cardiovascular stents application.
PMID- 27612730
TI - The potential of photo-deposited silver coatings on Foley catheters to prevent
urinary tract infections.
AB - Catheter-associated urinary tract infection (CAUTI) represents one of the most
common causes of morbidity and mortality. The resistance demonstrated by many
microorganisms to conventional antibiotic therapies and the increasing health
care costs have recently encouraged the definition of alternative preventive
strategies, which can have a positive effect in the management of infections.
Antimicrobial urinary catheters have been developed through the photo-chemical
deposition of silver coatings on the external and luminal surfaces. The
substrates are exposed to ultraviolet radiation after impregnation into a silver
based solution, thus inducing the in situ synthesis of silver particles. The
effect of the surface treatment on the material was investigated through scanning
electron microscopy (SEM) and silver ion release measurements. The ability of
microorganisms commonly associated with urinary tract infections was investigated
in terms of bacterial viability, proliferation and biofilm development, using
Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis as target
organisms. The silver coatings demonstrated good distribution of silver particles
to the substrate, and proved an effective antibacterial capability in simulated
biological conditions. The low values of silver ion release demonstrated the
optimum adhesion of the coating. The results indicated a good potential of silver
based antimicrobial materials for prevention of catheter-associated urinary tract
infection.
PMID- 27612731
TI - A cell-compatible PEO-PPO-PEO (Pluronic(r))-based hydrogel stabilized through
secondary structures.
AB - Pluronic F-127 (PF127) is a thermosensitive polymer that has been widely
recognized as a potential candidate for various bio-applications. However, in
hydrogel form, its rapid disintegration and inhospitality toward cells have
significantly limited its usage. As a means to increase the integrity and cell
compatibility of a PF127 hydrogel, we propose the introduction of stabilizing
secondary structures to the gel network by the addition of secondary structure
forming oligo-alanine and oligo-phenylalanine. Results indicate that increasing
the oligo(peptides) attached to PF127 led to a significant decrease in the
gelation concentration and temperature. A selected oligo(peptide)-modified PF127
was capable of forming a stable hydrogel network at 5% and suffered only 20%
weight loss after 7days of incubation in media. Scanning electron microscopy
(SEM) revealed comparably more interconnected morphology in modified hydrogels
which may be attributed to the presence of secondary structures, as verified by
circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy.
Nuclear magnetic resonance (NMR) provided insights into the extensive
interactions at the micelle core, which is the key to altered gelation behavior.
Furthermore, modified hydrogels maintained structural integrity within culturing
media and supported the proliferation of encapsulated chondrocytes. In addition,
in vivo residence time was extended to well beyond 2weeks after oligo(peptide)
modification, thereby broadening the application scope of the PF127 hydrogel to
encompass long-term drug delivery and cell culturing.
PMID- 27612732
TI - Synthesis of silver nanoparticles using aqueous extracts of Heterotheca inuloides
as reducing agent and natural fibers as templates: Agave lechuguilla and silk.
AB - Silver nanoparticles (Ag NPs) were synthesized using a one-pot green methodology
with aqueous extract of Heterotheca inuloides as a reducing agent, and the
support of natural fibers: Agave lechuguilla and silk. UV-Vis spectroscopy, X-Ray
photoelectron spectroscopy XPS and transmission electron microscopy TEM were used
to characterize the resulting bionanocomposite fibers. The average size of the Ag
NPs was 16nm and they exhibited low polydispersity. XPS studies revealed the
presence of only metallic Ag in the nanoparticles embedded in Agave. lechuguilla
fibers. Significant antibacterial activities against gram-negative Escherichia
coli and gram-positive Staphylococcus aureus were determined. AgO as well as
metallic Ag phases were detected when silk threads were used as a substrates
hinting at the active role of substrate during the nucleation and growth of Ag
NPs. These bionanocomposites have excellent mechanical properties in tension
which in addition to the antibacterial properties indicate the potential use of
these modified natural fibers in surgical and biomedical applications.
PMID- 27612733
TI - Biocompatibility and biomechanical characteristics of loofah based scaffolds
combined with hydroxyapatite, cellulose, poly-l-lactic acid with chondrocyte-like
cells.
AB - The current study reports the biocompatibility and biomechanical characteristics
of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-l
lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope
(SEM) micrographs of the scaffolds showed that the addition of PLLA usually
resulted in an increase in cell's attachment on scaffolds. Mechanical and
elemental analyzes were assessed using tensile test and Energy Dispersive X-ray
spectrometry (EDS), respectively. In summary, we showed that the loofah+PLLA+HA
scaffolds perform significantly better than other loofah-based scaffolds employed
in terms of increasing a diversity of mechanical properties including tensile
strength and Young's modulus. Based on the analysis of the differential scanning
calorimetry (DSC) thermograms and EDS spectrums that give an idea about the
calcium phosphate (CaP) ratios, the improvement in the mechanical properties
could principally be recognized to the strong interaction formed between loofah,
PLLA and HA. The viability of chondrocytes on loofah-based scaffolds was analyzed
by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic
activity. The histological evaluation obtained by hematoxylin and eosin (H&E),
Masson trichrome, toluidine blue and immunohistochemistry methods showed that
cells in all scaffolds produced extracellular matrix that defined proteoglycan
and type I-II collagens. The results of this study suggest that the loofah-based
scaffold with desirable properties can be considered as an ideal candidate for
cartilage tissue engineering applications.
PMID- 27612734
TI - Porous graphene oxide nanostructure as an excellent scaffold for label-free
electrochemical biosensor: Detection of cardiac troponin I.
AB - Herein, we report the fabrication of a novel label-free impedimetric biosensor
employing porous graphene oxide (PrGO) nanostructures for the specific detection
of cardiac troponin-I (cTnI) to establish the myocardial infarction (MI). This
nano-immunosensor demonstrates an outstanding selectivity and high sensitivity
towards the human-cTnI analyte. An excellent detection limit of 0.07ngmL(-1) and
dynamic linear range of 0.1-10ngmL(-1) were calculated for anti-cTnI/PrGO/GC.
Finally, this biosensor was employed to check the concentration of the MI
biomarker in real clinical samples and the results are in good agreement with
standard enzyme-linked fluorescence assay (ELFA) method.
PMID- 27612735
TI - Highly sensitive and selective determination of methylergometrine maleate using
carbon nanofibers/silver nanoparticles composite modified carbon paste electrode.
AB - A highly sensitive and selective voltammetric method for determination of
Methylergometrine maleate (MM) in pharmaceutical formulations, urine and blood
serum samples has been developed based on enhanced electrochemical response of MM
at carbon nanofibers and silver nanoparticles modified carbon paste electrode
(CNF-AgNP-CPE). The electrode material was characterized by various techniques
viz., X-ray diffraction, scanning electron microscopy and energy dispersive X-ray
spectroscopy. The electrocatalytic response of MM at CNF-AgNP-CPE was studied by
cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical
impedance spectroscopy (EIS). Under optimized conditions, the proposed sensor
exhibits excellent electrochemical response towards MM. The DPV study shows
greatly enhanced electrochemical signal for MM at CNF-AgNP-CPE lending high
sensitivity to the proposed sensor for MM detection. The peak (Ip) current for MM
is found to be rectilinear in the range 4.0*10(-8)-2.0*10(-5)M with a detection
limit of 7.1*10(-9)M using DPV. The feasibility of the proposed sensor in
analytical applications was investigated by conducting experiments on commercial
pharmaceutical formulations, human urine and blood serum samples, which yielded
satisfactory recoveries of MM. The proposed electrochemical sensor offers high
sensitivity, selectivity, reproducibility and practical utility. We recommend it
as an authentic and productive electrochemical sensor for successful
determination of MM.
PMID- 27612736
TI - Fabrication of silver nanoparticles embedded into polyvinyl alcohol (Ag/PVA)
composite nanofibrous films through electrospinning for antibacterial and surface
enhanced Raman scattering (SERS) activities.
AB - Silver nanoparticle-embedded polyvinyl alcohol (PVA) nanofibers were prepared
through electrospinning technique, using as antimicrobial agents and surface
enhanced Raman scattering (SERS) substrates. Ag nanoparticles (NPs) were
synthesized in liquid phase, followed by evenly dispersing in PVA solution. After
electrospinning of the mixed solution at room temperature, the PVA embedded with
Ag NPs (Ag/PVA) composite nanofibers were obtained. The morphologies and
structures of the as-synthesized Ag nanoparticles and Ag/PVA fibers were
characterized by the techniques of transmission electron microscopy (TEM), X-ray
diffraction (XRD), ultraviolet-visible absorption spectroscopy (UV-vis), Fourier
transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and
energy-dispersive X-ray spectroscopy (EDX). Ag NPs have an average diameter of
13.8nm, were found to be uniformly dispersed in PVA nanofibers. The Ag/PVA
nanofibers provided robust antibacterial activities against both Gram-positive
Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli)
microorganisms. It's also found that Ag/PVA nanofibers make a significant
contribution to the high sensitivity of SERS to 4-mercaptophenol (4-MPh)
molecules.
PMID- 27612737
TI - Development of a methacrylate-terminated PLGA copolymer for potential use in
craniomaxillofacial fracture plates.
AB - We synthesised methacrylate-terminated PLGA (HT-PLGA, 85:15 LA:GA, 169kDa), for
potential use as an adhesively attached craniomaxillofacial fracture fixation
plate. The in vitro degradation of molecular weight, pH and flexural modulus were
measured over 6weeks storage in PBS at 37 degrees C, with commercially available
high (225kDa, H-PLGA) and low (116kDa, L-PLGA) molecular weight 85:15 PLGAs used
as comparators. Molecular weights of the materials reduced over 6weeks, HT-PLGA
by 48%, H-PLGA by 23% and L-PLGA by 81%. HT-PLGA and H-PLGA exhibited a near
constant pH (7.35) and had average flexural moduli in excess of 6GPa when
produced, similar to that of the mandible. After 1week storage both exhibited a
significant reduction in average modulus, however, from weeks 1-6 no further
significant changes were observed, the average modulus never dropped
significantly below 5.5GPa. In contrast, the L-PLGA caused a pH drop to below 7.3
by week 6 and an average modulus drop to 0.6 from an initial 4.6GPa. Cell culture
using rat bone marrow stromal cells, revealed all materials were cytocompatible
and exhibited no osteogenic potential. We conclude that our functionalised PLGA
retains mechanical properties which are suitable for use in craniofacial fixation
plates.
PMID- 27612738
TI - Gelatin-carboxymethyl tamarind gum biocomposites: In vitro characterization &
anti-inflammatory pharmacodynamics.
AB - In this study, gelatin and carboxymethyl tamarind gum (CTG) were chemically cross
linked to control the delivery of aceclofenac from their interpenetrating network
(IPNs). Infrared spectra, thermal and X-ray data supported that drug and polymer
was compatible in the composite hydrogels. Irregularly shaped IPN microstructures
were seen under field emission scanning electron microscope (FE-SEM). IPN system
was capable of entrapping about 96% of the drug fed. CTG in IPN structures
suppressed the drug release rate in HCl solution (pH1.2); however extended the
same in phosphate buffer solution (pH6.8). The drug release was controlled by
polymer chain relaxation/swelling and simple diffusion in vitro. The anti
inflammatory activity of drug-loaded biocomposites lasted over 7h in albino rats,
thus suggesting their potential as an anti-inflammatory therapeutics.
PMID- 27612739
TI - Nanostructured silicate substituted calcium phosphate (NanoSiCaPs) nanoparticles
Efficient calcium phosphate based non-viral gene delivery systems.
AB - Nanostructured ceramic particles, particularly, nanoparticles of calcium
phosphate (CaP) remain an attractive option among the various types of non-viral
gene delivery vectors studied because of their safety, biocompatibility,
biodegradability, and ease of handling as well as their adsorptive capacity for
DNA. We have accordingly developed an enhanced version of nanostructured calcium
phosphates (NanoCaPs), by substituting known amounts of silicate for phosphate in
the hydroxyapatite (HA) lattice (NanoSiCaPs). Results indicate that in addition
to the excellent transfection levels exhibited by un-substituted NanoCaPs alone
in vitro, an additional 20-50% increase in transfection is observed for NanoCaPs
containing 8.3-50mol% silicate aptly called NanoSiCaPs, owing to its rapid
dissolution properties enabling nanoparticles escaping the lysosomal degradation.
However, high silicate substitution (>50mol%) resulted in a drastic decline in
transfection as the synthesized NanoCaPs deviated far from the characteristic
hydroxyapatite phase formed as evidenced by the materials characterization
results.
PMID- 27612740
TI - Mussel-inspired alginate gel promoting the osteogenic differentiation of
mesenchymal stem cells and anti-infection.
AB - Alginate hydrogels have been used in cell encapsulation for many years but a
prevalent issue with pure alginates is that they are unable to provide enough
bioactive properties to interact with mammalian cells. This paper discusses the
modification of alginate with mussel-inspired dopamine for cell loading and anti
infection. Mouse bone marrow stem cells were immobilized into alginate and
alginate-dopamine beads and fibers. Through live-dead and MTT assay, alginates
modified by dopamine promoted cell viability and proliferation. In vitro cell
differentiation results showed that such an alginate-dopamine gel can promote the
osteogenic differentiation of mesenchymal stem cell after PCR and ALP assays. In
addition to that, the adhesive prosperities of dopamine allowed for coating the
surface of alginate-dopamine gel with silver nanoparticles, which provided the
gel with significant antibacterial characteristics. Overall, these results
demonstrate that a dopamine-modified alginate gel can be a great tool for cell
encapsulation to promote cell proliferation and can be applied to bone
regeneration, especially in contaminated bone defects.
PMID- 27612741
TI - Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with
improved compressive strength for bone regeneration.
AB - In this study we have fabricated porous injectable spherical scaffolds using
chitosan biopolymer, sodium tripolyphosphate (TPP) and nano-hydroxyapatite (nHA).
TPP was primarily used as an ionic crosslinker to crosslink nHA/chitosan
droplets. We hypothesized that incorporating nHA into chitosan could support
osteoconduction by emulating the mineralized cortical bone structure, and improve
the Ultimate Compressive Strength (UCS) of the scaffolds. We prepared chitosan
solutions with 0.5%, 1% and 2% (w/v) nHA concentration and used simple
coacervation and lyophilization techniques to obtain spherical scaffolds.
Lyophilized spherical scaffolds had a mean diameter of 1.33mm (n=25). Further,
portion from each group lyophilized scaffolds were soaked and dried to obtain
Lyophilized Soaked and Dried (LSD) scaffolds. LSD scaffolds had a mean diameter
of 0.93mm (n=25) which is promising property for the injectability. Scanning
Electron Microscopy images showed porous surface morphology and interconnected
pore structures inside the scaffolds. Lyophilized and LSD scaffolds had surface
pores <10 and 2MUm, respectively. 2% nHA/chitosan LSD scaffolds exhibited UCS of
8.59MPa compared to UCS of 2% nHA/chitosan lyophilized scaffolds at 3.93MPa.
Standardize UCS values were 79.98MPa and 357MPa for 2% nHA/chitosan lyophilized
and LSD particles respectively. One-way ANOVA results showed a significant
increase (p<0.001) in UCS of 1% and 2% nHA/chitosan lyophilized scaffolds
compared to 0% and 0.5% nHA/chitosan lyophilized scaffolds. Moreover, 2% nHA LSD
scaffolds had significantly increased (p<0.005) their mean UCS by 120% compared
to 2% nHA lyophilized scaffolds. In a drawback, all scaffolds have lost their
mechanical properties by 95% on the 2nd day when fully immersed in phosphate
buffered saline. Additionally live and dead cell assay showed no cytotoxicity and
excellent osteoblast attachment to both lyophilized and LSD scaffolds at the end
of 14th day of in vitro studies. 2% nHA/chitosan scaffolds showed higher
osteoblast attachment than 0% nHA/chitosan scaffolds.
PMID- 27612742
TI - Novel bioactive Fe-based metallic glasses with excellent apatite-forming ability.
AB - We demonstrate, for the first time, that the (Fe0.75B0.15Si0.1)100-xNbx (x=0, 1
and 3at.%) metallic glasses without toxic and allergic elements exhibit excellent
apatite-forming ability in simulated body fluids (SBF), which is expected to be a
new generation of biomaterials in stents and orthopedic implants. For the alloys
without any surface treatment, spherical particles corresponding to octacalcium
phosphate are spontaneously nucleated and precipitated throughout the alloy
surface after immersion only for 1day, indicating that the present alloys possess
an unusual high bioactivity. During the subsequent in-vitro immersion for 3days,
SEM image reveals the typical 'cauliflower' morphology of bone-like
hydroxyapatite (HA) with Ca/P ratio of 1.65. In addition, it is surprising to
find that the in-vitro SBF immersion not only leads to the formation and growth
of the apatite layer but also causes the progressive development of the
underlying alloy substrate. Moreover, for the alloys immersed for 3 or 9days, the
substrate alloy just beneath the apatite layer consists of a hierarchical
nano/macro-porous structure through selective dissolution of the active
components Fe and B in the surface. XPS analysis indicates that the apatite
nucleation on the present alloys in SBF is attributed to the specific dissolution
properties of the present alloys and the fast formation of Si-OH and Fe-OH or Nb
OH functional groups, followed by combination of these groups with Ca(2+) and
phosphate ions.
PMID- 27612743
TI - Proteomic profile of mouse fibroblasts exposed to pure magnesium extract.
AB - Magnesium and its alloys gain wide attention as degradable biomaterials. In order
to reveal the molecular mechanism of the influence of biodegradable magnesium on
cells, proteomics analysis was performed in this work. After mouse fibroblasts
(L929) were cultured with or without Mg degradation products (Mg-extract) for 8,
24, and 48h, changes in protein expression profiles were obtained using isobaric
tags for relative and absolute quantitation (iTRAQ) coupled two dimensional
liquid chromatography-tandem mass spectrometry (2D LC MS/MS). A total of 867
proteins were identified (relying on at least two peptides). Compared to the
control group, 205, 282, and 217 regulated proteins were identified at 8, 24, and
48h, respectively. 65 common proteins were up or down- regulated within all the
three time points, which were involved in various physiological and metabolic
activities. Consistent with viability, proliferation, and cell cycle analysis,
stimulated energy metabolism as well as protein synthesis pathways were
discussed, indicating a possible effect of Mg-extract on L929 proliferation.
Furthermore, endocytosis and focal adhesion processes were also discussed. This
proteomics study uncovers early cellular mechanisms triggered by Mg degradation
products and highlights the cytocompatibility of biodegradable metallic materials
for biomedical applications such as stents or orthopaedic implants.
PMID- 27612744
TI - Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery.
AB - This study reports a novel one pot synthesis of pH-responsive nanocarrier for
oral delivery of hydrophobic drug under gastrointestinal tract. Triblock
copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using
hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was
attached to polybuthadiene backbone by thiol-ene click reaction in a facile and
convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self
organized into micelle assemblies in the water. The size and shape of the micelle
assemblies were confirmed by dynamic light scattering (DLS) and transmission
electron microscopy (TEM). The nanocarriers have high drug loading ability for
poorly water-soluble drug. The pH-responsive profile was demonstrated by pH
dependent swelling and in vitro drug release. <10.0% IBU was released under
artificial gastric fluid after 2h, whereas an immediate release was observed
under artificial intestinal fluid. The XTT assay indicated that the micelle
obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range
of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG
triblock copolymers are promising nanocarriers for the oral administration of
hydrophobic drugs.
PMID- 27612745
TI - Evaluation of bone loss in antibacterial coated dental implants: An experimental
study in dogs.
AB - The aim of this study was to evaluate the in vivo effect of antibacterial
modified dental implants in the first stages of peri-implantitis. Thirty dental
implants were inserted in the mandibular premolar sites of 5 beagle dogs. Sites
were randomly assigned to Ti (untreated implants, 10units), Ti_Ag (silver
electrodeposition treatment, 10units), and Ti_TSP (silanization treatment,
10units). Coated implants were characterized by scanning electron microscopy,
interferometry and X-ray photoelectron spectroscopy. Two months after implant
insertion, experimental peri-implantitis was initiated by ligature placement.
Ligatures were removed 2months later, and plaque formation was allowed for 2
additional months. Clinical and radiographic analyses were performed during the
study. Implant-tissue samples were prepared for micro computed tomography,
backscattered scanning electron microscopy, histomorphometric and histological
analyses and ion release measurements. X-ray, SEM and histology images showed
that vertical bone resorption in treated implants was lower than in the control
group (P<0.05). This effect is likely due to the capacity of the treatments to
reduce bacteria colonization on the implant surface. Histological analysis
suggested an increase of peri-implant bone formation on silanized implants.
However, the short post-ligature period was not enough to detect differences in
clinical parameters among implant groups. Within the limits of this study,
antibacterial surface treatments have a positive effect against bone resorption
induced by peri-implantitis.
PMID- 27612746
TI - Substance P incorporation in calcium phosphate cement for dental alveolar bone
defect restoration.
AB - A combination of osteoinductive neuropeptide substance P (SP) and osteoconductive
bone cement of calcium phosphate (CPC) might provide an effective and lower-cost
solution for complex alveolar bone defects restoration. The present study aims to
investigate the key design considerations of SP delivery in CPC. In this study,
CPC-based modular scaffolds were developed, where collagen type I was used as
accessory organic ingredient to modulate the physical and biological characters.
SP was directly mixed in the cement as free peptides, or was covalently
immobilized with collagen component. The structural and mechanical properties of
the scaffolds were assessed in vitro, and their osteogenic ability was observed
in a rabbit model with alveolar bone defect. The results showed that SP could
enhance the osteo-conductivity/inductivity of CPC. Collagen solution optimized
biocompatibility of CPC, and meanwhile exhibited additive effects on the
functions of SP. Nevertheless, immobilization of SP with collagen blocked their
bioactivity in CPC. Collagen sponges created macro-porosity in CPC and achieved
maximum bone ingrowth with the aid of SP. In conclusion, the present study
primarily demonstrated that CPC scaffold can be functionalized by synthetic SP,
and the biocompatibility and porosity of the scaffold are adaptable key factors
determining their final osteogenic activities.
PMID- 27612747
TI - Effects of polydeoxyribonucleotides (PDRN) on wound healing: Electric cell
substrate impedance sensing (ECIS).
AB - Polydeoxyribonucleotides (PDRN) have been explored as an effective treatment for
tissue repair in peripheral artery occlusive disease, diabetic foot ulcers, and
eye lotion. We report on the effect of polydeoxyribonucleotides (PDRN) on wound
healing by using the electric cell-substrate impedance sensing (ECIS) system and
viability testing. Human osteoblasts (U2OS) and primary human dermal fibroblasts
(HDF) were used to study the effect of PDRN on migration and proliferation. ECIS
allowed the creation of a wound by applying high current, and then monitoring the
healing process by measuring impedance in real time. The traditional culture
insert gap-closure migration assay was performed and compared with the ECIS wound
assay. PDRN-treated U2OS and HDF cells affected cell motilities to wounding site.
Viability test results show that HDF and U2OS proliferation depended on PDRN
concentration. Based on the results, a PDRN compound can be useful in wound
healing associated with bone and skin.
PMID- 27612748
TI - Grafting polyethylenimine with quinoline derivatives for targeted imaging of
intracellular Zn(2+) and logic gate operations.
AB - In this study, a highly sensitive and selective fluorescent Zn(2+) probe which
exhibited excellent biocompatibility, water solubility, and cell-membrane
permeability, was facilely synthesized in a single step by grafting
polyethyleneimine (PEI) with quinoline derivatives. The primary amino groups in
the branched PEI can increase water solubility and cell permeability of the probe
PEIQ, while quinoline derivatives can specifically recognize Zn(2+) and reduce
the potential cytotoxicity of PEI. Basing on fluorescence off-on mechanism, PEIQ
demonstrated excellent sensing capability towards Zn(2+) in absolute aqueous
solution, where a high sensitivity with a detection limit as low as 38.1nM, and a
high selectivity over competing metal ions and potential interfering amino acids,
were achieved. Inspired by these results, elementary logic operations (YES, NOT
and INHIBIT) have been constructed by employing PEIQ as the gate while Zn(2+) and
EDTA as chemical inputs. Together with the low cytotoxicity and good cell
permeability, the practical application of PEIQ in living cell imaging was
satisfactorily demonstrated, emphasizing its wide application in fundamental
biology research.
PMID- 27612749
TI - Novel PGS/PCL electrospun fiber mats with patterned topographical features for
cardiac patch applications.
AB - Nano- and micro-scale topographical features play a critical role in the
induction and maintenance of various cellular properties and functions, including
morphology, adhesion, gene regulation, and cell-to-cell communication. In
addition, recent studies have indicated that the structure and function of heart
tissue are also sensitive to mechanical cues at the nano- and micro-scale.
Although fabrication methods exist for generating topographical features on
polymeric scaffolds for cell culture, current techniques, especially those with
nano-scale resolution, are typically complex, prohibitively expensive and not
accessible to most biology laboratories. Here, we present a simple and tunable
fabrication method for the production of patterned electrospun fibers that
simulate the complex anisotropic and multi-scale architecture of cardiac tissue,
to promote cardiac cell alignment. This method is based on the combination of
electrospinning and soft lithography techniques, in which electrospun fibers,
based on a blend of poly(glycerol sebacate) and poly(caprolactone), were
collected on a patterned Teflon-coated silicon wafer with imprinted topographical
features. Different surface topographies were investigated, such as squares and
grooves, with constant or different interspatial distances. In vitro cell culture
studies successfully demonstrated the alignment of both C2C12 myoblasts and
neonatal rat cardiomyocytes on fabricated electrospun patterned surfaces. C2C12
cells were cultured over a period of 72h to study the effect of topographical
cues on cell morphology. Cells attached within the first 8h after seeding and
after 24h most of the cells started to align responding to the topographical
cues. Similarly, cardiomyocytes responded to the topographical features by
aligning themselves and by expressing Connexin 43 along cellular junctions.
Summarizing, we have developed a new method with the potential to significantly
promote cardiac tissue engineering by fabricating electrospun fibers with defined
topographical features to guide and instruct donor and/or host cells.
PMID- 27612750
TI - Methotrexate intercalated calcium carbonate nanostructures: Synthesis, phase
transformation and bioassay study.
AB - The formation and stabilization of amorphous calcium carbonate (ACC) is an active
area of research owing to the presence of stable ACC in various biogenic
minerals. In this paper, the synthesis of calcium carbonate (CaCO3) under the
participation of methotrexate (MTX) via a facile gas diffusion route was
reported. The results indicated that the addition of MTX can result in the phase
transformation of CaCO3, and then two kinds of hybrids, i.e., MTX-vaterite and
stable MTX-ACC came into being. Interestingly, the functional agent MTX served as
both the target anticancer drug loaded and effective complexation agents to
modify and control the morphology of final samples. The examination of MTX-ACC
biodegradation process revealed that the collapse of MTX-ACC nanoparticles was
due to the synergistic effect of drug release and the phase transformation.
Finally, our study also proved that MTX-ACC exhibited the most excellent
suppressing function on the viability of cancer cells, especially after long-time
duration.
PMID- 27612751
TI - Cytotoxicity assessment of adipose-derived mesenchymal stem cells on synthesized
biodegradable Mg-Zn-Ca alloys.
AB - Magnesium (Mg)-based alloys have been extensively considered as biodegradable
implant materials for orthopedic surgery. Mg and its alloys are metallic
biomaterials that can degrade in the body and promote new bone formation. In this
study, the corrosion behavior and cytotoxicity of Mg-Zn-Ca alloys are evaluated
with adipose-derived mesenchymal stem cells (ASCs). Mg-2Zn and Mg-2Zn-xCa (x=1, 2
and 3wt.%) alloys were designated. Mg alloys were analyzed with scanning electron
microscopy and potentiodynamic polarization. To understand the in-vitro
biocompatibility and cytotoxicity of Mg-2Zn and Mg-2Zn-xCa alloys, ASCs were
cultured for 24 and 72h in contact with 10%, 50% and 100% extraction of all
alloys prepared in DMEM. Cell cytotoxicity and viability of ASCs were examined by
MTT assay. Alloying elements including Zn and Ca improved the corrosion
resistance of alloys were compared with pure Mg. The cytotoxicity results showed
that all alloys had no significant adverse effects on cell viability in 24h.
After 72h, cell viability and proliferation increased in the cells exposed to
pure Mg and Mg-2Zn-1Ca extracts. The release of Mg, Zn and Ca ions in culture
media had no toxic impacts on ASCs viability and proliferation. Mg-2Zn-1Ca alloy
can be suggested as a good candidate to be used in biomedical applications.
PMID- 27612752
TI - Optimization of preparation method for ketoprofen-loaded microspheres consisting
polymeric blends using simplex lattice mixture design.
AB - In the present investigation, simplex lattice mixture design was applied for
formulation development and optimization of a controlled release dosage form of
ketoprofen microspheres consisting polymers like ethylcellulose and
Eudragit((r))RL 100; when those were formed by oil-in-oil emulsion solvent
evaporation method. The investigation was carried out to observe the effects of
polymer amount, stirring speed and emulsifier concentration (% w/w) on percentage
yield, average particle size, drug entrapment efficiency and in vitro drug
release in 8h from the microspheres. Analysis of variance (ANOVA) was used to
estimate the significance of the models. Based on the desirability function
approach numerical optimization was carried out. Optimized formulation (KTF-O)
showed close match between actual and predicted responses with desirability
factor 0.811. No adverse reaction between drug and polymers were observed on the
basis of Fourier transform infrared (FTIR) spectroscopy and Differential scanning
calorimetric (DSC) analysis. Scanning electron microscopy (SEM) was carried out
to show discreteness of microspheres (149.2+/-1.25MUm) and their surface
conditions during pre and post dissolution operations. The drug release pattern
from KTF-O was best explained by Korsmeyer-Peppas and Higuchi models. The batch
of optimized microspheres were found with maximum entrapment (~90%), minimum loss
(~10%) and prolonged drug release for 8h (91.25%) which may be considered as
favourable criteria of controlled release dosage form.
PMID- 27612753
TI - Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive
properties.
AB - Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end
composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol
(PEG) blend was developed for biomedical applications especially as an
alternative of advanced tissue scaffold. The developed composite film was
subjected to mechanical, thermal and physico-chemical characterization such as
tensile strength (TS) and elongation at break (Eb), differential scanning
calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage
capacity and biocompatibility. Suitable packaging was also selected and stability
study and aging test of the composite film were performed after packing. The
incorporation of chitosan and PEG into gelatin showed improved mechanical
properties of both TS and Eb, which suggested the occurrence of interaction among
gelatin, chitosan and PEG molecules in the composite film. The presence of
crosslinking as an interaction of above three polymers was also confirmed by FTIR
study. Results from the DSC study suggested increased thermal stability after
crosslinking. On the other hand, water uptake studies suggested excellent fluid
drainage capability and hydro-stability of the composite film. The proposed
dressing also showed excellent biocompatibility. Based on the studies related to
the performance with confirmed identity, we concluded that our developed bi-layer
film is very potential as an ideal wound dressing material.
PMID- 27612754
TI - Ibuprofen analysis in blood samples by palladium particles-impregnated sodium
montmorillonite electrodes: Validation using high performance liquid
chromatography.
AB - The electrochemical detection of ibuprofen has been studied on Palladium
Montmorillonite (Mt) modified carbon paste electrode using differential pulse
voltammetry. The optimization of the modifier preparation and the instrumental
parameters was investigated. The results indicate that ibuprofen oxidation was
favored in the presence of Pd-PdO particles. The quantitative determination of
ibuprofen was statistically analyzed and validated using HPLC method. The
detection and quantification limits, specificity and precision were found to be
acceptable. Finally, the developed method was successfully applied for ibuprofen
determination in human blood samples.
PMID- 27612755
TI - Ultrasensitive FRET-based DNA sensor using PNA/DNA hybridization.
AB - In the diagnosis of genetic diseases, rapid and highly sensitive DNA detection is
crucial. Therefore, many strategies for detecting target DNA have been developed,
including electrical, optical, and mechanical methods. Herein, a highly sensitive
FRET based sensor was developed by using PNA (Peptide Nucleic Acid) probe and QD,
in which red color QDs are hybridized with capture probes, reporter probes and
target DNAs by EDC-NHS coupling. The hybridized probe with target DNA gives off
fluorescent signal due to the energy transfer from QD to Cy5 dye in the reporter
probe. Compared to the conventional DNA sensor using DNA probes, the DNA sensor
using PNA probes shows higher FRET factor and efficiency due to the higher
reactivity between PNA and target DNA. In addition, to elicit the effect of the
distance between the donor and the acceptor, we have investigated two types of
the reporter probes having Cy5 dyes attached at the different positions of the
reporter probes. Results show that the shorter the distance between QDs and Cy5s,
the stronger the signal intensity. Furthermore, based on the fluorescence
microscopy images using microcapillary chips, the FRET signal is enhanced to be
up to 276% times stronger than the signal obtained using the cuvette by the
fluorescence spectrometer. These results suggest that the PNA probe system
conjugated with QDs can be used as ultrasensitive DNA nanosensors.
PMID- 27612756
TI - Highly porous, low elastic modulus 316L stainless steel scaffold prepared by
selective laser melting.
AB - Recently, porous metallic materials have been extensively studied as candidates
for use in the fabrication of scaffolds and augmentations to repair trabecular
bone defects, e.g. in surroundings of joint replacements. Fabricating these
complex structures by using common approaches (e.g., casting and machining) is
very challenging. Therefore, rapid prototyping techniques, such as selective
laser melting (SLM), have been investigated for these applications. In this
study, we characterized a highly porous (87 vol.%) 316L stainless steel scaffold
prepared by SLM. 316L steel was chosen because it presents a biomaterial still
widely used for fabrication of joint replacements and, from the practical point
of view, use of the same material for fabrication of an augmentation and a joint
replacement is beneficial for corrosion prevention. The results are compared to
the reported properties of two representative nonporous 316L stainless steels
prepared either by SLM or casting and subsequent hot forging. The microstructural
and mechanical properties and the surface chemical composition and interaction
with the cells were investigated. The studied material exhibited mechanical
properties that were similar to those of trabecular bone (compressive modulus of
elasticity ~0.15GPa, compressive yield strength ~3MPa) and cytocompatibility
after one day that was similar to that of wrought 316L stainless steel, which is
a commonly used biomaterial. Based on the obtained results, SLM is a suitable
method for the fabrication of porous 316L stainless steel scaffolds with highly
porous structures.
PMID- 27612757
TI - Fabrication of macroporous cement scaffolds using PEG particles: In vitro
evaluation with induced pluripotent stem cell-derived mesenchymal progenitors.
AB - Calcium phosphate cements (CPCs) have been extensively used in reconstructive
dentistry and orthopedics, but it is only recently that CPCs have been combined
with stem cells to engineer biological substitutes with enhanced healing
potential. In the present study, macroporous CPC scaffolds with defined
composition were fabricated using an easily reproduced synthesis method, with
minimal fabrication and processing steps. Scaffold pore size and porosity,
essential for cell infiltration and tissue ingrowth, were tuned by varying the
content and size of polyethylene glycol (PEG) particles, resulting in 9 groups
with different architectural features. The scaffolds were characterized for
chemical composition, porosity and mechanical properties, then tested in vitro
with human mesenchymal progenitors derived from induced pluripotent stem cells
(iPSC-MPs). Biomimetic decellularized bone scaffolds were used as reference
material in this study. Our manufacturing process resulted in the formation of
macroporous monetite scaffolds with no residual traces of PEG. The size and
content of PEG particles was found to affect scaffold porosity, and thus
mechanical properties. Irrespective of pore size and porosity, the CPC scaffolds
fabricated in this study supported adhesion and viability of human iPSC-MPs
similarly to decellularized bone scaffolds. However, the architectural features
of the scaffolds were found to affect the expression of bone specific genes,
suggesting that specific scaffold groups could be more suitable to direct human
iPSC-MPs in vitro toward an osteoblastic phenotype. Our simplistic fabrication
method allows rapid, inexpensive and reproducible construction of macroporous CPC
scaffolds with tunable architecture for potential use in dental and orthopedic
applications.
PMID- 27612758
TI - Fabrication a new modified electrochemical sensor based on Au-Pd bimetallic
nanoparticle decorated graphene for citalopram determination.
AB - This paper proposes a simple approach for sensing of citalopram (CTL) using gold
palladium bimetallic nanoparticles (Au-PdNPs) decorated graphene modified gold
electrode. Au-PdNPs were deposited at the surface of a graphene modified gold
electrode with simple electrodeposition method. The morphology and the
electrochemical properties of the modified electrode were characterized by
scanning electron microscopy (SEM), transmission electron microscopy (TEM),
atomic force microscopy (AFM), energy dispersion spectroscopy (EDS),
electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square
wave voltammetry (SWV). The novel sensor exhibited an excellent catalytic
activity towards the oxidation of CTL. The oxidation peak current of CTL, was
linear in the range of 0.5-50MUM with a detection limit 0.049MUM with respect to
concentration of citalopram. The proposed sensor was successfully applied for
determination of CTL tablet and human plasma samples with satisfactory results.
PMID- 27612759
TI - Influence of different sterilization processes on the properties of commercial
poly(lactic acid).
AB - This study aims at analyzing the modifications in the morphological, physical,
chemical and thermal properties of commercial poly(lactic acid) (PLA) films after
exposure to five different sterilization processes. Films were obtained by
compression molding, hygienized and sterilized by ethylene oxide (SEtO), hydrogen
peroxide plasma (SH2O2), saturated steam (SSS), electron beam radiation (SEB) and
gamma radiation (SGR). The samples of PLASEtO, PLASH2O2, PLASEB and PLASGR
exhibited thermal and physical changes after being submitted to sterilization
processes. PLASSS showed morphological, chemical, thermal and physical changes.
It is concluded that processes by SEtO, SH2O2, SEB and EGR can be applied for the
sterilization of PLA films and the SSS process is not recommended in view of the
data obtained and test conditions reported in this study for PLA films.
PMID- 27612760
TI - Gelatin/hydroxypropyl methylcellulose matrices - Polymer interactions approach
for oral disintegrating films.
AB - Oral disintegrating film represents an optimal alternative for delivery system of
active compounds. The choice of film-forming polymer is the first step in the
development of oral disintegrating films and the knowledge of molecular
interactions in this matrix is fundamental to advance in this area. Therefore,
this study aimed to characterize gelatin and hydroxypropyl methylcellulose (HPMC)
films and their blends as matrices of oral disintegrating films. The films were
produced by casting technique and were characterized by scanning electron
microscopy, Fourier transform infrared spectroscopy, differential scanning
calorimetry, mechanical properties, contact angle, time disintegration and
bioadhesive strength. Differential scanning calorimetry showed that enthalpy of
fusion and melting temperatures of the blends films were lower than those of the
gelatin film, which may be associated with the lack of intra-chain interactions
also observed in the Fourier transform infrared spectra. In blends, a less
compact cross-section structure was observed in scanning electron microscopy
images compared with isolated polymer films. The addition of HPMC increased the
elongation, hydrophilicity and in vitro bioadhesive force and decreased in vitro
disintegration time, important properties in the development of oral
disintegrating films. Although the mixture of the polymers showed no synergistic
behavior, this study may contribute to the development of new applications for
polymeric matrices in the pharmaceutical industry.
PMID- 27612762
TI - Electrospun composite matrices of poly(epsilon-caprolactone)-montmorillonite made
using tenside free Pickering emulsions.
AB - The production of composite electrospun matrices of poly(epsilon-caprolactone)
(PCL) using an emulsifier-free emulsion, made with minimal organic solvent, as
precursor is reported. Pickering emulsions of PCL were prepared using modified
montmorillonite (MMT) clay as the stabilizer. Hydrophobic tallow group of the
modified MMT clay resulted in analogous interaction of clay with oil and aqueous
phase and its adsorption at the interface to provide stability to the resultant
emulsion. Composite fibrous matrices of PCL and MMT were produced using
electrospinning under controlled conditions. The fiber fineness was found to
alter with PCL concentration and volume fraction of the aqueous and oil phases. A
higher tensile strength and modulus was obtained with inclusion of MMT in PCL
electrospun matrix in comparison to a matrix made using neat PCL. The presence of
clay in the fibrous matrix did not change the cell proliferation efficiency in
comparison to neat PCL matrix. Composite fibrous matrices of PCL/MMT bearing
enhanced tensile properties may find applications in areas other than tissue
engineering for example food packaging and filtration.
PMID- 27612761
TI - Synthesis and characterization of silver doped hydroxyapatite nanocomposite
coatings and evaluation of their antibacterial and corrosion resistance
properties in simulated body fluid.
AB - Silver-doped hydroxyapatite (Ca10-xAgx(PO4)6(OH)2-x) films were synthesized and
deposited on anodized titanium (Ti) using electrophoretic. The influence of
different silver-dopant contents (X=0, 0.02, 0.05, 0.08 and 0.1) on the phase
formation and microstructure of the powders were characterized by means of X-ray
diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron
spectroscope (XPS), and Fourier transform infrared spectrum analysis (FT-IR). XRD
analysis confirmed the formation of Hexagonal structure of hydroxyapatite (HAp)
annealed at 600 degrees C with a small shift in the major peak position toward
lower angles with adding silver. FT-IR spectroscopy disclosed the presence of the
different vibrational modes matching to phosphates and hydroxyl groups and the
absence of any band characteristics to silver. XPS analysis showed that 75% and
23% of silver was in the chemical states of Ag(2+) and Ag(+), respectively.
However, only about 2% of silver was in the Ag(0) state, resulting in the high
quality of nanocomposite films. The anodization treatment improves the bond
strength between the Ag doped HAp deposited layers on TiO2. HAp and silver doped
HAp (X=0.05) are regarded to be hydrophilic due to a large number of -OH groups
on the surface. The sample with content of silver (x=0.05) also showed excellent
antimicrobial efficacy (>99% reduction in viable cells). Electrochemical reveals
the passive current densities of the HAp coated anodized Ti are lower than those
of silver doped HAp coated anodized Ti, leading to a slightly lower corrosion
resistance.
PMID- 27612763
TI - Characterization of fabricated cobalt-based alloy/nano bioactive glass
composites.
AB - In this work, cobalt-based alloy/nano bioactive glass (NBG) composites with 10,
15 and 20wt% NBG were prepared and their bioactivity after immersion in simulated
body fluid (SBF) for 1 to 4weeks was studied. Scanning electron microscopy images
of two- step sintered composites revealed relatively dense microstructure. The
results showed that density of composite samples decreased with increase in NBG
amount. The microstructure analysis as well as energy dispersive X-ray analysis
(EDX) revealed that small amount of calcium phosphate phases precipitates on the
surface of composite samples after 1week immersion in SBF. After 2weeks
immersion, considerable amounts of cauliflower-like shaped precipitations were
seen on the surface of the composites. Based on EDX analysis, these
precipitations were composed mainly from Ca, P and Si. The observed bands in the
Fourier transform infrared spectroscopy of immersed composites samples for 4weeks
in SBF, were characteristic bands of hydroxyapatite. Therefore it is possible to
form hydroxyapatite layer on the surface of composite samples during immersion in
SBF. The results indicated that prepared composites unlike cobalt-based alloy are
bioactive, promising their possibility for implant applications.
PMID- 27612764
TI - Bioconductive 3D nano-composite constructs with tunable elasticity to initiate
stem cell growth and induce bone mineralization.
AB - Bioactive 3D composites play an important role in advanced biomaterial design to
provide molecular coupling and improve integrity with the cellular environment of
the native bone. In the present study, a hybrid lyophilized polymer composite
blend of anionic charged sodium salt of carboxymethyl chitin and gelatin (CMChNa
GEL) reinforced with nano-rod agglomerated hydroxyapatite (nHA) has been
developed with enhanced biocompatibility and tunable elasticity. The scaffolds
have an open, uniform and interconnected porous structure with an average pore
diameter of 157+/-30MUm and 89.47+0.03% with four dimensional X-ray. The aspect
ratio of ellipsoidal pores decrease from 4.4 to 1.2 with increase in gelatin
concentration; and from 2.14 to 1.93 with decrease in gelling temperature. The
samples were resilient with elastic stain at 1.2MPa of stress also decreased from
0.33 to 0.23 with increase in gelatin concentration. The crosslinker HMDI
(hexamethylene diisocyanate) yielded more resilient samples at 1.2MPa in
comparison to glutaraldehyde. Increased crosslinking time from 2 to 4h in
continuous compression cycle show no improvement in maximum elastic stain of
1.2MPa stress. This surface elasticity of the scaffold enables the capacity of
these materials for adherent self renewal and cultivation of the NTERA-2 cL.D1
(NT2/D1), pluripotent embryonal carcinoma cell with biomechanical surface, as is
shown here. Proliferation with MG-63, ALP activity and Alizarin red
mineralization assay on optimized scaffold demonstrated ***p<0.001 between
different time points thus showing its potential for bone healing. In pre
clinical study histological bone response of the scaffold construct displayed
improved activity of bone regeneration in comparison to self healing of control
groups (sham) up to week 07 after implantation in rabbit tibia critical-size
defect. Therefore, this nHA-CMChNa-GEL scaffold composite exhibits inherent and
efficient physicochemical, mechanical and biological characteristics based on gel
concentrations, gelatin mixing and gelling temperature thus points to creating
bioactive 3D scaffolds with tunable elasticity for orthopedic applications.
PMID- 27612765
TI - Comparison between all-on-four and all-on-six treatment concepts and framework
material on stress distribution in atrophic maxilla: A prototyping guided 3D-FEA
study.
AB - We evaluated two treatment concepts for the rehabilitation of moderate atrophic
maxilla with dental implants (all-on-four and all-on-six) and the effect of
framework material on the stress distribution of implant-support system. A three
dimensional finite element model based on a prototype was built to simulate an
entirely edentulous maxilla with moderate sinus pneumatization that was
rehabilitated with a full-arch fixed dental prosthesis. Four standard implants
were positioned according to the all-on-four concept and four standard implants
and two short implants were placed according to the all-on-six concept. Three
framework materials were evaluated: cobalt-chrome (CoCr), titanium (Ti) and
zirconia (Zr), totalizing six groups. A unilateral oblique force of 150N was
applied to the posterior teeth. The von Mises (sigmaVM), maximum (sigmamax) and
minimum (sigmamin) principal stress and displacements were obtained. All-on-six
showed smaller sigmamin, sigmaVM and sigmamax values on the cortical bone,
implants and trabecular bone, respectively. All-on-four exhibited higher
displacement levels. Ti presented the highest stress values on the cortical bone,
implants, abutments, prosthetic screws and displacement levels. In conclusion,
the all-on-six approach and framework stiffer materials showed the most favorable
biomechanical behavior. However, the stress values did not exceed the bone
resistance limits for both treatment concepts.
PMID- 27612766
TI - A simple green route to obtain poly(vinyl alcohol) electrospun mats with improved
water stability for use as potential carriers of drugs.
AB - Poly(vinyl alcohol) (PVA) is a hydrophilic, biocompatible and nontoxic polymer.
However, because of its low water-resistance, some applications for PVA-based
materials are limited (e.g., drug delivery systems and wound dressings). In the
current work, PVA mats containing tetracycline hydrochloride (TC) were
successfully developed by electrospinning. In order to improve the water
stability of the systems, the cross-linking of the PVA matrix was induced by
citric acid (CA) addition together with heating treatments (150 degrees C or 190
degrees C for 3min). TC presence led to a strong increase in the electrical
conductivity of the blends and as a result, fibers with about 44% lower diameter
(270nm) than that of the corresponding unloaded mats (485nm) were obtained. Laser
scanning confocal microscopy images indicated that TC was well distributed along
the PVA nanofibers. The mats were evaluated by FTIR, which revealed chemical
interactions between PVA hydroxyl groups and CA carboxylic ones. The treatment at
150 degrees C for 3min proved to be the more suitable for the preparation of TC
containing mats with improved water resistance, maintaining the TC antimicrobial
activity against both Escherichia coli and Staphylococcus aureus almost
unaltered. These mats showed a burst release of TC, giving around 95% of the drug
within the first hour of immersion in water.
PMID- 27612767
TI - Fabrication and characterization of carboxymethyl cellulose novel microparticles
for bone tissue engineering.
AB - In this study we developed carboxymethyl cellulose (CMC) microparticles through
ionic crosslinking with the aqueous ion complex of zirconium (Zr) and further
complexing with chitosan (CS) and determined the physio-chemical and biological
properties of these novel microparticles. In order to assess the role of Zr,
microparticles were prepared in 5% and 10% (w/v) zirconium tetrachloride
solution. Scanning electron microscopy (SEM) with energy dispersive X-ray
spectrometer (EDS) results showed that Zr was uniformly distributed on the
surface of the microparticles as a result of which uniform groovy surface was
obtained. We found that Zr enhances the surface roughness of the microparticles
and stability studies showed that it also increases the stability of
microparticles in phosphate buffered saline. The crosslinking of anionic CMC with
cationic Zr and CS was confirmed by Fourier transform infrared spectroscopy
(FTIR) results. The response of murine pre-osteoblasts (OB-6) when cultured with
microparticles was investigated. Live/dead cell assay showed that microparticles
did not induce any cytotoxic effects as cells were attaching and proliferating on
the well plate as well as along the surface of microparticles. In addition, SEM
images showed that microparticles support the attachment of cells and they
appeared to be directly interacting with the surface of microparticle. Within
10days of culture most of the top surface of microparticles was covered with a
layer of cells indicating that they were proliferating well throughout the
surface of microparticles. We observed that Zr enhances the cell attachment and
proliferation as more cells were present on microparticles with 10% Zr. These
promising results show the potential applications of CMC-Zr microparticles in
bone tissue engineering.
PMID- 27612768
TI - Inhibition of Staphylococcus aureus biofilm by a copper-bearing 317L-Cu stainless
steel and its corrosion resistance.
AB - The present study investigated the antibacterial performance, corrosion
resistance and surface properties of antibacterial austenitic 317L-Cu stainless
steel (317L-Cu SS). After 4.5wt% copper was added to 317L stainless steel (317L
SS), the new alloy underwent solid solution and aging heat treatment. Fluorescent
staining using 4',6-diamidino-2-phenylindole (DAPI) revealed that the 317L-Cu SS
showed strong antibacterial efficacy, achieving a 99% inhibition rate of sessile
Staphylococcus aureus cells after 5days. The corrosion data obtained by
potentiodynamic polarization curves indicated that in comparison with 317L SS,
the pitting potential and corrosion current density of 317L-Cu slightly decreased
due to the addition of Cu. The 317L-Cu SS exhibited no cytotoxicity against
zebrafish (Danio rerio) embryos. The experimental results in this study
demonstrated that the new alloy has potential applications in medical and daily
uses.
PMID- 27612770
TI - Effect of extrusion processing on the microstructure, mechanical properties,
biocorrosion properties and antibacterial properties of Ti-Cu sintered alloys.
AB - Ti-Cu sintered alloys, Ti-Cu(S) alloy, have exhibited good anticorrosion
resistance and strong antibacterial properties, but low ductility in previous
study. In this paper, Ti-Cu(S) alloys were subjected to extrusion processing in
order to improve the comprehensive property. The phase constitute,
microstructure, mechanical property, biocorrosion property and antibacterial
activity of the extruded alloys, Ti-Cu(E), were investigated in comparison with
Ti-Cu(S) by X-ray diffraction (XRD), optical microscopy (OM), scanning electronic
microscopy (SEM) with energy disperse spectroscopy (EDS), mechanical testing,
electrochemical testing and plate-count method in order to reveal the effect of
the extrusion process. XRD, OM and SEM results showed that the extrusion process
did not change the phase constitute but refined the grain size and Ti2Cu particle
significantly. Ti-Cu(E) alloys exhibited higher hardness and compressive yield
strength than Ti-Cu(S) alloys due to the fine grain and Ti2Cu particles. With the
consideration of the total compressive strain, it was suggested that the
extrusion process could improve the ductility of Ti-Cu alloy(S) alloys.
Electrochemical results have indicated that the extrusion process improved the
corrosion resistance of Ti-Cu(S) alloys. Plate-count method displayed that both
Ti-Cu(S) and Ti-Cu(E) exhibited strong antibacterial activity (>99%) against S.
aureus. All these results demonstrated that hot forming processing, such as the
extrusion in this study, refined the microstructure and densified the alloy, in
turn improved the ductility and strength as well as anticorrosion properties
without reduction in antibacterial properties.
PMID- 27612769
TI - Biological responses of diamond-like carbon (DLC) films with different structures
in biomedical application.
AB - Diamond-like carbon (DLC) films are potential candidates for artificial joint
surface modification in biomedical applications, and the influence of the
structural features of DLC surfaces on cell functions has attracted attention in
recent decades. Here, the biocompatibility of DLC films with different structures
was investigated using macrophages, osteoblasts and fibroblasts. The results
showed that DLC films with a low ratio of sp(2)/sp(3), which tend to have a
structure similar to that of diamond, led to less inflammatory, excellent
osteogenic and fibroblastic reactions, with higher cell viability, better
morphology, lower release of TNF-alpha (tumor necrosis factor-alpha) and IL-6
(interleukin-6), and higher release of IL-10 (interleukin-10). The results also
demonstrated that the high-density diamond structure (low ratio of sp(2)/sp(3))
of DLC films is beneficial for cell adhesion and growth because of better protein
adsorption without electrostatic repulsion. These findings provide valuable
insights into the mechanisms underlying inhibition of an inflammatory response
and the promotion of osteoblastogenesis and fibrous propagation, and effectively
build a system for evaluating the biocompatibility of DLC films.
PMID- 27612771
TI - An enzyme free Vitamin C augmented sensing with different ZnO morphologies on
SnO2/F transparent glass electrode: A comparative study.
AB - Three types of Zinc oxide (ZnO) nanostructures viz. ZnO nanocrystals (ZnONCs),
ZnO nanoparticles (ZnONPs) and ZnO nanobelts (ZnONBs) were synthesized and
characterized by UV-Vis, FTIR and SEM. A comparison of signal amplification by
these ZnO nanostructures as judged by cyclic voltammetry (CV), electrochemical
impedance spectroscopy (EIS) and Linear Sweep Voltammetry (LSV) revealed that
ZnONCs are better sensing interface for electrochemical detection. When these ZnO
nanostructure were compared electrochemically for sensing Vitamin C, ZnONC's
sensor outperformed the ZnONP and ZnONB sensor and previously reported sensors.
The ZnONCs/MB/FTO electrode showed a wide linear sensing range (0.001MUM to
4000MUM), low detection limit (0.0001MUM), a small response time (5s) and a
storage stability of 6months. To the best of our knowledge, this elevated
sensitivity and remarkable stability for electrochemical Vitamin C detection
using ZnONC's have not been reported so far.
PMID- 27612772
TI - Development of PLGA-coated beta-TCP scaffolds containing VEGF for bone tissue
engineering.
AB - Bone tissue engineering is sought to apply strategies for bone defects healing
without limitations and short-comings of using either bone autografts or
allografts and xenografts. The aim of this study was to fabricate a thin layer
poly(lactic-co-glycolic) acid (PLGA) coated beta-tricalcium phosphate (beta-TCP)
scaffold with sustained release of vascular endothelial growth factor (VEGF).
PLGA coating increased compressive strength of the beta-TCP scaffolds
significantly. For in vitro evaluations, canine mesenchymal stem cells (cMSCs)
and canine endothelial progenitor cells (cEPCs) were isolated and characterized.
Cell proliferation and attachment were demonstrated and the rate of cells
proliferation on the VEGF released scaffold was significantly more than compared
to the scaffolds with no VEGF loading. A significant increase in expression of
COL1 and RUNX2 was indicated in the scaffolds loaded with VEGF and MSCs compared
to the other groups. Consequently, PLGA coated beta-TCP scaffold with sustained
and localized release of VEGF showed favourable results for bone regeneration in
vitro, and this scaffold has the potential to use as a drug delivery device in
the future.
PMID- 27612773
TI - Formulation and optimization of niosomes for topical diacerein delivery using 3
factor, 3-level Box-Behnken design for the management of psoriasis.
AB - This research aimed towards the design of preparations of diacerein loaded
cholesterol rich niosomes by employing a 3-factor, 3-level Box-Behnken design.
Results indicated that Span 60 (90mg) and cholesterol (10mg), and 45min of
hydration time were found to be optimum for niosomes preparation. The prepared
cholesterol rich niosomes were uniform and spherical in size. Optimized
formulation F2 entrapped the drug with 83.02% efficiency in the cholesterol rich
niosomes of the size 477.8nm, presented the flux of 2.820MUg/cm(2)/h, followed
Higuchi model and non Fickian transport mechanism. The confocal laser scanning
microscopy showed that niosomes accentuated the penetration of diacerein in the
epidermal and dermal layer of rat skin. Stability study confirmed that
cholesterol rich niosomes were stable for 2months at 4 degrees C. Concisely, the
results showed that targeted diacerein delivery might be achieved using topically
applied niosomes for enhanced treatment of psoriasis, which might eliminate
adverse side effects associated with systemic exposure.
PMID- 27612774
TI - The influence mechanism of processing holes on the flexural properties of
biomimetic integrated honeycomb plates.
AB - The influence mechanism of processing holes on the flexural properties of fully
integrated honeycomb plates (FIHPs) was analyzed using the finite element method
(FEM), and the results were compared with experimental data, yielding the
following findings: 1) Processing holes under tensile stress have a significant
impact on the mechanical properties of FIHPs, which is particularly obvious when
initial imperfections are formed during sample preparation. 2) A proposed design
technique based on changing the shape of the processing holes from circular to
elliptical effectively reduces the stress concentration when such holes must
exist in skin or components under tension, and this method motivates a design
concept for experimental tests of FIHPs bearing dynamic or fatigue loads. 3) The
flexural failure modes of FIHPs were confirmed via FEM analysis, and the
mechanism by which trabeculae in FIHPs can effectively prevent cracks from
emerging and cause cracks to develop along certain paths was ascertained.
Therefore, this paper provides a theoretical basis for the design of processing
holes in bionic honeycomb plates and other similar components in practical
engineering applications.
PMID- 27612775
TI - Thermoresponsive polyurethane/siloxane membrane for wound dressing and cell sheet
transplantation: In-vitro and in-vivo studies.
AB - Polyurethane/siloxane based wound dressing for transferring fibroblast cell sheet
to wounded skin and ability to provide an optimum condition for cellular activity
at damaged tissue was prepared in this research. The dressing was made
thermoresponsive, via the introduction of a poly(N-isopropyl acrylamide)
copolymer into the backbone of dressing. The ability of membrane for adhesion,
growth, and proliferation of fibroblast cells was improved via surface
modification with gelatin. The optimized dressing exhibited appropriate tensile
strength (4.5MPa) and elongation at break (80%) to protect wound against physical
forces. Due to controlled equilibrium water absorption of about 89% and water
vapor transmission rate of 2040g/m(2)day, the dressing could maintain the
favorable moist environment over moderate to high exuding wounds. The grown cell
sheet on dressing membrane could easily roll up from the surface just with
lowering the temperature. The in vivo study of the wound dressed with cell loaded
membrane confirmed the accelerated healing and production of tissue with complete
re-epithelization, enhanced vascularization, and increased collagen deposition on
the damaged area.
PMID- 27612776
TI - Modeling of boldine alkaloid adsorption onto pure and propyl-sulfonic acid
modified mesoporous silicas. A comparative study.
AB - The present study deals with the adsorption of boldine onto pure and propyl
sulfonic acid-functionalized SBA-15, SBA-16 and mesocellular foam (MCF)
materials. Siliceous adsorbents were characterized by nitrogen sorption analysis,
transmission electron microscopy (TEM), scanning electron microscopy (SEM),
Fourier-transform infrared (FT-IR) spectroscopy and thermogravimetric analysis.
The equilibrium adsorption data were analyzed using the Langmuir, Freundlich,
Redlich-Peterson, and Temkin isotherms. Moreover, the Dubinin-Radushkevich and
Dubinin-Astakhov isotherm models based on the Polanyi adsorption potential were
employed. The latter was calculated using two alternative formulas including
solubility-normalized (S-model) and empirical C-model. In order to find the best
fit isotherm, both linear regression and nonlinear fitting analysis were carried
out. The Dubinin-Astakhov (S-model) isotherm revealed the best fit to the
experimental points for adsorption of boldine onto pure mesoporous materials
using both linear and nonlinear fitting analysis. Meanwhile, the process of
boldine sorption onto modified silicas was described the best by the Langmuir and
Temkin isotherms using linear regression and nonlinear fitting analysis,
respectively. The values of adsorption energy (below 8kJ/mol) indicate the
physical nature of boldine adsorption onto unmodified silicas whereas the ionic
interactions seem to be the main force of alkaloid adsorption onto functionalized
sorbents (energy of adsorption above 8kJ/mol).
PMID- 27612777
TI - Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell
culture model, controlled release and stability.
AB - There is an ongoing demand for new approaches for treating localized bone
pathologies. Here we propose a new strategy for treatment of such conditions, via
local delivery of hormones/drugs to the trauma site using drug releasing nano
engineered implants. The proposed implants were prepared in the form of small Ti
wires/needles with a nano-engineered oxide layer composed of array of titania
nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix
containing human osteoblast-like, and the results confirmed cell migration onto
the implants and their attachment and spread. To investigate therapeutic
efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved
anabolic therapeutic for the treatment of severe bone fractures, were inserted
into 3D gels containing osteoblast-like cells. Gene expression studies revealed a
suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of
nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH
from TNTs at concentrations sufficient to alter cell function. The performance of
the TNTs wire implants using an example of a drug needed at relatively higher
concentrations, the anti-inflammatory drug indomethacin, is also demonstrated.
Finally, the mechanical stability of the prepared implants was tested by their
insertion into bovine trabecular bone cores ex vivo followed by retrieval, which
confirmed the robustness of the TNT structures. This study provides proof of
principle for the suitability of the TNT/Ti wire implants for localized bone
therapy, which can be customized to cater for specific therapeutic requirements.
PMID- 27612778
TI - Evaluation of mechanical and morphologic features of PLLA membranes as supports
for perfusion cells culture systems.
AB - Porous biodegradable PLLA membranes, which can be used as supports for perfusion
cell culture systems were designed, developed and characterized. PLLA membranes
were prepared via diffusion induced phase separation (DIPS). A glass slab was
coated with a binary PLLA-dioxane solution (8wt.% PLLA) via dip coating, then
pool immersed in two subsequent coagulation baths, and finally dried in a
humidity-controlled environment. Surface and mechanical properties were evaluated
by measuring pore size, porosity via scanning electron microscopy, storage
modulus, loss modulus and loss angle by using a dynamic mechanical analysis
(DMA). Cell adhesion assays on different membrane surfaces were also performed by
using a standard count method. Results provide new insights into the foaming
methods for producing polymeric membranes and supply indications on how to
optimise the fabrication parameters to design membranes for tissue cultures and
regeneration.
PMID- 27612779
TI - Influence of Eu(3+) doping content on antioxidant properties of Lu2O3 sol-gel
derived nanoparticles.
AB - This paper presents the synthesis of pure and europium-doped lutetium oxide
(Lu2O3) powders prepared by sol-gel method. The influence of europium ion
concentration into Lu2O3 nanocrystallites was investigated for first time in an
in vitro system using a modified ABTS radical cation decolorization assay to
determine the antioxidant activity. The crystalline structure of Lu2O3 and
Eu:Lu2O3 powders was elucidated by XRD obtaining cubic phase in all system
without secondary products in accordance with FT-IR results. By TEM and Scherrer
equation, it was determined that Lu2O3 and Eu:Lu2O3 powders presented nearly
spherical particle morphology with crystallites sizes in the range of 8 to 13nm.
The antioxidant assays results revealed that europium ion enhance Lu2O3 powders
antioxidant properties, showing that 12.5mol% of europium is sufficient to reach
its maximum capacity.
PMID- 27612780
TI - Ceramic scaffolds enriched with gentamicin loaded poly(lactide-co-glycolide)
microparticles for prevention and treatment of bone tissue infections.
AB - Bone scaffolds are susceptible for bacterial infection when implanted,
particularly in compromised bone. Therefore anti-bacterial bone scaffolds are
desirable. Here a novel approach to provide bactericidal properties for titanium
dioxide scaffolds is proposed. Gentamicin loaded poly(L-lactide-co-glycolide)
microparticles were immobilized on the scaffold pore walls by sodium alginate
hydrogel. The results show that the microparticles were effectively immobilized
on the scaffolds. Desired burst release was observed within the first 8h and
gentamicin dose reached 125MUg from single scaffold that corresponded to ~25% of
total drug introduced in the system. Following the initial burst, the dose was
gradually decreasing up to day 10 and afterwards a sustained release of 3MUg/day
was measured. Cumulatively ~90% of the drug was delivered up to day 50. Above
pattern, i.e. burst release with following sustained release, is desired for
prevention of perioperative bone infections: burst release stops local infections
during post-implantation "decisive period" while further sustained drug release
prevents bacterial recolonization. In vitro studies confirmed antimicrobial
activity of released gentamicin against Staphylococcus spp. and cytocompatibility
of the system with osteoblast-like cells (MG-63). Thus the system is a viable
option for the treatment of bone tissue defects.
PMID- 27612781
TI - Tuning the conductivity and inner structure of electrospun fibers to promote
cardiomyocyte elongation and synchronous beating.
AB - The key to addressing the challenges facing cardiac tissue engineering is the
integration of physical, chemical, and electrical cues into scaffolds. Aligned
and conductive scaffolds have been fabricated as synthetic microenvironments to
improve the function of cardiomyocytes. However, up to now, the influence of
conductive capability and inner structure of fibrous scaffolds have not been
determined on the cardiomyocyte morphologies and beating patterns. In the current
study, highly aligned fibers were fabricated with loaded up to 6% of carbon
nanotubes (CNTs) to modulate the electrical conductivity, while blend and coaxial
electrospinning were utilized to create a bulk distribution of CNTs in fiber
matrices and a spatial embedment in fiber cores, respectively. Conductive
networks were formed in the fibrous scaffolds after the inoculation of over 3%
CNTs, and the increase in the conductivity could maintain the cell viabilities,
induce the cell elongation, enhance the production of sarcomeric alpha-actinin
and troponin I, and promote the synchronous beating of cardiomyocytes. Although
the conductivity of blend fibers is slightly higher than that of coaxial fibers
with the same CNT loadings, the lower exposures to CNTs resulted in higher cell
viability, elongation, extracellular matrix secretion and beating rates for
cardiomyocytes on coaxial fibers. Taken altogether, core-sheath fibers with
loaded 5% of CNTs in the fiber cores facilitated the cardiomyocyte growth with a
production of organized contractile proteins and a pulsation frequency close to
that of the atrium. It is suggested that electrospun scaffolds that couple
conductivity and fibrous structure considerations may provide optimal stimuli to
foster cell morphology and functions for myocardial regeneration or establishment
of in vitro cardiomyocyte culture platform for drug screening.
PMID- 27612782
TI - Synthesis of calcium hydrogen phosphate and hydroxyapatite coating on SS316
substrate through pulsed electrodeposition.
AB - The orthopaedic implants for human body are generally made of different
biomaterials like stainless steels or Ti based alloys. However, it has been found
that from surface properties point of view, none of these materials is attractive
for fast tissue or cell growth on the surface of implant. This is one of the most
important criteria to assure quick bonding between implant and body tissues vis-a
vis minimum recovery time for the patient. Keeping in view of the above facts,
this work involves the pulsed electro-deposition coating of biocompatible
hydroxyapatite and its group compounds from a diluted bath of calcium and
phosphate salt at various current densities over the biomaterial sheet of SS316.
SEM study confirms different morphologies of the coatings at different current
densities. Characterization techniques like X-ray diffraction, SEM with EDX and
FTIR have been used to confirm the phase and percentage quantity of
hydroxyapatite compound in the depositions. This coating can serve as a medium
for faster tissue growth over the metallic implants.
PMID- 27612783
TI - Efficacy of silver coated surgical sutures on bacterial contamination, cellular
response and wound healing.
AB - The resistance demonstrated by many microorganisms towards conventional
antibiotics has stimulated the interest in alternative antimicrobial agents and
in novel approaches for prevention of infections. Silver, a natural braod
spectrum antimicrobial agent known since antiquity, has been widely employed in
biomedical field due to its recognized antibacterial, antifungal and antiviral
properties. In this work, antibacterial silver coatings were deposited on
absorbable surgical sutures through the in situ photo-chemical deposition of
silver clusters. Scanning electron microscopy (SEM), Energy dispersive X-ray
spectroscopy (EDX) and thermo-gravimetric analysis (TGA) were performed in order
to investigate the presence and distribution of the silver clusters on the
substrate. The amounts of silver deposited and released by the silver treated
sutures were calculated through Inductively Coupled Plasma-Mass Spectroscopy (ICP
MS), and the results were related to the biodegradation of the material. The
microbiological properties and the potential cytotoxicity of the silver-treated
sutures were investigated in relation with hydrolysis experiments, in order to
determine the effect of the degradation on antibacterial properties and
biocompatibility.
PMID- 27612784
TI - Fabrication and evaluation of novel zeolite membranes to control the neoplastic
activity and anti-tumoral drug treatments in human breast cancer cells. Part 1:
Synthesis and characterization of Pure Zeolite Membranes and Mixed Matrix
Membranes for adhesion and growth of cancer cells.
AB - Novel pure and hybrid zeolite membranes were prepared with appropriate different
physicochemical characteristics such as frameworks, hydrophilicity, crystal size,
chemical composition, acid-base properties (Point of Zero Charge, PZC) and
surface morphology and used in inorganic cell/scaffold constructs. Because the
control of cell interactions, as the adhesion, proliferation, remodelling and
mobility, is important for differentiation and progression of tumors, this work
focused on response of cancer cells adhered and grown on synthesized zeolite
surfaces in order to study the influence of these scaffolds in controlled
conditions. We have selected the MCF-7 and MDA-MB-231 human breast cancer cell
line as model tumor cell lines. This study showed that all the zeolite membranes
synthesized are excellent scaffolds because they are very selective materials to
support the adhesion and growth of neoplastic cells. All zeolite scaffolds were
characterized by FESEM, FTIR ATR, XRD, AFM, PZC and contact angle analyses. Cell
adhesion, viability and morphology were measured by count, MTT assay and FESEM
microphotography analysis, at various incubation times.
PMID- 27612785
TI - Physicochemical characterization of three fiber-reinforced epoxide-based
composites for dental applications.
AB - Fiber-reinforced composite (FRC) biomedical materials are in contact with living
tissues arising biocompatibility questions regarding their chemical composition.
The hazards of materials such as Bisphenol A (BPA), phthalate and other monomers
and composites present in FRC have been rationalized due to its potential
toxicity since its detection in food, blood, and saliva. This study characterized
the physicochemical properties and degradation profiles of three different
epoxide-based materials intended for restorative dental applications.
Characterization was accomplished by several methods including FTIR, Raman,
Brunauer-Emmett-Teller (BET) Analysis, X-ray fluorescence spectroscopy, and
degradation experiments. Physicochemical characterization revealed that although
materials presented similar chemical composition, variations between them were
more largely accounted by the different phase distribution than chemical
composition.
PMID- 27612786
TI - Blue photoluminescent carbon nanodots from limeade.
AB - Carbon-based photoluminescent nanodot has currently been one of the promising
materials for various applications. The remaining challenges are the carbon
sources and the simple synthetic processes that enhance the quantum yield,
photostability and biocompatibility of the nanodots. In this work, the synthesis
of blue photoluminescent carbon nanodots from limeade via a single-step
hydrothermal carbonization process is presented. Lime carbon nanodot (L-CnD),
whose the quantum yield exceeding 50% for the 490nm emission in gram-scale
amounts, has the structure of graphene core functionalized with the oxygen
functional groups. The micron-sized flake of the as-prepared L-CnD powder
exhibits multicolor emission depending on an excitation wavelength. The L-CnDs
are demonstrated for rapidly ferric-ion (Fe(3+)) detection in water compared to
Fe(2+), Cu(2+), Co(2+), Zn(2+), Mn(2+) and Ni(2+) ions. The photoluminescence
quenching of L-CnD solution under UV light is used to distinguish the Fe(3+) ions
from others by naked eyes as low concentration as 100MUM. Additionally, L-CnDs
provide exceptional photostability and biocompatibility for imaging yeast cell
morphology. Changes in morphology of living yeast cells, i.e. cell shape
variation, and budding, can be observed in a minute-period until more than an
hour without the photoluminescent intensity loss.
PMID- 27612787
TI - Multifunctional soft hybrid bio-platforms based on nano-silver and natural
compounds.
AB - Novel nanohybrids consisting of nano-Ag, chitosan, lipids and phyto-compounds
(chlorophyll a and curcumin) have been achieved through a simple bottom-up
strategy, resulting in stable (ZP=-30.9mV) and spherical-shaped nano-entities
with size <200nm (estimated by AFM analysis and DLS measurements). The formation
of these biohybrids was monitored by absorption and emission spectroscopy,
exploiting the spectral fingerprint of chlorophyll a. The bio-performances of
these hybrid materials such as: high antioxidant activity (96.63%), strong
biocidal properties against Escherichia coli ATCC 8738 (exhibiting an inhibition
zone diameter of 32mm), hemocompatibility, in vitro cytotoxicity against HT-29
cancer cells and no toxicity to normal cells (in the biohybrid concentration
range of 5.7-17%), make them promising candidates in bio-applications
(antimicrobial and antioxidant coating, cancer treatment).
PMID- 27612788
TI - Non-hollow-core Cybister trabeculae and compressive properties of two biomimetic
models of beetle forewings.
AB - In 2006, the forewing trabeculae of Cybister tripunctatus Olivier (i.e.,
Cybister) beetles were reported to be hollow, and a biomimetic structural model
(i.e., Song's model) was reported to exhibit better compressive mechanical
properties than a solid-core trabecula-honeycomb model (i.e., Chen's model). To
test these assertions, the current study first observed the trabecular
microstructure of the Cybister beetle and confirmed that the trabeculae are
solid. Second, the finite element method (FEM) was used to perform a contrast
analysis of the compressive mechanical properties of Song's and Chen's biomimetic
models. The results indicated that Chen's model exhibited better compressive
mechanical properties. These findings, which are completely opposite of Song's
findings, were obtained because the comparison models designed for use in Song's
study were not comparable to that of Chen's model in terms of the core volumes.
This study will benefit the development of beetle forewing biomimetic research.
PMID- 27612789
TI - A novel suture retention test for scaffold strength characterization in
ophthalmology.
AB - Sutures are a common way to attach scaffolds in patients. For tubular cardiac
scaffolds, the 'suture retention strength' is commonly used to evaluate the
resistance of a scaffold against the pull-out of a suture. In order to make this
quantity accessible for ophthalmological scaffolds the test procedure has been
modified in a novel way. Polycaprolactone (PCL) films of different thicknesses
and an amniotic membrane (AM) were used for the experiments. Circular samples
with a radius of 7mm were taken and a suture was passed through each sample and
tied to a loop. The sample was clamped in a tensile tester and a bolt was passed
through the loop. The suture was then pulled with a constant deformation rate
until pull-out occurred. The suture retention strength, the deformation at the
suture retention strength, and the deformation at rupture were determined for
each sample. The presented modified suture retention test allows to measure the
relevant parameters of samples on the scale of ophthalmological scaffolds in a
reproducible way. A comparison between the first data on PCL and AM has been
made.
PMID- 27612790
TI - Preparation and characterization of soy protein films with a durable water
resistance-adjustable and antimicrobial surface.
AB - A water resistant surface was first obtained by immobilizing hydrophobic
copolymers, poly (styrene-co-glycidyl methacrylate) (PSG), with functional groups
on soy protein isolate (SPI) films. XPS and AFM results showed that PSG
copolymers were immobilized on the film by chemical bonding, and formed a rough
surface with some bumps because of the segregation of two different phases on PSG
copolymers. Water resistance of the modified films could be adjusted dramatically
by further immobilizing different amounts of guanidine-based antimicrobial
polymers, poly (hexamethylene guanidine hydrochloride) (PHMG) on the resulting
hydrophobic surface. The introduction of hydrophilic PHMG on the resulting
surface generated many micropores, which potentially increased the water uptake
of the modified films. Furthermore, the modified SPI films showed higher
thermostability compared to native SPI film and broad-spectrum antimicrobial
activity by contact killing, attributed to the presence of PHMG on the surface.
The modified SPI film with a multi-functional surface showed potential for
applications in the packaging and medical fields.
PMID- 27612791
TI - Optical and biological properties of transparent nanocrystalline hydroxyapatite
obtained through spark plasma sintering.
AB - Transparent bioceramics have attracted a large amount of research interest as
they facilitate direct observation of biointerfacial reactions. Thus far,
attempts to achieve transparent hydroxyapatite have been focused on augmenting
the sintering pressure and/or extending the sintering duration. This study aims
at fabricating transparent HA using a direct and fast spark plasma sintering
process with appropriate starting powder and moderate sintering pressure. Three
types of raw powder, namely micro-spheres, nano-rods and nano-spheres, were
sintered to investigate the optical and biological properties of the compacted
pellets. It was found that in terms of transparency, the micro-sphere pellet
sintered at 1000 degrees C stood out with an in-line transmittance as high as 84%
achieved at 1300nm for a 2mm thick sample. In addition, pellets fabricated from
micro-spheres demonstrated the highest cell viability in in vitro biological
tests with L929 cells. Living cells cultured on a transparent micro-sphere pellet
could be directly and clearly observed by light microscopy. It is thus concluded
that the micro-sphere powder is the most desirable raw material to manufacture
transparent hydroxyapatite because it could enable dense pellets with notably
high transparency and outstanding in vitro biocompatibility to be readily
obtained.
PMID- 27612792
TI - Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their
enhanced antihyperlipidemic activity.
AB - The objective of this study was to demonstrate the therapeutic as well as
biopolymer like characteristics of naturally occurring sericin protein for
development of nanoparticulate system of atorvastatin (Atr) to improve
therapeutic effect and to reduce toxicity. The sericin encapsulated atorvastatin
nanoparticles (Seri-Atr NPs) were prepared by desolvation method utilizing
genipin (Gn) as a natural and nontoxic crosslinker. The optimized NPs exhibited
small particle size (166+/-0.30nm), high entrapment efficiency (91+/-0.69%) and
uniform spherical shape with sustained release profile. Moreover, the results of
pharmacokinetic studies indicated an increase in AUC0-infinity of NPs (1189.74+/
52.3hng/ml) compared with Atr (501.84+/-66hng/ml). The cellular uptake of NPs
suggested an interaction of negatively charged particles with the cell surface
and considerable reduction in systemic toxicity. Histopathology studies also
demonstrated the therapeutic potential of sericin and cytocompatibility. Hence,
genipin crosslinked sericin based nanoparticles represents a promising
nanoplatform for improved therapeutic efficiency of Atr.
PMID- 27612793
TI - Mechanical and antibacterial properties of a nanocellulose-polypyrrole multilayer
composite.
AB - In this study, a composite film based on TEMPO-oxidized cellulose nanofibers
(TOCN), polyvinyl alcohol (PVA) and polypyrrole (PPy) was synthesized in situ by
a chemical polymerization, resulting in the induced absorption of PPy on the
surface of the TOCN. The composite films were investigated with scanning electron
microscopy, thermogravimetric analysis, contact angle measurements, mechanical
tests, and evaluation of antibacterial properties. The developed composite has
nearly identical Young modulus (3.4GPa), elongation (2.6%) and tensile stress
(about 51MPa) to TOCN even if PPy, which as poor properties by itself, was
incorporated. From the energy-dispersive X-ray spectroscopy (EDX) results, it was
shown that PPy is mainly located on the composite surface. Results confirmed by
an increase from 54.5 to 83 degrees in contact angle, an increased heat
protection (Thermogravimetric analysis) and a decrease in surface energy. The
nanocomposites were also evaluated for antibacterial activity against bacteria
occasionally found in food: Gram-positive Bacillus subtilis (B. subtilis) and
Gram-negative bacteria Escherichia coli (E. coli). The results indicate that the
nanocomposites are effective against all of the bacteria studied as shown by the
decrease of 5.2logcolonyformingunits (CFU) for B. subtilis and 6.5logCFU for E.
coli. Resulting in the total destruction of the studied bacteria. The perfect
match between the resulting inhibition zone and the composite surface area has
demonstrated that our composite was contact active with a slight leaching of PPy.
Our composite was successful as an active packaging on meat (liver) as bacteria
were killed by contact, thereby preventing the spread of possible diseases. While
it has not been tested on bacteria found in medicine, TOCN/PVA-PPy film may be
able to act as an active sterile packaging for surgical instruments.
PMID- 27612794
TI - Wear studies on ZrO2-filled PEEK as coating bearing materials for artificial
cervical discs of Ti6Al4V.
AB - Polyetheretherketone (PEEK) and its composite coatings are believed to be the
potential candidates' bio-implant materials. However, these coatings have not yet
been used on the surface of titanium-based orthopedics and joint products and
very few investigations on the tribological characteristics could be found in the
published literature till date. In this study, the wettabilities, composition and
micro-hardness were characterized using contact angle measurement, scanning
electron microscopy (SEM) and hardness tester. The tribological tests were
conducted using a ball-on-disc contact pair under 25% newborn calf serum (NCS)
lubricated condition. For comparison, bare Ti6Al4V was studied. The obtained
results revealed that those PEEK/ZrO2 composite coatings could improve the
tribological properties of Ti6Al4V significantly. Adhesive wear and mild abrasive
wear might be the dominant wear and failure mechanisms for PEEK/ZrO2 composite
coatings in NCS lubricated condition. After comprehensive evaluation in the
present study, 5wt.% ZrO2 nanoparticles filled PEEK coating displayed the optimum
tribological characteristics and could be taken as a potential candidate for the
bearing material of artificial cervical disc.
PMID- 27612795
TI - In vitro analysis of different properties of acrylic resins for ocular prosthesis
submitted to accelerated aging with or without photopolymerized glaze.
AB - The effect of a photopolymerized glaze on different properties of acrylic resin
(AR) for ocular prostheses submitted to accelerated aging was investigated. Forty
discs were divided into 4 groups: N1 AR without glaze (G1); colorless AR without
glaze (G2); N1 AR with glaze (G3); and colorless AR with glaze (G4). All samples
were polished with sandpaper (240, 600 and 800-grit). In G1 and G2, a 1200-grit
sandpaper was also used. In G3 and G4, samples were coated with MegaSeal glaze.
Property analysis of color stability, microhardness, roughness, and surface
energy, and assays of atomic force microscopy, scanning electron microscopy, and
energy-dispersive spectroscopy were performed before and after the accelerated
aging (1008h). Data were submitted to the ANOVA and Tukey Test (p<0.05). Groups
with glaze exhibited statistically higher color change and roughness after aging.
The surface microhardness significantly decreased in groups with glaze and
increased in groups without glaze. The surface energy increased after the aging,
independent of the polishing procedure. All groups showed an increase of surface
irregularities. Photopolymerized glaze is an inadequate surface treatment for AR
for ocular prostheses and it affected the color stability, roughness, and
microhardness. The accelerated aging interfered negatively with the properties of
resins.
PMID- 27612796
TI - Preparation, mechanical property and cytocompatibility of freeze-cast porous
calcium phosphate ceramics reinforced by phosphate-based glass.
AB - In this study, phosphate-based glass (PG) was used as a sintering aid for freeze
cast porous biphasic calcium phosphate (BCP) ceramic, which was sintered under a
lower temperature (1000 degrees C). The phase composition, pore structure,
compressive strength, and cytocompatibility of calcium phosphate composite
ceramics (PG-BCP) were evaluated. The results indicated that PG additive reacted
with calcium phosphate during the sintering process, forming beta-Ca2P2O7; the
ions of sodium and magnesium from PG partially substituted the calcium sites of
beta-calcium phosphate in BCP. The PG-BCP showed good cytocompatibility. The pore
width of the porous PG-BCP ceramics was around 50MUm, regardless of the amount of
PG sintering aid. As the content of PG increased from 0wt.% to 15wt.%, the
compressive strength of PG-BCP increased from 0.02 MP to 0.28MPa. When the PG
additive was 17.5wt.%, the compressive strength of PG-BCP dramatically increased
to 5.66MPa. Addition of 15wt.% PG was the critical point for the properties of PG
BCP. PG is considered as an effective sintering aid for freeze-cast porous
bioceramics.
PMID- 27612797
TI - Investigating the passage of tetramethylpyrazine-loaded liposomes across blood
brain barrier models in vitro and ex vivo.
AB - Tetramethylpyrazine (TMP) is a natural product extracted from Rhizoma Chuanxiong.
Liposomes are an excellent delivery method that is suitable for the penetration
of the blood-brain barrier (BBB). TMP-loaded liposomes are suitable for the
treatment of cerebral ischemic diseases. We measured the morphology, particle
size, zeta-potential, entrapment efficiency, and content of TMP-loaded liposome.
The electrochemical method was adopted to determine entrapment efficiency for the
first time. In addition, their diffusion through BBB models, which were built not
only by in vitro cell culture but also by the ex vivo mouse subcutaneous-mucous
membrane (mSMM) method, was explored. The results showed that TMP and TMP-loaded
liposomes could effectively permeate both BBB models. Therefore, the study
indicated that liposomes were a novel carrier that could deliver TMP across the
body barrier models and then release TMP slowly.
PMID- 27612798
TI - Effect of different carboxylic acids in cyclodextrin functionalization of
cellulose nanocrystals for prolonged release of carvacrol.
AB - Current investigations deal with new surface functionalization strategy of
nanocrystalline cellulose-based substrates to impart active molecule release
properties. In this study, cellulose nanocrystals (CNC) were surface
functionalized with beta-cyclodextrin (beta-CD) using succinic acid (SA) and
fumaric acid (FA) as bridging agents. The main objective of this surface
modification performed only in aqueous media was to obtain new active materials
able to release antibacterial molecules over a prolonged period of time. The
reactions were conducted by immersing the CNC film into a solution composed of
beta-CD, SA and FA, leading to CNC grafting. The materials were characterized by
infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D),
AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC
grafting with beta-CD. The results indicated that beta-CD was successfully
attached to the CNC backbone through the formation of ester bonds. Furthermore,
carvacrol was entrapped by the attached beta-CD and a prolonged release was
confirmed. In particular, CNC grafted to beta-CD in the presence of FA was
selected as the best solution. The antibacterial activity and the controlled
release were studied for this sample. Considerably longer bacterial activity
against B. subtilis was observed for CNC grafted to beta-CD compared to CNC and
CNC-FA, confirming the promising impact of the present strategy.
PMID- 27612799
TI - Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles
based on phenylboronic acid and N-vinylcaprolactam for insulin delivery.
AB - Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was
prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid
(AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and
structure of the polymer were examined by Fourier Transform infrared spectroscopy
(FT-IR) and (1)H-NMR. Dynamic light scattering (DLS), lower critical solution
temperature (LCST) and transmission electron microscopy (TEM) were utilized to
characterize the nanoparticles, CD spectroscopy was used to determine if there
were any changes to the conformation of the insulin, and cell and animal toxicity
were also investigated. The prepared nanoparticles were found to be monodisperse
submicron particles and were glucose- and temperature-sensitive. In addition, the
nanoparticles have good insulin-loading characteristics, do not affect the
conformation of the insulin and show low-toxicity to cells and animals. These
p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other
hypoglycemic protein delivery.
PMID- 27612800
TI - Light output from six battery operated dental curing lights.
AB - Light Curing Units (LCUs) are used daily in almost every dental office to
photocure resins, but because the light is so bright, the user is unable to tell
visually if there are any differences between different LCUs. This study
evaluated the light output from six dental LCUs: Elipar Deep Cure-S (3M ESPE),
Bluephase G2 (Ivoclar Vivadent), Translux 2Wave (Heraeus Kulzer), Optilight Prime
(Gnatus), Slim Blast (First Medica) and Led.B (Guilin Woodpecker) with a fully
charged battery, after 50, and again after 100, 20second light exposures. For
each situation, the radiant power was measured 10 times with a laboratory-grade
power meter. Then, the emission spectrum was measured using a fiber-optic
spectrometer followed by an analysis of the light beam profile. It was found
there were significant differences in the LCU power and the irradiance values
between the LCUs (p<0.01). The Optilight Prime and Slim Blast LCUs showed a
significant reduction in light output after a 50 and 100 exposures, while
Bluephase G2 exhibited a significant reduction only after 100 exposures (p<0.01).
The Bluephase G2 and Translux 2Wave delivered an emission spectrum that had two
distinct wavelength emission peaks. Only the Elipar Deep Cure-S and Bluephase G2
LCUs displayed homogeneous light beam profiles, the other LCUs exhibited highly
non-homogeneous light beam profiles. It was concluded that contemporary LCUs
could have very different light output characteristics. Both manufacturers and
researchers should provide more information about the light output from LCUs.
PMID- 27612801
TI - Skin compatibility and antimicrobial studies on biofunctionalized polypropylene
fabric.
AB - The aim of this study was the development of antimicrobial fabric which can be
used as skin contacting material. The nanosilver loaded bioactive nanogels of
polyacrylamide were prepared by gamma irradiation process and the particle size
was observed to be in the range of 10-50nm. In this study, we used polyethylene
glycol as carrier for the combination of functional nanogel and essential oils
together. Plasma functionalized polypropylene fabric was used as the base
material for the bio-immobilization. Bioactive emulsion was coated on the fabric
which exhibited excellent antimicrobial activity against Staphylococcus aureus
and Escherichia coli. Skin irritation studies were carried out over a period of
3d on Swiss albino mice. Histopathology studies of the fabric did not show
adverse inflammatory response in contact with the skin. The biofunctionalized
fabric offers appear to be promising material for skin contacting applications.
PMID- 27612802
TI - The intracellular fate of an amphipathic pH-responsive polymer: Key
characteristics towards drug delivery.
AB - Biopolymers have become important drug delivery systems for therapeutic molecules
by enhancing their accessibility and efficacy intracellularly. However, the
transport of these drugs across the cell membrane and their release into the
cytosol remain a challenge. The trafficking of poly (l-lysine iso-phthalamide)
grafted with phenylalanine (PP-50) was investigated using an osteosarcoma cell
line (SAOS-2). Colocalisation of this amphipathic biopolymer with endocytosis
tracers, such as transferrin and lactosylceramide, suggested that PP-50 is
partially internalised by both clathrin and caveolin-mediated endocytosis.
Macropinocytosis was also investigated, but a smaller correlation was found
between this mechanism and PP-50 transport. A significant decrease in polymer
mediated calcein uptake was found when cells were pre-incubated with endocytosis
inhibitors, suggesting also the use of a combination of mechanisms for cell
internalisation. In addition, PP-50 colocalisation with endosome and lysosome
pathway markers showed that the polymer was able to escape the endolysosomal
compartment before maturation. This is a critical characteristic of a biopolymer
towards use as drug delivery systems and biomedical applications.
PMID- 27612803
TI - Effect of Ti(+4) on in vitro bioactivity and antibacterial activity of silicate
glass-ceramics.
AB - A novel glass-ceramic series in (48-x) SiO2-36 CaO-4 P2O5-12 Na2O-xTiO2 (where
x=0, 3.5, 7, 10.5 and 14mol %) system was synthesized by crystallization of glass
powders, obtained by melt quenching technique. The differential scanning
calorimetric analysis (DSC) was used to study the non-isothermal crystallization
kinetics of the as prepared glasses. The crystallization behaviour of glasses was
analyzed under non-isothermal conditions, and qualitative phase analysis of glass
ceramics was made by X-ray diffraction. The in vitro bioactivity of synthesized
glass-ceramics was studied in stimulated body fluid at 37 degrees C under static
condition for 24days. The formation of hydroxyl-carbonated apatite layer; evident
of bioactivity of the material, was elucidated by XRD, FTIR, AAS, SEM and EDX
analysis. The result showed that partial substitution of TiO2 with SiO2
negatively influenced bioactivity; it decreased with increase in concentration of
TiO2. As Ti(+4) having stronger field strength as compared to Si(+4) so its
replacement became the cause for reduction in degradation that in turn improved
the chemical stability. The compressive strength was also enhanced with progress
addition of TiO2 in the system. The antibacterial properties were examined
against Staphylococcus Epidermidis. Strong antibacterial efficacy was observed
with the addition of TiO2 in the system.
PMID- 27612804
TI - Hollow and porous hydroxyapatite microspheres prepared with an O/W emulsion by
spray freezing method.
AB - Microspheres with hollow and/or porous structures have been widely used in
various applications. A new method of spraying and freezing emulsions was
developed to prepare hollow HA (hydroxyapatite) microspheres with interconnected
pores by using PVA (polyvinyl alcohol) as emulsifiers and binders. The
relationships between viscosity and shear time or rates were tested and the
dispersing stability of oil in water (O/W) emulsions was characterized with
comparison to suspensions without the addition of oil phase. The effects of solid
loadings of HA and the volume ratio between oil and water on the morphologies of
microspheres were investigated. Hollow HA microspheres with particle diameter of
~20MUm and pore size of ~0.6MUm were successfully obtained by spray freezing
method. Besides, drying and sintering processes were crucial to the formation of
hollow and porous structures, respectively. The gentamicin loading and releasing
of HA porous microspheres with different hollow volumes were tested.
PMID- 27612805
TI - Antibacterial mesoporous molecular sieves modified with polymeric N-halamine.
AB - In this research, a new kind of porous N-halamine material with high
antibacterial efficacies was prepared. Poly [5,5-dimethyl-3-(3'
triethoxysilylpropyl)-hydantoin] (PSPH), an N-halamine precursor, was synthesized
and grafted onto the surface of mesoporous molecular sieves (SBA-15). The
mesoporous molecular sieves modified with the N-halamine polymer could be
rendered biocidal upon exposure to dilute household bleach. The modified
mesoporous molecular sieves were characterized by SEM, TEM, FTIR, XPS, TGA, XRD
and BET analysis. It was found that the PSPH has been successfully grafted on the
surface of mesoporous molecular sieves, and the morphology and structure of the
modified mesoporous molecular sieves were slightly affected. The N-halamine
modified mesoporous molecular sieves showed excellent antibacterial property, and
inactivated 100% of S. aureus and E. coli O157:H7 with 8.05 and 7.92 log
reductions within 1min of contact, respectively. The modified SBA-15 with high
antibacterial efficiency has potential application in water treatment and
biomaterials areas.
PMID- 27612806
TI - Cultures and co-cultures of human blood mononuclear cells and endothelial cells
for the biocompatibility assessment of surface modified AISI 316L austenitic
stainless steel.
AB - Samples of AISI 316L austenitic stainless steel were subjected either to grinding
and polishing procedure, or to grinding and then low temperature glow-discharge
nitriding treatment, or to grinding, nitriding and subsequently coating with
collagen-I. Nitrided samples, even if only ground, show a higher corrosion
resistance in PBS solution, in comparison with ground and polished AISI 316L.
Biocompatibility was evaluated in vitro by incubating the samples with either
peripheral blood mononuclear cells (PBMC) or human umbilical vein endothelial
cells (HUVEC), tested separately or in co-culture. HUVEC-PBMC co-culture and co
incubation of HUVEC with PBMC culture medium, after the previous incubation of
PBMC with metallic samples, allowed to determine whether the incubation of PBMC
with the different samples might affect HUVEC behaviour. Many biological
parameters were considered: cell proliferation, release of cytokines, matrix
metalloproteinases (MMPs) and sICAM-1, gelatinolytic activity of MMPs, and ICAM-1
protein expression. Nitriding treatment, with or without collagen coating of the
samples, is able to ameliorate some of the biological parameters taken into
account. The obtained results point out that biocompatibility may be successfully
tested in vitro, using cultures of normal human cells, as blood and endothelial
cells, but more than one cell line should be used, separately or in co-culture,
and different parameters should be determined, in particular those correlated
with inflammatory phenomena.
PMID- 27612807
TI - Nano-structures mediated co-delivery of therapeutic agents for glioblastoma
treatment: A review.
AB - Glioblastoma is a malignant brain tumor and leads to death in most patients.
Chemotherapy is a common method for brain cancer in clinics. However, the recent
advancements in the chemotherapy of brain tumors have not been efficient enough.
With the advancement of nanotechnology, the used drugs can enhance chemotherapy
efficiency and increase the access to brain cancers. Combination of therapeutic
agents has been recently attracted great attention for glioblastoma chemotherapy.
One of the early benefits of combination therapies is the high potential to
provide synergistic effects and decrease adverse side effects associated with
high doses of single anticancer drugs. Therefore, brain tumor treatments with
combination drugs can be considered as a crucial approach for avoiding tumor
growth. This review investigates current progress in nano-mediated co-delivery of
therapeutic agents with focus on glioblastoma chemotherapy prognosis.
PMID- 27612808
TI - Crosslinked pullulan/cellulose acetate fibrous scaffolds for bone tissue
engineering.
AB - Natural polymer based fibrous scaffolds have been explored for bone tissue
engineering applications; however, their inadequate 3-dimensionality and poor
mechanical properties are among the concerns for their use as bone substitutes.
In this study, pullulan (P) and cellulose acetate (CA), two polysaccharides, were
electrospun at various P/CA ratios (P80/CA20, P50/CA50, and P20/CA80%) to develop
3D fibrous network. The scaffolds were then crosslinked with trisodium
trimetaphosphate (STMP) to improve the mechanical properties and to delay fast
weight loss. The lowest weight loss was observed for the groups that were
crosslinked with P/STMP 2/1 for 10min. Fiber morphologies of P50/CA50 were more
uniform without phase separation and this group was crosslinked most efficiently
among groups. It was found that mechanical properties of P20/CA80 and P50/CA50
were higher than that of P80/CA20. After crosslinking strain values of P50/CA50
scaffolds were improved and these scaffolds became more stable. Unlike P80/CA20,
uncrosslinked P50/CA50 and P20/CA80 were not lost in PBS. Among all groups,
crosslinked P50/CA50 scaffolds had more uniform pores; therefore this group was
used for bioactivity and cell culture studies. Apatite-like structures were
observed on fibers after SBF incubation. Human Osteogenic Sarcoma Cell Line (Saos
2) seeded onto crosslinked P50/CA50 scaffolds adhered and proliferated. The
functionality of cells was tested by measuring ALP activity of the cells and the
results indicated their osteoblastic differentiation. In vitro tests showed that
scaffolds were cytocompatible. To sum up, crosslinked P50/CA50 scaffolds were
proposed as candidate cell carriers for bone tissue engineering applications.
PMID- 27612809
TI - Accelerated cell-surface interlocking on plasma polymer-modified porous ceramics.
AB - Excellent osseointegration of permanent implants is crucial for the long lasting
success of the implantation. To improve the osseointegrative potential, bio-inert
titanium alloy surfaces (Ti6Al4V) are modified by plasma chemical oxidation
(PCO(r)) of the titanium-oxide layer to a non-stoichiometric, amorphous calcium
phosphate layer. The native titanium-oxide film measuring only a few nanometers
is converted by PCO(r) to a thick porous calcium phosphate layer of about 10MUm.
In a second step the PCO surface is combined with a cell adhesive plasma
polymerized allylamine (PPAAm) nano film (5 and 50nm). Independent of the PPAAm
coating homogeneity, the human osteoblast-like MG-63 cells show a remarkable
increase in cell size and well-developed filopodia. Analyses of the actin
cytoskeleton reveal that the cells mold to the pore shape of the PPAAm-covered
PCO, thereby establishing a strong attachment to the surface. Interestingly, we
could demonstrate that even though our untreated PCO shows excellent
hydrophilicity, this alone is not sufficient to facilitate fast cell spreading,
but the positive surface charges mediated by PPAAm. This multilayer composite
material guarantees enhanced interlocking of the cells with the porous surface.
PMID- 27612811
TI - Fabrication of hydrogel based nanocomposite scaffold containing bioactive glass
nanoparticles for myocardial tissue engineering.
AB - Selecting suitable cell sources and angiogenesis induction are two important
issues in myocardial tissue engineering. Human endometrial stromal cells (EnSCs)
have been introduced as an abundant and easily available resource in regenerative
medicine. Bioactive glass is an agent that induces angiogenesis and has been
studied in some experiments. The aim of this study was to investigate in vitro
differentiation capacity of endometrial stem cells into cardiomyocyte lineage and
to evaluate capability of bioactive glass nanoparticles toward EnSCs
differentiation into endothelial lineage and angiogenesis on hydrogel scaffold.
Our findings suggests that endometrial stem cells could be programmed into
cardiomyocyte linage and considered a suitable cell source for myocardial
regeneration. This experiment also revealed that inclusion of bioactive glass
nanoparticles in hydrogel scaffold could improve angiogenesis through
differentiating EnSCs toward endothelial lineage and increasing level of vascular
endothelial growth factor secretion.
PMID- 27612810
TI - Injectable calcium phosphate with hydrogel fibers encapsulating induced
pluripotent, dental pulp and bone marrow stem cells for bone repair.
AB - Human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs),
dental pulp stem cells (hDPSCs) and bone marrow MSCs (hBMSCs) are exciting cell
sources in regenerative medicine. However, there has been no report comparing
hDPSCs, hBMSCs and hiPSC-MSCs for bone engineering in an injectable calcium
phosphate cement (CPC) scaffold. The objectives of this study were to: (1)
develop a novel injectable CPC containing hydrogel fibers encapsulating stem
cells for bone engineering, and (2) compare cell viability, proliferation and
osteogenic differentiation of hDPSCs, hiPSC-MSCs from bone marrow (BM-hiPSC-MSCs)
and from foreskin (FS-hiPSC-MSCs), and hBMSCs in CPC for the first time. The
results showed that the injection did not harm cell viability. The porosity of
injectable CPC was 62%. All four types of cells proliferated and differentiated
down the osteogenic lineage inside hydrogel fibers in CPC. hDPSCs, BM-hiPSC-MSCs,
and hBMSCs exhibited high alkaline phosphatase, runt-related transcription
factor, collagen I, and osteocalcin gene expressions. Cell-synthesized minerals
increased with time (p<0.05), with no significant difference among hDPSCs, BM
hiPSC-MSCs and hBMSCs (p>0.1). Mineralization by hDPSCs, BM-hiPSC-MSCs, and
hBMSCs inside CPC at 14d was 14-fold that at 1d. FS-hiPSC-MSCs were inferior in
osteogenic differentiation compared to the other cells. In conclusion, hDPSCs, BM
hiPSC-MSCs and hBMSCs are similarly and highly promising for bone tissue
engineering; however, FS-hiPSC-MSCs were relatively inferior in osteogenesis. The
novel injectable CPC with cell-encapsulating hydrogel fibers may enhance bone
regeneration in dental, craniofacial and orthopedic applications.
PMID- 27612812
TI - In vitro evaluation of actively targetable superparamagnetic nanoparticles to the
folate receptor positive cancer cells.
AB - Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA
formulation was reported. Initially fabricated superparamagnetic iron oxide
nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration
as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent
was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting
the specific receptors expressed on the FAR+ cancer cells. Physiochemical
characterizations were then performed to assure required properties like
stability, size, phase purity, surface morphology, chemical integrity and
magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF
1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of
SPIONs-CA-FA. There were no morphological changes and lysis in contact with
erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA
binding to FAR+ cell lines was assured via qualitative and quantitative in vitro
binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for
biomedical applications like magnetic hyperthermia and drug delivery. The in
vitro findings presented in this study need to be compared with those of in vivo
studies.
PMID- 27612813
TI - Generating nanoparticles containing a new 4-nitrobenzaldehyde thiosemicarbazone
compound with antileishmanial activity.
AB - Thiosemicarbazones are an important class of compounds that have been extensively
studied in recent years, mainly because of their broad profile of pharmacological
activity. A new 4-nitrobenzaldehyde thiosemicarbazone compound (BZTS) that was
derived from S-limonene has been demonstrated to have significant antiprotozoan
activity. However, the hydrophobic characteristic of BZTS limits its
administration and results in low oral bioavailability. In the present study, we
proposed the synthesis of nanoparticle-based block copolymers that can
encapsulate BZTS, with morphological evaluation of the nanoparticle suspensions
being performed by transmission and cryo-transmission electronic microscopy. The
mean particle sizes of the nanoparticle suspensions were determined by static
light and dynamic light scattering (SLS/DLS), and the hydrodynamic radius (Rh)
was determined using the Stokes-Einstein equation. The zeta potential (zeta) and
polydispersity index (PDI) were also determined. The entrapment encapsulation
efficiency of the BZTS nanoparticles was measured by ultraviolet
spectrophotometry. In vitro activity of BZTS nanoparticle suspensions against
intracellular amastigotes of Leishmania amazonensis and cytotoxic activity were
also evaluated. The results showed the production of spherical nanoparticles with
varied sizes depending on the hydrophobic portion of the amphiphilic diblock
copolymers used. Significant concentration-dependent inhibitory activity against
intracellular amastigotes was observed, and low cytotoxic activity was
demonstrated against macrophages.
PMID- 27612814
TI - Novel polyvinyl alcohol-bioglass 45S5 based composite nanofibrous membranes as
bone scaffolds.
AB - Composite nanofibrous membranes based on sol-gel derived 45SiO2 24.5CaO 24.5 Na2O
6 P2O5 (bioglass, BG) and 43SiO2 24.5CaO 24.5 Na2O 6 P2O5 2Fe2O3 (magnetic
bioglass, MBG) blended with polyvinyl alcohol (PVA) have been electrospun. These
low cost membranes were mostly amorphous in structure with minor crystalline
(sodium calcium phosphate) precipitates. All membranes were biodegradable. Among
these, the composites exhibited higher tensile strength, better proliferation of
human osteosarcoma MG63 cells and higher alkaline phosphatase enzyme activity
than the bare PVA membrane, indicating their potential in bone tissue
engineering. The magnetic PVA-MBG scaffold was also found to be a promising
candidate for magnetic hyperthermia application.
PMID- 27612815
TI - Improving hemocompatibility and accelerating endothelialization of vascular
stents by a copper-titanium film.
AB - Bio-inorganic films and drug-eluting coatings are usually used to improve the
hemocompatibility and inhibit restenosis of vascular stent; however, above bio
performances couldn't combine together with single materials. In the present
study, we reported a simple approach to fabricate a metal film with the aim of
imparting the stent with good blood compatibility and accelerating
endothelialization. The films with various ratios of Cu and Ti were prepared
through the physical vapor deposition. Phase structure and element composition
were investigated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy
(XPS), respectively. The releasing volume of copper ion in Cu/Ti film was
determined by immersing test. The hemolysis ratio, platelet adhesion and clotting
time were applied to evaluate the hemocompatibility. The proliferative behaviors
of endothelial cells and smooth muscle cells under certain copper concentration
were investigated in vitro and in vivo. Results indicated that copper-titanium
films exhibited good hemocompatibility in vitro; however, the increase of Cu/Ti
ratio could lead to increasing hemolysis ratio. Endothelial cells displayed more
proliferative than smooth muscle cells when the copper concentration was
<7.5MUg/ml, however both cells tended to apoptosis to some degree when the copper
concentration was increased. The complete endothelialization of the film with low
copper in vivo was observed at the 2nd week, indicating that the copper-titanium
film with the lower copper concentration could promote endothelialization.
Therefore, the inorganic copper-titanium film could be potential biomaterials to
improve blood compatibility and accelerating endothelialization of vascular
stents.
PMID- 27612816
TI - Antibacterial performance and in vivo diabetic wound healing of curcumin loaded
gum tragacanth/poly(epsilon-caprolactone) electrospun nanofibers.
AB - In this study we describe the potential of electrospun curcumin-loaded
poly(epsilon-caprolactone) (PCL)/gum tragacanth (GT) (PCL/GT/Cur) nanofibers for
wound healing in diabetic rats. These scaffolds with antibacterial property
against methicillin resistant Staphylococcus aureus as gram positive bacteria and
extended spectrum beta lactamase as gram negative bacteria were applied in two
forms of acellular and cell-seeded for assessing their capability in healing full
thickness wound on the dorsum of rats. After 15days, pathological study showed
that the application of GT/PCL/Cur nanofibers caused markedly fast wound closure
with well-formed granulation tissue dominated by fibroblast proliferation,
collagen deposition, complete early regenerated epithelial layer and formation of
sweat glands and hair follicles. No such appendage formation was observed in the
untreated controls during this duration. Masson's trichrome staining confirmed
the increased presence of collagen in the dermis of the nanofiber treated wounds
on day 5 and 15, while the control wounds were largely devoid of collagen on day
5 and exhibited less collagen amount on day 15. Quantification analysis of
scaffolds on day 5 confirmed that, tissue engineered scaffolds with increased
amount of angiogenesis number, granulation tissue area (MU(2)), fibroblast
number, and decreased epithelial gap (MU) can be more effective compared to
GT/PCL/Cur nanofibers.
PMID- 27612817
TI - Dynamic contact angle cycling homogenizes heterogeneous surfaces.
AB - In order to reduce restenosis, the necessity to develop the appropriate coating
material of metallic stent is a challenge for biomedicine and scientific research
over the past decade. Therefore, biodegradable copolymers of poly((R,S)-3,3
dimethylmalic acid) (PDMMLA) were prepared in order to develop a new coating
exhibiting different custom groups in its side chain and being able to carry a
drug. This material will be in direct contact with cells and blood. It consists
of carboxylic acid and hexylic groups used for hydrophilic and hydrophobic
character, respectively. The study of this material wettability and dynamic
surface properties is of importance due to the influence of the chemistry and the
potential motility of these chemical groups on cell adhesion and polymer kinetic
hydrolysis. Cassie theory was used for the theoretical correction of contact
angles of these chemical heterogeneous surfaces coatings. Dynamic Surface
Analysis was used as practical homogenizer of chemical heterogeneous surfaces by
cycling during many cycles in water. In this work, we confirmed that, unlike
receding contact angle, advancing contact angle is influenced by the difference
of only 10% of acidic groups (%A) in side-chain of polymers. It linearly
decreases with increasing acidity percentage. Hysteresis (H) is also a sensitive
parameter which is discussed in this paper. Finally, we conclude that cycling
provides real information, thus avoiding theoretical Cassie correction. H(10)is
the most sensible parameter to %A.
PMID- 27612818
TI - In vitro study of a new biodegradable nanocomposite based on poly propylene
fumarate as bone glue.
AB - A novel poly propylene fumarate (PPF)-based glue which is reinforced by
nanobioactive glass (NBG) particles and promoted by hydroxyethyl methacrylate
(HEMA) as crosslinker agent, was developed and investigated for bone-to-bone
bonding applications. In-vitro bioactivity, biodegradability, biocompatibility,
and bone adhesion were tested and the results have verified that it can be used
as bone glue. In an in-vitro condition, the prepared nanocomposite (PPF/HEMA/NBG)
showed improved adhesion to wet bone surfaces. The combined tension and shear
resistance between two wet bone surfaces was measured, and its maximum value was
9+/-59MPa. To investigate the bioactivity and biodegradability of the
nanocomposite, it has been immersed in simulated body fluid (SBF). After 14days
exposure to SBF, a hydroxyapatite (HA) layer formed on the surface of the
composite confirms the bioactivity of this material. In the XRD pattern of the
nanocomposite surface, the HA characteristic diffraction peak at theta=26 and
31.8 were observed. Also, by monitoring the weight change after 8weeks immersion
in SBF, the mass loss was about 16.46wt%. It has been confirmed that this
nanocomposite is a biodegradable material. Also, bioactivity and biodegradability
of nanocomposite have been proved by SEM images. It has been showed that by using
NBG particles and HEMA precursor, mechanical properties increased significantly.
The ultimate tensile strength (UTS) of nanocomposite which contains 20% NBG and
the ratio of 70/30wt% PPF/HEMA (PHB.732) was approximately 62MPa, while the UTS
in the pure PPF/HEMA was about 32MPa. High cell viability in this nanocomposite
(MTT assays, 85-95%) can be attributed to the NBG nature which contains calcium
phosphate and is similar to physiological environment. Furthermore, it possesses
biomineralization and biodegradation which significantly affected by impregnation
of hydrophilic HEMA in the PPF-based polymeric matrix. The results indicated that
the new synthesized biodegradable PPF/HEMA/NBG composite is suitable for
biomedical applications especially as biodegradable bone glue in orthopedic
surgeries.
PMID- 27612819
TI - Effect of the existing form of Cu element on the mechanical properties, bio
corrosion and antibacterial properties of Ti-Cu alloys for biomedical
application.
AB - Ti-Cu alloys have exhibited strong antibacterial ability, but Ti-Cu alloys
prepared by different processes showed different antibacterial ability. In order
to reveal the controlling mechanism, Ti-Cu alloys with different existing forms
of Cu element were prepared in this paper. The effects of the Cu existing form on
the microstructure, mechanical, corrosion and antibacterial properties of Ti-Cu
alloys have been systematically investigated. Results have shown that the as-cast
Ti-Cu alloys showed a higher hardness and mechanical strength as well as a higher
antibacterial rate (51-64%) but a relatively lower corrosion resistance than pure
titanium. Treatment at 900 degrees C/2h (T4) significantly increased the hardness
and the strength, improved the corrosion resistance but had little effect on the
antibacterial property. Treatment at 900 degrees C/2h+400 degrees C/12h (T6)
increased further the hardness and the mechanical strength, improved the
corrosion resistance and but also enhanced the antibacterial rate (>90%)
significantly. It was demonstrated that the Cu element in solid solution state
showed high strengthening ability but low antibacterial property while Cu element
in Ti2Cu phase exhibited strong strengthening ability and strong antibacterial
property. Ti2Cu phase played a key role in the antibacterial mechanism. The
antibacterial ability of Ti-Cu alloy was strongly proportional to the Cu content
and the surface area of Ti2Cu phase. High Cu content and fine Ti2Cu phase would
contribute to a high strength and a strong antibacterial ability.
PMID- 27612820
TI - Chitosan derivatives/reduced graphene oxide/alginate beads for small-molecule
drug delivery.
AB - This work reported chitosan derivatives (CSD)/reduced graphene oxide (rGO)
blending with alginate to prepare hydrogel beads for small-molecule drug delivery
for the first time. At the beginning, graphene oxide (GO) was successfully
reduced using diverse CSD as reducing and stabilizing agents via facile heating.
Then the obtained CSD/rGO was blended with alginate and crosslinked into hydrogel
beads in CaCl2 solution. Finally, the beads were systematically evaluated as
novel vehicles for pH-responsive small-molecule drug delivery. The optimal
CSD/rGO/alginate beads showed a high drug-loading efficiency of 82.8% on small
molecule fluorescein sodium (FL), outstanding sustainable release of 71.6% upon
150h at a physiological pH and quick-release of 82.4% drug content at 20h in an
acidic medium. Additionally, the cytotoxicity assay result suggested that the
CSD/rGO/alginate beads showed negligible cytotoxicity to hepatic stellate cell
lines, opening up possibilities for safe and efficient drug delivery.
PMID- 27612821
TI - Fabrication of dense alpha-alumina layer on Ti-6Al-4V alloy hybrid for bearing
surfaces of artificial hip joint.
AB - Recent advances in hip replacements are focused towards producing reliable
bearing surfaces to enhance their longevity. In this perspective, progressive
attempts have been made to improve the wear resistance of polyethylene to
eliminate osteolysis and mechanical reliability of brittle alumina ceramics, but
in vain. It is proposed that both high wear resistance and mechanical reliability
can be retained if a thin layer of dense alumina is formed onto high toughness Ti
6Al-4V alloy. For this purpose, we devised a unique methodology in which a layer
of Al metal was deposited onto the Ti alloy substrate by cold spraying (CS),
followed by a heat treatment to form Al3Ti reaction layer at their interface to
improve adhesion and subsequent micro-arc oxidation (MAO) treatment to transform
Al to alumina layer. An optimal MAO treatment of cold sprayed Al formed an
adherent and dense alpha-alumina layer with high Vickers hardness matching with
that of sintered alumina used as a femoral head. Structure-phase-property
relationships in dense alpha-alumina layer have been revealed and discussed in
the light of our research findings. The designed alumina/Ti alloy hybrid might be
a potential candidate for reliable bearing surfaces of artificial hip joint.
PMID- 27612822
TI - In vitro biocompatibility of titanium after plasma surface alloying with boron.
AB - Recently, the effect of different sizes of precursor powders during surface
plasma alloying modification on the properties of titanium surface was studied.
In this work we show in vitro test results of the titanium (alpha-Ti) after
plasma surface alloying with boron (B). Ti-B nanopowders with 2 and 10wt% B were
deposited onto microcrystalline Ti substrate. The in vitro cytocompatibility of
these biomaterials was evaluated and compared with a conventional
microcrystalline Ti. During the studies, established cell line of human gingival
fibroblasts and osteoblasts were cultured in the presence of tested materials,
and its survival rate and proliferation activity were examined. For this purpose,
MTT assay, flow cytometric and fluorescent microscopic evaluation were made.
Biocompatibility tests carried out indicate that the Ti after plasma surface
alloying with B could be a possible candidate for dental implants and other
medicinal applications. Plasma alloying is a promising method for improving the
properties of titanium, thus increasing the field of its applications.
PMID- 27612823
TI - Development of novel biocompatible hybrid nanocomposites based on polyurethane
silica prepared by sol gel process.
AB - Due to high biocompatibility, polyurethane has found many applications,
particularly in development of biomedical devices. A new nanocomposite based on
thermoset polyurethane and silica nanoparticles was synthesized using sol-gel
method. Sol-gel process was fulfilled in two acidic and basic conditions by using
tetraethylorthosilicate (TEOS) and trimethoxyisocyanatesilane as precursors. The
hybrid films characterized for mechanical and surface properties using tensile
strength, contact angle, ATR-FTIR and scanning electron microscopy.
Biocompatibility and cytotoxicity of the hybrids were assessed using standard
MTT, LDH and TUNEL assays. The results revealed that incorporation of silica
nanoparticles was significantly improved tensile strength and mechanical
properties of the hybrids. Based on the contact angle results, silica
nanoparticles increased hydrophilicity of the hybrids. Biocompatibility by using
human lung epithelial cell line (MRC-5) demonstrated that the hybrids were
significantly less cytotoxic compared to pristine polymer as tested by MTT and
LDH assays. TUNEL assay revealed no signs of apoptosis in all tested samples. The
results of this study demonstrated that incorporation of silica nanoparticles
into polyurethane lead to the enhancement of biocompatibility, indicating that
these hybrids could potentially be used in biomedical field in particular as a
new coating for medical implants.
PMID- 27612824
TI - The effects of acoustic vibration on fibroblast cell migration.
AB - Cells are known to interact and respond to external mechanical cues and recent
work has shown that application of mechanical stimulation, delivered via acoustic
vibration, can be used to control complex cell behaviours. Fibroblast cells are
known to respond to physical cues generated in the extracellular matrix and it is
thought that such cues are important regulators of the wound healing process.
Many conditions are associated with poor wound healing, so there is need for
treatments/interventions, which can help accelerate the wound healing process.
The primary aim of this research was to investigate the effects of mechanical
stimulation upon the migratory and morphological properties of two different
fibroblast cells namely; human lung fibroblast cells (LL24) and subcutaneous
areolar/adipose mouse fibroblast cells (L929). Using a speaker-based system, the
effects of mechanical stimulation (0-1600Hz for 5min) on the mean cell migration
distance (MUm) and actin organisation was investigated. The results show that
100Hz acoustic vibration enhanced cell migration for both cell lines whereas
acoustic vibration above 100Hz was found to decrease cell migration in a
frequency dependent manner. Mechanical stimulation was also found to promote
changes to the morphology of both cell lines, particularly the formation of
lamellipodia and filopodia. Overall lamellipodia was the most prominent actin
structure displayed by the lung cell (LL24), whereas filopodia was the most
prominent actin feature displayed by the fibroblast derived from subcutaneous
areolar/adipose tissue. Mechanical stimulation at all the frequencies used here
was found not to affect cell viability. These results suggest that low-frequency
acoustic vibration may be used as a tool to manipulate the mechanosensitivity of
cells to promote cell migration.
PMID- 27612825
TI - Effect of hydroxyapatite surface morphology on cell adhesion.
AB - We obtained hydroxyapatite (HAp) materials as a block by mixing HAp nanoparticles
and polymer, and then calcining the mixtures. The surface morphology of the HAp
materials was tuned by varying heat treatment conditions. After calcining the
mixtures at 1200 or 800 degrees C for 4h, the surface morphology of the HAp
materials was flat or convexo-concave, respectively. The flat surface morphology,
which showed micrometer-ordered grain boundaries, was formed by the aggregation
of HAp nanoparticles. On the other hand, the convexo-concave surface morphology
resulted from the agglomeration of HAp nanoparticles after heat treatment at 800
degrees C for 4h with nanometer-ordered particle size. We tested cell adhesion to
HAp materials with flat or convexo-concave surface morphology and found that
cells adhered well to the flat HAp materials but not to the convexo-concave HAp
materials. This technique for selectively preparing HAp materials with flat or
convexo-concave surface morphology was very easy because we merely mixed
commercial HAp nanoparticles with polymer and then calcined the mixtures. As a
result, the heat treatment temperature affected the surface morphology of our HAp
materials, and their surface morphologies contributed to cell adhesion
independently of other material properties.
PMID- 27612826
TI - Effect of fibronectin adsorption on osteoblastic cellular responses to
hydroxyapatite and alumina.
AB - Initial cellular responses following implantation are important for inducing
osteoconduction. We investigated cell adhesion, spreading, proliferation and
differentiation of mouse MC3T3-E1 osteoblastic cells on untreated or fibronectin
(Fn)-coated discs of hydroxyapatite (HAp) or alpha-type alumina (alpha-Al2O3). Fn
coating significantly enhanced adhesion and spreading of MC3T3-E1 cells on HAp,
but did not affect MC3T3-E1 cell proliferation and differentiation on HAp or
alpha-Al2O3. Fn-coated HAp likely does not stimulate pre-osteoblast cells to
initiate the process of osteoconduction; however, Fn adsorption might affect the
response of inflammatory cells to the implanted material or, in conjunction with
other serum proteins, stimulate pre-osteoblast cell proliferation and
differentiation. Further studies on the effect of serum proteins in cell culture
and the efficacy of Fn-coated HAp and alpha-Al2O3in vivo are warranted.
PMID- 27612827
TI - Thixotropic injectable hydrogel using a polyampholyte and nanosilicate prepared
directly after cryopreservation.
AB - Success of tissue engineering applications in regenerative medicine requires the
preservation of tissue-engineered products at a low temperature. This can be
successfully achieved by the use of cryoprotective agent (CPA). In this study, we
formulated a unique injectable hydrogel for the purpose of cell delivery after
cryopreservation by using polyampholyte CPA. The polyampholyte showed excellent
post-thaw cell survival, and after thawing, the polymeric CPA did not have to be
removed because of its low cytotoxicity. The polyampholyte could be transformed
into a hydrogel by mixing with nanosilicates. Previously, nanosilicates were used
to improve mechanical properties, but this is the first report of the use of a
nanosilicate together with CPA to formulate hydrogels. Inclusion of the
nanosilicate led to the formation of thixotropic hydrogels, which can be injected
using fine needles. These gels with tunable mechanical properties can be injected
into defect sites to form scaffolds for cell growth and tissue repair, and they
do not require any separate seeding of cells before injection, thus eliminating
the need for cell harvesting and cell maintenance. This is a distinct system in
which cells can be cryopreserved until before usage; when required, the cells in
the polyampholyte can be revived to their original state and the thixotropic
hydrogel can be formed. The combination of thixotropy and cytocompatibility of
the gels could enable a wide range of biomedical applications such as cell
delivery and orthopedic repair.
PMID- 27612828
TI - Polyethylene/silver-nanofiber composites: A material for antibacterial films.
AB - Silver nanofibers (Ag-Nfbs)~80nm in diameter were synthesized by hydrothermal
treatment. The nanofibers (3 and 5wt%) were added in the initial feed together
with the catalytic system. Polymerizations in an ethylene atmosphere were
performed, yielding PE nanocomposites in situ with 3 and 5wt% content of Ag-Nfbs.
The antibacterial effect of the silver-nanofiber composites was evaluated after
incubation of Escherichia coli ATCC 25923 for 8h on their surface. Bacterial
viability tests showed that the silver-nanofiber composites inhibited the growth
of Escherichia coli ATCC 25923 by 88 and 56%. This behavior is attributed to
increased silver ions release from the nanocomposite. TEM analysis showed that
the antibacterial effect is associated with membrane disruption but not with
changes in shape.
PMID- 27612829
TI - Durable grafting of silkworm pupa protein onto the surface of polyethylene
terephthalate fibers.
AB - In this paper, reactive -NH2 groups (8.36*10(-6)mol/g fabric) were introduced to
the surface of polyethylene terephthalate (PET) fabrics by a nitration and
reduction method, and epoxy groups were introduced to silkworm pupa protein (SPP)
by reaction with epoxy chloropropane. PET-SPP composite fabrics were then
prepared by reaction of these two precursors. The results showed that the SPP was
firmly grafted onto the PET fabric surface and that the hydrophilicity of the
fabric was markedly improved by the grafting of SPP. SEM images revealed a layer
of substance covering the surface of the PET fibers, and XPS investigation showed
that the nitrogen content of the PET-SPP fabric was higher than that of the
original PET fabric (2.32% vs 0%). ATR-FTIR adsorption bands at 1653 and 1543cm(
1) suggested the successful grafting of SPP onto the PET fabric surface. The DSC
and TG of the PET fibers demonstrated that the thermal stability of the original
PET fibers was maintained well by the SPP-grafted PET fibers. The breaking
strength, bending rigidity, air permeability, and crease recovery angle of the
original PET fabric were also retained by the SPP-grafted PET fabric.
PMID- 27612830
TI - Evaluation of DNA binding, DNA cleavage, protein binding, radical scavenging and
in vitro cytotoxic activities of ruthenium(II) complexes containing 2,4-dihydroxy
benzylidene ligands.
AB - The new ruthenium(II) complexes with hydrazone ligands, 4-Methyl-benzoic acid
(2,4-dihydroxy-benzylidene)-hydrazide (HL(1)), 4-Methoxy-benzoic acid (2,4
dihydroxy-benzylidene)-hydrazide (HL(2)), 4-Bromo-benzoic acid (2,4-dihydroxy
benzylidene)-hydrazide (HL(3)), were synthesized and characterized by various
spectro analytical techniques. The molecular structures of the ligands were
confirmed by single crystal X-ray diffraction technique. The DNA binding studies
of the ligands and complexes were examined by absorption, fluorescence, viscosity
and cyclic voltammetry methods. The results indicated that the ligands and
complexes could interact with calf thymus DNA (CT-DNA) through intercalation. The
DNA cleavage activity of the complexes was evaluated by gel electrophoresis
assay, which revealed that the complexes are good DNA cleaving agents. The
binding interaction of the ligands and complexes with bovine serum albumin (BSA)
was investigated using fluorescence spectroscopic method. Antioxidant studies
showed that the complexes have a strong radical scavenging properties. Further,
the cytotoxic effect of the complexes examined on cancerous cell lines showed
that the complexes exhibit significant anticancer activity.
PMID- 27612831
TI - Mechanical properties of additively manufactured octagonal honeycombs.
AB - Honeycomb structures have found numerous applications as structural and
biomedical materials due to their favourable properties such as low weight, high
stiffness, and porosity. Application of additive manufacturing and 3D printing
techniques allows for manufacturing of honeycombs with arbitrary shape and wall
thickness, opening the way for optimizing the mechanical and physical properties
for specific applications. In this study, the mechanical properties of honeycomb
structures with a new geometry, called octagonal honeycomb, were investigated
using analytical, numerical, and experimental approaches. An additive
manufacturing technique, namely fused deposition modelling, was used to fabricate
the honeycomb from polylactic acid (PLA). The honeycombs structures were then
mechanically tested under compression and the mechanical properties of the
structures were determined. In addition, the Euler-Bernoulli and Timoshenko beam
theories were used for deriving analytical relationships for elastic modulus,
yield stress, Poisson's ratio, and buckling stress of this new design of
honeycomb structures. Finite element models were also created to analyse the
mechanical behaviour of the honeycombs computationally. The analytical solutions
obtained using Timoshenko beam theory were close to computational results in
terms of elastic modulus, Poisson's ratio and yield stress, especially for
relative densities smaller than 25%. The analytical solutions based on the
Timoshenko analytical solution and the computational results were in good
agreement with experimental observations. Finally, the elastic properties of the
proposed honeycomb structure were compared to those of other honeycomb structures
such as square, triangular, hexagonal, mixed, diamond, and Kagome. The octagonal
honeycomb showed yield stress and elastic modulus values very close to those of
regular hexagonal honeycombs and lower than the other considered honeycombs.
PMID- 27612832
TI - Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and
bioavailability in mice.
AB - Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were
prepared (henceforth referred as lutein nanocapsules) and studied for acute,
subacute oral toxicity and bioavailability of lutein in mice. Prior to examining
the safety of lutein nanocapsules, particle size, zeta potential, surface
morphology and interaction between lutein, PLGA and PL were studied. In acute
study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10
and 100mg/kg body weight (BW) and examined for 2weeks, while in subacute study,
daily mice were gavaged with a dose of 1 and 10mg/kg BW for 4weeks. Results
revealed that mean size and zeta value of lutein nanocapsules were 140nm and
44mV, respectively. Acute and subacute toxicity studies did not show any
mortality or treatment related adverse effect in clinical observations,
ophthalmic examinations, body and organ weights. No toxicity related findings
were observed in hematology, histopathology and other blood and tissue clinical
chemistry parameters. In subacute study, no observed adverse effect level (NOAEL)
of lutein nanocapsules was found to be at a dose of 10mg/kg BW. Feeding lutein
nanocapsules resulted in a significant (p<0.01) increase in lutein level in
plasma and tissue compared to the control group. Lutein nanocapsules did not
cause toxicity in mice. However, human trials are warranted.
PMID- 27612833
TI - Acrylic bone cement and starch: Botanical variety impact on curing parameters and
degradability.
AB - Acrylic bone cements are a conventional solution to heal bone defects. Starch is
often added to the cement to improve its degradability and resorbability. The
most used botanical variety is corn starch; few studies or applications deal with
other varieties. This study focuses on classical formulations based on 2
hydroxyethylmethacrylate but incorporating different starches: waxy maize, corn,
amylo maize, wheat, pea or potato, with or without enzyme (alpha-amylase). A
thermocouple is used to determine the curing parameters: setting time and maximal
temperature. The water uptake depends on the cement immersion time in a
biological fluid and it is studied through sample mass variation analysis. The
weight loss is determined after immersion (function of the time) and drying.
Starch botanical variety and enzyme presence do not impact curing parameters and
water uptake but strongly influence degradability. Water uptake involves
advantageous swelling in situ filling the defect. This study shows that starch
accessibility by the enzyme explains this impact. Grain spatial configuration,
specific surface area and starch distribution in cement give a complementary
explanation of the well-known influence of the ratio amylopectin/amylose. Acrylic
cements incorporating starch can be classified according to their degradability.
PMID- 27612834
TI - Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal
anti-inflammatory drugs.
AB - The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used
pharmaceuticals worldwide. Interestingly, many of them have significant
anticancer properties too. However, the poor water solubility of certain NSAIDs
limits their application for cancer treatment. Nanosizing of such drugs can help
to improve the solubility and this may result in enhanced anticancer activities
too. Moreover, over dosages and the accompanying side effects of NSAIDs can be
minimized by improving their solubility and bioavailability. Successful
nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen
(NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI)
method is reported here. Three water soluble and biocompatible polymers:
polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl
methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles
having spherical morphology with average size below 30nm were thoroughly
characterized using dynamic light scattering and field emission scanning electron
microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold
improvements in the solubility and significant enhancement in the in-vitro drug
release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs
against five different cancer cell lines such as MCF-7 (Human breast cancer cell
line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell
line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell
line) A2780 was performed. All the nanoformulated samples showed improved
anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP
showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP
was more than twice that of doxorubicin which is a standard anticancer drug.
PMID- 27612835
TI - Electrochemical and DFT study of an anticancer and active anthelmintic drug at
carbon nanostructured modified electrode.
AB - The electrochemical response of mebendazole (Meb), an anticancer and effective
anthelmintic drug, was investigated using two different carbon nanostructured
modified glassy carbon electrodes (GCE). Although, compared to unmodified GCE,
both prepared modified electrodes improved the voltammetric response of Meb, the
carbon nanotubes (CNTs) modified GCE showed higher sensitivity and stability.
Therefore, the CNTs-GCE was chosen as a promising candidate for the further
studies. At first, the electrochemical behavior of Meb was studied by cyclic
voltammetry and differential pulse and square wave voltammetry. A one step
reversible, pH-dependent and adsorption-controlled process was revealed for
electro-oxidation of Meb. A possible mechanism for the electrochemical oxidation
of Meb was proposed. In addition, electronic structure, adsorption energy, band
gap, type of interaction and stable configuration of Meb on the surface of
functionalized carbon nanotubes were studied by using density functional theory
(DFT). Obtained results revealed that Meb is weakly physisorbed on the CNTs and
that the electronic properties of the CNTs are not significantly changed.
Notably, CNTs could be considered as a suitable modifier for preparation of the
modified electrode for Meb analysis. Then, the experimental parameters affecting
the electrochemical response of Meb were optimized. Under optimal conditions,
high sensitivity (b(Meb)=dIp,a(Meb)/d[Meb]=19.65MUAMUM(-1)), a low detection
limit (LOD (Meb)=19nM) and a wide linear dynamic range (0.06-3MUM) was resulted
for the voltammetric quantification of Meb.
PMID- 27612836
TI - CdTe amplification nanoplatforms capped with thioglycolic acid for
electrochemical aptasensing of ultra-traces of ATP.
AB - A "signal off" voltammetric aptasensor was developed for the sensitive and
selective detection of ultra-low levels of adenosine triphosphate (ATP). For this
purpose, a new strategy based on the principle of recognition-induced switching
of aptamers from DNA/DNA duplex to DNA/target complex was designed using
thioglycolic acid (TGA)-capped CdTe quantum dots (QDs) as the signal amplifying
nano-platforms. Owing to the small size, high surface-to-volume ratio and good
conductivity, quantum dots were immobilized on the electrode surface for signal
amplification. In this work, methylene blue (MB) adsorbed to DNA was used as a
sensitive redox reporter. The intensity of voltammetric signal of MB was found to
decrease linearly upon ATP addition over a concentration range of 0.1nM to 1.6MUM
with a correlation coefficient of 0.9924. Under optimized conditions, the
aptasensor was able to selectively detect ATP with a limit of detection of 45pM
at 3sigma. The results also demonstrated that the QDs-based amplification
strategy could be feasible for ATP assay and presented a potential universal
method for other small biomolecular aptasensors.
PMID- 27612837
TI - Role of physical and chemical interactions in the antibacterial behavior of ZnO
nanoparticles against E. coli.
AB - Zinc oxide (ZnO) nanoparticles (NPs) exhibit antibacterial activity against both
Gram-positive and Gram-negative bacteria. However, the antimicrobial mechanism of
ZnO NPs remains unclear. In this study, we investigated the interactions among
ZnO NPs, released chemicals (Zn(2+) and Reactive Oxygen Species, ROS) and
Escherichia coli (E. coli) cells. ZnO NPs without contacting with bacterial cells
showed strong antibacterial effect. The results of the leakage of intracellular
K(+) and integrity of carboxyfluoresce in-filled liposomes showed that ZnO NPs
have antimicrobial activity against E. coli by non-specifically disrupting E.
coli membranes. Traces of zinc ions (1.25mg/L) and hydrogen peroxide (from 1.25
to 4.5MUM/L) were detected in ZnO NPs suspensions, but was insufficient to cause
the antibacterial effect. However, the addition of radical scavengers suppressed
the bactericidal effect of ZnO coated films against E. coli, potentially
implicating ROS generation, especially hydroxyl radicals, in the antibacterial
ability of ZnO NPs.
PMID- 27612838
TI - Enhanced gene delivery of low molecular weight PEI by flower-like ZnO
microparticles.
AB - Low molecular weight (1.8 kDa) branched polyethylenimine (PEI) has been used as
non-viral vector for gene delivery because of its low toxicity, however, its
further application in biomedical field has been restricted due to its low gene
transfection efficiency. Herein, ZnO microflowers were prepared to increase the
gene expression level mediated by PEI. Four methods have been applied to tune the
shape of ZnO microstructures. Scanning electron microscopy (SEM) demonstrated the
successful preparation of four kinds of flower like ZnO microparticles. By
loading PEI/pDNA into ZnO microparticles, the formed new complexes showed
enhanced gene transfection compared to PEI/pDNA alone. Cell uptaking experiments
explained a possible mechanism that the tips of ZnO microflowers penetrated into
the surface of cells, thus facilitating the entry of gene cargo into cells. These
findings highlight the potential of needle like microstructure as adjuvant for
efficient biomacromolecular delivery.
PMID- 27612839
TI - Beads, beaded-fibres and fibres: Tailoring the morphology of poly(caprolactone)
using pressurised gyration.
AB - This work focuses on forming bead on string poly(caprolactone) (PCL) by using
gyration under pressure. The fibre morphology of bead on string is an interesting
feature that falls between bead-free fibres and droplets, and it could be
effectively controlled by the rheological properties of spinning dopes and the
major processing parameters of the pressurised gyration system which are working
pressure and rotating speed. Bead products were not always spherical in shape and
tended to be more elliptical, therefore both their width and length were
measured. The average bead width and length produced spanned a range 145-660MUm
and 140-1060MUm, respectively. The average distance between two adjacent beads
(i.e. inter-bead distance) and the bead size (width and length) are shown to be a
function of processing parameters and polymer concentration. An interesting
morphology i.e. beads with short fibre was observed when using a high polymer
concentration. Bead on string structure agglomeration was promoted by a low
polymer concentration. Formation of droplets or agglomerated bead on string is
promoted below 5wt% polymer concentration, and beads with short fibre were
present in the microstructure beyond a polymer concentration of 20wt%.
PMID- 27612840
TI - Recent advancements in regenerative dentistry: A review.
AB - Although human mouth benefits from remarkable mechanical properties, it is very
susceptible to traumatic damages, exposure to microbial attacks, and congenital
maladies. Since the human dentition plays a crucial role in mastication,
phonation and esthetics, finding promising and more efficient strategies to
reestablish its functionality in the event of disruption has been important.
Dating back to antiquity, conventional dentistry has been offering evacuation,
restoration, and replacement of the diseased dental tissue. However, due to the
limited ability and short lifespan of traditional restorative solutions,
scientists have taken advantage of current advancements in medicine to create
better solutions for the oral health field and have coined it "regenerative
dentistry." This new field takes advantage of the recent innovations in stem cell
research, cellular and molecular biology, tissue engineering, and materials
science etc. In this review, the recently known resources and approaches used for
regeneration of dental and oral tissues were evaluated using the databases of
Scopus and Web of Science. Scientists have used a wide range of biomaterials and
scaffolds (artificial and natural), genes (with viral and non-viral vectors),
stem cells (isolated from deciduous teeth, dental pulp, periodontal ligament,
adipose tissue, salivary glands, and dental follicle) and growth factors (used
for stimulating cell differentiation) in order to apply tissue engineering
approaches to dentistry. Although they have been successful in preclinical and
clinical partial regeneration of dental tissues, whole-tooth engineering still
seems to be far-fetched, unless certain shortcomings are addressed.
PMID- 27612841
TI - Copper-polymer nanocomposites: An excellent and cost-effective biocide for use on
antibacterial surfaces.
AB - The development of polymer nanocomposites with antimicrobial properties has been
a key factor for controlling or inhibiting the growth of microorganisms and
preventing foodborne diseases and nosocomial infections. Commercially available
antibacterial products based on silver-polymer are the most widely used despite
the fact that copper is considerably less expensive. The incorporation of copper
nanoparticles as antibacterial agents in polymeric matrices to generate copper
polymer nanocomposites have presented excellent results in inhibiting the growth
of a broad spectrum of microorganisms. The potential applications in food
packaging, medical devices, textiles and pharmaceuticals and water treatment have
generated an increasing number of investigations on preparing copper based
nanocomposites and alternative polymeric matrices, as potential hosts of nano
modifiers. This review presents a comprehensive compilation of previous published
work on the subject, mainly related to the antimicrobial activity of copper
polymer nanocomposites. Within all the phenomenology associated to antibacterial
effects we highlight the possible mechanisms of action. We discuss the
differences in the susceptibility of Gram negative and positive bacteria to the
antibacterial activity of nanocomposites, and influencing factors. As well, the
main applications of copper polymer-metal nanocomposites are described,
considering their physical and chemical characteristics. Finally, some
commercially available copper-polymer nanocomposites are described.
PMID- 27612842
TI - Orbital implants: State-of-the-art review with emphasis on biomaterials and
recent advances.
AB - In the treatment of severe oculo-orbital traumas, intraocular malignancies or
other life-threatening conditions it is sometimes necessary to surgically remove
the patient's diseased eye. Following the removal of the eye, an orbital implant
is inserted into the anophthalmic socket in order to provide satisfactory volume
replacement and restore the aesthetic appearance of a normal eye. Over the last
decades, the implant design and the criteria of materials selection evolved from
simple non-porous polymeric sphere to devices with more complex shape and
functionalities for ensuring better clinical outcomes in the long-term. Polymeric
and ceramic porous implants have gained prominence since their highly
interconnected porous architecture allows them to act as a passive framework for
fibrovascular in-growth offering reduced complication rates and the possibility
of pegging to enhance the motility of the artificial eye. However, there are
still drawbacks to these materials. Some critical aspects of today's orbital
implants include the risk of migration and extrusion, postoperative infections
and low motility transmitted to the aesthetic ocular prosthesis. Hence, the
development of novel biomaterials with enhanced functionalities (e.g.
angiogenesis, antibacterial effect, in situ mouldability) which enable an
improved outcome of eye replacement is more than ever desirable and represents
one of the most challenging topics of research in the field of ocular implants.
This review summarizes the evolution of orbital implants and provides an overview
of the most recent advances in the field as well as some critical remarks for
materials design, selection, characterization and translation to clinical
applications.
PMID- 27612843
TI - Titanium dental implant surfaces obtained by anodic spark deposition - From the
past to the future.
AB - Commercial titanium-based dental implants are obtained applying various methods
such as machining, acid etching, anodization, plasma spraying, grit blasting or
combination techniques yielding materials with smooth or micro-roughened
surfaces. Those techniques are used to optimize the surface properties and to
maximize biocompatibility and bioactivity with bone tissue. Present review is
focused on the material surfaces obtained by anodic spark deposition (ASD). From
the early 1980s till present, the results of numerous studies have shown that
anodically oxidized surfaces with different dopants express a positive effect on
osteoblasts behavior in vitro and osseointegration in vivo. Those surfaces
demonstrated a high biocompatibility and rapid osseointegration in clinical
application. This paper provides an overview of the preparation of implant
surfaces by employing ASD process. Moreover, reviewed are clinically used ASD
implant surfaces (Ticer, TiUnite, Osstem, etc.). The electrolyte variations in
ASD process and their influence on surface properties are given herein. Using
different electrolytes, anode voltages and temperatures, the above fabrication
process can yield various surface morphologies from smooth to rough, porous
surfaces. Furthermore, ASD enables thickening of oxide layers and enrichment with
different dopands from used electrolyte, which hinder release of potentially
toxic titanium ions in surrounding tissue. Particularly exciting results were
achieved by calcium and phosphorus doping of the oxide layer (Ticer, ZL
Microdent; TiUnite, Nobel Biocare Holding AB) which significantly increased the
osteocompatibility. Ticer, a dental implant with anodically oxidized surface and
the first among similar materials employed in clinical practice, was found to
promote fast osteoblast cell differentiation and mineralization processes.
Moreover, Ticer accelerate the integration with the bone, increase the
bone/implant contact and improve primary and secondary stability of the implants.
Additionally, potential innovations in this field such as fabrication of
nanotubes on the implant surfaces as well as novel approaches (e.g. coating with
proteins, nanostructured topography; combining implant body and surface derived
from titanium and zirconia) are elaborated in this review. Besides, biochemical
aspects on implant surface cell/tissue interaction are summarized. From the
clinical point of view implant surfaces fabricated by ASD technology possess fast
and improved osseointegration, high healing rates and long term prognosis.
PMID- 27612845
TI - 16th ISoP Annual Meeting ''Pharmacovigilance for Safer Tomorrow'' Agra, India 16
19 October, 2016 : ABSTRACTS.
PMID- 27612844
TI - Evidence-based arguments in direct democracy: The case of smoking bans in
Switzerland.
AB - This article analyses the use of evidence, such as policy evaluation studies, in
arguments in direct-democratic campaigns. Set in the context of 16 Swiss direct
democratic campaigns on smoking bans, the article compares evidence-based
arguments with arguments that do not refer to evidence. The study adds to the
argumentative direction in evaluation and program planning by showing that in
direct-democratic campaigns, the political use of evaluation results to
substantiate policy preferences is rare. The study shows that around 6% of the
arguments refer to evidence and that evaluation results are mostly cited in
support of causal arguments referring to the effects of policy interventions.
Above all, the results show that policy information is available, at least for
causal arguments, and apparently known in the public discourse but only cited
explicitly when the speaker wants to raise credibility. This applies especially
to researchers, such as evaluators. The results further indicate that the
political use of evaluation results fosters an informed discourse and the
evidence may eventually become common public knowledge. The credentials of
evaluators make them suitable not only for bringing more evaluation results into
the direct-democratic discourse but also for acting as teachers in this
discourse.
PMID- 27612846
TI - Surgery for Diabetic Eye Complications.
AB - New modalities for the treatment of diabetic eye complications have emerged in
the past decade. Nevertheless, many severe diabetic retinopathy complications can
only be treated with vitreoretinal surgery. Technological advances in pars plana
vitrectomy have expanded the gamut of pathologies that can be successfully
treated with surgery. The most common pathologies managed surgically include
vitreous opacities and traction retinal detachment. The indications, surgical
objectives, adjunctive pharmacotherapy, microincisional surgical techniques, and
outcomes of diabetic vitrectomy for proliferative diabetic retinopathy and
diabetic tractional retinal detachment will be discussed. With the availability
of new microincisional vitrectomy technology, wide angle microscope viewing
systems, and pharmacologic agents, vitrectomy can improve visual acuity and
achieve long-term anatomic stability in eyes with severe complications from
proliferative diabetic retinopathy.
PMID- 27612848
TI - Paravalvular leak after transcatheter aortic valve implantation: is it
anatomically predictable or procedurally determined? MDCT study.
AB - AIM: To investigate the determinants of paravalvular leak (PVL) occurring after
transcatheter aortic valve implantation (TAVI). MATERIALS AND METHODS: One
hundred and eight patients with severe symptomatic aortic stenosis (mean age
75.5+/-11.8 years, 72.2% male) underwent contrast-enhanced electrocardiogram
(ECG)-gated multidetector computed tomography (MDCT) then successful TAVI. The
following parameters were determined in the late systolic phase: annular and left
ventricular outflow tract (LVOT) diameters, annular perimeter, ellipticity index,
annular area, indexed annular area, LVOT perimeter, annulus/LVOT perimeter
difference ratio, the LVOT to ascending aorta angle (< LVOT-AO). In the diastolic
phase, the extent of calcification of the aortic valve (AVC) was assessed
visually and graded semi-quantitatively as grade I, II, and III at the annulus,
LVOT, and aortic cusps levels. Pre-discharge transthoracic echocardiography (TTE)
was performed, and the PVL was graded as grade I, II, and III. The area-dependent
device-annulus sizing ratio was calculated. RESULTS: Absence of PVL was observed
in 44.44% of the patients, 30.56% had grade I PVL, 25% of the patients had grade
II or above, and any PVL was observed in 55.56%. There was no statistically
significant association between the degree of PVL and the extent or the
distribution of AVC, aortic annulus diameters, ellipticity index, annulus/LVOT
perimeter difference ratio or < LVOT-AO. The frequency of PVL was not
significantly different with the use of balloon-expandable or self-expandable
valves. A larger transcatheter heart valve (THV)/annulus sizing ratio was
associated with a lower incidence and degree of PVL (p<0.001); there was no
detectable PVL with a mean sizing ratio of 14.89+/-7.29, and grade I PVL occurred
with a mean sizing ratio 12.43+/-0.84, while PVL of grade II or above occurred
using the mean sizing ratio -0.42+/-5.57. CONCLUSION: The procedure-related
THV/annulus sizing ratio was an important determinant of the degree of PVL after
TAVI, whereas the MDCT-derived anatomical measurements of the aortic root and AVC
were not predictors of PVL.
PMID- 27612849
TI - DPP-4 (CD26) inhibitor sitagliptin exerts anti-inflammatory effects on rat
insulinoma (RINm) cells via suppressing NF-kappaB activation.
AB - Dipeptidyl peptidase-4 (CD26), a cell surface glycoprotein, is expressed by a
variety of cells. It has been shown that dipeptidyl peptidase-4 (CD26) is
involved in T cell activation. Nonetheless, its role in inflammatory effects in
islet beta cells has not been well investigated. In this study, we used
sitagliptin, a classic inhibitor of dipeptidyl peptidase-4 (CD26), to research
the effect of dipeptidyl peptidase-4 (CD26) on the activation of NF-kappaB, the
expression of inflammatory cytokines, and cell apoptosis in rat insulinoma cells.
Results showed that dipeptidyl peptidase-4 (CD26) was expressed on the surface of
rat insulinoma cells. Lipopolysaccharide-induced NF-kappaB activation and
expression of inflammatory cytokines were suppressed by sitagliptin treatment in
rat insulinoma cells. Furthermore, sitagliptin treatment reduced cell apoptosis
stimulated by lipopolysaccharide. Taken together, this study showed for the first
time that sitagliptin suppressed NF-kappaB activation and inflammatory cytokines
expression in rat insulinoma cells, suggesting that the dipeptidyl peptidase-4
inhibitor may exert direct anti-inflammatory effects in islet beta cells.
PMID- 27612850
TI - Bupropion and its photoreactive analog (+/-)-SADU-3-72 interact with luminal and
non-luminal sites at human alpha4beta2 nicotinic acetylcholine receptors.
AB - The interaction of (+/-)-bupropion [(+/-)-BP] with the human (h) alpha4beta2
nicotinic acetylcholine receptor (AChR) was compared to that for its
photoreactive analog (+/-)-2-(N-tert-butylamino)-3'-iodo-4'-azidopropiophenone
[(+/-)-SADU-3-72]. Ca2+ influx results indicated that (+/-)-SADU-3-72 and (+/-)
BP inhibit halpha4beta2 AChRs with practically the same potency. However, (+/-)
SADU-3-72 binds to the [3H]imipramine sites at resting and desensitized
halpha4beta2 AChRs with 3-fold higher affinity compared to that for (+/-)-BP,
which is supported by molecular docking results. The docking results also
indicate that each isomer of BP and SADU-3-72, in the protonated state, interacts
with luminal and non-luminal sites. In the channel lumen, both ligands bind to
two overlapping subsites, one that overlaps the imipramine site, and another much
closer to the cytoplasmic side. The results suggest, for the first time, three
differentiated non-luminal domains, including the transmembrane (TMD),
extracellular (ECD), and ECD-TMD junction. In the ECD-TMD junction, BP and SADU-3
72 bind to overlapping sites. Interestingly, only SADU-3-72 binds to intrasubunit
and intersubunit sites in the TMD, and to additional sites in the ECD. Our
results are consistent with a model where BP and SADU-3-72 bind to overlapping
sites in the luminal and ECD-TMD junctional domains of the halpha4beta2, whereas
only SADU-3-72 binds to additional non-luminal sites. The BP junctional site
opens the door for additional inhibitory mechanisms. The pharmacological
properties of (+/-)-SADU-3-72 showed in this work support further photolabeling
studies to mapping the BP binding sites in the halpha4beta2 AChR.
PMID- 27612847
TI - Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes
Pathogenesis.
AB - The receptor for advanced glycation end products (RAGE) is a novel protein
increasingly studied in the pathogenesis of type 1 diabetes (T1D). RAGE is
expressed by several immune cell types, including T cells, antigen-presenting
cells, endothelial cells, and the endocrine cells of the pancreatic islets. RAGE
binds various ligands including advanced glycation end products (AGEs), high
mobility group box protein 1 (HMGB1), S100 proteins, beta-amyloid, beta-sheet
fibrils, and lipopolysaccharide. AGEs are a particularly interesting ligand
because their exogenous introduction into the body can be accelerated by the
consumption of AGE-rich processed foods. This review will detail RAGE isoforms
and its ligands and discuss how RAGE binding on the aforementioned cells could be
linked to T1D pathogenesis.
PMID- 27612851
TI - Systematic review of motor evoked potentials monitoring during thoracic and
thoracoabdominal aortic aneurysm open repair surgery: a diagnostic meta-analysis.
AB - Motor evoked potential (MEP) monitoring has been used to prevent neurological
complications such as paraplegia in patients who underwent thoracic or
thoracoabdominal aortic aneurysm (TAA/TAAA) surgery. The object of this study was
making a systematic review to survey the performance of MEP monitoring during
TAA/TAAA open repair surgery. We searched electronic databases for relevant
studies. We summarized the diagnostic data with summary sensitivity, summary
specificity and forest plots of pooled sensitivity, and conducted sub-group
analysis. The quality of the studies was assessed using the Quality Assessment of
Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We also surveyed the reporting
rate of clinical key factors such as methods of anesthesia, surgery, and success
rate of MEP. Nineteen studies met our criteria. The results of meta-analysis
showed 89.1 % summary sensitivity (95 % confidence interval 47.9-98.6 %) and 99.3
% summary specificity (95 % confidence interval 96.1-99.9 %). Sub-group analysis
of pooled sensitivity and specificity by all-or-none cut-off point were better
than other cut-off points. The results of the QUADAS-2 were not good. The
performance of MEP monitoring was good for detecting postoperative paraplegia in
TAA/TAAA open repair surgery. The cut-off point of all-or-none may be the best,
according to our review.
PMID- 27612852
TI - Peripheral nerve conduction abnormalities precede morphological alterations in an
experimental rat model of sepsis.
AB - PURPOSE: The pathological mechanisms of critical illness polyneuropathy (CIP), an
acute neuromuscular disorder, remain unknown. In this study, we evaluated nerve
and vascular properties that might account for electrophysiological
abnormalities, including reduced nerve conduction amplitude, in the early phase
of CIP. METHODS: Rats were administered intravenous saline (C-group; n = 31) or
lipopolysaccharide (3 mg/kg/day; L-group; n = 30) for 48 h. Subsequently,
tracheotomy was performed and sciatic nerves exposed bilaterally. A catheter was
inserted into the left internal carotid artery to measure the mean arterial
pressure (MAP). Nerve conduction velocity (NCV), nerve blood flow (NBF), evoked
amplitudes, chronaxie, rheobase, and the absolute refractory period (ARP) were
measured from the sciatic nerves. Degeneration, myelination, and neutrophil
infiltration were examined in the sciatic nerves using histology and electron
microscopy. RESULTS: The NBF (C-group 25 +/- 3 ml/100 g/min, L-group 13 +/- 3
ml/100 g/min, p < 0.001) was lower in the L-group, but the MAP was similar
between groups (C-group 119 +/- 17 mmHg, L-group 115 +/- 18 mmHg, p = 0.773). LPS
also caused a severe reduction in amplitude (C-group 0.9 +/- 0.2 mV, L-group 0.2
+/- 0.1 mV, p < 0.001), while latency and NCV were not affected. Of note,
response amplitudes partially recovered with an increase in stimulus intensity.
LPS treatment increased the rheobase and decreased the chronaxie (rheobase: C vs
L-group; 0.35 +/- 0.07 vs 1.29 +/- 0.66 mA, p < 0.001; chronaxie 171 +/- 24 vs 42
+/- 20 us, p < 0.001), while ARP was unchanged. No primary axonal degeneration or
inflammatory infiltration was observed. CONCLUSIONS: Our findings suggest that
primary electrophysiological deterioration is due to threshold alterations rather
than morphological alterations after 48 h of LPS treatment.
PMID- 27612853
TI - Look Who's Talking. Explaining Water-Related Information Sharing and Demand for
Action Among Ugandan Villagers.
AB - Many national water policies propagate community-based participatory approaches
to overcome weaknesses in supply-driven rural water provision, operation, and
maintenance. Citizen involvement is thought to stimulate bottom-up accountability
and broaden the information base, which may enrich design and implementation
processes and foster improved water accessibility and sustainability. Practices
on the ground, however, are embedded in socio-political realities which mediate
possible beneficial effects of participatory approaches. This paper builds on
full social network data collected in a Ugandan village to study the social and
political reality of two distinct levels of participation, i.e. local information
sharing among citizens and a more active appeal to fellow citizens to improve
water services. We use Logistic Regression Quadratic Assignment Procedure to
explore what type of actor and network traits influence information sharing and
whether the same factors are in play in the demand for action to remedy water
related problems. Whereas social aspects (social support relations) and homophily
(using the same water source, the same gender) play an important role in
information sharing, it is the educational level, in particular, of the villager
who is called upon that is important when villagers demand action. Our findings
also demonstrate that those most in need of safe water do not mobilize their
information sharing ties to demand for action. This indicates that building local
water policies and practice exclusively on locally existing demand for action may
fail to capture the needs of the most deprived citizens.
PMID- 27612854
TI - Effects of Vocabulary and Phonotactic Probability on 2-Year-Olds' Nonword
Repetition.
AB - This study investigates the relationship between nonword repetition (NWR) and
vocabulary in 2-year-olds. Questions addressed are whether (1) NWR and vocabulary
are associated, (2) phonotactic probability affects NWR, and (3) there is an
interaction effect between phonotactic probability and vocabulary on NWR
performance. The general aim of the study is to investigate whether NWR, as a
task of phonological storage, assesses the quality of phonological
representations in children as young as 2 years of age. 557 Dutch 2-year-olds
performed a NWR task containing items of varying phonotactic probability as well
as a receptive vocabulary task. The results showed a moderate, significant
correlation between NWR and vocabulary. Phonotactic probability had an effect on
NWR performance. Further analyses showed that there was a significant interaction
between phonotactic probability and vocabulary for part of the items. These
results support previously reported effects of vocabulary and phonotactic
probability on NWR in older, English-speaking children for a large sample of
Dutch-speaking 2-year-olds, and provide evidence that NWR assesses the quality of
phonological representations already in very young children.
PMID- 27612855
TI - Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced
diabetic nephropathy in female rats.
AB - Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever
larger health burden worldwide, more effective therapies are desperately needed.
In the present study, the anti-diabetic and renoprotective effects of aliskiren
have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by
a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats
were divided into four groups; normal, diabetic, diabetic treated with gliclazide
(10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day)
for 1 month. At the end of the experiment, mean arterial blood pressure and heart
rate were recorded. Rats were then euthanized and serum was separated for
determination of glucose, insulin, kidney function tests, superoxide dismutase
activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-alpha). One
kidney was used for estimation of malondialdehyde (MDA), reduced glutathione
(GSH), and nitric oxide (NO) contents. Other kidney was used for
histopathological study and immunohistochemical measurement of caspase-3 and
transforming growth factor beta (TGF-beta). In addition, islets of Langerhans
were isolated from normal rats by collagenase digestion technique for in vitro
study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level
both in vivo and in vitro, normalized kidney function tests and blood pressure,
and alleviated STZ-induced kidney histopathological changes. This could be
related to the ability of aliskiren toward preserving hemodynamic changes and
alleviating oxidative stress and inflammatory and apoptotic markers induced by
STZ in rats. However, aliskiren was more effective than gliclazide in relieving
STZ-induced DN. These findings support the beneficial effect of aliskiren
treatment in DN which could be attributed to its anti-diabetic, renoprotective,
antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical
studies are required to establish the effectiveness of aliskiren treatment in
patients suffering from hypertension and diabetes.
PMID- 27612858
TI - Triple-Negative Breast Cancer: A Comprehensive Study of Clinical,
Histomorphological, and Immunohistochemical Features in Indian Patients.
AB - Triple-negative breast cancers (TNBCs) are characterized by negative expression
for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2)
receptors. Although the majority of basal-like breast cancers (BLBCs) diagnosed
based on gene expression profiling belong to the TNBC group, both entities are
not synonymous. Core BLBCs are TNBCs, which are positive for basal cytokeratin
(CK) and/or epidermal growth factor receptor (EGFR). We aimed to study and
correlate a TNBC cohort for various histomorphological features and
immunohistochemical (IHC) profile in Indian patients. We studied 205 naive TNBCs
for histopathological features, which were further evaluated for basal CKs
namely, CK5/6, CK14, CK17-and EGFR expression to classify them as core BLBCs,
using criteria of any basal CK and/or EGFR positivity and 7-negative phenotype
(7NP). Among 205 TNBCs, 91% of cases were core BLBCs, and absence of ductal
carcinoma in situ (DCIS) was significantly associated ( P = .014) with core BLBC.
Geographic necrosis was correlated with expression of CK17 ( P = .002) and EGFR (
P = .038). A ribbon-like trabecular pattern and absence of DCIS were associated
with CK17 ( P = .0002 and P = .043, respectively) and CK14 ( P = .04 and P =
.0008, respectively). TNBC is a heterogeneous subgroup with adverse
clinicopathological features, and many of them show significant correlation with
basal CKs. TNBCs cannot be classified as core BLBC or 7NP based on morphological
features, except absence of DCIS. However, this study illustrates the
heterogeneity in TNBCs on the basis of IHC markers.
PMID- 27612856
TI - Mesothelial cells interact with tumor cells for the formation of ovarian cancer
multicellular spheroids in peritoneal effusions.
AB - Epithelial ovarian cancer (EOC) dissemination is primarily mediated by the
shedding of tumor cells from the primary site into ascites where they form
multicellular spheroids that rapidly lead to peritoneal carcinomatosis. While the
clinical importance and fundamental role of multicellular spheroids in EOC is
increasingly appreciated, the mechanisms that regulate their formation and
dictate their cellular composition remain poorly characterized. To investigate
these important questions, we characterized spheroids isolated from ascites of
women with EOC. We found that in these spheroids, a core of mesothelial cells was
encased in a shell of tumor cells. Analysis further revealed that EOC spheroids
are dynamic structures of proliferating, non-proliferating and hypoxic regions.
To recapitulate these in vivo findings, we developed a three-dimensional co
culture model of primary EOC and mesothelial cells. Our analysis indicated that,
compared to the OVCAR3 cell line, primary EOC cells isolated from ascites as well
as mesothelial cells formed compact spheroids. Analysis of heterotypic spheroid
microarchitecture revealed a structure that grossly resembles the structure of
spheroids isolated from ascites. Cells that formed compact spheroids had elevated
expression of beta1 integrin and low expression of E-cadherin. Addition of beta1
integrin blocking antibody or siRNA-mediated downregulation of beta1 integrin
resulted in reduced tightness of the spheroids. Interestingly, the loss of MUC16
and E-cadherin expression resulted in the formation of more compact spheroids.
Therefore, our findings support the heterotypic nature of spheroids from
malignant EOC ascites. In addition, our data describe an unusual link between E
cadherin expression and less compact spheroids. Our data also emphasize the role
of MUC16 and beta1 integrin in EOC spheroid formation.
PMID- 27612859
TI - Effect of an unrelated fluent action on word recognition: A case of motor
discrepancy.
AB - It is now well established that motor fluency affects cognitive processes,
including memory. In two experiments participants learned a list of words and
then performed a recognition task. The original feature of our procedure is that
before judging the words they had to perform a fluent gesture (i.e., typing a
letter dyad). The dyads comprised letters located on either the right or left
side of the keyboard. Participants typed dyads with their right or left index
finger; the required movement was either very small (dyad composed of adjacent
letters, Experiment 1) or slightly larger (dyad composed of letters separated by
one key, experiment 2). The results show that when the gesture was performed in
the ipsilateral space the probability of recognizing a word increased (to a
lesser extent it is the same with the dominant hand, experiment 2). Moreover, a
binary regression logistic highlighted that the probability of recognizing a word
was proportional to the speed by which the gesture was performed. These results
are discussed in terms of a feeling of familiarity emerging from motor
discrepancy.
PMID- 27612857
TI - Neurochemical evidence supporting dopamine D1-D2 receptor heteromers in the
striatum of the long-tailed macaque: changes following dopaminergic manipulation.
AB - Although it has long been widely accepted that dopamine receptor types D1 and D2
form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers
has been recently challenged. In an attempt to properly characterize D1-D2
receptor heteromers, here we have used the in situ proximity ligation assay (PLA)
in striatal sections comprising the caudate nucleus, the putamen and the core and
shell territories of the nucleus accumbens. Experiments were carried out in
control macaques as well as in MPTP-treated animals (with and without
dyskinesia). Obtained data support the presence of D1-D2 receptor heteromers
within all the striatal subdivisions, with the highest abundance in the accumbens
shell. Dopamine depletion by MPTP resulted in an increase of D1-D2 density in
caudate and putamen which was normalized by levodopa treatment. Two different
sizes of heteromers were consistently found, thus suggesting that besides
individual heteromers, D1-D2 receptor heteromers are sometimes organized in
macromolecular complexes made of a number of D1-D2 heteromers. Furthermore, the
PLA technique was combined with different neuronal markers to properly
characterize the identities of striatal neurons expressing D1-D2 heteromers. We
have found that striatal projection neurons giving rise to either the direct or
the indirect basal ganglia pathways expressed D1-D2 heteromers. Interestingly,
macromolecular complexes of D1-D2 heteromers were only found within cholinergic
interneurons. In summary, here we provide overwhelming proof that D1 and D2
receptors form heteromeric complexes in the macaque striatum, thus representing a
very appealing target for a number of brain diseases involving dopamine
dysfunction.
PMID- 27612860
TI - Implicit associative learning in synesthetes and nonsynesthetes.
AB - Although cross-modal neural connections and genetic underpinnings are prominent
in most current theories regarding the development of synesthesia, the potential
role of associative learning in the formation of synesthetic associations has
recently been revitalized. In this study, we investigated implicit associative
learning in synesthetes and nonsynesthetes by recording reaction times to a
target whose color was probabilistically correlated with its shape. A continuous
measure of target detection at multiple time points during learning revealed that
synesthetes and nonsynesthetes learn associations differently. Specifically, our
results demonstrated a "fast-facilitation" learning effect for nonsynesthetes and
a "fast-interference, slow-facilitation" learning effect for synesthetes.
Additionally, synesthetes exhibited superior long-term memory for the learned
associations in a surprise delayed retest. After this retest, participants
implicitly learned new (shuffled) shape-color associations. We found that
synesthetes experienced greater interference while learning these new shape-color
associations. These results detail ways in which implicit associative learning
and memory differ between synesthetes and nonsynesthetes.
PMID- 27612861
TI - Non-cognate translation priming in masked priming lexical decision experiments: A
meta-analysis.
AB - The masked translation priming paradigm has been widely used in the last 25 years
to investigate word processing in bilinguals. Motivated by studies reporting
mixed findings, in particular for second language (L2) to first language (L1)
translation priming, we conducted, for the first time in the literature, a meta
analysis of 64 masked priming lexical decision experiments across 24 studies to
assess the effect sizes of L1-L2 and L2-L1 non-cognate translation priming
effects in bilinguals. Our meta-analysis also investigated the influence of
potential moderators of translation priming effects. The results provided clear
evidence of significant translation priming effects for both directions, with L1
L2 translation priming significantly larger than L2-L1 translation priming (i.e.,
effect size of 0.86 vs. 0.31). The analyses also revealed that L1-L2 translation
effect sizes were moderated by the interval between prime and target (ISI),
whereas L2-L1 translation effect sizes were modulated by the number of items per
cell. Theoretical and methodological implications of this meta-analysis are
discussed and recommendations for future studies are provided.
PMID- 27612862
TI - Linked linear mixed models: A joint analysis of fixation locations and fixation
durations in natural reading.
AB - The complexity of eye-movement control during reading allows measurement of many
dependent variables, the most prominent ones being fixation durations and their
locations in words. In current practice, either variable may serve as dependent
variable or covariate for the other in linear mixed models (LMMs) featuring also
psycholinguistic covariates of word recognition and sentence comprehension.
Rather than analyzing fixation location and duration with separate LMMs, we
propose linking the two according to their sequential dependency. Specifically,
we include predicted fixation location (estimated in the first LMM from
psycholinguistic covariates) and its associated residual fixation location as
covariates in the second, fixation-duration LMM. This linked LMM affords a
distinction between direct and indirect effects (mediated through fixation
location) of psycholinguistic covariates on fixation durations. Results confirm
the robustness of distributed processing in the perceptual span. They also offer
a resolution of the paradox of the inverted optimal viewing position (IOVP)
effect (i.e., longer fixation durations in the center than at the beginning and
end of words) although the opposite (i.e., an OVP effect) is predicted from
default assumptions of psycholinguistic processing efficiency: The IOVP effect in
fixation durations is due to the residual fixation-location covariate, presumably
driven primarily by saccadic error, and the OVP effect (at least the left part of
it) is uncovered with the predicted fixation-location covariate, capturing the
indirect effects of psycholinguistic covariates. We expect that linked LMMs will
be useful for the analysis of other dynamically related multiple outcomes, a
conundrum of most psychonomic research.
PMID- 27612863
TI - Ultrafast spectroscopy tracks carotenoid configurations in the orange and red
carotenoid proteins from cyanobacteria.
AB - A quenching mechanism mediated by the orange carotenoid protein (OCP) is one of
the ways cyanobacteria protect themselves against photooxidative stress. Here, we
present a femtosecond spectroscopic study comparing OCP and RCP (red carotenoid
protein) samples binding different carotenoids. We confirmed significant changes
in carotenoid configuration upon OCP activation reported by Leverenz et al.
(Science 348:1463-1466. doi: 10.1126/science.aaa7234 , 2015) by comparing the
transient spectra of OCP and RCP. The most important marker of these changes was
the magnitude of the transient signal associated with the carotenoid
intramolecular charge-transfer (ICT) state. While OCP with canthaxanthin
exhibited a weak ICT signal, it increased significantly for canthaxanthin bound
to RCP. On the contrary, a strong ICT signal was recorded in OCP binding
echinenone excited at the red edge of the absorption spectrum. Because the
carbonyl oxygen responsible for the appearance of the ICT signal is located at
the end rings of both carotenoids, the magnitude of the ICT signal can be used to
estimate the torsion angles of the end rings. Application of two different
excitation wavelengths to study OCP demonstrated that the OCP sample contains two
spectroscopically distinct populations, none of which is corresponding to the
photoactivated product of OCP.
PMID- 27612864
TI - [CHAOS in neonatal emergency care? : Tracheal agenesis in the obstetric theatre].
AB - Tracheal agenesis (TA) is a very rare congenital malformation of unknown
aetiology. It is often associated with polymalformative syndromes; the neonates
commonly present a critical condition during post-natal treatment. Pathology
revolves around the triad of aphonia, respiratory distress syndrome and
impossibility of endotracheal intubation. In contrast to the most important
differential diagnosis, i. e., congenital high airway obstruction syndrome
(CHAOS), surgical airway management is also impossible due to the absence of
tracheal structures. In most cases, prognosis is very poor. The case report at
hand portrays the treatment of a neonate suffering from tracheal agenesis.
PMID- 27612866
TI - F-box gene FOA2 regulates GA- and ABA- mediated seed germination in Arabidopsis.
PMID- 27612867
TI - US drug industry group launches campaign to defend pricing.
PMID- 27612865
TI - [Hemophagocytic lymphohistiocytosis : A diagnostic challenge on the ICU].
AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) has well been studied as a
genetic disorder in children (primary HLH). Mutations in the regulatory complex
of the cellular immune synapse lead to a loss of function of cytotoxic T-cells
and natural killer cells with excessive inflammation based on a cytokine storm.
During the last decade, an increasing number of adult HLH patients without a
family history of HLH (secondary or acquired HLH) have been reported. Various
triggers - infections, malignancies or autoimmune diseases - result in an
acquired loss of function of these cells and a sepsis-like disease. Missed or
late diagnosis is believed to be a major cause of the high mortality. OBJECTIVES:
To describe the current knowledge on HLH and to raise awareness. MATERIALS AND
METHODS: Analysis of case reports, current studies, and expert recommendations.
RESULTS: Increased vigilance in identifying the adult form of HLH resulted in an
increasing number of case reports over the past few years. HLH patients typically
present with a clinical phenotype resembling severe sepsis or septic shock with
fever, cytopenia, and organomegaly, which do not or insufficiently respond to
anti-infective treatment. Early recognition of HLH distinction from sepsis, and
prompt initiation of treatment - which is fundamentally different from sepsis -
are crucial for improved outcome. A promising diagnostic parameter is ferritin,
which has gained sufficient specificity, but only in the context of the triad of
fever, cytopenia, and organomegaly. Treatment of adult HLH patients requires
immunosuppression, with strict therapeutic guidance derived from the triggering
disease. CONCLUSIONS: Because of the similar clinical presentation to that of
sepsis, HLH is often not recognized, resulting in a fatal outcome. In "sepsis"
patients on the ICU with deterioration despite a standard of care, HLH needs to
be considered by testing for ferritin when considering differential diagnoses.
The complexity of the illness requires interdisciplinary patient care with
specific integration of the hematologist in the diagnostic workup and therapeutic
management, because of the frequent use of chemotherapy-based immunosuppression.
PMID- 27612868
TI - A case of surgery for congenital esophagobronchial fistula accompanied by a
destroyed lung.
AB - Congenital esophagobronchial fistula (EBF) is rarely seen in adults. We report a
case of EBF detected in adulthood with a destroyed lung. A 67-year-old man
experienced repeated pneumonia during his childhood. Since the age of 38, he had
often suffered from bloody phlegm and always had a cough and sputum during oral
intake. Before cardiac surgery for atrial fibrillation and valvular disease,
computed tomography (CT) detected bronchiectasis, which could cause pulmonary
bleeding during heart surgery, and the patient was introduced to our hospital for
lung resection. A fistula between the esophagus and the right lower lung lobe was
found using CT, esophagoscopy, and esophagography. Contrast CT and angiography
revealed an abnormal artery branching from the inferior phrenic artery into the
lobe. As indicated by intraoperative findings, the middle and lower lobes had
strongly adhered to chest wall and diaphragm, but we located the fistula easily
without adhesion to the surroundings, severed it using an automatic stapler, and
resected the middle and lower lobes. The symptoms disappeared immediately, and
the patient was uneventfully discharged.The diagnosis of congenital EBF was
established with intraoperative findings and pathological exam. The existence of
pulmonary sequestration was suggested because of the long-term absence of any
symptoms during his adulthood, the tract of the EBF running into the lung, not
directly into the bronchus, and a septum pathologically detected in the right
lower lobe. A congenital EBF should be considered for differential diagnosis in
cases of limited bronchiectasis in elderly people.
PMID- 27612869
TI - Intrahepatic cholangiocarcinoma coinciding with a liver metastasis from a rectal
carcinoma: a case report.
AB - BACKGROUND: We experience many cases of liver metastasis from colorectal cancer,
but synchronous occurrence of intrahepatic cholangiocarcinoma (ICC) and liver
metastasis from a rectal cancer is extremely rare. We herein report a case of ICC
coinciding with a liver metastasis from a known rectal carcinoma. CASE
PRESENTATION: A 68-year-old man was referred to our hospital for investigation of
multiple liver tumors. Total colonoscopy and computed tomography (CT) revealed a
rectal carcinoma, coinciding with liver metastasis. He was planned to receive
chemotherapy following rectal resection. During chemotherapy for the rectal
cancer, one of the liver tumors gradually grew after first shrinking. The
following hepatectomy revealed the presence of intrahepatic cholangiocarcinoma
(ICC). Despite intensive chemotherapy for the ICC, he passed away 6 months after
the hepatectomy. CONCLUSIONS: We should also suspect the possibility of multiple
primary cancers, even if the patient has a history of cancer that is likely to
cause metastatic lesions. When simultaneous neoplasms are diagnosed, systematic
treatment should be targeted to the tumor with the worst prognosis.
PMID- 27612870
TI - Follow-up of asymptomatic adult diaphragmatic hernia: should patients with this
condition undergo immediate operation? A report of two cases.
AB - BACKGROUND: Asymptomatic diaphragmatic hernia is generally thought to be rare
among adults. We present two different types of asymptomatic diaphragmatic hernia
diagnosed with computed tomography (CT) and discuss treatment strategies. CASE
PRESENTATION: Case 1: A 37-year-old woman was diagnosed with catamenial
pneumothorax in the right diaphragm. Partial resection of the diaphragm and lung
was performed using a linear stapler. She was asymptomatic after the operation
and gave birth 2 years later. After delivery, she experienced recurrent
pneumothorax, and CT revealed a right diaphragmatic defect with herniation of a
part of the liver into the thorax. An iatrogenic diaphragmatic hernia was
diagnosed. There has been no change in the size of the hernia and no symptoms due
to the diaphragmatic hernia for more than 3 years after it was diagnosed. Case 2:
A 75-year-old woman was previously diagnosed with rectal cancer and had undergone
surgery after chemoradiotherapy. One year after surgery, herniation of a 3 * 1.3
cm section of retroperitoneal fat tissue into the left thoracic cavity was
observed incidentally at a follow-up CT and was diagnosed as an adult Bochdalek
hernia (BH). We reviewed the patient's past CT findings and confirmed that the
same finding had been present since the first scan. A wait-and-see approach was
chosen because there had been no change in the size of hernia, there were no
symptoms, the patient was elderly, and there was a high risk of recurrence of the
rectal cancer. She has had no symptoms to date, and careful follow-up has been
performed. CONCLUSIONS: There are few reports of asymptomatic adult diaphragmatic
hernia. Although symptomatic diaphragmatic hernia is generally treated
surgically, there are cases in which a wait-and-see approach has been applied,
such as our asymptomatic cases.
PMID- 27612871
TI - Sonographic Features of Endobronchial Ultrasound in Differentiation of Benign
Lymph Nodes.
AB - Endobronchial ultrasound (EBUS) features have been found to be a useful tool in
differentiating malignant from benign lymph nodes, but the use of these features
to distinguish benign intrathoracic lymphadenopathies, including tuberculosis,
sarcoidosis and reactive lymphadenitis, has not been established. The goal of
this study was to evaluate the use of EBUS features in predicting tuberculosis,
sarcoidosis, and non-specific inflammation. One hundred eighty-eight patients
with suspected benign lymphadenopathy were included in the study. The EBUS
features studied were short axis, shape, calcification, central hilar structure,
necrosis sign, margins, echogenicity, clustered formation and vascular patterns.
The sonographic findings were confirmed by clinicopathologic results. EBUS-Guided
transbronchial needle aspiration was performed on 452 lymph nodes. Thirty-seven
tuberculous nodes, 193 sarcoid nodes and 150 reactive nodes were retrospectively
analyzed. Excluded were 72 nodes. Multivariate analysis revealed that presence of
the necrosis sign and absence of the clustered formation are independent factors
predictive of tuberculous nodes. Short axis >1 cm, absence of central hilar
structure, distinct margins, presence of clustered formation and non-hilar
perfusion were predictive of sarcoid nodes. Presence of central hilar structure,
absence of clustered formation and vascular pattern (hilar perfusion or
avascularity) were predictive of reactive lymphadenitis. The sum score model of
these combined predictive factors indicated that the best diagnostic accuracies
for predicting tuberculous nodes, sarcoid nodes and reactive lymphadenitis were
77.1%, 89.2% and 87.1%, respectively. Sonographic features could be helpful in
differentiating the type of benign intrathoracic lymphadenopathy during EBUS
examination.
PMID- 27612873
TI - Rumours about wildlife pest introductions: European rabbits in Spain.
AB - Rumours associated with wildlife are frequent, although they have received little
attention in the scientific literature. Studying rumours is important because of
their relevance not only in a broad theoretical sense but also in environmental
management. The goal of this study is to explore the complexity of the
relationships between humans and wildlife through a thematic analysis of rumours
associated with allegedly introduced European rabbits (Oryctolagus cuniculus)
that cause crop damage in Spain. For this purpose, potential rumours were
identified using the Google search engine. Data analysis consisted of reading and
re-reading Web-based texts to identify main themes, ideas and topics with the
assistance of NVivo 10 software. The analysis identified three main themes: (1)
the reviewed websites referred to allegedly introduced rabbits which differed
from native rabbits; (2) differences were based on alleged observations of
unnatural behaviour, physiology or physical appearance of introduced rabbits; (3)
rumours were frequently used in the context of the rabbit management conflict;
e.g. farmers accused hunters of releasing harmful rabbits. This study suggests
that the analysis of wildlife-release rumours sheds light on the position of
parties involved in conflicts associated with the (alleged) introduction of
wildlife species. It stresses the importance of rumours in conservation and
environmental management, and opens the door to future research.
PMID- 27612872
TI - An association between sperm PLCzeta levels and varicocele?
AB - PURPOSE: We aimed to compare the expression of phospholipase C zeta (PLCzeta), as
one of the main sperm factors involved in oocyte activation, at both RNA and
protein levels in fertile men and those with varicocele. METHODS: This study
included 35 individuals with male factor infertility presenting primary
infertility with grade II and III unilateral varicocele and 20 fertile men
without varicocele. Semen parameters were assessed according to WHO 2010. Sperm
DNA fragmentation, relative expression of PLCzeta at messenger RNA, and protein
levels were evaluated by sperm chromatin structure assay (SCSA), real-time PCR,
and Western blot analysis, respectively. RESULTS: The results of this study
reveal that the mean relative expression of PLCzeta was significantly lower in
individuals with varicocele compared to fertile men at both transcription and
translation levels. In addition, the percentage of DNA fragmentation was
significantly higher in infertile men with varicocele compared to fertile men.
CONCLUSIONS: The findings of the present study illustrate that one of the
etiologies of reduced fertility associated with varicocele is the low expression
of PLCzeta. This effect could subsequently reduce the sperm ability to induce
oocyte activation. Therefore, these results hold promise to modify our
understanding of reproductive physiology of varicocele state.
PMID- 27612874
TI - Corticotropin-Releasing Factor Receptors and Their Interacting Proteins:
Functional Consequences.
AB - The corticotropin-releasing factor (CRF) system, which is involved in stress,
addiction, and anxiety disorders such as depression, acts through G-protein
coupled receptors (GPCRs) known as type-1 and type-2 CRF receptors. The purpose
of this review is to highlight recent advances in the interactions of CRF
receptors with other GPCRs and non-GPCR proteins and their associated functional
consequences. A better understanding of these interactions may generate new
pharmacological alternatives for the treatment of addiction and stress-related
disorders.
PMID- 27612875
TI - Diet quality and academic achievement: a prospective study among primary school
children.
AB - PURPOSE: Poor diet quality may impair academic achievement in children, but such
evidence is limited. Therefore, we investigated the associations of healthy diet
in Grade 1 assessed by Mediterranean Diet Score (MDS), Baltic Sea Diet Score
(BSDS), and Finnish Children Healthy Eating Index (FCHEI) with academic
achievement in Grades 1-3 in children. METHODS: The participants were 161 Finnish
children who were 6-8 years old in Grade 1 and attended in a large ongoing
physical activity and dietary intervention study. Dietary factors were assessed
using 4-day food records, and MDS, BSDS, and FCHEI were calculated. Academic
achievement was assessed by reading fluency, reading comprehension, and
arithmetic skill tests. The data were analyzed using linear regression analysis
and analysis of covariance adjusted for age, sex, parental education, household
income, body fat percentage, physical activity, the PANIC Study group, and total
energy intake. RESULTS: MDS was positively associated with reading comprehension
in Grade 3 (standardized regression coefficient beta = 0.167, P = 0.032). BSDS
was positively associated with reading fluency in Grades 2-3 and reading
comprehension in Grades 1-3 (beta = 0.161-0.274, P < 0.05). FCHEI was positively
related to reading fluency in Grades 1-2 and reading comprehension in Grades 1-3
(beta = 0.190-0.344, P < 0.05). Children in the highest third of BSDS and FCHEI
had better reading fluency and reading comprehension in Grades 1-3 than children
in the lowest third (P < 0.05). None of the diet scores was associated with
arithmetic skills. CONCLUSIONS: Healthier diet assessed by BSDS or FCHEI in Grade
1 was associated with better reading skills, but not with arithmetic skills,
among children in Grades 1-3. Long-term intervention studies are needed to
investigate the effects of improvements in diet quality on academic achievement
among children. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
NCT01803776.
PMID- 27612876
TI - Effects of low-glycemic-index diets in pregnancy on maternal and newborn outcomes
in pregnant women: a meta-analysis of randomized controlled trials.
AB - PURPOSE: Maternal diet with a high glycemic index (GI) is associated with fetal
overgrowth and higher infant body adiposity. Effects of low-GI diet on maternal
and newborn outcomes have been assessed in both healthy pregnancy and gestational
diabetes mellitus, but the results remain inconclusive. This meta-analysis aimed
to examine the effects of low-GI diets on maternal and newborn outcomes. METHODS:
PubMed, Clinical Trials, and Cochrane Library databases were searched for
relevant randomized trials up to January 2016. Random- or fixed-effects models
were used to calculate combined treatment effects. RESULTS: A total of 11 trials
involving 1985 women were eligible for analysis. This meta-analysis assessed 7
maternal and 11 newborn outcomes. Of these, gestational weight gain (GWG),
fasting blood glucose (FBG), newborn birth weight, ponderal index (PI),
proportion of macrosomia, and large for gestational age (LGA) were investigated
in more than 8 trials. Compared with control diets, low-GI diets significantly
reduced FBG (weight mean differences (WMD) = -0.18 mmol/L, 95 % CI: -0.33,
0.02), 2-h postprandial glucose level (WMD = -0.33 mmol/L, 95 % CI: -0.54,
0.12), and the proportion of LGA (RR = 0.52, 95 % CI: 0.31, 0.89). A lower GWG
(WMD = -0.69 kg, 95 % CI: -1.74, 0.36) and birth weight (WMD = -0.10 kg, 95 % CI:
-0.23, 0.03) were also observed without significant differences. Heterogeneity
was observed in the GWG, FBG, and birth weight analyses. Low-GI diets did not
affect other maternal and newborn outcomes. In subgroup and sensitivity analyses,
the intervention effects of low GI on GWG and FBG varied. CONCLUSIONS: Low-GI
diets may have beneficial effects on maternal outcomes for those at risk of
developing high glucose levels, without causing adverse effects on newborn
outcomes. However, results should be interpreted with caution because of the
evidence of heterogeneity and limited number of studies.
PMID- 27612878
TI - Cumulative Risk on the Oxytocin Receptor Gene (OXTR) Predicts Empathic
Communication by Physician Assistant Students.
AB - In the relationship between patients and health care providers, few communicative
features are as significant as the providers' ability to express empathy. A
robust empirical literature describes the importance of physician communication
skills-particularly those that convey empathy-yet few studies have examined
empathic communication by physician assistants, who provide primary care for an
increasing number of Americans. The present study examines the empathic
communication of physician assistant students in interactions with standardized
patients. Over a 6-month period, each student conducted three clinical
interviews, each of which was evaluated for empathic communication by the
patients, the students' clinical instructors, and third-party observers. Students
also provided saliva samples for genotyping six single-nucleotide polymorphisms
on the oxytocin receptor gene (OXTR) that are linked empirically to empathic
behavior. Consistent with recent research, this study adopted a cumulative risk
approach wherein students were scored for their number of risky alleles on the
single-nucleotide polymorphisms. Results indicated that cumulative risk on OXTR
receptor gene predicted lower patient empathy scores as rated by instructors and
observers, but not by standardized patients.
PMID- 27612879
TI - Lipoprotein profiles of hepatic cell lines at various stages of differentiation.
AB - We studied the lipoprotein profiles of human hepatic cells at various stages of
differentiation. The production of three major classes of lipoproteins, very low
density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density
lipoprotein (HDL), was detected in three well-differentiated human hepatoma cell
lines and primary human hepatocytes; however, these lipoproteins were not
detected in the culture medium in which undifferentiated hepatoma cell lines were
grown. Reverse transcription polymerase chain reaction analysis demonstrated that
the expression levels of apolipoprotein A1 (ApoA1), ApoB100, and microsomal
triglyceride transfer protein (MTP) were markedly lower in the undifferentiated
hepatoma cell lines than in the well-differentiated hepatoma cell lines and
primary hepatocytes. These results indicate that apolipoprotein synthesis, and
triglyceride-transport by MTP might be rate-limiting steps in lipoprotein
production in mature hepatic cells.
PMID- 27612877
TI - Lipid profile status and other related factors in patients with
Hyperphenylalaninaemia.
AB - BACKGROUND: The mainstay of treating patients with phenylketonuria (PKU) is based
on a Phe-restricted diet, restrictive in natural protein combined with Phe-free L
amino acid supplements and low protein foods. This PKU diet seems to reduce
atherogenesis and confer protection against cardiovascular diseases but the
results from the few published studies have been inconclusive. The aim of our
study was to evaluate the relationship between the lipid profile and several
treatment-related risk factors in patients with hyperphenylalaninaemia (HPA) in
order to optimize their monitoring. METHODS: We conducted a cross-sectional
multicentre study. A total of 141 patients with HPA were classified according to
age, phenotype, type of treatment and dietary adherence. Annual median blood
phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, blood
pressure (BP) and biochemical parameters [(triglycerides, total cholesterol (TC),
high-density lipoprotein cholesterol (HDL-C), low density lipoprotein-cholesterol
(LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB), vitamin B12, total
homocysteine (tHcy), Methionine (Met), high sensitivity C-Reactive Protein
(hsCRP)] were collected for each patient. RESULTS: Plasma TC levels were lower in
patients with PKU than in the mild-HPA group (150 +/- 31 vs. 164 +/- 22 mg/dL),
and there was a weak inverse correlation between plasma TC and Phe levels. HDL-C,
LDL-C, ApoA and ApoB levels were lower in the PKU group than in mild-HPA.
Patients with PKU had higher systolic BP than the mild-HPA group and there was
found a quadratic correlation between median Phe levels and systolic BP (p =
6.42e(-5)) and a linear correlation between median Phe levels and diastolic BP (p
= 5.65e(-4)). In overweight or obese PKU patients (24.11 %), biochemical
parameters such as TC, triglycerides, LDL-C, tHcy, hsCRP and BP were higher. By
contrast, HDL-C was lower in these patients. CONCLUSION: Our data show a direct
correlation between lipid profile parameters and good adherence to the diet in
PKU patients. However, lipid profile in overweight or obese patients displayed an
atherogenic profile, in addition to higher hsCRP concentrations and BP. Our study
contributes to a better understanding of the relationship between phenotype and
treatment in patients with HPA, which could be useful in improving follow-up
strategies and clinical outcome. TRIAL REGISTRATION: Research Ethics Committee of
Santiago-Lugo 2015/393. Registered 22 September 2015, retrospectively registered.
PMID- 27612881
TI - Study on Neurological Consequence of Eclampsia.
AB - The present study was carried out in the Department of Obstetrics and Gynecology
at Mymensingh Medical College Hospital, Mymensingh, Bangladesh for a period of
one year from 1st June 2009 to 30th June 2010 to see the Neurological Consequence
of Eclampsia. A total number of 37 patients were enrolled in this study. Among 37
patients majority are in the age group of 21-30 years which is 19(51.4%) cases
followed by less than or equal to 20 years and more than 30 years which are
13(35.1%) cases and 5(13.5%) cases respectively. Knee jerk is present in
28(75.7%) cases and absent in 8(21.6%) cases. The exaggerated knee jerk is
present in only in 1(2.7%) case. The rate of Glasgow coma scale is less than 5 in
21(56.8%) cases, 14(37.8%) cases in 5-10 and 2(5.4%) cases is in more than 10.
Focal sign is absent in 22(59.5%) cases and present in 15(40.5%) cases. Majority
of the patients is presented with absence of neck stiffness which is 35(94.6%)
cases and the rest 2(5.4%) cases are presented with neck stiffness. Flexor
planter response is found in 20(54.1%) cases which is the highest in number
followed by extensor which is 15(40.5%) cases. In only 2(5.4%) cases the planter
reflex is not elicitable. Presence of infarct is found in 15(40.5%) cases which
is the highest number. Cerebral edema and Presence of haemorrhage is found in
3(8.1%) cases in each. Leuko-encephalopathy is found in 2(5.4%) cases.
Encephalopathy and Both infarct & haemorrhage is found in 1(2.7%) case of each.
Normal CT scan findings of brain are found in 12(32.4%) cases.
PMID- 27612882
TI - Detection of Cervical Cancer through Visual Inspection of Cervix with Acetic Acid
(VIA) and Colposcopy at Mymensingh Medical College Hospital.
AB - Cervical cancer is the second most common cause of cancer related morbidity and
mortality in women with 50% mortality rate. It is preventable if cervical
cellular changes are detected and managed at early stage. This was a
retrospective study conducted at VIA center of outpatient department and
Colposcopy clinic at in-patient department of Mymensingh Medical College
Hospital, Bangladesh covering a period from September 2013 to November 2014.
Objective of this study was detection of cervical cancer and precancerous
condition amongst patients reported to VIA center and Colposcopy clinic. In
primary screening at VIA Center, total respondents were 3604, their mean age was
35.9 and highest were in the age group 31 to 40 years. At VIA center, 110(3.05%)
were found positive and highest were between 31 to 40 years. In Colposcopy
Clinic, out of 700 patients, 51.7% were CIN 1, 4.9% CIN 2, 1.4% CIN 3, invasive
carcinoma was 0.3% and unsatisfactory or inconclusive were 34.3%. Most of the
respondents were housewives and majority had poor monthly income. Amongst
respondents, 72.1% were from rural area and Colposcopic findings revealed in
62.5% abnormal cervical changes, 46.5% were from rural area. Mean age at marriage
or age at first coitus was found 16.25 years and 92.7% were in 11 to 20 years.
Maximum abnormal cervical findings including CIN were between the ages ranged
from 11 to 20 years of marriage age. In patients having 1 - 5 number of child
having abnormal (58%) cervical changes, 48% were CIN 1. Histopathology reports
found 19.6% CIN 1 (Total CIN 20.7%), cervical carcinoma 1.3%, inflammatory 7.0%
and 0.42% cases were reported normal. Amongst 438 histopathology advised cases,
230 respondent's reports with patients were not available. VIA followed by
Colposcopy has been a feasible, easy and reliable tools for screening cervical
cancer in Bangladesh.
PMID- 27612883
TI - Fasting Serum Glucose Level in Postmenopausal Bangladeshi Women.
AB - The study was done to find out the causes that changes the fasting serum glucose
level in postmenopausal women. This was descriptive type of cross sectional study
carried out over a period of one year from July 2014 to June 2015 in the
department of physiology, Mymensingh Medical College, Mymensingh. Women of
reproductive age (25-45 years) and clinically diagnosed 100 menopausal women (45
70 years) were included for this study. Convenience type of sampling technique
was used for selecting the study subjects. Measurement of fasting serum glucose
was done by GOD-PAP method. Data were expressed as mean+/-SD and statistical
significance of difference among the groups were calculated by unpaired student's
't' test. The mean+/-SD of serum glucose in menopausal women were significant at
1% level of probability than women of reproductive age. This study revealed that
postmenopausal women showed higher levels of fasting serum glucose level. Fasting
blood sugar level between the study & control group were 7.69+/-2.37 and 4.59+/
0.73 and the difference was statistically significant.
PMID- 27612884
TI - Management of Infective Corneal Ulcer: Epidemiology Needs To Be Evaluated As
Priority Basis.
AB - Because of known and unknown etiology, management of ocular devastating situation
like corneal ulcer is still a challenge for the Ophthalmologists. The cross
sectional study was designed for detection of predisposing factor and
identification of causal agent. To serve the above purpose, a cross sectional
study was performed among 140 patients of the corneal ulcer at Dr K Zaman BNSB
Eye Hospital, Mymensingh and Department of Microbiology and Hygiene, Bangladesh
Agricultural University, Mymensingh, Bangladesh. Detail history of patient was
taken and recorded in a pretest questionnaire sheet. Two pieces of sample were
collected from each corneal ulcer patient. One sample was examined in KOH wet
mount for fungus. Other sample was nourished into nutrient broth and for further
culture and identification. Bacterial corneal ulcer was higher among the patient
of age group >=46 years (61.9%) followed by 31-45 years (21.5%). P value is
0.261. Males were found predominant (58.5%). P value is 0.13. Agricultural
related work was identified as most risky occupation in 83.1% of the total
bacteria positive samples. P value is 0.01. Trauma was noted as most predominant
influencing factor (56.9%). P value is <0.05. Bacteria were identified in
65(46.4%) and fungus in 40(28.6%) samples. Pseudomonas species were predominant
(52.3%) followed by Staphylococcus species (26, 2%) and Streptococcus species
(21.5%). No mixed infection was identified. For easier and earlier diagnosis of
corneal ulcer, information about epidemiology is very essential. History should
be taken meticulously followed by the laboratory procedures.
PMID- 27612885
TI - Effects of Intensive versus Non-Intensive Physical Therapy on Children with
Cerebral Palsy.
AB - Cerebral Palsy (CP) is one of the most common causes of all childhood disorders.
There are tone, posture and movements difficulty due to non-progressive damage to
the immature brain in CP. The hallmark of CP is a disability in the development
of gross motor function (GMF). The influence of gross motor development on fine
motor development is more important in early developmental period, specially
under three years old and in children with CP. Various therapeutic interventions
have been used in the management of GMF development. Among them physical therapy
is the most common intervention in CP and is usually a component of mandated
programs. Physical therapy means physical stimulations in the form of various
therapeutic exercises, touch, massage, limbs and trunk movement, balancing and
coordination training, gait and ambulation training, cognitive stimulation as
well as speech, language and occupational therapy. Our study focused to see the
effect by short term intensive versus non-intensive physical therapy on children
GMF development by using gross motor function measure (GMFM) Score sheet, GMFM
88, version 1.0. Study provides the information that physical therapy
intervention is effective in GMF development and intensive interventions are more
effective in children with spastic CP than non-intensive one. Study also inform
that the more early treatment the more effective result.
PMID- 27612886
TI - Serum LDL (Low Density Lipoprotein) As a Risk Factor for Ischemic Stroke.
AB - Atherosclerosis is the main risk factor of ischaemic stroke. Dyslipidaemia is the
main cause of atherosclerosis. High levels of LDL, also called "bad" cholesterol,
seem to provoke stroke. This case control study was conducted in Mymensingh
Medical College Hospital during the period of January 2012 to December 2012. The
study was carried out to measure the level of serum LDL (Low Density Lipoprotein)
of ischaemic stroke patients admitted in Medicine wards of Mymensingh Medical
College Hospital and the result of this study was compared with the level of LDL
cholesterol in age matched controls. Sample size was 384 which had been selected
by inclusion and exclusion criteria. Out of 384 samples 192 were cases and 192
were controls. Mean age +/-SD was 57.0+/-10.85 years in cases and 57.43+/-10.64
years in controls. Elderly people are the most vulnerable group for developing
stroke. LDL cholesterol level was more than 130mg/dl was found 88.54% among cases
and 33.85% among controls, the difference was statistically significant (p<0.05).
Mean LDL level +/-SD were 145+/-13.59mg/dl in cases and 125.01+/-10.73mg/dl in
controls. Odds ratio of LDL cholesterol were 15.0979 and 95% confidence limits
were 8.8396 to 25.7869 among cases and controls. This study explored study
population with higher LDL cholesterol was over fifteen times more likely to
developed ischaemic stroke. Early detection of high LDL cholesterol in the way to
prevent ischaemic stroke and thereby reduced the morbidity and mortality of
ischaemic stroke.
PMID- 27612880
TI - Colonization of Enteroaggregative Escherichia coli and Shiga toxin-producing
Escherichia coli in chickens and humans in southern Vietnam.
AB - BACKGROUND: Enteroaggregative (EAEC) and Shiga-toxin producing Escherichia coli
(STEC) are a major cause of diarrhea worldwide. E. coli carrying both virulence
factors characteristic for EAEC and STEC and producing extended-spectrum beta
lactamase caused severe and protracted disease during an outbreak of E. coli
O104:H4 in Europe in 2011. We assessed the opportunities for E. coli carrying the
aggR and stx genes to emerge in 'backyard' farms in south-east Asia. RESULTS:
Faecal samples collected from 204 chicken farms; 204 farmers and 306 age- and
gender-matched individuals not exposed to poultry farming were plated on
MacConkey agar plates with and without antimicrobials being supplemented. Sweep
samples obtained from MacConkey agar plates without supplemented antimicrobials
were screened by multiplex PCR for the detection of the stx1, stx2 and aggR
genes. One chicken farm sample each (0.5 %) contained the stx1 and the aggR gene.
Eleven (2.4 %) human faecal samples contained the stx1 gene, 2 samples (0.4 %)
contained stx2 gene, and 31 (6.8 %) contained the aggR gene. From 46 PCR-positive
samples, 205 E. coli isolates were tested for the presence of stx1, stx2, aggR,
wzx O104 and fliC H4 genes. None of the isolates simultaneously contained the
four genetic markers associated with E. coli O104:H4 epidemic strain (aggR, stx2,
wzx O104 and fliC H4 ). Of 34 EAEC, 64.7 % were resistant to 3(rd)-generation
cephalosporins. CONCLUSION: These results indicate that in southern Vietnam, the
human population is a more likely reservoir of aggR and stx gene carrying E. coli
than the chicken population. However, conditions for transmission of isolates
and/or genes between human and animal reservoirs resulting in the emergence of
highly virulent E. coli strains are still favorable, given the nature
of'backyard' farms in Vietnam.
PMID- 27612887
TI - Variations of Weight of Prostate Gland in Different Age Groups of Bangladeshi
Cadaver.
AB - Now a days, benign prostatic hyperplasia and carcinoma of the prostate are the
most common disorders in men. A cross sectional descriptive study was conducted
in Department of Anatomy, Mymensingh Medical College, Mymensingh to find out the
difference in weight of the prostate gland of Bangladeshi people in relation to
age. The present study was performed on 67 postmortem human prostate gland
collected from the morgue in the Department of Forensic Medicine, Mymensingh
Medical College by non random purposive sampling technique. The specimens were
collected from Bangladeshi cadaver of age ranging from 10 to 80 years. All the
specimens were grouped into three categories - Group A (upto 18 years), Group B
(19 to 45 years) and Group C (above 45 years) according to age. Dissection was
performed according to standard autopsy techniques. The weight of the prostate
gland were measured and recorded. The mean weight of the prostate gland was
10.13gm in Group A, 17.27gm in Group B and 22.50gm in Group C. Variance analysis
shows that mean differences of weight of the prostate were highly significant
among all age groups. The weight of prostate gland was found to increase with
increased age. For statistical analysis, differences between age groups were
analyzed by using students unpaired 't' test. The present study will help to
increase the information pool on the weight of prostate gland of Bangladeshi
people.
PMID- 27612888
TI - Study on Glycaemic Status and Lipid Profile in Type 2 Diabetic Patients Attending
Mymensingh Medical College Hospital, Mymensingh.
AB - Recent increases in the incidence of diabetes in developing countries have been
associated with complications resulting in mortality and morbidity. A case
control study of 120 subjects attending out patient department of Mymensingh
Medical College, Mymensingh was done with an aim to evaluate alteration of serum
lipid profile and HbA1c in type 2 diabetic patients and compare with age matched
healthy control. Of the total cases, 60 were Type 2 diabetic patients and 60 were
apparently healthy persons recruited for the study. These patients and control
subjects were classified as male (50%) and female (50%). Fasting lipid profile
and HbA1c% were measured by following the standard laboratory methods. The study
subjects had relatively poor glycemic control. The mean HbA1c was 9.21+/-1.19% in
diabetes patient and 4.71+/-0.60% was in control. The mean fasting blood glucose
level was 10.18+/-1.56mmol/L in diabetes patient and 4.51+/-0.48mmol/L in
control. The mean total cholesterol, triacylglycerols, HDL-C & LDL-C were
211.93+/-11.83mg/dl, 156.90+/-7.96mg/dl, 35.20+/-3.17mg/dl & 133.20+/-3.99mg/dl
in diabetes patient accordingly and the mean total cholesterol, triacylglycerols,
HDL-C & LDL-C were 159.72+/-4.89mg/dl, 117.45+/-12.97mg/dl, 44.23+/-2.75mg/dl &
92.15+/-5.67mg/dl in control group accordingly. The study revealed that the most
common abnormality seen was decreased serum HDL-Cholesterol levels (91.67%).
Hypertriglyceridaemia present in 81.67% patients, 78.34% had high LDL-Cholesterol
and 73.34% had hypercholesteromia. Diabetic males had significantly higher levels
of total cholesterol and LDL-Cholesterol compared to diabetic females and
diabetic females had significantly lower levels of HDL-Cholesterol compared to
diabetic males. It was concluded from the results of this study that, diabetic
patients are more prone to develop dyslipidaemia. Thus early diagnosis of
dyslipidemia and good glycaemic control can be used as a preventive measure for
the development of cardiovascular disease (CVD) in type 2 diabetics.
PMID- 27612889
TI - Clinical Profile and Biochemical Abnormalities of Neonatal Seizure at NICU of a
Tertiary Care Hospital.
AB - Seizures are most common neurological emergency in the neonatal period and
present as a diagnostic and therapeutic challenge to clinicians worldwide. This
prospective observational study was conducted in the Neonatal Intensive Care Unit
of Mymensingh Medical College Hospital from January 2015 to March 2015. Total 318
patients were enrolled in the study who presented with convulsion. Most of the
patients were term (72.95%) and birth weight was normal (77.3%). Around 75%
patients were delivered at home. Most common causes of convulsion were Perinatal
Asphyxia (78%) followed by Septicemia, Hypoglycemia and Meningitis in order of
frequency. Commonest type of seizure was subtle seizure (45.5%). Most of the
patients recovered completely (73%) and 8.4% patients died due to complications.
PMID- 27612891
TI - Apolipoprotein B versus Non- High Density Lipoprotein Cholesterol as a
Discriminating Factor for Acute Coronary Syndrome in Young People.
AB - This study aimed to compare Apolipoprotein B(Apo B) with non-HDL-C as a predictor
and discriminating factor of acute coronary syndrome (ACS). This is a case
control study among 50 cases of first attack of ACS among 18-45 years of age of
both sex, admitted in coronary care unit of Mymensingh Medical College Hospital,
Bangladesh from June 2009 to May 2010. Data was recently reanalyzed. Apo B is
more sensitive than non-HDL C (84% vs. 62%) as well with more negative predictive
value (NPV) (76.5% vs. 62.7%) but with similar positive predictive value (PPV)
(63%). Specificity was more for non HDL C than Apo B (64% vs. 52%). Highest
specificity and PPV observed for HDL- C, 88% and 71.4% respectively but with low
sensitivity (30%). In this study diagnostic value of LDL-C, TC and TG was low.
Apo B was a more discriminating factor as well predictor for ACS cases than non
HDL-C (OR: 5.678, 95% CI 2.227 - 14.528, P=0.001) vs. (OR: 2.901, 95% CI 1.288 -
6.534, P=0.01). Area under the Receiver Operating Characteristic (ROC) curve was
greater for Apo B than non-HDL-C (0.680 vs. 0.630). Though ApoB and non-HDL-C
theoretically often equally reflects the atherogenic burden, Apo B was a more
discriminating factor for ACS cases than non-HDL-C.
PMID- 27612890
TI - Antimicrobial Susceptibility Pattern of Methicillin-Resistance Staphylococcus
aureus from Different Tertiary Care Hospitals Including Mymensingh Medical
College Hospital.
AB - The aim of this study was to detect antimicrobial susceptibilities and the
presence of drug resistance genes of MRSA from tertiary care hospitals. This
study was carried out in the Department of Microbiology, Mymensingh Medical
College during the period from Jan, 2015 to Dec, 2015. Clinical samples,
including wound swab, pus, exudates from diabetic ulcer and burn ulcer, aural
swab, blood and urine were collected. Standard microbiological procedure &
biochemical tests were carried out to detect S. aureus. Oxacillin disk diffusion
test was done by Kirby-Bauer disk diffusion method. Total 69 isolates of S.
aureus were selected for the study. The isolates were collected from three
different tertiary care hospitals, of which 33, 27 and 9 were from Mymensingh
Medical College Hospital (MMCH), BIRDEM hospital and Sir Salimullah Medical
College Hospital (SSMCH) respectively. Among the 69 isolates, 17(24.6%) and
52(75.3%) were distinguished as MRSA and MSSA respectively by ODDM (Oxacillin
disk diffusion method). In contrast, detection of presence and absence of mecA
gene by PCR identified 20 (28.9%) and 49 (71.01%) isolates as MRSA and MSSA
respectively. All of the S. aureus (MRSA and MSSA) isolates were sensitive to
vancomycin and gentamicin. All MRSA isolates (100%) showed resistance to
Penicillin and Oxacillin. Among the MRSA isolates about 88.2% were resistance to
Ceftazidime, 64.7% were resistance to Erythromycin and Ciprofloxacin, 11.7% were
resistance to Tetracycline. Among the MSSA isolates about 94.2% were resistance
to Penicillin and 9.6% resistance to Ciprofloxacin. The MSSA were less resistance
for non-beta lactam drugs than MRSA. Regarding drug resistance genes, the blaZ
genes were present in 47 out of 49(95.8%) MSSA and in 18 out of 18 (100%) MRSA.
The erythromycin resistance gene ermB was found in 8.69% isolates, of which
highest 20% in MRSA and 4.08% in MSSA. The ermA was not found in any isolates.
Among tetracycline resistance genes, tetK were detected in 10.1% and tetL were
found in 2.8% of MRSA. The highest tetK genes were found in 20% of MRSA and in
6.1% of MSSA. Regarding, the gentamicin drug resistance, the aac(6')-Iaph(2'')-Ia
gene was not found in any isolates. The relatively high proportion of MRSA and
the associated antibiotic resistance seen in this study emphasizes the need for
country based surveillance to characterize and monitor MRSA and to develop
strategies that will improve MRSA treatment and control.
PMID- 27612892
TI - Early Outcome of Primary Repair in Colonic Injury.
AB - The management of the colon injury remains controversial in spite of a number of
divergent reports during the past decade. Previously surgeons were reluctant to
do primary anastomosis but now-a-days they are doing primary repair with good
results. The present study is designed to see the early outcomes of primary
repair in colonic injury. This prospective observational study performed at Dhaka
Medical College Hospital, Dhaka, Bangladesh from January 2013 to June 2013 with
allocation of 50 patients with colonic injury who underwent laparotomy with
primary repair of that injury in the department of Casualty Surgery. A primary
repair was performed after freshening the edges or by resection and primary
anastomosis with 3.0 round-body Vicryl by single layer extra mucosal interrupted
suture. Data processed using software SPSS version 16.0. For all analytical
results a p value <0.05 was considered significant. In this study the commonest
site of injury were transvers colon and sigmoid colon 38.0% in each. Out of 50
respondents, 5(10.0%) developed burst abdomen, 1(2.0%) developed entero-cutaneous
fistula with none had paralytic ileus or septicaemia or pelvic collection. No
mortality observed. This study showed that the increasing in colon injury scale
(CIS) score culminate into increasing rate of postoperative complication & post
operative complications were more at left colon (24%). On basis of our findings,
we recommend the primary repair is a safe and effective surgical technique for
addressing the large gut injury. Unnecessary proximal diversions should be
avoided. According to our experience, we believe that the policy of primary
repair of colon injuries can be applied more liberally in majority of patients
with high success rate.
PMID- 27612893
TI - B-type Natriuretic Peptide Assay in Differentiating Congestive Heart Failure from
Lung Disease in Patients Presenting with Dyspnea.
AB - This cross-sectional analytical study was conducted in Cardiology & Medicine
Department of Mymensingh Medical College Hospital. After fulfilling the exclusion
& inclusion criteria, B-type natriuretic peptide concentrations were measured in
a convenience sample of 100 predominantly male (94%) dyspnic patients who got
admitted in Cardiology & Medicine Department of Mymensingh Medical College &
Hospital from November 2013 to October 2014. The diagnosis of Congestive Heart
Failure (CHF) was based on generally accepted Framingham criteria with
corroborative information including hospital course (response to diuretics,
vasodilators, inotropes or hemodynamic monitoring) and results of further cardiac
testing, including echocardiography. Patients with right heart failure from cor
pulmonale were classified as having CHF. Pulmonary disease was confirmed by using
the following diagnostic tools: i) A chest X-ray without signs of heart
enlargement or pulmonary venous hypertension or a chest X-ray with signs of
chronic obstructive lung disease, ii) Normal heart function as seen by
echocardiography, iii) Abnormal pulmonary function tests or follow-up results and
iv) A positive response to treatment with steroids, nebulizers or antibiotics in
hospital. Patients with CHF (n=50) had mean BNP level 1146.72pg/ml (range 103 to
5000pg/ml), which is significantly higher than the group of patients with a final
diagnosis of pulmonary disease (n=50) whose BNP was 34pg/ml (range 10 to 90pg/ml)
(p<0.05). In conclusion, it was found that B-type natriuretic peptide is an
important biomarker for differentiating congestive heart failure from lung
disease in patients presenting with dyspnea.
PMID- 27612894
TI - In Vitro Determination of Minimum Inhibitory Concentration of Aqueous Garlic
Extract and Imipenem against Staphylococcus aureus and Escherichia coli.
AB - An interventional study was performed to determine and compare the MICs of
aqueous garlic extract (AGE) and Imipenem against standard strains of
Staphylococcus aureus ATCC 25923 & Eschericha coli ATCC 25922. The study was
conducted in Department of Pharmacology and Therapeutics in collaboration with
Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh
from July 2014 to January 2015. The MIC of AGE and antibiotic Imipenem were
determined with the help of broth dilution method. The MIC of AGE was determined
as 400MUg/ml and 700MUg/ml against Staphylococcus aureus, and Escherichia coli
respectively and the MIC of Imipenem was 1MUg/ml against Staphylococus aureus and
1.5MUg/ml against Escherichia coli. The MICs of Imipenem was much lower in
comparison to MICs of AGE for the test organisms. The subculture study showed the
same results with that of the primary isolates. From the study it was clearly
observed that AGE have anti bacterial effect but is not potent like antibiotic
Imipenem. In this regard active ingredient present in garlic needs to be
separated & purified for further study.
PMID- 27612895
TI - Evaluation of Iron Store by Serum Ferritin in Healthy Blood Donors of Bangladesh.
AB - Iron stores in the body exist primarily in the form of ferritin. Small amounts of
ferritin secreted into the plasma and plasma ferritin is positively correlated
with the size of the total body iron stores. The present study conducted to
determine the iron status using the serum ferritin level among healthy
Bangladeshi blood donors. The present cross sectional study was conducted in the
Department of Transfusion Medicine, Dhaka Medical College, Dhaka, Bangladesh from
July 2011 to June 2012. Blood donor signed informed consent and has satisfactory
pre-donation health assessment and satisfactory post-donation blood test results
were included in the study. Full blood counts were performed within 4 hours of
collection using an automated haematology analyzer. Serum ferritin was measured
using a validated enzyme immunoassay. Data were analyzed using SPSS version 16
(SPPS Incorporation, Chicago, IL, USA). P value <0.05 was considered as
statistically significant. Total 100 blood donors were included in the study,
among them 88 were male and 12 were female. Mean+/-SD of the age of the
respondents was 26.8+/-5.9 years with a range of 19 to 45 years. Mean+/-SD of
heamoglobin level (gm/dl) and total count of Red Blood Cell (million/cmm) were
14.1+/-1.4 and 5.1+/-0.4 respectively. Mean+/-SD of serum ferritin level (ng/ml)
was 96.4+/-69.0ng/ml with a range of 4.1ng/ml to 298.7ng/ml. Among the
respondents 9.0% had depleted iron store, 7.0 reduced iron store and 84.0% had
normal iron store. Among the respondents 5.0% had iron deficiency anaemia in term
of serum ferritin level. Statistically significant difference of serum ferritin
level observed between male and female and donors with and without history of
previous blood donation. Among the healthy blood donors of Bangladesh abnormal
serum ferritin is highly prevalent among blood donors specially among female.
Monitoring of iron stores by serum ferritin seems justified in order to identify
those with depleted iron stores who will benefit from iron supplementation.
PMID- 27612896
TI - Aetiology and Outcome of Acute Liver Failure in Children: Experience at a
Tertiary Care Hospital of Bangladesh.
AB - Acute liver failure (ALF) is a rapidly progressive, potentially fatal syndrome
resulting from rapid death or injury to a large proportion of hepatocytes, caused
by a variety of insult, leaving insufficient hepatic paranchymal mass to sustain
liver function. The aetiology of ALF varies according to the age of patient and
development of the country. The outcome of ALF also varies according to
aetiology: survival is better in paracetamol poisoning whereas it is poor in
metabolic diseases. The present study was undertaken to observe the underlying
aetiology and outcome of ALF in children under 18 years of age admitted at the
department of Paediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib
Medical University, Dhaka, Bangladesh. It was a retrospective review of medical
records from November 2011 through October 2014. During this period a total of 35
patients were diagnosed to have ALF. Aetiology was established in 25(71.4%)
cases, whereas in 10(28.6%) cases, no identifiable cause was found. Viral
hepatitis was the underlying cause in 12(34.3%) cases. After treatment 15(43%)
ALF patients survived, 8(23%) left hospital with risk bond (DORB), and 12(34%)
patients died. The study showed that among the 12 death patients, 5(41.7%) had
viral hepatitis, 3(25%) Wilson's disease, and in 4(33.3%) no cause could be
identified. Viral hepatitis and Wilson disease were found to be two common causes
of ALF in this study. Future studies with larger sample size are required to know
the actual causes of acute liver failure in Bangladeshi children.
PMID- 27612897
TI - Close Intramedullary Interlocking Nailing Versus Locking Compression Plating In
the Treatment of Closed Fracture Shaft of the Tibia.
AB - Fracture of tibial shaft is the commonest site of long bone fractures due to its
superficial location involving young or middle-age people. Proper management is
an important issue regarding the future effective movements. In this study
patients were grouped in closed Intra medullary interlocking nailing and locking
compression plating. Post-operative follow up at 2 weeks, 6 weeks, 12 weeks and 3
months thereafter up to 6 months were done. Each of the patients was evaluated
clinically and radiologically by tucker criteria of Tuker et al. Patients were
assessed for pain on full weight bearing and kneeling, shortening and range of
motion of knee and ankle joints. Radiological assessment for union of fracture,
alignment of fracture and angulations and position of nail and screws and
infection were observed during follow up. A total number of 32 patients were
selected but only 27 patients were available for follow up for a period of 6
months. They were grouped into Group A, consisting of 15 patients who took the
treatment in the form of closed intramedullary interlocking nailing and Group B,
consisting of 12 patients those underwent ORIF with locking compression plating.
In both of the groups Motor Vehicle Accident was the main mechanism of trauma.
Fracture involving the middle 3rd of the tibia is common in both the groups.
During post-operative follow up, four patients in Group A complained anterior
knee pain, one patient in Group B had superficial infection, most of the patients
had no restriction of movement in the ankle and knee joints and a single patient
in Group B showed 1.5cm shortening of the lower limb. Period of hospital stay and
fracture union time were less in Group A, which was statistically significant.
Both groups showed excellent result with minimum complications. So this study
permits to conclude that close IM interlocking nailing and open reduction and
internal fixation by locking compression plating is equally effective for the
management of close fracture shaft of the tibia.
PMID- 27612898
TI - Correlation between Clinical and Arthroscopic Findings in Meniscal Tear of Knee.
AB - The meniscus is the most commonly injured structure in the knee joint. Carefully
performed clinical examination can give better diagnosis of meniscal tear. The
aim of this study was to find out the correlation between clinical and
arthroscopic findings in meniscal tear of knee. This cross sectional
observational study was conducted in the Department of Orthopaedic Surgery,
BSMMU, Dhaka from July 2012 to June 2014. Thirty patients of meniscal tear were
selected as per inclusion and exclusion criteria. After proper evaluation and
clinical examination of these patient arthroscopic examinations was done under
spinal anesthesia. A total number of 30 patients were recruited in this study.
Twenty seven (90%) patients were male and only 3(10%) were female. Mean+/-SD of
age was 26.00+/-5.55 and range was 17-34 years. Out of 30 patients 19(63.3%) had
right knee affected and the rest 11(36.7%) had left knee affected. It was found
from clinical diagnosis that most of the patients had MM injury (73.4%) and LM
injury was in 26.6% patients. From arthroscopic diagnosis we found most of the
patients had multiple types of injury (40.0%) followed by 26.7% patents had
isolated MM injury, 16.6% patients had isolated LM injury, 10.0% patients had
other injuries like ACL, PCL or MCL and rest 6.7% patients had no injury at all.
Sensitivity, specificity, PPV, NPV and accuracy of clinical diagnosis in
diagnosis of MM injury were 94.4%, 58.3%, 77.3%, 87.5% and 80.0% respectively.
Sensitivity, specificity, PPV, NPV and accuracy of clinical diagnosis in
diagnosis of LM injury were 85.7%, 91.3%, 75.0%, 95.5% and 90.0% respectively.
Clinical evaluation may diagnose meniscal tear accurately.
PMID- 27612899
TI - Iron Polymaltose Complex in the Treatment of Iron Deficiency Anemia in Pregnancy.
AB - Iron deficiency anaemia is a major public health problem in pregnancy. About 58%
of pregnant women in developed countries are anaemic mainly due to iron
deficiency resulting a serious negative consequences on children, mothers and
eventually on the nation. This quasi-experimental multi centered study (Before
after study) was done to evaluate the efficacy and tolerability of Iron
Polymaltose Complex (IPC) in the treatment of iron deficiency anaemia and it was
performed at the OPD of Bangladesh Medical College and two other clinics of Dhaka
city from August 2011 to September 2013. A total of 80 (eighty) subjects were
selected by purposive sampling as per inclusion and exclusion criteria. They were
treated by Iron Polymaltose-IPC [47mg elemental iron + Folic Acid 0.5mg + Zinc
22.5mg - Once daily orally for 12 weeks]. At the beginning and after 12 weeks of
intervention by Iron Polymaltose Complex (IPC) Hb%, Packed Cell Volume (PCV),
Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Serum iron, and
Serum ferritin were measured. Data were analyzed by SPSS version 13.0. Paired and
unpaired 't' test was used to analyze differences within groups and between
groups. Chi-square test was done to analyze primary efficacy parameters and
adverse drug reactions (ADR). Most of the respondents were within the age group
of 18-23 and 30-35 years (32.6% each). Significant differences were found by
treatment with IPC for 12 weeks in Hb%, PCV, MCV, MCH, Serum iron, and Serum
ferritin level. In iron deficiency anaemia during pregnancy IPC may be used as a
safe and cost-effective therapeutic management.
PMID- 27612900
TI - Surgical Outcome of Intradural Spinal Tumors.
AB - Results of 63 surgically treated intradural spinal tumors between the period of
October 2003 and December 2014 at Bangabandhu Sheikh Mujib Medical University
(BSMMU) and in our private settings, Dhaka, were analyzed retrospectively. There
were 33 males, 30 females with an average age of 52.4 years (13-70 years) and
followed up for at least a year. The preoperative symptom with duration, tumors
location and intradural space occupancy and the histopathological diagnosis were
analyzed. Pain was evaluated by the visual analogue scale (VAS) and the
neurologic function was assessed by Nurick's grade. The tumors were located as,
thoracic (n=32, 50.79%), lumbar (n=16, 25.39%), cervical (n=05, 07.93%), and
junctional (n=10, 15.87%, CervicoThoracic-01, Thoracolumbar-09). The
histopathological diagnosis included schwannoma (n=30, 47.7%), meningiomas (n=14,
22.3%), neurofibroma, arachnoid cyst and myxopapillary ependymoma (n=03, 04.76%)
each and paraganglioma (n=01, 01.59%). Among the intramedullary tumors,
ependymoma (n=03, 04.76%), astrocytoma and epidermoid cyst (n=02, 03.17%),
haemangioblastoma, paraganglioma and cavernous haemangioma (n=01, 01.59%) each.
The VAS score was reduced in all cases from 8.0+/-1.2 to 1.2+/-0.8 (p<0.003) and
the Nurick's grade was improved in all cases from 3.0+/-1.3 to 1.0+/-0.0
(p<0.005). The preoperative neurological deficit improved within 8 postoperative
weeks in most cases and within 1 postoperative year in all cases. Complications
included cerebrospinal fluid leakage, parasthesia and further neurological
deterioration (Astrocytoma) (n=02, 03.17%) and dependant bedsore and recurrence
(Ependymoma) (n=01, 01.59%). Aggressive surgical excision potentially minimizes
neurologic morbidity and improved outcome except intramedullary tumors where
initial treatment consists of maximum safe surgical resection or biopsy.
PMID- 27612901
TI - Use of Anticoagulant Warfarin in Patients Presenting With Atrial Fibrillation in
a Tertiary Level Hospital.
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia in the World,
occurring in approximately 0.4% of the general population. The purpose of the
present study was to see the trend of use of warfarin in hospital admitted
patients with atrial fibrillation. It was conducted in the department of
cardiology, University Cardiac Centre, Bangabandhu Sheikh Mujib Medical
University, Dhaka, Bangladesh from January 2008 to January 2009. A total of 150
patients with atrial fibrillation were enrolled in this study. Out of them, male
were 60(40%) and female 90(60%); age range 22-79 years. Most common presenting
symptoms were palpitation (80%) & dyspnoea (70%). Chronic rheumatic heart disease
(Mitral stenosis) (33%) was found in most cases followed by IHD (22%),
hypertension (21%). According to CHADS2 score, most of the patients belonged to
moderate risk group (47%) and 32% in low risk group. Anticoagulation with
warfarin was used in 40% cases of valvular AF & 25% patients with non valvular
AF. Among non valvular AF, it was prescribed for 38% in high risk group, 34% in
moderate risk & 3% in low risk group. The study states that warfarin is underused
in both valvular & non valvular AF.
PMID- 27612902
TI - Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV in Overseas Job
Seekers of Bangladesh with the Possible Routes of Transmission.
AB - Hepatitis and AIDS are major public health problem globally. The aim of this
study was to determine the sero-prevalence of hepatitis B, C virus and HIV
infection among Bangladeshi overseas job seekers. This cross sectional study was
carried out in the Department of Microbiology of Dhaka Medical College, Dhaka,
Bangladesh from February 2013 to August 2013. A total of 2254 adult (18-45 years)
male job seekers to Malaysia attending for health check up were enrolled. HBsAg,
Anti-HCV, Anti-HIV were detected from venous blood by ELISA method using
commercial kits. From the positive people, further history and information were
collected by predesigned questionnaire. Prevalence of HBV was 2.35%, HCV was
0.13% and none was found positive for HIV. Prevalence of hepatitis was higher in
the age group of 21-30 year and infection was more prevalent in married group. No
significant relationship was found between hepatitis infection and religion,
localities, profession. Only a few cases had history of possible major known
route of transmission of virus. But most of them had history of taking injection
or sharing blades in barber shop and history of circumcision. About 96%
population had no history of hepatitis B vaccination. None was co-infected with
HBV and HCV. Prevalence of hepatitis B virus infection in adult population
appears to be on decline and hepatitis C and HIV infection is still low in
Bangladesh. In majority of the positive person, routes of transmission of viruses
were not well established.
PMID- 27612903
TI - Outcome of Extended Thymectomy in Myasthenia Crisis Patient.
AB - Myasthenic crisis is a life-threatening condition. We studied the demographic,
frequency, causes and clinical presentation of isolated Myasthenic crisis, steps
of treatment and to review our experience of extended thymectomy on patients with
at least one episode myasthenic crisis. A prospective and retrospective study was
conducted on patients with at least one episode of myasthenic crisis, from March
2010 to September 2014, at the Department of Cardiac Surgery, BSMMU, Dhaka,
Bangladesh who were referred for thymectomy. Eighteen patients (13.6% of the
total 132 patients with myasthenia gravis were admitted with single to multiple
episodes of myasthenic crisis, median crisis was 2.5 episodes. Mean age of the
patient was 35.5 (18-72) years with male predominance. All eighteen patients had
undergone extended thymectomy after completion of 5 cycle plasmapheresis, of
which 2 had experienced postoperative respiratory crisis, required invasive
ventilator support for median 14 days. One patient required invasive ventilator
support after third post operative day. Six patients had thymoma and 12 had
thymic hyperplasia. Three patients needed Intravenous immunoglobin. Nine patients
needed post operative anti acetylcholinesterase inhibitor after median 2.5 post
days. Post thymectomy remission and decreases the frequency of myasthenic crisis
was seen in follow up and post operative medication requirement reduced
significantly as compared to the preoperative requirement. This report highlights
that the patients who had extended thymectomy after episodes of myasthenia crisis
are benefitted even in the histhopathology report does not confirmed thymoma.
After thymectomy, there was remission of myasthenic crisis. Patients with
myasthenic crisis should have judicious drug adjustments under supervision and
should be treated aggressively during impending myasthenic crisis. With modern
management of myasthenia gravis, early surgery with myasthenic crisis is safe
with good long-term outcomes.
PMID- 27612904
TI - Outcome Analysis of Fernandez Osteotomy in Malunited Extra-Articular Fractures of
Distal Radius.
AB - Deformity of wrist is very common after mal union of extra articular fractures
over distal end of Radius. It causes limitation of movements too in different
directions with or without pain. Deformity may be treated by different types of
corrective osteotomy. We treated cases of this type of malunion with Fernandez
osteotomy. This study is to observe the amount of correction and recovery of
functional status in patients with malunited distal radius fractures treated with
Fernandez osteotomy. This is a prospective study. We treated 10 cases of
malunited radius with Fernandez osteotomy from February 2013 to October 2014 in
the Departments of Orthopaedics, Medical College and Hospital, Kolkata, India.
There were six males and four females with mean age of thirty years (with range
from twenty to forty years. Indications for surgical intervention include pain
and functional deficit severe enough to interfere significantly with daily
activities. Radius is exposed through distal dorsal radial incision and radial
osteotomy done two and half centimetre proximal to the wrist joint and after
achieving correction; gap is filled with iliac bone graft and fixed with
contoured distal radius T-plate. Follow up was for an average one year and three
months. Results were excellent in one, satisfactory in four cases, good in four
cases and bad in one case. Fernandez osteotomy is valuable option for correction
of malunited distal radius fracture especially in young demanding patients.
PMID- 27612905
TI - Evaluation of Hepatitis B Vaccination among Lichen Planus Patients.
AB - Lichen planus (LP) is an idiopathic chronic inflammatory mucocutaneous disease.
Many reports in the literature have described hepatitis B vaccine as a
predisposing factor for LP. This study was performed to determine the rate of
previous vaccination against hepatitis B in LP patients. This was a cross
sectional study on LP patients. Diagnosis of LP was confirmed by histological
examination. Data were gathered by dermatology residents based on a checklist
designed to guide their interview. Blood samples were tested for HBsAB titer,
HBsAg, HCV Ab and liver function tests. One hundred & twenty four (124) patients
entered the study. Females were 2.72 times more affected. The mean age of
patients was 45.63 years (age range; 18-88). Forty-four (35.5%) patients had been
vaccinated against hepatitis B. Lichen planus during the first six months of
vaccination occurred in only one patient. Our findings bring into question the
causative role of HBV vaccine in LP incidence in our population.
PMID- 27612906
TI - Removal of Unusually Large Torpedo Sialolith from Wharton's Duct under Local
Analgesia: A Case Report.
AB - Submandibular salivary gland system is commonly affected with sialolith
(calculus) and victim suffers painful acute symptoms. Sialoliths usually are of 1
15mm in size. Although rarely giant sialoliths are seen, a giant torpedo
sialolith of about 41mm * 9mm within the submandibular salivary duct is reported
which was removed intraorally under local analgesia. Post-operatively, within six
weeks salivation through duct was evidenced showing the process of re
establishment of salivary function.
PMID- 27612907
TI - A Giant Intra Abdominal Mass Mimicking Renal Cell Carcinoma: A Rare Presentation
of Renal Angiomyolipoma.
AB - Angiomyolipoma (AML) is a benign tumor commonly found in kidney than extra renal
sites. Most of the small renal angiomyolipomas are diagnosed incidentally on
ultrasound and other imaging studies. Some renal AMLs present clinically when
become very big, giant renal angiomyolipoma. Although almost all cases are
benign, a relatively rare variant of epitheloid angiomyolipoma has got malignant
potential and can even metastasize. Ultrasonography, CT and MRI scan are usually
used for diagnosis of angiomyolipoma with high level of accuracy; even though
some lesions may be confused as renal cell carcinoma on imaging studies. Here, a
48 year old man presented with a large intra-abdominal mass preoperatively
diagnosed as a case of right renal cell carcinoma and radical nephrectomy was
performed. Histopathology revealed epitheloid angiomyolipoma (EAML).
PMID- 27612908
TI - Spontaneous Resolution of Delayed Post-operative Extradural and Epicranial
Pneumatocele.
AB - Extradural and epicranial pneumatocele is a rare condition. It may complicate
with CSF rhinorrhoea and meningitis which can have a fatal outcome. We present a
case of delayed post-operative extradural and epicranial pneumatocele in the
frontal region following primary repair of the anterior skull base for a
traumatic compound craniofacial injury with CSF leakage. There was no evidence of
meningitis or raised ICP. As the patient was neurologically stable; he was
managed conservatively and had a spontaneous resolution of the pneumatocele.
PMID- 27612909
TI - Ilizarov Method: A Limb Salvage Device in a Child.
AB - Ilizarov method is the best weapon for the treatment of the limb length
discrepancy, especially in traumatic or congenital shortening of long bones. Post
burn bony defect can be corrected by osteosynthesis. Here we treated a 7 years
old boy, suffering from 33% electric burn affecting face, trunk, left upper limb
& both lower limbs with loss of soft tissue of medial side of right leg along
with dead and exposed of some segment (about 14cm) of Left tibia . Initially the
patient was managed by plastic surgeons in the form of surgical toileting, wound
debridement and wound coverage by split thickness skin graft. After about 6
weeks, we applied Ilizarov fixator on the affected limb and maintained it for 7
days to increase vascularity. As there was minimum bone in the proximal part, we
did corticotomy at the distal end. After 7 days further, we started distal to
proximal bone transport at a rate of 1mm per day. Staged excision of about 2.5 to
3cm dead bone was done, after transporting the same length of bone each time. In
5 such sittings, a total of 14cm bone was excised. Thus the burned portion was
replaced by new bone; bony union was achieved after applying compression. Now the
patient is able to walk individually, without any difficulty. So, we found that,
Ilizarov method is a good option for the management of post burn bone loss. To
our knowledge, such an application of the Ilizarov external fixation device in
post burn bone loss has yet to be reported.
PMID- 27612910
TI - An Unusual Case of Suicide Attempt Using Intravenous Injection of Kerosene.
AB - Kerosene belongs to the hydrocarbon group of compounds, used as a fuel for lamps,
as well as heating and cooking in developing countries. Accidental kerosene
poisoning and intoxication usually occur by inhalation or by occupational
percutaneous absorption. Adults usually ingest kerosene for the purpose of self
harm, and children may ingest accidentally. Suicidal attempt using intravenous
kerosene is an extra ordinary and very rare occurrence. A very few data are
available regarding effects of intravenous administration of kerosene and its
management.
PMID- 27612911
TI - Tuberculosis is a Mimicker of JIA: A Rare Case Report.
AB - Cystic tuberculosis of the bone is a rare form of tuberculosis (TB). The
condition presents like Juvenile idiopathic arthritis (JIA) of children. In
children, the lesions symmetrically involve the peripheral skeleton, which are
less sclerotic than adults. A case report is presented here where the patient
presented with i) the extensive involvement of bones with cystic lesion, ii) Hand
& feet involvement with multiple bony exostosis iii) Synovial swelling of
multiple joints and 4) fever for 6 months. Swelling of the joints was
disproportionately greater than pain. For the last 6 month patient developed low
grade fever with evening rise of temperature & dry cough. There was associated
anorexia & significant weight loss. Patient was moderately anaemic & there was
cervical lymphadenopathy on both sides. The chest examination revealed features
suggestive of consolidation in the right lung. Regarding MSK findings there was
swelling of both knee & right wrist with G-II tenderness, sublaxation of both
anterior and posterior cruciate ligament with mild effusion. Bony exostosis at
the base of left index finger & at the base of right middle finger was found.
Investigation shows low Hb, very high ESR, positive tuberculin test. X-ray Chest
suggestive of consolidation, FNA of right cervical lymph node consistent with
tuberculosis. X-ray Pelvis has shown expansile mixed sclerotic radiolucent areas
with interval septation involving upper part of both femoral shafts. MRI findings
of right knee joint were suggestive of tuberculous osteomyelitis. At this stage
the patient was put on Anti-TB chemotherapy. After 2 month and 4 month of follow
up with Anti-TB drug both MSK & lung condition was improved significantly.
Ultimately the patient was diagnosed as cystic tuberculosis of bone & continued
Anti-TB drugs.
PMID- 27612912
TI - Surgical Management of Desmoid Tumor of the Female Pelvis: A Case Report.
AB - A 25 years married women having one child delivered vaginaly presented in the
department of Obs & Gynae, Bangabandhu Sheikh Mujib Medical University,
Bangladesh on April 2013 with pelvic pain and discomfort. No history of previous
pelvic trauma was present. Patient examination showed a isolated mass in the
right lower abdomen, right adnexa, extending to the pelvic wall upto lower end of
ureter. Tumor markers were within normal limit. Intravenous pyelogram (IVP)
showed mild right hydroureter and hydronephrosis with obstruction at the lower
end of ureter. She was diagnosed as a case of adnexal mass with mild hydroureter
& mild hydronephrosis and it was decided to operate on the patient. The surgical
approach was transabdominal. On laparotomy a pseudocystic lesion 12*10cm in size
was found over the right paracolic gutter and extending down into the pelvis
involving the right parametrium. No abnormality was found in the uterus or tubes.
The histological examination revealed a desmoid tumor of the pelvis. The
patient's recovery was uneventful.
PMID- 27612913
TI - Ruptured Aneurysm of Sinus of Valsalva: A Case Report.
AB - We have presented a case of ruptured aneurysm of sinus of valsalva, in a female
of 24 years old, with the symptoms and signs of right heart failure. Diagnosis
made by echocardiography. For further evaluation, cardiac catheterization was
done. After improvement of her general condition, she was undergone operation.
Per-operative findings were bicuspid aortic valve having no calcification. A
fistulous tract having windsock appearance found in between fused RCC & NCC
extending into the RV cavity, which was opened inferior to the tricuspid valve.
Fistulous tract was excised and the opening in the root of the aorta was closed
with PTFE patch by 5/0 polypropylene and RV side was closed by direct suture.
Patient was symptomless after operation. Patient discharged on eighth
postoperative day in stable condition.
PMID- 27612914
TI - Migraine in Children: A Review.
AB - Recurrent headache is common in children. Among them migraine is the most common
disabling cause of primary headache. It causes serious disability in child's life
and family. It causes negative impact on their quality of life. Clinical
characteristic of migraine in children differ from adult. It may be shorter in
duration and bifrontal or bitemporal in location in contrast to adult which is
longer in duration and usually unilateral. It is less common before 3 years of
age. Males are more affected before puberty. But after puberty females are
predominantly affected. Intensity of pain is moderate to severe. There are some
triggering factors. Positive family history usually present. Disability can be
assessed by PedMIDAS scale in children and adolescents which is modified version
of MIDAS scale for adult. Diagnosis of migraine usually clinical but evaluation
should be done to exclude severe underlying secondary cause. Management consists
of pharmacological and non pharmacological approach. Parental education, life
style modification is the mainstay of management. Acute treatment consists of
Acetaminophen, NSAIDs and Triptans. Among Triptans, Sumatriptan nasal spray is
only found effective for children. Preventive therapy aims to decrease frequency
and severity of headache. Flunarizine, Propranolol, Amitryptylline,
Levetiracetam, Valproate, Topiramate are found effective in pediatric age group.
Pediatrician should evaluate the child to exclude secondary cause of headache
when indicated. They should have also proper knowledge and skills to manage a
child having migraine to improve their quality of life and academic achievement.
PMID- 27612916
TI - A Rare UGT2B7 Variant Creates a Novel N-Glycosylation Site at Codon 121 with
Impaired Enzyme Activity.
AB - The UDP glucuronosyltransferase (UGT) superfamily comprises glycoproteins that
reside in the endoplasmic reticulum membranes and that undergo post-translational
modifications (PTMs). UGT2B7 is of particular interest because of its action on a
wide variety of drugs. Most studies currently survey common variants and examine
only a small fraction of the genetic diversity; however, rare variants (frequency
<1%) might have a significant effect because they are predicted to greatly
outnumber common variants in the human genome. We discovered a rare single
nucleotide UGT2B7 variant of potential pharmacogenetic relevance that encodes a
nonconservative amino acid substitution at codon 121. This low-frequency
variation, found in two individuals of a population of 305 healthy volunteers,
leads to the translation of an asparagine instead of an aspartic acid (UGT2B7
p.D121N). This amino acid change was predicted to create a putative N
glycosylation motif NX(S/T) subsequently validated upon endoglycosidase H
treatment of microsomal fractions and inhibition of N-glycosylation of
endogenously produced UGT2B7 with tunicamycin in human embryonic kidney (HEK293)
cells. The presence of an additional N-linked glycan on the UGT2B7 enzyme, likely
affecting proper protein folding, resulted in a significant decrease of 49% and
40% in the formation of zidovudine and mycophenolic acid glucuronides,
respectively. A systematic survey of the Short Genetic Variations database
uncovered 32 rare, naturally occurring missense variations predicted to create or
disrupt N-glycosylation sequence motifs in the other UGT2B enzymes. Collectively,
these variants have the potential to increase the proportion of variance
explained in the UGT pathway resulting from changes in PTMs, such as N-linked
glycosylation with consequences on drug metabolism.
PMID- 27612915
TI - Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a
mouse model.
AB - BACKGROUND: Cancer pain, especially the one caused by metastasis in bones, is a
severe type of pain. Pain becomes chronic unless its causes and consequences are
resolved. With improvements in cancer detection and survival among patients, pain
has been considered as a great challenge because traditional therapies are
partially effective in terms of providing relief. Cancer pain mechanisms are more
poorly understood than neuropathic and inflammatory pain states. Chronic
inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl
cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the
analgesic effects of NB001 on cancer pain were evaluated. RESULTS: Pain was
induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the
intramedullary cavity of the femur of mice. The mice injected with sarcoma cells
for four weeks exhibited significant spontaneous pain behavior and mechanical
allodynia. The continuous systemic application of NB001 (30 mg/kg,
intraperitoneally, twice daily for three days) markedly decreased the number of
spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001
decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1
(831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the
frequency of presynaptic neurotransmitter release in the anterior cingulate
cortex of the mouse models. CONCLUSIONS: NB001 may serve as a novel analgesic to
treat bone cancer pain. Its analgesic effect is at least partially due to the
inhibition of AC1 in anterior cingulate cortex.
PMID- 27612917
TI - A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of
Multiple Brain Metastases.
AB - BACKGROUND: In this treatment planning study, we compare the plan quality and
delivery parameters for the treatment of multiple brain metastases using 2
monoisocentric techniques: the Multiple Metastases Element from Brainlab and the
RapidArc volumetric-modulated arc therapy from Varian Medical Systems. METHODS:
Eight patients who were treated in our institution for multiple metastases (3-7
lesions) were replanned with Multiple Metastases Element using noncoplanar
dynamic conformal arcs. The same patients were replanned with the RapidArc
technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed
using a single isocenter. Plan quality metrics (conformity index, homogeneity
index, gradient index, and R50%), monitor unit, and the planning time were
recorded. Comparison of the Multiple Metastases Element and RapidArc plans was
performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed
rank test. RESULTS: A paired Wilcoxon signed rank test between Multiple
Metastases Element and RapidArc showed comparable plan quality metrics and dose
to brain. Mean +/- standard deviation values of conformity index were 1.8 +/- 0.7
and 1.7 +/- 0.6, homogeneity index were 1.3 +/- 0.1 and 1.3 +/- 0.1, gradient
index were 5.0 +/- 1.8 and 5.1 +/- 1.9, and R50% were 4.9 +/- 1.8 and 5.0 +/- 1.9
for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose
was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans,
respectively. The mean value of monitor units in Multiple Metastases Element plan
was 7286 +/- 1065, which is significantly lower than the RapidArc monitor units
of 9966 +/- 1533 ( P < .05). CONCLUSION: For the planning of multiple brain
lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element
planning software produced equivalent conformity, homogeneity, dose falloff, and
brain V12 Gy but required significantly lower monitor units, when compared to
RapidArc plans.
PMID- 27612918
TI - Blood metal ion levels are not a useful test for adverse reactions to metal
debris: A systematic review and meta-analysis.
AB - OBJECTIVES: Alarm over the reported high failure rates for metal-on-metal (MoM)
hip implants as well as their potential for locally aggressive Adverse Reactions
to Metal Debris (ARMDs) has prompted government agencies, internationally, to
recommend the monitoring of patients with MoM hip implants. Some have advised
that a blood ion level >7 ug/L indicates potential for ARMDs. We report a
systematic review and meta-analysis of the performance of metal ion testing for
ARMDs. METHODS: We searched MEDLINE and EMBASE to identify articles from which it
was possible to reconstruct a 2 * 2 table. Two readers independently reviewed all
articles and extracted data using explicit criteria. We computed a summary
receiver operating curve using a Bayesian random-effects hierarchical model.
RESULTS: Our literature search returned 575 unique articles; only six met
inclusion criteria defined a priori. The discriminative capacity of ion tests was
homogeneous across studies but that there was substantial cut-point
heterogeneity. Our best estimate of the "true" area under curve (AUC) for metal
ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can
state that the probability that metal ion testing is actually clinically useful
with an AUC >= 0.75 is 1.7%. CONCLUSION: Metal ion levels are not useful as a
screening test for identifying high risk patients because ion testing will either
lead to a large burden of false positive patients, or otherwise marginally modify
the pre-test probability. With the availability of more accurate non-invasive
tests, we did not find any evidence for using blood ion levels to diagnose
symptomatic patients.Cite this article: M. Pahuta, J. M. Smolders, J. L. van
Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a
useful test for adverse reactions to metal debris: a systematic review and meta
analysis. Bone Joint Res 2016;5:379-386. DOI: 10.1302/2046-3758.59.BJR-2016
0027.R1.
PMID- 27612919
TI - Preoperative hypoalbuminemia is associated with worse outcomes in colon cancer
patients.
AB - BACKGROUND & AIMS: The National Veterans' Affairs Surgical Risk Study identified
preoperative hypoalbuminemia as an independent risk factor for postoperative
morbidity and mortality. Since that time, few studies have investigated the use
of preoperative markers as tools to risk stratify colon cancer patients. The
purpose of our study is to determine if there is an association between
preoperative hypoalbuminemia and 30-day patient morbidity and mortality in colon
cancer patients using the Targeted-Colectomy American College of Surgeons
National Surgery Quality Improvement Program (ACS-NSQIP). METHODS: Stage I, II,
and III elective colon resections with ileocolostomy or colocolostomy were
identified within the ACS-NSQIP targeted colectomy database from 2012 through
2013. Hypoalbuminemia was defined as albumin <3.5 g/dL. Patients with
hypoalbuminemia were compared to those with a normal albumin level in terms of 30
day morbidity and mortality. The albumin level at which point 30-day morbidity
and mortality increased was identified. RESULTS: A total of 5143 patients met
inclusion criteria; 4397 (85.5%) patients had a normal albumin level while 746
(14.5%) had hypoalbuminemia. Preoperative hypoalbuminemia significantly increased
the risk of 30-day mortality (p < 0.0001). The association of hypoalbuminemia
with 30-day outcomes was more significant in patients who underwent open surgery
and had an intra-abdominal anastomosis. The risk of an adverse event was observed
to increase at an albumin level <=3.1 g/dL. CONCLUSIONS: Preoperative
hypoalbuminemia is associated with an increased risk of early patient morbidity
and mortality in patients undergoing surgery for colon cancer. Preoperative
optimization of this patient population warrants further investigation in order
to prevent delay from surgical intervention to adjuvant therapy.
PMID- 27612920
TI - Determining the accuracy of predictive energy expenditure (PREE) equations in
severely obese adolescents.
AB - BACKGROUND & AIMS: Severe obesity in children and adolescents is now a serious
global health concern. Accurate measurements of resting energy expenditure (REE)
is a key foundation for successful obesity treatment. Clinical dietitians rely
heavily on measured or calculated REE to tailor dietary interventions. Indirect
calorimetry (IC) is the gold standard for measuring REE. However, predictive
resting energy expenditure (PREE) equations are commonly used when IC is
unavailable due to cost or practicality. PREE equations differ based on variables
such as age, gender, weight, and height and selecting the most accurate PREE for
an individual is crucial to avoid over or underestimation of energy requirements.
Published studies investigating the accuracy of PREE equations in obese children
and adolescents have reported inconsistent findings, which likely result from
heterogeneity in the patient populations studied. Accordingly, this study aimed
to (a) assess the accuracy of the published PREE equations in a group of severely
obese (SO) adolescents using IC measurement, and (b) determine if there is a BMI
threshold at which the PREE equations become less accurate. METHODS: SO
adolescents were studied using IC. REE was calculated using nine commonly used
PREE equations. Generalized linear regression equations were used to compare
absolute and relative differences between calculated and measured REE (MREE) for
each PREE equation. Accuracy was calculated as the percentage of subjects with
PREE values within 10 percent of MREE. RESULTS: 226 SO adolescents (mean +/- SD
age: 15.9 +/- 1.9 years; weight: 126.9 +/- 24.5 kg; BMI: 44.9 +/- 8.1 kg/m2)
participated. Mean MREE was 2163 +/- 443 kcal/d. PREE calculated by the Mifflin
equation was the only equation without a statistically significant bias compared
to MREE (mean bias of -23 +/- 307 kcal/d; p = 0.26). Mifflin was also the most
accurate with 61% of individuals within +/-10% of MREE. PREE equations accuracy
was not associated with degree of BMI elevation (31-69 kg/m2). CONCLUSIONS: In
adolescents with severe obesity, the Mifflin equation best predicts REE. This
should be the equation applied when using PREE to optimize nutritional care in
this population.
PMID- 27612921
TI - Pre-fracture nutritional status is predictive of functional status at discharge
during the acute phase with hip fracture patients: A multicenter prospective
cohort study.
AB - BACKGROUND & AIMS: Malnutrition is common in patients with hip fractures, and
elderly patients with hip fractures lose functional independence and often fail
to recover previous functional status. The aim of this study was to determine
whether pre-fracture nutritional status predicts functional status of patients
with hip fracture at discharge from acute hospitals. METHODS: In the present
multicenter prospective cohort study, pre-fracture nutritional status was
assessed using the Mini Nutritional Assessment Short-Form (MNA-SF). At discharge
from acute hospitals, functional status was evaluated using a functional
independent measurement instrument (FIM). Subsequently, multiple regression
analyses were performed using FIM as the dependent variable and MNA-SF as the
independent variable. RESULTS: Among the 204 patients analyzed in the present
study, the mean length of hospital stay was 26.2 +/- 12.6 days, and according to
MNA-SF assessments, 51 (25.0%) patients were malnourished, 98 (48.0%) were at
risk of malnutrition, and 55 (27.0%) were well-nourished before fracture. At
discharge, FIM scores were higher in patients who were well-nourished than in
those who were malnourished or were at risk of malnutrition (p < 0.01). After
adjustment for confounding factors, multiple regression analyses showed that MNA
SF was a significant independent predictor for FIM at discharge (well-nourished
vs. malnourished, beta = -0.86, p < 0.01). CONCLUSIONS: Pre-fracture nutritional
status was a significant independent predictor for functional status at discharge
during the acute phase, warranting early assessment of nutritional status and
early intervention for successful postoperative rehabilitation.
PMID- 27612922
TI - Comparison of Dexamethasone Intravitreal Implant with Conventional Triamcinolone
in Patients with Postoperative Cystoid Macular Edema.
AB - AIMS: To evaluate the efficacy of the treatment with intravitreal triamcinolone
acetonide or dexamethasone intravitreal implant in patients with postoperative
cystoid macular edema (PCME). MATERIALS AND METHODS: Thirty eyes of 29 patients
with PCME were randomized into two groups: one group initially received an
injection of 4 mg triamcinolone; retreatment after 3 months was dependent on
functional and anatomic outcome in a PRN regimen. The second group received a
single injection of the dexamethasone intravitreal implant (Ozurdex). Patients
were followed for 6 months. The main outcomes were best-corrected visual acuity
(BCVA) and central millimeter retinal thickness (CMMT). RESULTS: Mean BCVA
improved significantly in both groups at 3 months (p <= 0.05) and 6 months (p <=
0.05) after treatment. There was no statistically significant difference between
the two groups in visual acuity improvement at 3 months (p > 0.05) or 6 months (p
> 0.05). Mean CMMT of both groups also decreased significantly after treatment at
3 and 6 months (both p <= 0.05) and the reduction was significantly superior in
the triamcinolone group compared to ozurdex group at 1 week and 6 months (p <=
0.05). All cases with intraocular hypertension were managed with IOP-lowering
medication and no surgery was required during the study. One patient was excluded
because of endophthalmitis in the triamcinolone group. CONCLUSION: Intravitreal
triamcinolone and dexamethasone implant are both equally effective in increasing
visual acuity in patients with PCME at a 6-month follow-up. However, macular
edema seems to respond more rapidly with intravitreal triamcinolone, and 3
monthly repetitive injections maintain the reduction in retinal thickness better
than a single dexamethasone implant at the first 6 months of follow-up period.
PMID- 27612923
TI - Rectal indomethacin is protective against post-ERCP pancreatitis in high-risk
patients but not average-risk patients: a systematic review and meta-analysis.
AB - BACKGROUND AND AIMS: Rectal indomethacin is a popular chemopreventive agent to
help prevent post-ERCP pancreatitis (PEP). Previous meta-analyses have shown an
overall protective effect for PEP in average-risk and high-risk patients.
However, these meta-analyses are limited by a small number of studies. Recently,
more trials have been published addressing this issue. The aim is to determine
whether rectal indomethacin prevents PEP in average-risk and high-risk groups,
after incorporating these new data. METHODS: A comprehensive search of multiple
literature databases in April 2016 was performed. Human prospective randomized
controlled trials with placebo controls that examined the effect of rectally
administered indomethacin on the incidence of PEP were included. RESULTS: A total
of 8 trials between 2007 and 2016 (n = 3778) were included. No significant
publication bias existed. All studies used similar criteria to detect
pancreatitis. Random effects model meta-analysis showed that the rate of PEP was
significantly lower using indomethacin compared with placebo (relative risk,
0.43; 95% confidence interval, 0.28-0.65; P < .001) in high-risk patients. There
was no significant statistical or clinical heterogeneity. Among average-risk
patients, the rate of PEP was similar (non-significant) between the indomethacin
and placebo groups (relative risk, 0.74; 95% confidence interval, 0.52-1.07; P =
.115). The result of the main outcome remained robust in multiple sensitivity
analyses. CONCLUSIONS: Rectal indomethacin given before or after ERCP is
protective against PEP in high-risk patients versus placebo; however, it is not
protective in average-risk patients versus placebo.
PMID- 27612924
TI - Per-oral endoscopic tunneling for restoration of the esophagus: a novel
endoscopic submucosal dissection technique for therapy of complete esophageal
obstruction.
AB - BACKGROUND AND AIMS: Total aphagia from complete esophageal obstruction (CEO) can
be seen in patients with head-neck or thoracic malignancies undergoing
chemoradiation or surgery. Combined antegrade and retrograde endoscopy (via
gastrostomy tube [G-tube] tract) is often performed for esophageal reconstruction
but is limited by the length of the obstructed esophagus. We describe per-oral
endoscopic tunneling for restoration of the esophagus (POETRE) for patients with
longer segments of esophageal obstruction. The aim of this study was to assess
the efficacy and safety of POETRE for CEO. METHODS: All patients with CEO
undergoing endoscopy with POETRE from October 2013 to September 2015 were
enrolled in this single-center prospective study. Clinical, endoscopic, and
radiologic records were maintained as required for clinical care and for the
study. Dysphagia score was recorded before and after POETRE. Adverse events were
assessed based on the American Society for Gastrointestinal Endoscopy criteria.
RESULTS: Four patients (3 men; mean age, 72.3 years) underwent POETRE for CEO >=3
cm in length. Esophageal reconstruction was technically successful in all
patients (100%). Antegrade submucosal tunneling was performed in 2 of 4 patients
(50%), and retrograde tunneling was performed in the other 2 patients, all with
simultaneous dual endoscope and fluoroscopic guidance. The mean dysphagia score
of 4 before the procedure improved to 2.5 after POETRE during follow-up (mean,
27.8 weeks). All patients required subsequent serial endoscopic dilations as
needed after POETRE. One adverse event (pneumonia) was seen (25%). CONCLUSIONS:
We present a novel ESD technique, POETRE, for therapy of complete esophageal
obstruction. This approach is specifically useful for lumen restoration in
patients with longer segments of esophageal obstruction. (Clinical trial
registration number: NCT00968552.).
PMID- 27612925
TI - Isolation and attempted cultivation of an Anaplasma marginale strain from
Brazilian brown brocket deer (Mazama gouazoubira, Fisher, 1814) in the tick cell
line IDE8.
AB - The aim of the study was to isolate and establish an Anaplasma marginale strain
from Brazilian brown brocket deer, Mazama gouazoubira, in the Ixodes scapularis
cell line IDE8. Blood from a free-living adult female M. gouazoubira naturally
infected with A. marginale (MGI5) was inoculated intravenously into a
splenectomized calf. When A. marginale rickettsemia was 2.5%, blood was collected
and cryopreserved in liquid nitrogen with dimethylsulfoxide (DMSO). IDE8 cell
cultures were infected with calf blood inoculated with the A. marginale (MG15)
isolate. The cultures were monitored by examination of Giemsa-stained
cytocentrifuge smears. Light microscopy of stained IDE8 samples revealed the
first inclusions of A. marginale (MGI5) at 48days post-inoculation (d.p.i). The
IDE8-infected cells contained parasitophorous vacuoles with amorphous material
and a few cocci-like organisms. A sample from IDE8-infected cells from the 16th
subculture (336 d.p.i.) was analyzed by nPCR, nucleotide sequencing, electron
microscopy, and an indirect fluorescent antibody test (IFAT). The IFAT
highlighted some IDE8-infected cells with intense fluorescence in the
parasitophorous vacuole, while in other cells, fluorescence was observed only at
the periphery. DNA from a culture of the MG15 isolate was amplified with A.
marginale msp4 gene primers, and nucleotide sequencing of the PCR product and
BLAST software analysis further confirmed 100% identity with the MGI5 blood
isolate (GenBank no. JN022558.1). Electron microscopy revealed increased numbers
of lysosomes in the cytoplasm of IDE8 cells. Several cells exhibited large
vacuoles containing cellular debris and amorphous material. After the 29th
subculture, it was not possible to detect compatible Anaplasma structures by
light microscopy, and subculture samples tested negative in nPCR. Despite the
failure of the attempt to establish A. marginale (MGI5) in IDE8 cells, the
results demonstrated the isolate's ability to infect, survive and multiply,
although in limited numbers, in IDE8 cells.
PMID- 27612926
TI - Fishes as indicators of untreated sewage contamination in a Mexican coastal
lagoon.
AB - Lagoons are important nursery habitats for fishes but are often sites of intense
human activity including wastewater discharges. The goal of this research was to
compare stable nitrogen (delta15N) and carbon (delta13C) isotopes, total mercury
(THg) and other metal levels in four selected fish species among sites with
different levels of untreated sewage discharge inside Barra de Navidad coastal
lagoon in the Mexican Pacific. Three species from sites heavily impacted by
sewage showed higher delta15N and delta13C compared to those from non-impacted
sites. In addition, the highest concentrations of THg were present in fish of two
species (Sciades guatemalensis and Diapterus brevirostris) collected at the two
most impacted sites, and exceeded the 0.2MUg/g ww threshold believed to be
protective of adult and juvenile fish. No individuals of Achirus mazatlanus and
Mugil curema exceeded this threshold, and liver somatic index and condition did
not distinguish high from low impacted sites for all species. In general, the
metal levels differed among species but not sites, and were lower than what has
been measured in fishes elsewhere. The study also provides the first information
on several fish species for coastal areas of Mexico, suggests that THg and
isotopes can distinguish sewage-impacted sites, and can serve as a baseline for
future studies.
PMID- 27612927
TI - Mercury isotope fractionation during transfer from post-desulfurized seawater to
air.
AB - Samples of dissolved gaseous mercury (DGM) in the post-desulfurized seawater
discharged from a coal-fired power plant together with samples of gaseous
elemental mercury (GEM) over the post-desulfurized seawater surface were
collected and analyzed to study the mercury isotope fractionation during transfer
from post-desulfurized seawater to air. Experimental results showed that when DGM
in the seawater was converted to GEM in the air, the delta202Hg and Delta199Hg
values were changed, ranging from -2.98 to -0.040/00 and from -0.31 to 0.640/00,
respectively. Aeration played a key role in accelerating the transformation of
DGM to GEM, and resulted in light mercury isotopes being more likely to be
enriched in the GEM. The ratio Delta199Hg/Delta201Hg was 1.626 in all samples,
suggesting that mercury mass independent fractionation occurred owing to the
nuclear volume effect during the transformation. In addition, mass independent
fractionation of mercury even isotopes was found in the GEM above the post
desulfurized seawater surface in the aeration pool.
PMID- 27612928
TI - Analysis of banned veterinary drugs and herbicide residues in shellfish by liquid
chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-tandem
mass spectrometry (GC/MS/MS).
AB - Seafood safety is a crucial public health concern for consumers. In this study,
we applied a validated method to analyze the residue of banned veterinary drugs
in shellfish, namely chloramphenicol, malachite green, leucomalachite green, and
nitrofuran metabolites; additionally, the QuEChERS method was employed to detect
76 herbicides by LC/MS/MS and GC/MS/MS. In total, 42 shellfish samples, which
included hard clams, freshwater clams, and oysters, were collected from aquafarms
and production areas in Taiwan during 2012. Our results revealed 3.8ng/g of
chloramphenicol in one hard clam, 19.9-32.1ng/g of ametryn in two hard clams,
16.1-60.1ng/g of pendimethalin in four hard clams, and 17.0ng/g of mefenacet in
one oyster, indicating that 19.1% of the samples contained residues from banned
veterinary drugs and pesticides. These data can be used to monitor the residue of
veterinary drugs and pesticides in aquatic organisms and as a reference for food
safety.
PMID- 27612929
TI - Effects of anthropogenic activities in a Mediterranean coastland: the case study
of the Falerno-Domitio littoral in Campania, Tyrrhenian Sea (southern Italy).
AB - The environmental status of the Falerno-Domitio littoral, a sector of the Italian
south coast (Campania region) locally affected by an extensive anthropic pressure
and pollution, was assessed by a multi-disciplinary approach, consisting of
geological vs. biological studies. Geochemical abundance of potentially hazardous
trace metals in beach sands is mainly constrained by the nature of the source
rocks. Geochemical data of marine sediment quality with regards to possible heavy
metal pollution and the enrichment factors of selected potentially toxic metals
show that Cr and V values are higher in marine samples than in natural sources,
suggesting that they are, at least in part, of anthropic derivation. A
relationship between meiobenthos and heavy metals (Cr, Co, and V) has been also
observed, providing a valuable biological marker to human-deriving chemical
pollution. Ecotoxicological analyses confirm a relationship between enrichment in
selected metals and moderate toxicity of some sea-bottom sediments closer to the
coastline.
PMID- 27612930
TI - Mercury concentrations in Alaska Pacific halibut muscle relative to stable
isotopes of C and N and other biological variables.
AB - Total mercury concentrations ([THg]), delta15N and delta13C values were
determined in muscle of 693 Pacific halibut caught in International Pacific
Halibut Commission setline surveys in Alaska (2002-2011). Project goals were to
evaluate whether 1) delta15N and delta13C varied with region, age, sex and length
of halibut, and 2) muscle [THg] varied with delta15N and delta13C (feeding
ecology) while accounting for sex, length, and region. Variation in [THg] was
explained, in part, by halibut feeding ecology as [THg] increased with trophic
position (increasing delta15N). Halibut from the western Aleutian Island region
were the exception, with overall lower delta15N values and significantly higher
[THg] than halibut from other Alaskan waters. This [THg] pattern has been
observed in other Aleutian biota, possibly the result of northeasterly
atmospheric movement of mercury emissions from Asia and/or other local sources
and processes. The significantly lower delta15N values for these halibut warrants
further investigation of halibut prey.
PMID- 27612931
TI - Accuracy and Trending Ability of the Fourth-Generation FloTrac/Vigileo System in
Patients With Low Cardiac Index.
AB - OBJECTIVES: To determine the accuracy and trending ability of the fourth
generation FloTrac/Vigileo in patients with low cardiac index by comparing
FloTrac/Vigileo-derived cardiac index with that measured by 3-dimensional
echocardiography. DESIGN: Prospective clinical study. SETTING: Cardiac surgery
operating room in a single cardiovascular center. PARTICIPANTS: Twenty-five
patients undergoing elective cardiac resynchronization therapy lead implantation.
INTERVENTIONS: FloTrac/Vigileo-derived cardiac index and 3-dimensional
echocardiography-derived cardiac index were determined simultaneously before and
after phenylephrine bolus and cardiac resynchronization therapy using 3
dimensional echocardiography-derived cardiac index as the reference method.
MEASUREMENTS AND MAIN RESULTS: Cardiac index measured by the fourth-generation
FloTrac/Vigileo had a wide limit of agreement with that measured by 3-dimensional
echocardiography, with a percentage error of 59.1%. The tracking ability of the
unit after both phenylephrine administration and cardiac resynchronization
therapy were measured by concordance rate, and both were below the acceptable
limit (72.7% and 85%, respectively). CONCLUSIONS: The degree of accuracy of the
fourth-generation FloTrac/Vigileo in patients with low cardiac index was not
acceptable, and high systemic vascular resistance in patients with low cardiac
index may have contributed to this inaccuracy. The tracking ability of the fourth
generation FloTrac/Vigileo after phenylephrine administration or cardiac
resynchronization therapy was below acceptable limits.
PMID- 27612932
TI - Program Use and Outcome Change in a Web-Based Trauma Intervention: Individual and
Social Factors.
AB - BACKGROUND: Insight into user adherence to Web-based intervention programs and
into its relationship to intervention effect is needed. OBJECTIVE: The objective
of this study was to examine use of a Web-based self-help intervention program,
the Chinese version of My Trauma Recovery (CMTR), among Chinese traumatized
individuals, and to investigate the relationship between program use and user
characteristics before the intervention and change in outcomes after the
intervention and at 3-months' follow-up. METHODS: The sample consisted of 56
urban survivors of different trauma types and 90 rural survivors of the 2008
Sichuan earthquake, who used the CMTR in 1 month on their own or guided by
volunteers in a counseling center. Predictors were demographics (sex, age,
highest education, marital status, and annual family income), health problems
(trauma duration, posttraumatic symptoms, and depression), psychological factors
(coping self-efficacy), and social factors (social functioning impairment and
social support). Program use was assessed by general program usage (eg, number of
visiting days) and program adherence (eg, webpages completed in modules). Outcome
measures were the Posttraumatic Diagnostic Scale (PDS), Symptom Checklist 90
Depression (SCL-D), Trauma Coping Self-Efficacy scale (CSE), Crisis Support Scale
(CSS), and Social Functioning Impairment questionnaire (SFI) adopted from the
CMTR. RESULTS: (1) Program use: rural participants had a larger total number of
visiting days (F1,144=40.50, P<.001) and visited more program modules in 1 month
(chi(2)3=73.67, P<.001) than urban participants. (2) Predictors and program use:
total number of visiting days was correlated with CSS at pretest (r=.22, P=.009),
and total number of completed webpages was associated with SFI at pretest (r=.19,
P=.02). Number of webpages completed in modules was correlated with all
demographic, disease severity, psychological, and social factors at pretest. (3)
Program use and outcomes change: in general, use of the triggers and self-talk
modules showed a consistent positive association with improvement in PDS, SCL-D,
SFI, and CSE. The relaxation module was associated with positive change in PDS,
but with negative change in CSS and SFI. The professional help module was
associated with positive change in SCL-D, but its use on the first day was
associated with negative change in CSS and CSE. The unhelpful coping module was
associated with negative change in SFI. The mastery tools module showed a
consistent association with negative change in PDS and SCL-D. CONCLUSIONS: These
findings suggest that both individual (eg, demographic, health problems,
psychological) and social factors (eg, social functioning, social support) should
be considered when delivering Web-based interventions, particularly in
collectivist cultures. Specific program adherence indicators (eg, webpages
completed in each module, activity types completed), rather than general program
usage indicators (eg, total number or time of visiting), should be developed to
examine the effectiveness of various program modules or elements. CLINICAL TRIAL:
Australian New Zealand Clinical Trials Registry: ACTRN12611000951954;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343399 (Archived
by WebCite at http://www.webcitation.org/6G7WyNODk).
PMID- 27612935
TI - Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse
Induced Pluripotent Stem Cells.
AB - Induced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo
to all cardiovascular lineages and are therefore a promising cell source for
cardiac regenerative therapy. However, iPSC lines do not all differentiate into
cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase
competent iPSCs with relatively long telomeres and high expression of the
shelterin-complex protein TRF1 (iPSChighT ) differentiate sooner and more
efficiently into CMs than those with relatively short telomeres and low TRF1
expression (iPSClowT ). Ascorbic acid, an enhancer of cardiomyocyte
differentiation, further increases the cardiomyocyte yield from iPSChighT but
does not rescue the cardiomyogenic potential of iPSClowT . Interestingly,
although iPSCslowT differentiate very poorly to the mesoderm and endoderm
lineages, they differentiate very efficiently to the ectoderm lineage, indicating
that cell fate can be determined by in vitro selection of iPSCs with different
telomere content. Our findings highlight the importance of selecting iPSCs with
ample telomere reserves in order to generate high numbers of CMs in a fast,
reliable, and efficient way. Stem Cells 2017;35:362-373.
PMID- 27612933
TI - Reporting of treatment fidelity in behavioural paediatric obesity intervention
trials: a systematic review.
AB - Behavioural interventions for paediatric obesity are promising, but detailed
information on treatment fidelity (i.e. design, training, delivery, receipt and
enactment) is needed to optimize the implementation of more effective
interventions. Little is known about current practices for reporting treatment
fidelity in paediatric obesity studies. This systematic review, in accordance
with Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines, describes the methods used to report treatment fidelity in randomized
controlled trials. Treatment fidelity was double-coded using the National
Institutes of Health Fidelity Framework checklist. Three hundred articles (N =
193 studies) were included. Mean inter-coder reliability across items was 0.83
(SD = 0.09). Reporting of treatment design elements within the field was high
(e.g. 77% of studies reported designed length of treatment session), but
reporting of other domains was low (e.g. only 7% of studies reported length of
treatment sessions delivered). Few reported gold standard methods to evaluate
treatment fidelity (e.g. coding treatment content delivered). General study
quality was associated with reporting of treatment fidelity (p < 0.01) as was the
number of articles published for a given study (p < 0.01). The frequency of
reporting treatment fidelity components has not improved over time (p = 0.26).
Specific recommendations are made to support paediatric obesity researchers in
leading health behaviour disciplines towards more rigorous measurement and
reporting of treatment fidelity.
PMID- 27612936
TI - Prevalence of allergic disease in Old Order Mennonites in New York.
PMID- 27612934
TI - The social patterning of risk factors for noncommunicable diseases in five
countries: evidence from the modeling the epidemiologic transition study (METS).
AB - BACKGROUND: Associations between socioeconomic status (SES) and risk factors for
noncommunicable diseases (NCD-RFs) may differ in populations at different stages
of the epidemiological transition. We assessed the social patterning of NCD-RFs
in a study including populations with different levels of socioeconomic
development. METHODS: Data on SES, smoking, physical activity, body mass index,
blood pressure, cholesterol and glucose were available from the Modeling the
Epidemiologic Transition Study (METS), with about 500 participants aged 25-45 in
each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States).
RESULTS: The prevalence of NCD-RFs differed between these populations from five
countries (e.g., lower prevalence of smoking, obesity and hypertension in rural
Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in
men and of obesity in women in most populations). Smoking and physical activity
were associated with low SES in most populations. The associations of SES with
obesity, hypertension, cholesterol and elevated blood glucose differed by
population, sex, and SES indicator. For example, the prevalence of elevated blood
glucose tended to be associated with low education, but not with wealth, in
Seychelles and USA. The association of SES with obesity and cholesterol was
direct in some populations but inverse in others. CONCLUSIONS: In conclusion, the
distribution of NCD-RFs was socially patterned in these populations at different
stages of the epidemiological transition, but associations between SES and NCD
RFs differed substantially according to risk factor, population, sex, and SES
indicator. These findings emphasize the need to assess and integrate the social
patterning of NCD-RFs in NCD prevention and control programs in LMICs.
PMID- 27612937
TI - A review of caffeine's effects on cognitive, physical and occupational
performance.
AB - Caffeine is consumed by over 80% of U.S. adults. This review examines the effects
caffeine has on cognitive and physical function, since most real-world activities
require complex decision making, motor processing and movement. Caffeine exerts
its effects by blocking adenosine receptors. Following low (~40mg or ~0.5mgkg-1)
to moderate (~300mg or 4mgkg-1) caffeine doses, alertness, vigilance, attention,
reaction time and attention improve, but less consistent effects are observed on
memory and higher-order executive function, such as judgment and decision making.
Effects on physical performance on a vast array of physical performance metrics
such as time-to-exhaustion, time-trial, muscle strength and endurance, and high
intensity sprints typical of team sports are evident following doses that exceed
about 200mg (~3mgkg-1). Many occupations, including military, first responders,
transport workers and factory shift workers, require optimal physical and
cognitive function to ensure success, workplace safety and productivity. In these
circumstances, that may include restricted sleep, repeated administration of
caffeine is an effective strategy to maintain physical and cognitive
capabilities.
PMID- 27612938
TI - Pseudohongiellanitratireducens sp. nov., isolated from seawater, and emended
description of the genus Pseudohongiella.
AB - Two Gram-stain-negative, aerobic, motile by a single polar flagellum and rod
shaped strains, designated SCS-49T and SCS-111, were isolated from seawater of
the South China Sea. The two strains grew at 4-35 degrees C, with 0.5-7.5 %
(w/v) NaCl and at pH 6.5-9.0 and were able to reduce nitrate. Q-8 was the sole
ubiquinone. The major fatty acids of the two strains were C16 : 0, C18 : 1omega7c
and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c). The polar lipids
included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol,
phospoglycolipid, three unidentified glycolipids, five unidentified phospholipids
and two to three unidentified lipids. The isolates formed a stable clade with
Pseudohongiella acticola and Pseudohongiella spirulinae based on phylogenetic
analysis of 16S rRNA gene sequences. Strains SCS-49T and SCS-111 exhibited 16S
rRNA gene sequence similarity values of 97.2 and 96.0 % with respect to the type
strains of P. acticola and P. spirulinae, respectively. The average nucleotide
diversity and in silico DNA-DNA hybridization values between strain SCS-49T and
P. acticola KCTC 42131T were 71.4 and 25.1 %, respectively and the values between
strain SCS-49T and SCS-111 were 99.9 and 99.2 %, respectively. Based upon the
phenotypic, chemotaxonomic and genetic data, strains SCS-49T and SCS-111
represent a novel species in the genus Pseudohongiella, for which the name
Pseudohongiella nitratireducens sp. nov. is proposed. The type strain is SCS-49T
(=CGMCC 1.15425T=KCTC 52155T=MCCC 1K03186T).
PMID- 27612939
TI - The role of the bacterial microbiota on reproductive and pregnancy health.
AB - Recent assessments have examined the composition of bacterial communities
influencing reproductive, pregnancy and infant health. The Microbiome Project has
made great strides in sequencing the microbiome and identifying the vast
communities of microorganisms that inhabit our bodies and much work continues to
examine the individual contribution of bacteria on health and disease to inform
future therapies. This review explores the current literature outlining the
contribution of important bacteria on reproductive health among sexually active
men and women, outlines gaps in current research to determine causal and
interventional relationships, and suggests future research initiatives. Novel
treatments options to reduce adverse outcomes must recognize the heterogeneity of
the bacteria within the microbiome and adequately assess long-term benefits in
reducing disease burden and re-establishing a healthy Lactobacillus-dominant
state. Recognizing other reservoirs outside of the lower genital track and within
sexual partners as well as genetic and individual moderators may be most
important for long-term cure and reduction of disease. It will be important to
develop useful screening tools and comprehensively examine novel therapeutic
options to promote the long-term reduction of high-risk bacteria and the re
establishment of healthy bacterial levels to considerably improve outcomes among
pregnant women and sexually active men and women.
PMID- 27612940
TI - A Method of Radial Nerve Length Measurement Based on Cadaveric Investigation.
AB - OBJECTIVE: To determine the most reliable method to measure the length of the
radial nerve during a nerve conduction study (NCS). DESIGN: Cadaveric
investigation. SETTING: A practical anatomy research laboratory in a university.
PARTICIPANTS: Fresh cadavers (N=10), with 1 cadaver for study design and 9 for
data. INTERVENTIONS: Design of measurement methods using cadaver dissection and
comparison of the measured values to the true length in 18 arms of 9 cadavers.
MAIN OUTCOME MEASURES: Four points (A, B, C, D) were determined: (A) proximal
stimulation point in NCS; (B) point at the elbow crease; (C) point in the
midforearm; and (D) distal stimulation point 5cm above the extensor indicis. The
true length of the radial nerve between the stimulus points (points A and D) in
NCS was compared with the measured values by summation of the straight line
segments between those points with various combinations. The difference in root
mean square error (RMSE) of the distance measured by each method compared with
the true length was calculated to determine the best measurement method. RESULTS:
The closest distance to the true length (28.7+/-2.8cm) in the cadaveric
investigation was obtained using the summation of straight line segments between
points A, B, and D (A-B-D, RMSE=.72cm), followed by the A-B-C-D distance
(RMSE=.87cm) and the A-D distance (RMSE=1.38cm) methods, in sequence. The former
2 distance measurements were relatively closer to the true length than the latter
measurement method. CONCLUSIONS: Multiple segmentation measurement methods
reflected the course of the radial nerve better than a single linear measurement
method. We suggest that the distance measured using a stopover point near the
lateral epicondyle between 2 stimulus points (A-B-D distance) is closer to the
true length of the nerve.
PMID- 27612941
TI - Measuring Community Integration in Persons With Limb Trauma and Amputation: A
Systematic Review.
AB - OBJECTIVES: To conduct a systematic review of community integration measures used
with populations with limb trauma, amputation, or both, and to evaluate each
measure's focus, content, and psychometric properties. DATA SOURCES: Searches of
PubMed and CINAHL for the terms social participation, community integration,
social function, outcome assessment, wounds and injuries, and
amputation/rehabilitation. STUDY SELECTION: Included English-language articles
with a sample size of >=20 adults with limb trauma or amputation. Measures were
deemed eligible if they contained a majority of items related to the construct of
participation as defined by the International Classification of Functioning,
Disability and Health. DATA EXTRACTION: Data on internal consistency; test
retest, interrater, and intrarater reliability; content, structural, construct,
concurrent, and predictive validity; responsiveness; and floor/ceiling effects
were extracted from each article and confirmed by a second investigator. DATA
SYNTHESIS: A total of 156 articles containing 34 measures and 94 subscales were
reviewed. Psychometric properties were rated, and an overall score was calculated
for each measure. Content of the highest scoring measures was examined. Scant
evidence was found regarding the psychometric properties of most measures. Eight
scales from 5 instruments had the strongest measurement properties: the Trinity
Amputation and Prosthesis Experience (TAPES) social restriction and adjustment to
limitation scales; Community Reintegration of Injured Service Members (CRIS)
extent of participation and perceived limitations scales; Medical Outcomes Study
36-Item Short-Form Health Survey (SF-36) role-physical and social functioning
scales; the 136-item Sickness Impact Profile (SIP) psychosocial domain scale; and
the World Health Organization Disability Assessment Schedule 2.0 (WHODAS-II) 12
item total score. CONCLUSIONS: Eights scales from 5 instruments-the TAPES, CRIS,
SF-36, the 136-item SIP, and the WHODAS-II 12-item measure-had the strongest
measurement properties.
PMID- 27612942
TI - beta-Catenin signaling positively regulates glutamate uptake and metabolism in
astrocytes.
AB - BACKGROUND: Neurological disorders have been linked to abnormal excitatory
neurotransmission. Perturbations in glutamate cycling can have profound impacts
on normal activity, lead to excitotoxicity and neuroinflammation, and induce
and/or exacerbate impairments in these diseases. Astrocytes play a key role in
excitatory signaling as they both clear glutamate from the synaptic cleft and
house enzymes responsible for glutamate conversion to glutamine. However,
mechanisms responsible for the regulation of glutamate cycling, including the
main astrocytic glutamate transporter excitatory amino acid transporter 2 (EAAT2
or GLT-1 in rodents) and glutamine synthetase (GS) which catalyzes the ATP
dependent reaction of glutamate and ammonia into glutamine, remain largely
undefined. METHODS: Gain and loss of function for beta-catenin in human
progenitor-derived astrocyte (PDAs) was used to assess EAAT2 and GS levels by
PCR, western blot, luciferase reporter assays, and chromatin immunoprecipitation
(ChIP). Further, morpholinos were stereotaxically injected into C57BL/6 mice and
western blots measured the protein levels of beta-catenin, GLT-1, and GS.
RESULTS: beta-Catenin, a transcriptional co-activator and the central mediator of
Wnt/beta-catenin signaling pathway, positively regulates EAAT2 and GS at the
transcriptional level in PDAs by partnering with T cell factor 1 (TCF-1) and TCF
3, respectively. This pathway is conserved in vivo as the knockdown of beta
catenin in the prefrontal cortex results in reduced GLT-1 and GS expression.
CONCLUSIONS: These studies confirm that beta-catenin regulates key proteins
responsible for excitatory glutamate neurotransmission in vitro and in vivo and
reveal the therapeutic potential of beta-catenin modulation in treating diseases
with abnormal glutamatergic neurotransmission and excitotoxicity.
PMID- 27612944
TI - Postglacial recolonizations, watershed crossings and human translocations shape
the distribution of chub lineages around the Swiss Alps.
AB - BACKGROUND: Distributions of European fish species were shaped by glaciations and
the geological history of river networks until human activities partially
abrogated the restrictions of biogeographical regions. The nearby origins of the
Rhine, Rhone, Danube and Po rivers in the Swiss Alps allow the examination of
historical and human-influenced patterns in fish genetic structure over a small
geographic scale. We investigated these patterns in the widespread European chub
(Squalius cephalus) from the Rhone, Rhine and Danube catchments and its proposed
southern sister species Italian chub (Squalius squalus) from the Po catchment.
RESULTS: A phylogenetic tree constructed from mitochondrial Cytochrome b and COI
sequences was consistent with earlier work in that it showed a separation of
European chub and Italian chub, which was also reflected in microsatellite allele
frequencies, morphological traits and shape differences quantified by geometric
morphometrics. A new finding was that the predominant mitochondrial haplotype of
European chub from the Rhine and Rhone catchments was also discovered in some
individuals from Swiss populations of the Italian chub, presumably as a result of
human translocation. Consistent with postglacial recolonizations from multiple
refugia along the major rivers, the nuclear genetic structure of the European
chub largely reflected drainage structure, but it was modified by watershed
crossings between Rhine and Rhone near Lake Geneva as well as between Danube and
Rhine near Lake Constance. CONCLUSION: Our study adds new insights into the
cyprinid colonization history of central Europe by showing that multiple
processes shaped the distribution of different chub lineages around the Swiss
Alps. Interestingly, we find evidence that cross-catchment migration has been
mediated by unusual geological events such as drainage captures or watershed
crossings facilitated by retreating glaciers, as well as evidence that human
transport has interfered with the historical distribution of these fish (European
chub haplotypes present in the Italian chub). The desirable preservation of
evolutionarily distinct lineages will thus require the prevention of further
translocations.
PMID- 27612943
TI - The Mental Health in Diabetes Service (MINDS) to enhance psychosocial health:
study protocol for a randomized controlled trial.
AB - BACKGROUND: After a diagnosis of diabetes mellitus, people not only have to cope
with the physical aspects and common complications that require daily self
management, they are also faced with ongoing psychosocial challenges.
Subsequently they find themselves having to navigate the health system to engage
multidisciplinary supports; the combination of these factors often resulting in
reduced health-related quality of life. To maintain optimal diabetes control,
interventions need to incorporate psychosocial supports and a skill base for
disease management. Therefore, our aim was to evaluate an 'Optimal Health
Program' that adopts a person-centred approach and engages collaborative therapy
to educate and support the psychosocial health of people diagnosed with type I or
II diabetes. METHODS: This prospective randomised controlled trial will include
166 people diagnosed with diabetes: 83 in the intervention (Optimal Health
Program) and 83 in the control (usual care) group. Participants with type
diabetes mellitus will be recruited through hospital outpatient clinics and
diabetes community organisations. Participants in the intervention group will
receive nine (8 + 1 booster session) sequential sessions, based on a structured
treatment manual emphasising educational and psychosocial support self-efficacy
and skills building. The primary outcome measures will be generalised self
efficacy (GSE) and health-related quality of life (AQoL-6D and EQ-5D). Secondary
measures will be anxiety and depression (HADS), social and workplace functioning
(WSAS), diabetes-related quality of life (DQoL), diabetes-related distress
(PAID), and type of coping strategies (Brief COPE). In addition, a health
economic cost analysis and process evaluations will be performed to assess the
economic cost and efficacy of the program's operations, implementation and
service delivery. DISCUSSION: We envisage that the Optimal Health Program's
emphasis on self-efficacy and self-management will provide participants with the
skills and knowledge to achieve increased empowerment and independence in aspects
of health, which in turn, will help participants deal more effectively with the
physical and psychosocial complexities of diabetes. TRIAL REGISTRATION:
ACTRN12614001085662 . Registered on 10 October 2014.
PMID- 27612945
TI - Comorbid disorders associated with asthma in children in Germany - National
analysis of pediatric primary care data.
AB - BACKGROUND: Using routine healthcare data, the goal of this study was to examine
the association between asthma and comorbid disorders in children in Germany.
METHODS: Patients with a diagnosis of asthma documented by a German pediatrician
in 2015 were identified. Demographic data included age and gender. Patients
younger than 6 and older than 17 and individuals followed for less than a year
before index date were excluded. Each patient was matched for age, sex, and
physician with an asthma-free control. A total of 34,305 cases and 34,305
controls were available for analysis. There were three different age groups: 6-9
years, 10-13 years, and 14-17 years. Several disorders known to be associated
with asthma or found in more than 1% of children and adolescents were also
determined on the basis of primary care diagnoses. A multivariate logistic
regression model was used to estimate the association between asthma and comorbid
disorders. RESULTS: The mean age was 10.9 years, and 61.6% of the subjects were
boys. The most common diseases found in the three age groups were vasomotor and
allergic rhinitis, chronic bronchitis, chronic rhinitis, pneumonia, and atopic
dermatitis. These five comorbid disorders were associated with asthma to a
significant extent. CONCLUSIONS: Overall, this study, based on primary healthcare
data, found a considerably high prevalence of several comorbid diseases in German
children with asthma.
PMID- 27612946
TI - Crop diversity loss as primary cause of grey partridge and common pheasant
decline in Lower Saxony, Germany.
AB - BACKGROUND: The grey partridge (Perdix perdix) and the common pheasant (Phasianus
colchicus) are galliform birds typical of arable lands in Central Europe and
exhibit a partly dramatic negative population trend. In order to understand
general habitat preferences we modelled grey partridge and common pheasant
densities over the entire range of Lower Saxony. Spatially explicit developments
in bird densities were modelled using spatially explicit trends of crop
cultivation. Pheasant and grey partridge densities counted annually by over 8000
hunting district holders over 10 years in a range of 3.7 Mio ha constitute a
unique dataset (wildlife survey of Lower Saxony). Data on main landscape groups,
functional groups of agricultural crops (consisting of 9.5 million fields
compiled by the Integrated Administration and Control System) and landscape
features were aggregated to 420 municipalities. To model linear 8 or 10 year
population trends (for common pheasant and grey partridge respectively) we use
rho correlation coefficients of densities, but also rho coefficients of
agricultural crops. RESULTS: All models confirm a dramatic decline in population
densities. The habitat model for the grey partridge shows avoidance of
municipalities with a high proportion of woodland and water areas, but a
preference for areas with a high proportion of winter grains and high crop
diversity. The trend model confirms these findings with a linear positive effect
of diversity on grey partridge population development. Similarly, the pheasant
avoids wooded areas but showed some preference for municipalities with open
water. The effect of maize was found to be positive at medium densities, but
negative at very high proportions. Winter grains, landscape features and high
crop diversity are favorable. The positive effect of winter grains and higher
crop diversity is also supported by the trend model. CONCLUSIONS: The results
show the strong importance of diverse crop cultivation. Most incentives favor the
cultivation of specific crops, which results in large areas of monocultures. The
results confirm the importance of sustainable agricultural policies.
PMID- 27612947
TI - The evolving management of the appendix mass in the era of laparoscopy and
interventional radiology.
AB - AIM: An appendix mass is the result of a walled-off perforation of the appendix
which localises, resulting in a mass and it is encountered in up to 7% of
patients presenting with acute appendicitis. However, its management is
controversial due to the lack of high level evidence. This review article sets
out a rationale diagnostic and therapeutic strategy for the appendix mass based
upon up-to-date available evidence. METHODS: A literature review of the
investigation and management of appendix mass/complicated appendicitis was
undertaken using PubMed, EMBASE and Google Scholar. RESULTS/CONCLUSION: No
prospective studies were identified. The great majority of recent evidence
supports a conservative management approach avoiding urgent appendicectomy
because of the high risk of major complications and bowel resection. Appendix
abscesses over 5 cm in diameter and persistent abscesses should be drained
percutaneously along with antibiotics. Appendix phlegmon should be treated with
antibiotics alone. Surgery is reserved for patients who fail conservative
treatment. Routine interval appendicectomy is not recommended, but should be
considered in the context of persistent faecolith, ongoing right iliac fossa
pain, recurrent appendicitis and appendix mass persistent beyond 2 weeks.
Clinicians should be particularly wary of patients with appendix mass aged over
40 and those with features suggesting malignancy.
PMID- 27612949
TI - Analytical performance of the BD veritorTM system for rapid detection of
influenza virus A and B in a primary healthcare setting.
AB - BACKGROUND: Infections with influenza A virus cannot be clinically differentiated
from infections caused by influenza B virus or other respiratory viruses.
Additionally, although antiviral treatment is available for influenza A virus, it
is not effective for the other viruses and must be initiated early in the course
of disease for it to be effective. For these reasons, there is a need for a
rapid, accurate diagnostic test for use in physicians' offices at the time
patients are seen. We report the first field performance of BD VeritorTM System
for Rapid Detection of Flu A + B test compared to real time PCR. The performance
of this test was compared to real time PCR performed in the Istanbul University
Influenza Reference Laboratory. METHOD: A single-blinded cross sectional study
was conducted in nine different family medicine centers in Istanbul, Turkey
between 01 November 2014 and 01 May 2015. For every patient, two specimens were
collected, one for real time PCR and one for the Veritor test. Specimens for the
Veritor test were immediately tested at the participating clinic according to the
manufacturer's instructions. The specimens for real time PCR were transferred to
the reference laboratory. RESULTS: A total of 238 persons were included in the
study: 72 (30 %) of the patients included in the study were below 19 years old
and accepted as childhood group. Mean age of adults was 42.4 and children 10.2
years. A total of 122 patients out of 238 were positive for influenza. The
clinical sensitivity and specificity of the Veritor test in all age groups was
determined to be 80 and 94 %, respectively. Positive predictive value was 93 %
and the negative one was 81 %. CONCLUSION: Field performance of the rapid
influenza test was high and found to be useful with respect to rational antiviral
use, avoiding unnecessary antibiotic usage and the management of cases by the
family physicians.
PMID- 27612950
TI - Pigmented basal cell carcinoma: increased melanin or increased melanocytes?
AB - BACKGROUND: Studies on the precise cause of increased melanization in pigmented
basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause
of melanization is from increased number of melanocytes or increased melanin
pigment, and if there is a difference in the number of melanocytes on different
sun-exposed locations. METHODS: A retrospective review of 45 skin biopsies from
January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC
and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated
antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica
Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA)
was performed on all biopsies. Associations between histopathologic features,
number of melanocytes, location, and specific diagnoses were analyzed by Mann
Whitney U test. RESULTS: The mean melanocyte count per high powered field in
pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun
exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC)
of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. CONCLUSIONS: Pigmented
BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs
irrespective of location. Therefore, the pigment is not only due to increased
melanin, but also due to increased melanocytes.
PMID- 27612948
TI - Secreted trophic factors of mesenchymal stem cells support neurovascular and
musculoskeletal therapies.
AB - Adult mesenchymal stem cells (MSCs) represent a subject of intense experimental
and biomedical interest. Recently, trophic activities of MSCs have become the
topic of a number of revealing studies that span both basic and clinical fields.
In this review, we focus on recent investigations that have elucidated trophic
mechanisms and shed light on MSC clinical efficacy relevant to musculoskeletal
applications. Innate differences due to MSC sourcing may play a role in the
clinical utility of isolated MSCs. Pain management, osteochondral, nerve, or
blood vessel support by MSCs derived from both autologous and allogeneic sources
have been examined. Recent mechanistic insights into the trophic activities of
these cells point to ultimate regulation by nitric oxide, nuclear factor-kB, and
indoleamine, among other signaling pathways. Classic growth factors and cytokines
such as VEGF, CNTF, GDNF, TGF-beta, interleukins (IL-1beta, IL-6, and IL-8), and
C-C ligands (CCL-2, CCL-5, and CCL-23)-serve as paracrine control molecules
secreted or packaged into extracellular vesicles, or exosomes, by MSCs. Recent
studies have also implicated signaling by microRNAs contained in MSC-derived
exosomes. The response of target cells is further regulated by their
microenvironment, involving the extracellular matrix, which may be modified by
MSC-produced matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs.
Trophic activities of MSCs, either resident or introduced exogenously, are thus
intricately controlled, and may be further fine-tuned via implant material
modifications. MSCs are actively being investigated for the repair and
regeneration of both osteochondral and other musculoskeletal tissues, such as
tendon/ligament and meniscus. Future rational and effective MSC-based
musculoskeletal therapies will benefit from better mechanistic understanding of
MSC trophic activities, for example using analytical "-omics" profiling
approaches.
PMID- 27612952
TI - Molecular mechanisms for vascular complications of targeted cancer therapies.
AB - Molecularly targeted anti-cancer therapies have revolutionized cancer treatment
by improving both quality of life and survival in cancer patients. However, many
of these drugs are associated with cardiovascular toxicities that are sometimes
dose-limiting. Moreover, the long-term cardiovascular consequences of these
drugs, some of which are used chronically, are not yet known. Although the scope
and mechanisms of the cardiac toxicities are better defined, the mechanisms for
vascular toxicities are only beginning to be elucidated. This review summarizes
what is known about the vascular adverse events associated with three classes of
novel anti-cancer therapies: vascular endothelial growth factor (VEGF)
inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat
chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in
myeloma therapeutics. Three of the best described vascular toxicities are
reviewed including hypertension, increased risk of acute cardiovascular ischaemic
events and arteriovenous thrombosis. The available data regarding the mechanism
by which each therapy causes vascular complication are summarized. When data are
limited, potential mechanisms are inferred from the known effects of inhibiting
each target on vascular cell function and disease. Enhanced understanding of the
molecular mechanisms of vascular side effects of targeted cancer therapy is
necessary to effectively manage cancer patients and to design safer targeted
cancer therapies for the future.
PMID- 27612951
TI - Patient-specific CFD simulation of intraventricular haemodynamics based on 3D
ultrasound imaging.
AB - BACKGROUND: The goal of this paper is to present a computational fluid dynamic
(CFD) model with moving boundaries to study the intraventricular flows in a
patient-specific framework. Starting from the segmentation of real-time
transesophageal echocardiographic images, a CFD model including the complete left
ventricle and the moving 3D mitral valve was realized. Their motion, known as a
function of time from the segmented ultrasound images, was imposed as a boundary
condition in an Arbitrary Lagrangian-Eulerian framework. RESULTS: The model
allowed for a realistic description of the displacement of the structures of
interest and for an effective analysis of the intraventricular flows throughout
the cardiac cycle. The model provides detailed intraventricular flow features,
and highlights the importance of the 3D valve apparatus for the vortex dynamics
and apical flow. CONCLUSIONS: The proposed method could describe the
haemodynamics of the left ventricle during the cardiac cycle. The methodology
might therefore be of particular importance in patient treatment planning to
assess the impact of mitral valve treatment on intraventricular flow dynamics.
PMID- 27612953
TI - N-glycans of growth factor receptors: their role in receptor function and disease
implications.
AB - Numerous signal-transduction-related molecules are secreted proteins or membrane
proteins, and the mechanism by which these molecules are regulated by glycan
chains is a very important issue for developing an understanding of the cellular
events that transpire. This review covers the functional regulation of epidermal
growth factor receptor (EGFR), ErbB3 and the transforming growth factor beta (TGF
beta) receptor by N-glycans. This review shows that the N-glycans play important
roles in regulating protein conformation and interactions with carbohydrate
recognition molecules. These results point to the possibility of a novel strategy
for controlling cell signalling and developing novel glycan-based therapeutics.
PMID- 27612954
TI - Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype
heterologous classical swine fever virus challenge.
AB - BACKGROUND: Classical swine fever (CSF) or hog cholera is a highly contagious
swine viral disease. CSF endemic countries have to use routine vaccination with
modified live virus (MLV) vaccines to prevent and control CSF. However, it is
impossible to serologically differentiate MLV vaccinated pigs from those infected
with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit
vaccine that can provide protection against CSFV challenge. We hypothesize that a
vaccine consisting of a suitable adjuvant and recombinant E2 with natural
conformation may induce a similar level of protection as the MLV vaccine.
RESULTS: Our experimental vaccine KNB-E2 was formulated with the recombinant E2
protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion
based adjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized
intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more
control pigs were administered normal saline solution only. Two weeks after the
second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged
with 5 * 10(5) TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml
intranasal). It was found that while control pigs infected with CSFV stopped
growing and developed high fever (>40 degrees C), high level CSFV load in blood
and nasal fluid, and severe leukopenia 3-14 days post challenge, all KNB-E2
vaccinated pigs continued to grow as control pigs without CSFV exposure, did not
show any fever, had low or undetectable level of CSFV in blood and nasal fluid.
At the time of CSFV challenge, only pigs immunized with KNB-E2 developed high
levels of E2-specific antibodies and anti-CSFV neutralizing antibodies.
CONCLUSIONS: Our studies provide direct evidence that pigs immunized with one
dose KNB-E2 can be protected clinically from CSFV challenge. This protection is
likely mediated by high levels of E2-specific and anti-CSFV neutralizing
antibodies.
PMID- 27612955
TI - Lyme Disease Surveillance in New York State: an Assessment of Case
Underreporting.
AB - Despite the mandatory nature of Lyme disease (LD) reporting in New York State
(NYS), it is believed that only a fraction of the LD cases diagnosed annually are
reported to public health authorities. Lack of complete LD case reporting
generally stems from (i) lack of report of provider-diagnosed cases where
supportive laboratory testing is not ordered or results are negative (i.e.
provider underreporting) and (ii) incomplete case information (clinical
laboratory reporting only with no accompanying clinical information) such that
cases are considered 'suspect' and not included in national and statewide case
counts (i.e. case misclassification). In an attempt to better understand LD
underreporting in NYS, a two-part study was conducted in 2011 using surveillance
data from three counties. Case misclassification was assessed by obtaining
medical records on suspect cases and reclassifying according to the surveillance
case definition. To assess provider underreporting, lists of patients for whom
ICD-9-CM code 088.81 (LD) had been used were reported to NYS Department of Health
(NYSDOH). These lists were matched to the NYSDOH case reporting system, and
medical records were requested on patients not previously reported; cases were
then classified according to the case definition. When including both provider
underreporting and case misclassification, approximately 20% (range 18.4-24.6%)
more LD cases were identified in the three-county study area than were originally
reported through standard surveillance. The additional cases represent a minimum
percentage of unreported cases; the true percentage of unreported cases is likely
higher. Unreported cases were more likely to have a history of erythema migrans
(EM) rash and were more likely to be young paediatric cases. Results of the study
support the assertion that LD cases are underreported in NYS. Initiatives to
increase reporting should highlight the importance of reporting clinically
diagnosed EM and be targeted to those providers most likely to diagnose LD,
specifically providers treating paediatric patients.
PMID- 27612957
TI - Substituted 2-hydroxy-N-(arylalkyl)benzamide sensitizes cancer cells to metabolic
stress by disrupting actin cytoskeleton and inhibiting autophagic flux.
AB - N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide
(Compound 6k), was recently isolated during the preparation of amino acids esters
with salicylanilides. We show here that 6k disrupts the dynamics of actin
cytoskeleton in human melanoma cells, affecting processes essential for the
maintenance and expansion of tumours such as cell adhesion, motility,
proliferation, vesicular transport, and autophagic flux. We demonstrated that
inhibition of autophagy by 6k increased the sensitivity of melanoma cells to
metabolic stress induced by rotenone or nutrient starvation and potentiated the
anti-proliferative activity of small molecule multikinase inhibitor sorafenib.
Since autophagy plays an important role in survival of cancer cells subjected to
chemotherapy, the above mentioned properties are interesting from clinical point
of view as 6k could promote metabolic stress within the tumour microenvironment
and potentiate the effect of cytostatics in combination therapy.
PMID- 27612958
TI - The perivascular environment along the vertebral artery governs segment-specific
structural and mechanical properties.
AB - : The vertebral arteries (VAs) are anatomically divided into four segments (V1
V4), which cumulatively transport blood flow through neck and ultimately form the
posterior circulation of the brain. The vital physiological function of these
conduit vessels depends on their geometry, composition and mechanical properties,
all of which may vary among the defined arterial segments. Despite their
significant role in blood circulation and susceptibility to injury, few studies
have focused on characterizing the mechanical properties of VAs, and none have
investigated the potential for segmental variation that could arise due to
distinct perivascular environments. In this study, we compare the passive
mechanical response of the central, juxtaposed arterial segments of porcine VAs
(V2 and V3) via inflation-extension mechanical testing. Obtained experimental
data and histological measures of arterial wall composition were used to adjust
parameters of structure-motivated constitutive models that quantify the passive
mechanical properties of each arterial segment and enable prediction of wall
stress distributions under physiologic loads and boundary conditions. Our
findings reveal significant segmental differences in the arterial wall geometry
and structure. Nevertheless, similar wall stress distributions are predicted in
these neighboring arterial segments if calculations account for their specific
perivascular environments. These findings allow speculation that segmental
differences in wall structure and geometry are a consequence of a previously
introduced principle of optimal operation of arteries, which ensures effective
bearing of physiological load and a favorable mechanical environment for
mechanosensitive vascular smooth muscle cells. STATEMENT OF SIGNIFICANCE: Among
the numerous biomechanical investigations devoted to conduit blood vessels, only
a few deal with vertebral arteries. While these studies provide useful
information that describes the vessel mechanical response, they do not enable
identification of a constitutive formulation of the mechanical properties of the
vessel wall. This is an important distinction, as a constitutive material model
is required to calculate the local stress environment of mechanosensitive
vascular cells and fully understand the mechanical implications of both vascular
injury and clinical intervention. Moreover, segmental differences in the
mechanical properties of the vertebral arteries could be used to discriminate
among distinct modes of injury and disease etiologies.
PMID- 27612959
TI - Design of magnesium alloys with controllable degradation for biomedical implants:
From bulk to surface.
AB - : The combination of high strength, light weight, and natural biodegradability
renders magnesium (Mg)-based alloys promising in orthopedic implants and
cardiovascular stents. Being metallic materials, Mg and Mg alloys made for
scaffolds provide the necessary mechanical support for tissue healing and cell
growth in the early stage, while natural degradation and reabsorption by
surrounding tissues in the later stage make an unnecessarily follow-up removal
surgery. However, uncontrolled degradation may collapse the scaffolds resulting
in premature implant failure, and there has been much research in controlling the
degradation rates of Mg alloys. This paper reviews recent progress in the design
of novel Mg alloys, surface modification and corrosion mechanisms under different
conditions, and describes the effects of the structure, composition, and surface
conditions on the degradation behavior in vitro and in vivo. STATEMENT OF
SIGNIFICANCE: Owing to their unique mechanical properties, biodegradability,
biocompatibility, Mg based biomaterials are becoming the most promising
substitutes for tissue regeneration for impaired bone, vascular and other tissues
because these scaffolds can provide not only ideal space for the growth and
differentiation of seeded cells but also enough strength before the formation of
normal tissues. The most important is that these scaffolds can be fully degraded
after tissue regeneration, which can satisfy the increasing demand for better
biomedical devices and functional tissue engineering biomaterials in the world.
However, the rapid degradation rate of these scaffolds restricts the wide
application in clinic. This paper reviews recent progress on how to control the
degrdation rate based on the relevant corrosion mechanisms through the design of
porous structure, phase structure, grains, and amorphous structure as well as
surface modification, which will be beneficial to the better understanding and
functional design of Mg-based scaffolds for wide clinical applications in tissue
reconstruction in near futures.
PMID- 27612961
TI - From lead optimization to NDA approval for a new antimicrobial: Use of pre
clinical effect models and pharmacokinetic/pharmacodynamic mathematical modeling.
AB - Because of our current crisis of resistance, particularly in nosocomial
pathogens, the discovery and development of new antimicrobial agents has become a
societal imperative. Changes in regulatory pathways by the Food and Drug
Administration and the European Medicines Agency place great emphasis on the use
of preclinical models coupled with pharmacokinetic/pharmacodynamic analysis to
rapidly and safely move new molecular entities with activity against multi
resistant pathogens through the approval process and into the treatment of
patients. In this manuscript, the use of the murine pneumonia system and the
Hollow Fiber Infection Model is displayed and the way in which the mathematical
analysis of the data arising from these models contributes to the robust choice
of dose and schedule for Phase 3 clinical trials is shown. These data and their
proper analysis act to de-risk the conduct of Phase 3 trials for anti-infective
agents. These trials are the most expensive part of drug development. Further,
given the seriousness of the infections treated, they represent the riskiest
element for patients. Consequently, these preclinical model systems and their
proper analysis have become a central part of accelerated anti-infective
development. A final contention of this manuscript is that it is possible to
embed these models and in particular, the Hollow Fiber Infection Model earlier in
the drug discovery/development process. Examples of 'dynamic driver switching'
and the impact of this phenomenon on clinical trial outcome are provided.
Identifying dynamic drivers early in drug discovery may lead to improved decision
making in the lead optimization process, resulting in the best molecules
transitioning to clinical development.
PMID- 27612960
TI - Development of peptide-functionalized synthetic hydrogel microarrays for stem
cell and tissue engineering applications.
AB - : Synthetic polymer microarray technology holds remarkable promise to rapidly
identify suitable biomaterials for stem cell and tissue engineering applications.
However, most of previous microarrayed synthetic polymers do not possess
biological ligands (e.g., peptides) to directly engage cell surface receptors.
Here, we report the development of peptide-functionalized hydrogel microarrays
based on light-assisted copolymerization of poly(ethylene glycol) diacrylates
(PEGDA) and methacrylated-peptides. Using solid-phase peptide/organic synthesis,
we developed an efficient route to synthesize methacrylated-peptides. In
parallel, we identified PEG hydrogels that effectively inhibit non-specific cell
adhesion by using PEGDA-700 (M. W.=700) as a monomer. The combined use of these
chemistries enables the development of a powerful platform to prepare peptide
functionalized PEG hydrogel microarrays. Additionally, we identified a linker
composed of 4 glycines to ensure sufficient exposure of the peptide moieties from
hydrogel surfaces. Further, we used this system to directly compare cell adhesion
abilities of several related RGD peptides: RGD, RGDS, RGDSG and RGDSP. Finally,
we combined the peptide-functionalized hydrogel technology with bioinformatics to
construct a library composed of 12 different RGD peptides, including 6 unexplored
RGD peptides, to develop culture substrates for hiPSC-derived cardiomyocytes
(hiPSC-CMs), a cell type known for poor adhesion to synthetic substrates. 2 out
of 6 unexplored RGD peptides showed substantial activities to support hiPSC-CMs.
Among them, PMQKMRGDVFSP from laminin beta4 subunit was found to support the
highest adhesion and sarcomere formation of hiPSC-CMs. With bioinformatics, the
peptide-functionalized hydrogel microarrays accelerate the discovery of novel
biological ligands to develop biomaterials for stem cell and tissue engineering
applications. STATEMENT OF SIGNIFICANCE: In this manuscript, we described the
development of a robust approach to prepare peptide-functionalized synthetic
hydrogel microarrays. Combined with bioinformatics, this technology enables us to
rapidly identify novel biological ligands for the development of the next
generation of functional biomaterials for stem cell and tissue engineering
applications.
PMID- 27612963
TI - Gephyrin and the regulation of synaptic strength and dynamics at glycinergic
inhibitory synapses.
AB - Glycinergic synapses predominate in brainstem and spinal cord where they modulate
motor and sensory processing. Their postsynaptic mechanisms have been considered
rather simple because they lack a large variety of glycine receptor isoforms and
have relatively simple postsynaptic densities at the ultrastructural level.
However, this simplicity is misleading being their postsynaptic regions regulated
by a variety of complex mechanisms controlling the efficacy of synaptic
inhibition. Early studies suggested that glycinergic inhibitory strength and
dynamics depend largely on structural features rather than on molecular
complexity. These include regulation of the number of postsynaptic glycine
receptors, their localization and the amount of co-localized GABAA receptors and
GABA-glycine co-transmission. These properties we now know are under the control
of gephyrin. Gephyrin is the first postsynaptic scaffolding protein ever
discovered and it was recently found to display a large degree of variation and
regulation by splice variants, posttranslational modifications, intracellular
trafficking and interactions with the underlying cytoskeleton. Many of these
mechanisms are governed by converging excitatory activity and regulate gephyrin
oligomerization and receptor binding, the architecture of the postsynaptic
density (and by extension the whole synaptic complex), receptor retention and
stability. These newly uncovered molecular mechanisms define the size and number
of gephyrin postsynaptic regions and the numbers and proportions of glycine and
GABAA receptors contained within. All together, they control the emergence of
glycinergic synapses of different strength and temporal properties to best match
the excitatory drive received by each individual neuron or local dendritic
compartment.
PMID- 27612962
TI - Role of proneurotensin as marker of paediatric coeliac disease.
AB - Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear
factor kappa B (NF-kappaB) and interleukin (IL)-8 secretion or anti-inflammatory
through epidermal growth factor receptors. NT mRNA is down-regulated in duodenal
biopsies of children with untreated coeliac disease. The aim of this study was to
investigate if plasma pro-NT levels correlated with the degree of intestinal
mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children
with coeliac disease. Fasting plasma samples from 96 children with coeliac
disease and 89 non-coeliac disease controls were analysed for NT precursor
fragment pro-NT 1-117 by a chemiluminometric immunoassay. Pro-NT levels were
compared with NT mRNA from duodenal biopsies, assessed previously with
quantitative polymerase chain reaction (PCR). Illumina core exome arrays were
used for human leucocyte antigen (HLA) typing and the Marsh criteria applied to
score mucosal damage. Tissue TGA was measured by radio binding assay. A general
linear model compared pro-NT levels with diagnosis of coeliac disease, Marsh
score and HLA DQ haplotype. Spearman's rank test was used to compare pro-NT
levels with tTGA, age and duodenal NT mRNA levels, respectively. Plasma pro-NT
levels were elevated in children with coeliac disease (median 23 pmol/l higher, P
= 0.003) and in those with severe intestinal mucosal damage (median 24 pmol/l
higher for >= Marsh 3b versus not, P = 0.0004). Pro-NT levels correlated further
with tTGA (r2 = 0.22, P = 0.002), but not with duodenal NTS mRNA levels (r2 =
0.12, P = 0.14). Pro-NT was not associated with any of the HLA risk-haplotypes.
Elevated peripheral pro-NT levels reflect more severe forms of active coeliac
disease, indicating a potential role of NT in intestinal inflammation.
PMID- 27612964
TI - Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced
inflammation in COPD.
AB - Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive
pulmonary disease (COPD). We investigated whether CS-induced damage-associated
molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to
susceptibility for COPD. Samples, including bronchial brushings, were collected
from young and old individuals, susceptible and nonsusceptible for the
development of COPD, before and after smoking, and used for gene profiling and
airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or
specific DAMPs. BALB/cByJ and DBA/2J mice were intranasally exposed to LL-37 and
mitochondrial (mt)DAMPs. Functional gene-set enrichment analysis showed that CS
significantly increases the airway epithelial gene expression of DAMPs and DAMP
receptors in COPD patients. In cultured AECs, we observed that CSE induces
necrosis and DAMP release, with specifically higher galectin-3 release from COPD
derived compared with control-derived cells. Galectin-3, LL-37, and mtDAMPs
increased CXCL8 secretion in AECs. LL-37 and mtDAMPs induced neutrophilic airway
inflammation, exclusively in mice susceptible for CS-induced airway inflammation.
Collectively, we show that in airway epithelium from COPD patients, the CS
induced expression of DAMPs and DAMP receptors in vivo and the release of
galectin-3 in vitro is exaggerated. Furthermore, our studies indicate that a
predisposition to release DAMPs and subsequent induction of inflammation may
contribute to the development of COPD.
PMID- 27612965
TI - Human lung fibroblasts produce proresolving peroxisome proliferator-activated
receptor-gamma ligands in a cyclooxygenase-2-dependent manner.
AB - Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify
the inflammatory response to injurious stimuli. Here, we use targeted lipidomics
to explore the hypothesis that HLFs also play an active role in the resolution of
inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both
proinflammatory and proresolving prostaglandins (PGs) in conditioned culture
medium from HLFs treated with a proinflammatory stimulus, IL-1beta. Among the
proresolving PGs in the HLF lipidome were several known ligands for peroxisome
proliferator-activated receptor-gamma (PPARgamma), a transcription factor whose
activation in the lung yields potent anti-inflammatory, antifibrotic, and
proresolving effects. Next, we used a cell-based luciferase reporter to confirm
the ability of HLF supernatants to activate PPARgamma, demonstrating, for the
first time, that primary HLFs activated with proinflammatory IL-1beta or
cigarette smoke extract produce functional PPARgamma ligands; this phenomenon is
temporally regulated, COX-2- and lipocalin-type PGD synthase-dependent, and
enhanced by arachidonic acid supplementation. Finally, we used luciferase
reporter assays to show that several of the PGs in the lipidome of activated HLFs
independently activate PPARgamma and/or inhibit NFkappaB. These results indicate
that HLFs, as immune sentinels, regulate both proinflammatory and proresolving
responses to injurious stimuli. This novel endogenous resolution pathway
represents a new therapeutic target for globally important inflammatory diseases
such as chronic obstructive pulmonary disease.
PMID- 27612968
TI - Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai,
China.
AB - The purpose of this study was to investigate the blood levels of methadone in
participants receiving methadone for the treatment of opioid dependence. After
stabilization on methadone for four weeks, blood samples from 95 participants
were collected between treatment weeks 4 and 12, before and after receiving doses
of methadone, and its blood levels were measured. A multiple linear regression
model was used to examine the association between methadone blood levels and the
outcomes of methadone maintenance treatment (MMT). Outcome differences between
participants who had high (>=2) or low (<2) peak-to-trough ratios were also
compared using an independent sample t-test. The blood level of methadone was not
correlated with the clinical outcome of MMT with the moderate range of doses
given. However, the retention of patients who had a free peak-to-trough ratio >2
was significantly poorer than those whose ratio was <2. Thus, monitoring plasma
methadone levels is unlikely to be effective for guiding dosing decisions in
situations where compliance with MMT is already very high or when the methadone
dose is no longer the dominant factor in determining the clinical outcome.
However, monitoring plasma methadone levels is still helpful for guiding the
dosage for patients with a rapid metabolism.
PMID- 27612966
TI - Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway
epithelial responses by inhibition of DUOX1 and EGFR.
AB - Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is
thought to contribute to increased asthma incidence associated with smoking.
Here, we explored the effects of acute acrolein exposure on innate airway
responses to two common airborne allergens, house dust mite and Alternaria
alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 h)
dramatically inhibited innate airway responses to subsequent allergen challenge,
demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL
25, and IL-1alpha. Acrolein and other anti-inflammatory thiol-reactive
electrophiles, cinnamaldehyde, curcumin, and sulforaphane, similarly inhibited
allergen-induced production of these cytokines from human or murine airway
epithelial cells in vitro. Based on our previous observations indicating the
importance of Ca2+-dependent signaling, activation of the NADPH oxidase DUOX1,
and Src/EGFR-dependent signaling in allergen-induced epithelial secretion of
these cytokines, we explored the impact of acrolein on these pathways. Acrolein
and other thiol-reactive electrophiles were found to dramatically prevent
allergen-induced activation of DUOX1 as well as EGFR, and acrolein was capable of
inhibiting EGFR tyrosine kinase activity via modification of C797. Biotin
labeling strategies indicated increased cysteine modification and carbonylation
of Src, EGFR, as well as DUOX1, in response to acrolein exposure in vitro and in
vivo, suggesting that direct alkylation of these proteins on accessible cysteine
residues may be responsible for their inhibition. Collectively, our findings
indicate a novel anti-inflammatory mechanism of CS-derived acrolein and other
thiol-reactive electrophiles, by directly inhibiting DUOX1- and EGFR-mediated
airway epithelial responses to airborne allergens.
PMID- 27612967
TI - Focal adhesion kinase (FAK) and mechanical stimulation negatively regulate the
transition of airway smooth muscle tissues to a synthetic phenotype.
AB - The effects of mechanical forces and focal adhesion kinase (FAK) in regulating
the inflammatory responses of airway smooth muscle (ASM) tissues to stimulation
with interleukin (IL)-13 were investigated. Canine tracheal tissues were
subjected to different mechanical loads in vitro, and the effects of mechanical
load on eotaxin secretion and inflammatory signaling pathways in response to IL
13 were determined. Eotaxin secretion by tissues in response to IL-13 was
significantly inhibited in muscles maintained at a higher (+) load compared with
those at a lower (-) load as assessed by ELISA, and Akt activation was also
reduced in the higher (+) loaded tissues. Conversely the (+) mechanical load
increased activation of the focal adhesion proteins FAK and paxillin in the
tissues. The role of FAK in regulating the mechanosensitive responses was
assessed by overexpressing FAK-related nonkinase in the tissues, by expressing
the FAK kinase-dead mutant FAK Y397F, or by treating tissues with the FAK
inhibitor PF-573228. FAK inactivation potentiated Akt activity and increased
eotaxin secretion in response to IL-13. FAK inhibition also suppressed the
mechanosensitivity of Akt activation and eotaxin secretion. In addition, FAK
inactivation suppressed smooth muscle myosin heavy chain expression induced by
the higher (+) mechanical load. The results demonstrate that the imposition of a
higher mechanical load on airway smooth muscle stimulates FAK activation, which
promotes the expression of the differentiated contractile phenotype and
suppresses the synthetic phenotype and the inflammatory responses of the muscle
tissue.
PMID- 27612973
TI - From big data to rich data: The key features of athlete wheelchair mobility
performance.
AB - Quantitative assessment of an athlete's individual wheelchair mobility
performance is one prerequisite needed to evaluate game performance, improve
wheelchair settings and optimize training routines. Inertial Measurement Unit
(IMU) based methods can be used to perform such quantitative assessment,
providing a large number of kinematic data. The goal of this research was to
reduce that large amount of data to a set of key features best describing
wheelchair mobility performance in match play and present them in meaningful way
for both scientists and athletes. To test the discriminative power, wheelchair
mobility characteristics of athletes with different performance levels were
compared. The wheelchair kinematics of 29 (inter-)national level athletes were
measured during a match using three inertial sensors mounted on the wheelchair.
Principal component analysis was used to reduce 22 kinematic outcomes to a set of
six outcomes regarding linear and rotational movement; speed and acceleration;
average and best performance. In addition, it was explored whether groups of
athletes with known performance differences based on their impairment
classification also differed with respect to these key outcomes using univariate
general linear models. For all six key outcomes classification showed to be a
significant factor (p<0.05). We composed a set of six key kinematic outcomes that
accurately describe wheelchair mobility performance in match play. The key
kinematic outcomes were displayed in an easy to interpret way, usable for
athletes, coaches and scientists. This standardized representation enables
comparison of different wheelchair sports regarding wheelchair mobility, but also
evaluation at the level of an individual athlete. By this means, the tool could
enhance further development of wheelchair sports in general.
PMID- 27612974
TI - Health at hand: A systematic review of smart watch uses for health and wellness.
AB - INTRODUCTION: Smart watches have the potential to support health in everyday
living by: enabling self-monitoring of personal activity; obtaining feedback
based on activity measures; allowing for in-situ surveys to identify patterns of
behavior; and supporting bi-directional communication with health care providers
and family members. However, smart watches are an emerging technology and
research with these devices is at a nascent stage. METHODS: We conducted a
systematic review of smart watch studies that engaged people in their use by
searching PubMed, Embase, IEEE XPlore and ACM Digital libraries. Participant
demographics, device features, watch applications and methods, and technical
challenges were abstracted from included studies. RESULTS: Seventy-three studies
were returned in the search. Seventeen studies published were included. Included
studies were published from 2014 to 2016, with the exception of one published in
2011. Most studies employed the use of consumer-grade smart watches (14/17, 82%).
Patient-related studies focused on activity monitoring, heart rate monitoring,
speech therapy adherence, diabetes self-management, and detection of seizures,
tremors, scratching, eating, and medication-taking behaviors. Most patient
related studies enrolled participants with few exclusion criteria to validate
smart watch function (10/17, 58%). Only studies that focused on Parkinson's
disease, epilepsy, and diabetes management enrolled persons living with targeted
conditions. One study focused on nursing work in the ICU and one focused on CPR
training for laypeople. CONCLUSION: Consumer-grade smart watches have penetrated
the health research space rapidly since 2014. Smart watch technical function,
acceptability, and effectiveness in supporting health must be validated in larger
field studies that enroll actual participants living with the conditions these
devices target.
PMID- 27612975
TI - Network inference from multimodal data: A review of approaches from infectious
disease transmission.
AB - Networks inference problems are commonly found in multiple biomedical subfields
such as genomics, metagenomics, neuroscience, and epidemiology. Networks are
useful for representing a wide range of complex interactions ranging from those
between molecular biomarkers, neurons, and microbial communities, to those found
in human or animal populations. Recent technological advances have resulted in an
increasing amount of healthcare data in multiple modalities, increasing the
preponderance of network inference problems. Multi-domain data can now be used to
improve the robustness and reliability of recovered networks from unimodal data.
For infectious diseases in particular, there is a body of knowledge that has been
focused on combining multiple pieces of linked information. Combining or
analyzing disparate modalities in concert has demonstrated greater insight into
disease transmission than could be obtained from any single modality in
isolation. This has been particularly helpful in understanding incidence and
transmission at early stages of infections that have pandemic potential. Novel
pieces of linked information in the form of spatial, temporal, and other
covariates including high-throughput sequence data, clinical visits, social
network information, pharmaceutical prescriptions, and clinical symptoms
(reported as free-text data) also encourage further investigation of these
methods. The purpose of this review is to provide an in-depth analysis of
multimodal infectious disease transmission network inference methods with a
specific focus on Bayesian inference. We focus on analytical Bayesian inference
based methods as this enables recovering multiple parameters simultaneously, for
example, not just the disease transmission network, but also parameters of
epidemic dynamics. Our review studies their assumptions, key inference parameters
and limitations, and ultimately provides insights about improving future network
inference methods in multiple applications.
PMID- 27612976
TI - A comparison of overall survival with 40 and 50mg/m2 pegylated liposomal
doxorubicin treatment in patients with recurrent epithelial ovarian cancer:
Propensity score-matched analysis of real-world data.
AB - BACKGROUND: In clinical practice, 40mg/m2 of pegylated liposomal doxorubicin
(PLD40) has been used as an initial dosage for treating recurrent epithelial
ovarian cancer (OC) instead of the recommended dose of 50mg/m2 (PLD50). However,
no robust evidence is available to support the use of PLD40. This post-hoc study
aimed to compare the efficacy and safety of initial PLD dosages in propensity
score (P-score)-matched dataset. METHODS: The data source was a PLD postmarketing
surveillance dataset (n=2189) conducted in Japan. Eligibility criteria for the
present study were as follows: recurrent OC, history of chemotherapy, and
treatment with PLD monotherapy at a dosage between 35.5 and 54.4mg/m2. Overall
survival (OS) was compared between PLD50- and PLD40-treated groups using the log
rank test. Incidences of palmar-plantar erythrodysesthesia (PPE) and stomatitis
were also compared between the groups. RESULTS: Overall, 503 matched pairs were
generated using P-score analysis. The median survival time with PLD50 and PLD40
was 383 and 350days, respectively, with a hazard ratio of 1.10 (95% confidence
interval, 0.98-1.26; p=0.211), although the difference was not statistically
significant in the P-score-matched dataset. However, the incidence and severity
of PPE and stomatitis were significantly lower with PLD40. CONCLUSIONS: Our study
showed that the efficacy of PLD did not differ based on initial dosages, but the
risk of adverse events was reduced with PLD40. Considering the balance between
patient benefits and risks, our results support the use of PLD40 in clinical
practice.
PMID- 27612977
TI - Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the
United States.
AB - OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery for the
treatment of advanced ovarian cancer has remained controversial, despite the
publication of two randomized trials comparing this modality with primary
cytoreductive surgery. This study describes temporal trends in the utilization of
neoadjuvant chemotherapy and interval debulking surgery in clinical practice in
the United States. METHODS: We completed a time trend analysis of the National
Cancer Data Base. We identified women with stage IIIC and IV epithelial ovarian
cancer diagnosed between 2004 and 2013. We categorized subjects as having
undergone one of four treatment modalities: primary cytoreductive surgery
followed by adjuvant chemotherapy, neoadjuvant chemotherapy followed by interval
debulking surgery, surgery only, and chemotherapy only. Temporal trends in the
frequency of treatment modalities were evaluated using Joinpoint regression, and
chi2 tests. RESULTS: We identified 40,694 women meeting inclusion criteria, of
whom 27,032 (66.4%) underwent primary cytoreductive surgery and adjuvant
chemotherapy, 5429 (13.3%) received neoadjuvant chemotherapy and interval
surgery, 5844 (15.4%) had surgery only, and 2389 (5.9%) received chemotherapy
only. The proportion of women receiving neoadjuvant chemotherapy and surgery
increased from 8.6% to 22.6% between 2004 and 2013 (p<0.001), and adoption of
this treatment modality occurred primarily after 2007 (95%CI 2006-2009; p=0.001).
During this period, the proportion of women who received primary cytoreductive
surgery and chemotherapy declined from 68.1% to 60.8% (p<0.001), and the
proportion who underwent surgery only declined from 17.8% to 9.9% (p<0.001).
CONCLUSION: Between 2004 and 2013 the frequency of neoadjuvant chemotherapy and
interval surgery increased significantly in the United States.
PMID- 27612978
TI - Impact of a child stimulation intervention on early child development in rural
Peru: a cluster randomised trial using a reciprocal control design.
AB - OBJECTIVE: Stimulation in early childhood can alleviate adverse effects of
poverty. In a community-randomised trial, we implemented 2 home-based
interventions, each serving as an attention control for the other. One group
received an integrated household intervention package (IHIP), whereas the other
group received an early child development (ECD) intervention. The primary
objective of the study was to evaluate the effect of IHIP on diarrhoea and
respiratory infections, the details of which are described elsewhere. Here, we
present the impact of the ECD intervention on early childhood development
indicators. METHODS: In this non-blinded community-randomised trial, an ECD
intervention, adapted from the Peruvian government's National Wawa Wasi ECD
programme, was implemented in 25 rural Peruvian Andean communities. We enrolled
534 children aged 6-35 months, from 50 communities randomised 1:1 into ECD and
IHIP communities. In ECD communities, trained fieldworkers instructed mothers
every 3 weeks over the 12 months study, to stimulate and interact with their
children and to use standard programme toys. IHIP communities received an
improved stove and hygiene promotion. Using a nationally validated ECD evaluation
instrument, all children were assessed at baseline and 12 months later for
overall performance on age-specific developmental milestones which fall into 7
developmental domains. FINDINGS: At baseline, ECD-group and IHIP-group children
performed similarly in all domains. After 12 months, data from 258 ECD-group and
251 IHIP-group children could be analysed. The proportion of children scoring
above the mean in their specific age group was significantly higher in the ECD
group in all domains (range: 12-23%-points higher than IHIP group). We observed
the biggest difference in fine motor skills (62% vs 39% scores above the mean,
OR: 2.6, 95% CI 1.7 to 3.9). CONCLUSIONS: The home-based ECD intervention
effectively improved child development overall across domains and separately by
investigated domain. Home-based strategies could be a promising component of
poverty alleviation programmes seeking to improve developmental outcomes among
rural Peruvian children. TRIAL REGISTRATION NUMBER: ISRCTN28191222; results.
PMID- 27612979
TI - Epidemiology of positive mental health in a national census of children at school
entry.
AB - BACKGROUND: Until now, child mental health promotion efforts have focused
primarily on reducing the prevalence and severity of problems; yet the absence of
mental health problems does not necessarily imply the presence of healthy
psychosocial functioning. We aimed to investigate the epidemiology of child
mental health competence in a full national population of school entrants.
METHODS: The data source was the 2012 Australian Early Development Index, a
national census of early childhood development completed for school entrants by
teachers across Australia (n=275 800). The mental health competence outcome
measure was derived from constructs that focused on children's social and
emotional strengths. Children with mental health competence scores in the top
quintile were compared with the standard population across individual and
community characteristics. RESULTS: Average age at assessment was 5 years 7
months. Higher odds of mental health competence were observed for children who
lived in more advantaged areas (OR 1.62; 99% CI 1.49 to 1.75), had attended
preschool (1.38; 1.25 to 1.51) and demonstrated effective oral communication
skills in the classroom (19.01; 15.62 to 23.13). Indigenous children had lower
odds compared with non-Indigenous children (0.59; 0.54 to 0.64). Children in
disadvantaged areas who attended preschool did not 'catch up' with their more
advantaged peers. CONCLUSIONS: Mental health competence is unequally distributed
across the Australian child population at school entry and is strongly predicted
by measures and correlates of disadvantage. Effective oral communication and
attendance at preschool warrant further investigation as potentially modifiable
factors that may support mental health competence in new school entrants.
PMID- 27612980
TI - Increase in avoidable hospital admissions after the Great East Japan Earthquake.
AB - BACKGROUND: The Great East Japan Earthquake and subsequent tsunami and nuclear
disaster on 11 March 2011 had a short-term influence on the increase in emergency
department visits and hospital admissions due to various diseases. However, it
remains unclear whether the earthquake and tsunami disaster affected the long
term health conditions of people in the affected areas. METHODS: Using a national
inpatient database in Japan, we investigated people's ambulatory care sensitive
conditions (ACSCs), which are defined as conditions for which effective
management and treatment should prevent admission to a hospital. We compared the
number of admissions for ACSCs before-quake (July 2010 to February 2011) with
after-quake (July 2012 to February 2013) periods in the disaster area compared
with other areas using a difference-in-differences design. Linear regression
models with the interaction between periods and areas were used to estimate the
impact of the earthquake on admissions for ACSCs. RESULTS: No significant
difference in difference was seen in preventable ACSCs (where immunisation and
other interventions can prevent illness) or chronic ACSCs (where effective care
can prevent flare-ups), while acute ACSCs (where early intervention can prevent
more serious progression) increased significantly (3.3 admissions per 100 000
population; 95% CI 0.4 to 6.3; p=0.028). CONCLUSIONS: Preventable and chronic
ACSCs may have increased just after the earthquake and then immediately
decreased. However, avoidable admissions due to acute ACSCs remained high in the
long term after the earthquake and tsunami disaster.
PMID- 27612981
TI - Industry support of physician education in the USA.
PMID- 27612982
TI - Anxiety Symptoms and Coping Motives: Examining a Potential Path to Substance Use
Related Problems in Adolescents With Psychopathic Traits.
AB - BACKGROUND: Although the relation between impulsive-irresponsible psychopathic
traits and substance use is well-documented, the path to developing substance use
problems is less understood in adolescents with these characteristics.
OBJECTIVES: To examine the associations between psychopathy, anxiety, and
substance use motives and a mechanism by which anxiety and alcohol and marijuana
coping motives mediate the relation between psychopathic traits and substance use
related problems. METHODS: A sample of 185 at-risk adolescent males from a
residential military-style program reporting past alcohol or marijuana use (M age
= 16.74) participated in the study. RESULTS: Impulsive-Irresponsible psychopathic
traits were uniquely and incrementally predictive of alcohol and marijuana use
related problems and anxiety. Anxiety and coping motives appeared to partially
explain the association between impulsivity-irresponsibility and substance use
related problems. CONCLUSIONS/IMPORTANCE: Findings suggest that youth expressing
impulsive-irresponsible psychopathic traits may engage in problematic substance
use at least partly as a function of heightened anxiety and a subsequent desire
to alleviate distress by using alcohol or marijuana to cope.
PMID- 27612983
TI - Metacognition in Multisensory Perception.
AB - Metacognition - the ability to monitor one's own decisions and representations,
their accuracy and uncertainty - is considered a hallmark of intelligent
behavior. Little is known about metacognition in our natural multisensory
environment. To form a coherent percept, the brain should integrate signals from
a common cause but segregate those from independent causes. Multisensory
perception thus relies on inferring the world's causal structure, raising new
challenges for metacognition. We discuss the extent to which observers can
monitor their uncertainties not only about their final integrated percept but
also about the individual sensory signals and the world's causal structure. The
latter causal metacognition highlights fundamental links between perception and
other cognitive domains such as social and abstract reasoning.
PMID- 27612984
TI - The Naive Utility Calculus: Computational Principles Underlying Commonsense
Psychology: (Trends in Cognitive Sciences 20, 589-604; July 19, 2016).
PMID- 27612985
TI - Cardiometabolic disease in South Asians: A global health concern in an expanding
population.
AB - Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity
worldwide. As an emerging population, South Asians (SAs) bear a
disproportionately high burden of CVD relative to underlying classical risk
factors, partly attributable to a greater prevalence of insulin resistance and
diabetes and distinct genetic and epigenetic influences. While the phenotypic
distinctions between SAs and other ethnicities in CVD risk are becoming
increasingly clear, the biology of these conditions remains an area of active
investigation, with emerging studies involving metabolism, genetic variation and
epigenetic modifiers (e.g., extracellular RNA). In this review, we describe the
current literature on prevalence, prognosis and CVD risk in SAs, and provide a
landscape of translational research in this field toward ameliorating CVD risk in
SAs.
PMID- 27612986
TI - D-dimer measured at first venous thromboembolism is associated with future risk
of cancer.
PMID- 27612987
TI - Upfront autologous stem cell transplantation for newly diagnosed elderly multiple
myeloma patients: a prospective multicenter study.
AB - The feasibility and efficacy of high-dose melphalan followed by autologous
hematopoietic stem cell transplantation in newly diagnosed elderly patients with
multiple myeloma was analyzed prospectively. Fifty-six multiple myeloma patients,
aged 65 years or over, from 6 French centers were studied. The induction therapy
was bortezomib-based in combination with dexamethasone and either thalidomide,
cyclophosphamide or lenalidomide, for 4-6 cycles. Peripheral blood stem cells
were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with
plerixafor if needed. The conditioning regimen consisted of melphalan at 140
mg/m2 in 18 patients (36%) and 200 mg/m2 in 32 (64%). Three months post
autologous hematopoietic stem cell transplantation, a 2-month consolidation phase
with either lenalidomide plus dexamethasone or bortezomib-based combination
therapy was allowed, but maintenance treatment was not given. All but 6 patients
underwent autologous hematopoietic stem cell transplantation and 3 had tandem
transplantations. The treatment-related mortality was 0% at 100 days post
transplantation. Sixty-eight percent received consolidation therapy following
transplantation. The best response achieved was 40% complete response, 36% very
good partial response, and 18% partial response. After a median follow up of 21
months (range 6-31), the estimated progression-free and overall survival rates at
two years were 76% [95%CI: (61.6-94.1)] and 88% [95%CI: (76.7-100)],
respectively. The higher dose of melphalan (200 mg/m2) afforded superior
progression-free and overall survival rates. This prospective study provides
evidence for the safety and efficacy of autologous hematopoietic stem cell
transplantation as a first-line treatment approach in elderly multiple myeloma
patients. (clinicaltrials.gov identifier: 01671826).
PMID- 27612988
TI - Marked overlap of four genetic syndromes with dyskeratosis congenita confounds
clinical diagnosis.
AB - Dyskeratosis congenita is a highly pleotropic genetic disorder. This
heterogeneity can lead to difficulties in making an accurate diagnosis and delays
in appropriate management. The aim of this study was to determine the underlying
genetic basis in patients presenting with features of dyskeratosis congenita and
who were negative for mutations in the classical dyskeratosis congenita genes. By
whole exome and targeted sequencing, we identified biallelic variants in genes
that are not associated with dyskeratosis congenita in 17 individuals from 12
families. Specifically, these were homozygous variants in USB1 (8 families),
homozygous missense variants in GRHL2 (2 families) and identical compound
heterozygous variants in LIG4 (2 families). All patients had multiple somatic
features of dyskeratosis congenita but not the characteristic short telomeres.
Our case series shows that biallelic variants in USB1, LIG4 and GRHL2, the genes
mutated in poikiloderma with neutropenia, LIG4/Dubowitz syndrome and the recently
recognized ectodermal dysplasia/short stature syndrome, respectively, cause
features that overlap with dyskeratosis congenita. Strikingly, these genes also
overlap in their biological function with the known dyskeratosis congenita genes
that are implicated in telomere maintenance and DNA repair pathways.
Collectively, these observations demonstrate the marked overlap of dyskeratosis
congenita with four other genetic syndromes, confounding accurate diagnosis and
subsequent management. This has important implications for establishing a genetic
diagnosis when a new patient presents in the clinic. Patients with clinical
features of dyskeratosis congenita need to have genetic analysis of USB1, LIG4
and GRHL2 in addition to the classical dyskeratosis congenita genes and telomere
length measurements.
PMID- 27612989
TI - Distinct global binding patterns of the Wilms tumor gene 1 (WT1) -KTS and +KTS
isoforms in leukemic cells.
AB - The zinc finger transcription factor Wilms tumor gene 1 (WT1) acts as an oncogene
in acute myeloid leukemia. A naturally occurring alternative splice event between
zinc fingers three and four, removing or retaining three amino acids (+/-KTS), is
believed to change the DNA binding affinity of WT1, although there are
conflicting data regarding the binding affinity and motifs of the different
isoforms. Increased expression of the WT1 -KTS isoform at the expense of the WT1
+KTS isoform is associated with poor prognosis in acute myeloid leukemia. We
determined the genome-wide binding pattern of WT1 -KTS and WT1 +KTS in leukemic
K562 cells by chromatin immunoprecipitation and deep sequencing. We discovered
that the WT1 -KTS isoform predominantly binds close to transcription start sites
and to enhancers, in a similar fashion to other transcription factors, whereas
WT1 +KTS binding is enriched within gene bodies. We observed a significant
overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites
being distinct. Motif discovery revealed distinct binding motifs for the
isoforms, some of which have been previously reported as WT1 binding sites.
Additional analyses showed that both WT1 -KTS and WT1 +KTS target genes are more
likely to be transcribed than non-targets, and are involved in cell
proliferation, cell death, and development. Our study provides evidence that WT1
KTS and WT1 +KTS share target genes yet still bind distinct locations, indicating
isoform-specific regulation in transcription of genes related to cell
proliferation and differentiation, consistent with the involvement of WT1 in
acute myeloid leukemia.
PMID- 27612990
TI - Corrigendum to "A systematic review of the reporting of tinnitus prevalence and
severity" [Hear. Res. 337 (2016) 70-79].
PMID- 27612991
TI - Doxapram Dosing for Apnea of Prematurity Based on Postmenstrual Age and Gender: A
Randomized Controlled Trial.
AB - INTRODUCTION: Doxapram is used as a third-line treatment for apnea unresponsive
to caffeine and continuous positive airway pressure (CPAP) in preterm infants.
OBJECTIVES: The objectives of this study were to compare the effects of dosing
adjusted for gender and postmenstrual age (PMA) (GrA) versus infants' weight
alone (GrW) on doxapram plasma levels, clinical efficacy, and side effects.
METHODS: This was a randomized, double-blind study, including premature infants
for whom optimized caffeine and CPAP therapy for apnea of prematurity had failed.
Failure was defined as the persistence of more than one significant apnea per
hour over an 8-h period. Plasma levels of doxapram and ketodoxapram were measured
with high-performance liquid chromatography (HPLC) 48 h after the onset of
treatment. Dosing aimed to maintain the combined doxapram and ketodoxapram plasma
level in the therapeutic range of 1.5-4 mg/l. Infants were followed-up for 4 days
after the onset of treatment. RESULTS: A total of 85 infants were included: 46 in
GrW (27.7 +/- 1.9 weeks' gestational age [GA]), 39 in GrA (27.9 +/- 1.4 weeks'
GA); available plasma levels showed that 25 of 40 in the GrW group and 27 of 37
in the GrA group had levels within the therapeutic range (p = 0.344). Of note,
plasma level variance was significantly higher in GrW for doxapram + ketodoxapram
(1.87 vs. 0.89; p = 0.028). Clinical efficacy was better in the GrA group, with a
reduction from 32 to 3 of 38 (76 %) infants with significant apnea versus 30 to 5
of 45 (56 %) in the GrW group (p < 0.001). No adverse effects were observed
during the study. CONCLUSIONS: Taking gender and PMA into account for doxapram
dosing did not significantly increase the number of infants with a plasma level
in the therapeutic range. However, it improved plasma level stability and
clinical efficacy without adverse effects. ClinicalTrials.gov number:
NCT00389909.
PMID- 27612992
TI - The comparison of animal models for premature ovarian failure established by
several different source of inducers.
AB - The objective of this study was to compare premature ovarian failure animal
models established by several different source of inducers. Female ICR mice, KM
mice, and SD rats were treated by cyclophosphamide at 120 mg/kg, busulfan at 12
mg/kg, cisplatin at 3 or 4 mg/kg, 4-vinylcyclohexene diepoxide at 160 mg/kg, 35%
galactose food pellet, and tripterygium glycosides at 50 mg/kg, respectively.
Parameters were analyzed by body weight, serum concentration level of related
hormones, ovarian and uterine pathological examination. The results indicated the
body weight of mice increased very slowly following single dose of
cyclophosphamide (p < 0.05) with damaged ovary; repeated doses of cisplatin could
induce body weight significantly decreased (p < 0.01) with a rising trend of
serum LH concentration, declining tendency of serum E2 concentration and injured
ovary and uterus; 4-vinylcyclohexene diepoxide also hindered the mice growing (p
< 0.05) with damaged ovary and uterus; the body weight of mice feed by 35%
galactose food pellet increased slowly (p < 0.05) with dramatically higher serum
concentration level of galactose, albumin, and total protein (p < 0.001) and
injured ovary. Busulfan and tripterygium glycosides did not present obvious
evidences. In conclusion, the inducers presented their respective features in
such animal models and should be appropriately applied in preventive methods.
PMID- 27612993
TI - Quantifying the benefits of using read-across and in silico techniques to fulfill
hazard data requirements for chemical categories.
AB - Substantial benefits are realized through the use of read-across and in silico
techniques to fill data gaps for structurally similar substances. Considerable
experience in applying these techniques was gained under two voluntary high
production volume (HPV) chemical programs - the International Council of Chemical
Associations' (ICCA) Cooperative Chemicals Assessment Programme (with the
cooperation of the Organization of Economic Cooperation and Development) and the
U.S. Environmental Protection Agency's HPV Challenge Program. These programs led
to the compilation and public availability of baseline sets of health and
environmental effects data for thousands of chemicals. The American Cleaning
Institute's (ACI) contribution to these national and global efforts included the
compilation of these datasets for 261 substances. Chemicals that have structural
similarities are likely to have similar environmental fate, physical-chemical and
toxicological properties, which was confirmed by examining available data from
across the range of substances within categories of structurally similar HPV
chemicals. These similarities allowed the utilization of read-across, trend
analysis techniques and qualitative structure activity relationship ((Q)SAR)
tools to fill data gaps. This paper presents the first quantification of actual
benefits resulting from avoided testing through the use of read-across and in
silico tools. Specifically, in the evaluation of these 261 noted substances, the
use of 100,000-150,000 test animals and the expenditures of $50,000,000 to
$70,000,000 (US) were avoided.
PMID- 27612994
TI - A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy.
AB - The Oxford Classification of IgA nephropathy does not account for glomerular
crescents. However, studies that reported no independent predictive role of
crescents on renal outcomes excluded individuals with severe renal insufficiency.
In a large IgA nephropathy cohort pooled from four retrospective studies, we
addressed crescents as a predictor of renal outcomes and determined whether the
fraction of crescent-containing glomeruli associates with survival from either a
>=50% decline in eGFR or ESRD (combined event) adjusting for covariates used in
the original Oxford study. The 3096 subjects studied had an initial mean+/-SD
eGFR of 78+/-29 ml/min per 1.73 m2 and median (interquartile range) proteinuria
of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular
crescents. Overall, crescents predicted a higher risk of a combined event,
although this remained significant only in patients not receiving
immunosuppression. Having crescents in at least one sixth or one fourth of
glomeruli associated with a hazard ratio (95% confidence interval) for a combined
event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all
individuals. Furthermore, having crescents in at least one fourth of glomeruli
independently associated with a combined event in patients receiving and not
receiving immunosuppression. We propose adding the following crescent scores to
the Oxford Classification: C0 (no crescents); C1 (crescents in less than one
fourth of glomeruli), identifying patients at increased risk of poor outcome
without immunosuppression; and C2 (crescents in over one fourth of glomeruli),
identifying patients at even greater risk of progression, even with
immunosuppression.
PMID- 27612995
TI - Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis.
AB - Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche
provides a specialized microenvironment that facilitates fibroblast activation
and proliferation. However, the molecular identity of these fibrogenic niches is
poorly characterized. Here, we determined whether tenascin-C (TNC), an
extracellular matrix glycoprotein, is a component of the fibrogenic niche in
kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected
to unilateral ureteral obstruction or ischemia/reperfusion injury and
predominantly localized at the foci rich in fibroblasts in renal interstitium. In
vitro, TNC selectively promoted renal interstitial fibroblast proliferation,
bromodeoxyuridine incorporation, and the expression of proliferation-related
genes. The mitogenic activity of TNC required the integrin/focal adhesion
kinase/mitogen-activated protein kinase signaling cascade. Using decellularized
extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated
fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation.
Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo
fibroblast proliferation than did scaffolds prepared from healthy kidney.
Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed
injury-induced fibroblast expansion and renal fibrosis. These studies identify
TNC as a major constituent of the fibrogenic niche that promotes fibroblast
proliferation, and illustrate a pivotal role for the TNC-enriched
microenvironment in kidney fibrogenesis.
PMID- 27612996
TI - HDL Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis
Patients.
AB - The cardioprotective effect of HDL is thought to be largely determined by its
cholesterol efflux capacity, which was shown to inversely correlate with
atherosclerotic cardiovascular disease in populations with normal kidney
function. Patients with ESRD suffer an exceptionally high cardiovascular risk not
fully explained by traditional risk factors. Here, in a post hoc analysis in 1147
patients with type 2 diabetes mellitus on hemodialysis who participated in the
German Diabetes Dialysis Study (4D Study), we investigated whether the HDL
cholesterol efflux capacity is predictive for cardiovascular risk. Efflux
capacity was quantified by incubating human macrophage foam cells with apoB
depleted serum. During a median follow-up of 4.1 years, 423 patients reached the
combined primary end point (composite of cardiac death, nonfatal myocardial
infarction, and stroke), 410 patients experienced cardiac events, and 561
patients died. Notably, in Cox regression analyses, we found no association of
efflux capacity with the combined primary end point (hazard ratio [HR], 0.96; 95%
confidence interval [95% CI], 0.88 to 1.06; P=0.42), cardiac events (HR, 0.92;
95% CI, 0.83 to 1.02; P=0.11), or all-cause mortality (HR, 0.96; 95% CI, 0.88 to
1.05; P=0.39). In conclusion, HDL cholesterol efflux capacity is not a prognostic
cardiovascular risk marker in this cohort of patients with diabetes on
hemodialysis.
PMID- 27612997
TI - Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney
Stone Disease.
AB - Intrarenal crystals trigger inflammation and renal cell necroptosis, processes
that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that
TNFRs also have a direct role in tubular crystal deposition and progression of
hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated
tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium
oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot
and mRNA expression analyses in mice yielded consistent data. When fed an oxalate
rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and
Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1
, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition
and tubular damage observed in wild-type mice. Inhibition of TNFR signaling
prevented the induced expression of the crystal adhesion molecules, CD44 and
annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with
the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice
from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for
CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental
initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of
TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy,
such as primary hyperoxaluria.
PMID- 27613000
TI - Comments on "Maternal exposure to extremely low frequency magnetic fields:
Association with time to pregnancy and foetal growth".
PMID- 27612999
TI - Reply to Comment on "Maternal exposure to extremely low frequency magnetic
fields: Association with time to pregnancy and foetal growth".
PMID- 27612998
TI - Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial
Silencing and Improves Kidney Transplant Outcome.
AB - The eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout
evolution, has the unique characteristic of post-translational activation through
hypusination. This modification is catalyzed by two enzymatic steps involving
deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably,
eIF5A may be involved in regulating the lifespan of Drosophila during long-term
hypoxia. Therefore, we investigated the possibility of a link between eIF5A
hypusination and cellular resistance to hypoxia/anoxia. Pharmacologic targeting
of DHPS by N1-guanyl-1,7-diaminoheptane (GC7) or RNA interference-mediated
inhibition of DHPS or DOHH induced tolerance to anoxia in immortalized mouse
renal proximal cells. Furthermore, GC7 treatment of cells reversibly induced a
metabolic shift toward glycolysis as well as mitochondrial remodeling and led to
downregulated expression and activity of respiratory chain complexes, features
characteristic of mitochondrial silencing. GC7 treatment also attenuated anoxia
induced generation of reactive oxygen species in these cells and in normoxic
conditions, decreased the mitochondrial oxygen consumption rate of cultured cells
and mice. In rats, intraperitoneal injection of GC7 substantially reduced renal
levels of hypusinated eIF5A and protected against ischemia-reperfusion-induced
renal injury. Finally, in the preclinical pig kidney transplant model,
intravenous injection of GC7 before kidney removal significantly improved graft
function recovery and late graft function and reduced interstitial fibrosis after
transplant. This unconventional signaling pathway offers an innovative
therapeutic target for treating hypoxic-ischemic human diseases and organ
transplantation.
PMID- 27613002
TI - The air quality and health impacts of domestic trans-boundary pollution in
various regions of China.
AB - Air pollution is one of the most pressing environmental problems in China.
Literature has reported that outdoor air pollution leads to adverse health
problems every year in China. Recent measurement studies found the important
regional nature of particulates in China. Trans-boundary air pollution within
China has yet to be fully understood. This study aimed to comprehensively
understand the processes of domestic trans-boundary air pollution in China and to
apportion the impacts of emissions in different regions on air quality and public
health. We applied a state-of-the-art air quality model to simulate air quality
in China and then adapted a form of integrated concentration-response function
for China to estimate the resultant amount of premature mortality due to
exposures to PM2.5. Our findings show that domestic trans-boundary impacts (TBI),
on average, account for 27% of the total PM2.5 in China. We estimated that
outdoor air pollution caused ~870,000 (95% CI: 130,000-1500,000) premature
mortalities in China in 2010, of which on average 18% are attributed to TBI.
Among all the regions, North China is the largest contributor to TBI due to 41%
of the health impacts of its emissions occurring in other regions. Taiwan (TW) is
the smallest contributor to TBI occurring in China, contributing 2% of the
national TBI, while TBI causes 22% of the premature mortalities due to outdoor
air pollution in TW. Our findings pinpoint the significant impacts of TBI on
public health in China, indicating the need for cross-region cooperation to
mitigate the air quality impacts and the nation's resultant health problems.
PMID- 27613001
TI - Estimating population exposure to ambient polycyclic aromatic hydrocarbon in the
United States - Part II: Source apportionment and cancer risk assessment.
AB - A revised Community Multiscale Air Quality (CMAQ) model was developed to simulate
the emission, reactions, transport, deposition and gas-to-particle partitioning
processes of 16 priority polycyclic aromatic hydrocarbons (PAHs), as described in
Part I of the two-part series. The updated CMAQ model was applied in this study
to quantify the contributions of different emission sources to the predicted PAH
concentrations and excess cancer risk in the United States (US) in 2011. The
cancer risk in the continental US due to inhalation exposure of outdoor
naphthalene (NAPH) and seven larger carcinogenic PAHs (cPAHs) was predicted to be
significant. The incremental lifetime cancer risk (ILCR) exceeds 1*10-5 in many
urban and industrial areas. Exposure to PAHs was estimated to result in 5704 (608
10,800) excess lifetime cancer cases. Point sources not related with energy
generation and the oil and gas processes account for approximately 31% of the
excess cancer cases, followed by non-road engines with 18.6% contributions.
Contributions of residential wood combustion (16.2%) are similar to that of
transportation-related sources (mostly motor vehicles with small contributions
from railway and marine vessels; 13.4%). The oil and gas industry emissions,
although large contributors to high concentrations of cPAHs regionally, are only
responsible of 4.3% of the excess cancer cases, which is similar to the
contributions of non-US sources (6.8%) and non-point sources (7.2%). The power
generation units pose the most minimal impact on excess cancer risk, with
contributions of approximately 2.3%.
PMID- 27613004
TI - Moral learning as intuitive theory revision.
AB - We argue that moral learning, like much of conceptual development more generally,
involves development and change in children's intuitive theories of the world.
Children's intuitive theories involve coherent and abstract representations of
the world, which point to domain-specific, unobservable causal-explanatory
entities. From this perspective, children rely on intuitive sociological theories
(in particular, an abstract expectation that group memberships constrain people's
obligations), and their intuitive psychological theories (including expectations
that mental states motivate individual behavior) to predict, explain, and
evaluate morally-relevant action. Thus, moral learning involves development and
change in each of these theories of the world across childhood, as well as
developmental change in how children integrate information from these two
intuitive theories. This perspective is supported by a series of research studies
on young children's moral reasoning and learning, and compared to other
developmental approaches, including more traditional forms of constructivism and
more recent nativist perspectives.
PMID- 27613003
TI - CD30 and CD30-Targeted Therapies in Hodgkin Lymphoma and Other B cell Lymphomas.
AB - Evolution of cancer therapeutics has resulted in the development of agents with
varying mechanisms of selective target inhibition. One such therapeutic approach
is utilizing antibody-drug conjugates (ADCs), the combination of a cytotoxic
agent linked with a monoclonal antibody, to achieve localization of the target
and internalization of the cytotoxic agent in order to maximize efficacy with
fewer toxicities. This review focuses on CD30 as a therapeutic target and the
development and clinical activity of the ADC brentuximab vedotin in Hodgkin
lymphoma (HL) and other B cell lymphomas.
PMID- 27613007
TI - Expert's comment concerning Grand Rounds case entitled "A case of severe and
rigid congenital thoracolumbar lordoscoliosis with diastematomyelia presenting
with type 2 respiratory failure: managed by staged correction with controlled
axial traction" by V. Kanagaraju et al. (Eur Spine J; doi:10.1007/s00586-014-3624
0).
PMID- 27613005
TI - When Do Adolescents Accept or Defy to Maternal Prohibitions? The Role of Social
Domain and Communication Style.
AB - Drawing upon both Social-Cognitive Domain Theory and Self-Determination Theory,
the goal of the present multi-informant study was to test whether the correlates
of maternal prohibitions depend on what is prohibited (i.e., the content of the
social domain involved), thereby contrasting moral with friendship prohibitions,
as well on how the prohibition is communicated, thereby contrasting an autonomy
supportive with a controlling communication style. In a sample of adolescents (N
= 196; mean age = 13.9 years; 63 % female) and their mothers (N = 185; mean age =
44 years), we first examined mean-level differences between the two domains in
terms of mothers' degree and style of prohibition, as well as on a number of
developmental outcomes (i.e., adolescents' legitimacy perceptions,
internalization, and oppositional defiance). Both adolescents and mothers
reported more maternal involvement in the moral domain (e.g., higher scores for
degree of prohibition and controlling communication style). In addition,
adolescents reported greater perceived legitimacy and less oppositional defiance
in the moral domain (as compared to the friendships domain). Second, we tested
whether associations between degree and style of prohibition and the
developmental outcomes were moderated by social domain. Whereas associations
between degree of prohibition and developmental outcomes either were non
significant or moderated by domain, the associations with communication style
were more domain-invariant, with an autonomy-supportive style generally yielding
an adaptive pattern of correlates and with a controlling style relating to
maladaptive outcomes. The discussion focuses on similarities and differences in
the characteristics and correlates of both types of prohibitions.
PMID- 27613006
TI - The Effects of Childhood and Adolescent Adversity on Substance Use Disorders and
Poor Health in Early Adulthood.
AB - Childhood and adolescent adversity have been shown to predict later mental and
physical health outcomes. Understanding which aspects and developmental timings
of adversity are important, and the mechanisms by which they have their impact
may help guide intervention approaches. A large subset of adolescents (N = 457;
Female 68.9 %) from the 10-year longitudinal Youth Emotion Project was examined
to better understand the associations among childhood/adolescent adversity,
substance use disorder, and later health quality. Adolescent (but not childhood)
adversities were associated with poorer health in late adolescence/early
adulthood, adolescent adversities were associated with subsequent onset of
substance use disorder, and adolescent adversities continued to be associated
with poorer health in late adolescence/early adulthood after accounting for the
variance explained by substance use disorder onset. These associations were
observed after statistically accounting for emotional disorders and socioeconomic
status. Specific domains of adversity uniquely predicted substance use disorder
and poorer health outcomes. In contrast with current recent research, our
findings suggest the association between childhood/adolescent adversity and
poorer health outcomes in late adolescence and emerging adulthood are not
entirely accounted for by substance use disorder, suggesting efforts to curtail
family-based adolescent adversity may have downstream health benefits.
PMID- 27613008
TI - Minimally manipulative extraction of polycystic cervical neurocysticercosis.
AB - CLINICAL HISTORY: Intradural, extramedullary cervical spinal involvement is an
uncommon manifestation of neurocysticercosis. CASE REPORT: A case of a middle
aged man with neurocysticercosis in the intradural extramedullary cervical spine
and brain who originally presented with bilateral paresthesias of his
extremities, with a progressively unsteady gait. Magnetic resonance imaging
revealed cystic enhancing lesions in the brain and cervical region of the spine,
with the largest cyst extending from the posterior fossa through C2, causing
spinal cord compression. The patient underwent surgical resection of the
intradural extramedullary cervical spinal lesions, and he has continued to
improve clinically, with no recurrence of cystic lesions. CONCLUSION: When
examining patients with clinical signs of a spinal mass lesion, the differential
diagnosis should include neurocysticercosis of the spine.
PMID- 27613009
TI - Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic
review and meta-analysis.
AB - PURPOSE: To examine the association between Vitamin D receptor (VDR) gene
polymorphisms and lumbar disc degeneration (LDD) predisposition. METHODS: A
comprehensive literature search was conducted to identify all the relevant
studies. The allele/genotype frequencies were extracted from each study. We
calculated the pooled odds ratios (ORs) and 95 % confidence intervals (CI) to
assess the strength of the association between the VDR gene polymorphisms and LDD
risk. Statistical analysis was performed using RevMan 5.31 software. RESULTS: A
total of 23 case-control studies (1835 cases and 1923 controls) were included in
this systematic review. For the TaqI (rs731236), FokI (rs2228570) and ApaI
(rs7975232) polymorphisms of VDR gene, nine studies, seven studies, and five
studies, were eventually included in the meta-analysis, respectively. There was
no evidence that the VDR gene polymorphisms (TaqI, FokI, ApaI) had significant
associations with LDD risk.(for TaqI allelic comparison, OR = 1.07, 95 % CI 0.81
1.40, p = 0.64; for FokI allelic comparison, OR = 1.23, 95 % CI 0.83-1.82, p =
0.31; for ApaI allelic comparison, OR = 0.79, 95 % CI 0.55-1.14, p = 0.20). For
stratified analyses by ethnicity and study design, no significant associations
were found in Caucasian population and Asian population, as well as the
population-based studies and hospital-based studies under all genetic models.
CONCLUSIONS: TaqI, FokI, and ApaI polymorphisms of VDR gene were not
significantly associated with the predisposition of LDD. Large-scale and well
designed international studies are needed to further analyze this field.
PMID- 27613010
TI - A case report of spondylectomy with circumference reconstruction for aggressive
vertebral hemangioma covering the whole cervical spine (C4) with progressive
spinal disorder.
AB - PURPOSE: To describe the surgical experience of spondylectomy and spinal
reconstruction for aggressive vertebral hemangioma (VH) induced at the C4
vertebra. No reports have described surgical strategy in cases covering an entire
cervical vertebra presenting with progressive myelopathy. METHODS: A 28-year-old
man presented with rapidly progressing skilled motor dysfunction and gait
disorder. The Japanese Orthopedic Association (JOA) score was 6. Radiography
showed a honeycomb appearance for the entire circumference of the C4 vertebra.
Spinal computed tomography and magnetic resonance imaging showed vertebral tumor
with extraosseous extension causing spinal cord compression. Results of
diagnostic imaging were strongly suggestive of VH. Transarterial embolization of
the spinal body branch was performed first to decrease intraoperative bleeding,
followed by cervical posterior fixation to stabilize the unstable segment and
excision biopsy to obtain a definitive diagnosis. After definitive diagnosis of
cavernous hemangioma, two-stage surgery (anterior and posterior) was performed to
complete total spondylectomy and 360 degrees spinal reconstruction. RESULTS:
Despite multiple operations, JOA scores were 8.5 after posterior fixation, 10.5
after anterior surgery, 11 after final surgery and 16 on postoperative day 90.
The patient acquired excellent clinical results without complications and
returned to society. CONCLUSIONS: The present three-stage surgery comprising
fixation, biopsy, and final spondylectomy with circumferential fusion from
anterior and posterior approaches may offer a useful choice for aggressive VH
covering the entire cervical spine with rapidly progressive myelopathy.
PMID- 27613011
TI - Efficacy of intraoperative direct electrical stimulation of the spinal root and
measurement of distal motor latency in lumbar spinal stenosis.
AB - PURPOSE: The measurement of distal motor latency (DML) is an established method
for diagnosing entrapment peripheral neuropathy. DML can also serve as an index
for disease severity and prognosis. We considered that measuring DML could be
useful in estimating the severity of spinal root impairment and predicting
prognosis in patients with lumbar spinal stenosis (LSS). The purpose of this
study was to investigate the efficacy of intraoperative direct electrical
stimulation of the spinal root and the measurement of DML in LSS. METHODS: In 39
patients with LSS, a total of 93 spinal roots were stimulated, and evoked
electromyography was recorded at the leg muscles after decompression. DML was
measured and its correlation with clinical severity, as evaluated by Zurich
claudication questionnaire (ZCQ) and Short Form 36 (SF-36), was investigated.
RESULTS: For the stimulation of the L3, L4, and L5 spinal root, the mean DML (ms)
were 6.8 (+/-1.4), 7.4 (+/-1.3), and 6.0 (+/-1.3) in gluteus medius, 9.3 (+/
1.5), 9.2 (+/-1.5), and 9.0 (+/-1.6) in biceps femoris, 9.7 (+/-1.0), 9.8 (+/
1.8), and 9.4 (+/-1.2) in vastus medialis, 16.1 (+/-1.0), 14.7 (+/-1.3), and 14.1
(+/-1.5) in tibialis anterior, and 16.4 (+/-1.4), 14.3 (+/-1.8), and 13.9 (+/
1.9) in gastrocnemius muscles. Statistically significant positive correlations
were observed between DML and height. Preoperative symptom and function scores of
ZCQ and postoperative bodily pain scores of SF-36 were significantly worse in the
patients with prolonged DML. CONCLUSIONS: DML is thought to be useful for
estimating the severity of spinal root impairment and for predicting the
prognosis.
PMID- 27613012
TI - Proof of concept of a "greener" protein purification/enrichment method based on
carboxylate-terminated carbosilane dendrimer-protein interactions.
AB - Protein sample preparation is a critical and an unsustainable step since it
involves the use of tedious methods that usually require high amount of solvents.
The development of new materials offers additional opportunities in protein
sample preparation. This work explores, for the first time, the potential
application of carboxylate-terminated carbosilane dendrimers to the
purification/enrichment of proteins. Studies on dendrimer binding to proteins,
based on protein fluorescence intensity and emission wavelengths measurements,
demonstrated the interaction between carboxylate-terminated carbosilane
dendrimers and proteins at all tested pH levels. Interactions were greatly
affected by the protein itself, pH, and dendrimer concentration and generation.
Especially interesting was the interaction at acidic pH since it resulted in a
significant protein precipitation. Dendrimer-protein interactions were modeled
observing stable complexes for all proteins. Carboxylate-terminated carbosilane
dendrimers at acidic pH were successfully used in the purification/enrichment of
proteins extracted from a complex sample. Graphical Abstract Images showing the
growing turbidity of solutions containing a mixture of proteins (lysozyme,
myoglobin, and BSA) at different protein:dendrimer ratios (1:0, 1:1, 1:8, and
1:20) at acidic pH and SDS-PAGE profiles of the corresponsing supernatants.
Comparison of SDS-PAGE profiles for the pellets obtained during the purification
of proteins present in a complex sample using a conventional "no-clean" method
based on acetone precipitation and the proposed "greener" method using
carboxylate-terminated carbosilane dendrimer at a 1:20 protein:dendrimer ratio.
PMID- 27613014
TI - Erratum to: Identification of Stachybotrys spp. by MALDI-TOF mass spectrometry.
PMID- 27613015
TI - PM2.5 levels, chemical composition and health risk assessment in Xinxiang, a
seriously air-polluted city in North China.
AB - Seventeen PM2.5 samples were collected at Xinxiang during winter in 2014. Nine
water-soluble ions, 19 trace elements and eight fractions of carbonaceous species
in PM2.5 were analyzed. PM2.5 concentrations and elements species during
different periods with different pollution situations were compared. The threat
of heavy metals in PM2.5 was assessed using incremental lifetime cancer risk.
During the whole period, serious regional haze pollution persisted, and the
averaged concentration of PM2.5 was 168.5 MUg m-3, with 88.2 % of the daily
samples exhibiting higher PM2.5 concentrations than the national air quality
standard II. The high NO3-/SO42- ratio suggested that vehicular exhaust made an
important contribution to atmospheric pollution. All of organic carbon and
elemental carbon ratios in this study were above 2.0 for PM2.5, which might
reflect the combined contributions from coal combustion, motor vehicle exhaust
and biomass burning. Mean 96-h backward trajectory clusters indicated that more
serious air pollution occurred when air masses transported from the Hebei, Shanxi
and Zhengzhou. The concentrations of the water-soluble ions and trace elements on
haze days were 2 and 1.8 times of those on clear days. The heavy metals in PM2.5
might not cause non-cancerous health issues by exposure through the human
respiratory system. However, lifetime cancer risks of heavy metals obviously
exceeded the threshold (10-6) and might have a cancer risk for residents in
Xinxiang. This study provided detailed composition data and comprehensive
analysis of PM2.5 during the serious haze pollution period and their potential
impact on human health in Xinxiang.
PMID- 27613016
TI - Response of an oscillatory differential delay equation to a single stimulus.
AB - Here we analytically examine the response of a limit cycle solution to a simple
differential delay equation to a single pulse perturbation of the piecewise
linear nonlinearity. We construct the unperturbed limit cycle analytically, and
are able to completely characterize the perturbed response to a pulse of positive
amplitude and duration with onset at different points in the limit cycle. We
determine the perturbed minima and maxima and period of the limit cycle and show
how the pulse modifies these from the unperturbed case.
PMID- 27613017
TI - Disentangling narrow and coarse semantic networks in the brain: The role of
computational models of word meaning.
AB - There has been a recent boom in research relating semantic space computational
models to fMRI data, in an effort to better understand how the brain represents
semantic information. In the first study reported here, we expanded on a previous
study to examine how different semantic space models and modeling parameters
affect the abilities of these computational models to predict brain activation in
a data-driven set of 500 selected voxels. The findings suggest that these
computational models may contain distinct types of semantic information that
relate to different brain areas in different ways. On the basis of these
findings, in a second study we conducted an additional exploratory analysis of
theoretically motivated brain regions in the language network. We demonstrated
that data-driven computational models can be successfully integrated into
theoretical frameworks to inform and test theories of semantic representation and
processing. The findings from our work are discussed in light of future
directions for neuroimaging and computational research.
PMID- 27613013
TI - From single molecules to life: microscopy at the nanoscale.
AB - Super-resolution microscopy is the term commonly given to fluorescence microscopy
techniques with resolutions that are not limited by the diffraction of light.
Since their conception a little over a decade ago, these techniques have quickly
become the method of choice for many biologists studying structures and processes
of single cells at the nanoscale. In this review, we present the three main
approaches used to tackle the diffraction barrier of ~200 nm: stimulated-emission
depletion (STED) microscopy, structured illumination microscopy (SIM), and single
molecule localization microscopy (SMLM). We first present a theoretical overview
of the techniques and underlying physics, followed by a practical guide to all of
the facets involved in designing a super-resolution experiment, including an
approachable explanation of the photochemistry involved, labeling methods
available, and sample preparation procedures. Finally, we highlight some of the
most exciting recent applications of and developments in these techniques, and
discuss the outlook for this field. Graphical Abstract Super-resolution
microscopy techniques. Working principles of the common approaches stimulated
emission depletion (STED) microscopy, structured illumination microscopy (SIM),
and single-molecule localization microscopy (SMLM).
PMID- 27613018
TI - The Set of Fear Inducing Pictures (SFIP): Development and validation in fearful
and nonfearful individuals.
AB - Emotionally charged pictorial materials are frequently used in phobia research,
but no existing standardized picture database is dedicated to the study of
different phobias. The present work describes the results of two independent
studies through which we sought to develop and validate this type of database-a
Set of Fear Inducing Pictures (SFIP). In Study 1, 270 fear-relevant and 130
neutral stimuli were rated for fear, arousal, and valence by four groups of
participants; small-animal (N = 34), blood/injection (N = 26), social-fearful (N
= 35), and nonfearful participants (N = 22). The results from Study 1 were
employed to develop the final version of the SFIP, which includes fear-relevant
images of social exposure (N = 40), blood/injection (N = 80), spiders/bugs (N =
80), and angry faces (N = 30), as well as 726 neutral photographs. In Study 2, we
aimed to validate the SFIP in a sample of spider, blood/injection, social
fearful, and control individuals (N = 66). The fear-relevant images were rated as
being more unpleasant and led to greater fear and arousal in fearful than in
nonfearful individuals. The fear images differentiated between the three fear
groups in the expected directions. Overall, the present findings provide evidence
for the high validity of the SFIP and confirm that the set may be successfully
used in phobia research.
PMID- 27613019
TI - An evaluation of scanpath-comparison and machine-learning classification
algorithms used to study the dynamics of analogy making.
AB - In recent years, eyetracking has begun to be used to study the dynamics of
analogy making. Numerous scanpath-comparison algorithms and machine-learning
techniques are available that can be applied to the raw eyetracking data. We show
how scanpath-comparison algorithms, combined with multidimensional scaling and a
classification algorithm, can be used to resolve an outstanding question in
analogy making-namely, whether or not children's and adults' strategies in
solving analogy problems are different. (They are.) We show which of these
scanpath-comparison algorithms is best suited to the kinds of analogy problems
that have formed the basis of much analogy-making research over the years.
Furthermore, we use machine-learning classification algorithms to examine the
item-to-item saccade vectors making up these scanpaths. We show which of these
algorithms best predicts, from very early on in a trial, on the basis of the
frequency of various item-to-item saccades, whether a child or an adult is doing
the problem. This type of analysis can also be used to predict, on the basis of
the item-to-item saccade dynamics in the first third of a trial, whether or not a
problem will be solved correctly.
PMID- 27613020
TI - Cortisol Patterns for Young Children Displaying Disruptive Behavior: Links to a
Teacher-Child, Relationship-Focused Intervention.
AB - Supportive and close relationships that young children have with teachers have
lasting effects on children's behavior and academic success, and this is
particularly true for children with challenging behaviors. These relationships
are also important for children's developing stress response system, and children
in child care may be more likely to display atypical cortisol patterns at child
care. However, warm, supportive relationships with teachers may buffer these
negative effects of child care. While many relationship-focused early childhood
interventions demonstrate changes in child behavior, associations with children's
stress response system are unknown. This study assessed children's activity in
the hypothalamic-pituitary-adrenal axis via salivary cortisol as a function of
their participation in a dyadic intervention intended to improve a teacher's
interaction quality with a particular child. Seventy teachers and 113 preschool
children participated who were part of a larger study of teachers and children
were randomly assigned at the classroom level across three intervention
conditions: Banking Time, Time-Control Comparison (Child Time), and Business-as
Usual. At the end of the school year, children in the Banking Time condition
displayed a significantly greater decline in cortisol across the morning during
preschool compared to children in Business-as-Usual condition. These pilot
results are among the first to provide preliminary evidence that school-based
interventions that promote sensitive and responsive interactions may improve
young children's activity in the stress response system within the child
care/early education context.
PMID- 27613021
TI - [Mucous membran diseases].
PMID- 27613023
TI - [Lesions of the oral mucosa : Differential diagnostic approach from the
maxillofacial surgeon's perspective].
AB - A detailed medical history and a careful clinical examination are the basis for
developing a list of possible differential diagnoses in lesions of the oral
mucosa. On this basis, it can be decided whether a lesion can be observed for 14
days after removal of possible causes or the start of a trial treatment, or
whether a biopsy for histological examination must be taken immediately. An
excisional biopsy is performed for small and presumably benign lesions, an
incisional biopsy for large and presumably malignant lesions. If an autoimmune
blistering disease is suspected, a second sample for examination by
immunofluorescence is taken. Depending on the results of the histological
examination further treatment steps are planned or regular appointments for
follow-up are arranged.
PMID- 27613022
TI - [Actinic keratoses].
AB - Actinic keratosis (AK) is a very common skin diagnosis in office-based
dermatology. Due to the demographic changes with increasing numbers of elderly
people, the proportion of patients with AK is expected rise. In order to avoid
progression into squamous cell carcinoma, early treatment is recommended.
Numerous treatment options are currently available for this purpose. In addition
to targeted therapies for isolated AK many field-directed treatment modalities
are available. However, the treatment option that is finally chosen depends on a
variety of factors (e.g., age of the patient, the extent of the clinical
findings) and the patient's needs and therefore has to be customized.
PMID- 27613024
TI - Bacterial Meningitis in Patients using Immunosuppressive Medication: a Population
based Prospective Nationwide Study.
AB - We studied occurrence, presentation, disease course, effect of adjunctive
dexamethasone, and prognosis of bacterial meningitis in patients using
immunosuppressive medication. Patients were selected from our nationwide,
prospective cohort on community-acquired bacterial meningitis performed from
March 1, 2006 through October 31, 2014. Eighty-seven of 1447 episodes (6 %) of
bacterial meningitis occurred in patients using immunosuppressive medication, and
consisted of corticosteroids in 82 %. Patients with bacterial meningitis using
immunosuppressive medication were less likely to present with headache (P = 0.02)
or neck stiffness (P = 0.005), as compared those not on immunosuppressive
medication. In 46 % of episodes CSF leukocyte count was below 1000/mm3. CSF
cultures revealed S. pneumoniae in 41 % and L. monocytogenes in 40 % of episodes.
Outcome was unfavorable in 39 of 87 episodes (45 %) and death occurred in 22 of
87 episodes (25 %). Adjunctive dexamethasone was administered in 52 of 87 (60 %)
episodes, and mortality tended to be lower in those on adjunctive dexamethasone
therapy as compared to those without dexamethasone therapy (10 of 52 [19 %] vs 12
of 35 [34 %], P = 0.14). We conclude that bacterial meningitis in patients using
immunosuppressive medication is likely to present with atypical clinical and
laboratory features, and is often caused by atypical bacteria, mainly L.
monocytogenes. Adjunctive dexamethasone is widely prescribed in these patients
and was not associated with harm in this study.
PMID- 27613025
TI - Long-term effects of parental divorce timing on depression: A population-based
longitudinal study.
AB - BACKGROUND: We examined the long-term effects of parental divorce timing on
depression using longitudinal data from the Korean Welfare Panel Study. METHODS:
Depression symptoms were measured using the 11 items of Center for Epidemiologic
Scale for Depression (CES-D-11), and we categorized parental divorce timing into
'early childhood', 'adolescent' and 'none'. RESULTS: Although participants who
experienced parental divorce during adolescence exhibited a significantly higher
CES-D-11 score ( p = .0468), 'early childhood' participants displayed the most
increased CES-D-11 score compared to the control group ( p = .0007). Conversely,
among participants who were unsatisfied with their marriage, those who
experienced parental divorce in early childhood showed lower CES-D-11 scores,
while 'adolescent period' participants exhibited significantly higher CES-D-11
scores ( p = .0131). CONCLUSION: We concluded that timing of parental divorce
exerts substantial yet varied effects on long-term depression symptoms and future
marriage satisfaction.
PMID- 27613026
TI - NHS winter pressures are becoming an all year reality, warn experts.
PMID- 27613027
TI - UPS Activation in the Battle Against Aging and Aggregation-Related Diseases: An
Extended Review.
AB - Aging is a biological process accompanied by gradual increase of damage in all
cellular macromolecules, i.e., nucleic acids, lipids, and proteins. When the
proteostasis network (chaperones and proteolytic systems) cannot reverse the
damage load due to its excess as compared to cellular repair/regeneration
capacity, failure of homeostasis is established. This failure is a major hallmark
of aging and/or aggregation-related diseases. Dysfunction of the major cellular
proteolytic machineries, namely the proteasome and the lysosome, has been
reported during the progression of aging and aggregation-prone diseases.
Therefore, activation of these pathways is considered as a possible preventive or
therapeutic approach against the progression of these processes. This chapter
focuses on UPS activation studies in cellular and organismal models and the
effects of such activation on aging, longevity and disease prevention or
reversal.
PMID- 27613028
TI - Review and Literature Mining on Proteostasis Factors and Cancer.
AB - Automatic analysis of increasingly growing literature repositories including data
integration to other databases is a powerful tool to propose hypothesis that can
be used to plan experiments to validate or disprove the hypothesis. Furthermore,
it provides means to evaluate the redundancy of research line in comparison to
the published literature. This is potentially beneficial for those developing
research in a specific disease which are interested in exploring a particular
pathway or set of genes/proteins. In the scope of the integrating book a case
will be made addressing proteostasis factors in cancer. The maintenance of
proteome homeostasis, known as proteostasis, is a process by which cells regulate
protein translation, degradation, subcellular localization, and protein folding
and consists of an integrated network of proteins. The ubiquitin-proteasome
system plays a key role in essential biological processes such as cell cycle, DNA
damage repair, membrane trafficking, and maintaining protein homeostasis. Cells
maintain proteostasis by regulating protein translation, degradation, subcellular
localization, and protein folding. Aberrant proteostasis leads to loss-of
function diseases (cystic fibrosis) and gain-of-toxic-function diseases
(Alzheimer's, Parkinson's, and Huntington's disease). Cancer therapy on the other
hand explores inhibition of proteostasis factors to trigger endoplasmic reticulum
stress with subsequent apoptosis. Alternatively therapies target deubiquitinases
and thereby regulate tumor promoters or suppressors. Furthermore, mutations in
specific proteostasis factors are associated with higher risk for specific
cancers, e.g., BRCA mutations in breast cancer. This chapter discusses
proteostasis protein factors' association with cancer from a literature mining
perspective.
PMID- 27613029
TI - Combining Zebrafish and Mouse Models to Test the Function of Deubiquitinating
Enzyme (Dubs) Genes in Development: Role of USP45 in the Retina.
AB - Ubiquitination is a dynamic and reversible posttranslational modification. Much
effort has been devoted to characterize the function of ubiquitin pathway genes
in the cell context, but much less is known on their functional role in the
development and maintenance of organs and tissues in the organism. In fact,
several ubiquitin ligases and deubiquitinating enzymes (DUBs) are implicated in
human pathological disorders, from cancer to neurodegeneration. The aim of our
work is to explore the relevance of DUBs in retinal function in health and
disease, particularly since some genes related to the ubiquitin or SUMO pathways
cause retinal dystrophies, a group of rare diseases that affect 1:3000
individuals worldwide. We propose zebrafish as an extremely useful and
informative genetic model to characterize the function of any particular gene in
the retina, and thus complement the expression data from mouse. A preliminary
characterization of gene expression in mouse retinas (RT-PCR and in situ
hybridization) was performed to select particularly interesting genes, and we
later replicated the experiments in zebrafish. As a proof of concept, we selected
ups45 to be knocked down by morpholino injection in zebrafish embryos. Morphant
phenotypic analysis showed moderate to severe eye morphological defects, with a
defective formation of the retinal structures, therefore supporting the relevance
of DUBs in the formation and differentiation of the vertebrate retina, and
suggesting that genes encoding ubiquitin pathway enzymes are good candidates for
causing hereditary retinal dystrophies.
PMID- 27613030
TI - Immunodepletion and Immunopurification as Approaches for CSN Research.
AB - The COP9 signalosome (CSN) is an evolutionary conserved complex that is found in
all eukaryotes, and implicated in regulating the activity of Cullin-RING
ubiquitin Ligases (CRLs). Activity of CRLs is highly regulated; complexes are
active when the cullin subunit is covalently attached to the ubiquitin like
modifier, Nedd8. Neddylation/deneddylation cycles are required for proper CRLs
activity, and deneddylation is performed by the CSN complex.We describe here a
method utilizing resin-coupled antibodies to deplete the CSN from human cell
extracts, and to obtain endogenous CSN complexes by immunopurification. In the
first step, the cross-linked primary antibodies recognize endogenous CSN
complexes, and deplete them from cell extract as the extract passes through the
immunoaffinity column. The resulting "CSN-depleted extract" (CDP) is rich in
neddylated cullins that can be used as a substrate for cullin-deneddylation assay
for CSN complexes purified from various eukaryotes. Consequently, regeneration of
the column results in dissociation of a highly purified CSN complex, together
with its associated proteins. Immunopurification of the CSN from various human
tissues or experimental conditions is advantageous for the generation of numerous
CSN-interaction maps.
PMID- 27613031
TI - Studying Protein Ubiquitylation in Yeast.
AB - Ubiquitylation is a reversible posttranslational modification that is critical
for most, if not all, cellular processes and essential for viability. Ubiquitin
conjugates to substrate proteins either as a single moiety (monoubiquitylation)
or as polymers composed of ubiquitin molecules linked to each other with various
topologies and structures (polyubiquitylation). This contributes to an elaborate
ubiquitin code that is decrypted by specific ubiquitin-binding proteins. Indeed,
these different types of ubiquitylation have different functional outcomes,
notably affecting the stability of the substrate, its interactions, its activity,
or its subcellular localization. In this chapter, we describe protocols to
determine whether a protein is ubiquitylated, to identify the site that is
ubiquitylated, and provide direction to study the topology of the ubiquitin
modification, in the yeast Saccharomyces cerevisiae.
PMID- 27613032
TI - Strategies to Detect Endogenous Ubiquitination of a Target Mammalian Protein.
AB - Different biochemical techniques are well established to investigate target's
ubiquitination in mammals without overexpressing a tagged version of ubiquitin
(Ub). The simplest and more direct approach is to immunoprecipitate (IP) your
target protein from cell lysate (stimulated and/or properly treated), followed by
western blot analysis utilizing specific antibodies against Ub (see Subheading
3.1). This approach requires a good antibody against the target working in IP;
alternatively, one could express a tagged version of the protein, possibly at the
endogenous level. Another approach consists in IP ubiquitinated proteins from
total cell lysate followed by detection with the antibody against the protein of
interest. This second method relies on the availability of specific and very
efficient antibodies against Ub (see Subheading 3.2). A more quantitative
approach is the DELFIA assay (Perkin Elmer), an ELISA-based assay, which allows
comparing more samples and conditions (see Subheading 3.3). Cross-validation with
more than one approach is usually recommended in order to prove that your protein
is modified by ubiquitin.Here we will use the EGFR as model system but protocols
can be easily modified according to the protein of interest.
PMID- 27613033
TI - In Vitro Ubiquitination: Self-Ubiquitination, Chain Formation, and Substrate
Ubiquitination Assays.
AB - Ubiquitination of proteins in vitro has evolved as an indispensable tool for the
functional analysis of this posttranslational modification. In vitro
ubiquitination is particularly helpful to study conjugation mechanisms. The
efficiency of the ubiquitination reaction depends in part on the quality of the
enzymes utilized. Here we introduce the assay developed in our lab to study HECT
E3 ligases. It involves bacterially expressed E1, His-tagged Ube2D3 (also called
UbcH5c, the best E2 for Nedd4), untagged Nedd4, and untagged ubiquitin (Ub). As
tags may impair specific activity of the enzymes or even interfere with the
enzymatic reaction, they should be avoided, removed, or kept to a minimal size
whenever possible, unless proven to be without consequence. The protocol
described here is suitable for other E3 ligases capable of forming Ub chains as
pseudo-product of the enzyme reaction. It is also adapted to include substrates.
In this case, substrates should be tagged and purified after the reaction is
completed to allow the detection of the ubiquitinated products.
PMID- 27613034
TI - Isolation of the Ubiquitin-Proteome from Tumor Cell Lines and Primary Cells Using
TUBEs.
AB - Tandem ubiquitin-binding entities (TUBEs) act as molecular traps to isolate
polyubiquitylated proteins facilitating the study of this highly reversible
posttranslational modification. We provide here sample preparation and
adaptations required for TUBE-based enrichment of the ubiquitin proteome from
tumor cell lines or primary cells. Our protocol is suitable to identify ubiquitin
substrates, enzymes involved in the ubiquitin proteasome pathway, as well as
proteasome subunits by mass spectrometry. This protocol was adapted to prepare
affinity columns, reduce background, and improve the protein recovery depending
on the sample source and necessities.
PMID- 27613035
TI - TUBEs-Mass Spectrometry for Identification and Analysis of the Ubiquitin
Proteome.
AB - Mass spectrometry (MS) has become the method of choice for the large-scale
analysis of protein ubiquitylation. There exist a number of proposed methods for
mapping ubiquitin sites, each with different pros and cons. We present here a
protocol for the MS analysis of the ubiquitin-proteome captured by TUBEs and
subsequent data analysis. Using dedicated software and algorithms, specific
information on the presence of ubiquitylated peptides can be obtained from the MS
search results. In addition, a quantitative and functional analysis of the
ubiquitylated proteins and their interacting partners helps to unravel the
biological and molecular processes they are involved in.
PMID- 27613036
TI - Isolation of Ubiquitinated Proteins to High Purity from In Vivo Samples.
AB - Ubiquitination pathways are widely used within eukaryotic cells. The complexity
of ubiquitin signaling gives rise to a number of problems in the study of
specific pathways. One problem is that not all processes regulated by ubiquitin
are shared among the different cells of an organism (e.g., neurotransmitter
release is only carried out in neuronal cells). Moreover, these processes are
often highly temporally dynamic. It is essential therefore to use the right
system for each biological question, so that we can characterize pathways
specifically in the tissue or cells of interest. However, low stoichiometry, and
the unstable nature of many ubiquitin conjugates, presents a technical barrier to
studying this modification in vivo. Here, we describe two approaches to isolate
ubiquitinated proteins to high purity. The first one favors isolation of the
whole mixture of ubiquitinated material from a given tissue or cell type,
generating a survey of the ubiquitome landscape for a specific condition. The
second one favors the isolation of just one specific protein, in order to
facilitate the characterization of its ubiquitinated fraction. In both cases,
highly stringent denaturing buffers are used to minimize the presence of
contaminating material in the sample.
PMID- 27613037
TI - Method for the Purification of Endogenous Unanchored Polyubiquitin Chains.
AB - Unanchored polyubiquitin chains are endogenous non-substrate linked ubiquitin
polymers which have emerging roles in the control of cellular physiology. We
describe an affinity purification method based on an isolated ubiquitin-binding
domain, the ZnF_UBP domain of the deubiquitinating enzyme USP5, which permits the
selective purification of mixtures of endogenous unanchored polyubiquitin chains
that are amenable to downstream molecular analyses. Further, we present methods
for detection of unanchored polyubiquitin chains in purified fractions.
PMID- 27613038
TI - Fluorescent Tools for In Vivo Studies on the Ubiquitin-Proteasome System.
AB - The ubiquitin-proteasome system (UPS) plays a key role in maintaining
proteostasis by degrading most of the cellular proteins. Traditionally, UPS
activity is studied in vitro, in yeast, or in mammalian cell cultures by using
short-lived GFP-based UPS reporters. Here, we present protocols for two
fluorescent tools facilitating real-time imaging of UPS activity in living
animals. We have generated transgenic Caenorhabditis elegans (C. elegans)
expressing a photoconvertible UbG76V-Dendra2 UPS reporter, which permits
measurement of reporter degradation by the proteasome independently of reporter
protein synthesis, and a fluorescent polyubiquitin-binding reporter for detection
of the endogenous pool of Lys48-linked polyubiquitinated proteasomal substrates.
These reporter systems facilitate cell- and tissue-specific analysis of UPS
activity especially in young adult animals, but can also be used for studies
during development, aging, and for example stress conditions.
PMID- 27613039
TI - Bimolecular Fluorescence Complementation to Assay the Interactions of
Ubiquitylation Enzymes in Living Yeast Cells.
AB - Ubiquitylation is a versatile posttranslational protein modification catalyzed
through the concerted action of ubiquitin-conjugating enzymes (E2s) and ubiquitin
ligases (E3s). These enzymes form transient complexes with each other and their
modification substrates and determine the nature of the ubiquitin signals
attached to their substrates. One challenge in the field of protein
ubiquitylation is thus to identify the E2-E3 pairs that function in the cell. In
this chapter, we describe the use of bimolecular fluorescence complementation to
assay E2-E3 interactions in living cells, using budding yeast as a model
organism.
PMID- 27613040
TI - Monitoring Ubiquitin-Coated Bacteria via Confocal Microscopy.
AB - Salmonella is a gram-negative facultative intracellular pathogen that is capable
of infecting a variety of hosts. Inside host cells, most Salmonella bacteria
reside and replicate within Salmonella-containing vacuoles. They use virulence
proteins to manipulate the host cell machinery for their own benefit and hijack
the host cytoskeleton to travel toward the perinuclear area. However, a fraction
of bacteria escapes into the cytosol where they get decorated with a dense layer
of polyubiquitin, which labels the bacteria for clearance by autophagy. More
specifically, autophagy receptor proteins recognize the ubiquitinated bacteria
and deliver them to autophagosomes, which subsequently fuse to lysosomes. Here,
we describe methods used to infect HeLa cells with Salmonella bacteria and to
detect their ubiquitination via immunofluorescence and laser scanning confocal
microscopy.
PMID- 27613041
TI - Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular
Ubiquitylation In Vitro and In Vivo.
AB - The anaphase-promoting complex or cyclosome (APC/C) is one of the major
orchestrators of the cell division cycle in mammalian cells. The APC/C acts as a
ubiquitin ligase that triggers sequential ubiquitylation of a significant number
of substrates which will be eventually degraded by proteasomes during major
transitions of the cell cycle. In this chapter, we present accessible
methodologies to assess both in in vitro conditions and in cellular systems
ubiquitylation reactions mediated by the APC/C. In addition, we also describe
techniques to evidence the changes in protein stability provoked by modulation of
the activity of the APC/C. Finally, specific methods to analyze interactors or
posttranslational modifications of particular APC/C subunits are also discussed.
Given the crucial role played by the APC/C in the regulation of the cell cycle,
this review only focuses on its action and effects in actively proliferating
cells.
PMID- 27613042
TI - Detection and Analysis of SUMOylation Substrates In Vitro and In Vivo.
AB - SUMOylation is a widely used protein posttranslational mechanism capable of
regulating substrates localization, stability, and/or activity. Identification
and characterization of bona fide SUMO substrates is a laborious task but its
discovery can shed light to exquisite and crucial regulatory signaling events
occurring within the cell. Experiments performed in the SUMOylation field often
demand a good understanding of the putative substrate's function and necessitate
a solid knowledge regarding both in vitro and in vivo approaches. This
contribution offers a simplified view into some of the most common experiments
performed in biochemical and cell biological research of the SUMO pathway in
mammalian systems. It also summarizes and updates well established protocols and
tricks in order to improve the likelihood to obtain reliable and reproducible
results.
PMID- 27613043
TI - Detection of Protein-Protein Interactions and Posttranslational Modifications
Using the Proximity Ligation Assay: Application to the Study of the SUMO Pathway.
AB - The detection of protein-protein interactions by imaging techniques often
requires the overexpression of the proteins of interest tagged with fluorescent
molecules, which can affect their biological properties and, subsequently, flaw
experiment interpretations. The recent development of the proximity ligation
assays (PLA) technology allows easy visualization of endogenous protein-protein
interactions at the single molecule level. PLA relies on the use of combinations
of antibodies coupled to complementary oligonucleotides that are amplified and
revealed with a fluorescent probe, each spot representing a single protein
protein interaction. Another application of this technique is the detection of
proteins posttranslational modifications to monitor their localization and
dynamics in situ. Here, we describe the use of PLA to detect protein SUMOylation,
a posttranslational modification related to ubiquitination, as well as
interaction of SUMOylated substrates with other proteins, using both adherent and
suspension cells.
PMID- 27613044
TI - Dissecting SUMO Dynamics by Mass Spectrometry.
AB - Protein modification by SUMO proteins is one of the key posttranslational
modifications in eukaryotes. Here, we describe a workflow to analyze SUMO
dynamics in response to different stimuli, purify SUMO conjugates, and analyze
the changes in SUMOylation level in organisms, tissues, or cell culture. We
present a protocol for lysis in denaturing conditions that is compatible with
downstream IMAC and antibody affinity purification, followed by mass spectrometry
and data analysis.
PMID- 27613045
TI - Isolation of Lysosomes from Mammalian Tissues and Cultured Cells.
AB - Lysosomes participate within the cells in the degradation of organelles,
macromolecules, and a wide variety of substrates. In any study on specific roles
of lysosomes, both under physiological and pathological conditions, it is
advisable to include methods that allow their reproducible and reliable
isolation. However, purification of lysosomes is a difficult task, particularly
in the case of cultured cells. This is mainly because of the heterogeneity of
these organelles, along with their low number and high fragility. Also, isolation
methods, while disrupting plasma membranes, have to preserve the integrity of
lysosomes, as the breakdown of their membranes releases enzymes that could damage
all cell organelles, including themselves. The protocols described below have
been routinely used in our laboratory for the specific isolation of lysosomes
from rat liver, NIH/3T3, and other cultured cells, but can be adapted to other
mammalian tissues or cell lines.
PMID- 27613046
TI - Analysis of Relevant Parameters for Autophagic Flux Using HeLa Cells Expressing
EGFP-LC3.
AB - Macroautophagy (called just autophagy hereafter) is an intracellular degradation
machinery essential for cell survival under stress conditions and for the
maintenance of cellular homeostasis. The hallmark of autophagy is the formation
of double membrane vesicles that engulf cytoplasmic material. These vesicles,
called autophagosomes, mature by fusion with endosomes and lysosomes that allows
the degradation of the cargo. Autophagy is a dynamic process regulated at
multiple steps. Assessment of autophagy is not trivial because the number
autophagosomes might not necessarily reflect the real level of autophagic
degradation, the so-called autophagic flux. Here, we describe an optimized
protocol for the analysis of relevant parameters of autophagic flux using HeLa
cells stably expressing EGFP-LC3. These cells are a convenient tool to determine
the influence of the downregulation or overexpression of specific proteins in the
autophagic flux as well as the analysis of autophagy-modulating compounds.
Western blot analysis of relevant parameters, such as the levels of EGFP-LC3,
free EGFP generated by autophagic degradation and endogenous LC3.I-II are
analyzed in the presence and absence of the autophagic inhibitor chloroquine.
PMID- 27613047
TI - Analysis of Protein Oligomeric Species by Sucrose Gradients.
AB - Protein misfolding, aggregation, and accumulation are a common hallmark in
various neurodegenerative diseases. Invariably, the process of protein
aggregation is associated with both a loss of the normal biological function of
the protein and a gain of toxic function that ultimately leads to cell death. The
precise origin of protein cytotoxicity is presently unclear but the predominant
theory posits that smaller oligomeric species are more toxic than larger
aggregated forms. While there is still no consensus on this subject, this is a
central question that needs to be addressed in order to enable the design of
novel and more effective therapeutic strategies. Accordingly, the development and
utilization of approaches that allow the biochemical characterization of the
formed oligomeric species in a given cellular or animal model will enable the
correlation with cytotoxicity and other parameters of interest.Here, we provide a
detailed description of a low-cost protocol for the analysis of protein
oligomeric species from both yeast and mammalian cell lines models, based on
their separation according to sedimentation velocity using high-speed
centrifugation in sucrose gradients. This approach is an adaptation of existing
protocols that enabled us to overcome existing technical issues and obtain
reliable results that are instrumental for the characterization of the types of
protein aggregates formed by different proteins of interest in the context of
neurodegenerative disorders.
PMID- 27613048
TI - Analysis of Protein Oligomerization by Electrophoresis.
AB - A polypeptide chain can interact with other polypeptide chains and form stable
and functional complexes called "oligomers." Frequently, biochemical analysis of
these complexes is made difficult by their great size. Traditionally, size
exclusion chromatography, immunoaffinity chromatography, or immunoprecipitation
techniques have been used to isolate oligomers. Components of these oligomers are
then further separated by sodium dodecyl sulfate polyacrylamide gel
electrophoresis and identified by immunoblotting with specific antibodies.
Although they are sensitive, these techniques are not easy to perform and
reproduce. The use of Tris-acetate polyacrylamide gradient gel electrophoresis
allows the simultaneous analysis of proteins in the mass range of 10-500 kDa. We
have used this characteristic together with cross-linking reagents to analyze the
oligomerization of endogenous proteins with a single electrophoretic gel. We
demonstrate how the oligomerization of p53, the pyruvate kinase isoform M2, or
the heat shock protein 27 can be studied with this system. We also show how this
system is useful for studying the oligomerization of large proteins such as
clathrin heavy chain or the tuberous sclerosis complex. Oligomerization analysis
is dependent on the cross-linker used and its concentration. All of these
features make this system a very helpful tool for the analysis of protein
oligomerization.
PMID- 27613049
TI - Blot-MS of Carbonylated Proteins: A Tool to Identify Oxidized Proteins.
AB - The efficiency of proteostasis regulation declines during aging and the failure
of protein homeostasis is common in age-related diseases. Protein oxidation is a
major contributor to the loss of proteome homeostasis, also called
"proteostasis," precluding protein misfolding and aggregation. So, the
identification of the molecular pathways impaired by protein oxidation will
increase the understanding of proteostasis and the pathophysiological conditions
related to the loss of proteostasis. Sample derivatization with dinitrophenyl
hydrazine and western blot immunoassay detection of carbonylated proteins
(commonly known as OxyblotTM) coupled to mass spectrometry (blot-MS) is an
attractive methodological approach to identify proteins that are more prone to
carbonylation, a typical oxidative modification of amino acid residues. The
integration of blot-MS data of carbonylated proteins with bioinformatics tools
allows the identification of the biological processes more affected by protein
oxidation and that, eventually, result in the loss of proteostasis.In this
chapter, we describe a blot-MS methodology to identify the proteins more prone to
oxidation in biological samples, as cell and tissue extracts, and biofluids.
Analysis of mitochondria isolated from cardiac tissue is provided as an example.
Bioinformatic strategy to deal with data retrieved from blot-MS experiments are
proposed for the identification of relevant biological processes modulated by
oxidative stress stimuli.
PMID- 27613050
TI - Quantitation of Protein Translation Rate In Vivo with Bioorthogonal Click
Chemistry.
AB - The development of novel bioorthogonal reactives that can be used to tag
biomolecules in vivo has revolutionized the studies of cellular and molecular
biology. Among those novel reactive substances, amino acid analogs can be used to
label nascent proteins, thus opening new avenues for measuring protein
translation rates in vivo with a limited manipulation of the sample. Here, we
describe the use of Click-chemistry to tag and separate newly synthesized
proteins in mammalian cells that can be used, coupled with western analysis, to
estimate the translation rate of any protein of interest.
PMID- 27613051
TI - A Simple Protocol for High Efficiency Protein Isolation After RNA Isolation from
Mouse Thyroid and Other Very Small Tissue Samples.
AB - As a dedicated hormone-secreting organ, the thyroid gland possesses a complement
of proteostatic systems, including antioxidant, unfolded protein, and autophagic
responses. The vast majority of animal investigations of thyroid physiology and,
more recently, proteostasis, have utilized as model the rat, rather than the
mouse. This is due to the very small size of the thyroid gland in the latter,
with a total weight of ~2 mg (~1 mg per thyroid lobe). However, this strategy has
limited the utilization of genetic approaches, such as taking advantage of the
various transgenic and knockout mouse models. Here, we describe a simple and
highly efficient protocol for the simultaneous isolation of mRNA, micro-RNA and
150-200 MUg of protein from as little as 1 mg of mouse thyroid tissue, the
average weight of one of the two thyroid lobes, thus preserving the other lobe
for immunohistochemical or other analyses. While our workflow is similar to other
protocols published in the literature and/or proposed by commercial reagent
providers, we have introduced a key modification that addresses efficiently the
most challenging step of the protein isolation process: the solubilization of the
protein pellet after RNA extraction and protein precipitation. We demonstrate the
feasibility of our approach and its utility for downstream analyses (including
Western blotting) that facilitate the comparative study of proteostatic pathways
in the mouse thyroid. We have also successfully applied this protocol on samples
from mouse liver, brown and white adipose tissue, as well as from rodent cell
lines.
PMID- 27613052
TI - Monitoring Target Engagement of Deubiquitylating Enzymes Using Activity Probes:
Past, Present, and Future.
AB - Deubiquitylating enzymes or DUBs are a class of enzymes that selectively remove
the polypeptide posttranslational modification ubiquitin from a number of
substrates. Approximately 100 DUBs exist in human cells and are involved in key
regulatory cellular processes, which drive many disease states, making them
attractive therapeutic targets. Several aspects of DUB biology have been studied
through genetic knock-out or knock-down, genomic, or proteomic studies. However,
investigation of enzyme activation and regulation requires additional tools to
monitor cellular and physiological dynamics. A comparison between genetic
ablation and dominant-negative target validation with pharmacological inhibition
often leads to striking discrepancies. Activity probes have been used to profile
classes of enzymes, including DUBs, and allow functional and dynamic properties
to be assigned to individual proteins. The ability to directly monitor DUB
activity within a native biological system is essential for understanding the
physiological and pathological role of individual DUBs. We will discuss the
evolution of DUB activity probes, from in vitro assay development to their use in
monitoring DUB activity in cells and in animal tissues, as well as recent
progress and prospects for assessing DUB inhibition in vivo.
PMID- 27613053
TI - Activity Based Profiling of Deubiquitylating Enzymes and Inhibitors in Animal
Tissues.
AB - The attachment of ubiquitin or ubiquitin-like modifiers to proteins is an
important signal for the regulation of a variety of biological processes
including the targeting of substrates for degradation, receptor internalization,
regulation of gene expression, and DNA repair. Posttranslational modification of
proteins by ubiquitin controls many cellular processes, and aberrant
ubiquitylation can contribute to cancer, immunopathologies, and
neurodegeneration. Thus, deubiquitylating enzymes (DUBs) that remove ubiquitin
from proteins have become attractive therapeutic targets. Monitoring the activity
of DUBs in cells or in tissues is critical for understanding the biological
function of DUBs in particular pathways and is essential for determining the
physiological specificity and potency of small-molecule DUB inhibitors. Here, we
describe a method for the homogenization of animal tissues and incubation of
tissue lysates with ubiquitin-based activity probes to monitor DUB activity in
mouse tissues and target engagement following treatment of animals with small
molecule DUB inhibitors.
PMID- 27613054
TI - High-Throughput siRNA Screening Applied to the Ubiquitin-Proteasome System.
AB - The ubiquitin-proteasome system is the major pathway for intracellular protein
degradation in eukaryotic cells. Due to the large number of genes dedicated to
the ubiquitin-proteasome system, mapping degradation pathways for short lived
proteins is a daunting task, in particular in mammalian cells that are not
genetically tractable as, for instance, a yeast model system. Here, we describe a
method relying on high-throughput cellular imaging of cells transfected with a
targeted siRNA library to screen for components involved in degradation of a
protein of interest. This method is a rapid and cost-effective tool which is also
highly applicable for other studies on gene function.
PMID- 27613055
TI - High-Throughput Yeast-Based Reporter Assay to Identify Compounds with Anti
inflammatory Potential.
AB - The association between altered proteostasis and inflammatory responses has been
increasingly recognized, therefore the identification and characterization of
novel compounds with anti-inflammatory potential will certainly have a great
impact in the therapeutics of protein-misfolding diseases such as degenerative
disorders. Although cell-based screens are powerful approaches to identify
potential therapeutic compounds, establishing robust inflammation models amenable
to high-throughput screening remains a challenge. To bridge this gap, we have
exploited the use of yeasts as a platform to identify lead compounds with anti
inflammatory properties. The yeast cell model described here relies on the high
degree homology between mammalian and yeast Ca(2+)/calcineurin pathways
converging into the activation of NFAT and Crz1 orthologous proteins,
respectively. It consists of a recombinant yeast strain encoding the lacZ gene
under the control of Crz1-recongition elements to facilitate the identification
of compounds interfering with Crz1 activation through the easy monitoring of beta
galactosidase activity. Here, we describe in detail a protocol optimized for high
throughput screening of compounds with potential anti-inflammatory activity as
well as a protocol to validate the positive hits using an alternative beta
galactosidase substrate.
PMID- 27613057
TI - Global MS-Based Proteomics Drug Profiling.
AB - DNA-based technologies such as RNAi, chemical-genetic profiling, or gene
expression profiling by DNA microarrays combined with other biochemical methods
are established strategies for surveying drug mechanisms. Such approaches can
provide mechanistic information on how drugs act and affect cellular pathways. By
studying how cancer cells compensate for the drug treatment, novel targets used
in a combined treatment can be designed. Furthermore, toxicity effects on cells
not targeted can be obtained on a molecular level. For example, drug companies
are particularly interested in studying the molecular side effects of drugs in
the liver. In addition, experiments with the purpose of elucidating liver
toxicity can be studied using samples obtained from animal models exposed to
different concentrations of a drug over time. More recently considerable advances
in mass spectrometry (MS) technologies and bioinformatics tools allows
informative global drug profiling experiments to be performed at a cost
comparable to other large-scale technologies such as DNA-based technologies.
Moreover, MS-based proteomics provides an additional layer of information on the
dynamic regulation of proteins translation and particularly protein degradation.
MS-based proteomics approaches combined with other biochemical methods delivers
information on regulatory networks, signaling cascades, and metabolic pathways
upon drug treatment. Furthermore, MS-based proteomics can provide additional
information on single amino acid polymorphisms, protein isoform distribution,
posttranslational modifications, and subcellular localization. In this chapter,
we will share our experience using MS based proteomics as a pharmacoproteomics
strategy to characterize drug mechanisms of action in single drug therapy or in
multidrug combination. Finally, the emergence of integrated proteogenomics
analysis, such as "The Cancer Genome Atlas" program, opened interesting
perspectives to extend this approach to drug target discovery and validation.
PMID- 27613056
TI - Using AlphaScreen((r)) to Identify Small-Molecule Inhibitors Targeting a
Conserved Host-Pathogen Interaction.
AB - AlphaScreen((r)) is a technology particularly suitable for bi-molecular inhibitor
screening assays, e.g. using protein-protein interactions with purified
recombinant proteins. Each binding partner of the bi-molecular interaction is
coupled either to donor or to acceptor beads. The technology is based on the
quantifiable transfer of oxygen singlets from donor to acceptor microbeads
brought together by a specific interaction between the partners. We identified
the conserved interaction between WW domains of cellular ubiquitin ligases of the
Nedd4 family and a short peptide motif (PPxY) present in several structural and
non-structural viral proteins as a potential drug target. Using an AlphaScreen
assay recapitulating the interaction between Nedd4.2 and the PPxY motif of the
adenoviral capsid protein VI, we screened a library of small molecules and
identified specific inhibitors of this interaction.
PMID- 27613058
TI - Finding a Sense of Home across the Pacific in Old Age- Chinese American Senior's
Report of Life Satisfaction in a Foreign Land.
AB - Finding a sense of home for international migrants is challenging. It is even
more so for older adults who migrate to a foreign country later in life to follow
their adult children. This study examines Chinese immigrant elders' report of
their sense of home and life-satisfaction. Based on 21 intensive interviews
and107 surveys with elderly immigrants of Chinese descent, this research finds
that a comfortable living condition in a natural and built environment contribute
to Chinese elders' narrative of a sense of home. The lack of English language,
however, makes immigrant Chinese elders feel very unsettled. Being together with
children and having good social benefits are major pull factors that contribute
to immigrant elders' decision to settle down in a foreign country. Those who
report a stronger sense of home tend to report a higher level of life
satisfaction. In conclusion, the authors argue that immigrant elders are defining
their sense of home with a greater sense of independence from their adult
children. Favorable social policies toward older adults, such as Medicare,
Medicaid, low income housing, and social services, are important factors that
make older immigrants feel a sense of home in a foreign land, although the
inability to communicate is a barrier to a complete sense of home for
transnational migrants in old age.
PMID- 27613059
TI - An association between newly diagnosed cutaneous T cell lymphoma and prior
impetigo: a nested case-control study.
AB - Colonization with staphylococcus aureus (SA) is associated with disease activity
and progression in patients with cutaneous T-cell lymphoma (CTCL) secondary to T
cell activation by bacterial superantigens. The aim of the current study was to
evaluate the possible role of SA as an etiologic factor affecting CTCL
initiation. We conducted a nested case-control study in a large population
representative database from the UK. Cases were defined as all patients with an
incident diagnosis of mycosis fungoides (MF) or Sezary syndrome (SS) between 1995
and 2013. For every case, four eligible controls matched on age, sex, practice
site, and duration of follow-up were selected. Exposure of interest was clinical
diagnosis of impetigo prior to CTCL diagnosis. Conditional logistic regression
was used to calculate odds-ratio (ORs) and 95 % confidence-interval (CI) for CTCL
risk. The results were further stratified according to age, sex and time interval
between impetigo and CTCL diagnosis. The study population included 310 cases with
MF or SS and 1223 matched controls. Among cases with CTCL 4.8 % (n = 15) had
impetigo prior to cancer diagnosis compared to 2 % (n = 24) of controls. The
adjusted OR for CTCL diagnosis among patients with prior impetigo was 2.33 (95 %
CI 1.12-4.83). The risk was elevated among individuals with impetigo 1-5 years
before cancer diagnosis (OR 3.33, 95 % CI 1.00-11.10). There was no change in
risk among patients with impetigo more than 5 years before cancer diagnosis (OR
1.09, 95 % CI 0.35-3.37). Our results suggest a possible association between SA
colonization and CTCL initiation that might serve as an important etiological
factor for the disease.
PMID- 27613060
TI - Aberrant splicing and drug resistance in AML.
AB - The advent of next-generation sequencing technologies has unveiled a new window
into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent
mutations in spliceosome machinery and genome-wide aberrant splicing events have
been recognized as a prominent component of this disease. This review will focus
on how these factors influence drug resistance through altered splicing of tumor
suppressor and oncogenes and dysregulation of the apoptotic signaling network. A
better understanding of these factors in disease progression is necessary to
design appropriate therapeutic strategies recognizing specific alternatively
spliced or mutated oncogenic targets.
PMID- 27613062
TI - Re: Focal Laser Ablation of Prostate Cancer: Phase I Clinical Trial.
PMID- 27613061
TI - Partial Prostatectomy for Anterior Cancer: Short-term Oncologic and Functional
Outcomes.
AB - BACKGROUND: Focal ablative therapy may be a suboptimal option for anterior
prostate cancers (APCs) reaching the prostate apex due to concerns for thermal
injury to the external sphincter. OBJECTIVE: To explore the technical feasibility
of anterior partial prostatectomy (APP) for isolated APCs detected by magnetic
resonance imaging (MRI), and to report short-term oncologic and functional
outcomes. DESIGN, SETTING, AND PARTICIPANTS: Following institutional review board
approval, over an 8-yr period (2008-2015) 17 consenting patients were enrolled in
a prospective single-arm single-center Innovation, Development, Exploration,
Assessment, Long-term (IDEAL) phase 2a study. Inclusion criteria comprised
preurethral, low- to intermediate-risk APC diagnosed by MRI, and targeted
biopsies. Robotic template APP was performed; posterolateral aspect of the
submontanal urethra, peripheral zone, and periprostatic tissues were preserved
intact. Median follow-up was 30 mo (interquartile range [IQR]: 25-70). OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: We noted the incidence of perioperative
complications and examined reports of pathology, prostate-specific antigen (PSA),
imaging, biopsies, and questionnaires. RESULTS AND LIMITATIONS: Preoperatively,
median PSA was 9.8 ng/ml, Gleason score was 6-7 (3 + 4), and cancer volume was
3.7cm3 (IQR: 1.7-4.6). The technique was feasible in all cases. Perioperative
complications included anastomotic leak (12%; G2), urinary tract infection (6%;
G2), and transient intestinal ileus in one case (6%; G2). At 3 mo, continence and
potency rates were 100% and 83%, respectively. Median nadir PSA was 0.4 ng/ml
(IQR: 0.3-0.7). All margins and posterolateral margins rates were 55% and 35%,
respectively. APC recurrence-free survival at 2 yr was 0.86 (95% confidence
interval [CI], 0.55-0.96). Four patients (24%) who recurred underwent an
uncomplicated completion of robot-assisted prostatectomy. Regarding limitations,
CIs are quite wide for reported outcomes. CONCLUSIONS: Robotic partial
prostatectomy for isolated APC is feasible with good functional results. While
promising, much more research is needed to verify our initial outcomes and
appropriately position APP in the treatment paradigms for APC. PATIENT SUMMARY:
We explored a novel approach for partial prostatic surgical ablation for prostate
cancer located in the anterior part of the prostate as an alternative to other
focal ablative techniques.
PMID- 27613064
TI - Follow the LEADER-Liraglutide Effect and Action in Diabetes: Evaluation of
Cardiovascular Outcome Results Trial.
AB - This commentary analyzes the Liraglutide Effect and Action in Diabetes:
Evaluation of Cardiovascular Outcome Results (LEADER) trial, which has reported
the cardiovascular benefits of liraglutide. It places the results of this seminal
trial in the context of the evolution of diabetes care, compares them with other
recently published cardiovascular outcome trials, and suggests novel mechanisms
to explain the benefits and properties of liraglutide. The editorial discusses
the potential impact that LEADER will have on the prevention and management of
diabetes and its vascular complications.
PMID- 27613068
TI - Synthesis of Fe and N Co-doped Bi2Ti2O7 Nanofiber with Enhanced Photocatalytic
Activity Under Visible Light Irradiation.
AB - A series of N-Fe-Bi2Ti2O7 nanofibers were successfully synthesized. The
structure, morphology, visible light photocatalytic properties, and the
degradation mechanism of N-Fe-Bi2Ti2O7 were investigated. A new phase of Bi4Ti3O7
and smaller band gap could be observed after doing Fe and N into Bi2Ti2O7. It can
degrade 66 % MO and 87 % MB in 120 min under visible light irradiation, which is
much more than that of pure Bi2Ti2O7. The results indicate that such unique
structure could enhance the charge transfer between the nanostructure interfaces
and therefore improve its photocatalytic activities.
PMID- 27613067
TI - Size Control and Growth Process Study of Au@Cu2O Particles.
AB - Au@Cu2O cuboctahedron with gold triangular nanoplate core and Cu2O shell was
synthesized by a chemical method. X-ray diffraction (XRD) and transmission
electron microscopy (TEM) tests demonstrated that the as-synthesis samples were
consisted of gold triangular nanoplate core and Cu2O shell, and both of them were
in good crystallization. The effective size control of the particles could be
realized by controlling the amount of Au cores added in the synthetic process and
Au@Cu2O particles with different shell thickness could be synthesized. The
decrease of Cu2O shell thickness had a great difference in the optical
performance, including blue shift of the resonant peaks and enhanced absorption
intensity. The growth process from rough sheet structure to cuboctahedron was
also explored. The results of photocatalytic degradation experiment showed that
Au@Cu2O particles showed much better photocatalytic performance than that of pure
Cu2O. The improved photocatalytic property of the Au@Cu2O particles was
attributed to the comprehensive effect of the enhanced visible-light absorption
and high separation rate of electron-hole pairs.
PMID- 27613063
TI - Structure-function analysis of Avian beta-defensin-6 and beta-defensin-12: role
of charge and disulfide bridges.
AB - BACKGROUND: Avian beta-defensins (AvBD) are small, cationic, antimicrobial
peptides. The potential application of AvBDs as alternatives to antibiotics has
been the subject of interest. However, the mechanisms of action remain to be
fully understood. The present study characterized the structure-function
relationship of AvBD-6 and AvBD-12, two peptides with different net positive
charges, similar hydrophobicity and distinct tissue expression profiles. RESULTS:
AvBD-6 was more potent than AvBD-12 against E. coli, S. Typhimurium, and S.
aureus as well as clinical isolates of extended spectrum beta lactamase (ESBL)
positive E. coli and K. pneumoniae. AvBD-6 was more effective than AvBD-12 in
neutralizing LPS and interacting with bacterial genomic DNA. Increasing bacterial
concentration from 10(5) CFU/ml to 10(9) CFU/ml abolished AvBDs' antimicrobial
activity. Increasing NaCl concentration significantly inhibited AvBDs'
antimicrobial activity, but not the LPS-neutralizing function. Both AvBDs were
mildly chemotactic for chicken macrophages and strongly chemotactic for CHO-K1
cells expressing chicken chemokine receptor 2 (CCR2). AvBD-12 at higher
concentrations also induced chemotactic migration of murine immature dendritic
cells (DCs). Disruption of disulfide bridges abolished AvBDs' chemotactic
activity. Neither AvBDs was toxic to CHO-K1, macrophages, or DCs. CONCLUSIONS:
AvBDs are potent antimicrobial peptides under low-salt conditions, effective LPS
neutralizing agents, and broad-spectrum chemoattractant peptides. Their
antimicrobial activity is positively correlated with the peptides' net positive
charges, inversely correlated with NaCl concentration and bacterial
concentration, and minimally dependent on intramolecular disulfide bridges. In
contrast, their chemotactic property requires the presence of intramolecular
disulfide bridges. Data from the present study provide a theoretical basis for
the design of AvBD-based therapeutic and immunomodulatory agents.
PMID- 27613069
TI - Normal Incident Long Wave Infrared Quantum Dash Quantum Cascade Photodetector.
AB - We demonstrate a quantum dash quantum cascade photodetector (QDash-QCD) by
incorporating self-assembled InAs quantum dashes into the active region of a long
wave infrared QCD. Sensitive photoresponse to normal incident light at 10 MUm was
observed, which is attributed to the intersubband (ISB) transitions in the
quantum well/quantum dash (QW/QDash) hybrid absorption region and the following
transfer of excited electrons on the extraction stair-like quantum levels
separated by LO-phonon energy. The high density InAs quantum dashes were formed
in the Stranski-Krastanow mode and stair-like levels were formed by a lattice
matched InGaAs/InAlAs superlattice. A stable responsivity from 5 mA/W at 77 K to
3 mA/W at as high as 190 K was observed, which makes the QDash-QCD promising in
high temperature operation.
PMID- 27613070
TI - Flexible Field Emitter for X-ray Generation by Implanting CNTs into Nickel Foil.
AB - This paper reports on a flexible Ni micro wire with CNTs embedded into its
surface. By using micromachining technology, for the first time, we could implant
nanoscale materials into micro-scale metal substrate at room temperature. Thanks
to the effective direct contact and the strong interactions between CNTs and the
substrate, field emission current of 1.11 mA (current density of 22.2 mA/cm(2))
could be achieved from the micro wire. Moreover, the wire shows excellent
mechanical properties for large amplitude bending, which is beneficial for
geometric designing. To check the practical application of the wire, a simplified
X-ray imaging system was set up by modifying a conventional tube. The gray shade
that appears on the sensitive film after being exposed to the radiation confirms
the X-ray generation.
PMID- 27613071
TI - Lack of clinically useful response predictors for treating aggression and
agitation in Alzheimer's disease with citalopram.
PMID- 27613072
TI - Association of vaccine handling conditions with effectiveness of live attenuated
influenza vaccine against H1N1pdm09 viruses in the United States.
AB - PURPOSE: This analysis examined potential causes of the lack of vaccine
effectiveness (VE) of live attenuated influenza vaccine (LAIV) against
A/H1N1pdm09 viruses in the United States (US) during the 2013-2014 season.
Laboratory studies have demonstrated reduced thermal stability of
A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through
2013-2014. METHODS: Post hoc analyses of a 2013-2014 test-negative case-control
(TNCC) effectiveness study investigated associations between vaccine shipping
conditions and LAIV lot effectiveness. Investigational sites provided the LAIV
lot numbers administered to each LAIV recipient enrolled in the study, and the
vaccine distributor used by the site for commercially purchased vaccine.
Additionally, a review was conducted of 2009-2014 pediatric observational TNCC
effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season,
and geographic location. RESULTS: From the 2013 to 2014 TNCC study, the
proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly
higher among children who received a lot released between August 1 and September
15, 2013, compared with a lot shipped either earlier or later (21% versus 4%;
P<0.01). A linear relationship was observed between the proportion of subjects
testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at
distributors' central locations. The review of LAIV VE studies showed that in the
2010-2011 and 2013-2014 influenza seasons, no significant effectiveness of LAIV
against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations
of LAIV in the US, respectively, in contrast to significant effectiveness against
A/H3N2 and B strains during 2010-2014. CONCLUSIONS: This study showed that the
lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated
with exposure of some LAIV lots to temperatures above recommended storage
conditions during US distribution, and is likely explained by the increased
susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal
degradation. CLINICAL TRIAL REGISTRY: NCT01997450.
PMID- 27613074
TI - Spinal fusion surgery: From relief to insecurity.
AB - BACKGROUND: During their decision-making process patients perceive surgery as a
voluntary yet necessary choice. Surgery initiates hope for a life with less pain
but also creates a feeling of existential insecurity in terms of fear, isolation
and uncertainty. AIM: The aim of this study was to explore how patients
experience their situation from the point of making the decision to undergo
spinal fusion surgery to living their everyday life after surgery. METHOD: A
phenomenological-hermeneutic study design was applied based on the French
philosopher Paul Ricoeur's theory of interpretation. Data were collected through
observations and semi-structured interviews. FINDINGS: The recommendation and
decision to undergo spinal fusion surgery felt like a turning point for the
patients and brought hope of regaining their normal lives, of being a more
resourceful parent, partner, friend and colleague with no or less pain. Thus,
deciding to undergo surgery created a brief feeling of relief. However, life with
back pain had changed the patients' understanding of themselves. Consequently,
some patients postoperatively experienced insecurity and a weakened self-image
with difficulties creating meaning in their lives. CONCLUSION: Being recommended
and undergoing spinal fusion surgery initiates hope for a life with less pain and
altered life conditions. At the same time, paradoxically, this creates a feeling
of existential insecurity in terms of facing the surgery and the future to come.
It is, therefore, important to recognise and include the patients' everyday life
experiences concerning how they give (or may not give) meaning to their illness,
i.e. their understanding of how it is affecting them. These aspects are essential
for the patients' definition and re-definition of themselves and thus crucial to
draw upon in the relationship and communication between patient and healthcare
professional.
PMID- 27613073
TI - "Classical organic acidurias": diagnosis and pathogenesis.
AB - Organic acidurias are inherited metabolic diseases due to the deficiency of an
enzyme or a transport protein involved in one of the several cellular metabolic
pathways devoted to the catabolism of amino acids, carbohydrates or lipids. These
deficiencies result in abnormal accumulation of organic acids in the body and
their abnormal excretion in urine. More than 65 organic acidurias have been
described; the incidence varies, individually, from 1 out of 10,000 to >1 out of
1000,000 live births. Collectively, their incidence approximates 1 out of 3000
live births. Among these disorders, methyl malonic aciduria, propionic aciduria,
maple syrup urine disease and isovaleric aciduria are sometimes referred to as
classical organic acidurias. In this review, we focused on the basic GC-MS-based
methodologies employed in the diagnosis of classical organic acidurias and
provided updated reference values for the most common involved organic acids. We
also attempted to provide the most recent updates on the pathogenetic bases of
these diseases.
PMID- 27613075
TI - Cultural Effects on Cancer Prevention Behaviors: Fatalistic Cancer Beliefs and
Risk Optimism Among Asians in Singapore.
AB - Although culture is acknowledged as an important factor that influences health,
little is known about cultural differences pertaining to cancer-related beliefs
and prevention behaviors. This study examines two culturally influenced beliefs
fatalistic beliefs about cancer prevention, and optimistic beliefs about cancer
risk-to identify reasons for cultural disparity in the engagement of cancer
prevention behaviors. We utilized data from national surveys of European
Americans in the United States (Health Information National Trends Survey 4,
Cycle3; N = 1,139) and Asians in Singapore (N = 1,200) to make cultural
comparisons. The odds of an Asian adhering to prevention recommendations were
less than half the odds of a European American, with the exception of smoking
avoidance. Compared to European Americans, Asians were more optimistic about
their cancer risk both in an absolute and a comparative sense, and held stronger
fatalistic beliefs about cancer prevention. Mediation analyses revealed that
fatalistic beliefs and absolute risk optimism among Asians partially explain
their lower engagement in prevention behaviors, whereas comparative risk optimism
increases their likelihood of adhering to prevention behaviors. Our findings
underscore the need for developing culturally targeted interventions in
communicating cancer causes and prevention.
PMID- 27613076
TI - A Randomized Trial Comparing the Pharmacokinetics, Safety, and Tolerability of
DFN-02, an Intranasal Sumatriptan Spray Containing a Permeation Enhancer, With
Intranasal and Subcutaneous Sumatriptan in Healthy Adults.
AB - OBJECTIVE/BACKGROUND: Intranasal sumatriptan (Imitrex(r) ) may be an alternative
for patients who refuse injections and cannot tolerate oral agents, but due to
low bioavailability and slow absorption, the clinical utility of the currently
marketed formulation is limited, highlighting an unmet need for an effective non
oral migraine medication with a rapid onset of action. To overcome the slow
absorption profile associated with intranasal administration, we evaluated the
impact of 1-O-n-Dodecyl-beta-D-Maltopyranoside (DDM, Intravail A-3TM), a
permeation enhancer, on sumatriptan's pharmacokinetic profile by comparing the
pharmacokinetic characteristics of two commercial sumatriptan products, 4 mg
subcutaneous and 6 mg subcutaneous in healthy adults, with DFN-02 - a novel
intranasal agent comprised of sumatriptan 10 mg plus 0.20% DDM. We also
determined the pharmacokinetic characteristics of DDM and evaluated its safety
and tolerability. METHODS: We conducted two studies: a randomized, three-way
crossover study comparing monodose and multidose devices for delivery of single
doses of DFN-02 with commercially available intranasal sumatriptan 20 mg in 18
healthy, fasted adults, and an open-label, randomized, single-dose, three-way
crossover bioavailability study comparing DFN-02 with 4 mg and 6 mg subcutaneous
sumatriptan in 78 healthy, fasted adults. In the study comparing DFN-02 with IN
sumatriptan, subjects received a single dose of DFN-02 (sumatriptan 10 mg plus
DDM 0.20%) via monodose and multidose delivery systems with at least 5 days
between treatments. In the comparison with SC sumatriptan, subjects received a
single dose of each treatment with at least 3 days between treatments. In both
studies, blood was sampled for pharmacokinetic evaluation of sumatriptan and DDM
through 24 hours post-dose; safety and tolerability were monitored throughout.
RESULTS: In the comparison with commercially available intranasal sumatriptan 20
mg, DFN-02 had a more rapid absorption profile; tmax was 15 minutes for DFN-02
monodose, 10.2 minutes for DFN-02 multidose, and 2.0 hours for commercially
available intranasal sumatriptan 20 mg. Compared with 4 and 6 mg subcutaneous
sumatriptan, DFN-02's median tmax (10 minutes) was significantly earlier (15
minutes; P < .0001). Mean sumatriptan exposure metrics were similar for DFN-02
and 4 mg sumatriptan: AUC0-2 : 35.12 and 44.82 ng*hour/mL, respectively; AUC0
infinity : 60.70 and 69.21 ng*hour/mL, respectively; Cmax : 51.79 and 49.07
ng/mL, respectively. With 6 mg subcutaneous sumatriptan, these exposure metrics
were about 50% larger (AUC0-2 : 67.17 ng*hour/mL; AUC0-infinity : 103.78
ng*hour/mL; Cmax : 72.75 ng/mL). Inter-subject variability of AUC0-2 , AUC0
infinity , and Cmax was 42-58% for DFN-02, 15-22% for 4 mg subcutaneous
sumatriptan, and 15-25% for 6 mg subcutaneous sumatriptan. DDM exposure was low
(mean Cmax : 1.63 ng/mL), tmax was 30 minutes, and it was undetectable by 4
hours. There were no serious adverse events, discontinuations due to adverse
events, or remarkable findings for vital signs, physical examinations (including
nasal and injection site examinations), or clinical laboratory assessments. The
overall incidence of adverse events was comparable across treatments, and all
treatment-related events were mild in severity. Adverse events occurring in >=10%
of subjects were dysgeusia (19%), headache (18%), nausea (15%), paresthesia
(15%), and dizziness (12%). CONCLUSIONS: In healthy subjects, DFN-02, an
intranasal spray containing 10 mg sumatriptan plus DDM, had a more rapid
absorption profile than commercially available intranasal sumatriptan 20 mg, and
systemic exposure from a single-dose administration of DFN-02 was similar to 4 mg
SC sumatriptan and two-thirds that of 6 mg SC sumatriptan. With DFN-02, plasma
sumatriptan peaked 5 minutes earlier than with both subcutaneous formulations.
Systemic exposure to sumatriptan was similar with DFN-02 and 4 mg subcutaneous
sumatriptan; both yielded lower systemic exposure than 6 mg subcutaneous
sumatriptan. Systemic exposure to DFN-02's excipient DDM was short-lived. DFN
02's safety and tolerability appear to be comparable to subcutaneous sumatriptan.
Addition of a permeation enhancer improved the absorption profile compared with
commercially available intranasal sumatriptan 20 mg.
PMID- 27613077
TI - New guidelines for management of febrile seizures in Japan.
AB - In 2015, the Japanese Society of Child Neurology released new guidelines for the
management of febrile seizures, the first update of such guidelines since 1996.
In 1988, the Conference on Febrile Convulsions in Japan published "Guidelines for
the Treatment of Febrile Seizures." The Task Committee of the Conference proposed
a revised version of the guidelines in 1996; that version released in 1996 was
used for the next 19years in Japan for the clinical management of children with
febrile seizures. Although the guidelines were very helpful for many clinicians,
new guidelines were needed to reflect changes in public health and the
dissemination of new medical evidence. The Japanese Society of Child Neurology
formed a working group in 2012, and published the new guidelines in March 2015.
The guidelines include emergency care, application of electroencephalography,
neuroimaging, prophylactic diazepam, antipyretics, drugs needing special
attention, and vaccines. While the new guidelines contain updated clinical
recommendations, many unsolved questions remain. These questions should be
clarified by future clinical research.
PMID- 27613078
TI - Effect of corticosterone on larval growth, antipredator behaviour and
metamorphosis of Hylarana indica.
AB - Corticosterone (CORT), a principal glucocorticoid in amphibians, is known to
regulate diverse physiological processes including growth and metamorphosis of
anuran tadpoles. Environmental stressors activate the neuroendocrine stress axis
(hypothalamus-pituitary-interrenal axis, HPI) leading to an acute increase in
CORT, which in turn, helps in coping with particular stress. However, chronic
increase in CORT can negatively affect other physiological processes such as
growth and metamorphosis. Herein, we studied the effect of exogenous CORT on
larval growth, antipredator behaviour and metamorphic traits of Hylarana indica.
Embryonic exposure to 5 or 20MUg/L CORT did not affect their development,
hatching duration as well as larval growth and metamorphosis. Exposure of
tadpoles to 10 or 20MUg/L CORT throughout larval development caused slower growth
and development leading to increased body mass at stage 37. However, body and
tail morphology of tadpoles was not affected. Interestingly, larval exposure to
5, 10 or 20MUg/L CORT enhanced their antipredator response against kairomones in
a concentration-dependent manner. Further, larval exposure to increasing
concentrations of CORT resulted in the emergence of heavier froglets at 10 and
20MUg/L while, delaying metamorphosis at all concentrations. Interestingly, the
heavier froglets had shorter hindlimbs and consequently shorter jump distances.
Tadpoles exposed to 20MUg/L CORT during early, mid or late larval stages grew and
developed slowly but tadpole morphology was not altered. Interestingly, exposure
during early or mid-larval stages resulted in an enhanced antipredator response.
These individuals metamorphosed later but at higher body mass while SVL was
unaffected.
PMID- 27613079
TI - Is diabetes mellitus correctly registered and classified in primary care? A
population-based study in Catalonia, Spain.
AB - OBJECTIVE: To assess the prevalence of miscoding, misclassification, misdiagnosis
and under-registration of diabetes mellitus (DM) in primary health care in
Catalonia (Spain), and to explore use of automated algorithms to identify them.
METHODS: In this cross-sectional, retrospective study using an anonymized
electronic general practice database, data were collected from patients or users
with a diabetes-related code or from patients with no DM or prediabetes code but
treated with antidiabetic drugs (unregistered DM). Decision algorithms were
designed to classify the true diagnosis of type 1 DM (T1DM), type 2 DM (T2DM),
and undetermined DM (UDM), and to classify unregistered DM patients treated with
antidiabetic drugs. RESULTS: Data were collected from a total of 376,278 subjects
with a DM ICD-10 code, and from 8707 patients with no DM or prediabetes code but
treated with antidiabetic drugs. After application of the algorithms, 13.9% of
patients with T1DM were identified as misclassified, and were probably T2DM;
80.9% of patients with UDM were reclassified as T2DM, and 19.1% of them were
misdiagnosed as DM when they probably had prediabetes. The overall prevalence of
miscoding (multiple codes or UDM) was 2.2%. Finally, 55.2% of subjects with
unregistered DM were classified as prediabetes, 35.7% as T2DM, 8.5% as UDM
treated with insulin, and 0.6% as T1DM. CONCLUSIONS: The prevalence of
inappropriate codification or classification and under-registration of DM is
relevant in primary care. Implementation of algorithms could automatically flag
cases that need review and would substantially decrease the risk of inappropriate
registration or coding.
PMID- 27613080
TI - Pineapple Genome: A Reference for Monocots and CAM Photosynthesis.
AB - Pineapple occupies an important phylogenetic position and its reference genome
expedites genomic research within the family Bromeliaceae and more widely among
monocots. One such research focus is the evolution of crassulacean acid
metabolism (CAM) photosynthesis. Acquiring circadian clock cis-regulatory
elements in CAM-related genes might be a critical step in the evolution of this
form of photosynthesis. Follow-up studies will clarify the processes and
evolutionary forces leading to the multiple independent origins of CAM
photosynthesis within the family Bromeliaceae and in over 400 genera across 36
families.
PMID- 27613081
TI - Exploring peer-mentoring for community dwelling older adults with chronic low
back pain: a qualitative study.
AB - OBJECTIVES: To explore the perceptions of patients, physiotherapists, and
potential peer mentors on the topic of peer-mentoring for self-management of
chronic low back pain following discharge from physiotherapy. DESIGN:
Exploratory, qualitative study. PARTICIPANTS: Twelve patients, 11 potential peer
mentors and 13 physiotherapists recruited from physiotherapy departments and
community locations in one health board area of the UK. INTERVENTIONS: Semi
structured interviews and focus groups. MAIN OUTCOME MEASURES: Participants'
perceptions of the usefulness and appropriateness of peer-mentoring following
discharge from physiotherapy. Data were processed and analysed using the
framework method. RESULTS: Four key themes were identified: (i) self-management
strategies, (ii) barriers to self-management and peer-mentoring, (iii) vision of
peer-mentoring, and (iv) the voice of experience. Peer-mentoring may be
beneficial for some older adults with chronic low back pain. Barriers to peer
mentoring were identified, and many solutions for overcoming them. No single
format was identified as superior; participants emphasised the need for any
intervention to be flexible and individualised. Important aspects to consider in
developing a peer-mentoring intervention are recruitment and training of peer
mentors and monitoring the mentor-mentee relationship. CONCLUSIONS: This study
has generated important knowledge that is being used to design and test a peer
mentoring intervention on a group of older people with chronic low back pain and
volunteer peer mentors. If successful, peer-mentoring could provide a cost
effective method of facilitating longer-term self-management of a significant
health condition in older people.
PMID- 27613082
TI - Physical activity participation in community dwelling stroke survivors: synergy
and dissonance between motivation and capability. A qualitative study.
AB - OBJECTIVES: The evidence supporting benefits of physical activity (PA) on
fitness, functioning, health and secondary prevention after stroke is compelling.
However, many stroke survivors remain insufficiently active. This study explored
survivors' perspectives and experiences of PA participation to develop an
explanatory framework that physiotherapists and other health professionals can
use to develop person-specific strategies for PA promotion. DESIGN: Qualitative
study using semi-structured in-depth interviews. Data was audio-recorded and
transcribed. Analysis followed the Framework Approach. SETTING: Community
setting, interviews conducted within participants' homes. PARTICIPANTS: Community
dwelling stroke survivors (n=38) six months or more after the end of their
rehabilitation, purposively selected by disability, PA participation and socio
demographic status. RESULTS: Findings suggest that survivors' beliefs, attitudes,
and physical and social context generated synergy or dissonance between
motivation (desire to be active) and capability (resources to be active) for PA
participation. Dissonance occurred when motivated survivors had limited
capability for activity, often leading to frustration. Confidence to achieve
goals and determination to overcome barriers, acted as activity catalysts when
other influences were synergistic. We illustrate these relationships in a dynamic
explanatory model that can be used to support both novel interventions and
personal activity plans. CONCLUSIONS: This study suggests a shift is required
from purely pragmatic approaches to PA promotion towards conceptual solutions.
Understanding how synergy or dissonance between motivation and capability
influence individual survivors' behaviour will support physiotherapists and other
health professionals in promoting PA. This study provides a model for developing
person-centred, tailored interventions that address barriers encountered by
stroke survivors.
PMID- 27613084
TI - Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth
Clinical Trial Methods.
AB - BACKGROUND: Randomized controlled trials (RCTs) have long been considered the
primary research study design capable of eliciting causal relationships between
health interventions and consequent outcomes. However, with a prolonged duration
from recruitment to publication, high-cost trial implementation, and a rigid
trial protocol, RCTs are perceived as an impractical evaluation methodology for
most mHealth apps. OBJECTIVE: Given the recent development of alternative
evaluation methodologies and tools to automate mHealth research, we sought to
determine the breadth of these methods and the extent that they were being used
in clinical trials. METHODS: We conducted a review of the ClinicalTrials.gov
registry to identify and examine current clinical trials involving mHealth apps
and retrieved relevant trials registered between November 2014 and November 2015.
RESULTS: Of the 137 trials identified, 71 were found to meet inclusion criteria.
The majority used a randomized controlled trial design (80%, 57/71). Study
designs included 36 two-group pretest-posttest control group comparisons (51%,
36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group
pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71),
and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a
qualitative component to their methodology (24%, 17/71). Complete trial data
collection required 20 months on average to complete (mean 21, SD 12). For trials
with a total duration of 2 years or more (31%, 22/71), the average time from
recruitment to complete data collection (mean 35 months, SD 10) was 2 years
longer than the average time required to collect primary data (mean 11, SD 8).
Trials had a moderate sample size of 112 participants. Two trials were conducted
online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite
study implementation was heavily favored (97%, 69/71). Trials with four data
collection points had a longer study duration than trials with two data
collection points: F4,56=3.2, P=.021, eta(2)=0.18. Single-blinded trials had a
longer data collection period compared to open trials: F2,58=3.8, P=.028,
eta(2)=0.12. Academic sponsorship was the most common form of trial funding (73%,
52/71). Trials with academic sponsorship had a longer study duration compared to
industry sponsorship: F2,61=3.7, P=.030, eta(2)=0.11. Combined, data collection
frequency, study masking, sample size, and study sponsorship accounted for 32.6%
of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7
trials had been completed at the time this retrospective review was conducted
(10%, 7/71). CONCLUSIONS: mHealth evaluation methodology has not deviated from
common methods, despite the need for more relevant and timely evaluations. There
is a need for clinical evaluation to keep pace with the level of innovation of
mHealth if it is to have meaningful impact in informing payers, providers, policy
makers, and patients.
PMID- 27613085
TI - Characterization of Rabbit Corneas Subjected to Stromal Stiffening by the Acai
Extract (Euterpe oleracea).
AB - PURPOSE: In this study, we characterized rabbit corneas subjected to corneal
cross-linking (CXL) with acai extract compared with a riboflavin photo-stimulated
procedure. MATERIALS AND METHODS: The corneas of the slaughterhouse rabbits were
divided into three groups: control, consisting of untreated corneal samples;
riboflavin/UVA, where corneas were treated with 0.1% riboflavin photo-stimulated
at 365 nm as the standard protocol; and acai, where the samples were subjected to
4% acai extract for 0.5-2 h. After the CXL procedure, corneas of the three groups
were characterized by analyzing their elastic modulus and thermal denaturation
profile. RESULTS: The elastic modulus at 3% strain showed an approximately
threefold increase in the riboflavin/UVA group and 10.5 times in the corneas
treated with 4% acai extract for 2 h, compared with the control group (p < 0.01).
The denaturation temperature values of the two groups of crosslinked corneas
increased significantly (p < 0.05) and were more pronounced in the acai group.
CONCLUSIONS: The acai extract was effective in promoting CXL in rabbit corneas as
characterized by the different techniques.
PMID- 27613083
TI - Variations in very preterm birth rates in 30 high-income countries: are valid
international comparisons possible using routine data?
AB - OBJECTIVE: Concerns about differences in registration practices across countries
have limited the use of routine data for international very preterm birth (VPT)
rate comparisons. DESIGN: Population-based study. SETTING: Twenty-seven European
countries, the United States, Canada and Japan in 2010. POPULATION: A total of 9
376 252 singleton births. METHOD: We requested aggregated gestational age data on
live births, stillbirths and terminations of pregnancy (TOP) before 32 weeks of
gestation, and information on registration practices for these births. We
compared VPT rates and assessed the impact of births at 22-23 weeks of gestation,
and different criteria for inclusion of stillbirths and TOP on country rates and
rankings. MAIN OUTCOME MEASURES: Singleton very preterm birth rate, defined as
singleton stillbirths and live births before 32 completed weeks of gestation per
1000 total births, excluding TOP if identifiable in the data source. RESULTS:
Rates varied from 5.7 to 15.7 per 1000 total births and 4.0 to 11.9 per 1000 live
births. Country registration practices were related to percentage of births at 22
23 weeks of gestation (between 1% and 23% of very preterm births) and stillbirths
(between 6% and 40% of very preterm births). After excluding births at 22-23
weeks, rate variations remained high and with a few exceptions, country rankings
were unchanged. CONCLUSIONS: International comparisons of very preterm birth
rates using routine data should exclude births at 22-23 weeks of gestation and
terminations of pregnancy. The persistent large rate variations after these
exclusions warrant continued surveillance of VPT rates at 24 weeks and over in
high-income countries. TWEETABLE ABSTRACT: International comparisons of VPT rates
should exclude births at 22-23 weeks of gestation and terminations of pregnancy.
PMID- 27613086
TI - Ecological Traits of the Algae-Bearing Tetrahymena utriculariae (Ciliophora) from
Traps of the Aquatic Carnivorous Plant Utricularia reflexa.
AB - Trap fluid of aquatic carnivorous plants of the genus Utricularia hosts specific
microbiomes consisting of commensal pro- and eukaryotes of largely unknown
ecology. We examined the characteristics and dynamics of bacteria and the three
dominant eukaryotes, i.e. the algae-bearing ciliate Tetrahymena utriculariae
(Ciliophora), a green flagellate Euglena agilis (Euglenophyta), and the alga
Scenedesmus alternans (Chlorophyta), associated with the traps of Utricularia
reflexa. Our study focused on ecological traits and life strategies of the highly
abundant ciliate whose biomass by far exceeds that of other eukaryotes and
bacteria independent of the trap age. The ciliate was the only bacterivore in the
traps, driving rapid turnover of bacterial standing stock. However, given the
large size of the ciliate and the cell-specific uptake rates of bacteria we
estimated that bacterivory alone would likely be insufficient to support its
apparent rapid growth in traps. We suggest that mixotrophy based on algal
symbionts contributes significantly to the diet and survival strategy of the
ciliate in the extreme (anaerobic, low pH) trap-fluid environment. We propose a
revised concept of major microbial interactions in the trap fluid where ciliate
bacterivory plays a central role in regeneration of nutrients bound in rapidly
growing bacterial biomass.
PMID- 27613087
TI - Effects of HA and NA glycosylation pattern changes on the transmission of avian
influenza A(H7N9) virus in guinea pigs.
AB - Avian influenza H7N9 virus has posed a concern of potential human-to-human
transmission by resulting in seasonal virus-like human infection cases. To
address the issue of sustained human infection with the H7N9 virus, here we
investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked
glycosylation (NLG) patterns on influenza virus transmission in a guinea pig
model. Based on the NLG signatures identified in the HA and NA genetic sequences
of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a
H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus
backbone. For the H7 HA NLG mutant viruses, NLG pattern changes appeared to
reduce viral transmissibility in guinea pigs. Intriguingly, however, the NLG
changes in the N9 NA protein, such as a removal from residue 42 or 66 or an
addition at residue 266, increased transmissibility of the mutant viruses by more
than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. Given
the effects of HA-NA NLG changes with regard to viral transmission, we then
generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition
and the N9 NA of various NLG patterns. As seen in the HA NLG mutants above, the
double NLG-added H7 HA decreased viral transmissibility. However, when the NA NLG
changes occurred by a removal of residue 66 and an addition at 266 were
additionally accompanied, the HA-NA NLG mutant virus recovered the
transmissibility of its parental virus. These demonstrate the effects of specific
HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance
of a HA-NA functional balance.
PMID- 27613088
TI - The low molecular weight fraction of commercial human serum albumin induces
acetylation of alpha-tubulin and reduces transcytosis in retinal endothelial
cells.
AB - It has long been appreciated that the microtubule network plays a critical role
in endothelial cell function. Chemical inhibition of tubulin polymerization has
been shown to drastically increases endothelial permeability via interactions
with the actin cytoskeleton. Conversely, stabilization of microtubules
significantly decreases vascular permeability. The purpose of this investigation
was to determine if the low molecular weight fraction of commercial 5% human
serum albumin (LMWF5A) alters endothelial cell cytoskeletal dynamics and
function. To investigate this, human retinal endothelial cells (HREC) were
treated with LMWF5A and the acetylation of alpha-tubulin was determined by
immunofluorescent staining and immunoblotting. In addition, permeability assays
were performed to evaluate functional changes. We found that HREC treated with
LMWF5A exhibit a rapid increase in the amount and distribution of acetylated
alpha-tubulin. This was accompanied by a reduction in macromolecular
permeability. Calcium depletion and inhibition of PI3-kinase reduced LMWF5A
induced acetylation while p38 MAPK inhibition potentiated this effect. These
findings suggest that LMWF5A mediates changes in the microtubule network and
reduces transcytosis in HREC.
PMID- 27613089
TI - MiR-1271 upregulated by saturated fatty acid palmitate provokes impaired insulin
signaling by repressing INSR and IRS-1 expression in HepG2 cells.
AB - Dietary saturated fatty acids (SFA) in excess not only induce hepatic insulin
resistance, but also result in type 2 diabetes (T2DM). Although microRNAs
(miRNAs) participate widely in the pathogenesis of a range of diseases through
the suppression of target gene expression at the post-transcriptional level, the
implications of SFA-induced miRNAs in the dysregulation of metabolism,
particularly in the development of insulin resistance, are largely unclear. SFA
palmitate provoked an impairment of insulin signaling in HepG2 cells via a
reduction in the expression of INSR and IRS-1 protein. The significant
upregulation of miR-1271, which was presumed to target INSR and IRS-1 3'UTRs, was
observed in the palmitate-treated HepG2 cells. Using a reporter gene assay, miR
1271 authentically targeted the 3'UTRs of INSR and IRS-1. Furthermore, the
overexpression of miR-1271 caused a substantial decrease in INSR and IRS-1
expression, which led to an impairment in insulin signaling and glycogen
metabolism. Therefore, these findings suggest that the induction of miR-1271 by
SFA palmitate promotes the development of insulin resistance by targeting INSR
and IRS-1 in hepatocytes.
PMID- 27613090
TI - Identification of miR-125b targets involved in acute promyelocytic leukemia cell
proliferation.
AB - Acute promyelocytic leukemia (APL) is characterized by the presence of the PML
RARalpha fusion protein. We have previously found that PML-RARalpha-regulated miR
125b is highly expressed in APL; however, the characteristics of the regulatory
effects and mechanisms of miR-125b involved in APL proliferation have yet to be
clarified. In this study, we demonstrate that miR-125b promotes the proliferation
of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways.
Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets
of miR-125b, which we verified using luciferase reporter constructs. Moreover, we
demonstrate that the expression of miR-125b targets is downregulated in leukemic
cells in patients with APL. Thus, our results provide evidence that miR-125b can
modulate multiple oncogenic cell proliferation pathways and may be a novel
therapeutic target for APL.
PMID- 27613091
TI - An ubiquitin-binding molecule can work as an inhibitor of ubiquitin processing
enzymes and ubiquitin receptors.
AB - The ubiquitin pathway plays a critical role in regulating diverse biological
processes, and its dysregulation is associated with various diseases. Therefore,
it is important to have a tool that can control the ubiquitin pathway in order to
improve understanding of this pathway and to develop therapeutics against
relevant diseases. We found that Chicago Sky Blue 6B binds directly to the beta
groove, a major interacting surface of ubiquitin. Hence, it could successfully
inhibit the enzymatic activity of ubiquitin processing enzymes and the binding of
ubiquitin to the CXCR4, a cell surface ubiquitin receptor. Furthermore, we
demonstrated that this ubiquitin binding chemical could effectively suppress the
ubiquitin induced cancer cell migration by blocking ubiquitin-CXCR4 interaction.
Current results suggest that ubiquitin binding molecules can be developed as
inhibitors of ubiquitin-protein interactions, which will have the value not only
in unveiling the biological role of ubiquitin but also in treating related
diseases.
PMID- 27613092
TI - PMCA2 silencing potentiates MDA-MB-231 breast cancer cell death initiated with
the Bcl-2 inhibitor ABT-263.
AB - PMCA2 overexpression in some breast cancers suggests that this calcium pump
isoform may play a role in breast pathophysiology. To investigate PMCA2 as a
potential drug target for breast cancer therapy, we assessed the functional
consequence of PMCA2 silencing on cell death pathways and calcium signals in the
basal-like MDA-MB-231 breast cancer cell line. Silencing PMCA2 expression alone
has no effect on MDA-MB-231 cell viability, however, PMCA2 silencing promotes
calcium-induced cell death initiated with the calcium ionophore ionomycin.
Assessment of cytoplasmic calcium responses generated with various agents
including ionomycin demonstrates that in MDA-MB-231 cells, PMCA2 does not play a
major role in shaping global calcium signals. We also examined the ability of
PMCA2 silencing to modulate caspase-dependent cell death triggered by a Bcl-2
inhibitor that is in clinical development for the treatment of various cancers,
ABT-263 (Navitoclax). Despite the lack of effect on global calcium responses,
PMCA2 silencing augmented Bcl-2 inhibitor (ABT-263)-mediated MDA-MB-231 breast
cancer cell death. These studies provide evidence that PMCA2 inhibitors could
sensitize PMCA2-positive breast cancers to cell death initiators that work
through mechanisms involving the Bcl-2 survival pathway.
PMID- 27613093
TI - Redox regulation of ATP sulfurylase in microalgae.
AB - ATP sulfurylase (ATPS) catalyzes the first step of sulfur assimilation in
photosynthetic organisms. An ATPS type A is mostly present in freshwater
cyanobacteria, with four conserved cysteine residues. Oceanic cyanobacteria and
most eukaryotic algae instead, possess an ATPS-B containing seven to ten
cysteines; five of them are conserved, but only one in the same position as ATPS
A. We investigated the role of cysteines on the regulation of the different algal
enzymes. We found that the activity of ATPS-B from four different microorganisms
was enhanced when reduced and decreased when oxidized. The LC-MS/MS analysis of
the ATPS-B from the marine diatom Thalassiosira pseudonana showed that the
residue Cys-247 was presumably involved in the redox regulation. The absence of
this residue in the ATPS-A of the freshwater cyanobacterium Synechocystis sp.
instead, was consistent with its lack of regulation. Some other conserved
cysteine residues in the ATPS from T. pseduonana and not in Synechocystis sp.were
accessible to redox agents and possibly play a role in the enzyme regulation.
Furthermore, the fact that oceanic cyanobacteria have ATPS-B structurally and
functionally closer to that from most of eukaryotic algae than to the ATPS-A from
other cyanobacteria suggests that life in the sea or freshwater may have driven
the evolution of ATPS.
PMID- 27613094
TI - Long non-coding RNA HOTAIR promotes ischemic infarct induced by hypoxia through
up-regulating the expression of NOX2.
AB - BACKGROUND: Mounting studies have illustrated an important role of HOTAIR in
cancer progress, but few studies have reported its function in brain disease,
including nerve cell-associated ischemic infarct. This study aimed to investigate
the function of HOTAIR in ischemic infarct, involving its association with the
level of NOX2 during hypoxia-induced ischemic infarct. METHODS: Ischemic infarct
mice model was established by hypoxia induction, and cerebral dysfunction was
evaluated with the surface cerebral blood flow in the ipsilateral hemisphere.
HOTAIR expression in isolated infarction lesion and NOX2 protein level in the
circulation were detected. HT22 cells were subjected to hypoxia treatment in
vitro for functional studies, including TUNEL-positive cells detection for
apoptosis analysis. RESULTS: HOTAIR expression was significantly up-regulated in
infarction lesion from ischemic infarct mice, in line with increased NOX2
production, while similar results were also observed in hypoxia treated HT22
cells, which was then reversed by HOTAIR interference. Functional studies
demonstrated that HOTAIR showed positive regulation on TUNEL-positive cells and
apoptosis. Further in vitro study confirmed that HOTAIR silencing could improve
cerebral function of ischemic infarct mice, and markedly decreased NOX2
production in the circulation. CONCLUSION: High expression of HOTAIR promoted the
onset of ischemic infarct induced by hypoxia. Moreover, the finding showed that
HOTAIR promoted ischemic infarct induced by hypoxia through regulating NOX2
expression, which could add our understanding of the molecular mechanisms in
ischemic infarct.
PMID- 27613095
TI - The development of a single molecule fluorescence standard and its application in
estimating the stoichiometry of the nuclear pore complex.
AB - We report here an image-based method to quantify the stoichiometry of diffraction
limited sub-cellular protein complexes in vivo under spinning disk confocal
microscopy. A GFP single molecule fluorescence standard was first established by
immobilizing His-tagged GFP molecules onto the glass surface via nickel
nitrilotriacetic acid functionalized polyethylene glycol. When endogenous
nucleoporins were knocked down and replaced by the exogenously expressed and
knockdown-resistant GFP-nucleoporins, the stoichiometry of the nucleoporin was
estimated by the ratio of its fluorescence intensity to that of the GFP single
molecules. Our measured stoichiometry of Nup35, Nup93, Nup133 and Nup88 is 23,
18, 14 and 9 and there are possibly16 copies of Nup107-160 complex per nuclear
pore complex.
PMID- 27613096
TI - Human Rad23A plays a regulatory role in autophagy.
AB - Chemotherapeutic agents can upregulate autophagy which contributes to the
acquisition of chemoresistance and the recurrence of cancer. The involvement of
hHR23A in chemoresistance is unknown. In this study, we provide evidence
suggesting that hHR23A may regulate autophagy. Knockdown of hHR23A decreased cell
growth and increased the resistance in A549 cells to the DNA-damaging agents,
cisplatin and oxaliplatin. Measurement of EGFP-LC3 puncta (a marker of autophagy)
revealed that autophagy was increased in hHR23A-depleted cells. This effect was
augmented by exposure to cisplatin or oxaliplatin. In contrast, the
overexpression of hHR23A reversed the levels of autophagy-related proteins to
control levels in hHR23A-knockdown cells. Moreover, we observed direct
interactions among hHR23A, Beclin 1, and LC3. Finally, 3-methyladenine (3-MA)
induced inhibition of autophagy was found to reverse the sensitivity of hHR23A
knockdown cells to the tested DNA-damaging agents. These results collectively
indicated that hHR23A-depleted cells exhibit enhanced autophagy when treated with
DNA-damaging agents, perhaps suggesting a basis for the involvement of hHR23A in
the acquired chemoresistance of cancer cells. Our study thus reveals a previously
unrecognized autophagic function for hHR23A and suggests that it could be a
potential therapeutic target for chemosensitizing resistant cancer cells.
PMID- 27613097
TI - The effect of H19-miR-29b interaction on bleomycin-induced mouse model of
idiopathic pulmonary fibrosis.
AB - Pulmonary fibrosis, characterized by the destruction of lung tissue architecture
and the formation of fibrous foci, currently has no satisfactory treatment.
Emodin is a component of Chinese herb that has been reported to be medicable on
pancreatic fibrosis and liver fibrosis. However, its role in pulmonary fibrosis
has not been reported yet. In the present study, we investigated the hypothesis
that H19 play a promotive role in bleomycin-induced epithelial-mesenchymal
transition of alveolar epithelial cell, and H19 exerts its effect through miR-29b
regulation. H19 expression was positively correlated with COL1A1 and Acta2
expression; H19 knockdown inhibited COL1A1 and Acta2 expression. Moreover, H19
interacted with miR-29b through directly binding to the 3'UTR; miR-29b inhibited
COL1A1 expression by directly binding to the 3'UTR. In conclusion, we revealed
the promotive effect of H19 on BLM-induced IPF, and demonstrated the mechanism by
which H19/miR-29b interaction exerts its effect on regulating pulmonary fibrosis.
The present study provided a potential therapy to treat IPF.
PMID- 27613098
TI - Tools for the rational design of bivalent microtubule-targeting drugs.
AB - Microtubule (MT) dynamic behaviour is an attractive drug target for chemotherapy,
whose regulation by MT-stabilizing and destabilizing agents has been fruitfully
applied in treating several types of cancers. MT-stabilizing agents are also
emerging as potential remedies for neurodegenerative conditions, such as
Alzheimer's and Parkinson's disease, although single-target drugs are not
expected to fully cure these complex pathologies. Drug combination often displays
enhanced efficacy with respect to mono-therapies. In particular, MT-targeting
bivalent compounds (MTBCs) represent a promising class of molecules; however,
surprisingly, the majority of MTBCs reported so far exhibit equal if not less
efficacy than their building monomers. In order to shed light on MTBCs poor
performance, we characterised through a set of complementary approaches
thiocolchine (TH) and two bivalent TH-homodimers as prototype molecules. First,
the binding affinities of these three molecules were assessed, then we obtained
the crystallographic structure of a tubulin-TH complex. The binding affinities
were interpreted in light of structural data and of molecular dynamics
simulations. Finally, their effects on MT cytoskeleton and cell survival were
validated on HeLa cells. The ensemble of these data provides chemical and
structural considerations on how a successful rational design of MTBCs should be
conceived.
PMID- 27613100
TI - Chemokines, cytokines and exosomes help tumors to shape inflammatory
microenvironment.
AB - Relationship between inflammation and cancer is now well-established and
represents a paradigm that our immune response does not necessarily serves solely
to protect us from infections and cancer. Many specific mechanisms that link
chronic inflammation to cancer promotion and metastasis have been uncovered in
the recent years. Here we are focusing on the effects that tumors may exert on
inflammatory cascades, tuning the immune system ability to cause tumor promotion
or regression. In particular, we discuss the contributions of chemokines,
cytokines and exosomes to the processes such as induction of inflammation and
tumorigenesis. Overall, tumor-elicited inflammation is a key driver of tumor
progression and an essential component of tumor microenvironment.
PMID- 27613099
TI - Genetic polymorphisms of eNOS (-786T/C, Intron 4b/4a & 894G/T) and its
association with asymptomatic first degree relatives of coronary heart disease
patients.
AB - BACKGROUND: The eNOS gene has been extensively screened for important variations
in the promoter (-786T/C), Intron 4 (4b/4a) and exon 7 (894G/T) regions in
multiple diseases. Prevalence of Coronary Heart Disease (CHD) is much higher in
young Indians when compared to other ethnic groups and first-degree relatives
(FDRS) of CHD patients are at risk correlating with earlier age-of-onset and poor
prognosis. OBJECTIVE: The objective of this study is to understand the genetic
mechanism of eNOS -786T/C, Intron 4b/4a and 894G/T polymorphisms/haplotypes in
the development of CHD and to identify individuals having coronary risk factors
among the FDRS of CHD patients by comparing them with the general population.
MATERIALS & METHODS: The study population consisted of 300 CHD patients with
angiographically documented, 100 FDRS and 300 age and sex matched healthy
controls. Genotyping of eNOS -786T/C, Intron 4b/4a was carried out by Allele
specific-Polymerase Chain Reaction (As-PCR) and 894G/T by PCR-restriction
fragment length polymorphism (PCR-RFLP) assays. RESULTS: The frequency of risk
factors for CHD includes age, blood pressure, obesity, diabetes mellitus,
smoking, non-vegetarian diet, family history are higher in CHD patients and FDRS
compared to controls (p < 0.01). The genotype distribution, allele frequencies
and haplotypes of the eNOS -786T/C, 4b/4a and 894G/T were significantly different
between CHD patients, FDRS and controls. eNOS gene haplotypes GCB, TCB (G-allele
of 894G/T, C-allele -786T/C, B-allele of Intron 4b/4a respectively) were
associated with high nitrite/nitrate levels compared to GTB in both FDRS and CHD
patients (p < 0.01). CONCLUSION: The study shows the importance of eNOS
polymorphism in the pathogenesis of CHD and predicting the risk of future
coronary events in asymptomatic healthy FDRS and suggests the use of new
therapeutics and initiating the measures for prevention or delaying the
progression of the disease by life style modification or treatment modalities in
high-risk individuals.
PMID- 27613101
TI - Inhibition of B-cell activation and antibody production by triggering inhibitory
signals via the PD-1/PD-ligand pathway.
AB - BACKGROUND: The development of donor-reactive antibodies is regarded to be an
important barrier limiting long-term outcome of allo- and xenografts. We asked
whether enhanced signaling via the co-inhibitory receptor programmed cell death-1
(PD-1; CD279) can downregulate human B-cell activation. METHODS: Proliferation of
human purified CD19(+) B cells was induced by in vitro stimulation with CpG
oligodeoxynucleotides (CpG-B). To induce antibody production, peripheral blood
mononuclear cells were co-cultured with the porcine B-cell line L23. Triggering
of inhibitory signals via the PD-1 receptor was obtained either using a
recombinant agonistic soluble ligand (PD-L1.Ig) or L23 transfectants
overexpressing membrane-bound human PD-L1 (CD274; L23-PD-L1 cells). RESULTS:
Stimulation of purified CD19(+) B cells with CpG-B resulted in upregulation of PD
1 and strong proliferation. Addition of PD-L1.Ig significantly reduced B-cell
proliferation in a dose-dependent manner. A great proportion (~1%) of human
circulating B cells recognizes the epitope galactose-alpha1,3-galactose-beta1,4-N
acetylglucosamine-R (alpha-gal). Thus, when B cells-in the presence of T cell
help-were cocultured with alpha-gal-expressing L23 cells, anti-gal and anti-L23
antibodies could readily be detected in the culture supernatant. The level of
induced antibodies was significantly reduced when stimulation was performed by
L23-PD-L1 cells. CONCLUSIONS: Enhancing inhibitory signals may be part of future
protocols to better control humoral immunity to allo- and xenografts.
PMID- 27613102
TI - The prevalence of obesity and influence of early life and behavioral factors on
obesity in Chinese children in Guangzhou.
AB - BACKGROUND: Childhood obesity has become a public health concern in many
countries. In Southern China, the prevalence of childhood obesity increased from
6.2 to 7.5 % between 2007 and 2011. This study aimed to report the current
prevalence of overweight and obesity, analyzed the early life and behavioral
determinants of obesity, and investigated the weight-loss practices among Chinese
children in Guangzhou. METHODS: Three thousand seven hundred sixty-six primary
school students aged 7-12 years were recruited in Guangzhou, China in 2013.
Questionnaires were used to assess (1) early life factors: birth weight, delivery
mode, gestational age and feeding patterns; (2) behavioral factors: dietary
intake, eating speed, sedentary time, physical activities and sleep duration; and
(3) weight-loss practices: improving diet, increasing exercise, taking weight
loss drugs and undergoing a diet. The criteria of Working Group of Obesity in
China were applied to classify overweight and obesity based on measured weight
and height. Multivariable logistic regression analyses were performed to examine
the determinants of overweight/obesity and adoption of weight-loss practices.
RESULTS: The prevalence of childhood overweight and obesity were 11.2 and 10.0 %,
respectively. High birth weight (>=4.0 kg versus 2.5 ~ 4.0 kg, odd ratio [OR]:
2.34; 95 % confidence interval [CI]: 1.53-3.58), sugar-sweetened beverages (SSBs)
intake (OR: 1.39; 95 % CI: 1.05-1.85), vegetable intake (OR: 1.12; 95 % CI: 1.01
1.24), and doing homework (OR: 1.24; 95 % CI: 1.08-1.43) were positively
associated with obesity. Eating speed faster than peers was positively associated
with obesity and yielded the highest OR (versus "as fast as peers", OR: 3.18; 95
% CI: 2.28-4.44). Approximately 57, 81 and 87 % of normal-weight, overweight and
obese children, respectively, reported weight-loss practices. Self-perception of
weight status presented as the strongest determinant for weight-loss practices.
CONCLUSIONS: The prevalence of overweight and obesity were high in Chinese
children in Guangzhou, and both were higher than previous level in 2011. Further
research should address the unhealthy dietary (e.g. SSBs intake, fast eating
speed) and sedentary behaviors (e.g. doing homework) of these children. Moreover,
an accurate perception of body weight can help promote the adoption of weight
loss practices in overweight and obese children.
PMID- 27613103
TI - Emticiciafontis sp. nov., isolated from a freshwater pond.
AB - A bacterial strain, designated IMCC1731T, was isolated from an eutrophic
freshwater pond and characterized using a polyphasic taxonomic approach. Cellular
growth occurred at pH 6-9 (optimum, pH 8.0), at 10-30 degrees C (optimum, 25
degrees C) and with 0-1 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based
on 16S rRNA gene sequences indicated that strain IMCC1731T belonged to the genus
Emticicia in the family Cytophagaceae and was most closely related to Emticicia
ginsengisoli Gsoil 085T (98.1 %) followed by Emticicia paludis HMF3850T (95.0 %),
Emticicia oligotrophica DSM 17448T (94.7 %), Emticicia aquatica HMF2925T (94.4 %)
and Emticicia sediminis JBR12T (94.0 %). The DNA-DNA relatedness between strain
IMCC1731T and E. ginsengisoli Gsoil 085T was 47+/-4 %. The DNA G+C content of
strain IMCC1731T was 37.7 mol%. The predominant cellular fatty acids were summed
feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and iso-C15 : 0. Based on the
physiological and chemotaxonomic characteristics, DNA-DNA relatedness and 16S
rRNA gene phylogeny, stain IMCC1731T is considered to represent a novel species
of the genus Emticicia, for which the name Emticicia fontis sp. nov. is proposed.
The type strain is IMCC1731T (=KCTC 52248T=JCM 31373T).
PMID- 27613104
TI - Management of blight of bell pepper (Capsicum annuum var. grossum) caused by
Drechslera bicolor.
AB - Sweet or bell pepper is a member of the Solanaceae family and is regarded as one
of the most popular and nutritious vegetable. Blight, in the form of leaf and
fruit blight, has been observed to infect bell pepper crops cultivated at the
horticulture farm in Rajasthan College of Agriculture, Udaipur, India. Based on
disease severity, we attempted to curb this newly emerged problem using different
fungicides, plant extracts, bio-control agents, and commercial botanicals against
the fungus in laboratory and pot experiments. Bio-control agent Trichoderma
viride and plant growth promoting Rhizobacteria (PGPR) isolate Neist-2 were found
to be quite effective against bell pepper blight. All evaluated fungicides,
botanicals, commercial botanicals, and bio-control agents in vitro were further
studied as seed dressers and two foliar sprays at ten days interval in pot
experiments. The combinations of Vitavax, PGPR isolate Neist-2, and Mehandi
extract were found to be very effective against bell pepper blight followed by
Vitavax, T. viride, and Mehandi extract used individually. All treatments in the
pot experiments were found to significantly reduce seedling mortality and enhance
plant biomass of bell pepper. Thus, these experimental findings suggest that a
better integrated management of bell pepper blight could be achieved by
conducting field trials in major bell pepper- and chilli-cultivated areas of the
state. Besides fungicides, different botanicals and commercial botanicals also
seem to be promising treatment options. Therefore, the outcome of the present
study provides an alternate option of fungicide use in minimizing loss caused by
Drechslera bicolor.
PMID- 27613105
TI - Differences in the Rate of in Situ Mammary Gland Development and Other
Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary
Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure.
AB - The potential of chemicals to alter susceptibility to mammary tumor formation is
often assessed using a carcinogen-induced study design in various rat strains.
The rate of mammary gland (MG) development must be considered so that the timing
of carcinogen administration is impactful. In this study, in situ MG development
was assessed in females of the Harlan Sprague-Dawley (Hsd:SD), Charles River
Sprague-Dawley (Crl:SD), and Charles River Long-Evans (Crl:LE) rat strains at
postnatal days 25, 33, and 45. Development was evaluated by physical assessment
of growth parameters, developmental scoring, and quantitative morphometric
analysis. Although body weight (BW) was consistently lower and day of vaginal
opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated
pre- and peripubertal MG development compared to other strains. Glands of Crl:SD
and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm
than Hsd:SD rats around the time of VO. These data suggest a considerable
difference in the rate of MG development across commonly used strains, which is
independent of BW and timing of VO. In mammary tumor induction studies employing
these strains, administration of the carcinogen should be timed appropriately,
based on strain, to specifically target the peak of TEB occurrence.
PMID- 27613106
TI - Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental
Patterns in the Male and Female Harlan Sprague-Dawley Rat.
AB - There are currently no reports describing mammary gland development in the Harlan
Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology
Program (NTP) testing. Our goals were to empower the NTP, contract labs, and
other researchers in understanding and interpreting chemical effects in this rat
strain. To delineate similarities/differences between the female and male mammary
gland, data were compiled starting on embryonic day 15.5 through postnatal day
70. Mammary gland whole mounts, histology sections, and immunohistochemically
stained tissues for estrogen, progesterone, and androgen receptors were evaluated
in both sexes; qualitative and quantitative differences are highlighted using a
comprehensive visual timeline. Research on endocrine disrupting chemicals in
animal models has highlighted chemically induced mammary gland anomalies that may
potentially impact human health. In order to investigate these effects within the
HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle
control was gavage dosed on gestation day 15 and 18 to demonstrate delayed,
accelerated, and control mammary gland growth in offspring, respectively. We
provide illustrations of normal and chemically altered mammary gland development
in HSD male and female rats to help inform researchers unfamiliar with the tissue
and may facilitate enhanced evaluation of both male and female mammary glands in
juvenile toxicity studies.
PMID- 27613109
TI - Adaptive evolution of seed oil content in angiosperms: accounting for the global
patterns of seed oils.
AB - BACKGROUND: Studies of the biogeographic distribution of seed oil content in
plants are fundamental to understanding the mechanisms of adaptive evolution in
plants as seed oil is the primary energy source needed for germination and
establishment of plants. However, seed oil content as an adaptive trait in plants
is poorly understood. Here, we examine the adaptive nature of seed oil content in
168 angiosperm families occurring in different biomes across the world. We also
explore the role of multiple seed traits like seed oil content and composition in
plant adaptation in a phylogenetic and nonphylogenetic context. RESULT: It was
observed that the seed oil content in tropical plants (28.4 %) was significantly
higher than the temperate plants (24.6 %). A significant relationship between oil
content and latitude was observed in three families Papaveraceae, Sapindaceae and
Sapotaceae indicating that selective forces correlated with latitude influence
seed oil content. Evaluation of the response of seed oil content and composition
to latitude and the correlation between seed oil content and composition showed
that multiple seed traits, seed oil content and composition contribute towards
plant adaptation. Investigation of the presence or absence of phylogenetic
signals across 168 angiosperm families in 62 clades revealed that members of
seven clades evolved to have high or low seed oil content independently as they
did not share a common evolutionary path. CONCLUSION: The study provides us an
insight into the biogeographical distribution and the adaptive role of seed oil
content in plants. The study indicates that multiple seed traits like seed oil
content and the fatty acid composition of the seed oils determine the fitness of
the plants and validate the adaptive hypothesis that seed oil quantity and
quality are crucial to plant adaptation.
PMID- 27613107
TI - Contribution of type W human endogenous retroviruses to the human genome:
characterization of HERV-W proviral insertions and processed pseudogenes.
AB - BACKGROUND: Human endogenous retroviruses (HERVs) are ancient sequences
integrated in the germ line cells and vertically transmitted through the
offspring constituting about 8 % of our genome. In time, HERVs accumulated
mutations that compromised their coding capacity. A prominent exception is HERV-W
locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for
placental syncytiotrophoblast formation. While expression of HERV-W sequences has
been investigated for their correlation to disease, an exhaustive description of
the group composition and characteristics is still not available and current HERV
W group information derive from studies published a few years ago that, of
course, used the rough assemblies of the human genome available at that time.
This hampers the comparison and correlation with current human genome assemblies.
RESULTS: In the present work we identified and described in detail the
distribution and genetic composition of 213 HERV-W elements. The bioinformatics
analysis led to the characterization of several previously unreported features
and provided a phylogenetic classification of two main subgroups with different
age and structural characteristics. New facts on HERV-W genomic context of
insertion and co-localization with sequences putatively involved in disease
development are also reported. CONCLUSIONS: The present work is a detailed
overview of the HERV-W contribution to the human genome and provides a robust
genetic background useful to clarify HERV-W role in pathologies with poorly
understood etiology, representing, to our knowledge, the most complete and
exhaustive HERV-W dataset up to date.
PMID- 27613108
TI - The ethical issues regarding consent to clinical trials with pre-term or sick
neonates: a systematic review (framework synthesis) of the analytical
(theoretical/philosophical) research.
AB - BACKGROUND: Conducting clinical trials with pre-term or sick infants is important
if care for this population is to be underpinned by sound evidence. Yet,
approaching the parents of these infants at such a difficult time raises
challenges to obtaining valid informed consent for such research. In this study,
we asked, What light does the analytical literature cast on an ethically
defensible approach to obtaining informed consent in perinatal clinical trials?
METHODS: In a systematic search, we identified 30 studies. We began our analysis
by applying philosophical frameworks, which were then refined as concepts emerged
from the analytical studies, to present a coherent picture of a broad literature.
RESULTS: Between them, the studies addressed four themes. The first three were
the ethical basis for parental informed consent for neonatal and/or perinatal
research, the validity of parental consent in this context, and the range of
possible options in methods for gaining consent. The last was the issue of risk
and the possibility of a double-standard or asymmetry in the current approaches
to the requirement for consent for research and consent for clinical treatment.
CONCLUSIONS: In addressing these issues, the analysed studies showed that, whilst
there are a variety of possible defences for seeking parental 'consent' to
neonatal and/or perinatal clinical trials, these are all consistent with the
strongly and widely held view that it is important that parents do give (or
decline) consent for such research. So far as the method of obtaining consent is
concerned, none of the existing consent processes reviewed by the research is
satisfactory, and there are philosophical reasons for supposing that at least
some parents will fail to give valid consent in a neonatal context. Furthermore,
in giving parental 'consent' in a perinatal context, parents are authorising
infant participation, not giving 'proxy consent'. Finally, there are reasons for
giving weight to both parental 'consent' and the infant's best interests in both
research and clinical treatment. However, there are also reasons to treat these
factors differently in the two contexts, and this may be partly due to the
differing relevance of risk in each case. A significant gap is the lack of any
detailed discussion of a process of emergency and/or urgent 'assent', in which
parents assent or refuse their baby's participation as best they can during the
emergency and later give full consent to continuing participation and follow-up.
PMID- 27613111
TI - Relationship between women's characteristics and continuum of care for maternal
health in Kenya: Complex survey analysis using structural equation modeling.
AB - The objective of this study was to understand and estimate the complex
relationships in the continuum of care for maternal health to provide information
to improve maternal and newborn health outcomes. Women (n = 4,082) aged 15-49
years in the 2008/2009 Kenya Demographic and Health Survey data were used to
explore the complex relationships in the continuum of care for maternal health
(i.e., before, during, and after delivery) using structural equation modeling.
Results showed that the use of antenatal care was significantly positively
related to the use of delivery care (beta = 0.06; adjusted odds ratio [AOR] =
1.06; 95% confidence interval [CI]: 1.02-1.10) but not postnatal care, while
delivery care was associated with postnatal care (beta = 0.68; AOR = 1.97; 95%
CI: 1.75-2.22). Socioeconomic status was significantly related to all elements in
the continuum of care for maternal health; barriers to delivery of care and
personal characteristics were only associated with the use of delivery care (beta
= 0.34; AOR = 1.40; 95% CI: 1.30-1.52) and postnatal care (beta = 0.03; AOR =
1.03; 95% CI: 1.01-1.05), respectively. The three periods of maternal health care
were related to each other. Developing a referral system of continuity of care is
critical in the Sustainable Development Goals era.
PMID- 27613110
TI - Increased skin autofluorescence of children and adolescents with type 1 diabetes
despite a well-controlled HbA1c: results from a cohort study.
AB - BACKGROUND: Early identification of children and adolescents with type 1 diabetes
at high risk for development of complications is important, as early intervention
may prevent further deterioration. Here we investigate the applicability of
assessing skin advanced glycation end products (sAGEs) by skin autofluorescence
(SAF) as a potential surrogate risk marker. METHODS: This study included a cross
sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118
healthy controls across age categories (11-12, 13-14, 15-16, and 17-19 years
old). In patients, the impact of current and historical glycated hemoglobin
(HbA1c) values, age, and duration of diabetes on SAF was studied in a
retrospective cohort study and analyzed with multivariable analyses. RESULTS: SAF
was significantly and similarly higher in patients when compared with controls
across all age categories (P <=0.009). For patients, age, duration of diabetes,
and current and historical HbA1c were associated with SAF in univariate analysis.
Multivariate analysis showed no association between HbA1c and SAF. A subgroup of
patients with a HbA1c-within-target (<=7.5 %/59 mmol/mol) were observed to have
high SAF. CONCLUSION: Children and adolescents with type 1 diabetes show higher
SAF than controls. The presumed correlation of high HbA1c with high SAF does not
exist in all patients. Thus, use of this non-invasive measure may provide a
surrogate marker for diabetic complications, additional to HbA1c.
PMID- 27613112
TI - Gene Ontology synonym generation rules lead to increased performance in
biomedical concept recognition.
AB - BACKGROUND: Gene Ontology (GO) terms represent the standard for annotation and
representation of molecular functions, biological processes and cellular
compartments, but a large gap exists between the way concepts are represented in
the ontology and how they are expressed in natural language text. The
construction of highly specific GO terms is formulaic, consisting of parts and
pieces from more simple terms. RESULTS: We present two different types of
manually generated rules to help capture the variation of how GO terms can appear
in natural language text. The first set of rules takes into account the
compositional nature of GO and recursively decomposes the terms into their
smallest constituent parts. The second set of rules generates derivational
variations of these smaller terms and compositionally combines all generated
variants to form the original term. By applying both types of rules, new synonyms
are generated for two-thirds of all GO terms and an increase in F-measure
performance for recognition of GO on the CRAFT corpus from 0.498 to 0.636 is
observed. Additionally, we evaluated the combination of both types of rules over
one million full text documents from Elsevier; manual validation and error
analysis show we are able to recognize GO concepts with reasonable accuracy (88
%) based on random sampling of annotations. CONCLUSIONS: In this work we present
a set of simple synonym generation rules that utilize the highly compositional
and formulaic nature of the Gene Ontology concepts. We illustrate how the
generated synonyms aid in improving recognition of GO concepts on two different
biomedical corpora. We discuss other applications of our rules for GO ontology
quality assurance, explore the issue of overgeneration, and provide examples of
how similar methodologies could be applied to other biomedical terminologies.
Additionally, we provide all generated synonyms for use by the text-mining
community.
PMID- 27613113
TI - Characterize the relationship between essential and TATA-containing genes for S.
cerevisiae by network topologies in the perturbation sensitivity network.
AB - Essential genes are those that are indispensable for the survival and propagation
of an organism. TATA-containing genes are associated with responses to various
stresses and are highly regulated. Although both essential genes and TATA genes
are very important in the function of biological systems, their relationship
remains unclear because they have typically been researched independently. In
this study, to investigate the relationship between essential genes and TATA
genes, S. cerevisiae genes were classified as: essential TATA-containing, non
essential TATA-containing, essential non-TATA, and non-essential non-TATA genes.
Network-based methods were applied to analyze these four gene categories in the
S. cerevisiae perturbation sensitivity (PS) network, which was created from the
transcriptional profiling of hundreds of different gene disruptions. All of the
topological properties were found to be statistically discriminative among the
four gene categories, and the non-essential TATA-containing genes had the most
important roles in the yeast PS network.
PMID- 27613115
TI - Editorial Comment.
PMID- 27613116
TI - Reply by Authors.
PMID- 27613114
TI - Genetic causes of Parkinson's disease in the Maltese: a study of selected
mutations in LRRK2, MTHFR, QDPR and SPR.
AB - BACKGROUND: Mutations in Leucine-rich repeat kinase 2 NM_198578 (LRRK2 c.6055G >
A (p.G2019S), LRRK2 c.4321C > G (p.R1441G)) and alpha-synuclein NM_000345 (SNCA
c.209G > A (p.A53T)) genes causing Parkinson's disease (PD) are common in
Mediterranean populations. Variants in the Quinoid Dihydropteridine Reductase
NM_000320 (QDPR c.68G > A (p.G23D)), Sepiapterin Reductase NM_003124 (SPR c.596
2A > G) and Methylenetetrahydrofolate Reductase NM_005957 (MTHFR c.677C > T and
c.1298A > C) genes are frequent in Malta and potential candidates for PD.
METHODS: 178 cases and 402 control samples from Malta collected as part of the
Geoparkinson project were genotyped for MTHFR polymorphisms, QDPR and SPR
mutations. Only PD and parkinsonism cases were tested for SNCA and LRRK2
mutations. RESULTS: LRRK2 c.4321C > G and SNCA c.209G > A were not detected. The
LRRK2 c.6055G > A mutation was found in 3.1 % of Maltese PD cases. The QDPR
mutation was found in both cases and controls and did not increase risk for PD.
The SPR mutation was found in controls only. The odds ratios for MTHFR
polymorphisms were not elevated. CONCLUSIONS: The LRRK2 c.6055G > A is a cause of
PD in the Maltese, whilst QDPR c.68G > A, SPR c.596-2A > G and MTHFR c.677C > T
and c.1298A > C are not important determinants of PD.
PMID- 27613117
TI - Editorial Comment.
PMID- 27613118
TI - Editorial Comment.
PMID- 27613119
TI - Novel fMRI working memory paradigm accurately detects cognitive impairment in
multiple sclerosis.
AB - BACKGROUND: Cognitive impairment (CI) cannot be diagnosed by magnetic resonance
imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as
the immediate/delayed memory task (I/DMT), detect varying degrees of working
memory (WM). Preliminary findings using I/DMT showed differences in blood
oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and
non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. OBJECTIVES: The aim
of the study was to confirm CI detection based on I/DMT BOLD activation in a
larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded
Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought.
METHODS: A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m =
12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive
Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation
(WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on
MACFIMS. RESULTS: A total of 10 MSNI, 30 MSCI, and 4 borderline patients were
included in the analyses. Analysis of variance (ANOVA) showed MSNI had
significantly greater WMa than MSCI, in the left prefrontal cortex and left
supplementary motor area ( p = 0.032). Regression analysis showed significant
inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005,
0.004, respectively). CONCLUSION: I/DMT-based BOLD activation detects CI in MS.
Larger studies are needed to confirm these findings.
PMID- 27613120
TI - Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis
optica spectrum disorder.
AB - BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder
(NMOSD) are autoimmune inflammatory demyelinating diseases of the central nervous
system. Although distinguished by clinicoradiological and demographic features,
early manifestations can be similar complicating management. Antibodies against
aquaporin-4 support the diagnosis of NMOSD but are negative in some patients.
Therefore, there is unmet need for biomarkers that enable early diagnosis and
disease-specific intervention. OBJECTIVE: We investigated whether plasma
complement proteins are altered in MS and NMOSD and provide biomarkers that
distinguish these diseases. METHODS: Plasma from 54 NMOSD, 40 MS and 69 control
donors was tested in multiplex assays measuring complement activation products
and proteins. Using logistic regression, we tested whether combinations of
complement analytes distinguished NMOSD from controls and MS. RESULTS: All
activation products were elevated in NMOSD compared to either control or MS. Four
complement proteins (C1inh, C1s, C5 and FH) were higher in NMOSD compared to MS
or controls. A model comprising C1inh and terminal complement complex (TCC)
distinguished NMOSD from MS (area under the curve (AUC): 0.98), while C1inh and
C5 distinguished NMOSD from controls (AUC: 0.94). CONCLUSION: NMOSD is
distinguished from MS by plasma complement biomarkers. Selected complement
analytes enable differential diagnosis. Findings support trials of anti
complement therapies in NMOSD.
PMID- 27613121
TI - Decreased soluble IFN-beta receptor (sIFNAR2) in multiple sclerosis patients: A
potential serum diagnostic biomarker.
AB - BACKGROUND: The soluble isoform of the interferon-beta (IFN-beta) receptor
(sIFNAR2) could modulate the activity of both endogenous and systemically
administered IFN-beta. Previously, we described lower serum sIFNAR2 levels in
untreated multiple sclerosis (MS) than in healthy controls (HCs). OBJECTIVE: To
assess sIFNAR2 levels in a new cohort of MS patients and HCs, as well as in
patients with clinically isolated syndrome (CIS) and with other inflammatory
neurological disorders (OIND) and to assess its ability as a diagnostic
biomarker. METHODS: The cross-sectional study included 148 MS (84 treatment naive
and 64 treated), 87 CIS, 42 OIND, and 96 HCs. Longitudinal study included 94 MS
pretreatment and after 1 year of therapy with IFN-beta, glatiramer acetate (GA),
or natalizumab. sIFNAR2 serum levels were measured by a quantitative ELISA
developed and validated in our laboratory. RESULTS: Naive MS and CIS patients
showed significantly lower sIFNAR2 levels than HCs and OIND patients. The
sensitivity and specificity to discriminate between MS and OIND, for a sIFNAR2
cutoff value of 122.02 ng/mL, were 70.1%, and 79.4%, respectively. sIFNAR2
increased significantly in IFN-beta-treated patients during the first year of
therapy in contrast to GA- and natalizumab-treated patients who showed non
significant changes. CONCLUSION: The results suggest that sIFNAR2 could be a
potential diagnostic biomarker for MS.
PMID- 27613122
TI - CCL18 from ascites promotes ovarian cancer cell migration through proline-rich
tyrosine kinase 2 signaling.
AB - BACKGROUND: Ovarian cancer (OC) ascites consist in a proinflammatory tumor
environment that is characterized by the presence of various cytokines,
chemokines and growth factors. The presence of these inflammatory-related factors
in ascites is associated with a more aggressive tumor phenotype. CCL18 is a
member of CCL chemokines and its expression has been associated with poor
prognosis in some cancers. However, its role in OC progression has not been
established. Therefore, the aim of the current study was to elucidate the role of
ascites CCL18 in OC progression. METHODS: ELISA and tissue microarrays were used
to assess CCL18 in ascites and phospho-Pyk2 expression in cancer tissues
respectively. Cell migration was assessed using Boyden chambers. CCL18 and
ascites signaling was examined in ovarian cancer cells utilizing siRNA and
exogenous gene expression. RESULTS: Here, we show that CCL18 levels are markedly
increased in advanced serous OC ascites relative to peritoneal effusions from
women with benign conditions. Ascites and CCL18 dose-dependently enhanced the
migration of OC cell lines CaOV3 and OVCAR3. CCL18 levels in ascites positively
correlated with the ability of ascites to promote cell migration. CCL18 blocking
antibodies significantly attenuated ascites-induced cell migration. Ascites and
CCL18 stimulated the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) in
CaOV3 and OVCAR3 cells. Most importantly, the expression of phosphorylated Pyk2
in serous OC tumors was associated with shorter progression-free survival.
Furthermore, enforced expression of Pyk2 promoted tumor cell migration while
siRNA-mediated downregulation of Pyk2 attenuated cell migration. Downregulation
of Pyk2 markedly inhibited ascites and CCL18-induced cell migration. CONCLUSIONS:
Taken together, our findings establish an important role for CCL18, as a
component of ascites, in the migration of tumor cells and identify Pyk2 as
prognostic factor and a critical downstream signaling pathway for ascites-induced
OC cell migration.
PMID- 27613123
TI - Lymph node dissection improved survival in patients with metastatic thoracic
esophageal cancer: An analysis of 220 patients from the SEER database.
AB - BACKGROUND: To assess the clinical value of lymph node dissection and lymph node
status in patients with metastatic thoracic esophageal cancer (MTEC). METHODS:
The Surveillance Epidemiology and End Results (SEER) database was used to
identify patients with MTEC who had undergone esophagectomy from 2004 to 2012.
Kaplan-Meier survival analysis and Cox proportional hazard regression were used
to identify factors significantly associated with overall survival. RESULTS: A
total 220 eligible patients were identified, 162 (73.6%) of which underwent lymph
node dissection. The 1-year, 3-year, and 5-year overall survival rates were
55.0%, 17.9%, and 9.2%, respectively; the median survival time was 13 months.
Lymph node dissection was an independent prognostic factor of overall survival
(hazard ratio: 0.527, 95% confidence interval: 0.377-0.736, p < 0.001). Patients
who had undergone lymph node dissection had better overall survival than those
who did not (1-year, 62.8% vs. 33.7%; 3-year, 21.4% vs. 7.9%). In patients who
had undergone lymph node dissection, multivariate analysis determined that nodal
stage was an independent prognostic factor. However, the extent of lymph node
dissection was not associated with overall survival. CONCLUSIONS: Lymph node
dissection improves survival in patients with MTEC who undergo esophagectomy, and
the current lymph node staging can be used as a prognostic factor in patients
with MTEC.
PMID- 27613124
TI - Risk factors of post-operative delirium after elective vascular surgery in the
elderly: A systematic review.
AB - BACKGROUND: Postoperative delirium is a common and serious adverse event in the
elderly patient and is associated with significant morbidity and mortality. It is
of great importance to identify patients at risk for delirium, in order to focus
preventive strategies. The aim of this article is to systematically review
current available literature on pre-operative risk factors for delirium after
vascular surgery. METHODS: A systematic literature search was conducted using
PubMed and EMBASE, using the MeSH terms and key words "delirium", "surgery" and
"risk factor". Studies were retained for review after meeting strict inclusion
criteria that included only prospective studies evaluating risk factors for
delirium in patients who had elective vascular surgery. Diagnosis of delirium
needed to be confirmed using the Diagnostic and Statistical Manual of Mental
Disorders (DSM) or ICD-10. RESULTS: Fifteen articles were selected for inclusion,
incidence of delirium across the studies ranged from 5% to 39%. Many factors have
been associated with increased risk of delirium, including age, cognitive
impairment, comorbidity, depression, smoking, alcohol, visual and hearing
impairment, ASA-score, biochemical abnormalities, operative strategies and blood
loss. CONCLUSIONS: Delirium is a common complication after elective vascular
surgery in elderly. The highest delirium incidence was observed after open aortic
surgery as well as after surgery for critical limb ischemia. A picture starts to
form of which predisposing factors lead to increased risk of delirium. The
leading risk factors consistently identified in this systematic review were
advanced age and cognitive impairment. Multi-disciplinary specialist-led
interventions in the preoperative phase could decrease incidence and severity of
delirium and should be focused on identified high-risk patients.
PMID- 27613125
TI - The use of head-mounted display eyeglasses for teaching surgical skills: A
prospective randomised study.
AB - PURPOSE: To investigate whether 'surgeon's eye view' videos provided via head
mounted displays can improve skill acquisition and satisfaction in basic surgical
training compared with conventional wet-lab teaching. METHODS: A prospective
randomised study of 14 medical students with no prior suturing experience,
randomised to 3 groups: 1) conventional teaching; 2) head-mounted display
assisted teaching and 3) head-mounted display self-learning. All were instructed
in interrupted suturing followed by 15 minutes' practice. Head-mounted displays
provided a 'surgeon's eye view' video demonstrating the technique, available
during practice. Subsequently students undertook a practical assessment, where
suturing was videoed and graded by masked assessors using a 10-point surgical
skill score (1 = very poor technique, 10 = very good technique). Students
completed a questionnaire assessing confidence and satisfaction. RESULTS:
Suturing ability after teaching was similar between groups (P = 0.229, Kruskal
Wallis test). Median surgical skill scores were 7.5 (range 6-10), 6 (range 3-8)
and 7 (range 1-7) following head-mounted display-assisted teaching, conventional
teaching, and head-mounted display self-learning respectively. There was good
agreement between graders regarding surgical skill scores (rho.c = 0.599, r =
0.603), and no difference in number of sutures placed between groups (P = 0.120).
The head-mounted display-assisted teaching group reported greater enjoyment than
those attending conventional teaching (P = 0.033). Head-mounted display self
learning was regarded as least useful (7.4 vs 9.0 for conventional teaching, P =
0.021), but more enjoyable than conventional teaching (9.6 vs 8.0, P = 0.050).
CONCLUSIONS: Teaching augmented with head-mounted displays was significantly more
enjoyable than conventional teaching. Students undertaking self-directed learning
using head-mounted displays with pre-recorded videos had comparable skill
acquisition to those attending traditional wet-lab tutorials.
PMID- 27613126
TI - How could we identify the 'old' patient in gastric cancer surgery? A single
centre cohort study.
AB - PURPOSE: To analyze the population submitted to gastric cancer surgery in our
Institution in order to find those characteristics which could help in the
identification of the elderly high-risk patient. METHODS: In a cohort of 263
patients (>65 y) we selectively investigated the risk factors for medical and
surgical complications and postoperative mortality, focusing on the variable
"age". All the significant variables were used to find predictors of
complications with Clavien-Dindo>2. RESULTS: Age>75 (AUC 0.61; 95% 0.55-0.67, p =
0.003) and ASA score >2 (AUC 0.60; 95% CI 0.54-0.67, p = 0.01) were significantly
associated with an increased risk of medical complications. Operative time >330
min (OR 1.00; 95% CI 1.00-1.01; p = 0.0001- AUC 0.62, 95% CI 0.56-0.68, p = 0.01)
was the only significant predictor of surgical complications. In-hospital
mortality (6/263 patients) was significantly associated with preoperative albumin
<=2.95 g/dl (OR 0.15; 95% CI 0.04-0.93, p = 0.041 - AUC 0.74 95% CI 0.68-0.80; p
= 0.003) and additional procedures (OR 7.05; 1.23-40.32, p = 0.03). Stepwise
multivariate analysis showed that albumin <=2.95 g/dl (OR 3.43; 95% CI 1.06-11.13
p = 0.033), ASA>2 (OR 9.51; 95% CI 1.23-72.97; p = 0.042) and additional
resections (OR 3.39; 95% CI 1.36-8.45; p = 0.045) were independent risk factors
for complications Clavien Dindo >2. CONCLUSIONS: Our work demonstrated that, in
our institution, 75 years of age could identify the elderly in gastric surgery as
those patients were at higher risk of medical complications. ASA >2, preoperative
serum albumin <=2.95 g/dl and the need of additional procedures could increase
the risk of severe postoperative adverse events.
PMID- 27613127
TI - Comparison of three different methods for the quantification of equine insulin.
AB - BACKGROUND: Exact analysis of equine insulin in blood samples is the key element
for assessing insulin resistance or insulin dysregulation in horses. However,
previous studies indicated marked differences in insulin concentrations obtained
from sample analyses with different immunoassays. Most assays used in veterinary
medicine are originally designed for use in human diagnostics and are based on
antibodies directed against human insulin, although amino acid sequences between
equine and human insulin differ. Species-specific assays are being used more
frequently and seem to provide advantages compared to human-specific assays. The
aim of this study was to compare three immunoassays, one porcine-specific insulin
enzyme-linked immunosorbent assay (ELISA), advertised to be specific for equine
insulin, one porcine-specific insulin radioimmunoassay (RIA) and one human
specific insulin chemiluminescence immunoassay (CLIA), all three widely used in
veterinary laboratories for the analysis of equine insulin. Furthermore, we
tested their clinical applicability in assessing insulin resistance and
dysregulation by analysis of basal blood and blood samples obtained during a
dynamic diagnostic stimulation test (OGT) with elevated insulin concentrations.
RESULTS: Insulin values obtained from the ELISA, RIA and CLIA, investigated for
analyses of basal blood samples differed significantly between all three assays.
Analyses of samples obtained during dynamic diagnostic stimulation testing with
consecutively higher insulin concentrations revealed significantly (p < 0.001)
lower insulin concentrations supplied by the CLIA compared to the ELISA. However,
values measured by ELISA were intermediate and not different to those measured by
RIA. Calculated recovery upon dilution, as a marker for assay accuracy in diluted
samples, was 98 +/- 4 % for ELISA, 160 +/- 41 % for RIA and 101 +/- 11 % for
CLIA. CONCLUSIONS: Our results indicate that insulin concentrations of one sample
measured by different methods vary greatly and should be interpreted carefully.
Consideration of the immunoassay method and reliable assay-specific reference
ranges are of particular importance especially in clinical cases where small
changes in insulin levels can cause false classification in terms of insulin
sensitivity of horses and ponies.
PMID- 27613130
TI - Defining the Influence of Germline Variation on Metastasis Using Systems Genetics
Approaches.
AB - Cancer is estimated to be responsible for 8 million deaths worldwide and over
half a million deaths every year in the United States. The majority of cancer
related deaths in solid tumors is directly associated with the effects of
metastasis. While the influence of germline factors on cancer risk and
development has long been recognized, the contribution of hereditary variation to
tumor progression and metastasis has only gained acceptance more recently. A
variety of approaches have been used to define how hereditary variation
influences tumor progression and metastasis. One approach that garnered much
early attention was epidemiological studies of cohorts of cancer patients, which
demonstrated that specific loci within the human genome are associated with a
differential propensity for aggressive tumor development. However, a powerful,
and somewhat underutilized approach has been the use of systems genetics
approaches in transgenic mouse models of human cancer. Such approaches are
typically multifaceted, and involve integration of multiple lines of evidence
derived, for example, from genetic and transcriptomic screens of genetically
diverse mouse models of cancer, coupled with bioinformatics analysis of human
cancer datasets, and functional analysis of candidate genes. These methodologies
have allowed for the identification of multiple hereditary metastasis
susceptibility genes, with wide-ranging cellular functions including regulation
of gene transcription, cell proliferation, and cell-cell adhesion. In this
chapter, we review how each of these approaches have facilitated the
identification of these hereditary metastasis modifiers, the molecular functions
of these metastasis-associated genes, and the implications of these findings upon
patient survival.
PMID- 27613129
TI - The Relationship Between Dormant Cancer Cells and Their Microenvironment.
AB - The majority of cancer deaths are due to metastases that can occur years or
decades after primary tumor diagnosis and treatment. Disseminated tumor cells
(DTCs) surviving in a dormant state in target organs appear to explain the timing
of this phenomenon. Knowledge on this process is important as it might provide a
window of opportunity to prevent recurrences by eradicating dormant DTCs and/or
by maintaining DTCs in a dormant state. Importantly, this research might offer
markers of dormancy for early monitoring of metastatic relapse. However, our
understanding of the mechanisms underlying the regulation of entry into and exit
from dormancy is still limited and crippling any therapeutic opportunity. While
cancer cell-intrinsic signaling pathways have been linked to dormancy regulation,
it is likely that these pathways and the switch controlling reactivation from
dormancy are regulated by microenvironmental cues. Here we review and discuss
recent findings on how the microenvironment regulates cancer dormancy and raise
new questions that may help advance the field.
PMID- 27613131
TI - Breast Cancer Metastasis Suppressor 1 (BRMS1): Robust Biological and Pathological
Data, But Still Enigmatic Mechanism of Action.
AB - Metastasis requires coordinated expression of multiple genetic cassettes, often
via epigenetic regulation of gene transcription. BRMS1 blocks metastasis, but not
orthotopic tumor growth in multiple tumor types, presumably via SIN3 chromatin
remodeling complexes. Although there is an abundance of strong data supporting
BRMS1 as a metastasis suppressor, the mechanistic data directly connecting
molecular pathways with inhibition of particular steps in metastasis are not well
defined. In this review, the data for BRMS1-mediated metastasis suppression in
multiple tumor types are discussed along with the steps in metastasis that are
inhibited.
PMID- 27613133
TI - MicroRNA and Metastasis.
AB - Noncoding RNAs are important regulatory molecules of cellular processes.
MicroRNAs (miRNAs) are small noncoding RNAs that bind to complementary sequences
in the 3' untranslated region of target mRNAs, leading to degradation of the
target mRNAs and/or inhibition of their translation. Some miRNAs are essential
for normal animal development; however, many other miRNAs are dispensable for
development but play a critical role in pathological conditions, including
tumorigenesis and metastasis. miRNA genes often reside at fragile chromosome
sites and are deregulated in cancer. Some miRNAs function as oncogenes or tumor
suppressors, collectively termed "oncomirs." Specific metastasis-regulating
miRNAs, collectively termed "metastamirs," govern molecular processes and
pathways in malignant progression in either a tumor cell-autonomous or a cell
nonautonomous manner. Recently, exosome-transferred miRNAs have emerged as
mediators of the tumor-stroma cross talk. In this chapter, we focus on the
functions, mechanisms of action, and therapeutic potential of miRNAs,
particularly oncomirs and metastamirs.
PMID- 27613134
TI - Plasticity of Cancer Cell Invasion-Mechanisms and Implications for Therapy.
AB - Cancer cell migration is a plastic and adaptive process integrating cytoskeletal
dynamics, cell-extracellular matrix and cell-cell adhesion, as well as tissue
remodeling. In response to molecular and physical microenvironmental cues during
metastatic dissemination, cancer cells exploit a versatile repertoire of invasion
and dissemination strategies, including collective and single-cell migration
programs. This diversity generates molecular and physical heterogeneity of
migration mechanisms and metastatic routes, and provides a basis for adaptation
in response to microenvironmental and therapeutic challenge. We here summarize
how cytoskeletal dynamics, protease systems, cell-matrix and cell-cell adhesion
pathways control cancer cell invasion programs, and how reciprocal interaction of
tumor cells with the microenvironment contributes to plasticity of invasion and
dissemination strategies. We discuss the potential and future implications of
predicted "antimigration" therapies that target cytoskeletal dynamics, adhesion,
and protease systems to interfere with metastatic dissemination, and the options
for integrating antimigration therapy into the spectrum of targeted molecular
therapies.
PMID- 27613135
TI - Cytokine Regulation of Metastasis and Tumorigenicity.
AB - The human body combats infection and promotes wound healing through the
remarkable process of inflammation. Inflammation is characterized by the
recruitment of stromal cell activity including recruitment of immune cells and
induction of angiogenesis. These cellular processes are regulated by a class of
soluble molecules called cytokines. Based on function, cell target, and
structure, cytokines are subdivided into several classes including: interleukins,
chemokines, and lymphokines. While cytokines regulate normal physiological
processes, chronic deregulation of cytokine expression and activity contributes
to cancer in many ways. Gene polymorphisms of all types of cytokines are
associated with risk of disease development. Deregulation RNA and protein
expression of interleukins, chemokines, and lymphokines have been detected in
many solid tumors and hematopoetic malignancies, correlating with poor patient
prognosis. The current body of literature suggests that in some tumor types,
interleukins and chemokines work against the human body by signaling to cancer
cells and remodeling the local microenvironment to support the growth, survival,
and invasion of primary tumors and enhance metastatic colonization. Some
lymphokines are downregulated to suppress tumor progression by enhancing
cytotoxic T cell activity and inhibiting tumor cell survival. In this review, we
will describe the structure/function of several cytokine families and review our
current understanding on the roles and mechanisms of cytokines in tumor
progression. In addition, we will also discuss strategies for exploiting the
expression and activity of cytokines in therapeutic intervention.
PMID- 27613136
TI - Preface.
PMID- 27613128
TI - Detecting Tumor Metastases: The Road to Therapy Starts Here.
AB - Metastasis is the complex process by which primary tumor cells migrate and
establish secondary tumors in an adjacent or distant location in the body. Early
detection of metastatic disease and effective therapeutic options for targeting
these detected metastases remain impediments to effectively treating patients
with advanced cancers. If metastatic lesions are identified early, patients might
maximally benefit from effective early therapeutic interventions. Further,
monitoring patients whose primary tumors are effectively treated for potential
metastatic disease onset is also highly valuable. Finally, patients with
metastatic disease can be monitored for efficacy of specific therapeutic
interventions through effective metastatic detection techniques. Thus, being able
to detect and visualize metastatic lesions is key and provides potential to
greatly improve overall patient outcomes. In order to achieve these objectives,
researchers have endeavored to mechanistically define the steps involved in the
metastatic process as well as ways to effectively detect metastatic progression.
We presently overview various preclinical and clinical in vitro and in vivo
assays developed to more efficiently detect tumor metastases, which provides the
foundation for developing more effective therapies for this invariably fatal
component of the cancerous process.
PMID- 27613137
TI - Influence of inferior border cut on lingual fracture pattern during bilateral
sagittal split osteotomy with splitter and separators: A prospective
observational study.
AB - Bilateral sagittal split osteotomy (BSSO) is a widely used orthognathic surgery
technique. This prospective observational study investigated the correspondence
between the planned inferior border cut and the actually executed inferior border
cut during BSSO. The influence of the inferior border cut on lingual fracture
patterns was also analyzed. Postoperative cone beam computed tomography (CBCT)
scans of 41 patients, representing 82 sagittal split osteotomies, were
investigated. The inferior border cut was intended to penetrate completely
through the caudal cortex. Descriptive statistics were used to analyze the
executed inferior border cuts. Mixed models were used to investigate the
influence of independent variables such as the surgeon's experience on the
inferior border cut. Secondarily the influence of the inferior border cut on
lingual fracture patterns and the incidence of bad splits was assessed. The
inferior border cut reached the caudal cortex in all cases, but reached the
lingual cortex in only 38% of the splits. There was no significant relationship
between the inferior border cut and a specific lingual fracture line. In this
study, postoperative CBCT analysis revealed that the bone cuts during BSSO were
often not placed exactly as planned. No significant relationship between the
inferior border cut and lingual fracture patterns or bad splits was, however,
detected.
PMID- 27613132
TI - Immune Regulation of the Metastatic Process: Implications for Therapy.
AB - Metastatic disease is the major cause of fatalities in cancer patients, but few
therapies are designed to target the metastatic process. Cancer cells must
perform a number of steps to successfully establish metastatic foci, including
local invasion, intravasation, survival, extravasation, and growth in ectopic
tissue. Due to the nonrandom distribution of metastasis, it has long been
recognized that the tissue microenvironment must be an important determinant of
colonization. More recently it has been established in animal models that immune
cells regulate the metastatic process, including a dominant role for monocytes
and macrophages, and emerging roles for neutrophils and various lymphocyte
populations. While most research has focused on the early dissemination process,
patients usually present clinically with disseminated, if not macroscopic,
disease. Identifying pathways by which immune cells regulate growth and
therapeutic resistance within metastatic sites is therefore key to the
development of pharmacological agents that will significantly extend patient
survival.
PMID- 27613138
TI - "IIb or not IIb" - The necessity of dissection in patients with oral squamous
cell carcinoma.
AB - The necessary extent of cervical dissection in oral squamous cell carcinoma
(OSCC) is still under discussion. Due to its anatomical properties Robins level
IIb has a special role in neck dissection. This study focuses on the lymph node
metastatic behaviour of OSCC in level IIb and evaluates its worth of dissection.
183 consecutive patients with OSCC were retrospectively screened for age, gender,
TNM classification, cancer stage (after UICC), tumour localization, tumour
infiltrations depth, and affected cervical lymph node levels. Associations
between lymph node metastases and the above-mentioned characteristics were
evaluated using Pearson's chi square test and Spearman's rho correlation
analyses. Metastases in level IIb were seen in only 3.3% of all patients, and
none of these metastases were an exclusive metastasis. Lymph node metastases most
likely occurred in levels I and IIa at ipsilateral sites, and metastases were
significantly related to tumour size (p < 0.01) and the infiltration of lymph
vessels (p < 0.001). The locations of primary cancer sites in metastatic disease
were the soft palate, alveolar crest of the lower jaw and buccal mucosa. Lymph
node metastases of OSCC in level IIb remain rare, especially as exclusive
metastases and in clinically N-negative necks. The findings of our study support
the hypothesis of sparing neck dissection in level IIb in cases of clinically
negative necks.
PMID- 27613139
TI - Expression of type III interferons (IFNlambdas) and their receptor in Sjogren's
syndrome.
AB - Type III interferons (IFNs) or IFN-lambdas (IFN-lambda1/IL29, IFN
lambda2/interleukin (IL)-28A and IFN-lambda3/IL-28B) consist of a recently
identified group of IFNs, implicated initially in several human diseases,
including cancer and autoimmunity. In this study, we sought to investigate the
expression of type III IFNs and their common receptor IFN-lambdaR1/IL-28Ra in
Sjogren's syndrome (SS). Type III IFN expression was examined in minor salivary
gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting
or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC)
from SS patients and sicca-complaining controls. All type III IFN family members
were detected in ductal and acinar epithelia of MSGs from both SS patients and
sicca controls. IFN-lambda2/IL-28A and IFN-lambda3/IL-28B were also expressed in
infiltrating mononuclear cells. In SS patients with intermediate MSG lesions, the
epithelial expression of IFN-lambda2/IL-28A was more intense compared to sicca
controls (P < 0.05). The receptor IFN-lambdaR1/IL-28Ra was detected in all types
of cells except fibroblasts, and was exceptionally strong in plasmatocytoid
dendritic cells, indicating that they are susceptible to type III IFN-mediated
regulation. In the periphery, only IFN-lambda1/IL-29 was detected in the sera and
was elevated significantly in SS patients with intermediate MSG inflammatory
lesions compared to sicca controls (P = 0.0053). None of the type III IFNs was
expressed constitutively in resting SGECs; they were all induced readily by TLR-3
stimulation, suggesting that the in-situ epithelial expression can be attributed
to local microenvironment. Type III IFNs are expressed in MSGs in a similar
pattern to type I IFNs and their expression is probably subjected to micro
environmental regulation, suggesting that they are implicated in the inflammatory
processes occurring in the affected exocrine glands.
PMID- 27613140
TI - MiR-26a inhibits proliferation and migration of HaCaT keratinocytes through
regulating PTEN expression.
AB - MicroRNAs (miRNAs) have been shown to be associated with differentiation,
migration and apoptosis in keratinocyte. Although it has been reported that
microRNA-26a (miR-26a) plays important roles in tumor cells, its biological
functions in keratinocytes are still not well elucidated. In this study, we
confirmed expression of miR-26a in human keratinocytes using RT-PCR and further
studied the role of miR-26a in cell proliferation and cell migration. Ectopic
expression of MiR-26a mimic or inhibitor increased or decreased miR-26a
expression respectively in HaCaT cells. Proliferation of HaCaT keratinocyte can
be suppressed or promoted by overexpression or down-expression of miR-26a. In
scratch wound-healing assay and Boyden chamber cell migration assay, upregulating
miR-26a expression blocked cell migration, while downregulating miR-26a
expression enhanced the migration. Using quantitative RT-PCR (qRT-PCR) and
western blot, we further discovered that both mRNA and protein level of
phosphatase and tensin homolog deleted from chromosome 10(PTEN) were regulated by
miR-26a in HaCaT cells. Meanwhile the level of active form of AKT was also
regulated by the miR-26a. In rescue experiment, knockdown of PTEN in the miR-26a
mimic transduced cells recovered the migration ability of HaCaT cells. Together
these results suggest that miR-26a modulates the proliferation and migration of
keratinocytes via regulating PTEN/AKT signaling pathway.
PMID- 27613141
TI - Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of
blood flow.
AB - Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can
produce similar effects upon muscles to that of high-intensity resistance
training (HIRT) while overcoming many of the restrictions to HIRT that occurs in
a clinical setting. However, the potential molecular mechanisms of BFR induced
muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to
better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR
and reveal possible clinical therapeutic targets for atrophy cases. We performed
genome wide screening with microarray analysis to identify unique differentially
expressed genes during rat muscle hypertrophy. We then successfully separated the
differentially expressed genes from BRF treated soleus samples by comparing the
Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and
immunohistochemistry (IHC) we also analyzed other related differentially
expressed genes. Results suggested that muscle hypertrophy induced by BFR is
essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and
MAPK pathways act as positive regulators in controlling protein synthesis where
ubiquitin-proteasome acts as a negative regulator. This represents the first
general genome wide level investigation of the gene expression profile in the rat
soleus after BFR treatment. This may aid our understanding of the molecular
mechanisms regulating and controlling muscle hypertrophy and provide support to
the BFR strategies aiming to prevent muscle atrophy in a clinical setting.
PMID- 27613142
TI - Proximity of AUG sequences to initiation codon in genomic 5' UTR regulates
mammalian protein expression.
AB - Protein expression can be controlled via AUG sequences located upstream to the
initiation codon in the 5' end untranslated region (5' UTR). Our study was
focused on the effect of distance between the initiation codon and the first
upstream AUG. An inhibitory effect on protein expression was established when AUG
exists in 5' UTR, and this effect is increased when multiple AUG sequences occur
there. The study was performed with ATG16L2, a non-lethal gene with no introns or
upstream AUG sequence to avoid any interference. New mutations were generated at
different locations within the promoter region of ATG16L2 gene and added to a
plasmid construct containing a luciferase gene reporter gene. The results show a
clear relationship between the distance of the novel AUGs from initiation codon
and protein expression. The inhibitory effect was even stronger when multiple AUG
sequences were present in 5' UTR.
PMID- 27613143
TI - A novel exon generates ubiquitously expressed alternatively spliced new
transcript of mouse Abcc4 gene.
AB - Abcc4 gene codes for a protein (ABCC4) involved in the transportation of
different classes of drugs outside the cells. Various important drugs transported
by ABCC4 include antiviral and anticancer drugs as well as endogenous molecules
such as bile acids, cyclic nucleotides, folates, prostaglandins and steroids.
Alternative splicing generates multiple mRNAs that encode protein isoforms having
diverse functions. In this study, we have identified a novel transcript of mouse
Abcc4 gene using a combination of bioinformatics and molecular biology
techniques. This transcript was found to be different from the reported
transcript in having a different first exon that was found to be located on
previously identified first intron. Newly identified transcript was found to be
expressed across different tissues we studied and in different developmental
stages. Expression level of novel and reported transcripts was studied using
quantitative real-time PCR. After conceptually translating the novel transcript,
various post-translational modifications were studied. Translation efficiency and
predicted half life of encoded protein isoforms were analysed in silico.
Molecular modelling was performed to compare the structural differences in both
isoforms. The diversity at N-termini in these protein isoforms explains the
diverse function of ABCC4 in mouse.
PMID- 27613144
TI - A new LDLa domain-containing C-type lectin with bacterial agglutinating and
binding activity in amphioxus.
AB - Over 1200 C-type lectin gene models have been identified in amphioxus, but only a
few of them have been functionally characterized. In this study, we identified a
C-type lectin, BjCTL, with domain structure of LDLa-CTLD-EGF_Lam, the first such
data in chordates. It was expressed mainly in the notochord and ovary in a tissue
dependent fashion. Recombinant BjCTL was characterized as a typical Ca2+
dependent carbohydrate-binding protein capable of agglutinating and binding to
both Gram-negative and positive bacteria we tested. In addition, it specifically
bound to insoluble lipopolysaccharide, lipoteichoic acid and peptidoglycan, which
can be inhibited by galactose. We also showed that the interaction of BjCTL with
the bacteria is primarily attributable to CTLD domain. Thus, BjCTL is a novel
pattern recognition protein involved in lectin-mediated innate immunity.
PMID- 27613145
TI - Separation of monoclonal antibody charge state variants by open tubular capillary
electrochromatography with immobilised protein as stationary phase.
AB - Monoclonal antibodies (mAbs) are highly heterogeneous and complex glycoproteins
requiring powerful analytical tools for characterization and quality control. In
this work, we utilize adsorbed bovine serum albumin (BSA) as a stationary phase
in open tubular (OT) capillary electrochromatography for separation of charge
state variants of mAbs. Poly(diallydimethylammonium chloride) (PDDA) was used to
assist fabrication of BSA coated OT column by electrostatic self-assembly.
Scanning electron microscopy and electroosmotic flow measurement were carried out
to characterize the as-prepared BSA coated PDDA OT columns. The
electrochromatographic performance of the OT columns was evaluated by separation
of basic proteins and different charge state variants of mAbs. The effects of
background solution pH and concentration on separation were investigated. A rapid
separation of charge state variants of mAbs was successfully achieved in the BSA
coated PDDA OT column. Separation of seven variants of the mAb cetuximab was
achieved using the prepared column. Two basic variants and one acidic variant of
rituximab, and two basic variants and four acidic variants of trastuximab were
successfully distinguished from the main forms. In addition, the columns
demonstrated good repeatability and stability with the run-to-run, day-to-day and
batch-to-batch relative standard deviations of migration times less than 3.7%.
PMID- 27613146
TI - Interface-free capillary electrophoresis-mass spectrometry system with nanospray
ionization-Analysis of dexrazoxane in blood plasma.
AB - The newly developed interface-free capillary electrophoresis-nanospray/mass
spectrometry system (CE-nESI/MS) was applied for rapid analysis of the
cardioprotective drug dexrazoxane and its hydrolysed form ADR-925 in
deproteinized blood plasma samples. The aim of this study was to test the
simplest possible CE-nESI/MS instrumentation for analyses of real samples. This
interface-free system, utilizing single piece of a narrow bore capillary as both
the electrophoretic separation column and the nanospray emitter, was operated at
a flow rate of 30nL/min. Excellent electrophoretic separation and sensitive
nanospray ionization was achieved with the use of only one high voltage power
supply. In addition, hydrophobic external coating was developed and tested for
additional stability of the nanospray ionization. To our knowledge this is the
first study devoted to the analysis of dexrazoxane and ADR-925 by capillary
electrophoresis-mass spectrometry.
PMID- 27613147
TI - Preparation of an adsorbent based on polymeric ionic liquid for the simultaneous
extraction of acidic, basic and neutral pollutants.
AB - In this study, coextraction of acidic, basic and neutral pollutants was realized
with a new adsorbent based on polymeric ionic liquid (PIL). In the presence of a
porogen solvent containing 1-propanol and 1,4-butanediol, an ionic liquid, 1
vinyl-3-octylimidazolium tetrafluoraborate was used as monomer to copolymerize
with dual cross-linkers (divinylbenzene and N,N-methylene-bisacrylamide) to form
the adsorbent for stir cake sorptive extraction (SCSE). Phenols, aromatic amines
and parabens were selected as acidic, basic and neutral model analytes,
respectively. The effects of preparation conditions and extraction parameters on
the extraction performance of SCSE/PIL were investigated thoroughly. Under the
optimized conditions, the prepared adsorbent showed satisfactory coextraction
performance to the selected analytes with multiply interactions. At the same
time, simple and sensitive analytical method for simultaneous determination of
phenols, aromatic amines and parabens in environmental water samples was
developed by the combination of SCSE/PIL with high-performance liquid
chromatography with diode array detection. Low limits of detection (S/N=3) and
quantification limits (S/N=10) of the proposed method for the targeted analytes
were achieved within the range of 0.064-0.30MUg/L and 0.21-0.99MUg/L,
respectively. The precision of the proposed method was evaluated in terms of
intra- and inter-assay variability calculated as relative standard deviation
(RSD), and it was found that the RSD values were all below 10%. Ultimately, the
applicability of developed method was successfully confirmed by analyzing lake,
reservoir and river water samples. Recoveries obtained for the determination of
targeted analytes in spiking samples ranged from 70.0% to 112%, with RSDs within
the range of 1.6-9.8%.
PMID- 27613148
TI - Gene expression profiling of calcium-channel antagonists in the heart of
hypertensive and normotensive rats reveals class specific effects.
AB - Calcium channel blockers (CCB) differ in their effects on the cardiovascular
system with diltiazem being less negatively ionotrop as compared to verapamil.
Diltiazem is mainly used to treat supraventricular tachycardia, vasospastic
angina and the Raynaud's syndrome. Little is known about the molecular effects of
benzothiazepins on cardiac gene expression. We therefore investigated the effects
of diltiazem on cardiac gene expression in normotensive and hypertensive rats
with left ventricular hypertrophy and compared the results with our previous
findings on verapamil and nifedipine. Spontaneously hypertensive (SHR) and
normotensive Sprague Dawley (SD) rats were treated with 15mg/kg diltiazem b.i.d.
for 3days. Total RNA was isolated from surgically removed hearts and the gene
expression of ion channels, ion transporters and their associated partners,
calcium handling proteins as well as stress and cellular differentiation markers
was investigated by RT-PCR. Subsequently, hierarchical gene cluster analysis was
performed to decode treatment effects of different classes of CCBs. CCB treatment
of normotensive and hypertensive rats revealed class specific effects with
diltiazem specifically repressing cardiac genes pertinent for ion homeostasis and
excitation-contraction coupling in normotensive but not hypertensive rats.
Conversely, verapamil and nifedipine caused predominantly repression of genes to
affect ion homeostasis and contractile dysfunction in spontaneously hypertensive
rats; nonetheless, genes coding for calcium-handling proteins were up-regulated.
Unlike diltiazem treatment of normotensive rats with verapamil and/or nifedipine
did not influence cardiac gene expression. The effects of diltiazem on cardiac
gene expression provide a molecular rationale for its use in the treatment of
vasospastic angina.
PMID- 27613150
TI - Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and
Addiction Treatment Providers in the Netherlands.
AB - BACKGROUND: Extended-release naltrexone (XRNT) was developed to overcome poor
treatment compliance with oral naltrexone in alcohol and opioid-dependent
patients. XRNT injections are registered in the United States and Russia, but not
in The Netherlands. However, XRNT can be obtained for individual patients, but it
is expensive and not reimbursed by the health insurance. OBJECTIVES: This study
evaluates the support for abstinence oriented treatment among heroin-dependent
patients and the acceptability of XRNT injections by heroin-dependent patients
and treatment providers in The Netherlands. METHODS: A sample of 261 patients in
methadone maintenance treatment or heroin assisted treatment and a sample of 188
addiction treatment providers completed specially designed questionnaires.
RESULTS: The current study shows that many patients in opioid maintenance
treatment (58%) report a desire to become abstinent from opioids and that 83% of
the patients with a desire for abstinence are interested in XRNT. The majority of
treatment providers (81%) are willing to support the prescription of XRNT
injections in opioid-dependent patients to prevent relapse after detoxification.
CONCLUSIONS: The current practice of automatic and indefinite continuation of
opioid substitution should therefore be reconsidered. However, XRNT injections
are very expensive and currently not reimbursed by the health insurance agencies
in The Netherlands and thus not really available to most patients.
PMID- 27613149
TI - Rubella persistence in epidermal keratinocytes and granuloma M2 macrophages in
patients with primary immunodeficiencies.
PMID- 27613152
TI - Correspondence on review article published in Oral Oncology (Vol. 59, August
2016): "Evaluation of the benefit and use of multidisciplinary teams in the
treatment of head and neck cancer."
PMID- 27613151
TI - Treatment for unstable slipped capital femoral epiphysis: Current status and
future challenge in Japan.
AB - BACKGROUND: Treatment for unstable slipped capital femoral epiphysis (SCFE) is
challenging and controversial. For many years, the debate centered around closed
treatments and especially the pros and cons of manual reduction and its concrete
procedure. However, recent studies reported on open treatments such as open
reduction through an anterior approach and modified Dunn procedure. Being in a
period of such transition, we investigated the current status and future
challenge of treatment for unstable SCFE. METHODS: A questionnaire survey of
medical institutions specializing in pediatric hip disorders across Japan was
conducted. Survey items were the accurate diagnosis of physeal stability, the pre
and intra-operative evaluation of epiphyseal hemodynamics, and current treatment
strategy. RESULTS: Survey responses returned from 29 out of 40 participant
institutions (response rate: 73%) revealed that 55% of the institutions evaluated
physeal stability based on clinical findings of ambulation capability in
accordance with the Loder classification. Another 38% diagnosed physeal stability
comprehensively by combining the Loder classification and imaging findings.
Epiphyseal hemodynamics was assessed preoperatively in 18% of the institutions,
effectively using angiography, contrast-enhanced magnetic resonance imaging
(MRI), and bone scintigraphy. Intraoperative assessment was performed in 13%
based on the bleeding through a drilling hole on the articular surface and
observation of the cancellous bone color during open surgeries. As a treatment
strategy, 52% of the institutions used in-situ fixation, while another 38% used
manual reduction and internal fixation. On the other hand, open reduction was
used at 3 institutions (the remaining 10%): the modified Dunn procedure at 2
institutions and arthrotomy at 1 institution. CONCLUSION: Treatment for unstable
SCFE remains controversial, but closed treatments without hemodynamic monitoring
is no longer the center of the controversy. Today, the topic of the discussion is
shifting toward how to correlate hemodynamic findings with treatment procedures
and the indications for open treatments.
PMID- 27613153
TI - A simple method to determine IgG light chain to heavy chain polypeptide ratios
expressed by CHO cells.
AB - OBJECTIVES: To establish a high-throughput method for determination of antibodies
intra- and extracellular light chain (LC) to heavy chain (HC) polypeptide ratio
as screening parameter during cell line development. RESULTS: Chinese Hamster
Ovary (CHO) TurboCell pools containing different designed vectors supposed to
result in different LC:HC polypeptide ratios were generated by targeted
integration. Cell culture supernatants and cell lysates of a fed batch experiment
were purified by combined Protein A and anti-kappa affinity batch purification in
96-well format. Capture of all antibodies and their fragments allowed the
determination of the intra- and extracellular LC:HC peptide ratios by reduced SDS
capillary electrophoresis. Results demonstrate that the method is suitable to
show the significant impact of the vector design on the intra- and extracellular
LC:HC polypeptide ratios. CONCLUSION: Determination of LC:HC polypeptide ratios
can give important information in vector design optimization leading to CHO cell
lines with optimized antibody assembly and preferred product quality.
PMID- 27613154
TI - Codon optimization of Saccharomyces cerevisiae mating factor alpha prepro-leader
to improve recombinant protein production in Pichia pastoris.
AB - OBJECTIVES: To evaluate different codon optimization parameters on the
Saccharomyces cerevisiae-derived mating factor alpha prepro-leader sequence
(MFLS) to improve Candida antarctica lipase B (CAL-B) secretory production in
Pichia pastoris. RESULTS: Codon optimization based on the individual codon usage
(ICU) and codon context (CC) design parameters enhanced secretory production of
CAL-B to 7 U/ml and 12 U/ml, respectively. Only 3 U/ml was obtained with the wild
type sequence while the sequence optimized using both ICU and CC objectives
showed intermediate performance of 10 U/ml. These results clearly show that CC is
the most relevant parameter for the codon optimization of MFLS in P. pastoris,
and there is no synergistic effect achieved by considering both ICU and CC
together. CONCLUSION: The CC optimized MFLS increased secretory protein
production of CAL-B in P. pastoris by fourfold.
PMID- 27613156
TI - Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial
dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC
1alpha pathway.
AB - Vasculopathy is a major complication of diabetes. Impaired mitochondrial
bioenergetics and biogenesis due to oxidative stress are a critical causal factor
for diabetic endothelial dysfunction. Sirt1, an NAD+-dependent enzyme, is known
to play an important protective role through deacetylation of many substrates
involved in oxidative phosphorylation and reactive oxygen species generation.
Mesenchymal stem cell-conditioned medium (MSC-CM) has emerged as a promising cell
free therapy due to the trophic actions of mesenchymal stem cell (MSC)-secreted
molecules. In the present study, we investigated the therapeutic potential of MSC
CMs in diabetic endothelial dysfunction, focusing on the Sirt1 signalling pathway
and the relevance to mitochondrial function. We found that high glucose
stimulated MSC-CM attenuated several glucotoxicity-induced processes, oxidative
stress and apoptosis of endothelial cells of the human umbilical vein. MSC-CM
perfusion in diabetic rats ameliorated compromised aortic vasodilatation and
alleviated oxidative stress in aortas. We further demonstrated that these effects
were dependent on improved mitochondrial function and up-regulation of Sirt1
expression. MSC-CMs activated the phosphorylation of phosphoinositide 3-kinase
(PI3K) and protein kinase B (Akt), leading to direct interaction between Akt and
Sirt1, and subsequently enhanced Sirt1 expression. In addition, both MSC-CM and
Sirt1 activation could increase the expression of peroxisome proliferator
activated receptor gamma co-activator-1alpha (PGC-1alpha), as well as increase
the mRNA expression of its downstream, mitochondrial, biogenesis-related genes.
This indirect regulation was mediated by activation of AMP-activated protein
kinase (AMPK). Overall our findings indicated that MSC-CM had protective effects
on endothelial cells, with respect to glucotoxicity, by ameliorating
mitochondrial dysfunction via the PI3K/Akt/Sirt1 pathway, and Sirt1 potentiated
mitochondrial biogenesis, through the Sirt1/AMPK/PGC-1alpha pathway.
PMID- 27613157
TI - Identification of genetic defects in pulmonary arterial hypertension by a new
gene panel diagnostic tool.
AB - In the present study we developed a new specific gene panel for pulmonary
arterial hypertension (PAH) including major disease genes and further candidates.
We assessed 37 patients with invasively confirmed PAH and five relatives of
affected patients for genetic testing. A new PAH-specific gene panel was designed
using next generation sequencing (NGS) including 12 known disease genes and 17
further candidates. Any potential pathogenic variants were reassessed by Sanger
sequencing. Twenty-two of the 37 patients (59%) had a mutation in BMPR2, ALK1,
ENG or EIF2AK4 genes identified by panel and Sanger sequencing. In addition, 12
unclassified variants were identified in seven genes (known and candidate genes).
A sensitivity of 100% was met after quality parameters were adjusted. Specificity
increased to 100% when Sanger technique was added as a routine validation. The
new PAH-specific gene panel developed in the present study allowed for the first
time the assessment of all known PAH genes and further candidates at once and
markedly reduced overall sequencing time and costs. Sensitivity and specificity
reached 100% when Sanger sequencing was additionally applied. Thus, this
technique will potentially change the routine diagnostic genetic testing in PAH
patients.
PMID- 27613158
TI - APOA5 genetic and epigenetic variability jointly regulate circulating
triacylglycerol levels.
AB - Apolipoprotein A5 gene (APOA5) variability explains part of the individual's
predisposition to hypertriacylglycerolaemia (HTG). Such predisposition has an
inherited component (polymorphisms) and an acquired component regulated by the
environment (epigenetic modifications). We hypothesize that the integrated
analysis of both components will improve our capacity to estimate APOA5
contribution to HTG. We followed a recruit-by-genotype strategy to study a
population composed of 44 individuals with high cardiovascular disease risk
selected as being carriers of at least one APOA5 SNP (-1131T>C and/or, S19W
and/or 724C>G) compared against 34 individuals wild-type (WT) for these SNPs. DNA
methylation patterns of three APOA5 regions [promoter, exon 2 and CpG island
(CGI) in exon 3] were evaluated using pyrosequencing technology. Carriers of
APOA5 SNPs had an average of 57.5% higher circulating triacylglycerol (TG) levels
(P=0.039). APOA5 promoter and exon 3 were hypermethylated whereas exon 2 was
hypomethylated. Exon 3 methylation positively correlated with TG concentration
(r=0.359, P=0.003) and with a lipoprotein profile associated with atherogenic
dyslipidaemia. The highest TG concentrations were found in carriers of at least
one SNP and with a methylation percentage in exon 3 >=82% (P=0.009). In
conclusion, CGI methylation in exon 3 of APOA5 acts, in combination with
1131T>C, S19W and 724C>G polymorphisms, in the individual's predisposition to
high circulating TG levels. This serves as an example that combined analysis of
SNPs and methylation applied to a larger set of genes would improve our
understanding of predisposition to HTG.
PMID- 27613159
TI - From Good to Better: New Dutch Guidelines for Economic Evaluations in Healthcare.
PMID- 27613160
TI - 'Under pressure': is there a link between orthostatic hypotension and cognitive
impairment in alpha-synucleinopathies?
AB - Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are
characterised by abnormal neuroglial alpha-synuclein accumulation. These alpha
synucleinopathies have in common parkinsonism and non-motor features including
orthostatic hypotension (OH) and cognitive impairment. However, the nature of the
relationship between OH and cognitive impairment is unclear. We therefore
systematically reviewed the literature for evidence of an association between OH
and cognitive impairment in alpha-synucleinopathies and discuss possible
mechanisms and implications of this relationship. Abstracts from 313 original
research articles were surveyed, and a total of 132 articles were considered for
this review. Articles were stratified as: 'direct-evidence studies' based on the
direct assessment for a relationship between OH and cognitive impairment in alpha
synucleinopathies, and 'indirect-evidence studies' based on an association being
referred to as a secondary outcome. Ten 'direct-evidence papers' were identified,
seven of which reported a positive association between OH and cognitive
impairment, while seven of 12 'indirect-evidence papers' similarly did as well.
The papers that reported no association between OH and cognitive impairment used
less sensitive measures of cognition. A relationship between OH and cognitive
impairment in patients with alpha-synucleinopathies exists, but the underlying
mechanisms remain unclear. Three hypotheses are proposed: (1) OH and cognitive
impairment occur concurrently due to diffuse brain and peripheral deposition of
alpha-synuclein, (2) OH-mediated cerebral hypoperfusion impairs cognition and (3)
the two act synergistically to accelerate cognitive decline. Longitudinal
neuroimaging studies and clinical trials may help clarify the nature of this
relationship.
PMID- 27613155
TI - Contributions of the adaptive immune system to mood regulation: Mechanisms and
pathways of neuroimmune interactions.
AB - Clinical and basic studies of functional interactions between adaptive immunity,
affective states, and brain function are reviewed, and the neural, humoral, and
cellular routes of bidirectional communication between the brain and the adaptive
immune system are evaluated. In clinical studies of depressed populations,
lymphocytes-the principal cells of the adaptive immune system-exhibit altered T
cell subtype ratios and CD4+ helper T cell polarization profiles. In basic
studies using psychological stress to model depression, T cell profiles are
altered as well, consistent with stress effects conveyed by the hypothalamic
pituitary-adrenal axis and sympathetic nervous system. Lymphocytes in turn have
effects on behavior and CNS structure and function. CD4+ T cells in particular
appear to modify affective behavior and rates of hippocampal dentate gyrus
neurogenesis. These observations force the question of how such actions are
carried out. CNS effects may occur via cellular and molecular mechanisms whereby
effector memory T cells and the cytokine profiles they produce in the blood
interact with the blood-brain barrier in ways that remain to be clarified.
Understanding the mechanisms by which T cells polarize and interact with the
brain to alter mood states is key to advances in the field, and may permit
development of therapies that target cells in the periphery, thus bypassing
problems associated with bioavailability of drugs within the brain.
PMID- 27613161
TI - Trichomonas vaginalis: a possible foe to prostate cancer.
AB - Prostate cancer (PCA) is the most common malignancy in men in USA, and the role
of Trichomonas vaginalis (T. vag) in the development of PCA is still
controversial. Clonogenic assay, PCNA staining, TUNEL staining and caspase-3
activity assay were used to investigate the in vitro role of T. vag in human
prostate cancer. We further investigated the possible molecular mechanisms using
RT-PCR and immunohistochemical staining. Culture supernatant of T. vag inhibits
growth of PC-3 prostate cancer cells, and this correlated with upregulation of
p21. Culture supernatant of T. vag induced apoptosis of PC-3 cells, and this
correlated with downregulation of Bcl-2. The growth inhibition effect of culture
supernatant of T. vag is also demonstrated in another prostate cancer cell line
DU145, suggesting that its effect is not specific to one prostate cancer cell
line. Culture supernatant of T. vag inhibits growth of prostate cancer by
inhibition of proliferation and promotion of apoptosis. Such a study might be
helpful to address the association between PCA and infection of T. vag.
PMID- 27613162
TI - Pazopanib treatment slows progression and stabilizes disease in patients with
taxane-resistant cutaneous angiosarcoma.
AB - Although cutaneous angiosarcoma (cAS) has one of the worst prognoses among
malignant skin tumors, few effective drug options for secondary treatment have
been discovered to date because of the limited number of cases. Therefore, this
study was aimed at determining pazopanib's potential as a new cAS treatment
option. We retrospectively evaluated five patients with taxane-resistant
unresectable cAS treated with pazopanib at a university hospital. Their
characteristics and treatment outcomes were retrieved from their records.
Progression-free survival (PFS), overall survival (OS), disease progression, and
toxicity were evaluated; furthermore, the response to pazopanib was assessed in
relation to the expression of vascular endothelial growth factor receptor 2
(VEGFR-2). The median PFS from the time of pazopanib initiation was 94 days. Two
patients showed partial response, two showed stable disease, and one had
progressive disease in the case of the best overall response. VEGFR-2 expression
was positive in all cases, and patients with high expression had improved median
OS compared to that in those with low expression. VEGFR-2 expression was
correlated with a longer OS. The most common toxicities were hypertension and
anorexia followed by myelosuppression. This is the largest case series reported
wherein pazopanib was used for taxane-resistant cAS. Although the cytoreductive
effect and survival benefits were not significant in this small sample, we
consider pazopanib a valid treatment option for preserving patients' quality of
life. Our results suggest pazopanib treatment slows the progression of disease
and stabilizes it in patients with taxane-resistant cAS.
PMID- 27613163
TI - Resveratrol supplement inhibited the NF-kappaB inflammation pathway through
activating AMPKalpha-SIRT1 pathway in mice with fatty liver.
AB - Nonalcoholic fatty liver disease (NAFLD) is characterized by high levels of
nonesterified fatty acids (NEFA), inflammation, and hepatic steatosis.
Inflammation plays a crucial role in the development of fatty liver. Resveratrol
(RSV) supplement could improve inflammatory response and hepatic steatosis,
whereas the underlying mechanism was not well understood. In this study, mice fed
with high-fat diet (HFD) exhibited severe hepatic injury and high blood
concentrations of the inflammatory cytokines TNF-alpha, IL-6, and IL-1beta.
Hepatic NF-kappaB inflammatory pathway was over-induced in HFD mice. In vitro,
NEFA treatment further increased NF-kappaB pathway activation in mice
hepatocytes, which then promoted the synthesis of inflammatory cytokines.
Interestingly, RSV treatment significantly inhibited overactivation of NF-kappaB
pathway and improved hepatic steatosis. Furthermore, RSV further increased the
AMP-activated protein kinasealpha (AMPKalpha) phosphorylation and sirtuin1
(SIRT1) protein levels to inhibit overactivation of NF-kappaB pathway induced by
HFD or high levels of NEFA. AMPKalpha or SIRT1 inhibition significantly decreased
the improvement effect of RSV on the NF-kappaB pathway induced by high levels of
NEFA. Taken together, these findings indicate that RSV supplement decreases the
inflammatory level and improves hepatic steatosis through activating AMPKalpha
SIRT1 pathway. Therefore, these data suggested an important clinical application
of RSV in preventing NAFLD in humans.
PMID- 27613165
TI - Comparison of preoperative continuation and discontinuation of aspirin in
patients undergoing total hip or knee arthroplasty.
AB - INTRODUCTION: Preoperative discontinuation of aspirin (acetylsalicylic acid) can
reduce bleeding risk but may increase the risk of perioperative cardiovascular
events. MATERIALS AND METHODS: We retrospectively assessed the impact of
preoperative continuation versus discontinuation of aspirin compared with a
control group in a cohort of 739 consecutive patients undergoing total hip (THA)
(n = 396) or knee arthroplasty (TKA) (n = 343) at a tertiary hospital. Bleeding
risk, local complications, orthopaedic outcome, and cardiac and cerebral
complications were assessed. RESULTS: Four hundred and sixty-five patients did
not receive antithrombotic or full-dose anticoagulant medication, 175 patients
were taking low-dose aspirin, 99 vitamin K antagonists, clopidogrel, or a
combination of these drugs. Of the patients taking aspirin, 139 discontinued and
36 continued aspirin. Blood loss and local bleeding complications were comparable
in these two groups. TKA patients who continued aspirin more frequently showed
marked knee swelling after 1 week than those discontinuing aspirin (35.1 vs. 81.3
%; p = 0.001). However, orthopaedic outcome did not differ significantly between
the two groups. There was a trend towards an increased risk of cardiac
complications in patients who discontinued aspirin (6.5 vs. 0.0 %; p = 0.107).
CONCLUSIONS: Continuation or discontinuation of aspirin did not show a
statistically significant difference in the risk of relevant perioperative
bleeding complications in our study. Continuation of aspirin was associated with
a transitory increase in knee swelling, but had no effect on orthopaedic outcome.
Continuation of aspirin may be associated with a favourable perioperative cardiac
outcome. Our data support perioperative continuation of aspirin intake in
patients undergoing THA or TKA.
PMID- 27613164
TI - A novel role of G protein-coupled receptor kinase 5 in urotensin II-stimulated
cellular hypertrophy in H9c2UT cells.
AB - Urotensin II (UII) is a neural hormone that induces cardiac hypertrophy and may
be involved in the pathogenesis of cardiac remodeling and heart failure.
Hypertrophy has been linked to histone deacetylase 5 (HDAC5) phosphorylation and
nuclear factor kappaB (NF-kappaB) translocation, both of which are predominantly
mediated by G protein-coupled receptor kinase 5 (GRK5). In the present study, we
found that UII rapidly and strongly stimulated nuclear export of HDAC5 and
nuclear import of NF-kappaB in H9c2 cells overexpressing the urotensin II
receptor (H9c2UT). Hence, we hypothesized that GRK5 and its signaling pathway may
play a role in UII-mediated cellular hypertrophy. H9c2UT cells were transduced
with a GRK5 small hairpin RNA interference recombinant lentivirus, resulting in
the down-regulation of GRK5. Under UII stimulation, reduced levels of GRK5 in
H9c2UT cells led to suppression of UII-mediated HDAC5 phosphorylation and
activation of the NF-kappaB signaling pathway. In contrast, UII-mediated
activations of ERK1/2 and GSK3alpha/beta were not affected by down-regulation of
GRK5. In a cellular hypertrophy assay, down-regulation of GRK5 significantly
suppressed UII-mediated hypertrophy of H9c2UT cells. Furthermore, UII-mediated
cellular hypertrophy was inhibited by amlexanox, a selective GRK5 inhibitor, in
H9c2UT cells and neonatal cardiomyocytes. Our results suggest that GRK5 may be
involved in a UII-mediated hypertrophic response via activation of NF-kappaB and
HDAC5 at least in part by ERK1/2 and GSK3alpha/beta-independent pathways.
PMID- 27613166
TI - Incorporating Geriatric Medicine Providers into the Care of the Older Adult with
Cancer.
AB - A significant proportion of cancer patients and survivors are age 65 and over.
Older adults with cancer often have more complex medical and social needs than
their younger counterparts. Geriatric medicine providers (GMPs) such as
geriatricians, geriatric-trained advanced practice providers, and geriatric
certified registered nurses have expertise in caring for older adults, managing
complex medical situations, and optimizing function and independence for this
population. GMPs are not routinely incorporated into cancer care for older
adults; however, their particular skill set may add benefit at many points along
the cancer care continuum. In this article, we review the role of geriatric
assessment in the care of older cancer patients, highlight specific case
scenarios in which GMPs may offer additional understanding and insight in the
care of older adults with cancer, and discuss specific mechanisms for
incorporating GMPs into oncology care.
PMID- 27613168
TI - Optimal Use of BRAF Targeting Therapy in the Immunotherapy Era.
AB - PURPOSE OF REVIEW: The therapeutic landscape for metastatic melanoma has been
revolutionized in recent years. This review will discuss existing evidence for
therapeutic approaches for BRAF-mutated metastatic melanoma. RECENT FINDINGS:
Clinical trials involving combined BRAF/MEK inhibition with either vemurafenib
plus cobimetinib or dabrafenib plus trametinib have shown improved overall
survival compared to monotherapy with BRAF inhibitors alone. In a subset of
patients with good prognostic factors, long-term clinical benefit has been noted.
Simultaneously, developments in immunotherapy have suggested long-lasting
survival for some patients. In advanced BRAF-mutated melanoma, both BRAF/MEK
inhibition and immunotherapy agents show improved overall survival and, in a
small population of patients, prolonged and long-term benefit as compared to
standard chemotherapy. Trials are currently underway evaluating sequencing of
these therapies and the safety of targeted therapy plus immunotherapy
combinations.
PMID- 27613167
TI - The Wide Experience of the Sequential Therapy for Patients with Metastatic Renal
Cell Carcinoma.
AB - Sequential targeted therapies are the standard of care for patients with
metastatic renal cell carcinoma (mRCC). Several drugs are available for patients
whose disease progresses while they receive initial tyrosine kinase inhibitor
(TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor),
everolimus (an inhibitor of the mechanistic target of rapamycin) or additional
TKIs. Until now, there has been no clinical evidence to support the use of one
strategy versus another, so investigators and physicians rely on experience,
judgement and findings from molecular analyses to select the appropriate
treatment. However, with the arrival of nivolumab and cabozantinib that provide
an overall survival higher than other alternative treatments, therapeutic
strategies may have changed. Here, we discuss findings from preclinical and
clinical studies that might help clinicians to choose the optimal treatment
approach for patients with mRCC who progress to initial therapy.
PMID- 27613169
TI - Incidence and risk of heart failure in systemic lupus erythematosus.
AB - BACKGROUND: Although case series suggest a higher burden of cardiovascular risk
factors in patients with systemic lupus erythematosus (SLE) compared with the
general population, the association between SLE and heart failure (HF) remains
undefined. We sought to investigate the incidence and risk of HF in patients with
SLE. METHODS: In April 2016, we performed a retrospective cohort analysis using
the Explorys platform, which provides aggregated electronic medical record data
from 26 major integrated healthcare systems across the USA from 1999 to present.
Demographic and regression analyses were performed to assess the impact of SLE on
HF incidence. RESULTS: Among 45 284 540 individuals in the database, we
identified 95 400 (0.21%) with SLE and 98 900 (0.22%) with a new diagnosis of HF
between May 2015 and April 2016. HF incidence was markedly higher in the SLE
group compared with controls (0.97% vs 0.22%, relative risk (RR): 4.6 (95% CI 4.3
to 4.9)), as were other cardiovascular risk factors. In regression analysis, SLE
was an independent predictor of HF (adjusted OR: 3.17 (2.63 to 3.83), p<0.0001).
RR of HF was highest in young males with SLE (65.2 (35.3 to 120.5) for age 20
24), with an overall trend of increasing absolute risk but decreasing RR with
advancing age in both sexes. Renal involvement in SLE correlated with earlier and
higher incidence of HF. CONCLUSIONS: The findings of this study suggest that
patients with SLE have significantly higher risk of developing HF and a worse
cardiovascular risk profile compared with the general population. These results
need to be confirmed by prospective studies.
PMID- 27613170
TI - Safety and efficacy of paramedic treatment of regular supraventricular
tachycardia: a randomised controlled trial.
AB - INTRODUCTION: Supraventricular tachycardias (SVTs) are a common cause of acute
hospital presentations. Adenosine is an effective treatment. To date, no studies
have directly compared paramedic-with hospital-delivered treatment of acute SVT
with adenosine. METHOD: Randomised controlled trial comparing the treatment of
SVT and discharge by paramedics with conventional emergency department (ED)-based
care. Patients were excluded if they had structural heart disease or
contraindication to adenosine. Discharge time, follow-up management, costs and
patient satisfaction were compared. RESULTS: Eighty-six patients were enrolled:
44 were randomised to paramedic-delivered adenosine (PARA) and 42 to conventional
care (ED). Of the 37 patients in the PARA group given adenosine, the tachycardia
was successfully terminated in 81%. There was a 98% correlation between the
paramedics' ECG diagnosis and that of two electrophysiologists. No patients had
any documented adverse events in either group. The discharge time was lower in
the PARA group than in the ED group (125 min (range 55-9513) vs 222 min (range 72
26 153); p=0.01), and this treatment strategy was more cost-effective (L282 vs
L423; p=0.01). The majority of patients preferred this management approach. Being
treated and discharged by paramedics did not result in the patients being less
likely to receive ongoing management of their arrhythmia and cardiology follow
up. CONCLUSIONS: Patients with SVT can effectively and safely be treated with
adenosine delivered by trained paramedics. Implementation of paramedic-delivered
acute SVT care has the potential to reduce healthcare costs without compromising
patient care. TRIAL REGISTRATION NUMBER: NCT02216240.
PMID- 27613176
TI - Clinical recovery and health-related quality of life in ischaemic stroke
survivors receiving thrombolytic treatment: a 1-year follow-up study.
AB - The aims of this study were to examine prospectively the course of neurological
and functional recovery and health related quality of life (HRQoL) in ischaemic
stroke patients after intravenous thrombolysis, to assess the 1-year outcome and
to determine the early predictors. A group of 53 consecutive patients were
assessed at admission to the acute stroke unit (T0), before their discharge (T1),
and at 3 (T2) and 12 (T3) months after hospital discharge. The National
Institutes of Health Stroke Scale (NIHSS), the Barthel Index (BI) and the Stroke
Specific Quality of Life Scale (SSQoL) were used to evaluate stroke severity,
functional disability and health related quality of life (HRQoL). A good outcome
was defined as simultaneous improvement in all three scales. At T0, 83 % of the
patients had severe or moderate neurological impairment. Additionally, 77 %
demonstrated very severe or severe disability when assessed by the BI. 74 and 79
% of the patients reported an acceptable HRQoL at 3 and 12 months following
discharge, respectively. Neurological and functional status improved
significantly over time with most changes occurring during hospitalization and
the subsequent 3 months. At T3, 75.5 % of the patients had the good outcome which
had been independently predicted by the level of stroke related disability at T0.
A majority of the stroke survivors treated with thrombolysis achieved a good
outcome. The measurement of stroke specific HRQoL, as a tool for gathering
information from the patient, should be incorporated in the assessment of post
stroke recovery and outcome.
PMID- 27613178
TI - [Evidence-based neurorehabilitation].
PMID- 27613177
TI - Evaluation of von Willebrand factor and ADAMTS-13 antigen and activity levels in
sickle cell disease patients in Kuwait.
AB - Sickle cell disease (SCD) is a severe form of hemolytic anemia characterized by
chronic hemolysis and is associated with increased thrombotic risk. Elevated von
Willebrand factor (vWF) levels in SCD have been attributed to increased secretion
and impaired processing by its cleaving protease ADAMTS-13. In this study we
measured vWF and ADAMTS-13 antigen and activity levels in our SCD patients.
Hematological and biochemical parameters for 59 SCD patients (20 children and 39
adults) were analyzed and compared to 59 age- and sex-matched controls.
Commercially available ELISA kits were used to measure vWF and ADAMTS-13 antigen
and activity levels in patients and controls. Patients had significantly higher
levels of vWF (p < 0.006) and ADAMTS-13 activity (p < 0.006) compared to
controls. When patients were analyzed according to age and genotype, adult
patients (23 SS and 16 Sbeta0thal) maintained higher vWF antigen levels (p <
0.001), but with reduced ADAMTS-13 activity to vWF:Ag ratio (p < 0.003) compared
to controls. Pediatric patients (8 SS and 12 Sbeta0thal) had comparable vWF
antigen levels to controls (p > 0.05), but had higher levels of ADAMTS-13
activity (p < 0.011) and ADAMTS-13 activity to vWF:Ag ratio (p < 0.038). Age is
an important factor to consider when vWF and ADAMTS-13 proteins are analyzed
among our patients. Increased vWF in adult patients may be attributed to
increased production and resistance of vWF to proteolysis rather than ADAMTS-13
deficiency. This outcome was not seen in pediatric patients as higher ADAMTS-13
activity maintained vWF antigen at comparable levels to normal controls.
PMID- 27613179
TI - [No high-level evidence for the suicide prevention through antidepressants or
clozapine].
PMID- 27613171
TI - Associations with intraocular pressure across Europe: The European Eye
Epidemiology (E3) Consortium.
AB - Raised intraocular pressure (IOP) is the most important risk factor for
developing glaucoma, the second commonest cause of blindness globally.
Understanding associations with IOP and variations in IOP between countries may
teach us about mechanisms underlying glaucoma. We examined cross-sectional
associations with IOP in 43,500 European adults from 12 cohort studies belonging
to the European Eye Epidemiology (E3) consortium. Each study conducted
multivariable linear regression with IOP as the outcome variable and results were
pooled using random effects meta-analysis. The association of standardized study
IOP with latitude was tested using meta-regression. Higher IOP was observed in
men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index
(0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17
mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure
(0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction
(0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped
trend was observed between age and IOP, with IOP increasing up to the age of 60
and decreasing in participants older than 70 years. We found no significant
association between standardized IOP and study location latitude (P = 0.76).
Novel findings of our study include the association of lower IOP in taller people
and an inverted-U shaped association of IOP with age. We found no evidence of
significant variation in IOP across Europe. Despite the limited range of latitude
amongst included studies, this finding is in favour of collaborative pooling of
data from studies examining environmental and genetic determinants of IOP in
Europeans.
PMID- 27613181
TI - Health secretary promises "world class" hospital IT.
PMID- 27613180
TI - Police-Recorded Crime and Perceived Stress among Patients with Type 2 Diabetes:
the Diabetes Study of Northern California (DISTANCE).
AB - While stress has been linked to poor health outcomes, little is known about the
impact of objective measures of neighborhood crime on stress in patients with
chronic disease. Using the Kaiser Permanente Diabetes Study of Northern
California (DISTANCE), we examined associations between police-recorded crime
(2005-2007) and stress (Perceived Stress Scale-4) in four large Northern
California cities (Oakland, Sacramento, San Francisco, and San Jose). We
performed stratified analysis by gender and race/ethnicity using generalized
linear regression models. In our study sample (n = 3188, mean age 59, range 30
77), 10 % reported high stress. In adjusted analyses, higher neighborhood all
crimes rate was associated with modest increase in high stress for African
American (OR = 1.10; 95 % CI 1.02-1.22) and Latina women (OR = 1.36; 95 % CI 1.10
1.67) and property crime showed similar associations with stress for these groups
of women. Visible crime was associated with stress only for Latina women (OR =
1.43; 95 % CI 1.14-1.78). We found no association between crime and stress among
men or other racial/ethnic groups of women. High crime levels may
disproportionately impact health among certain subpopulations. Studies using
additional measures of stress are necessary to differentiate the health impact of
crime-related stress from other forms of stressors among individuals living with
diabetes.
PMID- 27613182
TI - Determining the Contribution of Nearby Power Plants to Deposited Foliar Dust: A
Case Study of BTPS, Bokaro.
AB - Deposition of dust particles on foliage surfaces helps to filter airborne dust
particles that occur predominantly in areas near thermal power plants (TPPs).
Highly dust-laden foliage surrounding TPPs is a serious issue affecting the
vegetation and facade greening adversely. Fly ash (FA) generated by TPPs have an
adverse impact on the growth and development of flora. Therefore, identification
of their percentage contribution on foliar dust (FD) is of utmost importance. The
present study attempted to identify all the contributing sources to FD.
Morphological and chemical characterization of FD, FA, and road dust (RD) has
been evaluated, followed by their multivariate statistical analysis.
Contamination of FD from different sources was estimated by using field emission
scanning electron microscope (FE-SEM) coupled with energy dispersive X-ray
technique (EDX), Fourier transform infrared spectroscope (FTIR), and atomic
absorption spectrophotometer techniques. Particle size distribution of FD
revealed that the major portion of FD was <2 um. FE-SEM and EDX analysis
confirmed contamination of FD by FA, resuspension of RD, and local sources. FTIR
peaks depicted the presence of different functional groups, including silica from
nearby roads, saturated-nonsaturated, and aromatic organic functional groups
originating predominantly from different activities of TPPs and traffic. Results
of IR were in agreement with results obtained in physicochemical analyses. Heavy
metals analysis of FA demonstrated high concentration of carcinogens Cr, Cu, Cd,
and Ni and could be considered a marker to them. Certain heavy metals (Fe, Co,
Mn, Pb, and Zn) were found to be in the order RD > FA > FD. This explores the
necessity for considering other sources other than TPP sources. Principal
component analysis (PCA) of heavy metals present in FD revealed that the sampling
area was chiefly influenced from three sources: Bokaro thermal power station (55
%), RD (18 %), and local sources (27 %). Cluster analysis complemented the
results of Pearson correlation matrix and PCA. Analyses illustrated the
substantial influence of TPPs along with other source's significance in
contamination of FD.
PMID- 27613183
TI - Hybrid ablation for atrial fibrillation: a systematic review.
AB - PURPOSE: Hybrid ablation for AF is performed in a growing number of centers. Due
to absence of guidelines, operative approaches and perioperative care differ per
center. In this review, an overview of findings from published studies on hybrid
ablations is given, and related topics are discussed (e.g., one- and two-stage
approaches, lesion sets, and patient management). METHODS: A systematic
literature search was performed in the PubMed and Embase databases. All
identified articles were screened and checked for eligibility by the two authors.
RESULTS: Twelve studies describing a total of 563 patients were selected. Due to
substantial differences in approaches (one-stage, two-stage, sequential),
surgical techniques (bilateral or monolateral thoracoscopy, subxiphoideal,
transabdominal), energy sources (unipolar, bipolar), lesion sets (applying left
or right atrial lesions), periprocedural care and endpoints (monitoring,
definition of recurrence), and success rates (sinus rhythm after a mean of 26
months) are difficult to compare and varied from 27 % (without antiarrhythmic
drugs, AADs) to 94 % (with AADs). For studies using bipolar devices, success
rates with the use of antiarrhythmic drugs were at least 71 %. Major
complications such as bleeding, sternotomy, and death occurred in 7 % of the
total population (of which ten complications, 16 %, occurred in the concomitant
cardiac surgery hybrid group). CONCLUSION: The field of AF ablation has
dramatically changed over the past years, with one of the most recent
developments the hybrid AF ablation. Lack of matching data hinders drawing
conclusions and creating guidelines. Early results however are encouraging. More
data are awaiting and needed.
PMID- 27613184
TI - What is the cost of non-response to cardiac resynchronization therapy?
Hospitalizations and healthcare utilization in the CRT-D population.
AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment for
heart failure (HF) with left ventricular systolic dysfunction and prolonged QRS
interval. However, one third of patients do not benefit from treatment. This
study compares the heart failure hospitalization (HFH) rates and corresponding
costs between responders and non-responders to CRT. METHODS: At a single center
in New Jersey, we enrolled patients with de novo CRT-D implants between January
2011 and July 2013. Medical history at implant and all subsequent
hospitalizations were collected. A retrospective chart review of the cardiology
visit at or closest to 12 months post-CRT implant was performed, and patients
were classified into responders and non-responders. Universal billing records (UB
04), ICD-9-CM diagnoses, and procedure codes were used to determine whether each
hospitalization was due to HF. For each heart failure hospitalization (HFH), an
MS-DRG-based US national average Medicare reimbursement was determined. HFH rates
and associated payor costs were compared between responders and non-responders
using negative binomial regression and non-parametric bootstrapping (*10,000),
respectively. RESULTS: CRT response was determined in 135 patients (n = 103
responders, n = 32 non-responders, average follow-up 1.4 years). Demographics,
pre-implant HF characteristics, NYHA Class, QRS duration, ejection fraction (EF),
left bundle branch block (LBBB) status, and co-morbidities were not statistically
different between the two groups. The HFH rate was significantly lower in
responders (0.43/patient year) compared to non-responders (0.96/patient year, IRR
= 0.45, 95 % CI (0.23 0.90), P = 0.0197). Average US national Medicare
reimbursement for the responder group (US$7205/patient year) was 48 % lower than
that for the non-responder group (US$13,861/patient year, P = 0.035). CONCLUSION:
In this single-center retrospective study, responders to CRT had significantly
lower rates of post-implant heart failure hospitalization rate and reduced
associated payor costs compared to non-responders. Therapies that increase CRT
response rates can substantially reduce healthcare utilization.
PMID- 27613185
TI - Right atrial lead fixation type and lead position are associated with significant
variation in complications.
AB - PURPOSE: Optimal atrial pacemaker lead position and fixation mechanism have not
been determined with regard to effect on complications. We aimed to determine the
association between atrial lead-related complications and varying atrial lead tip
positions and lead fixation mechanisms. METHODS: All patients who underwent dual
chamber pacemaker implant between 2004 and 2014 were retrospectively reviewed for
atrial lead tip position and fixation type. Lead-related complications were
assessed by electronic medical record review. Complication rates were compared at
1 year by chi-square analysis and at 5 years using a Kaplan-Meier analysis.
RESULTS: During the study period, 3451 patients (mean age 73.9, 53.4 % male)
underwent dual-chamber pacemaker placement. Active fixation leads were associated
with a higher incidence of pericardial effusion (81 (2.9 %) vs. 6 (1.0 %), p =
0.005) and pericardiocentesis (46 (1.6 %) vs. 2 (0.3 %), p = 0.01) at 1 year
compared to passive fixation leads. There was no difference in overall
complication rates by fixation type (161 (5.7 %) vs. 29 (4.6 %), p = 0.26). Low
atrial septal lead tip position was associated with a higher rate of lead
dislodgement (10 (15.2 %)) compared to appendage (46 (1.6 %)), free wall (10 (2.1
%)), or high atrial septal (2 (4.7 %)) positions (p < 0.001). This difference was
also reflected in a significantly increased need for lead revision and overall
complications. A multivariate analysis which included potential confounders
confirmed the association of active fixation leads with an increased rate of
perforation-related complications (p = 0.03) and septal lead location with
increased rates of dislodgement (p < 0.001). CONCLUSIONS: Active compared to
passive lead fixation increases the risk for pericardial effusion requiring
pericardiocentesis. There is a clear association between low atrial septal lead
position and lead dislodgement requiring lead revision.
PMID- 27613186
TI - Detection of human papillomavirus-16 DNA in archived clinical samples of breast
and lung cancer patients from North Pakistan.
AB - PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded
as a key player in the development of various genital cancers, most notably
cervical cancer. It has also been associated with some non-genital cancers. A
subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological
involvement has been suggested for breast and lung cancer as well. However,
reports regarding the HPV DNA detection vary widely from different parts of the
world. Due to scarcity of local data in this regard, the current study aimed at
retrospective detection of HPV presence in the archival samples of breast and
lung cancer patients from north part of the country. METHODS: A total of 55
formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of
breast (n = 46) and lung (n = 9) were collected for this study. Genotyping for
HPV16 and 18 was carried out through PCR. RESULTS: HPV16 DNA was found in both
breast and lung carcinoma samples with the prevalence rate of 17 and 11 %,
respectively. An interesting association was found between ER/PR
(Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor
receptor-2) positivity with HPV occurrence in breast tumours. CONCLUSION: Current
study shows the presence of HPV16 DNA in archived clinical biopsy sections from
breast and lung cancers (17, 11 %), respectively. A positive correlation of HPV16
presence was found with ER/PR and HER2-positive breast cancers. These initial
findings warrant further investigation in order to determine HPV prevalence and
aetiological role in local cancers, especially in ER/PR/HER2-positive breast
cancers on a larger scale.
PMID- 27613187
TI - Vitamin C in synergism with cisplatin induces cell death in cervical cancer cells
through altered redox cycling and p53 upregulation.
AB - PURPOSE: Cervical cancer is the second most prevalent cancer in women worldwide.
Survival of patients has been improved by cisplatin-based chemotherapy, but its
effectiveness is limited due to its adverse effects on many tissues, especially
nephrotoxicity. To optimize the efficacy of CDDP, we propose a combination
therapy using natural products with minimal side effects. Vitamin C being a
natural antioxidant is capable of selectively targeting cancer cells at
pharmacological concentrations. Vitamin C synergistically enhances the activity
of chemotherapeutic agents without increasing toxicity to normal cells.
Therefore, we exploited co-therapy with cisplatin and vitamin C to kill cervical
cancer cells. METHODS: We elucidated the role of CDDP and VC on cervical cancer
cell line (SiHa) by using cell growth assays, DNA fragmentation analysis, comet
assay, in vitro morphological assessment of apoptosis (AO/EB and DAPI staining),
ROS analysis by DCFDA, flow cytometry, biochemical assays (GST, GSH, NO,
catalase, TPA) and Western blotting. RESULTS: Our results clearly demonstrated
that CDDP and VC treatment exhibited ameliorative effect on induction of cell
death by p53 overexpression and generation of hydrogen peroxide in SiHa cells,
thereby reducing the dosage of CDDP required to induce cell death in cancer
cells. CONCLUSIONS: These studies provide novel approaches to combat cisplatin
resistance in cervical cancer.
PMID- 27613188
TI - Severe weight loss during preoperative chemoradiotherapy compromises survival
outcome for patients with locally advanced rectal cancer.
AB - PURPOSE: In addition to tumor factors, poor nutritional status before and during
anti-tumor treatment might compromise prognosis in several types of cancer. This
study was done to determine the impact of weight loss during preoperative
chemoradiotherapy (CRT) on the survival outcome of patients with locally advanced
rectal cancer (LARC). METHODS: The retrospective study examined consecutive
patients with LARC who underwent preoperative CRT followed by radical resection
in a single institute, between 2003 and 2013. Correlation of proportional body
mass index (BMI) change after preoperative CRT and patient's demographics, tumor
characteristics, treatment parameters, CRT-related toxicity, disease-free
survival (DFS) and overall survival (OS) were investigated. RESULTS: A total of
364 patients were enrolled, and BMI loss was found in 243 patients (66.2 %) after
preoperative CRT. Severe weight loss (SWL) was defined as BMI loss >=7 %. Thirty
nine (10.7 %) cases were enrolled in SWL cohort and found to have higher
incidence of diarrhea (P = 0.033), renal disorder (P = 0.033) and grade 3-4
radiation proctitis (P = 0.041). Although no significant difference was found in
3-year DFS, patients in SWL cohort showed significantly worse 3-year OS rate
(71.8 vs 88.0 %, P = 0.030) than the others. In univariate analysis, BMI loss >=7
%, completed dose of preoperative chemotherapy, pathologic T and N stages were
correlated with OS (all P < 0.05). In multivariable analysis, BMI loss >=7 % (HR
1.984; 95 % CI 1.061-3.709; P = 0.032) remained the independent prognostic factor
for OS. CONCLUSIONS: Our results demonstrate that SWL during preoperative CRT
indeed compromises survival outcome in patients with LARC. Routine nutritional
monitoring and nutritional support during preoperative CRT are suggested as the
integral part of the multidisciplinary approach for these patients.
PMID- 27613189
TI - PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr
virus-associated hemophagocytic lymphohistiocytosis.
AB - BACKGROUND: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV
HLH) is the most frequent subtype of secondary HLH triggered by infections.
Previous studies have shown that ~30 % or more of patients with EBV-HLH do not
respond to standard therapy. This study investigated the efficacy and safety
profile of a modified DEP regimen in combination with PEG-aspargase (L-DEP) as a
salvage therapy for refractory EBV-HLH. METHODS: In this study from October 2014
to October 2015, 28 patients with refractory EBV-HLH received a L-DEP regimen at
the Beijing Friendship Hospital, Capital Medical University. Treatment efficacy
and adverse events were evaluated at 2 and 4 weeks after L-DEP treatment.
RESULTS: Median EBV-DNA concentrations before and 2 weeks after receiving the L
DEP regimen were 9.6 * 10(5) (1.5 * 10(4) - 1 * 10(9)) copies/mL and 2.2 * 10(5)
(3.8 * 10(2) - 1.2 * 10(7)) copies/mL, respectively; the post-treatment values
were significantly lower than that of the pretreatment (P = 0.048). Nine of the
28 study patients achieved complete response (CR) and 15 partial response (PR),
resulting in an overall response rate of 85.7 % (CR+PR). Four patients who did
not achieve response died within 4 weeks of receiving L-DEP. Thirteen of the 24
patients who achieved partial or complete response received subsequent allogenic
hematopoietic stem cell transplantation (allo-HSCT). Ten of these 13 patients
survived until 1 March 2016. The major adverse effects of the L-DEP regimen were
high serum amylase concentrations, abnormal liver function, and coagulation
disorders. CONCLUSIONS: This study suggests that L-DEP is a safe and effective
salvage therapy prior to allo-HSCT for refractory EBV-HLH and increases the
possibility of such patients receiving allo-HSCT. A prospective multicenter large
scale clinical trial that aims to validate the L-DEP regimen for refractory EBV
HLH is currently underway (ClinicalTrails.gov Identifier: NCT02631109).
PMID- 27613191
TI - Poor Health Behaviors Prior to Laparoscopic Sleeve Gastrectomy Surgery.
AB - INTRODUCTION: Identifying eating and lifestyle behaviors prior to bariatric
surgery may assist in better selecting and preparing patients and might lead to
improved success rate. The current study aimed to assess eating behaviors and
lifestyle trends among laparoscopic sleeve gastrectomy (LSG) candidates and to
compare those trends between genders. METHODS: This descriptive study was
conducted in the bariatric clinic at the Haifa Assuta Medical Center. Data was
gathered from medical records of LSG candidates that were evaluated before
surgery in our institution between 2008 and 2011. The data included demographics,
comorbidities, anthropometrics, weight management history, and lifestyle
parameters. Eating pattern and eating habits were determined by eating habits
questionnaires. RESULTS: A total of 266 LSG surgery candidates (71.4 % female)
with an average age of 40.7 +/- 10.9 years and pre-surgery BMI of 42.4 +/- 4.8
kg/m2 were studied. More than half of the patients have family history of obesity
and their onset of obesity was before the age of 18 years (54.5 and 57.9 %,
respectively). Most of the patients reported on poor eating habits and sedentary
lifestyle: 65.1 % do not eat regular meals, 70.3 % skip over breakfast, 61.9 %
presented loss of control eating, 45 % frequently consume sweets, and 80.1 % were
classified as none active. There were no differences in eating patterns or
lifestyle parameters between genders. CONCLUSION: High occurrence of unhealthy
eating habits and a non-active lifestyle were detected in morbid obese candidates
for LSG surgery. More efforts should be directed towards nutritional and
lifestyle education prior to the surgery.
PMID- 27613190
TI - Human corneal cell culture models for drug toxicity studies.
AB - In vivo toxicity and absorption studies of topical ocular drugs are problematic,
because these studies involve invasive tissue sampling and toxic effects in
animal models. Therefore, different human corneal models ranging from simple
monolayer cultures to three-dimensional models have been developed for
toxicological prediction with in vitro models. Each system has its own set of
advantages and disadvantages. Use of non-corneal cells, inadequate
characterization of gene-expression profiles, and accumulation of genomic
aberrations in human corneal models are typical drawbacks that decrease their
reliability and predictive power. In the future, further improvements are needed
for verifying comparable expression profiles and cellular properties of human
corneal models with their in vivo counterparts. A rapidly expanding stem cell
technology combined with tissue engineering may give future opportunities to
develop new tools in drug toxicity studies. One approach may be the production of
artificial miniature corneas. In addition, there is also a need to use large
scale profiling approaches such as genomics, transcriptomics, proteomics, and
metabolomics for understanding of the ocular toxicity.
PMID- 27613194
TI - Deep Fish.
AB - Zebrafish ( Danio rerio) is an important vertebrate model organism in biomedical
research, especially suitable for morphological screening due to its transparent
body during early development. Deep learning has emerged as a dominant paradigm
for data analysis and found a number of applications in computer vision and image
analysis. Here we demonstrate the potential of a deep learning approach for
accurate high-throughput classification of whole-body zebrafish deformations in
multifish microwell plates. Deep learning uses the raw image data as an input,
without the need of expert knowledge for feature design or optimization of the
segmentation parameters. We trained the deep learning classifier on as few as 84
images (before data augmentation) and achieved a classification accuracy of 92.8%
on an unseen test data set that is comparable to the previous state of the art
(95%) based on user-specified segmentation and deformation metrics. Ablation
studies by digitally removing whole fish or parts of the fish from the images
revealed that the classifier learned discriminative features from the image
foreground, and we observed that the deformations of the head region, rather than
the visually apparent bent tail, were more important for good classification
performance.
PMID- 27613192
TI - Limitations of the DiaRem Score in Predicting Remission of Diabetes Following
Roux-En-Y Gastric Bypass (RYGB) in an ethnically Diverse Population from a Single
Institution in the UK.
AB - PURPOSE: This study aimed to determine the predictive power of the DiaRem score
following Roux-en-Y gastric bypass to identify patients who would have diabetes
remission at 1 year in an ethnically diverse population. METHODS: We performed a
retrospective review of 262 patients with type 2 diabetes mellitus who underwent
RYGB at the Imperial Weight Centre, UK, from 2007 to 2014. Data was collected on
the parameters required to calculate the DiaRem score as well as pre- and post
surgical weight and the ethnicity of the subjects. RESULTS: The studied cohort
was ethnically diverse (61.3 % Caucasian, 10.3 % Asian, 5.3 % black, 2.6 % mixed
and 20.6 % other). At 1-year post-surgery, there were significant reductions in
mean weight (133.4 to 94.3 kg) and BMI (46.7 to 33.3 kg/m2). The mean HbA1c
decreased from 8.2 to 6.1 %, and 32.5 % of the cohort underwent either partial or
complete remission. 67.8 % of the patients that were classified in group 1 of the
DiaRem score (most likely to have remission) had complete remission. However,
22.9 % of the patients predicted to have the least chance of remission had either
partial or complete remission. CONCLUSIONS: In this ethnically diverse cohort,
the DiaRem score remains a useful tool to predict diabetes remission in those
that have a low DiaRem score (high chance for remission) but was more limited in
its predictive power in those with a high DiaRem score (least likely to have
remission). Caution must be used in the application of this model in populations
other than the US white Caucasian population used to derive the score.
PMID- 27613193
TI - Collagen based barrier membranes for periodontal guided bone regeneration
applications.
AB - Certain cell populations within periodontal tissues possess the ability to induce
regeneration, provided they have the opportunity to populate the wound or defect.
Guided regeneration techniques have been investigated for regenerating
periodontal tissues and such therapies usually utilize barrier membranes. Various
natural and synthetic barrier membranes have been fabricated and tested to
prevent epithelial and connective tissue cells from invading while allowing
periodontal cells to selectively migrate into the defect. This paper focuses on
the literature relevant to the use and potential of resorbable collagen membranes
in GBR procedures, sites of periodontal and intrabony defects, in cases of socket
and alveolar ridge preservation and at implant sites. The results of their use in
GBR procedures has shown them to be effective and comparable with non-resorbable
membranes with regards to clinical attachment gain, probing depth reduction and
defect bone filling. They have also shown to prevent epithelial ingrowth into the
defect space during the initial wound healing phase postsurgically. Collagen
membranes have also been used for root coverage and GBR procedures and have shown
good success rates comparable to subepithelial connective tissue grafts and
expanded-polytetrafluoroethylene (e-PTFE) membranes. The future for periodontal
tissue engineering is very exciting with the use of barrier membranes expected to
continue playing a critical role. However, long-term clinical trials are required
to further evaluate and confirm the efficacy of the available collagen barrier
membranes for periodontal and bone regeneration use.
PMID- 27613195
TI - The DAG1 transcription factor negatively regulates the seed-to-seedling
transition in Arabidopsis acting on ABA and GA levels.
AB - BACKGROUND: In seeds, the transition from dormancy to germination is regulated by
abscisic acid (ABA) and gibberellins (GAs), and involves chromatin remodelling.
Particularly, the repressive mark H3K27 trimethylation (H3K27me3) has been shown
to target many master regulators of this transition. DAG1 (DOF AFFECTING
GERMINATION1), is a negative regulator of seed germination in Arabidopsis, and
directly represses the GA biosynthetic gene GA3ox1 (gibberellin 3-beta
dioxygenase 1). We set to investigate the role of DAG1 in seed dormancy and
maturation with respect to epigenetic and hormonal control. RESULTS: We show that
DAG1 expression is controlled at the epigenetic level through the H3K27me3 mark
during the seed-to-seedling transition, and that DAG1 directly represses also the
ABA catabolic gene CYP707A2; consistently, the ABA level is lower while the GA
level is higher in dag1 mutant seeds. Furthermore, both DAG1 expression and
protein stability are controlled by GAs. CONCLUSIONS: Our results point to DAG1
as a key player in the control of the developmental switch between seed dormancy
and germination.
PMID- 27613197
TI - Establishment and characterization of new wheat-Thinopyrum ponticum addition and
translocation lines with resistance to Ug99 races.
PMID- 27613196
TI - Hereditary risk factors for thrombophilia and probability of venous
thromboembolism during pregnancy and the puerperium.
AB - Venous thromboembolism (VTE) is a leading cause of maternal mortality. Few
studies have evaluated the individual risk of gestational VTE associated with
heritable thrombophilia, and current recommendations for antenatal
thromboprophylaxis in women with severe thrombophilia such as homozygous factor V
Leiden mutation (FVL) depend on a positive family history of VTE. To better
stratify thromboprophylaxis in pregnancy, we aimed to estimate the individual
probability (absolute risk) of gestational VTE associated with thrombophilia and
to see whether these risk factors are independent of a family history of VTE in
first-degree relatives. We studied 243 women with the first VTE during pregnancy
and the puerperium and 243 age-matched normal women. Baseline incidence of VTE of
1:483 pregnancies in women >=35 years and 1:741 deliveries in women <35 years was
assumed, according to a recent population-based study. In women >=35 years (<35
years), the individual probability of gestational VTE was as follows: 0.7% (0.5%)
for heterozygous FVL; 3.4% (2.2%) for homozygous FVL; 0.6% (0.4%) for
heterozygous prothrombin G20210A; 8.2% (5.5%) for compound heterozygotes for FVL
and prothrombin G20210A; 9.0% (6.1%) for antithrombin deficiency; 1.1% (0.7%) for
protein C deficiency; and 1.0% (0.7%) for protein S deficiency. These results
were independent of a positive family history of VTE. We provide evidence that
unselected women with these thrombophilias have an increased risk of gestational
VTE independent of a positive family history of VTE. In contrast to current
guidelines, these data suggest that women with high-risk thrombophilia should be
considered for antenatal thromboprophylaxis regardless of family history of VTE.
PMID- 27613198
TI - Psychosocial challenges of xenotransplantation: the need for a multidisciplinary,
religious, and cultural dialogue.
PMID- 27613199
TI - Inconsistencies between 14C and short-lived radionuclides-based sediment
accumulation rates: Effects of long-term remineralization.
AB - 14C is the most widely utilized geochronometer to investigate geological,
geochemical and geophysical problems over the past 5 decades. Establishment of
precise sedimentation rates is crucial for the reconstruction of paleo-climate,
ecological and - environmental studies when extrapolation of sedimentation rates
is utilized for time scales beyond the dating range. However, agreement between
short-term and long-term sedimentation rates in anthropogenically unperturbed
sediment cores has not been shown. Here we show that the AMS 14C-based long-term
mass accumulation rate (MAR) of an organic-rich (>70%) sediment core from Mud
Lake, Florida to be ~5 times lower than the short-term MAR obtained using
239,240Pu, 137Cs and excess 210Pb (210Pbxs). The measured sediment inventories of
210Pbxs, 137Cs and 239,240Pu are comparable to the atmospheric fallout for the
sampling site, indicating very little accelerated sediment erosion over the past
several decades. Presence of sharp fallout peaks of 239,240Pu indicates very
little sediment mixing. The penetration depths of 137Cs and 239,240Pu were found
to be much deeper than expected and this is attributed to their post-depositional
mobility. MAR calculated using 14C-ages in successive layers also indicated
decreasing MARs with depth, and was reflective of progressive remineralization.
Using first-order kinetics, the sediment remineralization rate was found to be
4.4 * 10-4 y-1 and propose that over the long-term, remineralization of organic
rich sediment affected the long-term MAR, but not the ratio of 14C/12C. Thus, the
MAR and linear sedimentation rate obtained using 14C (and other isotope-based
methods) could be erroneous, although 14C ages may not be affected by such
remineralization. Long-term remineralization rates of organic matter has a direct
bearing on the biogeochemical cycling of elements in aqueous systems and mass
balance of elements needs to be taken into consideration.
PMID- 27613200
TI - Epigenetic mechanisms of macrophage activation in type 2 diabetes.
AB - The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous
strain on global healthcare systems. Over the past decade extensive research has
focused on the role of macrophages as key mediators of inflammation in T2D. The
inflammatory environment in the obese adipose tissue and pancreatic beta-cell
islets creates and perpetuates imbalanced inflammatory macrophage activation.
Consequences of this chronic low-grade inflammation include insulin resistance in
the adipose tissue and pancreatic beta-cell dysfunction. Recently, the emerging
field of epigenetics has provided new insights into the pathogenesis of T2D,
while also affording potential new opportunities for treatment. In macrophages,
epigenetic mechanisms are increasingly being recognized as crucial controllers of
their phenotype. Here, we first describe the role of macrophages in T2D. Then we
elaborate on epigenetic mechanisms that regulate macrophage activation, thereby
focusing on T2D. Next, we highlight how diabetic conditions such as
hyperlipidemia and hyperglycemia could induce epigenetic changes that promote an
inflammatory macrophage phenotype. In conclusion we discuss possible therapeutic
interventions by targeting macrophage epigenetics and speculate on future
research directions.
PMID- 27613201
TI - Optical Coherence Tomography Angiography of DME and Its Association with Anti
VEGF Treatment Response.
AB - PURPOSE: To investigate the structural integrity of the superficial capillary
plexuses (SCPs) and deep capillary plexuses (DCPs) using optical coherence
tomography (OCT) angiography (OCTA) in patients with diabetic macular edema (DME)
and its association with the response to anti-vascular endothelial growth factor
(VEGF) treatment. DESIGN: Retrospective, case-control study. PARTICIPANTS: We
included 51 DME eyes with a poor response to anti-VEGF agents and 32 age-matched
DME eyes with a good response to anti-VEGF treatment, along with 20 fellow eyes
without DME from the cases and controls. METHODS: The medical records, including
OCTA and spectral-domain OCT (SD OCT), were reviewed and compared between the
groups. En face OCTA images of the SCP and DCP were obtained for each eye. An
anti-VEGF responder was defined by a reduction of more than 50 MUm in central
retinal thickness after 3 consecutive anti-VEGF treatments. A poor responder was
defined by a reduction of less than 50 MUm or an increase in central retinal
thickness after 3 monthly injections. MAIN OUTCOME MEASURES: We measured the
vascular density and foveal avascular zone (FAZ) area and counted the number of
microaneurysms in each layer. The SD OCT images were compared with OCTA findings.
RESULTS: Compared with non-DME eyes, DME eyes had a lower vascular density (P <
0.001) and larger FAZ area (P < 0.001) in the DCP and more microaneurysms (P <
0.001) in both layers. Although there was no significant difference in the SCP
between anti-VEGF responders and poor responders, poor responders tended to show
greater damage and more microaneurysms in the DCP (P < 0.001) and a larger FAZ
area (P < 0.001). The topographic location of the disrupted synaptic portion of
the outer plexiform layer (OPL) in SD OCT exactly corresponded to the nonflow
area of the DCP in OCTA. CONCLUSIONS: Compared with DME eyes that responded to
anti-VEGF treatment, poor responders show significant damage to the integrity of
the DCP, but not the SCP. The degree of OPL disruption in SD OCT corresponds well
with the extent of DCP loss in DME eyes. The extent of DCP loss and the
corresponding OPL disruption could be useful predictors of responsiveness to anti
VEGF treatment.
PMID- 27613203
TI - 2014: A Record-Breaking Year for West Nile Virus Positive Mosquito Pools in
Harris County and the City of Houston, Texas.
AB - In the 14 years since the emergence of West Nile virus (WNV) in Harris County and
the city of Houston, Texas, the number of mosquitoes infected with the virus has
fluctuated with several high and low count years. During this 14-year period,
mosquito surveillance operational areas in Harris County were expanded from 248
to 268 and the distribution of the virus activity in mosquitoes varied from year
to year. Operational areas with WNV infected mosquitoes increased from 137 in
2002 to 197 in 2006, decreased to 71 areas in 2007, and to an all-time low of 18
in 2008. The number increased to 78 areas in 2009, 96 in 2010, 133 in 2011, and
177 in 2012, but fell to 73 in 2013. However, 234 areas were confirmed in 2014,
and only 138 in 2015. The WNV transmission was high in 2002 with 227 WNV positive
mosquito pools. The number of positive mosquitoes remained elevated for a number
of years and then declined from 2007 to 2010. Three record high years for WNV
activity were: 2005, 2006, and 2011 with 698, 838, and 605 confirmed positive
mosquito pools, respectively. Viral activity declined in 2012, followed by a
marked decline in 2013 with only 147 WNV positive mosquito pools. In 2014, a
record-breaking number of 1,286 WNV positive mosquito pools were confirmed in
Harris County and the city of Houston, the most ever in a single season, while
406 were confirmed in 2015.
PMID- 27613202
TI - Turkish university students' knowledge of biotechnology and attitudes toward
biotechnological applications.
AB - This study questions the presumed relation between formal schooling and
scientific literacy about biotechnologies. Comparing science and nonscience
majors' knowledge of and attitudes toward biotechnological applications,
conclusions are drawn if their formal learnings improve pupils' understandings of
and attitudes toward biotechnology applications. Sample of the study consists of
403 undergraduate and graduate students, 198 nonscience, and 205 science majors.
The Biotechnology Knowledge Questionnaire and the Biotechnology Attitude
Questionnaire were administered. Descriptive statistics (mean and percentages), t
test, and correlations were used to examine the participants' knowledge of
biotechnology and attitudes toward biotechnological applications and differences
as regards their majors. Although the science majors had higher knowledge and
attitude scores than the nonscience majors, it is not possible to say that they
have sufficient knowledge of biotechnologies. Besides, the participants'
attitudes toward biotechnological applications were not considerably related to
their knowledge of biotechnology. (c) 2016 by The International Union of
Biochemistry and Molecular Biology, 45(2):115-125, 2017.
PMID- 27613204
TI - A Multiagency Approach to Reducing West Nile Virus Risk in Richmond County,
Georgia, in 2015.
AB - The Richmond County Mosquito Control program's mission statement is to
incorporate strategies of integrated mosquito control management that are
effective, practical, and environmentally safe and protect the health of Richmond
County residents, as well as promote public education, in order to prevent large
mosquito populations and the diseases that they transmit. To this end, the
program coordinates efforts with other county agencies in order to provide better
service. This is a small program with limited resources, so in an effort to
provide better integrated mosquito management, the mosquito control program and
the Phinizy Center for Water Sciences joined efforts to trap mosquitoes at sites
across the county, identify the species, and send the mosquitoes off for viral
testing. These data help determine locations of disease-carrying mosquitoes so
the county can more efficiently control the mosquito populations and reduce the
risk of West Nile virus transmission.
PMID- 27613205
TI - Protection of Military Personnel Against Vector-Borne Diseases: A Review of
Collaborative Work of the Australian and US Military Over the Last 30 Years.
AB - Australian and US military medical services have collaborated since World War II
to minimize vector-borne diseases such as malaria, dengue, and scrub typhus. In
this review, collaboration over the last 30 years is discussed. The collaborative
projects and exchange scientist programs have resulted in mutually beneficial
outcomes in the fields of drug development and personal protection measures
against vector-borne diseases.
PMID- 27613206
TI - Emerging Tick-borne Rickettsia and Ehrlichia at Joint Base Langley-Eustis, Fort
Eustis, Virginia.
AB - Four species of ticks known to parasitize humans (Amblyomma americanum (lone star
tick), Dermacentor variabilis (American dog tick), Amblyomma maculatum (Gulf
Coast tick), and Ixodes scapularis (black-legged tick)) were collected at Joint
Base Langley-Eustis, Fort Eustis, Virginia during 2009. These ticks were tested
individually (adults and nymphs) and in pools of 15 (larvae) for pathogens of
public health importance within the genera: Rickettsia, Borrelia, and Ehrlichia,
by quantitative real-time polymerase chain reaction (qPCR) assays and, where
appropriate, multilocus sequence typing (MLST). Of the 340 A americanum ticks
tested, a minimum of 65 (19%), 4 (1%), 4 (1%), and one (<1%) were positive for
Rickettsia amblyommii, B lonestari, E ewingii and E chaffeensis, respectively.
One of 2 (50%) A maculatum ticks collected was found to be positive for R parkeri
by MLST and qPCR analyses. All 33 D variabilis ticks were negative for evidence
of rickettsial infections. Likewise, no pathogenic organisms were detected from
the single Ixodes scapularis tick collected. Pathogenic rickettsiae and
ehrlichiae are likely emerging and cause under-recognized diseases, which
threaten people who live, work, train, or otherwise engage in outdoor activities
at, or in the vicinity of, Fort Eustis, Virginia.
PMID- 27613207
TI - Honey Bee Swarms Aboard the USNS Comfort: Recommendations for Sting Prevention,
Swarm Removal, and Medical Readiness on Military Ships.
AB - The article provides observations of multiple honey bee (Apis mellifera) swarms
aboard the USNS Comfort (TAH-20) during the Continuing Promise 2015 mission. A
brief overview of swarming biology is given along with control/removal
recommendations to reduce sting exposures. The observations suggest that
preventive medicine personnel should provide adequate risk communications about
the potential occurrence of bee swarms aboard military ships, and medical
department personnel should be prepared for the possibility of treating of
multiple sting exposures, especially in the Southern Command Area of Operations
where the Africanized genotype of A mellifera is common.
PMID- 27613208
TI - Mortality From Fungal Diseases in the US Air Force From 1970 to 2013.
AB - We review a unique set of documents, death certificates, catalogued in the US Air
Force Mortality Registry, which tracks deaths for current and retired Air Force
service members. We screened the records for all deaths caused by fungal diseases
between 1970 and 2013. There were 216 deaths caused by a variety of diseases such
as aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis,
histoplasmosis, mucormycosis, pneumocystosis, sporotrichosis, and zygomycosis.
The single most common identified cause of death was opportunistic candidiasis.
Of the total 216 deaths, only 7 were active duty or active reserve personnel.
PMID- 27613209
TI - Does Reducing Time to Identification of Infectious Agents Reduce Incidence Rates
of Norovirus in a Population Deployed to Southwest Asia?
AB - During its deployment to Kuwait from 2011-2012, the 983rd Medical Detachment
(Preventive Medicine) was augmented with a 4-person laboratory section which
provided polymerase chain reaction capabilities not normally associated with an
Army Level III preventive medicine detachment. Although common in many civilian
laboratories, this was the first time this equipment was used by a deployed Level
III Army preventive medicine detachment to identify an outbreak in this theater.
It allowed rapid identification and description of a gastrointestinal disease
outbreak caused by norovirus in Kuwait. The technology contributed to a decreased
time required to identification of the causative agent (hours vs days) and thus
the implementation of appropriate preventive measures. Based on this event, the
authors suggest the addition of a modified laboratory section to the modified
table of organization equipment for deployable preventive medicine detachments.
PMID- 27613210
TI - Hearing Loss and Tinnitus in Military Personnel with Deployment-Related Mild
Traumatic Brain Injury.
AB - The objective of this study was to analyze differences in incidence and
epidemiologic risk factors for significant threshold shift (STS) and tinnitus in
deployed military personnel diagnosed with mild traumatic brain injury (mTBI) due
to either a blast exposure or nonblast head injury. A retrospective longitudinal
cohort study of electronic health records of 500 military personnel (456 met
inclusion criteria) diagnosed with deployment-related mTBI was completed. Chi
square tests and STS incidence rates were calculated to assess differences
between blast-exposed and nonblast groups; relative risks and adjusted odds
ratios of developing STS or tinnitus were calculated for risk factors. Risk
factors included such characteristics as mechanism of injury, age, race, military
occupational specialty, concurrent diagnosis of posttraumatic stress disorder
(PTSD), and nicotine use. Among blast-exposed and nonblast patients, 67% and 58%,
respectively, developed STS, (P=.06); 59% and 40%, respectively, developed
tinnitus (P<.001). Incidence of STS was 24% higher in the blast-exposed than
nonblast group. Infantry service was associated with STS; Marine Corps service,
PTSD, and zolpidem use were associated with tinnitus. Unprotected noise exposure
was associated with both STS and tinnitus. This study highlights potential risk
factors for STS and tinnitus among blast-exposed and nonblast mTBI patient
groups.
PMID- 27613211
TI - Going GLP: Conducting Toxicology Studies in Compliance with Good Laboratory
Practices.
AB - Good laboratory practice standards are US federal regulations enacted as part of
the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR Part 160), the
Toxic Substance Control Act (40 CFR Part 792), and the Good Laboratory Practice
for Nonclinical Laboratory Studies (21 CFR Part 58) to support protection of
public health in the areas of pesticides, chemicals, and drug investigations in
response to allegations of inaccurate data acquisition. Essentially, good
laboratory practices (GLPs) are a system of management controls for nonclinical
research studies involving animals to ensure the uniformity, consistency,
reliability, reproducibility, quality, and integrity of data collected as part of
chemical (including pharmaceuticals) tests, from in vitro through acute to
chronic toxicity tests. The GLPs were established in the United States in 1978 as
a result of the Industrial Bio-Test Laboratory scandal which led to congressional
hearings and actions to prevent fraudulent data reporting and collection.
Although the establishment of infrastructure for GLPs compliance is labor
intensive and time-consuming, achievement and maintenance of GLP compliance
ensures the accuracy of the data collected from each study, which is critical for
defending results, advancing science, and protecting human and animal health.
This article describes how and why those in the US Army Medical Department
responsible for protecting the public health of US Army and other military
personnel made the policy decision to have its toxicology laboratory achieve
complete compliance with GLP standards, the first such among US Army
laboratories. The challenges faced and how they were overcome are detailed.
PMID- 27613212
TI - An Expression of Change: Breastfeeding in the Military.
PMID- 27613214
TI - Bridging the Gap Between Burn Pits and Waste-to-Energy Technology: Safe and
Effective Waste Management in Contingency Operations.
PMID- 27613213
TI - Chemical Weapons Exposures in Iraq: Challenges of a Public Health Response a
Decade Later.
AB - An October 14, 2014 article in The New York Times reported that the US Department
of Defense (DoD) concealed, for nearly a decade, circumstances surrounding
service members' exposure to chemical warfare agents (CWA) while deployed to Iraq
in support of Operations Iraqi Freedom and New Dawn from March 13, 2003, to
December 31, 2011, and alleged failure of the DoD to provide expedient and
adequate medical care. This report prompted the DoD to devise a public health
investigation, with the Army Public Health Center (Provisional) as the lead
agency to identify, evaluate, document, and track CWA casualties of the Iraq war.
Further, the DoD revisited and revised clinical guidelines and health policies
concerning CWA exposure based on current evidence-based guidelines and best
practices.
PMID- 27613215
TI - Animal-Assisted Health and the Performance Triad.
PMID- 27613216
TI - Service Animals: A New Legal Dimension Within the US Military.
PMID- 27613217
TI - Grace Under Fire: The Army Nurses of Pearl Harbor, 1941.
AB - OBJECTIVE: Much has been written about the military events of December 7, 1941;
however, little has been documented about the nurses' work and experience at
Pearl Harbor, Hawaii. The aerial assault on Pearl Harbor was the first time in US
history that Army nurses had been on the front line of battle. Nurses quickly
triaged and stabilized those who could be saved, and provided compassion and
comfort to those who were dying, in an environment where the nurses were unsure
of their own survival. METHODS: Traditional historical methods and a social
history framework were used in this investigation. Primary sources included oral
histories from the US Army Medical Department Center of History and Heritage and
the State of Hawaii's website, Hawaii Aviation. Secondary sources included
published books, newspaper articles, military websites, and history texts.
RESULTS: Due to the limited bed capacity, Hickam Field Hospital converted to an
evacuation hospital. Nurses, physicians, and medical corpsman triaged,
stabilized, and transported those likely to survive, while staging the dead
behind the building. The emergency room at Tripler Hospital was quickly flooded
with patients from the battlefield, but the staff was able to sort patients
appropriately to the wards, to the operating room, or provide comfort care as
they died. At Schofield Hospital, collaboration between tireless doctors, nurses,
and corpsmen was key to providing life-saving surgery and care.
PMID- 27613218
TI - Military Medicine of the Russo-Japanese War and its Influence on the
Modernization of the US Army Medical Department.
PMID- 27613219
TI - Involved, United, and Efficacious: Could Self-Affirmation Be the Solution to
California's Drought?
AB - Self-affirmation theory posits that thoughts and actions that affirm an important
aspect of the self-concept can make people more susceptible to change by casting
their self in a positive light. Whereas much of the current literature has been
restricted to individual-level concerns, the current study provides longitudinal
evidence for behavioral outcomes in the context of the California drought,
advancing our theoretical knowledge regarding the underlying processes that lead
self-affirmed individuals to address societal risks and collective concerns. The
results of a three-wave experimental study (N = 91) indicated that relative to
nonaffirmed counterparts, self-affirmed participants reported on higher levels of
support for water conservation policies, as well as on reduction of water use
that endured for 30 days following the self-affirming manipulation. In both
cases, the effects were mediated by collective-efficacy but not by self-efficacy.
Relevant explanations are considered and practical and theoretical implications
are discussed.
PMID- 27613220
TI - Characterization of Young Adult Emergency Department Users: Evidence to Guide
Policy.
AB - PURPOSE: The purpose of this study was to characterize young adult patients aged
19-25 years who are emergency department (ED) frequent users and study factors
associated with frequent ED use. METHODS: ED visits among 19- to 25-year olds
were identified from administrative records in California, Florida, Iowa,
Massachusetts, and New York, 2010. Patients were analyzed for 12 months to study
the frequency of their ED utilization. ED visits were categorized according to
primary diagnosis. Patients were stratified by frequency of ED use: one visit
(single users), two to four visits (infrequent users), and five or more visits
(frequent users) in a 1-year period. RESULTS: We identified 1,711,774 young adult
patients who made 3,650,966 ED visits. Sixty-six percent of patients were single
users, 29% were infrequent users, and 4.6% were frequent users. Frequent users
accounted for a disproportionate 28.8% of visits within the population studied.
Frequent users had the largest proportion of visits for complications of
pregnancy (13.6%) compared to single users (6.1%) and Medicaid (42.6%) compared
to private insurance (17.3%). There was an increased risk of frequent ED use
associated with females (odds ratio [OR]: 1.77), Medicaid (OR: 3.21), and
Medicare insurance (OR: 4.22) compared to private insurance, and diseases of the
blood (OR: 3.36) and mental illness (OR: 1.99) compared to injury and poisoning.
CONCLUSIONS: Frequent users comprise a significant portion of the young adult ED
population and present with a large proportion of visits for complications of
pregnancy. Policies targeting this population might focus on improved access to
primary and urgent care, acute obstetric care, and better coordination of care.
PMID- 27613222
TI - The effect of health and dental insurance on US children's dental care
utilization for urgent and non-urgent dental problems - 2008.
AB - OBJECTIVE: We examined the association between utilization of care for a dental
problem (utilization-DP) and parent-reported dental problem (DP) urgency among
children with DP by type of health care insurance coverage. METHODS: We used
weighted 2008 National Health Interview Survey data from 2,834 children, aged 2
17 years with at least one DP within the 6 months preceding survey. Explanatory
variables were selected based on Andersen's model of healthcare utilization. Need
was considered urgent if DP included toothache, bleeding gums, broken or missing
teeth, broken or missing filling, or decayed teeth and otherwise as non-urgent.
The primary enabling variable, insurance, had four categories: none, private
health no dental coverage (PHND), private health and dental (PHD), or
Medicaid/State Children's Health Insurance Program (SCHIP). Predisposing
variables included sociodemographic characteristics. We used bivariate and
multivariate analyses to identify explanatory variables' association with
utilization-DP. Using logistic regression, we obtained adjusted estimates of
utilization-DP by urgency for each insurance category. RESULTS: In bivariate
analyses, utilization-DP was associated with both insurance and urgency. In
multivariate analyses, the difference in percent utilizing care for an urgent
versus non-urgent DP among children covered by Medicaid/SCHIP was 32 percentage
points; PHD, 25 percentage points; PHND, 12 percentage points; and no insurance,
14 percentage points. The difference in utilization by DP urgency was higher for
children with Medicaid/SCHIP compared with either PHND or uninsured children.
CONCLUSION: Expansion of Medicaid/SCHIP may permit children to receive care for
urgent DPs who otherwise may not, due to lack of dental insurance.
PMID- 27613221
TI - The Green Tetrahymena utriculariae n. sp. (Ciliophora, Oligohymenophorea) with
Its Endosymbiotic Algae (Micractinium sp.), Living in Traps of a Carnivorous
Aquatic Plant.
AB - The genus Tetrahymena (Ciliophora, Oligohymenophorea) probably represents the
best studied ciliate genus. At present, more than forty species have been
described. All are colorless, i.e. they do not harbor symbiotic algae, and as
aerobes they need at least microaerobic habitats. Here, we present the
morphological and molecular description of the first green representative,
Tetrahymena utriculariae n. sp., living in symbiosis with endosymbiotic algae
identified as Micractinium sp. (Chlorophyta). The full life cycle of the ciliate
species is documented, including trophonts and theronts, conjugating cells,
resting cysts and dividers. This species has been discovered in an exotic
habitat, namely in traps of the carnivorous aquatic plant Utricularia reflexa
(originating from Okavango Delta, Botswana). Green ciliates live as commensals of
the plant in this anoxic habitat. Ciliates are bacterivorous, however, symbiosis
with algae is needed to satisfy cell metabolism but also to gain oxygen from
symbionts. When ciliates are cultivated outside their natural habitat under
aerobic conditions and fed with saturating bacterial food, they gradually become
aposymbiotic. Based on phylogenetic analyses of 18S rRNA and mitochondrial cox1
genes T. utriculariae forms a sister group to Tetrahymena thermophila.
PMID- 27613223
TI - Downstream effect profiles discern different mechanisms of integrin alphaLbeta2
inhibition.
AB - The integrin leucocyte function-associated antigen-1 (alphaLbeta2, LFA-1) plays
crucial roles in T cell adhesion, migration and immunological synapse (IS)
formation. Consequently, alphaLbeta2 is an important therapeutic target in
autoimmunity. Three major classes of alphaLbeta2 inhibitors with distinct modes
of action have been described to date: Monoclonal antibodies (mAbs), small
molecule alpha/beta I allosteric and small molecule alpha I allosteric
inhibitors. The objective of this study was to systematically compare these three
modes of alphaLbeta2 inhibition for their alphaLbeta2 inhibitory as well as their
potential agonist-like effects. All inhibitors assessed were found to potently
block alphaLbeta2-mediated leucocyte adhesion. None of the inhibitors induced
ZAP70 phosphorylation, indicating absence of agonistic outside-in signalling.
Paradoxically, however, the alpha/beta I allosteric inhibitor XVA143 induced
conformational changes within alphaLbeta2 characteristic for an intermediate
affinity state. This effect was not observed with the alpha I allosteric
inhibitor LFA878 or the anti-alphaLbeta2 mAb efalizumab. On the other hand,
efalizumab triggered the unscheduled internalization of alphaLbeta2 in CD4+ and
CD8+ T cells while LFA878 and XVA143 did not affect or only mildly reduced
alphaLbeta2 surface expression, respectively. Moreover, efalizumab, in contrast
to the small molecule inhibitors, disturbed the fine-tuned
internalization/recycling of engaged TCR/CD3, concomitantly decreasing ZAP70
expression levels. In conclusion, different modes of alphaLbeta2 inhibition are
associated with fundamentally different biologic effect profiles. The
differential established here is expected to provide important translational
guidance as novel alphaLbeta2 inhibitors will be advanced from bench to bedside.
PMID- 27613224
TI - Spatiotemporal study of elderly suicide in Korea by age cohort.
AB - OBJECTIVES: This study analyzed the spatiotemporal pattern and spatial diffusion
of elderly suicide by age cohort, in Korea. STUDY DESIGN: The research
investigated the elderly suicide rates of the 232 municipal units in South Korea
between 2001 and 2011. METHODS: The Gi* score, which is a spatially weighted
indicator of area attributes, was used to identify hot spots and the
spatiotemporal pattern of elderly suicide in the nation during the last 10 years.
The spatial Markov matrix and spatial dynamic panel data model were employed to
identify and estimate the diffusion effect. RESULTS: The suicide rate among
elderly individuals 75 years and older was substantially higher than the rate for
those between 65 and 74 years of age; however, the spatial patterns of the
suicide clusters were similar between the two groups. From 2001 to 2011, the
spatial distribution of elderly suicide hot spots differed each year. For both
age cohorts, elderly suicide hot spots developed around the north area of South
Korea in 2001 and moved to the mid-east area and the mid-western coastal area
over 10 years. The spatial Markov matrix indicates that the change in the suicide
rate of one area was affected by the suicide rates of neighbouring areas from the
previous year, which suggests that suicide increase in one area inflates a
neighbouring area's suicide rate over time. Using a spatial dynamic panel data
model, elderly suicide diffusion effects were found to be statistically
significant for both age cohorts even after economic and demographic indicators
and a time variable are included. For individuals 75 years and older, the
diffusion effect appeared to be larger. CONCLUSIONS: This study demonstrates that
elderly suicide can spread spatially over time in both age cohorts. Thus, it is
necessary to design a place-based and age-differentiated intervention policy that
precisely considers the spatial diffusion of elderly suicide.
PMID- 27613225
TI - Risk factors for severe acute malnutrition in under-five children: a case-control
study in a rural part of India.
AB - OBJECTIVES: The present study was planned to identify some of the risk factors of
severe acute malnutrition (SAM) in under-five children in a rural part of India.
STUDY DESIGN: Case-control study. METHODS: The study was carried out in rural
areas of Yavatmal district. A total of 737 cases (under-five SAM children) and an
equal number of normal controls were included in the study. Data were collected
using a structured questionnaire. Binary logistic regression was used for
multivariate analysis using a hierarchical model. RESULTS: The odds of a child
being in the SAM category increased significantly if the family: was below the
poverty line, have a kuccha house, have more children in the family, have less
rooms in the house, have a working mother, has a mother with a lower level of
education, have an unemployed father, did not use any water purification measure,
did not always ensure parents washed their hands before feeding a child, did not
wash hands with soap and water after defecation, have a father with any addictive
habit like tobacco or alcohol consumption, have a maternal height <145 cm, have a
maternal weight <45 kg, have a lower age at marriage for mothers, had an
institutional delivery, have the same food utilized more than once in a day, have
no age-appropriate vaccination, give prelacteal feeds, have a lower frequency of
breast feeding, do not use semisolid food during the weaning period, exclusively
breast feed for less than four months or more than six months, had low birth
weight, have five or more episodes of illness in the previous year, have <=3
feeds per day apart from breast milk, and not initiation of breast feeding within
30 min of birth. CONCLUSION: Risk factors identified in the present study can be
addressed through health system interventions. The strongest association was
observed with child feeding practices; thus, more emphasis is required in
nutritional education and counselling in strategies to fight undernutrition.
PMID- 27613226
TI - Molecular drivers of mitochondrial membrane proliferation in response to cold
acclimation in threespine stickleback.
AB - Little is known about how the synthesis of mitochondrial phospholipids is
integrated into mitochondrial biogenesis in fish or mammals. Glycerol-3-phosphate
acyltransferase (GPAT; EC 2.3.1.15) catalyzes the addition of fatty acyl CoA to
the sn-1 position of glycerol-3-phosphate, in what is considered the rate
limiting step in phospholipid biosynthesis. Previous studies have shown that
mitochondrial volume density increases in oxidative skeletal muscle but not liver
of Gasterosteus aculeatus (threespine stickleback) in response to cold
acclimation. We hypothesized that maximal activity of GPAT would increase in
oxidative skeletal muscle but not liver during cold acclimation, coinciding with
mitochondrial biogenesis. GPAT activity was measured in liver and oxidative
skeletal (pectoral adductor) muscle of threespine stickleback acclimated to 8
degrees C or 20 degrees C. In addition, mRNA levels of enzymes involved in
phospholipid synthesis, including cytidine diphosphodiacylglycerol synthase-1
(CDS1), CDS2, GPAT1, GPAT2 and 1-acylglycerol 3-phosphate acyltransferase-2
(AGPAT2), were quantified in liver and pectoral muscle of stickleback harvested
during cold acclimation. GPAT activity and transcript levels of AGPAT2 increased
in response to cold acclimation in pectoral muscle but not liver. Transcript
levels of GPAT1 increased in liver but not pectoral muscle. Overall our results
suggest that the activity of GPAT, and possibly AGPAT as well, increase during
cold acclimation and may contribute to mitochondrial phospholipid biosynthesis
required for mitochondrial biogenesis.
PMID- 27613227
TI - Actinomyces succiniciruminis sp. nov. and Actinomyces glycerinitolerans sp. nov.,
two novel organic acid-producing bacteria isolated from rumen.
AB - Two bacterial strains, Am4 and G10 were isolated from rumen fluid of different
ruminants: cow (Holstein-Friesian) and sheep (Slovenske merino), respectively.
They were isolated from different hosts and regions, but showed 99.2% similarity
of the 16S rRNA genes. Both strains are versatile and ferment various sugars to
mainly succinate and lactate and small amounts of acetate and formate. The 16S
rRNA sequences of Am4 and G10 revealed that they belonged to the genus
Actinomyces, and are related to Actinomyces ruminicola JCM 13352T with 97.0% and
97.4% similarity, respectively. DDH showed strain Am4 and G10 had only 55.8 and
43.3% similarity with the Actinomyces ruminicola JCM 13352T, and had 69.9%
similarity among each other. Comparing strain Am4 and G10, gANI value and dDDH
were 92.9% and 68.6%, respectively. Additionally, AAI between the strains was
95.8%. MLSA of housekeeping genes showed difference of metG and pheS. The G+C%
contents of strain Am4 and G10 were 69.8% and 68.5%, respectively. MK-10(H4) was
the principal quinone for strain Am4 (82%) and G10 (91%) with small amounts of MK
10(H8) and MK-10(H6) for both strains. Only MK-9(H4) was detected in strain Am4.
MALDI-TOF analysis of protein profiles also revealed that Am4 and G10 are
different from each other and from Actinomyces ruminicola JCM 13352T. Based on
phylogenetic and physiological characteristics, together with genome comparison
and MLSA we propose two novel species in the genus Actinomyces: Actinomyces
succiniciruminis sp. nov. (type strain Am4T=TISTR 2317T=DSM 10376T) and
Actinomyces glycerinitolerans sp. nov. (type strain G10T=TISTR 2318T=DSM 10377T).
PMID- 27613228
TI - The Effects of Maternal Under-Nutrition and a Post-Natal High Fat Diet on Lens
Growth, Transparency and Oxidative Defense Systems in Rat Offspring.
AB - PURPOSE: A poor early life nutrition environment is well established to result in
a range of cardiometabolic disorders in offspring in later life. These effects
can be exacerbated via exposure to an obesogenic dietary environment. To date,
the effect of maternal diet and/or a post-natal obesogenic nutritional
environment on key characteristics related to lens growth and oxidative stress
has not been undertaken. The present study, therefore, examined the
characteristics and oxidative status of the lens. MATERIALS AND METHODS: Using a
model of moderate maternal under-nutrition, rat dams were fed either a control
diet (100% ad libitum, CON) or undernourished throughout pregnancy (50% of ad
libitum intake, UN) and offspring fed either a control (5% fat, C) or high fat
(30% fat, HF) diet post-weaning, resulting in four nutritional groups; CON-C, CON
HF, UN-C, and UN-HF. Offspring lenses were extracted at 160 days of age, weighed,
imaged under dark and bright field microscopy, and then dissected into cortical
and core fractions for biochemical analyses of oxidative stress markers. RESULTS:
Our findings reveal that lenses from all groups were transparent. However, gender
specific changes were evident at the biochemical level with increased oxidative
stress detected in the cortex and core of female but not male UN-C lenses, and in
the cortex of male but not female CON-HF lenses. The greatest increase in
oxidative stress was detected in the UN-HF group in the cortex and core regions
of the lens and for both genders. CONCLUSIONS: These findings show that oxidative
stress is exacerbated in the lens as a result of a combination of altered pre
natal and post-natal diet. This demonstrates a novel interaction between the two
developmental windows and warrants further investigations toward devising
appropriate nutritional strategies for minimizing oxidative stress in the lens.
PMID- 27613229
TI - The neural basis of responsive caregiving behaviour: Investigating temporal
dynamics within the parental brain.
AB - Whether it is the sound of a distressed cry or the image of a cute face, infants
capture our attention. Parents and other adults alike are drawn into interactions
to engage in play, nurturance and provide care. Responsive caregiving behaviour
is a key feature of the parent-infant relationship, forming the foundation upon
which attachment is built. Infant cues are considered to be 'innate releasers' or
'motivational entities' eliciting responses in nearby adults (Lorenz 1943;
Murray, 1979) [42,43]. Through the advent of modern neuroimaging, we are
beginning to understand the initiation of this motivational state at the
neurobiological level. In this review, we first describe a current model of the
'parental brain', based on functional MRI studies assessing neural responses to
infant cues. Next, we discuss recent findings from temporally sensitive
techniques (magneto- and electroencephalography) that illuminate the temporal
dynamics of this neural network. We focus on converging evidence highlighting a
specific role for the orbitofrontal cortex in supporting rapid orienting
responses to infant cues. In addition, we consider to what extent these neural
processes are tied to parenthood, or whether they might be present universally in
all adults. We highlight important avenues for future research, including
utilizing multiple levels of analysis for a comprehensive understanding of
adaptive caregiving behaviour. Finally, we discuss how this research can help us
understand disrupted parent-infant relationships, such as in situations where
parents' contingent responding to infant cues is disrupted; for example, in
parental depression or anxiety where cognitive attentional processes are
disrupted.
PMID- 27613230
TI - Microglia depletion in early life programs persistent changes in social, mood
related, and locomotor behavior in male and female rats.
AB - Microglia, the innate immune cells of the central nervous system, regulate brain
development by promoting cell genesis, pruning synapses, and removing dying,
newly-born or progenitor cells. However, the role of microglia in the early life
programming of behavior under normal conditions is not well characterized. We
used central infusion of liposomal clodronate to selectively deplete microglia
from the neonatal rat brain and subsequently assessed the impact of microglial
depletion on programming of juvenile and adult motivated behaviors. Liposomal
clodronate treatment on postnatal days one and four led to greater than 70% loss
of forebrain microglia by postnatal day 6 that lasted for approximately ten days.
Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior
on the elevated plus maze and open field test, and increased locomotor activity.
On a test of juvenile social play, microglial depletion led to decreased chase
behaviors relative to control animals. There was no change in active social
behavior in adults on a reciprocal social interaction test, but there was
decreased passive interaction time and an increased number of social avoidance
behaviors in clodronate treated rats relative to controls. There was an overall
decrease in behavioral despair on the forced swim test in adult rats treated
neonatally with clodronate. Females, but not males, treated neonatally with
clodronate showed a blunted corticosterone response after acute stress in
adulthood. These results show that microglia are important for the early life
programming of juvenile and adult motivated behavior.
PMID- 27613231
TI - Use of Web 2.0 Social Media Platforms to Promote Community-Engaged Research
Dialogs: A Preliminary Program Evaluation.
AB - BACKGROUND: Community-engaged research is defined by the Institute of Medicine as
the process of working collaboratively with groups of people affiliated by
geographic proximity, special interests, or similar situations with respect to
issues affecting their well-being. Traditional face-to-face community-engaged
research is limited by geographic location, limited in resources, and/or uses one
way communications. Web 2.0 technologies including social media are novel
communication channels for community-engaged research because these tools can
reach a broader audience while promoting bidirectional dialogs. OBJECTIVE: This
paper reports on a preliminary program evaluation of the use of social media
platforms for promoting engagement of researchers and community representatives
in dialogs about community-engaged research. METHODS: For this pilot program
evaluation, the Clinical and Translational Science Office for Community
Engagement in Research partnered with the Social Media Network at our institution
to create a WordPress blog and Twitter account. Both social media platforms were
facilitated by a social media manager. We used descriptive analytics for
measuring engagement with WordPress and Twitter over an 18-month implementation
period during 2014-2016. For the blog, we examined type of user (researcher,
community representative, other) and used content analysis to generate the major
themes from blog postings. For use of Twitter, we examined selected demographics
and impressions among followers. RESULTS: There were 76 blog postings observed
from researchers (48/76, 64%), community representatives (23/76, 32%) and funders
(5/76, 8%). The predominant themes of the blog content were research awareness
and dissemination of community-engaged research (35/76, 46%) and best practices
(23/76, 30%). For Twitter, we obtained 411 followers at the end of the 18-month
evaluation period, with an increase of 42% (from 280 to 411) over the final 6
months. Followers reported varied geographic location (321/411, 78%, resided in
the United States); 99% (407/411) spoke English; and about half (218/411, 53%)
were female. Followers produced 132,000 Twitter impressions. CONCLUSIONS:
Researchers and community stakeholders use social medial platforms for dialogs
related to community-engaged research. This preliminary work is novel because we
used Web 2.0 social media platforms to engage these stakeholders whereas prior
work used face-to-face formats. Future research is needed to explore additional
social media platforms; expanded reach to other diverse stakeholders including
patients, providers, and payers; and additional outcomes related to engagement.
PMID- 27613234
TI - Peptococcus simiae sp. nov., isolated from rhesus macaque faeces and emended
description of the genus Peptococcus.
AB - A study of the faecal microbiome in three healthy female rhesus macaques revealed
the presence of a novel obligately anaerobic, chemoorganoheterotrophic, non
sporing, coccoid, non-motile, Gram-stain-positive bacterial species. Three
strains of this species, designated as M108T, M916-1/1, and M919-2/1, were non
haemolytic, H2S-positive, catalase-positive, bile- and NaCl-sensitive and
required peptone for growth. Strains also were asaccharolytic, able to utilize
sulfite, thiosulfate and elemental sulfur as electron acceptors, and produced
acetic and butyric acids as metabolic end-products. Strain M108T is characterized
by the prevalence of C14 : 0, C16 : 0 and C18 : 1omega9cis dimethyl acetal among
the cellular fatty acids, and the presence of MK-10 menaquinone. The DNA G+C
content was found to be 51 mol%. Phylogenetic analysis of partial 16S rRNA gene
sequences of strains M108T, M916-1/1 and M919-2/1 placed these strains into the
genus Peptococcus (family Peptococcaceae). On the basis of phenotypic and
genotypic properties we conclude that these strains represent a novel bacterial
species for which the name Peptococcus simiae sp. nov. is proposed. The type
strain is M108T (=DSM 100347T=VKM B-2932T).
PMID- 27613232
TI - In utero alcohol effects on foetal, neonatal and childhood lung disease.
AB - Maternal alcohol use during pregnancy exposes both premature and term newborns to
the toxicity of alcohol and its metabolites. Foetal alcohol exposure adversely
effects the lung. In contrast to the adult "alcoholic lung" phenotype, an
inability to identify the newborn exposed to alcohol in utero has limited our
understanding of its effect on adverse pulmonary outcomes. This paper will review
advances in biomarker development of in utero alcohol exposure. We will highlight
the current understanding of in utero alcohol's toxicity to the developing lung
and immune defense. Finally, we will present recent clinical evidence describing
foetal alcohol's association with adverse pulmonary outcomes including
bronchopulmonary dysplasia, viral infections such as respiratory syncytial virus
and allergic asthma/atopy. With research to define alcohol's effect on the lung
and translational studies accurately identifying the exposed offspring, the full
extent of alcohol's effects on clinical respiratory outcomes of the newborn or
child can be determined.
PMID- 27613235
TI - Type I interferon responses are impaired in latently HIV infected cells.
AB - BACKGROUND: The latent HIV-1 reservoir represents the primary barrier to the
eradication of HIV-1 infection. The design of novel reservoir-clearance
strategies, however, is impeded in part by the inability to distinguish latently
HIV-infected cells from uninfected cells. Significant impairment of the type I
interferon (IFN-I) response is observed during productive HIV-1 infection.
Although this remains poorly described in the context of latent HIV-1 infection,
presence of potential defects may serve as a novel therapeutic target. Therefore,
IFN-I pathways were characterized using two latently HIV-1-infected cell lines,
U1 and OM10.1, in comparison to their respective uninfected parental U937 and
HL60 cell lines. FINDINGS: Constitutive expression and induction of important
mediators of IFN-I signaling including IFNalpha/beta cytokines, IFNAR1, MHC-I,
ISG15, and PKR were evaluated following exogenous IFNalpha or poly(I:C)
treatment. Differences in basal expression of IFNAR1, MHC-I, and PKR were
observed between the latently HIV-1 infected and uninfected cell lines. In
parallel, significant impairments in the induction of MHC-I, ISG15 and PKR, as
well as secretion of IFNalpha/beta cytokines were observed in response to
appropriate exogenous stimulation within the two latently HIV-infected U1 and
OM10.1 cells, relative to their HIV-uninfected parental cells. CONCLUSIONS: In
comparison to the HIV-uninfected U937 and HL60 cell lines, widespread defects in
IFN-I responsiveness were observed within the latently HIV-infected U1 and OM10.1
cells. These impairments represent novel therapeutic targets, which may be
amenable to strategies currently employed in cancer therapy.
PMID- 27613233
TI - Neighbourhood walkability and home neighbourhood-based physical activity: an
observational study of adults with type 2 diabetes.
AB - BACKGROUND: Converging international evidence suggests that diabetes incidence is
lower among adults living in more walkable neighbourhoods. The association
between walkability and physical activity (PA), the presumed mediator of this
relationship, has not been carefully examined in adults with type 2 diabetes. We
investigated the associations of walkability with total PA occurring within home
neighbourhoods and overall PA, irrespective of location. METHODS: Participants (n
= 97; 59.5 +/- 10.5 years) were recruited through clinics in Montreal (QC,
Canada) and wore a GPS-accelerometer device for 7 days. Total PA was expressed as
the total Vector of the Dynamic Body Acceleration. PA location was determined
using a Global Positioning System (GPS) device (SIRF IV chip). Walkability
(street connectivity, land use mix, population density) was assessed using
Geographical Information Systems software. The cross-sectional associations
between walkability and location-based PA were estimated using robust linear
regressions adjusted for age, body mass index, sex, university education, season,
car access, residential self-selection, and wear-time. RESULTS: A one standard
deviation (SD) increment in walkability was associated with 10.4 % of a SD
increment in neighbourhood-based PA (95 % confidence interval (CI) 1.2, 19.7) -
equivalent to 165 more steps/day (95 % 19, 312). Car access emerged as an
important predictor of neighbourhood-based PA (Not having car access: 38.6 % of a
SD increment in neighbourhood-based PA, 95 % CI 17.9, 59.3). Neither walkability
nor car access were conclusively associated with overall PA. CONCLUSIONS: Higher
neighbourhood walkability is associated with higher home neighbourhood-based PA
but not with higher overall PA. Other factors will need to be leveraged to
facilitate meaningful increases in overall PA among adults with type 2 diabetes.
PMID- 27613236
TI - Mycobacterium tuberculosis and Mycobacterium marinum non-homologous end-joining
proteins can function together to join DNA ends in Escherichia coli.
AB - Mycobacterium tuberculosis and Mycobacterium smegmatis express a Ku protein and a
DNA ligase D and are able to repair DNA double strand breaks (DSBs) by non
homologous end-joining (NHEJ). This pathway protects against DNA damage when
bacteria are in stationary phase. Mycobacterium marinum is a member of this
mycobacterium family and like M. tuberculosis is pathogenic. M. marinum lives in
water, forms biofilms and infects fish and frogs. M. marinum is a biosafety level
2 (BSL2) organism as it can infect humans, although infections are limited to the
skin. M. marinum is accepted as a model to study mycobacterial pathogenesis, as
M. marinum and M. tuberculosis are genetically closely related and have similar
mechanisms of survival and persistence inside macrophage. The aim of this study
was to determine whether M. marinum could be used as a model to understand M.
tuberculosis NHEJ repair. We identified and cloned the M. marinum genes encoding
NHEJ proteins and generated E. coli strains that express the M. marinum Ku (Mm
Ku) and ligase D (Mm-Lig) individually or together (LHmKumLig strain) from
expression vectors integrated at phage attachment sites in the genome. We
demonstrated that Mm-Ku and Mm-Lig are both required to re-circularize Cla I
linearized plasmid DNA in E. coli. We compared repair of strain LHmKumLig with
that of an E. coli strain (BWKuLig#2) expressing the M. tuberculosis Ku (Mt-Ku)
and ligase D (Mt-Lig), and found that LHmKumLig performed 3.5 times more repair
and repair was more accurate than BWKuLig#2. By expressing the Mm-Ku with the Mt
Lig, or the Mt-Ku with the Mm-Lig in E. coli, we have shown that the NHEJ
proteins from M. marinum and M. tuberculosis can function together to join DNA
DSBs. NHEJ repair is therefore conserved between the two species. Consequently,
M. marinum is a good model to study NHEJ repair during mycobacterial
pathogenesis.
PMID- 27613237
TI - Copper chelation by trientine dihydrochloride inhibits liver RFA-induced
inflammatory responses in vivo.
AB - OBJECTIVE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the
third most common cause of cancer-related death worldwide. Radiofrequency
ablation (RFA) is currently performed widely for managing HCC. RFA treatment
causes damage around the ablation. Trientine dihydrochloride has been used to
reduce the copper in liver. METHODS: The rats were treated with trientine
dihydrochloride for 5 days before liver RFA. Liver function, copper
concentration, inflammation biomarkers and MDA, SOD were analyzed after RFA
treatment for 2 h, 2 and 5 days. RESULTS: The results indicated that trientine
dihydrochloride reduced the copper in plasma and liver tissue significantly. And
trientine dihydrochloride significantly inhibited RFA-induced inflammatory gene
expression in liver. Similar inhibitory effects of trientine dihydrochloride were
observed on ROS-induced malondialdehyde production in liver tissues. CONCLUSION:
These results suggest that pre-treatment with the selective copper chelator
trientine dihydrochloride can inhibit inflammatory response effectively during
and after liver RFA in vivo. Chelation of copper to a lower level before liver
RFA may be a novel strategy to prevent or ameliorate inflammatory responses in
liver induced by RFA and to protect the parenchyma tissues in liver during and
after RFA in HCC patients.
PMID- 27613238
TI - Use of MALDI-TOF MS and culturomics to identify mosquitoes and their midgut
microbiota.
AB - BACKGROUND: Mosquitoes transmit a wide range of human parasitic and viral
diseases. In recent years, new techniques such as MALDI-TOF MS have been
developed to identify mosquitoes at the species level, which is key for
entomological surveys. Additionally, there is increasing interest in the mosquito
microbiota and its role in vector capacity. METHODS: The culturomics approach
previously used in our laboratory to study human gut microbiota was applied to
evaluate the midgut bacterial diversity of Anopheles gambiae (wild and laboratory
strains), Aedes albopictus (wild and laboratory strains) and Culex
quinquefasciatus (wild strains) in order to determine the influence of the
environmental status on the midgut microbiota of the mosquitoes. RESULTS:
Mosquitoes collected in the field were accurately identified by MALDI-TOF MS
analysis of their legs. Adult mosquito midgut microbiota was composed of four
phyla, including Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes.
The majority of the bacteria detected in the microbiota of mosquitoes were gram
negative and belong to the phylum Proteobacteria. MALDI-TOF MS identified for the
first time a new bacterial species from An. gambiae midgut microbiota.
CONCLUSION: In this study, the culturomics approach was found to be a reliable
technique for exploring the diversity of the mosquito microbiota. MALDI-TOF MS
was confirmed as a promising technique to identify mosquitoes collected in the
field. Culturomics allowed the isolation of a new bacterial species not
previously associated with mosquito vectors. The environment plays a role in the
bacterial diversity of the microbiota, which could enable the development of new
control strategies for mosquito-borne disease.
PMID- 27613239
TI - Comparison of different approaches applied in Analytic Hierarchy Process - an
example of information needs of patients with rare diseases.
AB - BACKGROUND: The Analytic Hierarchy Process (AHP) is increasingly used to measure
patient priorities. Studies have shown that there are several different
approaches to data acquisition and data aggregation. The aim of this study was to
measure the information needs of patients having a rare disease and to analyze
the effects of these different AHP approaches. The ranking of information needs
is then used to display information categories on a web-based information portal
about rare diseases according to the patient's priorities. METHODS: The
information needs of patients suffering from rare diseases were identified by an
Internet research study and a preliminary qualitative study. Hence, we designed a
three-level hierarchy containing 13 criteria. For data acquisition, the
differences in outcomes were investigated using individual versus group
judgements separately. Furthermore, we analyzed the different effects when using
the median and arithmetic and geometric means for data aggregation. A consistency
ratio <=0.2 was determined to represent an acceptable consistency level. RESULTS:
Forty individual and three group judgements were collected from patients
suffering from a rare disease and their close relatives. The consistency ratio of
31 individual and three group judgements was acceptable and thus these judgements
were included in the study. To a large extent, the local ranks for individual and
group judgements were similar. Interestingly, group judgements were in a
significantly smaller range than individual judgements. According to our data,
the ranks of the criteria differed slightly according to the data aggregation
method used. CONCLUSIONS: It is important to explain and justify the choice of an
appropriate method for data acquisition because response behaviors differ
according to the method. We conclude that researchers should select a suitable
method based on the thematic perspective or investigated topics in the study.
Because the arithmetic mean is very vulnerable to outliers, the geometric mean
and the median seem to be acceptable alternatives for data aggregation. Overall,
using the AHP to identify patient priorities and enhance the user-friendliness of
information websites offers an important contribution to medical informatics.
PMID- 27613240
TI - Phylogeography of Diptychus maculatus (Cyprinidae) endemic to the northern margin
of the QTP and Tien Shan region.
AB - BACKGROUND: Phylogeography and historical demography of the cyprinid fish
Diptychus maculatus (subfamily Schizothoracinae) are evaluated across three river
systems in the Northern Qinghai-Tibetan Plateau (QTP) and Tien Shan range: the
Indus River, Tarim River and Ili River. RESULTS: Results from both mtDNA (16S
rRNA, Cyt b and D-loop) and nucDNA (RAG-2) resolved four reciprocally
monophyletic clades, representing populations from Indus River, South Tarim
River, North Tarim River and Ili River, respectively. The divergence times was
estimated to be 1.5-2.5 Mya. It is consistent with the hypothesis that the split
of four clades is the consequence of vicariance resulting from both the intensive
uplift of QTP and Tien Shan as well as the resultant expansion of the Taklimakan
Desert. Several lines of evidences indicate dynamic demographic histories for the
populations, with late Pleistocene and Holocene population bottlenecks and
expansions except the Indus River. CONCLUSIONS: Our results clearly depicted the
phylogenetic relationship of D. maculatus from Indus River, Tarim River and Ili
River. The analyses implicated the relationship among the distribution of D.
maculatus, paleo-drainages and geographic events, and implied the existence of
the South Tarim River in history.
PMID- 27613241
TI - Psychroflexus saliphilus sp. nov., isolated from a marine solar saltern.
AB - A Gram-stain-negative, non-motile, rod-shaped, orange-pigmented strain, WDS4A13T,
was isolated from a marine solar saltern in Weihai, China. Strain WDS4A13T grew
under optimal conditions of pH 7.0-8.0, 33 degrees C and with 6 % (w/v) NaCl.
Phylogenetic analysis based on 16S rRNA gene sequences showed that strain
WDS4A13T belonged to the genus Psychroflexus. The levels of similarity between
the 16S rRNA gene sequence of strain WDS4A13T and those of the type strains of
recognized species of the genus Psychroflexus were 92.0-97.3 %. The polar lipid
profile of the novel isolate consisted of two unidentified phospholipids,
diphosphatidylglycerol, phosphatidylethanolamine, a glycolipid and an
unidentified lipid as the major polar lipids. The predominant menaquinone was MK
6, and iso-C15 : 1 G, iso-C15 : 0 and C15 : 0 were the major fatty acids. The DNA
G+C content was 35.2 mol%. On the basis of phenotypic, chemotaxonomic and
phylogenetic data, strain WDS4A13T represents a novel species within the genus
Psychroflexus, for which the name Psychroflexus saliphilus sp. nov. is proposed.
The type strain is WDS4A13T (=MCCC 1H00134T=KCTC 52043T).
PMID- 27613242
TI - Fixed left ventricular outflow tract obstruction mimicking hypertrophic
obstructive cardiomyopathy: pitfalls in diagnosis.
AB - We present a case series that highlights the diagnostic challenges with left
ventricular hypertrophy (LVH) and left ventricular outflow tract obstruction
(LVOTO). Fixed structural lesions causing LVOTO with secondary LVH may mimic
hypertrophic obstructive cardiomyopathy (HOCM). Management of these two entities
is critically different. Misdiagnosis and failure to recognize fixed left
ventricular outflow tract (LVOT) lesions may result in morbidity as a result of
inappropriate therapy and delay of definitive surgical treatment. It is thus
necessary to identify the correct type and level of obstruction in the LVOT by
careful correlation of clinical examination, Doppler evaluation, and advanced
imaging findings.
PMID- 27613244
TI - Do the exome: A case of Williams-Beuren syndrome with severe epilepsy due to a
truncating de novo variant in GABRA1.
AB - Williams-Beuren syndrome (WBS) is a relatively common, clinically recognizable
microdeletion syndrome. In most cases the typical heterozygous deletion of 1.5 Mb
on chromosome 7q11.23 spanning about 26 genes can be identified. Also some larger
or smaller atypical deletions have been reported and associated with additional
or atypical phenotypic aspects. We report on an individual with typical WBS due
to the common deletion and with refractory infantile spasms. Using trio-exome
sequencing, we identified a de novo truncating variant c.1200del, p
(Lys401Serfs*25) in GABRA1 as the likely cause of the early onset epilepsy. This
unique case not only allows to further define the phenotypic spectrum of
infantile epileptic encephalopathy associated with rare de novo GABRA1 variants
but exemplifies the need for a sensitive review of unclear associations in
clinically defined syndromes and for extended diagnostic work-up in individuals
with unusual presentations of a genetically confirmed diagnosis.
PMID- 27613243
TI - Crucial genes associated with diabetic nephropathy explored by microarray
analysis.
AB - BACKGROUND: This study sought to investigate crucial genes correlated with
diabetic nephropathy (DN), and their potential functions, which might contribute
to a better understanding of DN pathogenesis. METHODS: The microarray dataset
GSE1009 was downloaded from Gene Expression Omnibus, including 3 diabetic
glomeruli samples and 3 healthy glomeruli samples. The differentially expressed
genes (DEGs) were identified by LIMMA package. Their potential functions were
then analyzed by the GO and KEGG pathway enrichment analyses using the DAVID
database. Furthermore, miRNAs and transcription factors (TFs) regulating DEGs
were predicted by the GeneCoDis tool, and miRNA-DEG-TF regulatory network was
visualized by Cytoscape. Additionally, the expression of DEGs was validated using
another microarray dataset GSE30528. RESULTS: Totally, 14 up-regulated DEGs and
430 down-regulated ones were identified. Some DEGs (e.g. MTSS1, CALD1 and ACTN4)
were markedly relative to cytoskeleton organization. Besides, some other ones
were correlated with arrhythmogenic right ventricular cardiomyopathy (e.g. ACTN4,
CTNNA1 and ITGB5), as well as complement and coagulation cascades (e.g. C1R and
C1S). Furthermore, a series of miRNAs and TFs modulating DEGs were identified.
The transcription factor LEF1 regulated the majority of DEGs, such as ITGB5,
CALD1 and C1S. Hsa-miR-33a modulated 28 genes, such as C1S. Additionally, 143
DEGs (one upregulated gene and 142 downregulated genes) were also differentially
expressed in another dataset GSE30528. CONCLUSIONS: The genes involved in
cytoskeleton organization, cardiomyopathy, as well as complement and coagulation
cascades may be closely implicated in the progression of DN, via the regulation
of miRNAs and TFs.
PMID- 27613245
TI - The effect of increased lipoproteins levels on the disposition of vincristine in
rat.
AB - BACKGROUND: Vincristine (VCR), an antineoplastic agent, is a key component in the
treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma,
neuroblastoma, and Wilms' tumor diseases. Recently, high incidence of
hyperlipidemia was reported to be associated with allogenic hematopoietic stem
cell transplantation and VCR/L-asparaginase therapy. The aim of this study is to
test the effects of incremental increase in lipoproteins levels on vincristine
disposition in rat. METHOD: To study VCR pharmacokinetics and protein binding,
rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate
(IHL) and extreme hyperlipidemic (HL). Hyperlipidemia was induced by ip injection
of (1 g/Kg) poloxamer 407 in rats. Serial blood samples were collected using the
pre-inserted jugular vein cannula for 72 h post VCR (0.15 mg/Kg) i.v. dose. VCR
unbound fractions in NL, IHL and HL plasma were determined using ultrafiltration
kits. RESULTS: VCR demonstrated a rapid distribution phase (6-8 h) followed by a
slower elimination phase with a mean elimination t1/2 of ~ 14 h. VCR exhibited
moderate binding to plasma proteins ~ 83 %. It showed a relatively small Vc
(~0.17 L/Kg) and a larger Vbeta (1.53 L/Kg) indicating good tissue distribution.
As the lipoproteins levels were increased, no significant changes were noted in
VCR unbound fraction, plasma concentration, or volume of distribution indicating
low affinity to lipoprotein binding. Induced HL also did not affect VCR
elimination where similar VCR AUC0-infinity, Cl and elimination phase t1/2 were
reported along the different lipemic groups. CONCLUSION: Incremental increase in
lipoprotein levels resulted in no significant effect on VCR disposition as such
ALL malignant lymphoma and allogenic hematopoietic stem cell transplantation
patients need not to worry about HL-VCR interaction. Whether, HL can potentiate
another drug-drug or drug-disease interaction involving VCR warrants further
studying and monitoring to ensure therapeutic safety and efficiency.
PMID- 27613246
TI - Developmental venous anomaly presenting as a spontaneous intraparenchymal
hematoma without thrombosis.
AB - INTRODUCTION: Developmental venous anomalies (DVAs) are cited as the most common
cerebral vascular malformations. Still, intracerebral hematomas are rarely
thought to be caused by DVAs. In this report, the authors present a unique case
of a DVA that hemorrhaged spontaneously, rather than hemorrhaging into a venous
infarction following DVA thrombosis as has been more commonly reported. CLINICAL
PRESENTATION: A 22-year-old previously healthy male presented to the emergency
department with a severe headache, confusion, and progressive hemiparesis. A
computed tomography (CT) scan demonstrated a spontaneous left parietal
intraparenchymal hemorrhage (IPH), with intraventricular extension and acute
hydrocephalus. CT angiography did not demonstrate an underlying vascular
malformation. The patient was taken emergently to the operating room for a left
parietal craniotomy for evacuation of the hematoma. Intraoperative pathology was
consistent with a DVA Postoperative magnetic resonance imaging (MRI), magnetic
resonance angiography (MRA), and magnetic resonance venography (MRV) did not
demonstrate a mass lesion, ischemic stroke, or underlying vascular malformation.
An MRI obtained three years previously for headaches was normal. A postoperative
diagnostic cerebral angiogram was normal. An MRI/MRA performed six months
postoperatively demonstrated two foci of abnormal vessels on susceptibility
weighted imaging (SWI), suggesting the presence of a venous vascular
malformation. A diagnostic cerebral angiogram obtained six months postoperatively
was again normal, including delayed imaging. CONCLUSION: Few reports have cited
DVA as the sole cause of intracerebral hemorrhage. While very rare, these reports
suggest hemorrhagic conversion of a venous infarction secondary to a thrombosed
DVA as a possible etiology, and several provide imaging consistent with this
diagnosis. This case study demonstrates a unique presentation of a hemorrhagic
DVA in the absence of thrombosis or stroke.
PMID- 27613247
TI - Identification and characterization of the novel point mutation m.3634A>G in the
mitochondrial MT-ND1 gene associated with LHON syndrome.
AB - Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease
characterized by bilateral acute or subacute progressive central visual loss.
Most cases of LHON syndrome are caused by point mutations in the MT-ND1, MT-ND4,
and MT-ND6 genes. Here, we report a novel homoplasmic mutation in the MT-ND1 gene
(m.3634A>G, p.Ser110Gly) in a patient with the classical clinical features of
LHON syndrome. Several observations support the idea that the mutation is
pathogenic and involved in the clinical phenotype of the patient: 1) The mutation
affected a highly conserved amino acid, 2) A pathogenic mutation in the same
amino acid (m.3635G>A, p.Ser110Asn) was previously reported in a patient with
LHON syndrome, 3) The mutation is not recorded in the Mitomap or Human
Mitochondrial Genome Database, 4) In silico predictors classified the mutation as
"probably damaging", and 5) Cybrids carrying the mutation showed decreased
Complex I enzyme activity, lower cell proliferation, and decreased mitochondrial
membrane potential relative to control cybrids.
PMID- 27613248
TI - Emergence of Brucella suis in dogs in New South Wales, Australia: clinical
findings and implications for zoonotic transmission.
AB - BACKGROUND: Animal reservoirs of brucellosis constitute an ongoing threat to
human health globally, with foodborne, occupational and recreational exposures
creating opportunities for transmission. In Australia and the United States,
hunting of feral pigs has been identified as the principal risk factor for human
brucellosis due to Brucella suis. Following increased reports of canine B. suis
infection, we undertook a review of case notification data and veterinary records
to address knowledge gaps about transmission, clinical presentation, and zoonotic
risks arising from infected dogs. RESULTS: Between 2011 and 2015, there was a 17
fold increase in the number of cases identified (74 in total) in New South Wales,
Australia. Spatial distribution of cases largely overlapped with high feral pig
densities in the north of the state. Ninety per cent of dogs had participated
directly in pig hunting; feeding of raw feral pig meat and cohabitation with
cases in the same household were other putative modes of transmission. Dogs with
confirmed brucellosis presented with reproductive tract signs (33 %), back pain
(13 %) or lameness (10 %); sub-clinical infection was also common (40 %).
Opportunities for dog-to-human transmission in household and occupational
environments were identified, highlighting potential public health risks
associated with canine B. suis infection. CONCLUSIONS: Brucellosis due to B. suis
is an emerging disease of dogs in Australia. Veterinarians should consider this
diagnosis in any dog that presents with reproductive tract signs, back pain or
lameness, particularly if the dog has a history of feral pig exposure. Moreover,
all people in close contact with these dogs such as hunters, household contacts
and veterinary personnel should take precautions to prevent zoonotic
transmission.
PMID- 27613249
TI - Laryngeal Cancer, HPV DNA vs E6/E7 mRNA Test: A Systematic Review.
AB - OBJECTIVE: The reported range of involvement of human papillomavirus (HPV) in
laryngeal squamous cell carcinoma (SCC) is wide because of the methods used to
detect HPV. DATA SOURCES: A computerized Medline study was carried out using the
following as key words: "Papillomavirus Infections"[Mesh] and "Laryngeal
Neoplasms"[Mesh]. MATERIALS AND METHODS: Studies that were included were written
in English and reported results of HPV DNA with RNA in laryngeal SCC. RESULTS:
There were six reported HPV mRNA extraction. Among these studies, Lewis et al
reported that out of the 31 cases analyzed, only 2 were HPV DNA+ and of these
only 1 was mRNA HPV+ (3%). Halec et al reported 102 cases of which 32 were HPV
DNA+ cases and of which only 6 were mRNA+ (5%). Chernock et al reported 76 cases
of which 13 were HPV DNA+ cases and of which 4 were mRNA+ (5%). Masand et al
reported 8 cases of which 1 was HPV DNA+ case and none was mRNA+. Gheit et al
reported 43 cases of which 4 were HPV DNA+ cases and of which 2 were mRNA+ (4%).
Castellsagne et al reported 1042 cases of which 59 were HPV DNA+ case and of
which 51 were mRNA+ (4.8%) CONCLUSIONS: When determining the role of HPV in
laryngeal SCC, evidence of HPV DNA warrants further examination for E6/E7 mRNA as
simple assays such as p16 are nonspecific in laryngeal SCC. Further studies of
HPV and its role in laryngeal SCC are warranted.
PMID- 27613251
TI - Pubertal age based on testicular and epididymal histology in Gottingen minipigs.
AB - Gottingen minipigs are used worldwide as nonrodent animal models for toxicologic
and pharmaceutical research. Having knowledge of the age for onset of puberty is
an important consideration when designing such biomedical experiments. The
present study reports an earlier age for puberty on the basis of changes in
testicular spermatogenic development in the Gottingen minipig. Testes and
epididymides of 24 Gottingen minipigs ranging 5 to 8 weeks of age were obtained
for histologic observation after hematoxylin-eosin staining. Microscopic
examination was performed to determine the prevalence of cell types (e.g.,
spermatogonia, primary and secondary spermatocytes, round spermatids, elongated
spermatids, luminal sperm) in seminiferous tubules and for the presence of sperm
in the cauda epididymis. Puberty was defined as having a majority cell type
presence of elongated spermatids in the seminiferous tubules in conjunction with
the presence of spermatozoa in the cauda epididymis. Puberty was identified in
two males at 6 weeks of age, two males at 7 weeks of age, and in all 6 males at 8
weeks of age. In conclusion, the age of puberty in male Gottingen minipigs occurs
by 8 weeks of age, an earlier age than previously reported.
PMID- 27613250
TI - Efficacy, safety, tolerability and pharmacokinetics of a novel human immune
globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary
immunodeficiencies.
AB - A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous
administration (IGSC 20%), would offer a new option for antibody replacement
therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy,
safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a
prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a
median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses
equivalent to those administered for previous intravenous or subcutaneous IgG
treatment. The rate of validated acute bacterial infections (VASBIs) was
significantly lower than 1 per year (0.022/patient-year, P < 0.0001); the rate of
all infections was 4.38/patient-year. Median trough IgG concentrations were >= 8
g/l. There was no serious adverse event (AE) deemed related to IGSC 20%
treatment; related non-serious AEs occurred at a rate of 0.101 event/infusion.
The incidence of local related AEs was 0.069 event/infusion (0.036
event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total
related local AEs). The incidence of related systemic AEs was 0.032
event/infusion. Most related AEs were mild, none were severe. For 64.6% of
patients and in 94.8% of IGSC 20% infusions, no local related AE occurred. The
median infusion duration was 0.95 (range = 0.3-4.1) h using mainly one to two
administration sites [median = 2 sites (range = 1-5)]. Almost all infusions
(99.8%) were administered without interruption/stopping or rate reduction. These
results demonstrate that IGSC 20% provides an effective and well-tolerated
therapy for patients previously on intravenous or subcutaneous treatment, without
the need for dose adjustment.
PMID- 27613252
TI - The effects of late gestation maternal nutrient restriction with or without
protein supplementation on endocrine regulation of newborn and postnatal beef
calves.
AB - A study was conducted to evaluate late gestation maternal nutrient restriction
(NR) with or without protein supplementation on endocrine regulation in newborn
beef calves. This study used multiparous cows (4 and 5 years of age, n = 57)
randomly assigned to one of three treatments for the last 100 days of gestation.
The control (Con; n = 19) cows were fed to increase body condition score, whereas
the NR (n = 19) and NR with protein supplement (NRS, n = 19) cows were fed to
lose 1.2 +/- 0.2 body condition score units during the last 100 days of
gestation. Control cows were allowed ad libitum access to tall fescue/crabgrass
paddock and, when grazing became insufficient, ad libitum hay was provided along
with 1.3 kg of corn gluten feed 5 days/wk. Tall fescue paddocks were strip grazed
to limit forage availability for NR and NRS. The NRS-treated dams were
individually penned and fed 0.45 kg of soybean meal 3 days/wk. As forage became
limited, the nutrient-restricted paddocks received limited fescue hay. After
parturition cow/calf pairs were moved to a common pasture and received ad libitum
silage and high-concentrate feed. Maternal NR regardless of supplementation
reduced cow plasma glucose and insulin concentrations during late gestation (P <
0.0001 and P = 0.0051, respectively). Calves from NR dams weighed less at birth
than Con calves (P = 0.04), whereas NRS calves were intermediate (33.4 +/- 1.2,
35.0 +/- 1.3, and 37.2 +/- 1.3 kg NR, NRS, and Con, respectively). Plasma glucose
concentrations of unsuckled calves at birth were reduced (P = 0.037) in NR and
NRS calves compared with Con (67.7 +/- 6.5 and 60.1 +/- 6.9 vs. 83.7 +/- 6.1
mg/dL, respectively). At birth, Con and NRS calves had increased (P = 0.0037)
plasma leptin concentrations compared with NR calves, whereas calf plasma
cortisol concentrations were greater for the nutrient-restricted groups than the
Con group (treatment * day P = 0.0135). Plasma IgG concentrations from calves at
5 days of age were similar (P = 0.701) between maternal late gestation
treatments. This research reports that late gestation NR reduces postnatal calf
birth weight, plasma glucose and leads to reduced plasma leptin. Maternal protein
supplementation appears to partially alleviate the effects of late gestation NR
on reducing plasma leptin, birth weight, and growth rate from Day 30 of age to
weaning.
PMID- 27613253
TI - Optimising non-invasive mechanical ventilation: Which unit should care for these
patients? A cohort study.
AB - BACKGROUND: Use of noninvasive ventilation (NIV) has extended beyond intensive
care units (ICUs), becoming usual practice in emergency departments (EDs) and
general wards. OBJECTIVE: To analyse the relationship between nursing care and
NIV outcome in different hospital units. DESIGN AND SETTINGS: Three university
hospitals and one community hospital participated in a prospective observational
cohort study. PARTICIPANTS: Ten units participated: 4 ICUs (1 surgical, 3 medical
surgical), 3 recovery (1 postsurgical, 2 EDs, 3 general wards). METHOD: Treatment
success/failure, interface intolerance and complications were evaluated according
to patient characteristics, nursing care provided, and procedures used.
Complications analysed included bronchoaspiration, pneumothorax, skin lesions,
inability to manage secretions, eye irritations, deteriorating level of
consciousness, gastric distension, and excessive air losses around the mask.
RESULTS: Of 387 patients, 194 (50.1%) were treated in ICU, 121 (31.3%) in ED, 38
(9.8%) postsurgery, and 34 (8.8%) in general wards. Regression analysis, adjusted
for APACHE score and NIV indication, showed 3.3 times greater risk of NIV failure
(95% CI [1.2-9.2]) in a university-hospital ICU with <50 NIV cases/year, compared
to a community hospital ICU. In ICUs and general wards, NIV was suspended in 12%
of patients due to interface intolerance. Acute-on-chronic lung diseases (ACLD)
had lower risk of NIV failure (OR 0.2 [95% CI 0.06-0.69]) and lack of
humidification was not associated with treatment failure (OR 0.2 [95% CI 0.1
0.4]). Poor secretion management was linked to pneumonia (OR 2.5 [95% CI 1.1
5.9]) and early weaning/extubation (OR 3.3 [95% CI 1.2-8.9]). Interface
intolerance was associated with conventional ICU ventilators (OR 4.4 [95% CI 2.1
9.2]) and nasal skin lesions with excessive air losses (OR 2.4 [95% CI 1.1-5.3]),
especially with oronasal masks (OR 3.5 [95% CI 1.1-11.3]). CONCLUSIONS: Acute
respiratory failure patients with pneumonia admitted to general wards had
increased interface intolerance and NIV failure. Rotating mask types could
improve NIV success in any unit administering this therapy.
PMID- 27613254
TI - Hydrophilic-hydrophobic polymer blend for modulation of crystalline changes and
molecular interactions in solid dispersion.
AB - This research study aimed to develop a new strategy for using a polymer blend in
solid dispersion (SD) for dissolution enhancement of poorly water-soluble drugs.
SDs with different blends of hydrophilic-hydrophobic polymers (zein/hydroxypropyl
methylcellulose - zein/HPMC) were prepared using spray drying to modulate the
drug crystal and polymer-drug interactions in SDs. Physicochemical
characterizations, including power X-ray diffraction and Fourier transform
infrared spectroscopy, were performed to elucidate the roles of the blends in
SDs. Although hydrophobic polymers played a key role in changing the model drug
from a crystal to an amorphous state, the dissolution rate was limited due to the
wetting property. Fortunately, the hydrophilic-hydrophobic blend not only reduced
the drug crystallinity but also resulted in a hydrogen bonding interaction
between the drugs and the polymer for a dissolution rate improvement. This work
may contribute to a new generation of solid dispersion using a blend of
hydrophilic-hydrophobic polymers for an effective dissolution enhancement of
poorly water-soluble drugs.
PMID- 27613255
TI - Gemcitabine-based polymer-drug conjugate for enhanced anticancer effect in colon
cancer.
AB - In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic
biodegradable polymeric drug carriers. Our aim was to increase the
chemotherapeutic potential of GEM in colon cancer by forming a unique polymer
drug conjugates. The polymer-drug conjugate micelles were nanosized with a
typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)
poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH
conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a
typical time dependent manner. The clonogenic assay further confirmed the
superior anticancer effect of GEM-PL which showed least number of colonies. GEM
PL formulation exhibited a significantly higher apoptosis of cancer cells (~25%)
when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA
significantly enhanced the blood circulation potential in animal model compared
to that of free GEM. GEM-PL could prevent quick elimination of the drug and can
provide sufficient time for the greater accumulation of GEM at the tumor sites.
GEM-PL showed a remarkable tumor regression effect as evident from the lowest
tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates
showed the potential of polymer-based drug targeting and might hold significant
clinical potential in the treatment of colon cancers.
PMID- 27613256
TI - Low density lipoprotein receptor targeted doxorubicin/DNA-Gold Nanorods as a
chemo- and thermo-dual therapy for prostate cancer.
AB - As drug vehicles and therapeutics, Gold Nanorods (GNRs) have various merits such
as easy preparation and modification, passive accumulation to tumor tissues,
effective intracellular delivery of therapeutics, and thermal responses to laser
radiation. Doxorubicin (DOX) has been the standard chemotherapy for cancer. To
enhance the anti-cancer efficacy, chemotherapy and thermotherapy were combined in
the present study. To load sufficient DOX, DOX was first intercalated into DNA
double strands and then absorbed to GNRs. PEG (polyethylene glycol) was used to
modify DOX/DNA-GNRs to prolong circulation in vivo and to enhance its stability.
Low density lipoprotein receptor (LDLR) targeted peptide-RLT (R) was also bound
to DOX/DNA-GNRs to increase their specificity to LDLR over-expressed cancer
cells. DNA-GNRs-PEG/R was successfully prepared with high in vitro stability in
this study and DOX was loaded sufficiently to obtain DOX/DNA-GNRs-PEG/R. DOX/DNA
GNRs-PEG/R with near infrared (NIR) laser treatment showed higher inhibition to
MCF-7 cells and PC-3 cells and both DOX/DNA-GNRs-PEG/R with/without NIR laser
treatment were more potent than free DOX. Cell uptake experiment indicated that
DOX loaded in DNA-GNRs-PEG/R was taken by PC-3 cells much faster than free DOX.
With DOX/DNA-GNRs-PEG/R, the apoptosis rate and necrosis rate of PC-3 cells
increased 1.7 and 6.4 folds respectively compared to free DOX. Additional NIR
laser treatment caused significantly increases in PC-3 cell necrosis. DOX/DNA
GNRs-PEG/R+laser also enhanced the inhibition of S phase of PC-3 cells by DOX.
ROS (reactive oxygen species) assay showed that DOX/DNA-GNRs-PEG/R produced much
more ROS than free DOX. With additional laser treatment, further increase in ROS
was detected. Prostate cancer model was achieved by injecting PC-3 cells into
nude mice and the results showed that more DNA-GNRs-PEG/R was observed in tumor
cells and higher tumor inhibition rate was achieved in vivo with R modification.
Conclusively, all results consistently indicated that DNA-GNRs-PEG/R was able to
increase in vitro and in vivo anti-cancer efficacy of DOX. With additional NIR
laser treatment, GNRs produced heat and further enhanced the anti-cancer effect
achieved by DOX/DNA-GNRs-PEG/R. Therefore, the chemo- and thermo-dual therapy
could be a potential combined therapy for more efficient anti-cancer treatment in
clinical applications.
PMID- 27613258
TI - Ulcer of the Duodenum Caused by a Pancreatic Neuroendocrine Tumor in an
Adolescent.
PMID- 27613259
TI - Choledochocolonic Fistula as the Cause for Chronic Diarrhea.
PMID- 27613257
TI - Low Rate of Dysplasia Detection in Mucosa Surrounding Dysplastic Lesions in
Patients Undergoing Surveillance for Inflammatory Bowel Diseases.
AB - BACKGROUND & AIMS: When dysplastic lesions are encountered during surveillance
colonoscopy of patients with inflammatory bowel disease (IBD), guidelines
recommend collection of additional biopsies from the surrounding mucosa to ensure
the lesion has been adequately circumscribed. We aimed to determine the rate of
dysplasia in mucosa biopsies collected from tissues surrounding dysplastic
lesions during IBD surveillance. METHODS: In a retrospective study, we collected
endoscopy and pathology reports from 1065 patients undergoing colonoscopic
surveillance for IBD from 2000 through 2015 at 3 centers in the Netherlands. We
analyzed reports from all patients with dysplastic lesions from whom biopsies of
surrounding mucosa were collected. Among 194 patients with 1 or more visible
dysplastic lesions, mucosal biopsies were collected from tissues adjacent to 140
dysplastic lesions from 71 patients (63% male; 48% with ulcerative colitis, 42%
with Crohn's disease, and 10% with indeterminate colitis). RESULTS: The mean
number of surrounding mucosa biopsies collected per lesion was 3.4 (range, 1-6).
Dysplasia was detected in 7 biopsies surrounding 140 areas of dysplasia (5.0%)
and 5 biopsies surrounding 136 areas of low-grade dysplasia (3.7%). Dysplasia in
biopsies of surrounding mucosa could be observed during 5 of 87 white light
endoscopies and during 2 of 53 chromoendoscopies. In patients with dysplasia in
mucosa surrounding lesions of low-grade dysplasia, post-resection surveillance
did not reveal high-grade dysplasia or colorectal cancer. CONCLUSIONS: Dysplasia
is detected in only 5% of biopsies collected from mucosa surrounding dysplastic
lesions. This observation indicates that endoscopists accurately delineate the
borders of dysplastic lesions during surveillance of patients with IBD. The lack
of clinical consequences from routinely collecting biopsies from areas
surrounding dysplastic lesions casts doubt on the usefulness and cost
effectiveness of this practice.
PMID- 27613260
TI - Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk
Factors, and Effects on Quality of Life.
AB - BACKGROUND & AIMS: Systemic scleroderma (SSc) is associated with esophageal
aperistalsis and hypotensive esophagogastric junction pressure, although there
could be a gradation in esophageal motor dysfunction. We characterized esophageal
motor function by high-resolution esophageal manometry (HRM) and assessed
associations between SSc severity, health-related quality of life (HRQOL), and
HRM findings in patients. METHODS: We performed a prospective study of 200
patients with SSc and 102 patients without SSc (controls) who underwent HRM at
Mayo Clinic Arizona from May 2006 through January 2015. We used data on
integrated relaxation pressure, distal contractile integral, and distal latency
to classify esophageal motility disorders according to the Chicago Classification
v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal
symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were
compared among diffuse SSc, limited SSc, and control subjects. Categorical
variables were compared by using the chi2 or Fisher exact test; continuous
variables were compared by using Mann-Whitney or Kruskal-Wallis test.
Multivariable logistic regression was used to assess the association between
severity of esophageal dysmotility and baseline clinical factors. RESULTS: Among
patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%).
Absent contractility was more frequent in patients with SSc than in controls (56%
vs 13%; P < .001). HRM findings varied among the patients; absent contractility
(56%) was the most frequent diagnosis, followed by normal motility (26%) and
ineffective esophageal motility (10%). Classic scleroderma esophagus
(esophagogastric junction pressure with absent contractility) was only observed
in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe
esophageal dysmotility was associated with disease duration, interstitial lung
disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was
decreased in patients with SSc and severe esophageal dysmotility. CONCLUSIONS:
Although severe dysmotility is more common in patients with SSc than in controls,
we observed the so-called scleroderma esophagus in only one-third of patients
with SSc. Esophageal motor function appears to be heterogeneous in SSc.
Esophageal dysmotility reduces HRQOL in patients with SSc.
PMID- 27613261
TI - Incomplete Colonic Obstruction Caused by Extramedullary Plasmacytoma.
PMID- 27613262
TI - 'Myxoedema madness' with Capgras syndrome and catatonic features responsive to
combination olanzapine and levothyroxine.
AB - We present the case of an elderly woman with hypothyroidism and no psychiatric
history who presented with new onset of psychosis, paranoia, catatonic features
and Capgras syndrome (CS). This case illustrates the spectrum of neuropsychiatric
symptoms that may accompany hypothyroidism and the importance of considering
thyroid dysfunction as a primary contributor to severe psychiatric symptoms,
especially in previously stable patients. We demonstrate the effectiveness of
combination levothyroxine and olanzapine, with its favourable cardiac profile, in
the treatment of myxoedema madness. Antipsychotics can be weaned once psychiatric
symptoms resolve and hormone levels are stabilised.
PMID- 27613264
TI - Granulomatous hypophysitis: a case of severe headache.
AB - Idiopathic granulomatous hypophysitis (GH) is an uncommon inflammatory disease of
the pituitary with impairment of pituitary gland function due to infiltration by
lymphocytes, plasma cells and macrophages. We report the case of a 39-year-old
woman who presented with worsening of headaches for 1 month and blurring of
vision over 5 days. An MRI revealed a homogeneous supra-sellar mass evoking a
pituitary tumour with bulky pituitary stalk extending into the left and right
cavernous sinuses. Hormonal investigations showed anterior pituitary hormone
deficiencies; meanwhile histopathological examination revealed an aspect of
hypophysitis. Clinical and radiological remission occurred immediately
postglucocorticoid therapy with the addition of a steroid-sparing agent later in
view of recurrence of symptoms on glucocorticoid dose reduction. GH has important
diagnostic and therapeutic implications, as clinical and radiological features
ameliorate via medical treatment. With further understanding and recognition of
the disease, we hope to highlight a case of GH, in which signs and symptoms
improved after initiation of corticosteroids.
PMID- 27613265
TI - Unilateral testicular microlithiasis: a rare paediatric incidental finding.
PMID- 27613263
TI - Eosinophilic gastroenteritis: a challenge to diagnose and treat.
AB - The patient presented with bloody diarrhoea, and crampy abdominal pains. She was
diagnosed with eosinophilic gastroenteritis (EGE) after the finding of
persistently high peripheral eosinophil counts and histology of endoscopic
biopsies. She responded to steroids but became dependent on it and her symptoms
recurred on steroid tapering. There was little improvement with alternative
treatment such as budesonides, azathioprine and montelukast. Surprisingly her
symptoms improved significantly after she was treated with clarithromycin for
chest infection and she was continued on clarithromycin. Her eosinophil counts
fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the
mucosal thickening had improved. She became completely free of the symptoms since
she was on clarithromycin and her eosinophils counts fell within the normal range
during the follow-up.
PMID- 27613266
TI - Scedosporium apiospermum: a rare cause of malignant otitis externa.
AB - A 79-year-old man, with a history of well-controlled diabetes mellitus, presented
with left-sided otalgia. With an initial diagnosis of simple otitis externa, he
was discharged on topical drops. He represented 2 months later with worsening
otalgia and discharge. A diagnosis of malignant otitis externa was made based on
clinical and radiological findings. Intravenous Tazocin and Gentamicin were given
based on previous bacterial culture from ear swabs. The patient failed to improve
and developed left-sided facial nerve palsy. His condition stabilised following a
change in antimicrobial therapy and his management continued in the community on
intravenous Meropenem with twice weekly aural toilet. Repeated nuclear medicine
imaging failed to demonstrate resolution. A bony sequestration was removed from
the external auditory canal in the outpatient clinic, which following extended
culture grew Scedosporium apiospermum; his management was subsequently changed to
oral Voriconazole. This led to rapid clinical improvement and disease resolution
over a 6 -week period.
PMID- 27613267
TI - Hypoglycaemic injury spares thalamus, spoils striatum and leaves only a rest
tremor.
PMID- 27613268
TI - Digital ischaemia secondary to steal syndrome from a brachiocephalic
arteriovenous fistula.
PMID- 27613269
TI - Influence of perineural invasion in predicting overall survival and disease-free
survival in patients With locally advanced gastric cancer.
AB - BACKGROUND: The aim of the present study was to evaluate the prognostic
significance of perineural invasion (PNI) in locally advanced gastric cancer
patients who underwent D2 gastrectomy and adjuvant chemotherapy. METHODS: The
records of a series of 103 patients undergoing D2 gastrectomy with curative
intent combined with adjuvant chemotherapy from January 2004 to December 2014
were retrospectively reviewed. RESULTS: PNI was positive in 47 (45.6%) specimens.
The 1-, 3-, and 5-year overall survival rates were 81%, 55%, and 42%,
respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 76%,
57%, and 49%, respectively. A multivariate analysis showed that age number of
positive lymph nodes, T stage, and PNI were independently associated with overall
survival. Regarding DFS, the multivariate analysis showed that only PNI was
independently associated with DFS. CONCLUSIONS: PNI and T stage and positive
lymph nodes are independent markers of poor prognosis in patients with gastric
cancer. PNI should be incorporated in the postoperative staging system for
planning follow-up after surgery and in our opinion to propose more aggressive
postoperative therapies in PNI-positive patients.
PMID- 27613270
TI - Antineoplastic potential of metformin in colorectal cancer.
PMID- 27613272
TI - Nutrients, phytochemicals and antioxidant activities of 26 kidney bean cultivars.
AB - Detailed characterization in nutrients and phytochemicals with antioxidant
activities of 26 kidney beans was performed. The kidney beans contained high
levels of dietary fiber (29.32-46.77%), resistant starch (9.16-18.09%) and
protein (22.06-32.63%) but low levels of lipid (1.05-2.83%) and sugars (1.55
9.07%). The monosaccharide composition of soluble fiber was dominated by
arabinose, galactose, mannose and galacturonic acid. The ratio of essential amino
acid to the total amino acid was ranged from 0.29 to 0.36. The predominant fatty
acid was polyunsaturated fatty acids, accounting for 47.54-67.26% of total fatty
acids. The total tocopherol content was in the range of 12.83-68.35 MUg/g,
predominantly gamma-tocopherol, followed by delta-tocopherol. In addition,
certain levels of total phenolics and flavonoids with respective values of 0.25
3.79 mg gallic acid equivalent/g dry weight and 0.19-7.05 mg rutin equivalent/g
dry weight resulted in significant antioxidant activities. And a good correlation
was observed between TPC and FRAP values (R2 = 0.8030). The results indicated
that kidney beans are excellent sources of health-promoting compounds.
PMID- 27613273
TI - Cytomegalovirus as a cause of hypertensive anterior uveitis in immunocompetent
patients.
AB - BACKGROUND: The aims of this study are to investigate the clinical
characteristics of patients with anterior hypertensive uveitis and to compare the
characteristics between patients in cytomegalovirus (CMV)-positive and CMV
negative groups in their aqueous humor samples. Immunocompetent patients (n = 42)
with a history of chronic and/or recurrent hypertensive anterior uveitis
underwent ophthalmic examination and serological tests. Among the 42 patients
with hypertensive anterior uveitis, aqueous humor sampling was performed in 21,
and they were analyzed for viral deoxyribonucleic acids using the polymerase
chain reaction (PCR). RESULTS: The average age of the 42 patients with
hypertensive anterior uveitis was 57.6 years, and 29 (69.0 %) of the subjects
were males. Of the patients, 22 (52.4 %) underwent glaucoma surgery, and the
average corneal endothelial cell counts were 1908 cells/mm(2). Among the 21
patients who underwent an aqueous sampling, 6 were positive for CMV-DNA, while 15
were negative. The frequency of glaucoma surgery was similar between groups (CMV
positive vs. CMV negative, 66.0 vs. 66.0 %, P = 0.701). However, 66.7 % of the
CMV-positive group underwent glaucoma tube shunt surgery, whereas 80 % of the CMV
negative group underwent trabeculectomy or received an ExPRESS glaucoma
filtration device (Alcon, Fort Worth, TX) for glaucoma surgery (P = 0.095). The
corneal endothelial cell counts were significantly lower in the CMV-positive
group (CMV positive vs. CMV negative, 1245 +/- 560 vs. 1981 +/- 387 cells/mm(2);
P = 0.009). CONCLUSIONS: CMV was found to be an etiological factor in patients
with hypertensive anterior uveitis in Korea. Special caution is needed for
patients with CMV-induced hypertensive anterior uveitis, considering its adverse
effect on the corneal endothelium.
PMID- 27613274
TI - Morphological assessment of the retina in uveitis.
AB - BACKGROUND: The objective of this study is to describe a system for color
photograph evaluation in uveitis and report baseline morphologic findings for the
Multicenter Uveitis Steroid Treatment (MUST) Trial. Four-hundred seventy-nine
eyes of 255 subjects with intermediate, posterior, and panuveitis had
stereoscopic color fundus photographs obtained by certified photographers and
evaluated by certified graders using standardized procedures to evaluate
morphologic characteristics of uveitis. The posterior pole was evaluated for
macular edema, vitreoretinal interface abnormalities, and macular pigment
disturbance/atrophy; the optic disk was assessed for edema, pallor, or
glaucomatous changes. The presence of neovascularization, vascular occlusion,
vascular sheathing, and tractional retinal changes was determined. A random
subset of 77 images was re-graded to determine the percentage agreement with the
original grading on a categorical scale. RESULTS: At baseline, 437/479 eyes had
images available to grade. Fifty-three eyes were completely ungradable due to
media opacity. Common features of intermediate and posterior/panuveitis were
epiretinal membrane (134 eyes, 35 %), and chorioretinal lesions (140 eyes, 36 %).
Macular edema was seen in 16 %. Optic nerve head and vascular abnormalities were
rare. Reproducibility evaluation found exact agreement for the presence of
chorioretinal lesions was 78 %, the presence and location of macular edema was 71
%, and the presence of epiretinal membrane was 71 %. Vertical cup-to-disk ratio
measurement had intra-class correlation of 0.75. CONCLUSIONS: The MUST system for
evaluating stereoscopic color fundus photographs describes the morphology of
uveitis and its sequelae, in a standardized manner, is highly reproducible, and
allows monitoring of treatment effect and safety evaluation regarding these
outcomes in clinical trials.
PMID- 27613271
TI - The clinical impact of artemisinin resistance in Southeast Asia and the potential
for future spread.
AB - Artemisinins are the most rapidly acting of currently available antimalarial
drugs. Artesunate has become the treatment of choice for severe malaria, and
artemisinin-based combination therapies (ACTs) are the foundation of modern
falciparum malaria treatment globally. Their safety and tolerability profile is
excellent. Unfortunately, Plasmodium falciparum infections with mutations in the
'K13' gene, with reduced ring-stage susceptibility to artemisinins, and slow
parasite clearance in patients treated with ACTs, are now widespread in Southeast
Asia. We review clinical efficacy data from the region (2000-2015) that provides
strong evidence that the loss of first-line ACTs in western Cambodia, first
artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to
K13 mutated parasites. The ring-stage activity of artemisinins is therefore
critical for the sustained efficacy of ACTs; once it is lost, rapid selection of
partner drug resistance and ACT failure are inevitable consequences. Consensus
methods for monitoring artemisinin resistance are now available. Despite
increased investment in regional control activities, ACTs are failing across an
expanding area of the Greater Mekong subregion. Although multiple K13 mutations
have arisen independently, successful multidrug-resistant parasite genotypes are
taking over and threaten to spread to India and Africa. Stronger containment
efforts and new approaches to sustaining long-term efficacy of antimalarial
regimens are needed to prevent a global malaria emergency.
PMID- 27613275
TI - Copper(II), cobalt(II) and nickel(II) complexes of juglone: synthesis, structure,
DNA interaction and enhanced cytotoxicity.
AB - Three novel copper(II), cobalt(II), and nickel(II) complexes of juglone (Jug)
containing 1,10-phenanthroline (phen) ligand, [M(Jug)2(phen)] (M = Cu(II), 1,
Co(II), 2, and Ni(II), 3), have been synthesized and characterized using,
elemental analysis and spectroscopic studies. Their interactions with calf thymus
DNA were investigated using viscosity measurements, UV-visible and fluorescence
spectrophotometric methods. The catalytic activities on DNA cleavage of the
complexes 1-3 were studied, which copper complex 1 showed better catalyst
activity in the DNA cleavage process than complexes 2 and 3. The in vitro
cytotoxic potential of the complexes 1-3 against human cervical carcinoma (HeLa),
human liver hepatocellular carcinoma (HepG-2), and human colorectal
adenocarcinoma (HT-29) cells indicated their promising antitumor activity with
quite low IC50 values in the range of 0.09-1.89 MUM, which are 75 times lower
than those of cisplatin.
PMID- 27613276
TI - Is treatment for bipolar disorder more effective earlier in illness course? A
comprehensive literature review.
AB - BACKGROUND: We aimed to investigate a key element of the early intervention
approach whether treatment at an earlier stage of bipolar disorder is more
effective than later in its course. METHODS: A comprehensive literature review
using Medline, Embase, Psychinfo, PsycArticle, and Web of Science, as data
sources, with a subsequent narrative synthesis. Study quality was assessed using
the Cochrane risk of bias method. RESULTS: Our search strategy yielded eight
primary papers and two meta-analyses (of psychological therapies and Olanzapine)
in total representing 8942 patients. Five studies focused on comparisons between
first and multiple episodes, and the others on fewer vs more episode categories.
There was a consistent finding, suggesting treatment in earlier illness stage
resulted in better outcomes in terms of response, relapse rate, time to
recurrence, symptomatic recovery, remission, psychosocial functioning, and
employment. This effect was found for pharmacological (Lithium, Olanzapine,
Divalproex) and psychological treatments. LIMITATIONS: There was high risk of
selection, performance, and attrition bias in most studies. First admission or
presentation is unlikely to equate to first episode, because of the duration of
untreated illness. Some patients having experienced multiple episodes could be
"treatment resistant". Study heterogeneity precluded meta-analysis. CONCLUSIONS:
Psychological and pharmacological treatments in the early stages of illness are
more effective than in the later stages of bipolar disorder across multiple
domains. There is a first episode and the early phase effect. Consistent with the
staging model of illness, findings provide evidence for the clinical utility of
an early intervention approach in bipolar disorder to improve patient outcomes.
PMID- 27613277
TI - Acute demyelination following radiotherapy for glioma: a cautionary tale.
AB - Radiotherapy is the mainstay of treatment after surgery for high-grade gliomas
and is usually well tolerated. Radiation toxicity in the brain is usually
classified according to the timing of side effects in relation to treatment, as
either acute (during radiotherapy), early delayed (within 12 weeks of
radiotherapy) or late delayed (months to years after radiotherapy). We report two
cases of young women who developed severe acute demyelination within 4 months of
radiotherapy for glioma, one of whom had a previous history of transverse
myelitis. Both improved with corticosteroids and remain in tumour remission.
These cases emphasise the importance of careful discussion with patients before
starting radiotherapy if there is a previous history of central nervous system
demyelination or multiple white matter lesions on MRI.
PMID- 27613279
TI - Making good choices: toward a theory of well-being in medicine.
AB - The principle of beneficence directs healthcare practitioners to promote
patients' well-being, ensuring that the patients' best interests guide treatment
decisions. Because there are a number of distinct theories of well-being that
could lead to different conclusions about the patient's good, a careful
consideration of which account is best suited for use in the medical context is
needed. While there has been some discussion of the differences between
subjective and objective theories of well-being within the bioethics literature,
less attention has been given to the questions of what work a theory of well
being needs to do in bioethics and which standards of success ought to be used in
selecting a theory of well-being for use in medicine. In this article, I argue
that traditional theories of well-being developed in philosophy are not well
suited to meet the needs of the medical context. For the principle of beneficence
to be most useful, the underlying account of well-being should satisfy two
conditions: first, it needs to lead to a concrete, action-guiding determination
of the patient's good; and, second, any recommendations it offers need to be
justifiable to patients. Standard accounts of well-being have difficulty
satisfying both conditions. Exploring the limitations of these theories when
applied to treatment dilemmas helps point the way toward the development of an
account of well-being better suited to healthcare.
PMID- 27613282
TI - Ratio of mBDNF to proBDNF for Differential Diagnosis of Major Depressive Disorder
and Bipolar Depression.
AB - There is a high rate of misdiagnosis between major depressive disorder (MDD) and
bipolar disorder (BD) in clinical practice. Our previous work provided suggestive
evidence for brain-derived neurotrophic factor (BDNF) in differentiating BD from
MDD. In this study, we aimed to investigate the role of mature BDNF (mBDNF) and
its precursor (proBDNF) in distinguishing bipolar depression (BP) from MDD during
acute depressive episode. A total of 105 participants, including 44 healthy
controls, 37 MDD patients and 24 BP patients, were recruited. Enzyme-linked
immunosorbent assay kits were applied to measure plasma mBDNF levels and proBDNF
levels of all participants. Plasma mBDNF levels were significantly decreased in
BP group than those in MDD group (P = 0.001) and healthy controls (P = 0.002).
Significantly higher ratio of mBDNF to proBDNF (M/P) at baseline was showed in
MDD group than those in BP group as well as in healthy controls (P = 0.000 and P
= 0.000, respectively). The optimal model for discriminating BP was the M/P ratio
(area under the ROC curve = 0.858, 95 % CI 0.753-0.963). Furthermore, the M/P
ratio was restored to normal levels after antidepressants treatment in MDD group.
In summary, our data demonstrated that both plasma mBDNF levels and M/P ratio
were lower in BP compared with MDD. These findings further support M/P ratio as a
potential differential diagnostic biomarker for BP among patients in depressive
episodes.
PMID- 27613283
TI - Sigmoid Sinus Characteristics Correlate with Early Clinical and Imaging
Surrogates in Anterior Circulation Ischemic Stroke.
AB - Cerebral venous outflow may play a decisive role in acute ischemic stroke. Here,
we assessed the relation of cerebral sinus vein characteristics with clinical and
imaging surrogates of early outcome in acute ischemic stroke. We evaluated
cerebral vein characteristics in 212 patients with the middle cerebral artery
(MCA) occlusive stroke confirmed by CT angiography CTA within 6 h from symptom
onset. Readout parameters included volume and density of the sigmoid sinus (SS)
and density of the superior sagittal sinus (SupSagS). These were correlated with
early clinical outcome defined as hospital death (HD), final infarct volume
(FIV), and National Institute of Health Stroke Scale (NIHSS) at discharge. We
found a correlation for the volume of the right SS and the FIV when the M1
segment of the MCA of either side was occluded (p = 0.002, Rho = 0.206, n = 134).
A decrease in SS density was more pronounced in the subgroup with unfavorable
outcome (NIHSS > 15 + HD) but only when the left hemisphere was affected (p =
0.026, n = 101). On stepwise logistic regression analysis, adjusted for on
admission NIHSS, age at presentation, and FIV, smaller SS volume was
independently associated with lower odds for hospital death (n = 183, OR 0.13, 95
% CI 0.02-0.94, p = 0.043). A larger right SS and a decrease in density increase
the risk of unfavorable early clinical and imaging outcome in AIS. This finding
of an outflow pattern independent of the stroke site implicates an involvement of
the cerebral venous drainage system in the pathophysiology of ischemic stroke.
PMID- 27613281
TI - Current Understanding of Platelet-Activating Factor Signaling in Central Nervous
System Diseases.
AB - Platelet-activating factor (PAF) is a bioactive lipid mediator which serves as a
reciprocal messenger between the immune and nervous systems. PAF, a pluripotent
inflammatory mediator, is extensively expressed in many cells and tissues and has
either beneficial or detrimental effects on the progress of inflammation-related
neuropathology. Its wide distribution and various biological functions initiate a
cascade of physiological or pathophysiological responses during development or
diseases. Current evidence indicates that excess PAF accumulation in CNS diseases
exacerbates the inflammatory response and pathological consequences, while
application of PAF inhibitors or PAFR antagonists by blocking this signaling
pathway significantly reduces inflammation, protects cells, and improves the
recovery of neural functions. In this review, we integrate the current findings
of PAF signaling in CNS diseases and elucidate topics less appreciated but
important on the role of PAF signaling in neurological diseases. We propose that
the precise use of PAF inhibitors or PAFR antagonists that target the specific
neural cells during the appropriate temporal window may constitute a potential
therapy for CNS diseases.
PMID- 27613285
TI - Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a
Scoping Review of Serious or Hospitalized Infections in Observational Studies.
AB - Biologic use is a major advance in the treatment of several autoimmune
conditions, including rheumatoid arthritis. In this review, we summarize key
studies of serious/hospitalized infections in rheumatoid arthritis (RA). RA is a
risk factor for infections. High RA disease activity is associated with higher
risk of serious infection. The risk of serious infections with tumor necrosis
factor inhibitor (TNFi) biologics is increased in the first 6 months of
initiating therapy, and this risk was higher compared to the use of traditional
disease-modifying anti-rheumatic drugs (DMARDs). Emerging data also suggest that
biologics may differ from each other regarding the risk of serious or
hospitalized infections. Past history of serious infections, glucocorticoid dose,
and older age were other important predictors of risk of serious infections in
patients treated with biologics.
PMID- 27613284
TI - Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and
Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex.
AB - Ciguatera fish poisoning (CFP) is a common human food poisoning caused by
consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people
worldwide each year. CTXs are classified depending on their origin from the
Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the
most toxic CTX known and the major source of CFP causing an array of neurological
symptoms. Neurological symptoms in some CFP patients last for several months or
years; however, the underlying electrophysiological properties of acute exposure
to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in
the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG)
activity was reduced remarkably in 2 h and returned to normal in 6 h after a
single exposure. However, second exposure to P-CTX-1 induced not only a further
reduction in EEG activities but also a 2-week delay in returning to baseline EEG
values. Ciguatoxicity was detected in the brain hours after the first and second
exposure by mouse neuroblastoma assay. The spontaneous firing rate of single
motor cortex neuron was reduced significantly measured by single-unit recording
with high spatial resolution. Expression profile study of neurotransmitters using
targeted profiling approach based on liquid chromatography-tandem mass
spectrometry revealed an imbalance between excitatory and inhibitory
neurotransmitters in the motor cortex. Our study provides a possible link between
the brain oscillations and neurotransmitter release after acute exposure to P-CTX
1. Identification of EEG signatures and major metabolic pathways affected by P
CTX-1 provides new insight into potential biomarker development and therapeutic
interventions.
PMID- 27613287
TI - Genomic characterization of three bovine viral diarrhea virus isolates from
cattle.
AB - Three strains of the bovine viral diarrhea virus (BVDV) were isolated from cattle
in Beijing, China. To investigate their genomic features, we sequenced and
characterized the complete genome of each of the isolates. Each of the three
virus genomes is about 12,220 bp in length, containing a 5' untranslated region
(UTR), one open reading frame (ORF) encoding a 3897-amino-acid polypeptide, and a
3' UTR. The nucleotide sequence of the three isolates were 99.0 % identical to
each and other shared nucleotide sequence identities of 73.4 % to 98.3 % with
other BVDV-1 strains, about 70.0 % with BVDV-2 strains, about 67.0 % with BVDV-3,
and less than 67.0 % with other pestiviruses. Phylogenetic analysis of the full
length genome, 3' UTR, and the Npro gene demonstrated that the three viruses were
BVDV-1 isolates. This is the first report of complete genome sequences of BVDV 1d
isolates from China and might have implications for vaccine development.
PMID- 27613286
TI - Low prevalence of hepatitis B vaccine escape mutants among individuals born after
the initiation of a nationwide vaccination program in Iran.
AB - A nationwide hepatitis B virus (HBV) vaccination program for neonates was
launched in Iran in 1993. Despite the success of this program, concern about its
long-term success still remains, because breakthrough infections due to emergence
of surface mutants have been reported in immunized children. We aimed to evaluate
the seroprevalence of HBV and vaccine escape mutants among individuals born after
the initiation of the nationwide vaccination program in Iran. This study included
1115 participants younger than 23 years old, with 223 in each age cohort. The
presence of HBsAg, anti-HBs and anti-HBc was evaluated using an ELISA kit. HBV
DNA levels were measured in anti-HBc and/or HBsAg-positive subjects. PCR products
were sequenced and mutations were identified. The overall HBsAg prevalence was
0.27 %. Anti-HBs and anti-HBc positive rates were 48 % and 0.18 %, respectively.
Two individuals were positive for anti-HBc, one of whom was also positive for
HBsAg, and the other was positive for anti-HBc only. HBV DNA was detected in
three out of four anti-HBc-and /or HBsAg-positive subjects. An I195M mutation
within the S gene was detected in two of the three HBV-DNA-positive cases. A very
low prevalence of HBsAg and isolated anti-HBc were found in this study. The I195M
mutation found in the surface gene could have been induced by immune pressure.
Although the number of ''vaccine escape'' mutants found in this cohort was low,
ongoing surveillance of breakthrough infections and escape mutants is still
needed.
PMID- 27613288
TI - Water treatment plant site location using rough set theory.
AB - Currently, advanced methods have been developed to select an appropriate site for
an engineering project. The ability to make a good decision in site selection can
help the engineers to reduce the expensive costs, which are very important in
large construction projects. In this paper, a new approach for site selection is
presented. This method is based on rough set theory which is a mathematical
theory presented by professor Pawlak. In this study, the results of the rough set
decision-making are compared with the results of the regression method in a
practical case study for the site location of a water treatment plant in Ardabil
Province in the northwest of Iran, to demonstrate that the rough set theory
provides a useful method for site selection. The results of practical studies
indicate that using this method for site selection decision-making can reduce
costs and prevent hazards that may happen due to civil engineering uncertainties.
PMID- 27613289
TI - Assessment of metals in cosmetics commonly used in Saudi Arabia.
AB - Cosmetics are one of the most important sources of releasing heavy metals.
Different varieties of chemicals are used in cosmetic products as ingredients and
some are used as preservatives. There are concerns regarding the presence of
harmful chemicals in these products. Among the harmful chemicals, cosmetic
products contain heavy metals. The present study was conducted to determine the
content of certain heavy metals in the products made in different countries and
marketed in Saudi Arabia. Thirty-one products of different brands or misbrands of
commonly used cosmetic products (hair cream, beauty cream, skin cream, hair food
formula, hair gel, whitening daily scrub, shampoo, shower gel, body care, body
lotion, hand wash, daily fairness, shaving cream, toothpaste, germ and beauty
soap, and cream soap) were purchased from local markets of Saudi Arabia. Samples
were analyzed to determine the concentrations of ten metals (lead, aluminum,
cadmium, cobalt, chromium, copper, manganese, nickel, mercury, and arsenic) using
inductively coupled plasma mass spectrometer (ICP-MS). Based on the maximum
concentrations, the heavy metal contents were arranged in the following
decreasing order: Al > Cu > Mn > Pb > Cr > Ni > Hg > Co > As > Cd in cream
products, Al > Pb > Cu > Cr > Mn > Ni > Hg > As > Co > Cd in shampoo products, Al
> Cu > Pb > Cr > Mn > Ni > As > Co > Hg > Cd in soap products, and Al > Cu > Mn >
Pb > Cr > Co > Ni > Cd > As > Hg in toothpaste products. Since the metal
concentrations may relate to specific brands, product type, color, or cost,
industrialist would have to check the raw materials before they are gathered into
the final products to track the source of these contaminants.
PMID- 27613290
TI - Bioavailability assessment of toxic metals using the technique "acid-volatile
sulfide (AVS)-simultaneously extracted metals (SEM)" in marine sediments
collected in Todos os Santos Bay, Brazil.
AB - This paper reports the bioavailability of the metals (cadmium, copper, zinc,
lead, and nickel) in sediment samples collected in seven stations from the Sao
Paulo Estuary, Todos os Santos Bay, Brazil. The bioavailability was determined by
employing the technique "acid-volatile sulfide (AVS) and simultaneously extracted
metal (SEM)". The elements cadmium, copper, lead, and zinc were determined using
differential pulse anodic stripping voltammetry (DPASV), while nickel was
quantified utilizing electrothermal atomic absorption spectrometry (ET AAS). The
accuracy of these methods was confirmed using a certified reference material of
estuarine sediment (NIST 1646). The sulfide was quantified using potentiometry
with selective electrode and the organic matter determination employing an
indirect volumetric method using potassium dichromate and iron(II) sulfate
solutions. The bioavailability of the metals was estimated by relationship
between the concentration of AVS and the sum of the concentrations of the
simultaneously extracted metals (SigmaSEM), considering a significant toxicity
when (SigmaSEM)/(AVS) is higher than 1. The bioavailability values in the seven
stations studied varied from 0.93 to 1.31 (June, 2014) and from 0.34 to 0.58
(September, 2014). These results demonstrated a critical condition of toxicity
(bioavailability >1) in six of the seven sediment samples collected during the
rainy season (June, 2014). In the other period (September, 2014), the
bioavailability was always lower than 1 for all sediment samples collected in the
seven stations. The individual values of the concentrations of the five metals
were compared with the parameters PEL (probable effects level) and TEL (threshold
effects level), which are commonly employed for characterization of ecological
risk in environmental systems. This comparison revealed that all metals have
concentrations lower than the PEL and only zinc and lead in some stations have
contents higher than the TEL. The bioavailability evaluation and the
concentrations achieved for the five elements in the sediments samples analyzed
demonstrated that the ecosystem studied does not present an environmental risk.
PMID- 27613292
TI - Climate change in Lagos state, Nigeria: what really changed?
AB - Our study revealed periodicities of 2.3 and 2.25 years in wet and dry seasons and
periodicities of 2 to 5 years on seasonal and annual timescales. Minimum
temperature (Tmin), maximum temperature (Tmax) and evaporation recorded increases
of 2.47, 1.37 and 28.37 %, respectively, but a reduction of 19.58 % in rainfall
on decadal timescale. Periodicity of 8 to 12 years was also observed in annual
Tmax. Cramer's test indicated a warming trend with significant Tmax increase in
February, April, July, August, October and November during 2000-2009 on decadal
monthly timescale, a significant decline in Summer rainfall but significant Tmax
increase in Spring, Autumn and Winter on decadal seasonal timescale. The low
correlation of rainfall with temperature parameters and evaporation indicates
that advection of moisture into Lagos State seems to be the dominant mechanism
controlling rainfall within the State alongside other tropical and extra-tropical
factors. In addition, our study revealed that the persistent state of minimum
temperature often precedes the arrival and reversal of the phase of maximum
temperature. Furthermore, our study also revealed that extreme and high variable
rainfalls, which are associated with the increased warming trend, had
periodicities of 1 to 3 years with a probability of 86.45 % of occurring every 3
years between April and September. It is recommended that government and private
sector should give financial and technical supports to climate researches in
order to appropriately inform policy making to improve the adaptive capacity and
resilience of Lagos State against climate change impacts and guard against
maladaptation.
PMID- 27613291
TI - Evaluating impacts using a BACI design, ratios, and a Bayesian approach with a
focus on restoration.
AB - Before-after-control-impact (BACI) designs are an effective method to evaluate
natural and human-induced perturbations on ecological variables when treatment
sites cannot be randomly chosen. While effect sizes of interest can be tested
with frequentist methods, using Bayesian Markov chain Monte Carlo (MCMC) sampling
methods, probabilities of effect sizes, such as a >=20 % increase in density
after restoration, can be directly estimated. Although BACI and Bayesian methods
are used widely for assessing natural and human-induced impacts for field
experiments, the application of hierarchal Bayesian modeling with MCMC sampling
to BACI designs is less common. Here, we combine these approaches and extend the
typical presentation of results with an easy to interpret ratio, which provides
an answer to the main study question-"How much impact did a management action or
natural perturbation have?" As an example of this approach, we evaluate the
impact of a restoration project, which implemented beaver dam analogs, on
survival and density of juvenile steelhead. Results indicated the probabilities
of a >=30 % increase were high for survival and density after the dams were
installed, 0.88 and 0.99, respectively, while probabilities for a higher increase
of >=50 % were variable, 0.17 and 0.82, respectively. This approach demonstrates
a useful extension of Bayesian methods that can easily be generalized to other
study designs from simple (e.g., single factor ANOVA, paired t test) to more
complicated block designs (e.g., crossover, split-plot). This approach is
valuable for estimating the probabilities of restoration impacts or other
management actions.
PMID- 27613294
TI - Alterations of Enteric Microbiota in Patients with a Normal Ileal Pouch Are
Predictive of Pouchitis.
AB - Objective: To examine whether patients with a mature normal pouch [> 1 year post
ileostomy closure] have microbial stool characteristics that can predict pouch
inflammation. Design: Patients undergoing pouch surgery were recruited
prospectively. Microbiota analysis of faecal samples was by 16S rRNA gene
pyrosequencing. All patients had a normal pouch at baseline [T1]. Those without
pouchitis during the first year of follow-up [T2] comprised the 'Normal Pouch
sustained' group and those who had experienced an episode of pouchitis comprised
the 'Pre-Pouchitis' group. Results: Twenty patients were recruited (age 53.6+/
13.1 years, pouch age [time from ileostomy closure] 8.1+/-5.1 years). Seven
patients developed pouchitis during follow-up [within 265+/-93.6 days] and they
were assigned to the Pre-Pouchitis group at T1: they had a decreased microbial
diversity at T1 compared with the Normal Pouch-sustained patients [n = 13]. The
Shannon diversity index for the Pre-Pouchitis patients was 3.4 vs 4.23 for the
Normal Pouch-sustained patients [p = 0.011]. There were no substantial group
differences in high taxonomic levels [order or above]. The genus Ruminococcus was
significantly decreased in the Pre-Pouchitis patients' samples compared with
those of the Normal Pouch-sustained patients (0.19% vs 0.78%, respectively, false
discovery rate [FDR] = 0.05). The linear discriminant analysis with effect size
estimation algorithm revealed that Lachnospira and Coprococcus genera were also
decreased among Pre-Pouchitis patients compared with Normal Pouch-sustained
patients [0.6% vs 1.95% and 2.1% vs 4%, respectively]. Conclusions: Patients with
a normal mature pouch may be predisposed to acute pouchitis when faecal microbial
diversity and certain microbial groups are decreased. These findings may aid in
risk stratification of those patients.
PMID- 27613293
TI - Making Sense of: Sensitization in Schizophrenia.
AB - Sensitization is defined as a process whereby repeated intermittent exposure to a
given stimulus results in an enhanced response at subsequent exposures. Next to
robust findings of an increased dopamine synthesis capacity in schizophrenia,
empirical data and neuroimaging studies support the notion that the mesolimbic
dopamine system of patients with schizophrenia is more reactive compared with
healthy controls. These studies led to the conceptualization of schizophrenia as
a state of endogenous sensitization, as stronger behavioral response and
increased dopamine release after amphetamine administration or exposure to stress
have been observed in patients with schizophrenia. These findings have also been
integrated into the neurodevelopmental model of the disorder, which assumes that
vulnerable neuronal circuits undergo progressive changes during puberty and young
adulthood that lead to manifest psychosis. Rodent and human studies have made an
attempt to identify the exact mechanisms of sensitization of the dopaminergic
system and its association with psychosis. Doing so, several epigenetic and
molecular alterations associated with dopamine release, neuroplasticity, and
cellular energy metabolism have been discovered. Future research aims at
targeting these key proteins associated with sensitization in schizophrenia to
enhance the knowledge of the pathophysiology of the illness and pave the way for
an improved treatment or even prevention of this severe psychiatric disorder.
PMID- 27613295
TI - The relationship between simple renal cysts and glomerular filtration rate in the
elderly.
AB - PURPOSE: This cross-sectional study aimed to examine the association between the
presence of simple renal cyst and glomerular filtration rate (GFR) in a group of
elderly patients. METHODS: This study included 207 elderly subjects residing in a
nursing home. All subjects underwent ultrasonography examination as well as serum
urea and creatinine measurements. Creatinine clearance was calculated according
to Cockroft-Gault formula. In addition, demographic data were recorded. RESULTS:
Sixty-six subjects had simple renal cysts, and cysts were more frequent among
male patients (43.1 vs. 28.2 %, p = 0.047). In addition, patients with renal
cysts were slightly older and had a slightly lower GFR. On the other hand,
patients with or without renal cysts did not differ with regard to renal sizes.
In univariate analysis, reduced GFR was associated with older age (81.2 +/- 5.9
vs. 75.7 +/- 5.1 years, p < 0.001) and was more frequent among females (69.2 vs.
52.9 %, p = 0.034). In addition, lower BMI, presence of cyst, lower mean renal
length, and lower mean renal thickness were associated with impaired GFR (p <
0.05 for all); however, number or bilaterality of the cysts were not linked with
deterioration of GFR. Multivariate analysis identified only female gender (OR
2.4, 95 % CI 1.1-5.1, p = 0.030), a small BMI (<25; OR 6.2, 95 % CI 2.4-15.5, p <
0.001), and advanced age as independent predictors of low GFR. Each year increase
in age results in OR 1.2 (95 % CI 1.1-1.3, p < 0.001). CONCLUSION: Presence of
simple renal cyst does not seem to have an effect on the decline in GFR in
elderly patients. Age-related increase in the incidence of renal cysts appears to
occur in geriatric population.
PMID- 27613296
TI - A Global eDNA Comparison of Freshwater Bacterioplankton Assemblages Focusing on
Large-River Floodplain Lakes of Brazil.
AB - With its network of lotic and lentic habitats that shift during changes in
seasonal connection, the tropical and subtropical large-river systems represent
possibly the most dynamic of all aquatic environments. Pelagic water samples were
collected from Brazilian floodplain lakes (total n = 58) in four flood-pulsed
systems (Amazon [n = 21], Araguaia [n = 14], Parana [n = 15], and Pantanal [n =
8]) in 2011-2012 and sequenced via 454 for bacterial environmental DNA using 16S
amplicons; additional abiotic field and laboratory measurements were collected
for the assayed lakes. We report here a global comparison of the bacterioplankton
makeup of freshwater systems, focusing on a comparison of Brazilian lakes with
similar freshwater systems across the globe. The results indicate a surprising
similarity at higher taxonomic levels of the bacterioplankton in Brazilian
freshwater with global sites. However, substantial novel diversity at the family
level was also observed for the Brazilian freshwater systems. Brazilian
freshwater bacterioplankton richness was relatively average globally. Ordination
results indicate that Brazilian bacterioplankton composition is unique from other
areas of the globe. Using Brazil-only ordinations, floodplain system
differentiation most strongly correlated with dissolved oxygen, pH, and
phosphate. Our data on Brazilian freshwater systems in combination with analysis
of a collection of freshwater environmental samples from across the globe offers
the first regional picture of bacterioplankton diversity in these important
freshwater systems.
PMID- 27613299
TI - [Report of the Dermatopathology Working Group : Berlin 2016].
PMID- 27613298
TI - Predicting the redox state and secondary structure of cysteine residues using
multi-dimensional classification analysis of NMR chemical shifts.
AB - A tool for predicting the redox state and secondary structure of cysteine
residues using multi-dimensional analyses of different combinations of nuclear
magnetic resonance (NMR) chemical shifts has been developed. A data set of
cysteine [Formula: see text], (13)C(alpha), (13)C(beta), (1)H(alpha), (1)H(N),
and (15)N(H) chemical shifts was created, classified according to redox state and
secondary structure, using a library of 540 re-referenced BioMagResBank (BMRB)
entries. Multi-dimensional analyses of three, four, five, and six chemical shifts
were used to derive rules for predicting the structural states of cysteine
residues. The results from 60 BMRB entries containing 122 cysteines showed that
four-dimensional analysis of the C(alpha), C(beta), H(alpha), and N(H) chemical
shifts had the highest prediction accuracy of 100 and 95.9 % for the redox state
and secondary structure, respectively. The prediction of secondary structure
using 3D, 5D, and 6D analyses had the accuracy of ~90 %, suggesting that H(N) and
[Formula: see text] chemical shifts may be noisy and made the discrimination
worse. A web server (6DCSi) was established to enable users to submit NMR
chemical shifts, either in BMRB or key-in formats, for prediction. 6DCSi displays
predictions using sets of 3, 4, 5, and 6 chemical shifts, which shows their
consistency and allows users to draw their own conclusions. This web-based tool
can be used to rapidly obtain structural information regarding cysteine residues
directly from experimental NMR data.
PMID- 27613300
TI - [Annual report of the working group on informatics, innovative imaging, and
biobanking of the German society for pathology].
PMID- 27613301
TI - [Report on the meeting of the Hematopathology Working Group].
PMID- 27613297
TI - Dermoscopy in General Dermatology: A Practical Overview.
AB - Over the last few years, dermoscopy has been shown to be a useful tool in
assisting the noninvasive diagnosis of various general dermatological disorders.
In this article, we sought to provide an up-to-date practical overview on the use
of dermoscopy in general dermatology by analysing the dermoscopic differential
diagnosis of relatively common dermatological disorders grouped according to
their clinical presentation, i.e. dermatoses presenting with erythematous
desquamative patches/plaques (plaque psoriasis, eczematous dermatitis, pityriasis
rosea, mycosis fungoides and subacute cutaneous lupus erythematosus),
papulosquamous/papulokeratotic dermatoses (lichen planus, pityriasis rosea,
papulosquamous sarcoidosis, guttate psoriasis, pityriasis lichenoides chronica,
classical pityriasis rubra pilaris, porokeratosis, lymphomatoid papulosis,
papulosquamous chronic GVHD, parakeratosis variegata, Grover disease, Darier
disease and BRAF-inhibitor-induced acantholytic dyskeratosis), facial
inflammatory skin diseases (rosacea, seborrheic dermatitis, discoid lupus
erythematosus, sarcoidosis, cutaneous leishmaniasis, lupus vulgaris, granuloma
faciale and demodicidosis), acquired keratodermas (chronic hand eczema, palmar
psoriasis, keratoderma due to mycosis fungoides, keratoderma resulting from
pityriasis rubra pilaris, tinea manuum, palmar lichen planus and aquagenic palmar
keratoderma), sclero-atrophic dermatoses (necrobiosis lipoidica, morphea and
cutaneous lichen sclerosus), hypopigmented macular diseases (extragenital guttate
lichen sclerosus, achromic pityriasis versicolor, guttate vitiligo, idiopathic
guttate hypomelanosis, progressive macular hypomelanosis and postinflammatory
hypopigmentations), hyperpigmented maculopapular diseases (pityriasis versicolor,
lichen planus pigmentosus, Gougerot-Carteaud syndrome, Dowling-Degos disease,
erythema ab igne, macular amyloidosis, lichen amyloidosus, friction melanosis,
terra firma-forme dermatosis, urticaria pigmentosa and telangiectasia macularis
eruptiva perstans), itchy papulonodular dermatoses (hypertrophic lichen planus,
prurigo nodularis, nodular scabies and acquired perforating dermatosis),
erythrodermas (due to psoriasis, atopic dermatitis, mycosis fungoides, pityriasis
rubra pilaris and scabies), noninfectious balanitis (Zoon's plasma cell
balanitis, psoriatic balanitis, seborrheic dermatitis and non-specific balanitis)
and erythroplasia of Queyrat, inflammatory cicatricial alopecias (scalp discoid
lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia and
folliculitis decalvans), nonscarring alopecias (alopecia areata,
trichotillomania, androgenetic alopecia and telogen effluvium) and scaling
disorders of the scalp (tinea capitis, scalp psoriasis, seborrheic dermatitis and
pityriasis amiantacea).
PMID- 27613302
TI - [Tumorigenesis from a pathological perspective : Tumor spread and epigenetically
regulated genes in bladder cancer].
AB - The article describes the tumorigenesis of bladder cancer from a pathological
perspective in three dimensions: morphology, genetics and epigenetics. Field
cancerization and tumor cell migration/seeding are the two main hypotheses used
for explaining synchronous and metachronous tumors in the urinary tract. By
detailed histological mapping of completely embedded cystectomy specimens we
found a single tumor focus in nearly 2/3 of the bladders accompanied by
surrounding preinvasive carcinoma in situ. We substantiated our findings by
studies analyzing TP53 mutations and loss of heterozygosity in various tumor
sites. Identical TP53 mutations suggested a clonal relationship of the tumor
foci. In situ lineage tracing via cytochrome C oxidase and succinate
dehydrogenase enzyme histochemistry and subsequent mitochondrial DNA mutation
analysis for definitive evidence of a clonal relationship in bladder tumors
remained inconclusive. We found indications for both theories but intraurothelial
migration/seeding was more prominent.A further mechanism in tumorigenesis is gene
inactivation by epigenetic DNA methylation. We analyzed DNA methylation of
various genes, which had previously been found by RNA expression analysis to be
downregulated in bladder cancer. Most importantly, epigenetically silenced ITIH5
was associated with early relapse in pT1 high grade tumors and functionally
showed an enhanced invasive metastatic phenotype in tumor cells, suggesting a
putative tumor suppressive role. Thus, epigenetic gene silencing is an additional
mechanism of tumorigenesis especially in tumor progression.
PMID- 27613304
TI - Record demand on NHS is pushing services above safe thresholds, report warns.
PMID- 27613303
TI - [Predictive molecular pathological stratification of hematological neoplasms].
AB - The comprehensive sequencing of the complete genome of various hematological
neoplasms has allowed an in-depth insight into the genomic heterogeneity and led
to the discovery of new genetic aberrations, which seem to be very promising as
therapeutic target structures. The molecular target structures of new therapeutic
agents are, however, nearly exclusively proteins and cannot be directly
identified with nucleic acid-based investigation methods. There is a great
potential in investigations at the protein level that reflect an expression of
the target protein and/or alterations of the signal cascade in tumor cells. In
this context immunohistochemistry is a procedure that can deliver the decisive
information using mutation, phosphorylation and glycosylation-specific primary
antibodies. This study was carried out to comprehensively investigate the
diagnostic utilization of such antibodies for hematological neoplasms. The
studies summarized in this article emphasize the significance of tissue-based
diagnostic approaches at the protein level and are suitable for use in patient
selection for targeted treatment. A particular success of these studies was to
make an essential contribution to the predictive diagnostics of multiple myeloma.
PMID- 27613305
TI - Decreased activation of placental mTOR family members is associated with the
induction of intrauterine growth restriction by secondhand smoke in the mouse.
AB - Cigarette smoke is known to be a risk for the development of intrauterine growth
restriction (IUGR). Our objective was to assess the effects of secondhand smoke
(SHS) during pregnancy and to what extent it regulates the activation of mTOR
family members and murine trophoblast invasion. Mice were treated to SHS for 4
days. Placental and fetal weights were recorded at the time of necropsy.
Immunohistochemistry was used to determine the level of placental trophoblast
invasion. Western blots were utilized to assess the activation of caspase 3,
XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared
to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal
(2.3-fold) weights (p < 0.05); (2) decreased trophoblast invasion; (3)
significantly decreased active caspase 3 (1.3-fold; p < 0.02) and increased
active XIAP (3.6-fold; p < 0.05) in the placenta; and (4) a significant decrease
in the activation of placental mTOR (2.1-fold; p < 0.05), p70 (1.9-fold; p <
0.05) and 4EBP1 (1.3-fold; p < 0.05). Confirmatory in vitro experiments revealed
decreased trophoblast invasion when SW71 cells were treated with 0.5 or 1.0 %
cigarette smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR
via decreased activation of the mTOR family of proteins in the placenta.
Increased activation of the placental XIAP protein could be a survival mechanism
for abnormal trophoblast cells during SHS exposure. Further, CSE reduced
trophoblast invasion, suggesting a direct causative effect of smoke on
susceptible trophoblast cells involved in IUGR progression. These results provide
important insight into the physiological consequences of SHS exposure and smoke
mediated placental disease.
PMID- 27613306
TI - Distinguishing Aspartic and Isoaspartic Acids in Peptides by Several Mass
Spectrometric Fragmentation Methods.
AB - Six ion fragmentation techniques that can distinguish aspartic acid from its
isomer, isoaspartic acid, were compared. MALDI post-source decay (PSD), MALDI 157
nm photodissociation, tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP)
charge tagging in PSD and photodissociation, ESI collision-induced dissociation
(CID), electron transfer dissociation (ETD), and free-radical initiated peptide
sequencing (FRIPS) with CID were applied to peptides containing either aspartic
or isoaspartic acid. Diagnostic ions, such as the y-46 and b+H2O, are present in
PSD, photodissociation, and charge tagging. c*+57 and z-57 ions are observed in
ETD and FRIPS experiments. For some molecules, aspartic and isoaspartic acid
yield ion fragments with significantly different intensities. ETD and charge
tagging appear to be most effective at distinguishing these residues. Graphical
Abstract ?.
PMID- 27613308
TI - Quantitative Raman Spectroscopy when the Signal-to-Noise is Below the Limit of
Quantitation due to Fluorescence Interference: Advantages of a Moving Window
Sequentially Shifted Excitation Approach.
AB - Raman spectroscopy is a useful analytical tool. However, its application is often
limited because shot noise from fluorescence obscures the Raman signal. In such
cases, quantitative analysis is not possible when the signal-to-noise ratio (SNR)
drops below two. A method is described for performing quantitative Raman
spectroscopy that not only removes fluorescence backgrounds, but also results in
a significant improvement in the SNR. The Raman data is extracted using a moving
window sequentially shifted excitation algorithm. To demonstrate the capabilities
of the method, a binary mixture of two analytes at varying concentrations is
quantified in the presence of a highly fluorescent dye. Linear calibration plots
were constructed and validated for the binary model using individual Raman peaks
with SNR ranging from 0.073-12.6; r(2) values are greater than 0.96 in all cases,
with all but the weakest peaks yielding values greater than 0.997. The presented
method demonstrates a universal and autonomous approach for the quantitative
analysis of highly fluorescent samples via Raman spectroscopy. The lower limit on
the SNR ratio for quantitative Raman analysis with the described method is 0.1.
In order to assess the effectiveness of the presented method, the entire set of
experiments was also processed using the more common shifted excitation Raman
difference spectroscopy (SERDS) approach. The advantages of the proposed method
over SERDS are demonstrated for both the detection limit and the SNR of the
processed spectra.
PMID- 27613309
TI - An Improved Spectral Background Subtraction Method Based on Wavelet Energy.
AB - Most spectral background subtraction methods rely on the difference in frequency
response of background compared with characteristic peaks. It is difficult to
extract accurately the background components from the spectrum when
characteristic peaks and background have overlaps in frequency domain. An
improved background estimation algorithm based on iterative wavelet transform
(IWT) is presented. The wavelet entropy principle is used to select the best
wavelet basis. A criterion based on wavelet energy theory to determine the
optimal iteration times is proposed. The case of energy dispersive X-ray
spectroscopy is discussed for illustration. A simulated spectrum with a prior
known background and an experimental spectrum are tested. The processing results
of the simulated spectrum is compared with non-IWT and it demonstrates the
superiority of the IWT. It has great significance to improve the accuracy for
spectral analysis.
PMID- 27613307
TI - Volume and its relationship to cardiac output and venous return.
AB - Volume infusions are one of the commonest clinical interventions in critically
ill patients yet the relationship of volume to cardiac output is not well
understood. Blood volume has a stressed and unstressed component but only the
stressed component determines flow. It is usually about 30 % of total volume.
Stressed volume is relatively constant under steady state conditions. It creates
an elastic recoil pressure that is an important factor in the generation of blood
flow. The heart creates circulatory flow by lowering the right atrial pressure
and allowing the recoil pressure in veins and venules to drain blood back to the
heart. The heart then puts the volume back into the systemic circulation so that
stroke return equals stroke volume. The heart cannot pump out more volume than
comes back. Changes in cardiac output without changes in stressed volume occur
because of changes in arterial and venous resistances which redistribute blood
volume and change pressure gradients throughout the vasculature. Stressed volume
also can be increased by decreasing vascular capacitance, which means recruiting
unstressed volume into stressed volume. This is the equivalent of an auto
transfusion. It is worth noting that during exercise in normal young males,
cardiac output can increase five-fold with only small changes in stressed blood
volume. The mechanical characteristics of the cardiac chambers and the
circulation thus ultimately determine the relationship between volume and cardiac
output and are the subject of this review.
PMID- 27613311
TI - The effect of glucose-coated gold nanoparticles on radiation bystander effect
induced in MCF-7 and QUDB cell lines.
AB - Due to biocompatibility and relative non-toxic nature, gold nanoparticles (GNPs)
have been studied widely to be employed in radiotherapy as radio-sensitizer. On
the other hand, they may enhance radiation-induced bystander effect (RIBE), which
causes radiation adverse effects in non-irradiated normal cells. The present
study was planned to investigate the possibility of augmenting the RIBE
consequence of applying glucose-coated gold nanoparticles (Glu-GNPs) to target
cells. Glu-GNPs were synthesized and utilized to treat MCF7 and QUDB cells. The
treated cells were irradiated with 100 kVp X-rays, and their culture media were
transferred to non-irradiated bystander cells. Performing MTT cellular
proliferation test and colony formation assay, percentage cell viability and
survival fraction of bystander cells were determined, respectively, and were
compared to control bystander cells which received culture medium from irradiated
cells without Glu-GNPs. Glu-GNPs decreased the cell viability and survival
fraction of QUDB bystander cells by as much as 13.2 and 11.5 %, respectively (P <
0.02). However, the same end points were not changed by Glu-GNPs in MCF-7
bystander cells. Different RIBE responses were observed in QUDB and MCF7 loaded
with Glu-GNPs. Glu-GNPs increased the RIBE in QUDB cells, while they had no
effects on RIBE in MCF7 cells. As opposed to QUDB cells, the RIBE in MCF7 cells
did not change in the dose range of 0.5-10 Gy. Therefore, it might be a constant
effect and the reason of not being increased by Glu-GNPs.
PMID- 27613313
TI - Synovial osteochondromatosis of the shoulder: Case report and literature review.
PMID- 27613312
TI - Cerebral autoregulation and symptoms of orthostatic hypotension in familial
dysautonomia.
AB - Familial dysautonomia is an inherited autonomic disorder with afferent baroreflex
failure. We questioned why despite low blood pressure standing, surprisingly few
familial dysautonomia patients complain of symptomatic hypotension or have
syncope. Using transcranial Doppler ultrasonography of the middle cerebral
artery, we measured flow velocity (mean, peak systolic, and diastolic), area
under the curve, pulsatility index, and height of the dictrotic notch in 25
patients with familial dysautonomia and 15 controls. In patients, changing from
sitting to a standing position, decreased BP from 124 +/- 4/64 +/- 3 to 82 +/-
3/37 +/- 2 mmHg (p < 0.0001, for both). Despite low BP, all patients denied
orthostatic symptoms. Middle cerebral artery velocity fell minimally, and the
magnitude of the reductions were similar to those observed in healthy controls,
in whom BP upright did not fall. While standing, patients had a greater fall in
cerebrovascular resistance (p < 0.0001), an increase in pulsatility (p < 0.0001),
and a deepening of the dicrotic notch (p = 0.0010), findings all consistent with
low cerebrovascular resistance. No significant changes occurred in controls.
Patients born with baroreflex deafferentation retain the ability to buffer wide
fluctuations in BP and auto-regulate cerebral blood flow. This explains how they
can tolerate extremely low BPs standing that would otherwise induce syncope.
PMID- 27613310
TI - An overview of rapamycin: from discovery to future perspectives.
AB - Rapamycin is an immunosuppressive metabolite produced from several actinomycete
species. Besides its immunosuppressive activity, rapamycin and its analogs have
additional therapeutic potentials, including antifungal, antitumor,
neuroprotective/neuroregenerative, and lifespan extension activities. The core
structure of rapamycin is derived from (4R,5R)-4,5-dihydrocyclohex-1-ene
carboxylic acid that is extended by polyketide synthase. The resulting linear
polyketide chain is cyclized by incorporating pipecolate and further decorated by
post-PKS modification enzymes. Herein, we review the discovery and biological
activities of rapamycin as well as its mechanism of action, mechanistic target,
biosynthesis, and regulation. In addition, we introduce the many efforts directed
at enhancing the production of rapamycin and generating diverse analogs and also
explore future perspectives in rapamycin research. This review will also
emphasize the remarkable pilot studies on the biosynthesis and production
improvement of rapamycin by Dr. Demain, one of the world's distinguished
scientists in industrial microbiology and biotechnology.
PMID- 27613314
TI - Characteristics of cadmium remobilization in tributary sediments in Three Gorges
Reservoir using chemical sequential extraction and DGT technology.
AB - The Three Gorges Reservoir (TGR) is the largest reservoir in China. Cadmium (Cd)
is a primary pollutant in the TGR, and its speciation and bioavailability have
attracted extensive attention since TGR submergence. In this study, Chelex-100
DGT (diffusive gradient in thin films) and the sequential extraction method were
used to investigate the bioavailable Cd in sediments obtained from a typical
tributary (Meixi) and mainstream (Yangtze) in the TGR. The total Cd
concentrations in sediments of the four stations were also determined. In
comparison to the concentrations of labile Cd measured by DGT (CDGT-Cd) in four
profiles, CJ and MX-upstream/downstream were at potential risk for Cd release
from surface sediments using the apparent diffusion flux across the interface
numerical model. The order of CDGT-Cd in surface sediments was as follows: CJ >
MX-downstream > MX-upstream > MX-midstream. Additionally, a positive correlation
was demonstrated between CDGT-Cd and Cd in the exchangeable fraction (F1) in the
surface sediments, indicating that Cd in the exchangeable fraction was readily
captured by DGT. A negative correlation was observed between CDGT-Cd and CDGT-Fe,
CDGT-Mn in the sediment-water-interface (SWI), suggesting that Fe/Mn oxides did
not control the release of labile-Cd from sediments. Furthermore, a positive
correlation existed between the CDGT-Cd in the surface sediments and Cd in the
oxidizable fraction (F3), illustrating that Cd sorbed or bound with organic
matter or sulfide was labile and released into the water phase from the surface
sediments. A dark area was found in the AgI gel, which further demonstrated that
Cd simultaneously was released with sulfide in this area.
PMID- 27613315
TI - Cu-Zn isotope constraints on the provenance of air pollution in Central Europe:
Using soluble and insoluble particles in snow and rime.
AB - Copper (Cu) and zinc (Zn) isotope ratios can be used to fingerprint sources and
dispersion pathways of pollutants in the environment. Little is known, however,
about the potential of delta65Cu and delta66Zn values in liquid and solid forms
of atmospheric deposition to distinguish between geogenic, industrial, local and
remote sources of these potentially toxic base metals. Here we present Cu-Zn
deposition fluxes at 10 mountain-top sites in the Czech Republic, a region
affected by extremely high industrial emission rates 25 years ago. Additionally,
we monitored isotope composition of Cu and Zn in vertical and horizontal
atmospheric deposition at two sites. We compared delta65Cu and delta66Zn values
in snow and rime, extracted by diluted HNO3 and concentrated HF. Cu and Zn
isotope signatures of industrial pollution sources were also determined. Cu and
Zn deposition fluxes at all study sites were minute. The mean delta65Cu value of
atmospheric deposition (-0.070/00) was higher than the mean delta65Cu value of
pollution sources (-1.170/00). The variability in delta65Cu values of atmospheric
deposition was lower, compared to the pollution sources. The mean delta66Zn value
of atmospheric deposition (-0.090/00) was slightly higher than the mean delta66Zn
value of pollution sources (-0.230/00). The variability in delta66Zn values of
atmospheric deposition was indistinguishable from that of pollution sources. The
largest isotope differences (0.350/00) were observed between the insoluble and
soluble fractions of atmospheric deposition. These differences may result from
different sources of Cu/Zn for each fraction. The difference in isotope
composition of soluble and insoluble particles appears to be a promising tool for
pollution provenance studies in Central Europe.
PMID- 27613316
TI - Homeostatic regulation of copper in a marine fish simulated by a physiologically
based pharmacokinetic model.
AB - Copper (Cu) is an essential yet potentially toxic metal, thus delicate
homeostatic controls are developed in the fish. In this study, a physiologically
based pharmacokinetic (PBPK) model was developed to simulate the homeostatic
regulation of Cu in a marine fish (Terapon jarbua) under dietary and waterborne
exposures. In this model, fish were schematized as a six-compartment model, with
the intestine being divided into two sub-compartments (chyme and gut wall). The
blood was assumed to be the "carrier" distributing Cu into different
compartments. The transfer rates between different compartments were determined
in fish during Cu exposure (20 d) and depuration (20 d). The differences in Cu
transfer from chyme to gut wall between dietary and waterborne treatments
suggested that the intestine regulated the dietary uptake and re-absorption of Cu
from the chyme. The extremely low uptake rate constant (0.0013 d-1) for gills
under waterborne exposure indicated that gills strongly restricted Cu uptake from
the ambient water. For both treatments, the liver had considerable input rate
through the enterohepatic circulation and comparably high exchange rate with the
blood, suggesting that the liver can efficiently accumulate newly absorbed Cu.
The differences in Cu output from the liver between dietary and waterborne
treatments suggested that it can effectively regulate the redistribution of Cu.
All of these observations demonstrated that the liver played the central role in
Cu homeostasis by serving as the main depository and distributing center.
Modeling results also indicated that renal and branchial excretion was of minor
importance, whereas biliary excretion combined with defecation played the most
important role in whole-body Cu elimination in marine fish. The effective
regulation by the "Blood-Liver-Intestine" cycle could be the main reason for the
relatively low levels of Cu in fish.
PMID- 27613317
TI - Regional accumulation characteristics of cadmium in vegetables: Influencing
factors, transfer model and indication of soil threshold content.
AB - A regional investigation in the Youxian prefecture, southern China, was conducted
to analyze the impact of environmental factors including soil properties and
irrigation in conjunction with the use of fertilizers on the accumulation of Cd
in vegetables. The Cd transfer potential from soil to vegetable was provided by
the plant uptake factor (PUF), which varied by three orders of magnitude and was
described by a Gaussian distribution model. The soil pH, content of soil organic
matter (SOM), concentrations of Zn in the soil, pH of irrigation water and
nitrogenous fertilizers contributed significantly to the PUF variations. A path
model analysis, however, revealed the principal control of the PUF values
resulted from the soil pH, soil Zn concentrations and SOM. Transfer functions
were developed using the total soil Cd concentrations, soil pH, and SOM. They
explained 56% of the variance for all samples irrespective of the vegetable
genotypes. The transfer functions predicted the probability of exceeding China
food safety standard concentrations for Cd in four major consumable vegetables
under different soil conditions. Poor production practices in the study area
involved usage of soil with pH values <= 5.5, especially for the cultivation of
Raphanus sativus L., even with soil Cd concentrations below the China soil
quality standard. We found the soil standard Cd concentrations for cultivating
vegetables was not strict enough for strongly acidic (pH <= 5.5) and SOM-poor
(SOM <= 10 g kg-1) soils present in southern China. It is thus necessary to
address the effect of environmental variables to generate a suitable Cd threshold
for cultivated soils.
PMID- 27613318
TI - Deep challenges for China's war on water pollution.
AB - China's Central government has released an ambitious plan to tackle the nation's
water pollution crisis. However, this is inhibited by a lack of data,
particularly for groundwater. We compiled and analyzed water quality
classification data from publicly available government sources, further revealing
the scale and extent of the crisis. We also compiled nitrate data in shallow and
deep groundwater from a range of literature sources, covering 52 of China's
groundwater systems; the most comprehensive national-scale assessment yet.
Nitrate pollution at levels exceeding the US EPA's maximum contaminant level (10
mg/L NO3N) occurs at the 90th percentile in 25 of 36 shallow aquifers and 10 out
of 37 deep or karst aquifers. Isotopic compositions of groundwater nitrate
(delta15N and delta18ONO3 values ranging from -14.90/00 to 35.50/00 and -8.10/00
to 51.00/00, respectively) indicate many nitrate sources including soil nitrogen,
agricultural fertilizers, untreated wastewater and/or manure, and locally show
evidence of de-nitrification. From these data, it is clear that contaminated
groundwater is ubiquitous in deep aquifers as well as shallow groundwater (and
surface water). Deep aquifers contain water recharged tens of thousands of years
before present, long before widespread anthropogenic nitrate contamination. This
groundwater has therefore likely been contaminated due to rapid bypass flow along
wells or other conduits. Addressing the issue of well condition is urgently
needed to stop further pollution of China's deep aquifers, which are some of
China's most important drinking water sources. China's new 10-point Water
Pollution Plan addresses previous shortcomings, however, control and remediation
of deep groundwater pollution will take decades of sustained effort.
PMID- 27613319
TI - Role of mariculture in the loading and speciation of mercury at the coast of the
East China Sea.
AB - The effects of mariculture on mercury (Hg) contamination and speciation in water,
sediment and cultured fish in a typical mariculture zone located in Xiangshan
bay, Zhejiang province, east China, were studied. Water, sediment and fish
samples were collected from mariculture sites (MS) and from corresponding
reference sites (RS) 2500 m away from the MS. The THg concentration in overlying
water in Xiangshan bay reached as high as 16.6 +/- 19.5 ng L-1, indicating that
anthropogenic sources in this bay may contribution on Hg contamination in
overlying water. Mariculture activities resulted in an increase in THg
concentration in water from surface and bottom layers, which may be attributed to
the discharge of domestic sewage and the accumulation of unconsumed fish feed and
fish excreta in the benthic environment. Methylmercury (MeHg) concentrations in
the bottom layer of overlying water and top surface layer of porewater underneath
MS were higher than at RS, implying that mariculture activities promote Hg
methylation in the interface between sediments and water. In addition, the
concentrations of MeHg in sediment and porewater were significantly higher in
summer than winter. It was observed that THg and MeHg contents in the muscle of
blackhead seabream (Acanthopagrus schlegelii) (fed by the trash fish) were
significantly higher (p < 0.001) than those in red snapper (Lutjanus campechanus)
or perch (Perca fluviatilis) (fed by pellet fish feed). The THg and MeHg
concentrations in the fish meat were closely related to the feeding mode, which
indicate that fish feed rather than environmental media is the major pathway for
Hg accumulation in fish muscle.
PMID- 27613320
TI - Evaluating the predictability of PM10 grades in Seoul, Korea using a neural
network model based on synoptic patterns.
AB - As of November 2014, the Korean Ministry of Environment (KME) has been
forecasting the concentration of particulate matter with diameters <= 10 MUm
(PM10) classified into four grades: low (PM10 <= 30 MUg m-3), moderate (30 < PM10
<= 80 MUg m-3), high (80 < PM10 <= 150 MUg m-3), and very high (PM10 > 150 MUg m
3). The KME operational center generates PM10 forecasts using statistical and
chemistry-transport models, but the overall performance and the hit rate for the
four PM10 grades has not previously been evaluated. To provide a statistical
reference for the current air quality forecasting system, we have developed a
neural network model based on the synoptic patterns of several meteorological
fields such as geopotential height, air temperature, relative humidity, and wind.
Hindcast of the four PM10 grades in Seoul, Korea was performed for the cold
seasons (October-March) of 2001-2014 when the high and very high PM10 grades are
frequently observed. Because synoptic patterns of the meteorological fields are
distinctive for each PM10 grade, these fields were adopted and quantified as
predictors in the form of cosine similarities to train the neural network model.
Using these predictors in conjunction with the PM10 concentration in Seoul from
the day before prediction as an additional predictor, an overall hit rate of 69%
was achieved; the hit rates for the low, moderate, high, and very high PM10
grades were 33%, 83%, 45%, and 33%, respectively. Our findings also suggest that
the synoptic patterns of meteorological variables are reliable predictors for the
identification of the favorable conditions for each PM10 grade, as well as for
the transboundary transport of PM10 from China. This evaluation of PM10
predictability can be reliably used as a statistical reference and further,
complement to the current air quality forecasting system.
PMID- 27613321
TI - Cytotoxicity and genotoxicity induced in vitro by solvent-extractable organic
matter of size-segregated urban particulate matter.
AB - Three organic fractions of different polarity, including a non polar organic
fraction (NPOF), a moderately polar organic fraction (MPOF), and a polar organic
fraction (POF) were obtained from size-segregated (<0.49, 0.49-0.97, 0.97-3 and
>3 MUm) urban particulate matter (PM) samples, and tested for cytotoxicity and
genotoxicity using a battery of in vitro assays. The cytotoxicity induced by the
organic PM fractions was measured by the mitochondrial dehydrogenase (MTT) cell
viability assay applied on MRC-5 human lung epithelial cells. DNA damages were
evaluated through the comet assay, determination of the poly(ADP-Ribose)
polymerase (PARP) activity, and the oxidative DNA adduct 8-hydroxy-deoxyguanosine
(8-OHdG) formation, while pro-inflammatory effects were assessed by determination
of the tumor necrosis factor-alpha (TNF-alpha) mediator release. In addition, the
Sister Chromatid Exchange (SCE) inducibility of the solvent-extractable organic
matter was measured on human peripheral lymphocyte. Variations of responses were
assessed in relation to the polarity (hence the expected composition) of the
organic PM fractions, particle size, locality, and season. Organic PM fractions
were found to induce rather comparable Cytotoxicity and genotoxicity of PM
appeared to be rather independent from the polarity of the extractable organic PM
matter (EOM) with POF often being relatively more toxic than NPOF or MPOF. All
assays indicated stronger mass-normalized bioactivity for fine than coarse
particles peaking in the 0.97-3 and/or the 0.49-0.97 MUm size ranges.
Nevertheless, the air volume-normalized bioactivity in all assays was highest for
the <0.49 MUm size range highlighting the important human health risk posed by
the inhalation of these quasi-ultrafine particles.
PMID- 27613322
TI - Accumulation of polybrominated diphenyl ethers in the brain compared with the
levels in other tissues among different vertebrates from an e-waste recycling
site.
AB - This study aimed to investigate the accumulation of polybrominated diphenyl
ethers (PBDEs) in the brain compared with that in other tissues among different
vertebrates. We collected mice, chickens, ducks, frogs, and fish from an e-waste
recycling region in Taizhou, China, and measured PBDE concentrations in brain,
liver and muscle tissues. The levels of PBDE in the tissues of mice, chickens,
ducks, frogs and fish ranged 0.45-206, 0.06-18.8, 1.83-112, 2.75-108, and 0.02
32.0 ng/g wet weight, respectively. Preferential distribution in the liver and
muscle relative to the brain was observed for PBDEs in mice, chickens, ducks and
frogs. However, a high retention in the brain compared to the liver and muscle
was observed in fish. Comparison of the brain/liver concentration (B/L) ratios
revealed differences in PBDEs accumulation in the brain among these vertebrates.
PBDEs accumulation in the brain was greatest in fish, followed by frogs, while
the lowest accumulation occurred in the brains of mammals and birds. The findings
apparently coincided with the evolution of the blood-brain barrier (BBB) across
vertebrates, i.e. the BBB of fish might be less efficient than those of mammals,
birds and amphibian. Low brominated congeners (such as BDE-28, BDE-47 and BDE-99)
were predominant in the brains of investigated vertebrates, whereas BDE-209 was
most abundant in liver and muscle tissues of mice, chickens and ducks.
Significant differences in B/L ratios among PBDE congeners were found in both
mice and chickens (p < 0.05). Particularly in mice, the B/L ratios of PBDE
congeners presented a declining trend with increased bromine number. Our findings
suggested that low brominated congeners might have a higher capacity to penetrate
the BBB and accumulate in the brain, whereas high brominated congeners such as
BDE-209 might have less potency to pass through the barrier. Further experimental
studies are needed to confirm our findings.
PMID- 27613323
TI - Longitudinal occurrence of methylmercury in terrestrial ecosystems of the Tibetan
Plateau.
AB - Methylmercury (MeHg), a neurotoxin, is a global concern because of its potential
risk to human and ecological health. Elevated mercury (Hg) concentrations were
recently reported in the Tibetan Plateau (TP) due to increasing Hg input from
distant regions, yet little is known about MeHg production and distribution in
the terrestrial ecosystems of the TP. Here, we report longitudinal occurrence of
MeHg and the factors regulating net MeHg production in 23 grassland sites from
eastern to western TP. The soil MeHg content varied from 0.002 to 0.058 ng g-1,
with different distribution patterns between the eastern and western TP. There
was a positive correlation between the MeHg concentration and the longitude after
90 degrees E, which is similar to the distribution patterns of the total mercury
(THg), water and organic carbon in this region. Average MeHg concentration in
topsoil is generally higher than that in subsoil. Our results show that MeHg
concentration in soils of the TP is directly affected by soil water, potential
microbial methylators and THg, while indirectly regulated by soil organic carbon
through the microbial community and the longitude-dependent precipitation through
soil water. Our study suggests that soil water is the most important driver
regulating net MeHg production in the grasslands of the TP. These findings have
important implications for unraveling the mechanism of net production of MeHg in
high-altitude environments.
PMID- 27613324
TI - Mercury risk assessment combining internal and external exposure methods for a
population living near a municipal solid waste incinerator.
AB - Risk assessments for human health have been conducted for municipal solid waste
incinerators (MSWIs) in many western countries, whereas only a few risk
assessments have been performed for MSWIs in developing countries such as China
where the use of waste incineration is increasing rapidly. To assess the mercury
exposure risks of a population living near the largest MSWI in South China, we
combined internal exposure and external exposure assessment with an individual
specific questionnaire. The mercury concentrations in air, soil, and locally
collected food around the MSWI were assessed. The total mercury (T-Hg) and
methylmercury (MeHg) of 447 blood samples from a control group, residential
exposure group, and MSWI workers were measured. The internal and external
exposures of the subject population were analyzed. Significant difference in MeHg
concentrations was observed between the control group and the exposed group,
between the control group and the MSWI workers, and between the exposed group and
the MSWI workers (median levels: 0.70 MUg/L, 0.81 MUg/L, and 1.02 MUg/L for the
control group, exposed group, and MSWI workers, respectively). The MeHg/T-Hg
ratio was 0.51 +/- 0.19, 0.59 +/- 0.17 and 0.58 +/- 0.25, respectively. Multiple
linear regression analysis indicated that MeHg concentrations were positively
correlated with the gaseous mercury in the air. Combining internal and external
exposure assessment showed that the direct contribution of MSWI emissions was
minor compared with the dietary contribution. The external and internal exposures
were well matched with each other. This study also suggested that an integrated
method combining internal and external exposure assessment with an individual
specific questionnaire is feasible to assess the risks for a population living
near a MSWI.
PMID- 27613325
TI - Assessment of mobilization of labile phosphorus and iron across sediment-water
interface in a shallow lake (Hongze) based on in situ high-resolution
measurement.
AB - The internal loading of P is reported to be the main factor initiating algal
blooms. However, there are only a few reports on the dynamic variation of labile
P in the sediment and overlying water during the decomposition of algal. In
addition, the widely perceived relationship between labile P and Fe was not
supported by in situ obtained values in freshwater. Consequently, the in situ
simultaneous measurement of diffusion gradients in thin-film techniques (DGT) was
applied on a large scale to detect the mechanisms of labile P and Fe in a typical
shallow lake (Lake Hongze). The newly developed ZrO-DGT and ZrO-Chelex DGT were
combined to obtain the concentration of labile P and Fe. Results showed that
decomposition of algal might be the main contributor for the concentration dots
and peaks of labile P in sediment profiles, as well as for the high values on the
horizontal heterogeneity index of labile P at the depth of 0-30 mm of the
sediment. Moreover, there existed significant difference between the apparent
diffusion fluxes of labile P and Fe across the sediment-water interface which
obtained from June sampling and October sampling. The results of apparent
diffusion flux in two periods indicated the sediments changed from "sink" to
"source" for labile P, especially at Sites 4-8, 10, 13-14, and 18. However, the
role of the labile Fe has no significantly variation in the values of the
diffusion flux. This phenomenon also contributed to the poor relationship between
labile P and Fe in the sediment which obtained from the October sampling.
Accordingly, we conclude that algal decomposition might be essential for internal
loading of P in this aquatic ecosystem, and that also be the reason for vicious
circle of algal occurrence in the following year in the center of Lake Hongze.
PMID- 27613326
TI - Genotoxic effects of cadmium and influence on fitness components of Lymantria
dispar caterpillars.
AB - The current study extends our previous findings concerning the sensitivity of
Lymantria dispar larvae to cadmium in light of ecotoxicological risk assessment.
Here we report the results of the comet assay performed for the first time on
this species. We examined the chronic effects of two cadmium concentrations (50
and 100 MUg Cd/g dry food) on DNA integrity and haemocyte viability, as well as
on fitness-related traits (larval mass and development duration parameters). All
parameters were assessed individually and then used to calculate the integrated
biomarker response (IBR) index. Egg-masses of L. dispar were collected from two
locations in Serbia - the uncontaminated Homolje mountains and a metal-polluted
area near Bor copper mines, smelter and refinery. Distinctive patterns in the
response of these populations to cadmium exposure were noticed. In haemocytes of
larvae from the pollution-free location both cadmium treatments increased the
level of DNA damage, although in a similar range. Haemocyte viability and larval
mass were reduced, while duration of the fourth instar and total development time
were prolonged in a concentration-dependent manner. Cadmium tolerance was
noticeable in the population from the metal-contaminated site at all
organizational levels. Nevertheless, haemocyte viability in that population was
reduced by the stronger treatment. Haemocyte viability was recognized as a
promising biomarker due to the evident response of both populations to dietary
cadmium. Genotoxicity, fitness-related traits and the IBR index could be used for
biomonitoring of sensitive populations not previously exposed to metals.
PMID- 27613328
TI - Current status and historical variations of DDT-related contaminants in the
sediments of Lake Chaohu in China and their influencing factors.
AB - The temporal-spatial distributions of DDT-related contaminants (DDXs), including
DDT (dichlorodiphenyltrichloroethane), DDE (dichlorodiphenyldichloroethylene) and
DDD (dichlorodiphenyldichloroethane), in the sediments of Lake Chaohu and their
influencing factors were studied. p,p-DDE and p,p-DDD were found to be the two
dominant components of DDXs in both surface and core sediments. The parent DDT
compounds were still detectable in sediment cores after the late 1930s.
Historical usage of technical DDT was identified as the primary source of DDXs in
sediments, as indicated by DDT/(DDD + DDE) ratios of less than one. The residual
levels of DDXs were higher in the surface and core sediments in the western lake
area than in other lake areas, which might be due to the combined inflow effects
of municipal sewage, industrial wastewater and agricultural runoff. The DDX
residues in the sediment cores reached peak values in the late 1970s or early
1980s. There were significant positive relationships between DDX residues in
sediment cores with annual DDT production and with fine particulate sizes (<4.5
MUm). The relationship between the DDXs and TOC in sediment was complex, as
indicated by the significant differences among the surface and core sediments.
The algae-derived organic matter significantly influenced the amount of residue,
composition and distribution of DDXs in the sediments. The DDD/DDE ratios
responded well to the anaerobic conditions in the sediments that were caused by
algal blooms after the late 1970s in the western lake area. This suggests that
the algae-derived organic matter was an important factor and served as a
biomarker of eutrophication and also affected the DDX residues and lifecycle in
the lake ecosystem.
PMID- 27613327
TI - Effects of polycyclic aromatic compounds in fine particulate matter generated
from household coal combustion on response to EGFR mutations in vitro.
AB - Induction of PM2.5-associated lung cancer in response to EGFR-tyrosine kinase
inhibitors (EGFR-TKI) remains unclear. Polycyclic aromatic hydrocarbons (PAHs)
and their polar derivatives (oxygenated PAHs: OPAHs and azaarenes: AZAs) were
characterized in fine particulates (PM2.5) emitted from indoor coal combustion.
Samples were collected in Xuanwei (Yunnan Province), a region in China with a
high rate of lung cancer. Human lung adenocarcinoma cells A549 (with wild-type
EGFR) and HCC827 (with EGFR mutation) were exposed to the PM2.5, followed by
treatment with EGFR-TKI. Two samples showed significant and dose-dependent
reduction in the cell viability in A549. EGFR-TKI further demonstrated
significantly decreased in cell viability in A549 after exposure to the coal
emissions. Chrysene and triphenylene, dibenzo[a,h]anthracene, benzo[ghi]perylene,
azaarenes and oxygenated polycyclic aromatic hydrocarbons (carbonyl-OPAHs) were
all associated with EGFR-TKI-dependent reduced cell viability after 72-h exposure
to the PM2.5. The findings suggest the coal emissions could influence the
response of EGFR-TKI in lung cancer cells in Xuanwei.
PMID- 27613329
TI - Porcine endothelium induces DNA-histone complex formation in human whole blood: a
harmful effect of histone on coagulation and endothelial activation.
AB - BACKGROUND: Neutrophils play a role in xenograft rejection. When neutrophils are
stimulated, they eject the DNA-histone complex into the extracellular space,
called neutrophil extracellular traps (NET). We investigated whether NET
formation actively occurs in the xenograft and contributes to coagulation and
endothelial activation. METHODS: Human whole blood was incubated with porcine
aortic endothelial cells (pEC) from wild-type or alpha1,3-galactosyltransferase
gene-knockout (GTKO) pigs. In the supernatant plasma from human blood, the level
of the DNA-histone complex was measured by ELISA, and thrombin generation was
measured using a calibrated automated thrombogram. Histone-induced tissue factor
and adhesion molecule expression were measured by flow cytometry. RESULTS: pEC
from both wild-type and GTKO pigs significantly induced DNA-histone complex
formation in human whole blood. The DNA-histone complex produced shortened the
thrombin generation time and clotting time. Histone alone dose-dependently
induced tissue factor and adhesion molecule expression in pEC. Aurintricarboxylic
acid pretreatment partially inhibited pEC-induced DNA-histone complex formation.
CONCLUSIONS: DNA-histone complex actively generated upon xenotransplantation is a
novel target to inhibit coagulation and endothelial activation. To prevent tissue
factor and adhesion molecule expression, a strategy to block soluble histone may
be required in xenotransplantation.
PMID- 27613332
TI - Pop-it beads to introduce catalysis of reaction rate and substrate depletion
effects.
AB - A kinesthetic classroom activity was designed to help students understand enzyme
activity and catalysis of reaction rate. Students served the role of enzymes by
manipulating Pop-It Beads as the catalytic event. This activity illuminates the
relationship between reaction rate and reaction progress by allowing students to
experience first-hand the effect of substrate depletion on catalyzed reaction
rate. Preliminary findings based on survey results and exam performance suggest
the activity could prove beneficial to students in the targeted learning
outcomes. Unique to previous kinesthetic approaches that model Michaelis-Menten
kinetics, this activity models the effects of substrate depletion on catalyzed
reaction rate. Therefore, it could prove beneficial for conveying the reasoning
behind the initial rate simplification used in Michaelis-Menten kinetics. (c)
2016 by The International Union of Biochemistry and Molecular Biology, 45(2):179
183, 2017.
PMID- 27613330
TI - In vitro and in vivo antitumor activity of a novel carbonyl ruthenium compound,
the ct-[RuCl(CO)(dppb)(bipy)]PF-6[dppb=1,4-bis(diphenylphosphine)butane and
bipy=2,2'-bipyridine].
AB - This study performed in vitro and in vivo biological assays of the ruthenium (II)
compound ct-[RuCl(CO)(dppb)(bipy)]PF6 (where, dppb=1,4
bis(diphenylphosphine)butane and bipy=2,2'-bipyridine). The cytotoxic activity of
this compound was evaluated against different tumor cell lines (HeLa, human
cervical adenocarcinoma; MCF7, human breast adenocarcinoma; MO59J, human
glioblastoma; HepG2, hepatocellular carcinoma and B16F10, murine melanoma) and
healthy cell line (V79, Chinese hamster lung fibroblasts), by XTT (sodium 2,3'
bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-3,4-tetrazolium
bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) method. A syngeneic murine
melanoma tumor model (B16F10) was used to evaluate its antitumor activity.
Additionally, experiments were performed to assess the interactions with ctDNA
(calf thymus DNA) and BSA (bovine serum albumin). The results showed that ct
[RuCl(CO)(dppb)(bipy)]PF6 was cytotoxic against all tumor cell lines tested.
Furthermore, the compound was more effective against tumor cells compared to the
normal cell line, indicating selectivity, especially in B16F10 cells. Significant
tumor growth reduction was observed in animals treated with the compound compared
to the untreated control. Histopathological analysis of tumor tissue revealed a
significant reduction of mitosis in animals treated with the compound compared to
the untreated control. In the ctDNA and BSA interaction experiments, the compound
in study showed weak interactions with ctDNA and hydrophobic interactions with
BSA. The ruthenium compound investigated showed promising results in in vitro and
in vivo biological assays.
PMID- 27613333
TI - Confabulation and conversation.
AB - Confabulation is sometimes defined - by Berlyne, for example - as a symptom that
is seen only in one neuropsychological condition, amnesia. In this paper I argue
for a somewhat more liberal - and, I contend, more productive - conception of
confabulation, according to which it is seen not only in amnesia but also in
other neuropsychological conditions such as delusion - and, indeed, even in
healthy people. I also argue that it follows from this that in neuropsychological
conditions where confabulations are seen, these are responses to abnormal
experiences brought about by brain damage, but the occurrence of confabulation
itself need not be seen as due to any impairment of cognitive processes due to
the brain damage. It is instead a consequence of a general property of human
cognition that is often referred to as "the drive for causal understanding".
PMID- 27613331
TI - Application of a novel rectal cooling device in hypothermia therapy after
cerebral hypoxia-ischemia in rats.
AB - BACKGROUND: A new rectal cooling device for therapeutic hypothermia (TH) therapy
is designed and is applied in TH treatment of SD rats with ischemic-hypoxic brain
damage. METHODS: Healthy adult SD rats (n = 45) were randomly assigned into four
groups: the healthy control group (n = 5), the ischemia and hypoxia group (n =
10), the rectal TH cooling group (n = 18), and the ice blanket TH cooling group
(n = 11). The rats in the rectal cooling and ice blanket TH groups received 12 h
treatment after hypoxic-ischemic brain damage had been established, while those
in the ischemia and hypoxia group did not. Taking the start of TH as the zero
point, rats were sacrificed after 24 h and the brain and rectum tissues were
sampled for histological analysis. RESULTS: The TH induction time (37.3 +/- 14.7
min) in the rectal cooling group was significantly shorter (F = 4.937, P < 0.05)
than that in the ice blanket cooling group (75.6 +/- 27.2 min). The HE and NISSL
staining results showed that rats in the rectal TH cooling group had
significantly decreased (P < 0.01) positive neurons cell count compared to those
in ischemia and hypoxia group. In addition, TUNEL staining indicated that the
number of apoptotic cells (3.9 +/- 1.8 cells / * 400 field) and the apoptosis
index (4.4 % +/- 1.5) were significantly lower in rectal TH cooling group (P <
0.05) than in ischemia and hypoxia group (23.2 +/- 12.1 cells / * 400 field, 26.6
% +/- 12.1). Also, no rectal frostbite or inflammatory infiltration was observed
in rats in the rectal TH treatment groups. CONCLUSION: Our new cooling device
realized rapid TH induction in SD rats with ischemic-hypoxic brain damage,
inhibited the apoptosis of cells in the hippocampal CAl region, and did not cause
histological damage to the rectal tissues.
PMID- 27613334
TI - Frequency of prepapillary vascular loops in Congolese patients.
AB - PURPOSE: To determine the frequency of prepapillary vascular loops in the
population of Congolese patients. METHODS: We performed a retrospective cross
sectional and descriptive analysis of the data collected between January 2005 and
August 2014 from patients diagnosed with prepapillary vascular loops, in an
outpatient eye clinic, a general ophthalmology practice. RESULTS: Out of 16,016
patients seen during the study period, 24 patients (27 eyes) were diagnosed with
prepapillary vascular loops, for a frequency of 0.15%. The mean age of the
patients with prepapillary vascular loops was 37.8 years+/-14 (SD) (range, 18 to
60 years). Male were more frequently diagnosed with prepapillary vascular loops
than female (62.5% vs 37.5%). Unilateral prepapillary vascular loops were found
in 77.8% and bilateral in 22.2% of eyes. Most of PPLs were estimated to be
arterial (88.9% of eyes) based on clinical observation alone, as fluorescein
angiography was not systematically performed. Ophthalmoscopically, the vessels
appeared as simple (44.6%) or took more serial turns (corkscew or spiral-shaped)
(55.6%). The average length of PPLs was 1.02mm (range 0.6 to 1.5mm) with an
orientation (an axis orientation) in the superior nasal sector (50%), inferior
nasal sector (33%) and superior temporal sector (17%); and a mean axis of 143
degrees relative to the horizontal. Refractive errors were found in 16 eyes
(59.3%) and included simple myopia (4 eyes, 14.8%), myopic astigmatism (8 eyes,
29.6%), hyperopic astigmatism (one eye, 3.7%), hyperopia (3 eyes, 11.1%); One
patient (one eye, 3.7%) with high hyperopia had anisometropia. Primary open angle
glaucoma was found in 5 (18.5%) eyes; vascular tortuosity was seen in two (7.4%)
eyes. No complication such as retinal arterial occlusion, vitreous hemorrhage, or
any other complication was found. CONCLUSION: The frequency of 0.15% found in
this study suggests that although rare, prepapillary vascular loops seem to be a
bit more common in black people than in white and Asian people. An association
between PPLs and refractive errors may be possible.
PMID- 27613335
TI - Longitudinal evaluation of central corneal thickness in congenital glaucoma.
AB - PURPOSE: To assess the central corneal thickness in primary congenital glaucoma
before and after surgical treatment and compare it with a normal population.
METHODS: We conducted a longitudinal analysis of primary congenital glaucoma
patients, in whom we measured central corneal thickness before and after
treatment (Group 1). We compared our results with a normal population (Group 2),
who underwent ophthalmological examination under anesthesia for other reasons.
RESULTS: Mean age (months) in Group 1 (N=23) and Group 2 (N=40) at the time of
the first exam was 5.5 and 9.2 (P=0.004), respectively. Mean central corneal
thickness (microns) in Group 1 was: 663 before treatment and 557 after treatment
(P<0.001). In Group 2, mean central corneal thickness (microns) was 551.
Comparisons show statistical difference between mean values before and after
treatment (P<0.001), but not between post-treatment CCT mean values in Group 1
and mean CCT values in Group 2 (P=0.627). CONCLUSION: In primary congenital
glaucoma, central corneal thickness values show unique peculiarities. They are
higher than normal before treatment (thicker corneas), due to corneal edema
caused by elevated intraocular pressure. After surgical treatment, central
corneal thickness measurements decrease toward the mean values for the normal
population.
PMID- 27613338
TI - Oestradiol effects on neuroendocrine responses induced by water deprivation in
rats.
AB - Water deprivation (WD) induces changes in plasma volume and osmolality, which in
turn activate several responses, including thirst, the activation of the renin
angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These
systems seem to be influenced by oestradiol, as evidenced by the expression of
its receptor in brain areas that control fluid balance. Thus, we investigated the
effects of oestradiol treatment on behavioural and neuroendocrine changes of
ovariectomized rats in response to WD. We observed that in response to WD,
oestradiol treatment attenuated water intake, plasma osmolality and haematocrit
but did not change urinary volume or osmolality. Moreover, oestradiol potentiated
WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang
II) concentrations. Immunohistochemical data showed that oestradiol potentiated
vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and
supraoptic (SON) nuclei but did not induce further changes in Fos expression in
the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic
neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression,
oestradiol increased OT mRNA expression in the SON and PVN under basal conditions
and after WD, but did not induce additional changes in the mRNA expression for
AVP in the SON or PVN. It also did not affect the mRNA expression of RAS
components in the PVN. In conclusion, our results show that oestradiol acts
mainly on the vasopressinergic system in response to WD, potentiating
vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA
expression.
PMID- 27613336
TI - Modeling the impact of growth and leptin deficits on the neuronal regulation of
blood pressure.
AB - The risk of hypertension is increased by intrauterine growth restriction (IUGR)
and preterm birth. In the search for modifiable etiologies for this life
threatening cardiovascular morbidity, a number of pathways have been
investigated, including excessive glucocorticoid exposure, nutritional deficiency
and aberration in sex hormone levels. As a neurotrophic hormone that is
intimately involved in the cardiovascular regulation and whose levels are
influenced by glucocorticoids, nutritional status and sex hormones, leptin has
emerged as a putative etiologic and thus a therapeutic agent. As a product of
maternal and late fetal adipocytes and the placenta, circulating leptin typically
surges late in gestation and declines after delivery until the infant consumes
sufficient leptin-containing breast milk or accrues sufficient leptin-secreting
adipose tissue to reestablish the circulating levels. The leptin deficiency seen
in IUGR infants is a multifactorial manifestation of placental insufficiency,
exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant
suffers from the same cascade of events, including separation from the placenta,
antenatal steroid exposure and persistently underdeveloped adipose depots.
Preterm infants remain leptin deficient beyond term gestation, rendering them
susceptible to neurodevelopmental impairment and subsequent cardiovascular
dysregulation. This pathologic pathway is efficiently modeled by placing neonatal
mice into atypically large litters, thereby recapitulating the perinatal growth
restriction-adult hypertension phenotype. In this model, neonatal leptin
supplementation restores the physiologic leptin surge, attenuates the leptin
triggered sympathetic activation in adulthood and prevents leptin- or stress
evoked hypertension. Further pathway interrogation and clinical translation are
needed to fully test the therapeutic potential of perinatal leptin
supplementation.
PMID- 27613339
TI - Tooth Loss and Decline in Functional Capacity: A Prospective Cohort Study from
the Japan Gerontological Evaluation Study.
AB - OBJECTIVES: To describe associations between tooth loss and changes in higher
level functional capacity. DESIGN: Prospective cohort study. SETTING: Twenty-four
Japanese municipalities between 2010 and 2013. PARTICIPANTS: Functionally
independent community-dwelling persons aged 65 and older (N = 62,333).
MEASUREMENTS: Self-reported number of teeth was used as an exposure variable. The
outcome was changes in higher-level functional capacity measured using the Tokyo
Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), which
consists of three domains: instrumental activities of daily living, intellectual
activity, and social roles. The TMIG-IC score ranges from 0 (lowest function) to
13 (highest function). All covariates were chosen from baseline demographic,
socioeconomic, health behavior, and health variables based upon evidence from
previous studies. Inverse-probability weighting (IPW) with propensity score and
multiple linear regression, estimating nonstandardized coefficients (beta) and
95% confidence intervals (CIs), were used. RESULTS: The baseline response rate
was 65.2%, and the follow-up rate was 70.1%. During the follow-up period,
participants' TMIG-IC score declined by an average of 0.247 points (standard
deviation: 1.446). The results showed a significant dose-response association
between tooth loss and decline in higher-level functional capacity in multiple
linear regression models. IPW models estimated the increment in TMIG-IC score
(beta = 0.170, 95% CI = 0.114 to 0.227) if edentulous participants gained 20 or
more natural teeth. CONCLUSION: Tooth loss is associated with future decline in
higher-level functional capacity. IPW models suggest that treatment for tooth
loss attenuates decline in higher-level functional capacity.
PMID- 27613337
TI - The role of the p53 tumor suppressor in metabolism and diabetes.
AB - In the context of tumor suppression, p53 is an undisputedly critical protein.
Functioning primarily as a transcription factor, p53 helps fend off the
initiation and progression of tumors by inducing cell cycle arrest, senescence or
programmed cell death (apoptosis) in cells at the earliest stages of precancerous
development. Compelling evidence, however, suggests that p53 is involved in other
aspects of human physiology, including metabolism. Indeed, recent studies suggest
that p53 plays a significant role in the development of metabolic diseases,
including diabetes, and further that p53's role in metabolism may also be
consequential to tumor suppression. Here, we present a review of the literature
on the role of p53 in metabolism, diabetes, pancreatic function, glucose
homeostasis and insulin resistance. Additionally, we discuss the emerging role of
genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the
impact of p53 in metabolic disease and diabetes. A better understanding of the
relationship between p53, metabolism and diabetes may one day better inform the
existing and prospective therapeutic strategies to combat this rapidly growing
epidemic.
PMID- 27613340
TI - Screening, Brief Intervention, and Referral to Treatment.
AB - Screening, Brief Intervention, and Referral to Treatment is a quick, effective
technique with which to manage substance use in adolescents and young adults. Use
of a validated measure for detecting substance use and abuse is significantly
more effective than unvalidated tools or provider intuition. There are a variety
of validated tools available to use in the adolescent/young adult population, and
there are opportunities to increase the efficiency and scalability of screening
by using computerized questionnaires. This area continues to evolve rapidly.
PMID- 27613341
TI - Family-Based Treatments for Adolescent Substance Use.
AB - Adolescent substance use is a major risk factor for negative outcomes, including
substance dependence later in life, criminal behavior, school problems, mental
health disorders, injury, and death. This article provides a user-friendly,
clinically focused, and pragmatic review of current and evidence-based family
treatments, including multisystemic therapy, multidimensional family therapy,
functional family therapy, brief strategic family therapy, ecologically based
family therapy, family behavior therapy, culturally informed flexible family
treatment for adolescents, and strengths-oriented family therapy. Outcomes,
treatment parameters, adolescent characteristics, and implementation factors are
reviewed.
PMID- 27613342
TI - Cognitive Behavioral Therapy and Motivational Enhancement Therapy.
AB - Although cognitive behavioral therapy (CBT) is widely recognized as the preferred
treatment of psychiatric disorders, less is known about the application of CBT to
substance use disorders, particularly in adolescence. This article discusses how
CBT conceptualizes substance use and how it is implemented as a treatment of
adolescent substance abuse. The article draws on several manuals for CBT that
implement it as a standalone treatment or in combination with motivational
enhancement therapies. Also reviewed are several studies that examined the
efficacy of CBT. Finally, the implications are discussed. Numerous starting
resources are provided to help a clinician implement CBT.
PMID- 27613343
TI - Advances in Research on Contingency Management for Adolescent Substance Use.
AB - Multiple interventions for treating adolescents with substance use disorders have
demonstrated efficacy, but a majority of teens do not show an enduring positive
response to these treatments. Contingency management (CM)-based strategies
provide a promising alternative, and clinical research focused on the development
and testing of innovative CM models continues to grow. This article provides an
updated review on the progress made in this area. It is important to continue to
search for more effective models, focus on post-treatment maintenance (reduce
relapse), and strive for high levels of integrity and fidelity during
dissemination efforts to optimize outcomes.
PMID- 27613344
TI - Meeting Youth Where They Are: Substance Use Disorder Treatment in Schools.
AB - Providing school-based mental health treatment offers an opportunity to reach a
greater number of affected youth by providing services in the setting where youth
spend the majority of their time. In some contexts, even a single session of
assessment has been linked with significant decreases in substance use; however,
more robust treatments are likely needed to sustain these decreases over time.
Empirically based individual and group treatments designed for delivery in clinic
settings can readily be adapted for implementation in school settings. School
based delivery of substance use services offers an important opportunity to
bridge a significant gap in services.
PMID- 27613345
TI - Continuing Care for Adolescents in Treatment for Substance Use Disorders.
AB - Adolescents who enter treatment for substance use often do not complete the
program and do not connect with continuing care services. Most return to some
level of substance use. Our review found 10 outcome studies of continuing care
treatment. More assertive approaches can increase continuing care initiation
rates and rapid initiation of continuing care makes a difference in reducing
substance use. Continuing care is appropriate for those who complete treatment
and for those who do not. Adaptive treatment designs hold promise for
establishing decision rules as to which adolescents need low-intensity continuing
care services and which need more intensive care.
PMID- 27613347
TI - Cooccurring Psychiatric and Substance Use Disorders.
AB - Research shows that the majority of adolescents with substance use disorders also
have other cooccurring psychiatric disorders, which has been associated with
poorer treatment outcomes. Despite considerable consensus that treatment of
cooccurring disorders should be integrated or concurrent, most such youth do not
receive it. In addition to systemic and economic barriers, few studies have been
conducted that inform evidence-based integrated treatment approaches. This
article provides a review of current research from which empirically derived
principles of integrated treatment can originate and which have informed the
development of at least one evidence-based model of integrated mental health and
substance treatment.
PMID- 27613348
TI - Substance Abuse and Trauma.
AB - There is a strong, bidirectional link between substance abuse and traumatic
experiences. Teens with cooccurring substance use disorders (SUDs) and
posttraumatic stress disorder (PTSD) have significant functional and psychosocial
impairment. Common neurobiological foundations point to the reinforcing cycle of
trauma symptoms, substance withdrawal, and substance use. Treatment of teens with
these issues should include a systemic and integrated approach to both the SUD
and the PTSD.
PMID- 27613346
TI - The Role of Pharmacotherapy in the Treatment of Adolescent Substance Use
Disorders.
AB - Adolescent substance use disorders (SUDs) are a significant public health issue
due to the associated morbidity, mortality, and societal cost. While effective
for some adolescents, psychosocial interventions generally produce small-to
moderate reductions in substance use. Most youth relapse within 12 months of
treatment. One approach to improve outcomes is through adjunctive
pharmacotherapy. Medication assisted treatments have been shown to improve adult
SUD treatment outcomes, and preliminary studies in adolescents suggest that
combining medication with psychosocial interventions may also enhance SUD
outcomes for youth. This article presents a comprehensive review and grading of
the evidence from studies conducted in adolescents with SUDs.
PMID- 27613349
TI - Substance Use Among College Students.
AB - Emerging adulthood has heightened risk for substance use. College students
experience unique challenges, making them prone to use of alcohol, marijuana, and
nonmedical use of prescription drugs. This article reviews rates of college
students' substance use, risk factors, and populations at elevated risk.
Consequences include legal, academic, and mental health problems; engagement in
other risky behaviors; increased rates of injury; and death. Researchers,
clinicians, and university administrators must identify those at greatest risk
and provide prevention and intervention programs. Despite broad evidence
supporting such programs, many students fail to access appropriate treatment.
Future research should elucidate treatment barriers.
PMID- 27613352
TI - Erratum.
PMID- 27613351
TI - Integrated Care for Pediatric Substance Abuse.
AB - Integrated care is a way to improve the prevention, identification, and treatment
of mental health difficulties, including substance abuse, in pediatric care. The
pediatrician's access, expertise in typical development, focus on prevention, and
alignment with patients and families can allow successful screening, early
intervention, and referral to treatment. Successful integrated substance abuse
care for youth is challenged by current reimbursement systems, information
exchange, and provider role adjustment issues, but these are being addressed as
comfort with this care form and resources to support its development grow.
PMID- 27613350
TI - Technology-based Interventions for Preventing and Treating Substance Use Among
Youth.
AB - Preventing or mitigating substance use among youth generally involves 3 different
intervention frameworks: universal prevention, selective prevention, and
treatment. Each of these levels of intervention poses unique therapeutic and
implementation challenges. Technology-based interventions provide solutions to
many of these problems by delivering evidence-based interventions in a consistent
and cost-effective manner. This article summarizes the current state of the
science of technology-based interventions for preventing substance use initiation
and mitigating substance use and associated consequences among youth.
PMID- 27613353
TI - The Changing Landscape of Adolescent Substance Treatment.
PMID- 27613354
TI - Citrulline for urea cycle disorders in Japan.
AB - BACKGROUND: The amino acid l-citrulline is used as a therapeutic agent for urea
cycle disorders (UCD) including ornithine transcarbamylase deficiency (OTCD),
carbamoyl phosphate synthetase I deficiency (CPSD), and N-acetylglutamate
synthase deficiency. There are few reports, however, on the use of l-citrulline
in Japan and little consensus regarding the effects of l-citrulline. METHODS: We
conducted a questionnaire survey of patients undergoing l-citrulline treatment
for a UCD to evaluate the current status of this therapy. The survey included
patient background, details of l-citrulline treatment, clinical examination data,
treatment, frequency of vomiting, and liver transplantation. RESULTS: We
retrospectively investigated 43 questionnaire respondents (OTCD, n = 33; CPSD, n
= 10). The weight of male OTCD patients improved by +0.79 SD, and the ammonia
level decreased by a mean of 44.3 MUmol/L in all patients. The protein intake of
all patients and of male OTCD patients increased by 0.14 g/kg/day and 0.17
g/kg/day, respectively. CONCLUSIONS: l-Citrulline effectively reduced ammonia
level, increased protein intake, and improved weight gain in UCD patients. l
Citrulline should be considered a standard therapy in OTCD and CPSD patients.
PMID- 27613356
TI - Magnetic Resonance Imaging-Transrectal Ultrasound Guided Fusion Biopsy to Detect
Progression in Patients with Existing Lesions on Active Surveillance for Low and
Intermediate Risk Prostate Cancer.
AB - PURPOSE: Active surveillance is an established option for men with low risk
prostate cancer. Multiparametric magnetic resonance imaging with magnetic
resonance imaging-transrectal ultrasound fusion guided biopsy may better identify
patients for active surveillance compared to systematic 12-core biopsy due to
improved risk stratification. To our knowledge the performance of multiparametric
magnetic resonance imaging in following men on active surveillance with visible
lesions is unknown. We evaluated multiparametric magnetic resonance imaging and
magnetic resonance imaging-transrectal ultrasound fusion guided biopsy to monitor
men on active surveillance. MATERIALS AND METHODS: This retrospective review
included men from 2007 to 2015 with prostate cancer on active surveillance in
whom magnetic resonance imaging visible lesions were monitored by multiparametric
magnetic resonance imaging and fusion guided biopsy. Progression was defined by
ISUP (International Society of Urological Pathology) grade group 1 to 2 and ISUP
grade group 2 to 3. Significance was considered at p <=0.05. RESULTS: A total of
166 patients on active surveillance with 2 or more fusion guided biopsies were
included in analysis. Mean followup was 25.5 months. Of the patients 29.5% had
pathological progression. Targeted biopsy alone identified 44.9% of patients who
progressed compared to 30.6% identified by systematic 12-core biopsy alone (p =
0.03). Fusion guided biopsy detected 26% more cases of pathological progression
on surveillance biopsy compared to systematic 12-core biopsy. Progression on
multiparametric magnetic resonance imaging was the sole predictor of pathological
progression at surveillance biopsy (p = 0.013). Multiparametric magnetic
resonance imaging progression in the entire cohort had 81% negative predictive
value, 35% positive predictive value, 77.6% sensitivity and 40.5% specificity in
detecting pathological progression. CONCLUSIONS: Multiparametric magnetic
resonance imaging progression predicts the risk of pathological progression.
Patients with stable multiparametric magnetic resonance imaging findings have a
low rate of progression. Incorporating fusion guided biopsy in active
surveillance nearly doubled our detection of pathological progression compared to
systematic 12-core biopsy.
PMID- 27613357
TI - A randomized double blinded placebo controlled trial of sildenafil for
renoprotection prior to hilar clamping in patients undergoing robotic assisted
laparoscopic partial nephrectomy.
AB - OBJECTIVE: To perform a randomized control trial (RCT) assessing the effect of
phosphodiesterase 5 inhibitor (PDE5i) used prior to hilar clamping during robot
assisted partial nephrectomy (RAPN) for renoprotection. MATERIALS AND METHODS: We
performed an institutional review board approved, placebo controlled, double
blinded RCT evaluating a single 100 mg oral dose of sildenafil immediately prior
to RAPN. Primary end point was accrual, participation and retention of patients
with secondary endpoints assessing post-operative renal functional outcomes and
safety. Exclusion criteria included history of coronary artery disease, solitary
kidney, suspected benign pathology, PDE5i intolerance or pregnant females.
RESULTS: Of 40 eligible consecutive patients undergoing RPN between 9/2013 and
12/2014, 30 (75%) were randomized to treatment and there was 100% participation
and retention. The groups were well matched for all measured comorbidities.
Intraoperative outcomes including warm ischemia time (median 15 vs. 16.5 min, P =
0.29) were similar. Change in eGFR demonstrated similar decrease between
sildenafil versus placebo at 1 day (-8% vs. -10%, P = 0.53), 2 days (-9% vs. -9%,
P = 0.77), and 1 month (-4% vs. -6%, P = 0.31) following RAPN. Intermediate
follow up (median 183 days) demonstrated similar results (-8% vs. -1%, P = 0.16)
between the two cohorts. Safety profiles were similar between the two cohorts
without any adverse reactions to the sildenafil. CONCLUSIONS: Successful
retention of patients was achieved in this RCT. The secondary outcome of
renoprotection was not identified. J. Surg. Oncol. 2016;114:785-788. (c) 2016
2016 Wiley Periodicals, Inc.
PMID- 27613358
TI - Maternal chewing during prenatal stress ameliorates stress-induced
hypomyelination, synaptic alterations, and learning impairment in mouse
offspring.
AB - Maternal chewing during prenatal stress attenuates both the development of stress
induced learning deficits and decreased cell proliferation in mouse hippocampal
dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic
structure is a key mediator of neuronal communication. We investigated whether
maternal chewing during prenatal stress ameliorates stress-induced alterations of
hippocampal myelin and synapses, and impaired development of spatial memory in
adult offspring. Pregnant mice were divided into control, stress, and
stress/chewing groups. Stress was induced by placing mice in a ventilated
restraint tube, and was initiated on day 12 of pregnancy and continued until
delivery. Mice in the stress/chewing group were given a wooden stick to chew
during restraint. In 1-month-old pups, spatial memory was assessed in the Morris
water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by
immunohistochemistry and electron microscopy. Prenatal stress led to impaired
learning ability, and decreased immunoreactivity of myelin basic protein (MBP)
and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1
in adult offspring. Numerous myelin sheath abnormalities were observed. The G
ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was
increased and postsynaptic density length was decreased in the hippocampal CA1
region. Maternal chewing during stress attenuated the prenatal stress-induced
impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity,
increased G-ratios, and decreased postsynaptic-density length in the hippocampal
CA1 region. These findings suggest that chewing during prenatal stress in dams
could be an effective coping strategy to prevent hippocampal behavioral and
morphologic impairments in their offspring.
PMID- 27613359
TI - Favorable neurological outcomes by early epinephrine administration within 19
minutes after EMS call for out-of-hospital cardiac arrest patients.
AB - OBJECTIVE: To evaluate the time-independent effect of the early administration of
epinephrine (EPI) on favorable neurological outcome (as CPC [cerebral performance
category] 1-2) at 1 month in patients with out-of-hospital cardiac arrest.
MATERIALS AND METHODS: A total of 119 639 witnessed cardiac arrest patients from
2008 to 2012 were eligible for this nationwide, prospective, population-based
observational study. Patients were divided into EPI group (n = 20 420) and non
EPI group (n = 99 219). To determine the time-dependent effects of EPI, EPI
administered patients were divided into 4 groups as follows: early EPI (5-18
min), intermediate EPI (19-23 min), late EPI (24-29 min), and very late EPI (30
62 min), respectively. Multiple logistic regression analyses and adjusted odds
ratios (AORs) were determined for CPC 1-2 at 1 month (primary outcome) and field
return of spontaneous circulation (as secondary outcome) among the groups.
RESULTS: The EPI and non-EPI group had identical background, but EPI group shows
higher incidence public access defibrillation and emergency medical technician
defibrillation delivered than the non-EPI group. The differences were clinically
negligible. Higher return of spontaneous circulation rate (18.0%) and lower CPC 1
2 (2.9%) shown in the EPI group than in the non-EPI group (9.4% and 5.2%). In the
time dependent analysis, CPC 1 to 2 was greatest in the early EPI group (AOR,
2.49; 95% confidence interval [CI], 1.90-3.27), followed by the intermediate EPI
group (AOR, 1.53; 95% CI, 1.14-2.05) then the late EPI group (AOR, 0.71; 95% CI,
0.47-1.08) as reference. CONCLUSION: Early EPI administration within 19 minutes
after emergency medical service call independently improved the neurological
outcome compared with late EPI (24-29 minutes) administration in patients with
out-of-hospital cardiac arrest.
PMID- 27613360
TI - Presenting hemodynamic phenotypes in ED patients with confirmed sepsis.
AB - OBJECTIVES: To derive distinct clusters of septic emergency department (ED)
patients based on their presenting noninvasive hemodynamic (HD) measurements and
to determine if any clinical parameters could identify these groups. METHODS:
Prospective, observational, convenience study of individuals with confirmed
systemic infection. Presenting, pretreatment noninvasive HD parameters were
compiled using Nexfin (Bmeye/Edwards LifeSciences) from 127 cases. Based on
normalized parameters, k-means clustering was performed to identify a set of
variables providing the greatest level of intercluster discrimination and
intracluster cohesion. RESULTS: Our best HD clustering model used 2 parameters:
the cardiac index (CI [L/min per square meter]) and systemic vascular resistance
index (SVRI [dynes.s/cm5 per square meter]). Using this model, 3 different
patient clusters were identified. Cluster 1 had high CI with normal SVRI (CI,
4.03 +/- 0.61; SVRI, 1655.20 +/- 348.08); cluster 2 low CI with increased
vascular tone (CI, 2.50 +/- 0.50; SVRI, 2600.83 +/- 576.81); and cluster 3 very
low CI with markedly elevated SVRI (CI, 1.37 +/- 0.81; SVRI, 5951.49 +/-
1480.16). Cluster 1 patients had the lowest 30-day overall mortality. Among
clinically relevant variables available during the initial patient evaluation in
the ED age, heart rate and temperature were significantly different across the 3
clusters. CONCLUSIONS: Emergency department patients with confirmed sepsis had 3
distinct cluster groupings based on their presenting noninvasively derived CI and
SVRI. Further clinical studies evaluating the effect of early cluster-specific
therapeutic interventions are needed to determine if there are outcome benefits
of ED HD phenotyping in these patients.
PMID- 27613361
TI - Predictors of Mortality in Sepsis : the authors respond.
PMID- 27613362
TI - Ultrasound-guided superficial cervical plexus blockade for acute spasmodic
torticollis in the ED.
PMID- 27613364
TI - ED neuro-ultrasonography and the mental foramen: Practice makes perfect.
PMID- 27613363
TI - Variation in advanced imaging for pediatric patients with abdominal pain
discharged from the ED.
AB - BACKGROUND: Pediatric abdominal pain visits to emergency departments (ED) are
common. The objectives of this study are to assess variation in imaging
(ultrasound +/-computed tomography [CT]) and factors associated with isolated CT
use. METHODS: This was a retrospective cohort study of ED visits for pediatric
abdominal pain resulting in discharge from 16 regional EDs from 2007 to 2013.
Primary outcome was ultrasound or CT imaging. Secondary outcome was isolated CT
use. We used multivariable logistic regression to evaluate patient- and hospital
level covariates associated with imaging. RESULTS: Of the 21 152 visits, imaging
was performed in 29.7%, and isolated CT in 13.4% of visits. In multivariable
analysis, black patients (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.4
0.5) and Medicaid (OR, 0.6; 95% CI, 0.5-0.7) had lower odds of advanced imaging
compared with white patients and private insurance, respectively. General EDs
were less likely to perform imaging (OR, 0.6; 95% CI, 0.5-0.7) compared with the
pediatric ED; however, for visits with imaging, 3.5% of visits to the pediatric
ED compared with 76% of those to general EDs included an isolated CT (P<.001).
Low pediatric volume (OR, 1.8; 95% CI, 1.5-2.2) and rural (OR,1.8; 95% CI, 1.3
2.5) EDs had higher odds of isolated CT use, compared with higher pediatric
volumes and nonrural EDs, respectively. CONCLUSION: There are racial and
insurance disparities in imaging for pediatric abdominal pain. General EDs are
less likely than pediatric EDs to use imaging, but more likely to use isolated
CT. Strategies are needed to minimize disparities and improve the use of
"ultrasound first."
PMID- 27613366
TI - Food allergy: Past, present and future.
AB - Hippocrates is often credited with first recognizing that food could be
responsible for adverse symptoms and even death in some individuals, but it was
not until the seminal observations by Prausnitz that the investigation of food
allergy was viewed on a more scientific basis. In the first half of the 20th
century, there were periodic reports in the medical literature describing various
food allergic reactions. In the mid- to late- 1970's, the studies of Charles May
and colleagues began to penetrate the medical world's skepticism about the
relevance of food allergy and how to diagnose it, since standard skin testing was
known to correlate poorly with clinical symptoms. With May's introduction of the
double-blind placebo-controlled oral food challenge, the study of food allergy
became evidence-based and exponential strides have been made over the past four
decades in the study of basic immunopathogenic mechanisms and natural history,
and the diagnosis and management of food allergies. Today IgE- and non-IgE
mediated food allergic disorders are well characterized and efforts to treat
these allergies by various immunotherapeutic strategies are well under way.
PMID- 27613365
TI - Interactions of linezolid and second-line anti-tuberculosis agents against
multidrug-resistant Mycobacterium tuberculosis in vitro and in vivo.
AB - OBJECTIVES: The objectives of this study were to evaluate the interactions
between linezolid (LZD) and second-line anti-tuberculosis (TB) agents in
susceptible and multidrug-resistant (MDR) TB in vitro, and to validate the in
vitro results in a murine TB model. METHODS: The minimum inhibitory
concentrations of LZD and seven second-line anti-TB drugs against H37Rv and three
multidrug-resistant clinical isolates were determined by Alamar Blue assay, and
the interaction patterns of LZD and the seven second-line anti-TB agents against
the four isolates were studied using a dynamic checkerboard method. The
activities of these combinations against Mycobacterium tuberculosis were
evaluated in a murine model of TB. RESULTS: The combination of LZD + capreomycin
exhibited partial synergism for three of four isolates, LZD + para-aminosalicylic
acid exhibited partial synergism for two of four isolates, and LZD + levofloxacin
and LZD + amikacin exhibited partial synergism for one of four isolates; all
other combinations showed indifference or an additive effect in vitro. The
activities of six combinations and the standard regimen rifampicin + isoniazid +
pyrazinamide were investigated in a murine model of TB (infection with H37Rv).
Significant reductions in colony-forming units (CFU) were found in LZD +
capreomycin and LZD + clofazimine groups when the CFU in the lungs on day 0 (the
day of beginning treatment) was compared with the CFU in the lungs after 2 months
of treatment. CONCLUSIONS: These combinations of LZD and second-line anti-TB
drugs were all active against MDR-TB with indifference or an additive effect,
except LZD + capreomycin, which showed partial synergy.
PMID- 27613367
TI - Large artery stiffness is associated with gamma-glutamyltransferase in young,
healthy adults: The African-PREDICT study.
AB - Increased arterial stiffness is linked to cardiovascular disease development,
particularly in black populations. Since detrimental health behaviors in young
adults may affect arterial stiffness, we determined whether arterial stiffness
associates with specific health behaviors, and whether it is more pronounced in
young healthy black compared to white adults. We included 373 participants (49%
black, 42% men) aged 20-30 years. Mean arterial pressure was higher for blacks
than whites (P < .001), but carotid-femoral pulse wave velocity was similar (6.37
vs. 6.36 m/s; P = .89) after adjustment for mean arterial pressure. The black
group had higher gamma-glutamyltransferase (GGT) (P < .001), cotinine, reactive
oxygen species, interleukin-6, and monocyte-chemoattractant protein-1 (all P <=
.017). Pulse wave velocity related positively and independently to GGT in both
groups before and after multiple adjustments (both beta = 0.15; P <= .049).
Blacks had an unfavorable vascular profile and higher GGT, possibly indicating a
higher vulnerability to cardiovascular disease development, including changes in
arterial stiffness. However, this observation needs confirmation.
PMID- 27613368
TI - Can socio-economic differences explain low expectation of health services among
HIV patients compared to non-HIV counterparts?
AB - BACKGROUND: The health service of China has encountered significant challenges
due to inequalities in socio-economic determinants of health. HIV patients are
known to suffer from social stigma, and may receive inadequate responsiveness
from health providers. Before assessing the responsiveness they receive, it is
important to know their expectations. We aimed to compare levels of expectation
towards the healthcare service among HIV and non-HIV patients with adjustment for
socio-economic factors. METHODS: A cross-sectional study was conducted during
January and February, 2015 among two consecutive groups of HIV positive and non
HIV patients in two hospitals in Kunming, China. Patients' expectation towards
eight domains of health system responsiveness was measured using 40 vignettes;
five per domain. Each vignette was ranked from 1 "very good" to 5 "very bad", and
the responses were summed to obtain a total score for each domain. Differences in
total scores were compared between the two groups and adjusted for other factors
using multiple linear regression. RESULTS: The three domains with the highest
scores, reflecting high expectation, were prompt attention, basic amenities and
choice. Adjusted for other factors, HIV patients had significantly lower levels
of expectation in all domains compared to the non-HIV group. Age was associated
with the basic amenities domain, with young adults having higher expectations
than other age groups. Minority ethnic groups had lower expectation towards
dignity, prompt attention and autonomy domains compared to Han ethnicity. Those
who lived in a home with 2-4 family members had higher expectations towards
confidentiality than those who lived alone. CONCLUSION: Patients with HIV have
significantly lower levels of expectations even after adjusting for socio
economic factors. Assessment of health system responsiveness based on their
judgments above may give biased results toward favorable service quality.
PMID- 27613369
TI - Testing the validity of the proposed ICD-11 PTSD and complex PTSD criteria using
a sample from Northern Uganda.
AB - BACKGROUND: The International Classification of Diseases (ICD-11) is currently
under development with proposed changes recommended for the posttraumatic stress
disorder (PTSD) diagnosis and the inclusion of a separate complex PTSD (CPTSD)
disorder. Empirical studies support the distinction between PTSD and CPTSD;
however, less research has focused on non-western populations. OBJECTIVE: The aim
of this study was to investigate whether distinct PTSD and CPTSD symptom classes
emerged and to identify potential risk factors and the severity of impairment
associated with resultant classes. METHODS: A latent class analysis (LCA) and
related analyses were conducted on 314 young adults from Northern Uganda. Fifty
one percent were female and participants were aged between 18 and 25 years. Forty
percent of the participants were former child soldiers (n=124) while the
remaining participants were civilians (n=190). RESULTS: The LCA revealed three
classes: a CPTSD class (40.2%), a PTSD class (43.8%), and a low symptom class
(16%). Child soldier status was a significant predictor of both CPTSD and PTSD
classes (OR=5.96 and 2.82, respectively). Classes differed significantly on
measures of anxiety/depression, conduct problems, somatic complaints, and war
experiences. CONCLUSIONS: To conclude, this study provides preliminary support
for the proposed distinction between PTSD and CPTSD in a young adult sample from
Northern Uganda. However, future studies are needed using larger samples to test
alternative models before firm conclusions can be made.
PMID- 27613370
TI - Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in
patients with gastrointestinal cancer: a pilot prospective cohort study.
AB - BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the
treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN)
in the upper and lower extremities is the major adverse side effect and
represents the main dose-limiting factor of this drug. The aim of this single-arm
study was to evaluate the feasibility and effects of laser acupuncture (LA) in
the treatment of OIPN in patients with advanced gastrointestinal cancers.
METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric
cancers), who had been treated with oxaliplatin-based chemotherapies, were
recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9,
LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12
sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy
induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity
scale (OSNS), quantitative touch-detection threshold (using von Frey filaments),
and cold-triggered pain withdrawal latency (using the cold-water immersion test)
were measured before and after completion of the 12 treatment sessions. RESULTS:
PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold
trigger pain withdrawal latency all improved significantly after LA in the cancer
patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced
cold and mechanical allodynia and also decreased the incidence and severity of
neurotoxicity symptoms in the patients' upper and lower extremities and impact on
their daily activities (all p<0.05). CONCLUSIONS: Following treatment with LA,
neurotoxicity symptoms were significantly improved in cancer patients with OIPN.
Further randomised controlled trials are needed to evaluate the role of LA as a
therapeutic option in the management of OIPN.
PMID- 27613371
TI - A new comprehensive 12-segment approach to right ventricular systolic and
diastolic functions by 2D speckle tracking echocardiography in healthy
individuals.
AB - BACKGROUND: 2D speckle tracking echocardiography (2DSTE) was proved to be
accurate for the assessment of the RV function. However, normal values for RV
strain refer mostly to 3- or 6-segment models, excluding the contribution of
other RV walls to RV function. We analyze RV function by 2DSTE in a normal
population, using parasternal two-(2C) and apical four-chamber (4C) RV views, and
creating a new 12-segment model for a potential better definition of RV function.
METHODS: We prospectively evaluated 100 normals using 2DE and STE. We assessed
the RV systolic function from regional strain (basal, mid, and apical), and at
the level of each wall: lateral (LS), septal (SS), inferior (IS), and anterior
(AS), and also global strain for 4C (4CGS), and 2C (2CGS). Global systolic strain
rate (SRs) was measured from 2C and 4C views. Diastolic function was assessed
from early (SRe) and late global strain rate (SRl), for both views. RESULTS: A
total of 70 healthy individuals (48+/-15 years, 34 men) were suitable for
concomitant 4C and 2CRV analysis. Feasibility of the STE analysis was 87.8%. We
found significantly lower SS by comparison with LS, AS, and IS (P<.001). All S/SR
parameters (GS, SRs, and SRe) were higher in 2C view than in 4C view (P<.001).
All systolic S/SR parameters did not change with age. The early diastolic SR
decreased, while the late diastolic SR increased with age. CONCLUSION: Our 12
segment RV strain model is feasible. Moreover, 2DSTE analysis using 2C and 4C
views of the RV does not provide similar information. Rather, they offer
complementary data. This might be of particularly clinical interest in diseases
with regional RV dysfunction.
PMID- 27613372
TI - Prognostic Importance of C-KIT Mutations in Core Binding Factor Acute Myeloid
Leukemia: A Systematic Review.
AB - OBJECTIVE/BACKGROUND: Acute myeloid leukemia (AML) is defined as leukemic blast
reproduction in bone marrow. Chromosomal abnormalities form different subgroups
with joint clinical specifications and results. t(8;21)(q22;q22) and
inv(16)(p13;q22) form core binding factor-AML (CBF-AML). c-kit mutation
activation occurs in 12.8-46.1% of adults with CBF leukemia. These mutations
occur in 20-25% of t(8;21) and 30% of inv(16) cases. METHODS: In this systematic
review, we searched different databases, including PubMed, Scopus, and Embase.
Selected articles were measured based on the inclusion criteria of this study and
initially compared in terms of titles or abstracts. Finally, articles relevant to
the subject of this review were retrieved in full text. Twenty-two articles
matched the inclusion criteria and were selected for this review. RESULTS: In
this study, c-kit mutations were associated with poor prognosis in AML patients
with t(8;21) and inv(16). In addition, these mutations had better prognostic
effects on AML patients with inv(16) compared with those with t(8;21).
CONCLUSION: According to the results of this study, c-kit mutations have intense,
harmful effects on the relapse and white blood cell increase in CBF-AML adults.
However, these mutations have no significant prognostic effects on patients.
PMID- 27613373
TI - Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by
definitive surgery in patients with operable rectal cancer.
AB - BACKGROUND: Achieving a high rate of complete pathological response with pre
operative chemoradiotherapy in rectal cancer is an unmet need. We evaluated the
efficacy and toxicity of the combination of cetuximab, capecitabine and radiation
therapy in the pre-operative setting of localized rectal cancer. PATIENTS AND
METHODS: Patients with clinically staged T3, T4 or nodepositive rectal cancer
were treated with concurrent capecitabine and radiotherapy with weekly cetuximab
starting one week before the start of radiation. This was followed by total
mesorectal excision within 6-8 weeks. All patients achieving R0 resection
received adjuvant capecitabine for 6 cycles. RESULTS: Fifteen patients were
treated and all underwent surgery. Sphincter preservation was achieved in 11
patients (73.3%) and pathological complete response in two. With a median follow
up of 48 months (range 8.4-57.5), 12 patients were relapse-free and 14 were alive
with 4-year relapse free survival of 80%. Overall survival was 93%. Significant
grade 3 and 4 toxicity was mainly cetuximab-induced skin reactions (33%),
radiation-induced skin toxicity (13%) and diarrhea (20%). CONCLUSIONS: Adding
cetuximab to pre-operative concurrent capecitabine and radiotherapy provides
modest efficacy with manageable toxicity.
PMID- 27613374
TI - Expanding rural access to mental health care through online postgraduate nurse
practitioner education.
AB - BACKGROUND AND PURPOSE: Workforce shortages in mental health care are especially
relevant to rural communities. People often turn to their primary care providers
for mental healthcare services, yet primary care providers indicate that more
education is needed to fill this role. Rural primary care nurse practitioners
(NPs) are ideal candidates for educational enhancement. Online programs allow NPs
to continue living and working in their communities while developing the
competencies to provide comprehensive and integrated mental healthcare services.
This article presents a review of current online postgraduate psychiatric mental
health NP (PMHNP) options. METHODS: Website descriptions of online PMHNP programs
were located using keywords: PMHNP or psychiatric nurse practitioner,
postgraduate or post-master's, and distance or online. CONCLUSIONS: Across the
United States, 15 online postgraduate certificate programs were located that are
designed for primary care NPs seeking additional PMHNP specialization.
IMPLICATIONS FOR PRACTICE: For rural primary care NPs who are ready, willing, and
able, a postgraduate PMHNP specialty certificate can be obtained online in as few
as three to four semesters. The expected outcome is a cadre of dually
credentialed NPs capable of functioning in an integrated role and of increasing
rural access to comprehensive mental healthcare services.
PMID- 27613376
TI - A Material History of Electroshock Therapy : Electroshock Technology in Europe
until 1945.
AB - The article considers the history of electroshock therapy as a history of medical
technology, professional cooperation and business competition. A variation of a
history from below is intended; though not from the patients' perspective
(Porter, Theory Soc 14:175-198, 1985), but with a focus on electrodes, circuitry
and patents. Such a 'material history' of electroshock therapy reveals that the
technical make-up of electroshock devices and what they were used for was
relative to the changing interests of physicians, industrial companies and mental
health politics; it makes an intriguing case for the Social Construction of
Technology theory (Bijker et al., The social construction of technological
systems: new directions in the sociology and history of technology. MIT Press,
Cambridge, MA, 1987).
PMID- 27613375
TI - Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin
model (EpiDermTM).
AB - BACKGROUND: The rapid production and incorporation of engineered nanomaterials
into consumer products alongside research suggesting nanomaterials can cause cell
death and DNA damage (genotoxicity) makes in vitro assays desirable for
nanosafety screening. However, conflicting outcomes are often observed when in
vitro and in vivo study results are compared, suggesting more physiologically
representative in vitro models are required to minimise reliance on animal
testing. METHOD: BASF Levasil(r) silica nanoparticles (16 and 85 nm) were used to
adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials
administered topically or into the growth medium. 3D dose-responses were compared
to a 2D micronucleus assay using monocultured human B cells (TK6) after
standardising dose between 2D / 3D assays by total nanoparticle mass to cell
number. Cryogenic vitrification, scanning electron microscopy and dynamic light
scattering techniques were applied to characterise in-medium and air-liquid
interface exposures. Advanced transmission electron microscopy imaging modes
(high angle annular dark field) and X-ray spectrometry were used to define
nanoparticle penetration / cellular uptake in the intact 3D models and 2D
monocultured cells. RESULTS: For all 2D exposures, significant (p < 0.002)
increases in genotoxicity were observed (>=100 MUg/mL) alongside cell viability
decreases (p < 0.015) at doses >=200 MUg/mL (16 nm-SiO2) and >=100 MUg/mL (85 nm
SiO2). In contrast, 2D-equivalent exposures to the 3D models (<=300 MUg/mL)
caused no significant DNA damage or impact on cell viability. Further increasing
dose to the 3D models led to probable air-liquid interface suffocation.
Nanoparticle penetration / cell uptake analysis revealed no exposure to the live
cells of the 3D model occurred due to the protective nature of the skin model's
3D cellular microarchitecture (topical exposures) and confounding barrier effects
of the collagen cell attachment layer (in-medium exposures). 2D monocultured
cells meanwhile showed extensive internalisation of both silica particles causing
(geno)toxicity. CONCLUSIONS: The results establish the importance of tissue
microarchitecture in defining nanomaterial exposure, and suggest 3D in vitro
models could play a role in bridging the gap between in vitro and in vivo
outcomes in nanotoxicology. Robust exposure characterisation and uptake
assessment methods (as demonstrated) are essential to interpret
nano(geno)toxicity studies successfully.
PMID- 27613377
TI - Peripheral primitive neuroectodermal tumors of the spine: a case report and
review of the literature.
AB - BACKGROUND: Peripheral primitive neuroectodermal tumors are extremely rare tumors
in the spine; only 18 cases of extra-dural peripheral primitive neuroectodermal
tumor cervical region have been reported. The aim of this report is to highlight
the challenges in diagnosis and management of this condition. CASE PRESENTATION:
We present a case of 5-year-old Moroccan boy, who presented with torticollis for
1 month. Computed tomography scan and Magnetic resonance imaging of the cervical
spine revealed an extradural, dumbbell-shaped mass with extra-spinal extension at
the left C1-C6 level. Multiple biopsy specimens were obtained. Histological
examination revealed a highly cellular neoplasm composed of diffuse sheets of
tumor cells having monomorphic, round to oval, finely vesicular nuclei.
Immunohistochemical findings confirmed the diagnosis of intraspinal peripheral
primitive neuroectodermal tumor. CONCLUSION: After this illustrative case, we
review the literature on clinicopathological and therapeutic aspects. In
practice, it is important to consider the diagnosis of peripheral primitive
neuroectodermal tumor in children and adolescents with an apparent soft-tissue
mass located in the spine.
PMID- 27613378
TI - The effectiveness of clinical networks in improving quality of care and patient
outcomes: a systematic review of quantitative and qualitative studies.
AB - BACKGROUND: Reorganisation of healthcare services into networks of clinical
experts is increasing as a strategy to promote the uptake of evidence based
practice and to improve patient care. This is reflected in significant financial
investment in clinical networks. However, there is still some question as to
whether clinical networks are effective vehicles for quality improvement. The aim
of this systematic review was to ascertain the effectiveness of clinical networks
and identify how successful networks improve quality of care and patient
outcomes. METHODS: A systematic search was undertaken in accordance with the
PRISMA approach in Medline, Embase, CINAHL and PubMed for relevant papers between
1 January 1996 and 30 September 2014. Established protocols were used separately
to examine and assess the evidence from quantitative and qualitative primary
studies and then integrate findings. RESULTS: A total of 22 eligible studies (9
quantitative; 13 qualitative) were included. Of the quantitative studies, seven
focused on improving quality of care and two focused on improving patient
outcomes. Quantitative studies were limited by a lack of rigorous experimental
design. The evidence indicates that clinical networks can be effective vehicles
for quality improvement in service delivery and patient outcomes across a range
of clinical disciplines. However, there was variability in the networks' ability
to make meaningful network- or system-wide change in more complex processes such
as those requiring intensive professional education or more comprehensive
redesign of care pathways. Findings from qualitative studies indicated networks
that had a positive impact on quality of care and patients outcomes were those
that had adequate resources, credible leadership and efficient management coupled
with effective communication strategies and collaborative trusting relationships.
CONCLUSIONS: There is evidence that clinical networks can improve the delivery of
healthcare though there are few high quality quantitative studies of their
effectiveness. Our findings can provide policymakers with some insight into how
to successfully plan and implement clinical networks by ensuring strong clinical
leadership, an inclusive organisational culture, adequate resourcing and
localised decision-making authority.
PMID- 27613379
TI - Complementarity of SOMAscan to LC-MS/MS and RNA-seq for quantitative profiling of
human embryonic and mesenchymal stem cells.
AB - : Dynamic range limitations are challenging to proteomics, particularly in
clinical samples. Affinity proteomics partially overcomes this, yet suffers from
dependence on reagent quality. SOMAscan, an aptamer-based platform for over 1000
proteins, avoids that issue using nucleic acid binders. Targets include low
expressed proteins not easily accessible by other approaches. Here we report on
the potential of SOMAscan for the study of differently sourced mesenchymal stem
cells (MSC) in comparison to LC-MS/MS and RNA sequencing. While targeting fewer
analytes, SOMAscan displays high precision and dynamic range coverage, allowing
quantification of proteins not measured by the other platforms. Expression
between cell types (ESC and MSC) was compared across techniques and uncovered the
expected large differences. Sourcing was investigated by comparing subtypes: bone
marrow-derived, standard in clinical studies, and ESC-derived MSC, thought to
hold similar potential but devoid of inter-donor variability and proliferating
faster in vitro. We confirmed subtype-equivalency, as well as vesicle and
extracellular matrix related processes in MSC. In contrast, the proliferative
nature of ESC was captured less by SOMAscan, where nuclear proteins are
underrepresented. The complementary of SOMAscan allowed the comprehensive
exploration of CD markers and signaling molecules, not readily accessible
otherwise and offering unprecedented potential in subtype characterization.
SIGNIFICANCE: Mesenchymal stem cells (MSC) represent promising stem cell-derived
therapeutics as indicated by their application in >500 clinical trials currently
registered with the NIH. Tissue-derived MSC require invasive harvesting and imply
donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may
provide an alternative and thus warrant thorough characterization. In
continuation of our previous study where we compared in depth embryonic stem
cells (ESC) and MSC from two sources (bone marrow and ESC-derived), we included
the aptamer-based SOMAscan assay, complementing LC-MS/MS and RNA-seq data.
Furthermore, SOMAscan, a targeted proteomics platform developed for analyzing
clinical samples, has been benchmarked against established analytical platforms
(LC-MS/MS and RNA-seq) using stem cell comparisons as a model.
PMID- 27613380
TI - Nocardiopsis rhizosphaerae sp. nov., isolated from rhizosphere soil of
Halocnermum strobilaceum (Pall.) Bieb.
AB - An alkalitolerant actinomycete strain, designated EGI 80674T, was isolated from a
rhizosphere soil of Halocnermumstrobilaceum (Pall.) Bieb in Xinjiang, north-west
China and subjected to a taxonomic characterization using a polyphasic approach.
Strain EGI 80674T formed white aerial hyphae with long spore chains. Whole-cell
hydrolysates of the isolate contained meso-diaminopimelic acid as the diagnostic
diamino acid with no diagnostic sugars. The major fatty acids identified were iso
C16 : 0, anteiso-C17 : 0 and 10-methyl-C18 : 0TBSA. The predominant menaquinones
detected were MK-10(H8) and MK-10(H6). The G+C content of the genomic DNA of
strain EGI 80674T was 70.9 mol%. Strain EGI 80674T showed the highest 16S rRNA
gene sequence similarity (97.24 %) to Nocardiopsis nikkonensis NBRC 102170T. The
DNA-DNA relatedness value of strain EGI 80674T and N. nikkonensis NBRC 102170T
was 18.4+/-1.3 %. Phenotypical, chemotaxonomic and phylogenetic characteristics
and DNA-DNA hybridization data suggest that strain EGI 80674T represents a novel
species of the genus Nocardiopsis, for which the name Nocardiopsis rhizosphaerae
sp. nov. is proposed. The type strain is EGI 80674T (=CGMCC 4.7228T=KCTC 39673T).
PMID- 27613382
TI - Nutraceuticals: A paradigm of proactive medicine.
AB - Nutraceuticals define a new category which shades the frontier between drugs and
food. As per its definition, a nutraceutical is "a food or part of a food that
provides benefits health in addition to its nutritional content". Active
substances either way extracted from plants (phytocomplexes) or of animal origin,
when extracted, concentrated and administered in a suitable pharmaceutical form,
can create a very promising toolbox useful to prevent and/or support the therapy
of some pathologic conditions given their proven clinical efficacy. It is
worldwide recognized that diet and lifestyle are essential to promote and
maintain well-being and nice-being condition, other than help to prevent diseases
possible onset. Both non-correct dietary habits and lifestyle can in fact
determine pathological conditions. The metabolic syndrome, a worldwide epidemic
threat, can be named an outstanding example. This syndrome is characterized by a
cascade of cardio metabolic risk factors which include obesity, insulin
resistance, hypertension, and dyslipidemia. Prevention is the key strategy for an
effective proactive medicine, in which efforts are addressed to prevention and,
consequently, to lower the risk connected to some lifestyle related diseases
reducing, at the same time, any National Health Systems cost needed to guarantee
the proper therapeutic approach based on pharmaceuticals. Nutraceuticals use in
prevention is a proactive reverse approach tool to pre-clinical health
conditions. They can be effectively used, by including in the daily diet, in an
area which shades in the range "beyond the diet, before drugs", since they
combine both nutritional and beneficial healthy properties of food extracts with
the healing properties of natural active compounds.
PMID- 27613381
TI - Genome-wide characterization and expression analysis of MYB transcription factors
in Gossypium hirsutum.
AB - BACKGROUND: MYB family proteins are one of the most abundant transcription
factors in the cotton plant and play diverse roles in cotton growth and
evolution. Previously, few studies have been conducted in upland cotton,
Gossypium hirsutum. The recent release of the G. hirsutum genome sequence
provides a great opportunity to identify and characterize the entire upland
cotton MYB protein family. RESULTS: In this study, we undertook a comprehensive
genome-wide characterization and expression analysis of the MYB transcription
factor family during cotton fiber development. A total of 524 non-redundant
cotton MYB genes, among 1986 MYB and MYB-related putative proteins, were
identified and classified into four subfamilies including 1R-MYB, 2R-MYB, 3R-MYB,
and 4R-MYB. Based on phylogenetic tree analysis, MYB transcription factors were
divided into 16 subgroups. The results showed that the majority (69.1 %) of
GhMYBs genes belong to the 2R-MYB subfamily in upland cotton. CONCLUSION: Our
comparative genomics analysis has provided novel insights into the roles of MYB
transcription factors in cotton fiber development. These results provide the
basis for a greater understanding of MYB regulatory networks and to develop new
approaches to improve cotton fiber development.
PMID- 27613383
TI - Simvastatin-loaded nanostructured lipid carriers attenuate the atherogenic risk
of erythrocytes in hyperlipidemic rats.
AB - This study aimed to investigate the effect of simvastatin (SV) loaded
nanostructured lipid carriers (SV loaded NLCs) on atherogenic index (AI),
erythrocytes membrane lipid and antioxidant/pro-oxidant status in hyperlipidemic
rats. SV loaded NLCs were successfully prepared with desired nano-particles size,
spherical shape, high encapsulation efficiency (EE %) and sustained SV release.
The results of biological studies revealed that administration of SV loaded NLCs
to rats increased SV bioavailability compared to SV suspension. Intraperitoneal
injection of tyloxapol as hyperlipidemic agent induces a significant increase of
plasma AI, uric acid, lipid peroxidation and protein oxidation. While, plasma
total antioxidant capacity and paraoxonase-1 activity were significantly
decreased. Moreover, tyloxapol induced-hyperlipidemia increases erythrocyte's
membrane cholesterol and deteriorates erythrocyte's antioxidant enzyme activity,
GSH/GSSG ratio and NO level However, the propagation of erythrocyte's pro-oxidant
activity and hemolysis was observed. On the contrast, the treatment of these rats
with SV loaded NLCs improved the measured parameters compared to rats received SV
suspension and hyperlipidemic rats. The predominant effect of SV loaded NLCs may
be attributed to the enhancement of absorption, prolonged duration and
improvement of bioavailability of SV. Accordingly, SV loaded NLCs showed
advantageous effects on the blood lipid levels and atherogenic risk of
erythrocytes in hyperlipidemic conditions compared to SV suspension.
PMID- 27613384
TI - Introduction: Pedagogies of Domestic Violence.
PMID- 27613385
TI - Assessment of epicardial adipose tissue and carotid/femoral intima media
thickness in insulin resistance.
AB - BACKGROUND: Metabolic syndrome is a combination of multiple cardiovascular (CV)
risk factors including insulin resistance (IR). Carotid, femoral intima media
thickness (IMT), and epicardial fat thickness (EFT) are considered as novel
cardiometabolic risk factors. We aimed to test the hypothesis that carotid,
femoral IMT, and EFT are increased in patients with IR. METHODS: We enrolled
consecutively and prospectively 113 patients with IR. Then we collected data from
an age- and sex-matched control group of 112 individuals without IR. Homeostasis
model assessment (HOMA) index value >2.5 was accepted as IR. Patients with
diabetes mellitus, CV diseases, systolic heart failure, chronic liver or renal
diseases were excluded. On B-mode duplex ultrasound the mean IMT at the far wall
of both left and right common carotid/femoral arteries were measured manually.
EFT was measured on the free wall of the right ventricle at end-diastole from the
parasternal long-axis views by standard transthoracic 2D echocardiography.
RESULTS: Both carotid IMT and EFT were significantly higher in patients with IR
compared to controls (0.80+/-0.21mm vs 0.60+/-0.21mm; p<0.001 and 7.34+/-1.96mm
vs 5.22+/-1.75mm; p<0.001, respectively). However, there were no significant
differences in femoral IMT between the groups (0.74+/-0.20 vs 0.69+/-0.17;
p=0.062). In multivariate linear regression analysis age (beta=0.223, p=0.010), 2
h blood glucose (beta=0.198, p=0.021), and IR (beta=0.369, p<0.001) were
independent predictors of EFT. On the other hand age (beta=0.363, p<0.001) and IR
(beta=0.321, p<0.001) were independent predictors of carotid IMT. CONCLUSIONS:
Patients with IR have increased carotid IMT and EFT, but not femoral IMT. This
apparent incoherence may be due to the involvement of carotid arteries prior to
femoral arteries in patients with IR.
PMID- 27613386
TI - Effects of intravenous bolus injection of nicorandil on renal artery flow
velocity assessed by color Doppler ultrasound.
AB - BACKGROUND: Previous animal studies have shown that a potassium channel opener,
nicorandil, provokes vasodilation in renal microvasculature and increases renal
blood flow. We conducted a clinical study that aimed to evaluate the effect of
nicorandil on renal artery blood flow in comparison with nitroglycerin by using
color Doppler ultrasound. METHODS: The present study enrolled 40 patients with
stable coronary artery disease who had no renal arterial stenosis and renal
parenchymal disease. The patients received intravenous administration of
nicorandil (n=20) or nitroglycerin (n=20). Before and after the administration,
renal artery blood flow velocity was measured by color-guided pulsed-wave
Doppler. RESULTS: The peak-systolic, end-diastolic, and mean renal artery blood
flow velocities before the administration were not different between the
nicorandil group and the nitroglycerin group. The peak-systolic (79+/-15cm/s to
99+/-21cm/s, p<0.001; and 78+/-19cm/s to 85+/-19cm/s, p=0.004), end-diastolic
(22+/-5cm/s to 28+/-8cm/s, p<0.001; and 24+/-6cm/s to 26+/-6cm/s, p=0.005) and
mean (41+/-6cm/s to 49+/-9cm/s, p<0.001; and 43+/-9cm/s to 45+/-9cm/s, p=0.009)
renal artery flow velocities increased significantly in either group. The nominal
changes in the peak-systolic (20+/-10cm/s vs. 7+/-8cm/s, p<0.001), end-diastolic
(5+/-4cm/s vs. 2+/-3cm/s, p=0.001), and mean (8+/-5cm/s vs. 2+/-2cm/s, p<0.001)
renal artery blood flow velocities were significantly greater in the nicorandil
group compared with the nitroglycerin group. CONCLUSION: Intravenous nicorandil
increased renal artery blood flow velocity in comparison with nitroglycerin.
Nicorandil has a significant effect on renal hemodynamics.
PMID- 27613387
TI - Does charge-free screening improve detection of gestational diabetes in women
from deprived areas: a cross-sectional study.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) occurs in 2-6 % of all
pregnancies. We investigated whether area level deprivation is associated with a
higher risk for GDM and whether GDM detection rates in deprived regions changed
after the introduction of charge-free GDM screening in Germany in 2012. METHODS:
We analyzed population-based data from Bavaria, Germany, comprising n = 587,621
deliveries in obstetric units between 2008 and 2014. Area level deprivation was
assessed municipality-based using the Bavarian Index of Multiple Deprivation
(BIMD), divided into quintiles and assigned to each mother based on her
residential address. We estimated annual odds ratios (ORs) for GDM diagnosis by
BIMD quintile with adjustment for maternal obesity, maternal age, migration
background and single mother status. RESULTS: Women from the most deprived
regions were less likely to be diagnosed with GDM before introduction of charge
free GDM screening (OR = 0.76 [95 % confidence interval: 0.66, 0.86] compared to
least deprived areas), in 2008. In contrast, high area level deprivation was
associated with significantly increased risk of GDM diagnosis in 2013 (OR [95 %
confidence interval] = 1.15 [1.02, 1.29]). The OR was also elevated, although not
significantly, in 2014 (OR [95 % confidence interval] = 1.05 [0.93, 1.18]).
CONCLUSIONS: The prevalence of GDM seems to have been underreported in women from
highly deprived areas before introduction of the charge-free GDM screening in
Germany. In fact, women living in deprived regions seem to have an increased risk
for GDM and may profit from access to charge-free GDM screening.
PMID- 27613389
TI - Genetics of syndromic and non-syndromic hereditary nail disorders.
AB - The nail is a unique epithelial skin appendage made up of a fully keratinized
nail plate. The nail can be affected in several systemic illnesses,
dermatological diseases, and inherited nail disorders. Nail dystrophies can
present as isolated disorders or as a part of syndromes. Substantial progress has
been achieved in the management and diagnosis of nail diseases; however, not much
is known about the underlying molecular controls of nail growth. The homeostasis
and development of the nail appendage depend on the intricate interactions
between the epidermis and underlying mesenchyme, and comprise different signaling
pathways such as the WNT signaling pathway. Digit-tip regeneration in mice and
humans has been a known fact for the past six decades; however, only recently the
underlying biological mechanisms by which the nail organ achieves digit
regeneration have been elucidated. Moreover, significant progress has been made
in identifying nail stem cells and localizing stem cell niches in the nail unit.
More fascinating, however, is the role they play in orchestrating the processes
that lead to the regeneration of the digit. Further elucidating the role of nail
stem cells and the signaling pathways driving epithelial-mesenchymal interactions
in the nail unit might contribute to the development of novel therapeutic tools
for amputees.
PMID- 27613388
TI - Synergistic combinatorial antihyperlipidemic study of selected natural
antioxidants; modulatory effects on lipid profile and endogenous antioxidants.
AB - BACKGROUND: Hyperlipidemia, a major pathological condition associated with
disrupted lipid levels and physiological redox homeostasis. The excessive release
of reactive oxygen species (ROS) leads to enhanced lipid peroxidation, aggravated
atherosclerosis and oxidative stress. Integration of natural antioxidant blends
in alone or with conventional treatments can alleviate these issues
synergistically contributing least side effects. Published literature reported
the efficacy of natural antioxidants as individual and in combinations in various
conditions but less data is available on their evaluation in low dose ratio
blends particularly in hypercholesterolemic diet. METHODS: Antihyperlipidemic
effects of selected natural antioxidants; the phenolic oligomeric
proanthocyanidins (OPC) and pterostilbene (PT) with niacin (NA) were investigated
in current study. Their effects on lipid profile, lipid peroxidation and their
aptitude to establish redox state between oxidants and antioxidants in body were
evaluated in high cholesterol diet fed animal model. Male albino rabbits (n = 6)
weighing 1.2-1.6 kg, supplemented with high cholesterol diet (400 mg/kg) for 12
weeks were used in the experiment. Antioxidants were administered individual high
(100 mg/kg) and in low dose combinations (total dose = 100 mg/kg). Student's t
test and one way analysis of variance (ANOVA) followed by Dunnet's test were used
as statistical tools for evaluation. RESULTS: The results showed synergistic
effects of low dose antioxidant blends. Therapies retarded elevation in blood
lipid levels, lipid peroxidation and blood antioxidant depletion and consequently
contributed in reestablishing redox homeostasis. The LDL/HDL ratio and
atherogenic index were suppressed significantly in blend therapies with maximum
effects of 59.3 and 25 % (p >0.001) observed in 50:30:20 ratios of OPC, NA and
PT, compared to individual therapies 37 and 18 % max respectively. Moreover the
results were also in close proximity with the statin therapy (52.66, 26.28 %).
CONCLUSION: This study provides an evidence for natural antioxidants blends
superiority over individual therapy in chronic diseases like hyperlipidemia. Such
therapies in human equivalent doses can help in mitigating chronic illnesses in
general populations.
PMID- 27613391
TI - Use of Tolvaptan in a Patient With Palliated Congenital Heart Disease.
AB - Heart failure is a common problem in the ever growing population of patients with
palliated congenital heart disease. It is frequently complicated by hyponatremia
that has been associated with increased morbidity and mortality. Tolvaptan is a
vasopressin receptor antagonist that has been effective in improving hyponatremia
and congestive symptoms in adults with chronic heart failure. We describe the
short-term use of tolvaptan to treat hyponatremic hypervolemia in an adolescent
patient with chronic heart failure in the setting of palliated congenital heart
disease prior to definitive surgical intervention. In this case, the patient had
improvement in hyponatremia and a decrease in body weight, without any adverse
effects.
PMID- 27613390
TI - MaGelLAn 1.0: a software to facilitate quantitative and population genetic
analysis of maternal inheritance by combination of molecular and pedigree
information.
AB - BACKGROUND: Identification of genes or even nucleotides that are responsible for
quantitative and adaptive trait variation is a difficult task due to the complex
interdependence between a large number of genetic and environmental factors. The
polymorphism of the mitogenome is one of the factors that can contribute to
quantitative trait variation. However, the effects of the mitogenome have not
been comprehensively studied, since large numbers of mitogenome sequences and
recorded phenotypes are required to reach the adequate power of analysis. Current
research in our group focuses on acquiring the necessary mitochondria sequence
information and analysing its influence on the phenotype of a quantitative trait.
To facilitate these tasks we have produced software for processing pedigrees that
is optimised for maternal lineage analysis. RESULTS: We present MaGelLAn 1.0
(maternal genealogy lineage analyser), a suite of four Python scripts (modules)
that is designed to facilitate the analysis of the impact of mitogenome
polymorphism on quantitative trait variation by combining molecular and pedigree
information. MaGelLAn 1.0 is primarily used to: (1) optimise the sampling
strategy for molecular analyses; (2) identify and correct pedigree
inconsistencies; and (3) identify maternal lineages and assign the corresponding
mitogenome sequences to all individuals in the pedigree, this information being
used as input to any of the standard software for quantitative genetic
(association) analysis. In addition, MaGelLAn 1.0 allows computing the mitogenome
(maternal) effective population sizes and probability of mitogenome (maternal)
identity that are useful for conservation management of small populations.
CONCLUSIONS: MaGelLAn is the first tool for pedigree analysis that focuses on
quantitative genetic analyses of mitogenome data. It is conceived with the
purpose to significantly reduce the effort in handling and preparing large
pedigrees for processing the information linked to maternal lines. The software
source code, along with the manual and the example files can be downloaded at
http://lissp.irb.hr/software/magellan-1-0/ and
https://github.com/sristov/magellan .
PMID- 27613393
TI - Challenges of ECG monitoring and ECG interpretation in dialysis units.
AB - Patients on hemodialysis (HD) suffer from high cardiovascular morbidity and
mortality due to high rates of coronary artery disease and arrhythmias.
Electrocardiography (ECG) is often performed in the dialysis units as part of
routine clinical assessment. However, fluid and electrolyte changes have been
shown to affect all ECG morphologies and intervals. ECG interpretation thus
depends on the time of the recording in relation to the HD session. In addition,
arrhythmias during HD are common, and dialysis-related ECG artifacts mimicking
arrhythmias have been reported. Studies using advanced ECG analyses have examined
the impact of the HD procedure on selected repolarization descriptors and heart
rate variability indices. Despite the challenges related to the impact of the
fluctuant fluid and electrolyte status on conventional and advanced ECG
parameters, further research in ECG monitoring during dialysis has the potential
to provide clinically meaningful and practically useful information for
diagnostic and risk stratification purposes.
PMID- 27613394
TI - Effect of surface treatments on the mechanical properties and antimicrobial
activity of desiccated glass ionomers.
AB - OBJECTIVES: The purpose of this study was to evaluate the effect of various
surface treatments on the mechanical properties and antibacterial activity of
desiccated glass-ionomer (GI) and resin-modified glass-ionomer (RMGI) materials.
METHODS: One hundred GI and RMGI specimens were fabricated in a mold, stored in
100% humidity for 24h, placed in air to desiccate for 24h, and then stored for
one week in one of the five media [casein phosphopeptide-amorphous calcium
phosphate (CPP-ACP), chlorhexidine (CHX), sodium fluoride (NaF), cetylpyridinium
chloride (CPC), or 100% humidity (control)]. Fifty GI and RMGI specimens were
tested in flexure to determine flexural strength and modulus, with the fragments
used for Knoop hardness testing. The remaining 50 GI and RMGI specimens were
covered with a suspension of Streptococcus mutans and incubated for 24h. The
bacterial suspension was removed and the specimens were washed. Sterile saline
was added, vortex mixed, serially diluted, and plated. CFU/mLs were calculated
after 3days of incubation. RESULTS: Compared to the 100% humidity control group,
surface treatment of the desiccated GI and RMGI materials had a variable effect
on the mechanical properties. In general, NaF provided the greatest improvement
in flexural strength and modulus. Surface treatment of the desiccated GI or RMGI
specimens with CHX or CPC resulted in no growth of the S. mutans. NaF resulted in
significantly lower CFU/mL than CPP-ACP, which was significantly lower than the
control group. SIGNIFICANCE: Surface treatment with 5% NaF provides improved
antimicrobial and strength properties of desiccated GI or RMGI materials.
PMID- 27613392
TI - Pharmacological strategies to reduce exacerbation risk in COPD: a narrative
review.
AB - Identifying patients at risk of exacerbations and managing them appropriately to
reduce this risk represents an important clinical challenge. Numerous treatments
have been assessed for the prevention of exacerbations and their efficacy may
differ by patient phenotype. Given their centrality in the treatment of COPD,
there is strong rationale for maximizing bronchodilation as an initial strategy
to reduce exacerbation risk irrespective of patient phenotype. Therefore, in
patients assessed as frequent exacerbators (>1 exacerbation/year) we propose
initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/
long-acting beta2-agonist (LABA). For those patients who continue to experience
>1 exacerbation/year despite maximal bronchodilation, we advocate treating
according to patient phenotype. Based on currently available data on adding
inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA
combination in exacerbating patients who have an asthma-COPD overlap syndrome or
high blood eosinophil counts, while in exacerbators with chronic bronchitis,
consideration should be given to treating with a phosphodiesterase (PDE)-4
inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who
experience frequent bacterial exacerbations and/or bronchiectasis, addition of
mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be
considered. In all patients at risk of exacerbations, pulmonary rehabilitation
should be included as part of a comprehensive management plan.
PMID- 27613396
TI - Erratum to: What do we know? What do we need to know?
PMID- 27613395
TI - Isolated cardiac sarcoidosis: A focused review of an under-recognized entity.
AB - There is accumulating evidence for the existence of a phenotype of isolated
cardiac sarcoidosis (ICS), or sarcoidosis that only involves the heart. In the
absence of biopsy-confirmed cardiac sarcoidosis (CS), existing diagnostic
criteria require the presence of extra-cardiac sarcoidosis as an inclusion
criterion for the diagnosis of CS. Consequently, in the absence of a positive
endomyocardial biopsy, ICS is not diagnosable by current guidelines. Therefore,
there is uncertainty regarding the epidemiology, pathobiology, clinical
characteristics, prognosis, and optimal treatment of ICS. This review will
summarize the available data related to the prevalence and prognosis of ICS and
will discuss challenges surrounding the diagnosis and management of this under
recognized entity.
PMID- 27613397
TI - Cross-modal plasticity in developmental and age-related hearing loss: Clinical
implications.
AB - This review explores cross-modal cortical plasticity as a result of auditory
deprivation in populations with hearing loss across the age spectrum, from
development to adulthood. Cross-modal plasticity refers to the phenomenon when
deprivation in one sensory modality (e.g. the auditory modality as in deafness or
hearing loss) results in the recruitment of cortical resources of the deprived
modality by intact sensory modalities (e.g. visual or somatosensory systems). We
discuss recruitment of auditory cortical resources for visual and somatosensory
processing in deafness and in lesser degrees of hearing loss. We describe
developmental cross-modal re-organization in the context of congenital or pre
lingual deafness in childhood and in the context of adult-onset, age-related
hearing loss, with a focus on how cross-modal plasticity relates to clinical
outcomes. We provide both single-subject and group-level evidence of cross-modal
re-organization by the visual and somatosensory systems in bilateral, congenital
deafness, single-sided deafness, adults with early-stage, mild-moderate hearing
loss, and individual adult and pediatric patients exhibit excellent and average
speech perception with hearing aids and cochlear implants. We discuss a framework
in which changes in cortical resource allocation secondary to hearing loss
results in decreased intra-modal plasticity in auditory cortex, accompanied by
increased cross-modal recruitment of auditory cortices by the other sensory
systems, and simultaneous compensatory activation of frontal cortices. The
frontal cortices, as we will discuss, play an important role in mediating
cognitive compensation in hearing loss. Given the wide range of variability in
behavioral performance following audiological intervention, changes in cortical
plasticity may play a valuable role in the prediction of clinical outcomes
following intervention. Further, the development of new technologies and
rehabilitation strategies that incorporate brain-based biomarkers may help better
serve hearing impaired populations across the lifespan.
PMID- 27613399
TI - System with embedded drug release and nanoparticle degradation sensor showing
efficient rifampicin delivery into macrophages.
AB - We have developed a biodegradable, biocompatible system for the delivery of the
antituberculotic antibiotic rifampicin with a built-in drug release and
nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on
poly(ethylene oxide) monomethyl ether-block-poly(epsilon-caprolactone) were
noncovalently loaded with rifampicin, a combination that, to best of our
knowledge, was not previously described in the literature, which showed
significant benefits. The nanoparticles contain a Forster resonance energy
transfer (FRET) system that allows real-time assessment of drug release not only
in vitro, but also in living macrophages where the mycobacteria typically reside
as hard-to-kill intracellular parasites. The fluorophore also enables in situ
monitoring of the enzymatic nanoparticle degradation in the macrophages. We show
that the nanoparticles are efficiently taken up by macrophages, where they are
very quickly associated with the lysosomal compartment. After drug release, the
nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88+/
11 min.
PMID- 27613401
TI - Hollow fiber integrated microfluidic platforms for in vitro Co-culture of
multiple cell types.
AB - This study demonstrates a rapid prototyping approach for fabricating and
integrating porous hollow fibers (HFs) into microfluidic device. Integration of
HF can enhance mass transfer and recapitulate tubular shapes for tissue
engineered environments. We demonstrate the integration of single or multiple
HFs, which can give the users the flexibility to control the total surface area
for tissue development. We also present three microfluidic designs to enable
different co-culture conditions such as the ability to co-culture multiple cell
types simultaneously on a flat and tubular surface, or inside the lumen of
multiple HFs. Additionally, we introduce a pressurized cell seeding process that
can allow the cells to uniformly adhere on the inner surface of HFs without
losing their viabilities. Co-cultures of lung epithelial cells and microvascular
endothelial cells were demonstrated on the different platforms for at least five
days. Overall, these platforms provide new opportunities for co-culturing of
multiple cell types in a single device to reconstruct native tissue micro
environment for biomedical and tissue engineering research.
PMID- 27613398
TI - Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.
AB - A diverse group of genes are involved in the tooth development of mammals.
Several studies, focused mainly on mice and rats, have provided a detailed
depiction of the processes coordinating tooth formation and shape. Here we
surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for
signatures of selection to assess patterns of molecular adaptation in genes
regulating mammalian dentition. Of the 236 genes, 31 (~13.1%) showed strong
signatures of positive selection that may be responsible for the phenotypic
diversity observed in mammalian dentition. Mammalian-specific tooth-associated
genes had accelerated mutation rates compared with older genes found across all
vertebrates. More recently evolved genes had fewer interactions (either genetic
or physical), were associated with fewer Gene Ontology terms and had faster
evolutionary rates compared with older genes. The introns of these positively
selected genes also exhibited accelerated evolutionary rates, which may reflect
additional adaptive pressure in the intronic regions that are associated with
regulatory processes that influence tooth-gene networks. The positively selected
genes were mainly involved in processes like mineralization and structural
organization of tooth specific tissues such as enamel and dentin. Of the 236
analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on
diversification of mammalian teeth as they have higher evolutionary rates and
exhibit different expression profiles compared with older genes. Our results
suggest that the evolution and development of mammalian dentition occurred in
part through positive selection acting on genes that previously had other
functions.
PMID- 27613400
TI - Is REDD1 a Metabolic Eminence Grise?
AB - Regulated in development and DNA damage response 1 (REDD1) has been functionally
linked to the control of diverse cellular processes due, at least in part, to its
ability to repress mammalian or mechanistic Target of Rapamycin (mTOR) Complex-1
(mTORC1), a key protein complex controlled by hormonal and nutrient cues.
Notably, emerging evidence suggests that REDD1 also regulates several pathways
involved in modulating energy balance and metabolism. Herein, we discuss evidence
implicating REDD1 as a key modulator of insulin action and metabolic function,
including its potential contribution to mitochondrial biology and pancreatic
islet function. Collectively, the available evidence suggests that REDD1 has a
more prominent role in energy homeostasis than was previously thought, and
implicates REDD1 as a potential therapeutic target for treatment of metabolic
disorders.
PMID- 27613402
TI - Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T
cell functions: Possible application in the inhibition of melanoma tumor growth
in mice.
AB - Regulatory T (Treg) cells are important to induce and maintain immunological self
tolerance. Although the progress accomplished in understanding the functional
mechanism of Treg cells, intracellular molecules that control the mechanisms of
their suppressive capacity are still on investigation. The present study showed
that peroxisome proliferator-activated receptor-alpha deficiency impaired the
suppressive activity of Treg cells on CD4+CD25- and CD8+ T cell proliferation. In
Treg cells, PPARalpha gene deletion also induced a decrease of migratory
abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8
and CXCR-4) and p27KIP1 mRNA. Treg cells from PPARalpha-/- mice also lost their
anergic property. Since low Treg activity, as observed in PPARalpha-/- mice, is
known to be associated with the inhibition of tumor growth, we inoculated these
mice with B16 melanoma cells and assessed tumor proliferation. In PPARalpha-/-
mice, cancer growth was significantly curtailed, and it was correlated with high
expression of granzyme B and perforin mRNA in tumor bed. Degranulation of
cytolytic molecules by CD8+ T cells, assessed by a perforin-release marker CD107a
expression, was higher in PPARalpha-/- mice than that in wild-type mice. Tumor
infiltrating lymphocytes (TIL) in melanoma tumors in PPARalpha-/- mice exhibited
high pro-inflammatory Th1 phenotype. Consistently, adoptive transfer into
lymphopenic RAG2-/- mice of total PPARalpha-/-splenic T cells inhibited more the
growth rate of B16 tumor than the wild type splenic T cells. Our findings suggest
that PPARalpha deficiency, by diminishing Treg cell functions and upregulating
pro-inflammatory T cell phenotype, exerts an in vivo anti-cancer properties.
PMID- 27613403
TI - Global analysis of VHHs framework regions with a structural alphabet.
AB - The VHHs are antigen-binding region/domain of camelid heavy chain antibodies
(HCAb). They have many interesting biotechnological and biomedical properties due
to their small size, high solubility and stability, and high affinity and
specificity for their antigens. HCAb and classical IgGs are evolutionary related
and share a common fold. VHHs are composed of regions considered as constant,
called the frameworks (FRs) connected by Complementarity Determining Regions
(CDRs), a highly variable region that provide interaction with the epitope.
Actually, no systematic structural analyses had been performed on VHH structures
despite a significant number of structures. This work is the first study to
analyse the structural diversity of FRs of VHHs. Using a structural alphabet that
allows approximating the local conformation, we show that each of the four FRs do
not have a unique structure but exhibit many structural variant patterns.
Moreover, no direct simple link between the local conformational change and amino
acid composition can be detected. These results indicate that long-range
interactions affect the local conformation of FRs and impact the building of
structural models.
PMID- 27613404
TI - Arsenic trioxide-induced osteo-necrosis treatment in a child: mini-review and
case report.
AB - BACKGROUND: Arsenic oxide compounds were traditionally used as devitalizing
agents. Due to its toxicity, leakage of such compounds into the periodontium can
cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA
for decades, however, some dentists seem to still use it. CASE REPORT: We report
the case of a 14-year-old girl referred to the paediatric dentistry department of
Toulouse University hospital, France, presenting a bone necrosis following the
use of an arsenic trioxide product to accelerate pulp necrosis. TREATMENT: The
treatment included surgical removal of necrosis bone sequestrum, complete
pulpectomy and an intermediate restoration of the tooth 27. FOLLOW-UP: After 1
week, the clinical conditions greatly improved. A restoration using a ceramic
crown was performed after 2 months, and complete healing was observed after 1
year follow-up. CONCLUSION: Although arsenic trioxide is neither appropriate nor
permitted for use in modern dentistry, especially in paediatric dentistry, some
rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer
message must be given to all dental practitioners against the use of arsenic
trioxide in modern endodontic treatment.
PMID- 27613405
TI - Periodontal disease detection in primary and mixed dentitions.
AB - AIM: This was to compare the periodontal status of children with primary and
mixed dentition at the time of their first consultation. METHODS: Children (200),
aged 0-12 years (156 with mixed and 44 with primary dentition), were examined by
assessing their simplified plaque index (PI) and simplified periodontal record
(PSR). Statistical analysis (Chi-square test) was performed with appropriate
software to find any significant associations between sex, type of dentition and
PI with the PSR codes (0, 1, 2, 3 and 4). RESULTS: There was no statistically
significant difference with regard to gender (p = 0.82). Generalised PI was
associated more significantly with mixed dentition (p = 0.025 and higher PSR
scores (p < 0.001). There was no significant relationship between sex and PSR
codes (p = 0.82). CONCLUSION: Children presenting with a mixed dentition had
worse PI values and PSR scores. It is important to perform periodontal
examination in children to diagnose and prevent future periodontal disease and
maintain their dentition as well as to identify any associated systemic
conditions.
PMID- 27613406
TI - Metabolic engineering for isopropanol production by an engineered cyanobacterium,
Synechococcus elongatus PCC 7942, under photosynthetic conditions.
AB - Cyanobacteria engineered for production of biofuels and biochemicals from carbon
dioxide represent a promising area of research in relation to a sustainable
economy. Previously, we have succeeded in producing isopropanol from cellular
acetyl-CoA by means of Synechococcus elongatus PCC 7942 into which a synthetic
metabolic pathway was introduced. The isopropanol production by this synthetic
metabolic pathway requires acetate; therefore, the cells grown under
photosynthetic conditions have to be transferred to a dark and anaerobic
conditions to produce acetate. In this study, we achieved acetate production
under photosynthetic conditions by S. elongatus PCC 7942 into which we introduced
the pta gene encoding phosphate acetyltransferase from Escherichia coli. The
metabolic modification (via pta introduction) of the isopropanol-producing strain
enabled production of isopropanol under photosynthetic conditions. During 14 days
of production, the titer of isopropanol reached 0.55 mM (33.1 mg/l) with an
intermediate product, acetone, at 0.21 mM (12.2 mg/l).
PMID- 27613407
TI - A potential role for CCN2/CTGF in aggressive colorectal cancer.
AB - CCN2, also known as connective tissue growth factor (CTGF) is a transcriptional
target of TGF-beta signaling. Unlike its original name ("CTGF") suggested, CCN2
is not an actual growth factor but a matricellular protein that plays an
important role in fibrosis, inflammation and connective tissue remodeling in a
variety of diseases, including cancer. In pancreatic ductal adenocarcinoma, CCN2
signaling induces stromal infiltration and facilitates a strong tumor-stromal
interaction. In many types of cancer, CCN2 overexpression has been associated
with poor outcome. CMS4 (Consensus Molecular Subtype 4) is a recently identified
aggressive colorectal cancer subtype, that is characterized by up-regulation of
genes involved in epithelial-to-mesenchymal transition, TGF-beta signaling,
angiogenesis, complement activation, and extracellular matrix remodeling. In
addition, a high influx of stromal fibroblasts contributes to the mesenchymal
like gene expression profile of this subtype. Furthermore, compared with the
other three CMS groups, CMS4 tumors have the worst prognosis. Based on these
observations, we postulated that CCN2 might contribute to colorectal cancer
progression, especially in the CMS4 subtype. This review discusses the available
literature on the role of CCN2 in colorectal cancer, with a focus on the
'fibrotic subtype' CMS4.
PMID- 27613408
TI - Celiac anti-type 2 transglutaminase antibodies induce differential effects in
fibroblasts from celiac disease patients and from healthy subjects.
AB - Type 2 transglutaminase (TG2) has an important pathogenic role in celiac disease
(CD), an inflammatory intestinal disease that is caused by the ingestion of
gluten-containing cereals. Indeed, TG2 deamidates specific gliadin peptides, thus
enhancing their immunogenicity. Moreover, the transamidating activity seems to
provoke an autoimmune response, where TG2 is the main autoantigen. Many studies
have highlighted a possible pathogenetic role of anti-TG2 antibodies, because
they modulate TG2 enzymatic activity and they can interact with cell-surface TG2,
triggering a wide range of intracellular responses. Autoantibodies also alter the
uptake of the alpha-gliadin peptide 31-43 (p31-43), responsible of the innate
immune response in CD, thus partially protecting cells from p31-43 damaging
effects in an intestinal cell line. Here, we investigated whether anti-TG2
antibodies protect cells from p31-43-induced damage in a CD model consisting of
primary dermal fibroblasts. We found that the antibodies specifically reduced the
uptake of p31-43 by fibroblasts derived from healthy subjects but not in those
derived from CD patients. Analyses of TG2 expression and enzymatic activity did
not reveal any significant difference between fibroblasts from healthy and celiac
subjects, suggesting that other features related to TG2 may be responsible of
such different behaviors, e.g., trafficking or subcellular distribution. Our
findings are in line with the concept that a "celiac cellular phenotype" exists
and that TG2 may contribute to this phenotype. Moreover, they suggest that the
autoimmune response to TG2, which alone may damage the celiac mucosa, also fails
in its protective role in celiac cells.
PMID- 27613410
TI - Overview of Dietary Supplements in Prostate Cancer.
AB - Prostate cancer is a key health concern for men with its etiology still under
investigation. Recently, the role of dietary supplements has been noted to have a
major inhibitory effect on prostate cancer and numerous studies have been
conducted in this regard. This review provides a summary on numerous recent
studies conducted in this field. Some of the studies reviewed revealed a
protective role for supplements, and others showed no correlation while some even
had an adverse effect. The mechanism of how these supplements act on the prostate
is still not clear. Further studies are warranted especially for supplements that
have been shown to have a potential inhibitory role in prostate cancer.
PMID- 27613411
TI - Islamic perspectives on clinical intervention near the end-of-life: We can but
must we?
AB - The ever-increasing technological advances of modern medicine have increased
physicians' capacity to carry out a wide array of clinical interventions near the
end-of-life. These new procedures have resulted in new "types" of living where a
patient's cognitive functions are severely diminished although many physiological
functions remain active. In this biomedical context, patients, surrogate decision
makers, and clinicians all struggle with decisions about what clinical
interventions to pursue and when therapeutic intent should be replaced with
palliative goals of care. For some patients and clinicians, religious teachings
about the duty to seek medical care and the care of the dying offer ethical
guidance when faced with such choices. Accordingly, this paper argues that
traditional Sunni Islamic ethico-legal views on the obligation to seek medical
care and Islamic theological concepts of human dignity (karamah) and
inviolability (hurmah) provide the ethical grounds for non-intervention at the
end-of-life and can help calibrate goals of care discussions for Muslim patients.
In closing the paper highlights the pressing need to develop a holistic ethics of
healthcare of the dying from an Islamic perspective that brings together multiple
genres of the Islamic intellectual tradition so that it can meet the needs of the
patients, clinicians and Muslim religious leaders interacting with the healthcare
system.
PMID- 27613409
TI - GCN2- and eIF2alpha-phosphorylation-independent, but ATF4-dependent, induction of
CARE-containing genes in methionine-deficient cells.
AB - Amino-acid deprivation is sensed by the eIF2alpha kinase GCN2. Under conditions
of essential amino-acid limitation, GCN2 phosphorylates eIF2alpha, inhibiting the
formation of a new ternary complex and hence mRNA translation initiation. While
decreasing global mRNA translation, eIF2alpha phosphorylation also increases the
translation of the integrated stress response (ISR) transcription factor ATF4,
which increases the expression of many stress response genes that contain a C/EBP
ATF response element (CARE), including Atf4, 4Ebp1, Asns, and Chop. Using wild
type as well as Gcn2 knockout and unphosphorylatable eIF2alpha mutant MEFs, we
characterized a novel GCN2/eIF2alpha phosphorylation-independent, but ATF4
dependent, pathway that upregulates the expression of CARE-containing genes in
MEFs lacking GCN2 or phosphorylatable eIF2alpha when these cells are exposed to
methionine-deficient, and to a lesser extent arginine- or histidine-deficient,
medium. Thus, we demonstrate a GCN2/eIF2alpha phosphorylation-independent pathway
that converges with the GCN2/eIF2alpha kinase-dependent pathway at the level of
ATF4 and similarly results in the upregulation of CARE-containing genes. We
hypothesize that the essential role of methionine-charged initiator tRNA in
forming ternary complex is responsible for the robust ability of methionine
deficiency to induce ATF4 and the ISR even in the absence of GCN2 or eIF2alpha
kinase activity.
PMID- 27613414
TI - Investigating the determinants of contractor's construction and demolition waste
management behavior in Mainland China.
AB - The abundant generation of construction and demolition (C&D) waste presents a
significant challenge to the sustainable development of the construction industry
in Mainland China. As the implementer of construction activities, the
contractor's C&D waste management performance plays an important role in C&D
waste minimization. This paper aims to investigate the determinants of the
contractor's C&D waste management behavior in Mainland China. The Theory of
Planned Behavior (TPB) was selected as the basis of the theoretical model. In
addition, three contextual constructs (i.e., economic viability, governmental
supervision, and project constraints) were introduced, formulating the initial
model. Based on the initial model, eight constructs were identified and seven
hypotheses were proposed. A questionnaire survey was conducted to collect data
and a Structural Equation Modeling (SEM) analysis was employed to test the
proposed hypotheses. Results showed that the C&D waste management intention is
not a significant determinant of contractor's C&D waste management behavior. The
most important determinant is economic viability, followed by governmental
supervision as the second most important determinant. Nevertheless, the construct
of project constraints is an insignificant determinant for contractor's adoption
of C&D waste management behavior. The research findings imply that, in Mainland
China, the government, at this stage, plays an important role in guiding and
promoting the contractor to exhibit better C&D waste management behavior.
PMID- 27613412
TI - Isolation of TGF-beta-neutralizing single-domain antibodies of predetermined
epitope specificity using next-generation DNA sequencing.
AB - The epitope specificity of therapeutic antibodies is often critical to their
efficacy and mode of action. Here, we report the isolation of single-domain
antibodies (sdAbs) against a pre-specified epitope of TGF-beta3: namely, the site
of interaction between the cytokine and its cell-surface type II receptor. By
panning a phage-displayed immune llama VhH library against TGF-beta3 using
competitive elution with soluble dimeric type II receptor ectodomain in tandem
with next-generation DNA sequencing, we identified several sdAbs that competed
with the receptor for TGF-beta3 binding and neutralized TGF-beta3 in in vitro
cellular assays. In contrast, all other sdAbs identified using conventional
panning approaches (i.e., without regard to epitope specificity) did not target
the site of receptor:cytokine interaction. We expect this strategy to be
generally applicable for identifying epitope-specific sdAbs when binding reagents
directed against the epitope of interest are available. The sdAbs identified here
are of potential interest as cancer immunotherapeutics.
PMID- 27613415
TI - Can persuasive and demonstrative messages to visitors reduce littering in river
beaches?
AB - Littering of public areas is a significant problem worldwide. Here we evaluate
the success of persuasive and demonstrative messages at reducing littering in
highly visited river beaches in Argentina. We made an intervention at the beaches
which consisted of a personalized verbal request asking visitors to take their
litter to the waste cans (persuasive message) while they were exposed to the
example of picking up the litter already left on the beach (demonstrative
message). We conducted 102 observations distributed over 29 dates, two years and
four beaches. Each observation consisted of three or four rounds: before the
presence of visitors we cleaned the beaches, during the stay of visitors we made
the intervention (once or twice) in two out of the four beaches, and early next
morning we estimated the amount of litter left per beach. Litter weight ranged
from 0 to 53gvisitor-1day-1. Littering per visitor was reduced an average of 35%
due to the intervention (p=0.049). We also found differences among beaches
(p=0.001), and an increase in littering with crowding (p=0.005). We show for the
first time that the personalized request combined with the example of picking up
litter is effective in reducing littering in a Latin American country.
PMID- 27613416
TI - Solidification and immobilization of MSWI fly ash through aluminate
geopolymerization: Based on partial charge model analysis.
AB - This study presents an integrated synopsis of the solidification and
immobilization mechanisms of fly ash-based geopolymers. A rational analysis of
the ion reactions involved in geopolymerization was conducted using the partial
charge model (PCM). The following conclusions were obtained: (1) heavy metal
cations cannot be immobilized as counter cations through exchange with Na+; (2)
isomorphous substitution of heavy metals in the geopolymer can be expected from
the condensation reaction between the hydrolyzed heavy metal species and
aluminosilicate; (3) the hydrolyzed species condensation could result in
solidification and immobilization and be promoted by aluminates; and (4) a
geopolymer with the highest immobilization and solidification efficiency can be
obtained at an intermediate pH value. The partial charges on the framework of Si,
Al, and O in the primary building blocks of aluminosilicate and heavy metal-doped
aluminosilicate were confirmed through XPS and 29Si NMR spectroscopy analyses.
The effects of activator dosage and types on fly ash-based geopolymers were also
investigated, and the results verify the PCM analysis. A geopolymer with the
highest strength was produced at an intermediate alkaline dosage. Silicate or
aluminate introduced into the activator improved the strength and immobilization
efficiency, and aluminate exhibited better performance. Heavy metals bound to the
exchangeable or acid-soluble fraction were transformed into aluminosilicate
species during geopolymerization.
PMID- 27613417
TI - The genomes of three North American orthopoxviruses.
AB - The complete genomes of a skunkpox, volepox, and raccoonpox virus were sequenced
and annotated. Phylogenetic analysis of these genomes indicates that although
these viruses are all orthopoxviruses, they form a distinct clade to the other
known species. This supports the ancient divergence of the North American
orthopoxviruses from other members of the orthopoxviruses. Only two open reading
frames appear to be unique to this group of viruses, but a relatively small
number of insertions/deletions contribute to the varied gene content of this
clade. The availability of these genomes will help determine whether skunkpox and
volepox viruses share the characteristics that make raccoonpox a useful vaccine
vector.
PMID- 27613419
TI - Arginine methylation promotes translation repression activity of eIF4G-binding
protein, Scd6.
AB - Regulation of translation plays a critical role in determining mRNA fate. A new
role was recently reported for a subset of RGG-motif proteins in repressing
translation initiation by binding eIF4G1. However the signaling mechanism(s) that
leads to spatial and temporal regulation of repression activity of RGG-motif
proteins remains unknown. Here we report the role of arginine methylation in
regulation of repression activity of Scd6, a conserved RGG-motif protein. We
demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an
important role in its methylation. We identify specific methylated arginine
residues in the Scd6 RGG-motif in vivo We provide evidence that methylation
augments Scd6 repression activity. Arginine methylation defective (AMD) mutant of
Scd6 rescues the growth defect caused by overexpression of Scd6, a feature of
translation repressors in general. Live-cell imaging of the AMD mutant revealed
that it is defective in inducing formation of stress granules. Live-cell imaging
and pull-down results indicate that it fails to bind eIF4G1 efficiently.
Consistent with these results, a strain lacking Hmt1 is also defective in Scd6
eIF4G1 interaction. Our results establish that arginine methylation augments Scd6
repression activity by promoting eIF4G1-binding. We propose that arginine
methylation of translation repressors with RGG-motif could be a general modulator
of their repression activity.
PMID- 27613418
TI - PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung
adenocarcinoma progression by targeting oncogenic protein JMJD6.
AB - HOXB9 is a homeobox domain-containing transcription factor, playing an important
role in embryonic development and cancer progression. However, the precise post
translational modifications (PTMs) of HOXB9 and the corresponding roles are
unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF)
interacts with and acetylates HOXB9 both in vivo and in vitro Conversely, the
acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found
that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the
wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell
migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the
transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by
direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated
HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma
patients. Taken together, we identified the first PTM of HOXB9 by demonstrating
that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild
type HOXB9 in regulating lung adenocarcinoma progression.
PMID- 27613420
TI - PCDDB: new developments at the Protein Circular Dichroism Data Bank.
AB - The Protein Circular Dichroism Data Bank (PCDDB) has been in operation for more
than 5 years as a public repository for archiving circular dichroism
spectroscopic data and associated bioinformatics and experimental metadata. Since
its inception, many improvements and new developments have been made in data
display, searching algorithms, data formats, data content, auxillary information,
and validation techniques, as well as, of course, an increase in the number of
holdings. It provides a site (http://pcddb.cryst.bbk.ac.uk) for authors to
deposit experimental data as well as detailed information on methods and
calculations associated with published work. It also includes links for each
entry to bioinformatics databases. The data are freely available to accessors
either as single files or as complete data bank downloads. The PCDDB has found
broad usage by the structural biology, bioinformatics, analytical and
pharmaceutical communities, and has formed the basis for new software and methods
developments.
PMID- 27613421
TI - Transcription-coupled changes to chromatin underpin gene silencing by
transcriptional interference.
AB - Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently
results in transcriptional interference. However, the mechanism of this
repression is not fully understood. We recently showed that drug tolerance in
fission yeast Schizosaccharomyces pombe is controlled by lncRNA transcription
upstream of the tgp1+ permease gene. Here we demonstrate that transcriptional
interference of tgp1+ involves several transcription-coupled chromatin changes
mediated by conserved elongation factors Set2, Clr6CII, Spt6 and FACT. These
factors are known to travel with RNAPII and establish repressive chromatin in
order to limit aberrant transcription initiation from cryptic promoters present
in gene bodies. We therefore conclude that conserved RNAPII-associated mechanisms
exist to both suppress intragenic cryptic promoters during genic transcription
and to repress gene promoters by transcriptional interference. Our analyses also
demonstrate that key mechanistic features of transcriptional interference are
shared between S. pombe and the highly divergent budding yeast Saccharomyces
cerevisiae Thus, transcriptional interference is an ancient, conserved mechanism
for tightly controlling gene expression. Our mechanistic insights allowed us to
predict and validate a second example of transcriptional interference involving
the S. pombe pho1+ gene. Given that eukaryotic genomes are pervasively
transcribed, transcriptional interference likely represents a more general
feature of gene regulation than is currently appreciated.
PMID- 27613423
TI - Comparison of Selenium Toxicity in Sunflower and Maize Seedlings Grown in
Hydroponic Cultures.
AB - Several studies have demonstrated that selenium (Se) at low concentrations is
beneficial, whereas high Se concentrations can induce toxicity. Controlling Se
uptake, metabolism, translocation and accumulation in plants is important to
decrease potential health risks and helping to select proper biofortification
methods to improve the nutritional content of plant-based foods. The uptake and
distribution of Se, changes in Se content, and effects of various concentrations
of Se in two forms (sodium selenite and sodium selenate) on sunflower and maize
plants were measured in nutrient solution experiments. Results revealed the Se
content in shoots and roots of both sunflower and maize plants significantly
increased as the Se level increased. In this study, the highest exposure
concentrations (30 and 90 mg/L, respectively) caused toxicity in both sunflower
and maize. While both Se forms damaged and inhibited plant growth, each behaved
differently, as toxicity due to selenite was observed more than in the selenate
treatments. Sunflower demonstrated a high Se accumulation capacity, with higher
translocation of selenate from roots to shoots compared with selenite. Since in
seleniferous soils, a high change in plants' capability exists to uptake Se from
these soils and also most of the cultivated crop plants have a bit tolerance to
high Se levels, distinction of plants with different Se tolerance is important.
This study has tried to discuss about it.
PMID- 27613424
TI - In vitro production of baculoviruses: identifying host and virus genes associated
with high productivity.
AB - Baculoviruses are recognized as viral workhorses of biotechnology, being used for
production of vaccines, complex recombinant proteins, gene delivery vectors' and
safe biological pesticides. Improving production yields and understanding the
interactions of the virus and its host cell are important aspects of ensuring
baculovirus-based processes are commercially competitive. This study aims at
potential optimization of host cells used in in vitro virus production by
systemically investigating changes in host gene expression in response to virus
replication and transcription inside host cells. The study focuses on in vitro
interactions of the Helicoverpa armigera virus with Helicoverpa zea insect cells.
We used 22 genome-wide microarrays to simultaneously measure both virus and host
genes in infected cells in multiple batch suspension cultures, representing high-
and low-producing infection conditions. Among 661 differentially expressed genes,
we identified a core set of 59 host genes consistently overexpressed post
infection, with strong overrepresentation of genes involved in
retrotransposition, protein processing in the endoplasmic reticulum, and
ubiquitin-mediated proteolysis. Applying a whole genome correlation network
analysis to link gene expression to productivity, we revealed 18 key genes
significantly associated to virus yield. In addition, this study is among the
first to perform a genome-wide expression study for a major baculovirus group II
strain, the H. armigera virus, extending current understanding of baculovirus
insect interactions, which mainly focuses on group I viruses.
PMID- 27613422
TI - Child and family health in the era of prevention: new opportunities and
challenges.
AB - To maintain positive health outcomes over the life course, prevention efforts
should begin early in childhood. Two research domains that significantly impact
the trajectory of health over the life course are childhood obesity and early
trauma and violence. Prevention strategies addressing multiple levels of
influence are being adopted in these fields. Childhood obesity prevention efforts
no longer focus solely on individuals, but embrace multiple ecological levels,
such as family, school, and community. Similarly, research on early trauma and
violence has broadened to consider risk and protective factors across domains of
influence. Although we have improved our understanding and prevention of these
two issues, gaps remain in research, practice, and policy. The purpose of this
review is to relay relevant findings that could enhance prevention strategies. We
describe early life and multilevel risk factors relevant to these areas of
research. We also provide recommendations for future efforts to better ensure
good health for generations to come.
PMID- 27613428
TI - Margaret McCartney: General practice is going the way of NHS dentistry.
PMID- 27613426
TI - Population-based imaging biobanks as source of big data.
AB - Advances of computational sciences over the last decades have enabled the
introduction of novel methodological approaches in biomedical research. Acquiring
extensive and comprehensive data about a research subject and subsequently
extracting significant information has opened new possibilities in gaining
insight into biological and medical processes. This so-called big data approach
has recently found entrance into medical imaging and numerous epidemiological
studies have been implementing advanced imaging to identify imaging biomarkers
that provide information about physiological processes, including normal
development and aging but also on the development of pathological disease states.
The purpose of this article is to present existing epidemiological imaging
studies and to discuss opportunities, methodological and organizational aspects,
and challenges that population imaging poses to the field of big data research.
PMID- 27613427
TI - Stress sensitivity of a fission yeast strain lacking histidine kinases is rescued
by the ectopic expression of Chk1 from Candida albicans.
AB - The development of new drugs against the pathogenic yeast Candida albicans is
compelling and the evolution of relevant bioassays is important to achieve this
goal. Promising drug targets are proteins that lack human counterparts which are
true for the His-to-Asp phosphorelay signal transduction systems, important for
stress sensing in bacteria, fungi, and plants. In the pathogenic yeast, Candida
albicans, the CaChk1 histidine kinase is a trigger of the pathway that leads to a
switch from yeast to hyphal growth necessary for invasion. Intriguingly, the
model yeast Schizosaccharomyces pombe has a similar phosphorelay system, with
three histidine kinases named Mak1, Mak2, and Mak3, which are important for the
prevention of aberrant mating and sporulation on rich media. This study uncovered
distinct functions for the three histidine kinases; Mak1 alone or Mak2 and Mak3
together were sufficient for the repression of the meiotic cycle when nutrients
were available. Moreover, strains lacking histidine kinase genes were sensitive
to various types of stress conditions in an auxotrophic strain background, while
the stress sensitivity was lost in prototrophic strains. Finally, the stress
sensitivity of a S. pombe strain that lacks endogenous histidine kinases could be
complemented by the ectopic expression of the CaChk1 histidine kinase from C.
albicans. This finding opens up for the possibility to perform a drug screen with
a biological read-out in S. pombe to find inhibitors of CaChk1.
PMID- 27613429
TI - Congenital renal arteriovenous fistula during the first trimester diagnosed with
ultrasonography.
AB - A case of congenital renal arteriovenous fistula (AVF) complicating pregnancy
with gross hematuria was managed successfully by superselective embolization with
metallic coils. The patient was in the first trimester of her pregnancy at 12
weeks of gestation. The AVF was detected by color Doppler sonography and
confirmed by renal arteriography. Because of its easy accessibility and absence
of irradiation, ultrasound is the first choice for pregnant patients. Color
Doppler ultrasound is effective in diagnosing AVF, and it is also helpful in the
long-term followup after treatment. The cirsoid-type renal congenital
arteriovenous fistula has a characteristic sonographic appearance with a cluster
of tubular anechoic structures in the kidney, which produce continuous turbulent
high-velocity flow signals and a burr-like boundary flow spectrum. When the
sonographic features are present, the diagnosis of renal AVF should be made,
after which renal arteriography can be performed to confirm it. Selective
embolization provided a safe and effective treatment with minimal damage to the
parenchyma and without compromising renal function.
PMID- 27613430
TI - Left ventricular function: time-varying elastance and left ventricular aortic
coupling.
AB - Many aspects of left ventricular function are explained by considering
ventricular pressure-volume characteristics. Contractility is best measured by
the slope, Emax, of the end-systolic pressure-volume relationship. Ventricular
systole is usefully characterized by a time-varying elastance (DeltaP/DeltaV). An
extended area, the pressure-volume area, subtended by the ventricular pressure
volume loop (useful mechanical work) and the ESPVR (energy expended without
mechanical work), is linearly related to myocardial oxygen consumption per beat.
For energetically efficient systolic ejection ventricular elastance should be,
and is, matched to aortic elastance. Without matching, the fraction of energy
expended without mechanical work increases and energy is lost during ejection
across the aortic valve. Ventricular function curves, derived from ventricular
pressure-volume characteristics, interact with venous return curves to regulate
cardiac output. Thus, consideration of ventricular pressure-volume relationships
highlight features that allow the heart to efficiently respond to any demand for
cardiac output and oxygen delivery.
PMID- 27613431
TI - Mutation analysis for the detection of long QT-syndrome (LQTS) associated SNPs.
AB - Congenital long QT-syndrome (LQTS) is an inherited cardiac arrhythmia, which is
characterized by a prolonged QT interval which predisposes to sudden cardiac
death due to ventricular arrhythmias. The altered functions are based on
different mutations in LQTS-associated genes. In this study, we performed a
mutation analysis for the detection of 125 LQTS-associated single nucleotide
polymorphisms (SNPs) focused on the genes KCNQ1, KCNH2, and SCN5A by using the
SNaPshot multiplex minisequencing technique. Furthermore, we investigated 152
autopsy-negative cases from younger adults and infants, as well as samples from
patients with clinically suspicion for LQTS, in which we found two types of
variations.
PMID- 27613432
TI - Incidence and risk factors for aspiration pneumonia after cardiovascular surgery
in elderly patients.
AB - OBJECTIVE: Pneumonia after cardiovascular surgery is the leading cause of
mortality. Postoperative aspiration pneumonia becomes a critical issue in the
management of cardiovascular surgery in the aging society. The aim of this study
was to investigate the incidence and risk factors of aspiration pneumonia after
cardiovascular surgery for elderly patients. METHODS: This study consisted of 123
elderly patients (>65 years old) who survived their final extubation following
cardiovascular surgery at Kinan Hospital. Patients were divided into aspiration
pneumonia and no pneumonia groups. Postoperative aspiration pneumonia was
diagnosed by two independent physicians according to the nursing- and healthcare
associated pneumonia guidelines by the Japanese Respiratory Society. RESULTS:
Among the patients, 12 (9.8 %) had aspiration pneumonia. There were no
differences in patients' characteristics between the groups except for a history
of cerebral vascular disorder (aspiration pneumonia 42 % vs no pneumonia 15 %, p
= 0.04) and ejection fraction (EF) (aspiration pneumonia 56 +/- 21 % vs no
pneumonia 66 +/- 13 %, p = 0.02). Only six (5 %) patients needed more than 12 h
intubation. There was no difference in the operative factors between the groups.
Neurological deficit was more frequently observed in the aspiration pneumonia
group (33 vs 5 %, p = 0.005). Multivariable logistic regression analysis showed
that the history of cerebral vascular disorder and neurological deficit after
surgery was independent risk factors for aspiration pneumonia after
cardiovascular surgery. CONCLUSIONS: Our results could assist in screening
elderly patients who should be more carefully evaluated before oral nutrition to
minimize morbidity and mortality after cardiovascular surgery.
PMID- 27613433
TI - Motor vehicle-related deaths around two major holidays in South Korea.
AB - South Korea has consistently exhibited high rates of motor vehicle-related deaths
(MVDs) since the late 1980s. This study investigated the number of MVDs around
two major public holidays in South Korea-Lunar New Year's Day and Thanksgiving
Day. MVDs from records of all individual deaths in 1997-2014 were extracted;
then, MVDs per day from 14 days before and after each holiday (ie, 29 days in
total) were summed across the years. Eventually, the 3-day mean values of MVDs
before and after the holiday were compared, when holiday-related traffic peaks.
The 3-day mean before Lunar New Year's Day was 385 fatalities, but dropped to 324
after the holiday; the corresponding figures for Thanksgiving Day were 494 and
413. These results are contrary to those of other countries. It appears that the
severe congestion of highway traffic around the holidays resulted in a decrease
in MVDs.
PMID- 27613434
TI - The cost-effectiveness of bike lanes in New York City.
AB - BACKGROUND: Our objective is to evaluate the cost-effectiveness of investments in
bike lanes using New York City's (NYC) fiscal year 2015 investment as a case
study. We also provide a generalizable model, so that localities can estimate
their return on bike lane investments. METHODS AND FINDINGS: We evaluate the cost
effectiveness of bike lane construction using a two-stage model. Our regression
analysis, to estimate the marginal addition of lane miles on the expansion in
bike ridership, reveals that the 45.5 miles of bike lanes NYC constructed in 2015
at a cost of $8 109 511.47 may increase the probability of riding bikes by 9.32%.
In the second stage, we constructed a Markov model to estimate the cost
effectiveness of bike lane construction. This model compares the status quo with
the 2015 investment. We consider the reduced risk of injury and increased
probability of ridership, costs associated with bike lane implementation and
maintenance, and effectiveness due to physical activity and reduced pollution. We
use Monte Carlo simulation and one-way sensitivity analysis to test the
reliability of the base-case result. This model reveals that over the lifetime of
all people in NYC, bike lane construction produces additional costs of $2.79 and
gain of 0.0022 quality-adjusted life years (QALYs) per person. This results in an
incremental cost-effectiveness ratio of $1297/QALY gained (95% CI -$544/QALY
gained to $5038/QALY gained). CONCLUSIONS: We conclude that investments in
bicycle lanes come with an exceptionally good value because they simultaneously
address multiple public health problems. Investments in bike lanes are more cost
effective than the majority of preventive approaches used today.
PMID- 27613436
TI - Distant Space Processing is Controlled by tPA-dependent NMDA Receptor Signaling
in the Entorhinal Cortex.
AB - In humans, spatial cognition and navigation impairments are a frequent situation
during physiological and pathological aging, leading to a dramatic deterioration
in the quality of life. Despite the discovery of neurons with location-specific
activity in rodents, that is, place cells in the hippocampus and later on grid
cells in the entorhinal cortex (EC), the molecular mechanisms underlying spatial
cognition are still poorly known. Our present data bring together in an unusual
combination 2 molecules of primary biological importance: a major neuronal
excitatory receptor, N-methyl-D-aspartate receptor (NMDAR), and an extracellular
protease, tissue plasminogen activator (tPA), in the control of spatial
navigation. By using tPA-deficient mice and a structure-selective pharmacological
approach, we demonstrate that the tPA-dependent NMDAR signaling potentiation in
the EC plays a key and selective role in the encoding and the subsequent use of
distant landmarks during spatial learning. We also demonstrate that this novel
function of tPA in the EC is reduced during aging. Overall, these results argue
for the concept that encoding of proximal versus distal landmarks is mediated not
only by different anatomical pathways but also by different molecular mechanisms,
with the tPA-dependent potentiation of NMDAR signaling in the EC that plays an
important role.
PMID- 27613435
TI - From Shortage to Surge: A Developmental Switch in Hippocampal-Prefrontal Coupling
in a Gene-Environment Model of Neuropsychiatric Disorders.
AB - Cognitive deficits represent a major burden of neuropsychiatric disorders and
result in part from abnormal communication within hippocampal-prefrontal
circuits. While it has been hypothesized that this network dysfunction arises
during development, long before the first clinical symptoms, experimental
evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic
and environmental risk factors of disease (dual-hit GE mice) have poorer
recognition memory that correlates with augmented coupling by synchrony and
stronger directed interactions between prefrontal cortex and hippocampus. The
network dysfunction emerges already during neonatal development, yet it initially
consists in a diminished hippocampal theta drive and consequently, a weaker and
disorganized entrainment of local prefrontal circuits in discontinuous
oscillatory activity in dual-hit GE mice when compared with controls. Thus,
impaired maturation of functional communication within hippocampal-prefrontal
networks switching from hypo- to hyper-coupling may represent a mechanism
underlying the pathophysiology of cognitive deficits in neuropsychiatric
disorders.
PMID- 27613438
TI - Symptom Science: Repurposing Existing Omics Data.
AB - Omics approaches, including genomics, transcriptomics, proteomics, epigenomics,
microbiomics, and metabolomics, generate large data sets. Once they have been
used to address initial study aims, these large data sets are extremely valuable
to the greater research community for ancillary investigations. Repurposing
available omics data sets provides data to address research questions, generate
and test hypotheses, replicate findings, and conduct mega-analyses. Many well
characterized, longitudinal, epidemiological studies collected extensive
phenotype data related to symptom occurrence and severity. While the main
phenotype of interest for many of these studies was often not symptom related,
these data were collected to better understand the primary phenotype of interest.
A search for symptom data (i.e., cognitive impairment, fatigue, gastrointestinal
distress/nausea, sleep, and pain) in the database of genotypes and phenotypes
(dbGaP) revealed many studies that collected symptom and omics data. There is
thus a real possibility for nurse scientists to be able to look at symptom data
over time from thousands of individuals and use omics data to identify key
biological underpinnings that account for the development and severity of
symptoms without recruiting participants or generating any new data. The purpose
of this article is to introduce the reader to resources that provide omics data
to the research community for repurposing, provide guidance on using these
databases, and encourage the use of these data to move symptom science forward.
PMID- 27613437
TI - L-DOPA Oppositely Regulates Synaptic Strength and Spine Morphology in D1 and D2
Striatal Projection Neurons in Dyskinesia.
AB - Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in
striatal medium spiny neurons (MSNs) and increases their excitability. However,
the synaptic changes that occur in MSNs in PD, in particular those induced by
chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly
understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and
dyskinesia model paradigms, enabling cell type-specific assessment of changes in
synaptic physiology and morphology. The distinct fluorescence markers allowed us
to identify D1 and D2 MSNs for analysis using intracellular sharp electrode
recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer
Yellow injections. Dopamine depletion induced spine pruning in both types of
MSNs, affecting mushroom and thin spines equally. Dopamine depletion also
increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude
selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially
affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density
remained reduced but the remaining spines were enlarged, with bigger heads and
larger postsynaptic densities. These morphological changes were accompanied by
facilitation of action potential firing triggered by synaptic inputs. In
contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted
in shortened postsynaptic densities. These changes in D2-MSNs correlated with a
decrease in synaptic transmission. Our findings indicate that L-DOPA-induced
dyskinesia is associated with abnormal spine morphology, modified synaptic
transmission, and altered EPSP-spike coupling, with distinct effects in D1- and
D2-MSNs.
PMID- 27613440
TI - An unusual source of Burkholderia cepacia outbreak in a neonatal intensive care
unit.
AB - During a two-month period, seven preterm infants in our neonatal intensive care
unit (NICU) were found to have sepsis with Burkholderia cepacia demonstrated by
blood culture. A complete environmental investigation was conducted to identify
the source of infection. Caffeine citrate was found to be the source of this
organism. The offending drug was immediately withdrawn from the NICU and the
hospital pharmacy, and local authorities were informed. All seven babies were
discharged with no infection-related morbidities.
PMID- 27613439
TI - The utilization and prognostic impact of B-type Natriuretic Peptide in
hospitalized acute decompensated heart failure in an Asian population.
AB - BACKGROUND: B-type natriuretic peptide (BNP) levels during admission have been
shown to have prognostic value in the diagnosis of heart failure and further
predict the in-hospital mortality of acute decompensated heart failure (ADHF).
This study describes the characteristics of BNP among hospitalized ADHF and
elucidates its prognostic value of in-hospital mortality in an Asian population.
METHODS: We consecutively studied patients aged 20+ who were discharged with a
diagnosis of ADHF from March 2013 to March 2014 in a tertiary hospital of
northern Taiwan by reviewing medical records. Prognostic predictors of mortality
were assessed using Cox proportional hazard regression models. BNP > 100 pg/ml
was used as the cut-off for defining abnormally high BNP based on current
clinical practice criteria. RESULTS: After implementation of our exclusion
criteria, a total of 1,807 patients hospitalized with ADHF were studied. Compared
to those subjects with BNP <=100 pg/ml, individuals with higher BNP tended to
have more advanced age, more clusters of the typical signs of heart failure (HF)
(e.g., peripheral edema or lung rales) at presentation, lower ejection fraction,
lower hemoglobin levels, more disturbed biochemical data, worsened renal
function, and twice the risk for in-hospital mortality (15.2 vs 6.2 %, all p <
0.05). In a multivariate analysis, more advanced age, the presence of rales, a
worse New York Heart Association functional class, wider QRS duration, and
abnormal BNP levels (>100 pg/ml) were all associated with in-hospital mortality
among admitted HF patients after accounting for clinical co-variates and global
ventricular ejection fraction (HR: 2.17, 95 % CI: 1.15-6.64, p = 0.024).
CONCLUSION: Abnormally high BNP levels in ADHF patients during admission were
tightly linked to clinical features of worse physical, functional, and clinical
presentations, and further provided prognostic value for determining in-hospital
mortality among patients with ADHF in an Asian population.
PMID- 27613441
TI - Hepatitis C virus outbreak in a haemodialysis unit: learning from failures.
AB - The investigation of an outbreak of hepatitis C virus in an Italian haemodialysis
(HD) centre showed that three patients acquired infection with the same strain,
affecting a chronically hepatitis C virus (HCV)-infected patient receiving HD in
the same room and during the same shifts. Through our observational analysis many
possible modes of transmission were identified, but none could be definitively
identified as the route of HCV spread in this small cluster. This outbreak
confirms that repeated opportunities for nosocomial HCV transmission may occur
among HD patients due to several breaches in the standard precautions for
bloodborne infections by healthcare staff.
PMID- 27613442
TI - The risks of contamination from tap end filters.
PMID- 27613443
TI - Is the hospital environment friendly for infection control in Poland? Experience
after twenty years of modern infection control.
PMID- 27613445
TI - A comprehensive approach to the molecular determinants of lifespan using a
Boolean model of geroconversion.
AB - Altered molecular responses to insulin and growth factors (GF) are responsible
for late-life shortening diseases such as type-2 diabetes mellitus (T2DM) and
cancers. We have built a network of the signaling pathways that control S-phase
entry and a specific type of senescence called geroconversion. We have translated
this network into a Boolean model to study possible cell phenotype outcomes under
diverse molecular signaling conditions. In the context of insulin resistance, the
model was able to reproduce the variations of the senescence level observed in
tissues related to T2DM's main morbidity and mortality. Furthermore, by
calibrating the pharmacodynamics of mTOR inhibitors, we have been able to
reproduce the dose-dependent effect of rapamycin on liver degeneration and
lifespan expansion in wild-type and HER2-neu mice. Using the model, we have
finally performed an in silico prospective screen of the risk-benefit ratio of
rapamycin dosage for healthy lifespan expansion strategies. We present here a
comprehensive prognostic and predictive systems biology tool for human aging.
PMID- 27613444
TI - Diabetes distress in males and females with type 1 diabetes in adolescence and
emerging adulthood.
AB - BACKGROUND: Age and gender are important factors in the adjustment and
psychological well-being of patients with chronic physical illness. AIM: To
explore the gender and age differences in diabetes distress between adolescents
and emerging adults with type 1 diabetes (T1D). SUBJECTS AND METHODS: Diabetes
distress was compared in 255 adolescents and 283 emerging adults with T1D using
Problem Areas in Diabetes scale. RESULTS: High diabetes distress level was found
in 22.8% of participants. Lack of confidence in self-care (6.0 vs 3.0, p=0.002),
negative emotional consequences (10.0 vs 6.0, p=0.004), and overall score (18.75
vs 11.25, p=0.002) were higher in adult than in adolescent males, when adjusted
for age at T1D onset. Negative emotional consequences (13.0 vs 10.0, p=0.005) and
overall score (25.0 vs 20.0, p=0.016) were higher in adult compared to adolescent
females, when adjusted for age at T1D onset. Lack of confidence in self-care (6.0
vs 3.0, p=0.002), negative emotional consequences (10.0 vs 6.0, p=0.015), and
overall score (20.0 vs 11.2, p=0.005) were higher in adolescent females compared
to males, when adjusted for age at T1D onset. Negative emotional consequences
score was higher in adult females compared to males (13.0 vs 10.0, p=0.029), when
adjusted for age at T1D onset. In conclusion, our findings show that patients
with T1D have greater burden of diabetes distress in emerging adulthood than in
adolescence and add to evidence suggesting the importance of addressing diabetes
distress in clinical care and the necessity of wider picture beyond the physical
manifestation of diabetes to be taken into consideration.
PMID- 27613446
TI - Dehydration rate determines the degree of membrane damage and desiccation
tolerance in bryophytes.
AB - Desiccation tolerant (DT) organisms are able to withstand an extended loss of
body water and rapidly resume metabolism upon rehydration. This ability, however,
is strongly dependent on a slow dehydration rate. Fast dehydration affects
membrane integrity leading to intracellular solute leakage upon rehydration and
thereby impairs metabolism recovery. We test the hypothesis that the increased
cell membrane damage and membrane permeability observed under fast dehydration,
compared with slow dehydration, is related to an increase in lipid peroxidation.
Our results reject this hypothesis because following rehydration lipid
peroxidation remains unaltered, a fact that could be due to the high increase of
NO upon rehydration. However, in fast-dried samples we found a strong signal of
red autofluorescence upon rehydration, which correlates with an increase in ROS
production and with membrane leakage, particularly the case of phenolics. This
could be used as a bioindicator of oxidative stress and membrane damage.
PMID- 27613447
TI - Age estimation of immature human skeletal remains from the metaphyseal and
epiphyseal widths of the long bones in the post-natal period.
AB - OBJECTIVES: This study provides regression and classical calibration models for
the estimation of age from the dimensions of the metaphyses and epiphyses of the
six long bones. METHODS: A sample of 148 known sex and age individuals (56
females and 92 males), aged between birth and 12 years of age, selected from
Portuguese and English skeletal collections. Age estimation models were obtained
separately for each sex and for the sexes combined, for the entire sample and for
the sample divided into two subsamples at the age of 2 years. RESULTS: The best
performing epiphysis is the proximal epiphysis of the tibia. For the metaphyses,
the distal metaphysis of the tibia and the proximal metaphysis of the femur are
best for individuals below and above 2 years of age, respectively. Growth of the
metaphyses is similar to that of the diaphysis. Results suggest that age can be
as accurately estimated from the width of the metaphyses and epiphyses as from
the length of the diaphyses, or as from the length of the deciduous and permanent
teeth. CONCLUSIONS: These models may be useful for fragmentary material in both
archaeological and forensic contexts. However, due to the background of the
samples, the models would be most applicable to individuals exposed to adverse
environmental conditions during growth and development. Metaphyseal and
epiphyseal widths may be less affected by ecological conditions than diaphyseal
length.
PMID- 27613448
TI - Opportunities and Challenges Facing the Integrated Physician Workforce of
Emergency Medicine and Hospice and Palliative Medicine.
AB - BACKGROUND: The American Board of Emergency Medicine joined nine other American
Board of Medical Specialties member boards to sponsor the subspecialty of Hospice
and Palliative Medicine; the first subspecialty examination was administered in
2008. Since then an increasing number of emergency physicians has sought this
certification and entered the workforce. There has been limited discussion
regarding the experiences and challenges facing this new workforce. DISCUSSION:
We use excerpts from conversations with emergency physicians to highlight the
challenges in hospice and palliative medicine training and practice that are
commonly being identified by these physicians, at varying phases of their
careers. The lessons learned from this initial dual-certified physician cohort in
real practice fills a current literature gap. Practical guidance is offered for
the increasing number of trainees and mid-career emergency physicians who may
have an interest in the subspecialty pathway but are seeking answers to what a
future integrated practice will look like in order to make informed career
decisions. CONCLUSION: The Emergency and Hospice and Palliative Medicine
integrated workforce is facing novel challenges, opportunities, and growth. The
first few years have seen a growing interest in the field among emergency
medicine resident trainees. As the dual certified workforce matures, it is
expected to impact the clinical practice, research, and education related to
emergency palliative care.
PMID- 27613449
TI - Axilloaxillary Arteriovenous Fistula Caused by Previous Penetrating Trauma.
AB - BACKGROUND: Traumatic axilloaxillary arteriovenous (AV) fistulas are rare
occurrences, with the predominance of AV fistulas in this region occurring as an
alternative surgical intervention in patients who are undergoing hemodialysis.
CASE REPORT: We describe the case of a young man with this condition caused by a
previous penetrating trauma who had a delayed diagnosis primarily because of the
infrequency of the clinical presentation. This is one of a few documented cases
of axilloaxillary AV fistulas in the setting of trauma. WHY SHOULD AN EMERGENCY
PHYSICIAN BE AWARE OF THIS?: Axilloaxillary AV fistulas present with loud
machinery like cardiac murmurs that can be similar to patients with coarctation
of the aorta and patent ductus arteriosus; however, important clinical
examination features can help distinguish the two conditions. Diagnosis is
important in avoiding late-stage complications and more technically difficult
surgical repairs.
PMID- 27613450
TI - In Support of the Medical Apology: The Nonlegal Arguments.
AB - BACKGROUND: More than 30 million people are affected annually by medical errors.
Apologies can heal patients, families, and providers and, if deployed and
structured appropriately, can enrich clinical encounters-yet they rarely occur.
OBJECTIVES: This article will address the nonlegal arguments in favor of the
medical apology and discuss a structure for delivering a meaningful apology. In
addition, we will review reasons why some providers feel compelled to apologize
while others faced with similar circumstances do not. DISCUSSION: Medical
apologies bring value to both patients and providers. Apologies can preserve
therapeutic relationships and save careers for professionals by restoring their
self-respect and dignity. The four R's of the ideal apology-recognition,
responsibility, regret, and remedy-provide a framework to help providers
apologize for unintended outcomes. When deployed and structured appropriately,
apologies can heal patients, families, and providers and can enrich clinical
encounters. CONCLUSION: For providers, forgiving one's self is key to
professional wellbeing and continued effective practice. For patients, apologies
are desirable and also serve as a conduit for often wanted emotional support from
their physician.
PMID- 27613451
TI - A bootstrap approach to implementation science.
PMID- 27613452
TI - Empty nose syndrome and atrophic rhinitis.
PMID- 27613453
TI - Ataxia telangiectasia presenting as hyper IgM syndrome without neurologic signs.
PMID- 27613454
TI - Chronic food protein-induced enterocolitis syndrome: Characterization of clinical
phenotype and literature review.
PMID- 27613455
TI - Chronic rhinosinusitis phenotypes.
AB - OBJECTIVE: To review the current knowledge surrounding different chronic
rhinosinusitis (CRS) presentations and the relative roles of nasal polyps,
eosinophilia, and allergies in discerning phenotypes. DATA SOURCES: PubMed
literature review. STUDY SELECTIONS: Articles discussing the various phenotypes
of CRS with emphasis on pathologic and immune mechanistic studies that
distinguish disease. RESULTS: Current guidelines primarily separate CRS based on
the presence or absence of nasal polyps. This is largely driven by the tendency
of eosinophilic disease to present with nasal polyps (NPs) in contrast to
noneosinophilic presentations, which less often lead to the development NPs.
Further separations have been proposed based on expression of aeroallergen
sensitization. CONCLUSION: The presence of NPs may only poorly predict the
presence of an underlying eosinophilic process and as such may have poor utility
in forming the basis for recommending eosinophil-target therapies. Similarly,
there is little evidence to support a significant role for aeroallergen exposure
in contributing to the presence, severity, or natural history of CRS. Appropriate
separation of CRS into specific phenotypes will allow therapeutic approaches to
be individualized to each distinct presentation.
PMID- 27613456
TI - Telemedicine is as effective as in-person visits for patients with asthma.
AB - BACKGROUND: Access to asthma specialists is a problem, particularly in rural
areas, thus presenting an opportunity for management using telemedicine.
OBJECTIVE: To compare asthma outcomes during 6 months in children managed by
telemedicine vs in-person visits. METHODS: Children with asthma residing in 2
remote locations were offered the choice of an in-person visit or a telemedicine
session at a local clinic. The telemedicine process involved real-time use of a
Remote Presence Solution (RPS) equipped with a digital stethoscope, otoscope, and
high-resolution camera. A telefacilitator operated the RPS and performed
diagnostic and educational procedures, such as spirometry and asthma education.
Children in both groups were assessed initially, after 30 days, and at 6 months.
Asthma outcome measures included asthma control using validated tools (Asthma
Control Test, Childhood Asthma Control Test, and Test for Respiratory and Asthma
Control in Kids) and patient satisfaction (telemedicine group only).
Noninferiority analysis of asthma control was performed using the minimally
important difference of an adjusted asthma control test that combined the 3 age
groups. RESULTS: Of 169 children, 100 were seen in-person and 69 via
telemedicine. A total of 34 in-person and 40 telemedicine patients completed all
3 visits. All had a small, although statistically insignificant, improvement in
asthma control over time. Telemedicine was noninferior to in-person visits. Most
of the telemedicine group subjects were satisfied with their experience.
CONCLUSION: Children with asthma seen by telemedicine or in-person visits can
achieve comparable degrees of asthma control. Telemedicine can be a viable
alternative to traditional in-person physician-based care for the treatment and
management of asthma.
PMID- 27613457
TI - The effect of a holding chamber on albuterol metered-dose inhaler product
differences.
AB - BACKGROUND: Three albuterol sulfate metered-dose inhaled (MDI) products (Ventolin
HFA, Proventil HFA, and ProAir HFA) are marketed in the United States to provide
the same total dose of albuterol sulfate. However, it is widely known that the
fine particle dose (<5 MUm) is the portion of the particle distribution that
actually reaches the lungs and provides therapeutic benefit. OBJECTIVE: To
examine the differences in particle size between products and how a valved
holding chamber (VHC) can mitigate possible adverse effects. METHODS: Particle
size distributions in each product were measured, with and without a VHC, and
were analyzed by high-performance liquid chromatography. RESULTS: The only
significant mean (SD) difference in total dose was between Proventil (75 [21]
MUg) and ProAir (107 [12] MUg) (P < .01). The fine particle doses of all 3
products were significantly different: 21 (5) MUg of albuterol sulfate for
Ventolin, 40 (4) MUg of albuterol sulfate for Proventil, and 64 (7) MUg of
albuterol sulfate for ProAir (P < .001 for all 3 cases). The VHC successfully
removed the larger particle dose delivered by all 3 products (P <= .01) without
reducing the fine particle dose (P > .05). CONCLUSION: Ventolin, Proventil, and
ProAir should not be considered interchangeable products. In this study, the dose
of albuterol sulfate likely to reach the lungs with Proventil or ProAir is 2 to 3
times that of Ventolin. As such, patients with asthma may require 3 additional
puffs of Ventolin to achieve a clinical benefit similar to Proventil or ProAir.
Because all 3 products contain 200 actuations, it also follows that Proventil or
ProAir products may last a user 2 to 3 times longer than Ventolin.
PMID- 27613458
TI - Exploring asthma control cutoffs and economic outcomes using the Asthma Control
Questionnaire.
AB - BACKGROUND: Understanding the effect of worsening asthma control on expenditures
and health resource utilization (HRU) is important. OBJECTIVE: To explore the
association of economic outcomes with asthma control cutoffs and longitudinal
changes on the Asthma Control Questionnaire 5 (ACQ-5). METHODS: The Observational
Study of Asthma Control and Outcomes was a survey of patients with persistent
asthma who were patients of Kaiser Colorado, including claims-based HRU. Patients
completed the ACQ-5 three times during 1 year between April 2011 and June 2012.
The ACQ-5 cutoffs that indicated control were assessed in cross-sectional
analyses. Longitudinal changes in control were explored: controlled (ACQ-5 score
<0.75), indeterminate (ACQ-5 score 0.75 to <1.5), not well controlled (ACQ-5
score 1.5 to <3.0), and very poorly controlled (ACQ-5 score >=3.0). Analyses used
generalized linear models with log link (expenditures) and negative binomial
regression (HRU). RESULTS: There were 6,666 completed surveys (1,799 individuals
completed all 3 survey waves). In the cross-sectional analyses, compared with an
ACQ-5 score less than 0.5, individuals with ACQ-5 scores of 4 to 4.5 incurred 7.2
times the number of oral corticosteroid prescriptions, 4.3 times the number of
emergency department visits, 6 times the number of inpatient visits, 10.4 times
the number of asthma-specific emergency department visits, 4.58 times the number
of asthma-specific inpatient visits, and $2,892 more in all-cause and $1,877 in
asthma-specific expenditures during 4 months. In the longitudinal change
analyses, individuals who improved from an ACQ-5 of 3.0 or greater to less than
0.75 incurred $6,023 less in asthma-specific expenditures during 4 months than
those remaining at an ACQ-5 score of 3.0 or higher. CONCLUSION: Results provide
preliminary economic data on possible control cutoffs for the ACQ-5. Improving
asthma control over time may result in significant savings that may justify
financial investments designed to improve control.
PMID- 27613459
TI - Influence of health literacy and trust in online information on food allergy
quality of life and self-efficacy.
AB - BACKGROUND: Health literacy among caregivers of food allergic individuals (FAIs)
is poorly described, as are the information sources sought regarding food
allergy. OBJECTIVE: To assess the association among health literacy, trust in
online sources of information, and food allergy quality of life (QoL) and self
efficacy. METHODS: An online survey was administered to caregivers of FAIs
assessing health literacy (Newest Vital Sign [NVS] and the eHeals Internet health
literacy index), trust in online information (Hargittai Internet credibility
index and Annenberg National Health Communication Survey [ANHCS]), QoL (Food
Allergy Quality of Life Parental Burden), and self-efficacy (Food Allergy Self
Efficacy Questionnaire [FASEQ]). RESULTS: Among 1562 respondents, 94.6% (NVS) and
61.1% (eHeals) had good health literacy, and 58% had high levels of trust in
online information (both indexes). The NVS correlated poorly with the eHeals and
Hargittai indexes. Hargittai and eHeals scores were moderately correlated (r =
0.37, P < .001). A high NVS score was significantly associated with reported
anaphylaxis and high eHeals and Hargittai scores with advocacy group membership.
In unadjusted analyses, FAQL-PB scores were worse with high Hargiatti scores (P =
.05) and ANHCS scores (P < .001). The FASEQ scores were better with high ANHCS
scores (P = .02) and eHeals scores (P < .001). In an adjusted regression, high
trust in online information (both indexes), worsening FASEQ score, blog
readership, advocacy group membership, caring for multiple FAIs, and having milk
or egg allergy were associated with worse FAQL-PB scores. CONCLUSION: In this
sample, health literacy and trust in online information sources were high, with
high trust in online information sources negatively associated with QoL. Advocacy
group membership had an independent negative association with QoL.
PMID- 27613460
TI - Prevalence of fish and shellfish allergy: A systematic review.
AB - BACKGROUND: Accurate information on the prevalence of food allergy facilitates a
more evidence-based approach to planning of allergy services and can identify
important geographic variations. OBJECTIVE: To conduct a systematic review to
assess the age-specific prevalence of fish and shellfish allergy worldwide.
METHODS: Searches were conducted using Web of Science and PubMed. Population
based cross-sectional studies and cohort studies that examined the prevalence of
fish and shellfish allergy (IgE mediated and non-IgE mediated) at an identifiable
point in time were eligible for inclusion in the study. Reviewers extracted
general study information and study design, type of food allergy considered,
food(s) assessed, method of diagnosis, sampling strategy, and sample
characteristics. Raw data were extracted and percentage prevalence and 95%
confidence intervals calculated. RESULTS: A total of 7,333 articles were
identified of which 61 studies met the inclusion criteria and were included in
this review. The prevalence of fish allergy ranged from 0% to 7% and the
prevalence of shellfish allergy from 0% to 10.3%, depending on the method of
diagnosis. Where food challenges were used, the prevalence for fish allergy was
found to be 0% to 0.3% and for shellfish allergy was 0% to 0.9%. CONCLUSION: Few
studies have established the prevalence of fish or shellfish allergy using the
gold standard double-blind, placebo-controlled challenge criteria, with most
instead relying on self-reported questionnaire-based methods. The limited data
available suggest that fish allergy prevalence is similar worldwide; however,
shellfish allergy prevalence may be higher in the Southeast Asia region.
PMID- 27613461
TI - Allergy test outcomes in patients self-reported as having penicillin allergy: Two
year experience.
AB - BACKGROUND: Penicillin allergy is associated with increased antibiotic resistance
and health care costs. However, most patients with self-reported penicillin
allergy are not truly allergic. OBJECTIVE: To summarize our experience with
allergy tests in patients with a history of penicillin allergy and to compare
them with the results of other groups. METHODS: We retrospectively reviewed all
patients with a suspected clinical history of penicillin allergy referred to the
Drug Allergy Unit at University College London Hospital between March 2013 and
June 2015. RESULTS: In total, 84 patients were reviewed. The index drugs
included: unidentified penicillin (n = 44), amoxicillin (n = 17), amoxicillin
clavulanic acid (n = 13), flucloxacillin (n = 4), and other penicillins
(ampicillin, benzylpenicillin, piperacillin-tazobactam; n = 7). Allergy diagnoses
were confirmed in 24 patients (28.6%) (16 to penicillin, 3 to flucloxacillin, 5
to clavulanic acid). Twenty-two patients (91.7%) had allergy diagnosed by
positive skin test results. Two patients (8.3%) developed IgE-mediated allergic
symptoms during oral challenge (although the skin test results were negative). In
vitro specific IgE test results for penicilloyl V, penicilloyl G, and
amoxicilloyl were positive in 3 of 16 patients (18.8%). Moreover, reactions to
cefuroxime were observed in 3 of 15 patients with penicillin allergy (20%).
Selective clavulanic acid and flucloxacillin responders tolerated amoxicillin
challenge. The interval between the index reaction and evaluation was shorter (P
< .001), and the proportion of patients who could recall the name of the culprit
drug was higher (P = .009) in the allergic group. Furthermore, histories of
anaphylaxis (33.3%), urticaria, and/or angioedema (58.3%) were more common in the
allergic group. Unspecified rashes (35.0%) and nonspecific symptoms (28.3%)
predominated in the nonallergic group. CONCLUSION: Only 28.6% of patients with
self-reported penicillin allergy were confirmed to be allergic. Importantly, when
the index drug is amoxicillin-clavulanic acid or flucloxacillin, the patients may
tolerate amoxicillin.
PMID- 27613462
TI - Chronic granulomatous disease as an SOS call for multicenter cooperative effort
to prevent infections: A meta-analysis of the treatments.
AB - BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary
immunodeficiency disease. Patients with CGD experience recurrent life-threatening
infections. Lack of large interventional trials generated several doubts for the
treatment of infections in CGD. OBJECTIVE: To evaluate the effect of interferon
gamma, antifungal drugs, and antibiotics in patients with CGD undergoing
prophylaxis of infections. METHODS: A meta-analysis of the interventional trials
was performed. The studies were identified by searching MEDLINE, ISI Web of
Science, SCOPUS, and Cochrane database. The last search was run on January 2016.
Reference lists of all studies included in the present systematic review were
screened for potential additional eligible studies. RESULTS: Two studies with 163
patients with CGD were included in the interferon gamma analysis. Severe
infections occurred in 17 of 73 patients (23%) treated with interferon gamma and
in 49 of 90 patients (54%) not undergoing treatment with interferon gamma.
Compared with control, severe infections were significantly reduced in patients
treated with interferon gamma (relative risk, 0.46; 95% confidence interval, 0.29
0.73; P = .001). Interferon gamma treatment was associated with an absolute risk
reduction of 31% and a number needed to treat of 3. Furthermore, compared with
control, interferon gamma treatment reduced pulmonary infections (relative risk,
0.43; 95% confidence interval, 0.19-0.96; P = .04). Two studies with 172 patients
with CGD were included in the antifungal drug analysis. Infections occurred in 4
of 69 patients (6%) treated with antifungals and in 17 of 103 patients (16%) not
receiving treatment with antifungals. Compared with control, Aspergillus
infections were not significantly reduced in patients treated with antifungals.
No randomized prospective clinical trials of antibacterial prophylaxis in
patients with CGD have been performed. CONCLUSION: Despite the fact that
interferon gamma prophylaxis seems to have a positive effect on severe
infections, small sample sizes preclude definite conclusions. Further trials with
interferon gamma and/or antifungal and antibiotics are necessary to optimize the
treatment of CGD.
PMID- 27613463
TI - Association of TG2 from mast cells and chronic spontaneous urticaria
pathogenesis.
AB - BACKGROUND: Mast cells and their mediators play important roles in chronic
spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed
in activated mast cells and contributes to airway inflammation in allergic
asthma. OBJECTIVE: To investigate the role of TG2 in CSU. METHODS: Patients with
CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens
were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived
human mast cells and peripheral blood-derived human mast cells were activated
with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene
C4, and cytokines, were measured in serum or supernatant from cultured mast cells
by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was
determined in skin tissues by immunofluorescence. RESULTS: TG2 activity was
significantly higher in serum samples from patients with CSU than in serum
samples from healthy controls (P < .001). Colocalization of mast cell surface
marker c-kit and TG2 was significantly increased in the lesional skin of patients
with CSU compared with that in healthy controls. The levels of histamine,
leukotriene C4, tumor necrosis factor alpha, transforming growth factor beta, and
interleukins 4, 5, and 6 were significantly higher in patients with CSU than in
healthy controls (P < .001). Serum TG2 levels had positive correlations with each
inflammatory mediator (P < .001). TG2 activity was increased in cord blood
derived human mast cells (CBMCs) and peripheral blood-derived human mast cells
activated with IgE compared with those without activation (P < .05). CONCLUSION:
Our findings suggest that TG2 expressed in and released from mast cells plays an
important role in CSU pathogenesis.
PMID- 27613464
TI - Major allergen content consistency of SQ house dust mite sublingual immunotherapy
tablets and relevance across geographic regions.
AB - BACKGROUND: Consistency in composition and potency, particularly regarding major
allergens, is crucial for the quality of extracts for allergen immunotherapy.
OBJECTIVE: To characterize the major allergen composition of house dust mite
(HDM) extracts commercially available in the United States and the SQ HDM
sublingual immunotherapy (SLIT) tablet, and to relate the composition to patient
sensitization patterns. METHODS: Der 1/Der 2 ratios were determined in 10,000-
and 30,000-AU/mL HDM extracts from 5 US companies and the SQ HDM SLIT-tablet.
Allergen content was analyzed by enzyme-linked immunosorbent assay and compared
with an in-house reference. Sensitivity toward Der p 1, Der p 2, and Der p 10 was
determined in serum from randomly selected subgroups of 220 individuals from
North American and European SQ HDM SLIT-tablet trials. RESULTS: Mean Der 1/Der 2
ratios in US HDM extracts ranged from 0.4 to 20.5. For the SQ HDM SLIT-tablet (20
batches), variability did not exceed 12% regarding content of Der f 1 (SD, 11.9%;
95% confidence interval [CI], 0.94-1.06), Der p 1 (SD, 6.1%; 95% CI, 0.97-1.03),
and combined Der 2 allergen (SD, 6.4%; 95% CI, 0.97-1.03), indicating a
consistent Der 1/Der 2 ratio. High allergen sensitivity frequencies toward Der p
1 and Der p 2 were observed regardless of geographic region. Efficacy of the SQ
HDM SLIT-tablet has been demonstrated in 5 clinical trials. CONCLUSION: The SQ
HDM SLIT-tablet has efficacy potential for a broad range of patients because it
includes a consistent 1:1 ratio of the 2 major HDM allergens to which individuals
were most frequently sensitized across geographic regions. Efficacy has been
demonstrated.
PMID- 27613465
TI - Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low
osmolar contrast media in high-risk patients.
AB - BACKGROUND: Corticosteroid prophylaxis has been widely adopted for the prevention
of acute allergic-like reactions to iodinated contrast media, but its use is
still controversial because there is no strong evidence supporting its efficacy
before administration of nonionic low osmolar contrast media (LOCM). OBJECTIVE:
To assess the outcomes of premedication in patients with previous acute allergic
like reactions to LOCM in clinical practice. METHODS: A retrospective study was
performed on 322 high-risk patients who were reexposed to LOCM after
premedication composed of antihistamines and/or systemic corticosteroids because
of a previous history of acute allergic-like reactions to LOCM. RESULTS: After
premedication, 275 patients (85.4%) did not experience any reaction, but 47
patients (14.6%) still experienced a breakthrough reaction. The premedication
rate and amount of corticosteroid administered were significantly higher in the
nonrecurrence group than in the recurrence group (P = .04 and P = .04,
respectively), and a linear trend was observed in the use of corticosteroid
premedication and the efficacy of prevention (P for trend = .02). Multivariate
binary logistic regression revealed that corticosteroid premedication was
effective in preventing recurrence (odds ratio, 0.284; 95% confidence interval,
0.103-0.784). Nonetheless, despite corticosteroid premedication, 3.4% of high
risk patients still experienced moderate to severe reactions, and 14.3% of
patients with a severe index reaction again had a severe reaction. CONCLUSION:
Premedication with corticosteroids seems to be helpful in reducing the overall
rate of recurrence of acute allergic-like reactions to LOCM in high-risk
patients, but patients with severe index reactions are still at risk of
developing severe reactions despite corticosteroid premedication.
PMID- 27613466
TI - Efficacy of the novel nasal steroid S0597 tested in an environmental exposure
unit.
AB - BACKGROUND: S0597 is a novel glucocorticosteroid that was formulated as an
intranasal spray to treat seasonal allergic rhinitis (SAR). In a previous phase 2
study, doses of 100 to 400 MUg twice daily were well tolerated and more effective
than placebo for improving nasal symptoms induced by grass pollen. OBJECTIVE: To
assess the clinical efficacy and safety of a once-daily S0597 nasal spray for
treatment of SAR induced by ragweed pollen in an environmental exposure unit
(EEU). METHODS: A single-center, phase 2, randomized, double-blind study in 222
adults with SAR and a positive skin prick test result to short ragweed.
Participants underwent ragweed pollen challenge in the EEU at the screening or
priming visit and on days 1, 7, and 14 and received 50, 200, or 400 MUg of S0597
or placebo in the evening for 13 days. The primary efficacy end point was change
in total nasal symptom score (TNSS) from baseline to day 14. RESULTS: Improvement
in TNSS from baseline to day 14 was statistically significant in all S0597 groups
compared with placebo. Least-squares mean differences in change from baseline
between active treatment and placebo were 1.18, 1.84, and 1.17 for the 50-, 200-,
and 400-MUg/d S0597 groups, respectively (P < .05). The 200-MUg group
demonstrated statistically significant improvements in all TNSS subscales
(rhinorrhea, nasal congestion, sneezing, nasal itching) compared with placebo at
days 7 and 14. CONCLUSION: Treatment with 50 to 400 MUg of S0597 once daily was
well tolerated and significantly more effective than placebo in relieving nasal
symptoms of SAR associated with ragweed pollen. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01940146.
PMID- 27613467
TI - Administering multiple cumulative allergen challenges: An alternative nasal
allergen challenge protocol for the Allergic Rhinitis-Clinical Investigator
Collaborative.
PMID- 27613468
TI - Annatto seed hypersensitivity in a pediatric patient.
PMID- 27613469
TI - Severe adverse drug reactions induced by hydrochlorothiazide: A persistent old
problem.
PMID- 27613470
TI - Omalizumab and allergen immunotherapy in a patient with asthma and inhaled
corticosteroid-induced adrenal suppression.
PMID- 27613471
TI - Erratum.
PMID- 27613472
TI - Erratum.
PMID- 27613473
TI - Erratum.
PMID- 27613474
TI - Long-term survival after burns in a Swedish population.
AB - INTRODUCTION: As widely reported, the progress in burn care during recent decades
has reduced the hospital mortality. The effect of the burns on long-term outcome
has not received so much attention, and more study is indicated. The aim of this
retrospective study was to investigate the long-time survival among patients who
had been treated for burns. METHODS: We studied 1487 patients who were discharged
alive from the Linkoping University Hospital Burn Centre during the period 1993
until the end of December 2012. We used Cox's regression analysis to study the
effect of burns on long-term survival after adjustment for different factors.
RESULTS: Age and a full-thickness burn were significantly associated with
mortality after discharge (p<0.001), whereas percentage of total body surface
area burned (TBSA %), need for mechanical ventilation, and gender were not. Less
than 1% of the patients with burns (13/1487) died within 30 days of discharge and
a total of 176/1487 (12%) died during follow-up. CONCLUSION: Age and full
thickness burns reduce the long-time survival after discharge from the Burn
Centre, whereas the effect of TBSA% and need for artificial ventilation ends with
discharge.
PMID- 27613475
TI - Feasibility of monomodal analgesia with IV alfentanil during burn dressing
changes at bedside (in spontaneously breathing non-intubated patients).
AB - INTRODUCTION: The severe pain related to repeated burn dressing changes at
bedside is often difficult to manage. However these dressings can be performed at
bedside on spontaneously breathing non-intubated patients using powerful
intravenous opioids with a quick onset and a short duration of action such as
alfentanil. The purpose of this study is to demonstrate the efficacy and safety
of the protocol which is used in our burn unit for pain control during burn
dressing changes. PATIENTS AND METHODS: Cohort study began after favorable
opinion from local ethic committee has been collected. Patient's informed consent
was collected. No fasting was required. Vital signs for patients were
continuously monitored (non-invasive blood pressure, ECG monitoring, cutaneous
oxygen saturation, respiratory rate) all over the process. Boluses of 500 (+/
250) mcg IV alfentanil were administered. A continuous infusion was added in case
of insufficient analgesia. Adverse reactions were collected and pain intensity
was measured throughout the dressing using a ten step verbal rating scale (VRS)
ranging from 0 (no pain) to 10 (worst pain conceivable). RESULTS: 100 dressings
(35 patients) were analyzed. Median age was 45 years and median burned area 10%.
We observed 3 blood pressure drops, 5 oxygen desaturations (treated with
stimulation without the necessity of ventilatory support) and one episode of
nausea. Most of the patients (87%) were totally conscious during the dressing and
13% were awakened by verbal stimulation. Median total dose of alfentanil used was
2000MUg for a median duration of 35min. Pain scores during the procedure were low
or moderate (VRS mean=2.0 and maximal VRS=5). Median satisfaction collected 2h
after the dressing was 10 on a ten step scale. CONCLUSION: Pain control with
intravenous alfentanil alone is efficient and appears safe for most burn bedside
repeated dressings in hospitalized patients. It achieves satisfactory analgesia
during and after the procedure. It is now our standard analgesic method to
provide repeated bedside dressings changes for burned patients.
PMID- 27613476
TI - Albumin administration for fluid resuscitation in burn patients: A systematic
review and meta-analysis.
AB - OBJECTIVE: The objective was to systematically review the literature summarizing
the effect on mortality of albumin compared to non-albumin solutions during the
fluid resuscitation phase of burn injured patients. DATA SOURCES: We searched
MEDLINE, EMBASE and CENTRAL and the content of two leading journals in burn care,
Burns and Journal of Burn Care and Research. STUDY SELECTION: Two reviewers
independently selected randomized controlled trials comparing albumin vs. non
albumin solutions for the acute resuscitation of patients with >20% body surface
area involvement. DATA EXTRACTION: Reviewers abstracted data independently and
assessed methodological quality of the included trials using predefined criteria.
DATA SYNTHESIS: A random effects model was used to assess mortality. We
identified 164 trials of which, 4 trials involving 140 patients met our inclusion
criteria. Overall, the methodological quality of the included trials was fair. We
did not find a significant benefit of albumin solutions as resuscitation fluid on
mortality in burn patients (relative risk (RR) 1.6; 95% confidence interval (CI),
0.63-4.08). Total volume of fluid infusion during the phase of resuscitation was
lower in patients receiving albumin containing solution -1.00ml/kg/%TBSA (total
body surface area) (95% CI, -1.42 to -0.58). CONCLUSION: The pooled estimate
demonstrated a neutral effect on mortality in burn patients resuscitated acutely
with albumin solutions. Due to limited evidence and uncertainty, an adequately
powered, high quality trial could be required to assess the impact of albumin
solutions on mortality in burn patients.
PMID- 27613477
TI - Effect of parenteral glutamine supplementation combined with enteral nutrition on
Hsp90 expression and lymphoid organ apoptosis in severely burned rats.
AB - OBJECTIVE: The aim of this study is to investigate the effects of parenteral
glutamine(GLN) supplementation combined with enteral nutrition (EN) on heat shock
protein 90(Hsp90) expression, apoptosis of lymphoid organs and circulating
lymphocytes, immunological function and survival in severely burned rats.
METHODS: Male SD rats were randomly assigned into 4 groups: a sham burn+EN+GLN
free amino acid (AA) group (n=10), a sham burn+EN+GLN group (n=10), a burn+EN+AA
group (n=10), and a burn +EN +GLN group (n=10). Two hours after a 30% total body
surface area (TBSA), full-thickness scald burn injury on the back was made, the
burned rats in two experimental groups (the burn+EN+AA group and the burn+EN +GLN
group) were fed with a conventional enteral nutrition solution by oral gavage for
7 days. Simultaneously, the rats in the burn+EN+GLN group were given 0.35g GLN/kg
body weight/day once via a tail vein injection for 7 days, whereas those in the
burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid
solution (Tyrosine) for comparison. The rats in two sham burn control groups (the
sham burn+EN+AA group and the sham burn+EN +GLN group) were treated in the same
procedure as above, except for burn injury. All rats in each of the four groups
were given 175kcal/kg body wt/day. There was isonitrogenous, isovolumic and
isocaloric intake among four groups. At the end of the 7th day after nutritional
programme were finished, all rats were anesthetized and samples were collected
for further analysis. Serum immunoglobulin quantification was conducted by ELISA.
Circulating lymphocyte numbers were counted by Coulter LH-750 Analyzer. The
percentages and apoptotic ratio of CD4 and CD8T lymphocytes in circulation were
determined by flow cytometry (FCM). The neutrophil phagocytosis index (NPI) was
examined. The GLN concentrations in plasma, thymus, spleen and skeletal muscle
were measured by high performance liquid chromatography (HPLC). The organ index
evaluation and TUNEL analysis of thymus and spleen were carried out. The
expression of Hsp90 in thymus and spleen was analyzed by western blotting.
Moreover, the survival in burned rats was observed. RESULTS: The results revealed
that parenteral GLN supplementation combined with EN significantly increased the
GLN concentrations of plasma and tissues, the serum immunoglobulin content, the
circulating lymphocyte number, the CD4/CD8 ratio, the indexes of thymus and
spleen, NPI and survival as compared with the burn+EN+AA group (p<0.05). The
expression of Hsp90 in thymus and spleen in the burn+EN+GLN group was
significantly up-regulated as compared with the burn+EN+AA group (p<0.05). The
apoptosis in circulating CD4 and CD8 lymphocytes, thymus and spleen in the
burn+EN+GLN group was significantly decreased as compared with the burn+EN+AA
group (p<0.05). CONCLUSION: The results of this study show that parenteral GLN
supplementation combined with EN may increase the GLN concentrations of plasma
and tissues, up-regulate the expression of Hsp90, attenuate apoptosis in lymphoid
organ and circulating lymphocyte, enhance the immunological function and improve
survival in severely burned rats. Clinically, therapeutic efforts at the
modulation of the immune dysfunction may contribute to a favorable outcome in
severely burned patients.
PMID- 27613478
TI - Amelioration by glycine of brain damage in neonatal rat brain following hypoxia
ischemia.
AB - BACKGROUND: Glycine protected adult brains against injury in an experimental
model of stroke, but, because the ischemic response of neonatal brains differs
from that of adult brains, we examined the neuroprotective efficacy of glycine
and associated mechanisms in an experimental model of neonatal hypoxic-ischemic
(HI) encephalopathy. METHODS: Neonatal (postnatal day 7) Wistar rats were
randomly divided into an untreated group (non-HI) and two HI groups that were
treated with left common carotid artery ligation and saline control or glycine.
After recovery, pups that received surgery were injected i.p. with saline or
glycine (800 mg/kg; optimal dose determined in pilot experiments) and were placed
in a controlled 8% O2 chamber for 120 min. Brains were harvested at various times
after return to normoxia (several hours-days after HI) for analysis of infarct
area, glial activation, cell apoptosis, and tumor necrosis factor-alpha (TNF
alpha) expression on histology and reverse transcription-polymerase chain
reaction. RESULTS: Glycine injections induced large (approx. 15-fold) but brief
(approx. 2 h) increases in cerebrospinal fluid concentrations. In particular, the
glycine group had a >70% decrease in infarct areas compared with controls at 7
days after HI. Glycine also significantly reduced astrocyte reactive
transformation, microglia activation, and terminal deoxynucleotidyl transferase
dUTP nick end labeling-positive (apoptotic) cell numbers in peri-lesional areas
at 3 days after HI, and TNF-alpha mRNA expression in the injured hemisphere at 12
and 24 h after HI. CONCLUSION: Glycine protected neonatal rat brains against HI,
in part by inhibiting TNF-alpha-induced inflammation and gliosis. Hence, systemic
glycine infusions may have clinical utility for the treatment of HI injury in
human newborns.
PMID- 27613479
TI - Matrix assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS)
in clinical microbiology.
AB - The microbiological management of patients with suspected bacterial infection
includes the identification of the pathogen and the determination of the
antibiotic susceptibility. These traditional approaches, based on the pure
culture of the microorganism, require at least 36-48h. A new method, Matrix
Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF
MS), has been recently developed to profile bacterial proteins from whole cell
extracts and obtain a bacterial fingerprint able to discriminate microorganisms
from different genera and species. By whole cell-mass spectrometry, microbial
identification can be achieved within minutes from cultured isolate, rather than
traditional phenotypic or genotypic characterizations. From the year 2009 an
explosion of applications of this technology has been observed with promising
results. Several studies have been performed and showed that MALDI-TOF represents
a reliable alternative method for rapid bacteria and fungi identification in
clinical setting. A future area of expansion is represented by the application of
MALDI-TOF technology to the antibiotic susceptibility test. In conclusion, the
revision of the literature available up to date demonstrated that MALDI-TOF MS
represents an innovative technology for the rapid and accurate identification of
bacterial and fungal isolates in clinical settings. By an earlier microbiological
diagnosis, MALDI-TOF MS contributes to a reduced mortality and hospitalization
time of the patients and consequently has a significant impact on cost savings
and public health.
PMID- 27613480
TI - Trikatu, an herbal compound ameliorates rheumatoid arthritis by the suppression
of inflammatory immune responses in rats with adjuvant-induced arthritis and on
cultured fibroblast like synoviocytes via the inhibition of the NFkappaB
signaling pathway.
AB - The present study was designed to investigate the potential therapeutic effect of
trikatu, an herbal compound and its underlying molecular mechanism in rats with
adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000
mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory
cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6,
and monocyte chemoattractant protein (MCP)-1) and downregulated the mRNA
expression levels of inflammatory mediators (TNF-alpha, IL-1beta, IL-6, IL-17,
MCP-1, receptor activator of nuclear factor kappa B ligand (RANKL),
cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS)) and
transcription factors (nuclear factor kappa B 65 (NFkB-p65) and activator protein
1 (AP-1)) in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA
rats. Consistently, the protein expression of NFkB-p65, IL-17, TNF-alpha, COX-2,
and RANKL was also dramatically reduced in cultured AIA-fibroblast like
synoviocytes and synovial tissue of AIA rats by trikatu treatment. In addition,
trikatu suppressed the expression and phosphorylation of NFkB-p65 similar to the
Bay 11-7082 (NFkB inhibitor) in cultured AIA-fibroblast like synoviocytes.
Furthermore, trikatu alleviated the histopathology of joint of arthritic rats.
Overall, these data highlights that trikatu could be a promising alternative
modality for the possible treatment of rheumatoid arthritis and other
inflammatory diseases.
PMID- 27613481
TI - Gut microbiota in the pharmacokinetics and colonic deglycosylation metabolism of
ginsenoside Rb1 in rats: Contrary effects of antimicrobials treatment and
restraint stress.
AB - Ginsenoside Rb1, an active ingredient in Panax ginseng, was widely used for its
various biological activities. To clarify the role of the gut microbiota in
pharmacokinetics and metabolism of Rb1, a comprehensive and comparative study of
colonic deglycosylation metabolism and systemic exposure of ginsenoside Rb1 in
normal rats, antimicrobials (ATMs) treated rats, and restraint stressed rats was
conducted. ATMs treated rats received oral administration of non-absorbable
antimicrobial mixtures for 7 consecutive days. Restraint stressed rats were
subjected to repeated restraint stress for a period of 2 h once daily for 7 days.
Plasma concentration dynamics, urine and fecal excretion of Rb1 and its
deglycosylation metabolites (Rd, F2, and C-K) were studied. Moreover, the in
vitro metabolism of Rb1 in fecal suspension and the fecal beta-d-glucosidase
activity were profiled. Systemic exposure of the deglycosylation metabolites of
ginsenoside Rb1 (F2, C-K) were significantly higher in restraint stressed rats,
but ATMs treated rats exhibited a decreased plasma levels of F2 and C-K, compared
with normal rats. Further studies illustrated that altered systemic Rb1 and its
deglycosylation metabolites exposure in restraint-stressed rats and ATMs treated
rats may be partially attributed to alternations in cumulative fecal excretion.
The distinguishing fecal beta-d-glucosidase, in vitro elimination of Rb1, and
formation of these deglycosylation metabolites afforded further evidence for the
in vivo data. In conclusion, the dys-regulated fecal beta-d-glucosidase activity
and deglycosylation metabolism may contribute to the altered pharmacokinetic of
ginsenoside Rb1 and its hydrolysis metabolites after ATMs treatment or restraint
stress exposure. Our results may offer valuable insights into the pharmacological
changes of bioactive ginsenosides in dys-regulated gut microbiota statue.
PMID- 27613482
TI - Silica nanoparticles induce alpha-synuclein induction and aggregation in PC12
cells.
AB - Silica nanoparticles (SiO2-NPs) are widely applied in diagnosis, imaging, and
drug delivery of central nervous diseases. Previously, we found that SiO2-NPs
enter the brain and, more specifically, the dopaminergic neurons in the striatum.
Whether SiO2-NPs have neurotoxicity and contribute to development of Parkinson's
disease (PD) remains unclear. In this study, we investigated the effect of SiO2
NPs on PC12 cells, a dopaminergic neuron-like cell line. We showed that SiO2-NPs
up-regulated alpha-synuclein expression, and N-acetyl cysteine reduced alpha
synuclein. SiO2-NPs inhibited 20S proteasome activity and decreased ubiquitin,
Parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) protein levels in the
ubiquitin-proteasome system (UPS). SiO2-NPs induced autophagy as shown by
transmission electron microscopy, and elevated LC3-II and Beclin 1 levels in PC12
cells. SiO2-NPs inhibited phosphorylation of PI3K, Akt, mTOR, and P70S6. These
data suggest that SiO2-NPs induce oxidative stress and alpha-synuclein
aggregation by inhibiting the UPS. SiO2-NPs also induce autophagy through
inhibiting PI3K-Akt-mTOR signaling, which is known to negatively regulate
autophagy. Amyloid aggregates of alpha-synuclein in dopaminergic neurons of the
midbrain are considered the hallmark of PD. Our findings indicate that SiO2-NPs
exposure induces neurotoxicity and may be a significant risk factor for the
development of PD.
PMID- 27613483
TI - Mechanism of apoptosis induction in human breast cancer MCF-7 cell by Ruviprase,
a small peptide from Daboia russelii russelii venom.
AB - Ruviprase, a 4.4 kDa peptide isolated from Daboia russelii russelii venom
demonstrated antiproliferative activity against EMT6/AR1, U-87MG, HeLa and MCF-7
cancer cells with an IC50 value of 23.0, 8.8, 5.8 and 4.0 MUg ml(-1),
respectively. However, it was nontoxic to non-cancerous human embryonic kidney
cell and human peripheral blood lymphocytes. Flow-cytometric analysis confirmed
the apoptosis induction in MCF-7 cells by Ruviprase where it induced DNA
condensation but did not cause mitotic blockage or chromosomal aberration in
treated-cells. Immunofluorescence microscopic analysis indicated Ruviprase
induced apoptosis in MCF-7 cells through p53 and p21-mediated pathways. Ruviprase
generated reactive oxygen species (ROS), altered the mitochondrial transmembrane
potential, and significantly decreased the cellular glutathione (GSH) content of
MCF-7 cells. Immunoblotting and quantitative real-time PCR (qRT-PCR) analyses
suggested that Ruviprase down-regulated the expression of anti-apoptotic protein
Bcl-2, increased cleavage of poly (ADP-ribose) polymerase (PARP) protein, and up
regulated the expression of pro-apoptotic protein Bax, as well as executer
protein caspase-7 to induced apoptosis in MCF-7 cells via intrinsic pathway. This
is the first report on the characterization of the anticancer potential of a
small, non-toxic and anticoagulant peptide purified from Russell's viper venom.
PMID- 27613484
TI - Cd2+ and Pb2+ complexation by glutathione and the phytochelatins.
AB - Phytochelatins or PCn, (gammaGlu-Cys)n-Gly, and their glutathione (GSH) precursor
are thiol-rich peptides that play an important role in heavy metal detoxification
in plants and microorganisms. Complex formation between Cd2+ and Pb2+ and GSH or
PCn (n = 2, 4 and 6) are investigated by microcalorimetry, absorption
spectrophotometry and T-jump kinetics. Complex formation with Pb2+ or Cd2+ is
exothermic, and induces ligand metal charge transfer bands in UV absorption
spectral range, which implies the formation of a coordination bond between the
metal and the thiol groups of the phytochelatins. Absorption spectra and
microcalorimetry experiments allow the determination of the affinity constants
and the stoichiometry of the complexes. We show that the three PCn interact with
Pb2+ to form the 1:1 and 2:1 M:L complexes, with similar affinity constants (log
K11Pb~4.6, log K21Pb~11.4). These affinities are independent of the number of
thiols and are, moreover, lower than those determined for complex formation with
Cd2+. On the other hand, with Cd2+, PC2-Cd, PC2-Cd2, (PC2)3-Cd2, PC4-Cd, PC4-Cd2,
PC6-Cd, (PC6)2-Cd3 and PC6-Cd3 complexes are detected. Furthermore, for PC4-Cd,
the 1:1 complex is the most stable: affinity constant (log K11Cd~7.5). Kinetic
studies indicate that complex formation between Cd2+ and GSH occurs in the ms
range; direct rate constant kobs = (6.8 +/- 0.3) 106 M-1 s-1 and reverse rate
constant k-obs = 340 +/- 210 s-1. Thus, when encapsulated in a silica matrix, PCn
can be good candidates for heavy metal detection.
PMID- 27613485
TI - The circuit-breaking algorithm for monotone systems.
AB - In earlier work, we have introduced the circuit-breaking algorithm (CBA) for the
analysis of intracellular regulation networks. This algorithm uses the network
topology to construct a one-dimensional circuit-characteristic whose zeros
correspond to the fixed points of the system. In this study, we apply the CBA to
monotone systems whose flow preserves a partial order with respect to some
orthant cone. We consider relations between stability of fixed points and the
derivative of the corresponding zeros of the circuit-characteristic. In
particular, we derive sufficient conditions for instability in case of global
asymptotic stability of the open-loop system. Furthermore, we fully characterize
stability of the fixed points if in addition the system is monotone. Combined
with the theory of monotone systems, our results are used to characterize the
long-term behavior of two models for different intracellular regulation
processes.
PMID- 27613486
TI - Approaches for the estimation of timescales in nonlinear dynamical systems:
Timescale separation in enzyme kinetics as a case study.
AB - The derivation of timescales is frequently introduced as an art form in papers
and textbooks. The best scaling techniques require the application of physical
intuition to identify dimensionless variables that are one unit order of
magnitude and small parameters, which can simplify nonlinear differential
equations. However, physical intuition requires prior knowledge of the solution
to the dynamical systems under investigation. There are problems where the
application of physical intuition is not straightforward. Therefore, it is
necessary to apply mathematical techniques to estimate scales for the separation
of timescales and simplification. In this review, we present three mathematical
techniques - determination of pairwise balances, principle of minimum
simplification and scaling by inverse rates - to scale dynamical systems with
limited prior knowledge of model behavior. We illustrate the application of these
techniques with the Michaelis-Menten reaction, which is widely studied to
introduce scaling and simplification techniques in textbooks. We show that the
pairwise balance approach, though commonly introduced as a method for
nondimensionalization, can fail to derive a separation between timescales. The
other techniques we review here can be applied to a number of dynamical systems,
where the separation of timescales can lead to the simplification of a complex
nonlinear problem.
PMID- 27613488
TI - The last of the organs.
PMID- 27613487
TI - Tenofovir disoproxil fumarate-associated hypophosphatemia as determined by
fractional excretion of filtered phosphate in HIV-infected patients.
AB - INTRODUCTION: Tenofovir disoproxil fumarate (TDF) -containing regimens have been
associated with nephrotoxicity and hypophosphatemia in HIV-infected patients. The
objective of this study was to assess the possible risk factors for
hypophosphatemia and evaluate the relationship between fractional excretion of
filtered phosphate (FePi) and hypophosphatemia in TDF users. PATIENT AND METHODS:
Patients were enrolled in a prospective cohort study between January 2011 and
December 2014. We classified experienced HIV-infected patients (individuals
maintained on antiretroviral therapy (ART) for 6 months or more) and naive
patients into 3 treatment groups: TDF-containing ART (group 1), non-TDF
containing ART (never received TDF or had not received TDF in the past 6 months;
group 2) and naive to antiretroviral therapy (group 3). Specimens from each
individual were assessed for serum phosphate, serum creatinine, urine phosphate,
and urine creatinine. Multivariable logistic regression was performed to control
for the following variables measured at baseline: eGFR, age, sex, sexual
orientation, injection drug use (IDUs), HIV-RNA viral load, and CD4 cell count.
RESULTS: The frequency of hypophosphatemia in groups 1, 2, and 3 was 20.2%, 7.2%,
and 14.6%, respectively (P = 0.002). FePi above 10% also was significantly
associated with hypophosphatemia (P = 0.003; adjusted odds ratio = 2.54).
Patients with elevated CD4 cell counts (>500 cells/MUL) exhibited a lower risk of
hypophosphatemia (P = 0.002; adjusted odds ratio = 0.35). CONCLUSIONS:
Hypophosphatemia is a multifactorial etiology; FePi was confirmed as a suggested
method to predict the risk of hypophosphatemia in TDF users. Clinical Trial
Number: TYGH103011.
PMID- 27613491
TI - Three in four are unaware of obesity link to cancer, says charity.
PMID- 27613489
TI - Response to the Response to "Does tDCS Actually Deliver DC Stimulation?"
PMID- 27613490
TI - Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors
Associated With Myelosuppression in the ALSYMPCA Trial.
AB - BACKGROUND: Myelosuppression is common in patients with progressive castration
resistant prostate cancer and bone metastases. Radium-223 prolongs overall
survival in these patients but may cause myelosuppression; understanding risk
factors will improve clinical decision making. We describe hematologic safety of
radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased
risk for hematologic toxicity. PATIENTS AND METHODS: Hematologic parameters and
adverse events were analyzed. Multivariate analyses assessing baseline risk
factors for hematologic toxicities were performed separately for radium-223 and
placebo patients. RESULTS: Nine hundred one patients received radium-223 (n =
600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the
full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus
placebo patients (6% vs. 2%). Logistic regression analyses identified significant
baseline predictors for grade 2-4 hematologic toxicities related to radium-223
treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] =
2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for
anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P
= .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia.
Neutropenia events were too few in placebo patients for a comparative analysis.
There were no significant associations between hematologic toxicities and number
of radium-223 injections received (4-6 vs. 1-3). CONCLUSION: Radium-223 has a
favorable safety profile with a low myelosuppression incidence. Understanding
baseline factors associated with myelosuppression may assist clinicians in
avoiding severe myelosuppression events with radium-223.
PMID- 27613492
TI - Ultrasonographic, endoscopic and histological appearances of the caecum in cats
presenting with chronic clinical signs of caecocolic disease.
AB - Objectives This study aimed to describe the ultrasonographic, endoscopic and
histological characteristics of the caecum and ileocaecocolic junction in cats
suffering from chronic clinical signs compatible with caecocolic disease. Methods
Cats presenting with clinical signs suggestive of a caecocolic disease were
prospectively recruited. All cats underwent an ultrasonographic examination of
the caecum, ileum, colon, ileocolic lymph nodes and local mesenteric fat, in
addition to comprehensive abdominal ultrasonography. This was followed by a
colonoscopy with a macroscopic assessment of the caecocolic mucosa; caecocolic
tissue samples were systematically collected for histologic analysis. Results
Eighteen cats were included. Eleven of 18 cats had ultrasonographic abnormalities
adjacent to the ileocaecocolic junction (lymphadenopathy, local steatitis) and
13/18 cats had abnormalities directly related to the junction (wall thickening,
loss of wall layering). Seventeen of 18 cats had at least one ultrasonographic
abnormality. Endoscopically, hyperaemia, oedema, discoloration and/or erosions
were found in all cats. Each cat was classified as having mild or moderate-to
severe lesions according to endoscopic results; no classification could be
established statistically for ultrasonographic results. The accentuation of the
dimpled pattern tended to be inversely related to the severity of endoscopic
lesion scoring. Histologically, a large proportion of cats showed typhlitis
(13/16), one had lymphoma and two were normal. All cats with typhlitis also had
colitis. There was only slight agreement between endoscopic and histological
caecal results regarding the severity of lesions. Loss of caecal wall layering on
ultrasound was found in 7/18 cats and, surprisingly, did not appear as a reliable
predictor of the severity of inflammation or of malignancy; neither did local
steatitis nor lymph node size. Conclusions and relevance Ultrasonography and
endoscopy should not be used as the sole methods to investigate the
ileocaecocolic region in cats with clinical signs suggestive of caecocolic
disease. The presence of chronic clinical signs should routinely prompt
histological biopsy.
PMID- 27613493
TI - Drug exposure and clinical effect of transdermal mirtazapine in healthy young
cats: a pilot study.
AB - Objectives The objective of this study was to measure drug exposure and clinical
effects after administration of transdermal mirtazapine (TMZ) in healthy cats.
Methods Phase I: seven healthy research cats received (1) 3.75 mg and 7.5 mg TMZ
once aurally with 48 h serum sampling (serum samples were obtained via the
jugular catheter at 0, 0.5, 1, 2, 5, 9, 12, 24, 36 and 48 h); (2) 7.5 mg TMZ and
placebo daily aurally for 6 days then 48 h serum sampling; (3) 1.88 mg
mirtazapine orally once with serum sampling at 1, 4 and 8 h. Phase II: 20 client
owned cats were enrolled in a randomized, double-blind, placebo-controlled, three
way crossover clinical effect study. Treatments consisted of 6 days of aural 7.5
mg TMZ or placebo gel at home, and 1.88 mg mirtazapine orally once in the clinic.
Owners documented appetite, rate of food ingestion, begging activity and
vocalization daily at home. On day 6, food consumed, activity and vocalization
were documented in hospital, and trough and peak serum mirtazapine levels were
obtained. Serum mirtazapine and gel concentrations were measured using liquid
chromatography/tandem mass spectrometry. Results Phase I: administration of TMZ
achieved measureable serum mirtazapine concentrations. Area under the curve0-48
of multidose 7.5 mg TMZ was significantly higher than single-dose 1.88 mg oral
mirtazapine (OMZ) ( P = 0.02). Phase II: client-owned cats administered TMZ had a
significant increase in appetite ( P = 0.003), rate of food ingestion ( P =
0.002), activity ( P = 0.002), begging ( P = 0.002) and vocalization ( P = 0.002)
at home. In hospital there was a significant increase in food ingested with both
TMZ and OMZ compared with placebo ( P <0.05). Gel concentrations ranged from 87%
119% of target dose. Conclusions and relevance TMZ 7.5 mg daily achieves
measureable serum concentrations and produces significant appetite stimulation
despite variance in compounded gel concentrations, but side effects denote a
lower dose is indicated.
PMID- 27613494
TI - Differential diagnosis of left ventricular hypertrophy: usefulness of
multimodality imaging and tissue characterization with cardiac magnetic
resonance.
AB - Differential diagnosis of asymmetrical left ventricular hypertrophy may be
challenging, particularly in patients with history of hypertension. A middle-aged
man underwent an echocardiographic examination during workup for hypertension,
which unexpectedly showed significant asymmetrical septal hypertrophy and raised
suspicion for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance
confirmed the asymmetrical hypertrophy. No myocardial late gadolinium contrast
enhancement was seen. However, precontrast T1 mapping revealed a low native
myocardial T1 value. This was highly suggestive of Anderson-Fabry disease, which
was subsequently proved with very low alpha galactosidase enzyme levels and
mutation analysis. The case illustrates clinical usefulness of multimodality
imaging and the novel tissue characterization techniques for assessment of left
ventricular hypertrophy.
PMID- 27613495
TI - Monitoring and accountability for the Pacific response to the non-communicable
diseases crisis.
AB - BACKGROUND: Non-communicable diseases (NCD) are the leading cause of premature
death and disability in the Pacific. In 2011, Pacific Forum Leaders declared "a
human, social and economic crisis" due to the significant and growing burden of
NCDs in the region. In 2013, Pacific Health Ministers' commitment to 'whole of
government' strategy prompted calls for the development of a robust, sustainable,
collaborative NCD monitoring and accountability system to track, review and
propose remedial action to ensure progress towards the NCD goals and targets. The
purpose of this paper is to describe a regional, collaborative framework for
coordination, innovation and application of NCD monitoring activities at scale,
and to show how they can strengthen accountability for action on NCDs in the
Pacific. A key component is the Dashboard for NCD Action which aims to strengthen
mutual accountability by demonstrating national and regional progress towards
agreed NCD policies and actions. DISCUSSION: The framework for the Pacific
Monitoring Alliance for NCD Action (MANA) draws together core country-level
components of NCD monitoring data (mortality, morbidity, risk factors, health
system responses, environments, and policies) and identifies key cross-cutting
issues for strengthening national and regional monitoring systems. These include:
capacity building; a regional knowledge exchange hub; innovations (monitoring
childhood obesity and food environments); and a robust regional accountability
system. The MANA framework is governed by the Heads of Health and operationalised
by a multi-agency technical Coordination Team. Alliance membership is voluntary
and non-conditional, and aims to support the 22 Pacific Island countries and
territories to improve the quality of NCD monitoring data across the region. In
establishing a common vision for NCD monitoring, the framework combines data
collected under the WHO Global Framework for NCDs with a set of action-orientated
indicators captured in a NCD Dashboard for Action. Viewing NCD monitoring as a
multi-component system and providing a robust, transparent mutual accountability
mechanism helps align agendas, roles and responsibilities of countries and
support organisations. The dashboard provides a succinct communication tool for
reporting progress on implementation of agreed policies and actions and its
flexible methodology can be easily expanded, or adapted for other regions.
PMID- 27613496
TI - Intrasellar and Suprasellar Schwannoma Misdiagnosed as Pituitary Macroadenoma: A
Case Report and Review of the Literature.
AB - BACKGROUND: Intracranial schwannomas usually arise from sensory nerves with a
predilection for the trigeminal nerve and the vestibular component of the eighth
cranial nerve (VIII). Schwannoma arising in the sella and extending into the
suprasellar region is exceedingly rare and easily misdiagnosed as pituitary
macroadenoma. Only 26 cases of intrasellar schwannomas have been reported in the
literature. CASE DESCRIPTION: A patient with an intrasellar schwannoma and
suprasellar extension was presurgically diagnosed as having pituitary
macroadenoma. Subtotal excision of the lesion was performed via an endoscopic
endonasal transsphenoidal approach. Histopathology showed schwannoma. His
symptoms improved after surgery. Magnetic resonance imaging 6 months after
surgery showed a remnant schwannoma in the sella. CONCLUSIONS: Although
schwannoma in the sellar region is rare, it remains an important differential
diagnosis because of different surgical approaches.
PMID- 27613497
TI - Coconut Model for Learning First Steps of Craniotomy Techniques and Cerebrospinal
Fluid Leak Avoidance.
AB - INTRODUCTION: Neurosurgery simulation has gained attention recently due to
changes in the medical system. First-year neurosurgical residents in low-income
countries usually perform their first craniotomy on a real subject. Development
of high-fidelity, cheap, and largely available simulators is a challenge in
residency training. An original model for the first steps of craniotomy with
cerebrospinal fluid leak avoidance practice using a coconut is described.
MATERIAL AND METHODS: The coconut is a drupe from Cocos nucifera L. (coconut
tree). The green coconut has 4 layers, and some similarity can be seen between
these layers and the human skull. The materials used in the simulation are the
same as those used in the operating room. PROCEDURE: The coconut is placed on the
head holder support with the face up. The burr holes are made until endocarp is
reached. The mesocarp is dissected, and the conductor is passed from one hole to
the other with the Gigli saw. The hook handle for the wire saw is positioned, and
the mesocarp and endocarp are cut. After sawing the 4 margins, mesocarp is
detached from endocarp. Four burr holes are made from endocarp to endosperm.
Careful dissection of the endosperm is done, avoiding liquid albumen leak. The
Gigli saw is passed through the trephine holes. Hooks are placed, and the
endocarp is cut. After cutting the 4 margins, it is dissected from the endosperm
and removed. The main goal of the procedure is to remove the endocarp without
fluid leakage. DISCUSSION: The coconut model for learning the first steps of
craniotomy and cerebrospinal fluid leak avoidance has some limitations. It is
more realistic while trying to remove the endocarp without damage to the
endosperm. It is also cheap and can be widely used in low-income countries.
However, the coconut does not have anatomic landmarks. The mesocarp makes the
model less realistic because it has fibers that make the procedure more difficult
and different from a real craniotomy. CONCLUSION: The model has a potential
pedagogic neurosurgical application for freshman residents before they perform a
real craniotomy for the first time. Further validity is necessary to confirm this
hypothesis.
PMID- 27613498
TI - Predictors of Variation in Neurosurgical Supply Costs and Outcomes Across 4904
Surgeries at a Single Institution.
AB - BACKGROUND: There is high variability in neurosurgical costs, and surgical
supplies constitute a significant portion of cost. Anecdotally, surgeons use
different supplies for various reasons, but there is little understanding of how
supply choices affect outcomes. Our goal is to evaluate the effect of patient,
procedural, and provider factors on supply cost and to determine if supply cost
is associated with patient outcomes. METHODS: We obtained patient information
(age, gender, payor, case mix index [CMI], body mass index, admission source),
procedural data (procedure type, length, date), provider information (name, case
volume), and total surgical supply cost for all inpatient neurosurgical
procedures from 2013 to 2014 at our institution (n = 4904). We created mixed
effect models to examine the effect of each factor on surgical supply cost, 30
day readmission, and 30-day mortality. RESULTS: There was significant variation
in surgical supply cost between and within procedure types. Older age, female
gender, higher CMI, routine/elective admission, longer procedure, and larger
surgeon volume were associated with higher surgical supply costs (P < 0.05).
Routine/elective admission and higher surgeon volume were associated with lower
readmission rates (odds ratio, 0.707, 0.998; P < 0.01). Only patient factors of
older age, male gender, private insurance, higher CMI, and emergency admission
were associated with higher mortality (odds ratio, 1.029, 1.700, 1.692, 1.080,
2.809). There was no association between surgical supply cost and readmission or
mortality (P = 0.307, 0.548). CONCLUSIONS: A combination of patient, procedural,
and provider factors underlie the significant variation in neurosurgical supply
costs at our institution. Surgical supply costs are not correlated with 30-day
readmission or mortality.
PMID- 27613499
TI - Grip strength is potentially an early indicator of age-related decline in mice.
AB - The hand grip test has been correlated with mobility and physical performance in
older people and has been shown to be a long-term predictor of mortality.
Implementation of new strategies for enhancing healthy aging and maintaining
independent living are dependent on predictable preclinical studies. The mouse is
used extensively as a model in these types of studies, and the paw grip strength
test is similar to the hand grip test for people in that it assesses the ability
to grip a device with the paw, is non-invasive and easy to perform, and provides
reproducible information. However, little has been reported on how grip strength
declines with increasing age in mice. This report shows that grip strength was
decreased in C57BL/6 (B6) NIA and C57BL/6*BALB/c F1 (CB6F1) NIA male mice at 12
months of age compared to 8-month-old mice, and continued a robust decline to 20
months and then 28 months of age, when the study was terminated. The decline was
not related to lean muscle mass, but extensive age-related carpal and digital
exostosis could help explain the decreased grip strength times with increasing
age. In conclusion, the grip strength test could be useful in mouse preclinical
studies to help make translational predictions on treatment strategies to enhance
healthy aging.
PMID- 27613500
TI - Erratum to: Histopathological features of bone regeneration in a canine segmental
ulnar defect model.
PMID- 27613502
TI - The effect of increasing the supply of skilled health providers on pregnancy and
birth outcomes: evidence from the midwives service scheme in Nigeria.
AB - BACKGROUND: Limited availability of skilled health providers in developing
countries is thought to be an important barrier to achieving maternal and child
health-related MDG goals. Little is known, however, about the extent to which
scaling-up supply of health providers will lead to improved pregnancy and birth
outcomes. We study the effects of the Midwives Service Scheme (MSS), a public
sector program in Nigeria that increased the supply of skilled midwives in rural
communities on pregnancy and birth outcomes. METHODS: We surveyed 7,104 women
with a birth within the preceding five years across 12 states in Nigeria and
compared changes in birth outcomes in MSS communities to changes in non-MSS
communities over the same period. RESULTS: The main measured effect of the scheme
was a 7.3-percentage point increase in antenatal care use in program clinics and
a 5-percentage point increase in overall use of antenatal care, both within the
first year of the program. We found no statistically significant effect of the
scheme on skilled birth attendance or on maternal delivery complications.
CONCLUSION: This study highlights the complexity of improving maternal and child
health outcomes in developing countries, and shows that scaling up supply of
midwives may not be sufficient on its own.
PMID- 27613503
TI - Periodontal regeneration in swine after cell injection and cell sheet
transplantation of human dental pulp stem cells following good manufacturing
practice.
AB - BACKGROUND: Periodontitis, one of the most prevalent infectious diseases in
humans, results in the destruction of tooth-supporting tissues. The purpose of
the present study is to evaluate the effect of cell injection and cell sheet
transplantation on periodontal regeneration in a swine model. METHODS: In the
present study, human dental pulp stem cells (hDPSCs) were transplanted into a
swine model for periodontal regeneration. Twelve miniature pigs were used to
generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3
mm in depth. hDPSCs were obtained for bone regeneration using cell injection or
cell sheet transplantation. After 12 weeks, clinical, radiological, and
histological assessments of regenerated periodontal tissues were performed to
compare periodontal regeneration treated with xenogeneic cell injection and cell
sheet implantation. RESULTS: Our study showed that translating hDPSCs into this
large animal model could significantly improve periodontal bone regeneration and
soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC
injection significantly improved periodontal tissue healing clinically in
comparison with the control group. The volume of regenerative bone in the hDPSC
sheet group (52.7 +/- 4.1 mm(3)) was significantly larger than in the hDPSC
injection group (32.4 +/- 5.1 mm(3)) (P < 0.05). The percentage of bone in the
periodontium in the hDPSC injection group was 12.8 +/- 4.4 %, while it was 17.4
+/- 5.3 % in the hDPSC sheet group (P < 0.05). CONCLUSION: Both hDPSC injection
and cell sheet transplantation significantly regenerated periodontal bone in
swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC
injection.
PMID- 27613504
TI - Novel colon-available triterpenoids identified in raspberry fruits exhibit
antigenotoxic activities in vitro.
AB - SCOPE: Ileostomy studies provide a unique insight into digestion of food,
allowing identification of physiologically relevant dietary phytochemicals and
their metabolites important to gut health. We previously reported the consistent
increase of components in ileal fluids of ileostomates after consumption of
raspberries with use of nontargeted LC-MSn techniques and data deconvolution
software highlighting two major unknown components (m/z 355 and 679). METHODS AND
RESULTS: In-depth LC-MSn analyses suggested that the ileal m/z 355 components
were p-coumaroyl glucarates. These compounds have not been identified previously
and were confirmed in raspberry extracts after partial purification. The major
ileal component with m/z 679 was a glycoside with an aglycone of m/z 517 and was
present as two peaks in extracts of whole puree, unseeded puree, and isolated
seeds. These components were purified using Sephadex LH20 and C18 SPE units and
identified as major, novel raspberry triterpenoid glycosides. This triterpenoid
enriched fraction (100 nM) protected against H2 O2 -induced DNA damage in both
colon cancer and normal cell lines and altered expression of cytoprotective
genes. CONCLUSION: The presence of these novel raspberry triterpenoid components
in ileal fluids indicates that they would be colon-available in vivo, so
confirmation of their anticancer bioactivities is of key physiological relevance.
PMID- 27613501
TI - A current view of perlecan in physiology and pathology: A mosaic of functions.
AB - Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in
a wide array of tissues where it regulates diverse cellular processes including
bone formation, inflammation, cardiac development, and angiogenesis. Here we
provide a contemporary review germane to the biology of perlecan encompassing its
genetic regulation as well as an analysis of its modular protein structure as it
pertains to function. As perlecan signaling from the extracellular matrix
converges on master regulators of autophagy, including AMPK and mTOR, via a
specific interaction with vascular endothelial growth factor receptor 2, we
specifically focus on the mechanism of action of perlecan in autophagy and
angiogenesis and contrast the role of endorepellin, the C-terminal fragment of
perlecan, in these cellular and morphogenic events.
PMID- 27613505
TI - Effects of varenicline on motor cortical plasticity in non-smokers with
schizophrenia.
AB - BACKGROUND: Nicotinic acetylcholine receptors (nAChR) have been implicated in the
pathophysiology of schizophrenia, and deficits in this system may contribute to
high rates of cigarette smoking in this population. nAChR stimulation may
modulate neuroplasticity, or long-term potentiation (LTP), which is a key
mediator of cognitive performance. Varenicline is a nAChR partial agonist that
may improve cognitive deficits in both smokers and non-smokers with
schizophrenia; however, the mechanism by which varenicline alters cognition in
schizophrenia remains unclear. Thus, the aim of this randomized, double-blind,
placebo-controlled, crossover study was to determine the effects of varenicline
on LTP-like plasticity indexed through transcranial magnetic stimulation (TMS) in
non-smokers with schizophrenia. METHODS: Varenicline (0.5mg BID * 5 doses) or
placebo was administered to 9 non-smokers with schizophrenia and 10 non-smoker
healthy subjects. LTP-like plasticity was induced by TMS and paired associative
stimulation (PAS) at 0.1Hz to the left motor cortex and measured every 15min for
two hours post-PAS. RESULTS: There was a significant diagnosis * medication
interaction on peak potentiation (F (3, 34)=6.04, p<0.02) and post-hoc analyses
indicated that varenicline significantly increased LTP in schizophrenia and
decreased LTP in healthy subjects. CONCLUSIONS: These preliminary findings
suggest that varenicline may produce differential effects in non-smoking
schizophrenia compared to control subjects. Given the role of LTP in learning and
memory, these observations may suggest the potential for varenicline in the
treatment of cognitive deficits in patients with schizophrenia.
PMID- 27613506
TI - Cardiometabolic risk in first-episode schizophrenia (FES) patients with the
earliest stages of both illness and antipsychotic treatment.
AB - OBJECTIVE: It is well established that schizophrenia patients have high
cardiovascular morbidity and mortality. However, the underlying risk factors in
the earliest stages of both schizophrenia illness and antipsychotics treatment
are less clear. This study aimed to characterize the metabolic features of those
patients. METHODS: We performed a retrospective cohort study in a naturalistic
setting, which included antipsychotic-naive, first-episode schizophrenia (FES)
inpatients with the baseline metabolic measurements and changes following a short
term treatment with antipsychotic drugs. RESULTS: Although prevalence of
hypertriglyceridemia, hypercholesterolemia, higher-LDL-C and hyperglycaemia in
patients with FES were much lower than those of the general population (7.5% v.s.
14.9%, 9.2% v.s. 18.4%, 8.1% v.s. 14.9%, 8.6% v.s.18.3%, respectively), lower-HDL
C in patients with FES were much more prevalent than that of the general
population (19.9% v.s. 6.4%). Despite significant metabolic risk profiles (as
such lipid abnormalities and insulin resistance) increase, mean fasting glucose
and glucosylated serum protein (GSP) were significantly decreased after the short
term (median of 23days) antipsychotics exposure, compared to baseline. There is
no significant difference of the metabolic profile change between monopharmacy
and polypharmacy. CONCLUSION: These results indicated an early-onset nature of
HDL-C abnormalities in drug-naive FES patients. Lipids metabolism risk may
develop early and quickly after antipsychotic exposure. Early monitoring is
required for the purpose of early detection and hence prevention of the initial
metabolic risk which may lead to diabetes mellitus and cardiovascular disease.
PMID- 27613508
TI - Functional deficit of the medial prefrontal cortex during emotional sentence
attribution in schizophrenia.
AB - BACKGROUND: Functional brain imaging research has already demonstrated that
patients with schizophrenia had difficulties with emotion processing, namely in
facial emotion perception and emotional prosody. However, the moderating effect
of social context and the boundary of perceptual categories of emotion
attribution remain unclear. This study investigated the neural bases of emotional
sentence attribution in schizophrenia. METHODS: Twenty-one schizophrenia patients
and 25 healthy subjects underwent an event-related functional magnetic resonance
imaging paradigm including two tasks: one to classify sentences according to
their emotional content, and the other to classify neutral sentences according to
their grammatical person. RESULTS: First, patients showed longer response times
as compared to controls only during the emotion attribution task. Second,
patients with schizophrenia showed reduction of activation in bilateral auditory
areas irrespective of the presence of emotions. Lastly, during emotional
sentences attribution, patients displayed less activation than controls in the
medial prefrontal cortex (mPFC). CONCLUSIONS: We suggest that the functional
abnormality observed in the mPFC during the emotion attribution task could
provide a biological basis for social cognition deficits in patients with
schizophrenia.
PMID- 27613507
TI - Progressive deterioration of thalamic nuclei relates to cortical network decline
in schizophrenia.
AB - Thalamic abnormalities are considered part of the complex pathophysiology of
schizophrenia, particularly the involvement of specific thalamic nuclei. The
goals of this study were to: introduce a novel atlas-based parcellation scheme
for defining various thalamic nuclei; compare their integrity in a schizophrenia
sample against healthy individuals at baseline and follow-up time points, as well
as rates of change over time; examine relationships between the nuclei and
abnormalities in known connected cortical regions; and finally, to determine if
schizophrenia-related thalamic nuclei changes relate to cognitive functioning and
clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up
study, schizophrenia (n=20) and healthy individuals (n=20) were group-matched for
age, gender, and recent-alcohol use. We used high-dimensional brain mapping to
obtain thalamic morphology, and applied a novel atlas-based method for
delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross
sectional GLMs revealed group differences in bilateral mediodorsal and anterior
nuclei, while longitudinal models revealed significant group-by-time interactions
for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest
for the pulvinar in frontal, temporal and parietal regions, followed by the
mediodorsal nucleus in frontal regions, but none in the anterior nucleus.
Thalamic measures did not correlate with cognitive and clinical scores at any
time point or longitudinally. Overall, findings revealed a pattern of persistent
progressive abnormalities in thalamic nuclei that relate to advancing cortical
decline in schizophrenia, but not with measures of behavior.
PMID- 27613509
TI - Improved individualized prediction of schizophrenia in subjects at familial high
risk, based on neuroanatomical data, schizotypal and neurocognitive features.
AB - To date, there are no reliable markers for predicting onset of schizophrenia in
individuals at high risk (HR). Substantial promise is, however, shown by a
variety of pattern classification approaches to neuroimaging data. Here, we
examined the predictive accuracy of support vector machine (SVM) in later
diagnosing schizophrenia, at a single-subject level, using a cohort of HR
individuals drawn from multiply affected families and a combination of
neuroanatomical, schizotypal and neurocognitive variables. Baseline structural
magnetic resonance imaging (MRI), schizotypal and neurocognitive data from 17 HR
subjects, who subsequently developed schizophrenia and a matched group of 17 HR
subjects who did not make the transition, yet had psychotic symptoms, were
included in the analysis. We employed recursive feature elimination (RFE), in a
nested cross-validation scheme to identify the most significant predictors of
disease transition and enhance diagnostic performance. Classification accuracy
was 94% when a self-completed measure of schizotypy, a declarative memory test
and structural MRI data were combined into a single learning algorithm; higher
than when either quantitative measure was used alone. The discriminative
neuroanatomical pattern involved gray matter volume differences in frontal,
orbito-frontal and occipital lobe regions bilaterally as well as parts of the
superior, medial temporal lobe and cerebellar regions. Our findings suggest that
an early SVM-based prediction of schizophrenia is possible and can be improved by
combining schizotypal and neurocognitive features with neuroanatomical variables.
However, our predictive model needs to be tested by classifying a new,
independent HR cohort in order to estimate its validity.
PMID- 27613510
TI - Is the tri-cellular N-acetylaspartylglutamate (NAAG) cycle related to the
etiology of schizophrenia?
PMID- 27613511
TI - Preliminary evidence that schizophrenia liability at age 15 predicts suicidal
ideation two years later.
AB - We tested artifactual and theory-based accounts of the relationship between
schizophrenia liability and suicidality. At baseline, 387 adolescents (12 to
17years) completed measures of schizotypy, hopelessness, and depressed affect.
After two years, schizotypal and non-schizotypal subsamples (n=16 and 31,
respectively) self-reported passive suicidal ideation, active ideation, and
serious ideation and action. Taxonic schizotypy predicted passive ideation
(OR=8.15, 95% CI 1.34, 49.60) even when controlling for depressed affect.
Hopelessness did not predict suicidality or moderate schizotypy-suicidality
relationships. Findings were consistent with the interpersonal theory of suicide
and contrary to the artifactual account of the association.
PMID- 27613512
TI - An investigation of cytochrome p450 (CYP) and glutathione S-transferase (GST)
isoenzyme protein expression and related interactions with phototherapy in
patients with psoriasis vulgaris.
AB - Oxidative stress may play an important role in the pathogenesis of psoriasis.
Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes.
Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We
investigated the potential effects of GST and CYP enzymes in the pathogenesis of
psoriasis. The study included 32 psoriasis patients and 22 healthy subjects.
Psoriasis patients were administered 20 sessions of narrowband ultraviolet B
phototherapy. Expressions of GST and CYP enzymes were assessed by
immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were
significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001,
and P = 0.006, respectively). Pre- and post-treatment expression was similar.
Expression of CYP1A1 and CYP2E1 was significantly higher in pre- (P = 0.003 and P
= 0.001, respectively) and post-treatment (P = 0.003 and P = 0.001, respectively)
psoriatic tissues than in control tissues. No significant differences in CYP1B1
levels between the study and control groups were detected before treatment (P >
0.05). However, CYP1B1 levels were higher in post-treatment psoriatic tissue than
in control tissue (P = 0.045). The significant increases in expression of GSTK1,
GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in
response to excessive free radical formation from activated neutrophils or
ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore,
expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in
psoriasis. These findings suggest that psoriasis is an oxidative stress
condition, although phototherapy does not affect these enzymatic systems. Further
investigation is required.
PMID- 27613514
TI - Saccharibacillus endophyticus sp. nov., an endophyte of cotton.
AB - A Gram-positive-staining, facultatively aerobic, endospore-forming bacterial
strain, isolated from the stem tissue of cotton (Gossypium hirsutum) was
subjected to a detailed taxonomic study using a polyphasic approach. Based on 16S
rRNA gene sequence similarity comparisons, strain JM-1350T grouped into the genus
Saccharibacillus, and was most closely related to the type strain of
Saccharibacillus sacchari (96.5 % 16S rRNA gene sequence similarity), followed by
the type strains of Saccharibacillus kuerlensis (96.3 %) and Saccharibacillus
deserti (95.1 %). The diagnostic diamino acid of the peptidoglycan was meso
diaminopimelic acid. The quinone system contained exclusively menaquinone MK-7.
The polar lipid (L1) profile consisted of the major lipids diphosphatidylglycerol
and phosphatidylglycerol and moderate amounts of three glycolipids and an
aminophospholipid and a polar lipid (L1). The major fatty acids were iso- and
anteiso-branched fatty acids. The genomic G+C content was 55.2 mol%. In addition,
the results of physiological and biochemical tests allowed phenotypic
differentiation of strain JM-1350T from all closely related species. Thus, strain
JM-1350T represents a novel species of the genus Saccharibacillus, for which the
name Saccharibacillus endophyticus sp. nov. is proposed. The type strain is JM
1350T (=LMG 29710T=CCM 8702T).
PMID- 27613513
TI - A missense mutation in solute carrier family 12, member 1 (SLC12A1) causes
hydrallantois in Japanese Black cattle.
AB - BACKGROUND: Hydrallantois is the excessive accumulation of fluid within the
allantoic cavity in pregnant animals and is associated with fetal mortality.
Although the incidence of hydrallantois is very low in artificial insemination
breeding programs in cattle, recently 38 cows with the phenotypic appearance of
hydrallantois were reported in a local subpopulation of Japanese Black cattle. Of
these, 33 were traced back to the same sire; however, both their parents were
reported healthy, suggesting that hydrallantois is a recessive inherited
disorder. To identify autozygous chromosome segments shared by individuals with
hydrallantois and the causative mutation in Japanese Black cattle, we performed
autozygosity mapping using single-nucleotide polymorphism (SNP) array and exome
sequencing. RESULTS: Shared haplotypes of the affected fetuses spanned 3.52 Mb on
bovine chromosome 10. Exome sequencing identified a SNP (g.62382825G > A,
p.Pro372Leu) in exon 10 of solute carrier family 12, member 1 (SLC12A1), the
genotype of which was compatible with recessive inheritance. SLC12A1 serves as a
reabsorption molecule of Na(+)-K(+)-2Cl(-) in the apical membrane of the thick
ascending limb of the loop of Henle in the kidney. We observed that the
concentration of Na(+)-Cl(-) increased in allantoic fluid of homozygous SLC12A1
(g.62382825G > A) in a hydrallantois individual. In addition, SLC12A1-positive
signals were localized at the apical membrane in the kidneys of unaffected
fetuses, whereas they were absent from the apical membrane in the kidneys of
affected fetuses. These results suggested that p.Pro372Leu affects the membrane
localization of SLC12A1, and in turn, may impair its transporter activity.
Surveillance of the risk-allele frequency revealed that the carriers were
restricted to the local subpopulation of Japanese Black cattle. Moreover, we
identified a founder individual that carried the mutation (g.62382825G > A).
CONCLUSIONS: In this study, we mapped the shared haplotypes of affected fetuses
using autozygosity mapping and identified a de novo mutation in the SLC12A1 gene
that was associated with hydrallantois in Japanese Black cattle. In kidneys of
hydrallantois-affected fetuses, the mutation in SLC12A1 impaired the apical
membrane localization of SLC12A1 and reabsorption of Na(+)-K(+)-2Cl(-) in the
thick ascending limb of the loop of Henle, leading to a defect in the
concentration of urine via the countercurrent mechanism. Consequently, the
affected fetuses exhibited polyuria that accumulated in the allantoic cavity.
Surveillance of the risk-allele frequency indicated that carriers were not
widespread throughout the Japanese Black cattle population. Moreover, we
identified the founder individual, and thus could effectively manage the disorder
in the population.
PMID- 27613515
TI - Competition, salinity, and clonal growth in native and introduced irises.
AB - PREMISE OF THE STUDY: Iris pseudacorus spread rapidly into North America after
introduction from Europe in the 1800s and now co-occurs with native I. hexagona
in freshwater Louisiana wetlands. Native irises support and interact with
multiple trophic levels, whereas I. pseudacorus is classified an invasive pest
because it grows aggressively, reduces biodiversity, and displaces native
vegetation. Salinity levels are increasing in coastal wetlands worldwide. We
examined how salt-stress affects competitive interactions between these
conspecifics. METHODS: We established a three-way full-factorial common-garden
experiment that included species (I. pseudacorus, I. hexagona), competition (no
competition, intraspecific competition, and interspecific competition), and
salinity (0, 4, 8 parts per thousand NaCl), with six replicates per treatment.
KEY RESULTS: After 18 mo, Iris pseudacorus produced much more biomass than the
native species did (F1, 92 = 71.5, P < 0.0001). Interspecific competition did not
affect the introduced iris, but biomass of the native was strongly reduced
(competition * species interaction: F2, 95 = 76.7, P = 0.002). Salinity
significantly reduced biomass of both species (F2, 92 = 21.8, P < 0.0001), with
no species * salinity interaction (F2, 84 = 1.85, P = 0.16). CONCLUSIONS: Our
results demonstrate that salt stress strongly reduced clonal reproduction in
native and introduced irises; however, the introduced iris had a competitive
advantage over the native, regardless of environmental salinity levels. Based on
patterns in clonal reproduction, the introduced iris could potentially threaten
native iris populations. We are currently investigating seed production and
mortality during competition and stress because both clonal and sexual
reproduction must be considered when predicting long-term population dynamics.
PMID- 27613516
TI - Influence of light and plant size on the reproduction and growth of small palm
tree species: Comparing two methods for measuring canopy openness.
AB - PREMISE OF THE STUDY: The reproduction and growth of large palms are influenced
by many factors, including light and plant size, but few studies have examined
smaller species (up to 2 m tall). We examined the effect of incident light and
individual size on growth rates, the probability of reproduction, and the number
of inflorescences of three small palm species and compared two methods for
estimating canopy openness. METHODS: We measured canopy openness above the crowns
of 132 adult plants and in the centers of 72 subplots (10 * 10 m) where
individuals were sampled. We also recorded individual size and the number of
leaves and inflorescences produced in two years. KEY RESULTS: Reproductive
individuals of Butia paraguayensis tend to occur in illuminated microhabitats.
Reproduction of Acrocomia emensis was correlated with stem diameter, but not with
light. Reproduction was inversely related to individual size and light in Syagrus
petraea, probably because this clonal palm invests heavily in sexual reproduction
during its younger stages and clonal activity in older stages and may be adapted
to the low-light conditions of the woodland understory. Growth was not predicted
by light or individual size. Stronger correlations were found when incident light
was measured directly above the crown, as opposed to the subplot center.
CONCLUSIONS: The influences of light on reproduction are dependent on plant life
histories, even among related and sympatric species. Light measurements directly
above individual crowns provide better understanding of the reproductive effort
rather than in subplot center.
PMID- 27613517
TI - Being the stranger: Comparing study abroad experiences of nursing students in low
and high income countries through hermeneutical phenomenology.
AB - AIM: To understand the experience of American nursing students who complete a
study abroad trip to a low-income country, Bangladesh, versus a high-income
country, the Netherlands in the development of cultural consciousness. METHODS:
Hermeneutic (interpretive) phenomenology was used to explore the journals of 44
students' experiences and reflections. RESULTS: The comprehensive understanding
of the naive and structural analysis revealed that, no matter where these
students travelled, they increased their cultural consciousness. CONCLUSIONS: We
need to revise curricula to create 'change from the familiar' experiences for all
students (many cannot afford study abroad) to move students to cultural
consciousness on their journey to cultural competency that may improve client
health outcomes.
PMID- 27613518
TI - 53BP1 depletion causes PARP inhibitor resistance in ATM-deficient breast cancer
cells.
AB - BACKGROUND: Mutations in DNA damage response factors BRCA1 and BRCA2 confer
sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors in breast and
ovarian cancers. BRCA1/BRCA2-defective tumors can exhibit resistance to PARP
inhibitors via multiple mechanisms, one of which involves loss of 53BP1.
Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM)
can also sensitize tumors to PARP inhibitors, raising the question of whether the
presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast
cancer to these inhibitors. METHODS: Cytotoxicity of PARP inhibitor and ATM
inhibitor in breast cancer cell lines was assessed by MTS, colony formation and
apoptosis assays. ShRNA lentiviral vectors were used to knockdown 53BP1
expression in breast cancer cell lines. Phospho-ATM and 53BP1 protein expressions
were determined in human breast cancer tissues by immunohistochemistry (IHC).
RESULTS: We show that inhibiting ATM increased cytotoxicity of PARP inhibitor in
triple-negative and non-triple-negative breast cancer cell lines, and depleting
the cells of 53BP1 reduced this cytotoxicity. Inhibiting ATM abrogated homologous
recombination induced by PARP inhibitor, and down-regulating 53BP1 partially
reversed this effect. Further, overall survival was significantly better in
triple-negative breast cancer patients with lower levels of phospho-ATM and
tended to be better in patients with negative 53BP1. CONCLUSION: These results
suggest that 53BP1 may be a predictor of PARP inhibitor resistance in patients
with ATM-deficient tumors.
PMID- 27613519
TI - The impact of species and cell type on the nanosafety profile of iron oxide
nanoparticles in neural cells.
AB - BACKGROUND: While nanotechnology is advancing rapidly, nanosafety tends to lag
behind since general mechanistic insights into cell-nanoparticle (NP)
interactions remain rare. To tackle this issue, standardization of nanosafety
assessment is imperative. In this regard, we believe that the cell type selection
should not be overlooked since the applicability of cell lines could be
questioned given their altered phenotype. Hence, we evaluated the impact of the
cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma
cell line, neural progenitor cell line and in neural stem cells. Acute toxicity
was evaluated for gold, silver and iron oxide (IO)NPs, and the latter were
additionally subjected to a multiparametric analysis to assess sublethal effects.
RESULTS: The stem cells and murine neuroblastoma cell line respectively showed
most and least acute cytotoxicity. Using high content imaging, we observed cell
type- and species-specific responses to the IONPs on the level of reactive oxygen
species production, calcium homeostasis, mitochondrial integrity and cell
morphology, indicating that cellular homeostasis is impaired in distinct ways.
CONCLUSIONS: Our data reveal cell type-specific toxicity profiles and demonstrate
that a single cell line or toxicity end point will not provide sufficient
information on in vitro nanosafety. We propose to identify a set of standard cell
lines for screening purposes and to select cell types for detailed nanosafety
studies based on the intended application and/or expected exposure.
PMID- 27613520
TI - Against the odds, Sri Lanka eliminates malaria.
PMID- 27613521
TI - Adjunctive everolimus therapy for treatment-resistant focal-onset seizures
associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double
blind, placebo-controlled study.
AB - BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has
been used for various benign tumours associated with tuberous sclerosis complex.
We assessed the efficacy and safety of two trough exposure concentrations of
everolimus, 3-7 ng/mL (low exposure) and 9-15 ng/mL (high exposure), compared
with placebo as adjunctive therapy for treatment-resistant focal-onset seizures
in tuberous sclerosis complex. METHODS: In this phase 3, randomised, double
blind, placebo-controlled study, eligible patients aged 2-65 years with tuberous
sclerosis complex and treatment-resistant seizures (>=16 in an 8-week baseline
phase) receiving one to three concomitant antiepileptic drugs were recruited from
99 centres across 25 countries. Participants were randomly assigned (1:1:1), via
permuted-block randomisation (block size of six) implemented by Interactive
Response Technology software, to receive placebo, low-exposure everolimus, or
high-exposure everolimus. Randomisation was stratified by age subgroup (<6 years,
6 to <12 years, 12 to <18 years, and >=18 years). Patients, investigators, site
personnel, and the sponsor's study team were masked to treatment allocation. The
starting dose of everolimus depended on age, body-surface area, and concomitant
use of cytochrome 3A4/P-glycoprotein inducers. Dose adjustments were done to
attain target trough ranges during a 6-week titration period, and as needed
during a 12-week maintenance period of core phase. Patients or their caregivers
recorded events in a seizure diary throughout the study. The primary endpoint was
change from baseline in the frequency of seizures during the maintenance period,
defined as response rate (the proportion of patients achieving >=50% reduction in
seizure frequency) and median percentage reduction in seizure frequency, in all
randomised patients. This study is registered with ClinicalTrials.gov, number
NCT01713946. FINDINGS: Between July 3, 2013, and May 29, 2015, 366 patients were
enrolled and randomly assigned to placebo (n=119), low-exposure everolimus,
(n=117), or high-exposure everolimus (n=130). The response rate was 15.1% with
placebo (95% CI 9.2-22.8; 18 patients) compared with 28.2% for low-exposure
everolimus (95% CI 20.3-37.3; 33 patients; p=0.0077) and 40.0% for high-exposure
everolimus (95% CI 31.5-49.0; 52 patients; p<0.0001). The median percentage
reduction in seizure frequency was 14.9% (95% CI 0.1-21.7) with placebo versus
29.3% with low-exposure everolimus (95% CI 18.8-41.9; p=0.0028) and 39.6% with
high-exposure everolimus (95% CI 35.0-48.7; p<0.0001). Grade 3 or 4 adverse
events occurred in 13 (11%) patients in the placebo group, 21 (18%) in the low
exposure group, and 31 (24%) in the high-exposure group. Serious adverse events
were reported in three (3%) patients who received placebo, 16 (14%) who received
low-exposure everolimus, and 18 (14%) who received high-exposure everolimus.
Adverse events led to treatment discontinuation in two (2%) patients in the
placebo group versus six (5%) in the low-exposure group and four (3%) in the high
exposure group. INTERPRETATION: Adjunctive everolimus treatment significantly
reduced seizure frequency with a tolerable safety profile compared with placebo
in patients with tuberous sclerosis complex and treatment-resistant seizures.
FUNDING: Novartis Pharmaceuticals Corporation.
PMID- 27613522
TI - Seizures in tuberous sclerosis complex: hitting the target.
PMID- 27613523
TI - Children of war: urgent action is needed to save a generation.
PMID- 27613525
TI - A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in
Multiple Large-Scale and Geographically Diverse Cohorts.
AB - INTRODUCTION: There are no validated molecular methods that prospectively
identify patients with surgically resected lung squamous cell carcinoma (SCC) at
high risk for recurrence. By focusing on the expression of genes with known
functions in development of lung SCC and prognosis, we sought to develop a robust
prognostic classifier of early-stage lung SCC. METHODS: The expression of 253
genes selected by literature search was evaluated in microarrays from 107 stage
I/II tumors. Associations with survival were evaluated by Cox regression and
Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients
with SCC, respectively. A classifier score based on multivariable Cox regression
was derived and examined in six additional publicly available data sets of stage
I/II lung SCC expression profiles (n = 358). The prognostic value of this
classifier was evaluated in meta-analysis of patients with stage I/II (n = 479)
and stage I (n = 326) lung SCC. RESULTS: Dual specificity phosphatase 6 gene
(DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome
in two independent patient cohorts. Their expression values were utilized to
develop a classifier that identified patients with stage I/II lung SCC at high
risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific
mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high
risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in
publicly available data sets of stage I/II and in meta-analysis of stage I
patients. CONCLUSIONS: We have established and validated a prognostic classifier
to inform clinical management of patients with lung SCC after surgical resection.
PMID- 27613526
TI - An Anaplastic Lymphoma Kinase Immunohistochemistry-Negative but Fluorescence In
Situ Hybridization-Positive Lung Adenocarcinoma Is Resistant to Crizotinib.
AB - INTRODUCTION: Oncogenic fusion of anaplastic lymphoma kinase (ALK) with
echinoderm microtubule associated protein like 4 protein or other partner genes
occurs in 3% to 6% of lung adenocarcinomas. Although fluorescence in situ
hybridization (FISH) is the accepted standard for detecting anaplastic lymphoma
receptor tyrosine kinase gene (ALK) gene rearrangement that gives rise to new
fusion genes, not all ALK FISH-positive patients respond to ALK inhibitor
therapies. We report here an ALK FISH-positive patient-derived xenograft (PDX)
that was nonresponsive to crizotinib therapy. METHODS: The PDX patient human lung
cancer (PHLC402) was established in NOD/SCID mice from a patient with resected
pT4N1M0 lung adenocarcinoma. ALK gene status was investigated using the standard
FISH break-apart assay, reverse-transcriptase quantitative polymerase chain
reaction, RNA sequencing and immunohistochemical assay using the 5A4 antibody.
PHLC402 was treated with crizotinib (50 mg/kg) by daily oral gavage. RESULTS: ALK
FISH assay was positive in both the primary patient tumor and PDX, which were
negative for ALK protein expression by immunohistochemical analysis. ALK fusion
product was not detected by RNA sequencing and reverse-transcriptase quantitative
polymerase chain reaction comparing the 5' and 3' ALK transcript levels.
Crizotinib treatment of PHLC402 grown in mice resulted in no tumor response.
CONCLUSION: ALK protein expression may be necessary for ALK FISH-positive lung
cancer to be responsive to ALK inhibitor therapy.
PMID- 27613524
TI - Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy:
the case for repeat application as a novel therapy for lower extremity
ulceration.
AB - An emerging treatment modality for reducing damage caused by ischaemia
reperfusion injury is ischaemic conditioning. This technique induces short
periods of ischaemia that have been found to protect against a more significant
ischaemic insult. Remote ischaemic conditioning (RIC) can be administered more
conveniently and safely, by inflation of a pneumatic blood pressure cuff to a
suprasystolic pressure on a limb. Protection is then transferred to a remote
organ via humoral and neural pathways. The diabetic state is particularly
vulnerable to ischaemia-reperfusion injury, and ischaemia is a significant cause
of many diabetic complications, including the diabetic foot. Despite this,
studies utilising ischaemic conditioning and RIC in type 2 diabetes have often
been disappointing. A newer strategy, repeat RIC, involves the repeated
application of short periods of limb ischaemia over days or weeks. It has been
demonstrated that this improves endothelial function, skin microcirculation, and
modulates the systemic inflammatory response. Repeat RIC was recently shown to be
beneficial for healing in lower extremity diabetic ulcers. This article
summarises the mechanisms of RIC, and the impact that type 2 diabetes may have
upon these, with the role of neural mechanisms in the context of diabetic
neuropathy a focus. Repeat RIC may show more promise than RIC in type 2 diabetes,
and its potential mechanisms and applications will also be explored. Considering
the high costs, rates of chronicity and serious complications resulting from
diabetic lower extremity ulceration, repeat RIC has the potential to be an
effective novel advanced therapy for this condition.
PMID- 27613528
TI - Screening for obstructive sleep apnea syndrome in patients with type 2 diabetes
mellitus: a prospective study on sensitivity of Berlin and STOP-Bang
questionnaires.
AB - BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with
Type 2 diabetes mellitus representing an additional risk factor for already
increased cardiovascular mortality. As cardiovascular diseases are the main cause
of death in this population, there is a need to identify patients with moderate
to severe OSA indicated for treatment. We aimed to evaluate the performance of
the Berlin, STOP, and STOP-Bang screening questionnaires in a population of
patients with Type 2 diabetes mellitus. METHODS: 294 consecutive patients with
Type 2 diabetes mellitus filled in the questionnaires and underwent overnight
home sleep monitoring using a type IV sleep monitor. RESULTS: Severe, moderate,
and mild OSA was found in 31 (10%), 61 (21%), and 121 (41%) patients,
respectively. The questionnaires showed a similar sensitivity and specificity for
AHI >= 15: 0.69 and 0.50 for Berlin, 0.65 and 0.49 for STOP, and 0.59 and 0.68
for STOP-Bang. However, the performance of the STOP-Bang questionnaire was
different in men vs. women, sensitivity being 0.74 vs. 0.29 (p < 0.05) and
specificity 0.56 vs. 0.82 (p < 0.05). CONCLUSIONS: Even the best-performing
Berlin questionnaire failed to identify 31% of patients with moderate to severe
OSA as being at high risk of OSA, thus preventing them from receiving a correct
diagnosis and treatment. Considering that patients with Type 2 diabetes mellitus
are at high risk of cardiovascular mortality and also have a high prevalence of
moderate to severe OSA, we find screening based on the questionnaires suboptimal
and suggest that OSA screening should be performed using home sleep monitoring
devices.
PMID- 27613529
TI - Follow-Up of Norovirus Contamination in an Oyster Production Area Linked to
Repeated Outbreaks.
AB - A production area repeatedly implicated in oyster-related gastroenteritis in
France was studied for several months over 2 years. Outbreaks and field samples
were analyzed by undertaking triplicate extractions, followed by norovirus (NoV)
detection using triplicate wells for genomic amplification. This approach allowed
us to demonstrate that some variabilities can be observed for samples with a low
level of contamination, but most samples analyzed gave reproducible results. At
the first outbreak, implicated oysters were collected at the beginning of the
contamination event, which was reflected by the higher NoV levels during the
first month of the study. During the second year, NoV concentrations in samples
implicated in outbreaks and collected from the production area were similar,
confirming the failure of the shellfish depuration process. Contamination was
detected mainly during winter-spring months, and a high prevalence of NoV GI
contamination was observed. A half-life of 18 days was calculated from NoV
concentrations detected in oysters during this study, showing a very slow
decrease of the contamination in the production area. Preventing the
contamination of coastal waters should be a priority.
PMID- 27613527
TI - A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung
Adenocarcinomas with Acquired Resistance to Erlotinib.
AB - INTRODUCTION: Resistance to EGFR tyrosine kinase inhibitors develops in patients
with EGFR-mutant lung cancers. New treatments are needed to address resistance
not mediated by EGFR T790M; preclinical evidence suggests that the Janus
kinase/signal transducers and activators of transcription signaling pathway is
important in acquired resistance to EGFR-directed therapy. METHODS: We evaluated
the toxicity and efficacy of erlotinib and ruxolitinib in patients with EGFR
mutant lung cancers with acquired resistance to erlotinib. Exosomes were analyzed
to assess changes in relevant protein expression during treatment. RESULTS: We
enrolled 22 patients: 12 patients in the phase 1 portion of the study and 10
patients in the phase 2 portion. We did not observe any dose-limiting toxicities.
The maximum tolerated dose of erlotinib was 150 mg daily and that of ruxolitinib
was 20 mg twice daily. The most frequent toxicities (any grade) were anemia,
diarrhea, and elevation of liver function test results. One partial response was
observed (5% [95% confidence interval: 0-13]). The median progression-free
survival was 2.2 months (95% confidence interval: 1.4-4.1). CONCLUSION: This is
the first study assessing the combination of EGFR and Janus kinase inhibition in
patients with EGFR-mutant lung cancers. The combination was well tolerated but
ineffective. Exosomal EGFR levels may reflect changes in tumor EGFR expression in
response to therapy.
PMID- 27613530
TI - Auditory Magnetoencephalographic Frequency-Tagged Responses Mirror the Ongoing
Segmentation Processes Underlying Statistical Learning.
AB - Humans are highly sensitive to statistical regularities in their environment.
This phenomenon, usually referred as statistical learning, is most often assessed
using post-learning behavioural measures that are limited by a lack of
sensibility and do not monitor the temporal dynamics of learning. In the present
study, we used magnetoencephalographic frequency-tagged responses to investigate
the neural sources and temporal development of the ongoing brain activity that
supports the detection of regularities embedded in auditory streams. Participants
passively listened to statistical streams in which tones were grouped as
triplets, and to random streams in which tones were randomly presented. Results
show that during exposure to statistical (vs. random) streams, tritone frequency
related responses reflecting the learning of regularities embedded in the stream
increased in the left supplementary motor area and left posterior superior
temporal sulcus (pSTS), whereas tone frequency-related responses decreased in the
right angular gyrus and right pSTS. Tritone frequency-related responses rapidly
developed to reach significance after 3 min of exposure. These results suggest
that the incidental extraction of novel regularities is subtended by a gradual
shift from rhythmic activity reflecting individual tone succession toward
rhythmic activity synchronised with triplet presentation, and that these rhythmic
processes are subtended by distinct neural sources.
PMID- 27613531
TI - Evaluating the effectiveness of a brief group cognitive behavioural therapy
intervention for perinatal depression.
AB - Little is known about the effectiveness of group cognitive behavioural therapy
(CBT) in women with perinatal depression (PND) and psychiatric comorbidities.
Thirty-four women with PND (sixty-two percent with comorbidity) completed a 9
week CBT group. Eighty percent showed a clinically significant improvement in
depressive symptoms. Meaningful gains in social support, mother-infant bonding,
and partner relationship quality were seen. Brief group CBT can be effective in
the treatment of PND in women with psychiatric comorbidities and may be a less
resource-intensive alternative to individual psychotherapy.
PMID- 27613532
TI - Classifications in Brief: The Wassel Classification for Radial Polydactyly.
PMID- 27613533
TI - Value-based Healthcare: Part 2-Addressing the Obstacles to Implementing
Integrated Practice Units for the Management of Musculoskeletal Disease.
PMID- 27613536
TI - Reflections on Biosensors 2016.
PMID- 27613535
TI - Developmental changes in the level of free and conjugated sialic acids, Neu5Ac,
Neu5Gc and KDN in different organs of pig: a LC-MS/MS quantitative analyses.
AB - Recent studies have shown a relationship between the level of the sialic acid
(Sia), N-glycolylneuraminic acid (Neu5Gc) in red meat and its risk in cancer,
cardiovascular and inflammatory diseases. Unresolved is the Sia concentration in
different organs of piglets during development. Our aim was to determine the
level of free and conjugated forms of Neu5Gc, N-acetylneuraminic acid (Neu5Ac)
and ketodeoxynonulsonic acid (Kdn) in fresh and cooked spleen, kidney, lung,
heart, liver, and skeletal muscle from 3-days-old (n = 4-8), 38-days-old (n = 10)
and adult piglets (n = 4) by LC-MS/MS. Our findings show: (1) Lung tissue from 3
days-old piglets contained the highest level of total Sia (14.6 MUmol/g protein)
compared with other organs or age groups; (2) Unexpectedly, Neu5Gc was the major
Sia in spleen (67-79 %) and adult lung (36-49 %) while free Kdn was the major Sia
in skeletal muscle. Conjugated Neu5Ac was the highest Sia in other organs (61-84
%); (3) Skeletal muscle contained the lowest concentration of Neu5Gc in fresh and
cooked meat; (4) Kdn accounted for <5 % of the total Sia in most organs; (5)
During development, the total Sia concentration showed a 44-79 % decrease in all
organs; (6) In adult piglets, the high to low rank order of total Sia was lung,
heart, spleen, kidney, liver and skeletal muscle. In conclusion, the high level
of Neu5Gc in all organs compared to skeletal muscle is a potential risk factor
suggesting that dietary consumption of organ meats should be discouraged in favor
of muscle to protect against cancer, cardiovascular and other inflammatory
diseases.
PMID- 27613534
TI - Topiramate induces acute intracellular acidification in glioblastoma.
AB - Reversal of the intracellular/extracellular pH gradient is a hallmark of
malignant tumors and is an important consideration in evaluating tumor growth
potential and the effectiveness of anticancer therapies. Glioblastoma multiforme
(GBM) brain tumors have increased expression of the carbonic anhydrase (CA)
isozymes CAII, CAIX and CAXII that contribute to the altered regulation of
intracellular pH (pHi). The anti-epileptic drug topiramate (TPM) inhibits CA
action and may acidify the tumor intracellular compartment. In-vivo detection of
acute tumor acidification could aid in cancer diagnosis and monitoring treatment
response. Chemical exchange saturation transfer (CEST) magnetic resonance imaging
(MRI) has been used to measure tissue pH. Using a recently developed CEST-MRI
method called amine/amide concentration independent detection (AACID), we have
previously shown intracellular acidification caused by single dose of lonidamine.
The current study aims to evaluate the intracellular acidification induced by a
single dose of the clinically approved drug TPM. Brain tumors were induced in
NU/NU mice by injecting 105 U87 human glioblastoma multiforme cells into the
right frontal lobe. Using a 9.4T MRI scanner AACID measurements were acquired,
before and after administration of TPM (dose: 120 mg/kg, intraperitoneal), 15 +/-
2 days after tumor cell implantation. TPM administration induced acute
intracellular acidification (average +/- SD: baseline AACID = 1.14 +/- 0.05; post
AACID = 1.19 +/- 0.05, paired ttest p = 0.02) in implanted brain tumors. In
contrast, contralateral tissue showed no change in AACID value. These results
suggest that topiramate can rapidly induce a tumor specific physiological change
detectable by AACID CEST. This pH challenge paradigm could be exploited to aid in
tumor detection and monitoring treatment response.
PMID- 27613537
TI - Guanosine prevents nitroxidative stress and recovers mitochondrial membrane
potential disruption in hippocampal slices subjected to oxygen/glucose
deprivation.
AB - Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by
ischemic events and is a promising neuroprotective agent. During an ischemic
event, nitric oxide has been reported to either cause or prevent cell death. Our
aim was to evaluate the neuroprotective effects of guanosine against oxidative
damage in hippocampal slices subjected to an in vitro ischemia model, the
oxygen/glucose deprivation (OGD) protocol. We also assessed the participation of
nitric oxide synthase (NOS) enzymes activity on the neuroprotection promoted by
guanosine. Here, we showed that guanosine prevented the increase in ROS, nitric
oxide, and peroxynitrite production induced by OGD. Moreover, guanosine prevented
the loss of mitochondrial membrane potential in hippocampal slices subjected to
OGD. Guanosine did not present an antioxidant effect per se. The protective
effects of guanosine were mimicked by inhibition of neuronal NOS, but not of
inducible NOS. The neuroprotective effect of guanosine may involve activation of
cellular mechanisms that prevent the increase in nitric oxide production,
possibly via neuronal NOS.
PMID- 27613538
TI - Posteromedially placed plates with anterior staple reinforcement are not
successful in decreasing tibial slope in opening-wedge proximal tibial osteotomy.
AB - PURPOSE: To document the effectiveness of a novel technique to decrease tibial
slope in patients who underwent a proximal opening-wedge osteotomy with an
anteriorly sloped plate placed in a posteromedial position. The hypothesis was
that posteromedial placement of an anteriorly sloped osteotomy plate with an
adjunctive anterior bone staple on the tibia would decrease, and maintain, the
tibial slope correction at a minimum of 6 months following the osteotomy.
METHODS: All patients who underwent biplanar medial opening-wedge proximal tibial
osteotomy with anterior staple augmentation to decrease sagittal plane tibial
slope were included, and data were collected prospectively and reviewed
retrospectively. Indications for decreasing tibial slope included medial
compartment osteoarthritis with at least one of the following: ACL deficiency,
posterior meniscus deficiency, or flexion contracture. Preoperative, immediate
postoperative, and 6-month postoperative radiographs were reviewed. RESULTS:
Twenty-one patients (14 males and 7 females) were included in the study with a
mean age of 36.5 years. Intrarater and interrater reliability of slope
measurements were excellent at all time points (ICC >= 0.94, ICC >= 0.85). The
osteotomy resulted in an average tibial slope decrease of 0.8 from preoperative
(n.s.). At 6-month postoperative, average slope was not significantly different
from time-zero postoperative slope (mean = +0.2 degrees ). CONCLUSIONS: The most
important finding of this study was that posteromedial placement of an anteriorly
angled osteotomy plate augmented with an anterior staple during a biplanar medial
opening-wedge proximal tibial osteotomy did not decrease sagittal plane tibial
slope. Whether a staple was effective in maintaining tibial slope from time zero
to 6 months postoperatively was unable to be assessed due to no significant
change in tibial slope from the preoperative postoperative states. The results of
this study note that current osteotomy plate designs and surgical techniques are
not effective in decreasing sagittal plane tibial slope. LEVEL OF EVIDENCE: IV.
PMID- 27613539
TI - A systematic review of the effectiveness of discharge care bundles for patients
with COPD.
AB - BACKGROUND: A COPD discharge bundle is a set of evidence-based practices aimed at
improving patient outcomes after discharge from acute care settings following an
exacerbation. We conducted a systematic review on the effectiveness of COPD
discharge bundles and summarised their individual care elements. METHODS:
Biomedical electronic databases and clinical trial registries were searched from
database inception through April 2016 to identify experimental studies evaluating
care bundles offered to patients with COPD at discharge. Random-effects meta
analyses of clinical trials data were conducted for hospital readmissions,
mortality, and quality of life (QoL). RESULTS: The review included 14 studies (5
clinical trials, 7 uncontrolled trials, and 2 interrupted time series). A total
of 26 distinct elements of care were included in the bundles of individual
studies. Evidence from four clinical trials with moderate-to-high risk of bias
showed that COPD discharge bundles reduced hospital readmissions (pooled risk
ratio (RR): 0.80; 95% CI 0.65 to 0.99). There was insufficient evidence that care
bundles influence long-term mortality (RR: 0.74; 95% CI 0.43 to 1.28; four
trials) or QoL (mean difference in St. George's Respiratory Questionnaire: 1.84;
95% CI -2.13 to 5.8). CONCLUSIONS: Discharge bundles for patients with COPD led
to fewer readmissions but did not significantly improve mortality or QoL. Future
studies should employ higher quality research methods, fully report care bundle
elements, implementation strategies and intervention fidelity to better evaluate
the effectiveness of packaging evidence-based interventions together to improve
outcomes of patients with COPD discharged from acute care settings.
PMID- 27613540
TI - The accuracy of pleural ultrasonography in diagnosing complicated parapneumonic
pleural effusions.
AB - We compared the accuracy of pleural ultrasound versus chest CT versus chest
radiograph (CXR) to determine radiographic complexity in predicting a complicated
parapneumonic effusion (CPPE) defined by pleural fluid analysis. 66 patients with
parapneumonic effusions were identified with complete data. Pleural ultrasound
had a sensitivity of 69.2% (95% CI 48.2% to 85.7%) and specificity of 90.0% (95%
CI 76.3% to 97.2%). Chest CT had a sensitivity of 76.9% (95% CI 56.3% to 91.0%)
and specificity of 65.0% (95% CI 48.3% to 79.4%). CXR had a sensitivity of 61.5%
(95% CI 40.6% to 79.8%) and specificity of 60.0% (95% CI 43.3% to 75.1%). Pleural
ultrasound appears to be a superior modality to rule in a CPPE when compared with
chest CT and CXR.
PMID- 27613541
TI - Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine
uptake in rat gliomas.
AB - PURPOSE: O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is an established tracer for
the diagnosis of brain tumors with PET. This study investigates the influence of
blood-brain barrier (BBB) permeability on 18F-FET uptake in two rat glioma models
and one human xenograft model. METHODS: F98 glioma, 9L gliosarcoma or human U87
glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats.
Thereafter, animals were divided into a control group and a group receiving
injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor
growth animals received injection of Evans blue dye (EBD) to visualize BBB
disturbance and underwent 18F-FET PET followed by autoradiography. Time activity
curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of 18F
FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of
Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD
fluorescence. The membrane gaps of blood vessel endothelial tight junctions were
measured using electron microscopy to visualize ultrastructural BBB alterations
in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way
ANOVAs. RESULTS: In Dex treated animals EBD extravasation was significantly
reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98
models (P = 0.053). In contrast, no significant differences of 18F-FET uptake
were observed between Dex treated animals and control group except a decrease of
the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of
tumor blood vessel endothelia revealed significant reduction of the cleft
diameter between endothelial cells after Dex treatment in F98 model (P = 0.010).
CONCLUSION: Despite a considerable reduction of BBB permeability in rat gliomas
after Dex treatment, no relevant changes of 18F-FET uptake were noted in this
experimental study. Thus, 18F-FET uptake in gliomas appears to be widely
independent of the permeability of the BBB.
PMID- 27613542
TI - Texture analysis of 18F-FDG PET/CT to predict tumour response and prognosis of
patients with esophageal cancer treated by chemoradiotherapy.
AB - PURPOSE: This retrospective study was done to examine whether the heterogeneity
in primary tumour F-18-fluorodeoxyglucose (18F-FDG) distribution can predict
tumour response and prognosis of patients with esophageal cancer treated by
chemoradiotherapy (CRT). METHODS: The enrolled 52 patients with esophageal cancer
underwent 18F-FDG-PET/CT studies before CRT. SUVmax, SUVmean, metabolic tumour
volume (MTV, SUV >= 2.5), total lesion glycolysis (TLG) and six heterogeneity
parameters assessed by texture analysis were obtained. Patients were classified
as responders or non-responders according to Response Evaluation Criteria in
Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were
calculated by the Kaplan-Meier method. Prognostic significance was assessed by
Cox proportional hazards analysis. RESULTS: Thirty four non-responders showed
significantly higher MTV (p = 0.006), TLG (p = 0.007), intensity variability (IV;
p = 0.003) and size-zone variability (SZV; p = 0.004) than 18 responders. The
positive and negative predictive values for non-responders were 77 % and 69 % in
MTV, 76 % and 100 % in TLG, 78 % and 67 % in IV and 78 % and 82 % in SZV,
respectively. Although PFS and OS were significantly shorter in patients with
high MTV (PFS, p = 0.018; OS, p = 0.014), TLG (PFS, p = 0.009; OS, p = 0.025), IV
(PFS, p = 0.013; OS, p = 0.007) and SZV (PFS, p = 0.010; OS, p = 0.007) at
univariate analysis, none of them was an independent factor, while lymph node
status, stage and tumour response status were independent factors at multivariate
analysis. CONCLUSION: Texture features IV and SZV, and volumetric parameters MTV
and TLG can predict tumour response, but all of them have limited value in
prediction of prognosis of patients with esophageal cancer treated by CRT.
PMID- 27613543
TI - Molecular cytogenetic characterization of two established ESFT cell lines.
AB - Ewing's sarcoma/primitive neuroectodermal tumor/Askin's tumor (Ewing's sarcoma
family of tumors: ESFT) is the most common type of malignant tumor of bone and
soft tissue in children and young adults, and morphologically is a member of a
group of small round cell tumors. We report, here, on the establishment of two
human ESFT cell lines, FU-PNET-3 and FU-PNET-4, from the iliac and the chest
wall, respectively, the cells of both cell lines were tumorigenic in
immunodeficient mice. Histologically, both original and xenograft tumors and
cultured cells were composed of small round cells with positive immunoreactivity
for CD99 and Nkx2.2. Molecular biological examination demonstrated chimeric
transcripts of EWSR1 exon 7 to FLI1 exon 6 in FU-PNET-3 cells, and EWSR1 exon 10
to FLI1 exon 6 in FU-PNET-4 cells. Cytogenetic analysis revealed chromosome
translocation t(11;22)(q24;q12) and some secondary changes in both cultured
cells. These histological, molecular biological, and cytogenetical findings
indicate ESFT in both cell lines. ESFT is well studied, but its recurrent fusion
genes are heterogeneous and its biological behaviors are unclear. The FU-PNET-3
and FU-PNET-4 cell lines have been well examined and may become useful tools for
studying the genetic and biological behavioral properties of ESFT.
PMID- 27613544
TI - Plant Secondary Metabolites as Rodent Repellents: a Systematic Review.
AB - The vast number of plant secondary metabolites (PSMs) produced by higher plants
has generated many efforts to exploit their potential for pest control. We
performed a systematic literature search to retrieve relevant publications, and
we evaluated these according to PSM groups to derive information about the
potential for developing plant-derived rodent repellents. We screened a total of
54 publications where different compounds or plants were tested regarding rodent
behavior/metabolism. In the search for widely applicable products, we recommend
multi-species systematic screening of PSMs, especially from the essential oil and
terpenoid group, as laboratory experiments have uniformly shown the strongest
effects across species. Other groups of compounds might be more suitable for the
management of species-specific or sex-specific issues, as the effects of some
compounds on particular rodent target species or sex might not be present in non
target species or in both sexes. Although plant metabolites have potential as a
tool for ecologically-based rodent management, this review demonstrates
inconsistent success across laboratory, enclosure, and field studies, which
ultimately has lead to a small number of currently registered PSM-based rodent
repellents.
PMID- 27613545
TI - [Comprehensibility of online-based patient education material in ophthalmology].
AB - BACKGROUND: Investigations have shown that the internet as a source of
information in medical issues is increasing in importance. For most patients
information delivered or supported by hospitals and universities is considered to
be the most reliable, however, the comprehensibility of available information is
often considered to be wanting. Comprehensibility scores are formulae allowing a
quantitative value for the readability of a document to be calculated. OBJECTIVE:
The purpose of this study was to assess data by analyzing the comprehensibility
of medical information published on the websites of departments for ophthalmology
of German university hospitals. We investigated and analyzed medical information
dealing with three eye diseases with potentially severe irreversible damage.
METHODS: The websites of 32 departments for ophthalmology of German university
hospitals were investigated. Information regarding cataracts, glaucoma and
retinal detachment (amotio retinae) were identified and analyzed. All information
was systematically analyzed regarding comprehensibility by using the analysis
program Text-Lab ( http://www.text-lab.de ) by calculation of five readability
scores: the Hohenheim comprehensibility index (HVI), the Amstad index, the simple
measure of gobbledygook (G-SMOG) index, the Vienna non-fictional text formula (W
STX) and the readability index (LIX). RESULTS: In 59 cases (61.46 %) useful text
information from the homepage of the institutions could be detected and analyzed.
On average the comprehensibility of the information was identified as being poor
(HVI 7.91 +/- 3.94, Amstad index 35.45 +/- 11.85, Vienna formula 11.19 +/- 1.93,
G-SMOG 9.77 +/- 1.42 and the LIX 54.53 +/- 6.67). CONCLUSION: In most of the
cases patient information material was written far above the literacy level of
the average population. It must be assumed that the presented information is
difficult to read for the majority of the patients. A critical evaluation of
accessible information material seems to be desirable and available texts should
be amended.
PMID- 27613547
TI - A decade of day-case endoscopically guided stent placement in malignant
oesophagogastric strictures.
AB - BACKGROUND: Self-expanding metal stents (SEMSs) are the palliative treatment of
choice for rapid symptomatic relief in patients with malignant dysphagia.
Increasingly endoscopically guided insertion is performed as a day case and
without the need for fluoroscopic guidance. This consecutive case series reports
11-year experience of endoscopically guided SEMS insertion in a large UK
specialist oesophagogastric unit. METHODS: Patients undergoing stent insertion
for malignant dysphagia between 2003 and 2014 were identified from a
prospectively maintained database. Data on patient demographics, tumour
characteristics, indications, technique of insertion, complications, and need for
re-intervention were abstracted and then corroborated by retrospective review of
electronic case records. RESULTS: A total of 362 patients with a median age of 76
years underwent primary SEMS insertion under endoscopic guidance. Repeat
endoscopic intervention was required in 26 patients within 30 days and 59
patients within 90 days of primary insertion, giving Kaplan-Meier estimated re
intervention rates of 7.7 % and 20.3 %, respectively. Higher tumours were
associated with need for repeat intervention (p = 0.014). The most frequent
repeat intervention was insertion of a new stent, most commonly for stent
migration or tumour overgrowth. Out of 252, 222 (88.1 %) patients referred
through a rapid access pathway were stented as day cases, and the 30-day
readmission rate in this cohort did not differ significantly from patients
stented as inpatients (p = 0.774). Three (0.8 %) patients suffered a perforation,
and there was a single procedure-related death. CONCLUSIONS: This large
consecutive case series demonstrates that endoscopically guided SEMS insertion in
malignant dysphagia can be performed efficiently as a day case with low
complication, readmission, and re-intervention rates.
PMID- 27613546
TI - The effects of proteasomal inhibition on synaptic proteostasis.
AB - Synaptic function crucially depends on uninterrupted synthesis and degradation of
synaptic proteins. While much has been learned on synaptic protein synthesis,
little is known on the routes by which synaptic proteins are degraded. Here we
systematically studied how inhibition of the ubiquitin-proteasome system (UPS)
affects the degradation rates of thousands of neuronal and synaptic proteins. We
identified a group of proteins, including several proteins related to glutamate
receptor trafficking, whose degradation rates were significantly slowed by UPS
inhibition. Unexpectedly, however, degradation rates of most synaptic proteins
were not significantly affected. Interestingly, many of the differential effects
of UPS inhibition were readily explained by a quantitative framework that
considered known metabolic turnover rates for the same proteins. In contrast to
the limited effects on protein degradation, UPS inhibition profoundly and
preferentially suppressed the synthesis of a large number of synaptic proteins.
Our findings point to the importance of the UPS in the degradation of certain
synaptic proteins, yet indicate that under basal conditions most synaptic
proteins might be degraded through alternative pathways.
PMID- 27613548
TI - Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically
applicable for patients undergoing surgical resection of primary colorectal
cancer? The Leiden MRD study.
AB - PURPOSE: Current TNM staging does not appropriately identify high-risk colorectal
cancer (CRC) patients. The aim of this study was to evaluate whether the presence
of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of
stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients
undergoing surgical resection of primary CRC provides information relevant for
disease outcome. METHODS: Patients with primary CRC (n = 125), consecutively
admitted for curative resection between 2001 and 2007, were included in the
study. All patients underwent BM aspiration before surgery. Detection of tumor
cells was performed using immunocytochemical staining for cytokeratin (CK-ICC).
The TSR was determined on diagnostic H&E stained sections of primary tumors.
RESULTS: DTCs were detected in the BM of 23/125 patients (18 %). No association
was found between BM status and overall survival (HR 0.97 (95 % CI 0.45-2.09), p
= 0.93). Also, no significant difference was found in their 5-year survival rate
(resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was
found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02-4.57,
p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and
stroma-high patients, respectively. No relation was found between the presence of
DTCs and TSR. CONCLUSIONS: Our data indicate that the presence of DTCs in the BM
of CRC patients is not associated with disease outcome. The TSR was, however,
found to be associated with a worse overall survival, which indicates that for
CRC the tumor microenvironment plays an important role in its behavior and
prognosis.
PMID- 27613549
TI - The right ventricle: interaction with the pulmonary circulation.
AB - The primary role of the right ventricle (RV) is to deliver all the blood it
receives per beat into the pulmonary circulation without causing right atrial
pressure to rise. To the extent that it also does not impede left ventricular
(LV) filling, cardiac output responsiveness to increased metabolic demand is
optimized. Since cardiac output is a function of metabolic demand of the body,
during stress and exercise states the flow to the RV can vary widely. Also,
instantaneous venous return varies widely for a constant cardiac output as
ventilatory efforts alter the dynamic pressure gradient for venous return.
Normally, blood flow varies with minimal changes in pulmonary arterial pressure.
Similarly, RV filling normally occurs with minimal increases in right atrial
pressure. When pulmonary vascular reserve is compromised RV ejection may also be
compromised, increasing right atrial pressure and limiting maximal cardiac
output. Acute increases in RV outflow resistance, as may occur with acute
pulmonary embolism, will cause acute RV dilation and, by ventricular
interdependence, markedly decreased LV diastolic compliance, rapidly spiraling to
acute cardiogenic shock and death. Treatments include reversing the causes of
pulmonary hypertension and sustaining mean arterial pressure higher than
pulmonary artery pressure to maximal RV coronary blood flow. Chronic pulmonary
hypertension induces progressive RV hypertrophy to match RV contractility to the
increased pulmonary arterial elastance. Once fully developed, RV hypertrophy is
associated with a sustained increase in right atrial pressure, impaired LV
filling, and decreased exercise tolerance. Treatment focuses on pharmacologic
therapies to selectively reduce pulmonary vasomotor tone and diuretics to
minimize excessive RV dilation. Owning to the irreversible nature of most forms
of pulmonary hypertension, when the pulmonary arterial elastance greatly exceeds
the adaptive increase in RV systolic elastance, due to RV dilation, progressive
pulmonary vascular obliteration, or both, end stage cor pulmonale ensues. If
associated with cardiogenic shock, it can effectively be treated only by
artificial ventricular support or lung transplantation. Knowing how the RV adapts
to these stresses, its sign posts, and treatment options will greatly improve the
bedside clinician's ability to diagnose and treat RV dysfunction.
PMID- 27613550
TI - Urinary pH Levels are Strongly Associated with Bladder Recurrence After
Nephroureterectomy in Upper Tract Urothelial Carcinoma Patients with a Smoking
History.
AB - PURPOSE: Aromatic amines, well-known bladder carcinogens, derived from cigarette
smoke are activated by acidic urine. We herein determined whether urinary pH
levels are associated with bladder recurrence in upper tract urothelial carcinoma
patients with a positive smoking history. METHODS: A total of 256 upper tract
urothelial carcinoma patients who were surgically treated at our institution
between 1990 and 2013 were included. Urinary pH levels were defined as the median
of at least two consecutive measurements within 1 month of surgery. RESULTS:
Ninety-six patients (37.5 %) had pH <5.5 and 160 (62.5 %) had pH >=5.5, and
urinary pH levels were identified as one of the significant predictors for
bladder recurrence in univariate but not multivariate Cox regression analysis in
overall. In patients with a positive smoking history among those without a
history of bladder tumor (N = 110), the 5-year bladder recurrence-free survival
rate was 52.5 % in patients with pH >=5.5, which was significantly higher than
that in those with pH <5.5 (25.9 %, p = 0.032). In the multivariate analysis,
urinary pH <5.5 (p = 0.022, HR; 1.86) was independently associated with bladder
recurrence. No significant difference for bladder recurrence was observed between
these two groups in patients with no smoking history among them. CONCLUSIONS:
Urinary pH <5.5 is associated with an increased risk of bladder recurrence in
upper tract urothelial carcinoma patients with a positive smoking history among
those without a history of bladder tumor. Modifications to pH for urine
alkalization may prevent bladder recurrence.
PMID- 27613551
TI - Ultrasonically Activated Shears Reduce Blood Loss without Increasing Inflammatory
Reactions in Open Distal Gastrectomy for Cancer: A Randomized Controlled Study.
AB - BACKGROUND: Previous studies regarding ultrasonically activated shears (UAS) were
performed without controlled surgical procedures or consideration of potential
thermal injury due to high temperature of active blade of UAS. The purpose of
this study was to evaluate the efficacy and safety of UAS through a comparison
with conventional monopolar electrocautery (CME) in open distal gastrectomy for
gastric cancer. METHODS: From October 2011 to November 2012, 56 gastric cancer
patients eligible for open distal gastrectomy were randomized into UAS or CME
groups. Primary endpoints were estimated blood loss (EBL) during surgery and
amount of drainage through the fifth postoperative day. Secondary endpoints were
operation time, length of hospital stay, postoperative morbidity, changes in
cytokine levels in serum, peritoneal irrigation saline, and peritoneal drainage,
and inflammatory markers of serum. (Registration-number of ClinicalTrials.gov:
NCT01971775). RESULTS: EBL was lower in the UAS group than that in the CME group
(339.8 +/- 201.2 vs. 428.6 +/- 165.8 mL, p = 0.021). However, the amount of
postoperative drainage was not significantly different between the two groups.
Although the complication rate was not different between the two groups, there
were three cases of intra-abdominal bleeding requiring transfusion only in the
CME group. Inflammatory markers from the cytokine assays and serum laboratory
tests showed no significant differences between the two groups. CONCLUSIONS: UAS
reduced EBL without increasing inflammatory reactions.
PMID- 27613553
TI - Resection of the Primary Tumor Followed by Peptide Receptor Radionuclide Therapy
as Upfront Strategy for the Treatment of G1-G2 Pancreatic Neuroendocrine Tumors
with Unresectable Liver Metastases.
AB - BACKGROUND: A low burden of disease represents an independent favorable
prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in
patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it
is not clear whether this is due to a lower diffusion of the disease or thanks to
debulking surgery. METHODS: From 1996 to 2013 those patients diagnosed with G1-G2
pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were
not deemed eligible for liver radical surgery but were eligible to receive
upfront PRRT were prospectively included in the study. Two groups of comparison
were identified: those submitted for primary tumor resection before PRRT and
those who were not. The outcome was evaluated as: objective response to PRRT
(OR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the
94 subjects, 31 were previously submitted for primary tumor resection. After
propensity score adjustments, patients who underwent surgery before PRRT showed
higher stabilization or objective responses after PRRT (p = .006), and this
translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs.
65 months; p = .011), for operated versus nonoperated patients, respectively. At
multivariate analysis, operated patients showed a statistically significantly
improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous
fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048.
CONCLUSIONS: Primary tumor resection prior to PRRT can be safely proposed in G1
G2 PNETs with diffuse liver metastases because it seems to enhance response to
PRRT and to improve significantly PFS.
PMID- 27613552
TI - Clinicopathological Features and Prognosis of Mixed-Type T1a Gastric Cancer Based
on Lauren's Classification.
AB - BACKGROUND: Recent studies have reported that mixed-type (MT) gastric cancer, as
per Lauren's classification, exhibits aggressive behavior. However, the behavior
of early gastric cancer is unclear. In this study, we addressed the influence of
mucosa-confined MT gastric cancer, according to Lauren's classification, on lymph
node metastasis (LNM) and long-term outcomes. METHODS: Among patients who
underwent gastrectomy for gastric cancer from January 2000 to December 2012, 3170
had mucosa-confined gastric cancer. According to Lauren's classification, 1449
(45.7 %), 1528 (48.2 %), and 193 (6.1 %) patients had intestinal type (IT),
diffuse type (DT), and MT cancer, respectively. Moreover, patients with MT cancer
were histologically subdivided into IT-predominant MT (3.0 %) and DT-predominant
MT (2.5 %) groups. We analyzed and compared the clinicopathological
characteristics, incidence of LNM, overall survival, and recurrence-free survival
between these groups. RESULTS: Clinicopathological characteristics showed that
mucosa-confined MT gastric cancer had larger size, deeper invasion, and more
frequent lymphovascular invasion compared with IT or DT cancers. The LNM of MT
lesions (4.7 %) was comparable with that of DT lesions (4.8 %), and multivariate
logistic regression analysis indicated that Lauren's classification was a
significant predictor for LNM (P < 0.001). However, the overall survival and
recurrence-free survival of patients with MT lesions did not differ significantly
(P = 0.506 and 0.359, respectively). CONCLUSIONS: Thus, among patients with
mucosa-confined gastric cancer, those with MT cancer as per Lauren's
classification have aggressive clinical features and a risk of LNM. Hence,
surgical treatment may be the preferred option in these patients.
PMID- 27613554
TI - Lymphadenectomy during Small Bowel Neuroendocrine Tumor Surgery: The Concept of
Skip Metastases.
AB - BACKGROUND: More than half of small bowel neuroendocrine tumors (SB-NETs) are
metastatic at diagnosis, but complete resection of the primary tumor and lymph
node (LN) is recommended by most authors. Our aim was to describe the pattern of
involved LN after an extensive LN resection. MATERIALS AND METHODS: Between July
2013 and December 2015, all consecutive patients who underwent resection of at
least one SB-NET in our European Neuroendocrine Tumor Society Center of
Excellence were prospectively included, while patients with duodenal SB-NETs were
excluded. The resection and pathological analysis of LNs were standardized using
three groups (group 1, along the small intestine; group 2, along the mesenteric
vessel; and group 3, retropancreatic and mesenteric vessel origin). RESULTS:
Twenty-eight patients with SB-NET resection were prospectively enrolled in the
study, with seven patients being excluded from the analysis because it was
impossible to divide the operative piece into nodal groups due to retractile
mesenteritis. Among the remaining 21 patients, 20 (95 %) had LNs involved; 8 (38
%) in group 1, 13 (62 %) in group 2, and 12 (57 %) in group 3. Skip metastases
were found in 14 patients (67 %): 4 (19 %) with an invasion pattern of group 3+
without group 2+, and 12 (57 %) with an invasion pattern of group 2+ or group 3+
without group 1+. CONCLUSION: As a result of skip metastases, systematic,
extensive LN resection in retropancreatic portion may be required to prevent
unresectable locoregional recurrence.
PMID- 27613555
TI - The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG): "Red wine or
white"?
PMID- 27613556
TI - Risk Stratification According to the Total Number of Factors That Meet the
Indication Criteria for Radical Lymph Node Dissection in Patients with Early
Gastric Cancer at Risk for Lymph Node Metastasis.
AB - BACKGROUND: Extended indications for endoscopic resection for early gastric
cancer (EGC) have been widely accepted. However, according to current guidelines,
additional gastrectomy with lymph node dissection (LND) is recommended for
patients proven to have potential risks of lymph node metastasis (LNM) on
histopathological findings. The aim of this study was to elucidate the risk
stratification of outcome and LNM according to the number of factors that meet
the inclusion criteria for radical LND for possible LNM (LNM risk factors) in
patients with negative endoscopic resection margin. METHODS: We enrolled 511 EGC
patients whose tumors did not meet the absolute or extended indications for
endoscopic resection, and investigated the risk stratification of prognosis and
LNM according to the total number of LNM risk factors. RESULTS: Recurrence-free
and overall survival rates were significantly higher in patients with fewer LNM
risk factors for surgical indication (p = 0.0274 and 0.0002, respectively; log
rank test), and the total number of LNM risk factors and frequency of LNM were
significantly correlated (p < 0.0001; Kruskal-Wallis test). When only one LNM
risk factor was satisfied, the LNM ratio was 0.58 % (1/173, 95 % confidence
interval 0.01-3.18). CONCLUSION: The present study suggested the possibility of
using further minimally invasive treatment strategies based on the total number
of LNM risk factors.
PMID- 27613557
TI - Impact of Location of Readmission on Outcomes After Major Cancer Surgery.
AB - BACKGROUND: The burden of readmissions after major cancer surgery is high. Prior
work suggests that one-third of readmitted patients are readmitted to a different
hospital than where the surgery was performed. The impact of this location of
readmission needs to be more thoroughly understood. METHODS: This retrospective
cohort study was performed on Surveillance, Epidemiology, and End Results (SEER)
Medicare patients with bladder, esophagus, lung, or pancreas cancer diagnosed
from 2001 to 2007 who underwent extirpative surgery and were readmitted within 90
days. Readmission location was classified as 'index' if readmission was at the
hospital where surgery was performed, or 'different' if readmission was
elsewhere. Outcomes including complications, reoperations, in-hospital mortality,
90-day mortality, and 90-day total costs were compared based on the location of
readmission using a propensity score inverse probability treatment weight
analysis. RESULTS: Overall, 7903 (28 %) patients were readmitted within 90 days
of index hospitalization. Thirty-three percent were readmitted to a different
hospital (bladder 30 %, esophagus 34 %, lung 34 %, pancreas 34 %). Ninety-day
mortality and total costs of care were not significantly different between the
readmission location groups (all p > 0.05); however, substantial differences in
the types of patients, and timing of and reasons for readmission were observed
between the two groups. CONCLUSIONS: Patients readmitted to different hospitals
after major cancer surgery are a different group of patients than those
readmitted to the index hospital. Accounting for this, we did not find
significant differences in short-term clinical outcomes or costs of care based on
readmission location; however, differences in long-term outcomes were observed
that should be further explored in future studies.
PMID- 27613558
TI - Variation in Hospital-Specific Rates of Suboptimal Lymphadenectomy and Survival
in Colon Cancer: Evidence from the National Cancer Data Base.
AB - BACKGROUND: Little is known about between-hospital differences in the rate of
suboptimal lymphadenectomy. This study characterizes variation in hospital
specific rates of suboptimal lymphadenectomy and its effect on overall survival
in a national hospital-based registry. METHODS: Stage I-III colon cancer patients
were identified from the 2003-2012 National Cancer Data Base. Bayesian multilevel
logistic regression models were used to assess the impact of patient- and
hospital-level factors on hospital-specific rates of suboptimal lymphadenectomy
(<12 lymph nodes), and multilevel Cox models were used to estimate the effect of
suboptimal lymphadenectomy at the patient (yes vs. no) and hospital level
(quartiles of hospital-specific rates) on overall survival. RESULTS: A total of
360,846 patients across 1345 hospitals in the US met the inclusion criteria, of
which 25 % had a suboptimal lymphadenectomy. Wide variation was observed in
hospital-specific rates of suboptimal lymphadenectomy (range 0-82 %, median 44
%). Older age, male sex, comorbidity score, no insurance, positive margins, lower
tumor grade, lower T and N stage, and sigmoid and left colectomy were associated
with higher odds of suboptimal lymphadenectomy. Patients treated at lower-volume
and non-academic hospitals had higher odds of suboptimal lymphadenectomy. Patient
and hospital-level factors explained 5 % of the between-hospital variability in
suboptimal lymphadenectomy, leaving 95 % unexplained. Higher suboptimal
lymphadenectomy rates were associated with worse survival (quartile 4 vs.
quartile 1: hazard ratio 1.19, 95 % confidence interval 1.16-1.22). CONCLUSION:
Large differences in hospital-specific rates of suboptimal lymphadenectomy were
observed, and this variation was associated with survival. Quality improvement
initiatives targeting hospital-level adherence to the national standard may
improve overall survival among resected colon cancer patients.
PMID- 27613560
TI - Placebo controls in clinical trials: concerns about use in relapse prevention
studies in schizophrenia.
PMID- 27613559
TI - The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell
Carcinoma with Partial or Complete Response After Radical Chemo-Intensity
Modulated Radiotherapy (IMRT).
AB - BACKGROUND: This study investigated the therapeutic benefit of radical resection
(SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or
complete response after radical chemoradiotherapy (CRT). METHODS: At the authors'
institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were
treated with CRT from January 2009 to December 2014. All of them were irradiated
using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy;
range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or
complete response after CRT, 33 were treated further with SRR and 32 with
adjuvant chemotherapy or observation. The locoregional control (LRC), overall
survival (OS), and cancer-free survival (CFS) rates were compared between the two
groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1,
and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR
group (p < 0.05). Multivariate analysis showed that SRR was the only
statistically significant prognostic factor related to LRC, OS, and CFS. For
those with SRR, pathologic downstaging was observed in 27 cases (81.8 %).
Perioperative flap failure was observed in three cases (9.2 %) and neck wound
necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in
the therapy is technically safe and has survival benefit, with a significant
response after CRT applied by IMRT, with a radical dose in the gross tumor area.
PMID- 27613561
TI - Influence of occupation on lumbar spine degeneration in men: the Korean National
Health and Nutrition Examination Survey 2010-2013.
AB - PURPOSE: Certain lifetime occupations can influence lumbar spine degeneration
(LSD). The authors investigated the association between various types of
occupations and LSD using a nationwide survey. METHODS: Data were obtained from
the 2010 to 2013 Korea National Health and Nutrition Examination Survey
(KNHANES). Types of lifetime occupation were categorized into four occupational
groups: white-collar (WC) workers, pink-collar (PC) workers, blue-collar (BC)
workers, and agribusiness and low-level (AL) workers. LSD was evaluated using a
modified version of the Kellgren-Lawrence grade. RESULTS: The results showed that
the type of occupation was associated with increased risk of LSD. The risk of LSD
increased in BC workers (adjusted OR 1.492; 95 % CI 1.13, 1.98) and AL workers
(adjusted OR 2.539; 95 % CI 1.75, 3.68). The risk of severe LSD increased in BC
workers (adjusted OR 1.734; 95 % CI 0.78, 1.98) and AL workers (adjusted OR
3.058; 95 % CI 1.96, 4.77). The risk of LBP tended to increase in AL workers
(adjusted OR 1.380; 95 % CI 1.00, 1.90). CONCLUSIONS: Our results suggest that
LSD is influenced by the lifetime occupation: WC workers are least affected by
LSD, and AL workers are at greatest risk of LSD.
PMID- 27613563
TI - Does Lipid Profile Affect Thrombin Generation During Ramadan Fasting in Patients
With Cardiovascular Risks?
AB - There is evidence that diet and variation in lipid metabolism can influence blood
coagulation, but little is known about the effect of Ramadan fasting on plasmatic
coagulation pattern. We investigated the effect of Ramadan fasting on thrombin
generation (TG) in patients with cardiovascular disease (CVD) risks, and we aimed
to assess the effect of lipid profile on TG parameters. The study was conducted
in 36 adults having at least 2 CVD risks and in 30 healthy controls. Coagulation
pattern was assessed by both classical clotting times and TG test. A complete
lipid profile was performed simultaneously. Patients were invited 2 times: 1 week
before Ramadan and during the last week of the Ramadan. The TG parameters were
not different in patients with CVD risks compared to healthy controls. Fasting
had no effect on plasmatic coagulation parameters and on TG profile. Individual
analysis of the mean rate index (MRI) of TG revealed 3 groups: group 1 with no
modification of MRI, group 2 with a significant increase in MRI (81.64 nM/min vs
136.07 nM/min; P < .001), and group 3 with a significant decrease in MRI (125.27
nM/min vs 73.18 nM/min; P = .001). Only in group 2, a significant increase was
observed in total cholesterol and low-density lipoprotein cholesterol. Changes in
lipid profile during Ramadan fasting did not influence the global coagulation
pattern in patients with CVD risks. Whereas, a significant increase in the
propagation phase of TG was associated with a significant increase in cholesterol
levels, which was not found with the other TG parameters.
PMID- 27613562
TI - Cardiovascular Disease Risk Prediction in the HIV Outpatient Study.
AB - BACKGROUND: Cardiovascular disease (CVD) risk prediction tools are often applied
to populations beyond those in which they were designed when validated tools for
specific subpopulations are unavailable. METHODS: Using data from 2283 human
immunodeficiency virus (HIV)-infected adults aged >=18 years, who were active in
the HIV Outpatient Study (HOPS), we assessed performance of 3 commonly used CVD
prediction models developed for general populations: Framingham general
cardiovascular Risk Score (FRS), American College of Cardiology/American Heart
Association Pooled Cohort equations (PCEs), and Systematic COronary Risk
Evaluation (SCORE) high-risk equation, and 1 model developed in HIV-infected
persons: the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study
equation. C-statistics assessed model discrimination and the ratio of expected to
observed events (E/O) and Hosmer-Lemeshow chi2 P value assessed calibration.
RESULTS: From January 2002 through September 2013, 195 (8.5%) HOPS participants
experienced an incident CVD event in 15 056 person-years. The FRS demonstrated
moderate discrimination and was well calibrated (C-statistic: 0.66, E/O: 1.01, P
= .89). The PCE and D:A:D risk equations demonstrated good discrimination but
were less well calibrated (C-statistics: 0.71 and 0.72 and E/O: 0.88 and 0.80,
respectively; P < .001 for both), whereas SCORE performed poorly (C-statistic:
0.59, E/O: 1.72; P = .48). CONCLUSIONS: Only the FRS accurately estimated risk
of CVD events, while PCE and D:A:D underestimated risk. Although these models
could potentially be used to rank US HIV-infected individuals at higher or lower
risk for CVD, the models may fail to identify substantial numbers of HIV-infected
persons with elevated CVD risk who could potentially benefit from additional
medical treatment.
PMID- 27613564
TI - Clinician-identified problems and solutions for delayed diagnosis in primary
care: a PRIORITIZE study.
AB - BACKGROUND: Delayed diagnosis in primary care is a common, harmful and costly
patient safety incident. Its measurement and monitoring are underdeveloped and
underutilised. We created and implemented a novel approach to identify problems
leading to and solutions for delayed diagnosis in primary care. METHODS: We
developed a novel priority-setting method for patient safety problems and
solutions called PRIORITIZE. We invited more than 500 NW London clinicians via an
open-ended questionnaire to identify three main problems and solutions relating
to delayed diagnosis in primary care. 113 clinicians submitted their suggestions
which were thematically grouped and synthesized into a composite list of 33
distinct problems and 27 solutions. A random group of 75 clinicians from the
initial cohort scored these and an overall ranking was derived. The agreement
between the clinicians' scores was presented using the Average Expert Agreement.
RESULTS: The top ranked problems were poor communication between secondary and
primary care and the inverse care law, i.e. a mismatch between patients' medical
needs and healthcare supply. The highest ranked solutions included: a more
rigorous system of communicating abnormal results of investigations to patients,
direct hotlines to specialists for GPs to discuss patient problems and better
training of primary care clinicians in relevant areas. A priority highlighted
throughout the findings is a need to improve communication between clinicians as
well as with patients. The highest ranked suggestions had the highest consensus
between experts. CONCLUSIONS: The novel method we have developed is highly
feasible, informative and scalable, and merits wider exploration with a view of
becoming part of a routine pro-active and preventative system for patient safety
assessment. Clinicians proposed a range of concrete suggestions with an emphasis
on improving communication among clinicians and with patients and better GP
training. In their view, delayed diagnosis can be largely prevented with
interventions requiring relatively minor investment. Rankings of identified
problems and solutions can serve as an aid to policy makers and commissioners of
care in prioritization of scarce healthcare resources.
PMID- 27613566
TI - hnRNP A1 antagonizes cellular senescence and senescence-associated secretory
phenotype via regulation of SIRT1 mRNA stability.
AB - Senescent cells display a senescence-associated secretory phenotype (SASP) which
contributes to tumor suppression, aging, and cancer. However, the underlying
mechanisms for SASP regulation are not fully elucidated. SIRT1, a nicotinamide
adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism,
inflammatory response, and longevity, etc. However, its posttranscriptional
regulation and its roles in cellular senescence and SASP regulation are still
elusive. Here, we identify the RNA-binding protein hnRNP A1 as a
posttranscriptional regulator of SIRT1, as well as cell senescence and SASP
regulator. hnRNP A1 directly interacts with the 3' untranslated region of SIRT1
mRNA, promotes its stability, and increases SIRT1 expression. hnRNP A1 delays
replicative cellular senescence and prevents from Ras OIS via upregulation of
SIRT1 expression to deacetylate NF-kappaB, thus blunting its transcriptional
activity and subsequent IL-6/IL-8 induction. hnRNP A1 overexpression promotes
cell transformation and tumorigenesis in a SIRT1-dependent manner. Together, our
findings unveil a novel posttranscriptional regulation of SIRT1 by hnRNP A1 and
uncover a critical role of hnRNP A1-SIRT1-NF-kappaB pathway in regulating
cellular senescence and SASP expression.
PMID- 27613567
TI - Accessibility of standardized information of a national colorectal cancer
screening program for low health literate screening invitees: A mixed method
study.
AB - OBJECTIVE: To explore the accessibility of standardized printed information
materials of the national Dutch colorectal cancer screening program among low
health literate screening invitees and to assess the effect of the information on
their knowledge about colorectal cancer and the screening program. METHODS:
Linguistic tools were used to analyze the text and design characteristics. The
accessibility, comprehensibility and relevance of the information materials were
explored in interviews and in observations (n=25). The effect of the information
on knowledge was assessed in an online survey (n=127). RESULTS: The materials
employed a simple text and design. However, respondents expressed problems with
the amount of information, and the difference between screening and diagnostic
follow-up. Knowledge significantly increased in 10 out of 16 items after reading
the information but remained low for colorectal cancer risk, sensitivity of
testing, and the voluntariness of colorectal cancer screening. CONCLUSION:
Despite intelligible linguistic and design characteristics, screening invitees
with low health literacy had problems in accessing, comprehending and applying
standard information materials on colorectal cancer screening, and lacked
essential knowledge for informed decision-making about participation. PRACTICE
IMPLICATIONS: To enable equal access to informed decision-making, information
strategies need to be adjusted to the skills of low health literate screening
invitees.
PMID- 27613568
TI - "Shedding light on a dark question": Peripheral oxytocin signalling and
neurobehavioral responses to intranasal oxytocin in humans.
PMID- 27613565
TI - The SCARE Statement: Consensus-based surgical case report guidelines.
AB - INTRODUCTION: Case reports have been a long held tradition within the surgical
literature. Reporting guidelines can improve transparency and reporting quality.
However, recent consensus-based guidelines for case reports (CARE) are not
surgically focused. Our objective was to develop surgical case report guidelines.
METHODS: The CARE statement was used as the basis for a Delphi consensus. The
Delphi questionnaire was administered via Google Forms and conducted using
standard Delphi methodology. A multidisciplinary group of surgeons and others
with expertise in the reporting of case reports were invited to participate. In
round one, participants stated how each item of the CARE statement should be
changed and what additional items were needed. Revised and additional items from
round one were put forward into a further round, where participants voted on the
extent of their agreement with each item, using a nine-point Likert scale, as
proposed by the Grading of Recommendations, Assessment, Development and
Evaluations (GRADE) working group. RESULTS: In round one, there was a 64% (38/59)
response rate. Following adjustment of the guideline with the incorporation of
recommended changes, round two commenced and there was an 83% (49/59) response
rate. All but one of the items were approved by the participants, with Likert
scores 7-9 awarded by >70% of respondents. The final guideline consists of a 14
item checklist. CONCLUSION: We present the SCARE Guideline, consisting of a 14
item checklist that will improve the reporting quality of surgical case reports.
PMID- 27613569
TI - The relationship between baseline EEG spectra power and memory performance in
older African Americans endorsing cognitive concerns in a community setting.
AB - The finding that some older individuals report declines in aspects of cognitive
functioning is becoming a frequently used criteria to identify elderly at risk
for mild cognitive impairment (MCI) and dementia. Once concerns are identified in
a community setting, however, effective means are necessary to pinpoint those
individuals who should go on to more complex and costly diagnostic evaluations
(e.g., functional imaging). We tested 44 African American volunteers endorsing
cognitive concerns (37 females, 7 males) age>=65years with CogState battery
subtests and recorded resting-state EEG, with eyes closed. After current source
density (CSD) transformations of EEG recordings we obtained spectral power for
delta, theta, alpha, and beta frequency bands. We characterized CogState One Card
Back Learning (OCL, memory) with diffusion model parameters drift rate, boundary
and non-decision time (NDT). Forward regression models showed that lower OCL
drift rate, slower accumulation of information needed for decision making was
linked to increased absolute and relative delta at occipital region. Lower drift
rate was also linked to decrease in OCL theta power at parietal region, with no
findings for ONB. Results show that cortical resting, eyes closed EEG rhythms are
related to memory in African American seniors endorsing cognitive concerns. This
study further supports the use of EEG as an easily accessible, cost-effective,
culture-fair, and noninvasive clinical measurement that could provide potentially
reliable diagnostic (and perhaps prognostic) information to differentiate at-risk
from stable African American seniors.
PMID- 27613570
TI - Demographic modelling with whole-genome data reveals parallel origin of similar
Pundamilia cichlid species after hybridization.
AB - Modes and mechanisms of speciation are best studied in young species pairs. In
older taxa, it is increasingly difficult to distinguish what happened during
speciation from what happened after speciation. Lake Victoria cichlids in the
genus Pundamilia encompass a complex of young species and polymorphic
populations. One Pundamilia species pair, P. pundamilia and P. nyererei, is
particularly well suited to study speciation because sympatric population pairs
occur with different levels of phenotypic differentiation and reproductive
isolation at different rocky islands within the lake. Genetic distances between
allopatric island populations of the same nominal species often exceed those
between the sympatric species. It thus remained unresolved whether speciation
into P. nyererei and P. pundamilia occurred once, followed by geographical range
expansion and interspecific gene flow in local sympatry, or if the species pair
arose repeatedly by parallel speciation. Here, we use genomic data and
demographic modelling to test these alternative evolutionary scenarios. We
demonstrate that gene flow plays a strong role in shaping the observed patterns
of genetic similarity, including both gene flow between sympatric species and
gene flow between allopatric populations, as well as recent and early gene flow.
The best supported model for the origin of P. pundamilia and P. nyererei
population pairs at two different islands is one where speciation happened twice,
whereby the second speciation event follows shortly after introgression from an
allopatric P. nyererei population that arose earlier. Our findings support the
hypothesis that very similar species may arise repeatedly, potentially
facilitated by introgressed genetic variation.
PMID- 27613571
TI - Documenting moral agency: a qualitative analysis of abortion decision making for
fetal indications.
AB - OBJECTIVES: We explored whether the decision-making process of women aborting a
pregnancy for a fetal indication fit common medical ethical frameworks. STUDY
DESIGN: We applied three ethical frameworks (principlism, care ethics, and
narrative ethics) in a secondary analysis of 30 qualitative interviews from women
choosing 2nd trimester abortion for fetal indications. RESULTS: All 30 women
offered reasoning consistent with one or more ethical frameworks. Principlism
themes included avoidance of personal suffering (autonomy), and sparing a child a
poor quality of life and painful medical interventions (beneficence/non
maleficence). Care ethics reasoning included relational considerations of family
needs and resources, and narrative ethics reasoning contextualized this
experience into the patient's life story. CONCLUSIONS: This population's
universal application of commonly accepted medical ethical frameworks supports
the position that patients choosing fetal indication abortions should be treated
as moral decision-makers and given the same respect as patients making decisions
about other medical procedures. IMPLICATIONS: These findings suggest recent
political efforts blocking abortion access should be reframed as attempts to
undermine the moral decision-making of women.
PMID- 27613572
TI - Indentation with atomic force microscope, Saccharomyces cerevisiae cell gains
elasticity under ethanol stress.
AB - During bioethanol fermentation process, Saccharomyces cerevisiae cell membrane is
the first target to be attacked by the accumulated ethanol. In such a prominent
position, S. cerevisiae cell membrane could reversely provide protection through
changing fluidity or elasticity secondary to remodeled membrane components or
structure during the fermentation process. However, there is yet to be a direct
observation of the real effect of the membrane compositional change. In this
study, atomic force microscope-based strategy was performed to determine Young's
modulus of S. cerevisiae to directly clarify ethanol stress-associated changes
and roles of S. cerevisiae cell membrane fluidity and elasticity. Cell survival
rate decreased while the cell swelling rate and membrane permeability increased
as ethanol concentration increased from 0% to 20% v/v. Young's modulus decreased
continuously from 3.76MPa to 1.53MPa while ethanol stress increased from 0% to
20% v/v, indicating that ethanol stress induced the S. cerevisiae membrane
fluidity and elasticity changes. Combined with the fact that membrane composition
varies under ethanol stress, to some extent, this could be considered as a forced
defensive act to the ethanol stress by S. cerevisiae cells. On the other hand,
the ethanol stress induced loosening of cell membrane also caused S. cerevisiae
cell to proactively remodel membrane to make cell membrane more agreeable to the
increase of environmental threat. Increased ethanol stress made S. cerevisiae
cell membrane more fluidized and elastic, and eventually further facilitated
yeast cell's survival.
PMID- 27613573
TI - Mechanisms of communication between mitochondria and lysosomes.
AB - Mitochondria and lysosomes have long been studied in the context of their classic
functions: energy factory and recycle bin, respectively. In the last twenty
years, it became evident that these organelles are much more than simple
industrial units, and are indeed in charge of many of cellular processes. Both
mitochondria and lysosomes are now recognized as far-reaching signaling
platforms, regulating many key aspects of cell and tissue physiology. It has
furthermore become clear that mitochondria and lysosomes impact each other. The
mechanisms underlying the cross-talk between these organelles are only now
starting to be addressed. In this review, we briefly summarize how mitochondria,
lysosomes and the lysosome-related process of autophagy affect each other in
physiology and pathology.
PMID- 27613574
TI - Anti-angiogenic effect of a Palladium(II)-Saccharinate Complex of Terpyridine in
vitro and in vivo.
AB - Anti-angiogenic activity of palladium (Pd)(II)-based complexes is unknown despite
their quite powerful anticancer activity. This study was therefore carried out to
evaluate both in vivo anti-angiogenic effect and in vitro cytotoxic activity of a
Pd(II)-based complex. ([Pd(sac)(terpy)](sac).4H2O(sac=saccharinate and
terpy=2,2':6',2"-terpyridine)) on HUVEC cells. The anti-angiogenic activity of
the complex was evaluated in vivo using the chick embryo chorioallantoic membrane
(CAM) assay, tube formation assay and the cytotoxicity was screened using the MTT
viability assays. The CAM treated with the complex (50MUg/pellet) showed a
strikingly high anti-angiogenic effect (score 1.1+/-0.2) compared to the positive
controls cortisone, prednisone and (+/-)-thalidomide (e.g. (+/-)-thalidomide
score 0.9+/-0.2) tested at the same concentration. Furthermore, the complex
showed neither membrane toxicity nor irritation at the tested concentration.
According to the MTT assays, the human umbilical vein endothelial cell (HUVEC)
viability was inhibited in a dose-dependent manner at tested concentrations (1.56
100MUM). Pd(II) complex also reduced the tube network at the lower dose than the
compared with thalidomide. These results suggest that the Pd(II)-complex has
strong anti-angiogenic activity, which adds an important feature to the
previously-described anticancer activity of the complex.
PMID- 27613575
TI - Comparison of stem cell behaviors between indigenous high and low-CD24 percentage
expressing cells of stem cells from apical papilla (SCAPs).
AB - CD24 was suggested as a marker to SCAPs and has been reported for a decade. CD24
has been shown to involve stem cell activities such as self-renewal,
proliferation and differentiation. However, the percentage variations of CD24
positive cells were reported among the studies. It is possible that this
variation may affect these SCAPs behaviors. In this study, the variation was
confirmed. To elucidate the influence of CD24 positive cells quantity on SCAPs
stem cell behaviors, the 3 cell lines with the most maximum and the least numbers
of CD24 positive cells (High-CD24 and Low-CD24 group) were selected to study.
Both groups expressed the same mesenchymal stem cell markers and negative to
hematopoietic marker. High-CD24 group demonstrated less self-renewal capacity by
lower colony-forming-unit count and pluripotency marker gene expressions.
However, cell proliferation was not different. In contrast, osteogenic and
adipogenic differentiation were better than Low-CD24 group. The early stage of
root development demonstrated higher CD24 expressing cells than later stage. In
conclusion, quantity of CD24 expressing cells influenced SCAPs self-renewal and
multi-lineage differentiation but did not influence on cell proliferation. Stage
of root development influenced to CD24 expressing cell numbers.
PMID- 27613576
TI - Available technologies and clinical applications of targeted chemotherapy in
pancreatic cancer.
AB - The incidence of pancreatic cancer, the fourth leading cause of cancer death in
United States, is increasing worldwide. Even though the cure rate has doubled in
40 years, it is abysmally poor at 6-7%. As surgical resection remains the only
curative treatment and less than 20% of the newly diagnosed cancers are
resectable, the major burden of disease management lies in early diagnosis, good
prognostication, and proper neo-adjuvant and/or adjuvant therapy. With advancing
technologies and their ease of availability, researchers have better tools to
understand pancreatic cancer. In the post-genetic era, proteomic,
phosphoproteomic, metabolomic, and more have brought us to a multi-omics era.
These newer avenues bring promises of better screening modalities, less invasive
diagnostics and monitoring, subtyping of pancreatic cancer, and fine tuning the
treatment modalities not only to the right stage of tumor but also to the right
tumor biology. As the multitudes of technologies are generating extensive amounts
of incongruous data, they are giving clinicians a lot of non-actionable
information. In this paper, we wish to encompass the newer technologies, sub
classifications, and future treatment modalities in personalized care of patients
with pancreatic cancer.
PMID- 27613577
TI - Molecular targeted therapy for pancreatic adenocarcinoma: A review of completed
and ongoing late phase clinical trials.
AB - Molecular targeted therapy is widely utilized and effective in a number of solid
tumors. In pancreatic adenocarcinoma, targeted therapy has been extensively
evaluated; however, survival improvement of this aggressive disease using a
targeted strategy has been minimal. The purpose of this study is to review
therapeutic molecular targets in completed and ongoing later phase (II and III)
clinical trials to have a better understanding of the rationale and progress
towards targeted molecular therapies for pancreatic cancer. The PubMed database
and the NCDI clinical trial website (www.clinicaltrials.gov) were queried to
identify phase II and III completed and published (PubMed) and ongoing
(clinicaltrials.gov) trials using the keywords: pancreatic cancer and molecular
targeted therapy. The search engines were further limited by adding Phase II or
III, active enrollment and North American. A total of 14 completed and published
phase II/III clinical trials and 17 ongoing trials were identified. Evaluated
strategies included inhibition of growth factor receptors (EGFR, PDGFR, VGFR, IGF
1R), tyrosine kinase inhibitors, MEK1/2, mTOR blockade and PI3K and HER2-neu
pathway inhibitors. Only one trial conducted by the National Cancer Institute of
Canada and the PANTAR trial have demonstrated a survival improvement from EGFR
inhibition using erlotinib. These trials ultimately led to FDA approval of
erlotinib/Tarceva in advanced stage disease. It remains unclear whether new
combinations of cytotoxic chemotherapy or immunotherapy plus molecular targeted
therapy will be beneficial in management of pancreatic adenocarcinoma. Despite a
number of phase II and III trials, to date, only erlotinib has emerged as an
approved targeted therapy in pancreatic adenocarcinoma. There are several ongoing
late phase trials evaluating a number of targets, the results of which will
become available over the next 1 to 2 years.
PMID- 27613578
TI - Sonographic evaluation of patellar clunk syndrome following total knee
arthroplasty.
AB - Patellar clunk syndrome is a painful mechanical phenomenon that may develop
following total knee arthroplasty. The diagnosis is usually made clinically, but
cross-sectional imaging may be needed to confirm the clinical suspicion.
Sonographic confirmation of patellar clunk syndrome can be obtained by directly
visualizing the soft tissue proliferation deep to the distal quadriceps tendon
and by dynamically demonstrating the clunking tissue during flexion and extension
of the knee. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:105-107, 2017.
PMID- 27613579
TI - Codon optimality controls differential mRNA translation during amino acid
starvation.
AB - It is common wisdom that codon usage bias has evolved in the selection for
efficient translation, in which highly expressed genes are encoded predominantly
by optimal codons. However, a growing body of evidence suggests regulatory roles
for non-optimal codons in translation dynamics. Here we report that in mammalian
cells, non-optimal codons play a critical role in promoting selective mRNA
translation during amino acid starvation. During starvation, in contrast to genes
encoding ribosomal proteins whose translation is highly sensitive to amino acid
deprivation, translation of genes involved in the cellular protein degradation
pathways remains unaffected. We found that these two gene groups bear different
codon composition, with non-optimal codons being highly enriched in genes
encoding the ubiquitin-proteasome system. Supporting the selective tRNA charging
model originally proposed in Escherichia coli, we demonstrated that tRNA
isoacceptors decoding rare codons are maintained in translating ribosomes under
amino acid starvation. Finally, using luciferase reporters fused with endogenous
gene-derived sequences, we show that codon optimality contributes to differential
mRNA translation in response to amino acid starvation. These results highlight
the physiological significance of codon usage bias in cellular adaptation to
stress.
PMID- 27613580
TI - tRNA base methylation identification and quantification via high-throughput
sequencing.
AB - Eukaryotic transfer RNAs contain on average 14 modifications. Investigations of
their biological functions require the determination of the modification sites
and the dynamic variations of the modification fraction. Base methylation
represents a major class of tRNA modification. Although many approaches have been
used to identify tRNA base methylations, including sequencing, they are generally
qualitative and do not report the information on the modification fraction.
Dynamic mRNA modifications have been shown to play important biological roles;
yet, the extent of tRNA modification fractions has not been reported
systemically. Here we take advantage of a recently developed high-throughput
sequencing method (DM-tRNA-seq) to identify and quantify tRNA base methylations
located at the Watson-Crick face in HEK293T cells at single base resolution. We
apply information derived from both base mutations and positional stops from
sequencing using a combination of demethylase treatment and cDNA synthesis by a
thermophilic reverse transcriptase to compile a quantitative "Modification Index"
(MI) for six base methylations in human tRNA and rRNA. MI combines the metrics
for mutational and stop components from alignment of sequencing data without
demethylase treatment, and the modifications are validated in the sequencing data
upon demethylase treatment. We identify many new methylation sites in both human
nuclear and mitochondrial-encoded tRNAs not present in the RNA modification
databases. The potentially quantitative nature of the MI values obtained from
sequencing is validated by primer extension of several tRNAs. Our approach should
be widely applicable to identify tRNA methylation sites, analyze comparative
fractional modifications, and evaluate the modification dynamics between
different samples.
PMID- 27613581
TI - Heterogeneous structures formed by conserved RNA sequences within the HIV reverse
transcription initiation site.
AB - Reverse transcription is a key process in the early steps of HIV infection. This
process initiates within a specific complex formed by the 5' UTR of the HIV
genomic RNA (vRNA) and a host primer tRNALys3 Using nuclear magnetic resonance
(NMR) spectroscopy and single-molecule fluorescence spectroscopy, we detect two
distinct conformers adopted by the tRNA/vRNA initiation complex. We directly show
that an interaction between the conserved 8-nucleotide viral RNA primer
activation signal (PAS) and the primer tRNA occurs in one of these conformers.
This intermolecular PAS interaction likely induces strain on a vRNA
intramolecular helix, which must be broken for reverse transcription to initiate.
We propose a mechanism by which this vRNA/tRNA conformer relieves the kinetic
block formed by the vRNA intramolecular helix to initiate reverse transcription.
PMID- 27613582
TI - Abnormal glucose regulation increases stroke risk in minor ischemic stroke or
TIA.
AB - OBJECTIVE: To investigate whether abnormal glucose regulation contributes to a
new stroke in patients with a minor ischemic stroke or TIA. METHODS: We derived
data from the Clopidogrel in High-risk patients with Acute Nondisabling
Cerebrovascular Events trial. Patients with a minor stroke or TIA were
categorized into 3 groups: patients with diabetes mellitus (DM), impaired fasting
glucose (IFG), and normal fasting plasma glucose. The primary outcome was a new
stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between
glucose regulation status and risk of stroke by multivariable Cox regression
models adjusted for potential covariates. RESULTS: Among 5,135 included patients,
1,587 (30.9%), 409 (8.0%), and 3,139 (61.1%) patients were identified as DM, IFG,
and normal glucose, respectively. Compared with normal glucose, IFG (11.0% vs
6.9%; adjusted hazard ratio [adj HR] 1.57, 95% confidence interval [CI] 1.13
2.19) and DM (15.8% vs 6.9%; adj HR 2.38, 95% CI 1.97-2.88) were associated with
increased risk of stroke at 3 months after a minor stroke or TIA after adjusted
for potential covariates. We found a weak J-shaped association between fasting
plasma glucose and risk of stroke with a nadir of 4.9 mmol/L. CONCLUSIONS: Both
IFG and DM were associated with an increased risk of stroke in patients with a
minor stroke or TIA. CLINICALTRIALSGOV IDENTIFIER: NCT00979589.
PMID- 27613583
TI - Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral
amyloid angiopathy.
AB - OBJECTIVES: To identify in vivo MRI markers that might correlate with cerebral
microinfarcts (CMIs) on autopsy in patients with cerebral amyloid angiopathy
(CAA). METHODS: We included patients with neuropathologic evidence of CAA on
autopsy and available antemortem brain MRI. Clinical characteristics and in vivo
MRI markers of CAA-related small vessel disease were recorded, including white
matter hyperintensities, cerebral microbleeds, cortical superficial siderosis,
and centrum semiovale perivascular spaces. In addition, the presence of
intracerebral hemorrhage on MRI was assessed. Evaluation of the presence and
number of CMIs was performed in 9 standard histology sections. RESULTS: Of 49
analyzed patients with CAA, CMIs were present in 36.7%. The presence of >=1 CMIs
on autopsy was associated with higher numbers of microbleeds on antemortem MRI
(median 8 [interquartile range 2.5-33.0] vs 1 [interquartile range 0-3], p =
0.003) and with the presence of intracerebral hemorrhage (44.4% vs 16.1%, p =
0.03). No associations between CMIs and other in vivo MRI markers of CAA were
found. In a multivariable model adjusted for severe CAA pathology, higher numbers
of microbleeds were independent predictors of the presence of CMIs on pathology.
CONCLUSIONS: CMIs are a common finding at autopsy in patients with CAA. The
strong association between MRI-observed microbleeds and CMIs at autopsy may
suggest a shared underlying pathophysiologic mechanism between these lesions.
PMID- 27613584
TI - Special issue, 'Central and peripheral nerve influence on cardiac function in
health and disease'.
PMID- 27613586
TI - Effects of Cervical Extension on Deformation of Intervertebral Disk and Migration
of Nucleus Pulposus.
AB - BACKGROUND: We theorized that active cervical extension should influence the
position of the nucleus pulposus (NP) within the intervertebral disk (IVD) in the
sagittal plane. Although several studies on the lumbar IVD have been conducted,
there are no quantitative data for in vivo positional changes of the NP in the
cervical IVD. OBJECTIVE: To evaluate the influence and mechanism of cervical
extension on the deformation and migration of IVD and NP in the sagittal plane
and understand underlying mechanisms of the extension maneuver. DESIGN:
Asymptomatic subjects underwent magnetic resonance imaging while supine with
their cervical spines in neutral and extended positions. SETTING: Academic
medical center. PARTICIPANTS: Ten young, healthy male participants (age range 19
30 years; mean 22.4 +/- 1.64 years). METHODS: T2-weighted sagittal images from C3
C4 to C6-C7 of subjects in both neutral and extension positions were analyzed.
MAIN OUTCOME MEASUREMENTS: Deformation of IVD and positional change of NP were
quantified and compared between neutral and extension positions. Intersegmental
angles between vertebrae, horizontal positions of anterior and posterior IVD and
NP margins, IVD outer and inner heights, and sagittal morphology of NP were
quantified and compared between the neutral and extension positions. Correlations
between the measured parameters and segmental extension angle were also
investigated. RESULTS: Anterior and posterior IVD margins moved posteriorly with
respect to the vertebral body in extension. Both NP margins remained unchanged
relative to the vertebral body but moved anteriorly with respect to the IVD. IVD
outer and inner heights in the anterior region increased in extension, and
morphological changes of the NP were less noticeable when compared with its
relative migration within the IVD. Most of the intradiskal changes were linearly
correlated with the segmental extension angle. CONCLUSIONS: Cervical extension
induces anterior migration of the NP away from the posterior disk margin and may
have a clinical effect on diskogenic neck pain resulting from internal disk
disruption. LEVEL OF EVIDENCE: Not applicable.
PMID- 27613587
TI - Differences in orthotic design for thumb osteoarthritis and its impact on
functional outcomes: A scoping review.
AB - BACKGROUND: Orthoses are a well-known intervention for the treatment of thumb
osteoarthritis; however, there is a multitude of orthotic designs and not enough
evidence to support the efficacy of specific models. OBJECTIVE: To examine the
influence of different orthoses on pain, hand strength, and hand function of
patients with thumb osteoarthritis. STUDY DESIGN: Literature review. METHODS: A
scoping literature review of 14 publications reporting orthotic interventions for
patients with thumb osteoarthritis was conducted. Functional outcomes and
measures were extracted and analyzed. RESULTS: In total, 12 studies reported
improvements in pain and hand strength after the use of thumb orthoses.
Comparisons between different orthotic designs were inconclusive. CONCLUSION: The
use of orthoses can decrease pain and improve hand function of patients with
thumb osteoarthritis; however, the effectiveness of different orthoses still
needs support through adequate evidence. Clinical relevance Multiple orthoses for
thumb osteoarthritis are available. Although current studies support their use to
improve pain and hand function, there is no evidence to support the efficacy of
specific orthotic designs. Improved functional outcomes can be achieved through
the use of short orthoses, providing thumb stabilization without immobilizing
adjacent joints.
PMID- 27613585
TI - Parasitism by larval tapeworms genus Spirometra in South American amphibians and
reptiles: new records from Brazil and Uruguay, and a review of current knowledge
in the region.
AB - Spargana are plerocercoid larvae of cestode tapeworms of the genus Spirometra,
Family Diphyllobothriidae, parasitic to frogs, reptiles, birds and mammals. This
parasitic disease in humans can be transmitted through the use and consumption of
amphibians and reptiles. The available knowledge about Spirometra in South
America is scarce, and there are only a few reports on the occurrence of
sparganum in amphibians and reptiles, many of them published in old papers not
easily available to researchers. In this work we present a review on this topic,
provide new records in two species of amphibians and 7 species of reptiles from
Brazil and Uruguay respectively. We also summarize current knowledge of
Spirometra in the continent, along with an updated of host taxonomy. We could
gather from the literature a total of 15 studies about amphibian and reptile
hosts, published between 1850 and 2016, corresponding to 43 case reports, mostly
from Brazil (29) and Uruguay (8), Argentina (3), Peru (2), and Venezuela (1); the
majority of them related to reptiles (five lizards and 26 snake species), and 14
corresponded to amphibians (9 anurans). Plerocercoid larvae were located in
different organs of the hosts, such as subcutaneous tissue, coelomic cavity,
peritoneum, and musculature. The importance of amphibians and reptiles in the
transmission of the disease to humans in South America is discussed. Relevant
issues to be studied in the near future are the taxonomic characterization of
Spirometra in the region and the biological risk of reptile meat for aboriginal
and other rural communities.
PMID- 27613588
TI - A smartphone photogrammetry method for digitizing prosthetic socket interiors.
AB - BACKGROUND AND AIM: Prosthetic CAD/CAM systems require accurate 3D limb models;
however, difficulties arise when working from the person's socket since current
3D scanners have difficulties scanning socket interiors. While dedicated scanners
exist, they are expensive and the cost may be prohibitive for a limited number of
scans per year. A low-cost and accessible photogrammetry method for socket
interior digitization is proposed, using a smartphone camera and cloud-based
photogrammetry services. TECHNIQUE: 15 two-dimensional images of the socket's
interior are captured using a smartphone camera. A 3D model is generated using
cloud-based software. Linear measurements were comparing between sockets and the
related 3D models. DISCUSSION: 3D reconstruction accuracy averaged 2.6 +/- 2.0 mm
and 0.086 +/- 0.078 L, which was less accurate than models obtained by high
quality 3D scanners. However, this method would provide a viable 3D digital
socket reproduction that is accessible and low-cost, after processing in
prosthetic CAD software. Clinical relevance The described method provides a low
cost and accessible means to digitize a socket interior for use in prosthetic
CAD/CAM systems, employing a smartphone camera and cloud-based photogrammetry
software.
PMID- 27613589
TI - Elastomeric liners for people with transtibial amputation: Survey of
prosthetists' clinical practices.
AB - BACKGROUND: A diverse range of elastomeric liner products are available to people
with transtibial amputation. However, little information is available about how
prosthetists select the product best suited to each patient. OBJECTIVES: To
determine how prosthetists obtain information about liners, which features are
most relevant to the selection process, and which products are used most for
patients with transtibial amputation. STUDY DESIGN: Cross-sectional survey.
METHODS: A custom online survey was developed to solicit information about
prosthetists' liner selection practices. Prosthetists with experience managing
transtibial patients were recruited via advertisements posted in magazines, at
conferences, and on a listserv. Responses were analyzed to characterize
prosthetists' liner selection practices. RESULTS: Data from 106 experienced
prosthetists (mean age: 44.4 years, mean experience: 15.7 years) were included.
Most prosthetists (94%) obtained liner information from manufacturer
representatives, websites, or literature. On average, respondents factored nine
different liner characteristics into their selection processes. Prosthetists
reported experience with 16 unique liner products with their transtibial
patients, but routinely used fewer than 3. CONCLUSION: Although many different
prosthetic liners are available, prosthetists regularly use only a few select
liner products. Tools or strategies to objectively compare prosthetic liners
across manufacturers are likely needed to facilitate more diverse prescription
practices. Clinical relevance Knowledge of prosthetists' prosthetic liner
selection practices may guide development of evidence-based resources or tools to
facilitate matching patients with appropriate liners. Results of this study may
also inform researchers and manufacturers about desirable liner characteristics
and direct development of novel liner products to address prosthetists' clinical
needs.
PMID- 27613590
TI - Gastrocnemius operating length with ankle foot orthoses in cerebral palsy.
AB - BACKGROUND: Many individuals with cerebral palsy wear ankle foot orthoses during
daily life. Orthoses influence joint motion, but how they impact muscle remains
unclear. In particular, the gastrocnemius is commonly stiff in cerebral palsy.
Understanding whether orthoses stretch or shorten this muscle during daily life
may inform orthosis design and rehabilitation. OBJECTIVES: This study
investigated the impact of different ankle foot orthoses on gastrocnemius
operating length during walking in children with cerebral palsy. STUDY DESIGN:
Case series, within subject comparison of gastrocnemius operating length while
walking barefoot and with two types of ankle foot orthoses. METHODS: We performed
gait analyses for 11 children with cerebral palsy. Each child was fit with two
types of orthoses: a dynamic ankle foot orthosis (Cascade dynamic ankle foot
orthosis) and an adjustable dynamic response ankle foot orthosis (Ultraflex ankle
foot orthosis). Musculoskeletal modeling was used to quantify gastrocnemius
musculotendon operating length and velocity with each orthosis. RESULTS: Walking
with ankle foot orthoses could stretch the gastrocnemius more than barefoot
walking for some individuals; however, there was significant variability between
participants and orthoses. At least one type of orthosis stretched the
gastrocnemius during walking for 4/6 and 3/5 of the Gross Motor Functional
Classification System Level I and III participants, respectively. AFOs also
reduced peak gastrocnemius lengthening velocity compared to barefoot walking for
some participants, with greater reductions among the Gross Motor Functional
Classification System Level III participants. Changes in gastrocnemius operating
length and lengthening velocity were related to changes in ankle and knee
kinematics during gait. CONCLUSION: Ankle foot orthoses impact gastrocnemius
operating length during walking and, with proper design, may assist with
stretching tight muscles in daily life. Clinical relevance Determining whether
ankle foot orthoses stretch tight muscles can inform future orthotic design and
potentially provide a platform for integrating therapy into daily life. However,
stretching tight muscles must be balanced with other goals of orthoses such as
improving gait and preventing bone deformities.
PMID- 27613591
TI - Pressure-induced localised granuloma annulare following use of an elbow splint.
AB - BACKGROUND: Granuloma annulare is a benign, inflammatory skin disorder with no
distinct aetiology or widely accepted pathogenic process. Case description and
Methods: We report a case of a 71-year old female with a 4-year history of an
erythematous annulopapular lesion to the lateral aspect of her right forearm from
a pressure pleat ridge in a high-density polyethylene plastic elbow orthosis to
immobilise a prior radial head fracture. Morphological and histopathological
assessment was consistent for granuloma annulare. Findings and Outcomes: The
granuloma annulare was ameliorated after 3 months of high-potency topical
steroids under occlusive dressing. CONCLUSION: This case highlights an atypical
presentation of a pressure-induced patch of localised granuloma annulare
persisting long-term after temporary use of a high-density polyethylene orthosis
with a pleated point ridge. Special care should be taken when choosing the
appropriate orthosis in patients with sensitive skin conditions. Moulded orthoses
can have defects after manufacturing that can lead to localised skin irritation,
inflammation and subsequent rash formation. Clinical relevance Appropriate
casting and splint moulding should be taken into special consideration in
patients with sensitive skin conditions. This prevents or diminishes the chance
inducing or exacerbating skin conditions.
PMID- 27613592
TI - Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An.
gambiae.
AB - Pyrethroid resistance is widespread in the malaria vector Anopheles gambiae
leading to concerns about the future efficacy of bednets with pyrethroids as the
sole active ingredient. The incorporation of pyriproxyfen (PPF), a juvenile
hormone analogue, into pyrethroid treated bednets is being trialed in Africa.
Pyrethroid resistance is commonly associated with elevated levels of P450
expression including CYPs 6M2, 6P2, 6P3, 6P4, 6P5, 6Z2 and 9J5. Having expressed
these P450s in E. coli we find all are capable of metabolizing PPF. Inhibition of
these P450s by permethrin, deltamethrin and PPF was also examined. Deltamethrin
and permethrin were moderate inhibitors (IC50 1-10 MUM) of diethoxyfluorescein
(DEF) activity for all P450s apart from CYP6Z2 (IC50 > 10 MUM), while PPF
displayed weaker inhibition of all P450s (IC50 > 10 MUM) except CYP's 6Z2 and 6P2
(IC50 1-10 MUM). We found evidence of low levels of cross resistance between PPF
and other insecticide classes by comparing the efficacy of PPF in inhibiting
metamorphosis and inducing female sterility in an insecticide susceptible strain
of An. gambiae and a multiple resistant strain from Cote d'Ivoire.
PMID- 27613594
TI - NHS announces online symptom checker.
PMID- 27613593
TI - The relation between health insurance and management of hypertension in Shanghai,
China: a cross-sectional study.
AB - BACKGROUND: We aimed to investigate the management of hypertension in Shanghai,
China and to examine whether there was any difference of hypertension management
among people enrolled in different health insurances. METHODS: In this cross
sectional study, a total of 31,531 residents were selected in Shanghai, using a
randomized, stratified, multi-stage sampling method, and were asked to provide
their status of hypertension, condition of hypertension management, health
insurances and other demographic information. A weighted propensity score model
was used to adjust confounders and to analyze the differences on hypertension
management among hypertension patients enrolled in different health insurances.
RESULTS: In Shanghai, most hypertension patients achieved good management of
hypertension. However, patients enrolled in the New Cooperative Medical Scheme or
the Urban Resident Basic Medical Insurance scheme were more likely to achieve
publicity of precautionary knowledge about hypertension (OR = 2.36 [95 % CI
:1.96,2.85] and 1.28 [95 % CI:1.12,1.45], respectively) and had their blood
pressure under control (OR = 1.33 [95 % CI :1.09,1.62] and 1.22 [95 %
CI:1.05,1.42], respectively) than patients enrolled in the Urban Employee Basic
Health Insurance scheme. CONCLUSION: The study provided a comprehensive
description of hypertension in Shanghai, China. To support the management of
hypertension, publicity of hypertension prevention knowledge should be improved,
especially to people enrolled in the Urban Employee Basic Health Insurance
scheme.
PMID- 27613596
TI - Association between the vascular endothelial growth factor single nucleotide
polymorphisms and diabetic retinopathy risk: A meta-analysis.
AB - BACKGROUND: The aim of the present study was to reveal the relationship between
vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs)
and susceptibility to diabetic retinopathy (DR). METHODS: A literature review was
conducted (PubMed, Web of Science, Embase) to identify papers about VEGF SNPs and
DR published up to 23 September 2015. The VEGF gene SNPs analyzed with regard to
DR susceptibility were rs2010963 (G > C), rs833061 (T > C), rs699947 (C > A),
rs3025039 (C > T) and rs1570360 (G > A). Pooled odds ratios (OR) and 95%
confidence intervals (CI) were calculated, and meta-analyses were performed using
fixed or random effects models. RESULTS: Sixteen studies were included in the
meta-analysis. Significant associations between the rs3025039 (C > T)
polymorphism and increased DR risk were found in the allele model (T/C; pooled OR
1.60, 95% CI 1.07-2.41, P = 0.02), homozygote model (TT/CC; pooled OR 2.08, 95%
CI 1.29-3.35, P = 0.003), heterozygote model (TC/CC; pooled OR 1.68, 95% CI 1.04
2.72, P = 0.04), dominant model (TT+TC/CC; pooled OR 1.72, 95% CI 1.06-2.80, P =
0.03), and recessive model (TT/TC+CC; pooled OR 1.80, 95% CI 1.12-2.90, P =
0.02). For rs833061, a significant association between VEGF SNPs and DR was found
only in the allele model (C/T; pooled OR 6.34, 95% CI 2.10-19.14, P = 0.001).
CONCLUSIONS: The rs3025039 and rs833061 SNPs are most likely associated with an
increased risk of DR. The T allele in rs3025039 and the C allele in rs833061 are
associated with increased DR susceptibility.
PMID- 27613595
TI - Comparison of the types of candidate reference samples for quality control of
human epidermal growth factor receptor 2 status detection.
AB - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is as a target gene
for trastuzumab in patients with breast cancer. Accurate determination of HER2
status and strict quality control are necessary to ensure reproducibility and
accuracy of the techniques used for the determination of HER2 status. METHODS: We
used three different types of samples: formalin-fixed and paraffin-embedded
(FFPE) samples prepared from cell lines, agarose gel samples using cell lines,
and xenograft tumor samples. One cell line for FFPE or xenografts did not
overexpress HER2, while the others showed different levels of HER2
overexpression. We compared the morphology, HER2 gene amplification status, and
HER2 protein expression status of these samples with those of clinical specimens.
RESULTS: We successfully produced three kinds of samples for quality control.
Cells from the cell line-sample sections were dispersed while those from the
agarose gel-sample sections and xenograft tumor sample sections (prepared from
the both cell lines) were concentrated in one area. The FISH results for all
three kinds of samples were as expected. The IHC results of the cell line samples
and xenograft tumor samples were as expected, but the staining level of the
agarose gel samples, using HER2-overexpressed cell lines was weak which might be
regarded as a false negative result. CONCLUSIONS: Xenograft tumor samples might
be used as an additional option for quality control in FISH and IHC. However, it
might not replace the clinical specimen quality controls directly.
PMID- 27613597
TI - End of life hospitalisations differ for older Australian women according to death
trajectory: a longitudinal data linkage study.
AB - BACKGROUND: Hospitalisations are the prime contributor to healthcare expenditure,
with older adults often identified as high hospital users. Despite the apparent
high use of hospitals at the end of life, limited evidence currently exists
regarding reasons for hospitalisation. Understanding complex end of life care
needs is required for future health care planning as the global population ages.
This study aimed to investigate patterns of hospitalisation in the last year of
life by cause of death (COD) as well as reasons for admission and short-term
predictors of hospital use. METHODS: Survey data from 1,205 decedents from the
1921-1926 cohort of the Australian Longitudinal Study on Women's Health were
matched with the state-based hospital records and the National Death Index.
Hospital patterns based on COD were graphically summarised and multivariate
logistic regression models examined the impact of short-term predictors of length
of stay (LOS). RESULTS: 85 % of women had at least one admission in the last year
of life; and 8 % had their first observed admission during this time. Reasons for
hospitalisation, timing of admissions and LOS differed by COD. Women who died of
cancer, diabetes and 'other' causes were admitted earlier than women who died of
organ failure, dementia and influenza. Women who died of organ failure overall
spent the longest time in hospital, and women with cancer had the highest median
LOS. Longer LOS was associated with previous short- and medium-term-
hospitalisations and type of hospital separation. CONCLUSIONS: Reducing acute
care admissions and LOS at the end of life is complex and requires a shift in
perceptions and treatment regarding end of life care and chronic disease
management.
PMID- 27613599
TI - Embryonic expression patterns of Hox genes in the oligochaete annelid Tubifex
tubifex.
AB - We have cloned and characterized the expression of seven Hox genes (designated
Ttu-lab, Ttu-Dfd, Ttu-Scr1, Ttu-Scr2, Ttu-Lox5, Ttu-Lox4 and Ttu-Lox2) from the
oligochaete annelid Tubifex tubifex. RT-PCR analyses show that except for Ttu
Lox4 and Ttu-Lox2 which begin expression as early as cleavage stages, Tubifex Hox
genes are expressed during stages 13-18 when embryos undergo germ band formation,
segmentation and body elongation. In terms of combination of tissues (or organs)
exhibiting positive cells, the Tubifex Hox genes examined in this study are
classified into three groups. Ttu-lab, Ttu-Scr1 and Ttu-Lox5 are expressed only
in the ventral nerve cord; Ttu-Scr2 and Ttu-Lox4 are expressed not only in the
ventral nerve cord but also in distinct lateral segmental tissues; and Ttu-Dfd
and Ttu-Lox2 are expressed not only in the segmental ectoderm along the length of
the AP body axis but also in the prostomium. Anterior expression boundaries of
Ttu-lab, Ttu-Scr1, Ttu-Lox5 and Ttu-Lox4 are at segments 3, 4, 5, and 9,
respectively. Anterior expression boundary of Ttu-Scr2 is at segment 2, and Ttu
Dfd and Ttu-Lox2 are expressed even at the anteriormost portion, the prostomium.
These observations suggest that as in other annelids, so-called "spatial
colinearity" of anterior expression boundaries of Hox genes has been conserved in
the oligochaetes. It is also evident that there are some oligochaete Hox genes
which violate the spatial colinearity rule.
PMID- 27613598
TI - Two-photon polymerized "nichoid" substrates maintain function of pluripotent stem
cells when expanded under feeder-free conditions.
AB - BACKGROUND: The use of pluripotent cells in stem cell therapy has major
limitations, mainly related to the high costs and risks of exogenous conditioning
and the use of feeder layers during cell expansion passages. METHODS: We
developed an innovative three-dimensional culture substrate made of "nichoid"
microstructures, nanoengineered via two-photon laser polymerization. The nichoids
limit the dimension of the adhering embryoid bodies during expansion, by
counteracting cell migration between adjacent units of the substrate by its
microarchitecture. We expanded mouse embryonic stem cells on the nichoid for 2
weeks. We compared the expression of pluripotency and differentiation markers
induced in cells with that induced by flat substrates and by a culture layer made
of kidney-derived extracellular matrix. RESULTS: The nichoid was found to be the
only substrate, among those tested, that maintained the expression of the OCT4
pluripotency marker switched on and, simultaneously, the expression of the
differentiation markers GATA4 and alpha-SMA switched off. The nichoid promotes
pluripotency maintenance of embryonic stem cells during expansion, in the absence
of a feeder layer and exogenous conditioning factors, such as the leukocyte
inhibitory factor. CONCLUSIONS: We hypothesized that the nichoid microstructures
induce a genetic reprogramming of cells by controlling their cytoskeletal
tension. Further studies are necessary to understand the exact mechanism by which
the physical constraint provided by the nichoid architecture is responsible for
cell reprogramming. The nichoid may help elucidate mechanisms of pluripotency
maintenance, while potentially cutting the costs and risks of both feed
conditioning and exogenous conditioning for industrial-scale expansion of stem
cells.
PMID- 27613600
TI - Expression profiles of the Galpha subunits during Xenopus tropicalis embryonic
development.
AB - Heterotrimeric G protein signaling plays major roles during different cellular
events. However, there is a limited understanding of the molecular mechanisms
underlying G protein control during embryogenesis. G proteins are highly
conserved and can be grouped into four subfamilies according to sequence homology
and function. To further studies on G protein function during embryogenesis, the
present analysis identified four Galpha subunits representative of the different
subfamilies and determined their spatiotemporal expression patterns during
Xenopus tropicalis embryogenesis. Each of the Galpha subunit transcripts was
maternally and zygotically expressed, and, as development progressed, dynamic
expression patterns were observed. In the early developmental stages, the Galpha
subunits were expressed in the animal hemisphere and dorsal marginal zone. While
expression was observed at the somite boundaries, in vascular structures, in the
eye, and in the otic vesicle during the later stages, expression was mainly found
in neural tissues, such as the neural tube and, especially, in the cephalic
vesicles, neural crest region, and neural crest-derived structures. Together,
these results support the pleiotropism and complexity of G protein subfamily
functions in different cellular events. The present study constitutes the most
comprehensive description to date of the spatiotemporal expression patterns of
Galpha subunits during vertebrate development.
PMID- 27613602
TI - Mucilaginibacter antarcticus sp. nov., isolated from tundra soil.
AB - The novel, pale yellow bacterial strain, designated S14-88T, was isolated from a
tundra soil near Antarctic Peninsula, South Shetland Islands, and its taxonomic
position was investigated by a genotypic and phenotypic analysis. Cells were
facultatively anaerobic, Gram-stain-negative, non-motile and rod-shaped. Growth
occurred at 4-28 degrees C (optimum at 15 degrees C), at pH 7.0-8.0 (optimum at
7.0) and with 0-0.6 % (w/v) NaCl (optimum, no NaCl). Phylogenetic analysis based
on 16S rRNA gene sequences indicated that strain S14-88T formed a lineage within
the genus Mucilaginibacter. The 16S rRNA gene sequence similarity between strain
S14-88T and the type strains of related species ranged from 92.2 to 96.5 %, and
the 16S rRNA gene sequence of S14-88T showed highest similarity of 96.5 % to
Mucilaginibacter soyangensis HME6664T. The major cellular fatty acids of strain
S14-88T were iso-C15 : 0 and summed feature 3 (C16 : 1omega7c and/or C16 :
1omega6c). The major respiratory quinone was menaquinone MK-7, and the main polar
lipid was phosphatidylethanolamine. The DNA G+C content of strain S14-88T was
42.3 mol%. On the basis of the evidence presented in this study, strain S14-88T
is considered to represent a novel species of the genus Mucilaginibacter, for
which the name Mucilaginibacter antarcticus sp. nov. is proposed. The type strain
is S14-88T (=CCTCC AB 2015321T=KCTC 52232T).
PMID- 27613601
TI - Identification of oncogenic driver mutations by genome-wide CRISPR-Cas9 dropout
screening.
AB - BACKGROUND: Genome-wide CRISPR-Cas9 dropout screens can identify genes whose
knockout affects cell viability. Recent CRISPR screens detected thousands of
essential genes required for cellular survival and key cellular processes;
however discovering novel lineage-specific genetic dependencies from the many
hits still remains a challenge. RESULTS: To assess whether CRISPR-Cas9 dropout
screens can help identify cancer dependencies, we screened two human cancer cell
lines carrying known and distinct oncogenic mutations using a genome-wide sgRNA
library. We found that the gRNA targeting the driver mutation EGFR was one of the
highest-ranking candidates in the EGFR-mutant HCC-827 lung adenocarcinoma cell
line. Likewise, sgRNAs for NRAS and MAP2K1 (MEK1), a downstream kinase of mutant
NRAS, were identified among the top hits in the NRAS-mutant neuroblastoma cell
line CHP-212. Depletion of these genes targeted by the sgRNAs strongly correlated
with the sensitivity to specific kinase inhibitors of the EGFR or RAS pathway in
cell viability assays. In addition, we describe other dependencies such as TBK1
in HCC-827 cells and TRIB2 in CHP-212 cells which merit further investigation.
CONCLUSIONS: We show that genome-wide CRISPR dropout screens are suitable for the
identification of oncogenic drivers and other essential genes.
PMID- 27613603
TI - Corrigendum to "Mechanisms and kinetics of proliferation and fibrosis development
in a mouse model of thyrocyte hyperplasia" [Cell. Immunol. 304-305 (2016) 16-26].
PMID- 27613605
TI - "Pitted" lesions in dermatology.
AB - Cutaneous pitting, dimpling, or depressions are frequently dealt with in clinical
practice. Such lesions may be primary manifestations of a disorder or develop as
secondary changes during the course of the disease. Cutaneous pitting may be a
manifestation of certain genodermatoses and internal disorders when it serves as
a marker of such conditions. This article describes various types of pitted
lesions affecting the ectodermal structures (skin, nails, and teeth) and their
clinical significance along with brief description of the associated conditions.
PMID- 27613604
TI - Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically
distinct populations.
AB - BACKGROUND: The heterogeneity and tumourigenicity of metastatic melanoma is
attributed to a cancer stem cell model, with CD133 considered to be a cancer stem
cell marker in melanoma as well as other tumours, but its role has remained
controversial. METHODS: We iteratively sorted CD133+ and CD133- cells from 3
metastatic melanoma cell lines, and observed tumourigenicity and phenotypic
characteristics over 7 generations of serial xeno-transplantation in NOD/SCID
mice. RESULTS: We demonstrate that iterative sorting is required to make highly
pure populations of CD133+ and CD133- cells from metastatic melanoma, and that
these two populations have distinct characteristics not related to the cancer
stem cell phenotype. In vitro, gene set enrichment analysis indicated CD133+
cells were related to a proliferative phenotype, whereas CD133- cells were of an
invasive phenotype. However, in vivo, serial transplantation of CD133+ and CD133-
tumours over 7 generations showed that both populations were equally able to
initiate and propagate tumours. Despite this, both populations remained
phenotypically distinct, with CD133- cells only able to express CD133 in vivo and
not in vitro. Loss of CD133 from the surface of a CD133+ cell was observed in
vitro and in vivo, however CD133- cells derived from CD133+ retained the CD133+
phenotype, even in the presence of signals from the tumour microenvironment.
CONCLUSION: We show for the first time the necessity of iterative sorting to
isolate pure marker-positive and marker-negative populations for comparative
studies, and present evidence that despite CD133+ and CD133- cells being equally
tumourigenic, they display distinct phenotypic differences, suggesting CD133 may
define a distinct lineage in melanoma.
PMID- 27613606
TI - Traumatic neuroma of the superficial peroneal nerve in a patient: a case report
and review of the literature.
AB - BACKGROUND: Traumatic neuromas are rare benign tumors, which are common in trauma
or post-operation and accompanied with obvious symptoms of pain. This study will
show the superficial peroneal nerve neuroma occurring after resection of
hemangioma. CASE PRESENTATION: A 44-year-old male had an operation of the right
leg cavernous hemangioma resection in 1995. Half a year after the operation, pain
around the wound appeared and gradually aggravated. The patient had the lesion
exploration resection in 2013, and the pathological result showed traumatic
neuroma. Within half a year of the second operation, severe pain showed up again,
so neuroma resection proceeded in May 2015. The postoperative pathological and
immunohistochemical results showed traumatic neuroma. According to the
postoperative follow-up, there were no symptoms of pain appearing again.
LITERATURE REVIEW: The pain is obvious, and B ultrasonography is the most
efficient way to find neuromas. Both conservative and operative therapy have
their advantages and disadvantages. CONCLUSIONS: There remain many unanswered
questions in relation to the treatment of traumatic neuromas, and further
research is required, although we have already had adequate understanding of
traumatic neuromas.
PMID- 27613607
TI - Intravascular haemolysis with haemoglobinuria in a splenectomized patient with
severe Plasmodium knowlesi malaria.
AB - BACKGROUND: Haemoglobinuria is an uncommon complication of severe malaria,
reflecting acute intravascular haemolysis and potentially leading to acute kidney
injury. It can occur early in the course of infection as a consequence of a high
parasite burden, or may occur following commencement of anti-malarial treatment.
Treatment with quinine has been described as a risk factor; however the syndrome
may also occur following treatment with intravenous artesunate. In Malaysia,
Plasmodium knowlesi is the most common cause of severe malaria, often associated
with high parasitaemia. Asplenic patients may be at additional increased risk of
intravascular haemolysis. CASE PRESENTATION: A 61 years old asplenic man was
admitted to a tertiary referral hospital in Sabah, Malaysia, with severe knowlesi
malaria characterized by hyperparasitaemia (7.9 %), jaundice, respiratory
distress, metabolic acidosis, and acute kidney injury. He was commenced on
intravenous artesunate, but1 day later developed haemoglobinuria, associated with
a 22 % reduction in admission haemoglobin. Additional investigations, including a
cell-free haemoglobin of 10.2 * 10(5) ng/mL and an undetectable haptoglobin,
confirmed intravascular haemolysis. The patient continued on intravenous
artesunate for a total of 48 h prior to substitution with artemether
lumefantrine, and made a good recovery with resolution of his haemoglobinuria and
improvement of his kidney function by day 3. CONCLUSIONS: An asplenic patient
with hyperparasitaemic severe knowlesi malaria developed haemoglobinuria after
treatment with intravenous artesunate. There are plausible mechanisms for
increased haemolysis with hyperparasitaemia, and following both splenectomy and
artesunate. Although in this case the patient made a rapid recovery, knowlesi
malaria patients with this unusual complication should be closely monitored for
potential deterioration.
PMID- 27613608
TI - Transient receptor potential cation 3 channel regulates melanoma proliferation
and migration.
AB - Melanoma has an extremely poor prognosis due to its rapidly progressive and
highly metastatic nature. Several therapeutic drugs have recently become
available, but are effective only against melanoma with specific BRAF gene
mutation. Thus, there is a need to identify other target molecules. We show here
that Transient receptor potential, canonical 3 (TRPC3) is widely expressed in
human melanoma. We found that pharmacological inhibition of TRPC3 with a pyrazole
compound, Pyr3, decreased melanoma cell proliferation and migration. Similar
inhibition was observed when the TRPC3 gene was silenced with short-hairpin RNA
(shRNA). Pyr3 induced dephosphorylation of signal transducer and activator of
transcription (STAT) 5 and Akt. Administration of Pyr3 (0.05 mg/kg) to mice
implanted with human melanoma cells (C8161) significantly inhibited tumor growth.
Our findings indicate that TRPC3 plays an important role in melanoma growth, and
may be a novel target for treating melanoma in patients.
PMID- 27613609
TI - Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and
the growth of HER2+ breast cancer.
AB - PURPOSE: Human epidermal growth factor receptor-2 (HER2) has been implicated in
the progression of multiple tumor types, including breast cancer, and many
downstream effectors of HER2 signaling are primary regulators of cellular
metabolism, including Ras and Akt. A key downstream metabolic target of Ras and
Akt is the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 isozyme
(PFKFB3), whose product, fructose-2,6-bisphosphate (F26BP), is a potent
allosteric activator of a rate-limiting enzyme in glycolysis, 6-phosphofructo-1
kinase (PFK-1). We postulate that PFKFB3 may be regulated by HER2 and contribute
to HER2-driven tumorigenicity. METHODS: Immunohistochemistry and Kaplan-Meier
analysis of HER2+ patient samples investigated the relevance of PFKFB3 in HER2+
breast cancer. In vitro genetic and pharmacological inhibition of PFKFB3 was
utilized to determine effects on HER2+ breast cancer cells, while HER2 antagonist
treatment assessed the mechanistic regulation on PFKFB3 expression and glucose
metabolism. Administration of a PFKFB3 inhibitor in a HER2-driven transgenic
breast cancer model evaluated this potential therapeutic approach in vivo.
RESULTS: PFKFB3 is elevated in human HER2+ breast cancer and high PFKFB3
transcript correlated with poorer progression-free (PFS) and distant metastatic
free (DFMS) survival. Constitutive HER2 expression led to elevated PFKFB3
expression and increased glucose metabolism, while inhibition of PFKFB3
suppressed glucose uptake, F26BP, glycolysis, and selectively decreased the
growth of HER2-expressing breast cancer cells. In addition, treatment with
lapatinib, an FDA-approved HER2 inhibitor, decreased PFKFB3 expression and
glucose metabolism in HER2+ cells. In vivo administration of a PFKFB3 antagonist
significantly suppressed the growth of HER2-driven breast tumors and decreased
18F-2-deoxy-glucose uptake. CONCLUSIONS: Taken together, these data support the
potential clinical utility of PFKFB3 inhibitors as chemotherapeutic agents
against HER2+ breast cancer.
PMID- 27613610
TI - Sexual function in young women with type 1 diabetes: the METRO study.
AB - PURPOSE: The aim of this study was to evaluate the prevalence and risk factors
associated with female sexual dysfunction (FSD) in young women with type 1
diabetes treated with different intensive insulin regimens. METHODS: Type 1
diabetic women aged 18-35 years were included in this study if they had stable
couple relationship and no oral contraceptive use. All women were asked to
complete the Female Sexual Function Index (FSFI) and other validated multiple
choice questionnaires assessing sexual-related distress (Female Sexual Distress
Scale, FSDS), quality of life (SF-36 Health Survey), physical activity
(International Physical Activity Questionnaire), depressive symptoms (Zung Self
Rating Depression Scale, SRDS) and diabetes-related problems (Diabetes
Integration Scale ATT-19). FSD was diagnosed according to a FSFI score higher
than 26.55 and a FSDS score lower than 15. RESULTS: The overall prevalence of FSD
in diabetic and control women was 20 and 15 %, respectively (P = 0.446). Compared
with the continuous subcutaneous insulin infusion group and control women,
diabetic women on multiple daily injections (MDI) had lower global FSFI score (P
= 0.007), FSDS score (P = 0.045) and domains such as arousal (P = 0.006),
lubrication and satisfaction scores (P < 0.001 for both). In the multiple
regression analysis, only the mental component summary (P = 0.047) and the SRDS
score (P = 0.042) were independent predictors of FSFI score in the overall
diabetic women. CONCLUSION: Young women with type 1 diabetes wearing an insulin
pump show a prevalence of sexual dysfunction similar to that of healthy age
matched women, but sexual function was significantly impaired in diabetic women
on MDI therapy. Depression and the mental health status were independent
predictors for FSD in diabetic women.
PMID- 27613611
TI - DNA methylation profiles of diverse Brachypodium distachyon align with underlying
genetic diversity.
AB - DNA methylation, a common modification of genomic DNA, is known to influence the
expression of transposable elements as well as some genes. Although commonly
viewed as an epigenetic mark, evidence has shown that underlying genetic
variation, such as transposable element polymorphisms, often associate with
differential DNA methylation states. To investigate the role of DNA methylation
variation, transposable element polymorphism, and genomic diversity, whole-genome
bisulfite sequencing was performed on genetically diverse lines of the model
cereal Brachypodium distachyon Although DNA methylation profiles are broadly
similar, thousands of differentially methylated regions are observed between
lines. An analysis of novel transposable element indel variation highlighted
hundreds of new polymorphisms not seen in the reference sequence. DNA methylation
and transposable element variation is correlated with the genome-wide amount of
genetic variation present between samples. However, there was minimal evidence
that novel transposon insertions or deletions are associated with nearby
differential methylation. This study highlights unique relationships between
genetic variation and DNA methylation variation within Brachypodium and provides
a valuable map of DNA methylation across diverse resequenced accessions of this
model cereal species.
PMID- 27613612
TI - Chemical shift assignments of nsp7alpha from porcine reproductive and respiratory
syndrome virus.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative
agent of porcine reproductive and respiratory syndrome, a destructive disease of
swine. PRRSV has a single strand positive-sense RNA genome which contains at
least ten open reading frames, of these, ORF1a and ORF1b encode polyproteins pp1a
and pp1ab. Subsequently, pp1a is cleaved into ten nonstructural proteins,
including nonstructural protein 7alpha and 7beta (nsp7alpha and 7beta), the
internal cleavage products of a conserved nonstructural protein nsp7. Nsp7 plays
a role in provoking the humoral immune system into producing anti-nsp7 antibodies
which can be highly and persistently expressed in PRRSV-infected swine. However,
the functions of nsp7alpha and 7beta remain unknown. Western blot and
radioimmunoprecipitation analysis of the two proteins showed that only cleaved
nsp7alpha was detectable and cleaved nsp7beta was not detected in the infected
cells. Here, we reported the (1)H, (13)C and (15)N resonance assignment of
nsp7alpha from PRRSV as a basis for further structural and functional studies.
PMID- 27613613
TI - Influence of increment thickness on dentin bond strength and light transmission
of composite base materials.
AB - OBJECTIVES: Bulk-fill resin composites (BFCs) are gaining popularity in
restorative dentistry due to the reduced chair time and ease of application. This
study aimed to evaluate the influence of increment thickness on dentin bond
strength and light transmission of different BFCs and a new discontinuous fiber
reinforced composite. MATERIALS AND METHODS: One hundred eighty extracted sound
human molars were prepared for a shear bond strength (SBS) test. The teeth were
divided into four groups (n = 45) according to the resin composite used: regular
particulate filler resin composite: (1) G-aenial Anterior [GA] (control); bulk
fill resin composites: (2) Tetric EvoCeram Bulk Fill [TEBF] and (3) SDR; and
discontinuous fiber-reinforced composite: (4) everX Posterior [EXP]. Each group
was subdivided according to increment thickness (2, 4, and 6 mm). The irradiance
power through the material of all groups/subgroups was quantified (MARC(r) Resin
Calibrator; BlueLight Analytics Inc.). Data were analyzed using two-way ANOVA
followed by Tukey's post hoc test. RESULTS: SBS and light irradiance decreased as
the increment's height increased (p < 0.05), regardless of the type of resin
composite used. EXP presented the highest SBS in 2- and 4-mm-thick increments
when compared to other composites, although the differences were not
statistically significant (p > 0.05). Light irradiance mean values arranged in
descending order were (p < 0.05) EXP, SDR, TEBF, and GA. CONCLUSIONS: As
increment thickness increased, the light transmission decreased for all tested
resin composites. Discontinuous fiber-reinforced composite showed the highest
value of curing light transmission, which was also seen in improved bonding
strength to the underlying dentin surface. CLINICAL RELEVANCE: Discontinuous
fiber-reinforced composite can be applied safely in bulks of 4-mm increments same
as other bulk-fill composites, although, in 2-mm thickness, the investigated
composites showed better performance.
PMID- 27613615
TI - A Phenylurea Cytokinin, CPPU, Elevated Reducing Sugar and Correlated to
Andrographolide Contents in Leaves of Andrographis paniculata (Burm. F.) Wall. Ex
Nees.
AB - Cytokinins are phytohormones that play multiple roles to control plant growth and
development. In this study, leaf biomass and the production of andrographolide
compounds in a medicinal plant Andrographis paniculata were significantly
increased after exogenously treating with the synthetic cytokinin cytokinin-1-(2
chloro-4-pyridyl)-3-phenylurea (CPPU) at 0 (water), 5, or 10 mg L-1 and observed
the results for 24 h, 48 h, and 7 days of treatment. It was found that CPPU could
significantly enhance new axillary bud formation and further promote branching
4.6-5.6-fold higher, resulting in higher fresh weight (FW) and dry weight (DW)
than the control. Application of CPPU at 5 mg L-1 significantly promoted the
highest contents of total reducing sugar at 2.5-fold in leaves and at 1.5-fold in
roots. Although treatments of CPPU significantly affected the increasing contents
of chlorophyll and carotenoid (1.2-1.6-fold), CPPU at 10 mg L-1 slightly caused
leaf stress and chlorophyll reduction. Interestingly, 5 mg L-1 CPPU could enhance
andrographolide content, an active anti-infectious compound in Andrographis
paniculata (2.2-fold higher than the control) that reached the highest content at
24 h after treatment. This study suggested that CPPU should be suitable for field
application to promote leaf yields and induce the production of useful
pharmaceutical compounds in Andrographis paniculata.
PMID- 27613616
TI - Selection and Identification of Chloramphenicol-Specific DNA Aptamers by Mag
SELEX.
AB - Chloramphenicol (CAP) has been widely used to treat bacterial infections in
livestock and aquatic animals. To reduce the risk of CAP residues, an efficient
technology to rapidly detect CAP residues in animal-sourced food is expressly
needed. In this study, magnetic bead-based systematic evolution of ligands by
exponential enrichment (Mag-SELEX) strategy was performed to select and identify
CAP-specific single-stranded DNA (ssDNA) aptamers from a random oligonucleotide
library. After nine rounds of selection, five potential ssDNA aptamers were
selected. Low homology indicated that they might belong to different families. To
identify an aptamer with the highest affinity for CAP, the dissociation constant
(K d) values of these selected aptamers were determined. The lowest K d values of
two potential aptamers (i.e., No. 4 and No. 5) were, respectively, 0.10162 +/-
0.0111 and 0.03224 +/- 0.00819 MUM, which were much lower than previously
reported lowest K d value (i.e., 0.766 MUM) of CAP aptamer. Moreover, compared
with No. 4, aptamer No. 5 had higher binding rate, which is quite different among
those with CAP and with CAP's structural analogs (i.e., thiamphenicol (TAP) and
florfenicol (FF)). These results indicated that the potential aptamer No. 5 with
highest specificity and affinity for CAP would be an ideal aptamer for future
detection of residual CAP in animal-sourced food.
PMID- 27613614
TI - Antibiotic use in acute pancreatitis: An audit of current practice in a tertiary
centre.
AB - INTRODUCTION: Intravenous antibiotic prophylaxis is not recommended in acute
pancreatitis. According to current international guidelines antibiotics together
with further intervention should be considered in the setting of infected
necrosis. Appropriate antibiotic therapy particularly avoiding over-prescription
is important. This study examines antibiotic use in acute pancreatitis in a
tertiary centre using the current IAP/APA guidelines for reference. METHODS: Data
were collected on a consecutive series of patients admitted with acute
pancreatitis over a 12 month period. Data were dichotomized by patients admitted
directly to the centre and tertiary transfers. Information was collected on
clinical course with specific reference to antibiotic use, episode severity,
intervention and outcome. RESULTS: 111 consecutive episodes of acute pancreatitis
constitute the reported population. 31 (28%) were tertiary transfers. Overall 65
(58.5%) patients received antibiotics. Significantly more tertiary transfer
patients received antibiotics. Mean person-days of antibiotic use was 23.9 (sd
29.7) days in the overall study group but there was significantly more use in the
tertiary transfer group as compared to patients having their index admission to
the centre (40.9 sd 37.1 vs 10.2 sd 8.9; P < 0.005). Thirty four (44%) of
patients with clinically mild acute pancreatitis received antibiotics.
CONCLUSIONS: There is substantial use of antibiotics in acute pancreatitis, in
particular in patients with severe disease. Over-use is seen in mild acute
pancreatitis. Better consideration must be given to identification of prophylaxis
or therapy as indication. In relation to repeated courses of antibiotics in
severe disease there must be clear indications for use.
PMID- 27613617
TI - Function Analysis of Caffeoyl-CoA O-Methyltransferase for Biosynthesis of Lignin
and Phenolic Acid in Salvia miltiorrhiza.
AB - In this study, we cloned a full-length cDNA and the genomic DNA sequence of
SmCCoAOMT (GenBank ID JQ007585) from Salvia miltiorrhiza. The 744-bp open-reading
frame encodes a protein of 247 amino acids that shares 95 % similarity with one
in Vitis vinifera. Real-time quantitative PCR analysis revealed that SmCCoAOMT is
most highly expressed in the stems and can be induced by methyl jasmonate (MeJA)
and XC-1 treatment. To evaluate its function in vivo, we generated RNA
interference transgenic plants through Agrobacterium tumefaciens-mediated gene
transfer. Compared with untransformed control plants, the transgenics had
significantly less lignin and the expression of lignin-biosynthetic genes SmCCR
and SmCOMT was depressed. In 90-day-old roots from plants of transgenic line M5,
accumulations of rosmarinic acid and salvianolic acid B (Sal B) were greatly
reduced by 0.89- and 0.69-fold, respectively. This low-Sal B phenotype was stable
in the roots, with the level of accumulation being approximately 43.58 mg g-1 dry
weight, which was 52 % of the amount measured in the untransformed control. Our
results suggest that SmCCoAOMT is involved in lignin biosynthesis and affects the
accumulation of phenolic acids. This study also provides potential guidance for
using lignin-related genes to genetically engineer Salvia miltiorrhiza.
PMID- 27613620
TI - Maresin 1 Maintains the Permeability of Lung Epithelial Cells In Vitro and In
Vivo.
AB - Previous reports showed that Maresin 1 (MaR1) possessed organ protection effects
and could attenuate acute lung injury. Here, we aim to figure out whether MaR1
can maintain the permeability of lung epithelial cells by regulating the
expression of tight junction protein during lung injury. Monolayer of murine lung
epithelial cells was stimulated by lipopolysaccharide (LPS) with or without MaR1
and the permeability was evaluated. The expression of Claudin-1 and ZO-1 in lung
epithelial cells was analyzed by immunofluorescence staining and western
blotting. MaR1 was given to the mice after LPS induced acute lung injury. The
permeability of lung was assessed by Evans Blue extravasation, lung wet/dry ratio
and protein concentration in bronchoalveolar lavage fluid. Lung injury score was
also evaluated. The expression of Claudin-1 and ZO-1 in the lung was analyzed by
immunofluorescence staining. Results showed that MaR1 maintained the permeability
of lung epithelial cells and upregulated the expression of Claudin-1 and ZO-1
after LPS stimulation. In acute lung injury mice, MaR1 upregulated the expression
of Claudin-1 and ZO-1, decreased lung permeability, and reduced lung injury. In
summary, this study suggests that MaR1 can maintain the permeability of lung
epithelial cells by upregulating the expression of Claudin-1 and ZO-1 in acute
lung injury.
PMID- 27613619
TI - Towards a Better Treatment Option for Parkinson's Disease: A Review of Adult
Neurogenesis.
AB - The motor symptoms of Parkinson's disease (PD) are caused by degeneration of
dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of midbrain.
Given the fact that current treatment options are mostly symptomatic and based on
increasing DA level in the nigrostriatal system, it is generally believed the
most effective and long-lasting treatment for PD motor symptoms will be replacing
SNc DA cells, either by endogenous repair (i.e. neurogenesis) or cell
transplantation. While cell transplantation is hindered by failure of acquisition
and maintenance of the DA phenotype by transplanted cells, hope rests upon non
invasive cell replacement therapy (CRT) with endogenous neural stem cells, which
have the potential to give rise to new neurons including DA neurons.
Understanding underlying mechanisms and signalling pathways of neurogenesis in
the adult brain could shed light on obstacles to achieve effective CRTs and
better treatments for PD. This paper first reviews different therapeutic
strategies in context of PD along with their advantages and disadvantages
followed by an extensive review of adult neurogenesis.
PMID- 27613618
TI - Disease-Toxicant Interactions in Parkinson's Disease Neuropathology.
AB - Human disease commonly manifests as a result of complex genetic and environmental
interactions. In the case of neurodegenerative diseases, such as Parkinson's
disease (PD), understanding how environmental exposures collude with genetic
polymorphisms in the central nervous system to cause dysfunction is critical in
order to develop better treatment strategies, therapies, and a more cohesive
paradigm for future research. The intersection of genetics and the environment in
disease etiology is particularly relevant in the context of their shared
pathophysiological mechanisms. This review offers an integrated view of disease
toxicant interactions in PD. Particular attention is dedicated to how mutations
in the genes SNCA, parkin, leucine-rich repeat kinase 2 (LRRK2) and DJ-1, as well
as dysfunction of the ubiquitin proteasome system, may contribute to PD and how
exposure to heavy metals, pesticides and illicit drugs may further the
consequences of these mutations to exacerbate PD and PD-like disorders. Although
the toxic effects induced by exposure to these environmental factors may not be
the primary causes of PD, their mechanisms of action are critical for our current
understanding of the neuropathologies driving PD. Elucidating how environment and
genetics collude to cause pathogenesis of PD will facilitate the development of
more effective treatments for the disease. Additionally, we discuss the
neuroprotection exerted by estrogen and other compounds that may prevent PD and
provide an overview of current treatment strategies and therapies.
PMID- 27613621
TI - Caveolin-1 Promotes the Imbalance of Th17/Treg in Patients with Chronic
Obstructive Pulmonary Disease.
AB - The imbalance of Th17/Treg cells plays an important role in the pathogenesis of
chronic obstructive pulmonary disease (COPD). Caveolin-1 (Cav-1) has been
regarded as a potential critical regulatory protein in pathological mechanisms of
chronic inflammatory respiratory diseases. Therefore, we investigated whether the
loss of Cav-1 is involved in the homeostasis of Th17/Treg cells in COPD. We
examined the expressions of plasma Cav-1 and circulating Th17, Treg cells, and
the related cytokines in patients with COPD. Enzyme-linked immunosorbent assay
(ELISA) analyses showed a significant reduction of plasma Cav-1 levels in
patients with stable COPD (SCOPD) and acutely exacerbated COPD (AECOPD) compared
to smokers without COPD. This loss was associated with an increase in frequency
of Treg and decreased in frequency of Th17 cells. To further identify the role of
Cav-1, we studied the effects of Cav-1 overexpression or downregulation on
frequencies of Treg and Th17 cells in peripheral blood mononuclear cells (PBMCs)
from subjects. Interestingly, small interfering RNA (siRNA) downregulation of Cav
1 was accompanied by an augmentation of Treg and reduction of Th17 expression.
Together, our study demonstrated that the loss of Cav-1 contributed to the
imbalance of Th17/Treg cells in patients with COPD.
PMID- 27613622
TI - Pelvic floor muscle training in groups versus individual or home treatment of
women with urinary incontinence: systematic review and meta-analysis.
AB - INTRODUCTION AND HYPOTHESIS: Urinary Incontinence (UI) in women is a condition
that becomes more common with age. Pelvic floor muscle training (PFMT) is
recommended as a first option of treatment for women with symptoms of stress
urinary incontinence (SUI), mixed urinary incontinence (MUI), and for some with
symptoms of urge urinary incontinence (UUI). PFMT can be performed in groups,
individually, and at home, and there is no consensus as to which of the
approaches is more efficient for the conservative treatment of UI. The objective
was to perform a systematic review comparing the effects of group PFMT vs
individual or home training in the treatment of women with UI. METHODS:
Cochrane's recommendations for systematic reviews were followed. The inclusion
criteria were that the studies had been carried out in adult women who suffered
from UI and who underwent PFMT in a group. RESULTS: Ten studies that fit the
criteria previously mentioned were included in this systematic review. The meta
analysis showed that there was no difference when comparing PFMT in groups vs
individual PFMT. However, when comparing PFMT in groups vs PFMT at home, the
group intervention was more efficient in the treatment of UI. CONCLUSION: PFMT is
an efficient technique for the improvement of the symptoms of female UI. When
PFMT was supervised by a physiotherapist, no significant difference was noted
when comparing group with individual approaches.
PMID- 27613623
TI - Residual defects after repair of obstetric anal sphincter injuries and pelvic
floor muscle strength are related to anal incontinence symptoms.
AB - INTRODUCTION AND HYPOTHESIS: The aim was to analyze the correlation between
residual anal sphincter (AS) defects and pelvic floor muscle (PFM) strength on
anal incontinence (AI) in patients with a history of obstetric AS injuries
(OASIS). METHODS: From September 2012 to February 2015, an observational study
was conducted on a cohort of females who underwent repair of OASIS intrapartum.
The degree of OASIS was scored intrapartum according to Sultan's classification.
Participants were assessed at 6 months postpartum. Incontinence symptoms were
evaluated using Wexner's score and PFM strength using the Modified Oxford Scale
(MOS). 3D-endoanal ultrasound was performed to classify AS defects according to
Starck's system. Correlation between Sultan's and Starck's classifications was
calculated using Cohen's kappa and Spearman's rho (Rs) test. The impact of
residual AS defects and PFM strength on AI was analyzed using a multiple
regression model. RESULTS: A total of 95 women were included in the study. Good
correlation (kappa= 0.72) was found between Sultan's and Starck's
classifications. Significant positive correlation was observed between Wexner's
score and both Sultan's (p = 0.023, Rs =0.212) and Starck's (p < 0.001, Rs
=0.777) scores. The extent of the residual AS defect was the most relevant factor
correlating with AI symptoms. In patients with severe AS injuries, higher MOS
values were associated with lower Wexner's score. CONCLUSIONS: The degree of AS
tear measured intrapartum was the most important factor related to AI after
primary repair of OASIS. PFM strength was associated with lower incontinence
symptoms in the postpartum period.
PMID- 27613624
TI - Influence of filtration velocity on DON variation in BAF for micropolluted
surface water treatment.
AB - Biological aerated filters (BAFs) are widely used for the treatment of
micropolluted surface water. However, the biological process produces dissolved
organic nitrogen (DON), which, as precursors of nitrogenous disinfection by
products, pose potential threats to drinking water safety. Therefore, to control
DON in BAF effluent, it is necessary to study the influence of BAF operation
parameters on DON production. In this study, the influence of filtration velocity
in a BAF on DON production was investigated. Under different filtration velocity
(0.5, 2, and 4 m/h) conditions, profiles of DON concentrations along the media
layer were measured. The profile at a filtration velocity of 0.5 m/h showed a
decreasing trend, and the ones under filtration velocities of 2 and 4 m/h
fluctuated in a small range (from 0.1 to 0.4 mg/L). Moreover, the relatively high
filtration velocities of 2 and 4 m/h resulted in a lower level of DON
concentration. Additionally, 3D excitation-emission matrix fluorescence
spectroscopy was used to characterize DON. It is found that the patterns of DON
at a relatively high filtration velocity condition (4 m/h) were obviously
different from the ones under low filtration velocity conditions (0.5 and 2 m/h).
PMID- 27613625
TI - Endogenous trans-zeatin content in plants with different metal-accumulating
ability: a field survey.
AB - A field survey was conducted to evaluate soil metal pollution and endogenous
trans-zeatin content in the leaves of plants growing at six sites in a metal
polluted area located in Gejiu, Yunnan, China. Five plant species were collected,
and the physicochemical properties and concentrations of five metals in the soil
were analyzed. The trans-zeatin content in plant leaves was measured by high
performance liquid chromatography. Based on the Nemerow pollution index, the six
sites were classified into four levels of pollution (i.e., low, medium, high, and
severely high). The degree of soil metal pollution was cadmium (Cd) > arsenic
(As) > lead (Pb) > zinc (Zn) > copper (Cu). The leaf trans-zeatin content in
Pteris vittata (an arsenic hyperaccumulator) increased significantly by 98.6 % in
soil with a severely high level of pollution compared with soil at a low level of
pollution. However, in non-hyperaccumulators Bidens pilosa var. radiata and
Ageratina adenophora, a significant decrease in leaf trans-zeatin content of 35.6
and 87.6 %, respectively, was observed. The leaf trans-zeatin content in
Artemisia argyi also decreased significantly by 73.6 % in high metal-polluted
soil compared with that in medium metal-polluted soil. Furthermore, significant
correlations were observed between leaf trans-zeatin content in Pteris vittata
and As, Pb, and Cd concentrations in the soil; however, either no correlation or
a negative one was observed in the other plant species. Therefore, a high content
of trans-zeatin in the leaves of Pteris vittata may play an important role in its
normal growth and tolerance to metals.
PMID- 27613626
TI - Long trend reduction of phosphorus wastewater loading in the Seine: determination
of phosphorus speciation and sorption for modeling algal growth.
AB - The lower Seine River is severely affected by the release of the treated
wastewater from the 12 million inhabitants of the Paris agglomeration. Whereas
urban effluents were the major source of phosphorus pollution in the late 1980s,
the ban on polyphosphates from detergents in 1991 considerably reduced the
phosphorus (P) loading to the Seine River and was followed in 2000 by the
implementation of phosphorus treatment in the largest wastewater treatment plant
of Paris conurbation (Seine Aval). Phosphorus discharged to the rivers from
domestic wastewater was reduced by 80 %, significantly decreasing phytoplankton
biomass in the large branches of the Seine River. Considering that phosphorus
treatment (the use of ferric salts in the P treatment line) might change the
adsorption of ortho-phosphates on suspended matter, we experimentally studied
again their sorption processes in these new conditions. We found parameters of
the Langmuir equation (Pac = 0.003 mgP mgSS-1; Kps = 0.04 mgP L-1) that
significantly differed from the values previously considered for modeling of the
whole Seine, especially for Kps (Pac = 0.0055 mgP mgSS-1; Kps = 0.7 mgP L-1).
Using the Seneque-Rivertrahler modeling approach, we showed a better agreement
between P observations and simulations with the new P sorption parameters, with
slight effect on the simulation of the development of phytoplankton in the water
column.
PMID- 27613627
TI - Cross-sectional biomonitoring study of pesticide exposures in Queensland,
Australia, using pooled urine samples.
AB - A range of pesticides are available in Australia for use in agricultural and
domestic settings to control pests, including organophosphate and pyrethroid
insecticides, herbicides, and insect repellents, such as N,N-diethyl-meta
toluamide (DEET). The aim of this study was to provide a cost-effective
preliminary assessment of background exposure to a range of pesticides among a
convenience sample of Australian residents. De-identified urine specimens
stratified by age and sex were obtained from a community-based pathology
laboratory and pooled (n = 24 pools of 100 specimens). Concentrations of urinary
pesticide biomarkers were quantified using solid-phase extraction coupled with
isotope dilution high-performance liquid chromatography-tandem mass spectrometry.
Geometric mean biomarker concentrations ranged from <0.1 to 36.8 ng/mL for
organophosphate insecticides, <0.1 to 5.5 ng/mL for pyrethroid insecticides, and
<0.1 to 8.51 ng/mL for all other biomarkers with the exception of the DEET
metabolite 3-diethylcarbamoyl benzoic acid (4.23 to 850 ng/mL). We observed no
association between age and concentration for most biomarkers measured but noted
a "U-shaped" trend for five organophosphate metabolites, with the highest
concentrations observed in the youngest and oldest age strata, perhaps related to
age-specific differences in behavior or physiology. The fact that concentrations
of specific and non-specific metabolites of the organophosphate insecticide
chlorpyrifos were higher than reported in USA and Canada may relate to
differences in registered applications among countries. Additional biomonitoring
programs of the general population and focusing on vulnerable populations would
improve the exposure assessment and the monitoring of temporal exposure trends as
usage patterns of pesticide products in Australia change over time.
PMID- 27613628
TI - Improving the Fenton process by visible LED irradiation.
AB - The effect of irradiation with visible light-emitting diode (LED) light on the
efficiency of Fenton oxidation is investigated using phenol as the target
compound (100 mg/L). The H2O2 dose and temperature are tested as operating
variables with the aim of minimizing consumption of the reagents. At 50 degrees
C, 10 mg/L Fe2+, and 60 % of the stoichiometric H2O2 amount, phenol was
completely oxidized into CO2, H2O, and short chain organic acids, with oxalic
acid completely degraded. Up to 95 % mineralization was achieved. This high
efficiency can be attributed to the effect of LED radiation on the
quinones/Fe2+/Fe3+/H2O2 cycle, which significantly increases the reaction rate,
as well as on the photodecomposition of the iron complexes formed along the
oxidation process, which also enhanced mineralization.
PMID- 27613629
TI - Comparative study of dioxin contamination from forest soil samples (BZE II) by
mass spectrometry and EROD bioassay.
AB - Dioxins and dioxin-like compounds can be analyzed by bioanalytical screening
methods to evaluate their biotoxicity. In vitro bioassays, based on 7
ethoxyresorufin-O-deethylase (EROD) and the activity of cytochrome P450 1A1 and
the aryl hydrogen receptor (AhR) pathway, are employed for the evaluation of
bioanalytical equivalents (BEQ) of polychlorinated dibenzo-p-dioxins (PCDDs),
polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) from
a wide variety of sample matrices. Here, we present the evaluation of 11 humic
soil samples derived from forest stands across Germany and a comparison of the
BEQ values against toxic equivalents (TEQ, PCDD/Fs+PCBs) derived by chemical
analysis. BEQ values ranged from 8.8 to 34.1 while TEQ values from 13.9 to 60.5
pg/g dry weight. Additional two subsequent mineral layers were analyzed to
identify the BEQ/TEQ gradient vertically, showing a TEQ decrease of 85.1 and 93.8
% from the humic to the first and second mineral layers, respectively. For BEQ
values, a decrease as well as an increase was detected. BEQ measurements were
performed with and without sample clean-up. Omitting clean-up revealed about 20
times increased BEQ values presumably due to non-persistent bioactive compounds
not detected by chemical analysis. The results we present suggest that the EROD
assay can be used for the screening of large sample quantities for the
identification of samples showing dioxin and dioxin-like contaminations even at
low levels, which can then be further analyzed by chemical analysis to identify
the congener composition. The study also shows that EROD results give a
qualitative image of the contamination. EROD seems to be interfered with cross
contaminants specifically for soils with high biological activity as forest
layers.
PMID- 27613630
TI - The influence of the scale of mining activity and mine site remediation on the
contamination legacy of historical metal mining activity.
AB - Globally, thousands of kilometres of rivers are degraded due to the presence of
elevated concentrations of potentially harmful elements (PHEs) sourced from
historical metal mining activity. In many countries, the presence of contaminated
water and river sediment creates a legal requirement to address such problems.
Remediation of mining-associated point sources has often been focused upon
improving river water quality; however, this study evaluates the contaminant
legacy present within river sediments and attempts to assess the influence of the
scale of mining activity and post-mining remediation upon the magnitude of PHE
contamination found within contemporary river sediments. Data collected from four
exemplar catchments indicates a strong relationship between the scale of
historical mining, as measured by ore output, and maximum PHE enrichment factors,
calculated versus environmental quality guidelines. The use of channel slope as a
proxy measure for the degree of channel-floodplain coupling indicates that
enrichment factors for PHEs in contemporary river sediments may also be the
highest where channel-floodplain coupling is the greatest. Calculation of a
metric score for mine remediation activity indicates no clear influence of the
scale of remediation activity and PHE enrichment factors for river sediments. It
is suggested that whilst exemplars of significant successes at improving post
remediation river water quality can be identified; river sediment quality is a
much more long-lasting environmental problem. In addition, it is suggested that
improvements to river sediment quality do not occur quickly or easily as a result
of remediation actions focused a specific mining point sources. Data indicate
that PHEs continue to be episodically dispersed through river catchments hundreds
of years after the cessation of mining activity, especially during flood flows.
The high PHE loads of flood sediments in mining-affected river catchments and the
predicted changes to flood frequency, especially, in many river catchments,
provides further evidence of the need to enact effective mine remediation
strategies and to fully consider the role of river sediments in prolonging the
environmental legacy of historical mine sites.
PMID- 27613631
TI - Early Onset of Ocular Neovascularization After Hyperbaric Oxygen Therapy in a
Patient With Central Retinal Artery Occlusion.
AB - Central retinal artery occlusion (CRAO) is an infarction to the retina that
results in acute, frequently severe vision loss. Long-term complications such as
ocular neovascularization (ONV) can occur and result in neovascular glaucoma and
vitreous hemorrhage. Recent studies have explored acute hyperbaric oxygen (HBO)
therapy as a promising treatment for CRAO to improve long-term vision potential;
however, its effects on CRAO complications have not been well characterized. This
study was conducted to better characterize the effects of HBO therapy on
complications from CRAO. We present a unique case of ONV in an eye within 1 month
after successfully completing acute HBO therapy for a CRAO, highlighting the
importance of routine monitoring in this unique population.
PMID- 27613632
TI - The efficacy and safety of burr-hole craniotomy without continuous drainage for
chronic subdural hematoma and subdural hygroma in children under 2 years of age.
AB - PURPOSE: Various treatment modalities have been used in the management of chronic
subdural hematoma and subdural hygroma (CSDH/SDHy) in children. However, few
studies have examined burr-hole craniotomy without continuous drainage in such
cases. Here, we retrospectively evaluated the efficacy and safety of burr-hole
craniotomy without continuous drainage for CSDH/SDHy in children under 2 years
old. We also aimed to determine the predictors of CSDH/SDHy recurrence. METHODS:
We conducted a retrospective chart review of 25 children under 2 years old who
underwent burr-hole craniotomy without continuous drainage for CSDH/SDHy at a
pediatric teaching hospital over a 10-year period. We analyzed the relationship
between CSDH/SDHy recurrence and factors such as abusive head trauma, laterality
of CSDH/SDHy, and subdural fluid collection type (hematoma or hygroma). RESULTS:
CSDH/SDHy recurred in 5 of the 25 patients (20 %), requiring a second operation
at an average of 0.92 +/- 1.12 months after the initial procedure. The mean
follow-up period was 25.1 +/- 28.6 months. There were no complications related to
either operation. None of the assessed factors were statistically associated with
recurrence. CONCLUSIONS: Burr-hole craniotomy without continuous drainage for
CSDH/SDHy appears safe in children aged under 2 years and results in a relatively
low recurrence rate. No predictors of CSDH/SDHy recurrence were identified.
Advantages of this method include avoiding external subdural drainage-related
complications. However, burr-hole drainage may be more effective for CSDH, which
our data suggests is more likely to recur than SDHy, providing the procedure is
performed with specific efforts to reduce complications.
PMID- 27613633
TI - Segmental spinal dysgenesis: a report of early surgical intervention and outcome
in a 14-month-old child.
AB - Segmental spinal dysgenesis is a rare spinal deformity that is the result of
failure of formation resulting in some cases spondyloptosis and neurological
dysfunction usually at the thoracolumbar junction. There is little known
concerning surgical intervention and timing in these patients. The goal of this
case report is to present a case involving 14 months old diagnosed with segmental
spinal dysgenesis with stenosis at the thoracolumbar junction soon after birth,
treated with definitive posterior spinal fusion and subsequent follow-up.
PMID- 27613634
TI - Cerebral involvement in mitochondrial disorders on imaging.
PMID- 27613636
TI - Letter to the editor Re: Singh I et al.: growing skull fractures: guidelines for
early diagnosis and surgical management (2016).
PMID- 27613635
TI - Efficacy and safety of endoscopic third ventriculostomy and choroid plexus
cauterization for infantile hydrocephalus: a systematic review and meta-analysis.
AB - PURPOSE: Endoscopic third ventriculostomy/choroid plexus cauterization (ETV/CPC)
has gained popularity in its treatment of infantile hydrocephalus over the past
decade. In this manuscript, we perform a systematic review and meta-analysis to
determine the efficacy and safety of ETV/CPC, and to compare the procedural
outcomes between North American and sub-Saharan African cohorts. METHODS:
Systematic review was performed using four electronic databases and
bibliographies of relevant articles, with no language or date restrictions.
Cohort studies of participants undergoing ETV/CPC that reported outcome were
included using MOOSE guidelines. The outcome was time to repeat CSF diversion or
death. Forest plots were created for pooled mean and its 95 % CI of outcome and
morbidity. RESULTS: Of 78 citations, 11 retrospective reviews (with 524 total
participants) were eligible. Efficacy was achieved in 63 % participants at follow
up periods between 6 months and 8 years. Adverse events and mortality was
reported in 3.7 and 0.4 % of participants, respectively. Publication bias was
detected with respect to efficacy and morbidity of the procedure. A large
discrepancy in success was identified between ETV/CPC in six studies from sub
Saharan Africa (71 %), compared to three studies from North America (49 %).
CONCLUSIONS: The reported success of ETV/CPC for infantile hydrocephalus is
higher in sub-Saharan Africa than developed nations. Large long-term prospective
multi-center observational studies addressing patient-important outcomes are
required to further evaluate the efficacy and safety of this re-emerging
procedure.
PMID- 27613637
TI - Occipital cephalohematoma-a rare pathology.
PMID- 27613638
TI - Taenia crassiceps injection into the subarachnoid space of rats simulates
radiological and morphological features of racemose neurocysticercosis.
AB - PURPOSE: Neurocysticercosis is a major public health concern. Although its
eradication appears feasible, the disease remains endemic in developing countries
and has emerged again in Europe and in the USA. Basic studies on
neurocysticercosis are needed to better understand the pathophysiologic
mechanisms and, consequently, to improve treatment perspectives. Much has been
published on experimental parenchymal neurocysticercosis, but there are no
experimental models of racemose neurocysticercosis. METHODS: Cysts of Taenia
crassiceps were injected into the subarachnoid space of 11 rats. After 4 months,
magnetic resonance imaging (MRI) was performed to verify the occurrence of
ventricular dilatation and the distribution of cysts in the cerebrospinal fluid
compartments. The histologic assessment was done focusing on changes in the
ependyma, choroid plexus, and brain parenchyma. RESULTS: MRI and histologic
assessment confirmed the findings similar to those seen in human racemose
neurocysticercosis including enlargement of the basal cisterns, hydrocephalus,
and inflammatory infiltration through the ependyma and choroid plexus into
cerebrospinal fluid spaces. CONCLUSIONS: We developed a simple model of racemose
neurocysticercosis by injecting cysts of T. crassiceps into the subarachnoid
space of rats. This model can help understand the pathophysiologic mechanisms of
the disease.
PMID- 27613639
TI - A history of the autonomic nervous system: part I: from Galen to Bichat.
AB - INTRODUCTION: The development of our current understanding of the autonomic
nervous system has a rich history with many international contributors.
CONCLUSIONS: Although our thoughts of an autonomic nervous system arose with the
Greeks, the evolution and final understanding of this neural network would not be
fully realized until centuries later. Therefore, our current knowledge of this
system is based on hundreds of years of hypotheses and testing and was
contributed to by many historic figures.
PMID- 27613640
TI - Spontaneous involution of pediatric low-grade gliomas: high expression of
cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement
of the endocannabinoid system.
AB - BACKGROUND: Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain
tumors that correspond to the majority of CNS tumors in children. Notably, they
may exhibit spontaneous involution after subtotal surgical removal (STR). In this
study, we investigated molecular indicators of spontaneous involution in P-LGG.
METHODS: We performed an integrated molecular analysis including high throughput
gene expression (GE), microRNA (miRNA) expression data of primary, untreated
tumors from patients with P-LGG who underwent STR at our institution, with at
least 10 years follow-up. RESULTS: We identified a set of protein-coding genes
and miRNAs significantly differentially expressed in P-LGG that presented
spontaneous involution (involution-I) or without progression (stable-S) after STR
alone. The cannabinoid receptor 1 (CNR1 or CB1) gene (FC = 2.374; p value =
0.007) was at the top of the list and predicted to be regulated by hsa-miR-29b-3p
(FC = -2.353, p value = 0.0001). CNR1 also showed a trend to be higher expressed
in S/I by immunohistochemistry. CONCLUSIONS: The P-LGG, which remained stable or
that presented spontaneous involution after STR, showed significantly higher CNR1
expression at the time of diagnosis. We hypothesize that high expression levels
of CNR1 provide tumor susceptibility to the antitumor effects of circulating
endocannabinoids like anandamide, resulting in tumor involution. This
corroborates with reports suggesting that CNR1 agonists and activators of the
endocannabinoid system may represent therapeutic opportunities for children with
LGG. We also suggest that CNR1 may be a prognostic marker for P-LGG. This is the
first time spontaneous involution of P-LGG has been suggested to be induced by
endocannabinoids.
PMID- 27613641
TI - A history of the autonomic nervous system: part II: from Reil to the modern era.
AB - INTRODUCTION: The history of the study of the autonomic nervous system is rich.
At the beginning of the nineteenth century, scientists were beginning to more
firmly grasp the reality of this part of the human nervous system. CONCLUSIONS:
The evolution of our understanding of the autonomic nervous system has a rich
history. Our current understanding is based on centuries of research and trial
and error.
PMID- 27613643
TI - Diaphragm height varies with arm position: comparison between angiography and CT.
AB - PURPOSE: To investigate how elevation of the arms affects diaphragm height.
MATERIALS AND METHODS: We retrospectively reviewed angiography and computed
tomography (CT) portography data from 44 patients who were treated for
hepatocellular carcinoma at our institution from July 2013 to May 2014. Diaphragm
height was determined independently by two radiologists as the distance from the
upper edge of the first lumbar vertebra to the highest point of the right
diaphragm. The differences in height between angiography and CT images were
compared using a paired t-test. We also evaluated the influence of table height
and distance between X-ray tube and flat panel detector [source-image distance
(SID)] on a phantom model. RESULTS: Diaphragm height was higher on CT images
[mean +/- standard deviation (SD), 113.2 +/- 27.2 mm] than on angiography images
(105.5 +/- 27.8 mm; P < 0.001). Inter-rater correlation was excellent both in
angiography (R = 0.920; P < 0.001) and CT (R = 0.950; P < 0.001) measurements.
Table height and SID had no influence on diaphragm height measurements (P =
0.33). CONCLUSION: The diaphragm elevation was observed on CT with arm elevation
compared with angiography without arm elevation.
PMID- 27613642
TI - Glucocorticoids in the management of peritumoral brain edema: a review of
molecular mechanisms.
AB - Peritumoral brain edema (PTBE) is mediated by blood-brain barrier breakdown. PTBE
results from interstitial vasogenic brain edema due to vascular endothelial
growth factor and other inflammatory products of brain tumors. Glucocorticoids
(GCs) are the mainstay for treatment of PTBE despite significant systemic side
effects. GCs are thought to affect multiple cell types in the edematous brain.
Here, we review preclinical studies of GC effects on edematous brain and review
mechanisms underlying GC action on tumor cells, endothelial cells, and
astrocytes. GCs may reduce tumor cell viability and suppress vascular endothelial
growth factor (VEGF) production in tumor cells. Modulation of expression and
distribution of tight junction proteins occludin, claudin-5, and ZO-1 in
endothelial cells likely plays a central role in GC action on endothelial cells.
GCs may also have an effect on astrocyte angiopoietin production and limited
effect on astrocyte aquaporin. A better understanding of these molecular
mechanisms may lead to the development of novel therapeutics for management of
PTBE with a better side effect profile.
PMID- 27613644
TI - High urinary excretion of kidney injury molecule-1 predicts adverse outcomes in
acute kidney injury: a case control study.
AB - BACKGROUND: Acute kidney injury (AKI) is a common clinical syndrome with poor
prognosis. The insensitivity and non-specificity of traditional markers of renal
dysfunction prevent timely estimation of the severity of renal injury, and the
administration of possible therapeutic agents. Urinary kidney injury molecule-1
(uKIM-1) is a marker of epithelial injury of renal tubules. Different uKIM-1
levels are associated with various degrees of renal injury. This study sought to
evaluate uKIM-1 as a predictor of renal prognosis by analyzing uKIM-1 levels in
patients with AKI. METHODS: A total of 258 patients were screened, 201 patients
were enrolled in the study, and 17 patients were lost to follow up. Therefore,
184 AKI patients were included in this study and were classified into transient
AKI and renal AKI groups according to short-term renal function recovery (48 h).
Changes in renal function were observed for one year during regular follow up,
and risk factors that affected renal prognosis were analyzed. RESULTS: The uKIM-1
level in the renal AKI group was significantly higher than that in the transient
AKI group. The receiver operating characteristic area under the curve (ROC-AUC)
of uKIM-1 for the diagnosis of renal AKI was 0.691, and its sensitivity and
specificity were 66.3 % and 64.7 %, respectively. The uKIM-1 level at AKI
occurrence was significantly higher in the group with deterioration in renal
function than in the group with stable renal function. Thus, uKIM-1 level is a
prognostic factor for poor renal prognosis. ROC curve analysis demonstrated that
the AUC for the prediction of renal function progression on the basis of uKIM-1
levels in patients with renal AKI and AKI was 0.680 and 0.703, respectively; the
sensitivity was 78.6 % and 78.4 %, respectively; and the specificity was 57.9 %
and 60.8 %, respectively. uKIM-1 > 2.37 ng/mg in patients with AKI positively
correlated with poor renal prognosis. CONCLUSIONS: uKIM-1 levels sensitively
predict the renal prognosis of patients with AKI, and they may be used as early
screening indicators for poor renal prognosis.
PMID- 27613647
TI - David Oliver: No more broken promises.
PMID- 27613646
TI - Efficacy of a Social Self-Value Empowerment Intervention to Improve Quality of
Life of HIV Infected People Receiving Antiretroviral Treatment in Nepal: A
Randomized Controlled Trial.
AB - We developed a comprehensive and culturally applicable empowerment intervention
social self-value package with an aim to assess its efficacy in order to improve
the quality of life (QoL) of HIV infected people receiving antiretroviral
treatment. Participants were randomly allocated to receive either six weekly
intervention sessions or standard care. Nonlinear mixed-effects models were
performed to compare changes in empowerment scores over time. Between September
and November 2014, 1447 individuals were screened, of whom 132 were randomly
assigned to either the intervention or control group. The mean scores of
empowerment, social support and quality of life increased and stigma scores were
reduced in the intervention group at 3- and 6-months. An intervention effect on
social support, stigma and QoL was significantly increased by time and group with
low and high empowerment. No adverse events were reported. The empowerment
intervention was efficacious in improving QoL of HIV infected people.
PMID- 27613645
TI - The Role of ARV Associated Adverse Drug Reactions in Influencing Adherence Among
HIV-Infected Individuals: A Systematic Review and Qualitative Meta-Synthesis.
AB - Poor adherence remains a major barrier to achieving the clinical and public
health benefits of antiretroviral drugs (ARVs). A systematic review and
qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions
may influence ARV adherence. Thirty-nine articles were identified, and 33
reported that ARV adverse drug reactions decreased adherence and six studies
found no influence. Visually noticeable adverse drug reactions and psychological
adverse reactions were reported as more likely to cause non-adherence compared to
other adverse drug reactions. Six studies reported a range of adverse reactions
associated with EFV-containing regimens contributing to decreased adherence.
Informing HIV-infected individuals about ARV adverse drug reactions prior to
initiation, counselling about coping mechanisms, and experiencing the
effectiveness of ARVs on wellbeing may improve ARV adherence.
PMID- 27613648
TI - Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in
healthy cats.
AB - INTRODUCTION: To investigate the pharmacokinetics and pharmacodynamics of oral
pimobendan in conscious, healthy cats. ANIMALS: Eight healthy adult cats.
MATERIALS AND METHODS: A randomised, single-blinded, crossover design was used.
Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control
substance (3-mL water) were administered to each cat. Blood collection,
echocardiography, and oscillometric blood pressure measurements were performed
repeatedly for 12 h following each dose. Plasma concentrations of pimobendan and
the active metabolite, O-desmethylpimobendan (ODMP), were quantified using ultra
high-performance liquid chromatography tandem mass spectrometry. Cardiovascular
parameters were evaluated for between- and within-treatment effects over time
using linear mixed modelling. RESULTS: Pimobendan was rapidly absorbed and
converted to ODMP with the pimobendan AUC0-infinity greater than ODMP AUC0
infinity (ODMP:pimobendan AUC0-infinity ratio 0.6 [LD] and 0.5 [HD]) despite a
longer elimination half-life of ODMP (pimobendan t1/2 0.8 h vs. ODMP t1/2 1.6 h
[LD]; pimobendan t1/2 0.7 h vs. ODMP t1/2 1.3 h [HD]). Averaged across all time
points, pimobendan increased several measures of systolic function; however, its
effect could not be further characterised. Although treatment was well-tolerated,
two cats vomited following HD and another had a ventricular premature beat
recorded following LD. CONCLUSIONS: The lower ODMP:pimobendan AUC0-infinity ratio
compared to that observed previously in dogs suggests reduced metabolism in cats.
Treatment effects were observed in measures of systolic function; however, the
duration of action and differences in effects between the two pimobendan doses
could not be characterised. Further studies are required to evaluate pimobendan
in feline cardiovascular medicine.
PMID- 27613649
TI - Anodal stimulation in two dogs with transvenous permanent bipolar pacemakers.
AB - Management of symptomatic bradyarrhythmias such as complete atrioventricular
block often involves permanent implantation of a transvenous pacemaker. Both
during and after implantation, the operator can telemetrically assess and adjust
a variety of electrical parameters associated with the pacemaker function in
order to optimize the sensitivity, reliability, and power consumption of the
device. Herein, we report an unexpected change in the paced electrocardiographic
QRS complex morphology in two dogs undergoing bipolar pacing associated with
changes in the pacemaker output amplitude settings first detected during
threshold testing. The exclusivity of the electrocardiographic changes solely on
pacemaker output settings, consistency between the surface electrocardiogram and
ventricular endocardial electrogram, and resolution of this phenomenon when dogs
were re-programmed to unipolar pacing is consistent with depolarization of the
ventricular myocardium by the anodal electrode of the pacing lead at high
pacemaker amplitudes. Anodal stimulation is a potential cause of varying QRS
complex morphology witnessed during pacemaker evaluation and interrogation.
PMID- 27613651
TI - Multi-sector thermo-physiological head simulator for headgear research.
AB - A novel thermo-physiological human head simulator for headgear testing was
developed by coupling a thermal head manikin with a thermo-physiological model.
As the heat flux at head-site is directly measured by the head manikin, this
method provides a realistic quantification of the heat transfer phenomena
occurring in the headgear, such as moisture absorption-desorption cycles,
condensation, or moisture migration across clothing layers. Before coupling, the
opportunities of the head manikin for representing the human physiology were
evaluated separately. The evaluation revealed reduced precision in forehead and
face temperature predictions under extreme heterogeneous temperature
distributions and no initial limitation for simulating temperature changes
observed in the human physiology. The thermo-physiological model predicted higher
sweat rates when applied for coupled than for pure virtual simulations. After
coupling, the thermo-physiological human head simulator was validated using eight
human experiments. It precisely predicted core, mean skin, and forehead
temperatures with average rmsd values within the average experimental standard
deviation (rmsd of 0.20 +/- 0.15, 0.83 +/- 0.34, and 1.04 +/- 0.54 degrees C,
respectively). However, in case of forehead, precision was lower for the
exposures including activity than for the sedentary exposures. The representation
of the human sweat evaporation could be affected by a reduced evaporation
efficiency and the manikin sweat dynamics. The industry will benefit from this
thermo-physiological human head simulator leading to the development of helmet
designs with enhanced thermal comfort and, therefore, with higher acceptance by
users.
PMID- 27613652
TI - Analytic Modeling of Neural Tissue: I. A Spherical Bidomain.
AB - Presented here is a model of neural tissue in a conductive medium stimulated by
externally injected currents. The tissue is described as a conductively isotropic
bidomain, i.e. comprised of intra and extracellular regions that occupy the same
space, as well as the membrane that divides them, and the injection currents are
described as a pair of source and sink points. The problem is solved in three
spatial dimensions and defined in spherical coordinates [Formula: see text]. The
system of coupled partial differential equations is solved by recasting the
problem to be in terms of the membrane and a monodomain, interpreted as a
weighted average of the intra and extracellular domains. The membrane and
monodomain are defined by the scalar Helmholtz and Laplace equations,
respectively, which are both separable in spherical coordinates. Product
solutions are thus assumed and given through certain transcendental functions.
From these electrical potentials, analytic expressions for current density are
derived and from those fields the magnetic flux density is calculated. Numerical
examples are considered wherein the interstitial conductivity is varied, as well
as the limiting case of the problem simplifying to two dimensions due to
azimuthal independence. Finally, future modeling work is discussed.
PMID- 27613650
TI - An integrated view on the oxygenation responses to incremental exercise at the
brain, the locomotor and respiratory muscles.
AB - In the past two decades oxygenation responses to incremental ramp exercise,
measured non-invasively by means of near-infrared spectroscopy at different
locations in the body, have advanced the insights on the underpinning mechanisms
of the whole-body pulmonary oxygen uptake ([Formula: see text]) response. In
healthy subjects the complex oxygenation responses at the level of locomotor and
respiratory muscles, and brain were simplified and quantified by the detection of
breakpoints as a deviation in the ongoing response pattern as work rate
increases. These breakpoints were located in a narrow intensity range between 75
and 90 % of the maximal [Formula: see text] and were closely related to
traditionally determined thresholds in pulmonary gas exchange (respiratory
compensation point), blood lactate measurements (maximal lactate steady state),
and critical power. Therefore, it has been assumed that these breakpoints in the
oxygenation patterns at different sites in the body might be equivalent and
could, therefore, be used interchangeably. In the present review the typical
oxygenation responses (at locomotor and respiratory muscle level, and cerebral
level) are described and a possible framework is provided showing the
physiological events that might link the breakpoints at different body sites with
the thresholds determined from pulmonary gas exchange and blood lactate
measurements. However, despite a possible physiological association, several
arguments prevent the current practical application of these breakpoints measured
at a single site as markers of exercise intensity making it highly questionable
whether measurements of the oxygenation response at one single site can be used
as a reflection of whole-body responses to different exercise intensities.
PMID- 27613654
TI - Biomarkers of Airway Type-2 Inflammation and Integrating Complex Phenotypes to
Endotypes in Asthma.
AB - PURPOSE OF REVIEW: Over the past decade, the most important advance in the field
of asthma has been the widespread recognition that asthma is a heterogeneous
disease driven by multiple molecular processes. RECENT FINDINGS: The most well
established molecular mechanism in asthma is increased airway type-2
inflammation, and consequently, non-invasive biomarkers of increased airway type
2 inflammation, such as blood eosinophil counts or blood periostin levels, have
proven important in stratifying asthma patients in clinical trials of type-2
cytokine inhibitors. However, it remains ambiguous how well these non-invasive
biomarkers represent airway measures of type-2 inflammation in asthma. As a
result, the utility of these biomarkers to assist with asthma management or as
research tools to better understand asthma pathogenesis remains unclear. This
article reviews primary data assessing biomarkers of airway type-2 inflammation
in asthma and describes how the use of biomarkers can advance a precision
medicine approach to asthma treatment.
PMID- 27613656
TI - Proactive epigenesis and ethical innovation: A neuronal hypothesis for the
genesis of ethical rules.
PMID- 27613655
TI - Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized
Children.
AB - Acute otitis media is a common infection in children. Most acute otitis media
episodes can be treated at an outpatient setting with antimicrobials, or only
expectant observation. Hospital treatment with parenteral medication, and
myringotomy or tympanostomy, may be needed to treat those with severe, prolonged
symptoms, or with complications. The most common intratemporal complication of
acute otitis media is acute mastoiditis. If a child with acute mastoiditis does
not respond to this treatment, or if complications develop, further examinations
and other surgical procedures, including mastoidectomy, are considered. Since the
treatment of complicated acute otitis media and complicated acute mastoiditis
differs, it is important to differentiate these two conditions. This article
focuses on the differential diagnostics of acute otitis media and acute
mastoiditis in children.
PMID- 27613653
TI - Novel Biologicals for the Treatment of Allergic Diseases and Asthma.
AB - PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed
during the last few years, and major advances were reported for the treatment of
allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food
allergy, and asthma. Here, we review biologicals targeting the type 2 immune
response involving Th2 cells, type 2 innate lymphoid cells, natural killer T
cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL
31, tumor necrosis factor alpha (TNF-alpha), and thymic stromal lymphopoietin
(TSLP). RECENT FINDINGS: The biologicals that have been currently approved for
asthma are omalizumab targeting IgE and reslizumab and mepolizumab targeting
interleukin (IL)-5. Many other monoclonal antibodies are currently in various
phases of clinical development. The new biological therapies for allergic
diseases will eventually be tailored to the endotypes of these diseases and the
identification of novel biomarkers. Further development of novel biologicals for
the treatment of allergic diseases and asthma will be possible upon improved
understanding of mechanisms of allergic diseases. Accordingly, further refinement
of endotypes of allergen-specific and non-specific type 2 immune response and
related inflammatory mediators is needed for optimal treatment of allergic
diseases.
PMID- 27613657
TI - Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single
center experience.
AB - BACKGROUND: Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on
their management is limited. We here investigated the clinicopathological
characteristics, surgical and survival outcomes in G-NENs among Chinese.
Moreover, we will discuss their prognostic value. METHODS: From existing
databases of the West China Hospital, we retrospectively identified 135
consecutive patients who were surgically treated and pathologically diagnosed as
G-NENs from January 2009 to August 2015. RESULTS: This entire cohort comprised 98
males and 37 females, with a median age of 60 years. Twenty-five patients
underwent endoscopic resection, while 110 patients underwent open/laparoscopic
surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven
patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine
carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma
(MANEC). The median survival was not achieved for both NET G1 and NET G2 versus
19 months (range 3-48) for NEC G3 and 10.5 months (range 3-45) for MANEC. The 3
year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and
11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical
margin and the newly updated World Health Organization (WHO) classification were
independent predictors of overall survival (OS). CONCLUSIONS: G-NENs are a kind
of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis
even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria
are closely associated with OS for G-NENs.
PMID- 27613658
TI - An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes.
AB - BACKGROUND: Bolus calculators help patients with type 1 diabetes to mitigate the
effect of meals on their blood glucose by administering a large amount of insulin
at mealtime. Intraindividual changes in patients physiology and nonlinearity in
insulin-glucose dynamics pose a challenge to the accuracy of such calculators.
METHOD: We propose a method based on a continuous-discrete unscented Kalman
filter to continuously track the postprandial glucose dynamics and the insulin
sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate
noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is
determined by calculating the steady state of the model and is adjusted once a
day before breakfast. The bolus size is determined by optimizing the postprandial
glucose values based on an estimate of the insulin sensitivity and states, as
well as the announced meal size. Following meal announcements, the meal
compartment and the meal time constant are estimated, otherwise insulin
sensitivity is estimated. RESULTS: We compare the performance of a conventional
linear bolus calculator with the proposed bolus calculator. The proposed basal
bolus calculator significantly improves the time spent in glucose target ( P <
.01) compared to the conventional bolus calculator. CONCLUSION: An adaptive
nonlinear basal-bolus calculator can efficiently compensate for physiological
changes. Further clinical studies will be needed to validate the results.
PMID- 27613659
TI - Reductions in the United Kingdom's Government Housing Benefit and Symptoms of
Depression in Low-Income Households.
AB - Housing security is an important determinant of mental ill health. We used a
quasinatural experiment to evaluate this association, comparing the prevalence of
mental ill health in the United Kingdom before and after the government's April
2011 reduction in financial support for low-income persons who rent private
sector housing (mean reduction of approximately L1,220 ($2,315) per year). Data
came from the United Kingdom's Annual Population Survey, a repeated quarterly
cross-sectional survey. We focused our analysis on renters in the private sector,
disaggregating data between an intervention group receiving the government's
Housing Benefit (n = 36,859) and a control group not receiving the Housing
Benefit (n = 142,205). The main outcome was a binary measure of self-reported
mental health problems. After controlling for preexisting time trends, we
observed that between April 2011 and March 2013, the prevalence of depressive
symptoms among private renters receiving the Housing Benefit increased by 1.8
percentage points (95% confidence interval: 1.0, 2.7) compared with those not
receiving the Housing Benefit. Our models estimated that approximately 26,000
(95% confidence interval: 14,000, 38,000) people newly experienced depressive
symptoms in association with the cuts to the Housing Benefit. We conclude that
reducing housing support to low-income persons in the private rental sector
increased the prevalence of depressive symptoms in the United Kingdom.
PMID- 27613660
TI - Reeves et al. Respond to "Harnessing Housing Natural Experiments".
PMID- 27613661
TI - Invited Commentary: Harnessing Housing Natural Experiments Is Important, but
Beware Differential Misclassification of Difference in Difference.
AB - In this issue of the Journal, Reeves et al. (Am J Epidemiol. 2016;184(6):421-429)
present the findings of a natural experiment analyzing the association between
reduced housing affordability and mental ill health. Their difference-in
difference analysis of cross-sectional, quarterly population health surveys
administered before and after implementation of a policy to reduce Housing
Benefit payments in the United Kingdom in April 2011 represents an important way
to assess the impact of a national housing policy shift on public health. It is a
well-conducted study harnessing a natural experiment and adds to the weight of
evidence supporting an association between housing costs and mental health.
However, quantitative bias analysis based on the reported findings suggests that
a small amount of differential (by unblinded Housing Benefit status)
misclassification bias in the outcome may be enough to explain the observed
association. Our analysis of possible misclassification bias in the outcome used
in the study highlights the need for caution when a difference-in-difference
estimate is small, the population is not blinded to its postintervention exposure
status, and the outcome measure is subjective and prone to differential (by
unblinded exposure or treatment status) misclassification.
PMID- 27613662
TI - Deformable image registration between pathological images and MR image via an
optical macro image.
AB - Computed tomography (CT) and magnetic resonance (MR) imaging have been widely
used for visualizing the inside of the human body. However, in many cases,
pathological diagnosis is conducted through a biopsy or resection of an organ to
evaluate the condition of tissues as definitive diagnosis. To provide more
advanced information onto CT or MR image, it is necessary to reveal the
relationship between tissue information and image signals. We propose a
registration scheme for a set of PT images of divided specimens and a 3D-MR image
by reference to an optical macro image (OM image) captured by an optical camera.
We conducted a fundamental study using a resected human brain after the death of
a brain cancer patient. We constructed two kinds of registration processes using
the OM image as the base for both registrations to make conversion parameters
between the PT and MR images. The aligned PT images had shapes similar to the OM
image. On the other hand, the extracted cross-sectional MR image was similar to
the OM image. From these resultant conversion parameters, the corresponding
region on the PT image could be searched and displayed when an arbitrary pixel on
the MR image was selected. The relationship between the PT and MR images of the
whole brain can be analyzed using the proposed method. We confirmed that same
regions between the PT and MR images could be searched and displayed using
resultant information obtained by the proposed method. In terms of the accuracy
of proposed method, the TREs were 0.56+/-0.39mm and 0.87+/-0.42mm. We can analyze
the relationship between tissue information and MR signals using the proposed
method.
PMID- 27613663
TI - Update of syncytiotrophoblast derived extracellular vesicles in normal pregnancy
and preeclampsia.
AB - The release of extracellular vesicles (EV) by the syncytiotrophoblast (STB) may
be an important mechanism by which the placenta signals to the mother. STB
derived EV (STBEV) are comprised predominantly of exosomes (50-150nm) and
microvesicles (100-1000nm) that contain bioactive mediators such as proteins,
nucleic acids and lipids. They, along with larger syncytial nuclear aggregates
are released by the STB into the maternal circulation throughout gestation in
normal pregnancy where they appear to have an immunoregulatory role, inhibiting T
cell and NK cell responses. In pre-eclampsia (PE) STBEV are released in
significantly increased numbers and have pro-inflammatory, anti-angiogenic and
procoagulant activity, implicating them in the maternal systemic inflammation,
endothelial dysfunction and activation of the clotting system which typifies the
disorder. Research has focused on understanding the biological significance of
STBEV by measuring their size and repertoire of molecules carried and how they
differ in normal pregnancy and PE, using techniques such as Nanoparticle Tracking
Analysis, flow cytometry and mass spectrometry. We have also found alterations in
STBEV surface glycans associated with PE. The goal is to better understand the
role STBEV play in normal pregnancy and PE and whether they are potential
biomarkers of placental pathology and therapeutic targets in PE.
PMID- 27613664
TI - Exercise reverses age-related vulnerability of the retina to injury by preventing
complement-mediated synapse elimination via a BDNF-dependent pathway.
AB - Retinal ganglion cells (RGCs) become increasingly vulnerable to injury with
advancing age. We recently showed that this vulnerability can be strongly
modified in mice by exercise. However, the characteristics and underlying
mechanisms of retinal protection with exercise remain unknown. Hence, the aim of
this study was to investigate cellular changes associated with exercise-induced
protection of aging retinal cells and the role of local and peripheral trophic
signalling in mediating these effects. We focussed on two molecules that are
thought to play key roles in mediating beneficial effects of exercise: brain
derived neurotrophic factor (BDNF) and AMP-activated protein kinase (AMPK). In
middle-aged (12 months old) C57BL/6J mice, we found that exercise protected RGCs
against dysfunction and cell loss after an acute injury induced by elevation of
intra-ocular pressure. This was associated with preservation of inner retinal
synapses and reduced synaptic complement deposition. Retinal expression of BDNF
was not upregulated in response to exercise alone. Rather, exercise maintained
BDNF levels in the retina, which were decreased postinjury in nonexercised
animals. Confirming a critical role for BDNF, we found that blocking BDNF
signalling during exercise by pharmacological means or genetic knock-down
suppressed the functional protection of RGCs afforded by exercise. Protection of
RGCs with exercise was independent of activation of AMPK in either retina or
skeletal muscle. Our data support a previously unidentified mechanism in which
exercise prevents loss of BDNF in the retina after injury and preserves neuronal
function and survival by preventing complement-mediated elimination of synapses.
PMID- 27613665
TI - HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first
trimester trophoblast cells.
AB - PROBLEM: Zika virus (ZIKV) has gained public concern for its association with
microcephaly in infants born to ZIKV-infected mothers. To reach the fetus the
virus must overcome the defense mechanisms provided by trophoblast cells.
Additionally, in the first trimester, the integrity of the placenta is critical
for fetal protection as damage to differentiating trophoblast can affect
placental formation and function. We sought to investigate the effect of ZIKV
infection on trophoblast cells and the factors that might increase the risk for
ZIKV infection during pregnancy. METHODS: First-trimester human trophoblast
cells, Swan 7.1, were infected with ZIKV, herpes simplex virus-2 (HSV-2), and
yellow fiver (YFV). C57BL/6 pregnant mice were infected with HSV-2, ZIKV, or
coinfection. Placental viral titers were determined by RT-PCR. RESULTS: ZIKV
infection induces apoptosis in first-trimester trophoblasts and prevents
differentiation of these cells. Furthermore, HSV-2 infection enhances placental
sensitivity to ZIKV by enhancing the expression of TAM receptors, which
facilitate ZIKV cell entry. CONCLUSION: These findings may explain the mechanism
by which ZIKV breaches the placental barrier to access the fetus. Furthermore,
our results suggest that patients with HSV-2 infection are at a higher risk for
the teratogenic effects induced by ZIKV.
PMID- 27613666
TI - Cysts of the canal of Nuck: A rare sonographic diagnosis.
AB - The canal of Nuck is a remnant of a peritoneal evagination associated with the
round ligament in women. Rarely, the canal of Nuck can remain patent allowing for
development of cysts. These cysts are difficult to diagnose due to their rare
incidence and because they are often mistaken for other causes of inguinal pain
in women. This case series of three women presenting with groin or labial masses
highlights the role of sonography as the primary imaging modality in the
diagnosis of canal of Nuck cysts. (c) 2016 Wiley Periodicals, Inc. J Clin
Ultrasound 45:175-178, 2017.
PMID- 27613668
TI - Fluorescence peak integration ratio IC:IT as a new potential indicator tracing
the compositional changes in chromophoric dissolved organic matter.
AB - The present study demonstrates that the ratio of fluorescence integration of peak
C to peak T (IC:IT) can be used as an indicator tracing the compositional
dynamics of chromophoric dissolved organic matter (CDOM). CDOM absorption and
fluorescence spectroscopy and stable isotope delta13C were determined on a
seasonal basis in seventeen Chinese inland waters as well as in a series of
mixing and photodegradation experiments in the lab. A strong positive linear
correlation was recorded between IC:IT and the ratio of terrestrial humic-like C1
to tryptophan-like C4 (C1:C4) derived by parallel factor analysis. The r2 for the
linear fitting between IC:IT and C1:C4 (r2=0.80) was notably higher than between
C1:C4 and other indices tested, including the ratio of CDOM absorption at 250nm
to 365nm, i.e. a(250):a(365) (r2=0.09), spectral slope (S275-295) (r2=0.26),
spectral slope ratio (SR) (r2=0.31), the humification index (HIX) (r2=0.47), the
recent autochthonous biological contribution index (BIX) (r2=0.27), and a
fluorescence index (FI370) (r2=0.07). IC:IT exhibited larger variability than the
remaining six indices and a closer correlation with stable isotope delta13C than
that observed for a(250):a(365), S275-295, SR, FI370, and BIX during field
campaigns. Confirming our field observations, significant correlations were
recorded between IC:IT and the remaining six indices, and IC:IT also demonstrated
notably larger variability than the six other indices during our wastewater
addition experiment. Compared with HIX, eutrophic water addition and
photobleaching substantially decreased IC:IT but had no pronounced effect on
a(250):a(365), S275-297, SR, FI370, and BIX, further suggesting that IC:IT is the
most efficient indicator of the CDOM compositional dynamics.
PMID- 27613667
TI - Dopamine and temporal attention: An attentional blink study in Parkinson's
disease patients on and off medication.
AB - The current study aimed to shed more light on the role of dopamine in temporal
attention. To this end, we pharmacologically manipulated dopamine levels in a
large sample of Parkinson's disease patients (n=63) while they performed an
attentional blink (AB) task in which they had to identify two targets (T1 and T2)
presented in close temporal proximity among distractors. We specifically examined
1) differences in the magnitude of the AB between unmedicated Parkinson patients,
who have depleted levels of striatal dopamine, and healthy controls, and 2)
effects of two dopaminergic medications (l-DOPA and dopamine agonists) on the AB
in the Parkinson patients at the group level and as a function of individual
baseline performance. In line with the notion that relatively low levels of
striatal dopamine may impair target detection in general, Parkinson patients OFF
medications displayed overall poor target perception compared to healthy
controls. Moreover, as predicted, effects of dopaminergic medication on AB
performance critically depended on individual baseline AB size, although this
effect was only observed for l-DOPA. l-DOPA generally decreased the size of the
AB in patients with a large baseline AB (i.e., OFF medications), while l-DOPA
generally increased the AB in patients with a small baseline AB. These findings
may support a role for dopamine in the AB and temporal attention, more generally
and corroborate the notion that there is an optimum dopamine level for cognitive
function. They also emphasize the need for more studies that examine the separate
effects of DA agonists and l-DOPA on cognitive functioning.
PMID- 27613669
TI - Factors affecting the formation of nitrogenous disinfection by-products during
chlorination of aspartic acid in drinking water.
AB - The formation of emerging nitrogenous disinfection by-products (N-DBPs) from the
chlorination of aspartic acid (Asp) was investigated. The yield of
dichloroacetonitrile (DCAN) was higher than other N-DBPs, such as
dichloroacetamide(DCAcAm) and chloropicrin (TCNM) during the chlorination of Asp.
The formation of DCAN, DCAcAm, and TCNM all showed a trend of first increasing
and then decreasing during the chlorination of Asp with increasing contact time.
The dosage of chlorine had an impact on the formation of DCAN, DCAcAm, and TCNM.
The highest yields of DCAN and DCAcAm appeared when the Cl2/Asp molar ratio was
about 20, the yield of TCNM increased with increasing the Cl2/Asp molar ratio
from 5 to 30 and TCNM was not produced when the ratio was less than 5. Cyanogen
chloride (CNCl) was detected when the Cl2/Asp molar ratio was lower than 5. N
DBPs formation was influenced by pH. DCAN formation increased with increasing pH
from 5 to 6 and then decreased with increasing pH from 6 to 9, but DCAcAm and
TCNM increased with increasing pH from 5 to 8 and then decreased. Higher
temperatures reduced the formation of DCAN and DCAcAm, but increased TCNM
formation. DCAN and DCAcAm formation decreased, and relatively stable TCNM
formation increased, with increasing free chlorine contact time during
chloramination. N-nitrosodimethylamine (NDMA) was produced during chloramination
of Asp and increased with prolonged chloramination contact time. The presence of
bromide ions enhanced the yields of haloacetonitriles and shifted N-DBPs to more
brominated species.
PMID- 27613670
TI - Estimating years of life lost from cardiovascular mortality related to air
pollution in Guangzhou, China.
AB - Previous studies have mainly used mortality or morbidity as the health outcome to
examine the air pollution-health association. Little evidence is available on
relationships between air pollutants and years of life lost (YLL). We aimed to
estimate the YLL from cardiovascular mortality due to air pollution. Daily data
on weather and air pollutants and individual data of all registered deaths for
years 2004-2007 were obtained in Guangzhou, China. The generalized additive model
was used to assess the YLL associated with 10MUg/m3 increases in NO2, SO2 and
PM10. We found that the mean daily YLL was 248, 87.5 and 73.7 for deaths from
cardiovascular disease (CVD), stroke and ischemic heart disease (IHD),
respectively. A significant linear correlation was observed between air pollution
and YLL due to cardiovascular disease. The effects of air pollutants on YLL were
immediate and lasted for two days. A 10MUg/m3 increase above the corresponding
threshold of 55.6MUg/m3, 40.4MUg/m3 and 0MUg/m3 in NO2, PM10 and SO2 was related
to YLL increase of 1.8 (95% CI: 0.8-2.9), 2.8 (1.7-3.8) and 2.6 (1.2-4.0) years
at lag 0-1days for CVD, respectively. The estimates of YLL associated with NO2
and PM10 were higher in men than women. The air pollutants-related YLL was higher
among young people and those with low education level, compared to the elderly
and those with high education level, respectively. These findings confirmed YLL
provides a complementary strategy for assessing the health effect of air
pollution. This study underscores the necessity of the reduction of air pollution
benefiting public health.
PMID- 27613671
TI - Base cations and micronutrients in soil aggregates as affected by enhanced
nitrogen and water inputs in a semi-arid steppe grassland.
AB - The intensification of grassland management by nitrogen (N) fertilization and
irrigation may threaten the future integrity of fragile semi-arid steppe
ecosystems by affecting the concentrations of base cation and micronutrient in
soils. We extracted base cations of exchangeable calcium (Ca), magnesium (Mg),
potassium (K), and sodium (Na) and extractable micronutrients of iron (Fe),
manganese (Mn), copper (Cu), and zinc (Zn) from three soil aggregate sizes
classes (microaggregates, <0.25mm; small macroaggregates, 0.25-2mm; large
macroaggregates, >2mm) from a 9-yearN and water field manipulation study. There
were significantly more base cations (but not micronutrients) in microaggregates
compared to macroaggregates which was related to greater soil organic matter and
clay contents. Nitrogen addition significantly decreased exchangeable Ca by up to
33% in large and small macroaggregates and exchangeable Mg by up to 27% in three
aggregates but significantly increased extractable Fe, Mn and Cu concentrations
(by up to 262%, 150%, and 55%, respectively) in all aggregate size classes.
However, water addition only increased exchangeable Na, while available Fe and Mn
were decreased by water addition when averaging across all N treatments and
aggregate classes. The loss of exchangeable Ca and Mg under N addition and
extractable Fe and Mn in soil aggregates under water addition might potentially
constrain the productivity of this semi-arid grassland ecosystem.
PMID- 27613672
TI - The microbial degradation of 2,4,6-tribromophenol (TBP) in water/sediments
interface: Investigating bioaugmentation using Bacillus sp. GZT.
AB - The substance 2,4,6-Tribromophenol (TBP) is used as a flame retardant in
electronic and electric devices, and is a replacement for pentachlorophenol in
wood preservation. TBP is a contaminant in different environmental matrices, at
levels where treatment is required. This study examined the relationship between
the bioaugmention of TBP degradation and the evolution of the microbial community
in river water/sediment microcosms. When compared with unamended controls,
bioaugmentation with Bacillus sp. GZT effectively enhanced TBP biodegradation,
with approximately 40.7% of the TBP removal after a 7-week incubation period,
without a lag phase (p<0.01). Amendments with 2-bromophenol, 2,6-dibromophenol,
and 2,4-dibromophenol did not promote TBP biodegradation in river water/sediments
(p>0.05). However, TBP biodegradation was enhanced by adding other additives,
including NaCl, humic acid, sodium lactate, and sodium propionate alone,
especially glucose and yeast extract. A metagenomics analysis of the total 16S
rRNA genes from the treatment system with bioaugmentation showed that four
microbial phyla were dominant: Proteobacteria (52.08-66.22%), Actinobacteria
(20.03-5.47%), Bacteroidetes (6.68-13.68%), and Firmicutes (4.53-20.83%). This
study highlights the possible benefits using bioaugmentation with GZT to
remediate TBP-polluted water and sediments.
PMID- 27613673
TI - Assessment of nitrogen and phosphorus flows in agricultural and urban systems in
a small island under limited data availability.
AB - Nitrogen (N) and phosphorus (P) are two essential macronutrients required in
agricultural production. The major share of this production relies on chemical
fertilizer that requires energy and relies on limited resources (P). Since these
nutrients are lost to the environment, there is a need to shift from this linear
urban metabolism to a circular metabolism in which N and P from domestic waste
and wastewater are reused in agriculture. A first step to facilitate a transition
to more circular urban N and P management is to understand the flows of these
resources in a coupled urban-agricultural system. For the first time this paper
presents a Substance Flow Analysis (SFA) approach for the assessment of the
coupled agricultural and urban systems under limited data availability in a small
island. The developed SFA approach is used to identify intervention points that
can provide N and P stocks for agricultural production. The island of St.
Eustatius, a small island in the Caribbean, was used as a case study. The model
developed in this study consists of eight sub-systems: agricultural and natural
lands, urban lands, crop production, animal production, market, household
consumption, soakage pit and open-dump landfill. A total of 26 flows were
identified and quantified for a period of one year (2013). The results showed
that the agricultural system is a significant source for N and P loss because of
erosion/run-off and leaching. Moreover, urban sanitation systems contribute to
deterioration of the island's ecosystem through N and P losses from domestic
waste and wastewater by leaching and atmospheric emission. Proposed interventions
are the treatment of blackwater and greywater for the recovery of N and P. In
conclusion, this study allows for identification of potential N and P losses and
proposes mitigation measures to improve nutrient management in a small island
context.
PMID- 27613674
TI - Seasonal and diurnal variations of BTEX compounds in the semi-urban environment
of Orleans, France.
AB - Atmospheric concentrations of BTEX (benzene, toluene, ethylbenzene and xylene)
were measured at a semi-urban site in Orleans, France, from October 2010 to
August 2011. Air samples were collected by multi-bed adsorbent tubes. The BTEX
concentrations were determined by thermal desorption-gas chromatography-mass
spectrometry detector (TD-GC-MSD) technique. The average concentrations of the
total measured BTEX during spring, summer, autumn and winter were 724.2, 337.4,
682.3, 823.0ppt, respectively. Maximal values for their diurnal variations
usually happened during rush hours in the morning and late afternoon, and the
minimal values in the daytime usually happened in around noontime. The diurnal
variation of BTEX in four seasons and the correlations between BTEX and NO
indicated that vehicular exhaust might be the primary source of BTEX. Benzene was
found in relatively high levels and the B/T ratio was significant high in spring,
indicating an irregular emission source of benzene other than traffic-related
emissions.
PMID- 27613675
TI - Source apportionment of PM2.5 at urban and suburban areas of the Pearl River
Delta region, south China - With emphasis on ship emissions.
AB - Daily PM2.5 samples were collected at an urban site in Guangzhou in 2014 and at a
suburban site in Zhuhai in 2014-2015. Samples were subject to chemical analysis
for various chemical components including organic carbon (OC), element carbon
(EC), major water-soluble inorganic ions, and trace elements. The annual average
PM2.5 mass concentration was 48+/-22MUgm-3and 45+/-25MUgm-3 in Guangzhou and
Zhuhai, respectively, with the highest seasonal average concentration in winter
and the lowest in summer at both sites. Regional transport of pollutants
accompanied with different air mass origins arriving at the two sites and
pollution sources in between the two cities caused larger seasonal variations in
Zhuhai (>a factor of 3.5) than in Guangzhou (17% of PM2.5 mass concentrations.
PMID- 27613676
TI - Bioaccumulation of silver in Daphnia magna: Waterborne and dietary exposure to
nanoparticles and dissolved silver.
AB - Silver nanoparticles (Ag-NP) are incorporated into commercial products as
antimicrobial agents, which potentiate their emission to the environment. The
toxicity of Ag-NP has been associated with the release of Ag ions (Ag+), which
are more toxic to aquatic organisms than Ag-NP. In this study, a toxicokinetics
approach was applied to compare the potential of Daphnia magna to accumulate Ag
from either Ag-NP or AgNO3 through different exposure routes: a) water, b) diet
and c) water and diet. A one-compartment kinetics model was applied to describe
the development of Ag body concentrations over time and derive uptake (k1w; k1d)
and elimination (k2) rate constants. Under water-only exposure, AgNO3 induced
higher Ag uptake rate constants and bioconcentration factors when compared to Ag
NP. For dietary exposure, no differences in Ag concentrations in D. magna, along
with the kinetics parameters, were found for both Ag forms. Simultaneous water
and dietary exposures to Ag-NP induced higher Ag concentrations in D. magna
compared to AgNO3. In this combined exposure, uptake from water explains most for
the increase in Ag body concentration in D. magna for Ag-NP exposure, whereas
uptake from the diet was the major contributor for the increase in Ag
concentration in D. magna under AgNO3 exposure. Biomagnification was not observed
for any of the exposure routes applied in this study, neither for Ag-NP nor for
AgNO3.
PMID- 27613677
TI - Clinical and neurophysiological features of familial cortical myoclonic tremor
with epilepsy.
AB - OBJECTIVE: Familial cortical myoclonic tremor with epilepsy is a rare epilepsy
syndrome. Herein, we report on nine Chinese familial cortical myoclonic tremor
with epilepsy pedigrees to delineate its clinical and neurophysiological
features. METHODS: Detailed clinical and neurophysiological data were obtained.
Somatosensory evoked potential amplitudes and clinical profile were analyzed
using multilevel statistical models. Age-at-onset anticipation was analyzed using
Kaplan-Meier survival analysis. RESULTS: Fifty-five patients were interviewed
directly, whose mean age at onset of cortical tremor and generalized tonic-clonic
seizures were 31.0 +/- 8.3 and 36.0 +/- 7.9 years. Giant somatosensory evoked
potential was detected in 87.5% (28 of 32) of patients, and long-latency cortical
reflex was detected in 93.5% (29 of 31). Cortical tremor severity was
significantly higher in patients with longer disease duration of cortical tremor
(P = 0.0061). Somatosensory evoked potential amplitudes were significant higher
in patients with higher level of cortical tremor severity (P = 0.0003) and those
using antiepileptic drugs (P = 0.0150). Age-at-onset anticipation of cortical
tremor with paternal transmission was found with statistical significance (P =
0.022). CONCLUSION: We provided the clinical and neurophysiological features of
familial cortical myoclonic tremor with epilepsy patients. This study is reported
for the presentation of this rare disease in a Chinese population with the
largest single report on familial cortical myoclonic tremor with epilepsy
worldwide. Age-at-onset anticipation of cortical tremor with paternal
transmission was statistically significant, which further confirmed a possibility
of unstable expanding repeat in the genetic mechanism of familial cortical
myoclonic tremor with epilepsy. (c) 2016 International Parkinson and Movement
Disorder Society.
PMID- 27613678
TI - The Escherichia coli rhaSR-PrhaBAD Inducible Promoter System Allows Tightly
Controlled Gene Expression over a Wide Range in Pseudomonas aeruginosa.
AB - The araC-ParaBAD inducible promoter system is tightly controlled and allows gene
expression to be modulated over a wide range in Escherichia coli, which has led
to its widespread use in other bacteria. Although anecdotal evidence suggests
that araC-ParaBAD is leaky in Pseudomonas aeruginosa, neither a thorough analysis
of this inducible promoter system in P. aeruginosa nor a concerted effort to
identify alternatives with improved functionality has been reported. Here, we
evaluated the functionality of the araC-ParaBAD system in P. aeruginosa Using
transcriptional fusions to a lacZ reporter gene, we determined that the
noninduced expression from araC-ParaBAD is high and cannot be reduced by carbon
catabolite repression as it can in E. coli Modulating translational initiation by
altering ribosome-binding site strength reduced the noninduced activity but also
decreased the maximal induced activity and narrowed the induction range.
Integrating the inducible promoter system into the posttranscriptional regulatory
network that controls catabolite repression in P. aeruginosa significantly
decreased the noninduced activity and increased the induction range. In addition
to these improvements in the functionality of the araC-ParaBAD system, we found
that the lacIq-Ptac and rhaSR-PrhaBAD inducible promoter systems had
significantly lower noninduced expression and were inducible over a broader range
than araC-ParaBAD We demonstrated that noninduced expression from the araC
ParaBAD system supported the function of genes involved in antibiotic resistance
and tryptophan biosynthesis in P. aeruginosa, problems that were avoided with
rhaSR-PrhaBAD. rhaSR-PrhaBAD is tightly controlled, allows gene expression over a
wide range, and represents a significant improvement over araC-ParaBAD in P.
aeruginosa IMPORTANCE: We report the shortcomings of the commonly used
Escherichia coli araC-ParaBAD inducible promoter system in Pseudomonas
aeruginosa, successfully reengineered it to improve its functionality, and show
that the E. coli rhaSR-PrhaBAD system is tightly controlled and allows inducible
gene expression over a wide range in P. aeruginosa.
PMID- 27613679
TI - The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human
Microbiomes.
AB - : Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly
mobile and have been ranked as principal risk resistance determinants. However,
the transfer network of the mobile resistome and the forces driving mobile ARG
transfer are largely unknown. Here, we present the whole profile of the mobile
resistome in 23,425 bacterial genomes and explore the effects of phylogeny and
ecology on the recent transfer (>=99% nucleotide identity) of mobile ARGs. We
found that mobile ARGs are mainly present in four bacterial phyla and are
significantly enriched in Proteobacteria The recent mobile ARG transfer network,
which comprises 703 bacterial species and 16,859 species pairs, is shaped by the
bacterial phylogeny, while an ecological barrier also exists, especially when
interrogating bacteria colonizing different human body sites. Phylogeny is still
a driving force for the transfer of mobile ARGs between farm animals and the
human gut, and, interestingly, the mobile ARGs that are shared between the human
and animal gut microbiomes are also harbored by diverse human pathogens. Taking
these results together, we suggest that phylogeny and ecology are complementary
in shaping the bacterial mobile resistome and exert synergistic effects on the
development of antibiotic resistance in human pathogens. IMPORTANCE: The
development of antibiotic resistance threatens our modern medical achievements.
The dissemination of antibiotic resistance can be largely attributed to the
transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the
transfer network of these genes in bacteria and the forces driving the gene flow
is of great importance for controlling and predicting the emergence of antibiotic
resistance in the clinic. Here, by analyzing tens of thousands of bacterial
genomes and millions of human and animal gut bacterial genes, we reveal that the
transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under
ecological constraints. We also found that dozens of ARGs are transferred between
the human and animal gut and human pathogens. This work demonstrates the whole
profile of mobile ARGs and their transfer network in bacteria and provides
further insight into the evolution and spread of antibiotic resistance in nature.
PMID- 27613680
TI - Multiplication of Legionella pneumophila Sequence Types 1, 47, and 62 in Buffered
Yeast Extract Broth and Biofilms Exposed to Flowing Tap Water at Temperatures of
38 degrees C to 42 degrees C.
AB - : Legionella pneumophila proliferates in freshwater environments at temperatures
ranging from 25 to 45 degrees C. To investigate the preference of different
sequence types (ST) for a specific temperature range, growth of L. pneumophila
serogroup 1 (SG1) ST1 (environmental strains), ST47, and ST62 (disease-associated
strains) was measured in buffered yeast extract broth (BYEB) and biofilms grown
on plasticized polyvinyl chloride in flowing heated drinking water originating
from a groundwater supply. The optimum growth temperatures in BYEB were
approximately 37 degrees C (ST1), 39 degrees C (ST47), and 41 degrees C (ST62),
with maximum growth temperatures of 42 degrees C (ST1) and 43 degrees C (ST47 and
ST62). In the biofilm at 38 degrees C, the ST47 and ST62 strains multiplied
equally well compared to growth of the environmental ST1 strain and an indigenous
L. pneumophila non-SG1 strain, all attaining a concentration of approximately 107
CFU/cm-2 Raising the temperature to 41 degrees C did not impact these levels
within 4 weeks, but the colony counts of all strains tested declined (at a
specific decline rate of 0.14 to 0.41 day-1) when the temperature was raised to
42 degrees C. At this temperature, the concentration of Vermamoeba vermiformis in
the biofilm, determined with quantitative PCR (qPCR), was about 2 log units lower
than the concentration at 38 degrees C. In columns operated at a constant
temperature, ranging from 38 to 41 degrees C, none of the tested strains
multiplied in the biofilm at 41 degrees C, in which also V. vermiformis was not
detected. These observations suggest that strains of ST47 and ST62 did not
multiply in the biofilm at a temperature of >=41 degrees C because of the absence
of a thermotolerant host. IMPORTANCE: Growth of Legionella pneumophila in tap
water installations is a serious public health concern. The organism includes
more than 2,100 varieties (sequence types). More than 50% of the reported cases
of Legionnaires' disease are caused by a few sequence types which are very rarely
detected in the environment. Strains of selected virulent sequence types
proliferated in biofilms on surfaces exposed to warm (38 degrees C) tap water to
the same level as environmental varieties and multiplied well as pure culture in
a nutrient-rich medium at temperatures of 42 and 43 degrees C. However, these
organisms did not grow in the biofilms at temperatures of >=41 degrees C. Typical
host amoebae also did not multiply at these temperatures. Apparently,
proliferation of thermotolerant host amoebae is needed to enable multiplication
of the virulent L. pneumophila strains in the environment at elevated
temperatures. The detection of these amoebae in water installations therefore is
a scientific challenge with practical implications.
PMID- 27613681
TI - Aerosol and Surface Deposition Characteristics of Two Surrogates for Bacillus
anthracis Spores.
AB - Spores of an acrystalliferous derivative of Bacillus thuringiensis subsp.
kurstaki, termed Btcry-, are morphologically, aerodynamically, and structurally
indistinguishable from Bacillus anthracis spores. Btcry- spores were dispersed in
a large, open-ended barn together with spores of Bacillus atrophaeus subsp.
globigii, a historically used surrogate for Bacillus anthracis Spore suspensions
(2 * 1012 CFU each of B. atrophaeus subsp. globigii and Btcry-) were aerosolized
in each of five spray events using a backpack misting device incorporating an air
blower; a wind of 4.9 to 7.6 m s-1 was also flowing through the barn in the same
direction. Filter air samplers were situated throughout the barn to assess the
aerosol density of the spores during each release. Trays filled with a surfactant
in aqueous buffer were placed on the floor near the filter samplers to assess
spore deposition. Spores were also recovered from arrays of solid surfaces
(concrete, aluminum, and plywood) that had been laid on the floor and set up as a
wall at the end of the barn. B. atrophaeus subsp. globigii spores were found to
remain airborne for significantly longer periods, and to be deposited on
horizontal surfaces at lower densities, than Btcry- spores, particularly near the
spray source. There was a 6-fold-higher deposition of Btcry- spores than of B.
atrophaeus subsp. globigii spores on vertical surfaces relative to the
surrounding airborne density. This work is relevant for selecting the best B.
anthracis surrogate for the prediction of human exposure, hazard assessment, and
hazard management following a malicious release of B. anthracis IMPORTANCE: There
is concern that pathogenic bacteria could be maliciously disseminated in the air
to cause human infection and disruption of normal life. The threat from spore
forming organisms, such as the causative agent of anthrax, is particularly
serious. In order to assess the extent of this risk, it is important to have a
surrogate organism that can be used to replicate the dispersal characteristics of
the threat agent accurately. This work compares the aerosol dispersal and
deposition behaviors of the surrogates Btcry- and B. atrophaeus subsp. globigii
Btcry- spores remained in the air for a shorter time, and were markedly more
likely to adhere to vertical surfaces, than B. atrophaeus subsp. globigii spores.
PMID- 27613682
TI - Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg)
with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by
Engineering the Substrate Entrance Tunnel.
AB - : Promiscuous enzymes are generally considered to be starting points in the
evolution of offspring enzymes with more specific or even novel catalytic
activities, which is the molecular basis of producing new biological functions.
Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both
gamma-lactamase and perhydrolase activities. However, despite having high
structural similarity to and sharing an identical catalytic triad with an
extensively studied esterase from Pseudomonas fluorescens, this enzyme did not
show any esterase activity. Molecular docking and sequence analysis suggested a
possible role for the entry of the binding pocket in blocking the entrance
tunnel, preventing the ester compounds from entering into the pocket. By
engineering the entrance tunnel with only one or two amino acid substitutions, we
successfully obtained five esterase variants of Mhg. The variants exhibited a
very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol
esters but also various types of chiral esters, which are widely used as drug
intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal
role in modulating the three catalytic activities by adjusting the size and shape
of the tunnel, with different amino acid substitutions at this site facilitating
different activities. Remarkably, the variant with the L233G mutation was a very
specific esterase without any gamma-lactamase and perhydrolase activities.
Considering the amino acid conservation and differentiation, this site could be a
key target for future protein engineering. In addition, we demonstrate that
engineering the entrance tunnel is an efficient strategy to regulate enzyme
catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting
points in the evolution of novel catalytic activities, thus providing a molecular
basis for the production of new biological functions. In this study, we
identified a critical amino acid residue (Leu233) at the entry of the substrate
tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue
with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with
novel esterase activity. Different amino acids at this site can facilitate
different catalytic activities. These findings exhibited universal significance
in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we
demonstrate that engineering the entrance tunnel is an efficient strategy to
evolve new enzyme catalytic capabilities. Our study has important implications
for the regulation of enzyme catalytic promiscuity and development of protein
engineering methodologies.
PMID- 27613683
TI - Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host
Immune Function and Reduces Nosema ceranae Infections.
AB - : Nosema ceranae is a new and emerging microsporidian parasite of European honey
bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA
interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged
as a potent and specific strategy for controlling infections of parasites and
pathogens in honey bees. While previous studies have focused on the silencing of
parasite/pathogen virulence factors, we explore here the possibility of silencing
a host factor as a mechanism for reducing parasite load. Specifically, we used an
RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd),
which is a negative regulator of host immune function. Our studies found that nkd
mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the
parasite may use this mechanism to suppress host immune function) and that
ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its
expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts
in Nosema-infected bees resulted in upregulation of the expression of several
immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema
spore loads, and extension of honey bee life span. The results of our studies
clearly indicate that silencing the host nkd gene can activate honey bee immune
responses, suppress the reproduction of N. ceranae, and improve the overall
health of honey bees. This study represents a novel host-derived therapeutic for
honey bee disease treatment that merits further exploration. IMPORTANCE: Given
the critical role of honey bees in the pollination of agricultural crops, it is
urgent to develop strategies to prevent the colony decline induced by the
infection of parasites/pathogens. Targeting parasites and pathogens directly by
RNAi has been proven to be useful for controlling infections in honey bees, but
little is known about the disease impacts of RNAi silencing of host factors.
Here, we demonstrate that knocking down the honey bee immune repressor-encoding
nkd gene can suppress the reproduction of N. ceranae and improve the overall
health of honey bees, which highlights the potential role of host-derived and
RNAi-based therapeutics in controlling the infections in honey bees. The
information obtained from this study will have positive implications for honey
bee disease management practices.
PMID- 27613684
TI - Epithelial Coculture and l-Lactate Promote Growth of Helicobacter cinaedi under
H2-Free Aerobic Conditions.
AB - : Helicobacter cinaedi is an emerging opportunistic pathogen associated with
infections of diverse anatomic sites. Nevertheless, the species demonstrates
fastidious axenic growth; it has been described as requiring a microaerobic
atmosphere, along with a strong preference for supplemental H2 gas. In this
context, we examined the hypothesis that in vitro growth of H. cinaedi could be
enhanced by coculture with human epithelial cells. When inoculated (in Ham's F12
medium) over Caco-2 monolayers, the type strain (ATCC BAA-847) gained the ability
to proliferate under H2-free aerobic conditions. Identical results were observed
during coculture with several other monolayer types (LS-174T, AGS, and HeLa).
Under chemically defined conditions, 40 amino acids and carboxylates were
screened for their effect on the organism's atmospheric requirements. Several
molecules promoted H2-free aerobic proliferation, although it occurred most
prominently with millimolar concentrations of l-lactate. The growth response of
H. cinaedi to Caco-2 cells and l-lactate was confirmed with a collection of 12
human-derived clinical strains. mRNA sequencing was next performed on the type
strain under various growth conditions. In addition to providing a whole
transcriptome profile of H. cinaedi, this analysis demonstrated strong
constitutive expression of the l-lactate utilization locus, as well as
differential transcription of terminal respiratory proteins as a function of Caco
2 coculture and l-lactate supplementation. Overall, these findings challenge
traditional views of H. cinaedi as an obligate microaerophile. IMPORTANCE: H.
cinaedi is an increasingly recognized pathogen in people with compromised immune
systems. Atypical among other members of its bacterial class, H. cinaedi has been
associated with infections of diverse anatomic sites. Growing H. cineadi in the
laboratory is quite difficult, due in large part to the need for a specialized
atmosphere. The suboptimal growth of H. cinaedi is an obstacle to clinical
diagnosis, and it also limits investigation into the organism's biology. The
current work shows that H. cinaedi has more flexible atmospheric requirements in
the presence of host cells and a common host-derived molecule. This nutritional
interplay raises new questions about how the organism behaves during human
infections and provides insights for how to optimize its laboratory cultivation.
PMID- 27613685
TI - Benefits of a Recombination-Proficient Escherichia coli System for Adaptive
Laboratory Evolution.
AB - : Adaptive laboratory evolution typically involves the propagation of organisms
asexually to select for mutants with the desired phenotypes. However, asexual
evolution is prone to competition among beneficial mutations (clonal
interference) and the accumulation of hitchhiking and neutral mutations. The
benefits of horizontal gene transfer toward overcoming these known disadvantages
of asexual evolution were characterized in a strain of Escherichia coli
engineered for superior sexual recombination (genderless). Specifically, we
experimentally validated the capacity of the genderless strain to reduce the
mutational load and recombine beneficial mutations. We also confirmed that
inclusion of multiple origins of transfer influences both the frequency of
genetic exchange throughout the chromosome and the linkage of donor DNA. We built
a simple kinetic model to estimate recombination frequency as a function of
transfer size and relative genotype enrichment in batch transfers; the model
output correlated well with the experimental data. Our results provide strong
support for the advantages of utilizing the genderless strain over its asexual
counterpart during adaptive laboratory evolution for generating beneficial
mutants with reduced mutational load. IMPORTANCE: Over 80 years ago Fisher and
Muller began a debate on the origins of sexual recombination. Although many
aspects of sexual recombination have been examined at length, experimental
evidence behind the behaviors of recombination in many systems and the means to
harness it remain elusive. In this study, we sought to experimentally validate
some advantages of recombination in typically asexual Escherichia coli and
determine if a sexual strain of E. coli can become an effective tool for strain
development.
PMID- 27613686
TI - Human-Associated Bacteroides spp. and Human Polyomaviruses as Microbial Source
Tracking Markers in Hawaii.
AB - : Identification of sources of fecal contaminants is needed to (i) determine the
health risk associated with recreational water use and (ii) implement appropriate
management practices to mitigate this risk and protect the environment. This
study evaluated human-associated Bacteroides spp. (HF183TaqMan) and human
polyomavirus (HPyV) markers for host sensitivity and specificity using human and
animal fecal samples collected in Hawaii. The decay rates of those markers and
indicator bacteria were identified in marine and freshwater microcosms exposed
and not exposed to sunlight, followed by field testing of the usability of the
molecular markers. Both markers were strongly associated with sewage, although
the cross-reactivity of the HF183TaqMan (also present in 82% of canine [n = 11],
30% of mongoose [n = 10], and 10% of feline [n = 10] samples) needs to be
considered. Concentrations of HF183TaqMan in human fecal samples exceeded those
in cross-reactive animals at least 1,000-fold. In the absence of sunlight, the
decay rates of both markers were comparable to the die-off rates of enterococci
in experimental freshwater and marine water microcosms. However, in sunlight, the
decay rates of both markers were significantly lower than the decay rate of
enterococci. While both markers have their individual limitations in terms of
sensitivity and specificity, these limitations can be mitigated by using both
markers simultaneously; ergo, this study supports the concurrent use of
HF183TaqMan and HPyV markers for the detection of sewage contamination in coastal
and inland waters in Hawaii. IMPORTANCE: This study represents an in-depth
characterization of microbial source tracking (MST) markers in Hawaii. The
distribution and concentrations of HF183TaqMan and HPyV markers in human and
animal fecal samples and in wastewater, coupled with decay data obtained from
sunlight-exposed and unexposed microcosms, support the concurrent application of
HF183TaqMan and HPyV markers for sewage contamination detection in Hawaii waters.
Both markers are more conservative and more specific markers of sewage than fecal
indicator bacteria (enterococci and Escherichia coli). Analysis of HF183TaqMan
(or newer derivatives) is recommended for inclusion in future epidemiological
studies concerned with beach water quality, while better concentration techniques
are needed for HPyV. Such epidemiological studies can be used to develop new
recreational water quality criteria, which will provide direct information on the
absence or presence of sewage contamination in water samples as well as reliable
measurements of the risk of waterborne disease transmission to swimmers.
PMID- 27613687
TI - Expression of Surface Protein LapB by a Wide Spectrum of Listeria monocytogenes
Serotypes as Demonstrated with Anti-LapB Monoclonal Antibodies.
AB - : Protein antigens expressed on the surface of all strains of Listeria
monocytogenes and absent from nonpathogenic Listeria spp. are presumably useful
targets for pathogen identification, detection, and isolation using specific
antibodies (Abs). To seek such surface proteins expressed in various strains of
L. monocytogenes for diagnostic applications, we focused on a set of surface
proteins known to be involved or putatively involved in L. monocytogenes
virulence and identified Listeria adhesion protein B (LapB) as a candidate based
on the bioinformatics analysis of whole-genome sequences showing that the gene
coding for LapB was present in L. monocytogenes strains and absent from strains
of other Listeria spp. Immunofluorescence microscopy (IFM), performed with rabbit
polyclonal antibodies against the recombinant LapB protein (rLapB) of L.
monocytogenes serotype 4b strain L10521, confirmed expression of LapB on the
surface. A panel of 48 mouse monoclonal antibodies (MAbs) to rLaB was generated,
and 7 of them bound strongly to the surface of L. monocytogenes cells as
demonstrated using IFM. Further characterization of these 7 anti-LapB MAbs, using
an enzyme-linked immunosorbent assay (ELISA), revealed that 6 anti-LapB MAbs
(M3484, M3495, M3500, M3509, M3517, and M3519) reacted strongly with 46 (86.8%)
of 53 strains representing 10 of the 12 serotypes tested (1/2a, 1/2b, 1/2c, 3a,
3b, 3c, 4ab, 4b, 4d, and 4e). These results indicate that LapB, together with
companion anti-LapB MAbs, can be targeted as a biomarker for the detection and
isolation of various L. monocytogenes strains from contaminated foods.
IMPORTANCE: Strains of L. monocytogenes are traditionally grouped into serotypes.
Identification of a surface protein expressed in all or the majority of at least
12 serotypes would aid in the development of surface-binding monoclonal
antibodies (MAbs) for detection and isolation of L. monocytogenes from foods.
Bioinformatics analysis revealed that the gene coding for Listeria adhesion
protein B (LapB), a surface protein involved in L. monocytogenes virulence, was
present in L. monocytogenes strains and absent from other Listeria spp.
Polyclonal antibodies against recombinant LapB (rLapB) detected the exposed
epitopes on the surface of L. monocytogenes Production and extensive assessment
of 48 MAbs to rLapB showed that 6 anti-LapB MAbs (M3484, M3495, M3500, M3509,
M3517, and M3519) detected the expression of LapB in a wide range of L.
monocytogenes isolates representing 10 of 12 serotypes tested, suggesting that
LapB, together with specific MAbs, can be targeted as a biomarker for pathogen
detection and isolation.
PMID- 27613688
TI - Genomic Analysis of Salmonella enterica Serovar Typhimurium from Wild Passerines
in England and Wales.
AB - : Passerine salmonellosis is a well-recognized disease of birds in the order
Passeriformes, which includes common songbirds such as finches and sparrows,
caused by infection with Salmonella enterica serovar Typhimurium. Previous
research has suggested that some subtypes of S Typhimurium-definitive phage types
(DTs) 40, 56 variant, and 160-are host adapted to passerines and that these birds
may represent a reservoir of infection for humans and other animals. Here, we
have used the whole-genome sequences of 11 isolates from British passerines, five
isolates of similar DTs from humans and a domestic cat, and previously published
S Typhimurium genomes that include similar DTs from other hosts to investigate
the phylogenetic relatedness of passerine salmonellae to other S Typhimurium
isolates and investigate possible genetic features of the distinct disease
pathogenesis of S Typhimurium in passerines. Our results demonstrate that the 11
passerine isolates and 13 other isolates, including those from nonpasserine
hosts, were genetically closely related, with a median pairwise single nucleotide
polymorphism (SNP) difference of 130 SNPs. These 24 isolates did not carry
antimicrobial resistance genetic determinants or the S Typhimurium virulence
plasmid. Although our study does not provide evidence of Salmonella transmission
from passerines to other hosts, our results are consistent with the hypothesis
that wild birds represent a potential reservoir of these Salmonella subtypes, and
thus, sensible personal hygiene precautions should be taken when feeding or
handling garden birds. IMPORTANCE: Passerine salmonellosis, caused by certain
definitive phage types (DTs) of Salmonella Typhimurium, has been documented as a
cause of wild passerine mortality since the 1950s in many countries, often in the
vicinity of garden bird feeding stations. To gain better insight into its
epidemiology and host-pathogen interactions, we sequenced the genomes of a
collection of 11 isolates from wild passerine salmonellosis in England and Wales.
Phylogenetic analysis showed these passerine isolates to be closely related to
each other and to form a clade that is distinct from other strains of S
Typhimurium, which included a multidrug-resistant isolate from invasive
nontyphoidal Salmonella disease that shares the same phage type as several of the
passerine isolates. Closely related to wild passerine isolates and within the
same clade were four S Typhimurium isolates from humans as well as isolates from
horses, poultry, cattle, an unspecified wild bird, and a domestic cat and dog
with similar DTs and/or multilocus sequence types. This suggests the potential
for cross-species transmission, and the genome sequences provide a valuable
resource to investigate passerine salmonellosis further.
PMID- 27613690
TI - Including Underrepresented Subgroups of Smokers in Tobacco Regulation Research.
PMID- 27613689
TI - Function and Phylogeny of Bacterial Butyryl Coenzyme A:Acetate Transferases and
Their Diversity in the Proximal Colon of Swine.
AB - : Studying the host-associated butyrate-producing bacterial community is
important, because butyrate is essential for colonic homeostasis and gut health.
Previous research has identified the butyryl coenzyme A (CoA):acetate-CoA
transferase (EC 2.3.8.3) as a gene of primary importance for butyrate production
in intestinal ecosystems; however, this gene family (but) remains poorly defined.
We developed tools for the analysis of butyrate-producing bacteria based on 12
putative but genes identified in the genomes of nine butyrate-producing bacteria
obtained from the swine intestinal tract. Functional analyses revealed that eight
of these genes had strong But enzyme activity. When but paralogues were found
within a genome, only one gene per genome encoded strong activity, with the
exception of one strain in which no gene encoded strong But activity. Degenerate
primers were designed to amplify the functional but genes and were tested by
amplifying environmental but sequences from DNA and RNA extracted from swine
colonic contents. The results show diverse but sequences from swine-associated
butyrate-producing bacteria, most of which clustered near functionally confirmed
sequences. Here, we describe tools and a framework that allow the bacterial
butyrate-producing community to be profiled in the context of animal health and
disease. IMPORTANCE: Butyrate is a compound produced by the microbiota in the
intestinal tracts of animals. This compound is of critical importance for
intestinal health, and yet studying its production by diverse intestinal bacteria
is technically challenging. Here, we present an additional way to study the
butyrate-producing community of bacteria using one degenerate primer set that
selectively targets genes experimentally demonstrated to encode butyrate
production. This work will enable researchers to more easily study this very
important bacterial function that has implications for host health and resistance
to disease.
PMID- 27613695
TI - Is beta-cell aging involved in the pathogenesis of diabetes?
AB - BACKGROUND: beta-Cells at different stages have different functions and capacity
for proliferation, regenerative and apoptosis. The aim of the present study was
to investigate whether there are changes in beta-cell phonotype in the
development of diabetes to identify potential beta-cell targets to prevent the
progression of diabetes. METHODS: A cross-sectional study was performed on
pancreatic tissues obtained from 80 patients classified into three groups: 25
with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non
diabetics (ND). The ratio of the insulin-positive area to pancreatic area was
used as an indirect marker of beta-cell mass. Insulin-positive duct cells and
scattered beta-cells were defined as newly generated beta-cells, whereas
insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma
oncogene family, protein A (MafA) and insulin/P16 double-positive cells were
defined as immature, mature, and senescent beta-cells, respectively; Ki67 was
used as a marker of cell proliferation, and terminal deoxyribonucleotidyl
transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a
marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test.
RESULTS: There were no significant differences in beta-cell mass, the prevalence
of insulin-positive duct cells, scattered beta-cells, or insulin/Ngn3,
insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence
of insulin/P16 double-positive cells was significantly higher in T2D than ND.
beta-Cell apoptosis was significantly higher in T2D and IFG than ND. CONCLUSION:
The senescence and apoptosis of beta-cells may be involved in the course of
diabetes.
PMID- 27613696
TI - Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species-Induced
Mouse Model.
AB - Systemic sclerosis (SSc) is a connective tissue disorder characterized by
fibrosis of the skin and inner organs, vasculopathy, and immunological
abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/beta
catenin in fibrosis have prompted us to investigate, in a mouse model of ROS
induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both
of these signaling pathways. SSc was induced in BALB/c mice by daily s.c.
injections of hypochlorous acid (HOCl). Mice were treated or not every other day,
5 d a week, for 6 wk, by niclosamide. Skin and lung fibrosis as well as
immunological features were studied. Mice exposed to HOCl developed a diffuse
cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1
autoantibodies. STAT3, AKT, and Wnt/beta-catenin pathways were hyperactivated in
the skin and the lungs of diseased mice. Niclosamide reversed fibrosis of the
skin and the lungs. Beneficial immunological effects were also observed because
niclosamide decreased the activation of CD4+ and CD8+ T cells, autoimmune B cell
activation, as well as IL-4 and IL-13 production in the skin. The improvement
permitted by niclosamide in the mouse model of HOCl-induced SSc as well as the
well-documented safety profile of this drug provide a rationale for the
evaluation of niclosamide in the management of patients affected by this disease.
PMID- 27613697
TI - Context-Specific Function of S6K2 in Th Cell Differentiation.
AB - The mammalian target of rapamycin (mTOR) is essential for Th cell proliferation
and effector differentiation, making the mTOR signaling network an attractive
immunomodulatory target for autoimmune-related diseases. Although direct
targeting of mTOR complex-1 (mTORC1) with rapamycin can provide clinical benefit,
targeting downstream enzymes has the potential to offer more selective
immunosuppression. In this study, we evaluated p70 ribosomal protein S6 Kinase 2
(S6K2), a downstream effector of mTORC1, for its role in T cell function and
autoimmunity. S6K2 is a direct substrate of mTORC1, with a potential role in Th17
differentiation suggested by biochemical studies. Using a genetic approach with
S6K2 knockout mice, we found that S6K2 loss reduces Th17 skewing and increases
regulatory T cell differentiation in vitro when cultured in RPMI 1640 media.
However, S6K2 was dispensable for Th17 differentiation in IMDM. In an in vivo
experimental autoimmune encephalomyelitis model in which rapamycin suppresses
disease, S6K2 knockout mice did not exhibit differences in clinical score or Th17
differentiation. These results suggest that S6K2 is dispensable for Th17-driven
autoimmunity and highlight how distinct experimental conditions can produce
significantly different results in T cell differentiation.
PMID- 27613698
TI - An Ectopic CTCF Binding Element Inhibits Tcrd Rearrangement by Limiting Contact
between Vdelta and Ddelta Gene Segments.
AB - Chromatin looping mediated by the CCCTC binding factor (CTCF) regulates V(D)J
recombination at Ag receptor loci. CTCF-mediated looping can influence
recombination signal sequence (RSS) accessibility by regulating enhancer
activation of germline promoters. CTCF-mediated looping has also been shown to
limit directional tracking of the RAG recombinase along chromatin, and to
regulate long-distance interactions between RSSs, independent of the RAG
recombinase. However, in all prior instances in which CTCF-mediated looping was
shown to influence V(D)J recombination, it was not possible to fully resolve the
relative contributions to the V(D)J recombination phenotype of changes in
accessibility, RAG tracking, and RAG-independent long-distance interactions. In
this study, to assess mechanisms by which CTCF-mediated looping can impact V(D)J
recombination, we introduced an ectopic CTCF binding element (CBE) immediately
downstream of Edelta in the murine Tcra-Tcrd locus. The ectopic CBE impaired
inversional rearrangement of Trdv5 in the absence of measurable effects on Trdv5
transcription and chromatin accessibility. The ectopic CBE also limited
directional RAG tracking from the Tcrd recombination center, demonstrating that a
single CBE can impact the distribution of RAG proteins along chromatin. However,
such tracking cannot account for Trdv5-to-Trdd2 inversional rearrangement.
Rather, the defect in Trdv5 rearrangement could only be attributed to a
reconfigured chromatin loop organization that limited RAG-independent contacts
between the Trdv5 and Trdd2 RSSs. We conclude that CTCF can regulate V(D)J
recombination by segregating RSSs into distinct loop domains and inhibiting RSS
synapsis, independent of any effects on transcription, RSS accessibility, and RAG
tracking.
PMID- 27613700
TI - [68Ga]Pentixafor-Positron Emission Tomography/Computed Tomography Detects
Chemokine Receptor CXCR4 Expression After Ischemic Stroke.
PMID- 27613701
TI - When Virchow Meets Da Vinci: Correlating Thrombogenesis With Intracardiac Flow
Dynamics.
PMID- 27613699
TI - Left Atrial and Left Atrial Appendage 4D Blood Flow Dynamics in Atrial
Fibrillation.
AB - BACKGROUND: Atrial 4D flow magnetic resonance imaging was used for the
characterization of left atrial (LA) and left atrial appendage (LAA) flow
dynamics in patients with atrial fibrillation (AF). METHODS AND RESULTS: 4D flow
magnetic resonance imaging measured in vivo 3D blood flow velocities in 60 AF
patients and 15 controls. Anatomic maps of LA and LAA stasis and velocity were
calculated to quantify atrial peak velocity, mean velocity, and stasis
(velocities <0.1 m/s). In a substudy with 30 AF patients, 4D flow metrics were
compared with Doppler transesophageal echocardiography. For all 15 controls, LAA
mean and peak velocities were consistently lower (by 21%/12%; P<0.001) while LAA
stasis was higher (by 58%; P<0.001) compared with the LA. In contrast, lower LAA
velocity and increased LAA stasis were only found in a fraction (38 of 60) of AF
patients. In AF patients, increased CHA2DS2-VASc score was associated with
significantly (P<0.043) reduced LA velocities and elevated stasis. There was a
heterogeneous expression of atrial flow dynamics, and 25% to 68% of AF patients
demonstrated flow in the normal range: 25%/68% for LA/LAA stasis and 38%/60% for
LA/LAA peak velocities. Transesophageal echocardiography velocities modestly but
significantly (P<0.05) correlated with 4D flow-based LA velocities (r=0.41) and
stasis (r=-0.39). CONCLUSIONS: AF resulted in overall impaired but individually
variable flow dynamics in both the LA and LAA. AF patients demonstrated atrial
flow in the normal range, despite elevated CHA2DS2-VASc score.
PMID- 27613702
TI - Whole body perfusion in patients undergoing frozen elephant trunk for type A
acute aortic dissections.
AB - The Frozen Elephant Trunk (FET) can be adopted in selected type A acute aortic
dissections (TAAAD). During FET, a prolonged distal circulatory arrest exposes
the spine and visceral organs to potential ischemic injuries. Antegrade distal
aortic perfusion (ADAP) could minimize this risk: we describe the technical
aspects of the simultaneous use of antegrade cerebral perfusion (ACP) and ADAP
achieving a "Whole Body Perfusion" (WBP) during FET.
PMID- 27613703
TI - Problems with ethical approval and how to fix them: lessons from three trials in
rheumatoid arthritis.
PMID- 27613704
TI - Linear and urticarial rash-like manifestation of acute strongyloidiasis.
PMID- 27613705
TI - Shielding design for a Cs-137 rod-type standard point source for well chamber
constancy checks.
AB - Well type chambers are used for radioactive source calibrations in brachytherapy,
but do not provide radiation shielding. Routine constancy checks on a well
chamber are required between periodic secondary standard laboratory calibrations
to ensure consistent device performance, and ultimately to ensure accurate
patient dose delivery. In this work, a method is described to provide suitable
shielding for a Cs-137 rod-type point source to enable use for constancy checks.
A novel plunger-type shielded housing was designed and constructed for the Cs-137
source that when combined with a suitably shielded well-chamber container
minimised user exposure during constancy checks. The designed shielding proved
effective, and a constancy test routine was established and used for the past 16
months. The well chamber showed consistent performance (0.12 +/- 0.18 % from the
baseline) and no increased exposure was reported on users' radiation badges.
PMID- 27613706
TI - A joint application of optimal threshold based discrete cosine transform and
ASCII encoding for ECG data compression with its inherent encryption.
AB - In this paper, a joint use of the discrete cosine transform (DCT), and
differential pulse code modulation (DPCM) based quantization is presented for
predefined quality controlled electrocardiogram (ECG) data compression. The
formulated approach exploits the energy compaction property in transformed
domain. The DPCM quantization has been applied to zero-sequence grouped DCT
coefficients that were optimally thresholded via Regula-Falsi method. The
generated sequence is encoded using Huffman coding. This encoded series is
further converted to a valid ASCII code using the standard codebook for
transmission purpose. Such a coded series possesses inherent encryption
capability. The proposed technique is validated on all 48 records of standard MIT
BIH database using different measures for compression and encryption. The
acquisition time has been taken in accordance to that existed in literature for
the fair comparison with contemporary state-of-art approaches. The chosen
measures are (1) compression ratio (CR), (2) percent root mean square difference
(PRD), (3) percent root mean square difference without base (PRD1), (4) percent
root mean square difference normalized (PRDN), (5) root mean square (RMS) error,
(6) signal to noise ratio (SNR), (7) quality score (QS), (8) entropy, (9) Entropy
score (ES) and (10) correlation coefficient (r x,y ). Prominently the average
values of CR, PRD and QS were equal to 18.03, 1.06, and 17.57 respectively.
Similarly, the mean encryption metrics i.e. entropy, ES and r x,y were 7.9692,
0.9962 and 0.0113 respectively. The novelty in combining the approaches is well
justified by the values of these metrics that are significantly higher than the
comparison counterparts.
PMID- 27613708
TI - Five-year publication rate of clinical presentations at the open and closed
American shoulder and elbow surgeons annual meeting from 2005-2010.
AB - BACKGROUND: The purpose of this study was to evaluate the five-year publication
rate of papers presented at both the open and closed American Shoulder and Elbow
Surgeons' (ASES) annual meetings from 2005 to 2010. METHODS: Online abstracts of
the presentations at the open and closed ASES annual meetings were independently
screened for clinical studies and graded for quality using level of evidence. The
databases PubMed (MEDLINE), Ovid (MEDLINE), and EMBASE were comprehensively
searched for full-text publications corresponding to these presentations and any
paper published within five years of the presentation date was counted. RESULTS:
Overall, 131/266 papers corresponding to the meeting presentations were
identified for a five-year publication rate of 49.2 %. Sixty two (48 %) of the
papers were published in The Journal of Shoulder and Elbow Surgeons, 23 (18 %)
were published in The American Journal of Sports Medicine, and 20 (16 %) were
published in The Journal of Bone and Joint Surgery. The mean patient sample size
included in presentations with a subsequent full-text publication was higher
(154; standard error =27) than the presentations not published (93; standard
error = 13) (p = 0.039). There was no correlation (p = 0.248) between the
publication rate and the level of evidence of the presentations. CONCLUSIONS: The
publication rate of presentations at ASES meetings from 2005 to 2010 is similar
to that reported from other orthopaedic meetings. Studies with large sample sizes
should continue to be encouraged, and high quality presentations must
consistently be followed up with full-text manuscript preparation in order to
maximize the future clinical impact.
PMID- 27613707
TI - Maternal pre-pregnancy and gestational diabetes, obesity, gestational weight
gain, and risk of cancer in young children: a population-based study in
California.
AB - PURPOSE: We aimed to examine the influence of pre-pregnancy diabetes, pre
pregnancy body mass index (BMI), gestational diabetes, and gestational weight
gain on childhood cancer risk in offspring. METHODS: We identified cancer cases
(n = 11,149) younger than age 6 years at diagnosis from the California Cancer
Registry registered between 1988 and 2013. Controls (n = 270,147) were randomly
sampled from California birth records, and frequency matched by year of birth to
all childhood cancers during the study period. Exposure and covariate information
were extracted from birth records. Unconditional logistic regression models were
generated to assess the importance of pre-pregnancy diabetes, pre-pregnancy BMI,
gestational diabetes, and gestational weight gain on childhood cancer risk.
RESULTS: We observed increased risks of acute lymphoblastic leukemia and Wilms'
tumor in children of mothers with pre-pregnancy diabetes [odds ratio (OR) 95 %
confidence interval (CI) 1.37 (1.11, 1.69); OR (95 % CI) 1.45 (0.97, 2.18),
respectively]. When born to mothers who were overweight prior to pregnancy (BMI
25-<30), children were at increased risk of leukemia [OR (95 % CI) 1.27 (1.01,
1.59)]. Insufficient gestational weight gain increased the risk of acute myeloid
leukemia [OR (95 % CI) 1.50 (0.92, 2.42)] while excessive gestational weight gain
increased the risk of astrocytomas [OR (95 % CI) 1.56 (0.97, 2.50)]. No
associations were found between gestational diabetes and childhood cancer risk in
offspring. CONCLUSIONS: We estimated elevated risks of several childhood cancers
in the offspring of mothers who had diabetes and were overweight prior to
pregnancy, as well as mothers who gained insufficient or excessive weight. Since
few studies have focused on these factors in relation to childhood cancer,
replication of our findings in future studies is warranted.
PMID- 27613709
TI - Hip dysplasia in the young adult caused by residual childhood and adolescent
onset dysplasia.
AB - Hip dysplasia is a treatable developmental disorder that presents early in life
but if neglected can lead to chronic disability due to pain, decreased function,
and early osteoarthritis. The main causes of hip dysplasia in the young adult are
residual childhood developmental dysplasia of the hip (DDH) and adolescent-onset
acetabular dysplasia. These two distinct disease processes affect the growing hip
during different times of development but result in a similar deformity and
pathomechanism of hip degeneration. Routine screening for DDH and counseling
regarding risks for acetabular dysplasia in families with a history of early hip
osteoarthritis may allow early identification and intervention in these hips with
anatomical risk factors for joint degeneration.
PMID- 27613710
TI - Towards an understanding of the painful total knee: what is the role of patient
biology?
AB - Total knee arthroplasty (TKA) remains the treatment of choice for end-stage
osteoarthritis of the knee. With an aging population, the demand for TKA
continues to increase, placing a significant burden on a health care system that
must function with limited resources. Although generally accepted as a successful
procedure, 15-30 % of patients report persistent pain following TKA. Classically,
pain generators have been divided into intra-articular and extra-articular
causes. However, there remains a significant subset of patients for whom pain
remains unexplained. Recent studies have questioned the role of biology
(inflammation) in the persistence of pain following TKA. This article aims to
serve as a review of previously identified causes of knee pain following TKA, as
well as to explore the potential role of biology as a predictor of pain following
knee replacement surgery.
PMID- 27613711
TI - Psychosocial difficulties in patients with episodic migraine: a cross-sectional
study.
AB - To explore the relationships between psychosocial difficulties (PSDs), quality of
life (QoL), and disability and to explore the degree to which PSDs can be
predicted by demographic variables, clinical variables, and risk and protective
factors. Patients with episodic migraine completed a protocol inclusive of
PARADISE 24 questionnaire (the 24-item Psychosocial Difficulties Relevant to
Brain Disorders questionnaire), a new questionnaire that captures PSDs relevant
to brain disorders, and assessments of disability, QoL, disease severity,
presence of comorbidities, social support, and clinical and risk factors (i.e.,
smoking and body mass index). Spearman's correlation was used to address the
relationship between PARADISE 24, and the assessments of disability and QoL;
multivariable linear regression analysis was carried out to address PARADISE 24
predictors. Eighty patients were enrolled (86.3 % females, mean age 44.5).
PARADISE 24 was well correlated with disability (rho = 0.787) and moderately with
QoL (rho = -0.526). The regression analysis shows that younger age, higher
migraine frequency, higher comorbidities index and being a smoker were predictors
of PARADISE 24 (R 2: 0.470). Addressing the burden associated with PSDs in
migraineurs is important as these might be the reason why patients look for
specialists in headache disorders. PARADISE 24 represents a viable way to address
patients' difficulties in daily practice.
PMID- 27613712
TI - Pathophysiology underlying drooling in Parkinson's disease: oropharyngeal
bradykinesia.
AB - We aimed to investigate the association between drooling and possible etiological
factors in Parkinson's disease (PD) and to determine its effect on the quality of
life. Demographic data of the 63 patients with idiopathic PD were recorded.
Radboud Oral Motor Inventory for Parkinson's disease (ROMP) test was administered
to all patients to evaluate speech, swallowing functions, and saliva control. The
freezing of gait questionnaire (FOGQ) was used to evaluate gait and freezing of
gait. Dynamic Parkinson gait scale (DYPAGS) was administered for the objective
quantification of PD gait features. Disease severity was assessed by UPDRS and
modified Hoehn & Yahr Scale. PD specific health-related quality was evaluated by
PDQ-39 questionnaire. Drooling was only significantly correlated to UPDRS score;
a stronger association was found between drooling and UPDRS 3 motor score; and a
more significant association was determined between drooling and the bradykinesia
questions of the motor part of UPDRS 3. Interestingly, no significant association
was found between sialorrhea score and PDQ-39 score. Based on the results of this
study, we concluded that oropharyngeal bradykinesia may be responsible for
drooling in PD. In contrast to a general expectation, we did not find any adverse
impact of drooling on the quality of life.
PMID- 27613714
TI - Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5
Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose,
Route, and Repeated Administration.
AB - 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW 549.92 g/mol; CAS 183658-27
7) is a brominated component of flame retardant mixtures used as substitutes for
some PBDEs. EH-TBB is added to various consumer products, including polyurethane
foams, and has been detected in humans. The present study characterized the fate
of EH-TBB in rodents. [14C]-labeled EH-TBB was absorbed, metabolized, and
eliminated via the urine and feces following single administrations of 0.1-100
umol/kg (~0.05-55 mg/kg) or repeated administration (0.1 umol/kg/day * 5-10 days)
by gavage to female Hsd:Sprague DawleySD (SD) rats. Cumulative excretion via
feces increased (39-60%) with dose (0.1-10 umol/kg) with corresponding decreases
in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [14C]
radioactivity in urine and feces of a 100 umol/kg oral dose was noted. Recovery
was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1
umol/kg dose in urine and less in feces than did gavaged rats, indicating partial
biliary elimination of systemically available compound. No tissue bioaccumulation
was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not
detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA
sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA
were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice
indicated minimal sex- or species differences are likely for the disposition of
EH-TBB. Approximately 85% of a 0.1 umol/kg dose was absorbed from the gut.
Overall absorption of EH-TBB is expected to be even greater at lower levels.
PMID- 27613713
TI - From the Cover: Coagulation-Driven Hepatic Fibrosis Requires Protease Activated
Receptor-1 (PAR-1) in a Mouse Model of TCDD-Elicited Steatohepatitis.
AB - Emerging evidence supports a role for environmental chemical exposure in the
pathology of non-alcoholic fatty liver disease (NAFLD), a disease process tightly
linked to increased activity of the blood coagulation cascade. Exposure of
C57BL/6 mice to the persistent environmental contaminant 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD) recapitulates features of the NAFLD spectrum,
including steatosis, hepatic injury, inflammation, and fibrosis. We assessed
coagulation cascade activation, and determined the role of the thrombin receptor
protease activated receptor-1 (PAR-1) in experimental TCDD-elicited NAFLD.
Chronic exposure to TCDD (30 ug/kg every 4 days for 28 days) was associated with
intrahepatic coagulation, indicated by increased plasma thrombin-antithrombin
levels and hepatic fibrin(ogen) deposition. PAR-1 deficiency diminished TCDD
elicited body weight loss and relative liver weight was reduced in TCDD-exposed
PAR-1-/- mice compared with TCDD-exposed wild-type mice. PAR-1 deficiency did not
affect TCDD-induced hepatic steatosis or hepatocellular injury, as indicated by
serum alanine aminotransferase activity. Despite a lack of effect on these 2
features of NAFLD pathology, PAR-1 deficiency was associated with a reduction in
hepatic inflammation evident in liver histopathology, and reflected by a
reduction in serum levels of the proinflammatory cytokine interleukin-6.
Moreover, TCDD-driven hepatic collagen deposition was markedly reduced in PAR-1
deficient mice. These results indicate that experimental TCDD-elicited
steatohepatitis is associated with coagulation cascade activation and PAR-1
driven hepatic inflammation and fibrosis.
PMID- 27613715
TI - Endoplasmic Reticulum Stress Induction and ERK1/2 Activation Contribute to
Nefazodone-Induced Toxicity in Hepatic Cells.
AB - Nefazodone, an antagonist for the 5-hydroxytryptanine receptor, has been used for
the treatment of depression. Acute liver injury has been documented to be
associated with the use of nefazodone; however, the mechanisms of nefazodone
induced liver toxicity are not well defined. In this report, using biochemical
and molecular analyses, we characterized the molecular mechanisms underlying the
hepatotoxicity of nefazodone. We found that nefazodone induced endoplasmic
reticulum (ER) stress in HepG2 cells, as the expression of typical ER stress
markers, including CHOP, ATF-4, and p-eIF2alpha, was significantly increased, and
splicing of XBP1 was observed. Nefazodone-suppressed protein secretion was
evaluated using a Gaussia luciferase reporter assay that measures ER stress. The
ER stress inhibitors (4-phenylbutyrate and salubrinal) and knockdown of ATF-4
gene attenuated nefazodone-induced ER stress and cytotoxicity. Nefazodone
activated the MAPK signaling pathway, as indicated by increased phosphorylation
of JNK, ERK1/2, and p38. Inhibition of ERK1/2 reduced ER stress caused by
nefazodone. Taken together, our findings suggest that ER stress contributes to
nefazodone-induced toxicity in HepG2 cells and that the MAPK signaling pathway
plays an important role in ER stress.
PMID- 27613717
TI - E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and
Cell Death in Vascular Endothelial Cells.
AB - Cigarette smoking remains one of the leading causes of preventable death
worldwide. Vascular cell death and dysfunction is a central or exacerbating
component in the majority of cigarette smoking related pathologies. The recent
development of the electronic nicotine delivery systems known as e-cigarettes
provides an alternative to conventional cigarette smoking; however, the potential
vascular health risks of e-cigarette use remain unclear. This study evaluates the
effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke
extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory
apparatus was designed to produce extracts from e-cigarettes and conventional
cigarettes according to established protocols for cigarette smoking. EAE or
conventional CSE was applied to human vascular endothelial cells for 4-72 h,
dependent on the assay. Treated cells were assayed for reactive oxygen species,
DNA damage, cell viability, and markers of programmed cell death pathways.
Additionally, the anti-oxidants alpha-tocopherol and n-acetyl-l-cysteine were
used to attempt to rescue e-cigarette induced cell death. Our results indicate
that e-cigarette aerosol is capable of inducing reactive oxygen species, causing
DNA damage, and significantly reducing cell viability in a concentration
dependent fashion. Immunofluorescent and flow cytometry analysis indicate that
both the apoptosis and programmed necrosis pathways are triggered by e-cigarette
aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue
of the induced cell death, indicating that reactive oxygen species play a causal
role in e-cigarette induced cytotoxicity.
PMID- 27613716
TI - Transient Proteotoxicity of Bacterial Virulence Factor Pyocyanin in Renal Tubular
Epithelial Cells Induces ER-Related Vacuolation and Can Be Efficiently Modulated
by Iron Chelators.
AB - Persistent infections of biofilm forming bacteria, such as Pseudomonas
aeruginosa, are common among human populations, due to the bacterial resistance
to antibiotics and other adaptation strategies, including release of cytotoxic
virulent factors such as pigment pyocyanin (PCN). Urinary tract infections harbor
P. aeruginosa strains characterized by the highest PCN-producing capacity, yet no
information is available on PCN cytotoxicity mechanism in kidney. We report here
that renal tubular epithelial cell (RTEC) line NRK-52E responds to PCN treatments
with paraptosis-like activity features. Specifically, PCN-treated cells
experienced dilation of endoplasmic reticulum (ER) and an extensive development
of ER-derived vacuoles after about 8 h. This process was accompanied with hyper
activation of proteotoxic stress-inducible transcription factors Nrf2, ATF6, and
HSF-1. The cells could be rescued by withdrawal of PCN from the culture media
before the vacuoles burst and cells die of non-programmed necrosis after about 24
30 h. The paraptosis-like activity was abrogated by co-treatment of the cells
with metal-chelating antioxidants. A microscopic examination of cells co-treated
with PCN and agents aiming at a variety of the cellular stress mediators and
pathways have identified iron as a single most significant co-factor of the PCN
cytotoxicity in the RTECs. Among biologically relevant metal ions, low micromolar
Fe2+ specifically mediated anaerobic oxidation of glutathione by PCN, but
catechol derivatives and other strong iron complexing agents could inhibit the
reaction. Our data suggest that iron chelation could be considered as a
supplementary treatment in the PCN-positive infections.
PMID- 27613718
TI - Strategy-Based Cognitive Training for Improving Executive Functions in Older
Adults: a Systematic Review.
AB - Given projected increases in dementia prevalence, emphasising earlier stages of
cognitive impairment in older adults enables targeted early intervention
strategies. Strategy-based cognitive training (SCT) is a remedial approach
involving guidance and practice in compensatory techniques to improve cognition,
including memory and attention. It may also be effective for improving executive
functions (EF) integral to everyday tasks. This review systematically evaluates
SCT effects on EF in older adults without dementia. Following PRISMA guidelines,
we reviewed eligible trials according to pre-defined criteria, differentiating
SCT from other cognitive interventions and stipulating total EF-focused
intervention time, study design and target population (healthy older adults or
mild cognitive decline). We then evaluated trials according to design,
methodological quality and outcomes. Unfortunately, with too few studies in mild
cognitive impairment, we refocused our review only on healthy older adults.
Thirteen studies with 4120 participants in total were included, primarily
targeting inductive reasoning. Despite heterogeneous study designs and SCT
programs, 11/13 trials reported significant EF improvements, generally of
moderate effect size (Hedges' g > 0.3). Four studies reported sustained benefits
from one month to 10 years. There was some evidence of far transfer. We conclude
that there is promising evidence for SCT as a targeted intervention for EF in
healthy older adults and preliminary evidence for maintaining effects over time.
Fewer trials have investigated far transfer (e.g. improved everyday functioning)
or capacity to delay/prevent dementia, which are most relevant to clinical
utility. Limitations include the inability to calculate effect sizes for four
studies and absence of statistical meta-analysis.
PMID- 27613720
TI - Low-trauma fractures and bone mineral density testing in adults with and without
intellectual and developmental disabilities: a population study.
AB - : Individuals with intellectual and developmental disabilities (IDD) are at risk
for low-trauma fractures. We investigated the rate of low-trauma fractures and
the odds of BMD testing in adults with/without IDD. Adults with IDD were more
likely to have a low-trauma fracture, but there was no difference in bone mineral
density (BMD) testing rates. INTRODUCTION: Individuals with IDD are at increased
risk for developing osteoporosis which contributes to high rates of low-trauma
fracture. Low-trauma fractures can lead to significant pain and further decrease
mobility. It is therefore important to effectively manage osteoporosis, for
example, by monitoring BMD in persons with IDD. The objective of this study was
to examine the rates of low-trauma fracture and BMD testing among a population
based cohort of people with IDD and compare them to those without IDD. METHODS:
Using administrative data, we created a cohort of adults with IDD between the
ages of 40 and 64. They were compared to a random 20 % sample of those without
IDD. The number of low-trauma fractures and BMD tests in each group were
determined for Ontario residents between April 1, 2009 and March 31, 2010.
RESULTS: Adults with IDD were approximately three times more likely to experience
a low-trauma fracture than adults without IDD. The largest disparity in
prevalence of low-trauma fractures between those with and without IDD was for
men, older adults (60-64 years old) and those living in rural or lower-income
neighbourhoods. Post low-trauma fracture, there was no significant difference in
the likelihood of receiving a BMD test between individuals with and without IDD.
CONCLUSIONS: The findings of this study have a number of important implications
related to early detection, prevention and proper management of osteoporosis and
low-trauma fractures among persons with IDD.
PMID- 27613719
TI - Effects of short-term step aerobics exercise on bone metabolism and functional
fitness in postmenopausal women with low bone mass.
AB - : Measurement of bone turnover markers is an alternative way to determine the
effects of exercise on bone health. A 10-week group-based step aerobics exercise
significantly improved functional fitness in postmenopausal women with low bone
mass, and showed a positive trend in reducing resorption activity via bone
turnover markers. INTRODUCTION: The major goal of this study was to determine the
effects of short-term group-based step aerobics (GBSA) exercise on the bone
metabolism, bone mineral density (BMD), and functional fitness of postmenopausal
women (PMW) with low bone mass. METHODS: Forty-eight PMW (aged 58.2 +/- 3.5
years) with low bone mass (lumbar spine BMD T-score of -2.00 +/- 0.67) were
recruited and randomly assigned to an exercise group (EG) or to a control group
(CG). Participants from the EG attended a progressive 10-week GBSA exercise at an
intensity of 75-85 % of heart rate reserve, 90 min per session, and three
sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1
collagen [CTX] and osteocalcin), BMD, and functional fitness components were
measured before and after the training program. Mixed-models repeated measures
method was used to compare differences between the groups (alpha = 0.05).
RESULTS: After the 10-week intervention period, there was no significant exercise
program by time interaction for CTX; however, the percent change for CTX was
significantly different between the groups (EG = -13.1 +/- 24.4 % vs. CG = 11.0
+/- 51.5 %, P < 0.05). While there was no significant change of osteocalcin in
both groups. As expected, there was no significant change of BMD in both groups.
In addition, the functional fitness components in the EG were significantly
improved, as demonstrated by substantial enhancement in both lower- and upper
limb muscular strength and cardiovascular endurance (P < 0.05). CONCLUSION: The
current short-term GBSA exercise benefited to bone metabolism and general health
by significantly reduced bone resorption activity and improved functional fitness
in PMW with low bone mass. This suggested GBSA could be adopted as a form of
group-based exercise for senior community.
PMID- 27613722
TI - Nuclear histones: major virulence factors or just additional early sepsis
markers? A comment.
AB - In 2009, Xu et al. and Chaput et al. in Nature Medicine had argued that the main
cause of death in sepsis is the release from neutrophil nets of nuclear histone,
highly toxic to endothelial cells and that these polycations are major and unique
virulence factors. Since 2009, numerous researchers have also suggested the
involvement of histones in the pathophysiology of many clinical disorders. If
histones are indeed major unique virulence toxic agents, then heparin, activated
protein C and antibodies to histone should prove excellent antisepsis agents.
However, this is provided that these agents are administered to patients early
enough before the activation of the cytokine storms, immune responses and the
coagulation cascades are irreversibly unleashed. This may not be practical, since
a diagnosis of sepsis is usually made much later. Future identifications of novel
early markers are therefore needed and a compilation of cocktails of antagonists
may replace the faulty single antagonists tried for many years, but in vain, to
prevent death in sepsis.
PMID- 27613723
TI - Helicobacter pylori-induced changes in microtubule dynamics conferred by alpha
tubulin phosphorylation on Ser/Tyr mediate gastric mucosal secretion of matrix
metalloproteinase-9 (MMP-9) and its modulation by ghrelin.
AB - Regulation of matrix metalloproteinase-9 (MMP-9) secretion in response to
proinflammatory challenge remains under a strict control of factors that affect
the stability dynamics of the major cytoskeleton polymeric structures,
microtubules (MTs). In this study, we report that H. pylori LPS-elicited
induction gastric mucosal MMP-9 secretion is accompanied by the enhancement in MT
stabilization as evidenced by the increase in alpha-tubulin acetylation and
detyrosination while the modulatory influence of hormone, ghrelin, is associated
with MT destabilization and reflected in a decrease in alpha-tubulin acetylation
and detyrosination. Further, we reveal that the LPS-induced enhancement in MT
stabilization and up-regulation in MMP-9 secretion as well as the modulatory
influence of ghrelin occur with the involvement of PKCdelta and SFK. The LPS
effect is reflected in a marked increase in PKCdelta-mediated alpha-tubulin
phosphorylation on Ser, while the modulatory effect of ghrelin on MT dynamics and
MMP-9 secretion is manifested by the SFK-dependent phosphorylation of alpha
tubulin on Tyr. Moreover, the changes in alpha-tubulin phosphorylation and MT
stabilization dynamics occur in concert with the Golgi recruitment and activation
of PKD2 and Arf-GEF. The findings demonstrate that the enhancement in gastric
mucosal MMP-9 secretion in response to H. pylori and its modulation by ghrelin
are the result of changes in MT dynamics conferred by PKCdelta/SFK- mediated
alpha-tubulin Ser/Tyr phosphorylation.
PMID- 27613721
TI - Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis,
and management. A Canadian and international consensus.
AB - The purpose of this review is to assess the most recent evidence in the
management of primary hyperparathyroidism (PHPT) and provide updated
recommendations for its evaluation, diagnosis and treatment. A Medline search of
"Hyperparathyroidism. Primary" was conducted and the literature with the highest
levels of evidence were reviewed and used to formulate recommendations. PHPT is a
common endocrine disorder usually discovered by routine biochemical screening.
PHPT is defined as hypercalcemia with increased or inappropriately normal plasma
parathyroid hormone (PTH). It is most commonly seen after the age of 50 years,
with women predominating by three to fourfold. In countries with routine
multichannel screening, PHPT is identified earlier and may be asymptomatic. Where
biochemical testing is not routine, PHPT is more likely to present with skeletal
complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those
with symptomatic disease. For asymptomatic patients, recent guidelines have
recommended criteria for surgery, however PTx can also be considered in those who
do not meet criteria, and prefer surgery. Non-surgical therapies are available
when surgery is not appropriate. This review presents the current state of the
art in the diagnosis and management of PHPT and updates the Canadian Position
paper on PHPT. An overview of the impact of PHPT on the skeleton and other target
organs is presented with international consensus. Differences in the
international presentation of this condition are also summarized.
PMID- 27613725
TI - The growing world of CAR T cell trials: a systematic review.
AB - In recent years, cancer treatment involving adoptive cell therapy with chimeric
antigen receptor (CAR)-modified patient's immune cells has attracted growing
interest. Using gene transfer techniques, the patient's T cells are modified ex
vivo with a CAR which redirects the T cells toward the cancer cells through an
antibody-derived binding domain. The T cells are activated by the CAR primary
signaling and costimulatory domains. Such "second generation" CAR T cells induced
complete remission of B cell malignancies in the long-term. In this fast-moving
field with a growing number of engineered T cell products, we list about 100
currently ongoing trials here that involve CAR T cells targeting hematopoietic
malignancies and solid cancer. Major challenges in the further development of the
therapy are briefly discussed.
PMID- 27613726
TI - Delivery of Essential Medicines to Primary Care Institutions and its Association
with Procurement Volume and Price: A Case Study in Hubei Province, China.
AB - BACKGROUND: The low availability of essential medicines is a worldwide issue of
concern. In 2009, China introduced a National Essential Medicines List (NEML),
with NEML medicines being purchased in bulk at contracted prices established by
tenders conducted at the provincial level. The availability of essential
medicines in the public sector largely relies on commercial supply chains.
OBJECTIVES: The objectives of this paper were to analyze the delivery performance
of essential medicines under NEML provincial procurement arrangements, and to
determine whether the procurement volume and price of medicines are associated
with the delivery performance of suppliers. METHODS: We reviewed 9390 recorded
orders of 1099 essential medicines in Hubei province from August 2011 to April
2012. The reliability of medicine delivery in-full and on-time (DIFOT) was
considered the performance indicator, and we used Spearman correlation analyses
to explore whether there were any associations between DIFOT and procurement
price and volume. Quantile regressions were performed to determine such
associations. RESULTS: The DIFOT had positive correlations with procurement price
and volume. The Spearman rank correlation coefficients between price and DIFOT
were 0.114, 0.34 and 0.25 for medicines with low one-third, middle one-third and
high one-third procurement volumes, respectively. The quantile regression
analysis revealed a positive association between price and DIFOT across all
quantiles of DIFOT, and although significant positive associations between volume
and DIFOT were only found at the 25th percentile of DIFOT, volume showed
significant interactions with price for both the 25th and 50th percentiles of
DIFOT. CONCLUSIONS: Higher procurement price is associated with better delivery
performance of essential medicines; however, it is important to link procurement
price with procurement volume. Increasing procurement volume may alleviate the
negative effect of low price on delivery performance. Variation in volumes of
repeated orders imposes uncertainties and may jeopardize the delivery of
essential medicines.
PMID- 27613724
TI - Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular
rarefaction in the mouse hippocampus and retrosplenial cortex: implications for
cerebromicrovascular and brain aging.
AB - Strong epidemiological and experimental evidence indicate that both age and
hypertension lead to significant functional and structural impairment of the
cerebral microcirculation, predisposing to the development of vascular cognitive
impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal
link between cognitive decline and microvascular rarefaction in the hippocampus,
an area of brain important for learning and memory. Age-related decline in
circulating IGF-1 levels results in functional impairment of the cerebral
microvessels; however, the mechanistic role of IGF-1 deficiency in impaired
hippocampal microvascularization remains elusive. The present study was designed
to characterize the additive/synergistic effects of IGF-1 deficiency and
hypertension on microvascular density and expression of genes involved in
angiogenesis and microvascular regression in the hippocampus. To achieve that
goal, we induced hypertension in control and IGF-1 deficient mice (Igf1 f/f +
TBG-Cre-AAV8) by chronic infusion of angiotensin II. We found that circulating
IGF-1 deficiency is associated with decreased microvascular density and
exacerbates hypertension-induced microvascular rarefaction both in the
hippocampus and the neocortex. The anti-angiogenic hippocampal gene expression
signature observed in hypertensive IGF-1 deficient mice in the present study
provides important clues for subsequent studies to elucidate mechanisms by which
hypertension may contribute to the pathogenesis and clinical manifestation of
VCI. In conclusion, adult-onset, isolated endocrine IGF-1 deficiency exerts
deleterious effects on the cerebral microcirculation, leading to a significant
decline in cortical and hippocampal capillarity and exacerbating hypertension
induced cerebromicrovascular rarefaction. The morphological impairment of the
cerebral microvasculature induced by IGF-1 deficiency and hypertension reported
here, in combination with neurovascular uncoupling, increased blood-brain barrier
disruption and neuroinflammation reported in previous studies likely contribute
to the pathogenesis of vascular cognitive impairment in elderly hypertensive
humans.
PMID- 27613728
TI - Tumor characteristics associated with malignant large bowel obstruction in stage
IV colorectal cancer patients undergoing chemotherapy.
AB - PURPOSE: Little is known about predictable clinical factors associated with the
occurrence of malignant large bowel obstruction (MLBO) in incurable stage IV
colorectal cancer (CRC) patients undergoing medical treatment. This study
investigates the clinical characteristics associated with MLBO that occurred
while patients with stage IV CRC were receiving chemotherapy. METHODS: A total of
216 patients who were diagnosed with stage IV CRC without bowel obstruction and
who received chemotherapy between May 2005 and June 2012 were retrospectively
included in this study. Patients were divided into an "obstruction group" and a
"non-obstruction group" based on whether they did or did not develop MLBO during
chemotherapy or follow-up, respectively. The initial endoscopic findings and
clinical information were retrospectively reviewed and compared between the two
groups. RESULTS: Forty-six patients (21.3 %) developed MLBO during the treatment
or follow-up periods. The mean duration between diagnosis and MLBO was 9.8 +/-
9.3 months. After adjusting for clinically relevant factors, MLBO development was
independently associated with the following factors: higher initial tumor
occupying circumference (HR 1.030 [95 % CI, 1.012-1.049], P = 0.001), longer
initial horizontal tumor width (HR 1.035 [95 % CI, 1.011-1.059], P = 0.004),
primary tumor location at a turning point in the colon (HR 2.404 [95 % CI, 1.185
4.877], P = 0.015), and the presence of primary tumor ulceration at presentation
(HR 3.767 [95 % CI, 1.882-7.538], P < 0.001). MLBO development was not associated
with tumor response to chemotherapy. CONCLUSION: In patients with stage IV CRC,
MLBO development during chemotherapy treatment is associated with tumor
ulceration, location, circumference, and width at diagnosis.
PMID- 27613727
TI - Clinical diagnostic accuracy of acute colonic diverticulitis in patients admitted
with acute abdominal pain, a receiver operating characteristic curve analysis.
AB - PURPOSE: The study investigated the capability of clinical findings, temperature,
C-reactive protein (CRP), and white blood cell (WBC) count to discern patients
with acute colonic diverticulitis from all other patients admitted with acute
abdominal pain. METHODS: The probability of acute diverticulitis was assessed by
the examining doctor, using a scale from 0 (zero probability) to 10 (100 %
probability). Receiver operating characteristic (ROC) curves were used to assess
the clinical diagnostic accuracy of acute colonic diverticulitis in patients
admitted with acute abdominal pain. RESULTS: Of 833 patients admitted with acute
abdominal pain, 95 had acute colonic diverticulitis. ROC curve analysis gave an
area under the ROC curve (AUC) of 0.95 (CI 0.92 to 0.97) for ages <65 years, AUC
= 0.86 (CI 0.78 to 0.93) in older patients. Separate analysis showed an AUC =
0.83 (CI 0.80 to 0.86) of CRP alone. White blood cell count and temperature were
almost useless to discriminate acute colonic diverticulitis from other types of
acute abdominal pain, AUC = 0.59 (CI 0.53 to 0.65) for white blood cell count and
AUC = 0.57 (0.50 to 0.63) for temperature, respectively. CONCLUSION: This
prospective study demonstrates that standard clinical evaluation by non
specialist doctors based on history, physical examination, and initial blood
tests on admission provides a high degree of diagnostic precision in patients
with acute colonic diverticulitis.
PMID- 27613729
TI - Evaluation of the microbiome in children's appendicitis.
AB - BACKGROUND/AIM: The role of the microbiome has been widely discussed in the
etiology of appendicitis. The primary aim was to evaluate the microbiome in the
normal appendix and in appendicitis specifically divided into the three
clinically and histopathologically defined grades of inflammation. Secondary aims
were to examine whether there were any microbiome differences between proximal
and distal appendices, and relate the microbiome with histopathological findings.
METHODS: A prospective pilot study was conducted of children undergoing
appendectomy for appendicitis. The diagnosis was based on histopathological
analysis. Children with incidental appendectomy were used as controls. The
proximal and distal mucosa from the appendices were analyzed with 16S rRNA gene
sequencing. RESULTS: A total of 22 children, 3 controls and 19 appendicitis
patients; 11 phlegmonous, 4 gangrenous, and 4 perforated appendices, were
prospectively included. The amount of Fusobacterium increased and Bacteroides
decreased in phlegmonous and perforated appendicitis compared to controls, but
statistical significance was not reached, and this pattern was not seen in
gangrenous appendicitis. No relation could be seen between different bacteria and
the grade of inflammation, and there was a wide variation of abundances at
phylum, genus, and species level within every specific group of patients.
Further, no significant differences could be detected when comparing the
microbiome in proximal and distal mucosa, which may be because the study was
underpowered. A trend with more abundance of Fusobacteria in the distal mucosa
was seen in appendicitis patients with obstruction (25 and 13 %, respectively, p
= 0.06). CONCLUSION: The pattern of microbiome differed not only between groups,
but also within groups. However, no statistically significant differences could
be found in the microbiome between groups or clinical conditions. No correlation
between a specific bacteria and grade of inflammation was found. In the vast
majority of cases of appendicitis, changes in microbiome do not seem to be the
primary event. Since there seem to be differences in microbiome patterns
depending on the sample site, the exact localization of biopsy sampling must be
described in future studies.
PMID- 27613730
TI - Encapsulated Fat Necrosis Mimicking an Intra-abdominal Tumor.
AB - ?.
PMID- 27613731
TI - High-Density Free Fluid on Computed Tomography: a Predictor of Surgical
Intervention in Patients with Adhesive Small Bowel Obstruction.
AB - BACKGROUND: Patients with adhesive small bowel obstruction (ASBO) often develop
intraabdominal free fluid (IFF). While IFF is a finding on abdominopelvic
computed tomography (CT) associated with the need for surgical intervention, many
patients with IFF can be still managed non-operatively. A previous study
suggested that a higher red blood cell count of IFF is highly predictive of
strangulated ASBO. We hypothesized that radiodensity in IFF (Hounsfield unit
(HU)) on CT would predict the need for surgical intervention. STUDY DESIGN:
Patients with clinicoradiological evidence of ASBO between January 2009 and
December 2013 were identified. In patients with IFF > 3 cm2 identified on CT, the
HU was measured in the largest pocket of IFF. A sensitivity analysis was
performed to determine a high-density HU threshold. The HU of patients who
underwent therapeutic laparotomy was compared with those successfully discharged
with non-operative management. RESULTS: A total of 318 patients with ASBO (median
age 52 years, 56.0 % male) were identified. Of 111 patients who had IFF on CT,
55.9 % underwent therapeutic laparotomy and 15.3 % required bowel resection.
Radiodensity of IFF in the operative group was significantly higher than that in
the non-operative group (18.2 vs. 7.0 HU, p < 0.01). Sensitivity, specificity,
positive predictive value, negative predictive value, and accuracy of high
density IFF (>10 HU) to predict the need for surgical intervention were 83.9,
65.3, 75.4, 76.2, and 75.6 %, respectively. CONCLUSIONS: High-density IFF on CT
was significantly associated with the need for surgical intervention in patients
with ASBO. Prospective study to validate the predictive value of high-density IFF
on CT will be warranted.
PMID- 27613733
TI - Characterizing Readmissions After Bariatric Surgery.
AB - INTRODUCTION: Readmissions are an important quality metric for surgery. Here, we
compare characteristics of readmissions across laparoscopic Roux-en-Y gastric
bypass (LRYGB), sleeve gastrectomy (LSG), and adjustable gastric band (LAGB).
METHODS: Demographic, intraoperative, anthropometric, and laboratory data were
prospectively obtained for 1775 patients at a single academic institution. All
instances of readmissions within 1 year were recorded. Data were analyzed using
STATA, release 12. RESULTS: For the 1775 patients, 113 (6.37 %) were readmitted.
Mean time to readmission was 52.1 days. Of all the readmissions, 64.6 % were
within 30 days, 22.1 % from 30 to 90 days, 1.77 % from 90 to 180 days, and 11.5 %
from 180 to 365 days. Incidence of 30-day readmissions varied across surgeries
(LRYGB: 7.17 %; LAGB: 3.05 %; LSG: 4.25 %, p = 0.04). Time to readmission varied
as well, with 90.0 % of LSG and 80.0 % of LABG patients within the first 30 days,
versus 60.8 % of LRYGB (p = 0.02). The most common causes of readmissions were
gastrointestinal issues related to index procedure (34.5 %) and did not vary
across surgeries. In multivariable logistic regression, index hospital length of
stay (LOS) was associated with readmission (OR = 1.07, 95 % CI 1.02-1.13, p =
0.01). CONCLUSIONS: Readmissions after bariatric surgery are associated with high
index hospital LOS, and a measureable proportion of procedure-related
readmissions can occur up to 1 year, especially for LRYGB.
PMID- 27613732
TI - Factors Associated with Repeated Health Resource Utilization in Patients with
Diverticulitis.
AB - Conservative management trends in diverticulitis may lead to increased
hospitalizations secondary to repeated attacks. The study aimed to characterize
trends in management and risk-assess patients with diverticulitis that required
multiple admissions to identify high utilizers. A total of 265,724 patients with
diverticulitis were identified from 1995 to 2014 from the New York SPARCS
database. Patients with >=2 hospital admissions were stratified across
demographics, comorbidities, insurance status, and surgical intervention. In
total, 42,850 patients had >=2 hospital admissions. Risk factors for >=2
admissions included younger age, White race, obesity, hypertension, pulmonary
disease, hypothyroidism, rheumatoid arthritis, and depression. Fifty-two percent
of these patients went on to have surgery. The percentage of elective cases
increased from 59 to 70 %, while emergent cases conversely decreased from 41 to
30 %. One in five patients admitted with diverticulitis required two or more
admissions. Numerous patient factors were correlated with increased risk of
readmission. These factors may be used to guide treatment decisions and help
reduce economic burden in frequent utilizers. Trends in surgery rates for these
patients could reflect improved treatment options and/or changing clinical
practice patterns.
PMID- 27613734
TI - Giant Retroperitoneal Sarcoma.
AB - Retroperitoneal sarcomas are rare tumors, having an annual incidence of 0.3 to
0.4 new cases per 100,000 occupants. R0 resection is the cornerstone of therapy,
with local control being integral for a favorable prognosis. We present a case of
giant retroperitoneal liposarcoma treated with complete surgical resection.
PMID- 27613735
TI - National Trends in Postoperative Outcomes and Cost Comparing Minimally Invasive
Versus Open Liver and Pancreatic Surgery.
AB - BACKGROUND: Although minimally invasive surgery (MIS) has been associated with
improved postoperative clinical outcomes, the widespread use of MIS by procedure
and hospital has been limited. We sought to report on national trends
postoperative clinical outcomes for minimally invasive liver and pancreatic
surgery. METHODS: Patients undergoing an elective liver or pancreatic resection
were identified using the Nationwide Inpatient Sample between 2002 and 2012.
Multivariable regression analysis was used to compare postoperative outcomes, and
total hospital costs between patients who underwent a MIS versus an open
resection over the study time period. RESULTS: A total of 47,685 patients were
identified; 21,280 (44.6 %) patients underwent a hepatic resection while
26,405(55.4 %) patients underwent a pancreatic resection. MIS was performed in
2674 (5.6 %) patients and increased from 2.6 % in 2002 to 9.6 % in 2012 (p <
0.001); this trend was observed for both pancreatic and liver resections (both p
< 0.001). Over the study time period, use of MIS was consistently associated with
improved postoperative outcomes including decreased postoperative morbidity (open
vs. MIS: 32.9 vs. 29.6 %) and a shorter length-of-stay (<=4 days; MIS, 21.4 %;
Open, 13.7 %; both p < 0.05). The median costs associated with MIS decreased over
time compared with the open surgical approach and were on average $572 lower than
the cost associated with open surgery. CONCLUSION: Compared to open resection,
MIS was associated with lower postoperative morbidity, a shorter length-of-stay,
and lower cost. The use of MIS should be encouraged in order to improve
postoperative outcomes and decrease healthcare spending via value enhancement.
PMID- 27613736
TI - Comparison of restriction enzyme pattern analysis and full gene sequencing of 16S
rRNA gene for Nocardia species identification, the first report of Nocardia
transvalensis isolated of sputum from Iran, and review of the literature.
AB - Nocardial infections occur in different organs of the body and are common in
immune disorder diseases of individuals. The aim of this study was to assess
Nocardia species identification by phenotypic tests and molecular techniques
applied to nocardiosis in Iranian patients. In the current study, various
clinical samples were collected and cultured on conventional media and using the
paraffin baiting method. Various phenotypic tests were performed. For accurate
identification at the species level, restriction fragment length polymorphisms
(RFLP) in the hsp65 and partial 16S rRNA genes and full gene sequencing of the
16S rRNA gene were used. Twenty-seven Nocardia spp. were isolated and analysis of
phenotypic tests results showed Nocardia asteroides complex, Nocardia
otitidiscaviarum, Nocardia nova, and Nocardia spp. New RFLP patterns of Nocardia
strains with hsp65 and partial 16S rRNA genes were obtained. Full gene sequencing
of the 16S rRNA gene identified Nocardia cyriacigeorgica, N. otitidiscaviarum,
Nocardia farcinica, Nocardia transvalensis, and N. nova. Nocardia infections are
rarely reported and this genus is the cause of various illnesses. Accurate
identification of Nocardia spp. is important for epidemiology studies and
treatment. It should also be noted that some species may have similar RFLP
patterns; therefore, full gene sequencing of the 16S rRNA gene is necessary for
confirmation.
PMID- 27613737
TI - The Effects of Nutrition Awareness and Knowledge on Health Habits and Performance
Among Pharmacy Students in Egypt.
AB - A cross-sectional study was conducted on a group of pharmacy students to assess
the relation between nutritional knowledge and awareness of university students
and their nutrition habits and health related performance and indicators. The
students were subjected to a questionnaire designed to approach four health
related topics including nutrition literacy, health awareness, nutritional habits
and health related performance. Answers on each topic were collected and
statistical analysis was performed using GraphPad Prism 5 software including a
measure of gender differences and correlative studies. No significant difference
between genders in the overall responses but discrepancies in certain questions
were observed. Female students showed higher awareness of nutrition concepts and
practices but poor implementation from their side was observed. The study
revealed that a positive and significant correlation existed between health
related performance and nutrition literacy (r = 0.32). Healthier eating habits
and lifestyle were associated more with nutrition conscious students (r = 0.73)
than knowledgeable students (r = 0.56). It was concluded that knowledge alone is
not enough to stimulate individuals to practice healthy habits. Other
implementations are required to raise awareness of the issues at hand.
PMID- 27613738
TI - Prevalence and Determinants of Repeat Mammography Among Women from a Developing
Country.
AB - Failures in repeat mammography decrease the potential benefits of screening;
however, it is notable that the recent use of mammography is more frequently
studied than repeat use. We estimated the prevalence and analyzed determinants
for repeat mammography among women from Mexico, a developing country of Latin
America. It was a two-stage study with an initial cross-sectional design (n =
1045) and a final case-control design that involved women of at least 45 years of
age with no history of breast, ovarian, or uterine cancer. Case subjects were
those with three or more mammograms in the last 5 years, with the last one
carried out within the last two years (n = 444); control subjects included those
who underwent >=3 mammograms throughout their life with the most recent carried
out >2 years ago (n = 444). Through interviews, we evaluated context-dependency,
fulfillment of expected outcomes, self-efficacy, and risk perception, among other
factors. We estimated the prevalence with 95 % confidence intervals (CI), and
odds ratios (OR) using multivariate binary logistic regression. The prevalence of
repeat mammography was 40.4 % (95 % CI 37.4-43.4). Self-efficacy demonstrated the
highest effect on repeat use (OR 7.7, 95 % CI 4.7-12.6), followed by awareness
context-dependency (OR 4.9, 95 % CI 3.3-7.2), the use of Papanicolaou testing (OR
3.5, 95 % CI 2.3-5.2), the fulfillment of expected waiting time outcome (OR 2.4,
95 % CI 1.2-4.7), and context-dependency related to self-referral/health provider
referral (OR 2.4, 95 % CI 1.7-3.4), independent of risk perception, age,
education, and positive emotional state of mind. The study showed a need for
increasing the prevalence of promoting awareness of the determining factors of
repeat mammography, which is a necessary component in the early detection of
breast cancer.
PMID- 27613739
TI - Time-to-Treatment for Myocardial Infarction: Barriers and Facilitators Perceived
by American Indians in Three Regions.
AB - Early recognition of acute myocardial infarction (MI), followed by prompt
emergency care, improves patient outcomes. Among rural American Indian (AI)
populations there are disparities in access to care for MI and processes of care,
resulting in poor MI-related health outcomes compared to the general population.
We sought to gain an understanding of barriers related to MI time-to-treatment
delays using a qualitative approach. We conducted semi-structured interviews and
focus groups with AI key informants and community members in three Indian Health
Service regions. Major barriers to care included long travel distance to care and
lack of supporting infrastructure; distrust of the health care system; low
overall literacy and basic health literacy; priority of family care-giving; and
lack of specialized medical facilities and specialists. Findings suggest that
improved time-to-treatment facilitators include educating the local community
about the causes and consequences of MI and culturally-sensitive health
communication, as well as addressing the quality of local systems of care and the
community's perception of these systems. Pursuing these strategies may improve
quality of care and reduce MI-related morbidity and mortality in rural AI
populations.
PMID- 27613741
TI - US Federal Trade Commission charges academic publisher over "deceptive"
practices.
PMID- 27613740
TI - Child Passenger Safety in the Somali Communities of Columbus, Ohio.
AB - Children (particularly low-income minorities and refugees) are at high risk for
serious injury or death from motor vehicle crashes. Interpreter-assisted data
collection included key informant interviews, focus groups and face-to-face
surveys with the Somali community of Columbus, Ohio about child passenger safety.
Measurements included prevalence of child safety seats use, awareness and
knowledge of and barriers to proper use in order to inform development,
implementation, and initial evaluation of a culturally-appropriate intervention
for Somali families. Somali parents regarded child passenger safety as an
important topic, but many reported improper restraint behaviors of one or more
children and/or did not have an adequate number of child safety seats. Few
parents reported having child safety seats installed by a professional
technician. Child passenger safety practices in the Somali communities of
Columbus are a public health concern that should be addressed with culturally
appropriate interventions.
PMID- 27613742
TI - OAG-Abstractsband zur OAG-Jahrestagung 2016.
PMID- 27613743
TI - Seeing number using texture: How summary statistics account for reductions in
perceived numerosity in the visual periphery.
AB - Peripheral visual perception is characterized by reduced information about
appearance due to constraints on how image structure is represented. Visual
crowding is a consequence of excessive integration in the visual periphery. Basic
phenomenology of visual crowding and other tasks have been successfully accounted
for by a summary-statistic model of pooling, suggesting that texture-like
processing is useful for how information is reduced in peripheral vision. I
attempt to extend the scope of this model by examining a property of peripheral
vision: reduced perceived numerosity in the periphery. I demonstrate that a
summary-statistic model of peripheral appearance accounts for reduced numerosity
in peripherally viewed arrays of randomly placed dots, but does not account for
observed effects of dot clustering within such arrays. The model thus offers a
limited account of how numerosity is perceived in the visual periphery. I also
demonstrate that the model predicts that numerosity estimation is sensitive to
element shape, which represents a novel prediction regarding the phenomenology of
peripheral numerosity perception. Finally, I discuss ways to extend the model to
a broader range of behavior and the potential for using the model to make further
predictions about how number is perceived in untested scenarios in peripheral
vision.
PMID- 27613745
TI - Patient Dose in Fluoroscopically Guided Cervical Discectomy and Fusion.
AB - Cervical discectomy and fusion (CDF) is a minimally invasive procedure, where the
accurate placement of the implants is accomplished using fluoroscopic guidance.
Therefore, the evaluation of the radiation dose becomes mandatory. The purpose of
the current study was to assess patient dose during fluoroscopically guided
anterior and/or posterior CDF procedures. Thirty-three patients undergoing single
or multiple-level CDF were studied using a mobile C-arm system. Data regarding
fluoroscopy time (FT), air kerma area product (KAP) and cumulative dose (CD) were
recorded. Patient entrance surface dose (ESD), thyroid absorbed dose and
effective dose (ED) were calculated from KAP measurements, utilizing the CALDoseX
software. The average FT was 0.12 min (range 0.02-0.48 min), resulting to a KAP
value of 0.21 Gy cm2 (range 0.01-1.46 Gy cm2) and a CD value of 0.96 mGy (range
0.04-6.58 mGy). The ESD ranged between 0.08 and 13.58 mGy (average 1.95 mGy), the
ED between 0.001 and 0.097 mSv (average 0.015 mSv), while the dose absorbed by
the thyroid ranged between 0.01 and 1.12 mGy (average 0.194 mGy). The dose
associated with the CDF procedure is very low, comparable to that delivered by a
lateral X-ray radiograph of the cervical spine. However, higher doses can be
revealed, due to the non-optimum use of the X-ray system and extended FTs, mainly
affected by complex clinical conditions, as well as the experience of the
neurosurgeon. Additional studies need to be conducted for further investigation
of the patient dose from the CDF procedure.
PMID- 27613746
TI - Monte Carlo Simulation of Radiotherapy for Breast Cancer in Pregnant Patients:
How to Reduce the Radiation Dose and Risks to Fetus?
AB - This study estimated the fetal dose and risks from radiotherapy for breast cancer
with 6 MV X-rays. Breast irradiation was simulated with the MCNP code using two
mathematical phantoms corresponding to patients in the early and middle periods
of pregnancy. Monte Carlo simulations were performed to determine the appropriate
fetal shielding. For a 50-Gy tumor dose, the unshielded fetal dose reached up to
133.1 mGy. Fetal protection with a lead shield of dimensions 30 * 30 * 5 cm3
placed besides the treatment couch resulted in maximum doses of 22.0 and 70.3 mGy
at the first and second trimesters of gestation, respectively. These shielded
fetal doses may be associated with a fatal cancer risk during childhood up to
0.42% and a maximum probability for the appearance of heritable effects of 0.17%.
The use of fetal shielding ensures the absence of deterministic effects from
radiotherapy during the first 24 weeks of gestation.
PMID- 27613744
TI - Why Is Apolipoprotein CIII Emerging as a Novel Therapeutic Target to Reduce the
Burden of Cardiovascular Disease?
AB - ApoC-III was discovered almost 50 years ago, but for many years, it did not
attract much attention. However, as epidemiological and Mendelian randomization
studies have associated apoC-III with low levels of triglycerides and decreased
incidence of cardiovascular disease (CVD), it has emerged as a novel and
potentially powerful therapeutic approach to managing dyslipidemia and CVD risk.
The atherogenicity of apoC-III has been attributed to both direct lipoprotein
lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion
of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in
vascular cells and impairing LPL-independent hepatic clearance of TRL remnants.
Encouraging results from clinical trials using antisense oligonucleotide, which
selectively inhibits apoC-III, indicate that modulating apoC-III may be a potent
therapeutic approach to managing dyslipidemia and cardiovascular disease risk.
PMID- 27613747
TI - Software Development for Estimating the Conversion Factor (K-Factor) at Suitable
Scan Areas, Relating the Dose Length Product to the Effective Dose.
AB - We developed a k-factor-creator software (kFC) that provides the k-factor for CT
examination in an arbitrary scan area. It provides the k-factor from the
effective dose and dose-length product by Imaging Performance Assessment of CT
scanners and CT-EXPO. To assess the reliability, we compared the kFC-evaluated k
factors with those of the International Commission on Radiological Protection
(ICRP) publication 102. To confirm the utility, the effective dose determined by
coronary computed tomographic angiography (CCTA) was evaluated by a phantom study
and k-factor studies. In the CCTA, the effective doses were 5.28 mSv in the
phantom study, 2.57 mSv (51%) in the k-factor of ICRP, and 5.26 mSv (1%) in the k
factor of the kFC. Effective doses can be determined from the kFC-evaluated k
factors in suitable scan areas. Therefore, we speculate that the flexible k
factor is useful in clinical practice, because CT examinations are performed in
various scan regions.
PMID- 27613748
TI - Answers to if the Lead Aprons are Really Helpful in Nuclear Medicine from the
Perspective of Spectroscopy.
AB - Wearing lead X-ray-protective aprons is a routine in nuclear medicine department
in parts of China. However, the staff are often perplexed by questions such as if
it is imperative to wear aprons when injecting radioactive drugs, how much
radiation dosage can be shielded and if the apron will produce secondary
radiation instead? To answer these questions, a semiconductor detector was
employed to record different gamma and X-ray spectra with and without the lead
apron or lead sheet. Then, we could estimate the signal shielding ratio to
different photons for the lead apron and compare with the hospitals measured
data. In general, the two results coincided well. The spectral results showed
that the detrimental secondary X-rays irradiation rises when the energy of gamma
rays exceeds the K absorption edge of lead (88 keV). Moreover, the aprons are not
so effective for gamma rays of 364 keV emitted from 131I and 511 keV emitted from
the positron radioactive nuclides. This work is purely a physical measurement in
the laboratory. To the best of our knowledge, this is the first quantitative
study on the level of gamma rays protection offered by the medical lead aprons
and the importance of the spectroscopic measurements is discussed in this paper.
PMID- 27613749
TI - The Mayak Worker Dosimetry System (MWDS-2013): Plutonium Binding in the Lungs-An
Analysis of Mayak Workers.
AB - Estimates of plutonium lung doses from urine bioassay are highly dependent on the
rate of absorption from the lungs to blood assumed for the inhaled aerosol.
Absorption occurs by dissolution of particles in lung fluid followed by uptake to
blood. The latter may occur either rapidly or dissolved ions may first become
temporarily bound within airway tissue. The presence of long-term binding can
greatly increase lung doses, particularly if it occurs in the bronchial and
bronchiolar regions. Analyses of autopsy data from Beagle dogs and USTUR Case
0269, obtained following exposure to plutonium nitrate, suggest that a small
fraction of 0.2-1.1 and 0.4-0.7%, respectively, of plutonium becomes permanently
bound within the lungs. The present work performs a further analysis using
autopsy data of former plutonium workers of the Mayak Production Association to
determine values of the bound fraction that are supported by these data. The
results suggest a bound fraction value of 0-0.3%. The results also indicate that
the Mayak worker population median values of the particle transport clearance
parameters from the alveolar-interstitial region are largely consistent with
expected values, but suggest the rate from the alveolar region to the
interstitium may be lower than initially thought.
PMID- 27613750
TI - Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in
Physcomitrella patens.
AB - Powerful genome editing technologies are needed for efficient gene function
analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out
technology in a variety of species. However, in a number of situations, knocking
out or modifying a single gene is not sufficient; this is particularly true for
genes belonging to a common family, or for genes showing redundant functions.
Like many plants, the model organism Physcomitrella patens has experienced
multiple events of polyploidization during evolution that has resulted in a
number of families of duplicated genes. Here, we report a robust CRISPR-Cas9
system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA
vectors, and a cassette for transient transformation selection, for gene knock
out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting
of five different genes allows the selection of a quintuple mutant, and all
possible subcombinations of mutants, in one experiment, with no mutations
detected in potential off-target sequences. Furthermore, we confirmed the
observation that the presence of repeats in the vicinity of the cutting region
favors deletion due to the alternative end joining pathway, for which induced
frameshift mutations can be potentially predicted. Because the number of multiple
gene families in Physcomitrella is substantial, this tool opens new perspectives
to study the role of expanded gene families in the colonization of land by
plants.
PMID- 27613751
TI - The Genetic Basis of Upland/Lowland Ecotype Divergence in Switchgrass (Panicum
virgatum).
AB - The evolution of locally adapted ecotypes is a common phenomenon that generates
diversity within plant species. However, we know surprisingly little about the
genetic mechanisms underlying the locally adapted traits involved in ecotype
formation. The genetic architecture underlying locally adapted traits dictates
how an organism will respond to environmental selection pressures, and has major
implications for evolutionary ecology, conservation, and crop breeding. To
understand the genetic architecture underlying the divergence of switchgrass
(Panicum virgatum) ecotypes, we constructed a genetic mapping population through
a four-way outbred cross between two northern upland and two southern lowland
accessions. Trait segregation in this mapping population was largely consistent
with multiple independent loci controlling the suite of traits that characterizes
ecotype divergence. We assembled a joint linkage map using ddRADseq, and mapped
quantitative trait loci (QTL) for traits that are divergent between ecotypes,
including flowering time, plant size, physiological processes, and disease
resistance. Overall, we found that most QTL had small to intermediate effects.
While we identified colocalizing QTL for multiple traits, we did not find any
large-effect QTL that clearly controlled multiple traits through pleiotropy or
tight physical linkage. These results indicate that ecologically important traits
in switchgrass have a complex genetic basis, and that similar loci may underlie
divergence across the geographic range of the ecotypes.
PMID- 27613752
TI - Suitability of Different Mapping Algorithms for Genome-Wide Polymorphism Scans
with Pool-Seq Data.
AB - The cost-effectiveness of sequencing pools of individuals (Pool-Seq) provides the
basis for the popularity and widespread use of this method for many research
questions, ranging from unraveling the genetic basis of complex traits, to the
clonal evolution of cancer cells. Because the accuracy of Pool-Seq could be
affected by many potential sources of error, several studies have determined, for
example, the influence of sequencing technology, the library preparation
protocol, and mapping parameters. Nevertheless, the impact of the mapping tools
has not yet been evaluated. Using simulated and real Pool-Seq data, we
demonstrate a substantial impact of the mapping tools, leading to characteristic
false positives in genome-wide scans. The problem of false positives was
particularly pronounced when data with different read lengths and insert sizes
were compared. Out of 14 evaluated algorithms novoalign, bwa mem and clc4 are
most suitable for mapping Pool-Seq data. Nevertheless, no single algorithm is
sufficient for avoiding all false positives. We show that the intersection of the
results of two mapping algorithms provides a simple, yet effective, strategy to
eliminate false positives. We propose that the implementation of a consistent
Pool-Seq bioinformatics pipeline, building on the recommendations of this study,
can substantially increase the reliability of Pool-Seq results, in particular
when libraries generated with different protocols are being compared.
PMID- 27613753
TI - A practical approach to Events Medicine provision.
AB - In the past three decades, mass casualty incidents have occurred worldwide at
multiple sporting events and other mass gatherings. Organisational safety and
healthcare provision can consequently be scrutinised post-event. Within the UK,
such incidents in the 1980s provided incentives to improve medical services and
subsequent high profile UK-based international sporting events (London Olympics
and Paralympics 2012, Glasgow Commonwealth Games 2014, Rugby World Cup 2015)
added a further catalyst for developing services. Furthermore in the aftermath of
the abandoned France versus Germany association football match at the Stade de
France (Paris Terrorist Attacks, November 2015) and the 2016 UK report from HM
Coroner on the Hillsborough Inquest, medical cover at sporting events is being
further reviewed. Doctors providing spectator cover therefore need to have an
awareness of their likely roles at sporting venues. Formal guidance exists in
many countries for the provision of such cover but remains generic even though
Events Medicine is increasingly recognised as a necessary service. The current
evidence base is limited with best practice examples often anecdotally cited by
acute care specialists (eg, emergency medicine) who provide cover. This article
is therefore intended to present an overview for doctors of the knowledge and
skills required to treat ill and injured spectators and enable them to adequately
risk-assess venues in cooperation with other health and safety providers,
including preparation for a major incident. It also gives guidance on how
activity can be adequately assessed and how doctors can have management roles in
Events Medicine.
PMID- 27613756
TI - Ideological Differences in Anchoring and Adjustment During Social Inferences.
AB - Recent research has demonstrated that conservatives perceive greater similarity
to political ingroup members than do liberals. In two studies, we draw from a
framework of "anchoring and adjustment" to understand why liberals and
conservatives differ in their perceptions of ingroup similarity. Results indicate
that when participants made judgments under time pressure, liberals and
conservatives did not differ in assuming ingroup similarity. However, when
participants were given sufficient time to make judgments, liberals assumed less
similarity than conservatives did, suggesting that liberals adjusted their
judgments to a greater extent than conservatives did (Studies 1 and 2). In
examining an underlying motivational process, we found that when conservatives'
desire to affiliate with others was attenuated, they adjusted their initial
judgments of ingroup similarity to a similar extent as liberals did (Study 2). We
discuss implications for research on ideology and social judgment.
PMID- 27613754
TI - Diagnostic accuracy of the APPY1 Test in patients aged 2-20 years with suspected
acute appendicitis presenting to emergency departments.
AB - OBJECTIVE: Evaluate the diagnostic accuracy of the APPY1 Test alone and in
combination with the Alvarado score (AS) to rule out acute appendicitis (AA) in
patients presenting to EDs with abdominal pain suspicious for AA. METHODOLOGY:
Observational study in a prospective consecutive cohort including all patients
from 2 to 20 years with abdominal pain suggestive of AA in four EDs. The APPY1
Test was performed and AS was calculated to determine risk stratification for
each patient. RESULTS: 321 patients enrolled (mean age 11.8 (SD 3.8) years, 52.0%
male), with 32.4% low risk, 23.7% intermediate risk and 43.9% high risk according
to the AS. 111 (34.6%) had AA, of whom 1 (0.9%) had a false-negative APPY1 Test
result. The APPY1 Test had a sensitivity (Se) of 99.1% (95% CI 94.4% to 99.9%),
specificity (Sp) of 32.9% (95% CI 26.6% to 39.7%), negative predictive value
(NPV) of 98.6% (95% CI 91.2% to 99.9%) and negative likelihood ratio (LHR-) of
0.03 (0.00 to 0.19) in this population. For patients at low risk by AS, the APPY1
Test had a Se of 100% (95% CI 62.9% to 100%), NPV of 100% (95% CI 91.1% to 100%)
and LHR- of 0.0 (not calculable), and for patients at intermediate risk by AS,
the APPY1 Test had a Se of 94.4% (95% CI 70.6% to 99.7%), NPV of 94.7% (95% CI
71.9% to 99.7%) and LHR- of 0.18 (0.0 to 1.2), respectively. CONCLUSIONS: APPY1
Test is a potentially useful diagnostic tool to rule out AA in this population,
with clinical utility primarily in those patients classified as having low
clinical risk of appendicitis according to the AS.
PMID- 27613755
TI - Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese
steelworks firm sample.
AB - OBJECTIVES: Noise-induced hearing loss is one of the most serious occupational
diseases worldwide. It is caused by interactions between environmental and
genetic factors. The purpose of this study was to examine the association between
the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk
of developing noise-induced hearing loss in China. METHODS: A case-control
association study was carried out with 326 hearing loss cases and 326 controls
matched with age and duration of noise exposure, drawn from a cohort of steel
workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected
and genotyped. Logistic regression was performed to analyse the main effect of
genotypes and interactions between genotypes and individual/environmental factors
adjusted for confounding factors. Moreover, generalised multiple dimensionality
reduction was applied to further detect interaction among the 5 selected SNPs.
RESULTS: Analysis revealed that locus polymorphism of rs3813346 was associated
with the risk of developing noise-induced hearing loss in the dominance model,
the codominance model and the addictive model (p=0.004, 0.009 and 0.003,
respectively). A significant interaction between rs9321402 and cumulative noise
exposure was found (p=0.002). A significant main effect p value (p=0.006) was
obtained in the high-level exposure group (cumulative noise exposure >=98 dB(A)).
Generalised multiple dimensionality reduction indicated that the combined
interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the
incidence of noise-induced hearing loss. CONCLUSIONS: The research suggests that
EYA4 genetic variant and its interaction with noise levels may modify the
susceptibility to develop noise-induced hearing loss in Chinese population.
PMID- 27613757
TI - Drug deaths hit record high in England and Wales, figures show.
PMID- 27613759
TI - Nail Scabies: An Unusual Presentation Often Overlooked and Mistreated.
AB - Nail scabies is an interesting clinical presentation of scabies. Although it is
usually found concomitant with characteristic dermatologic manifestations, it may
present as an isolated finding in the immunocompromised host. This condition is
commonly mistaken with other diseases such as nail dystrophy, nail psoriasis and
onychomycosis. We report two cases of unusual nail presentations that provide
clues to diagnosis. Also, literature on unusual nail and dermatologic
presentations was reviewed to recognize dermatologist consideration for
appropriate treatment options.
PMID- 27613758
TI - Renin-angiotensin system gene expression and neurodegenerative diseases.
AB - HYPOTHESIS: Single nucleotide polymorphisms and altered gene expression of
components of the renin-angiotensin system (RAS) are associated with
neurodegenerative diseases. INTRODUCTION: Drugs that interact with the RAS have
been shown to affect the course of neurodegenerative disease, suggesting that
abnormalities in the RAS may contribute to neurodegenerative disease. MATERIALS
AND METHODS: A meta-analysis of genome-wide association studies and gene
expression data for 14 RAS-related proteins was carried out for five
neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy,
amyotrophic lateral sclerosis and multiple sclerosis. RESULTS: No single
nucleotide polymorphisms in any of the 14 RAS-related protein genes were
significantly associated with the five neurodegenerative diseases investigated.
There was an inverse association between expression of ATP6AP2, which encodes the
(pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's
disease. An association of AGTR, which encodes the AT1 angiotensin II receptor,
and Parkinson's disease and Alzheimer's disease was also observed. CONCLUSIONS:
To date, no single nucleotide polymorphisms in components of the RAS can be
definitively linked to the neurodegenerative diseases evaluated in this study.
However, altered gene expression of several components of the RAS is associated
with several neurodegenerative diseases, which may indicate that the RAS
contributes to the pathology of these diseases.
PMID- 27613760
TI - Morphology and Anatomic Patellar Instability Risk Factors in First-Time Traumatic
Lateral Patellar Dislocations: A Prospective Magnetic Resonance Imaging Study in
Skeletally Immature Children.
AB - BACKGROUND: The incidence of primary lateral patellar dislocation (LPD) in
children aged 9 to 14 years is 0.6 to 1.2 per 1000. Causation is assumed to be
multifactorial, including anatomic variants of the patellofemoral (PF) joint that
result in a higher risk of LPD. No publication has compared the morphology of the
PF joint and anatomic patellar instability risk factors (APIFs) in a primary LPD
population versus controls, defining children by skeletal maturity. PURPOSE: To
characterize the PF morphology and APIFs (trochlear dysplasia, abnormal lateral
patellar tilt, elevated tibial tubercle-trochlear groove [TT-TG] distance,
patella alta) through magnetic resonance imaging (MRI) measurements in skeletally
immature children with and without a primary LPD and to identify (potential)
distinctive differences between these 2 groups. STUDY DESIGN: Cross-sectional
study; Level of evidence, 3. METHODS: A prospective series of 103 skeletally
immature children aged 9 to 14 years with an MRI-confirmed primary LPD were
matched with a control group of 69 children. The PF morphology and APIFs were
assessed during a 2.5-year period with standardized MRI using sagittal and axial
views. RESULTS: In the LPD group, 79% had 2 to 4 APIFs compared with 7% in the
control group. All major measurements of trochlear dysplasia were significantly
different between the 2 groups. The mean central condylar height was
significantly higher in the LPD group compared with the control group, resulting
in a lower trochlear depth (2.3 vs 4.5 mm, respectively) and higher sulcus angle
(156.7 degrees vs 141.1 degrees , respectively). The LPD group had significantly
higher values of patellar height, Caton-Deschamps index (1.33 vs 1.15,
respectively), lateral patellar tilt (21.1 degrees vs 8.5 degrees ,
respectively), and TT-TG distance (13.9 vs 9.8 mm, respectively) compared with
the control group. The main divergent APIF was trochlear dysplasia (defined as
trochlear depth <3 mm), seen in 74% of the LPD group compared with 4% of the
control group. Elevated TT-TG distance as a single APIF was never present in the
LPD group; patellar tilt was only seen in the LPD group. The most common APIF in
the control group was patella alta (36%). CONCLUSION: There was a significant
difference in mean values of all established APIFs between the children with a
first-time LPD and the controls. Trochlear dysplasia was the main APIF, and
together with lateral patellar tilt (>=20 degrees ), they had the strongest
association with LPD.
PMID- 27613761
TI - Cell Viability in Arthroscopic Versus Open Autologous Chondrocyte Implantation.
AB - BACKGROUND: Autologous chondrocyte implantation (ACI) is an effective method of
repair of articular cartilage defects. It is a 2-stage operation, with the second
stage most commonly performed via mini-arthrotomy. Arthroscopic ACI is gaining
popularity, as it is less invasive and may accelerate early rehabilitation.
However, handling and manipulation of the implant have been shown to cause
chondrocyte cell death. PURPOSE: To assess the number and viability of cells
delivered via an open versus arthroscopic approach in ACI surgery. STUDY DESIGN:
Controlled laboratory study. METHODS: Sixteen ACI surgeries were performed on
young cadaveric knees by 2 experienced surgeons: 8 via mini-arthrotomy and 8
arthroscopically. Live and dead cells were stained and counted on implants after
surgery. The cell number and viability were assessed using confocal laser
scanning microscopy. Surgery was timed from knife to skin until the end of
cycling the knee 10 times after implantation of the cell-membrane construct.
RESULTS: On receipt of cell membranes after transportation from the laboratory,
>=92% of the cells were viable. There were significantly more remaining cells
(8.47E+07 arthroscopic vs 1.41E+08 open; P < .001) and 16 times more viable cells
(3.62% arthroscopic vs 37.34% open; P < .001) on the implants when they were
inserted via mini-open surgery compared with the arthroscopic technique. Open
surgery was of a significantly shorter duration (6 vs 32 minutes; P < .001).
CONCLUSION: In this study, there were significantly more viable cells on the
implant when ACI was performed via mini-arthrotomy compared with an arthroscopic
technique. CLINICAL RELEVANCE: The viability of cells delivered for ACI via an
arthroscopic approach was 16 times less than via an open approach. The mini
arthrotomy approach is recommended until long-term clinical comparative data are
available.
PMID- 27613762
TI - Surgical Release of the Pectoralis Minor Tendon for Scapular Dyskinesia and
Shoulder Pain.
AB - BACKGROUND: Pectoralis minor (PM) tightness has been linked to pain and
dysfunction of the shoulder joint secondary to anterior tilt and internal
rotation of the scapula, thus causing secondary impingement of the subacromial
space. PURPOSE: To describe outcomes pertaining to nonoperative and operative
treatment via surgical release of the PM tendon for pathologic PM tightness in an
active population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Over
a 3-year period, a total of 46 patients were enrolled (mean age, 25.5 years;
range, 18-33 years). Inclusion criteria consisted of symptomatic shoulder pain,
limited range of overhead motion, inability to participate in overhead lifting
activities, and examination findings consistent with scapular dysfunction
secondary to a tight PM with tenderness to palpation of the PM tendon. All
patients underwent a lengthy physical therapy and stretching program (mean, 11.4
months; range, 3-23 months), which was followed by serial examinations for
resolution of symptoms and scapular tilt. Of the 46 patients, 6 (13%) were unable
to adequately stretch the PM and underwent isolated mini-open PM release.
Outcomes were assessed with scapula protraction measurements and pain scales as
well as American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric
Evaluation (SANE), and visual analog scale (VAS) scores. RESULTS: Forty of the 46
patients (87%) resolved the tight PM and scapular-mediated symptoms with a
dedicated therapy program (pre- and posttreatment mean outcome scores: 58 and 91
[ASES], 50 and 90 [SANE], 4.9 and 0.8 [VAS]; P < .01 for all), but 6 patients
were considered nonresponders (mean score, 48 [ASES], 40 [SANE], 5.9 [VAS]) and
elected to have surgical PM release, with improved scores in all domains (mean
score, 89 [ASES], 90.4 [SANE], 0.9 [VAS]; P < .01) at final follow-up of 26
months (range, 25-30 months). Additionally, protraction of the scapula improved
from 1.2 to 0.3 cm in a mean midline measurement from the chest wall
preoperatively to postoperatively ( P < .01), similar to results in nonoperative
responders. No surgical complications were reported, and all patients returned to
full activities. CONCLUSION: In most patients, PM tightness can be successfully
treated with a nonoperative focused PM stretching program. However, in refractory
and pathologically tight PM cases, this series demonstrates predictable return to
function with notable improvement in shoulder symptoms after surgical release of
the PM. Additional research is necessary to evaluate the long-term efficacy of
isolated PM treatment.
PMID- 27613763
TI - Air pollution, deprivation and health: understanding relationships to add value
to local air quality management policy and practice in Wales, UK.
AB - Background: Air pollution exposure reduces life expectancy. Air pollution,
deprivation and poor-health status combinations can create increased and
disproportionate disease burdens. Problems and solutions are rarely considered in
a broad public health context, but doing so can add value to air quality
management efforts by reducing air pollution risks, impacts and inequalities.
Methods: An ecological study assessed small-area associations between air
pollution (nitrogen dioxide and particulate matter), deprivation status and
health outcomes in Wales, UK. Results: Air pollution concentrations were highest
in 'most' deprived areas. When considered separately, deprivation-health
associations were stronger than air pollution-health associations. Considered
simultaneously, air pollution added to deprivation-health associations;
interactions between air pollution and deprivation modified and strengthened
associations with all-cause and respiratory disease mortality, especially in
'most' deprived areas where most-vulnerable people lived and where health needs
were greatest. Conclusion: There is a need to reduce air pollution-related risks
for all. However, it is also the case that greater health gains can result from
considering local air pollution problems and solutions in the context of wider
health-determinants and acting on a better understanding of relationships.
Informed and co-ordinated air pollution mitigation and public health action in
high deprivation and pollution areas can reduce risks and inequalities. To
achieve this, greater public health integration and collaboration in local air
quality management policy and practice is needed.
PMID- 27613764
TI - Dose-response effect of smoking status on quality-adjusted life years among U.S.
adults aged 65 years and older.
AB - Background: To estimate the impact of smoking on quality-adjusted life years
(QALY) for US adults aged 65 years and older. Methods: Using the 2003-08 National
Health and Nutrition Examination Survey Linked Mortality File, we estimated the
mean QALY throughout the remaining lifetime by participants' smoking status as
well as smoking intensity and time since cessation. Results: Never, former and
current smokers had a mean QALY of 16.1, 12.7 and 7.3 years, respectively. Among
current smokers, those who started smoking before age 18 had fewer QALYs than
those who started at or after age 18 (6.0 and 8.5 years, respectively) and those
smoking >=20 cigarettes per day had fewer QALYs than those smoking <20 cigarettes
per day (6.6 and 8.1 years, respectively). QALYs also declined with a longer
duration of smoking and a shorter time since cessation. The potential gains if a
person quit smoking would be 5.4 QALYs, and the gains would increase with a
longer time since quitting as well as quitting at a younger age. Conclusions:
This study demonstrated the dose-response effect of smoking status on QALY. The
results indicate the health benefits of tobacco cessation at any age and sizeable
losses for former or current smokers.
PMID- 27613765
TI - Sampling frame for sexual minorities in public health research.
PMID- 27613766
TI - Mental health inequalities among gay and bisexual men in England, Scotland and
Wales: a large community-based cross-sectional survey.
PMID- 27613767
TI - Cost-effectiveness analysis of eliminating industrial and all trans fats in
England and Wales: modelling study.
AB - Introduction: Coronary heart disease (CHD) remains a leading cause of UK
mortality. Dietary trans fats (TFA) represent a powerful CHD risk factor.
However, UK efforts to reduce intake have been less successful than other
nations. We modelled the potential health and economic effects of eliminating
industrial and all TFA up to 2020. Methods: We extended the previously validated
IMPACTsec model, to estimate the potential effects on health and economic
outcomes of mandatory reformulation or a complete ban on dietary TFA in England
and Wales from 2011 to 2020. We modelled two policy scenarios: 1) Elimination of
industrial TFA consumption, from 0.8% to 0.4% daily energy 2) Elimination of all
TFA consumption, from 0.8% to 0. Results: Elimination of industrial TFA across
the England and Wales population could result in approximately 1600 fewer deaths
per year, with some 4000 fewer hospital admissions; gaining approximately 14 000
additional life years. Health inequalities would be substantially reduced in both
scenarios. Elimination of industrial TFA would be cost saving. This would include
approximately L100 m saved in direct healthcare costs. Elimination of all TFA
would double the health and economic gains. Conclusions: Eliminating industrial
or all UK dietary intake of TFA could substantially reduce CHD mortality and
inequalities, while resulting in substantial annual savings.
PMID- 27613768
TI - The effects of breastfeeding on childhood BMI: a propensity score matching
approach.
AB - Background: Many studies have found a statistical association between
breastfeeding and childhood adiposity. This paper investigates whether
breastfeeding has an effect on subsequent childhood body mass index (BMI) using
propensity scores to account for confounding. Methods: We use data from the
Millennium Cohort Study, a nationally representative UK cohort survey, which
contains detailed information on infant feeding and childhood BMI. Propensity
score matching is used to investigate the mean BMI in children breastfed
exclusively and partially for different durations of time. Results: We find
statistically significant influences of breastfeeding on childhood BMI,
particularly in older children, when breastfeeding is prolonged and exclusive. At
7 years, children who were exclusively breastfed for 16 weeks had a BMI 0.28
kg/m2 (95% confidence interval 0.07 to 0.49) lower than those who were never
breastfed, a 2% reduction from the mean BMI of 16.6 kg/m2. Conclusions: For this
young cohort, even small effects of breastfeeding on BMI could be important. In
order to reduce BMI, breastfeeding should be encouraged as part of wider
lifestyle intervention. This evidence could help to inform public health bodies
when creating public health guidelines and recommendations.
PMID- 27613769
TI - Letter by Alfonso et al Regarding Article, "Comparison of the Efficacy of
Paclitaxel-Eluting Balloon Catheters and Everolimus-Eluting Stents in the
Treatment of Coronary In-Stent Restenosis: The Treatment of In-Stent Restenosis
Study".
PMID- 27613770
TI - Response by Pleva et al to Letter Regarding Article, "Comparison of the Efficacy
of Paclitaxel-Eluting Balloon Catheters and Everolimus-Eluting Stents in the
Treatment of Coronary In-Stent Restenosis: The Treatment of In-Stent Restenosis
Study".
PMID- 27613771
TI - Age-Dependent Predictive Value of Endothelial Dysfunction for Arrhythmia
Recurrence Following Pulmonary Vein Isolation.
AB - BACKGROUND: The mechanisms of atrial fibrillation (AF) are highly divergent. The
prevalence of AF increases significantly with age, and underling mechanisms might
vary with age. Endothelial dysfunction may be associated with AF and atrial
arrhythmia recurrence after catheter ablation. We tested the hypothesis that the
impact of endothelial dysfunction on arrhythmia recurrence following catheter
ablation is age dependent. METHODS AND RESULTS: This study enrolled 92
participants with AF undergoing catheter ablation. Endothelial function was
assessed by peripheral arterial tonometry before ablation, and the natural
logarithmic transformation of reactive hyperemia index was calculated.
Endothelial dysfunction was defined as a natural logarithmic transformation of
reactive hyperemia index <0.618 (median). Participants were followed for atrial
tachycardia, flutter, and fibrillation recurrence for a median of 14 months. The
mean age was 57+/-10 years. There was significant interaction between age and
endothelial dysfunction in association with recurrence of AF (P=0.029) and any
atrial arrhythmia (P=0.015), and the risk associated with endothelial dysfunction
for arrhythmia recurrence was higher in younger versus older participants.
Participants were divided into 2 age groups at a threshold of 60 years. Among
participants aged <=60 years, multivariate Cox proportional hazards analysis
revealed the independent association between endothelial dysfunction and
increased risk of arrhythmia recurrence (hazard ratio for AF 4.18 [95% CI 1.33
15.82], P=0.014, and for any atrial arrhythmia 3.62 [95% CI 1.29-11.81],
P=0.014). Kaplan-Meier analysis showed that participants with endothelial
dysfunction had significantly higher rates of recurrence of AF (P=0.01) and any
atrial arrhythmia (P=0.002). CONCLUSIONS: The risk associated with endothelial
dysfunction for arrhythmia recurrence following catheter ablation was age
dependent and was higher in younger participants.
PMID- 27613774
TI - The Role of Cognitive Bias in Suboptimal HPV Vaccine Uptake.
PMID- 27613772
TI - Protein Carbonylation of an Amino Acid Residue of the Na/K-ATPase alpha1 Subunit
Determines Na/K-ATPase Signaling and Sodium Transport in Renal Proximal Tubular
Cells.
AB - BACKGROUND: We have demonstrated that cardiotonic steroids, such as ouabain,
signaling through the Na/K-ATPase, regulate sodium reabsorption in the renal
proximal tubule. By direct carbonylation modification of the Pro222 residue in
the actuator (A) domain of pig Na/K-ATPase alpha1 subunit, reactive oxygen
species are required for ouabain-stimulated Na/K-ATPase/c-Src signaling and
subsequent regulation of active transepithelial (22)Na(+) transport. In the
present study we sought to determine the functional role of Pro222 carbonylation
in Na/K-ATPase signaling and sodium handling. METHODS AND RESULTS: Stable pig
alpha1 knockdown LLC-PK1-originated PY-17 cells were rescued by expressing wild
type rat alpha1 and rat alpha1 with a single mutation of Pro224 (corresponding to
pig Pro222) to Ala. This mutation does not affect ouabain-induced inhibition of
Na/K-ATPase activity, but abolishes the effects of ouabain on Na/K-ATPase/c-Src
signaling, protein carbonylation, Na/K-ATPase endocytosis, and active
transepithelial (22)Na(+) transport. CONCLUSIONS: Direct carbonylation
modification of Pro224 in the rat alpha1 subunit determines ouabain-mediated Na/K
ATPase signal transduction and subsequent regulation of renal proximal tubule
sodium transport.
PMID- 27613773
TI - Relation of Body Mass Index With Adverse Outcomes Among Patients With Atrial
Fibrillation: A Meta-Analysis and Systematic Review.
AB - BACKGROUND: Several studies have investigated the impact of body mass index (BMI)
on the prognosis of atrial fibrillation, but the results remain controversial. We
sought to estimate the association of BMI with atrial fibrillation-related
outcomes. METHODS AND RESULTS: We systematically searched the Cochrane Library,
PubMed, and Elsevier databases for all studies reporting associations between BMI
and atrial fibrillation-related outcomes. Relative risks (RRs) and 95% CIs were
extracted and pooled. Nine studies with 49 364 participants were included.
Underweight BMI was associated with an increased risk of stroke or systemic
embolism (RR 1.67, 95% CI 1.12-2.49), all-cause mortaliity (RR 2.61, 95% CI 2.21
3.09), and cardiovascular death (RR 2.49, 95% CI 1.38-4.50). Nevertheless, the
pooled RRs of overweight and obese patients were lower than those of normal
weight patients for stroke or systemic embolism (overweight: RR 0.91, 95% CI 0.80
1.04; obese: RR 0.84, 95% CI 0.72-0.98; grade 1 obesity: RR 0.89, 95% CI 0.71
1.11; grade 2 obesity: RR 0.64, 95% CI 0.45-0.91; grade 3 obesity: RR 0.82, 95%
CI 0.54-1.25), all-cause death (overweight: RR 0.78, 95% CI 0.62-0.96; obese: RR
0.84, 95% CI 0.64-1.10; grade 1 obesity: RR 0.64, 95% CI 0.57-0.73; grade 2
obesity: RR 0.70, 95% CI 0.47-1.03; grade 3 obesity: RR 0.72, 95% CI 0.59-0.88),
and cardiovascular death (overweight: RR 0.79, 95% CI 0.58-1.08; obese: RR 0.99,
95% CI 0.79-1.24). CONCLUSIONS: Underweight BMI is associated with an increased
risk of stroke or systemic embolism, cardiovascular death, and all-cause death in
Asian patients with atrial fibrillation, whereas in all atrial fibrillation
patients, overweight and obese BMI was not associated with increased risks of
these outcomes.
PMID- 27613776
TI - Global Spread of the Community-Associated Methicillin-Resistant Staphylococcus
aureus USA300 Latin American Variant.
PMID- 27613777
TI - Reply to Planet et al.
PMID- 27613775
TI - HIV Suppression Restores the Lung Mucosal CD4+ T-Cell Viral Immune Response and
Resolves CD8+ T-Cell Alveolitis in Patients at Risk for HIV-Associated Chronic
Obstructive Pulmonary Disease.
AB - BACKGROUND: Lung CD4+ T-cell depletion and dysfunction, CD8+ T-cell alveolitis,
smoking, and poor control of human immunodeficiency virus (HIV) are features of
HIV-associated chronic obstructive pulmonary disease (COPD), but these changes
have not been evaluated in smokers at risk for COPD. We evaluated the impact of
viral suppression following initiation of antiretroviral therapy (ART) on HIV
specific immunity and the balance of the CD4+ T-cell to CD8+ T-cell ratio in the
lung. METHODS: Using flow cytometry, we assessed the T-cell immune response in
lung and blood specimens obtained from 12 actively smoking HIV-positive patients
before ART initiation and after ART-associated viral suppression. RESULTS: HIV
suppression resulted in enhanced lung and systemic HIV-specific CD4+ T-cell
immune responses without significant changes in CD8+ T-cell responses. We
observed an increase in lung ratios of CD4+ T cells to CD8+ T cells and CD4+ T
cell frequencies, decreased CD8+ T-cell numbers, and resolution of CD8+ T-cell
alveolitis after ART in 9 of 12 individuals. Viral suppression reduced Fas
receptor and programmed death 1 expression in lung CD4+ T cells, correlating with
enhanced effector function and reduced susceptibility to apoptosis. HIV
suppression rescued peripheral but not lung HIV-specific CD4+ T-cell
proliferation, resulting in augmented effector multifunction. DISCUSSION:
Together, our results demonstrate that HIV suppression restores lung mucosal HIV
specific CD4+ T-cell multifunctional immunity and balance in the ratio of CD4+ T
cells to CD8+ T cells, often resolving CD8+ T-cell alveolitis in active smokers.
Peripheral expansion and redistribution of CD4+ T cells and increased resistance
to apoptosis are 2 mechanisms contributing to immunologic improvement following
viral suppression in patients at risk for HIV-associated COPD.
PMID- 27613778
TI - Allocation of Resources to Communication of Research Result Summaries.
AB - Researchers and policymakers recommend communicating summary research results to
biobank participants when feasible. To date, however, there have been few
explorations of participant preferences for dedicating resources to this
activity. Fifteen semi-structured interviews were conducted with participants of
a genetic medicine biobank. Participants were interviewed by phone about their
motivation for participation, and opinions about the allocation of resources to
communicating summary results. De-identified transcripts were used for a directed
content analysis. Most biobank participation was altruistic. All participants
were not only interested in receiving summary results but also expressed a clear
preference for allocating limited funds to conducting additional genetic
research. The results suggest that participants have a nuanced view about the
allocation of biobank resources to returning summary results, and asking their
opinion is a valuable exercise. Researchers may benefit from transparency about
research goals and involving biobank participants in decisions about return of
summary results.
PMID- 27613779
TI - Ethical challenges facing veterinary professionals in Ireland: results from
Policy Delphi with vignette methodology.
AB - Ethics is key to the integrity of the veterinary profession. Despite its
importance, there is a lack of applied research on the range of ethical
challenges faced by veterinarians. A three round Policy Delphi with vignette
methodology was used to record the diversity of views on ethical challenges faced
by veterinary professionals in Ireland. Forty experts, comprising veterinary
practitioners, inspectors and nurses, accepted to participate. In round 1, twenty
vignettes describing a variety of ethically challenging veterinary scenarios were
ranked in terms of ethical acceptability, reputational risk and perceived
standards of practice. Round 2 aimed at characterising challenges where future
policy development or professional guidance was deemed to be needed. In round 3,
possible solutions to key challenges were explored. Results suggest that current
rules and regulations are insufficient to ensure best veterinary practices and
that a collective approach is needed to harness workable solutions for the
identified ethical challenges. Challenges pertaining mostly to the food chain
seem to require enforcement measures whereas softer measures that promote
professional discretion were preferred to address challenges dealing with
veterinary clinical services. These findings can support veterinary
representative bodies, advisory committees and regulatory authorities in their
decision making, policy and regulation.
PMID- 27613780
TI - Authoritarian parenting predicts reduced electrocortical response to observed
adolescent offspring rewards.
AB - Parenting styles are robust predictors of offspring outcomes, yet little is known
about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage
of adolescent = 12.9) completed a laboratory guessing task while EEG was
continuously recorded. In the task, each pair member received feedback about
their own monetary wins and losses and also observed the monetary wins and losses
of the other member of the pair. We examined the association between self
reported parenting style and parents' electrophysiological responses to watching
their adolescent winning and losing money, dubbed the observational Reward
Positivity (RewP) and observational feedback negativity (FN), respectively. Self
reported authoritarian parenting predicted reductions in parents' observational
RewP but not FN. This predictive relationship remained after adjusting for sex of
both participants, parents' responsiveness to their own wins, and parental
psychopathology. 'Exploratory analyses found that permissive parenting was
associated with a blunting of the adolescents' response to their parents'
losses'. These findings suggest that parents' rapid neural responses to their
child's successes may relate to the harsh parenting behaviors associated with
authoritarian parenting.
PMID- 27613782
TI - Evidence, Engagement, and Technology: Themes of and the State of Primary Care
Practice-based Network Research.
AB - Practice-based research supported by practice-based research network (PBRN)
infrastructure has historically provided an important method for challenging
guidelines and evidence arising from secondary and tertiary care settings. This
sample of current practice-based research in this issue of the JABFM provides an
opportunity to ask whether practice-based research continues to address questions
relevant to primary care practices and clinicians and whether a PBRN
infrastructure is instrumental to maintaining the relevance and feasibility of
practice-based research. Based on this issue's articles, the current state of
practice-based research seems to be good, at face value addressing relevant
issues for primary care practices. Less clear is the degree to which PBRN
infrastructures and relationships informed the questions asked and facilitated
the implementation of the studies presented. Practice-based research-related
articles that routinely report about how study questions arose-from practices and
their clinicians, staff and communities, or elsewhere-could help directly answer
questions of relevance. In addition, reporting how practices are recruited to
practice-based research studies could inform the degree to which ongoing
relationships central to PBRNs facilitate the recruitment and conduct of practice
based research.
PMID- 27613781
TI - Action-based touch observation in adults with high functioning autism: Can
compromised self-other distinction abilities link social and sensory everyday
problems?
AB - Next to social problems, individuals with autism spectrum disorder (ASD) often
report severe sensory difficulties. Altered processing of touch is however a
stronger mediator of social symptoms' severity than altered processing of for
instance vision or audition. Why is this the case? We reasoned that sensory
difficulties may be linked to social problems in ASD through insufficient self
other distinction centred on touch. We investigated by means of EEG whether the
brain of adults with ASD adequately signals when a tactile consequence of an
observed action does not match own touch, as compared to the brain of matched
controls. We employed the action-based somatosensory congruency paradigm.
Participants observed a human or wooden hand touching a surface, combined with a
tap-like tactile sensation that either matched or mismatched the tactile
consequence of the observed movement. The ASD group showed a diminished
congruency effect for human hands only in the P3-complex, suggesting difficulties
with signalling observed action-based touch of others that does not match own
touch experiences. Crucially, this effect reliably correlated with self-reported
social and sensory everyday difficulties in ASD. The findings might denote a
novel theoretical link between sensory and social impairments in the autism
spectrum.
PMID- 27613783
TI - Where You Stand Is What You See: We See a Need for More Primary Care Research
Funding.
PMID- 27613784
TI - Lost in Translation: NIH Funding for Family Medicine Research Remains Limited.
AB - Departments of Family Medicine (DFMs) in the United States consistently received
around 0.2% of total research funding dollars and 0.3% of all awards awarded by
the National Institutes of Health (NIH) across the years 2002 to 2014. We used
the NIH Reporter tool to quantify the amount of funding and the number of grants
received by DFMs from the NIH from 2002 to 2014, using criteria similar to those
applied by previous researchers. NIH funding to DFMs as remained fairly
consistent across the time period, at roughly 0.2% of total NIH funding and 0.3%
of total grants awarded. Changing these proportions will likely require
considerable effort to build research capacity within DFMs and their frontline
practice research networks, and to shift policymaker and funder perceptions of
the value of the FM research enterprise.
PMID- 27613785
TI - Federal Research Funding for Family Medicine: Highly Concentrated, with
Decreasing New Investigator Awards.
AB - A small proportion of National Institutes of Health and other federal research
funding is received by university departments of family medicine, the largest
primary care specialty. That limited funding is also concentrated, with roughly a
quarter of all National Institutes of Health, Centers for Disease Control and
Prevention, and Agency for Healthcare Research and Quality funding awarded to 3
departments, almost half of that funding coming from 3 agencies, and a recent
trend away from funding for new investigators.
PMID- 27613786
TI - A Practice Facilitation and Academic Detailing Intervention Can Improve Cancer
Screening Rates in Primary Care Safety Net Clinics.
AB - BACKGROUND: Despite the current evidence of preventive screening effectiveness,
rates of breast, cervical, and colorectal cancer in the United States fall below
national targets. We evaluated the efficacy and feasibility of combining practice
facilitation and academic detailing quality improvement (QI) strategies to help
primary care practices increase breast, cervical, and colorectal cancer screening
among patients. METHODS: Practices received a 1-hour academic detailing session
addressing current cancer screening guidelines and best practices, followed by 6
months of practice facilitation to implement evidence-based interventions aimed
at increasing patient screening. One-way repeated measures analysis of variance
compared screening rates before and after the intervention, provider surveys, and
TRANSLATE model scores. Qualitative data were gathered via participant focus
groups and interviews. RESULTS: Twenty-three practices enrolled in the project: 4
federally qualified health centers, 10 practices affiliated with larger health
systems, 4 physician-owned practices, 4 university hospital clinics, and 1
nonprofit clinic. Average screening rates for breast cancer increased by 13% (P =
.001), and rates for colorectal cancer increased by 5.6% (P = .001). Practices
implemented a mix of electronic health record data cleaning workflows, provider
audits and feedback, reminder systems streamlining, and patient education and
outreach interventions. Practice facilitators assisted practices in tailoring
interventions to practice-specific priorities and constraints and in connecting
with community resources. Practices with resource constraints benefited from the
engagement of all levels of staff in the quality improvement processes and from
team-based adaptations to office workflows and policies. Many practices aligned
quality improvement interventions in this project with patient-centered medical
home and other regulatory reporting targets. CONCLUSIONS: Combining practice
facilitation and academic detailing is 1 method through which primary care
practices can achieve systems-level changes to better manage patient population
health.
PMID- 27613787
TI - Local Learning Collaboratives to Improve Quality for Chronic Kidney Disease
(CKD): From Four Regional Practice-based Research Networks (PBRNs).
AB - BACKGROUND: Four practice-based research networks (PBRNs) participated in a
project to increase the diffusion of evidence-based treatment guidelines for
chronic kidney disease (CKD). A multicomponent organizational intervention
engaged regionally proximal primary care practices in a series of facilitated
meetings, referred to as local learning collaboratives (LLCs). METHODS: The 2
wave strategy began with 8 practices in each PBRN receiving practice facilitation
and subsequently joining an LLC. A sequential mixed-methods design addressed the
conduct, content, and fidelity of the intervention; clinicians in 2 PBRNs
participated in interviews, and PBRN coordinators reflected on implementation
challenges. RESULTS: LLCs were formed in 3 PBRNs, with 121 monthly meetings held
across 20 LLCs. Slightly more than half of the participants were clinicians.
Qualitative data suggest that clinicians increased the priority for CKD care,
improved knowledge and skills, were satisfied with the project, and attempted to
improve care. Implementation challenges were encountered and concerns about
sustainability expressed. CONCLUSION: While PBRNs can successfully leverage
resources to diffuse treatment guidelines, and LLCs are well-accepted by clinical
staff, the formation of LLCs was not feasible for 1 PBRN, and others struggled to
meet regularly and have performance data available despite logistic support.
PMID- 27613788
TI - Decision-to-Implement Worksheet for Evidence-based Interventions: From the WWAMI
Region Practice and Research Network.
AB - BACKGROUND: Health-related scientific discoveries are often not applied in
clinical settings after publication, even when recommended by a trusted journal
or professional association. This article describes an assessment tool we
developed for use by primary care clinicians and practice administrators to
evaluate whether to implement recommended evidence-based interventions in their
practices. METHODS: We used dissemination and implementation theory to develop a
worksheet to guide decision making about whether interventions are suitable for
implementation in primary care practice settings. We tested the tool by analyzing
how members of a primary care practice-based research network rated 4 evidence
based interventions. RESULTS: The median likelihood of implementation ranged from
2 to 3.5 on a scale of 1 (low) to 5 (high). Raters' level of agreement with
statements about 3 intervention characteristics was associated (P < .05) with a
higher likelihood of implementation using Spearman rank-order correlation: simple
to implement, testable before fully implementing, and modifiable to meet the
needs of the practice. Raters found the worksheet helpful in thinking through
potential implementation, especially the prompts about modifiability and
relevance to the practice's patients and priorities. CONCLUSIONS: The Decision-to
Implement Worksheet provides a new resource for primary care practices that want
to assess whether evidence-based interventions are suitable to adopt or adapt to
meet their needs.
PMID- 27613789
TI - Clarifying Parents' and Pediatricians' Views of Partnership.
AB - PURPOSE: Given the importance of partnership in improving health care outcomes
among children, there is a substantial need to understand better what partnership
means to parents and physicians. The goal of this study was to develop a
partnership survey that was based on parents' and pediatricians' opinions about
the key concepts of partnership. METHODS: Parents of patients visiting an
affluent suburban private practice and a federally qualified health center, and 2
groups of pediatricians, were asked to review 61 partnership concepts and
identify those they considered as being important to partnership. RESULTS:
Parents and pediatricians from both practices agreed that 42 (68.9%) of the
concepts were important to partnership. Sixteen of these concepts were dropped
because they were redundant. Parents from both the suburban practice and health
center identified 5 (8.2%) concepts that they believed contributed to
partnership. Seven (11.5%) concepts were viewed as important to parents and
pediatricians from the suburban practice but not to parents from the health
center. Significant socioeconomic differences between the 2 parent groups
suggested factors that explained the differences between parent groups.
CONCLUSION: The 38 concepts endorsed by parents and pediatricians provided a
nuanced view of partnership and formed the Parent Pediatrician Partnership
Survey.
PMID- 27613790
TI - Primary Care Patients' Willingness to Participate in Comprehensive Weight Loss
Programs: From the WWAMI Region Practice and Research Network.
AB - PURPOSE: In the United States, 69% of adults are overweight or obese, as defined
by a body mass index (BMI) >=25 kg/m(2). The US Preventive Services Task Force
recommends screening all adult patients for obesity and referring obese patients
to intensive, multicomponent behavioral weight loss programs comprising 12 to 26
yearly sessions. The objective of this study is to determine the degree to which
overweight and obese primary care patients report willingness to participate in
these intensive weight loss programs and to identify the patient factors
associated with reported willingness to participate. METHODS: This 2013 cross
sectional survey was offered to all adult patients seen for an office visit at 1
of 12 primary care clinics in the Washington, Wyoming, Alaska, Montana and Idaho
(WWAMI) Region Practice and Research Network (WPRN). Patients self-reported both
their health information and their willingness to participate in a comprehensive
weight loss program. Respondents were characterized by descriptive statistics. We
compared reported rates of willingness to participate by patient factors and
assessed which patient factors were independently associated with reported
willingness using bivariate analysis and logistic regression, respectively.
RESULTS: Of overweight and obese respondents, 63% reported willingness to
participate in comprehensive weight loss programs. Age, sex, race/ethnicity,
insurance status, BMI, and reason for wanting to lose weight were all
significantly and independently associated with reported willingness to
participate. CONCLUSIONS: Reported willingness to participate in comprehensive
weight loss programs suggests that additional resources are needed to understand
strategies for disseminating and implementing effective comprehensive weight loss
programs.
PMID- 27613791
TI - Implementation of Technology-based Patient Engagement Strategies within Practice
based Research Networks.
AB - BACKGROUND: Technology-based patient engagement strategies (such as patient
portals) are increasingly available, yet little is known about current use and
barriers within practice-based research networks (PBRNs). PBRN directors have
unique opportunities to inform the implementation of patient-facing technology
and to translate these findings into practice. METHODS: PBRN directors were
queried regarding technology-based patient engagement strategies as part of the
2015 CAFM Educational Research Alliance (CERA) survey of PBRN directors. A total
of 102 PBRN directors were identified via the Agency for Healthcare Research and
Quality's registry; 54 of 96 eligible PBRN directors completed the survey, for a
response rate of 56%. RESULTS: Use of technology-based patient engagement
strategies within PBRNs was limited, with less than half of respondents reporting
experience with the most frequently named tools (risk assessments/decision aids).
Information technology (IT) support was the top barrier, followed by low rates of
portal enrollment. For engaging participant practices, workload and practice
leadership were cited as most important, with fewer respondents noting concerns
about patient privacy. DISCUSSION: Given limited use of patient-facing
technologies, PBRNs have an opportunity to clarify the optimal use of these
strategies. Providing IT support and addressing clinician concerns regarding
workload may facilitate the inclusion of innovative technologies in PBRNs.
PMID- 27613792
TI - Patterns of Electronic Portal Use among Vulnerable Patients in a Nationwide
Practice-based Research Network: From the OCHIN Practice-based Research Network
(PBRN).
AB - BACKGROUND: Underserved patient populations experience barriers to accessing and
engaging within the complex health care system. Electronic patient portals have
been proposed as a potential new way to improve access and engagement. We studied
patient portal use for 12 consecutive months (365 days) among a large, nationally
distributed, underserved patient population within the OCHIN (originally created
as the Oregon Community Health Information Network and renamed OCHIN as other
states joined) practice-based research network (PBRN). METHODS: We
retrospectively assessed adoption and use of Epic's MyChart patient portal in the
first 12 months after MyChart was made available to the OCHIN PBRN. We examined
electronic health record data from 36,549 patients aged >=18 years who were
offered a MyChart access code between May 1, 2012, and April 30, 2013, across the
OCHIN PBRN in 13 states. RESULTS: Overall, 29% of patients offered an access code
logged into their MyChart account. Superusers (minimum of 2 logins per month over
a 12-month period) accounted for 6% of users overall. Men, nonwhite patients,
Hispanic patients, Spanish-speaking patients, and those with the lowest incomes
were significantly less likely to activate. Publicly insured and uninsured
patients were also less likely to log in to their MyChart account, but once
activated they were more likely than privately insured patients to use MyChart
functions. CONCLUSIONS: Our findings suggest that, compared with others, certain
patient groups may be less interested in using patient portals or may have
experienced significant barriers that prevented use. Making portal access
available is a first step. Additional studies need to specifically identify
health system-, clinic-, and patient-level barriers and facilitators to portal
adoption and use.
PMID- 27613793
TI - Use of Clinical Decision Support to Improve Primary Care Identification and
Management of Chronic Kidney Disease (CKD).
AB - BACKGROUND: Early detection of chronic kidney disease (CKD) can lead to
interventions to prevent renal failure and reduce risk for cardiovascular
disease, yet adherence to treatment goals is suboptimal in the primary care
setting. The purpose of this study was to assess whether clinical decision
support (CDS) can be used to improve the identification and management of CKD.
METHODS: This 2 year demonstration study was conducted in 11 primary care PPRNet
practices. CDS included a risk assessment tool, health maintenance protocols,
flow chart and a patient registry. Practices received performance reports and
hosted annual half day on-site visits. RESULTS: There were statistically
significant increases in screening for albuminuria (median 24 month change 30%, p
< 0.0005) and monitoring albuminuria (median 24 month change 25%, p < 0.0005). An
absolute 23.5% improvement in appropriate use of ACE-inhibitor or angiotensin
receptor blocker and an absolute 7.0% improvement in hemoglobin measurement were
not statistically significant. There were no clinical or statistically
significant differences in other CKD CQMs. Facilitators to CDS use included
practices' prioritization of improving CKD and staff use of standing orders.
Barriers included incorporating use into existing workflow and variable use among
providers. CONCLUSIONS: Use of CDS to improve CKD identification and management
in primary care practices shows promise. However, other barriers must be
addressed to effectively achieve improvements in CKD outcomes.
PMID- 27613794
TI - Patient-Provider Communication: Does Electronic Messaging Reduce Incoming
Telephone Calls?
AB - PURPOSE: Internet-based patient portals are increasingly being implemented
throughout health care organizations to enhance health and optimize communication
between patients and health professionals. The decision to adopt a patient portal
requires careful examination of the advantages and disadvantages of
implementation. This study aims to investigate 1 proposed advantage of
implementation: alleviating some of the clinical workload faced by employees.
METHODS: A retrospective time-series analysis of the correlation between the rate
of electronic patient-to-provider messages-a common attribute of Internet-based
patient portals-and incoming telephone calls. The rate of electronic messages and
incoming telephone calls were monitored from February 2009 to June 2014 at 4
economically diverse clinics (a federally qualified health center, a rural health
clinic, a community-based clinic, and a university-based clinic) related to 1
university hospital. RESULTS: All 4 clinics showed an increase in the rate of
portal use as measured by electronic patient-to-provider messaging during the
study period. Electronic patient-to-provider messaging was significantly
positively correlated with incoming telephone calls at 2 of the clinics (r =
0.546, P < .001 and r = 0.543, P < .001). The remaining clinics were not
significantly correlated but demonstrated a weak positive correlation (r = 0.098,
P = .560 and r = 0.069, P = .671). CONCLUSIONS: Implementation and increased use
of electronic patient-to-provider messaging was associated with increased use of
telephone calls in 2 of the study clinics. While practices are increasingly
making the decision of whether to implement a patient portal as part of their
system of care, it is important that the motivation behind such a change not be
based on the idea that it will alleviate clinical workload.
PMID- 27613795
TI - Implementation of a New Kiosk Technology for Blood Pressure Management in a
Family Medicine Clinic: from the WWAMI Region Practice and Research Network.
AB - BACKGROUND: Using a self-service kiosk to measure blood pressure (BP) has the
potential to increase patients' awareness of their BP control and free up medical
assistant (MA) time. The objective of this study was to evaluate BP kiosk
acceptability and usability, as well as its effects on the workflow of patient BP
self-measurement in a primary care clinic. METHODS: We used qualitative and
quantitative assessments of kiosk implementation via meetings with clinic
leaders, focus groups with clinic providers and staff, observations of kiosk
users, and surveys of kiosk users at 2 and 8 months. RESULTS: Most patients were
comfortable using the kiosk (82% at 2 months, 87% at 8 months). Initial provider
concerns included accuracy, but most gained confidence after comparing it with
other monitors and reviewing the literature supporting its accuracy. Patients and
providers saw many benefits: easier BP checks, increased patient engagement, and
saved MA time for other tasks. The clinic addressed early concerns (eg, infection
control, confusing instructions, perceived loss of personal touch). Most patients
(86%) supported the clinic continuing to use the kiosks. CONCLUSIONS: Providers,
staff, and patients adapted to the use of BP kiosks, providing value by engaging
patients in their own care and saving MA time. The clinic decided to keep the
self-service kiosk after the pilot period.
PMID- 27613797
TI - Real Life Is Full of Choices.
PMID- 27613796
TI - Practice-based Research Networks (PBRNs) Bridging the Gaps between Communities,
Funders, and Policymakers.
AB - In this commentary, we propose that practice-based research networks (PBRNs)
engage with funders and policymakers by applying the same engagement strategies
they have successfully used to build relationships with community stakeholders. A
community engagement approach to achieve new funding streams for PBRNs should
include a strategy to engage key stakeholders from the communities of funders,
thought leaders, and policymakers using collaborative principles and methods.
PBRNs that implement this strategy would build a robust network of engaged
partners at the community level, across networks, and would reach state and
federal policymakers, academic family medicine departments, funding bodies, and
national thought leaders in the redesign of health care delivery.
PMID- 27613798
TI - IVF, same-sex couples and the value of biological ties.
AB - Ought parents, in general, to value being biologically tied to their children? Is
it important, in particular, that both parents be biologically tied to their
children? I will address these fundamental questions by looking at a fairly new
practice within IVF treatments, so-called IVF-with-ROPA (Reception of Oocytes
from Partner), which allows lesbian couples to 'share motherhood', with one
partner providing the eggs while the other becomes pregnant. I believe that IVF
with-ROPA is, just like other IVF treatments, morally permissible, but here I
argue that the increased biological ties which IVF-with-ROPA allows for do not
have any particular value beside the satisfaction of a legitimate wish, because
there is no intrinsic value in a biological tie between parents and children;
further, I argue that equality within parental projects cannot be achieved by
redistributing biological ties.
PMID- 27613799
TI - Two conceptions of conscience and the problem of conscientious objection.
AB - Schuklenk and Smalling argue that it is practically impossible for civic
institutions to meet the conditions necessary to ensure that conscientious
objection does not conflict with the core principles of liberal democracies. In
this response, I propose an alternative definition of conscience to that offered
by Schuklenk and Smalling. I discuss what I call the 'traditional' notion of
conscience, and contrast this with the existentialist conception of conscience
(which I take to be a close cousin of the view targeted by Schuklenk and
Smalling). I argue that the traditional notion, grounded in an objective moral
order, avoids the criticisms advanced by Schuklenk and Smalling; the
existentialist conception, in contrast, does not. I conclude by discussing the
benefits and risks of a 'restricted view' of respect for conscience.
PMID- 27613801
TI - Neutral oligosaccharides in feces of breastfed and formula-fed infants at
different ages.
AB - Beneficial effects have been proposed for human milk oligosaccharides (HMO), as
deduced from in vitro and animal studies. To date, in vivo evidence of the link
between certain oligosaccharide structures in milk and their consumption by
infant gut microbiota is still missing, although likely. Whereas many studies
have described HMO patterns in human milk from larger cohorts, data on the
excretion of HMO and possible metabolites produced in the infant gut are still
very limited. From smaller-scale studies, an age-dependency according to infant
gut maturation and microbiota adaptation has previously been hypothesized. To
further investigate this, we profiled neutral fecal oligosaccharides from term
born infants who were exclusively breastfed, formula-fed or mixed-fed at the age
of 2 months, and from a follow-up of a subgroup at 7 months of age (INFABIO
study). Data on maternal antibiotic exposure was also included. Automated matrix
assisted laser desorption/ionization-time-of-flight mass spectrometry analyses
revealed the presence of HMO and metabolites in the feces of most, but not all
breastfed infants at 2 months, with highly varying patterns that appeared not to
differ with maternal antibiotics exposure. Formula-fed infants at 2 months and
most of the breastfed infants at 7 months did not excrete HMO-like structures in
their feces, the latter corresponding to the hypothesis of age-dependency.
Together with our previous results that were partly contradictory to what has
been proposed by others, here, we suggest alternative explanations for the
described association of oligosaccharide excretion with age and feeding type in
infants below 7 months of age.
PMID- 27613800
TI - Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice
and by diet with a high n-6/n-3 PUFA ratio.
AB - In mammals, because they share a single synthetic pathway, n-6/n-3 ratios of
dietary PUFAs impact tissue arachidonic acid (ARA) and DHA content. Likewise,
SNPs in the human fatty acid desaturase (FADS) gene cluster impact tissue ARA and
DHA. Here we tested the feasibility of using heterozygous Fads2-null-mice (HET)
as an animal model of human FADS polymorphisms. WT and HET mice were fed diets
with linoleate/alpha-linolenate ratios of 1:1, 7:1, and 44:1 at 7% of diet. In WT
liver, ARA and DHA in phospholipids varied >2* among dietary groups, reflecting
precursor ratios. Unexpectedly, ARA content was only <10% lower in HET than in WT
livers, when fed the 44:1 diet, likely due to increased Fads1 mRNA in response to
reduced Fads2 mRNA in HET. Consistent with the RNA data, C20:3n-6, which is
elevated in minor FADS haplotypes in humans, was lower in HET than WT. Diet and
genotype had little effect on brain PUFAs even though brain Fads2 mRNA was low in
HET. No differences in cytokine mRNA were found among groups under unstimulated
conditions. In conclusion, differential PUFA profiles between HET mice and human
FADS SNPs suggest low expression of both FADS1 and 2 genes in human minor
haplotypes.
PMID- 27613803
TI - Discovery and characterization of de novo sialic acid biosynthesis in the phylum
Fusobacterium.
AB - Sialic acids are nine-carbon backbone carbohydrates found in prominent outermost
positions of glycosylated molecules in mammals. Mimicry of sialic acid (N
acetylneuraminic acid, Neu5Ac) enables some pathogenic bacteria to evade host
defenses. Fusobacterium nucleatum is a ubiquitous oral bacterium also linked with
invasive infections throughout the body. We employed multidisciplinary approaches
to test predictions that F. nucleatum engages in de novo synthesis of sialic
acids. Here we show that F. nucleatum sbsp. polymorphum ATCC10953 NeuB (putative
Neu5Ac synthase) restores Neu5Ac synthesis to an Escherichia coli neuB mutant.
Moreover, purified F. nucleatum NeuB participated in synthesis of Neu5Ac from N
acetylmannosamine and phosphoenolpyruvate in vitro Further studies support the
interpretation that F. nucleatum ATCC10953 NeuA encodes a functional CMP-sialic
acid synthetase and suggest that it may also contain a C-terminal sialic acid O
acetylesterase. We also performed BLAST queries of F. nucleatum genomes,
revealing that only 4/31 strains encode a complete pathway for de novo Neu5Ac
synthesis. Biochemical studies including mass spectrometry were consistent with
the bioinformatic predictions, showing that F. nucleatum ATCC10953 synthesizes
high levels of Neu5Ac, whereas ATCC23726 and ATCC25586 do not express detectable
levels above background. While there are a number of examples of sialic acid
mimicry in other phyla, these experiments provide the first biochemical and
genetic evidence that a member of the phylum Fusobacterium can engage in de novo
Neu5Ac synthesis.
PMID- 27613805
TI - Social isolation impairs remyelination in mice through modulation of IL-6.
AB - Recent studies have revealed that social experience affects myelination. These
findings have important implications for disorders that feature abnormal
myelination, such as multiple sclerosis (MS), as previous studies have shown that
psychosocial stress exacerbates the pathobiology of MS. However, most studies
have focused on psychosocial stress during the demyelination phase of MS and have
not investigated the effects of social experience on remyelination. Thus, the
current study sought to determine whether social experience can alter
remyelination after myelin depletion. Myelin in the mouse medial prefrontal
cortex was depleted with cuprizone, and the effects of subsequent social
isolation on remyelination were evaluated. Remyelination was severely impaired in
socially isolated mice. Social isolation also increased IL-6 levels in the medial
prefrontal cortex, and administration of an IL-6 inhibitor (ND50 = 0.01-0.03 MUg
for 0.25 ng/ml IL-6) ameliorated remyelination impairments. Consistent with this
result, IL-6 administration (ED50 = 0.02-0.06 ng/ml) disturbed remyelination. In
addition, neuron-oligodendrocyte coculture experiments showed that IL-6 treatment
(ED50 <= 0.02 ng/ml) markedly impeded myelination, which was recovered with IL-6
inhibitor administration (ND50 = 0.01-0.03 MUg for 0.25 ng/ml IL-6). This study
provides the first direct evidence, to our knowledge, that social experience
influences remyelination via modulation of IL-6 expression. These findings
indicate that psychosocial stress may disturb remyelination through regulation of
IL-6 expression in patients with such demyelinating diseases that involve
remyelination as MS.-Makinodan, M., Ikawa, D., Miyamoto, Y., Yamauchi, J.,
Yamamuro, K., Yamashita, Y., Toritsuka, M., Kimoto, S., Okumura, K., Yamauchi,
T., Fukami, S., Yoshino, H., Wanaka, A., Kishimoto, T. Social isolation impairs
remyelination in mice through modulation of IL-6.
PMID- 27613804
TI - Mitochondrial BMI1 maintains bioenergetic homeostasis in cells.
AB - The polycomb complex proto-oncogene BMI1 [B lymphoma Mo-MLV insertion region 1
homolog (mouse)] is essential for self-renewal of normal and cancer stem cells.
BMI1-null mice show severe defects in growth, development, and survival. Although
BMI1 is known to exert its effect in the nucleus via repression of 2 potent cell
cycle regulators that are encoded by the Ink4a/Arf locus, deletion of this locus
only partially rescues BMI1-null phenotypes, which is indicative of alternate
mechanisms of action of BMI1. Here, we show that an extranuclear pool of BMI1
localizes to inner mitochondrial membrane and directly regulates mitochondrial
RNA (mtRNA) homeostasis and bioenergetics. These mitochondrial functions of BMI1
are independent of its previously described nuclear functions because a nuclear
localization-defective mutant BMI1 rescued several bioenergetic defects that we
observed in BMI1-depleted cells, for example, mitochondrial respiration,
cytochrome c oxidase activity, and ATP production. Mechanistically, BMI1
coprecipitated with polynucleotide phosphorylase, a ribonuclease that is
responsible for decay of mtRNA transcripts. Loss of BMI1 enhanced ribonuclease
activity of polynucleotide phosphorylase and reduced mtRNA stability. These
findings not only establish a novel extranuclear role of BMI1 in the regulation
of mitochondrial bioenergetics, but also provide new mechanistic insights into
the role of this proto-oncogene in stem cell differentiation, neuronal aging, and
cancer.-Banerjee Mustafi, S., Aznar, N., Dwivedi, S. K. D., Chakraborty, P. K.,
Basak, R., Mukherjee, P., Ghosh, P., Bhattacharya, R. Mitochondrial BMI1
maintains bioenergetic homeostasis in cells.
PMID- 27613808
TI - Suicide voices: testimonies of trauma in the French workplace.
AB - Workplace suicide has become an urgent social concern internationally with rising
numbers of employees choosing to kill themselves in the face of extreme pressures
at work. Yet, research on this phenomenon is hampered by fragmentary statistical
data and the sheer contentiousness of this issue. This paper presents the
preliminary findings of a research project on workplace suicides in France, where
there has been a 'suicide epidemic' across a wide range of companies. I draw on
an analysis of suicide letters linked to 23 suicide cases across three French
companies during the period 2005-2015. My methodological approach is informed by
the work of suicide sociologist, Jack D Douglas, who emphasised the importance of
narrative, testimony and voice to our understanding of the causes of suicide.
Douglas argued that an analysis of the 'social meanings' of suicide should start
with a consideration of the motivations attributed to self-killing by suicidal
individuals themselves and those close to them. Why does work or conditions of
work push some individuals to take their own lives? What can the 'suicide voices'
articulated in recent testimonies tell us about the causes of workplace suicide?
In this paper, I treat suicide letters as a unique mode of testimony that can
reveal some of the profound effects of workplace transformations on subjective,
intimate and lived experiences of work. By examining French suicide testimonies,
my aim is to deepen our understanding of the nature and causes of suicide in
today's globalised workplaces.
PMID- 27613810
TI - Complications of Intra-articular Calcaneal Fractures in Adults: Key Points for
Diagnosis, Prevention, and Treatment.
AB - : Calcaneal fractures are complex injuries with high complication rates and they
can lead to serious disability. The proper management remains controversial and
complications may occur regardless of the chosen type of treatment (operative or
nonoperative). The present article reviews the studies that are related to the
complications of calcaneal fractures. The incidence, the diagnosis, the
prevention and the treatment of these complications were researched and analyzed,
with the use of PubMed database, abstracts and original articles in English than
investigate the etiology. The aim of the article is to discuss the most suitable
management of the complications of calcaneal fractures and recommend a specific
treatment as well as prevention methods. LEVELS OF EVIDENCE: Level IV.
PMID- 27613809
TI - Mfn1 Deficiency in the Liver Protects Against Diet-Induced Insulin Resistance and
Enhances the Hypoglycemic Effect of Metformin.
AB - Mitochondrial function can be influenced by mitochondrial shape and connectivity
with other cellular organelles through fusion and fission processes. Disturbances
in mitochondrial architecture and mitochondrial fusion-related genes are observed
in situations of type 2 diabetes and obesity, leading to a highly fissioned
mitochondrial network. To directly test the effect of reduced mitochondrial
fusion on hepatic metabolism, we generated mice with a liver-specific deletion of
the Mfn1 gene (Mfn1LKO) and monitored their energy homeostasis, mitochondrial
function, and susceptibility to diet-induced insulin resistance. Livers from
Mfn1LKO mice displayed a highly fragmented mitochondrial network. This was
coupled to an enhanced mitochondrial respiration capacity and a preference for
the use of lipids as the main energy source. Although Mfn1LKO mice are similar to
control mice fed a low-fat diet, they are protected against insulin resistance
induced by a high-fat diet. Importantly, Mfn1 deficiency increased complex I
abundance and sensitized animals to the hypoglycemic effect of metformin. Our
results suggest that targeting Mfn1 could provide novel avenues to ameliorate
glucose homeostasis in obese patients and improve the effectiveness of metformin.
PMID- 27613806
TI - Epistatic and Independent Effects on Schizophrenia-Related Phenotypes Following
Co-disruption of the Risk Factors Neuregulin-1 * DISC1.
AB - Few studies have addressed likely gene * gene (ie, epistatic) interactions in
mediating risk for schizophrenia. Using a preclinical genetic approach, we
investigated whether simultaneous disruption of the risk factors Neuregulin-1
(NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant
phenotypic profile different from that observed following disruption to either
gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse
inhibition, both reversed by antipsychotic treatment, and accompanied by reduced
striatal dopamine D2 receptor protein expression, impaired social cognition, and
altered glutamatergic synaptic protein expression in selected brain areas. Single
gene DISC1 mutants demonstrated a disruption in social cognition and nest
building, altered brain 5-hydroxytryptamine levels and hippocampal ErbB4
expression, and decreased cortical expression of the schizophrenia-associated
microRNA miR-29b. Co-disruption of DISC1 and NRG1, indicative of epistasis,
evoked an impairment in sociability and enhanced self-grooming, accompanied by
changes in hypothalamic oxytocin/vasopressin gene expression. The findings
indicate specific behavioral correlates and underlying cellular pathways
downstream of main effects of DNA variation in the schizophrenia-associated genes
NRG1 and DISC1.
PMID- 27613811
TI - Distraction First Metatarsophalangeal Arthrodesis With Tricortical Calcaneus
Autograft: Technique Tips.
AB - : First metatarsophalangeal joint arthritis can stem from a biomechanical
imbalance as in hallux abducto valgus, metabolic arthritidies such as rheumatoid
or gout, and even in posttraumatic cases. Advanced arthritis in the foot and
ankle can often become debilitating. Surgical intervention is often necessary.
Revision of failed first metatarsophalangeal joint arthroplasty is often in the
setting of bony erosion and lysis, cystic changes, and loss of bone stock. In
this article, we describe first metatarsophalangeal distraction arthrodesis
technique using tricortical calcaneus autograft with the aim of simplifying donor
site graft harvesting and decreasing donor site morbidity while attaining
successful osseous union. LEVELS OF EVIDENCE: Level V.
PMID- 27613807
TI - International patient and physician consensus on a psoriatic arthritis core
outcome set for clinical trials.
AB - OBJECTIVE: To identify a core set of domains (outcomes) to be measured in
psoriatic arthritis (PsA) clinical trials that represent both patients' and
physicians' priorities. METHODS: We conducted (1) a systematic literature review
(SLR) of domains assessed in PsA; (2) international focus groups to identify
domains important to people with PsA; (3) two international surveys with patients
and physicians to prioritise domains; (4) an international face-to-face meeting
with patients and physicians using the nominal group technique method to agree on
the most important domains; and (5) presentation and votes at the Outcome
Measures in Rheumatology (OMERACT) conference in May 2016. All phases were
performed in collaboration with patient research partners. RESULTS: We identified
39 unique domains through the SLR (24 domains) and international focus groups (34
domains). 50 patients and 75 physicians rated domain importance. During the March
2016 consensus meeting, 12 patients and 12 physicians agreed on 10 candidate
domains. Then, 49 patients and 71 physicians rated these domains' importance.
Five were important to >70% of both groups: musculoskeletal disease activity,
skin disease activity, structural damage, pain and physical function. Fatigue and
participation were important to >70% of patients. Patient global and systemic
inflammation were important to >70% of physicians. The updated PsA core domain
set endorsed by 90% of OMERACT 2016 participants includes musculoskeletal disease
activity, skin disease activity, pain, patient global, physical function, health
related quality of life, fatigue and systemic inflammation. CONCLUSIONS: The
updated PsA core domain set incorporates patients' and physicians' priorities and
evolving PsA research. Next steps include identifying outcome measures that
adequately assess these domains.
PMID- 27613812
TI - Effectiveness of Percutaneous Proximal Closing Wedge Osteotomy With Akin
Osteotomy to Correct Severe Hallux Valgus Determined by Radiographic Parameters.
AB - : Some authors reported the results from percutaneous distal metatarsal osteotomy
for hallux valgus recently. On the other hand, there are few reports of
percutaneous proximal metatarsal osteotomy. The purpose of the present study was
to evaluate the radiographic results of percutaneous proximal closing wedge
osteotomy with Akin osteotomy for correction of severe hallux valgus and
increasing longitudinal arch height. Consecutive 17 feet (mean age = 70.8 years)
were investigated. The mean follow-up was 22 months. Excision of medial eminence,
distal soft tissue release, and Akin osteotomy were all performed percutaneously
and concurrently. Weight-bearing anteroposterior and lateral radiographs of the
feet were acquired preoperatively and at final follow-up. On the anteroposterior
radiographs, hallux valgus angle, intermetatarsal angle, and first metatarsal
shortening were measured. On the lateral radiographs, talometatarsal angle,
calcaneal pitch angle, and first metatarsal dorsiflexion were measured. The
average improvements in hallux valgus angle and intermetatarsal angle were 27.6
degrees and 9.9 degrees , respectively. The average first metatarsal shortening
was 2.7 mm. The first metatarsal dorsiflexion improved by 2.2 degrees ; however,
other parameters did not improve significantly. In conclusion, percutaneous
proximal closing wedge osteotomy with Akin osteotomy corrects severe hallux
valgus; however, the procedure does not increase the medial longitudinal arch.
LEVELS OF EVIDENCE: Therapeutic, Level IV: Case series.
PMID- 27613813
TI - Analysis of Physiological Gait Pattern in Children Without the Influence of
Footwear.
AB - : In the literature, there have been several studies that have analyzed and
explained the characteristics of physiological gait in association with
pathologies; however, finding information about normal gait pattern while
barefoot is difficult. This study focuses on the differences in the barefoot gait
between children and adolescents. A total of 320 healthy children and adolescent
were recruited and divided into groups according to age: G1 (1-6 years), G2 (7-10
years), G3 (>11 years). Data were collected using a dynamometric platform and
analyzed using SPSS software. This study's findings indicate that there are
differences in the swing, stance, load, and single support phases of gait. To our
knowledge, this is the first study to present the values of standardized data on
barefoot gait pattern in children aged from 2 to 10 years. LEVELS OF EVIDENCE:
Diagnostic, Level IV: Case series.
PMID- 27613814
TI - A Randomized Controlled Trial Assessing the Effect of a Continuous Subcutaneous
Infusion of Local Anesthetic Following Elective Surgery to the Great Toe.
AB - : Local anesthetic use for wound infusions, single injection, and continuous
nerve blocks for postoperative analgesia is well established. No study has
investigated the effect of a continuous block of the saphenous and superficial
peroneal nerves at the level of the ankle joint following first ray surgery. A
double blind randomized controlled trial was designed. One hundred patients with
hallux valgus and rigidus requiring surgical correction were recruited and
randomized to receive a postoperative continuous infusion at the ankle of normal
saline or ropivacaine for 24 hours. Pain scores were recorded on postoperative
days 1 and 7. There were more females than males. Follow-up was 100%. There were
no significant differences in demographic data between the 2 randomized groups.
There was no significant difference between the absolute visual analog scale
scores on day 1 (P = .14) and day 7 (P = .16); nor was there a significant
difference in reduction in scores between days 1 and 7 (P = .70). This study has
shown no benefit to postoperative analgesia with the use of a continuous infusion
of ropivacaine at the ankle. We, therefore, cannot currently recommend its use in
the way described. Further studies may still identify a role for continuous local
anesthetic infusions at the ankle to improve postoperative analgesia. LEVELS OF
EVIDENCE: Level I : Prospective randomised control trial.
PMID- 27613815
TI - Preoperative Anemia in Hindfoot and Ankle Arthrodesis.
AB - : This is a retrospective study (n = 39) evaluating the postoperative outcomes of
patients with mild to moderate preoperative anemia who underwent a hindfoot
and/or ankle arthrodesis. In the study, 32 patients did not have preoperative
anemia, and 7 had preoperative anemia. Mortality, length of hospital stay, blood
transfusions, deep-vein thrombosis, infection, time to union, malunion, delayed
union, nonunion, and ulceration were of particular interest. Comparative analyses
between patients with preoperative anemia and those without were performed
utilizing the independent samples t-test or by the nonparametric Mann-Whitney U
test. The Fisher exact test was used to analyze categorical data. The Shapiro
Wilk test was utilized to check normality. Statistical significance was defined
at a 2-sided level of P <.05. Delayed union, nonunion, and malunion were all
significantly increased in patients with preoperative anemia (P = .032, P = .004,
and P = .028, respectively). Accordingly, the median total number of
noninfectious complications (delayed union + nonunion + malunion) in patients
with preoperative anemia (0.86 +/- 0.38) was significantly higher than in
patients without preoperative anemia (0.063 +/- 0.25; P < .001). Patients with
preoperative anemia had a significantly longer length of hospital stay in days
(4.14 +/- 2.61). Total infection was also significantly associated with
preoperative anemia (P = .001). This study clearly demonstrated that infectious
complications, noninfectious complications, and length of hospital stay in
hindfoot and/or ankle arthrodesis was significantly affected by preoperative
anemia. Thus, consideration should be given to addressing preoperative anemia
prior to hindfoot and/or ankle arthrodesis. LEVELS OF EVIDENCE: Level II Study.
PMID- 27613816
TI - Arthroscopic Evaluation of Syndesmotic Instability and Malreduction.
AB - : Ankle fractures are a common injury treated by orthopaedic surgeons. The distal
tibiofibular syndesmosis can be injured during these fractures as well as in
isolation. They pose a significant challenge with regard to the diagnosis of
instability as well as evaluating reduction after fixation. Multiple studies have
demonstrated that traditional radiographic analysis fails to accurately identify
syndesmotic diastasis, instability, or malreduction. Ankle arthroscopy has been
proposed as an alternative way to evaluate the syndesmosis. Ten transtibial
amputation cadavers were utilized for this study. Two distinct analyses were
undertaken. The first, analysis of instability, utilized 2 dissection groups, a
superficial dissection only and a partial disruption instability model. The
second analysis was of syndesmotic malreduction. For this, all 10 specimens
underwent complete disruption of the syndesmosis and subsequent fixation in
either anatomic alignment or malreduction. Both analyses were performed by
surgeons blinded to the condition of the syndesmosis. Two groups of surgeons were
able to identify syndesmotic instability a combined 75% of the time. Malreduction
diagnosis was mixed with a 100% accurate diagnosis of sagittal plane displacement
but only 50% accuracy for rotation and 17% for an anatomic reduction. Syndesmotic
injury during ankle fracture presents a significant problem to the treating
surgeon. Ankle arthroscopy has been shown in the literature to be highly
sensitive for diagnosing instability but has not been evaluated in diagnosing
malreduction. The current study shows moderate success in diagnosing both
malreduction and instability. LEVELS OF EVIDENCE: Therapeutic, Level V: Basic
Science.
PMID- 27613817
TI - First Trimester Maternal Glycated Hemoglobin and Sex Hormone-Binding Globulin Do
Not Predict Third Trimester Glucose Intolerance of Pregnancy.
AB - Early pregnancy prediction of third trimester glucose intolerance may identify a
population of women whose trajectory toward gestational diabetes mellitus (GDM)
is modifiable. We assessed whether first trimester glycated hemoglobin (HbA1c)
and sex hormone-binding globulin (SHBG), markers of insulin resistance, predicted
third trimester glucose intolerance. Nondiabetic women with singleton pregnancies
enrolled in a prospective observational study, 11 0/7 to 14 6/7 weeks. At
enrollment, maternal characteristics, medical history, and blood samples were
collected for HbA1c and SHBG. Two-step GDM screening was performed, 22 0/7 to 33
6/7 weeks. A 50 g oral glucose tolerance test >=130 mg/dL defined screen
positive, or glucose intolerance. Carpenter-Coustan criteria diagnosed GDM. Means
HbA1c and SHBG were compared between glucose-intolerant versus normoglycemic
women, and GDM versus no GDM women. We report unadjusted and adjusted odds ratios
(OR; 95% confidence interval [CI]) of regression analyses. Adjusted models
include race, enrollment body mass index, and history of GDM. Among 250 women,
29% were glucose intolerant and 6% had GDM. Among glucose-intolerant women, HbA1c
was higher (5.3 +/- 0.3 vs. 5.1 +/- 0.3, P = .01) and associated with glucose
intolerance in unadjusted, but not adjusted, models (OR: 2.9, 95% CI: 1.2-7.1;
adjusted odds ratio [aOR]: 2.0, 95% CI: 0.7-5.4). Among GDM women, HbA1c was
higher (5.4 +/- 0.4 vs 5.2 +/- 0.3, P = .002) and SHBG was lower (228 +/- 72 vs
288 +/- 93 mmol/L, P = .02). The HbA1c predicted GDM in unadjusted (OR: 13.2, 95%
CI: 2.6-68.0) but not adjusted (aOR: 6.7, 95% CI: 0.8-55.2) models. Although
metabolic alterations may well precede third trimester glucose intolerance,
neither HbA1c of SHBG remained an independent predictor of glucose intolerance or
GDM in adjusted models.
PMID- 27613818
TI - Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary
Syndrome.
AB - This review aimed to focus on the recent progress of the understanding of the
role of phosphatidylinositol 3-kinase (PI3K) in polycystic ovary syndrome (PCOS).
In recent years, it has been increasingly recognized that PI3K plays an important
role in PCOS whose pathogenesis is unclear. However, research continues into
revealing the details of how PI3Ks are involved in developing PCOS. Previous
studies have shown that activation of the PI3K-protein kinase B (Akt) signaling
pathway has important effects on insulin resistance and endometrial cancer.
Knowledge of the action of PI3K in PCOS might provide valuable information to
further validate the pathogenesis of PCOS and suggest new methods of treatment.
PMID- 27613819
TI - MicroRNA-593-3p regulates insulin-promoted glucose consumption by targeting
Slc38a1 and CLIP3.
AB - Insulin plays an important role in the regulation of glucose metabolism. However,
the molecular mechanisms involved are not entirely clarified. In this context, we
found that miR-593-3p negatively regulates insulin-regulated glucose metabolism
in hepatocellular carcinoma HepG2 and Bel7402 cells. We then identified Slc38a1
and CLIP3 as novel targets of miR-593-3p. Further studies demonstrated that
Slc38a1 and CLIP3 mediate insulin-regulated glucose metabolism. Interestingly, we
also demonstrated that miR-593-3p expression was negatively associated with
Slc38a1 and CLIP3 expression in insulin-treated HepG2 cells, and insulin-induced
Slc38a1 and CLIP3 expression via downregulation of miR-593-3p. Taken together,
this study indicates that inhibition of miRNA-593-3p by insulin promotes glucose
metabolism through the regulation of Slc38a1 and CLIP3 expression, and provides a
new insight into the role and mechanism of insulin-induced glycolysis.
PMID- 27613820
TI - Effects of essential amino acids on lipid metabolism in mice and humans.
AB - Eight amino acids are considered essential for human nutrition, and three of
them, including leucine, isoleucine and valine, are called as branched-chain
amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA
for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study
was to investigate (1) whether dietary deficiency of the other five essential
amino acids (EAAs), including phenylalanine, threonine, tryptophan, methionine
and lysine, would produce similar effects and (2) whether an association between
serum AAs and obesity was observed in humans in Chinese Han population. Similar
to BCAAs deprivation, dietary deficiency of any of these five EAAs for 7 days
significantly reduced abdominal fat mass, which is likely caused by increased
energy expenditure. Expression of genes and proteins related to lipolysis,
however, were differentially regulated by different EAAs. These results suggest a
crucial role of EAAs deprivation on lipid metabolism in mice. Our human studies
revealed that levels of four EAAs (leucine, isoleucine, valine and phenylalanine)
were elevated in obese humans compared with those in lean controls in Chinese Han
population. Based on the results obtained from mice, we speculate that these four
EAAs might play important roles in human obesity.
PMID- 27613821
TI - Paternal Mitochondrial Transmission in Intra-Species Caenorhabditis briggsae
Hybrids.
AB - To study mitochondrial-nuclear genetic interactions in the nematode
Caenorhabditis briggsae, our three laboratories independently created 38 intra
species cytoplasmic-nuclear hybrid (cybrid) lines. Although the cross design
combines maternal mitotypes with paternal nuclear genotypes, eight lines (21%)
unexpectedly contained paternal mitotypes. All eight share in common ancestry of
one of two genetically related strains. This unexpected parallel observation of
paternal mitochondrial transmission, undesirable given our intent of creating
cybrids, provides a serendipitous experimental model and framework to study the
molecular and evolutionary basis of uniparental mitochondrial inheritance.
PMID- 27613822
TI - Circulating granulocyte lifespan in compensated alcohol-related cirrhosis: a
pilot study.
AB - Although granulocyte dysfunction is known to occur in cirrhosis, in vivo studies
of granulocyte lifespan have not previously been performed. The normal
circulating granulocyte survival half-time (G - t1/2), determined using indium
111 ((111)In)-radiolabeled granulocytes, is ~7 h. In this pilot study, we aimed
to measure the in vivo G - t1/2 in compensated alcohol-related cirrhosis.
Sequential venous blood samples were obtained in abstinent subjects with alcohol
related cirrhosis over 24 h post injection (PI) of minimally manipulated (111)In
radiolabeled autologous mixed leukocytes. Purified granulocytes were isolated
from each sample using a magnetic microbead-antibody technique positively
selecting for the marker CD15. Granulocyte-associated radioactivity was expressed
relative to peak activity, plotted over time, and G - t1/2 estimated from data up
to 12 h PI This was compared with normal neutrophil half-time (N - t1/2),
determined using a similar method specifically selecting neutrophils in healthy
controls at a collaborating center. Seven patients with cirrhosis (six male, aged
57.8 +/- 9.4 years, all Child-Pugh class A) and seven normal controls (three
male, 64.4 +/- 5.6 years) were studied. Peripheral blood neutrophil counts were
similar in both groups (4.6 (3.5 - 5.5) * 10(9)/L vs. 2.8 (2.7 - 4.4) * 10(9)/L,
respectively, P = 0.277). G - t1/2 in cirrhosis was significantly lower than N -
t1/2 in controls (2.7 +/- 0.5 h vs. 4.4 +/- 1.0 h, P = 0.007). Transient rises in
granulocyte and neutrophil-associated activities occurred in four patients from
each group, typically earlier in cirrhosis (4-6 h PI) than in controls (8-10 h),
suggesting recirculation of radiolabeled cells released from an unidentified
focus. Reduced in vivo granulocyte survival in compensated alcohol-related
cirrhosis is a novel finding and potentially another mechanism for immune
dysfunction in chronic liver disease. Larger studies are needed to corroborate
these pilot data and assess intravascular neutrophil residency in other disease
etiologies.
PMID- 27613823
TI - Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced
chronic ovine hypertension model.
AB - Hypertension is a major risk factor for many cardiovascular diseases and leads to
subsequent concomitant pathologies such as left ventricular hypertrophy (LVH).
Translational approaches using large animals get more important as they allow the
use of standard clinical procedures in an experimental setting. Therefore, the
aim of this study was to establish a minimally invasive ovine hypertension model
using chronic angiotensin II (ANG II) treatment and to characterize its effects
on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps
filled with either vehicle control (n = 7) or ANG II (n = 9) for 8 weeks. Mean
arterial blood pressure in the ANG II-treated group increased from 87.4 +/- 5.3
to 111.8 +/- 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging
showed an increase in left ventricular mass from 112 +/- 12.6 g to 131 +/- 18.7 g
after 7 weeks (P = 0.0017). This was confirmed by postmortem measurement of left
ventricular wall thickness which was higher in ANG II-treated animals compared to
the control group (18 +/- 4 mm vs. 13 +/- 2 mm, respectively, P = 0.002).
However, ANG II-treated sheep did not reveal any signs of fibrosis or
inflammatory infiltrates as defined by picrosirius red and H&E staining on
myocardial full thickness paraffin sections of both atria and ventricles.
Measurements of plasma high-sensitivity C-reactive protein and urinary 8-iso
prostaglandin F2alpha were inconspicuous in all animals. Furthermore,
multielectrode surface mapping of the heart did not show any differences in
epicardial conduction velocity and heterogeneity. These data demonstrate that
chronic ANG II treatment using osmotic minipumps presents a reliable, minimally
invasive approach to establish hypertension and nonfibrotic LVH in sheep.
PMID- 27613824
TI - Contributions of upper gut hormones and motility to the energy intake-suppressant
effects of intraduodenal nutrients in healthy, lean men - a pooled-data analysis.
AB - We have previously identified pyloric pressures and plasma cholecystokinin (CCK)
concentrations as independent determinants of energy intake following
administration of intraduodenal lipid and intravenous CCK. We evaluated in
healthy men whether these parameters also determine energy intake in response to
intraduodenal protein, and whether, across the nutrients, any predominant
gastrointestinal (GI) factors exist, or many factors make small contributions.
Data from nine published studies, in which antropyloroduodenal pressures, GI
hormones, and GI /appetite perceptions were measured during intraduodenal lipid
or protein infusions, were pooled. In all studies energy intake was quantified
immediately after the infusions. Specific variables for inclusion in a mixed
effects multivariable model for determination of independent predictors of energy
intake were chosen following assessment for collinearity, and within-subject
correlations between energy intake and these variables were determined using
bivariate analyses adjusted for repeated measures. In models based on all
studies, or lipid studies, there were significant effects for amplitude of antral
pressure waves, premeal glucagon-like peptide-1 (GLP-1) and time-to-peak GLP-1
concentrations, GLP-1 AUC and bloating scores (P < 0.05), and trends for basal
pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK
concentrations, and hunger and nausea scores (0.05 < P <= 0.094), to be
independent determinants of subsequent energy intake. In the model including the
protein studies, only BPP was identified as an independent determinant of energy
intake (P < 0.05). No single parameter was identified across all models, and
effects of the variables identified were relatively small. Taken together, while
GI mechanisms contribute to the regulation of acute energy intake by lipid and
protein, their contribution to the latter is much less. Moreover, the effects are
likely to reflect small, cumulative contributions from a range of interrelated
factors.
PMID- 27613826
TI - Long-Lasting Changes in Muscle Twitch Force During Simulated Work While Standing
or Walking.
AB - OBJECTIVE: The aim of this study was to evaluate the long-lasting effects of
prolonged standing work on a hard floor or floor mat and slow-pace walking on
muscle twitch force (MTF) elicited by electrical stimulation. BACKGROUND:
Prolonged standing work may alter lower-leg muscle function, which can be
quantified by changes in the MTF amplitude and duration related to muscle
fatigue. Ergonomic interventions have been proposed to mitigate fatigue and
discomfort; however, their influences remain controversial. METHOD: Ten men and
eight women simulated standing work in 320-min experiments with three conditions:
standing on a hard floor or an antifatigue mat and walking on a treadmill, each
including three seated rest breaks. MTF in the gastrocnemius-soleus muscles was
evaluated through changes in signal amplitude and duration. RESULTS: The
significant decrease of MTF amplitude and an increase of duration after standing
work on a hard floor and on a mat persisted beyond 1 hr postwork. During walking,
significant MTF metrics changes appeared 30 min postwork. MTF amplitude decrease
was not significant after the first 110 min in any of the conditions; however,
MTF duration was significantly higher than baseline in the standing conditions.
CONCLUSION: Similar long-lasting weakening of MTF was induced by standing on a
hard floor and on an antifatigue mat. However, walking partially attenuated this
phenomenon. APPLICATION: Mostly static standing is likely to contribute to
alterations of MTF in lower-leg muscles and potentially to musculoskeletal
disorders regardless of the flooring characteristics. Occupational activities
including slow-pace walking may reduce such deterioration in muscle function.
PMID- 27613825
TI - Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic
lipotoxicity in obese mice.
AB - Eukaryotic elongation factor EEF1A1 is induced by oxidative and ER stress, and
contributes to subsequent cell death in many cell types, including hepatocytes.
We recently showed that blocking the protein synthesis activity of EEF1A1 with
the peptide inhibitor, didemnin B, decreases saturated fatty acid overload
induced cell death in HepG2 cells. In light of this and other recent work
suggesting that limiting protein synthesis may be beneficial in treating ER
stress-related disease, we hypothesized that acute intervention with didemnin B
would decrease hepatic ER stress and lipotoxicity in obese mice with nonalcoholic
fatty liver disease (NAFLD). Hyperphagic male ob/ob mice were fed semipurified
diet for 4 weeks, and during week 5 received i.p. injections of didemnin B or
vehicle on days 1, 4, and 7. Interestingly, we observed that administration of
this compound modestly decreased food intake without evidence of illness or
distress, and thus included an additional control group matched for food
consumption with didemnin B-treated animals. Treatment with didemnin B improved
several characteristics of hepatic lipotoxicity to a greater extent than the
effects of caloric restriction alone, including hepatic steatosis, and some
hepatic markers of ER stress and inflammation (GRP78, Xbp1s, and Mcp1). Plasma
lipid and lipoprotein profiles and histopathological measures of NAFLD, including
lobular inflammation, and total NAFLD activity score were also improved by
didemnin B. These data indicate that acute intervention with the EEF1A inhibitor,
didemnin B, improves hepatic lipotoxicity in obese mice with NAFLD through
mechanisms not entirely dependent on decreased food intake, suggesting a
potential therapeutic strategy for this ER stress-related disease.
PMID- 27613827
TI - Hysteresis in Mental Workload and Task Performance: The Influence of Demand
Transitions and Task Prioritization.
AB - OBJECTIVE: We examine how transitions in task demand are manifested in mental
workload and performance in a dual-task setting. BACKGROUND: Hysteresis has been
defined as the ongoing influence of demand levels prior to a demand transition.
Authors of previous studies predominantly examined hysteretic effects in terms of
performance. However, little is known about the temporal development of
hysteresis in mental workload. METHOD: A simulated driving task was combined with
an auditory memory task. Participants were instructed to prioritize driving or to
prioritize both tasks equally. Three experimental conditions with low, high, and
low task demands were constructed by manipulating the frequency of lane changing.
Multiple measures of subjective mental workload were taken during experimental
conditions. RESULTS: Contrary to our prediction, no hysteretic effects were found
after the high- to low-demand transition. However, a hysteretic effect in mental
workload was found within the high-demand condition, which degraded toward the
end of the high condition. Priority instructions were not reflected in
performance. CONCLUSION: Online assessment of both performance and mental
workload demonstrates the transient nature of hysteretic effects. An explanation
for the observed hysteretic effect in mental workload is offered in terms of
effort regulation. APPLICATION: An informed arrival at the scene is important in
safety operations, but peaks in mental workload should be avoided to prevent
buildup of fatigue. Therefore, communication technologies should incorporate the
historical profile of task demand.
PMID- 27613828
TI - Human astrocytes secrete IL-6 to promote glioma migration and invasion through
upregulation of cytomembrane MMP14.
AB - The brain microenvironment has emerged as an important component in malignant
progression of human glioma. However, astrocytes, the most abundant glial cells
in the glioma microenvironment, have as yet a poorly defined role in the
development of this disease, particularly with regard to invasion. Here, we co
cultured human astrocytes with human glioma cell lines, U251 and A172, in an in
vitro transwell system in order to ascertain their influence on migration and
invasion of gliomas. mRNA and protein expression assays were subsequently used to
identify candidate proteins mediating this activity. Astrocytes significantly
increased migration and invasion of both U251 and A172 cells in migration and
invasion (plus matrigel) assays. Membrane type 1 matrix metalloproteinase (MMP14)
originating from glioma cells was identified in qRT-PCR as the most highly up
regulated member of the MMP family of genes (~ 3 fold, p < 0.05) in this system.
A cytokine array and ELISA were used to identify interleukin-6 (IL-6) as a highly
increased factor in media collected from astrocytes, especially under co-culture
conditions. IL-6 was also the key cytokine inducing cytomembrane MMP14
expression, the active form of MMP14, in glioma cells. Knockdown of MMP14 with
siRNA led to decreased migration and invasion. Taken together, our results
indicated that cytomembrane MMP14 was induced by IL-6 secreted from astrocytes,
thereby enhancing the migration and invasion of glioma cells through activation
of MMP2. Therefore, this IL-6 and MMP14 axis between astrocytes and glioma cells
may become a potential target for treatment of glioma patients.
PMID- 27613829
TI - Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA
regulatory network.
AB - Despite improvements in surgical procedures and chemotherapy, pancreatic cancer
remains one of the most aggressive and fatal human malignancies, with a low 5
year survival rate of only 8%. Therefore, novel strategies for prevention and
treatment are urgently needed. Here, we investigated the mechanisms underlying
the anti-pancreatic cancer effects dihydroartemisinin (DHA). Microarray and
systematic analysis showed that DHA suppressed proliferation, inhibited
angiogenesis and promoted apoptosis in two different human pancreatic cancer cell
lines, and that 5 DHA-regulated microRNAs and 11 of their target mRNAs were
involved in these effects via 19 microRNA-mRNA interactions. Four of these
microRNAs, 9 of the mRNAs and 17 of the interactions were experimentally
verified. Furthermore, we found that the anti-pancreatic caner effects of DHA in
vivo involved 4 microRNAs, 9 mRNAs and 17 microRNA-mRNA interactions. These
results improve the understanding of the mechanisms by which DHA suppresses
proliferation and angiogenesis and promotes apoptosis in pancreatic cancer cells
and indicate that DHA, an effective antimalarial drug, might improve pancreatic
cancer treatments.
PMID- 27613830
TI - Molecular differences between cerebral blood volume and vessel size in
glioblastoma multiforme.
AB - The purpose of this study was to investigate the molecular background of cerebral
blood volume (CBV) and vessel size (VS) of capillaries in glioblastoma multiforme
(GBM). Both parameters are derived from extended perfusion MR imaging.A
prospective case study including 21 patients (median age 66 years, 10 females)
was performed. Before operation, CBV and VS of contrast enhancing tumor were
assessed. Tissue was sampled from the assessed areas under neuronavigation
control. After RNA extraction, transcriptional data was analyzed by Weighted Gene
Co-Expression Network Analysis (WGCNA) and split into modules based on its
network affiliations. Gene Set Enrichment Analysis (GSEA) identified biological
functions or pathways of the genetic modules. These were applied on 484 GBM
samples of the TCGA database.Ten modules were highly correlated to CBV and VS.
One module was exclusively associated to VS and highly correlated to hypoxia,
another one exclusively to CBV showing strong enrichments in the Epithelial
Growth Factor (EGF) pathway and Epithelial-to-Mesenchymal-Transition (EMT).
Moreover, patients with increased CBV and VS predominantly showed a mesenchymal
gene-expression, a finding that could be corroborated by TCGA data.In conclusion,
CBV and VS mirror different genetic pathways and reflect certain molecular
subclasses of GBM.
PMID- 27613831
TI - Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the
Wnt/beta-catenin signaling pathway.
AB - CircRNA is a novel type of RNA molecule formed by a covalently closed loop which
have no 5'-3' polarity and possess no polyA tail and relatively stable due to the
cyclic structure. Therefore, they may serve as potential targets and diagnosis
biomarkers for tumor therapy. cZNF292 is an important circular oncogenic RNA and
plays a critical role in the progression of tube formation. This study is aimed
at exploring the role of cZNF292 in human glioma tube formation and its potential
mechanism of action. We found that cZNF292 silencing suppresses tube formation by
inhibiting glioma cell proliferation and cell cycle progression. Cell cycle
progression in human glioma U87MG and U251 cells was halted at S/G2/M phase via
the Wnt/beta-catenin signaling pathway and related genes such as PRR11, Cyclin A,
p-CDK2, VEGFR-1/2, p-VEGFR-1/2 and EGFR. The results suggest that cZNF292
silencing plays an important role in the tube formation process and has potential
for application as a therapeutic target and biomarker in glioma.
PMID- 27613832
TI - Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell
carcinoma cells via suppressing epithelial-mesenchymal transition.
AB - Long non-coding RNAs (lncRNAs) have emerged recently as key regulators of tumor
development and progression. Our previous study identified an NF-KappaB
interacting lncRNA (NKILA) which was negatively correlated with breast cancer
metastasis and patient prognosis. However, its clinical significance and
potential role in Tongue squamous cell carcinoma (TSCC) remain unclear. Here we
show that NKILA is down-regulated in TSCC cancer tissues than that in matched
adjacent noncancerous tissues. And low NKILA expression in TSCC is significantly
correlated with tumor metastasis and poor patient prognosis. In vitro,
overexpression of NKILA decreases TSCC cells migration and invasion. Mechanistic
study shows that NKILA inhibits the phosphorylation of IkappaBalpha and NF-kappaB
activation as well as the induction of the epithelial-mesenchymal transition
(EMT) process. Ectopic expression of NKILA in Tscca cells inhibits NF-kappaB
activator TNF-alpha-promoted cell migration and invasion, while applying NF
kappaB inhibitor Bay-117082 or JSH-23 in NKILA silenced CAL27 cells reverses cell
migration capacity to lower level. In vivo experimental metastasis model also
demonstrates NKILA inhibits lung metastasis of NOD/SCID mice with TSCC tumors.
These results suggested that NKILA is a vital determinant of TSCC migration and
invasion and NF-kappaB signaling pathway mediates this effect. Given the above
mentioned function of NKILA, it could act as a potential predictor for overall
survival in patients with TSCC and a potential therapeutic target for TSCC
intervention.
PMID- 27613833
TI - Diacetoxyscirpenol as a new anticancer agent to target hypoxia-inducible factor
1.
AB - Hypoxia activates hypoxia-inducible factor 1, which promotes the progression of
malignancy by stimulating angiogenesis and by augmenting the ability of tumors to
survive. Thus, HIF-1 is one of the most compelling targets for treating cancers.
The aim of this study was to find a small molecule that inhibits HIF-1 under
hypoxia in cancer cells. 7,280 compounds in a chemical library were tested in a
cancer cell line expressing luciferase HIF-dependently. Through three rounds of
screening, we finally picked up a compound that originates from a marine
bacterium parasitizing red alga. The antibiotic potently inhibited HIF-1
expression and its transcriptional activity in cancer cells exposed to hypoxia.
Through two-step fractionation, diacetoxyscirpenol was purified and identified as
a HIF-inhibiting ingredient. Mechanistically, diacetoxyscirpenol inhibits the
synthesis of HIF-1alpha protein and also interferes with the dimerization of HIF
1alpha and ARNT. It attenuates HIF-mediated gene expression in cancer cells
exposed to hypoxia, and by doing so reduces tumorigenic and angiogenic potentials
of cancer cells. More importantly, diacetoxyscirpenol retarded tumor growth in
mice, and reduced HIF-1alpha expression and vascular formation in the tumors.
Overall, diacetoxyscirpenol is considered a potential drug deregulating the HIF-1
signaling pathway, and it could be beneficially employed for treating malignant
tumors with hypoxic microenvironment.
PMID- 27613834
TI - Generation and molecular characterization of pancreatic cancer patient-derived
xenografts reveals their heterologous nature.
AB - Pancreatic ductal adenocarcinoma (PDAC) is the most challenging type of cancer to
treat, with a 5-year survival rate of <10%. Furthermore, because of the large
portion of the inoperable cases, it is difficult to obtain specimens to study the
biology of the tumors. Therefore, a patient-derived xenograft (PDX) model is an
attractive option for preserving and expanding these tumors for translational
research. Here we report the generation and characterization of 20 PDX models of
PDAC. The success rate of the initial graft was 74% and most tumors were re
transplantable. Histological analysis of the PDXs and primary tumors revealed a
conserved expression pattern of p53 and SMAD4; an exome single nucleotide
polymorphism (SNP) array and Comprehensive Cancer Panel showed that PDXs retained
over 94% of cancer-associated variants. In addition, Polyphen2 and the Sorting
Intolerant from Tolerant (SIFT) prediction identified 623 variants among the
functional SNPs, highlighting the heterologous nature of pancreatic PDXs; an
analysis of 409 tumor suppressor genes and oncogenes in Comprehensive Cancer
Panel revealed heterologous cancer gene mutation profiles for each PDX-primary
tumor pair. Altogether, we expect these PDX models are a promising platform for
screening novel therapeutic agents and diagnostic markers for the detection and
eradication of PDAC.
PMID- 27613835
TI - Mechanism of suppressors of cytokine signaling 1 inhibition of epithelial
mesenchymal transition signaling through ROS regulation in colon cancer cells:
suppression of Src leading to thioredoxin up-regulation.
AB - Reactive oxygen species (ROS) participate in malignant progression of cancers
including epithelial-mesenchymal transition (EMT). We have investigated the role
of suppressors of cytokine signaling (SOCS)1 as an inhibitor of ROS-induced EMT
using colon cancer cell lines transduced with SOCS1 and shSOCS1. Hydrogen
peroxide treatment induced EMT features such as elevation of vimentin and Snail
with a corresponding reduction of E-cadherin. The EMT markers are significantly
decreased upon SOCS1 over-expression while increased under SOCS1 knock-down.
SOCS1 inhibited ROS signaling pathways associated with EMT such as Src, Jak, and
p65. Of note, strong up-regulation of Src activity in SOCS1-ablated cells was
responsible for the elevated signaling leading to EMT, as shSrc or Src inhibitor
abolished the shSOCS1-induced promotion of EMT response. Suppression of ROS
inducible EMT markers and invasion in SOCS1 over-expressing cells correlated with
significantly low intracellular ROS levels in these cells. Analysis of
antioxidant enzymes in SOCS1-transduced cells revealed a selective up-regulation
of thioredoxin (Trx1), while thioredoxin ablation restored ROS levels and the
associated EMT markers. As a mechanism of thioredoxin up-regulation by SOCS1,
inhibition of Src activity promoting nuclear translocation of Nrf-2 is proposed.
Taken together, our data strongly indicate that SOCS1 antagonizes EMT by
suppressing Src activity, leading to thioredoxin expression and down-regulation
of ROS levels in colon cancer cells.
PMID- 27613836
TI - The novel compound STK405759 is a microtubule-targeting agent with potent and
selective cytotoxicity against multiple myeloma in vitro and in vivo.
AB - Despite advances in treatment, multiple myeloma (MM) remains incurable. Here we
propose the use of STK405759, a novel microtubule targeting agent (MTA) and
member of the furan metotica family for MM therapy.STK405759 inhibited tubulin
polymerization in a cell-free system and in myeloma cells. This molecule had
potent cytotoxic activity against several MM cell lines and patient-derived MM
cells. Moreover, STK405759 demonstrated cytotoxicity against drug-resistant
myeloma cells that overexpressed the P-glycoprotein drug-efflux pump. STK405759
was not cytotoxic to peripheral blood mononuclear cells, including activated B
and T lymphocytes. This compound caused mitotic arrest and apoptosis of myeloma
cells characterized by cleavage of poly (ADP-ribose) polymerase-1 and caspase-8,
as well as decreased protein expression of mcl-1. The combination of STK405759
with bortezomib, lenalidomide or dexamethasone had synergistic cytotoxic
activity. In in vivo studies, STK405759-treated mice had significantly decreased
MM tumor burden and prolonged survival compared to vehicle treated- mice.These
results provide a rationale for further evaluation of STK405759 as monotherapy or
part of combination therapy for treating patients with MM.
PMID- 27613837
TI - Expression/activation of alpha5beta1 integrin is linked to the beta-catenin
signaling pathway to drive migration in glioma cells.
AB - The Wnt/beta catenin pathway has been highlighted as an important player of brain
tumors aggressiveness and resistance to therapies. Increasing knowledges of the
regulation of beta-catenin transactivation point out its hub position in
different pathophysiological outcomes in glioma such as survival and migration.
Crosstalks between integrins and beta-catenin pathways have been suggested in
several tumor tissues. As we demonstrated earlier that alpha5beta1 integrin may
be considered as a therapeutic target in high grade glioma through its
contribution to glioma cell migration and resistance to chemotherapy, we
addressed here the potential relationship between alpha5beta1 integrin and beta
catenin activation in glioma cells. We demonstrated that overexpression and
activation by fibronectin of alpha5beta1 integrin allowed the transactivation of
beta-catenin gene targets included in an EMT-like program that induced an
increase in cell migration. Hampering of beta catenin activation and cell
migration could be similarly achieved by a specific integrin antagonist. In
addition we showed that alpha5beta1 integrin/AKT axis is mainly involved in these
processes. However, blockade of beta-catenin by XAV939 (tankyrase inhibitor
leading to beta-catenin degradation) did not synergize with p53 activation aiming
to cell apoptosis as was the case with integrin antagonists. We therefore propose
a dual implication of alpha5beta1 integrin/AKT axis in glioma cell resistance to
therapies and migration each supported by different signaling pathways. Our data
thus suggest that alpha5beta1 integrin may be added to the growing list of beta
catenin modulators and provide new evidences to assign this integrin as a
valuable target to fight high grade glioma.
PMID- 27613838
TI - Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like
properties and resistance to chemotherapy.
AB - NumbL, or Numb-like, is a close homologue of Numb, and is part of an evolutionary
conserved protein family implicated in some important cellular processes. Numb is
a protein involved in cell development, in cell adhesion and migration, in
asymmetric cell division, and in targeting proteins for endocytosis and
ubiquitination. NumbL exhibits some overlapping functions with Numb, but its role
in tumorigenesis is not fully known. Here we showed that the downregulation of
NumbL alone is sufficient to increase NICD nuclear translocation and induce Notch
pathway activation. Furthermore, NumbL downregulation increases epithelial
mesenchymal transition (EMT) and cancer stem cell (CSC)-related gene transcripts
and CSC-like phenotypes, including an increase in the CSC-like pool. These data
suggest that NumbL can act independently as a tumor suppressor gene. Furthermore,
an absence of NumbL induces chemoresistance in tumor cells. An analysis of human
tumors indicates that NumbL is downregulated in a variable percentage of human
tumors, with lower levels of this gene correlated with worse prognosis in colon,
breast and lung tumors. Therefore, NumbL can act as an independent tumor
suppressor inhibiting the Notch pathway and regulating the cancer stem cell pool.
PMID- 27613839
TI - Immune inflammation indicators and implication for immune modulation strategies
in advanced hepatocellular carcinoma patients receiving sorafenib.
AB - We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte
ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their
prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated
with sorafenib. 56 advanced HCC patients receiving sorafenib were available for
our analysis. Lymphocyte, neutrophil and platelet were measured before beginning
of treatment and after one month. Patient with SII >= 360 showed lower median PFS
(2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with
respect to patients with SII < 360.NLR >= 3 had a lower median PFS (2.6 vs. 3.3
months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with
NLR < 3. After adjusting for clinical covariates SII and NLR remained an
independent prognostic factor for OS. The SII and NLR represent potential
prognostic indicator in patients with advanced HCC treated with sorafenib.
PMID- 27613840
TI - Comparative profiling between primary colorectal carcinomas and metastases
identifies heterogeneity on drug resistance.
AB - Metastases cause recurrence and mortality for patients with colorectal carcinomas
(CRC). In present study, we evaluated heterogeneity on drug resistance and its
underlying mechanism between metastatic and primary CRC. Immunohistochemical
results from clinical tissue microarray (TMA) suggested that the expression
concordance rates of cancer stem cells (CSCs) and drug resistance relative
proteins between lymph-node metastatic and primary CRC foci were low. The
apoptotic and proliferation indexes in metastasis CRC specimens were decreased
compared with primary. In vitro experimental results indicated that the migration
and invasion abilities were upregulated in metastatic cells SW620 compared with
primary cells SW480, the cellular efflux ability and WNT/beta-catenin activity
were also upregulated in SW620 cells. After 5-fluorouracil (5-Fu) treatment, the
reduction in the proportion of cell apoptosis, CD133 and TERT expression levels
in SW620 were lower than that in SW480 cells. Bioinformatics analysis in whole
genome transcriptional profiling results between metastatic and primary CRC cells
suggested that differentially expressed genes were mainly centered on well
characterized signaling pathways including WNT/beta-catenin, cell cycle and cell
junction. Collectively, heterogeneity of drug resistant was present between
metastatic and primary CRC specimens and cell lines, the abnormal activation of
WNT/beta-catenin signaling pathway could be a potential molecular leading to drug
resistant ability enhancing in metastatic CRC cells.
PMID- 27613841
TI - Common genetic variations in cell cycle and DNA repair pathways associated with
pediatric brain tumor susceptibility.
AB - Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain
tumors (PBTs) is limited. Therefore, we investigated the association between
single nucleotide polymorphisms (SNPs), identified by candidate gene-association
studies on adult brain tumors, and PBT risk.The study is based on the largest
series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7
19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were
analyzed using unconditional logistic regression.The results showed EGFRrs730437
and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986
may increase risk of these tumors. Moreover, stratified analyses indicated
CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased
risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma
subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and
GLTSCRrs1035938 as well as a decreased risk of this subtype associated with
XRCC4rs7721416 and XRCC4rs2662242 were detected.This study indicates SNPs in
EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with
the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations
associated with susceptibility to adult brain tumors also seem to be associated
with PBT risk, suggesting pediatric and adult brain tumors might share similar
etiological pathways.
PMID- 27613842
TI - Methylation and expression of PTPN22 in esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma (ESCC) is a fatal disease contributed by both
genetic and epigenetic factors. The epigenetic alteration of protein tyrosine
phosphatase non-receptor type 22 (PTPN22) and its clinical significance in ESCC
were still not yet clarified. A quantitative methylation study of PTPN22 and its
expression were conducted in 121 and 31 paired tumor and adjacent normal tissue
(ANT), respectively. Moreover, the association between PTPN22 methylation and
clinicopathological parameters was evaluated. We found that the methylation level
of PTPN22 was significantly elevated in tumor tissues (66.3%) relative to ANT
(62.1%) (p=0.005). The methylation level of non-smoking ANT (59.1%) was
significant lower than smoking ESCC tissue (65.8%) (p=0.03); similarly, the
methylation levels in ANT with no lymph node invasion (57.6%) were significant
lower than tumor tissues with lymph node invasion (67.5%) (p=0.001). PTPN22
expression in ESCC was lower than normal tissues, however the difference was not
statistically significant (p=0.55). Lower expression was more frequently occurred
in N1-3 and III stage patients, while higher expression was more likely to occur
in N0 and I-II stage patients. Lower expression of PTPN22 was associated with
poor overall survival (p=0.04). Taken together, PTPN22 was hypermethylationed in
ESCC. Hypermethylation was associated with lymph node invasion. The PTPN22
expression may act as a prognostic biomarker to identify patients at risk of high
grade.
PMID- 27613844
TI - NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung
cancer.
AB - Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor type
that is typically metastatic upon diagnosis. We have a poor understanding of the
factors that control SCLC progression and metastasis. TheNFIB transcription
factor is frequently amplified in mouse models of SCLC, but clear evidence that
NFIB promotes SCLC in vivo is lacking. We report that in mouse models, Nfib
amplifications are far more frequent in liver metastases over primary SCLC,
suggesting roles in tumor progression/metastasis. Overexpression of Nfib in a
sensitized mouse model led to acceleration of SCLC, indicating that Nfib
functions as a bona fide oncogene. Suppression of Nfib expression in cell lines
derived from the doxycycline-inducible Rb/p53/TET-Nfib model led to increased
apoptosis and suppression of proliferation. Transcriptional analysis revealed
that Nfib regulates the expression of genes related to axon guidance, focal
adhesion and extracellular matrix-receptor interactions. These data indicate that
Nfib is a potent oncogene in SCLC, and the enrichment of Nfib amplifications in
liver metastases over primary SCLC points to Nfib as a candidate driver of SCLC
metastasis.
PMID- 27613843
TI - Metabolic flux-driven sialylation alters internalization, recycling, and drug
sensitivity of the epidermal growth factor receptor (EGFR) in SW1990 pancreatic
cancer cells.
AB - In prior work we reported that advanced stage, drug-resistant pancreatic cancer
cells (the SW1990 line) can be sensitized to the EGFR-targeting tyrosine kinase
inhibitors (TKIs) erlotinib and gefitinib by treatment with 1,3,4-O-Bu3ManNAc
(Bioorg. Med. Chem. Lett. (2015) 25(6):1223-7). Here we provide mechanistic
insights into how this compound inhibits EGFR activity and provides synergy with
TKI drugs. First, we showed that the sialylation of the EGFR receptor was at most
only modestly enhanced (by ~20 to 30%) compared to overall ~2-fold increase in
cell surface levels of this sugar. Second, flux-driven sialylation did not alter
EGFR dimerization as has been reported for cancer cell lines that experience
increased sialylation due to spontaneous mutations. Instead, we present evidence
that 1,3,4-O-Bu3ManNAc treatment weakens the galectin lattice, increases the
internalization of EGFR, and shifts endosomal trafficking towards non-clathrin
mediated (NCM) endocytosis. Finally, by evaluating downstream targets of EGFR
signaling, we linked synergy between 1,3,4-O-Bu3ManNAc and existing TKI drugs to
a shift from clathrin-coated endocytosis (which allows EGFR signaling to continue
after internalization) towards NCM endocytosis, which targets internalized
moieties for degradation and thereby rapidly diminishes signaling.
PMID- 27613845
TI - A novel polymer-free ciglitazone-coated vascular stent: in vivo and ex vivo
analysis of stent endothelialization in a rabbit iliac artery model.
AB - AIM: Peroxisome proliferator-activated receptor-gamma (PPARg) agonists have known
pleiotropic cardiovascular effects with favourable properties in vascular
remodeling, and specifically in suppression of vascular smooth muscle cell
proliferation. A novel vascular stent coating using the PPARg ligand ciglitazone
(CCS) was investigated regarding its effects on endothelialization after 7 and 28
days. METHODS: Microporous bare metal stents (BMS) were coated with ciglitazone
by ultrasonic flux with a load of 255 MUg ciglitazone/stent. SixteenNew Zealand
white rabbits, fed a with high cholesterol diet, underwent stent implantation in
both iliac arteries. Everolimus-eluting stents (EES) and BMS were comparators.
Histology (CD 31 immunostaining, confocal and scanning electron microscopy,
morphometry) was performed after 7 and 28 days and by OCT (optical coherence
tomography) in vivo after 28 days. RESULTS: Microscopy showed comparable results
with near complete endothelialization in CCS and BMS (%CD31 above stent struts
after 7 days: 67.92+/-36.35 vs. 84.48+/-23.86; p = 0.55; endothel % above stent
struts: 77.22+/-27.9 vs. 83.89+/-27.91; p = 0.78). EES were less endothelialized
with minimal fibrin deposition, not found in BMS and CCS (% CD 31 above struts
after 28 days, BMS: 100.0+/-0.0 vs. EES: 95.9+/-3.57 vs. CCS: 100.0+/-0.0; p =
0.0292). OCT revealed no uncovered struts in all stents after 28 days.
CONCLUSIONS: Polymer-free coating with ciglitazone, a PPARg agonist is feasible
and stable over time. Our data prove unimpaired endothelial coverage of a
ciglitazone-coated vascular stent system by histology and OCT. Thus, this PPARg
agonist coating deserves further investigation to evaluate its potency on local
neointimal suppression.
PMID- 27613846
TI - Loss of prolyl hydroxylase domain protein 2 in vascular endothelium increases
pericyte coverage and promotes pulmonary arterial remodeling.
AB - Pulmonary arterial hypertension (PAH) is a leading cause of heart failure.
Although pulmonary endothelial dysfunction plays a crucial role in the
progression of the PAH, the underlying mechanisms are poorly understood. The HIF
alpha hydroxylase system is a key player in the regulation of vascular
remodeling. Knockout of HIF-2alpha has been reported to cause pulmonary
hypertension. The present study examined the role of endothelial cell specific
prolyl hydroxylase-2 (PHD2) in the development of PAH and pulmonary vascular
remodeling. The PHD2f/f mouse was crossbred with VE-Cadherin-Cre promoter mouse
to generate an endothelial specific PHD2 knockout (Cdh5-Cre-PHD2ECKO) mouse.
Pulmonary arterial pressure and the size of the right ventricle was significantly
elevated in the PHD2ECKO mice relative to the PHD2f/f controls. Knockout of PHD2
in EC was associated with vascular remodeling, as evidenced by an increase in
pulmonary arterial media to lumen ratio and number of muscularized arterioles.
The pericyte coverage and vascular smooth muscle cells were also significantly
increased in the PA. The increase in vascular pericytes was associated with
elevated expression of fibroblast specific protein-1 (FSP-1). Moreover,
perivascular interstitial fibrosis of pulmonary arteries was significantly
increased in the PHD2ECKO mice. Mechanistically, knockout of PHD2 in EC increased
the expression of Notch3 and transforming growth factor (TGF-beta) in the lung
tissue. We conclude that the expression of PHD2 in endothelial cells plays a
critical role in preventing pulmonary arterial remodeling in mice. Increased
Notch3/TGF-beta signaling and excessive pericyte coverage may be contributing to
the development of PAH following deletion of endothelial PHD2.
PMID- 27613848
TI - Repetitive transcranial magnetic stimulation (rTMS) improves behavioral and
biochemical deficits in levodopa-induced dyskinetic rats model.
AB - Fluctuations of dopamine levels and upregulations of NR2B tyrosine
phosphorylation in the striatum have been connected with levodopa (L-dopa)
induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial
magnetic stimulation (rTMS) is one of the noninvasive and potential method
treating dyskinesia. Yet, the effect of rTMS on the above key pathological events
remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22
days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and
subsequently applied rTMS daily for 3 weeks to LID rats model. The effect of rTMS
on abnormal involuntary movements (AIMs) was assessed. After ending the
experiments, we further determined tyrosine hydroxylase (TH)-positive
dopaminergic neurons number by immunohistochemistry, dopamine levels by HPLC,
glial cell line-derived neurotrophic factor (GDNF) levels by ELISA, NR2B tyrosine
phosphorylation and interactions of NR2B with Fyn by immunoblotting and
immunoprecipitation. The results demonstrated that rTMS obviously attenuated AIMs
scores, reduced the loss of nigral dopaminergic neurons and the fluctuations of
striatal dopamine levels. Meanwhile, rTMS significantly increased the expression
of GDNF, which couldrestore the damage of dopaminergic neurons. Additionally,
rTMS also reduced the levels of the NR2B tyrosine phosphorylation andits
interactions with Fyn in the lesioned striatum of LID rats model. Thus, these
data indicate that rTMS can provide benefit for the therapy of LID by improving
the key biochemical deficits related to dyskinesia.
PMID- 27613849
TI - Dentists' experiences of dentally anxious patients in a specialist setting: An
interpretative phenomenological analysis.
AB - Since dentists play an important role in the emergence and maintenance of dental
anxiety in patients, it is imperative to understand how dentists themselves
evaluate their work with anxious patients and how they perceive their
environment. Semi-structured interviews explored the working lives of six
dentists. Interpretative phenomenological analysis revealed four superordinate
themes: Negotiating identities, Control, Perceptions of dentistry and being a
dentist and Stress related to treating dentally anxious patients. Warranting
investigation in other settings, specialist dentists experienced conflicts
between being a helper and inflictor of pain, as well as dealing with conflicting
views concerning their status as a dentist.
PMID- 27613847
TI - Expression and regulation of immune-modulatory enzyme indoleamine 2,3-dioxygenase
(IDO) by human airway epithelial cells and its effect on T cell activation.
AB - Indoleamine 2,3-dioxygenase (IDO) catalyzes the degradation of tryptophan, which
plays a critical role in immune suppression through regulating the production of
a series of metabolites that are generally referred to as kynurenines. It has
become increasingly clear that epithelial cells (ECs) play an active role in
maintaining lung homeostasis by modulating the function of immune cells via
producing cytokines, chemokines, and anti-microbial mediators. In this study we
assessed the regulation of IDO activity and expression in human primary ECs and
EC lines under steady state conditions and in response to bacterial and
allergenic stimuli. We also investigated the potential immune modulatory
functions of IDO expression in human airway ECs. Our data clearly show that
airway ECs produce IDO, which is down-regulated in response to allergens and TLR
ligands while up-regulated in response to IFN-gamma. Using gene silencing, we
further demonstrate that IDO plays a key role in the EC-mediated suppression of
antigen-specific and polyclonal proliferation of T cells. Interestingly, our data
also show that ECs lose their inhibitory effect on T cell activation in response
to different TLR agonists mimicking bacterial or viral infections. In conclusion,
our work provides an understanding of how IDO is regulated in ECs as well as
demonstrates that "resting" ECs can suppress T cell activation in an IDO
dependent manner. These data provide new insight into how ECs, through the
production of IDO, can influence downstream innate and adaptive responses as part
of their function in maintaining immune homeostasis in the airways.
PMID- 27613850
TI - TWS1, a Novel Small Protein, Regulates Various Aspects of Seed and Plant
Development.
AB - Small proteins have long been overlooked due to their poor annotation and the
experimental challenges they pose. However, in recent years, their role in
various processes has started to emerge, opening new research avenues. Here, we
present the isolation and characterization of two allelic mutants, twisted seed1
1 (tws1-1) and tws1-2, which exhibit an array of developmental and biochemical
phenotypes in Arabidopsis (Arabidopsis thaliana) seeds. We have identified
AT5G01075 as the subtending gene encoding a small protein of 81 amino acids
localized in the endoplasmic reticulum. TWS1 is strongly expressed in seeds,
where it regulates both embryo development and accumulation of storage compounds.
TWS1 loss-of-function seeds exhibit increased starch, sucrose, and protein
accumulation at the detriment of fatty acids. TWS1 is also expressed in
vegetative and reproductive tissues, where it is responsible for proper epidermal
cell morphology and overall plant growth. At the cellular level, TWS1 is
responsible for cuticle deposition on epidermal cells and organization of the
endomembrane system. Finally, we show that TWS1 is a single-copy gene in
Arabidopsis, and it is specifically conserved among angiosperms.
PMID- 27613851
TI - The Proteasome Acts as a Hub for Plant Immunity and Is Targeted by Pseudomonas
Type III Effectors.
AB - Recent evidence suggests that the ubiquitin-proteasome system is involved in
several aspects of plant immunity and that a range of plant pathogens subvert the
ubiquitin-proteasome system to enhance their virulence. Here, we show that
proteasome activity is strongly induced during basal defense in Arabidopsis
(Arabidopsis thaliana). Mutant lines of the proteasome subunits RPT2a and RPN12a
support increased bacterial growth of virulent Pseudomonas syringae pv tomato
DC3000 (Pst) and Pseudomonas syringae pv maculicola ES4326. Both proteasome
subunits are required for pathogen-associated molecular pattern-triggered
immunity responses. Analysis of bacterial growth after a secondary infection of
systemic leaves revealed that the establishment of systemic acquired resistance
(SAR) is impaired in proteasome mutants, suggesting that the proteasome also
plays an important role in defense priming and SAR In addition, we show that Pst
inhibits proteasome activity in a type III secretion-dependent manner. A screen
for type III effector proteins from Pst for their ability to interfere with
proteasome activity revealed HopM1, HopAO1, HopA1, and HopG1 as putative
proteasome inhibitors. Biochemical characterization of HopM1 by mass spectrometry
indicates that HopM1 interacts with several E3 ubiquitin ligases and proteasome
subunits. This supports the hypothesis that HopM1 associates with the proteasome,
leading to its inhibition. Thus, the proteasome is an essential component of
pathogen-associated molecular pattern-triggered immunity and SAR, which is
targeted by multiple bacterial effectors.
PMID- 27613852
TI - Evidence for Hydraulic Vulnerability Segmentation and Lack of Xylem Refilling
under Tension.
AB - The vascular system of grapevine (Vitis spp.) has been reported as being highly
vulnerable, even though grapevine regularly experiences seasonal drought.
Consequently, stomata would remain open below water potentials that would
generate a high loss of stem hydraulic conductivity via xylem embolism. This
situation would necessitate daily cycles of embolism repair to restore hydraulic
function. However, a more parsimonious explanation is that some hydraulic
techniques are prone to artifacts in species with long vessels, leading to the
overestimation of vulnerability. The aim of this study was to provide an unbiased
assessment of (1) the vulnerability to drought-induced embolism in perennial and
annual organs and (2) the ability to refill embolized vessels in two Vitis
species X-ray micro-computed tomography observations of intact plants indicated
that both Vitis vinifera and Vitis riparia were relatively vulnerable, with the
pressure inducing 50% loss of stem hydraulic conductivity = -1.7 and -1.3 MPa,
respectively. In V. vinifera, both the stem and petiole had similar sigmoidal
vulnerability curves but differed in pressure inducing 50% loss of hydraulic
conductivity (-1.7 and -1 MPa for stem and petiole, respectively). Refilling was
not observed as long as bulk xylem pressure remained negative (e.g. at the apical
part of the plants; -0.11 +/- 0.02 MPa) and change in percentage loss of
conductivity was 0.02% +/- 0.01%. However, positive xylem pressure was observed
at the basal part of the plant (0.04 +/- 0.01 MPa), leading to a recovery of
conductance (change in percentage loss of conductivity = -0.24% +/- 0.12%). Our
findings provide evidence that grapevine is unable to repair embolized xylem
vessels under negative pressure, but its hydraulic vulnerability segmentation
provides significant protection of the perennial stem.
PMID- 27613853
TI - Oxidation of P700 in Photosystem I Is Essential for the Growth of Cyanobacteria.
AB - The photoinhibition of photosystem I (PSI) is lethal to oxygenic phototrophs.
Nevertheless, it is unclear how photodamage occurs or how oxygenic phototrophs
prevent it. Here, we provide evidence that keeping P700 (the reaction center
chlorophyll in PSI) oxidized protects PSI. Previous studies have suggested that
PSI photoinhibition does not occur in the two model cyanobacteria, Synechocystis
sp. PCC 6803 and Synechococcus elongatus PCC 7942, when photosynthetic CO2
fixation was suppressed under low CO2 partial pressure even in mutants deficient
in flavodiiron protein (FLV), which mediates alternative electron flow. The lack
of FLV in Synechococcus sp. PCC 7002 (S. 7002), however, is linked directly to
reduced growth and PSI photodamage under CO2-limiting conditions. Unlike
Synechocystis sp. PCC 6803 and S. elongatus PCC 7942, S. 7002 reduced P700 during
CO2-limited illumination in the absence of FLV, resulting in decreases in both
PSI and photosynthetic activities. Even at normal air CO2 concentration, the
growth of S. 7002 mutant was retarded relative to that of the wild type.
Therefore, P700 oxidation is essential for protecting PSI against
photoinhibition. Here, we present various strategies to alleviate PSI
photoinhibition in cyanobacteria.
PMID- 27613855
TI - The effect of maternal canthaxanthin supplementation and hen age on breeder
performance, early chick traits, and indices of innate immune function.
AB - Hen age and nutrition influence chick innate immunity. The immunomodulatory
antioxidant carotenoid canthaxanthin is transferred from the hen diet to the egg.
Antioxidants could protect the chick from bactericidal oxidative species produced
by the immune system. Broiler breeder hen diets were supplemented with 0
(Control), 6 (Low), or 12 (High) mg/kg canthaxanthin. Chick early growth and ex
vivo innate immunity were measured at 31 to 33 (Early), 45 to 47 (Mid), and 57 to
59 (Late) wk of hen age. Escherichia coli (E. coli) bactericidal capacity,
phagocyte activation (number of phagocytes containing at least one E. coli),
phagocytic capacity (number of phagocytes containing one or more E. coli), and
oxidative burst at 1 and 4 d of age were determined. Egg and chick liver
canthaxanthin and chick plasma total antioxidant capacity were measured.
Differences were considered significant at P <= 0.05. Breeder productivity was
greatest for the Low hens; diet did not affect egg yolk, albumen, or shell
proportions. Egg canthaxanthin increased with maternal supplementation and
plateaued after 28 days, but was not affected by hen age. Chick liver
canthaxanthin increased with maternal supplementation, but decreased as hens
aged. Hen diet did not affect broiler chick performance to 21 days of age.
Maternal canthaxanthin at 6 mg/kg increased chick E. coli bactericidal capacity
and d 1 oxidative burst; phagocytosis was unaffected. E. coli bactericidal
capacity decreased as hens aged, but increased from 1 to 4 d, indicating
maturation of chick innate immunity. Plasma total antioxidant capacity at d 1
increased with maternal canthaxanthin in chicks from Mid and Late hens.
Canthaxanthin possesses immuno-modulatory and antioxidant properties, and hen age
affected chick innate immune development. Single-comb White Leghorn hens were fed
the same levels of canthaxanthin to determine the rate of incorporation into
eggs. Egg canthaxanthin reached a plateau after 7 d. Canthaxanthin in the hen
diet at 6 mg/kg resulted in the greatest positive effect on hen performance, with
little effect on the chick.
PMID- 27613857
TI - Hydrophobic ice-binding sites confer hyperactivity of an antifreeze protein from
a snow mold fungus.
AB - Snow mold fungus, Typhula ishikariensis, secretes seven antifreeze protein
isoforms (denoted TisAFPs) that assist in the survival of the mold under snow
cover. Here, the X-ray crystal structure of a hyperactive isoform, TisAFP8, at
1.0 A resolution is presented. TisAFP8 folds into a right-handed beta-helix
accompanied with a long alpha-helix insertion. TisAFP8 exhibited significantly
high antifreeze activity that is comparable with other hyperactive AFPs, despite
its close structural and sequence similarity with the moderately active isoform
TisAFP6. A series of mutations introduced into the putative ice-binding sites
(IBSs) in the beta-sheet and adjacent loop region reduced antifreeze activity. A
double-mutant A20T/A212S, which comprises a hydrophobic patch between the beta
sheet and loop region, caused the greatest depression of antifreeze activity of
75%, when compared with that of the wild-type protein. This shows that the loop
region is involved in ice binding and hydrophobic residues play crucial
functional roles. Additionally, bound waters around the beta-sheet and loop
region IBSs were organized into an ice-like network and can be divided into two
groups that appear to mediate separately TisAFP and ice. The docking model of
TisAFP8 with the basal plane via its loop region IBS reveals a better shape
complementarity than that of TisAFP6. In conclusion, we present new insights into
the ice-binding mechanism of TisAFP8 by showing that a higher hydrophobicity and
better shape complementarity of its IBSs, especially the loop region, may render
TisAFP8 hyperactive to ice binding.
PMID- 27613856
TI - Effects of dietary copper and amino acid density on growth performance, apparent
metabolizable energy, and nutrient digestibility in Eimeria acervulina-challenged
broilers.
AB - The objective of this experiment was to evaluate the influence of copper
supplementation in diets varying in amino acid (AA) density on growth
performance, apparent metabolizable energy (AMEn), apparent ileal nutrient
digestibility (AID), and plasma carotenoids in broilers infected with Eimeria
acervulina. Ross 308 male broilers (480 total) were housed in battery cages and
allotted to 8 experimental treatments in a factorial arrangement of 2 dietary AA
densities [1.00% (LAA) or 1.20% (HAA) digestible Lys], 2 supplemental copper
concentrations (zero or 116 mg/kg), and 2 E. acervulina infection states
(uninfected or infected). Essential AA ratios relative to digestible Lys were
similar in both the LAA and HAA diets, and copper was provided by 200 mg/kg of
tribasic copper chloride (58% copper). Chicks received experimental diets from 2
to 21 d post hatch and 6 replicate cages of 10 birds per cage were assigned to
each treatment. Broilers were inoculated with zero or 6.3 * 105 sporulated E.
acervulina oocysts at 15 d and blood and ileal digesta were collected at 21 days.
From 2 to 15 d, body weight gain and G:F of broilers were improved (P < 0.05)
with increasing AA density, and an AA density * copper interaction was observed
(P < 0.05) for feed intake. Eimeria infection reduced (P < 0.05) plasma
carotenoids, growth performance, dietary AMEn, and AID of organic matter,
nitrogen, and total AA. There were no interactive effects of dietary treatments
with E. acervulina infection on broiler growth performance or dietary AMEn. An AA
density * copper supplementation interaction was observed (P < 0.05) for AID of
total AA, whereby copper supplementation increased AID of total AA for birds fed
the LAA diet and decreased AID of total AA for birds fed the HAA diet. In
summary, E. acervulina-induced reductions in nutrient digestibility were
dependent on dietary copper and AA status, but changes in digestibility had
minimal impact on growth performance of broilers during the E. acervulina
infection period.
PMID- 27613858
TI - Crystal structure and enantioselectivity of terpene cyclization in SAM-dependent
methyltransferase TleD.
AB - TleD is a SAM (S-adenosyl-l-methionine)-dependent methyltransferase and acts as
one of the key enzymes in the teleocidin B biosynthesis pathway. Besides methyl
transferring, TleD also rearranges the geranyl and indole moieties of the
precursor to form a six-membered ring. Moreover, it does not show homologies with
any known terpenoid cyclases. In order to elucidate how such a remarkable
reaction could be achieved, we determined the complex crystal structures of TleD
and the cofactor analogue S-adenosyl-l-homocysteine with or without the substrate
teleocidin A1. A domain-swapped pattern via an additional N-terminal alpha-helix
is observed in TleD hexamers. Structural comparison and alignment shows that this
additional N-terminal alpha-helix is the common feature of SAM methyltransferase
like cyclases TleD and SpnF. The residue Tyr21 anchors the additional N-terminal
alpha-helix to a 'core SAM-MT fold' and is a key residue for catalytic activity.
Molecular dynamics simulation results suggest that the dihedral angle C23-C24-C25
C26 of teleocidin A1 is preferred to 60-90 degrees in the TleD and substrate
complex structure, which tend to adopt a Re-face stereocenter at C25 position
after reaction and is according to in vitro enzyme reaction experiments. Our
results also demonstrate that methyl transfer can be a new chemical strategy for
carbocation formation in the terpene cyclization, which is the key initial step.
PMID- 27613860
TI - Classic Spotlight: the Heat Shock Response and the Discovery of Alternative Sigma
Factors in Escherichia coli.
PMID- 27613859
TI - Classic Spotlight: Managing Stress.
PMID- 27613861
TI - Special Meeting Sections for the 7th ASM Conference on Biofilms.
PMID- 27613864
TI - Palmitoylation of Progressive Rod-Cone Degeneration (PRCD) Regulates Protein
Stability and Localization.
AB - Progressive rod-cone degeneration (PRCD) is a photoreceptor outer segment (OS)
disc-specific protein with unknown function that is associated with retinitis
pigmentosa (RP). The most common mutation in PRCD linked with severe RP phenotype
is substitution of the only cysteine to tyrosine (C2Y). In this study, we find
that PRCD is post-translationally modified by a palmitoyl lipid group at the
cysteine residue linked with RP. Disrupting PRCD palmitoylation either chemically
or by genetically eliminating the modified cysteine dramatically affects the
stability of PRCD. Furthermore, in vivo electroporation of PRCD C2Y mutant in the
mouse retina demonstrates that the palmitoylation of PRCD is important for its
proper localization in the photoreceptor OS. Mutant PRCD C2Y was found in the
inner segment in contrast to normal localization of WT PRCD in the OS. Our
results also suggest that zDHHC3, a palmitoyl acyltransferase (PAT), catalyzes
the palmitoylation of PRCD in the Golgi compartment. In conclusion, we find that
the palmitoylation of PRCD is crucial for its trafficking to the photoreceptor OS
and mislocalization of this protein likely leads to RP-related phenotypes.
PMID- 27613865
TI - Lipids Activate SecA for High Affinity Binding to the SecYEG Complex.
AB - Protein translocation across the bacterial cytoplasmic membrane is an essential
process catalyzed predominantly by the Sec translocase. This system consists of
the membrane-embedded protein-conducting channel SecYEG, the motor ATPase SecA,
and the heterotrimeric SecDFyajC membrane protein complex. Previous studies
suggest that anionic lipids are essential for SecA activity and that the N
terminus of SecA is capable of penetrating the lipid bilayer. The role of lipid
binding, however, has remained elusive. By employing differently sized nanodiscs
reconstituted with single SecYEG complexes and comprising varying amounts of
lipids, we establish that SecA gains access to the SecYEG complex via a lipid
bound intermediate state, whereas acidic phospholipids allosterically activate
SecA for ATP-dependent protein translocation.
PMID- 27613866
TI - Positive Allosteric Modulation of the Calcium-sensing Receptor by Physiological
Concentrations of Glucose.
AB - The calcium-sensing receptor (CaSR) is activated by various cations, cationic
compounds, and amino acids. In the present study we investigated the effect of
glucose on CaSR in HEK293 cells stably expressing human CaSR (HEK-CaSR cells).
When glucose concentration in the buffer was raised from 3 to 25 mm, a rapid
elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) was observed. This
elevation was immediate and transient and was followed by a sustained decrease in
[Ca2+]c The effect of glucose was detected at a concentration of 4 mm and reached
its maximum at 5 mm 3-O-Methylglucose, a non-metabolizable analogue of glucose,
reproduced the effect of glucose. Sucrose also induced an elevation of [Ca2+]c in
HEK-CaSR cells. Similarly, sucralose was nearly as effective as glucose in
inducing elevation of [Ca2+]c Glucose was not able to increase [Ca2+]c in the
absence of extracellular Ca2+ The effect of glucose on [Ca2+]c was inhibited by
NPS-2143, an allosteric inhibitor of CaSR. In addition, NPS-2143 also inhibited
the [Ca2+]c responses to sucralose and sucrose. Glucose as well as sucralose
decreased cytoplasmic cAMP concentration in HEK-CaSR cells. The reduction of cAMP
induced by glucose was blocked by pertussis toxin. Likewise, sucralose reduced
[cAMP]c Finally, glucose increased [Ca2+]c in PT-r parathyroid cells and in Madin
Darby canine kidney cells, both of which express endogenous CaSR. These results
indicate that glucose acts as a positive allosteric modulator of CaSR.
PMID- 27613867
TI - Peroxisome Proliferator-activated Receptor-gamma Activation Augments the beta
Cell Unfolded Protein Response and Rescues Early Glycemic Deterioration and beta
Cell Death in Non-obese Diabetic Mice.
AB - Type 1 diabetes is an autoimmune disorder that is characterized by a failure of
the unfolded protein response in islet beta cells with subsequent endoplasmic
reticulum stress and cellular death. Thiazolidinediones are insulin sensitizers
that activate the nuclear receptor PPAR-gamma and have been shown to partially
ameliorate autoimmune type 1 diabetes in humans and non-obese diabetic (NOD)
mice. We hypothesized that thiazolidinediones reduce beta cell stress and death
independently of insulin sensitivity. To test this hypothesis, female NOD mice
were administered pioglitazone during the pre-diabetic phase and assessed for
insulin sensitivity and beta cell function relative to controls. Pioglitazone
treated mice showed identical weight gain, body fat distribution, and insulin
sensitivity compared with controls. However, treated mice showed significantly
improved glucose tolerance with enhanced serum insulin levels, reduced beta cell
death, and increased beta cell mass. The effect of pioglitazone was independent
of actions on T cells, as pancreatic lymph node T cell populations were unaltered
and T cell proliferation was unaffected by pioglitazone. Isolated islets of
treated mice showed a more robust unfolded protein response, with increases in
Bip and ATF4 and reductions in spliced Xbp1 mRNA. The effect of pioglitazone
appears to be a direct action on beta cells, as islets from mice treated with
pioglitazone showed reductions in PPAR-gamma (Ser-273) phosphorylation. Our
results demonstrate that PPAR-gamma activation directly improves beta cell
function and survival in NOD mice by enhancing the unfolded protein response and
suggest that blockade of PPAR-gamma (Ser-273) phosphorylation may prevent type 1
diabetes.
PMID- 27613868
TI - The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form
Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA
Export.
AB - Genetic rearrangements are a hallmark of several forms of leukemia and can lead
to oncogenic fusion proteins. One example of an affected chromosomal region is
the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side
of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET
Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of
Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1
were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET
Nup214 in HeLa cells leads to the formation of similar nuclear bodies that
recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly
affect nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214, although mostly
cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not
poly(A)+ RNA export. The interaction of the fusion proteins with CRM1 is RanGTP
dependent, as shown in co-immunoprecipitation experiments and binding assays.
Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear
export, whereas the SET or SQSTM1 part determines the localization of the fusion
protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are
highly mobile structures, which are in equilibrium with the nucleoplasm in
interphase and disassemble during mitosis or upon treatment of cells with the
CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be
released from nuclear bodies and reintegrated into existing NPC. Our results
point to nuclear bodies as a means of preventing the formation of potentially
insoluble and harmful protein aggregates that also may serve as storage
compartments for nuclear transport factors.
PMID- 27613870
TI - Phosphorylation Controls Endothelial Nitric-oxide Synthase by Regulating Its
Conformational Dynamics.
AB - The activity of endothelial NO synthase (eNOS) is triggered by calmodulin (CaM)
binding and is often further regulated by phosphorylation at several positions in
the enzyme. Phosphorylation at Ser1179 occurs in response to diverse physiologic
stimuli and increases the NO synthesis and cytochrome c reductase activities of
eNOS, thereby enhancing its participation in biological signal cascades. Despite
its importance, the mechanism by which Ser1179 phosphorylation increases eNOS
activity is not understood. To address this, we used stopped-flow spectroscopy
and computer modeling approaches to determine how the phosphomimetic mutation
(S1179D) may impact electron flux through eNOS and the conformational behaviors
of its reductase domain, both in the absence and presence of bound CaM. We found
that S1179D substitution in CaM-free eNOS had multiple effects; it increased the
rate of flavin reduction, altered the conformational equilibrium of the reductase
domain, and increased the rate of its conformational transitions. We found these
changes were equivalent in degree to those caused by CaM binding to wild-type
eNOS, and the S1179D substitution together with CaM binding caused even greater
changes in these parameters. The modeling indicated that the changes caused by
the S1179D substitution, despite being restricted to the reductase domain, are
sufficient to explain the stimulation of both the cytochrome c reductase and NO
synthase activities of eNOS. This helps clarify how Ser1179 phosphorylation
regulates eNOS and provides a foundation to compare its regulation by other
phosphorylation events.
PMID- 27613871
TI - Substrate and Cofactor Dynamics on Guanosine Monophosphate Reductase Probed by
High Resolution Field Cycling 31P NMR Relaxometry.
AB - Guanosine-5'-monophosphate reductase (GMPR) catalyzes the reduction of GMP to IMP
and ammonia with concomitant oxidation of NADPH. Here we investigated the
structure and dynamics of enzyme-bound substrates and cofactors by measuring 31P
relaxation rates over a large magnetic field range using high resolution field
cycling NMR relaxometry. Surprisingly, these experiments reveal differences in
the low field relaxation profiles for the monophosphate of GMP compared with IMP
in their respective NADP+ complexes. These complexes undergo partial reactions
that mimic different steps in the overall catalytic cycle. The relaxation
profiles indicate that the substrate monophosphates have distinct interactions in
E.IMP.NADP+ and E.GMP.NADP+ complexes. These findings were not anticipated by x
ray crystal structures, which show identical interactions for the monophosphates
of GMP and IMP in several inert complexes. In addition, the motion of the
cofactor is enhanced in the E.GMP.NADP+ complex. Last, the motions of the
substrate and cofactor are coordinately regulated; the cofactor has faster local
motions than GMP in the deamination complex but is more constrained than IMP in
that complex, leading to hydride transfer. These results show that field cycling
can be used to investigate the dynamics of protein-bound ligands and provide new
insights into how portions of the substrate remote from the site of chemical
transformation promote catalysis.
PMID- 27613869
TI - The Rab3A-22A Chimera Prevents Sperm Exocytosis by Stabilizing Open Fusion Pores.
AB - At the final stage of exocytotis, a fusion pore opens between the plasma and a
secretory vesicle membranes; typically, when the pore dilates the vesicle
releases its cargo. Sperm contain a large dense-core secretory granule (the
acrosome) whose contents are secreted by regulated exocytosis at fertilization.
Minutes after the arrival of the triggering signal, the acrosomal and plasma
membranes dock at multiple sites and fusion pores open at the contact points. It
is believed that immediately afterward, fusion pores dilate spontaneously. Rab3A
is an essential component of human sperm exocytotic machinery. Yet, recombinant,
persistently active Rab3A halts calcium-triggered secretion when introduced after
docking into streptolysin O-permeabilized cells; so does a Rab3A-22A chimera.
Here, we applied functional assays, electron and confocal microscopy to show that
the secretion blockage is due to the stabilization of open fusion pores. Other
novel findings are that sperm SNAREs engage in alpha-SNAP/NSF-sensitive complexes
at a post-fusion stage. Complexes are disentangled by these chaperons to achieve
vesiculation and acrosomal contents release. Thus, post-fusion regulation of the
pores determines their expansion and the success of the acrosome reaction.
PMID- 27613872
TI - Targeting Liver Fibrosis with a Cell-penetrating Protease-activated Receptor-2
(PAR2) Pepducin.
AB - Chronic liver inflammation and fibrosis in nonalcoholic steatohepatitis can lead
to cirrhosis and liver failure for which there are currently no approved
treatments. Protease-activated receptor-2 (PAR2) is an emerging new target
expressed on liver stellate cells and hepatocytes that regulates the response to
liver injury and inflammation. Here, we identified a pepducin to block the
deleterious actions of PAR2 in promoting liver fibrosis. Non-alcoholic fatty
liver disease and early fibrosis were induced by the methionine-choline-deficient
diet in mice. Fibrotic liver disease was induced by administering carbon
tetrachloride for 8 weeks. Mice were treated with the pepducin PZ-235 either from
onset of the experiment or after fibrosis was established. Hepatic fibrosis,
collagen content, inflammatory cytokines, steatosis, triglycerides, and NAFLD
activity score were assessed as primary outcome parameters depending on the
model. The activity of the PAR2 pepducin on cultured stellate cell activation and
hepatocyte reactive oxygen species production was evaluated. PZ-235 significantly
suppressed liver fibrosis, collagen deposition, inflammatory cytokines, NAFLD
activity score, steatosis, triglycerides, aspartate transaminase, alanine
transaminase, and stellate cell proliferation by up to 50-100%. The PAR2
inhibitor afforded significant protective effects against hepatocellular necrosis
and attenuated PAR2-mediated reactive oxygen species production in hepatocytes.
PZ-235 was distributed to liver and other mouse tissues and was found to form a
well structured alpha-helix that closely resembles the juxtamembrane helical
region of the analogous TM6 and third intracellular region of the intact receptor
that is critical for coupling to internal G proteins. The ability of PZ-235 to
effectively suppress fibrosis, hepatocellular necrosis, reactive oxygen species
production, steatosis, and inflammation indicates the potential for PAR2 pepducin
inhibitors to be broadly efficacious in the treatment of liver fibrosis.
PMID- 27613854
TI - Morphometricity as a measure of the neuroanatomical signature of a trait.
AB - Complex physiological and behavioral traits, including neurological and
psychiatric disorders, often associate with distributed anatomical variation.
This paper introduces a global metric, called morphometricity, as a measure of
the anatomical signature of different traits. Morphometricity is defined as the
proportion of phenotypic variation that can be explained by macroscopic brain
morphology. We estimate morphometricity via a linear mixed-effects model that
uses an anatomical similarity matrix computed based on measurements derived from
structural brain MRI scans. We examined over 3,800 unique MRI scans from nine
large-scale studies to estimate the morphometricity of a range of phenotypes,
including clinical diagnoses such as Alzheimer's disease, and nonclinical traits
such as measures of cognition. Our results demonstrate that morphometricity can
provide novel insights about the neuroanatomical correlates of a diverse set of
traits, revealing associations that might not be detectable through traditional
statistical techniques.
PMID- 27613873
TI - N6-Methyladenosine Sequencing Highlights the Involvement of mRNA Methylation in
Oocyte Meiotic Maturation and Embryo Development by Regulating Translation in
Xenopus laevis.
AB - During the oogenesis of Xenopus laevis, oocytes accumulate maternal materials for
early embryo development. As the transcription activity of the oocyte is silenced
at the fully grown stage and the global genome is reactivated only by the mid
blastula embryo stage, the translation of maternal mRNAs accumulated during
oocyte growth should be accurately regulated. Previous evidence has illustrated
that the poly(A) tail length and RNA binding elements mediate RNA translation
regulation in the oocyte. Recently, RNA methylation has been found to exist in
various systems. In this study, we sequenced the N6-methyladenosine (m6A)
modified mRNAs in fully grown germinal vesicle-stage and metaphase II-stage
oocytes. As a result, we identified 4207 mRNAs with m6A peaks in germinal vesicle
stage or metaphase II-stage oocytes. When we integrated the mRNA methylation data
with transcriptome and proteome data, we found that the highly methylated mRNAs
showed significantly lower protein levels than those of the hypomethylated mRNAs,
although the RNA levels showed no significant difference. We also found that the
hypomethylated mRNAs were mainly enriched in the cell cycle and translation
pathways, whereas the highly methylated mRNAs were mainly associated with protein
phosphorylation. Our results suggest that oocyte mRNA methylation can regulate
cellular translation and cell division during oocyte meiotic maturation and early
embryo development.
PMID- 27613875
TI - Root-endophytes improve the ecophysiological performance and production of an
agricultural species under drought condition.
AB - Throughout many regions of the world, climate change has limited the availability
of water for irrigating crops. Indeed, current models of climate change predict
that arid and semi-arid zones will be places where precipitation will drastically
decrease. In this context, plant root-associated fungi appear as a new strategy
to improve ecophysiological performance and yield of crops under abiotic stress.
Thus, use of fungal endophytes from ecosystems currently subjected to severe
drought conditions could improve the ecophysiological performance and quantum
yield of crops exposed to drought. In this study, we evaluated how the
inoculation of fungal endophytes isolated from Antarctic plants can improve the
net photosynthesis, water use efficiency and production of fresh biomass in a
lettuce cultivar, grown under different water availability regimes. In addition,
we assessed if the presence of biochemical mechanisms and gene expression related
with environmental tolerance are improved in presence of fungal endophytes.
Overall, those individuals with presence of endophytes showed higher net
photosynthesis and maintained higher water use efficiency in drought conditions,
which was correlated with greater fresh and dry biomass production as well as
greater root system development. In addition, presence of fungal endophytes was
correlated with a higher proline concentration, lower peroxidation of lipids and
up-/down-regulation of ion homeostasis. Our results suggest that presence of
fungal endophytes could minimize the negative effect of drought by improving
drought tolerance through biochemical mechanisms and improving nutritional
status. Thus, root-endophytes might be a successful biotechnological tool to
maintain high levels of ecophysiological performance and productivity in zones
under drought.
PMID- 27613874
TI - T cell subsets: an immunological biomarker to predict progression to clinical
arthritis in ACPA-positive individuals.
AB - OBJECTIVES: Anticitrullinated protein antibody (ACPA)+ individuals with non
specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA).
This study aims to demonstrate the predictive value of T cell subset
quantification for progression towards IA and compare it with previously
identified clinical predictors of progression. METHODS: 103 ACPA+ individuals
without clinical synovitis were observed 3-monthly for 12 months and then as
clinically indicated. The end point was the development of IA. Naive, regulatory
T cells (Treg) and inflammation related cells (IRCs) were quantified by flow
cytometry. Areas under the ROC curve (AUC) were calculated. Adjusted logistic
regressions and Cox proportional hazards models for time to progression to IA
were constructed. RESULTS: Compared with healthy controls (age adjusted where
appropriate), ACPA+ individuals demonstrated reduced naive (22.1% of subjects)
and Treg (35.8%) frequencies and elevated IRC (29.5%). Of the 103 subjects,
48(46.6%) progressed. Individually, T cell subsets were weakly predictive (AUC
between 0.63 and 0.66), although the presence of 2 T cell abnormalities had high
specificity. Three models were compared: model-1 used T cell subsets only, model
2 used previously published clinical parameters, model-3 combined clinical data
and T cell data. Model-3 performed the best (AUC 0.79 (95% CI 0.70 to 0.89))
compared with model-1 (0.75 (0.65 to 0.86)) and particularly with model-2 (0.62
(0.54 to 0.76)) demonstrating the added value of T cell subsets. Time to
progression differed significantly between high-risk, moderate-risk and low-risk
groups from model-3 (p=0.001, median 15.4 months, 25.8 months and 63.4 months,
respectively). CONCLUSIONS: T cell subset dysregulation in ACPA+ individuals
predates the onset of IA, predicts the risk and faster progression to IA, with
added value over previously published clinical predictors of progression.
PMID- 27613878
TI - Celebrating 35 Years of the AJNR: September 1981 edition.
PMID- 27613879
TI - Beliefs, Practices, and Self-efficacy of US Physicians Regarding Smoking
Cessation and Electronic Cigarettes: A National Survey.
AB - INTRODUCTION: We sought to assess physician knowledge/beliefs, self-efficacy, and
experience/practice patterns surrounding smoking cessation and electronic
cigarettes. METHODS: An eight-page survey sent via US Postal service. The initial
invitation included a $10 cash incentive and up to three invitations were sent.
Fifteen hundred US physicians were identified with equal representation from
primary care physicians (internal medicine and family practice), surgical care
physicians (general surgeons and anesthesiologists), and pulmonologists. RESULTS:
Two hundred fourteen were not included in the analysis (183 non-deliverable, one
deceased, 30 not practicing). 561/1286 (44%) remaining surveys were returned for
analysis. Greater than 90% agreed that advising and assisting with smoking
cessation is their responsibility; 86% advise and 65% assist their patients with
smoking cessation more than 75% of the time. Approximately two-thirds of
respondents report that their patients ask them about electronic cigarettes at
least some of the time (>=25%); 58.4% report that they ask their patients about
electronic cigarette use at least some of the time. Overall, 37.9% have at some
point recommended electronic cigarettes to their patients that smoke, with 11.5%
reporting recommending them at least 25% of the time. Surgical care providers
appear less confident and less self-efficacious with smoking cessation, as well
as with electronic cigarettes and appear less likely to endorse use of electronic
cigarettes. DISCUSSION: US physicians are frequently discussing electronic
cigarettes in a clinical context and a substantial proportion of US physicians
have recommended electronic cigarettes to their patients. IMPLICATIONS: This
study documents several important previously poorly characterized aspects of the
role of electronic cigarettes in clinical care. The majority of US physicians are
discussing electronic cigarettes in clinical contexts and a substantial
proportion of US physicians have recommended electronic cigarettes to their
patients. The extent of physician engagement on the topic of electronic
cigarettes should be met with increased efforts to better characterize electronic
cigarettes' appropriate role in smoking cessation and reduction.
PMID- 27613876
TI - The effects of aluminium on plant growth in a temperate and deciduous aluminium
accumulating species.
AB - Aluminium (Al) is a phytotoxic element affecting the growth and yield of many
crop plants, especially in the tropics. Yet, some plants are able to accumulate
high levels of Al. The monogeneric family Symplocaceae represents an Al
accumulating family including many tropical and evergreen species with high Al
levels in their above ground plant tissues. It is unclear, however, whether Al
accumulation also characterises temperate species of Symplocos, and whether or
not the uptake has a beneficial growth effect. Here, we investigate if the
temperate, deciduous species Symplocos paniculata is able to accumulate Al by
growing seedlings and saplings in a hydroponic setup at pH 4 with and without Al.
Pyrocatechol-violet (PCV) and aluminon staining was performed to visualize Al
accumulation in various plant tissues. Both seedlings and saplings accumulate Al
in their tissues if available. Mean Al levels in leaves were 4107 (+/-1474 mg kg
1) and 4290 (+/-4025 mg kg-1) for the seedlings and saplings, respectively. The
saplings treated without Al showed a high mortality rate unlike the Al
accumulating ones. The seedlings, however, showed no difference in growth and
vitality between the two treatments. The saplings treated with Al showed new
twig, leaf and root development, resulting in a considerable biomass increase.
PCV and aluminon staining indicated the presence of Al in leaf, wood and bark
tissue of the plants. S. paniculata shares the capacity to accumulate Al with its
tropical sister species and is suggested to be a facultative accumulator. Whether
or not Al has a beneficial effect remains unclear, due to developmental
differences between seedlings and saplings. Al is suggested to be transported via
the xylem transport system into the leaves, which show the highest Al levels.
Radial transport via ray parenchyma to bark tissue is also likely given the high
Al concentrations in the bark tissue.
PMID- 27613880
TI - A Pilot Randomized Crossover Trial of Electronic Cigarette Sampling Among
Smokers.
AB - INTRODUCTION: Electronic cigarette (EC) use is proliferating, but initial uptake
patterns and their influence on smoking remains unclear. This study of EC
sampling examines naturalistic uptake of ECs, as well as effects on smoking and
perceived reward from smoking and vaping. METHODS: Within a double-blind
randomized crossover design, smokers (n = 24; 75% male; M age = 48.5 years)
smoked as usual for 1 week, followed by two counterbalanced naturalistic (ie, ad
libitum use) weeks of either placebo or active first generation ECs. Vaping and
regular smoking was measured daily using diaries and at weekly clinic visits.
Perceived reward from ECs and intentions/confidence to quit were also assessed.
Analyses compared variables during the naturalistic smoking week and each EC week
while controlling for sequence and baseline measurements of respective variables.
RESULTS: No significant differences emerged between active and placebo EC weeks
in vaping or regular smoking, EC reinforcement, and intention/confidence to quit
smoking. Satisfaction from smoking (p = .04) and smoking's ability to reduce
cravings (p = .003) decreased from the naturalistic to active EC week. Behavioral
dependence to cigarettes decreased from the naturalistic (M = 16.5, p = .02) to
active (M = 14.7) and placebo (M = 14.2) EC weeks. CONCLUSIONS: Few differences
emerged in vaping, regular cigarette use, and overall reactions to ECs between
active and placebo ECs. Active ECs appeared to decrease reinforcement from
smoking, and both active and placebo ECs reduced behavioral dependence to
cigarettes. Nicotine (per labeling) may have minimal influence on the uptake of
first generation ECs among smokers. IMPLICATIONS: First generation ECs provide an
important behavioral/sensorimotor replacement for cigarettes, regardless of
nicotine delivery, but substantial substitution may be minimal when smokers are
only asked to use ad libitum. However, newer models of EC devices that provide
better nicotine delivery should be examined for potential differential patterns
of smoking and vaping (eg, decreased smoking and increased vaping) given their
suggested greater ability to provide nicotine and behavior/sensorimotor
replacement.
PMID- 27613881
TI - Smokers' Perceptions of the Relative Effectiveness of Five Tobacco Retail
Reduction Policies.
AB - INTRODUCTION: Reducing the widespread retail availability of tobacco could help
realize tobacco endgame strategies. We assessed New Zealand smokers' perceptions
of five potential policies designed to reduce the retail supply of tobacco,
relative to a "benchmark" policy of annual tobacco tax increases. METHODS: A
sample of 623 smokers was recruited from an internet panel. Participants
evaluated one of six randomly assigned policy scenarios that would reduce tobacco
outlet density: (1) no tobacco sold at alcohol on-licensed premises, (2) no
tobacco sold within 500 m of a high school, (3) no tobacco sold within 1 km of
any school, (4) tobacco sold only at pharmacies, and (5) tobacco sold only at
half the existing liquor stores. Continued 10% annual tobacco tax increases
served as a benchmark condition. Participants rated the likely effectiveness of
one policy on preventing uptake by a 15-year-old susceptible never-smoker and
supporting quitting by an adult smoker. Analyses involved pooled t tests and
logistic regression. RESULTS: The policy scenarios in which tobacco was only sold
at half the existing liquor stores or only at pharmacies were rated more likely
to prevent youth smoking initiation, and at least as likely to help smokers to
quit, relative to the benchmark policy. CONCLUSIONS: This is the first study to
compare potential retail interventions against a measure known to reduce smoking
prevalence. Policies that substantially reduce tobacco availability and remove it
from smokers' usual places of purchase are perceived as being at least as
effective in reducing smoking initiation and supporting cessation, as tax
increases. IMPLICATIONS: Tobacco control advocates have proposed a range of
policies to reduce tobacco retail outlet density, as part of endgame strategies.
There are no published data on the relative effectiveness of different
approaches, therefore it is unclear which would be most likely to reduce smoking
prevalence. This study provides an insight into smokers' perspectives on the
effectiveness of retail reduction strategies and indicates that some of these
could be at least as effective in reducing initiation and promoting quitting as
tax increases. Smokers' perceptions of the relative effectiveness of these policy
options may help inform the advocacy efforts of the sector.
PMID- 27613883
TI - Does High Tobacco Consumption Cause Psychological Distress? A Mendelian
Randomization Study.
AB - BACKGROUND: Increasing evidence suggests that smoking influences mental health
negatively. This study investigated whether high tobacco consumption is causally
related to psychological distress in a Mendelian randomization design, using a
variant in the nicotine acetylcholine receptor gene CHRNA3-known to influence
individual tobacco consumption-as instrumental variable for tobacco consumption.
METHODS: Data from 90 108 participants in the Copenhagen General Population Study
was used. Exposures included self-reported cigarettes/day and pack years and the
CHRNA3 rs1051730 genotype as instrumental variable for tobacco consumption. Three
dimensions of psychological distress were studied: Stress, fatigue, and
hopelessness. Analyses with the CHRNA3 genotype were stratified by smoking
status. RESULTS: Self-reported amount of smoking was associated with all three
dimensions of psychological distress. For instance among participants smoking 30
cigarettes/day or more, the odds ratio (OR) for stress was 1.67 (95% confidence
interval [CI] 1.47-1.89) compared to never-smokers. Corresponding ORs for fatigue
and hopelessness were 2.18 (95% CI 1.92-2.47) and 3.08 (95% CI 2.62-3.62). Among
current smokers, homozygotes and heterozygotes for the CHRNA3 genotype had higher
tobacco consumption than noncarriers. Nevertheless, the CHRNA3 genotype was not
associated with psychological distress neither in current nor in former or never
smokers. For instance among current smokers, the OR for stress was 1.02 (95% CI
0.91-1.15) among homozygotes compared to noncarriers of the CHRNA3 genotype.
CONCLUSIONS: Though a strong association between tobacco consumption and
psychological distress was found, there was no clear evidence that high tobacco
consumption was causally related to psychological distress. IMPLICATIONS: Smoking
is associated with several mental health outcomes and smoking cessation is
associated with improved mental health. Causality in the association between
smoking and mental health is difficult to establish using observational data.
Using a genotype known to influence tobacco consumption as instrumental variable
for amount of smoking, we found no clear evidence of a direct causal path between
high tobacco consumption and psychological distress. Whatever causes the strong
association between tobacco consumption and psychological distress, the co
occurrence is important to consider both in interventions for smoking prevention
and cessation.
PMID- 27613882
TI - Classification Tree Analysis as a Method for Uncovering Relations Between
CHRNA5A3B4 and CHRNB3A6 in Predicting Smoking Progression in Adolescent Smokers.
AB - Introduction: Prior research suggests the CHRNA5A3B4 and CHRNB3A6 gene clusters
have independent effects on smoking progression in young smokers. Here
classification tree analysis uncovers conditional relations between these genes.
Methods: Conditional classification tree and random forest analyses were employed
to predict daily smoking at 6-year follow-up in a longitudinal sample of young
smokers (N = 480) who had smoked at least one puff at baseline and were of
European ancestry. Potential predictors included gender, lifetime smoking,
Nicotine Dependence Syndrome Scale (NDSS), and five single nucleotide
polymorphisms (SNPs) tagging CHRNB3A6 and CHRNA5A3B4 Haplotypes A, B, and C.
Conditional random forest analysis was used to calculate variable importance.
Results: The classification tree identified NDSS, the CHRNB3A6 SNP rs2304297, and
the CHRNA5A3B4 Haplotype C SNP rs6495308 as predictive of year 6 daily smoking
with the baseline NDSS identified as the strongest predictor. The CHRNB3A6
protective effect was contingent on a lower level of baseline NDSS, whereas the
CHRNA5A3B4 Haplotype C protective effect was seen at a higher level of baseline
NDSS. A CHRNA5A3B4 Haplotype C protective effect also was observed in
participants with low baseline NDSS who had no CHRNB3A6 rs2304297 minor allele.
Conclusions: The protective effects of CHRNA5A3B4 Haplotype C and CHRNB3A6 on
smoking progression are conditional on different levels of baseline cigarette
use. Also, duplicate dominant epistasis between SNPs indicated the minor allele
of either SNP afforded comparable protective effects in the absence of a minor
allele at the other locus. Possible mechanisms underlying these conditional
relations are discussed. Implications: The substantive contributions of this
paper are the demonstration of a difference in the protective effects of CHRNB3A6
and CHRNA5A3B4 Haplotype C in young smokers attributable to level of cigarette
use, as well as observation of duplicate dominant epistasis between the two
markers. The methodological contribution is demonstrating that classification
tree and random forest statistical methods can uncover conditional relations
among genetic effects not detected with more common regression methods.
PMID- 27613884
TI - Changes in Smoking Rates Among Pregnant Women and the General Female Population
in Australia, Finland, Norway, and Sweden.
AB - Introduction: Smoking rates have dropped substantially in most developed
countries in recent decades. This general trend has, however, not always been
evident among women-particularly younger women. Smoking habits do, however, often
change in connection with pregnancy and the aim of this study is to determine
whether smoking during pregnancy follows general trends in smoking rates in the
general female population in four countries with active anti-tobacco policies and
decreasing population smoking rates. Methods: Changes in rates of persistent
smoking, that is, smoking in late pregnancy or daily smoking among all women of
childbearing age were described according to age groups. Data were retrieved from
the Australian Household Drug Surveys during 2000-2013 and from registries and
surveys in Finland, Norway, and Sweden between 1995 and 2014. Results: In
general, persistent smoking has decreased and late-pregnancy smoking rates are
lower than daily smoking rates among all women. However, younger women are more
likely to be persistent smokers regardless of pregnancy status. In Norway and
Finland, persistent smoking was most common among young pregnant women and in
Sweden there was an increased polarization between age groups. In Australia, a
steady decrease in smoking rates appears to have stalled in younger pregnant
women. Conclusion: Although smoking has declined substantially in recent decades,
there are groups lagging behind this general trend. Young pregnant women are of
particular concern in this respect. The possibility that these findings reflect
the changing characteristics of younger pregnant women is discussed.
Implications: This study puts recent trends in maternal smoking into a broader
context by relating developments to changes in smoking rates among women in
general. By using similar data from four countries we were able to follow changes
in smoking rates "within" groups of women within the four countries without being
limited by methodological problems related to cross-country or inter-group
comparisons. We were above all able to show that aggregate data disclose the
strong age gradient in maternal smoking habits.
PMID- 27613887
TI - How Valid and Reliable are Cigarette Retail Sales Data for Estimating Population
Cigarette Consumption? A Case Study in Scotland.
PMID- 27613886
TI - Severity of Nicotine Addiction and Disruptions in Sleep Mediated by Early
Awakenings.
AB - INTRODUCTION: Sleep disruption is common among smokers, however, extant studies
primarily explore differences between smokers and nonsmokers. The time to
smokers' first cigarette of the day (TTFC) after waking, a strong indicator of
addiction severity, is inversely associated with numerous health outcomes. The
present study tests the hypotheses that, in a representative sample of daily
smokers, the severity of nicotine addiction is associated with shorter habitual
sleep duration and excessive daytime sleepiness. METHODS: We examined the
associations between TTFC and sleep outcomes (sleep duration and daytime
excessive sleepiness) and the mediating effects of specific sleep disruption
pathways (delayed sleep onset, awakenings at night, and early awakening) using
structural equation modeling. Analyses included cross-sectional data from 2015
current daily smokers aged 16-85 years who participated in the 2005-2006 and 2007
2008 National Health and Nutrition Examination Survey. RESULTS: Among daily
smokers, earlier TTFC was associated with both shorter sleep duration and
excessive daytime sleepiness (p values < .001, R 2 values = .15 and .29,
respectively). Of sleep disruption pathways, only early awakening mediated the
associations of TTFC with both outcomes (sleep duration: b = .02, 95% confidence
interval [CI]: 0.006 to 0.042; daytime sleepiness: b = -.01, 95% CI: -0.03 to
0.004), even after controlling for variables confounded with smoking status and
sleep outcomes. CONCLUSIONS: Findings suggest that early awakening may be the
mechanism responsible for the association between nicotine addiction severity and
poor sleep outcomes of shorter sleep duration and excessive daytime sleepiness.
These data may inform cessation strategies, risk assessment, and future
longitudinal studies on the relations between sleep and nicotine addiction.
IMPLICATIONS: Smokers have impaired sleep quality and quantity as compared to
nonsmokers; however, that severity of nicotine addiction is an important factor
in sleep quality, not just smoking status. Higher levels of addiction lead to
less sleep and more daytime sleepiness. The relation between addiction severity
and sleep is mediated by waking too early in the morning, and not by difficulty
falling asleep or waking during the night. These findings could play an important
role in supplementing cessation efforts; sleep disruption may interact with other
negative physiological and emotional symptoms related to nicotine withdrawal and
could result in more cessation failure.
PMID- 27613885
TI - Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and
Without Elevated Depressive Symptoms.
AB - BACKGROUND: The FDA recently acquired regulatory authority over tobacco products,
leading to renewed interest in whether reducing the nicotine content of
cigarettes would reduce tobacco dependence in the United States. Given the
association between depressive symptoms and cigarette smoking, it is important to
consider whether smokers with elevated depressive symptoms experience unique
benefits or negative consequences of nicotine reduction. METHODS: In this
secondary analysis of a randomized clinical trial that examined the effects of
cigarettes varying in nicotine content over a 6-week period in non-treatment
seeking smokers, we used linear regression to examine whether baseline depressive
symptom severity (scores on the Center for Epidemiologic Studies Depression Scale
[CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes,
relative to normal-nicotine content (NNC) cigarettes, on smoking rates,
depressive symptom severity, and related subjective and physiological measures.
RESULTS: Of the 717 participants included in this analysis, 109 (15.2%) had CES-D
scores >= 16, indicative of possible clinical depression. Relative to NNC
cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and
cigarette craving, and these effects were not significantly moderated by baseline
CES-D score. A significant interaction between baseline CES-D score and cigarette
condition on week 6 CES-D score was observed (p < .05); among those with CES-D
scores >= 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D
scores than those assigned to NNC cigarettes. Among those in the lowest nicotine
content conditions, biochemically confirmed compliance with the RNC cigarettes
was associated with an increase in CES-D score for those with baseline CES-D
scores < 16 and no change in CES-D score for those with baseline CES-D scores >=
16. CONCLUSIONS: These findings provide initial evidence that a reduced-nicotine
standard for cigarettes may reduce smoking, without worsening depressive
symptoms, among smokers with elevated depressive symptoms. IMPLICATIONS: This
secondary analysis of a recent clinical trial examined whether depressive symptom
severity moderated the effects of reduced-nicotine cigarettes on smoking and
depressive symptoms. Results indicate that, regardless of baseline depressive
symptoms, participants randomized to reduced-nicotine cigarettes had lower
smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post
randomization than those assigned to normal-nicotine cigarettes. In participants
with higher baseline depressive symptoms, those assigned to reduced-nicotine
cigarettes had lower week 6 depressive symptoms than those assigned to normal
nicotine cigarettes. These results suggest that a nicotine reduction policy could
have beneficial effects for smokers, regardless of depressive symptom severity.
PMID- 27613889
TI - Little Cigars and Cigarillos Use Among Young Adult Cigarette Smokers in the
United States: Understanding Risk of Concomitant Use Subtypes.
AB - INTRODUCTION: In 2016, the Food and Drug Administration announced that it would
regulate little cigars and cigarillos (LCCs) and expressed concern about the
concomitant use of combustible tobacco products. To understand LCC use among
socially-disadvantaged cigarette smokers, we assessed (1) the prevalence of
concomitant use of subtypes of LCCs: LCC-tobacco, LCC-blunt, and LCC- poly use,
which includes use of both LCC-tobacco and LCC-blunt and (2) and its association
with sociodemographic factors and substance use behaviors using race/ethnicity
and gender stratified models. METHODS: In 2015, a web-based survey was
administered to a national probability sample of black/African American,
Hispanic/Latino, and white cigarette smokers aged 18-44 (n = 1018). Weighted
estimates were used to assess current LCC-tobacco, LCC-blunt, and LCC-poly use.
Multinomial regression models assessed sociodemographic, other tobacco and
substance use correlates associated with LCC user subtypes. RESULTS: Of cigarette
smokers, 63% did not smoke LCCs; 15.1% were LCC-tobacco users; 11.1% were LCC
blunt users; and 10.5% were LCC-poly users. Black/African American and
Hispanic/Latino cigarette smokers had higher odds of LCC-tobacco, LCC-blunt, and
LCC-poly use compared to white cigarette smokers. Blacks/African Americans who
initiated cigarette smoking before age 18 and smoked other tobacco products had
greater odds of LCC-tobacco use than whites. Male cigarette smokers who smoked
other tobacco products and females who had early onset of cigarette use also had
greater odds of LCC-tobacco use. CONCLUSIONS: Over 30% of cigarette smokers
concomitantly used LCCs, which may prolong smoking. Accurate estimates of diverse
LCC use behaviors may increase our understanding of the potential harms of
concomitant use. IMPLICATIONS: Aggregate measures of LCC smoking do not
distinguish subtypes of use among socially-disadvantaged cigarette smokers (ie,
young adults, blacks/African Americans, Hispanics/Latinos), who may engage in
these unique smoking behaviors. We document the prevalence of young adult
cigarette smokers who dual use LCC-tobacco and LCC-blunts and are poly users of
LCC-tobacco + LCC-blunts, and identify sociodemographic groups at risk for use.
The Food and Drug Administration is concerned about concomitant behavior, which
may increase chronic disease risk and addiction. Accurate estimates of LCC
smoking behaviors may increase our understanding of the harms of concomitant use;
which can inform prevention programs that specifically target LCC subtypes.
PMID- 27613888
TI - Combination Extended Smoking Cessation Treatment Plus Home Visits for Smokers
With Schizophrenia: A Randomized Controlled Trial.
AB - INTRODUCTION: The majority of people with schizophrenia have a diagnosis of
tobacco dependence during their lifetime. A major obstacle to reducing the burden
of cigarette smoking in this population is that these smokers have lower quit
rates when undergoing standard treatment compared to smokers with no mental
illness. We sought to determine if combination extended treatment (COMB-EXT) and
home visits (HV) would lead to improved outcomes in smokers with schizophrenia.
METHODS: Thirty-four cigarette smokers with schizophrenia completed either COMB
EXT with HV, COMB-EXT without HV, or treatment as usual (TAU) (random
assignment). COMB-EXT consisted of group cognitive-behavioral therapy (CBT),
bupropion, nicotine patch, and nicotine lozenge, which were initiated within 2
weeks and continued for 26 weekly visits. HV consisted of biweekly visits to the
home with assessment of secondhand smoke (SHS) exposure and brief behavioral
therapy with participants and others in the home environment. TAU consisted of
group CBT plus serial single or combination medication trials as per standard
care. RESULTS: Smokers with schizophrenia who received COMB-EXT (with or without
HV) had greater reductions in cigarettes per day than those treated with TAU
(both ps < .01). In addition, 7-day point prevalence abstinence rates for the
three groups were 45%, 20%, and 8%, respectively, which was significantly higher
for COMB-EXT plus HV than TAU (chi2(1) = 4.8, p = .03). Groups did not differ
significantly in the number of adverse events, and HV were easily scheduled.
CONCLUSION: COMB-EXT improves outcomes for smokers with schizophrenia. HV
appeared to provide additional benefit for smoking cessation in this treatment
resistant population. IMPLICATIONS: The clear benefit found here of rapidly
initiated, combination, extended treatment over TAU suggests that aggressive and
extended treatment should be considered in clinical practice for smokers with
schizophrenia. Furthermore, HV to address SHS exposure showed initial promise for
assisting smokers with schizophrenia in maintaining abstinence, indicating that
this intervention may be worthy of future research.
PMID- 27613890
TI - Cigarette Smoking Behaviors and Beliefs in Persons Living With Hepatitis C.
AB - Background and Rationale: Tobacco use is common among persons living with
hepatitis C (PLHC), yet little is known about their smoking behaviors and
beliefs. Modern hepatitis C treatment offers a unique opportunity to intensively
engage this population about other health risks, including smoking. Main Results:
Seventy-seven tobacco users (40 hepatitis C virus [HCV] seropositive and 37 HCV
seronegative) enrolled in an interview study in a New York City clinic. The mean
age was 51.6, 57.1% were male, 40.3% Latino, and 49.4% black. 67.5% were single
and 18.2% were employed. HCV+ smokers differed from HCV- smokers in having a
higher prevalence of illicit substance use, depression, and hypertension. PLHC
smokers were highly motivated to quit, with 52.5% stating an intention to quit
within 30 days. Most of the PLHC smokers had used cessation-directed
pharmacotherapy, but almost none had tried a quitline or a quit smoking website.
PLHC smokers scored higher on the intrapersonal locus of control subscale. Almost
a quarter (22.5%) believed that smoking "helped fight the HCV." Conclusions: PLHC
smokers have a high burden of psychiatric and substance use comorbidity. They
exhibit characteristics that distinguish them from uninfected smokers, and many
harbor false beliefs about imagined benefits of smoking. They are highly
motivated to quit but underutilize cessation aids. Without aggressive
intervention, smoking-related morbidity will likely mute the health benefits and
longevity gains associated with hepatitis C treatment. Research such as this may
prove useful in guiding the development of future tobacco treatment strategies.
Implications: This is the first paper to examine, in detail, sociobehavioral
correlates of tobacco use in PLHC. PLHC are recognized by the Department of
Health and Human Services as a high-priority health disparities population. We
are not aware of any tobacco treatment services designed specifically for PLHC.
The first step in designing an intervention is defining the characteristics of
the target group. Our findings will begin to address this need, and may prove
useful in optimizing tobacco treatment strategies for smokers living with
hepatitis C.
PMID- 27613891
TI - Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute
Nicotine in Adult Contextual Fear Learning.
AB - INTRODUCTION: Adolescent onset of nicotine abuse is correlated with worse chances
at successful abstinence in adulthood. One reason for this may be due to enduring
learning deficits resulting from nicotine use during adolescence. Previous work
has indicated that chronic nicotine administration beginning in late adolescence
(PND38) caused learning deficits in contextual fear when tested in adulthood. The
purpose of this study was to determine if chronic nicotine treatment during
adolescence would alter sensitivity to nicotine's cognitive enhancing properties
in adulthood. METHODS: C57BL/6J mice received saline or chronic nicotine
(12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day
54) for a period of 12 days. Following a 30-day protracted abstinence, mice
received either an acute injection of saline or nicotine (0.045, 0.18, and
0.36mg/kg) prior to training and testing a mouse model of contextual fear.
RESULTS: It was found that chronic nicotine administration in adult mice did not
alter sensitivity to acute nicotine following a protracted abstinence. In
adolescent mice, chronic nicotine administration disrupted adult learning and
decreased sensitivity to acute nicotine in adulthood as only the highest dose
tested (0.36mg/kg) was able to enhance contextual fear learning. CONCLUSIONS:
These results suggest that adolescent nicotine exposure impairs learning in
adulthood, which could increase the risk for continued nicotine use in adulthood
by requiring administration of higher doses of nicotine to reverse learning
impairments caused by adolescent nicotine exposure. IMPLICATIONS: Results from
this study add to the growing body of literature suggesting chronic nicotine
exposure during adolescence leads to impaired learning in adulthood and
demonstrates that nicotine exposure during adolescence attenuates the cognitive
enhancing effects of acute nicotine in adulthood, which suggests altered
cholinergic function.
PMID- 27613892
TI - General Practitioners and Dentists: A Call for Action Against Tobacco.
AB - INTRODUCTION: To investigate the frequency of advice to quit smoking received by
the Italian population from general practitioners (GP) and dentists, we analyzed
a cross-sectional study. METHODS: A face-to-face survey was conducted in 2014 on
3052 individuals, representative of the general Italian population aged 15 years
or more. RESULTS: During the previous year, 89% of individuals (82% of smokers)
reported that they had visited a GP while 71% (67% of smokers) had visited a
dentist. Among smokers, 25% reported that they had received advice to quit
smoking from their GP, and 26% from their dentist. Advice by GPs was less
frequently received by smokers with higher education (multivariate odds ratios
(OR) were 0.48 for intermediate and 0.38 for high as compared to low education),
and more frequently by heavy smokers (>=15 cigarettes/day; OR = 1.78), those with
intention to quit (OR = 2.59), with previous quit attempts (OR = 2.09), and those
aware of the existence of smoking cessation services (OR = 1.59). Advice by
dentists was more frequently received by smokers aged 25-44 years (OR = 3.55
compared to those aged 15-24) and those with an intention to quit (OR = 2.46).
Among Italian current smokers, 32% reported that their GP and 17% that their
dentist was a current smoker. The corresponding figures among young smokers were
40% and 26%, respectively. CONCLUSION: Healthcare providers have the potential to
become a key reference point in the fight against smoking. However, before
acting, GPs and dentists should set a good example: those who smoke should
urgently quit or at least refrain from smoking during working hours.
IMPLICATIONS: GPs and dentists, reaching the large majority of Italian smokers,
can make a major contribution in the fight against tobacco. Future studies are
needed to investigate possible reasons of the apparently high smoking prevalence
among GPs, in order to develop tailored smoking cessation interventions for
healthcare providers.
PMID- 27613893
TI - Sex Differences in Smoking Cessation Pharmacotherapy Comparative Efficacy: A
Network Meta-analysis.
AB - Introduction: Converging clinical and biological evidence suggest sex is an
important factor when selecting a pharmacological intervention for smoking
cessation. The current investigation used network meta-analyses to estimate sex
differences in the comparative efficacy of transdermal nicotine (TN),
varenicline, and sustained release (SR) bupropion for smoking cessation. Methods:
Systematically searched previously published reviews and databases (Medline,
PsycINFO, Embase) of randomized, double-blind, placebo-controlled trials of
bupropion-SR, TN, and varenicline for cigarette smoking cessation in primary
care/general community samples were included. Results: Thirty-two studies met all
criteria and 28 (88%) were included in the final analyses, representing 14 389
smokers (51% female). Results of the full sample (women and men combined)
mirrored those from a Cochrane Tobacco Addiction Group network meta-analysis of
smoking cessation pharmacotherapy, showing VAR>TN=BUP. All medications improved
quit rates over placebo for both women and men. Relative to placebo, varenicline
efficacy was similar for women and men. Significant sex differences were evident
when comparing varenicline versus TN and varenicline versus bupropion. For women,
varenicline was more efficacious than TN (RR = 1.41; 95% CI = 1.12,1.76) and
bupropion (RR = 1.38; 95% CI = 1.08,1.77). For men, outcomes for those treated
with TN and bupropion were similar to those treated with varenicline. There were
no differences in efficacy when comparing bupropion versus TN. Conclusions: The
advantage of varenicline over bupropion SR and TN is greater for women than men.
Clinicians should strongly consider varenicline as the first option treatment for
women. Among men, the advantage of varenicline over TN or bupropion is less
clear. Implications: This study provides information for the sex-informed
treatment of nicotine addiction among cigarette smokers. Relative to placebo,
women and men achieved similar outcomes when treated with varenicline; however
the advantages of varenicline over transdermal patch and bupropion were greater
for women compared to men.
PMID- 27613894
TI - The Difference a Decade Makes: Smoking Cessation Counseling and Screening at
Pediatric Visits.
AB - INTRODUCTION: There has been a sharp decline in adolescents who smoke cigarettes
but no national-level study evaluating the impact of smoking cessation counseling
by pediatricians or other clinicians who care for children. METHODS: Combined
data from ambulatory portions of the National Hospital Ambulatory Care Survey and
National Ambulatory Medical Care Survey from 1997-1999 and 2009-2011 were
analyzed to determine changes in the frequency of pediatric visits that included
clinician-reported tobacco counseling and how such counseling varied by child,
family, and clinician characteristics. RESULTS: In 1997-1999, 1.5% of all medical
visits for children aged below 19 years included tobacco counseling; this
increased to 3.8% in 2009-2011 (P < .001). A marked increase from 4.1% to 11.1%
was noted at well-child visits (P < .001). There were significant increases in
counseling by pediatricians but not mid-level providers or general/family
physicians. Provision of counseling did not result in greater visit length during
either time point. During 2009-2011, visits with a diagnosis of asthma were four
times as likely (OR 4.2, 95% CI 2.8-6.2) and visits for otitis media two times as
likely (OR 2.1, 95% CI 1.2-3.7) to include smoking cessation counseling than sick
visits for all other diagnoses. CONCLUSION: These results demonstrate a
significant increase in tobacco counseling by pediatric providers within the last
decade, especially at well-child visits. However, the American Academy of
Pediatrics' recommendation that pediatricians counsel about the harms of tobacco
use and secondhand smoke exposure has not yet been exhaustively implemented.
IMPLICATIONS: A significant increase in smoking cessation counseling at pediatric
medical appointments, especially at well-child visits, occurred from 2009-2011
compared with 1997-1999, paralleling a large decrease in smoking prevalence.
These improvements in counseling rates have been predominantly noted for
pediatricians but not mid-level providers or general practitioners. Counseling
was not associated with increased visit lengths. Although improved counseling
practices by pediatricians have been demonstrated, there is still room for
improvement.
PMID- 27613896
TI - Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to
Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study.
AB - INTRODUCTION: Electronic cigarettes (e-cigarettes) are purported to deliver
nicotine aerosol without any toxic combustion products present in tobacco smoke.
In this longitudinal within-subjects observational study, we evaluated the
effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens
and toxicants. METHODS: We measured seven nicotine metabolites and 17 tobacco
smoke exposure biomarkers in the urine samples of 20 smokers collected before and
after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were
metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco
specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene,
crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and
propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene,
fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration
were tested using repeated measures analysis of variance. RESULTS: In total, 45%
of participants reported complete abstinence from cigarette smoking at 2 weeks,
while 55% reported continued smoking. Levels of total nicotine and some
polycyclic aromatic hydrocarbon metabolites did not change after switching from
tobacco to e-cigarettes. All other biomarkers significantly decreased after 1
week of using e-cigarettes (p < .05). After 1 week, the greatest percentage
reductions in biomarkers levels were observed for metabolites of 1,3-butadiene,
benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and
64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by
46% at week 1, and 34% at week 2. CONCLUSIONS: After switching from tobacco to e
cigarettes, nicotine exposure remains unchanged, while exposure to selected
carcinogens and toxicants is substantially reduced. IMPLICATIONS: To our
knowledge, this is the first study that demonstrates that substituting tobacco
cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and
carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to
harmful constituents that are present in tobacco cigarettes and e-cigarettes can
aid in evaluating e-cigarettes as a potential harm reduction device.
PMID- 27613897
TI - Protective Effect of Nicotine on Sepsis-Induced Oxidative Multiorgan Damage: Role
of Neutrophils.
AB - Introduction: Despite its adverse health consequences, tobacco smoking is
associated with lower incidence of several neurodegenerative and inflammatory
diseases. The present study is aimed to show the effects of nicotine, major
tobacco constituent, on five organs targeted by sepsis. Methods: Male Wistar
albino rats received tap water with (5mg/kg) or without nicotine for 14 days.
Under ketamine anesthesia, sepsis (n = 50) was induced by ligation and puncture
of the cecum, while sham group (n = 8) had only laparotomy. In other rats,
nicotine drink was withdrawn for 5 days before sepsis induction, while in acute
nicotine group, rats were injected with nicotine (30mg/kg, i.p.) before sepsis,
but had no oral intake. Rats were decapitated 24 hours after surgery to obtain
lung, liver, ileum, heart, and kidney tissues to determine malondialdehyde (MDA)
and glutathione (GSH) levels and myeloperoxidase (MPO) activities. Data were
analyzed by one-way analysis of variance and Tukey multiple comparison tests or
Student's t test. Results: Chronic nicotine administration or its withdrawal
reduced lipid peroxidation and MPO activity and prevented GSH depletion with some
varying results in different target tissues. Nicotine injection prior to sepsis
depressed MPO activity in all tissues and reduced MDA levels except for the lung,
while GSH levels were elevated only in the hepatic and ileal tissues.
Histologically observed injury was ameliorated by all nicotine treatments at
varying degrees. Conclusions: The findings of the present study indicate that
long-term nicotine administration reduces sepsis-induced oxidative damage in
several tissues, which appears to involve inhibition of neutrophil activity in
the inflamed tissues. Implications: Nicotine administration or its withdrawal
reduced lipid peroxidation and neutrophil content and prevented GSH depletion
with some varying results in different target tissues. A single injection prior
to sepsis induction depressed MPO activity in all the tissues and reduced all
tissue MDA levels except for the lung. When nicotine was withdrawn for 5 days,
its inhibitory effect on MPO activity was still present in all the tissues except
for the liver. Microscopically an improved inflammatory response was observed in
all the tissues of rats that have received different nicotine pretreatment
regimens.
PMID- 27613898
TI - Access to Subsidized Smoking Cessation Medications by Australian Smokers Aged 45
Years and Older: A Population-Based Cohort Study.
AB - Introduction: The principal aim of this study was to assess the accessibility of
subsidized cessation medications to socioeconomically disadvantaged smokers,
including smokers living in regional and remote communities. Methods: Analyses
used baseline questionnaire and linked Pharmaceutical Benefits Scheme data for 18
686 regular smokers participating in the 45 and Up Study, a large-scale
Australian cohort study of people aged 45 years and older. Participants who were
dispensed nicotine replacement therapy, varenicline, or bupropion were identified
from the Pharmaceutical Benefits Scheme data, which provide an essentially
complete record of participants' access to subsidized pharmaceuticals.
Associations between the supply of each pharmacotherapy and a range of
sociodemographic and health-related variables were evaluated using multiple
logistic regression. Results: The odds that participants were supplied with a
cessation medication declined markedly with increasing age for participants older
than 60 years and were substantially higher for participants who smoked 20 or
more cigarettes/day than for participants who smoked fewer than 10
cigarettes/day. Participants with no formal qualification and those residing in
socioeconomically disadvantaged areas had higher odds of receiving nicotine
replacement therapy or varenicline than university-educated participants and
participants living in the least disadvantaged areas. There was no evidence that
participants residing in regional and remote communities had lower odds of
receiving a cessation medication than participants residing in major cities.
Conclusions: Older Australian smokers' access to cessation pharmacotherapies is
determined predominantly by age and daily cigarette consumption and does not
appear to be limited by educational achievement, socioeconomic disadvantage, or
remoteness. Implications: Promoting the use of cessation medications is a
principal measure proposed to achieve Australia's National Tobacco Strategy 2012
2018 goal of reducing cigarette consumption among socioeconomically disadvantaged
smokers. The results of this large-scale cohort study indicate that access to
cessation pharmacotherapies is determined primarily by age and daily cigarette
consumption, and is not limited by socioeconomic circumstances, providing some
reassurance that existing government subsidies are sufficient to ensure that
pharmaceutical aids are accessible to all Australian smokers.
PMID- 27613895
TI - Examination of the Involvement of Cholinergic-Associated Genes in Nicotine
Behaviors in European and African Americans.
AB - Introduction: Cigarette smoking is a physiologically harmful habit. Nicotinic
acetylcholine receptors (nAChRs) are bound by nicotine and upregulated in
response to chronic exposure to nicotine. It is known that upregulation of these
receptors is not due to a change in mRNA of these genes, however, more precise
details on the process are still uncertain, with several plausible hypotheses
describing how nAChRs are upregulated. We have manually curated a set of genes
believed to play a role in nicotine-induced nAChR upregulation. Here, we test the
hypothesis that these genes are associated with and contribute risk for nicotine
dependence (ND) and the number of cigarettes smoked per day (CPD). Methods:
Studies with genotypic data on European and African Americans (EAs and AAs,
respectively) were collected and a gene-based test was run to test for an
association between each gene and ND and CPD. Results: Although several novel
genes were associated with CPD and ND at P < 0.05 in EAs and AAs, these
associations did not survive correction for multiple testing. Previous
associations between CHRNA3, CHRNA5, CHRNB4 and CPD in EAs were replicated.
Conclusions: Our hypothesis-driven approach avoided many of the limitations
inherent in pathway analyses and provided nominal evidence for association
between cholinergic-related genes and nicotine behaviors. Implications: We
evaluated the evidence for association between a manually curated set of genes
and nicotine behaviors in European and African Americans. Although no genes were
associated after multiple testing correction, this study has several strengths:
by manually curating a set of genes we circumvented the limitations inherent in
many pathway analyses and tested several genes that had not yet been examined in
a human genetic study; gene-based tests are a useful way to test for association
with a set of genes; and these genes were collected based on literature review
and conversations with experts, highlighting the importance of scientific
collaboration.
PMID- 27613899
TI - How US Smokers Refer to E-cigarettes: An Examination of User-Generated Posts From
a Web-Based Smoking Cessation Intervention, 2008-2015.
AB - INTRODUCTION: A challenge in Electronic Nicotine Delivery System (ENDS) research
is how to refer to these devices in ways that are meaningful to current or
potential users. The objectives of this study were to: (1) describe the frequency
of ENDS terms in a web-based smoking cessation intervention; and (2) determine
whether terms vary by US geographic region and date. METHODS: Data were drawn
from public posts between 2008-2015 on http://BecomeAnEX.org and limited to US
users. We conducted "exact" and "fuzzy" searches to find posts containing ENDS
keywords using custom Python scripts, and extracted geocoding data and date for
each post. We examined counts and frequencies of ENDS terms by unique user, by
unique user and region, and by unique user and date. RESULTS: We identified 1023
unique US website users who had written a post containing one or more ENDS
keywords. Posters were majority female (79%), educated (78% attended at least
some college), and had a median age of 47 years. Overall, 92% of ENDS posters
employed the term "e-cigarette" or a derivation. Derivations of "vape" became
increasingly popular in 2013, whereas "NJoy" and "blu" were employed by fewer
than 2% of posters. We found no variation in frequency of ENDS terms by US
region. CONCLUSIONS: Researchers may have confidence that "e-cigarette" and
"vape" are recognizable terms among US treatment-seeking smokers. Conversely,
terms such as "ENDS," commonly employed by researchers and public health
advocates, are not used by smokers and may be an impediment to tobacco control
research. IMPLICATIONS: Researchers may have confidence that "e-cigarette," and,
to a lesser extent, "vape" are recognizable terms among US adult smokers
referring to ENDS (including accessories, brand names, and actions). Conversely,
terms such as "electronic nicotine delivery systems," commonly employed by
researchers and public health advocates, are not used by US smokers and may be an
impediment to tobacco control research and practice.
PMID- 27613900
TI - Reducing Disparities in Tobacco Retailer Density by Banning Tobacco Product Sales
Near Schools.
AB - INTRODUCTION: This study examined whether a policy of banning tobacco product
retailers from operating within 1000 feet of schools could reduce existing
socioeconomic and racial/ethnic disparities in tobacco retailer density. METHODS:
We geocoded all tobacco retailers in Missouri (n = 4730) and New York (n = 17
672) and linked them with Census tract characteristics. We then tested the
potential impact of a proximity policy that would ban retailers from selling
tobacco products within 1000 feet of schools. RESULTS: Our results confirmed
socioeconomic and racial/ethnic disparities in tobacco retailer density, with
more retailers found in areas with lower income and greater proportions of
African American residents. A high proportion of retailers located in these areas
were in urban areas, which also have stores located in closer proximity to
schools. If a ban on tobacco product sales within 1000 feet of schools were
implemented in New York, the number of tobacco retailers per 1000 people would go
from 1.28 to 0.36 in the lowest income quintile, and from 0.84 to 0.45 in the
highest income quintile. In New York and Missouri, a ban on tobacco product sales
near schools would either reduce or eliminate existing disparities in tobacco
retailer density by income level and by proportion of African American.
CONCLUSIONS: Proximity-based point of sale (POS) policies banning tobacco product
sales near schools appear to be more effective in reducing retailer density in
lower income and racially diverse neighborhoods than in higher income and white
neighborhoods, and hold great promise for reducing tobacco-related disparities at
the POS. IMPLICATIONS: Given the disparities-reducing potential of policies
banning tobacco product sales near schools, jurisdictions with tobacco retailer
licensing should consider adding this provision to their licensing requirements.
Since relatively few jurisdictions currently ban tobacco sales near schools,
future research should examine ways to increase and monitor the uptake of this
policy, and assess whether it has an impact upon reducing exposure to tobacco
marketing and on tobacco product availability and use.
PMID- 27613901
TI - A Randomized Trial of Adjunct mHealth Abstinence Reinforcement With Transdermal
Nicotine and Counseling for Smoking Cessation.
AB - Introduction: Abstinence reinforcement is efficacious for improving smoking
treatment outcomes, but practical constraints related to the need for multiple in
person carbon monoxide (CO) breath tests daily to verify smoking abstinence have
limited its use. This study tested an mHealth procedure to remotely monitor and
reinforce smoking abstinence in individuals' natural environment. Methods:
Eligible treatment-seeking smokers (N = 90) were randomized to (1) usual care and
ecological monitoring with abstinence reinforcement (mHealth reinforcement) or
(2) without reinforcement (mHealth monitoring). Usual care was 8 weeks of
transdermal nicotine and twice-weekly telephone counseling. Following training,
an interactive voice response system prompted participants to conduct CO tests 1
3 daily at pseudorandom times (7 am to 10 pm) for 4 weeks. When prompted,
participants used a study cell phone and CO monitor to complete a CO self-test,
video record the process, and submit videos using multimedia messaging. mHealth
reinforcement participants could earn prizes for smoking-negative on-time CO
tests. The interactive voice response generated preliminary earnings immediately.
Earnings were finalized by comparing video records against participants' self
reports. Results: mHealth reinforcement was associated with a greater proportion
of smoking-negative CO tests, longest duration of prolonged abstinence, and point
prevalence abstinence during the monitoring/reinforcement phase compared to
mHealth monitoring (p < .01, d = 0.8-1.3). Follow-up (weeks 4-24) analyses
indicated main effects of reinforcement on point-prevalence abstinence and
proportion of days smoked (p <= .05); values were comparable by week 24.
Conclusions: mHealth reinforcement has short-term efficacy. Research on methods
to enhance and sustain benefits is needed. Implications: This study suggests that
mHealth abstinence reinforcement is efficacious and may present temporal and
spatial opportunities to research, engage, and support smokers trying to quit
that do not exist with conventional (not technology-based) reinforcement
interventions.
PMID- 27613903
TI - Factors Associated With Accepting Assistance for Smoking Cessation Among Military
Veterans.
AB - INTRODUCTION: Cigarette smoking remains a significant health risk for Veterans.
Increased understanding of factors that influence the tobacco cessation referral
process within Veterans Affairs medical facilities is useful for enhancing
utilization of smoking cessation treatment. The present study examined the
association of demographic and health variables with whether smokers accepted
referral for medication and/or tobacco cessation clinic. METHODS: Electronic
medical record data (2011-2013) were obtained for a sample of US military
Veterans who accepted cessation assistance from their health care provider.
Demographic and diagnostic variables were examined to identify predictors of the
types of assistance accepted (medication only, clinic referral only, or both).
RESULTS: The sample includes 2941 Veterans, 10.3% female, 19.9% African American,
10.7% Hispanic, and 57.9% non-Hispanic white. Veterans averaged of 50.69 years of
age (SD = 14.01), 31.5% had a substance use disorder diagnosis and 54.1% had a
psychiatric diagnosis. Demographic and diagnostic information was compared across
types of assistance accepted. Significant differences were found between those
who accepted medications only and those who accepted either clinic referral or
both medication and clinic referral. Veterans in the latter two categories were
younger and more likely to have a psychiatric diagnosis than those accepting
medication only. Women Veterans were significantly more likely than men to accept
clinic referral plus medication. However, in contrast to men, almost none of the
variables examined were associated with the type of assistance accepted by women.
CONCLUSION: These findings indicate significant gender differences in influences
on accepting assistance for smoking cessation among Veterans. IMPLICATIONS:
Existing research identifies factors associated with unassisted quitting.
However, little is known regarding the referral process, which is critical in
connecting smokers with treatment. The present work is unique in employing
electronic medical record data to examine factors associated with accepting
different types of smoking cessation treatment referrals. This study represents
an initial effort to elucidate the smoking cessation treatment referral process.
These findings highlight the need to examine sex specific influences on smoking
cessation treatment utilization and the importance of focusing on smokers with
psychiatric disorders.
PMID- 27613902
TI - Effects of Enactment of Legislative (Public) Smoking Bans on Voluntary Home
Smoking Restrictions: A Review.
AB - INTRODUCTION: The positive effects of worldwide increases in enactment of
legislative bans on smoking in public areas have been well documented. Relatively
little is known about the effects of such bans on voluntary home smoking
behavior. Meanwhile, private spaces, such as homes, have replaced public spaces
as the primary milieu of secondhand smoke exposure. METHODS: A systematic search
of peer-reviewed articles was conducted using multiple databases including
Cochrane Library, Cinahl, Embase, Global Health, Health Star, Joanna Briggs,
MEDLINE, PsycINFO, PAIS International, PubMed, and Web of Science. We examined
peer-reviewed studies that considered the impact of legislation-based public
smoking bans on enactment of private home smoking restrictions. RESULTS: Sixteen
articles published between 2002 and 2014 were identified and included. Our
results suggest overall positive effects post-legislative ban with the majority
of studies demonstrating significant increases in home smoking restrictions.
Studies focusing on smoking and nonsmoking samples as well as child populations
are discussed in depth. CONCLUSIONS: Existing evidence indicates an overall
significant positive effect post-legislative ban on voluntary home smoking
restrictions. While disentangling these effects over space and time remains a
challenge, scientific research has converged in dispelling any notion of
significant displacement of smoking into the home. Policy makers, especially
those in countries without existing public smoking legislation, can rest assured
that these types of bans contribute to the minimization of tobacco-related harm.
IMPLICATIONS: Findings converge in dispelling notions of displacement of smoking
into the home as a consequence of legislative bans that prohibit smoking in
public spaces. Evidence from the studies reviewed suggests that through their
influence on social norms, legislative bans on smoking in public places may
encourage citizens to establish voluntary home smoking restrictions, thus
decreasing harm related to secondhand smoke.
PMID- 27613904
TI - The Short Form Vaping Consequences Questionnaire: Psychometric Properties of a
Measure of Vaping Expectancies for Use With Adult E-cigarette Users.
AB - INTRODUCTION: E-cigarettes are popular in the United States, but psychometrically
sound measures of vaping beliefs and behaviors are lacking. METHODS: We evaluated
the psychometrics of the Short Form Vaping Consequences Questionnaire (S-VCQ), a
modified version of the Short Form Smoking Consequences Questionnaire that
assesses expectancies for negative consequences, positive reinforcement, negative
reinforcement, and appetite/weight control associated with vaping. Adult, past
month e-cigarette users completed an anonymous survey in Fall 2015 (N = 522,
50.4% female; 71.5% white; 34.10 [SD = 9.66] years). Psychometric analyses
included confirmatory factor analysis, internal consistency, measurement
invariance, t tests, correlations, and test-criterion relationships with vaping
outcomes. RESULTS: The S-VCQ evidenced a four-factor latent structure (Bentler's
Comparative Fit Index = .95, Root Mean Square Error of Approximation = .05,
Standardized Root Mean Square Residual = .06), and subscales evidenced internal
consistency (mean alpha = 0.89). S-VCQ scores were scalar invariant for sex and
smoking status; women reported stronger appetite/weight control than men and dual
cigarette/e-cigarette users (n = 309) reported stronger negative vaping
consequences and negative reinforcement than nonsmokers. Among dual users, vaping
and smoking expectancies also were scalar invariant; dual users reported stronger
positive reinforcement associated with vaping than smoking but stronger negative
consequences, negative reinforcement, and appetite/weight control associated with
smoking than vaping. Correlations indicated that vaping and smoking expectancies
were related, yet distinct constructs. Univariate general linear models indicated
that vaping frequency and dependence were associated with positive reinforcement
(etap2 = .02/.02), negative reinforcement (etap2 = .02/.08), and appetite/weight
control (etap2 = .02/.02) from vaping. CONCLUSIONS: The S-VCQ evidences solid
psychometrics as a measure of adult e-cigarette users' vaping expectancies.
IMPLICATIONS: The current study provides evidence for the reliability and
validity of the S-VCQ, the first measure of vaping expectancies that has been
validated for use with adult e-cigarette users. Results indicated that the S-VCQ
comprises four subscales that evidence internal consistency, scalar measurement
invariance for important groups of interest, and test-criterion relationships
with vaping outcomes. Researchers are encouraged to consider using this measure
for assessing vaping expectancies in adult e-cigarette users.
PMID- 27613905
TI - Barriers and Facilitators to Smoking Cessation Among People With Severe Mental
Illness: A Critical Appraisal of Qualitative Studies.
AB - BACKGROUND: People with severe mental illness (PWSMI) die 15-20 years earlier
than people in the general population and this is often due to preventable
smoking-related health conditions. Studies that identify barriers and
facilitators to smoking cessation are crucial for policy makers and health care
professionals. AIMS: This appraisal aims to identify and critically appraise
qualitative studies which explore smoking experiences and barriers to smoking
cessation among PWSMI. METHOD: Articles were retrieved from electronic health
related databases including Web of Science, Scopus, PubMed, Sage, Biomed,
Medline, Embase, and electronic hand searches of bibliographies from key
articles. RESULTS: Eleven papers were identified. Although the overall quality of
studies were sufficient, most had limited information relating to trustworthiness
and sociodemographic details. Cost savings and health benefits were frequently
cited as facilitators to quitting, however may be of limited impact as smoking
for existential purposes, social inclusion, and mental health management appear
to be considered highly important among PWSMI. CONCLUSIONS: Findings were
restricted to predominantly individual barriers to smoking cessation which may be
more resistant to change as service users rely on smoking to manage their mental
health and smoking is embedded in the culture of mental health settings.
IMPLICATIONS: This critical appraisal identifies qualitative evidence regarding
which factors facilitate or prevent individuals with severe mental illness from
engaging with smoking cessation. Healthcare professionals and policy makers
should address external barriers to quitting smoking as this may increase
participation in intervention studies, inform policy and assist in the
development of a feasible and acceptable smoking cessation intervention among
PWSMI. Methodological considerations highlight that future research should
include sociodemographic and contextual factors to improve utility and
applicability of findings.
PMID- 27613906
TI - Using Self-affirmation to Increase the Effects of Emotive Health Warnings on
Smoking: A Randomized Exploratory Trial.
AB - Introduction: Emotive health messages are widely used tools in tobacco control.
However, under some circumstances, they can be less effective than desired by
eliciting defensive responses in smokers. Aims: This study tests whether
enhancing a currently used emotive graphic smoking health warning with a self
affirmation component reduces cigarette consumption and whether potential effects
are stronger in heavier smokers, as suggested by previous research. Methods:
Participants (n = 265) were randomly allocated to a self-affirmation (reflecting
on personal values and positive traits using a questionnaire) or matched control
condition before viewing an emotive graphic health message from a current
Australian government public health campaign. The primary outcome (cigarettes per
day [CPD]) was assessed both before and a week following the intervention.
Results: No main effect of self-affirmation on smoking, but as hypothesized, a
significant interaction between baseline smoking and self-affirmation was found
that showed that heavier smokers (>21 CPD) who self-affirmed significantly
reduced CPD compared to nonaffirmed smokers. Conclusions: These findings support
the use of self-affirmation to enhance smoking awareness campaigns in heavier
smokers. Implications: This study shows that enhancing emotive graphic smoking
health messages with self-affirmation (the act of reflecting on positive aspects
of oneself) increases their effectiveness in heavier smokers. This suggests that
self-affirmation might be a particularly useful tool for health promotion
targeting heavier smokers. This study adds to previous research in that it is the
first to test the add-on effects of self-affirmation to current graphic health
messages on smoking rather than smoking-related cognitions.
PMID- 27613907
TI - Secondhand Tobacco Smoke Exposure Associations With DNA Methylation of the Aryl
Hydrocarbon Receptor Repressor.
AB - Introduction: Cigarette smoking is inversely associated with DNA methylation of
the aryl hydrocarbon receptor repressor (AHRR; cg05575921). However, the
association between secondhand tobacco smoke (SHS) exposure and AHRR methylation
is unknown. Methods: DNA methylation of AHRR cg05575921 in CD14+ monocyte
samples, from 495 never-smokers and 411 former smokers (having quit smoking >=15
years) from the Multi-Ethnic Study of Atherosclerosis (MESA), was cross
sectionally compared with concomitantly ascertained self-reported SHS exposure,
urine cotinine concentrations, and estimates of air pollutants at participants'
homes. Linear regression was used to test for associations, and covariates
included age, sex, race, education, study site, and previous smoking exposure
(smoking status, time since quitting, and pack-years). Results: Recent indoor SHS
exposure (hours per week) was inversely associated with cg05575921 methylation
(beta +/- SE = -0.009 +/- 0.003, p = .007). The inverse effect direction was
consistent (but did not reach significance) in the majority of stratified
analyses (by smoking status, sex, and race). Categorical analysis revealed high
levels of recent SHS exposure (>=10 hours per week) inversely associated with
cg05575921 methylation (beta +/- SE = -0.28 +/- 0.09, p = .003), which remained
significant (p < .05) in the majority of stratified analyses. cg05575921
methylation did not significantly (p < .05) associate with low to moderate levels
of recent SHS exposure (1-9 hours per week), urine cotinine concentrations, years
spent living with people smoking, years spent indoors (not at home) with people
smoking, or estimated levels of air pollutants. Conclusions: High levels of
recent indoor SHS exposure may be inversely associated with DNA methylation of
AHRR in human monocytes. Implications: DNA methylation is a biochemical
alteration that can occur in response to cigarette smoking; however, little is
known about the effect of SHS on human DNA methylation. In the present study, we
evaluated the association between SHS exposure and DNA methylation in human
monocytes, at a site (AHRR cg05575921) known to have methylation inversely
associated with current and former cigarette smoking compared to never smoking.
Results from this study suggest high levels of recent SHS exposure inversely
associate with DNA methylation of AHRR cg05575921 in monocytes from nonsmokers,
albeit with weaker effects than active cigarette smoking.
PMID- 27613908
TI - Racial/Ethnic Differences in Self-reported Withdrawal Symptoms and Quitting
Smoking Three Years Later: A Prospective, Longitudinal Examination of US Adults.
AB - Introduction: Racial/ethnic groups appear to differ on quit success and
withdrawal is a key factor in cessation failure, yet little is known about
racial/ethnic differences in withdrawal symptoms. This study of US adults
examined racial/ethnic differences in current smokers' report of withdrawal
symptoms and the relationship between withdrawal symptoms and quitting smoking 3
years later. Methods: Using data from the National Epidemiologic Survey on
Alcohol and Related Conditions (Wave 1, 2001-2001; Wave 2, 2004-2005), analyses
were conducted on participants who identified as non-Hispanic White, non-Hispanic
Black, or Hispanic; reported current cigarette smoking at Wave 1; and provided
smoking status information at Wave 2 (n = 7981). Withdrawal symptoms during past
quit attempts were assessed at Wave 1. Results: Among Wave 1 current smoking
adults, non-Hispanic White respondents were more likely than non-Hispanic Black
and Hispanic respondents to report experiencing at least one withdrawal symptom,
seven out of eight withdrawal symptoms, withdrawal-related discomfort, and
withdrawal-related distress (ps < .0001). While withdrawal symptoms were
associated with a lower odds of quitting smoking for all groups, a stronger
relationship between number of symptoms and lower odds of quitting was evident
among non-Hispanic White compared to non-Hispanic Black respondents (interaction
beta = 0.065, p = .0001). For non-Hispanic White participants, each additional
withdrawal symptom was associated with a 6% decrease in the odds of quitting.
Conclusions: Withdrawal symptoms were more commonly reported by non-Hispanic
White adults than non-Hispanic Black and Hispanic adults and appeared to have a
greater impact on failure to quit smoking for non-Hispanic White compared to non
Hispanic Black adults. Implications: To our knowledge, this is the first study to
use prospective, longitudinal data to examine the relationship between race and
withdrawal symptoms and the impact of withdrawal symptoms on quitting smoking
among adults in the United States. Non-Hispanic White adults were more likely to
report withdrawal symptoms and there was a stronger relationship between greater
number of withdrawal symptoms and lower odds of quitting for non-Hispanic White
adults compared to non-Hispanic Black adults. Developing a better understanding
of racial/ethnic differences in withdrawal and cessation can help to tailor
efforts to improve outcomes for smokers in various racial/ethnic groups.
PMID- 27613909
TI - Smoking Cessation Programs for Lesbian, Gay, Bisexual, Transgender, and Intersex
People: A Content-Based Systematic Review.
AB - Introduction: Tobacco use among lesbian, gay, bisexual, and transgender (LGBT)
people is double the general population. Limited evidence suggests high smoking
rates among intersex people. Lesbian, gay, bisexual, transgender, and intersex
(LGBTI) people are a priority population in Australian health policy,
particularly mental health and aging. Despite associations between smoking and
noncommunicable diseases relevant to aging and mental health, LGBTI-targeted
smoking cessation interventions in Australia have been limited to people living
with HIV. Applying existing interventions to marginalized populations without
modification and evaluation may fail and exacerbate inequities. Aims: To assess
outcomes and characterize the populations served, cultural modifications, and
behavior change techniques (BCTs) of interventions to reduce LGBTI smoking.
Methods: We searched MEDLINE, six additional databases, and contacted authors to
retrieve published and unpublished program evaluations. Results: We retrieved 19
studies (3663 participants). None used control groups. Overall quit rate was
61.0% at the end of interventions and stabilized at 38.6% at 3-6 months. All
studies included gay men, 13 included lesbians, 13 "LGBT," 12 bisexual people,
five transgender people, and none included intersex people. Transgender people
comprised 3% of participants. Of programs open to women, 27.8% of participants
were women. Cultural modifications were used by 17 (89.5%) studies, commonly
meeting in LGBT spaces, discussing social justice, and discussing LGBT-specific
triggers. Common BCTs included providing normative information, boosting
motivation/self-efficacy, relapse prevention, social support, action planning,
and discussing consequences. Conclusions: Quit rates were high; using control
groups would improve evaluation. Existing programs may fail to reach groups other
than gay men. Implications: This review examines the evidence for LGBTI-targeted
smoking cessation interventions. Populations within LGBTI are not proportionally
represented in smoking cessation research, and no study addressed intersex
smoking. Overall, LGBT-targeted interventions appear to be effective, and simply
having an LGBT-specific group may be more effective than groups for the general
population. More rigorous research is necessary to draw firm conclusions. Our
study space analysis provides suggestions for areas of more targeted research on
mechanisms underlying these complex interventions' success.
PMID- 27613910
TI - Development of a Measure of Incremental Behavior Change Toward Smoking Cessation.
AB - Introduction: A reliable measure capable of detecting progression towards smoking
cessation would be valuable for evaluating and optimizing the effectiveness of
low- to moderate-intensity cessation interventions, such as brief advice in the
primary care setting. This article presents the development and evaluation of a
brief self-report measure of Incremental Behavior Change toward Smoking cessation
(IBC-S). Methods: Sequential samples of 411 and 399 adult smokers completed items
representing a spectrum of behavioral and cognitive changes antecedent to smoking
cessation. The dimensionality, fit, range of difficulty, and reliability of items
were evaluated using factor analysis and Rasch modeling. Results: The final 15
item IBC-S measure met fit criteria and demonstrated acceptable reliability.
Participants with a significant change in IBC-S score were over four times more
likely to report cessation at 6-week follow-up (OR 4.37, 95% CI 1.83-10.42).
Conclusion: The IBC-S is brief, reliable and associated with self-report of
smoking reduction and cessation. Implications: This article presents the
psychometric evaluation of a measure to assess a spectrum of behaviors and
cognitions antecedent to smoking cessation. The findings indicate that the items
show good measurement properties and good potential as a sensitive measure to
evaluate interventions. This measure provides an alternative outcome for
interventions that are designed to move individuals towards cessation attempts.
PMID- 27613912
TI - Smoking Cessation and Changes in Body Mass Index: Findings From the First
Randomized Cessation Trial in a Low-Income Country Setting.
AB - Background: In high-income countries, quitting cigarette smoking is associated
with weight gain, which can reduce motivation to abstain. Whether smoking
cessation is associated with weight gain in a low-income country context has
never been investigated. We aimed to determine the post-cessation changes in body
mass index (BMI) and its predictors among smokers who received a smoking
cessation intervention in a low-income country setting. Methods: We performed
post hoc analyses of data from 269 smokers who participated in a two-group,
parallel-arm, double-blind, placebo-controlled randomized trial of combined
nicotine replacement therapy (NRT) and behavioral counseling in primary care
clinics in Aleppo, Syria. We used generalized estimating equation modeling to
identify predictors of changes in BMI at 6 weeks and 6- and 12-month follow-ups
after quit date. Results: The mean pre-cessation BMI of the sample was 27.9kg/m2
(SD = 5.2). Over 12 months of follow-up, BMI of smoking abstainers averaged 1.8
BMI units (approximately 4.8kg) greater than non-abstainers (p = .012).
Throughout the study, greater BMI was associated with being female (p = .048),
reporting smoking to control weight (p < .001) and having previously failed to
quit due to weight gain (p = .036). Conclusion: Similar to findings from high
income countries, smoking cessation in Syria is associated with weight gain,
particularly among women and those who have weight concerns prior to quitting.
This group of smokers may benefit from tailored cessation interventions with
integrated body weight management elements that take into consideration the
prevailing local and cultural influences on diet and levels of physical activity.
Implications: This study provides the first evidence regarding post-cessation
changes in BMI among smokers who attempt to quit in a low-income country setting.
Our findings advance knowledge regarding post-cessation weight gain and offers
insight for researchers and clinicians to identify smokers at higher risk of post
cessation weight gain. This information will help in delivering interventions
that take into account the prevailing cultural influence on diet and physical
activity and will ultimately help in designing future tailored cessation programs
in Syria and other low-income countries with similar cultural background and
level of development.
PMID- 27613911
TI - Concurrent E-Cigarette Use During Tobacco Dependence Treatment in Primary Care
Settings: Association With Smoking Cessation at Three and Six Months.
AB - INTRODUCTION: Electronic cigarettes (e-cigarettes) are being used as cessation
aids by many smokers despite a lack of empirical evidence regarding their safety
and efficacy. We analyzed the association of e-cigarette use and smoking
abstinence in a population of smokers accessing standard smoking cessation
treatment (nicotine replacement therapy [NRT] plus behavioral counseling) through
primary care clinics in Ontario, Canada. METHODS: Participants were recruited
through 187 primary care clinics across Ontario, Canada and were eligible for up
to 26 weeks of brief behavioral counseling and individualized dosing of NRT at no
cost. Adjusted logistic regression models were used to examine the association
between concurrent e-cigarette use and smoking abstinence at 3- and 6-month
follow-ups. RESULTS: Of the 6526 participants who completed a 3-month follow-up,
18.1% reported using an e-cigarette while in treatment. The majority of e
cigarette users (78.2%) reported using an e-cigarette for smoking cessation. At 3
month follow-up, e-cigarette use was negatively associated with abstinence after
controlling for confounders (adjusted odds ratio [AOR] = 0.706, p < .001, 95%
confidence interval [CI] = 0.607-0.820). E-cigarette use was also negatively
associated with abstinence at 6-month follow-up (AOR = 0.502, p < .001, 95% CI =
0.393-0.640). CONCLUSION: E-cigarette use was negatively associated with
successful quitting in this large community sample of smokers accessing standard
evidence-based smoking cessation treatment through primary care clinics, even
after adjusting for covariates such as severity of tobacco dependence, gender,
and age. The findings suggest that concurrent use of e-cigarettes with NRT may
harm cessation attempts. IMPLICATIONS: This study confirms previous findings from
observational studies regarding the negative association between e-cigarette use
and smoking cessation, but in a large cohort of smokers enrolled in an evidence
based treatment program. The implications of these findings are that concurrent
use of e-cigarettes during a quit attempt utilizing cost-free evidence-based
treatment (NRT plus behavioral counseling) does not confer any added benefit and
may hamper successful quitting.
PMID- 27613913
TI - Postpartum Smoking Relapse and Breast Feeding: Defining the Window of Opportunity
for Intervention.
AB - Background: Though many women spontaneously quit smoking during pregnancy, a
large proportion relapse after delivery. Efforts aimed at reducing postpartum
smoking relapse have been largely ineffective. Several studies have reported
breast feeding as a primary factor influencing smoking abstinence duration.
However, data on the potential role of breast feeding in smoking intervention
efforts remain incomplete. Methods: The Ulm SPATZ Health Study cohort consists of
1006 newborns of 970 mothers recruited in the University Medical Center Ulm,
Germany. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models
were used to assess differences in predominant and total breast-feeding duration
stratified by smoking abstinence at 2 years and relapse period (by 6 weeks, 6
months, and 2 years postdelivery). Chi-square and Kruskal-Wallis tests were
performed to identify significant differences in demographic and lifestyle
factors across smoking categories. Results: Approximately 70% of previous smokers
who initiated breast feeding relapsed within 2 years. Relapse by 6 months was
significantly associated with noninitiation of predominant breast feeding. Total
breast-feeding duration rates among abstaining mothers and those who relapsed
after 6 weeks mirrored those of nonsmokers respectively up to 1 year and 3
months. Lower age and education were mostly associated with smoking by 6 weeks.
First parity and having a nonsmoking partner were associated with abstinence up
to 2 years. Conclusions: Interventions promoting breast feeding to incentivize
continued smoking abstinence may be effective prior to weaning. Those promoting
breast feeding longer than 6 months and partner smoking cessation may increase
rates of long-term smoking abstinence lasting longer than 2 years postdelivery.
Implications: Most mothers who quit smoking during pregnancy relapse within 6
months of delivery. Though interventions targeting new mothers have been largely
unsuccessful, relapse is often delayed until after weaning and targeted breast
feeding promotion has been suggested to enhance smoking cessation interventions.
In this study, we assess the relationship between breast-feeding duration and
long-term smoking abstinence by longitudinally investigating predominant and
total breast-feeding patterns among mothers with a recent history of smoking
stratified by period of relapse up to 2 years after delivery.
PMID- 27613914
TI - The Influence of a Mouthpiece-Based Topography Measurement Device on Electronic
Cigarette User's Plasma Nicotine Concentration, Heart Rate, and Subjective
Effects Under Directed and Ad Libitum Use Conditions.
AB - Introduction: Electronic cigarettes e-cigarettes aerosolize a liquid solution
often containing nicotine. e-cigarette nicotine delivery may be influenced by
user puffing behaviors ("puff topography"). E-cigarette puff topography can be
recorded using mouthpiece-based computerized systems. The present study sought to
examine the extent to which these systems influence e-cigarette nicotine delivery
and other e-cigarette associated acute effects under ad libitum use conditions.
Methods: Plasma nicotine concentration, heart rate, and subjective effects were
assessed in 29 experienced e-cigarette users using their preferred e-cigarette
battery and liquid (>=12mg/mL nicotine) in two sessions differing only by the
presence of a mouthpiece-based device. In both sessions, participants completed a
directed e-cigarette use bout (10 puffs, 30-s interpuff interval) and a 90-min ad
libitum bout. Puff topography was recorded in the session with the topography
mouthpiece. Results: Plasma nicotine, heart rate, and subjective effects, aside
from "Did the e-cigarette Taste Good?" were independent of topography measurement
(higher mean taste ratings were observed in the no topography condition). Mean
(SEM) plasma nicotine concentration following the ad libitum bout was 34.3ng/mL
(4.9) in the no topography condition and 35.7ng/mL (4.3) in the topography
condition. Longer puff durations, longer interpuff intervals, and larger puff
volumes were observed in the ad libitum relative to the directed bout.
Conclusions: E-cigarette use significantly increased plasma nicotine
concentration and heart rate while suppressing abstinence symptoms. These effects
did not differ when a topography mouthpiece was present. Future studies using ad
libitum e-cigarette use bouts would facilitate understanding of e-cigarette
toxicant yield. Implications: No prior study has examined whether mouthpiece
based topography recording devices influence e-cigarette associated nicotine
delivery, heart rate, or subjective effects under ad libitum conditions or
assessed ad libitum puff topography in experienced individuals using their
preferred e-cigarette battery and liquid with a mouthpiece-based computerized
device. E-cigarette use significantly increased plasma nicotine concentration and
heart rate while suppressing abstinence symptoms. These effects did not differ
when a topography mouthpiece was present. Ad libitum puff topography differed
from puff topography recorded during directed puffing. These findings suggest
that future studies using ad libitum use bouts would facilitate better
understanding of e-cigarette toxicant yield.
PMID- 27613915
TI - Genotype * Environment Interaction in Smoking Behaviors: A Systematic Review.
AB - Introduction: There has been rapid growth in research exploring gene-environment
interaction (G*E) contributing to smoking behaviors. Yet, no systematic review
exists to date. Methods: This article aims to review evidence on the contribution
of G*E to the risk of smoking. Through a search of electronic databases (ie,
Google Scholar, PubMed, ScienceDirect, and Elsevier) up until May 2014, 16
studies of G*E focused on smoking behaviors were identified. These studies were
compared in terms of: research design and sample studied, measure of smoking
behavior and environments used, genes explored, and G*E in relation to these
factors. Results: Thirteen of 16 studies (81.2%) found at least one significant
G*E association. Wide variation in analytic methods was found across studies,
especially with respect to the phenotypes of interest, environmental measures
used, and tests conducted to estimate G*E. Heterogeneity across studies made it
difficult to compare findings and evaluate the strength of evidence for G*E.
Conclusions: G*E research on smoking contains studies that are methodologically
different, making it difficult to assess the current state of the evidence. To
decrease heterogeneity, we offer recommendations related to: (1) choice of
measurement for environmental variables, (2) testing and reporting of main and
interaction effects, (3) treatment of covariates, (4) reporting gene-environment
correlation, and (5) conducting sensitivity analyses and checking for scaling
artifacts. Continued study is needed to identify mechanisms by which genes and
environmental factors combine to influence smoking behaviors. Implications: No
comprehensive review of G*E studies of smoking behavior has previously been
published. The present article seeks to fill this gap by providing a
comprehensive review of: how G*E has been defined, how twin and molecular genetic
methodologies have been used to test for G*E, and which genes and environmental
factors are associated with smoking behaviors. Variations in methodological
approaches make it difficult to interpret and summarize findings, so
recommendations for future research are provided as a means to more easily
compare and replicate findings across studies.
PMID- 27613916
TI - Adolescents' Perceptions of an On-cigarette Health Warning.
AB - Introduction: In most countries, health warnings have been on cigarette packs for
decades. We explored adolescents' perceptions of a health warning on cigarettes.
Methods: Data come from the 2014 wave of a cross-sectional in-home survey with 11
to 16-year olds (N = 1205) from across the UK, with participants recruited from
the general population using random location quota sampling. Participants were
shown an image of a standard cigarette which displayed the warning "Smoking
kills" and asked whether they thought this would (not) put people off starting to
smoke, (not) make people want to give up smoking, and whether all cigarettes
should (not) have health warnings on them. Results: Most (71%) thought that an on
cigarette warning would put people off starting, although this decreased with
age. Never smokers were more likely than current smokers to think that it would
put people off starting. Approximately half (53%) thought that an on-cigarette
warning would make people want to give up smoking, with this higher for never
smokers and experimenters/past smokers than for current smokers. Most (85%)
supported a warning on all cigarettes. There was support among each smoking
group, although this was higher for never smokers and experimenters/past smokers
than for current smokers, and higher for those indicating that most of their
close friends do not smoke than for those indicating that most of their close
friends do smoke. Conclusions: The perception among adolescents that an on
cigarette warning could deter smoking, and the high support for a warning on all
cigarettes, warrants further research. Implications: Research on dissuasive
cigarettes is at a nascent stage. This is the first study to explore how
adolescents perceive a health warning ("Smoking kills") on cigarettes. Almost
three quarters of participants indicated that on-cigarette health warnings would
deter people from starting to smoke, and 85% supported the inclusion of a warning
on all cigarettes. While further research is clearly needed, these findings
suggest that the inclusion of health warnings on cigarettes is considered
appropriate by young people and may have a dissuasive effect.
PMID- 27613917
TI - Defining Tobacco Regulatory Science Competencies.
AB - INTRODUCTION: In 2013, the National Institutes of Health and the Food and Drug
Administration funded a network of 14 Tobacco Centers of Regulatory Science
(TCORS) with a mission that included research and training. A cross-TCORS Panel
was established to define tobacco regulatory science (TRS) competencies to help
harmonize and guide their emerging educational programs. The purpose of this
paper is to describe the Panel's work to develop core TRS domains and
competencies. METHODS: The Panel developed the list of domains and competencies
using a semistructured Delphi method divided into four phases occurring between
November 2013 and August 2015. RESULTS: The final proposed list included a total
of 51 competencies across six core domains and 28 competencies across five
specialized domains. CONCLUSIONS: There is a need for continued discussion to
establish the utility of the proposed set of competencies for emerging TRS
curricula and to identify the best strategies for incorporating these
competencies into TRS training programs. Given the field's broad
multidisciplinary nature, further experience is needed to refine the core domains
that should be covered in TRS training programs versus knowledge obtained in more
specialized programs. IMPLICATIONS: Regulatory science to inform the regulation
of tobacco products is an emerging field. The paper provides an initial list of
core and specialized domains and competencies to be used in developing curricula
for new and emerging training programs aimed at preparing a new cohort of
scientists to conduct critical TRS research.
PMID- 27613919
TI - Knowledge and Beliefs About E-Cigarettes in Straight-to-Work Young Adults.
AB - INTRODUCTION: Young adults are a growing segment of electronic cigarette (e
cigarette) users. Young adults who go straight to work (STW) from high school
make up a large portion of the young adult population, yet research to date has
focused on college-educated young adults. This study explored STW young adult
beliefs and knowledge about e-cigarettes. METHODS: Semistructured individual
interviews were used to elicit in-depth information from STW young adults ages 19
31 from a state in the southwest United States. Thirty interviews were conducted
focusing on beliefs about e-cigarettes, current knowledge, and information
seeking practices. Interviews were recorded, transcribed, and analyzed using
NVivo. RESULTS: Nine themes were identified falling into three categories: (1)
beliefs about e-cigarettes, (2) knowledge about e-cigarettes, and (3) personal
rules about e-cigarettes. STW young adults held positive beliefs about the health
and safety of e-cigarettes for themselves, others, and the environment. They
reported their social networks and the Internet as reliable sources of
information about e-cigarettes, but they reported parents as the best source for
advice. Participants had rules about e-cigarettes that contradicted some of their
beliefs such as using e-cigarettes around children indicating that their beliefs
were not as strongly held as they initially reported. CONCLUSIONS: Industry
marketing and contradictory information may contribute to STW young adult
knowledge and beliefs about e-cigarettes. Lack of credible public health
information may also contribute to this issue. Ensuring that what is known about
the benefits and harms of e-cigarettes is conveyed through multichannel
communication and continued monitoring of marketing practices of the e-cigarette
industry in light of the soon to be implemented regulations should be top
priorities for public health. IMPLICATIONS: Beliefs and knowledge of STW young
adults have not been explored even though they are heavily targeted by the e
cigarette industry. This group holds strong positive beliefs about the health and
safety of e-cigarettes, despite having little credible knowledge about them. This
study indicates a need for efforts focused on educating STW young adults on the
potential risks and benefits of e-cigarettes and the communication of credible
information or at minimum the acknowledgment of the uncertainty regarding the
long-term health effects of e-cigarettes. It also indicates a need for continued
monitoring and advocacy related to marketing practices of the e-cigarette
industry.
PMID- 27613918
TI - Share2Quit: Online Social Network Peer Marketing of Tobacco Cessation Systems.
AB - Introduction: Although technology-assisted tobacco interventions (TATIs) are
effective, they are underused due to recruitment challenges. We tested whether we
could successfully recruit smokers to a TATI using peer marketing through a
social network (Facebook). Methods: We recruited smokers on Facebook using online
advertisements. These recruited smokers (seeds) and subsequent waves of smokers
(peer recruits) were provided the Share2Quit peer recruitment Facebook app and
other tools. Smokers were incentivized for up to seven successful peer
recruitments and had 30 days to recruit from date of registration. Successful
peer recruitment was defined as a peer recruited smoker completing the
registration on the TATI following a referral. Our primary questions were (1)
whether smokers would recruit other smokers and (2) whether peer recruitment
would extend the reach of the intervention to harder-to-reach groups, including
those not ready to quit and minority smokers. Results: Overall, 759 smokers were
recruited (seeds: 190; peer recruits: 569). Fifteen percent (n = 117) of smokers
successfully recruited their peers (seeds: 24.7%; peer recruits: 7.7%) leading to
four recruitment waves. Compared to seeds, peer recruits were less likely to be
ready to quit (peer recruits 74.2% vs. seeds 95.1%), more likely to be male
(67.1% vs. 32.9%), and more likely to be African American (23.8% vs. 10.8%) (p <
.01 for all comparisons). Conclusions: Peer marketing quadrupled our engaged
smokers and enriched the sample with not-ready-to-quit and African American
smokers. Peer recruitment is promising, and our study uncovered several important
challenges for future research. Implications: This study demonstrates the
successful recruitment of smokers to a TATI using a Facebook-based peer marketing
strategy. Smokers on Facebook were willing and able to recruit other smokers to a
TATI, yielding a large and diverse population of smokers.
PMID- 27613920
TI - Association of Exercise Training with Tobacco Smoking Prevents Fibrosis but has
Adverse Impact on Myocardial Mechanics.
AB - INTRODUCTION: There was no data for cardiac repercussion of exercise training
associated with tobacco smoking. This issue is interesting because some smoking
people can be enrolled in an exercise-training program. Thus, we evaluated
swimming training effects on the function and structural myocardial in rats
exposed to tobacco smoking. METHODS: Male Wistar rats were assigned to one of
four groups: C, untrained rats without exposure to tobacco smoking; E, exercised
rats without exposure to tobacco smoking; CS, untrained rats exposed to tobacco
smoking; ECS, exercised rats exposed to tobacco smoking. Rats swam five times a
week twice daily (60min per session) for 8 weeks. Before each bout exercise, rats
breathed smoke from 20 cigarettes for 60min. Twenty-four hours after the last day
of the protocol, papillary muscles were isolated for in vitro analysis of
myocardial mechanics. The myocardial mass and nuclear cardiomyocyte volume were
used as hypertrophy markers, and collagen content was determined by picrosirius
red staining. RESULTS: There was a well-pronounced myocardial hypertrophic effect
for two interventions. The exercise blunted myocardial collagen increases induced
by tobacco smoking. However, exercise and tobacco-smoking association was
deleterious to myocardial performance. Thereby, in vitro experiments with
papillary muscles contracting in isometric showed impairment myocardial
inotropism in exercised rats exposed to tobacco smoking. CONCLUSIONS: This work
presents novel findings on the role of exercise training on cardiac remodeling
induced by tobacco smoking. Although exercise has mitigated tissue fibrosis,
their association with tobacco smoking exacerbated hypertrophy and in vitro
myocardial dysfunction. IMPLICATIONS: This is first study to show that the
association of an aerobic exercise training with tobacco smoking intensifies the
phenotype of pathological cardiac hypertrophy. Therefore, the combination of
interventions resulted in exacerbated myocardial hypertrophy and contractility
dysfunction. These findings have significant clinical implication because some
smoking people can be enrolled in an exercise-training program.
PMID- 27613921
TI - Resting-State Functional Connectivity of the Basal Nucleus of Meynert in
Cigarette Smokers: Dependence Level and Gender Differences.
AB - Introduction: Numerous studies have characterized impaired cerebral functioning
in nicotine-addicted individuals. Whereas nicotine interacts with multiple
neurotransmitters in cortical and subcortical circuits, it directly targets the
cholinergic system, sourced primarily from the basal nucleus of Meynert (BNM).
However, no studies have examined how this cholinergic system is influenced by
cigarette smoking. Here, we addressed this gap of research. Methods: Using a
dataset from the Functional Connectome Projects, we investigated this issue by
contrasting seed-based BNM connectivity of 40 current smokers and 170 age- and
gender-matched nonsmokers. We followed our data analytic routines in recent work
and examined differences between smokers and nonsmokers in men and women combined
as well as separately. Results: Compared to nonsmokers, female but not male
smokers demonstrated greater positive BNM connectivity to the supplementary motor
area, bilateral anterior insula, and right superior temporal/supramarginal gyri
as well as greater negative connectivity to the posterior cingulate cortex and
precuneus. Further, BNM connectivity to the supplementary motor area is
negatively correlated to the Fagerstrom Test for Nicotine Dependence score in
male but not female smokers. Conclusions: Along with a previous report of
upregulated nicotinic acetylcholine receptor in male but not female smokers,
these new findings highlight functional changes of the cholinergic systems in
cigarette smokers. The results suggest sex-specific differences in cholinergic
dysregulation and a need for multiple imaging modalities to capture the neural
markers of nicotine addiction. Implications: Nicotine influences cognition via
cholinergic projections of the basal forebrain to the cerebral cortex. This study
examined changes in resting-state whole-brain functional connectivity of the BNM
in cigarette smokers. The new findings elucidate for the first time sex
differences in BNM-cerebral connectivity in cigarette smoking.
PMID- 27613922
TI - The Impact of Tobacco Control Policies on Smoking Among Socioeconomic Groups in
Nine European Countries, 1990-2007.
AB - Background: It is uncertain whether tobacco control policies have contributed to
a narrowing or widening of socioeconomic inequalities in smoking in European
countries during the past two decades. This paper aims to investigate the impact
of price and non-price related population-wide tobacco control policies on
smoking by socioeconomic group in nine European countries between 1990 and 2007.
Methods: Individual-level education, occupation and smoking status were obtained
from nationally representative surveys. Country-level price-related tobacco
control policies were measured by the relative price of cheapest cigarettes and
of cigarettes in the most popular price category. Country-level non-price
policies were measured by a summary score covering four policy domains: smoking
bans or restrictions in public places and workplaces, bans on advertising and
promotion, health warning labels, and cessation services. The associations
between policies and smoking were explored using logistic regressions, stratified
by education and occupation, and adjusted for age, Gross Domestic Product, period
and country fixed effects. Results: The price of popular cigarettes and non-price
policies were negatively associated with smoking among men. The price of the
cheapest cigarettes was negatively associated with smoking among women. While
these favorable effects were generally in the same direction for all
socioeconomic groups, they were larger and statistically significant in lower
socioeconomic groups only. Conclusions: Tobacco control policies as implemented
in nine European countries, have probably helped to reduce the prevalence of
smoking in the total population, particularly in lower socioeconomic groups.
Widening inequalities in smoking may be explained by other factors. Policies with
larger effects on lower socioeconomic groups are needed to reverse this trend.
Implications: Socioeconomic inequalities in smoking widened between the 1990s and
the 2000s in Europe. During the same period, there were intensified tobacco
control policies in many European countries. It is uncertain whether tobacco
control policies have contributed to a narrowing or widening of socioeconomic
inequalities in smoking in European countries. This study shows that tobacco
control policies as implemented in the available European countries have helped
to reduce the prevalence of smoking in the total population, particularly in
lower socioeconomic groups. Widening inequalities in smoking may be explained by
other factors.
PMID- 27613923
TI - Implications of Personal Genomic Testing for Health Behaviors: The Case of
Smoking.
AB - INTRODUCTION: Direct-to-consumer personal genomic testing has the potential to
influence health behaviors, including smoking. Critics of this testing highlight
limited evidence to support positive behavioral benefits and caution that genomic
results may provide false reassurance, leading to unhealthy behaviors. This study
investigates interest in genetic risks of smoking-related diseases and changes in
smoking behaviors among genomic testing consumers. METHODS: From 2012 to 2013, a
longitudinal series of web surveys was conducted. A total of 1464 customers of
23andMe and Pathway Genomics completed a survey prior to viewing genomic test
results, of which 1002 participants provided data on smoking behaviors 6 months
after receiving results. RESULTS: At baseline, 64% of participants were never
smokers, 29% were former smokers, and 7% were current smokers. Most baseline
current smokers were very interested in genetic risk results for lung cancer
(65%) and heart disease (72%). For lung cancer, this interest was significantly
greater than former (50% very interested) and never smokers (37% very interested)
(p < .0001). Even though participants were interested in smoking-related disease
genetic risks, 96% reported the same smoking status at baseline and 6-month
follow-up. Importantly, only 1% (n = 13/916) of former and never smokers became
current smokers at 6 months and 22% (n = 14/64) of current smokers reported
quitting. CONCLUSIONS: Overall, smokers show a high level of interest in genetic
risks of smoking-related illnesses. The experience of receiving direct-to
consumer genomic health risks does not appear to have obvious harms related to
smoking behaviors, with some potential benefits. IMPLICATIONS: In the setting of
ongoing controversy surrounding direct-to-consumer genomic testing, this study
provides evidence that consumers are interested in genetic risk results of
smoking-related diseases. Receiving genomic testing results does not lead to
smoking initiation among never smokers or reinitiation among former smokers and
may be associated with a higher quit rate among current smokers at 6-month follow
up than the general population. These findings ease concerns that direct-to
consumer genomic testing could lead to false reassurance and unhealthy behaviors
related to smoking.
PMID- 27613924
TI - Young Adult Perceptions of the British American Tobacco New Zealand
Agree/Disagree Plain Packaging Counter-Campaign.
AB - Introduction: In 2012, British American Tobacco New Zealand (BATNZ) launched a
mass media campaign branded "Agree/ Disagree" as a response to the New Zealand
government's plans to introduce plain packaging. We examined young adult's views
about the campaign to assist tobacco control policymakers in planning future
interventions. Methods: Interviews with young adults living in the Auckland area
were conducted. Interviews covered existing knowledge about plain packaging of
tobacco, knowledge about the tobacco industry, and perceptions of specific
advertisements included in the campaign. Interview data were analyzed to
determine the dominant views about the campaign. Results: Perspectives from 12
interviews reflect the dominant discourse in New Zealand on the benefits of
serving economic progress and international trade. Pervasive views about the
campaigns reflected perceptions of the risk to the New Zealand image, trade, and
economy. Similarly, participants expressed concern about the potential for plain
packaging to creep toward other products, such as alcohol. Perceptions of the
tobacco industry were mixed but reflect a tolerant view of the ethics of business
if viewed to be beneficial to the economy. Discussion: Participants were broadly
accepting of the campaign messages. We identified a tendency toward quasi
libertarian leanings when discussing economics and trade, commercial versus
personal responsibility, and the value of freedom (commercial and social). These
perspectives were often held simultaneously with conflicting socially responsive
values and references to the hegemonic position of "big business." Conclusion:
This study affirms the importance of closely monitoring public opinion about
tobacco control and of broadening denormalization strategies to reflect the
critical role the tobacco industry plays in prolonging the tobacco epidemic.
Implications: To date there is little evidence on the perceptions young adults
hold toward to the tobacco industry and their arguments regarding the
introduction of plain packaged cigarettes. Our findings indicate that some young
people are attuned to the social discourse regarding the importance of economics,
individuality, choice, and freedom as expressed by the tobacco industry. Tobacco
control initiatives could challenge core values such as fairness and justice as
related to corporate behaviors to retain public support, particularly among young
people.
PMID- 27613926
TI - Structured Smoking Cessation Training for Medical Students: A Prospective Study.
AB - INTRODUCTION: Physician adherence to guideline recommendations regarding the
provision of counseling and support for smokers willing to quit is low. A lack of
training during undergraduate medical education has been identified as a
potential cause. This prospective intervention study evaluated a novel teaching
module for medical students. METHODS: As part of a 6-week cardiovascular course,
125 fourth-year undergraduate medical students received a multimodal and
interactive teaching module on smoking cessation, including online learning
material, lectures, seminars, and practical skills training. Short- and medium
term effects on knowledge, skills, attitudes, and self-reported practice were
measured using written examinations and an objective structured clinical
examination at the end of the module and 6 months later. Results were compared to
data obtained from a historical control cohort (n = 70) unexposed to the
intervention. RESULTS: At the 6-month follow-up, scores in the knowledge test
were significantly higher in the intervention than the control group (61.1% vs.
51.7%; p < .001). A similar pattern was observed in the objective structured
clinical examination (71.5% vs. 60.5%; p < .001). More students in the
intervention than control group agreed that smoking was a chronic disease (83.1%
vs. 68.1%; p = .045). The control group was more likely to report recording
smoking status (p = .018), but no group difference was detected regarding the
report of advising to quit (p = .154). CONCLUSIONS: A novel teaching module for
undergraduate medical students produced a sustained learning outcome in terms of
knowledge, skills, and attitudes but not self-reported practice. IMPLICATIONS:
Studies across the world have identified considerable knowledge gaps and deficits
in practical training with regard to smoking cessation counseling in
undergraduate medical students. This paper describes a teaching intervention
informed by current recommendations for the design of educational activities
aimed at enabling medical students to deliver adequate behavior change
counseling. The teaching module was tailored to the needs of a specific
healthcare system. Given its effectiveness as demonstrated in this prospective
study, a rollout of this intervention in medical schools might have the potential
to substantially improve medical students' knowledge, skills, and attitudes in
relation to smoking cessation counseling.
PMID- 27613925
TI - Transitions in Smokers' Social Networks After Quit Attempts: A Latent Transition
Analysis.
AB - INTRODUCTION: Smokers' social networks vary in size, composition, and amount of
exposure to smoking. The extent to which smokers' social networks change after a
quit attempt is unknown, as is the relation between quitting success and later
network changes. METHODS: Unique types of social networks for 691 smokers
enrolled in a smoking-cessation trial were identified based on network size, new
network members, members' smoking habits, within network smoking, smoking
buddies, and romantic partners' smoking. Latent transition analysis was used to
identify the network classes and to predict transitions in class membership
across 3 years from biochemically assessed smoking abstinence. RESULTS: Five
network classes were identified: Immersed (large network, extensive smoking
exposure including smoking buddies), Low Smoking Exposure (large network, minimal
smoking exposure), Smoking Partner (small network, smoking exposure primarily
from partner), Isolated (small network, minimal smoking exposure), and Distant
Smoking Exposure (small network, considerable nonpartner smoking exposure).
Abstinence at years 1 and 2 was associated with shifts in participants' social
networks to less contact with smokers and larger networks in years 2 and 3.
CONCLUSIONS: In the years following a smoking-cessation attempt, smokers' social
networks changed, and abstinence status predicted these changes. Networks defined
by high levels of exposure to smokers were especially associated with continued
smoking. Abstinence, however, predicted transitions to larger social networks
comprising less smoking exposure. These results support treatments that aim to
reduce exposure to smoking cues and smokers, including partners who smoke.
IMPLICATIONS: Prior research has shown that social network features predict the
likelihood of subsequent smoking cessation. The current research illustrates how
successful quitting predicts social network change over 3 years following a quit
attempt. Specifically, abstinence predicts transitions to networks that are
larger and afford less exposure to smokers. This suggests that quitting smoking
may expand a person's social milieu rather than narrow it. This effect, plus
reduced exposure to smokers, may help sustain abstinence.
PMID- 27613927
TI - The Association of Menthol Cigarette Use With Quit Attempts, Successful
Cessation, and Intention to Quit Across Racial/Ethnic Groups in the United
States.
AB - Introduction: Few studies have examined the relationship between menthol use and
smoking cessation across various racial/ethnic groups; the findings were mixed.
This study explored the association of menthol cigarette use with quit attempts,
smoking cessation, and intention-to-quit among US adults and by race/ethnicity.
Methods: Using the 2006/2007 and 2010/2011 Tobacco Use Supplements to the Current
Population Survey data, this study analyzed 54 448 recent active smokers, defined
as current smokers or former smokers who quit less than 12 months ago. Three
behaviors were examined: any quit attempts in the past 12 months, successful
cessation for >=3 months, and intention-to-quit smoking in the next 6 months. For
each cessation behavior, multiple logistic regression models were estimated
separately for the full-sample and stratified racial/ethnic subsamples. Results:
While 72.3% of African American recent active smokers typically smoked menthol
cigarettes, this proportion was 21.7%, 21.5%, and 28.0% for whites, Asians, and
Hispanics, respectively. African American menthol smokers had higher odds of quit
attempts compared to non-African American, non-menthol smokers (full-sample
analysis), as well as African American non-menthol smokers (subsample analysis).
Menthol use was not significantly associated with quit attempts in other
racial/ethnic subsamples. There was no significant difference in either
successful cessation or intention-to-quit between menthol and non-menthol
smokers. Conclusions: African American menthol smokers were more likely to
attempt to quit smoking than non-menthol smokers but these quit attempts did not
translate into successful cessation. This study revealed no association of
menthol use with quit attempts, successful cessation, and intention-to-quit among
other racial/ethnic groups. Implications: The findings suggested that African
American menthol smokers were more motivated to quit smoking; yet, the results
also indicated no significant differences in successful cessation between African
American menthol and non-menthol smokers. Interventions targeting menthol smokers
within the African American community may help bridge this gap. While more local
sales restrictions are beginning to occur (eg, Tobacco 21 efforts), additional
policies restricting price discounting as well as the regulation of access to and
the time, place, and/or manner of menthol tobacco advertising could also improve
cessation rates. Further evaluation is needed to determine the viability of these
policies.
PMID- 27613928
TI - Does Quitting Smoking Make a Difference Among Newly Diagnosed Head and Neck
Cancer Patients?
AB - INTRODUCTION: To determine if smoking after a cancer diagnosis makes a difference
in mortality among newly diagnosed head and neck cancer patients. METHODS:
Longitudinal data were collected from newly diagnosed head and neck cancer
patients with a median follow-up time of 1627 days (N = 590). Mortality was
censored at 8 years or September 1, 2011, whichever came first. Based on smoking
status, all patients were categorized into four groups: continuing smokers,
quitters, former smokers, or never-smokers. A broad range of covariates were
included in the analyses. Kaplan-Meier curves, bivariate and multivariate Cox
proportional hazards models were constructed. RESULTS: Eight-year overall
mortality and cancer-specific mortality were 40.5% (239/590) and 25.4% (150/590),
respectively. Smoking status after a cancer diagnosis predicted overall mortality
and cancer-specific mortality. Compared to never-smokers, continuing smokers had
the highest hazard ratio (HR) of dying from all causes (HR = 2.71, 95% confidence
interval [CI] = 1.48-4.98). Those who smoked at diagnosis, but quit and did not
relapse-quitters-had an improved hazard ratio of dying (HR = 2.38, 95% CI = 1.29
4.36) and former smokers at diagnosis with no relapse after diagnosis-former
smokers-had the lowest hazard ratio of dying from all causes (HR = 1.68, 95% CI =
1.12-2.56). Similarly, quitters had a slightly higher hazard ratio of dying from
cancer-specific reasons (HR = 2.38, 95% CI = 1.13-5.01) than never-smokers, which
was similar to current smokers (HR = 2.07, 95% CI = 0.96-4.47), followed by
former smokers (HR = 1.70, 95% CI = 1.00-2.89). CONCLUSIONS: Compared to never
smokers, continuing smokers have the highest HR of overall mortality followed by
quitters and former smokers, which indicates that smoking cessation, even after a
cancer diagnosis, may improve overall mortality among newly diagnosed head and
neck cancer patients. Health care providers should consider incorporating smoking
cessation interventions into standard cancer treatment to improve survival among
this population. IMPLICATIONS: Using prospective observational longitudinal data
from 590 head and neck cancer patients, this study showed that continuing smokers
have the highest overall mortality relative to never-smokers, which indicates
that smoking cessation, even after a cancer diagnosis, may have beneficial
effects on long-term overall mortality. Health care providers should consider
incorporating smoking cessation interventions into standard cancer treatment to
improve survival among this population.
PMID- 27613929
TI - Socioeconomic Disadvantage and Other Risk Factors for Using Higher-Nicotine/Tar
Yield (Regular Full-Flavor) Cigarettes.
AB - Introduction: Use of machine-estimated higher nicotine/tar yield (regular full
flavor) cigarettes is associated with increased risk of nicotine dependence. The
present study examined risk factors for using full-flavor versus other cigarette
types, including socioeconomic disadvantage and other risk factors for tobacco
use or tobacco-related adverse health impacts. Associations between use of full
flavor cigarettes and risk of nicotine dependence were also examined. Methods:
Data were obtained from nationally representative samples of adult cigarette
smokers from the US National Survey on Drug Use and Health. Logistic regression
and classification and regression tree modeling were used to examine associations
between use of full-flavor cigarettes and educational attainment, poverty,
race/ethnicity, age, sex, mental illness, alcohol abuse/dependence, and illicit
drug abuse/dependence. Logistic regression was used to examine risk for nicotine
dependence. Results: Each of these risk factors except alcohol abuse/dependence
independently predicted increased odds of using full-flavor cigarettes (p <
.001), with lower educational attainment the strongest predictor, followed by
poverty, male sex, younger age, minority race/ethnicity, mental illness, and drug
abuse/dependence, respectively. Use of full-flavor cigarettes was associated with
increased odds of nicotine dependence within each of these risk factor groupings
(p < .01). Cart modeling identified how prevalence of full-flavor cigarette use
can vary from a low of 25% to a high of 66% corresponding to differing
combinations of these independent risk factors. Conclusions: Use of full-flavor
cigarettes is overrepresented in socioeconomically disadvantaged and other
vulnerable populations, and associated with increased risk of nicotine
dependence. Greater regulation of this cigarette type may be warranted.
Implications: Greater regulation of commercially available Regular Full-Flavor
Cigarettes may be warranted. Use of this type of cigarette is overrepresented in
socioeconomically disadvantaged and other vulnerable populations and associated
with increased risk for nicotine dependence.
PMID- 27613931
TI - Online Information About Harmful Tobacco Constituents: A Content Analysis.
AB - Introduction: Tobacco products and smoke contain more than 7000 chemicals (ie,
constituents). Research shows that consumers have poor understanding of tobacco
constituents and find communication about them to be confusing. The current
content analysis describes how information is communicated about tobacco
constituents online in terms of source, target audience, and message. Methods: A
search was conducted in September 2015 using tobacco constituent and tobacco
terms and identified 226 relevant Web sites for coding. Web sites were coded for
type, target audience, reading level, constituent information, type of tobacco
product, health effects, and emotional valence by two coders who independently
coded half of the sample. There was a 20% overlap to assess interrater
reliability, which was high (kappa = .83, p < .001). Results: The mean reading
grade level of information online was 8.2 (SD = 2.8) with 81.7% of Web sites
above the sixth grade reading level. Nearly all Web sites presented information
in a qualitative narrative format (93%) and almost half (48.2%) presented
information in a quantitative format. Nicotine (59.3%) and nitrosamines (28.8%)
were the mostly frequently mentioned tobacco constituents. Cancer was the most
frequently mentioned health effect (51.3%). Nearly a quarter (23%) of the Web
sites did not explicitly state that tobacco constituents or tobacco products are
associated with health effects. Conclusion: Large gaps exist in online
information about tobacco constituents including incomplete information about
tobacco constituent-related health effects and limited information about tobacco
products other than cigarettes and smokeless tobacco. This study highlights
opportunities to improve the content and presentation of information related to
tobacco constituents. Implications: The US Food and Drug Administration (FDA) is
required to publicly display a list of tobacco constituents in tobacco products
and tobacco smoke by brand. However, little is known about tobacco constituent
information available to the public. This is the first systematic content
analysis of online information about tobacco constituents. The analysis reveals
that although information about tobacco constituents is available online, large
information gaps exist, including incomplete information about tobacco
constituent-related health effects. This study highlights opportunities to
improve the content and presentation of public information related to tobacco
constituents.
PMID- 27613930
TI - Changes in Smoking Intensity Over Time by Birth Cohort and by Latino National
Background, 1997-2014.
AB - INTRODUCTION: The purpose of the study was to describe changes in smoking
intensity among US Latinos and non-Latinos from 1997 to 2014. METHODS: National
Health Interview Survey data between 1997 and 2014 were used to determine the
number of cigarettes smoked per day (CPD) among Latino and non-Latino adults who
had smoked at least 100 cigarettes in their lifetime and were currently smoking
every day or some days (ie, current smokers). RESULTS: CPD declined steadily
throughout the observation period and were consistently lower for Latino than for
non-Latino smokers. However, decreases were not equal across birth cohorts,
genders, or among Latino national background groups. CPD declined most among
Mexican men and least among younger generations, Cuban women, and acculturated
Latina women. Additionally, declines in smoking intensity seemed to slow over
time among low CPD consumers. CONCLUSIONS: Although smoking intensity has
decreased substantially since the late 1990s, CPD data suggest that declines are
slowing among younger generations and certain Latina women. Effective tobacco
control strategies should be developed to discourage even very light and nondaily
smoking. IMPLICATIONS: Few studies have been conducted on how smoking intensity
has changed since the late 1990s. Between 2004 and 2011, when the decline in
smoking prevalence slowed, it is unknown how smoking intensity (ie, CPD) changed
by age. Additionally, no research has assessed differences and changes in smoking
intensity over time among Latinos. From this study we learned that smoking
intensity declined significantly since the late 1990s, but this decline slowed
among younger generations of smokers and certain Latina women. Findings suggest
that future patterns of smoking intensity may only marginally decline in the near
future.
PMID- 27613932
TI - Problematic Assessment of the Impact of Vaporized Nicotine Product Initiation in
the United States.
PMID- 27613933
TI - Social Acceptance of Smoking Restrictions During 10 Years of Policy
Implementation, Reversal, and Reenactment in the Netherlands: Findings From a
National Population Survey.
AB - INTRODUCTION: Little is known about the extent to which smoking restrictions are
socially accepted in a country such as the Netherlands where smoking restrictions
have been implemented and reversed several times. The current study assessed
trends as well as factors associated with two indicators of social acceptance of
smoking restrictions in the Netherlands: acceptance of smoking in public places
and implementation of home smoking bans. METHODS: We used data from the Dutch
Continuous Survey of Smoking Habits (DCSSH) between 2005 and 2014 (n = 182826).
The DCSSH is a national population survey with a cross-sectional design in which
respondents aged 15 years and older are surveyed weekly. RESULTS: Acceptance of
smoking in public places decreased for six out of eight included venues, with the
largest decrease for smoking in restaurants. The decrease in acceptance was
larger among younger respondents and smokers. Smoking on terraces was an
exception: decrease in acceptance there was larger among older respondents and ex
smokers. Implementation of home smoking bans increased over time. Having
implemented a home smoking ban was associated with being male, being younger,
having a high socioeconomic status, and being ex- or never smoker. CONCLUSIONS:
Social acceptance of smoking restrictions has increased in the Netherlands,
despite a suboptimal implementation process of smoking restrictions. However,
there is still potential for improvement as acceptance of smoking is still quite
high for some public venues like bars. It is important to strengthen smoking
restrictions in order to further denormalize smoking in the Netherlands.
IMPLICATIONS: We examined the extent to which smoking restrictions are socially
accepted in the Netherlands where smoking restrictions have been implemented and
reversed several times. Acceptance of smoking in public places decreased and
implementation of home smoking bans increased between 2005 and 2014. Social
acceptance of smoking restrictions increased in the Netherlands despite a
suboptimal implementation process of smoking restrictions. However, acceptance of
smoking in bars remains relatively high.
PMID- 27613935
TI - Smokers' Perspectives on Texting for Tobacco Dependence Treatment: A Qualitative
Analysis.
AB - Background: Numerous evidence-based pharmacologic and behavioral approaches exist
for the treatment of tobacco dependence. Short-message service texting is a newer
modality which shows promise, but smokers' perspectives on texting have not been
widely explored. Objective: To use a qualitative research approach to elicit from
a sub-sample of participants in a pilot clinical trial their perspectives
concerning the feasibility, acceptability, and personal relevance of a publicly
available texting program for smoking cessation. Methods: Adult smokers enrolled
in the intervention arm in a randomized trial of tobacco treatment were
interviewed by telephone. Consenting subjects engaged in a 15-30min semi
structured interview with a trained research assistant, discussing their
experience with and attitudes about the texting program and how it affected their
tobacco use. Interviews were audio-recorded, transcribed verbatim, and analyzed
thematically. Descriptive statistics were calculated for the 16 Likert-formatted
items. Results: Of 30 subjects in the intervention arm, 25 (83%) agreed to
participate in the qualitative interviews. In general subjects found the program
helpful. Common themes were that the texts served as a form of social support,
provided useful strategies to reduce tobacco use, validated subjects' attempts to
quit, and offered welcome distractions from cravings. Subjects were satisfied
with the frequency, timing, and number of texts, although some improvements were
suggested. Conclusions: Texting was perceived as feasible, acceptable, and
helpful in smokers' attempts to abstain from tobacco. Implications: The major
themes identified included the program being a valued source of external support
that provided useful strategies to reduce tobacco use. Subjects were satisfied
with the frequency, timing, and number of texts. Texting was perceived as
feasible, acceptable, and helpful in smokers' attempts to abstain from tobacco.
Suggestions to improve the program primarily concerned increasing customizable
options and using simple, declarative sentences.
PMID- 27613934
TI - Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo
Controlled Randomized Trial.
AB - INTRODUCTION: Pregnancy is a strong motivator to quit smoking, yet postpartum
relapse rates are high. Growing evidence suggests a role of sex hormones in drug
abuse behavior and given the precipitous drop in sex hormones at delivery, they
may play a role in postpartum relapse. This pilot study evaluates the feasibility
and potential role of exogenous progesterone in postpartum smoking relapse.
METHODS: This 12-week double-blind placebo-controlled randomized pilot trial
randomized 46 abstinent postpartum women to active progesterone (PRO; 200mg twice
a day) versus placebo (PBO) for 4 weeks. Participants were followed for relapse
for 12 weeks. Main study outcomes include abstinence (point prevalence),
feasibility (compliance per number of clinic visits attended, pill counts and
Electronic Data Capture [EDC] completed) and self-reported acceptability. Safety
was also measured by depressive symptom scores, adverse events, and
breastfeeding. RESULTS: Overall retention rate was 87% at week 12. At week 4,
abstinence rates were 75% in the PRO group and 68.2% in the PBO group (p = .75).
Medication adherence was 68% and clinic visit attendance was 80%, with no
differences by randomization. Depressive symptom scores, adverse events, and
breastfeeding did not vary by randomization. CONCLUSIONS: Although the study was
not powered to evaluate abstinence rates, we did observe a higher prevalence of
abstinence at week 4 in the PRO group. Further, exogenous progesterone was well
tolerated and did not adversely affect depressive symptoms or breastfeeding.
Thus, the results of this pilot study indicate further investigation into
progesterone as a postpartum relapse prevention strategy is warranted.
IMPLICATIONS: This innovative pilot trial determined the feasibility of
delivering exogenous progesterone as a potential prevention of postpartum smoking
relapse. We observed high retention and moderate adherence rates, as well as high
acceptability among participants. Further, though not statistically significant,
more women in the treatment group remained abstinent from smoking during follow
up. This project adds to the growing body of literature on the role of sex
hormones in smoking relapse and also provides support for a fully powered
clinical trial.
PMID- 27613936
TI - High Prevalence of Smoking in the Roma Population Seems to Have No Genetic
Background.
AB - INTRODUCTION: The prevalence of smoking in Romani of both genders is
significantly higher than in the general population. Our aim was to determine
whether a genetic susceptibility contributes to the high prevalence of smoking
among Roma in a study based on data collected from cross-sectional surveys.
METHODS: Twenty single nucleotide polymorphisms known to be closely related to
smoking behavior were investigated in DNA samples of Hungarian Roma (N = 1273)
and general (N = 2388) populations. Differences in genotype and allele
distribution were investigated. Genetic risk scores (GRSs) were generated to
estimate the joint effect of single nucleotide polymorphisms in genes COMT,
CHRNA3/4/5, CYP2A6, CTNNA3, DRD2, MAOA, KCNJ6, AGPHD1, ANKK1, TRPC7, GABRA4, and
NRXN1. The distribution of scores in study populations was compared. Age, gender,
and body mass index were considered as confounding factors. RESULTS: Difference
in allele frequencies between the study populations remained significant for 16
polymorphisms after multiple test correction (p < .003). Unexpectedly, the
susceptible alleles were more common in the general population, although the
protective alleles were more prevalent among Roma. The distribution of unweighted
GRS in Roma population was left shifted compared to general population (p <
.001). Furthermore, the median weighted GRS was lower among the subjects of Roma
population compared to the subjects of general population (p < .001) even after
adjustment for confounding factors. CONCLUSIONS: The harmful smoking behavior of
the Roma population could not be accounted for by genetic susceptibility;
therefore, interventions aimed at smoking prevention and cessation should focus
on cultural and environmental factors. IMPLICATIONS: This is the first study
designed to determine whether genetic background exists behind the harmful
behavior of the smoking of the Roma population. Although the frequencies of
susceptible and protective alleles strongly differ between the Hungarian Roma and
general populations, it is shown that calculated GRSs being significantly higher
in the general population, which do not support the hypothesis on the genetic
susceptibility of the Roma population. Interventions aimed at smoking cessation
in the Roma population should preferentially target cultural and environmental
factors.
PMID- 27613937
TI - Worsening Dietary and Physical Activity Behaviors Do Not Readily Explain Why
Smokers Gain Weight After Cessation: A Cohort Study in Young Adults.
AB - Introduction: The relationship between smoking cessation and weight gain is well
established but the underlying mechanisms remain poorly understood. We aimed to
determine whether postcessation weight gain was mediated by changing health
behaviors. Methods: A total of 281 smokers self-reported their demographic,
smoking, and lifestyle characteristics in 2004-2006 (aged 26-36) and 2009-2011
(aged 31-41). Behaviors considered as potential mediators of weight gain were
changes in consumption of breakfast, discretionary foods (servings/d), fruit and
vegetables (servings/d), alcohol (g/d), takeaway food (times/wk), Diet Guideline
Index score, leisure time physical activity (PA, min/wk), total PA (min/wk), time
spent sitting (min/d), and TV viewing (h/d). Results: In total, 124 smokers quit
smoking during 5 years follow-up. After adjustment for age, sex, baseline body
mass index, education, and follow-up length, smoking cessation was associated
with average excess weight gain of 2.09kg (95% CI = 0.35-3.83). Compared with
continuing smokers, quitters reported a higher Diet Guideline Index score and
less consumption of alcohol at baseline and follow-up (all p < .05). In addition,
there was a tendency towards healthier dietary and PA behaviors over 5 years
among quitters than continuing smokers except for time spent sitting, although
these differences did not reach statistical significance. Adjustment for changes
in these behaviors made little difference to the magnitude of postcessation
weight gain (beta: 2.32kg, 95% CI = 0.54-4.10). Conclusions: The weight gain
associated with smoking cessation was not explained by worsening dietary and PA
behaviors. Future research is needed to elucidate the complex mechanisms and
particularly ways it may be prevented. Implications: Fear of weight gain often
discourages smokers from trying to quit but guidance on ways to most effectively
avoid weight gain is lacking. It is important to identify what causes
postcessation weight gain and the ways it may be prevented. The current study
explored the effects of several changing dietary and PA behaviors on the
relationship between smoking cessation and weight gain in 281 young Australian
smokers. We found that quitters tended to adopt healthier dietary and PA
behaviors than continuing smokers, so these behaviors did not readily explain the
postcessation weight gain. Further investigations of other potential mechanisms
are needed.
PMID- 27613938
TI - The Social Gradient in Tobacco Use Does Not Generalize to Low-Income Urban
Communities in India: Findings From a Census Survey.
AB - Introduction: The existence of a social gradient in tobacco use has been clearly
established in a number of countries with people with lower socioeconomic status
being more likely to use tobacco. It is not clear how far this gradient is
evident within severely deprived communities. This study assessed the association
between occupation as a marker of socioeconomic status and use of smoked and
smokeless tobacco within "slum" areas of Delhi, India. Methods: A census survey
of 11 888 households, comprising 30 655 adults from 28 low-income communities (14
government-authorized and 14 unauthorized settlements called "Jhuggi-Jhopri/JJ"
clusters) was conducted in 2012. The survey assessed age, sex, household size,
occupational group, and current tobacco use. Independent associations with
tobacco use were conducted using complex samples regression analysis, stratified
by gender. Results: A quarter of participants (24.3%, 95% confidence interval
[CI] 21.5-27.5) used any tobacco. Slightly more people used smoked (14.6%, 95% CI
12.9-16.3) than smokeless (12.6%, 95% CI 10.7-14.8) tobacco, with a small
minority being dual users (2.7%, 95% CI 2.1-3.5). Prevalence of any tobacco use
was highest in unskilled (45.13%, 95% CI 42.4-47.9) and skilled (46.2%, 95% CI
41.1-51.4) manual occupations and lower in nonmanual (30.3%, 95% CI 26.2-34.7)
occupations and those who were unemployed (29.0%, 95% CI 25.3-33.0). This was
confirmed in adjusted analysis in men but associations were more complex in
women. Conclusions: Use of smoked and smokeless tobacco in low-income urban
communities in India has a complex association with occupational status with both
nonmanual occupation and unemployment being associated with lower prevalence of
smoked and smokeless tobacco in men. Implications: Tobacco use in high-income
countries shows a strong inverse relationship with social grade, income, and
deprivation such that use is much more common among those who can least afford
it. This study is the first to look at this social gradient in the context of low
income communities in India, finding that both unemployment and nonmanual
occupation were associated with lower rates of tobacco use in men. The data
present a challenge to existing explanations of the social gradient, requiring
further consideration of the conditions under which affordability may work to
reduce health inequalities arising from tobacco use.
PMID- 27613939
TI - Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.
AB - Introduction: Under-dosing is a recognized problem with current nicotine
replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed.
To compare the nicotine uptake from the 6mg gum versus currently available NRT
products, two pharmacokinetic studies were performed. Methods: In one randomized
crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg
nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate
randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers
received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every
hour, and one 4mg lozenge every hour. In both studies, blood samples were
collected over 12 hours to determine single-dose and multiple-dose
pharmacokinetic variables. Results: In the single-dose study, the amount of
nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as
the resulting maximum concentration and area under the curve (5.9, 10.1, and
13.8ng/mL, and 17.1, 30.7, 46.2ng/mL * h, respectively) increased with dose. The
maximum concentration and area under the curve of the 6mg gum were 44% and 30%
greater, respectively, than those for 4mg lozenge. Upon hourly administration,
the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL)
was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum
(27.1ng/mL). Conclusions: Nicotine delivery via the 6mg gum results in higher
plasma nicotine concentrations after a single dose and at steady state than with
currently available oral NRT. Implications: Under-dosing is a recognized problem
with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our
studies show that upon single-dose and multiple-dose administration, the 6mg gum
releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg
gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of
nicotine substitution and/or lasts for a longer period of time than currently
available nicotine gums and lozenges.
PMID- 27613941
TI - Randomized Controlled Trial of Group-Based Culturally Specific Cognitive
Behavioral Therapy Among African American Smokers.
AB - Introduction: This study tested the efficacy of group-based culturally specific
cognitive behavioral therapy (CBT) for smoking cessation among low-income African
Americans. Methods: Participants (N = 342; 63.8% male; M = 49.5 years old; M
cigarettes per day = 18) were randomly assigned to eight sessions of group-based
culturally specific or standard CBT, plus 8 weeks of transdermal nicotine
patches. Biochemically verified 7-day point prevalence abstinence (ppa) was
assessed at the end-of-therapy (ie, CBT) (EOT), and 3-, 6-, and 12-month follow
ups. Primary outcomes were the longitudinal intervention effect over the 12-month
follow-up period, and 7-day ppa at the 6-month follow-up. Secondary outcomes
included 7-day ppa at the EOT and 12-month follow-up, and intervention ratings.
Generalized linear mixed modeling tested the longitudinal effect and logistic
regression tested effects at specific timepoints. Results: Generalized linear
mixed modeling demonstrated a longitudinal effect of intervention condition.
Specifically, 7-day ppa was two times (P = .02) greater following culturally
specific CBT versus standard CBT when tested across all timepoints. Analyses by
timepoint found no significant difference at 6 or 12 months, yet culturally
specific CBT was efficacious at the EOT (62.5% vs. 51.5% abstinence, P = .05) and
the 3-month follow-up (36.4% vs. 22.9% abstinence, P = .007). Finally,
intervention ratings in both conditions were high, with no significant
differences. Conclusions: Culturally specific CBT had a positive longitudinal
effect on smoking cessation compared to a standard approach; however, the effects
were driven by short-term successes. We recommend the use of group-based
culturally specific CBT in this population when possible, and future research on
methods to prevent long-term relapse. Implications: Culturally specific
interventions are one approach to address smoking-related health disparities;
however, evidence for their efficacy in African Americans is equivocal. Moreover,
the methodological limitations of the existing literature preclude an answer to
this fundamental question. We found a positive longitudinal effect of culturally
specific CBT versus standard CBT for smoking cessation across the follow-up
period. Analyses by assessment point revealed that the overall effect was driven
by early successes. Best practices for treating tobacco use in this population
should attend to ethnocultural factors, but when this is not possible, standard
CBT is an alternative approach for facilitating long-term abstinence.
PMID- 27613940
TI - Inter-relationships Linking Probability of Becoming a Case of Nicotine Dependence
With Frequency of Tobacco Cigarette Smoking.
AB - INTRODUCTION: Once smoking starts, some tobacco cigarette smokers (TCS) can make
very rapid transitions into tobacco dependence syndromes (TCD). With adjustment
for smoking frequency, we posit female excess risk for this rapid-onset TCD. In a
novel application of functional analysis for tobacco research, we estimate four
Hill function parameters and plot TCD risk against a gradient of smoking
frequency, as observed quite soon after smoking onset. METHODS: In aggregate, the
National Surveys of Drug Use and Health, 2004-2013, identified 1546 newly
incident TCS in cross-sectional research, each with standardized TCD assessment.
RESULTS: Hill function estimates contradict our apparently over-simplistic
hypothesis. Among newly incident TCS males with only 1-3 recent smoking days, an
estimated 1%-3% had become rapid-onset TCD cases; non-overlapping confidence
intervals show lower TCD risk for females. In contrast, among daily smokers,
closer to 50% of female TCS showed rapid-onset TCD, versus under 20% of male TCS,
but a larger sample will be needed to confirm the apparent female excess risk at
the daily smoking frequency level. CONCLUSIONS: Smoking frequency and TCD onset
become inter-dependent quite soon after TCS onset. Feedback loops are expected,
and might explain a potential reversal of male-female differences across smoking
frequency gradients. These novel epidemiological estimates prompt new thinking
and questions about interventions. IMPLICATIONS: In this large sample
epidemiological study, with a nationally representative sample of newly incident
TCS assessed cross-sectionally, we see a quite rapid onset of tobacco dependence,
with an early male excess that fades out at higher levels of smoking frequency.
Next steps include development of outreach and intervention for this very rapid
onset tobacco dependence.
PMID- 27613942
TI - Characteristics of American Indian/Alaskan Native Quitline Callers Across 14
States.
AB - BACKGROUND: American Indians and Alaska Natives (AI/AN) have the highest smoking
prevalence (29.2%) of any other racial/ethnic group in the United States and
lower quit rates. Comprehensive health care services, including commercial
tobacco cessation treatments, are difficult to access for many AI/AN individuals
due to poverty, the rural distribution of tribal territories, cultural barriers
and the lack of funding for these programs. Due, in part, to these health care
gaps, AI/AN communities are disproportionally affected by nicotine dependence and
associated chronic medical and psychiatric conditions. METHODS: We report on data
from National Jewish Health that provides telephonic tobacco cessation services
for 14 states in the United States. We examine how AI/AN callers who were
predominately AI callers differ from their counterparts (i.e., callers
identifying as other ethnic groups) in terms of demographic characteristics,
commercial tobacco use history, rates of emotional or mental health issues, and
rates of chronic illness. RESULTS: Findings from the quitline analyses show a
higher rate of preadolescent onset of commercial tobacco use in the AI/AN
callers. AI/AN callers are also more likely to live with another commercial
tobacco user. Results demonstrate that AI/AN callers are disproportionately
impacted by mental health challenges, including high levels of stress, anxiety,
and depression. Similarly, AI/AN callers report more chronic medical issues
including diseases of the lungs and cardiovascular system. CONCLUSIONS: These
findings stress the critical need for tailored efforts to better reach AI/AN
commercial tobacco users who are considering treatment, in order to make
meaningful gains in commercial tobacco cessation for this vulnerable population.
IMPLICATIONS: These findings demonstrate the disproportionate impact of
commercial tobacco use on the AI/AN population who utilizes quitline services.
These data stress the critical need for tailored efforts to better reach AI/AN
commercial tobacco users who are considering treatment, in order to make
meaningful gains in commercial tobacco cessation for this vulnerable population.
PMID- 27613943
TI - "They're Pretty Much Made for Blunts": Product Features That Facilitate Marijuana
Use Among Young Adult Cigarillo Users in the United States.
AB - Introduction: Cigarillo use is prevalent among young adults in the United States.
Many young people use cigarillos as "blunts," a term for a cigar emptied of its
tobacco and replaced with marijuana. Because cigars in the United States are not
subject to the same regulations as cigarettes, they offer a diverse selection of
flavors and packaging styles. It is unclear how these and other product
attributes facilitate blunt use. Methods: Semi-structured telephone interviews
were conducted with a sample of 40 young adult cigar or cigarillo users in the
United States to assess patterns of use and perceptions about product features.
Quotations from interview transcripts were coded for major themes and summarized
across participants. Results: Regardless of their preferred brand, participants
felt that the brand Black & Mild is primarily smoked for the tobacco. There was a
strong perception, however, that other popular cigarillo brands are almost always
used to make blunts. Participants believed that cigarillo companies design their
products to simplify blunt-making, with features such as perforated lines or
wrappings that unroll easily. Resealable foil pouches, a popular packaging style,
are often used to hold unused marijuana and mask its smell. Conclusions: Blunt
use is pervasive among young adult cigarillo users in the United States, and
certain cigar companies have developed products that facilitate blunt-making.
Future surveillance measures should capture the extent to which cigarillo users
are using these products as blunts. Continued surveillance of cigarillo sales and
popular product attributes are needed. Implications: Cigarillo use is prevalent
among young adults in the United States, many of whom are using the products as
blunts. This study found that product features such as brand, flavor, packaging,
and price influence the selection of cigarillos used for this purpose. There is
also a strong perception among young adult cigarillo users that cigarillo
companies design their products and packaging to make the blunt-making process
simple and enjoyable. Better surveillance measures are needed to capture the
extent to which cigarillos are used as blunts and which product features are
driving category growth.
PMID- 27613944
TI - E-Cigarettes Use Behavior and Experience of Adults: Qualitative Research Findings
to Inform E-Cigarette Use Measure Development.
AB - OBJECTIVES: To gain a better understanding of electronic cigarette (e-cigarette)
use behavior and experience among adult e-cigarette users, with the goal of
informing development of future e-cigarette use measures. METHODS: Between August
and October 2014 six focus groups were conducted in Seattle. Participants (63%
male; 60% >35 years old; 60% White): e-cigarette users who used combustible
tobacco products either currently or in the past. E-cigarette discussion topics
covered: their daily use pattern (eg, frequency), product-related characteristics
(eg, nicotine levels), and perceptions about health risks and benefits. RESULTS:
Participants' descriptions of daily use were so varied that no common "unit" of a
"session" easily summarized frequency or quantity of typical e-cigarette use.
Most users had difficulty in tracking their own use. Participants reported
nicotine craving relief when using e-cigarettes, but described e-cigarettes use
as less satisfying than combustible cigarettes. Valued characteristics included
"ready availability" and the possibility of using indoors. A unique aspect of the
e-cigarette use experience is the option of adding flavors and having the ability
to exhale "big clouds" of vapor/aerosol. Most perceived e-cigarettes as a better
and safer alternative to conventional cigarettes, yet still sought further
information about health consequences and safety of e-cigarettes from trusted
sources. CONCLUSIONS: E-cigarettes users are far from homogeneous in their
behavior and motivation for adopting e-cigarettes. A range of use patterns
arising from both hedonic and utilitarian factors, along with product
characteristics (eg, variable nicotine levels and flavors) extending beyond those
of conventional cigarettes, suggest that new, specific e-cigarette use measures
must be developed. IMPLICATIONS: The current study provides timely information on
adult e-cigarette use behavior, which is a crucial step in measuring this new
phenomenon and assessing the risks associated with using e-cigarette products.
Our findings reveal that vaping is not a mere replacement for combustible
cigarette smoking and that many users of e-cigarettes enjoy product
characteristics such as flavors and "clouds" that are unavailable in combustible
cigarettes. Therefore, commonly available cigarette smoking measures are not well
suited to measurement of e-cigarette use behavior, and indication that new
measures need to be developed to accurately track e-cigarette use.
PMID- 27613945
TI - Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E
liquids.
AB - Introduction: Most electronic cigarettes (e-cigarettes) contain a solution of
propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and
their associated e-liquids are available in numerous flavor varieties. A subset
of the flavor varieties include coffee, tea, chocolate, and energy drink, which,
in beverage form, are commonly recognized sources of caffeine. Recently, some
manufacturers have begun marketing e-liquid products as energy enhancers that
contain caffeine as an additive. Methods: A Gas Chromatography-Mass Spectrometry
(GC-MS) method for the quantitation of caffeine in e-liquids was developed,
optimized and validated. The method was then applied to assess caffeine
concentrations in 44 flavored e-liquids from cartridges, disposables, and refill
solutions. Products chosen were flavors traditionally associated with caffeine
(ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or
labeled as caffeine-containing by the manufacturer. Results: Caffeine was
detected in 42% of coffee-flavored products, 66% of tea-flavored products, and
50% of chocolate-flavored e-liquids (limit of detection [LOD] - 0.04 ug/g).
Detectable caffeine concentrations ranged from 3.3 ug/g to 703 ug/g. Energy drink
flavored products did not contain detectable concentrations of caffeine. Eleven
of 12 products marketed as energy enhancers contained caffeine, though in widely
varying concentrations (31.7 ug/g to 9290 ug/g). Conclusions: E-liquid flavors
commonly associated with caffeine content like coffee, tea, chocolate, and energy
drink often contained caffeine, but at concentrations significantly lower than
their dietary counterparts. Estimated daily exposures from all e-cigarette
products containing caffeine were much less than ingestion of traditional
caffeinated beverages like coffee. Implications: This study presents an optimized
and validated method for the measurement of caffeine in e-liquids. The method is
applicable to all e-liquid matrices and could potentially be used to ensure
regulatory compliance for those geographic regions that forbid caffeine in e
cigarette products. The application of the method shows that caffeine
concentrations and estimated total caffeine exposure from e-cigarette products is
significantly lower than oral intake from beverages. However, because very little
is known about the effects of caffeine inhalation, e-cigarette users should
proceed with caution when using caffeine containing e-cigarette products. Further
research is necessary to determine associated effects from inhaling caffeine.
PMID- 27613948
TI - Cigarette Purchasing Patterns, Readiness to Quit, and Quit Attempts Among
Homeless Smokers.
AB - Introduction: Cigarette purchasing patterns may be linked with greater readiness
to make a quit attempt and more quit attempts among domiciled samples. However,
little is known about the cigarette purchasing patterns of homeless smokers or
their potential relations to quitting intention and behaviors. This study
redressed this gap among a convenience sample of homeless adult smokers from a
large shelter in Dallas, Texas. Methods: Participants (N = 207; Mage = 43; 71.5%
male) smoked >=100 cigarettes over the lifetime and endorsed current daily
smoking. Variables assessed included cigarette dependence (time to first
cigarette of the day), monthly income, quantity of cigarettes most recently
purchased, average money spent on cigarettes weekly, readiness/motivation to quit
smoking, and the number intentional quit attempts lasting >=24h in the past year.
Regression analyses were conducted to characterize associations of cigarette
purchasing patterns with readiness to quit and quit attempts controlling for sex,
age, cigarette dependence, and income. Results: Most participants purchased
cigarettes by the pack (61.4%), and more than half the sample spent <=$20 on
cigarettes per week. Results indicated that spending less money per week on
cigarettes was associated with greater readiness to quit (P = .016), even when
controlling for income, cigarette dependence, and other covariates. Stratified
analyses indicated that this association was significant only for homeless
smokers reporting no regular monthly income. Conclusions: Homeless daily smokers
with no reported income who spend little money on cigarettes may make
particularly apt targets for cessation interventions due to potential
associations with quitting motivation. Implications: Adults who are homeless
smoke at greater rates and quit at lower rates than domiciled adults, leading to
significant smoking-related health disparities among this group. Findings suggest
that cigarette purchasing patterns are linked with readiness to quit smoking
among smokers who are homeless. Results elucidate one of the myriad factors that
contribute to tobacco-related disparities among this group and findings may have
implications for cessation interventions in homeless shelters and other contexts
where resources are limited.
PMID- 27613947
TI - Promotions on Newport and Marlboro Cigarette Packages: A National Study.
AB - Introduction: While cigarette pack designs are part of integrated marketing
efforts, it is unclear the degree to which packs are used to advertise promotions
and whether the tobacco retailers' neighborhood characteristics influence the
likelihood and type of pack-based promotion in the United States. Methods:
Between June and October 2012, data collectors purchased packs of either Marlboro
Red (n = 1090) or Newport Green (n = 1057) cigarettes at 2147 stores that were
part of a national sample of tobacco retailers in the contiguous US. Coders rated
packs for the presence of an exterior and interior pack promotion, placement of
exterior promotion (eg, front, back), presentation of exterior promotion (eg,
onsert, tear strip), and nature of the promotion (eg, contest/give/away). Using
Census tract data, we examined the association of pack promotions with tobacco
retailers' neighborhood demographic characteristics. Results: Marlboro packs were
approximately twice as likely to have promotions as Newport packs (31.7% vs.
14.7%). Fewer Marlboro packs (14.6%) and no Newport packs had interior
promotions. The majority of exterior promotions were for contests (>80% for both
brands), while almost all interior Marlboro promotions (97.5%) were for a
discounted price. There were few differences in presence or type of promotion by
tobacco retailers' neighborhood characteristics. Conclusions: Exterior packs
promotions, in particular, were fairly common and may contribute to the allure of
tobacco products. Implications: Use of promotions on the interior and exterior of
cigarette packs are a mechanism that the tobacco industry uses to sell its
products and should be continually assessed for their influence on consumer
behavior.
PMID- 27613946
TI - Supervised, Vigorous Intensity Exercise Intervention for Depressed Female
Smokers: A Pilot Study.
AB - INTRODUCTION: Few studies have evaluated exercise interventions for smokers with
depression or other psychiatric comorbidities. This pilot study evaluated the
potential role of supervised vigorous exercise as a smoking cessation
intervention for depressed females. METHODS: Thirty adult women with moderate
severe depressive symptoms were enrolled and randomly assigned to 12 weeks of
thrice weekly, in person sessions of vigorous intensity supervised exercise at a
YMCA setting (EX; n = 15) or health education (HE; n = 15). All participants
received behavioral smoking cessation counseling and nicotine patch therapy.
Assessments were done in person at baseline, at the end of 12 weeks of treatment,
and at 6 months post-target quit date. Primary end points were exercise adherence
(proportion of 36 sessions attended) and biochemically confirmed 7-day point
prevalence abstinence at Week 12. Biomarkers of inflammation were explored for
differences between treatment groups and between women who smoked and those
abstinent at Week 12. RESULTS: Treatment adherence was high for both groups (72%
for EX and 66% for HE; p = .55). The Week 12 smoking abstinence rate was higher
for EX than HE (11/15 [73%] vs. 5/15 [33%]; p = .028), but no significant
differences emerged at 6-month follow-up. Interleukin-6 levels increased more for
those smoking than women abstinent at Week 12 (p = .040). CONCLUSIONS: Vigorous
intensity supervised exercise is feasible and enhances short-term smoking
cessation among depressed female smokers. Innovative and cost-effective
strategies to bolster long-term exercise adherence and smoking cessation need
evaluation in this population. Inflammatory biomarkers could be examined in
future research as mediators of treatment efficacy. IMPLICATIONS: This
preliminary study found that vigorous intensity supervised exercise is feasible
and enhances short-term smoking cessation among depressed female smokers. This
research addressed an important gap in the field. Despite decades of research
examining exercise interventions for smoking cessation, few studies were done
among depressed smokers or those with comorbid psychiatric disorders. A novel
finding was increases in levels of a pro-inflammatory biomarker observed among
women who smoked at the end of the intervention compared to those who did not.
PMID- 27613949
TI - Analysis of State-Specific Prevalence, Regional Differences, and Correlates of
Hookah Use in U.S. Adults, 2012-2013.
AB - Objective: To investigate the state-specific prevalence, regional differences,
and correlates of hookah use among U.S. adults. Methods: We analyzed the most
recent nationally representative data of adults from the National Adult Tobacco
Survey (NATS) 2012-2013 (n = 60192). State-specific prevalence of lifetime and
current hookah use was calculated and mapped. Multivariate logistic regression
was performed to determine the association between sociodemographic
characteristics, regional differences, and hookah use. Results: Among U.S. adults
(>=18 years), overall prevalence of lifetime hookah use was 12.3%, while current
use was 3.9%. Mapping of state-specific prevalence revealed that the West tended
to have higher rates of use, while the South tended to have lower ones. In the
adjusted model, we observed that current hookah use was positively associated
with younger adults, males, non-Hispanic adults, those with higher education and
income statuses, being single, those living in the West, and current cigarette
use. Conclusion: The prevalence of hookah use varies by state, region, and
sociodemographic characteristics among adults. Future research, including
longitudinal studies, are needed to identify geographic and sociodemographic
characteristics and trends among hookah users, investigate hookah-related health
outcomes, and evaluate targeted public health efforts aimed at this emerging
threat. Implications: This study investigates state-level prevalence, regional
differences, and sociodemographic characteristics of hookah use among U.S.
adults, using the most recent NATS. Hookah use was positively associated with
younger adults and those living in the West. This study adds to the understanding
of the geographic and sociodemographic factors underlying hookah use, which can
be used to develop much needed evidence-based regulations and programs that are
responsive to the needs of different risk groups.
PMID- 27613951
TI - Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the
Tobacco Heating System 2.1.
AB - INTRODUCTION: Heating rather than burning tobacco reduces levels of harmful and
potentially harmful constituents, and consumer products using this approach aim
to reduce exposure to tobacco toxicants. The Tobacco Heating System (THS) version
2.1 has been enhanced from earlier prototypes with an improved heat control and
sensorial experience and thereby user acceptance. Exposure measurements are
required to determine whether it may be possible to reduce the individual health
risk compared to smoking combustible cigarettes (CCs). METHODS: This controlled
clinical study randomly assigned 40 smokers to either a group continuing to use
of their own CC brand (n = 20) or a group switching to THS 2.1 (n = 20) for 5
days. Biomarkers of exposure were measured at baseline and on day 1 through day
5. Product consumption, Human Puffing Topography, the occurrence of adverse
events, and an assessment of subjective effects, such as smoking satisfaction and
enjoyment of respiratory tract sensations, were also determined. RESULTS: The
group of smokers who switched to THS 2.1 adapted their puffing behavior initially
through longer puff duration and more puffs. During the duration of the study,
total puff volume returned to baseline levels and the mean daily product
consumption increased but with similar nicotine exposure compared to baseline CC
use. Biomarkers of exposure to tobacco smoke toxicants which inform product risk
assessment were significantly reduced with THS use compared to the CC group. THS
2.1 users experienced less reinforcing effects with THS 2.1 than with their own
cigarette brand. CONCLUSIONS: THS 2.1 is a promising alternative to smoking CCs.
Notwithstanding possible use adaption through consumption or puffing behavior,
the exposure to harmful smoke constituents was markedly reduced with the new
heated tobacco platform. IMPLICATIONS: Exposure markers to harmful and
potentially harmful smoke constituents were lowered with the THS 2.1. Heating
tobacco instead of burning can offer a potentially lower risk of delivering
nicotine compared to CCs.
PMID- 27613950
TI - Secondhand Smoke Exposure and Low Blood Lead Levels in Association With Attention
Deficit Hyperactivity Disorder and Its Symptom Domain in Children: A Community
Based Case-Control Study.
AB - AIM: Secondhand smoke (SHS) is a major indoor pollutant. We examined the possible
association between exposure to both SHS and low levels of lead and attention
deficit-hyperactivity disorder (ADHD) and its symptom domain in children.
METHODS: This case-control study was based on the results of a community survey
using the ADHD rating scale conducted in 49 elementary schools. Both cases and
control subjects were confirmed by a child psychiatrist. Each case was matched
with one control subject according to gender, school, and grade in school. Using
a multivariate conditional logistic regression model, we analyzed 214 case
control pairs of children who ranged in age from 6 to 10 years. Urine and blood
levels of cotinine and of lead were determined, and information pertaining to SHS
exposure was obtained by means of a questionnaire. RESULTS: Exposure to low
levels of lead (geometric mean = 1.65 ug/dL) was related to ADHD, particularly
inattention (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.07-2.59),
whereas SHS exposure was associated mainly with hyperactivity/impulsivity (OR =
3.85, 95% CI = 1.55-9.56). In the pathway from blood lead to
hyperactivity/impulsivity, children's SHS exposure mediated and indirectly
accounted for about 73% of this relationship. The combined exposure to lead and
SHS synergistically increased the risk of ADHD, evident as both inattention and
hyperactivity/impulsivity. CONCLUSION: SHS, which is associated with
hyperactivity/impulsivity in particular, combined with exposure to low blood
levels of lead synergistically increased the risk of ADHD. Therefore, the
exposure of children to both SHS and lead needs to be reduced. IMPLICATIONS:
Although exposure to low levels of lead has been shown to be associated with
ADHD, there is little evidence of symptom domain specificity. In our study, low
blood lead levels were related to inattention. In addition, prenatal or postnatal
exposure to SHS increased the risk of ADHD, particularly
hyperactivity/impulsivity. Combined exposure to lead and SHS synergistically
increased the risk for both these ADHD symptom domains. To protect children from
environmental risk factors related to ADHD, it is necessary to further reduce
children's exposure to SHS and lead, even in those with low blood lead levels.
PMID- 27613952
TI - The Application of a Decision-Theoretic Model to Estimate the Public Health
Impact of Vaporized Nicotine Product Initiation in the United States.
AB - INTRODUCTION: The public health impact of vaporized nicotine products (VNPs) such
as e-cigarettes is unknown at this time. VNP uptake may encourage or deflect
progression to cigarette smoking in those who would not have otherwise smoked,
thereby undermining or accelerating reductions in smoking prevalence seen in
recent years. METHODS: The public health impact of VNP use are modeled in terms
of how it alters smoking patterns among those who would have otherwise smoked
cigarettes and among those who would not have otherwise smoked cigarettes in the
absence of VNPs. The model incorporates transitions from trial to established VNP
use, transitions to exclusive VNP and dual use, and the effects of cessation at
later ages. Public health impact on deaths and life years lost is estimated for a
recent birth cohort incorporating evidence-informed parameter estimates. RESULTS:
Based on current use patterns and conservative assumptions, we project a
reduction of 21% in smoking-attributable deaths and of 20% in life years lost as
a result of VNP use by the 1997 US birth cohort compared to a scenario without
VNPs. In sensitivity analysis, health gains from VNP use are especially sensitive
to VNP risks and VNP use rates among those likely to smoke cigarettes.
CONCLUSIONS: Under most plausible scenarios, VNP use generally has a positive
public health impact. However, very high VNP use rates could result in net harms.
More accurate projections of VNP impacts will require better longitudinal
measures of transitions into and out of VNP, cigarette and dual use.
IMPLICATIONS: Previous models of VNP use do not incorporate whether youth and
young adults initiating VNP would have been likely to have been a smoker in the
absence of VNPs. This study provides a decision-theoretic model of VNP use in a
young cohort that incorporates tendencies toward smoking and shows that, under
most plausible scenarios, VNP use yields public health gains. The model makes
explicit the type of surveillance information needed to better estimate the
effect of new products and thereby inform public policy.
PMID- 27613954
TI - Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice.
PMID- 27613953
TI - Stigmatic and Sympathetic Attitudes Toward Cancer Patients Who Smoke: A
Qualitative Analysis of an Online Discussion Board Forum.
AB - INTRODUCTION: A significant minority of patients continue to smoke after a cancer
diagnosis. Cancer patients who smoke experience stigma that can negatively impact
health outcomes. We explored publicly shared perspectives about cancer patients
who continued to smoke post-diagnosis. METHODS: An online news article, published
in January 2012, summarized the findings of smoking prevalence among patients
with lung cancer and colorectal cancer enrolled in the Cancer Care Outcomes
Research and Surveillance Consortium trial. In response, written comments were
posted on the articles' public discussion board. Applying principles of grounded
theory, we conducted a document analysis and established a conceptual framework
to develop a model by which to explain factors underlying stigmatic and
sympathetic attitudes toward cancer survivors who continue to smoke. RESULTS:
Personal experiences with cancer, smoking, and statistical literacy were found to
influence beliefs about cancer and smoking, which in turn influenced stigmatic or
sympathetic attitudes. More sympathetic attitudes were expressed by individuals
who had personal experiences with smoking, believed cancer is multicausal,
identified smoking as an addiction, or considered extrinsic factors responsible
for smoking. Individuals who did not have personal experiences with cancer or
smoking, had low statistical literacy, believed that smoking necessarily and
directly causes cancer, and focused on intrinsic responsibilities for smoking
tended to express more stigmatic attitudes. CONCLUSIONS: The current findings
raise awareness and provide insight into stigma against cancer survivors who
smoke and can help inform strategies for reducing stigma against this vulnerable
group. IMPLICATIONS: This study helps raise awareness of stigma toward cancer
patients who smoke and provides insight into the processes that may influence
stigmatic as compared to sympathetic attitudes toward these patients. Results
suggest that population-based strategies to educate the public regarding the
nature of nicotine addiction, difficulty of quitting, and benefits of quitting
for cancer patients may be useful for reducing stigma against cancer patients
with a smoking history.
PMID- 27613955
TI - Palmitoylation of the human prostacyclin receptor. FUNCTIONAL IMPLICATIONS OF
PALMITOYLATION AND ISOPRENYLATION.
PMID- 27613956
TI - The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a
target for nitric oxide-mediated desensitization. INDEPENDENT MODULATION OF
TPalpha SIGNALING BY NITRIC OXIDE AND PROSTACYCLIN.
PMID- 27613957
TI - A Loyal Friend of ASBMB and JBC: Howard Schachman, 1918-2016.
PMID- 27613958
TI - Electronic Cigarettes and Smoking Cessation.
PMID- 27613967
TI - Polydatin protects cardiomyocytes against myocardial infarction injury by
activating Sirt3.
AB - Myocardial infarction (MI), which is characterized by chamber dilation and left
ventricular (LV) dysfunction, represents a major cause of morbidity and mortality
worldwide. Polydatin (PD), a monocrystalline and polyphenolic drug isolated from
a traditional Chinese herb (Polygonum cuspidatum), alleviates mitochondrial
dysfunction. We investigated the effects and underlying mechanisms of PD in post
MI cardiac dysfunction. We constructed an MI model by left anterior descending
(LAD) coronary artery ligation using wild-type (WT) and Sirt3 knockout (Sirt3-/-)
mice. Cardiac function, cardiomyocytes autophagy levels, apoptosis and
mitochondria biogenesis in mice that underwent cardiac MI injury were compared
between groups. PD significantly improved cardiac function, increased autophagy
levels and decreased cardiomyocytes apoptosis after MI. Furthermore, PD improved
mitochondrial biogenesis, which is evidenced by increased ATP content, citrate
synthase (CS) activity and complexes I/II/III/IV/V activities in the
cardiomyocytes subjected to MI injury. Interestingly, Sirt3 knockout abolished
the protective effects of PD administration. PD inhibited apoptosis in cultured
neonatal mouse ventricular myocytes subjected to hypoxia for 6h to simulate MI
injury. PD increased GFP-LC3 puncta, and reduced the accumulation of protein
aggresomes and p62 in cardiomyocytes after hypoxia. Interestingly, the knock-down
of Sirt3 nullified the PD-induced beneficial effects. Thus, the protective
effects of PD are associated with the up-regulation of autophagy and improvement
of mitochondrial biogenesis through Sirt3 activity.
PMID- 27613969
TI - Novel identification of biofluids using a multiplex methylation sensitive
restriction enzyme-PCR system.
AB - The identification of a specific body fluid encountered in a forensic
investigation can give crucial information. This identification can be aided by
methylation profiles based on selected markers specific to a range of biofluids.
In this study, the open database of Infinium HumanMethylation450 BeadChip was
searched for markers specific for semen, vaginal fluids, saliva, venous blood and
menstrual blood. A total of 8 biofluid-specific methylated markers and 2 control
markers were combined into a 10-plex methylation sensitive restriction enzyme-PCR
(MSRE-PCR) system. Based upon the analysis of 100 DNA samples from these 5
biofluid types, unambiguous results were obtained to identify the body fluid from
which it originated. Validation studies of the developed 10-plex MSRE-PCR
included sensitivity, reproducibility and mixed body fluids. Co-amplification of
the established MSRE-PCR system and the microsatellite loci in AmpFlSTR(r)
MiniFilerTM PCR Amplification Kit was performed to generate both the methylation
profile for biofluid type and the miniSTR profile. This allowed human
identification and the identification of the body fluid type to be performed in a
single reaction. The results of this study displayed the applicability of this 10
plex MSRE-PCR system in forensic science.
PMID- 27613968
TI - What happened to the HIV epidemic among non-injecting drug users in New York
City?
AB - BACKGROUND AND AIMS: HIV has reached high prevalence in many non-injecting drug
user (NIDU) populations. The aims of this study were to (1) examine the trend in
HIV prevalence among non-injecting cocaine and heroin NIDUs in New York City, (2)
identify factors potentially associated with the trend and (3) estimate HIV
incidence among NIDUs. DESIGN: Serial-cross sectional surveys of people entering
drug treatment programs. People were permitted to participate only once per year,
but could participate in multiple years. SETTING: Mount Sinai Beth Israel drug
treatment programs in New York City, USA. PARTICIPANTS: We recruited 3298 non
injecting cocaine and heroin users from 2005 to 2014. Participants were 78.7%
male, 6.1% white, 25.7% Hispanic and 65.8% African American. Smoking crack
cocaine was the most common non-injecting drug practice. MEASURES: Trend tests
were used to examine HIV prevalence, demographics, drug use, sexual behavior and
use of antiretroviral treatment (ART) by calendar year; chi2 and multivariable
logistic regression were used to compare 2005-10 versus 2011-14. FINDINGS: HIV
prevalence declined approximately 1% per year (P < 0.001), with a decline from
16% in 2005-10 to 8% in 2011-14 (P < 0.001). The percentages of participants
smoking crack and having multiple sexual partners declined and the percentage of
HIV-positive people on ART increased. HIV incidence among repeat participants was
1.2 per 1000 person-years (95% confidence interval = 0.03/1000-7/1000).
CONCLUSIONS: HIV prevalence has declined and a high percentage of HIV-positive
non-injecting drug users (NIDUs) are receiving antiretroviral treatment,
suggesting an end to the HIV epidemic among NIDUs in New York City. These results
can be considered a proof of concept that it is possible to control non-injecting
drug use related sexual transmission HIV epidemics.
PMID- 27613970
TI - TriXY-Homogeneous genetic sexing of highly degraded forensic samples including
hair shafts.
AB - Sexing of biological evidence is an important aspect in forensic investigations.
A routinely used molecular-genetic approach to this endeavour is the amelogenin
sex test, which is integrated in most commercially available polymerase chain
reaction (PCR) kits for human identification. However, this assay is not entirely
effective in respect to highly degraded DNA samples. This study presents a
homogeneous PCR assay for robust sex diagnosis, especially for the analysis of
severely fragmented DNA. The introduced triplex for the X and Y chromosome
(TriXY) is based on real-time PCR amplification of short intergenic sequences
(<50bp) on both gonosomes. Subsequent PCR product examination and molecular
genetic sex-assignment rely on high-resolution melting (HRM) curve analysis.
TriXY was optimized using commercially available multi-donor human DNA
preparations of either male or female origin and successfully evaluated on
challenging samples, including 46 ancient DNA specimens from archaeological
excavations and a total of 16 DNA samples extracted from different segments of
eight hair shafts of male and female donors. Additionally, sensitivity and cross
species amplification were examined to further test the assay's utility in
forensic investigations. TriXY's closed-tube format avoids post-PCR sample
manipulations and, therefore, distinctly reduces the risk of PCR product carry
over contamination and sample mix-up, while reducing labour and financial
expenses at the same time. The method is sensitive down to the DNA content of
approximately two diploid cells and has proven highly useful on severely
fragmented and low quantity ancient DNA samples. Furthermore, it even allowed for
sexing of proximal hair shafts with very good results. In summary, TriXY
facilitates highly sensitive, rapid, and costeffective genetic sex-determination.
It outperforms existing sexing methods both in terms of sensitivity and minimum
required template molecule lengths. Therefore, we feel confident that TriXY will
prove to be a reliable addition to the toolbox currently used for sex-typing in
forensic genetics and other fields of research.
PMID- 27613971
TI - Growing Evidence Linking OSA During Rapid Eye Movement Sleep to Systemic
Hypertension.
PMID- 27613972
TI - Platelet Activation Testing for Heparin-Induced Thrombocytopenia Antibodies: A
Problem That Needs Fixing?
PMID- 27613973
TI - Alveolar Type 2 Cell Transplantation in IPF: Recreating the Silver Lining.
PMID- 27613974
TI - The Ultrasound Corner Series: A Reverberating Success.
PMID- 27613975
TI - Measuring Eosinophils to Make Treatment Decisions in Asthma.
PMID- 27613978
TI - Response.
PMID- 27613979
TI - Nurse Practitioners Cannot Handle Complex ICU Patients.
PMID- 27613980
TI - A Scoring Application for the St. George's Respiratory Questionnaire.
PMID- 27613981
TI - Familial Chronic Thromboembolic Pulmonary Hypertension in a Pair of Japanese
Brothers.
PMID- 27613982
TI - Unheated or No Humidification Bubble for Long-Term Nasal Low-Flow Oxygen: A
Matter of Nasal Mucosa Response or Disease Progression.
PMID- 27613983
TI - Response.
PMID- 27613984
TI - Evaluating Outcomes Disparities in the Hispanic Cystic Fibrosis Population: A
Need for a National Analysis.
PMID- 27613985
TI - Response.
PMID- 27613986
TI - Autoantibodies Are Already Found in Connective Tissue Disease-Associated
Interstitial Lung Disease.
PMID- 27613987
TI - Bisphosphonates and Atrial Fibrillation in Elderly Men: Casual or Causal
Association?
PMID- 27613988
TI - Response.
PMID- 27613990
TI - Response.
PMID- 27613989
TI - What Is the Appropriate Therapy for Community-Acquired Pseudomonas Aeruginosa
Pneumonia?
PMID- 27613991
TI - Severe Pulmonary Fibrosis as the First Manifestation of Interferonopathy (TMEM173
Mutation).
AB - We report three cases of pulmonary disease suggesting fibrosis in two familial
and one sporadic case. Pulmonary symptoms were associated with various clinical
features of systemic inflammation and vasculitis involving the skin, and appeared
at different ages. A strong interferon signature was found in all three cases.
Disease was not responsive to corticosteroids, and lung transplantation was
considered for all three subjects at an early age. One of them underwent double
lung transplantation, but she immediately experienced a primary graft dysfunction
and died soon after. Recognized causes of familial interstitial lung disease were
all excluded. All three subjects had a mutation in the previously described
autoinflammatory disease called SAVI (stimulator of interferon genes [STING]
associated vasculopathy with onset in infancy). These cases emphasize the need to
consider this possibility in children and young adults with lung fibrosis after
common causes have been ruled out.
PMID- 27613992
TI - A 50-Year-Old Woman With a History of Hypertension and Tobacco Use Presenting
With Hypoxia.
PMID- 27613993
TI - Fever in a Young Female: Unmasking a Rare Disaster.
PMID- 27613994
TI - Ten Years of Chronic Cough in a 64-Year-Old Man With Multiple Pulmonary Nodules.
AB - A 64-year-old male former smoker with a history of prostate cancer presented to
our pulmonary clinic, complaining of nonproductive cough for 10 years. Prior
evaluation included treatment for upper airway cough syndrome and
gastroesophageal reflux, stopping angiotensin-converting enzyme inhibitor, and
initiation of inhaled beta-agonists. Esophageal pH monitoring indicated silent
reflux, and proton pump inhibitor therapy was started. He continued to cough and
complain of dyspnea. Physical examination produced unremarkable results, with no
evidence of lymphadenopathy. Pulmonary function tests showed a pseudo-restrictive
pattern with air trapping, hyperreactivity, and incomplete bronchodilator
responsiveness: FEV1, 2.48 L (69% of predicted); FVC, 3.57 L (75% of predicted);
FEV1/FVC, 92%; total lung capacity, 7.00 L (100% of predicted); and residual
volume, 3.05 L (136% of predicted). Laboratory studies, including a complete
metabolic panel, prostate-specific antigen test, and complete blood count,
yielded normal results.
PMID- 27613995
TI - A 34-Year-Old Pregnant Woman With Cough, Chest Pain, and a Left Upper Lobe Mass.
AB - A 34-year-old white woman who was 30 weeks' pregnant initially presented to her
primary care physician with a cough for which she was given antibiotics, but she
had persistent symptoms. These were followed by chest pain, as a result of which
she was referred to our department. She had a past medical history of
hypertension, and currently was in her sixth pregnancy, with no reported
complications in the previous pregnancies. Review of systems was otherwise
negative. She had a three-pack-year smoking history, but denied smoking during
her current pregnancy.
PMID- 27613996
TI - F-18 FDG PET/CT imaging of cardiac and vascular inflammation and infection.
AB - INTRODUCTION: Inflammation forms an important core of the aetiopathogenic process
involved in many diseases affecting the heart and the blood vessels. These
diseases include infections as well as inflammatory non-infectious cardiovascular
conditions. The common feature of this is invasion of the heart or blood vessel
by inflammatory cells. F-18 2-fluoro 2-deoxy-D glucose (FDG) is an analogue of
glucose and like glucose it is taken up by activated inflammatory cells that
accumulate at the site of infection. This has formed the basis of the use of F-18
FDG PET/CT in the non-invasive evaluation of human inflammatory diseases. SOURCES
OF DATA: This review is based on the published academic articles as well as our
clinical experience. AREAS OF AGREEMENT: F-18 FDG PET/CT is a useful imaging
modality in the evaluation of cardiovascular inflammatory disorders. Accumulation
and distribution of F-18 FDG at the site of inflammation/infection corresponds to
severity of the inflammation/infection and extent of involvement. AREAS OF
CONTROVERSY: Most studies evaluating utility of F-18 FDG PET/CT in imaging
cardiovascular inflammation are small observational studies hence are potentially
prone to bias. GROWING POINTS: Being a hybrid metabolic and morphologic imaging
technique, F-18 FDG PET/CT offers combined advantage of complementary anatomic
and metabolic information in disease process. This makes it a useful modality in
the diagnosis, determination of extent of disease, prognostication as well as
treatment monitoring. AREAS TIMELY FOR DEVELOPING RESEARCH: Larger prospective
studies are needed to validate the superiority of F-18 FDG PET/CT imaging over
conventional anatomic imaging modalities.
PMID- 27613998
TI - Gadolinium deposition in the brain.
AB - Gadolinium is highly toxic. Gadolinium-based contrast agents (GBCAs) consist of
gadolinium ions and a chelating agent that binds the gadolinium ion tightly in
order not to manifest its toxicity. Knowledge regarding gadolinium deposition in
patients with normal renal function has advanced dramatically. Since 2014,
increasing attention has been given to residual gadolinium known to accumulate in
the tissues of patients with normal renal function. High signal intensity on T1
weighted images (T1WI) in the dentate nucleus, globus pallidus, and pulvinar
region of the thalamus correlate roughly with the number of previous GBCA
administrations. Pathological analyses have revealed that residual gadolinium is
deposited not only in these brain regions, but also in extracranial tissues such
as liver, skin and bone. The risks attendant with these deposits are unknown.
Common sense dictates that gadolinium deposition be kept as low as possible, and
that gadolinium contrast agents be used only when absolutely necessary, with
preferential use of macrocyclic chelates, which seem to be deposited at lower
concentrations.
PMID- 27613997
TI - Achromatic temporal-frequency responses of human lateral geniculate nucleus and
primary visual cortex.
AB - The sensitivity of the sensory systems to temporal changes of the environment
constitutes one of the critical issues in perception. In the present study, we
investigated the human early visual system's dependency on the temporal frequency
of visual input using fMRI. Blood oxygen level-dependent (BOLD) responses of the
lateral geniculate nucleus (LGN) and primary visual cortex (V1) were investigated
in a wide frequency range (6-46Hz) with fine frequency sampling (13 frequencies).
Subject-specific functional-anatomic ROIs were derived from the combination of
the anatomic template masks and the functional maps derived from multi-session
fMRI analyses across all 13 stimulation conditions. Using functional-anatomic
ROIs, average responses of LGN and V1 were calculated for each frequency. The V1
surface area was further parsed into 7 eccentricity sectors to detail central and
peripheral responses. LGN's response revealed fluctuations on a background of non
significant decrease of the BOLD response with increasing stimulation frequency,
while V1 response displayed similar fluctuations with a global maximum in the
range of 8-12Hz, but a rapid and significant decrease with increasing stimulation
frequency especially above 14Hz. This behavior of V1 response valid for both
central and peripheral vision emphasizes that the profound low-pass effect of the
visual system to visual input emerges in V1, presumably generated by the intra
cortical circuitry of V1 or projections from extra-striate areas. Besides, the
high correlation between LGN and V1 BOLD responses across all visual stimulation
frequencies supports the oscillatory tuning in thalamo-cortical interactions as
previously claimed in electrophysiological studies.
PMID- 27613999
TI - PDT and emerging therapies for Actinic Keratosis-A resource letter.
AB - Aktinic Keratosis is common and if left untreated may develop into life
threatening squamous cell carcinoma. Therefore early intervention is the standard
of care. While many treatments are available PDT continues to move to the for -
front for this indication (Brito et al., 2016 [31]). Topical PS is commercially
available that are able to reliably ablate these lesions. Innovative protocols
including sunlight, large volume LED arrays and maneuvers to improve treatment
parameters and cosmesis continue to make this a worldwide treatment of choice for
AK.
PMID- 27614000
TI - Sensing of dangerous DNA.
AB - The presence of damaged and microbial DNA can pose a threat to the survival of
organisms. Cells express various sensors that recognize specific aspects of such
potentially dangerous DNA. Recognition of damaged or microbial DNA by sensors
induces cellular processes that are important for DNA repair and inflammation.
Here, we review recent evidence that the cellular response to DNA damage and
microbial DNA are tightly intertwined. We also discuss insights into the
parameters that enable DNA sensors to distinguish damaged and microbial DNA from
DNA present in healthy cells.
PMID- 27614001
TI - Cardiac Sarcoidosis: The Impact of Age and Implanted Devices on Survival.
AB - OBJECTIVE: To assess the clinical characteristics, diagnosis, and outcome of
cardiac sarcoidosis in a single institution sarcoidosis clinic. METHODS: Patients
with cardiac sarcoidosis were identified using refined World Association of
Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria of highly probable
and probable. Patient demographics, local and systemic treatments, and clinical
outcome were collected. RESULTS: Of the 1,815 patients evaluated over a 6-year
period, 73 patients met the WASOG criteria for cardiac sarcoidosis. The median
age at diagnosis was 46 years, with a median follow-up of 8.8 years. Reduced left
ventricular ejection fraction (LVEF) was the most common manifestation (54.8%).
Patients with arrhythmias experienced ventricular tachycardia or severe heart
block, (35.6% and 19.2%, respectively) with or without reduced LVEF. A total of
45 (61.6%) patients underwent cardiac PET scan and/or MRI, with 41 (91.1%) having
a positive study. During follow-up, 10 patients (13.7%) either underwent
transplant (n = 3) or died (n = 7) from sarcoidosis. Kaplan-Meier survival curves
revealed 5- and 10-year survival rates of 95.5% and 93.4%, respectively.
Univariate factors of age at diagnosis < 46 years, implantation of pacemaker or
defibrillator, mycophenolate treatment, or LVEF > 40% were associated with
improved survival. Cox regression analysis demonstrated that age >= 46 years and
lack of an implanted pacemaker or defibrillator were the only independent
predictors of mortality. CONCLUSIONS: The new WASOG criteria were able to
characterize cardiac involvement in our sarcoidosis clinic. Age and lack of
pacemaker or defibrillator were the significant predictors of mortality for
cardiac sarcoidosis, and reduced LVEF < 40% was associated with worse prognosis.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02356445; URL:
www.clinicaltrials.gov.
PMID- 27614003
TI - 3D-printed head models for navigated non-invasive brain stimulation.
PMID- 27614004
TI - Effect of continuous positive airway pressure on liver enzymes in obstructive
sleep apnea: A meta-analysis.
AB - BACKGROUND: Previous studies have suggested that obstructive sleep apnea (OSA)
was associated with nonalcoholic fatty liver disease (NAFLD). However, the impact
of OSA treatment using continuous positive airway pressure (CPAP) on liver
enzymes remained controversial. This meta-analysis was conducted to determine
whether CPAP therapy could reduce liver enzyme levels. METHODS: Two reviewers
independently searched PubMed, Cochrane library, Embase and Web of Science before
December 2015. Information on characteristics of subjects, study design and pre-
and post-CPAP treatment of serum ALT and AST was extracted for analysis. A total
of five studies with seven cohorts that included 192 patients were pooled into
meta-analysis. RESULTS: CPAP was associated with a statistically significant
decrease on both ALT and AST levels in OSA patients (WMD = 8.036, 95% CI = 2.788
13.285, z = 3.00, P = .003 and WMD = 4.612, 95% CI = 0.817-8.407, z = 2.38, P =
.017, respectively). Subgroup analyses indicated that CPAP therapy was more
effective in OSA patients with treatment duration > 3 mo (WMD = 12.374, 95% CI =
2.727-22.020, z = 2.51, P = .012 for ALT and WMD = 7.576, 95% CI = 1.781-13.370,
z =2.56, P = .010 for AST). CONCLUSION: This meta-analysis suggested that CPAP
was associated with a statistically significant decrease on liver enzymes in OSA
patients. Further large-scale well-designed RCTs with long-term follow-up are
required to clarify this issue.
PMID- 27614002
TI - Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and
Expert Panel Report.
AB - BACKGROUND: We updated the 2006 ACCP clinical practice guidelines for management
of reflux-cough syndrome. METHODS: Two population, intervention, comparison,
outcome (PICO) questions were addressed by systematic review: (1) Can therapy for
gastroesophageal reflux improve or eliminate cough in adults with chronic and
persistently troublesome cough? and (2) Are there minimal clinical criteria to
guide practice in determining that chronic cough is likely to respond to therapy
for gastroesophageal reflux? RESULTS: We found no high-quality studies pertinent
to either question. From available randomized controlled trials (RCTs) addressing
question #1, we concluded that (1) there was a strong placebo effect for cough
improvement; (2) studies including diet modification and weight loss had better
cough outcomes; (3) although lifestyle modifications and weight reduction may be
beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs)
demonstrated no benefit when used in isolation; and (4) because of potential
carryover effect, crossover studies using PPIs should be avoided. For question
#2, we concluded from the available observational trials that (1) an algorithmic
approach to management resolved chronic cough in 82% to 100% of instances; (2)
cough variant asthma and upper airway cough syndrome (UACS) (previously referred
to as postnasal drip syndrome) from rhinosinus conditions were the most commonly
reported causes; and (3) the reported prevalence of reflux-cough syndrome varied
widely. CONCLUSIONS: The panelists (1) endorsed the use of a
diagnostic/therapeutic algorithm addressing causes of common cough, including
symptomatic reflux; (2) advised that although lifestyle modifications and weight
reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated
no benefit when used in isolation; and (3) suggested that physiological testing
be reserved for refractory patients being considered for antireflux surgery or
for those in whom there is strong clinical suspicion warranting diagnostic
testing.
PMID- 27614005
TI - Assessing neuronal density in peri-infarct cortex with PET: Effects of cortical
topology and partial volume correction.
AB - The peri-infarct cortex (PIC) is the site of long-term physiologic changes after
ischemic stroke. Traditional methods for delineating the peri-infarct gray matter
(GM) have used a volumetric Euclidean distance metric to define its extent around
the infarct. This metric has limitations in the case of cortical stroke, i.e.,
those where ischemia leads to infarction in the cortical GM, because the
vascularization of the cerebral cortex follows the complex, folded topology of
the cortical surface. Instead, we used a geodesic distance metric along the
cortical surface to subdivide the PIC into equidistant rings emanating from the
infarct border and compared this new approach to a Euclidean distance metric
definition. This was done in 11 patients with [F-18]-Flumazenil ([18-F]-FMZ)
positron emission tomography (PET) scans at 2 weeks post-stroke and at 6 month
follow-up. FMZ is a PET radiotracer with specific binding to the alpha subunits
of the type A gamma-aminobutyric acid (GABAA) receptor. Additionally, we used
partial-volume correction (PVC) of the PET images to compensate for potential
cortical thinning and long-term neuronal loss in follow-up images. The difference
in non-displaceable binding potential (BPND ) between the stroke unaffected and
affected hemispheres was 35% larger in the geodesic versus the Euclidean peri
infarct models in initial PET images and 48% larger in follow-up PET images. The
inter-hemispheric BPND difference was approximately 17-20% larger after PVC when
compared to uncorrected PET images. PET studies of peri-infarct GM in cortical
strokes should use a geodesic model and include PVC as a preprocessing step. Hum
Brain Mapp 38:326-338, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27614006
TI - Downregulation of glutamatergic and GABAergic proteins in valproric acid
associated social impairment during adolescence in mice.
AB - The etiology of Autism Spectrum Disorder (ASD) remains controversial. Deficits in
social communication are one of the key criteria for ASD diagnosis. Valproic acid
(VPA), which is an anti-epileptic and anti-depressive drug, is one of the
teratogens to cause ASD onset. Moreover, synaptic dysfunction is suggested as one
of the major causative factor in VPA-induced ASD in vitro and in vivo studies.
Herein, this study aimed to determine the excitatory/inhibitory synaptic mRNA and
protein expression in VPA-induced autistic mice. Pregnant BALB/c mice were
injected peritoneally with a single dose of 600mg/kg VPA on embryonic day (E)
12.5. Social impairment was verified by three chamber sociability tests on
postnatal days (PND) 28, 35, 42 and 49. Cortical synaptic mRNA and protein
expressions were examined on PND 50. The excitatory synaptic proteins NR2A, NR2B,
NR2C were significantly down-regulated by 80.0% (p<0.01), 51.5% (p<0.05) and
81.5% (p<0.05) respectively. Furthermore, the NMDAR expression regulatory protein
BDNF was also found to be significantly downregulated by 76.8% (p<0.05). GAD65,
GAD67, GABRA1, GABRA5, GABRB2 from the GABAergic inhibitory synaptic pathway were
significantly downregulated by 21.3% (p<0.05), 77.0% (p<0.05), 53.9% (p<0.05),
56.9% (p<0.05) and 55.2% (p<0.01) respectively in the cortex of VPA-induced mice.
Taken together, our results suggested that synaptic dysfunction might be involved
in the social impairments in VPA-induced ASD.
PMID- 27614008
TI - Macrophage fatty acid oxidation and its roles in macrophage polarization and
fatty acid-induced inflammation.
AB - Recent research considerably changed our knowledge how cellular metabolism
affects the immune system. We appreciate that metabolism not only provides energy
to immune cells, but also actively influences diverse immune cell phenotypes.
Fatty acid metabolism, particularly mitochondrial fatty acid oxidation (FAO)
emerges as an important regulator of innate and adaptive immunity. Catabolism of
fatty acids also modulates the progression of disease, such as the development of
obesity-driven insulin resistance and type II diabetes. Here, we summarize (i)
recent developments in research how FAO modulates inflammatory signatures in
macrophages in response to saturated fatty acids, and (ii) the role of FAO in
regulating anti-inflammatory macrophage polarization. In addition, we define the
contribution of AMP-activated protein kinase (AMPK) and peroxisome proliferator
activated receptors (PPARs), in controlling macrophage biology towards fatty acid
metabolism and inflammation.
PMID- 27614007
TI - Training of the impaired forelimb after traumatic brain injury enhances
hippocampal neurogenesis in the Emx1 null mice lacking a corpus callosum.
AB - Unilateral brain injury is known to disrupt the balance between the two cortices,
as evidenced by an abnormally high interhemispheric inhibitory drive from motor
cortex M1intact to M1lesioned transmitted transcallosally. Our previous work has
shown that the deletion of homeobox gene Emx1 not only led to the agenesis of the
corpus callosum (cc), but also to reduced hippocampal neurogenesis. The current
study sought to determine whether lacking the cc affected the recovery of
forelimb function and hippocampal plasticity following training of the affected
limb in mice with unilateral traumatic brain injuries (TBI). One week after TBI,
produced by a controlled cortical impact to impair the preferred limb, Emx1 wild
type (WT) and knock out (KO) mice were subjected to the single-pellet reaching
task with the affected limb for 4 weeks. Both TBI and Emx1 deletion had overall
adverse effects on the successful rate of reaching. However, TBI significantly
affected reaching performance only in the WT mice and not in the KO mice. Both
TBI and Emx1 gene deletion also negatively affected hippocampal neurogenesis,
demonstrated by a reduction in doublecortin (DCX)-expressing immature neurons,
while limb training enhanced DCX expression. However, limb training increased DCX
cells in KO mice only in the TBI-treated group, whereas it induced neurogenesis
in both WT mice groups regardless of the treatment. Our finding also suggests
that limb training enhances neuroplasticity after brain injury at functionally
remote regions including the hippocampus, which may have implications for
promoting overall recovery of function after TBI.
PMID- 27614010
TI - The peptidomimetic Lau-(Lys-betaNSpe)6-NH2 antagonizes formyl peptide receptor 2
expressed in mouse neutrophils.
AB - The formyl peptide receptor (FPR) gene family has a complex evolutionary history
and comprises eight murine members but only three human representatives. To
enable translation of results obtained in mouse models of human diseases, more
comprehensive knowledge of the pharmacological similarities/differences between
the human and murine FPR family members is required. Compared to FPR1 and FPR2
expressed by human neutrophils, very little is known about agonist/antagonist
recognition patterns for their murine orthologues, but now we have identified two
potent and selective formylated peptide agonists (fMIFL and PSMalpha2) for Fpr1
and Fpr2, respectively. These peptides were used to determine the inhibition
profile of a set of antagonists with known specificities for the two FPRs in
relation to the corresponding murine receptors. Some of the most potent and
selective antagonists for the human receptors proved to be devoid of effect on
their murine orthologues as determined by their inability to inhibit superoxide
release from murine neutrophils upon stimulation with receptor-specific agonists.
The Boc-FLFLF peptide was found to be a selective antagonist for Fpr1, whereas
the lipidated peptidomimetic Lau-(Lys-betaNSpe)6-NH2 and the hexapeptide WRW4
were identified as Fpr2-selective antagonists.
PMID- 27614009
TI - Dabigatran etexilate activation is affected by the CES1 genetic polymorphism
G143E (rs71647871) and gender.
AB - The oral anticoagulant prodrug dabigatran etexilate (DABE) is sequentially
metabolized by intestinal carboxylesterase 2 (CES2) and hepatic carboxylesterase
1 (CES1) to form its active metabolite dabigatran (DAB). A recent genome-wide
association study reported that the CES1 single nucleotide polymorphisms (SNPs)
rs2244613 and rs8192935 were associated with lower DAB plasma concentrations in
the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) study
participants. In addition, gender differences in exposure to DAB were observed in
clinical studies. The aim of this study was to examine the effect of CES1 genetic
polymorphisms and gender on DABE activation using several in vitro approaches.
The genotypes of the CES1 SNPs rs2244613, rs8192935, and the known loss-of
function CES1 variant rs71647871 (G143E), and the activation of DABE and its
intermediate metabolites M1 and M2 were determined in 104 normal human liver
samples. DABE, M1, and M2 activations were found to be impaired in human livers
carrying the G143E variant. However, neither rs2244613 nor rs8192935 was
associated with the activation in human livers. The incubation study of DABE with
supernatant fractions (S9) prepared from the G143E-transfected cells showed that
the G143E is a loss-of-function variant for DABE metabolism. Moreover, hepatic
CES1 activity on M2 activation was significantly higher in female liver samples
than male. Our data suggest that CES1 genetic variants and gender are important
contributing factors to variability in DABE activation in humans. A personalized
DABE treatment approach based on patient-specific CES1 genotypes and sex may have
the potential to improve the efficacy and safety of DABE pharmacotherapy.
PMID- 27614011
TI - The investigational Cystic Fibrosis drug Trimethylangelicin directly modulates
CFTR by stabilizing the first membrane-spanning domain.
AB - Cystic Fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR) gene. The most common mutation, deletion of
phenylalanine 508 (F508del), disrupts tertiary assembly, causing protein
misprocessing and loss of CFTR function in epithelial tissues. Lumacaftor (VX
809) is a Class 1 corrector molecule shown to partially rescue misprocessing of
F508del and together with the potentiator of channel activity: ivacaftor (VX-770)
has been approved for treatment of CF patients homozygous for the F508del
mutation. The specificity of these modulators for CFTR is thought to be conferred
through direct binding. Trimethylangelicin (TMA) is a distinct small molecule
modulator, previously shown to exhibit both corrector and potentiator activities.
We were prompted to determine if TMA also mediates these activities by direct
binding. Interestingly, we found that like VX-770, TMA was effective in enhancing
anion efflux mediated by purified WT-CFTR reconstituted in phospholipid
liposomes. Furthermore, like VX-809, TMA was effective in stabilizing the
functional expression of CFTR lacking the regulatory "R" domain or second
nucleotide-binding domain (NBD2). The smallest domain that was stabilized by TMA
binding was the first membrane-spanning domain (MSD1) as previously observed for
VX-809. Together, our findings support the claim that TMA binds directly to CFTR,
and despite its distinct chemical structure, shares similar mechanisms as VX-770
and VX-809 to potentiate and stabilize CFTR, respectively.
PMID- 27614012
TI - MnO2 nanosheet-assisted ligand-DNA interaction-based fluorescence polarization
biosensor for the detection of Ag+ ions.
AB - Silver (Ag+) ions are highly toxic to aquatic organisms and accumulate in the
human body via the food chain. Therefore, the development of sensitive and
selective quantitative analytical methods for detecting trace amounts of these
ions is necessary. In the present study, a MnO2 nanosheet-assisted, ligand-DNA
interaction and fluorescence polarization-based method was developed, for the
first time, for sensitive detection of Ag+. The addition of Ag+ to the preformed
proflavine-DNA complex induced the release of proflavine, which elicited weak
changes in fluorescence polarization. The subsequent addition of MnO2 nanosheets
magnified the observed changes, making this a feasible method for the detection
of Ag+. The calibration graphs indicated good linearity over the concentration
ranges of 30-240nM for Ag+, with a detection limit (S/N=3) of 9.1nM. This method
additionally exhibits high selectivity. The mechanism underlying the changes in
fluorescence polarization caused by the addition of Ag+ in the presence of MnO2
nanosheets was further explored in this study. These findings demonstrate that
the present MnO2 nanosheet-assisted fluorescence polarization biosensor may
represent a promising tool for the detection of Ag+ ions. The results for
practical detecting Ag+ proved that this biosensor can be applied to
environmental water sample analysis.
PMID- 27614013
TI - Intraventricular administration of urokinase as a novel therapeutic approach for
communicating hydrocephalus.
AB - Fibrosis of the subarachnoid space (SAS) after infection, inflammation, or
hemorrhage can impair cerebrospinal fluid absorption and circulation, causing
diffuse ventricular dilatation. In the present study, we tested the hypothesis
that urokinase (also known as urokinase-type plasminogen activator [uPA]), a
fibrinolytic agent, attenuates fibrosis and ventriculomegaly in a rat model of
kaolin-induced communicating hydrocephalus and thus may have potential as a
therapy for these conditions. Thirty microliters of sterile 25% kaolin suspension
was injected into the basal cisterns of adult Sprague-Dawley rats to induce
hydrocephalus, and 2 intraventricular injections of either uPA or vehicle
(saline) were administered immediately and 3 days thereafter. Ventricular volumes
were measured by magnetic resonance imaging (MRI) on days 3, 14, and 28 after
kaolin injection. Fibrosis and reactive astrogliosis were evaluated on day 28 by
immunofluorescence and Western blotting. Neurocognitive features were tested
using the Morris water maze from days 23 to 28. MRI analysis demonstrated that
kaolin administration successfully induced hydrocephalus in rats and that uPA
treatment significantly attenuated ventricular enlargement. In addition, uPA
inhibited the deposition of laminin and fibronectin, extracellular matrix
molecules, in the SAS, attenuated gliosis, and improved learning and memory in
kaolin-treated rats. Therefore, we concluded that uPA prevents the development of
kaolin-induced communicating hydrocephalus by preventing the development of
subarachnoid fibrosis and by eliciting improvements in neurocognition. The
results of this study indicate that uPA may be a novel clinical therapy for
communicating hydrocephalus.
PMID- 27614014
TI - Work characteristics and psychological symptoms among GPs and community nurses: a
preliminary investigation in China.
AB - Objective: To determine the effect of work characteristics on the psychological
symptoms of general practitioners' (GPs) and community nurses. Design, setting
and participants: A stratified sampling cross-sectional survey was performed at
the 12 community health services centres involved 233 GPs and 202 community
nurses in three cities of Hubei Province in central China. The independent
variables were career prospects, superior recognition, salary fairness,
professional-patient relationship and self-perceived workload. The dependent
variables were the General Health Questionnaire. Results: The generalized linear
regression showed the career prospects had a significant association with GPs'
psychological health, whereas career prospects, self-perceived workload and
superior recognition had significant association on the psychological health of
community nurses. However, salary fairness and professional-patient relationship
were not statistically significant for GPs or community nurses. Conclusions: A
better understanding of the effects of career prospects on the psychological
health of GPs and community nurses, and improvements in superior recognition and
workload on the psychological health of community nurses, would improve
psychological symptoms of primary-level medical staff.
PMID- 27614015
TI - Providing antenatal corticosteroids for preterm birth: a quality improvement
initiative in Cambodia and the Philippines.
AB - Objective: To determine whether a simple quality improvement initiative
consisting of a technical update and regular audit and feedback sessions will
result in increased use of antenatal corticosteroids among pregnant women at risk
of imminent preterm birth delivering at health facilities in the Philippines and
Cambodia. Design: Non-randomized, observational study using a pre-/post
intervention design conducted between October 2013 and June 2014. Setting: A
total of 12 high volume facilities providing Emergency Obstetric and Newborn Care
services in Cambodia (6) and Philippines (6). Intervention: A technical update on
preterm birth and use of antenatal corticosteroids, followed by monthly audit and
feedback sessions. Main Outcome Measure: The proportion of women at risk of
imminent preterm birth who received at least one dose of dexamethasone. Results:
Coverage of at least one dose of dexamethasone increased from 35% at baseline to
86% at endline in Cambodia (P < 0.0001) and from 34% at baseline to 56% at
endline in the Philippines (P < 0.0001), among women who had births at 24-36
weeks. In both settings baseline coverage and magnitude of improvement varied
notably by facility. Availability of dexamethasone, knowledge of use and cost
were not major barriers to coverage. Conclusions: A simple quality improvement
strategy was feasible and effective in increasing use of dexamethasone in the
management of preterm birth in 12 hospitals in Cambodia and Philippines.
PMID- 27614016
TI - Targeting the Worst Symptom in Acute Heart Failure: A Tailored Approach.
PMID- 27614017
TI - Combinational losses of synucleins reveal their differential requirements for
compensating age-dependent alterations in motor behavior and dopamine metabolism.
AB - Synucleins are involved in multiple steps of the neurotransmitter turnover, but
the largely normal synaptic function in young adult animals completely lacking
synucleins suggests their roles are dispensable for execution of these processes.
Instead, they may be utilized for boosting the efficiency of certain molecular
mechanisms in presynaptic terminals, with a deficiency of synuclein proteins
sensitizing to or exacerbating synaptic malfunction caused by accumulation of
mild alterations, which are commonly associated with aging. Although functional
redundancy within the family has been reported, it is unclear whether the
remaining synucleins can fully compensate for the deficiency of a lost family
member or whether some functions are specific for a particular member. We
assessed several structural and functional characteristics of the nigrostriatal
system of mice lacking members of the synuclein family in every possible
combination and demonstrated that stabilization of the striatal dopamine level
depends on the presence of alpha-synuclein and cannot be compensated by other
family members, whereas beta-synuclein is required for efficient maintenance of
animal's balance and coordination in old age.
PMID- 27614018
TI - FoxP3 gene promoter polymorphism affects susceptibility to preeclampsia.
AB - BACKGROUND: Preeclampsia (PE) is a multifactorial pregnancy disorder and is a
major cause of maternal morbidity and mortality. Despite intense study, the
pathophysiology of preeclampsia remains enigmatic. Recent studies have reported
that regulatory T cells (Tregs) is linked with PE. It is well identified that
FoxP3/Scurfin is involved in development and function of Tregs. However, the
association between PE and the FoxP3 gene polymorphism has not been sufficiently
investigated. In this study, we hypothesized that polymorphisms of the FoxP3 may
be related to PE. METHODS: We assessed the relationship between four single
nucleotide polymorphisms (SNPs) in the FoxP3 genes with sequence-specific primers
(PCR-SSP) in 81 PE patients and 90 age-matched controls. RESULT: We identified
significant difference of rs4824747 GG genotype frequency between the PE and
control groups. Women with GG genotypes exhibited higher (OR=6.25, 95% CI=2.63
14.85; P<0.0001) risk of developing PE. None of the other investigated SNPs
(rs2232365, rs3761547 and rs3761548) showed significant association with PE.
CONCLUSION: We suggest that FoxP3 polymorphisms (rs4824747) could be a potential
contributor for the development of PE in Iranian women.
PMID- 27614019
TI - DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase
Syk.
AB - The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a
proline or alanine in second position. Although linked to several pathways
including cell survival and metabolism, the molecular mechanisms underlying these
outcomes are poorly understood. We identified a novel interaction of DPP9 with
Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk
signalling can be terminated by degradation, requiring the ubiquitin E3 ligase
Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in
position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1
strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl
interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk
ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating
Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of
Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule
pathway.
PMID- 27614021
TI - A mathematical model of endothelial nitric oxide synthase activation with time
delay exhibiting Hopf bifurcation and oscillations.
AB - Nitric oxide (NO) is a gaseous compound that serves as a signaling molecule in
cellular interactions. In the vasculature, NO is synthesized from endogenous
agents by endothelial nitric oxide synthase (eNOS) where it plays key roles in
several functions related to homeostasis, adaptation, and development. Recent
experimental studies have revealed cycles of increasing and decreasing NO
production when eNOS is stimulated by factors such as glucose or insulin. We
offer a mathematical model of a generic amino acid receptor site on eNOS wherein
this species is subject to activation/deactivation by a pair of interactive
kinase and phosphatase species. The enzyme kinetic model is presented as a system
of ordinary differential equations including time delay to allow for various
intermediate, unspecified complexes. We show that under conditions on the model
parameters, varying the delay time may give rise to a Hopf bifurcation.
Properties of the bifurcating solutions are explored via a center manifold
reduction, and a numerical illustration is provided.
PMID- 27614022
TI - The metabolic sensor Sirt1 and the hypothalamus: Interplay between peptide
hormones and pro-hormone convertases.
AB - The last decade had witnessed a tremendous progress in our understanding of the
causes of metabolic diseases including obesity. Among the contributing factors
regulating energy balance are nutrient sensors such as sirtuins. Sirtuin1
(Sirt1), a NAD + - dependent deacetylase is affected by diet, environmental
stress, and also plays a critical role in metabolic health by deacetylating
proteins in many tissues, including liver, muscle, adipose tissue, heart,
endothelium, and in the complexity of the hypothalamus. Because of its dependence
on NAD+, Sirt1 also functions as a nutrient/redox sensor, and new novel data show
a function of this enzyme in the maturation of hypothalamic peptide hormones
controlling energy balance either through regulation of specific nuclear
transcription factors or by regulating specific pro-hormone convertases (PCs)
involved in the post-translational processing of pro-hormones. The post
translational processing mechanism of pro-hormones is critical in the
pathogenesis of obesity as recently shown that metabolic and physiological
triggers affect the biosynthesis and processing of many peptides hormones.
Specific regulation of pro-hormone processing is likely another key step where
final amounts of bioactive peptides can be tightly regulated. Different factors
stimulate or inhibit pro-hormones biosynthesis in concert with an increase in the
PCs involved in the maturation of bioactive hormones. Adding more complexity to
the system, the new studies describe here suggest that Sirt1 could also regulate
the fate of peptide hormone biosynthesis. The present review summarizes the
recent progress in hypothalamic SIRT1 research with a particular emphasis on the
tissue-specific control of neuropeptide hormone maturation. The series of studies
done in mouse and rat models strongly advocate for the first time that a
deacetylating enzyme could be a regulator in the maturation of peptide hormones
and their processing enzymes. These discoveries are the culmination of the first
in-depth understanding of the metabolic role of Sirt1 in the brain. It suggests
that Sirt1 behaves differently in the brain than in organs such as the liver and
pancreas, where the enzyme has been more commonly studied.
PMID- 27614023
TI - Protein tyrosine phosphatase SHP-1 modulates osteoblast differentiation through
direct association with and dephosphorylation of GSK3beta.
AB - SHP-1, the Src homology-2 (SH2) domain-containing phosphatase 1, is a cytosolic
protein-tyrosine phosphatase (PTP) predominantly expressed in hematopoietic
derived cells. Previous studies have focused on the involvement of SHP-1 in
osteoclastogenesis. Using primary cultured mouse fetal calvaria-derived
osteoblasts as a model, this study aims to investigate the effects of SHP-1 on
differentiation and mineralization of osteoblasts and elucidate the signaling
pathways responsible for these effects. We found that osteoblasts treated by
osteogenic media showed significant increase in SHP-1 expression, which
contributed to osteoblastic differentiation and mineralization. Using
immunoprecipitation assay, we found that a direct association between SHP-1 and
glycogen synthase kinase (GSK)-3beta could be detected in differentiated
osteoblasts and was significantly inhibited by SHP-1 inhibitor NSC87877.
Inhibition of SHP-1 activated GSK3beta, thereby leading to suppression of
osteoblast differentiation and mineralization, which could be rescued by the
inhibitor of GSK3beta. In addition, we found that rosiglitazone (RSG) treatment
led to significant decrease in SHP-1 expression. Overexpression of SHP-1 reversed
RSG-induced GSK3beta activation, thus rescuing the inhibitory effect of RSG on
osteoblast differentiation and mineralization. These findings suggest that
protein tyrosine phosphatase SHP-1 may act as a positive regulator of osteoblast
differentiation through direct association with and dephosphorylation of
GSK3beta. Downregulation of SHP-1 may contribute to RSG-induced inhibition of
mouse calvaria osteoblast differentiation by activating GSK3beta-dependent
pathway.
PMID- 27614024
TI - Physiological variability and atrial fibrillation therapy: Insights from
population-based mathematical modeling.
PMID- 27614020
TI - Transcriptional rewiring over evolutionary timescales changes quantitative and
qualitative properties of gene expression.
AB - Evolutionary changes in transcription networks are an important source of
diversity across species, yet the quantitative consequences of network evolution
have rarely been studied. Here we consider the transcriptional 'rewiring' of the
three GAL genes that encode the enzymes needed for cells to convert galactose to
glucose. In Saccharomyces cerevisiae, the transcriptional regulator Gal4 binds
and activates these genes. In the human pathogen Candida albicans (which last
shared a common ancestor with S. cerevisiae some 300 million years ago), we show
that different regulators, Rtg1 and Rtg3, activate the three GAL genes. Using
single-cell dynamics and RNA-sequencing, we demonstrate that although the overall
logic of regulation is the same in both species-the GAL genes are induced by
galactose-there are major differences in both the quantitative response of these
genes to galactose and in the position of these genes in the overall
transcription network structure of the two species.
PMID- 27614025
TI - Economic analysis of remote monitoring of cardiac implantable electronic devices:
Results of the Health Economics Evaluation Registry for Remote Follow-up (TARIFF)
study.
AB - BACKGROUND: Remote monitoring (RM) of cardiac implantable electronic devices has
been demonstrated to improve outpatient clinic workflow and patient management.
However, few data are available on the socioeconomic impact of RM. OBJECTIVE: The
aim of this study was to assess the costs and benefits of RM compared with
standard care (SC). METHODS: We used 12-month patient data from the Health
Economics Evaluation Registry for Remote Follow-up (TARIFF) study (N = 209; RM: n
= 102 (48.81%); SC: n = 107 (51.19%)). Cost comparison was made from 2
perspectives: the health care system (HCS) and patients. The use of health care
resources was defined on the basis of hospital clinical folders. Out-of-pocket
expenses were reported directly by patients. RESULTS: HCS perspective: The
overall mean annual cost per patient in the SC group (?1044.89 +/- ?1990.47) was
significantly higher than in the RM group (?482.87 +/- ?2488.10) (P < .0001),
with a reduction of 53.87% being achieved in the RM group. The primary driver of
cost reduction was the cost of cardiovascular hospitalizations (SC: ?'886.67 +/-
?1979.13 vs RM: ?432.34 +/- ?2488.10; P = .0030). Patient and caregiver
perspective: The annual cost incurred by patients was significantly higher in the
SC group than in the RM group (SC: ?169.49 +/- ?189.50 vs RM: ?56.87 +/- ?80.22;
P < .0001). Patients' quality-adjusted life-years were not significantly
different between the groups. Provider perspective: The total number of
inhospital device follow-up visits was reduced by 58.78% in the RM group.
CONCLUSION: RM of patients with cardiac implantable electronic devices (CIEDs) is
cost saving from the perspectives of the HCS, patients, and caregivers.
Introducing appropriate reimbursements will make RM sustainable even for the
provider, i.e. the hospitals which provide the service and encourage widespread
adoption of RM.
PMID- 27614026
TI - Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in
Asian patients with atrial fibrillation: A meta-analysis of contemporary
randomized controlled trials.
AB - BACKGROUND: Although randomized controlled trials (RCTs) indicated that standard
dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling,
low dose NOACs are commonly used in clinical practice in Asia. OBJECTIVE: The
purpose of this study was to assess the relative therapeutic benefit and risk of
standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs.
METHODS: We performed a prespecified meta-analysis of 3155 Asian patients with
NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy)
and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation
in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy
and safety with standard dose vs low dose NOACs were compared by risk ratios
(RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence
network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and
ARISTOTLE was constructed with the Bayesian method. RESULTS: Risks of stroke or
systemic embolism and ischemic stroke were significantly reduced with standard
dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79,
respectively). Rates of major, intracranial, and life-threatening bleeding with 2
dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI
0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all
cause mortality and the net clinical outcome with standard dose NOACs were lower
but not statistically significant (absolute reduction 0.4% per year and 1.1% per
year, respectively). Network meta-analyses demonstrated that standard dose NOACs
had the most favorable risk-benefit profile among oral anticoagulants.
CONCLUSION: In Asian patients, standard dose NOACs represent a more appealing
therapeutic option than low dose NOACs, with a significant reduction in ischemic
stroke without an excess of major bleeding.
PMID- 27614027
TI - Totally endoscopic robotic epicardial ablation of refractory left ventricular
summit arrhythmia: First-in-man.
PMID- 27614028
TI - 'The one with the purse makes policy': Power, problem definition, framing and
maternal health policies and programmes evolution in national level
institutionalised policy making processes in Ghana.
AB - This paper seeks to advance our understanding of health policy agenda setting and
formulation processes in a lower middle income country, Ghana, by exploring how
and why maternal health policies and programmes appeared and evolved on the
health sector programme of work agenda between 2002 and 2012. We theorized that
the appearance of a policy or programme on the agenda and its fate within the
programme of work is predominately influenced by how national level decision
makers use their sources of power to define maternal health problems and frame
their policy narratives. National level decision makers used their power sources
as negotiation tools to frame maternal health issues and design maternal health
policies and programmes within the framework of the national health sector
programme of work. The power sources identified included legal and structural
authority; access to authority by way of political influence; control over and
access to resources (mainly financial); access to evidence in the form of health
sector performance reviews and demographic health surveys; and knowledge of
national plans such as Ghana Poverty Reduction Strategy. Understanding of power
sources and their use as negotiation tools in policy development should not be
ignored in the pursuit of transformative change and sustained improvement in
health systems in low- and middle income countries (LMIC).
PMID- 27614030
TI - The benefit of silicone stents in primary endonasal dacryocystorhinostomy: a
systematic review and meta-analysis.
AB - OBJECTIVE: To critically evaluate the evidence comparing success rates of
endonasal dacryocystorhinostomy (EN-DCR) with and without silicone tubing and to
thus determine whether silicone intubation is beneficial in primary EN-DCR.
DESIGN: Systematic review and meta-analysis. SEARCH STRATEGY: A literature search
was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH
BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders groups trials
register using a combination of various MeSH. The date of last search was January
2016. This review was limited to randomised controlled trials (RCTs) in English
language. Risk of bias was assessed using the Cochrane Collaboration's risk of
bias tool. Chi-square and I2 statistics were calculated to determine the presence
and extent of statistical heterogeneity. EVALUATION METHOD: Study selection, data
extraction and risk of bias scoring were performed independently by two authors
in concordance with the PRISMA statement. RESULTS: Five RCTs (447 primary EN-DCR
procedures in 426 patients) were included for analysis. Moderate interstudy
statistical heterogeneity was demonstrated (Chi2 = 6.18; d.f. = 4; I2 = 35%).
Bicanalicular silicone stents were used in 229 and not used in 218 procedures.
The overall success rate of EN-DCR was 92.8% (415/447). The success rate of EN
DCR was 93.4% (214/229) with silicone tubing and 92.2% (201/218) without silicone
tubing. Meta-analysis using a random-effects model showed no statistically
significant difference in outcomes between the two groups (P = 0.63; RR = 0.79;
95% CI = 0.3-2.06). CONCLUSIONS: Our review and meta-analysis did not demonstrate
an additional advantage of silicone stenting. A high-quality well-powered
prospective multicentre RCT is needed to further clarify on the benefit of
silicone stents.
PMID- 27614029
TI - Contribution of mast cells to injury mechanisms in a mouse model of pediatric
traumatic brain injury.
AB - The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to
the immature brain are more severe and persistent than injuries to the adult
brain. Understanding this developmental sensitivity is critical because children
under 4 years of age of sustain TBI more frequently than any other age group. One
of the first events after TBI is the infiltration and degranulation of mast cells
(MCs) in the brain, releasing a range of immunomodulatory substances; inhibition
of these cells is neuroprotective in other types of neonatal brain injury. This
study investigates for the first time the role of MCs in mediating injury in a P7
mouse model of pediatric contusion-induced TBI. We show that various neural cell
types express histamine receptors and that histamine exacerbates excitotoxic cell
death in primary cultured neurons. Cromoglycate, an inhibitor of MC
degranulation, altered the inflammatory phenotype of microglia activated by TBI,
reversing several changes but accentuating others, when administered before TBI.
However, without regard to the time of cromoglycate administration, inhibiting MC
degranulation did not affect cell loss, as evaluated by ventricular dilatation or
cleaved caspase-3 labeling, or the density of activated microglia, neurons, or
myelin. In double-heterozygous cKit mutant mice lacking MCs, this overall lack of
effect was confirmed. These results suggest that the role of MCs in this model of
pediatric TBI is restricted to subtle effects and that they are unlikely to be
viable neurotherapeutic targets. (c) 2016 Wiley Periodicals, Inc.
PMID- 27614031
TI - Late isolated ocular toxoplasmosis in a belatacept-treated kidney transplant
patient.
PMID- 27614032
TI - Beyond the learning curve: length of global health electives.
PMID- 27614034
TI - Environmental behavior of the chiral insecticide fipronil: Enantioselective
toxicity, distribution and transformation in aquatic ecosystem.
AB - The enantioselective environmental behaviors of the chiral insecticide fipronil
and its metabolites in lab-scale aquatic ecosystems were studied and the toxicity
of fipronil enantiomers and the metabolites to non-target organisms Lemna minor
(L. minor) and Anodonta woodiana (A. woodiana) was also investigated in this
work. Water-sediment, water-L. minor, water-A. woodiana, and water-sediment-L.
minor-A. woodiana ecosystems were set up and exposed to fipronil through a 90-day
period. The results showed fipronil could be degraded significantly faster (half
life of 4.6 days) in the complex water-sediment-L. minor-A. woodiana ecosystem.
A. woodiana played a crucial role in the dissipation of fipronil, and the
microorganisms in the sediment also made great contribution to the degradation of
fipronil in aquatic ecosystems. All the three metabolites fipronil desulfinyl,
fipronil sulfide and fipronil sulfone were detected in the ecosystems and were
more persistent than fipronil. Enantioselective degradation of fipronil was
observed with S-fipronil being preferentially degraded in sediment and L. minor,
while R-fipronil was metabolized preferentially in A. woodiana. EC50 for L. minor
was obtained using 7-day exposure, and for A. woodiana was obtained using 72-h
exposure. S-fipronil was more toxic to A. woodiana, while R-fipronil showed
higher toxicity to L. minor. Moreover, the three metabolites were found more
toxic than fipronil indicating significant environment risks due to their
persistence. The present study might have important implications for the risk
assessment of fipronil and its metabolites in real aquatic environment.
PMID- 27614033
TI - Interaction between the plant ApDef1 defensin and Saccharomyces cerevisiae
results in yeast death through a cell cycle- and caspase-dependent process
occurring via uncontrolled oxidative stress.
AB - BACKGROUND: Plant defensins were discovered at beginning of the 90s'; however,
their precise mechanism of action is still unknown. Herein, we studied ApDef1
Saccharomyces cerevisiae interaction. METHODS: ApDef1-S. cerevisiae interaction
was studied by determining the MIC, viability and death kinetic assays. Viability
assay was repeated with hydroxyurea synchronized-yeast and pretreated with CCCP.
Plasma membrane permeabilization, ROS induction, chromatin condensation, and
caspase activation analyses were assessed through Sytox green, DAB, DAPI and FITC
VAD-FMK, respectively. Viability assay was done in presence of ascorbic acid and
Z-VAD-FMK. Ultrastructural analysis was done by electron microscopy. RESULTS:
ApDef1 caused S. cerevisiae cell death and MIC was 7.8MUM. Whole cell population
died after 18h of ApDef1 interaction. After 3h, 98.76% of synchronized cell
population died. Pretreatment with CCCP protected yeast from ApDef1 induced
death. ApDef1-S. cerevisiae interaction resulted in membrane permeabilization,
H2O2 increased production, chromatin condensation and caspase activation.
Ascorbic acid prevented yeast cell death and membrane permeabilization. Z-VAD-FMK
prevented yeast cell death. CONCLUSIONS: ApDef1-S. cerevisiae interaction caused
cell death through cell cycle dependentprocess which requires preserved membrane
potential. After interaction, yeast went through uncontrolled ROS production and
accumulation, which led to plasma membrane permeabilization, chromatin
condensation and, ultimately, cell death by activation of caspase-dependent
apoptosis via. GENERAL SIGNIFICANCE: We show novel requirements for the
interaction between plant defensin and fungi cells, i.e. cell cycle phase and
membrane potential, and we indicate that membrane permeabilization is probably
caused by ROS and therefore, it would be an indirect event of the ApDef1-S.
cerevisiae interaction.
PMID- 27614035
TI - Denitrifying bioreactor clogging potential during wastewater treatment.
AB - Chemoheterotrophic denitrification technologies using woodchips as a solid carbon
source (i.e., woodchip bioreactors) have been widely trialed for treatment of
diffuse-source agricultural nitrogen pollution. There is growing interest in the
use of this simple, relatively low-cost biological wastewater treatment option in
waters with relatively higher total suspended solids (TSS) and chemical oxygen
demand (COD) such as aquaculture wastewater. This work: (1) evaluated hydraulic
retention time (HRT) impacts on COD/TSS removal, and (2) assessed the potential
for woodchip clogging under this wastewater chemistry. Four pilot-scale woodchip
denitrification bioreactors operated for 267 d showed excellent TSS removal
(>90%) which occurred primarily near the inlet, and that COD removal was
maximized at lower HRTs (e.g., 56% removal efficiency and 25 g of COD removed per
m3 of bioreactor per d at a 24 h HRT). However, influent wastewater took
progressively longer to move into the woodchips likely due to a combination of
(1) woodchip settling, (2) clogging due to removed wastewater solids and/or
accumulated bacterial growth, and (3) the pulsed flow system pushing the chips
away from the inlet. The bioreactor that received the highest loading rate
experienced the most altered hydraulics. Statistically significant increases in
woodchip P content over time in woodchip bags placed near the bioreactor outlets
(0.03 vs 0.10%P2O5) and along the bioreactor floor (0.04 vs. 0.12%P2O5) confirmed
wastewater solids were being removed and may pose a concern for subsequent
nutrient mineralization and release. Nevertheless, the excellent nitrate-nitrogen
and TSS removal along with notable COD removal indicated woodchip bioreactors are
a viable water treatment technology for these types of wastewaters given they are
used downstream of a filtration device.
PMID- 27614036
TI - Detailed comparison of bacterial communities during seasonal sludge bulking in a
municipal wastewater treatment plant.
AB - In this study, pyrosequencing combined with clone library analysis, qPCR, and
fluorescent in situ hybridization (FISH) were performed to identify detailed
changes of bacterial and filamentous bacterial communities in activated sludge
(AS) in 3 types of typical AS samples: sludge bulking (B-AS), excessive bulking
(EB-AS), and non-bulking (N-AS). Sludge bulking resulted in a decrease in total
bacterial numbers from (6.4 +/- 0.18) * 108 gene copies/mL in N-AS to (2.4 +/-
0.22) * 108 in EB-AS and a decrease in bacterial diversity from 2757 OTUs in N-AS
to 2217 OTUs in EB-AS. With the occurrence of sludge bulking, Actinobacteria and
Firmicutes increased sharply, whereas Proteobacteria, which was the predominant
phylum in N-AS, decreased markedly. In addition, Nitrospirae, a major lineage of
the nitrite-oxidizing bacteria, had quite a low abundance in EB-AS (0.15%), while
it was relatively high in N-AS (1.17%). On the other hand, filamentous bacteria
accounted for 28.77% and 5.72% of total sequences in EB-AS and N-AS,
respectively. More interestingly, 11 types of filamentous bacteria were always
present in 3 types of typical AS samples from different stages of sludge bulking,
and most of them enriched in EB-AS compared to N-AS. It is noteworthy that, in
addition to the frequently reported filamentous bacteria such as Candidatus M.
parvicella and Tetrasphaera, novel filamentous species of Trichococcus might
exist in this bulking WWTP. Our results reveal that sludge bulking are derived
from diverse taxa, which expands previous understanding and provides new insight
into the underlying complications of the bulking phenomenon in AS.
PMID- 27614037
TI - Effects of UV-based treatment on volatile disinfection byproducts in a
chlorinated, indoor swimming pool.
AB - Ultraviolet (UV) irradiation and chlorination are commonly used together in
treatment of swimming pool water because they function as complementary
disinfectants and because UV-based processes have been shown to promote
photodecay of chloramines. However, UV-based treatment also has the potential to
promote formation of some disinfection byproducts (DBPs). As a result, the
overall effects of UV irradiation with chlorination on swimming pool chemistry
remain unclear. To address this issue, a three-year study was conducted in a
chlorinated, indoor swimming pool under three different operating conditions:
conventional chlorination (1st year) which served as a control, chlorination
augmented by MP UV irradiation (2nd year), and chlorination augmented by LP UV
irradiation (3rd year). Water samples were collected from the pool for
measurement of pH, temperature, total alkalinity, free and combined chlorine,
eleven volatile DBPs, and urea concentration. After installation of MP UV, the
concentrations of most volatile DBPs decreased; similar effects were observed
after inclusion of LP UV. Collectively, these results imply an overall
improvement in water quality as a result of the inclusion of the both UV systems.
In general, MP UV was more efficient than LP UV for reducing the concentrations
of most of the volatile DBPs measured in this pool. However, a need exists to
standardize the application of UV systems in recreational water settings.
PMID- 27614038
TI - Glutathione-mediated reversal of streptomycin susceptibility is refractory to the
status of glutathione-S-transferase (gst) or translational fidelity of
Escherichia coli.
PMID- 27614039
TI - Chemical characterization of simulated landfill soil leachates from Nigeria and
India and their cytotoxicity and DNA damage inductions on three human cell lines.
AB - Landfill soils are sources of emerging carcinogens, teratogens and mutagens in
the environment. There is inadequate information on its possible health risk and
cytogenotoxicity. This study evaluated chemical characterization of four
simulated landfill leachates with their cytotoxicity and DNA damage in human
cells. Hepatocarcinoma (HepG2), lymphoma (Jurkat) and osteosarcoma (HOS) cells,
incubated with 6.25, 12.5, 25, 50, 75 and 100% of Aba Eku (AEL), Olusosun (OSL),
Awotan (AWL) and Nagpur (NPL) simulated leachates for 24 h, were assessed for
cell viability using MTT assay and morphological alterations. DNA damage was also
assessed after 24 h treatment of cells with sub-lethal concentrations of the
leachates using comet assay. Metals and organic compounds in the soil leachates
were determined using inductively coupled plasma-mass spectrometry (ICP-MS) and
gas chromatography-mass spectroscopy (GC-MS) respectively. The leachates induced
significant cytotoxicity in the treated cells with evidence of apoptosis;
shrunken morphologies, detachment from the substratum and cytoplasmic
vacuolations. Similarly, there was significant DNA damage induced in the treated
cells, with increased Olive tail moment, tail length and % tail DNA. Jurkat was
the most sensitive (Jurkat > HepG2 > HOS) to the cytotoxic and genotoxic effects
of the leachates. All the analyzed metals except Cd, Fe, Zn and Mn were found at
levels lower than standard allowable limits. 32, 17, 23 and 23 different PAHs and
PCBs were detected in AEL, AWL, OSL and NPL respectively, at varying retention
peak times. These toxic constituents induced the observed cytogenotoxicity in the
cells and may suggest possible public health risk.
PMID- 27614040
TI - Assessment of organochlorine pesticide residues in raw food samples from open
markets in two African cities.
AB - This study investigates the level of organochlorine pesticides in the raw food
from open markets in Kinshasa, Democratic Republic of Congo (DRC), and
Johannesburg, South Africa. It assesses the potential health risks associated
with the organochlorine pesticide residues. The Quick, Easy, Cheap, Effective,
Rugged, and Safe (QuEChERS) method has been developed for sample preparation. A
total of 120 food samples (beans, cabbage, beef, and fish) were obtained from the
open markets. The mean concentrations of organochlorine pesticides in raw foods
collected from the Johannesburg market were significantly higher (p < 0.05) than
those from the Kinshasa market. DDE recorded the highest mean concentration
(253.58 +/- 4.78 MUg kg-1) in beef from Johannesburg, and alpha-BHC recorded the
lowest mean concentration (38.54 +/- 7.46 MUg kg-1) in beans from Kinshasa. The
investigation of health risk estimates revealed that the number of organochlorine
pesticides exceeded the reference dose in the collected food samples.
PMID- 27614041
TI - Scapular asymmetry in participants with and without shoulder impingement
syndrome; a three-dimensional motion analysis.
AB - BACKGROUND: This study analyzed the dynamic three-dimensional scapular kinematics
and scapular asymmetry in participants with and without shoulder impingement
syndrome. METHODS: Twenty-nine participants with shoulder impingement syndrome,
have been suffering from unilateral shoulder pain at the dominant arm lasting
more than six weeks and thirty-seven healthy controls participated in the study.
Scapular kinematics was measured with an electromagnetic tracking device during
shoulder elevation in the sagittal plane. Data for bilateral scapular orientation
were analyzed at 30 degrees , 60 degrees , 90 degrees , and 120 degrees of
humerothoracic elevation and lowering. The symmetry angle was calculated to
quantify scapular asymmetry throughout shoulder elevation. FINDINGS: Statistical
comparisons indicated that the scapula was more downwardly rotated (p<0.001) and
anteriorly tilted (p=0.005) in participants with shoulder impingement syndrome
compared to healthy controls. Side-to-side comparisons revealed that the scapula
was more anteriorly tilted on the involved side of participants with shoulder
impingement syndrome (p=0.01), and the scapula was rotated more internally
(p=0.02) and downwardly (p=0.01) on the dominant side of healthy controls.
Although there were side-to-side differences in both groups, symmetry angle
calculation revealed that the scapular movement was more asymmetrical for
scapular internal and upward rotation in individuals with shoulder impingement
syndrome when compared with healthy controls (p<0.05). INTERPRETATION: The
findings of the study increase our knowledge and understanding of scapular
alterations in symptomatic and asymptomatic populations, which creates
biomechanical considerations for shoulder assessment and rehabilitation.
PMID- 27614042
TI - Phospholipid-protein balance in affective disorders: Analysis of human blood
serum using Raman and FTIR spectroscopy. A pilot study.
AB - Raman and FTIR (Fourier Transform Infra Red) spectroscopies provide information
on the chemical structure of compounds through identification and analysis of
functional groups. In the present study, both spectroscopic techniques were used
for investigating the phospholipid - protein balance in blood serum of depressed
subjects (major depressive disorder and bipolar disorder type I or II) taking
also into account their age and gender. The obtained results were compared with
those of healthy subjects. The Raman and FTIR (using ATR (Attenuated Total
Reflectance) technique), spectra show that a correlation between the level of
phospholipids and proteins exists. Indeed, in depressed subjects the quantity of
phospholipids and proteins is lower, compared to healthy ones. The second
derivative of FTIR spectra shows that phospholipids directly affect the structure
of proteins and their functions. In all male depressed subjects a higher amount
of phospholipids and proteins compared to female depressed subjects was measured,
offering them faster recovery perspectives. Spectroscopy results show that the
phospholipids' and proteins' levels are lower in depressed subjects from 41 to 65
compared to the age group between 20 and 40, independently from the gender.
Consequently, this study shows that Raman and infrared spectroscopies might be
applied as a diagnostic tool to evaluate the balance between phospholipids and
proteins in blood serum as a potential biomarker in depressive disorders.
PMID- 27614044
TI - Refolding of urea denatured cytochrome c: Role of hydrophobic tail of the
cationic gemini surfactants.
AB - The refolding of urea denatured horse heart cytochrome c (h-cyt-c) under the
influence of ester based cationic gemini surfactants [ethane-1, 2-diyl bis(N, N
dimethyl-N-alkylammoniumacetoxy) dichlorides] 16-E2-16, 14-E2-14 and 12-E2-12 (n
E2-n) was performed by using UV-visible, fluorescence and circular dichroism (CD)
spectroscopic techniques. We found that n-E2-n geminis promote the formation of
molten globule (MG) like state upon addition into the urea denatured h-cyt-c. The
comparative study of refolding of denatured h-cyt-c with n-E2-n, cationic gemini
surfactant show stabilization of MG-like state influenced by hydrophobic
interactions. The formation of MG-like state from the unfolded protein confirms
the presence of some regular structures induced by n-E2-n gemini surfactants.
Thermodynamic parameters for refolding of h-cyt-c by n-E2-n were also measured
and the m-values of all the refolded states of h-cyt-c by n-E2-n show marked
difference. The higher m-values correspond to the larger hydrophobic chain length
indicates that refolding ability of the n-E2-n depends on the alkyl chain length.
The result is related to the stronger hydrophobic forces due to the presence of
two head groups and two hydrophobic hydrocarbon tails. This study showed that
these cationic gemini surfactants were efficiently utilized in the protein
refolding studies.
PMID- 27614043
TI - Adsorptive removal of ciprofloxacin by sodium alginate/graphene oxide composite
beads from aqueous solution.
AB - Graphene oxide (GO) was encapsulated into environmentally benign sodium alginate
(SA) to prepare a GO-SA composite hydrogel and an aerogel, which were then used
as adsorbents to remove ciprofloxacin from aqueous solutions. The characteristics
of these materials were investigated using scanning electron microscopy (SEM),
Brunauer-Emmett-Teller (BET) analysis, Fourier transform infrared (FT-IR)
spectroscopy, thermogravimetric analysis (TGA) and X-ray photoelectron
spectroscopy (XPS). The characterizations demonstrated that the incorporation of
GO improved the pore uniformity of the gels and decreased the pore sizes. Kinetic
studies showed that the adsorption capacity of SA composite gels increased
approximately seven to nine times after the incorporation of GO, matching with
pseudo-second-order models. Non-linear fitting parameters of adsorption isotherm
studies indicated that a Langmuir model could precisely represent the adsorption
behavior. GO-SA aerogels exhibited high tolerance to changes in pH and ionic
strength; changes in these parameters minimally influenced the adsorption
capacity of the GO-SA aerogels for ciprofloxacin. This work is especially
relevant for environmental applications. These graphene-based composites are
environmentally benign adsorbents and can remove organic contaminants from
aqueous solutions.
PMID- 27614045
TI - Tuning PbS QDs deposited onto TiO2 nanotube arrays to improve
photoelectrochemical performances.
AB - The ability to anchor quantum dots (QDs) onto the inner channels of nanotube
arrays affords the opportunity to engineer the electron and band structures for a
variety of applications. During the successive ionic layer adsorption and
reaction (SILAR) preparation, the deposition of PbS QDs had been tuned by
adjusting the concentration ratio of sulfur and lead sources onto the TiO2
nanotube array (TNA) support formed via anodic ionization. The
photoelectrochemical properties of the PbS QD sensitized TNAs were optimized. The
sample microstructure and photoelectrochemical properties were analyzed with X
ray diffraction (XRD), transmission electron microscopy (TEM), field-emission
scanning electron microscopy (FE-SEM), UV-visible diffuse reflectance
spectroscopy (UV-vis DRs), photoluminescence (PL), current-voltage
characteristics (J-V), electrochemical impedance spectroscopy (EIS), transient
photovoltage plots and Mott-Schottky curves. The size and distribution of the PbS
QDs were tuned by varying the concentration ratio of sulfur and lead sources
during the SILAR process. The band gap structure, flat band potential, lifetime
and transport of the photo-induced charge carriers were subsequently modified.
With a S/Pb concentration ratio of 5, the samples demonstrated the best
photoelectrochemical characteristics with a peak photocurrent density of 8.24mAcm
2 and a corresponding photoconversion efficiency of 7.80%.
PMID- 27614047
TI - The relationship between sensory latency and amplitude.
AB - PURPOSE: To prove that the relationship between sensory latencies and amplitudes
is useful in determining the severity of neuropathies. This is achieved by
deriving a mathematical relationship between sensory distal latency and
amplitude. Determine whether sensory amplitudes below predicted correlate with a
worse pathology. PROCEDURES: Patients seen for Nerve Conduction Studies by the
Department of Physical Medicine and Rehabilitation at Cooper University Hospital
between 12/1/12 and 12/31/14 were invited to participate in a prospective
database. The median, ulnar and sural sensory latencies and amplitudes were
analyzed with both linear and power regression. Patients with amplitudes above
and below the regression curve were compared for latency, amplitude and velocity
of other nerves. Carpal Tunnel Patients were analyzed to determine whether Median
sensory amplitude below predicted correlated with more severe disease. RESULTS:
For the Median nerve, Power Regression Analysis showed a stronger correlation
(R2=0.54) than linear regression (R2=0.34). Patients with Median sensory
amplitude below the power correlation curve showed significantly longer ulnar
sensory latency, and lower sensory amplitude than those above. Carpal Tunnel
Syndrome patients with Median sensory amplitude well below predicted by the power
relationship showed more advanced disease. For the ulnar and sural sensory nerve,
the difference between power and linear regression was not significant.
CONCLUSIONS: A power regression curve correlates sensory latency and amplitude
better than linear regression. The latency amplitude relationship correlates with
other parameters of nerve function and severity of Carpal Tunnel Syndrome. This
implies that below predicted sensory amplitude may indicate worse disease, and
could be a useful diagnostic tool.
PMID- 27614046
TI - IGF2 Is Up-regulated by Epigenetic Mechanisms in Hepatocellular Carcinomas and Is
an Actionable Oncogene Product in Experimental Models.
AB - BACKGROUND & AIMS: Effective treatments are urgently needed for hepatocellular
carcinoma (HCC), which is usually diagnosed at advanced stages. Signaling via the
insulin-like growth factor (IGF) pathway is aberrantly activated in HCC by IGF2
overexpression. We aimed to elucidate the mechanism of IGF2 overexpression and
its oncogenic activities and evaluate the anti-tumor effects of reducing IGF2
signaling. METHODS: We obtained 228 HCC samples from patients who underwent liver
resection, 168 paired non-tumor adjacent cirrhotic liver samples, and 10 non
tumor liver tissues from patients undergoing resection for hepatic hemangioma. We
analyzed gene expression, microRNA, and DNA methylation profiles for all samples,
focusing on genes in the IGF signaling pathway. IGF2 was expressed in SNU449 and
PLC5 HCC cells and knocked down with small hairpin RNAs in Hep3B and Huh7 cell
lines. We analyzed these cells for proliferation, apoptosis, migration, and
colony formation. We performed studies in mice engineered to express Myc and Akt1
in liver, which develop liver tumors, with or without hepatic expression of Igf2.
Mice with xenograft tumors grown from HCC cells were given a monoclonal antibody
against IGF1 and IGF2 (xentuzumab), along with sorafenib; tumor growth was
measured and tissues were analyzed by immunohistochemistry and immunoblots.
RESULTS: Levels of IGF2 messenger RNA and protein were increased >20-fold in 15%
of human HCC tissues compared with non-tumor liver tissues. Methylation at the
fetal promoters of IGF2 was reduced in the HCC samples and cell lines that
overexpressed IGF2, compared with those that did not overexpress this gene, and
non-tumor tissues. Tumors that overexpressed IGF2 had gene expression patterns
significantly associated with hepatic progenitor cell features, stellate cell
activation, NOTCH signaling, and an aggressive phenotype (P < .0001). In mice
engineered to express Myc and Akt1 in liver, co-expression of Igf2 accelerated
formation of liver tumors, compared to mice with livers expressing only Myc and
Akt1, and shortened survival times (P = .02). The antibody xentuzumab blocked
phosphorylation of IGF1 receptor in HCC cell lines and reduced their
proliferation and colony formation. In mice with xenograft tumors, injection of
xentuzumab, with or without sorafenib, slowed tumor growth and increased survival
times compared to vehicle or sorafenib alone. Xentuzumab inhibited
phosphorylation of IGF1 receptor and AKT and reduced decreased tumor
vascularization compared with vehicle. CONCLUSIONS: A large proportion of HCC
samples were found to overexpress IGF2, via demethylation of its fetal promoter.
Overexpression of IGF2 accelerates formation of liver tumors in mice with hepatic
expression of MYC and AKT1, via activation of IGF1 receptor signaling. An
antibody against IGF1 and IGF2 slows growth of xenograft tumors and increases
survival of these mice.
PMID- 27614048
TI - Going native: Complete removal of protein purification affinity tags by simple
modification of existing tags and proteases.
AB - Protein purification typically involves expressing a recombinant gene comprising
a target protein fused to a suitable affinity tag. After purification, it is
often desirable to remove the affinity tag to prevent interference with
downstream functions of the target protein. This is mainly accomplished by
placing a protease site between the tag and the target protein. Typically, a
small oligopeptide 'stub' C-terminal to the cleavage site remains attached to the
target protein due to the requirements of sequence-specific proteases.
Furthermore, steric hindrance can also limit protease efficiency. Here, we show
that respectively fusing the interacting ePDZ-b/ARVCF protein-peptide pair to the
target protein and a protease enables efficient processing of a minimised
sequence comprising only residues N-terminal to the cleavage site. Interaction of
the protein-peptide pair enforces proximity of the protease and its minimised
cleavage sequence, enhancing both catalysis of a sub-optimal site and overcoming
steric hindrance. This facilitates the high yield purification of fully native
target proteins without recourse to specialised purification columns.
PMID- 27614049
TI - Targeted mutagenesis of a conserved anther-expressed P450 gene confers male
sterility in monocots.
AB - Targeted mutagenesis using programmable DNA endonucleases has broad applications
for studying gene function in planta and developing approaches to improve crop
yields. Recently, a genetic method that eliminates the need to emasculate the
female inbred during hybrid seed production, referred to as Seed Production
Technology, has been described. The foundation of this genetic system relied on
classical methods to identify genes critical to anther and pollen development.
One of these genes is a P450 gene which is expressed in the tapetum of anthers.
Homozygous recessive mutants in this gene render maize and rice plants male
sterile. While this P450 in maize corresponds to the male fertility gene Ms26,
male fertility mutants have not been isolated in other monocots such as sorghum
and wheat. In this report, a custom designed homing endonuclease, Ems26+, was
used to generate in planta mutations in the rice, sorghum and wheat orthologs of
maize Ms26. Similar to maize, homozygous mutations in this P450 gene in rice and
sorghum prevent pollen formation resulting in male sterile plants and fertility
was restored in sorghum using a transformed copy of maize Ms26. In contrast,
allohexaploid wheat plants that carry similar homozygous nuclear mutations in
only one, but not all three, of their single genomes were male fertile. Targeted
mutagenesis and subsequent characterization of male fertility genes in sorghum
and wheat is an important step for capturing heterosis and improving crop yields
through hybrid seed.
PMID- 27614050
TI - Belief-bias reasoning in non-clinical delusion-prone individuals.
AB - BACKGROUND AND OBJECTIVES: It has been proposed that people with delusions have
difficulty inhibiting beliefs (i.e., "doxastic inhibition") so as to reason about
them as if they might not be true. We used a continuity approach to test this
proposal in non-clinical adults scoring high and low in psychometrically assessed
delusion-proneness. High delusion-prone individuals were expected to show greater
difficulty than low delusion-prone individuals on "conflict" items of a "belief
bias" reasoning task (i.e. when required to reason logically about statements
that conflicted with reality), but not on "non-conflict" items. METHODS: Twenty
high delusion-prone and twenty low delusion-prone participants (according to the
Peters et al. Delusions Inventory) completed a belief-bias reasoning task and
tests of IQ, working memory and general inhibition (Excluded Letter Fluency,
Stroop and Hayling Sentence Completion). RESULTS: High delusion-prone individuals
showed greater difficulty than low delusion-prone individuals on the Stroop and
Excluded Letter Fluency tests of inhibition, but no greater difficulty on the
conflict versus non-conflict items of the belief-bias task. They did, however,
make significantly more errors overall on the belief-bias task, despite
controlling for IQ, working memory and general inhibitory control. LIMITATIONS:
The study had a relatively small sample size and used non-clinical participants
to test a theory of cognitive processing in individuals with clinically diagnosed
delusions. CONCLUSIONS: Results failed to support a role for doxastic inhibitory
failure in non-clinical delusion-prone individuals. These individuals did,
however, show difficulty with conditional reasoning about statements that may or
may not conflict with reality, independent of any general cognitive or inhibitory
deficits.
PMID- 27614051
TI - Very low rate of patient-related adverse events associated with the use of
intraoperative cell salvage.
AB - BACKGROUND: The rate of patient-related clinical adverse events (AEs) associated
with the use of intraoperative cell salvage (ICS) was analyzed. STUDY DESIGN AND
METHODS: The perfusion service and electronic risk management databases in a nine
hospital regional health care system were reviewed over an approximately 11-year
period. The number of ICS cases performed during this period and basic patient
demographics were also extracted. RESULTS: There were 43,198 patients for whom
ICS was utilized during the study period. Recovered blood was returned to 33,351
(77.2%) patients. Electronic comments on the ICS procedure were found in 2348 of
33,351 (7.0%) cases. The vast majority of comments (2203/2348, 93.8%) described
minor events that did not lead to patient-related AEs such as the surgeon
requested higher than normal suction pressure or that no RBCs were returned. Only
144 of 2348 (6.1%) of the comments described procedural or equipment-related
events or potential AEs. From these comments two potential AEs were identified:
the first was a post-Cesarean section patient who became acutely tachycardic,
hypertensive, and dyspneic with rigors. The second was a patient with postpartum
hemorrhage who experienced acute dyspnea and hypotension. Both patients were
rapidly stabilized and discharged from the hospital shortly thereafter without
further complications. It is unclear if these events were caused by ICS
reinfusion. No air emboli were reported. The overall rate of patient-related AEs
associated with ICS reinfusion was between 0 and 2 per 33,351 (0%-0.006%).
CONCLUSIONS: The use of ICS is safe with a very low rate of patient-related AEs.
PMID- 27614053
TI - When do gamblers help themselves? Self-discontinuity increases self-directed
change over time.
AB - Most disordered gamblers fail to take the necessary action to change their
behavior. When action is taken, it is typically done under self-direction. Yet,
little is known about what motivates gamblers to engage in self-directed change
as researchers have focused almost exclusively on barriers to treatment seeking.
Herein, we tested whether self-discontinuity (i.e., the notion that the self has
undergone fundamental changes as a result of one's gambling) predicts self
directed change among gamblers experiencing sub-clinical levels of disordered
gambling. Further, we tested whether this relationship would hold when
controlling for feelings of shame and guilt about one's gambling as well as self
stigma as a disordered gambler (i.e., known barriers to change). To this end, 195
gamblers from the community completed a questionnaire battery that contained the
variables of interest. Six months later, participants were re-contacted to assess
whether they engaged in self-directed change. As hypothesized, the likelihood
that self-directed change was attempted increased to the extent participants
reported feeling self-discontinuous - an effect that remained significant when
controlling for shame, guilt, and self-stigma. Results suggest that heightening
the awareness that the gambling has fundamentally changed the self increases the
likelihood of gamblers taking action to change their disordered gambling
behaviors.
PMID- 27614052
TI - Alcohol perceptions and behavior in a residential peer social network.
AB - Personalized normative feedback is a recommended component of alcohol
interventions targeting college students. However, normative data are commonly
collected through campus-based surveys, not through actual participant-referent
relationships. In the present investigation, we examined how misperceptions of
residence hall peers, both overall using a global question and those designated
as important peers using person-specific questions, were related to students'
personal drinking behaviors. Participants were 108 students (88% freshman, 54%
White, 51% female) residing in a single campus residence hall. Participants
completed an online baseline survey in which they reported their own alcohol use
and perceptions of peer alcohol use using both an individual peer network measure
and a global peer perception measure of their residential peers. We employed
network autocorrelation models, which account for the inherent correlation
between observations, to test hypotheses. Overall, participants accurately
perceived the drinking of nominated friends but overestimated the drinking of
residential peers. Consistent with hypotheses, overestimating nominated friend
and global residential peer drinking predicted higher personal drinking, although
perception of nominated peers was a stronger predictor. Interaction analyses
showed that the relationship between global misperception and participant self
reported drinking was significant for heavy drinkers, but not non-heavy drinkers.
The current findings explicate how student perceptions of peer drinking within an
established social network influence drinking behaviors, which may be used to
enhance the effectiveness of normative feedback interventions.
PMID- 27614054
TI - Differences in alcohol use patterns between adolescent Asian American ethnic
groups: Representative estimates from the National Survey on Drug Use and Health
2002-2013.
AB - OBJECTIVE: Studies have suggested that alcohol use prevalence is increasing among
Asian American adolescents and there may be significant differences between
specific adolescent Asian American ethnicities. METHOD: Data from the National
Survey on Drug Use and Health (2002-2013) were used to estimate prevalence of
alcohol use (lifetime, past-month, past-year) and problem (binge drinking,
alcohol use disorder [AUD], and early initiation of use) outcomes among
adolescent Asian American ethnicities. RESULTS: Filipino Americans had the
highest prevalence of lifetime (29.3%) and past-month (10.3%) use; Korean
Americans had the highest prevalence of past-year use (22.7%). Asian Indian
Americans had the lowest prevalence of all three use indicators: 14.6%, 11.9%,
and 4.9% for lifetime, past-year, and past-month, respectively. Korean Americans
had the highest prevalence of binge drinking (5.4%), Filipino Americans had the
highest prevalence of AUD (3.5%), and Vietnamese Americans had the highest
prevalence of early initiation of use (13.5%). Asian Indian Americans had the
lowest prevalence for all three alcohol problem indicators: 2.6%, 1.0%, and 4.9%
for binge drinking, AUD, and early initiation of use, respectively. CONCLUSIONS:
Prevalence estimates of alcohol outcomes among Korean, Japanese, and Filipino
American adolescents were high and similar to other racial groups that are often
considered higher risk racial groups. Estimates among large subgroups with low
alcohol use prevalence, Chinese and Asian Indian Americans, may mask high rates
among other Asian ethnicities when alcohol use estimates are presented among
Asians overall. When feasible, researchers should present alcohol use estimates
disaggregated by specific Asian American ethnicities and investigate differences
in risk factors across groups.
PMID- 27614056
TI - The Drug Abuse Screening Test preserves its excellent psychometric properties in
psychiatric patients evaluated in an emergency setting.
AB - BACKGROUND: Substance use disorders (SUDs) are significant risk factors for
psychiatric relapses and hospitalizations in psychiatric populations.
Unfortunately, no instrument has been validated for the screening of SUDs in
psychiatric emergency settings. The Drug Abuse Screening Test (DAST) is widely
used in the addiction field, but is has not been validated in that particular
context. The objective of the current study is to examine the psychometric
properties of the DAST administered to psychiatric populations evaluated in an
emergency setting. METHODS: The DAST was administered to 912 psychiatric patients
in an emergency setting, of which 119 had a SUD (excluding those misusing alcohol
only). The internal consistency, the construct validity, the test-retest
reliability and the predictive validity (using SUD diagnoses) of the DAST were
examined. The convergent validity was also examined, using a validated
impulsivity scale. RESULTS: Regarding the internal consistency of the DAST, the
Cronbach's alpha was 0.88. The confirmatory factor analysis showed that the DAST
has one underlying factor. The test-retest reliability analysis produced a
correlation coefficient of 0.86. ROC curve analyses produced an area under the
curve of 0.799. Interestingly, a sex effect was observed. Finally, the convergent
validity analysis showed that the DAST total score is specifically correlated
with the sensation seeking dimension of impulsivity. DISCUSSION: The results of
this validation study shows that the DAST preserves its excellent psychometric
properties in psychiatric populations evaluated in an emergency setting. These
results should encourage the use of the DAST in this unstable clinical situation.
PMID- 27614055
TI - Income generation and attitudes towards addiction treatment among people who use
illicit drugs in a Canadian setting.
AB - INTRODUCTION: Socioeconomically marginalized people who use illicit drugs (PWUD)
often engage in alternative income generating activities to meet their basic
needs. These activities commonly carry a number of health and social risks, which
may prompt some PWUD to consider addiction treatment to reduce their drug use or
drug-related expenses. We sought to determine whether engaging in certain forms
of income generation was independently associated with self-reported need for
addiction treatment among a cohort of PWUD in Vancouver, Canada. METHODS: Data
from two prospective cohorts of PWUD in Vancouver were used in generalized
estimating equations to identify factors associated with self-reported need for
addiction treatment, with a focus on income generating activities. RESULTS:
Between June 2013 and May 2014, 1285 respondents participated in the study of
whom 483 (34.1%) were female and 396 (30.8%) indicated that they needed addiction
treatment. In final multivariate analyses, key factors significantly and
positively associated with self-reported need for addiction treatment included
engaging in illegal income generating activities (adjusted odds ratio [AOR]=1.96,
95% confidence interval [CI}: 1.11-3.46); sex work (AOR=1.61, 95% CI: 1.05-2.47),
homelessness (AOR=1.65, 95% CI: 1.22-2.25); and recent engagement in counselling
(AOR=1.85, 95% CI: 1.40-2.44). DISCUSSION: Our results suggest that key markers
of socioeconomic marginalization are strongly linked with a stated need for
addiction treatment. These findings underscore the need to provide appropriate
and accessible addiction treatment access to marginalized PWUD and to consider
alternative approaches to reduce socioeconomic disadvantage.
PMID- 27614057
TI - Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation in First
Complete Remission Can Abrogate the Poor Outcomes of Children with Acute Myeloid
Leukemia Resistant to the First Course of Induction Chemotherapy.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy
option for children with acute myeloid leukemia (AML) resistant to the first
course of induction chemotherapy (IC1st). We aimed to identify the efficacy of
unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first
complete remission and whether children resistant (IC1st-resistant; n = 38) or
sensitive (IC1st-sensitive; n = 59) to the IC1st can achieve comparable outcomes.
The cumulative incidence of grades III to IV acute graft-versus-host disease
(GVHD) and severe chronic GVHD was .0% versus 20.1% (P = .038) and 21.7% versus
13.2% (P = .238), respectively, for the IC1st-resistant and IC1st-sensitive
groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was
22.2% versus 7.6% (P = .061) and 5.3% versus 10.8% (P = .364), respectively, for
the IC1st-resistant and IC1st-sensitive groups. The 3-year probability of overall
survival and disease-free survival was 76.3% versus 83.0% (P = .657) and 72.5%
versus 81.6% (P = .396), respectively, for the IC1st-resistant and IC1st
sensitive groups. Multivariate analysis failed to show significant differences in
survival rates between the groups. Thus, our results show that unmanipulated
haplo-HSCT may overcome the poor prognostic significance of IC1st-resistance in
children with AML, and it is valid as a postremission treatment for children with
IC1st-resistant AML lacking an HLA-matched donor.
PMID- 27614058
TI - Translating QT interval prolongation from conscious dogs to humans.
AB - AIM: In spite of screening procedures in early drug development, uncertainty
remains about the propensity of new chemical entities (NCEs) to prolong the
QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive
in vitro proarrhythmia assay does not fully account for pharmacokinetic
pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated
the correlation between drug-specific parameters describing QT interval
prolongation in dogs and in humans. METHODS: Using estimates of the drug-specific
parameter, data on the slopes of the PKPD relationships of nine compounds with
varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat,
GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean
slope estimates varied between -0.98 ms MUM-1 and 6.1 ms MUM-1 in dogs and -10 ms
MUM-1 and 90 ms MUM-1 in humans, indicating a wide range of effects on the QT
interval. Linear regression techniques were then applied to characterize the
correlation between the parameter estimates across species. RESULTS: For
compounds without a mixed ion channel block, a correlation was observed between
the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R2 = 0.989).
These results show that per unit concentration, the drug effect on the QT
interval in humans is 11.6-fold larger than in dogs. CONCLUSIONS: Together with
information about the expected therapeutic exposure, the evidence of a
correlation between the compound-specific parameter in dogs and in humans
represents an opportunity for translating preclinical safety data before
progression into the clinic. Whereas further investigation is required to
establish the generalizability of our findings, this approach can be used with
clinical trial simulations to predict the probability of QT prolongation in
humans.
PMID- 27614059
TI - LDL receptor-related protein 1 contributes to the clearance of the activated
factor VII-antithrombin complex.
AB - : Essentials Factor VIIa is cleared principally as a complex with antithrombin.
Enzyme/serpin complexes are preferred ligands for the scavenger-receptor LRP1.
Factor VIIa/antithrombin but not factor VIIa alone is a ligand for LRP1.
Macrophage-expressed LRP1 contributes to the clearance of factor
VIIa/antithrombin. SUMMARY: Background Recent findings point to activated factor
VII (FVIIa) being cleared predominantly (+/- 65% of the injected protein) as part
of a complex with the serpin antithrombin. FVIIa-antithrombin complexes are
targeted to hepatocytes and liver macrophages. Both cells lines abundantly
express LDL receptor-related protein 1 (LRP1), a scavenger receptor mediating the
clearance of protease-serpin complexes. Objectives To investigate whether FVIIa
antithrombin is a ligand for LRP1. Methods Binding of FVIIa and pre-formed FVIIa
antithrombin to purified LRP1 Fc-tagged cluster IV (rLRP1-cIV/Fc) and to human
and murine macrophages was analyzed. FVIIa clearance was determined in macrophage
LRP1 (macLRP1)-deficient mice. Results Solid-phase binding assays showed that
FVIIa-antithrombin bound in a specific, dose-dependent and saturable manner to
rLRP1-cIV/Fc. Competition experiments with human THP1 macrophages indicated that
binding of FVIIa but not of FVIIa-antithrombin was reduced in the presence of
annexin-V or anti-tissue factor antibodies, whereas binding of FVIIa-antithrombin
but not FVIIa was inhibited by the LRP1-antagonist GST-RAP. Additional
experiments revealed binding of both FVIIa and FVIIa-antithrombin to murine
control macrophages. In contrast, no binding of FVIIa-antithrombin to macrophages
derived from macLRP1-deficient mice could be detected. Clearance of FVIIa
antithrombin but not of active site-blocked FVIIa was delayed 1.5-fold (mean
residence time of 3.3 +/- 0.1 h versus 2.4 +/- 0.2 h) in macLRP1-deficient mice.
The circulatory presence of FVIIa was prolonged to a similar extent in macLRP1
deficient mice and in control mice. Conclusions Our data show that FVIIa
antithrombin but not FVIIa is a ligand for LRP1, and that LRP1 contributes to the
clearance of FVIIa-antithrombin in vivo.
PMID- 27614061
TI - Electron transfer between carotenoid and chlorophyll contributes to quenching in
the LHCSR1 protein from Physcomitrella patens.
AB - Plants harvest photons for photosynthesis using light-harvesting complexes (LHCs)
an array of chlorophyll proteins that can reversibly switch from harvesting to
energy-dissipation mode to prevent over-excitation and damage of the
photosynthetic apparatus. In unicellular algae and lower plants this process
requires the LHCSR proteins which senses over-acidification of the lumen trough
protonatable residues exposed to the thylakoid lumen to activate quenching
reactions. Further activation is provided by replacement of the violaxanthin
ligand with its de-epoxidized product, zeaxanthin, also induced by excess light.
We have produced the ppLHCSR1 protein from Physcomitrella patens by over
expression in tobacco and purified it in either its violaxanthin- or the
zeaxanthin-binding form with the aim of analyzing their spectroscopic properties
at either neutral or acidic pH. Using femtosecond spectroscopy, we demonstrated
that the energy dissipation is achieved by two distinct quenching mechanism which
are both activated by low pH. The first is present in both ppLHCSR1-Vio and
ppLHCSR1-Zea and is characterized by 30-40ps time constant. The spectrum of the
quenching product is reminiscent of a carotenoid radical cation, suggesting that
the pH-induced quenching mechanism is likely electron transfer from the
carotenoid to the excited Chl a. In addition, a second quenching channel
populating the S1 state of carotenoid via energy transfer from Chl is found
exclusively in the ppLHCSR1-Zea at pH5. These results provide proof of principle
that more than one quenching mechanism may operate in the LHC superfamily and
also help understanding the photoprotective role of LHCSR proteins and the
evolution of LHC antennae.
PMID- 27614060
TI - Directed assembly of defined oligomeric photosynthetic reaction centres through
adaptation with programmable extra-membrane coiled-coil interfaces.
AB - A challenge associated with the utilisation of bioenergetic proteins in new,
synthetic energy transducing systems is achieving efficient and predictable self
assembly of individual components, both natural and man-made, into a functioning
macromolecular system. Despite progress with water-soluble proteins, the
challenge of programming self-assembly of integral membrane proteins into non
native macromolecular architectures remains largely unexplored. In this work it
is shown that the assembly of dimers, trimers or tetramers of the naturally
monomeric purple bacterial reaction centre can be directed by augmentation with
an alpha-helical peptide that self-associates into extra-membrane coiled-coil
bundle. Despite this induced oligomerisation the assembled reaction centres
displayed normal spectroscopic properties, implying preserved structural and
functional integrity. Mixing of two reaction centres modified with mutually
complementary alpha-helical peptides enabled the assembly of heterodimers in
vitro, pointing to a generic strategy for assembling hetero-oligomeric complexes
from diverse modified or synthetic components. Addition of two coiled-coil
peptides per reaction centre monomer was also tolerated despite the challenge
presented to the pigment-protein assembly machinery of introducing multiple self
associating sequences. These findings point to a generalised approach where
oligomers or longer range assemblies of multiple light harvesting and/or redox
proteins can be constructed in a manner that can be genetically-encoded, enabling
the construction of new, designed bioenergetic systems in vivo or in vitro.
PMID- 27614062
TI - Geographical disparities in access to cancer management and treatment services in
England.
AB - This study seeks to examine the extent to which cancer services are
geographically located according to cancer incidence, and assess the association
with cancer survival. We identified hospital sites serving English PCTs (Primary
Care Trusts) with the management and treatment of breast, lung and colorectal
cancer. Geographical access was estimated as travel time in minutes from LSOAs
(Lower Super Output Areas) to the nearest hospital site and aggregated to PCT
level. Correlations between PCT level mean travel times and cancer cases were
estimated using Spearman's rank correlation. Associations between PCT level mean
travel times and cancer relative survival rates were estimated using linear
regression with adjustment for area deprivation and for a PCT level measure of
the reported ease of obtaining a doctor's appointment. We found that cancer
services tended to be located farther from areas with more cancer cases, and
longer average travel times are associated with worse survival after adjustment
for age, sex, year and area deprivation. This suggests that geographical access
to cancer services remains a concern in England.
PMID- 27614063
TI - The effects of built environment attributes on physical activity-related health
and health care costs outcomes in Australia.
AB - Attributes of the built environment can positively influence physical activity of
urban populations, which results in health and economic benefits. In this study,
we derived scenarios from the literature for the association built environment
physical activity and used a mathematical model to translate improvements in
physical activity to health-adjusted life years and health care costs. We
modelled 28 scenarios representing a diverse range of built environment
attributes including density, diversity of land use, availability of
destinations, distance to transit, design and neighbourhood walkability. Our
results indicated potential health gains in 24 of the 28 modelled built
environment attributes. Health care cost savings due to prevented physical
activity-related diseases ranged between A$1300 to A$105,355 per 100,000 adults
per year. On the other hand, additional health care costs of prolonged life years
attributable to improvements in physical activity were nearly 50% higher than the
estimated health care costs savings. Our results give an indication of the
potential health benefits of investing in physical activity-friendly built
environments.
PMID- 27614065
TI - Memory-dependent effects on palatability in mice.
AB - While palatability depends on the properties of particular foods, it is also
determined by prior experience, suggesting that memory affects the hedonic value
of a substance. Here, we report two procedures that affect palatability in mice:
negative contrast and flavour habituation. A microstructure analysis of licking
behaviour was employed, with the lick cluster size (the number of licks made in
quick succession before a pause) used as a measure of palatability. It was first
confirmed that lick cluster size increased monotonically as a function of sucrose
concentration, whereas consumption followed an inverted U-shaped function. In a
successive negative contrast procedure it was found that when shifted from a high
sucrose concentration (32%) to a low sucrose concentration (4%), mice made
smaller lick clusters than a group that only received the low concentration. Mice
exposed to flavours (cherry or grape Kool Aid) mixed with sucrose (16%) made
larger lick clusters for familiar flavours compared to novel flavours. This
habituation effect was evident after short (5min) and long (24h) test intervals.
Both successive negative contrast and flavour habituation failed to affect levels
of consumption. Collectively, the results show that prior experience can have
effects on lick cluster size that are equivalent to increasing or decreasing the
sweetness of a solution. Thus, palatability is not a fixed property of a
substance but is dependent on expectation or familiarity that occurs as a result
of memory.
PMID- 27614066
TI - Unexpected release of phosphate and organic carbon to streams linked to declining
nitrogen depositions.
AB - Reductions in emissions have successfully led to a regional decline in
atmospheric nitrogen depositions over the past 20 years. By analyzing long-term
data from 110 mountainous streams draining into German drinking water reservoirs,
nitrate concentrations indeed declined in the majority of catchments.
Furthermore, our meta-analysis indicates that the declining nitrate levels are
linked to the release of dissolved iron to streams likely due to a reductive
dissolution of iron(III) minerals in riparian wetland soils. This dissolution
process mobilized adsorbed compounds, such as phosphate, dissolved organic carbon
and arsenic, resulting in concentration increases in the streams and higher
inputs to receiving drinking water reservoirs. Reductive mobilization was most
significant in catchments with stream nitrate concentrations <6 mg L-1 . Here,
nitrate, as a competing electron acceptor, was too low in concentration to
inhibit microbial iron(III) reduction. Consequently, observed trends were
strongest in forested catchments, where nitrate concentrations were unaffected by
agricultural and urban sources and which were therefore sensitive to reductions
of atmospheric nitrogen depositions. We conclude that there is strong evidence
that the decline in nitrogen deposition toward pre-industrial conditions lowers
the redox buffer in riparian soils, destabilizing formerly fixed problematic
compounds, and results in serious implications for water quality.
PMID- 27614067
TI - Non-diagnostic coronary artery calcification and stenosis: a correlation of
coronary computed tomography angiography and invasive coronary angiography.
AB - Background Heavy coronary artery calcification (CAC) impairs diagnostic accuracy
of coronary computed tomography angiography (cCTA) and is considered to be a
major limitation. Purpose To investigate the effect of non-evaluable CAC seen on
cCTA on clinical decision-making by determining the degree of subsequent invasive
testing and to assess the relationship between non-evaluable segments containing
CAC and significant stenosis as seen in invasive coronary angiography (ICA).
Material and Methods The study comprised of 356 patients who underwent cCTA and
subsequent ICA within 2 months between 2005 and 2009. Clinical reports were
reviewed to identify the indications for referral to ICA. In a subset of 68
patients where non-diagnostic CAC on cCTA and significant stenosis on ICA were
present in the same segment, we correlated and analyzed the underlying stenosis
severity of the lesion on ICA to the cCTA. Lesions with CAC were analyzed in a
standardized fashion by application of reading rules. Results Non-diagnostic CAC
on cCTA prompted ICA in 5.6% of patients. CAC occurred at the site of maximum
stenosis in segments with stenosis <50% (95.9% [47/49]), 50-69% (82.4% [28/34]),
70-99% (64.5% [31/48]), and 100% (33.3% [1/3]). At the point of maximum calcium
deposit, non-obstructive disease was present in 61.2%. Application of reading
rules resulted in a 44% reduction in non-diagnostic cCTA reads. Conclusion Severe
CAC may prompt further investigation with ICA. There is less CAC with increasing
lesion severity at the point of maximum stenosis. Additional application of
reading rules improved non-diagnostic cCTA reads.
PMID- 27614064
TI - Associations of neighborhood socioeconomic and racial/ethnic characteristics with
changes in survey-based neighborhood quality, 2000-2011.
AB - We investigated the relationships between neighborhood socio-demographic
characteristics (socioeconomic status [SES], percentage of Black residents, and
percentage of Hispanic residents) and survey-based measures of the social
environment (social cohesion, safety) and the physical environment (healthy food
environment, walking environment) in six sites from 2000 through 2011.
Neighborhood environments were patterned by area SES and racial/ethnic
composition, such that higher SES and lower percentage minority neighborhoods had
better physical and social environments. Increasing disparities over time were
observed for some neighborhood environments. Further research should explore the
role of neighborhood environments in maintaining or increasing social disparities
in health.
PMID- 27614068
TI - Auditor recommendations resulting from three clinical audit rounds in Finnish
radiology units.
AB - Background The purpose of clinical audits performed in radiology units is to
reduce the radiation dose of patients and staff and to implement evidence-based
best practices. Purpose To describe auditor recommendations in three Finnish
clinical audit rounds performed in 2002-2014, and to determine if auditor
recommendations have had any impact on improving medical imaging practice.
Material and Methods The retrospective observational study was performed in
radiology units holding a radiation safety license issued by the Finnish
Radiation and Nuclear Safety Authority. The data comprised a systematic sample (n
= 120) of auditor reports produced in three auditing rounds in these units during
the years 2002-2014. The data were analyzed by descriptive methods and by using
the Friedman two-way ANOVA test. Results The number of auditor recommendations
given varied between clinical audit rounds and according to the type of imaging
unit, as well as according to calculation method. Proportionally, the most
recommendations in all three clinical audit rounds were given about defining and
using quality assurance functions and about guidelines and practices for carrying
out procedures involving radiation exposure. Demanding radiology units improved
their practices more than basic imaging units towards the third round. Conclusion
Auditor recommendations help to address the deficiencies in imaging practices.
There is a need to develop uniform guidelines and to provide tutoring for
clinical auditors in order to produce comparable clinical audit results.
PMID- 27614069
TI - A free software for the calculation of T2* values for iron overload assessment.
AB - Background Iron overload assessment with magnetic resonance imaging (MRI) using
T2* has become a key diagnostic method in the management of many diseases.
Quantitative analysis of the MRI images with a cost-effective tool has been a
limitation to increased use of the method. Purpose To provide a free software
solution for this purpose comparing the results with a commercial solution.
Material and Methods The free tool was developed as a standalone program to be
directly downloaded and ran in a common personal computer platform without the
need of a dedicated workstation. Liver and cardiac T2* values were calculated
using both tools and the values obtained compared between them in a group of 56
patients with suspected iron overload using Bland-Altman plots and concordance
correlation coefficients (CCC). Results In the heart, the mean T2* differences
between the two methods was 0.46 ms (95% confidence interval [CI], -0.037 -0.965)
and in the liver 0.49 ms (95% CI, 0.257-0.722). The CCC for both the heart and
the liver were significantly high (0.98 [95% CI, 0.966-0.988] with a Pearson rho
of 0.9811 and 0.991 [95% CI, 0.986-0.994] with a Pearson rho of 0.996,
respectively. No significant differences were observed when analyzing only
patients with abnormal concentrations of iron in both organs compared to the
whole cohort. Conclusion The proposed free software tool is accurate for
calculation of T2* values of the liver and heart and might be a solution for
centers that cannot use paid commercial solutions.
PMID- 27614070
TI - Editorial Compilation-II.
PMID- 27614071
TI - Giuseppe (Joseph) Favaloro (1922-2016).
PMID- 27614073
TI - SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled
alternative splicing.
AB - Trimethylation of histone H3K36 is a chromatin mark associated with active gene
expression, which has been implicated in coupling transcription with mRNA
splicing and DNA damage response. SETD2 is a major H3K36 trimethyltransferase,
which has been implicated as a tumor suppressor in mammals. Here, we report the
regulation of SETD2 protein stability by the proteasome system, and the
identification of SPOP, a key subunit of the CUL3 ubiquitin E3 ligase complex, as
a SETD2-interacting protein. We demonstrate that SPOP is critically involved in
SETD2 stability control and that the SPOP/CUL3 complex is responsible for SETD2
polyubiquitination both in vivo and in vitro ChIP-Seq analysis and biochemical
experiments demonstrate that modulation of SPOP expression confers differential
H3K36me3 on SETD2 target genes, and induce H3K36me3-coupled alternative splicing
events. Together, these findings establish a functional connection between
oncogenic SPOP and tumor suppressive SETD2 in the dynamic regulation of gene
expression on chromatin.
PMID- 27614076
TI - Self-rated health predicts decline in instrumental activities of daily living
among high-functioning community-dwelling older people.
AB - Background: self-rated health (SRH) is a strong predictor of mortality, but it is
unclear if SRH independently predicts a decline in instrumental activities of
daily living (IADL). Objective: to verify whether SRH is an independent predictor
of IADL decline. Design: a population-based longitudinal cohort study. Setting:
two local municipalities in Nara, Japan. Subjects: community-dwelling older
adults 65 years or older (2,638 males and 3,346 females) with independent IADL at
baseline. Methods: SRH was assessed using a single-item measure. IADL was
assessed using the Tokyo Metropolitan Institute of Gerontology Index of
Competence. Multiple logistic regressions were used to examine the association of
SRH with IADL decline. Results: during the 3-year follow-up, 13.2% of males and
8.2% of females developed IADL decline. After adjusting for age, family, body
mass index, economic situations, chronic diseases, alcohol, smoking, depression,
cognitive functioning and ADL, poorer SHR was significantly associated with IADL
decline in both genders. Compared with very good SRH, the odds ratios of good,
poor and very poor were 1.69 (95% confidence interval: 1.14-2.51), 2.10 (1.25
3.55) and 3.11 (1.50-6.45) for males, and 0.88 (0.54-1.42), 2.08 (1.16-3.75) and
3.42 (1.57-7.42) for females, respectively. Significant associations were not
affected by chronic diseases, cognitive functioning or ADL but observed only
among subjects aged 65-74 or those without depression. Conclusions: this study
confirms that SRH is an independent predictor of IADL decline among non-disabled
community-dwelling older adults. Our findings suggest that SRH is an effective
tool for identifying older people with future risk for IADL decline, particularly
among the young-old or those without depression.
PMID- 27614072
TI - TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into
an endogenous miRNA locus.
AB - Successful RNAi applications depend on strategies allowing robust and persistent
expression of minimal gene silencing triggers without perturbing endogenous gene
expression. Here, we propose a novel avenue which is integration of a
promoterless shmiRNA, i.e. a shRNA embedded in a micro-RNA (miRNA) scaffold, into
an engineered genomic miRNA locus. For proof-of-concept, we used TALE or
CRISPR/Cas9 nucleases to site-specifically integrate an anti-hepatitis C virus
(HCV) shmiRNA into the liver-specific miR-122/hcr locus in hepatoma cells, with
the aim to obtain cellular clones that are genetically protected against HCV
infection. Using reporter assays, Northern blotting and qRT-PCR, we confirmed
anti-HCV shmiRNA expression as well as miR-122 integrity and functionality in
selected cellular progeny. Moreover, we employed a comprehensive battery of PCR,
cDNA/miRNA profiling and whole genome sequencing analyses to validate targeted
integration of a single shmiRNA molecule at the expected position, and to rule
out deleterious effects on the genomes or transcriptomes of the engineered cells.
Importantly, a subgenomic HCV replicon and a full-length reporter virus, but not
a Dengue virus control, were significantly impaired in the modified cells. Our
original combination of DNA engineering and RNAi expression technologies benefits
numerous applications, from miRNA, genome and transgenesis research, to human
gene therapy.
PMID- 27614075
TI - Probing RNA recognition by human ADAR2 using a high-throughput mutagenesis
method.
AB - Adenosine deamination is one of the most prevalent post-transcriptional
modifications in mRNA. In humans, ADAR1 and ADAR2 catalyze this modification and
their malfunction correlates with disease. Recently our laboratory reported
crystal structures of the human ADAR2 deaminase domain bound to duplex RNA
revealing a protein loop that binds the RNA on the 5' side of the modification
site. This 5' binding loop appears to be one contributor to substrate specificity
differences between ADAR family members. In this study, we endeavored to reveal
detailed structure-activity relationships in this loop to advance our
understanding of RNA recognition by ADAR2. To achieve this goal, we established a
high-throughput mutagenesis approach which allows rapid screening of ADAR
variants in single yeast cells and provides quantitative evaluation for enzymatic
activity. Using this approach, we determined the importance of specific amino
acids at 19 different positions in the ADAR2 5' binding loop and revealed six
residues that provide essential structural elements supporting the fold of the
loop and key RNA-binding functional groups. This work provided new insight into
RNA recognition by ADAR2 and established a new tool for defining structure
function relationships in ADAR reactions.
PMID- 27614082
TI - Frontal fibrosing alopecia: there is no statistically significant association
with leave-on facial skin care products and sunscreens.
PMID- 27614077
TI - Comprehensive geriatric assessment: recognition of identified geriatric
conditions by community-dwelling older persons.
AB - OBJECTIVES: to study (i) the prevalence of geriatric conditions in community
dwelling older persons at increased risk of functional decline and (ii) the
extent to which older persons recognise comprehensive geriatric assessment (CGA)
identified conditions as relevant problems. METHODS: trained registered nurses
conducted a CGA in 934 out of 1209 older persons at increased risk of functional
decline participating in the intervention arm of a randomised trial in the
Netherlands. After screening for 32 geriatric conditions, participants were asked
which of the identified geriatric conditions they recognised as relevant
problems. RESULTS: at baseline, the median age of participants was 82.9 years
(interquartile range (IQR) 77.3-87.3 years). The median number of identified
geriatric conditions per participant was 8 (IQR 6-11). The median number of
geriatric conditions that were recognised was 1 (IQR 0-2). Functional dependency
and (increased risk of) alcohol and drug dependency were the most commonly
identified conditions. Pain was the most widely recognised problem. CONCLUSION:
CGA identified many geriatric conditions, of which few were recognised as a
problem by the person involved. Further study is needed to better understand how
older persons interact with identified geriatric conditions, in terms of
perceived relevance. This may yield a more efficient CGA and further improve a
patient-centred approach.
PMID- 27614083
TI - Accumulation of Deleterious Mutations on the Neo-Y Chromosome of Japan Sea
Stickleback (Gasterosteus nipponicus).
AB - Degeneration of Y chromosomes is a common evolutionary path of XY sex chromosome
systems. Recent genomic studies in flies and plants have revealed that even young
neo-sex chromosomes with the age of a few million years show signs of Y
degeneration, such as the accumulation of nonsense and frameshift mutations.
However, it remains unclear whether neo-Y chromosomes also show rapid
degeneration in fishes, which often have homomorphic sex chromosomes. Here, we
investigated whether a neo-Y chromosome of Japan Sea stickleback (Gasterosteus
nipponicus), which was formed by a Y-autosome fusion within the last 2 million
years, accumulates deleterious mutations. Our previous genomic analyses did not
detect excess nonsense and frameshift mutations on the Japan Sea stickleback neo
Y. In the present study, we found that the nonrecombining region of the neo-Y
near the fusion end has accumulated nonsynonymous mutations altering amino acids
of evolutionarily highly conserved residues. Enrichment of gene ontology terms
related to protein phosphorylation and cellular protein modification process was
found in the genes with potentially deleterious mutations on the neo-Y. These
results suggest that the neo-Y of the Japan Sea stickleback has already
accumulated mutations that may impair protein functions.
PMID- 27614084
TI - Evaluating the impact of a national naloxone programme on ambulance attendance at
overdose incidents: a controlled time-series analysis.
AB - BACKGROUND AND AIMS: It has been suggested that distributing naloxone to people
who inject drugs (PWID) will lead to fewer attendances by emergency medical
services at opioid-related overdose incidents if peer administration of naloxone
was perceived to have resuscitated the overdose victim successfully. This study
evaluated the impact of a national naloxone programme (NNP) on ambulance
attendance at opioid-related overdose incidents throughout Scotland.
Specifically, we aimed to answer the following research questions: is there
evidence of an association between ambulance call-outs to opioid-related overdose
incidents and the cumulative number of 'take-home naloxone' (THN) kits in issue;
and is there evidence of an association between ambulance call-outs to opioid
related overdose incidents in early adopter (pilot) or later adopting (non-pilot)
regions and the cumulative number of THN kits issued in those areas? DESIGN:
Controlled time-series analysis. SETTING: Scotland, UK, 2008-15. PARTICIPANTS:
Pre-NNP implementation period for the evaluation was defined as 1 April 2008 to
31 March 2011 and the post-implementation period as 1 April 2011 to 31 March
2015. In total, 3721 ambulance attendances at opioid-related overdose were
recorded for the pre-NNP implementation period across 158 weeks (mean 23.6
attendances per week) and 5258 attendances across 212 weeks in the post
implementation period (mean 24.8 attendances per week). INTERVENTION: Scotland's
NNP; formally implemented on 1 April 2011. MEASUREMENTS: Primary outcome measure
was weekly incidence (counts) of call-outs to opioid-related overdoses at
national and regional Health Board level. Data were acquired from the Scottish
Ambulance Service (SAS). Models were adjusted for opioid replacement therapy
using data acquired from the Information Services Division on monthly sums of all
dispensed methadone and buprenorphine in the study period. Models were adjusted
further for a control group: weekly incidence (counts) of call-outs to heroin
related overdose in the London Borough area acquired from the London Ambulance
Service. FINDINGS: There was no significant association between SAS call-outs to
opioid-related overdose incidents and THN kits in issue for Scotland as a whole
(coefficient 0.009, 95% confidence intervals = -0.01, 0.03, P = 0.39). In
addition, the magnitude of association between THN kits and SAS call-outs did not
differ significantly between pilot and non-pilot regions (interaction test, P =
0.62). CONCLUSIONS: The supply of take-home naloxone kits through a National
Naloxone Programme in Scotland was not associated clearly with a decrease in
ambulance attendance at opioid-related overdose incidents in the 4-year period
after it was implemented in April 2011.
PMID- 27614086
TI - Values of radiological examinations for the diagnosis and prognosis of invasive
bronchial-pulmonary aspergillosis in critically ill patients with chronic
obstructive pulmonary diseases.
AB - INTRODUCTION: The important role of radiological examinations of invasive
pulmonary aspergillosis (IPA) in patients with neutropenia has been well studied;
however, little is known about IPA in critically ill chronic obstructive
pulmonary disease (COPD) patients. OBJECTIVES: To evaluate the value of
radiological examinations in the diagnosis and prognosis of invasive bronchial
pulmonary aspergillosis (IBPA) in critically ill COPD patients. METHODS: We
included 61 critically ill COPD patients in the intensive care unit (ICU) in a
retrospective, single-center cohort study. RESULTS: All of the patients were
classified as IBPA group (n = 21) or non-IBPA group (n = 40). The chest computed
tomography (CT) image analysis showed that the IBPA group had the highest percent
of patchiness (76.2%), followed by multiple nodules (33.3%), angio-invasive
patterns (including halo sign, wedge consolidation and air-crescent sign/cavity
with a relatively low percent of 19%, 19% and 28.5%, respectively), and the
multiple nodules that were distributed along the airway provided the most
specific image, with the highest specificity of 92.5%. Compared to the survivors
in the IBPA group, non-surviving patients had a higher percent of large
consolidation (0% vs. 45.5%, P = .035). When the new effusions appeared on a
chest x-ray (CXR), the creatinine (140.4 MUmol/L vs. 64.0 MUmol/L, P = .010) and
PaO2 /FiO2 (188 mm Hg vs. 222 mm Hg, P = .034) rate deteriorated. CONCLUSIONS:
Multiple nodules that were distributed along with broncho-vascular bundles were
relatively common and specific in critically ill COPD patients with IBPA.
Deteriorated CXR combined with specific laboratory examinations, even when
appropriate antibiotics were used, could indicate a diagnosis of IBPA. Large
consolidations might be considered as poor prognostic indicators.
PMID- 27614085
TI - Orthotopic tracheal transplantation using human bronchus: an original
xenotransplant model of obliterative airway disorder.
AB - Bronchiolitis obliterans syndrome (BOS) is a main cause of allograft dysfunction
and mortality after lung transplantation (LTx). A better understanding of BOS
pathogenesis is needed to overcome this treatment-refractory complication.
Orthotopic tracheal transplantation using human bronchus was performed in Brown
Norway (BN) and nude (RNU) rats. Allografts were recovered in both strains at Day
7 (BN7 , n = 6; RNU7 , n = 7) or Day 28 (BN28 , n = 6; RNU28 , n = 6). Immune
response of the host against the bronchial graft was assessed. Human samples from
BOS patients were used to compare with the histological features of the animal
model. Obstruction of the allograft lumen associated with significant
infiltration of CD3+ and CD68+ cells was observed in the BN group on Day 28.
Immune response from type 1 T-helper cells against the tracheal xenograft was
higher in BN animals compared to nude animals on Days 7 and 28 (P < 0.001 and P =
0.035). Xenoreactive antibodies were significantly higher at Day 7 (IgM) and Day
28 (IgG) in the BN group compared to RNU (respectively, 37.6 +/- 6.5 vs. 5.8 +/-
0.7 mean fluorescence, P = 0.039; and 22.4 +/- 3.8 vs. 6.9 +/- 1.6 mean
fluorescence, P = 0.011). Immunocompetent animals showed a higher infiltration of
S100A4+ cells inside the bronchial wall after 28 days, associated with cartilage
damage ranging from invasion to complete destruction. In vitro expression of
S100A4 by human fibroblasts was higher when stimulated by mononuclear cells
(MNCs) from BN rats than from RNU (2.9 +/- 0.1 vs. 2.4 +/- 0.1 mean fluorescence
intensity, P = 0.005). Similarly, S100A4 was highly expressed in response to
human MNCs compared to stimulation by T-cell-depleted human MNCs (4.3 +/- 0.2 vs.
2.7 +/- 0.1 mean fluorescence intensity, P < 0.001). Obliterative bronchiolitis
has been induced in a new xenotransplant model in which chronic airway
obstruction was associated with immune activation against the xenograft.
Cartilage infiltration by S100A4+ cells might be stimulated by T cells.
PMID- 27614088
TI - Stability in a changing world - palm community dynamics in the hyperdiverse
western Amazon over 17 years.
AB - Are the hyperdiverse local forests of the western Amazon undergoing changes
linked to global and local drivers such as climate change, or successional
dynamics? We analyzed local climatic records to assess potential climatic changes
in Yasuni National Park, Ecuador, and compared two censuses (1995, 2012) of a
palm community to assess changes in community structure and composition. Over 17
years, the structure and composition of this palm community remained remarkably
stable. Soil humidity was significantly lower and canopy conditions were
significantly more open in 2012 compared to 1995, but local climatic records
showed that no significant changes in precipitation, temperature or river level
have occurred during the last decade. Thus, we found no evidence of recent
directional shifts in climate or the palm community in Yasuni. The absence of
changes in local climate and plant community dynamics in Yasuni contrasts with
recent findings from eastern Amazon, where environmental change is driving
significant changes in ecosystem dynamics. Our findings suggest that until now,
local forests in the northwest Amazon may have escaped pressure from climate
change. The stability of this rich palm community embedded in the hyperdiverse
Yasuni National Park underlines its uniqueness as a sanctuary for the protection
of Amazonian diversity from global change impacts.
PMID- 27614087
TI - Preferential conduction block of myelinated axons by nitric oxide.
AB - Conduction block by nitric oxide (NO) was examined in myelinated and unmyelinated
axons from both the central nervous system and peripheral nervous system. In rat
vagus nerves, mouse optic nerves at P12-P23, adult and developing mouse sciatic
nerves, and mouse spinal cords, myelinated fibers were preferentially blocked
reversibly by concentrations of NO similar to those encountered in inflammatory
lesions. The possibility that these differences between myelinated and
unmyelinated axons are due to the normal developmental substitution of Na+
channel subtype Nav 1.6 for Nav 1.2 at nodes of Ranvier was tested by repeating
experiments on mice null for Nav 1.6. Results were unchanged in this mutant. In
shiverer optic nerve, which has only scattered regions with nodes of Ranvier,
only the fastest component of the compound action potential was reduced. NO was
compared with three other methods of blocking conduction: low Na+ , high K+ , and
tetrodotoxin (TTX). In each of these three cases, unmyelinated axons lost
conduction simultaneously with myelinated fibers. From changes in conduction
velocity in myelinated axons as they were blocked, it was ascertained that NO
acted most similarly to TTX. It was concluded that NO likely interacts with
axonal Na+ channels through an intermediate that is associated with myelin. (c)
2016 Wiley Periodicals, Inc.
PMID- 27614089
TI - The impact of serious adverse drug reactions: a population-based study of a
decade of hospital admissions in New South Wales, Australia.
AB - AIMS: Adverse drug reactions (ADRs) have major impacts on patients and the
hospital system. Methods identifying ADRs from selected International
Classification of Diseases-10th revision (ICD-10) diagnosis and external cause
codes can be applied to population-level hospital admissions data, enabling the
study of rare, yet serious ADRs. The present study aimed to use ICD10-based
methods to identify four types of serious idiosyncratic ADRs in Australia, and to
assess changes in incidence and their impact on length of stay (LOS), readmission
and in-hospital mortality. METHODS: The study used a census of hospital admission
data from New South Wales between July 2000 and June 2012. Changes in incidence
rates over time relative to a control group were estimated using log-linear
regression. To assess impacts on LOS, readmission and mortality, each ADR case
was matched with five controls, and cases were compared with controls via
generalized linear models appropriate to each outcome. RESULTS: The incidence of
three ADR types showed a significant increase over time relative to controls,
while the fourth type showed no evidence of change. All ADR types were
significantly associated with an increase in LOS of between 22% and 328%.
Significant increases in risk of readmission or death were only observed for some
ADR types. CONCLUSIONS: Reducing the incidence of idiosyncratic ADRs is
challenging. ICD10-based methods support population-level analyses that can
provide important insights into the effects and changes in ADRs over time. This,
combined with strategies related to both patient care and drug monitoring pre-
and post-commercial release, provides ways forward.
PMID- 27614090
TI - Redox proteomic evaluation of oxidative modification and recovery in a 3D
reconstituted human skin tissue model exposed to UVB.
AB - OBJECTIVE: Exposure to UV in humans resulting in sunburn triggers a complex
series of events that are a mix of immediate and delayed damage mediation and
healing. While studies on the effects of UV exposure on DNA damage and repair
have been reported, changes in the oxidative modification of skin proteins are
poorly understood at the molecular level, despite the important role played by
structural proteins in skin tissue, and the effect of the integrity of these
proteins on skin appearance and health. Proteomic molecular mapping of oxidation
was here applied to try to enhance understanding of skin damage and recovery from
oxidative damage and UVB exposure. METHODS: A redox proteomic-based approach was
applied to evaluating skin protein modification when exposed to varying doses of
UVB after initial oxidative stress, via tracking changes in protein oxidation
during the healing process in vitro using a full-thickness reconstituted human
skin tissue model. Bioassays and structural evaluation confirmed that our
cultured skin tissues underwent a normal physiological response to UVB exposure.
RESULTS: A set of potential skin marker peptides was generated, for use in
tracking skin protein oxidative modification. Exposure to UVB after thermal
oxidative stress was found to result in higher levels of skin protein oxidation
than a non-irradiated control for up to seven days after exposure. Recovery of
the skin proteins from oxidative stress, as assessed by the overall protein
oxidation levels, was found to be impaired by UVB exposure. Oxidative
modification was largely observed in skin structural proteins. CONCLUSION:
Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin
proteins, with higher exposure levels leading to increasingly impaired recovery
from this damage. This has potential implications for the functional performance
of the proteins and inter-related skin health and cosmetic appearance.
PMID- 27614092
TI - Sugars and organic acids in plum fruit affected by Plum pox virus.
AB - BACKGROUND: Plum pox virus (PPV) causes severe economic losses in stone fruit
production, but little is known about its effect on plum fruit composition. In
this study, the influence of PPV on sugars and organic acids was evaluated in a
susceptible plum (Prunus domestica L.) cultivar. RESULTS: PPV infection
significantly affected the content and composition of sugars and organic acids.
The composition of necrotic tissue was modified the most. A short-time infected
tree yielded fruit with similar sugar composition to fruit from a healthy tree,
but the decline of organic acids was faster. Prematurely ripened symptomatic
fruit had reduced fruit weight and low sugar content. CONCLUSION: Infected trees
of the studied cultivar produce fruit of inferior quality. Fruits are not
suitable for processing, especially when most of them exhibit visual symptoms of
PPV infection. (c) 2016 Society of Chemical Industry.
PMID- 27614093
TI - Receptor-interacting Protein 140 represses Sirtuin 3 to facilitate hypertrophy,
mitochondrial dysfunction and energy metabolic dysfunction in cardiomyocytes.
AB - AIM: The transcriptional cofactor receptor-interacting protein 140 (RIP140) is
known as a deleterious regulator of cardiac mitochondrial function and energy
metabolic homeostasis. This study revealed that RIP140 repressed Sirtuin 3
(SIRT3), a mitochondrial deacetylase that plays an important role in regulating
cardiac function. METHODS: RIP140 was overexpressed by adenovirus infection or
was knocked down by RNA interference in neonatal rat cardiomyocytes. RESULTS:
RIP140 overexpression repressed, while RIP140 silencing elevated the expression
and activity of SIRT3. Ad-RIP140 enhanced the expressions of the cardiac
hypertrophic markers and increased cardiomyocyte surface area, whereas SIRT3
overexpression prevented the effect of Ad-RIP140. Additionally, SIRT3
overexpression reversed Ad-RIP140-induced mitochondrial dysfunction and energy
metabolic dysfunction, such as increase in oxidative stress, decrease in
mitochondrial membrane potential and ATP production, as well as downregulation of
mitochondrial DNA-encoded genes and genes related to mitochondrial genome
replication and transcription, mitochondrial oxidative phosphorylation and fatty
acid oxidation. In contrast, SIRT3 silencing exacerbated RIP140-induced
cardiomyocyte hypertrophy and mitochondrial dysfunction. Furthermore, the
repression of SIRT3 by RIP140 was dependent on estrogen-related receptor-alpha
(ERRalpha). The involvement of peroxisome proliferator-activated receptor-gamma
coactivator-1alpha (PGC-1alpha) was ruled out of SIRT3 suppression by RIP140.
RIP140 and PGC-1alpha might act as functional antagonists on the regulation of
SIRT3. CONCLUSION: This study indicates that suppression of SIRT3 by RIP140
facilitates the development of cardiomyocyte hypertrophy, mitochondrial
dysfunction and energy metabolic dysfunction. Strategies targeting inhibition of
RIP140 and upregulation of SIRT3 might improve cardiac energy metabolism and
suggest therapeutic potential for heart diseases.
PMID- 27614094
TI - Increasing nest predation will be insufficient to maintain polar bear body
condition in the face of sea ice loss.
AB - Climate change can influence interspecific interactions by differentially
affecting species-specific phenology. In seasonal ice environments, there is
evidence that polar bear predation of Arctic bird eggs is increasing because of
earlier sea ice breakup, which forces polar bears into nearshore terrestrial
environments where Arctic birds are nesting. Because polar bears can consume a
large number of nests before becoming satiated, and because they can swim between
island colonies, they could have dramatic influences on seabird and sea duck
reproductive success. However, it is unclear whether nest foraging can provide an
energetic benefit to polar bear populations, especially given the capacity of
bird populations to redistribute in response to increasing predation pressure. In
this study, we develop a spatially explicit agent-based model of the predator
prey relationship between polar bears and common eiders, a common and culturally
important bird species for northern peoples. Our model is composed of two types
of agents (polar bear agents and common eider hen agents) whose movements and
decision heuristics are based on species-specific bioenergetic and behavioral
ecological principles, and are influenced by historical and extrapolated sea ice
conditions. Our model reproduces empirical findings that polar bear predation of
bird nests is increasing and predicts an accelerating relationship between
advancing ice breakup dates and the number of nests depredated. Despite increases
in nest predation, our model predicts that polar bear body condition during the
ice-free period will continue to decline. Finally, our model predicts that common
eider nests will become more dispersed and will move closer to the mainland in
response to increasing predation, possibly increasing their exposure to land
based predators and influencing the livelihood of local people that collect eider
eggs and down. These results show that predator-prey interactions can have
nonlinear responses to changes in climate and provides important predictions of
ecological change in Arctic ecosystems.
PMID- 27614091
TI - Patterns of CRISPR/Cas9 activity in plants, animals and microbes.
AB - The CRISPR/Cas9 system and related RNA-guided endonucleases can introduce double
strand breaks (DSBs) at specific sites in the genome, allowing the generation of
targeted mutations in one or more genes as well as more complex genomic
rearrangements. Modifications of the canonical CRISPR/Cas9 system from
Streptococcus pyogenes and the introduction of related systems from other
bacteria have increased the diversity of genomic sites that can be targeted,
providing greater control over the resolution of DSBs, the targeting efficiency
(frequency of on-target mutations), the targeting accuracy (likelihood of off
target mutations) and the type of mutations that are induced. Although much is
now known about the principles of CRISPR/Cas9 genome editing, the likelihood of
different outcomes is species-dependent and there have been few comparative
studies looking at the basis of such diversity. Here we critically analyse the
activity of CRISPR/Cas9 and related systems in different plant species and
compare the outcomes in animals and microbes to draw broad conclusions about the
design principles required for effective genome editing in different organisms.
These principles will be important for the commercial development of crops, farm
animals, animal disease models and novel microbial strains using CRISPR/Cas9 and
other genome-editing tools.
PMID- 27614095
TI - Resonant electron capture by aspartame and aspartic acid molecules.
AB - RATIONALE: The processes for dissociative electron capture are the key mechanisms
for decomposition of biomolecules, proteins in particular, under interaction with
low-energy electrons. Molecules of aspartic acid and aspartame, i.e. modified
dipeptides, were studied herein to define the impact of the side functional
groups on peptide chain decomposition in resonant electron-molecular reactions.
METHODS: The processes of formation and decomposition of negative ions of both
aspartame and aspartic acid were studied by mass spectrometry of negative ions
under resonant electron capture. The obtained mass spectra were interpreted under
thermochemical analysis by quantum chemical calculations. RESULTS: Main channels
of negative molecular ions fragmentation were found and characteristic fragment
ions were identified. CONCLUSIONS: The SOON fragment of the side chain in
aspartic acid is shown to play a key role like the carboxyl group in amino acids
and aliphatic oligopeptides. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27614096
TI - Isolated diffusing capacity reduction is a common clinical presentation in
deployed Iraq and Afghanistan veterans with deployment-related environmental
exposures.
AB - Following deployment to Iraq and Afghanistan ("post-9/11"), a spectrum of
respiratory conditions has been reported; however, there are few published
reports of objective physiologic data or later experience of symptoms and
function. To better understand the post-deployment clinical presentation, we
conducted a retrospective review of pulmonary function testing in 143 veterans
referred to our tertiary care clinic for post-deployment health concerns. More
than 75% of our sample had normal lung volumes and spirometry on pulmonary
function testing; however, an isolated reduction in lung diffusing capacity
(DLCO) was observed in 30% of our sample of post-9/11 veterans. An isolated
reduction in DLCO is a rare pattern in primary-care seeking dyspneic patients,
but is commonly associated with underlying pulmonary disease. Post-9/11 veterans
with respiratory complaints and an isolated reduction in DLCO should undergo
further evaluation.
PMID- 27614098
TI - Ethnic differences in the clustering and outcomes of health behaviours during
pregnancy: results from the Born in Bradford cohort.
AB - Background: Pregnancy is a time of optimal motivation for many women to make
positive behavioural changes. We aim to describe pregnant women with similar
patterns of self-reported health behaviours and examine associations with birth
outcomes. Methods: We examined the clustering of multiple health behaviours
during pregnancy in the Born in Bradford cohort, including smoking physical
inactivity, vitamin d supplementation and exposure to second-hand smoke. Latent
class analysis was used to identify groups of individuals with similar patterns
of health behaviours separately for White British (WB) and Pakistani mothers.
Multinomial regression was then used to examine the association between group
membership and birth outcomes, which included preterm birth and mean birthweight.
Results: For WB mothers, offspring of those in the 'Unhealthiest' group had lower
mean birthweight than those in the 'Mostly healthy but inactive' class, although
no association was observed for preterm birth. For Pakistani mothers, group
membership was not associated with birthweight differences, although the odds of
preterm birth was higher in 'Inactive smokers' compared to the 'Mostly healthy
but inactive' group. Conclusions: The use of latent class methods provides
important information about the clustering of health behaviours which can be used
to target population segments requiring behaviour change interventions
considering multiple risk factors. Given the dominant negative association of
smoking with the birth outcomes investigated, latent class groupings of other
health behaviours may not confer additional risk information for these outcomes.
PMID- 27614097
TI - Reduced nicotine content cigarettes and use of alternative nicotine products:
exploratory trial.
AB - AIMS: To compare the use of alternative nicotine products, smoking behavior and
tobacco biomarker exposure in smokers unwilling to quit who were assigned
randomly to normal nicotine content (NNC) cigarettes or very low nicotine content
(VLNC) cigarettes. DESIGN: Randomized, parallel-arm 8-week study with assignment
to VLNC (VLNC 1, n = 53) or NNC (NNC, n = 27) with access to non-cigarette
combusted and non-combusted tobacco/nicotine products or to VLNC with access to
only non-combusted products (VLNC2, n = 56). SETTING: Clinics in Minnesota, USA.
PARTICIPANTS: Smokers uninterested in quitting smoking with a mean [+/- standard
deviation (SD)] age of 44 (+/- 14) years and smoking 16 (+/- seven)
cigarettes/day; 51% female, 72% white. MEASUREMENTS: During the experimental
period, the measures taken included: rate of alternative products used, amount of
and abstinence from combusted tobacco used and tobacco exposure biomarkers.
FINDINGS: There were higher rates of non-combusted alternative tobacco/nicotine
product use in both VLNC conditions versus the NNC condition [rate ratio (RR) =
2.18, 95% confidence interval (CI) = 1.94, 2.46 and RR = 1.64, 95% CI = 1.46,
1.85, respectively] and in VLNC1 versus VLNC2 condition (RR = 1.33, 95% CI =
1.23, 1.44), accompanied by reduced biomarkers of exposure primarily in VLNC2
condition compared to NNC condition (Ps < 0.05). Fewer combusted products were
smoked at almost all visits (Ps <= 0.02) and there were higher rates of
abstinence for both VLNC conditions compared with the NNC condition (VLNC1 versus
NNC: RR = 9.96, 95% CI = 5.01, 19.81; VLNC2 versus NNC: RR = 11.23, 95% CI =
5.74, 21.97). CONCLUSION: The offer of, and instructions to use, reduced nicotine
content cigarettes during an 8-week period led to greater use of alternative
tobacco/nicotine products compared with continued use of normal nicotine
cigarettes and also reductions in smoking rates.
PMID- 27614099
TI - The psychometric properties of the Hopkins Symptom Checklist-10: a Rasch analysis
based on adolescent data from Norway.
AB - BACKGROUND: The Hopkins Symptom Checklist (HSCL-10) is widely used for both
clinical and epidemiological purposes to measure psychological distress among
adolescents and adults. OBJECTIVE: The purpose of this study was to investigate
the psychometric properties of the HSCL-10 among adolescents in Norway using
Rasch analysis. METHODS: The study is based on cross-sectional data from the
Norwegian Youth Health Surveys, conducted by the Norwegian Institute of Public
Health in 2001 and 2009. The target group comprised of 15- to 16-year olds (Grade
10 students) in Hedmark County, Norway. Ten items with four response categories,
intended to measure anxiety and depression, were analysed. The analysis focused
on invariance, including differential item functioning (DIF) across genders and
years of investigations. In addition, the categorization of the items, targeting,
possible multidimensionality and response dependency, was analysed. RESULTS: The
HSCL-10 shows good reliability and on the whole, the items work well. However,
one item, 'Sleeping difficulties', clearly misfit and some items work differently
for boys and girls and between years of investigations. There is also need for a
better targeting of the scale. CONCLUSIONS: The HSCL-10 has the potential to
measure the psychological distress among adolescents but there is a room for
improvement. Further judgement needs to be made as to whether the misfitting item
'Sleeping difficulties' should be removed or retained.
PMID- 27614100
TI - Treatment of allergic children - Where is the progress (for the practicing
allergist)?
AB - For any kind of therapeutic intervention in allergic diseases such as
environmental control, pharmacological, or immunomodulating treatment including
educational programs, children are addressed separately from adults. Health
authorities like the Food and Drug Administration in the United States of America
or the European Medicine Agency in Europe request a specific 'Pediatric
investigational plan' with studies addressing dose-response relationship, safety,
and efficacy for infants, children, and adolescents. During the last 2 years,
promising advances have been reported for the treatment of a variety of allergic
and immunologic disorders. This review summarizes the progress in the treatment
of pediatric asthma and allergic diseases, based on publications of approximately
the last 2.5 years (end of 2013 until May 2016) in and beyond this journal.
Meanwhile, it highlights areas with promising novel therapeutic approaches, which
are likely to change treatment for allergic children in the near future.
PMID- 27614101
TI - Recent climate hiatus revealed dual control by temperature and drought on the
stem growth of Mediterranean Quercus ilex.
AB - A better understanding of stem growth phenology and its climate drivers would
improve projections of the impact of climate change on forest productivity. Under
a Mediterranean climate, tree growth is primarily limited by soil water
availability during summer, but cold temperatures in winter also prevent tree
growth in evergreen forests. In the widespread Mediterranean evergreen tree
species Quercus ilex, the duration of stem growth has been shown to predict
annual stem increment, and to be limited by winter temperatures on the one hand,
and by the summer drought onset on the other hand. We tested how these climatic
controls of Q. ilex growth varied with recent climate change by correlating a 40
year tree ring record and a 30-year annual diameter inventory against winter
temperature, spring precipitation, and simulated growth duration. Our results
showed that growth duration was the best predictor of annual tree growth. We
predicted that recent climate changes have resulted in earlier growth onset (-10
days) due to winter warming and earlier growth cessation (-26 days) due to
earlier drought onset. These climatic trends partly offset one another, as we
observed no significant trend of change in tree growth between 1968 and 2008. A
moving-window correlation analysis revealed that in the past, Q. ilex growth was
only correlated with water availability, but that since the 2000s, growth
suddenly became correlated with winter temperature in addition to spring drought.
This change in the climate-growth correlations matches the start of the recent
atmospheric warming pause also known as the 'climate hiatus'. The duration of
growth of Q. ilex is thus shortened because winter warming has stopped
compensating for increasing drought in the last decade. Decoupled trends in
precipitation and temperature, a neglected aspect of climate change, might reduce
forest productivity through phenological constraints and have more consequences
than climate warming alone.
PMID- 27614102
TI - The rational design of biomimetic skin barrier lipid formulations using
biophysical methods.
AB - OBJECTIVE: The focus of this communication was to study phospholipid-structured
emulsions whose phase behaviour is modified with monoalkyl fatty amphiphiles.
Ideally, these systems would mimic key physical and structural attributes
observed in human stratum corneum (SC) so that they better alleviate xerotic skin
conditions. METHODS: Phosphatidylcholine-structured emulsions were prepared, and
their phase behaviour modified with monoalkyl fatty amphiphiles. The effect of
molecular volume, acyl chain length and head-group interactions was studied using
a combination of physical methods. Water vapour transmission rate (WVTR) was used
as a primary test to assess occlusive character. Changes in the vibrational modes
observed in Fourier transform infrared (FTIR) spectroscopy and bilayer spacing
measured by X-ray diffraction (XRD) were then applied to elucidate the lateral
and lamellar microstructural characteristics in the systems. RESULTS: Water
vapour transmission rate demonstrated that as the phosphatidylcholine acyl chain
length increased from C14, to C18, to C22, there was a corresponding increase in
occlusive character. The addition of monoalkyl fatty amphiphiles such as behenic
acid, behenyl alcohol or cetostearyl alcohol to a base formulation incorporating
dipalmitoyl and distearoylphosphatidylcholine (C18) was seen to further increase
barrier characteristics of the emulsions. FTIR methods used to probe lipid-chain
conformational ordering demonstrated that as phosphatidylcholine acyl chain
lengths increased, there was a corresponding improvement in acyl chain ordering,
with an increase in thermal transition temperatures. The addition of a monoalkyl
fatty amphiphile resulted in conformational order and thermal transition
temperature improvements trending towards those observed in stratum corneum. FTIR
also demonstrated that systems containing behenic acid or behenyl alcohol
exhibited features associated with orthorhombic character. X-ray diffraction data
showed that addition of monoalkyl fatty amphiphile also resulted in thicker
lamellar structures than when those agents are not present. CONCLUSION: The
generalized approach described herein is shown to mechanistically describe the
occlusive character of phospholipid-structured formulations in the presence of
long-chain fatty acids or alcohols and that they exhibit characteristics
mimicking those found in human SC lipids.
PMID- 27614103
TI - Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.
AB - BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) develops from a
complex process, which includes changes in the liver methylome. Betaine plays a
pivotal role in the regulation of methylogenesis. We performed a two-stage case
control study, which included patients with biopsy-proven NAFLD to explore
circulating levels of betaine and its association with the histological spectrum.
We also explored the association between a missense rs1805074, p.Ser646Pro
variant in DMGDH (dimethylglycine dehydrogenase mitochondrial) and NAFLD severity
(n=390). RESULTS: In the discovery phase (n=48), betaine levels were associated
with the disease severity (P=.0030), including liver inflammation (Spearman R:
0.51, P=.001), ballooning degeneration (R: -0.50, P=.01) and fibrosis (R: -0.54,
P=.0008). Betaine levels were significantly decreased in nonalcoholic
steatohepatitis (NASH) in comparison with nonalcoholic fatty liver (NAFL).
Further replication (n=51) showed that betaine levels were associated with
advanced NAFLD (P=.0085), and patients with NASH had a 1.26-fold decrease in
betaine levels compared with those with NAFL. The rs1805074 was significantly
associated with the disease severity (P=.011). CONCLUSION: NAFLD severity is
associated with a state of betaine-insufficiency.
PMID- 27614104
TI - Reporting intraductal carcinoma of the prostate: a plea for greater
standardization.
PMID- 27614105
TI - Bradykinin receptor blockade restores the baroreflex control of renal sympathetic
nerve activity in cisplatin-induced renal failure rats.
AB - AIM: This study investigated the effect of renal bradykinin B1 and B2 receptor
blockade on the high- and low-pressure baroreceptor reflex regulation of renal
sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure.
METHODS: Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior
to study. Following chloralose/urethane anaesthesia, rats were prepared for
measurement of mean arterial pressure (MAP), heart rate and RSNA and received
intrarenal infusions of either Lys-[des-Arg9 , Leu8 ]-bradykinin (LBK), a
bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor
blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to
volume expansion (VE) were obtained. RESULTS: In the control and renal failure
groups, basal MAP (89 +/- 3 vs. 80 +/- 8 mmHg) and RSNA (2.0 +/- 0.3 vs. 1.7 +/-
0.6 MUV.s) were similar but HR was lower in the latter group (331 +/- 8 vs. 396
+/- 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39%
(P < 0.05) lower than the control but was restored to normal values following
intrarenal infusion of BZ, but not LBK. VE had no effect on MAP or HR but reduced
RSNA by some 40% (P < 0.05) in control but not renal failure rats. Intrarenal LBK
infusion in the renal failure rats normalized the VE induced renal sympatho
inhibition whereas BZ only partially restored the response. CONCLUSION: These
findings suggest that pro-inflammatory bradykinin acting at different receptors
within the kidney generates afferent neural signals which impact differentially
within the central nervous system on high- and low-pressure regulation of RSNA.
PMID- 27614106
TI - Genetic analysis of hereditary gingival fibromatosis using whole exome sequencing
and bioinformatics.
AB - OBJECTIVES: Our study aims to identify genetic variants associated with
hereditary gingival fibromatosis (HGF) by applying whole-exome sequencing (WES)
and bioinformatics analyses such as gene set enrichment analysis (GSEA) and
protein functional network study. SUBJECTS AND METHODS: Two affected siblings
whose grandparents and parents have normal gingiva were chosen for our
investigation. Saliva collected from the patients and their parents were used for
WES. GSEA and protein functional network study were performed to find gene groups
in a biological coordination which are associated with HGF. RESULTS: Genetic
variants for homozygotes and compound heterozygotes were analyzed and translated
into 845 genes. The result from protein functional network study showed that
these genetic variants were mainly observed in genes affecting fibronectin as
well as the immune and autoimmune system. Additionally, three mutated genes in
our HGF patients, TMCO1, RIN2, and INSR, were found through human phenotype
ontology (HPO) to have potential to contribute to gingival hyperplasia.
CONCLUSIONS: Genetic analysis of HGF in this study implicated mutations in
fibronectin and the immune system as triggering abnormal gingival fibromatosis.
PMID- 27614107
TI - Identification and characterization of a plastidial phosphatidylglycerophosphate
phosphatase in Arabidopsis thaliana.
AB - Phosphatidylglycerol (PG) is the only phospholipid in the thylakoid membranes of
chloroplasts of plants, and it is also found in extraplastidial membranes
including mitochondria and the endoplasmic reticulum. Previous studies showed
that lack of PG in the pgp1-2 mutant of Arabidopsis deficient in
phosphatidylglycerophosphate (PGP) synthase strongly affects thylakoid biogenesis
and photosynthetic activity. In the present study, the gene encoding the enzyme
for the second step of PG synthesis, PGP phosphatase, was isolated based on
sequence similarity to the yeast GEP4 and Chlamydomonas PGPP1 genes. The
Arabidopsis AtPGPP1 protein localizes to chloroplasts and harbors PGP phosphatase
activity with alkaline pH optimum and divalent cation requirement. Arabidopsis
pgpp1-1 mutant plants contain reduced amounts of chlorophyll, but photosynthetic
quantum yield remains unchanged. The absolute content of plastidial PG (34:4;
total number of acyl carbons:number of double bonds) is reduced by about 1/3,
demonstrating that AtPGPP1 is involved in the synthesis of plastidial PG. PGP
34:3, PGP 34:2 and PGP 34:1 lacking 16:1 accumulate in pgpp1-1, indicating that
the desaturation of 16:0 to 16:1 by the FAD4 desaturase in the chloroplasts only
occurs after PGP dephosphorylation.
PMID- 27614108
TI - A case report of acute fibrinous and organizing pneumonia with pneumothorax and
avian exposure history.
AB - Acute fibrinous and organizing pneumonia (AFOP) is an uncommon variant of acute
lung injury. Here, we report a patient with AFOP and a previously unreported
condition, pneumothorax. After our experience with this case, we suggest that
exposure to birds may be associated with AFOP; pneumothorax can develop in
patients with AFOP; and glucocorticoids are very effective for treating AFOP.
PMID- 27614109
TI - Impact of laws restricting the sale of tobacco to minors on adolescent smoking
and perceived obtainability of cigarettes: an intervention-control pre-post study
of 19 European Union countries.
AB - AIMS: To estimate the impact of introducing sales restriction laws in Europe by
measuring changes in adolescent smoking prevalence and perceived obtainability of
cigarettes over time in countries that have recently introduced sales restriction
laws (intervention countries). These countries were compared with countries where
such laws were already in force (control countries). The secondary aim was to
test whether these trends differed between adolescents of higher and lower socio
economic position (SEP). DESIGN: Repeated cross-sectional data were used in a
quasi-experimental pre-post design. Intervention countries raised tobacco sales
restrictions to 18 years in 2007, 2008 or 2009. Control countries have had sales
restrictions of 18 years since at least 2004. SETTING: Nineteen European Union
(EU) countries in 2007 and 2011. PARTICIPANTS: Data of 97 245 15- and 16-year-old
adolescents from the 2007 and 2011 European Survey Project on Alcohol and other
Drugs (ESPAD) surveys. MEASUREMENTS: Dependent variables were smoking status
(weekly smoking versus non-smoking or less than weekly smoking) and perceived
obtainability of tobacco (easy versus difficult). Key independent variables were
time (2007 or 2011), intervention exposure (intervention or control country) and
their interaction (time * intervention). Covariates included sex, SEP, the
tobacco control scale (TCS), gross domestic product (GDP) and adult smoking
prevalence. FINDINGS: We did not find a difference in the change in smoking
prevalence between intervention and control countries [odds ratio (OR) = 1.00,
95% confidence interval (CI) = 0.93-1.07]. However, sales restrictions were
associated with a significantly greater decrease in perceived ease of cigarette
obtainability in intervention countries (OR = 0.75, 95% CI = 0.70-0.80). No
significant differential effects between high and low SEP adolescents were found
(OR = 1.01, 95% CI = 0.81-1.25). CONCLUSION: Laws prohibiting the sales of
tobacco to minors in Europe do not appear to be associated with a reduction in
adolescent smoking rates, but lower the perceived obtainability of cigarettes
irrespective of their socio-economic position.
PMID- 27614110
TI - Relationships between estimated flame retardant emissions and levels in indoor
air and house dust.
AB - A significant number of consumer goods and building materials can act as emission
sources of flame retardants (FRs) in the indoor environment. We investigate the
relationship between the emission source strength and the levels of 19 brominated
flame retardants (BFRs) and seven organophosphate flame retardants (OPFRs) in air
and dust collected in 38 indoor microenvironments in Norway. We use modeling
methods to back-calculate emission rates from indoor air and dust measurements
and identify possible indications of an emission-to-dust pathway. Experimentally
based emission estimates provide a satisfactory indication of the relative
emission strength of indoor sources. Modeling results indicate an up to two
orders of magnitude enhanced emission strength for OPFRs (median emission rates
of 0.083 and 0.41 MUg h-1 for air-based and dust-based estimates) compared to
BFRs (0.52 and 0.37 ng h-1 median emission rates). A consistent emission-to-dust
signal, defined as higher dust-based than air-based emission estimates, was
identified for four of the seven OPFRs, but only for one of the 19 BFRs. It is
concluded, however, that uncertainty in model input parameters could potentially
lead to the false identification of an emission-to-dust signal.
PMID- 27614111
TI - Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy
of ramipril and hydrochlorothiazide.
AB - We present a dendrimer-based hybrid formulation strategy to explore the potential
of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination
therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic
hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase
equilibration method. The results showed that the solubility of RAPL and HCTZ was
dependent on dendrimer concentration and pH of dendrimer solution. The solubility
profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear
relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration,
solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ,
solubility enhancement was highest (3.72 folds) with carboxy-terminated. The
complexes were characterized by Fourier transform infrared spectroscopy, nuclear
magnetic resonance analysis and high performance liquid chromatography. In-vitro
drug dissolution performance of pure drugs, individual drug loaded dendrimer
formulations and hybrid formulations was studied in USP dissolution medium
(pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations
showed faster and complete dissolution compared to pure RAPL or HCTZ.
Surprisingly, similar pattern of dissolution profile was established with hybrid
formulations as compared to individual drug loaded dendrimers. The dendrimer
based hybrid formulations were found to be stable at dark and refrigerated
conditions up to 5weeks. Conclusively, the proposed formulation strategy
establishes a novel multitasking platform using dendrimer for simultaneous
loading and delivery of multiple drugs for pharmaceutical applications.
PMID- 27614112
TI - The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the
expression of genes involved in Abeta generation.
AB - The receptor interacting protein-140 (RIP140) is a cofactor for several nuclear
receptors and has been involved in the regulation of metabolic and inflammatory
genes. We hypothesize that RIP140 may also affect Abeta generation because it
modulates the activity of transcription factors previously implicated in amyloid
precursor protein (APP) processing, such as peroxisome proliferator-activated
receptor-gamma (PPARgamma). We found that the levels of RIP140 are reduced in
Alzheimer's disease (AD) postmortem brains compared with healthy controls. In
addition, in situ hybridization experiments revealed that RIP140 expression is
enriched in the same brain areas involved in AD pathology, such as cortex and
hippocampus. Furthermore, we provide evidence using cell lines and genetically
modified mice that RIP140 is able to modulate the transcription of certain genes
involved in AD pathology, such as beta-APP cleaving enzyme (BACE1) and GSK3.
Consequently, we found that RIP140 overexpression reduced the generation of Abeta
in a neuroblastoma cell line by decreasing the transcription of beta-APP cleaving
enzyme via a PPARgamma-dependent mechanism. The results of this study therefore
provide molecular insights into common signaling pathways linking metabolic
disease with AD.
PMID- 27614113
TI - Distribution of human umbilical cord blood-derived mesenchymal stem cells (hUCB
MSCs) in canines after intracerebroventricular injection.
AB - In this study, we investigated the distribution of human umbilical cord blood
derived mesenchymal stem cells (hUCB-MSCs) administered via
intracerebroventricular (ICV) injection in a canine model. Ten beagles (11-13 kg
per beagle) each received an injection of 1 * 106 cells into the right lateral
ventricle and were sacrificed 7 days after administration. Based on
immunohistochemical analysis, hUCB-MSCs were observed in the brain parenchyma,
especially along the lateral ventricular walls. Detected as far as 3.5 mm from
the cortical surface, these cells migrated from the lateral ventricle toward the
cortex. We also observed hUCB-MSCs in the hippocampus and the cervical spinal
cord. According to real-time polymerase chain reaction results, most of the hUCB
MSCs were found distributed in the brain and the cervical spinal cord but not in
the lungs, heart, kidneys, spleen, and liver. ICV administered hUCB-MSCs also
enhanced the endogenous neural stem cell population in the subventricular zone.
These results highlighted the ICV delivery route as an optimal route to be
performed in stem cell-based clinical therapies for neurodegenerative diseases.
PMID- 27614115
TI - Esophageal atresia with tracheoesophageal fistula in a patient with 7q35-36.3
deletion including SHH gene.
AB - Terminal 7q deletion is rarely reported in the literature. Holoprosencephaly and
sacral dysgenesis are found in association with this deletion, due to
haploinsufficiency of SHH and HLBX9 genes respectively. We report on a 2-year-old
boy with 7q35-36.3 deletion encompassing SHH identified by oligonucleotide array
comparative genomic hybridization. In addition to other frequent features, the
patient presented with esophageal atresia and tracheoeosophageal fistula
diagnosed at birth. This case, together with two others previously described, one
presenting with esophageal atresia, the other with congenital esophageal
stenosis, confirms the possible association between congenital esophageal
malformations and 7q terminal deletion including SHH.
PMID- 27614116
TI - The effect of dental bleaching on pulpal tissue response in a diabetic animal
model.
AB - AIM: To evaluate pulpal tissue response after dental bleaching in normal and
alloxan-induced diabetic rats. METHODOLOGY: Twenty-eight rats were divided into
two groups of normoglycaemic and diabetic rats (n = 14). Diabetes mellitus (DM)
was induced with alloxan. After DM confirmation, all rats were anaesthetized and
dental bleaching was performed with 35% hydrogen peroxide (H2 O2 ) on the right
maxillary molars for 30 min. Left molars were used as controls. Bleaching
resulted in four hemimaxillae groups: normoglycaemic (N), N-bleached (NBle),
diabetic (D) and D-bleached (DBle). After 2 or 30 days, the animals were
euthanized and the hemimaxillae were removed, processed for histopathological
analysis and stained with haematoxylin-eosin (HE), Masson's trichrome (MT) and
picrosirius red (PSR). Results obtained within animals (normoglycaemic or
diabetic rats) were submitted to Wilcoxon or paired t-tests, and between animal
(normoglycaemic and diabetic rats), to Mann-Whitney test or t-tests. RESULTS: At
2 days, the NBle group had a mild inflammatory infiltration in the pulpal tissue,
whilst the DBle had severe inflammation or necrosis (P < 0.05). At 30 days, no
inflammation was present. However, a significant difference in pulp chamber area
reduction by reactionary dentine deposition was found between the NBle and DBle
groups (P < 0.05). At 2 days, fewer immature collagen fibres and more mature
collagen fibres were noted in the NBle, D and DBle groups; this was significantly
different when compared to the N group (P < 0.05). At 30 days, significantly
fewer immature collagen fibres and more mature collagen fibres were noted in NBle
compared with DBle group (P < 0.05). CONCLUSIONS: The inflammatory tissue
response in rats' teeth after dental bleaching was greater in diabetic rats.
Additionally, the increase in reactionary dentine deposition and mature collagen
fibres observed in diabetic rats needs further evaluation to confirm the present
results.
PMID- 27614117
TI - Do the energy fluxes and surface conductance of boreal coniferous forests in
Europe scale with leaf area?
AB - Earth observing systems are now routinely used to infer leaf area index (LAI)
given its significance in spatial aggregation of land surface fluxes. Whether LAI
is an appropriate scaling parameter for daytime growing season energy budget,
surface conductance (Gs ), water- and light-use efficiency and surface-atmosphere
coupling of European boreal coniferous forests was explored using eddy-covariance
(EC) energy and CO2 fluxes. The observed scaling relations were then explained
using a biophysical multilayer soil-vegetation-atmosphere transfer model as well
as by a bulk Gs representation. The LAI variations significantly alter radiation
regime, within-canopy microclimate, sink/source distributions of CO2 , H2 O and
heat, and forest floor fluxes. The contribution of forest floor to ecosystem
scale energy exchange is shown to decrease asymptotically with increased LAI, as
expected. Compared with other energy budget components, dry-canopy
evapotranspiration (ET) was reasonably 'conservative' over the studied LAI range
0.5-7.0 m2 m-2 . Both ET and Gs experienced a minimum in the LAI range 1-2 m2 m-2
caused by opposing nonproportional response of stomatally controlled
transpiration and 'free' forest floor evaporation to changes in canopy density.
The young forests had strongest coupling with the atmosphere while stomatal
control of energy partitioning was strongest in relatively sparse (LAI ~2 m2 m-2
) pine stands growing on mineral soils. The data analysis and model results
suggest that LAI may be an effective scaling parameter for net radiation and its
partitioning but only in sparse stands (LAI <3 m2 m-2 ). This finding emphasizes
the significance of stand-replacing disturbances on the controls of surface
energy exchange. In denser forests, any LAI dependency varies with physiological
traits such as light-saturated water-use efficiency. The results suggest that
incorporating species traits and site conditions are necessary when LAI is used
in upscaling energy exchanges of boreal coniferous forests.
PMID- 27614114
TI - Widespread white matter and conduction defects in PSEN1-related spastic
paraparesis.
AB - The mechanisms underlying presenilin 1 (PSEN1) mutation-associated spastic
paraparesis (SP) are not clear. We compared diffusion and volumetric magnetic
resonance measures between 3 persons with SP associated with the A431E mutation
and 7 symptomatic persons with PSEN1 mutations without SP matched for symptom
duration. We performed amyloid imaging and central motor and somatosensory
conduction studies in 1 subject with SP. We found decreases in fractional
anisotropy and increases in mean diffusivity in widespread white-matter areas
including the corpus callosum, occipital, parietal, and frontal lobes in PSEN1
mutation carriers with SP. Volumetric measures were not different, and amyloid
imaging showed low signal in sensorimotor cortex and other areas in a single
subject with SP. Electrophysiological studies demonstrated both slowed motor and
sensory conduction in the lower extremities in this same subject. Our results
suggest that SP in carriers of the A431E PSEN1 mutation is a manifestation of
widespread white-matter abnormalities not confined to the corticospinal tract
that is at most indirectly related to the mutation's effect on amyloid precursor
protein processing and amyloid deposition.
PMID- 27614118
TI - Novel Surgical Approach to Giant Abdominoscrotal Hydrocele-Video.
AB - Repair of abdominoscrotal hydrocele is surgically demanding and may be associated
with complications. Herein we describe a surgical technique with laparoscopic
assisted approach. A 6-month boy with right hydrocele and left absent testis was
surgically treated with scrotal approach using one laparoscopic port. In the
presence of abdominoscrotal hydrocele and contralateral absent testis, we opted
to correct the hydrocele while minimally mobilizing the solitary testis cord and
blood vessels. The patient had minimal drainage-postoperatively, he developed
fever and was treated with antibiotics. Abdominoscrotal hydrocele in infancy may
simply and successfully be treated via scrotal approach with the assistance of
one-port laparoscopy (Video).
PMID- 27614119
TI - Urological Findings in Beckwith-Wiedemann Syndrome With Chromosomal Duplications
of 11p15.5: Evaluation and Management.
AB - Beckwith-Wiedemann Syndrome (BWS) is an overgrowth disorder with various
congenital anomalies. Although the most classic constellation includes
macrosomia, macroglossia, and omphalocele, nephrourological findings are commonly
associated with BWS. Clinical presentation is highly variable because of its
complex molecular heterogeneity, which involves changes in DNA methylation and
disruption of growth regulatory genes. We report 3 pediatric patients, ages 13
months to 3 years old, who presented with clinical features consistent with BWS.
A variety of nephrourological abnormalities were also noted, including posterior
urethral valves, hydroureteronephrosis, and undescended testes. Genetic testing
for all 3 patients revealed duplication of the region chromosome 11p15.5.
PMID- 27614120
TI - Functional Implications of Renal Tumor Enucleation Relative to Standard Partial
Nephrectomy.
AB - OBJECTIVE: To compare the surgical precision for optimizing nephron-mass
preservation of tumor enucleation (TE) vs standard partial nephrectomy (SPN),
with primary focus on functional outcomes. TE is presumed to optimize
preservation of parenchymal mass and function but this has not yet been
rigorously studied and quantified. MATERIALS AND METHODS: Robotic partial
nephrectomy patients who had appropriate pre- and postoperative studies for
analysis of parenchymal mass preservation specific to the operated kidney were
included. Computed tomography or magnetic resonance imaging and estimated
glomerular filtration rate were required to be <2 months prior and 4-12 months
after surgery. Parenchymal mass preservation and surgical precision were
estimated for each technique, with precision defined as actual postoperative
parenchymal volume or predicted postoperative parenchymal volume, presuming loss
of a 5 mm rim of parenchyma associated with tumor excision and reconstruction.
RESULTS: Analysis included 57 TE and 53 SPN. Median age, body mass index, and
tumor size were comparable. Percent parenchymal mass preserved in the operated
kidney with TE was 96% (interquartile range [IQR] = 90-100) vs 89% (IQR = 83-96)
for SPN (P = .003). Precision of excision or reconstruction was 101% (IQR = 96
105) for TE vs 94% (IQR = 88-100) for SPN (P < .001). On multivariable analysis,
only TE correlated with improved surgical precision (coefficient = 6.7, 95%
confidence interval = 1.6-11.8, P = .01). Although preservation of global renal
function also favored TE, the differences were marginal (96% vs 93%), and
statistical significance was not observed (P = .2). CONCLUSION: Our analysis,
which specifically focuses on the functional implications of TE, demonstrates
that TE maximally spares normal parenchyma compared to SPN. Thus far, functional
differences remain marginal and not statistically significant. Clinical
significance of these findings in various clinical settings will require further
investigation.
PMID- 27614121
TI - Management of Renal Artery Occlusion Related to Multiple Trauma in Children: Two
Case Reports.
AB - We report 2 successful treatment cases of renal artery occlusion (RAO) related to
multiple trauma. A 4-year-old boy was diagnosed with right RAO and liver
laceration after a traffic accident. Surgical thrombectomy and revascularization
were performed, but the lacerated liver was not sutured. The lacerated liver was
surgically repaired 6 days post operation because of delayed bleeding. Thirteen
percent of the patient's right kidney function was conserved. Another 7-year-old
boy was compressed by an agitator. Renal scintigraphy showed that the right
kidney was nonfunctional. The patient underwent conservative observation without
any complication. In stable patients with multiple trauma, RAO should be
diagnosed as soon as possible.
PMID- 27614123
TI - Insufficient evidence on the association between light alcohol drinking and the
risk of cancer: On the need for correction of the newly revised European Code
against Cancer 4th edition.
PMID- 27614122
TI - Fermentation of African kale (Brassica carinata) using L. plantarum BFE 5092 and
L. fermentum BFE 6620 starter strains.
AB - Vegetables produced in Africa are sources of much needed micronutrients and
fermentation is one way to enhance the shelf life of these perishable products.
To prevent post-harvest losses and preserve African leafy vegetables,
Lactobacillus plantarum BFE 5092 and Lactobacillus fermentum BFE 6620 starter
strains were investigated for their application in fermentation of African kale
(Brassica carinata) leaves. They were inoculated at 1*107cfu/ml and grew to a
maximum level of 108cfu/ml during 24h submerged fermentation. The strains
utilized simple sugars (i.e., glucose, fructose, and sucrose) in the kale to
quickly reduce the pH from pH6.0 to pH3.6 within 24h. The strains continued to
produce both d and l lactic acid up to 144h, reaching a maximum concentration of
4.0g/l. Fermentations with pathogens inoculated at 104cfu/ml showed that the
quick growth of the starters inhibited the growth of Listeria monocytogenes and
Salmonella Enteritidis, as well as other enterobacteria. Denaturing gradient gel
electrophoresis and 16S rRNA gene (V3-V4-region) amplicon sequencing showed that
in the spontaneous fermentations a microbial succession took place, though with
marked differences in biodiversity from fermentation to fermentation. The
fermentations inoculated with starters however were clearly dominated by both the
inoculated strains throughout the fermentations. RAPD-PCR fingerprinting showed
that the strains established themselves at approx. equal proportions. Although
vitamins C, B1 and B2 decreased during the fermentation, the final level of
vitamin C in the product was an appreciable concentration of 35mg/100g. In
conclusion, controlled fermentation of kale offers a promising avenue to prevent
spoilage and improve the shelf life and safety.
PMID- 27614124
TI - To evaluate of the effect of adding licorice to the standard treatment regimen of
Helicobacter pylori.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of licorice in H.
pylori eradication in patients suffering from dyspepsia either with peptic ulcer
disease (PUD) or non-ulcer dyspepsia (NUD) in comparison to the clarithromycin
based standard triple regimen. METHODS: In this randomized controlled clinical
trial, 120 patients who had positive rapid urease test were included and assigned
to two treatment groups: control group that received a clarithromycin-based
triple regimen, and study group that received licorice in addition to the
clarithromycin-based regimen for two weeks. H. pylori eradication was assessed
six weeks after therapy. Data was analyzed by chi-square and t-test with SPSS 16
software. RESULTS: Mean ages and SD were 38.8+/-10.9 and 40.1+/-10.4 for the
study and control groups, respectively, statistically similar. Peptic ulcer was
found in 30% of both groups. Response to treatment was 83.3% and 62.5% in the
study and control groups, respectively. This difference was statistically
significant. CONCLUSION: Addition of licorice to the triple clarithromycin-based
regimen increases H. pylori eradication, especially in the presence of peptic
ulcer disease.
PMID- 27614125
TI - Traumatic brain injury induced matrix metalloproteinase2 cleaves CXCL12alpha
(stromal cell derived factor 1alpha) and causes neurodegeneration.
AB - Traumatic brain injury (TBI), even at mild levels, can activate matrix
metalloproteinases (MMPs) and the induction of neuroinflammation that can result
in blood brain barrier breakdown and neurodegeneration. MMP2 has a significant
role in neuroinflammation and neurodegeneration by modulating the chemokine
CXCL12alpha (stromal cell derived factor SDF-1alpha) signaling pathway and the
induction of apoptosis. SDF-1alpha is responsible for cell proliferation and
differentiation throughout the nervous system and is also implicated in various
neurodegenerative illnesses. We hypothesized that TBI leads to MMP2 activation
and cleavage of the N-terminal 4 amino acid residues of CXCL12alpha with
generation of the highly neurotoxic fragment SDF-1(5-67). Using an in vitro
stretch-injury model of rat neuronal cultures and the in vivo fluid percussion
injury (FPI) model in rats, we found that oxidative stress has a significant role
in the activation of MMP2. This is initiated by the induction of free radical
generating enzyme NADPH oxidase 1 (NOX1). Induction of NOX1 correlated well with
the signatures of oxidative stress marker, 4HNE in the injured neuronal cultures
and cerebral cortex of rats. Further, using MMP2 siRNA and pharmacological MMP2
inhibitor, ARP100, we established the neurodegenerative role of MMP2 in cleaving
SDF-1alpha to a neurotoxic fragment SDF-1(5-67). By immunofluorescence, western
blotting and TUNEL experiments, we show the cleaved form of SDF leads to
apoptotic cell death in neurons. This work identifies a new potential therapeutic
target to reduce the complications of brain damage in TBI.
PMID- 27614126
TI - Protective role of 6-Hydroxy-1-H-Indazole in an MPTP-induced mouse model of
Parkinson's disease.
AB - This study aimed to explore the neuroprotective role of 6-hydroxy-1H-indazole on
dopaminergic neurons in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)
mouse model of Parkinson's disease (PD). Forty 12-week-old C57BL/6 male mice were
were randomized divided into 4 groups. Mice were treated with 2mg/kg and 4mg/kg 6
hydroxy-1H-indazole (i.p.) 1d before the initiation of MPTP administration
(30mg/kg), and the 6-hydroxy-1H-indazole were daily injected half an hour before
MPTP treatment in the following 5 days. The MPTP group was given normal saline on
day 1 (i.p.), followed by 30mg/kg MPTP treatment in the following 5 days. Control
group received an equivalent volume of normal saline. Ten days after the final
injection of MPTP, the mice were killed. The results showed that MPTP decreased
the dopaminergic neurons in the substantia nigra and dopamine in the striatum,
downregulated the expression of tyrosine hydroxylase (TH), induced the impairment
of behavior and hyperphosphorylation of tau, However, 6-hydroxy-1-H-indazole
decreased the loss of dopaminergic neurons, increased dopamine concentration and
TH expression, alleviated the behavioral damage and level of phosphor-tau in the
MPTP-induced model of PD in C57BL/6 mice. These findings showed that 6-hydroxy-1
H-indazole-mediated neuroprotection was related to the inactivation of tau. In
addition, 6-hydroxy-1-H-indazole may be a potential drug candidate for PD.
PMID- 27614127
TI - Salvianolic acid B improves vascular endothelial function in diabetic rats with
blood glucose fluctuations via suppression of endothelial cell apoptosis.
AB - Vascular endothelial cell injury is an initial event in atherosclerosis.
Salvianolic acid B (Sal B), a main bioactive component in the root of Salvia
miltiorrhiza, has vascular protective effect in diabetes, but the underlying
mechanisms remain unclear. The present study investigated the effect of Sal B on
vascular endothelial function in diabetic rats with blood glucose fluctuations
and the possible mechanisms implicated. The results showed that diabetic rats
developed marked endothelial dysfunction as exhibited by impaired acetylcholine
induced vasodilation. Supplementation with Sal B resulted in an evident
improvement of endothelial function. Phosphorylation (Ser 1177) of endothelial
nitric oxide synthase (eNOS) was significantly restored in Sal B treated diabetic
rats, accompanied by an evident recovery of NO metabolites. Sal B effectively
reduced vascular endothelial cell apoptosis, with Bcl-2 protein up-regulated and
Bax protein down-regulated markedly. Treatment with Sal B led to an evident
amelioration of oxidative stress in diabetic rats as manifested by enhanced
antioxidant capacity and decreased contents of malondialdehyde in aortas. Protein
levels of NOX2 and NOX4, two main isoforms of NADPH oxidase known as the major
source of reactive oxygen species in the vasculature, were markedly decreased in
Sal B treated groups. In addition, treatment with Sal B led to an evident
decrease of serum lipids. Taken together, this study indicates that Sal B is
capable of improving endothelial function in diabetic rats with blood glucose
fluctuations, of which the underlying mechanisms might be related to suppression
of endothelial cell apoptosis and stimulation of eNOS phosphorylation (Ser 1177).
PMID- 27614128
TI - Pioglitazone inhibits EGFR/MDM2 signaling-mediated PPARgamma degradation.
AB - Aberrant activation of the epidermal growth factor receptor (EGFR) signaling is
involved in many cancer events. Although peroxisome proliferator-activated
receptor gamma (PPARgamma) has been implicated in inhibition of inflammation and
cancer, EGFR/MDM2 signaling induces PPARgamma phosphorylation and degradation.
Here we found that cancer cells in response to EGF reduced PPARgamma protein
levels by inducing its phosphorylation, ubiquitination and degradation, but
PPARgamma agonist pioglitazone reversed this event. More importantly,
pioglitazone increased cancer cell sensitivity to chemotherapy drugs. Therefore,
our study revealed a novel mechanism that pioglitazone inhibited EGFR/MDM2
mediated cancer cell chemoresistance, which provides a novel strategy for cancer
treatment.
PMID- 27614129
TI - Small molecules exert anti-apoptotic effect and reduce oxidative stress
augmenting insulin secretion in stem cells engineered islets against hypoxia.
AB - Transplantation of pancreatic islets is the most reliable treatment for Type 1
diabetes. However cell death mediated by hypoxia is considered as one of the main
difficulties hindering success in islet transplantation. The aim of our
experiment was to investigate the role of small molecules in survival of Islet
like cell aggregates (ICAs) engineered from umbilical cord matrix under oxygen
deprived condition (<5% O2). ICAs were analyzed for cell death via fluoroscein
diacetate/propidium iodide (FDA/PI) staining, estimation of Caspase 3 and free
radical release in presence and absence of small molecules. The samples were also
analyzed for the presence of hypoxia inducible factor 1alpha (HIF1alpha) at both
transcriptional and translational level. The addition of small molecules showed
profound defensive effect on ICAs under hypoxic environment as evidenced by their
viability and insulin secretion compared to untreated ICAs. The combinations of
Eicosapentaenoic acid (EPA), Docosahexaenoic acid(DHA) and metformin and EPA,
DHAandgamma amino butyric acid (GABA) acted as anti-apoptotic agents for human
ICAs when exposed to 1% O2 for 48h. The combinations of the small molecules
reduced the total reactive oxygen species and malonaldehyde (MDA) levels and
enhanced the production of glutathione peroxidise (GPx) enzyme under hypoxic
conditions. Finally the increase in HIF1alpha at both protein and gene level
confirmed the defensive effect of the additives in hypoxia. These results suggest
that the combination of small molecules maintained the viability and
functionality of the ICAs in hypoxia by up-regulating HIF1alpha expression and
down regulating the Caspase 3 activity.
PMID- 27614130
TI - Central inhibitory effects on feeding induced by the adipo-myokine irisin.
AB - Irisin, the soluble secreted form of fibronectin type III domain containing 5
(FNDC5)-cleaved product, is a recently identified adipo-myokine that has been
indicated as a possible link between physical exercise and energetic homeostasis.
The co-localization of irisin with neuropeptide Y in hypothalamic sections of
paraventricular nucleus, which receives NPY/AgRP projections from the arcuate
nucleus, suggests a possible role of irisin in the central regulation of energy
balance. In this context, in the present work we studied the effects of intra
hypothalamic irisin (1MUl, 50-200nmol/l) administration on feeding and orexigenic
[agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and
anorexigenic [cocaine and amphetamine-regulated transcript (CART) and
proopiomelanocortin (POMC)] peptides in male Sprague-Dawley rats. Furthermore, we
evaluated the effects of irisin on hypothalamic dopamine (DA), norepinephrine
(NE) and serotonin (5-hydroxytryptamine, 5-HT) concentrations and plasma NE
levels. Compared to vehicle, irisin injected rats showed decreased food intake,
possibly mediated by stimulated CART and POMC and inhibited DA, NE and orexin-A,
in the hypothalamus. We also found increased plasma NE levels, supporting a role
for sympathetic nervous system stimulation in mediating increased oxygen
consumption by irisin.
PMID- 27614133
TI - Retraction notice to "A neutralizing scFv antibody against infectious bursal
disease virus screened by flow cytometry" [JIM 424 (2015) 80 - 84].
PMID- 27614131
TI - Intracellular zinc status influences cisplatin-induced endothelial permeability
through modulation of PKCalpha, NF-kappaB and ICAM-1 expression.
AB - Platinum-based chemotherapeutic regimen induces vascular dysfunction. Action of
cisplatin on endothelial cells is mediated by protein kinase C (PKC-alpha), which
further activates nuclear factor-kappaB (NF-kappaB) and induces canonical
transient receptor potential channel (TRPC1) and intercellular adhesion molecule
(ICAM-1) expression. Increased ICAM-1 contributes to hyperadhesion of monocytes
and endothelial dysfunction. PKC-alpha is also involved in phosphorylation of
TRPC1, resulting in store-operated calcium entry (SOCE) and further activation of
NF-kappaB. Although the role of altered intracellular zinc status is not known in
cisplatin-induced vascular dysfunction, because of the ability of zinc to
modulate PKC-alpha, NF-kappaB activity, we hypothesized that zinc can ameliorate
the extent of endothelial dysfunction induced by cisplatin. Human umbilical vein
endothelial cells treated with cisplatin (8.0MUg/ml) showed lowered intracellular
free zinc, concomitant with enhanced activation of PKC-alpha, NF-kappaBeta
activation, TRPC1, SOCE and ICAM-1 levels. Zinc deficiency per se induced using
membrane permeable chelator (TPEN) mimicked the cisplatin-induced PKC-alpha, NF
kappaB activation and ICAM-1 expression, but also activated Activator Protein-1
(AP-1). Zinc supplementation (2.0-10.0MUM) to the endothelial cells during
cisplatin treatment or TPEN-induced zinc deficiency suppressed PKC-alpha, NF
kappaB, TRPC1, SOCE activation and lowered the ICAM-1 expression. Zinc
supplementation thereby effectively decreased the cisplatin-induced endothelial
permeability and adherence of the activated endothelial cells to U937 monocytes.
PMID- 27614132
TI - The adipose tissue of origin influences the biological potential of human adipose
stromal cells isolated from mediastinal and subcutaneous fat depots.
AB - Indirect evidence suggests that adipose tissue-derived stromal cells (ASCs)
possess different physiological and biological variations related to the
anatomical localization of the adipose depots. Accordingly, to investigate the
influence of the tissue origin on the intrinsic properties of ASCs and to assess
their response to specific stimuli, we compared the biological, functional and
ultrastructural properties of two ASC pools derived from mediastinal and
subcutaneous depots (thoracic compartment) by means of supplements such as
platelet lysate (PL) and FBS. Subcutaneous ASCs exhibited higher proliferative
and clonogenic abilities than mediastinal counterpart, as well as increased
secreted levels of IL-6 combined with lower amount of VEGF-C. In contrast,
mediastinal ASCs displayed enhanced pro-angiogenic and adipogenic differentiation
properties, increased cell diameter and early autophagic processes, highlighted
by electron microscopy. Our results further support the hypothesis that the
origin of adipose tissue significantly defines the biological properties of ASCs,
and that a homogeneric function for all ASCs cannot be assumed.
PMID- 27614135
TI - Corrigendum to "Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology
assessment in support of human and mammalian safety" [Regul. Toxicol. Pharmacol.
81 (2016) 57-68].
PMID- 27614134
TI - Role of the mitochondrial contact site and cristae organizing system in membrane
architecture and dynamics.
AB - The elaborate membrane architecture of mitochondria is a prerequisite for
efficient respiration and ATP generation. The cristae membranes, invaginations of
the inner mitochondrial membrane, represent a specialized compartment that
harbors the complexes of the respiratory chain and the F1Fo-ATP synthase. Crista
junctions form narrow openings that connect the cristae membranes to the inner
boundary membrane. The mitochondrial contact site and cristae organizing system
(MICOS) is located at crista junctions where it stabilizes membrane curvature and
forms contact sites between the mitochondrial inner and outer membranes. MICOS is
a large machinery, consisting of two dynamic subcomplexes that are anchored in
the inner membrane and expose domains to the intermembrane space. The functions
of MICOS in mitochondrial membrane architecture and biogenesis are influenced by
numerous interaction partners and the phospholipid environment.
PMID- 27614136
TI - Authors' response to Lewandowski and Cohen.
PMID- 27614137
TI - Prediction of carcinogenic potential of chemicals using repeated-dose (13-week)
toxicity data.
AB - Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in
order to predict the tumour outcome of 24-month rat carcinogenicity studies
obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals
that did not induce putative preneoplastic lesions in the sub-chronic study also
did not induce tumours in the carcinogenicity study (True Negatives). Cellular
hypertrophy appeared to be an unreliable predictor of carcinogenicity. The
negative predictivity, the measure of the compounds evaluated that did not show
any putative preneoplastic lesion in de sub-chronic studies and were negative in
the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the
sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The
specificity, the accuracy of the sub-chronic study to correctly identify non
carcinogens was 90%. When the chemicals which induced tumours generally
considered not relevant for humans (33 out of 37 False Negatives) are classified
as True Negatives, the negative predictivity amounts to 97%. Overall, the results
of this retrospective study support the concept that chemicals showing no
histopathological risk factors for neoplasia in a sub-chronic study in rats may
be considered non-carcinogenic and do not require further testing in a
carcinogenicity study.
PMID- 27614138
TI - Age-related differences in brain activity during implicit and explicit processing
of fearful facial expressions.
AB - Age-related differences in neural correlates underlying implicit and explicit
emotion processing are unclear. Within the framework of the Frontoamygdalar Age
related Differences in Emotion model (St Jacques et al., 2009), our objectives
were to examine the behavioral and neural modifications that occur with age for
both processes. During explicit and implicit processing of fearful faces, we
expected to observe less amygdala activity in older adults (OA) than in younger
adults (YA), associated with poorer recognition performance in the explicit task,
and more frontal activity during implicit processing, suggesting compensation. At
a behavioral level, explicit recognition of fearful faces was impaired in OA
compared with YA. We did not observe any cerebral differences between OA and YA
during the implicit task, whereas in the explicit task, OA recruited more
frontal, parietal, temporal, occipital, and cingulate areas. Our findings suggest
that automatic processing of emotion may be preserved during aging, whereas
deliberate processing is impaired. Additional neural recruitment in OA did not
appear to compensate for their behavioral deficits.
PMID- 27614139
TI - AMPA receptor trafficking in recent vs. remote memory.
AB - : It is now established that iteration of memory circuits takes place from
hippocampus to cortical regions. The recall of recent event is largely dependent
on the hippocampus networks, however, with passage of time, the cortical regions
become largely involved in the recall of remote events. Molecular events,
specifically, the AMPA receptor regulation underlying this iteration remains
largely elusive. METHOD: Separate groups of mice were fear conditioned using
contextual fear conditioning paradigm. Memory retrieval test was performed 1 day
post-training, for the recent memory group, together with respective controls.
Where as, in case of remote group retrieval was performed 30 days post training.
One hour post retrieval session, hippocampus and anterior cingulate regions were
harvested after decapitation from all the groups, which were processed for
synaptic membrane isolation and quantitative western blotting. RESULTS: We
observed endocytosis of GluA1 and 2 exclusively in the anterior cingulate regions
in the remote memory group, one hour post retrieval session, whereas in recent
group, endocytosis of AMPA receptor units was only observed in the hippocampal
regions. The endocytosis of GluA1-2 containing AMPARs upon retrieval, showed the
weakened state of synapse. At this time point modification in content and
strength of memory is possible for treatment of traumatic memories.
PMID- 27614140
TI - Extinction of conditioned cues attenuates incubation of cocaine craving in
adolescent and adult rats.
AB - Relapse to drug use is often precipitated by exposure to drug associated cues
that evoke craving. Cue-induced drug craving has been observed in both animals
and humans to increase over the first few weeks of abstinence and remain high
over extended periods, a phenomenon known as 'incubation of craving'. As
adolescence represents a period of vulnerability to developing drug addiction,
potentially due to persistent reactivity to drug associated cues, we first
compared incubation of cocaine craving in adolescent and adult rats. Adolescent
(P35) and adult (P70) rats were trained to lever press to obtain intravenous
cocaine, with each drug delivery accompanied by a light cue that served as the
conditioned stimulus (CS). Following acquisition of stable responding, rats were
tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence.
Additional groups of rats were also tested after 30days of abstinence, however
these rats were subjected to a cue extinction session 1week into the abstinence
period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like
partial agonist, or vehicle, 30min prior to cue extinction. We found that
adolescent and adult rats acquired and maintained a similar level of cocaine self
administration, and rats of both ages exhibited a higher level of cue-induced
cocaine-seeking if they were tested after 30days of abstinence compared to 1day.
Incubation of cocaine craving was significantly reduced to 1day levels in both
adults and adolescents that received cue extinction training. Administration of
aripiprazole prior to cue extinction did not further reduce cue-induced drug
seeking. These results indicate that cue extinction training during abstinence
may effectively reduce cue-induced relapse at a time when cue-induced drug
craving is usually high.
PMID- 27614142
TI - Differences in navigation performance and postpartal striatal volume associated
with pregnancy in humans.
AB - Pregnancy is accompanied by prolonged exposure to high estrogen levels. Animal
studies have shown that estrogen influences navigation strategies and, hence,
affects navigation performance. High estrogen levels are related to increased use
of hippocampal-based allocentric strategies and decreased use of striatal-based
egocentric strategies. In humans, associations between hormonal shifts and
navigation strategies are less well studied. This study compared 30 peripartal
women (mean age 28years) to an age-matched control group on allocentric versus
egocentric navigation performance (measured in the last month of pregnancy) and
gray matter volume (measured within two months after delivery). None of the women
had a previous pregnancy before study participation. Relative to controls,
pregnant women performed less well in the egocentric condition of the navigation
task, but not the allocentric condition. A whole-brain group comparison revealed
smaller left striatal volume (putamen) in the peripartal women. Across the two
groups, left striatal volume was associated with superior egocentric over
allocentric performance. Limited by the cross-sectional study design, the
findings are a first indication that human pregnancy might be accompanied by
structural brain changes in navigation-related neural systems and concomitant
changes in navigation strategy.
PMID- 27614143
TI - Corrigendum to "Abnormal frontostriatal connectivity in adolescent-onset
schizophrenia and its relationship to cognitive functioning" [Eur. Psychiatry 35C
(2016) 32-38].
PMID- 27614141
TI - Proteolysis, synaptic plasticity and memory.
AB - Protein degradation has many critical functions in the nervous system such as
refinement of synaptic connections during development and synaptic plasticity and
memory in the adult organisms. A major cellular machinery of proteolysis is the
ubiquitin-proteasome pathway (UPP). The UPP precisely regulates proteolysis by
covalently attaching ubiquitin, a small protein, to substrates through sequential
enzymatic reactions and the proteins marked with the ubiquitin tag are degraded
by complex containing many subunits called the proteasome. Research over the
years has shown a role for the UPP in regulating presynaptic and postsynaptic
proteins critical for neurotransmission and synaptic plasticity. Studies have
also revealed a role for the UPP in various forms of memory. Mechanistic
investigations suggest that the function of the UPP in neurons is not homogenous
and is subject to local regulation in different neuronal sub-compartments. In
both invertebrate and vertebrate model systems, local roles have been found for
enzymes that attach ubiquitin to substrate proteins as well as for enzymes that
remove ubiquitin from substrates. The proteasome also has disparate functions in
different parts of the neuron. In addition to the UPP, proteolysis by the
lysosome and autophagy play a role in synaptic plasticity and memory. This review
details the functions of proteolysis in synaptic plasticity and summarizes the
findings on the connection between proteolysis and memory mainly focusing on the
UPP including its local roles.
PMID- 27614144
TI - Early ethanol exposure and vinpocetine treatment alter learning- and memory
related proteins in the rat hippocampus and prefrontal cortex.
AB - This study investigates the effects of early exposure to ethanol on cognitive
function and neural plasticity-related proteins in the rat brain. Sprague-Dawley
rats were administered 12% ethanol solution (4 g/kg/day i.p.) or saline from P4
to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine
whether it could reverse any changes induced by early ethanol exposure. Hence,
from P25 to P31, ethanol-exposed male rats were injected with vinpocetine (20
mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the
open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely
affect spatial memory in the MWM. A key finding in this study was a significant
ethanol-induced change in the function of the phosphorylated extracellular signal
related kinase (P-ERK) signaling pathway in the prefrontal cortex (PFC) and
dorsal hippocampus (DH) of rats that did not display overt behavioral deficits.
The P-ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol
exposed rats compared with controls. Rats that received vinpocetine in addition
to ethanol did not display any behavioral changes but did show alterations in
neural plasticity-related proteins. Mitogen-activated protein kinase phosphatase
was increased, whereas brain-derived neurotrophic factor was decreased, in the
PFC of vinpocetine-treated ethanol-exposed rats, and phosphorylated-glycogen
synthase kinase beta and synaptophysin were increased in the DH of these rats.
This study provides insight into the long-term effects of early ethanol exposure
and its interaction with vinpocetine in the rat brain. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27614145
TI - Midodrine and tolvaptan in patients with cirrhosis and refractory or recurrent
ascites: a randomised pilot study.
AB - BACKGROUND: Splanchnic arterial vasodilatation and subsequent sodium and water
retention play an important role in cirrhotic ascites. Midodrine and tolvaptan
have been used separately in these patients. However, there are no reports on the
use of combination of midodrine and tolvaptan in the control of ascites. The aim
of this study was to evaluate the safety and efficacy of midodrine, tolvaptan and
their combination in control of refractory or recurrent ascites in cirrhotics.
METHODS: Fifty cirrhotic patients with refractory or recurrent ascites were
randomised to receive midodrine (n=13), tolvaptan (n=12) or both (n=13) plus
standard medical therapy (SMT) or SMT alone (n=12). RESULTS: A significant
increase in urinary volume and urinary sodium at 1 and 3 months (P<.05) was
observed in all groups except SMT. There was no worsening of renal or hepatic
function in any group. There was deterioration of model for end-stage liver
disease (MELD) in SMT. Midodrine as well as combination of midodrine and
tolvaptan but not tolvaptan alone was superior to SMT in control of ascites at 3
months (P<.05). The combination therapy was also superior to midodrine in the
control of ascites at 1 month. The morbidity and mortality were similar in all
the groups except SMT. CONCLUSIONS: The results of this pilot study suggest that
midodrine and combination with tolvaptan better controls ascites without any
renal or hepatic dysfunction. The combination therapy rapidly controls ascites as
compared to midodrine or tolvaptan alone.
PMID- 27614147
TI - Binding of human IgG to single-walled carbon nanotubes accelerated
myeloperoxidase-mediated degradation in activated neutrophils.
AB - The binding of protein to carboxylated single-walled carbon nanotubes (SWCNTs)
was believed to play an important role in the biological effects of nanotubes.
However, the effects of protein-SWCNTs interactions on the oxidative degradation
of nanotubes were not stressed enough. Here, we investigated the binding of human
immunoglobulin G (IgG) to SWCNTs, and found that the preferred binding site was
located in the Fc region of IgG. The hydrophobic and electrostatic interactions
might be the crucial factors in stabilizing the binding of SWCNTs with IgG.
Through the competitive binding of IgG and myeloperoxidase (MPO) to nanotube
surfaces, the binding of IgG could impair MPO-induced SWCNTs biodegradation in
vitro. However, both SWCNTs and IgG-SWCNTs were significantly degraded in zymosan
stimulated neutrophils, and the degradation degree was more for IgG-SWCNTs. These
results suggest that the binding of IgG may be an important determinant for MPO
mediated SWCNTs biodegradation in activated human inflammatory cells.
PMID- 27614146
TI - Capillary density: An important parameter in nailfold capillaroscopy.
AB - Nailfold capillaroscopy is one of the various noninvasive bioengineering methods
used to investigate skin microcirculation. It is an effective examination for
assessing microvascular changes in the peripheral circulation; hence it has a
significant role for the diagnosis of Systemic sclerosis with the classic changes
of giant capillaries as well as the decline in capillary density with capillary
dropout. The decline in capillary density is one of microangiopathic features
existing in connective tissue disease. It is detectable with nailfold
capillaroscopy. This parameter is assessed by applying quantitative measurement.
In this article, we reviewed a common method for calculating the capillary
density and the relation between the number of capillaries as well as the
existence of digital ulcers, pulmonary arterial hypertension, autoantibodies,
scleroderma patterns and different scoring system.
PMID- 27614148
TI - Structural insights from a novel invertebrate triosephosphate isomerase from
Litopenaeus vannamei.
AB - Triosephosphate isomerase (TIM; EC 5.3.1.1) is a key enzyme involved in
glycolysis and gluconeogenesis. Glycolysis is one of the most regulated metabolic
pathways, however little is known about the structural mechanisms for its
regulation in non-model organisms, like crustaceans. To understand the structure
and function of this enzyme in invertebrates, we obtained the crystal structure
of triosephosphate isomerase from the marine Pacific whiteleg shrimp (Litopenaeus
vannamei, LvTIM) in complex with its inhibitor 2-phosphogyceric acid (2-PG) at
1.7A resolution. LvTIM assembles as a homodimer with residues 166-176 covering
the active site and residue Glu166 interacting with the inhibitor. We found that
LvTIM is the least stable TIM characterized to date, with the lowest range of
melting temperatures, and with the lowest activation enthalpy associated with the
thermal unfolding process reported. In TIMs dimer stabilization is maintained by
an interaction of loop 3 by a set of hydrophobic contacts between subunits.
Within these contacts, the side chain of a hydrophobic residue of one subunit
fits into a cavity created by a set of hydrophobic residues in the neighboring
subunit, via a "ball and socket" interaction. LvTIM presents a Cys47 at the
"ball" inter-subunit contact indicating that the character of this residue is
responsible for the decrease in dimer stability. Mutational studies show that
this residue plays a role in dimer stability but is not a solely determinant for
dimer formation.
PMID- 27614149
TI - Sirtuins in metabolism, stemness and differentiation.
AB - BACKGROUND: Pluripotent stem cells promise innovative approaches for enduring
diseases, including disease modeling and drug screens. Accordingly, efforts have
been undertaken in order to efficiently reprogram somatic cells to pluripotency,
and then differentiate them into pure cultures of specific cell lineages.
However, the latter step remains mostly elusive, and, in order to better control
differentiation and design more efficient differentiation strategies, the
cellular mechanisms behind different pluripotency stages that mimic embryonic
development are being actively addressed. SCOPE OF REVIEW: Metabolism is one of
many cellular processes that are in constant adjustment during mammalian embryo
development, as well as in pluripotent stem cell establishment and
differentiation. Thus, the role of molecular pathways known to be involved in
metabolic control has been recently addressed as potential modulators of
pluripotency. Notably, mammalian sirtuins have emerged as master regulators of
many cellular processes, including epigenetics and metabolism. In this review we
address the potential developmental role of sirtuins, with a particular focus on
sirtuin 1. MAJOR CONCLUSIONS: This review focuses on the most recent studies
implying sirtuins as regulators of pluripotency and differentiation of
pluripotent stem cells, highlighting metabolic control as associated with the
control of pluripotency. It notably stresses the role of sirtuin 1 in these
processes, creating parallels between in vitro manipulations and developmental
cues. GENERAL SIGNIFICANCE: Using metabolic control in order to determine
cellular fate, both in terms of somatic cell reprogramming to pluripotency and
pluripotent stem cell differentiation, is a topic of increasing interest, and
sirtuins are key players in these efforts.
PMID- 27614150
TI - Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian
Function and Fertility Preservation.
AB - Survivors of pelvic cancer treatment live with the ramifications of pelvic
radiation for many years after their cure. Several options are available to
preserve ovarian function and fertility in reproductive age women undergoing
pelvic radiation. Laparoscopic ovarian transposition is an under-utilized, yet
fairly simple surgical procedure to relocate the ovaries away from the radiation
field. Although randomized-controlled trials on the outcomes of ovarian
transposition are scarce, there is a growing body of evidence on the risks and
benefits of this procedure, in terms of prevention of premature ovarian failure,
and potentially preserving fertility. In this review, we summarize the available
data on the indications, patient selection and outcomes of ovarian transposition,
as well as illustrate the technique of the procedure.
PMID- 27614151
TI - Inpatient Laparoscopic Hysterectomy in the United States: Trends and Factors
Associated With Approach Selection.
AB - STUDY OBJECTIVE: To examine utilization patterns of different laparoscopic
approaches in inpatient hysterectomy and identify patient and hospital
characteristics associated with the selection of specific laparoscopic
approaches. DESIGN: Using data from the 2007 to 2012 National (Nationwide)
Inpatient Sample (NIS), we identified adult women undergoing inpatient
laparoscopic hysterectomy for nonobstetric indications based on International
Classification of Diseases, Ninth Revision, Clinical Modification codes. Benign
cases were categorized based on laparoscopic approach, classified as total
laparoscopic hysterectomy (TLH), laparoscopic-assisted vaginal hysterectomy
(LAVH), or laparoscopic supracervical hysterectomy (LSH). We assessed changes in
the use of these approaches during 2007 to 2012, and used multinomial logistic
regression to examine the association of patient and hospital characteristics
with the choice of laparoscopic approach in 2012. The NIS sample weights were
applied to generate nationally representative estimates. DESIGN CLASSIFICATION:
Retrospective study (Canadian Task Force classification III). SETTING: Hospital
inpatient care nationwide. PATIENTS: Female adult patients in the NIS database
who underwent an inpatient laparoscopic hysterectomy between 2007 and 2012.
INTERVENTION: Inpatient laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS:
Of the inpatient laparoscopic hysterectomies performed in 2012, 83.2% were for
benign indications. The TLH approach accounted for 48.3% of all laparoscopic
hysterectomies, followed by LAVH at 37.3% and LSH at 14.4%. Robotic assistance
was reported in 45.0% of all cases and 72.3% of malignant hysterectomies. An
examination of temporal trends during 2007 to 2012 demonstrates a shift in the
laparoscopic approach from LAVH toward TLH, with a slight decrease in LSH.
Patient race/ethnicity, income, indication for hysterectomy, and comorbid
conditions, as well as hospital teaching status, urban/rural location, bed size,
type of ownership, and geographic region, were significantly associated with the
choice of laparoscopic approach. CONCLUSION: Benign laparoscopic hysterectomy is
increasingly performed as TLH rather than LAVH. In addition to clinical factors,
the selection of laparoscopic approach is influenced by patient socioeconomic and
hospital characteristics.
PMID- 27614152
TI - Impulsivity, implicit attitudes and explicit cognitions, and alcohol dependence
as predictors of pathological gambling.
AB - Impulsivity, implicit attitudes and explicit cognitions regarding gambling, and
alcohol abuse have been pointed out by past research as significant contributors
to the development and maintenance of gambling disorders. In this study, we
tested the relationship among these contributors and pathological gambling. Forty
four pathological gamblers (DSM-5 criteria), of whom 23 were active gamblers and
17 were alcohol dependent, were compared with 100 controls, consisting of
patients with a lifetime history of alcohol use disorder in remission for at
least 2 years. The following protocol was used for the comparison: National
Opinion Research Center Diagnostic Screen for Gambling Disorders, Barratt
Impulsiveness Scale Version 11 (BIS-11), Gambling Related Cognitions Scale
(GRCS), Obsessive Compulsive Drinking Scale, Alcohol Use Disorders Identification
Test, and Gambling Implicit Association Test (IAT). Impulsivity (BIS-11) and
changes in implicit attitudes (IAT) were able to discriminate between
pathological gamblers and controls, the latter being less impulsive and having
fewer implicit attitudes towards gambling. Cognitive impulsivity (BIS-11),
explicit gambling cognitions (GRCS), and alcohol dependence were able to
discriminate between active and non-active pathological gamblers, the latter
having less cognitive impulsivity and less explicit gambling cognitions and
alcohol dependence. Using these simple tools can help clinicians in the
assessment of pathological gambling.
PMID- 27614153
TI - A spreadsheet calculator for estimating biogas production and economic measures
for UK-based farm-fed anaerobic digesters.
AB - This paper presents a spreadsheet calculator to estimate biogas production and
the operational revenue and costs for UK-based farm-fed anaerobic digesters.
There exist sophisticated biogas production models in published literature, but
the application of these in farm-fed anaerobic digesters is often impractical.
This is due to the limited measuring devices, financial constraints, and the
operators being non-experts in anaerobic digestion. The proposed biogas
production model is designed to use the measured process variables typically
available at farm-fed digesters, accounting for the effects of retention time,
temperature and imperfect mixing. The estimation of the operational revenue and
costs allow the owners to assess the most profitable approach to run the process.
This would support the sustained use of the technology. The calculator is first
compared with literature reported data, and then applied to the digester unit on
a UK Farm to demonstrate its use in a practical setting.
PMID- 27614154
TI - Improved production of propionic acid driven by hydrolyzed liquid containing high
concentration of l-lactic acid from co-fermentation of food waste and sludge.
AB - This study investigated the feasibility of improved production propionic acid
enriched volatile fatty acid (VFA) from high concentration (Cs) of food waste and
waste activated sludge (WAS) via lactic acid pathway by using of
Propionibacterium acidipropionici. It was observed that production of l-lactate
overwhelmed to d-lactate at first stage, which improved from 3.21 to 35.45gCOD/L
with increase of substrate Cs. However, kinetic model analysis indicated that P.
acidipropionici growth rate MUmax was decreased with increase of l-lactate
concentration, which explained second stage free cell fermentation of propionic
acid was inhibited when fed by first stage liquid from R-40, R-55 and R-70. Then,
the fibrous bed bioreactor was employed to eliminate the feed inhibition. The
maximal percentage of propionic acid (68.3%) and production (16.31gCOD/L) was
obtained by feeding liquid of R-55, which was improved by 3.33 folds compared to
the free cell fermentation.
PMID- 27614155
TI - Microalgae pretreatment with liquid hot water to enhance enzymatic hydrolysis
efficiency.
AB - Nowadays, microalgae are being considered as promising raw material for
bioethanol production. In this work, three process variables during liquid hot
water (LHW) pretreatment prior to enzymatic hydrolysis by response surface
methodology on Scenedesmus sp. WZKMT were investigated to enhance glucose
recovery. Results indicated that the order of significance for three parameters
was temperature>solid-to-liquid ratio>time. The optimal condition was 1:13 (w/v),
147 degrees C and 40min. The concentration and recovery of glucose under this
condition were 14.223g.L(-1) and 89.32%, respectively, which were up to 5-fold
higher than the samples without LHW pretreatment. In addition, the surface
morphologies of microalgae cells before and after LHW pretreatment were also
verified using scanning electron microscopy (SEM). LHW pretreatment can greatly
enhance the enzymatic efficiency, and can be regarded as an ideal pretreatment
method for glucose recovery from microalgae.
PMID- 27614156
TI - Potential of porous Co3O4 nanorods as cathode catalyst for oxygen reduction
reaction in microbial fuel cells.
AB - This study aims to investigate the potential of porous Co3O4 nanorods as the
cathode catalyst for oxygen reduction reaction (ORR) in aqueous air cathode
microbial fuel cells (MFCs). The porous Co3O4 nanorods were synthesized by a
facile and cost-effective hydrothermal method. Three different concentrations
(0.5mg/cm(2), 1mg/cm(2), and 2mg/cm(2)) of Co3O4 nanorods coated on graphite
electrodes were used to test its performance in MFCs. The results showed that the
addition of porous Co3O4 nanorods enhanced the electrocatalytic activity and ORR
kinetics significantly and the overall resistance of the system was greatly
reduced. Moreover, the MFC with a higher concentration of the catalyst achieved a
maximum power density of 503+/-16mW/m(2), which was approximately five times
higher than the bare graphite electrode. The improved catalytic activity of the
cathodes could be due to the porous properties of Co3O4 nanorods that provided
the higher number of active sites for oxygen.
PMID- 27614157
TI - Enhanced esterification of oleic acid and methanol by deep eutectic solvent
assisted Amberlyst heterogeneous catalyst.
AB - In present study, esterification of oleic acid with methanol using deep eutectic
solvent (DES) assisted Amberlyst heterogeneous catalyst was investigated to
produce biodiesel. Results showed that esterification efficiency was enhanced by
the DES. The combined effect of DES on Amberlyst BD20 (BD20) is better than
Amberlyst 15 (A-15) due to different structure. The optimal reaction conditions
were 12:1M ratio of methanol to oleic acid, 20%(wt/wt) catalyst (BD20-DES (2:8)
and A-15-DES (8:2)) at 85 degrees C for 100min with agitating at 200rpm. The
mechanism involved in catalysis and their capacity to reuse were studied. We
proposed, Choline chloride-glycerol (Chcl-gly) DES could enhance the Amberlyst
function due to the hydrogen bond effect on both DES and water. BD20 has fewer
pores than A-15, have desirable performance in decreasing the inhibition the
water during esterification of high FFA content and provide better performance in
reuse.
PMID- 27614158
TI - An injectable acellular matrix scaffold with absorbable permeable nanoparticles
improves the therapeutic effects of docetaxel on glioblastoma.
AB - Intratumoral drug delivery (IT) is an inherently appealing approach for
concentrating toxic chemotherapies at the site of action. However, for most
chemotherapies, poor tumor penetration and short retention at the administration
site limit their anti-tumor effects. In this work, we describe permeable
nanoparticles (NPs) prepared with a novel amphiphilic polymer, RRR-alpha
tocopheryl succinate-grafted-epsilon-polylysine conjugate (VES-g-epsilon-PLL).
The nanoparticles (NPs) of VES-g-epsilon-PLL exhibited an ultra-small
hydrodynamic diameter (20.8 nm) and positive zeta potential (20.6 mV), which
facilitate strong glioma spheroid penetration ability in vitro. Additionally, the
hydrophobic model drug docetaxel (DTX) could be effectively encapsulated in the
nanoparticles with 3.99% drug loading and 73.37% encapsulation efficiency. To
prolong the retention time of DTX-loaded nanoparticles (DTX-NPs) in the tumor,
intact decellularized brain extracellular matrix (dBECM) derived from healthy
rats was used as a drug depot to adsorb the ultra-small DTX-NPs. The intact DTX
NPs-adsorbing dBECM scaffold was further homogenized into an injectable DTX-NPs
dBECM suspension for intratumoral administration. The DTX-NPs-dBECM suspension
exhibited slower DTX release than naked DTX-NPs without compromising the tumor
penetration ability of DTX-NPs. An antitumor study showed that the DTX-NPs-dBECM
suspension exhibited more powerful in vitro inhibition of tumor spheroid growth
than free DTX solution or DTX-NPs. Due to strong tumor penetration ability and
prolonged retention, DTX-NPs-dBECM led to complete suppression of glioma growth
in vivo at 28 days after treatment. The therapeutic mechanism was due to enhanced
proliferation inhibition and apoptosis of tumor cells and angiogenesis inhibition
of glioma after treatment with DTX-NPs-dBECM. Finally, the safety of DTX-NPs
dBECM at the therapeutic dose was demonstrated via pathological HE assay from
heart, liver, spleen, lung and kidney tissues. In conclusion, permeable
nanoparticle-absorbing dBECM is a potential carrier for intratumoral delivery of
common chemotherapeutics.
PMID- 27614159
TI - Pro-fibrotic effects of PFKFB4-mediated glycolytic reprogramming in fibrous
dysplasia.
AB - Fibrous dysplasia (FD) caused by a mosaic somatic mutation of GNAS is
characterized by replacement of the affected bone with abnormal fibrous tissue.
Herein, we present novel disease models for FD developed with pairs of isogenic
wild-type and GNAS(R201H)-mutated induced pluripotent stem cells (iPSCs) and
their derivative mesenchymal stem cells (MSCs). Both 2D and 3D MSC culture models
for FD successfully reflect FD's typical molecular characteristics, such as
enhanced cAMP level, PKA activity, CREB1 phosphorylation and the pathologic
fibrotic phenotype. The fibrotic features of GNAS(R201H) FD model cells were
closely linked to augmented glycolysis and depended on glycolytic PFKFB4 and the
activation of pro-fibrotic TGFbeta signalling. Either depletion of PFKFB4 or
inhibition of glycolysis or TGFbeta signalling potentially blocked fibrosis
progression in GNAS(R201H) FD model cells. Our FD models could facilitate a
better mechanistic understanding of FD and help develop effective therapeutics
for FD and other fibrosis diseases.
PMID- 27614160
TI - Human tissue engineering allows the identification of active miRNA regulators of
glioblastoma aggressiveness.
AB - Glioblastoma multiforme (GBM) is among the most aggressive cancers associated
with massive infiltration of peritumoral parenchyma by migrating tumor cells. The
infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with
redundant signaling pathways likely underlie the inability of conventional and
targeted therapies to achieve long-term remissions. In this respect, microRNAs
(miRNAs), which are endogenous small non-coding RNAs that play a role in cancer
aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic
targets for treatment of malignant gliomas. We previously described a tissue
model of GBM developing into a stem cell-derived human Engineered Neural Tissue
(ENT) that allows the study of tumor/host tissue interaction. Combined with high
throughput sequencing analysis, we took advantage of this human and integrated
tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and
1293) active on cell proliferation, adhesion to extracellular matrix and tumor
cell invasion were identified in GBM cells developing within ENT, and also
confirmed in GBM biopsies. The components of miRNAs regulatory network at the
transcriptional and the protein level have been also revealed by whole
transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR
340 has a clinical relevance and modulates the expression of miR-494 and -1293,
emphasizing its biological significance. Altogether, these findings demonstrate
that human tissue engineering modeling GBM development in neural host tissue is a
suitable tool to identify active miRNAs. Collectively, our study identified miR
340 as a strong modulator of GBM aggressiveness which may constitute a
therapeutic target for treatment of malignant gliomas.
PMID- 27614161
TI - Magnetically guided delivery of DHA and Fe ions for enhanced cancer therapy based
on pH-responsive degradation of DHA-loaded Fe3O4@C@MIL-100(Fe) nanoparticles.
AB - Dihydroartemisinin (DHA) has been investigated in cancer therapy for its reactive
oxygen species (ROS) based cytotoxicity originated from interacting with ferrous
ions that may reduce or eliminate the multidrug resistance commonly associated
with conventional chemotherapy agents. However, synchronously delivery of
hydrophobic DHA and Fe (III) ions into tumor cells remains a major challenge. In
this work, we develop novel Fe3O4@C@MIL-100(Fe) (FCM) nanoparticles for
synchronously delivery of DHA and Fe (III) for cancer therapy. The MOFs structure
based on Fe (III) carboxylate materials MIL-100 (Fe) holds great potential for
storage/delivery of hydrophobic drug DHA. As a unique nanoplatform, the hybrid
inorganic-organic drug delivery vehicles show pH-responsive biodegradation and
synchronous releasing of DHA and Fe (III) upon reaching tumor sites. The
intracellular Fe (III) will be reduced further to ferrous ion and interact with
DHA to increase its cytotoxicity. The potential of this alternative anti-tumor
modality is demonstrated in vivo due to an increased intracellular accumulation
of DHA in tumor and activated mechanism via co-release of DHA and Fe (III),
especially under the guidance of an external applied magnetic field.
PMID- 27614162
TI - Nanostructured recombinant cytokines: A highly stable alternative to short-lived
prophylactics.
AB - Cytokines have been widely used as adjuvants and therapeutic agents in treatments
of human diseases. Despite their recognized potential as drugs, the medical use
of cytokines has considerable drawbacks, mainly related to their low stability
and short half-life. Such intrinsic limitations imply the administration of high
doses, often prompting toxicity, undesirable side effects and greater production
costs. Here, we describe a new category of mechanically stable nanostructured
cytokines (TNFalpha and CCL4/MIP-1beta) that resist harsh physicochemical
conditions in vitro (pH and temperature), while maintaining functionality. These
bio-functional materials are produced in recombinant cell factories through cost
effective and fully scalable processes. Notably, we demonstrate their
prophylactic potential in vivo showing they protect zebrafish from a lethal
infection by Pseudomonas aeruginosa.
PMID- 27614163
TI - Grafting PNIPAAm from beta-barrel shaped transmembrane nanopores.
AB - The research on protein-polymer conjugates by grafting from the surface of
proteins has gained significant interest in the last decade. While there are many
studies with globular proteins, membrane proteins have remained untouched to the
best of our knowledge. In this study, we established the conjugate formation with
a class of transmembrane proteins and grow polymer chains from the ferric
hydroxamate uptake protein component A (FhuA; a beta-barrel transmembrane protein
of Escherichia coli). As the lysine residues of naturally occurring FhuA are
distributed over the whole protein, FhuA was reengineered to have up to 11
lysines, distributed symmetrically in a rim on the membrane exposed side
(outside) of the protein channel and exclusively above the hydrophobic region.
Reengineering of FhuA ensures a polymer growth only on the outside of the beta
barrel and prevents blockage of the channel as a result of the polymerization. A
water-soluble initiator for controlled radical polymerization (CRP) was
consecutively linked to the lysine residues of FhuA and N-isopropylacrylamide
(NIPAAm) polymerized under copper-mediated CRP conditions. The conjugate
formation was analyzed by using MALDI-ToF mass spectrometry, SDS-PAGE, circular
dichroism spectroscopy, analytical ultracentrifugation, dynamic light scattering,
transmission electron microscopy and size exclusion chromatography. Such
conjugates combine the specific functions of the transmembrane proteins, like
maintaining membrane potential gradients or translocation of substrates with the
unique properties of synthetic polymers such as temperature and pH stimuli
handles. FhuA-PNIPAAm conjugates will serve as functional nanosized building
blocks for applications in targeted drug delivery, self-assembly systems,
functional membranes and transmembrane protein gated nanoreactors.
PMID- 27614165
TI - Checkpoint inhibitors in chronic kidney failure and an organ transplant
recipient.
AB - BACKGROUND: Immune-checkpoint inhibitors have been approved for the treatment of
metastatic melanoma based on several phase III trials. Patients after organ
transplantation and patients with impaired renal function were excluded from
these studies. Recently, allograft rejections were reported in organ transplant
recipients receiving PD-1 blocking antibodies. PATIENTS AND FINDINGS: Four
patients with metastatic melanoma and impaired kidney function (baseline serum
creatinine 1.79-2.59 mg/dl) were treated with immune-checkpoint blockers, of
which one was a kidney-transplant recipient receiving immunosuppressive therapy
with tacrolimus and prednisolone. The patient was initially treated with the anti
CTLA-4 antibody ipilimumab after detailed explanation of the potential risk of
allograft rejection. Upon disease progression, therapy was switched to the anti
PD-1 antibody nivolumab. The other three patients were treated with nivolumab or
pembrolizumab, two of them after previous therapy with ipilimumab. RESULTS: The
patients received a median of six doses (range 3-21) of anti-PD-1 antibodies and
3-4 doses of ipilimumab. Kidney function tests remained stable throughout the
course of checkpoint blockade. In the kidney transplant recipient, neither
ipilimumab nor nivolumab led to an allograft rejection. Responses to anti-PD-1
treatment were divergent with two patients showing disease progression, one
achieving a mixed response and one experiencing a complete response. CONCLUSION:
These cases show that checkpoint inhibitors can be a safe therapeutic option in
patients with impaired kidney function. Furthermore, we report the first organ
transplant patient with malignant melanoma who received ipilimumab followed by
nivolumab without experiencing a kidney allograft rejection.
PMID- 27614164
TI - No breast cancer subgroup can be spared postoperative radiotherapy after breast
conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group
randomised trial, SweBCG 91 RT.
AB - BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an
established treatment for women with T1-2N0 breast cancers. Since subgroups of
patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is
important to study whether RT is necessary for all patients. PATIENTS AND
METHODS: A total of 1187 women with primary T1-2N0M0 breast cancer were
randomised, after standardised sector resection, to postoperative whole breast RT
or no local treatment. Adjuvant systemic therapy was offered to patients with
stage II cancers. Patients were followed with clinical examinations and annual
mammography for 10 years and thereafter referred to the Swedish mammography
screening program. RESULTS: After 15 years of follow-up, a higher cumulative
incidence of IBTR was observed in control patients, 23.9%, versus irradiated
patients, 11.5%, P<0.001. Recurrence-free survival was inferior, 51.7% versus
60.4%, P=0.0013. The main effect of RT was seen during the first 5 years.
However, overall survival was not significantly lower 68.4% versus 71.1%, P=0.68,
nor was breast cancer-specific mortality significantly higher. CONCLUSIONS: RT
after BCS significantly reduced the incidence of IBTR at 15 years of follow-up.
We were unable to identify subgroups which could be spared RT. Breast cancer
mortality was not significantly reduced after RT. Good predictive markers for
radiation sensitivity and improved adjuvant systemic therapy are needed to omit
RT after BCS.
PMID- 27614166
TI - The impact of splenectomy on human coronary artery atherosclerosis and vascular
macrophage distribution.
AB - BACKGROUND: Splenectomy can potentially impact atherosclerosis through multiple
mechanisms including altered lipid homeostasis, increased coagulation, and
altered macrophage recruitment to the plaque. In patients, splenectomy has been
associated with increased rates of coronary artery events, while in experimental
mice, splenectomy causes increased atherosclerosis but reduces systemic monocyte
supply. In this study, the direct impact of splenectomy on human coronary artery
atherosclerotic plaque severity and macrophage content was investigated. METHODS:
Coronary artery atherosclerotic plaque severity was determined at autopsy in 18
long-term (>=10 years) splenectomy patients and 90 matched control patients.
Coronary artery macrophage content was evaluated in mild atherosclerotic plaques
of 11 mid- to long-term (>=1 year) splenectomy patients and 11 matched control
patients. RESULTS: Splenectomy was associated with reduced coronary artery
atherosclerosis (P=.03). The association was most pronounced for the subgroup of
patients who had undergone splenectomy 20 years or more prior to death (P=.02).
There was no difference in the density of macrophages in the plaque, media, or
adventitia upon comparing splenectomy and control patients. In the control group,
there was no correlation between the macrophage densities in the three arterial
layers. However, in the splenectomy patients, there was a strong correlation in
the macrophage densities across the plaque, media, and adventitia (P<=.0002),
with resulting slopes that were significantly greater than seen in the control
patients (P=.0007-.011). CONCLUSIONS: These findings indicate that, in humans,
splenectomy is associated with lower coronary artery atherosclerotic plaque
severity and altered coronary artery macrophage distribution. These results
suggest that the spleen can modulate the recruitment of macrophages into human
coronary arteries and the progression of atherosclerosis.
PMID- 27614167
TI - A retrospective study of postmortem heart weight in an adult Norwegian
population.
AB - The aim of the study is to get a better understanding of what a normal heart
weight is and to provide updated reference tables applicable in a Caucasian
population. Most previous studies are outdated and often based on other ethnic
populations, and these studies are often used in reference tables in pathology
textbooks. We included 692 Caucasian subjects, age 20-98years, out of 2834
autopsies performed at the Department of Pathology and Genetics, St. Olavs
Hospital-University Hospital of Trondheim between 2003 and 2012. Subjects with
various heart or other chronic diseases were excluded. Regression analysis was
applied to evaluate the relationship between heart weight and age, gender, body
weight, height, body mass index and body surface area. We provide updated
reference tables and discuss different approaches to the estimation of heart
weight.
PMID- 27614168
TI - Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary
artery ligation in rats.
AB - BACKGROUND: Two potent carbonic anhydrase (CA) inhibitors with widely differing
membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible
ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac
dysfunction in rats subjected to coronary artery ligation (CAL)-induced
myocardial infarction. METHODS AND RESULTS: Rats with evidence of heart failure
(HF) at 32 weeks following a permanent left anterior coronary artery occlusion
were treated with placebo, BZ, or ETZ (4 mg kgday-1) for 4 weeks at which time
left ventricular function and structure were evaluated. Lung weight/body weight
(LW/BW) ratio increased in CAL rats by 17+/-1% vs. control, suggesting pulmonary
edema. There was a trend for BZ and ETZ to ameliorate the increase in LW/BW by
almost 50% (9+/-5% and 9+/-8%, respectively, versus CAL) (P=.16, NS).
Echocardiographic assessment showed decreased left ventricular midwall shortening
in HF rats, 21+/-1% vs. control 32+/-1%, which was improved by BZ to 29+/-1% and
ETZ to 27+/-1%, and reduced endocardial shortening in HF rats 38+/-3% vs. control
62+/-1%, partially restored by BZ and ETZ to ~50%. Expression of the hypoxia
inducible membrane-associated CAIX isoform increased by ~60% in HF rat hearts,
and this effect was blocked by ETZ. CONCLUSIONS: We conclude that CAL-induced
myocardial interstitial fibrosis and associated decline in left ventricular
function were diminished with BZ or ETZ treatment. The reductions in cardiac
remodeling in HF with both ETZ and BZ CA inhibitors suggest that inhibition of a
membrane-bound CA appears to be the critical site for this protection.
PMID- 27614170
TI - Ear health and hearing surveillance in girls and women with Turner's syndrome:
recommendations from the Turner's Syndrome Support Society.
AB - BACKGROUND: Turner's syndrome (TS) is a common chromosomal disorder, affecting
one in 2000 newborn girls, in which part or all of one X chromosome is missing.
Ear and hearing problems are very common in girls and women with TS. The aim of
this review was to review the published literature to suggest recommendations for
otological health surveillance. METHOD: A keyword search of Ovid Medline was
performed for published literature on the subject and evidence rated according to
the GRADE criteria. RESULTS: Middle ear disorders are very common and persistent
in girls and women with TS as are progressive sensorineural hearing loss and
balance disorders. CONCLUSIONS: Otolaryngologists should be aware of the high
prevalence and challenging nature of all forms of ear disease in individuals with
TS. Early intervention may offer benefits to health and education, and we
advocate routine lifelong annual hearing screening in this group.
PMID- 27614169
TI - Endoglin selectively modulates transient receptor potential channel expression in
left and right heart failure.
AB - INTRODUCTION: Transient receptor potential (TRP) channels are broadly expressed
cation channels that mediate diverse physiological stimuli and include canonical
(TRPC), melastatin (TRPM), and vanilloid (TRPV) subtypes. Recent studies have
implicated a role for TRPC6 channels as an important component of signaling via
the cytokine, transforming growth factor beta 1 (TGFbeta1) in right (RV) or left
ventricular (LV) failure. Endoglin (Eng) is a transmembrane glycoprotein that
promotes TRPC6 expression and TGFbeta1 activity. No studies have defined
biventricular expression of all TRP channel family members in heart failure.
HYPOTHESIS: We hypothesized that heart failure is associated with distinct
patterns of TRP channel expression in the LV and RV. METHODS: Paired viable LV
and RV free wall tissue was obtained from human subjects with end-stage heart
failure (n=12) referred for cardiac transplantation or biventricular assist
device implantation. Paired LV and RV samples from human subjects without heart
failure served as controls (n=3). To explore a functional role for Eng as a
regulator of TRP expression in response to RV or LV pressure overload, wild-type
(Eng+/+) and Eng haploinsufficient (Eng+/-) mice were exposed to thoracic aortic
(TAC) or pulmonary arterial (PAC) constriction for 8weeks. Biventricular tissue
was analyzed by real-time polymerase chain reaction. RESULTS: Compared to
nonfailing human LV and RV samples, mRNA levels of TRPC1, 3, 4, 6, and TRPV-2
were increased and TRPM2, 3, and 8 were decreased in failing LV and RV samples.
TRPC1 and 6 levels were higher in failing RV compared to failing LV samples.
After TAC, murine LV levels of TPRC1 and 6 were increased in both Eng+/+ and
Eng+/- mice compared to sham controls. LV levels of TRPC4, TRPM3 and 7, TRPV2 and
4 were increased in Eng+/+, not in Eng+/- mice after TAC. After PAC, all TRP
channel family members were increased in the RV, but not LV, of Eng+/+ compared
to sham controls. In contrast to Eng+/+, PAC did not increase RV or LV levels of
TRP channels in Eng+/- mice. CONCLUSIONS: This is the first study to demonstrate
that TRP channels exhibit distinct profiles of expression in the LV and RV of
patients with heart failure and in murine models of univentricular pressure
overload. We further introduce that the TGFbeta1 coreceptor Eng selectively
regulates expression of multiple TRP channels in the setting of LV or RV pressure
overload.
PMID- 27614171
TI - Epithelial ovarian cancer and type of peritoneal insult: a case-control study.
AB - OBJECTIVE: To evaluate the association between different types of peritoneal
insults and the development of sporadic epithelial ovarian cancer (EOC) subtypes
in the general population. STUDY DESIGN: Hospital based case control study
comparing sporadic cases of EOC with age matched control group between 2003 and
2008. Medical, surgical, and gynecological histories were compared between 208
women with histological diagnosis of EOC and 224 women in the control group
matched for age at presentation for well woman examination. RESULTS: 18% patients
in the study population and 5% patients in the control group had history of
diverticulosis (OR 7.3, 95% CI 2.8-19.1). 10% patients in the study populations
and 39% patients in the control group had history of diabetes mellitus (OR 0.41,
95% CI 0.23-0.75). Sub classification of EOC into type 1 and type 2 further
revealed 12% patients (OR 0.44, 95% CI 0.22-0.87) in type 1 group, 35% patients
(OR 0.43, 95% CI 0.27-0.69) in type 2 group, and 71% patients in the control
group had no prior surgical history. Furthermore, 3% patients (OR 0.27; 95% CI
0.08-0.9) in the type 1 group, 48% patients (OR 2.0, CI 95% 1.24-3.24) in the
type 2 group, and 41% patients in the control group had history of bilateral
tubal ligation (BTL). CONCLUSION: A significant association was found between
diverticulosis, hysterectomy and endometriosis increasing the likelihood of type
1 EOC; while diverticulosis, exploratory laparotomy and hysterectomy increased
the likelihood of type 2 EOC. BTL was significantly associated with decreasing
the likelihood of type 1 EOC, but increasing the likelihood of type 2 EOC.
Diabetes mellitus and no prior surgical history were found to significantly
decrease the likelihood of all EOC.
PMID- 27614172
TI - Current Perspectives on Left Ventricular Geometry in Systemic Hypertension.
AB - Hypertension (HTN) is a global health problem and a leading risk factor for
cardiovascular disease (CVD) morbidity and mortality. The hemodynamic overload
from HTN causes left ventricular (LV) remodeling, which usually manifests as
distinct alterations in LV geometry, such as concentric remodeling or concentric
and eccentric LV hypertrophy (LVH). In addition to being a common target organ
response to HTN, LV geometric abnormalities are well-known independent risk
factors for CVD. Because of their prognostic implications and quantifiable
nature, changes in LV geometric parameters have commonly been included as an
outcome in anti-HTN drug trials. The purpose of this paper is to review the
relationship between HTN and LV geometric changes with a focus on (1) diagnostic
approach, (2) epidemiology, (3) pathophysiology, (4) prognostic effect and (5) LV
response to anti-HTN therapy and its impact on CVD risk reduction.
PMID- 27614173
TI - Cyanobacterial metabolic engineering for biofuel and chemical production.
AB - Rising levels of atmospheric CO2 are contributing to the global greenhouse
effect. Large scale use of atmospheric CO2 may be a sustainable and renewable
means of chemical and liquid fuel production to mitigate global climate change.
Photosynthetic organisms are an ideal platform for efficient, natural CO2
conversion to a broad range of chemicals. Cyanobacteria are especially attractive
for these purposes, due to their genetic malleability and relatively fast growth
rate. Recent years have yielded a range of work in the metabolic engineering of
cyanobacteria and have led to greater knowledge of the host metabolism.
Understanding of endogenous and heterologous carbon regulation mechanisms leads
to the expansion of productive capacity and chemical variety. This review
discusses the recent progress in metabolic engineering of cyanobacteria for
biofuel and bulk chemical production since 2014.
PMID- 27614174
TI - Enzymatic deconstruction of plant biomass by fungal enzymes.
AB - Lignocellulosic plant biomass is the world's most abundant carbon source and has
consequently attracted attention as a renewable resource for production of
biofuels and commodity chemicals. Still the process is economically not fit
enough to compete with then use of fossil resources, and the costs associated
with enzymatic hydrolysis and product recovery are the major obstacle. The
discovery of the role of non-hydrolytic enzymes in lignocellulose hydrolysis has
recently contributed significant improvements to hydrolysis but also added new
challenges to the biomass to ethanol process. Transfer of the new insights to the
industrial scale and shaping the enzymes to tolerate associated adverse
conditions has now shown first success, thus optimizing the economy of cellulosic
ethanol (or other biofuel) production.
PMID- 27614175
TI - The effects of juvenile hormone on Lasius niger reproduction.
AB - Reproduction has been shown to be costly for survival in a wide diversity of
taxa. The resulting trade-off, termed the reproduction-survival trade-off, is
thought to be one of the most fundamental forces of life-history evolution. In
insects the pleiotropic effect of juvenile hormone (JH), antagonistically
regulating reproduction and pathogen resistance, is suggested to underlie this
phenomenon. In contrast to the majority of insects, reproductive individuals in
many eusocial insects defy this trade-off and live both long and prosper. By
remodelling the gonadotropic effects of JH in reproductive regulation, the queens
of the long-lived black garden ant Lasius niger (living up to 27 years), have
circumvented the reproduction-survival trade off enabling them to maximize both
reproduction and pathogen resistance simultaneously. In this study we measure
fertility, vitellogenin gene expression and protein levels after experimental
manipulation of hormone levels. We use these measurements to investigate the
mechanistic basis of endocrinological role remodelling in reproduction and
determine how JH suppresses reproduction in this species, rather then stimulating
it, like in the majority of insects. We find that JH likely inhibits three key
aspects of reproduction both during vitellogenesis and oogenesis, including two
previously unknown mechanisms. In addition, we document that juvenile hormone, as
in the majority of insects, has retained some stimulatory function in regulating
vitellogenin expression. We discuss the evolutionary consequences of this complex
regulatory architecture of reproduction in L. niger, which might enable the
evolution of similar reproductive phenotypes by alternate regulatory pathways,
and the surprising flexibility regulatory role of juvenile hormone in this
process.
PMID- 27614177
TI - Inter-individual variation in nutrient balancing in the honeybee (Apis
mellifera).
AB - The Geometric Framework approach in nutritional ecology postulates that animals
attempt to balance the consumption of different nutrients rather than simply
maximizing energetic gain. The intake target with respect to each nutrient
maximizes fitness in a specific dimension and any difference between individuals
in intake target therefore represents alternative behavioral and fitness
maximization strategies. Nutritional interactions are a central component of all
social groups and any inter-individual variation in intake target should
therefore have a significant influence on social dynamics. Using the honeybee
colony as an experimental model, we quantified differences in the carbohydrate
intake target of individual foragers using a capillary feeder (CAFE) assay. Our
results show that the bees did not simply maximize their net energetic gain, but
combined sugar and water in their diet in a way that brought them to an intake
target equivalent to a 33% sucrose solution. Although the mean intake target with
respect to the nutrients sucrose and water was the same under different food
choice regimens, there was significant inter-individual variation in intake
target and the manner in which individuals reached this target, a variation which
suggests different levels of tolerance to nutrient imbalance. We discuss our
results in the context of how colony performance may be influenced by the
different nutrient balancing strategies of individual members and how such
nutritional constraints could have contributed to the evolution of sociality.
PMID- 27614176
TI - Measuring activity in olfactory receptor neurons in Drosophila: Focus on spike
amplitude.
AB - Olfactory responses at the receptor level have been thoroughly described in
Drosophila melanogaster by electrophysiological methods. Single sensilla
recordings (SSRs) measure neuronal activity in intact individuals in response to
odors. For sensilla that contain more than one olfactory receptor neuron (ORN),
their different spontaneous spike amplitudes can distinguish each signal under
resting conditions. However, activity is mainly described by spike frequency.
Some reports on ORN response dynamics studied two components in the olfactory
responses of ORNs: a fast component that is reflected by the spike frequency and
a slow component that is observed in the LFP (local field potential, the single
sensillum counterpart of the electroantennogram, EAG). However, no apparent
correlation was found between the two elements. In this report, we show that
odorant stimulation produces two different effects in the fast component,
affecting spike frequency and spike amplitude. Spike amplitude clearly diminishes
at the beginning of a response, but it recovers more slowly than spike frequency
after stimulus cessation, suggesting that ORNs return to resting conditions long
after they recover a normal spontaneous spike frequency. Moreover, spike
amplitude recovery follows the same kinetics as the slow voltage component
measured by the LFP, suggesting that both measures are connected. These results
were obtained in ab2 and ab3 sensilla in response to two odors at different
concentrations. Both spike amplitude and LFP kinetics depend on odorant,
concentration and neuron, suggesting that like the EAG they may reflect olfactory
information.
PMID- 27614178
TI - A review of computed tomography and manual dissection for calibration of devices
for pig carcass classification - Evaluation of uncertainty.
AB - Online pig carcass classification methods require calibration against a reference
standard. More than 30years ago, the first reference standard in the EU was
defined as the total amount of lean meat in the carcass obtained by manual
dissection. Later, the definition was simplified to include only the most
important parts of the carcass to obtain a better balance between accuracy and
cost. Recently, computed tomography (CT) obtained using medical X-ray scanners
has been proposed as a reference standard. The error sources of both traditional
(manual) dissection methods and the new methods based on images from CT scanning
of pig carcasses are discussed in this paper. The uncertainty resulting from the
effect of various error sources is estimated. We conclude that, without
standardisation, the uncertainty is considerable for all the methods. However,
methods based on volume estimation using CT and image analysis might lead to
higher accuracy if necessary precautions are taken with respect to measuring
protocol and reference materials.
PMID- 27614179
TI - Effect of immunocastration with Bopriva on carcass characteristics and meat
quality of feedlot Holstein bulls.
AB - To evaluate the effect of immunocastration on carcass and meat characteristics,
Holstein bulls aged between 7 and 8months with a live weight of 232+/-1.19kg were
given two separate treatments, placebo (intact bulls) versus Bopriva, and then
slaughtered after approximately 239days of fattening. While the testosterone
levels in intact bulls remained at 0.42ng/ml throughout the study, by day 181,
differences (P<0.05) were observed in immunized bulls, with values of 0.21ng/ml.
The carcasses of animals treated with Bopriva recorded both a higher hot carcass
weight (HCW) and a cold carcass weight (CCW), as well as higher dorsal fat
density, marbling and KPH (P<0.05); however, no differences (P>0.05) were
observed in the Longissimus lumborum area. No significant differences (P>0.05)
were recorded between the treatments for pH, L*, a*, b* C* and H*. The carcasses
of the animals treated with Bopriva were heavier, with higher dorsal fat density
and marbling score.
PMID- 27614180
TI - Impact of lysine and liquid smoke as flavor enhancers on the quality of low-fat
Bologna-type sausages with 50% replacement of NaCl by KCl.
AB - Low-fat Bologna-type sausages were produced with 50% of NaCl replaced by KCl and
with addition of lysine and/or liquid smoke as flavor enhancers. The influence of
sodium reduction on technological, physicochemical, and microbiological
properties was determined. In addition, the sensory properties were evaluated
using a Check all that apply questionnaire (CATA) and a consumer study. The
partial replacement of NaCl by KCl did not have negative impacts on
physicochemical, technological, and microbiological properties. However, the
addition of KCl affected the sensory acceptance, as consumers identified by CATA
questionnaire a reduction in salty taste and an increase in bitter, astringent,
and metallic taste. The isolated or combined addition of lysine and liquid smoke
reduced the sensory quality defects caused by the addition of KCl. Therefore,
high quality low-fat Bologna-type sausages with sodium reduction close to 50% can
be produced by replacing 50% NaCl by KCl and with addition of 1% lysine and/or
0.1% liquid smoke.
PMID- 27614181
TI - Involvement of the TRPV1 receptor in plasma extravasation in airways of rats
treated with an angiotensin-converting enzyme inhibitor.
AB - Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment
of hypertension, congestive heart failure and renal disease, and are considered
relatively safe and generally well-tolerated drugs. However, adverse effects of
ACEIs have been reported, including non-productive cough and angioedema, which
can lead to poor adherence to therapy. The mechanisms by which ACEIs promote
adverse effects are not fully elucidated, although increased bradykinin plasma
levels following ACEI therapy seem to play an important role. Since bradykinin
can sensitise the transient potential vanilloid receptor 1 (TRPV1), we
investigated the role of TRPV1 in plasma extravasation in the trachea and bronchi
of rats treated with the ACEI captopril. We observed that intravenous (i.v.)
administration of captopril did not cause plasma extravasation in the trachea or
bronchi of spontaneously breathing rats, but induced plasma extravasation in the
trachea and bronchi of artificially ventilated rats. The intratracheal (i.t.)
instillation of capsaicin or bradykinin also induced an increase in plasma
extravasation in the trachea and bronchi of artificially ventilated rats. As
expected, capsaicin-induced plasma extravasation was inhibited by i.t.
pretreatment with the TRPV1 selective antagonist capsazepine (CPZ) while
bradykinin-induced plasma extravasation was reduced by i.t. pretreatment with the
selective B2 receptor antagonist Icatibant, originally known as HOE 140 (HOE).
Interestingly, bradykinin-induced plasma extravasation was also inhibited by CPZ.
The pretreatment with HOE and CPZ, singly or in combination and at doses which do
not cause inhibitory effects per se, significantly inhibited the plasma
extravasation induced by captopril treatment in artificially ventilated rats. In
addition, treatment with a high dose of capsaicin in newborn rats, which induces
degeneration of TRPV1-expressing sensory neurons, abolished both capsaicin and
captopril-induced plasma extravasation in artificially ventilated rats. In
conclusion, our study identified that captopril treatment promoted sensitisation
of TRPV1, via B2 receptor activation, inducing plasma extravasation in the
airways of mechanically ventilated rats. The present findings add a new view
about the role of TRPV1 in the plasma extravasation induced by captopril and
could to contribute to the elucidation of mechanisms by which ACEI induces
adverse effects on airways.
PMID- 27614182
TI - Sedimentary records of recent sea level rise and acceleration in the Yucatan
Peninsula.
PMID- 27614183
TI - Biodegradation of phenanthrene by Rhizobium petrolearium SL-1.
AB - AIMS: We aimed to investigate the phenanthrene degradation characteristics and
possible phenanthrene degradation pathways of Rhizobium petrolearium SL-1.
METHODS AND RESULTS: Using high-performance liquid chromatography (HPLC), UV
visible and gas chromatography-mass spectrometry (GC-MS) analysis, the
phenanthrene-degrading properties and metabolites of Rh. petrolearium SL-1 were
analysed, and then combined with genome-based analysis to elucidate the possible
biodegradation pathway of phenanthrene in Rh. petrolearium SL-1. The results of
the analyses showed that phenanthrene (100 mg l-1 ) was completely degraded by
strain SL-1 at 35 degrees C, 0.02% salinity and pH 9.0 within 3 days. A wide
range of polycyclic aromatic hydrocarbons, including naphthalene, fluorene,
anthracene and pyrene, could also be degraded by this strain. CONCLUSIONS: Based
on the identified metabolites, the utilization of probable intermediates and the
presence of putative phenanthrene catabolic genes, we concluded that phenanthrene
was degraded via two different routes, namely the 'naphthalene' and the 'phthalic
acid' routes. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, this
study shows the degradation pathway of phenanthrene by a Rhizobium strain.
Because of its excellent stress resistance, metabolic versatility, high
degradation efficiency and potential application in phytoremediation, Rh.
petrolearium SL-1 is a potential candidate for the bioremediation of polycyclic
aromatic hydrocarbons-contaminated areas.
PMID- 27614184
TI - Vibrational sensitivity of the subgenual organ complex in female Sipyloidea
sipylus stick insects in different experimental paradigms of stimulus direction,
leg attachment, and ablation of a connective tibial sense organ.
AB - We document the sensitivity to sinusoidal vibrations for chordotonal organs in
the stick insect tibia (Sipyloidea sipylus). In the tibia, the scolopidial
subgenual organ (~40 scolopidial sensilla), distal organ (~20 scolopidial
sensilla), and distal tibial chordotonal organ (~7 scolopidial sensilla) are
present. We study the sensitivity of tibial sensory organs in all leg pairs to
vibration stimuli as sensory thresholds by recording summed action potentials
from Nervus cruris in the femur. The tibia was stimulated with a minishaker
delivering vibrational stimuli. Because different experimental procedures may
affect the vibration sensitivity, we here analysed possible effects of different
experimental conditions: (1) the stimulus direction delivered in either
horizontal or vertical direction to the leg; (2) recording responses only from
the subgenual organ complex after ablation of the distal tibial chordotonal
organ, and (3) the attachment of the leg to the minishaker by plastilin, beeswax
colophony, or freely standing legs. The tibial scolopidial organs give summed
responses to vibration stimuli with highest sensitivity between 500 and 1000Hz
for all leg pairs. In the different experimental series, we find that (1)
thresholds were influenced by stimulation direction with lower thresholds in
response to vertical vibrations, (2) ablating the distal tibial chordotonal organ
by cutting the distal-most tibia did not change the summed sensory thresholds
significantly, and (3) the attachment material between legs and the minishaker
(plastilin or beeswax-colophony mixture) did not significant influence the
sensory thresholds against free-standing tarsi. The distal tibial chordotonal
organ is a connective chordotonal organ attached to a tendon and is likely a
proprioceptive organ. These results emphasise that vibrational thresholds are
mainly direction-sensitive. Thus, the direction of stimulus delivery during
electrophysiological recordings is relevant for comparisons of vibratory sensory
thresholds.
PMID- 27614185
TI - Involvement of cholecystokinin (CCK) in the daily pattern of gastrointestinal
regulation of Senegalese sole (Solea senegalensis) larvae reared under different
feeding regimes.
AB - Cholecystokinin (CCK) is an important regulator of pancreatic enzyme secretion in
adult mammals and teleosteans. Although some studies have focused on the
interaction between CCK and trypsin in marine fish larvae, little is known about
the circadian patterns of the regulatory mechanism involving these two digestive
components. In this study, we took advantage of the characteristic change from a
diurnal to a nocturnal feeding habit that occurs in Senegalese sole (Solea
senegalensis) post-larvae, to conduct an experiment where larvae and postlarvae
were submitted to three different feeding regimes from mouth opening: continuous
feeding, diurnal feeding and nocturnal feeding. The aim was to establish
different daily feeding scenarios to uncover the operating mechanisms of CCK and
tryptic enzyme activity over the 24-hourcycle to better understand the regulation
of digestion in developing fish larvae. Results show a prevalence of simultaneous
and opposing trends of CCK level and tryptic activity as a function of the
postprandial time. This finding supports the existence of a regulatory loop
between these two digestive components in pre- and post-metamorphic Senegal sole
larvae. In addition, CCK level was also modulated by the gut content, tending to
be lower when the gut is full and higher when is being emptied. Furthermore,
larvae were able to synchronize digestive functions to very different feeding
regimes, although it seems to be important having a diurnal feeding phase during
pre-metamorphic stages for a proper development.
PMID- 27614186
TI - Porous microspheres as promising vehicles for the topical delivery of poorly
soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro
&in vivo.
AB - Asiaticoside is a natural compound possessing diverse pharmacological effects
with great potential for clinical use. However, the low solubility and oil-water
partition coefficient of asiaticoside lead to reduced effect and limited
application. This study aims to construct a porous microsphere for the sustained
release of asiaticoside to improve its absorption and enhance the therapeutic
effects. Parameters of the formulations, including the drug to polymer ratio,
solvent amounts of the inner and external phases, the stirring speed for
preparation, and the drug entrapment efficiency were investigated and optimized.
Particle size, morphology, pores structure, and Fourier transform infrared
spectrum of the microsphere were characterized. The release kinetics and cellular
uptake profiles of the asiaticoside-microspheres were examined. The therapeutic
effects of asiaticoside-microspheres on wound healing and skin appendages
regeneration were investigated in vitro & in vivo. Results showed that the
optimized asiaticoside-microspheres possess spherical spongy structure with
cylindrical holes. Asiaticoside can be loaded in the microsphere with high
efficiency and released with sustained manner. The cellular uptake of
asiaticoside from the microspheres was increased with 9.1 folds higher than that
of free solution. Asiaticoside-microspheres expressed the strong promotion in the
proliferation, migration of keratinocytes and wound scratching healing in vitro.
More importantly, they significantly accelerated the re-epithelization, collagen
synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous
microsphere was shown a novel carrier for the sustained delivery of poorly
soluble asiaticoside, with absorption and therapeutic effects improved.
Asiaticoside-microsphere is a promising topical preparation with excellent
regenerative effects for the wound therapy.
PMID- 27614187
TI - The Clinical Efficacy for Two-Level Transforaminal Epidural Steroid Injections.
AB - BACKGROUND: Epidural steroid injections have been used in combination with other
modalities for the treatment of lumbar radicular pain. The literature has shown
that 1-level lumbar fluoroscopically guided transforaminal epidural steroid
injections (TFESIs) are effective in decreasing pain and morbidity; however, the
efficacy of 2-level TFESIs has not been investigated, although they are performed
by many practitioners in the treatment of lumbar radicular pain. OBJECTIVES: To
assess the clinical effectiveness of 2-level TFESIs in patients with unilateral,
single-level lumbar radicular pain. In addition, a subgroup analysis was
performed based on disk herniation location. STUDY DESIGN: Retrospective cohort.
SETTING: Outpatient physiatry pain practice. PATIENTS: A total of 721 patients
were included in this study having undergone a two-level transforaminal epidural
steroid injection. METHODS: The study group included patients who underwent a 2
level lumbar TFESI. Patients presented for lumbar radicular pain as the result of
disk herniation with or without radiculopathy and were scheduled to receive a
lumbar TFESI at L3 or below. Of this group, only those that underwent a 2-level
TFESIs were included in the study, and data analysis was carried out on this
group. MAIN OUTCOME MEASURES: Subjects were assessed with a pain numerical rating
scale (NRS 0-10) and Oswestry Disability Index (ODI) before TFESI and at 2-week
and 2-month follow-up. Responders were defined as greater that 50% reduction in
NRS or greater than 40% reduction in ODI. RESULTS: A total of 57.7% of patients
were responders in terms of NRS (P < .05, confidence interval 53.6%-61.9%) and
51.7% responded in ODI at 2-month follow-up (P < .05 [confidence interval 47.5%
55.9%]). In addition, patients with complete pain relief (defined as 0/10 on NRS)
were noted at both 2-week (n = 239, 33%) and 2-month (n = 130, 18%) follow-up. In
subgroup analysis, the paracentral/subarticular disk group had an increased
number of responders, 66.0% in NRS and 64.0% in ODI at 2-month follow-up (P <
.05). CONCLUSIONS: Two-level TFESIs are effective in the management of radicular
pain, but more research is needed to evaluate the utility of this treatment
compared with single-level TFESI. Our study showed a greater improvement in pain
and function as a result of 2-level TFESIs in the setting of
paracentral/subarticular disk herniations. LEVEL OF EVIDENCE: IV.
PMID- 27614188
TI - Absence of Pear1 does not affect murine platelet function in vivo.
AB - BACKGROUND: Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a
transmembrane platelet receptor that amplifies the activation of the platelet
fibrinogen receptor (alphaIIbbeta3) during platelet aggregation. In man, Pear1
polymorphisms are associated with changes in platelet aggregability. In this
report, we characterized Pear1 expression and function in murine platelets.
METHODS: Pear1 phosphorylation and signaling, platelet aggregation, alpha
degranulation and clot retraction were studied in WT and Pear1-/- platelets. The
function of Pear1 in haemostasis and thrombosis was studied in a mouse tail vein
bleeding and ferric chloride-induced mesenteric thrombosis model. RESULTS: Mature
murine platelets express Pear1 on their membrane and clustering of Pear1 by anti
Pear1 antibodies triggered platelet aggregation. Pear1 was weakly phosphorylated
during collagen-induced murine platelet aggregation and was translocated to the
cytoskeleton. Absence of murine Pear1 impaired dextran sulfate-induced platelet
aggregation, but did not impact collagen-, AYPGK and ADP-induced platelet
aggregation, coupled to a lower Pear1 expression in murine than in human
platelets and to weaker Pear1-mediated downstream signaling. Neither clot
retraction nor alpha-degranulation was affected in Pear1-/- mice. Likewise, in
vivo tests like the tail vein bleeding time and thrombus formation in mesenteric
veins were similar in WT and Pear1-/- mice. CONCLUSION: Murine platelet Pear1
shares a number of characteristics with human platelet PEAR1. Nevertheless,
murine Pear1 contributes less to platelet function as does human PEAR1 and does
not overtly impact haemostasis and thrombosis in mice.
PMID- 27614189
TI - Pregnancy and non-pregnancy related ovarian vein thrombosis: Clinical course and
outcome.
AB - OBJECTIVE: To collect and summarize demographic, clinical, laboratory and
radiologic characteristics, as well as management and follow-up data, of patients
diagnosed with ovarian vein thrombosis. METHODS: A multicenter retrospective
review of all patients diagnosed with ovarian vein thrombosis between January
2000 and May 2015 at three university hospitals. RESULTS: Data of 74 women were
analyzed. Mean age was 31+/-9years. Sixty (81.1%) cases were pregnancy-related.
The presence of at least one underlying risk factor (most commonly active
infection or surgery) was more common among pregnancy than non-pregnancy related
cases (61.7% vs. 14.3%, P=0.002). Anticoagulation therapy was administered in
98.6% of patients and adjunctive antibiotic therapy in 39 (52.7%). At a median
follow-up of 40+/-38months, only one recurrent thrombotic event was observed, and
no events of death. Median duration of anticoagulation treatment tended to be
longer among patients with non-pregnancy related OVT (6months [3-14] vs. 3months
[3-6], P=0.1). Thrombophilic evaluation detected any thrombophilic risk factor in
12 (20%) and 6 (42.9%) women with pregnancy and non-pregnancy related ovarian
vein thrombosis, respectively (P=0.09). CONCLUSION: Pregnancy-related ovarian
vein thrombosis is characterized by a provoked nature and a high rate of
resolution after short term treatment. Treatment of three months duration of
anticoagulation following this condition appeared in this study to be safe, with
no recurrences encountered during a median follow up of 40months. Thrombophilia
seems to have an important role in ovarian vein thrombosis and should be
evaluated in non-pregnancy related cases.
PMID- 27614190
TI - Structure-activity relationship study of peptidomimetic aldehydes as enterovirus
71 3C protease inhibitors.
AB - A series of peptidomimetic aldehydes were designed, synthesized, and evaluated
for their biochemical activity against 3C protease (3Cpro) and anti-enterovirus
71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC50 = 0.22 +/-
0.07 MUM, EC50 = 0.18 +/- 0.05 MUM) could bind well to the active site of EV71
3Cpro, which was consistent with the biological data compared to reference 5a
(IC50 = 0.54 +/- 0.02 MUM, EC50 = 0.26 +/- 0.07 MUM). Structure and relationship
study led to the discovery of aldehyde 5x (IC50 = 0.10 +/- 0.02 MUM, EC50 = 0.11
+/- 0.07 MUM), which exhibited the most potent 3Cpro inhibitory and antiviral
activity.
PMID- 27614191
TI - Solubility and diffusion of oxygen in phospholipid membranes.
AB - The transport of oxygen and other nonelectrolytes across lipid membranes is known
to depend on both diffusion and solubility in the bilayer, and to be affected by
changes in the physical state and by the lipid composition, especially the
content of cholesterol and unsaturated fatty acids. However, it is not known how
these factors affect diffusion and solubility separately. Herein we measured the
partition coefficient of oxygen in liposome membranes of dilauroyl-, dimiristoyl-
and dipalmitoylphosphatidylcholine in buffer at different temperatures using the
equilibrium-shift method with electrochemical detection. The apparent diffusion
coefficient was measured following the fluorescence quenching of 1
pyrenedodecanoate inserted in the liposome bilayers under the same conditions.
The partition coefficient varied with the temperature and the physical state of
the membrane, from below 1 in the gel state to above 2.8 in the liquid
crystalline state in DMPC and DPPC membranes. The partition coefficient was
directly proportional to the partial molar volume and was then associated to the
increase in free-volume in the membrane as a function of temperature. The
apparent diffusion coefficients were corrected by the partition coefficients and
found to be nearly the same, with a null dependence on viscosity and physical
state of the membrane, probably because the pyrene is disturbing the surrounding
lipids and thus becoming insensitive to changes in membrane viscosity. Combining
our results with those of others, it is apparent that both solubility and
diffusion increase when increasing the temperature or when comparing a membrane
in the gel to one in the fluid state.
PMID- 27614192
TI - Localization of methyl-branched ceramide [EOS] species within the long
periodicity phase in stratum corneum lipid model membranes: A neutron diffraction
study.
AB - The outermost layer of the mammalian skin, the stratum corneum (SC), is a very
thin structure and realizes simultaneously the main barrier properties. The
penetration barrier for xenobiotica is mostly represented by a complex lipid
matrix. There is great interest in the subject of getting information about the
arrangement of the lipids, which are mainly ceramides (CER), free fatty acids
(FFA) and cholesterol (CHOL). SC lipid model membranes containing synthetically
derived lipids in a non-physiological ratio were investigated. To compare the
study to a former experiment, a methyl-branched ceramide [EOS] species in
presence of the ultra-long chain CER[AP], CHOL and behenic acid (23/10/33/33,
wt%) was applied. The membrane structure was studied using the very versatile
technique of neutron diffraction. We were able to identify a long-periodicity
phase (LPP) with a size of 114A or 118A with CER[EOS]-br in a ratio of >60wt% of
the ceramides. Furthermore, we figured out two additional coexisting short
periodicity phases (SPP) with repeat distances of 48A and 45A, respectively.
Partial deuterations of CER[EOS]-br and CER[AP] enabled the localization of the
molecules within the multiphase system. CER[EOS]-d3 was present in the LPP, but
absent in both SPP. CER[AP]-d3 was determined in both short phases but not
localized within the LPP. Besides, we revealed influences of humidity and time
with respect to the long-periodicity phase.
PMID- 27614193
TI - Parental bonds and body dissatisfaction in a clinical sample: The mediating roles
of attachment anxiety and media internalization.
AB - We evaluated an attachment theory model in which mother and father care were
hypothesized to be indirectly related to body dissatisfaction mediated by
attachment anxiety and media internalization. Participants were 232 women
diagnosed with an eating disorder who completed a retrospective measure of
parental bonds, and measures of attachment anxiety, media internalization, and
body image. Mother care was negatively associated with body dissatisfaction,
suggesting that recollection of mothers as less caring was directly related to
poorer body image. Lower father care, was indirectly associated with greater body
dissatisfaction mediated by higher attachment anxiety and higher media
internalization. That is, women with an eating disorder who recollected fathers
as less caring had higher attachment anxiety, which was related to greater
internalizing of media-related thin ideals, that in turn was associated with
poorer body image. Mothers and fathers may impact body dissatisfaction by
differing mechanisms in clinical samples.
PMID- 27614194
TI - Corrigendum to "C-reactive protein levels after cardiac arrest in patients
treated with therapeutic hypothermia" [Resuscitation 85 (2014) 932-938].
PMID- 27614195
TI - Magnetic carboxylated cellulose nanocrystals as adsorbent for the removal of
Pb(II) from aqueous solution.
AB - A novel magnetic carboxylated cellulose nanocrystal composite (CCN-Fe3O4) was
prepared as an adsorbent for the adsorption of Pb(II) from aqueous solution. The
new adsorbent was characterized by transmission electron microscopy, vibrating
sample magnetometry, Fourier-transform infrared spectroscopy, and X-ray
photoelectron spectroscopy. Batch experiments were carried out to investigate the
effects of contact time, adsorbent dose, pH, and temperature on adsorption
capacity. Pb(II) adsorption onto CCN-Fe3O4 reached equilibrium in 240min, and the
maximum adsorption capacity of Pb(II) was 63.78mgg-1 at 298.2K. The equilibrium
data fitted the Langmuir isotherm model better than the Freundlich isotherm
model, and they were well explained in terms of pseudo-second-order kinetics.
Thermodynamics studies indicated that the adsorption of Pb(II) onto CCN-Fe3O4 was
spontaneous and endothermic in nature. The adsorbent could also be regenerated
with acid treatment and successfully reapplied.
PMID- 27614196
TI - Resveratrol cross-linked chitosan loaded with phospholipid for controlled release
and antioxidant activity.
AB - Despite the therapeutic effects of resveratrol, its clinical application is
restricted by its poor oral bioavailability and low water solubility. To overcome
these physicochemical and pharmacokinetic limitations, encapsulation of
resveratrol (RV) into nanodevices has been explored. Resveratrol cross-linked
chitosan nanoparticles modified with phospholipids (RVC-lipid) were synthesized
using a double emulsion technique. The surface morphology of RVC-lipid
nanoparticles was evaluated with field emission scanning electron microscopy
(FESEM) and transmission electron microscopy (TEM). Particle size was measured
using dynamic light scattering technique (DLS), X-ray diffraction (XRD) was
performed to identify the crystallographic nature and Fourier transform infrared
spectroscopy (FTIR) was used to measure changes in the chemical structures of the
resveratrol and RVC-lipid nanoparticles. Results showed RVC-lipid nanoparticle
had a characteristic amorphous structure, a mean particle sizes of 570nm in DI
water and 950nm in ethanol, and an encapsulation efficiency of 63.82% in aqueous
medium and 85.59% in ethanol medium. In-vitro release studies demonstrated a slow
and sustained release of resveratrol governed by diffusion. Based on assays of
antioxidant activity the scavenging activity of RVC-lipid nanoparticles was
inferior to that of resveratrol due to its prolonged release. We concluded that
phospholipids are the potential carriers for resveratrol.
PMID- 27614197
TI - Application of two-phase lamellar model to study the ultrastructure of annealed
canna starch: A comparison with linear correlation function.
AB - Canna starch was annealed at sub-gelatinization temperature (50 degrees C) with
different annealing time. Small angle X-ray scattering (SAXS) was used to
estimate the ultrastructure of the annealed starches with the combined two-phase
lamellar model and one-dimensional correlation function. The results showed that,
upon annealing, water preferably swelled the amorphous regions of canna starch
granules while maintained the part of crystalline region, resulted in an increase
in amorphous thickness (da) and lamellar repeat distance (d). Power law plots
indicates that a mass fractal (self-similar) structure was observed in canna
starch, and annealing induces a less compact structure compared to native canna
starch (NCS). Correlation analysis showed that no correlation was existed between
annealing time and lamellar peak area, width of peak, and volume crystallinity.
However, due to the initial degradation of the amorphous region, the volume
crystallinity increased significantly with the increase of crystalline thickness
(dc).
PMID- 27614198
TI - Information persistence evaluated with low-density dot patterns.
AB - After more than a century of study, we do not yet fully understand how shapes and
patterns are encoded and identified. Greater progress might result from
quantifying stimulus information, thus allowing manipulation of the degree to
which a shape or pattern can elicit recognition. The present work used discrete
dot patterns that are seen as letters of the alphabet. By adjusting the density
of the dots in each pattern, one can determine the probability that it will be
recognized. The experiments displayed low-density dot patterns to human
respondents, assessing the interval across which non-redundant information
provided by two compatible subsets would combine to elicit recognition. This
provided a measure of the time required for decay of information persistence.
Viewed in the context of prior work, the evidence indicates that the retina
mediates initial visibility of the stimulus trace, but the longer-duration
persistence required for memory retrieval is mediated by visual cortex.
PMID- 27614200
TI - Analysis of liver damage from radon, X-ray, or alcohol treatments in mice using a
self-organizing map.
AB - In our previous studies, we found that low-dose radiation inhibits oxidative
stress-induced diseases due to increased antioxidants. Although these effects of
low-dose radiation were demonstrated, further research was needed to clarify the
effects. However, the analysis of oxidative stress is challenging, especially
that of low levels of oxidative stress, because antioxidative substances are
intricately involved. Thus, we proposed an approach for analysing oxidative liver
damage via use of a self-organizing map (SOM)-a novel and comprehensive technique
for evaluating hepatic and antioxidative function. Mice were treated with radon
inhalation, irradiated with X-rays, or subjected to intraperitoneal injection of
alcohol. We evaluated the oxidative damage levels in the liver from the SOM
results for hepatic function and antioxidative substances. The results showed
that the effects of low-dose irradiation (radon inhalation at a concentration of
up to 2000 Bq/m3, or X-irradiation at a dose of up to 2.0 Gy) were comparable
with the effect of alcohol administration at 0.5 g/kg bodyweight. Analysis using
the SOM to discriminate small changes was made possible by its ability to 'learn'
to adapt to unexpected changes. Moreover, when using a spherical SOM, the method
comprehensively examined liver damage by radon, X-ray, and alcohol. We found that
the types of liver damage caused by radon, X-rays, and alcohol have different
characteristics. Therefore, our approaches would be useful as a method for
evaluating oxidative liver damage caused by radon, X-rays and alcohol.
PMID- 27614199
TI - Effects of long-term endocrine disrupting compound exposure on Macaca mulatta
embryonic stem cells.
AB - Endocrine disrupting chemicals (EDCs) exert significant effects on health and
physiology, many traceable to effects on stem cell programming underlying
development. Understanding risk of low-level, chronic EDC exposure will be
enhanced by knowledge of effects on stem cells. We exposed rhesus monkey
embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine
(ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl)
phthalate (DEHP)] for 28days, and evaluated effects on gene expression by RNAseq
transcriptome profiling. We observed little effect of BPA, and small numbers of
affected genes (<=119) with other EDCs. There was substantial overlap in effects
across two, three, or four treatments. Ingenuity Pathway analysis indicated
suppression of cell survival genes and genes downstream of several stress
response mediators, activation of cell death genes, and modulations in several
genes regulating pluripotency, differentiation, and germ layer development.
Potential adverse effects of these changes on development are discussed.
PMID- 27614202
TI - Immune and inflammatory responses to freediving calculated from leukocyte gene
expression profiles.
AB - Freedivers hold their breath while diving, causing blood oxygen levels to
decrease (hypoxia) while carbon dioxide increases (hypercapnia). Whereas blood
gas changes are presumably involved in the progression of respiratory diseases,
less is known about their effect on healthy individuals. Here we have used gene
expression profiling to analyze elite athletes' immune and inflammatory responses
to freediving. Blood was collected before and 1 and 3 h after a series of maximal
dynamic and static freediving apneas in a pool, and peripheral blood gene
expression was mapped on genome-wide microarrays. Fractions of phenotypically
distinct immune cells were computed by deconvolution of the gene expression data
using Cibersort software. Changes in gene activity and associated biological
pathways were determined using R and GeneGo software. The results indicated a
temporary increase of neutrophil granulocytes, and a decrease of cytotoxic
lymphocytes; i.e., CD8+ T cells and resting NK cells. Biological pathway
associations indicated possible protective reactions: genes involved in anti
inflammatory responses to proresolving lipid mediators were upregulated, whereas
central factors involved in granule-mediated lymphocyte cytotoxicity were
downregulated. While it remains unresolved whether freediving alters the immune
system's defensive function, these results provide new insight into leukocyte
responses and the protection of homeostasis in healthy athletes.
PMID- 27614201
TI - Neutron relative biological effectiveness in Hiroshima and Nagasaki atomic bomb
survivors: a critical review.
AB - The calculated risk of cancer in humans due to radiation exposure is based
primarily on long-term follow-up studies, e.g. the life-span study (LSS) on
atomic bomb (A-bomb) survivors in Hiroshima and Nagasaki. Since A-bomb radiation
consists of a mixture of gamma-rays and neutrons, it is essential that the
relative biological effectiveness (RBE) of neutrons is adequately evaluated if a
study is to serve as a reference for cancer risk. However, the relatively small
neutron component hampered the direct estimation of RBE in LSS data. To
circumvent this problem, several strategies have been attempted, including dose
independent constant RBE, dose-dependent variable RBE, and dependence on the
degrees of dominance of intermingled gamma-rays. By surveying the available
literature, we tested the chromosomal RBE of neutrons as the biological endpoint
for its equivalence to the microdosimetric quantities obtained using a tissue
equivalent proportional counter (TEPC) in various neutron fields. The radiation
weighting factor, or quality factor, Qn, of neutrons as expressed in terms of the
energy dependence of the maximum RBE, RBEm, was consistent with that predicted by
the TEPC data, indicating that the chromosomally measured RBE was independent of
the magnitude of coexisting gamma-rays. The obtained neutron RBE, which varied
with neutron dose, was confirmed to be the most adequate RBE system in terms of
agreement with the cancer incidence in A-bomb survivors, using chromosome
aberrations as surrogate markers. With this RBE system, the cancer risk in A-bomb
survivors as expressed in unit dose of reference radiation is equally compatible
with Hiroshima and Nagasaki cities, and may be potentially applicable in other
cases of human radiation exposure.
PMID- 27614206
TI - Editorial overview: Molecular Imaging Section.
PMID- 27614204
TI - Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary
artery disease.
AB - Recent genetic studies have revealed an association between polymorphisms at the
ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies
have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7
maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested
whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in
patients with established CAD. A cohort of 1,128 patients with angiographic
proven CAD, who were followed up prospectively for a mean follow-up period of 63
(range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox
regression) compared heterozygous (AG) and wild-type (AA) with the reference
homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to
ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were
heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only
16.2% were homozygous for the GG genotype. During the follow-up period, 109
(9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA
genotype was an independent risk factor for CV mortality compared with reference
genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated
survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for
AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was
associated with improved CV survival in patients with documented CAD. The native
overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to
neointimal thickening, atherosclerosis progression and acute plaque events.
ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic
and therapeutic goals.
PMID- 27614203
TI - A synthetic luciferin improves in vivo bioluminescence imaging of gene expression
in cardiovascular brain regions.
AB - Bioluminescence imaging is an effective tool for in vivo investigation of
molecular processes. We have demonstrated the applicability of bioluminescence
imaging to spatiotemporally monitor gene expression in cardioregulatory brain
nuclei during the development of cardiovascular disease, via incorporation of
firefly luciferase into living animals, combined with exogenous d-luciferin
substrate administration. Nevertheless, d-luciferin uptake into the brain tissue
is low, which decreases the sensitivity of bioluminescence detection,
particularly when considering small changes in gene expression in tiny central
areas. Here, we tested the hypothesis that a synthetic luciferin, cyclic
alkylaminoluciferin (CycLuc1), would be superior to d-luciferin for in vivo
bioluminescence imaging in cardiovascular brain regions. Male C57B1/6 mice
underwent targeted delivery of an adenovirus encoding the luciferase gene
downstream of the CMV promoter to the subfornical organ (SFO) or paraventricular
nucleus of hypothalamus (PVN), two crucial cardioregulatory neural regions. While
bioluminescent signals could be obtained following d-luciferin injection (150
mg/kg), CycLuc1 administration resulted in a three- to fourfold greater
bioluminescent emission from the SFO and PVN, at 10- to 20-fold lower substrate
concentrations (7.5-15 mg/kg). This CycLuc1-mediated enhancement in
bioluminescent emission was evident early following substrate administration
(i.e., 6-10 min) and persisted for up to 1 h. When the exposure time was reduced
from 60 s to 1,500 ms, minimal signal in the PVN was detectable with d-luciferin,
whereas bioluminescent images could be reliably captured with CycLuc1. These
findings demonstrate that bioluminescent imaging with the synthetic luciferin
CycLuc1 provides an improved physiological genomics tool to investigate molecular
events in discrete cardioregulatory brain nuclei.
PMID- 27614207
TI - Editorial overview: Chemical genetics and epigenetics.
PMID- 27614205
TI - Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates
widespread neuropathology.
AB - Pompe disease, caused by deficiency of acid alpha-glucosidase (GAA), leads to
widespread glycogen accumulation and profound neuromuscular impairments. There
has been controversy, however, regarding the role of central nervous system
pathology in Pompe motor dysfunction. We hypothesized that absence of GAA protein
causes progressive activation of neuropathological signaling, including pathways
associated with cell death. To test this hypothesis, genomic data (Affymetrix
Mouse Gene Array 2.0ST) from the midcervical spinal cord in 6 and 16 mo old Pompe
(Gaa-/-) mice were evaluated (Broad Institute Molecular Signature Database),
along with spinal cord histology. The midcervical cord was selected because it
contains phrenic motoneurons, and phrenic-diaphragm dysfunction is prominent in
Pompe disease. Several clinically important themes for the neurologic etiology of
Pompe disease emerged from this unbiased genomic assessment. First, pathways
associated with cell death were strongly upregulated as Gaa-/- mice aged, and
motoneuron apoptosis was histologically verified. Second, proinflammatory
signaling was dramatically upregulated in the Gaa-/- spinal cord. Third, many
signal transduction pathways in the Gaa-/- cervical cord were altered in a manner
suggestive of impaired synaptic function. Notably, glutamatergic signaling
pathways were downregulated, as were "synaptic plasticity pathways" including
genes related to neuroplasticity. Fourth, many genes and pathways related to
cellular metabolism are dysregulated. Collectively, the data unequivocally
confirm that systemic absence of GAA induces a complex neuropathological cascade
in the spinal cord. Most importantly, the results indicate that Pompe is a
neurodegenerative condition, and this underscores the need for early therapeutic
intervention capable of targeting the central nervous system.
PMID- 27614208
TI - Species variation and spatial differences in mucin expression from corneal
epithelial cells.
AB - Mucins are large glycoproteins expressed by epithelial cells of both the
conjunctiva and cornea, and principle components of the glycocalyx. They are
thought to play an important role in determining the interactions between the
cornea/conjunctiva and the overlying tear film. The purpose of this study was to
characterize the membrane-associated corneal mucin expression pattern from
multiple species commonly used in ophthalmic research and drug development to
better define the biochemical attributes of the ocular surface. Humans, rhesus
macaques and dogs were found to have a very similar pattern of mucin expression,
with mucin 16 (MUC16) being the most prevalent mucin transcript. In contrast, the
rabbit had a unique mucin expression pattern with all mucin transcripts expressed
at relatively similar levels. To determine if there were spatial differences in
expression, peripheral and central corneal epithelium were individually isolated
and evaluated for mucin expression. In all species examined, MUC1, MUC4 and MUC16
had higher peripheral corneal expression when compared with central, which
reached statistical significance in MUC1 (rhesus and dog). The data demonstrated
variation in corneal epithelial membrane-associated mucin expression between
species, with the rabbit having a distinct expression pattern. These differences
may be reflective of the environment, pathogen exposure or tear film dynamics of
the respective species. The species differences, as well as regional mucin
expression patterns, characterized in this study further define the biochemical
composition of the ocular surface and may play an important role in tear film
stability.
PMID- 27614210
TI - A Case of Possible Iatrogenic Ketamine-Induced Mania in a Patient Being Treated
for Postoperative Pain.
PMID- 27614209
TI - Retargeting of herpes simplex virus (HSV) vectors.
AB - Gene therapy applications depend on vector delivery and gene expression in the
appropriate target cell. Vector infection relies on the distribution of natural
virus receptors that may either not be present on the desired target cell or
distributed in a manner to give off-target gene expression. Some viruses display
a very limited host range, while others, including herpes simplex virus (HSV),
can infect almost every cell within the human body. It is often an advantage to
retarget virus infectivity to achieve selective target cell infection.
Retargeting can be achieved by (i) the inclusion of glycoproteins from other
viruses that have a different host-range, (ii) modification of existing viral
glycoproteins or coat proteins to incorporate peptide ligands or single-chain
antibodies (scFvs) that bind to the desired receptor, or (iii) employing soluble
adapters that recognize both the virus and a specific receptor on the target
cell. This review summarizes efforts to target HSV using these three strategies.
PMID- 27614211
TI - Modulation of sweet preference by the actual and anticipated consequences of
eating.
AB - Previous research has shown that non-human animals exhibit an inverted-U pattern
of sweet preference, with consumption increasing across moderate levels of
sweetness and then declining for high levels of sweetness. In rodents, this
pattern reflects an avoidance of the postingestive effects of consuming energy
dense sugar solutions (conditioned satiation). Here, we examined whether humans
also adjust their preferences to compensate for the anticipated energy
content/satiating outcomes of consuming sweetened foods. In two experiments (each
N = 40), participants were asked to taste and imagine eating small (15 g) and
large (250 g) portions of five novel desserts that varied in sweetness.
Participants evaluated the desserts' expected satiety, expected satiation, and
expected sickliness. A measure of estimated energy content was also derived using
a computerized energy compensation test. This procedure was completed before and
after consuming a standard lunch. Across both experiments, results confirmed that
participants preferred a less sweet dessert when asked to imagine eating a large
versus a small portion, and when rating the dessert in a fed versus fasted state.
We also obtained evidence that participants anticipated more energy from the
sweeter desserts (even in Experiment 2 when half of the participants were
informed that the desserts were equated for energy content). However we found
only partial evidence for anticipated satiation-expected sickliness was related
systematically to increases in sweetness, but expected satiation and expected
satiety were only weakly influenced. These findings raise questions about the
role of sweetness in the control of food intake (in humans) and the degree to
which 'sweet-calorie learning' occurs in complex dietary environments where
sweetness may actually be a poor predictor of the energy content of foods.
PMID- 27614212
TI - Adolescents' perspectives on food literacy and its impact on their dietary
behaviours.
AB - Food literacy has been identified as a promising approach to support healthy
dietary behaviours in adolescents. However, adolescents' perspectives on food
literacy and the impact it could have on their dietary behaviours are not well
understood. This study explored adolescents' perspectives on the potential for
food literacy to influence their dietary behaviours. Fifteen focus groups were
conducted with adolescents aged 12-17 years and encompassed quantitative and
qualitative questions. Adolescents were asked to rank 22 aspects of food literacy
in order of importance and discuss their responses as a group. Overall,
adolescents ranked food and nutrition knowledge as more important than food
skills and food capacity. Although adolescents stated that food and nutrition
knowledge is important for them to eat well, the majority did not apply their
knowledge to practice due to low confidence in food skills. Participants
demonstrated very limited knowledge about macro aspects of food literacy such as
animal welfare or environmental sustainability. Food skills such as planning and
managing budgets for food and time for food shopping were ranked as least
important due to being presently irrelevant but recognised as important later in
life. Adolescents reported being very interested in developing food skills such
as food preparation but they had very limited opportunities due to lack of food
literacy education in home and high school settings. The high school setting
provides an ideal opportunity for adolescents to improve their food literacy in
particular food skills through home economics. Future research should develop and
measure adolescents' food literacy and its impact on their dietary behaviours.
PMID- 27614213
TI - Histone deacetylases inhibitors (HDACis) as novel therapeutic application in
various clinical diseases.
AB - Accumulating evidence suggests that histone hypoacetylation which is partly
mediated by histone deacetylase (HDAC), plays a causative role in the etiology of
various clinical disorders such as cancer and central nervous diseases. HDAC
inhibitors (HDACis) are natural or synthetic small molecules that can inhibit the
activities of HDACs and restore or increase the level of histone acetylation,
thus may represent the potential approach to treating a number of clinical
disorders. This manuscript reviewed the progress of the most recent experimental
application of HDACis as novel potential drugs or agents in a large number of
clinical disorders including various brain disorders including neurodegenerative
and neurodevelopmental cognitive disorders and psychiatric diseases like
depression, anxiety, fear and schizophrenia, and cancer, endometriosis and cell
reprogramming in somatic cell nuclear transfer in human and animal models of
disease, and concluded that HDACis as potential novel therapeutic agents could be
used alone or in adjunct to other pharmacological agents in various clinical
diseases.
PMID- 27614215
TI - Direct bilirubin in clinical practice - Interpretation and haemolysis
interference guidance reassessed.
AB - OBJECTIVE: Diagnosis of hyperbilirubinaemia may rely on direct bilirubin (DBIL)
measurement. Specimen suitability for DBIL depends on the degree of haemolysis
present and method specifications. Our study reassesses the empiric, syncretised
haemolysis guidance for DBIL measurement. METHODS: Diazo and vanadate-oxidation
assays for DBIL are compared, using sera from adults and neonates. Subsequent
data analyses and statistics guide our conclusions on the clinical utility of
haemolysed sera. RESULTS: 48% Patients' specimens had haemolysis exceeding the
diazo-DBIL assay's specified haemolysis limit, thus generating 'specimen
unsuitable' comment on clinical reports. Our linearity study shows a diazo-DBIL
bias of up to 21MUmol/L in diluted specimens, regardless of grade of haemolysis.
Haemolysed patients' serum gives unpredictably biased diazo-DBIL results relative
to results from vanadate-oxidation method. The pleiotropy of effect includes
negative, negligible, and positive bias; a greater bias is apparent when albumin
is <37g/L. Predominant unconjugated hyperbilirubinaemia is defined as the 90th
percentile D/TBIL limit of <36%, mixed hyperbilirubinaemia by D/TBIL 36-60%, and
mainly conjugated hyperbilirubinaemia when D/TBIL is >60%. CONCLUSIONS:
Haemolysed diazo-DBIL result is unsuitable for clinical use, due to
unpredictability of observed bias. Our data shows that current haemolysis
guidance is inaccurate and in need of revision. There is no direct association
between haemolysis and diazo-DBIL results. Notwithstanding haemolysis, type of
assay, and low albumin concentration, our study show D/TBIL% facilitates
detection of the nature of hyperbilirubinaemia present. In addition, laboratories
have an option to select a more befitting assay, such as the vanadate-oxidation
method as it is unaffected by haemolysis.
PMID- 27614214
TI - A case of Bacteroides pyogenes bacteremia secondary to liver abscess.
AB - Bacteroides pyogenes, a non-spore-forming, anaerobic, gram-negative rod, is a
component of the oral flora of animals and has, on occasion, been reported to
cause human infection through dog or cat bites. We report the first case of B.
pyogenes bacteremia secondary to liver abscess with no history of an animal bite.
The microorganism was identified by 16S rRNA sequencing.
PMID- 27614216
TI - Critical pre-examination variables in the hemostasis laboratory and their quality
indicators.
AB - The total testing process comprises a number of phases of laboratory testing,
which can be broadly considered as comprising pre-examination, examination and
post-examination activities. Although each phase is crucial to providing accurate
and meaningful laboratory results, the pre-examination phase of testing is where
most laboratory errors currently occur, and thus requires special attention. The
activities in this phase include sample collection, handling, transportation,
processing and storage, which are frequently outside the control of the
laboratory performing the tests. Samples for hemostasis testing are particularly
vulnerable to pre-analytical variables, which may ultimately lead to
inappropriate test results. We outline here several strategies to mitigate
potential problems in the pre-examination phase. We also recommend the
implementation of several processes to reduce errors.
PMID- 27614217
TI - Sample-dependent diagnostic accuracy of prostaglandin D synthase in cerebrospinal
fluid leak.
AB - BACKGROUND: Prostaglandin D2 synthase, commonly known as beta-trace protein
(betaTP), is an excellent biomarker for the assessment of cerebrospinal fluid
(CSF) leaks. Despite being widely used, the limits for the diagnostic values of
betaTP are not well established to date, and currently suggested cut-off values
in literature range from 0.25 to 6.0mg/L. Sample-specific and more accurate
thresholds are a current need. METHODS: A retrospective observational study,
performed in a tertiary-care hospital, between January 2006 and January 2014. A
total of 74 patients were included, with a definitive diagnosis after initial
leak suspicion and at least one determination of betaTP using a nephelometry
based assay. A total of 46 CSF samples were included in the control group.
Samples were obtained from nasal secretions, ear secretions or spinal surgical
injury, directly using sterile Eppendorf tubes. The analysis of 3 different cut
off values was performed and the receiver operating curve (ROC) analyses were
calculated. RESULTS: Initial diagnostic suspicion was confirmed in 51% of cases,
most of which were of postoperative origin (51%) and traumatic (26%). The betaTP
median concentration in different samples was significantly higher in the
presence of cerebrospinal fluid fistula, regardless of sample type (22.0mg/L vs.
0.24mg/L, 95% confidence interval: 19.0-30.8 vs. 0.08-0.40; p<0.001). Data from
contingency tables show 100% sensitivity and specificity, depending on sample
type and the cut-off value used: for rhinorrhea and otorrhea samples, the most
appropriate it was 0.7mg/L, while values >2.0mg/L could be used for spine
postoperative fluid leakage samples. CONCLUSIONS: The cut off value for betaTP in
the diagnosis and follow-up of cerebrospinal fluid leaks should be modified
depending on the type of secretion (sample type), for a better diagnostic
accuracy.
PMID- 27614218
TI - Characterization of serological neo-epitope biomarkers reflecting collagen
remodeling in clinically stable chronic obstructive pulmonary disease.
AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by
chronic inflammation that leads to excessive remodeling of the lung extracellular
matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the
blood. Serological markers assessing this have previously been associated with
exacerbations of COPD. However, characterization of these in individuals with
clinically stable COPD is lacking. The aim of this study was to characterize the
collagen remodeling in stable COPD by the serological assessment of neo-epitopes.
DESIGN AND METHODS: Sixty-eight subjects with clinically stable COPD were
included into the study at baseline, and 27 came back for a four weeks follow-up
visit. Serum and plasma levels of neo-epitopes were assessed for the evaluation
of collagen type III (C3M), IV (C4M, C4Ma3, P4NP 7S), and VI (C6M, Pro-C6)
remodeling. RESULTS: C3M, C4M, C4Ma3, P4NP 7S, and C6M levels were significantly
elevated in COPD subjects compared with healthy controls (p<0.0001 to p=0.044).
Each neo-epitope biomarker was significantly correlated between serum and plasma
(p<0.0001) and most biomarkers were stable in the majority of patients from
baseline to week four. Serum C6M levels were weakly correlated with FEV1%
predicted (r=-0.274, p=0.025) and serum Pro-C6 levels were elevated in subjects
with previous exacerbations (p=0.014). C3M, C4Ma3, C6M, and P4NP 7S were weakly
correlated with MRC dyspnea scores (p<0.01). No associations were seen with BMI,
smoking, duration of COPD, blood oxygen saturation, shuttle walk test distance,
GOLD grades, or CAT scores. CONCLUSIONS: Serological biomarkers of collagen
remodeling were elevated in subjects with COPD as compared with healthy
individuals. Biomarker levels were significantly correlated with measures of
dyspnea, indicating a relationship with degree of symptoms, while only C6M showed
a weak but significant association with lung function. Biomarker levels were not
related to GOLD grades, which was in line with previous studies indicating that
ECM remodeling may be related to disease activity rather than severity.
PMID- 27614219
TI - Normal amino-terminal pro-brain natriuretic peptide (NT-proBNP) values in
amniotic fluid.
AB - INTRODUCTION: Brain natriuretic peptide (BNP) is synthesized by human fetal
membranes, both the amnion and chorion. This locally produced BNP inhibits the
contraction of the human myometrium, contributing to the maintenance of
myometrial quiescence during pregnancy. Reference values for NT-proBNP
concentrations in amniotic fluid at different gestational ages have not been
completely defined. We aimed to investigate the range of fetal NT-proBNP values
in amniotic fluid in normal pregnancy between 17 and 41weeks of gestation.
METHODS: Samples of amniotic fluid were obtained from women meeting the following
inclusion criteria: gestational age defined by early ultrasound, singleton
gestation and not in labor. The exclusion criteria were as follows: multiple
gestation, clinically evident chorioamnionitis, laboratory signs of infection in
the amniotic fluid sample and fetal conditions that may alter NT Pro-BNP levels
(anemia, hydrops, etc.). NT-proBNP concentrations in amniotic fluid were measured
using the automated Elecsys(r) proBNP assay. RESULTS: We analyzed 218 samples of
amniotic fluid at various gestational ages. Half of the samples were obtained by
amniocentesis (118 samples), and the other half (100 samples) were obtained by
direct puncture at the time of cesarean section. We found a significant decline
in NT-proBNP concentrations with advancing gestational age. DISCUSSION:
Gestational age has to be taken into consideration in the assessment of NT-proBNP
values. Our data may be used as reference values in fetal medicine, as a possible
predictor of preterm delivery risk using the inferior limit (0.5 multiples of the
median (MoM)) of our normal curve.
PMID- 27614220
TI - Nicotinic acid inhibits NLRP3 inflammasome activation via SIRT1 in vascular
endothelial cells.
AB - Emerging evidences indicated that NLRP3 inflammasome initiates inflammatory
response involved in cardiovascular disease. Nicotinic acid (NA) has been known
to possess potential anti-inflammatory property. The aim of this study was to
investigate the effect of NA on the activation of NLRP3 inflammasome and the
underlying mechanisms. It was found that lipopolysaccharide (LPS) and adenosine
triphosphate (ATP) triggered the activation of NLRP3 inflammasome in human
umbilical vein endothelial cells (HUVECs). NA inhibited NLRP3 inflammasome
activation and subsequent caspase-1 cleavage as well as interleukin (IL)-1beta
secretion. Moreover, NA administration up-regulated SIRT1 expression in HUVECs
stimulated with LPS plus ATP. Importantly, knockdown of SIRT1 reversed the
inhibitory effect of NA on the activation of NLRP3 inflammasome. Further study
revealed that NA also decreased the generation of reactive oxygen species (ROS)
in HUVECs. In addition, NA inhibited NLRP3 inflammasome activation partly through
suppression of ROS. Taken together, these findings indicate that NA is able to
regulate the activation of NLRP3 inflammasome in HUVECs, which may be partly
mediated by SIRT1 and ROS.
PMID- 27614222
TI - Concomitant multiple sclerosis and another autoimmune disease: Does the clinical
course change?
AB - OBJECTIVES: Multiple Sclerosis is a demyelinating disease that can cause
different symptoms by the autoimmune involvement of myelin. CD4+ and CD8+ T-cells
as well as B-cells play important roles in MS pathophysiology. Co-existence of
other autoimmune diseases and multiple sclerosis has been reported previously in
the literature. It is not clear whether this co-existence may change the clinical
course of MS or not. In this study we aim to evaluate the prevalence of other
autoimmune diseases among patients with MS and if they may play any role in the
clinical course of the patients. PATIENTS AND METHODS: Twenty four patients with
multiple sclerosis and another simultaneous autoimmune disease were detected
among 1700 patients referred to the MS clinic of Sina Hospital during two years.
Sex, age, duration of MS and the autoimmune disease as well as the type of the
latter were recorded. For evaluation of disease progression a control group was
randomly selected from the same patients referred to the clinic. EDSS was
measured and recorded in both groups. RESULTS: The prevalence of concomitant
autoimmune disease and multiple sclerosis was 0.014. The mean age of the patients
was 35.04+/-6.45years. There were 18 different autoimmune diseases in the first
group. The mean duration of MS and concomitant autoimmune disease were 5.91 and
9.80+/-7.1years respectively. The mean of EDSS in these patients was 1.62+/-1.12
and in the control group was 3.33+/-1.89. One patient had developed secondary
progressive course in the first group. The statistical difference between these
groups based on EDSS, was significant (P-value: <0.001). The median of EDSS in
the first group was 1.5 and in the second one was 2.5. The mean of annual relapse
rate in the first group was 0.60 and in the second one was 0.62 (P-value: 0.71).
CONCLUSION: The present study shows that several other autoimmune diseases may
coexist with MS and their presence may modify the course of the disease. This
should be re-evaluated in multicenter prospective long term studies.
PMID- 27614221
TI - Adolescent oxycodone self administration alters subsequent oxycodone-induced
conditioned place preference and anti-nociceptive effect in C57BL/6J mice in
adulthood.
AB - : Adolescent and young adult abuse of short-acting MOP-r agonists such as
oxycodone is a pressing public health issue. Few preclinical studies have
examined how adolescent exposure to oxycodone impacts its effects in the
transition to adulthood. OBJECTIVE: To determine in mice how chronic adolescent
oxycodone self-administration (SA) affects subsequent oxycodone-induced
conditioned place preference (CPP), locomotor activity, and anti-nociception once
mice reach early adulthood. METHODS: Adolescent C57BL/6J male mice (4 weeks old,
n = 6-11) and adult mice (10 weeks old, n = 6-10) were surgically implanted with
indwelling jugular catheters. Mice then acquired oxycodone self-administration
(14 consecutive 2-hr daily sessions; 0.25 mg/kg/infusion) followed by a 14-day
drug-free (withdrawal) period in home cage. After the 14-day drug-free period,
mice underwent a 10-day oxycodone CPP procedure (0, 1, 3, 10 mg/kg i.p.) or were
tested for acute oxycodone-induced antinociception in the hot plate assay (3.35,
5, 7.5 mg/kg i.p.). RESULTS: Mice that self-administered oxycodone during
adolescence exhibited greater oxycodone-induced CPP (at the 3 mg/kg dose) than
their yoked saline controls and mice that self-administered oxycodone during
adulthood. Oxycodone dose-dependently increased locomotor activity, but
sensitization developed only to the 3 mg/kg in the mice that underwent oxycodone
self-administration as adolescents. Mice that self-administered oxycodone as
adolescents decreased in the anti-nociceptive effects of oxycodone in one dose (5
mg/kg), whereas animals that self-administered oxycodone as adults did not show
this effect. CONCLUSION: Chronic adolescent oxycodone self-administration led to
increased oxycodone-induced CPP (primarily 1 and 3 mg/kg, i.p.) and reduced
antinociceptive effect of oxycodone (5 mg/kg, i.p.) in adulthood.
PMID- 27614223
TI - Catalase-dependent H2O2 consumption by cardiac mitochondria and redox-mediated
loss in insulin signaling.
AB - We have recently demonstrated that catalase content in mouse cardiac mitochondria
is selectively elevated in response to high dietary fat, a nutritional state
associated with oxidative stress and loss in insulin signaling. Catalase and
various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the
consumption of H2O2 Catalase, located primarily within peroxisomes and to a
lesser extent mitochondria, has a low binding affinity for H2O2 relative to
glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase
to mitochondrial H2O2 consumption is not well understood. In the current study,
using highly purified cardiac mitochondria challenged with micromolar
concentrations of H2O2, we found that catalase contributes significantly to
mitochondrial H2O2 consumption. In addition, catalase is solely responsible for
removal of H2O2 in nonrespiring or structurally disrupted mitochondria. Finally,
in mice fed a high-fat diet, mitochondrial-derived H2O2 is responsible for
diminished insulin signaling in the heart as evidenced by reduced insulin
stimulated Akt phosphorylation. While elevated mitochondrial catalase content
(~50%) enhanced the capacity of mitochondria to consume H2O2 in response to high
dietary fat, the selective increase in catalase did not prevent H2O2-induced loss
in cardiac insulin signaling. Taken together, our results indicate that
mitochondrial catalase likely functions to preclude the formation of high levels
of H2O2 without perturbing redox-dependent signaling.
PMID- 27614224
TI - Hyperaldosteronism induces left atrial systolic and diastolic dysfunction.
AB - Patients with hypertension and hyperaldosteronism show an increased risk of
stroke compared with patients with essential hypertension. Aim of the study was
to assess the effects of aldosterone on left atrial function in rats as a
potential contributor to thromboembolism. Osmotic mini-pumps delivering 1.5 MUg
aldosterone/h were implanted in rats subcutaneously (Aldo, n = 39; controls, n =
38). After 8 wk, left ventricular pressure-volume analysis of isolated working
hearts was performed, and left atrial systolic and diastolic function was also
assessed by atrial pressure-diameter loops. Moreover, left atrial myocytes were
isolated to investigate their global and local Ca2+ handling and contractility.
At similar heart rates, pressure-volume analysis of isolated hearts and in vivo
hemodynamic measurements revealed neither systolic nor diastolic left ventricular
dysfunction in Aldo. In particular, atrial filling pressures and atrial size were
not increased in Aldo. Aldo rats showed a significant reduction of atrial late
diastolic A wave, atrial active work index, and increased V waves. Consistently,
in Aldo rats, sarcomere shortening and the amplitude of electrically evoked
global Ca2+ transients were substantially reduced. Sarcoplasmic reticulum-Ca2+
content and fractional Ca2+ release were decreased, substantiated by a reduced
sarcoplasmic reticulum calcium ATPase activity, resulting from a reduced CAMKII
evoked phosphorylation of phospholamban. Hyperaldosteronism induced atrial
systolic and diastolic dysfunction, while atrial size and left ventricular
hemodynamics, including filling pressures, were unaffected in rats. The described
model suggests a direct causal link between hyperaldosteronism and decreased
atrial contractility and diastolic compliance.
PMID- 27614227
TI - Reduced mitochondrial respiration in the ischemic as well as in the remote
nonischemic region in postmyocardial infarction remodeling.
AB - Scarring and remodeling of the left ventricle (LV) after myocardial infarction
(MI) results in ischemic cardiomyopathy with reduced contractile function.
Regional differences related to persisting ischemia may exist. We investigated
the hypothesis that mitochondrial function and structure is altered in the
myocardium adjacent to MI with reduced perfusion (MIadjacent) and less so in the
remote, nonischemic myocardium (MIremote). We used a pig model of chronic
coronary stenosis and MI (n = 13). Functional and perfusion MR imaging 6 wk after
intervention showed reduced ejection fraction and increased global wall stress
compared with sham-operated animals (Sham; n = 14). Regional strain in MIadjacent
was reduced with reduced contractile reserve; in MIremote strain was also reduced
but responsive to dobutamine and perfusion was normal compared with Sham.
Capillary density was unchanged. Cardiac myocytes isolated from both regions had
reduced basal and maximal oxygen consumption rate, as well as through complex I
and II, but complex IV activity was unchanged. Reduced respiration was not
associated with detectable reduction of mitochondrial density. There was no
significant change in AMPK or glucose transporter expression levels, but glycogen
content was significantly increased in both MIadjacent and MIremote Glycogen
accumulation was predominantly perinuclear; mitochondria in this area were
smaller but only in MIadjacent where also subsarcolemmal mitochondria were
smaller. In conclusion, after MI reduction of mitochondrial respiration and
glycogen accumulation occur in all LV regions suggesting that reduced perfusion
does not lead to additional specific changes and that increased hemodynamic load
is the major driver for changes in mitochondrial function.
PMID- 27614226
TI - Interaction between the muscle metaboreflex and the arterial baroreflex in
control of arterial pressure and skeletal muscle blood flow.
AB - The muscle metaboreflex and arterial baroreflex regulate arterial pressure
through distinct mechanisms. During submaximal exercise muscle metaboreflex
activation (MMA) elicits a pressor response virtually solely by increasing
cardiac output (CO) while baroreceptor unloading increases mean arterial pressure
(MAP) primarily through peripheral vasoconstriction. The interaction between the
two reflexes when activated simultaneously has not been well established. We
activated the muscle metaboreflex in chronically instrumented canines during
dynamic exercise (via graded reductions in hindlimb blood flow; HLBF) followed by
simultaneous baroreceptor unloading (via bilateral carotid occlusion; BCO). We
hypothesized that simultaneous activation of both reflexes would result in an
exacerbated pressor response owing to both an increase in CO and
vasoconstriction. We observed that coactivation of muscle metaboreflex and
arterial baroreflex resulted in additive interaction although the mechanisms for
the pressor response were different. MMA increased MAP via increases in CO, heart
rate (HR), and ventricular contractility whereas baroreflex unloading during MMA
caused further increases in MAP via a large decrease in nonischemic vascular
conductance (NIVC; conductance of all vascular beds except the hindlimb
vasculature), indicating substantial peripheral vasoconstriction. Moreover, there
was significant vasoconstriction within the ischemic muscle itself during
coactivation of the two reflexes but the remaining vasculature vasoconstricted to
a greater extent, thereby redirecting blood flow to the ischemic muscle. We
conclude that baroreceptor unloading during MMA induces preferential peripheral
vasoconstriction to improve blood flow to the ischemic active skeletal muscle.
PMID- 27614229
TI - The JAK2 V617F mutation and thrombocytopenia.
PMID- 27614228
TI - MYH9-related disorder, a probable May-Hegglin anomaly case series: A tertiary
care experience.
AB - OBJECTIVE/BACKGROUND: May-Hegglin anomaly (MHA) is a rare familial bleeding
disorder characterized by a triad of thrombocytopenia, giant platelets, and Dohle
like inclusion bodies within the leukocytes. The clinical spectrum as well as the
pathophysiology of this entity is not well defined. The objective of this work is
to present a series of three cases of MHA diagnosed in our hospital, where the
patients presented with variable bleeding manifestations, thrombocytopenia, and
giant platelets. MATERIALS AND METHODS: We studied three cases of possible MHA.
In addition to the clinical examination, complete hemogram, and peripheral blood
smear examination, these patients were also subjected to coagulation studies.
Although bleeding symptoms varied among these patients, platelet aggregation
tests with various agonists showed a normal response. RESULTS: Consistent
findings of this entity noted in our patients were mild-to-moderate
thrombocytopenia, giant platelets, and Dohle-like inclusions within the
leukocytes. CONCLUSION: A diagnosis of MHA could be made based on a thorough
peripheral blood smear examination, which also helps to avoid a misdiagnosis of
immune thrombocytopenia.
PMID- 27614225
TI - Traumatic brain injury-induced autoregulatory dysfunction and spreading
depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and
therapeutic implications.
AB - Traumatic brain injury (TBI) is a major health problem worldwide. In addition to
its high mortality (35-40%), survivors are left with cognitive, behavioral, and
communicative disabilities. While little can be done to reverse initial primary
brain damage caused by trauma, the secondary injury of cerebral tissue due to
cerebromicrovascular alterations and dysregulation of cerebral blood flow (CBF)
is potentially preventable. This review focuses on functional, cellular, and
molecular changes of autoregulatory function of CBF (with special focus on
cerebrovascular myogenic response) that occur in cerebral circulation after TBI
and explores the links between autoregulatory dysfunction, impaired myogenic
response, microvascular impairment, and the development of secondary brain
damage. We further provide a synthesized translational view of molecular and
cellular mechanisms involved in cortical spreading depolarization-related
neurovascular dysfunction, which could be targeted for the prevention or
amelioration of TBI-induced secondary brain damage.
PMID- 27614230
TI - Polycythemia vera masked due to severe iron deficiency anemia.
AB - Polycythemia vera is one of the chronic myeloproliferative diseases and very few
patients present with its actual clinical manifestations. The most common
findings are increased red cell mass and an increased leukocyte count with
decreased erythropoietin. We present a case where there was a delay in the
diagnosis of polycythemia because of menorrhagia in the past. On admission, the
patient presented with elevated red and white blood cell counts, erythropoietin
was low, and polycythemia was then suspected. A bcr-abl test was performed to
rule out chronic myelogenous leukemia. JAK2 mutation was positive, and the
patient was diagnosed with polycythemia vera.
PMID- 27614231
TI - Yield of computed tomography pulmonary angiogram in the emergency department in
cancer patients suspected to have pulmonary embolism.
AB - OBJECTIVE/BACKGROUND: The use of computed tomography pulmonary angiography (CTPA)
in the emergency department (ED) for patients suspected to have pulmonary
embolism (PE) has been steadily rising in the last 2decades. However, there are
limited studies that specifically address the use of CTPA in the ED for cancer
patients suspected to have PE. The objective of this study is to assess the rate
of positive PE by CTPA in the ED in cancer patients and the variables that are
associated with positive results. METHODS: A retrospective review of electronic
medical records for 208 consecutive patients with cancer who presented to the ED
and received a CTPA for suspected PE over a 12-month period. The review included
demographics, type and status of cancer, presenting symptoms, CTPA results,
calculation of Wells Score, management based on CT findings, and outcome of
patients. RESULTS: Among the 208 patients who met the inclusion criteria during
our study period (mean age 57+/-13.37years, 73% women, 59% African American, and
32% Caucasians), 5.7% were diagnosed with PE. One hundred and eighty-two (83.7%)
had a Wells Score ?4, of which 2.2% were found to have to have PE, 22 (16.3%)
patients had a Wells Score >4, of which 36.4% were found to have PE (p<.0001).
Sensitivity and specificity of Wells >4 was 66.7% and 92.9%, respectively, with
an odds ratio of 27 (95% CI 6.6-113.6). Receiver operator characteristics area
under the curve for Wells Score was 0.868. Age, race, sex, malignancy type,
stage, status, clinical presentation, D-dimer, and a previous history of venous
thromboembolism were not found to have statistically significant predictive
values. CONCLUSION: The yield of CTPA to rule out PE in patients with cancer
presenting in the ED is low. Following a validated decision-making protocol such
as Wells Criteria may significantly decrease the number of CTPA used in the ED.
PMID- 27614232
TI - Acute promyelocytic leukemia with increased bone marrow reticulin fibrosis:
Description of three cases and review of the literature.
AB - Pathologic increase in bone marrow reticulin fibrosis can be present in many
malignant hematopoietic diseases. In acute leukemia, one-third of patients have
some degree of marrow reticulin fibrosis at presentation, which is thought to be
related to cytokine release from blasts. Marrow fibrosis is particularly common
in acute megakaryoblastic leukemia, while this change is rarely seen in acute
promyelocytic leukemia. Six case reports of acute promyelocytic leukemia with
marrow reticulin fibrosis have been described so far in the literature. Herein,
we present three cases of classical acute promyelocytic leukemia with increased
marrow reticulin fibrosis encountered in our institution, summarizing their
clinicopathologic features, treatment, and outcome to date. Awareness of the
features of acute promyelocytic leukemia with marrow reticulin fibrosis is
important as it may guide treatment options.
PMID- 27614234
TI - Role of Host-Driven Mutagenesis in Determining Genome Evolution of Sigma Virus
(DMelSV; Rhabdoviridae) in Drosophila melanogaster.
AB - Sigma virus (DMelSV) is ubiquitous in natural populations of Drosophila
melanogaster. Host-mediated, selective RNA editing of adenosines to inosines
(ADAR) may contribute to control of viral infection by preventing transcripts
from being transported into the cytoplasm or being translated accurately; or by
increasing the viral genomic mutation rate. Previous PCR-based studies showed
that ADAR mutations occur in DMelSV at low frequency. Here we use SOLiDTM deep
sequencing of flies from a single host population from Athens, GA, USA to
comprehensively evaluate patterns of sequence variation in DMelSV with respect to
ADAR. GA dinucleotides, which are weak targets of ADAR, are strongly
overrepresented in the positive strand of the virus, consistent with selection to
generate ADAR resistance on this complement of the transient, double-stranded RNA
intermediate in replication and transcription. Potential ADAR sites in a
worldwide sample of viruses are more likely to be "resistant" if the sites do not
vary among samples. Either variable sites are less constrained and hence are
subject to weaker selection than conserved sites, or the variation is driven by
ADAR. We also find evidence of mutations segregating within hosts, hereafter
referred to as hypervariable sites. Some of these sites were variable only in one
or two flies (i.e., rare); others were shared by four or even all five of the
flies (i.e., common). Rare and common hypervariable sites were indistinguishable
with respect to susceptibility to ADAR; however, polymorphism in rare sites were
more likely to be consistent with the action of ADAR than in common ones, again
suggesting that ADAR is deleterious to the virus. Thus, in DMelSV, host
mutagenesis is constraining viral evolution both within and between hosts.
PMID- 27614233
TI - Substitutions in the Glycogenin-1 Gene Are Associated with the Evolution of
Endothermy in Sharks and Tunas.
AB - Despite 400-450 million years of independent evolution, a strong phenotypic
convergence has occurred between two groups of fish: tunas and lamnid sharks.
This convergence is characterized by centralization of red muscle, a distinctive
swimming style (stiffened body powered through tail movements) and elevated body
temperature (endothermy). Furthermore, both groups demonstrate elevated white
muscle metabolic capacities. All these traits are unusual in fish and more likely
evolved to support their fast-swimming, pelagic, predatory behavior. Here, we
tested the hypothesis that their convergent evolution was driven by selection on
a set of metabolic genes. We sequenced white muscle transcriptomes of six tuna,
one mackerel, and three shark species, and supplemented this data set with
previously published RNA-seq data. Using 26 species in total (including 7,032
tuna genes plus 1,719 shark genes), we constructed phylogenetic trees and carried
out maximum-likelihood analyses of gene selection. We inferred several genes
relating to metabolism to be under selection. We also found that the same one
gene, glycogenin-1, evolved under positive selection independently in tunas and
lamnid sharks, providing evidence of convergent selective pressures at gene level
possibly underlying shared physiology.
PMID- 27614235
TI - Reference Transcriptomes and Detection of Duplicated Copies in Hexaploid and
Allododecaploid Spartina Species (Poaceae).
AB - In this study, we report the assembly and annotation of five reference
transcriptomes for the European hexaploid Spartina species (S. maritima, S.
alterniflora and their homoploid hybrids S. x townsendii and S. x neyrautii) and
the allododecaploid invasive species S. anglica These transcriptomes were
constructed from various leaf and root cDNA libraries that were sequenced using
both Roche-454 and Illumina technologies. Considering the high ploidy levels of
the Spartina genomes under study, and considering the absence of diploid
reference genome and the need of an appropriate analytical strategy, we developed
generic bioinformatics tools to (1) detect different haplotypes of each gene
within each species and (2) assign a parental origin to haplotypes detected in
the hexaploid hybrids and the neo-allopolyploid. The approach described here
allows the detection of putative homeologs from sets of short reads. Synonymous
substitution rate (KS) comparisons between haplotypes from the hexaploid species
revealed the presence of one KS peak (likely resulting from the tetraploid
duplication event). The procedure developed in this study can be applied for
future differential gene expression or genomics experiments to study the fate of
duplicated genes in the invasive allododecaploid S. anglica.
PMID- 27614236
TI - Morroniside promotes angiogenesis and further improves microvascular circulation
after focal cerebral ischemia/reperfusion.
AB - Preservation of cerebral microvascular functional integrity is crucial for
protecting and repairing the brain after stroke. Our previous study demonstrated
that morroniside promoted angiogenesis 7days after stroke. The current study
aimed to further evaluate the long-term effects of morroniside on angiogenesis
and to examine whether angiogenesis induced by morroniside could improve blood
flow velocity. Sprague-Dawley rats were subjected to middle cerebral artery
occlusion (MCAO), and morroniside was then administered once per day at a dose of
270mg/kg. New vessel formation and the expression of ephrinB2/VEGFR2 signaling
pathway components were examined 14days after MCAO to examine angiogenesis and
the associated mechanisms. The dynamics of regional cerebral blood flow (rCBF)
and the number of vessels of the leptomeningeal anastomoses were analyzed to
characterize microvascular circulation 3days after MCAO. We demonstrated that
morroniside promoted angiogenesis by regulating the ephrinB2/VEGFR2 signaling
pathway 14days post-ischemia. By 3days post-ischemia, morroniside improved rCBF
and increased the number of vessels of the leptomeningeal anastomoses. Moreover,
morroniside decreased the infarct volume and improved neurological function
14days after MCAO. Our findings suggest that morroniside promoted long-term
angiogenesis, thereby improving microvascular circulation and neurological
function. It suggested that the angiogenic mechanism of morroniside might be
mediated by the ephrinB2/VEGFR2 signaling pathway.
PMID- 27614238
TI - Towards chemical profiling of ignitable liquids with comprehensive two
dimensional gas chromatography: Exploring forensic application to neat white
spirits.
AB - The application of GC*GC-FID and GC*GC-MS for the chemical analysis and profiling
of neat white spirit is explored and the benefit of the enhanced peak capacity
offered by comprehensive two-dimensional gas chromatography is demonstrated. An
extensive sampling exercise was conducted throughout The Netherlands and the
production and logistics in terms of bottling and distribution of white spirits
were studied. An exploratory approach based on target-peak tables and principal
component analysis was employed to study the brand-to-brand differences and
production variations over time. Despite the complex chemical composition of
white spirit samples this study shows that chemical variation during productions
is actually quite limited. Hence care has to be taken with the chemical
comparison for forensic purposes. Although some clustering was noticed on brand
level, the large scale production process leads to a very consistent composition
across stores and brands. However, because of the broad specifications of this
commodity product, substantial chemical variation was found over time. This
temporal discrimination could be of forensic value when considering white spirits
supplies in individual households.
PMID- 27614237
TI - Multifunctional organically modified silica nanoparticles for chemotherapy,
adjuvant hyperthermia and near infrared imaging.
AB - We report a novel system of organically modified silica nanoparticles (Ormosil)
capable of near infrared fluorescence and chemotherapy with adjuvant hyperthermia
for image guided cancer therapy. Ormosil nanoparticles were loaded with a
chemotherapeutic, Doxorubicin (DOX) and cyanine dye, IR820. Ormosil particles had
a mean diameter of 51.2+/-2.4 nanometers and surface charge of -40.5+/-0.8mV. DOX
was loaded onto Ormosil particles via physical adsorption (FDSIR820) or covalent
linkage (CDSIR820) to the silanol groups on the Ormosil surface. Both
formulations retained DOX and IR820 over a period of 2 days in aqueous buffer,
though CDSIR820 retained more DOX (93.2%) compared to FDSIR820 (77.0%)
nanoparticles. Exposure to near infrared laser triggered DOX release from
CDSIR820. Uptake of nanoparticles was determined by deconvolution microscopy in
ovarian carcinoma cells (Skov-3). CDSIR820 localized in the cell lysosomes
whereas cells incubated with FDSIR820 showed DOX fluorescence from the nucleus
indicating leakage of DOX from the nanoparticle matrix. FDSIR820 nanoparticles
showed severe toxicity in Skov-3 cells whereas CDSIR820 particles had the same
cytotoxicity profile as bare (No DOX and IR820) Ormosil particles. Furthermore,
exposure of CDSIR820 nanoparticles to Near Infrared laser at 808 nanometers
resulted in generation of heat (to 43 degrees C from 37 degrees C) and resulted
in enhanced cell killing compared to Free DOX treatment. Bio-distribution studies
showed that CDSIR820 nanoparticles were primarily present in the organs of
Reticuloendothelial (RES) system.
PMID- 27614239
TI - Relative studies between hair index, hair area, and medullary index with age and
sex in Thai scalp hair.
AB - Human scalp hair is one of the most common trace materials found at violent crime
scenes. Accordingly, scalp hair is critical evidential material in forensic
investigations for identifying relations and persons, which could result in
solving cases. Knowledge about micro-morphological variations of scalp hair in
the Thai population, however, is scarce, and information on age changes and sex
differences with respect to these traits is limited. The present study was thus
undertaken to explore three micro-morphological parameters of Thai scalp hair
hair index (HI), hair area (HA), medullary index (MI)-relative to age and sex
differences. Scalp hair samples were collected from 340 unrelated Thai cadavers
(170 male, 170 female) of all ages, which were divided into seventeen age groups,
5-year-old interval per group beginning with 0-5years and ending up with >=80
years. Approximately 30 hair strands at the posterior vertex region of the scalp
were cut with scissors as close to the scalp as possible. The hair samples were
subsequently used to make permanent slides, and the mounted hairs were examined
for microscopic cross-sectional characteristics. The authors found that the HI
and MI were similar in the male and female cadavers and did not significantly
differ (p>0.05) according to age. In contrast, the HA was significantly different
between the male and female cadavers at 50-69years of age (p<0.05). There were
other differences according to age as well. That is, the HA increased abruptly
during their early twenties and then decreased gradually until >=80 years of age.
Thus, Thai scalp hair shows some age and sex variations that are reflected in the
HA and might be useful for forensic, medical, and anthropological investigations.
PMID- 27614240
TI - Transradial and transfemoral percutaneous closure of iatrogenic perimembranous
Ventricular Septal Defects using the Amplatzer AVP IV device.
PMID- 27614241
TI - Prolyl hydroxylase domain proteins regulate bone mass through their expression in
osteoblasts.
AB - The roles of prolyl hydroxylase domain proteins (PHDs) in bone are incompletely
understood. Here we deleted the expression of genes encoding PHD1, PHD2, and PHD3
in osteoblasts in mice by breeding the floxed Phd1-3 mice with Col1a1-Cre
transgenic mice. Results showed that mice lacking PHD1-3 in osteoblasts (Phd1-3ob
/-) had increased bone mass. Bone parameters such as bone volume/tissue volume
(BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were
increased, while trabecular spacing (Tb.Sp) was decreased in Phd1-3ob-/- relative
to wild-type (WT) femurs. In contrast, loss of PHD1-3 in osteoblasts did not
alter cortical thickness (Cort.Th). The mineralization apposition rate (MAR) was
increased in Phd1-3ob-/- bone compared to that of wild-type (WT) bone,
demonstrating an enhancement of osteoblast function. Loss of PHD1-3 increased the
number of osteoblast progenitors (CFU-OBs) in bone marrow cultures.
Interestingly, deleting Phd1-3 genes in osteoblasts increased osteoclast
formation in vitro and in bone.
PMID- 27614242
TI - Bifunctional fluorescent benzimidazo[1,2-alpha]quinolines for Candida spp.
biofilm detection and biocidal activity.
AB - Biofilms provide an ideal environment for protecting the microbial cells from
damage caused by humoral and cellular immune system components, promoting
resistance, infections and increasing mortality and morbidity of patients in
health facilities. In an attempt to provide an innovative solution for preventing
contamination in hospital environments, this study evaluated nine structural
complementary fluorescent benzimidazo[1,2-alpha]quinolines as bifunctional agents
that both detect and have biocidal activity against yeast biofilms on stainless
steel surfaces. The benzimidazoles' staining capability was determined by a
fluorescence microscopy study and spraying the substance on yeast biofilm
contaminated stainless steel surfaces. Furthermore, their in vitro human
leukocyte cytotoxicity was evaluated with trypan blue and their biocidal activity
was determined as the minimum inhibitory concentration against Candida
tropicalis, C. albicans and C. parapsilosis strains. Moreover, scanning electron
micrographs were recorded to study the biocidal activity. This resulted in the
identification of 7, which presents all the desired characteristics (such as
solubility) and capabilities (staining and biocide activity against all tested
biofilm forming yeast strains) at the same time. As such, benzimidazole 7 has the
potential to guarantee the use of disinfected medical and surgical instruments in
clinical and surgical procedures, consequently, contributing to an increased
safety for patients.
PMID- 27614243
TI - Extremely high UV-C radiation resistant microorganisms from desert environments
with different manganese concentrations.
AB - Desiccation resistance and a high intracellular Mn/Fe ratio contribute to
ionizing radiation resistance of Deinococcus radiodurans. We hypothesized that
this was a general phenomenon and thus developed a strategy to search for highly
radiation-resistant organisms based on their natural environment. While
desiccation is a typical feature of deserts, the correlation between radiation
resistance and the intracellular Mn/Fe ratio of indigenous microorganisms or the
Mn/Fe ratio of the environment, has not yet been described. UV-C radiation is
highly damaging to biomolecules including DNA. It was used in this study as a
selective tool because of its relevance to early life on earth, high altitude
aerobiology and the search for life beyond Earth. Surface soil samples were
collected from the Sonoran Desert, Arizona (USA), from the Atacama Desert in
Chile and from a manganese mine in northern Argentina. Microbial isolates were
selected after exposure to UV-C irradiation and growth. The isolates comprised 28
genera grouped within six phyla, which we ranked according to their resistance to
UV-C irradiation. Survival curves were performed for the most resistant isolates
and correlated with their intracellular Mn/Fe ratio, which was determined by ICP
MS. Five percent of the isolates were highly resistant, including one more
resistant than D. radiodurans, a bacterium generally considered the most
radiation-resistant organism, thus used as a model for radiation resistance
studies. No correlation was observed between the occurrence of resistant
microorganisms and the Mn/Fe ratio in the soil samples. However, all resistant
isolates showed an intracellular Mn/Fe ratio much higher than the sensitive
isolates. Our findings could represent a new front in efforts to harness
mechanisms of UV-C radiation resistance from extreme environments.
PMID- 27614244
TI - Fluorescent light mediated a green synthesis of silver nanoparticles using the
protein extract of weaver ant larvae.
AB - Alternative to crude plant extracts, a crude protein extract derived from animal
cells is one of the potential sources of biomolecules for mediating a reduction
of silver ions and a formation of silver nanoparticles (AgNPs) under a mild
condition, which very few works have been reported. This work demonstrated a use
of the protein extract of weaver ant larvae as a bio-facilitator for a simple,
green synthesis of AgNPs under fluorescent light at room temperature. The protein
extract of weaver ant larvae exhibited the reducing and antioxidant activities,
which assisted a formation of AgNPs in the reaction containing only silver
nitrate under light exposure. Transmission electron microscopy images revealed
the dispersed, spherical AgNPs with an average size of 7.87+/-2.54nm. The maximum
surface plasmon resonance (SPR) band of the synthesized AgNPs was at 435nm. The
energy-dispersive X-ray analysis revealed that silver was a major element of the
particles. The identity of AgNPs was confirmed by X-ray diffraction pattern,
selected area electron diffraction and high resolution transmission electron
microscopy analyses, which demonstrated the planes of face centered cubic silver.
The synthesized AgNPs showed antibacterial activity against both Escherichia coli
and Staphylococcus aureus with the minimum bactericidal concentration (MBC)
values equally at 250MUg/ml, suggesting their potential application as an
effective antibacterial agent.
PMID- 27614245
TI - The role of acetoacetate in Amadori product formation of human serum albumin.
AB - Amadori product is an important and stable intermediate, which is produced during
glycation process. It is a marker of hyperglycemia in diabetes mellitus, and its
accumulation in the body contributes to microvascular complication of diabetes
including diabetic nephropathy and retinopathy. In this study, the effect of
acetoacetate on the formation of Amadori products and biophysical properties of
human serum albumin (HSA), after incubation with glucose, was investigated using
various methods. These included circular dichroism (CD), Fourier transform
infrared (FTIR) spectroscopy, and UV-visible and fluorescence spectroscopy. Our
results indicated that the production of Amadori products in HSA incubated with
glucose (GHSA) was increased in the presence of acetoacetate. We also detected
alterations in the secondary and tertiary structure of GHSA, which was increased
in the presence of acetoacetate. These changes were attributed to the formation
of covalent bonds between the carbonyl group of acetoacetate and the nucleophilic
groups (lysine residues) of HSA. Thus, acetoacetate can enhance the production of
Amadori products through formation of covalent bonds with biomaterials.
PMID- 27614246
TI - Ligand based pharmacophoric modelling and docking of bioactive pyrazolium 3
nitrophthalate (P3NP) on Bacillus subtilis, Aspergillus fumigatus and Aspergillus
niger - Computational and Hirshfeld surface analysis.
AB - Biologically active Lewis acid-base compound, pyrazolium 3-nitro phthalate (P3NP)
has been synthesized and crystallized by slow evaporation - solution method at 30
degrees C. Spectral and single crystal X-Ray diffraction (XRD) were used to
characterize the compound. The stability of the P3NP was confirmed by UV-Visible
spectral analysis. P3NP crystallizes in monoclinic P21/C space group with cell
parameters, a=13.009 (3) A, b=12.584 (3) A, c=7.529 (18) A and beta=93.052 (4)(o)
with Z=4. Crystal packing was stabilized by N(+)H?O(-), OH?O and CH?O
intermolecular hydrogen bonds. The nature of anion - cation interactions and
crystal packing from various types of intermolecular contacts and their
importance were explored using the Hirshfeld surface analysis. The structure was
optimized by Density Functional Theory at B3LYP level with 6-311++G(d,p) basis
set and the vibrational frequencies were theoretically calculated. Band gap
between Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular
Orbital (LUMO) and Electrostatic potential (ESP) were calculated. Antimicrobial
activities of P3NP with targets were clinically tested and were found to exhibit
antibacterial activity against gram positive and antifungal activity against
pathogens with Minimum Inhibitory Concentration (MIC). Ligand based pharmacophore
modelling was used to understand the potential of P3NP ligand to bind with
selected target proteins. iGEM Dock was used to predict the modes of interactions
of the ligand with target proteins of the microbes predicted from pharmacophore.
PreADMET predicts no absorption of ligand in Human Intestinal Absorption (HIA).
PMID- 27614247
TI - Myelodysplastic syndrome after breast cancer. The challenge of late complications
in long-term survivors.
PMID- 27614249
TI - Measuring JHH values with a selective constant-time 2D NMR protocol.
AB - Proton-proton scalar couplings play important roles in molecule structure
elucidation. However, measurements of JHH values in complex coupled spin systems
remain challenging. In this study, we develop a selective constant-time (SECT) 2D
NMR protocol with which scalar coupling networks involving chosen protons can be
revealed, and corresponding JHH values can be measured through doublets along the
F1 dimension. All JHH values within a network of n fully coupled protons can be
separately determined with (n-1) SECT experiments. Additionally, the proposed
pulse sequence possesses satisfactory sensitivity and handy implementation.
Therefore, it will interest scientists who intend to address structural analyzes
of molecules with overcrowded spectra, and may greatly facilitate the
applications of scalar-coupling constants in molecule structure studies.
PMID- 27614248
TI - Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic
Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment.
AB - INTRODUCTION: The purpose of this study was to explore the complicated
rearrangement mechanisms underlying cases with atypical and negative anaplastic
lymphoma receptor tyrosine kinase gene (ALK) fluorescence hybridization (FISH)
and positive immunohistochemistry (IHC) results and to stress the importance of
combinational assay of these two methods in current pathological diagnosis.
METHODS: A total of 3128 NSCLCs were screened for ALK fusions through both FISH
analysis and IHC assays with Ventana-D5F3 antibody. Fourteen cases with atypical
and negative FISH results with the current criteria and positive IHC results were
analyzed with targeted next-generation sequencing (NGS). RESULTS: Of the 3128
cases tested, 228 (7.3%) and 214 (6.8%) were ALK positive by IHC and FISH,
respectively. Fourteen cases with negative and atypical FISH results all
demonstrated IHC positivity. Of 2991 cases, eight (0.27%) with negative FISH
results demonstrated echinoderm microtubule associated protein like 4 gene (EML4)
ALK fusions revealed by targeted NGS, and the relative abundance of fusion ranged
from 0.9% to 46.8%. Three of 2991 cases (0.1%) did not exhibit any type of ALK
fusions. In addition, two patients showed an isolated 5' side signal and targeted
NGS revealed two novel ALK partner genes, baculoviral IAP repeat containing 6
gene (BIRC6) and phosphatidylinositol binding clathrin assembly protein gene
(PICALM). One patient showed an isolated and attenuated 3' red signal and
demonstrated a novel translocation partner with CCAAT/enhancer binding protein
zeta gene (CEBPZ). Of all the patients, four received crizotinib treatment and
demonstrated partial responses at the end of follow-up. CONCLUSIONS: Our study
showed that patients with negative and atypical ALK FISH patterns may have
positive results for IHC testing and harbor the translocation partners of EML4 or
other genes. Therefore, additional testing with NGS should be conducted to
explore the molecular mechanisms underlying the complicated gene rearrangement
events.
PMID- 27614251
TI - Distribution of coalescent histories under the coalescent model with gene flow.
AB - We propose a coalescent model for three species that allows gene flow between
both pairs of sister populations. The model is designed for multilocus genomic
sequence alignments, with one sequence sampled from each of the three species,
and is formulated using a Markov chain representation that allows use of matrix
exponentiation to compute analytical expressions for the probability density of
coalescent histories. The coalescent history distribution as well as the gene
tree topology distribution under this coalescent model with gene flow are then
calculated via numerical integration. We analyze the model to compare the
distributions of gene tree topologies and coalescent histories for species trees
with differing effective population sizes and gene flow rates. Our results
suggest conditions under which the species tree and associated parameters are not
identifiable from the gene tree topology distribution when gene flow is present,
but indicate that the coalescent history distribution may identify the species
tree and associated parameters. Thus, the coalescent history distribution can be
used to infer parameters such as the ancestral effective population sizes and the
rates of gene flow in a maximum likelihood (ML) framework. We conduct computer
simulations to evaluate the performance of our method in estimating these
parameters, and we apply our method to an Afrotropical mosquito data set
(Fontaine et al., 2015).
PMID- 27614250
TI - Postoperative pain assessment in hospitalised patients: National survey and
secondary data analysis.
AB - BACKGROUND: Measuring pain is important for the adequate pain management of
postoperative patients. The actual compliance with pain assessment in
postoperative patients after implementation of a national safety program is
unknown. OBJECTIVES: The aim of this study is to examine the compliance with pain
assessment in postoperative patients after implementation of a national safety
program, according to the national quality indicators for pain assessment in
postoperative patients. Furthermore, organisational factors associated with this
compliance were determined. STUDY DESIGN: In this study, two data sources were
used: 1) data from an evaluation study of the Dutch Hospital Patient Safety
Program; and 2) data from a questionnaire survey. METHODS: The compliance with
two different pain process indicators was determined: 1) 3 pain measurements a
day, all three full days after surgery; and 2) >=1 pain measurement a day, all
three full days after surgery. Multilevel logistic regression analysis was used
to investigate the association between organisational factors in hospitals and
compliance with pain process indicators. RESULTS: Data of 3895 patient records
from 16 hospitals was included in this study. In 12% of the postoperative
patients, pain was measured 3 times a day, all three full days after surgery. In
53% of the postoperative patients, pain was measured >=1 time a day, all three
full days after surgery. Compliance was highest in general hospitals compared to
tertiary teaching and academic hospitals, and was statistically significantly
higher at the surgery and surgical oncology department compared to the other
departments. CONCLUSIONS: Low compliance was shown with pain assessment in
postoperative patients, according to the process indicator pain after surgery in
Dutch hospitals. This suggests that the implementation of measuring pain in
hospitals is still insufficient.
PMID- 27614252
TI - Hazard Ratio and Repeat Injury for Dementia in Patients With and Without a
History of Traumatic Brain Injury: A Population-Based Secondary Data Analysis in
Taiwan.
AB - The impact of traumatic brain injury (TBI) on the pathogenic hazard ratio (HR)
for dementia patients is still controversial. Some studies have supported the
association between TBI and dementia, especially for Alzheimer's disease, and our
study determined that the HR of dementia patients with and without a history of
TBI or repeated TBI (RTBI). We determined the HR for dementia patients with a
diagnosis of TBI (n = 12931) and a comparative cohort with age- and gender
matched controls (n = 51724) during 2004-2005, using Taiwan's National Health
Insurance Research Database. The adjusted HR (HR = 3.21) for dementia patients
with TBI showed that they were more likely to develop dementia than the
comparison cohort. The HR for dementia patients with RTBI was increased to 3.62.
The results of this large-scale study suggested that TBI increases dementia risk.
Future studies using animal models and epidemiological databases could elucidate
medical and biological mechanisms linking TBI and the development of dementia.
PMID- 27614253
TI - Bacterial toxins activation of abbreviated urea cycle in porcine cerebral
vascular smooth muscle cells.
AB - Nitric oxide (NO) overproduction via induction of inducible nitric oxide synthase
(iNOS) is implicated in vasodilatory shock in sepsis, leading to septic
encephalopathy and accelerating cerebral ischemic injury. An abbreviated urea
cycle (l-citrulline-l-arginine-NO cycle) has been demonstrated in cerebral
perivascular nitrergic nerves and endothelial cells but not in normal cerebral
vascular smooth muscle cell (CVSMC). This cycle indicates that argininosuccinate
synthase (ASS) catalyzes l-citrulline (l-cit) conversion to form
argininosuccinate (AS), and subsequent AS cleavage by argininosuccinate lyase
(ASL) forms l-arginine (l-arg), the substrate for NO synthesis. The possibility
that ASS enzyme in this cycle was induced in the CVSMC in sepsis was examined.
Blood-vessel myography technique was used for measuring porcine isolated basilar
arterial tone. NO in cultured CVSMC and in condition mediums were estimated by
diaminofluorescein (DAF)-induced fluorescence and Griess reaction, respectively.
Immunohistochemical and immunoblotting analyses were used to examine iNOS and ASS
induction. l-cit and l-arg, which did not relax endothelium-denuded normal
basilar arteries precontracted by U-46619, induced significant vasorelaxation
with increased NO production in these arteries and the CVSMCs following 6-hour
exposure to 20MUg/ml lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Pre
treatment with pyrrolidine dithiocarbamate (PDTC) and salicylate (SAL) (NFkappaB
inhibitors), aminoguanidine (AG, an iNOS inhibitor), and nitro-l-arg (NLA, a non
specific NOS inhibitor) blocked NO synthesis in the CVSMC and attenuated l-cit-
and l-arg-induced relaxation of LPS- and LTA-treated arteries. Furthermore,
immunohistochemical and immunoblotting studies demonstrated that expression of
basal iNOS and ASS in the smooth muscle cell of arterial segments denuded of
endothelium and the cultured CVSMCs was significantly increased following 6-hour
incubation with LPS or LTA. This increased iNOS- and ASS-proteins expression in
both preparations was inhibited by SAL, but was further increased by AG. These
results indicate that LPS and LTA induce the l-cit-l-arg-NO cycle via induction
of iNOS and ASS in the CVSMCs, accounting for massively increased NO-production
and cerebral vasodilation in septic shock. Simultaneous inhibition of both
pathways and NFkappaB-activation may be necessary to efficiently decrease or
normalize NO production in the CVSMCs in this disease condition, and/or
prevention and treatment of cerebral vessel-related brain dysfunctions. Our
results further suggest to avoid using iNOS inhibitors alone which may cause
upregulation of iNOS and ASS resulted from feedback-inhibition of iNOS activity.
Accordingly, combined treatments with specific iNOS-activity inhibitor and
inhibitor for iNOS genomic expression may provide a strategy in optimally
managing brain sepsis and related encephalopathy associated with enhanced iNOS
expression and NO overproduction.
PMID- 27614255
TI - Tug of war: adding and removing histone lysine methylation in Arabidopsis.
AB - Histone lysine methylation plays a fundamental role in the epigenetic regulation
of gene expression in multicellular eukaryotes, including plants. It shapes plant
developmental and growth programs as well as responses to the environment. The
methylation status of certain amino-acids, in particular of the histone 3 (H3)
lysine tails, is dynamically controlled by opposite acting histone
methyltransferase 'writers' and histone demethylase 'erasers'. The methylation
status is interpreted by a third set of proteins, the histone modification
'readers', which specifically bind to a methylated amino-acid on the H3 tail.
Histone methylation writers, readers, and erasers themselves are regulated by
intrinsic or extrinsic stimuli; this forms a feedback loop that contributes to
development and environmental adaptation in Arabidopsis and other plants. Recent
studies have expanded our knowledge regarding the biological roles and dynamic
regulation of histone methylation. In this review, we will discuss recent
advances in understanding the regulation and roles of histone methylation in
plants and animals.
PMID- 27614256
TI - Development and validation of a sensitive UHPLC-MS/MS method for quantitation of
prucalopride in rat plasma and its application to pharmacokinetics study.
AB - A rapid, sensitive, selective and accurate ultra high performance liquid
chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed
and validated for the quantitation of prucalopride in rat plasma using
carbamazepine as an internal standard (IS). Separation was achieved on a Waters
ACQUITY UHPLC((r)) HSS C18 column (2.1mm*50mm, 1.8MUm) column with a gradient
mobile phase consisting of acetonitrile-water (containing 0.1% formic acid) as
mobile phase at a flow rate of 0.2mL/min. Prucalopride and IS were monitored
using positive electrospray triple quadrupole mass spectrometer (Waters Xevo TQD)
via multiple reaction monitoring (MRM) mode. The monitored transitions were set
at m/z 367.99->195.89 and m/z 236.97->194.04 for prucalopride and IS,
respectively. The achieved lower limit of quantitation was 0.1ng/mL. The
validated method had an excellent linearity in the range of 0.1-100ng/mL
(r>0.996). The intra- and inter-day precisions were both<=7.8% for prucalopride
and IS, and the average intra- and inter-day accuracies ranged from -3.0% to
8.5%. Extraction recoveries at three levels QC concentrations were in the range
of 90.0-110.0% for prucalopride and 99.6% for IS. Matrix effects were found to be
acceptable. The validated assay was successfully applied to a pharmacokinetic
study of prucalopride following oral administration of 0.25, 0.5, 1.0mg/kg to
female and male rats respectively.
PMID- 27614254
TI - Dietary n-3 PUFAs augment caspase 8 activation in Staphylococcal aureus
enterotoxin B stimulated T-cells.
AB - Epidemiological studies have linked consumption of n-3 PUFAs with a variety of
beneficial health benefits, particularly with respect to putative anti
inflammatory effects. Unfortunately, many of these results remain somewhat
controversial because in most instances there has not been a linkage to specific
molecular mechanisms. For instance, dietary exposure to low levels of mercury has
been shown to be damaging to neural development, but concomitant ingestion of n-3
PUFAs as occurs during consumption of fish, has been shown to counteract the
detrimental effects. As the mechanisms mediating the neurotoxicity of
environmental mercury are not fully delineated, it is difficult to conceptualize
a testable molecular mechanism explaining how n-3 PUFAs negate its neurotoxic
effects. However, environmental exposure to mercury also has been linked to
increased autoimmunity. By way of a molecular understanding of this immuno-toxic
association, disruption of CD95 signaling is well established as a triggering
factor for autoimmunity, and we have previously shown that environmentally
relevant in vitro and dietary exposures to mercury interfere with CD95 signaling.
In particular we have shown that activation of caspase 8, as well as downstream
activation of caspase 3, in response to CD95 agonist stimulation is depressed by
mercury. More recently we have shown in vitro that the n-3 PUFA docosahexaenoic
acid counteracts the negative effect of mercury on CD95 signaling by restoring
caspase activity. We hypothesized that concomitant ingestion of n-3 PUFAs with
mercury might be protective from the immuno-toxic effects of mercury, as it is
with mercury's neuro-toxic effects, and in the case of immuno-toxicity this would
be related to restoration of CD95 signal strength. We now show that dietary
ingestion of n-3 PUFAs generally promotes CD95 signaling by upregulating caspase
8 activation. Apart from accounting for the ability of n-3 PUFAs to specifically
counteract autoimmune sequelae of mercury exposure, this novel finding for the
first time suggests a testable molecular mechanism explaining the overall anti
inflammatory properties of n-3 PUFAs.
PMID- 27614257
TI - Extraction of polyphenols in Himanthalia elongata and determination by high
performance liquid chromatography with diode array detector prior to its
potential use against oxidative stress.
AB - Several studies have demonstrated the antioxidant capacity of seaweeds, which can
be used for the development of biopharmaceuticals with extensive medical
application. Antioxidant therapies appear to attenuate the organic deterioration
originated by an excessive oxidative stress, which could prevent the harmful
effects of various injuries such as ischemia-reperfusion (I/R) among others.
Marine brown seaweeds play a significant role, as they are the only organisms on
earth producing phlorotannins, which are polyphenols that exhibit important
biological activity. To ensure obtaining an extract with the greatest antioxidant
activity, some variables that affect the extraction of polyphenols are optimized,
including seaweed amount, type of solvent, and time and temperature of
extraction. Subsequently, the total phenolic content (TPC) and the antioxidant
activity have been determined. The optimized condition was obtained for 6g of
seaweed, ethanol: water proportion of 60:40 and 2h/60 degrees C, achieving
548.33mg AG/100g seaweed and 76% of antioxidant activity. The characterization of
the extracted polyphenols was made by HPLC/DAD. 11 polyphenols were identified in
the extract: Phloroglucinol, Gallic Acid, Catechin, Rutin, Gentisic Acid,
Chlorogenic Acid, Caffeic Acid, Coumaric, Ferulic, Myricetin and Quercetin.
PMID- 27614259
TI - Bohr effect of avian hemoglobins: Quantitative analyses based on the Wyman
equation.
AB - The Bohr effect data for bar-headed goose, greylag goose and pheasant hemoglobins
can be fitted with the Wyman equation for the Bohr effect, but under one proviso:
that the pKa of His146beta does not change following the T->R quaternary
transition. This assumption is based on the x-ray structure of bar-headed goose
hemoglobin, which shows that the salt-bridge formed between His146beta and
Asp94beta in human deoxyhemoglobin is not formed in goose deoxyhemoglobin. When
the Bohr data for chicken hemoglobin were fitted by making the same assumption,
the pKa of the NH3+ terminal group of Val1alpha decreased from 7.76 to 6.48
following the T->R transition. When the data were fitted without making any
assumption, the pKa of the NH3+ terminal group increased from 7.57 to 7.77
following the T->R transition. We demonstrate that avian hemoglobin Bohr data are
readily fitted with the Wyman equation because avian hemoglobins lack His77beta.
From curve-fitting to Bohr data we estimate the pKas of the NH3+ terminal group
of Val1alpha in the R and T states to be 6.33+/-0.1 and 7.22+/-0.1, respectively.
We provide evidence indicating that these pKas are more accurate than estimates
from kinetic studies.
PMID- 27614258
TI - Applying mini-bore HPAEC-MS/MS for the characterization and quantification of Fc
N-glycans from heterogeneously glycosylated IgGs.
AB - High-performance anion-exchange chromatography (HPAEC) coupled to pulsed
amperometric detection (PAD) is a highly sensitive method for the analysis of
oligosaccharides without the need for prior derivatization. However, the method
suffers from the lack of chemical information with peak assignments based on the
retention times of authentic standards or known peaks of reference materials.
Here we applied HPAEC coupled on-line with electrospray ion trap mass
spectrometry (HPAEC-MS) using a prototype mini-bore (1mm I.D.) CarboPac PA200
column and challenged the analytical separation based method for the structural
assignment of heterogeneous mixtures of N-glycans derived from immunoglobulin G
from human plasma, glyco-engineered CHO cells, and Sp2/0 mouse myeloma cells.
Compared to an analytical scale 3mm I.D. column, the mini-bore column
demonstrated a superior performance with up to 8-fold improved limit of detection
for specific N-glycans determined by PAD. Quantitative evaluation by extracted
ion current chromatograms revealed detection limits in the 50-100 femtomole range
using ion trap MS operated in positive ionization mode. In our hands HPAEC-MS/MS
allowed the detection and quantification of even low abundant glycan species
including biantennary complex-type, high mannose, hybrid and hybrid bisected
structures. In comparison to the detection of N-glycans as lithiated or sodiated
adducts, we obtained a 65-fold improved signal-to-noise ratio with protonated
ions only. Relative quantitative evaluation by single ion current chromatograms
was successfully applied and demonstrated an excellent performance with respect
to selectivity in the relative quantification of heterogeneous samples of N
glycans compared to HPAEC-PAD and HILIC-UPLC of 2-AB labelled N-glycans.
PMID- 27614260
TI - Lower rates of consistent urine drug tests for prescribed psychotropic
medications among patients on opioid replacement therapy.
AB - BACKGROUND: Patients on opioid replacement therapy (ORT) to treat opioid use
disorder are frequently monitored for these medications, but it is not known if
they are also adhering to their psychotropic medications. This is an analysis of
measure of potential adherence to psychotropic medications by patients on ORT.
METHODS: This is a retrospective cohort study of patients (n=1470) on
antidepressants and/or antipsychotics and tested by the Millennium Health
laboratory. Potential adherence to psychotropic medications was measured by urine
drug test (UDT) results. The consistency of UDT for expected psychotropic
medication in patients on ORT was compared to patients not on ORT (control group)
during 3-months period. The study used propensity score methods to match
individuals from both groups on their demographics and their psychotropic
medication. RESULTS: There were 457 participants (31.09%) on ORT and 1013
participants (68.91%) in the control group. Only 55.33% of UDTs (n=1388) were
consistent for expected psychotropic medications in the ORT group compared to
73.69% of UDTs (n=4953) consistent for expected psychotropic medications in the
control group (chi2=172.99, p<0.001). After matching, patients in the ORT group
were less likely than the control group to have consistent UDTs for expected
psychotropic medications (OR: 0.81, 95% CI: 0.76-0.85, P<0.001). CONCLUSION:
There is a high rate of inconsistent UDT for prescribed psychotropic medication
among patients on ORT. This could reflect potential poor adherence. Monitoring
adherence to psychotropic medications should be part of every clinical visit for
patients on ORT.
PMID- 27614261
TI - Leachability, availability and bioaccessibility of Cu and Cd in a contaminated
soil treated with apatite, lime and charcoal: A five-year field experiment.
AB - This study evaluated the efficiency of apatite, lime and charcoal in regulating
Cu and Cd leachability (toxicity characteristic leaching and synthetic
precipitation leaching procedures), availability (CaCl2 and MgCl2) and
bioaccessibility (simplified bioaccessibility extraction test) in a heavy metal
contaminated soil. Both soil pH and soil organic carbon content were investigated
during the five-year field study. The results showed that soil pH and soil
organic carbon content increased with application of amendments, but decreased
with time in both the control and amended plots. Moreover, the leachability,
availability and bioaccessibility of Cu and Cd in amended soils all significantly
decreased compared with the control, but increased over time. Pearson's
correlation analysis showed that soil pH was significantly negatively correlated
with the concentrations of available, leachable and bioaccessible Cu and Cd.
Bioaccessible Cu and Cd were positively correlated with the concentrations of
available and leachable Cu and Cd, but they were not significantly correlated
with soil total Cu and total Cd. Stepwise multiple regression analysis indicated
that the variability in bioaccessible Cu and Cd was well explained by MgCl2
extractable Cu, CaCl2-extractable Cd and pH, respectively. Although the longevity
of amendments decreased with time, apatite was the most effective in decreasing
the availability of Cu, compared with lime and charcoal. These findings provide
valuable insights for risk management during long-term in situ immobilization of
heavy metals in contaminated soils.
PMID- 27614262
TI - Rhamnolipid mediated enhanced degradation of chlorpyrifos by bacterial consortium
in soil-water system.
AB - The study was conducted with the aim to develop an environmentally compatible bio
based system which may rapidly detoxify soil and water polluted by inordinate use
of organophosphate (OP) pesticides. Chlorpyrifos was used as model pesticide as
it degrade slowly due to its low aqueous phase solubility (2ppm) and formation of
antibacterial intermediate 3,5,6, trichloropyridinol (TCP). Five potential
bacteria used in this study belonging to genus Pseudomonas, Klebsiella,
Stenotrophomonas, Ochrobactrum and Bacillus and their mixed culture system
efficiently degraded chlorpyrifos and its toxic intermediates TCP and
diethylthiophosphate (DETP) in aqueous medium. However, degradation rate in soil
water based slurry system was slow as it took 10 days to degrade 82% of added
chlorpyrifos (50mg/kg) by a potential mixed culture CS2 comprised of isolates F-3
and CH-y. This might be due to strong sorption affinity of chlorpyrifos to soil
components which limits its bioavailability. Hence, a crude rhamnolipid
biosurfactant produced by ChlD was used which improved the aqueous phase
solubility of chlorpyrifos by 2-15 folds. This supported CS2 to attain 30% higher
degradation within short period of 6 days as compared to biotic control without
surfactant. Thus, this combination of mixed bacterial population with
biosurfactant significantly improved the rate of chlorpyrifos degradation in soil
without accumulation of toxic intermediates. This environmentally benign
biosurfactant may be produced "in situ" and can replace commonly used toxic
synthetic surfactants for bioremediation purposes.
PMID- 27614263
TI - L-Plastin promotes podosome longevity and supports macrophage motility.
AB - Elucidating the molecular regulation of macrophage migration is essential for
understanding the pathophysiology of multiple human diseases, including host
responses to infection and autoimmune disorders. Macrophage migration is
supported by dynamic rearrangements of the actin cytoskeleton, with formation of
actin-based structures such as podosomes and lamellipodia. Here we provide novel
insights into the function of the actin-bundling protein l-plastin (LPL) in
primary macrophages. We found that podosome stability is disrupted in primary
resident peritoneal macrophages from LPL-/- mice. Live-cell imaging of F-actin
using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that
loss of LPL led to decreased longevity of podosomes, without reducing the number
of podosomes initiated. Additionally, macrophages from LPL-/- mice failed to
elongate in response to chemotactic stimulation. These deficiencies in podosome
stabilization and in macrophage elongation correlated with impaired macrophage
transmigration in culture and decreased monocyte migration into murine
peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived
podosomes and in enabling macrophage motility.
PMID- 27614264
TI - Decreased immunosuppressive actions of 1alpha, 25-dihydroxyvitamin D3 in patients
with immune thrombocytopenia.
AB - Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. 1alpha,
25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D receptor (VDR) play important
immune-suppressive roles in immune system. It has been reported that serum
1,25(OH)2D3 were lower in ITP patients. In this study, we evaluated local
1,25(OH)2D3 level and VDR mRNA expression further, and determined whether
1,25(OH)2D3/VDR were correlated with T cell dysfunction in ITP patients. We found
that 1,25(OH)2D3/VDR levels were decreased in active ITP patients, and
1,25(OH)2D3 had significant anti-inflammatory effects on ITP patients, including
both anti-proliferation of peripheral blood mononuclear cells (PBMCs) and
reversing the abnormal T cells polarization. 1,25(OH)2D3 inhibited the
differentiation of T helper (Th)1 and Tc1 cells but induced the differentiation
of Th2, Tc2 and T regulatory (Treg) cells in ITP patients. However, the
percentage of Th17 cells were not affected obviously with 1,25(OH)2D3. In
addition, 1,25(OH)2D3 also suppressed pro-inflammatory cytokines (INF-gamma and
IL-17A) but promoted anti-inflammatory cytokine (IL-10) secretion in ITP
patients. In conclusion, decreased 1,25(OH)2D3/VDR might participate in the
pathogenesis of ITP, and appropriate supplement of 1,25(OH)2D3 may be a promising
treatment.
PMID- 27614265
TI - Sema4D is required in both the adaptive and innate immune responses of contact
hypersensitivity.
AB - Originally recognized as a regulator of axon guidance in the nervous system,
Semaphorin 4D (Sema4D, CD100) also participates in various immune responses and
many immune-related diseases. However, whether Sema4D is involved in the
pathogenesis of contact hypersensitivity (CHS) remains unclear. In this study, we
explored the role of Sema4D in oxazolone-induced CHS using Sema4D knockout (KO)
mice. We found that Sema4D KO mice developed attenuated CHS responses, as
indicated by milder ear-swelling, lower expression of IL-1beta, IL-6, CXCL2 and
CXCL5, and decreased recruitment of neutrophils, CD8+ T cells and CD4+ T cells.
CHS was impaired in the wide type (WT) mice reconstituted with bone marrow from
Sema4D KO mice, indicating that deletion of Sema4D gene in hematopoietic cells
played a key role in the alleviated CHS in Sema4D KO mice. CHS was also
attenuated in the WT mice transferred with draining lymph nodes (dLNs) cells from
oxazolone-sensitized Sema4D KO mice, and the activation and differentiation of
hapten-specific CD8+ T cells were impaired in Sema4D KO mice. Furthermore, Sema4D
KO mice expressed less IL-1beta and CXCL2 than WT mice after oxazolone
sensitization, and after transferred with dLNs cells from oxazolone-sensitized WT
mice, naive Sema4D KO mice showed attenuated CHS responses upon oxazolone
challenge, indicating that the innate immune response of CHS in Sema4D KO mice
was also abrogated. Taken together, our findings revealed for the first time that
Sema4D positively regulated both the adaptive and innate immune responses in CHS.
PMID- 27614266
TI - Major grass pollen allergens and components detected in a southern Chinese cohort
of patients with allergic rhinitis and/or asthma.
AB - There is so far a paucity of data about allergen component-resolved diagnosis,
and the prevalence of grass pollen allergen components in China, in contrast to
those from western countries. Even in this country, allergies to grass pollen
allergen components in the vast south are inadequately described. This study
aimed to determine the major sensitizing grass pollens in Guangzhou, the largest
city in Guangdong province of southern China. Included in this study were 258
patients having allergic rhinitis with or without asthma and 88 healthy controls.
ImmunoCap100 was used to examine the serum samples for sIgE to Bermuda, Timothy,
and Humulus scandens. Subjects who tested positive were further examined for sIgE
to Bermuda antigen Cyn d 1, Timothy antigens Phl p 1/4/5/6/7/11/12, and CCD. The
relationship of grass pollen allergy to specific antigen sensitization was
assessed. As a result, 22.5% of patients with allergic rhinitis and/or asthma
were positive for Bermuda-sIgE, 13.6% for Timothy-sIgE, and 7.0% for Humulus
scandens-sIgE. These patients were more likely to be sensitized compared with
controls (P<0.001). Of the Bermuda-sIgE positive patients, 53.4% were Cyn d 1
positive and 60.3% were Timothy-sIgE positive. Of the Timothy positive patients,
100% were positive for Phl p 4, 17.1% were positive for Phl p 1 and 8.6% tested
positive for Phl p 5/6/7/11/12. Patients with high Bermuda-sIgE levels were more
likely to be positive for other grasses. In 41.4% of Bermuda grass positive
patients, CCD-sIgE was also positive. Sensitization to Phl p 4 was significantly
correlated with CCD (rs=0.928).In summary, we found that these southern Chinese
patients with allergic rhinitis and/or asthma tested positive for Bermuda,
Timothy, and Humulus scandens IgE. A high Bermuda-sIgE level may predict
sensitization to other grasses. Correlations between sensitization to CCD and
grass pollen allergens suggested a likelihood of cross-reactivity. Further in
vitro inhibition assays are required to confirm this relationship.
PMID- 27614267
TI - Terminating pregnancy for severe hypertension when the fetus is considered non
viable: a retrospective cohort study.
AB - OBJECTIVE: To investigate frequency and practise of termination of pregnancy for
early-onset hypertensive disorders where the fetus is considered to be non
viable. STUDY DESIGN: Retrospective cohort study in all Dutch tertiary perinatal
care centres (n=10), between January 2000 and January 2014. All women who
underwent termination of pregnancy, without fetal surveillance or intention to
intervene for fetal reasons, for early-onset hypertensive disorders in pregnancy,
were analyzed. Women eligible for this study were identified in the local
delivery databases. Medical records were used to collect relevant data. RESULTS:
Between January 2000 and January 2014, 2,456,584 women delivered in The
Netherlands, of which 238,448 (9.7%) in a tertiary care centre. A total of 161
pregnancy terminations (11-12 per year) for severe early-onset preeclampsia were
identified, including 6 women with a twin pregnancy. Mean gestational age at
termination was 172 days (GA 244/7)+/-9.4 days. In 70% of cases termination was
performed at or shortly after 24 weeks' gestation. 74.5% of women developed HELLP
syndrome (n=96), eclampsia (n=10) or needed admission to an ICU (n=14). Birth
weight was below 500g in 64% of cases. In 69% of the cases the estimated fetal
weight was within a 10% margin of the actual birth weight. CONCLUSION:
Termination of pregnancy for early-onset hypertensive disorders without
intervention for fetal indication occurs approximately 12 times per year in The
Netherlands. More data are needed to investigate contemporary best practice
regarding termination of pregnancy for early-onset hypertensive indications at
the limits of fetal viability. Considering the frequency of maternal
complications, termination of pregnancy and not expectant management should be
considered for all women presenting with severe early onset hypertensive
disorders at the limits of fetal viability.
PMID- 27614269
TI - Physician morality and perinatal decisions.
AB - OBJECTIVE: Given the same set of "facts" (e.g. fetal prognosis) different
physicians may not give the same advice to patients. Studies have shown that
people differ in how they prioritize moral domains, but how those domains
influence counseling and management has not been assessed among obstetricians.
Our objective was to see if, given the same set of facts, obstetricians'
counseling would vary depending on their prioritization of moral domains. DESIGN:
Obstetricians completed questionnaires that included validated scales of moral
domains (e.g. autonomy, community, divinity), demographic data, and hypothetical
scenarios (e.g. how aggressively they would pursue the interests of a potentially
compromised child, the degree of deference they gave to parents' choices, and
their relative valuation of fetal rights and women's rights). Multivariate
logistic regression using backwards conditional selection was used to explore how
participants responded to the moral dilemma scenarios. RESULTS: Among the 249
participating obstetricians there was wide variation in counseling, much of which
reflected differences in prioritization of moral domains. For example, requiring
a higher likelihood of neonatal survival before recommending a cesarean section
with cord prolapse was associated with Fairness/Reciprocity, an autonomy domain
which emphasizes treating individuals equally (OR=1.42, 90% CI=1.06-1.89,
p=0.05). Honoring parents' request to wait longer to suspend attempts to
resuscitate an infant with no heart rate or pulse was associated with the
community domains (involving concepts of loyalty and hierarchy) of In
Group/Loyalty; OR 1.30, 90% CI=1.04-1.62, p=0.05 and Authority/Respect (OR=1.34,
90% CI=1.06-1.34, p=0.045). Carrying out an unconsented cesarean section was
associated with In-Group Loyalty (OR=1.26, 90% CI=1.01-1.56, p=0.08) and
religiosity (OR=1.08, 90% CI=1.00-1.16, p=0.08). CONCLUSION: The advice that
patients receive may vary widely depending on the underlying moral values of
obstetricians. Physicians should be aware of their "biases" in order to provide
the most objective counseling possible.
PMID- 27614268
TI - Long-term follow-up and quality of life after robot assisted sacrohysteropexy.
AB - OBJECTIVE: The aim of this study is to investigate the effect of robot assisted
laparoscopic sacrohysteropexy (RALS), with preservation of the uterus, in
patients with pelvic organ prolapse on short and long term outcome. We report on
(anatomical) status of the prolaps and the associated health related quality of
life of women treated with RALS before and five years after surgery. STUDY
DESIGN: A prospective cohort study in a teaching hospital in The Netherlands was
performed. Quality of life was assessed pre-operative, post-operative and five
years after RALS using the UDI/IIQ validated self-questionnaire designed for
Dutch-speaking patients. Clinical and operative data were prospectively collected
up to five years. Statistical analysis of categorical data was performed with the
paired T-test. Descriptive statistics were computed with the use of standard
methods for means, median and proportions. RESULTS: Hundred women with utero
vaginal prolapse were treated with RALS with preservation of the uterus. The
overall success rate of pelvic organ prolapse (POP) was 89.2%. After surgery the
quality of life improved (P<0.05) Overall health status, based on a 0-100% visual
analogue scale (VAS), improved from 72.6% pre-operative to 82.2% six weeks
postoperative (P<0.05). Postoperative patients experienced less feelings of
nervousness (P=0.01), shame (P<0.05) and frustration (P<0.05). The positive
effects on these feelings remained present after five years. The learning curve
shows a decrease in operating time with gained experience. CONCLUSION: RALS has
proven to be a safe and effective treatment for uterine preserving surgery in
cases of pelvic organ prolapse. The long term anatomical outcomes and quality of
life after RALS compare favorably with laparoscopic and open hysteropexy.
PMID- 27614270
TI - Maternal heart rate during the first 48h postpartum: a retrospective cross
sectional study.
AB - OBJECTIVES: 1) Describe the distribution of heart rate in the first 48h
postpartum in women with no evidence of sepsis, anaemia or haemorrhage. 2)
Investigate the relationship between postpartum heart rate and other maternal
factors. STUDY DESIGN: A retrospective cross-sectional study of postpartum women
who delivered between July 2012 and June 2015 in a tertiary hospital. Data was
analysed from the local maternity system and electronic vital signs database. The
main outcome measures: Heart rate at 6, 12, 24 and 48h postpartum. RESULTS: Data
were obtained on 11401 women. After exclusion of women with possible sepsis,
anaemia or haemorrhage, 7627 heart rate readings from 5164 women were analysed.
Mean heart rate (+2SD/+3SD) at 6h was 83.6 (108.2/120.6), 12h 84.5 (109.4/121.9),
24h 85.4 (110.4/122.9), and 48h 84.3 (109.7/122.4). There was statistical
correlation of post partum heart rate with body mass index (BMI), age and
discharge haemoglobin. CONCLUSION: This study describes the distribution of
maternal heart rate in the early postpartum period, in women with no evidence of
sepsis, anaemia or major haemorrhage. This will facilitate identification and
appropriate investigation of women with abnormal heart rates. Although
correlation with BMI, age and discharge haemoglobin was demonstrated, the
differences were small and not clinically meaningful. Further work investigating
the relationship between postpartum heart rate and poor maternal outcomes is
required.
PMID- 27614271
TI - The influence of pore size and stiffness on tenocyte bioactivity and
transcriptomic stability in collagen-GAG scaffolds.
AB - Orthopedic injuries, particularly those involving tendons and ligaments, are some
of the most commonly treated musculoskeletal ailments, but are associated with
high costs and poor outcomes. A significant barrier in the design of biomaterials
for tendon tissue engineering is the rapid de-differentiation observed for
primary tenocytes once removed from the tendon body. Herein, we evaluate the use
of an anisotropic collagen-glycosaminoglycan (CG) scaffold as a tendon
regeneration platform. We report the effects of structural properties of the
scaffold (pore size, collagen fiber crosslinking density) on resultant tenocyte
bioactivity, viability, and gene expression. In doing so we address a standing
hypothesis that scaffold anisotropy and strut flexural rigidity (stiffness) co
regulate long-term maintenance of a tenocyte phenotype. We report changes in
equine tenocyte specific gene expression profiles and bioactivity across a
homologous series of anisotropic collagen scaffolds with defined changes in pore
size and crosslinking density. Anisotropic scaffolds with higher crosslinking
densities and smaller pore sizes were more able to resist cell-mediated
contraction forces, promote increased tenocyte metabolic activity, and maintain
and increase expression of tenogenic gene expression profiles. These results
suggest that control over scaffold strut flexural rigidity via crosslinking and
porosity provides an ideal framework to resolve structure-function maps relating
the influence of scaffold anisotropy, stiffness, and nutrient biotransport on
tenocyte-mediated scaffold remodeling and long-term phenotype maintenance.
PMID- 27614272
TI - A new earthworm cellulase and its possible role in the innate immunity.
AB - A new endogenous cellulase (Ean-EG) from the earthworm, Eisenia andrei and its
expression pattern are demonstrated. Based on a deduced amino acid sequence, the
open reading frame (ORF) of Ean-EG consisted of 1368 bps corresponding to a
polypeptide of 456 amino acid residues in which is contained the conserved region
specific to GHF9 that has the essential amino acid residues for enzyme activity.
In multiple alignments and phylogenetic analysis, the deduced amino acid sequence
of Ean- EG showed the highest sequence similarity (about 79%) to that of an
annelid (Pheretima hilgendorfi) and could be clustered together with other GHF9
cellulases, indicating that Ean-EG could be categorized as a member of the GHF9
to which most animal cellulases belong. The histological expression pattern of
Ean-EG mRNA using in situ hybridization revealed that the most distinct
expression was observed in epithelial cells with positive hybridization signal in
epidermis, chloragogen tissue cells, coelomic cell-aggregate, and even blood
vessel, which could strongly support the fact that at least in the earthworm,
Eisenia andrei, cellulase function must not be limited to digestive process but
be possibly extended to the innate immunity.
PMID- 27614273
TI - Maternal near miss approach to evaluate quality of care in Alborz province, Iran.
AB - OBJECTIVE: the maternal near miss approach has been developed by World Health
Organization for assessing and improving the quality of care. This study aimed to
examine the incidence, characteristics, and features of the care provided for
maternal near-miss cases in public and private hospitals in Alborz province,
Iran. METHODS: a cross sectional, facility-based study was conducted in all 13
public and private hospitals of Alborz province between April 2012 and December
2012. The World Health Organization near miss criteria were applied to gather and
analyse the data, and indicators related to maternal near miss, access to and
quality of maternal care. FINDINGS: 38,715 deliveries were assessed. There were
38,663 live births, 419 (1.08%) had potentially life-threatening conditions and
199 had severe maternal outcomes (SMO) (192 near miss cases and 7 maternal
deaths). The maternal near-miss ratio was 4.97 cases per 1000 live births. The
incidence of severe maternal outcome was 5.15 cases per 1000 live births. Severe
mortality outcomes index within 12 hours of hospital stay from admission (SMO12)
was 3.52%. The proportion of SMO12 cases from the total SMO cases was 99.5%. The
Intensive Care Unit (ICU) admission rate among women with SMO was 72.7%, while
the overall admission rate was 0.7%. Overall, hypertensive disorder was the most
frequent condition among women with potentially life-threatening conditions and
maternal near-miss cases. Cardiovascular dysfunction and respiratory dysfunction
were the most prevalent dysfunctions among maternal near miss (MNM) cases and
maternal death cases respectively. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
the WHO maternal near miss criteria help to identify issues that may lead to life
threatening conditions and can be used to monitor and improve the quality of care
in maternity settings. Hypertensive disorders related to near miss conditions
need more attention to prevent maternal severe outcomes in Alborz province. Most
of the process indicators were not satisfactory. The WHO tool enables health
managers to improve maternal health care.
PMID- 27614274
TI - Working memory studies among individuals with intellectual disability: An
integrative research review.
AB - BACKGROUND: Integrative research review infers generalizations about a
substantive subject, summarizes the accumulated knowledge that research has left
unresolved and generates a new framework on these issues. Due to methodological
issues emerging from working memory (WM) studies in the population with non
specific intellectual disability (NSID) (N=64) between 1990-2014, it is difficult
to conclude on WM performance in this population. AIM: This integrative research
review aimed to resolve literature conflicts on WM performance among individuals
with NSID and to identify the conditions/moderators that govern their WM
performance compared to controls with Typical development. METHOD/PROCEDURE: We
used the six stages of integrative research review: problem formulation, data
collection, evaluation, data analysis, results, interpretation and discussion.
OUTCOMES AND RESULTS: The findings indicate two types of moderators that
determine WM performance in the population with NSID: Participants' moderators
(criteria for matching the ID and TD groups, CA and MA), and task moderators [the
three WM components of Baddeley and Hitch's (1974) model and task load]. Only an
interaction between the two moderators determines WM performance in this
population. The findings indicate a hierarchy (from more to less preserved) in WM
performance of individuals with NSID: The visuospatial tasks, then some of the
executive functions tasks, and the phonological loop tasks being less preserved.
Furthermore, at a low level of control, the performance of participants with NSID
was preserved beyond the modality and vice versa. CONCLUSIONS AND IMPLICATIONS:
Modality and MA/intelligence determine WM performance of individuals with ID.
Educators should prepare intervention programs take the impact of the two
moderators into account.
PMID- 27614275
TI - Scale of emotional development-Short.
AB - BACKGROUND: Intellectual disability (ID) is often accompanied by delays in
emotional development (ED) that may result in challenging behavior. Insight into
emotional functioning is crucial for appropriate diagnostic assessment in adults
with ID. However, few standardized assessment instruments are available. AIMS:
The aim of this study was to develop a short, psychometrically sound instrument
for assessing levels of ED in individuals with ID: The Scale of Emotional
Development - Short (SED-S), which can be applied to adults. METHODS AND
PROCEDURES: The Scale for ED - Revised2 (SED-R2) was taken as a point of
departure. In a first step, the validity and observability of the items (N=556)
in the SED-R2 were assessed by 30 experts from Germany, Belgium, and The
Netherlands. The SED-S was then constituted in a consecutive consensus process,
in which items to be included were selected based on their assessments and
subsequently rephrased, and in which the structure and method of administering
the new scale were agreed upon. OUTCOMES AND RESULTS: The SED-S consists of 200
binary items describing five levels of emotional functioning (reference ages: 0
12 years) within eight domains: Relating to His/Her Own Body, Relating to
Significant Others, Dealing with Change - Object Permanence, Differentiating
Emotions, Relating to Peers, Engaging with the Material World, Communicating with
Others, and Regulating Affect. CONCLUSIONS AND IMPLICATIONS: The SED-S offers an
empirical-based, practical tool to assessing ED in adults with ID. Further
research will be needed to meet the requirements of a standardized diagnostic
instrument.
PMID- 27614276
TI - Benefits of an experimental program of equestrian therapy for children with ADHD.
AB - BACKGROUND: Equestrian therapy has been shown to be a useful instrument in the
sphere of the emotional wellbeing and mental health of different population
groups. AIMS: To empirically determine the effects of a program of equestrian
therapy on quality of life and various psychosocial variables of a group of 14
pupils diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), aged from
7 to 14 years. METHODS AND PROCEDURES: A quasi-experimental design, with a pre
test and a post-test, was implemented with an experimental group and a control
group. The program consisted of 24 biweekly sessions, therefore lasting some 3
months. The data acquisition instruments used were: the "Behavior Assessment
System for Children" (BASC) and an ad-hoc quality of life questionnaire. OUTCOMES
AND RESULTS: The results deriving from the teachers' responses and the different
scales of the BASC showed no significant group differences, but for the
experimental group there was an improvement in the indicator corresponding to
interpersonal relationships in the quality-of-life questionnaire. CONCLUSIONS AND
IMPLICATIONS: It would seem that it is currently possible to recommend this
activity, for this target population, as a sporting activity that provides
similar benefits to other physical activities, but which is still far from being
able to be recognized as a therapeutic activity.
PMID- 27614277
TI - Premature trial discontinuation often not accurately reflected in registries:
comparison of registry records with publications.
AB - BACKGROUND: One quarter of randomized clinical trials (RCTs) are prematurely
discontinued and frequently remain unpublished. Trial registries can document
whether a trial is ongoing, suspended, discontinued, or completed and therefore
represent an important source for trial status information. The accuracy of this
information is unclear. OBJECTIVE: To examine the accuracy of completion status
and reasons for discontinuation documented in trial registries as compared to
corresponding publications of discontinued RCTs and to investigate potential
predictors for accurate trial status information in registries. METHODS: We
conducted a cross-sectional study comparing information provided in publications
(reference standard) to corresponding registry entries. First, we reviewed
publications of RCTs providing information on both discontinuation and
registration. We identified eligible publications through systematic searches of
MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs
initiated between 2000 and 2003. Second, pairs of investigators independently and
in duplicate extracted data from publications and corresponding registry records.
Third, for each discontinued RCT, we compared publication information to registry
information. We used multivariable regression to examine whether accurate
labeling of trials as discontinued (vs. other status) in the registry was
associated with recent initiation of RCT, industry sponsorship, multicenter
design, or larger sample size. RESULTS: We identified 173 publications of RCTs
that were discontinued due to slow recruitment (55%), harm (16%), futility (11%),
benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were
registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries
(8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as
discontinued and 57 (33%) provided a reason for discontinuation (of which 53,
93%, provided the same reason as in the publication). Labeling of discontinued
trials as discontinued (vs. other label) in corresponding trial registry records
improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04
1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but
unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89
1.29). CONCLUSIONS: Less than half of published discontinued RCTs were accurately
labelled as discontinued in corresponding registry records. One-third of registry
records provided a reason for discontinuation. Current trial status information
in registries should be viewed with caution.
PMID- 27614278
TI - Precision Across Scientific Methods: Integrating Rigor and Care Into Assessment
of Nutrition Education and Behavior Outcomes.
PMID- 27614280
TI - Reaching New Audiences Using Electronic Magazines for Microwave Food Safety
Education.
PMID- 27614279
TI - Evaluation of US Veterans Nutrition Education for Diabetes Prevention.
AB - OBJECTIVE: Evaluate the effectiveness of nutrition education interventions for
diabetes prevention. DESIGN: Retrospective cohort design. SETTING: Tertiary-care
US Veterans' Hospital, July 2007 to July 2012, using pre-existing database.
PARTICIPANTS: Prediabetic, adult veterans (n = 372), mostly men (94.4%, n = 351).
INTERVENTIONS: Visits with existing nutrition education classes were collected.
MAIN OUTCOME MEASURES: PRIMARY OUTCOME: diabetes status; predictors:
visits/encounters, age, body mass index, weight change, and hemoglobin A1c.
ANALYSIS: Cox proportional hazards method, chi(2) test, and logistic regression.
RESULTS: In this sample, prediabetic veterans who received nutrition education
were less likely to develop diabetes when compared with prediabetic veterans who
did not receive nutrition education (hazard ratio, 0.71; 95% confidence interval,
0.55-0.92; P < .01). This difference remained significant after adjusting for
body mass index and weight change. CONCLUSIONS AND IMPLICATIONS: Nutrition
education was significantly associated with preventing the progression from
prediabetes to diabetes in US Veterans participating in a nutrition education
intervention at the Michael E. DeBakey Veterans Affairs Medical Center.
PMID- 27614281
TI - Assessing the Nutrition Literacy of Parents and Its Relationship With Child Diet
Quality: Methodological and Statistical Issues.
PMID- 27614282
TI - Response to Letter to the Editor.
PMID- 27614283
TI - Correlation between the virulence of T. cruzi strains, complement regulatory
protein expression levels, and the ability to elicit lytic antibody production.
AB - Trypanosoma cruzi trypomastigotes are able to resist lysis via the complement
system, which involves many surface proteins including the complement regulatory
protein (CRP). To examine the diversity in CRP recognition among strains of T.
cruzi, the expression levels of the translated protein on trypomastigote surfaces
were analyzed by flow cytometry, and associations between protein expression and
the biological behavior of these strains, especially the ability to induce lytic
antibodies in animal models, were assessed. The highly virulent T. cruzi strains
Ninoa, INC-5, and Colombiana and the less virulent strains CL-Brener, LGB-231,
and JG were used in the experiments. An expression profile analysis showed that
the Colombiana and INC-5 strains have higher translated protein levels and
induced higher production of antibodies in mice than the other strains. Our
results indicated that there are differences in the surface expression of CRP
between parasite strains, with a tendency for the most virulent strains to have
higher expression levels. Combined, these results contribute to a better
understanding of CRP functions and the complexity of host-parasite interactions,
considering the large number of virulence factors involved in the process.
PMID- 27614284
TI - Gomesin acts in the immune system and promotes myeloid differentiation and
monocyte/macrophage activation in mouse.
AB - Due to the cytotoxic effect of antimicrobial peptides (AMP) against several
microorganism and tumor cells has been proposed their association with the immune
system. However, just a few reports have shown this relationship. In this study,
mice were treated with gomesin, a beta-hairpin AMP that exhibit high cytotoxicity
against bacterial and tumor cells. Different effects in the immune system were
observed, such as, decrease of CD3+ in T lymphocytes (Control: 17.7+/-1.4%;
Gomesin: 7.67+/-1.2%) and in hematopoietic progenitors and increase of
hematopoietic stem cell (Control: 0.046+/-0.004%; Gomesin: 0.067+/-0.003%), B220+
B lymphocytes (Control: 38.63+/-1.5%; Gomesin: 47.83+/-0.48%), and Mac-1+F4/80+
macrophages (Control: 11.76+/-3.4%; Gomesin: 27.13+/-4.0%). Additionally,
macrophage increase was accompanied by an increase of macrophage phagocytosis
(Control 20.85+/-1.53; Gomesin 31.32+/-1 Geometric mean), interleukin 6 (Control:
47.24+/-1.9ng/mL; Gomesin: 138.68+/-33.68ng/mL) and monocyte chemoattractant
protein-1 (Control: 0.872+/-0.093ng/mL; Gomesin: 1.83+/-0.067ng/mL). Thus, this
report showed immunomodulatory activity of gomesin in the immune system of mice.
PMID- 27614285
TI - Oxidative stress responses in the animal model, Daphnia pulex exposed to a
natural bloom extract versus artificial cyanotoxin mixtures.
AB - In the natural environment, Daphnia spp. are constantly exposed to a complex
matrix of biomolecules, especially during cyanobacterial bloom events. When
cyanobacterial cells decay, not only are toxic secondary metabolites known as
cyanotoxins released, but also multiple other secondary metabolites, some of
which act as enzyme inhibitors. The present study examined the effects of such a
natural toxin matrix (crude extract from a bloom) versus artificial toxin
mixtures in terms of oxidative stress in Daphnia pulex. The results indicate that
there is no significant effect on the survival of D. pulex. However, exposure to
the bloom extract resulted in increased lipid peroxidation over a shorter
exposure period and reduced antioxidative enzyme activities when compared to the
artificial mixtures. The daphnids also needed a longer recovery time to reduce
the increased cellular hydrogen peroxide concentration associated with the
exposure to the crude extract than with the artificial mixtures. The results
indicate a significant difference between the bloom crude extract and the two
synthetic mixtures for all stress markers tested, indicating enhanced toxicity of
the bloom extract.
PMID- 27614286
TI - What follows refractory cardiac arrest: Death, extra-corporeal cardiopulmonary
resuscitation (E-CPR), or uncontrolled donation after circulatory death?
PMID- 27614287
TI - Surgical Repair of an Impalement Genital Injury from an Inline Skating Accident
in a 7-Year-Old Prepubertal Girl: A Case Report.
AB - BACKGROUND: In girls who present with vaginal trauma, sexual abuse is often the
primary diagnosis. The differential diagnosis must include patterns and the
mechanism of injury that differentiate accidental injuries from inflicted trauma.
CASE: A 7-year-old prepubertal girl presented to the emergency department with
genital bleeding after a serious accidental impaling injury from inline skating.
After rapid abduction of the legs and a fall onto the blade of an inline skate
this child incurred an impaling genital injury consistent with an accidental
mechanism. The dramatic genital injuries when repaired healed with almost
imperceptible residual evidence of previous trauma. SUMMARY AND CONCLUSION: To
our knowledge, this case report represents the first in the medical literature of
an impaling vaginal trauma from an inline skate and describes its clinical and
surgical management.
PMID- 27614288
TI - Longstanding Presence of a Vaginal Foreign Body (Battery): Severe Stenosis in a
13-Year-Old Girl.
AB - BACKGROUND: In recurrent/unresponsive vaginal discharge a vaginal foreign body
should be considered. CASE: We present the case of a 13-year-old girl who
suffered from a foul-smelling dark brownish and malodorous vaginal discharge
since the age of 7 years. When the girl was 11 years old, a foreign body was
discovered on ultrasound imaging; removal by colposcopy failed, because of the
complete battery inclusion in the posterior vaginal wall. Two years later, at our
institution, radiological images yielded the general position of the foreign
body; colposcopy showed complete vaginal stenosis. Forced dilatation allowed
surgical removal of the battery which was embedded in the vaginal fundal wall.
SUMMARY AND CONCLUSION: Early removal of foreign objects prevents ulceration,
necrosis, stenosis, perforations, and late serious sequelae such as pelvic
inflammation and infertility.
PMID- 27614290
TI - An event-related potential study of the relationship between N170 lateralization
and phonological awareness in developing readers.
AB - As reading development progresses, the visual processing of word forms becomes
increasingly left-lateralized. This is visible, among other ways, as increased
left-lateralization of the N170 ERP component. A primary explanation of this
effect, the phonological mapping hypothesis, proposes that the left
lateralization of visual word form processing that accompanies reading
development is the result of calling upon left hemisphere auditory language
regions to perform the linking of orthography with phonology (phonological
mapping). A key, but untested, prediction of the phonological mapping hypothesis
is thus that individuals with greater phonological awareness should exhibit more
left lateralized visual processing of word forms than individuals with poorer
phonological awareness. We set out to test this hypothesis here. We accomplished
this by collecting ERPs while children grades 5-6 viewed words, objects, and
word/object ambiguous items (e.g., "SMILE" shaped like a smile - hereafter
referred to as wobjects). Results revealed that, consistent with the phonological
mapping hypothesis, individual phonological awareness (but not other measures of
reading development) predicted left-lateralization of the N170 component elicited
in response to words (but not item types that were not word-like).
PMID- 27614289
TI - Tissue-specific response of carbohydrate-responsive element binding protein
(ChREBP) to mammalian hibernation in 13-lined ground squirrels.
AB - Mammalian hibernation is characterized by a general suppression of energy
expensive processes and a switch to lipid oxidation as the primary fuel source.
Glucose-responsive carbohydrate responsive element binding protein (ChREBP) has
yet to be studied in hibernating organisms, which prepare for the cold winter
months by feeding until they exhibit an obesity-like state that is accompanied by
naturally-induced and completely reversible insulin resistance. Studying ChREBP
expression and activity in the hibernating 13-lined ground squirrel is important
to better understand the molecular mechanisms that regulate energy metabolism
under cellular stress. Immunoblotting was used to determine the relative
expression level and subcellular localization of ChREBP, as well as serine
phosphorylation at 95 kDa, comparing euthermic and late torpid ground squirrel
liver, kidney, heart and muscle. DNA-binding ELISAs and RT-PCR were used to
explore ChREBP transcriptional activity during cold stress. ChREBP activity
seemed generally suppressed in liver and kidney. During torpor, ChREBP total
protein levels decreased to 44% of EC in liver, phosphoserine levels increased
2.1-fold of EC in kidney, and downstream Fasn/Pkl transcript levels decreased to
<60% of EC in liver. By contrast, ChREBP activity generally increased during
torpor in cardiac and skeletal muscle, where ChREBP total protein levels
increased over 1.5-fold and 5-fold of EC in muscle and heart, respectively; where
DNA-binding increased by ~2-fold of EC in muscle; and where Fasn transcript
levels increased over 3-fold and 7-fold in both muscle and heart, respectively.
In summary, ChREBP has a tissue-specific role in regulating energy metabolism
during hibernation.
PMID- 27614291
TI - Distinct progression of the deterioration of thematic and taxonomic links in
natural and manufactured objects in Alzheimer's disease.
AB - Taxonomic and thematic relationships are core elements of lexico-semantic
networks. However, the weight of both links differs in semantic memory, with
distinct support for natural and manufactured objects: natural objects tend to be
more taxonomically identified while manufactured objects benefit more from the
underlying thematic relationships. Alzheimer's disease (AD) causes early semantic
memory impairment characterized by a category-specific deterioration, where
natural objects are more sensitive to the disease than manufactured objects.
However, relatively few studies have examined the progressive deterioration of
specific thematic versus taxonomic relations in both categories of objects in AD.
To better understand semantic memory disorganization in AD and analyze the
potential interaction effect between the category (natural/manufactured), the
condition (thematic/taxonomic) and AD, we will investigate the lexico-semantic
network in 82 AD patients (divided into three groups depending on their global
cognitive deterioration and their performance in a preliminary semantic knowledge
questionnaire (mild (AD1), moderate (AD2) and advanced (AD3) stages of semantic
knowledge alteration). The experimental protocol contains two tasks: an implicit
semantic priming paradigm and an explicit card-sorting test that uses the same
items, equally divided between natural and manufactured objects. Results show a
distinct taxonomic and thematic evolution pattern with early taxonomic
deterioration. Natural objects are also more vulnerable to the disease. Lastly,
there is an interaction effect between the category and the condition in the
priming task indicating that natural objects are more taxonomically organized and
manufactured objects benefit more from both thematic and taxonomic organizations,
reinforcing the idea of the robustness of this category. The theoretical accounts
of these observations will be discussed in detail.
PMID- 27614292
TI - Distribution patterns and impact of transposable elements in genes of green
algae.
AB - Transposable elements (TEs) are DNA sequences able to transpose in the host
genome, a remarkable feature that enables them to influence evolutive
trajectories of species. An investigation about the TE distribution and TE impact
in different gene regions of the green algae species Chlamydomonas reinhardtii
and Volvox carteri was performed. Our results indicate that TEs are very scarce
near introns boundaries, suggesting that insertions in this region are negatively
selected. This contrasts with previous results showing enrichment of tandem
repeats in introns boundaries and suggests that different evolutionary forces are
acting in these different classes of repeats. Despite the relatively low
abundance of TEs in the genome of green algae when compared to mammals, the
proportion of poly(A) sites derived from TEs found in C. reinhardtii was similar
to that described in human and mice. This fact, associated with the enrichment of
TEs in gene 5' and 3' flanks of C. reinhardtii, opens up the possibility that TEs
may have considerably contributed for gene regulatory sequences evolution in this
species. Moreover, it was possible identify several instances of TE exonization
for C. reinhardtii, with a particularly interesting case from a gene coding for
Condensin II, a protein involved in the maintenance of chromosomal structure,
where the addition of a transposomal PHD finger may contribute to binding
specificity of this protein. Taken together, our results suggest that the low
abundance of TEs in green algae genomes is correlated with a strict negative
selection process, combined with the retention of copies that contribute
positively with gene structures.
PMID- 27614293
TI - Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts
embryo nucleolar precursor bodies.
AB - The nucleolus is the site of ribosome biogenesis and forms around the actively
transcribed ribosomal RNA (rRNA) genes. However, the nucleolus is also implicated
in cell cycle regulation, tumour suppression and chromosome segregation and
nucleolar disfunction is linked to a wide range of human diseases. Interestingly,
the nucleolus is also required for genome reprogramming and the establishment of
heterochromatin in the mammalian embryo. Mammalian oocytes contain a subnuclear
structure that is believed to be the precursor of the functional nucleolus, the
Nucleolar Precursor Body (NPB). But the NPB is also required for the organisation
of the zygotic heterochromatin and the establishment of pluripotency. We found
that disruption of the mouse Upstream Binding Factor (UBF (UBTF)) gene caused
disassembly of somatic nucleoli and the accumulation of the key rRNA gene
transcription factors into dense subnuclear foci resembling NPBs. Here we show
that UBF deletion causes the rRNA genes to collapse onto their centromere
proximal chromosomal sites spatially distinct from NPB-like structures, and that
these structures contain rRNA gene transcription factors but not all nucleolar
proteins. We further find that embryonic NPBs and their surrounding
heterochromatin are both disrupted in UBF-null mouse embryos. These embryos also
display subnuclear foci containing the rRNA gene transcription factors and arrest
development before completing the forth cleavage division. The data suggest that
the rRNA gene transcription factors have an intrinsic ability to interact and
form a discrete nuclear compartment even in the absence of any rRNA gene activity
and that the formation or maintenance of the zygotic NPB and surrounding
heterochromatin requires UBF.
PMID- 27614296
TI - Subset geometric phase analysis method for deformation evaluation of HRTEM
images.
AB - Geometrical phase analysis (GPA) is typically a powerful tool to investigate the
deformation in high resolution transmission electron microscopy images and has
been used in various fields. The traditional GPA method using the fast Fourier
transform, referred to as global-GPA (G-GPA) here, is based on the relationship
between the displacement and the phase difference. In this paper, a subset-GPA (S
GPA) is introduced for further improvement. The S-GPA performs the windowed
Fourier transform block by block in the image. The maximum strain measurement
scale of the GPA method is theoretically analyzed on the basic of the phase
spectrum extraction process. The upper limit is one third of the atomic spacing.
The results of various numerical simulations verified that the S-GPA method
performs better than the traditional G-GPA method in both the homogeneous and
inhomogeneous deformation conditions, with the evaluation parameter of
calculation reliability of S-GPA 10% higher than G-GPA. Specifically, the
measurement accuracy of S-GPA is about three times higher than the G-GPA when
calculating small strain (less than 2000MUepsilon). For the large strain (greater
than 150000MUepsilon), the measurement accuracy of S-GPA is about 50% higher than
that of the G-GPA. Besides, the S-GPA method can significantly eliminate the
phase filling effect, while the G-GPA cannot. The S-GPA method has been
successfully applied to analyze the strain field distribution in an lnGaAs/InAlAs
supperlattice heterostructure.
PMID- 27614295
TI - Next-generation electron microscopy in autophagy research.
AB - Autophagy is the process whereby cytosol, organelles, and inclusions are taken up
in a double-membrane vesicle known as the autophagosome, and transported to the
lysosome for destruction and recycling. Electron microscopy (EM) led to the
discovery of autophagy in the 1950s and has been a central part of its
characterization ever since. New capabilities in single particle EM studies of
the autophagy machinery are beginning to provide exciting insights into the
mechanisms of autophagosome initiation, growth, and substrate targeting. These
include EM structures at various resolutions of part of the Atg1 protein kinase
complex and all of the class III phosphatidylinositol 3-phosphate complex I that
initiate autophagy; the mTORC1 complex that regulates autophagy initiation; the
Ape1 particle, a major substrate for selective autophagy in yeast; and p62, a
mammalian selective autophagy adaptor. Equally exciting are the prospects for
increased resolution and insight into autophagosome formation in cells from
advances in cryo-EM tomography and focused ion beam-scanning electron microscopy
(FIB-SEM). This review considers recent accomplishments, prospects for progress,
and remaining obstacles that still need to be overcome.
PMID- 27614297
TI - Three dimensional mapping of Fe dopants in ceria nanocrystals using direct
spectroscopic electron tomography.
AB - Electron tomography is a powerful technique for the 3D characterization of the
morphology of nanostructures. Nevertheless, resolving the chemical composition of
complex nanostructures in 3D remains challenging and the number of studies in
which electron energy loss spectroscopy (EELS) is combined with tomography is
limited. During the last decade, dedicated reconstruction algorithms have been
developed for HAADF-STEM tomography using prior knowledge about the investigated
sample. Here, we will use the prior knowledge that the experimental spectrum of
each reconstructed voxel is a linear combination of a well-known set of
references spectra in a so-called direct spectroscopic tomography technique.
Based on a simulation experiment, it is shown that this technique provides
superior results in comparison to conventional reconstruction methods for
spectroscopic data, especially for spectrum images containing a relatively low
signal to noise ratio. Next, this technique is used to investigate the spatial
distribution of Fe dopants in Fe:Ceria nanoparticles in 3D. It is shown that the
presence of the Fe2+ dopants is correlated with a reduction of the Ce atoms from
Ce4+ towards Ce3+. In addition, it is demonstrated that most of the Fe dopants
are located near the voids inside the nanoparticle.
PMID- 27614298
TI - A REVIEW OF THE FUNDAMENTAL PRINCIPLES OF RADIATION PROTECTION WHEN APPLIED TO
THE PATIENT IN DIAGNOSTIC RADIOLOGY.
AB - A review of the role and relevance of the principles of radiation protection of
the patient in diagnostic radiology as specified by ICRP has been undertaken when
diagnostic risks arising from an examination are taken into account. The increase
in population doses arising from diagnostic radiology over the past 20 years has
been due to the widespread application of higher dose CT examinations that
provide significantly more clinical information. Consequently, diagnostic risks
as well as radiation risks need to be considered within the patient radiation
protection framework. Justification and optimisation are discussed and the
limitations imposed on patient protection by employing only a radiation risk
framework is highlighted. The example of radiation protection of the patient in
breast screening programmes employing mammography is used to highlight the
importance of defined diagnostic outcomes in any effective radiation protection
strategy.
PMID- 27614299
TI - Definition of Local Diagnostic Reference Levels in a Radiology Department Using a
Dose Tracking Software.
AB - Dose optimization in radiological examinations is a mandatory issue: in this
study local Diagnostic Reference Levels (lDRLs) for Clinical Mammography (MG),
Computed Tomography (CT) and Interventional Cardiac Procedures (ICP) performed in
our Radiology Department were established. Using a dose tracking software, we
have collected Average Glandular Dose (AGD) for two clinical mammographic units;
CTDIvol, Size-Specific Dose Estimate (SSDE), Dose Length Product (DLP) and total
DLP (DLPtot) for five CT scanners; Fluoro Time, Fluoro Dose Area Product (DAP)
and total DAP (DAPtot) for two angiographic systems. Data have been compared with
Italian Regulation and with the recent literature. The 75th percentiles of the
different dosimetric indices have been calculated. Automated methods of radiation
dose data collection allow a fast and detailed analysis of a great amount of data
and an easy determination of lDRLs for different radiological procedures.
PMID- 27614294
TI - The role of laminins in the organization and function of neuromuscular junctions.
AB - The synapse between motor neurons and skeletal muscle is known as the
neuromuscular junction (NMJ). Proper alignment of presynaptic and post-synaptic
structures of motor neurons and muscle fibers, respectively, is essential for
efficient motor control of skeletal muscles. The synaptic cleft between these two
cells is filled with basal lamina. Laminins are heterotrimer extracellular matrix
molecules that are key members of the basal lamina. Laminin alpha4, alpha5, and
beta2 chains specifically localize to NMJs, and these laminin isoforms play a
critical role in maintenance of NMJs and organization of synaptic vesicle release
sites known as active zones. These individual laminin chains exert their role in
organizing NMJs by binding to their receptors including integrins, dystroglycan,
and voltage-gated calcium channels (VGCCs). Disruption of these laminins or the
laminin-receptor interaction occurs in neuromuscular diseases including Pierson
syndrome and Lambert-Eaton myasthenic syndrome (LEMS). Interventions to maintain
proper level of laminins and their receptor interactions may be insightful in
treating neuromuscular diseases and aging related degeneration of NMJs.
PMID- 27614301
TI - Implementation fidelity for promoting the effectiveness of an adolescent sexual
health program.
AB - The goal of the present study was to examine COMPAS program (Competencies for
adolescents with a healthy sexuality) outcomes based on implementation fidelity:
dose, adherence, and acceptance. Participants were 716 adolescents aged 14-16
years (46.5% boys). Two fidelity groups were established: high (n=83) and low
(n=312), with the remaining sample serving as a non-program control group
(n=321). Knowledge about sexually transmitted infections (STIs), attitudes
towards HIV, intention to use condoms, and sexual behavior were evaluated.
Results indicated that adolescents receiving the intervention displayed improved
STI knowledge (p<0.001) and improved attitudes toward HIV (p<0.05) as compared to
the control group. Between the two intervention groups, a high-fidelity group
intended to engage more in safe sex behaviors (p=0.05) and displayed greater STI
knowledge (p=0.05) as compared to the low-fidelity group. The present study
revealed improved efficiency when applying prevention programs with
implementation fidelity.
PMID- 27614300
TI - Instrumental-Variables Simultaneous Equations Model of Physical Activity and Body
Mass Index: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.
AB - We used full-system-estimation instrumental-variables simultaneous equations
modeling (IV-SEM) to examine physical activity relative to body mass index (BMI;
weight (kg)/height (m)(2)) using 25 years of data (1985/1986 to 2010/2011) from
the Coronary Artery Risk Development in Young Adults (CARDIA) Study (n = 5,115;
ages 18-30 years at enrollment). Neighborhood environment and sociodemographic
instruments were used to characterize physical activity, fast-food consumption,
smoking, alcohol consumption, marriage, and childbearing (women) and to predict
BMI using semiparametric full-information maximum likelihood estimation to
control for unobserved time-invariant and time-varying residual confounding and
differential measurement error through model-derived discrete random effects.
Comparing robust-variance ordinary least squares, random-effects regression,
fixed-effects regression, single-equation-estimation IV-SEM, and full-system
estimation IV-SEM, estimates from random- and fixed-effects models and the full
system-estimation IV-SEM were unexpectedly similar, despite the lack of control
for residual confounding with the random-effects estimator. Ordinary least
squares tended to overstate the significance of health behaviors in BMI, while
results from single-equation-estimation IV-SEM were notably different, revealing
the impact of weak instruments in standard instrumental-variable methods. Our
robust findings for fixed effects (which does not require instruments but has a
high cost in lost degrees of freedom) and full-system-estimation IV-SEM (vs.
standard IV-SEM) demonstrate potential for a full-system-estimation IV-SEM method
even with weak instruments.
PMID- 27614302
TI - The Effect of Antiemetics and Antihistamines on the QTc Interval in Emergent
Dialysis Patients With Baseline QTc Prolongation.
AB - BACKGROUND: Unfunded patients with end-stage renal disease (ESRD) who do not have
routinely scheduled hemodialysis often receive medications known to prolong the
QTc interval for their uremic symptoms even though they may have pre-existing QTc
prolongation. OBJECTIVES: The purpose of this study was to determine the effects
of these medications on the QTc interval in these patients. METHODS: Unfunded
patients with ESRD presenting to the emergency department (ED) for emergent
hemodialysis (HD) with QTc prolongation on their initial electrocardiogram (ECG)
were recruited. Approximately 2 hours after receiving an antihistamine or
antiemetic, a second ECG was ordered and the QTc was measured. The patients were
followed-up 1 week later. RESULTS: Twenty-nine percent (44/152) of the unfunded
patients with ESRD presenting for HD at a county hospital had QT prolongation and
were included with 107 total ED visits during the 4-week study period. The mean
QTc was 483.7 msec on presentation to the ED, and the mean QTc measured 2 hours
after receiving an antihistamine or antiemetic was 483.8 msec. None of the
patients were admitted for life-threatening dysrhythmias. Thirty-six percent
(16/44) of the recruited patients had QTc intervals >500 msec with a combined
total of 31 patient visits, of which only 25.8% (8/31) had an increase in the QTc
interval after an antihistamine or antiemetic medication was given. None of these
patients had adverse outcomes, such a dysrhythmia or death, at 1-week follow-up.
CONCLUSION: This study shows that medications known to cause QTc prolongation are
safe to use in therapeutic doses in patients with ESRD who have pre-existing QT
prolongation. Few patients in this cohort had significantly prolonged QTc
intervals at baseline.
PMID- 27614303
TI - National Trends in Emergency Department Visits by Adults With Mental Health
Disorders.
AB - BACKGROUND: Although mental health disorders (MHDs) affect as many as 1 in 4
adults in the U.S., the national trends in emergency department (ED) use for
adults who have MHD comorbidities are unknown. OBJECTIVE: To evaluate the role of
mental health disorder co-morbidities for adults who use the ED and how this
utilization differs by insurance type. METHODS: This is a retrospective analysis
of the National Emergency Department Survey (NEDS) dataset of adults 18 to 64
years of age that was conducted from 2006 to 2011. We defined individuals with
MHD comorbidities by applying the MHD Clinical Classification Software groupings
to any of the 1 to 15 diagnostic fields available in the NEDS. We further
evaluated ED visits made for a primary diagnosis of MHD by applying the same
aforementioned codes to the primary diagnosis. We constructed ED visit rates
using the U.S. Census Bureau's Current Population Survey. We used descriptive
statistics and tested for differences in trends in visits and visit rates by
payer using an ordinary least squares regression. RESULTS: The number of ED
visits increased by 8.6% from 2006 to 2011. The number of ED visits made by
adults primarily for MHDs and with MHD comorbidities increased by 20.5% and
53.3%, respectively (p < 0.0001); ED visits made adults without MHDs decreased by
1.1% (p = 0.72) for the same time period. When accounting for the population
growth rate, ED visit rates made by adults with MHD comorbidities increased for
all insurance types, but decreased for those without MHD comorbidities.
CONCLUSION: MHD comorbidities play a significant role in the increasing number of
ED visits, regardless of insurance coverage. Additional studies are needed to
understand the role of patients with MHDs and ED use.
PMID- 27614304
TI - Erratum.
PMID- 27614305
TI - Erratum.
PMID- 27614306
TI - Erratum.
PMID- 27614307
TI - Erratum.
PMID- 27614308
TI - Occult Lung Cancer Occluding a Pulmonary Vein with Suspected Venous Infarction,
Mimicking Pneumonia and a Pulmonary Embolus.
AB - BACKGROUND: Patients with lung cancer present to the emergency department (ED) in
a variety of ways. Symptoms are often nonspecific and can lead to a delay in
diagnosis. Here, a lung cancer mimicked two illnesses, adding to the diagnostic
complexity. This case highlights diagnostic pitfalls as well as advantages and
limitations of imaging utilized in the emergency setting. CASE REPORT: We report
a case of an occult lung cancer occluding a pulmonary vein, which at first
mimicked pneumonia and later a pulmonary embolism (PE) and arterial lung
infarction. The patient presented to the ED with cough and a lung opacity on
chest radiograph that was treated with antibiotics. However, recurrent visits to
the ED with similar complaints were further investigated with computed tomography
angiogram (CTA). At first the scan was considered positive for PE. Further
inspection revealed that the CTA findings were not typical for PE, but rather a
slow flow state likely caused by an occult mass occluding a pulmonary vein with
venous infarction. Biopsy revealed a lung adenocarcinoma. In addition to the case
presentation, the typical signs of PE on CTA with correlating images and
diagnostic pitfalls are discussed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
THIS?: This case report raises two themes that can be of interest to emergency
physicians. The first is that lung cancer has many guises. Here it mimicked two
distinctly different diseases, pneumonia and PE. The second is that, although CTA
is highly sensitive and specific for diagnosing PE, it has limitations that may
lead to false positive readings. When clinical signs and symptoms fail to
correlate with the imaging diagnosis, alternative explanations should be sought.
PMID- 27614309
TI - In Response To: The Bedside Ultrasound: A Rapid Way of Measuring Optic Nerve
Sheath Diameter in Emergency Medicine.
PMID- 27614310
TI - SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling.
AB - Dexamethasone (Dex) causes osteoblast cell injuries. In the present research, we
tested the potential effect of SC79, a novel and specific Akt activator, against
Dex in osteoblasts. In primary murine osteoblasts and osteoblastic MC3T3-E1
cells, pretreatment with SC79 significantly attenuated Dex-induced cell death.
Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening,
cytochrome C release and apoptosis activation were dramatically alleviated with
SC79 pretreatment in above cells. At the molecular level, SC79 activated Akt,
which was indispensable for subsequent osteoblast protection against Dex. Akt
inhibitors (LY294002, perifosine and MK-2206) blocked SC79-induced Akt activation
and abolished its anti-Dex actions in osteoblasts. Further, SC79 activated Akt
downstream Nrf2 (NF-E2-related factor 2) signaling and attenuated Dex-induced
oxidative stress in osteoblasts. Nrf2 shRNA knockdown or S40T mutation almost
reversed SC79-mediated anti-oxidant and cytoprotective activities in osteoblasts.
Together, these results suggest that SC79 activates Akt-Nrf2 signaling to protect
osteoblasts from Dex.
PMID- 27614311
TI - Improved transduction efficiencies of adeno-associated virus vectors by synthetic
cell-permeable peptides.
AB - Various serotypes of adeno-associated virus (AAV) vectors have been used for gene
therapy and as research tools. Among these serotypes, the AAV type 2 vector has
been used successfully in human gene therapies. However, the transduction
efficiency of AAV2 depends on the cell type, and this poses a problem in the
efficacy of gene therapy. To improve the transduction efficiency of AAV2, we
designed a small peptide consisting of epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor peptide and the HIV-Tat sequence Tat-Y1068. Pre- or co
treatment of CYNOM-K1 cells from cynomolgus monkey embryo skin with Tat-Y1068
increased the transduction efficiencies in a dose-dependent manner and caused p38
phosphorylation. The transduction efficiency of AAV2 into the rat fibroblast cell
line RAT-1 highly expressing EGFR was less than the transduction efficiency of
AAV2 into CYNOM-K1 cells. Tat-Y1068 increased the transduction efficiency in RAT
1 cells in the same manner as in CYNOM-K1 cells. In conclusion, cell-permeable
peptides possessing the EGFR tyrosine kinase inhibitor function might serve as a
useful ingredient of AAV2 vector solution for increasing the transduction
efficiency of gene therapies.
PMID- 27614312
TI - Molecular cloning and expression analysis of cytochrome c oxidase subunit II from
Sitophilus zeamais.
AB - Cytochrome c oxidase subunit II (COX II) containing a dual core CuA active site
is one of the core subunits of mitochondrial Cytochrome c oxidase (Cco), which
plays a significant role in the physiological process. In this report, the full
length cDNA of COXII gene was cloned from Sitophilus zeamais, which had an open
reading frame (ORF) of 684 bp encoding 227 amino acids residues. The predicted
COXII protein had a molecular mass of 26.2 kDa with pI value of 6.37. multiple
sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais
COXII had high sequence identity with the COXII of other insect species. The gene
was subcloned into the expression vector pET-32a, and induced by isopropyl beta-d
thiogalactopyranoside (IPTG) in E. coli Transetta (DE3) expression system.
Finally the recombinant COXII with 6-His tag was purified using affinity
chromatography with Ni(2+)-NTA agarose. Western Blotting (WB) showed the
recombinant protein was about 44 kD, and the concentration of fusion protein was
50 MUg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that
recombinant COXII could catalyze the oxidation of substrate Cytochrome C (Cyt c),
and influenced by allyl isothiocyanate (AITC). By using molecular docking method,
It was found that a sulfur atom of AITC structure could form a length of 2.9 A
hydrogen bond with Leu-31. These results suggested that tag-free COXII was
functional and one of the action sites of AITC, which will be helpful to carry
out a point mutation in binding sites for the future research.
PMID- 27614313
TI - Sulfur dioxide inhalation lowers sperm quality and alters testicular histology
via increasing expression of CREM and ACT proteins in rat testes.
AB - Sulfur dioxide (SO2) is one of the main atmospheric pollutants worldwide, and is
reported to be responsible for the formation of severe haze in China. Some
studies have demonstrated a potential harmful effect of SO2 on the male
reproductive system; however the underlying mechanism is still unknown. The
purpose of this study is to investigate the roles of cytochrome P450 (P450), cAMP
responsive element modulator (CREM), and activator of CREM (ACT) in SO2-induced
toxicity. Forty-eight male Wistar rats were randomly divided into an experimental
and control group. The experiment group was exposed to SO2 in ambient air (10ppm,
4h/day), and the control group was treated with filtered air in the same
conditions. After 2 weeks, the results showed a significant decrease in body
weight and sperm motility, and an increase in the testis weight-to-body weight
ratio as compared to the control group. Histological investigation suggested that
SO2 exposure led to loose arrangement of the spermatogenic cells and local
structural damage in the seminiferous tubules. Moreover, the expressions of P450,
CREM and ACT proteins increased in the testes by 0.22%, 47.26% and 23.38%,
respectively. Taken together, SO2 inhalation lowered sperm quality, altered
testicular histology, and increased expressions of CREM and ACT proteins in the
testes of rats. Overall, these results could contribute to a better understanding
of SO2-induced male reproductive toxicity.
PMID- 27614314
TI - Self-perceived competence and social acceptance of young children who stutter:
Initial findings.
AB - PURPOSE: The goals of this study were to determine whether young children who
stutter (CWS) perceive their own competence and social acceptance differently
than young children who do not stutter (CWNS), and to identify the predictors of
perceived competence and social acceptance in young speakers. METHOD: We
administered the Pictorial Scale of Perceived Competence and Social Acceptance
for Young Children (PSPCSA; Harter & Pike, 1984) to 13 CWS and 14 CWNS and
examined group differences. We also collected information on the children's
genders, temperaments, stuttering frequencies, language abilities, and
phonological skills to identify which of these factors predicted PSPCSA scores.
RESULTS: CWS, as a group, did not differ from CWNS in their perceived general
competence or social acceptance. Gender predicted scores of perceived general
competence, and stuttering frequency predicted perceived social acceptance.
Temperament, language abilities, and phonological skills were not significant
predictors of perceived competence or social acceptance in our sample.
CONCLUSIONS: While CWS did not significantly differ from CWNS in terms of
perceived competence and social acceptance, when both talker groups were
considered together, girls self-reported greater perceived competence than boys.
Further, lower stuttering frequency was associated with greater perceived social
acceptance. These preliminary findings provide motivation for further empirical
study of the psychosocial components of childhood stuttering. LEARNING OUTCOMES:
Readers will be able to describe the constructs of perceived competence and
social acceptance in young children, and whether early stuttering plays a role in
the development of these constructs.
PMID- 27614315
TI - Chondroitin sulphate inhibits NF-kappaB activity induced by interaction of
pathogenic and damage associated molecules.
AB - OBJECTIVE: To evaluate the anti-inflammatory mechanism of action of Chondroitin
Sulphate (CS). DESIGN: THP-1 macrophages were cultured with a range of sizes and
concentrations of HA fragments with TLR4 (LPS in a physiologically relevant
concentration determined by analyses of sera of a community clinic ascertained
knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists
and varying concentrations of CS in a physiologically relevant range (10-200
MUg/ml). We measured IL-1beta release, intracellular IL-1beta, proIL-1beta,
caspase-1 and NF-kappaB activity and DNA binding activity of NF-kappaB
transcription factors from nuclear and cytoplasmic extracts. RESULTS: Serum LPS
was significantly associated with radiographic knee joint space narrowing (JSN)
(P = 0.02) in the OA cohort (n = 40). The priming dose of LPS used for these
experiments (10 ng/ml) was below the lowest serum concentration of the OA cohort
(median 47.09, range 14.43-81.36 ng/ml). Priming doses of LPS and HA fragments
alone did not elicit an inflammatory response. However, primed with LPS, HA
fragments produced large dose-dependent increases in IL-1beta that were
inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically
achievable concentrations, attenuated NF-kappaB activity induced by either the
TLR4 (LPS 1000 ng/ml) or TLR2 agonists alone or in combination with HA fragments.
LPS induced and CS significantly reduced activity of canonical NF-kappaB
transcription factors, p65, p50, c-Rel and RelB. CONCLUSIONS: Subinflammatory
concentrations of pathogenic (LPS, listeria) and damage associated (HA) molecules
interact to induce macrophage-related inflammation. CS works upstream of the
inflammasome by inhibiting activation of NF-kappaB transcription factors.
PMID- 27614316
TI - Decreased expression of GLUT4 in male CG-IUGR rats may play a vital role in their
increased susceptibility to diabetes mellitus in adulthood.
AB - Rats with intrauterine growth retardation and catch-up growth (CG-IUGR) after
birth show increased susceptibility to diabetes mellitus in adulthood. The
expression of glucose transporter type 4 (GLUT4) decreases in female IUGR
offspring rats with seminutrient restriction during pregnancy. However, the male
CG-IUGR rats also display an increased susceptibility to diabetes mellitus in
adulthood. Whether there is another factor, besides GLUT4, in male CG-IUGR rat
that mediates their susceptibility to diabetes mellitus? The male IUGR rats with
catch-up growth were selected as the research objects. CG-IUGR rats had an
increased fasting blood glucose level, and increased serum total cholesterol,
triglyceride and free fatty acid levels. Glucose tolerance test and insulin
tolerance test showed higher glucose levels and much higher insulin levels after
a glucose load in CG-IUGR. The mRNA and protein expressions of IRS-2 in liver
tissue, and IRS-1 and GLUT4 in skeletal muscle in CG-IUGR rats were down
regulated, but only the GLUT4 down-regulation displayed strong negative
correlations with the decreased glucose tolerance capability by Pearson's
analysis. The methylation patterns of CpG islands in the promoter regions of IRS
1, IRS-2 and GLUT4 in CG-IUGR rats varied, which was not significantly correlated
with their expressions. The male CG-IUGR rats showed decreased glucose tolerant
capability, suggesting increased susceptibility to diabetes mellitus in
adulthood. The GLUT4 down-regulation may play a vital role in the development of
decreased glucose tolerance in male CG-IUGR rats. The methylation modification of
the promoter region of GLUT4 does not appear to be involved in its expression.
PMID- 27614317
TI - Gender difference in valproic acid-induced neuroprotective effects on APP/PS1
double transgenic mice modeling Alzheimer's disease.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive
memory and cognitive impairment with gender difference in specific cognitive
ability domains, pathology, and risk of AD. Since valproic acid (VPA) is a widely
used mood stabilizer and an antiepileptic drug, which exhibits multiple
neuroprotective activities on AD, this study intended to investigate the gender
difference in the effect of VPA on APP/PS1 double transgenic mice modeling AD.
Behavioral experiments showed that VPA reduced the autonomous behaviors, improved
learning and memory, and exhibited gender differences in AD mice compared with
the control mice. The decrease in senile plaque, amyloid beta (Abeta) 40, and
Abeta42 caused by VPA in the male AD mice was more notable than that in the
female AD mice. Meanwhile, VPA protected brain cells from dying notably in the
male AD mice but only slightly in the female AD mice, and VPA treatment thickened
the postsynaptic density and markedly increased the number and density of
presynaptic vesicles in both male and female AD mice. However, the effects of
rescuing early synaptic structural and functional deficits by VPA were more
obvious in the male mice. Overall, these results supported the hypothesis that
gender difference significantly influences AD and indicated that VPA may be a
promising remedy for AD if basic biological differences and gender specificity
were prudently taken into account.
PMID- 27614318
TI - A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of
Lubricin (150 MUg/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops
(Vismed(r)) in Patients with Moderate Dry Eye Disease.
AB - PURPOSE: The objective of this clinical trial (NCT02507934) was to assess the
efficacy and safety of recombinant human lubricin as compared to a 0.18% sodium
hyaluronate (HA) eye drop in subjects with moderate dry eye disease (DED).
METHODS: DEWS Grade 2-3 subjects were randomized to use lubricin (N=19, 51.9 +/-
11.8 years) or HA (N=20, 61.8 +/- 13.3 years). After a saline washout period,
subjects administered BID therapy for 7 days, followed by instillation as needed
(2-6 drops per eye) for 7 days. Visual analog scale (VAS) including foreign body
sensation, burning/stinging, itching, pain, sticky feeling, blurred vision and
photophobia were primary outcomes, with secondary endpoints of corneal
fluorescein staining, Schirmer test, tear film breakup time (TFBUT), eyelid and
conjunctival erythema and number of instillations compared at day 14. RESULTS:
The primary endpoint was met. Lubricin supplementation achieved greater than a
72% reduction from baseline in foreign body sensation (P<.013), burning/stinging,
pain, sticky feeling (P<.0432), blurred vision (P<.0013), and photophobia
(P<.011) in at least one eye. Lubricin also showed significant improvement in
fluorescein staining (OD/OS: 43.8%/50.0%, vs. 26.5%/23.3%, P<.0398, P<.0232),
TFBUT (P<.010), SANDE frequency (P<.0435), eyelid erythema (P<.004), conjunctival
erythema (P<.0013), and instillations (P<.04) as compared to HA. No treatment
related adverse events occurred during the investigation. CONCLUSIONS:
Recombinant human lubricin was shown to produce significant improvement in both
signs and symptoms of dry eye disease as compared to HA.
PMID- 27614319
TI - Simultaneous detection of Zika, Chikungunya and Dengue viruses by a multiplex
real-time RT-PCR assay.
AB - BACKGROUND: In the recent past, arboviruses such as Chikungunya (CHIKV) and Zika
(ZIKV) have increased their area of endemicity and presented as an emerging
global public health threat. OBJECTIVES: To design an assay for the simultaneous
detection of ZIKV, CHIKV and Dengue (DENV) 1-4 from patients with symptoms of
arboviral infection. This would be advantageous because of the similar clinical
presentation typically encountered with these viruses and their co-circulation in
endemic areas. STUDY DESIGN: In this study we have developed and validated a
triplex real time reverse transcription PCR assay using hydrolysis probes
targeting the non-structural 5 (NS5) region of ZIKV, non-structural protein 4
(nsP4) from CHIKV and 3' untranslated region (3'UTR) of DENV 1-4. RESULTS AND
CONCLUSIONS: The 95% LOD by the triplex assay was 15 copies/reaction for DENV-1
and less than 10 copies/reaction for all other viruses. The triplex assay was
100% specific and did not amplify any of the other viruses tested. The assay was
reproducible and adaptable to testing different specimen types including serum,
plasma, urine, placental tissue, brain tissue and amniotic fluid. This assay can
be easily implemented for diagnostic testing of patient samples, even in a high
throughput laboratory.
PMID- 27614320
TI - Chromium immobilization in soil using quaternary ammonium cations modified
montmorillonite: Characterization and mechanism.
AB - The potential risk of heavy metal in soil can be reduced by stabilization
techniques. Stabilizing amendments, montmorillonites modified with
tetramethylammonium (TMA) and hexadecyltrimethylammonium (HDTMA) at different
loadings were prepared, characterized and assayed for remediation of hexavalent
chromium contaminated soil. Characterization results demonstrated that TMA
modification resulted in increased surface area and pore volume, whereas HDTMA
modification resulted in decreased surface area and pore volume. For HDTMA
modified montmorillonites (H-Monts), the arrangement model of surfactant
molecules and the structural characteristics strongly depended on the surfactant
loading density. Less pronounced packing density dependence was observed for TMA
modified montmorillonites (T-Monts). Modified toxicity characteristic leaching
procedure (TCLP) was utilized to evaluate the chromium immobilizing capacity of
the prepared organo-montmorillonites, and the results revealed that both T-Monts
and H-Monts can be reasonably effective in chromium stabilization under different
leaching condition. The comparison of chromium leaching behavior manifested by T
Monts and H-Monts suggested that mechanisms for chromium immobilization by organo
montmorillonites amendment proceeded via two adsorption approaches. Each approach
involves different functional groups, depending on the leaching pH and surfactant
loading concentration. In addition, the effect of HDTMA loading concentration,
amendment dosage, initial chromium concentration and incubation time on the
immobilizing efficiency of H-Monts was investigated.
PMID- 27614321
TI - Effects of thiocyanate on granule-based anammox process and implications for
regulation.
AB - The feasibility of using anaerobic ammonium oxidation (anammox) process to treat
industrial wastewater containing thiocyanate (SCN-) was examined in this study.
Anammox activity decreased with increasing thiocyanate concentration and pre
exposure time in batch tests. A typical noncompetitive model was used to fit the
data for thiocyanate inhibition, and the 50% inhibition concentration (IC50) of
thiocyanate on anammox was 620.4mgL-1 at 200mgL-1 total nitrogen level. The
influent thiocyanate concentration of test reactor (R1) in phase II gradually
increased from 10 to 120mgL-1, and the average nitrogen removal efficiency (NRE)
of R1 was maintained at 83.0+/-7.82%. This robustness was attributed to the self
adaptation ability of anammox biomass through long-term acclimatization. The NRE
was decreased to 57.1% under 130mgL-1 thiocyanate within two days. However, the
NRE of control reactor (R0) in absence of thiocyanate was 91.23+/-4.11% in this
phase. Under thiocyanate stress, the specific anammox activity, settling velocity
and heme c content of the granules significantly decreased, and the extracellular
polymeric substances content slightly increased. The short- and long-term
performance inhibition could be reversed in the presence of 10mgL-1 Fe(III).
PMID- 27614322
TI - Rice husks as a sustainable silica source for hierarchical flower-like metal
silicate architectures assembled into ultrathin nanosheets for adsorption and
catalysis.
AB - Metal silicates have attracted extensive interests due to their unique structure
and promising properties in adsorption and catalysis. However, their applications
were hampered by the complex and expensive synthesis. In this paper, three
dimensional (3D) hierarchical flower-like metal silicate, including magnesium
silicate, zinc silicate, nickel silicate and cobalt silicate, were for the first
time prepared by using rice husks as a sustainable silicon source. The flower
like morphology, interconnected ultrathin nanosheets structure and high specific
surface area endowed them with versatile applications. Magnesium silicate was
used as an adsorbent with the maximum adsorption capacities of 557.9, 381.3, and
482.8mg/g for Pb2+, tetracycline (TC), and UO22+, respectively. Ni
nanoparticles/silica (Ni NPs/SiO2) exhibited high catalytic activity and good
stability for 4-nitrophenol (4-NP) reduction within only ~160s, which can be
attributed to the ultra-small particle size (~6.8nm), good dispersion and high
loading capacity of Ni NPs. Considering the abundance and renewability of rice
husks, metal silicate with complex architecture can be easily produced at a large
scale and become a sustainable and reliable resource for multifunctional
applications.
PMID- 27614323
TI - Selective adsorption behavior of Cd(II) ion imprinted polymers synthesized by
microwave-assisted inverse emulsion polymerization: Adsorption performance and
mechanism.
AB - Microwave-assisted inverse emulsion polymerization method was used to prepare
Cd(II) imprinted polymer (IIP) by using beta-cyclodextrin (beta-CD) and
acrylamide (AM) as functional monomer, epichlorohydrin (ECH) as crossing-linking
agent, ammonium persulfate as initiator. The Cd(II) imprinted polymer was
characterized by SEM, FTIR and TGA. The influences of initial concentration of
Cd(II), pH values, temperature, time and competitive ions on adsorption capacity
and recognition properties are investigated. Under the optimal conditions, the
adsorption capacity could reach 107mg/g. Furthermore, pseudo first order kinetic
model, pseudo second order kinetic model and intra-particular diffusion model
were used to describe the adsorption kinetic behavior. Results showed that the
pseudo-second-order model (R2 0.9928-0.9961) had the best agreement with the
experimental data. Langmuir adsorption isotherm model described the experimental
data well, which indicated that adsorption was mainly monolayer absorption.
Moreover, the study of adsorption thermodynamics (DeltaG0<0, DeltaH0>0,
DeltaS0>0) suggested that the adsorption process was a spontaneous and
endothermic process. Competitive selectivity experiment revealed that imprinted
polymer could selectively recognize Cd(II). It provides a new idea for removing
Cd(II) from aqueous solution.
PMID- 27614324
TI - Layered double hydroxide intercalated with aromatic acid anions for the efficient
capture of aniline from aqueous solution.
AB - Aniline is toxic and hard to be degraded, and thereby causes the environmental
pollution seriously. Herein, a practical and green hydrothermal method was
applied to fabricate terephthalic acid and pyromellitic acid intercalated layered
double hydroxides (LDH) (named as TAL and PAL) for aniline efficient removal. The
sorption of aniline on LDH-based materials were investigated at different
experimental conditions, and the results indicated that aniline sorption on LDH,
TAL and PAL were strongly dependent on pH and independent of ionic strength. The
maximum sorption capacities of aniline on TAL and PAL at pH 5.0 and 293K were
90.4 and 130.0mg/g, respectively, which were significantly higher than that of
aniline on LDH (52.6mg/g). Based on the BET, FTIR and XPS analysis, the higher
sorption capacities of TAL and PAL were mainly due to high surface area and basal
spacing as well as the abundant functional groups (e.g. -COO-). The interactions
of aniline with TAL and PAL were mainly dominated by hydrogen bonds and
electrostatic interactions. Such a facile synthesis method, efficient removal
performance and superior reusability indicated that the aromatic acid modified
LDH materials had potential application for efficient treatment of organic
pollutants in environmental pollution cleanup.
PMID- 27614325
TI - Identification of novel signature genes attesting arsenic-induced immune
alterations in adult zebrafish (Danio rerio).
AB - Arsenic poisoning is a serious global issue. Apart from causing developmental and
systemic toxicity, arsenic has recently been reported for its ability to hinder
immune responses. The present study is designed to identify the global expression
profile associated with arsenic-induced immune alterations at the organismic
level. Adult zebrafish (Danio rerio) were exposed to 20, 40 and 80ppb of arsenic
trioxide for 30days, sacrificed and global gene expression profile studied.
Microarray data suggested 65 immune related genes were commonly affected in the
three treatment regimens. The expression profile of key immune related genes
(tlr1, nitr1f, nitr1c, crfb8, socs7, socs3b, abcb3/1, mch1uja, ifngamma1-2,
cxcl12b and crlf1a) was validated by qPCR. Pathway analysis suggested the major
involvement of JAK-STAT circuit in the process. The expression of these marker
genes was also studied in arsenic exposed and bacteria (Aeromonas hydrophila)
challenged zebrafish. Increase in bacterial colony forming units (CFU) coupled
with gross histopathology of kidney in arsenic exposed-bacteria challenged fish
suggested profound immuno-compromised condition. We propose that chronic arsenic
exposure leads to hyperactivation of the immune system as a consequence when
exposed to further stress (microbial) it induces immuno-suppression with
pathological implications. The study provides a molecular snap shot for
predicting arsenic immuno-toxicity.
PMID- 27614326
TI - Carbonization of heavy metal impregnated sewage sludge oriented towards potential
co-disposal.
AB - Sewage sludge (SS) is adopted as a stabilizer to immobilize externally
impregnated heavy metals through carbonization oriented towards the co-disposal
of SS and some hazardous wastes. Firstly Cu and Pb were impregnated into SS to
ascertain the impregnating capacity and leaching behaviours of heavy metals in
the resulting sewage sludge char (SSC). Meanwhile, scanning electron microscopy
(SEM) and X-ray diffraction (XRD) were employed to detect the heavy metal phase
in the SSC. The results showed that within 400-800 degrees C and an impregnating
concentration ?0.5wt%, more than 90% of the externally impregnated Cu and Pb were
remained in the SSC and immobilized. And higher temperatures helped produce non
hazardous SSC. In addition, SEM and XRD analyses revealed that externally
impregnated heavy metals could be converted into stable forms and evenly
distributed throughout the SSC. In the second step municipal solid waste
incineration fly ash (FA) was kneaded into SS and subjected to carbonization; it
has been proved that the heavy metals in FA can be well immobilized in the
resulting char when FA: SS mass ratio is 1:5. Those results show that sewage
sludge can be co-carbonized with wastes contaminated with heavy metals to achieve
co-disposal.
PMID- 27614327
TI - Variability in findings of anogenital injury in consensual and non-consensual
fisting intercourse: A systematic review.
AB - Fisting is an uncommon and potentially dangerous sexual practice. This is usually
a homosexual activity, but can also be a heterosexual or an autoerotic practice.
A systematic review of the forensic literature yielded 14 published studies from
8 countries between 1968 and 2016 that met the inclusion/exclusion criteria,
illustrating that external anogenital (anal and/or genital) trauma due to fisting
is observed in 22.2% and 88.8% (reported consensual and non-consensual
intercourse, respectively) of the subjects, while internal injuries are observed
in the totality of the patients. Establishing the reliability of the conclusions
of these studies is difficult due to a lack of uniformity in methodology used to
detect and define injuries. Taking this limit into account, the aim of this
article is to give a description of the external and internal injuries subsequent
to reported consensual and non-consensual fisting practice, and try to find a
relation between this sexual practice, the morphology of the injuries, the
correlation with the use of drugs, and the relationship with assailant, where
possible. The findings reported in this paper could be useful, especially when
concerns of sexual assault arise.
PMID- 27614328
TI - Blood pressure and aEEG in the 96h after birth and correlations with
neurodevelopmental outcome in extremely preterm infants.
AB - BACKGROUND: The management of hypotension immediately after the birth of preterm
infants is controversial. AIM: To investigate the relationship between blood
pressure (BP), amplitude-integrated electroencephalography (aEEG), and
neurodevelopmental outcome in extremely preterm infants. METHODS: BP and aEEG
were monitored for 96h after birth in 36 infants born at <27weeks gestation. aEEG
data were analyzed with Burdjalov scores. Correlations of aEEG findings with BP
and several clinical characteristics, including the Score for Neonatal Acute
Physiology, Perinatal Extension-II (SNAPPE-II) were explored. A subgroup analysis
of BP, aEEG activity, and neurodevelopmental outcome at 18-22months corrected age
was also performed. Poor outcome was defined as death or a developmental quotient
<70. RESULTS: Multiple regression analyses revealed no association between BP
during the first 48h after birth and aEEG activity. However, BP 48-96h after
birth was significantly associated with simultaneous aEEG activity (p<0.001).
Within 48h after birth, SNAPPE-II was significantly associated with aEEG
activity. Outcome was assessed in 32 infants; 24 and 8 of whom had good and poor
outcomes, respectively. aEEG activity was significantly lower in neonates with a
poor outcome than those with a good outcome (<0.001). No significant differences
in outcome were observed for BP. CONCLUSION: The activity of aEEG was associated
with illness severity during the first 48h after birth. After 48h, there was no
effect of illness severity but there was an association with BP. We do not know
if hypotension results in a poor outcome. However, aEEG activity was associated
with neurodevelopmental outcome.
PMID- 27614329
TI - Placental histopathology lesions and pregnancy outcome in pregnancies complicated
with symptomatic vs. non-symptomatic placenta previa.
AB - BACKGROUND: The mechanisms involved in bleeding in cases of placenta previa (PP)
and the effect on pregnancy outcome is unclear. OBJECTIVES: We aimed to compare
pregnancy outcome and placental histopathology in pregnancies complicated with
symptomatic (bleeding) vs. non-symptomatic PP, and to study the effects of the co
existence of histopathological retro-placental hemorrhage (RPH) in cases of
symptomatic PP on neonatal and maternal outcomes. STUDY DESIGN: Labor and
maternal characteristics, neonatal outcome and placental histopathology lesions
of pregnancies with PP, delivered between 24 and 42weeks, during 2009-2015, were
reviewed. Results were compared between PP who had elective cesarean delivery
(CD) (previa group) and PP with bleeding necessitating emergent CD (symptomatic
previa group). Placental lesions were classified to lesions consistent with
maternal malperfusion or fetal thrombo-occlusive disease (vascular and villous
changes), and inflammatory lesions. RESULTS: Compared to the previa group (n=63),
the symptomatic previa group (n=74) was characterized by older patients
(p<0.001), higher rate of smokers (p=0.005), thrombophilia (p=0.038), and preterm
deliveries (p<0.001). Placentas within the symptomatic previa group were smaller,
with higher rates of weight<10th% (p=0.02), RPH (p<0.001) and villous changes
related to maternal malperfusion (p=0.023). As compared to symptomatic PP without
RPH, co-existence of RPH was associated with higher rate of adverse neonatal
outcome (p<0.001) and maternal blood transfusion (p=0.02). On multivariate
regression analysis, composite adverse neonatal outcome was found to be dependent
on coexisting RPH (OR=2.8, 95%CI 1.2-11.7, p=0.03), and low gestational age
(OR=3.1, 95%CI 1.6-4.9, p=0.02). CONCLUSIONS: Symptomatic placenta previa is
associated with increased placental malperfusion lesions suggesting an
association of maternal malperfusion with abnormal placental separation. The
coexisting finding of RPH with symptomatic placenta previa can be seen as a
marker for more extensive/severe placental separation, hence the association with
maternal transfusion requirements and poorer fetal outcome.
PMID- 27614330
TI - Mother-child interaction and cognitive development in children prenatally exposed
to methadone or buprenorphine.
AB - OBJECTIVE: To assess the influence of mother-child interaction on children's
cognitive development in a group of children prenatally exposed to methadone or
buprenorphine. STUDY DESIGN: The study is part of a prospective longitudinal
project investigating the development of children born to women in opioid
maintenance therapy (OMT). The sample includes 67 children born between 2005 and
2007, 35 of which prenatally exposed to either methadone or buprenorphine and 32
non-exposed comparison children. RESULTS: Both groups scored within the normal
range of development. However, the OMT group scored significantly lower on
measures of cognitive development and mother-child interaction compared to the
comparison group. Cognitive development was found to be affected by both group
status, F(1,54)=5.65, p=0.02, eta(2)=0.10 and mother-child interaction
F(1,54)=5.26, p=0.03, eta(2)=0.09. Behavioral inhibition (statue), sensorimotor
function (imitating hand positions), and short-term memory (sentences) was
influenced by group status while narrative memory and vocabulary were found to be
more influenced by mother-child interaction. CONCLUSIONS: Different risk factors
may influence different cognitive functions in children of women in OMT.
Specifically, language-related cognitive skills may be more related to mother
child interaction while performance in higher cognitive functions requiring
precise control over sensorimotor responses may be more sensitive to other
factors such as prenatal OMT exposure, genetics, and/or prenatal exposure to
other substances.
PMID- 27614331
TI - Infant temperamental reactivity, maternal and grandparental sensitivity:
Differential susceptibility for behavior problems in China.
AB - BACKGROUND: The differential susceptibility hypothesis suggests that children's
innate characteristics and their rearing experiences interact differentially
during development. Recently, the study of interactions between infants'
temperament and rearing experiences has become a research hotspot. In China,
grandparental care is a very common phenomenon, with many infants taken care of
by grandparents while mothers are out for work. AIM: To investigate whether the
associations between maternal and grandmaternal sensitivity, and behavior
problems were moderated by infant temperamental reactivity, while the infants
were raised by both their mothers and grandmothers. SUBJECTS: A total of 71
infants (average age of 17.6months), their mothers and grandmothers were included
in this study. OUTCOME MEASURES: Maternal sensitivity and grandmaternal
sensitivity were assessed with the Maternal Behavior Q-sort-Chinese Version,
infants' temperamental reactivity was measured with Carey's Toddler Temperament
Questionnaire-Chinese Revision, and infants' behavior problems were measured with
the Infant-Toddler Social and Emotional Assessment-Chinese Version. RESULTS:
Maternal sensitivity significantly predicted infants' impulsivity and aggression.
Infants' temperamental reactivity moderated the effect of maternal sensitivity on
infants' general anxiety. In addition, infant temperamental reactivity moderated
the impact of grandmaternal sensitivity on infants' separation distress.
CONCLUSIONS: Our results support the differential susceptibility hypothesis to
some extent. Infants with high temperamental reactivity not only suffer more from
low maternal and grandmaternal sensitivity, but also benefit more from high
maternal and grandmaternal sensitivity as compared to those infants with low
temperamental reactivity.
PMID- 27614332
TI - Genome-wide identification, evolution of chromobox family genes and their
expression in Nile tilapia.
AB - Chromobox (Cbx) family proteins are transcriptional repressors that involved in
epigenetic and developmental processes. In this study, comprehensive analyses of
Cbxs were performed using available genome databases from representative animal
species. The Cbx family were originated from one Polycomb (Pc) gene like the
yeast Pc, which duplicated into two and gave rise to the Pc and the
Heterochromatin protein 1 (Hp1) identified in invertebrates from protozoon to
lancelet. Rapid expansion of Cbx family members was observed in vertebrates as ~8
(5 Pc and 3 Hp1) were identified in spotted gar, coelacanth and tetrapods.
Further expansion of the members to ~14 (9 Pc and 5 Hp1) was observed in teleosts
due to the third round genome duplication (3R). Based on transcriptome data from
eight adult tilapia tissues, most of the Cbxs were found to be dominantly
expressed in the brain, testis, ovary and heart. Analyses of the gonadal
transcriptome data from four developmental stages revealed that all Cbxs were
expressed in both ovary and testis except Cbx7b, with significant increase of the
total and average RPKM from 5 to 90dah (days after hatching). By in situ
hybridization, the three most highly and sexual dimorphically expressed Cbx genes
in gonads, Cbx1b, Cbx3a and Cbx5, were found to be expressed in phase I and II
oocytes of the ovary, and in secondary spermatocytes (Cbx1b and Cbx3a) and
spermatids (Cbx5) of the testis. Our results revealed the evolution of Cbx genes
and indicated a potential role of Cbxs in epigenetic regulation of gametogenesis.
PMID- 27614333
TI - Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.
AB - PURPOSE: Early salvage radiotherapy following radical prostatectomy for prostate
cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to
determine the optimal definition of early salvage radiotherapy. MATERIALS AND
METHODS: We performed a multi-institutional retrospective study of 657 men who
underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made
to determine the optimal definition of early salvage radiotherapy, including 1)
the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to
21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre
salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to
0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen
deprivation therapy, and biochemical relapse-free, distant metastases-free and
prostate cancer specific survival. RESULTS: Median followup was 9.8 years. Time
from radical prostatectomy to salvage radiotherapy did not correlate with 10-year
biochemical relapse-free survival rates (R2 = 0.18). Increasing pre-salvage
radiotherapy prostate specific antigen strongly correlated with biochemical
relapse-free survival (R2 = 0.91). Increasing detectable pre-salvage radiotherapy
prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than
0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44%
and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%),
distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate
cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On
multivariable analysis early salvage radiotherapy (prostate specific antigen
greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in
biochemical failure, use of salvage androgen deprivation therapy and distant
metastases compared to very early salvage radiotherapy (prostate specific antigen
0.01 to 0.2 ng/ml). CONCLUSIONS: The duration from radical prostatectomy to
salvage radiotherapy is not independently prognostic for outcomes after salvage
radiotherapy and it should not be used to define early salvage radiotherapy.
Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5
ng/ml or less may be inadequate to define early salvage radiotherapy and it has a
relevant impact on ongoing and future clinical trials.
PMID- 27614334
TI - Device Survival after Primary Implantation of an Artificial Urinary Sphincter for
Male Stress Urinary Incontinence.
AB - PURPOSE: The AMS 800TM artificial urinary sphincter remains the gold standard for
the surgical management of male stress urinary incontinence. We reviewed
artificial urinary sphincter device survival after primary implantation.
MATERIALS AND METHODS: Retrospective data were collected from the AMS 800 patient
information form database. Since 1972, 77,512 patient information forms for
primary artificial urinary sphincter implantation have been completed in the
United States. Following exclusion of procedures performed in children and
females, and those labeled with an unknown surgical technique, 27,096 artificial
urinary sphincter cases were included in the analysis. Collected variables
included patient age, surgical approach, number of cuffs and surgeon volume.
Measured outcomes included device explantation, device revision, component
revision and time to each event. RESULTS: Artificial urinary sphincter insertion
was performed by low volume implanters in 22,165 (82.6%) cases. The approach was
perineal in 18,373 cases (67.8%) and a tandem cuff was used in 2,224 cases
(8.2%). Overall 5,723 cases required revision or explantation (21.1%). Younger
age and penoscrotal approach were associated with higher device explantation and
revision rates, while the use of a tandem cuff was associated with higher
explantation rates. On multivariate analysis younger age, penoscrotal approach
and use of a tandem cuff but not surgeon volume were significant factors
associated with device explantation and component revision. CONCLUSIONS: These
data provide a general overview of artificial urinary sphincter device survival
and may serve urologists when counseling patients. Younger age, penoscrotal
approach and use of a tandem cuff may be associated with inferior outcomes.
PMID- 27614335
TI - Correlation between ultrasonic power spectrum and bone density on the heel.
AB - The purposes of this paper were to evaluate the correlation between ultrasonic
power spectrum and bone density and to extract the effectiveness of parameters
from power spectrum for evaluating bone density. A total of 50 persons 24-72years
of age were recruited. All study participants underwent bone mineral density
(BMD) measurements of the lumbar spine (vertebral levels L1-L4). The participants
also underwent calcaneal measurements to determine ultrasonic power spectrum with
central frequencies of 0.5MHz. Three parameters from normalized power spectrum,
called principle frequency (PF), frequency band (FB), and amplitude for principle
frequency (APF), were chosen and be evaluated the correlation with the lumbar
spine BMD. The correlation coefficient of PF, FB and APF with BMD was r=-0.48
(p<0.001), r=0.48 (p<0.001), and r=-0.71 (p<0.001), respectively. The results
showed that the correlation between APF and BMD was better than the correlation
among PF, FB and BMD, and APF have a significant correlation with BMD. In
conclusion, the correlations among the parameters of ultrasonic power spectrum
and BMD are significant, and especially APF performs better than PF and FB in
evaluating bone density of participants. These results suggest that ultrasonic
power spectrum may contain substantial information not already contained in BUA
and SOS. A multiple regression model including all three QUS variables was
somewhat more predictive of BMD than a model including only BUA and SOS.
PMID- 27614336
TI - Increased electroencephalographic activity in crack-cocaine users visualizing
crack cues.
AB - This study aimed to examine electrophysiologically the cerebral function under
visual cue-reactivity paradigm in crack-cocaine users. This was an exploratory
open trial in which young crack-cocaine-users and non-users were clinically
examined. The participants' brain activity was analyzed by an event-related
potentials procedure under a cue-reactivity paradigm with the random visual
presentation of crack-related and neutral images. Nine young male crack-cocaine
users and nine age-matched male healthy subjects from research center's
neighborhood volunteered themselves to participate in this study. We demonstrated
through electrophysiological tools that crack-cocaine users are more likely to
show higher brain activity, notably in the frontal lobe region, when processing
crack-related images. Though imaging studies have already showed increased brain
activity in this paradigm, this data shows that event-related potentials can be
an effective tool for brain evaluation in addiction.
PMID- 27614337
TI - Strangulated transmesosigmoid hernia as a late complication of a fall from a
height: A case report.
AB - INTRODUCTION: A transmesosigmoid hernia is defined as small bowel herniation
through a complete defect involving both layers of the sigmoid mesentery. Blunt
trauma injury to the sigmoid mesocolon has been reported only rarely. We herein
report a case of a strangulated transmesosigmoid hernia associated with a history
of a fall from a height. PRESENTATION OF CASE: A 43-year-old woman presented to
our hospital for evaluation of vomiting. She had no history of abdominal surgery
but had sustained a complete spinal cord injury and pelvic fracture secondary to
a fall from a height 25 years earlier. A computed tomography scan of her abdomen
and pelvis demonstrated a closed loop of small bowel in the pelvis, with a zone
of transition in the left lower abdomen. Although the cause of the obstruction
was difficult to establish, ischemia was strongly suspected; therefore, the
decision was made to perform emergency exploratory laparoscopy. During
laparoscopy, a loop of ileum was observed to have herniated through a full
thickness defect in the sigmoid mesocolon, consistent with a transmesosigmoid
hernia. The herniated loop was strangulated but not gangrenous and was
successfully reduced using laparoscopic graspers. The incarcerated small bowel
appeared viable and was therefore not resected. The defect was closed with a
running suture. The patient had an uneventful postoperative course with no
recurrence. DISCUSSION AND CONCLUSION: Abdominal blunt trauma can cause sigmoid
mesenteric rupture resulting in a transmesosigmoid hernia. In the management of
transmesosigmoid hernias, laparoscopic herniorrhaphy has the advantage of
facilitating simultaneous diagnosis and surgical intervention.
PMID- 27614338
TI - Campylobacter colitis: Rare cause of toxic megacolon.
AB - INTRODUCTION: Campylobacter is the leading cause of bacterial diarrhoeal illness
worldwide. Toxic megacolon is a rare but potentially devastating complication.
PRESENTATION OF CASE: A 55year old female with liver cirrhosis, alcoholism and
hepatitis C, presented with severe colitis and stool specimen positive for
Campylobacter. She developed septic shock, multi-organ dysfunction syndrome and
toxic megacolon unresponsive to medical therapy, and underwent a subtotal
colectomy with end ileostomy. Despite initial improvement, the patient died on
postoperative day 4. DISCUSSION: Early surgical consultation is essential as
toxic megacolon may be complicated by perforation or uncontrolled bleeding;
progressive colonic dilatation with clinical deterioration is also an important
indication for surgery. CONCLUSION: Toxic megacolon should be considered in a
patient with Campylobacter colitis who becomes critically unwell. Despite
treatment, toxic megacolon is associated with a significant risk of mortality.
PMID- 27614340
TI - T2 breast cancer presenting with diffuse liver metastases and hepatic failure
following fertility treatment. Cautionary report.
AB - BACKGROUND: Diffuse hepatic metastases with hepatic failure as a presentation of
a T2 breast cancer is rare. This is also remarkable seeing our case had been on
fertility treatments before presentation. There are no documented reports of
breast cancer patient on fertility treatment presenting with diffuse hepatic
metastases and liver failure. CASE SUMMARY: A 41 year old Para 1 Nigerian woman
being managed for secondary infertility with an extended use of clomiphene
presented with a 3 months history of a left breast lump, nipple bleeding and
later, yellowness of eyes, right hypochondrial pain malaise and drowsiness.
Abdominal USS showed an enlarged liver with diffuse metastatic nodules. Liver
function tests showed persistently elevating liver enzymes and serum bilirubin.
Serology showed Hepatitis B negative. She was diagnosed with a T2 left invasive
ductal carcinoma, Er-, Pr+ Her2+ with deteriorating liver function from diffuse
hepatic metastases She had chemotherapy but succumbed barely a week of
presentation. CONCLUSION: Breast cancer screening for patients before fertility
treatments and continual surveillance while on such treatment is highly
recommended.
PMID- 27614339
TI - Rapid growing pulmonary cavernous lymphangioma after chronic process for ten
years.
AB - INTRODUCTION: Solitary cavernous lymphangioma is very rare disease characterized
by abnormally proliferating lymphatic vessels. We report a 49-year-old woman with
a cavernous pulmonary lymphangioma showing rapid growth after remaining indolent
for 10 years. PRESENTATION OF CASE: Chest computed tomography revealed a
solitary, poorly demarcated mass in the left lower lobe; however, the tumour grew
in size over the next 6 months. A left lower lobectomy was performed following
suspected lung cancer. Histopathological and immunohistochemical analysis of the
resected specimens revealed a pulmonary cavernous lymphangioma. DISCUSSION: It is
difficult to make an accurate diagnosis of solitary cavernous lymphangioma by
imaging findings, therefore a surgical resection is recommended as the diagnostic
and therapeutic modality. CONCLUSION: A pulmonary lymphangioma should be included
in the differential diagnosis of a rapidly growing tumour.
PMID- 27614345
TI - Guidelines, guidelines, guidelines!
PMID- 27614347
TI - Practise observed.
PMID- 27614348
TI - Nanocall: an open source basecaller for Oxford Nanopore sequencing data.
AB - MOTIVATION: The highly portable Oxford Nanopore MinION sequencer has enabled new
applications of genome sequencing directly in the field. However, the MinION
currently relies on a cloud computing platform, Metrichor (metrichor.com), for
translating locally generated sequencing data into basecalls. RESULTS: To allow
offline and private analysis of MinION data, we created Nanocall. Nanocall is the
first freely available, open-source basecaller for Oxford Nanopore sequencing
data and does not require an internet connection. Using R7.3 chemistry, on two
E.coli and two human samples, with natural as well as PCR-amplified DNA, Nanocall
reads have ~68% identity, directly comparable to Metrichor '1D' data. Further,
Nanocall is efficient, processing ~2500 Kbp of sequence per core hour using the
fastest settings, and fully parallelized. Using a 4 core desktop computer,
Nanocall could basecall a MinION sequencing run in real time. Metrichor provides
the ability to integrate the '1D' sequencing of template and complement strands
of a single DNA molecule, and create a '2D' read. Nanocall does not currently
integrate this technology, and addition of this capability will be an important
future development. In summary, Nanocall is the first open-source, freely
available, off-line basecaller for Oxford Nanopore sequencing data. AVAILABILITY
AND IMPLEMENTATION: Nanocall is available at github.com/mateidavid/nanocall,
released under the MIT license. CONTACT: matei.david@oicr.on.caSupplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 27614349
TI - The OGCleaner: filtering false-positive homology clusters.
AB - : Detecting homologous sequences in organisms is an essential step in protein
structure and function prediction, gene annotation and phylogenetic tree
construction. Heuristic methods are often employed for quality control of
putative homology clusters. These heuristics, however, usually only apply to
pairwise sequence comparison and do not examine clusters as a whole. We present
the Orthology Group Cleaner (the OGCleaner), a tool designed for filtering
putative orthology groups as homology or non-homology clusters by considering all
sequences in a cluster. The OGCleaner relies on high-quality orthologous groups
identified in OrthoDB to train machine learning algorithms that are able to
distinguish between true-positive and false-positive homology groups. This
package aims to improve the quality of phylogenetic tree construction especially
in instances of lower-quality transcriptome assemblies. AVAILABILITY AND
IMPLEMENTATION: https://github.com/byucsl/ogcleaner CONTACT:
sfujimoto@gmail.comSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27614350
TI - Assessment of cancer and virus antigens for cross-reactivity in human tissues.
AB - MOTIVATION: Cross-reactivity (CR) or invocation of autoimmune side effects in
various tissues has important safety implications in adoptive immunotherapy
directed against selected antigens. The ability to predict CR (on-target and off
target toxicities) may help in the early selection of safer therapeutically
relevant target antigens. RESULTS: We developed a methodology for the calculation
of quantitative CR for any defined peptide epitope. Using this approach, we
performed assessment of 4 groups of 283 currently known human MHC-class-I
epitopes including differentiation antigens, overexpressed proteins, cancer
testis antigens and mutations displayed by tumor cells. In addition, 89 epitopes
originating from viral sources were investigated. The natural occurrence of these
epitopes in human tissues was assessed based on proteomics abundance data, while
the probability of their presentation by MHC-class-I molecules was modelled by
the method of Kesmir et al. which combines proteasomal cleavage, TAP affinity and
MHC-binding predictions. The results of these analyses for many previously
defined peptides are presented as CR indices and tissue profiles. The methodology
thus allows for quantitative comparisons of epitopes and is suggested to be
suited for the assessment of epitopes of candidate antigens in an early stage of
development of adoptive immunotherapy. AVAILABILITY AND IMPLEMENTATION: Our
method is implemented as a Java program, with curated datasets stored in a MySQL
database. It predicts all naturally possible self-antigens for a given sequence
of a therapeutic antigen (or epitope) and after filtering for predicted
immunogenicity outputs results as an index and profile of CR to the self-antigens
in 22 human tissues. The program is implemented as part of the iCrossR webserver,
which is publicly available at http://webclu.bio.wzw.tum.de/icrossr/ CONTACT:
d.frishman@wzw.tum.deSupplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 27614351
TI - Preanalytical errors in medical laboratories: a review of the available
methodologies of data collection and analysis.
AB - Preanalytical errors have previously been shown to contribute a significant
proportion of errors in laboratory processes and contribute to a number of
patient safety risks. Accreditation against ISO 15189:2012 requires that
laboratory Quality Management Systems consider the impact of preanalytical
processes in areas such as the identification and control of non-conformances,
continual improvement, internal audit and quality indicators. Previous studies
have shown that there is a wide variation in the definition, repertoire and
collection methods for preanalytical quality indicators. The International
Federation of Clinical Chemistry Working Group on Laboratory Errors and Patient
Safety has defined a number of quality indicators for the preanalytical stage,
and the adoption of harmonized definitions will support interlaboratory
comparisons and continual improvement. There are a variety of data collection
methods, including audit, manual recording processes, incident reporting
mechanisms and laboratory information systems. Quality management processes such
as benchmarking, statistical process control, Pareto analysis and failure mode
and effect analysis can be used to review data and should be incorporated into
clinical governance mechanisms. In this paper, The Association for Clinical
Biochemistry and Laboratory Medicine PreAnalytical Specialist Interest Group
review the various data collection methods available. Our recommendation is the
use of the laboratory information management systems as a recording mechanism for
preanalytical errors as this provides the easiest and most standardized mechanism
of data capture.
PMID- 27614352
TI - Measurement of serum 3-epi-25-hydroxyvitamin D3, 25-hydroxyvitamin D3 and 25
hydroxyvitamin D2 in infant, paediatric and adolescent populations of Korea using
ultra-performance liquid chromatography-tandem mass spectrometry.
AB - Background We evaluated the performance of ultra-performance liquid
chromatography-tandem mass spectrometry to measure serum 3-epi-25-hydroxyvitamin
D3, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 concentrations in 519 infant,
paediatric and adolescent serum samples in Korea. Methods We used a Kinetex XB
C18 column and isocratic methanol/water (77.5/22.5, v/v) with 0.025% (v/v) high
performance liquid chromatography solvent additive flowing at 0.25 mL/min,
yielding an 11 min/sample run time. A TQD triple quadrupole mass spectrometer in
electrospray ionization positive ion mode with multiple reaction monitoring
transition via an MSMS vitamin D kit was used to evaluate precision, carryover,
ion suppression and linearity. Samples were prepared using the 4-phenyl-1,2,4
triazoline-3,5-dione derivatization method. Results Intra- and inter-run
precisions were 1.23-13.28% and 1.02-10.08%, respectively. Group carryovers were
0.27% and 0.10%, respectively. There was no ion suppression. The calibration
curve showed good linearity from calibrator Level 1 (11.75 nmol/L) to 6 (375
nmol/L) with R2 > 0.9999. The 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D3
peaks were clearly separated in the extracted ion chromatogram. Infant serum
samples 3-epi-25-hydroxyvitamin D3 concentrations were significantly higher than
paediatric and adolescent concentrations. Conclusions The ultra-performance
liquid chromatography-tandem mass spectrometry assay performed acceptably,
clearly separating 3-epi-25-hydroxyvitamin D3 from 25-hydroxyvitamin D3. High 3
epi-25-hydroxyvitamin D3 concentrations were observed in infant but not in
paediatric and adolescent serum samples.
PMID- 27614353
TI - Lipoprotein-associated phospholipase A2: a new marker to determine cardiovascular
risk in hypercholesterolemic dyslipidaemic children.
AB - Background Inflammation and hypercholesterolaemia contribute to atherosclerotic
changes which can start in childhood. Children with hyperlipidaemias are at high
risk for early coronary atherosclerosis. This study evaluates the relationship
between lipoprotein-associated phospholipase A2 (Lp-PLA2), carotid intima-media
thickness (CIMT) and flow-mediated dilatation in hypercholesterolaemic
dyslipidaemic children. Methods We performed a case-control study consisting of
43 cases, aged 2 to 17 years, and 24 age-matched controls. Fasting blood samples
were obtained from both groups for the measurement of a lipid profile (total
cholesterol, LDL-C, HDL-C and triglycerides) and Lp-PLA2 in mass units. The
latter was determined with a turbidimetric immunoassay method (PlacTest, DiaDexus
Inc.) applied to an automated analyser. CIMT and flow-mediated dilatation
measurements were undertaken by a paediatric cardiologist, using high-resolution
B-mode ultrasonography. Results Total cholesterol, LDL-C and Lp-PLA2
concentrations were significantly higher in the cases than in the controls ( p <
0.001 for all three parameters). While CIMT values were also significantly higher
in the patients compared to the controls ( P = 0.001), flow-mediated dilatation
values were significantly lower ( P = 0.001). We found positive correlations
between Lp-PLA2 and total cholesterol ( r = 0.41, P = 0.001), Lp-PLA2 and LDL-C (
r = 0.36, P = 0.004), Lp-PLA2 and CIMT ( r = 0.44, P = 0.019) and LDL-C and CIMT
( r = 0.41, P = 0.032); there were negative correlations between Lp-PLA2 and flow
mediated dilatation ( r = -0.15, P = 0.045), total cholesterol and flow-mediated
dilatation ( r = -0.45, P = 0.017), LDL-C and flow-mediated dilatation ( r =
0.51, P = 0.006) and CIMT and flow-mediated dilatation ( r = -0.45, P = 0.016).
Conclusion Lp-PLA2 concentrations are significantly elevated in
hypercholesterolaemic dyslipidaemic children. Given the association of Lp-PLA2
with markers of atherosclerosis (total cholesterol, LDL-C, CIMT and flow-mediated
dilatation), the finding of increased concentrations of Lp-PLA2 could be used to
identify early atherosclerotic changes in hypercholesterolaemic dyslipidaemic
children and may inform their clinical management.
PMID- 27614354
TI - Hepatitis C virus core antigen assay: an alternative method for hepatitis C
diagnosis.
AB - Background The study aimed to evaluate a fully automated chemiluminescent
immunoassay and compared it with a quantitative RNA assay and anti-HCV assay to
verify the utility of this automated Ag assay as an alternative method for
hepatitis C diagnosis. Methods A total of 229 serum samples previously tested for
anti-HCV concentrations by the Architect Anti-HCV assay, were selected for HCV
RNA testing by real time RT-PCR kit (Shanghai ZJ Bio-Tec Co., Ltd) and 125
specimens were tested for HCV Ag by the Architect HCV core Antigen kit. Results
The log10 HCVAg and HCV RNA concentrations were highly correlated [ r = 0.834);
with HCV RNA as the comparator test, HCVAg had 100% specificity, 100% positive
predictive value (PPV) and 94.8% sensitivity. We found 1 pg/mL of total HCV core
Ag is equivalent to approximately 6607HCV RNA international units (IU)/mL.
Receiver operator characteristic curve analysis showed that the area under the
curve of HCV core Ag (0.989) was greater than HCV Ab (0.871). HCV Ag
concentrations and RNA-to-Ag ratio of the groups for HCV RNA concentrations <=105
and >105 IU/mL were both significantly different from each other ( P < 0.05).
Conclusion The Architect HCV core Ag assay may be an alternative method for
hepatitis C diagnosis, performed on the same analytical platform and sample as
the anti-HCV assay, shortening the diagnostic window period, demonstrating good
correlation with HCV RNA assay with high specificity and positive predictive
value.
PMID- 27614356
TI - Correlation between chromosomal distribution and embryonic findings on ultrasound
in early pregnancy loss after IVF-embryo transfer.
AB - STUDY QUESTION: Do early pregnancy losses (EPLs) with and without embryos differ
in chromosomal distributions? SUMMARY ANSWER: The chromosomal abnormality rate is
significantly higher in miscarriages with embryos than without after in vitro
fertilization (IVF)-embryo transfer. WHAT IS KNOWN ALREADY: Chromosomal
abnormalities are the main causes of EPLs, the rate of which is up to 24-30% in
the IVF population. Little research has been conducted on the correlations
between the chromosomal distributions of EPL and the existence of an embryo or
with the postmortem embryonic pole length, and the existing results have been
inconsistent. STUDY DESIGN, SIZE, DURATION: The data of 2172 women who underwent
dilation and curettage (D&C) from January 2008 to December 2013 for missed
abortion were analyzed retrospectively. The existence of an embryonic pole and
the length of the postmortem embryonic pole of the EPL were evaluated by
transvaginal sonography (TVS). Ultrasound findings were compared with karyotype
results. PARTICIPANTS/MATERIALS, SETTING, METHOD: This analysis included 2172
infertility patients who had singleton pregnancies and experienced EPLs after IVF
embryo transfer. The EPLs were divided into embryonic and anembryonic groups
based on TVS diagnosis. The crown-rump length of the fetal pole (observed once)
was measured twice for each fetus after confirmation of fetal death, subject to
the final measurement before D&C. The karyotype analysis was performed using
comparative genomic hybridization (CGH) plus fluorescence in situ hybridization
technology. MAIN RESULTS AND THE ROLE OF CHANCE: The chromosomal abnormality rate
was significantly higher in male miscarriages with an embryo than in those
without an embryo (54.14% versus 37.50%, P <= 0.001). In the anembryonic group,
the abnormal karyotype rate was significantly higher in the yolk sac only than
that in the empty sac group (46.11% versus 29.77%, P = 0.001); in the embryonic
group, the abnormal karyotype rate in miscarriages with postmortem embryonic pole
length >20 mm was significantly lower than that in miscarriages with pole length
<10 mm (P = 0.006) and 10-20 mm (P = 0.036). There were significant differences
in abnormal karyotype rates among miscarriages of different developmental stages
(P <= 0.001). The cases with embryonic stages had the highest risk (54.89%) of an
abnormal karyotype and those with fetal stages had the lowest risk (18.18%).
There were significant differences in the length of postmortem embryonic poles
among groups with different karyotypes (P <= 0.001). In addition, trisomy 21,
monosomy X and triploidy had the longest lengths of postmortem embryonic poles
(16, 15.3 and 11.6 mm, respectively). LIMITATIONS, REASONS FOR CAUTION: Although
the efficacy of a non-parametric test is less than that of a parametric test, non
parametric testing was used to compare the embryonic pole lengths in this study,
owing to the non-normal distribution and non-homogeneous variances caused by
limited cases of some rare chromosomal abnormalities. Another limitation was that
CGH was unable to detect mosaicism. Furthermore, the results were not compared
with a non-IVF population. Finally, maternal cell contamination is a major
problem in studying miscarriage tissue, even using molecular techniques. WIDER
IMPLICATIONS OF THE FINDINGS: Although TVS findings clearly cannot replace
karyotype information, our results are important because they call attention to
the fact that EPLs that occur after implantation but prior to embryo formation
frequently have normal karyotypes. This finding might direct future research
towards studies of DNA sequences, or of epigenetic correlations with pregnancy
failure. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the
Scientific Research Foundation of Reproductive and Genetic Hospital of Citic
Xiangya. The authors have declared that no conflicts of interest exist. TRIAL
REGISTRATION NUMBER: N/A.
PMID- 27614355
TI - Length of FMR1 repeat alleles within the normal range does not substantially
affect the risk of early menopause.
AB - STUDY QUESTION: Is the length of FMR1 repeat alleles within the normal range
associated with the risk of early menopause? SUMMARY ANSWER: The length of repeat
alleles within the normal range does not substantially affect risk of early
menopause. WHAT IS KNOWN ALREADY: There is a strong, well-established
relationship between length of premutation FMR1 alleles and age at menopause,
suggesting that this relationship could continue into the normal range. Within
the normal range, there is conflicting evidence; differences in ovarian reserve
have been identified with FMR1 repeat allele length, but a recent population
based study did not find any association with age at menopause as a quantitative
trait. STUDY DESIGN, SIZE, DURATION: We analysed cross-sectional baseline survey
data collected at recruitment from 2004 to 2010 from a population-based,
prospective epidemiological cohort study of >110 000 women to investigate whether
repeat allele length was associated with early menopause. PARTICIPANTS/MATERIALS,
SETTING, METHOD: We included 4333 women from the Breakthrough Generations Study
(BGS), of whom 2118 were early menopause cases (menopause under 46 years) and
2215 were controls. We analysed the relationship between length of FMR1 alleles
and early menopause using logistic regression with allele length as continuous
and categorical variables. We also conducted analyses with the outcome age at
menopause as a quantitative trait as well as appropriate sensitivity and
exploratory analyses. MAIN RESULTS AND THE ROLE OF CHANCE: There was no
association of the shorter or longer FMR1 allele or their combined genotype with
the clinically relevant end point of early menopause in our main analysis.
Likewise, there were no associations with age at menopause as a quantitative
trait in our secondary analysis. LIMITATIONS, REASONS FOR CAUTION: Women with
homozygous alleles in the normal range may have undetected FMR1 premutation
alleles, although there was no evidence to suggest this. We estimate minor
dilution of risk of early menopause from the likely inclusion of some women with
menopause at over 45 years in the early menopause cases due to age-rounding bias
in self-reports. WIDER IMPLICATIONS OF THE FINDINGS: There is no robust evidence
in this large study that variation within the normal range of FMR1 repeat alleles
influences timing of menopause in the general population, which contradicts
findings from some earlier, mainly smaller studies. The FMR1 CGG repeat
polymorphism in the normal range is unlikely to contribute to genetic
susceptibility to early menopause. STUDY FUNDING/COMPETING INTERESTS: We thank
Breast Cancer Now and The Institute of Cancer Research for funding the BGS. The
Institute of Cancer Research acknowledges NHS funding to the NIHR Biomedical
Research Centre. The study was funded by the Wellcome Trust (grant number
085943). There are no competing interests. TRIAL REGISTRATION NUMBER: Not
applicable.
PMID- 27614357
TI - A magic red coat on the surface of young leaves: anthocyanins distributed in
trichome layer protect Castanopsis fissa leaves from photoinhibition.
AB - The presence of anthocyanins in young leaves plays an important role in
mitigation against photodamage and allows leaves to grow and develop normally.
Many studies have reported that foliar anthocyanins are distributed within the
vacuoles of mesophyll cells, so we explored the novel defence style of
anthocyanin-coated young leaves of Castanopsis fissa, a dominant subtropical
forest tree species, via removable trichomes. Anthocyanins were distributed in C.
fissa leaf trichomes, which produced a red coating for the young leaves. As young
leaves developed and then matured, the thickness and density of the anthocyanin
trichomes progressively decreased, the coating finally disappearing, allowing
greater utilization of light by mature leaves. In addition to anthocyanins, the
trichomes contained a remarkably high amount of phenolics, which enable the red
coating to be more efficient in screening ultraviolet light. Compared with mature
leaves, the young leaves exhibited lower photosynthetic ability, which was
attributable to the reduced chlorophyll and Rubisco contents. Removal of the red
coating had little effect on the photosynthetic capacity of young leaves.
However, the young leaves without the coating suffered greater light-induced
photoinhibition due to greater excess light entering the chloroplast and the
production of H2O2 Our results suggest that the anthocyanin coating is
photoprotective and this anthocyanin defence style may be a metabolically cost
effective way of adjusting the anthocyanin content in response to demand.
PMID- 27614358
TI - First insights into the functional role of vasicentric tracheids and parenchyma
in eucalyptus species with solitary vessels: do they contribute to xylem
efficiency or safety?
AB - The relationship between hydraulic specific conductivity (ks) and vulnerability
to cavitation (VC) with size and number of vessels has been studied in many
angiosperms. However, few of the studies link other cell types (vasicentric
tracheids (VT), fibre-tracheids, parenchyma) with these hydraulic functions.
Eucalyptus is one of the most important genera in forestry worldwide. It exhibits
a complex wood anatomy, with solitary vessels surrounded by VT and parenchyma,
which could serve as a good model to investigate the functional role of the
different cell types in xylem functioning. Wood anatomy (several traits of
vessels, VT, fibres and parenchyma) in conjunction with maximum ks and VC was
studied in adult trees of commercial species with medium-to-high wood density
(Eucalyptus globulus Labill., Eucalyptus viminalis Labill. and Eucalyptus
camaldulensis Dehnh.). Traits of cells accompanying vessels presented
correlations with functional variables suggesting that they contribute to both
increasing connectivity between adjacent vessels-and, therefore, to xylem
conduction efficiency-and decreasing the probability of embolism propagation into
the tissue, i.e., xylem safety. All three species presented moderate-to-high
resistance to cavitation (mean P50 values = -2.4 to -4.2 MPa) with no general
trade-off between efficiency and safety at the interspecific level. The results
in these species do not support some well-established hypotheses of the
functional meaning of wood anatomy.
PMID- 27614359
TI - Winter drought impairs xylem phenology, anatomy and growth in Mediterranean Scots
pine forests.
AB - Continental Mediterranean forests face drought but also cold spells and both
climate extremes can impair the resilience capacity of these forests. Climate
warming could amplify the negative effects of cold spells by inducing premature
dehardening. Here we capitalize on a winter drought-induced dieback triggered by
a cold spell which occurred in December 2001 affecting Scots pine forests in
eastern Spain. We assessed post-dieback recovery by quantifying and comparing
radial growth and xylem anatomy of non-declining (ND, crown cover >50%) and
declining (D, crown cover <=50%) trees in two sites (VP, Villarroya de los
Pinares; TO, Torrijas). We also characterized xylogenesis in both sites and
aboveground productivity in site VP. Dieback caused legacy effects since needle
loss, a 60% reduction in litter fall and radial-growth decline characterized D
trees 3 years after dieback symptoms started appearing in spring 2002. D-trees
formed collapsed tracheids in the 2002-ring, particularly in the most affected VP
site where xylogenesis differences between ND and D trees were most noticeable.
The lower growth rates of D-trees were caused by a shorter duration of their
major xylogenesis phases. In site VP the radial-enlargement and wall-thickening
of tracheids were significantly reduced in D-trees as compared to ND-trees
because these xylogenesis phases tended to start earlier and end later in ND
trees. Gompertz models fitted to tracheid production predicted that maximum
growth rates occurred 11-12 days earlier in ND than in D-trees. The formation of
radially-enlarging tracheids was enhanced by longer days in both study sites and
also by wetter conditions in the driest TO site, but xylogenesis sensitivity to
climate was reduced in D-trees. Winter-drought dieback impairs xylem anatomy and
phenology, aboveground productivity, xylogenesis and growth in Mediterranean
Scots pine populations. Affected stands show a costly post-dieback recovery
challenging their resilience ability.
PMID- 27614361
TI - Reply: The impact of thyroid autoimmunity on IVF/ICSI outcome: re-evaluation of
the findings.
PMID- 27614360
TI - Limited acclimation in leaf anatomy to experimental drought in tropical
rainforest trees.
AB - Dry periods are predicted to become more frequent and severe in the future in
some parts of the tropics, including Amazonia, potentially causing reduced
productivity, higher tree mortality and increased emissions of stored carbon.
Using a long-term (12 year) through-fall exclusion (TFE) experiment in the
tropics, we test the hypothesis that trees produce leaves adapted to cope with
higher levels of water stress, by examining the following leaf characteristics:
area, thickness, leaf mass per area, vein density, stomatal density, the
thickness of palisade mesophyll, spongy mesophyll and both of the epidermal
layers, internal cavity volume and the average cell sizes of the palisade and
spongy mesophyll. We also test whether differences in leaf anatomy are consistent
with observed differential drought-induced mortality responses among taxa, and
look for relationships between leaf anatomy, and leaf water relations and gas
exchange parameters. Our data show that trees do not produce leaves that are more
xeromorphic in response to 12 years of soil moisture deficit. However, the
drought treatment did result in increases in the thickness of the adaxial
epidermis (TFE: 20.5 +/- 1.5 um, control: 16.7 +/- 1.0 um) and the internal
cavity volume (TFE: 2.43 +/- 0.50 mm3 cm-2, control: 1.77 +/- 0.30 mm3 cm-2). No
consistent differences were detected between drought-resistant and drought
sensitive taxa, although interactions occurred between drought-sensitivity status
and drought treatment for the palisade mesophyll thickness (P = 0.034) and the
cavity volume of the leaves (P = 0.025). The limited response to water deficit
probably reflects a tight co-ordination between leaf morphology, water relations
and photosynthetic properties. This suggests that there is little plasticity in
these aspects of plant anatomy in these taxa, and that phenotypic plasticity in
leaf traits may not facilitate the acclimation of Amazonian trees to the
predicted future reductions in dry season water availability.
PMID- 27614362
TI - Endogenous, very small embryonic-like stem cells: critical review, therapeutic
potential and a look ahead.
AB - BACKGROUND: Both pluripotent very small embryonic-like stem cells (VSELs) and
induced pluripotent stem (iPS) cells were reported in 2006. In 2012, a Nobel
Prize was awarded for iPS technology whereas even today the very existence of
VSELs is not well accepted. The underlying reason is that VSELs exist in low
numbers, remain dormant under homeostatic conditions, are very small in size and
do not pellet down at 250-280g. The VSELs maintain life-long tissue homeostasis,
serve as a backup pool for adult stem cells and are mobilized under stress
conditions. An imbalance in VSELs function (uncontrolled proliferation) may
result in cancer. SEARCH METHODS: The electronic database 'Medline/Pubmed' was
systematically searched with the subject heading term 'very small embryonic-like
stem cells'. OBJECTIVE AND RATIONALE: The most primitive stem cells that undergo
asymmetric cell divisions to self-renew and give rise to progenitors still remain
elusive in the hematopoietic system and testes, while the presence of stem cells
in ovary is still being debated. We propose to review the available literature on
VSELs, the methods of their isolation and characterization, their ontogeny, how
they compare with embryonic stem (ES) cells, primordial germ cells (PGCs) and iPS
cells, and their role in maintaining tissue homeostasis. The review includes a
look ahead on how VSELs will result in paradigm shifts in basic reproductive
biology. OUTCOMES: Adult tissue-specific stem cells including hematopoietic,
spermatogonial, ovarian and mesenchymal stem cells have good proliferation
potential and are indeed committed progenitors (with cytoplasmic OCT-4), which
arise by asymmetric cell divisions of pluripotent VSELs (with nuclear OCT-4).
VSELs are the most primitive stem cells and postulated to be an overlapping
population with the PGCs. Rather than migrating only to the gonads, PGCs migrate
and survive in various adult body organs throughout life as VSELs. VSELs express
both pluripotent and PGC-specific markers and are epigenetically and
developmentally more mature compared with ES cells obtained from the inner cell
mass of a blastocyst-stage embryo. As a result, VSELs readily differentiate into
three embryonic germ layers and spontaneously give rise to both sperm and oocytes
in vitro. Like PGCs, VSELs do not divide readily in culture, nor produce teratoma
or integrate in the developing embryo. But this property of being relatively
quiescent allows endogenous VSELs to survive various kinds of toxic insults.
VSELs that survive oncotherapy can be targeted to induce endogenous regeneration
of non-functional gonads. Transplanting healthy niche (mesenchymal) cells have
resulted in improved gonadal function and live births. WIDER IMPLICATIONS: Being
quiescent, VSELs possibly do not accumulate genomic (nuclear or mitochondrial)
mutations and thus may be ideal endogenous, pluripotent stem cell candidates for
regenerative and reproductive medicine. The presence of VSELs in adult gonads and
the fact that they survive oncotherapy may obviate the need to bank gonadal
tissue for fertility preservation prior to oncotherapy. VSELs and their ability
to undergo spermatogenesis/neo-oogenesis in the presence of a healthy niche will
help identify newer strategies toward fertility restoration in cancer survivors,
delaying menopause and also enabling aged mothers to have better quality eggs.
PMID- 27614363
TI - Concept mapping as a method to enhance evidence-based public health.
AB - In this paper we explore the suitability of concept mapping as a method for
integrating knowledge from science, practice, and policy. In earlier research we
described and analysed five cases of concept mapping procedures in the
Netherlands, serving different purposes and fields in public health. In the
current paper, seven new concept mapping studies of co-produced work are added to
extend this analysis. For each of these twelve studies we analysed: (1) how the
method was able to integrate knowledge from practice with scientific knowledge by
facilitating dialogue and collaboration between different stakeholders in the
field of public health, such as academic researchers, practitioners, policy
makers and the public; (2) how the method was able to bring theory development a
step further (scientific relevance); and (3) how the method was able to act as a
sound basis for practical decision-making (practical relevance). Based on the
answers to these research questions, all but one study was considered useful for
building more evidence-based public health, even though the extent to which they
underpinned actual decision-making varied. The chance of actually being
implemented in practice seems strongly related to the extent to which the
responsible decision-makers are involved in the way the concept map is prepared
and executed.
PMID- 27614364
TI - An overview of concept mapping in Dutch mental health care.
AB - About 25 years ago, concept mapping was introduced in the Netherlands and applied
in different fields. A collection of concept mapping projects conducted in the
Netherlands was identified, in part in the archive of the Netherlands Institute
of Mental Health and Addiction (Trimbos Institute). Some of the 90 identified
projects are internationally published. The 90 concept mapping projects reflect
the changes in mental health care and can be grouped into 5-year periods and into
five typologies. The studies range from conceptualizing the problems of the
homeless to the specification of quality indicators for treatment programs for
patients with cystic fibrosis. The number of concept mapping projects has varied
over time. Growth has been considerable in the last 5 years compared to the
previous 5 years. Three case studies are described in detail with 12
characteristics and graphical representations. Concept mapping aligns well with
the typical Dutch approach of the "Poldermodel." A broad introduction of concept
mapping in European countries in cooperation with other countries, such as the
United States and Canada, would strengthen the empirical basis for applying this
approach in health care policy, quality, and clinical work.
PMID- 27614365
TI - Correction Factors for CT Coronary Artery Calcium Scoring Using Advanced Modeled
Iterative Reconstruction Instead of Filtered Back Projection.
AB - RATIONALE AND OBJECTIVES: Iterative reconstruction (IR) computed tomography (CT)
techniques allow for radiation dose reduction while maintaining image quality.
However, CT coronary artery calcium (CAC) scores may be influenced by certain IR
algorithms. The aim of our study is to identify suitable correction factors to
ensure consistency between IR and filtered back projection (FBP)-based CAC
scoring. MATERIAL AND METHODS: A phantom study was performed to derive suitable
correction factors for CAC scores and volume (VOL) values with advanced modeled
iterative reconstruction (or ADMIRE) strength level 3 (ADM3) and 5 (ADM5) vs FBP.
CT data from 40 patients were retrospectively analyzed, and CAC score and VOL
values were obtained following reconstruction with FBP, ADM3, and ADM5. Linear
regression analysis was performed to obtain correction factors. Results with and
without application of the correction factors were compared. Inter-reader
agreement for risk class stratification was analyzed. RESULTS: Phantom
experiments determined a correction factor of 1.14 for ADM3 and 1.25 for ADM5.
FBP-based CAC scores (897 +/- 1413) were significantly higher than uncorrected
scores with ADM3 (746 +/- 1184, P <= .001) and ADM5 (640 +/- 1036, P <= .001).
After application of correction factors, no significant differences were found
for CAC scores based on FBP (897 +/- 1413) and ADM3 (853 +/- 1353, P = .07). The
inter-reader agreement for risk stratification was excellent (k = 0.91).
CONCLUSION: ADM3 can be applied to CAC scoring with use of a correction factor.
When applying a correction factor of 1.14, excellent agreement with standard FBP
for both CAC score and VOL can be achieved.
PMID- 27614366
TI - Reduced burden of childhood diarrheal diseases through increased access to water
and sanitation in India: A modeling analysis.
AB - Each year, more than 300,000 children in India under the age of five years die
from diarrheal diseases. Clean piped water and improved sanitation are known to
be effective in reducing the mortality and morbidity burden of diarrhea but are
not yet available to close to half of the Indian population. In this paper, we
estimate the health benefits (reduced cases of diarrheal incidence and deaths
averted) and economic benefits (measured by out-of-pocket treatment expenditure
averted and value of insurance gained) of scaling up the coverage of piped water
and improved sanitation among Indian households to a near-universal 95% level. We
use IndiaSim, a previously validated, agent-based microsimulation platform to
model disease progression and individual demographic and healthcare-seeking
behavior in India, and use an iterative, stochastic procedure to simulate health
and economic outcomes over time. We find that scaling up access to piped water
and improved sanitation could avert 43,352 (95% uncertainty range [UR] 42,201
44,504) diarrheal episodes and 68 (95% UR 62-74) diarrheal deaths per 100,000
under-5 children per year, compared with the baseline. We estimate a saving of
(in 2013 US$) $357,788 (95% $345,509-$370,067) in out-of-pocket diarrhea
treatment expenditure, and $1646 (95% UR $1603-$1689) in incremental value of
insurance per 100,000 under-5 children per year over baseline. The health and
financial benefits are highly progressive, i.e. they reach poorer households
more. Thus, scaling up access to piped water and improved sanitation can lead to
large and equitable reductions in the burden of childhood diarrheal diseases in
India.
PMID- 27614367
TI - Venous thromboembolism prophylaxis in ED observation units-Is it time?
PMID- 27614368
TI - Usefulness of the thrombolysis in myocardial infarction risk index in acute heart
failure: a pilot study.
AB - BACKGROUND: Risk stratification in acute heart failure (AHF) is vital for both
physicians and paramedical personals. Thrombolysis in myocardial infarction
(TIMI) risk index (TRI) and modified TRI (mTRI) are novel and simple predictive
risk indices that have been examined in patients with acute coronary syndrome.
OBJECTIVE: In the current study, we evaluated the relationship among TRI, mTRI,
and mortality in patients with AHF. METHODS: A total of 293 patients with AHF
were retrospectively analyzed. The patients were divided into 2 groups: group 1
consisted of patients who survived and group 2 consisted of patients who died
during a follow-up period of 120 days. Multivariate hierarchical logistic
regression analysis was performed to evaluate the relationship among TRI, mTRI,
and mortality. RESULTS: All causes of death occurred in 84 patients (28.6%).
Thrombolysis in myocardial infarction risk index was significantly higher in
patients who died during follow-up (20.2 +/- 12.4 vs 14.8 +/- 8.9). The new risk
score showed good predictive value for 120-day mortality. Before laboratory
analysis, in-multivariate hierarchical logistic regression analysis TRI remained
as an independent risk factor for mortality (odds ratio, 2.56; P < .001). After
the laboratory analysis, despite the fact that TRI has lost its predictive value,
mTRI remained an independent risk factor for mortality (odds ratio, 2.08; P =
.01). CONCLUSION: The TRI is a simple and strong predictor of all-cause mortality
in patients who were admitted with AHF. The current study reveals for the first
time the strong predictive value of TRI in patients with AHF.
PMID- 27614369
TI - Euglycemic diabetic ketoacidosis in type 2 diabetes with sodium glucose
cotransporter 2 inhibitors.
PMID- 27614370
TI - The prognostic importance of thiol/disulfide homeostasis in patients with acute
pulmonary thromboembolism.
AB - OBJECTIVE: The aim of this study was to evaluate the role of thiol/disulfide
homeostasis in acute pulmonary embolism (APE) and investigate its compliance to
show hospital mortality of patients with APE. MATERIAL AND METHODS: A total of
173 participants including 113 patients with APE, and 60 healthy individuals were
included in the study. APE group was categorized into two subgroups according to
Pulmonary Embolism Severity Index (PESI) clinic risk score (PESI low group [n=71,
class 1-3] and PESI high group [n=42, class 4-5]). RESULTS: Mean level of native
thiol was lower and disulfide level and disulfide/total thiol ratio were higher
in APE group than control group. In APE group, 14 patients died during
hospitalization. Native thiol and disulfide level, presence of shock, heart rate,
oxygen saturation, right ventricular dysfunction, N-terminal pro-brain
natriuretic peptide, and creatinine levels were found to have prognostic
significance in univariate analysis. On multilvariable logistic regression
analysis, native thiol and disulfide level (odds ratio [OR], 1.16(0.87-1.36);
P=.010 and OR, 1.49; P=.015, respectively), presence of shock (OR, 1.04; P=.012)
and N-terminal pro-brain natriuretic peptide (OR, 1.67; P=.002) were strong
predictors for APE-related hospital mortality after the adjustment of other
potential confounders. CONCLUSION: We have shown that thiol/disulfide homeostasis
can be altered during APE and associated with worse hemodynamic parameters, and
may be used as a prognostic marker for hospital mortality.
PMID- 27614371
TI - Postischemic conditioning does not reduce muscle injury after tourniquet-induced
ischemia-reperfusion injury in rats.
AB - BACKGROUND: The widespread application of tourniquets has reduced battlefield
mortality related to extremity exsanguinations. Tourniquet-induced ischemia
reperfusion injury (I/R) can contribute to muscle loss. Postischemic conditioning
(PostC) confers protection against I/R in cardiac muscle and skeletal muscle
flaps. The objective of this study was to determine the effect of PostC on
extremity muscle viability in an established rat hindlimb tourniquet model.
METHODS: Rats were randomly assigned to PostC-1, PostC-2, or no conditioning
ischemic groups (n = 10 per group). Postischemic conditioning, performed
immediately after tourniquet release, consisted of four 15-second cycles (PostC
1) or eight 15-second cycles (PostC-2) of alternating occlusion and perfusion of
hindlimbs. Twenty-four hours later, muscles were excised. The primary end points
were muscle edema and viability; secondary end points were histologic and markers
of oxidative stress. RESULTS: Ischemia-reperfusion injury decreased viability in
all tourniquet limbs, but viability was not improved in either PostC group.
Likewise, I/R resulted in substantial muscle edema that was not reduced by PostC.
The predominant histologic feature was necrosis, but no significant differences
were found among groups. Markers of oxidative stress were increased similarly
among groups after I/R, although myeloperoxidase activity was significantly
increased only in the no conditioning ischemic group. A protective effect from
PostC was not observed in our model suggesting that PostC was not effective in
reducing I/R skeletal muscle injury or any benefits of PostC were not sustained
for 24 hours when tissues were assessed. CONCLUSION: These negative findings are
pertinent as the military investigates different strategies to extend the safe
time for tourniquet application.
PMID- 27614372
TI - Comprehensive interpretation of hyperglycemia and hyperosmolality on the clinical
outcomes among ischemic stroke patients.
AB - BACKGROUND: Hyperglycemia and hyperosmolality are associated with poor outcomes
among acute ischemic stroke (AIS) patients. OBJECTIVES: We evaluated the
association between hyperglycemia and hyperosmolality, as a combination measure,
with poor outcome among AIS patients. METHODS: We conducted a retrospective study
of AIS patients admitted to the study hospital emergency department between
January and December 2014. Hyperglycemia was defined as serum glucose >144 mg/dL,
and hyperosmolality was defined as a serum osmolality >295 mOsm/kg. After
excluding hypoglycemia and hypoosmolality, the enrolled patients were classified
into the following 4 subgroups: normoglycemia-normoosmolality, hyperglycemia
normoosmolality (HGNO), normoglycemia-hyperosmolality (NGHO), and hyperglycemia
normoosmolality (HGHO). The primary outcome was poor neurological status at 6
months, which was defined as a modified Rankin scale score >=2. RESULTS: Six
hundred seven patients were included. The primary outcome was 336 (55.4%), and it
was highest in the HGNO group (69.6%, 103/148), followed by the HGHO group
(67.9%, 53/78), the NGHO group (57.3%, 43/75) and the normoglycemia
normoosmolality group (44.7%, 137/306). The multivariable logistic regression
analysis revealed that HGNO and HGHO remained significant factors, with primary
outcomes (adjusted odds ratio, 2.08; 95% confidence interval, 1.16-3.71) and 2.93
(1.45-5.91), respectively), whereas NGHO was not a significant factor. Cases of
extremely high sodium levels were few in the NGHO and HGHO groups, whereas
considerable cases of extremely high glucose level were observed in the HGHO
group. CONCLUSION: Hyperglycemia was associated with poor outcome, even after
excluding the effect of hyperosmolality. However, hyperosmolality without
hyperglycemia was not associated with poor outcome. An additive effect, likely
reflecting severe hyperglycemia, was observed.
PMID- 27614373
TI - Does practice make perfect? Prospectively comparing effects of 2 amounts of
practice on tourniquet use performance.
AB - INTRODUCTION: Although a lifesaving skill, currently, there is no consensus for
the required amount of practice in tourniquet use. We compared the effect of 2
amounts of practice on performance of tourniquet use by nonmedical personnel.
METHODS: Israeli military recruits without previous medical training underwent
their standard tactical first aid course, and their initial performance in use of
the Combat Application Tourniquet (CAT; Composite Resources, Rock Hill, SC) was
assessed. The educational intervention was to allocate the participants into a
monthly tourniquet practice program: either a single-application practice (SAP)
group or a triple-application practice (TAP) group. Each group practiced
according to its program. After 3 months, the participants' tourniquet use
performance was reassessed. Assessments were conducted using the HapMed Leg
Tourniquet Trainer (CHI Systems, Fort Washington, PA), a mannequin which measures
time and pressure. RESULTS: A total of 151 participants dropped out, leaving 87
in the TAP group and 69 in the SAP group. On initial assessment, the TAP group
and the SAP group performed similarly. Both groups improved their performance
from the initial to the final assessment. The TAP group improved more than the
SAP group in mean application time (faster by 18 vs 8 seconds, respectively; P =
.023) and in reducing the proportion of participants who were unable to apply any
pressure to the mannequin (less by 18% vs 8%, respectively; P = .009).
CONCLUSION: Three applications per monthly practice session were superior to one.
This is the first prospective validation of a tourniquet practice program based
on objective measurements.
PMID- 27614374
TI - Utilization of a gum elastic bougie to facilitate single lung intubation.
AB - INTRODUCTION: Patients with severe pulmonary hemorrhage due to unilateral trauma
or a bleeding cancer often present to the emergency department in acute
respiratory distress. Although it is generally recommended to perform single lung
intubation, most emergency department providers do not have access to or are not
familiar with double-lumen endotracheal tubes, and blind insertion of an
endotracheal tube to maximum depth does not ensure that the proper
(nonhemorrhagic) lung is ventilated. Therefore, single lung intubation may be
significantly delayed in these patients. The purpose of this study was to assess
the accuracy of using a gum elastic bougie ("bougie") to facilitate single lung
intubation. METHODS: We conducted a prospective, randomized, blinded pilot study
assessing the accuracy of bougie-guided single lung intubation in a fresh human
cadaveric model. Two investigators each inserted a bougie under video
laryngoscope guidance. After passing the vocal cords, the intubator would be
randomized to turn the bougie 90 degrees clockwise (for right mainstem
intubation) or 90 degrees counterclockwise (for left mainstem intubation). The
bougie was then advanced until resistance was met, and the endotracheal tube was
subsequently advanced over the bougie. After intubation, a board-certified
pulmonologist investigator who was blinded to the initial lung selection used a
fiberoptic bronchoscope to confirm placement by assessing endotracheal tube
location with respect to the carina. The primary outcome was the accuracy of
correct lung placement. RESULTS: Two providers performed a total of 45
placements. There were 22 right mainstem and 23 left mainstem intubations. The
overall accuracy was 100% (95% confidence interval, 90.2%-100%) for both right
and left mainstem intubations. DISCUSSION: In our cadaveric model of mainstem
intubation, bougie-guided single lung intubation was highly accurate for both
left and right mainstem intubations. Future studies should assess the accuracy of
this technique among different providers and bodies, as well as live patients.
PMID- 27614375
TI - The cognitive foundations of early arithmetic skills: It is counting and number
judgment, but not finger gnosis, that count.
AB - Following on from ideas developed by Gerstmann, a body of work has suggested that
impairments in finger gnosis may be causally related to children's difficulties
in learning arithmetic. We report a study with a large sample of typically
developing children (N=197) in which we assessed finger gnosis and arithmetic
along with a range of other relevant cognitive predictors of arithmetic skills
(vocabulary, counting, and symbolic and nonsymbolic magnitude judgments).
Contrary to some earlier claims, we found no meaningful association between
finger gnosis and arithmetic skills. Counting and symbolic magnitude comparison
were, however, powerful predictors of arithmetic skills, replicating a number of
earlier findings. Our findings seriously question theories that posit either a
simple association or a causal connection between finger gnosis and the
development of arithmetic skills.
PMID- 27614376
TI - Oxygen therapy in COPD patients with isolated nocturnal hypoxemia; comparison of
quality of life and sleep between bronchitis and emphysema phenotype: A
prospective observational study.
AB - BACKGROUND: COPD is a heterogeneous disease composed by two main phenotypes:
bronchitis (COPDb) and emphysema (COPDe) with different clinical presentation,
physiology, imaging, response to therapy and decline in lung function. The aim of
this study is to evaluate whether nocturnal hypoxemic COPDb and COPDe have a
different behaviour during sleep and the effect of nocturnal oxygen
supplementation (nO2LT). MATERIALS AND METHODS: 75 COPDb and 120 COPDe were
enrolled. All patients performed polysomnography, Pittsburgh and Maugeri
Foundation Respiratory Failure questionnaire, and pulmonary function before and
after six months of nO2LT. RESULTS: At baseline, compared to COPDb, COPDe have
decreased sleep efficiency (SE) (67.5+/-6% vs. 76.9+/-3% p<0.05) and higher
arousals (A/I) (18.1+/-3 event/h vs. 8.7+/-1 event/h p<0.05). Oxygen desaturation
index (ODI) was increased during REM (7.1+/-1 event/h vs. 2.3+/-0.5 event/h
p<0.05). nO2LT in COPDe improves SE (77+/-4% vs. 67.5+/-6% p<0.05) and decreases
A/I (9+/-5 event/h vs. 18.1+/-3 event/h p<0.05). ODI during REM (3.5+/-2 event/h
vs. 7.1+/-1 p<0.05) decreases and quality of life (QoL) improves (MFR-28 total
56+/-22 vs 45+/-20 p<0.05), due to an improvement in cognitive abilities (45+/-30
vs 33+/-31 p<0.05) and daily activities (61+/-29 vs 53+/-21 p>0.05). In COPDb
nO2LT reduces ST90 (15+/-6% vs. 43+/-8% p<0.05) less than in COPDe (15+/-6% vs.
8+/-4% p<0.05); improves A/I (10+/-2 event/h vs. 8.7+/-1 p<0.05) and there is no
evidence of an improvement in QoL. CONCLUSIONS: Six months of nO2LT improve
quality of life in COPDe, not in COPDb. We found a difference in sleep quality
between COPDe and COPDb.
PMID- 27614377
TI - The efficacy and safety of selective granulocyte and monocyte apheresis for
inflammatory bowel disease: A meta-analysis.
PMID- 27614378
TI - Fibrillatory pattern of dissociated venous activity after pulmonary vein
isolation: Novel characteristics for remnant foci of a trigger ectopy for atrial
fibrillation.
AB - BACKGROUND: Dissociated pulmonary vein activity (DPVA), defined as isolated
intrinsic ectopic beats observed after successful pulmonary vein (PV) isolation,
indicates the presence of remnant foci of trigger ectopy but has yet to be
extensively studied. We investigated the correlation between DPVA and the PV
triggers of atrial fibrillation (AF). METHOD AND RESULTS: Consecutive 110
patients undergoing AF ablation were enrolled. We defined trigger ectopy as
documented ectopic foci observed to spontaneously initiate AF. Trigger ectopy was
detected in 62 (56%) patients. DPVA in at least one PV was detected in 95 (86%)
patients. Of the 440 isolated PVs, we recognized trigger ectopy in 73 (16%) PVs
(culprit PVs) and DPVA in 184 (42%) PVs. DPVA was more frequently observed in
culprit PVs than in non-culprit PVs [59% vs. 39%; odds ratio (OR)=2.3; p=0.001].
The concordance ratio of culprit PV was 67% (8/12) in PV with fibrillatory DPVA,
20% (35/172) in PV with non-fibrillatory DPVA, and 12% (30/256) in PV without
DPVA. Fibrillatory DPVA was more frequently observed in culprit PVs than non
fibrillatory DPVA (OR=7.8; p=0.001). Non-PV foci were observed in 10 (11%) of the
95 patients with DPVA and 5 (33%) of the 15 patients without DPVA (OR=4.3;
p=0.02). No significant difference in the frequency of AF recurrence was observed
between them. CONCLUSIONS: Fibrillatory DPVA was found to be strongly associated
with trigger ectopy of AF. Non-fibrillatory DPVA might merely indicate the
existence of bystander ectopic foci located inside PVs. Non-PV ectopic foci were
frequently observed in patients without DPVA.
PMID- 27614380
TI - Remission from substance use disorders: A systematic review and meta-analysis.
AB - OBJECTIVE: This paper presents a systematic review and meta-analysis of available
evidence on remission rates for substance use disorders (SUDs), providing
weighted mean estimates of SUD remission rates. The review also explores study
level characteristics that may explain variations in remission rates across
studies. METHODS: A comprehensive search strategy identified studies published
between 2000 and 2015 with follow-up periods of at least three years or reported
lifetime remission outcomes for potential inclusion in the review. Remission was
defined as not meeting diagnostic criteria for abuse or dependence for a minimum
period of six months, as of final follow-up. A single-group summary meta-analysis
was performed. Pooled estimated annual remission rates (PEARRs) were calculated.
Meta-regression techniques and subgroup analyses were used to explore the
association between study remission rates and key selected variables. RESULTS: Of
8855 studies identified, 21 met the eligibility criteria. The results suggested
that 35.0% to 54.4% of individuals with SUDs achieved remission, and this
occurred after a mean follow-up period of 17 years. The PEARRs projected few
cases of SUD remission, between 6.8% and 9.1% in any given year. Studies that
reported higher remission rates had longer follow-up periods, and lower sample
retention rates. CONCLUSIONS: Results support the contention that SUDs are more
likely to be "chronic" or long term disorders than acute disorders for a
substantial number of individuals. However, more longitudinal research is
required. Treatment geared to chronicity, such as assertive community treatment
and intensive case management, needs to be more readily available for SUD
populations.
PMID- 27614379
TI - The balloon-expandable Edwards Sapien 3 valve is superior to the self-expanding
Medtronic CoreValve in patients with severe aortic stenosis undergoing
transfemoral aortic valve implantation.
AB - BACKGROUND: Residual paravalvular moderate or severe aortic regurgitation (AR)
has been an independent risk factor for mortality after transcatheter aortic
valve implantation (TAVI). The design of the third generation Edwards Sapien 3
(ES3; Edwards Lifesciences, Irvine, CA, USA) valve was optimized with an outer
skirt to address the issue of paravalvular AR. METHODS AND RESULTS: We compared
100 consecutive patients treated with the ES3 for severe aortic stenosis with 100
patients treated with the Medtronic CoreValve (CV; Medtronic, Minneapolis, MN,
USA) (Clinical Trial Registration: NCT02162069). We evaluated post-procedural AR,
rate of permanent pacemaker implantation, device success, and 30-day clinical
outcome according to the criteria of the Second Valve Academic Research
Consortium (VARC-2). Frequency of post-procedural moderate or severe AR was
significantly lower with ES3 compared to CV (0% vs. 20%, p<0.01), none or trace
AR significantly higher with ES3 (69% vs. 38%, p<0.01) as well as device success
(97% vs. 73%, p<0.01). There was a significantly lower need for permanent
pacemaker implantation with ES3 compared with CV (14% vs. 31%, p<0.01).
Cardiovascular mortality at 30 days was significantly lower with ES3 (0% vs. 6%,
p=0.01), and the combined endpoint "early safety" was met significantly less with
ES3 (10% vs. 21% with CV, p=0.03). CONCLUSIONS: Transfemoral TAVI with the ES3
compared with the CV was associated with a significantly lower rate of moderate
or severe AR, significantly lower need for pacemaker implantation, and a
significantly higher rate of device success according to VARC-2.
PMID- 27614382
TI - Corrigendum to "Cardiovascular side-effects and insulin secretion after
intravenous administration of radiolabeled Exendin-4 in pigs" [Nucl Med Biol 43
(2016) 397-402].
PMID- 27614381
TI - Dimethoxy Curcumin Induces Apoptosis by Suppressing Survivin and Inhibits
Invasion by Enhancing E-Cadherin in Colon Cancer Cells.
AB - BACKGROUND Dimethoxy curcumin (DMC) is a kind of lipophilic analog of curcumin
with great improvement in chemical and metabolic stability. DMC has been studied
in breast and renal cancer, but no research in colon cancer has been found yet.
MATERIAL AND METHODS Two colon cancer cells (HT-29 and SW480) and one normal
human colon mucosal epithelial cell (NCM460) were used in this study. We studied
the effect of DMC on the proliferation in vitro and in vivo. Transwell migration
assay was used to estimate the inhibition of DMC on invasion. Moreover, the
expressions of PARP, caspase-3, survivin and E-cadherin were detected to uncover
the related signaling pathways by western blotting assay both in vitro and in
vivo. RESULTS DMC significantly inhibited the growth of colon cancer cells in
dose-dependent manner; IC50 for DMC was calculated to be 43.4, 28.2 and 454.8uM
on HT-29, SW480 and NCM460. DMC significantly increased the apoptosis in both HT
29 (p=0.0051) and SW480 (p=0.0013) cells in vitro, and significantly suppressed
the growth of both cell lines in vivo. Moreover, DMC reduced the number of
migrated cells in both HT-29 (p=0.007) and SW480 (p=0.004) cells. By western
blotting analysis, the cleavage of pro-caspases-3 and PARP were clearly induced
by DMC to their active form, while the expression of survivin was reduced and E
cadherin was enhanced in both cells in vitro and in vivo. CONCLUSIONS DMC may
exert an effective anti-tumor effect in colon cancer cells by down-regulating
survivin and upregulating E-cadherin.
PMID- 27614383
TI - The Effects of the Menstrual Cycle on Vibratory Characteristics of the Vocal
Folds Investigated With High-Speed Digital Imaging.
AB - OBJECTIVES: This study investigated the effect of menstrual cycle on vocal fold
vibratory characteristics in young women using high-speed digital imaging. This
study examined the menstrual phase effect on five objective high-speed imaging
parameters and two self-rated perceptual parameters. The effects of oral birth
control use were also investigated. METHODS: Thirteen subjects with no prior
voice complaints were included in this study. All data were collected at three
different time periods (premenses, postmenses, ovulation) over the course of one
menstrual cycle. For five of the 13 subjects, data were collected for two
consecutive cycles. Six of 13 subjects were oral birth control users. From high
speed imaging data, five objective parameters were computed: fundamental
frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic
richness factor, and ratio of first and second harmonics. They were supplemented
by two self-rated parameters: Reflux Severity Index and perceptual voice quality
rating. Analysis included mixed model linear analysis with repeated measures.
RESULTS: Results indicated no significant main effects for menstrual phase,
between-cycle, or birth control use in the analysis for mean fundamental
frequency, fundamental frequency deviation, harmonics-to-noise ratio, harmonic
richness factor, first and second harmonics, Reflux Severity Index, and
perceptual voice quality rating. Additionally, there were no interaction effects.
CONCLUSIONS: Hormone fluctuations observed across the menstrual cycle do not
appear to have direct effect on vocal fold vibratory characteristics in young
women with no voice concerns. Birth control use, on the other hand, may have
influence on spectral richness of vocal fold vibration.
PMID- 27614385
TI - [History of kidney transplantation surgery].
AB - OBJECTIVES: To perform a state of the art about the history of kidney
transplantation. MATERIAL AND METHODS: An exhaustive systematic review of the
scientific literature was performed in the Medline database
(http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different
associations of the following keywords (MESH): kidney transplantation, history,
vascular anastomosis. RESULTS: From the first vascular ligations to the discovery
of ciclosporin, the history of organ transplantation was made of surgical bets
and medical discoveries, such as blood group, HLA-system, immunity, etc. The
audacity of some surgeons led to the onset of renal transplantation as the
treatment of choice for end stage renal disease. CONCLUSION: This article aims to
describe the first surgical methods for vascular anastomosis and renal
transplantation. Through a comprehensive search within the archives of the French
National Library, the authors provide a precise description of the first renal
transplantations performed, the technique that have been used and their authors.
PMID- 27614384
TI - [Interest of infiltration of Impar node in rebel vulvodynia: About a series of 8
cases].
AB - INTRODUCTION: Vulvodynia is a common and debilitating disease, for which
treatments are often of limits efficacy. As the Impar node receives nociceptive
afferents from pelvis and perineum, it is a potential therapeutic target to treat
pain in this region. The objective of the study was to evaluate the relevance of
ropivacaine Impar node infiltration in patients suffering from rebel vulvodyny.
METHODS: This was a retrospective, single-center study. The Impar node
infiltrations were performed by a single operator in eight patients suffering
from rebel vulvodynia. Ropivacaine and iopamidol were administered in prone
position with a lateral approach under scanner. The anaesthetic diagnostic block
of the Impar node was positive in all eight patients included in the study.
Thereafter these patients benefited of 2 additional therapeutic infiltrations.
Subsequently, an infiltration of the node with 100UI of botulinum toxin was
performed in two patients with a bilateral approach under scanner. The analgesic
efficacy was evaluated by a Visual Analogic Scale (VAS) before, immediately
after, and at day 15 following the infiltration. A subjective evaluation of pain
comprising the percentage of overall improvement and duration of analgesic
efficacy was performed after the third infiltration. RESULTS: Comparison of the
VAS before and immediately after the Impar block showed in the first anesthetic
block a significant decrease in pain median VAS from 51/100 to 16/100 (P=0.01).
Similarly, for the second block, VAS decreased from 52.5/100 to 15/100 (P=0.02).
The maximal pain reported on Day 15, was significantly lower after the third
infiltration than that after the first (P=0.03). Five patients reported an
overall improvement in their quality of life of over 50%, which lasted an average
of six weeks. A long lasting effectiveness was obtained in the two patients who
benefited of the botulinum toxin. CONCLUSION: The infiltration of Impar node is
an interesting technique for patients suffering of rebel vulvodynia. LEVEL OF
EVIDENCE: 4.
PMID- 27614386
TI - [HoLEP learning curve: Toward a standardised formation and a team strategy].
AB - AIM: Holmium laser enucleation of prostate (HoLEP) is renowned for the difficulty
of its learning curve. Our aim was to evaluate the interest of a three-step
tutorial in the HoLEP learning curve, in a university center. METHODS: It is a
retrospective, monocentric study of the 82 first procedures done consecutively by
the same operator with a proctoring in early experience and after 40 procedures.
For all patients were noted: enucleation efficiency (g/min), morcellation
efficiency (g/min), percentage of enucleated tissue (enucleated tissue/adenome
weigth evaluated by ultrasonography. g/g), perioperative morbidity (Clavien),
length of hospital stay, length of urinary drainage, functional outcomes at short
and middle term (Qmax, post-void residual volume [PVR], QOL scores and IPSS at 3
and 6months). RESULTS: Enucleation and morcellation efficiency were significantly
higher after the second proctoring (0.87 vs 0.44g/min; P<0.0001 and 4.2 vs
3.37g/min, P=0.038, respectively) so as the prostatic volume (43.5 vs 68.1mL,
P=0.0001). Percentage of enucleated tissue was higher in the second group,
however, the difference was not significant (69.5% vs 80.4%, P=0.03). Per- and
postoperative complications, hospital length of stay, urinary drainage length and
functional results at 3 and 6months were not significantly different. CONCLUSION:
The learning curve did not interfere with functional results. The second
proctoring was essential to us in order to grasp the technique. These data
underlined the necessity of a pedagogic reflexion in order to built a
standardized formation technique to the HoLEP. LEVEL OF EVIDENCE: 4.
PMID- 27614387
TI - CRISPR/Cas9-mediated knockout of p22phox leads to loss of Nox1 and Nox4, but not
Nox5 activity.
AB - The NADPH oxidases are important transmembrane proteins producing reactive oxygen
species (ROS). Within the Nox family, different modes of activation can be
discriminated. Nox1-3 are dependent on different cytosolic subunits, Nox4 seems
to be constitutively active and Nox5 is directly activated by calcium. With the
exception of Nox5, all Nox family members are thought to depend on the small
transmembrane protein p22phox. With the discovery of the CRISPR/Cas9-system, a
tool to alter genomic DNA sequences has become available. So far, this method has
not been widely used in the redox community. On such basis, we decided to study
the requirement of p22phox in the Nox complex using CRISPR/Cas9-mediated
knockout. Knockout of the gene of p22phox, CYBA, led to an ablation of activity
of Nox4 and Nox1 but not of Nox5. Production of hydrogen peroxide or superoxide
after knockout could be rescued with either human or rat p22phox, but not with
the DUOX-maturation factors DUOXA1/A2. Furthermore, different mutations of
p22phox were studied regarding the influence on Nox4-dependent H2O2 production.
P22phox Q130* and Y121H affected maturation and activity of Nox4. Hence, Nox5
dependent O2*- production is independent of p22phox, but native p22phox is needed
for maturation of Nox4 and production of H2O2.
PMID- 27614388
TI - Does Release of the Superficial Medial Collateral Ligament Result in Clinically
Harmful Effects After the Fixation of Medial Meniscus Posterior Root Tears?
AB - PURPOSE: To investigate pain and tenderness, stress testing, clinical outcome
scores, complications, and operation time at 24 months and magnetic resonance
imaging (MRI) analysis at 12 months after the release of the distal attachment of
the superficial medial collateral ligament (sMCL) during medial meniscus
posterior root tear (MMPRT) fixation. METHODS: Patients who received MMPRT
fixation with a follow-up of at least 2 years were included. During fixation, the
release of the distal attachment of the sMCL on the proximal tibia was performed
to improve visualization and provide sufficient working space. Pain and
tenderness at the released area, manual valgus stress tests of 30 degrees and 0
degrees flexion (grade 0/1/2/3), and subjective instability during weight
bearing were evaluated serially at postoperative 3, 6, 12, and 24+ months. The
contour of detachment area was assessed using MRI 12 months postoperatively. As a
subgroup analysis, tourniquet time (minutes) and final clinical scores were
compared between release and nonrelease groups. RESULTS: The numbers of
participants in the release and nonrelease groups were 118 and 20 patients, and
their mean follow-up durations were 42.4 +/- 19.3 (24-95) and 37.2 +/- 7.8 (30
55) months, respectively. In the release group, percentages of patients with pain
and tenderness at 3 months were 15% and 18%, respectively; however, no patients
had symptoms at 12 months. In valgus stress tests (30 degrees , 0 degrees ), 12%
and 2% of patients showed grade 1 laxity at 3 months, and 7% had grade 1 laxity
in only 30 degrees flexion at the final follow-up. However, no patients had
subjective valgus laxity. An intact contour was confirmed in all cases among 94
patients checked by performing follow-up MRI. Tourniquet time was significantly
shorter in the release group (42.4 +/- 19.3) than in the nonrelease group (58.5
+/- 9.5; P < .001). Between release and nonrelease groups, Lysholm (84.4 +/-
12.1, 88.1 +/- 12.8; P = .117) and International Knee Documentation Committee
scores (73.6 +/- 11.2, 77.5 +/- 11.9; P = .112) did not differ. CONCLUSIONS: The
release of the distal attachment of the sMCL during fixation of MMPRT did not
result in pain and tenderness, residual instability, and complication. An intact
contour of the sMCL was confirmed in all cases with MRI. This procedure reduced
operation time and showed similar clinical results when compared between the
release and nonrelease groups. However, this study had low power to detect the
difference for clinical scores between the 2 groups. LEVEL OF EVIDENCE: Level IV,
therapeutic case series.
PMID- 27614389
TI - Quality of Life and Functional Results of Arthroscopic Partial Repair of
Irreparable Rotator Cuff Tears.
AB - PURPOSE: To evaluate the minimum 2-year results and possible outcomes of
arthroscopic partial repair in different patterns of irreparable rotator cuff
tears (RCTs). METHODS: Patients suffering from an irreparable supraspinatus and a
reparable infraspinatus tendons who underwent arthroscopic partial repair with a
minimum 24-month follow-up were included in this study. The Constant and Murley
score (CMS) was used to assess patients' functionality pre- and postoperatively.
Postoperative patient assessment included the Simple Shoulder Test (SST) and the
Short Form Health Survey questionnaire (SF-36). A postoperative range of motion,
CMS, and strength were compared with the contralateral side. Postoperative SF-36
was compared with age- and sex-matched norms. RESULTS: Ninety patients (95
shoulders) were reviewed after a mean follow-up of 7 (range 2-12) years. The
subscapularis tendon was intact in 80 shoulders and torn but completely reparable
in the remaining 15 shoulders. The CMS improved from 39.1 +/- 8.4 (10-61) to 76.3
+/- 9.7 (32-93) (P < .001). The mean postoperative SST was 9.1 +/- 2.2 (1-12).
Although the patients had lower postoperative abduction and internal rotation,
strength in abduction and CMS in comparison with the measurements from the
contralateral side, the median postoperative SF-36 physical and mental component
summaries were 98% and 100% of the matched norms. No significant differences were
found in postoperative outcomes according to the RCT pattern. Males showed
significantly higher strengths in abduction (B = -1.384, 95% confidence interval
[CI] -2.144 to -0.624, eta2 = 0.123, P < .001, 95% power), external rotation (B =
-3.646, 95% CI -5.2 to -2.092, eta2 = 0.189, P < .001, 100% power), and internal
rotation (B = -3.867, 95% CI -5.676 to -2.057, eta2 = 0.162, P < .001, 99% power)
than females. Significantly higher ranges of abduction (eta2 = 0.431, P = .019,
98% power) and external rotation (eta2 = 0.417, P < .03, 97% power) were noted in
younger patients. Higher strengths in abduction (eta2 = 0.495, P = .002, 100%
power) and internal rotation (eta2 = 0.464, P = .006, 99% power) were also
reported in these patients. CONCLUSIONS: When there is an irreparable
supraspinatus but there is still the possibility to repair the infraspinatus and
subscapularis, the arthroscopic partial cuff repair should be considered as an
effective surgical option. Indeed, a significant clinical improvement can be
achieved and, differently from pure symptomatic surgical procedures, this
technique represents a reasonable effort to restore, at least in part, the
shoulder joint functionality. Successful and reliable results can be expected at
an average 7-year follow-up, regardless of the RCT pattern. Female and older
patients have a greater likelihood of lower functional outcomes. LEVEL OF
EVIDENCE: Level IV, therapeutic case series.
PMID- 27614390
TI - Proximity of the Triangular Fibrocartilage Complex to Key Surrounding Structures
and Safety Assessment of an Arthroscopic Repair Technique: A Cadaveric Study.
AB - PURPOSE: To quantify the distance of the dorsal ulnar sensory branch, floor of
the extensor carpi ulnaris (ECU) subsheath, and ulnar neurovascular bundles from
the triangular fibrocartilage complex (TFCC), and secondarily to assess the
safety of an all-inside arthroscopic repair of the TFCC with a commonly used
meniscal repair device with respect to the aforementioned structures. METHODS: A
custom K-wire with 1-mm gradation was used to determine the distance of at-risk
structures from the periphery of the TFCC in 13 above-elbow human cadaver
specimens. An all-inside repair of the TFCC at the location of a Palmer 1B tear
was then performed using a commonly employed meniscal repair device. The distance
from the deployed devices to the structure in closest proximity was then measured
using digital calipers. RESULTS: The mean distance from the deployed device to
the nearest structure of concern for iatrogenic injury was 9.4 mm (range, 5-15
mm). The closest structure to iatrogenic injury was usually, but not always, the
dorsal ulnar sensory nerve in 9 of 13 wrists (69.2%) at 9.3 mm (range, 5-15 mm);
on 3 occasions it was instead the ulnar nerve (23.1%) at 9.5 mm (range, 9-10 mm),
and on 1 occasion 6 mm from the flexor digitorum profundus to the little finger
(7.7%). Forearm rotation had no significant effect on measured distances (ulnar
nerve: P = .98; dorsal sensory: P = .89; ECU: P = .90). The largest influence of
forearm rotation was a 0.4-mm difference between pronation and supination with
respect to the distance of the TFCC periphery on the ECU subsheath. CONCLUSIONS:
An all-inside arthroscopic TFCC repair using a commonly used meniscal repair
device appears safe with respect to nearby neurovascular structures and tendons
under typical arthroscopic conditions. CLINICAL RELEVANCE: An all-inside
arthroscopic TFCC repair using a commonly employed meniscal repair device appears
safe in terms of proximity to important structures although further clinical
investigation is warranted.
PMID- 27614391
TI - Results of Hyaluronic Acid-Based Cell-Free Scaffold Application in Combination
With Microfracture for the Treatment of Osteochondral Lesions of the Knee: 2-Year
Comparative Study.
AB - PURPOSE: To determine the clinical and radiographic efficacy of hyaluronic acid
based cell-free scaffold applied in combination with microfracture versus
microfracture alone in patients with focal osteochondral lesion of the knee
joint. METHODS: Clinical data of 43 patients between 24 and 55 years of age were
evaluated. Hyaluronic acid-based cell-free scaffold was applied in combination
with microfracture for 19 knees (group 1), whereas microfracture alone was the
surgical intervention for 24 knees (group 2). All lesions were Outerbridge grade
III or IV with a mean size of 3.6 +/- 1.3 cm2. The mean follow-up time was 25.7
months. Visual analog scale (VAS), Lysholm knee score, and Tegner activity scale
were the instruments used to evaluate the clinical status. Magnetic resonance
observation of cartilage repair tissue (MOCART) system was used to analyze the
characteristics of repair tissue. RESULTS: Better VAS and Lysholm scores were
detected in group 1 at 12 and 24 months (P = .019 and P = .025). According to the
Tegner activity scale, group 1 had also better activity level at the end of 24
months after surgery (P = .020). The mean time from surgery to return to
nonimpact sports activities was 7.8 months in group 1, whereas it was 9.2 months
in group 2 (P = .013). Complete repair with the filling of the defect was
achieved in 7 (36.8%) of the knees in group 1, whereas it was 4 (16.6%) of the
knees in group 2 according to the MOCART system at 24 months. CONCLUSIONS: Single
stage regenerative cartilage surgery using hyaluronic acid-based cell-free
scaffold in combination with microfracture for focal osteochondral lesions of the
knee revealed promising clinical outcomes at 24 months of follow-up, but the
clinical significance of the differences seen is simply not known. LEVEL OF
EVIDENCE: Level III, retrospective comparative study.
PMID- 27614392
TI - Cost analysis of surgical treatment for pelvic organ prolapse by laparoscopic
sacrocolpopexy or transvaginal mesh.
AB - OBJECTIVES: The objective of this study is to compare direct costs of repairing
pelvic organ prolapse by laparoscopic sacrocolpopexy (LS) against vaginal mesh
(VM). Our hypothesis is the correction of pelvic organ prolapse by LS has a
similar cost per procedure compared to VM. MATERIAL AND METHODS: We made a
retrospective comparative analysis of medium cost per procedure of first 69
consecutive LS versus first 69 consecutive VM surgeries. We calculate direct cost
for each procedure: structural outlays, personal, operating room occupation,
hospital stay, perishable or inventory material and prosthetic material. Medium
cost per procedure were calculated for each group, with a 95% confidence
interval. RESULTS: LS group has a higher cost related to a longer length of
surgery, higher operating room occupation and anesthesia; VM group has a higher
cost due to longer hospital stay and more expensive prosthetic material.
Globally, LS has a lower medium cost per procedure in comparison to VM (5,985.7
?+/-1,550.8 ? vs. 6,534.3 ?+/-1,015.5 ?), although it did not achieve statistical
signification. CONCLUSIONS: In our midst, pelvic organ prolapse surgical
correction by LS has at least similar cost per procedure compared to VM.
PMID- 27614393
TI - Applying Proteomics to Study Crosstalk at the Cartilage-Subchondral Bone
Interface in Osteoarthritis: Current Status and Future Directions.
PMID- 27614394
TI - A History of Falls Should Be Recorded in All Preoperative Patients.
PMID- 27614396
TI - Transforming Growth Factor-beta1 as a Predictor for the Development of
Hepatocellular Carcinoma: A Nested Case-Controlled Study.
AB - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) reportedly acts as a
tumor suppressor in tumorigenesis. However, little is known as to how TGF-beta1
concentrations change prior to the development of hepatocellular carcinoma (HCC)
in humans. We examined the association between the serum TGF-beta1 concentrations
and death from HCC to determine whether the serum TGF-beta1 can be a predictor of
incident HCC. METHODS: We conducted a nested case-controlled study of
participants in the Japan Collaborative Cohort Study for Evaluation of Cancer
Risk. We used a conditional logistic regression analysis to estimate the adjusted
relative risks (aRRs) of death from HCC according to the serum TGF-beta1
concentrations among 1940 participants including 83 patients with HCC and 1857
controls matched for age, sex, and hepatitis C virus (HCV)-antibody
seropositivity. FINDINGS: When serum TGF-beta1 was modelled as a continuous
variable, the aRR of death from HCC associated with a decrement of 7.9ng/mL (one
standard deviation) in the serum TGF-beta1 concentrations was 2.3 (95% CI 1.7
3.0, P<0.001) for all the subjects. The area under the receiver operating
characteristic curve for the serum TGF-beta1 concentrations was 0.78 (P<0.05).
INTERPRETATION: Our finding suggests that TGF-beta1 serves as a predictor for
HCC.
PMID- 27614397
TI - Monitoring of metal pollution in waterways across Bangladesh and ecological and
public health implications of pollution.
AB - Using innovative artificial mussels technology for the first time, this study
detected eight heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, U, Zn) on a regular basis in
waterways across Bangladesh (Chittagong, Dhaka and Khulna). Three heavy metals,
viz. Co, Cr and Hg were always below the instrumental detection levels in all the
sites during the study period. Through this study, seven metal pollution "hot
spots" have been identified, of which, five "hot spots" (Cu, Fe, Mn, Ni, Pb) were
located in the Buriganga River, close to the capital Dhaka. Based on this study,
the Buriganga River can be classified as the most polluted waterway in Bangladesh
compared to waterways monitored in Khulna and Chittagong. Direct effluents
discharged from tanneries, textiles are, most likely, reasons for elevated
concentrations of heavy metals in the Buriganga River. In other areas (Khulna),
agriculture and fish farming effluents may have caused higher Cu, U and Zn in the
Bhairab and Rupsa Rivers, whereas untreated industrial discharge and ship
breaking activities can be linked to elevated Cd in the coastal sites
(Chittagong). Metal pollution may cause significant impacts on water quality
(irrigation, drinking), aquatic biodiversity (lethal and sub-lethal effects),
food contamination/food security (bioaccumulation of metals in crops and
seafood), human health (diseases) and livelihoods of people associated with
wetlands.
PMID- 27614395
TI - Development and Validation of a Novel Recurrence Risk Stratification for Initial
Non-muscle Invasive Bladder Cancer in Asia.
AB - BACKGROUND: Some risk classifications to determine prognosis of patients with non
muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical
setting. We investigated whether the EORTC (European Organization for Research
and Treatment of Cancer) risk stratification is useful to predict recurrence and
progression in Japanese patients with NMIBC. In addition, we developed and
validated a novel, and simple risk classification of recurrence. METHODS: The
analysis was based on 1085 patients with NMIBC at six hospitals. Excluding
recurrent cases, we included 856 patients with initial NMIBC for the analysis.
The Kaplan-Meier method with the log-rank test were used to calculate recurrence
free survival (RFS) rate and progression-free survival (PFS) rate according to
the EORTC risk classifications. We developed a novel risk classification system
for recurrence in NMIBC patients using the independent recurrence prognostic
factors based on Cox proportional hazards regression analysis. External
validation was done on an external data set of 641 patients from Kyorin
University Hospital. FINDINGS: There were no significant differences in RFS and
PFS rates between the groups according to EORTC risk classification. We
constructed a novel risk model predicting recurrence that classified patients
into three groups using four independent prognostic factors to predict tumour
recurrence based on Cox proportional hazards regression analysis. According to
the novel recurrence risk classification, there was a significant difference in 5
year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk
groups (P<0.001). INTERPRETATION: As the EORTC risk group stratification may not
be applicable to Asian patients with NMIBC, our novel classification model can be
a simple and useful prognostic tool to stratify recurrence risk in patients with
NMIBC. FUNDING: None.
PMID- 27614398
TI - Photocatalytic degradation kinetics of naphthenic acids in oil sands process
affected water: Multifactorial determination of significant factors.
AB - Oil sands process-affected water (OSPW) is generated as a byproduct of bitumen
extraction in Canada's oil sands. Due to the water's toxicity, associated with
dissolved acid extractable organics (AEO), especially naphthenic acids (NAs),
along with base-neutral organics, OSPW may require treatment to enable safe
discharge to the environment. Heterogeneous photocatalysis is a promising
advanced oxidation process (AOP) for OSPW remediation, however, predicting
treatment efficacy can be challenging due to the unique water chemistry of OSPW
from different tailings ponds. The objective of this work was to study various
factors affecting the kinetics of photocatalytic AEO degradation in OSPW. The
rate of photocatalytic treatment varied significantly in two different OSPW
sources, which could not be accounted for by differences in AEO composition, as
studied by high resolution mass spectrometry (HRMS). The effects of inorganic
water constituents were investigated using factorial and response surface
experiments, which revealed that hydroxyl (HO) radical scavenging by iron (Fe3+)
and bicarbonate (HCO3-) inhibited the NA degradation rate. The effects of NA
concentration and temperature on the treatment kinetics were also evaluated in
terms of Langmuir-Hinshelwood and Arrhenius models; pH and temperature were
identified as weak factors, while dissolved oxygen (DO) was critical to the photo
oxidation reaction. Accounting for all of these variables, a general empirical
kinetic expression is proposed, enabling prediction of photocatalytic treatment
performance in diverse sources of OSPW.
PMID- 27614399
TI - Less is more.
PMID- 27614400
TI - The interactome of CCT complex - A computational analysis.
AB - The eukaryotic chaperonin, CCT (Chaperonin Containing TCP1 or TriC-TCP-1 Ring
Complex) has been subjected to physical and genetic analyses in S. cerevisiae
which can be extrapolated to human CCT (hCCT), owing to its structural and
functional similarities with yeast CCT (yCCT). Studies on hCCT and its
interactome acquire an additional dimension, as it has been implicated in several
disease conditions like neurodegeneration and cancer. We attempt to study its
stress response role in general, which will be reflected in the aspects of human
diseases and yeast physiology, through computational analysis of the interactome.
Towards consolidating and analysing the interactome data, we prepared and
compared the unique CCT-interacting protein lists for S. cerevisiae and H.
sapiens, performed GO term classification and enrichment studies which provide
information on the diversity in CCT interactome, in terms of protein classes in
the data set. Enrichment with disease-associated proteins and pathways highlight
the medical importance of CCT. Different analyses converge, suggesting the
significance of WD-repeat proteins, protein kinases and cytoskeletal proteins in
the interactome. The prevalence of proteasomal subunits and ribosomal proteins
suggest a possible cross-talk between protein-synthesis, folding and degradation
machinery. A network of chaperones and chaperonins that function in combination
can also be envisaged from the CCT interactome-Hsp70 interactome analysis.
PMID- 27614401
TI - Which leukocyte subtypes can predict outcomes of acute coronary syndrome?
PMID- 27614402
TI - Contralesional Cathodal versus Dual Transcranial Direct Current Stimulation for
Decreasing Upper Limb Spasticity in Chronic Stroke Individuals: A Clinical and
Neurophysiological Study.
AB - BACKGROUND: Different transcranial direct current stimulation (tDCS) paradigms
have been implemented to treat poststroke spasticity, but discordant results have
been reported. OBJECTIVE: This study aimed to determine the efficacy and
persistence of dual tDCS (anode over affected motor cortex [M1] and cathode over
contralateral M1) compared with cathodal tDCS (cathode over contralateral M1) on
upper limb (UL) functional, behavioral, and neurophysiological measures in
chronic poststroke individuals. SUBJECTS AND METHODS: Ten subjects with UL
spasticity (7 men; mean 62 years; 8 ischemic stroke; years from event: 2.3 years)
were enrolled in a cross-over, double-blinded study. Cathodal and dual tDCS, both
preceded by 1 week of sham stimulation 1 month before real stimulation, were
applied with 3 months interval. Stimulating paradigm was 20 minutes for five
consecutive days in each block. Evaluations were performed before (T1), after
real or sham treatment (T2), and after 1 (T3), 4 (T4), and 8 weeks (T5).
Functional, behavioral, and neurophysiological tests were performed at each time.
RESULTS: Both tDCS paradigms decreased spasticity, increased strength, and
ameliorated behavioral scales. Cathodal tDCS was superior to dual tDCS in
reducing UL distal spasticity immediately after treatment (T2: cathodal > dual: P
= .023) and provided a higher and longer lasting reduction at proximal districts
(T3: cathodal > dual: P = .042; T4: cathodal > dual: P = .028; T5: cathodal >
dual: P = .05). These findings are supported by an H-reflex modulation (overall
time effect P > .002). CONCLUSIONS: Cathodal tDCS is slightly more effective than
dual tDCS in reducing distal UL spasticity in chronic poststroke subjects. A
modulation of spinal inhibitory mechanisms, demonstrated by H-reflex
modifications, supports this finding.
PMID- 27614403
TI - Safely Addressing Patients with Atrial Fibrillation to Early Anticoagulation
after Acute Stroke.
AB - BACKGROUND: It has been widely reported that anticoagulants (ACs) are underused
for primary and secondary prevention of ischemic stroke in patients with atrial
fibrillation (AFib). Furthermore, precise evidence-based guidelines about the
best timing for AC initiation after acute stroke are currently lacking. METHODS
AND RESULTS: In this retrospective, observational study, we analyzed prescription
trends in AFib patients with acute ischemic stroke who were hospitalized in four
neurologic stroke units of our region (Lombardia, Italy). In-hospital
antithrombotic prescription was performed in highly heterogeneous patterns. A
prestroke treatment with AC was the leading factor enhancing AC prescription
during hospitalization. The other factors promoting AC were male gender, younger
age, lower prestroke disability and stroke severity, and smaller stroke volumes.
AFib subtype influenced AC prescription only in AC-naive patients. Interestingly,
Congestive heart failure, Hypertension, Age higher than 75 years, Diabetes,
previous Stroke or TIA or thromboembolism, Vascular disease, Age 64-75 years,
female Sex (CHA2DS2-VASc) and Hypertension, Abnormal renal and liver function,
Stroke, Bleeding, Labile INRs, Elderly, Drugs and alcohol (HAS-BLED) scores were
not associated with AC prescription. However, patients who were treated with AC,
including early treatment (<48 hours), showed a low rate of bleeding.
CONCLUSIONS: Our findings potentially suggest that, although apparently
neglecting the common risk stratification tools, our neurologists were able to
select the more suitable candidates for prompt AC treatment. Further studies are
needed to develop new scoring systems to aid ischemic and hemorrhagic risk
estimation in the secondary prevention of stroke.
PMID- 27614404
TI - Case-Control Study of Impairments Associated with Recovery from "Pusher Syndrome"
after Stroke: Logistic Regression Analyses.
AB - BACKGROUND: Comparing cohorts with similar functional and motor status at
admission to inpatient rehabilitation may delineate demographics or impairments
associated with recovery from lateropulsion, also known as "pusher syndrome,"
after stroke based on lesion side. The aim of this case-control study was to
determine how demographics and severity of stroke impairments at admission to
inpatient rehabilitation distinguish patients who recover from lateropulsion from
those who do not. METHODS: Patients with admission motor Functional Independence
Measure (FIM) scores less than 31 and contralesional lower extremity Fugl-Meyer
motor scores less than 19 out of 34 were included. Burke Lateropulsion Scales
score of 2 or higher at the time of discharge from inpatient rehabilitation
indicated persistent lateropulsion; a score of 0 or 1 indicated resolved
lateropulsion. Logistic regression tests included age, gender, admission
Motricity Index score, limb placement error, and cognitive FIM score. chi2
analyses compared groups for neglect. RESULTS: For patients with left brain
lesion, older age and worse admission motor status distinguished those with
persistent lateropulsion at discharge. For right brain lesion, related factors
were older age, greater admission limb placement error, and lower cognitive FIM
scores. Visuospatial neglect did not influence recovery from lateropulsion.
CONCLUSIONS: Older age and severe impairments were associated with delayed
recovery from lateropulsion in a manner specific to lesion side in a sample with
motor and functional deficits. The study provides evidence that lesion side and
admission characteristics are useful in early decision making for the duration of
rehabilitation, selection of interventions, and discharge planning.
PMID- 27614405
TI - Player's success prediction in rugby union: From youth performance to senior
level placing.
AB - OBJECTIVES: The study questioned if and to what extent specific anthropometric
and functional characteristics measured in youth draft camps, can accurately
predict subsequent career progression in rugby union. DESIGN: Original research.
METHODS: Anthropometric and functional characteristics of 531 male players (U16)
were retrospectively analysed in relation to senior level team representation at
age 21-24. Players were classified as International (Int: National team and
international clubs) or National (Nat: 1st, 2nd and other divisions and dropout).
Multivariate analysis of variance (one-way MANOVA) tested differences between Int
and Nat, along a combination of anthropometric (body mass, height, body fat, fat
free mass) and functional variables (SJ, CMJ, t15m, t30m, VO2max). A discriminant
function (DF) was determined to predict group assignment based on the linear
combination of variables that best discriminate groups. Correct level assignment
was expressed as % hit rate. RESULTS: A combination of anthropometric and
functional characteristics reflects future level assignment (Int vs. Nat).
Players' success can be accurately predicted (hit rate=81% and 77% for Int and
Nat respectively) by a DF that combines anthropometric and functional variables
as measured at ~15 years of age, percent body fat and speed being the most
influential predictors of group stratification. CONCLUSIONS: Within a group of 15
year-olds with exceptional physical characteristics, future players' success can
be predicted using a linear combination of anthropometric and functional
variables, among which a lower percent body fat and higher speed over a 15m
sprint provide the most important predictors of the highest career success.
PMID- 27614406
TI - Thiazolidin-4-ones from 4-(methylthio)benzaldehyde and 4
(methylsulfonyl)benzaldehyde: Synthesis, antiglioma activity and cytotoxicity.
AB - The present study assessed the biological potential of fourteen 1,3-thiazolidin-4
ones evaluating the antiglioma effect through decreasing of cell viability of
glioblastoma multiform cells. The new compounds were efficient synthesized
through multicomponent or multicomponent one-pot procedures in moderate to good
yields (22-86%) from two arenealdehydes (4-(methylthio)benzaldehyde and 4
(methylsulfonyl)benzaldehyde), seven amines (aromatic and aliphatic) and
mercaptoacetic acid. The compounds were identified and characterized by GC/MS and
NMR, five of them by HRMS. Six thiazolidinones showed significant effect of
decreasing cell viability compared to standard drug TMZ at 100 MUM in 72 h in C6
cell line by MTT assay. The compounds 5b, 5e, 5g and 6e showed the best results
in the screening at 100 MUM and were analyzed at different concentrations (5, 25,
50, 100 and 250 MUM). Compounds 5b and 5e showed statistical difference at 5 MUM,
6e at 25 MUM and 5g at 50 MUM in 72 h of treatment. The cytotoxicity study in
primary astrocytes cells was evaluated and none of fourteen compounds showed
toxicity at 100 MUM, eight of them were not cytotoxic at 250 MUM, both in 72 h.
In addition, the propidium iodide assay demonstrated that the compounds might
induce cell death by necrosis. In conclusion, this work reports at least four
compounds (5b, 5e, 5g and 6e) with potential anti-tumor effect against
glioblastoma multiform cell presenting activity at low concentrations and safe
profile of cytotoxicity.
PMID- 27614407
TI - Balancing potency, metabolic stability and permeability in pyrrolopyrimidine
based EGFR inhibitors.
AB - The present study describes our continuous effort to develop epidermal growth
factor receptor (EGFR) inhibitors based on the 6-aryl-pyrrolo[2,3-d]pyrimidin-4
amine scaffold. The activity-ADME space has been evaluated by synthesizing 43 new
structures, including four variations of the 4-amino group and 34 different
substitution patterns in the 6-aryl moiety. Most of the new pyrrolopyrimidines
were highly active, with twelve analogues possessing lower IC50 values than the
commercial drug Erlotinib in enzymatic assays. Ten EGFR inhibitors were also
profiled in cell studies using the Ba/F3-EGFRL858R reporter cells, and all
revealed nanomolar activity. However, some of the privileged structures in terms
of potency had ADME short-comings: compounds containing amides, sulfonamides,
amine and hydroxymethyl substituents in the 6-aryl group had low permeability and
high efflux, derivatives having (R)-3-amino-3-phenylpropan-1-ol at C-4 induced
hERG inhibition properties, and metabolic lability was seen for compounds having
(S)-2-methoxy-1-phenylethan-1-amine at C-4. Based on a trade-off between
enzymatic activity, cellular potency and ADME properties, (S)-2-phenyl-2-((6
phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethan-1-ol appeared as the most
promising drug candidate. Cellular studies indicate this compound to have
therapeutic use in EGFR driven diseases.
PMID- 27614408
TI - Synthesis and biological evaluation of new benzimidazole-thiazolidinedione
hybrids as potential cytotoxic and apoptosis inducing agents.
AB - A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and
evaluated for their cytotoxic potential against a selected human cancer cell
lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a
normal breast epithelial cells (MCF10A). Among the tested compounds, 11p
exhibited promising cytotoxicity with IC50 value of 11.46 +/- 1.46 MUM on A549
lung cancer cell line and did not show significant toxicity on normal MCF10A
cells. Lung cancer cells (A549) have been used to know the mechanism of cell
growth inhibition and apoptosis inducing effect with compound 11p. The treatment
of A549 cells with 11p showed typical apoptotic morphology like cell shrinkage,
chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry
analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner.
Preliminary mechanistic studies suggested that the cell migration was inhibited
through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO
EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays
suggested the induction of apoptosis in A549 cells by compound 11p.
PMID- 27614409
TI - Novel urea and bis-urea primaquine derivatives with hydroxyphenyl or
halogenphenyl substituents: Synthesis and biological evaluation.
AB - A series of novel compounds 3a-j and 6a-j with primaquine and hydroxyl or halogen
substituted benzene moieties bridged by urea or bis-urea functionalities were
designed, synthesized and evaluated for biological activity. The title compounds
were prepared using benzotriazole as the synthon, through several synthetic
steps. 3-[3,5-Bis(trifluoromethyl)phenyl]-1-{4-[(6-methoxyquinolin-8
yl)amino]pentyl}urea (3j) was the most active urea and 1-[({4-[(6-methoxyquinolin
8-yl)amino]pentyl}carbamoyl)amino]-3-[3-(trifluoromethyl)phenyl]urea (6h) the
most active bis-urea derivative in antiproliferative screening in vitro against
eight tested cancer cell lines. Urea derivatives 3a-g with hydroxy group or one
halogen atom showed moderate antiproliferative effects against all the tested
cell lines, but stronger activity against breast carcinoma MCF-7 cell line, while
trifluoromethyl derivatives 3h-j showed antiproliferative effects against all the
tested cell lines in low micromolar range. Finally, bis-ureas with hydroxy and
fluoro substituents 6a-d showed extreme selectivity and chloro or bromo
derivatives 6e-g high selectivity against MCF-7 cells (IC50 0.1-2.6 MUM). p
Fluoro derivative 6d, namely 3-(4-fluorophenyl)-1-[({4-[(6-methoxyquinolin-8
yl)amino]pentyl}carbamoyl)amino]urea, is the most promising compound. Further
biological experiments showed that 6d affected cell cycle and induced cell death
of MCF-7 cell line. Due to its high activity against MCF-7 cell line (IC50 0.31
MUM), extreme selectivity and full agreement with the Lipinski's and Gelovani's
rules for prospective small molecular drugs, 6d may be considered as a lead
compound in development of breast carcinoma drugs. Urea 3b and almost all bis
ureas showed high antioxidant activity in DPPH assay, but urea derivatives were
more active in lipid peroxidation test. Only few compounds exhibited weak
inhibition of soybean lipoxygenase. Compound 3j exhibited the strongest
antimicrobial activity in susceptibility assay in vitro (MIC = 1.6-12.5 MUg ml
1).
PMID- 27614410
TI - Synthesis and evaluation of xanthine oxidase inhibitory and antioxidant
activities of 2-arylbenzo[b]furan derivatives based on salvianolic acid C.
AB - Xanthine oxidase (XO) is the key enzyme in humans which is related to a variety
of diseases such as gout, hyperuricemia and cardiovascular diseases. In this
work, a series of 2-arylbenzo[b]furan derivatives were synthesized based on
salvianolic acid C, and they were evaluated for xanthine oxidase inhibitory and
antioxidant activities. Compounds 5b, 6a, 6e and 6f showed potent xanthine
oxidase inhibitory activities with IC50 values ranging from 3.99 to 6.36 MUM,
which were comparable with that of allopurinol. Lineweaver-Burk plots analysis
revealed that the representative derivative 6e could bind to either xanthine
oxidase or the xanthine oxidase-xanthine complex, which exhibited a mixed-type
competitive mechanism. A DPPH radical scavenging assay showed most of the
hydroxyl-functionalized 2-arylbenzo[b]furan derivatives possessed the potent
antioxidant activity, which was further validated on LPS-stimulated RAW 264.7
macrophages model. The structure-activity relationships were preliminary analyzed
and indicated that the structural skeleton of 2-arylbenzo[b]furan and phenolic
hydroxyl groups played an important role in maintaining xanthine oxidase
inhibitory effect and antioxidant property for the series of derivatives.
Meanwhile, molecular docking studies were performed to further confirm the
structure-activity relationships and investigate the proposed binding mechanisms
of compounds 5d, 6d and 10d binding to the protein.
PMID- 27614411
TI - Synthesis and biological evaluation of new aryl-alkyl(alkenyl)-4
benzylpiperidines, novel Sigma Receptor (SR) modulators, as potential anticancer
agents.
AB - In the early 2000s, the Sigma Receptor (SR) family was identified as potential
"druggable" target in cancer treatment. Indeed, high density of SRs was found in
breast, lung, and prostate cancer cells, supporting the idea that SRs could play
a role in tumor growth and progression. Moreover, a link between the degree of SR
expression and tumor aggressiveness has been postulated, justified by the
presence of SRs in high metastatic-potential cancer cells. As a consequence,
considerable efforts have been devoted to the development of small molecules
endowed with good affinity towards the two SR subtypes (S1R and S2R) with
potential anticancer activity. Herein, we report the synthesis and biological
profile of aryl-alkyl(alkenyl)-4-benzylpiperidine derivatives - as novel
potential anticancer drugs targeting SR. Among them, 3 (RC-106) exhibited a
preclinical profile of antitumor efficacy on a panel of cell lines representative
of different cancer types (i.e. Paca3, MDA-MB 231) expressing both SRs, and
emerged as a hit compound of a new class of SR modulators potentially useful for
the treatment of cancer disease.
PMID- 27614412
TI - Potential therapeutic application of small molecule with sulfonamide for
chondrogenic differentiation and articular cartilage repair.
AB - The restoration of damaged articular cartilage is a long-pursued goal in
regenerative medicine. Chondrocyte-specific differentiation of mesenchymal stem
cells (MSCs) may be an effective means of repairing damaged cartilage. We
identified small molecule 6 with sulfonamide as an agent that promotes specific
chondrogenic differentiation of human adipose-derived MSCs (hASCs). Unlike other
chondrogenic differentiation media composed of various defined components, simply
adding compound 6 into culture medium was sufficient to induce chondrogenesis in
this study. In an animal osteoarthritis model, both the small molecule 6 and the
6-treated hASCs exhibited enhanced recovery of injured articular cartilage. This
work provides new insight into MSC differentiation induced by small molecules and
potential new therapeutic approaches for articular cartilage injury.
PMID- 27614413
TI - Synthesis and antibacterial evaluation of hamacanthin B analogues.
AB - Hamacanthins are a class of antibacterial bisindole alkaloids isolated from
marine sponges. Based on structure-activity relationships and in silico MRSA PK
binding analysis of these bisindole alkaloids, the authors designed new
hamacanthin B derivatives and evaluated their antibacterial activities against
drug-resistant pathogens. Racemates of the synthetic products were resolved into
their enantiomers by chiral separation using a cellulose column, and
antibacterial activities were compared. Unsaturation of the central heterocyclic
ring structure and bromine substitution at the indole moiety were found to
enhance the antibacterial activities of hamacanthin B analogues.
PMID- 27614414
TI - Temozolomide analogs with improved brain/plasma ratios - Exploring the
possibility of enhancing the therapeutic index of temozolomide.
AB - Temozolomide is a chemotherapeutic agent that is used in the treatment of
glioblastoma and other malignant gliomas. It acts through DNA alkylation, but
treatment is limited by its systemic toxicity and neutralization of DNA
alkylation by upregulation of the O6-methylguanine-DNA methyltransferase gene.
Both of these limiting factors can be addressed by achieving higher
concentrations of TMZ in the brain. Our research has led to the discovery of new
analogs of temozolomide with improved brain:plasma ratios when dosed in vivo in
rats. These compounds are imidazotetrazine analogs, expected to act through the
same mechanism as temozolomide. With reduced systemic exposure, these new agents
have the potential to improve efficacy and therapeutic index in the treatment of
glioblastoma.
PMID- 27614415
TI - Influence of Dentoalveolar Ankylosis on the Biomechanical Response of a Single
rooted Tooth and Surrounding Alveolar Bone: A 3-dimensional Finite Element
Analysis.
AB - INTRODUCTION: Dentoalveolar ankylosis necessarily accompanies the loss of
periodontal ligament (PDL), which might alter the biomechanical response of the
tooth. The purpose of this study was to investigate the influence of
dentoalveolar ankylosis on a single-rooted tooth and the surrounding alveolar
bone structures in the biomechanical standpoint. METHODS: A basic model of an
intact maxillary central incisor and the surrounding bone structures was chosen
for the numeric analysis. From this basic model, 6 different models were further
developed by combining 3 types of endodontic status (an intact model, a
nonsurgically treated model, and a surgically treated model) and 2 types of
periodontal attachment condition (models with or without PDL). For each
condition, maximum von Mises stress (sigma max) in dentin and bone and maximum
tooth displacement (DeltaR max) were calculated. RESULTS: In models with
dentoalveolar ankylosis, stress was concentrated on the cervical dentin around
the cementoenamel junction and the alveolar bone crest, whereas the stress was
more evenly distributed along the entire length of the root in models with normal
PDL. The models with dentoalveolar ankylosis showed higher stress values in
dentin (44.72%-80.56% of sigma max increase) and bone (24.23%-80.68% of sigma max
increase) and lower tooth displacement (59.22%-63.97% of DeltaR max decrease)
compared with the models with normal PDL. CONCLUSIONS: Dentoalveolar ankylosis
exerts significant changes on the biomechanical response of a single-rooted tooth
and the surrounding bone structures. The dentoalveolar complex with ankylosis
showed characteristic stress concentrations, increased stress values, and
decreased tooth displacement compared with that with normal PDL.
PMID- 27614417
TI - External radiation is associated with limited improvement in overall survival in
resected margin-negative stage IIB pancreatic adenocarcinoma.
AB - BACKGROUND: The absolute benefit of adjuvant external beam radiation therapy
after a margin-negative resection in early stage pancreatic cancer has not been
determined. METHODS: We queried the National Cancer Data Base for patients with
pathologic stage I-II pancreatic adenocarcinoma who underwent operative resection
between 2004 and 2012. Multivariate Cox regression adjusted for age, race,
comorbidities, facility type, location and volume, type of pancreatectomy, and
tumor grade was used to estimate stage-specific survival. RESULTS: A total of
15,966 patients with stage I-II pancreatic adenocarcinoma underwent upfront
operative therapy (no neoadjuvant treatment) and had a margin-negative resection
during the study period. A total of 835 (5.2%) patients were pathologic stage IA,
1,539 (9.5%) were stage IB, 3,378 (20.9%) were stage IIA, and 10,214 (63.1%) were
stage IIB. Chemoradiation utilization increased with increasing stage (22.8% in
stage IA vs 39.6% in stage IIB, P < .01). Chemoradiation was more common at low
volume centers (39.0% vs 31.7% at high-volume centers, P < .01) and with younger
age (43.3% of patients <70 years old compared to 25.0% >=70 years old, P < .01).
Treatment at a high-volume center was associated with decreased mortality (hazard
ratio 0.80-0.89) across all stages. Age >=70 years old (hazard ratio 1.18-1.29, P
< .01) and higher grade (hazard ratio 1.68-2.69, P < .01) were associated with
higher risk of mortality at all stages. Chemoradiation was associated with a
benefit in median overall survival over chemotherapy alone for stage IIB disease
(21.8 months vs 19.5 months, P < .01). Chemoradiation was not associated with a
significant benefit in median overall survival for stage IA, IB, or IIA disease
(P > .30). CONCLUSION: Addition of radiation to adjuvant chemotherapy after
margin-negative resection of pancreatic adenocarcinoma is associated with a
limited survival benefit in patients with pathologic stage IIB disease and should
be weighed against its associated risks in these patient groups.
PMID- 27614416
TI - Comparative analysis between a bipolar vessel sealing and cutting device and the
tie and suture technique in thyroidectomy: A randomized clinical trial.
AB - BACKGROUND: Advanced bipolar and ultrasonic devices have shown significant
reduction in the surgical time of thyroid operations. This randomized, controlled
trial assessed if operative time and other relevant outcomes are different for
thyroidectomies performed either with a second-generation advanced bipolar device
or traditional tie and suture technique. METHODS: Forty-one patients were
randomized into 2 groups (advanced bipolar device and traditional tie and
suture). Secondary end points included estimated blood loss, postoperative
hemorrhage or hematoma requiring operative reintervention, recurrent laryngeal
nerve injury, hypoparathyroidism, pain intensity, number of ligatures, analgesia
usage, and loss of signal during recurrent laryngeal nerve monitoring. RESULTS:
Preoperative characteristics were similar between both groups. Mean operative
time in the advanced bipolar device group was reduced by 32.5 minutes compared
with the traditional tie and suture group (P = .006). Intraoperative blood loss
was similar in both groups. Four patients presented postoperative vocal cord
dysmotility, 3 in the traditional tie and suture group and 1 in the advanced
bipolar device group (P = ns). Two of these 4 patients also had a >50% amplitude
decrease during continuous intraoperative neuromonitoring, 1 in each group. Pain
intensity, 12 hours after operation, was significantly greater in the traditional
tie and suture group (P = .015), even though pain medication requirements during
the initial 24 hours after operation were similar between groups (P = .97). There
were no cases of postoperative hemorrhage or hematoma requiring reintervention.
Postoperative, symptomatic hypocalcemia occurred in 6 patients, 4 in the
traditional tie and suture, and 2 in the advanced bipolar device group. One of
them developed permanent hypocalcemia. CONCLUSION: The use of an advanced bipolar
device in thyroid operation reduces operative time by >30 minutes, with a similar
postoperative outcome profile when compared with the traditional tie and suture
technique.
PMID- 27614418
TI - The role of computed tomography in following up pediatric skull fractures.
AB - BACKGROUND: Despite the added radiation exposure and costs, the role of computed
tomography (CT) in following pediatric skull fractures has not been fully
evaluated. METHODS: We reviewed the radiology reports and images of the initial
and follow-up head CT examinations of children with skull fractures to determine
whether any interval changes in the fracture morphology and associated
complications necessitate a change in clinical management. RESULTS: A total of
316 pediatric cases of skull fractures were identified, including 172 patients
with and 144 without follow-up scans. At follow-up, 7% of skull fractures were
unchanged, 65% healing, and 28% healed. No patient showed findings to cause a
change in clinical management or a need for further medical or surgical
intervention regardless of the number and patterns of the fractures or the
initial intracranial complications such as intracranial hemorrhage,
pneumocephalus, and traumatic brain injuries. CONCLUSIONS: Head CT may be
unnecessary in following pediatric skull fractures in asymptomatic patients to
avoid added radiation exposure and cost.
PMID- 27614419
TI - GC-ECNICI-MS analysis of S-nitrosothiols and nitroprusside after treatment with
aqueous sulphide (S2-) and derivatization with pentafluorobenzyl bromide:
Evidence of S-transnitrosylation and formation of nitrite and nitrate.
AB - A GC-MS method is reported for the quantitative analysis of S-nitrosothiols
(RSNO) derived from endogenous low- and high-molecular mass thiols (RSH)
including hemoglobin, cysteine, glutathione, N-acetylcysteine, and the exogenous
N-acetylcysteine ethyl ester. The method is based on the conversion of RSNO to
nitrite by aqueous Na2S (S2-). 15N-Labelled analogs (RS15NO) or 15N-labelled
nitrite and nitrate were used as internal standards. The nitrite (14NO2- and
15NO2-) and nitrate (O14NO2- and O15NO2- anions were derivatised by
pentafluorobenzyl (PFB) bromide (PFB-Br) in aqueous acetone and their PFB
derivatives were separated by gas chromatography. After electron-capture negative
ion chemical ionization, the anions were separated by mass spectrometry and
detected by selected-ion monitoring of m/z 46 for 14NO2-, m/z 47 for 15NO2-, m/z
62 for O14NO2-, and m/z 63 for O15NO2-. The expected thionitrites (-S14NO and
S15NO) were not detected, suggesting that they are intermediates and rapidly
exchange their S by O from water, presumably prior to PFB-Br derivatization. The
reaction of S2- with RSNO and sodium nitroprusside (SNP) resulted in the
formation of nitrite and nitrate as the major and minor reaction products,
respectively. The novel Na2S procedure was compared with established procedures
based on the use of aqueous HgCl2 or cysteine/Cu2+ reagents to convert the S
nitroso group to nitrite. Our results provide evidence for an equilibrium S
transnitrosylation reaction between S2- with RSNO in buffered solutions of
neutral pH. Use of Na2S in molar excess over RSNO shifts this reaction to the
right, thus allowing almost complete conversion of RSNO to nitrite and nitrate.
The Na2S procedure should be useful for the quantitative determination of RSNO as
nitrite and nitrate after PFB-Br derivatization and GC-MS analysis. The Na2S
procedure may also contribute to explore the complex reactions of S2- with RSNO,
SNP and other NO-containing compounds.
PMID- 27614420
TI - The Relationship of Serum Serotonin Levels to the Rate of Bone Loss and Fractures
in Men.
AB - Recent genetic studies in rodents have revealed that circulating serotonin plays
a key role in regulating bone formation and skeletal mass. However, the reported
effects of circulating serotonin on bone mass in humans have been conflicting. We
determined whether circulating serotonin levels influenced the rate of bone loss
and fractures in men. We assessed the effect of serum serotonin on bone loss rate
in a population-based cohort of 202 ambulatory men aged 56-70 years who were
followed up for a median duration of 3.7 years. Serum serotonin levels were
assayed, and the Timed Up and Go Test (TUGT) was performed, at baseline. Dual
energy X-ray absorptiometry was performed both at baseline and during follow-up.
Fracture prevalence was assessed using questionnaires. The serotonin levels were
inversely associated with the lumbar spine bone mineral density (r = -0.174, p =
0.028) at baseline. No association was evident between the bone mineral densities
of the femoral neck or total hip and serotonin level. The annual rates of bone
loss from the lumbar spine, the femoral neck, and the total hip were 0.01%,
0.46%, and 0.46%, respectively. The baseline serum serotonin level did not
predict the bone loss rate in any skeletal site. Lower limb disability evident
upon TUGT at baseline predicted bone loss from the total hip. No significant
difference of serotonin level was observed between subjects with and without
fractures. The serum serotonin level was not associated with the rate of bone
loss in elderly men. Thus, the circulating serotonin level does not reliably
predict bone loss.
PMID- 27614422
TI - Staphylococci isolated from ready-to-eat meat - Identification, antibiotic
resistance and toxin gene profile.
AB - The aim of this study was to analyse the staphylococci isolated from ready-to-eat
meat products, including pork ham, chicken cold cuts, pork sausage, salami and
pork luncheon meat, sliced in the store to the consumer's specifications, along
with species identification and determination of antibiotic resistance. Genes
encoding staphylococcal enterotoxins, staphylococcal enterotoxin-like proteins,
exfoliative toxins, and toxic shock syndrome toxin 1 were also investigated. From
the 41 samples, 75 different staphylococcal isolates were obtained. Based on PCR
RFLP analysis of the gap gene using AluI and HpyCH4V restriction enzymes, the
isolates were identified as Staphylococcus equorum (28%), S. vitulinus (16%), S.
carnosus (14%), S. succinus (11%), S. xylosus (11%), S. saprophyticus (9%), S.
warneri (9%), S. haemolyticus (1%) and S. pasteuri (1%). The incidence and number
of resistances to antimicrobials was found to be species but not source of
isolation dependent. All S. xylosus, S. saprophyticus, S. haemolyticus and S.
pasteuri isolates showed antibiotic resistance. A lower percentage of resistance
was recorded for S. warneri (71%) and S. vitulinus (58%), followed by S. equorum
(57%), S. carnosus (50%) and S. succinus (50%). The most frequent resistance was
observed to fusidic acid (43%). The mecA gene was amplified in 4% of the
staphylococci. However, phenotypic resistance to methicillin was not confirmed in
any of these isolates. On the other hand, the mecA gene was not detected in any
of 9% of the isolates resistant to cefoxitin. It was also found that among 75
isolates, 60 (80%) harbored from 1 to 10 out of 21 analyzed superantigenic toxin
genes. The most prevalent genes were: sei (36% isolates) among enterotoxins, seln
(32% isolates) among enterotoxin-like proteins and eta encoding exfoliative toxin
A (37% isolates). The findings of this study further extend previous observations
that, when present in food, not only S. aureus but also other species of
staphylococci could be of public health significance.
PMID- 27614421
TI - The Use of the Fracture Risk Assessment (FRAX(r)) Tool in Predicting Risk of
Fractures in Patients With Inflammatory Bowel Disease: A Systematic Review.
AB - Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative
colitis, is associated with an increased prevalence of osteoporosis and
osteopenia. We aim to evaluate the use of the World Health Organization Fracture
Risk Assessment (FRAX(r)) tool in these patients to assess 10-yr risk of
fracture. Electronic searches were performed with key words relating to IBD and
FRAX in the MEDLINE, EMBASE, and SCOPUS databases. Summary estimates were
calculated. A fixed or random-effects model was used depending on heterogeneity
(I2). The search yielded 146 references; 7 that included research carried out in
adult patients, were used in the systematic review and quantitative summary. No
significant publication bias was noted according to the Harbord test. The 10-yr
probability of hip and major osteoporotic fracture in adult IBD patients was
1.03% (95% confidence interval [CI]: 0.37%-2%; I2 = 0%) and 4.05% (95% CI: 2.61%
5.79%; I2 = 49%), respectively. In those patients with Crohn's disease, hip and
major osteoporotic fractures calculated with FRAX increased to 1.74% (95% CI:
0.42%-3.93%; I2 = 37.5%) and 6.65% (95% CI: 2.97%-11.66%; I2 = 8.7%),
respectively. Risks of fracture in adults with ulcerative colitis were provided
by a single study only. The FRAX tool has been limitedly used in patients with
IBD; however, the evidence currently available only shows a modest increase in
the 10-yr risks of bone fracture and does not support unequivocally the need for
specific interventions. Further well-designed studies are needed to confirm the
results obtained from this systematic review.
PMID- 27614423
TI - Distribution of tannin-'tolerant yeasts isolated from Miang, a traditional
fermented tea leaf (Camellia sinensis var. assamica) in northern Thailand.
AB - Miang is a fermented food product prepared from the tea leaves of Camellia
sinensis var. assamica, and is traditionally produced in mountainous areas of
northern Thailand. Although Miang has a long history and reveals deep-rooted
cultural involvement with local people in northern Thailand, little is known
regarding its microbial diversity. Yeasts were isolated from 47 Miang samples
collected from 28 sampling sites, including eight provinces in upper northern
Thailand. A hundred and seven yeast isolates were recovered and identified within
14 species based on the comparison of the D1/D2 sequence of the large subunit
(LSU) rRNA gene. Candida ethanolica was determined to be the dominant species
that was frequently found in Miang together with minor resident yeast species.
All yeast isolates demonstrated their tannin-tolerant capability when cultivated
on yeast malt agar (YMA) containing 50g/l tannin, but nine isolates displayed
clear zones forming around their colonies, e.g., Debaryomyces hansenii,
Cyberlindnera rhodanensis, and Sporidiobolus ruineniae. The results obtained from
a visual reading method of tannase revealed that all yeast isolates were positive
for methyl gallate, indicating that they possess tannase activity. It is assumed
that a tannin-tolerant ability is one of the most important factors for
developing a yeast community in Miang. This research study is the first report to
describe tannin-tolerant yeasts and yeast communities in traditionally fermented
tea leaves.
PMID- 27614424
TI - Characteristics, incidence and outcome of patients admitted to intensive care
because of pulmonary embolism.
AB - BACKGROUND AND OBJECTIVE: Despite the clinical significance of major pulmonary
embolism (PE), little is known about patients with a presentation severe enough
to lead to intensive care unit (ICU) admission and nothing is known about PE
requiring mechanical ventilation (MV). We aimed to examine the characteristics,
incidence and outcome of patients with PE as their reason for ICU admission.
METHODS: We performed a retrospective, cross-sectional study of patients admitted
to Australia's and New Zealand's ICUs because of PE from 2005 to 2013. We
compared survivors with non-survivors and mechanically ventilated with non
ventilated patients. We analysed variations in incidence and mortality over time.
RESULTS: We studied 2797 patients. PE accounted for 0.3% of all ICU admissions
and had a population incidence of 11 cases/million people/year, which increased
significantly during the study period (P < 0.0001). Co-morbidities were common
(24.1%) and the emergency department was the most common admission source
(49.1%). However, patients who died were more commonly admitted from the wards (P
< 0.0001). Overall mortality was 14.1% but reached 41.0% in patients requiring MV
(P < 0.0001). Illness severity-adjusted mortality rate did not change during the
study period. CONCLUSION: The incidence of PE requiring admission to ICU has
increased over time; its mortality rate remains high, especially in mechanically
ventilated patients, and its prognosis has not improved over time. Our findings
imply the need for focused research in this high-risk patient group.
PMID- 27614425
TI - Do Coinfections Maintain Genetic Variation in Parasites?
AB - Host individuals are often infected with multiple, potentially interacting
parasite species and genotypes. Such coinfections have consequences for
epidemiology, disease severity, and evolution of parasite virulence. As fitness
effects of coinfection can be specific to interacting parasite genotypes,
coinfections may induce high fitness variation among parasite genotypes. We argue
that such interactions can be an important mechanism maintaining genetic
variation in parasite traits such as infectivity and virulence. We also argue
that such interactions may slow coevolutionary dynamics between hosts and
parasites. This is because, instead of depending only on host genotype, parasite
fitness may be determined by average infection success across all coinfection
scenarios.
PMID- 27614426
TI - What Type of Awareness Does Binocular Rivalry Assess?
AB - Recent experiments demonstrate that invisible stimulus features can induce
binocular rivalry, indicating the phenomenon may be caused by differences in
perceptual signal strength rather than conscious selection processes. Here, we
clarify binocular rivalry's role in consciousness research by highlighting a
critical difference between two distinct types of visual awareness.
PMID- 27614427
TI - Epidemiological characterization of Acinetobacter baumannii bloodstream isolates
from a Chinese Burn Institute: A three-year study.
AB - Acinetobacter baumannii infection is a serious threat to burn patients.
Bacteremia due to A. baumannii is becoming the most common cause of mortality
following burn. However, the epidemiology of A. baumannii causing burn-related
bloodstream infections has rarely been reported. We retrospectively collected 81
A. baumannii isolates from the bloodstream of burn patients over a three-year
period. Antibiotic susceptibility tests, the prevalence of antibiotic-resistant
genes and sequence typing (ST) were conducted to characterize these strains. Most
of the isolates showed an extensive drug-resistant phenotype. The resistance
frequencies to imipenem and meropenem were 94% and 91%, respectively. The blaOXA
23-like gene, AmpC, IS-AmpC, PER and SIM are the five most prevalent resistant
genes, and their prevalence rates are 93% (75/81), 86% (70/81), 73% (59/81), 73%
(59/81) and 52% (42/81), respectively. The 81 isolates were grouped into 10 known
and 18 unknown ST types, with ST368 (38%) being the most prevalent. Except for
ST457 and four new types (STn2, STn6, STn11 and STn14), the remaining 23 ST types
belonged to one clonal complex 92, which is most common among clinical isolate in
China. The above results indicated that ST368 isolates possessing both the blaOXA
23-like gene and ampC gene were the main culprits of the increasing nosocomial A.
baumannii infection in this study. More attention should be paid to monitoring
the molecular epidemiology of A. baumannii isolates from burn patients to prevent
further distribution. Such information may help clinicians with therapeutic
decisions and infection control in the Burns Institute.
PMID- 27614428
TI - Regulatory T cells function at the early stage of tumor progression in a mouse
model of tongue squamous cell carcinoma.
AB - The objective of this study was to observe the distribution of regulatory T cells
(Tregs) in the development of tongue squamous cell carcinoma (SCC) and to
determine the role of Tregs in the progression of tongue SCC. A mouse model of 4
nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression
of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-beta,
chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined
using real-time quantitative polymerase chain reaction. Foxp3 expression was also
analyzed using immunohistochemistry. The results were compared with those of
control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2)
inhibitor. Well to moderately differentiated tongue SCC was induced in all of the
experimental mice. The amount of Tregs of the experimental mice was over 10 times
as much as control mice at the early stage of tumor progression. COX-2 inhibitor
did not prevent the progression of tongue SCC and did not reduce the total amount
of Tregs. Tregs function at the early stage of the development of tongue SCC, and
it may be effective to suppress Tregs at the early stage of tumor progression for
the treatment and/or prevention of tongue SCC.
PMID- 27614429
TI - Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to
lymphoma.
AB - Histone deacetylases (HDACs) are a family of enzymes that influence expression of
genes implicated in tumor initiation, progression, and anti-tumor responses. In
addition to their canonical role in deacetylation of histones, HDACs regulate
many non-canonical targets, such as Signal Transducer and Activator of
Transcription 3 (STAT3). We hypothesize that tumors use epigenetic mechanisms to
dysregulate CD1d-mediated antigen presentation, thereby impairing the ability of
natural killer T (NKT) cells to recognize and destroy malignant cells. In this
study, we pre-treated CD1d-expressing tumor cells with HDAC inhibitors (HDACi)
and assessed CD1d-dependent NKT cell responses to mantle cell lymphoma (MCL). Pre
treatment with Trichostatin-A, a pan-HDACi, rapidly enhanced both CD1d- and MHC
class II-mediated antigen presentation. Similarly, treatment of MCL cells with
other HDACi resulted in enhanced CD1d-dependent NKT cell responses. The observed
changes are due, at least in part, to an increase in both CD1D mRNA and CD1d cell
surface expression. Mechanistically, we found that HDAC2 binds to the CD1D
promoter. Knockdown of HDAC2 in tumor cells resulted in a significant increase in
CD1d-mediated antigen presentation. In addition, treatment with HDACi inhibited
STAT3 and STAT3-regulated inflammatory cytokine secretion by MCL cells. We
demonstrated that MCL-secreted IL-10 inhibits CD1d-mediated antigen presentation
and pre-treatment with TSA abrogates secretion of IL-10 by MCL. Taken together,
our studies demonstrate the efficacy of HDACi in restoring anti-tumor responses
to MCL through both cell-intrinsic and cell-extrinsic mechanisms and strongly
implicate a role for HDACi in enhancing immune responses to cancer.
PMID- 27614430
TI - Bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate inhibit cell
proliferation via ROS-induced sustained MAPK/ERK activation but with elevated AKT
activity in human pancreatic cancer AsPC-1 cells.
AB - In this study, the antiproliferative effect of bis(acetylacetonato)
oxidovanadium(IV) and sodium metavanadate and the underlying mechanisms were
investigated in human pancreatic cancer cell line AsPC-1. The results showed that
both exhibited an antiproliferative effect through inducing G2/M cell cycle
arrest and can also cause elevation of reactive oxygen species (ROS) levels in
cells. Moreover, the two vanadium compounds induced the activation of both
PI3K/AKT and MAPK/ERK signaling pathways dose- and time-dependently, which could
be counteracted with the antioxidant N-acetylcysteine. In the presence of MEK-1
inhibitor, the degradation of Cdc25C, inactivation of Cdc2 and accumulation of
p21 were relieved. However, the treatment of AKT inhibitor did not cause any
significant effect. Therefore, it demonstrated that the ROS-induced sustained
MAPK/ERK activation rather than AKT contributed to vanadium compounds-induced
G2/M cell cycle arrest. The current results also exhibited that the two vanadium
compounds did not induce a sustained increase of ROS generation, but the level of
ROS reached a plateau instead. The results revealed that an intracellular
feedback loop may be against the elevated ROS level induced by vanadate or
VO(acac)2, evidenced by the increased GSH content, the unchanged level at the
expression of antioxidant enzymes. Therefore, vanadium compounds can be regarded
as a novel type of anticancer drugs through the prolonged activation of MAPK/ERK
pathway but retained AKT activity. The present results provided a proof-of
concept evidence that vanadium-based compounds may have the potential as both
antidiabetic and antipancreatic cancer agents to prevent or treat patients
suffering from both diseases.
PMID- 27614431
TI - RNA-seq analysis of the transcriptional response to blue and red light in the
extremophilic red alga, Cyanidioschyzon merolae.
AB - Light is one of the main environmental cues that affects the physiology and
behavior of many organisms. The effect of light on genome-wide transcriptional
regulation has been well-studied in green algae and plants, but not in red algae.
Cyanidioschyzon merolae is used as a model red algae, and is suitable for studies
on transcriptomics because of its compact genome with a relatively small number
of genes. In addition, complete genome sequences of the nucleus, mitochondrion,
and chloroplast of this organism have been determined. Together, these attributes
make C. merolae an ideal model organism to study the response to light stimuli at
the transcriptional and the systems biology levels. Previous studies have shown
that light significantly affects cell signaling in this organism, but there are
no reports on its blue light- and red light-mediated transcriptional responses.
We investigated the direct effects of blue and red light at the transcriptional
level using RNA-seq. Blue and red lights were found to regulate 35 % of the total
genes in C. merolae. Blue light affected the transcription of genes involved in
protein synthesis while red light specifically regulated the transcription of
genes involved in photosynthesis and DNA repair. Blue or red light regulated
genes involved in carbon metabolism and pigment biosynthesis. Overall, our data
showed that red and blue light regulate the majority of the cellular, cell
division, and repair processes in C. merolae.
PMID- 27614433
TI - HDAC5 Inhibits Hepatic Lipogenic Genes Expression by Attenuating the
Transcriptional Activity of Liver X Receptor.
AB - BACKGROUND/AIMS: Liver X receptor (LXR), a member of the nuclear receptor
superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master
regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown
to play critical roles in glucose and lipids metabolism. However, the exact role
of HDAC5 in lipogenesis remains elusive. METHODS: mRNA and protein levels of
HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat
diet-induced and leptin receptor deficiency-induced obese mice. HDAC5 was
overexpressed or depleted in HepG2 cells, followed by analysis of cellular
triglycerides contents. Quantitative real-time PCR was used to detect the
expression levels of lipogenic genes. Luciferase reporter assay was used to
determine the regulation of HDAC on the transcriptional activity of LXR. Co
immunoprecipitation experiment was used to determine the interaction between
HDAC5 and LXR. RESULTS: We found that mRNA and protein expression levels of
hepatic HDAC5 were reduced in high-fat-diet-induced and leptin receptor
deficiency-induced obese mice. In vitro studies further demonstrated that
knockdown of HDAC5 promoted cellular triglycerides accumulation, accompanied with
up-regulation of lipogenic genes. At the molecular level, HDAC5 was shown to
interact with LXR, thereby attenuating its transcriptional activity. CONCLUSION:
Overall, our data suggest that hepatic HDAC5 is an important regulator of
lipogenesis.
PMID- 27614432
TI - Extensive transcriptomic studies on the roles played by abscisic acid and auxins
in the development and ripening of strawberry fruits.
AB - Strawberry is an ideal model for studying the molecular biology of the
development and ripening of non-climacteric fruits. Hormonal regulation of gene
expression along all these processes in strawberries is still to be fully
elucidated. Although auxins and ABA have been pointed out as the major regulatory
hormones, few high-throughput analyses have been carried out to date. The role
for ethylene and gibberellins as regulatory hormones during the development and
ripening of the strawberry fruit remain still elusive. By using a custom-made and
high-quality oligo microarray platform done with over 32,000 probes including all
of the genes actually described in the strawberry genome, we have analysed the
expression of genes during the development and ripening in the receptacles of
these fruits. We classify these genes into two major groups depending upon their
temporal and developmental expression. First group are genes induced during the
initial development stages. The second group encompasses genes induced during the
final maturation and ripening processes. Each of these two groups has been also
divided into four sub-groups according their pattern of hormonal regulation. By
analyzing gene expression, we clearly show that auxins and ABA are the main and
key hormones that combined or independently are responsible of the development
and ripening process. Auxins are responsible for the receptacle fruit development
and, at the same time prevent ripening by repressing crucial genes. ABA
regulates the expression of the vast majority of genes involved in the ripening.
The main genes expressed under the control of these hormones are presented and
their physiological rule discussed. We also conclude that ethylene and
gibberellins do not seem to play a prominent role during these processes.
PMID- 27614434
TI - Conditioned media from differentiating craniofacial bone marrow stromal cells
influence mineralization and proliferation in periodontal ligament stem cells.
AB - Previous reports have mainly focused on the behavioral responses of human
periodontal ligament stem cells (hPDLSCs) in interaction with tibia bone marrow
stromal cells (BMSCs). However, there is little study on the biologic features of
hPDLSCs under the induction of maxilla BMSCs (M-BMSCs) at different phases of
osteogenic differentiation. We hypothesized that M-BMSCs undergoing osteogenic
differentiation acted on the proliferation, differentiation, and bone-forming
capacity of hPDLSCs. In this paper, primary hPDLSCs and human M-BMSCs (hM-BMSCs)
were expanded in vitro. After screening of surface markers for characterization,
hPDLSCs were cocultured with different phases of differentiating hM-BMSCs. Cell
proliferation and alkaline phosphatase activity were examined, and mineralization
associated markers such as osteocalcin and runt-related transcription factor 2 of
hPDLSCs in coculture with uninduced/osteoinduced hM-BMSCs were evaluated. hPDLSCs
in hM-BMSCs-conditioned medium (hM-BMSCs-CM) group showed a reduction in
proliferation compared with untreated hPDLSCs, while osteoinduced hM-BMSCs for 10
day-conditioned medium (hM-BMSCs-CM-10ds) and osteoinduced hM-BMSCs for 15 day
conditioned medium (hM-BMSCs-CM-15ds) enhance the proliferation of hPDLSCs. hM
BMSCs of separate differentiation stages temporarily inhibited osteogenesis of
hPDLSCs in the early days. Upon extending time periods, uninduced/osteoinduced hM
BMSCs markedly enhanced osteogenesis of hPDLSCs to different degrees. The
transplantation results showed hM-BMSCs-CM-15ds treatment promoted tissue
regeneration to generate cementum/periodontal ligament-like structure
characterized by hard-tissue formation. This research supported the notion that
hM-BMSCs triggered osteogenesis of hPDLSCs suggesting important implications for
periodontal engineering.
PMID- 27614435
TI - Simple classification of carotid bifurcation: is it possible to predict twisted
carotid artery during carotid endarterectomy?
AB - BACKGROUND: The internal carotid artery (ICA) usually runs posterolaterally to
the external carotid artery (ECA), but occasionally we encounter the twisted
carotid bifurcation, a variant in which the ICA courses medially to the ECA
during carotid endarterectomy (CEA). Prediction of this anomaly in the
preoperative evaluation is mandatory, although descriptions in the literature are
limited. We reviewed the clinical features of patients who underwent CEA and
analyzed preoperative cerebral angiography, especially the anteroposterior (AP)
view to determine whether it could be a predictive modality. METHODS: In 58
consecutive CEA cases, we simply classified them into three groups; type 1 (the
ICA runs laterally and the ECA runs medially), type 2 (the ICA and ECA run to
overlap each other), and type 3 (the ICA runs medially and the ECA runs
laterally), based on the findings of AP view of cerebral angiography. We compared
the clinical features and intraoperative findings of these groups. RESULTS: Of 58
cases, types 1-3 were 24, 30, and four cases, respectively. Twisted carotid
bifurcations were recognized in seven cases (12.4 %), including three cases in
type 2 and four in type 3, and all twisted cases were found on the right side.
Twisted carotids and right-sided lesion were significantly frequent in type 3,
but no statistical differences of coexisting diseases were recognized among the
three groups. CEAs of twisted carotid bifurcations were performed successfully
with correction of the carotid position in three and as it was in four cases.
CONCLUSIONS: Twisted carotid bifurcations were observed during operation in 10 %
in type 2 and 100 % in type 3. CEA of twisted carotid bifurcations can be
performed safely with or without correction of the carotid position. AP view of
cerebral angiography could be useful for preoperative evaluation.
PMID- 27614436
TI - Levosimendan, a new therapeutic approach to prevent delayed cerebral vasospasm
after subarachnoid hemorrhage?
AB - BACKGROUND: Under physiological cerebral conditions, levosimendan, a calcium
channel sensitizer, has a dose-dependent antagonistic effect on prostaglandin
F2alpha (PGF)-induced vasoconstriction. This circumstance could be used in
antagonizing delayed cerebral vasospasm (dCVS), one of the main complications
after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and
ischemic neurological deficits. Data already exist that identified
neuroprotective effects of levosimendan in a traumatic brain injury model and
additionally, it has been proven that this compound prevents narrowing of the
basilar artery (BA) luminal area after SAH in an in vitro rabbit model. Takotsubo
cardiomyopathy, a severe ventricular dysfunction, is also a well-known
complication after SAH, associated with pulmonary edema and prolonged intubation.
METHODS: The polypeptide endothelin-1 (ET-1) plays a key role in the development
of dCVS after SAH. Therefore, the aim of the present investigation was to detect
functional interactions between the calcium-sensitizing and the ET-1-dependent
vasoconstriction after experimental-induced SAH; interactions between
levosimendan and a substrate-specific vasorelaxation in the BA were also
examined. It was reviewed whether levosimendan has a beneficial influence on
endothelin(A) and/or endothelin(B1) receptors (ET-(A) and ET-(B1) receptors) in
cerebral vessels after SAH. We also examined whether this drug could have
antagonistic effects on a PGF-induced vasoconstriction. RESULTS: Under treatment
with levosimendan after SAH, the endothelin system seems to be affected. The ET-1
induced contraction is decreased, not significantly. In addition, we detected
changes in the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway.
Preincubation with levosimendan causes a modulatory effect on the ET-(B1)
receptor-dependent vasorelaxation. It induces an upregulation of the NO-cGMP
pathway with a significantly increased relaxation. Even after PGF-induced
precontraction a dose-dependent relaxation was registered, which was
significantly higher (Emax) and earlier (pD2) compared to the concentration
effect curve without levosimendan. CONCLUSIONS: After experimental-induced dCVS,
levosimendan seems to restore the well-known impaired function of the
vasorelaxant ET-(B1) receptor. Levosimendan also reversed the PGF-induced
contraction dose-dependently. Both of these mechanisms could be used for
antagonizing dCVS in patients suffering SAH. Levosimendan could even be used
additionally in treating patients developing takotsubo cardiomyopathy.
PMID- 27614437
TI - Surgical anatomy of the cavernous sinus, superior orbital fissure, and orbital
apex via a lateral orbitotomy approach: a cadaveric anatomical study.
AB - BACKGROUND: Tumors of the middle fossa or cavernous sinus (CS), or intraorbital
tumors, can penetrate each other through the superior orbital fissure (SOF) or
neighboring tissue. These complicated pathologies are often treated with highly
invasive surgical procedures. In this article, we demonstrate surgical anatomic
dissections of the CS, SOF, orbital apex (OA), and dura mater extending to the
periorbita from the middle fossa, by performing an epidural dissection via a
lateral orbitotomy approach, and discuss findings that may provide guidance
during surgery in these regions. METHODS: Lateral orbitotomy was performed on
latex-injected cadaver heads by making a 2-cm skin incision lateral to the
lateral canthus, drilling the lesser and greater sphenoid wings that form the SOF
borders, and removing the bone section between the middle fossa and orbit. Dura
mater from the middle fossa to the periorbita was exposed to perform anterior
clinoidectomy. Meningeal dura was dissected from the endosteal dura, which forms
the lateral wall of the CS, to expose the CS, SOF, and OA for dissections.
RESULTS: Changing the orientation of the microscope from posterior to anterior
enabled regional control for dissection from the Gasserian ganglion to the OA.
Cranial nerves that pass through the CS, SOF, and OA were dissected and exposed.
The annular tendon was opened, revealing the oculomotor nerves and its branches,
as well as the abducens and nasociliary nerves, which pass through the oculomotor
foramen and course within the OA and orbit. CONCLUSIONS: This approach causes
less tissue damage; provides control of the surgical area in spheno-orbital
tumors invading the fissure and foramen by changing the orientation of the
microscope toward the orbit, OA, SOF, CS, and middle fossa; and expands the
indication criteria for lateral orbitotomy surgery. This approach, therefore,
represents an alternative surgical method for excising complicated tumors in
these regions.
PMID- 27614438
TI - Spontaneous resorption of giant serpentine aneurysm arising from middle cerebral
artery.
PMID- 27614439
TI - Spinal cord stimulation during the antepartum and intrapartum periods: a case
report showing no deleterious effect of conventional paraesthesia producing
stimulation.
AB - We report on a 25-year-old woman who used her spinal cord stimulator (SCS),
previously inserted for chronic regional pain syndrome (CPRS), to assist with
both chronic and pregnancy-related pain management. We describe the therapeutic
effect of the stimulator and briefly highlight the issues surrounding the use of
SCS during pregnancy.
PMID- 27614440
TI - Cardiac-Specific Overexpression of miR-222 Induces Heart Failure and Inhibits
Autophagy in Mice.
AB - BACKGROUND: MicroRNAs play a crucial role in the regulation of pathological
cardiac remodeling and heart failure. Previously, we found that overexpression of
miR-221 induces heart failure in mice. The miR-222 and miR-221 share the same
gene cluster, however, the role of miR-222 in the regulation of cardiac function
remained ill-defined. METHODS AND RESULTS: Transgenic mice with cardiac-specific
expression of miR-222 (Tg-miR-222) mice were generated. The Tg-miR-222 mice
developed significantly enlarged hearts at 4 weeks of age. Transthoracic
echocardiograph data indicated that the hearts of Tg-miR-222 mice exhibited an
increased left ventricular end-diastolic internal diameter and decreased
fractional shortening. We observed that the LC3-II in Tg-miR-222 mice was
decreased accompanied with the upregulation of p62, indicating the autophagy
inhibition in the hearts of Tg-miR-222 mice. The mTOR pathway, a negative
regulator of autophagy, was activated in the hearts of Tg-miR-222 mice. The
expression of p27 was downregulated by miR-222 overexpression. CONCLUSION: Our
data indicate that miR-222 overexpression induces heart failure in mice. The
downregulation of p27 and the activation of mTOR pathway may be involved in miR
222-induced heart failure and autophagy inhibition. Thus, targeting miR-222
expression may be a therapeutic strategy against pathological cardiac remodeling.
PMID- 27614441
TI - The convergent validity of Actiwatch 2 and ActiGraph Link accelerometers in
measuring total sleeping period, wake after sleep onset, and sleep efficiency in
free-living condition.
AB - PURPOSE: Physical activity (PA) and sleep are important to health; thus, it is
important for researchers to have valid tools to measure them. Accelerometers
have been proven valid for measuring PA and sleep, but only one device does this
simultaneously: the ActiGraph Link (ActiGraph, LLC); however, the sleep
monitoring function has not been validated. This study aimed to evaluate the
predictive power of ActiGraph Link sleep parameters against a validated
accelerometer (Actiwatch 2, Phillips Respironics Mini-Mitter). METHODS: A total
of 49 Hong Kong adults aged 18-64 provided valid data on both accelerometers on
their non-dominant wrist for seven consecutive days. Epochs from both
accelerometers were classified as either sleep or awake using seven established
algorithms (Cole-Kripke, Sadeh, Sazonov, high sensitivity threshold, medium
sensitivity threshold, low sensitivity threshold, and neural network model), and
these data were transformed to total sleeping period, wake after sleep onset, and
sleep efficiency. RESULTS: The non-zero count data for both accelerometers
(331,103 observations) were strongly correlated with a Spearman correlation of
0.83 (p < 0.001). The total sleeping period was highly correlated (Spearman
correlation ranged from 0.74 to 0.90) regardless of the algorithms used. All
algorithms yielded insignificant difference in total sleep time measured by the
two accelerometers (p > 0.05) with a negligible effect size of d < 0.2. The
agreement of sleep/wake status was high for all algorithms, with accuracy ranging
from 93.05 % (Sadeh's algorithm) to 96.13 % (Cole-Kripke's algorithm).
CONCLUSIONS: Results showed that the sleep function of the ActiGraph Link
performs similar to a validated accelerometer (Actiwatch 2) and provides an
opportunity to measure both sleep and PA simultaneously.
PMID- 27614442
TI - Aging asymmetry: systematic survey of changes in age-related biomarkers in the
annual fish Nothobranchius guentheri.
AB - Aging asymmetry is the observation that different tissues age in different ways
and at different rates. This has not been assessed in a single organism using
multiple biomarkers of aging. Here we clearly demonstrated that the levels of
protein oxidation and lipid peroxidation as well as CAT, SOD and GPX activities
all showed a tissue-dependent change with advancing age; and DNA repair ability,
as revealed by the expression of ercc1 and its protein levels, also exhibited a
tissue-specific variation with age. We also found that protein oxidation and
lipid peroxidation levels remained relatively stable in the liver, intestine,
skin and testis as well as in the brain, eye and heart of young, adult and aged
fishes; SOD and GPX activities displayed little variation in the intestine, eye
and skin as well as in the brain and skin of young, adult and aged fishes; and
low and stable expression of ercc1 was observed in the spleen, eye and heart of
young, adult and aged fishes. Collectively, these results indicate that aging is
tissue specific and asymmetric in N. guentheri. The observation of aging
asymmetry may have practical implications for the application of non-intrusion
intervention approaches to prolong lifespan.
PMID- 27614443
TI - Quantitative Assessment of Surgical Anatomy and Three-Dimensional Relationships
in the Supralabyrinthine Space.
AB - OBJECTIVE: To explore and quantify the surgically relevant anatomic relationships
and three-dimensional (3D) morphology of the supralabyrinthine space, and enable
a deeper, clearer understanding of its regional anatomy. MATERIALS AND METHODS:
3D-DOCTOR software was used to create a 3D reconstruction of the axial CT images
and multiplanar reformatting of 55 slices of temporal bone in 29 patients (17
males and 12 females), whose average age was 38.69 +/- 17.81 years. The 3D
relationships between the mutual complex structures were displayed graphically
and measured. RESULTS: The important structures within the temporal bone were
displayed in detail. 3D relationships between the structures in the temporal
bone, such as the ossicles, facial nerves, labyrinth, and skull base, were
quantified. CONCLUSION: Quantification of surgically relevant anatomic
relationships and the morphology of the supralabyrinthine space in three
dimensions are very helpful in surgical dissection.
PMID- 27614444
TI - Community engagement and education: addressing the needs of South Asian families
with genetic disorders.
AB - Consanguineous marriage is common among the South Asian heritage community in the
UK. While conferring social and cultural benefits, consanguinity is associated
with an increased risk of autosomal recessive disorders and an increase in
childhood death and disability. We have previously developed a genetic service to
address the needs of this community. We report the extension of this service to
include community-based initiatives aimed at promoting understanding of genetic
issues related to consanguinity and improving access to genetic services. Our
approach was to develop integrated clinical, educational and community engagement
initiatives that would be sustainable on a long-term basis. The service provided
for South Asian families by a specialist genetic counsellor was extended, and a
series of genetics education and awareness sessions were provided for a diverse
range of frontline healthcare workers. Two community genetic outreach worker
posts were established to facilitate the engagement of the local South Asian
population with genetics. The education and awareness sessions helped address the
lack of genetic knowledge among primary health care professionals and community
workers. Engagement initiatives by the genetic outreach worker raised awareness
of genetic issues in the South Asian community and families affected by autosomal
recessive disorders. All three elements of the extended service generated
positive feedback. A three-stranded approach to addressing the needs of
consanguineous families affected by autosomal recessive disorders as recommended
by the World Health Organisation is suggested to be an acceptable, effective and
sustainable approach to delivery of service in the UK.
PMID- 27614445
TI - State-of-the-Art Treatment and Novel Agents in Local and Distant Recurrences of
Cervical Cancer.
AB - Depending on the stage at initial presentation, cervical cancer will recur in 25
61% of women. Typical manifestations of recurrent cervical cancer include the
central pelvis and the pelvic side walls as well as retroperitoneal lymph node
basins in the pelvis and the para-aortic region, and - more rarely -
supraclavicular lymph nodes. There are no typical symptoms of recurrent cervical
cancer. Women with suspected recurrence after cervical cancer based on
gynecological examination or organ-specific symptoms must undergo imaging studies
and - if technically feasible - biopsy with histological verification, especially
in cases of distant metastases, in order to rule out a second primary.
Radiotherapy-naive women should be treated with salvage radiochemotherapy with
curative intention. For women with previous radiotherapy, surgery in the form of
hysterectomy, local resection, or pelvic exenteration is the treatment of choice.
Pelvic exenteration can lead to cure in selected patients, but at the price of a
high rate of complications and significant morbidity and mortality. If complete
surgical resection is not feasible or if the woman is not a candidate for
surgery, chemotherapy with palliative intent should be offered. Patients with
recurrent disease outside the pelvis are candidates for systemic chemotherapy.
Several agents have shown to be active in this situation, either in single-agent
or combination regimens. Platinum-containing regimens have a superior efficacy
over non-platinum regimens and bevacizumab may be added to chemotherapy.
PMID- 27614447
TI - A Change of Paradigm in the Treatment of Cervical Cancer.
PMID- 27614448
TI - Could CRISPR be the solution for gene editing's Gordian knot?
PMID- 27614446
TI - Preoperative vitamin C supplementation improves colorectal anastomotic healing
and biochemical parameters in malnourished rats.
AB - PURPOSES: The objective of this study was to evaluate the effect of
supplementation with vitamin C on intestinal anastomosis healing in malnourished
rats. METHODS: Male Wistar rats were divided into three groups: (1) sham, well
nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to
food restriction and received vehicle; and (3) FR+VC, rats that were subjected to
food restriction and received vitamin C. Four days before surgery, the animals
received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with
anastomosis in a single plane. The survival rate of rats was monitored until day
7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal
adhesion index, hydroxyproline content, collagen density, inflammatory
parameters, and oxidative damage to proteins and lipids. RESULTS: Malnutrition
decreases body weight and increases mortality; the survival rate was 90 % in
group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase
hydroxyproline concentration and density of collagen and decrease the intra
abdominal adhesion index, as well as the infiltration of neutrophils and
oxidative damage to proteins in malnourished rats compared to group treated with
vehicle. CONCLUSIONS: Preoperative vitamin C supplementation can improve the
intestinal anastomosis healing, biochemical alterations, and prolong survival in
rats subjected to food restriction.
PMID- 27614449
TI - Thanks for your accompanying in the journey of integrative medicine : -Strength
and confidence from the predecessors of Chinese medical association.
PMID- 27614451
TI - Effects of Shen-Fu Injection () on apoptosis of regulatory T lymphocytes in
spleen during post-resuscitation immune dysfunction in a porcine model of cardiac
arrest.
AB - OBJECTIVE: To investigate whether Shen-Fu Injection (, SFI) reduces post
resuscitation immune dysfunction in a porcine model of cardiac arrest by
modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen. METHODS:
After 8-min untreated ventricular fibrillation and 2-min basic life support, 24
pigs were divided into 3 groups with a random number table, i.e. SFI group,
epinephrine (EP) group, and saline (SA) group (8 in each group), which received
central venous injection of SFI (1.0 mL/kg), EP (0.02 mg/kg) and SA,
respectively. The same procedure without CA initiation was achieved in the sham
operated (sham) group (n=6). After successful return of spontaneous circulation
(ROSC), apoptosis rate of splenic Treg was detected by flow cytometry; and the
mRNA expression of forkhead/winged helix transcription factor (Foxp3) of splenic
Treg was detected by real time-polymerase chain reaction; and the levels of
interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in porcine splenic Treg
were detected by using enzyme-linked immunosorbent assay (ELISA). RESULTS:
Compared with the sham group, the apoptosis rate of Treg was significantly
decreased, and the levels of Foxp3 mRNA expression, IFN-gamma, IL-4 and IFN
gamma/IL-4 were increased in the SA group (P<0.05 or P<0.01). Compared with the
EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced
the levels of Foxp3 mRNA expression, IFN-gamma and IFN-gamma/IL-4 (P<0.05).
CONCLUSIONS: SFI has signifificant effects in attenuating post-resuscitation
immune dysfunction by modulating apoptosis of Treg in the spleen.
PMID- 27614450
TI - Long-term clinical effect of Tangyiping Granules () on patients with impaired
glucose tolerance.
AB - OBJECTIVE: To evaluate the long-term clinical effect of Tangyiping Granules (,
TYP) on patients with impaired glucose tolerance (IGT) to achieve normal glucose
tolerance (NGT) and hence preventing them from conversion to diabetes mellitus
(DM). METHODS: In total, 127 participants with IGT were randomly assigned to the
control (63 cases, 3 lost to follow-up) and treatment groups (64 cases, 4 lost to
follow-up) according to the random number table. The control group received
lifestyle intervention alone, while the patients in the treatment group took
orally 10 g of TYP twice daily in addition to lifestyle intervention for 12
weeks. The rates of patients achieving NGT or experiencing conversion to DM as
main outcome measure were observed at 3, 12, and 24 months after TYP treatment.
The secondary outcome measures included fasting plasma glucose (FPG), 2-h
postprandial plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting
insulin (FINS), 2-h insulin (2hINS), homeostatic model assessment of insulin
resistance (HOMA-IR), blood lipid and patients' complains of Chinese medicine
(CM) symptoms before and after treatment. RESULTS: A higher proportion of the
treatment group achieved NGT compared with the control group after 3-, 12- and 24
month follow-up (75.00% vs. 43.33%, 58.33% vs. 35.00%, 46.67% vs. 26.67%,
respectively, P<0.05). The IGT to DM conversion rate of the treatment group was
significantly lower than that of the control group at the end of 24-month follow
up (16.67% vs. 31.67%, P<0.05). Before treatment, FPG, 2hPG, HbA1c, FINS, 2hINS,
HOMA-IR, triglyceride (TG), total cholesterol, low- and high-density lipoprotein
cholesterol levels had no statistical difference between the two groups (P>0.05).
After treatment, the 2hPG, HbA1c, HOMA-IR, and TG levels of the treatment group
decreased significantly compared with those of the control group (P<0.05). CM
symptoms such as exhaustion, irritability, chest tightness and breathless,
spontaneous sweating, constipation, and dark thick and greasy tongue were
significantly improved in the treatment group as compared with the control group
(P<0.05). No severe adverse events occurred. CONCLUSION: TYP administered at the
IGT stage with a disciplined lifestyle delayed IGT developing into type 2 DM.
PMID- 27614452
TI - Non-invasive treatment to grade 1 essential hypertension by percutaneous laser
and electric pulse to acupoint with music: A randomized controlled trial.
AB - OBJECTIVE: To study a non-drug therapy for hypertension disease by combining
percutaneous laser and electric pulse stimulation to acupoint with music, and to
test the efficiency of the combining treatment to grade 1 essential hypertension.
METHODS: A total of 174 patients with grade 1 essential hypertension were
randomly assigned to 3 groups with a random number table after Chinese medicine
(CM) syndrome differentiation: the photoelectric and musical treatment group
(Group 1, with a self-developed multi-mode audio frequency pulse photoelectric
therapeutic apparatus), acupuncture group (Group 2), and oral placebo group
(Group 3), 58 cases per group. The curative effect of each group was evaluated by
the changes of blood pressure and CM syndrome integral before and after
treatment. RESULTS: Compared with Group 3, there were significant decrease of
blood pressure and CM syndrome integral in Group 1 and Group 2 (P<0.01). Compared
with Group 2, Group 1 showed the highest decrease in systolic pressure (P<0.017).
The total effective rate of anti-hypertension in Group 1 (91.38%, 53/58) was
significantly higher than that in Group 2 (74.13%, 43/58) and Group 3 (18.97%,
11/58, P<0.05 or P<0.01); and that in Group 2 was also significantly higher than
that in Group 3 (P<0.01). There were significant difference in the total
effective rate of CM syndrome integral in both Group 1 (93.10%, 54/58) and Group
2 (84.48%, 49/58) as compared with Group 3 (17.24%, 10/58, P<0.01), while there
was no significant difference between Group 1 and Group 2 (P>0.05). CONCLUSIONS:
The multi-mode audio frequency pulse photoelectric therapeutic apparatus,
combining music, laser and electric pulse stimulation, is clinically useful for
grade 1 essential hypertension. This "three in one" therapy method is non
invasive, easy and simple to handle. It is expected to be popularized as a new
alternative treatment.
PMID- 27614453
TI - The circular RNA ciRS-7 (Cdr1as) acts as a risk factor of hepatic microvascular
invasion in hepatocellular carcinoma.
AB - PURPOSE: Circular RNAs (circRNA) represent a novel class of widespread and
diverse endogenous RNAs that regulate gene expression in mammals. microRNA-7 (miR
7) is a well-demonstrated suppressor of hepatocellular carcinoma (HCC). Recent
studies have showed that one such circRNA, ciRS-7 (also termed as Cdr1as) was the
inhibitor and sponge of miR-7 in the embryonic zebrafish midbrain and islet
cells. However, the relationships among ciRS-7, miR-7 and clinical features of
HCC remain to be clarified. METHODS: Expression levels of ciRS-7, miR-7 and three
miR-7-targeted mRNAs in 108 pairs of HCC and their matched non-tumor tissues were
examined by quantitative reverse transcription polymerase chain reaction (qRT
PCR). The protein production of these three miR-7-targeted mRNAs was further
verified by Western blot. The relationship between ciRS-7 level and
clinicopathological features as well as the recurrence of HCC patients was
analyzed. The univariate and multivariate logistic regression analyses were used
to detect the risk factors of hepatic microvascular invasion (MVI). The
correlation among ciRS-7, miR-7 and miR-7-targeted mRNAs was evaluated using
Spearman's correlation test. RESULTS: There was no significant difference of ciRS
7 expression levels between the HCC tissues and the matched non-tumor tissues
(0.67 +/- 1.49 vs. 0.44 +/- 0.45, p = 0.13), and the ciRS-7 levels in more than
half of HCC tissues (65 out of 108, 60.2 %) were down-regulated when compared
with their matched non-tumor tissues. However, the expression of ciRS-7 was
significantly correlated with the following three clinicopathological
characteristics of HCC patients: age <40 years (p = 0.02), serum AFP >=400 ng/ul
(p < 0.01) and hepatic MVI (p = 0.03). Meanwhile, up-regulated ciRS-7 expression
was not only an independent risk factor of hepatic MVI but also had a capable
predictive ability for MVI (AUC = 0.68, p = 0.001) at the cut-off value of 0.135.
Furthermore, the expression of ciRS-7 in HCC tissues with concurrent MVI was
inversely correlated with that of miR-7 (r = -0.39, p = 0.007) and positively
related with that of two miR-7-targeted genes [PIK3CD (r = 0.55, p < 0.001) and
p70S6K (r = 0.34, p = 0.021)]. In addition, the median recurrent time of patients
from higher ciRS-7 level group was shorter than that of lower ciRS-7 group (18
vs. 25 months), but no significant difference was observed (p = 0.38).
CONCLUSIONS: The expression levels of ciRS-7 were comparable between HCC and
matched non-tumor tissues. However, the highly ciRS-7 expression in HCC tissues
was significantly correlated with hepatic MVI, AFP level and younger age and thus
partly related with the deterioration of HCC. Especially, ciRS-7 was one of the
independent factors of hepatic MVI. These data suggested that ciRS-7 may be a
promising biomarker of hepatic MVI and a novel therapy target for restraining
MVI.
PMID- 27614455
TI - Integrative taxonomy of the fly orchid group: insights from chemical ecology.
AB - Several authors have recently stressed the need to develop an integrative
approach in taxonomy, but studies applying such an approach to Mediterranean
orchids are scarce. In sexually deceptive orchids from the taxonomically
difficult genus Ophrys, pollination is specific and performed by male insects
attracted to the flowers by sex pheromone-mimicking floral scents. Floral
compounds are therefore of primary importance for reproductive isolation and
species delimitations in this genus. In the fly orchid group, molecular,
morphological, and ecological characters have been extensively studied, but a
comprehensive survey of floral scents is still lacking. In the present study, the
blends of floral compounds of its three members, Ophrys insectifera, Ophrys
aymoninii, and Ophrys subinsectifera, were extracted and analyzed by gas
chromatography-mass spectrometry. A total of 107 compounds were found, with a
majority of saturated and unsaturated hydrocarbons. Significant differentiation,
both qualitative and quantitative, was found among the three taxa. This result,
pooled with those from the literature, forms a comprehensive and congruent
dataset that allows us to elucidate the taxonomic rank of the three members of
the fly orchid group.
PMID- 27614454
TI - Cryopreserved NK cells in the treatment of haematological malignancies:
preclinical study.
AB - BACKGROUND: Leukaemia is an aggressive cancer of haematopoiesis. Despite
increasing treatment success, the relapse rate is still high. Natural killer (NK)
cells play a key role in the immune response to malignancies; thus, it is
conceivable that NK cell-based immunotherapy may control relapses, while
extending the disease-free survival. In our study, we investigated whether
cryopreserved NK cells are able to kill the leukaemic K562 cell line, the
necessity of IL-2 co-application and the association of activation marker
expression (NKp44, NKG2D and CD25) with cytotoxic potential. MATERIALS AND
METHODS: K562 cells were added to NK cell cultures in different ratios, i.e. 1:5,
1:10 and 1:20 (K562/NK), immediately after thawing NK cells or after 3-6-12-24 h
of re-cultivation with or without IL-2. RESULTS: Our results demonstrated the
ability of cryopreserved NK cells to kill K562 in all ratios, times and culture
conditions. The number of dead K562 cells depended on the number of NK cells and
on the presence of IL-2. NK cells cytotoxic potential decreased gradually in the
culture without IL-2. In contrast, NK cell-mediated cytotoxicity remained the
same during the entire re-culture period after IL-2 re-application. CONCLUSION:
Our study proved the efficacy of using cryopreserved ready-for-use NK cells in
relapse treatment and the need for simultaneous administration of IL-2.
PMID- 27614456
TI - Origin of origami cockroach reveals long-lasting (11 Ma) phenotype instability
following viviparity.
AB - Viviparity evolved in bacteria, plants, ?141 vertebrate lineages (ichthyosaurs,
lizards, fishes, mammals, and others), and in 11 of 44 insect orders. Live-birth
cockroaches preserved with brood sac (3D recovered two times optically) included
Diploptera vladimir, Diploptera savba, Diploptera gemini spp.n., D. sp.1-2, and
Stegoblatta irmgardgroehni from Green River, Colorado; Quilchena, Republic;
McAbee, Canada; and Baltic amber, Russia (49, 54, and 45 Ma). They evolved from
rare and newly evolved Blaberidae; they radiated circumtropically, later expanded
into SE Asia, and have now spread to Hawaii and the SE USA. Association of
autapomorphic characters that allow for passive and active protections from
parasitic insects (unique wing origami pleating identical with its egg case
attacking wasp) suggest a response to high parasitic loads. Synchronized with
global reorganization of the biota, morphotype destabilization in roaches lasted
approximately 11-22 Ma, including both the adaptation of novel characters and the
reduction of others. Thus, while viviparity can be disadvantageous, in
association with new Bauplans and/or behaviors, it can contribute to the
evolution of taxa with viviparous representatives that are slightly selectively
preferred.
PMID- 27614457
TI - Lactational exposure effect of polychlorinated biphenyl on rat Sertoli cell
markers and functional regulators in prepuberal and puberal F1 offspring.
AB - PURPOSE: Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative
environmental toxicants acting as endocrine disruptors. Many researches evidenced
that PCBs affect the male reproductive system in adult rats and it can transfer
from mother to offspring through milk. We investigated whether the lactational
exposure to PCBs affects the Sertoli cell function in F1 offspring. METHODS: Dams
were orally treated with different doses of PCB-Aroclor 1254 (1, 2 and 5 mg/kg
bw/day, respectively) from postpartum day 1-20. Male offspring rats were killed
on PND 21 and PND 60. Testes were used both for histological study and to isolate
Sertoli cell. Serum and testicular interstitial fluid (TIF) levels of
testosterone, ABP and estradiol were analyzed by ELISA method. The mRNA and
protein expressions of follicle-stimulating hormone (FSHR), androgen-binding
protein (ABP), Inhibinbeta, androgen receptor (AR) and estrogen receptor (ERbeta)
were studied using real-time PCR and immunoblotting, respectively. RESULTS: The
testicular architecture was altered in PCB-treated groups of both prepuberal and
puberal rats. Testosterone, estradiol and androgen-binding protein levels were
altered in both serum and TIF in PCB treated groups. The gene expression level of
FSHR, ABP, ERbeta and AR was decreased in a dose-dependent manner, whereas
Inhibinbeta gene expression level was increased in PCB-treated groups.
CONCLUSION: Lactational exposure to PCB affects both the histoarchitecture of
testis, Sertoli cell maker and functional regulators in both prepuberal and
puberal F1 male progeny.
PMID- 27614458
TI - Association between omentin-1, adiponectin and bone health under consideration of
osteoprotegerin as possible mediator.
AB - PURPOSE: Several studies implicated a crosstalk between bone and fat in the
pathogenesis of osteoporosis. Few studies indicated an association between
adiponectin and omentin-1 on the bone remodeling process and bone mineral
density, and suggested osteoprotegerin (OPG) as a mediator of this relationship.
However, only limited evidence on this relationship is available in humans.
Therefore, this study aimed to investigate the association between omentin-1,
adiponectin and broadband ultrasound attenuation (BUA) in peri-/premenopausal and
postmenopausal women, and to assess the role of OPG as a possible mediator.
METHODS: Data from the German population-based EPIC-Potsdam cohort comprising 637
women were analyzed. Multivariable-adjusted ANCOVA including age, BMI, waist
circumference, smoking status, education, physical activity, adiponectin or
omentin-1 and hormone use was used to investigate potential relationships between
the adipokines and BUA levels. A mediation analysis assessed the mediating effect
of OPG on the association of BUA and omentin-1 levels. RESULTS: Peri
/premenopausal women had higher BUA levels (112.5 +/- 10.1 dB/MHz), compared to
postmenopausal women (106.3 +/- 10.0 dB/MHz). In peri-/premenopausal women
neither adiponectin nor omentin-1 was significantly associated with BUA. In
postmenopausal women, adiponectin was not associated with BUA, but 10 % increase
in the omentin-1 concentration was significantly associated with 0.44 dB/MHz
lower BUA levels (p = 0.01). Omentin-1 was positively associated with OPG (p =
0.02); however, OPG was not significantly related to BUA (p = 0.62). CONCLUSION:
Our study provides evidence for an inverse association between circulating
omentin-1 and BUA levels in postmenopausal women. However, the present findings
do not support a mediating effect of OPG in the adipose tissue-bone pathway.
PMID- 27614459
TI - Investigation of timing preparation during response initiation and execution
using a startling acoustic stimulus.
AB - The purpose of the current study was to examine the processes involved in the
preparation of timing during response initiation and execution through the use of
a startling acoustic stimulus (SAS). In Experiment 1, participants performed a
delayed response task in which a two key-press movement was to be initiated 200
ms after an imperative signal (IS) with either a short (200 ms) or long (500 ms)
interval between key-presses. On selected trials, a SAS was presented to probe
the preparation processes associated with the initiation delay and execution of
the inter-key interval. The SAS resulted in a significant decrease in the
initiation time, which was attributed to a speeding of pacemaker pulses used to
time the delay interval, caused by an increased activation due to the SAS.
Conversely, the SAS delayed the short inter-key interval, which was attributed to
temporary interference with cortical processing. In Experiment 2, participants
performed a 500-ms delayed response task involving two key-presses 200 ms apart.
In this condition, the SAS resulted in significantly decreased initiation time
and a delayed inter-key interval (p = .053). Collectively, these results support
a different timeline for the preparation of the delay interval, which is thought
to be prepared in advance of the IS, and the inter-key interval, which is thought
to be prepared following the IS. This conclusion provides novel information with
regard to timing preparation that is consistent with models in which response
preparation, initiation, and execution are considered separate and dissociable
processes.
PMID- 27614460
TI - Methicillin resistance and biofilm production of Staphylococcus epidermidis
isolates from infectious and normal flora conjunctiva.
AB - PURPOSE: Coagulase-negative staphylococci have been reported to be the most
frequent cause of bacterial postoperative endophthalmitis. Biofilm formation is
the major virulence factor of Staphylococcus epidermidis and is often associated
with methicillin resistance. This study aims at evaluating the presence of
biofilm-producing and methicillin resistance genes (mecA) in S. epidermidis.
METHODS: S. epidermidis isolated from clinically infected sites (group 1) and
from normal human conjunctiva (group 2) were studied. All the isolates were
tested for their ability to produce biofilm by the conventional Christensen's
method and the presence of mecA by PCR using the 22-mer oligonucleotides as
primers. RESULTS: In total 20 isolates from group 1 and 22 from group 2 were
studied. Biofilm and mecA were detected in 15 (75 %) and in 14 (70 %) in group 1
as compared to 8 (36.3 %) and 4 (18.2 %) in group 2 (p = 0.016). Simultaneously,
biofilm production and presence of mecA genes were observed in 13/20 (65.0 %) in
group 1, and 4/22 (18.2 %) in group 2 (p = 0.002). Multi-resistance was observed
in 55 % in group 1 and 9 % in group 2 (p = 0.002); 57 % of the biofilm-producing
strains was multi-resistant in contrast to none of the non-producing strains. In
all multi-resistant strains, biofilm production was seen. CONCLUSIONS: Biofilm
formation capacity was widely distributed, particularly among mecA (+) S.
epidermidis strains, which also displayed a high diversity of antibiotic
resistance profiles.
PMID- 27614461
TI - The results of 25-gauge vitreoretinal surgery for optic disc pit-associated
maculopathy: a report of three cases and mini-review of the literature.
AB - PURPOSE: We report the outcomes of three consecutive patients with optic disc pit
associated maculopathy who were treated with 25-gauge pars plana vitrectomy,
internal limiting membrane (ILM) peeling, fluid-air exchange, barrage endolaser,
and sulfur hexafluoride (SF6) gas tamponade. CASE REPORT: Patients with optic
disc pit-associated maculopathy were treated with 25-gauge pars plana vitrectomy
followed by ILM peeling, fluid-air exchange, barrage endolaser, and gas tamponade
with 20 % SF6. All patients were asked to maintain a facedown position for 3 days
postoperatively. This technique resulted in complete retinal reattachment after
25-gauge vitrectomy, ILM peeling, fluid-air exchange, barrage endolaser, and 20 %
SF6 gas injection. The best-corrected visual acuity (BCVA) improved in all three
patients and successful anatomical results were achieved. There wasn't any
macular detachment in all cases at 20th week follow-up. CONCLUSIONS: Our outcomes
suggest that 25-gauge vitrectomy with ILM peeling, fluid-air exchange, barrage
endolaser, and SF6 gas tamponade appears to be an effective treatment option for
optic disc pit-associated maculopathy.
PMID- 27614462
TI - Angioid streaks in aagenaes syndrome.
AB - Aagenaes syndrome, also called lymphoedema cholestasis syndrome 1 (LSC1), is
characterized by neonatal intrahepatic cholestasis, often lessening and becoming
intermittent with age and severe chronic lymphoedema, mainly affecting the lower
extremities. The condition is autosomal recessively inherited, and the gene is
located on chromosome 15q. The locus, LCS1, was mapped to a 6.6 cM region on
chromosome 15. Angioid streaks are visible irregular crack-like dehiscences in
bruch's membrane that are associated with atrophic degeneration of the overlying
retinal pigment epithelium. Angioid streaks have been described to be associated
with pseudoxanthoma elasticum, paget's disease, sickle-cell anaemia, acromegaly,
Ehlers-Danlos syndrome, and diabetes mellitus, but also appear in patients
without any systemic diseases. Patients with angioid streaks are generally
asymptomatic, unless the lesions extend towards the foveola or develop
complications such as traumatic bruch's membrane rupture or macular choroidal
neovascularization.
PMID- 27614463
TI - Free ILM patch transplantation for recalcitrant macular holes; should we save
some internal limiting membrane for later?
PMID- 27614464
TI - Descemet stripping automated endothelial keratoplasty using corneas from elderly
donors.
PMID- 27614466
TI - Current Status of Renal Denervation in Hypertension.
AB - Over the past 7 years, prospective cohorts and small randomized controlled
studies showed that renal denervation therapy (RDN) in patients with resistant
hypertension is safe but associated with variable effects on BP which are not
substantially better than medical therapy alone. The failure of the most
rigorously designed randomized sham-control study, SYMPLICITY HTN-3, to meet the
efficacy endpoints has raised several methodological concerns. However, recently
reported studies and ongoing trials with improved procedural characteristics,
identification of patients with true treatment-resistant hypertension on
appropriate antihypertensive regimens further explore potential benefits of RDN.
The scope of this review is to summarize evidence from currently completed
studies on RDN and discuss future perspectives of RDN therapy in patients with
resistant hypertension.
PMID- 27614465
TI - Workplace Interventions to Prevent Disability from Both the Scientific and
Practice Perspectives: A Comparison of Scientific Literature, Grey Literature and
Stakeholder Observations.
AB - Purpose The significant individual and societal burden of work disability could
be reduced if supportive workplace strategies could be added to evidence-based
clinical treatment and rehabilitation to improve return-to-work (RTW) and other
disability outcomes. The goal of this article is to summarize existing research
on workplace interventions to prevent disability, relate these to employer
disability management practices, and recommend future research priorities.
Methods The authors participated in a year-long collaboration that ultimately led
to an invited 3-day conference, Improving Research of Employer Practices to
Prevent Disability, held October 14-16, 2015, in Hopkinton, Massachusetts, USA.
The collaboration included a topical review of the literature, group conference
calls to identify key areas and challenges, drafting of initial documents, review
of industry publications, and a conference presentation that included feedback
from peer researchers and a question/answer session with an expert panel with
direct employer experience. Results Evidence from randomized trials and other
research designs has shown general support for job modification, RTW
coordination, and organizational support, but evidence is still lacking for
interventions at a more granular level. Grey literature reports focused mainly on
job re-design and work organization. Panel feedback focused on organizational
readiness and the beliefs and values of senior managers as critical factors in
facilitating changes to disability management practices. While the scientific
literature is focused on facilitating improved coping and reducing discomforts
for individual workers, the employer-directed grey literature is focused on
making group-level changes to policies and procedures. Conclusions Future
research might better target employer practices by tying interventions to
positive workplace influences and determinants, by developing more participatory
interventions and research designs, and by designing interventions that address
factors of organizational change.
PMID- 27614467
TI - (1)H, (13)C, (15)N backbone and side-chain resonance assignment of Nostoc sp.
C139A variant of the heme-nitric oxide/oxygen binding (H-NOX) domain.
AB - The H-NOX (Heme-nitric oxide/oxygen binding) domain is conserved across
eukaryotes and bacteria. In human soluble guanylyl cyclase (sGC) the H-NOX domain
functions as a sensor for the gaseous signaling agent nitric oxide (NO). sGC
contains the heme-binding H-NOX domain at its N-terminus, which regulates the
catalytic site contained within the C-terminal end of the enzyme catalyzing the
conversion of GTP (guanosine 5'-triphosphate) to GMP (guanylyl monophosphate).
Here, we present the backbone and side-chain assignments of the (1)H, (13)C and
(15)N resonances of the 183-residue H-NOX domain from Nostoc sp. through solution
NMR.
PMID- 27614469
TI - Vascular lesions simulating bruising.
AB - Careful examination of the skin and soft tissues is a routine part of the
forensic autopsy to identify and characterise traumatic lesions. Three cases are
reported where benign vascular lesions presented as bruises. In case 1, a 44-year
old man with a history of epilepsy was found dead on the floor. Dissection of the
neck revealed a haemorrhagic area 15 mm * 1.5 mm, deep to the left thyrohyoid
muscle. In case 2, an 87-year-old man was found dead with a plastic bag over his
head attached to an opened cylinder of nitrogen gas. On the mucosal surface of
his upper lip, there was an apparent 5 mm blue/purple bruise. In case 3,
examination of the back of a 16-month-old girl revealed an apparent 15 mm bruise.
Histological examination of all three lesions revealed benign vascular lesions.
In the absence of microscopy, these lesions would have been considered traumatic
in origin, raising the possibility of inflicted trauma.
PMID- 27614470
TI - What Clinical Laboratorians Should Do in Response to Extremely Low Hemoglobin A1c
Results.
AB - Extremely low hemoglobin A1c (HbA1c) results below reference range are rare, and
the causes and clinical implications associated with low HbA1c results are not
well understood among clinical laboratorians. A case of extremely low HbA1c
results was reported, in which liver cirrhosis, subacute hemorrhage and recent
transfusion all contributed to the low result. This case illustrates when HbA1c
should not be used as a clinically relevant diabetes marker. However, low or
extremely low HbA1c (<5.0% or <4.0%) may occur in apparently healthy individuals.
When this occurs, it is an independent risk factor associated with liver
diseases, hospitalization, and all-cause mortality. From the clinical laboratory
perspective, the clinical cause of extremely low HbA1c should be determined, and
suggestions of different test utilization or increased health surveillance should
be given to care providers.
PMID- 27614468
TI - ER-localized adenine nucleotide transporter ER-ANT1: an integrator of energy and
stress signaling in rice.
AB - Most environmental perturbations have a direct or indirect deleterious impact on
photosynthesis, and, in consequence, the overall energy status of the cell.
Despite our increased understanding of convergent energy and stress signals, the
connections between photosynthesis, energy and stress signals through putative
common nodes are still unclear. Here we identified an endoplasmic reticulum (ER)
localized adenine nucleotide transporter1 (ER-ANT1), whose deficiency causes
seedling lethality in air but viable under high CO2, exhibiting the typical
photorespiratory phenotype. Metabolic analysis suggested that depletion of ER
ANT1 resulted in circadian rhythm disorders in sucrose synthesis and induced
sucrose signaling pathways, indicating that the ER is involved in the regulation
of vital energy metabolism in plants. In addition, the defect of ER-ANT1 triggers
ER stress and activates the unfolded protein response in plant cells, suggesting
ER stress and photorespiration are closely linked. These findings provide an
important evidence for a key role of ER-localized ER-ANT1 in convergent energy
and stress signals in rice. Our findings support the idea that ATP is a central
signal involved in the plant response to a variety of stresses.
PMID- 27614471
TI - Clonal Lymphoproliferations in a Patient With Common Variable Immunodeficiency.
AB - Common variable immunodeficiency (CVID) comprises a heterogeneous group of
disorders of humoral immunity, characterized by marked deficiencies in serum
immunoglobulins. Immune dysregulation causes susceptibility to recurrent
bacterial infections, as well as autoimmune and lymphoproliferative disorders.
Although the lymphoid cells comprising the atypical proliferations are often
clonally related, their malignant potential and clinical significance differ from
similar lesions in individuals with immunocompetence. Herein, we describe a
Caucasian woman with CVID who over 7 years developed multiple clonal
lymphoproliferative lesions, comprising a spectrum of morphologic
characteristics. Many of the lesions harbored distinct clonal populations. Though
a majority responded to conservative intervention, 1 lesion persisted, met the
diagnostic criteria for diffuse large B-cell lymphoma, and responded well to
conventional chemotherapeutic treatment. The patient subsequently developed
additional lymphoproliferations, but the lesions were clonally distinct and
responded to conservative therapy. The clinical course of this patient emphasizes
the variable nature of lymphoproliferative lesions arising in patients with CVID
and underscores an individualized approach to pathologic interpretation and
diagnostic intervention.
PMID- 27614472
TI - The role of particular tick developmental stages in the circulation of tick-borne
pathogens affecting humans in Central Europe. 3. Rickettsiae.
AB - Ixodes ricinus, Dermacentor reticulatus and D. marginatus ticks are the most
important vector for Rickettsia spp. in Central Europe. Ticks sustain rickettsial
transmission cycles transovarially and transstadially, it makes enable the
rickettsial circulation in the tick population in the absence of vertebrate
competent reservoir. Rickettsia helvetica is transmitted by I. ricinus tick; the
highest rates of infection are noted in adult females, lower in males and in
nymphs. All tick developmental stages apart males are able to infect mammal hosts
and humans. The potential animal reservoir could be wild boar, the role of deer
is unclear; small rodents maintain the tick population. Rickettsia slovaca is
transmitted by D. marginatus and D. reticulatus ticks. The available data suggest
the role of wild boars and Apodemus mice as animal reservoir. The ticks able to
infect human are adults D. marginatus. Rickettsia raoultii is transmitted by D.
marginatus and D. reticulatus. The infections of mammals are not recorded. As in
Rickettsia slovaca, human can be infected by adults D. marginatus. Rickettsia
monacensis is transmitted in Central Europe by I. ricinus tick (apart males),
although there is a documented infection of Dermacentor ticks. The differences in
the infection rates of tick's larvae, nymphs and adults suggest the limited role
of transovarial transmission, and the participation of mammals in the zoonotic
cycle, being the source of infection for larvae and nymphs. KEY WORDS: SFG,
Rickettsia slovaca, Rickettsia helvetica, Rickettsia raoultii, Rickettsia
monacensis, ticks.
PMID- 27614473
TI - Specificity of mass spectrometry (MALDI-TOF) in the diagnosis of Babesia canis
regarding to other canine vector-borne diseases.
AB - The canine vector-borne diseases (CVBD) is a term, which describes a range of
infectious or/and parasitic diseases whose etiological agents are transmitted by
vectors. CVBD are becoming more widely in the world in relation to global warming
and the increasing number of infected vectors. The aim of this study was to
assess rapid mass spectrometry (MS) - based proteomics analyses for diagnosis of
Babesia canis, Anaplasma phagocytophilum and Borrelia burgdorferi infections in
dogs. The study was conducted on four groups of dogs - healthy dogs (group 1,
n=10) and dogs infected with B. canis (group 2, n=20), A. phagocytophilum (group
3, n=20) and B. burgdorferi (group 4, n=20) which demonstrated symptoms of the
diseases. The MALDI-TOF (Matrix Assisted Laser Desorption Ionization with Time of
Flight detector) MS technique revealed the presence of specific protein fraction
of 51-52 kDa only in the blood serum of all the animals infected with the B.
canis protozoa. The proteins are suspected to be disease markers, whereas the
MALDI-TOF technique itself has high specificity and sensitivity and can be
applied in the diagnosis of canine babesiosis. KEY WORDS: Anaplasma
phagocytophilum, Babesia canis, Borrelia burgdorferi, MALDI-TOF, proteomics.
PMID- 27614474
TI - A massive invasion of Parafasciolopsis fasciolaemorpha in elk (Alces alces) in
Lublin Province, Poland.
AB - Liver fluke Parafasciolopsis fasciolaemorpha is a parasite typical of elk (Alces
alces). The present study describes the identification of a massive invasion of
the liver fluke P. fasciolaemorpha in an elk in the Sobibor Landscape Park,
Eastern Poland. In February 2016, samples of liver and faeces were collected from
the elk during postmorte examination. A section of liver tissue and three grams
of faeces were examined for the presence of flukes or fluke eggs by decantation.
In total, 11,150 juvenile and mature flukes of P. fasciolaemorpha were found in
the examined liver. Multiple cavities with distinct walls, filled with dark
liquid, trematodes, fluke eggs and cellular detritus were seen in the cross
section of the parenchyma. Additionally, some of the bile ducts were plugged with
calcerous deposits. The three grams of examined faeces were found to contain 322
grey and golden-coloured eggs of P. fasciolaemorpha. The presence of such a
massive infection of P. fasciolaemorpha in the examined elk has a significant
impact on the health of the individual. We can assume P. fasciolaemorpha has a
significant influence on the health and abundance of the entire elk population in
Poland. KEY WORDS: Parafasciolopsis fasciolaemorpha, elk, Sobibor Landscape Park,
Poland.
PMID- 27614475
TI - Prevalence of anti-Neospora caninum antibodies in Iranian goats.
AB - Many species of animals play the role of intermediate host for Neospora caninum.
Although the neosporosis has a global distribution, however there is no
information on goats' infection in Iran. The main goal of present study was to
determine the seroprevalence of N. caninum in goats of western Iran. A total of
450 sera were taken and analyzed for antibodies to N. caninum using ELISA
technique. Of those, 28 (6.2%) examined goats were found to be seropositive (95%,
CI=6.2+/-2.2%). In which male goats (11.1%) had the highest IgG against N.
caninum with more than 2 years-old (54.4%). There was significant difference
between prevalence and age. Positive association were in animals with history of
abortion (18/30, 60%) and IgG against N. caninum. No correlations were found
between male and female. This was the first report on N. caninum infection in
Iranian goats and may be responsible for abortion and economic losses in goat
husbandry in the region. KEY WORDS: goat, Neospora caninum, ELISA, Iran.
PMID- 27614476
TI - Cephenemyia stimulator (Diptera) infection in roe deer (Capreolus capreolus) from
Krakow area, southern Poland.
AB - The aim of the study was to determine the prevalence of botfly (Diptera:
Oestridae) larvae infection in roe deer populations (Capreolus capreolus) in the
Krakow area on the basis of necropsy and questionnaire surveys. Hunters were
surveyed about the age and sex of hunted animals, and the origin of their
habitat. All parasite specimens were identified to species in the laboratory. The
parasites were found in the nasal cavities, esophagus, and larynx of male roe
deer aged 3-8 years, living in forest habitats. The level of infection was
relatively low (13%), with the intensity ranging from 1 to 10 larvae per host.
Although no fly larvae were found during the dissection of roe deer carcasses,
the parasites received from the hunters were identified as Cephenemyia stimulator
botflies. These findings are supported by the evidence drawn from the
questionnaires completed by the hunters. KEY WORDS: parasites, Cephenemyia
stimulator, Capreolus capreolus, necropsy, questionnaire study, Poland.
PMID- 27614477
TI - Benzimidazole resistance in the ovine Haemonchus contortus from southern Poland -
coproscopical and molecular findings.
AB - Anthelmintic resistance within nematodes has become a very common issue, however,
the data about its occurrence in the gastrointestinal nematodes of sheep in
Poland are very limited. This study was carried out in order to evaluate the
presence of benzimidazole resistance in highly pathogenic Haemonchus contortus by
means of parasitological and molecular techniques. The research represents the
first Polish attempt to confirm the presence of a mutation at codon 200 of the
beta-tubulin isotype 1 gene in H. contortus by PCR-RFLP. The occurrence of this
mutation indicates the risk of ineffective benzimidazole treatment, nowadays
commonly used for parasite control in Poland. The resistant parasites were
detected by means of FECRT in a sheep flock (30 individuals) from southern
Poland. To confirm the resistance on the molecular level, primers designed
according to the sequences available in Genebank were used to detect the
mutation. Unfortunately, as the PCR product was shorter than required (403 bp),
further analyses are needed. The obtained results may indicate the high
variability within the parasite population. Hence, it is essential to adapt the
reaction conditions to our geographic strain of the nematode - and further
analyses are required. KEY WORDS: Haemonchus contortus, benzimidazole resistance,
PCR, Poland.
PMID- 27614478
TI - Dermacentor reticulatus (Fabricius, 1794) and Babesia canis (Piana et Galli
Valerio, 1895) as the parasites of companion animals (dogs and cats) in the
Wroclaw area, south-western Poland.
AB - Tests performed in 2013 and 2014 revealed the occurrence of three tick species
parasitizing pet cats and dogs in the Wroclaw Agglomeration. In total, 1,455 tick
specimens were removed from 931 hosts (760 dogs and 171 cats) in 18 veterinary
clinics. The dominant tick species was Ixodes ricinus (n=1272; 87.4%), followed
by I. hexagonus (n=137; 9.4%) and Dermacentor reticulatus (n=46; 3.2%). Females
were the most often collected development stage among I. ricinus and D.
reticulatus, and nymphs among I. hexagonus. Additionally, D. reticulatus ticks
(n=337) were then collected from vegetation in the Wroclaw area to detect Babesia
canis; however, none was found positive. Only 9.0% of dog blood samples sent to
VETLAB were positive for Babesia spp. Negative results for B. canis from ticks
may result from the short period of the occurrence of D. reticulatus in the
Wroclaw area and therefore the vectorpathogen cycle may not have been fully
established at the time of the study. Nevertheless, D. reticulatus is expanding
its range, and the size of its population in the Wroclaw Agglomeration is
increasing. The presence of the pathogenic Babesia spp. combined with the
occurrence of its main vector D. reticulatus, suggests that the epizootiological
situation in the area can change and may pose a new veterinary problem in the
future. KEY WORDS: Dermacentor reticulatus, Babesia canis, pets, Wroclaw, Poland.
PMID- 27614479
TI - Status of tick infections among semi-wild cattle in Arunachal Pradesh, India.
AB - To explore the seasonal prevalence of tick infections in mithun (Bos frontalis)
and yak (B. grunniens) a study was conducted in Papum Pare district, Kurung-Kumey
district and West Kameng district of Arunachal Pradesh, India from December 2012
to November 2014. Adult ticks were collected from both the animals during the
month of December 2012 to November 2014. Ectoparasites were identified on the
basis of their morpho-anatomical features observed through light microscope. A
total of nine different species of ectoparasites recovered belong to the family
Ixodidae are Rhipicephalus (B.) microplus, R. (B.) geigy, Haemaphysalis davisi,
H. darjeeling, H. longicornis, H. bispinosa, Ixodes acutitarsus, I. ricinus and
Rhipicephalus sanguineus. Out of 129 mithun examined during the survey R. (B.)
microplus and H. davisi showed 100% prevalence of infections throughout the year
followed by H. longicornis (35.65%), H. bispinosa (30.23%), R. (B.) geigy
(25.58%), I. acutitarsus (20.93%), H. darjeeling (7.75%), I. ricinus (1.55%) and
Rhipicephalus sanguineus (0.77%). Similarly, all 21 yak examined revealed to be
infected with R. (B.) microplus (100%) followed by I. acutitarsus (51.14%) and H.
davisi (33.33%). In mithun the rate of infection due to all the nine
ectoparasites rose to a peak during June to August. Except for the winter season,
R. (B.) geigy occurred throughout the year. I. acutitarsus and H. darjeeling
showed their occurrence throughout the year except during spring, however, I.
ricinus and R. sanguineus occurs only during rainy season. KEY WORDS: Bos
frontalis, B. grunniens, ecto-parasite, Arunachal Pradesh, India.
PMID- 27614480
TI - Presence of intracellular viruses in human Cryptosporidium isolates.
AB - Cryptosporidium is a major cause of diarrheal illness mainly in children and
immunocompromised adults. Disease severity ranges from asymptomatic or self
limited gastroenteritis to acute or chronic diarrhoea which may be associated
with systemic features. Intracellular viruses that reside in many parasites have
been incriminated in pathogenesis of diseases like trichomoniasis, leishmaniasis
etc. Thus we attempted to detect and quantitate the intracellular viruses in
Cryptosporidium isolates and sought to seek a relationship if any, with clinical
features. Cryptosporidia in stool samples from immunocompromised patients and
children were identified by microscopy and species differentiated by PCR-RFLP of
18s rRNA; further subgenotyped by sequencing of GP60 region. Copy number of dsRNA
virus and 18srRNA was calculated in 56 Cryptosporidium isolates (39 C. hominis
and 17 C. parvum). Viral copy number per oocyst was calculated as ratio of dsRNA
virus copy number to 18s rRNA copy number. Viruses were detected in all the
isolates. Mean CSpV/RNA ratio was 0.17+/-0.4 for C. hominis isolates compared
with 0.12+/-0.11 for C. parvum isolates, however this difference was not
statistically significant. Similarly no association of diarrhoea, vomiting, cough
and fever was found with either CSpV copy number or with CSpV/rRNA ratio. KEY
WORDS: Cryptosporidium, virus, immunocompromised, diarrhoea.
PMID- 27614481
TI - Disseminated cysticercosis: role of whole body Magnetic Resonance Imaging.
AB - Cysticercercosis is a parasitic infection that is commonly seen in developing
countries. Treatment of cysticercosis can precipitate an intense inflammatory
response which may further worsen the symptoms. Whole body MRI is an upcoming
tool for screening of diseases. It can be acquired in the same setting as a brain
MRI in reasonable time without any additional hardware. We present a case wherein
whole body MRI was used to evaluate disseminated cysticercosis. It can prove as
useful screening tool to gauge the disease load and modify the treatment plan
accordingly, especially in endemic areas. KEY WORDS: disseminated cysticercosis,
whole body MRI.
PMID- 27614483
TI - Observations on the clinical features of sickle cell disease in early childhood.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614484
TI - Osteoporosis in postmenopausal Saudi women using dual X-ray bone densitometry.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614482
TI - Reporting in the clinical trials evaluating scabies treatments.
PMID- 27614485
TI - Serum cholesterol concentrations in prisoners charged with violent crimes.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614486
TI - Cytosine arabinoside, mitoxantrone, and etoposide in the treatment of adult
patients with previously untreated acute myeloid leukemia.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614487
TI - Internal audit of blood bank.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614488
TI - Incidence of Herpes (Pemphigoid) Gestationis inRiyadh Armed Forces Hospital
Programme.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614489
TI - Terminal Latency Index: A distinctive diagnostic criterion for carpal tunnel
syndrome.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614490
TI - Pneumatic dilation of cardiac achalasia using low compliance balloon: University
Hospital experience.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614491
TI - Brucellosis in humans associated with animals.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614492
TI - Ochronotic arthritis of knee.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614493
TI - Nocardia asteroides in renal transplant recipients.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614494
TI - Anesthesia of a patient who underwent resection of small bowel leiomyosarcoma.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614495
TI - Infected rectus sheath hematoma: An unrecognized cause of intestinal obstruction.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614496
TI - Migraine and tension type headaches.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614497
TI - [Modalities of breast cancer irradiation in 2016: Aims and indications of
intensity modulated radiation therapy].
AB - Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving
and intensity-modulated radiation therapy is being increasingly considered for
the management of these tumours. Here, we propose a review of intensity-modulated
radiation therapy planning issues, clinical toxicities and indications for breast
cancer.
PMID- 27614498
TI - [Conformal radiotherapy for vertebral bone metastasis].
AB - Analgesic external beam radiation therapy is a standard of care for patients with
uncomplicated painful bone metastases and/or prevention of bone complications. In
case of fracture risk, radiation therapy is performed after surgery in a
consolidation of an analgesic purpose and stabilizing osteosynthesis.
Radiotherapy is mandatory after vertebroplasty or kyphoplasty. Spinal cord
compression - the only emergency in radiation therapy - is indicated
postoperatively either exclusively for non surgical indication. Analgesic re
irradiation is possible in the case of insufficient response or recurrent pain
after radiotherapy. Metabolic radiation, bisphosphonates or denosumab do not
dissuade external radiation therapy for pain relief. Systemic oncological
treatments can be suspended with a period of wash out given the risk of
radiosensitization or recall phenomenon. Better yet, the intensity modulated
radiotherapy and stereotactic radiotherapy can be part of a curative strategy for
oligometastatic patients and suggest new treatment prospects.
PMID- 27614499
TI - [Clinical to target volume margins determination in radiotherapy for anal
cancers].
AB - There are very few data on the expansion from the clinical target volume (CTV) to
the planning target volume (PTV) in the anal cancer treatment. This article aims
to collect the different elements needed for the construction of a PTV from
scientific data based on a literature analysis. We reviewed the articles
published in the medical literature from the last 20years. They concerned setup
errors and internal organ mobility of the different volumes of patients treated
by conformational radiotherapy and intensity-modulated radiotherapy (anal canal,
meso-rectum, common, intern and extern, inguinal and pre-sacral lymph nodes). CTV
to PTV margins admitted in the guidelines and atlas of consensus groups (SFRO,
RTOG, AGITG) are from 0.7 to 1cm in all directions, based on expert's opinions
but not on scientific data. There are no specific studies on the canal anal
mobility. Most of the data are from other pelvis cancers (gynecologic, rectum and
prostate). Setup errors can be reduced by daily imaging. Patient repositioning
and immobilization modalities are mostly local habits rather than scientific
consensus. A three-dimensional 1cm margin is generally admitted. Margins
reduction must be careful and has to be assessed.
PMID- 27614500
TI - [Brachytherapy for sarcomas].
AB - The standard of care for local treatment for extremities soft tissue sarcomas
relies on conservative surgery combined with external beam radiotherapy.
Brachytherapy can be realized instead of external beam radiotherapy in selected
cases, or more often used as a boost dose on a limited volume on the area at
major risk of relapse, especially if a microscopic positive resection is
expected. Close interaction and communication between radiation oncologists and
surgeons are mandatory at the time of implantation to limit the risk of side
effects. Long-term results are available for low-dose rate brachytherapy.
Nowadays, pulsed dose rate or high-dose-rate brachytherapy are more often used.
Brachytherapy for paediatric sarcomas is rare, and has to be managed in reference
centres.
PMID- 27614501
TI - [Radiotherapy for soft tissue sarcomas: Technical evolution and impact on
clinical benefit].
AB - The standard treatment for extremity soft tissue sarcomas is based on the
association of surgery and radiotherapy. This strategy allows local control
improvement with the risk of increased toxicity. There is therefore a growing
interest to identify those patients who will benefit from radiotherapy and those
who will have the same local control with surgery alone. Furthermore, the
development of toxicity has been correlated with the extension of the irradiated
volume and the volume receiving high doses. Technological development as
intensity modulated radiotherapy and image-guided radiotherapy allows limited
irradiated volume improving the protection of the organs at risk leading to
clinical benefit improvement. Moreover, efforts are being done to improve local
control for the patients at high risk of local relapse. In this paper, we discuss
all these mentioned aspects.
PMID- 27614502
TI - [Audits of the quality management system and safety in radiotherapy: Lessons
learned and future prospects].
AB - The external audit of the management system of quality and safety in radiotherapy
by quality managers of the French Association of Quality and Safety in
Radiotherapy (AFQSR) is an opportunity to exchange good practices, returns of
experience, effectiveness and weaknesses of the quality system, and its
perceptions by all the teams. We present the results of the first audits
conducted, and the results of a survey on the perception of quality at national
level.
PMID- 27614503
TI - [Interest of positioning control in onboard imaging and its delegation to the
therapists].
AB - The delegation of the on board imaging position control, from the radiation
oncologist to the therapist, is justified by the generalization of the image
guided radiotherapy techniques which are particularly time consuming. This
delegation is however partial. Indeed, the validation of the position by the
therapist can be clearly performed when the registration is based on bony
landmark or fiducial. The radiation oncologist needs however to make the
validation in case of large target displacement, in more complex soft tissue
based registration, and in case of stereotactic body radiation therapy. Moreover,
this delegation implies at least three conditions which are first the training of
the staff, then the formalization of the procedures, responsibilities and
delegations and finally, the evaluation of the practices of IGRT.
PMID- 27614504
TI - [What is the role of intraoperative radiotherapy in breast cancer treatment?].
AB - Breast-conserving surgery followed by whole breast postoperative irradiation is
considered to be the current standard treatment for patients with early stage
breast cancer. It allows an excellent local tumour control with 6% of local
recurrence. Over the last years, partial breast radiotherapy has been developed
to reduce treatment volume and duration. Intraoperative radiotherapy is one of
the techniques. It offers an excellent delineation of the tumour bed and high
normal tissue sparing. This purpose of this review is to describe the different
intraoperative radiotherapy techniques available, to assess their potential
clinical efficiency and tolerance, the recommendations for new practice with a
selected population of patients and for future research.
PMID- 27614505
TI - [Position-checking by imaging embarked there tomotherapy and the delegation to
the radiology technician].
AB - Tomotherapy is a technique of IMRT and IGRT using a linear accelerator and a
helical CT-scanner. To reach this targeting of precision, the repositioning of
the patient is essential. The use of a contention adapted according to the
location of the disease and the morphology of the patient is necessary for the
safety of this one and the treatment. Once the patient positioned on the
reference table, technicians of imager's team check by the acquisition of helical
imagery with the reference CT-scanner the position of the patient, the zone of
the PTV and healthy organs in the protected surroundings. At first, adjustment
will be made automatically on three planes of the space (axial, sagittal,
frontal) and three rotations (pitch, roll and yaw) by the device of treatment,
then the technicians of imagery will bring a modification of these recalls
manually. After validation, the processing will then be made in complete safety
for the patient and the nursing. This check by MVCT is daily before every session
of processing. It is made by the technicians of imagery. The radiation oncologist
confirms the images at j0, then controls once a week MVCT. Traceability in the
file of the patient of the various marks (osseous and?or soft tissue) necessary
for the daily gaps will be noted by this one to delegate to the technicians of
imagery the validation of the MVCT before every session.
PMID- 27614506
TI - [Margin determination from clinical to planning target volume for lung cancer
treated with conformal or intensity-modulated irradiation].
AB - Technological progress in radiotherapy enables more precision for treatment
planning and delivery. The margin determination between the clinical target
volume and the planning target volumes stem from the estimation of geometric
uncertainties of the tumour localization into the radiation beam. The inner
motion complexity of lung tumours has led to the use of 4D computed tomography
and nurtures specific dosimetric concerns. Few strategies consisting in
integrating tumour motion allow margin reduction regarding inner movements. The
patient immobilization and onboard imagery improvement decrease the setup
uncertainties. Each step between the initial planning imagery and treatment
delivery has to be analysed as systematic or random errors to calculate the
optimal planning margin.
PMID- 27614507
TI - [Intensity-modulated radiotherapy of head and neck cancers: Dose effects on the
ocular, orbital and eyelid structures].
AB - Radiation-induced damage of ocular, orbital and eyelid structures are mainly
reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume
relationships are, however, inaccurate due to the small volume of most of the
organs at risk involved and limited ability of irradiation techniques to spare
these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The
ability of newest radiation techniques including IMRT and proton therapy to
generate steep dose gradients may yield more accurate models in the future. Some
toxicities are severe and irreversible, leading to vision loss, as in the case of
radiation-induced optic neuropathy for which curative treatments are suboptimal.
Other toxicities can lead to reversible vision loss but can be surgically
corrected, as is the case for radiation-induced cataract. In this paper, we will
review the dose effects for the ocular; orbital and eyelid structures.
PMID- 27614508
TI - [Indications and results for protontherapy in cancer treatments].
AB - Purpose was to summarize results for proton therapy in cancer treatment. A
systematic review has been done by selecting studies on the website
www.pubmed.com (Medline) and using the following keywords: proton therapy,
radiation therapy, cancer, chordoma, chondrosarcoma, uveal melanoma,
retinoblastoma, meningioma, glioma, neurinoma, pituitary adenoma,
medulloblastoma, ependymoma, craniopharyngioma and nasal cavity. There are
several retrospective studies reporting results for proton therapy in cancer
treatments in the following indications: ocular tumors, nasal tumors, skull-based
tumors, pediatric tumors. There is no prospective study except one phase II trial
in medulloblastoma. The use of proton therapy for these indications is due to
dosimetric advantages offering better tumor coverage and organ at risk sparing in
comparison with photon therapy. Clinical results are historically at least as
efficient as photon therapy with a better toxicity profile in pediatric tumors
(cognitive and endocrine functions, radiation-induced cancer) and a better
tumoral control in tumors of the nasal cavity. Clinical advantages of proton
therapy counterbalance its cost especially in pediatric tumors. Proton therapy
could be used in other types of cancer. Proton therapy showed good outcome in
ocular, nasal tumors, pediatric, skull-based and paraspinal tumors. Because of
some dosimetric advantages, proton therapy could be proposed for other
indications in cancer treatments.
PMID- 27614509
TI - [Radiotherapy for localized gastric and orbital MALT lymphomas].
AB - Primary gastric and orbital MALT lymphomas are both low grade (indolent) B-cell
non-Hodgkin's lymphomas. Traditionally, these tumors are radiosensitive and have
a good prognosis. In localized orbital and stages IE-IIE gastric MALT lymphomas
without Helicobacter pylori infection or in case of persistent H. pylori
infection after eradication therapy, several retrospective studies have shown
that radiotherapy was an effective and well-tolerated treatment.
PMID- 27614510
TI - [Technical aspects of protontherapy: Setup, equipment and radioprotection].
AB - The number of protontherapy facilities is still increasing rapidly with more than
30 ongoing projects and close to 60 currently under operation. Although the
technology is now validated and robust, a proton facility cannot be considered as
a standard radiation therapy equipment: its constraints in terms of building,
services, project management are of paramount impact at the level of the
hospital. Therefore, a protontherapy project must be carefully considered and
prepared, which is mandatory for further fluid and efficient clinical operation.
PMID- 27614512
TI - [Role of surgery in the management of vertebral metastases. General revue].
AB - The spine is the most common site of skeletal metastases. Treatment decisions for
patients with spinal metastases can be challenging and greatly depend on survival
prognosis. Surgery remains a valuable weapon in the therapeutic arsenal. A review
of the literature describing the role of surgery, the various surgical approaches
and the prognostic scores available for the management of spinal metastases was
performed and summarized. Surgery for spinal metastases has 3 main objectives:
management of pain, achievement of mechanical stability and preservation or
restoration of neurological function. A variety of surgical approaches are
available and depend on location of tumor, presence of instability, neurological
status, oncologic prognosis, general performance status and subsequent treatment
measures. The goal of any therapeutic course for a spinal metastasis is the best
oncologic and functional result with the least aggressive treatment. Novelty
surgical and adjunctive measures allow a multidisciplinary approach to the
metastatic spine.
PMID- 27614511
TI - [Stereotactic body radiation therapy for spinal metastases].
AB - After the liver and lungs, bones are the third most common sites of cancer
metastasis. Palliative radiotherapy for secondary bone tumours helps relieve
pain, improve the quality of life and reduce the risk of fractures. Stereotactic
body radiotherapy can deliver high radiation doses with very tight margins, which
has significant advantages when treating tumours close to the spinal cord. Strict
quality control is essential as dose gradient at the edge of the spinal cord is
important. Optimal schedule is not defined. A range of dose-fractionation
schedules have been used. Pain relief and local control are seen in over 80%.
Toxicity rates are low, although vertebral fracture may occur. Ongoing
prospective studies will help clarify its role in the management of
oligometastatic patients.
PMID- 27614513
TI - CTV to PTV in cervical cancer: From static margins to adaptive radiotherapy.
AB - Intensity-modulated radiotherapy (IMRT) is increasingly used in order to minimize
the gastrointestinal, genitourinary, and hematological toxicity in cervical and
uterine cancers. However, the benefit of this high-precision approach is
detracted by the margins applied to the clinical target volume (CTV) to generate
the planning tumor volume (PTV), taking into account tumor and surrounding organs
movements, deformations, and volume changes. Adequate PTV margins should be large
enough to prevent geographical misses, but not excessive, which might end the
benefit from IMRT. The objectives of this review were: (a) to present the
evidence available for the determination of CTV-PTV margin for uterine cancers;
(b) to highlight the impact of these margins in the context of adaptive
radiotherapy; and (c) to discuss the role of the PTV concept in intracavitary
brachytherapy.
PMID- 27614514
TI - [Role of functional imaging in the definition of target volumes for lung cancer
radiotherapy].
AB - Functional imaging with positron emission tomography (PET) is interesting to
optimize lung radiotherapy planning, and probably to deliver a heterogeneous dose
or adapt the radiation dose during treatment. Only fluorodeoxyglucose (FDG) PET
computed tomography (CT) is validated for staging lung cancer and planning
radiotherapy. The optimal segmentation methods remain to be defined as well as
the interest of "dose painting" from pre-treatment PET (metabolism: FDG) or
hypoxia (fluoromisonidazole: FMISO) and the interest of replanning based on
pertherapeutic PET.
PMID- 27614515
TI - [Clinical to planning target volume margins in prostate cancer radiotherapy].
AB - The knowledge of inter- and intrafraction motion and deformations of the
intrapelvic target volumes (prostate, seminal vesicles, prostatectomy bed and
lymph nodes) as well as the main organs at risk (bladder and rectum) allow to
define rational clinical to planning target volume margins, depending on the
different radiotherapy techniques and their uncertainties. In case of image
guided radiotherapy, prostate margins and seminal vesicles margins can be between
5 and 10mm. The margins around the prostatectomy bed vary from 10 to 15mm and
those around the lymph node clinical target volume between 7 and 10mm.
Stereotactic body radiotherapy allows lower margins, which are 3 to 5mm around
the prostate. Image-guided and stereotactic body radiotherapy with adequate
margins allow finally moderate or extreme hypofractionation.
PMID- 27614516
TI - [Hypofractionated whole breast irradiation (WBRT): Results and indications].
AB - Breast irradiation after breast-conserving surgery is essential for maximizing
local control and overall survival. The increase of breast cancer (BC) incidence,
constraints of classical five weeks (w) radiation regimens and scarcity of
radiotherapy units have led to test short hypofractionated WBRT schemes. One
pilot study and three prospective randomized trials have tested various
hypofractionated regimens of WBRT. About 7000 patients were included and follow
up ranged from 5 to 12 years. The conclusion of these trials is similar, showing
local control and toxicity equivalent to these of the standard regimens. Three
schemes are now clearly validated: 42.5Gy/16fr/3w, 40Gy/15fr/3w, or 42Gy/13fr/5w.
However, the majority of included patients had favorable prognostic factors, were
treated to the breast only and the boost dose, when indicated, was delivered with
a standard fractionation. Therefore, we recommend the regimens preferentially in
patients treated to the breast only, and without nodal involvement. These studies
did not evaluate the addition of a boost dose with a hypofractionated scheme. If
a boost is to be given, a standard fractionation should be used. Particular care
should be taken to avoid heterogeneities leading to high fraction doses to organs
at risk (lung and heart).
PMID- 27614517
TI - [Role of radiotherapy in the treatment of NK/T-cell nasal type and primary
cerebral lymphomas].
AB - The head and neck are common sites for extranodal non-Hodgkin lymphomas.
Radiotherapy plays an important role in the treatment of low-grade lymphomas,
with curative or palliative intent. In the case of high-grade lymphomas, its
combination with chemotherapy is debated. Its role is however undeniable in two
specific entities: NK/T-cell lymphoma NK/T nasal type, and primary central
nervous system lymphomas, which are the subject of this review.
PMID- 27614518
TI - [Computed tomography imaging of non-small cell lung cancer].
AB - Computed tomography (CT) plays a key role in the initial evaluation of non-small
cell lung cancer. It allows initial staging and helps targeting lesions for
pathological analysis. The aim of initial imaging work-up is to differentiate
between localized disease, eligible to a local treatment, and advanced disease
requiring medical treatment. CT is very useful for the assessment of local
extension but is less accurate than positron emission tomography (PET)-CT for the
assessment of lymphatic and metastatic spread. However, initial staging should
include CT examination of the brain and upper abdomen, and PET-CT should be only
be performed in patients eligible to a local treatment after initial CT
assessment. Propositions for the 8th edition of lung cancer TNM bring several
changes for T staging. In particular, the weight of lesion size is increased.
Similarly, N1 and N2 stages are now divided in subgroups according the number of
involved stations.
PMID- 27614519
TI - [Intensity modulated radiotherapy for head and neck cancer, dose constraint for
normal tissue: Cochlea vestibular apparatus and brainstem].
AB - Modern techniques such as intensity modulated radiation therapy (IMRT) have been
proven to significantly decrease the dose delivered to the cochleovestibular
apparatus, limiting consecutive toxicity especially for sensorineural hearing
loss. However, recent data still report a 42% rate of radio-induced hypoacusia
underscoring the need to protect the cochleovestibular apparatus. Due to the
small size of the cochlea, a precise dose-volume analysis could not be performed,
and recommendations only refer to the mean dose. Confusing factors such as age,
concomitant chemotherapy, primary site and tumor stage should be taken into
account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy
have been proven better at sparing the cochlea in comparison with 3D CRT.
Brainstem radio-induced injuries were poorly studied because of their infrequency
and the difficulty of distinguishing between necrosis and tumor progression in
the case of a primary tumor located at the base of skull. The following
toxicities have been described: brainstem focal radionecrosis, cognitive
disorders without dementia, cranial nerve injuries and sensori motor disability.
Maximal dose to the brainstem should be kept to < 54Gy for conventional
fractionation. This dose could be exceeded (no more than 10mL should receive more
than 59Gy), provided this hot spot is located in the peripheral area of the
organ.
PMID- 27614520
TI - [Establishing margins from CTV to PTV in breast cancer treatment].
AB - The benefit of postoperative radiotherapy for breast cancer both in terms of
local control and overall survival is widely acknowledged. Today, technological
advances in simulation imaging and positioning control enable the definition of
new margins from CTV to PTV. Improvements in mathematical modeling of random and
systematic errors impact the treatment plans. However, there is no universal
absolute value to consistently determine the margins from CTV to PTV. It is down
to each centre to assess and correct as much as possible uncertainties due to
positioning and internal movements depending on techniques and methods used for
the implementation of treatment and monitoring. IMRT and respiratory gating
techniques for breast radiotherapy will be considered more systematically in the
years to come.
PMID- 27614522
TI - [Radiotherapy for small cell lung carcinoma].
AB - Radiotherapy for small cell lung carcinoma has known significant improvements
over the past 10 years especially through routine use of PET-CT in the initial
work-up and contouring before treatment. Prophylactic cranial irradiation remains
a standard of care for locally advanced disease and is a subject of controversy
for metastatic disease. A new indication for thoracic radiotherapy may soon arise
for metastatic disease, still confirmation studies are ongoing.
PMID- 27614521
TI - [Radiotherapy and targeted therapy/immunotherapy].
AB - Thanks to recent advances achieved in oncologic systemic and local ablative
treatment, the treatments become more and more efficient in term of local control
and overall survival. Thus, the targeted therapies, immunotherapy or stereotactic
radiotherapy have modified the management of patients, especially in case of
oligometastatic disease. Many questions are raised by these innovations,
particularly the diagnosis and management of new side effects or that of the
combination of these different treatments, depending on the type of primary
tumor. Fundamental data are available, while clinical data are still limited.
Ongoing trials should help to clarify the clinical management protocols. This
manuscript is a review of the combination of radiotherapy and targeted
therapy/immunotherapy.
PMID- 27614523
TI - [Methodological aspect, application and evaluation of the delegation of tasks of
the recalage of images].
AB - Application and evaluation of the delegation of tasks of the recalage of images,
the example of the authorization of the manipulators of the unity (unit) of
radiotherapy of the Hospital center of Quimper.
PMID- 27614525
TI - [The dawn of radiotherapy, between strokes of genius, dramas and controversies].
AB - Radiotherapy is 120 years old. A few months only after the discoveries of
Roentgen, Becquerel and Marie and Pierre Curie, a few scientists tried to use the
newly discovered rays to treat patients. The question of the name of the first
"radiation therapist" remains debated. Although often proposed, Emil Grubbe from
Chicago seems to have been disqualified. Leopold Freund from Vienna treated a
benign cutaneous lesion. Finally, Victor Despeignes from Lyon appears to be the
most serious candidate, having treated in 1896 a gastric cancer, and obtaining a
very significant tumour regression. The pioneers of radiotherapy paid a heavy
tribute to the development of the specialty; a number of them appears on the -
most probably incomplete - list of 352 names engraved on the monument dedicated
to the "radiation martyrs" in Hamburg. We must keep in mind that it is only
within a few years that a handful of brilliant pioneers built the foundations on
which radiotherapy could emerge.
PMID- 27614524
TI - [Intensity-modulated radiotherapy for head and neck cancer. Dose constraint for
salivary gland and mandible].
AB - Intensity-modulated radiation therapy (IMRT) is the gold standard for head and
neck irradiation. It allows better protection to the organs at risk such as
salivary glands and mandible, and can reduce the frequency of xerostomia, trismus
and osteoradionecrosis. At the time of treatment planning, the mean dose to a
single parotid gland should be kept below 26Gy, the mean dose to a single
submandibular gland below 39Gy, the mean dose to the mandible below 60 to 65Gy
and the D2% to a single temporomandibular joint below 65Gy. These dose
constraints could be further improved with data extracted from cohorts of
patients receiving IMRT exclusively. The dose administered to the target volumes
should not be lessened to spare the salivary glands or mandible.
PMID- 27614526
TI - [Partial breast irradiation technique with external beam radiation therapy and
brachytherapy].
AB - Accelerated Partial Breast Irradiation (APBI) appears to be an efficient
therapeutic modality provided that it uses strict selection criteria and a
reliable and well-managed technique. The techniques that enable to deliver
postoperative APBI are interstitial brachytherapy, endocavitary brachytherapy and
external beam radiation therapy. Once an appropriate selection of the candidates
is made, each radiation technique needs an exact target volume definition and a
strict compliance with its own dosimetric constraints. Results of ongoing
randomized trials should increase our knowledge of all these parameters, and give
us responses about the comparison of the different techniques.
PMID- 27614527
TI - [Radiotherapy in localized stages of follicular and diffuse non-Hodgkin's
lymphomas].
AB - Treatment with monoclonal antibodies, especially rituximab, is more and more
frequent and questions the interest of radiotherapy in limited stages of diffuse
B-cell large cell and follicular non-Hodgkin's lymphomas. From a review of
literature, it appears that radiotherapy is of interest in bulky disease,
patients with incomplete metabolic response, elderly patients receiving short
chemotherapy and those with recurrence after exclusive chemotherapy. Finally,
this article gives recommendations on available techniques of radiotherapy and
doses to be delivered.
PMID- 27614528
TI - [Robust treatment planning in proton therapy].
AB - The concentration of the dose delivered by protons at the end of their path, the
Bragg peak, has the potential to improve external radiotherapy treatments.
Unfortunately, the main strength of the protons, their finite range, is also
their greatest weakness. Any uncertainty on the range may lead to inadequate
target coverage or excessive toxicity. The uncertainties have multiple origins
and include, among others, ballistic errors, morphological modifications or
inaccurate estimations of the physical quantities necessary to predict the proton
range. Uncertainties have been part of daily practice in conventional
radiotherapy with X-rays for a long time. However, dose distributions delivered
with X-rays are much less sensitive to uncertainties than the ones delivered with
protons. This relative insensitivity enabled the management of uncertainties
through safety margins using a simple formalism. The conditions of validity of
this formalism are much more restrictive for proton therapy, leading to the need
of developing new tools and adapted strategies to manage accurately these
uncertainties. The objective of this paper is to present a vision for the
management of uncertainties in proton therapy in the continuity of formalisms
established for X-rays. The latter are first summarized before discussing the
necessary developments in order to consistently apply them to protons.
PMID- 27614529
TI - [Intensity-modulated radiotherapy of head and neck cancers. Dose constraint for
spinal cord and brachial plexus].
AB - Given the ballistic opportunities it offers, intensity-modulated radiotherapy has
emerged as the gold standard treatment for head and neck cancers. Protection of
organs at risk is one of the objectives of optimization during the planning
process. The compliance of dose constraints to the nervous system must be
prioritized over all others. To avoid complications, it is recommended to respect
a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using
conventional fractionation of 2Gy per fraction. These constraints can be adapted
depending on the clinical situation; they will probably be refocused by the
follow-up of the IMRT studies.
PMID- 27614530
TI - Direct-to-consumer teledermatology services for pediatric patients: Room for
improvement.
AB - Direct-to-consumer teledermatology is radically changing the way some patients
obtain dermatologic care. Many direct-to-consumer teledermatology services offer
care to patients younger than 18 years, but policies and standards are
nonuniform. For pediatric patients, direct-to-consumer teledermatology is a
substantial departure from in-person care. More consensus, standards, and
guidelines are necessary.
PMID- 27614531
TI - Remarkable differences in the epidemiology of pemphigus among two ethnic
populations in the same geographic region.
AB - BACKGROUND: The epidemiology of pemphigus in different ethnic populations exposed
to similar environments is unknown. Trends in the incidence of pemphigus based on
an immunopathologically validated cohort have not been investigated. OBJECTIVES:
We sought to estimate the incidence of pemphigus in Israel and to investigate
differences between the 2 major ethnic populations. METHODS: Pemphigus incidence
was retrospectively estimated from January 2000 to December 2015 in 2 Israeli
regions with a total population of 1.56 million inhabitants. RESULTS: One hundred
eighty patients with pemphigus (mean age, 54.70 +/- 16 years) were identified.
The overall estimated incidence was 7.2 per million inhabitants per year (95%
confidence interval, 6.2-8.3). The incidence in the Jewish population was
threefold higher than that in Arabs (9.6 vs 3.2 cases per million per year,
respectively; P < .0001) and higher among women than men (9 vs 5.3 cases per
million per year, respectively; P < .0001). The incidence decreased from 8.4
cases per million per year in 2000 to 2005 to 7.0 and 6.0 (95% confidence
interval, 4.5-7.9) in 2006 to 2010 and 2011 to 2015, respectively (P = .068).
LIMITATIONS: This study was limited by the retrospective design and the small
population. CONCLUSIONS: The incidence of pemphigus in Israel is among the
highest reported worldwide and is significantly more frequent among Jews.
PMID- 27614532
TI - Long-term trend and spatial pattern of PM2.5 induced premature mortality in
China.
AB - With rapid economic growth, China has witnessed increasingly frequent and severe
haze and smog episodes over the past decade, posing serious health impacts to the
Chinese population, especially those in densely populated city clusters.
Quantification of the spatial and temporal variation of health impacts
attributable to ambient fine particulate matter (PM2.5) has important
implications for China's policies on air pollution control. In this study, we
evaluated the spatial distribution of premature deaths in China between 2000 and
2010 attributable to ambient PM2.5 in accord with the Global Burden of Disease
based on a high resolution population density map of China, satellite retrieved
PM2.5 concentrations, and provincial health data. Our results suggest that
China's anthropogenic ambient PM2.5 led to 1,255,400 premature deaths in 2010,
42% higher than the level in 2000. Besides increased PM2.5 concentration, rapid
urbanization has attracted large population migration into the more developed
eastern coastal urban areas, intensifying the overall health impact. In addition,
our analysis implies that health burdens were exacerbated in some developing
inner provinces with high population density (e.g. Henan, Anhui, Sichuan) because
of the relocation of more polluting and resource-intensive industries into these
regions. In order to avoid such national level environmental inequities, China's
regulations on PM2.5 should not be loosened in inner provinces. Furthermore
policies should create incentive mechanisms that can promote transfer of advanced
production and emissions control technologies from the coastal regions to the
interior regions.
PMID- 27614533
TI - [Core values in family medicine revisited].
AB - Family medicine has to continually reinvent itself around a core of values that
constitutes its navigation system. But accurate data on its impact on the health
of people will account for how far the values are actually being implemented.
Thus, we can say that family medicine is a specialty based on values and as well
as evidence based. The absence of a clarification system of values or its
implementation threatens its very existence. Some of the values that are reviewed
have shown great recognition and survival over time. Others are presented because
they seem sufficiently significant. These are: people, comprehensiveness, trust
relationship, patient-centred method, accessibility, continuity, family unity and
the community, teamwork, sustainability of the health system, and continuous
improvement.
PMID- 27614534
TI - [For a qualitatively sound qualitative research in all medical specialties -
Letter on the article "Qualitative research: An opportunity to think again about
evidence-based medicine"].
PMID- 27614535
TI - [Acute aortic syndromes and sleep apnea].
AB - Obstructive sleep apnea (OSA) is a common disease, often present in
"cardiovascular or metabolic patients". OSA favours the occurrence of arterial
lesions, all the more if severe. There is a strong relationship between OSA and
acute aortic syndromes (AAS). This relationship is in part explained by aortic
dilatation linked to OSA. The presence of repeated episodes of sudden variation
of transmural pressure applied on aortic wall seems to play a major role in this
dilatation. All OSA patients should have a search of aortic dilatation by
ultrasound (at a thoracic and abdominal level). Also, screening of OSA should be
systematically performed in patients with aortic disease. The effect of
continuous positive airway pressure in apneic patients with AAS has not been
studied.
PMID- 27614536
TI - Omental ischemia.
AB - Omental ischemia is a rare cause of acute abdomen. Clinical diagnosis is usually
difficult because clinical signs and symptoms are similar to other common causes
of abdominal pain. The most common differential diagnosis is acute appendicitis.
Diagnosis is mainly based on ultrasound, and especially computed tomography scan
analysis. There is, at present, no standard treatment modality for omental
ischemia. When diagnosed by radiological imaging, omental ischemia can be managed
conservatively. We hereby review incidence, etiology, pathology, clinical
presentation, differential diagnosis, biological anomalies, radiological
features, and treatment options of omental ischemia.
PMID- 27614537
TI - 48-Year-Old Woman with Acute-Onset Cough, Chest Tightness, and Shortness of
Breath.
PMID- 27614538
TI - The Inter-rater Reliability of Echocardiographic Diastolic Function Evaluation
Among Emergency Physician Sonographers.
AB - STUDY OBJECTIVES: In a patient with dyspnea and suspected CHF, the evaluation of
diastolic function involves: tissue Doppler of the mitral annulus and 2) pulsed
wave Doppler of the mitral inflow. We aimed to 1) determine the inter-rater
reliability for overall diastolic function and 2) evaluate the reliability of the
individual Doppler measurements. METHODS: A convenience sample of adult emergency
department patients was prospectively enrolled by 8 EPs who had participated in a
1-hour didactic session. Patients were selected if they had a history of CHF or
suspected abnormal diastolic function due to chronic hypertension. Diastolic
function was considered to be abnormal if Tissue Doppler of the septal e' was <8
cm/s and if the lateral e' was <10 cm/s. In cases of discordance, the E/e' ratio
was calculated with <=8 considered normal and >8 considered abnormal. A Kappa
coefficient. Bland-Altman plot and a fixed effect regression model were used in
the analysis. RESULTS: Thirty-two patients were enrolled, and 3 (9.4%) were
excluded due to technical inadequacy. The inter-rater reliability among
sonographers for overall interpretation was very good: kappa = 0.86 (95% CL
[0.67, 1.0]). Based on the Bland-Altman plot, was no consistent bias between
readers. There was no evidence to conclude that the readings differed among
sonographers: septal e' (p = 0.77), lateral e' (p = 0.89) and E (p = 0.15).
CONCLUSION: EP sonographers obtained similar Doppler measurements for diastolic
function evaluation with very good inter-rater reliability for the assessment of
overall diastolic function.
PMID- 27614540
TI - Multi-Society Presidents' Page: The Value of Membership in Your Sub-Specialty
Society.
PMID- 27614539
TI - Clinical Assessment of Medical Students in Emergency Medicine Clerkships: A
Survey of Current Practice.
AB - BACKGROUND: Assessment practices in emergency medicine (EM) clerkships have not
been previously described. Clinical assessment frequently relies on global
ratings of clinical performance, or "shift cards," although these tools have not
been standardized or studied. OBJECTIVE: We sought to characterize assessment
practices in EM clerkships, with particular attention to shift cards. METHODS: A
survey regarding assessment practices was administered to a national sample of EM
clerkship directors (CDs). Descriptive statistics were compiled and regression
analyses were performed. RESULTS: One hundred seventy-two CDs were contacted, and
100 (58%) agreed to participate. The most heavily weighted assessment methods in
final grades were shift cards (66%) and written examinations (21-26%), but there
was considerable variability in grading algorithms. EM faculty (100%) and senior
residents (69%) were most commonly responsible for assessment, and assessors were
often preassigned (71%). Forty-four percent of CDs reported immediate completion
of shift cards, 27% within 1 to 2 days, and 20% within a week. Only 40% reported
return rates >75%. Thirty percent of CDs do not permit students to review
individual evaluations, and 54% of the remainder deidentify evaluations before
student review. Eighty-six percent had never performed psychometric analysis on
their assessment tools. Sixty-five percent of CDs were satisfied with their shift
cards, but 90% supported the development of a national tool. CONCLUSION: There is
substantial variability in assessment practices between EM clerkships, raising
concern regarding the comparability of grades between institutions. CDs rely on
shift cards in grading despite the lack of evidence of validity and inconsistent
process variables. Standardization of assessment practices may improve the
assessment of EM students.
PMID- 27614541
TI - Echocardiographic Assessment of Aortic Pulse-Wave Velocity: Validation against
Invasive Pressure Measurements.
AB - BACKGROUND: Aortic pulse-wave velocity (PWV) is a measure of aortic stiffness
that has a prognostic role in various diseases and in the general population. A
number of methods are used to measure PWV, including Doppler ultrasound. Although
echocardiography has been used for PWV measurement, to the authors' knowledge, it
has never been tested against an invasive reference method at the same time
point. Therefore, the aim of this study was to compare prospectively an
echocardiographic PWV measurement, called echo-PWV, with an invasive study.
METHODS: Forty-five patients (mean age, 66 years; 60% men) underwent simultaneous
intra-arterial pressure recording and echocardiographic Doppler flow evaluation
during elective cardiac catheterization. Proximal pressure and Doppler waveforms
were acquired in the aortic arch. Distal pressure waveforms were registered in
the right and distal Doppler waveforms in the left external iliac artery. Transit
time was measured as a delay of the foot of pressure or Doppler waveform in the
distal relative to the proximal location. Distance was measured on the catheter
for invasive PWV and over the surface for echo-PWV. Echo-PWV was calculated as
distance divided by transit time. RESULTS: In the whole group, mean invasive PWV
was 9.38 m/sec and mean echo-PWV was 9.51 m/sec (P = .78). The Pearson'
correlation coefficient between methods was 0.93 (P < .0001). A Bland-Altman plot
revealed a mean difference between invasive PWV and echo-PWV of 0.13 +/- 0.79
m/sec. CONCLUSIONS: Echo-PWV, based on Doppler echocardiography, is a reliable
method of aortic PWV measurement, with a close correlation with invasive
assessment. Wider implementation of the echo-PWV method for the evaluation of
aortic wall stiffness can further expand the clinical and scientific utility of
echocardiography.
PMID- 27614542
TI - Cumulative Burden of Myocardial Dysfunction in Cardiac Amyloidosis Assessed Using
Four-Chamber Cardiac Strain.
AB - BACKGROUND: The aim of this study was to test the hypothesis that prognosis in
patients with cardiac amyloidosis is closely coupled with amyloid burden in all
four cardiac chambers. The goal was to evaluate longitudinal strain (LS) in each
cardiac chamber and to determine whether LS in specific cardiac chambers is
preferentially associated with prognosis over conventional two-dimensional
echocardiographic parameters in patients with cardiac amyloidosis. METHODS:
Patients with two phenotypes of left ventricular (LV) hypertrophy (cardiac
amyloidosis in 55 patients and nonobstructive hypertrophic cardiomyopathy in 40
patients) and 55 healthy subjects were retrospectively enrolled for the
simultaneous assessment of LS of all four cardiac chambers in the apical four
chamber view. Patients with cardiac amyloidosis were followed up to record major
adverse cardiovascular events, including cardiac death, heart transplantation,
nonfatal myocardial infarction, ventricular tachyarrhythmia, and exacerbation of
heart failure requiring hospitalization. RESULTS: LS in each chamber was
significantly depressed in patients with both LV hypertrophy phenotypes compared
with healthy subjects. Right atrial LS was significantly lower in patients with
cardiac amyloidosis than those with nonobstructive hypertrophic cardiomyopathy
after adjusting for LV ejection fraction and LV mass index. During a median
follow-up period of 10 months, major adverse cardiovascular events developed in
22 patients with cardiac amyloidosis. Four-chamber LS were significantly
associated with major adverse cardiovascular events, with incremental value over
traditional echocardiographic parameters. CONCLUSIONS: Cardiac amyloidosis
involves all cardiac chambers, and thus, chamber-specific strain analysis may be
useful to assess the total cumulative burden of cardiac dysfunction.
PMID- 27614543
TI - Evaluation of the accuracy of a mobile and a stationary system for three
dimensional facial scanning.
AB - PURPOSE: Numerous three-dimensional (3D) facial scanners have emerged on the
market; however, publications evaluating their accuracies are sparse. In this
study, the accuracy of two 3D scanners used in facial scanning was evaluated.
MATERIALS AND METHODS: A test specimen was attached at the right cheek and the
forehead of 41 volunteers. These volunteers were scanned with Artec EVA(r) and
FaceScan3D(r). The acquired data were aligned to a 3D model of the test specimen
for comparing the mean error, original length and width and angles to the
measured values. RESULTS: The mean error in Best Fit alignment is significantly
lower using Artec EVA (p < 0.001) for both test specimens. The deviation from the
original length and width is significantly lower for the test specimens (p <
0.01) when measured with Artec EVA. The aberration of the angles measured between
the front plane and the side plane is significantly lower when measured with
Artec EVA (p < 0.001). Captured with Artec EVA the discrepancy between the
original angle and the angle measured between the side planes to each other is
significantly lower (p < 0.01). CONCLUSIONS: Scanning with Artec EVA leads to
more accurate 3D models as compared to scanning with FaceScan3D. The exactness
achieved by both scanners is comparable to other scanners mentioned in
literature.
PMID- 27614544
TI - Long-term (6.5 years) follow-up of mandibular midline distraction.
AB - To assess the long-term stability and biomechanical effects of mandibular midline
distraction (MMD), a prospective observational study was conducted with a
retrospective cohort. Included were 17 MMD patients, of whom 9 completed the long
term follow-up with a mean of 6.5 years. In all patients, a bone-borne distractor
was used. Dental casts and postero-anterior (PA) cephalograms were taken at fixed
time points: pre-operative (T1), directly post-distraction (T2), 1-year post
operative (T3) and long-term follow-up (T4). Inter canine (ICD), inter first
premolar (IPMD), inter first molar (IMD) distances and arch length (AL) were
measured on dental casts. From the PA cephalograms intercondyle distance (ID) and
the ramal angle (RA) were obtained. A significant and sustained widening was
observed in most measurements. The greatest overall transverse expansion (T1-T4)
occurred in the IPMD (4.1 +/- 0.76 mm, P < 0.05), the ICD, IMD and AL increased,
respectively: 2.0 +/- 0.72 mm, 3.8 +/- 0.82 mm and 3.5 +/- 0.82 mm. The ID did
not change significant (P > 0.05) during all phases of the study. An increase of
RA was observed initially; however, no difference was noted in the long-term.
This study showed that MMD is a stable method to expand the mandible, with no
skeletal effect on the temporomandibular joint.
PMID- 27614545
TI - Five-year speech and language outcomes in children with cleft lip-palate.
AB - OBJECTIVE: To investigate 5-year speech and language outcomes in children with
cleft lip/palate (CLP). MATERIALS AND METHODS: Thirty-eight children aged 4-7
years and 8 months were recruited for this study. Speech abilities including
articulation, resonance, voice, and intelligibility were assessed based on Thai
Universal Parameters of Speech Outcomes. Language ability was assessed by the
Language Screening Test. RESULTS: The findings revealed that children with clefts
had speech and language delay, abnormal understandability, resonance abnormality,
and voice disturbance; articulation defects that were 8.33 (1.75, 22.47), 50.00
(32.92, 67.08), 36.11 (20.82, 53.78), 30.56 (16.35, 48.11), and 94.44 (81.34,
99.32). CONCLUSIONS: Articulation errors were the most common speech and language
defects in children with clefts, followed by abnormal understandability,
resonance abnormality, and voice disturbance. These results should be of critical
concern. Protocol reviewing and early intervention programs are needed for
improved speech outcomes.
PMID- 27614546
TI - An optimised phylogenetic method sheds more light on the main branching events of
rhodopsin-like superfamily.
AB - The comparative genomics between different rhodopsin-like family groups (alpha,
beta, gamma and delta) is not well studied. We used a combination of phylogenetic
analysis and statistical genomic methods to compare rhodopsin-like family
proteins in species likely symbolic of this family's evolutionary progression.
For intra-cluster relationships, we applied mathematical optimisation to enhance
the tree search produced by the neighbour joining method (NJ) and compared it
with maximum likelihood (ML) method. To infer inter-clusters relationships, we
used Needleman-Wunsch analysis (NW), HHsearch, ancestral sequence reconstruction
and phylogenetic network analysis. Using this workflow, we were able to identify
key evolutionary events in the rhodopsin-like family receptors. We found that
alpha rhodopsin-like group gave rise to the beta group, while the gamma rhodopsin
like group diverged from the beta group. We tracked the diversification of every
cluster, revealing that fungal opsin is the most ancient member of the alpha
group, while adenosine receptors could be the first member to diverge in the MECA
(melanocortin, endothelial differentiation sphingolipid, cannabinoid, and
adenosine receptors) subfamily and that histamine receptors could be the parent
of the amines receptors, while hypocretin receptors might be the most ancient
member of the beta group. SOG (somatostatin, opioid, galanin) receptors formed
the most ancient members of the gamma group. Our analysis indicated that basal
receptors might be playing a role in early evolution of the nervous system. This
is evident in Trichoplax adhaerens genome, where we located histamine receptors
and adenosine receptors.
PMID- 27614548
TI - Virtual gaming to develop students' pediatric nursing skills: A usability test.
AB - BACKGROUND: As competition for specialty clinical placements increases, there is
an urgent need to create safe, stimulating, alternative learning environments for
students. OBJECTIVE: To address that clinical gap, our team developed a virtual
game-based simulation to help nursing students develop their pediatric nursing
skills. DESIGN: A usability study was conducted using the Technology Acceptance
Model as a research framework. SETTING AND PARTICIPANTS: The study was conducted
at a community college and included nursing students, nursing faculty/clinicians
and two gaming experts. METHODS: The two experts evaluated the game using a
heuristic checklist after playing the game. Participants engaged in a think-aloud
activity while playing the game and completed a survey and interview based on the
Technology Acceptance Model to explore ease of use and utility of the game.
RESULTS: We found a high degree of user satisfaction with the game. Students
reported that they had learned about pediatric care, they had become immersed in
the game and they were keen to keep playing. Several design changes were
recommended. CONCLUSION: Usability testing is critical in the early stages of
simulation development and the study provided useful direction for the
development team in the next stage of game development.
PMID- 27614547
TI - A behavioral economic analysis of texting while driving: Delay discounting
processes.
AB - The purpose of the present study was to examine an impulsive decision-making
process underlying texting while driving from a behavioral economic perspective.
A sample of 108 college students completed a novel discounting task that
presented participants with a hypothetical scenario in which, after receiving a
text message while driving, they rated the likelihood of replying to a text
message immediately versus waiting to reply for a specific period of time.
Participants also completed a delay discounting task in which they made repeated
hypothetical choices between obtaining a larger amount of money available after a
delay and an equal or lesser amount of money available immediately. The results
show that the duration of the delay is a critical variable that strongly
determines whether participants choose to wait to reply to a text message, and
that the decrease in the likelihood of waiting as a function of delay is best
described by a hyperbolic delay discounting function. The results also show that
participants who self-reported higher frequency of texting while driving
discounted the opportunity to reply to a text message at greater rates, whereas
there was no relation between the rates of discounting of hypothetical monetary
rewards and the frequency of texting while driving. The results support the
conclusion that texting while driving is fundamentally an impulsive choice.
PMID- 27614549
TI - Development of a novel empathy-related video-feedback intervention to improve
empathic accuracy of nursing students: A pilot study.
AB - BACKGROUND: Stressed family carers engage in health-risk behaviours that can lead
to chronic illness. Innovative strategies are required to bolster empathic
dialogue skills that impact nursing student confidence and sensitivity in meeting
carers' wellness needs. PURPOSE: To report on the development and evaluation of a
promising empathy-related video-feedback intervention and its impact on student
empathic accuracy on carer health risk behaviours. DESIGN: A pilot quasi
experimental design study with eight pairs of 3rd year undergraduate nursing
students and carers. METHODS: Students participated in perspective-taking
instructional and practice sessions, and a 10-minute video-recorded dialogue with
carers followed by a video-tagging task. Quantitative and qualitative approaches
helped us to evaluate the recruitment protocol, capture participant responses to
the intervention and study tools, and develop a tool to assess student empathic
accuracy. MAIN RESULTS: The instructional and practice sessions increased student
self-awareness of biases and interest in learning empathy by video-tagging
feedback. Carers felt that students were 'non-judgmental', inquisitive, and
helped them to 'gain new insights' that fostered ownership to change their health
risk behaviour. There was substantial Fleiss Kappa agreement among four raters
across five dyads and 67 tagged instances. CONCLUSION: In general, students and
carers evaluated the intervention favourably. The results suggest areas of
improvement to the recruitment protocol, perspective-taking instructions, video
tagging task, and empathic accuracy tool.
PMID- 27614550
TI - Corrigendum to "PGC-1alpha ameliorates AngiotensinII-induced eNOS dysfunction in
human aortic endothelial cells" [Vasc. Pharmacol. 83 (2016) 90-97].
PMID- 27614551
TI - Ultrasound Characteristics of Calf Deep Vein Thrombosis and Residual Vein
Obstruction After Low Molecular Weight Heparin Treatment.
AB - OBJECTIVE/BACKGROUND: Calf deep vein thrombosis (CDVT) is frequently found in
symptomatic outpatients, but CDVT ultrasound diagnostic criteria are still
debated. It has been proposed that only clots with >=5 mm maximum diameter can be
considered as CDVT. AIMS: To assess clot diameters and characteristics of CDVT,
and to assess the recanalization rate of CDVT after anticoagulant treatment.
METHODS: In a prospective, multicenter cohort study symptomatic outpatients in
whom CDVT was diagnosed by ultrasound were enrolled. Posterior tibial, fibular,
medial and lateral gastrocnemius, and soleal veins were compressed transversally
over their entire length. Clot diameter was measured during maximum compression
and ultrasound was repeated after 6 weeks of low molecular weight heparin
treatment. RESULTS: In 172 patients (age 70 +/- 1 y, male 32%) CDVT was detected
in 132 (76.7%) muscle veins only, and in 24 (14%) axial veins only, while 16
(9.3%) patients had both muscular and axial CDVT. A total of 212 clots were found
with a diameter of 5.8 +/- 1.8 mm (IQR 4.5-6.8 mm) with the 10th percentile being
>=3.5 mm. A cut off value of >=5 mm had a sensitivity of 0.76 (95% CI 0.69-0.82),
whereas a value of >=3.5 mm had a sensitivity of 0.94 (95% CI 0.89-0.97).
Recanalization (i.e. residual vein obstruction <=2 mm) was found in 51% of
patients and the recanalization rate was not correlated with clot diameter at
enrolment (rho -0.128 p = 0.93) or with type of CDVT (axial vs. muscular
thrombosis). Patients with significantly reduced mobility had lower probability
of CDVT recanalization. CONCLUSION: A clot diameter >=5 mm is found in only 76%
of CDVT patients and a clot diameter >=3.5 mm may be more appropriate as a
threshold for CDVT. After 6 weeks of anticoagulant treatment, half of CDVT
patients had recanalization and recanalization was not correlated with clot
characteristics at enrolment, but with mobility of the patients.
PMID- 27614552
TI - Re: 'Comparison of Total Arch and Partial Arch Transposition During Hybrid
Endovascular Repair for Aortic Arch Disease'.
PMID- 27614553
TI - Late Fate of Cryopreserved Arterial Allografts.
AB - OBJECTIVE: Initial enthusiasm for use of cryopreserved arterial allografts was
subsequently tempered by suboptimal long-term outcome. Thrombosis, anastomotic
pseudo-aneurysm, allograft disruption, aneurysmal degeneration, recurrent
intestinal fistulization, and persistent infection are commonly reported in
series with long-term follow-up. The authors reviewed their experience over the
past 15 years with the use of cryopreserved arterial allografts as a vascular
substitute for vascular prosthetic infection or for primary arterial infection,
to investigate allograft-related complications. MATERIAL AND METHODS: A
retrospective analysis of prospectively collected data was conducted for 103
cryopreserved arterial allografts inserted in 96 patients between July 2000 and
July 2015. There were 78 patients with infected vascular prosthesis (IVP), nine
patients with an aorto-enteric fistula (AEF), and nine patients with primary
arterial infection (PAI). RESULTS: The in-hospital mortality was eight out of 78
(9%) IVP patients, three out of nine AEF patients, and zero out of nine PAI
patients. Median follow-up was 49 months. Allograft-related re-interventions were
necessary in 29% of the patients with IVP and four of the patients with AEF, but
none of the patients with PAI. Five-year survival for the IVP, AEF, and PAI
patients was 53%, 44%, and 90%, respectively. CONCLUSION: This series highlights
some shortcomings of cryopreserved arterial allografts in the long term,
including suboptimal outcome-results and shortage of material. The authors
discuss the allograft-related complications and suggest some tricks to minimize
their risk.
PMID- 27614554
TI - Thrombosed Dialysis Access Graft - But Still Functioning.
PMID- 27614555
TI - Monitoring of Foot Oxygenation with Near-infrared Spectroscopy in Patients with
Critical Limb Ischemia Undergoing Percutaneous Transluminal Angioplasty: A Pilot
Study.
AB - OBJECTIVE: Near-infrared spectroscopy (NIRS) non-invasively determines tissue
oxygen saturation (Sto2) in muscle tissue. Its application to monitor real time
hemodynamic changes during percutaneous transluminal angioplasty (PTA) and Sto2
changes in feet 4 weeks after PTA was evaluated. METHODS: This study included 14
patients with critical limb ischemia (CLI, six patients Rutherford classification
Stage IV, two patients Stage V, and six patients Stage VI). In patients with
arterial ulcers, NIRS optodes were placed near the ulcer of the diseased foot
(Optode 1), and at the same spot at the contralateral foot (Optode 2). In
patients without arterial ulcers, Optode 1 was placed on the dorsum of the
diseased foot, and Optode 2 was placed on the dorsum of the contralateral foot.
Single Sto2 values, ankle brachial indices, and toe brachial indices were
obtained at rest before the start of endovascular revascularization and 4 weeks
after treatment. During the endovascular procedure, continuous Sto2 measurements
were recorded throughout the intervention. Completion angiograms were used to
evaluate the success of intervention. RESULTS: Patients underwent treatment of
the superficial femoral artery (79%), popliteal artery (21%), and below the knee
arteries (43%). In 13 of the 14 patients, completion angiograms showed successful
treatment of target lesions. Ankle brachial indices and toe brachial indices
significantly increased 4 weeks after treatment (both p < .01). Single Sto2
values of Optode 1 also significantly increased four weeks after treatment (p <
.01). In contrast, single Sto2 values of Optode 2 did not (p = .73). During the
endovascular procedure, continuous Sto2 measurements of Optode 1 and 2 did not
increase (p = .80, and p = .61, respectively). CONCLUSIONS: NIRS monitoring of
foot oxygenation in patients undergoing endovascular revascularization is safe
and feasible. NIRS is a promising non-invasive technique to monitor hemodynamic
changes in the feet of CLI patients after endovascular treatment using single
Sto2 values.
PMID- 27614556
TI - Orthogonal Rings, Fiducial Markers, and Overlay Accuracy When Image Fusion is
Used for EVAR Guidance.
AB - OBJECTIVE: Evaluation of orthogonal rings, fiducial markers, and overlay accuracy
when image fusion is used for endovascular aortic repair (EVAR). METHODS: This
was a prospective single centre study. In 19 patients undergoing standard EVAR,
3D image fusion was used for intra-operative guidance. Renal arteries and
targeted stent graft positions were marked with rings orthogonal to the
respective centre lines from pre-operative computed tomography (CT). Radiopaque
reference objects attached to the back of the patient were used as fiducial
markers to detect patient movement intra-operatively. Automatic 3D-3D
registration of the pre-operative CT with an intra-operative cone beam computed
tomography (CBCT) as well as 3D-3D registration after manual alignment of nearby
vertebrae were evaluated. Registration was defined as being sufficient for EVAR
guidance if the deviation of the origin of the lower renal artery was less than 3
mm. For final overlay registration, the renal arteries were manually aligned
using aortic calcification and vessel outlines. The accuracy of the overlay
before stent graft deployment was evaluated using digital subtraction angiography
(DSA) as direct comparison. RESULTS: Fiducial markers helped in detecting
misalignment caused by patient movement during the procedure. Use of automatic
intensity based registration alone was insufficient for EVAR guidance. Manual
registration based on vertebrae L1-L2 was sufficient in 7/19 patients (37%).
Using the final adjusted registration as overlay, the median alignment error of
the lower renal artery marking at pre-deployment DSA was 2 mm (0-5) sideways and
2 mm (0-9) longitudinally, mostly in a caudal direction. CONCLUSION: 3D image
fusion can facilitate intra-operative guidance during EVAR. Orthogonal rings and
fiducial markers are useful for visualization and overlay correction. However,
the accuracy of the overlaid 3D image is not always ideal and further technical
development is needed.
PMID- 27614557
TI - Effects of contaminated soil on the growth performance of young Salix (Salix
schwerinii E. L. Wolf) and the potential for phytoremediation of heavy metals.
AB - Salix schwerinii was tested in a pot experiment to assess plant growth
performance i.e., relative height and dry biomass and the potential for heavy
metal uptake in soils polluted with chromium, zinc, copper, nickel and total
petroleum hydrocarbons. The soil used in the pot experiment was collected from a
landfill area in Finland. Peat soil was added at different quantities to the
polluted soil to stimulate plant growth. The plants were irrigated with tap water
or processed water (municipal waste water) to further investigate the effects of
nutrient loading on plant biomass growth. The soil was treated at two pH levels
(4 and 6). The results showed that the addition of 40-70% peat soil at pH 6 to a
polluted soil, and irrigation with processed water accelerated plant growth and
phytoextraction efficiency. In the pot experiment, Salix grown in chromium, zinc,
copper, nickel and total petroleum hydrocarbons -contaminated field soil for 141
days were unaffected by the contaminated soil and took up excess nutrients from
the soil and water. Total mean chromium concentration in the plant organs ranged
from 17.05 to 250.45 mg kg-1, mean zinc concentration ranged from 142.32 to
1616.59 mg kg-1, mean copper concentration ranged from 12.11 to 223.74 mg kg-1
and mean nickel concentration ranged from 10.11 to 75.90 mg kg-1. Mean chromium
concentration in the plant organs ranged from 46 to 94%, mean zinc concentration
ranged from 44 to 76%, mean copper concentration ranged from 19 to 54% and mean
nickel concentration ranged from 8 to 21% across all treatments. Under the
different treatments, chromium was taken up by Salix in the largest quantities,
followed by zinc, copper and nickel respectively. Salix also produced a moderate
reduction in total petroleum total petroleum hydrocarbons in the polluted soil.
The results from the pot experiment suggest that Salix schwerinii has the
potential to accumulate significant amounts of chromium, zinc, copper and nickel.
However, long term research is needed to verify the phytoextraction abilities of
Salix observed in the pot experiment.
PMID- 27614558
TI - Lead Extraction for Treatment of Cardiac Device Infection: A 20-Year Single
Centre Experience.
AB - BACKGROUND: Infection is one of the most feared complications of cardiac
implantable electronic devices. We report microbiology, antimicrobial therapy and
infection recurrence in patients with cardiac device infection (CDI) treated with
transvenous lead extraction (TLE) at a single centre over a 20-year period.
METHODS: We identified a cohort of consecutive patients undergoing TLE for CDI by
a single operator at a single high volume centre. Retrospective analysis of
patient characteristics, microbiology, outcomes and infection recurrence was
performed. RESULTS: Between May 1992 to March 2012, 348 patients underwent
extraction due to localised or systemic infection. Seven hundred and twenty leads
were extracted from these patients. The mean follow-up was 5.5+/-4.9 years.
Staphylococcal species accounted for 81% of CDI. A difference is seen in
infection onset for device revision compared with initial implants [median 10
months vs 24 months, P=0.0001]. Duration of antibiotics therapy depended on the
nature of the CDI (21 days post TLE for systemic vs. 10 days for localised
infection, P < 0.0001). There was comparable mortality in the 37 (11.2%) patients
who did not have a replacement device compared with a replacement (30% vs 29%,
P=0.9). Retained lead fragments are a risk factor for CDI recurrence (20.8%
recurrence in retained fragments vs 4.3% in complete removal, P=0.006).
CONCLUSION: Cardiac device infection can be successfully treated with a
combination of TLE and antibiotic therapy. Device therapy can be safely withdrawn
in some patients. Retained lead fragments are a risk factor for recurrent CDI
following extraction.
PMID- 27614559
TI - The Beneficial Effects of Cardiac Rehabilitation on the Function and Levels of
Endothelial Progenitor Cells.
AB - Cardiac rehabilitation (CR) is a comprehensive program, which mainly focusses on
exercise training, disease evaluation, cardiovascular risk factors control,
medication therapy, psychosocial intervention, and patient education. Although
the beneficial properties of CR have been widely evidenced, its mechanism is
still not completely clarified. To date, endothelial progenitor cells (EPCs) have
been explored by emerging studies, and evidence has suggested that CR, especially
exercise training, significantly increases the function and levels of EPCs, which
is likely to elucidate the profiting mechanism of CR. Thus, this review
summarises the potential relationship between CR and EPCs with an aim of
providing novel directions for future CR research.
PMID- 27614560
TI - Seabed litter composition, distribution and sources in the Northern and Central
Adriatic Sea (Mediterranean).
AB - Detecting the origin of marine benthic litter is fundamental for developing
policies aimed at achieving the Good Environmental Status in European Seas by
2020, as requested by the Marine Strategy Framework Directive (MSFD). The
abundance and composition of benthic litter in the Northern and Central Adriatic
Sea were investigated at 67 stations with bottom trawl nets. Average density of
benthic litter was 913+/-80items/km2, ranking the Adriatic as one of the most
polluted basins worldwide. Plastic was dominant in terms of numbers (80%) and
weight (62%), and mainly consisted in bags, sheets and mussel nets. Higher
quantities of litter were found in coastal areas, especially in front river
mouths, coastal cities and mussel farms. In deep waters, litter hotspots were
associated with most congested shipping lanes, indicating an additional litter
input to the basin. Benthic litter composition resulted to be largely driven by
the vicinity to local sources, i.e. mussel farming installations and most
congested shipping routes. These findings provide useful insights to set measures
to manage marine litter in the Adriatic region, and possibly to minimize this
anthropogenic pollution.
PMID- 27614561
TI - Agrochemical characterization of vermicomposts produced from residues of Palo
Santo (Bursera graveolens) essential oil extraction.
AB - Fruits of Palo Santo (Bursera graveolens) are used for essential oil extraction.
The extraction process is very efficient, because up to 3% of the fresh fruits
can be transformed into essential oil; however, a considerable amount of waste is
concurrently produced (>97% of the fresh biomass). Recent developments in
Ecuadorian policies to foster environmentally friendly agroforestry and
industrial practices have led to widespread interest in reusing the waste. This
study evaluated the application of four vermicomposts (VMs), which are produced
from the waste of the Palo Santo fruit distillation in combination with other raw
materials (kitchen leftovers, pig manure, goat manure, and King Grass), for
agrochemical use and for carbon (C) and nitrogen (N) decomposition in two soils
with different textures. The results showed that the vermicompost mixtures (VMM)
were valuable for agricultural utilisation, because total N (min. 2.63%) was
relatively high and the C/N ratio (max. 13.3), as well as the lignin (max. 3.8%)
and polyphenol (max. 1.6%) contents were low. In addition, N availability
increased for both soil types after the application of the VMM. In contrast, N
became immobile during decomposition if the VM of the pure waste was added. This
likely occurred because of the relatively low total N (1.16%) content and high
C/N ratio (35.0). However, the comparatively low C decomposition of this VM type
makes its application highly recommendable as a strategy to increase the levels
of organic matter and C, as well as for soil reclamation. Overall, these results
suggest that the residues of the Palo Santo essential oil extraction are a
potential source for vermicompost production and sustainable agriculture.
PMID- 27614562
TI - A standardized method for sampling and extraction methods for quantifying
microplastics in beach sand.
AB - Microplastics are ubiquitous in the environment, are frequently ingested by
organisms, and may potentially cause harm. A range of studies have found
significant levels of microplastics in beach sand. However, there is a
considerable amount of methodological variability among these studies.
Methodological variation currently limits comparisons as there is no standard
procedure for sampling or extraction of microplastics. We identify key sampling
and extraction procedures across the literature through a detailed review. We
find that sampling depth, sampling location, number of repeat extractions, and
settling times are the critical parameters of variation. Next, using a case-study
we determine whether and to what extent these differences impact study outcomes.
By investigating the common practices identified in the literature with the case
study, we provide a standard operating procedure for sampling and extracting
microplastics from beach sand.
PMID- 27614563
TI - Benthic surveys of the historic pearl oyster beds of Qatar reveal a dramatic
ecological change.
AB - The study aimed to confirm the presence of historic oyster banks of Qatar and
code the biotopes present. The research also collated historical records and
scientific publications to create a timeline of fishery activity. The oyster
banks where once an extremely productive economic resource however, intense
overfishing, extreme environmental conditions and anthropogenic impacts caused a
fishery collapse. The timeline highlighted the vulnerability of ecosystem
engineering bivalves if overexploited. The current status of the oyster banks
meant only one site could be described as oyster dominant. This was unexpected as
the sites were located in areas which once supported a highly productive oyster
fishery. The research revealed the devastating effect that anthropogenic impacts
can have on a relatively robust marine habitat like an oyster bed and it is hoped
these findings will act as a driver to investigate and map other vulnerable
habitats within the region before they too become compromised.
PMID- 27614564
TI - Inter-annual changes in fish communities of a tropical bay in southeastern
Brazil: What can be inferred from anthropogenic activities?
AB - We assessed inter-annual changes in fish assemblages of a tropical bay which
experienced a heavily industrialized process in the last decades. A highly
significant difference in community structure among the bay zones, and a decrease
in fish richness and abundance over time were found. Changes in fish richness and
abundance between the two first (1987-1988 and 1993-1995) and the two latter time
periods (1998-2001 and 2012-2013) were sharpest in the inner bay zone, the most
impacted bay area, and in the middle zone, whereas the outer zone remained
comparatively stable over time. These changes coincided with increased metal
pollution (mainly, Zn and Cd) in the bay and with the enlargement of the Sepetiba
Port. Spatial changes in the fish community structure among the bay zones were
related to differences in salinity, transparency and depth with this latter
variable acting as a buffer stabilizing temporal community changes.
PMID- 27614565
TI - Phosphorus release from coastal sediments: Impacts of the oxidation-reduction
potential and sulfide.
AB - The release of phosphorus (P) from benthic sediments can affect the P content,
nutrient status and quality of overlying waters in coastal ecosystem. This study
was carried out to investigate the influence of oxidation-reduction potential
(ORP) and sulfide on P release from sediments in the coastal estuary of the
Yuniao River, China. The results showed that ferric iron-bound P was the main P
burial phase in the sediments. The P concentration in overlying water increased
with ORP decrease and sulfide increase, displaying a significant linear
correlation with the ORP and sulfide concentration. The results indicate that
decreased ORP may elevate the zero equilibrium phosphorus concentration,
enhancing the capability of P release. And increased sulfide may react or capture
reactive iron in sediments, reducing the P adsorption capacity and accelerating P
release. Therefore, the control of ORP and sulfide production is important in the
sink/source conversion of P in coastal sediments.
PMID- 27614566
TI - Microplastics in tourist beaches of Huatulco Bay, Pacific coast of southern
Mexico.
AB - The presence and impacts of plastic marine debris (PMD) have been documented in
the oceans worldwide, and they deserve special attention. This study is the first
to report the presence of microplastics in tourist beaches located in Huatulco
Bay, southern Mexico. A total of 70 beach sediment samples (for 2 distinct
seasons) were collected from Huatulco Bay in April 2013 and December 2014. The
samples were subsequently extracted by scanning electron microscopy (SEM) to
identify the fibrous microplastics (diameter<5mm). The maximum number of fibrous
materials was found in April 2013 and December 2014 in the Rincon Sabroso beach
(48/30g sediment) and the Cuatunalco beach (69/30g sediment), respectively.
Overall, a high amount of microplastics is present in the Conejos, Tangolunda,
Santa Cruz, and San Agustin beaches. The microplastics are mainly derived from
tourism-based activities and effluents discharged from the hotels and restaurants
located along the beaches.
PMID- 27614567
TI - Dissolved trace elements in a nitrogen-polluted river near to the Liaodong Bay in
Northeast China.
AB - Dissolved trace element concentrations (Ba, Fe, Mn, Si, Sr, and Zn) were
investigated in the Haicheng River near to the Liaodong Bay in Northeast China
during 2010. Dissolved Ba, Fe, Mn, and Sr showed significant spatial variation,
whereas dissolved Fe, Mn, and Zn displayed seasonal variations. Conditions such
as water temperature, pH, and dissolved oxygen were found to have an important
impact on redox reactions involving dissolved Ba, Fe, and Zn. Dissolved Fe and Mn
concentrations were regulated by adsorption or desorption of Fe/Mn oxyhydroxides
and the effects of organic carbon complexation on dissolved Ba and Sr were found
to be significant. The sources of dissolved trace elements were found to be
mainly from domestic sewage, industrial waste, agricultural surface runoff, and
natural origin, with estimated seasonal and annual river fluxes established as
important inputs of dissolved trace elements from the Haicheng River into the
Liaodong Bay or Bohai Sea.
PMID- 27614568
TI - Violent behavior and aggression in schizophrenia: Prevalence and risk factors. A
multicentric study from three Latin-America countries.
AB - OBJECTIVE: The aim of the present study was (i) to assess the prevalence of
Violent Behavior in Schizophrenia (VBS) in a sample of community-dwelling
outpatients in three middle-income countries of Latin America and (ii) to
determine the clinical and socio-demographical risk factors associated with VBS
and aggression level. METHODS: The study included 253 stabilized outpatients with
schizophrenia and their principal caregivers from 3 public ambulatory psychiatric
care centers in Bolivia (N=83), Chile (N=85), and Peru (N=85). VBS was defined
according to the Overt Aggression Scale (OAS) score and the aggression level was
measured by the aggression subscore of the Agitated Behavior Scale of Corrigan.
We collected socio-demographic information and clinical data. Multiple linear and
logistic regressions were performed to determine which variables were associated
with VBS and aggression level. RESULTS: The prevalence of VBS differed
statistically between the three countries (p<0.001) with 3.5% in Chile, 14.6% in
Peru and 55.4% in Bolivia. After adjustment for confounding factors, VBS was
associated with a younger age, a more severe psychotic symptomatology, a lower
family income and unemployment. After adjustment for confounding factors,
aggression level was associated with a more severe psychotic symptomatology, a
lower family income, a younger age at illness onset and higher number of
hospitalizations in the last 3years. CONCLUSION: These results may guide future
health policies to specifically provide social support and rehabilitation care to
VBS patients in middle-income countries, including psychoeducation and a more
integrated work between the treating medical team and the social workers.
PMID- 27614569
TI - Routine data linkage to identify and monitor diabetes in clozapine-treated
patients with schizophrenia.
PMID- 27614571
TI - Corrigendum to "Dabigatran in clinical practice: Contemporary overview of the
evidence" [Int. J. Cardiol. 220 (2016) 417-428].
PMID- 27614570
TI - Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7.
AB - Viral infections during fetal and adolescent periods, as well as during the
course of schizophrenia itself have been linked to the onset and/or relapse of a
psychosis. We previously reported that the unique antipsychotic aripiprazole, a
partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-alpha
from interferon-gamma-activated rodent microglial cells. Polyinosinic
polycytidylic acid (polyI:C) has recently been used as a standard model of viral
infections, and recent in vitro studies have shown that microglia are activated
by polyI:C. Aripiprazole has been reported to ameliorate behavioral abnormalities
in polyI:C-induced mice. To clarify the anti-inflammatory properties of
aripiprazole, we investigated the effects of aripiprazole on polyI:C-induced
microglial activation in a cellular model of murine microglial cells and possible
surrogate cells for human microglia. PolyI:C treatment of murine microglial cells
activated the production of TNF-alpha and enhanced the p38 mitogen-activated
protein kinase (MAPK) pathway, whereas aripiprazole inhibited these responses. In
addition, polyI:C treatment of possible surrogate cells for human microglia
markedly increased TNF-alpha mRNA expression in cells from three healthy
volunteers. Aripiprazole inhibited this increase in cells from two individuals.
PolyI:C consistently increased intracellular Ca2+ concentration ([Ca2+]i) in
murine microglial cells by influx of extracellular Ca2+. We demonstrated that
transient receptor potential in melastatin 7 (TRPM7) channels contributed to this
polyI:C-induced increase in [Ca2+]i. Taken together, these data suggest that
aripiprazole may be therapeutic for schizophrenia by reducing microglial
inflammatory reactions, and TRPM7 may be a novel therapeutic target for
schizophrenia. Further studies are needed to validate these findings.
PMID- 27614572
TI - Corrigendum to "Addition of ivabradine to betablockers in patients with atrial
fibrillation: Effects on heart rate and exercise tolerance" [Int. J. Cardiol. 202
(2016) 76-77].
PMID- 27614573
TI - Effective cauda equina decompression in two siblings with Charcot-Marie-Tooth
disease type 1B.
AB - Two siblings with Charcot-Marie-Tooth (CMT) 1B due to a c.517G>C (p.Gly173Arg)
mutation in the MPZ gene both developed an acute cauda syndrome with unbearable
back pain radiating to both legs, progressive muscle weakness of the legs, and
saddle hypesthesia with fecal and urinary incontinence. MRI showed in both
patients a lumbar spinal canal totally filled with hypertrophic caudal nerve
roots. We performed acute decompression. Postoperatively, in both patients, the
back pain resolved immediately, there was a significant improvement of both the
paresis of the legs and the hypesthesia, and there was a full return of
continence. There was no recurrence of acute symptoms during respectively 19
years and 1.5 years of follow-up. We conclude that in patients with CMT and a
related cauda syndrome because of hypertrophic caudal nerve roots, acute
decompression can be an effective and safe treatment with long-term efficacy.
PMID- 27614574
TI - Reduced neuronal density in the CA1 anterodorsal hippocampus of the mdx mouse.
AB - Duchenne muscular dystrophy (DMD) is associated with non-progressive cognitive
dysfunction including hippocampal-dependent memory deficits. Loss of the
cytoskeleton-associated dystrophin protein in central inhibitory synapses,
associated with consequent alterations in GABAergic function and synaptic
plasticity, has been proposed as a primary mechanism responsible for cognitive
impairments. However, several lines of evidence suggest a multifactorial etiology
involving alternative signaling pathways, some of which could affect neuronal
survival. To determine whether changes in neuronal density in the hippocampus
could contribute to the emergence of memory deficits, we undertook an unbiased
stereological estimation of neuron number in the anterodorsal CA1 region of the
hippocampus of the dystrophin-deficient mdx mouse model of DMD. We found a
significant reduction (~34%) in the number of pyramidal neurons, with a
heterogeneous magnitude of genotype differences along the hippocampal antero
posterior axis. This extends previous knowledge of brain morphofunctional
alterations induced by dystrophin loss and suggests that putative mechanisms
involved in neurogenesis and/or neuron survival might contribute to the emergence
of hippocampal-dependent learning and memory deficits in DMD.
PMID- 27614575
TI - Myotonia congenita type Becker in Bulgaria: First genetically proven cases and
mutation screening of two presumable endemic regions.
AB - Myotonia congenita type Becker is an autosomal recessive nondystrophic skeletal
muscle disorder, caused by mutations in the CLCN1 gene. The disease is
characterized by muscle stiffness and an inability of the muscle to relax after
voluntary contraction. Here we report the results from molecular genetic testing
of 6 families, referred for sequencing of the CLCN1 gene. The disease causing
mutations were detected in 5 of the cases, representing diverse type of
nucleotide changes: nonsense (p.Arg894*), splice-site (c.1471+1G>A), missense
(p.Val273Met; p.Tyr524Cys). Two additional changes were detected in an
asymptomatic individual (c.2284+5C>T and p.Phe167Leu). Two of the detected
mutations are interesting from population point of view. The novel missense
mutation p.Tyr524Cys was found in a large Bulgarian family with affected
individuals in both vertical and horizontal pedigree directions, all of them
carrying the mutation in homozygous form. They populate a village located in the
northwest part of the country. Endogamous marriages are very unusual for the
Bulgarian population, supposing a high carrier frequency in this subpopulation.
Screening of 154 residents of the corresponding region showed a significant
carrier frequency for the p.Tyr524Cys mutation of about 0.65% (1/154). The second
interesting region in the context of Myotonia congenita type Becker is the
southwest part of the country, where we found a large family of Bulgarian Turkish
origin. The disease causing missense mutation p.Val273Met was again present in
homozygous state. Surprisingly, the genetic testing of newborns from southwest
Bulgaria showed an even higher carrier status of about 2.6% (3/116), disproving
our initial hypothesis of endogamous marriages (traditionally common in this
subpopulation) being the cause of the disease in these patients. However the
probability of consanguineous marriages being the cause for further exaggeration
of the anyway very high carrier frequency cannot be excluded.
PMID- 27614576
TI - Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne
muscular dystrophy.
AB - Osteoporosis is a major problem in boys with Duchenne Muscular Dystrophy (DMD),
attributable to muscle weakness and glucocorticoid therapy. Consensus regarding
bone health assessment and management is lacking. Lumbar spine areal bone mineral
density (defined as bone mass per area of bone) by dual-energy X-ray
absorptiometry (DXA) is frequently the primary measure used, but has limitations
for boys with DMD. We retrospectively studied 292 ambulant glucocorticoid-treated
boys with DMD categorized by functional mobility score, FMS 1, 2 or 3. We
assessed DXA whole body and lumbar spine areal bone mineral density and content Z
scores adjusted for age and height, lateral distal femur areal bone mineral
density Z-scores, frequency of fractures, and osteoporosis by International
Society for Clinical Densitometry 2013 criteria. Whole body and femoral DXA
indices decreased, while spine fractures increased, with declining motor
function. Lumbar spine areal bone mineral density Z-scores appeared to improve
with declining motor function. Bone mineral content Z-scores were consistently
lower than corresponding bone mineral density Z-scores. Our findings highlight
the complexity of assessing bone health in boys with DMD. Bone health indices
worsened with declining motor function in ambulant boys, but interpretation was
affected by measure and skeletal site examined. Whole body bone mineral content
may be a valuable measure in boys with DMD. Lumbar spine areal bone mineral
density Z-score as an isolated measure could be misleading. Comprehensive
management of osteoporosis in boys with DMD should include vertebral fracture
assessment.
PMID- 27614577
TI - Probable case of spotted fever group rickettsial infection in a new suspected
endemic area, Colombia.
AB - Spoted fever group (SFG) rickettsioses are actually considered as emerging and re
emerging zoonotic diseases, caused by pathogenic bacteria of the spotted fever
group rickettsiae (SFGR). Recently, serologic studies in human and animals
conducted in Colombian Orinoquia, showed a high seroprevalence against SFGR. In
June 2015, a 50-year-old male was admitted to a hospital in Bogota, Colombia,
with two days of malaise and temperature of 39 degrees C, associated to
generalized rash 24h after the onset of fever. He referred a work visit and
outdoor activities in rural area of the Department of Meta 15days prior the onset
of symptoms. The patient was transferred to the intensive care unit with
supplementary oxygen, inotropic support and was assessed by the infectious
diseases department, indicating the addition of Doxycycline. After seven days of
antibiotic treatment the patient was discharged with no evidence of new symptoms
or sequels. Retrospectively, two serum samples collected during the acute and
convalescent phase were evaluated; there was four fold rise in titer against
SFGR. With the foregoing, associated with the recent serological evidence that
suggests the circulation of SFGR species in the Colombian Orinoquia, we consider
to recognize this region as a new endemic area for SFG Rickettsioses.
PMID- 27614578
TI - Effects of high organic load on amoA and nirS gene diversity of an intermittently
aerated and fed membrane bioreactor treating landfill leachate.
AB - The effects of external carbon source addition on the nitrification and
denitrification process were investigated in an intermittently aerated and fed
membrane bioreactor treating landfill leachate by recording system performance,
and amoA and nirS diversity dynamics using pyrosequencing. By adding 950mg/L
glycerol, denitrification was optimized, resulting in total nitrogen removal
efficiency of 81.0+/-2.4%. Under these conditions, amoA diversity was dominated
by genotypes related to Nitrosomonas europaea, while increase in leachate's
content and in glycerol addition by 50% led to irreversible inhibition of
nitrification and enhanced ammonia accumulation, causing a severe suppression of
Nitrosomonas and an increase in the relative abundance of Nitrosospira. However,
this increase not only affected ammonia oxidizers, but also caused a massive
shift in denitrifying community structure, resulting in the suppression of
Arenimonas metalli-, Candidatus Accumulibacter- and Sulfuritalea hydrogenivorans
nirS related genotypes and the predominance of nirS-associated with Acidovorax
and Thaurea sp.
PMID- 27614579
TI - A novel high-throughput multi-parameter flow cytometry based method for
monitoring and rapid characterization of microbiome dynamics in anaerobic
systems.
AB - A novel multidimensional flow cytometry based method has been demonstrated to
monitor and rapidly characterize the dynamics of the complex anaerobic microbiome
associated with perturbations in external environmental factors. While community
fingerprinting provides an estimate of the meta genomic structure, flow cytometry
provides a fingerprint of the community morphology including its autofluorescence
spectrum in a high-throughput manner. Using anaerobic microbial consortia
perturbed with the controlled addition of various carbon sources, it is possible
to quantitatively discriminate between divergent microbiome analogous to
community fingerprinting techniques using automated ribosomal intergenic spacer
analysis (ARISA). The utility of flow cytometry based method has also been
demonstrated in a fully functional industry scale anaerobic digester to
distinguish between microbiome composition caused by varying hydraulic retention
time (HRT). This approach exploits the rich multidimensional information from
flow cytometry for rapid characterization of the dynamics of microbial
communities.
PMID- 27614580
TI - Analysis and modelling of predation on biofilm activated sludge process:
Influence on microbial distribution, sludge production and nutrient dosage.
AB - The influence of predation on the biofilm activated sludge (BAS) process is
studied using a unified model that incorporates hydrolysis and predation
phenomena into the two stages of the BAS system: moving bed biofilm reactor pre
treatment (bacterial-predator stage) and activated sludge (predator stage). The
unified model adequately describes the experimental results obtained in a
cellulose and viscose full-scale wastewater plant and has been used to evaluate
the role and contribution of predator microorganisms towards removal of COD,
nutrient requirements, sludge production and microbial distribution. The results
indicate that predation is the main factor responsible for the reduction of both
nutrient requirements and sludge production. Furthermore, increasing the sludge
retention time (SRT) does not influence the total biomass content in the AS
reactor of a BAS process in two different industrial wastewater treatments.
PMID- 27614581
TI - Home infusion of intravenous velaglucerase alfa: Experience from pooled clinical
studies in 104 patients with type 1 Gaucher disease.
AB - The introduction of a home therapy option during clinical trials of velaglucerase
alfa in patients with type 1 Gaucher disease marked the first time that home
infusions have been permitted during a clinical trial for an investigational drug
for Gaucher disease. Home infusions were an available option in 4 open-label
velaglucerase alfa clinical studies to eligible patients who received their
initial infusions at a clinic. Patients who participated in the home therapy
option and received at least 10% of their infusions at home (n=100) received a
range of 11.6%-100% of their scheduled infusions at home (median 87.5%),
excluding infusions received at the clinic during protocol-mandated visits. The
length of time over which individual patients received home therapy ranged from
13days to 4.56years (median 0.57years). During the time that home therapy was
available, 2904 of 3572 (81.3%) infusions were administered at home. Ten patients
experienced 62 infusion-related adverse events (IRAEs) during 38 home infusions,
with malaise, pain, hypertension, fatigue, and headache being reported most
frequently. No notable differences were found between the type and severity of
IRAEs experienced at home and those experienced at the clinic. Home infusions
administered by trained and qualified medical personnel were successfully
introduced into the velaglucerase alfa clinical development program, and fewer
than 10% of patients experienced IRAEs in the home setting. Local labeling and
practice guidelines should be consulted for administration of velaglucerase alfa
infusions at home.
PMID- 27614582
TI - Aerosol assisted self-assembly as a route to synthesize solid and hollow
spherical lignin colloids and its utilization in layer by layer deposition.
AB - Lignin, a major constituent of plant cell-wall and by-product of paper based
industries is traditionally used for low value applications (heat or electricity
generation), but its potential in high value utilization has also been widely
reported. In this work, we synthesized lignin colloidal particles using
ultrasonic spray-freezing route without any chemical functionalization of
material, and stabilized it by electrostatic route. As per our knowledge, this
technique is the first reported method which yields hollow/solid lignin colloids
having good particle size control without any chemical functionalization of
material. Dioxane soluble fraction of Alkali lignin (d-lignin) was used without
any further chemical functionalization. d-lignin dissolved in DMSO was sprayed
upon liquid nitrogen cooled copper plate using an ultrasonic nebulizer. The
resulting frozen droplets were collected and found to possess hollow and solid
morphology. Particles thus obtained were characterized for their size
distribution and morphology, and compared to theoretically anticipated values.
Size tunability of particles in relation to concentration of sprayed lignin
solution was also studied. In addition to that, six layers of lignin colloids
were deposited on quartz slide with the aid of negligible UV absorbing
polyelectrolyte aqueous solution PDADMAC [Poly (diallyldimethylammonium
chloride)]. Gradation in UV absorbing ability of lignin with increase in number
of layers could be clearly observed. Hollow and solid lignin colloids, apart from
their application in sunscreen cosmetics owing to their UV absorbing ability,
show potential applications in drug delivery also.
PMID- 27614584
TI - Arm elevation during computed tomography does not significantly alter abdominal
aortic aneurysm anatomy.
PMID- 27614583
TI - Formation and distribution of ZnO nanoparticles and its effect on E. coli in the
presence of sepiolite and silica within the chitosan matrix via sonochemistry.
AB - In this study, a new bio-nanocomposite was prepared and characterized with a
focus on the formation of hexagonal ZnO and orthorhombic zinc silicate
(Zn2SiO3(OH)2) phases under ultrasonic irradiation. Chitosan/sepiolite/ZnO and
chitosan/silica/ZnO bio-nanocomposites were synthesized using a simple solution
method in which extreme physical and chemical conditions created by cavitation
within the chitosan solution allowed for the transformation of aqueous Zn(OH)2 to
crystallized ZnO and Zn2SiO3(OH)2 in room temperature. Both the loading of
sepiolite and silica with the zinc precursor significantly influenced the
morphology and crystalline structure of the product, however, different zinc
compounds were observed. Sepiolite was exfoliated, resulting in a fine, even
colloidal solution through ultrasonic dispersion. Exfoliation of sepiolite
nanofibers led to the homogeneous dispersion of Zinc in the form of Zn(OH)2 in
chitosan matrix. When the same procedure was conducted using the silica
component, a formation of ZnO and Zn2SiO3(OH)2 was observed, components that were
not observed when the procedure was conducted using sepiolite. The average
crystalline size of ZnO was calculated as 36nm for ZnO. In addition, the
quantities of crystalline and the ZnO phase volume was determined as 15%. Through
zone of inhibition, the silica nanocomposite was discovered to have antibacterial
activity. In contrast, the sepiolite compound did not exhibit these properties.
We thus hypothesize that HO radicals, formed during ultrasonic irradiation
trigger the formation of a silicate ion (SiO32-) and formation of ZnO and
Zn2SiO3(OH)2 species in chitosan/silica/ZnO bio-nanocomposite, which causes to
exhibit these antibacterial properties against Gram-negative E. coli. Chemical
characterization and dispersion of the structure of the ZnO and Zn2SiO3(OH)2
phases were done using X-ray diffraction (XRD) and scanning electron microscopy
techniques (SEM) with EDAX and X-ray photoelectron spectroscopy (XPS).
PMID- 27614585
TI - The many faces of pancreatic serous cystadenoma: Radiologic and pathologic
correlation.
AB - Pancreatic serous cystadenoma can be categorized into microcystic, honeycomb,
oligocystic, and solid patterns based on imaging appearance. The presence of
typical computed tomography (CT) features helps to differentiate serous
cystadenomas from other cystic and solid pancreatic masses. Cases with atypical
features present a diagnostic challenge as they can mimic malignant neoplasms.
This article reviews pathophysiology, prevalence, CT features, mimickers and
recommendations for management of pancreatic serous cystadenoma.
PMID- 27614586
TI - Psammomys obesus, a unique model of metabolic syndrome, inflammation and
autophagy in the pathologic development of hepatic steatosis.
AB - The aim of our transmission electron microscope study was to show, for the first
time, the alteration of liver cells involved in the evolution of steatosis to
steatohepatitis on a murine model of the diet-induced metabolic syndrome,
Psammomys obesus. This pathologic evolution was induced by using the standard
laboratory diet during 10 months, and analyzed with metabolic studies and the
immunohistochemistry technique. Four months later, hepatocytes charged with lipid
vacuoles were involved in autophagy. Furthermore, in the sinusoids, we observed
Kupffer cells, neutrophils and macrophages. All those cells were associated with
necrotic hepatocytes inducing hepatocellular necrosis. We also noticed a
synthesis of extracellular matrix in excess, caused by proliferation and
activation of hepatic stellate cells in necrotic areas. We observed as well a
fragmentation of the endoplasmic reticulum, which formed isolated membranes
(phagophores) surrounding mitochondria. The complex membrane-mitochondria formed
like an autophagosome. Thus, a defect in autophagy favored the development and
progression of steatohepatitis. In conclusion, our results suggest that P. obesus
is very well adapted for experimental research, and could help improve the early
therapeutic management of patients and the prevention of autophagic risks in the
liver.
PMID- 27614587
TI - The Effect of Peer Review on the Quality of Data Graphs in Annals of Emergency
Medicine.
AB - STUDY OBJECTIVE: We determine how peer review affects the quality of published
data graphs and how the appointment of a graphics editor affects the quality of
graphs in an academic medical journal. METHODS: We conducted an observational
time-series analysis to quantify the qualities of data graphs in original
manuscripts and published research articles in Annals of Emergency Medicine from
2006 to 2012. We retrospectively analyzed 3 distinct periods: before the use of a
graphics editor, graph review after a manuscript's acceptance, and graph review
just before the first request for revision. Raters blinded to study year scored
the quality of original and published graphs using an 85-item instrument.
Editorial comments about graphs were classified into 4 major and 16 minor
categories. RESULTS: We studied 60 published articles and their corresponding
original submissions during each period (2006, 2009, and 2012). The number of
graphs increased 31%, their median data density increased 50%, and quality
(completeness [+42%], visual clarity [+64%], and special features [+66%])
increased from submission to publication in all 3 periods. Although geometric
mean (0.69, 0.86, and 1.2 pieces of information/cm2) and median data density
(0.44, 0.70, and 1.2 pieces of information/cm2) were higher in the graphics
editor phases, mean data density, completeness, visual clarity, and other markers
of quality did not improve or decreased with dedicated graphics editing. The
majority of published graphs were bar or pie graphs (49%, 53%, and 60% in 2006,
2009, and 2012, respectively) with low data density in all 3 years. CONCLUSION:
Peer review unquestionably improved graph quality. However, data densities of
most graphs barely exceeded that of printed text, and many graphs failed to
present the majority of available data and did not convey those data clearly;
there remains much room for improvement. The timing of graphics editor
involvement appears to affect the effect of the graph review process.
PMID- 27614588
TI - Fabrication of FDTS-modified PDMS-ZnO nanocomposite hydrophobic coating with anti
fouling capability for corrosion protection of Q235 steel.
AB - Perfluorodecyltrichlorosilane-based poly(dimethylsiloxane)-ZnO (FDTS-based PDMS
ZnO) nanocomposite coating with anti-corrosion and anti-fouling capabilities has
been prepared using a one-step fabrication technique. XPS analysis and contact
angle measurements showed the fluorine content to increase, while the
hydrophobicity of the coatings decreased with addition of FDTS. XRD analysis
revealed existence of ZnO nanoparticles of dimensions ranging from 11.45 to
93.01nm on the surface of coatings, with the mean particle size decreasing with
FDTS addition, and was confirmed by SEM and TEM observations. Interestingly, the
anti-corrosion performance and mechanical properties of the coatings increased
remarkably on addition of FDTS. Indeed, the observed low adhesion strength,
surface energies and the outstanding anti-corrosive properties imply that the
obtained coating would be useful in anti-fouling applications.
PMID- 27614590
TI - Unilateral absence of the right pulmonary artery with associated aortopulmonary
collaterals and bullous lung lesions in a dog.
AB - This case report describes a combination of congenital cardiopulmonary
abnormalities found in a 1-year-old Labrador Retriever. To the authors' knowledge
this combination of cardiopulmonary abnormalities has not been previously
reported in veterinary medicine. Unilateral absence of the right pulmonary artery
associated with unilateral right-sided aortopulmonary collaterals was observed.
These aortopulmonary collaterals preserved the blood supply to the right lung
lobes but led to left ventricular volume overload. There was also evidence of
severe bullous lung disease in the right lung, which was suspected to be
secondary to pulmonary sequestration as a result of the anomalous hemi-pulmonary
circulation. The diagnosis of left-sided volume overload was achieved by
radiography and echocardiography while the remainder of the findings was
diagnosed on computed tomography angiography. The owner refused surgery for
occlusion of the shunting vessels and therapy at standard doses of benazepril,
spironolactone and pimobendan was initiated. In spite of the severe volume
overload, the dog remained stable with static non-progressive clinical signs and
stable echocardiographic findings at 1-year follow-up. The case report also acts
as a reminder of the possible occurrence of unusual extra-cardiac shunts in the
presence of an unexplained left ventricular volume overload.
PMID- 27614589
TI - Cytoreductive surgery for head and neck squamous cell carcinoma in the new age of
immunotherapy.
AB - Cytoreductive surgery is an approach to cancer treatment that aims to reduce the
number of cancer cells via resection of primary tumor or metastatic deposits, in
an effort to minimize a potentially immunosuppressive tumor burden, palliate
symptoms, and prevent complications. Furthermore, it provides a platform for
investigation of biomarkers with the goal of optimizing immunotherapy to reverse
the immunosuppressive tumor microenvironment and enhance adaptive immune
responses. Ultimately, our group aims to exploit the concept that successful
cancer therapy is dependent upon an effective immune response. Surgery will
remain an integral part of head and neck squamous cell carcinoma (HNSCC)
treatment in the future, even as checkpoint inhibitors, co-stimulatory molecules,
vaccines, adoptive T cell therapy and other novel agents enter clinical routine.
Cytoreductive resection may provide an effective platform for immunotherapy and
biomarker directed interventions to improve outcomes for patients with HNSCC.
PMID- 27614592
TI - Measurable Outcomes After Transfer From Pediatric to Adult Providers in Youth
With Chronic Illness.
AB - Children with chronic medical conditions are requiring transition services to
prepare for transfer of care. There has been little data on what qualifies as a
successful transition or how to measure this goal. The purpose of this review was
to identify measurable patient-level outcomes for transitioning youth with
chronic illness from pediatric to adult health care. An integrative literature
search was conducted using CINAHL and OVID Medline. Key words included transition
to adult care and health transition. Research articles published between 2002 and
2015 and reported on measurable patient-level outcomes in youth with chronic
illnesses were included. The initial search yielded 556 articles and 19 articles
were selected. Most of the research reporting on outcomes after transfer is
nonexperimental using secondary data. Additionally, there is inconsistency in the
use of term transition. In the specific outcomes identified, there is little
uniformity in measurement both in terms of timing and standardization of
measurement. Further research is needed on outcomes after transfer that includes
standardized measures and time intervals in order to evaluate successful
transition services. This research is essential for health care providers who are
instrumental in supporting young people during this high risk period.
PMID- 27614591
TI - Safety of Concurrent Boston Type I Keratoprosthesis and Glaucoma Drainage Device
Implantation.
AB - PURPOSE: To evaluate the safety of concurrent Boston type I keratoprosthesis
(KPro) and glaucoma drainage device (GDD) implantation. DESIGN: Retrospective
comparative study of a consecutive cohort of patients. SUBJECTS: Patients who
underwent KPro implantation by a single surgeon (A.J.A.) with or without 1
concurrent Ahmed GDD (New World Medical, Inc., Rancho Cucamonga, CA) implantation
between January 1, 2005, and January 31, 2015, were included. Patients with fewer
than 3 months of follow-up or a history of previous KPro implantation were
excluded. METHODS: Preoperative, operative, and postoperative data were collected
for each procedure. All comparisons were made between KPro procedures performed
with or without concurrent GDD implantation. The Fisher exact test (2-tailed) was
used to compare proportions, Student t test and Wilcoxon rank-sum test were used
to compare means, and the log-rank test was used to compare time-to-outcome
events. MAIN OUTCOME MEASURES: The primary outcome was frequency of the composite
variable, that is, any serious vision-threatening postoperative complication,
which included sterile vitreitis, endophthalmitis, hypotony maculopathy,
suprachoroidal hemorrhage, retinal detachment, stromal necrosis, and infectious
keratitis. Secondary outcomes included intraocular pressure control, worsening of
visual acuity, cystoid macular edema, retroprosthetic membrane formation,
persistent epithelial defect formation, GDD exposure, and KPro removal. RESULTS:
One hundred thirty-seven KPro procedures were performed in 129 patients: 91
(66.4%) KPro alone and 46 (33.6%) KPro plus GDD. There were no statistically
significant differences between the 2 groups in terms of the incidence of vision
threatening postoperative complications. None of the 46 GDDs placed at the same
time as the KPro became exposed during an average follow-up of 44 months.
CONCLUSIONS: Compared with KPro alone, GDD placement combined with KPro was not
associated with increased postoperative complications.
PMID- 27614594
TI - Transabdominal cervicoisthmic cerclage.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614593
TI - Is there anything wrong with undergraduate medical education in Saudi Arabia.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614595
TI - Evaluation of mail survey for the assessment of tobacco use among adults.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614596
TI - Is stepwise application of ventouse necessary?
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614597
TI - Influenza viruses in children attending major referral center in Saudi Arabia.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614598
TI - Contact dermatitis in auto repair workers.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614599
TI - The pattern of brachial plexus lesions.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614602
TI - The role of fine needle aspiration biopsy and frozen section in the management of
nodular thyroid lesions.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614601
TI - Removable partial prosthodontic techniques in practice.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614600
TI - Psychiatric screening among Type II diabetic patients: Validity of the General
Health Questionnaire-12.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614603
TI - Ruptured tubal pregnancy co-existing with acute appendicitis. A rare occurrence.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614604
TI - Dilatation of fusiform to sacular form right coronary arter aneurysm.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614605
TI - Peak expiratory flow rate nomogram in Libyan boys and girls in Tripoli.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614606
TI - Knowledge assessment about AIDS among primary health care centers female
attendees and health care providers in Abha - Kingdom of Saudi Arabia.
AB - Full text is available as a scanned copy of the original print version.
PMID- 27614607
TI - Transforming growth factor (TGF) beta1 and Smad signalling pathways: A likely key
to EMT-associated COPD pathogenesis.
AB - BACKGROUND AND OBJECTIVE: COPD is characterized by poorly reversible airflow
obstruction usually due to cigarette smoking. Transforming growth factor (TGF)
beta1 has been implicated in the pathogenesis of COPD, and in particular a
process called epithelial mesenchymal transition (EMT), which may well be an
intermediatory between smoking and both airway fibrosis and lung cancer. The
downstream classical or 'canonical' TGF-beta1 pathway is via the phosphorylated
(p) Smad transcription factor system. METHODS: We have investigated TGF-beta1
expression and its 'pSmad fingerprint' in bronchoscopic airway biopsies from
patients with COPD, and in smoking and non-smoking controls. A cross-sectional
immunohistochemical study compared TGF-beta1 and pSmad 2, 3 (excitatory) and 7
(inhibitory) expression in cells and blood vessels of three compartments of large
airways: epithelium (especially the basal region), reticular basement membrane
(Rbm) and underlying lamina propria (LP). RESULTS: TGF-beta1 expression was
generally higher in COPD subjects throughout the airway wall (P < 0.01), while
pSmad 2/3 expression was associated with smoking especially in current smoking
COPD (P < 0.05). Expression of inhibitory pSmad 7 was also prominently reduced in
patients with COPD in contrast to smokers and controls (P < 0.01). In addition,
pSmad, but not TGF-beta1 expression, was related to airflow obstruction and a
canonical EMT biomarker (S100 A4) expression. CONCLUSION: Activation of the Smad
pathway in the airways is linked to EMT activity and loss of lung function. The
disconnection between TGF-beta1 and pSmad in terms of relationships to EMT
activity and lung function suggests that factors other than or in addition to TGF
beta1 are driving the process.
PMID- 27614608
TI - Response to 'Mono-ovulation in women with polycystic ovary syndrome: the role of
step-up, ultra-low-dose gonadotrophin regimen'.
PMID- 27614609
TI - Safety of Outpatient vs Inpatient Percutaneous Radiological Gastrostomy Tubes in
Patients with Head and Neck Cancers.
PMID- 27614610
TI - How Well Are We Respecting Patient Privacy in Medical Imaging? Lessons Learnt
From a Departmental Audit.
AB - RATIONALE AND OBJECTIVES: Preservation of patient privacy and dignity are basic
requirements for all patients visiting a hospital. The purpose of this study was
to perform an audit of patients' satisfaction with privacy whilst in the
Department of Medical Imaging (MI) at the Civic Campus of the Ottawa Hospital.
MATERIALS AND METHODS: Outpatients who underwent magnetic resonance imaging
(MRI), computed tomography (CT), ultrasonography (US), and plain film (XR)
examinations were provided with a survey on patient privacy. The survey asked
participants to rank (on a 6-point scale ranging from 6 = excellent to 1 = no
privacy) whether their privacy was respected in 5 key locations within the
Department of MI. The survey was conducted over a consecutive 5-day period.
RESULTS: A total of 502 surveys were completed. The survey response rate for each
imaging modality was: 55% MRI, 42% CT, 45% US, and 47% XR. For each imaging
modality, the total percentage of privacy scores greater than or equal to 5 were:
98% MRI, 96% CT, 94% US, and 92% XR. Privacy ratings for the MRI reception and
waiting room areas were significantly higher in comparison to the other imaging
modalities (P = .0025 and P = .0227, respectively). CONCLUSION: Overall, patient
privacy was well respected within the Department of MI.
PMID- 27614612
TI - Dealing with time-varying recruitment and length in Hill-type muscle models.
AB - Hill-type muscle models are often used in muscle simulation studies and also in
the design and virtual prototyping of functional electrical stimulation systems.
These models have to behave in a sufficiently realistic manner when recruitment
level and contractile element (CE) length change continuously. For this reason,
most previous models have used instantaneous CE length in the muscle's force vs.
length (F-L) relationship, but thereby neglect the instability problem on the
descending limb (i.e. region of negative slope) of the F-L relationship. Ideally
CE length at initial recruitment should be used but this requires a multiple
motor-unit muscle model to properly account for different motor-units having
different initial lengths when recruited. None of the multiple-motor-unit models
reported in the literature have used initial CE length in the muscle's F-L
relationship, thereby also neglecting the descending limb instability problem. To
address the problem of muscle modelling for continuously varying recruitment and
length, and hence different values of initial CE length for different motor
units, a new multiple-motor-unit muscle model is presented which considers the
muscle to comprise 1000 individual Hill-type virtual motor-units, which determine
the total isometric force. Other parts of the model (F-V relationship and passive
elements) are not dependent on the initial CE length and, therefore, they are
implemented for the muscle as a whole rather than for the individual motor-units.
The results demonstrate the potential errors introduced by using a single-motor
unit model and also the instantaneous CE length in the F-L relationship, both of
which are common in FES control studies.
PMID- 27614611
TI - Genital tract lesions in sexually mature Gottingen minipigs during the initial
stages of experimental vaginal infection with Chlamydia trachomatis serovar D.
AB - BACKGROUND: Chlamydia is one of the most common sexually transmitted diseases in
humans worldwide, causing chronic lesions in the reproductive tract. Due to its
often asymptomatic course, there is limited knowledge about the initial changes
in the genital tract following infection. This study employs a novel sexually
mature minipig model to investigate the initial histopathological changes
following vaginal infection with Chlamydia trachomatis serovar D. RESULTS: A
vaginal inoculation resulted in an infection primarily affecting the lower
genital tract. The histopathological changes were characterized by a
subepithelial inflammation consisting of neutrophils and mononuclear cells,
followed by an increase in the number of plasma cells within the sub-epithelial
stroma of the vagina. Detection of Chlamydia was associated with expression of
cyclooxygenase-2 and interleukin-8 by superficial epithelial cells. The infection
was self-limiting, with a duration of 7 days. CONCLUSION: Neutrophils, plasma
cells and IL-8 have been linked with Chlamydia genital infection of unknown
duration in human patients. In this study, we observe a similar pattern of local
immune response/inflammation following experimental inoculation suggesting this
porcine model shows promise as a model for translational chlamydia research.
PMID- 27614613
TI - The role of anisotropic expansion for pulmonary acinar aerosol deposition.
AB - Lung deformations at the local pulmonary acinar scale are intrinsically
anisotropic. Despite progress in imaging modalities, the true heterogeneous
nature of acinar expansion during breathing remains controversial, where our
understanding of inhaled aerosol deposition still widely emanates from studies
under self-similar, isotropic wall motions. Building on recent 3D models of multi
generation acinar networks, we explore in numerical simulations how different
hypothesized scenarios of anisotropic expansion influence deposition outcomes of
inhaled aerosols in the acinar depths. While the broader range of particles
acknowledged to reach the acinar region (dp=0.005-5.0MUm) are largely unaffected
by the details of anisotropic expansion under tidal breathing, our results
suggest nevertheless that anisotropy modulates the deposition sites and fractions
for a narrow band of sub-micron particles (dp~0.5-0.75MUm), where the fate of
aerosols is greatly intertwined with local convective flows. Our findings
underscore how intrinsic aerosol motion (i.e. diffusion, sedimentation)
undermines the role of anisotropic wall expansion that is often attributed in
determining aerosol mixing and acinar deposition.
PMID- 27614615
TI - Lightness, chroma and hue differences on visual shade matching.
AB - OBJECTIVES: To analyze the influence of lightness, chroma and hue differences on
visual shade matching performed by dental students. METHODS: 100 dental students
(DS) volunteers with normal vision participated in the study. A spectroradiometer
(SP) was used to measure the spectral reflectance of 4 extracted human upper
central incisors (UCI 1-4) and shade tabs from Vita Classical (VC) and Vita
Toothguide 3D-Master (3D) shade guides. Measurements were performed over a gray
background, inside a viewing booth and under D65 illuminant (diffuse/0 degrees
geometry). Color parameters (L*, a*, b*, C* and h degrees ) were calculated. DS
used VC and 3D to visually select the best shade match for each UCI. CIE metric
differences (Deltaa*,Deltab*,DeltaL', DeltaC' and DeltaH') and CIEDE2000(2:1:1)
lightness (DeltaEL), chroma (DeltaEC) and hue (DeltaEH) differences were obtained
from each UCI and the first three shades selected by DS and the first option
using CIELAB, CIEDE2000(1:1:1) and CIEDE2000(2:1:1) color difference metrics. The
closest CIELAB color-discrimination ellipsoid (from RIT-DuPont visual color
difference data) to each UCI was selected for the analysis of visual shade
matching. RESULTS: DS showed a preference for shades with lower chroma (DeltaC'
and DeltaEC) and/or hue (DeltaH' and DeltaEH) values instead of shades with lower
lightness values (DeltaL' and DeltaEL). Most best visual matches were near the
tolerance ellipsoid centered on tooth shade. SIGNIFICANCE: This study is an
attempt to partially explain the inconsistencies between visual and instrumental
shade matching and the limitations of shade guides. Visual shade matching was
driven by color differences with lower chroma and hue values.
PMID- 27614614
TI - Characteristics and adaptive strategies linked with falls in stroke survivors
from analysis of laboratory-induced falls.
AB - Falls are the most common and expensive medical complication in stroke survivors.
There is remarkably little information about what factors lead to a fall in
stroke survivors. With few exceptions, the falls literature in stroke has focused
on relating metrics of static balance and impairment to fall outcomes in the
acute care setting or in community. While informative, these studies provide
little information about what specific impairments in a stroke-survivor's
response to dynamic balance challenges lead to a fall. We identified the key
kinematic characteristics of stroke survivors' stepping responses following a
balance disturbance that are associated with a fall following dynamic balance
challenges. Stroke survivors were exposed to posteriorly-directed translations of
a treadmill belt that elicited a stepping response. Kinematics were compared
between successful and failed recovery attempts (i.e. a fall). We found that the
ability to arrest and reverse trunk flexion and the ability to perform an
appropriate initial compensatory step were the most critical response
contributors to a successful recovery. We also identified 2 compensatory
strategies utilized by stroke survivors to avoid a fall. Despite significant post
stroke functional impairments, the biomechanical causes of trip-related falls by
stroke survivors appear to be similar to those of unimpaired older adults and
lower extremity amputees. However, compensatory strategies (pivot, hopping) were
observed.
PMID- 27614616
TI - Laparoscopy-Assisted Trans-Gastric Rendez-vous for the Treatment of Common Bile
Duct Stones in Patients with Prior Roux-en-Y Gastric Bypass.
AB - BACKGROUND: Common bile duct (CBD) stones in a Roux-en-Y gastric bypass (RYGB)
represent a major challenge for ERCP due to long-limb anatomy. Trans-gastric
approach has been proposed but entails high ERCP-related risks. Laparoscopy
assisted trans-gastric rendez-vous (LATG-RV) is a one-step procedure that may
lower the risks of these patients. METHODS: We describe our initial experience in
four patients with past history of RYGB and CBD stones. RESULTS: All patients
underwent LATG-RV and had successful CBD stone clearance. Postoperative course
was uneventful with normal amylase levels. Average procedure time was 105 min and
postoperative stay 2 days. CONCLUSION: LATG-RV is a safe and effective procedure
for the clearance of CBD stones in RYGB patients. It may have fewer complications
and shorter operative time than regular trans-gastric ERCP.
PMID- 27614617
TI - Biological function of unique sulfated glycosaminoglycans in primitive chordates.
AB - Glycosaminoglycans with unique sulfation patterns have been identified in
different species of ascidians (sea squirts), a group of marine invertebrates of
the Phylum Chordata, sub-phylum Tunicata (or Urochordata). Oversulfated dermatan
sulfate composed of [4-alpha-L-IdoA-(2-O-SO3)-1 -> 3-beta-D-GalNAc(4-OSO3)-1]n
repeating disaccharide units is found in the extracellular matrix of several
organs, where it seems to interact with collagen fibers. This dermatan sulfate co
localizes with a decorin-like protein, as indicated by immunohistochemical
analysis. Low sulfated heparin/heparan sulfate-like glycans composed mainly of [4
alpha-L-IdoA-(2-OSO3)-1 -> 4-alpha-D-GlcN(SO3)-1 (6-O-SO3)-1]n and [4-alpha-L
IdoA-(2-O-SO3)-1 -> 4-alpha-D-GlcN(SO3)-1]n have also been described in
ascidians. These heparin-like glycans occur in intracellular granules of oocyte
assessory cells, named test cells, in circulating basophil-like cells in the
hemolymph, and at the basement membrane of different ascidian organs. In this
review, we present an overview of the structure, distribution, extracellular and
intracellular localization of the sulfated glycosaminoglycans in different
species and tissues of ascidians. Considering the phylogenetic position of the
subphylum Tunicata in the phylum Chordata, a careful analysis of these data can
reveal important information about how these glycans evolved from invertebrate to
vertebrate animals.
PMID- 27614619
TI - Influence of patient personality in the treatment of rheumatoid arthritis.
AB - Individualized treatment of rheumatoid arthritis (RA) based on genetic/serologic
factors is increasingly accepted. Moreover, patients are more actively involved
in the management of their disease. However, personality has received little
attention with respect to perception of the need and adherence to treatment. Our
objective was to evaluate whether patient personality was associated with the
acceptance or rejection of more aggressive early treatment. We performed a cross
sectional study in two hospitals with early arthritis clinics where
sociodemographic, clinical, and therapeutic variables are systematically
recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional
Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related
Control Scale. Aggressive treatment was considered if patients received more than
two DMARDs or biological agents during the first year of follow-up. Multivariate
logistic regression analysis was performed to determine predictors of aggressive
treatment. One hundred seventy-six RA patients were included (80 % women, disease
begin median age 55 years). Treatment was considered aggressive in 57.9 % of the
sample. Scores were high in extraversion in 50.8 % of patients, neuroticism in
29.5 % and psychoticism in 14.7 %. Neuroticism was the only factor associated
with aggressive treatment, which was less probable (p = 0.04, OR = 0.40).
Neuroticism also decreased the possibility of receiving a combination of
biologics and DMARDs (p = 0.04, OR = 0.28). Patients with high scores on
neuroticism are more worried, obsessive and hypochondriac, leading them to reject
more aggressive therapy. It is important to educate about their disease so that
they will accept more aggressive approaches in clear cases of poor outcome.
PMID- 27614620
TI - Feasibility of attached cultivation for polysaccharides production by
Porphyridium cruentum.
AB - Porphyridium cruentum is one of the most valued microalgae species able to
produce both pigments and exopolysaccharides. Conventional liquid suspended
cultivation in ponds and photobioreactors show its disadvantages in lower
cultivation efficiency and higher stirring power consumption due to the high
viscosity of the medium by the accumulation of polysaccharides. In this work, a
new method of culture (called attached cultivation) based on the growth of
microalgae using a supporting surface was successfully applied to the cultivation
of P. cruentum and the effect of the main influential parameters on its growth
rate and polysaccharides production has been investigated. Higher values of these
factors resulted in a faster growth rate and, in particular, optimum values of
6.98 g m-2 for initial biomass density, 100 umol m-2 s-1 for light intensity,
continuous illumination, 2.0 % for CO2 concentration, and 0.1 v v-1 min-1 for
aeration rate produced the best polysaccharide production of 42 % dry weight. The
nutrition profile of P. cruentum obtained in attached and suspended cultivations
was similar. Overall these results demonstrate that the attached cultivation is a
promising technique which greatly improves the growth rate of P. cruentum as well
as its production of polysaccharides and, therefore, it is worth enhancing to be
exploited for commercial application.
PMID- 27614618
TI - Dimethyl Fumarate and Monomethyl Fumarate Promote Post-Ischemic Recovery in Mice.
AB - Oxidative stress plays an important role in cerebral ischemia-reperfusion injury.
Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are
antioxidant agents that can activate the nuclear factor erythroid-2-related
factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of
antioxidant proteins. Here, we evaluated the impact of DMF and MMF on ischemia
induced brain injury and whether the Nrf2 pathway mediates the effects provided
by DMF and MMF in cerebral ischemia-reperfusion injury. Using a mouse model of
transient focal brain ischemia, we show that DMF and MMF significantly reduce
neurological deficits, infarct volume, brain edema, and cell death. Further, DMF
and MMF suppress glial activation following brain ischemia. Importantly, the
protection of DMF and MMF was mostly evident during the subacute stage and was
abolished in Nrf2-/- mice, indicating that the Nrf2 pathway is required for the
beneficial effects of DMF and MMF. Together, our data indicate that DMF and MMF
have therapeutic potential in cerebral ischemia-reperfusion injury and their
protective role is likely mediated by the Nrf2 pathway.
PMID- 27614623
TI - Cerebellar Adrenomedullinergic System. Role in Cardiovascular Regulation.
AB - Adrenomedullin (AM) is a multifunctional peptide which exerts numerous biological
activities through the activation of AM1 (CRLR + RAMP2) and AM2 (CRLR + RAMP3)
receptors. AM immunoreactivity, AM binding sites and CRLR, RAMP1, RAMP2 and RAMP3
are expressed in rat cerebellar vermis. AM binding sites are discretely and
differentially distributed in the rat cerebellar cortex with higher levels
detected in SHR when compared with WKY rats. In addition, there is an up
regulation of cerebellar CGRP1 (CRLR + RAMP1) and AM2 (CRLR + RAMP3) receptors
and a down-regulation of AM1 (CRLR + RAMP2) receptor during hypertension
associated with a decreased AM expression. These changes may constitute a
mechanism which contributes to the development of hypertension, and supports the
notion that cerebellar AM is involved in the regulation of blood pressure.
Cerebellar AM activates ERK, increases cAMP, cGMP and nitric oxide, and decreases
antioxidant enzyme activity. These effects are mediated through AM1 receptor
since they are blunted by AM(22-52). AM-stimulated cAMP production is mediated
through AM2 and CGRP receptors. In vivo administration of AM into the cerebellar
vermis caused a profound, specific and dose-dependent hypotensive effect in SHR,
but not in normotensive WKY rats. This effect was mediated through AM1 receptor
since it was abolished by AM(22-52). In addition, AM injected into the cerebellar
vermis reduced vasopressor response to footshock stress. These findings
demonstrate dysregulation of cerebellar AM system during hypertension, and
suggest that cerebellar AM plays an important role in the regulation of blood
pressure. Likewise, they constitute a novel mechanism of blood pressure control
which has not been described so far.
PMID- 27614621
TI - A phase III multicenter, randomized, controlled study of combined androgen
blockade with versus without zoledronic acid in prostate cancer patients with
metastatic bone disease: results of the ZAPCA trial.
AB - OBJECTIVE: To examine the antitumor activity of zoledronic acid (ZA) combined
with androgen deprivation therapy (ADT) for men with treatment-naive prostate
cancer and bone metastasis. METHODS: We enrolled 227 men with treatment-naive
prostate cancer and bone metastasis. Participants were randomly assigned (1:1
ratio) to receive combined androgen blockade alone (CAB group) or ZA with
combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to
the first skeletal-related event (TTfSRE), and overall survival (OS) rates were
estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated
using the Cox proportional hazards model. Median follow-up duration was 41.5
months. RESULTS: Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups,
respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline
prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8
months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p =
0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups,
respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the
groups. CONCLUSIONS: This study failed to demonstrate that combined use of ZA and
ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and
bone metastasis. However, it generates a new hypothesis that the combined therapy
could delay the development of castration resistance in a subgroup of patients
with low baseline prostate-specific antigen values <200 ng/mL. The treatment also
significantly prolonged TTfSRE but did not affect OS.
PMID- 27614622
TI - The neutrophil-to-lymphocyte ratio as a predictor of intravesical recurrence in
patients with upper urinary tract urothelial carcinoma treated with radical
nephroureterectomy.
AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic
inflammation associated with recurrence and poor prognosis in numerous cancer
types. The aim of this study was to evaluate the use of the NLR as a biomarker
for intravesical recurrence (IVR) in patients undergoing radical
nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) for
the first time. METHODS: We retrospectively analyzed the records of 100 patients
with UTUC who had undergone RNU between 1999 and 2015 at our institution. The
association between the preoperative NLR and IVR were assessed using multivariate
models. RESULTS: Among the 100 patients enrolled in the study, 33 developed IVR
during a median follow-up of 34 months. The receiver operating characteristic
analysis revealed that the optimum cut-off value for the preoperative NLR was
>3.8. A high preoperative NLR (n = 21) was associated with a significantly
increased risk of lymph node involvement (p = 0.036) and IVR (p = 0.034) compared
with a low preoperative NLR (n = 79). IVR-free survival in patients with a high
preoperative NLR was significantly worse than that of patients with a low
preoperative NLR (p = 0.018). On multivariate analysis, the preoperative NLR
[hazard ratio (HR) 2.49; p = 0.015] and tumor multifocality (HR 2.96; p = 0.024)
were independent risk factors predictive of IVR. CONCLUSION: In our study
population of patients with UTUC who had undergone RNU the preoperative NLR was
associated with a significantly increased risk of IVR, suggesting that the NRL
could be a useful biomarker for predicting IVR.
PMID- 27614624
TI - Concha Bullosa in Paleoanthropological Material.
AB - Concha bullosa is a variant of the sinonasal anatomy in which the middle nasal
turbinate contains pneumatized cells, which leads to turbinate enlargement. The
reason for concha bullosa formation is unclear, but the variant is seen in up to
half the modern population and it may predispose to paranasal sinusitis. The
variant has hitherto featured little in paleopathology. Therefore, in the present
study we seek to determine the presence of concha bullosa, with the coexisting
hypertrophy of the middle turbinate and signs of sinusitis or other pathology of
the paranasal complex, in a population living in Tomersdorf-Toporow in the Upper
Lausatia, a historical region in Germany and Poland, presently Zgorzelec County
in the Lower Silesian voivodeship, at the turn of the nineteenth and twentieth
century. The material consisted of 32 skeletons (24 males, 8 females). The
gender, age, and stress indicators and the presence of pathological signs were
assessed, followed by CT of the skulls. We found 2 skulls (6.3 %) with concha
bullosa. In one case septal nasal deviation was present. We conclude that the
incidence of concha bullosa could be lower in the past times than at present.
Wider research is necessary to settle whether concha bullosa is indeed a rare
respiratory paleopathology or a missed, and thus underreported observation.
PMID- 27614625
TI - A Practical System for High-Throughput Screening of Mutants of Bacillus
fastidiosus Uricase.
AB - For high-throughput screening (HTS) of Bacillus fastidiosus uricase mutants, a
practical system was proposed. By error-prone PCR with final 1.5 mM MnCl2, two
focused libraries of mutants for A1-V158 and V150-D212 were generated separately.
After induced expression of individual clones in 48-well microplates, Escherichia
coli cells (BL21) were lyzed by 1.0 M Tris-HCl at pH 9.0 in 96-well microplates
at 25 degrees C for 7.5 ~ 10.5 h; uricase reaction was continuously monitored
with 0.15 mM uric acid in 96-well plates by absorbance at 298 nm to estimate V
m/K m by kinetic analysis of reaction curve for comparison. V m/K m was resistant
to initial uric acid levels with an upper limit 3-fold over that of initial
rates. By receiver-operator-characteristic analysis of the recognition of the one
of higher activity in uricase pair whose specific activity ratio was 1.8 or 3.3,
the area-under-the-curve was comparable to that with cell lysates prepared by
sonication treatment. A cutoff for the maximum Youden index was thus developed to
recognize positive mutants of 1-fold higher activity. Indeed, mutant
L171I/Y182F/Y187F/A193S of higher activity but lower thermostability at pH 7.4
and mutant V144A of higher activity and consistent thermostability were
discovered. Therefore, the proposed system was practical for HTS of uricase
mutants.
PMID- 27614626
TI - Anthropometrically predicted visceral adipose tissue and blood-based biomarkers:
a cross-sectional analysis.
AB - PURPOSE: We hypothesized that anthropometrically predicted visceral adipose
tissue (apVAT) accounts for more variance in blood-based biomarkers of glucose
homeostasis, inflammation, and lipid metabolism than body mass index (BMI), waist
circumference (WC), and the combination of BMI and WC (BMI + WC). METHODS: This
was a cross-sectional analysis of 10,624 males and females who participated in
the Third National Health and Nutrition Examination Survey (NHANES III; 1988
1994). apVAT was predicted from a validated regression equation that included
age, height, weight, waist, and thigh circumferences. Bootstrapped linear
regression models were used to compare the proportion of variance (R 2) in
biomarkers explained by apVAT, BMI, WC, and BMI + WC. RESULTS: apVAT accounted
for more variance in biomarkers of glucose homeostasis than BMI (?R 2 = 8.4-11.8
%; P < 0.001), WC (?R 2 = 5.5-8.4 %; P < 0.001), and BMI + WC (?R 2 = 5.1-7.7 %;
P < 0.001). apVAT accounted for more variance in biomarkers of inflammation than
BMI (DeltaR 2 = 3.8 %; P < 0.001), WC (DeltaR 2 = 3.1 %; P < 0.001), and BMI + WC
(DeltaR 2 = 2.9 %; P < 0.001). apVAT accounted for more variance in biomarkers of
lipid metabolism than BMI (DeltaR 2 = 2.9-9.2 %; P < 0.001), WC (DeltaR 2 = 2.9
5.2 %; P < 0.001), and BMI + WC (DeltaR 2 = 2.4-4.1 %; P <= 0.01). CONCLUSIONS:
apVAT, estimated with simple and widely used anthropometric measures, accounts
for more variance in blood-based biomarkers than BMI, WC, and BMI + WC.
Clinicians and researchers may consider utilizing apVAT to characterize cardio
metabolic health, particularly in settings with limited availability of imaging
and laboratory data.
PMID- 27614627
TI - Immunohistochemical analysis of dentin matrix protein 1 (Dmp1) phosphorylation by
Fam20C in bone: implications for the induction of biomineralization.
AB - Dmp1 is an acidic phosphoprotein that is specifically expressed in osteocytes.
During the secretory process, the full-length, precursor Dmp1 is cleaved into N-
and C-terminal fragments. C-terminal Dmp1 is phosphorylated, becoming a highly
negatively charged domain that may assist in bone mineralization by recruiting
calcium ions and influencing subsequent mineral deposition. It has been recently
reported that the Golgi-localized protein kinase Fam20C phosphorylates Dmp1 in
vitro. To investigate this phosphorylation in situ, we determined the locations
of phosphorylated Dmp1 and Fam20C in rat bones using immunohistochemistry. During
osteocytogenesis, osteoblastic, osteoid, and young osteocytes (but not old
osteocytes) express Dmp1 mRNA and contain Dmp1 protein in the Golgi apparatus.
These Dmp1-producing cells were distributed across the surface layer of cortical
bone. Using immunofluorescence, we found that N- and C-terminal Dmp1 fragments
were predominantly distributed along the lacunar walls and canaliculi of
mineralized bone, respectively, but were not present in the osteoid matrix. We
also found that Fam20C and its substrate, C-terminal Dmp1, colocalized in the
Golgi of osteoblastic, osteoid, and young osteocytes. Furthermore, phosphorylated
C-terminal Dmp1 was present in the Golgi of young osteocytes. Double-labeling
immunoelectron microscopy revealed that phosphorylated C-terminal Dmp1 localized
to the canalicular wall in mineralized bone. These findings suggest that C
terminal Dmp1 is phosphorylated within osteocytes and then secreted into the
pericanalicular matrix of mineralized bone. Phosphorylated, negatively charged C
terminal Dmp1 in the pericanalicular matrix may play an important role in bone
mineralization by recruiting calcium ions.
PMID- 27614628
TI - DNA repair mechanisms in embryonic stem cells.
AB - Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the
pluripotency to differentiate into all cell types in the body. Therefore, as a
renewable source of various functional cells in the human body, ESCs hold great
promise for human cell therapy. During the rapid proliferation of ESCs in
culture, DNA damage, such as DNA double-stranded breaks, will occur in ESCs.
Therefore, to realize the potential of ESCs in human cell therapy, it is critical
to understand the mechanisms how ESCs activate DNA damage response and DNA repair
to maintain genomic stability, which is a prerequisite for their use in human
therapy. In this context, it has been shown that ESCs harbor much fewer
spontaneous mutations than somatic cells. Consistent with the finding that ESCs
are genetically more stable than somatic cells, recent studies have indicated
that ESCs can mount more robust DNA damage responses and DNA repair than somatic
cells to ensure their genomic integrity.
PMID- 27614629
TI - Anterior disco-osteo-arterial conflict as a cause of intersegmental arterial flow
impairment and spinal cord ischemia.
AB - INTRODUCTION: This article describes anterior disco-osteo-arterial conflict as an
insofar unsuspected mechanism of arterial flow impairment potentially leading to
spinal cord ischemia and infarction. METHODS: The anterior disco-osteo-arterial
conflict described in this report is illustrated with angiographic observations
of patients presenting with spinal cord ischemia documented by MRI, and
radiculomedullary flow impairment diagnosed by spinal digital subtraction
angiography and spinal CTA. RESULTS: Proximal intersegmental artery flow
impairment was found in association with anterior disc bulging and anterior
osteophytic formation, alone or in combination. Patients either presented with an
initial acute medullary syndrome or with a long-standing history of spinal
claudication with acute secondary pejoration. CONCLUSION: Spinal ischemia can be
the result of intersegmental and radiculomedullary flow impairment caused by an
anterior disco-osteo-arterial conflict.
PMID- 27614630
TI - Effect of non-surgical periodontal treatment by full-mouth disinfection or
scaling and root planing per quadrant in halitosis-a randomized controlled
clinical trial.
AB - OBJECTIVE: The objective of this study was to compare the effect of one-stage
full-mouth disinfection (FMD) and conventional quadrant scaling in four weekly
sessions (QS) on periodontal clinical parameters and halitosis among individuals
with advanced chronic periodontitis. MATERIALS AND METHODS: In this randomized
controlled clinical trial, 30 individuals were divided into two groups: FMD (n =
15) and QS (n = 15). The following data were collected at the baseline and 90
days after treatment: plaque index, tongue-coating index (TCI), bleeding on
probing, probing depth, and clinical attachment level. Halimetry was performed by
the organoleptic method, and the levels of volatile sulfur compounds (H2S and
CH3SH) were measured by gas chromatography. The Chi-square, Fisher's exact, the
Mann-Whitney, the McNemar, and the Wilcoxon tests were used for statistical
analysis. RESULTS: Both groups showed statistically significant improvements in
periodontal clinical parameters, reduction in TCI, organoleptic scores, and in
CH3SH levels between times. However, major reduction was observed in FMD group.
CONCLUSION: Non-surgical periodontal therapy, regardless of the protocol, was
effective in improving periodontal clinical status of individuals, decreasing
organoleptic scores and CH3SH levels between times, as well as reducing
halitosis. CLINICAL RELEVANCE: This study contributed to the knowledge that non
surgical periodontal therapy, whether by FMD or QS, was effective in reducing
halitosis in individuals with advanced chronic periodontitis.
PMID- 27614631
TI - Polymorphisms of ICAM-1 and IL-6 genes related to endometriosis in a sample of
Brazilian women.
AB - PURPOSE: This study investigated the possibility of K469E (rs5498) and G241R
(rs1799969) polymorphisms, in ICAM-1 gene, and G634C (rs1800796), in IL-6 gene,
being associated with the occurrence of endometriosis in a sample of Brazilian
women. METHODS: We genotyped 200 women (100 in control group and 100 in
endometriosis group) by PCR-RFLP technique for G634C, K469E, and G241R
polymorphisms. RESULTS: No significant difference was observed in genotypic
frequency between control and endometriosis groups for G634C and K469E
polymorphisms (p = 0.61 and p = 0.22, respectively). In addition, no significant
difference between stages I-II and III-IV of the disease was found for both SNPs
(p = 0.63 and p = 0.24, respectively). All individuals were wild homozygotes for
G241R polymorphism. CONCLUSION: This study suggests that polymorphisms K469E,
G241R, and G634C are not associated with increased susceptibility to
endometriosis in Brazilian women.
PMID- 27614632
TI - Ultrastructure of cytoplasmic fragments in human cleavage stage embryos.
AB - PURPOSE: The goal of this study was to evaluate the ultrastructure of cytoplasmic
fragments along with the effect of cytoplasmic fragment and perivitelline space
coarse granulation removal (cosmetic microsurgery) from embryos before embryo
transfer on ART outcomes. METHODS: One hundred and fifty intracytoplasmic sperm
injection cycles with male factor infertility were included in this prospective
study. Patients were divided into three groups of case (n = 50), sham (n = 50),
and control (n = 50). Embryos with 10-50 % fragmentation were included in this
study. Cosmetic microsurgery and zona assisted hatching were only performed in
case and sham groups respectively. Extracted fragments were evaluated
ultrastructurally by transmission electron microscopy (TEM). Rates of clinical
pregnancy, live birth, miscarriage, multiple pregnancies, and congenital anomaly
in the three groups were also compared. RESULTS: Micrographs from TEM showed that
mitochondria were the most abundant structures found in the fragments along with
mitochondria-vesicle complexes, Golgi apparatus, primary lysosomes, and vacuoles.
There were no significant differences in demographic characteristics, laboratory
and clinical data, or embryo morphological features between the groups. The rate
of clinical pregnancy in control, sham, and case groups had no significant
differences (24, 18, and 18 %, respectively). The rates of live birth,
miscarriage, multiple pregnancy, and congenital anomaly were also similar between
the different groups. CONCLUSIONS: Our data demonstrated that cosmetic
microsurgery on preimplantation embryos had no beneficial effect on ART outcomes
in unselected groups of patients. As mitochondria are the most abundant
organelles found in cytoplasmic fragments, fragment removal should be performed
with more caution in embryos with moderate fragmentation.
PMID- 27614634
TI - Building a model to increase live birth rate through patient-specific
optimization of embryo transfer day.
AB - PURPOSE: Many practices are moving away from cleavage-stage transfer in favor of
blastocyst transfer. The purpose of this study is to evaluate how the overall
live birth rate for fresh IVF cycles may increase by optimizing the day of
transfer for each patient. METHODS: This is a retrospective cohort study of 1225
first fresh autologous IVF cycles performed between May 2012 and November 2013.
Stepwise logistic regression was used to determine characteristics associated
with live birth following cleavage-stage versus blastocyst transfer. The optimal
transfer day (i.e., the day that maximized the odds of live birth) was determined
for each patient, and the actual live birth rate was compared with the projected
rate had each patient undergone transfer on her optimal day. RESULTS: With
transfer on the optimal day for each patient, the overall birth rate would have
increased from its actual value of 34.8 % to a projected 43.0 %, a 24 % increase.
The majority of this increase (21 %) was due to optimization of patients who
underwent cleavage-stage transfer but had a higher projected birth rate from
blastocyst transfer. These patients were older (37.8 versus 36.0 years, p < 0.01)
and had more follicles >=18 mm than patients who should have remained with a
cleavage-stage transfer. CONCLUSIONS: A model can be built enabling patient
specific identification of optimal transfer day; within this discovery cohort,
such optimization was estimated to increase live birth following a fresh transfer
by 24 %. This study suggests blastocyst transfer should be more widely offered;
however, there remain patients for whom a cleavage-stage transfer may yield
better outcomes.
PMID- 27614635
TI - Computational study of H-abstraction reactions from CH3OCH2CH2Cl/CH3CH2OCH2CH2Cl
by Cl atom and OH radical and fate of alkoxy radicals.
AB - : Multichannel gas-phase reactions of CH3OCH2CH2Cl/CH3CH2OCH2CH2Cl with chlorine
atom and hydroxyl radical have been investigated using ab initio method and
canonical variational transition-state dynamic computations with the small
curvature tunneling correction. Further energetic information is refined by the
coupled-cluster calculations with single and double excitations (CCSD)(T) method.
Both hydrogen abstraction and displacement processes are carried out at the same
level. Our results reveal that H-abstraction from the -OCH2- group is the
dominant channel for CH3OCH2CH2Cl by OH radical or Cl atom, and from alpha-CH2 of
the group CH3CH2- is predominate for the reaction CH3CH2OCH2CH2Cl with Cl/OH. The
contribution of displacement processes may be unimportant due to the high
barriers. The values of the calculated rate constants reproduce remarkably well
the available experiment data. Standard enthalpies of formation for reactants and
product radicals are calculated by isodesmic reactions. The Arrhenius expressions
are given within 220-1200 K. The atmospheric lifetime, ozone depleting potential
(ODP), ozone formation potential (OFP), and global warming potential (GWP) of
CH3OCH2CH2Cl/CH3CH2OCH2CH2Cl are investigated. Meanwhile, the atmospheric fate of
the alkoxy radicals are also researched using the same level of theory. To shed
light on the atmospheric degradation, a mechanistic study is obtained, which
indicates that reaction with O2 is the dominant path for the decomposition of
CH3OCH(O*)CH2Cl, the C-C bond scission reaction is the primary reaction path in
the consumption of CH3CH(O*)OCH2CH2Cl in the atmosphere. HIGHLIGHTS: Ab initio
method and canonical variational transition-state theory are employed to study
the kinetic nature of hydrogen abstraction reactions of
CH3OCH2CH2Cl/CH3CH2OCH2CH2Cl with Cl atom and OH radical and fate of alkoxy
radicals (CH3OCH(O*)CH2Cl/CH3CH(O*)OCH2CH2Cl).
PMID- 27614633
TI - Protein expression in human cumulus cells as an indicator of blastocyst formation
and pregnancy success.
AB - PURPOSE: The goal for the present study was to implement a technique for protein
extraction and identification in human cumulus cells (CCs). METHODS: Forty
samples of CCs were collected after ovum pick-up from patients undergoing
intracytoplasmic sperm injection (ICSI). Samples were split into the blastocyst
group (n = 10), including patients in which all embryos converted into
blastocysts, and the non-blastocyst group (n = 10), including patients in which
none of the embryos reached the blastocyst stage or the positive-pregnancy (n =
10) and negative-pregnancy group (n = 10). Proteins were extracted and injected
into a liquid chromatography system coupled to a mass spectrometer. The spectra
were processed and used to search a database. RESULTS: There were 87 different
proteins in samples from the blastocyst and non-blastocyst groups, in which 30
were exclusively expressed in the blastocyst group and 17 in the non-blastocyst
group. Among the 72 proteins detected in the pregnancy groups, 19 were
exclusively expressed in the positive, and 16 were exclusively expressed in the
negative-pregnancy group. CONCLUSIONS: CC proteomics may be useful for predicting
pregnancy success and the identification of patients that should be included in
extended embryo culture programs.
PMID- 27614636
TI - Distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons
(PAHs) in surface water in industrial affected areas of the Three Gorges
Reservoir, China.
AB - Water samples were collected from wastewater treatment plant (WWTP), drain water
(DW), major tributaries (MT), and main course of the Yangtze River (MY) in areas
of three industrial parks (IPs) in Chongqing city in the Three Gorges Reservoir
(TGR). Sixteen EPA priority polycyclic aromatic hydrocarbon (PAH) pollutants were
quantified to identify the effects of industrial activities on water quality of
the TGR. The results showed that 11 individual PAHs were quantified and 5 PAHs
(naphthalene (Nap), acenaphthylene (Acy), benzo[k]fluoranthene (BkF),
indeno[1,2,3-cd]pyrene (InP), and benzo[g,h,i]perylene (BgP)) were under
detection limits in all of the water samples. Three-ring and four-ring PAHs were
the most detected PAHs. Concentrations of individual PAHs were in the range of
not detected (nd) to 24.3 ng/L. Total PAH concentrations for each site ranged
from nd to 42.9 ng/L and were lower compared to those in other studies. The mean
PAH concentrations for sites WWTP, DW, MT, and MY showed as follows: DW (25.9
ng/L) > MY (15.5 ng/L) > MT (14.0 ng/L) > WWTP (9.3 ng/L), and DW contains the
highest PAH concentrations. Source identification ratios showed that petroleum
and combustion of biomass coal and petroleum were the main sources of PAHs. The
results of potential ecosystem risk assessment indicated that, although PAH
concentrations in MT and MY are likely harmless to ecosystem, contaminations of
PAHs in DW were listed as middle levels and some management strategies and
remediation actions, like strengthen clean production processes and banning
illegal sewage discharging activities, etc., should be taken to lighten the
ecosystem risk caused by PAHs especially risks caused by water discharging
drains.
PMID- 27614637
TI - Assessment of trace metal air pollution in Paris using slurry-TXRF analysis on
cemetery mosses.
AB - Mosses are useful, ubiquitous accumulation biomonitors and as such can be used
for biomonitoring surveys. However, the biomonitoring of atmospheric pollution
can be compromised in urban contexts if the targeted biomonitors are regularly
disturbed, irregularly distributed, or are difficult to access. Here, we test the
hypothesis that cemeteries are appropriate moss sampling sites for the evaluation
of air pollution in urban areas. We sampled mosses growing on gravestones in 21
urban and peri-urban cemeteries in the Paris metropolitan area. We focused on
Grimmia pulvinata (Hedwig) Smith, a species abundantly found in all studied
cemeteries and very common in Europe. The concentration of Al, As, Br, Ca, Ce,
Cl, Cr, Cu, Fe, K, Mn, Ni, V, P, Pb, Rb, S, Sr, Ti, and Zn was determined by a
total reflection X-ray fluorescence technique coupled with a slurry sampling
method (slurry-TXRF). This method avoids a digestion step, reduces the risk of
sample contamination, and works even at low sample quantities. Elemental markers
of road traffic indicated that the highest polluted cemeteries were located near
the highly frequented Parisian ring road and under the influence of prevailing
winds. The sites with the lowest pollution were found not only in the peri-urban
cemeteries, adjoining forest or farming landscapes, but also in the large and
relatively wooded cemeteries located in the center of Paris. Our results suggest
that (1) slurry-TXRF might be successfully used with moss material, (2) G.
pulvinata might be a good biomonitor of trace metals air pollution in urban
context, and (3) cemetery moss sampling could be a useful complement for
monitoring urban areas. Graphical abstract We tested the hypothesis that
cemeteries are appropriate moss sampling sites for the evaluation of air
pollution in urban areas. We sampled 110 moss cushions (Grimmia pulvinata)
growing on gravestones in 21 urban and peri-urban cemeteries in the Paris
metropolitan area. The concentration of 20 elements in mosses was determined by a
total reflection X-ray fluorescence technique coupled with a slurry sampling
method. Statistical analysis revealed that: - Urbanized Parisian areas crossed by
traffic roads have the highest polluted cemeteries with a strong influence of
main wind direction on the distribution of air pollutants - As expected, small
cemeteries with low tree density were heavily polluted - Less obvious, large
green spaces such as large cemeteries (Pere Lachaise, Montmartre, Montparnasse)
in the center of a dense metropolis like Paris present the same level of
atmospheric trace metal pollution as cemeteries in less urbanized areas or
nearing a very large forest. This suggests that even in densely urbanized areas,
there is more spatial variability in pollution distribution than usually assumed
and that large urban areas with low traffic and green filters such as trees are
likely to intercept air pollutants.
PMID- 27614638
TI - Perovskite-type titanate zirconate as photocatalyst for textile wastewater
treatment.
AB - Calcium titanate zirconate, Ca(Ti(1-x)Zrx)O3 (CZT), powders have been synthesised
by the polymeric precursor method. The structural analysis of the CZT powders was
monitored by X-ray diffraction (XRD), photoacoustic spectroscopy (PAS) and
textural analysis. The photocatalytic properties were evaluated by methylene blue
(MB) decomposition and real textile wastewater (RTW) combined treatment
(coagulation/flocculation/photocatalysis). Chemical oxygen demand (COD) of RTW
was successfully reduced from 6195 mg L-1 (untreated) to 662 mg L-1 after
coagulation/flocculation with a tannin-based coagulant (Tanfloc(r)) and finally
to 471 mg L-1 after combined treatment (coagulation/flocculation/photocatalysis)
applying ultraviolet radiation and CaTiO3 as photocatalyst.
PMID- 27614639
TI - Heavy metal in sediments of Ziya River in northern China: distribution, potential
risks, and source apportionment.
AB - The concentration partitioning between the sediment particle and the interstitial
water phase plays an important role in controlling the toxicity of heavy metals
in aquatic systems. The aim of this study was to assess the sediment quality in a
polluted area of the Ziya River, Northern China. The contamination potential and
bioavailability of six metals were determined from the concentrations of total
metals and the bioavailable fractions. The results showed that the concentrations
of Cr, Cu, Ni, Zn, and Pb exceeded the probable effect concentration at several
sites. The high geoaccumulation indices showed that the sediments were seriously
contaminated by Cd. The ratio of acid-volatile sulfide (AVS) to simultaneously
extracted metal (SEM) was higher than 1, which indicated that the availability of
metals in sediments was low. The risk assessment of interstitial waters confirmed
that there was little chance of release of metals associated with acid-volatile
sulfide into the water column. Values of the interstitial water criteria toxicity
unit indicated that none of the concentrations of the studied metals exceeded the
corresponding water quality thresholds of the US Environmental Protection Agency.
Positive matrix factorization showed that the major sources of metals were
related to anthropogenic activities. Further, if assessments are based on total
heavy metal concentrations, the toxicity of heavy metals in sediment may be
overestimated.
PMID- 27614640
TI - Microplastics affect assimilation efficiency in the freshwater amphipod Gammarus
fossarum.
AB - An important issue in assessing microplastics is whether this newly emerging type
of pollution affects freshwater invertebrates. This study was designed to examine
the interactions between the amphipod Gammarus fossarum and two types of
microplastics. To determine the ingestion and egestion of polyamide (PA) fibres
(500 * 20 MUm), amphipods were exposed to four concentrations (100, 540, 2680,
13,380 PA fibres cm-2 base area of glass beakers) and four exposure times (0.5,
2, 8, 32 h) as well as four post-exposure times (1, 2, 4, 16 h). We demonstrate a
positive correlation between concentration and ingestion of PA fibres. Fibres
were found in the gut after 0.5 h of exposure. Egestion was rapid and the
digestive tract was empty 16 h after exposure ended. To investigate whether
polystyrene (PS) beads (1.6 MUm) can be taken up in the epithelial cells of the
gut and the midgut glands, four concentrations (500, 2500, 12,500, 60,000 PS
beads mL-1) were tested. Cryosections exhibited fluorescent PS beads only within
the gut lumen. In a 28-day feeding experiment with both, fibres and beads, we
studied the amphipod's feeding rate, assimilation efficiency and wet weight
change. The exposure to PA fibres (2680 PA fibres cm-2 base area of glass
beakers) significantly reduced the assimilation efficiency of the animals. While
both tested polymer types are ingested and egested, PA fibres can impair the
health and ecological functions of freshwater amphipods under continuous
exposure.
PMID- 27614641
TI - A 59-year sedimentary record of metal pollution in the sediment core from the
Huaihe River, Huainan, Anhui, China.
AB - An approximately 59-year (1955-2014) sedimentary record of metal elements (Cu,
Pb, Zn, Ni, Co, Mn, and Fe) in a sediment core, collected from the Huaihe River,
Huainan City, Anhui Province, China, was reconstructed by using 210Pb
geochronology. Copper, Zn, Ni, Co, and Mn evaluated by enrichment factor (EF)
indicated minor contamination due to water pollution accidents of the Huaihe
River that occurred in 1990s and 2004. Lead presented the most severe pollution
among the metals studied, especially during 1957-1974. The use of leaded petrol
and atmospheric deposition of coal combustion flue gases could have contributed
to Pb contamination. In spite of the general good quality (mean sediment
pollution index (SPI) 35.69) of the sediment core evaluated by SPI based on the
principal component analysis, worse sediment qualities in the upper section (<6
cm, 2004) were still observed, suggesting intensive human activities causing the
increasing concentrations of metals in recent decades.
PMID- 27614642
TI - Metabolic and endocrine effects of bisphenol A exposure in market seller women
with polycystic ovary syndrome.
AB - Bisphenol A (BPA) is one of the synthetic monomer which can be found in the
environment. Limited animal and human studies have demonstrated that BPA alters
endocrine and or metabolic functions. The aims of the present study were to
evaluate serum BPA level in marketing seller women with polycystic ovary syndrome
(PCOS) and hormonal and metabolic effects of this exposure compared to a control
paired group. In a case-control study, 62 PCOS women who work as marketing
sellers and 62 healthy women with similar jobs were included. The two groups were
body mass index (BMI)- and age-matched. Serum samples were analyzed for BPA
content, fasting blood sugar (FBS), triglyceride, cholesterol, HDL and LDL
levels, thyroid stimulating hormone (TSH) concentration, and LH:FSH ratio.
Significant higher serum BPA content (0.48 +/- 0.08 vs. 0.16 +/- 0.04 ng/ml),
triglyceride (103.05 +/- 13.10 vs. 91.65 +/- 12.52 mg/dl), cholesterol (165.05 +/
10.79 vs. 161.21 +/- 10.31 mg/dl) levels and LH:FSH ratio (3.64 +/- 0.86 vs.
0.62 +/- 0.14) and significant lower TSH concentration (1.56 +/- 0.68 vs. 2.15 +/
1.09 IU/ml) were detected in case against control group, respectively (P <
0.05). No significant differences were detected in FBS, LDL, and HDL levels
between the two groups. Also, there were no significant associations between
serum TSH concentration and BPA level neither in case (P = 0.269) nor in control
(P = 0.532) groups. In BPA-exposed PCOS women, BPA level was higher than healthy
women and this difference maybe the cause of significant differences in levels of
triglyceride, cholesterol, TSH, and LH:FSH ratio. These observations confirm the
potential role of BPA in PCOS pathophysiology.
PMID- 27614643
TI - Effects of alkaline and bioorganic amendments on cadmium, lead, zinc, and
nutrient accumulation in brown rice and grain yield in acidic paddy fields
contaminated with a mixture of heavy metals.
AB - Paddy soils and rice (Oryza sativa L.) contaminated by mixed heavy metals have
given rise to great concern. Field experiments were conducted over two
cultivation seasons to study the effects of steel slag (SS), fly ash (FA),
limestone (LS), bioorganic fertilizer (BF), and the combination of SS and BF
(SSBF) on rice grain yield, Cd, Pb, and Zn and nutrient accumulation in brown
rice, bioavailability of Cd, Pb, and Zn in soil as well as soil properties (pH
and catalase), at two acidic paddy fields contaminated with mixed heavy metals
(Cd, Pb, and Zn). Compared to the controls, SS, LS, and SSBF at both low and high
additions significantly elevated soil pH over both cultivation seasons. The high
treatments of SS and SSBF markedly increased grain yields, the accumulation of P
and Ca in brown rice and soil catalase activities in the first cultivation
season. The most striking result was from SS application (4.0 t ha-1) that
consistently and significantly reduced the soil bioavailability of Cd, Pb, and Zn
by 38.5-91.2 % and the concentrations of Cd and Pb in brown rice by 20.9-50.9 %
in the two soils over both cultivation seasons. LS addition (4.0 t ha-1) also
markedly reduced the bioavailable Cd, Pb, and Zn in soil and the Cd
concentrations in brown rice. BF remobilized soil Cd and Pb leading to more
accumulation of these metals in brown rice. The results showed that steel slag
was most effective in the remediation of acidic paddy soils contaminated with
mixed heavy metals.
PMID- 27614644
TI - Mobility and plant availability of risk elements in soil after long-term
application of farmyard manure.
AB - Crop rotation long-term field experiments were established in 1955 and 1956 at
three locations in the Czech Republic (Caslav, Ivanovice, and Lukavec) differing
in their climatic and soil physicochemical properties. The effect of long-term
application of farmyard manure and farmyard manure + NPK treatments on plant
available, easily mobilizable, potentially mobilizable, and pseudo-total contents
of arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) contents in
soils (in 2013) as well as the uptake of these elements by winter wheat (Triticum
aestivum L.) grain and straw were analyzed in the two following seasons: 2012 and
2013. The treatments resulted in increasing the soil pH level when compared to
the control, but the cation exchange capacity remained unchanged. Although all
fertilizers were applied for six decades, the pseudo-total concentration elements
in both the soil and wheat plants stayed far below those of the Czech and
European threshold limits for agricultural soils and cereals for human nutrition
and feedstuff. Although the mobile pools of As, Cu, and Zn were slightly changed
at the treated soils, these changes were not related to the element uptake by the
wheat plants. Moreover, the effect of the location and growing season was more
decisive for the differences in soil and plant element contents than for the
individual treatments. Thus, the long-term application of farmyard manure did not
result in any substantial change in risk element contents in both soils and
winter wheat plants.
PMID- 27614645
TI - Monitoring the clean-up operation of agricultural fields flooded with red mud in
Hungary.
AB - In the course of the clean-up operation after the red mud inundation in 2010, red
mud was removed from the soil surface in places where the layer was more than 5
cm deep. Before its removal, the red mud seeped into the soil. In 2012, soil
samples were taken from depths of 0 to 20 and 20 to 40 cm on some of the affected
areas. The parameters investigated were pH, organic matter, salt%, and the total
and mobile fractions of various elements. The values recorded in 2012 were
compared with those measured immediately after the removal of the red mud in 2010
and with the background and clean-up target concentrations. The pH values
remained below the designated limit, while the salt content only exhibited values
in the weakly salty range on areas at the greatest distance from the dam. In the
central part of the inundated area, total Na contents above the 900 mg/kg target
value were observed, but the Na content in the 0-20-cm layer generally exhibited
a decrease due to leaching. The pH and As concentration also showed a decline on
several areas compared with the values recorded in 2010. Total As and Co contents
in excess of the target values were recorded on the lowest-lying part of the
flooded area, probably because the finest red mud particles were deposited the
furthest from the dam, where they seeped into the soil. Nevertheless, the
mobility and plant availability of both elements remained moderate. The total
contents of both Co and Mo, however, exhibited a significant rise compared with
both the background value and the 2010 data. The monitoring of the cleaned-up
areas showed that after a 2-year period element concentrations that exceeded the
target values and could be attributed to the red mud pollution were only
detectable on the lowest-lying areas.
PMID- 27614646
TI - Organic materials retain high proportion of protons, iron and aluminium from acid
sulphate soil drainage water with little subsequent release.
AB - When previously oxidised acid sulphate soils are leached, they can release large
amounts of protons and metals, which threaten the surrounding environment. To
minimise the impact of the acidic leachate, protons and metals have to be
retained before the drainage water reaches surrounding waterways. One possible
amelioration strategy is to pass drainage water through permeable reactive
barriers. The suitability of organic materials for such barriers was tested.
Eight organic materials including two plant residues, compost and five biochars
differing in feedstock and production temperature were finely ground and filled
into PVC cores at 3.5 g dry wt/core. Field-collected acidic drainage water (pH 3,
Al 22 mg L-1 and Fe 48 mg L-1) was applied in six leaching events followed by six
leaching events with reverse osmosis (RO) water (45 mL/event). Compost and
biochars increased the leachate pH by up to 4.5 units and had a high retention
capacity for metals. The metal and proton release during subsequent leaching with
RO water was very small, cumulatively only 0.05-0.8 % of retained metals and
protons. Retention was lower in the two plant residues, particularly wheat straw,
which raised leachate pH by 2 units only in the first leaching event with
drainage water, but had little effect on leachate pH in the following leaching
events. It can be concluded that organic materials and particularly biochars and
compost have the potential to be used in acid drainage treatment to remove and
retain protons and metals.
PMID- 27614647
TI - Free radical reaction characteristics of coal low-temperature oxidation and its
inhibition method.
AB - Study on the mechanism of coal spontaneous combustion is significant for
controlling fire disasters due to coal spontaneous combustion. The free radical
reactions can explain the chemical process of coal at low-temperature oxidation.
Electron spin resonance (ESR) spectroscopy was used to measure the change rules
of the different sorts and different granularity of coal directly; ESR
spectroscopy chart of free radicals following the changes of temperatures was
compared by the coal samples applying air and blowing nitrogen, original coal
samples, dry coal samples, and demineralized coal samples. The fragmentation
process was the key factor of producing and initiating free radical reactions.
Oxygen, moisture, and mineral accelerated the free radical reactions. Combination
of the free radical reaction mechanism, the mechanical fragmentation leaded to
the elevated CO concentration, fracturing of coal pillar was more prone to
spontaneous combustion, and spontaneous combustion in goaf accounted for a large
proportion of the fire in the mine were explained. The method of added
diphenylamine can inhibit the self-oxidation of coal effectively, the action
mechanism of diphenylamine was analyzed by free radical chain reaction, and this
research can offer new method for the development of new flame retardant.
PMID- 27614648
TI - Enhanced adsorption of methylene blue by citric acid modification of biochar
derived from water hyacinth (Eichornia crassipes).
AB - In this work, a novel potential adsorbent, citric acid (CA)-modified biochar,
named as CAWB, was obtained from water hyacinth biomass by slow pyrolysis in a N2
environment at 300 degrees C. The CA modification focused on enhancing the
contaminants adsorption capacity of biochar pyrolyzed at relatively low
temperature. Over 90 % of the total methylene blue (MB) could be removed at the
first 60 min by CAWB, and the maximum MB adsorption capacity could reach to 395
mg g-1. The physicochemical properties of CAWB was examined by FTIR, XPS, SEM,
and BET analysis. The results indicated that the additional carboxyl groups were
introduced to the surface of CAWB via the esterification reaction with CA, which
played a significant role in the adsorption of MB. Batch adsorption studies
showed that the initial MB concentration, solution pH, background ionic strength,
and temperature could affect the removal efficiency obviously. The adsorption
process could be well described by the pseudo-second-order kinetic model and
Langmuir isotherm. Thermodynamic analysis revealed that the MB adsorption onto
CAWB was an endothermic and spontaneous process. The regeneration study revealed
that CAWB still exhibited an excellent regeneration and adsorption performance
after multiple cycle adsorptions. The adsorption experiments of actual dye
wastewater by CAWB suggested that it had a great potential in environmental
application.
PMID- 27614649
TI - Preparation of transition metal composite graphite felt cathode for efficient
heterogeneous electro-Fenton process.
AB - A composite graphite felt (GF) modified with transition metal was fabricated and
used as cathode in heterogeneous electro-Fenton (EF) for methyl orange (MO)
degradation. Characterized by scanning electron microscopy (SEM) and X-ray
photoelectron spectroscopy (XPS), the morphology and surface physicochemical
properties of the cathodes after modification were observed considerably changed.
After loading metals, the current response became higher, the accumulation of
H2O2 and the degradation efficiency of MO were improved. Under the same
conditions, GF-Co had the highest catalytic activity for electro-reduction of O2
to H2O2 and MO degradation. At pH 3, 99 % of MO degradation efficiency was
obtained using GF-Co after 120 min treatment and even at initial pH 9, 82 % of
that was obtained. TOC removal efficiency reached 93.8 % using GF-Co at pH 3
after 120 min treatment while that was 12.3 % using GF. After ten-time runs, the
mineralization ratio of the GF-Co was still 89.5 %, suggesting that GF-Co was
very promising for wastewater treatment. The addition of isopropanol proved that
.OH played an important role in degradation of MO.
PMID- 27614650
TI - Assessment of metal retention in newly constructed highway embankments.
AB - Newly constructed embankments should provide both a specific bearing capacity to
enable trafficability in emergency cases and a sufficient pollutant retention
capacity to protect the groundwater. A number of lysimeters were installed along
the A115 highway to determine total and dissolved metal concentrations in road
runoff and in the soil solution of newly constructed embankments. Dissolved
concentrations in soil solution of the embankments did not exceed the trigger
values of the German legislation. Depending on the metal, total concentrations in
soil solution were more than twice as high as dissolved concentrations. The high
infiltration rates lead to increased groundwater recharge beneath the embankments
(up to 4100 mm a-1). Although metal concentrations were not problematic from the
legislators' point of view, the elevated infiltration rates beside the road
facilitated the transfer of high metal loads into deeper soil layers and
potentially into the groundwater as well.
PMID- 27614651
TI - Heavy metal speciation, risk, and bioavailability in the sediments of rivers with
different pollution sources and intensity.
AB - A comprehensive analysis of heavy metal speciation, risk, and bioavailability in
the sediments of three rivers in northern China (Shaocun River (SR), Wangyang
River (WR), and Xiao River (XR)) was conducted. The results showed that higher
pollution input resulting from urbanization and industrialization caused higher
heavy metal contents and bioavailable proportion in the studied sediments. Total
contents of all studied metals (Cr, Cu, Ni, Pb, and Zn) in the sediments of SR,
WR, and XR were 270.31, 902.62, and 2367.46 mg/kg, respectively. The average
percentages of bioavailable fractions were 31.16, 61.73, and 81.69 %,
respectively. Cr, Ni, and Pb were all mainly observed in the B4 (residual)
fraction in the studied sediments, with an average percentage of 42.03, 48.19,
and 55.08 %, respectively. Cu was mainly observed in the B2 (reducible) fraction
(40.53 %). Zn was mainly observed in the B1 (exchangeable/acid soluble/carbonate)
fraction (36.01 %), resulting in medium or high risk associated with Zn in the
sediments of SR, WR, and XR. Sedimentary heavy metal risk and bioavailability
associated with regional urbanization and industrialization should be taken into
consideration with respect to the health of aquatic ecosystems.
PMID- 27614652
TI - In situ stabilization of heavy metals in multiple-metal contaminated paddy soil
using different steel slag-based silicon fertilizer.
AB - Steel slag has been widely used as amendment and silicon fertilizer to alleviate
the mobility and bioavailability of heavy metals in soil. The objective of this
study was to evaluate the influence of particle size, composition, and
application rate of slag on metal immobilization in acidic soil, metals uptake by
rice and rice growth. The results indicated that application of slag increased
soil pH, plant-available silicon concentrations in soil, and decreased the
bioavailability of metals compared with control treatment, whereas pulverous slag
(S1) was more effective than granular slag (S2 and S3). The acid-extractable
fraction of Cd in the spiked soil was significantly decreased with application of
S1 at rates of 1 and 3 %, acid-extractable fractions of Cu and Zn were decreased
when treated at 3 %. Use of S1 at both rates resulted in significantly lower Cd,
Cu, and Zn concentrations in rice tissues than in controls by 82.6-92.9, 88.4
95.6, and 67.4-81.4 %, respectively. However, use of pulverous slag at 1 %
significantly promotes rice growth, restricted rice growth when treated at 3 %.
Thus, the results explained that reduced particle size and suitable application
rate of slag could be beneficial to rice growth and metals stabilization.
PMID- 27614653
TI - Marital Age Disparity Among Orphaned Young Women and Their Husbands: A Mixed
Methods Study in Rural Zimbabwe.
AB - Our study reports the results from a mixed method study comparing age-similar
(AS) marriages of orphaned young women to age disparate (AD) marriages, defined
as spousal age difference of 5 or more years. Research in Zimbabwe and sub
Saharan Africa suggests that AD sexual relationships between older men and young
women increase the risk for HIV but few studies have examined this association
among married couples or explored why young women marry much older men. In this
study, a total of 35 orphaned young women aged 17-26 years in rural Zimbabwe
participated in semi-structured interviews during 2012-2013. Twenty-four were in
AD marriages and 11 AS. All had participated in a 5-year HIV prevention trial,
during which they had married and dropped out of school. We examined two research
questions: were AD wives more likely than AS to cite economic considerations as a
reason to marry, and were AD marriages associated with different health and
economic outcomes compared to AS? Our results showed that the reasons the women
married were essentially the same among the two groups; economic considerations
for marriage were uncommon. Nevertheless, AD wives generally fared somewhat
better than AS wives on economic and well-being measures. HIV prevalence was
similar; however, the AD group accounted for all five cases of herpes simplex
virus-2. Findings suggest the complexity of sexual and reproductive health in
rural Africa, where AD marriages are common and accepted. The challenge for
primary prevention is to develop strategies to mitigate the risk of sexually
transmitted infections, as well as the potential abuse of young women, within the
appropriate cultural context.
PMID- 27614655
TI - Modernizing Evolutionary Anthropology : Introduction to the Special Issue.
AB - Evolutionary anthropology has traditionally focused on the study of small-scale,
largely self-sufficient societies. The increasing rarity of these societies
underscores the importance of such research yet also suggests the need to
understand the processes by which such societies are being lost-what we call
"modernization"-and the effects of these processes on human behavior and biology.
In this article, we discuss recent efforts by evolutionary anthropologists to
incorporate modernization into their research and the challenges and rewards that
follow. Advantages include that these studies allow for explicit testing of
hypotheses that explore how behavior and biology change in conjunction with
changes in social, economic, and ecological factors. In addition, modernization
often provides a source of "natural experiments" since it may proceed in a
piecemeal fashion through a population. Challenges arise, however, in association
with reduced variability in fitness proxies such as fertility, and with the
increasing use of relatively novel methodologies in evolutionary anthropology,
such as the analysis of secondary data. Confronting these challenges will require
careful consideration but will lead to an improved understanding of humanity. We
conclude that the study of modernization offers the prospect of developing a
richer evolutionary anthropology, by encompassing ultimate and proximate
explanations for behavior expressed across the full range of human societies.
PMID- 27614656
TI - Weight loss and decubitus duodenal ulcer in Parkinson's disease treated with
levodopa-carbidopa intestinal gel infusion.
AB - Apparently, unexplained weight loss is a common symptom experienced by patients
affected by Parkinson's disease, especially in those treated by levodopa
carbidopa infusion gel (LCIG) with a poor control of dyskinesias. Weight loss is
considered part of gastrointestinal dysfunction seen in patients affected by
Parkinson's disease, along with gastroparesis and reduced bowel peristalsis. In
patients treated with LCIG, weight loss needs to be accurately evaluated, because
of possible underlying life-threatening adverse events, like duodenum decubitus
ulcer.
PMID- 27614654
TI - HIV, Aging, and Viral Coinfections: Taking the Long View.
AB - Viral suppression of human immunodeficiency virus (HIV) with combination
antiviral therapy (cART) has led to increasing longevity but has not enabled a
complete return to health among aging HIV-infected individuals (HIV+). Viral
coinfections are prevalent in the HIV+ host and are implicated in cancer, liver
disease, and accelerated aging. We must move beyond a simplistic notion of HIV
becoming a "chronic controllable illness" and develop an understanding of how
viral suppression alters the natural history of HIV infection, especially at the
intersection of HIV with other common viral coinfections in the context of an
altered, aging immune system.
PMID- 27614658
TI - Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic
patients.
AB - AIMS/HYPOTHESIS: We have recently shown that adjunct prednisone shortens the time
taken to reach clinical stability (time to clinical stability, TTCS) in patients
with community-acquired pneumonia (CAP). Considering the hyperglycaemic effects
of prednisone, there are concerns about the efficacy and safety of this therapy
for diabetic patients with CAP. Our objective was to evaluate whether diabetes
and/or hyperglycaemia on admission to hospital has an influence on the effect of
corticosteroids on outcome in a well-defined cohort of patients with CAP.
METHODS: This is a preplanned subanalysis of a prospective randomised, double
blind placebo-controlled multicentre trial. Patients aged 18 years or older with
CAP were eligible and were recruited from seven tertiary care hospitals in
Switzerland within 24 h of presentation. Patients were randomised (1:1 ratio) to
receive either 50 mg of prednisone daily for 7 days or placebo. Allocation was
concealed with a prespecified computer-generated randomisation list. Patients,
treating physicians, investigators and data assessors were masked to treatment
allocation. The primary endpoint was TTCS; secondary endpoints were length of
stay, mortality, duration of antibiotic treatment, CAP complications and new
insulin requirement at day 30. Furthermore, we analysed whether these endpoints
were influenced by a glycaemic dysregulation during the study time. RESULTS: Of
802 patients randomised (n = 402 in the prednisone, n = 400 in the placebo
group), 726 patients were treated per protocol and included in this analysis (n =
362 in the prednisone, n = 364 in the placebo group). Nineteen per cent of 726
patients had diabetes mellitus (n = 66 in the prednisone group, n = 72 in the
placebo group). Adjunct prednisone shortened TTCS in diabetic and non-diabetic
patients (HR 1.65 [95% CI 1.16, 2.35], p = 0.007; 1.30 [95% CI 1.10, 1.53], p =
0.002) with no evidence for effect modification by diabetes in interaction
analysis (p = 0.44). No difference was found in other clinically relevant
endpoints. Although adjunct prednisone was associated with glycaemic
dysregulation, this did not translate into worse clinical outcomes in either
group, and there was no difference in secondary endpoints.
CONCLUSIONS/INTERPRETATION: The benefit of adjunct prednisone in CAP patients is
also valid for those with diabetes or hyperglycaemia on admission. Hyperglycaemia
in diabetic patients or due to adjunct prednisone did not have a negative effect
on outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT00973154 FUNDING : This
study was supported by a grant from the Swiss National Foundation and by the Nora
van Meeuwen Hafliger Stiftung and the Gottfried Julia Bangerter-Rhyner Stiftung.
PMID- 27614659
TI - Reliability, validity and responsiveness of the Greek MacDQoL individualized
measure of the impact of macular degeneration on quality of life.
AB - PURPOSE: To assess the psychometric properties of the Greek Macular Disease
Dependent Quality of Life Questionnaire (MacDQoL). METHODS: The MacDQoL was
translated in Greek and administered to 191 patients with neovascular age-related
macular degeneration (AMD). To assess validity, all patients completed the Greek
SF-12 health survey and underwent vision measurements. For test-retest
reliability, a subset of twenty participants completed the MacDQoL twice, 2 weeks
apart. Responsiveness was assessed on 102 patients who completed the MacDQoL at a
follow-up visit, 1 year later. Rasch analysis was used to assess the Greek
MacDQoL's response category functioning, precision, unidimensionality, targeting
and differential item functioning. RESULTS: Internal and test-retest reliability
of the average weighted impact (AWI) was 0.952 and 0.97, respectively. Test
retest reliability of MacDQoL items ranged from 0.78 to 0.99. Principal component
analysis revealed three subscales (activities, embarrassment and family life),
which were also confirmed by confirmatory factor analysis. Rasch analysis
revealed poor functionality of response categories and that was resolved by
collapsing response categories and using the impairment scores only. In terms of
convergent validity, the AWI and revised MacDQoL scales showed significant
correlations with SF-12 summary scales (rho = 0.21-0.30) and vision assessments
(rho = 0.31-0.46). Poorer AMD-related QoL at 1-year follow-up was associated with
deterioration in distance visual acuity and worse eye near visual acuity.
CONCLUSIONS: The Greek MacDQoL is a reliable, valid and sensitive to change in
vision instrument for assessing AMD patients' perceptions of QoL. However, Rasch
analysis revealed that its multiplicative rating scale is flawed. Scientific
measurement was restored with a number of revisions to the questionnaire.
PMID- 27614657
TI - Prescription opioid use disorder and heroin use among 12-34 year-olds in the
United States from 2002 to 2014.
PMID- 27614660
TI - Feasibility and full-course dosimetry of an intraoperatively placed multichannel
brachytherapy catheter for accelerated partial breast irradiation.
AB - PURPOSE: Determine feasibility and resultant dosimetry of an intraoperatively
placed multichannel intracavitary brachytherapy catheter for accelerated partial
breast irradiation (APBI). METHODS: Patients with breast cancer underwent
intraoperative brachytherapy catheter placement based on frozen section analysis
with immediate postoperative APBI. The planning target volume evaluation
(PTVEval) and organs at risk were contoured on daily pretreatment CT scans for
each patient, and the original treatment plan was applied to assess full-course
dosimetry. RESULTS: Of the first 21 patients consented for intraoperative
catheter placement, 20 (95%) were able to proceed with treatment as planned. The
mean volume of PTVEval receiving 90% of prescription dose (V90%) and mean
percentage of prescription dose to 90% of the PTVEval (D90%) on initial planning
were 96.7 (+/-1.1%) and 100.2 (+/-2.1%), respectively. Full-course dose coverage
remained excellent with a mean PTVEval V90% and D90% of 95.0 (+/-4.4%) and 100.2
(+/-9.6%), respectively. Mean full-course maximum dose constraints for chest wall
and skin were met by 70% and 95% of patients, respectively. Air accumulation >1
cc during treatment increased the risk of a daily fraction with PTVEval coverage
below goal (odds ratio, 9.8; p = 0.05), whereas those with applicators <0.5 cm
from the chest wall at planning were at risk of exceeding that organ's maximum
dose constraint on a daily fraction (odds ratio, 45; p = 0.02). CONCLUSIONS:
Intraoperative catheter placement and early initiation of APBI based on frozen
section pathology is feasible, yields acceptable dosimetry, and is an option for
completing breast conserving therapy in less than 10 days.
PMID- 27614661
TI - Salvage high-dose-rate brachytherapy for isolated vaginal recurrence of
endometrial cancer.
AB - PURPOSE: We have retrospectively analyzed the outcomes of high-dose-rate (HDR)
brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer.
METHODS AND MATERIALS: From 1997 to 2012, salvage HDR brachytherapy was performed
in 43 patients. The median age was 64 years (range, 41-88 years). HDR
brachytherapy was performed by interstitial brachytherapy in 34 patients (79%)
and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the
43 patients were treated with external beam radiotherapy. The median followup
period was 58 months (range, 6-179 months). RESULTS: The 5-year overall survival
(OS), progression-free survival (PFS), and local control rates (LC) were 84%,
52%, and 78%, respectively. Patients who received brachytherapy with external
beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23%
of the patients (6 of 26 patients) who received brachytherapy alone experienced
nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery
(G1-2 vs. G3) was found to be a significant prognostic factor for both OS and
PFS. The respective 5-year OS was 96% vs. 40% (p < 0.01), and the 5-year PFS was
58% vs. 0% (p < 0.01). Age (>=60 vs. <60) and modality (interstitial
brachytherapy vs. intracavity brachytherapy) were significant prognostic factors
for LC. The respective 5-year LC was 74% vs. 100% (p = 0.020) and 85% vs. 56% (p
= 0.035). CONCLUSIONS: HDR brachytherapy is effective and feasible in patients
with isolated vaginal recurrence of endometrial cancer. Pathologic grade, age,
and modality were significant prognostic factors.
PMID- 27614662
TI - Do improved patient recall and the provision of memory support enhance treatment
adherence?
AB - BACKGROUND AND OBJECTIVES: Patient adherence to psychosocial treatment is an
important but understudied topic. The aim of this study was to examine whether
better patient recall of treatment contents and therapist use of memory support
(MS) were associated with better treatment adherence. METHODS: Data were drawn
from a pilot randomized controlled trial. Participants were 48 individuals (mean
age = 44.27 years, 29 females) with Major Depressive Disorder randomized to
receive either Cognitive Therapy (CT) with an adjunctive Memory Support
Intervention (CT + Memory Support) or CT-as-usual. Therapist and patient ratings
of treatment adherence were collected during each treatment session. Patient
recall was assessed at mid-treatment. Therapist use of MS was manually coded for
a random selection of sessions. RESULTS: Patient recall was significantly
associated with better therapist and patient ratings of adherence. Therapist use
of Application, a specific MS strategy, predicted higher therapist ratings of
adherence. Attention Recruitment, another specific MS strategy, appeared to
attenuate the positive impact of session number on patient ratings of adherence.
Treatment groups, MS summary scores and other specific MS strategies were not
significantly associated with adherence. LIMITATIONS: The measure for treatment
adherence is in the process of being formally validated. Results were based on
small sample. CONCLUSIONS: These results support the importance of patient recall
in treatment adherence. Although collectively the effects of MS on treatment
adherence were not significant, the results support the use of certain specific
MS strategy (i.e., application) as a potential pathway to improve treatment
adherence. Larger-scale studies are needed to further examine these constructs.
PMID- 27614663
TI - Cognitive vulnerabilities in parents as a potential risk factor for anxiety
symptoms in young adult offspring: An exploration of looming cognitive style.
AB - BACKGROUND AND OBJECTIVES: Given that anxiety runs in families, it is critical to
understand the cognitive factors that may be responsible for this
intergenerational transmission. The present study offers a first step by
exploring the link between mother and father tendencies to view potentially
threatening situations as rapidly escalating toward dreaded outcomes (i.e.,
looming cognitive style) and the emotional disturbances and looming cognitive
styles of their adult offspring. METHODS: We assessed cognitive vulnerabilities,
anxiety, and depressive symptoms in a non-clinical sample (N = 382) of Italian
college students and their parents. RESULTS: The looming cognitive style of
fathers, but not mothers, was significantly related to greater anxiety in adult
offspring. This finding was obtained for both sons and daughters, and remained
even after statistically controlling for the anxiety, worry, depressive symptoms,
and anxiety sensitivity (AS) of parents). Notably, the association between
fathers' looming cognitive style and offspring symptoms was not related to their
child's depressive symptoms, and similar to prior work, served as a cognitive
marker specific to anxiety. LIMITATIONS: The present study relied on a cross
sectional design and did not use clients diagnosed with anxiety disorders.
CONCLUSIONS: The findings suggest that it may prove fruitful to consider parental
vulnerabilities such as looming cognitive styles in comprehensive cognitive and
interpersonal models of anxiety. The intergenerational transmission of emotional
difficulties seems to extend beyond anxiety to beliefs about the escalation of
threat.
PMID- 27614664
TI - In the Eye of the Illusion: Variation in Perceptual Phenomena Within an Inverted
Percept.
AB - Monocular depth cues can lead not only to illusory depth in two-dimensional
patterns but also to perspective reversals in three-dimensional objects. When a
viewer perceptually inverts (reverses) a three-dimensional object, stimuli on the
inner surfaces of that object also invert. However, the perceptual fate of
anything occurring within the space that is enclosed by the walls of a
perceptually reversible object is unknown. In the present study, perceptions of
the relative vertical heights of stimuli within a truncated pyramidal chute were
compared for stimuli placed laterally, on the inner surface of the chute, or
centrally, suspended within the volume enclosed by the chute. The typical
inversion was obtained for lateral stimuli, but central stimuli did not invert.
While central stimuli maintained their veridical vertical order, participants
experienced a considerable compression of perceptual depth. These results imply a
dilution of the illusion within the centre of the volume of space that it
encloses.
PMID- 27614665
TI - Pathology Resident Perspectives on Feedback and a Proposed Trainee Curriculum on
Giving Feedback.
AB - Objectives: Receiving and reflecting on feedback is a critical skill in medicine.
Learning how to provide effective feedback is important in assessment and
engendering performance improvement. Methods: We outline a curriculum for
laboratory medicine trainees on providing effective feedback. A group of trainees
(26/30 attendees) was surveyed regarding their perspectives on effective feedback
and impressions of an educational session focused on how to give effective
feedback. Results: The curriculum involved a 1-hour session focused on how to
provide useful feedback. The two presenters used role-plays, group discussion,
and didactic talk to present the material. Most attendees (n = 22/26) indicated
that regular or frequent effective feedback was important to their learning. When
asked, "What makes feedback effective for you?" the most frequent responses were
being specific (n = 11) and being balanced (ie, presenting both positives and
negative) (n = 10). On a Likert scale (1 = poor; 7 = excellent), attendees rated
their ability to give feedback higher after the session (mean, 5.2) vs before the
session (mean, 3.8). Conclusions: Feedback is an important component of
assessment and reflective practice. Pathology trainees believe that being
specific and balanced were characteristics of effective feedback. It is important
to provide training on giving effective feedback to pathology trainees.
PMID- 27614666
TI - Genomic Copy Number Analysis of HER2-Equivocal Breast Cancers.
AB - OBJECTIVES: Guidelines for HER2 testing define an equivocal range for HER2 using
two approved testing methods, immunohistochemistry (IHC) and in situ
hybridization (ISH). We investigated genome-wide copy number alterations in this
subgroup. METHODS: Ten breast cancers with equivocal HER2 status by both IHC and
ISH were analyzed by single-nucleotide polymorphism cytogenomic microarray (SNP
array). DNA ploidy analysis by flow cytometry was performed on nine cases with
sufficient material remaining. RESULTS: SNP array analysis showed uniform gain of
chromosome 17 (polysomy) in one case and segmental copy number gains encompassing
HER2 and the centromere in five other cases. Flow cytometry revealed
hyperdiploidy in six cases, all but one of which also had HER2 gains on SNP
array. Although there was no evidence of HER2 amplification by SNP array, six
cases showed amplification of other genomic regions, including known oncogenes in
four cases. CONCLUSIONS: A combination of hyperdiploidy and segmental copy number
gains contributes to HER2 ISH-equivocal results in most breast cancers. Cases in
which HER2 copy number gain is not corroborated by genomic analysis suggest the
presence of other contributing variables influencing ISH results. Genomic copy
number analysis also implicates non-HER2 oncogenic drivers in many cases that are
HER2 equivocal.
PMID- 27614668
TI - Hyaline Protoplasmic Astrocytopathy: A Clinicopathologic Study.
AB - OBJECTIVES: Hyaline protoplasmic astrocytopathy is a rare condition marked by the
accumulation of various proteins in the cytoplasm of protoplasmic astrocytes.
METHODS: This study retrospectively reviews the clinicopathologic features of 14
patients (nine females; mean age, 9.1 years) with hyaline protoplasmic
astrocytopathy. RESULTS: Patients had chronic seizures (mean duration, 101.1
months); mean age at seizure onset was 6.9 months. Three patients had Aicardi
syndrome, and one patient had tuberous sclerosis. Associated focal cortical
dysplasia was noted in all 14 cases. Patterns of dysplasia observed included
International League Against Epilepsy (ILAE) type I Ib (n = 7), ILAE type Ib (n =
4), ILAE type Ic (n = 2), and ILAE type IIa (n = 1). Additional pathologic
findings included evidence of contusional damage (n = 5), gray matter nodular
heterotopias (n = 3), polymicrogygria (n = 2), hemimegalencephaly (n = 2), and
hippocampal sclerosis (ILAE type II, CA1 sclerosis) (n = 1). Postoperative follow
up intervals ranged from two to 93 months (mean, 31.2 months). Seven patients
were free of seizures or had only rare disabling seizures (Engel I/II) at most
recent follow-up. Two patients had recurrent seizures with no worthwhile
improvement (Engel IV) at follow-up. CONCLUSIONS: The current series supports an
association of Aicardi syndrome (21% of cases) and focal cortical dysplasia (100%
of cases) and hyaline protoplasmic astrocytopathy.
PMID- 27614667
TI - Fine-Needle Aspiration of Epithelial-Myoepithelial Carcinoma of the Parotid Gland
With Prominent Adenoid Cystic Carcinoma-Like Cribriform Features: Avoiding a
Diagnostic Pitfall.
AB - OBJECTIVES: Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland
malignancy associated with an overall good prognosis. Fine-needle aspiration
(FNA) typically shows a dual population of myoepithelial and ductal cells.
Rarely, acellular matrix globules are present, raising a differential diagnosis
of adenoid cystic carcinoma (AdCC), a more aggressive salivary gland malignancy
associated with a poor long-term prognosis. We report an FNA case of EMC
containing a predominant pattern of AdCC-like spherical globules. METHODS: We
compare features of an unusual case of EMC with those of cribriform AdCC to
arrive at morphologic clues to the correct diagnosis. RESULTS: Distinguishing
features of EMC on FNA include (1) a prominent population of myoepithelial cells
vs the predominance of basaloid cells in AdCC and (2) cohesive matrix globules
with a peripheral rim of pale-staining basement membrane material compared with
the dyscohesive matrix globules of AdCC. Immunochemical markers (S100, CD117, and
MyB) are also useful. CONCLUSIONS: Although EMC and AdCC can both contain
spherical matrix globules, close evaluation of the cytomorphology of the globules
and their relationship to surrounding cells provides a clue to distinguish the
two neoplasms.
PMID- 27614669
TI - Correction and Letter to Editor based on the article "An evaluation of the
functional and radiological results of percutaneous vertebroplasty versus
conservative treatment for acute symptomatic osteoporotic spinal fractures".
PMID- 27614670
TI - Authors' reply: A new technique to close open abdomen using negative pressure
therapy and elastic gums.
PMID- 27614671
TI - Impact of olecranon fracture malunion: Study on the importance of PUDA (Proximal
Ulna Dorsal Angulation).
AB - PURPOSE: The Proximal Ulna Dorsal Angulation (PUDA) is part of the proximal
ulna's normal anatomy. The importance of restoring ulnar anatomy characteristics
precisely after olecranon fracture is not known, however, failure to recreate the
PUDA after surgery may result in poorer functional outcomes. The purpose of this
study is to evaluate the impact of minimal proximal ulna malunion on elbow ROM
and function at least one year after olecranon ORIF. METHOD: A retrospective
comparative cohort study took place in three level-1 trauma centers. Forty-nine
adult volunteers who underwent ORIF for olecranon fracture were included.
Patients were separated into two groups according to PUDA malreduction-defined as
more than 5 degrees of difference between the fractured and the contralateral
elbow. OUTCOME MEASUREMENTS: Radiographic ROM measurement, demographic data and
quality of life questionnaires were recorded (PREE, MEPS, Q-DASH, SF12, VAS).
RESULTS: The mean follow up was 3 years and 9 months (1-7 years). There was no
difference in terms of outcome, quality of reduction or range of motion between
patients treated with plate or tension band. The mean PUDA on the fracture side
was different from the normal side (2.20 vs 4.90, p<0.001). Fourteen patients
(29%) had PUDA malunion. Those patients had decreased elbow flexion (-7 degrees ,
p=0.011), extension (-11.2 degrees , p=0.013) and total ROM (-18.6 degrees ,
p=0.006) as opposed to the control group. Both groups had comparable quality of
life questionnaire scores. Alcohol consumption was the only risk factor
associated with worse scores. CONCLUSION: Incidence of olecranon malunion-as
defined by PUDA measurement - was 29% and it was associated with decreased elbow
range of motion. Alcohol consumption was correlated with a worse prognosis in our
series of patients. Tension band and plate fixation can maintain a good reduction
in terms of PUDA and the choice of fixation method does not influence outcome.
LEVEL OF EVIDENCE: III Therapeutic study.
PMID- 27614672
TI - Hotspots and causes of motor vehicle crashes in Baltimore, Maryland: A geospatial
analysis of five years of police crash and census data.
AB - INTRODUCTION: Road traffic injuries are a leading killer of youth (aged 15-29)
and are projected to be the 7th leading cause of death by 2030. To better
understand road traffic crash locations and characteristics in the city of
Baltimore, we used police and census data, to describe the epidemiology,
hotspots, and modifiable risk factors involved to guide further interventions.
MATERIALS AND METHODS: Data on all crashes in Baltimore City from 2009 to 2013
were made available from the Maryland Automated Accident Reporting System.
Socioeconomic data collected by the US CENSUS 2010 were obtained. A time series
analysis was conducted using an ARIMA model. We analyzed the geographical
distribution of traffic crashes and hotspots using exploratory spatial data
analysis and spatial autocorrelation. Spatial regression was performed to
evaluate the impact of socioeconomic indicators on hotspots. RESULTS: In
Baltimore City, between 2009 and 2013, there were a total of 100,110 crashes
reported, with 1% of crashes considered severe. Of all crashes, 7% involved
vulnerable road users and 12% had elderly or youth involvement. Reasons for
crashes included: distracted driving (31%), speeding (6%), and alcohol or drug
use (5%). After 2010, we observed an increasing trend in all crashes especially
from March to June. Distracted driving then youth and elderly drivers were
consistently the highest risk factors over time. Multivariate spatial regression
model including socioeconomic indicators and controlling for age, gender and
population size did not show a distinct predictor of crashes explaining only 20%
of the road crash variability, indicating crashes are not geographically
explained by socioeconomic indicators alone. CONCLUSION: In Baltimore City, road
traffic crashes occurred predominantly in the high density center of the city,
involved distracted driving and extremes of age with an increase in crashes from
March to June. There was no association between socioeconomic variables where
crashes occurred and hotspots. In depth analysis of how modifiable risk factors
are impacted by geospatial characteristics and the built environment is warranted
in Baltimore to tailor interventions.
PMID- 27614673
TI - Head injury assessment of non-lethal projectile impacts: A combined
experimental/computational method.
AB - The main objective of this study is to develop a methodology to assess this risk
based on experimental tests versus numerical predictive head injury simulations.
A total of 16 non-lethal projectiles (NLP) impacts were conducted with rigid
force plate at three different ranges of impact velocity (120, 72 and 55m/s) and
the force/deformation-time data were used for the validation of finite element
(FE) NLP. A good accordance between experimental and simulation data were
obtained during validation of FE NLP with high correlation value (>0.98) and peak
force discrepancy of less than 3%. A state-of-the art finite element head model
with enhanced brain and skull material laws and specific head injury criteria was
used for numerical computation of NLP impacts. Frontal and lateral FE NLP impacts
to the head model at different velocities were performed under LS-DYNA. It is the
very first time that the lethality of NLP is assessed by axonal strain
computation to predict diffuse axonal injury (DAI) in NLP impacts to head. In
case of temporo-parietal impact the min-max risk of DAI is 0-86%. With a velocity
above 99.2m/s there is greater than 50% risk of DAI for temporo-parietal impacts.
All the medium- and high-velocity impacts are susceptible to skull fracture, with
a percentage risk higher than 90%. This study provides tool for a realistic
injury (DAI and skull fracture) assessment during NLP impacts to the human head.
PMID- 27614674
TI - Cardiac rehabilitation in the acute care setting: Integrative review.
AB - BACKGROUND: Phase one cardiac rehabilitation (CR) is an essential component of
care for patients with coronary heart disease. With optimal program delivery,
health outcomes can be improved. OBJECTIVES: To conduct an integrative review
that explores Phase one CR for patients hospitalised with coronary heart disease.
DESIGN: Integrative literature review (2003-2014) Data sources: The literature
search included Medline, Cumulative Index to Nursing and Allied Health Literature
(CINAHL), Experta Medica Database (EMBASE), Psycinfo, Clinical Practice
Guidelines Portal, Cochrane Library, Clinical Evidence (BMJ) and Google Scholar.
REVIEW METHODS: The Joanna Briggs Institute critical appraisal tools relevant to
study methodology were utilised. Studies included for review were peer reviewed,
published in English. Studies included Phase one CR intervention/s or the
provision of education to patients diagnosed with coronary heart disease in the
acute care setting prior to hospital discharge. RESULTS: In the past decade
cardiac researchers have predominantly focused on patients and health
professionals perceptions, CR interventions, and patient education. Factors that
impede delivery of Phase one CR, such as time, workload etc. were also reported.
CONCLUSIONS: The implementation of Phase one CR delivery requires optimisation to
enable patients with coronary heart disease to achieve positive health outcomes
post hospitalisation. Future interventions should address the factors that impede
delivery of Phase one CR.
PMID- 27614675
TI - n-3 fatty acid-based parenteral nutrition improves postoperative recovery for
cirrhotic patients with liver cancer: A randomized controlled clinical trial.
AB - BACKGROUND & AIMS: A new lipid emulsion enriched in n-3 fatty acid has been
reported to prevent hepatic inflammation in patients following major surgery.
However, the role of n-3 fatty acid-based parenteral nutrition for postoperative
patients with cirrhosis-related liver cancer is unclear. We investigated the
safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic
patients with liver cancer followed hepatectomy. METHODS: A prospective
randomized controlled clinical trial (Registered under ClinicalTrials.gov
Identifier no. NCT02321202) was conducted for cirrhotic patients with liver
cancer that underwent hepatectomy between March 2010 and September 2013 in our
institution. We compared isonitrogenous total parenteral nutrition with 20%
Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany)
(treatment group) to Structolipid alone (control group) for five days
postoperatively, in the absence of enteral nutrition. RESULTS: We enrolled 320
patients, and 312 (97.5%) were included in analysis (155 in the control group and
157 in the treatment group). There was a significant reduction of morbidity and
mortality in the treatment group, when compared with the control group (total
complications 78 [50.32%] vs. 46 [29.30%]; P < 0.001, total infective
complications, 30 [19.35%] vs. 15 [9.55%]; P = 0.014), overall mortality (5
[3.23%] vs. 1 [0.64%]; P = 0.210), and hospital stay (12.56 +/- 3.21 d vs. 10.17
+/- 3.15 d; P = 0.018). CONCLUSIONS: We found that addition of n-3 fatty acid
based parenteral nutrition significantly improved postoperative recovery for
cirrhotic patients with liver cancer following hepatectomy, with a significant
reduction in overall mortality and length of hospital stay.
PMID- 27614676
TI - Placental weight in pregnancies with high or low hemoglobin concentrations.
AB - OBJECTIVES: To study the associations of maternal hemoglobin concentrations with
placental weight and placental to birthweight ratio. STUDY DESIGN: In this
retrospective cohort study, we included all singleton pregnancies during the
years 1998-2013 at a large public hospital in Norway (n=57062). We compared mean
placental weight and placental to birthweight ratio according to maternal
hemoglobin concentrations: <9g/dl, 9-13.5g/dl or >13.5g/dl. The associations of
maternal hemoglobin concentrations with placental weight and placental to
birthweight ratio were estimated by linear regression analyses, and adjustments
were made for gestational age at birth, preeclampsia, parity, maternal age,
diabetes, body mass index, smoking, offspring sex and year of birth. RESULTS: In
pregnancies with maternal hemoglobin concentrations <9g/dl, mean placental weight
was 701.2g (SD 160.6g), followed by 678.1g (SD 150.2g) for hemoglobin
concentrations 9-13.5g/dl and 655.5g (SD 147.7g) for hemoglobin concentrations
>13.5g/dl (ANOVA, p<0.001). Mean placental to birthweight ratio was highest in
pregnancies with maternal hemoglobin concentrations <9g/dl (0.203 (SD 0.036)). We
found no difference in mean placental to birthweight ratio for maternal
hemoglobin concentrations 9-13.5g/dl (0.193 (SD 0.040)) and >13.5g/dl (0.193 (SD
0.043)). Adjustments for our study factors did not alter the estimates notably.
CONCLUSIONS: Placental weight decreased with increasing maternal hemoglobin
concentrations. The high placental to birthweight ratio with low maternal
hemoglobin concentrations suggests differences in placental growth relative to
fetal growth across maternal hemoglobin concentrations.
PMID- 27614677
TI - A multistage selective weighting method for improved microwave breast tomography.
AB - Microwave tomography has shown potential to successfully reconstruct the
dielectric properties of the human breast, thereby providing an alternative to
other imaging modalities used in breast imaging applications. Considering the
costly forward solution and complex iterative algorithms, computational
complexity becomes a major bottleneck in practical applications of microwave
tomography. In addition, the natural tendency of microwave inversion algorithms
to reward high contrast breast tissue boundaries, such as the skin-adipose
interface, usually leads to a very slow reconstruction of the internal tissue
structure of human breast. This paper presents a multistage selective weighting
method to improve the reconstruction quality of breast dielectric properties and
minimize the computational cost of microwave breast tomography. In the proposed
two stage approach, the skin layer is approximated using scaled microwave
measurements in the first pass of the inversion algorithm; a numerical skin model
is then constructed based on the estimated skin layer and the assumed dielectric
properties of the skin tissue. In the second stage of the algorithm, the skin
model is used as a priori information to reconstruct the internal tissue
structure of the breast using a set of temporal scaling functions. The proposed
method is evaluated on anatomically accurate MRI-derived breast phantoms and a
comparison with the standard single-stage technique is presented.
PMID- 27614678
TI - Automated layer segmentation of macular OCT images via graph-based SLIC
superpixels and manifold ranking approach.
AB - Using the graph-based a simple linear iterative clustering (SLIC) superpixels and
manifold ranking technology, a novel automated intra-retinal layer segmentation
method is proposed in this paper. Eleven boundaries of ten retinal layers in
optical coherence tomography (OCT) images are exactly, fast and reliably
quantified. Instead of considering the intensity or gradient features of the
single-pixel in most existing segmentation methods, the proposed method focuses
on the superpixels and the connected components-based image cues. The image is
represented as some weighted graphs with superpixels or connected components as
nodes. Each node is ranked with the gradient and spatial distance cues via graph
based Dijkstra's method or manifold ranking. So that it can effectively overcome
speckle noise, organic texture and blood vessel artifacts issues. Segmentation is
carried out in a three-stage scheme to extract eleven boundaries efficiently. The
segmentation algorithm is validated on 2D and 3D OCT images in three databases,
and is compared with the manual tracings of two independent observers. It
demonstrates promising results in term of the mean unsigned boundaries errors,
the mean signed boundaries errors, and layers thickness errors.
PMID- 27614679
TI - Work-related asthma secondary to IgE-mediated reactions to rodents successfully
treated with immunotherapy.
PMID- 27614680
TI - Preoperative image-guided brachytherapy in early stage cervical cancers.
AB - OBJECTIVE: To examine the clinical results of a preoperative image-guided pulse
dose-rate brachytherapy (PDR-BT) in early stage cervical cancer.
MATERIALS/METHODS: We examined the outcome of consecutive patients with early
stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004
and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The
objective was to deliver 60Gy to 100% of the intermediate risk clinical target
volume. Brachytherapy was followed, 6-8weeks later, by a radical
hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/- para-aortic lymph
node dissection. Patients with positive lymph nodes had postoperative
chemoradiation. RESULTS: 77 patients met the above criteria of preoperative PDR
BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological
response. Four (5.2%) had a tumour residuum?1cm. Median follow-up was 46.8months.
5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was
observed. The presence of lymph nodal metastases, a tumour size>3cm and a
brachytherapy/surgery time interval?9weeks correlated with a poorer DFS. Six
postoperative complications were encountered (7.8%). Total reference air kerma
correlated with late vaginal toxicity (p=0.02). CONCLUSIONS: A preoperative image
guided PDR-BT was safe and effective. Predictive factors for survival and
toxicity were evidenced.
PMID- 27614681
TI - Multivariable normal tissue complication probability model-based treatment plan
optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck
radiotherapy.
AB - BACKGROUND AND PURPOSE: Radiotherapy of the head and neck is challenged by the
relatively large number of organs-at-risk close to the tumor. Biologically
oriented objective functions (OF) could optimally distribute the dose among the
organs-at-risk. We aimed to explore OFs based on multivariable normal tissue
complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube
feeding dependence (TFD). MATERIALS AND METHODS: One hundred head and neck cancer
patients were studied. Additional to the clinical plan, two more plans (an OFDYS
and OFTFD-plan) were optimized per patient. The NTCP models included up to four
dose-volume parameters and other non-dosimetric factors. A fully automatic plan
optimization framework was used to optimize the OFNTCP-based plans. RESULTS: All
OFNTCP-based plans were reviewed and classified as clinically acceptable. On
average, the Deltadose and DeltaNTCP were small comparing the OFDYS-plan, OFTFD
plan, and clinical plan. For 5% of patients NTCPTFD reduced >5% using OFTFD-based
planning compared to the OFDYS-plans. CONCLUSIONS: Plan optimization using
NTCPDYS- and NTCPTFD-based objective functions resulted in clinically acceptable
plans. For patients with considerable risk factors of TFD, the OFTFD steered the
optimizer to dose distributions which directly led to slightly lower predicted
NTCPTFD values as compared to the other studied plans.
PMID- 27614682
TI - A rapid and highly sensitive immunoassay format for human lipocalin-2 using
multiwalled carbon nanotubes.
AB - A sensitive and rapid sandwich immunoassay (IA) was developed for human lipocalin
2 (LCN2) by functionalizing a KOH-treated polystyrene microtiter plate with
multiwalled carbon nanotubes (MWCNTs) dispersed in 3-aminoproyltriethoxysilane
(APTES). The significantly increased surface area due to the presence of MWCNTs
led to a high immobilization density of 1-ethyl-3-(3-dimethylaminopropyl)
carbodiimide (EDC) activated anti-LCN2 capture antibodies (Ab). The anti-LCN2 Ab
bound MTPs were stable for 6 weeks when stored in 0.1M PBS, pH 7.4 at 4 degrees
C. The IA detects LCN2 from 0.6 to 5120pgmL-1 with a limit of detection (LOD) and
limit of quantification (LOQ) of 0.9pgmL-1 and 6pgmL-1, respectively. The assay
offered a ~50-fold lower LOD and ~3-fold faster IA, compared to a commercial
sandwich enzyme-linked immunosorbent assay kit.
PMID- 27614683
TI - A fluorescence turn-on biosensor based on graphene quantum dots (GQDs) and
molybdenum disulfide (MoS2) nanosheets for epithelial cell adhesion molecule
(EpCAM) detection.
AB - This paper presents a "turn-on" fluorescence biosensor based on graphene quantum
dots (GQDs) and molybdenum disulfide (MoS2) nanosheets for rapid and sensitive
detection of epithelial cell adhesion molecule (EpCAM). PEGylated GQDs were used
as donor molecules, which could not only largely increase emission intensity but
also prevent non-specific adsorption of PEGylated GQD on MoS2 surface. The
sensing platform was realized by adsorption of PEGylated GQD labelled EpCAM
aptamer onto MoS2 surface via van der Waals force. The fluorescence signal of GQD
was then quenched by MoS2 nanosheets via fluorescence resonance energy transfer
(FRET) mechanism. In the presence of EpCAM protein, the stronger specific
affinity interaction between aptamer and EpCAM protein could detach GQD labelled
EpCAM aptamer from MoS2 nanosheets, leading to the restoration of fluorescence
intensity. By monitoring the change of fluorescence signal, the target EpCAM
protein could be detected sensitively and selectively with a linear detection
range from 3nM to 54nM and limit of detection (LOD) around 450pM. In addition,
this nanobiosensor has been successfully used for EpCAM-expressed breast cancer
MCF-7 cell detection.
PMID- 27614684
TI - Ambient light-based optical biosensing platform with smartphone-embedded
illumination sensor.
AB - We present a hand-held optical biosensing system utilizing a smartphone-embedded
illumination sensor that is integrated with immunoblotting assay method. The
smartphone-embedded illumination sensor is regarded as an alternative optical
receiver that can replaces the conventional optical analysis apparatus because
the illumination sensor can respond to the ambient light in a wide range of
wavelengths, including visible and infrared. To demonstrate the biosensing
applicability of our system employing the enzyme-mediated immunoblotting and
accompanying light interference, various types of ambient light conditions
including outdoor sunlight and indoor fluorescent were tested. For the
immunoblotting assay, the biosensing channel generating insoluble precipitates as
an end product of the enzymatic reaction is fabricated and mounted on the
illumination sensor of the smartphone. The intensity of penetrating light arrives
on the illumination sensor is inversely proportional to the amount of
precipitates produced in the channel, and these changes are immediately analyzed
and quantified via smartphone software. In this study, urinary C-terminal
telopeptide fragment of type II collagen (uCTX-II), a biomarker of osteoarthritis
diagnosis, was tested as a model analyte. The developed smartphone-based sensing
system efficiently measured uCTX-II in the 0-5ng/mL concentration range with a
high sensitivity and accuracy under various light conditions. These assay results
show that the illumination sensor-based optical biosensor is suitable for point
of-care testing (POCT).
PMID- 27614686
TI - Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is
expected to be a potential therapeutic target.
AB - This study investigated the significance of La-related protein 1 (LARP1) in the
development and progression of colorectal cancer (CRC). Quantitative real-time
polymerase chain reaction and Western blot analyses were carried out to determine
the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent
normal mucosa. The expression of LARP1 was upregulated in CRC.
Immunohistochemical analysis using tissue microarray was performed. A positive
correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the
area of proliferation was observed using the Spearman's correlation coefficient
test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly
correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001),
American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank
(P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of
LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting
Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed
that LARP1 was an independent prognostic factor for overall survival (OS; hazard
rate (HR) = 0.244; 95 % confidence interval (CI), 0.078-0.769; P = 0.016) and
disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086-0.917; P = 0.035) in CRC
patients. LARP1 plays an important role in the proliferation of colorectal cancer
and represents a new prognostic indicator.
PMID- 27614688
TI - The Athletic Body.
AB - This paper seeks to explore the attraction and the beauty of the contemporary
athletic body. It will be suggested that a body shaped through muscular bulk and
definition has come to be seen as aesthetically normative. This body differs from
the body of athletes from the early and mid-twentieth century. It will be argued
that the contemporary body is not merely the result of advances in sports
science, but rather that it is expressive of certain meanings and values. The
visual similarity of the contemporary athletic body and that of the comic book
superhero suggests that both bodies carry a similar potential for narrative story
telling, and that their attraction is bound up with this narrative potential. The
superhero and athlete live meaningful lives, pursuing clear and morally
unambiguous goals. The aesthetic attraction of the body lies in its capacity to
facilitate the articulation of a story of a meaningful life, and to do so in the
face of the growing anomie and thus meaninglessness of life as experienced in
contemporary society. Athleticism offers an illusion of meaning, serving to
reproduce dominant justificatory narratives and social stereotypes. Yet, as an
illusion of meaning, it may be challenged and negotiated, not least with respect
to its bias towards a certain form of the male body. The female athletic body
disrupts the illusion, opening up new existential possibilities, new ways of
living and being, and thus new, and potentially disruptive, narratives.
PMID- 27614690
TI - Academy of Nutrition and Dietetics Methodology for Developing Evidence-Based
Nutrition Practice Guidelines.
PMID- 27614685
TI - Role of angiogenic factors of herbal origin in regulation of molecular pathways
that control tumor angiogenesis.
AB - The formation of blood capillaries to sustain development and growth of new
tissues is referred to as angiogenesis. Angiogenesis is pivotal in both
carcinogenesis and metastasis since capillaries are the sole source of supplying
nutrients and oxygen to the proliferating tumor cells; therefore, this dependency
of tumor growth on angiogenesis challenges researchers to halt tumor growth by
targeting angiogenesis with the help of either synthetic or natural inhibitors.
Many synthetic inhibitors of angiogenesis have not only come into force but also
resulted in some severe adverse effects. Natural compounds may effectively fit
into this condition and possibly decrease the time of treatment. In the recent
past, literature is replete with evidences advocating the usefulness of natural
compounds that target multiple biochemical pathways. The additional advantage of
natural compounds is that their active principles interact with one another and
work synergistically to give more meaningful and reliable effects than individual
principle. Hence, if we are somehow able to combine more than two natural
compounds, then it may be possible to enhance their potential by many folds,
which shall prove to be very effective in combating tumor angiogenesis. This
review shall discuss the concept of angiogenesis, molecular pathways, and
angiogenic inhibitors and their specific targets and potential of natural
compounds to greatly enhance the current knowledge of angiogenesis-inhibiting
factors.
PMID- 27614689
TI - Maternal Strategies to Access Food Differ by Food Security Status.
AB - BACKGROUND: Household food insecurity is associated with health and behavior
risk. Much less is known about how food insecurity is related to strategies that
adults use in accessing food: how and where they shop, use of alternative food
sources, and their ability to manage resources. OBJECTIVE: To examine how
maternal behaviors, including shopping, accessing alternative sources of food,
and managing resources, are related to household food security status (HHFSS).
DESIGN: Cross-sectional study collecting survey data on HHFSS, shopping
behaviors, use of alternative food sources, and managing resources obtained from
low-income mothers of preschool-aged children. PARTICIPANTS: One hundred sixty
four low-income mothers of young children (55% Hispanic) from two communities in
Rhode Island. MEASURES: HHFSS was measured using 10 items from the 18-item Core
Food Security Module to assess adult food security. Mothers were surveyed about
where, when, and how often they shopped; the strategies they use when shopping;
their use of alternative sources of food, including federal, state, and local
assistance; and their ability to manage their resources. STATISTICAL ANALYSIS:
Analysis of variance and chi2 analyses assessed the associations between
demographic variables, shopping, accessing alternative food sources, and managing
resources, and HHFSS. Multivariate logistic regression assessed the associations
between HHFSS and maternal demographic variables, food shopping, strategies,
alternative sources of food, and ability to manage resources. RESULTS: Maternal
age and language spoken at home were significantly associated with HHFSS; food
insecurity was 10% more likely among older mothers (adjusted odds ratio [aOR]
1.10, 95% CI 1.03 to 1.17) and 2.5 times more likely among Spanish-speaking
households (compared with non-Spanish speaking [aOR 3.57, 95% CI 1.25 to 10.18]).
Food insecurity was more likely among mothers reporting more informal strategies
(aOR 1.98, 95% CI 1.28 to 3.01; P<0.05) and perceiving greater inability to
manage resources (aOR 1.60, 95% CI 1.30 to 1.98; P<0.05). CONCLUSIONS: The
results suggest that low-income mothers use a variety of strategies to feed their
families and that the strategies they use vary by HHFSS. Community nutrition
programs and providers will need to consider these strategies when counseling
families at risk for food insecurity and provide guidance to minimize the
influence on healthy food choices.
PMID- 27614687
TI - NETs in cancer.
AB - Many aspects of neutrophil hyperactivity and its role in numerous immune
responses still remain a mystery. A new neutrophil mechanism was discovered
recently, i.e., the formation of neutrophil extracellular traps (NETs). These
structures, composed of DNA strands and neutrophil granule proteins, are an
element of the non-specific immune response and bind pathogens to prevent their
spread and ensure increased local concentrations of toxic factors. Research on
this phenomenon shows that tumor-associated neutrophils (TANs) also form and
release NETs. Reports on the role of NETs in the course of cancer are scarce, and
the opinions on the involvement of extracellular traps in the disease are
divided, indicating a dual function. There is speculation about the anti-cancer
properties of NETs connected with direct killing of cancer cells or stimulation
of the immune system. On the other hand, the trap structures might promote
migration and immune escape of cancer cells or constitute a physical barrier
between cancer cells and immune-competent cells. This article summarizes our
knowledge about the proven roles of NETs in the course of cancer with particular
focus on the significance of NETs as prognosis biomarkers in the course of the
neoplastic process and their potential use in therapy.
PMID- 27614691
TI - A potential concomitance of papillary fibroelastoma in the case with cardiac
myxoma.
AB - An 84-year-old woman was referred to our hospital with a suspected cardiac tumor
detected by transthoracic echocardiography performed as a preoperative
examination of gastric cancer. In addition to a tumor in the left atrium, we
found on cardiac ultrasound a 15-mm mobile tumor that adhered to the aortic
valve. Gross findings and histological examination confirmed that the tumor in
the left atrium was a cardiac myxoma, and that the tumor adhered to the aortic
valve was a papillary fibroelastoma. We experienced a rare case where
preoperative examination before gastrectomy accidentally revealed concomitant
cardiac tumors.
PMID- 27614692
TI - Biomimetic Salmonella: A Next-Generation Therapeutic Vector?
AB - Designing bacterial vectors for cancer therapy represents a major challenge.
Recent studies have explored novel strategies to balance benefit and safety. A
study by Mercado-Lubo et al. has developed a next-generation concept combining
bacterial properties with nanoparticles, demonstrating efficacy in combination
with chemotherapeutics.
PMID- 27614693
TI - Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal
Tumors: A Systematic Review and Meta-analysis of Comparative Studies.
AB - BACKGROUND: Partial nephrectomy (PN) is the reference standard of management for
a cT1a renal mass. However, its role in the management of larger tumors (cT1b and
cT2) is still under scrutiny. OBJECTIVE: To conduct a meta-analysis assessing
functional, oncologic, and perioperative outcomes of PN and radical nephrectomy
(RN) in the specific case of larger renal tumors (>=cT1b). The primary endpoint
was an overall analysis of cT1b and cT2 masses. The secondary endpoint was a
sensitivity analysis for cT2 only. EVIDENCE ACQUISITION: A systematic literature
review was performed up to December 2015 using multiple search engines to
identify eligible comparative studies. A formal meta-analysis was performed for
studies comparing PN to RN for both cT1b and cT2 tumors. In addition, a
sensitivity analysis including the subgroup of studies comparing PN to RN for cT2
only was conducted. Pooled estimates were calculated using a fixed-effects model
if no significant heterogeneity was identified; alternatively, a random-effects
model was used when significant heterogeneity was detected. For continuous
outcomes, the weighted mean difference (WMD) was used as summary measure. For
binary variables, the odds ratio (OR) or risk ratio (RR) was calculated with 95%
confidence interval (CI). Statistical analyses were performed using Review
Manager 5 (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS: Overall, 21
case-control studies including 11204 patients (RN 8620; PN 2584) were deemed
eligible and included in the analysis. Patients undergoing PN were younger (WMD
2.3 yr; p<0.001) and had smaller masses (WMD -0.65cm; p<0.001). Lower estimated
blood loss was found for RN (WMD 102.6ml; p<0.001). There was a higher likelihood
of postoperative complications for PN (RR 1.74, 95% CI 1.34-2.2; p<0.001).
Pathology revealed a higher rate of malignant histology for the RN group (RR
0.97; p=0.02). PN was associated with better postoperative renal function, as
shown by higher postoperative estimated glomerular filtration rate (eGFR; WMD
12.4ml/min; p<0.001), lower likelihood of postoperative onset of chronic kidney
disease (RR 0.36; p<0.001), and lower decline in eGFR (WMD -8.6ml/min; p<0.001).
The PN group had a lower likelihood of tumor recurrence (OR 0.6; p<0.001), cancer
specific mortality (OR 0.58; p=0.001), and all-cause mortality (OR 0.67;
p=0.005). Four studies compared PN (n=212) to RN (n=1792) in the specific case of
T2 tumors (>7cm). In this subset of patients, the estimated blood loss was higher
for PN (WMD 107.6ml; p<0.001), as was the likelihood of complications (RR 2.0;
p<0.001). Both the recurrence rate (RR 0.61; p=0.004) and cancer-specific
mortality (RR 0.65; p=0.03) were lower for PN. CONCLUSIONS: PN is a viable
treatment option for larger renal tumors, as it offers acceptable surgical
morbidity, equivalent cancer control, and better preservation of renal function,
with potential for better long-term survival. For T2 tumors, PN use should be
more selective, and specific patient and tumor factors should be considered.
Further investigation, ideally in a prospective randomized fashion, is warranted
to better define the role of PN in this challenging clinical scenario. PATIENT
SUMMARY: We performed a cumulative analysis of the literature to determine the
best treatment option in cases of localized kidney tumor of higher clinical stage
(T1b and T2, as based on preoperative imaging). Our findings suggest that
removing only the tumor and saving the kidney might be an effective treatment
modality in terms of cancer control, with the advantage of preserving the kidney
function. However, a higher risk of perioperative complications should be taken
into account when facing larger tumors (clinical stage T2) with kidney-sparing
surgery.
PMID- 27614694
TI - Personalise Medicine, Do Not Medicalise Persons: The Case of Patients with Stage
I Testis Tumour Undergoing Surveillance.
PMID- 27614695
TI - Primum Non Nocere: Critically Assessing the Morbidity of Prostate Biopsy.
PMID- 27614697
TI - Analysis of cornea curvature using radial basis functions - Part I: Methodology.
AB - We discuss the solution of cornea curvature using a meshless method based on
radial basis functions (RBFs). A full two-dimensional nonlinear thin membrane
partial differential equation (PDE) model is introduced and solved using the
multiquadratic (MQ) and inverse multiquadratic (IMQ) RBFs. This new approach does
not rely on radial symmetry or other simplifying assumptions in respect of the
cornea shape. It also provides an alternative to corneal topography modeling
methods requiring accurate material parameter values, such as Young's modulus and
Poisson ratio, that may not be available. The results show good agreement with
published corneal data and allow back calculations for estimating certain
physical properties of the cornea, such as tension and elasticity coefficient.
All calculations and generation of graphics were performed using the R language
programming environment [34] and RStudio, the integrated development environment
(IDE) for R [36], both of which are open source and free to download. Part II
[48] of this paper demonstrates how the method has been used to provide a very
accurate fit to a corneal measured data set.
PMID- 27614696
TI - In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous
recombination deficient and proficient ovarian carcinoma.
AB - OBJECTIVE: Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging
responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal
treatment setting remains unknown. We assessed the effect of niraparib on HGSOC
patient-derived xenograft (PDX) models as well as the relationship between
certain markers of homologous recombination (HR) status, including BRCA1/2
mutations and formation of RAD51 foci after DNA damage, and response of these
PDXs to niraparib in vivo. METHODS: Massively parallel sequencing was performed
on HGSOCs to identify mutations contributing to HR deficiency. HR pathway
integrity was assessed using fluorescence microscopy-based RAD51 focus formation
assays. Effects of niraparib (MK-4827) on treatment-naive PDX tumor growth as
monotherapy, in combination with carboplatin/paclitaxel, and as maintenance
therapy were assessed by transabdominal ultrasound. Niraparib responses were
correlated with changes in levels of poly(ADP-ribose), PARP1, and repair proteins
by western blotting. RESULTS: Five PDX models were evaluated in vivo. Tumor
regressions were induced by single-agent niraparib in one of two PDX models with
deleterious BRCA2 mutations and in a PDX with RAD51C promoter methylation.
Diminished formation of RAD51 foci failed to predict response, but Artemis loss
was associated with resistance. Niraparib generally failed to enhance responses
to carboplatin/paclitaxel chemotherapy, but maintenance niraparib therapy delayed
progression in a BRCA2-deficient PDX. CONCLUSIONS: Mutations in HR genes are
neither necessary nor sufficient to predict response to niraparib. Assessment of
repair status through multiple complementary assays is needed to guide PARP
inhibitor therapy, design future clinical trials and identify ovarian cancer
patients most likely to benefit from PARP inhibition.
PMID- 27614699
TI - Ambulatory patients with spina bifida are 50% more likely to be fecally continent
than non-ambulatory patients, particularly after a MACE procedure.
AB - INTRODUCTION: While fecal incontinence (FI) affects many patients with spina
bifida (SB), it is unclear if it is associated with ambulatory status. OBJECTIVE:
To determine if ambulatory status is associated with FI, and a potential
confounding variable, in patients with and without a Malone antegrade continence
enema (MACE). STUDY DESIGN: This study retrospectively reviewed of patients aged
>=8 years with SB who were enrolled in an international quality of life study at
outpatient visits (January 2013 to September 2015). Patients reported FI over the
last 4 weeks (strict criteria: any FI/accidents vs no FI). Patients unable to
self-report FI due to developmental delay were excluded. Those who were
ambulating outdoors with/without braces/crutches were considered community
ambulators. Non-parametric tests and logistic regression were used for analysis.
RESULTS: A total of 115 patients with a MACE and 57 without a MACE were similar
in gender (P = 0.99), ventriculoperitoneal status (P = 0.15) and age (16.0 vs
15.4 years, P = 0.11). Median ages at MACE procedure and follow-up were 7.0 and
8.2 years, respectively, and all used the MACE >=3x/week. They were less likely
to be ambulators (54.8 vs 71.9%, P = 0.03). In patients with a MACE, 64 (55.7%)
had total fecal continence, compared with 29 (50.9%) without a MACE (P = 0.62).
In the MACE group, ambulators were more likely to be continent compared with non
ambulatory patients (65.1 vs 44.2%, P = 0.04) (Table). Although not statistically
significant, a similar difference was observed in the non-MACE group (56.1 vs
37.5%, P = 0.25). In the MACE group, continent and incontinent patients,
regardless of ambulatory status, had similar rates of MACE use, additive use and
time for MACE completion (P >= 0.43). MACE ambulators were more likely to be
continent than MACE non-ambulators on multivariate analysis (OR 3.26, P = 0.01).
DISCUSSION: This study reported higher than typical FI rates since: (1) it used a
stringent definition of total fecal continence; (2) patients without FI were
perhaps less likely to participate; and (3) it relied on patient-reported rather
than clinician-reported outcomes. This cross-sectional study should not be
interpreted as "MACE procedure is ineffective;" this would require a longitudinal
study. The present findings may not apply to young children or those with
significant developmental delay (patients excluded from the study). CONCLUSIONS:
Ambulatory patients with SB are 50% more likely to have total fecal continence on
long-term follow-up, particularly after a MACE procedure. Ambulatory status is a
significant confounder of FI and should be considered in future analyses.
PMID- 27614698
TI - Laparoscopic pyeloplasty versus open pyeloplasty for recurrent ureteropelvic
junction obstruction in children.
AB - INTRODUCTION AND OBJECTIVES: Recurrent ureteropelvic junction obstruction (UPJO)
in children is an operative challenge. Minimally invasive endourological
treatment options for secondary UPJO have suboptimal success rates; hence, there
is a re-emergence of interest about redo pyeloplasty. The present study presented
experience with laparoscopic management of previously failed pyeloplasty compared
with open redo pyeloplasty in children. STUDY DESIGN: Twenty-four children with
recurrent UPJO who underwent transperitoneal dismembered laparoscopic pyeloplasty
were studied. Operative, postoperative, and follow-up functional details were
recorded and compared with those of open pyeloplasty (n = 15) carried out for
recurrent UPJO by the same surgeon during the same study period. RESULTS:
Demographic data were comparable in the laparoscopic and open groups, except for
a significantly lower GFR in the open group (24.8 vs 38.2 ml/min, P = 0.0001).
Mean time to failure of the original repair was 20.2 months (23.6 months for redo
laparoscopic pyeloplasty, 18.8 months for redo open). The success rate of
laparoscopic redo pyeloplasty was 91.7 vs 100% in open redo pyeloplasty. Compared
with redo open pyeloplasty, the mean operative time was longer (211.4 +/- 32.2 vs
148.8 +/- 16.6, P = 0.002), estimated blood loss was higher (102 vs 75 ml, P =
0.06), while hospital stay was shorter and pain score was lower in the
laparoscopy group (P = 0.02) in the laparoscopic group. There were no
intraoperative complications, while the postoperative complication rate was
similar in the two groups (20.8 vs 20.0%). DISCUSSION: Before the laparoscopic
approach became a viable option, endopyelotomy was widely used for managing
recurrent UPJO. However, the success rate of endopyelotomy for secondary UPJO was
approximately 10-25% lower than for open pyeloplasty. Redo pyeloplasty had
excellent results, with reported success rates of 77.8-100%. Laparoscopic redo
pyeloplasty is becoming a viable alternative to open redo pyeloplasty in many
centers with experience in minimally invasive techniques. The present study
revealed that redo laparoscopic pyeloplasty appeared to have advantages over redo
open surgery, in that it was associated with shorter hospital stay (4 vs 6 days,
P = 0.046), reduced postoperative pain score (P = 0.02), and less need for
postoperative analgesia (P = 0.001), still with comparable successful outcomes
and patient safety. However, the procedure had a longer operative times and more
blood loss. CONCLUSION: Laparoscopic pyeloplasty is a viable alternative to open
pyeloplasty in children with recurrent UPJO, with shorter hospital stays and less
postoperative pain. However, the procedure is technically demanding and should be
attempted in high-volume centers by laparoscopists with considerable experience
in laparoscopic reconstructive procedures.
PMID- 27614701
TI - The Lyssavirus glycoprotein: A key to cross-immunity.
AB - Rabies is an acute viral encephalomyelitis in warm-blooded vertebrates, caused by
viruses belonging to Rhabdovirus family and genus Lyssavirus. Although rabies is
categorised as a neglected disease, the rabies virus (RABV) is the most studied
amongst Lyssaviruses which show nearly identical infection patterns. In efforts
to improving post-exposure prophylaxis, several anti-rabies monoclonal antibodies
(mAbs) targeting the glycoprotein (G protein) sites I, II, III and G5 have been
characterized. To explore cross-neutralization capacity of available mAbs and
discover new possible B-cell epitopes, we have analyzed all available
glycoprotein sequences from Lyssaviruses with a focus on sequence variation and
conservation. This information was mapped on the structure of a representative G
protein. We proposed several possible cross-neutralizing B-cell epitopes
(GUVTTTF, WLRTV, REECLD and EHLVVEEL) in complement to the already well
characterized antigenic sites. The research could facilitate development of novel
cross-reactive mAbs against RABV and even more broad, against possibly all
Lyssavirus members.
PMID- 27614700
TI - Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production
and viral gene expression.
AB - Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of
lepidopteran baculoviruses and encodes the protein with the conserved amino acid
residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted
in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in
B. mori cultured cells and larvae, although viral genome replication was not
affected. Bm5 disruption also caused aberrant expression of various viral genes
at the very late stage of infection. Immunocytochemical analysis revealed that
BM5 localized to the nuclear membrane. We also found that DUF3627 is important
for OB production, transcriptional regulation of viral genes, and subcellular
localization of BM5. Compared with wild-type BmNPV infection, larval death was
delayed when B. mori larvae were infected with Bm5 mutants. These results suggest
that BM5 is involved in progeny virus production and regulation of viral gene
expression at the very late stage of infection.
PMID- 27614703
TI - Binding and entry of a non-enveloped T=4 insect RNA virus is triggered by
alkaline pH.
AB - Tetraviruses are small, non-enveloped, RNA viruses that exclusively infect
lepidopteran insects. Their particles comprise 240 copies of a single capsid
protein precursor (CP), which undergoes autoproteolytic cleavage during
maturation. The molecular mechanisms of capsid assembly and maturation are well
understood, but little is known about the viral infectious lifecycle due to a
lack of tissue culture cell lines that are susceptible to tetravirus infection.
We show here that binding and entry of the alphatetravirus, Helicoverpa armigera
stunt virus (HaSV), is triggered by alkaline pH. At pH 9.0, wild-type HaSV virus
particles undergo conformational changes that induce membrane-lytic activity and
binding to Spodoptera frugiperda Sf9 cells. Binding is followed by entry and
infection, with virus replication complexes detected by immunofluorescence
microscopy within 2h post-infection and the CP after 12h. HaSV particles produced
in S. frugiperda Sf9 cells are infectious. Helicoverpa armigera larval virus
biofeed assays showed that pre-treatment with the V-ATPase inhibitor, Bafilomycin
A1, resulted in a 50% decrease in larval mortality and stunting, while incubation
of virus particles at pH 9.0 prior to infection restored infectivity. Together,
these data show that HaSV, and likely other tetraviruses, requires the alkaline
environment of the lepidopteran larval midgut for binding and entry into host
cells.
PMID- 27614705
TI - Literature-based knowledgebase of pancreatic cancer gene to prioritize the key
genes and pathways.
PMID- 27614704
TI - A rare variant in COL11A1 is strongly associated with adult height in Chinese Han
population.
AB - Human height is a highly heritable trait in which multiple genes are involved.
Recent genome-wide association studies (GWASs) have identified that COL11A1 is an
important susceptibility gene for human height. To determine whether the variants
of COL11A1 are associated with adult and children height, we analyzed splicing
and coding single-nucleotide variants across COL11A1 through exome-targeted
sequencing and two validation stages with a total 20,426 Chinese Han samples. A
total of 105 variants were identified by exome-targeted sequencing, of which 30
SNPs were located in coding region. The strongest association signal was
Chr1_103380393 with P value of 4.8 * 10(-7). Chr1_103380393 also showed nominal
significance in the validation stage (P = 1.21 * 10(-6)). Combined analysis of
16,738 samples strengthened the original association of chr1_103380393 with adult
height (Pcombined = 3.1 * 10(-8)), with an increased height of 0.292sd (standard
deviation) per G allele (95% CI: 0.19-0.40). There was no evidence (P = 0.843)
showing that chr1_103380393 altered child height in 3688 child samples. Only the
group of 12-15 years showed slight significance with P value of 0.0258. This
study firstly shows that genetic variants of COL11A1 contribute to adult height
in Chinese Han population but not to children height, which expand our knowledge
of the genetic factors underlying height variation and the biological regulation
of human height.
PMID- 27614702
TI - Inhibition of chikungunya virus by picolinate that targets viral capsid protein.
AB - The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with
the hydrophobic pocket on the surface of capsid protein (CP) plays a critical
role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been
reported to possess antiviral activity against Sindbis Virus (SINV), the
prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the
conserved hydrophobic pocket of capsid protein was analyzed by molecular docking,
isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and
fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1*10(
7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero
cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque
reduction assay, respectively. This study is suggestive of the potential of
pyridine ring compounds as antivirals against alphaviruses and may serve as the
basis for the development of PCA based drugs against alphaviral diseases.
PMID- 27614706
TI - A prospective randomized study comparing the four tract dilation methods of
percutaneous nephrolithotomy.
AB - OBJECTIVE: To compare the one-shot dilation (OSD) technique with three other
dilation techniques namely telescopic Alken, fascial Amplatz and balloon dilation
(BD) in terms of safety efficacy and cost effectiveness. METHODS: During a 31/2
year enrollment period, 480 patients who required PCNL surgery were equally
randomized into four groups. All the cases were assessed preoperatively,
intraoperatively as well as postoperatively till a period of 3 months. Access
time, X-ray exposure time, hemoglobin drop, complications, success rate, etc.,
were all assessed and recorded. RESULTS: Similar preoperative characteristics
were observed in all the four study arms. X-ray exposure time during dilation was
significantly reduced for both OSD and BD when compared to sequential Amplatz and
telescopic Alken dilation (Group ALD = 62.1 + 13, Group AMD = 67.0 + 10, Group
OSD = 36.8 + 7, Group BD = 38.1 + 6, p value = 0.01, post hoc: G4 = G3 < G2 =
G1). There was no significant difference between the access time, hemoglobin
drop, complication and success rates among the groups. BD was the most expensive
dilation method when compared to the other three dilation techniques. CONCLUSION:
All the four methods of dilation are equally safe and effective but both OSD and
BD are advantageous in terms of lesser fluoroscopy time during dilation. OSD is
much cheaper option when compared to BD, and therefore with more experience, it
can become the preferable dilation method, especially in the developing
countries.
PMID- 27614707
TI - Decontamination of stethoscope membranes with chlorhexidine: Should it be
recommended?
AB - OBJECTIVE: To determine differences in the recontamination of stethoscope
membranes after cleaning with chlorhexidine, triclosan, or alcohol. METHODS:
Experimental, controlled, blinded trial to determine differences in the bacterial
load on stethoscope membranes. Membranes were cultured by direct imprint after
disinfection with 70% isopropyl alcohol, 1% triclosan, or 1% chlorhexidine and
normal use for 4 hours. As a baseline and an immediate effect control, bacterial
load of membranes without disinfection and after 1 minute of disinfection with
isopropyl alcohol was determined as well. RESULTS: Three hundred seventy cultures
of in-use stethoscopes were taken, 74 from each arm. In the baseline arm the
median growth was 10 CFU (interquartile range [IQR], 32-42 CFU); meanwhile, in
the isopropyl alcohol immediate-effect arm it was 0 CFU (IQR, 0-0 CFU). In the
arms cultured after 4 hours, a median growth of 8 CFU (IQR, 1-28 CFU) in the
isopropyl alcohol arm, 4 CFU (IQR, 0-17 CFU) in the triclosan arm, and 0 CFU
(IQR, 0-1 CFU) in the chlorhexidine arm were seen. No significant differences
were observed between the bacterial load of the chlorhexidine arm (after 4 hours
of use) and that of the isopropyl alcohol arm (after 1 minute without use) (Z=
2.41; P > .05). CONCLUSIONS: Chlorhexidine can inhibit recontamination of
stethoscope membranes and its use could help avoid cross-infection.
PMID- 27614708
TI - Effects of alcohol-based hand hygiene solutions on breath alcohol detection in
the emergency department.
AB - This study aimed to investigate the effects of alcohol-based hand hygiene
solution (ABHS) use by care providers on point-of-care alcohol breath analyzer
interpretation under different clinically relevant conditions. Among each test
condition (foam vehicle with immediate testing, gel vehicle with immediate
testing, allowing hands to dry after the use of ABHS, and donning gloves after
the use of ABHS), alcohol was detected in breath at 1 minute after use of ABHS.
Because the use of ABHS by individuals administering breath alcohol detection may
result in false-positive detection of alcohol, staff using these devices should
consider traditional hand hygiene with soap and water.
PMID- 27614710
TI - Assessing residual contamination and damage inside flexible endoscopes over time.
AB - Researchers evaluated flexible endoscope damage and contamination levels at
baseline and 2 months later. Postcleaning test results exceeded benchmarks for
all gastroscopes and no colonoscopes. Microbial growth was found in samples from
47% of fully reprocessed endoscopes at baseline and 60% at follow-up. Borescope
examinations identified scratches, discoloration, debris, and fluid inside
endoscopes. Irregularities changed over time. Study evaluations allowed damaged
and contaminated endoscopes to be identified and re-reprocessed or sent for
repairs.
PMID- 27614709
TI - Risk factors of lower respiratory tract infection in patients after tracheal
intubation under general anesthesia in the Chinese health care system: A meta
analysis.
AB - BACKGROUND: Lower respiratory tract infection (LRTI) after tracheal intubation
under general anesthesia poses a serious threat to worldwide health care systems,
especially those in developing countries. However, a significant number of
studies have found inconsistent results in their investigation of the
corresponding risk factors. METHODS: Relevant articles published up to September
2015 were retrieved from PubMed, Ovid, Embase, China National Knowledge
Infrastructure, Chinese Biological Medical Database, China Science and Technology
Journal Database, and Wanfang Data. The z test was used to determine the
significance of the pooled odds ratio (OR). ORs and 95% confidence intervals were
used to compare the risk factors of LRTI after intubation under general
anesthesia. RESULTS: Fifteen case-control studies that included 27,304
participants were identified. We identified the following variables as
independent risk factors: duration of general anesthesia >3 hours (OR, 2.45), age
>60 years (OR, 2.35), normal endotracheal tube (OR, 1.63), deep intubation (OR,
2.66), unpracticed intubation (OR, 2.61), postoperative extubation time >2 hours
(OR, 3.76), smoking history (OR, 3.02), chronic respiratory disease history (OR,
2.30), incomplete extubation indication (OR, 3.54), thoracic or craniocerebral
surgery (OR, 1.90), and emergent surgery (OR, 2.54). CONCLUSIONS: Eleven risk
factors, including surgery, anesthesia, and health condition, were related to
LRTI after intubation under general anesthesia. Given the limitations of this
study, well-designed epidemiologic studies with a large sample size should be
performed in the future.
PMID- 27614712
TI - Prognostic and pathophysiological marker for patients with chronic thromboembolic
pulmonary hypertension: Usefulness of diffusing capacity for carbon monoxide at
diagnosis.
AB - BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH)
is a progressive disease in some patients, despite improved treatments.
Microvasculopathy has been implicated in the poor outcomes of patients with
CTEPH. A reduction in the diffusing capacity for carbon monoxide (DLCO ) was
previously suggested to indicate microvasculopathy in CTEPH patients; therefore,
we assessed DLCO /alveolar ventilation (DLCO /VA ) as a prognostic and
pathophysiological marker in CTEPH. METHODS: We performed a retrospective cohort
study of 214 CTEPH patients consecutively diagnosed between 1986 and 2011. After
exclusion of 24 patients because of missing DLCO data or severe obstructive
impairment, the mortality rates of medically treated patients classified with
normal or decreased DLCO values were compared, and prognostic factors were
determined. The relationship between long-term surgical outcomes and DLCO /VA was
also investigated. RESULTS: Ninety-one inoperable patients were treated
medically, two of whom underwent balloon pulmonary angioplasty. Ninety-nine
underwent pulmonary endarterectomy. The 5-year survival rate of medically treated
patients was significantly lower in patients with decreased DLCO /VA than in
those with normal values (61.4% vs 90.4%, P = 0.017). Decreased preoperative DLCO
/VA was associated with a smaller percent decrease in post-operative pulmonary
vascular resistance, but not with the extent of proximal thrombi; these results
may support our hypothesis that DLCO reflects microvascular involvement.
CONCLUSION: Decreased DLCO /VA was associated with poor outcomes of medically
treated CTEPH patients; and may be useful for identifying high-risk patients,
potentially leading to earlier and more appropriate interventions.
PMID- 27614711
TI - Exploiting the Achilles' heel of membrane trafficking in trypanosomes.
AB - Pathogenic protozoa are evolutionarily highly divergent from their metazoan
hosts, reflected in many aspects of their biology. One particularly important
parasite taxon is the trypanosomatids. Multiple transmission modes, distinct life
cycles and exploitation of many host species attests to great prowess as
parasites, and adaptability for efficient, chronic infection. Genome sequencing
has begun uncovering how trypanosomatids are well suited to parasitism, and
recent genetic screening and cell biology are revealing new aspects of how to
control these organisms and prevent disease. Importantly, several lines of
evidence suggest that membrane transport processes are central for the
sensitivity towards several frontline drugs.
PMID- 27614714
TI - The Heme-Based Oxygen Sensor Rhizobium etli FixL: Influence of Auxiliary Ligands
on Heme Redox Potential and Implications on the Enzyme Activity.
AB - Conformational changes associated to sensing mechanisms of heme-based protein
sensors are a key molecular event that seems to modulate not only the protein
activity but also the potential of the FeIII/II redox couple of the heme domain.
In this work, midpoint potentials (Em) assigned to the FeIII/II redox couple of
the heme domain of FixL from Rhizobium etli (ReFixL) in the unliganded and
liganded states were determined by spectroelectrochemistry in the presence of
inorganic mediators. In comparison to the unliganded ReFixL protein (+19mV), the
binding to ligands that switch off the kinase activity induces a negative shift,
i. e. Em=-51, -57 and -156mV for O2, imidazole and CN-, respectively. Upon
binding to CO, which does not affect the kinase active, Em was observed at +21mV.
The potential values observed for FeIII/II of the heme domain of ReFixL upon
binding to CO and O2 do not follow the expected trend based on thermodynamics,
assuming that positive potential shift would be expected for ligands that bind to
and therefore stabilize the FeII state. Our results suggest that the
conformational changes that switch off kinase activity upon O2 binding have knock
on effects to the local environment of the heme, such as solvent rearrangement,
destabilize the FeII state and counterbalances the FeII-stabilizing influence of
the O2 ligand.
PMID- 27614713
TI - Effects of alpha-melanocyte-stimulating hormone on mitochondrial energy
metabolism in rats of different age-groups.
AB - Hypothalamic alpha-melanocyte-stimulating hormone (alpha-MSH) is a key catabolic
mediator of energy homeostasis. Its anorexigenic and hypermetabolic effects show
characteristic age-related alterations that may be part of the mechanism of
middle-aged obesity and geriatric anorexia/cachexia seen in humans and other
mammals. We aimed to investigate the role of alpha-MSH in mitochondrial energy
metabolism during the course of aging in a rodent model. To determine the role of
alpha-MSH in mitochondrial energy metabolism in muscle, we administered
intracerebroventricular (ICV) infusions of alpha-MSH for 7-days to different age
groups of male Wistar rats. The activities of oxidative phosphorylation complexes
I to V and citrate synthase were determined and compared to those of age-matched
controls. We also quantified mitochondrial DNA (mtDNA) copy number and measured
the expression of the master regulators of mitochondrial biogenesis, peroxisome
proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and
peroxisome proliferator-activated receptor gamma (PPARgamma). The peptide reduced
weight gain in juvenile rats to one fifth of that of controls and increased the
weight loss in older animals by about five fold. Mitochondrial DNA copy number
inversely correlated with changes in body weight in controls, but not in alpha
MSH-treated animals. The strong increase in body weight in young rats was
associated with a low mtDNA copy number and high PPARgamma mRNA levels in
controls. Expression of PGC-1alpha and PPARgamma declined with age, whereas
OXPHOS and citrate synthase enzyme activities were unchanged. In contrast, alpha
MSH treatment suppressed OXPHOS enzyme and citrate synthase activity. In
conclusion, our results showed age-related differences in the metabolic effects
of alpha-MSH. In addition, administration of alpha-MSH suppressed citrate
synthase and OXPHOS activities independent of age. These findings suggest that
alpha-MSH exposure may inhibit mitochondrial biogenesis.
PMID- 27614715
TI - Globin domain interactions control heme pocket conformation and oligomerization
of globin coupled sensors.
AB - Globin coupled sensors (GCS) are O2-sensing proteins used by bacteria to monitor
the surrounding gaseous environment. To investigate the biphasic O2 dissociation
kinetics observed for full-length GCS proteins, isolated globin domains from
Pectobacterium carotovorum ssp. carotovorum (PccGlobin), and Bordetella pertussis
(BpeGlobin), have been characterized. PccGlobin is found to be dimeric, while
BpeGlobin is monomeric, indicating key differences in the globin domain dimer
interface. Through characterization of wild type globin domains and globin
variants with mutations at the dimer interface and within the distal pocket,
dimerization of the globin domain is demonstrated to correlate with biphasic
dissociation kinetics. Furthermore, a distal pocket tyrosine is identified as the
primary hydrogen bond donor, while a secondary hydrogen bond donor within the
distal heme pocket is involved in conformation(s) that lead to the second O2
dissociation rate. These findings highlight the role of the globin dimer
interface in controlling properties of both the heme pocket and full-length GCS
proteins.
PMID- 27614716
TI - Sagittal plane kinematics predict kinetics during walking gait in individuals
with anterior cruciate ligament reconstruction.
AB - BACKGROUND: Alterations in mechanical loading following anterior cruciate
ligament reconstruction may lead to the development of knee osteoarthritis.
Feedback that cues a change in knee kinematics during walking gait may influence
mechanical loading, yet it remains unknown if knee kinematics predict kinetics
during walking gait. Our aim was to determine if sagittal plane knee kinematics
predict kinetics during walking gait in anterior cruciate ligament reconstructed
individuals. METHODS: Forty-one individuals with a history of primary, unilateral
anterior cruciate ligament reconstruction completed a motion capture walking gait
analysis. Hierarchical linear regression analyses were used in order to determine
the amount of variance in the kinetic variables of interest (peak vertical ground
reaction force, instantaneous and linear vertical ground reaction force loading
rate) that was individually predicted by the kinematic variables of interest
(knee flexion angle at heelstrike, peak knee flexion angle, and knee flexion
excursion). FINDINGS: Knee flexion excursion of the injured limb significantly
predicted 11% of the variance in peak vGRF of the injured limb after accounting
for gait speed and peak knee flexion angle (DeltaR2=0.11, P=0.004). After
accounting for gait speed and knee flexion angle at heelstrike, knee flexion
excursion significantly predicted 16% of the variance in the injured limb peak
vertical ground reaction force (DeltaR2=0.16, P=0.001). No kinematic variable
predicted vertical ground reaction force loading rate. INTERPRETATION: Altering
knee flexion excursion may be useful as a future therapeutic target for modifying
peak vertical ground reaction force during walking gait following anterior
cruciate ligament reconstruction.
PMID- 27614717
TI - Outcome of 122 delayed breast reconstruction following post-mastectomy
radiotherapy: The scarless latissimus dorsi flap with tissue expansion technique.
AB - BACKGROUND: Delayed breast reconstruction with tissue expansion may be risky
after radiotherapy, due to the poor skin quality. To permit the use of the tissue
expansion procedure, we propose a scarless latissimus dorsi flap to bring tissue
trophicity, by a healthy vascularized muscular interface with no donor scar and
no patch effect. The objective of this study is to assess the outcome of the
tissue expansion technique with scarless latissimus dorsi flap after post
mastectomy radiotherapy. METHODS: All the patients who had benefited of a delayed
breast reconstruction after radiotherapy using tissue expansion technique with
scarless latissimus dorsi flap, between January 2000 and January 2013, were
reviewed. The exclusion criteria were: prior breast reconstruction, or
interruption of breast reconstruction procedure due to active metastatic disease
requiring ongoing oncological treatment. The complications were identified:
failures of reconstruction, implant exposure, wound dehiscence, capsular
contracture, deflation of implant, hematoma, infection, and skin necrosis.
RESULTS: One hundred and twenty-two breasts were reviewed. The average time
between the flap and the expander intervention was: 194+/-114 SD (28-1051) days.
The mean volume of inserted expander was 633+/-111 SD (350-1100) mL and the mean
inflation volume was 578+/-190 SD (170-1160) mL. The average time between
insertion of the expander and insertion of the permanent implant was 132+/-76 SD
(49-683) days. The mean inflation of the implant volume was 368+/-105 SD (130
620) mL. Forty patients developed at least one complication. The most common
complication was the appearance of a capsular contracture requiring a
capsulectomy: 11 (9.2%) with permanent implants and 6 (4.9%) with expander.
Deflation of implants occurred with six permanent implants and with one expander.
There were 3 breast reconstructions failures (two infections and one exposure of
implants). CONCLUSION: This procedure offers the advantages that there is no
unattractive scar, and that there are low rates of exposure or failed
reconstruction.
PMID- 27614718
TI - [Emergency management of extravasation in children].
AB - The subcutaneous diffusion of intravenous drips, or extravasation, is a frequent
iatrogenic complication in children, mainly in the neonatal period. This
potentially severe pathology can lead to local ischemia that sometimes mimics
compartment syndrome. It can also evolve towards vast soft-tissue necrosis.
Nursing staff often underestimate the risk of functional, aesthetic, and
psychological consequences. The speed and quality of the initial medical and
surgical management can greatly decrease morbidity associated with extravasation.
Prevention is fundamental, such as raising awareness in and training medical and
paramedical staffs and creating efficient protocols. Surgical management
involving aspiration and washing the site as early as possible improves the
prognosis. Aspiration and washing can be done on a larger area if one criteria of
severity is met, particularly in cases of extravasation using a vesicant or
hyperosmolar agent. If necrotic lesions appear, it is wise to wait until they
become delimited. Debridement and coverage can be performed using classical
methods.
PMID- 27614720
TI - [Surgical management of a series of pressure ulcers: Report of 61 cases].
AB - INTRODUCTION: Retrospective study about pressure ulcers surgical treatments in a
series of 61 in 43 patients. OBJECTIVE: To assess the management of pressure
ulcers in spinal cord injury patients who had been operated in our institution.
RESULTS: On the 61 pressure ulcers, location was ischial in 35 cases, sacral in
15 cases, trochanteric in 7 cases, lateral malleolar in 2 cases, on the heel in 1
case, and 1 was located lateral to the fibular head. Comorbidities were searched
pre- and postoperatively. Fifty-five muscular, cutaneous flaps or myocutaneous, 5
fasciocutaneous and 1 excision/suture were realized. The mean follow-up was 8.6
years, and we observed 9 pressure ulcers recurrences (14.8%). We had a total
result of 15 (24.6%) complicated pressure ulcers, with 8 early complications
(13.1%) and 7 delay (11.5%). Antibiotic therapy was prescribed in 54 (88.5%)
surgery cases and 7 were operated without any (11.5%). CONCLUSION: Pressure
ulcers are major public health focus that need to be improved. A
multidisciplinary care, mixed with education of patients are mandatory to achieve
these goals: reduce complications and recurrences. Thanks to muscle sparring,
perforators flap should become the gold standard of pressure ulcers surgery.
PMID- 27614719
TI - [Facial trauma and injury in children].
AB - Facial traumas are common in children but often unconsidered. Facial injury is
responsible of impressive bleeding because of the rich vascularization of the
face; this bleeding is often underestimated because of the immediate arterial
vasoconstriction that is very strong for children. The blood volume is 80ml/kg
for a newborn, with a total of 250ml, reaching 70ml/kg at one year of age. The
evaluation must be rigorously performed due to the risk of a sudden
decompensation. Regarding the wounds, the primary repair must be performed
directly neat or optimal in case of damaged tissues. The rule is to keep maximum
of the integrity and to limit debridement. Careful repair often requires general
anesthesia, especially in young children, to facilitate a perfect joining of the
edges and of the mucocutaneous lines. Losses of substance should be treated by
directed cicatrization. Flaps are never performed in children as a first
intention for reasons developed below. Given the elasticity of the facial
skeleton, fractures require a brutal shock to occur, but the clinical signs can
be misleading. For instance, too specific and sometimes ignored, fractures can
show weakly symptomatic signs : the fractures of the condylar and the orbital
floor, with their respective complication that are temporomandibular bone
ankylosis and definitive diplopia. Possible children abuse should be suspected in
case of different age lesions and discrepancies between the told story and types
of injuries. Once the vital urgency is eliminated, the orbital emergency should
be first considered in facial traumas within the ophthalmology specialty because
wounds and contusions of the globe are often under-evaluated and threaten the
vision. The second emergency is the orbital floor fracture in its 'trapdoor'
type, specific to the child. Combined with a motionless eye and uncontrollable
vomiting, this is the second true urgency because it involves the prognosis of
the oculomotricity and requires emergency surgery. Finally, dental trauma should
not be overlooked because of their functional and aesthetic consequences. Primary
cicatrization is usually rapid but scars remain inflammatory during a long time.
The risk of hypertrophy exists in case of contusions and lacerations associated
with wounds but also during puberty and in some locations. Age interfere with the
result because growth will either improve or worsen the initial result, depending
on the location and mechanism. The secondary specialized and prolonged managing
and monitoring is capital on the functional, aesthetic and psychological points
of view.
PMID- 27614721
TI - [Auricular malformations].
AB - Reconstruction of complex auricular malformations is one of the longest surgical
technique to master, because it requires an extremely detailed analysis of the
anomaly and of the skin potential, as well as a to learn how to carve a complex
3D structure in costal cartilage. Small anomalies can be taken care of by any
plastic surgeon, providing that he/she is aware of all the refinements of ear
surgery. In this chapter, we analyze retrospectively 30 years of auricular
reconstruction, ranging from small anomalies to microtia (2500 cases), excluding
aesthetics variants such as prominent ears.
PMID- 27614722
TI - Termination of atrial spiral waves by traction into peripheral non 1:1 conducting
regions - A numerical study.
AB - Atrial ablation has been recently utilized to treat atrial fibrillation (AF) by
isolation or destruction of arrhythmia drivers. In chronic or persistent AF
patients these drivers often consist of one or few rotors at unknown locations,
and several ablations are commonly conducted before arrhythmia is terminated.
However, the irreversible damage done to the tissue may lead to AF recurrence. We
propose an alternative strategy to terminate rotor activity by its attraction
into a non 1:1 conducting region. The feasibility of the method was numerically
tested in 2D models of chronic AF human atrial tissue. Left-to-right gradients of
either acetylcholine (ACh) or potassium conductance were employed to generate
regions of 1:1 and non 1:1 conduction, characterized by their dominant frequency
(DF) ratios. Spiral waves were established in the 1:1 conducting region and
raster scanning was employed using a stimulating probe to attract the spiral wave
tip. The probe was then linearly moved towards the boundary between the two
regions. Successful attraction of spiral waves to the probe was demonstrated when
the probe was <8mm from the spiral wave tip. Maximal traction velocity without
loss of anchoring increased in a non-linear way with increasing values of ACh.
Success rate of spiral wave termination was over 90% for regional DF ratios of as
low as 1:1.2. Given that normally much higher ratios are measured in
physiological atrial tissues, we envision this technique to provide a feasible,
safer alternative to ablation procedures performed in persistent AF patients.
PMID- 27614723
TI - Efficacy Profile of Ivabradine in Patients with Heart Failure plus Angina
Pectoris.
AB - OBJECTIVES: In the Systolic Heart Failure Treatment with the If Inhibitor
Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced
cardiovascular death or heart failure hospitalizations among patients with
systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the
Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with
Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without
CHF provided no benefit for cardiovascular death or nonfatal myocardial
infarction (primary composite end point), with secondary analyses suggesting
possible harm in the angina subgroup. Therefore, we examined the impact of
ivabradine in the patients with CHF plus angina in SHIFT. METHODS: SHIFT enrolled
adults with stable, symptomatic CHF, a left ventricular ejection fraction <=35%
and a sinus rhythm with a resting heart rate >=70 bpm. Outcomes were the SHIFT
and SIGNIFY primary composite end points and their components. RESULTS: Of 6,505
patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine
numerically, but not significantly, reduced the SIGNIFY primary composite end
point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and
overall population, respectively. Ivabradine also reduced the SHIFT primary
composite end point in all 3 subgroups. CONCLUSIONS: In SHIFT, ivabradine showed
consistent reduction of cardiovascular outcomes in patients with CHF; similar
results were seen in the subgroup of SHIFT patients with angina.
PMID- 27614724
TI - Renal denervation in the treatment of resistant hypertension: Dead, alive or
surviving?
AB - Hypertension is one of the most common chronic clinical problems encountered by
physicians. The prevalence of resistant hypertension is estimated at 9% in the
US. Patients with resistant hypertension have been shown to be at higher risk for
adverse cardiovascular events, hence the need for greater efforts in improving
the treatment of hypertension. The renal sympathetic nerves play an important
role in the development of hypertension, mediated via sodium and water retention,
increased renin release and alterations in renal blood flow. The proximity of the
afferent and efferent renal sympathetic nerves to the adventitia of the renal
arteries suggested the feasibility of an endovascular, selective, minimally
invasive approach to renal denervation; a potential treatment option for
resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and
Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation
in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15
and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials
are needed to ascertain the benefits or otherwise of renal denervation in
treatment-resistant hypertension.
PMID- 27614725
TI - Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in
bone deteriorations of type 1 diabetic mice with estrogen deficiency.
AB - AIMS: This study was aimed to investigate the involvement of skeletal renin
angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations
of mice in response to the combination treatment of estrogen deficiency and
hyperglycemia. METHODS: The female C57BL/6J mice were sham-operated or
ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later,
the biochemistries in serum and urine were determined by standard colorimetric
methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal
metaphysis. The polymerase chain reaction and immunoblotting were applied for
molecular analysis on mRNA and protein expression. RESULTS: The mice after
treating with ovariectomy and STZ showed the decreased level of serum Ca and the
increased level of serum PTH and urine Ca. The H&E staining showed trabecular
bone abnormalities as demonstrated by the loss, disconnection and separation of
trabecular bone network as well as the loss of chondrocytes and appearance of
chondrocyte cluster at growth plate of tibia. The significant increase of matured
osteoclast number was shown in group with double treatments. The combination
treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor,
MMP-9 and CAII, and protein expression of renin, and decreased the ratio of
OPG/RANKL and the expression of bradykinin receptors in bone tissue. CONCLUSION:
Ovariectomy combined with STZ induction produced more detrimental actions on bone
through the activation of local bone RAS and the down-regulation of bradykinin
receptors, as compared to the respective single treatment.
PMID- 27614726
TI - Distinct biomarker roles for HbA1c and glycated albumin in patients with type 2
diabetes on hemodialysis.
AB - AIMS: HbA1c and glycated albumin (GA) are used to monitor glycemia, but their
accuracy to represent glycemic profiles in hemodialysis remains controversial.
METHODS: Continuous glucose monitoring in 97 patients with type 2 diabetes (41 on
hemodialysis [HD] and 56 without nephropathy) was analyzed to evaluate whether
HbA1c and/or GA serve as appropriate glycemic profile markers. RESULTS: The
average glucose significantly correlated with HbA1c in both HD group and group
without nephropathy (r=0.59, P<0.0001; r=0.40, P<0.005). The slopes of linear
regression lines were statistically indistinguishable (F=0.30, P=0.744), while
the y-intercepts were significantly different (F=57.86, P<0.0001). GA showed
strong correlation with the glycemic standard deviation (r=0.68, P<0.0001), and
with the average glucose (r=0.42, P<0.001). Least square analysis revealed that
only HbA1c, but not GA, was significantly associated with the average glucose
(F=10.20, P<0.0005; F=0.38, P=0.5427), while only GA was significantly associated
with the glycemic variability in HD group. CONCLUSIONS: In HD participants, HbA1c
correlates with the average glucose more than GA, but underestimates it, and a
correction formula of HbA1c can be developed as an appreciable marker. GA value
itself reflects the average glucose, but less accurately than HbA1c, while it
could serve as an indicator for hyperglycemia/hypoglycemia excursion.
PMID- 27614727
TI - Effects of Mediterranean diet on sexual function in people with newly diagnosed
type 2 diabetes: The MEDITA trial.
AB - AIMS: To assess the long-term effect of Mediterranean diet, as compared with low
fat diet, on sexual function in patients with newly diagnosed type 2 diabetes.
METHODS: In a randomized clinical trial, with a total follow-up of 8.1years, 215
men and women with newly diagnosed type 2 diabetes were assigned to Mediterranean
diet (n=108) or a low-fat diet (n=107). The primary outcome measures were changes
of erectile function (IIEF) in diabetic men and of female sexual function (FSFI)
in diabetic women. RESULTS: There was no difference in baseline sexual function
in men (n=54 vs 52) or women (n=54 vs 55) randomized to Mediterranean diet or low
fat diet, respectively (P=0.287, P=0.815). Over the entire follow-up, the changes
of the primary outcomes were significantly lower in the Mediterranean diet group
compared with the low-fat group: IIEF and FSFI showed a significantly lesser
decrease (1.22 and 1.18, respectively, P=0.024 and 0.019) with the Mediterranean
diet. Baseline C-reactive protein levels predicted erectile dysfunction in men
but not female sexual dysfunction in women. CONCLUSIONS: Among persons with newly
diagnosed type 2 diabetes, a Mediterranean diet reduced the deterioration of
sexual function over time in both sexes.
PMID- 27614728
TI - Different antibiotic treatments for group A streptococcal pharyngitis.
AB - BACKGROUND: Antibiotics provide only modest benefit in treating sore throat,
although effectiveness increases in participants with positive throat swabs for
group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is
the best choice if antibiotics are indicated. OBJECTIVES: To assess the evidence
on the comparative efficacy of different antibiotics in: (a) alleviating symptoms
(pain, fever); (b) shortening the duration of the illness; (c) preventing
relapse; and (d) preventing complications (suppurative complications, acute
rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence
on the comparative incidence of adverse effects and the risk-benefit of
antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched
CENTRAL (2016, Issue 3), MEDLINE Ovid (1946 to March week 3, 2016), Embase
Elsevier (1974 to March 2016), and Web of Science Thomson Reuters (2010 to March
2016). We also searched clinical trials registers. SELECTION CRITERIA:
Randomised, double-blind trials comparing different antibiotics and reporting at
least one of the following: clinical cure, clinical relapse, or complications or
adverse events, or both. DATA COLLECTION AND ANALYSIS: Two review authors
independently screened trials for inclusion, and extracted data using standard
methodological procedures as recommended by Cochrane. We assessed risk of bias of
included studies according to the methods outlined in the Cochrane Handbook for
Systematic Reviews of Interventions and used the GRADE tool to assess the overall
quality of evidence for the outcomes. MAIN RESULTS: We included 19 trials (5839
randomised participants); seven compared penicillin with cephalosporins, six
compared penicillin with macrolides, three compared penicillin with carbacephem,
one trial compared penicillin with sulphonamides, one trial compared clindamycin
with ampicillin, and one trial compared azithromycin with amoxicillin in
children. All included trials reported clinical outcomes. Reporting of
randomisation, allocation concealment, and blinding was poor in all trials. The
overall quality of the evidence assessed using the GRADE tool was low for the
outcome 'resolution of symptoms' in the intention-to-treat (ITT) analysis and
very low for the outcomes 'resolution of symptoms' of evaluable participants and
for adverse events. We downgraded the quality of evidence mainly due to lack of
(or poor reporting of) randomisation or blinding, or both, heterogeneity, and
wide confidence intervals (CIs).There was a difference in symptom resolution in
favour of cephalosporins compared with penicillin (evaluable patients analysis
odds ratio (OR) for absence of resolution of symptoms 0.51, 95% CI 0.27 to 0.97;
number needed to treat to benefit (NNTB) 20, N = 5, n = 1660; very low quality
evidence). However, this was not statistically significant in the ITT analysis
(OR 0.79, 95% CI 0.55 to 1.12; N = 5, n = 2018; low quality evidence). Clinical
relapse was lower for cephalosporins compared with penicillin (OR 0.55, 95% CI
0.30 to 0.99; NNTB 50, N = 4, n = 1386; low quality evidence), but this was found
only in adults (OR 0.42, 95% CI 0.20 to 0.88; NNTB 33, N = 2, n = 770). There
were no differences between macrolides and penicillin for any of the outcomes.
One unpublished trial in children found a better cure rate for azithromycin in a
single dose compared to amoxicillin for 10 days (OR 0.29, 95% CI 0.11 to 0.73;
NNTB 18, N = 1, n = 482), but there was no difference between the groups in ITT
analysis (OR 0.76, 95% CI 0.55 to 1.05; N = 1, n = 673) or at long-term follow-up
(evaluable patients analysis OR 0.88, 95% CI 0.43 to 1.82; N = 1, n = 422).
Children experienced more adverse events with azithromycin compared to
amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; N = 1, n = 673). Compared with
penicillin carbacephem showed better symptom resolution post-treatment in adults
and children combined (ITT analysis OR 0.70, 95% CI 0.49 to 0.99; NNTB 14, N = 3,
n = 795), and in the subgroup analysis of children (OR 0.57, 95% CI 0.33 to 0.99;
NNTB 8, N = 1, n = 233), but not in the subgroup analysis of adults (OR 0.75, 95%
CI 0.46 to 1.22, N = 2, n = 562). Children experienced more adverse events with
macrolides compared with penicillin (OR 2.33, 95% CI 1.06 to 5.15; N = 1, n =
489). Studies did not report on long-term complications so it was unclear if any
class of antibiotics was better in preventing serious but rare complications.
AUTHORS' CONCLUSIONS: There were no clinically relevant differences in symptom
resolution when comparing cephalosporins and macrolides with penicillin in the
treatment of GABHS tonsillopharyngitis. Limited evidence in adults suggests
cephalosporins are more effective than penicillin for relapse, but the NNTB is
high. Limited evidence in children suggests carbacephem is more effective than
penicillin for symptom resolution. Data on complications are too scarce to draw
conclusions. Based on these results and considering the low cost and absence of
resistance, penicillin can still be regarded as a first choice treatment for both
adults and children. All studies were in high-income countries with low risk of
streptococcal complications, so there is need for trials in low-income countries
and Aboriginal communities where risk of complications remains high.
PMID- 27614729
TI - Hollow silica microspheres for buoyancy-assisted separation of infectious
pathogens from stool.
AB - Separation of cells and microorganisms from complex biological mixtures is a
critical first step in many analytical applications ranging from clinical
diagnostics to environmental monitoring for food and waterborne contaminants.
Yet, existing techniques for cell separation are plagued by high reagent and/or
instrumentation costs that limit their use in many remote or resource-poor
settings, such as field clinics or developing countries. We developed an
innovative approach to isolate infectious pathogens from biological fluids using
buoyant hollow silica microspheres that function as "molecular buoys" for
affinity-based target capture and separation by floatation. In this process,
antibody functionalized glass microspheres are mixed with a complex biological
sample, such as stool. When mixing is stopped, the target-bound, low-density
microspheres float to the air/liquid surface, which simultaneously isolates and
concentrates the target analytes from the sample matrix. The microspheres are
highly tunable in terms of size, density, and surface functionality for targeting
diverse analytes with separation times of <=2min in viscous solutions. We have
applied the molecular buoy technique for isolation of a protozoan parasite that
causes diarrheal illness, Cryptosporidium, directly from stool with separation
efficiencies over 90% and low non-specific binding. This low-cost method for
phenotypic cell/pathogen separation from complex mixtures is expected to have
widespread use in clinical diagnostics as well as basic research.
PMID- 27614730
TI - Separation of thorium and uranium in nitric acid solution using silica based
anion exchange resin.
AB - To separate thorium and uranium in nitric acid solution using anion exchange
process, a strong base silica-based anion exchange resin (SiPyR-N4) was
synthesized. Batch experiments were conducted and the separation factor of
thorium and uranium in 9M nitric acid was about 10. Ion exchange chromatography
was applied to separate thorium and uranium in different ratios. Uranium could be
eluted by 9M nitric acid and thorium was eluted by 0.1M nitric acid. It was
proved that thorium and uranium can be separated and recovered successfully by
this method.
PMID- 27614731
TI - Comparison of the performance of forward fill/flush and reverse fill/flush flow
modulation in comprehensive two-dimensional gas chromatography.
AB - The performances of forward flow fill and flush (FFF) and of reverse flow fill
and flush (RFF) in flow modulated comprehensive two-dimensional gas
chromatography (GC*GC) using the same volume of the sampling channel have been
studied and compared. Sample models include a reference mixture of hydrocarbons
at low concentration, a petroleum reformate product and the essential oil of Rosa
damascena Miller. The latter samples contain solutes in different concentrations
but some up to 30% allowing to study overloading phenomena in detail. For solutes
injected at low quantity, the performance of FFF and RFF is similar. For solutes
present in a sample at high quantity, RFF guarantees less broadening and
spreading resulting in better quantitation.
PMID- 27614732
TI - Pirkle-type chiral stationary phase on core-shell and fully porous particles: Are
superficially porous particles always the better choice toward ultrafast high
performance enantioseparations?
AB - Pirkle-type Whelk-O1 chiral stationary phase (CSP) was prepared on 2.6MUm
superficially porous particles (SPPs). The chromatographic behavior of columns
packed with this new CSP was compared with that of columns packed respectively
with 1.8 and 2.5MUm Whelk-O1 fully porous particles (FPPs). In the comparison,
both thermodynamic and kinetic aspects were considered. Contrary to initial
expectations, chiral columns packed with 2.6MUm SPPs were quasi-comparable to
those packed with 2.5MUm FPPs, apparently due to larger contributions to band
broadening from both eddy dispersion and, especially for the second eluted
enantiomer, adsorption-desorption kinetics. These findings raise the question if
SPPs, in spite of the undeniable advantages of their morphology to speed up mass
transfer, are always the best choice for high-efficient ultrafast chiral
separations. The last part of the work focuses on the use of short columns (10mm
long) and very high flow rates to realize the separation of the enantiomers of
trans-stilbene oxide (TSO) in normal phase mode in less than 1s.
PMID- 27614733
TI - [Radiotherapy in retroperitoneal sarcomas].
PMID- 27614734
TI - Combined IKZF1 and IG markers as new tools for diagnosis and minimal residual
disease assessment in Tunisian B-ALL.
AB - INTRODUCTION: The monitoring of minimal residual disease (MRD) approach in
patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early
detection of residual clones inducing relapses and therefore appropriate therapy
strategy. The molecular markers may identify and quantify the residual blasts in
B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH
and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample
using MLPA, multiplex PCR and real-time quantitative PCR. MATERIAL: We showed
that multiplex PCR and MLPA are necessary and complementary to detect IKZF1
deletions. RESULTS: We have identified at the diagnosis clonal IGH rearrangement
(VH3-JH5) and IKZF1 deletion (Delta4-7), which we have used it for MRD evaluation
after induction chemotherapy. Despite the absence of chromosome abnormality, the
patient may be classified in high-risk group with a relapse rate of residual
blasts>10-4 and sensitivity up to 10-5. This molecular approach enabled the
patient's stratification, which was overlooked by classical methods. CONCLUSION:
The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular
tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a
routine tests in Tunisian clinical laboratories. They will be useful to stratify
patients into risk groups leading to better treatment strategy.
PMID- 27614735
TI - Reflectance Confocal Microscopy in Lentigo Maligna.
AB - Lentigo maligna is the most common type of facial melanoma. Diagnosis is
complicated, however, as it shares clinical and dermoscopic characteristics with
other cutaneous lesions of the face. Reflectance confocal microscopy is an
imaging technique that permits the visualization of characteristic features of
lentigo maligna. These include a disrupted honeycomb pattern and pagetoid cells
with a tendency to show folliculotropism. These cells typically have a dendritic
morphology, although they may also appear as round cells measuring over 20MUm
with atypical nuclei. Poorly defined dermal papillae and atypical cells may be
seen at the dermal-epidermal junction and can form bridges resembling
mitochondrial structures. Other characteristic findings include junctional
swelling with atypical cells located around the follicles, resembling caput
medusae. Reflectance confocal microscopy is a very useful tool for diagnosing
lentigo maligna.
PMID- 27614736
TI - Donation After Circulatory Death Lungs Transplantable Up to Six Hours After Ex
Vivo Lung Perfusion.
AB - BACKGROUND: Despite the critical need for donor lungs, logistic and geographic
barriers hinder lung utilization. We hypothesized that lungs donated after
circulatory death subjected to 6 hours of cold preservation after ex vivo lung
perfusion (EVLP) would have similar outcomes after transplantation as lungs
transplanted immediately after EVLP, and that both would perform superiorly
compared with lungs transplanted immediately after procurement. METHODS: Donor
porcine lungs were procured after circulatory death and 15 minutes of warm
ischemia. Three groups (n = 5 per group) were randomized: immediate left lung
transplantation (Immediate group), EVLP for 4 hours followed by transplantation
(EVLP group), or EVLP for 4 hours followed by 6 hours of cold preservation
followed by transplantation (EVLP+Cold group). Lungs were reperfused for 2 hours
before obtaining pulmonary vein samples for partial pressure of oxygen/fraction
of inspired oxygen ratio calculations, airway pressures for compliance
measurements, and wet/dry weight ratios. RESULTS: The partial pressure of
oxygen/fraction of inspired oxygen ratios in the EVLP and EVLP+Cold groups were
significantly improved compared with those in the Immediate group (429.7 +/- 51.8
and 436.7 +/- 48.2 versus 117.4 +/- 22.9 mm Hg, respectively). In addition,
dynamic compliance was significantly improved in the EVLP and EVLP+Cold groups
compared with immediate group (26.2 +/- 4.2 and 27.9 +/- 3.5 versus 11.1 +/- 2.4
mL/cmH2O, respectively). There were no differences in oxygenation capacity or
dynamic compliance between the EVLP and EVLP+Cold groups. Inflammatory cytokine
levels were significantly lower in the EVLP and EVLP+Cold groups. CONCLUSIONS:
Lungs donated after circulatory death can be successfully transplanted as much as
6 hours after EVLP. Cold preservation of lungs after ex vivo assessment and
rehabilitation may improve organ allocation, even to distant recipients, without
compromising allograft function.
PMID- 27614737
TI - Impact of Changes in Left Ventricular Ejection Fraction on Survival After
Transapical Aortic Valve Implantation.
AB - BACKGROUND: This single-center retrospective study assessed the variation of left
ventricular ejection fraction (LVEF) after transapical transcatheter aortic valve
implantation and its effect on survival. We also evaluated the effect of sheath
diameter on LVEF. METHODS: We analyzed data of all consecutive patients who
underwent transapical transcatheter aortic valve implantation with the Sapien
(Edwards Lifesciences, Irvine, CA) device (and its evolutions) between 2009 and
2015. We analyzed the difference between preoperative LVEF and LVEF at discharge
(DeltaEF = LVEFpost-op - LVEFpre-op) and considered its interquartile range (+/
5%) as the cutoff. Patients were divided in three groups: (1) improved LVEF
(DeltaEF >= +5%); (2) unchanged LVEF (DeltaEF -5% to +5%), and (3) worsened LVEF
(DeltaEF <= -5%). Survival was evaluated with Kaplan-Meier analysis, and logistic
regression multivariable analysis was used to determine independent predictors of
LVEF improvement. RESULTS: Data of 122 patients were analyzed. Patients in the
three groups were distributed as follows: (group 1) 27 patients (22.1%), (group
2) 69 (56.6%), and (group 3) 26 (21.3%). The mean DeltaEF was 12.7% +/- 4.7% in
group 1 and -10.8% +/- 3.9% in group 3. The DeltaEF was more likely to improve in
patients with preoperative LVEF of less than 0.35 (p = 0.014). There were no
significant differences in survival (p = 0.41), rehospitalization (p = 0.472),
and New York Heart Association Functional Classification (p = 0.307) among the
groups. The use of the smallest available sheath (18F) was not associated with a
significant change of DeltaEF. CONCLUSIONS: LVEF worsened in a small number of
patients after transapical transcatheter aortic valve implantation, but this
change was not associated with worse postoperative outcomes. Patients with a low
LVEF showed better improvement. The progressive reduction of sheath diameter does
not have a significant effect on LVEF changes.
PMID- 27614738
TI - Association of the MTHFR Gene C677T Polymorphism with Breast Cancer in a Turkish
Population.
AB - BACKGROUND: Breast cancer is the most common cancer among women. 1 in every 8
women in the United States have a lifetime risk of getting breast cancer. MTHFR
is a key enzyme that regulates the folate metabolism which has an important role
in DNA synthesis, repair, and methylation. The aim of the current study was to
analyze the association between the MTHFR gene C677T (Ala222Val, rs1801133)
polymorphism and breast cancer. PATIENTS AND METHODS: 199 breast cancer patients
and 195 healthy controls were included in this study. The MTHFR gene C677T
polymorphism was analyzed using polymerase chain reaction restriction fragment
length polymorphism (PCR-RFLP) methods. A meta-analysis including 707 breast
cancer patients and 880 controls from Turkish populations was also carried out.
Statistical analyses were performed using the chi2 test. RESULTS: No
statistically significant differences in allele and genotype frequencies were
observed between patients and controls (p > 0.05). Although not statistically
significant, TT homozygous variants were encountered more frequently in patients
than in controls. A statistically significant association was observed between
the MTHFR gene C677T polymorphism and the tumor histology of breast cancer
patients (p = 0.038). The results of the meta-analysis suggested that there was a
high association between breast cancer and the MTHFR gene C677T polymorphism in
Turkish populations (p < 0.0001). CONCLUSION: In our study, we did not find any
association between the MTHFR gene C677T polymorphism and breast cancer. However,
a meta-analysis of the 6 association studies carried out in Turkish populations
with 707 patients and 880 controls showed a significant association between
breast cancer and the MTHFR gene C677T polymorphism.
PMID- 27614739
TI - Diagnostic and Prognostic Value of Serum MicroRNA-206 in Patients with Gastric
Cancer.
AB - AIMS: Recent studies have demonstrated that microRNAs (miRNAs) can serve as
useful biomarkers for human cancers. The aim of this study was to evaluate the
expression level of serum miRNA-206 in patients with gastric cancer (GC) and
investigate its diagnostic and prognostic value. METHODS: Quantitative real-time
PCR was performed to evaluate serum miRNA-206 levels in 150 GC patients and 150
healthy volunteers. The association between miRNA-206 expression and
clinicopathological factors as well as patient's survival was analyzed. Receiver
operator curve (ROC) analysis was carried out to assess the potential value of
serum miRNA-206 for GC diagnosis. RESULTS: Serum miRNA-206 was down-regulated in
GC patients compared with healthy controls (P < 0.001). Decreased serum miRNA-206
expression was significantly associated with deep local invasion, positive lymph
node metastasis, and advanced clinical stage. Serum miRNA-206 expression was
found to be significantly up-regulated in paired post-operative samples and
reduced in patients with GC recurrence. ROC curve analysis showed that serum
miRNA-206 was a useful marker for GC diagnosis, and could discriminate between
recurred and non-recurred patients. Multivariate Cox regression analysis
confirmed low serum miRNA-206 expression as an independent unfavorable prognostic
factor for both DFS and OS of GC patients. CONCLUSIONS: These results suggest
that serum miRNA-206 might not only serve as a novel diagnostic biomarker for GC,
but also predict cancer recurrence and patient's prognosis.
PMID- 27614740
TI - Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.
AB - Neoadjuvant chemotherapy is indicated in patients who can tolerate the side
effects of a chemotherapy and with preoperative presentation of one of the
following clinical risk situations: bulky disease with a maximal tumor diameter
of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed
tomography (CT) scan or endosonography, histopathologically confirmed lymph node
metastasis, or histopathologically documented risk factors such as G3 and L1V1. A
neoadjuvant chemotherapy followed by surgery should be performed with cisplatin
at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The
previously published data suggests an improved rate of complete resection and
reduced incidences of positive lymph nodes and parametric infiltration.
Accordingly, the percentage of patients in need for adjuvant radiochemotherapy
after operation can be significantly reduced. Some studies demonstrated a
prolongation of progression-free and overall survival. Following the previously
published studies, adjuvant chemotherapy after operation or after
radiochemotherapy has no significant effect on the overall survival and,
following the current guidelines, should be avoided.
PMID- 27614741
TI - Therapierelevante Daten zu gastrointestinalen Tumoren beim ASCO 2016.
PMID- 27614742
TI - Uptake route and resulting toxicity of silver nanoparticles in Eisenia fetida
earthworm exposed through Standard OECD Tests.
AB - Despite the increasing interest in silver nanoparticles toxicity still few works
dealt with the hazards of nanosized Ag in soils (either dissolved in pore water
or coupled to colloids) although disposal of biosolids in landfills has been
reported as the major source of silver nanoparticles in terrestrial environments.
Presently, Eisenia fetida was used to assess the toxicity of 5 nm sized PVP-PEI
coated silver nanoparticles in soil through the implementation of different
exposure media Standard Toxicity Tests (Paper Contact and Artificial Soil -OECD
207- and Reproduction -OECD-222- Tests) together with cellular biomarkers
measured in extruded coelomocytes. In order to decipher the mode of action of
silver nanoparticles in soil and the uptake routes in earthworms, special
attention was given to the Ag accumulation and distribution in tissues. High Ag
accumulation rates, weight loss, and mortality due to the disruption of the
tegument could be the result of a dermal absorption of Ag ions released from
silver nanoparticles (Paper Contact Test). However, autometallography showed
metals mainly localized in the digestive tract after Artificial Soil Test,
suggesting that Ag uptake occurred mostly through soil ingestion. That is, silver
nanoparticles attached to soil colloids seemed to be internalized in earthworms
after ingestion of soil and transferred to the digestive gut epithelium where at
high doses they have triggered severe effects at different levels of biological
complexity.
PMID- 27614743
TI - Clarithromycin attenuates the expression of monocyte chemoattractant protein-1 by
activating toll-like receptor 4 in human mesangial cells.
AB - BACKGROUND: Signaling pathways induced by the activation of renal toll-like
receptor 4 (TLR4) play a pivotal role in chronic kidney disease (CKD). Some
recent studies suggested that clarithromycin (CAM), a 14-membered ring macrolide,
exerts renoprotective effects by suppressing proinflammatory chemokines. However,
its beneficial effects on signaling pathways through renal TLR4 activation are
unknown. METHODS: Cultured human mesangial cells (MCs) were treated with
lipopolysaccharide (LPS). Expression of monocyte chemoattractant protein-1 (MCP
1/CCL2) and interleukin-8 (IL-8/CXCL8) was analyzed by quantitative RT-PCR and
enzyme-linked immunosorbent assay. Signaling pathways affected by CAM were
determined by examining the activation of nuclear factor-kappaB (NF-kappaB) and
p38 mitogen-activated protein kinase (MAPK) by performing western blotting.
RESULTS: CAM inhibited both the mRNA and protein expression of MCP-1 without cell
injury but did not affect those expressions of IL-8 in LPS-stimulated MCs.
Interestingly, CAM decreased p38 MAPK activation by inhibiting phosphorylation
but did not affect NF-kappaB activation. CONCLUSION: Our results indicated that
CAM exerted renoprotective effects by suppression of p38 MAPK activity and by
decreasing the expression of MCP-1 in LPS-stimulated MCs. Given the implication
of TLR4 signaling in CKD, CAM may be a potential treatment of choice for CKD.
PMID- 27614746
TI - Preterm delivery and future maternal risk of female malignancies.
AB - PURPOSE: To investigate whether an association exists between preterm delivery
and a future risk for female malignancies. METHODS: A population-based study
compared the incidence of long-term female malignancies in a cohort of women with
and without a history of PTD. Deliveries occurred between the years 1988-2013,
with a mean follow-up duration of 12 years. We excluded women with known genetic
predisposition or malignancies prior to the index pregnancy. Malignancies
investigated included ovarian, uterine, breast and cervix. Cumulative incidence
was assessed using a Kaplan-Meier survival curve. A Cox proportional hazards
model was used to estimate the adjusted hazard ratios (HR) for female malignancy.
RESULTS: During the study period, 105,033 women met the inclusion criteria; 16.8
% (n = 17,596) of the patients delivered preterm. Patients with a history of PTD
did not have an increased risk of later being diagnosed with female malignancies.
The results remained insignificant in a sub-analysis based on malignancy type,
early PTD, induced vs. spontaneous, and number of episodes per patient. Kaplan
Meier cumulative incidence was similar between the groups, and the adjusted HR
was not significant (1.04, 95 % CI 0.88-1.22; p = 0.665). CONCLUSION: A history
of PTD does not appear to elevate the risk for subsequent long-term female
malignancies.
PMID- 27614744
TI - A Novel Combination of C-Reactive Protein and Vascular Endothelial Growth Factor
in Differential Diagnosis of Ascites.
AB - BACKGROUND AND AIMS: Ascites with unknown cause remains a diagnostic challenge,
which needs novel noninvasive biomarkers for the precise diagnosis. We aimed to
evaluate the ascitic fluid and serum C-reactive protein (CRP) and vascular
endothelial growth factor (VEGF) as diagnostic markers in the differential
diagnosis of malignant and benign ascites. METHODS: In this prospective work, 315
consecutive patients with ascites were studied. Ascitic fluid and serum levels of
CRP and VEGF were evaluated by using an enzyme-linked immunosorbent assay.
RESULTS: Patients were divided into a benign ascites group (group 1) (n = 256)
and a malignant ascites group (group 2) (n = 59). Ascitic and serum CRP were
significantly elevated in malignant ascites than benign ascites group [5.08 (3.62
6.58) vs. 1.82 (0.64-3.86) ng/ml; P < 0.001 and 12.7 (8.55-17.05) vs. 5.94 (2.57
10.64) ng/ml; P < 0.001], respectively. Ascitic and serum VEGF were significantly
increased in malignant ascites than benign ascites patients [0.68 (0.39-0.96) vs.
0.41 (0.25-0.83) ng/ml; P < 0.001 and 0.74 (0.41-1.08) vs. 0.54 (0.23-0.86)
ng/ml; P < 0.001], respectively. At a cutoff value of 7.3 and 0.63 ng/ml, serum
CRP and VEGF had specificity (77.3 and 89.5 %) and sensitivity (83.1 and 94.9 %)
for detecting malignant ascites [area under the curve (AUC) 0.821, 0.921],
respectively. At a cutoff value of 2.5 and 0.57 ng/ml, ascitic CRP and VEGF had
specificity (81.6 and 85.5 %) and sensitivity (84.7 and 91.5 %) for detecting
malignant ascites (AUC 0.842, 0.894), respectively. CONCLUSION: Elevated ascitic
fluid and serum CRP and VEGF values were related to the malignant ascites.
PMID- 27614745
TI - BRUCE Protein, New Marker for Targeted Therapy of Gastric Carcinoma.
AB - PURPOSE: Evading apoptosis is one of the major hallmarks of cancer cells.
Inhibitors of apoptosis (IAPs) proteins are considered as a most important gene
families involved in apoptosis. BRUCE protein, a member of IAPs, is able to
quench apoptosis as well as playing role in cell division. Our aim in this study
was to analyze BRUCE protein expression in gastric carcinoma (GC) and its
correlation with the clinicopathological features. METHODS: Using
immunohistochemistry, 52 GC specimens were studied for BRUCE protein expression.
A validated scoring method was applied. RESULTS: BRUCE protein expression was
detected in majority of tumor tissues (98.07 %). A significant correlation
between gender and BRUCE expression (p = 0.024) was detected. Indeed, females
showed higher level of BRUCE expression than male patients. CONCLUSION: Since
specific expression of BRUCE protein was revealed in majority of GC tissues,
BRUCE protein may be a useful therapeutic target for cancer therapy. Furthermore,
based on the native role of BRUCE protein in inhibition of apoptosis, using this
protein in targeted therapy of tumor cells may help to inhibit tumor cells growth
and survival leading to rapid elimination of tumor mass.
PMID- 27614747
TI - An association between fine particulate matter (PM2.5) levels and emergency
ambulance dispatches for cardiovascular diseases in Japan.
AB - PURPOSE: The aim of this study is to determine whether short-term exposure to
fine particulate matter (PM2.5) is associated with emergency ambulance dispatches
for cardiovascular diseases in Japan. METHODS: The nationwide data on emergency
dispatches of ambulance for cardiovascular diseases classified as I00-I99 by
International Classification of Diseases-10th revision in 30 Japanese prefectures
between April 1 and December 31, in 2010 were analyzed. Data on weather
variability including PM2.5, temperature and relative humidity were acquired from
ambient air pollution monitoring stations. Conditional Poisson regression models
were used to estimate the prefecture-specific effects of PM2.5 on morbidity, and
adjust for confounding factors. A meta-analysis was then applied to pool
estimates at the 30-prefecture level. RESULTS: A total of 160,566 emergency
ambulance dispatches for cardiovascular diseases were reported during the study
period. The risk of emergency ambulance dispatch for cardiovascular diseases
significantly increased with an increase in the exposure to PM2.5 in Fukuoka and
Iwate Prefectures. However, we found no statistically significant associations
between PM2.5 and emergency ambulance dispatches in the pooled analysis (odds
ratio 1.00, 95 % confidence interval 0.99-1.00). Heterogeneity was not observed
between prefectures (Cochran Q test, p = 0.187, I 2 = 18.4 %). CONCLUSIONS:
Exposure to PM2.5 is not associated with overall emergency ambulance dispatches
for cardiovascular diseases in Japan.
PMID- 27614748
TI - Antimicrobial binding and growth kinetics in BacT/ALERT(r) FA Plus and BACTEC(r)
Aerobic/F Plus blood culture media.
AB - The capacity of absorbent beads in BacT/ALERT(r) FA Plus and BACTEC(r) Aerobic/F
Plus blood culture bottles to bind and neutralize antibiotics was compared.
Binding was established using reverse-phase HPLC, and inactivation was based on
the recovery of susceptible test stains from simulated blood cultures. The FA
Plus medium demonstrated more rapid and better overall binding kinetics for each
drug tested, resulting in significantly better overall recovery rates.
Differences in time to detection favored the FA Plus medium for three
drug/organism combinations and Aerobic/F Plus for two.
PMID- 27614751
TI - Identification of zebrafish magnetoreceptor and cryptochrome homologs.
AB - Magnetoreception is essential for magnetic orientation in animal migration. The
molecular basis for magnetoreception has recently been elucidated in fruitfly as
complexes between the magnetic receptor magnetoreceptor (MagR) and its ligand
cryptochrome (Cry). MagR and Cry are present in the animal kingdom. However, it
is unknown whether they perform a conserved role in diverse animals. Here we
report the identification and expression of zebrafish MagR and Cry homologs
towards understanding their roles in lower vertebrates. A single magr gene and 7
cry genes are present in the zebrafish genome. Zebrafish has four cry1 genes
(cry1aa, cry1ab, cry1ba and cry1bb) homologous to human CRY1 and a single
ortholog of human CRY2 as well as 2 cry-like genes (cry4 and cry5). By RT-PCR,
magr exhibited a high level of ubiquitous RNA expression in embryos and adult
organs, whereas cry genes displayed differential embryonic and adult expression.
Importantly, magr depletion did not produce apparent abnormalities in
organogenesis. Taken together, magr and cry2 exist as a single copy gene, whereas
cry1 exists as multiple gene duplicates in zebrafish. Our result suggests that
magr may play a dispensable role in organogenesis and predicts a possibility to
generate magr mutants for analyzing its role in zebrafish.
PMID- 27614750
TI - Association of p53 codon 72 polymorphism and survival of North Indian lung cancer
patients treated with platinum-based chemotherapy.
AB - p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA
repair or cellular apoptosis during DNA damage. So, as to find the association of
p53Arg 72 Pro towards lung carcinogenesis and overall survival of North Indian
lung cancer patients, single nucleotide polymorphic variant (rs1042522) was
analyzed. 840 subjects including 420 cases and 420 controls were recruited and
genotyped using PCR-RFLP technique for p53Arg 72 Pro polymorphic site.
Association was analyzed using adjusted odds ratio along with its confidence
intervals (95 % CI) and p value predicted from logistic regression whereas
overall survival for lung cancer patients was obtained using Kaplan-Meir and Cox
regression model for different parameters to obtain hazard ratio and survival
time with statistical significance (log-rank p value). None of the variant
genotypes for p53Arg 72 Pro showed any association towards lung cancer risk or
any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had
better median survival time as compared to Arg/Pro genotype (10 months; HR =
0.65; 95 % CI = 0.45-0.95; p = 0.03). Furthermore, female lung cancer patients
with Arg/Pro (HR = 0.08; 95 % CI = 0.02-0.34; p = 0.0005) and Pro/Pro (HR = 0.21;
95 % CI = 0.06-0.67; p = 0.008) genotypes showed a better overall survival and
hence a better prognosis as compared to males. Our data also reveals that lung
cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had
better chances of survival. p53 codon 72 polymorphism could play a role as a
prognostic marker in lung cancer patients.
PMID- 27614749
TI - Pharmacological Potential of Phylogenetically Diverse Actinobacteria Isolated
from Deep-Sea Coral Ecosystems of the Submarine Aviles Canyon in the Cantabrian
Sea.
AB - Marine Actinobacteria are emerging as an unexplored source for natural product
discovery. Eighty-seven deep-sea coral reef invertebrates were collected during
an oceanographic expedition at the submarine Aviles Canyon (Asturias, Spain) in a
range of 1500 to 4700 m depth. From these, 18 cultivable bioactive Actinobacteria
were isolated, mainly from corals, phylum Cnidaria, and some specimens of phyla
Echinodermata, Porifera, Annelida, Arthropoda, Mollusca and Sipuncula. As
determined by 16S rRNA sequencing and phylogenetic analyses, all isolates belong
to the phylum Actinobacteria, mainly to the Streptomyces genus and also to
Micromonospora, Pseudonocardia and Myceligenerans. Production of bioactive
compounds of pharmacological interest was investigated by high-performance liquid
chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) techniques
and subsequent database comparison. Results reveal that deep-sea isolated
Actinobacteria display a wide repertoire of secondary metabolite production with
a high chemical diversity. Most identified products (both diffusible and
volatiles) are known by their contrasted antibiotic or antitumor activities.
Bioassays with ethyl acetate extracts from isolates displayed strong antibiotic
activities against a panel of important resistant clinical pathogens, including
Gram-positive and Gram-negative bacteria, as well as fungi, all of them isolated
at two main hospitals (HUCA and Cabuenes) from the same geographical region. The
identity of the active extracts components of these producing Actinobacteria is
currently being investigated, given its potential for the discovery of
pharmaceuticals and other products of biotechnological interest.
PMID- 27614752
TI - Non-integrating lentiviral vectors based on the minimal S/MAR sequence retain
transgene expression in dividing cells.
AB - Safe and efficient gene transfer systems are the basis of gene therapy
applications. Non-integrating lentiviral (NIL) vectors are among the most
promising candidates for gene transfer tools, because they exhibit high transfer
efficiency in both dividing and non-dividing cells and do not present a risk of
insertional mutagenesis. However, non-integrating lentiviral vectors cannot
introduce stable exogenous gene expression to dividing cells, thereby limiting
their application. Here, we report the design of a non-integrating lentiviral
vector that contains the minimal scaffold/matrix attachment region (S/MAR)
sequence (SNIL), and this SNIL vector is able to retain episomal transgene
expression in dividing cells. Using SNIL vectors, we detected the expression of
the eGFP gene for 61 days in SNIL-transduced stable CHO cells, either with
selection or not. In the NIL group without the S/MAR sequence, however, the
transduced cells died under selection for the transient expression of NIL
vectors. Furthermore, Southern blot assays demonstrated that the SNIL vectors
were retained extrachromosomally in the CHO cells. In conclusion, the minimal
S/MAR sequence retained the non-integrating lentiviral vectors in dividing cells,
which indicates that SNIL vectors have the potential for use as a gene transfer
tool.
PMID- 27614753
TI - The complete sequence and genome organization of ligustrum virus A, a novel
carlavirus.
AB - The complete genome sequence of ligustrum virus A (LVA) from a Ligustrum
obtusifolium Sieb. & Zucc. plant was determined. The genomic RNA has 8,525
nucleotides, excluding the poly(A) tail, and consists of six open reading frames
typical of members of the genus Carlavirus, family Betaflexiviridae. Phylogenetic
analysis of the viral replicase and coat protein (CP) indicated that LVA is
closely related to daphne virus S and helenium virus. The replicase and CP of LVA
shared 44.73-52.35 % and 25.39-62.46 % amino acid identity, respectively, with
those of other carlaviruses. These results suggest that LVA is a member of a
distinct carlavirus species.
PMID- 27614754
TI - Residual FDG uptake of primary thyroid lymphoma after treatment may overestimate
residual lymphoma.
AB - OBJECTIVE: To assess 18F-fluorodeoxyglucose positron emission tomography/computed
tomography (18F-FDG PET/CT) images in primary thyroid lymphoma (PTL) patients
before and after treatment. METHODS: We conducted a retrospective review of data
for ten patients (four men, six women) of mean age 65 (range 48-88) years, with
histopathologically confirmed malignant thyroid lymphoma who underwent pre
treatment and post-treatment 18F-FDG PET between January 2005 and December 2014.
Thyroid uptake was assessed by the 5-point scale score based on maximum intensity
projection images. RESULTS: Four of the ten patients were judged to have a
complete metabolic response (scores 1-3) and four to have a partial metabolic
response (PMR; scores 4-5). Three of the four PMR patients had a good outcome
with a treatment-free interval and overall survival of at least 53.0 months,
although two of these three patients showed residual FDG uptake in the thyroid
for more than 2 years after completion of treatment. Two of the ten patients were
considered to have progressive metabolic disease. CONCLUSIONS: In patients with
PTL, residual FDG uptake in the thyroid after treatment that corresponds to a PMR
may not always indicate a poor outcome.
PMID- 27614756
TI - Effects of novel oral anticoagulants on left atrial and left atrial appendage
thrombi: an appraisal.
AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and
predisposes to an increased risk of thromboembolic events. Patients affected by
AF exhibit an increased risk of stroke compared with those in sinus rhythm, with
the most common location of thrombi in the left atrial appendage. Until 2009,
warfarin and other vitamin K antagonists were the only class of oral
anticoagulants available. More recently, dabigatran, rivaroxaban, apixaban, and
edoxaban have been approved by regulatory authorities for prevention of stroke in
patients with non-valvular AF. Few data are available about the efficacy of novel
oral anticoagulants for the treatment of left atrial and left atrial appendage
thrombosis. Aim of this review is to summarize available evidence regarding the
effectiveness of novel oral anticoagulants on left atrial appendage thrombosis.
PMID- 27614757
TI - Thrombocytopenia in hospitalized patients with severe clostridium difficile
infection.
AB - Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea
and colitis. The incidence and prognostic significance of thrombocytopenia as
related to mode of acquisition (hospital vs. community), NAP1/027 strain, and
disease severity has not been examined. We performed a single-institution
retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with
CDI during their hospitalization to document the incidence/prevalence of
thrombocytopenia and associated outcomes. Severe disease was defined by a
composite endpoint of inpatient death, death within 30 days of discharge,
presence of septic shock, or need for colectomy during hospitalization. Of the
533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 *
109/L at time of CDI diagnosis) was present in 15 % of the total cohort and
incident thrombocytopenia developed in 3 % of patients after admission.
Thrombocytopenia was more common in hospital-acquired disease and associated with
increased length of stay, but was not associated with treatment failure. Those
with moderate thrombocytopenia were more likely to have severe disease, after
controlling for white blood cell count, albumin, and creatinine. Moderate
thrombocytopenia is associated with poor prognosis and is a potential risk
stratification tool for severe CDI.
PMID- 27614758
TI - Laparoscopic fixation of the vaginal cuff to the uterosacral ligaments at the
time of hysterectomy.
AB - INTRODUCTION AND HYPOTHESIS: Transvaginal ipsilateral uterosacral ligament
colpopexy for pelvic organ prolapse (POP), which was reported by Shull et al.
(Shull's colpopexy) in 2000, is one of the most frequently performed non-mesh
pelvic floor reconstructive surgical procedures. Despite its excellent anatomical
outcomes, ureteral injury and difficulty in uterosacral ligament detection
(especially in patients with severe POP) are typical issues with this procedure.
METHOD: This video demonstrates the procedure in a 58-year-old woman, gravida 2
para 2, with POP-Q stage II uterine prolapse and stage I cystocele. At the
beginning of the operation, the bilateral uterosacral ligaments were confirmed
and separated from the ureters after entering the retroperitoneal space. The
inferior hypogastric nerve and pelvic nerve plexus were also separated from the
uterosacral ligament. After total laparoscopic hysterectomy, three ipsilateral
delayed absorbable monofilament sutures were placed between the uterosacral
ligament and the vaginal cuff. Retroperitonealization was then performed using a
continuous suture with closure of the Douglas pouch. CONCLUSION: Laparoscopic
Shull's colpopexy for POP is a secure procedure with the advantages of
laparoscopy (magnification and sharing the operative field). This may become one
of the most useful operations for apical support as native tissue repair.
PMID- 27614755
TI - Salt Sensitivity: Challenging and Controversial Phenotype of Primary
Hypertension.
AB - Increases in life expectancy and cardiovascular adverse events in patients with
hypertension highlight the need for new risk-reduction strategies to reduce the
burden of degenerative diseases. Among the environmental factors, high salt
consumption is currently considered the most important risk factor of
hypertension. However, while high salt intake significantly raises blood pressure
in some individuals, others do not show variation or even decrease their blood
pressure. This heterogeneity is respectively classified as salt sensitivity and
salt resistance. In this review, we propose salt sensitivity as a useful
phenotype to unravel the mechanistic complexity of primary hypertension. The
individual variability in blood pressure modification in response to salt intake
changes derives from the combination of genetic and environmental determinants.
This combination of random and non random determinants leads to the development
of a personal index of sensitivity to salt. However, those genes involved in
susceptibility to salt are still not completely identified, and the triggering
mechanisms underlying the following development of hypertension still remain
uncovered. One reason might be represented by the absence of a specific protocol,
universally followed, for a standard definition of salt sensitivity. Another
reason may be linked to the absence of common criteria for patient recruitment
during clinical studies. Thus, the generation of a reliable approach for a proper
recognition of this personal index of sensitivity to salt, and through it the
identification of novel therapeutic targets for primary hypertension, should be
one of the aspirations for the scientific community.
PMID- 27614759
TI - Intravesical treatment for interstitial cystitis/painful bladder syndrome: a
network meta-analysis.
AB - INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/painful bladder syndrome
(IC/PBS) is a chronic inflammatory condition of the submucosal and muscular
layers of the bladder. So far, there is no effective and targeted treatment
strategy for IC/PBS. This study aimed to assess the efficacy and safety of
intravesical instillation treatment in IC/PBS patients. METHODS: We searched
various databases up to October 2015. A network meta-analysis was performed to
compare global response assessment (GRA) for different treatment strategies,
including botulinum toxin A (BoNTA), bacillus Calmette-Guerin (BCG),
resiniferatoxin (RTX), lidocaine, chondroitin sulfate (CS), oxybutynin, and
pentosan polysulfate (PPS). A traditional meta-analysis was also performed.
RESULTS: Sixteen trials evaluating 905 patients were included. Network meta
analysis indicated that BoNTA had the highest probability of being the best
treatment course according to GRA assessment results (probability 81.7 %). BCG or
BoNTA therapy yielded significant improvement in GRA incidence according to
traditional meta-analysis. Patients who received PPS showed higher urinary
frequency results compared with the placebo groups. BCG- and PPS-treated patients
had elevated urinary urgency treatment effects compared with placebo groups.
Bladder capacity restoration results also showed significant improvements in
patients who received BoNTA compared with placebo-treated individuals.
CONCLUSIONS: These findings indicate that BoNTA therapy has the highest
probability of being the best therapy according to GRA, and significantly
improves bladder capacity in IC/PBS patients. BCG treatment also significantly
increases the incidence of GRA and improves the symptoms of urinary urgency. PPS
can significantly improve urinary frequency and urgency symptoms in IC/PBS
patients.
PMID- 27614760
TI - Reply letter to the editor, regarding the role of radical surgery in the
management of CEAP C5/6 and lipodermatosclerosis.
PMID- 27614761
TI - A novel computational remodelling algorithm for the probabilistic evolution of
collagen fibre dispersion in biaxially strained vascular tissue.
AB - In this work, we constructed a novel collagen fibre remodelling algorithm that
incorporates the complex nature of random evolution acting on single fibres
causing macroscopic fibre dispersion. The proposed framework is different from
the existing remodelling algorithms, in that the microscopic random force on
cellular scales causing a rotational-type Brownian motion alone is considered as
an aspect of vascular tissue remodelling. A continuum mechanical framework for
the evolution of local dispersion and how it could be used for modeling the
evolution of internal radius of biaxially strained artery structures under
constant internal blood pressure are presented. A linear evolution form for the
statistical fibre dispersion is employed in the model. The random force component
of the evolution, which depends on the mechanical stress stimuli, is described by
a single parameter. Although the mathematical form of the proposed model is
simple, there is a strong link between the microscopic evolution of collagen
dispersion on the cellular level and its effects on the macroscopic visible world
through mechanical variables. We believe that the proposed algorithm utilizes a
better understanding of the relationship between the evolution rates of mean
fibre direction and fibre dispersion. The predictive capability of the algorithm
is presented using experimental data. The model has been simulated by solving a
single-layered axisymmetric artery (adventitia) deformation problem. The
algorithm performed well for estimating the quantitative features of experimental
anisotropy, the mean fibre direction vector and the dispersion (kappa)
measurements under strain-dependent evolution assumptions.
PMID- 27614763
TI - Novel Piperazino-Enaminones Suppress Pro-Inflammatory Cytokines and Inhibit
Chemokine Receptor CCR2.
AB - Pro-inflammatory mediators including TNF-alpha, IL-6, and nitric oxide are
important for the regulation of the immune response when an infection is present,
but when overproduced, it can be responsible for the development of tissue and
organ injury seen in sepsis, as well as severe asthma, and autoimmune diseases
such as Crohn's disease and rheumatoid arthritis. Data from our lab to
characterize the novel compound enaminone E121 have suggested that macrophages
stimulated with lipopolysaccharide (LPS) release significantly decreased levels
of TNF-alpha and IL-6 as measured by enzyme-linked immunosorbent assay as
compared to the DMSO control group. Additionally, functional experiments in a
mouse model of asthma have shown that E121 is efficacious in decreasing airway
hyperresponsiveness. A new set of compounds synthesized in our lab (JODI) have an
N-aryl piperazino motif incorporated on the aromatic side of the enaminone
pharmacophore. It was hypothesized that this would enhance their
immunosuppressive activity as anti-inflammatory agents by also acting as a
chemokine receptor antagonist. Our studies suggest that JODI appears to suppress
TNF-alpha and IL-6 in a dose-dependent manner. The JODI compounds were also more
effective in reducing TNF-alpha after LPS stimulation when compared to
dexamethasone. Lastly, studies using MCP-1 suggest that the JODI compounds, and
not E121, are able to block CCR2 signaling as evidenced by decreased total
ERK1/2. These studies indicate that E121 and its corresponding piperazino analogs
could act as strong anti-inflammatory agents in asthma or other autoimmunities
where efficacious therapeutic options are needed.
PMID- 27614764
TI - Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic
Rhinosinusitis with Nasal Polyps.
AB - The pathophysiologic mechanisms of human chronic rhinosinusitis with nasal polyps
(CRSwNP) remain unclear. We aimed to elucidate expression and biologic role of
NLRP3 inflammasome in CRSwNP. Immunohistochemistry (IHC) was conducted to assess
NLRP3 immunolabeling, real-time polymerase chain reaction (PCR) was used for IL-9
and NLRP3, and caspase-1 level quantitation in CRSwNP and control subjects. In
addition, enzyme-linked immunosorbent assay (ELISA) was employed for analyzing
concentrations of IL-1beta and IL-18 in the homogenates prepared from tissue
specimens. Moreover, human nasal epithelial cells (HNECs) were used to evaluate
the effects of lipopolysaccharide (LPS) and glyburide on NLRP3 inflammasome
signaling pathway. Results showed that NLRP3 and caspase-1 were overexpressed in
CRSwNP, especially in eosinophilic CRSwNP (ECRSwNP). Interestingly, NLRP3
expression had close correlation to that of caspase-1. Concentrations of IL-1beta
and IL-18 were elevated. NLRP3 inflammasome signaling pathway was augmented by
LPS but suppressed by glyburide. In conclusion, NLRP3 inflammasome signaling
pathway played a pro-inflammatory role in the pathogenesis of CRSwNP, especially
in ECRSwNP. NLRP3 inflammasome signaling pathway was augmented by LPS, but
suppressed by glyburide.
PMID- 27614765
TI - Bringing analysis of gender and social-ecological resilience together in small
scale fisheries research: Challenges and opportunities.
AB - The demand for gender analysis is now increasingly orthodox in natural resource
programming, including that for small-scale fisheries. Whilst the analysis of
social-ecological resilience has made valuable contributions to integrating
social dimensions into research and policy-making on natural resource management,
it has so far demonstrated limited success in effectively integrating
considerations of gender equity. This paper reviews the challenges in, and
opportunities for, bringing a gender analysis together with social-ecological
resilience analysis in the context of small-scale fisheries research in
developing countries. We conclude that rather than searching for a single
unifying framework for gender and resilience analysis, it will be more effective
to pursue a plural solution in which closer engagement is fostered between
analysis of gender and social-ecological resilience whilst preserving the
strengths of each approach. This approach can make an important contribution to
developing a better evidence base for small-scale fisheries management and
policy.
PMID- 27614766
TI - Comparing the mechanical strength of hip spica cast between a conventional and a
new method of application.
AB - PURPOSE: The current technique of hip spica application is mostly based on a
publication by Kumar (J Pediatr Orthop 1(1):97-99, 1981). We modified the
technique of hip spica application in order to reduce the rate of breakage across
the hip joint and designed this study to compare the strength between hip spica
applied according to Kumar's technique and the new technique. METHODS: We created
12 hip spica casts with 24 hips according to Kumar's technique, and another 12
casts according to a new technique. The two types of spica were tested with a
mechanical testing machine (Instron 3365 series) by using compression loading to
failure in flexion, extension, abduction and adduction. Data were analysed in
SPSS version 20.0. Comparison of means was done with an independent T test for
normally distributed data and the Mann-Whitney test for skewed data. RESULTS: The
new technique involved the creation of three slabs, instead of 14 slabs as
described by Kumar. The loads to failure for hip spica cast applied according to
the new technique were higher than those applied according to Kumar's technique,
and the differences were statistically significant. The stiffness was also higher
in spica casts applied with the new technique; the difference was not
statistically significant under extension force. CONCLUSION: Hip spica applied
with the new technique was stronger than that applied according to Kumar's
technique based on load to failure testing. The new technique of application
would potentially reduce the risk of cast breakage during the management of
developmental dysplasia of the hip (DDH) and femur fracture in children.
PMID- 27614762
TI - Systematic review reveals lack of quality in reporting health-related quality of
life in patients with gastroenteropancreatic neuroendocrine tumours.
AB - BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NET) are often
slow-growing and patients may live for years with metastasised disease. Hence,
along with increasing overall and progression-free survival, treatments aim at
preserving patients' well-being and health-related quality of life (HRQoL).
However, studies on systematic HRQoL assessment in patients with GEP-NET are
scarce. Therefore, the purpose of the current review is to systematically
evaluate the methodological quality of the identified studies. METHODS: A
targeted database search was performed in PubMed, EMBASE, and CENTRAL. Data
extraction was conducted by two independent researchers according to predefined
criteria. For study evaluation, the Minimum Standard Checklist for Evaluating
HRQoL Outcomes in Cancer Clinical Trials and the CONSORT Patient-Reported Outcome
extension were adapted. RESULTS: The database search yielded 48 eligible studies.
We found the awareness for the need of HRQoL measurement to be growing and
application of cancer-specific instruments gaining acceptance. Overall, studies
were too heterogeneous in terms of patient characteristics and treatment
interventions to draw clear conclusions for clinical practice. More importantly,
a range of methodological shortcomings has been identified which were mainly
related to the assessment and statistical analysis, as well as the reporting and
interpretation of HRQoL data. CONCLUSION: Despite an increasing interest in HRQoL
in GEP-NET patients, there is still a lack of knowledge on this issue. A transfer
of HRQoL results into clinical practice is hindered not only by the scarceness of
studies, but also by the often limited quality of HRQoL processing and reporting.
PMID- 27614767
TI - Social Pavlovian conditioning: Short- and long-term effects and the role of
anxiety and depressive symptoms.
AB - Today's stressors largely arise from social interactions rather than from
physical threat. However, the dominant laboratory model of emotional learning
relies on physical stimuli (e.g. electric shock) whereas adequate models of
social conditioning are missing, possibly due to more subtle and multilayered
biobehavioral responses to such stimuli. To fill this gap, we acquired a broad
set of measures during conditioning to negative social unconditioned stimuli,
also taking into account long-term maintenance of conditioning and inter
individual differences. Fifty-nine healthy participants underwent a classical
conditioning task with videos of actors expressing disapproving (US-neg) or
neutral (US-neu) statements. Static images of the corresponding actors with a
neutral facial expression served as CS+ and CS-, predicting US-neg and US-neu,
respectively. Autonomic and facial-muscular measures confirmed differential
unconditioned responding whereas experiential CS ratings, event-related
potentials, and evoked theta oscillations confirmed differential conditioned
responding. Conditioning was maintained at 1 month and 1 year follow-ups on
experiential ratings, especially in individuals with elevated anxiety and
depressive symptoms, documenting the efficiency of social conditioning and its
clinical relevance. This novel, ecologically improved conditioning paradigm
uncovered a remarkably efficient multi-layered social learning mechanism that may
represent a risk factor for anxiety and depression.
PMID- 27614768
TI - The effect of social rank feedback on risk taking and associated reward processes
in adolescent girls.
AB - The onset of adolescence is associated with an increased tendency to engage in
risky behaviors and a developmental shift toward peers that contributes to
increased prioritization for learning about and achieving social status. There is
relatively little understanding about the specific links between these adolescent
typical phenomena, particularly regarding their neural underpinnings. Based on
existing models that suggest the role of puberty in promoting adolescent status
seeking and risk-taking tendencies, we investigated the relation of pubertal
hormones with behavioral and neural responses to status-relevant social
information in the context of risk taking. We used a probabilistic decision task
in which 11- to 13-year-old girls chose to take a risk, or not, while receiving
either social rank or monetary performance feedback. While feedback type did not
differentially influence risk-taking behavior, whole-brain imaging results showed
that activation in the anterior insula was increased for risk taking in the
social rank feedback condition compared to the monetary feedback condition. This
heightened activation was more pronounced in girls with higher estradiol levels.
These findings suggest that brain processes involved in adolescent risky
decisions may be influenced by the desire for social-status enhancement and
provide preliminary evidence for the role of pubertal hormones in enhancing this
adolescent-typical social sensitivity.
PMID- 27614769
TI - Intranasal oxytocin increases neural responses to social reward in post-traumatic
stress disorder.
AB - Therapeutic alliance and perceived social support are important predictors of
treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin
administration may enhance treatment response by increasing sensitivity for
social reward and thereby therapeutic alliance and perceived social support. As a
first step to investigate this therapeutical potential, we investigated whether
intranasal oxytocin enhances neural sensitivity to social reward in PTSD
patients. Male and female police officers with (n = 35) and without PTSD (n = 37)
were included in a double-blind, randomized, placebo-controlled cross-over fMRI
study. After intranasal oxytocin (40 IU) and placebo administration, a social
incentive delay task was conducted to investigate neural responses during social
reward and punishment anticipation and feedback. Under placebo, PTSD patients
showed reduced left anterior insula (AI) responses to social rewards (i.e. happy
faces) compared with controls. Oxytocin administration increased left AI
responses during social reward in PTSD patients, such that PTSD patients no
longer differed from controls under placebo. Furthermore, in PTSD patients,
oxytocin increased responses to social reward in the right putamen. By
normalizing abberant insula responses and increasing putamen responses to social
reward, oxytocin administration may enhance sensitivity for social support and
therapeutic alliance in PTSD patients. Future studies are needed to investigate
clinical effects of oxytocin.
PMID- 27614772
TI - Respiratory Surgery.
AB - This article is a review of the most frequent disorders affecting the upper
airway of cattle that are suitable for surgery. Information regarding the
clinical signs, diagnostic methods, and the chemical restraint of cattle in
respiratory distress are highlighted. Surgeries that can be performed in a field
setting are thoroughly described.
PMID- 27614771
TI - Avian axons undergo Wallerian degeneration after injury and stress.
AB - The integrity of long axons is essential for neural communication. Unfortunately,
relatively minor stress to a neuron can cause extensive loss of this integrity.
Axon degeneration is the cell-intrinsic program that actively deconstructs an
axon after injury or damage. Although ultrastructural examination has revealed
signs of axon degeneration in vivo, the occurrence and progression of axon
degeneration in avian species have not yet been documented in vitro. Here, we use
a novel cell culture system with primary embryonic zebra finch retinal ganglion
cells to interrogate the properties of avian axon degeneration. First, we
establish that both axotomy and a chemically induced injury (taxol and
vincristine) are sufficient to initiate degeneration. These events are dependent
on a late influx of calcium. In addition, as in mammals, the NAD pathway is
involved, since a decrease in NMN with FK866 can reduce degeneration.
Importantly, these retinal ganglion cell axons were sensitive to a pressure
induced injury, which may mimic the effect of high intraocular pressure
associated with glaucoma. We have demonstrated that avian neurons undergo
Wallerian degeneration in response to both physical and chemical injury.
Subsequent avian studies will investigate whether blocking the degeneration
pathway can protect individuals from neurodegenerative disease.
PMID- 27614773
TI - Surgery of the Umbilicus and Related Structures.
AB - Ruminants of all types requiring umbilical surgery can be affected by a number of
different conditions. However, the practitioner should be able to correct any of
these conditions surgically, especially in young animals, as a field procedure if
appropriate restraint and environment are available. Like other aspects of
veterinary practice, the individual must decide what services he or she wishes to
offer clients in their practice and which ones will be referred. The objective of
this article is to equip veterinarians who wish to treat umbilical masses
surgically with the information they need.
PMID- 27614770
TI - Pictures of disgusting foods and disgusted facial expressions suppress the tongue
motor cortex.
AB - The tongue holds a unique role in gustatory disgust. However, it is unclear
whether the tongue representation in the motor cortex (tM1) is affected by the
sight of distaste-related stimuli. Using transcranial magnetic stimulation (TMS)
in healthy humans, we recorded tongue motor-evoked potentials (MEPs) as an index
of tM1 cortico-hypoglossal excitability. MEPs were recorded while participants
viewed pictures associated with gustatory disgust and revulsion (i.e. rotten
foods and faces expressing distaste), non-oral-related disgusting stimuli (i.e.
invertebrates like worms) and control stimuli. We found that oral-related disgust
pictures suppressed tM1 cortico-hypoglossal output. This tM1 suppression was
predicted by interindividual differences in disgust sensitivity. No similar
suppression was found for disgusting invertebrates or when MEPs were recorded
from a control muscle. These findings suggest that revulsion-eliciting food
pictures trigger anticipatory inhibition mechanisms, possibly preventing toxin
swallowing and contamination. A similar suppression is elicited when viewing
distaste expressions, suggesting vicarious motor inhibition during social
perception of disgust. Our study suggests an avoidant-defensive mechanism in
human cortico-hypoglossal circuits and its 'resonant' activation in the vicarious
experience of others' distaste. These findings support a role for the motor
system in emotion-driven motor anticipation and social cognition.
PMID- 27614774
TI - Surgical Management of Fractures and Tendons.
AB - Long bone fractures and disorders of tendons and ligaments represent a
significant proportion of surgical orthopedic cases presented to ruminant
veterinarians. The presentation of these patients, their diagnostic work-up,
surgical treatment, and expected outcome will be discussed. The outcome of these
cases depends largely on the presenting problem; however, accurate diagnosis and
prompt surgical intervention can greatly improve the outcome of many of these
cases.
PMID- 27614775
TI - Surgical Management of Abomasal Disease.
AB - Abomasal diseases are common in cattle. Many of these diseases can be managed
surgically. This article briefly discusses the various surgical diseases
affecting the abomasum. The pathogenesis, surgical procedures, and prognosis are
reviewed. Abomasal displacements in cattle are a focus, because surgical
correction of these conditions represents the bulk of abomasal surgeries in
ruminants. Surgical principles of conventional surgery as well as minimally
invasive techniques for correction of abomasal displacements are discussed. The
surgical management of other abomasal diseases such as intraluminal abomasal
obstructions and abomasal ulcers are also reviewed.
PMID- 27614776
TI - Field Sedation and Anesthesia of Ruminants.
AB - Many surgical procedures on ruminants can be performed humanely and safely using
local or regional anesthesia and physical restraint, but sedation and general
anesthesia are necessary in order to perform some procedures. Although anesthesia
associated risks are greater in ruminants than monogastrics, ruminants can be
anesthetized relatively safely in a field setting if the risks are understood,
and adequate planning and precautions are in place. This article discusses the
important features impacting sedation and anesthesia of cattle and small
ruminants, and describes some commonly used drug protocols.
PMID- 27614777
TI - Intestinal Surgery.
AB - A wide variety of disorders affecting the intestinal tract in cattle may require
surgery. Among those disorders the more common are: intestinal volvulus, jejunal
hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus.
Although general principles of intestinal surgery can be applied, cattle has
anatomical and behavior particularities that must be known before invading the
abdomen. This article focuses on surgical techniques used to optimize outcomes
and discusses specific disorders of small intestine. Diagnoses and surgical
techniques presented can be applied in field conditions.
PMID- 27614778
TI - Effect of paranasal anatomical variants on outcomes in patients with limited and
diffuse chronic rhinosinusitis.
AB - OBJECTIVE: The role of anatomical variants of the paranasal sinuses in the
aetiology of chronic rhinosinusitis (CRS) is not well understood. Furthermore,
the effect of anatomical variants on long-term outcomes has not been described.
This study aims to assess the effects of anatomical variants of the middle meatus
on patients with limited and diffuse CRS. METHODS: A database analysis was
conducted for patients with limited sinusitis (undergoing anterior FESS) and
patients with diffuse sinusitis (undergoing complete FESS) between 2009 and 2013.
Intergroup comparisons were made for symptom scores, CT scans, revision surgery,
re-referrals following discharge and number of clinic follow-ups. RESULTS: A
total of 86 patients were included in the study: 40 anterior FESS, 25 CRSwNP and
21 CRSsNP. Following surgery, anterior FESS symptom scores reduced by 4.6+/-0.8
on average, while the CRSwNP and CRSsNP group reduced by 5.7+/-1.1 and 5.9+/-1.3
respectively. Patients undergoing anterior FESS required fewer clinic follow-ups
than CRSwNP (Delta 2.7+/-0.9, P<0.001) and CRSsNP (Delta 3.3+/-0.6, P<0.001).
Patients with fewer anatomical variants (0-2) required more follow-up (5.2+/-0.6)
than those with higher numbers of variants (3+) (3.8+/-0.3, P=0.05). No
significant differences were seen between groups for revision surgery, repeat CT
and re-referral rates. CONCLUSION: Limited surgery for local disease demonstrated
comparable symptom improvement to patients with extensive disease receiving
extensive surgery. Patients with greater numbers of anatomical variants are
associated with localised sinus disease who typically require less postoperative
care after receiving limited surgery.
PMID- 27614779
TI - Zebrafish as a novel model for non-typhoidal Salmonella pathogenesis,
transmission and vaccine efficacy.
AB - Salmonella-induced gastroenteritis causes massive morbidity and mortality in both
adults and children of developing countries. However, it is difficult to study
the mode of infection and vaccine efficacy due to inadequacies of current animal
models. For this reason, we have explored using zebrafish as an improved model
for non-typhoidal Salmonella (NTS) infection, including Salmonella enterica
Typhimurium, Salmonella enterica Enteritidis and Salmonella enterica Weltevreden.
In this study, we found that after infection of zebrafish with NTS, severe
diarrhea like symptoms were observed and NTS significantly colonized the
zebrafish intestine without any manipulation of the normal intestinal microbiota
of the fish. Furthermore, these strains can colonize for longer than 72h and
induce severe inflammation in the intestine, which may induce fish death. We also
found that infected fish can transmit the pathogen into naive fish. Moreover, we
have established that zebrafish is an excellent model for vaccine study.
Successive triple bath vaccination with heat-killed single serotype S.
Typhimurium and S. Enteritidis immunogen induced protective efficacy against a
high dose (10(8)CFU/ml) of infection with these pathogens. This study provides a
natural infection model for the study of NTS infection, transmission and vaccine
efficacy.
PMID- 27614780
TI - Changes in prevalence of ovine paratuberculosis following vaccination with
Gudair(r): Results of a longitudinal study conducted over a decade.
AB - Since its registration in 2002, Gudair(r) vaccine has become the key tool for
managing paratuberculosis in sheep in Australia. This study was conducted to
evaluate its effectiveness in reducing paratuberculosis prevalence in 12 flocks
over more than one decade. Flocks with variable initial prevalence (5, 4 and 3
with low, medium, and high prevalence, respectively) were enrolled in the study
in 2003-04. Six biennial faecal samplings were conducted in these flocks over a
10year period. At each sampling, faeces from four age groups (3, 4, 5 and 6year
old sheep) were collected from each flock. The aim was to select 7 or 14 pools of
faeces constituted with pellets from 50 or 25 sheep from each age group,
respectively, but the numbers and sizes of pools did vary due to logistical
issues. Samples were cultured using pooled faecal culture approach and sheep
level paratuberculosis prevalence was estimated. Changes in probability of a pool
being positive and in paratuberculosis prevalence over time were evaluated by
fitting generalised-linear and linear mixed models. The proportion of positive
faecal pools significantly declined over time from 50.3% at the first sampling in
2003-04 to only 3.1% at the last sampling in 2013-14, suggestive of a 30-fold
reduction in the odds of a pooled faecal sample to be positive (p<0.001).
Similarly, the average animal level prevalence in flocks dropped from 7.64% at
the first sampling to 0.12% at the last sampling. However, faecal shedding
persisted and was still present in 3 of the 8 flocks (37.5%) that remained in the
study at the last sampling conducted in 2013-14. This is the longest study ever
conducted to evaluate paratuberculosis vaccine effectiveness. The results will
enable sheep producers to make informed decisions on managing paratuberculosis,
and in evaluating the risks of purchasing and trading vaccinated sheep.
PMID- 27614781
TI - Single-particle characterization of oncolytic vaccinia virus by flow virometry.
AB - Vaccinia virus (VV) is an oncolytic virus that is currently being evaluated as a
promising cancer vaccine in several phase I, II and III clinical trials. Although
several quality control tests are performed on each new batch of virus, these do
not routinely include a systematic characterization of virus particle
homogeneity, or relate the infectious titer to the total number of submicron
sized particles (SSPs) present in the sample. SSPs are comprised of infectious
virus and non-infectious viral particles, but also cell contaminants derived from
the virus isolation procedures, such as cellular vesicles and debris. Here we
have employed flow virometry (FV) analysis and sorting to isolate and
characterize distinct SSP populations in therapeutic oncolytic VV preparations.
We show that VV preparations contain SSPs heterogeneous in size and include large
numbers of non-infectious VV particles. Furthermore, we used FV to illustrate how
VV has a propensity to aggregate over time and under various handling and storage
procedures. Accordingly, we find that together the infectious titer, the total
number of SSPs, the number of viral genomes and the level of particle aggregation
in a sample constitute useful parameters that greatly facilitate inter-sample
assessment of physical quality, and also provides a means to monitor sample
deterioration over time. Additionally, we have successfully employed FV sorting
to further isolate virus from other particles by identifying a lipophilic dye
that preferentially stains VV over other SSPs in the sample. Overall, we
demonstrate that FV is a fast and effective tool that can be used to perform
quality, and consistency control assessments of oncolytic VV vaccine
preparations.
PMID- 27614782
TI - Vaccine purchasing groups in the United States: An overview of their policies and
practices.
AB - BACKGROUND: Vaccine purchasing groups (VPGs) may help reduce the upfront cost of
vaccines. The objective of this study was to describe key business practices of
VPGs in the United States. METHODS: Semi-structured, qualitative telephone
interviews were conducted with representatives from 11 VPGs, based on a sampling
frame of 53 VPGs. Interviews were transcribed and summarized by topic. RESULTS:
Characteristics of the 11 VPGs interviewed reflect the broader VPG population:
64% national vs 36% regional; 8% charge a membership fee; membership ranging from
40 to over 300,000 sites. VPGs establish agreements with vaccine manufacturers,
typically with either GlaxoSmithKline or Merck and Sanofi Pasteur; 1 VPG reported
a single-product (Trumenba) agreement with Pfizer. VPG agreements specify
"product loyalty" benchmarks (proportion of that manufacturer's product line)
that the VPG and its members must meet to receive discounted vaccine pricing. The
amount of discount is considered proprietary. Practices may actively participate
with only one VPG; the member discount is automatically applied by the
manufacturer at the time of ordering. Vaccine manufacturers monitor sales data to
ensure compliance with product loyalty terms; practices that do not meet
benchmarks may be removed from the VPG. VPGs are paid administration fees by the
manufacturers. VPGs use these fees to cover their operating expenses and often
rebate a portion of these fees back to their members. All 11 VPGs offer
additional services to members, ranging from immunization-focused education and
technical assistance to discounts on a broad range of medical and business
supplies. CONCLUSIONS: VPGs can facilitate access to reduced purchase prices for
most vaccines routinely recommended in the United States. Data on the magnitude
of the price reductions were not publicly available. VPG members must balance
loyalty-based price reductions against considerations of having a wider choice of
vaccine products.
PMID- 27614783
TI - Considerations for sustainable influenza vaccine production in developing
countries.
AB - Through its Global Action Plan for Influenza Vaccines (GAP), the World Health
Organization (WHO) in collaboration with the United States Department of Health
and Human Services has produced a checklist to support policy-makers and
influenza vaccine manufacturers in identifying key technological, political,
financial, and logistical issues affecting the sustainability of influenza
vaccine production. This checklist highlights actions in five key areas that are
beneficial for establishing successful local vaccine manufacturing. These five
areas comprise: (1) the policy environment and health-care systems; (2)
surveillance systems and influenza evidence; (3) product development and
manufacturing; (4) product approval and regulation; and (5) communication to
support influenza vaccination. Incorporating the checklist into national vaccine
production programmes has identified the policy gaps and next steps for countries
involved in GAP's Technology Transfer Initiative. Lessons learnt from country
experiences provide context and insight that complement the checklist's goal of
simplifying the complexities of influenza prevention, preparedness, and vaccine
manufacturing.
PMID- 27614785
TI - Expression of a phosphate-starvation inducible fructose-1,6-bisphosphatase gene
in common bean nodules correlates with phosphorus use efficiency.
AB - While increased P-hydrolysing acid phosphatases (APase) activity in bean nodules
is well documented under phosphorus (P) limitation, gene expression and
subcellular localization patterns within the N2-fixing nodule tissues are poorly
understood. The aim of this research was to track the enzyme activity along with
the intra-nodular localization of fructose-1,6-bisphosphatase (FBPase), and its
contribution to P use efficiency (PUE) under symbiotic nitrogen fixation (SNF) in
Phaseolus vulgaris. The FBPase transcript were localized in situ using RT-PCR and
the protein activity was measured in nodules of two contrasting recombinant
inbred lines (RILs) of P. vulgaris, namely RILs 115 (P-efficient) and 147 (P
inefficient), that were grown under sufficient versus deficient P supply. Under P
deficiency, higher FBPase transcript fluorescence was found in the inner cortex
as compared to the infected zone of RIL115. In addition, both the specific FBPase
and total APase enzyme activities significantly increased in both RILs, but to a
more significant extent in RIL115 as compared to RIL147. Furthermore, the
increased FBPase activity in nodules of RIL115 positively correlated with higher
use efficiency of both the rhizobial symbiosis (23%) and P for SNF (14%
calculated as the ratio of N2 fixed per nodule total P content). It is concluded
that the abundant tissue-specific localized FBPase transcript along with induced
enzymatic activity provides evidence of a specific tolerance mechanism where N2
fixing nodules overexpress under P-deficiency conditions. Such a mechanism would
maximise the intra-nodular inorganic P fraction necessary to compensate for large
amount of P needed during the SNF process.
PMID- 27614784
TI - Noncovalent Ubiquitin Interactions Regulate the Catalytic Activity of Ubiquitin
Writers.
AB - Covalent modification of substrate proteins with ubiquitin is the end result of
an intricate network of protein-protein interactions. The inherent ability of the
E1, E2, and E3 proteins of the ubiquitylation cascade (the ubiquitin writers) to
interact with ubiquitin facilitates this process. Importantly, contact between
ubiquitin and the E2/E3 writers is required for catalysis and the assembly of
chains of a given linkage. However, ubiquitin is also an activator of ubiquitin
writing enzymes, with many recent studies highlighting the ability of ubiquitin
to regulate activity and substrate modification. Here, we review the interactions
between ubiquitin-writing enzymes and regulatory ubiquitin molecules that promote
activity, and highlight the potential of these interactions to promote processive
ubiquitin transfer.
PMID- 27614786
TI - Immediate and potential long-term effects of consecutive heat waves on the
photosynthetic performance and water balance in Douglas-fir.
AB - The frequency and intensity of climatic extremes, such as heat waves, are
predicted to increase globally, with severe implications for terrestrial carbon
and water cycling. Temperatures may rise above critical thresholds that allow
trees to function optimally, with unknown long-term consequences for forest
ecosystems. In this context, we investigated how photosynthetic traits and the
water balance in Douglas-fir are affected by exposure to three heat waves with
temperatures about 12 degrees C above ambient. Photosynthetic carboxylation
efficiency (Vcmax) was mostly unaffected, but electron transport (Jmax) and
photosynthetic rates under saturating light (Asat) were strongly influenced by
the heat waves, with lagging limitations on photosynthesis still being observed
six weeks after the last heat wave. We also observed lingering heat-induced
inhibitions on transpiration, minimum stomatal conductance, and night-time
stomatal conductance (gs-night). Results from the stomatal models used to
calculate minimum stomatal conductance were similar to gs-night and indicated
changes in leaf morphology, e.g. stomatal occlusions and alterations in
epicuticular wax. Our results show Douglas-fir's ability to restrict water loss
following heat stress, but at the price of reduced photosynthetic performance.
Such limitations indicate potential long-term restrictions that heat waves can
impose on tree development and functioning under extreme climatic conditions.
PMID- 27614787
TI - Evaluation of a ketamine-based anesthesia package for use in emergency cesarean
delivery or emergency laparotomy when no anesthetist is available.
AB - OBJECTIVE: To assess the safety of a ketamine-based rescue anesthesia package to
support emergency cesarean delivery and emergency laparotomy when no anesthetist
was available. METHODS: A prospective case-series study was conducted at seven
sub-county hospitals in western Kenya between December 10, 2013, and January 20,
2016. Non-anesthetist clinicians underwent 5days of training in the Every Second
Matters-Ketamine (ESM-Ketamine) program. A database captured preoperative,
intraoperative, and postoperative details of all surgeries in which ESM-Ketamine
was used. The primary outcome measure was the ability of ESM-Ketamine to safely
support emergency operative procedures. RESULTS: Non-anesthetist providers
trained on ESM-Ketamine supported 83 emergency cesarean deliveries and 26
emergency laparotomies. Ketamine was administered by 10 nurse-midwives and six
clinical officers. Brief oxygen desaturations (<92% for <30s) were recorded among
5 (4.6%) of the 109 patients. Hallucinations occurred among 9 (8.3%) patients. No
serious adverse events related to the use of ESM-Ketamine were recorded.
CONCLUSION: The ESM-Ketamine package can be safely used by trained non
anesthetist providers to support emergency cesarean delivery and emergency
laparotomy when no anesthetist is available.
PMID- 27614788
TI - Evaluation of a simulation-based curriculum for implementing a new clinical
protocol.
AB - OBJECTIVE: To evaluate the implementation of a new clinical protocol utilizing on
unit simulation for team training. METHODS: A prospective observational study was
performed at the obstetrics unit of Von Voightlander Women's Hospital, Michigan,
USA, between October 1, 2012 to April 30, 2013. All members of the labor and
delivery team were eligible for participation. Traditional education methods and
in-situ multi-disciplinary simulations were used to educate labor and delivery
staff. Following each simulation, participants responded to a survey regarding
their experience. To evaluate the effect of the interventions, paging content was
analyzed for mandated elements and adherence to operating room entry-time
tracking was examined. RESULTS: In total, 51 unique individuals participated in
12 simulations during a 6-month period. Simulation was perceived as a valuable
activity and paging content improved. Following the intervention, the inclusion
of a goal time for reaching the operation room increased from 7% to 61% of pages
and the proportion of patients entering to operating room within 10 minutes of
the stated goal increased from 67% to 85%. CONCLUSION: The training program was
well received, and the accuracy of the communication and the goal set for
reaching the operating room improved.
PMID- 27614789
TI - Intralipid supplementation in women with recurrent spontaneous abortion and
elevated levels of natural killer cells.
AB - OBJECTIVE: To investigate the efficacy of intralipid supplementation in women
with recurrent spontaneous abortion (RSA) and elevated natural killer cell
activity undergoing in vitro fertilization/intracytoplasmic sperm injection.
METHODS: Between February 10, 2013, and April 30, 2015, a double-blind randomized
controlled study was conducted at a center in Egypt. Women with unexplained
secondary infertility, RSA, and elevated levels of natural killer cells (>12%)
were enrolled and randomly assigned to receive intralipid (2mL diluted at 20% in
250mL saline) or saline (250mL) infusion on the day of oocyte retrieval using
random numbers and sealed envelopes. Patients and attending physicians were
masked to group assignment. The infusions were repeated within 1week of a
positive pregnancy test and then every 2weeks until the end of the first
trimester. The primary outcome was chemical pregnancy 14days after embryo
transfer. Analyses were by intention-to-treat. RESULTS: Overall, 296 women were
enrolled. Chemical pregnancy was recorded for 84 (58.3%) of 144 women in the
intralipid group and 76 (50.0%) of 152 in the control group (P=0.129).
CONCLUSION: Intralipid supplementation did not increase frequency of chemical
pregnancy. However, findings related to ongoing pregnancy and live birth should
be investigated further. ClinicalTrials.gov:NCT01788540.
PMID- 27614790
TI - Is a single isocenter sufficient for volumetric modulated arc therapy
radiosurgery when multiple itracranial metastases are spatially dispersed?
AB - Previous work demonstrated improved dosimetry of single isocenter volumetric
modulated arc therapy (VMAT) of multiple intracranial targets when they are
located <= 4cm from isocenter because of narrower multileaf collimators (MLCs).
In follow-up, we sought to determine if decreasing isocenter-target distance
(diso) by using 2 to 3 isocenters would improve dosimetry for spatially dispersed
targets. We also investigated the effect of a maximum dose constraint during VMAT
optimization, and the dosimetric effect of the number of VMAT arcs used for a
larger number of targets (i.e., 7 to 9). We identified radiosurgery cases that
had multiple intracranial targets with diso of at least 1 target > 5cm. A single
isocenter VMAT plan was created using a standardized 4-arc technique with 18Gy
per target. Each case was then replanned (1) using 2 to 3 isocenters, (2)
including a maximum dose constraint per target, and in the case of 7 to 9
targets, (3) using 3 to 6 arcs. Dose evaluation included brain V6Gy and V12Gy,
and conformity index (CI), gradient index (GI), and heterogeneity index (HI) per
target. Two isocenters were sufficient to limit diso to <= 4cm and <= 5cm for
11/15 and 13/15 cases, respectively; after replanning with 2 to 3 isocenters,
diso decreased from 5.8 +/- 2.8cm (2.3 14.9) to 2.5 +/- 1.4cm (0 5.2). All dose
statistics improved on average, albeit modestly: V6Gy = 6.9 +/- 7.1%, V12Gy =
0.9% +/- 4.4%, CI = 2.6% +/- 4.6%, GI = 0.9% +/- 12.7%, and HI = 2.6% +/- 5.2%;
however, the number of arcs doubled and monitor units increase by nearly 2-fold.
A maximum dose constraint had a negative effect on all dose indices, increasing
V12Gy by 9.7 +/- 6.9%. For >= 7 targets, increasing number of arcs to > 3
improved CI, V12Gy, and V6Gy. A single isocenter is likely sufficient for VMAT
radiosurgery of multiple intracranial metastases. Optimal treatment plan quality
is achieved when no constraint is placed on the maximum target dose; for cases
with many targets at least 4 arcs are needed for optimal plan quality.
PMID- 27614791
TI - Relationship between pulmonary hyperinflation and dyspnoea severity during acute
exacerbations of cystic fibrosis.
AB - BACKGROUND AND OBJECTIVE: Acute exacerbations of cystic fibrosis (CF) occur
frequently throughout the course of the disease. Dyspnoea is the most common and
distressing symptom experienced by patients during these episodes. We tested the
hypothesis that pulmonary hyperinflation is an important determinant of dyspnoea
severity during acute exacerbations. METHODS: We studied patients during an acute
exacerbation of CF. Lung volumes, spirometry and dyspnoea scores were measured at
Day 0, Day 7, at the end of treatment (EOT) and 14 days following the EOT.
RESULTS: At the start of treatment, mean residual volume (RV)/total lung capacity
(TLC) was 54.9%, which decreased significantly with treatment, as did vital
capacity (VC), inspiratory capacity (IC) and dyspnoea scores. IC was the only
independent predictor of dyspnoea severity. CONCLUSION: Our study demonstrates
significant improvements in hyperinflation, spirometry and dyspnoea scores with
treatment of acute exacerbations of CF. Hyperinflation, rather than airflow
limitation, may contribute towards the increased dyspnoea during exacerbations.
PMID- 27614793
TI - Novel and powerful 3D adaptive crisp active contour method applied in the
segmentation of CT lung images.
AB - The World Health Organization estimates that 300 million people have asthma, 210
million people have Chronic Obstructive Pulmonary Disease (COPD), and, according
to WHO, COPD will become the third major cause of death worldwide in 2030.
Computational Vision systems are commonly used in pulmonology to address the task
of image segmentation, which is essential for accurate medical diagnoses.
Segmentation defines the regions of the lungs in CT images of the thorax that
must be further analyzed by the system or by a specialist physician. This work
proposes a novel and powerful technique named 3D Adaptive Crisp Active Contour
Method (3D ACACM) for the segmentation of CT lung images. The method starts with
a sphere within the lung to be segmented that is deformed by forces acting on it
towards the lung borders. This process is performed iteratively in order to
minimize an energy function associated with the 3D deformable model used. In the
experimental assessment, the 3D ACACM is compared against three approaches
commonly used in this field: the automatic 3D Region Growing, the level-set
algorithm based on coherent propagation and the semi-automatic segmentation by an
expert using the 3D OsiriX toolbox. When applied to 40 CT scans of the chest the
3D ACACM had an average F-measure of 99.22%, revealing its superiority and
competency to segment lungs in CT images.
PMID- 27614792
TI - Gland segmentation in colon histology images: The glas challenge contest.
AB - Colorectal adenocarcinoma originating in intestinal glandular structures is the
most common form of colon cancer. In clinical practice, the morphology of
intestinal glands, including architectural appearance and glandular formation, is
used by pathologists to inform prognosis and plan the treatment of individual
patients. However, achieving good inter-observer as well as intra-observer
reproducibility of cancer grading is still a major challenge in modern pathology.
An automated approach which quantifies the morphology of glands is a solution to
the problem. This paper provides an overview to the Gland Segmentation in Colon
Histology Images Challenge Contest (GlaS) held at MICCAI'2015. Details of the
challenge, including organization, dataset and evaluation criteria, are
presented, along with the method descriptions and evaluation results from the top
performing methods.
PMID- 27614794
TI - Clinical markers of neurodegeneration in Chinese patients with idiopathic rapid
eye movement sleep behavior disorder.
AB - OBJECTIVE: It is reported that neurodegenerative markers of Parkinson's disease
occur in patients with idiopathic rapid eye movement sleep behavior disorder
(idiopathic RBD); however, it has been unknown in Chinese patients. This study
aims to provide a detailed understanding of the clinical features of Chinese
patients with idiopathic RBD. METHODS: We conducted a series of Parkinson related
motor and non-motor assessments in 181 participants including 41 patients with
idiopathic RBD, 35 Parkinson's patients without RBD, 42 Parkinson's patients with
RBD, and 63 healthy controls. The RBD questionnaire -Hong Kong (RBDQ-HK) was used
to confirm clinical RBD symptoms and evaluate the severity. Motor function
including Unified Parkinson's disease Rating Scale (UPDRS), alternative tap test,
Purdue Pegboard test and Timed Up and Go test, and non-motor functions including
olfaction, cognition, and autonomic function were assessed in each group.
RESULTS: Motor assessments of UPDRS, Purdue Pegboard, and Timed Up and Go, and
the systolic blood pressure (BP) drop in patients with idiopathic RBD were
intermediate between controls and Parkinson's patients. However, the alternative
tap test and some non- motor functions including olfaction and orthostatic
symptoms in idiopathic RBD were impaired as seriously as in Parkinson's disease.
No difference was found in urinary and bowel function between idiopathic RBD and
controls. In idiopathic RBD, functional impairment was associated with age and
the severity of RBD symptoms (p<0.05). In addition, systolic BP drops closely
correlated to motor function and bowel function (p<0.05). CONCLUSIONS: Chinese
patients with idiopathic RBD demonstrated an extensive and heterogeneous
functional impairment. The association between functional impairment and age and
the severity of RBD symptoms needs to be determined in future studies.
PMID- 27614795
TI - Hydrolytic enzyme activities in shiitake mushroom (Lentinula edodes) strains
cultivated on coffee pulp.
AB - Hydrolytic enzyme production (cellulases, laminarinases and xylanases) was
studied in cultures of Lentinula edodes on sterilized coffee pulp. Samples of
substrate colonized by mycelia were taken after 7, 14, 21, 28 and 35 days of
incubation at 25 degrees C (W1 to W5) and during the fruiting period at different
stages: formation of primordia (PF), first harvest (H) and one week after the
first harvest (PH). The enzymatic activity was lower during the early mycelial
growth and showed higher levels during the formation and development of fruiting
bodies. During the reproductive stage of the fungus, the samples were subjected
to a soaking treatment; however, it was not possible to relate this soaking
treatment to the increase in enzyme production. The levels of enzymatic activity
suggest that secretion of the studied enzymes does not influence the adaptability
of the strains to the substrate.
PMID- 27614797
TI - Harnessing Nanoparticles for Immune Modulation: (Trends in Immunology 36, 419
427; July 2016).
PMID- 27614796
TI - [Fungal biomass estimation in soils from southwestern Buenos Aires province
(Argentina) using calcofluor white stain].
AB - Soil microorganisms are vital for ecosystem functioning because of the role they
play in soil nutrient cycling. Agricultural practices and the intensification of
land use have a negative effect on microbial activities and fungal biomass has
been widely used as an indicator of soil health. The aim of this study was to
analyze fungal biomass in soils from southwestern Buenos Aires province using
direct fluorescent staining and to contribute to its use as an indicator of
environmental changes in the ecosystem as well as to define its sensitivity to
weather conditions. Soil samples were collected during two consecutive years.
Soil smears were prepared and stained with two different concentrations of
calcofluor, and the fungal biomass was estimated under an epifluorescence
microscope. Soil fungal biomass varied between 2.23 and 26.89MUg fungal C/g soil,
being these values in the range expected for the studied soil type. The fungal
biomass was positively related to temperature and precipitations. The methodology
used was reliable, standardized and sensitive to weather conditions. The results
of this study contribute information to evaluate fungal biomass in different soil
types and support its use as an indicator of soil health for analyzing the impact
of different agricultural practices.
PMID- 27614800
TI - Bone marrow transplantation for MHC class I deficiency corrects T-cell immunity
but dissociates natural killer cell repertoire formation from function.
PMID- 27614799
TI - mTOR-Mediated Regulation of Dendritic Cell Differentiation and Function.
AB - Dendritic cells (DCs) are essential antigen-presenting cells that sample the
extra- and intracellular milieu to process antigens for the instruction of T cell
responses. The mammalian target of rapamycin (mTOR) network senses environmental
cues and is important for numerous cellular processes. This review discusses how
DCs use mTOR complexes (mTORC1 and 2) to adapt their cellular metabolism,
transcriptional responses, and translation machinery to control DC development,
antigen processing, cytokine production, and T cell stimulation. We present a
spatiotemporal model suggesting that the mTOR network integrates pattern
recognition and growth factor receptor activation with nutritional information
from the cell and surrounding tissue to support T cell stimulation and tolerance.
mTOR develops into a central player that regulates DC differentiation and immune
functions.
PMID- 27614801
TI - Effect of omega-3 fatty acid supplementation on arterial elasticity in patients
with familial hypercholesterolaemia on statin therapy.
AB - BACKGROUND AND AIMS: Increased arterial stiffness is closely linked with raised
blood pressure that contributes substantially to enhanced risk of coronary heart
disease in high risk individuals with familial hypercholesterolaemia (FH). Omega
3 fatty acid (omega3-FA) supplementation has been demonstrated to lower blood
pressure in subjects with a high cardiovascular disease risk. Whether omega3-FA
supplementation improves arterial stiffness in FH subjects, on background statin
therapy, has yet to be investigated. METHOD AND RESULTS: We carried out an 8-week
randomized, crossover intervention trial to test the effect of 4 g/d omega3-FA
supplementation (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on
arterial elasticity in 20 adults with FH on optimal cholesterol-lowering therapy.
Large and small artery elasticity were measured by pulse contour analysis of the
radial artery. omega3-FA supplementation significantly (P < 0.05 in all)
increased large artery elasticity (+9%) and reduced systolic blood pressure (-6%)
and diastolic blood pressure (-6%), plasma triglycerides (-20%), apoB
concentration (-8%). In contrast, omega3-FAs had no significant effect on small
artery elasticity. The change in large artery elasticity was not significantly
associated with changes in systolic blood pressure or plasma triglyceride
concentration. CONCLUSIONS: omega3-FA supplementation improves large arterial
elasticity and arterial blood pressure independent of statin therapy in adults
with FH. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.com/NCT01577056.
PMID- 27614802
TI - Sunbeds' ultraviolet radiation measurements with different radiometers and
criteria for compliance assessment set by the national competent authority in
Greece.
AB - In order to ground the credibility of the sunbeds' ultraviolet radiation
compliance assessment with the 0.3W/m(2) erythema effective irradiance limit, it
is highly important to use reliable measuring equipment and to justify reasonably
the measurement's result. Recently, the first surveillance action of the
artificial tanning sector in Greece has been finalised. The action consisted of
in situ erythema effective irradiance measurements from sunbeds at commercial
premises offering artificial tanning services at various cities throughout
Greece. Four different broadband erythemal weighted radiometers were used in
order to compare them during in situ sunbeds' radiation measurements, at
commercial premises, and to choose the most suitable one for compliance
inspections. Furthermore a rationale has been introduced in order to compare the
measurement's result with the limit, and decide about compliance or not, taking
into account the measurement's expanded uncertainty. According to this approach,
compliance, probable compliance or non-compliance is verified when the
measurement's result taking into account the measurement's expanded uncertainty
does not, probably or does exceed the 0.3W/m(2) limit, respectively. Ultraviolet
radiation exceeded the 0.3W/m(2) erythema effective irradiance limit in 63.5% (33
out of 52) of the sunbeds and probably exceeded the limit in 11.5% (6 out of 52)
of the sunbeds, according to the measurements performed with the radiometer which
was chosen as the most suitable one and the proposed rationale for compliance
justification.
PMID- 27614798
TI - Present Yourself! By MHC Class I and MHC Class II Molecules.
AB - Since the discovery of MHC molecules, it has taken 40 years to arrive at a
coherent picture of how MHC class I and MHC class II molecules really work. This
is a story of the proteases and MHC-like chaperones that support the MHC class I
and II molecules in presenting peptides to the immune system. We now understand
that the MHC system shapes both the repertoire of presented peptides and the
subsequent T cell response, with important implications ranging from transplant
rejection to tumor immunotherapies. Here we present an illustrated review of the
ins and outs of MHC class I and MHC class II antigen presentation.
PMID- 27614803
TI - Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid
Abnormalities in High-Fructose-Fed Mice.
AB - OBJECTIVES: High intake of dietary fructose causes perturbation in lipid
metabolism and provokes lipid-induced insulin resistance. A rise in
glucocorticoids (GCs) has recently been suggested to be involved in fructose
induced insulin resistance. The objective of the study was to investigate the
effect of GC blockade on lipid abnormalities in insulin-resistant mice. METHODS:
Insulin resistance was induced in mice by administering a high-fructose diet
(HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to
HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC
levels, the glucocorticoid receptor (GR) activation and the expression of GC
regulated genes involved in lipid metabolism were examined. RESULTS: HFrD
elevated the intracellular GC content in both liver and adipose tissue and
enhanced the GR nuclear translocation. The plasma GC level remained unchanged.
The levels of free fatty acids and triglycerides in plasma were elevated,
accompanied by increased plasma insulin and glucose levels and decreased hepatic
glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC
levels and the expression of GC-targeted genes involved in lipid accumulation,
and it improved insulin sensitivity. CONCLUSIONS: This study demonstrated that
HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced
GC in liver and adipose tissue and that GC antagonism might reduce fructose
induced lipid abnormalities and insulin resistance.
PMID- 27614804
TI - Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer
Disease: A Systematic Review.
AB - Basic and clinical research support a link between diabetes mellitus and
Alzheimer disease (AD). However, the relationship with AD progression is unclear.
This review focuses on the association between diabetes and cognitive decline in
patients with AD. The literature published through May 2015 was searched in 3
databases: PubMed, Embase and Cochrane. Studies evaluating the effects of
diabetes on patients with AD or cognitive decline were included, and extracted
data were analyzed. A total of 10 articles met the inclusion criteria for review.
The results of these studies were inconsistent in terms of the association
between diabetes and cognitive decline. Only 2 studies demonstrated that the
presence of diabetes was independently related to the progression of cognitive
decline in the patients with AD, and 3 studies suggested that histories of
diabetes were not correlated with the changes in cognitive function in patients
with AD. Half of the included studies even indicated that histories of diabetes
were associated with lesser declines in cognitive function in patients with AD.
Current evidence indicates that the link between diabetes and cognitive decline
in patients with AD is uncertain. Further clinical studies are needed, with
larger samples, long-term follow up and an extended battery of cognitive
assessments.
PMID- 27614805
TI - Predictors of Comorbid Eating Disorders and Diabetes in People with Type 1 and
Type 2 Diabetes.
AB - OBJECTIVES: The objective of this study was to identify psychosocial predictors
of comorbid eating disorders (EDs) in individuals with type 1 and type 2
diabetes. METHODS: In this cross-sectional study, 140 people with diabetes
answered an online survey covering sociodemographic information, body esteem,
restrictive eating, medication omission, coping styles and depressive symptoms.
Participants were recruited through advertisements on more than 100 websites,
including forums, community organizations and Facebook groups focusing on either
diabetes or EDs. Recruitment took place in Canada, Europe, Australia and the
United States. RESULTS: On average, EDs developed after diabetes diagnoses in
participants with type 1 diabetes but prior to diabetes diagnosis in participants
with type 2 diabetes. In type 1 diabetes, avoidance coping styles and depressive
symptoms predicted an additional diagnosis of EDs. Co-occurring EDs and type 2
diabetes were predicted by body mass indexes and task-oriented coping strategies.
CONCLUSIONS: Variables potentially influencing the development of EDs in people
with diabetes differ according to the type of diabetes, body mass indexes, coping
styles and depressive symptoms; they should be more systematically evaluated and
closely monitored. In the context of diabetes management, prevention strategies
for ED onset based on increased knowledge of the risk factors associated with EDs
are necessary and could help decrease the risk for the health complications of
diabetes.
PMID- 27614806
TI - Insulin Signalling: The Inside Story.
AB - Insulin signalling begins with binding to its cell surface insulin receptor (IR),
which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently
autophosphorylated and activated to tyrosine phosphorylate key cellular
substrates that are essential for entraining the insulin response. Although IRK
activation begins at the cell surface, it is maintained and augmented following
internalization into the endosomal system (ENS). The peroxovanadium compounds
(pVs) were discovered to activate the IRK in the absence of insulin and lead to a
full insulin response. Thus, IRK activation is both necessary and sufficient for
insulin signalling. Furthermore, this could be shown to occur with activation of
only the endosomal IRK. The mechanism of pV action was shown to be the inhibition
of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that
the duration and intensity of insulin signalling are modulated within ENS by the
recruitment of cellular substrates to ENS; intra-endosomal acidification, which
promotes dissociation of insulin from the IRK; an endosomal acidic insulinase,
which degrades intra-endosomal insulin; and IRK-associated PTPs, which
dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of
IRKs is central to insulin signalling and its regulation.
PMID- 27614807
TI - Mucous fistula refeeding decreases parenteral nutrition exposure in postsurgical
premature neonates.
AB - BACKGROUND/PURPOSE: Premature neonates can develop intraabdominal conditions
requiring emergent bowel resection and enterostomy. Parenteral nutrition (PN) is
often required, but results in cholestasis. Mucous fistula refeeding allows for
functional restoration of continuity. We sought to determine the effect of
refeeding on nutrition intake, PN dependence, and PN associated hepatotoxicity
while evaluating the safety of this practice. METHODS: A retrospective review of
neonates who underwent bowel resection and small bowel enterostomy with or
without mucous fistula over 2years was undertaken. Patients who underwent mucous
fistula refeeding (RF) were compared to those who did not (OST). Primary outcomes
included days from surgery to discontinuation of PN and goal enteral feeds, and
total days on PN. Secondary outcomes were related to PN hepatotoxicity. RESULTS:
Thirteen RF and eleven OST were identified. There were no significant differences
among markers of critical illness (p>0.20). In the interoperative period, RF
patients reached goal enteral feeds earlier than OST patients (median 28 versus
43days; p=0.03) and were able to have PN discontinued earlier (median 25 versus
41days; p=0.04). Following anastomosis, the magnitude of effect was more
pronounced, with RF patients reaching goal enteral feeds earlier than OST
patients (median 7.5 versus 20days; p<=0.001) and having PN discontinued sooner
(30.5 versus 48days; p=0.001). CONCLUSIONS: RF neonates reached goal feeds and
were able to be weaned from PN sooner than OST patients. A prospective
multicenter trial of refeeding is needed to define the benefits and potential
side effects of refeeding in a larger patient population in varied care
environments.
PMID- 27614809
TI - Management of nontuberculous mycobacterial lymphadenitis in a tertiary care
children's hospital: A 20year experience.
AB - PURPOSE: Nontuberculous mycobacteria are uncommon cause of chronic cervicofacial
lymphadenitis in healthy children. We describe clinical features and management
strategies of cervicofacial nontuberculous mycobacterium lymphadenitis in a
tertiary pediatric hospital. METHODS: Retrospective analysis of medical records
of children discharged from 1992 to 2014 with a diagnosis of cervicofacial
nontuberculous mycobacterium was made. Diagnosis certainty was based on
microhistological investigations. Clinical stage was evaluated according to lymph
node size and presence of fistulas. Successful therapy was defined by the
regression of the lymph node enlargement (>75%) or complete surgical excision
without relapse. RESULTS: Cervicofacial nontuberculous mycobacterium was
diagnosed in 33 patients. Complete excision was performed in 73% of cases
primarily observed in our hospital, while 83% of those referred from other
hospitals required further surgical treatment. No case of relapse was observed
after one year of follow-up. CONCLUSIONS: We recommend surgical approach as the
first therapeutic option in the management of cervicofacial nontuberculous
mycobacterium lymphadenitis. LEVELS OF EVIDENCE: Prognosis and Retrospective
Study - Level II.
PMID- 27614808
TI - The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia
in cryptorchid boys and the subsequent risk of testicular cancer in men with
prepubertal surgery for syndromic or non-syndromic cryptorchidism.
AB - INTRODUCTION: Cryptorchidism is a risk factor for testicular cancer in adult
life. It remains unclear how prepubertal surgery for cryptorchidism impacts later
development of adult testicular cancer. The aim of study was to investigate tools
to identify the cryptorchid boys who later develop testicular cancer. METHODS:
The study cohort consisted of 1403 men operated prepubertally/pubertally for
undescended testis between 1971 and 2003. At surgery testicular biopsies were
taken from the cryptorchid testes. The boys were followed for occurrence of
testicular cancer. The testicular cancer risk was compared to the risk in the
Danish Population. Testicular biopsies from the boys who developed testicular
cancer during follow-up underwent histological examination with specific
diagnostic immunohistochemical markers for germ cell neoplasia. RESULTS: The
cohort was followed for 33,627 person years at risk. We identified 16 cases with
testicular cancer in adulthood. The standardized incidence ratio was 2.66 (95%
CI: 1.52-4.32). At time of primary surgery in prepubertal/pubertal age
Intratubular Germ Cell Neoplasia (ITGCN) was diagnosed in 5 cases and the boys
were unilaterally orchiectomized. At follow-up new immunohistochemical staining
indicated ITGCN in two of the 16 cancer cases at reevaluation of the original
biopsies from time of prepubertal/pubertal surgery. One had syndromic cryptorchid
and developed seminoma, and another showed nonsyndromic cryptorchidism and
developed embryonic teratocarcinoma. Totally, ITGCN was diagnosed in 0.5%
(7/1403) of prepubertal cryptorchid boys, whereof 57% (4/7) in syndromic
cryptorchidism. DISCUSSION: ITGCN is predominantly observed prepubertally in boys
with syndromic-cryptorchidism. In nonsyndromic cryptorchidism testicular cancer
develops postpubertally, generally not based on dormant germ cells of ITGCN
caused by an early fetal maldevelopment. LEVELS OF EVIDENCE: LEVEL I.
PMID- 27614810
TI - Comparison of transumbilical multiport and standard laparoscopic pyeloplasty in
children: Mid-term results at a single center.
AB - OBJECTIVE: To compare the efficacy of transumbilical multiport (TMLP) and
standard laparoscopic pyeloplasty (SLP) for the treatment of congenital
ureteropelvic junction obstruction in children. METHODS: Forty-eight patients
were included in this matched-pair study. The TMLP applied three transumbilical
incisions for one 5-mm and two 3-mm ports, whereas SLP was undertaken with
traditional three-port technique. The demographic, perioperative, and follow-up
data were retrospectively compared between TMLP (n=24) and SLP (n=24) groups.
RESULTS: Two groups were matched according to patient's age, gender, laterality,
weight, and surgical indication. TMLP and SLP were successfully performed in all
patients, without conversion to open procedure. There was no significant
difference between both groups in intraoperative blood loss, time to oral
feeding, time to normal activities, pain scores, or complication rates. Longer
mean operative time (125.4+/-21.6 vs. 112.2+/-25.2 min; P=0.012) and better
patient satisfaction (30.4+/-4.5 vs. 24.6+/-3.4; P=0.026) were noted in TMLP
group than those in SLP group. Mid-term follow-up indicated no significant
difference in postoperative alleviation of hydronephrosis or improvement of renal
function. CONCLUSION: TMLP is a feasible and efficient procedure for the
management of congenital ureteropelvic junction obstruction in children, with
comparative outcome and better cosmetic results than SLP.
PMID- 27614811
TI - Comparative Study of Survival following Videothoracoscopic Lobectomy Procedures
for Lung Cancer: Single- versus Multiple-port Approaches.
AB - INTRODUCTION: Video-assisted thoracoscopic surgery has become the technique of
choice in the early stages of lung cancer in many centers although there is no
evidence that all of the surgical approaches achieve the same long-term survival.
METHOD: We carried out a retrospective review of 276 VATS lobectomies performed
in our department, analyzing age, sex, comorbidities, current smoker, FEV1 and
FCV, surgical approach, TNM and pathological stage, histologic type, neoadjuvant
or coadjuvant chemotherapy, relapse and metastasis time, with the main aim of
evaluating the survival rate and disease-free time, especially with regard to the
two/three versus single port approach. RESULT: The one/four year global survival
rate was 88.1 and 67.6% respectively. Bivariate analysis found that the variables
associated with survival are comorbidity, histological type, stage, surgical
approach and need for chemotherapy. When we independently analyzed the surgical
approach, we found a lower survival rate in the single-port group vs. the
two/three-port group (VATS). Stratifying by tumoral stage (stage I) and by tumor
size (T2) survival was significantly lower for patients with single-port group in
comparison to VATS approach. In the multivariate analysis, single-port group is
associated with a higher risk of death (HR=1.78). In analyzing disease-free
survival, differences were found in both cases in favor of two/three port VATS:
p=.093 for local relapses and p=.091 for the development of metastasis.
CONCLUSIONS: These results challenge the use of the single port technique in
malignant lung pathologies, suggesting the need for clinical trials in order to
identify the role this technique may have in lung cancer surgery.
PMID- 27614812
TI - Hypoxia-induced epithelial-mesenchymal transition is regulated by phosphorylation
of GSK3-beta via PI3 K/Akt signaling in oral squamous cell carcinoma.
AB - OBJECTIVE: Epithelial-mesenchymal transition (EMT) plays an important role in
cancer invasion and metastasis induced by hypoxia. Here, we examined whether
phosphorylation of GSK3-beta via phosphoinositide 3-kinase (PI3 K)/Akt signaling
is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma
(OSCC). STUDY DESIGN: Experiments were performed in OSCC cell lines (HSC-2, HSC
3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was
assessed by Matrigel invasion assays and wound healing assays. OSCC cell lines
(HSC-2 and HSC-4) overexpressing hypoxia-inducible factor (HIF)-1alpha were
established to examine the effects of HIF-1alpha on EMT-related factors.
Immunohistochemical staining was performed to examine phosphorylation of GSK3
beta in 33 cases of tongue squamous cell carcinoma. RESULTS: Under hypoxic
conditions, OSCC cell lines exhibited HIF-1alpha expression and showed evidence
of the EMT. In cells overexpressing HIF-1alpha, the levels of phospho-Akt and
phospho-GSK3-beta were increased, resulting in induction of the EMT. Inhibition
of GSK3-beta phosphorylation suppressed these effects. Moreover, the intensity of
pGSK3-beta staining was significantly increased with cN stage and cTNM stage in
patients with tongue squamous cell carcinoma. CONCLUSIONS: Our data showed that
the hypoxia-induced EMT in OSCC was enhanced by GSK3-beta phosphorylation,
suggesting that GSK3-beta may be important in the invasion and metastasis of
OSCC.
PMID- 27614813
TI - Surgical correction without bone grafts of maxillofacial asymmetric deformities
in patients treated for unilateral temporomandibular joint ankylosis.
AB - OBJECTIVE: With the inclusion criteria of patients confirmed and the therapeutic
effects and stability evaluated, this article presents the clinical value of
bimaxillary orthognathic surgery without bone graft of maxillofacial asymmetric
deformities in patients treated for unilateral temporomandibular joint (TMJ)
ankylosis. STUDY DESIGN: From 2008 to 2012, 12 patients with dentomaxillofacial
asymmetric deformities secondary to unilateral TMJ ankylosis who had undergone
TMJ reconstruction as the primary surgery were included in the study.
Preoperatively, all patients had compensatory occlusal plane and maxillary
inclination <10 degrees and mandibular advancement <15 mm according to computer
assisted 3-dimensional surgical simulation and prediction. Patients received
LeFort I osteotomy and bilateral sagittal split rami osteotomy without bone
graft, and genioplasty. Pre- and postoperative and long-term radiographic
examinations were done to evaluate the therapeutic effects. RESULTS:
Maxillofacial asymmetry and abnormal occlusions in patients were clearly improved
in the parameters of facial appearance and occlusion as recorded pre- and
postoperatively and long term. All patients obtained satisfactory results and
were stable in the 36- to 50-month follow-up period. CONCLUSION: The bimaxillary
orthognathic treatment protocol without bone grafts described in this study can
provide stable improvement in facial appearance and occlusion of secondary
dentomaxillofacial deformities in appropriate patients with unilateral TMJ
ankylosis.
PMID- 27614815
TI - An Intervention to Promote Sleep and Reduce ADHD Symptoms.
AB - OBJECTIVE: To determine the effect of a sleep hygiene education module and
prescriptive sleep routine for children ages 5 through 11 years with attention
deficit hyperactivity disorder (ADHD). METHODS: The 20-week pilot project used a
pre-/posttest design to assess sleep and ADHD symptoms. The Child Sleep Habits
Questionnaire (CHSQ) and Vanderbilt Assessment Scale-Parent Form survey were
provided to assess sleep and ADHD behaviors of participants at baseline and 6
weeks after implementation of the sleep hygiene routine. Fifty-three children
participated in the project. Of these, 23 scored 42 or greater on the CHSQ,
indicating a sleep disorder, and received the intervention. RESULTS: The CHSQ and
Vanderbilt scores indicated a significant improvement in sleep quality and
reduction in ADHD symptoms after implementation of the sleep hygiene routine
(CHSQ: p < .001, d = .928; Vanderbilt Questions 1-9: p < .001, d = .473;
Vanderbilt Questions 10-18: p = .004; d = .329). CONCLUSION: A provider
instructed sleep hygiene routine in children with ADHD improves sleep quality and
reduces ADHD symptoms.
PMID- 27614814
TI - Postpartum Depression Screening at Well-Child Appointments: A Quality Improvement
Project.
AB - INTRODUCTION: The purpose of this quality improvement project was to implement
and evaluate a postpartum depression screening program using the Edinburgh
Postnatal Depression Scale (EPDS) during well-child appointments up to 1 year of
age at a private, faith-based primary care clinic. METHOD: The Plan-Do-Study-Act
framework was used in this quality improvement project. The EPDS was administered
to mothers ages 19 years and older at their infants' well-child appointments at a
faith-based clinic in the Midwest. A score of 10 or higher was considered a
positive result. The results were reviewed, and protocol changes were implemented
every 2 weeks using the Plan-Do-Study-Act framework. RESULTS: A total of 35
mothers completed the EPDS during the 9-week implementation period. Of 37 mothers
asked to participate, nearly all agreed (97.3%); there was one refusal (2.7%).
Staff compliance rate with administering the EPDS was 78.7%; there were 10 missed
opportunities (21.3%). There were five positive EPDS results (14.3%). Mothers who
screened positive were between the ages of 20 and 44 years. Infant ages were
between 2 weeks and 12 months. DISCUSSION: Screening mothers at well-child
appointments can identify women with postpartum depression. Not doing so is a
missed opportunity. The results of this project support the identification of
postpartum depression by screening using the EPDS during well-child appointments
up to 1 year of age.
PMID- 27614816
TI - Chemical Thromboprophylaxis Is Not Necessary to Reduce Risk of Thromboembolism
With Tranexamic Acid After Total Hip Arthroplasty.
AB - BACKGROUND: The major concern with the use of tranexamic acid is that it may
promote a hypercoagulable state and increase the risk of deep vein thrombosis
(DVT) and pulmonary embolism (PE), particularly when chemical thromboprophylaxis
is not used. The objective of this study was to ascertain whether tranexamic acid
reduces blood loss and transfusion amounts and increases the prevalence of DVT
and PE in the patients undergoing primary cementless total hip arthroplasty (THA)
without the use of routine chemical thromboprophylaxis. METHODS: There were 480
patients (582 hips) in the control group who did not receive tranexamic acid and
487 patients (584 hips) in the study group who received tranexamic acid.
Mechanical compression device was applied without any chemical
thromboprophylaxis. Transfusion rates and volumes were recorded. DVT was
diagnosed using both sonogram and venogram at 7 or 8 days postoperatively. All
patients had pre- and postoperative perfusion lung scanning to defect pulmonary
embolism (PE). RESULTS: Intraoperative (614 vs 389 mL) and postoperative blood
loss (515 vs 329 mL) and transfusion volumes (3 units vs 1.5 units) were
significantly lower (P < .001) in the tranexamic acid group. The prevalence of
DVT was 15% (87 of 582 hips) in the control group and 18% (105 of 584 hips) in
the tranexamic acid group. No fatal PE occurred in either group. CONCLUSION: The
use of tranexamic acid reduces the volume of blood transfusion and does not
increase the prevalence of DVT or PE in the patients who did not receive routine
chemical thromboprophylaxis after primary cementless THA.
PMID- 27614817
TI - Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce
intrahepatic antigen-specific immune responses.
AB - Targeting antigen combined with adjuvants to hepatic antigen-presenting cells
(APCs) is essential for the induction of intrahepatic T cellular immunity
controlling and resolving viral infections of the liver. Intravenous injection of
antigen-loaded nanoparticles is a promising approach for the delivery of antigens
to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively
of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant
monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed.
Aim of the present study was the evaluation of the in vitro and in vivo behavior
of MPLA-functionalized NS5A-NCs regarding the interaction with liver dendritic
cells (DCs) and the potential to induce intrahepatic immune responses in a mouse
model. Maturation of DCs was significantly increased by application of NS5A+MPLA
NCs compared to non-functionalized NS5A-NCs promoting a vigorous expression of
CD40, CD80, CD86 and a strong secretion of the Th1-related cytokine IL-12. NS5A
NCs were preferentially deposited in DCs and Kupffer cells residing in the liver
after intravenous administration. Immunization with NS5A-NCs induced intrahepatic
antigen-specific CD4(+) T cellular immune responses determined by the secretion
of IFNgamma and IL-2. Furthermore, supplementation with MPLA induced significant
levels of NS5A-specific antibodies. The application of polymeric nanocapsules
synthesized exclusively out of antigen avoids the risk of unintended side effects
caused by additional carrier substances. Functionalization with adjuvants like
MPLA and the efficient targeting to liver-resident APCs inherits the potential
for application of antigen nanocapsules in further vaccination approaches against
pathogens affecting the liver.
PMID- 27614818
TI - Multifunctional gold-based nanocomposites for theranostics.
AB - Although Au-particle potential in nanobiotechnology has been recognized for the
last 15 years, new insights into the unique properties of multifunctional
nanostructures have just recently started to emerge. Multifunctional gold-based
nanocomposites combine multiple modalities to improve the efficacy of the
therapeutic and diagnostic treatment of cancer and other socially significant
diseases. This review is focused on multifunctional gold-based theranostic
nanocomposites, which can be fabricated by three main routes. The first route is
to create composite (or hybrid) nanoparticles, whose components enable diagnostic
and therapeutic functions. The second route is based on smart bioconjugation
techniques to functionalize gold nanoparticles with a set of different molecules,
enabling them to perform targeting, diagnostic, and therapeutic functions in a
single treatment procedure. Finally, the third route for multifunctionalized
composite nanoparticles is a combination of the first two and involves additional
functionalization of hybrid nanoparticles with several molecules possessing
different theranostic modalities. This last class of multifunctionalized
composites also includes fluorescent atomic clusters with multiple
functionalities.
PMID- 27614819
TI - Influence of Intrinsic Factors on Erosive Tooth Wear in a Large-Scale
Epidemiological Study.
AB - OBJECTIVE: To assess the influence of self-reported intrinsic factors
[gastroesophageal reflux disease (GERD), long-term alcoholism, long-term heavy
use of alcohol and multiple pregnancies] on erosive tooth wear in a middle-aged
cohort sample. MATERIALS AND METHODS: Of the total Northern Finland Birth Cohort
(NFBC 1966), a convenience sample (n = 3,181) was invited for an oral health
examination in 2012-2013, of which 1,962 participated, comprising the final study
group. Erosive tooth wear was assessed by sextants using the Basic Erosive Wear
Examination Index (BEWE, 0-18). Clinical data were supplemented by questionnaires
conducted in 1997/1998 and 2012/2013. The participants were divided into severe
(BEWE sum >=9) and no-to-moderate (BEWE sum 0-8) erosive wear groups, and the
logistic regression model was applied. RESULTS: Selected intrinsic factors were
quite rare in this cohort sample and explained only 5.9% of the difference in the
prevalence and severity of erosive wear. Daily symptoms of GERD [odds ratio (OR)
3.8, confidence interval (CI) 1.2-12.0] and hyposalivation (OR 3.8, CI 1.2-11.8)
were the strongest risk indicators for severe erosive wear. Additionally,
variables associated with an elevated risk for severe erosive wear were diagnosed
alcoholism at any point (OR 2.5, CI 0.7-9.7) and self-reported heavy use of
alcohol in both questionnaires (OR 2.0, CI 0.6-6.2). Even low-dose long-term
consumption of alcohol was associated with erosive wear. CONCLUSIONS: In this
cohort sample, intrinsic factors such as GERD or alcoholism alone are relatively
uncommon causes of erosive tooth wear. The role of long-term use of alcohol in
the erosion process may be bigger than presumed.
PMID- 27614820
TI - Microbial responses to various process disturbances in a continuous hydrogen
reactor fed with galactose.
AB - In this study, microbial responses of a continuous hydrogen reactor fed with
galactose have been investigated. Process disturbances reduced H2 production
performance as well as large fluctuations in microbial diversity. The peak values
of the hydrogen yield (HY) was not influenced greatly during the steady state
period, and accounted as 2.01 +/- 0.05 and 2.14 +/- 0.03 mol/mol galactoseadded,
while hydraulic retention time (HRT) was at 12 and 8 h, respectively. Microbial
community analysis via 454 pyrosequencing revealed that functional redundancy
following changes in the microbial community distribution led to the stability of
the fermentation performance. The butyrate to acetate (B/A) ratio well correlated
with changes in the microbial community. The energy generation rate and energy
yield resulted in the peak values of 134 kJ/L-d and 612 kJ/moladded.
PMID- 27614821
TI - Callistiviminenes A-O: Diverse adducts of beta-triketone and sesqui- or
monoterpene from the fruits of Callistemon viminalis.
AB - Callistiviminenes A-O, fifteen adducts of beta-triketone with sesqui- or
monoterpene, along with a known compound, were isolated from the fruits of
Callistemon viminalis. Callistiviminenes A and B are beta-triketone-coupled (-)
bicyclosequiphellandrene contained an oxaspiro[5.5]undecene unit, and
callistiviminenes C-E are rare adducts of beta-triketone and bicyclogermacrene.
Their structures and absolute configurations were elucidated by spectroscopic and
computational methods, as well as by single-crystal X-ray diffraction experiment.
A plausible biosynthetic pathway to these compounds involves a hetero-Diels-Alder
reaction. Callistiviminenes C and D exhibited inhibition against
lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with
IC50 value of 20.3 MUM and 32.5 MUM, respectively.
PMID- 27614822
TI - Increased Failure Rate of Modified Double Arthrodesis Compared With Triple
Arthrodesis for Rigid Pes Planovalgus.
AB - For rigid pes planovalgus deformities, modified double and triple arthrodeses
have had high union rates and subjective outcomes reported. Increased rates of
talonavicular nonunions after modified double arthrodesis have led to concern
regarding this procedure. A retrospective medical record review was performed of
patients who had undergone either a modified double (n = 9) or triple (n = 7)
arthrodesis for stage 3 pes planovalgus deformity. Radiographs were reviewed for
hindfoot alignment, bony union, and hardware failure. Data from questionnaires,
including the Foot and Ankle Ability Measure and the Foot and Ankle Outcome
Score, were obtained. No significant differences were found between the cohorts
in terms of preoperative radiographic parameters or patient characteristics. The
modified double arthrodesis cohort demonstrated a nonunion rate of 44% (4 of 9),
but the triple arthrodesis cohort had a 0% (0 of 7) nonunion rate (p = .042). The
Foot and Ankle Ability Measure activities of daily living, Foot and Ankle Outcome
Score activities of daily living, and Foot and Ankle Outcome Score quality of
life scores were significantly worse for the modified double arthrodesis than for
the triple arthrodesis group. For patients with stage 3 pes planovalgus, modified
double arthrodesis resulted in significantly greater rates of nonunion and
incomplete union, with significantly inferior subjective outcome scores compared
with triple arthrodesis for the same indication.
PMID- 27614823
TI - A Biomechanical Comparison of 3 Different Arthroscopic Lateral Ankle
Stabilization Techniques in 36 Cadaveric Ankles.
AB - Arthroscopic lateral ankle stabilization has become an increasingly popular
option among foot and ankle surgeons to address lateral ankle instability,
because it combines a modified Brostrom-Gould procedure with the ability to
address any intra-articular pathologic findings at the same session. The present
study evaluated 3 different constructs in a cadaveric model. Thirty-six fresh
frozen cadaver limbs were used, and the anterior talofibular ligament was
identified and sectioned. The specimens were then placed into 1 of 3 groups.
Group 1 received a repair with a single-row, 2-suture anchor construct; group 2
received repair with a novel, double-row, 4-anchor knotless construct; and group
3 received repair with a double-row, 3-anchor construct. Specimens were then
tested for stiffness and load to ultimate failure using a customized jig.
Stiffness was measured in each of the groups and was 12.10 +/- 5.43 (range 5.50
to 22.24) N/mm for group 1, 13.40 +/- 7.98 (range 6.71 to 36.28) N/mm for group
2, and 12.55 +/- 4.00 (range 6.48 to 22.14) N/mm for group 3. No significant
differences were found among the 3 groups in terms of stiffness (p = .939, 1-way
analysis of variance, alpha = 0.05). The groups were tested to failure, with
observed force measurements of 156.43 +/- 30.39 (range 83.69 to 192.00) N for
group 1, 206.62 +/- 55.62 (range 141.37 to 300.29) N for group 2, and 246.82 +/-
82.37 (range 164.26 to 384.93) N for group 3. Statistically significant
differences were noted between groups 1 and 3 (p = .006, 1-way analysis of
variance, alpha = 0.05). The results of the present study have shown that a
previously reported arthroscopic lateral ankle stabilization procedure, when
modified with an additional proximal suture anchor into the fibula, results in a
statistically significant increase in strength in terms of the maximum load to
failure. Additionally, we have described a previously unreported, knotless
technique for arthroscopic lateral ankle stabilization.
PMID- 27614824
TI - Translation, Cross-Cultural Adaptation, Reliability, and Validity of Turkish
Version of the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale.
AB - We sought to translate and culturally adapt the American Orthopaedic Foot and
Ankle Society ankle-hindfoot scale (AOFAS-AHFS) into Turkish and determine the
selected psychometric properties of the translated version. The AOFAS-AHFS is
widely used to evaluate disability associated with foot and ankle injuries but
has not yet been translated or culturally adapted for Turkish-speaking
individuals. The AOFAS-AHFS was translated into Turkish using the Beaton
guidelines. The measurement properties of the Turkish AOFAS-AHFS (internal
consistency, construct validity, and floor and ceiling effects) were tested in 72
patients (94 feet, 50 [69.4%] females; average +/- SD age 44.88 +/- 16.30 years)
with a variety of foot and ankle pathologic features. Construct validity was
analyzed using the Turkish version of the Foot and Ankle Ability Measure (FAAM)
and the Medical Outcomes Study short-form 12-item survey (SF-12). The Turkish
version of the AOFAS-AHFS showed excellent test-retest reliability (intraclass
correlation coefficient 0.91). The correlation coefficients between the AOFAS
AHFS and the FAAM activities of daily living and FAAM sport were r = 0.41, p =
.01 and r = 0.37, p = .03, respectively. The correlation coefficients between the
AOFAS-AHFS and the SF-12 physical component scale was r = 0.27, p = .08. The
weakest correlation was found between the AOFAS-AHFS and the SF-12 mental
component scale (r = -0.03, p = .73). The Turkish version of the AOFAS-AHFS has
sufficient reliability and validity to measure patient-reported outcomes for
Turkish-speaking individuals with a variety of foot and ankle disorders.
PMID- 27614825
TI - Bilateral Arthrodesis of the Ankle Joint: Self-Reported Outcomes in 35 Patients
From the Swedish Ankle Registry.
AB - Bilateral ankle arthrodesis is seldom performed, and results concerning the
outcome and satisfaction can only sparsely be found in published studies. We
analyzed the data from 35 patients who had undergone bilateral ankle arthrodesis
in the Swedish Ankle Registry using patient-reported generic and region-specific
outcome measures. Of 36 talocrural arthrodeses and 34 tibio-talar-calcaneal
arthrodeses, 6 ankles (9%) had undergone repeat arthrodesis because of nonunion.
After a mean follow-up period of 47 +/- 5 (range 12 to 194) months, the mean
scores were as follows: self-reported foot and ankle score, 33 +/- 10 (range 4 to
48); the EuroQol Group's EQ-5DTM score, 0.67 +/- 0.28 (range -0.11 to 1), the
EuroQol Group's visual analog scale score, 70 +/- 19 (range 20 to 95), 36-item
Short Form Health Survey (SF-36) physical domain, 39 +/- 11 (range 16 to 58); and
SF-36 mental domain, 54 +/- 14 (range 17 to 71). Patients with rheumatoid
arthritis seemed to have similar self-reported foot and ankle scores but possibly
lower EQ-5DTM and SF-36 scores. Those with talocrural arthrodeses scored higher
than did those with tibio-talar-calcaneal arthrodeses on the EQ5DTM and SF-36
questionnaires (p = .03 and p = .04). In 64 of 70 ankles (91%), the patients were
satisfied or very satisfied with the outcome. In conclusion, we consider
bilateral ankle arthrodesis to be a reasonable treatment for symptomatic hindfoot
arthritis, with high postoperative mid-term satisfaction and satisfactory scores
on the patient-reported generic and region-specific outcome measures, when no
other treatment option is available.
PMID- 27614826
TI - A Protocol for Percutaneous Transarticular Fixation of Sanders Type II and III
Calcaneal Fractures With or Without an Added Mini-Open Approach.
AB - Intra-articular fracture of the calcaneus is one of the most displeasing
fractures if not properly managed. Open reduction and internal fixation have been
associated with a high incidence of postoperative soft tissue complications.
Closed reduction and percutaneous fixation have resulted in a greater incidence
of postoperative subtalar osteoarthritis with improper reduction of the articular
surface. In the present study, a mini-open approach was used in cases of failure
of articular surface restoration with closed reduction. A total of 64 feet in 57
consecutive patients with an intra-articular calcaneal fracture underwent the
proposed minimally invasive surgical protocol. Of the 57 patients, 7 (12.3%) had
bilateral fractures. According to Sanders classification, 33 (51.6%) fractures
were type II and 31 (48.4%) were type III. Seven (12.3%) patients had wedge
fractures of the dorsolumbar spine without neurologic manifestations. The
postoperative evaluation included radiographs and completion of the Maryland Foot
Score and visual analog scale for pain. The mean follow-up period was 16 (range
12 to 36) months. The mean operative time was 42 (range 35 to 60) minutes. The
mean period until union of the fracture was 12 (range 10 to 16) weeks. The
clinical results according to the Maryland Foot Score revealed 52 (81%) with
satisfactory (27 excellent and 25 good) and 12 (19%) with unsatisfactory (10 fair
and 2 poor) results. The mean visual analog scale score was 1.5 +/- 0.3 when
radiographic fracture healing was observed. Six patients (9.4%) developed
superficial pin tract infections that responded to local care and parenteral
antibiotic therapy and resolved completely after removal of the Kirschner wires.
In conclusion, the presented surgical protocol combining closed reduction with or
without an added mini-open approach and percutaneous fixation improves the
functional outcome and minimizes the incidence of complications.
PMID- 27614827
TI - Evaluating Blood Loss and the Effect of Antiplatelet Treatment in Foot and Ankle
Amputations.
AB - The interrelationship between diabetes mellitus and cardiovascular disease is
well-documented, and, secondary to the latter, is the use of antiplatelet
therapy. Although diabetes and the associated vascular manifestations are driving
forces behind lower extremity amputations, few data are available on the risks of
perioperative antiplatelet therapy with foot and ankle amputations. The goal of
the present study was to address the surgical effect of continuing or
discontinuing antiplatelet therapy before foot and/or ankle amputation. The
following data were retrospectively collected: blood loss, pre- and postoperative
hematocrit and hemoglobin, operative time, amputation type, age, diabetic status,
antiplatelet treatment, and number of transfusions during the perioperative
period. Perioperative antiplatelet therapy was defined as exposure to aspirin or
clopidogrel within 3 days before surgery. To compare the outcomes between groups,
the following factors were analyzed using bivariate analyses and then
multivariate regression models: (1) the need for transfusions, (2) high blood
loss (>20 mL), (3) volume of blood loss, and (4) operative time. The
noninferiority of continued antiplatelet use was assessed in terms of operative
time and blood loss, using a noninferiority margin of 10 minutes or 10 mL,
respectively. Antiplatelet therapy was not a statistically significant risk
factor for any of the studied outcomes on multivariate analysis. Equivalence
testing revealed that continuing antiplatelet therapy is not inferior to
discontinuing perioperative therapy in terms of blood loss and operative time.
Multivariate analysis of the data suggested that antiplatelet therapy has no
statistically significant impact on blood loss, transfusion rate, or operative
time.
PMID- 27614828
TI - Modification of embryonic resistance to heat shock in cattle by melatonin and
genetic variation in HSPA1L.
AB - The objectives were to test whether (1) melatonin blocks inhibition of embryonic
development caused by heat shock at the zygote stage, and (2) the frequency of a
thermoprotective allele for HSPA1L is increased in blastocysts formed from heat
shocked zygotes as compared with blastocysts from control zygotes. It was
hypothesized that melatonin prevents effects of heat shock on development by
reducing accumulation of reactive oxygen species (ROS) and that embryos
inheriting the thermoprotective allele of HSPA1L would be more likely to survive
heat shock. Effects of 1 uM melatonin on ROS were determined in experiments 1 and
2. Zygotes were cultured at 38.5 or 40 degrees C for 3 h in the presence of
CellROX reagent (ThermoFisher Scientific, Waltham, MA). Culture was in a low [5%
(vol/vol)] oxygen (experiment 1) or low or high [21% (vol/vol)] oxygen
environment (experiment 2). Heat shock and high oxygen increased ROS; melatonin
decreased ROS. Development was assessed in experiments 3 and 4. In experiment 3,
zygotes were cultured in low oxygen +/- 1 uM melatonin and exposed to 38.5 or 40
degrees C for 12 h (experiment 1) beginning 8 h after fertilization. Melatonin
did not protect the embryo from heat shock. Experiment 4 was performed similarly
except that temperature treatments (38.5 or 40 degrees C, 24 h) were performed in
a low or high oxygen environment (2*2 * 2 factorial design with temperature,
melatonin, and oxygen concentration as main effects), and blastocysts were
genotyped for a deletion (D) mutation (C->D) in the promoter region of HSPA1L
associated with thermotolerance. Heat shock decreased percent of zygotes
developing to the blastocyst stage independent of melatonin or oxygen
concentration. Frequency of genotypes for HSPA1L was affected by oxygen
concentration and temperature, with an increase in the D allele for blastocysts
that developed in high oxygen and following heat shock. It was concluded that (1)
lack of effect of melatonin or oxygen concentration on embryonic development
means that the negative effects of heat shock on the zygote are not mediated by
ROS, (2) previously reported effect of melatonin on fertility of heat-stressed
cows might involve actions independent of the antioxidant properties of
melatonin, and (3) the deletion mutation in the promoter of HSPA1L confers
protection to the zygote from heat shock and high oxygen. Perhaps, embryonic
survival during heat stress could be improved by selecting for thermotolerant
genotypes.
PMID- 27614829
TI - Technical note: The use of an accelerometer for measuring step activity and lying
behaviors in dairy calves.
AB - Calf behaviors such as step activity, lying bouts, and lying time may be an
indicator of calf health and welfare. To reduce time-consuming visual
observations, the use of behavioral monitoring systems have been developed to
capture these data. Previous studies have validated lying behaviors using an
accelerometer (HPG; HOBO Pendant G data logger, Onset Computer Corp., Bourne, MA)
in calves. However, the HPG does not measure step activity. The objectives of
this study were to (1) validate step activity, lying bouts, and lying time of
AfiTag II (AT2; AfiTag II, Afimilk Ltd., Kibbutz Afikim, Israel) to observations
from video, and (2) to compare the behavioral data from AT2 to the HPG. Calves
(n=5) were group housed with an automatic calf feeder. Video cameras were
installed at both sides of the pen, and observations were analyzed for 7h/calf.
The AT2 and the HPG were both attached to the lateral side of the right rear leg
of 5 calves, and data were recorded for 10 d. The full 10-d data set was used to
examine correlations for lying bouts and lying time between AT2 and the HPG. The
HPG was set at a 60-s sampling interval and the output was analyzed both
unfiltered as well as utilizing a 1-min event filter to remove potentially
erroneous readings. The AT2 recorded step activity, lying bouts, and lying time,
and summarized these behaviors in 15-min periods. The AT2 recorded lying time in
3-min intervals, which were then automatically summarized in 15-min periods. The
correlations of step activity, lying bouts, and lying time between video
recordings and AT2 were 0.99. For the second objective, correlations between AT2
and the HPG were 0.99 for lying time and 0.93 for lying bouts. The 1-min event
filter resulted in a 0.03 improvement in correlations for lying bouts between the
HPG and AT2. The high correlation between video recordings and AT2 suggest that
this device can be used to measure step activity, lying time, and lying bouts in
unweaned dairy calves housed in groups.
PMID- 27614830
TI - Genetic parameters of subclinical macromineral disorders and major clinical
diseases in postparturient Holstein cows.
AB - The main objective of this study was to assess the genetic parameters of
subclinical disorders associated with subclinical hypocalcemia, hypophosphatemia,
subclinical hypomagnesemia, hypokalemia, and hyperphosphatemia, as well as major
clinical diseases after calving in Holstein cows. The secondary objective was to
estimate the associated genetic and phenotypic correlations among these
subclinical and clinical conditions after calving in Holstein cows. The study was
conducted in 9dairy herds located in Northern Greece. None of the herds used any
kind of preventive measures for milk fever (MF). A total of 1,021 Holstein cows
with pedigree information were examined from November 2010 until November 2012.
The distribution across parities was 466 (parity 1), 242 (parity 2), 165 (parity
3), and 148 (parity 4 and above) cows. All cows were subjected to a detailed
clinical examination and blood was sampled on d 1, 2, 4, and 8 after calving.
Serum concentrations of Ca, P, Mg, and K were measured in all samples, whereas
beta-hydroxybutyrate (BHB) was measured only for d 8. The final data set included
4,064 clinical and 16,848 biochemical records (4,020 Ca, 4,019 P, 4,020Mg,
3,792K, and 997 BHB). Data of 1,988 observations of body condition score at d 1
and 8 were also available. All health traits were analyzed with a univariate
random regression model. The genetic analysis for macromineral-related disorders
included 986 cows with no obvious signs of MF (35 cows with MF were excluded).
Analysis for other health traits included all 1,021 cows. A similar single record
model was used for the analysis of BHB. Genetic correlations among traits were
estimated with a series of bivariate analyses. Statistically significant daily
heritabilities of subclinical hypocalcemia (0.13-0.25), hypophosphatemia (0.18
0.33), subclinical hypomagnesemia (0.11-0.38), and hyperphosphatemia (0.14-0.22)
were low to moderate, whereas that of hypokalemia was low (0.08-0.10). The
heritability of body condition score was 0.20+/-0.10. Statistically significant
daily heritabilities of clinical diseases were those of MF (0.07-0.11), left
displaced abomasum (0.19-0.31), and mastitis (0.15-0.41). Results suggest that
these health disorders are heritable traits and could be minimized with proper
genetic selection. Statistically significant phenotypic correlations were
estimated for the first time between macromineral concentrations and almost all
transition cow metabolic and infectious health disorders.
PMID- 27614831
TI - Peripartal rumination dynamics and health status in cows calving in hot and cool
seasons.
AB - Our objective was to evaluate the effect of season of calving, associated with
variable levels of heat stress, on the dynamics of rumination during the
prepartum period and early lactation of cows that were healthy or affected by
peripartal health disorders. Three weeks before the estimated due date, 210
multiparous Holstein cows at the University of Florida Dairy Unit were affixed
with a neck collar containing rumination loggers, providing rumination time (RT)
in 2-h periods. One blood sample was collected in a subpopulation of cows (n=76)
at 12 to 48h postcalving to assess metabolic status by determining serum calcium,
nonesterified fatty acid, and beta-hydroxybutyrate concentrations. The occurrence
of peripartal health disorders (dystocia, clinical ketosis, clinical
hypocalcemia, metritis, and mastitis) was assessed by University of Florida
veterinarians and trained farm personnel. We analyzed the dynamics of daily RT
over +/- 14d relative to parturition in cows that were healthy or affected by
specific health disorders by season of calving [hot season, June to September
(n=77); cool season, November to April (n=118)] using repeated measures analysis
and comparison of least squares means at different time points relative to
calving. Rumination was consistently reduced on the day of calving in both
healthy and sick cows in both the hot and cool seasons. Only hot-season calvings
had shorter average daily RT prepartum and postpartum in cows affected by severe
negative energy balance and subclinical ketosis. Dystocia during the hot season
was associated with shorter daily RT prepartum; for cool-season calvings, cows
with dystocia had reduced RT postpartum. We also observed reduced RT in cows with
ketosis prepartum and postpartum in both the hot and cool seasons. Daily RT was
reduced postpartum in cows with hypocalcemia and mastitis that calved during the
cool season, and it was shorter in cows with metritis in both the hot and cool
seasons. Our results indicated that the effect of heat stress on changes in
rumination patterns around calving for sick cows depends on the specific health
disorder or metabolic condition.
PMID- 27614832
TI - Short communication: On recognizing the proper experimental unit in animal
studies in the dairy sciences.
AB - Sound design of experiments combined with proper implementation of appropriate
statistical methods for data analysis are critical for producing meaningful
scientific results that are both replicable and reproducible. This communication
addresses specific aspects of design and analysis of experiments relevant to the
dairy sciences and, in so doing, responds to recent concerns raised in a letter
to the editor of the Journal of Dairy Science regarding journal policy for
research publications on pen-based animal studies. We further elaborate on points
raised, rectify interpretation of important concepts, and show how aspects of
statistical inference and elicitation of research conclusions are affected.
PMID- 27614833
TI - Evaluation of serum protein-based arrival formula and serum protein supplement
(Gammulin) on growth, morbidity, and mortality of stressed (transport and cold)
male dairy calves.
AB - Previous studies with calves and other species have provided evidence that blood
serum-derived proteins and fructooligosaccharides (FOS) may benefit intestinal
health. We assessed the effects of supplementing products containing serum
proteins as a component of arrival fluid support or serum proteins plus FOS (in
addition to additional solids, minerals, and vitamins) in an early life dietary
supplement on performance, morbidity, and mortality of stressed (transport, cold)
male calves. Male Holstein calves (n=93) <1 wk old were stratified by arrival
body weight (BW) and plasma protein concentration, and then randomly assigned to
1 of 4 treatment groups in a 2*2 factorial arrangement of one-time administration
of fluid support [either control electrolyte solution (E) or the serum protein
containing arrival formula (AF)] and 14d of either no supplementation (NG) or
supplementation with Gammulin (G; APC Inc., Ankeny, IA), which contains serum
proteins and FOS in addition to other solids, minerals, and vitamins. Upon
arrival at the research facility, calves were orally administered either AF or E.
At the next feeding, half of the calves from each fluid support treatment
received either milk replacer (20% crude protein, 20% fat) or the same milk
replacer supplemented with G (50g/d during the first 14d). Starter and water were
freely available. Feed offered and refused was recorded daily. Calf health was
assessed by daily assignment of fecal and respiratory scores. Stature measures
and BW were determined weekly. Blood samples were obtained at d 0 (before
treatments), 2, 7, 14, and 28. Calves were weaned at d 42 and remained in the
experiment until d 56. After 2 wk of treatments, calves previously fed AF had
greater body length (66.6 vs. 66.0cm), intakes of dry matter (38.7 vs. 23.5g/d)
and crude protein (9.2 vs. 5.6g/d) from starter, and cortisol concentration in
blood (17.0 vs. 13.9 ng/mL) than calves fed E. Supplementation with G resulted in
greater BW gain during the first 2 wk, increased intakes of dry matter and CP,
and decreased respiratory scores. For the 8-wk experiment, G supplementation
resulted in lower mean fecal score (1.6 vs. 1.8) and fewer antibiotic treatments
per calf (1.5 vs. 2.5) than NG. Survival was greater in G than in NG calves (98
vs. 84%). Despite the marked reduction in morbidity and mortality, blood
indicators of acute-phase response, urea N, and total protein were not affected
by AF or G in transported cold-stressed male calves.
PMID- 27614834
TI - Short communication: Variations in major mineral contents of Mediterranean
buffalo milk and application of Fourier-transform infrared spectroscopy for their
prediction.
AB - The aims of this study were (1) to assess variability in the major mineral
components of buffalo milk, (2) to estimate the effect of certain environmental
sources of variation on the major minerals during lactation, and (3) to
investigate the possibility of using Fourier-transform infrared (FTIR)
spectroscopy as an indirect, noninvasive tool for routine prediction of the
mineral content of buffalo milk. A total of 173 buffaloes reared in 5 herds were
sampled once during the morning milking. Milk samples were analyzed for Ca, P, K,
and Mg contents within 3h of sample collection using inductively coupled plasma
optical emission spectrometry. A Milkoscan FT2 (Foss, Hillerod, Denmark) was used
to acquire milk spectra over the spectral range from 5,000 to 900 wavenumber/cm.
Prediction models were built using a partial least square approach, and cross
validation was used to assess the prediction accuracy of FTIR. Prediction models
were validated using a 4-fold random cross-validation, thus dividing the
calibration-test set in 4 folds, using one of them to check the results
(prediction models) and the remaining 3 to develop the calibration models.
Buffalo milk minerals averaged 162, 117, 86, and 14.4mg/dL of milk for Ca, P, K,
and Mg, respectively. Herd and days in milk were the most important sources of
variation in the traits investigated. Parity slightly affected only Ca content.
Coefficients of determination of cross-validation between the FTIR-predicted and
the measured values were 0.71, 0.70, and 0.72 for Ca, Mg, and P, respectively,
whereas prediction accuracy was lower for K (0.55). Our findings reveal FTIR to
be an unsuitable tool when milk mineral content needs to be predicted with high
accuracy. Predictions may play a role as indicator traits in selective breeding
(if the additive genetic correlation between FTIR predictions and measures of
milk minerals is high enough) or in monitoring the milk of buffalo populations
for dairy industry purposes.
PMID- 27614835
TI - Identification of a haplotype associated with cholesterol deficiency and
increased juvenile mortality in Holstein cattle.
AB - Over the last decades, several genetic disorders have been discovered in cattle.
However, the genetic background of disorders in calves is less reported.
Recently, German cattle farmers reported on calves from specific matings with
chronic diarrhea and retarded growth of unknown etiology. Affected calves did not
respond to any medical treatment and died within the first months of life. These
calves were underdeveloped in weight and showed progressive and severe emaciation
despite of normal feed intake. Hallmark findings of the blood biochemical
analysis were pronounced hypocholesterolemia and deficiency of fat-soluble
vitamins. Results of the clinical and blood biochemical examination had striking
similarities with findings reported in human hypobetalipoproteinemia. Postmortem
examination revealed near-complete atrophy of the body fat reserves including the
spinal canal and bone marrow. To identify the causal region, we performed a
genome-wide association study with 9 affected and 21,077 control animals
genotyped with the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA),
revealing a strong association signal on BTA 11. Subsequent autozygosity mapping
identified a disease-associated haplotype encompassing 1.01 Mb. The segment of
extended homozygosity contains 6 transcripts, among them the gene APOB, which is
causal for cholesterol disorders in humans. However, results from multi-sample
variant calling of 1 affected and 47 unaffected animals did not detect any
putative causal mutation. The disease-associated haplotype has an important
adverse effect on calf mortality in the homozygous state when comparing survival
rates of risk matings vs. non-risk matings. Blood cholesterol values of animals
are significantly associated with the carrier status indicating a codominant
inheritance. The frequency of the haplotype in the current Holstein population
was estimated to be 4.2%. This study describes the identification and phenotypic
manifestation of a new Holstein haplotype characterized by pronounced
hypocholesterolemia, chronic emaciation, growth retardation, and increased
mortality in young cattle, denominated as cholesterol deficiency haplotype. Our
genomic investigations and phenotypic examinations provide additional evidence
for a mutation within the APOB gene causing cholesterol deficiency in Holstein
cattle.
PMID- 27614837
TI - Survey of bovine colostrum quality and hygiene on northern Victorian dairy farms.
AB - One of the major challenges for dairy producers is to produce, harvest, and store
high-quality colostrum and feed it to their replacement heifer calves. Limited
published data are available in Australia regarding the relationship between
colostrum management, hygiene, and quality. The objectives of this study were to
investigate (1) the colostrum storage and handling practices carried out on farm;
(2) the immunoglobulin concentration and bacterial composition of colostrum being
fed to replacement dairy heifer calves; (3) the percentage of colostrum being fed
to replacement dairy heifer calves that meet industry recommendations; and (4)
risk factors for bacterial contamination of colostrum. The study was carried out
on 24 dairy farms located near Rochester, Victoria, Australia. Two hundred forty
colostrum samples were collected (10 samples per farm). Each farm harvested and
stored first-milking colostrum under normal farm conditions. A 10-mL sample of
the colostrum was collected in a sterile container immediately before feeding,
and a Brix refractometer reading was taken. The samples were then frozen at -4
degrees C and submitted for bacterial concentration analysis. Fifty-eight percent
of colostrum samples met the recommended industry standard of a total plate count
(TPC) of <100,000cfu/mL, and 94% of colostrum samples met the recommended
industry standard of total coliform count (TCC) of 10,000cfu/mL. However, when
all the current industry recommendations for TPC, TCC, and Brix refractometer
percentage for colostrum quality were considered, only 23% of the samples met all
standards. These findings demonstrate that a large number of calves were at risk
of receiving colostrum of poor quality, with high bacterial loads that may have
interfered with the acquisition of transfer of passive immunity and affected calf
health. Further investigation is required to identify the farm-specific factors
that may influence the level of bacterial contamination of colostrum.
Recommendations as a result of this study include refrigeration of excess
colostrum shortly (within 1h) after collection and thorough disinfection of the
calf feeding apparatus before use.
PMID- 27614836
TI - Changes in fibroblast growth factor 9 mRNA in granulosa and theca cells during
ovarian follicular growth in dairy cattle.
AB - Fibroblast growth factor 9 (FGF9) has been suggested to act as an
antidifferentiation factor in cattle by reducing steroidogenesis and increasing
cell proliferation in granulosa (GC) and theca (TC) cells. The objective of this
study was to characterize FGF9 mRNA abundance in GC and TC during development of
dominant follicles in dairy cattle. Estrous cycles of nonlactating dairy cattle
were synchronized, and ovaries were collected on either d 3 to 4 (n=8) or 5 to 6
(n=8) postovulation for GC and TC RNA extraction from small (1-5mm), medium (5.1
8mm), and large (8.1-18mm) follicles for PCR analysis. The FGF9 mRNA abundance
was greater in GC than in TC. In GC, FGF9 mRNA abundance was greater in small,
medium, and large estrogen-inactive [i.e., concentrations of estradiol
(E2)P4) follicles at both early (d 3-4) and late (d 5-6) growing phases of
first dominant follicle. Abundance of FGF9 mRNA increased in medium-sized
follicles from early to late growing phase of the dominant follicle. In TC, FGF9
mRNA abundance was greater in large E2-inactive follicles than in large E2-active
follicles on d 3 to 4 postovulation; no significant differences in TC FGF9 mRNA
existed among follicle types on d 5 to 6 postovulation. Correlations among levels
of follicular fluid hormones and FGF9 mRNA levels revealed significant negative
correlations between GC FGF9 mRNA abundance and follicular fluid E2 (r=-0.68),
free IGF-1 (r=-0.63), and E2-to-P4 ratio (r=-0.58). In summary, abundance of FGF9
mRNA in GC and TC increases in medium-sized follicles during development of
dominant follicles and is less in dominant E2-active than subordinate E2-inactive
follicles, suggesting that FGF9 signaling could contribute to normal follicle
development and steroidogenesis in dairy cattle.
PMID- 27614838
TI - Gamma delta T cells are early responders to Mycobacterium avium ssp.
paratuberculosis in colostrum-replete Holstein calves.
AB - Peripheral blood mononuclear cells (PBMC) and mesenteric node lymphocytes (MNL)
were obtained from 30 calves that were assigned randomly at birth to 1 of 6
treatment groups with 5 calves per treatment in a 14-d study: (1) colostrum
deprived (CD), no vitamins; (2) colostrum-replacer (CR), no vitamins; (3) CR,
vitamin A; (4) CR, vitamin D3; (5) CR, vitamin E; (6) CR, vitamins A, D3, E.
Calves were injected with appropriate vitamin supplements and fed pasteurized
whole milk (CD calves) or fractionated colostrum replacer (CR calves) at birth.
Thereafter, all calves were fed pasteurized whole milk fortified with vitamins
according to treatment group. Calves were orally inoculated with 108 cfu of
Mycobacterium avium ssp. paratuberculosis (MAP) on d 1 and 3. The PBMC and MNL
harvested on d 13 were analyzed by flow cytometry as fresh cells, after 3-d
culture with phytohemagglutinin (PHA), and after 6-d culture with a whole-cell
sonicate of MAP (MPS). Peripheral gammadelta T cells were a predominant
lymphocyte subset in neonatal calves, with a decreased percentage noted in CD
calves compared with CR calves. As well, CD25 expression was higher in gammadelta
T cells compared with other cell subsets, regardless of treatment group.
Stimulation of PBMC with PHA resulted in increased CD4+ and CD8+ subsets, whereas
MNL response was dominated by expansion of B-cell subpopulations. Stimulation
with PHA and MPS decreased the relative abundance of PBMC gammadelta T cells, but
MNL gammadelta T cells increased upon stimulation with MPS. These results
identify gammadelta T cells as key early responders to intracellular infection in
neonatal calves and suggest that colostrum may be an important mediator of this
response.
PMID- 27614839
TI - Milk yield, milk composition, and hepatic lipid metabolism in transition dairy
cows fed flaxseed or linola.
AB - The response of transition dairy cows to dietary supplementation with fat sources
of various fatty acid profiles could affect hepatic fat metabolism differently.
Twenty-eight Holstein cows were blocked for similar calving date 4wk before
expected parturition to compare the effects of feeding sources of n-3 and n-6
fatty acids on milk production and composition, plasma metabolites, and liver
parameters. Cows within each block were assigned to 1 of 3 isonitrogenous and
isoenergetic diets: control with a source of calcium salts of palm oil (MEG; 1.1
and 2.6% of the dry matter in prepartum and postpartum diets, respectively); n-3
fatty acids supplied as whole flaxseed (WFL; 4.8 and 7.7% of the dry matter in
prepartum and postpartum diets, respectively); and n-6 fatty acids supplied as
whole linola (WLO; 4.8 and 7.7% of the dry matter in prepartum and postpartum
diets, respectively). Diets were fed until wk 14 of lactation. Contrasts of WFL
versus WLO and polyunsaturated fatty acids versus MEG were compared. Cows fed
polyunsaturated fatty acids increased dry matter intake over time at a greater
extent than those fed MEG, which resulted in enhanced energy balance. Cows fed
MEG produced more milk compared with those fed polyunsaturated fatty acids, and
there was no difference between those fed WFL and WLO. We found no effect on body
condition score and body weight. Plasma concentrations of glucose, fatty acids,
and BHB were similar among diets. There was no effect of diet on concentration of
glycogen and activities of superoxide dismutase and glutathione peroxidase in the
liver. We observed higher concentrations of hepatic lipids and triacylglycerol in
cows fed MEG compared with those fed polyunsaturated fatty acids, and no
difference between WFL and WLO. Hepatic catalase activity tended to be higher on
wk 4 after calving for cows supplemented with WFL compared with those fed WLO.
Feeding linoleic and linolenic acids as unprotected oilseeds increased dry matter
intake over time at a greater extent for cows fed MEG, improved the energy
status, and lowered hepatic lipids and triacylglycerol contents, which may
contribute to enhance the health status of transition dairy cows.
PMID- 27614840
TI - Sterol regulatory element-binding proteins are regulators of the sodium/iodide
symporter in mammary epithelial cells.
AB - The sodium/iodide symporter (NIS), which is essential for iodide concentration in
the thyroid, is reported to be transcriptionally regulated by sterol regulatory
element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly
activated after parturition and throughout lactation in the mammary gland of
cattle and are important for mammary epithelial cell synthesis of milk lipids. In
this study, we tested the hypothesis that the NIS gene is regulated also by SREBP
in mammary epithelial cells, in which NIS is functionally expressed during
lactation. Regulation of NIS expression and iodide uptake was investigated by
means of inhibition, silencing, and overexpression of SREBP and by reporter gene
and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell
line, a breast adenocarcinoma cell line, which shows inducible expression of NIS
by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is
widely used to investigate the regulation of mammary gland NIS and NIS-specific
iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25
hydroxycholesterol (5 uM) for 48h reduced ATRA (1 uM)-induced mRNA concentration
of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP
1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration
of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of
nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7
cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter
gene experiments with varying length of NIS promoter reporter constructs revealed
that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2
approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP
binding motif (SRE) at -38 relative to the transcription start site of the NIS
gene. Gel shift assays using oligonucleotides spanning either the wild-type or
the mutated SRE at -38 of the NIS 5'-flanking region showed that in vitro
translated nSREBP-1c and nSREBP-2 bind only the wild-type but not the mutated SRE
at -38 of NIS. Collectively, the present results from cell culture experiments
with human mammary epithelial MCF-7 cells and from genetic studies show for the
first time that the NIS gene and iodide uptake are regulated by SREBP in cultured
human mammary epithelial cells. Future studies are necessary to clarify if the
regulation of NIS expression and iodide uptake by SREBP also applies to the
lactating bovine mammary epithelium.
PMID- 27614841
TI - Short communication: Association of foot and leg conformation and body weight
with claw disorders in Spanish Holstein cows.
AB - Data of first-lactation Holstein cows including claw disorders, foot and leg type
traits, and structure and capacity type traits were used to study the phenotypic
association of conformation and body weight with claw health status. The claw
disorders studied were digital and interdigital dermatitis, sole ulcer, white
line disease, and an overall claw disorder trait, indicating the presence of any
of the 6 claw disorders recorded by the Spanish I-SAP program. Body weight was
estimated indirectly with the Von Bertalanffy equation using live weight, which
was also estimated from body depth, stature, and chest width. Cows with poor
scores for foot and leg traits were more likely to have a claw disorder, with the
exception of rear leg rear view and foot and leg composite that did not show any
association with the studied disorders. The heavier the cow was, the higher was
the probability of having sole ulcer, white line disease, or overall claw
disorder trait, but digital and interdigital dermatitis, as an infectious
disorder, did not show any association with body weight. Therefore, it is
recommended that the preventive trimming routine be improved, which means
checking each cow at least once per lactation and trimming if necessary, to
achieve balanced weight-bearing for heavier cows and cows with poor feet and leg
classification.
PMID- 27614842
TI - Short communication: Pasteurization as a means of inactivating staphylococcal
enterotoxins A, B, and C in milk.
AB - Our aim was to assess the effect of pasteurization temperature on inactivation of
staphylococcal enterotoxins (SE). Milk samples were inoculated with log 4.38 to
5.18cfu/mL of 40 different Staphylococcus aureus strains having the ability to
produce types A, B, or C SE and incubated at 37 degrees C for 24h to develop SE.
This incubation was followed by heat treatment for 15 s at 72, 85, and 92 degrees
C. Samples were analyzed for Staph. aureus count by plate method and,
specifically, for SE presence. An enzyme-linked immunofluorescent assay on a
MiniVIDAS analyzer (bioMerieux, Marcy l'Etoile, France) was used to detect SE,
which were determined semiquantitatively based on test values. The Staph. aureus
count in milk before pasteurization did not affect the amount of SE. Before
pasteurization, SEB was detected in the lowest amount compared with other SE
types. Staphylococcal enterotoxins were markedly reduced with pasteurization and
inactivated at pasteurization temperatures to an extent depending on the amount
in the sample before pasteurization. After pasteurization at 72 degrees C, SE
were detected in 87.5% of samples (35/40), after pasteurization at 85 degrees C
in 52.5% of samples (21/40), and after pasteurization at 92 degrees C in 45.0% of
samples (18/40). We determined that SE may still persist in milk even when Staph.
aureus bacteria are inactivated through pasteurization. Although pasteurization
may partially inactivate SE in milk, a key measure in the prevention of
staphylococcal enterotoxicosis linked to pasteurized milk consumption is to avoid
any cold chain disruption during milk production and processing.
PMID- 27614843
TI - Prediction of portal and hepatic blood flow from intake level data in cattle.
AB - Interest is growing in developing integrated postabsorptive metabolism models for
dairy cattle. An integral part of linking a multi-organ postabsorptive model is
the prediction of nutrient fluxes between organs, and thus blood flow. The
purpose of this paper was to use a multivariate meta-analysis approach to model
portal blood flow (PORBF) and hepatic venous blood flow (HEPBF) simultaneously,
with evaluation of hepatic arterial blood flow (ARTBF; ARTBF=HEPBF - PORBF) and
PORBF/HEPBF (%) as calculated values. The database used to develop equations
consisted of 296 individual animal observations (lactating and dry dairy cows and
beef cattle) and 55 treatments from 17 studies, and a separate evaluation
database consisted of 34 treatment means (lactating dairy cows and beef cattle)
from 9 studies obtained from the literature. Both databases had information on
dry matter intake (DMI), metabolizable energy intake (MEI), body weight, and a
basic description of the diet including crude protein intake and forage
proportion of the diet (FP; %). Blood flow (L/h or L/kg of BW0.75/h) and either
DMI or MEI (g or MJ/d or g or MJ/kg of BW0.75/d) were examined with linear and
quadratic fits. Equations were developed using cow within experiment and
experiment as random effects, and blood flow location as a repeated effect. Upon
evaluation with the evaluation database, equations based on DMI typically
resulted in lower root mean square prediction errors, expressed as a % of the
observed mean (rMSPE%) and higher concordance correlation coefficient (CCC)
values than equations based on MEI. Quadratic equation terms were frequently
nonsignificant, and the quadratic equations did not outperform their linear
counterparts. The best performing blood flow equations were PORBF (L/h)=202 (+/
45.6) + 83.6 (+/-3.11) * DMI (kg/d) and HEPBF (L/h)=186 (+/-45.4) + 103.8 (+/
3.10) * DMI (kg/d), with rMSPE% values of 17.5 and 16.6 and CCC values of 0.93
and 0.94, respectively. The residuals (predicted - observed) for PORBF/HEPBF were
significantly related to the forage % of the diet, and thus equations for PORBF
and HEPBF based on forage and concentrate DMI were developed: PORBF (L/h)=210 (+/
51.0) + 82.9 (+/-6.43) * forage (kg of DM/d) + 82.9 (+/-6.04) * concentrate (kg
of DM/d), and HEPBF (L/h)=184 (+/-50.6) + 92.6 (+/-6.28) * forage (kg of DM/d) +
114.2 (+/-5.88) * concentrate (kg of DM/d), where rMSPE% values were 17.5 and
17.6 and CCC values were 0.93 and 0.94, respectively. Division of DMI into forage
and concentrate fractions improved the joint Bayesian information criterion value
for PORBF and HEPBF (Bayesian information criterion=6,512 vs. 7,303), as well as
slightly improved the rMSPE and CCC for ARTBF and PORBF/HEPBF. This was despite
minimal changes in PORBF and HEPBF predictions. Developed equations predicted
blood flow well and can easily be used within a postabsorptive model of nutrient
metabolism. Results also suggest different sensitivity of PORBF and HEPBF to the
composition of DMI, and accounting for this difference resulted in improved ARTBF
predictions.
PMID- 27614844
TI - MyD88 modulates eosinophil and neutrophil recruitment as well as IL-17A
production during allergic inflammation.
AB - The contribution of dysregulated innate immune responses to the pathogenesis of
allergic disease remains largely unknown. Herein, we addressed the role of Toll
like receptor signaling in airway inflammation by studying mice rendered
deficient for the myeloid differentiation factor 88 (MyD88-/-) which results in
concurrent deficiencies in TLR and IL-1R1 signaling pathways. We show that the
lack of MyD88 offers a partial protection from allergic disease evidenced by
reduced airway eosinophilia and production of the Th17-associated effector
cytokine IL-17A. By contrast, airway hyperreactivity and Th2 cytokine production,
the cardinal features of allergic disease, remained unchanged. We found that the
impaired IL-17A production in MyD88-/- mice was associated with defective CD4+ T
cells, which failed to respond to IL-23 stimulation. The total number of Th17
associated effectors in lymph nodes was likewise decreased. Taken together, our
results demonstrate that MyD88-dependent mechanisms are critical for
orchestrating lung inflammatory responses, in terms of IL-17A production, as well
as eosinophil and neutrophil recruitment.
PMID- 27614845
TI - Transgenic T cell-specific expression of CXCR3 enhances splenic and hepatic T
cell accumulation but does not affect the outcome of visceral leishmaniasis.
AB - The outcome of visceral leishmaniasis, caused by parasite Leishmania donovani,
depends on the recruitment of leishmanicidal Th1 cells. Chemokine receptor CXCR3,
preferentially expressed by Th1 cells, is critical for migration of these T cells
during infection. During chronic VL, there is a decrease in the presence of CXCR3
expressing CD4+ T cells in the spleen, which is associated with high parasitic
burden in this organ. We therefore examined whether T cell-specific expression of
CXCR3 in mice (CXCR3Tg) would promote resistance to VL. L. donovani infected
CXCR3Tg mice showed increased accumulation of T cells in the spleens compared to
WT littermates (CXCR3+/+). However, CXCR3+ T cells from CXCR3Tg mice showed low
CD69 expression and these mice developed fewer granulomas. Additionally, both
groups of mice showed similar cytokine profiles and parasitic burdens during the
course of infection. In summary, although T cell-specific expression of CXCR3
promoted the accumulation of CXCR3-expressing T cells during L. donovani
infection, this did not enhance resistance to VL.
PMID- 27614846
TI - Cellular and molecular mechanisms of immune dysregulation and autoimmunity.
AB - Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that
affect the function of the immune system. A specific group of PIDs entitled
"diseases of immune dysregulation" are developed due to mutation in the genes
which have critical roles in the regulation of immune responses and immunological
tolerance. This group of PID patients develop autoimmune and inflammatory
disorders as a result of their impaired immunity, therefore they could be
considered as a model for analyzing the link between immune dysregulation and
autoimmunity. In this article, our aim is to describe the function of the mutated
gene, the molecular and cellular mechanisms underlying the immune dysregulation
and review the literature in regard with the reported autoimmune disorders in the
main types of immunodysregulatory diseases including genetic defects of
regulatory T cells, familial hemophagocytic lymphohistiocytosis syndromes,
autoimmunity without lymphoproliferation, autoimmune lymphoproliferative
syndrome, immune dysregulation with colitis, and type 1 interferonopathies.
PMID- 27614848
TI - Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent
Angioscopy and Microscopy.
AB - Native triglycerides (TG) deposited in the human vascular wall is not measurable
or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm
and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid
monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just
TG. Therefore, localization of TG in coronary plaques and normal segments that
were obtained from 19 human autopsy cases was examined by color fluorescent
angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG. By CFA, the
percentage (%) incidence of TG in 23 normal segments, 13 white plaques without
lipid deposition, 18 white plaques (growth stage) with lipid deposition, 11
yellow plaques without necrotic core (mature stage), and 12 yellow plaques with
necrotic core (advanced mature stage) was 95, 92, 50, 27, and 25, respectively.
By color fluorescent microscopy, TG deposited mostly in the fibrotic area of the
plaques. Contrary to the general belief that TG amount increases with plaque
maturation, the results indicated that TG was deposited in most of the normal
coronary segments, but the amount decreased with plaque maturation. If 3-ANA
becomes applicable clinically, the CFA system could be used for imaging TG within
coronary plaques in patients in vivo.
PMID- 27614847
TI - Photodynamic performance of zinc phthalocyanine in HeLa cells: A comparison
between DPCC liposomes and BSA as delivery systems.
AB - Comparable intracellular concentrations (~30pmol/10(6) cells) of bovine serum
albumin-ZnPc (BSA) adduct outperformed dipalmitoyl-phosphatidyl-choline (DPPC)
liposomes containing ZnPc at photodynamic-killing of human cervical cancer cells
(HeLa) after only 15min of irradiation using red light (lambda>620nm, 30W/cm(2)).
This result could not be simply explained in terms of dye aggregation within the
carrier, since in the liposomes the dye was considerably less aggregated than in
bovine serum albumin, formulation that was capable to induce cell apoptosis upon
red light exposure. Thus, using specific organelle staining, our cumulative data
points towards intrinsic differences in intra-cellular localization depending on
the cargo vehicle used, being ZnPc:BSA preferentially located in the near
vicinity of the nucleus and in the Golgi structures, while the liposomal
formulation ZnPc:DPPC was preferentially located in cellular membrane and
cytoplasm. In addition to those differences, using real-time advanced
fluorescence lifetime imaging of HeLa cells loaded with the photosensitizer
contained in the different vehicles, we have found that only for the ZnPc:BSA
formulation, there was no significant changes in the fluorescence lifetime of the
photosensitizer inside the cells. This contrasts with the in situ~two-fold
reduction of the fluorescence lifetime measured for the liposomal ZnPc
formulation. Those observations point towards the superiority of the protein to
preserve dye aggregation, and its photochemical activity, post-cell uptake,
demonstrating the pivotal role of the delivery vehicle at determining the
ultimate fate of a photosensitizer.
PMID- 27614850
TI - Prognostic Value of Late Gadolinium Enhancement in Nonischemic Cardiomyopathy.
AB - The purpose of this study was to determine the prognostic value of late
gadolinium enhancement seen on cardiac magnetic resonance (CMR) imaging in
patients with nonischemic cardiomyopathy (NICMP). Patients with NICMP are at
increased risk for cardiovascular events and death. The presence of late
gadolinium enhancement (LGE) in CMR may be associated with a poor prognosis, but
its significance is still under investigation. We retrospectively studied 105
consecutive patients with NICMP and left ventricular ejection fraction (LVEF)
<=40% referred for CMR. The cohort was analyzed for the presence of LGE and left
and right ventricular functional parameters. Patients were followed for the
composite end point of hospitalization for congestive heart failure, appropriate
implantable cardioverter-defibrillator therapy, or all-cause mortality. LGE was
observed in 68% (n = 71) of the cohort. Both groups were similar in age, LVEF and
LV end-diastolic volume. The LGE+ patients were more often men and had larger
right ventricular volumes. At a mean follow-up of 806 +/- 582 days, there were 26
patients (23 in the LGE+ group) who reached the primary end point. Event-free
survival was significantly worse for the LGE+ patients. After adjusting for
traditional risk factors (age, gender, and LVEF), patients with LGE had an
increased risk of experiencing the primary end point (hazard ratio 4.47, 95% CIs
1.27 to 15.74, p = 0.02). The presence of LGE in patients with NICMP strongly
predicts the occurrence of adverse events. In conclusion, this may be important
in risk stratification and management.
PMID- 27614849
TI - Nonenzymatic Mechanism of Statins in Modulating Cholesterol Particles Formation.
AB - Statin drugs are leading medication prescribed for treatment of dyslipidemic
patients aimed at preventing both primary and secondary incidences of
atherosclerosis-related cardiovascular events. Statin drugs competitively inhibit
HMG-CoA reductase enzyme activity, thereby inhibiting cell-mediated cholesterol
synthesis and reducing the low-density lipoprotein (LDL) cholesterol
concentration of plasma. Conversely, the mechanism by which statins increase high
density lipoprotein (HDL) cholesterol concentration of plasma is not well
understood. The plaque array method was used to examine the effect of statins on
in vitro cholesterol particle formation. We observed that statins induced high
density cholesterol particle formation in buffer solution with or without the
addition of human serum. Besides, simvastatin and lovastatin in their inactive
pro-drug forms modulate formation of LDL and HDL cholesterol particles,
indicating a novel nonenzymatic mechanism of statins. In a pilot study, screening
of serum samples in the assay showed variation among patient samples in response
to different statins. Specifically, screening of 50 serum samples with high
cholesterol and statin treatment, compared with standard LDL-based measurement of
statin efficacy, showed a good correlation for simvastatin (88%) and atorvastatin
(84%). Taken together, our data indicate that statins, in addition to inhibiting
enzyme-mediated cholesterol synthesis, have the capability to nonenzymatically
modulate formation of LDL and HDL cholesterol particles in vitro. Similar
interactions occurring in serum may provide a means to alter cholesterol particle
formation in vivo.
PMID- 27614851
TI - Cardiac Structural Changes and Long-Term Survival in Patients With Prominent
Thebesian Veins.
AB - Although rare, numerous case reports suggest that Thebesian veins confer
increased morbidity and mortality. No study has evaluated their effects on
cardiac structure or long-term patient outcomes. Patients undergoing coronary
angiogram at the study institution from October 2002 and January 2015 were
assessed for a diagnosis of prominent Thebesian veins. A matched control group
was created and comparisons between clinical, echocardiographic, and survival
measures were made. Of 50,116 total patients, 31 (0.06%) were found to have
prominent Thebesian veins on angiography and were compared with a matched control
group of 596 patients. Patients were matched for age, gender, angiogram date,
location and extent of coronary disease, and dominance. Demographic and clinical
data were similar between cohorts, with a median follow-up period of 26 months.
Patients with Thebesian veins had lower Doppler E wave (0.7 vs 0.8; p = 0.007)
and A wave (0.6 vs 0.8; p = 0.001) mitral inflow velocities suggesting some
decrease in normal mitral inflow, potentially due to direct shunting into the
ventricle from the Thebesian vein network. However, there was no observed
difference in left ventricular size or ejection fraction between groups. There
was also no significantly increased mortality associated with the presence of
Thebesian veins (hazard ratio 1.11, 95% CI 0.58 to 2.13). In conclusion, although
previous reports have suggested adverse outcomes from Thebesian veins, our case
control study demonstrated no significant associated adverse cardiac structural
changes or increase in mortality, although patients with Thebesian veins were
noted to have a decrease in mitral inflow velocities.
PMID- 27614852
TI - Fractional Flow Reserve-Guided Deferred Versus Complete Revascularization in
Patients With Diabetes Mellitus.
AB - To assess the safety and efficacy of deferred versus complete revascularization
using a fractional flow reserve (FFR)-guided strategy in patients with diabetes
mellitus (DM), we analyzed all DM patients who underwent FFR-guided
revascularization from January 1, 2010, to December 12, 2013. Patients were
divided into 2 groups: those with >=1 remaining FFR-negative (>0.80) medically
treated lesions [FFR(-)MT] and those with only FFR-positive lesions (<=0.80) who
underwent complete revascularization [FFR(+)CR] and were followed until July 1,
2015. The primary end point was the incidence of major adverse cardiovascular
events (MACE), a composite of death, myocardial infarction (MI), target lesion
(FFR assessed) revascularization, and rehospitalization for acute coronary
syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(-)MT and
FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 +/- 18.1
months, FFR(-)MT was associated with higher MACE rate 44.0% versus 26.6% (log
rank p = 0.02, Cox regression-adjusted hazard ratio [HR] 2.01, 95% confidence
interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end
points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for
acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target
lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI
was a strong effect modifier within the FFR(-)MT group (HR 1.98, 95% CI 1.26 to
3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95%
CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between
FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM,
particularly those with previous MI, deferred revascularization is associated
with poor medium-term outcomes. Combining FFR with imaging techniques may be
required to guide our treatment strategy in these patients with high-risk, fast
progressing atherosclerosis.
PMID- 27614853
TI - Trends in Bare-Metal Stent Use in the United States in Patients Aged >=65 Years
(from the CathPCI Registry).
AB - In 2006, the United States (US) Food and Drug Administration published advisory
highlighting concerns for late drug-eluting stent thrombosis; its impact on US
bare-metal stent (BMS) utilization is unknown. We examined rates of BMS use among
Medicare patients at 946 US hospitals in the CathPCI Registry who underwent
percutaneous coronary intervention (PCI) during 3 periods: (1) 2004 to 2006
preadvisory (n = 166,458); (2) 2007 to 2008 postadvisory (n = 216,318); and (3)
2012 to 2014 contemporary (n = 827,948). We examined predicted risks of target
vessel revascularization and bleeding among BMS recipients by period. We compared
1-year repeat revascularization and death/myocardial infarction risks among BMS
recipients immediately preadvisory and postadvisory. BMS were used in 15.8% of
preadvisory, 40.9% of postadvisory, and 20.0% of contemporary PCI procedures.
Although 19.5% of preadvisory BMS patients had a predicted target vessel
revascularization risk >=15%/year, this decreased to 16.7% postadvisory (p
<0.001), and increased back to 18.7% among contemporary BMS recipients (p
<0.001). In contrast, 12.3% of preadvisory BMS recipients had a predicted
bleeding risk >=5%/year, compared with 14.6% postadvisory (p <0.001), and 18.2%
in contemporary BMS recipients (p <0.001). Postadvisory BMS recipients had a
lower risk of repeat revascularization (12.8% vs 14.6%, adjusted hazard ratio
0.87, 95% CI 0.84 to 0.90) but no difference in the composite risk of
death/myocardial infarction (15.9% vs 15.9%, adjusted hazard ratio 0.97, 95% CI
0.93 to 1.00). In conclusion, a surge in BMS use after the advisory was not
associated with an increased risk of repeat revascularization or adverse outcomes
in BMS-treated patients. One in 5 contemporary PCI procedures still involve BMS
implantation.
PMID- 27614854
TI - Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated
Patients (from the Treating to New Targets and the Stroke Prevention by
Aggressive Reduction in Cholesterol Levels Trials).
AB - The goal of this analysis was to evaluate the ability of insulin resistance,
identified by the presence of prediabetes mellitus (PreDM) combined with either
an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI >=27.0 kg/m2),
to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM).
Consequently, a retrospective analysis of data from subjects without diabetes in
the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in
Cholesterol Levels randomized controlled trials was performed, subdividing
participants into 4 experimental groups: (1) normal fasting glucose (NFG) and TG
<=1.7 mmol/l (42%); (2) NFG and TG >1.7 mmol/l (22%); (3) PreDM and TG <=1.7
mmol/l (20%); and (4) PreDM and TG >1.7 mmol/l (15%). Comparable groupings were
created substituting BMI values (kg/m2 <27.0 and >=27.0) for TG concentrations.
Patients received atorvastatin or placebo for a median duration of 4.9 years.
Incident T2DM, defined by developing at least 2 fasting plasma glucose (FPG)
concentrations >=126 mg/dl, an increase in FPG >=37 mg/dl, or a clinical
diagnosis of T2DM, was observed in 8.2% of the total population. T2DM event rates
(statin or placebo) varied from a low of 2.8%/3.2% (NFG and TG <=1.7 mmol/l) to a
high of 22.8%/7.6% (PreDM and TG >1.7 mmol/l) with intermediate values for only
an elevated TG >1.7 mmol/l (5.2%/4.3%) or only PreDM (12.8%/7.6%). Comparable
differences were observed when BMI values were substituted for TG concentrations.
In conclusion, these data suggest that (1) the diabetogenic impact of statin
treatment is relatively modest in general; (2) the diabetogenic impact is
accentuated relatively dramatically as FPG and TG concentrations and BMI
increase; and (3) PreDM, TG concentrations, and BMI identify people at highest
risk of statin-associated T2DM.
PMID- 27614856
TI - Environmental life cycle assessment of methanol and electricity co-production
system based on coal gasification technology.
AB - This paper presents a life cycle assessment (LCA) of greenhouse gas emissions
generated through methanol and electricity co-production system based on coal
gasification technology. The analysis focuses on polygeneration technologies from
which two products are produced, and thus, issues related to an allocation
procedure for LCA are addressed in this paper. In the LCA, two methods were used:
a 'system expansion' method based on two approaches, the 'avoided burdens
approach' and 'direct system enlargement' methods and an 'allocation' method
involving proportional partitioning based on physical relationships in a
technological process. Cause-effect relationships in the analysed production
process were identified, allowing for the identification of allocation factors.
The 'system expansion' method involved expanding the analysis to include five
additional variants of electricity production technologies in Poland (alternative
technologies). This method revealed environmental consequences of implementation
for the analysed technologies. It was found that the LCA of polygeneration
technologies based on the 'system expansion' method generated a more complete
source of information on environmental consequences than the 'allocation' method.
The analysis shows that alternative technologies chosen for generating LCA
results are crucial. Life cycle assessment was performed for the analysed,
reference and variant alternative technologies. Comparative analysis was
performed between the analysed technologies of methanol and electricity co
production from coal gasification as well as a reference technology of methanol
production from the natural gas reforming process.
PMID- 27614855
TI - Usefulness of Serum B-Type Natriuretic Peptide Levels in Comatose Patients
Resuscitated from Out-of-Hospital Cardiac Arrest to Predict Outcome.
AB - N-terminal pro-B-type natriuretic (NT-proBNP) is expressed in the heart and
brain, and serum levels are elevated in acute heart and brain diseases. We aimed
to assess the possible association between serum levels and neurological outcome
and death in comatose patients resuscitated from out-of-hospital cardiac arrest
(OHCA). Of the 939 comatose OHCA patients enrolled and randomized in the Targeted
Temperature Management (TTM) trial to TTM at 33 degrees C or 36 degrees C for 24
hours, 700 were included in the biomarker substudy. Of these, 647 (92%) had serum
levels of NT-proBNP measured 24, 48, and 72 hours after return of spontaneous
circulation (ROSC). Neurological outcome was evaluated by the Cerebral
Performance Category (CPC) score and modified Rankin Scale (mRS) at 6 months. Six
hundred thirty-eight patients (99%) had serum NT-proBNP levels >=125 pg/ml.
Patients with TTM at 33 degrees C had significantly lower NT-proBNP serum levels
(median 1,472 pg/ml) than those in the 36 degrees C group (1,914 pg/ml) at 24
hours after ROSC, p <0.01 but not at 48 and 72 hours. At 24 hours, an increase in
NT-proBNP quartile was associated with death (Plogrank <0.0001). In addition, NT
proBNP serum levels > median were independently associated with poor neurological
outcome (odds ratio, ORCPC 2.02, CI 1.34 to 3.05, p <0.001; ORmRS 2.28, CI 1.50
to 3.46, p <0.001) adjusted for potential confounders. The association was
diminished at 48 and 72 hours after ROSC. In conclusion, NT-proBNP serum levels
are increased in comatose OHCA patients. Furthermore, serum NT-proBNP levels are
affected by level of TTM and are associated with death and poor neurological
outcome.
PMID- 27614857
TI - Effects of glufosinate on the growth of and microcystin production by Microcystis
aeruginosa at environmentally relevant concentrations.
AB - Harmful algal blooms (HABs) have been emerging as a worldwide issue due to their
detrimental effect to water quality and the threat to ecological health. However,
there were scarcely reports on whether existing agrochemicals such as herbicides
have potential effects on Microcystis aeruginosa (M. aeruginosa) which may form
large surface blooms. In this study, we aimed to demonstrate the effects of
glufosinate, a widely use herbicide in the world, on the growth of M. aeruginosa.
The change of the content of intracellular (intra-) and extracellular (extra-)
levels of microcystin-LR (MC-LR) were also determined by HPLC. The mRNA level of
mcyA, mcyD, mcyH related to the production of MC-LR was detected after 48h
exposure to glufosinate. Our results revealed that low concentrations of
glufosinate exposure (0.5mg/L, 1mg/L) would promote the growth of M. aeruginosa.
It was worth noting intra-MC-LR contents of algal cells were also significantly
increased at low concentrations of glufosinate exposure (1mg/L). While at high
concentrations (5mg/L, 10mg/L), glufosinate could induce the MDA level and
inhibit the growth of M. aeruginosa that would limit the production of MC-LR to
the water body. At last, the transcription levels of algae toxin synthesis
related genes mcyA and mcyD were increased significantly at environmentally
relevant concentrations of glufosinate, which may affect the MC production. This
study not only illuminated effects of glufosinate on growth of and MC-LR
synthesis of M. aeruginosa at environmentally relevant concentrations, but also
reminding us the potential risk caused by herbicide use should arouse concerns.
PMID- 27614858
TI - Temperature sensitivity of soil respiration: Synthetic effects of nitrogen and
phosphorus fertilization on Chinese Loess Plateau.
AB - Nitrogen (N) and phosphorus (P) fertilization has the potential to alter soil
respiration temperature sensitivity (Q10) by changing soil biochemical and crop
physiological process. A four-year field experiment was conducted to determine
how Q10 responded to these biochemical and physiological changes in rain-fed agro
ecosystems on the semi-arid Loess Plateau. Soil respiration, as well as biotic
and abiotic factors were measured in winter wheat (Triticum aestivum L.), with
three fertilization treatments: (no fertilization (CK), 160kgNhm-1 (N), and
160kgNha-1 with 39kgPha-1 (N+P). Mean annual soil respiration rate (calculated by
averaging the four years) in the N treatment and N+P treatment was 18% and 48%
higher than that in the CK treatment, respectively; and it was increased by 26%
(14%-48%) in the N+P treatment as compared with that in the N treatment. The
decrease of Q10 in the N and N+P treatments against the CK treatment was not
stable for each year, ranging from 0.01 to 0.28. The maximum decrease of Q10 in
the N and N+P treatments was 10% and 15% in 2014-2015, while in other years the
decrease of Q10 was numerical but not significant. Soil microbial biomass carbon
(SMBC) was increased by 10% and 50%, dissolved organic carbon (DOC) was increased
by 6% and 21%, and photosynthesis rate was increased ranging from 6% to 33% with
N and N+P fertilization. The relative abundance of Acidobacteria, Actinobacteria
and Chloroflexi were significantly higher by 32.9%-54.1% in N addition soils (N
and N+P) compared to CK treatment, whereas additional P application into soils
increased the relative abundance of the family Micrococcaceae, Nocardioidaceae
and Chitinophagaceae. Soil respiration was positively related to SMBC, DOC and
photosynthesis rate (p<0.05). However, variation in Q10 may be related to the
increase of soil mineral N content and variation of the relative abundance of
soil microbial community in our study. Nitrogen and additional phosphorus
fertilization regimes affect soil respiration and temperature sensitivity
differently.
PMID- 27614859
TI - Polycyclic aromatic hydrocarbons are associated with increased risk of chronic
obstructive pulmonary disease during haze events in China.
AB - Although exposure to particulate matter with a diameter of <2.5MUm (PM2.5) is
associated with chronic obstructive pulmonary disease (COPD), the major
components of PM2.5 in COPD pathogenesis are controversial. Here we employed the
human lung epithelial cell line BEAS-2B to elucidate the association between COPD
and the organic and water-soluble components of PM2.5. We found that the PM2.5
organic extract was a potential major risk factor for pulmonary epithelial
barrier dysfunction through the depletion of proteins from the zonula occludens.
This extract induced severe oxidative stress that increased DNA damage and the
production of proinflammatory cytokines by BEAS-2B cells as well as decreased
alpha1-antitrypsin expression, suggesting a mechanism that increases the risk of
COPD. These effects were mainly mediated by polycyclic aromatic hydrocarbons
(PAHs) through the aryl hydrocarbon receptor pathway. PAHs with high
benzo(a)pyrene (BaP)-equivalent concentrations, but not major PAH components,
have an increased risk of causing COPD, suggesting that BaP-equivalent
concentrations represent a PM2.5-induced COPD risk metric, which may contribute
to provide a rationale for the remediation of air pollution.
PMID- 27614860
TI - Adverse associations between maternal and neonatal cadmium exposure and birth
outcomes.
AB - Effects of low-level cadmium (Cd) exposure during early life on fetal growth
remain unclear. Our aim was to evaluate whether Cd exposure in maternal urine and
umbilical cord blood was associated with birth size parameters. A birth cohort
study including 1073 mother-newborn pairs was conducted from 2009 to 2010 in an
agricultural population in China. Cd concentrations were analyzed in both cord
blood and maternal urine. Generalized linear models were performed to determine
associations between maternal and neonatal exposure to Cd and birth indicators,
including birth weight, length, head circumference and ponderal index. The median
(25th to 75th percentile) value of Cd concentration in maternal urine and
umbilical cord blood was 0.19 (0.08, 1.00) MUg/L and 0.40 (0.05). CO2 emissions significantly increased in microalgal biofilm
treatment (p<0.01), which was also responsible for the highest N2O emissions
(p<0.01). The ammonia (NNH3) volatilization losses were 4.63%, 18.98%, and 0.82%
for the microalgal biofilm, urea, and control treatments, respectively. The main
differences in soil characteristics were an increase in nitrogen and an increase
in cation exchange capacity (p<0.01) caused by the algal biomass application to
the soil. The soil organic matter content significantly differed (p<0.05) among
the three treatments, with the microalgal biofilm treatment having the greatest
increase in soil organic matter. Significant differences were observed for shoot
dry matter mass and nitrogen content in the plants from both treatments where
nitrogen sources were applied. All treatments differed from each other in leaf
dry matter mass, with the urea treatment increasing the most. Chlorella vulgaris
was the dominant microalgal specie in the soil.
PMID- 27614862
TI - Soil-to-plant transfer of arsenic and phosphorus along a contamination gradient
in the mining-impacted Ogosta River floodplain.
AB - Riverine floodplains downstream of active or former metal sulfide mines are in
many cases contaminated with trace metals and metalloids, including arsenic (As).
Since decontamination of such floodplains on a large scale is unfeasible,
management of contaminated land must focus on providing land use guidelines or
even restrictions. This should be based on knowledge about how contaminants enter
the food chain. For As, uptake by plants may be an important pathway, but the As
soil-to-plant transfer under field conditions is poorly understood. Here, we
investigated the soil-to-shoot transfer of As and phosphorus (P) in wild
populations of herbaceous species growing along an As contamination gradient
across an extensive pasture in the mining-impacted Ogosta River floodplain. The
As concentrations in the shoots of Trifolium repens and Holcus lanatus reflected
the soil contamination gradient. However, the soil-to-shoot transfer factors (TF)
were fairly low, with values mostly below 0.07 (TF=Asshoot/Assoil). We found no
evidence for interference of As with P uptake by plants, despite extremely high
molar As:P ratios (up to 2.6) in Olsen soil extracts of the most contaminated
topsoils (0-20cm). Considering the restricted soil-to-shoot transfer, we
estimated that for grazing livestock As intake via soil ingestion is likely more
important than intake via pasture herbage.
PMID- 27614863
TI - Exposure to pesticides and the associated human health effects.
AB - Pesticides are used widely to control weeds and insect infestation in
agricultural fields and various pests and disease carriers (e.g., mosquitoes,
ticks, rats, and mice) in houses, offices, malls, and streets. As the modes of
action for pesticides are not species-specific, concerns have been raised about
environmental risks associated with their exposure through various routes (e.g.,
residues in food and drinking water). Although such hazards range from short-term
(e.g., skin and eye irritation, headaches, dizziness, and nausea) to chronic
impacts (e.g., cancer, asthma, and diabetes), their risks are difficult to
elucidate due to the involvement of various factors (e.g., period and level of
exposure, type of pesticide (regarding toxicity and persistence), and the
environmental characteristics of the affected areas). There are no groups in the
human population that are completely unexposed to pesticides while most diseases
are multi-causal to add considerable complexity to public health assessments.
Hence, development of eco-friendly pesticide alternatives (e.g., EcoSMART) and
Integrated Pest Management (IPM) techniques is desirable to reduce the impacts of
pesticides. This paper was hence organized to present a comprehensive review on
pesticides with respect to their types, environmental distribution, routes of
exposure, and health impacts.
PMID- 27614864
TI - Statistical associations between housing quality and health among Finnish
households with children - Results from two (repeated) national surveys.
AB - The overall aim of the study was to assess housing and health issues related to
Finnish housing stock and possible changes occurring in the course of time. Based
on two housing and health questionnaire surveys, first one in 2007 and the second
one in 2011, we examined factors associated with housing satisfaction and health
symptoms that residents themselves reported on a general population level. A
special emphasis was on housing quality and health issues among households with
children. The total number of survey responses was 2674, response rate being
slightly lower in the 2011 (29%) survey than in 2007 (43%). Differences in
housing and health issues observed between 2007 and 2011 surveys were relatively
small. From the various housing factors studied, largest differences between
surveys were seen in thermal comfort during summer, which could be attributed to
climate factors. From the five health outcome variables studied, only self
reported upper respiratory symptoms appeared to have significant temporal
variation between the surveys. Overall, issues related to crowding,
inaccessibility, use of chemicals, indoor air quality (e.g. ventilation
adequacy), and dampness and mold could cause more unsatisfactory housing
conditions among the families with children. Respondents who had children
reported respiratory symptoms less commonly, whereas risk for respiratory
infections was increased among these respondents. Modeling self-reported health
symptoms led to selection of nine to twelve statistically significant housing
variables together with up to five socio-economic variables, i.e. complex models
which are difficult to interpret quantitatively. The models' sensitivity for
properly indicating symptoms was rather low, varying from 4% to 22%, which
illustrates that it is quite impossible to predict individuals' symptoms with a
set of housing characteristics. However, the associations observed on the
population level may be used to develop policies that are protective of public
health.
PMID- 27614865
TI - Interaction between diabetes mellitus and hypertension on risk of hearing loss in
highly endogamous population.
AB - AIM: The aim of this study was to determine the prevalence of hearing loss and
its association with type 2 diabetes mellitus (T2DM) in a highly endogamous
population. DESIGN: This is a cross-sectional study. SETTING: The present study
is carried out in Ear Nose Throat (ENT) and Endocrinology outpatient clinics of
the Hamad General and Rumeilah Hospitals, Hamad Medical Corporation. SUBJECTS:
All subjects aged between 20 and 59 years who visited the Endocrinology and ENT
outpatient clinics of the Hamad Medical Corporation with hearing difficulty were
included in this study during the period from January 2013 to July 2014. METHOD:
During the study period, prevalence, hearing, audiological test, family history
and medical problems associated with hearing impairment in middle aged patients
were recorded. Two audiometers Grason Stadler GSI 61 and Madsen Orbiter 922 were
used to evaluate the hearing loss. RESULT: Majority of the hearing loss observed
at the age above 45 years old, (44.8% vs 51.7%, p=0.05). The prevalence of
hearing impairment was higher in Qataris than in non-Qataris (59.7% vs 46.6%,
p<0.001). The consanguineous marriages were observed higher in Hearing loss
(32.1%) than in normal hearing (21.8%) (p=0.028). The mean of diabetes onset
duration (7.8+/-4.12years), sleeping disorder (5.81+/-1.29h), obese subjects (38%
vs 27.4%); family history of diabetes (30.6 vs 23.1%) were higher among hearing
impairment. The associated risk factors were significantly higher in T2DM with
hearing loss, hypoglycemia (32.8% vs 27.4%), retinopathy (313% vs 18.5%),
Nephropathy (17.9% vs 9.8%), Neuropathy (17.9% vs 10.2%), macro-vascular disease
(11.9% vs 6.2%), diabetic foot ulcer (20.9% vs 12.6%), Tinnitus (68.7% vs 51.3%),
and Vertigo (25.4% vs 16.9%) than in normal hearing diabetes. There was a
statistically significant differences between hearing impairment and normal
hearing among T2DM regarding hearing assessment frequency (p=0.041). There were
statistically significant differences between hearing impairment versus normal
hearing for vitamin D [18.91+/-7.65ng/mL vs 22.85+/-9.00ng/mL; p<0.001], calcium
[1.80+/-0.12ng/mL vs 1.96+/-0.14mmol/L; p<0.001], magnesium [0.80+/-0.09mmol/L vs
0.8+/-0.14mmol/L; p<0.001], phosphorous [1.42+/-0.30mmol/L vs 1.56+/-0.26mmol/L;
p<0.001], ceatinine [1.42+/-0.30mmol/L vs 1.56+/-0.26mmol/L; p<0.001],
cholesterol [4.92+/-1.08mmol/L vs 4.40+/-1.01mmol/L; p=0.035], LDL [1.92+/
0.88mmol/L vs 2.09+/-0.92mmol/L; p=0.024], albumin [43.1+/-6.10mmol/L vs 39.8+/
7.93mmol/L; p=0.010], systolic blood pressure [135.8+/-16.6Hg vs 130.2+/-12.5Hg;
p=0.017] and, diastolic blood pressure [85.1+/-9.2mmHg vs 83.0+/-7.9mmHg;
p=0.012]. There were highly statistically significant differences between hearing
impairment versus normal for both side right and left ear frequency in Db unit
(p<0.001). The multivariate stepwise logistic regression analysis revealed that
head ache (p<0.001), family history of DM (p<0.001), sleep disturbance (p<0.001),
high blood pressure (p=0.006), consanguinity (p=0.010), nationality (p=0.014),
age in years (p=0.025), and sheesha smokers (p=0.045) were considered at higher
risk as a predictors of hearing loss among diabetic patients. CONCLUSION: The
current study results confirm previous reports that adults with DM and
hypertension associated showed greater hearing impairment in highly endogamous
population... Diabetic patients with hearing loss were likely to have high blood
glucose and other risk factors like hypertension, retinopathy, nephropathy and
neuropathy.
PMID- 27614866
TI - Assessment of insulin injection techniques among diabetes patients in a tertiary
care centre.
AB - AIMS: The efficacy of insulin therapy in diabetes depends on proper storage and
injection technique. The purpose of this study was to assess the practice of
insulin administration among diabetes patients in a tertiary care center.
MATERIALS AND METHODS: This observational study was done in Endocrinology
department of a tertiary care center during April-June 2015. The consecutive
patients using insulin for at least three months by either syringe or pen were
recruited. All of them underwent a survey by the questionnaire which focused on
key insulin injection parameters. RESULTS: One hundred and sixty eight (74.67%)
patients were storing insulin vials properly. The thigh was the most common site
of insulin injection and 209(92.89%) study participants were rotating at the
injection sites. Only 48.57% (34/70) subjects were mixing insulin properly before
injection. The practice of hand washing and the cleaning of the injection site
was practiced by 158(70%) & 171(76.44%) subjects respectively. One hundred and
fifty six (69%) patients were injecting with the proper skin fold and 123(55%)
subjects were injecting insulin at 90 degrees angle. The majority of patients
(91%) were throwing the needle and syringes directly into the garbage and public
drainage system. CONCLUSIONS: There was a significant gap between the insulin
administration guidelines and current insulin injection practice. The diabetic
education and counseling about proper insulin injection techniques should be
provided to all diabetic subjects.
PMID- 27614867
TI - Infusion reactions are common after high-dose carmustine in BEAM chemotherapy and
are not reduced by lengthening the time of administration.
AB - PURPOSE: Carmustine (BCNU) is used in the conditioning regimens BEAM and CBV for
autologous stem cell transplantation. Carmustine-related infusion reactions,
while not described in the BEAM literature, occurred in 95 % of patients who
received CBV. The most common symptoms include flushing, facial pain, headache,
and hypotension. These reactions have been attributed to the absolute ethanol
that is used in the reconstitution process or alternatively by a direct effect of
carmustine. It is currently recommended that carmustine 300 mg/m2 be infused over
at least 100 min (3-5 mg/m2/min). Prior to October 2014, carmustine infusions
were given over 90 min but were changed to 120 min based on the above
recommendation. We compared the two infusion rates in patients receiving BEAM to
see if lengthening the infusion decreased the frequency of reactions. METHODS:
Overall, 100 patients received BCNU as part of BEAM or Zevalin BEAM and were
equally divided between 90 and 120 min infusion times. The primary outcome was
the incidence of infusion-related reactions which were graded based on CTCAE 4.03
descriptions of flushing and infusion-related reactions. We also evaluated the
impact of premedication as well as the efficacy of medications used to treat
infusion reactions. RESULTS: Between the years 2013-2016, there were 50 patients
who received BCNU over 90 min and 50 patients over 120 min. There were no
significant differences observed for diagnosis, age and gender between the two
groups. Twenty-eight (56 %) in the 90-min and 26 (52 %) in the 120-min infusion
intervals developed a reaction (p = 0.6882). Of the patients that developed a
reaction, 19 patients (67 %) in the 90-min and all 26 patients (100 %) in the 120
min infusion were given premedications predominately acetaminophen, in addition
to dexamethasone. Among reacting patients, 57 % of the 90-min and 65 % of the 120
min groups received additional intervention (p = 0.53). CONCLUSION: Infusion
reactions during high-dose BCNU are common and are not clearly reduced by
modestly extending the duration of infusion or giving premedications.
PMID- 27614868
TI - Impact of a supportive care service for cancer outpatients: management and
reduction of hospitalizations. Preliminary results of an integrated model of
care.
AB - PURPOSE: Supportive care in oncology is a primary need for every oncology
department nowadays. In 2012, in our institution, a dedicated supportive care
service (SCS) was created in order to deal with any need our on-treatment
patients might have (e.g. tumour-related or treatment-related symptoms). We
hypothesized that this service had a positive impact on the number of unplanned
hospitalizations; to confirm our hypothesis, we decided to review admission data
in 2011 and 2012. METHODS: Using our internal software, we compared admission
data in 2011 (that is, the year before the dedicated service was created) and
2012 (when such service began, that is April of that year). We also made an
evaluation of the costs of these hospitalizations. RESULTS: Despite an increase
of the number of patients treated in our day hospital (+6.5 %), the number of
unplanned hospital admissions decreased by 3.2 % (from 17.3 to 14.1 %). The
number of patients accessing to emergency room went from 66 to 61 % (a reduction
of 5 %). The costs of these hospitalizations were reduced by 2.2 %. CONCLUSIONS:
The introduction of the dedicated SCS in our oncology department caused a net
reduction by 3.2 % of the number of unplanned hospitalizations of on-treatment
cancer patients.
PMID- 27614869
TI - Patient- and family-centered care: a qualitative exploration of oncologist
perspectives.
AB - PURPOSE: Increasingly, patient- and family-centered care (PFCC) is recognized as
a valuable component of healthcare reform with rich opportunities for improvement
within oncology. Shifting toward PFCC requires physician buy-in; however,
research examining their perspectives on PFCC is lacking. We sought to explore
oncologists' perspectives on PFCC to identify factors that influence their
ability to practice PFCC. METHODS: We conducted semi-structured interviews with
18 oncologists (8 radiation, 4 medical, 4 surgical, 2 hematologist-oncologists)
at a single Canadian academic cancer institution. Interview data were analyzed
using thematic analysis and principles drawn from grounded theory. Subsequently,
focus groups consisting of the interviewed participants were facilitated to
confirm and elaborate on our findings. Constant comparisons were used to identify
recurring themes. RESULTS: Three dominant themes emerged. First, physicians
displayed cautious engagement in their approach to PFCC. Collectively,
participants understood the general principles of PFCC. However, there was a
limited understanding of the value, implications, and motivation for improving
PFCC which may create reluctance with physician buy-in. Second, both individual
and system barriers to practicing PFCC were identified. A lack of physician
acknowledgement and engagement and competing responsibilities emerged as provider
level challenges. System barriers included impaired clinic workflow, physical
infrastructure constraints, and delays in access to care. Third, physicians were
able to identify existing and potential PFCC behaviors that were feasible within
existing system constraints. CONCLUSIONS: Advancing PFCC will require continued
physician education regarding the value of PFCC, acknowledgement and preservation
of effective patient- and family-centered strategies, and creative solutions to
address the system constraints to delivering PFCC.
PMID- 27614870
TI - Critical review of current clinical practice guidelines for antifungal therapy in
paediatric haematology and oncology.
AB - PURPOSE: The incidence of invasive fungal disease (IFD) is rising, but its
treatment in paediatric haematology and oncology patients is not yet
standardised. This review aimed to critically appraise and analyse the clinical
practice guidelines (CPGs) that are available for paediatric IFD. METHODS:
Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations,
the Guidelines International Network (GIN), guideline.gov and Google were
performed and combined fungal disease (Fung* OR antifung*OR Candida* OR
Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All
guidelines were assessed using the AGREE II tool and recommendations relating to
prophylaxis, empirical treatment and specific therapy were extracted. RESULTS:
Nineteen guidelines met the inclusion criteria. The AGREE II scores for the
rigour of development domain ranged from 11 to 92 % with a median of 53 %
(interquartile range 32-69 %). Fluconazole was recommended as antifungal
prophylaxis in all nine of the included guidelines which recommended a specific
drug. Liposomal amphotericin B was recommended in all five guidelines giving
empirical therapy recommendations. Specific therapy recommendations were given
for oral or genital candidiasis, invasive candida infection, invasive
aspergillosis and other mould infections. CONCLUSIONS: In many areas,
recommendations were clear about appropriate practice but further clarity was
required, particularly relating to the decision to discontinue empirical
antifungal treatment, the relative benefits of empiric and pre-emptive strategies
and risk stratification. Future CPGs could consider working to published
guideline production methodologies and sharing summaries of evidence appraisal to
reduce duplication of effort, improving the quality and efficiency of CPGs in
this area.
PMID- 27614871
TI - Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial
Fibrosis via Nrf2-Mediated Inhibition of TGF-beta1/Smad3 Pathway in Myocardial
Infarction Mice.
AB - AIMS: Myocardial interstitial fibrosis is a major histologic landmark resulting
in cardiac dysfunction after myocardial infarction (MI). Activation of
cannabinoid receptor type II (CB2 receptor) have been demonstrated to reduce
fibrosis in hepatic cirrhotic rat. However, the anti-fibrotic effect of CB2
receptor activation in infarcted hearts was still unclear. In this study, we
aimed to investigate the effects of a CB2 receptor selective agonist AM1241 on
myocardial fibrosis post MI in mice. METHODS: Echocardiograph was conducted to
assess cardiac function. Fibrosis markers such as type I and type III collagen,
fibronectin, Plasminogen activator inhibitor(PAI)-1 and tissue inhibitor of
metalloprotease(TIMP)-1 were examined by Western blot, while collagens were
directly observed by Sirius-red staining. Primary cultured cardiac
fibroblasts(CFs) were subjected to hypoxia/serum deprivation (H/SD) injury to
simulate ischemic conditions in vivo. Nrf2 siRNA were applied to explore the role
of Nrf2 and TGF-beta1/Smad3 pathway in this process. RESULTS: Echocardiography
showed that AM1241 significantly improved cardiac function, suppressed the
expression of fibrosis markers such as collagen I and collagen III, fibronectin,
PAI-1 and TIMP-1 in mice with MI. In cardiac fibroblasts subjected to H/SD
injury, AM1241 reduced the elevated levels of alpha-SMA, collagen I and collagen
III, which were partially abrogated by the Nrf2 siRNA transfection. Furthermore,
AM1241 not only activated and accelerated the translocation of Nrf2 to nucleus,
but also inhibited TGF-beta1/ Smad3 pathway in an Nrf2 dependent manner.
CONCLUSION: CB2 receptor agonist AM1241 alleviated myocardial interstitial
fibrosis via Nrf2 -mediated down-regulation of TGF-beta1/Smad3 pathway, which
suggested that CB2 receptor activation might represent a promising target for
retarding cardiac fibrosis after MI.
PMID- 27614872
TI - Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with
Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup
Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE).
AB - BACKGROUND: In the SQUIRE study, adding the anti-epidermal growth factor receptor
(EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N)
in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved
overall survival (OS); the safety profile was acceptable. We explored data for
the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors.
PATIENT AND METHODS: Patients with stage IV sqNSCLC were randomized 1:1 to up to
6 cycles of open-label GC + N or GC alone. GC + N patients with no progression
continued on necitumumab monotherapy until disease progression or intolerable
toxicity. The primary endpoint was OS; the secondary endpoints included
progression-free survival (PFS), safety and health-related quality of life (EQ
5D, Lung Cancer Symptom Scale (LCSS)). RESULTS: The 96 German SQUIRE patients
with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles;
the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was
associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95%
confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of
progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically
associated with EGFR antibody treatment (including rash, hypomagnesemia) were
more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores
showed no notable differences between the treatment arms, except for appetite
loss (delayed for GC + N). CONCLUSION: The survival benefit from adding
necitumumab to first-line GC was more pronounced in the German SQUIRE
subpopulation with EGFR-expressing tumors than in the overall (intention-to
treat) population; toxicity was manageable and consistent with the overall
population.
PMID- 27614873
TI - Prevalence of Sickle Cell Trait and Reliability of Self-Reported Status among
Expectant Parents in Nigeria: Implications for Targeted Newborn Screening.
AB - BACKGROUND/AIMS: Sickle cell disease (SCD) is a life-threatening, autosomal
recessive blood disorder prevalent in sub-Saharan Africa. We identified the
prevalence of sickle cell trait (SCT) among pregnant women and their male
partners in Enugu State, Nigeria, and determined the accuracy of self-reported
sickle cell status and its reliability for identifying high-risk newborns for
targeted screening. METHODS: We conducted a nested cohort study of expectant
parents enrolled in the Healthy Beginning Initiative (HBI). The HBI is a cluster
randomized trial of a congregation-based approach designed to increase HIV
testing. Participants completed a survey regarding self-awareness of their sickle
cell genotype and consented to genotype screening by cellulose acetate
electrophoresis. RESULTS: SCT prevalence (HbAS) was 22% (746/3,371). Only 50% of
participants provided an accurate self-report. Self-report accuracy was
significantly different (p < 0.0001) between individuals who reported having SCT
or SCD (61% accuracy) versus those who reported not having SCT or SCD (86%
accuracy). Demographic variables including gender, age, household size,
employment, education, and home location were significantly associated with
providing an accurate self-report. CONCLUSIONS: Low numbers of accurate parental
self-reports, coupled with a high SCT prevalence in Nigeria, could limit the
efficacy of targeted newborn screening. However, our data indicate that it is
feasible to integrate sickle cell screening for pregnant women with existing,
community-based health care programs developed by the President's Emergency Plan
for AIDS Relief (PEPFAR), such as the HBI. Expanding screening programs could
enable the development of targeted newborn screening based on maternal genotype
that could identify all newborns with SCD in resource-limited settings.
PMID- 27614874
TI - Clinical Impact of 123I-Ioflupane SPECT (DaTscan) in a Movement Disorder Center.
AB - BACKGROUND/AIMS: The clinical diagnosis of degenerative forms of parkinsonism is
imperfect, with past studies reporting a high rate of misdiagnosis by
neurologists and movement disorder specialists, particularly early in the disease
course. 123I-ioflupane SPECT (DaTscan) is a diagnostic neuroimaging tool used to
distinguish essential tremor from tremor due to degenerative parkinsonisms. The
present study expands upon prior studies of the clinical impact of DaTscan
imaging in movement disorder centers by assessing quantitative estimates of
diagnostic certainty, the impact on subsequent clinical decisions, and the degree
to which the asymmetry in the results corresponds to laterality by clinical
history and examination. METHODS: In a prospective, observational study of the
impact of DaTscan imaging in a movement disorder center over the course of 18
months, 4 specialists completed a questionnaire at the time they ordered imaging
and again within 1 month after imaging. RESULTS: Twenty-seven patients underwent
DaTscan imaging; the result was normal in 4 cases (14.8%), abnormal in 22 cases
(81.4%), and equivocal in 1 case (3.7%). In all cases of a normal result, the
post-scan-predicted chance of degenerative parkinsonism decreased compared to the
pre-scan prediction (p < 0.05), and in all cases of abnormal scan, the post-scan
chance of degenerative parkinsonism increased or remained high (p < 0.0001).
Clinical impacts were observed following imaging in a total of 24 patients
(88.9%), including changes in medications for 18 patients and psychological
impacts for 11 patients. Asymmetric clinical symptoms were corroborated based on
the expected asymmetry of dopamine uptake deficits in 57.1% of the cases, were
not present in 23.8%, and were opposite of expectations in 19.0% of the scans.
CONCLUSION: DaTscan imaging results have an impact on physician's confidence in
the diagnosis of parkinsonism and may also have a psychological impact on
patients. DaTscan imaging may be a useful adjunct to clinical history and
examination in selected patients.
PMID- 27614875
TI - Surgical Treatment of Early-Stage Cervical Cancer.
AB - Surgical treatment of cervical cancer has been a cornerstone in the management of
this malignancy for more than 100 years. Today, for early-stage and low-risk
cervical cancer, surgery is still considered the gold standard. If the
preoperative assessment of the tumor reveals a situation prompting postoperative
adjuvant radiochemotherapy, the latter should be planned as the primary treatment
option, being preceded by staging laparoscopy including pelvic and paraaortic
lymph node dissection. As an alternative to the open approach, the definitive
surgical treatment should be either performed laparoscopically, or be
laparoscopic-assisted, or laparoscopically robotic-assisted.
PMID- 27614876
TI - PM2.5 pollution from household solid fuel burning practices in central India: 1.
Impact on indoor air quality and associated health risks.
AB - PM2.5 concentrations were measured in residential indoor environment in slums of
central India during 2012-2013. In addition, a suite of chemical components
including metals (Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, Pb, Mo, Se,
Sb, Na, Mg, K and Hg), ions (Na+, Mg2+, K+, Ca2+, F-, Cl-, NH4+, NO3- and SO42-)
and carbon (OC and EC) were analyzed for all samples. Indoor PM2.5 concentrations
were found to be several folds higher than the 24-h national ambient air quality
standard (60 ug/m3) for PM2.5 in India, and the concentrations were found to vary
from season to season. Mass closure was attempted for PM2.5 data, and close to
100 % mass was accounted for by organic matter, crustal material, secondary
organic and inorganic aerosols and elemental carbon. Additionally, carcinogenic
and non-carcinogenic health risks associated with exposure to indoor PM2.5
(inhalation, dermal and ingestion) were estimated and while exposures associated
with dermal contact and ingestion were found to be within the acceptable limits,
risk associated with inhalation exposure was found to be high for children and
adults. Elements including Al, Cd, Co, Cr, Mn, Ni, As and Pb were present in high
concentrations and contributed to carcinogenic and non-carcinogenic risks for
residents' health. Results from this study highlight the need for efforts to
reduce air pollution exposure in slum areas.
PMID- 27614877
TI - Disclosure of HIV Status Beyond Sexual Partners by People Living with HIV in
France: A Call for Help? Results from the National Cross-Sectional Survey ANRS
VESPA2.
AB - HIV status disclosure remains a complex issue for most people living with HIV
(PLWH). We analyzed PLWH disclosure behaviors in France, where treatment is free
and where the social image of HIV has improved in the general population.
Analyses focused on disclosure to the social network excluding sexual partners
(close family, other relatives, friends, colleagues). The study sample comprised
3016 participants from the nationally representative survey ANRS-VESPA2. Three
PLWH clusters were identified using hierarchical classification ("high disclosure
level": 28.2 %, "medium disclosure level": 27.5 %, and "low disclosure level":
44.3 %). In multivariable analyses, the variable "not living in a couple but
psychological social support needed" was independently associated with medium
(AOR [95 % CI] 1.8 [1.4; 2.3]) and high levels of disclosure (1.4 [1.1; 1.8])
(multinomial regression models). For PLWH living alone, HIV status disclosure may
reveal a need for psychological social support, a key component to treatment
adherence and positive prevention.
PMID- 27614879
TI - A comprehensive study of oxidative stress in sudden hearing loss.
AB - Little is known about the association between idiopathic sudden sensorineural
hearing loss (ISSNHL) and oxidative stress. We investigated changes in a wide
range of oxidants and antioxidants to create a comprehensive picture of oxidative
imbalance. In the peripheral blood of 50 ISSNHL patients and 50 healthy subjects,
total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON),
thiol/disulphide levels were measured. Moreover, a global oxidative stress index,
reflecting both oxidative and antioxidant counterparts, was also calculated. One
way analysis between oxidative markers and severity of hearing loss were
evaluated. The ISSNHL patients showed significantly higher TOS levels than
controls (6.02 +/- 3.17 vs. 4.5 +/- 2.22; p = 0.018). The oxidative index was
also significantly higher in patients than controls (0.39 +/- 0.19 vs. 0.3 +/-
0.14; p = 0.035). TAS, PON, native thiol, and total thiol were not altered. There
was no statistical significance between oxidative markers and severity of hearing
loss. The binary logistic regression model revealed that disulphide and TOS were
associated with ISSNHL. There are alterations in a wide array of oxidants and
antioxidants, with balance shifting toward increased oxidative stress in ISSNHL.
Our findings may suggest endothelial dysfunction in ISSNHL etiopathogenesis.
PMID- 27614878
TI - SIRT1 Overexpression in Mouse Hippocampus Induces Cognitive Enhancement Through
Proteostatic and Neurotrophic Mechanisms.
AB - SIRT1 induces cell survival and has shown neuroprotection against amyloid and tau
pathologies in Alzheimer's disease (AD). However, protective effects against
memory loss or the enhancement of cognitive functions have not yet been proven.
We aimed to investigate the benefits induced by SIRT1 overexpression in the
hippocampus of the AD mouse model 3xTg-AD and in control non-transgenic mice. A
lentiviral vector encoding mouse SIRT1 or GFP, selectively transducing neurons,
was injected into the dorsal CA1 hippocampal area of 4-month-old mice. Six-month
overexpression of SIRT1 fully preserved learning and memory in 10-month-old 3xTg
AD mice. Remarkably, SIRT1 also induced cognitive enhancement in healthy non
transgenic mice. Neuron cultures of 3xTg-AD mice, which show traits of AD-like
pathology, and neuron cultures from non-transgenic mice were also transduced with
lentiviral vectors to analyze beneficial SIRT1 mechanisms. We uncovered novel
pathways of SIRT1 neuroprotection through enhancement of cell proteostatic
mechanisms and activation of neurotrophic factors not previously reported such as
GDNF, present in both AD-like and healthy neurons. Therefore, SIRT1 may increase
neuron function and resilience against AD.
PMID- 27614880
TI - The effect of exercise hypertrophy and disuse atrophy on muscle contractile
properties: a mechanomyographic analysis.
AB - PURPOSE: To determine whether mechanomyographic (MMG) determined contractile
properties of the biceps brachii change during exercise-induced hypertrophy and
subsequent disuse atrophy. METHODS: Healthy subjects (mean +/- SD, 23.7 +/- 2.6
years, BMI 21.8 +/- 2.4, n = 19) performed unilateral biceps curls (9 sets * 12
repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing
exercise (atrophic phase) for the following 8 weeks (non-dominant limb;
treatment, dominant limb; control). MMG measures of muscle contractile properties
(contraction time; T c, maximum displacement; D max, contraction velocity; V c),
electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF),
strength measures (maximum voluntary contraction; MVC) and measures of muscle
thickness (ultrasound) were obtained. RESULTS: Two-way repeated measures ANOVA
showed significant differences (P < 0.05) between treatment and control limbs.
During the hypertrophic phase treatment MVC initially declined (weeks 1-3), due
to fatigue (decline in MPF), followed by improvement against control during weeks
6-8. Between weeks 5 and 8 treatment, muscle thickness was greater than control,
reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8)
declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks
9, 10) initially remained high before declining to control levels, reflecting
gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also
declined during the atrophic phase. No change in T c was found throughout the
hypertrophic or atrophic phases. CONCLUSIONS: MMG detects changes in contractile
properties during stages of exercise-induced hypertrophy and disuse atrophy
suggesting its applicability as a clinical tool in musculoskeletal
rehabilitation.
PMID- 27614881
TI - Heritability of heart rate recovery and vagal rebound after exercise.
AB - PURPOSE: The prognostic power of heart rate recovery (HRR) after exercise has
been well established but the exact origin of individual differences in HRR
remains unclear. This study aims to estimate the heritability of HRR and vagal
rebound after maximal exercise in adolescents. Furthermore, the role of voluntary
regular exercise behavior (EB) in HRR and vagal rebound is tested. METHODS: 491
healthy adolescent twins and their siblings were recruited for maximal exercise
testing, followed by a standardized cooldown with measurement of the
electrocardiogram and respiratory frequency. Immediate and long-term HRR (HRR60
and HRR180) and vagal rebound (heart rate variability in the respiratory
frequency range) were assessed 1 and 3 min after exercise. Multivariate twin
modeling was used to estimate heritability of all measured variables and to
compute the genetic contribution to their covariance. RESULTS: Heritability of
HRR60, HRR180 and immediate and long-term vagal rebound is 60 % (95 % CI: 48-67),
65 % (95 % CI: 54-73), 23 % (95 % CI: 11-35) and 3 % (95 % CI: 0-11),
respectively. We find evidence for two separate genetic factors with one factor
influencing overall cardiac vagal control, including resting heart rate and
respiratory sinus arrhythmia, and a specific factor for cardiac vagal exercise
recovery. EB was only modestly associated with resting heart rate (r = -0.27) and
HRR (rHRR60 = 0.10; rHRR180 = 0.19) with very high genetic contribution to these
associations (88-91 %). CONCLUSIONS: Individual differences in HRR and immediate
vagal rebound can to a large extent be explained by genetic factors. These innate
cardiac vagal exercise recovery factors partly reflect the effects of heritable
differences in EB.
PMID- 27614883
TI - Cardiac stroke volume variability measured non-invasively by three methods for
detection of central hypovolemia in healthy humans.
AB - PURPOSE: Hypovolemia decreases preload and cardiac stroke volume. Cardiac stroke
volume (SV) and its variability (cardiac stroke volume variability, SVV) have
been proposed as clinical tools for detection of acute hemorrhage. We compared
three non-invasive SV measurements and investigated if respiration-induced
fluctuations in SV may detect mild and moderate hypovolemia in spontaneously
breathing humans. METHODS: Ten healthy subjects underwent experimental central
hypovolemia induced by lower body negative pressure to -60 mmHg or onset of
presyncopal symptoms. SV beat-to-beat was estimated simultaneously by ultrasound
Doppler, finger arterial blood pressure curve and impedance cardiography. SVV was
calculated by spectral analysis between 0.15 and 0.40 Hz. RESULTS: Relative
changes in SV did not show significant differences between the methods. The SVV
measured by ultrasound Doppler and arterial blood pressure curve decreased at -30
mmHg to 32 % (ultrasound Doppler: 95 % CI 18-47, arterial blood pressure curve:
95 % CI 21-43) and at maximal simulated hypovolemia to 23 % (ultrasound Doppler:
95 % CI 14-81) and 21 % (arterial blood pressure curve: 95 % CI 9-33) of baseline
variability. The variability in cardiac stroke volume from the impedance
cardiography did not change significantly during the simulated hypovolemia, to 88
and 76 % of baseline variability. CONCLUSION: Cardiac stroke volume estimated by
ultrasound Doppler and by arterial blood pressure curve showed parallel
variations beat-to-beat during simulated hemorrhage, whereas impedance
cardiography did not appear to track beat-to-beat changes in cardiac stroke
volume. The variability in cardiac stroke volume was decreased during mild and
moderate hypovolemia and could be used for early detection of hypovolemia.
PMID- 27614884
TI - Automatic tube current modulation for whole-body polytrauma CT with
immobilization devices: is there an increase in radiation dose and degradation of
image quality?
AB - The objective of this study was the assessment of the image quality and radiation
dose in polytrauma CT using immobilization devices. An anthropomorphic whole body
and a liver phantom were scanned on a 128-slice CT scanner with four different
protocols using automatic tube current modulation (120 kVp, 150 ref. mAs; 120 kV,
200 ref. mAs; 140 kVp, 150 ref. mAs; and 140 kVp, 200 ref. mAs) and four
different setups (no immobilization device (setup A), vacuum mattress 1 (setup
B), vacuum mattress 2 (setup C), and spineboard (setup D)). Qualitative and
quantitative image quality parameters and radiation dose were assessed. Image
noise increased on average by 6.6, 11.2, and 9.4 %, and CNR decreased by 11.2,
13.9, and 6.5 for setups B, C, and D, respectively, compared with setup A. The
CTDIvol increased up to 6 % using immobilization devices. Severe streak
artifacts, provoked by the inflation valve of the mattresses were detected at the
level of the head and shoulder. Applying immobilization devices for whole-body CT
with automatic tube current modulation increases the radiation dose and decreases
the quantitative image quality slightly. Severe artifacts, induced by the
inflation valve of the mattress, can influence the diagnostic accuracy at the
level of the head and shoulder.
PMID- 27614882
TI - Markers of biological stress in response to a single session of high-intensity
interval training and high-volume training in young athletes.
AB - PURPOSE: The aim of the present study was to compare the effects of high
intensity interval training (HIIT) vs high-volume training (HVT) on salivary
stress markers [cortisol (sC), testosterone (sT), alpha-amylase (sAA)], metabolic
and cardiorespiratory response in young athletes. METHODS: Twelve young male
cyclists (14 +/- 1 years; 57.9 +/- 9.4 mL min-1 kg-1 peak oxygen uptake)
performed one session of HIIT (4 * 4 min intervals at 90-95 % peak power output
separated by 3 min of active rest) and one session of HVT (90 min constant load
at 60 % peak power output). The levels of sC, sT, their ratio (sT/sC) and sAA
were determined before and 0, 30, 60, 180 min after each intervention. Metabolic
and cardiorespiratory stress was characterized by blood lactate, blood pH,
respiratory exchange ratio (RER) and heart rate (HR), oxygen uptake ([Formula:
see text]), ventilation (V E) and ventilatory equivalent (V E/[Formula: see
text]). RESULTS: sC increased 30 and 60 min after HIIT. However, 180 min post
exercise, sC decreased below baseline levels in both conditions. sT increased 0
and 30 min after HIIT and 0 min after HVT. sAA and sT/sC ratio did not change
significantly over time in HIIT nor HVT. Metabolic and cardiorespiratory stress,
evidenced by blood lactate, HR, [Formula: see text], V E, and V E/[Formula: see
text] was higher during HIIT compared to HVT. CONCLUSION: The metabolic and
cardiorespiratory stress during HIIT was higher compared to HVT, but based on
salivary analyses (cortisol, testosterone, alpha-amylase), we conclude no strong
acute catabolic effects neither by HIIT nor by HVT.
PMID- 27614885
TI - Imaging of flank pain: readdressing state-of-the-art.
AB - Pain resulting from renal and ureteral stones is a common cause for patients
presenting in the acute setting. Since the late 1990s, computed tomography (CT)
has been the initial imaging method of choice to evaluate patients with suspected
ureteral stones; however, concerns regarding both radiation dose and cost
effectiveness have prompted investigations into a different imaging algorithm.
Studies utilizing ultrasound have provided evidence indicating that it may be a
more appropriate first step, with selective use of CT in selected cases, in the
diagnostic work-up. Techniques have evolved with low-dose CT, dual-energy CT, and
magnetic resonance urography emerging as useful in imaging of renal colic
patients. This manuscript reviews the current literature on state-of-the-art
imaging for acute flank pain and proposes a new imaging algorithm in the
evaluation of patients with acute flank pain and suspected ureteral stones.
PMID- 27614886
TI - Aberrant DNA methylation of alternative promoter of DLC1 isoform 1 in
meningiomas.
AB - DLC1 encodes GTPase-activating protein with a well-documented tumor suppressor
activity. This gene is downregulated in various tumors through aberrant promoter
hypermethylation. Five different DLC1 isoforms can be transcribed from
alternative promoters. Tumor-related DNA methylation of the DLC1 isoform 1
alternative promoter was identified as being hypermethylated in meningiomas in
genome-wide DNA methylation profiling. We determined the methylation pattern of
this region in 50 meningioma FFPE samples and sections of 6 normal meninges, with
targeted bisulfite sequencing. All histopathological subtypes of meningiomas
showed similar and significant increase of DNA methylation levels. High DNA
methylation was associated with lack of DLC1 protein expression in meningiomas as
determined by immunohistochemistry. mRNA expression levels of 5 isoforms of DLC1
transcript were measured in an additional series of meningiomas and normal
meninges. The DLC1 isoform 1 was found as the most expressed in normal control
tissue and was significantly downregulated in meningiomas. Transfection of KT21
meningioma cell line with shRNA targeting DLC1 isoform 1 resulted in increased
activation of RHO-GTPases assessed with pull-down assay, enhanced cell migration
observed in scratch assay as well as slight increase of cell metabolism determind
by MTT test. Results indicate that isoform 1 represents the main pool of DLC1
protein in meninges and its downregulation in meningiomas is associated with
hypermethylation of CpG dinucleotides within the corresponding promoter region.
This isoform is functional GAP protein and tumor suppressor and targeting of its
expression results in the increase of DLC1 related cell processes: RHO activation
and cell migration.
PMID- 27614887
TI - Parents as source of pertussis transmission in hospitalized young infants.
AB - PURPOSE: This study was planned to collect evidences of familial pertussis
transmission to infants younger than 6 months of age. Understanding the dynamics
of transmission of pertussis in families is essential to plan effective
prevention strategies that could be integrated in pertussis control. METHODS: The
seroprevalence of IgG antibodies to pertussis toxin (PT-IgG) and prolonged cough
symptoms were evaluated in parents of 55 infants aged <6 months hospitalized for
confirmed pertussis. Parents of 33 infants with lower respiratory tract infection
(LRTI) and parents of 57 healthy infants admitted as outpatients for hip
ultrasound examination (HE) were enrolled as controls. RESULTS: Parents of
pertussis cases had PT-IgG levels significantly higher as compared to LRTI and HE
parents. More than 40 % were compatible as transmitters of pertussis to their
babies, since they had a level of PT-IgG >= 100 IU/ml, which is considered
diagnostic for a recent pertussis episode. Based on serology, the percentage of
pertussis cases that had at least one parent as source of infection was 49.1 %.
When cough symptoms were taken into account, the percentage of parents putative
transmitters of the infection to their infants increased to 56.4 %. CONCLUSIONS:
Parents are scarcely aware of the household transmission of pertussis to their
newborns. Our study highlights the need to advise parents about the likelihood of
transmission to the newborn and to be particularly aware of coughing symptoms in
the household. Since infection can be asymptomatic, a serological survey of
family members should also be considered.
PMID- 27614889
TI - Association of Job Insecurity with Health Risk Factors and Poorer Health in
American Workers.
AB - Perceived job insecurity and health risk factors have not been well studied in
the United States (US) workforce. The purpose of this study was to assess the
association of specific health risk factors and morbidities with perceived job
insecurity in a large national random sample of working adults in the US. The
National Health Interview Survey data were analyzed for this study. We computed
the prevalence of perceived job insecurity by demographic characteristics and
tested the relative association between perceived job insecurity and selected
health risk factors using logistic regression analysis with adjusted odds ratios
(AORs). A total of 17,441 working adults were included in the study: 75 % Whites,
51.5 % females, 73.3 % worked for a private company, and 82.6 % were 25-64 years
of age. One in three (33 %) workers perceived their job to be insecure. Those who
reported job insecurity had significantly higher odds of: being obese, sleeping
less than 6 h/day, smoking every day, having work loss days >2 weeks, and
worsening of general health in the past year. Job insecure individuals had a
likelihood of serious mental illness within the past 30 days almost five times
higher than those who were not job insecure. In addition, job insecure
individuals were significantly more likely to report pain conditions (i.e.
headaches, neck pain, and low back pain), and lifetime histories of having
ulcers, diabetes, hypertension, angina pectoris, and coronary heart diseases. Job
insecurity is associated with poor health and health risk behaviors in American
adults. Potential interventions to address job insecurity and improve the health
and well-being of working adults have been discussed based on study findings.
PMID- 27614888
TI - Atorvastatin Modulates Regulatory T Cells and Attenuates Cerebral Damage in a
Model of Transient Middle Cerebral Artery Occlusion in Rats.
AB - Regulatory T cells (Tregs) inhibit the activation of the immune response which
could down-regulate the systemic and focal activation observed during ischemic
stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and
reduce the pro-inflammatory cytokine production and infarct volume, mainly in
late stages of ischemia. Recently, an expansion and greater suppressive capacity
of circulating Tregs after treatment with statins was observed, in addition to
their cardio- and neuroprotective actions demonstrated previously. Thus, to
determine whether Treg modulation mediated by statins can also be beneficial
during stroke, cerebral ischemia was artificially induced in Wistar rats by
transient middle cerebral artery occlusion (tMCAO) during 60 minutes with
subsequent reperfusion for 7 days. Six hours after surgery, some animals were
treated with atorvastatin (ATV, 10 mg/kg) or carboxymethylcellulose as vehicle at
the same concentration every other day during 7 days. Some animals were sham
operated as control group of surgery. Interestingly, ATV treatment prevented the
development of infarct volume, reduced the neurological deficits, and the
circulating and cervical lymph node CD25+FoxP3+ Treg population. Moreover, there
was a reduction of glial cell activation, which correlated with decreased
circulating Tregs. Remarkably, treatment with ATV induced an increase in the
frequency of CD4+CD25+ T cells, in particular of those expressing CTLA-4, in
brain samples. Together, these results suggest that ATV can modulate Tregs in
peripheral tissue and favor their accumulation in the brain, where they can exert
neuroprotective actions maybe by the reduction of glial cell activation.
PMID- 27614890
TI - Oral Health Beliefs, Attitudes, and Practices of Albanian Immigrants in the
United States.
AB - Research indicates a high prevalence of oral disease among Albanians. There is a
lack of evidence regarding oral health beliefs and practices among Albanian
immigrants in the United States and abroad. This research seeks to better
understand the oral health beliefs, attitudes, and practices among Albanian
immigrants living in the United States. A descriptive study was employed with a
purposive sample (n = 211) of Albanian adult immigrants. A cross-sectional
validated questionnaire was provided in both English and Albanian, with a
response rate of 66 %. Results revealed a high use of dental services among
respondents, with 68 % reported as having a dental visit and cleaning within the
past year. Although 25 % of participants stated their parents and grandparents
have used folk remedies, 88 % of them stated that use of folk remedies did not
influence their decision to seek professional dental care. Increasing age was
inversely associated with the belief in the importance of retaining natural
teeth, as older respondents were less likely to agree with the prior statement;
older respondents were more likely to agree with the statement "bleeding gums are
normal." Low oral health care access and utilization was not a factor among the
majority of the Albanian immigrants studied. Focusing on providing age
appropriate oral health education and behavioral strategies could increase oral
health knowledge and potentially improve poor oral health status among this
population.
PMID- 27614892
TI - The use of compensatory strategies in adults with ADHD symptoms.
AB - This study examined the use of compensatory strategies reported by adults with
ADHD symptoms and their relation to measures of functioning. Forty-nine adults
(55.1 % female) completed a structured diagnostic interview to assess ADHD, and
responses were coded for compensatory strategies: Adaptation, Paying Attention,
Organization, External Support, and Avoidance. The majority of adults with ADHD
symptoms reported using compensatory strategies, and their reported strategy use
in childhood was related to their use in adulthood. No gender differences were
found in the use of strategies, although Organization and External Support were
used more often for inattention than for hyperactive/impulsive symptoms. Use of
the compensatory strategy, Adaptation, was significantly related to measures of
functioning, and the use of strategies reduced the negative relationship between
ADHD symptoms and parenting difficulties. Results encourage the development of
compensatory strategies among adults with ADHD symptoms, as well as provide
recommendations for treatment programs.
PMID- 27614891
TI - Review: cornification, morphogenesis and evolution of feathers.
AB - Feathers are corneous microramifications of variable complexity derived from the
morphogenesis of barb ridges. Histological and ultrastructural analyses on
developing and regenerating feathers clarify the three-dimensional organization
of cells in barb ridges. Feather cells derive from folds of the embryonic
epithelium of feather germs from which barb/barbule cells and supportive cells
organize in a branching structure. The following degeneration of supportive cells
allows the separation of barbule cells which are made of corneous beta-proteins
and of lower amounts of intermediate filament (IF)(alpha) keratins, histidine
rich proteins, and corneous proteins of the epidermal differentiation complex.
The specific protein association gives rise to a corneous material with specific
biomechanic properties in barbules, rami, rachis, or calamus. During the
evolution of different feather types, a large expansion of the genome coding for
corneous feather beta-proteins occurred and formed 3-4-nm-thick filaments through
a different mechanism from that of 8-10 nm IF keratins. In the chick, over 130
genes mainly localized in chromosomes 27 and 25 encode feather corneous beta
proteins of 10-12 kDa containing 97-105 amino acids. About 35 genes localized in
chromosome 25 code for scale proteins (14-16 kDa made of 122-146 amino acids),
claws and beak proteins (14-17 kDa proteins of 134-164 amino acids). Feather
morphogenesis is periodically re-activated to produce replacement feathers, and
multiple feather types can result from the interactions of epidermal and dermal
tissues. The review shows schematic models explaining the translation of the
morphogenesis of barb ridges present in the follicle into the three-dimensional
shape of the main types of branched or un-branched feathers such as plumulaceous,
pennaceous, filoplumes, and bristles. The temporal pattern of formation of barb
ridges in different feather types and the molecular control from the dermal
papilla through signaling molecules are poorly known. The evolution and
diversification of the process of morphogenesis of barb ridges and patterns of
their formation within feathers follicle allowed the origin and diversification
of numerous types of feathers, including the asymmetric planar feathers for
flight.
PMID- 27614893
TI - Primary Amebic Meningoencephalitis: What Have We Learned in the Last 5 Years?
AB - Primary amebic meningoencephalitis (PAM) is a devastating infection of the brain
caused by the thermophilic free-living ameba, Naegleria fowleri. Infection can
occur when water containing the ameba enters the body through the nose, usually
during recreational water activities such as swimming or diving. Historically, in
the USA, cases were mostly reported from the warmer southern-tier states. In the
last 5 years, several notable changes have been documented in PAM epidemiology
including a northward expansion of infections and new types of water exposures.
The recent reports of two PAM survivors provide hope for improved outcomes with
early diagnosis and aggressive treatment. Advanced molecular laboratory tools
such as genome sequencing might provide more insight into the pathogenicity of N.
fowleri. Clinicians treating patients with meningitis and warm freshwater
exposure are encouraged to consider PAM in their differential diagnoses.
PMID- 27614894
TI - Characterising and comparing animal-health services in the Rift Valley, Kenya: an
exploratory analysis (part I).
AB - Livestock are of vital importance to the livelihoods of millions of people across
the world, playing a pivotal role in income generation, employment, food
security, transport and social cohesion. Access to quality animal-health services
by livestock owners is critical to sustainable food-animal production; therefore,
animal-health practitioners represent key stakeholders within the world food
system. A mixed-method study was conducted in the Rift Valley of Kenya to
characterise and compare existing private animal-health services and to explore
perceptions of veterinary services amongst pastoralists and farmers. Forty
structured questionnaires were administered to staff at animal-health outlets,
including franchise outlets of 'Sidai Africa Ltd.', and two focus group
discussions were facilitated to explore the perceptions of a Maasai pastoralist
group and members of a dairy-farmer cooperative of their local animal-health
services. Results were analysed using descriptive methods and the confidence
interval overlap technique. Differences were detected in the characteristics of
Sidai outlets, agrovets (agricultural retailers), pharmacies and dukas (general
shops). Sidai outlets offered a more professional and diverse portfolio of
livestock services. Across all outlet types, staff knowledge and training gaps
and a shortage of cold-chain facilities were identified. Farmers have strong
preferences for certain products, which may foster the development of drug
resistance. There is a disconnection between the sale of veterinary medicines and
the provision of quality advice, with many agrovets, pharmacies and dukas selling
veterinary medicines but lacking the capacity to provide clinical services. There
is a clear demand from livestock keepers for accessible, affordable and quality
animal-health services and products in Kenya; therefore, animal-health
practitioners have the potential to provide increased support to livestock-based
livelihoods.
PMID- 27614895
TI - Pramipexole induced place preference after L-dopa therapy and nigral dopaminergic
loss: linking behavior to transcriptional modifications.
AB - RATIONALE: Impulsive-compulsive disorders (ICD) in patients with Parkinson's
disease (PD) have been described as behavioral or substance addictions including
hypersexuality, gambling, or compulsive medication use of the dopamine
replacement therapy (DRT). OBJECTIVES: A remaining challenge is to understand the
neuroadaptations leading to reward bias in PD patients under DRT. METHODS: To
this end, the appetitive effect of the D2/D3 agonist pramipexole was assessed
after chronic exposure to L-dopa in an alpha-synuclein PD rat model. RESULTS:
Association of progressive nigral loss and chronic L-dopa was required to observe
a pramipexole-induced place preference. This behavioral outcome was inhibited by
metabotropic glutamate receptor 5 (mGluR5) antagonism while transcriptional
profiling highlighted regulations potentially related to the context of
psychostimulant addiction. CONCLUSION: This study provides evidences strongly
suggesting that PD-like lesion and L-dopa therapy were concomitant factors
involved in striatal remodeling underlying the pramipexole-induced place
preference. Molecular and pharmacological data suggest a key involvement of the
glutamatergic pathway in this behavioral outcome.
PMID- 27614897
TI - Expression pattern of circadian genes and steroidogenesis-related genes after
testosterone stimulation in the human ovary.
AB - BACKGROUND: Previous studies have shown that circadian genes might be involved in
the development of polycystic ovarian syndrome (PCOS). Hyperandrogenism is a
hallmark feature of PCOS. However, the effect of hyperandrogenism on circadian
gene expression in human granulosa cells is unknown, and the general expression
pattern of circadian genes in the human ovary is unclear. METHODS: Expression of
the circadian proteins CLOCK and PER2 in human ovaries was observed by
immunohistochemistry. The mRNA expression patterns of the circadian genes CLOCK,
PER2, and BMAL1, and the steroidogenesis-related genes STAR, CYP11A1, HSD3B2, and
CYP19A1 in cultured human luteinized granulosa cells were analyzed over the
course of 48 h after testosterone treatment by quantitative polymerase chain
reaction. RESULTS: Immunostaining of CLOCK and PER2 protein was detected in the
granulosa cells of dominant antral follicles but was absent in the primordial,
primary, or preantral follicles of human ovaries. After testosterone stimulation,
expression of PER2 showed an oscillating pattern, with two peaks occurring at the
24th and 44th hours; expression of CLOCK increased significantly to the peak at
the 24th hour, whereas expression of BMAL1 did not change significantly over time
in human luteinized granulosa cells. Among the four steroidogenesis-related genes
evaluated, only STAR displayed an oscillating expression pattern with two peaks
occurring at the 24th and 40th hours after testosterone stimulation. CONCLUSIONS:
Circadian genes are expressed in the dominant antral follicles of the human
ovary. Oscillating expression of the circadian gene PER2 can be induced by
testosterone in human granulosa cells in vitro. Expression of STAR also displayed
an oscillating pattern after testosterone stimulation. Our results indicate a
potential relationship between the circadian clock and steroidogenesis in the
human ovary, and demonstrate the effect of testosterone on circadian gene
expression in granulosa cells.
PMID- 27614898
TI - Development of a Larval Bioassay Method Using 96-Well Microtiter Plates for
Evaluation of Susceptibility of the Cat Fleas (Siphonaptera: Pulicidae) to
Insecticides.
PMID- 27614899
TI - Thymic oncocytic carcinoid with a markedly elevated level of maximum SUV.
PMID- 27614896
TI - Oxytocin modulates hemodynamic responses to monetary incentives in humans.
AB - RATIONALE: Oxytocin is a neuropeptide widely recognized for its role in
regulating social and reproductive behavior. Increasing evidence from animal
models suggests that oxytocin also modulates reward circuitry in non-social
contexts, but evidence in humans is lacking. OBJECTIVES: We examined the effects
of oxytocin administration on reward circuit function in 18 healthy men as they
performed a monetary incentive task. METHODS: The blood oxygenation level
dependent (BOLD) signal was measured using functional magnetic resonance imaging
in the context of a randomized, double-blind, placebo-controlled, crossover trial
of intranasal oxytocin. RESULTS: We found that oxytocin increases the BOLD signal
in the midbrain (substantia nigra and ventral tegmental area) during the late
phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on
midbrain responses correlated positively with its effects on positive emotional
state. We did not detect an effect of oxytocin on responses in the nucleus
accumbens. Whole-brain analyses revealed that oxytocin attenuated medial
prefrontal cortical deactivation specifically during anticipation of loss.
CONCLUSIONS: Our findings demonstrate that intranasal administration of oxytocin
modulates human midbrain and medial prefrontal function during motivated
behavior. These findings suggest that endogenous oxytocin is a neurochemical
mediator of reward behaviors in humans-even in a non-social context-and that the
oxytocinergic system is a potential target of pharmacotherapy for psychiatric
disorders that involve dysfunction of reward circuitry.
PMID- 27614900
TI - Electrophysiological evidence for parts and wholes in visual face memory.
AB - It is often assumed that upright faces are represented in a holistic fashion,
while representations of inverted faces are essentially part-based. To assess
this hypothesis, we recorded event-related potentials (ERPs) during a sequential
face identity matching task where successively presented pairs of upright or
inverted faces were either identical or differed with respect to their internal
features, their external features, or both. Participants' task was to report on
each trial whether the face pair was identical or different. To track the
activation of visual face memory representations, we measured N250r components
that emerge over posterior face-selective regions during the activation of visual
face memory representations by a successful identity match. N250r components to
full identity repetitions were smaller and emerged later for inverted as compared
to upright faces, demonstrating that image inversion impairs face identity
matching processes. For upright faces, N250r components were also elicited by
partial repetitions of external or internal features, which suggest that the
underlying identity matching processes are not exclusively based on non
decomposable holistic representations. However, the N250r to full identity
repetitions was super-additive (i.e., larger than the sum of the two N250r
components to partial repetitions of external or internal features) for upright
faces, demonstrating that holistic representations were involved in identity
matching processes. For inverted faces, N250r components to full and partial
identity repetitions were strictly additive, indicating that the identity
matching of external and internal features operated in an entirely part-based
fashion. These results provide new electrophysiological evidence for qualitative
differences between representations of upright and inverted faces in the
occipital-temporal face processing system.
PMID- 27614901
TI - Indications, technique, and results of robotic pancreatoduodenectomy.
AB - Robotic assistance improves surgical dexterity in minimally invasive operations,
especially when fine dissection and multiple sutures are required. As such,
robotic assistance could be rewarding in the setting of robotic
pancreatoduodenectomy (RPD). RPD was implemented at a high volume center with
preemptive experience in advanced laparoscopy. Indications, surgical technique,
and results of RPD are discussed against the background of current literature.
RPD was performed in 112 consecutive patients. Conversion to open surgery was
required in three patients, despite nine required segmental resection and
reconstruction of the superior mesenteric/portal vein. No patient was converted
to laparoscopy. A pancreato-jejunostomy was created in 106 patients (94.6 %),
using either a duct-to-mucosa (n = 82; 73.2 %) or an invaginating (n = 24; 21.4
%) technique. Pancreato-gastrostomy was performed in one patient, the pancreatic
duct was occluded in two patients, and a pancreatico-cutaneous fistula was
created in three patients. Mean operative time was 526.3 +/- 102.4 in the entire
cohort and reduced significantly over the course of time. Experience was also
associated with reduced rates of delayed gastric emptying and increased
proportion of malignant tumor histology. Ninety day mortality was 3.6 %.
Postoperative complications occurred in 83 patients (74.1 %) with a median
comprehensive complication index of 20.9 (0-30.8). Clinically relevant pancreatic
fistula occurred in 19.6 % of the patients. No grade C pancreatic fistula was
noted in the last 72 consecutive patients. RPD is safely feasible in selected
patients. Implementation of RPD requires sound experience with open
pancreatoduodenectomy and advanced laparoscopic procedures, as well as specific
training with the robotic platform.
PMID- 27614902
TI - Cost Effectiveness of the Earned Income Tax Credit as a Health Policy Investment.
AB - INTRODUCTION: Lower-income Americans are suffering from declines in income,
health, and longevity over time. Income and employment policies have been
proposed as a potential non-medical solution to this problem. METHODS: An
interrupted time series analysis of state-level incremental supplements to the
Earned Income Tax Credit (EITC) program was performed using data from 1993 to
2010 Behavioral Risk Factor Surveillance System surveys and state-level life
expectancy. The cost effectiveness of state EITC supplements was estimated using
a microsimulation model, which was run in 2015. RESULTS: Supplemental EITC
programs increased health-related quality of life and longevity among the poor.
The program costs about $7,786/quality-adjusted life-year gained (95% CI=$4,100,
$13,400) for the average recipient. This ratio increases with larger family
sizes, costing roughly $14,261 (95% CI=$8,735, $19,716) for a family of three.
CONCLUSIONS: State supplements to EITC appear to be highly cost effective, but
randomized trials are needed to confirm these findings.
PMID- 27614903
TI - The JAK2 V617F mutation in patients with anaemia.
PMID- 27614905
TI - Comparison of the efficacy of different treatment modalities for Kimura's
disease.
AB - The objective of this study was to investigate the clinical features of Kimura's
disease in the head and neck region and to compare the local recurrence rate
between three therapies used for the treatment of this disease. The
clinicopathological information of 46 hospitalized patients suffering from
Kimura's disease in the head and neck region over a 10-year period was reviewed
retrospectively. All lesions were clinically observed in the head and neck
region. These 46 patients underwent a total of 58 treatments; nine patients
underwent multiple treatments due to local recurrence. Of the 58 treatments, 32
involved surgical excision alone, 24 involved surgical excision and postoperative
low-dose radiotherapy (20-40Gy), one was a combination of ultrasound-guided core
needle biopsy and radiotherapy, and one was a combination of incisional biopsy
and subsequent radiotherapy. During the follow-up period, nine patients suffered
16 local recurrences. The recurrence rate of surgical excision combined with low
dose radiotherapy was much lower than that of surgical excision alone or
radiotherapy alone (both P<0.05). It is concluded that Kimura's disease is a
benign condition with a good prognosis, and surgical excision combined with
postoperative low-dose radiotherapy is associated with the lowest local
recurrence rate in the treatment of this disease.
PMID- 27614904
TI - Quantifying the pediatric surgical need in Uganda: results of a nationwide cross
sectional, household survey.
AB - PURPOSE: Little is known about the prevalence of pediatric surgical conditions in
low- and middle-income countries. Many children never seek medical care, thus the
true prevalence of surgical conditions in children in Uganda is unknown. The
objective of this study was to determine the prevalence of surgical conditions in
children in Uganda. METHODS: Using the Surgeons OverSeas Assessment of Surgical
Need (SOSAS) survey, we enumerated 4248 individuals in 2315 households in 105
randomly selected clusters throughout Uganda. Children aged 0-18 were included if
randomly selected from the household; for those who could not answer for
themselves, parents served as surrogates. RESULTS: Of 2176 children surveyed, 160
(7.4 %) reported a currently untreated surgical condition. Lifetime prevalence of
surgical conditions was 14.0 % (305/2176). The predominant cause of surgical
conditions was trauma (48.4 %), followed by wounds (19.7 %), acquired deformities
(16.2 %), and burns (12.5 %). Of 90 pediatric household deaths, 31.1 % were
associated with a surgically treatable proximate cause of death (28/90 deaths).
CONCLUSION: Although some trauma-related surgical burden among children can be
adequately addressed at district hospitals, the need for diagnostics, human
resources, and curative services for more severe trauma cases, congenital
deformities, and masses outweighs the current capacity of hospitals and trained
pediatric surgeons in Uganda.
PMID- 27614906
TI - Three-dimensional cone beam computed tomography analysis of maxillary sinus and
alveolar bone anatomy in the restorative axis of dental implants using radiopaque
drill guides.
AB - The objectives were to assess the sinus anatomy and alveolar ridge dimensions and
to identify clinical factors and morphological relationships that may predict the
characteristics of the sinus anatomy. A total 336 edentulous molar and 168
edentulous premolar regions were analyzed. The mediolateral maxillary sinus (5mm
and 10mm above alveolar bone), lateral maxillary sinus wall, ostium height, and
alveolar ridges were measured. Measurement regions were defined by radiopaque
simulation of the restoration goal. Mean molar mediolateral dimensions were
>10mm: first molar, 11.8mm (range 3.8-21.1mm); second molar, 12.2mm (range 7.9
20.1mm). The extent of the sinus differed significantly between premolars and
molars (P<0.001). The first molar region had the highest mean value for the
lateral sinus wall (2.4mm, range 0.2-7.9mm) and the greatest distance between the
alveolar crest and simulated restorative goal (8.1mm, range 1.1-16.3mm). Septum
prevalence was 46% in the molar region and 27% in the premolar region. A lower
alveolar ridge height was associated with a wider transverse extent of maxillary
sinus and consequently longer distances between the crest and restorative goal.
Systematic three-dimensional analysis of the maxillary sinus yields precise
preoperative information about sinus configurations. There were significant
variations and relationships among characteristics of the maxillary sinus, ridge,
and the restorative goal.
PMID- 27614907
TI - "My heart burns" - A qualitative study of perceptions and experiences of type 1
diabetes among children and youths in Tajikistan.
AB - Aims To explore and describe perceptions and experiences of living with type 1
Diabetes Mellitus among children/youths in Tajikistan. Methods Qualitative
methods were employed. Participants were recruited through purposive and snowball
samplings. Data were collected using a semi-structured interview guide with
children/youths having diabetes, their parents as well as health professionals.
Data were analyzed according to Malterud's systematic text condensation. Results
Children/youths with diabetes (n = 18), their parents (n = 19) and
endocrinologists (n = 4) were interviewed. Families described unique stories in
which "emotional stress" and a spiritual "evil eye" were perceived as possible
causes of diabetes. Life-threatening complications and maltreatment preceding
diagnosis of diabetes were frequent. From manifestation of diabetes onwards,
families struggled with systemic and cultural obstacles, causing stigma,
discrimination, high school-drop-out rates, diabetic coma, chronic complications
or death of the child/youth with diabetes. Conclusions Results of this
qualitative study highlight the severity and complexity of challenges families
living with a child/youth having diabetes in this low-income country face.
Efforts to improve life expectancy and life quality are strongly needed and
require addressing both systemic and cultural factors in order to accomplish
sustainable impact.
PMID- 27614908
TI - Comparison of pollution indices for the assessment of heavy metal in Brisbane
River sediment.
AB - Estuarine environment is complex and receives different contaminants from
numerous sources that are persistent, bioaccumulative and toxic. The
distribution, source, contamination and ecological risk status of heavy metals in
sediment of Brisbane River, Australia were investigated. Sediment samples were
analysed for major and minor elements using LA-ICP-MS. Principal component
analysis and cluster analysis identified three main sources of metals in the
samples: marine sand intrusion, mixed lithogenic and sand intrusion as well as
transport related. To overcome inherent deficiencies in using a single index, a
range of sediment quality indices, including contamination factor, enrichment
factor, index of geo-accumulation, modified degree of contamination, pollution
index and modified pollution index were utilised to ascertain the sediment
quality. Generally, the sediment is deemed to be "slightly" to "heavily"
polluted. A further comparison with the Australian Sediment Quality Guidelines
indicated that Ag, Cr, Cu, Ni, Pb and Zn had the potential to rarely cause
biological effects while Hg could frequently cause biological effects.
Application of potential ecological risk index (RI) revealed that the sediment
poses moderate to considerable ecological risk. However, RI could not account for
the complex sediment behaviour because it uses a simple contamination factor.
Consequently, a modified ecological risk index (MRI) employing enrichment factor
is proposed. This provides a more reliable understanding of whole sediment
behaviour and classified the ecological risk of the sediment as moderate to very
high. The results demonstrate the need for further investigation into heavy metal
speciation and bioavailability in the sediment to ascertain the degree of
toxicity.
PMID- 27614909
TI - The Tradescantia micronucleus assay is a highly sensitive tool for the detection
of low levels of radioactivity in environmental samples.
AB - Environmental contamination with radioactive materials of geogenic and
anthropogenic origin is a global problem. A variety of mutagenicity test
procedures has been developed which enable the detection of DNA damage caused by
ionizing radiation which plays a key role in the adverse effects caused by
radioisotopes. In the present study, we investigated the usefulness of the
Tradescantia micronucleus test (the most widely used plant based genotoxicity
bioassay) for the detection of genetic damage caused by environmental samples and
a human artifact (ceramic plate) which contained radioactive elements. We
compared the results obtained with different exposure protocols and found that
direct exposure of the inflorescences is more sensitive and that the number of
micronuclei can be further increased under "wet" conditions. The lowest dose rate
which caused a significant effect was 1.2 MUGy/h (10 h). Comparisons with the
results obtained with other systems (i.e. with mitotic cells of higher plants,
molluscs, insects, fish and human lymphocytes) show that the Tradescantia MN
assay is one to three orders of magnitude more sensitive as other models, which
are currently available. Taken together, our findings indicate that this method
is due to its high sensitivity a unique tool, which can be used for environmental
biomonitoring in radiation polluted areas.
PMID- 27614910
TI - Environmental concentrations of prednisolone alter visually mediated responses
during early life stages of zebrafish (Danio rerio).
AB - The development of the eye in vertebrates is dependent upon glucocorticoid
signalling, however, specific components of the eye are sensitive to synthetic
glucocorticoids. The presence of synthetic glucocorticoids within the aquatic
environment may therefore have important consequences for fish, which are heavily
reliant upon vision for mediating several key behaviours. The potential
ethological impact of synthetic glucocorticoid oculotoxicity however has yet to
be studied. Physiological and behavioural responses which are dependent upon
vision were selected to investigate the possible toxicity of prednisolone, a
commonly occurring synthetic glucocorticoid within the environment, during early
life stages of zebrafish. Although exposure to prednisolone did not alter the
morphology of the external eye, aggregation of melanin within the skin in
response to increasing light levels was impeded and embryos exposed to
prednisolone (10 MUg/l) maintained a darkened phenotype. Exposure to prednisolone
also increased the preference of embryos for a dark environment within a light
dark box test in a concentration dependent manner. However the ability of embryos
to detect motion appeared unaffected by prednisolone. Therefore, while
significant effects were detected in several processes mediated by vision,
changes occurred in a manner which suggest that vision was in itself unaffected
by prednisolone. Neurological and endocrinological changes during early ontogeny
are considered as likely candidates for future investigation.
PMID- 27614911
TI - Determining exhaust fumes exposure in chainsaw operations.
AB - The objective of this study was to investigate the inhalation exposure of forest
operators to polycyclic aromatic hydrocarbons (PAHs) and BTEX (benzene, toluene,
ethylbenzene and total xylenes) contained in the exhaust fumes released from
chainsaws and to suggest possible countermeasures. The study was carried out in
four silvicultural treatments (coppice clearcut, conifer thinning, conifer
pruning, and sanitary cut), using three types of chainsaw fuel (normal two-stroke
petrol mix and two alkylate fuels). Eighty personal air samples were collected;
IOM samplers combined with Amberlite XAD-2 sorbent tubes were used for collecting
PAHs and Radiello(r) samplers were used for BTEX. Results indicate that none of
the four silvicultural treatments significantly affected the PAHs and BTEX
inhalation exposure of forest workers. On the other hand, statistically
significant differences were recorded in the inhalation exposure to PAHs and BTEX
when using different fuel types. In particular, the inhalation exposure to PAHs
and BTEX was generally one order of magnitude lower when using modern alkylate
fuels as compared to the traditional oil and lead-free petrol mixture. The small,
non-statistically significant differences in inhalation exposure recorded between
the two alkylate fuels suggests that the two fuels might be equivalent in terms
of quality. Our study indicates that while forest workers are exposed to PAHs and
BTEX, the maximum values are generally well below accepted occupational exposure
limits.
PMID- 27614913
TI - Principles of Anti-infective Dosing in Pregnancy.
AB - PURPOSE: Anti-infectives are among the most commonly prescribed medications in
pregnancy. However, detailed information on the pharmacokinetics and
pharmacodynamics of these medications in pregnancy is limited, leading to
uncertainty among clinicians regarding the tolerability and efficacy of
treatments. The purposes of this review were to highlight key physiologic changes
during pregnancy that influence drug behavior, and to discuss areas of active
research related to anti-infective drugs in pregnancy. METHODS: A review of
literature in PubMed was performed for topics related to physiologic changes of
pregnancy, postcesarean surgical site infections, vaccines in pregnancy, and
intrauterine infections. The literature was reviewed and pertinent sources were
utilized for this article. FINDINGS: Physiologic changes during pregnancy may
impact drug disposition and efficacy. Cefazolin regimens are the current
prophylactic treatment of choice for postcesarean surgical site infections.
Vaccines are provided in pregnancy for both maternal and neonatal benefit. Broad
spectrum antibiotics continue to be used as first-line therapy for intrauterine
infections. IMPLICATIONS: Continued efforts to broaden the knowledge base on anti
infective drug behavior in pregnancy will result in increased therapeutic options
for this population.
PMID- 27614914
TI - Conformational and electrostatic analysis of SN1 donor analogue glycomimetic
inhibitors of ST3Gal-I mammalian sialyltransferase.
AB - Mammalian sialyltransferases play a role in the metastasis of various cancers in
humans. Inhibitors of these enzymes will in principle be able to directly inhibit
aberrant sialylation in cancer. Inhibitors of ST3Gal-I resembling the donor
component of SN1 Transition State structures were previously evaluated as part of
a kinetics study. Here, using classical dynamics simulations and free energy
perturbation calculations, we rationalize the performance of three of these donor
analogue ST3Gal-I enzyme inhibitors. We find to inhibit the mammalian ST3Gal-I
enzyme a donor analogue requires configurationally limited functionality. This is
mediated by the binding of the inhibitor to the enzyme. The inhibitor's ability
to interact with Y194 and T272 through a charged group such as a carboxylate is
especially important. Furthermore, a conformational rigid form approximating the
donor substrate is central. Here this is achieved by an intramolecular hydrogen
bond formed between the carboxylate group and one of the ribose hydroxyl groups
of the cytidine monophosphate (CMP) leaving group. This intramolecular
interaction results in the donor substrate conformer complimenting the form of
the catalytic binding site. Finally the carboxylate charge is essential for
electrostatic pairing with the binding site. Substituting this group for an
alcohol or amide results in severe weakening of the ligand binding. The
carboxylate thus proves an to be an irreplaceable functional group and an
essential pharmacophore.
PMID- 27614912
TI - A Phase I Study to Investigate the Absorption, Pharmacokinetics, and Excretion of
[(14)C]Prucalopride After a Single Oral Dose in Healthy Volunteers.
AB - PURPOSE: Chronic constipation is a prevalent gastrointestinal disorder globally.
It is often treated with medications such as laxatives. Newer therapies to
improve gastric motility include the selective 5-hydroxytryptamine receptor-4
agonist prucalopride, which is licensed for the treatment of chronic constipation
in adults. The aim of this study was to investigate the pharmacokinetic
properties and excretion of prucalopride in healthy individuals, using a
microtracer approach with (14)C radioactivity detection using liquid
scintillation counting and accelerator mass spectrometry. METHODS: This was a
single-period, open-label, nonrandomized absorption, metabolism, and excretion
study of [(14)C]prucalopride. Participants were 6 healthy men aged 18 to 50
years. After screening, participants were administered a single dose of
[(14)C]prucalopride succinate 2 mg (~200 nCi). Postadministration, urine, feces,
and blood samples were collected over a 10-day period. Safety and adverse event
data were also collected. FINDINGS: Almost 100% of the administered dose of
radioactivity was recovered, with a mean (SD) of 84.2% (8.88%) recovered in urine
and 13.3% (1.73%) recovered in feces. The mean blood-to-plasma concentration
ratio of 1.9 indicated uptake of prucalopride into blood cells. The renal
clearance of prucalopride was 17.0 (2.5) L/h, which is higher than the glomerular
filtration rate in healthy individuals, suggesting active renal transport of
prucalopride. Prucalopride was well tolerated, with no serious adverse events
reported. IMPLICATIONS: Prucalopride was well absorbed and excreted mainly by the
kidneys, including both passive and active transporter mechanisms. Quantitative
recovery of the radioactive dose was achieved. Consistent with previous studies,
prucalopride was generally well tolerated. ClinicalTrials.gov identifier:
NCT01807000.
PMID- 27614915
TI - Plazomicin is effective in a non-human primate pneumonic plague model.
AB - The efficacy of plazomicin for pneumonic plague was evaluated in a non-human
primate model. African Green monkeys challenged with a lethal aerosol of Yersinia
pestis [median (range) of 98 (15-331) LD50s] received placebo (n=12) or
'humanized' dose regimens (6.25, 12.5 or 25mg/kg every 24h) of plazomicin (n=52)
after the onset of fever for a duration of 5 or 10days. All animals treated with
placebo died, while 36 plazomicin-treated animals survived through study end. The
majority (33/36) were either in the 10-day (high-/mid-/low-dose) or 5-day high
dose groups. The findings suggest an exposure range of plazomicin for treatment
of pneumonic/bacteremic Y. pestis infection in humans.
PMID- 27614916
TI - Synthesis, biological evaluation and molecular docking study of N
arylbenzo[d]oxazol-2-amines as potential alpha-glucosidase inhibitors.
AB - A novel series of N-arylbenzo[d]oxazol-2-amines (4a-4m) were synthesized and
evaluated for their alpha-glucosidase inhibitory activity. Compounds 4f-4i, 4k
and 4m displayed potent inhibitory activity against alpha-glucosidase with IC50
values in the range of 32.49+/-0.17-120.24+/-0.51MUM as compared to the standard
drug acarbose. Among all tested compounds, compound 4g having 4-phenoxy
substitution at the phenyl ring was found to be the most active inhibitor of
alpha-glucosidase with an IC50 value of 32.49+/-0.17MUM. Analysis of the kinetics
of enzyme inhibition indicated that compound 4g is a noncompetitive inhibitor of
alpha-glucosidase with a Ki value of 31.33MUM. Binding interaction of compound 4g
with alpha-glucosidase was explored by molecular docking simulation.
PMID- 27614917
TI - Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti
tuberculosis agents.
AB - We report the design and synthesis of a series of non-nucleoside MtbTMPK
inhibitors (1-14) based on the gram-positive bacterial TMPK inhibitor hit
compound 1. A practical synthesis was developed to access these analogues.
Several compounds show promising MtbTMPK inhibitory potency and allow the
establishment of a structure-activity relationship, which is helpful for further
optimization.
PMID- 27614918
TI - Blood-brain barrier permeability of ginkgolide: Comparison of the behavior of PET
probes 7alpha-[18F]fluoro- and 10-O-p-[11C]methylbenzyl ginkgolide B in monkey
and rat brains.
AB - The blood-brain barrier permeability of ginkgolide B was examined using positron
emission tomography (PET) probes of a 18F-incorporated ginkgolide B ([18F]-2) and
a 11C-incorporated methylbenzyl-substituted ginkgolide B ([11C]-3). PET studies
in monkeys showed low uptake of [18F]-2 into the brain, but small amounts of
[11C]-3 were accumulated in the parenchyma. Furthermore, when cyclosporine A was
preadministered to rats, the accumulation of [18F]-2 in the rat brain did not
significantly change, however, the accumulation of [11C]-3 was five times higher
than that in the control rat. These results provide effective approaches for
investigating the drug potential of ginkgolides.
PMID- 27614919
TI - Synthesis and biological evaluation of santacruzamate A analogues for anti
proliferative and immunomodulatory activity.
AB - Santacruzamate A (SCA) is a natural product isolated from a Panamanian marine
cyanobacterium, previously reported to have potent and selective histone
deacetylase (HDAC) activity. To optimize the enzymatic and cellular activity, 40
SCA analogues were synthesized in a systematic exploration of the zinc-binding
group (ZBG), cap terminus, and linker region. Two cap group analogues inhibited
proliferation of MCF-7 breast cancer cells, with analogous increased
degranulation of cytotoxic T cells (CTLs), while one cap group analogue reduced
CTL degranulation, indicative of suppression of the immune response. Additional
testing of these analogues resulted in reevaluation of the previously reported
SCA mechanism of action. These analogues and the resulting structure-activity
relationships will be of interest for future studies on cell proliferation and
immune modulation.
PMID- 27614920
TI - Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[18F]fluoro-beta-d
allofuranosyl)-2-nitroimidazole (beta-6'-[18F]FAZAL) as a positron emission
tomography radiotracer to assess tumor hypoxia.
AB - Positron emission tomography (PET) using fluorine-18 (18F)-labeled 2
nitroimidazole radiotracers has proven useful for assessment of tumor
oxygenation. However, the passive diffusion-driven cellular uptake of currently
available radiotracers results in slow kinetics and low tumor-to-background
ratios. With the aim to develop a compound that is actively transported into
cells, 1-(6'-deoxy-6'-[18F]fluoro-beta-d-allofuranosyl)-2-nitroimidazole (beta
[18F]1), a putative nucleoside transporter substrate, was synthetized by
nucleophilic [18F]fluoride substitution of an acetyl protected labeling precursor
with a tosylate leaving group (beta-6) in a final radiochemical yield of 12+/-8%
(n=10, based on [18F]fluoride starting activity) in a total synthesis time of
60min with a specific activity at end of synthesis of 218+/-58GBq/MUmol (n=10).
Both radiolabeling precursor beta-6 and unlabeled reference compound beta-1 were
prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-alpha-d
allofuranose. In vitro experiments demonstrated an interaction of beta-1 with
SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific
retention of beta-[18F]1 in tumor cell lines. In biodistribution studies in
healthy mice beta-[18F]1 showed homogenous tissue distribution and excellent
metabolic stability, which was unaffected by tissue oxygenation. PET studies in
tumor bearing mice showed tumor-to-muscle ratios of 2.13+/-0.22 (n=4) at 2h after
administration of beta-[18F]1. In ex vivo autoradiography experiments beta-[18F]1
distribution closely matched staining with the hypoxia marker pimonidazole. In
conclusion, beta-[18F]1 shows potential as PET hypoxia radiotracer which merits
further investigation.
PMID- 27614921
TI - En bloc Excision and Matched Metatarsal Transfer for Expansive Benign Osteolytic
Lesions of the Metacarpal.
AB - PURPOSE: Benign aggressive expansile osteolytic lesions such as giant cell tumors
and aneurysmal bone cysts involving the metacarpal head pose problems in
management. Unacceptably high rates of recurrence are reported after curettage
and bone grafting. An en bloc excision of such tumors ideally requires
osteoarticular replacement of the excised metacarpal heads to retain mobility and
function. We used nonvascularized metatarsal head and shaft harvested from the
foot to replace the metacarpal defect after en bloc resection to retain movement
and function of metacarpophalangeal (MCP) joint. The purpose of this study was to
evaluate results of patients who underwent this procedure. METHOD: Nine patients
treated with metatarsal transfer for osteoarticular reconstruction after en bloc
excision of benign aggressive osteolytic metacarpal head tumors were reviewed
retrospectively. The postoperative evaluation included examination of
radiographs, joint mobility, and patient rated return of function using the
Michigan Hand Questionnaire. RESULTS: Of 9 patients, 4 had aneurysmal bone cyst,
4 had giant cell tumor, and 1 an atypical cartilaginous lesion. Patients were
aged between 14 and 45 years at the time of surgery. After an average of 44
months of follow-up (minimum follow-up of 24 months; range, 24-104 months), all
patients had good postoperative function, satisfactory results, and no recurrence
of tumor. The mean active range of motion at the reconstructed MCP joint was 75
degrees (range, 0 degrees to 90 degrees ). The Michigan Hand Questionnaire
score averaged 80 (range, 69-92). No patient complained of donor site morbidity.
One patient underwent MCP joint fusion after a pin tract infection. CONCLUSIONS:
Use of a matched metatarsal graft for osteoarticular reconstruction after en bloc
excision of benign aggressive tumors involving the metacarpal head is a potential
treatment option. In this limited series, consistent results with respect to
functional range of motion at MCP joint, and without recurrence of tumor or
notable donor site morbidity were obtained. TYPE OF STUDY/LEVEL OF EVIDENCE:
Therapeutic IV.
PMID- 27614922
TI - Neural Representation of Subjective Sexual Arousal in Men and Women.
AB - INTRODUCTION: Studies investigating brain indices of sexual arousal have begun to
elucidate the brain's role in processing subjective arousal; however, most
research has focused on men, used discrete ratings of subjective arousal, and
used stimuli too short to induce significant arousal in women. AIM: To examine
brain regions modulated by changes in subjective sexual arousal (SSA) rating
intensity in men and women. METHODS: Two groups (20 men, 20 women) viewed movie
clips (erotic or humorous) while continuously evaluating changes in their SSA
using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering
discrete questions about liking the movies and wanting sexual stimulation. Brain
activity was measured using functional magnetic resonance imaging. MAIN OUTCOME
MEASURES: Blood oxygen level-dependent responses and continuous and discrete
measurements of sexual arousal. RESULTS: Erotic movies induced significant SSA in
men and women. No sex difference in mean SSA was found in response to the erotic
movies on continuous or discrete measurements. Several brain regions were
correlated with changes in SSA. Parametric modulation with rating intensity
showed a specific group of regions within the parietal lobe that showed
significant differences in activity among low, medium, and high SSA. CONCLUSION:
Multiple regions were concordant with changes in SSA; however, a subset of
regions in men and women was modulated by SSA intensity, a subset previously
linked to attentional processes, monitoring of internal body representation, and
processing of sensory information from the genitals. This study highlights that
similar brain regions are activated during subjective assessment of sexual
arousal in men and women. The data further highlight the fact that SSA is a
complex phenomenon made up of multiple interoceptive and attentional processes.
PMID- 27614924
TI - Effect of liquid helium vitrification on the ultrastructure and related gene
expression of mature bovine oocytes after vitrifying at immature stage.
AB - This study aimed to investigate the developmental potential of and the
ultrastructural changes and gene expression differences resulting from liquid
helium (LHe; -269 degrees C) vitrification in immature bovine oocytes. Immature
oocytes were randomly divided into three groups: fresh oocytes (control, negative
control), oocytes vitrified in liquid nitrogen (LN group, positive control), and
oocytes vitrified in LHe (LHe group). In experiment 1, the rates of normal
morphology, maturation, cleavage, and blastocyst in the LHe group were higher
than those in the LN group (87.1% vs. 80.5%, 51% vs. 48%, 41.7% vs. 36.8%, and
13% vs. 8.5%, respectively; P < 0.05), and the rates of development in the
control group (100%, 73.2%, 62%, and 39.8%) were higher than those in the treated
groups (P < 0.05). In experiment 2, oocytes displayed various degrees of injury
at the ultrastructural level after vitrification, but more severe degeneration
was observed in the LN group, such as formation of several lipid droplets,
swelling of mitochondria, and absence of cortical granules. Compared with the LN
group, fewer lipid droplets, relatively intact mitochondria, and clustered
cortical granules were distributed in the cytoplasm of oocytes in the LHe group.
In experiment 3, the mRNA expression levels of p53, CDC20, Eg5, and Npm2 were
investigated by real-time quantitative polymerase chain reaction. Expression
levels of the kinesin Eg5 and the apoptotic gene p53 expression levels were
higher in the LN group compared with the control and LHe groups (P < 0.05). CDC20
and Npm2 expression did not differ significantly between the LN and LHe groups (P
> 0.05), the CDC20 expression in the LN and LHe groups were lower than control
group (P < 0.05), the Npm2 expression in LHe group was lower than control group
(P < 0.05), but there was no significant difference between the LN and control
groups (P > 0.05). In conclusion, LHe vitrification decreased the negative effect
of cryoinjury on the ultrastructure of some organelles and the expression of some
related genes, thereby improving the viability of immature bovine oocytes
compared to LN vitrification.
PMID- 27614923
TI - Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic
hypotension.
AB - The long-term safety of droxidopa for the treatment of symptomatic neurogenic
orthostatic hypotension in patients with Parkinson disease, pure autonomic
failure, multiple system atrophy, or nondiabetic autonomic neuropathy was
evaluated in a phase 3, multinational, open-label study in patients who
previously participated in a double-blind, placebo-controlled clinical trial of
droxidopa. A total of 350 patients received droxidopa 100 to 600 mg three times
daily. Mean duration of droxidopa exposure was 363 days (range, 2-1133 days).
Rates of serious adverse events (AEs), cardiac-related AEs, and supine
hypertension were 24%, 5%, and 5%, respectively. Most AEs, including those of a
cardiovascular nature, were not attributed by investigators to droxidopa. In this
large cohort of patients with neurogenic orthostatic hypotension, droxidopa was
well tolerated during long-term use.
PMID- 27614926
TI - The biomechanical and physiological response to repeated soccer-specific
simulations interspersed by 48 or 72 hours recovery.
AB - PURPOSE: To assess the residual fatigue response associated with the completion
of two successive soccer-specific exercise protocols (SSEP). METHODS: Twenty male
soccer players were pair-matched before completing SSEPs, interspersed by either
48 or 72 h. Outcome variables were measured every 15 min, and comprised uni-axial
measures of PlayerLoad, mean (HR) and peak heart rate (HRpeak), blood lactate
concentration, mean and peak (VO2peak) oxygen consumption, and rating of
perceived exertion (RPE). RESULTS: No significant (P > 0.05) group interactions
were identified for any outcome variables. Uni-axial (and total) PlayerLoad
exhibited a significant (P < 0.05) main effect for time, with the exception of
the relative contribution of medial lateral PlayerLoadTM. Total PlayerLoad during
the final 15 min (222.23 +/- 15.16 a.u) was significantly higher than all other
time points. All other outcome variables also exhibited a significant main effect
for time, with HR, HRpeak and VO2peak also exhibiting significantly higher values
in the first trial. There was also a significant (P = 0.003) trial*time
interaction for RPE. CONCLUSIONS: With equivalence at baseline, there was no
difference in the fatigue response associated with two SSEPs interspersed by
either 48 or 72 h recovery. The current study has implications for the design and
micro management of training and competition schedules.
PMID- 27614927
TI - External fixation versus dynamic hip screw in treatment of elderly
intertrochanteric hip fractures: A systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the effect of external fixation compared with dynamic hip
screw (DHS) for the treatment of elderly intertrochanteric hip fractures.
METHODS: We searched Pubmed, Embase, Cochrane central database (All to December
19th, 2015) for comparative studies relevant to external fixation versus DHS for
the management of intertrochanteric hip fractures. Only randomized controlled
trial (RCT) were included. We extracted the trial characteristics, intervention
details, primary and secondary outcomes. Risk of bias was assessed. Fixed/random
effect model was adapted according to the heterogeneity tested by I2 statistic.
Sensitivity analysis was conducted and publication bias was assessed. RESULTS: A
total of 4 RCTs were retrieved involving 260 patients. Pooled results showed for
the primary outcomes of Harris hip score and final mortality, no significant
difference was found between external fixation and DHS, however, for the
secondary outcomes, external fixation had advantages in the aspects of length of
surgery, operative blood loss, blood transfusion and hospital stay while
shortcomings in pin-track infection. For other secondary outcomes such as
fracture reduction, cut out and varus malunion, no significant difference could
be found. CONCLUSIONS: While there was no conclusive evidence, as external
fixation with less surgery time, less blood loss and less post-operative pain
while no compromise in final functional outcome and mortality compared with DHS,
it could be considered as an alternative for the elderly intertrochanteric hip
fractures, especially in highrisk patients who could not tolerate routine spinal
anesthesia and open surgery.
PMID- 27614925
TI - Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity.
AB - Pregnancy-associated malaria, including placental malaria, causes significant
morbidity and mortality worldwide. Recently, it has been suggested that in utero
exposure of the fetus to malaria antigens may negatively impact the developing
immune system and result in tolerance to malaria. Here, we review our current
knowledge of fetal immunity to malaria, focusing on the dynamic interactions
between maternal malaria infection, placental development, and the fetal immune
system. A better understanding of the long-term impact of in utero malaria
exposure on the development of natural immunity to malaria, immune responses to
other childhood pathogens, and vaccine immunogenicity is urgently needed. This
may guide the implementation of novel chemoprevention strategies during pregnancy
and facilitate the push toward malaria vaccines.
PMID- 27614928
TI - [In-depth interviews and the Kano model to determine user requirements in a burns
unit].
AB - OBJECTIVE: To determine the healthcare requirements of patients in a Burns Unit,
using qualitative techniques, such us in-depth personal interviews and Kano's
methodology. MATERIAL AND METHODS: Qualitative methodology using in-depth
personal interviews (12 patients), Kano's conceptual model, and the SERVQHOS
questionnaire (24 patients). All patients had been hospitalised in the last 12
months in the Burns Unit. Using Kano's methodology, service attributes were
grouped by affinity diagrams, and classified as follows: must-be, attractive
(unexpected, great satisfaction), and one-dimensional (linked to the degree of
functionality of the service). The outcomes were compared with those obtained
with SERVQHOS questionnaire. RESULTS: From the analysis of in-depth interviews,
11 requirements were obtained, referring to hotel aspects, information, need for
closer staff relationship, and organisational aspects. The attributes classified
as must-be were free television and automatic TV disconnection at midnight. Those
classified as attractive were: individual room for more privacy, information
about dressing change times in order to avoid anxiety, and additional staff for
in-patients. The results were complementary to those obtained with the SERVQHOS
questionnaire. CONCLUSIONS: In-depth personal interviews provide extra knowledge
about patient requirements, complementing the information obtained with
questionnaires. With this methodology, a more active patient participation is
achieved and the companion's opinion is also taken into account.
PMID- 27614929
TI - [A multimodal strategy to improve adherence to hand hygiene in a university
hospital].
AB - OBJECTIVE: Within the framework of the PaSQ (Patient Safety and Quality care)
Project, this hospital decided to implement a multifaceted hospital-wide Hand
Hygiene (HH) intervention based on a multimodal WHO approach over one year,
focusing on achieving a sustained change in HH cultural change in this hospital.
MATERIAL AND METHODS: Setting: University Hospital Marques de Valdecilla,
Santander (Spain), a tertiary hospital with 900 beds. Intervention period: 2014.
An action plan was developed that included the implementation of activities in
each component of the 5-step multimodal intervention. An observation/feedback
methodology was used that included the provision of performance and results
feedback to the staff. A 3/3 strategy (non-blinded direct observation audits
performed during 3 randomised days every 3 weeks with pro-active corrective
actions at the end of each observation period). HH compliance, alcohol-based hand
rub (ABHR) consumption, and rate of MRSA infection, were monitored during the
intervention. RESULTS: Hospital ABHR consumption increased during the study
period: from 17.5 to 19.7mL/patient-days. In the intervention units, this
consumption was 24.8mL pre-intervention, 42.5mL during the intervention, and
30.4mL two months post-intervention. There were 137 evaluation periods in 30
different days, in which a total of 737 health-care workers were observed and
1,870 HH opportunities. HH compliance was 54.5%, ranging between 44.8% and 69.9%.
The incidence of MRSA infection decreased during the intervention in the selected
units, from 13.2 infections per 10,000 patient-days pre-intervention to 5.7 three
months post-intervention. CONCLUSIONS: Our HH strategy, supported by a 3/3
strategy increased alcohol-based hand-rub consumption and compliance. A reduction
in MRSA infections was observed.
PMID- 27614930
TI - [Satisfaction according to health care insurance systems in an emergency
department].
AB - INTRODUCTION: Health satisfaction is a fundamental measure of the quality of
health services. This study aims to validate and analyse the results of a quality
of care questionnaire to assess the level of satisfaction of patients attended in
the emergency department of a high complexity hospital. METHODS: Observational,
cross-sectional study, with a questionnaire designed to assess the quality of
service and satisfaction at the end of care in the emergency department.
Descriptive statistics of scale were established and presented, as well as
determining the construct validity, overall reliability, internal and concurrent
validity of an overall against a uni-dimensional scale. RESULTS: A total of 5,961
records were reviewed, most of them (77.3%) reported by patients in the Mandatory
Health Plan. High levels of satisfaction overall and by subgroups were found.
There were no significant differences between subgroups, with 86.8 for those with
Pre-paid Medical Care Plan and 84.4 for mandatory health plan. Cronbach's alpha
for the questionnaire was 0.90. CONCLUSIONS: The questionnaire proved to be
reliable and valid in determining the quality and satisfaction with care. The
results showed high levels of satisfaction overall and in the domains. A low
consistency between the results of the multidimensional and unidimensional
satisfaction scales suggests that there were aspects of satisfaction not
investigated on the multidimensional scale. Ecologically-designed before and
after studies are required to evaluate the effectiveness of interventions in
satisfaction.
PMID- 27614931
TI - Narcotics and Sedative Use in Preterm Neonates.
AB - OBJECTIVES: To evaluate patterns of narcotic and sedative use in neonatal
intensive care units (NICUs) across Canada using data collected by the Canadian
Neonatal Network. STUDY DESIGN: We conducted a retrospective observational cohort
study of preterm neonates at <33 weeks' gestation and admitted to a participating
Canadian Neonatal Network NICU. The proportion of all neonates who received
sedative(s), narcotic(s), or either sedative(s), narcotic(s), or both during
their NICU stay was calculated for each year. Because opioids are used for
premedication before intubation, only continuous infusions of a narcotic drug
were included. Variation in narcotics and sedative usage between sites in 2014
was determined using logistic regression analysis, with adjustment for
gestational age, surgery, and mechanical ventilation. RESULTS: Of 20 744
neonates, 29% of neonates received a narcotic, a sedative, or both; 23% received
a narcotic and 17% a sedative. Although no clinically significant changes in drug
exposure were documented during the 5-year period, there were statistically
significant differences in narcotic and sedative use between sites, ranging from
3% to 41% for narcotic and 2% to 48% for sedative use (aORs 0.2-5.7 and 0.1-15,
respectively, P < .05). CONCLUSIONS: Exposure to narcotic or sedative agents is
highly variable in preterm neonates across Canada despite concerns of adverse
outcomes associated with these drugs. The tremendous variation in practice
suggests that further research on their current usage, as well as identifying
optimal practice procedures is warranted.
PMID- 27614933
TI - Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia
Ischemia in Male Rat Pups.
AB - Term asphyxiated newborns remain at risk of developing brain injury despite
available neuropreventive therapies such as hypothermia. Neurorestorative
treatments may be an alternative. This study investigated the effect of
sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term
equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal
day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8%
oxygen; sham-operated rat pups served as the control. Both groups were randomized
to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis
was performed on P27. At P30, the rats were sacrificed, and their brains were
extracted. The surfaces of both hemispheres were measured on hematoxylin and
eosin-stained brain sections. Mature neurons and endothelial cells were
quantified near the infarct boundary zone using immunohistochemistry. HI caused
significant gait impairment and a reduction in the size of the left hemisphere.
Treatment with sildenafil led to an improvement in the neurological deficits as
measured by gait analysis, as well as an improvement in the size of the left
hemisphere. Sildenafil, especially at higher doses, also caused a significant
increase in the number of neurons near the infarct boundary zone. In conclusion,
sildenafil administered after neonatal HI may improve brain injury recovery by
promoting neuronal populations.
PMID- 27614934
TI - Corrigendum to "Angiotensin(1-7) attenuated angiotensin II-induced hepatocyte EMT
by inhibiting NOX-derived H2O2-activated NLRP3 inflammasome/IL-1beta/Smad
circuit": [Free Radic. Biol. Med. 97(2016) 531-543].
PMID- 27614932
TI - Linking Frailty Instruments to the International Classification of Functioning,
Disability, and Health: A Systematic Review.
AB - To date, the major dilemma concerning frailty is the lack of a standardized
language regarding its operationalization. Considering the demographic challenge
that the world is facing, standardization of frailty identification is indeed the
first step in tackling the burdensome consequences of frailty. To demonstrate
this diversity in frailty assessment, the available frailty instruments have been
linked to the International Classification of Functioning, Disability, and Health
(ICF): a standardized and hierarchically coded language developed by World Health
Organization regarding health conditions and their positive (functioning) and
negative (disability) consequences. A systematic review on frailty instruments
was carried out in PubMed, Web of Knowledge, and PsycINFO. The items of the
identified frailty instruments were then linked to the ICF codes. 79 original or
adapted frailty instruments were identified and categorized into single (n = 25)
and multidomain (n = 54) groups. Only 5 frailty instruments (indexes) were linked
to all 5 ICF components. Whereas the ICF components Body Functions and Activities
and Participation were frequently linked to the frailty instruments, Body
Structures, Environmental and Personal factors were sparingly represented mainly
in the multidomain frailty instruments. This review highlights the heterogeneity
in frailty operationalization. Environmental and personal factors should be given
more thought in future frailty assessments. Being unambiguous, structured, and
neutral, the ICF language allows comparing observations made with different
frailty instruments. In conclusion, this systematic overview and ICF translation
can be a cornerstone for future standardization of frailty assessment.
PMID- 27614936
TI - Body Composition and Advanced Heart Failure Therapy: Weighing the Options and
Outcomes.
PMID- 27614935
TI - Prospective noninterventional study on peripheral blood stem cell mobilization in
patients with relapsed lymphomas.
AB - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to
rescue hematopoiesis is considered standard care for patients with a relapsed
chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for
poor mobilization in several studies. The aim of this prospective
noninterventional clinical audit was to review the mobilization strategies used
by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010
and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were
prospectively registered. Almost all patients were mobilized with chemotherapy
plus G-CSF (96%), but there was a large variation in chemotherapy schedules.
Thirty (11%) of them were poor mobilizers (<2 * 106 CD 34+ cells/kg body weight)
at the first mobilization. Poor mobilization was not associated with gender, age,
bone marrow involvement at diagnosis, primary diagnosis, number of previous
chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The
use of high dose cyclophosphamide alone was associated with mobilization failure
(P = 0.0006), whereas the use of a platinum-containing regimen was associated
with a good mobilization outcome (P = 0.013). Because failure rate is low, we can
conclude from this study that PBSC mobilization failure in relapsed lymphomas is
not an important problem in the EBMT centers.
PMID- 27614937
TI - Circulating Galectin-3 Levels Are Persistently Elevated After Heart
Transplantation and Are Associated With Renal Dysfunction.
AB - OBJECTIVES: This study evaluated changes in serum levels of galectin (Gal)-3
before and after heart transplantation (HTx) and assessed the role of pre-HTx Gal
3 as a biomarker for post-HTx outcomes. BACKGROUND: Gal-3 is a novel biomarker
that reflects cardiac remodeling and fibrosis. Elevated serum Gal-3 levels are
associated with poor prognosis in heart failure patients. Whether Gal-3 levels
change following HTx and the significance of post-HTx outcomes are unknown.
METHODS: Serum Gal-3 levels were measured in 62 patients at 118 days
(Interquartile Range [IQR]: 23 to 798 days) before and 365 days (IQR: 54 to 767
days) post HTx. Cardiac tissue taken during routine post-HTx endomyocardial
biopsy was evaluated to assess the correlation between tissue Gal-3 staining and
serum Gal-3 levels and with the presence of myocardial hypertrophy and fibrosis.
RESULTS: Serum Gal-3 levels remained significantly elevated (>17.8 ng/ml) in 35
patients (56%) post HTx. There was a significant inverse correlation between Gal
3 levels and glomerular filtration rate measured before and after HTx (p >
0.005). There was no association between Gal-3 serum level and Gal-3 staining of
myocardial tissue or with the presence of myocyte hypertrophy and interstitial
fibrosis post HTx. Elevated pre-HTx Gal-3 levels were associated with reduced
post-HTx exercise capacity, but this association was not significant after
adjustment for age, body mass index, and glomerular filtration rate. CONCLUSIONS:
This is the first study to demonstrate the fact that Gal-3 levels remain elevated
in the majority of patients despite HTx and is associated with renal dysfunction.
Our findings suggest Gal-3 is a systemic rather than cardiac-specific biomarker.
PMID- 27614938
TI - Angiotensin Receptor-Neprilysin Inhibition in Heart Failure With Reduced Ejection
Fraction: A Paradigm for All?
PMID- 27614939
TI - The HeartMate Risk Score Identifies Patients With Similar Mortality Risk Across
All INTERMACS Profiles in a Large Multicenter Analysis.
AB - OBJECTIVES: This study sought to assess the performance of the HeartMate Risk
Score (HMRS) in a large multicenter cohort, with a focus on its performance as a
function of disease severity. BACKGROUND: The HMRS has been proposed as a simple
tool for risk stratification of LVAD recipients, but subsequent studies have
challenged its validity. METHODS: We performed a retrospective, longitudinal,
comparative study using the INTERMACS (Interagency Registry for Mechanically
Assisted Circulatory Support) database. The HMRS was calculated for each patient
and its association with mortality was assessed using Cox models, including a pre
specified interaction by INTERMACS profile groups (1 vs. 2 vs. 3 vs 4+). RESULTS:
Among 10,847 patients with a mean age of 57.0 +/- 12.9 years, 78.9 % were male;
and 14.1%, 37.4%, 30.4%, and 18.2% were in INTERMACS profile groups 1, 2, 3, and
>=4, respectively. The HMRS showed moderate discrimination for both short-term
(90-day, C-index 0.62) and long-term (2-years, C-index 0.60) mortality, with no
significant difference between axial and centrifugal devices. Patients in the
highest HMRS group had a relative risk of 90-day mortality 2.8 times greater than
those in the lowest HMRS group (13.0% vs. 4.7%; p < 0.001). Importantly, the
relative risks of higher HMRS scores were similar across INTERMACS profile
groups, with subgroups of patients in INTERMACS profile 1 and 2 having comparable
or lower mortality than some in INTERMACS profile 4+. CONCLUSIONS: The HMRS is a
valid means of risk-stratifying patients across all INTERMACS profiles and may be
superior to traditional INTERMACS classification. Risk stratification with the
HMRS showed that patients within each INTERMACS profile groups have a wide
spectrum of mortality risk and low INTERMACS profiles should therefore not be
considered a contraindication to mechanical support.
PMID- 27614940
TI - Efficacy and Safety of Novel Oral Anticoagulants in Patients With Atrial
Fibrillation and Heart Failure: A Meta-Analysis.
AB - OBJECTIVES: This study investigated the efficacy and safety of novel oral
anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart
failure (HF) by a meta-analysis. BACKGROUND: AF is quite prevalent in patients
with HF. METHODS: Four phase III clinical trials comparing NOACs to warfarin in
patients with AF were included. Each patient was defined as affected by HF
according to the criteria of the trial in which the patient was enrolled. Pre
specified outcomes were the composite of stroke/systemic embolism (SSE); major,
intracranial, and any bleeding; and cardiovascular (CV) and all-cause death.
RESULTS: A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and
28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin
(median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE
(relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68)
and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in
patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95%
CI: 0.81 to 0.91; p < 0.01) and intracranial (RR: 0.74 95% CI: 0.63 to 0.88; p <
0.01) bleeding but increased rates of all-cause (RR: 1.70 95% CI: 1.31 to 2.19; p
< 0.01) and CV death (RR: 2.05 95% CI: 1.66 to 2.55; p < 0.01). NOACs, compared
with warfarin significantly reduced SSE and major, intracranial, and any
bleeding, regardless of the presence or absence of HF (pinteraction > 0.05 for
each). CONCLUSIONS: Patients with AF and HF had increased mortality but reduced
rates of intracranial and any bleeding compared with the no-HF patients, with no
differences in rates of SSE and major bleeding. NOACs significantly reduced SSE,
major bleeding, and intracranial hemorrhage in HF patients. No interactions in
efficacy and safety of NOACs were observed between AF patients with and without
HF.
PMID- 27614941
TI - Outcomes With Left Bundle Branch Block and Mildly to Moderately Reduced Left
Ventricular Function.
AB - OBJECTIVES: This study aimed to define the prognosis for patients with left
bundle branch block (LBBB) and a mildly to moderately reduced left ventricular
ejection fraction (LVEF) (36% to 50%) as well as to clarify whether LBBB remained
a negative prognostic marker in this group. BACKGROUND: LBBB is associated with
worse outcomes in patients with heart failure in the setting of severely reduced
LVEF. The level of morbidity and mortality associated with LBBB in the setting of
a mildly to moderately reduced LVEF (36% to 50%) has not been clearly
characterized. This knowledge is important to clarify the potential benefit of
cardiac resynchronization therapy in this group. METHODS: All patients identified
as having an LBBB from 1994 to 2014 were included in the study if they had a
baseline echocardiogram within 1 year and an LVEF between 36% and 50%. A control
group without intraventricular conduction abnormality matched on age, sex,
baseline LVEF, and date of echocardiogram was created. Outcomes were compared
between the 2 groups. RESULTS: Of 1,436 patients meeting inclusion criteria, 54%
were male. Mean age was 67 +/- 13 years, and mean LVEF at baseline was 44 +/- 4%.
There was no difference in baseline heart failure diagnosis between groups. There
were significantly higher rates of baseline coronary artery disease in the
control group and higher rates of aortic stenosis in the LBBB group. LBBB was
associated with significantly worse mortality (hazard ratio [HR]: 1.17; 95%
confidence interval [CI]: 1.00 to 1.36), an LVEF drop to 35% or less (HR: 1.34;
95% CI: 1.09 to 1.63), and the need for an implantable cardioverter-defibrillator
(HR: 1.50; 95% CI: 1.10 to 2.10). Mortality remained significantly higher in the
LBBB group when controlled for heart failure, coronary artery disease, and aortic
stenosis (p = 0.04). CONCLUSIONS: Patients with a mildly to moderately reduced
LVEF and LBBB have poor clinical outcomes that are significantly worse than those
for patients without conduction system disease. This group may obtain benefit
from cardiac resynchronization therapy and deserves to be studied in prospective
trials.
PMID- 27614943
TI - Centering the Patient in Meaningful Outcomes and Regulatory Approval.
PMID- 27614942
TI - The Impact of Obesity on Patients Bridged to Transplantation With Continuous-Flow
Left Ventricular Assist Devices.
AB - OBJECTIVES: This study sought to determine if obese patients had worse post-left
ventricular assist device (LVAD) implantation outcomes and if the implantation of
an LVAD allowed for weight loss. BACKGROUND: Obesity is a risk factor for
cardiovascular disease including heart failure. Obese heart failure patients have
better outcomes than those with normal weight; however, obese patients have worse
outcomes after heart transplantation. METHODS: Patients were identified in the
United Network for Organ Sharing (UNOS) database that underwent LVAD implantation
as bridge to transplantation from May 2004 and April 2014, with follow-up through
June 2014. Patients were grouped according to body mass index (BMI) based on the
World Health Organization classification. RESULTS: Among 3,856 patients, the risk
of death or delisting was not significantly different between BMI groups (p =
0.347). There was no increased risk of death (p = 0.234) or delisting (p =
0.918). The risk of complication requiring UNOS status upgrade was increased for
those with class II obesity or greater (hazard ratio: 1.48; p = 0.004), driven by
increased infection and thromboembolism. Obese patients had worse post
transplantation outcomes. Weight loss substantial enough to decrease BMI group
was achieved by a small proportion of patients listed with class I obesity or
greater (9.6% to 15.5%). CONCLUSIONS: Patients with obesity had similar freedom
from death or delisting while on LVAD support. However, class II obese or greater
patients had an increased risk of complications requiring UNOS status upgrade
compared with those with normal BMI during LVAD support and decreased post
transplantation survival. Weight loss on device therapy was possible, but
uncommon. Careful consideration is needed when a bridge to weight loss strategy
is proposed.
PMID- 27614944
TI - Explaining the Mortality-Readmissions Paradox for Racial and Ethnic Minorities.
PMID- 27614945
TI - Traffic-related air pollution increased the risk of Parkinson's disease in
Taiwan: A nationwide study.
AB - BACKGROUND: Ambient air pollution has been associated with many health
conditions, but little is known about its effects on neurodegenerative diseases,
such as Parkinson's disease (PD). In this study, we investigated the influence of
ambient air pollution on PD in a nationwide population-based case-control study
in Taiwan. METHODS: We identified 11,117 incident PD patients between 2007 and
2009 from the Taiwanese National Health Insurance Research Database and selected
44,468 age- and gender-matched population controls from the longitudinal health
insurance database. The average ambient pollutant exposure concentrations from
1998 through the onset of PD were estimated using quantile-based Bayesian Maximum
Entropy models. Basing from logistic regression models, we estimated the odds
ratios (ORs) and 95% confidence intervals (CIs) of ambient pollutant exposures
and PD risk. RESULTS: We observed positive associations between NOx, CO
exposures, and PD. In multi-pollutant models, for NOx and CO above the 75th
percentile exposure compared with the lowest percentile, the ORs of PD were 1.37
(95% CI=1.23-1.52) and 1.17 (95% CI=1.07-1.27), respectively. CONCLUSIONS: This
study suggests that ambient air pollution exposure, especially from traffic
related pollutants such as NOx and CO, increases PD risk in the Taiwanese
population.
PMID- 27614947
TI - Enhanced expression of immediate-early genes in mouse hippocampus after
trimethyltin treatment.
AB - Immediate-early genes (IEGs) are transiently and rapidly activated in response to
various cellular stimuli. IEGs mediate diverse functions during pathophysiologic
events by regulating cellular signal transduction. We investigated the temporal
expression of several IEGs, including c-fos, early growth response protein-1 (Egr
1), and activity-regulated cytoskeleton-associated protein (Arc), in trimethyltin
(TMT)-induced hippocampal neurodegeneration. Mice (7 weeks old, C57BL/6)
administered TMT (2.6mg/kg intraperitoneally) presented severe neurodegenerative
lesions in the dentate gyrus (DG) and showed behavioral seizure activity on days
1-4 post-treatment, after which the lesions and behavior recovered spontaneously
over time. c-fos, Egr-1, and Arc mRNA and protein levels significantly increased
in the mouse hippocampus after TMT treatment. Immunohistochemical analysis showed
that nuclear c-fos expression increased mainly in the DG, whereas nuclear Egr-1
expression was increased extensively in cornu ammonis (CA) 1, CA3, and the DG
after TMT treatment. Increased Arc levels were detected in the cellular
somata/dendrites of the hippocampal subregions after TMT treatment. Therefore, we
suggest that increased IEGs are associated with TMT-induced pathological events
in mouse hippocampus.
PMID- 27614946
TI - Electrocardiographic indicators of acute coronary syndrome are more common in
patients with ambulance transport compared to those who self-transport to the
emergency department journal of electrocardiology.
AB - INTRODUCTION: The American Heart Association recommends individuals with symptoms
suggestive of acute coronary syndrome (ACS) activate the Emergency Medical
Services' (EMS) 911 system for ambulance transport to the emergency department
(ED), which enables treatment to begin prior to hospital arrival. Despite this
recommendation, the majority of patients with symptoms suspicious of ACS continue
to self-transport to the ED. The IMMEDIATE AIM study was a prospective study that
enrolled individuals who presented to the ED with ischemic symptoms. OBJECTIVES:
The purpose of this secondary analysis was to determine differences in patients
presenting the ED for possible ACS who arrive by ambulance versus self-transport
on: 1) time-to-initial hospital electrocardiogram (ECG), 2) presence of ischemic
ECG changes, and 3) patient characteristics. METHODS: Initial 12-lead ECGs
acquired upon patient arrival to the ED were evaluated for ST-elevation, ST
depression, and T-wave inversion. ECG signs of ischemia were analyzed both
individually and collapsed into an independent dichotomous variable (ED ECG
ischemia yes/no) for statistical analysis. Patient characteristics tested
included: gender, age, race, ethnicity, English speaking, living alone, mode of
transport, and presenting symptoms (chest pain, jaw pain, shortness of breath,
nausea/vomiting, syncope, and clinical history). RESULTS: In 1299 patients (mean
age 63.9, 46.7% male), 384 (29.6%) patients arrived by ambulance to the ED. The
mean time-to-initial ECG was 47minutes for ambulance patients versus 53minutes
for self-transport patients (p<0.001). Mode of transport was found to be an
independent predictor for time-to-initial ECG controlling for age, gender, and
race (p=0.004). There were significantly higher rates of ECG changes of ischemia
for patients who arrived by ambulance versus self-transport (p=0.02), and patient
characteristics differed by mode of transport to the ED. DISCUSSION: Our findings
indicate that less than 30% of individuals with symptoms of ACS activate the EMS
'911' system for ambulance transport to the ED. Individuals more likely to
activate 911 have timelier ECG but higher rates of ischemic changes, specifically
ST-depression and T-wave inversion. Individuals least likely to activate 911 are
women, younger individuals, Latino ethnicity, live with a significant other, and
those experiencing chest or jaw pain.
PMID- 27614949
TI - Sleep related eating disorder: Importance of prebariatric evaluation-A case
report.
AB - Sleep-related eating disorder (SRED) is a parasomnia characterised by recurrent
episodes of eating after arousal from sleep, occurring in an unconscious and
involuntary manner. It has been reported mainly in association with the use of
psychotropic medications. This case report is of a patient diagnosed with a sleep
related eating disorder associated with amnesia in the postoperative period
following bariatric surgery. Such eating episodes without awareness in
postoperative period might have devastating results by disturbing compliance with
suggested eating behaviours. Although it is a rare condition, SRED should be
screened for among bariatric surgery candidates, and those affected should be
directed for the appropriate treatment. Also whether SRED should be considered a
contraindications to bariatric should be considered.
PMID- 27614948
TI - The experimental analysis of the interruptive, interfering, and identity
distorting effects of chronic pain.
AB - Pain is an unpleasant sensory and emotional experience urging the individual to
take action to restore the integrity of the body. The transition from a common
episode of acute pain to a state of intermittent or chronic pain has been a
constant preoccupation of researchers and clinicians alike. In this review, we
approach chronic pain from a modern learning perspective that incorporates
cognitive, affective, behavioral and motivational aspects. We view pain as a
biologically hard-wired signal of bodily harm that competes with other demands in
the person's environment. The basic tenet is that pain urges people to interrupt
ongoing activity, elicits protective responses that paradoxically increase
interference with daily activities, and compromises the sense of self. Here we
briefly summarize existing evidence showing how pain captures attention, and how
attention for pain can be controlled. We also consider pain as a strong motivator
for learning, and review the recent evidence on the acquisition and
generalization of pain-related fear and avoidance behavior, which are likely to
interfere with daily life activities. We highlight the paradoxical effects of
pain avoidance behavior, and review treatment effects of exposure in vivo. A
generally neglected area of research is the detrimental consequences of repeated
interference by pain with daily activities on one's sense of "self". We end this
review with a plea for the implementation of single-case experimental designs as
a means to help customize and develop novel cognitive-behavioral treatments for
individuals for chronic pain aimed at reducing the suffering of this large group
of individuals.
PMID- 27614950
TI - Associations between behavioural risk factors and overweight and obesity among
adults in population-based samples from 31 countries.
AB - OBJECTIVE: Concern about overweight and obesity is growing worldwide, and more
research to examine behaviours associated with the risk for increased weight in
adult populations is needed. The aim of this study was to estimate associations
between behavioural risk factors and overweight and obesity among adults in
nationally representative population samples from 20 countries in Europe, 8
countries in Asia, Australia, Chile and USA. METHODS: This secondary analysis is
based on the International Social Survey Program (ISSP), 2011-2013, Health and
Health Care Module. In a cross-sectional population-based survey (N=48,741) (mean
age 46.6 years, SD=17.4, age range 15-102 years) simple or multi-stage stratified
random sampling was used, yielding representative samples of the adult population
of respective countries. Body Mass Index was assessed by self-reported height and
weight. Correlates were risk behaviours for chronic disease (smoking status,
alcohol intake, consumption of fruits and vegetable (=FV), and physical
activity). RESULTS: Overall, for all 31 countries the prevalence of overweight or
obesity was 44.1%, 31.7% overweight and 12.4% obese. In adjusted logistic
regression models, among men and among women ex-smoking was positively associated
with both overweight and obesity, while light or moderate smoking overall and
among men were inversely related with obesity. Moderate alcohol use was
positively associated with both overweight and obesity, while heavy alcohol use
was negatively associated with overweight. The daily consumption of FV was found
to be protective from both overweight and obesity, overall and for men but not
for women. Physical activity was positively associated with overweight but not
obesity. CONCLUSIONS: Some risk behaviours for chronic disease appear to be
associated with overweight and obesity among adults. Interventions targeting
these risk behaviours may have the potential to reduce weight.
PMID- 27614951
TI - Evaluation of the rotational alignment of the tibial component in total knee
arthroplasty: position prioritizing maximum coverage.
AB - BACKGROUND: The standard for rotational alignment of the tibial component in
total knee arthroplasty (TKA) remains unclear. Cases often require positioning of
the tibial component, prioritizing adequate coverage of resected bone surface
rather than alignment with the tibial rotational axis. We investigated tibial
component position in TKA, prioritizing maximum coverage of resected bone
surface, and evaluated the correlation with the tibial anteroposterior (AP) axis.
METHODS: We analyzed preoperative computed tomography images for primary TKA in
106 cases and 157 knees, using three-dimensional planning software. Tibial
component position prioritizing maximum coverage of resected bone surface was
simulated, and results were compared with the AP axis. Rotational alignment angle
was defined as that between a line perpendicular to the tibial AP axis and a line
connecting the posterior edge of the tibial component. RESULTS: The simulated
tibial component was more externally rotated by a mean 4.5 degrees +/- 4.2
degrees . The alignment angle showed normal distribution, but variability was
large, ranging from 5.1 degrees internal rotation to 16.2 degrees external
rotation. In 138 of 157 (87.9 %) knees, the tibial component was positioned in
the externally rotated position with respect to the AP axis. The tibial component
was aligned within the medial one-third of the patellar tendon in 122 of 157
(77.7 %) knees. CONCLUSIONS: The tibial component aligned using coverage
prioritizing was externally rotated, although large variability was observed.
Rotational alignment was optimal in 79 % of cases when the tibial component was
aligned with coverage prioritizing, but hyperexternal rotation was observed in
patients with severe knee deformation.
PMID- 27614952
TI - Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11
Polymorphisms.
AB - OBJECTIVE: Since gastric cancer (GC) cells exhibited higher grades of SHP-2
encoded by PTPN11 than normal cells, it would be intriguing to explore whether
PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy
effectiveness and GC prognosis among a Chinese population. METHODS: Altogether
430 late-stage GC patients and 960 healthy controls matched with age and sex were
incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were
genotyped by polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4
cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
using the logistic regression. Survival curves were plotted with Kaplan-Meier
method and the COX proportional hazard model was used to analyze independent
factors for GC prognosis. RESULTS: For rs12229892, AA and GA genotypes would
cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60;
95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly
associated with a decrease in the risk of GC when compared with G allele (OR =
0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle
chemotherapy suggested that chemotherapy was significantly more effective for GA
and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides,
the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking,
family history, intake of processed food and H .pylori infection) on GC risk was
considered as positive interaction, while that of rs2301756 (AA) and the above
parameters was deemed as negative interaction. Finally, differentiation degree,
axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent
risk factors for GC development (all P < 0.05). CONCLUSION: Since rs2301756
polymorphism of PTPN11 was associated with reduced risk of GC and better effects
of chemotherapy on GC, it can be considered as a predictor of GC prognosis and
the treatment target for GC.
PMID- 27614953
TI - Epidemiology and Early Detection of Cervical Cancer.
AB - The new German S3 guideline 'Prevention of Cervical Cancer' published in 2016 is
based on the latest available evidence about cervical cancer screening and
treatment of cervical precancer. Large randomized controlled trials indicate that
human papillomavirus (HPV)-based screening may provide better protection against
cervical cancer than cytology alone through improved detection of premalignant
disease in the first screening round prior to progression. Therefore, women aged
30 years and older should preferably be screened with HPV testing every 3-5 years
(cytology alone every 2 years is an acceptable alternative). Co-testing is not
recommended. Screening should start at 25 years using cytology alone every 2
years. The preferred triage test after a positive HPV screening test is cytology.
Women positive for HPV 16 and HPV 18 should receive immediate colposcopy. Another
alternative triage method is p16/Ki-67 dual stain cytology. The mean yearly
participation rate in Germany is between 45 and 50%. Offering devices for HPV
self-sampling has the potential to increase participation rates in those women
who are at higher risk of developing cervical cancer. Regarding primary
prevention, the 9-valent vaccine may provide protection against up to 85% of
cervical intraepithelial neoplasia (CIN) 3 and 90% of cervical cancer, and is
available in Europe as a 2-dose schedule from May 2016.
PMID- 27614954
TI - Association of Adolescent Dimensional Borderline Personality Pathology with Past
and Current Nonsuicidal Self-Injury and Lifetime Suicidal Behavior: A Clinical
Multicenter Study.
AB - Descriptive diagnoses of nonsuicidal self-injury (NSSI) and suicide attempts
(SAs) may detract from underlying dimensional borderline personality pathology (D
BPP). This study aimed to investigate D-BPP in adolescent inpatients with NSSI
and SAs. A consecutive sample of 359 adolescent inpatients was assessed for
current and past NSSI and life-time SAs. D-BPP and current mental health problems
were measured using the Dimensional Assessment of Personality Pathology and the
Strengths and Difficulties Questionnaire, respectively. D-BPP was significantly
associated with both current (p < 0.001) and past NSSI (p = 0.025) and life-time
SAs (p < 0.001) compared to their non-self-harming peers. Patients with current
and past NSSI did not differ in terms of D-BPP or current mental health problems.
A multivariate model did not show any additional influence of current mental
health problems over and above D-BPP in predicting NSSI and SAs. It can be
hypothesized that D-BPP underlies adolescent self-harm and may persist even after
its termination, promoting a higher burden of mental health problems.
PMID- 27614955
TI - Differential Progression of Midbrain Atrophy in Parkinsonism: Longitudinal MRI
Study.
AB - AIMS: To elucidate different patterns of progression of midbrain atrophy in
patients with Richardson's syndrome (RS), progressive supranuclear palsy
parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance
imaging (MRI)-based visual rating indexes. METHODS: We recruited 12 patients with
PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at
least 2 years (mean +/- SD, 4.9 +/- 1.6 years) after the initial MRI. MRI-based
visual rating indexes were used to estimate midbrain atrophy, including the ratio
of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image,
the length between the interpeduncular fossa and the center of the cerebral
aqueduct at the midmammillary-body level (MTEGM) on axial images, and the morning
glory sign. RESULTS: Initially, there were no differences in MRI-based visual
rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and
lower MTEGM compared with PSP-P and PD. In PD, the P/M ratio and MTEGM remained
stable with disease progression. However, the extent of changes between initial
and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for
PD. Finally, PSP-P showed a higher P/M ratio and lower MTEGM compared with PD in
the follow-up, while PSP-RS still exhibited the most profound changes.
CONCLUSIONS: Midbrain atrophy progresses differentially in patients with PSP-RS,
PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based
visual rating indexes can help distinguish patients with PSP-P from those with
PSP-RS and PD.
PMID- 27614956
TI - Ongoing Clinical Trials in Testicular Cancer: The TIGER Trial.
PMID- 27614957
TI - Mapping marine debris across coastal communities in Belize: developing a baseline
for understanding the distribution of litter on beaches using geographic
information systems.
AB - Monitoring of marine debris (also known as marine litter) is an essential step in
the process to eradicate ecological dangers in marine ecosystems caused by
humans. This study examines marine debris in the Caribbean country of Belize
using geographic information systems (GIS) to develop (1) a detailed data library
for use on handheld Global Positioning System (GPS) units and tablets with mobile
mapping applications for deployment in the field and (2) a freely available,
online mapping portal to share data with Belizeans to encourage future citizen
science efforts. Four diverse communities were targeted ranging from larger more
populated towns, to smaller villages across central and southern Belize: San
Pedro, Caye Caulker, Punta Gorda, and Monkey River. Fieldwork was conducted over
1 month, during which data points were collected in 50-m surveys followed by
debris cleanup and removal. Features in our database included material, quantity,
item, brand, and condition. Over 6000 pieces of debris were recorded in GIS for
further analysis, and 299 gal of debris were removed from the shores of Belize.
The most abundant form of debris observed was plastic (commonly bottles) across
all locations; plastic comprised 77.6 % of all debris items observed. Through
GIS, a detailed snapshot understanding of debris patterns across multiple
settings in Belize was documented. Ongoing collaborations with local
organizations in Belize have demonstrated significant interest and utility for
such GIS approaches in analyzing and managing marine debris. The data,
methodology, visual representations, and online mapping platform resulting from
this research are a first step in directly supporting local Belizean community
advocacy and policy, while contributing to larger institutional strategies for
addressing marine debris issues in the Caribbean.
PMID- 27614958
TI - Analysis of visible and near infrared spectral reflectance for assessing metals
in soil.
AB - Visible and near infrared reflectance (VNIR; 350-2500 nm) spectroscopy has
greatly been used in soils, especially for studying variability in spectrally
active soil components (e.g., organic carbon, clays, and Fe/Al oxides) based on
their diagnostic spectral features. In recent years, this technique has also been
applied to assess soil metallic ions. In this research, the feasibility of VNIR
spectroscopy for determination of soil metals was investigated with two soil data
sets: (i) artificially metal-spiked and (ii) in situ metal-contaminated soils.
Results showed that reflectance spectra of neither metal-spiked soils with Cd,
As, and Pb even at their higher concentrations of 20, 900, and 1200 mg kg(-1),
respectively, nor in situ metal-contaminated soils (with concentrations of 30 mg
Cd, 3019 mg As, and 5725 mg Pb kg(-1) soil) showed any recognized absorption
peaks that correspond to soil metal concentrations. We observed variations in
reflectance intensity for in situ metal-contaminated soils only, showing higher
reflectance across the entire spectrum for strongly and lower for less metal
contaminated soils. A significant correlation was found between surface soil
metals' concentrations and continuum removed spectra, while soil metals were also
found significantly associated with soil organic matter and total Fe. A partial
least square regression with cross-validation approach produced an acceptable
prediction of metals (R (2) = 0.58-0.94) for both soil data sets, metal-spiked
and in situ metal-contaminated soils. However, high values of root mean square
error ruled out practical application of the achieved prediction models.
PMID- 27614959
TI - Copepod carcasses in a tropical estuary during different hydrographical settings.
AB - Dead copepods (carcasses) are widespread in aquatic systems, but their scientific
quantification is rare due to the difficulty in discriminating them from live
ones. In this paper, we hypothesized that due to large spatial and temporal
changes in hydrography in the Cochin backwaters, the percentage of copepod
carcasses in the system could also change significantly on a spatial and temporal
scale. In order to understand this aspect, we quantified the live and dead
copepods in the Cochin backwaters under different hydrographical settings based
on live and mortal staining technique. The most prominent temporal hydrographical
feature during the study period was the large decline in salinity across the
system, which was more pronounced downstream (15-20 units) and was caused by the
large freshwater influx associated with the southwest monsoon. During the entire
sampling period, copepod carcasses were pervasive all over the study area with
large spatial and temporal variations in their percentage contribution (2.5-35.8
%) to the total community abundance. During all sampling, carcasses concentrated
more in the downstream region, with maximum turbidity (16.5-35.8 %), than in the
upstream region (2.5-14.5 %). The percentage of carcasses was the highest during
the onset of the southwest monsoon (av. 23.64 +/- 8.09 %), followed by the pre
southwest monsoon (av. 13.59 +/- 6.72 %) and southwest monsoon (av. 8.75 +/- 4.14
%). During the onset of the southwest monsoon, copepod carcasses in the
downstream were contributed by ~80 % high saline and ~15 % low saline species,
indicating a salinity shock-induced mortality. On the other hand, the cumulative
effect of the long residence time of the Cochin backwaters and high partial
predation rate of carnivores contributed to the high abundance of carcasses
during the pre-monsoon.
PMID- 27614960
TI - Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective
effects of exogenous melatonin.
AB - In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master
clock and by generation of temporal oscillations regulates the peripheral organs
acting as autonomous clocks resulting in overt behavioral and physiological
rhythms. SCN also controls synthesis and release of melatonin (hormonal message
for darkness) from pineal. Nitric Oxide (NO) acts as an important
neurotransmitter in generating the phase shifts of circadian rhythms and
participates in sleep-wake processes, maintenance of vascular tone as well as
signalling and regulating inflammatory processes. Aging is associated with
disruption of circadian timing system and decline in endogenous melatonin leading
to several physiological disorders. Here we report the effect of aging on NO
daily rhythms in various peripheral clocks such as kidney, intestine, liver,
heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12
and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in
alteration of NO levels as well as phase of NO in both 12 and 24 months groups.
Correlation analysis demonstrated loss of stoichiometric interaction between the
various peripheral clocks with aging. Age induced alterations in NO daily rhythms
were found to be most significant in liver and, interestingly least in lungs.
Neurohormone melatonin, an endogenous synchroniser and an antiaging agent
decreases with aging. We report further differential restoration with exogenous
melatonin administration of age induced alterations in NO daily rhythms and mean
levels in kidney, intestine and liver and the stoichiometric interactions between
the various peripheral clocks.
PMID- 27614963
TI - Retraction Note to: Evaluation of pharmaceutical care in a diabetes ward from
China: a pre- and post-intervention study.
PMID- 27614961
TI - Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation.
AB - INTRODUCTION: The physiologic vitamin D (VD), 1alpha,25(OH)2D3 (1,25D) is a local
paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar
type II cell and lipofibroblast proliferation and differentiation, parenterally
administered 1,25D has been shown to enhance neonatal lung maturation; but due to
the potential systemic side effects of the parenteral route, the translational
value of these findings might be limited. To minimize the possibility of systemic
toxicity, we examined the effects of VD on neonatal lung maturation, when
delivered directly to lungs via nebulization. METHODS: One-day-old rat pups were
administered three different doses of 1,25D and its physiologic precursor 25(OH)D
(25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed
for lung, kidneys, and blood collection to determine markers of lung maturation,
and serum 25D and calcium levels. RESULTS: Compared to controls, nebulized 25D
and 1,25D enhanced lung maturation as evidenced by the increased expression of
markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARgamma,
C/EBPalpha), and endothelial (VEGF, FLK-1) differentiation, surfactant
phospholipid synthesis, and lung morphology without any significant increases in
serum 25D and calcium levels. CONCLUSIONS: Inhaled VD is a potentially safe and
effective novel strategy to enhance neonatal lung maturation.
PMID- 27614962
TI - Parental views on otitis media: systematic review of qualitative studies.
AB - This study aims to describe parental experiences and perspectives of caring for a
child with otitis media. We conducted a systematic review of qualitative studies
on parental perspectives on caring for a child with otitis media. We searched
electronic databases to July 2015. Seventeen studies involving 284 participants
from six countries were included. We identified seven themes: diminishing
competency (guilt over failure to identify symptoms, helpless and despairing,
fear of complications, disempowered and dismissed); disrupting life schedules
(disturbing sleep, interfering with work, burden on family); social isolation
(stigma and judgement, sick consciousness); threatening normal development
(delaying growth milestones, impairing interpersonal skills, impeding education);
taking ownership (recognising symptoms, diagnostic closure, working the system,
protecting against physical trauma, contingency planning); valuing support
(needing respite, depending on community, clinician validation); and cherishing
health (relief with treatment success, inspiring resilience). CONCLUSION: The
additional medical responsibilities and anxieties of parents caring for a child
with otitis media, often discounted by clinicians, can be disempowering and
disruptive. Chronicity can raise doubt about treatment efficacy and parental
competency, and fears regarding their child's development. Care that fosters
parental confidence and addresses their concerns about the child's development
may improve treatment outcomes for children with otitis media. WHAT IS KNOWN: *
Otitis media is a leading cause of conductive hearing loss in children. *
Parental perception of the treatment burden of otitis media can potentially
affect their confidence and ability to care for their child. What is New: * We
identified five themes to reflect parental perspectives: diminishing competency,
disrupting life schedules, social isolation, threatening normal development,
taking ownership, valuing support, and cherishing health. * Parents may perceive
caring for a child with otitis media as disempowering and disruptive and with
reoccurrence doubt treatment efficacy and their parental competency and develop
fears regarding their child's development.
PMID- 27614964
TI - Invagination of intra-abdominal structures in the lumbar intervertebral disc
space.
AB - Invagination of peritoneal or retroperitoneal structures into the intervertebral
disc space of the lumbar spine is extremely rare. In this article the imaging
features and clinical findings are demonstrated in four patients with
intervertebral invagination of intra-abdominal structures. Plain radiographs, CT
scans, and MR images showed disruption of the anterior ligamentous complex (ALC)
and invagination of various structures into the disc space, including the vena
cava, iliac vessels, intestine, the torn redundant anterior longitudinal
ligament, retroperitoneal fat, and the psoas muscle. The invaginations occurred
at the level of L3-L4 and L4-L5 in one case each and at L5-S1 in two cases.
Follow-up imaging in three cases (1, 5, and 8 years respectively) showed the
progression of the invagination. These cases demonstrate that a close evaluation
of this condition is necessary, particularly for older patients who show
disruption or laxity of the ALC, degenerative spondylosis with chronic segmental
instability, and osteoporosis of the lower lumbar spine.
PMID- 27614965
TI - Diagnostic accuracy of 3-T magnetic resonance imaging with 3D T1 VIBE versus
computer tomography in pars stress fracture of the lumbar spine.
AB - OBJECTIVE: To compare the diagnostic accuracy of 3-T magnetic resonance imaging
(MRI) with thin-slice 3D T1 VIBE sequence to 128-slice computer tomography (CT)
in pars stress fractures of the lumbar spine. MATERIALS AND METHODS: 3-T MRI and
CT of 24 patients involving 70 pars interarticularis were retrospectively
reviewed by four blinded radiologists. The fracture morphology (complete,
incomplete, or normal) was assessed on MRI and CT at different time points. Pars
interarticularis bone marrow edema (present or absent) was also evaluated on MRI.
RESULTS: In total, 14 complete fractures, 31 incomplete fractures and 25 normal
pars were detected by CT. Bone marrow edema was seen in seven of the complete and
25 of the incomplete fractures. The overall sensitivity, specificity and accuracy
of MRI in detecting fractures (complete and incomplete) were 97.7, 92.3, and 95.7
%, respectively. MRI was 100 % accurate in detecting complete fractures. For
incomplete fractures, the sensitivity, specificity, and accuracy of MRI were
96.7, 92.0, and 94.6 %, respectively. CONCLUSIONS: 3-T MRI with thin-slice 3D T1
VIBE is 100 % accurate in diagnosing complete pars fractures and has excellent
diagnostic ability in the detection and characterization of incomplete pars
stress fractures compared to CT. MRI has the added advantages of detecting bone
marrow edema and does not employ ionizing radiation.
PMID- 27614966
TI - Effects of Shenfu Injection () on cerebral metabolism in a porcine model of
cardiac arrest.
AB - OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on cerebral
metabolism in a porcine model of cardiac arrest (CA). METHODS: Thirty Wuzhishan
minipigs were randomly assigned to the control group (n=6), epinephrine group (EP
group, n=12) and Sfigroup (n=12). After 8 min of untreated ventricular
fifibrillation (VF), pigs in the EP group or Sfigroup were administered with
either EP (0.02 mg/kg) or Sfi(1.0 mL/kg), respectively. After successful
resuscitation, cerebrospinal fluid (CSF) levels of glucose, pyruvate, lactate,
glutamate and glycerol were measured at 1, 6, 12 and 24 h after recover from
spontaneous circulation (ROSC). In addition, neurologic defificit score (NDS) was
calculated at 24 h after ROSC. Surviving pigs were killed at 24 h after ROSC, and
the brain tissue was obtained for ultra-microstructure examination. RESULTS:
Compared with the EP group, CSF glucose and pyruvate levels were higher (all
P<0.01), and lactate levels were lower in the Sfigroup (P<0.01). Meanwhile, CSF
glutamate and glycerol levels in the Sfigroup were lower in comparison to the EP
group (all P<0.05). In addition, Sfidecreased NDS at 24 h after ROSC (P<0.01),
and alleviated the histopathological damage of the brain. CONCLUSIONS: Sficould
alleviate brain injury after CA, which may be associated with improving cerebral
metabolism.
PMID- 27614967
TI - Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid
accumulation in human L02 hepatocytes.
AB - OBJECTIVE: To investigate the effect of ginsenosides from stems and leaves of
ginseng on ethanol-induced lipid deposition in human L02 hepatocytes. METHODS:
L02 cells were exposed to ethanol for 36 h and treated with or without
ginsenosides. The viability of L02 cells was evaluated by methylthiazolyldiphenyl
tetrazolium bromide assay and the triglyceride (TG) content was detected. Lipid
droplets were determined by oil red O staining. Intracellular reactive oxygen
species (ROS) production and the mitochondrial membrane potential were tested by
flow cytometry. The ATP level was measured by reverse phase high performance
liquid chromatography. The expression of cytochrome p450 2E1 (CYP2E1) and
peroxisome proliferator-activated receptor alpha (PPARalpha) was detected by
reverse transcriptase-polymerase chain reaction and Western blotting,
respectively. RESULTS: Ethanol exposure resulted in the increase of TG level,
lipid accumulation and ROS generation, and the decrease of mitochondrial membrane
potential and ATP production in the cells. However, ginsenosides significantly
reduced TG content (9.69+/-0.22 MUg/mg protein vs. 4.93+/-0.49 MUg/mg protein,
P<0.01), and ROS formation (7254.8+/-385.7 vs. 5825.2+/-375.9, P<0.01).
Meanwhile, improvements in mitochondrial membrane potential (10655.33+/-331.34
vs. 11129.52+/-262.35, P<0.05) and ATP level (1.20+/-0.18 nmol/mg protein vs.
2.53+/-0.25 nmol/mg protein, P<0.01) were observed by treatment with
ginsenosides. Furthermore, ginsenosides could down-regulate CYP2E1 expression
(P<0.01) and upregulate PPARalpha expression (P<0.01) in ethanol-treated cells.
CONCLUSIONS: Ginsenosides could prevent ethanol-induced hepatocyte steatosis in
vitro related to the inhibition of oxidative stress and the improvement of
mitochondrial function. In addition, the modulation of CYP2E1 and PPARalpha
expression may also play an important role in the protective effect of
ginsenosides against lipid accumulation.
PMID- 27614968
TI - Cuban Americans (CAs) and Type 2 Diabetes: An Integrative Review of the
Literature.
AB - Type 2 diabetes is associated with increased morbidity and mortality in Hispanics
but few studies have been done to differentiate diabetes effects in Hispanic
subgroups, such as Cuban Americans. The purpose of this review was to
characterize the studies conducted on Cuban Americans with type 2 diabetes with
the aim of updating knowledge related to physiologic factors, psychologic
factors, and diabetes selfmanagement. An extensive literature search located 18
studies that met the inclusion criteria for this review. Previous studies
provided consistent evidence demonstrating the influence of lifestyle, metabolic,
and psychosocial risk factors that lead to poorer outcomes for CAs. No
intervention studies were found examining the effect of treatment and education
on diabetes control. Future research is needed to determine how these factors
associated with diabetes can be used in lowering risks and improving health
outcomes for Cuban Americans.
PMID- 27614969
TI - The analysis of anxiety and mood in healthy late-reproductive-stage women with
regard to hormonal and genetic factors.
AB - The purpose of this study was to determine whether anxiety and mood disorders in
late-reproductive-stage women are related to the serotonin transporter and
monoamine oxidase A gene polymorphisms. Research instrument used in this study
were the State-Trait Anxiety Inventory and the UWIST Mood Adjective Checklist.
The 44-bp VNTR polymorphism in the 5-HTT (SLC 6A4) promoter region and the 30-bp
VNTR polymorphism in the MAO-A promoter region were analyzed. The study included
345 healthy Polish women in the late reproductive stage. The mean age of the
participants was 42.3 +/- 4.5 years. State anxiety was observed in 16.8 % of the
women and trait anxiety in 14.5 %. There were no statistically significant
differences in the mood and the mean levels of anxiety depending on the presence
of the polymorphisms analyzed in this study. Depressed mood is frequent among
healthy women in the late reproductive stage. Anxiety is definitely less common.
The study did not demonstrate the relationship between the 5-HTT and MAO-A gene
polymorphisms, and the severity of anxiety and mood disorders in healthy late
reproductive-stage women.
PMID- 27614971
TI - Roles of organic anion transporters (OATs) in renal proximal tubules and their
localization.
AB - Organic anions (OAs) are secreted in renal proximal tubules in two steps. In the
first step, OAs are transported from the blood through basolateral membranes into
proximal tubular cells. The prototypical substrate for renal organic anion
transport systems, para-aminohippurate (PAH), is transported across basolateral
membranes of proximal tubular cells via OAT1 (SLC22A6) and OAT3 (SLC22A8) against
an electrochemical gradient in exchange for intracellular dicarboxylates. In the
second step, OAs exit into urine through apical membranes of proximal tubules.
This step is thought to be performed by multidrug efflux transporters and a
voltage-driven organic anion transporter. However, the molecular nature and
precise functional properties of these efflux systems are largely unknown.
Recently, we characterized an orphan transporter known as human type I sodium
phosphate transporter 4, hNPT4 (SLC17A3), using the Xenopus oocyte expression
system. hNPT4 acts as a voltage-driven efflux transporter ("human OATv1") for
several OAs such as PAH, estrone sulfate, diuretic drugs, and urate. Here, we
describe a model for an OA secretory pathway in renal tubular cells in which OAs
exit cells and enter the tubular lumen via hOATv1 (hNPT4). Additionally, hOATv1
functions as a common renal secretory pathway for both urate and drugs,
indicating that hOATv1 may be a leak pathway for excess urate that is reabsorbed
via apical URAT1 to control the intracellular urate levels. Therefore, we propose
a molecular mechanism for the induction of hyperuricemia by diuretics: the
diuretics enter proximal tubular cells via basolateral OAT1 and/or OAT3 and may
then interfere with the NPT4-mediated apical urate efflux in the renal proximal
tubule.
PMID- 27614970
TI - BAP1 immunohistochemistry and p16 FISH results in combination provide higher
confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two
tests.
AB - Differentiation of malignant pleural mesothelioma (MPM) from benign mesothelial
proliferation remains problematic. Loss of nuclear staining of BRCA1-associated
protein 1 (BAP1; detected using immunohistochemistry (IHC)) and homozygous
deletion (HD) of p16 (detected using fluorescence in situ hybridization (FISH))
are useful for differentiation of MPM from reactive mesothelial hyperplasia
(RMH), but the correlation between BAP1 expression loss and p16 HD has not been
fully described. We performed BAP1 IHC and p16-specific FISH for 40 MPM and 20
RMH cases, and measured proportions of cells showing BAP1 expression and p16 HD
for each case. The diagnostic accuracy for MPM and the cut-off values of the two
methods were assessed using receiver operating characteristic (ROC) analysis.
BAP1 expression loss, p16 HD and coexistence of both were present in 27 (67.5 %),
27 (67.5 %) and 17 (42.5 %) MPM cases, respectively. Three MPM cases (7.5 %) and
all 20 RMH cases had neither BAP1 loss nor p16 HD. There was no correlation
between the results of the two methods. Their combination showed higher
sensitivity (92.5 %, 37/40) and estimated probability than BAP1 IHC and p16
specific FISH used alone. BAP1 IHC and p16-specific FISH have independent
diagnostic value, and have increased reliability when used in combination, for
MPM diagnosis.
PMID- 27614975
TI - Determination of endocrine-disrupting compounds in water samples by magnetic
nanoparticle-assisted dispersive liquid-liquid microextraction combined with gas
chromatography-tandem mass spectrometry.
AB - A rapid extraction procedure is presented for the determination of five endocrine
disrupting compounds, estrone, ethinylestradiol, bisphenol A, triclosan, and 2
ethylhexylsalicylate, in water samples. The analysis involves a two-step
extraction procedure that combines dispersive liquid-liquid microextraction
(DLLME) with dispersive micro-solid phase extraction (D-MU-SPE), using magnetic
nanoparticles, followed by in situ derivatization in the injection port of a gas
chromatograph coupled to triple quadrupole mass spectrometry. The use of uncoated
or oleate-coated Fe3O4 nanoparticles as sorbent in the extraction process was
evaluated and compared. The main parameters involved in the extraction process
were optimized applying experimental designs. Uncoated Fe3O4 nanoparticles were
selected in order to simplify and make more cost-effective the procedure. DLLME
was carried out at pH 3, during 2 min, followed by the addition of the
nanoparticles for D-MU-SPE employing 1 min in the extraction. Analysis of spiked
water samples of different sources gave satisfactory recovery results for all the
compounds with detection limits ranging from 7 to 180 ng l-1. Finally, the
procedure was applied in tap, well, and river water. Graphical abstract Diagram
of the extraction method using magnetic nanoparticles (MNPs).
PMID- 27614974
TI - GlycoPep MassList: software to generate massive inclusion lists for glycopeptide
analyses.
AB - Protein glycosylation drives many biological processes and serves as markers for
disease; therefore, the development of tools to study glycosylation is an
essential and growing area of research. Mass spectrometry can be used to identify
both the glycans of interest and the glycosylation sites to which those glycans
are attached, when proteins are proteolytically digested and their glycopeptides
are analyzed by a combination of high-resolution mass spectrometry (MS) and
tandem mass spectrometry (MS/MS) methods. One major challenge in these
experiments is collecting the requisite MS/MS data. The digested glycopeptides
are often present in complex mixtures and in low abundance, and the most commonly
used approach to collect MS/MS data on these species is data-dependent
acquisition (DDA), where only the most intense precursor ions trigger MS/MS. DDA
results in limited glycopeptide coverage. Semi-targeted data acquisition is an
alternative experimental approach that can alleviate this difficulty. However,
due to the massive heterogeneity of glycopeptides, it is not obvious how to
expediently generate inclusion lists for these types of analyses. To solve this
problem, we developed the software tool GlycoPep MassList, which can be used to
generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC
MS/MS) experiments. The utility of the software was tested by conducting
comparisons between semi-targeted and untargeted data-dependent analysis
experiments on a variety of proteins, including IgG, a protein whose
glycosylation must be characterized during its production as a biotherapeutic.
When the GlycoPep MassList software was used to generate inclusion lists for LC
MS/MS experiments, more unique glycopeptides were selected for fragmentation.
Generally, ~30 % more unique glycopeptides can be analyzed per protein, in the
simplest cases, with low background. In cases where background ions from proteins
or other interferents are high, usage of an inclusion list is even more
advantageous. The software is freely publically accessible. Graphical abstract
Software increases the number of glycopeptides that get selected for MS/MS
analysis.
PMID- 27614972
TI - Song in an Affiliative Context Relates to the Neural Expression of Dopamine- and
Neurotensin-Related Genes in Male European Starlings.
AB - Some animals, including songbirds, vocalize at high rates when alone or in large
groups. In songbirds, vocal behavior in these contexts is important for song
learning and group cohesion. It is not obviously targeted at any particular
individual and is described as 'undirected'. Studies suggest a role for dopamine
(DA) in undirected song. The neuropeptide neurotensin (NT) can enhance
dopaminergic signaling upon binding to the NT receptor 1 (NTR1) and is found in
regions where DA can influence song, including the ventral tegmental area (VTA),
septum, and the song control nucleus Area X. To begin to test the hypothesis that
NT and DA in these regions interact to influence undirected song, we used
quantitative real-time PCR to relate undirected singing to mRNA expression of NT,
NTR1, tyrosine hydroxylase (TH; a synthetic enzyme for DA) and D1 and D2
receptors in male European starlings. TH and NT expression in VTA, and NT and D1
expression in Area X, positively correlated with song. NT markers also correlated
positively with DA markers in VTA. Given the role of VTA projections to Area X in
song learning, these results suggest that interactions between NT and DA in these
regions may contribute to vocal learning. In septum, NTR1 expression positively
correlated with song and NT and DA markers were correlated, suggesting that NT in
this region may influence dopaminergic transmission to facilitate undirected
vocalizations. Overall, these findings implicate interactions between NT and DA
in affiliative communication.
PMID- 27614976
TI - Determination of novel brominated flame retardants and polybrominated diphenyl
ethers in serum using gas chromatography-mass spectrometry with two simplified
sample preparation procedures.
AB - Two simple and efficient pretreatment procedures have been developed for the
simultaneous extraction and cleanup of six novel brominated flame retardants
(NBFRs) and eight common polybrominated diphenyl ethers (PBDEs) in human serum.
The first sample pretreatment procedure was a quick, easy, cheap, effective,
rugged, and safe (QuEChERS)-based approach. An acetone/hexane mixture was
employed to isolate the lipid and analytes from the serum with a combination of
MgSO4 and NaCl, followed by a dispersive solid-phase extraction (d-SPE) step
using C18 particles as a sorbent. The second sample pretreatment procedure was
based on solid-phase extraction. The sample extraction and cleanup were conducted
directly on an Oasis HLB SPE column using 5 % aqueous isopropanol, concentrated
sulfuric acid, and 10 % aqueous methanol, followed by elution with
dichloromethane. The NBFRs and PBDEs were then detected using gas chromatography
negative chemical ionization mass spectrometry (GC-NCI MS). The methods were
assessed for repeatability, accuracy, selectivity, limits of detection (LODs),
and linearity. The results of spike recovery experiments in fetal bovine serum
showed that average recoveries ranged from 77.9 % to 128.8 % with relative
standard deviations (RSDs) from 0.73 % to 12.37 % for most of the analytes. The
LODs for the analytes in fetal bovine serum ranged from 0.3 to 50.8 pg/mL except
for decabromodiphenyl ethane. The proposed method was successfully applied to the
determination of the 14 brominated flame retardants in human serum. The two
pretreatment procedures described here are simple, accurate, and precise, and are
suitable for the routine analysis of human serum. Graphical Abstract Workflow of
a QuEChERS-based approach (top) and an SPE-based approach (bottom) for the
detection of PBDEs and NBFRs in serum.
PMID- 27614977
TI - Simultaneous determination of halogenated contaminants and polycyclic aromatic
hydrocarbons: a multi-analyte method applied to filter-feeding edible organisms.
AB - This study develops and validates a novel analytical approach for the
simultaneous determination of 127 polychlorinated biphenyls (PCBs), together with
6 polychlorinated naphthalenes (PCNs) and 16 polycyclic aromatic hydrocarbons
(PAHs). PCBs, PCNs, and PAHs were subjected to a unique pretreatment protocol and
were simultaneously determined in a single chromatographic run, using GC-MS, in
environmental marine samples of mussels and clams. The results of the validation
experiments, which were performed on the standard reference materials (NIST SRM
1974C - slurried matrix and NIST SRM 2977 - freeze-dried matrix), were in
accordance with the certified and the reference values. The repeatability of the
method for all target compounds, expressed as mean relative standard deviations,
ranged from 2.5 to 5.1 % for PCBs, from 3.9 to 5.5 % for PCNs, and from 8.6 to
17.9 % for PAHs; the first value of each pair refers to the freeze-dried matrix
and the second to the fresh one, for each of the classes of compounds examined.
The quantification limits were in the range of 0.2-6 pg for PCBs, 0.4-8 pg for
PCNs, and 0.2-15 pg for PAHs (on column). The method recoveries yielded good
results (62 +/- 19 % for the freeze-dried matrix and 60 +/- 14 % for the fresh
one) and were not significantly reduced by adopting a single analytical protocol
compared with the use of different group-specific analytical methods. No serious
interferences were encountered and good selectivity was achieved. These results
show that this method allows one to increase the laboratory sample throughput
while requiring a small amount of tissue and saving time. Graphical Abstract
Simultaneous determination of halogenated contaminants and polycyclic aromatic
hydrocarbons: a multianalyte method applied to filter-feeding edible organisms.
PMID- 27614978
TI - Metabolite profiling in Trigonella seeds via UPLC-MS and GC-MS analyzed using
multivariate data analyses.
AB - Trigonella foenum-graecum is a plant of considerable value for its nutritive
composition as well as medicinal effects. This study aims to examine Trigonella
seeds using a metabolome-based ultra-performance liquid chromatography-mass
spectrometry (UPLC-MS) in parallel to gas chromatography-mass spectrometry (GC
MS) coupled with multivariate data analyses. The metabolomic differences of seeds
derived from three Trigonella species, i.e., T. caerulea, T. corniculata, and T.
foenum-graecum, were assessed. Under specified conditions, we were able to
identify 93 metabolites including 5 peptides, 2 phenolic acids, 22 C/O-flavonoid
conjugates, 26 saponins, and 9 fatty acids using UPLC-MS. Several novel
dipeptides, saponins, and flavonoids were found in Trigonella herein for the
first time. Samples were classified via unsupervised principal component analysis
(PCA) followed by supervised orthogonal projection to latent structures
discriminant analysis (OPLS-DA). A distinct separation among the investigated
Trigonella species was revealed, with T. foenum-graecum samples found most
enriched in apigenin-C-glycosides, viz. vicenins 1/3 and 2, compared to the other
two species. In contrast to UPLC-MS, GC-MS was less efficient to classify
specimens, with differences among specimens mostly attributed to fatty acyl
esters. GC-MS analysis of Trigonella seed extracts led to the identification of
91 metabolites belonging mostly to fatty acyl esters, free fatty acids followed
by organic acids, sugars, and amino acids. This study presents the first report
on primary and secondary metabolite compositional differences among Trigonella
seeds via a metabolomics approach and reveals that, among the species examined,
the official T. foenum-graecum presents a better source of Trigonella secondary
bioactive metabolites.
PMID- 27614979
TI - Erratum to: Microscopic visualization of testosterone in mouse testis by use of
imaging mass spectrometry.
PMID- 27614980
TI - Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound
assisted dispersive liquid-liquid microextraction coupled with ultra-high
performance liquid chromatography with tandem mass spectrometry.
AB - A new analytical method was developed for simultaneous determination of 12
pharmaceuticals using ultrasound-assisted dispersive liquid-liquid
microextraction (DLLME) followed by ultra-high performance liquid chromatography
with tandem mass spectrometry (UHPLC-MS/MS). Six nonsteroidal anti-inflammatory
drugs (NSAIDs, ketoprofen, mefenamic acid, tolfenamic acid, naproxen, sulindac,
and piroxicam) and six antibiotics (tinidazole, cefuroxime axetil, ciprofloxacin,
sulfamethoxazole, sulfadiazine, and chloramphenicol) were extracted by ultrasound
assisted DLLME using dichloromethane (800 MUL) and methanol/acetonitrile (1:1,
v/v, 1200 MUL) as the extraction and dispersive solvents, respectively. The
factors affecting the extraction efficiency, such as the type and volume of
extraction and dispersive solvent, vortex and ultrasonic time, sample pH, and
ionic strength, were optimized. The ultrasound-assisted process was applied to
accelerate the formation of the fine cloudy solution by using a small volume of
dispersive solvent, which increased the extraction efficiency and reduced the
equilibrium time. Under the optimal conditions, the calibration curves showed
good linearity in the range of 0.04-20 ng mL-1 (ciprofloxacin and sulfadiazine),
0.2-100 ng mL-1 (ketoprofen, tinidazole, cefuroxime axetil, naproxen,
sulfamethoxazole, and sulindac), and 1-200 ng mL-1 (mefenamic acid, tolfenamic
acid, piroxicam, and chloramphenicol). The LODs and LOQs of the method were in
the range of 0.006-0.091 and 0.018-0.281 ng mL-1, respectively. The relative
recoveries of the target analytes were in the range from 76.77 to 99.97 % with
RSDs between 1.6 and 8.8 %. The developed method was successfully applied to the
extraction and analysis of 12 pharmaceuticals in five kinds of water samples
(drinking water, running water, river water, influent and effluent wastewater)
with satisfactory results. Graphical Abstract Twelve pharmaceuticals in water
samples analyted by UHPLC-MS/MS using ultrasound-assisted DLLME.
PMID- 27614981
TI - Application of LC-MS-based metabolomics method in differentiating septic
survivors from non-survivors.
AB - Septic shock is the most severe form of sepsis, which is still one of the leading
causes of death in the intensive care unit (ICU). Even though early prognosis and
diagnosis are known to be indispensable for reaching an optimistic outcome,
pathogenic complexities and the lack of specific treatment make it difficult to
predict the outcome individually. In the present study, serum samples from
surviving and non-surviving septic shock patients were drawn before clinical
intervention at admission. Metabolic profiles of all the samples were analyzed by
liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. One thousand
four hundred nineteen peaks in positive mode and 1878 peaks in negative mode were
retained with their relative standard deviation (RSD) below 30 %, in which 187
metabolites were initially identified by retention time and database in the light
of the exact molecular mass. Differences between samples from the survivors and
the non-survivors were investigated using multivariate and univariate analysis.
Finally, 43 significantly varied metabolites were found in the comparison between
survivors and non-survivors. Concretely, metabolites in the tricarboxylic acid
(TCA) cycle, amino acids, and several energy metabolism-related metabolites were
up-regulated in the non-survivors, whereas those in the urea cycle and fatty
acids were generally down-regulated. Metabolites such as lysine, alanine, and
methionine did not present significant changes in the comparison. Six metabolites
were further defined as primary discriminators differentiating the survivors from
the non-survivors at the early stage of septic shock. Our findings reveal that LC
MS-based metabolomics is a useful tool for studying septic shock. Graphical
abstract ?.
PMID- 27614983
TI - Early Bilateral Gonadoblastoma in a Young Child with Mosaicism for Turner
Syndrome and Trisomy 18 with Y Chromosome.
AB - Mosaic Turner syndrome (TSM) commonly occurs in the form of 45,X/46,XX and
45,X/46,X,i(X)(q10). Mosaicism for a Y chromosome, 45,X/46,XY, has been well
documented and is associated with increased risk of gonadoblastoma (GB). To date,
there are only six reported cases of TSM with a trisomy 18 karyotype, and only
two of these were phenotypically female with 45,X/47,XY,+18 karyotype. We present
the case of a phenotypically female infant born with dysmorphic features. G
banded karyotype and interphase FISH of blood showed 45,X in 95% and 47,XY,+18
(trisomy 18) in 5% of cells analysed. However, interphase FISH of buccal cells
showed only the presence of the 45,X cell line. Due to the presence of Y
chromosome material, elective gonadectomy was performed at 13 months of age.
There were bilateral streak ovaries with early evidence of GB bilaterally, a
rudimentary uterus and bilateral fallopian tubes with unilateral ectopic adrenal
tissue identified histologically. Interphase FISH of the gonadal tissue was
similar to the blood findings with 45,X in 86% of cells and 47,XY,+18 in 14% of
cells analysed. This case highlights a rare karyotype of TSM and trisomy 18 in
the same patient and is the first reporting the associated finding of bilateral
GB.
PMID- 27614982
TI - CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus
erythematosus patients.
AB - Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are
missing. Plasma samples of nine SLE patients with known pulmonary involvement
(SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested
by multiplex microarray analysis for various cyto- and chemokines. Significantly
decreased lung function paramters for forced vital capacity (FVC), total lung
capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO
corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE
patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10
(IP-10) levels were significantly higher in SLEpulm, than in patients without
pulmonary manifestations. CCL21 correlated negatively with DLCO ( r = -0.73; p <
0.01) and KLCO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory
volume one second. Receiver Operating Characteristics (ROC) analysis confirmed
high sensitivity and specificity for the separation of SLE patients with and
without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC):
0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82;
sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations
in SLE patients associated with lung functional and DLCO/KLCO changes and were
associated with significant increase in CCL21 and IP-10. These chemokines might
serve as potential biomarkers of lung involvement in SLE patients.
PMID- 27614984
TI - [Specific antibody deficiency: Primary immunodeficiency associated to respiratory
allergy].
AB - : Specific antibody deficiency (SAD) with normal immunoglobulin and normal B
cells is a primary immunodeficiency characterized by reduced ability to produce
antibodies to specific antigens especially polysaccharides. OBJECTIVE: To
describe the characteristics of patients diagnosed with SAD emphasizing the
association between primary immunodeficiency and allergic diseases. PATIENTS AND
METHOD: Descriptive study showing patients with SAD treated at a public hospital
between August 2007 and July 2015. Other secondary or primary immunodeficiency
was discarded. The diagnosis of SAD was based on recurrent infections and
abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG
to 10 pneumococcal serotypes. RESULTS: Twelve patients were included, 4 males,
mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other
respiratory and invasive infections. All patients with SAD had associated asthma,
11 had allergic rhinitis, and other allergies. Three patients did not respond to
any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and
those who responded were with low titers. Treatment with conjugate pneumococcal
vaccine was favorable in 11/12 patients. CONCLUSION: In children older than 2
years with recurrent respiratory infections or invasive S. pneumoniae infections
with normal immunoglobulin we recommend to investigate SAD, especially if they
have a concurrent allergic disease.
PMID- 27614985
TI - Stoichiometric evaluation of partial nitritation, anammox and denitrification
processes in a sequencing batch reactor and interpretation of online monitoring
parameters.
AB - A laboratory-scale sequencing batch reactor (SBR) performing partial nitritation
anammox and denitrification was used to treat anaerobic digester effluents. The
SBR cycle consisted of a short mixing filling phase followed by oxic and anoxic
reaction phases. Working at 25 degrees C, an ammonium conversion efficiency of
96.5%, a total nitrogen removal efficiency of 88.6%, and an organic carbon
removal efficiency of 63.5% were obtained at a nitrogen loading rate of 0.15 kg N
m-3 d-1, and a biodegradable organic carbon to nitrogen ratio of 0.37. The
potential contribution of each biological process was evaluated by using a
stoichiometric model. The nitritation contribution decreased as the temperature
decreased, while the contribution from anammox depended on the wastewater type
and soluble carbon to nitrogen ratio. Denitrification improved the total nitrogen
removal efficiency, and it was influenced by the biodegradable organic carbon to
nitrogen ratio. The characteristic patterns of conductivity, oxidation-reduction
potential (ORP) and pH in the SBR cycle were well related to biological
processes. Conductivity profiles were found to be directly related to the
decreasing profiles of ammonium. Positive ORP values at the end of the anoxic
phases were detected for total nitrogen removal efficiency of lower than 85%, and
the occurrence of bending points on the ORP curves during the anoxic phases was
associated with nitrite depletion by the anammox process.
PMID- 27614986
TI - Risk of ingesting As, Cd, and Pb in animal products in north Rio de Janeiro
state, Brazil.
AB - This study evaluated the levels of As, Cd, and Pb in muscle and liver the cattle
and chicken. The risk was estimated for the adult population of a midsized city
in southeast Brazil, concerning the tolerable ingestion and cancer risk. Samples
of muscle and liver (cattle and chicken) were collected (n = 250). Samples of
mineral supplements for cattle (n = 4) and chicken feed samples (n = 4) were
evaluated as one of many potential source of contamination. Muscle, liver,
mineral supplement, and feed samples were dissolved in acid medium and analyzed
by ICP-OES. Daily muscle and liver intake was estimated using a questionnaire (N
= 427). Daily intake of trace elements by the population based on the consumption
of cattle muscle, cattle liver, chicken muscle, and chicken liver was low,
corresponding to 2.76%, 0.33%, 2.12%, and 0.22% of the Tolerable Intake defined
by the WHO for As; 0.54%, 0.29% 0.55%, 0.01%, for Cd; and 0.80%, 0.07%, 0.62%,
0.02%, for Pb. The mean of total ingestion of As, Cd and Pb was 5.43%, 1.18% and
1.51%, respectively of Tolerable Intake defined by WHO. Cancer risk was lower
than 5 * 10-5 year-1. The results indicate that the muscle and liver consumption
is a source of As, Cd, and Pb. Consumers that ingest cattle and chicken muscle
need attention in terms the risk of cancer related to intake of As and Cd. Feed
and mineral supplementation remain as one of many sources of exposure of As, Cd,
and Pb.
PMID- 27614987
TI - Application of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of
Intrauterine Adhesions in Rats.
AB - AIMS: To investigate the therapeutic effects of bone marrow-derived mesenchymal
stem cells (BMSCs) transplantation on intrauterine adhesions (IUA). METHODS:
BMSCs were isolated and labeled by green fluorescence protein. IUA model was
established by mechanical injury. 48 rats were randomly divided into control, IUA
model, BMSCs vein injection and BMSCs intrauterine injection groups (n=12 in each
group). The third generation of BMSCs was injected through tail vein or
intrauterine. Three rats were killed at time 0 h, 7 d, 14 d and 28 d and
bilateral uterus were obtained at each time points for the subseqent experiments.
Morphological changes were determined by hematoxylin-eosin staining or Masson
staining. Estrogen receptor (ER) and progesterone receptor (PR) were detected by
immunohistochemistry. RESULTS: BMSCs were specifically stained by CD44 and CD90,
but not by CD45. Before treatment, the numbers of endometrial glands were
significantly decreased, while fibrosis area rate was increased in IUA model
group (P<0.05 vs Control). Meanwhile, ER expression, but not PR was significantly
up-regulated in model group (P<0.05 vs Control). By contrast, the therapies by
BMSCs transplantation through either tail vein injection or intrauterine
injection significantly elevated the numbers of endometrial glands and decreased
the fibrosis area rate (P<0.05 vs Model). Moreover, both ER and PR were
remarkably up-regulated after BMSCs transplantation (P<0.05 vs Model). The
therapeutic effect attained to optimal level 1 or 2 weeks after transplantation.
CONCLUSION: BMSCs transplantation was effective to repair the damaged endometrium
likely through promoting the ER and PR expressions.
PMID- 27614988
TI - Multitargeted Kinase Inhibition in Metastatic Differentiated Radioiodine
Refractory Thyroid Cancer: A Look at New Therapeutic Options for a Rare Disease.
AB - BACKGROUND: Metastatic differentiated thyroid cancer (DTC) is a rare disease that
is in the first line treated with iodine-131 radioisotope therapy. Until
recently, options were very limited in the case of progressive radioactive-iodine
(RAI)-refractory disease. Based on new study results, tyrosine kinase inhibitors
(TKIs) have attracted attention. The TKI sorafenib demonstrated significantly
improved progression-free survival (PFS) in a phase III trial. Recent data from
another phase III trial showed that the TKI lenvatinib achieved high response
rates and a large improvement in PFS in metastatic RAI-refractory DTC patients in
the first-line setting and after 1 prior line of TKI. However, little is known
about the response to lenvatinib in patients pretreated with multiple lines of
TKIs. CASE REPORT: We present the case of a 45-year-old man with metastatic RAI
refractory DTC progressing after multiple prior treatments with TKIs and
chemotherapy. A very good and long-lasting response to lenvatinib was observed.
Careful and prospective monitoring as well as management of side effects
including dose adaptation were necessary to ensure success of treatment.
CONCLUSION: Here, we review different novel treatment options for patients with
metastatic RAI-refractory DTC.
PMID- 27614989
TI - Nebulized versus Standard Local Application of Lidocaine during Flexible
Bronchoscopy: A Randomized Controlled Trial.
AB - BACKGROUND: Endobronchial administration of local anesthetics such as lidocaine
is often used for cough suppression during bronchoscopy. To achieve a better
distribution of lidocaine in the tracheobronchial tree, spray catheters have been
developed, allowing nebulization of the local anesthetic solution. However, there
are little data on the efficacy and safety of this approach, or on the
consumption of sedative drugs and lidocaine during nebulized administration.
OBJECTIVES: To investigate the tolerability of nebulized lidocaine compared to
conventional lidocaine administration via syringe through the working channel of
the bronchoscope in patients undergoing bronchoscopy. Consumption of sedative
drugs and lidocaine was also compared between the two lidocaine administration
approaches. METHODS: Patients requiring bronchoscopy with endobronchial or
transbronchial biopsy were randomly assigned to receive topical lidocaine either
via syringe or via nebulizer. Endpoints were consumption of lidocaine and
sedative drugs, as well as patient tolerance and safety. RESULTS: Thirty patients
were included, 15 in each group. Patients in the nebulizer group required lower
doses of endobronchial lidocaine (184.7 +/- 67.98 vs. 250.7 +/- 21.65 mg, p =
0.0045) and intravenous fentanyl (0.033 +/- 0.041 vs. 0.067 +/- 0.045 mg, p =
0.0236) than those in the syringe group; midazolam or propofol dosages did not
differ between the two groups. In addition, there were no between-group
differences in patient tolerance or safety (all p > 0.05). CONCLUSION:
Endobronchial administration of lidocaine during bronchoscopy via nebulizer was
found to be well tolerated and safe and was associated with reduced lidocaine and
fentanyl dosages compared to administration via syringe.
PMID- 27614990
TI - Characteristics of Hyperautofluorescent Choroidal Vessels Using Fundus Camera
Type Short-Wavelength Autofluorescence.
AB - PURPOSE: To clarify differences between eyes showing hyperautofluorescent
choroidal vessels in both nasal and temporal, or only the nasal, portions of the
fundus using fundus autofluorescence. METHODS: Nineteen eyes with
hyperautofluorescent vessels in both nasal and temporal portions (group 1) and 17
only the nasal portion (group 2) of the fundus were studied. Choroidal and
retinal thicknesses (foveal, and nasal and temporal 3,000 um from the fovea),
axial length, and refraction were compared between the two groups. RESULTS: In
group 1, the average foveal, nasal, and temporal choroidal thicknesses (mean +/-
SD) were 69.0 +/- 30.9, 57.1 +/- 18.7, and 88.3 +/- 30.4 MUm, retinal thicknesses
170.1 +/- 48.5, 221.9 +/- 46.5, and 209.5 +/- 37.9 MUm, axial length 28.2 +/- 2.2
mm, and refraction -9.9 +/- 5.9 dpt. In group 2, the respective values were 174.8
+/- 43.0, 80.5 +/- 20.9, and 173.5 +/- 46.1 MUm, 213.4 +/- 29.8, 278.3 +/- 20.2,
and 252.8 +/- 19.6 MUm, 24.2 +/- 1.4 mm, and -1.8 +/- 3.8 dpt. There were
significant between-group differences for all items (p < 0.05). CONCLUSIONS:
Fundus autofluorescence tends to be associated with the detection of
hyperautofluorescent choroidal vessels in eyes with strong myopia or greater
axial length.
PMID- 27614991
TI - Radiotherapy of Cervical Cancer.
AB - Curative-intent radical radiotherapy of cervical cancer consists of external-beam
radiotherapy, brachytherapy, and concomitant chemotherapy with cisplatin. For
each element, new developments aim to improve tumor control rates or treatment
tolerance. Intensity-modulated radiotherapy (IMRT) has been shown to reduce
gastrointestinal toxicity and can be used to selectively increase the
radiotherapy dose. Individualized, image-guided brachytherapy enables better
adaptation of high-dose volumes to the tumor extension. Intensification of
concomitant or sequential systemic therapy is under evaluation.
PMID- 27614993
TI - Clinical Use of Plethysmography in the Diagnosis of Deep Venous Thrombosis and
Arterial Occlusive Disease: Part 1.
AB - This two-part study deals with the clinical use of an ECG-triggered venous
occlusion plethysmograph, the "Periflow." This first part describes procedures
for arterial and for venous examination. Methodologic and technological
improvement over former VOP devices is indicated. And results of investigation on
arterial pathology in 99 patients versus 76 normal subjects are evaluated.(Venous
pathology will be treated in a second paper.)From this study it can be concluded
that most significant information about arterial status is obtained by analyzing
the time-related course of a reactive hyperemia that has to clear off an
experimentally induced arterial debt. The reliability of the qualitative
diagnostic differentiation and of the quantitative assessment is determined by
the proposed parameter handling in order to judge the method's suitability for
objective diagnosis and follow-up of patients with peripheral vascular diseases.
PMID- 27614992
TI - Cervical human papilloma virus (HPV) DNA primary screening test: Results of a
population-based screening programme in central Italy.
AB - Objective To present the results of the first and second round human papilloma
virus (HPV)-based screening programme in the Umbria region after three years.
Methods From August 2010 to November 2011, the entire female population aged 35
64 in a local health district was invited for HPV testing (HPV-DNA cobas4800 on a
liquid-based cytology sample). HPV-negative women were re-invited after three
years. For HPV-positive women, a slide was prepared and interpreted. Positive
cytologies were referred to colposcopy; negatives were referred to repeat HPV
after one year. If HPV was persistently positive, women were referred to
colposcopy; if negative, to normal screening. Indicators of the first and second
round are compared with those of cytology screening in the same area in the
preceding three years. Results Participation was 56.5%, the same as cytology
(56.6%). HPV-positivity was 6.4% (396/6272), cytology triage positivity was
35.6%; 251 cytology negative women were referred to one-year HPV retesting, 84.1%
complied, and 55.5% were positive. Total colposcopy referral was 4.1%, and for
cytology 1%. The detection rate for cervical intraepithelial neoplasia grade 2 or
more severe was 100/00, compared with 3.70/00 using cytology. After three years,
HPV-positivity was 3.4% (129/3831), overall colposcopy referral was 2.3% (most at
one-year follow-up), and detection rate was 0.5/1000. Conclusions The first round
detection rate was more than twice that of cytology screening, while colposcopy
referral increased fourfold. At the second round, the detection rate decreased
dramatically, showing that longer interval and more conservative protocols are
needed.
PMID- 27614994
TI - Small-Vessel Disease: Diabetic Microangiopathy.
PMID- 27614995
TI - An Update on the Diagnosis of Diabetes.
AB - This update on the diagnosis of carbohydrate metabolism abnormalities focuses on
a more rational evaluation of glucose metabolism with a clear line of demarcation
between overt diabetes and impaired glucose tolerance levels. This approach has
eliminated the confusion over a definition of mild asymptomatic diabetes in
contradistinction to overt disease. In addition, there is a limited promise of
diagnosis in certain instances by means of hemoglobin 1 AC determinations.
PMID- 27614996
TI - Management of Diabetic Retinopathy: An Overview.
PMID- 27614997
TI - From Ninety to One Hundred and Six.
PMID- 27614998
TI - Capillary Ultrastructure in Thermally Stressed Paired Digital Biopsies in Man.
AB - Two digital biopsies were removed from the fingertips of each of 5 subjects--one
in a cold environment and the other in a warm environment. Electronmicroscopic
examination of the capillaries within the dermis revealed a pleated, contracted
endothelial lining in the cold, with encroachment of the lumen by projecting
nuclei and cytoplasm. Biopsies from the warm fingertips were dilated in
appearance and had more microvillous processes and vesicles.Contraction and
dilation of capillaries under physiologic thermal variation would appear to
result from swelling of endothelium and consequent occlusion of the lumen.
PMID- 27614999
TI - Aortobronchial Fistula: Keys to Successful Management.
AB - Aortobronchial fistula is a rare but highly lethal condition. If it is
diagnosed,survival rates are greater than 80%; if not, the condition is uniformly
fatal with death usually due to massive hemoptysis. A high index of suspicion is
necessary to establish the diagnosis. The most consistent symptoms are
hemoptysis(96%) and massive hemoptysis (79%). The most rewarding test is a
thoracic aortogram (with a sensitivity of 71 %). Characteristics of this
condition, as described in the literature, and an illustrative case are
presented.
PMID- 27615000
TI - Effect of the Kallikrein Inhibitor Aprotinin on Myocardial Ischemia and Necrosis
in Man.
AB - The effect of administration of aprotinin, a serine esterase inhibitor capable of
inactivating kallikrein, on the extent and severity of acute myocardial ischemic
injury and subsequent necrosis, was studied in 25 patients. Another group of 25
patients who did not receive aprotinin served as a control group.We administered
100,000 kallikrein inhibitor units (KIU) of aprotinin as a bolus dose, followed
by a continuous infusion (4 ml/min) that contained 10,000 KIU/kg in 240 ml of
dextrose/water solution, to all 25 patients admitted to the hospital within 30 to
60 minutes after the onset of acute myocardial ischemia.To measure the effect of
aprotinin, three parameters were studied; the sum of S-T segment elevations
(SigmaST), the development of Q waves, and the prediction of infarct size by
measuring the disappearance rate of creatine phosphokinase(MB CPK isoenzyme).The
average SigmaST in the treated group decreased from 40.5 +/- 7.00 mv to 12.95 +/
4.60 mv (P < 0.01); in contrast the control group's SigmaST did not change
significantly, from 54.25 +/- 8.02 to 51.7 +/- 6.8. Deeper Q waves evolved in the
control group compared to the treated group: DeltaQ (6 hours) = 1.0 ST (15 min)
+1.19 (25 patients, r = 0.78); and in the treated group DeltaQ (6 hours) = 0.66
ST (15min) + 0.91 (25 patients, r = 0.65) (P < 0.025).In the control group the
estimated infarct size was 57.4 +/- 4 CPK-gram equivalents(CPK-g-Eq). There was
significantly less damage in the treated group: 19 +/- 2 CPK-g-Eq (P < 0.01).
Thus we conclude that aprotinin diminishes myocardial damage.
PMID- 27615001
TI - The Pathology of Sympathetic Ganglia and Peripheral Nerve in Diabetic and
Nondiabetic Atherosclerotic Patients: A Comparative Study.
PMID- 27615002
TI - Cardiomyopathy in Diabetes Mellitus.
PMID- 27615003
TI - Myocardial Infarction in a Young Woman With Systemic Lupus Erythematosus Talma.
AB - We describe the case of a young woman with systemic lupus erythematosus (SLE)who
suffered an acute myocardial infarction(MI). The patient was treated by cortico
steroids in addition to the usual management for acute MI. The role of arteritis
in producing the infarction is also discussed.
PMID- 27615004
TI - p38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against
graphene oxide toxicity in Caenorhabditis elegans.
AB - Biological barrier plays a crucial role for organisms against the possible
toxicity from engineered nanomaterials (ENMs). Graphene oxide (GO) has been
proven to cause potential toxicity on organisms. However, the molecular
mechanisms for intestinal barrier of animals against GO toxicity are largely
unclear. Using in vivo assay system of Caenorhabditis elegans, we found that
mutation of genes encoding core p38 mitogen-activated protein kinase (MAPK)
signaling pathway caused susceptible property to GO toxicity and enhanced
translocation of GO into the body of nematodes. Genetic assays indicated that SKN
1/Nrf functioned downstream of p38 MAPK signaling pathway to regulate GO toxicity
and translocation. Transcription factor of SKN-1 could regulate GO toxicity and
translocation at least through function of its targeted gene of gst-4 encoding
one of phase II detoxification proteins. Moreover, intestine-specific RNA
interference (RNAi) assay demonstrated that the p38 MAPK-SKN-1/Nrf signaling
cascade could function in intestine to regulate GO toxicity and intestinal
permeability in GO exposed nematodes. Therefore, p38 MAPK-SKN-1/Nrf signaling
cascade may act as an important molecular basis for intestinal barrier against GO
toxicity in organisms. Exposure to GO induced significantly increased expression
of genes encoding p38 MAPK-SKN-1/Nrf signaling cascade, which further implies
that the identified p38 MAPK-SKN-1/Nrf signaling cascade may encode a protection
mechanism for nematodes in intestine to be against GO toxicity.
PMID- 27615006
TI - Relationship of microRNA 616 gene polymorphism with prognosis of patients with
premature coronary artery disease.
AB - OBJECTIVE: To investigate the relationship of microRNA 616 (has-miR-616) single
nucleotide polymorphisms (SNPs) and its target gene paraoxonase 1 (PON 1) with
the prognosis of patients with premature coronary artery disease (pCAD). METHODS:
266 pCAD cases in the case group and 300 cases in the control group were
collected. Using the polymorphism method of polymerase chain reaction and
restriction fragment length, the has-miR-616 rs3735590 genotypes of target gene
PON 1 were detected. RESULTS: In the changes of rs3735590 C/T SNPs, compared with
CC genotypes, the risk of coronary heart disease of the individuals carrying CT
and TT genotypes were reduced by 42% and 31%, respectively (p < 0.05). The risk
of developing coronary heart disease in individuals carrying CT and TT genotypes
were reduced significantly in the population with levels of total cholesterol,
high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.
CONCLUSION: Target gene PON 1 of hsa-miRNA-616 rs3735590C-T SNPs is associated
with the reduced incidence risk of pCAD, and carrying C alleles is an independent
risk factor for pCAD.
PMID- 27615005
TI - Research on radiotherapy at different times of the day for inoperable cervical
cancer.
AB - PURPOSE: To investigate the radiation effects and acute damage in inoperable
cervical cancer patients irradiated at different times as well as the underlying
mechanisms. METHODS: 67 patients were randomized to a morning group (MG, 9:00 -
11:00 AM) and an evening group (EG, 9:00 - 11:00 PM) and both received external
beam radiotherapy (RT) (50 Gy in 25 fractions) at different times. Brachytherapy
(36 - 42 Gy in 6 - 7 fractions) was also performed to enhance the radiation
response twice every week in all patients at the same time. Clinical therapeutic
effects and acute toxicities were evaluated after RT. Flow cytometry was analyzed
before and after RT. RESULTS: Patients' response to radiation was similar in the
two groups. Incidences of overall and high-grade (III - IV) diarrhea in the MG
vs. the EG were 75.0% vs. 57.6% and 12.5% vs. 6.1%, respectively. The incidence
of severe hematological toxicity in the EG was significantly increased compared
to the MG group. Cell apoptosis in the EG was significantly higher at 9:00 -
11:00 PM than that at 9:00 - 11:00 AM after RT. No significant differences were
found in Gap Phase 0/Gap Phase 1 (G0/G1), Gap Phase 2/Metaphase Phase (G2/M), and
Synthesis Phase (S) phase between different times and groups, nor were
expressions of Per1, Per2, and Clock. But expressions of Per1, Per2, and Clock
were significantly negative with G2/M phase and positively correlated with cell
apoptosis. CONCLUSION: RT at different time intervals results in similar
efficacy. However, RT in the morning reduces severe hematological toxicity.
Radiation responses may be associated with circadian genes by influence of cell
cycles and apoptosis.?.
PMID- 27615008
TI - Predictors of response to ipragliflozin treatment in patients with type 2
diabetes mellitus.
AB - OBJECTIVE: The aim of the present study was to investigate the efficacy and
safety of ipragliflozin treatment on glycemic control in patients with type 2
diabetes mellitus (T2DM). METHODS: We recruited 44 patients with T2DM, treated
them with 50 mg/day of ipragliflozin for 12 weeks, and assessed several diabetic
variables before and after treatment. We used stepwise multiple regression
analysis to evaluate response to ipragliflozin in terms of changes in hemoglobin
A1c (HbA1c) levels after therapy. RESULTS: Treatment with ipragliflozin for 12
weeks significantly decreased fasting glucose, HbA1c, and blood pressure levels
without severe adverse events. The baseline HbA1c (beta = -0.52, p < 0.01) and
alanine aminotransferase (ALT) levels (beta = -0.29, p = 0.03) were independently
and significantly related to a decrease in HbA1c levels. CONCLUSIONS: In patients
with T2DM, ipragliflozin treatment improved glycemic control, and baseline HbA1c
and ALT levels appeared to predict treatment response.
PMID- 27615007
TI - A bioequivalence study of two omeprazole formulations in healthy male volunteers.
AB - OBJECTIVE: This study had a single-dose, randomized, open-label, 2-period, and 2
sequence crossover design to evaluate pharmacokinetic (PK) bioequivalence between
the test and reference formulations. METHODS AND MATERIALS: Of the 34 healthy
male volunteers enrolled, 4 were excluded owing to consent withdrawal before drug
administration and the remaining 30 subjects were administered 20 mg each of the
test and reference formulations of omeprazole. The blood samples for PK analysis
were collected at the scheduled time-points, prior to dosing to 10 hours after
dosing. Plasma concentrations of omeprazole were quantified by a liquid
chromatography-tandem mass spectrometry method. Bioequivalence was assessed
according to current guidelines issued by regulatory authorities. RESULTS: The
plasma concentration-time profiles of omeprazole were similar between the
reference and test drugs. The geometric mean ratios (90% confidence interval: CI)
of test to reference were 0.9104 (0.8538 - 0.9708) for peak plasma concentration
(Cmax) and 0.9304 (0.8836 - 0.9796) for area under the plasma
concentration-time curve from time zero to time of last measureable concentration
(AUC0-t). CONCLUSION: The results from the PK analysis suggested that
the reference and test formulations of 20 mg omeprazole capsules were
bioequivalent in healthy male subjects.
PMID- 27615009
TI - Erratum to: Attenuation of Abeta toxicity by promotion of mitochondrial fusion in
neuroblastoma cells by liquiritigenin.
PMID- 27615010
TI - Synthesis, structural characterization and biological evaluation of 4'-C-methyl-
and phenyl-dioxolane pyrimidine and purine nucleosides.
AB - Nucleoside analogues play an important role in antiviral, antibacterial and
antineoplastic chemotherapy. Herein we report the synthesis, structural
characterization and biological activity of some 4'-C -methyl- and -phenyl
dioxolane-based nucleosides. In particular, alpha and beta anomers of all natural
nucleosides were obtained and characterized by NMR, HR-MS and X-ray
crystallography. The compounds were tested for antimicrobial activity against
some representative human pathogenic fungi, bacteria and viruses. Antitumor
activity was evaluated in a large variety of human cancer cell-lines. Although
most of the compounds showed non-significant activity, 23alpha weakly inhibited
HIV-1 multiplication. Moreover, 22alpha and 32alpha demonstrated a residual
antineoplastic activity, interestingly linked to the unnatural alpha
configuration. These results may provide structural insights for the design of
active antiviral and antitumor agents.
PMID- 27615011
TI - A super twin T-DNA vector that allows independent gene expression during
Agrobacterium-mediated transformation.
AB - In this study, we designed and constructed a super twin T-DNA vector (pTRIDT313
g) containing two independent T-DNA cassettes-one for the selection gene Hyg and
the other for the target gene Gus-to produce marker-free transgenic lines. The
resulting vector was transformed into tobacco, and polymerase chain reaction
(PCR) analysis showed four types of gene combinations in the T1 and T2
generations: Gus only, Hyg only, Gus+Hyg, and untransformed lines. The
intermediate region from the T-DNA of the right border of Hyg to the left border
of Gus in the Hyg and Gus lines was not amplified. Genome walking confirmed that
the Hyg and Gus T-DNA cassettes were independently inserted in different regions
of the tobacco genome. Thus, the two T-DNA cassettes were integrated randomly as
independent loci into the tobacco genome. The results of reverse transcription
PCR indicated that Hyg could normally be expressed in the roots, stems, and
leaves of transgenic lines, and the resistance test showed that all Hyg
transgenic lines could grow in the presence of 50mg/L hygromycin. All Gus
transgenic lines showed obvious blue coloration in enzyme activity tests,
indicating that the Gus gene could be normally expressed in all the lines.
Therefore, the super twin T-DNA vector (pTRIDT313-g) exhibits independent
integration, heredity, and normal gene function from two T-DNA cassettes. This
vector could be a useful and valuable tool in the production of marker-free
transgenic lines.
PMID- 27615013
TI - Is the use of renin-angiotensin system inhibitors in patients with aortic valve
stenosis safe and of prognostic benefit? A systematic review and meta-analysis.
AB - Aortic valve stenosis (AVS) is associated with significant morbidity and
mortality, especially in the presence of symptoms and echocardiographic signs of
left ventricular remodelling (i.e. increase in left ventricular mass, left
ventricular dilation, and systolic dysfunction). Renin-angiotensin system
inhibitors (RASi) attenuate cardiac remodelling in various conditions, but the
safety and efficacy of RASi in AVS is unsure. We performed a systematic review
and meta-analysis to address these issues. We identified three smaller randomized
clinical trials and five observational studies eligible for inclusion (PubMed,
EMBASE, and Cochrane library search criteria: aortic stenosis, aortic valve,
angiotensin-converting enzyme inhibitor in different combinations, published in
English at any time up to 1 April 2016). Our analyses suggested that use of RASi
was safe, with no observed increase in mortality risk [576/3389 patients
receiving RASi vs. 1118/4384 controls died; relative risk 0.93 (95% confidence
interval 0.78-1.11), P = 0.44]. Use of RASi was also observed to lower the risk
of aortic valve replacement (AVR) surgery [67/2913 patients with RASi vs.
154/3666 controls underwent AVR; relative risk 0.68 (95% confidence interval 0.51
0.91), P = 0.01]. In current clinical practice (based on published literature;
mainly observational studies), use of RASi appears to be safe in patients with
AVS and may reduce the need for AVR, but the evidence is overall weak. Large
scale randomized clinical trials are warranted to address whether prescription of
RASi to treatment-naive patients may prevent disease progression, delay AVR
surgery need, and lower the risk of mortality.
PMID- 27615014
TI - Selective Activation of Anticancer Chemotherapy by Cancer-Associated Fibroblasts
in the Tumor Microenvironment.
AB - Background: The tumor microenvironment has recently emerged as a new target of
anticancer chemotherapy. Selective activation of anticancer chemotherapy in the
tumor microenvironment would further reduce the toxicity of anticancer drugs
toward normal tissues. Fibroblast activation protein (FAP) is known to be
selectively overexpressed on cancer-associated fibroblasts (CAFs) in the tumor
microenvironment. Here, we designed an anticancer chemotherapeutic system based
on promelittin, a peptide toxin that is selectively converted from an inactive
form to the pore-forming melittin upon cleavage by FAP in the tumor
microenvironment. Methods: We conjugated promelittin-containing FAP-cleavable
sequences to pegylated phospholipids and anchored them to reduced graphene oxide
(rGO) nanosheets. The resulting nanosheets, PL-rGO, were tested for hemolysis and
used for doxorubicin delivery. In vitro cocultures and in vivo tumor growth (n =
5 mice per group) with tissue immunostaining were used to test the selective
activation of anticancer chemotherapy by FAP expressed on CAFs. Results: FAP
specific hemolytic activity of PL-rGO was observed in cocultures of CAFs and HT29
cells but not in HT29 cells alone. Doxorubicin-loaded PL-rGO (Dox/PL-rGO) showed
3.4-fold greater cell-killing efficacy (compared with free Dox in the CAF/HT29
coculture system, effects that were not observed in HT29 cells alone).
Intravenously administered Dox/PL-rGO reduced the growth of HT29 tumors more
effectively than other treatments (Dox/PL-rGO: mean = 200.6 mm(3), 95% confidence
interval [CI] = 148.7 to 252.5 mm(3); free Dox: mean = 697.0 mm(3), 95% CI =
646.9 to 747.1 mm(3), PL: mean = 565.0 mm(3), 95% CI = 550.5 to 579.6 mm(3);
Dox/rGO: mean = 637.6 mm(3), 95% CI = 619.5 to 655.7 mm(3); PL-rGO: mean = 464.4
mm(3), 95% CI = 433.0 to 495.8 mm(3)). Immunostaining of tumor tissues revealed
that survival of CAFs and HT29 cells was lowest in the group treated with Dox/PL
rGO. Conclusions: The demonstration of selective activation of PL-rGO by FAP on
CAFs suggests that PL-rGO may serve as a tumor microenvironment-responsive
anticancer chemotherapy system.
PMID- 27615012
TI - Response to second treatment after initial failed treatment in a multicenter
prospective infantile spasms cohort.
AB - OBJECTIVE: Infantile spasms (IS) represent a severe epileptic encephalopathy
presenting in the first 2 years of life. Recommended first-line therapies
(hormonal therapy or vigabatrin) often fail. We evaluated response to second
treatment for IS in children in whom the initial therapy failed to produce both
clinical remission and electrographic resolution of hypsarhythmia and whether
time to treatment was related to outcome. METHODS: The National Infantile Spasms
Consortium established a multicenter, prospective database enrolling infants with
new diagnosis of IS. Children were considered nonresponders to first treatment if
there was no clinical remission or persistence of hypsarhythmia. Treatment was
evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral
corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and
vigabatrin) were compared to all other nonstandard treatments. We compared
response rates using chi-square tests and multivariable logistic regression
models. RESULTS: One hundred eighteen infants were included from 19 centers.
Overall response rate to a second treatment was 37% (n = 44). Children who
received standard medications with differing mechanisms for first and second
treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69
[25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset
had a higher response rate to second treatment than those initially treated later
(36/82 [44%] vs. 8/34 [24%], p = 0.040). SIGNIFICANCE: Greater than one third of
children with IS will respond to a second medication. Choosing a standard
medication (ACTH, oral corticosteroids, or vigabatrin) that has a different
mechanism of action appears to be more effective. Rapid initial treatment
increases the likelihood of response to the second treatment.
PMID- 27615015
TI - Upper gastrointestinal bleeding in a patient with Sjogren syndrome.
AB - A 68-year-old female patient with Sjogren syndrome was admitted with asthenia,
anorexia and weight loss. On the third day of admission, she developed severe
hematemesis. Urgent upper gastrointestinal endoscopy (UGE) showed multiple
gastric and duodenal ulcers, some with active bleeding requiring endoscopic
therapy. The anatomopathologic examination was compatible with gastric and
duodenal infiltration by a diffuse CD20+ large B cell lymphoma with germinal
center B cell-like morphology. And the patient was referred for chemotherapy with
rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. Although
seldom observed, the risk of lymphoma in Sjogren syndrome is up to 44 times
higher than the general population and rises 7 years after diagnosis. We present
a brief case report with interesting iconography.
PMID- 27615016
TI - The missing piece.
AB - A 59-year-old female was admitted due to the suspicion of food impactation after
having eaten bread. An upper endoscopy revealed an indeterminate, bluish foreign
body in the mid esophagus that was extracted with a forceps. After removal, it
was clear that it was a puzzle piece. The patient then recalled that she had been
playing with a puzzle with her granddaughter, while eating bread.
PMID- 27615017
TI - Over-the-scope clip closure of gastrocutaneous fistula.
AB - A 35-year-old female patient, with Batten's disease, submitted to a surgical
gastrostomy in 2005, and had it replaced in 2007, 2011 and 2014 with one with a
filled balloon as its internal retention mechanism. In 2015, she presented to the
emergency room due to stomal enlargement, leakage and chemical dermatitis and
cellulitis. A 12 mm over-the-scope clip was placed, after anchoring the fistula
edges with the twin grasper and suction of the defect into the applicator cap.
Endoscopic resolution of the fistula was achieved.
PMID- 27615018
TI - Non-absorbable suture granuloma mimicking a retroperitoneal metastatic implant in
a patient with sigmoid neoplasm.
AB - The development of a foreign body granuloma from non-absorbable suture is a
relatively uncommon condition, exceptional in the retroperitoneum of patients
operated on for colorectal surgery. We report the case of a patient with a
history of sigmoid neoplasm showing a retroperitoneal nodule on CT and high
activity on PET, mimicking a tumor implant. Pathology found a foreign body
granuloma. Foreign body granuloma from suture is a condition that may look
identical to tumor relapse or metastatic disease on CT and PET scans, thus
requiring pathology confirmation.
PMID- 27615019
TI - Actinomyces infection as a complication of a post-radiotherapy rectal ulcer.
AB - INTRODUCTION: Pelvic radiotherapy is associated with early and late local
complication. Actinomyces bacterium is part of the saprophyte flora, although
some infection underlying factors are known , the pathophysiology of the disease
is still unexplained. Frequently it is involved in oral, gastrointestinal and
respiratory infections. CASE REPORT: We present the description of a clinical
case supported with images. So that we have developed a bibliographical research
in Pubmed data base including the following key words: Ulcer, rectum,
brachitherapy and Actinomyces. The most recent original articles published in the
last teen years, related with the pathology observed in the patient of the case,
were selected. DISCUSSION: Brachitherapy over pelvic beds ( prostate, cervix and
uterus) could be associated with digestive complications specially in the rectum.
Those complications might oscillate from mild inflammatory changes in the mucosa
to serious damages as ulcers and lack of tissue. This situation increase the risk
of opportunistic infections which could endanger the clinical improve of our
patients. We suggest to remember those germen in the diagnosis process in other
to achieve an early diagnosis and to use a targeted treatment.
PMID- 27615020
TI - Rigler triad in gallstone ileus.
AB - Gallstone ileus is an exceptional complication among billiary diseases. It is
defined as an intestinal obstruction caused by a gallstone as it passes through a
bilio-digestive fistula. This is disease with high morbi-mortality, and whose
main contributing factors are the advanced age of the patients, comorbidities and
the delayed diagnosis. Most of the times, it is a postoperative diagnosis and a
high clinical suspicion is essential for an early diagnosis. In patients with
gallstone ileus the abdominal X-ray is frequently nonspecific and to observe a
complete Rigler triad is exceptional.
PMID- 27615021
TI - Recurrence-free and overall survival among elderly stage III colon cancer
patients treated with CAPOX or capecitabine monotherapy.
AB - The aim of this study is to investigate the effects of CAPOX and capecitabine on
recurrence-free survival (RFS) and overall survival (OS) among elderly stage III
colon cancer patients and to evaluate the effect of (non-)completion. Patients
aged >=70 years who underwent resection only or who were subsequently treated
with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS
and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression
adjusted for patient and tumor characteristics. 982 patients were included: 630
underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five
year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60%
(p = 0.91), adjusted HR = 0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p = 0.76),
adjusted HR = 0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS
37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS
and OS did not differ between patients who discontinued CAPOX early and patients
who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR =
1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI
0.70-1.97)). Three-year RFS and OS differed between patients who discontinued
capecitabine early and patients who completed treatment with capecitabine (RFS:
54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p
= 0.01), adjusted HR = 2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine
is associated with improved RFS and OS. The advantage does not differ by regimen.
The addition of oxaliplatin might not be justified in elderly stage III colon
cancer patients.
PMID- 27615022
TI - Priorities for action on the social determinants of health: Empirical evidence on
the strongest associations with life expectancy in 54 low-income countries, 1990
2012.
AB - The WHO Commission on the Social Determinants of Health set out an impressive
collection of policy proposals on the social determinants of health. However, a
serious weakness for securing implementation is the difficulty for policymakers
in identifying priorities for action. The objective of this study is to determine
a small set of the most influential determinants using existing data and an
empirical approach. 45 Indicators from the World Bank's World Development
Indicators are selected to measure attainment for the determinants proposed by
the Commission. Panel data models of life expectancy at birth for 54 low-income
countries over the years 1990-2012 (1188 country-years) are estimated. Each
determinant is subjected to a robustness test using Extreme Bound Analysis, to
determine the stability of its estimated impact on life expectancy. For 20 robust
and significant determinants the magnitude of association with life expectancy is
determined. The largest average increases in life expectancy at 14.5 months per
capita is associated with a one standard deviation reduction in HIV prevalence
among children, followed by advances in gender equality at 9.4 months.
Improvements in life expectancy between 6 and 9 months are associated with
agricultural production, political stability, access to clean water and
sanitation, good governance, and primary school enrolment. Improvements below 6
months are associated with increases in private health expenditure and overseas
development assistance, and control of armed conflict and HIV prevalence among
men. There is no evidence that national income, public spending on healthcare and
education, secondary schooling, terms of international trade, employment, debt
service and relief, out-of-pocket expenditures, agricultural ex- or imports,
lifestock production, foreign investment, urbanization or environmental
degradation are robustly associated with population health. Results provide
support for the relevance of some proposed policies. The findings can inform
priorities for future research and policy action on the social determinants of
health.
PMID- 27615024
TI - Culture-Negative Severe Sepsis: Nationwide Trends and Outcomes.
AB - BACKGROUND: Although 28% to 49% of severe sepsis hospitalizations have been
described as being "culture negative," there are very limited data on the
epidemiology and outcomes of those with culture-negative severe sepsis (CNSS).
The objectives of this study were to investigate the proportion and trends of
CNSS and its association with mortality. METHODS: Using the Nationwide Inpatient
Sample (NIS) database from 2000 to 2010, we identified adults hospitalized with
severe sepsis. Those without any specific organism codes were identified as "with
CNSS." We examined the proportion of CNSS hospitalizations and rates of mortality
associated with it. We also assessed the independent effect of CNSS on mortality.
RESULTS: Of 6,843,279 admissions of patients with severe sepsis, 3,226,406
(47.1%) had culture-negative results. The age-adjusted proportion of CNSS
increased from 33.9% in 2000 to 43.5% in 2010 (P < .001). Those with CNSS had
more comorbidities, acute organ dysfunction (respiratory, cardiac, hepatic, and
renal dysfunction), and in-hospital mortality (34.6% vs 22.7%; P < .001),
although acute kidney injury requiring dialysis was less frequent (5.3% vs 6.1%;
P < .001). CNSS was an independent predictor of mortality in those with severe
sepsis (OR, 1.75; 95% CI, 1.72-1.77). CONCLUSIONS: CNSS among hospitalized
patients is common, and its proportion is on the rise. CNSS is associated with
greater acute organ dysfunction and mortality. Having CNSS is an independent
predictor of death.
PMID- 27615023
TI - Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial
Hypertension: A Systematic Review and Network Meta-Analysis.
AB - BACKGROUND: We conducted a systematic review and network meta-analysis to examine
comparative efficacy and tolerability of pharmacologic interventions for
pulmonary arterial hypertension (PAH). METHODS: MEDLINE, the Cochrane Register,
EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3,
2016). Randomized controlled trials (RCTs) studying the approved pharmacologic
agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors
(PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and
riociguat and selexipag, alone or in combination, for pulmonary arterial
hypertension (PAH) and reporting at least one efficacy outcome were selected.
RESULTS: Thirty-one RCTs with 6,565 patients were selected. In network meta
analysis, when compared with a median placebo rate of 14.5%, clinical worsening
was estimated at 2.8% with riociguat (risk ratio [RR], 0.19; 95% CI, 0.05-0.76);
at 3.9% with ERA + PDE5i (RR, 0.27; 95% CI, 0.14-0.52), and at 5.7% with PDE5i
(RR, 0.39; 95% CI, 0.24-0.62). For improvement in functional status, when
compared with 16.2% in the placebo group, improvement in at least one New York
Heart Association/World Health Organization (NYHA/WHO) functional class was
estimated at 81.8% with IV/SC prostanoids (RR, 5.06; 95% CI, 2.3211.04), at 28.3%
with ERA + PDE5i (RR, 1.75; 95% CI, 1.05-2.92), and at 25.2% with ERA (RR, 1.56;
95% CI, 1.22-2.00). Differences in mortality were not significant. Adverse events
leading to discontinuation of therapy were highest with the PO/INH prostanoids
(RR, 2.92; 95% CI, 1.68-5.06) and selexipag (RR, 2.06; 95% CI, 1.04-3.88)
compared with placebo. CONCLUSIONS: Currently approved pharmacologic agents have
varying effects on morbidity and functional status in patients with PAH. Future
comparative effectiveness trials are warranted with a focus on a patient-centered
approach to therapy. REGISTRATION: PROSPERO CRD42016036803.
PMID- 27615025
TI - STAR: a simple TAL effector assembly reaction using isothermal assembly.
AB - Transcription activator-like effectors (TALEs) contain modular programmable DNA
binding domains. Fusing TALEs with effector domains creates synthetic
transcription factors (TALE-TFs) or nucleases (TALENs), enabling precise gene
manipulations. The construction of TALEs remains challenging due to their
repetitive sequences. Here we report a simple TALE assembly reaction (STAR) that
enables individual laboratories to generate multiple TALEs in a facile manner.
STAR uses an isothermal assembly ('Gibson assembly') that is labour- and cost
effective, accessible, rapid and scalable. A small 68-part fragment library is
employed, and the specific TALE repeat sequence is generated within ~8 hours.
Sequence-verified TALENs or TALE-TF plasmids targeting 17 bp target sequences can
be produced within three days, without the need for stepwise intermediate plasmid
production. We demonstrate the utility of STAR through production of functional
TALE-TFs capable of activating human SOX2 expression. STAR addresses some of the
shortcomings of existing Golden Gate or solid-phase assembly protocols and
enables routine production of TALE-TFs that will complement emerging CRISPR/Cas9
based reagents across diverse applications in mammalian stem cell and synthetic
biology.
PMID- 27615026
TI - Interventions to optimise the care continuum for chronic viral hepatitis: a
systematic review and meta-analyses.
AB - BACKGROUND: Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus
(HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the
effectiveness of these medicines, individuals must be engaged and retained in
care. We analysed operational interventions to enhance chronic viral hepatitis
testing, linkage to care, treatment uptake, adherence, and viral suppression or
cure. METHODS: We did a systematic review of operational interventions, and did
meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO
library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL
for randomised controlled trials and controlled non-randomised studies that
examined operational interventions along the chronic viral hepatitis care
continuum, published in English up to Dec 31, 2014. We included non
pharmaceutical intervention studies with primary or secondary outcomes of
testing, linkage to care, treatment uptake, treatment adherence, treatment
completion, treatment outcome, or viral endpoints. We excluded dissertations and
studies of children only. Data were extracted by two independent reviewers, with
disagreements resolved by a third reviewer. Studies were assessed for bias. Data
from similar interventions were pooled and quality of evidence was assessed using
GRADE. This study was registered in PROSPERO (42014015094). FINDINGS: We
identified 7583 unduplicated studies, and included 56 studies that reported
outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except
one were from high-income countries. Lay health worker HBV test promotion
interventions increased HBV testing rates (relative risk [RR] 2.68, 95% CI 1.82
3.93). Clinician reminders to prompt HCV testing during clinical visits increased
HCV testing rates (3.70, 1.81-7.57). Nurse-led educational interventions improved
HCV treatment completion (1.14, 1.05-1.23) and cure (odds ratio [OR] 1.93, 95% CI
1.44-2.59). Coordinated mental health, substance misuse, and hepatitis treatment
services increased HCV treatment uptake (OR 3.03, 1.24-7.37), adherence (RR 1.22,
1.05-1.41), and cure (RR 1.21, 1.07-1.38) compared with usual care.
INTERPRETATION: Several simple, inexpensive operational interventions can
substantially improve engagement and retention along the chronic viral hepatitis
care continuum. Further operational research to inform scale-up of hepatitis
services is needed in low-income and middle-income countries. FUNDING: World
Health Organization and US Fulbright Program.
PMID- 27615027
TI - Building the evidence base to eliminate hepatitis B and C as public health
threats.
PMID- 27615030
TI - Ethical issues in the evaluation of adults with suspected genetic neuromuscular
disorders.
AB - Genetic testing is rapidly becoming an increasingly significant part of the
diagnostic armamentarium of neuromuscular clinicians. Although technically easy
to order, the results of such testing, whether positive or negative, have
potentially enormous consequences for the individual tested and for family
members. As a result, ethical considerations must be in the forefront of the
physician's agenda when obtaining genetic testing. Informed consent is an
important starting point for discussions between physicians and patients, but the
counseling embedded in the informed consent process must be an ongoing part of
subsequent interactions, including return of results and follow-up. Patient
autonomy, including the right to know and right not-to-know results, must be
respected. Considerations of capacity, physician beneficence and nonmaleficence,
and privacy all play roles in the process. Muscle Nerve 54: 997-1006, 2016.
PMID- 27615028
TI - Sending a message: extracellular vesicles of pathogenic protozoan parasites.
AB - Parasitic unicellular eukaryotes use extracellular vesicles (EVs) as vehicles for
intercellular communication and host manipulation. By using various mechanisms to
generate EVs and by transferring a wide range of molecules through EVs,
pathogenic protozoans are able to establish infective niches, modulate the immune
system of the host and cause disease. In addition to effects on the host, EVs are
able to transfer virulence factors, drug-resistance genes and differentiation
factors between parasites. In this Progress article, we explore recent insights
into the biology of EVs from human infectious protozoan parasites, including
Trichomonas vaginalis, Plasmodium spp. and kinetoplastids, such as Trypanosoma
spp. and Leishmania spp.
PMID- 27615029
TI - Cognitive Priming and Cognitive Training: Immediate and Far Transfer to Academic
Skills in Children.
AB - Cognitive operations are supported by dynamically reconfiguring neural systems
that integrate processing components widely distributed throughout the brain. The
inter-neuronal connections that constitute these systems are powerfully shaped by
environmental input. We evaluated the ability of computer-presented brain
training games done in school to harness this neuroplastic potential and improve
learning in an overall study sample of 583 second-grade children. Doing a 5
minute brain-training game immediately before math or reading curricular content
games increased performance on the curricular content games. Doing three 20
minute brain training sessions per week for four months increased gains on school
administered math and reading achievement tests compared to control classes
tested at the same times without intervening brain training. These results
provide evidence of cognitive priming with immediate effects on learning, and
longer-term brain training with far-transfer or generalized effects on academic
achievement.
PMID- 27615031
TI - Hippocampal strata theta oscillations change their frequency and coupling during
spatial learning.
AB - The theta rhythm is necessary for hippocampal-dependent spatial learning. It has
been proposed that each hippocampal stratum can generate a current theta dipole.
Therefore, considering that each hippocampal circuit (CA1, CA3, and Dentate Gyrus
(DG)) contributes differently to distinct aspects of a spatial memory, the theta
oscillations on each stratum and their couplings may exhibit oscillatory dynamics
associated with different stages of learning. To test this hypothesis, the theta
oscillations from five hippocampal strata were recorded in the rat during
different stages of learning in a Morris maze. The peak power, the relative power
(RP) and the coherence between hippocampal strata were analyzed. The early
acquisition stage of the Morris task was characterized by the predominance of
slow frequency theta activity and high coupling between specific hippocampal
strata at slow frequencies. However, on the last training day, the theta
oscillations were faster in all hippocampal strata, with tighter coupling at fast
frequencies between the CA3 pyramidal stratum and other strata. Our results
suggest that modifications to the theta frequency and its coupling can be a means
by which the hippocampus differentially operates during acquisition and retrieval
states.
PMID- 27615032
TI - CXCR4 activation promotes differentiation of human embryonic stem cells to neural
stem cells.
AB - G protein-coupled receptors (GPCRs) are involved in many fundamental cellular
responses such as growth, death, movement, transcription and excitation. Their
roles in human stem cell neural specialization are not well understood. In this
study, we aimed to identify GPCRs that may play a role in the differentiation of
human embryonic stem cells (hESCs) to neural stem cells (NSCs). Using a feeder
free hESC neural differentiation protocol, we found that the expression of
several chemokine receptors changed dramatically during the hESC/NSC transition.
Especially, the expression of CXCR4 increased approximately 50 folds in NSCs
compared to the original hESCs. CXCR4 agonist SDF-1 promoted, whereas the
antagonist AMD3100 delayed the neural induction process. In consistence with
antagonizing CXCR4, knockdown of CXCR4 in hESCs also blocked the neural induction
and cells with reduced CXCR4 were rarely positive for Nestin and Sox1-staining.
Taken together, our results suggest that CXCR4 is involved in the neural
induction process of hESC and it might be considered as a target to facilitate
NSC production from hESCs in regenerative medicine.
PMID- 27615033
TI - First and second generation antipsychotics differentially affect structural and
functional properties of rat hippocampal neuron synapses.
AB - The therapy of patients suffering the psychiatric disorder schizophrenia requires
the usage of antipsychotic drugs that are classified into two different groups,
the first-generation (FGAs) and the second-generation antipsychotics (SGAs). This
study compares the effects of the two FGAs haloperidol and flupentixol with those
of the SGA olanzapine on synapse formation and synaptic activity of embryonic rat
hippocampal neurons. To this end, the development of perineuronal nets (PNNs),
the formation of synapses and the resulting spontaneous network activity under
control and treatment conditions were studied using an indirect co-culture system
of neurons and astrocytes in completely defined media. The number and extent of
PNNs that consist of extracellular matrix superstructures surrounding synapses
was not altered in hippocampal neurons by exposure to antipsychotic drugs. In
contrast treatment of hippocampal neurons with haloperidol led to a slight
decrease whereas olanzapine induced a significant increase of the number of
structural synapses after 13days. This differential effect concerning synapse
numbers was also reflected in the spontaneous activity of neuronal networks, as
monitored on multielectrode arrays (MEAs). In that context, application of
haloperidol reduced while olanzapine significantly enhanced network activity.
Unexpectedly, flupentixol that is regarded as an FGA caused similar effects than
the SGA olanzapine in that it augmented synapse number as well as network
activity. Our pilot study provides a proof of concept that the neuron-astrocyte
co-culture model can be used to investigate the impact of antipsychotics on
pivotal parameters of neuronal cell biology. Thereby, it may support the
comparative analysis of antipsychotics applied in the therapy of schizophrenia.
PMID- 27615034
TI - Epidemiology of Hemoglobinopathies in the Huzhou Region, Zhejiang Province,
Southeast China.
AB - The aim of the present study was to report the frequency of thalassemia traits
and other hemoglobinopathies in Huzhou City, Zhejiang Province, People's Republic
of China (PRC), and for the future management of hemoglobinopathies. A total of
8578 pregnant women in the Huzhou region was analyzed for thalassemia traits and
other hemoglobinopathies from July 1 2012 to November 30 2015. Complete blood
count (CBC), and hemoglobin (Hb) variant analyses were performed with automatic
counters and capillary electrophoresis (CE). High resolution melting (HRM)
analysis was applied for genetic diagnosis of thalassemia. The prevalence of
patients with the alpha-thalassemia (alpha-thal) trait was 1.01% (87/8578). beta
Thalassemia (beta-thal) was carried by 112 women with a frequency of 1.3%. The
carrier rate of thalassemia genes in the studied samples was nearly 2.32%. We
excluded those without iron studies, with 159 cases as our sample, a total of
63/159 cases (39.6%) also had iron deficiencies. Moreover, Hb E (HBB: c.79G > A),
and Hb D-Punjab (HBB: c.364G > C) were the most common Hb variants after
thalassemia trait with frequencies of 0.16 and 0.06%, respectively. Only two Hb S
(HBB: c.20A > T) carriers were detected in 20 months of screening time. Hb A1c
results could be confidently reported on all cases except the Hb D-Punjab and Hb
E variants. This study provided a detailed prevalence and molecular
characterization of thalassemia in the Huzhou region, and will contribute toward
the development of prevention strategies and reducing excessive health care costs
in this area, allowing better management of hemoglobinopathies.
PMID- 27615035
TI - Extended microbiological characterization of Gottingen minipigs: porcine
cytomegalovirus and other viruses.
AB - BACKGROUND: To prevent transmission of zoonotic microorganisms from pig
transplants to human recipients when performing xenotransplantation using pig
cells, tissues, or organs, donor pigs have to be carefully characterized.
Gottingen minipigs (GoMP) are often used for various biomedical investigations
and are well characterized concerning the presence of numerous bacteria, fungi,
viruses, and parasites. Recently, we studied the prevalence and expression of
porcine endogenous retroviruses and the prevalence of hepatitis E virus (HEV) in
GoMP. Here, we studied the presence of the porcine cytomegalovirus (PCMV) and
porcine lymphotropic herpesviruses (PLHV) and extended testing for hepatitis E
virus (HEV). METHODS: PCR, nested PCR, real-time PCR, real-time RT-PCR, and
Western blot analyses were used to estimate the prevalence of PCMV, PLHV-1, PLHV
2, PLHV-3, and HEV. RESULTS: Using different PCR methods, and different source
materials, PCMV was found in 10 of 26 adult GoMP, which had been derived
originally by cesarean section and kept under specified pathogen-free conditions.
Only highly sensitive methods gave positive results, not methods of lower
sensitivity. The virus load in all positive animals was low (<100-200 copies per
mL). PLHV-1, PLHV-2, and PLHV-3 were not detected by PCR; however, an anti-PLHV
immune response was found in one of 10 animals tested by Western blot analyses.
HEV was detected by RT-PCR in two of nine tested animals, but no anti-HEV immune
response was observed. CONCLUSION: Using highly sensitive methods, PCMV, HEV, and
PLHV were found in some GoMP, suggesting that these viruses may be introduced
through the placenta. The results show that highly sensitive methods are required
to characterize pigs to be used for xenotransplantation to prevent virus
transmission.
PMID- 27615036
TI - High-performance and flexible thermoelectric films by screen printing solution
processed nanoplate crystals.
AB - Screen printing allows for direct conversion of thermoelectric nanocrystals into
flexible energy harvesters and coolers. However, obtaining flexible
thermoelectric materials with high figure of merit ZT through printing is an
exacting challenge due to the difficulties to synthesize high-performance
thermoelectric inks and the poor density and electrical conductivity of the
printed films. Here, we demonstrate high-performance flexible films and devices
by screen printing bismuth telluride based nanocrystal inks synthesized using a
microwave-stimulated wet-chemical method. Thermoelectric films of several tens of
microns thickness were screen printed onto a flexible polyimide substrate
followed by cold compaction and sintering. The n-type films demonstrate a peak ZT
of 0.43 along with superior flexibility, which is among the highest reported ZT
values in flexible thermoelectric materials. A flexible thermoelectric device
fabricated using the printed films produces a high power density of 4.1 mW/cm(2)
with 60 degrees C temperature difference between the hot side and cold side. The
highly scalable and low cost process to fabricate flexible thermoelectric
materials and devices demonstrated here opens up many opportunities to transform
thermoelectric energy harvesting and cooling applications.
PMID- 27615037
TI - A novel immunomodulatory treatment involving mycophenolate mofetil and
corticosteroids for pediatric autoimmune cytopenias.
AB - BACKGROUND: Successful treatment of both pediatric autoimmune hemolytic anemia
(AIHA) and immune thrombocytopenic purpura (ITP), specifically those that are
refractory to first-line therapies, remains unsatisfactory in terms of long-term
remission and medication side effects. Here, we propose a novel combination
therapy of mycophenolate mofetil (MMF), an adjunct immunosuppressive, and short
term corticosteroids for the treatment of persistent or chronic autoimmune
cytopenias in children. This combination may allow for rapid decrease of steroid
usage as well as prolonged count stabilization with minimal toxicity to the
patient. PROCEDURE: Prospective case series of nine patients, six with persistent
or chronic ITP and three with persistent or chronic AIHA, between the ages of 5
and 19 years who are being treated with combination therapy consisting of
corticosteroids and MMF. RESULTS: All patients with ITP (Patients 4-9) and AIHA
(Patients 1-3) met complete response (CR) criteria, as they all initially
achieved platelet counts 100 * 109 l-1 or more or hemoglobin level greater than
or equal to 10 g/dl, respectively, while on combination therapy and then
maintained this level or higher while on MMF alone after steroids were
discontinued. CONCLUSIONS: Our results are very promising, as MMF appears to be
an effective and well-tolerated adjunct immunosuppressant that allows for rapid
weaning of steroid usage, minimal adverse side effects to the patients, and long
term stabilization of counts, a goal that has not been achieved successfully with
other secondary treatment modalities. Therefore, this novel combination therapy
may be an excellent alternative for the treatment of persistent or chronic
autoimmune cytopenias in the pediatric population.
PMID- 27615038
TI - [Stimulation-Oriented Interventions for Behavioral Problems among People with
Dementia: A Systematic Review and Meta-Analysis].
AB - PURPOSE: This study was a systematic review and meta-analysis designed to
investigate the effects of stimulation-oriented interventions for behavioral
problems among people with dementia. METHODS: Based on the guidelines of the
Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), a
literature search was conducted using seven electronic databases, gray
literature, and other sources. Methodological quality was assessed using the
Scottish Intercollegiate Guidelines Network (SIGN) for randomized controlled
trials (RCTs). Data were analyzed using R with the 'meta' package and the
Comprehensive Meta-Analysis (CMA 2.0) program. RESULTS: Sixteen studies were
included for meta-analysis to investigate the effect of stimulation-oriented
interventions. The quality of individual studies was rated as '++' for eight
studies and '+' for the rest. The effect sizes were analyzed according to three
subgroups of interventions (light, music, and others); Hedges' g=0.04 (95% CI:
0.38~0.46), -0.23 (95% CI: -0.56~0.10), -0.34 (95% CI: -0.34~0.00), respectively.
To explore the possible causes of heterogeneity (I2=62.8%), meta-regression was
conducted with covariates of sample size, number of sessions, and length of
session (time). No moderating effects were found for sample size or number of
sessions, but session time showed a significant effect (Z=1.96, 95% CI:
0.00~0.01). Finally, a funnel plot along with Egger's regression test was
performed to check for publication bias, but no significant bias was detected.
CONCLUSION: Based on these findings, stimulation-oriented interventions seem to
have a small effect for behavioral problems among people with dementia. Further
research is needed to identify optimum time of the interventions for behavioral
problems among dementia pateints.
PMID- 27615039
TI - [Development and Effects of Assertiveness Training applying Dongsasub Training
for Nursing Students in Clinical Practice].
AB - PURPOSE: This study was conducted to develop assertiveness training applying
Dongsasub training for junior nursing students, and to verify effectiveness of
the training on assertiveness behavior, self-esteem, clinical practice stress,
and clinical competence. METHODS: The study design was a non-equivalent control
group non-synchronized design. Participants were 63 nursing students in clinical
training (31 students in the experimental group and 32 students in the control
group). The assertiveness training applying Dongsasub training consisted of four
sessions. Outcome variables included assertiveness behavior, self-esteem,
clinical practice stress, and clinical competence. Data were analyzed using Chi
square, Fisher's exact test and independent samples t-test with SPSS/WIN 21.0.
RESULTS: Scores of assertiveness behavior (t=-2.49, p=.015), self-esteem (t=
4.80, p<.001) and clinical competence (t=-2.33, p=.023) were significantly higher
and clinical practice stress (t=4.22, p<.001) was significantly lower in the
experimental group compared to the control group. CONCLUSION: Results indicate
that the assertiveness training applying Dongsasub training can be used as a
nursing intervention to lower clinical practice stress and improve the clinical
competence of nursing students.
PMID- 27615040
TI - [Mixed Method Research Investigating Evidence-Based Practice Self-efficacy,
Course Needs, Barriers, and Facilitators: From the Academic Faculty and Clinical
Nurse Preceptors].
AB - PURPOSE: The current challenges faced by nurses in providing high quality and
evidence-based practice (EBP) supported care require profound changes in nursing
education. To understand the changes needed to strengthen EBP education, the
researchers examined EBP self-efficacy, course needs, barriers, and facilitators
for academic faculty and clinical nurse preceptors to teach EBP in undergraduate
nursing curricula. METHODS: For this study, mixed-method approach was used with
survey data collected from 73 academic faculty members from 54 universities.
Further, 17 clinical nurse preceptors in three academic hospitals provided
qualitative data for exploration of barriers and facilitators to teaching EBP.
Data analysis used SPSS/WIN 21.0 and content analysis. RESULTS: Quantitative data
showed that although the overall level of self-efficacy among faculty was
moderate, the implementation levels were relatively low. Most faculty members
agreed with the need to integrate EBP courses into undergraduate nursing
curricula. The qualitative data showed that the barriers to teaching EBP were
lack of knowledge, skill, and initial investment for teaching EBP; hierarchical,
rules-oriented nursing culture; potential learner overloads in processing EBP;
limited research dissemination and application. Facilitators were identified as
the importance of EBP to the profession of nursing; collaboration in schools and
hospitals; and continuing education in teaching/utilizing EBP. CONCLUSION: The
findings indicate that for successful integration of EBP ni nursing education
there is a need for faculty training and integrated EBP courses.
PMID- 27615041
TI - [Comparison of Effects of Exhalation and Inhalation Breathing Exercises on
Pulmonary Function and Complications in Elderly Patients with Upper-abdominal
Surgery].
AB - PURPOSE: The purpose of this study was to identify the effects of exhalation
breathing exercises using expirometer and that of inhalation breathing exercises
using incentive spirometry on pulmonary function and complications in elderly
patients with upper-abdominal surgery. METHODS: The research design was a
nonequivalent control group non-synchronized design. Participants were 63
patients who underwent upper-abdominal surgery under general anesthesia (32 in
experiment group, 31 in control group). They were recruited at P university
hospital from August 1 to November 30, 2015. Effects were evaluated by measuring
pulmonary functions (Forced Vital Capacity [FVC], Forced Expiratory Volume in 1
second [FEV1]) and pulmonary complications. Data were analyzed using SPSS/WIN
18.0 program. RESULTS: There was no difference in FVC between the experimental
group and the control group, but FEV1 in the experimental group increased
significantly compared to the control group by time change (p=.001). Also, there
were no pulmonary complications in the experimental group but there were 5 cases
(16.1%)(p=.018) in the control group. CONCLUSION: Findings indicate that
exhalation breathing exercises by elderly patients following upper-abdominal
surgery is an effective nursing intervention in enhancing pulmonary function and
preventing pulmonary complications.
PMID- 27615042
TI - [Factors Influencing Musculoskeletal Symptoms in Military Personnel during Basic
Combat Training].
AB - PURPOSE: This study was done to examine physical, psycho-social, and individual
factors influencing musculoskeletal symptoms among Korean military trainees.
METHODS: Using a correlation study design, military trainees who had completed
almost of all the basic combat training (BCT) days were recruited from two
military training units selected by convenience sampling. Data from 415
participants were analyzed. RESULTS: Prevalence of musculoskeletal symptoms was
29.6% defined as a participant having pain or discomfort in one or more body
parts during training hours for more than seven consecutive days. Back/pelvic
(10.8%), knees (10.1%), shoulders (7.7%), feet/toes (5.6%), ankles (4.8%) were
prone to musculoskeletal symptoms. Musculoskeletal symptoms appeared to be
related to physical exertion during BCT, stress during BCT, social support from
fellow trainees, or previous musculoskeletal injuries. In the logistic regression
model, physical exertion during BCT (OR=2.27, 95% CI: 1.42~3.65), stress during
BCT (OR=1.79, 95% CI: 1.15~2.78), and previous musculoskeletal injuries (OR=1.58,
95% CI: 1.01~2.47) were the significant factors affecting prevalence of
musculoskeletal symptoms. CONCLUSION: Findings indicate that physical exertion
and psycho-social stress should be managed to prevent musculoskeletal symptoms in
military trainees with more attention being given to trainees having a history of
musculoskeletal injuries.
PMID- 27615043
TI - [Effect of Observation Window at Peripheral Intravenous Catheter Site on Early
Recognition of Infiltration among Hospitalized Children].
AB - PURPOSE: The aim of this study was to identify the effect of an observation
window (OW) at peripheral intravenous (IV) catheter sites on early detection of
IV infiltration among hospitalized children. METHODS: This was a retrospective
observational study with history control group design. Participants were children
who had IV infiltration after peripheral catheterization when hospitalized from
January to May, 2014 and January to May, 2015 at a children's hospital located in
Yangsan city, Korea. The 193 patients, who were hospitalized from January to May,
2014 formed the control group and did not have OW, and the 167 patients, who were
hospitalized from January to May, 2015 formed the window group and had OW. Data
were analyzed using chi2-test, independent samples t-test and multiple logistic
regression. RESULTS: First stage IV infiltration was 39.5% for the window group
and 25.9% for the control group, which was significantly different (p=.007). The
likelihood of 2nd stage and above IV infiltration decreased by 44% in the window
group, which was significantly different (p=.014). CONCLUSION: OW at the
peripheral IV catheter site was found to be an effective measure in early
recognition of IV infiltration. Considering the effect of OW, we recommend that
nurses should make an OW with transparent dressing during stabilization of the IV
catheter site in hospitalized children in clinical settings.
PMID- 27615044
TI - [Effects of a Facial Muscle Exercise Program including Facial Massage for
Patients with Facial Palsy].
AB - PURPOSE: The purpose of this study was to examine the effects of a facial muscle
exercise program including facial massage on the facial muscle function,
subjective symptoms related to paralysis and depression in patients with facial
palsy. METHODS: This study was a quasi-experimental research with a non
equivalent control group non-synchronized design. Participants were 70 patients
with facial palsy (experimental group 35, control group 35). For the experimental
group, the facial muscular exercise program including facial massage was
performed 20 minutes a day, 3 times a week for two weeks. Data were analyzed
using descriptive statistics, chi2-test, Fisher's exact test and independent
sample t-test with the SPSS 18.0 program. RESULTS: Facial muscular function of
the experimental group improved significantly compared to the control group.
There was no significant difference in symptoms related to paralysis between the
experimental group and control group. The level of depression in the experimental
group was significantly lower than the control group. CONCLUSION: Results suggest
that a facial muscle exercise program including facial massage is an effective
nursing intervention to improve facial muscle function and decrease depression in
patients with facial palsy.
PMID- 27615045
TI - [Factors Influencing Adolescent Lifetime Smoking and Current Smoking in South
Korea: Using data from the 10th (2014) Korea Youth Risk Behavior Web-Based
Survey].
AB - PURPOSE: The purpose of this study was to investigate factors influencing
lifetime smoking and current smoking among adolescents in South Korea. METHODS:
Hierarchical logistic regression was conducted based on complex sample analysis
using statistics from the 10th (2014) Korea Youth Risk Behavior Web-Based Survey.
The study sample comprised 72,060 adolescents aged 12 to 18. RESULTS: The
significant factors influencing adolescent lifetime smoking were female gender,
older age, higher stress, higher weekly allowance, lower economic status, living
apart from parents, parental smoking, sibling smoking, peer smoking, observation
of school personnel smoking, and coed school compared to boys' school. The
significant factors influencing adolescent current smoking were female gender,
older age, higher stress, higher weekly allowance, both higher and lower economic
status compared to middle economic status, living apart from parents, parental
smoking, sibling smoking, peer smoking, observation of school personnel smoking,
and coed school compared to boys' school. CONCLUSION: Factors identified in this
study need to be considered in programs directed at prevention of adolescent
smoking and smoking cessation programs, as well as policies.
PMID- 27615046
TI - [Economic Effect of Home Health Care Services for Community-dwelling Vulnerable
Populations].
AB - PURPOSE: In this study the costs and benefits of a home health care program were
examined to evaluate the economic feasibility of the program. METHODS: The study
participants included 349 patients in the community who had been registered at a
home health care center for 5 years. The costs and benefits of the program were
analyzed using performance data and health data. The benefits were classified as
the effects of pressure ulcer care, skin wound care and catheters management. The
program effect was evaluated on the change of progress using transition
probability. Benefits were divided into direct benefit such as the savings in
medical costs and transportation costs, and indirect benefits which included
saving in productivity loss and lost future income. RESULTS: Participants had an
average of 1.82 health problems. The input cost was KRW 36.8~153.3 million, the
benefit was KRW 95.4~279.7 million. Direct benefits accounted for 53.4%~81.2%,
and was higher than indirect benefits. The net benefit was greater than 0 from
2006 to 2009, and then dropped below 0 in 2010. CONCLUSION: The average net
benefit during 5 years was over 0 and the benefit cost ratoi was over 1.00,
indicating that the home health care program si economical.
PMID- 27615047
TI - [A Structural Equation Model of Pressure Ulcer Prevention Action in Clinical
Nurses].
AB - PURPOSE: The purpose of this study was to construct and test a structural
equation model for pressure ulcer prevention action by clinical nurses. The
Health Belief Model and the Theory of Planned Behavior were used as the basis for
the study. METHODS: A structured questionnaire was completed by 251 clinical
nurses to analyze the relationships between concepts of perceived benefits,
perceived barriers, attitude, subjective norm, perceived control, intention to
perform action and behavior. SPSS 22.0 and AMOS 22.0 programs were used to
analyze the efficiency of the hypothesized model and calculate the direct and
indirect effects of factors affecting pressure ulcer prevention action among
clinical nurses. RESULTS: The model fitness statistics of the hypothetical model
fitted to the recommended levels. Attitude, subjective norm and perceived control
on pressure ulcer prevention action explained 64.2% for intention to perform
prevention action. CONCLUSION: The major findings of this study indicate that it
is essential to recognize improvement in positive attitude for pressure ulcer
prevention action and a need for systematic education programs to increase
perceived control for prevention action.
PMID- 27615048
TI - [Effects on Stress, Problem Solving Ability and Quality of Life of as a Stress
Management Program for Hospitalized Schizophrenic Patients: Based on the Stress,
Appraisal-Coping Model of Lazarus & Folkman].
AB - PURPOSE: The study was done to evaluate the effects a Stress Management Program
(SMP) on stress, problem solving skills, and quality of life for hospitalized
patients with Schizophrenia. METHODS: A mixed method design was used: a
combination of a repeated-measure design with a non-equivalent control group and
qualitative data collection. The participants were 40 patients with schizophrenia
admitted in three psychiatric hospitals. The experimental group (n=20) received
the SMP twice a week for a total of 8 weeks. RESULTS: Study results revealed that
the SMP was effective for stress (F=321.02, p<.001), problem solving ability
(F=246.28, p<.001), and quality of life (F=63.35,p<.001) for hospitalized persons
with schizophrenia. CONCLUSION: The results suggest that a SMP can be an
effective strategy to reduce patients' hospitalization stress, and improve
problem solving skills and quality of life. Therefore, it is recommended that
mental health nurses use this stress management program in clinical practice to
assist adaptation to hospitalization for persons with schizophrenia.
PMID- 27615049
TI - [Effects of Dietary Program based on Self-efficacy Theory on Dietary Adherence,
Physical Indices and Quality of Life for Hemodialysis Patients].
AB - PURPOSE: The purpose of this study was to examine effects of a dietary program
based on self-efficacy theory on dietary adherence, physical status and quality
of life (QoL) in hemodialysis patients. METHODS: A non-equivalent control group
pre-post test design was used. The intervention group received the dietary
program for 8 weeks from August 4 to September 26, 2014. The control group
received only usual care. RESULTS: ANCOVA showed that dietary adherence (F=64.75,
p<.001) was significantly different between the two groups. Serum albumin
(F=12.13, p =.001), interdialytic weight gain (F=56.97, p<.001), calories
(F=15.80, p<.001) as physical status indices were significantly different, but
serum potassium (F=2.69, p=.106) and serum phosphorus (F=1.08, p=.303) showed no
significant difference between the two groups. In terms of health-related QoL,
the physical component scale (F=10.05, p=.002) and the mental component scale
(F=16.66, p<.001) were significantly different between the two groups. In
addition, in terms of diet related QoL, diet level (F=35.33, p<.001) and
satisfaction level (F=15.57, p<.001) were significantly different between the two
groups, but dietary impact level (F=1.23, p =.271) was not significantly
different. CONCLUSION: Findings show that the dietary program based on self
efficacy theory is an effective nursing intervention program to improve adherence
to diet, and to maintain physical status and QoL for hemodialysis patients.
PMID- 27615050
TI - Timely Interventions can Increase Smoking Cessation Rate in Men with Ischemic
Stroke.
AB - PURPOSE: Smoking cessation is strongly recommended for every smoker after
ischemic stroke, but many patients fail to quit smoking. An improved smoking
cessation rate has been reported with intensive behavioral therapy during
hospitalization and supportive contact after discharge. The aim of this study was
to demonstrate the usefulness of the timely interventions for smoking cessation
in men with acute ischemic stroke. METHODS: Patients who participated in the
timely interventions strategy (TI group) were compared with those who received
conventional counseling (CC group). In the TI group, a certified nurse provided
comprehensive education during admission and additional counseling after
discharge. Outcome was measured by point smoking success rate and sustained
smoking cessation rate for 12 months. RESULTS: Participants, 157 men (86 of the
TI group and 71 of the CC group), were enrolled. Mean age was 58.25 +/- 11.23
years and mean initial National Institutes of Health Stroke Scale score was 4.68
+/- 5.46. The TI group showed a higher point smoking success rate compared with
the CC group (p= .003). Multiple logistic regression analysis showed that the TI
group was 2.96-fold (95% CI, 1.43~6.13) more likely to sustain smoking cessation
for 12 months than the CC group. CONCLUSION: Findings indicate that multiple
interventions initiated during hospital stay and regular follow-up after
discharge are more effective than conventional smoking cessation counseling in
men with acute ischemic stroke.
PMID- 27615051
TI - Molecular Dynamics Study of Superelastic Performance of a beta-Si3N4 Nanohelical
Coil.
AB - Superealsticity behavior has been discovered for the beta-Si3N4 nanohelical coil.
By a series of cyclic loading and unloading simulation tests, the nanohelical
coil could elastically recover its original shape after a relatively long axial
tension far beyond the elastic limit, accompanying little residual plastic
deformation. The spring constant is first a steady-state value of 0.72 N m-1 in
the linear stage and then increases dramatically for up to 1.5 N m-1 in the
nonlinear region. The fascinating performance of the nanocoil makes it stand out
from its bulk counterparts in the development of future electronic devices such
as nanoscale elastic energy storage.
PMID- 27615052
TI - A novel missense mutation of CMT2P alters transcription machinery.
AB - OBJECTIVE: Charcot-Marie-Tooth type 2P (CMT2P) has been associated with
frameshift mutations in the RING domain of LRSAM1 (an E3 ligase). This study
describes families with a novel missense mutation of LRSAM1 gene and explores
pathogenic mechanisms of CMT2P. METHODS: Patients with CMT2P were characterized
clinically, electrophysiologically, and genetically. A neuronal model with the
LRSAM1 mutation was created using CRISPR/Cas9 technology. The neuronal cell line
along with fibroblasts isolated from the patients was used to study RNA-binding
proteins. RESULTS: This American family with dominantly inherited axonal
polyneuropathy reveals a phenotype similar to those in previously reported non-US
families. The affected members in our family cosegregated with a novel missense
mutation Cys694Arg that alters a highly conserved cysteine in the RING domain.
This mutation leads to axonal degeneration in the in vitro neuronal cell line.
Moreover, using protein mass spectrometry, we identified a group of RNA-binding
proteins (including FUS, a protein critically involved in motor neuron
degeneration) that interacted with LRSAM1. The interactions were disrupted by the
Cys694Arg mutation, which resulted in reduction of intranuclear RNA-binding
proteins. INTERPRETATION: Our findings suggest that the mutant LRSAM1 may
aberrantly affect the formation of transcription machinery. Given that a similar
mechanism has been reported in motor neuron degeneration of amyotrophic lateral
sclerosis, abnormalities of RNA/RNA-binding protein complex may play a role in
the neuronal degeneration of CMT2P. Ann Neurol 2016;80:834-845.
PMID- 27615053
TI - Phenotype of 7q11.23 duplication: A family clinical series.
AB - Duplication 7q11.23 syndrome is the reciprocal of Williams-Beuren deletion
syndrome. Studies have reported a recognizable phenotype, including autism,
intellectual disability, speech, and language delay, social anxiety, and
behavioral difficulties in these individuals. Previous studies revealed a variety
of craniofacial abnormalities, brain malformations, and cardiac abnormalities,
including aortic dilation. This patient series evaluates five family members aged
2 months to 35 years, all with confirmed 7q11.23 duplication syndrome. All had
characteristic craniofacial findings and joint hyperextensibility, and three
experienced broken bones/fractures with minimal trauma. Other features included
frequent headaches, sleep problems, hydrocephalus, and in two of the children,
mildly dilated aortic root, and ascending aorta. Psychological test results
reveal borderline to low average nonverbal cognitive abilities and speech and
language delays. All five family members with 7q11.23 syndrome meet criteria for
autism spectrum disorder. Adaptive functioning is impaired for all four children,
but higher for the children's father. The infant shows developmental delays in
language and motor skills, but some improvements in reciprocal social behaviors
over time. Two children exhibit hyperactivity and inattention, and the father and
second youngest child exhibit anxiety. This family clinical series contributes to
the growing literature on the phenotype of 7q11.23 microduplication syndrome
across the age range. Physicians are encouraged to urge focused medical
surveillance and intensive early intervention targeting speech-language and
social reciprocity. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615054
TI - Hypertensive emergency presenting with an isolated celiac artery dissection: A
rare case study.
AB - INTRODUCTION: To our knowledge the most recent article on celiac dissection was
published in 2015 and reported 24 known cases of spontaneous isolated celiac
trunk dissection [2]. While some of those cases reported hypertension as a risk
factor, no other case presents as hypertensive emergency with an isolated celiac
artery dissection. PRESENTATION OF CASE: A 43 year-old man with a past medical
history of uncontrolled hypertension, for which he had reportedly been non
compliant with follow-up, presented with complaints of severe, sudden-onset
epigastric pain which was non-radiating and constant for 1 hour prior to arrival.
On CT an intimal flap was noted within the celiac trunk, starting at the origin
and extending into the left gastric, splenic, and the common hepatic arteries.
DISCUSSION: The most common symptom in patients with celiac artery dissection is
acute or chronic epigastric or abdominal pain [2,4,9,11]. The crux of the
diagnosis of this condition relies on contrast enhanced CT. The superiority of
the CT scan is because of the contrast tracking capability [11]. The two most
common risk factors for celiac artery dissection are hypertension followed by
vasculitis. Patients can be managed nonoperatively or with one of a few operative
procedures. Conservative treatment consists of anticoagulants, antihypertensives,
and antiplatelet therapy [2]. CONCLUSION: To the best of our knowledge, we
present the 25th case of isolated celiac artery dissection. This is the first
case of hypertensive emergency induced spontaneous isolated celiac trunk
dissection in literature. Our patient was managed primarily with a labetalol
drip.
PMID- 27615055
TI - Case Report: De Garengeot's hernia. Appendicitis within femoral hernia. Diagnosis
and surgical management.
AB - INTRODUCTION: Abdominal wall hernias remain as one of the most common problems
that the general surgeon has to treat. Although usually straightforward and easy
to diagnose by the experienced hands, obstacles appear when contents of the
hernia sac include organs. The presence of the appendix inside a femoral hernia
(De Garengeot's hernia) is a rare entity which represents multiple challenges,
both diagnostic and therapeutic. CASE PRESENTATION: We present a case of a 36
year-old female patient who originally presented to the ED with abdominal/groin
pain and a new onset of right inguinal swelling. DISCUSSION: Contrary to the
usual presentation, where an appendix is incidentally found during hernia repair,
we were able to make the diagnosis by CT scan before surgery. This placed us on
an ideal standpoint to plan the surgical management. We approached our case
laparoscopic first, where a distally gangrenous appendix was reduced
intraabdominally. As purulent exudates were present on hernial sac, femoral
hernia repair was achieved with McVay techniche. CONCLUSION: Although rare, the
finding of a strangulated appendix within a femoral hernia represents a
challenge. Here we present a case that may guide the surgeon who faces a similar
case in the future.
PMID- 27615056
TI - Hemophilic pseudotumor in a non-hemophilic patient treated with a hybrid
procedure of preoperative embolization of the feeding arteries followed by
surgical resection-A case report.
AB - INTRODUCTION: Hemophilic pseudotumor is a rare but well documented complication
seen in approximately 1-2% of patients with hemophilia. The incidence continues
to decrease, likely because of increasingly sophisticated techniques in managing
factor deficiency. We present a case of hemophilic pseudotumor in a patient
without hemophilia, an exceptionally rare entity, and outline a hybrid approach
to treatment. PRESENTATION OF CASE: The patient presented with a left sided
iliopsoas mass and associated radiculopathy, with a history of a poorly
characterized bleeding diathesis and Noonan's syndrome. He had no history of
trauma and was not being treated with anti-coagulation. Of note, factors VIII, IX
and XI were normal. An open biopsy was consistent with hemophilic pseudotumor.
The patient underwent a hybrid procedure of preoperative embolization of the left
internal iliac and left deep circumflex arteries followed by surgical debridement
and resection, with an excellent outcome. DISCUSSION: Hemophilic pseudotumor is
rarely seen in patients with hemophilia, and even less frequently in patients
without. Trauma is often the inciting event. A high index of clinical suspicion
is required in order to secure the diagnosis, as the radiographic appearance is
non-specific. Our patient had no history of trauma, although we question whether
his underlying bleeding diathesis may have predisposed him to developing the
pseudotumor. Surgery remains the cornerstone of management in these cases.
CONCLUSION: Within the literature, there are only two other cases of hemophilic
pseudotumor occurring in a non-hemophiliac patient, highlighting the rarity of
this case and the associated diagnostic dilemma.
PMID- 27615058
TI - Differential disgust responding in people with cancer and implications for
psychological wellbeing.
AB - OBJECTIVES: Evidence suggests that disgust responses, known to negatively affect
psychological wellbeing, may differ in people with cancer. We performed the first
quantitative investigation of three discrete types of disgust trait - disgust
propensity, sensitivity and self-directed disgust - in people diagnosed with a
broad range of cancers (versus cancer-free controls), and explored their
associations with psychological wellbeing. DESIGN: In a cross-sectional survey
design, 107 participants with heterogeneous cancer diagnoses, recruited from
cancer charities and support groups, were matched with cancer-free controls by
age and gender. OUTCOME MEASURES: Measures of the three disgust traits were taken
alongside measures of anxiety and depression. RESULTS: Disgust sensitivity and
physical self-disgust were significantly higher in the cancer than control
sample, while disgust propensity and behavioural self-disgust were lower. The
disgust traits had a different pattern of associations to psychological wellbeing
across the two groups, with disgust sensitivity predicting depressive symptoms to
a significantly greater extent in the cancer than control group. CONCLUSIONS:
People with cancer differ from matched controls in their disgust responses and
these responses have significant predictive relationships with aspects of their
psychological wellbeing. The results suggest that emotion-based interventions may
be useful for improving psychological wellbeing in people with cancer.
PMID- 27615059
TI - Autoradiographic imaging and quantification of the high-affinity GHB binding
sites in rodent brain using 3H-HOCPCA.
AB - GHB (gamma-hydroxybutyric acid) is a compound endogenous to mammalian brain with
high structural resemblance to GABA. GHB possesses nanomolar-micromolar affinity
for a unique population of binding sites, but the exact nature of these remains
elusive. In this study we utilized the highly selective GHB analogue, 3
hydroxycyclopent-1-enecarboxylic acid (HOCPCA) as a tritiated version (3H-HOCPCA)
to radioactively label the specific GHB high-affinity binding site and gain
further insight into the density, distribution and developmental profile of this
protein. We show that, in low nanomolar concentrations, 3H-HOCPCA displays
excellent signal-to-noise ratios using rodent brain autoradiography, which makes
it a valuable ligand for anatomical quantification of native GHB binding site
levels. Our data confirmed that 3H-HOCPCA labels only the high-affinity specific
GHB binding site, found in high density in cortical and hippocampal regions. The
experiments revealed markedly stronger binding at pH 6.0 (Kd 73.8 nM) compared to
pH 7.4 (Kd 2312 nM), as previously reported for other GHB radioligands but
similar Bmax values. Using 3H-HOCPCA we analyzed the GHB binding protein profile
during mouse brain development. Due to the high sensitivity of this radioligand,
we were able to detect low levels of specific binding already at E15 in mouse
brain, which increased progressively until adulthood. Collectively, we show that
3H-HOCPCA is a highly sensitive radioligand, offering advantages over the
commonly used radioligand 3H-NCS-382, and thus a very suitable in vitro tool for
qualitative and quantitative autoradiography of the GHB high-affinity site.
PMID- 27615057
TI - Fibroblast growth factor 21 correlates with weight loss after vertical sleeve
gastrectomy in adolescents.
AB - OBJECTIVE: Vertical sleeve gastrectomy (VSG) results in weight loss and increased
bile acids (BA) and fibroblast growth factor 19 (FGF19) levels. FGF21 shares
essential cofactors with FGF19, but its physiology early post-VSG has not been
assessed. METHODS: Ten adolescents (17.4 +/- 0.5 years and BMI 51.5 +/- 2.5 kg/m2
) were enrolled. Fasting and postmeal (100 mL EnsureTM) samples (0-120 min) were
collected (pre-VSG [V1], 1 [V2], and 3 months [V3] post-VSG) for analysis of BA,
FGF19, and FGF21. RESULTS: Post-VSG subjects lost weight (V2 11.8 +/- 0.8 kg; V3
21.9 +/- 1.7 kg). BA and FGF19 increased by V2, 143.6% at 30 min and 74.9% at 90
min post-meal, respectively. BA hydrophobicity index also improved by V3, 21.1%
at 30 min post-meal. Interestingly, fasting and 120-min post-meal FGF21 levels at
V2 were increased by 135.7% and 253.9%, respectively, but then returned to
baseline at V3. BA levels correlated with FGF21 at V2 (P = 0.003, r = 0.89), and
body weight lost post-VSG correlated with FGF21 levels (V2; P = 0.012, R = 0.82).
CONCLUSIONS: Expected changes were seen in BA and FGF19 biology after VSG in
adolescents, but novel changes were seen in correlation between the early
postsurgical increase in FGF21 and weight loss, suggesting that FGF21 may play a
role in energy balance postoperatively, and further investigation is warranted.
PMID- 27615060
TI - Evaluation of the rotenone-induced activation of the Nrf2 pathway in a neuronal
model derived from human induced pluripotent stem cells.
AB - Human induced pluripotent stem cells (hiPSCs) are considered as a powerful tool
for drug and chemical screening and development of new in vitro testing
strategies in the field of toxicology, including neurotoxicity evaluation. These
cells are able to expand and efficiently differentiate into different types of
neuronal and glial cells as well as peripheral neurons. These human cells-based
neuronal models serve as test systems for mechanistic studies on different
pathways involved in neurotoxicity. One of the well-known mechanisms that are
activated by chemically-induced oxidative stress is the Nrf2 signaling pathway.
Therefore, in the current study, we evaluated whether Nrf2 signaling machinery is
expressed in human induced pluripotent stem cells (hiPSCs)-derived mixed
neuronal/glial culture and if so whether it becomes activated by rotenone-induced
oxidative stress mediated by complex I inhibition of mitochondrial respiration.
Rotenone was found to induce the activation of Nrf2 signaling particularly at the
highest tested concentration (100 nM), as shown by Nrf2 nuclear translocation and
the up-regulation of the Nrf2-downstream antioxidant enzymes, NQO1 and SRXN1.
Interestingly, exposure to rotenone also increased the number of astroglial cells
in which Nrf2 activation may play an important role in neuroprotection. Moreover,
rotenone caused cell death of dopaminergic neurons since a decreased percentage
of tyrosine hydroxylase (TH+) cells was observed. The obtained results suggest
that hiPSC-derived mixed neuronal/glial culture could be a valuable in vitro
human model for the establishment of neuronal specific assays in order to link
Nrf2 pathway activation (biomarker of oxidative stress) with additional neuronal
specific readouts that could be applied to in vitro neurotoxicity evaluation.
PMID- 27615061
TI - 4-Hydroxyisophthalic acid from Decalepis hamiltonii rescues the neurobehavioral
deficit in transgenic Drosophila model of taupathies.
AB - Oxidative stress is one of the major etiological factors implicated in
pathogenesis of neurodegenerative diseases. Since neurons are more sensitive to
oxidative damage there is an increasing interest in developing novel antioxidant
therapies, especially herbal preparations due to their safety profile and high
efficiency. In this regard, the neuroprotective potential of a novel antioxidant
compound, 4-hydroxyisophthalic acid (4-HIPA) isolated from aqueous extract of
Decalepis hamiltonii roots was examined using transgenic Drosophila model of
taupathy expressing wild-type and mutant forms of 2N4R isoform of human
microtubule associated protein tau (MAPT). Taupathy model flies showed cognitive
deficits in olfactory memory and deteriorated circadian rhythm of locomotory
activities. Administration of 0.1 mg/ml 4-HIPA, markedly enhanced their olfactory
memory performance and restored circadian rhythmicity of the transgenic flies
locomotory behavior to the normal range. The mechanism of action that underlies 4
HIPA neuroprotection involves enhancement in efficiency of cellular antioxidant
defense system by means of elevation in antioxidant enzyme activities and
attenuation of oxidative stress. The molecule could positively affect the
activity of neurotransmitter enzymes, which in turn enhances neuronal function
and ameliorates the Tau-induced neurobehavioral deficits. Our findings showed
that 4-HIPA can be considered as a suitable therapeutic candidate for drug
development towards treatment of neurodegenerative disorders.
PMID- 27615062
TI - Identification of new single nucleotide polymorphisms affecting total number born
and candidate genes related to ovulation rate in Chinese Erhualian pigs.
AB - The Chinese Erhualian pig has the highest record for litter size in the world.
However, the genetic mechanism of its high prolificacy remains poorly understood.
In our study, large phenotypic variations in litter size were found among
Erhualian sows. Significant differences in total number born (TNB) and corpora
lutea numbers were observed between sows with high and low estimated breeding
values (EBVs) for TNB. To identify single nucleotide polymorphisms (SNPs)
associated with TNB, a selective genomic scan was conducted on 18 sows
representing the top 10% and 18 sows representing the bottom 10% of EBVs of 177
sows using Illumina Porcine SNP60 genotype data. Genome-wide fixation coefficient
(FST ) values were calculated for each SNP between the high- and low-EBV groups.
A total of 154 SNPs were significantly differentiated loci between the two
groups. Of the top 10 highest FST SNPs, rs81399474, rs81400131 and rs81405013 on
SSC8 and rs81434499 and rs81434489 on SSC 12 corresponded to previously reported
QTL for litter size. The other five SNPs, rs81367039 on SSC2, rs80891106 on SSC7,
rs81477883 on SSC12 and rs80938898 and rs80971725 on SSC14, appeared to be novel
QTL for TNB. Significant associations between rs81399474 on SSC8 and TNB were
confirmed in 313 Erhualian sows. Forty genes were identified around the top 10
highest FST SNPs, of which UCHL1, adjacent to rs81399474, and RPS6KB1 and CLTC,
adjacent to rs81434499, have been reported to affect the ovulation rate in pig.
The findings can advance understanding of the genetic variations in litter size
of pigs.
PMID- 27615063
TI - "Usual" Yet Not Uniform Care Limits Our Understanding of Trials of Self
Management Interventions in Heart Failure.
PMID- 27615065
TI - Back to the Future: Circulation Time Revisited.
PMID- 27615064
TI - Prognostic Importance of Novel Oxygen Desaturation Metrics in Patients With Heart
Failure and Central Sleep Apnea.
AB - BACKGROUND: Sleep-disordered breathing, particularly central sleep apnea (CSA),
is highly prevalent in heart failure (HF) and an independent prognostic marker.
We assessed the hypothesis that an increased hypoxemic burden during sleep may
have greater prognostic value than the frequency of apneic and hypopneic
episodes. METHODS AND RESULTS: We prospectively conducted overnight
cardiorespiratory polygraphy on consecutive HF patients referred to our hospital
from 2008 to 2011. We studied CSA defined by an apnea-hypopnea index (AHI) of >=5
events/h with >75% of all events being central in origin. We determined the AHI,
proportion of the sleep time with SpO2 <90% (T90%), and proportion of the
recording time that 4% desaturation events occurred (4%POD). We studied 112 HF
patients with either systolic or diastolic dysfunction. During a follow-up period
of 37 +/- 25 months, 32 patients (29%) died. Nonsurvivors had a higher 4%POD
compared with survivors (11 +/- 6.4% vs 19 +/- 13%; P = .001), but did not differ
significantly from survivors regarding AHI and T90%. An adjusted logistic
regression analysis revealed that the 4%POD was the best independent predictor of
mortality. CONCLUSIONS: The 4%POD, a novel metric for the nocturnal hypoxemic
burden, is an independent prognostic marker in HF patients affected by CSA.
PMID- 27615066
TI - The microbiome of a striped dolphin (Stenella coeruleoalba) stranded in Portugal.
AB - Infectious diseases with epizootic consequences have not been fully studied in
marine mammals. Presently, the unprecedented depth of sequencing, made available
by high-throughput approaches, allows detailed comparisons of the microbiome in
health and disease. This is the first report of the striped dolphin microbiome in
different body sites. Samples from one striped female edematous dolphin were
acquired from a variety of body niches, including the blowhole, oral cavity, oral
mucosa, tongue, stomach, intestines and genital mucosa. Detailed 16S rRNA
analysis of over half a million sequences identified 235 OTUs. Beta diversity
analyses indicated that microbial communities vary in structure and cluster by
sample origin. Pathogenic, Gram-negative, facultative and obligate anaerobic taxa
were significantly detected, including Cetobacterium, Fusobacterium and
Ureaplasma. Phocoenobacter and Arcobacter dominated the oral-type samples, while
Cardiobacteriaceae and Vibrio were associated with the blowhole and
Photobacterium were abundant in the gut. We report for the first time the
association of Epulopiscium with a marine mammal gut. The striped dolphin
microbiota shows variation in structure and diversity according to the organ
type. The high dominance of Gram-negative anaerobic pathogens evidences a
cetacean microbiome affected by human-related bacteria.
PMID- 27615067
TI - Patterns of peripheral cytokine expression during pregnancy in two cohorts and
associations with inflammatory markers in cord blood.
AB - PROBLEM: Maternal inflammation undergoes adaptations during pregnancy, and
excessive inflammation has been associated with adverse outcomes. One mechanism
may be maternal inflammation transmission to the fetal compartment. Links between
maternal pregnancy inflammation and fetal inflammation are poorly characterized.
METHOD: Principal components analysis was used to extract underlying inflammation
components across cytokines (IFN-gamma, IL-10, IL-13, IL-6, IL-8, TNF-alpha) in
two pregnancy cohorts (SPAH N=87, MOMS N=539) assessed during the second and
third trimesters. Links between maternal inflammation over pregnancy and fetal
(cord blood) inflammation were assessed. RESULTS: Substantial cytokine rank-order
stability was observed in both cohorts, beta's range .47-.96, P's <.001. Two
consistent inflammatory components were extracted: a pro-inflammatory (IL-10, IL
6, IL-8, TNF-alpha, IFN-gamma) component and anti-inflammatory (IL-13) component.
Higher maternal pro-inflammatory and lower anti-inflammatory indices during
pregnancy were associated with higher cord blood inflammation, P's>.04.
CONCLUSION: Maternal inflammation indices over pregnancy were associated with
inflammation in cord blood at birth. Results have implications for understanding
pregnancy inflammatory processes and how maternal inflammation may be transmitted
to fetal circulation.
PMID- 27615115
TI - Quantifying cerebrovascular reactivity in anterior and posterior cerebral
circulations during voluntary breath holding.
AB - NEW FINDINGS: What is the central question of this study? We developed and
validated a 'stimulus index' (SI; ratio of end-tidal partial pressures of CO2 and
O2 ) method to quantify cerebrovascular reactivity (CVR) in anterior and
posterior cerebral circulations during breath holding. We aimed to determine
whether the magnitude of CVR is correlated with breath-hold duration. What is the
main finding and its importance? Using the SI method and transcranial Doppler
ultrasound, we found that the magnitude of CVR of the anterior and posterior
cerebral circulations is not positively correlated with physiological or
psychological break-point during end-inspiratory breath holding. Our study
expands the ability to quantify CVR during breath holding and elucidates factors
that affect break-point. The central respiratory chemoreflex contributes to blood
gas homeostasis, particularly in response to accumulation of brainstem CO2 .
Cerebrovascular reactivity (CVR) affects chemoreceptor stimulation inversely
through CO2 washout from brainstem tissue. Voluntary breath holding imposes
alterations in blood gases, eliciting respiratory chemoreflexes, potentially
contributing to breath-hold duration (i.e. break-point). However, the effects of
cerebrovascular reactivity on break-point have yet to be determined. We tested
the hypothesis that the magnitude of CVR contributes directly to breath-hold
duration in 23 healthy human participants. We developed and validated a
cerebrovascular stimulus index methodology [SI; ratio of end-tidal partial
pressures of CO2 and O2 (P ET ,CO2/P ET ,O2)] to quantify CVR by correlating
measured and interpolated values of P ET ,CO2 (r = 0.95, P < 0.0001), P ET ,O2 (r
= 0.98, P < 0.0001) and SI (r = 0.94, P < 0.0001) during rebreathing. Using
transcranial Doppler ultrasound, we then quantified the CVR of the middle (MCAv)
and posterior (PCAv) cerebral arteries by plotting cerebral blood velocity
against interpolated SI during a maximal end-inspiratory breath hold. The MCAv
CVR magnitude was larger than PCAv (P = 0.001; +70%) during breath holding. We
then correlated MCAv and PCAv CVR with the physiological (involuntary
diaphragmatic contractions) and psychological (end-point) break-point, within
individuals. There were significant inverse but modest relationships between both
MCAv and PCAv CVR and both physiological and psychological break-points (r <
0.53, P < 0.03). However, these relationships were absent when MCAv and PCAv
cerebrovascular conductance reactivity was correlated with both physiological and
psychological break-points (r > -0.42; P > 0.06). Although central chemoreceptor
activation is likely to be contributing to break-point, our data suggest that CVR
mediated CO2 washout from central chemoreceptors plays no role in determining
break-point, probably because of a reduced arterial-to-tissue CO2 gradient during
breath holding.
PMID- 27615116
TI - Percutaneous Nephrolithotomy in Immunocompromised Patients: Outcomes from a
Matched Case-Control Study.
AB - OBJECTIVE: To compare the outcomes of percutaneous nephrolithotomy (PCNL) in
immunocompromised patients with those of PCNL in healthy population. PATIENTS AND
METHODS: A matched case-control study was performed from January 2009 through
December 2014 using our prospectively collected kidney stone database. Patients
with positive serology to human immunodeficiency virus (HIV), hepatitis C
(cellular immune dysfunction), and patients on high dose of immunosuppressive
drugs for treatment of autoimmune diseases composed the case group. Control group
included patients with kidney stones and no other comorbidity. Patients were
randomly matched based on Guy's score as a surrogate of case complexity. RESULTS:
Sixty-two patients were enrolled in this study, 21 cases and 42 controls. There
were no significant differences in age, gender, and body mass index between
groups. Regarding PCNL technique, there were no differences in patient
positioning, number of accesses, and operative time. Complication rate was higher
in the case group (38.1% vs 14.3%; p = 0.032); however, major complications,
defined by Clavien score >=3, were not statistically different (4.8% vs 2.4%; p =
0.611). There was a tendency of more postoperative urinary tract infection in the
case group (19% vs 4.8%; p = 0.069). Mean decrease in hemoglobin level (3.3 vs
2.4 mg/dL; p = 0.037) and blood transfusion rate (23.8% vs 4.8%; p = 0.036) was
significantly higher in the case group. Immunocompromised patients had a 2.8-fold
increased risk of complications (odds ratio [OR] = 2.0, 95% confidence interval
[CI] 1.01, 7.74) and a 5.8-fold increased risk of blood transfusion (OR = 5.8,
95% CI 1.29, 26.55). There were no differences in stone-free rate, nephrostomy
tube time, and length of hospital stay. CONCLUSION: Immunocompromised patients
are at higher risk for complications such as bleeding after PCNL.
PMID- 27615117
TI - Reticular Chemistry at Its Best: Directed Assembly of Hexagonal Building Units
into the Awaited Metal-Organic Framework with the Intricate Polybenzene Topology,
pbz-MOF.
AB - The ability to direct the assembly of hexagonal building units offers great
prospective to construct the awaited and looked-for hypothetical polybenzene
(pbz) or "cubic graphite" structure, described 70 years ago. Here, we demonstrate
the successful use of reticular chemistry as an appropriate strategy for the
design and deliberate construction of a zirconium-based metal-organic framework
(MOF) with the intricate pbz underlying net topology. The judicious selection of
the perquisite hexagonal building units, six connected organic and inorganic
building blocks, allowed the formation of the pbz-MOF-1, the first example of a
Zr(IV)-based MOF with pbz topology. Prominently, pbz-MOF-1 is highly porous, with
associated pore size and pore volume of 13 A and 0.99 cm3 g-1, respectively, and
offers high gravimetric and volumetric methane storage capacities (0.23 g g-1 and
210.4 cm3 (STP) cm-3 at 80 bar). Notably, the pbz-MOF-1 pore system permits the
attainment of one of the highest CH4 adsorbed phase density enhancements at high
pressures (0.15 and 0.21 g cm-3 at 35 and 65 bar, respectively) as compared to
benchmark microporous MOFs.
PMID- 27615119
TI - Orchestrating care through the fast-track perspective: A qualitative content
analysis of the provision of individualised nursing care in orthopaedic fast
track programmes.
AB - The lack of individualised care in orthopaedic regimes is often explained by the
extended use of patient pathways and clinical guidelines. The aim of this study
was to illuminate orthopaedic nurses' perceptions and experiences of providing
individual nursing care for older patients in standardised fast-track programmes
after total hip or knee replacement. Ten semi-structured interviews were
conducted with orthopaedic nurses in orthopaedic wards at three Danish hospitals
between April and June of 2015. Data were analysed using manifest and latent
content analysis according to Graneheim and Lundman. The main theme of the
overall interpretation was Orchestrating care through the fast-track perspective,
accompanied by three sub-themes: Identifying and legitimising relevant individual
care in the fast-track programme, Struggling to fit all patients in the fast
track programme and Justifying individualised care-related actions in the fast
track programme. The study concluded that, even though the nurses struggled to
comply with the programme, they still found themselves compromising their nursing
care and ethics to follow the standardised regime. There is a need to establish
more specific inclusion criteria to maintain the effective elements in the
programme and to facilitate nurses' opportunities to offer individual care,
thereby ensuring that fragile patients have access to other possibilities.
PMID- 27615118
TI - Zein nanoparticles for oral delivery of quercetin: Pharmacokinetic studies and
preventive anti-inflammatory effects in a mouse model of endotoxemia.
AB - Zein nanoparticles were evaluated as nanocarriers to promote the oral
bioavailability of quercetin and, thus, improve its anti-inflammatory effect on a
mouse model of induced endotoxemia. For this purpose, the flavonoid and 2
hydroxypropyl-beta-cyclodextrin were encapsulated in zein nanoparticles. The
resulting nanoparticles displayed a mean size of about 300nm and the payload was
calculated to be close to 70MUg/mg nanoparticle. The release of quercetin from
zein nanoparticles followed a zero-order kinetic. After oral administration,
nanoparticles provided high and sustained levels of quercetin in plasma and the
relative oral bioavailability was calculated to be approx. 60%. Animals treated
with quercetin-loaded nanoparticles (1 dose every two days; 1week) presented
endotoxic symptoms less severe than those observed in animals treated with the
oral solution of the flavonoid (1 dose every day; 1week). This was further
corroborated by the significantly low circulating TNF-alpha in the quercetin
loaded nanoparticles treated mice.
PMID- 27615120
TI - Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in
Cats with or without the A31P Mutation in MYBPC3.
AB - BACKGROUND: Clopidogrel is commonly prescribed to cats with perceived increased
risk of thromboembolic events, but little information exists regarding its
antiplatelet effects. OBJECTIVE: To determine effects of clopidogrel on platelet
responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A
secondary aim was to characterize variability in feline platelet responses to
clopidogrel. ANIMALS: Fourteen healthy cats from a Maine Coon/outbred mixed
Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6
wild-type cats without the A31P mutation. METHODS: Ex vivo study. All cats
received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel
treatment, adenosine diphosphate (ADP)-induced P-selectin expression was
evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical
aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were
measured by Western blot analysis. RESULTS: Platelet activation from cats with
the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55)
to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated
ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE1
treated platelets had a similar level of pVASP as PGE1 -treated platelets after
clopidogrel treatment. Clopidogrel administration resulted in significantly lower
ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13
cats were nonresponders based on OA and flow cytometry. CONCLUSION AND CLINICAL
IMPORTANCE: Clopidogrel is effective at attenuating platelet activation and
aggregation in some cats. Cats with A31P mutation had increased platelet
activation relative to the variable response seen in wild-type cats.
PMID- 27615121
TI - Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia
compared to normotensive pregnant women.
AB - PURPOSE: To investigate the cerebrospinal fluid (CSF) proteome of patients with
preeclampsia (PE) and normotensive pregnant women, in order to provide a better
understanding of brain involvement in PE. EXPERIMENTAL DESIGN: Ninety-eight CSF
samples (43 women with PE and 55 normotensive controls) were analyzed by LC-MS/MS
proteome profiling. CSF was obtained during the spinal puncture before caesarean
delivery. RESULTS: Eight proteins were higher abundant and 17 proteins were lower
abundant in patients with PE. The most significantly differentially abundant
protein was protein AMBP (alpha-1-microglobulin/bikunin precursor). This finding
was validated by performing an ELISA experiment (p = 0.002). CONCLUSIONS AND
CLINICAL RELEVANCE: The current study showed a clear difference between the
protein profiles of CSF from patients with PE and normotensive pregnant women.
Protein AMBP is a precursor of a heme-binding protein that counteracts the
damaging effects of free hemoglobin, which may be related to the presence of free
hemoglobin in CSF. Protein levels showed correlations with clinical symptoms
during pregnancy and postpartum. To our knowledge, this is the first LC-MS/MS
proteome profiling study on a unique set of CSF samples from (severe)
preeclamptic patients and normotensive pregnant women.
PMID- 27615123
TI - Nutritional Supplement Use by Dutch Elite and Sub-Elite Athletes: Does Receiving
Dietary Counseling Make a Difference?
AB - The use of nutritional supplements is highly prevalent among athletes. In this
cross-sectional study, we assessed the prevalence of nutritional supplement use
by a large group of Dutch competitive athletes in relation to dietary counseling.
A total of 778 athletes (407 males and 371 females) completed a web-based
questionnaire about the use of nutritional supplements. Log-binomial regression
models were applied to estimate crude and adjusted prevalence ratios (PR) for the
use of individual nutritional supplements in athletes receiving dietary
counseling as compared with athletes not receiving dietary counseling. Of the
athletes, 97.2% had used nutritional supplements at some time during their sports
career, whereas 84.7% indicated having used supplements during the last 4 weeks.
The top ranked supplements used over the last 4 weeks from dietary supplements,
sport nutrition products and ergogenic supplements were multivitamin and mineral
preparations (42.9%), isotonic sports drinks (44.1%) and caffeine (13.0%). After
adjustment for elite status, age, and weekly exercise duration, dietary
counseling was associated with a higher prevalence of the use of vitamin D,
recovery drinks, energy bars, isotonic drinks with protein, dextrose, beta
alanine, and sodium bicarbonate. In contrast, dietary counseling was inversely
associated with the use of combivitamins, calcium, vitamin E, vitamin B2,
retinol, energy drinks and BCAA and other amino acids. In conclusion, almost all
athletes had used nutritional supplements at some time during their athletic
career. Receiving dietary counseling seemed to result in better-informed choices
with respect to the use of nutritional supplements related to performance,
recovery, and health.
PMID- 27615125
TI - Unidirectional perfect absorber.
AB - This study proposes a unidirectional perfect absorber (UPA), which we realized
with a two-arm Aharonov-Bohm interferometer, that consists of a dissipative
resonator side-coupled to a uniform resonator array. The UPA has reflection-less
full absorption on one direction, and reflectionless full transmission on the
other, with an appropriate magnetic flux and coupling, detuning, and loss of the
side-coupled resonator. The magnetic flux controls the transmission, the left
transmission is larger for magnetic flux less than one-half flux quantum; and the
right transmission is larger for magnetic flux between one-half and one flux
quantum. Besides, a perfect absorber (PA) can be realized based on the UPA, in
which light waves from both sides, with arbitrary superposition of the ampli-
tude and phase, are perfectly absorbed. The UPA is expected to be useful in the
design of novel optical devices.
PMID- 27615124
TI - The Mechanism of Hsp90 ATPase Stimulation by Aha1.
AB - Hsp90 is a dimeric molecular chaperone responsible for the folding, maturation,
and activation of hundreds of substrate proteins called 'clients'. Numerous co
chaperone proteins regulate progression through the ATP-dependent client
activation cycle. The most potent stimulator of the Hsp90 ATPase activity is the
co-chaperone Aha1p. Only one molecule of Aha1p is required to fully stimulate the
Hsp90 dimer despite the existence of two, presumably identical, binding sites for
this regulator. Using ATPase assays with Hsp90 heterodimers, we find that Aha1p
stimulates ATPase activity by a three-step mechanism via the catalytic loop in
the middle domain of Hsp90. Binding of the Aha1p N domain to the Hsp90 middle
domain exerts a small stimulatory effect but also drives a separate
conformational rearrangement in the Hsp90 N domains. This second event drives a
rearrangement in the N domain of the opposite subunit and is required for the
stimulatory action of the Aha1p C domain. Furthermore, the second event can be
blocked by a mutation in one subunit of the Hsp90 dimer but not the other. This
work provides a foundation for understanding how post-translational modifications
regulate co-chaperone engagement with the Hsp90 dimer.
PMID- 27615126
TI - Cell fate conversion-from the viewpoint of small molecules and lineage
specifiers.
AB - Mammalian development was generally considered a naturally unidirectional and
irreversible process. However, pioneering work of recent decades has highlighted
the plasticity of mammalian cells and implied the possibilities of manipulating
cell fate in vitro. Pluripotent stem cells, which hold great potential for
regenerative medicine, have been shown to be reprogrammed from differentiated
cells either by somatic cell nuclear transfer or by ectopic expression of
pluripotency factors. Nevertheless, it remained unknown whether the reprogramming
could be accomplished without pluripotency genes. Recent studies show that
lineage specifiers play an important role in orchestrating the process of
restoring pluripotency by replacing pluripotency-associated transcription
factors. Moreover, a combination of small molecules enables the acquisition of
pluripotency from somatic cells without any transgenes, offering a tractable
platform to precisely dissect the induction and maintenance of cell identity.
Here, we will discuss recent scientific advances regarding the cell fate
conversion mediated by small molecules or lineage specifiers, especially in the
chemically induced somatic cell reprogramming process, and will provide new
insights into the intermediate plastic state and "seesaw model" established by
chemical approaches during reprogramming.
PMID- 27615127
TI - Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse
and man.
AB - During embryonic development, endocrine cells of the pancreas are specified from
multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is
critical for this development and it has been shown that all endocrine cells of
the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough
understanding of the role of NEUROG3 during development, directed differentiation
of pluripotent stem cells and in models of cellular reprogramming, will guide
future efforts directed at finding novel sources of beta-cells for cell
replacement therapies. In this article, we review the expression and function of
NEUROG3 in both mouse and human and present the further characterization of a
monoclonal antibody directed against NEUROG3. This antibody has been previously
been used for detection of both mouse and human NEUROG3. However, our results
suggest that the epitope recognized by this antibody is specific to mouse
NEUROG3. Thus, we have also generated a monoclonal antibody specifically
recognizing human NEUROG3 and present the characterization of this antibody here.
Together, these antibodies will provide useful tools for future studies of
NEUROG3 expression, and the data presented in this article suggest that recently
described expression patterns of NEUROG3 in human foetal and adult pancreas
should be re-examined.
PMID- 27615128
TI - The role of hepatocyte nuclear factor 1beta in disease and development.
AB - Heterozygous mutations in the gene that encodes the transcription factor
hepatocyte nuclear factor 1beta (HNF1B) result in a multi-system disorder. HNF1B
was initially discovered as a monogenic diabetes gene; however, renal cysts are
the most frequently detected feature. Other clinical features include pancreatic
hypoplasia and exocrine insufficiency, genital tract malformations, abnormal
liver function, cholestasis and early-onset gout. Heterozygous mutations and
complete gene deletions in HNF1B each account for approximately 50% of all cases
of HNF1B-associated disease and may show autosomal dominant inheritance or arise
spontaneously. There is no clear genotype-phenotype correlation indicating that
haploinsufficiency is the main disease mechanism. Data from animal models suggest
that HNF1B is essential for several stages of pancreas and liver development.
However, mice with heterozygous mutations in HNF1B show no phenotype in contrast
to the phenotype seen in humans. This suggests that mouse models do not fully
replicate the features of human disease and complementary studies in human
systems are necessary to determine the molecular mechanisms underlying HNF1B
associated disease. This review discusses the role of HNF1B in human and murine
pancreas and liver development, summarizes the disease phenotypes and identifies
areas for future investigations in HNF1B-associated diabetes and liver disease.
PMID- 27615122
TI - Mechanisms of Photoreceptor Patterning in Vertebrates and Invertebrates.
AB - Across the animal kingdom, visual systems have evolved to be uniquely suited to
the environments and behavioral patterns of different species. Visual acuity and
color perception depend on the distribution of photoreceptor (PR) subtypes within
the retina. Retinal mosaics can be organized into three broad categories:
stochastic/regionalized, regionalized, and ordered. We describe here the retinal
mosaics of flies, zebrafish, chickens, mice, and humans, and the gene regulatory
networks controlling proper PR specification in each. By drawing parallels in eye
development between these divergent species, we identify a set of conserved
organizing principles and transcriptional networks that govern PR subtype
differentiation.
PMID- 27615130
TI - Role of long non-coding RNAs in the determination of beta-cell identity.
AB - Pancreatic beta-cells are highly specialized cells committed to secrete insulin
in response to changes in the level of nutrients, hormones and neurotransmitters.
Chronic exposure to elevated concentrations of glucose, fatty acids or
inflammatory mediators can result in modifications in beta-cell gene expression
that alter their functional properties. This can lead to the release of
insufficient amount of insulin to cover the organism's needs, and thus to the
development of diabetes mellitus. Although most of the studies carried out in the
last decades to elucidate the causes of beta-cell dysfunction under disease
conditions have focused on protein-coding genes, we now know that insulin
secreting cells also contain thousands of molecules of RNA that do not encode
polypeptides but play key roles in the acquisition and maintenance of a highly
differentiated state. In this review, we will highlight the involvement of long
non-coding RNAs (lncRNAs), a particular class of non-coding transcripts, in the
differentiation of beta-cells and in the regulation of their specialized tasks.
We will also discuss the crosstalk between the activities of lncRNAs and
microRNAs and present the emerging evidence of a potential contribution of
particular lncRNAs to the development of both type 1 and type 2 diabetes.
PMID- 27615129
TI - Three-dimensional pancreas organogenesis models.
AB - A rediscovery of three-dimensional culture has led to the development of organ
biogenesis, homeostasis and disease models applicable to human tissues. The so
called organoids that have recently flourished serve as valuable models bridging
between cell lines or primary cells grown on the bottom of culture plates and
experiments performed in vivo. Though not recapitulating all aspects of organ
physiology, the miniature organs generated in a dish are useful models emerging
for the pancreas, starting from embryonic progenitors, adult cells, tumour cells
and stem cells. This review focusses on the currently available systems and their
relevance to the study of the pancreas, of beta-cells and of several pancreatic
diseases including diabetes. We discuss the expected future developments for
studying human pancreas development and function, for developing diabetes models
and for producing therapeutic cells.
PMID- 27615131
TI - Shaping and preserving beta-cell identity with microRNAs.
AB - The highly sophisticated identity of pancreatic beta-cells is geared to
accomplish its unique feat of providing insulin for organismal glucose and lipid
homeostasis. This requires a particular and streamlined fuel metabolism which
defines mature beta-cells as glucose sensors linked to an insulin exocytosis
machinery. The establishment of an appropriate beta-cell mass and function during
development as well as the maintenance of their identity throughout life are
necessary for energy homeostasis. The small non-coding RNAs, microRNAs (miRNAs),
are now well-recognized regulators of gene transcripts, which in general are
negatively affected by them. Convincing evidence exists to view miRNAs as major
actors in beta-cell development and function, suggesting an important role for
them in the distinctive beta-cell 'identity card'. Here, we summarize key
features that associate miRNAs and the establishment of the appropriate beta-cell
identity and its necessary maintenance during their 'long life'.
PMID- 27615132
TI - Effects of ageing and senescence on pancreatic beta-cell function.
AB - Ageing is generally associated with deterioration of organ function and
regenerative potential. In the case of pancreatic beta-cells, an age-related
decline in proliferative potential is well documented, and was proposed to
contribute to the increased prevalence of type 2 diabetes in the elderly. The
effects of ageing on beta-cell function, namely glucose-stimulated insulin
secretion (GSIS), have not been studied as extensively. Recent work revealed
that, surprisingly, beta-cells of mature mice and humans secrete more insulin
than young beta-cells in response to high glucose concentrations, potentially
serving to counteract age-related peripheral insulin resistance. This functional
change appears to be orchestrated by p16(Ink4A) -driven cellular senescence and
downstream remodelling of chromatin structure and DNA methylation, enhancing the
expression of genes controlling beta-cell function. We propose that activation of
the cellular senescence program drives life-long functional maturation of beta
cells, due to beta-cell hypertrophy, enhanced glucose uptake and more efficient
mitochondrial metabolism, in parallel to locking these cells in a non-replicative
state. We speculate that the beneficial aspects of this process can be harnessed
to enhance GSIS. Other age-related mechanisms, which are currently poorly
understood, act to increase basal insulin secretion levels also in low glucose
conditions. This leads to an overall reduction in the amplitude of insulin
secretion between low and high glucose at old age, which may contribute to a
deterioration in metabolic control.
PMID- 27615133
TI - beta-Cell adaptation in pregnancy.
AB - Pregnancy in placental mammals places unique demands on the insulin-producing
beta-cells in the pancreatic islets of Langerhans. The pancreas anticipates the
increase in insulin resistance that occurs late in pregnancy by increasing beta
cell numbers and function earlier in pregnancy. In rodents, this beta-cell
expansion depends on secreted placental lactogens that signal through the
prolactin receptor. Then at the end of pregnancy, the beta-cell population
contracts back to its pre-pregnancy size. In the current review, we focus on how
glucose metabolism changes during pregnancy, how beta-cells anticipate these
changes through their response to lactogens and what molecular mechanisms guide
the adaptive compensation. In addition, we summarize current knowledge of beta
cell adaptation during human pregnancy and what happens when adaptation fails and
gestational diabetes ensues. A better understanding of human beta-cell adaptation
to pregnancy would benefit efforts to predict, prevent and treat gestational
diabetes.
PMID- 27615134
TI - Novel factors modulating human beta-cell proliferation.
AB - beta-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a
progressive loss of beta-cells, and an understanding of the cellular mechanism(s)
that regulate beta-cell mass will enable approaches to enhance hormone secretion.
It is becoming increasingly recognized that enhancement of human beta-cell
proliferation is one potential approach to restore beta-cell mass to prevent
and/or cure type 1 and type 2 diabetes. While several reports describe the
factor(s) that enhance beta-cell replication in animal models or cell lines,
promoting effective human beta-cell proliferation continues to be a challenge in
the field. In this review, we discuss recent studies reporting successful human
beta-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine
and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3beta and DYRK1A
inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK)
inhibitors; and SerpinB1, a protease inhibitor. These studies provide important
examples of proteins and pathways that may prove useful for designing therapeutic
strategies to counter the different forms of human diabetes.
PMID- 27615135
TI - Mechanisms of beta-cell functional adaptation to changes in workload.
AB - Insulin secretion must be tightly coupled to nutritional state to maintain blood
glucose homeostasis. To this end, pancreatic beta-cells sense and respond to
changes in metabolic conditions, thereby anticipating insulin demands for a given
physiological context. This is achieved in part through adjustments of nutrient
metabolism, which is controlled at several levels including allosteric
regulation, post-translational modifications, and altered expression of metabolic
enzymes. In this review, we discuss mechanisms of beta-cell metabolic and
functional adaptation in the context of two physiological states that alter
glucose-stimulated insulin secretion: fasting and insulin resistance. We review
current knowledge of metabolic changes that occur in the beta-cell during
adaptation and specifically discuss transcriptional mechanisms that underlie beta
cell adaptation. A more comprehensive understanding of how beta-cells adapt to
changes in nutrient state could identify mechanisms to be co-opted for
therapeutically modulating insulin secretion in metabolic disease.
PMID- 27615137
TI - Mechanisms of adult human beta-cell in vitro dedifferentiation and
redifferentiation.
AB - Recent studies in animal models and human pathological specimens suggest the
involvement of beta-cell dedifferentiation in beta-cell dysfunction associated
with type 2 diabetes. Dedifferentiated beta-cells may be exploited for endogenous
renewal of the beta-cell mass. However, studying human beta-cell
dedifferentiation in diabetes presents major difficulties. We have analysed
mechanisms involved in human beta-cell dedifferentiation in vitro, under
conditions that allow cell proliferation. Although there are important
differences between the two cellular environments, beta-cell dedifferentiation in
the two conditions is likely to share a number of common pathways. Insights from
the in vitro studies may lead to development of approaches for redifferentiation
of endogenous dedifferentiated beta-cells.
PMID- 27615136
TI - Stress-induced adaptive islet cell identity changes.
AB - The different forms of diabetes mellitus differ in their pathogenesis but,
ultimately, they are all characterized by progressive islet beta-cell loss.
Restoring the beta-cell mass is therefore a major goal for future therapeutic
approaches. The number of beta-cells found at birth is determined by
proliferation and differentiation of pancreatic progenitor cells, and it has been
considered to remain mostly unchanged throughout adult life. Recent studies in
mice have revealed an unexpected plasticity in islet endocrine cells in response
to stress; under certain conditions, islet non-beta-cells have the potential to
reprogram into insulin producers, thus contributing to restore the beta-cell
mass. Here, we discuss the latest findings on pancreas and islet cell plasticity
upon physiological, pathological and experimental conditions of stress.
Understanding the mechanisms involved in cell reprogramming in these models will
allow the development of new strategies for the treatment of diabetes, by
exploiting the intrinsic regeneration capacity of the pancreas.
PMID- 27615138
TI - beta-Cell dysfunction in diabetes: a crisis of identity?
AB - Type 2 diabetes is characterized by insulin resistance and a progressive loss of
beta-cell function induced by a combination of both beta-cell loss and impaired
insulin secretion from remaining beta-cells. Here, we review the fate of the beta
cell under chronic hyperglycaemic conditions with regard to beta-cell mass, gene
expression, hormone content, secretory capacity and the ability to de- or
transdifferentiate into other cell types. We compare data from various in vivo
and in vitro models of diabetes with a novel mouse model of inducible, reversible
hyperglycaemia (betaV59M mice). We suggest that insulin staining using standard
histological methods may not always provide an accurate estimation of beta-cell
mass or number. We consider how beta-cell identity is best defined, and whether
expression of transcription factors normally found in islet progenitor cells, or
in alpha-cells, implies that mature beta-cells have undergone dedifferentiation
or transdifferentiation. We propose that even in long-standing diabetes, beta
cells predominantly remain beta-cells-but not as we know them.
PMID- 27615140
TI - When beta-cells fail: lessons from dedifferentiation.
AB - Diabetes is caused by a combination of impaired responsiveness to insulin and
reduced production of insulin by the pancreas. Until recently, the decline of
insulin production had been ascribed to beta-cell death. But recent research has
shown that beta-cells do not die in diabetes, but undergo a silencing process,
termed "dedifferentiation." The main implication of this discovery is that beta
cells can be revived by appropriate treatments. We have shown that mitochondrial
abnormalities are a key step in the progression of beta-cell dysfunction towards
dedifferentiation. In normal beta-cells, mitochondria generate energy required to
sustain insulin production and its finely timed release in response to the body's
nutritional status. A normal beta-cell can adapt its mitochondrial fuel source
based on substrate availability, a concept known as "metabolic flexibility." This
capability is the first casualty in the progress of beta-cell failure. beta-Cells
lose the ability to select the right fuel for mitochondrial energy production.
Mitochondria become overloaded, and accumulate by-products derived from
incomplete fuel utilization. Energy production stalls, and insulin production
drops, setting the stage for dedifferentiation. The ultimate goal of these
investigations is to explore novel treatment paradigms that will benefit people
with diabetes.
PMID- 27615139
TI - Pancreatic beta-cell identity in diabetes.
AB - Recovery of functional beta-cell mass continues to be an ongoing challenge in
treating diabetes. Initial work studying beta-cells suggested apoptotic beta-cell
death as a main contributor for the loss of beta-cell mass in diabetes.
Restoration of beta-cells either by transplant or stimulating proliferation of
remaining beta-cells or precursors would then logically be a viable therapeutic
option for diabetes. However, recent work has highlighted the inherent beta-cell
plasticity and the critical role of loss of beta-cell identity in diabetes, and
has suggested that beta-cells fail to maintain a fully differentiated glucose
responsive and drug-responsive state, particularly in diabetic individuals with
poorly controlled, long-lasting periods of hyperglycaemia. Understanding the
underlying mechanisms of loss of beta-cell identity and conversion in other cell
types, as well as how to regain their mature differentiated functional state, is
critical to develop novel therapeutic strategies to prevent or reverse these
processes. In this review, we discuss the role of plasticity and loss of beta
cell identity in diabetes, the current understanding of mechanisms involved in
altering this mature functional beta-cell state and potential progresses to
identify novel therapeutic targets providing better opportunities for slowing or
preventing diabetes progression.
PMID- 27615142
TI - Mass production of functional human pancreatic beta-cells: why and how?
AB - Diabetes (either type 1 or type 2) is due to insufficient functional beta-cell
mass. Research has, therefore, aimed to discover new ways to maintain or increase
either beta-cell mass or function. For this purpose, rodents have mainly been
used as model systems and a large number of discoveries have been made.
Meanwhile, although we have learned that rodent models represent powerful systems
to model beta-cell development, function and destruction, we realize that there
are limitations when attempting to transfer the data to what is occurring in
humans. Indeed, while human beta-cells share many similarities with rodent beta
cells, they also differ on a number of important parameters. In this context,
developing ways to study human beta-cell development, function and death
represents an important challenge. This review will describe recent data on the
development and use of convenient sources of human beta-cells that should be
useful tools to discover new ways to modulate functional beta-cell mass in
humans.
PMID- 27615141
TI - Impact of Pdx1-associated chromatin modifiers on islet beta-cells.
AB - Diabetes mellitus arises from insufficient insulin secretion from pancreatic
islet beta-cells. In type 2 diabetes (T2D), beta-cell dysfunction is associated
with inactivation and/or loss of transcription factor (TF) activity, including
Pdx1. Notably, this particular TF is viewed as a master regulator of pancreas
development and islet beta-cell formation, identity and function. TFs, like Pdx1,
recruit coregulators to transduce activating and/or repressing signals to the
general transcriptional machinery for controlling gene expression, including
modifiers of DNA, histones and nucleosome architecture. These coregulators impart
a secondary layer of control that can be exploited to modulate TF activity. In
this review, we describe Pdx1-recruited coregulators that impact chromatin
structure, consequently influencing normal beta-cell function and likely Pdx1
activity in pathophysiological settings.
PMID- 27615143
TI - beta-Cell replacement as a treatment for type 1 diabetes: an overview of possible
cell sources and current axes of research.
AB - To efficiently treat type 1 diabetes, exogenous insulin injections currently
represent the main approach to counter chronic hyperglycaemia. Unfortunately,
such a therapeutic approach does not allow for perfectly maintained glucose
homeostasis and, in time, cardiovascular complications may arise. Therefore,
seeking alternative/improved treatments has become a major health concern as an
increasing proportion of type 2 diabetes patients also require insulin
supplementation. Towards this goal, numerous laboratories have focused their
research on beta-cell replacement therapies. Herein, we will review the current
state of this research area and describe the cell sources that could potentially
be used to replenish the depleted beta-cell mass in diabetic patients.
PMID- 27615144
TI - Making beta(-like)-cells from exocrine pancreas.
AB - Creating an abundant source of beta(-like)-cells has been a major goal in
diabetes research for many decades. The concept of cell plasticity has inspired
many strategies towards regenerative medicine, but its successes have been
limited until very recently. Today, most cell types in the pancreas are
considered candidates for the generation of beta(-like)-cells through
transdifferentiation. While beta(-like)-cells that are in vitro differentiated
from human embryonic stem cells are already being grafted in patients, beta(
like)-cells generated by transdifferentiation are not yet ready for clinical
application. These cells would however offer several advantages over the current
beta(-like)-cells generated by directed differentiation, especially concerning
safety issues. In addition, perfect control of the transdifferentiation
efficiency would through targeted drug delivery support a non-invasive cell
therapy for diabetes. Lastly, focusing on the exocrine pancreas as prime
candidate makes sense in view of their abundance and high plasticity. Keeping
these hopeful perspectives in mind, it is worth to continue focused research on
the mechanisms that control transdifferentiation from pancreas exocrine to beta
cells.
PMID- 27615145
TI - Assessing the viability of long-acting beta2-agonists in paediatric asthma
patients: a pharmacokinetic/pharmacodynamic perspective.
AB - INTRODUCTION: Long-acting beta2-agonists (LABAs) combined with inhaled
corticosteroids (ICSs) are still commonly prescribed to asthmatic children.
Unfortunately, pediatric LABA use is based primarily on data from adults, despite
the fact that children are not simply small adults and the magnitude of changes
in dose exposure and/or exposure response may not be solely reflected by
differences in body weight. Areas covered: The differences in pharmacokinetics
(PK) and pharmacodynamics (PD) of LABAs are described and discussed with
reference children and adults. Expert opinion: Data on the PK behavior of LABAs
is very limited and there is almost no data on once-daily LABAs available in the
pediatric population. We do not believe that this is due to a fundamental lack of
information because therapeutic response and adverse effects are more useful for
the optimization of beta2-agonist treatment than measurement of plasma drug
concentrations per se. Nevertheless, population PK-PD studies in children are
needed according to the European rules in order to define rational, patient
tailored dosing schemes. Population PK-PD modeling and simulation using non
linear mixed effect modeling should be considered as the preferred tool to
develop effective and safe dosing regimens for children because they present an
opportunity to analyze sparse and unbalanced datasets, thereby minimizing the
burden for each child.
PMID- 27615146
TI - Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney
Disease: A Population-Based Longitudinal Study.
AB - BACKGROUND: No large epidemiological study has been conducted to investigate the
interaction and joint effects of periodontal pocket depth and hyperglycemia on
progression of chronic kidney disease in patients with periodontal diseases.
METHODS: Periodontal pocket depth was utilized for the grading severity of
periodontal disease in 2831 patients from January 2002 to June 2013. Progression
of chronic kidney disease was defined as progression of color intensity in
glomerular filtration rate and albuminuria grid of updated Kidney Disease
Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR)
in various models were presented across different levels of periodontal pocket
depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms.
RESULTS: During 7621 person-years of follow-up, periodontal pocket depth and
HbA1C levels were robustly associated with incremental risks for progression of
chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for
periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%,
respectively). The interaction between periodontal pocket depth and HbA1C on
progression of chronic kidney disease was strong (P <.01). Patients with higher
periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk
(aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket
depth <=3.8 mm and HbA1C <=6%). CONCLUSION: Our study identified combined
periodontal pocket depth and HbA1C as a valuable predictor of progression of
chronic kidney disease in patients with periodontal diseases. While considering
the interaction between periodontal diseases and hyperglycemia, periodontal
survey and optimizing glycemic control are warranted to minimize the risk of
worsening renal function.
PMID- 27615147
TI - Prekallikrein deficiency in a 15-year-old boy with Meniere's disease: a case
report.
AB - Congenital prekallikrein deficiency is a rare disorder in which there is an in
vitro clotting defect despite absence of bleeding or thrombotic tendency. In this
report, a 15-year-old boy with an unexpected markedly prolonged activated partial
thrombin time, a normal prothrombin time, and without personal nor familial
history of bleeding or thrombosis is presented. Laboratory investigation revealed
a severe prekallikrein deficiency. This case highlights the importance of
following a diagnostic algorithm to establish the correct diagnosis. Moreover, by
selecting appropriate laboratory tests, unnecessary and repeatedly testing can be
avoided.
PMID- 27615148
TI - Interaction between isoprene and ozone fluxes in a poplar plantation and its
impact on air quality at the European level.
AB - The emission of isoprene and other biogenic volatile organic compounds from
vegetation plays an important role in tropospheric ozone (O3) formation. The
potentially large expansion of isoprene emitting species (e.g., poplars) for
bioenergy production might, therefore, impact tropospheric O3 formation. Using
the eddy covariance technique we have simultaneously measured fluxes isoprene, O3
and of CO2 from a poplar (Populus) plantation grown for bioenergy production. We
used the chemistry transport model LOTOS-EUROS to scale-up the isoprene emissions
associated with the existing poplar plantations in Europe, and we assessed the
impact of isoprene fluxes on ground level O3 concentrations. Our findings suggest
that isoprene emissions from existing poplar-for-bioenergy plantations do not
significantly affect the ground level of O3 concentration. Indeed the overall
land in Europe covered with poplar plantations has not significantly changed over
the last two decades despite policy incentives to produce bioenergy crops. The
current surface area of isoprene emitting poplars-for-bioenergy remains too
limited to significantly enhance O3 concentrations and thus to be considered a
potential threat for air quality and human health.
PMID- 27615149
TI - Analysis and comparison of lignin peroxidases between fungi and bacteria using
three different modes of Chou's general pseudo amino acid composition.
AB - Lignin peroxidases (LiPs) are important enzymes in the degradation process of
lignin which are presented in different species of fungi and bacteria. In the
present study, sequence and structure-based properties of LPs in fungi and
bacteria are compared. These properties include pseudo amino acid composition
(PseAAC), physicochemical properties and the secondary structure. Autodock 4 has
been used for docking between LiPs and lignan. The motifs of LiP were predicted
by MEME tool. Statistical analysis and Multinomial Naive Bayes (MNB) algorithm
were used for the classification of two LiP protein groups. The results
demonstrated that molecular weight, isoelectric point, aliphatic, extinction
coefficient and random coil percentage of LiPs in fungi and bacteria were
significantly different between these two groups. The classification of these two
groups based on the concept of PseAAC showed over 80% accuracy. The binding free
energy between bacterial LiPs and lignan is significantly more than fungi LiP and
ligand. The aliphatic and instability of most important motifs of bacteria and
fungi were significantly different. In conclusion, the results indicated that
computational techniques could provide useful information for comparing fungal
and bacterial LiPs. These results can also explain that there is a relationship
between efficacy and physicochemical properties of LiPs.
PMID- 27615150
TI - The interplay between population stability and food-web topology predicts the
occurrence of motifs in complex food-webs.
AB - In this paper, we analyzed the occurrence of motifs (modules) in empirical food
webs from different ecosystem types. Differently from previous studies, our
analysis did not relied on randomized networks with specific a priori
assumptions, which has been demonstrated to produce inconsistent patterns. We
aimed to evaluate the interplay between population dynamics and food-web
topology, and its consequences to module occurrences in complex food-webs. We
evaluated 13 arrangements of three-species modules and 199 arrangements of four
species modules. For each module, we assembled, a corresponding Jacobian
predation matrix, and evaluated the arrangements expected to persist after a
disturbance in the equilibrium of the populations dynamics (local stability). Our
general results were that (1) a limited set of stable arrangements occurs most
frequently; (2) the omnivory module is the only three-species module expected to
occur both in the stable and unstable region; (3) connectance and omnivory
affects the proportion of stable modules; and (4) the type of ecosystem influence
the proportion of stable modules. Further, we demonstrated that food-web topology
and population dynamics influenced module occurrences in natural communities;
presented a function for the ways that local stability increases the probability
of module occurrence; and highlighted the use of omnivory degree to access the
effect of feeding at more than one trophic level on food-web stability.
PMID- 27615151
TI - Tailoring Spin Textures in Complex Oxide Micromagnets.
AB - Engineered topological spin textures with submicron dimensions in magnetic
materials have emerged in recent years as the building blocks for various spin
based memory devices. Examples of these magnetic configurations include magnetic
skyrmions, vortices, and domain walls. Here, we show the ability to control and
characterize the evolution of spin textures in complex oxide micromagnets as a
function of temperature through the delicate balance of fundamental materials
parameters, micromagnet geometries, and epitaxial strain. These results
demonstrate that in order to fully describe the observed spin textures, it is
necessary to account for the spatial variation of the magnetic parameters within
the micromagnet. This study provides the framework to accurately characterize
such structures, leading to efficient design of spin-based memory devices based
on complex oxide thin films.
PMID- 27615152
TI - Development of a lateralization index for intramedullary astrocytomas and
ependymomas.
AB - INTRODUCTION: Intramedullary ependymomas are classically described as tumors
developing in the center of the spinal cord, whereas intramedullary astrocytomas
are more dispersed. This description only remains approximate. The aim of this
study was to establish a lateralization index (LI), which is based on
radiological measurements and may help in differentiating the two tumors.
MATERIAL AND METHODS: Retrospective analysis based on the analysis of MRI of
patients operated on for intramedullary astrocytoma or ependymoma in the
Neurosurgical Department of Bicetre Hospital. We consider the distance between
the center of the spinal cord and the lateral edge of the tumor, this measurement
is called a. Measurement b is the maximal axial diameter of the tumor, measured
on the same axis of a. Measurements are made on T1-weighted axial MR images after
gadolinium administration. The LI is calculated by the ratio a/b. RESULTS: Twenty
one patients were included in the study, 11 astrocytomas and 10 ependymomas. The
average LI was 0.7425 (0.5611 to 1.1673) for astrocytomas and 0.5462 (0.5276 to
0.5995) for ependymomas. The difference of LI between the two types of tumors was
statistically significant (P<0.05). CONCLUSION: This study confirms that for
ependymomas the LI is close to 0.5, which is the value of a completely centered
tumor, unlike astrocytomas. The LI can be an additional tool in helping to
differentiate the two types of tumors on the preoperative imagery.
PMID- 27615153
TI - Minimally invasive approach for the treatment of lumbar epidural arteriovenous
fistulas with intradural venous reflux.
AB - BACKGROUND: Vascular lesions of the spinal cord are increasingly recognized. The
most common types of these lesions are dural arteriovenous fistulas (AVFs)
whereas, extradural AVFs are a very rare type of spinal AVF and can be associated
with either extradural or intradural venous reflux. This results in neurological
deficits through congestive or compressive myeloradiculopathy. These lesions must
be treated to allow stabilization or improvement of neurologic status, either by
endovascular therapy or microsurgical interruption. However, because some
patients are not amenable to endovascular treatment, surgery is often warranted,
which usually involves hemi- or bilateral laminectomy following a midline
approach with bilateral muscle stripping. The main drawback of this procedure is
directly related to the morbidity of the approach. Although, minimally invasive
approaches are likely to overcome this drawback, there is a lack of reported
experience supporting their use for treating spinal dural AVFs. CASE
PRESENTATION: Two patients, aged 62 and 79 years old, presented with rapidly
progressive myelopathy characterized by paraparesis and sphincter disturbance.
Spinal magnetic resonance imaging showed spinal cord oedema with perimedullary
flow voids in both cases. Digital subtraction angiography revealed extradural
AVFs associated with perimedullary venous reflux. Endovascular therapy was not
feasible. Both patients were treated with microsurgical interruption of the
intradural vein through a non-expendable retractor. Complete exclusion was
confirmed on postoperative angiography, resulting in resolution of spinal cord
edema and improved neurological functional status at 2-year follow-up.
CONCLUSION: The minimally invasive surgical treatment of spinal AVFs with
epidural venous reflux is safe and effective. This approach is a valuable
alternative to endovascular therapy and the standard open microsurgical approach.
PMID- 27615154
TI - Intramedullary cavernoma: A surgical resection technique.
AB - Intramedullary spinal cavernoma is a rare vascular disease constituting 5-12% of
all spinal vascular tumors. The clinical course is usually characterized either
by an acute neurological deterioration, recurrent episodes of neurological
deficits or by a slowly progressive neurological decline. Microsurgical removal
is recommended when the symptoms become clinically relevant and the lesion
appears accessible. In this article, we present a surgical technique to
completely resect an intramedullary cavernoma with the aid of intraoperative
electrophysiological monitoring and intraoperative real-time ultrasound guidance.
A brief description of current management of this pathology is also presented.
PMID- 27615155
TI - Clinical characteristics of pulmonary nocardiosis in immunocompetent patients.
AB - Pulmonary nocardiosis is a rare but potentially serious infection typically in
immunosuppressed patients (ISPs). It is also known to occur in immunocompetent
patients (ICPs). However, little is currently known regarding the clinical
characteristics and radiographic findings of pulmonary nocardiosis specifically
in ICPs. In this study, 30 patients with pulmonary nocardiosis were identified
and 10 were considered to be colonized. Of all patients with pulmonary
nocardiosis, 12 patients were ICPs and 18 were ISPs. Although half of ISPs were
infected by Nocardia nova, ICPs were affected by various Nocardia species.
Compared with ISPs, chest CT findings of ICPs showed a higher prevalence of
bronchiectasis (67% vs 6%, p < .01) and centrilobular nodular opacities (67% vs
11%, p < .01), both of which are often seen in pulmonary nontuberculous
mycobacterial disease. Additionally, nontuberculous mycobacterium was isolated
from 6 of 21 ICPs with positive Nocardia species culture. Therefore, we recommend
that physicians carefully differentiate pulmonary nocardiosis from pulmonary
nontuberculous mycobacterial disease in ICPs.
PMID- 27615156
TI - Trauma undertriage and overtriage rates: are we using the wrong formulas?
PMID- 27615157
TI - Patients' perspectives on the insufficiency of scales to rate their pain in the
ED.
PMID- 27615158
TI - Alleviating GAA Repeat Induced Transcriptional Silencing of the Friedreich's
Ataxia Gene During Somatic Cell Reprogramming.
AB - Friedreich's ataxia (FRDA) is the most common autosomal recessive ataxia. This
severe neurodegenerative disease is caused by an expansion of guanine-adenine
adenine (GAA) repeats located in the first intron of the frataxin (FXN) gene,
which represses its transcription. Although transcriptional silencing is
associated with heterochromatin-like changes in the vicinity of the expanded
GAAs, the exact mechanism and pathways involved in transcriptional inhibition are
largely unknown. As major remodeling of the epigenome is associated with somatic
cell reprogramming, modulating chromatin modification pathways during the
cellular transition from a somatic to a pluripotent state is likely to generate
permanent changes to the epigenetic landscape. We hypothesize that the epigenetic
modifications in the vicinity of the GAA repeats can be reversed by
pharmacological modulation during somatic cell reprogramming. We reprogrammed
FRDA fibroblasts into induced pluripotent stem cells (iPSCs) in the presence of
various small molecules that target DNA methylation and histone acetylation and
methylation. Treatment of FRDA iPSCs with two compounds, sodium butyrate (NaB)
and Parnate, led to an increase in FXN expression and correction of repressive
marks at the FXN locus, which persisted for several passages. However, prolonged
culture of the epigenetically modified FRDA iPSCs led to progressive expansions
of the GAA repeats and a corresponding decrease in FXN expression. Furthermore,
we uncovered that differentiation of these iPSCs into neurons also results in
resilencing of the FXN gene. Taken together, these results demonstrate that
transcriptional repression caused by long GAA repeat tracts can be partially or
transiently reversed by altering particular epigenetic modifications, thus
revealing possibilities for detailed analyses of silencing mechanism and
development of new therapeutic approaches for FRDA.
PMID- 27615159
TI - Regulation of cell-cell fusion by nanotopography.
AB - Cell-cell fusion is fundamental to a multitude of biological processes ranging
from cell differentiation and embryogenesis to cancer metastasis and biomaterial
tissue interactions. Fusogenic cells are exposed to biochemical and biophysical
factors, which could potentially alter cell behavior. While biochemical inducers
of fusion such as cytokines and kinases have been identified, little is known
about the biophysical regulation of cell-cell fusion. Here, we designed
experiments to examine cell-cell fusion using bulk metallic glass (BMG) nanorod
arrays with varying biophysical cues, i.e. nanotopography and stiffness. Through
independent variation of stiffness and topography, we found that nanotopography
constitutes the primary biophysical cue that can override biochemical signals to
attenuate fusion. Specifically, nanotopography restricts cytoskeletal remodeling
associated signaling, which leads to reduced fusion. This finding expands our
fundamental understanding of the nanoscale biophysical regulation of cell fusion
and can be exploited in biomaterials design to induce desirable biomaterial
tissue interactions.
PMID- 27615162
TI - [Research funding: a bottleneck for economic growth].
PMID- 27615161
TI - Adherence rates to ferric citrate as compared to active control in patients with
end stage kidney disease on dialysis.
AB - INTRODUCTION: Oral phosphate binders are the main stay of treatment of
hyperphosphatemia. Adherence rates to ferric citrate, a recently approved
phosphate binder, are unknown. METHODS: We conducted a post-hoc analysis to
evaluate whether adherence rates were different for ferric citrate vs. active
control in 412 subjects with end stage kidney disease (ESKD) who were randomized
to ferric citrate vs. active control (sevelamer carbonate and/or calcium
acetate). Adherence was defined as percent of actual number of pills taken to
total number of pills prescribed. FINDINGS: There were no significant differences
in baseline characteristics including gender, race/ethnicity, and age between the
ferric citrate and active control groups. Baseline phosphorus, calcium, and
parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and
81.7% (15.9) in the ferric citrate and active control groups, respectively (P =
0.88). Adherence remained similar between both groups after adjusting for gender,
race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean
[95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active
control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic
nephropathy did not influence adherence to the prescribed phosphate binder.
Subjects with CVD had lower adherence rates to phosphate binder; this was
significant only in the active control group. DISCUSSION: Adherence rates to the
phosphate binder, ferric citrate, were similar to adherence rates to active
control. Similar adherence rates to ferric citrate are notable since tolerance to
active control was an entry criteria and the study was open label. Gender,
race/ethnicity, nor age influenced adherence.
PMID- 27615160
TI - Endothelial dysfunction correlates with decompression bubbles in rats.
AB - Previous studies have documented that decompression led to endothelial
dysfunction with controversial results. This study aimed to clarify the
relationship between endothelial dysfunction, bubble formation and decompression
rate. Rats were subjected to simulated air dives with one of four decompression
rates: one slow and three rapid. Bubble formation was detected ultrasonically
following decompression for two hours, before measurement of endothelial related
indices. Bubbles were found in only rapid-decompressed rats and the amount
correlated with decompression rate with significant variability. Serum levels of
ET-1, 6-keto-PGF1alpha, ICAM-1, VCAM-1 and MDA, lung Wet/Dry weight ratio and
histological score increased, serum NO decreased following rapid decompression.
Endothelial-dependent vasodilatation to Ach was reduced in pulmonary artery rings
among rapid-decompressed rats. Near all the above changes correlated
significantly with bubble amounts. The results suggest that bubbles may be the
causative agent of decompression-induced endothelial damage and bubble amount is
of clinical significance in assessing decompression stress. Furthermore, serum
levels of ET-1 and MDA may serve as sensitive biomarkers with the capacity to
indicate endothelial dysfunction and decompression stress following dives.
PMID- 27615163
TI - [The ancestral gene repertoire of animal stem cells].
PMID- 27615164
TI - [Female-typical neural activation in women with complete androgen insensitivity
syndrome].
PMID- 27615165
TI - [Antibodies that kill HIV-1-infected cells].
PMID- 27615166
TI - [Beyond the brain: huntingtin in breast cancers].
PMID- 27615167
TI - [When immunoglobulin genes assemble with bricks from other chromosomes].
PMID- 27615168
TI - [Ancient Yersinia pestis genomes for tracing the origins and spreading of plague
past epidemics].
PMID- 27615169
TI - [Protein carbamylation: when protein and chronologic ageings meet].
PMID- 27615170
TI - [Astroglial modulation of deep brain stimulation in depression].
PMID- 27615171
TI - [Chemokine receptors expression on T cells: contribution to diagnosis of melanoma
metastasis dissemination status].
PMID- 27615172
TI - [Mesolimbic dopamine neuron stimulation is sufficient for the progression to
addiction].
PMID- 27615173
TI - [Human respiratory neurotropic coronaviruses: an ambiguous relationship between
neurovirulence and protein cleavage].
PMID- 27615175
TI - [Crosstalk between the tumor suppressor p53 and Fe-S cluster biogenesis].
PMID- 27615174
TI - [Parasitic wasps have hijacked viruses several times during their evolution].
PMID- 27615176
TI - [Perforin, granzyme and granulysin association to kill intracellular parasites].
PMID- 27615177
TI - [EGFR, liver regeneration and carcinogenesis: not the only culprit].
PMID- 27615178
TI - [Butterfly effect and cancer: how a mechanical pressure induced in vivo leads to
tumorigenesis in neighboring healthy cells].
PMID- 27615179
TI - [Sphingosine kinase-1: role in non alcoholic fatty liver disease].
PMID- 27615180
TI - [Cancer cell plasticity and metastatic dissemination].
AB - Metastatic dissemination consists of a sequence of events resulting in the
invasion by cancer cells of tissues located away from the primary tumour. This
process is highly inefficient, since each event represents an obstacle that only
a limited number of cells can overcome. However, two biological phenomena
intrinsically linked with tumour development facilitate the dissemination of
cancer cells throughout the body and promote the formation of metastases, namely
the genetic diversity of cancer cells within a given tumour, which arises from
their genetic instability and from successive clonal expansions, and cellular
plasticity conveyed to the cells by micro-environmental signals. Genetic
diversity increases the probability of selecting cells that are intrinsically
resistant to biological and physical constraints encountered during metastatic
dissemination, whereas cellular plasticity provides cells with the capacity to
adapt to stressful conditions and to changes in the microenvironment. The
epithelial-mesenchymal transition, an embryonic trans-differentiation process
frequently reactivated during tumour development, plays an important role in that
context by endowing tumor cells with a unique capacity of motility, survival and
adaptability to the novel environments and stresses encountered during the
invasion-metastasis cascade.
PMID- 27615181
TI - [Are the cobalt hip prosthesis dangerous?].
AB - The placement of a hip prosthesis is one of the most common orthopedic surgical
procedures. Some implants contain metal and are therefore capable of releasing
metal particles like cobalt in patients who wear metal prostheses. Cobalt can be
responsible of local toxicity (including metallosis, hypersensitivity reaction,
and benign tumor) or systemic toxicity (including cardiomyopathy, polycythemia,
hypothyroidism, and neurological disorders). To monitor potential toxicity of
metal hip prostheses, an annual monitoring of patients implanted is recommended
and includes clinical examination, radiological examination and blood cobalt
determination. The cobalt concentration in blood allows to estimate the risk of
toxicity and to evaluate the performance of the implant. The currently
recommended threshold value is equal to 7 ug of cobalt per liter of blood. Our
study, conducted on 251 patients over a period of 4 years, has shown that the
cobalt concentration average was 2.51 ug/l in blood, with 51 patients having a
cobaltemia higher than the threshold of 7 ug/l.
PMID- 27615182
TI - [Vaccination against hepatitis B: success and challenges].
AB - Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease
including cirrhosis and hepatocellular carcinoma. Effective vaccines have been
available since the early '80s. Vaccination against hepatitis B virus infection
has proved highly successful in reducing the disease burden, the development of
the carrier state and the hepatitis B-related morbidity and mortality in the
countries where vaccination has been implemented. Despite success and efficacy of
preventive vaccines, a huge number of chronically infected patients still remain.
Therapeutic vaccination may prove to be useful coupled with current antivirals
and other immunomodulatory approaches to treat these patients. This review
summarizes current unresolved issues and future perspectives on vaccination
required for global cure of hepatitis B virus infection.
PMID- 27615183
TI - [From the influence of genes to the influence of family and urban environment on
the nutritional status, activity, and physical condition of european urban
adolescents].
AB - HELENA was a cross-sectional study carried out from 2006 to 2007 in more than
3500 adolescents aged from 12.5 to 17.5 years old through 10 Europeans towns from
9 countries. Its objective was to assess adolescent nutritional status including:
body composition, biological markers, physical activity and fitness. This study
shown the high impact of socio-economic condition, life style and personal and
collective environment, dietary pattern (including breastfeeding), some genetic
mutations involved in adiposity and metabolism, physical activity level and
fitness on adolescent nutritional status.
PMID- 27615184
TI - [Transcranial direct current stimulation: new clinical roadmaps for psychiatric
research].
AB - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique
that has undergone intensive research over the past decade with promising
results. tDCS is based on the application of weak, direct current over the scalp,
leading to cortical hypo- or hyperpolarization according to the specified
parameters. Recent studies have shown that tDCS is able to induce potent changes
in cortical excitability as well as to elicit long-lasting modifications in brain
activity. Over the last decade, tDCS physiological mechanisms of action have been
intensively investigated. This research has given support for the investigation
of tDCS applications in a wide range of clinical populations, including patients
with post-stroke motor and language deficits, chronic pain, and tinnitus.
Recently, its efficacy to treat psychiatric conditions has been explored
increasingly. In this review, we will gather clinical studies involving tDCS to
ameliorate psychiatric symptoms and discuss reasonable next steps in this
direction.
PMID- 27615185
TI - [Cryo-microscopy, an alternative to the X-ray crystallography?].
AB - Recent technological advances have revolutionized the field of structural
biologists. Specifically, dramatic progress related to the development of new
electron microscopes and image capture (direct electron detection camera) and the
provision of new image analysis software has led to a breakthrough in terms of
resolution attained using cryo-electron transmission microscopy. It is thus
possible to calculate relatively quickly high-resolution structures of biological
molecules whom structural study still resists to more conventional methods such
as X-ray diffraction or nuclear magnetic resonance (NMR). These structures thus
obtained may also bring complementary structural information to those already
described by other methods. Some of these new structures resolved through cryo
electron microscopy revealed for the first time the precise operation of
essential mechanisms necessary for the good physiological process of a cell. The
ability to solve these structures at atomic resolution detail is essential for
the development of new drugs that target these proteins of therapeutic interest.
Thanks to these advanced techniques that we summarize in this revew, biological
and medical issues have now become accessible, whereas this approach was
inconceivable only five yeras ago. ?.
PMID- 27615186
TI - [Towards optical in vivo electrophysiology].
AB - Optical imaging of voltage indicators is a promising approach for detecting the
activity of neuronal circuits with high spatial and temporal resolution. In this
context, genetically encoded voltage indicators, combining genetic targeting and
optical readout of transmembrane voltage, represent a technological breaktrough
that will without doubt have a major impact in neuroscience. However, so far the
existing genetically encoded voltage indicators lacked the capabilities to detect
individual action potentials and fast spike trains in live animals. Here, we
present a novel indicator allowing high-fidelity imaging of individual spikes and
dentritic voltage dynamics in vivo. Used in combination with optogenetics, which
allows to manipulate neuronal activity, this opens the possibility of an all
optical electrophysiology.
PMID- 27615187
TI - [Shades of grays for implanting an enzymatic biofuel cell].
AB - An implanted biofuel cell (IBFC) is a novel device that provides the means to
create electricity from glucose and oxygen, using an original architecture for
the IBFC that provides efficient work inside a living organism. In the future
these IBFCs will be required to power implanted devices to assist failing
physiological functions in humans. The active ingredients of such IBFCs are
glucose oxidase at the anode and laccase at the cathode. These enzymes are
entrapped in a 3D network of conductive and insulated materials. This publication
solves the issue of the sterilization of such a complex device, using gamma
irradiation. A 12kGy dose was sufficient to show absence of implant infection in
all the implantations performed. We also prove in vitro functioning of both
bioelectrodes with a high dose of 42kGy.
PMID- 27615188
TI - [Symmetry is beauty - or is it? The rise and fall of fluctuating asymmetry].
AB - Fluctuating asymmetry is the stochastic, minor deviation from perfect symmetry in
bilaterally symmetrical organisms. It reflects the limit of developmental
precision. Such a precision can be influenced by various factors, both internal
(genetic mutations, stochastic variation at every levels of development) and
external (environmental influences). Fluctuating asymmetry has receive an extreme
attention for the past few decades, that culminated in the 90s: it has been used
as an estimator of heterozygosity, fitness, environmental stress, and widely
applied to human biology, sociobiology and psychology before being more or less
discredited in the early 2000s. The reasons for such an extreme popularity and
then disgrace are discussed here. Far from suggesting to abandon the study of
fluctuating asymmetry, we indicate some of the most promising research avenues.
?.
PMID- 27615189
TI - [Alzheimer, life, death, recognition].
PMID- 27615190
TI - [Does a cancer moonshot make sense?].
AB - The recently announced "Cancer moonshot" may be greeted with scepticism: the
previous "War on cancer" (1971) was not very successful. However the current plan
seems well targeted, with emphasis not only on research investment but also on a
strong effort to "break down silos" and ensure wide dissemination and use of
clinical and molecular data. One big uncertainty, however, is what will happen to
the programme after the 2016 presidential election... ?.
PMID- 27615191
TI - Phenomenological modelling and simulation of cell clusters in 3D cultures.
AB - Cell clustering and aggregation are fundamental processes in the development of
several tissues and the progression of many diseases. The formation of these
aggregates also has a direct impact on the oxygen concentration in their
surroundings due to cellular respiration and poor oxygen diffusion through
clusters. In this work, we propose a mathematical model that is capable of
simulating cell cluster formation in 3D cultures through combining a particle
based and a finite element approach to recreate complex experimental conditions.
Cells are modelled considering cell proliferation, cell death and cell-cell
mechanical interactions. Additionally, the oxygen concentration profile is
calculated through finite element analysis using a reaction-diffusion model that
considers cell oxygen consumption and diffusion through the extracellular matrix
and the cell clusters. In our model, the local oxygen concentration in the medium
determines both cell proliferation and cell death. Numerical predictions are also
compared with experimental data from the literature. The simulation results
indicate that our model can predict cell clustering, cluster growth and oxygen
distribution in 3D cultures. We conclude that the initial cell distribution, cell
death and cell proliferation dynamics determine the size and density of clusters.
Moreover, these phenomena are directly affected by the oxygen transport in the 3D
culture.
PMID- 27615192
TI - Ambulatory Blood Pressure Monitoring for the Effective Management of
Antihypertensive Drug Treatment.
AB - PURPOSE: This purpose of this article is to review the current recommendations
for ambulatory blood pressure measurement (ABPM) and the use of ABPM in assessing
treatment. METHODS: We review current international guidelines and undertake a
critical review of evidence supporting the clinical use of ABPM in effectively
managing antihypertensive drug treatment. FINDINGS: Current guidelines emphasize
the diagnostic superiority of ABPM, mainly from the ability of the technique to
identify sustained hypertension by allowing for the exclusion of white-coat
hypertension and by demonstrating the presence of masked hypertension. ABPM also
offers diagnostic insights into nocturnal patterns of blood pressure, such as
dipping and nondipping, reverse dipping, and excessive dipping, and the presence
of nocturnal hypertension; although less attention is given to the nocturnal
behavior of blood pressure in clinical practice, the nocturnal patterns of blood
pressure have particular relevance in assessing the response to blood pressure
lowering medication. Surprisingly, although the current guidelines give detailed
recommendations on the diagnostic potential and use of ABPM, there are scant
recommendations on the benefits and application of the technique for the
initiation of blood pressure-lowering therapy in clinical practice and virtually
no recommendations on how it might be used to assess the efficacy of drug
treatment. IMPLICATIONS: In view of a deficiency in the literature on the role of
ABPM in assess the efficacy of drug treatment, we put forward proposals to
correct this deficiency and guide the prescribing physician on the most
appropriate drug administration and dosage over time.
PMID- 27615193
TI - No childhood cancer survivor left behind.
PMID- 27615194
TI - Gene expression profiling of granule cells and Purkinje cells in the zebrafish
cerebellum.
AB - The structure of the neural circuitry of the cerebellum, which functions in some
types of motor learning and coordination, is generally conserved among
vertebrates. However, some cerebellar features are species specific. It is not
clear which genes are involved in forming these conserved and species-specific
structures and functions. This study uses zebrafish transgenic larvae expressing
fluorescent proteins in granule cells, Purkinje cells, or other cerebellar
neurons and glial cells to isolate each type of cerebellar cells by fluorescence
activated cell sorting and to profile their gene expressions by RNA sequencing
and in situ hybridization. We identify genes that are upregulated in granule
cells or Purkinje cells, including many genes that are also expressed in
mammalian cerebella. Comparison of the transcriptomes in granule cells and
Purkinje cells in zebrafish larvae reveals that more developmental genes are
expressed in granule cells, whereas more neuronal-function genes are expressed in
Purkinje cells. We show that some genes that are upregulated in granule cells or
Purkinje cells are also expressed in the cerebellum-like structures. Our data
provide a platform for understanding the development and function of the
cerebellar neural circuits in zebrafish and the evolution of cerebellar circuits
in vertebrates. J. Comp. Neurol. 525:1558-1585, 2017. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27615196
TI - [Chronic myelogenous leukemia: diagnosis and treatment].
AB - Chronic myelogenous leukemia is a clonal myeloproliferative neoplasm caused by
reciprocal translocation involving chromosomes 9 and 22 resulting in the
expression of a constitutively activated BCR-ABL1 tyrosine kinase that leads to
the malignant transformation of the hematopoietic stem cells. The condition was
previously known as a relentlessly progressive disease, but the treatment was
revolutionalized by the efficacy of tyrosine kinase inhibitors. Therapeutic
success is thus currently determined by the depth of molecular response achieved
on therapy. Multiple tyrosine kinase agents are available even for the first line
treatment. This guideline summarizes current focal points of the treatment of
chronic myelogenous leukemia specific to Hungary and provides definitions for
optimal molecular responses in this condition. Orv. Hetil., 2016, 157(37), 1459
1468.
PMID- 27615195
TI - Infiltrating cells from host brain restore the microglial population in grafted
cortical tissue.
AB - Transplantation of embryonic cortical tissue is considered as a promising therapy
for brain injury. Grafted neurons can reestablish neuronal network and improve
cortical function of the host brain. Microglia is a key player in regulating
neuronal survival and plasticity, but its activation and dynamics in grafted
cortical tissue remain unknown. Using two-photon intravital imaging and
parabiotic model, here we investigated the proliferation and source of microglia
in the donor region by transplanting embryonic cortical tissue into adult cortex.
Live imaging showed that the endogenous microglia of the grafted tissue were
rapidly lost after transplantation. Instead, host-derived microglia infiltrated
and colonized the graft. Parabiotic model suggested that the main source of
infiltrating cells is the parenchyma of the host brain. Colonized microglia
proliferated and experienced an extensive morphological transition and eventually
differentiated into resting ramified morphology. Collectively, these results
demonstrated that donor tissue has little contribution to the activated microglia
and host brain controls the microglial population in the graft.
PMID- 27615197
TI - [Multidisciplinary approach of hip fractures based on Hungarian data].
AB - Hip fractures are described by increased mortality, loss of quality of life,
functional decline and burden of diseases. They show a growing number worldwide.
The aim of the present study is to summarise the existing data on the incidence,
mortality, complications and rehabilitation of hip fractures, which relevance is
reported only by few studies. To reduce mortality and complications of hip
fractures the authors emphasize the importance of primary treatment within 12
hours, appropriate selection of surgical methods corresponding to the fracture
type after the assessment of femoral head viability, vitamin D supplementation,
same conditions for primary treatment during everyday of the week, and an
adequate acute treatment and rehabilitation for patient's general health status.
In the future integrated processing of multidisciplinary results of hip fractures
based on Hungarian data can support the development of efficient treatment and
prevention strategies, which can be advantageous for the patient, families,
health care system, and the society, too, by the reduction of costly
complications of hip fracture healing and mortality. Orv. Hetil., 2016, 157(37),
1469-1475.
PMID- 27615198
TI - [Adult advanced life support knowledge among ambulance officer/paramedic students
in Hungary].
AB - INTRODUCTION: Resuscitation knowledge is necessery for emergency care workers.
AIM: The aim of the authors was to investigate the advanced life support
knowledge of paramedic students in Hungary. METHOD: The research has been
executed at University of Pecs - Faculty of Health Sciences, Semmelweis
University - Faculty of Health Sciences, and University of Debrecen - Faculty of
Health Care. 97 students (n = 97) were involved in the study from third and
fourth grades. Data were recorded with a self-fill-in questionnaire. RESULTS:
Average scores were 67.79%. There was no significant difference between women and
men (p = 0.725). Younger age improved significantly scores (p = 0.003). Full-time
students completed the test significantly better than part-time students (p =
0.004). There was no significant difference between the students from different
locations (p = 0.254). CONCLUSIONS: It would be appropriate to increase the
number of resuscitation courses and to tighten the exams. The authors propose
that it would be reasonable to examine the students' practical skills. Orv.
Hetil., 2016, 157(37), 1476-1482.
PMID- 27615199
TI - [Complementary and alternative medicine use in surgical patients].
AB - INTRODUCTION: Due to the rise in use of non-conventional therapies, we may
consider the application of those in perioperative setting. AIM: The aims of the
authors were to measure the attitude of patients waiting for elective surgery
towards naturopathic methods, to determine their use and factors influencing
their usage. METHOD: A questionnaire was applied that patients filled in
individually and anonymously at the First Department of Surgery of Semmelweis
University, between July 1, 2014 and April 30, 2016. RESULTS: 63.6% of the 519
participants (response rate = 21%) were interested in non-conventional therapies,
and 26.8% of them applied naturopathy. In this group there were significantly
more females (p = 0.022; OR: 1.066-2.3635), patients with university degree (p =
0.000315; OR: 1.3915-3.1132), aged 40-49 (p = 0.012419; OR: 1.1451-3.2405), and
patients with hormonal disease (p = 0.039482; OR: 1.0186-5.7242). In terms of
lifetime prevalence the most popular methods were traditional Chinese medicine
(8.9%), alternative movement and massage therapy (7.5%) and homeopathy (7.3%).
Only 12.9% of the patients reported the application of these methods to the
physician. CONCLUSION: Surgical patients are interested in naturopathic methods,
and one-fourth of them actually use them even in the perioperative period. Orv.
Hetil., 2016, 157(37), 1483-1488.
PMID- 27615200
TI - [Comparison of the effect of multidrug resistance modifiers on prostate cancer,
mouse lymphoma and colon cancer cells].
AB - INTRODUCTION: The reason for unsuccessful tumor chemotherapy is related to
multidrug resistance. An important factor is the overexpression of efflux pumps,
such as P-glycoprotein. AIM: Amino- and amide-substituted steroid compounds and
phenothiazine derivatives were investigated in tumor models in vitro. METHOD: The
inhibition of P-glycoprotein was evaluated by flow cytometry and the interaction
of these compounds with doxorubicin was investigated as well. Molecular docking
was used to estimate the binding energies of the compounds to P-glycoprotein.
RESULTS: The aminosteroids showed anticancer activity on multidrug resistant
mouse T-lymphoma and prostate cancer cell lines. The combination of steroids and
doxorubicin potentiated its effect in hormone resistant prostate cancer cells.
Among the N-hydroxyalkyl-2-aminophenothiazines, secondary amines exhibited
anticancer effects on multidrug resistant colon adenocarcinoma cells.
CONCLUSIONS: The tested phenothiazine and steroid derivatives showed potent
anticancer activity, furthermore, the stereoisomerism of thioridazine did not
play a role in the antitumor properties. Neither steroids nor thioridazine
influenced apoptosis in hormone resistant cells. Orv. Hetil., 2016, 157(37), 1489
1495.
PMID- 27615202
TI - Barium sulfate micro- and nanoparticles as bioinert reference material in
particle toxicology.
AB - The inhalation of particles and their exposure to the bronchi and alveoli
constitute a major public health risk. Chemical as well as particle-related
properties are important factors for the biological response but are difficult to
separate from each other. Barium sulfate is a completely inert chemical compound,
therefore it is ideally suited to separate these two factors. The biological
response of rat alveolar macrophages (NR8383) was analyzed after exposure to
barium sulfate particles with three different diameters (40 nm, 270 nm, and 1.3
MUm, respectively) for 24 h in vitro (particle concentrations from 12.5 to 200
MUg mL-1). The particles were colloidally stabilized as well as fluorescently
labeled by carboxymethylcellulose, conjugated with 6-aminofluorescein. All kinds
of barium sulfate particles were efficiently taken up by NR8383 cells and found
inside endo-lysosomes, but never in the cell nucleus. Neither an inflammatory nor
a cytotoxic response was detected by the ability of dHL-60 and NR8383 cells to
migrate towards a chemotactic gradient (conditioned media of NR8383 cells) and by
the release of inflammatory mediators (CCL2, TNF-alpha, IL-6). The particles
neither caused apoptosis (up to 200 MUg mL-1) nor necrosis (up to 100 MUg mL-1).
As only adverse reaction, necrosis was found at a concentration of 200 MUg mL-1
of the largest barium sulfate particles (1.3 MUm). Barium sulfate particles are
ideally suited as bioinert control to study size-dependent effects such as uptake
mechanisms of intracellular distributions of pure particles, especially in
nanotoxicology.
PMID- 27615203
TI - A meta-synthesis of team members' voices: what we need and what we do to support
students who use AAC.
AB - The ultimate goal of AAC provision is to promote students' active participation
across settings through interactions involving a variety of partners and
functions. To achieve such outcomes, educational teams must collaborate and
consider the characteristics of students, their families, and relevant
environments during AAC assessment and intervention. To date, AAC team
collaboration has rarely been evaluated collectively outside intervention or case
study research. In this investigation, a meta-synthesis was conducted to review
qualitative studies of perspectives of team members on supporting students who
used AAC, ranging in age from kindergarten to post-secondary, in public schools
in the United States. Analyses yielded three primary themes necessary for
effective AAC services; inputs, activities, and outcomes. Implications and
recommendations for service providers and future researchers are described.
PMID- 27615204
TI - Risk of Small Bowel Obstruction After Robot-Assisted vs Open Radical
Prostatectomy.
AB - BACKGROUND AND PURPOSE: Whereas open radical prostatectomy is performed
extraperitoneally, minimally invasive radical prostatectomy is typically
performed within the peritoneal cavity. Our objective was to determine whether
minimally invasive radical prostatectomy is associated with an increased risk of
small bowel obstruction compared with open radical prostatectomy. PATIENTS AND
METHODS: In the U.S. Surveillance, Epidemiology and End Results (SEER)-Medicare
database, we identified 14,147 men found to have prostate cancer from 2000 to
2008 treated by open (n = 10,954) or minimally invasive (n = 3193) radical
prostatectomy. Multivariable Cox proportional hazard models were used to examine
the impact of surgical approach on the diagnosis of small bowel obstruction, as
well as the need for lysis of adhesions and exploratory laparotomy. RESULTS:
During a median follow-up of 45 and 76 months, respectively, the cumulative
incidence of small bowel obstruction was 3.7% for minimally invasive and 5.3% for
open radical prostatectomy (p = 0.0005). Lysis of adhesions occurred in 1.1% of
minimally invasive and 2.0% of open prostatectomy patients (p = 0.0003). On
multivariable analysis, there was no significant difference between minimally
invasive and open prostatectomy with respect to small bowel obstruction (HR 1.17,
95% CI 0.90, 1.52, p = 0.25) or lysis of adhesions (HR 0.87, 95% CI 0.50, 1.40, p
= 0.57). Limitations of the study include the retrospective design and use of
administrative claims data. CONCLUSIONS: Relative to open radical prostatectomy,
minimally invasive radical prostatectomy is not associated with an increased risk
of postoperative small bowel obstruction and lysis of adhesions.
PMID- 27615262
TI - Elevated HbA1c Levels Are Associated with the Blunted Autonomic Response Assessed
by Heart Rate Variability during Blood Volume Reduction.
AB - A high glycemic status increases the risk for autonomic dysfunction and
cardiovascular failure. The aim of this study was to investigate time-dependent
changes in the autonomic response and cardiovascular dynamics and the association
between the level of hemoglobin A1c (HbA1c) and autonomic response during blood
volume reduction. The study population consisted of 26 preoperative participants
who were scheduled for autologous blood donation (200-400 mL of whole blood) for
intraoperative or postoperative use. These participants without circulatory,
respiratory, or brain disease and diabetes mellitus were grouped according to
their HbA1c levels: < 6.5% (n = 18) and >= 6.5% (n = 8). We measured blood
pressure (BP) and analyzed heart rate variability (HRV) to quantify cardiac
autonomic regulation throughout blood donation. During blood volume reduction,
which was about 10% of the circulating blood volume, the BP and heart rate varied
within normal ranges in both groups. The high-frequency (HF) component, an index
of parasympathetic nerve activity, and the ratio of low-frequency (LF) to HF
components (LF/HF), an index of sympathetic nerve activity, significantly
decreased and increased with the progression of blood volume reduction,
respectively, in the HbA1c < 6.5% group. In contrast, in the HbA1c >= 6.5% group,
the HF component did not significantly change, and the increase in the LF/HF
ratio was delayed. Time-dependent changes in HRV were related to blood volume
reduction only in the HbA1c < 6.5% group. Thus, elevated HbA1c levels are
associated with the decrease in the autonomic response induced by blood volume
reduction.
PMID- 27615261
TI - Systematic review for orthodontic and orthopedic treatments for anterior open
bite in the mixed dentition.
AB - BACKGROUND: The treatment options for the early treatment of anterior open bite
are still controversial. The aim of this study was to evaluate the actual
available evidence on treatments of anterior open bite in the mixed dentition in
order to assess the effectiveness of the early treatment in reducing open bite,
the most efficacious treatment strategy and the stability of the results.
MATERIALS AND METHODS: A literature survey was done on November 15, 2015, by
means of appropriate Medical Subject Headings (MeSH) using the following
databases: PubMed, EMBASE, Cochrane Library, LILACS, VHL, and WEB OF SCIENCE.
Randomized clinical trials and studies with a control group (treated or
untreated) were then selected by two authors. Trials including patients with
syndromes or in the permanent dentition and studies concerning treatment with
extractions, full-fixed appliances, or surgery were not considered. Full articles
were retrieved for abstracts or titles that met the initial inclusion criteria or
lacked sufficient detail for immediate exclusion. RESULTS: Two thousand five
hundred sixty-nine studies about open bite were available; the search strategy
selected 240 of them. Twenty-four articles have been judged suitably for the
final review, and their relevant data were analyzed. DISCUSSION: Although this
review confirms the effectiveness of early treatment of open bite, particularly
when no-compliance strategies are employed, meta-analysis was unfeasible due to
lack of standardization, important methodological limitations, and shortcomings
of the studies. CONCLUSIONS: A more robust approach to trial design in terms of
methodology and error analysis is needed. Besides, more studies with longer
periods of follow-up are required.
PMID- 27615265
TI - Cloning, expression and purification of the complete domain of the eta-carbonic
anhydrase from Plasmodium falciparum.
AB - The antimalarial drugs are of fundamental importance in the control of malaria,
especially for the lack of efficient treatments and acquired resistance to the
existing drugs. For this reason, there is a continuous work in identifying novel,
less toxic and effective chemotherapies as well as new therapeutic targets
against the causative agents of malaria. In this context, a superfamily of
metalloenzymes named carbonic anhydrases (CAs, EC 4.2.1.1) has aroused a great
interest as druggable enzymes to limit the development of Plasmodium falciparum
gametocytes. CAs catalyze a common reaction in all life domains, the carbon
dioxide hydration to bicarbonate and protons (CO2 + H2O <=> HCO3- + H+). P.
falciparum synthesizes pyrimidines de novo starting from HCO3-, which is
generated from CO2 through the action of the eta-CA identified in the genome of
the protozoan. Here, we propose a procedure for the preparation of a wider
portion of the protozoan eta-CA, named PfCAdom (358 amino acid residues), with
respect to the truncated form prepared by Krungkrai et al. (PfCA1, 235 amino acid
residues). The results evidenced that the recombinant PfCAdom, produced as a His
tag fusion protein, was 2.7 times more active with respect the truncated form
PfCA1.
PMID- 27615264
TI - The Effect of Steroid Hormones on the Physical Performance of Boys and Girls
During an Olympic Weightlifting Competition.
AB - PURPOSE: To examine the steroid hormone effect on the physical performance of
young athletes during an Olympic weightlifting competition. METHODS: 26 boys and
26 girls were monitored across 2 weightlifting competitions. Pre- and post
competition testosterone (T), cortisol (C) and dehydroepiandrosterone-sulfate
(DHEA-s) were measured in blood, with pre-event free T (FT) and the free androgen
index (FAI) calculated. Body mass (BM) and weightlifting performance were
recorded. RESULTS: The boys had a larger BM, superior performance with more T, FT
and a higher FAI than girls (p < .01). Although C (32%) and DHEA-s (8%) levels
were elevated across competition, no sex differences in hormone reactivity were
seen. In boys, DHEA-s correlated with performance (r = .46), but not after
controlling for BM (r = .14). For girls, T correlated with performance (r =
0.51) after BM was controlled. CONCLUSION: The sex differences that emerge during
puberty were observable, whereby the boys were larger and stronger with a more
anabolic profile than girls. Individual DHEA-s (boys) and T (girls) levels were
related to performance, but BM appeared to be acting as a mediating (boys) or
suppressing (girls) variable. This adds new insight regarding the hormonal
contribution to competitive performance in young athletes.
PMID- 27615263
TI - Physiological Response of Escherichia coli O157:H7 Sakai to Dynamic Changes in
Temperature and Water Activity as Experienced during Carcass Chilling.
AB - Enterohemeorrhagic Escherichia coli is a leading cause of foodborne illness, with
the majority of cases linked to foods of bovine origin. Currently, no completely
effective method for controlling this pathogen during carcass processing exists.
Understanding how this pathogen behaves under those stress conditions experienced
on the carcass during chilling in cold air could offer opportunities for
development or improvement of effective decontamination processes. Therefore, we
studied the growth kinetics and physiological response of exponential phase E.
coli O157:H7 Sakai cultures upon an abrupt downshift in temperature and water
activity (from 35 degrees C aw 0.993 to 14 degrees C aw 0.967). A parallel
Biolog study was conducted to follow the phenotypic responses to 190 carbon
sources. Exposure of E. coli to combined cold and water activity stresses
resulted in a complex pattern of population changes. This pattern could be
divided into two main phases, including adaptation and regrowth phases, based on
growth kinetics and clustering analyses. The transcriptomic and proteomic studies
revealed that E. coli exhibited a "window" of cell susceptibility (i.e.
weaknesses) during adaptation phase. This included apparent DNA damage, the
downregulation of molecular chaperones and proteins associated with responses to
oxidative damage. However, E. coli also displayed a transient induction in the
RpoE-controlled envelope stress response and activation of the master stress
regulator RpoS and the Rcs phosphorelay system involved in colanic acid
biosynthesis. Increased expression was observed for several genes and/or proteins
involved in DNA repair, protein and peptide degradation, amino acid biosynthesis,
and carbohydrate catabolism and energy generation. Furthermore, the Biolog study
revealed reduced carbon source utilization during adaptation phase, indicating
the disruption of energy-generating processes. This study provides insight into
the physiological response of E. coli during exposure to combined cold and water
activity stress, which could be exploited to enhance the microbiological safety
of carcasses and related foods.
PMID- 27615266
TI - Extending minimally invasive approaches to concomitant aortic and mitral valve
surgery: are we ready?
PMID- 27615267
TI - Reoperations and catheter interventions in patients with transposition of the
great arteries after the arterial switch operation.
AB - OBJECTIVES: Reoperations and catheter interventions after the arterial switch
operation (ASO) are relatively rare, but their frequency varies among different
centres. They significantly impact the postoperative course of children with
transposition of the great arteries (TGA). The aim of this study was to assess
the frequency of reoperations and catheter interventions in patients with TGA
after the ASO and to identify the potential risk factors. METHODS: For this
retrospective case review study we included all consecutive 715 patients with TGA
who underwent the ASO in the Department of Cardiac Surgery between the years 1991
and 2015. All of the surgical procedures were performed by one cardiac surgery
team led by J.J.M., using the same surgical technique with his own specific
modifications. RESULTS: The overall early mortality after the ASO was 7.4%; late
mortality occurred in 15 cases (2.3%) and the mean clinical follow-up of our
cohort was 10.5 years. Early reoperations (<30 days after surgery) were performed
in 37 patients (5.1%). Reoperations were performed in 31 patients (4.7% of
survivors), and their risk factors were previous early reoperation and left
ventricle outflow tract obstruction, while isolated TGA reduced the risk of
reoperations. Catheter interventions were performed in 25 patients (3.8% of
survivors). In the majority of the cases, the indications for percutaneous
procedures were pulmonary stenosis and recoarctation of the aorta. The
statistically significant risk factors were aortic arch anomalies associated with
TGA and neopulmonary artery anastomosis with a patch, while isolated TGA
decreased the risk of reintervention. Freedom from cumulative reinterventions
after the ASO was 90.4% at 5 years; 88.0% at 10 years; 86.5% at 15 years and
86.5% from 20 to 25 years. CONCLUSION: The frequency of reoperations and
percutaneous interventions in patients with TGA after the ASO remains low. The
majority of the procedures are performed because of pulmonary stenosis and
recoarctation of aorta. Cardiac anomalies associated with TGA have a significant
impact on the incidence of reoperation and reintervention.
PMID- 27615269
TI - Lisinopril has a cardio-protective effect on experimental acute autoimmune
myocarditis in rats.
AB - PURPOSE: The present study investigated the effect of lisinopril on experimental
autoimmune myocarditis (EAM) in rats, a histologically similar model to human
acute myocarditis. ANIMALS AND METHODS: Twenty four, six week-old male Wistar
rats were randomly allocated into 4 groups of 6 rats each. Group I received no
treatment. Group II received lisinopril at a dose of 15 mg/kg/day suspended in 1
ml of 2% gum acacia daily, from day 1 to day 21. To induce myocarditis, animals
of groups III and IV were injected by 1 mg of porcine cardiac myosin on days 1
and 8. In addition, animals of group IV received lisinopril in gum acacia daily,
from day 1 to day 21. All rats were sacrificed on day 21. Serum levels of
creatine phosphokinase, troponin-T, tumor necrosis factor-alpha and interleukin-6
were estimated. Hearts were processed for histopathological, as well as
immunohistochemical study for thioredoxin (TRX) immunoreactivity. RESULTS: The
wall of hearts from rats of myocarditis-lisinopril group showed mild focal
myocarditis and a significant decrease of the mean percentage of pyknotic nuclei
in cardiomyocytes, coincident with a significant decrease in serum biomarkers
levels and TRX immunoreactivity, compared to myocarditis group. CONCLUSION: The
present study suggested a cardio-protective effect of lisinopril on acute EAM in
rats, probably through a mechanism related to its suppressive effect on
angiotensin II formation.
PMID- 27615268
TI - Pharyngo-oesophageal perforation following anterior cervical discectomy and
fusion: management and results.
AB - OBJECTIVES: Pharyngo-oesophageal perforation is a rare, life-threatening
complication of anterior cervical discectomy and fusion surgery; its management
remains poorly defined. We reviewed our experience to understand the treatment of
this dreadful complication. METHODS: Data regarding the demographics, clinical
course, diagnosis, management and outcomes of 15 cases of pharyngo-oesophageal
perforations in 14 patients were collected during the period from 2003 to 2016.
RESULTS: Pharyngo-oesophageal perforation occurred at a median of 32 days (range
1 day-102 months) after anterior cervical discectomy and fusion surgery. Clinical
manifestations included neck abscesses and cutaneous fistulas (10 cases),
cervical swelling (two cases), salivary leakage from cervicotomy (two cases),
dysphagia, halitosis and regurgitation (one case). In all cases, conservative
management was utilized. Two patients affected by minor external fistulas were
successfully managed conservatively. In 13 cases, the following surgery was
performed: (i) radical bone debridement, total or partial removal of spine
fixation devices, autologous bone graft insertion or plate/cage replacement in
one case each; (ii) anatomical suture of the fistula; or (iii) suture line
reinforcement with myoplasty (in 11/13 cases). Perforation recurred in three
cases. One patient underwent reoperation. The other two patients were treated
conservatively At a median follow-up of 82 months (range 1-157 months), all
patients exhibited permanent resolution of the perforation. CONCLUSIONS: Patients
with minimal leaks in the absence of systemic infection can be managed
conservatively. For cases of large fistulas with systemic infection, we recommend
partial or total removal of the fixation devices, direct suture of the
oesophageal defect and coverage with tissue flaps.
PMID- 27615270
TI - Investigating the Effects of Systemically Administered Strontium Ranelate on
Alveolar Bone Loss Histomorphometrically and Histopathologically on Experimental
Periodontitis in Rats.
AB - BACKGROUND: The aim of this study is to investigate effects of strontium ranelate
(SR) on alveolar bone loss (ABL) in rats with experimental periodontitis.
METHODS: Forty Wistar rats were randomly divided into five groups: 1) control (n
= 8); 2) ligated (n = 8); 3) 300 mg/kg SR (SR300, n = 8); 4) 625 mg/kg SR (SR625,
n = 8); and 5) 900 mg/kg SR (SR900, n = 8). To create experimental periodontitis,
4/0 silk ligatures were inserted submarginally around first molars at the right
mandible. After 11 days, rats were sacrificed. ABL was calculated by measuring
cemento-enamel junction and alveolar crest distance. Interleukin (IL)-1beta,
osteoprotegerin (OPG), and bone-specific alkaline phosphatase (BALP) serum levels
were determined by enzyme-linked immunosorbent assay. Histopathologic analysis
was used to evaluate inflammatory cell infiltration, numbers of osteoblasts and
osteoclasts, and receptor activator of nuclear factor-kappa B ligand (RANKL)
activity. RESULTS: ABL was significantly lower in SR900 group than in the ligated
group (P <0.05). Osteoclast numbers in ligated group were significantly higher
than in the control, SR300, and SR900 groups (P <0.05). In ligated, SR625, and
SR900 groups, significantly higher osteoblast numbers were detected than in
control group (P <0.05). Osteoblast numbers in SR625 group were significantly
higher than in the SR300 group (P <0.05). RANKL activities in SR900 and control
groups were close to each other (P >0.05). Serum IL-1beta, OPG, and BALP levels
revealed no significant difference (P >0.05). CONCLUSION: It can be concluded
that SR can reduce RANKL activity and osteoclast numbers, as well as ABL.
PMID- 27615271
TI - Cytokines, Hepatic Fibrosis, and Antiretroviral Therapy Role in Neurocognitive
Disorders HIV Related.
AB - The HIV may trigger a process of neuronal loss and axonal degeneration throughout
the brain, which is carried on by the immune system releasing of proinflammatory
cytokines, so that chronic inflammation associated with dysregulated innate
immune response, glial cell dysfunction, and adverse antiretroviral therapy (ART)
effect play an important role causing milder HIV-associated neurocognitive
disorders or asymptomatic neurocognitive impairment. All patients have been
tested for neurocognitive functioning through a comprehensive, five-domain
neuropsychological battery performed in the study. Human cytokine (interleukin
[IL]-6, IL-8, IL-18, and tumor necrosis factor [TNF]-alpha) and brain-derived
neurotrophic factor serum levels were quantified using ELISAs, and the hepatic
fibrosis was estimated using the noninvasive Fibrosis 4 (FIB-4) score. The study
showed a group of 40 HIV-infected individuals and it was observed that almost 40%
of HIV+ individuals, even if clinically asymptomatic, displayed some degree of
neurocognitive dysfunction, compared to normative performance standards, at least
in two cognitive areas. The functions affected the most were memory, attention,
executive function, and psychomotor processing speed. Three cytokines (IL-6, IL
8, and IL-18) to be significantly linked to test results in specific
neurocognitive domain were found. Treatments with nucleoside reverse
transcriptase inhibitor plus non-nucleoside reverse transcriptase inhibitor alone
were instead associated with poor neurocognitive outcome, especially in verbal
fluency, fine motility, and Zung Depression Scale. Elevated value of FIB-4 score
showed an opposite connection with cognitive performance as well, underlining the
direct association between hepatic steatosis and neurocognitive deficit. The
cytokine panel and the FIB-4 score can predict presence or worsening of
neurocognitive functions in HIV-infected individuals. An ART switch can be
suggested according to the neurocognitive domain involved the most, advising a
therapy with protease inhibitors or/and integrase inhibitors to improve fluency,
executive functions, and to prevent depression.
PMID- 27615272
TI - Role of respiratory changes in the modulation of arterial pressure in rats
submitted to sino-aortic denervation.
AB - NEW FINDINGS: What is the central question of this study? The arterial baroreflex
regulates arterial pressure within a narrow range of variation. After sino-aortic
denervation (SAD), rats show a large increase in arterial pressure variability,
but mean arterial pressure levels remain similar to those of control rats.
Considering that breathing influences the control of arterial pressure, the
question is: to what extent does SAD cause changes in breathing? What is the main
finding and its importance? Removal of arterial baroreceptors produced changes in
breathing in rats, marked by a reduction in respiratory frequency, but not
hypertension. These findings are indicative of a possible interaction of
respiratory and autonomic neural mechanisms in the regulation of arterial
pressure after SAD. Sino-aortic denervated (SAD) rats exhibit a mean arterial
pressure (MAP) similar to that of control rats. Given that respiration modulates
MAP, we hypothesized that conscious SAD rats show respiratory changes associated
with the normal MAP. In this study, we evaluated the cardiovascular and
respiratory activities and arterial blood gases in control and SAD rats. Male
juvenile Wistar rats (postnatal day 19-21) were submitted to SAD, sham surgery or
selective removal of the carotid bodies (CBX), and the three groups were
evaluated 10 days after the surgery (SAD, n = 21; Sham, n = 18; and CBX, n = 13).
The MAP in Sham, SAD and CBX groups was similar (P > 0.05), but the variability
of MAP was significantly higher in SAD than in Sham and CBX rats (P < 0.0001).
The duration of expiration and inspiration increased in SAD rats compared with
Sham and CBX rats, which resulted in a reduced respiratory frequency and minute
ventilation (P < 0.05). The arterial partial pressure of O2 and the haemoglobin
saturation were reduced in SAD and CBX compared with Sham rats, whereas the
arterial partial pressure of CO2 was increased in SAD compared with Sham rats.
The short- and long-term respiratory variability were significantly higher in SAD
than in Sham and CBX rats (P < 0.05). In addition, the reductions in MAP during
deep breaths were greater in SAD than in Sham and CBX rats (P < 0.0001). The data
show that SAD rats exhibit respiratory changes, which may be one of the
compensatory mechanisms associated with the maintenance of normal levels of MAP
in the absence of arterial baroreceptors.
PMID- 27615274
TI - A Review of Childhood Physical Activity, Brain, and Cognition: Perspectives on
the Future.
AB - This manuscript, which arose from the inaugural Tom Rowland Lecture Series at the
2016 North American Society for Pediatric Exercise Medicine conference, provides
a brief descriptive review of what is known (i.e., the state of the science)
regarding the relation of childhood physical activity (PA) and cardiorespiratory
fitness (CRF) to brain health, cognition, and academic outcomes. Gaps in the
knowledgebase are identified, including characteristics of the PA stimulus that
promotes changes in brain and cognition, whether critical periods in development
exist in which PA/CRF may have a disproportionately large influence, the
understanding of individual difference factors, and the influence upon learning.
Lastly, several possible directions for future research are proposed. Although
the field of childhood PA, CRF, brain, and cognition is rapidly expanding, there
is considerable room for future growth. This manuscript may be helpful in shaping
that future growth, with the goal of improving lifelong health and effective
functioning.
PMID- 27615273
TI - Feasibility and applicability of diffusion-weighted and dynamic contrast-enhanced
magnetic resonance imaging in routine assessments of children with high-grade
gliomas.
AB - Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance
imaging (MRI) have been used as imaging biomarkers in adults with high-grade
gliomas (HGGs). We incorporated free-breathing DW-MRI and DCE-MRI, at a single
time point, in the routine follow-up of five children (median age 9 years, range
8-15) with histologically confirmed HGG within a prospective imaging study. It
was feasible to incorporate DW-MRI and DCE-MRI in routine assessments of children
with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median
ADC100-1000 significantly correlated with longer survival in our sample.
PMID- 27615275
TI - Free-Carrier-Compensated Charged Domain Walls Produced with Super-Bandgap
Illumination in Insulating Ferroelectrics.
AB - Charged domain walls in ferroelectrics are movable and electronically conducting
interfaces inside insulating materials. A simple and reliable method for their
artificial production with ultraviolet (UV) light is described. The UV
illumination produces free carriers in ferroelectric bulk, which simultaneously
promotes the formation of charged domain walls and provides charge for their
compensation.
PMID- 27615277
TI - What is known about pediatric antiphospholipid syndrome?
AB - INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease
characterized by vascular thrombosis and/or pregnancy morbidity associated with
the persistent presence of antiphospholipid antibodies (aPL) including lupus
anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein
I antibodies (abeta2GPI). AREAS COVERED: APS is considered as the most common
acquired hypercoagulation state of autoimmune origin in children. Unfortunately,
data about incidence, prevalence, thrombosis risk and effective treatment in
paediatric APS are limited and unmethodical. Expert commentary: This review
summarizes recent clinical, laboratory and therapy characterization of paediatric
APS and emphasizes the differences between paediatric and adult populations.
PMID- 27615276
TI - Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis.
AB - Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs)
derived from the bone marrow have shown promise as a cell type for cartilage
regeneration strategies. In this study, sodium tungstate (Na2WO4), which is an
insulin mimetic, was evaluated for the first time as an inductive factor to
enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional
electrospun scaffolds in growth medium (GM), complete chondrogenic induction
medium (CCM) containing insulin, and CCM without insulin. Na2WO4 was added to the
media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic
differentiation was assessed by biochemical analyses, immunostaining, and gene
expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS)
was also investigated. The chondrogenic differentiation of MSCs was enhanced in
the presence of low concentrations of Na2WO4 compared to control, without Na2WO4.
In the induction medium containing insulin, cells in 0.01 mM Na2WO4 produced
significantly higher sulfated glycosaminoglycans, collagen type II, and
chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM
Na2WO4 had significantly higher collagen II production and significantly higher
sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and
induction medium without insulin containing low concentrations of Na2WO4 also
expressed chondrogenic markers. Na2WO4 did not stimulate PBMC proliferation or
apoptosis. The results demonstrate that Na2WO4 enhances chondrogenic
differentiation of MSCs, does not have a toxic effect, and may be useful for MSC
based approaches for cartilage repair.
PMID- 27615278
TI - A meta-analysis of sodium profiling techniques and the impact on intradialytic
hypotension.
AB - Introduction Hemodialysis has improved in recent years, however, despite such
improvements, intra-dialytic hypotensive episodes still persist which can lead to
a reduction in the overall effectiveness of the treatment. Profiling sodium
levels during dialysis can improve vascular refilling and therefore may prevent
hypotensive events. A number of profiling methods exist and this meta-analysis
set out to examine the effectiveness of these methods. Methods To assess the
effectiveness of hemodialysis sodium profiling techniques. A review and meta
analysis analytical framework was used. A search was conducted using Medline,
Embase and CINAHL, Scopus and Web of Knowledge between 1946 and 2014 of published
English-language peer reviewed randomized control studies. In total 10 articles
were retrieved and included in the review. All data was abstracted with a
standardized data collection form. Stata 11.2 (Stata Corp) was used to analyse
the data. Actual numbers of hypotensive events were pooled between studies.
Analysis of subgroups was performed on sodium profile type. The data were further
investigated using meta-regression. Publication bias was also tested. Findings
Stepwise profiling was shown to be statistically significantly effective in
reducing intradialytic episodes. Results demonstrated that linear sodium
profiling was not effective in reducing hypotensive events during dialysis.
Discussion This review has shown that using stepwise profiling is more effective
at reducing intra-dialytic symptoms than other profiling methods. There was no
evidence that linear profiling method was any more effective than conventional
dialysis and in fact the results showed the reverse.
PMID- 27615279
TI - Mining long noncoding RNA in livestock.
AB - Genome-wide association studies in livestock based on high-resolution genotyping
and sequencing have revealed that the majority of signals associated with complex
phenotypic traits are located outside of annotated protein-coding regions in the
genome. The approaches of next-generation sequencing applied to whole
transcriptome and chromatin profiles have provided information about existing
genome-wide transcriptional activity and have revealed that the genomes are
templates for thousands of long noncoding transcripts (lncRNAs). Despite their
lack of coding capacity, many lncRNAs have been found to play functional roles in
a variety of biological processes, which is adding a novel regulatory network to
the complex structural organization and function of the genome. Here, we
summarize main features of lncRNAs, provide an overview about computational tools
and pipelines used for identification of lncRNAs from whole transcriptome
datasets and review the current state of knowledge about lncRNAs in livestock
species. Although lncRNAs are increasingly emerging as an integral component of
the regulatory information encoded in the genome, the complexity of the
transcriptomes in domesticated animals is inadequately characterized in
comparison to human and mouse. Progress in elucidating whole transcriptomes of
livestock species, including identification, functional annotation and
characterization of lncRNAs, will be essential for a better understanding of
basic biological processes associated with developmental, metabolic and
immunological regulation and adaptation and phenotypic variation of complex
traits in domesticated animals.
PMID- 27615280
TI - Oxygen and differentiation status modulate the effect of X-ray irradiation on
physiology and mitochondrial proteome of human neuroblastoma cells.
AB - Cytotoxic effects, including oxidative stress, of low linear energy transfer
(LET)-ionizing radiation are often underestimated and studies of their mechanisms
using cell culture models are widely conducted with cells cultivated at
atmospheric oxygen that does not match its physiological levels in body tissues.
Also, cell differentiation status plays a role in the outcome of experiments. We
compared effects of 2 Gy X-ray irradiation on the physiology and mitochondrial
proteome of nondifferentiated and human neuroblastoma (SH-SY5Y) cells treated
with retinoic acid cultivated at 21% and 5% O2. Irradiation did not affect the
amount of subunits of OxPhos complexes and other non-OxPhos mitochondrial
proteins, except for heat shock protein 70, which was increased depending on
oxygen level and differentiation status. These two factors were proven to
modulate mitochondrial membrane potential and the bioenergetic status of cells.
We suggest, moreover, that oxygen plays a role in the differentiation of human SH
SY5Y cells.
PMID- 27615281
TI - Cranial Ontogeny of the Early Triassic Basal Cynodont Galesaurus planiceps.
AB - Ontogenetic changes in the skull and mandible of thirty-one specimens of
Galesaurus planiceps, a basal non-mammaliaform cynodont from the Early Triassic
of South Africa, are documented. The qualitative survey indicated eight changes
in the craniomandibular apparatus occurred during growth, dividing the sample
into three ontogenetic stages: juvenile, subadult, and adult. Changes in the
temporal region, zygomatic arch, occiput, and mandible occurred during the
transition from the subadult to adult stage at a basal skull length of 90 mm. At
least four morphological and allometric differences divided the adult specimens
into two morphs, indicating the presence of sexual dimorphism in Galesaurus.
Differences include extensive lateral flaring of the zygomatic arches in the
"male" morph resulting in a more anterior orientation of the orbits, and a
narrower snout in the "female". This is the first record of sexual dimorphism in
a basal cynodont, and the first time it is quantitatively documented in a non
mammaliaform cynodont. An ontogenetic comparison between Galesaurus and the more
derived basal cynodont Thrinaxodon revealed differences in the timing and extent
of sagittal crest development. In Galesaurus, the posterior sagittal crest,
located behind the parietal foramen, developed relatively later in ontogeny, and
the anterior sagittal crest rarely formed suggesting the anterior fibres of the
temporalis were less developed than in Thrinaxodon. In contrast, craniomandibular
features related to the masseters became more developed during the ontogeny of
Galesaurus. The development of the adductor musculature appears to be one of the
main factors influencing skull growth in these basal non-mammaliaform cynodonts.
Anat Rec, 300:353-381, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615282
TI - Lipoxin A4 selectively programs the profile of M2 tumor-associated macrophages
which favour control of tumor progression.
AB - In tumor microenvironments, the macrophage population is heterogeneous, but some
macrophages can acquire tumor-promoting characteristics. These tumor-associated
macrophages (TAM) exhibit an M2-like profile, with deficient production of NO and
ROS, characteristics of pro-inflammatory M1 cytotoxic macrophages. Lipoxins (LX)
and 15-epi-lipoxins are lipid mediators which can induce certain features of M2
macrophages in mononuclear cells, but their effects on TAM remain to be
elucidated. This study tested the hypothesis that ATL-1, a synthetic analogue of
15-epi-lipoxin A4 , could modulate TAM activity profile. We show that human
macrophages (MPhi) differentiated into TAM-like cells after incubation with
conditioned medium from MV3, a human melanoma lineage cell. Contrasting with the
effects observed in other M2 subsets and M1 profile macrophages, ATL-1
selectively decreased M2 surface markers in TAM, suggesting unique behavior of
this particular M2 subset. Importantly, these results were replicated by the
natural lipoxins LXA4 and the aspirin induced 15-epi-LXA4 (ATL). In parallel, ATL
1 stimulated TAM to produce NO by increasing the iNOS/arginase ratio and
activated NADPH oxidase, triggering ROS production. These alterations in TAM
profile induced by ATL-1 led to loss of the anti-apoptotic effects of TAM on
melanoma cells and increased their cytotoxic properties. Finally, ATL-1 was found
to inhibit tumor progression in a murine model in vivo, which was accompanied by
alterations in TAM profile and diminished angiogenesis. Together, the results
show an unexpected effect of lipoxin, which induces in TAM a change from an M2-
to an M1-like profile, thereby triggering tumor cell apoptosis and down
modulating the tumor progression.
PMID- 27615283
TI - Triple jeopardy for people with albinism.
PMID- 27615321
TI - Nematode parasites of four species of Carangoides (Osteichthyes: Carangidae) in
New Caledonian waters, with a description of Philometra dispar n. sp.
(Philometridae).
AB - Parasitological examination of marine perciform fishes belonging to four species
of Carangoides, i.e. C. chrysophrys, C. dinema, C. fulvoguttatus and C.
hedlandensis (Carangidae), from off New Caledonia revealed the presence of
nematodes. The identification of carangids was confirmed by barcoding of the COI
gene. The eight nematode species found were: Capillariidae gen. sp. (females),
Cucullanus bulbosus (Lane, 1916) (male and females), Hysterothylacium sp. third
stage larvae, Raphidascaris (Ichthyascaris) sp. (female and larvae), Terranova
sp. third-stage larvae, Philometra dispar n. sp. (male), Camallanus carangis
Olsen, 1954 (females) and Johnstonmawsonia sp. (female). The new species P.
dispar from the abdominal cavity of C. dinema is mainly characterised by the body
length (5.14 mm), the lengths of markedly unequal spicules (163 and 96 MUm) and
gubernaculum (102 MUm long) provided with a dorsal protuberance and a small,
reflexed dorsal barb on its posterior portion. The finding of C. bulbosus
represents the first record of this parasite a century after its discovery; the
first study of this species by scanning electron microscopy (SEM) enabled
detailed redescription. The finding of Johnstonmawsonia sp. in C. fulvoguttatus
is the first record of a rhabdochonid nematode from a host belonging to the
Carangidae family. Johnstonmawsonia africana Moravec & Puylaert, 1970 and J.
campanae Puylaert, 1973 are transferred to Prosungulonema Roytman, 1963 as P.
africanum (Moravec & Puylaert, 1970) comb. n. and P. campanae (Puylaert, 1973) n.
comb.
PMID- 27615323
TI - Increased mortality after lower extremity fractures in patients <65 years of age.
AB - Background and purpose - The association between mortality and lower extremity
fractures (other than hip fractures in older individuals) is unclear. We
therefore investigated mortality in adults of all ages after lower extremity
fractures that required inpatient care. Patients and methods - Diagnosis code
(ICD10), procedure code (NOMESCO), and 7 additional characteristics of patients
admitted to the trauma ward at Central Finland Hospital were collected between
2002 and 2008 (n = 3,567). Patients were followed up until the end of 2012.
Mortality rates were calculated for patients with all types of lower extremity
fractures using data from the population at risk. Results - During the study,
2,081 women and 1,486 men sustained a lower extremity fracture. By the end of
follow-up (mean duration 5 years), 42% of the women and 32% of the men had died.
For all lower extremity fractures, the standardized mortality ratio (SMR) was 1.9
(95% CI: 1.8-2.0) for women and 2.6 (CI: 2.4-2.9) for men. In patients aged >=65
years, mortality was increased and of similar magnitude after fractures of the
hip, femoral diaphysis, and knee (distal femur, patella, and proximal tibia). In
patients aged <65 years, mortality was increased after fractures at all sites.
The SMR after fractures at different sites ranged between 2.1 (CI: 1.4-3.2)
(ankle) and 6.7 (CI: 5.0-9.0) (hip) in patients aged <65 years and between 0.6
(CI: 0.30-1.1) (leg) and 2.2 (CI: 2.0-2.3) (hip) in patients aged >=65 years.
Interpretation - The post-fracture SMR of patients aged <65 years was at least
double that of older patients. Furthermore, the higher mortality observed after
proximal fractures of the lower extremity was greater in younger patients. The
reasons behind these findings remain unclear.
PMID- 27615325
TI - Are we prepared for high standards of trauma care?
AB - For some years emergency nurses have speculated about what a competent standard
of emergency nursing should look like. This is particularly important when
managing complex trauma cases. The Trauma Quality Improvement Network System
(TQuINS) was created to assess whether trauma care is safe and carried out by
practitioners proficient in dealing with complex cases (analysis, page 8 ).
PMID- 27615324
TI - Application of whole-exome sequencing to unravel the molecular basis of
undiagnosed syndromic congenital neutropenia with intellectual disability.
AB - Neutropenia can be qualified as congenital when of neonatal onset or when
associated with extra-hematopoietic manifestations. Overall, 30% of patients with
congenital neutropenia (CN) remain without a molecular diagnosis after a
multidisciplinary consultation and tedious diagnostic strategy. In the rare
situations when neutropenia is identified and associated with intellectual
disability (ID), there are few diagnostic hypotheses to test. This retrospective
multicenter study reports on a clinically heterogeneous cohort of 10 unrelated
patients with CN associated with ID and no molecular diagnosis prior to whole
exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The
results suggested that in many cases neutropenia and syndromic manifestations
could not be assigned to the same molecular alteration. Three sub-groups of
patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected
early in life, and related to a known mutation in the CN spectrum (ELANE); (ii)
mild to moderate benign intermittent neutropenia, detected later, and associated
with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1);
and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed
feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be
associated with a syndromic form of CN, the other reported mutations may not
explain the entire clinical picture. Although targeted gene sequencing can be
discussed for the primary diagnosis of severe CN, we suggest that performing WES
for the diagnosis of disorders associating CN with ID will not only provide the
etiological diagnosis but will also pave the way towards personalized care and
follow-up. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615326
TI - Nurses may replace doctors in EDs.
AB - Patients arriving at emergency departments (EDs) could be treated by specially
trained nurses instead of doctors as part of measures to tackle the 'crisis' in
emergency medicine.
PMID- 27615322
TI - Mutational signatures of ionizing radiation in second malignancies.
AB - Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage.
The signatures of mutations arising in human tissues following in vivo exposure
to ionizing radiation have not been documented. Here, we searched for signatures
of ionizing radiation in 12 radiation-associated second malignancies of different
tumour types. Two signatures of somatic mutation characterize ionizing radiation
exposure irrespective of tumour type. Compared with 319 radiation-naive tumours,
radiation-associated tumours carry a median extra 201 deletions genome-wide,
sized 1-100 base pairs often with microhomology at the junction. Unlike deletions
of radiation-naive tumours, these show no variation in density across the genome
or correlation with sequence context, replication timing or chromatin structure.
Furthermore, we observe a significant increase in balanced inversions in
radiation-associated tumours. Both small deletions and inversions generate driver
mutations. Thus, ionizing radiation generates distinctive mutational signatures
that explain its carcinogenic potential.
PMID- 27615327
TI - Emergency departments are 'buckling', warns RCN.
AB - The RCN has warned that emergency departments (EDs) in England are 'buckling'
under rising demand and a 'drastic shortage' of nurses.
PMID- 27615328
TI - Former nurse of the year wins praise for Safer Steps.
AB - Former RCN nurse of the year Amanda Burston will be recognised for her work
supporting victims of domestic abuse at an event celebrating the achievements of
women.
PMID- 27615329
TI - Study highlights CO poisoning.
AB - Emergency department (ED) nurses at Frimley Park Hospital in Surrey are taking
part in a study into how staff can detect and treat carbon monoxide (CO)
poisoning.
PMID- 27615331
TI - Clinicians suspend 'unsafe' emergency services for young people at Midlands
hospital.
AB - Emergency department (ED) services at a Midlands hospital have been suspended for
under-18s because senior clinicians have judged them unsafe.
PMID- 27615332
TI - Tougher nurse competencies set new standard for trauma centres.
AB - By the end of September, all emergency departments (EDs) that accept trauma
patients will have been assessed against rigorous new standards for nurse
knowledge and training.
PMID- 27615335
TI - Trial results make case for using acupuncture in pain relief.
AB - A randomised trial of 300 emergency department (ED) patients' responses to
titrated morphine or a half-hour acupuncture session was carried out.
PMID- 27615336
TI - Other scans.
PMID- 27615337
TI - Pressures on EDs rise as senior demographic increases.
AB - A Boston University School of Medicine trend assessment predicts steadily rising
pressure on emergency departments (EDs) as senior citizen numbers grow.
PMID- 27615338
TI - Sepsis.
AB - Essential facts [Figure: see text] Sepsis, a clinical syndrome caused by the
body's immune and coagulation systems being switched on by an infection, is
believed to cause about 44,000 deaths a year. If not recognised early and treated
promptly, sepsis can lead to shock, multiple organ failure and death. Major
reports (UK parliamentary and health service ombudsman enquiry in 2013 and the UK
National Confidential Enquiry into Patient Outcome and Death in 2015) have
highlighted sepsis as being a leading cause of avoidable death that kills more
people than breast, bowel and prostate cancer combined.
PMID- 27615339
TI - Avoiding mistaken epilepsy diagnosis in newborns.
AB - Parents of newborns can be reassured if healthcare professionals are aware of
benign neonatal sleep myoclonus (BNSM) so it is not mistaken for epilepsy.
PMID- 27615341
TI - Evernote app.
AB - [Figure: see text] For nurses who have meeting notes, to-do lists and reminders
spread across various devices, the Evernote app puts everything in one place.
PMID- 27615340
TI - Keeping the team happy.
AB - We are all aware of the increase in emergency activity in the past six months.
This, alongside failing social care resources, which significantly impacts the
ability of organisations to have 'flow', has created the perfect storm.
PMID- 27615342
TI - From twitter.
AB - Nurses on Twitter.
PMID- 27615343
TI - A tale of two proposals.
AB - This autumn, the United states will choose a new president and, with this, a
change in health care. Democratic candidate Hillary Clinton proposes the least
change, offering a public-option insurance plan and allowing Americans to enrol
in Medicare at 55.
PMID- 27615346
TI - Triad of death: the importance of temperature monitoring in trauma patients.
AB - Multiple organ failure is a significant complication in traumatic injury, and can
be exacerbated by a failure to adequately monitor and control trauma patients'
core body temperature in emergency departments (EDs). Nearly half of trauma
patients are hypothermic on arrival at emergency departments, often due to
factors beyond the control of emergency service responders and during on-scene
resuscitation attempts. This article examines the physiology of the 'triad of
death' -hypothermia, metabolic acidosis and coagulopathy - to highlight the
importance of monitoring and maintaining normothermia, or normal body
temperature, which is between 36 degrees C and 37.2 degrees C, in trauma patients
to improve outcomes. It also describes some rewarming interventions that can help
to save the lives of patients with multiple injuries. Major traumatic injury is
the leading cause of death in people under 40 years of age in the UK. Among major
trauma patients, 75% are male and 98% of injuries are caused by blunt force such
as falls or road traffic incidents ( National Institute for Health and Care
Excellence (NICE) 2015 ). The cost in terms of lost economic output is variously
estimated to be between L3.3 billion ( National Audit Office 2010 ) and L3.7
billion a year ( Scott 2016 ). Multiple organ failure is a significant
complication of traumatic injury, and is exacerbated by failure to adequately
monitor and control the patient's core body temperature in ED. On arrival at ED,
43% of trauma patients are hypothermic ( Allen et al 2010 ), often due to factors
beyond the control of emergency service responders, such as complicated
extrications in adverse environmental conditions. Initial resuscitative attempts
on-scene can further reduce core body temperature, because of prolonged exposure
to the environment and administration of cold intravenous (IV) fluids ( Duchesne
et al 2010 ).
PMID- 27615347
TI - Lactate in the emergency department: a case-based critical reflection.
AB - Serum lactate levels are frequently measured in patients with undifferentiated
conditions in emergency departments. This article uses a case-based reflection to
critically analyse the role of lactate measurement in these patients. It examines
the rationale for testing, and the potential causes of raised levels, to remind
clinicians that this diagnostic intervention must be taken in the context of
patients' clinical presentations and not in isolation.
PMID- 27615348
TI - Recognition and management of seizures in children in emergency departments.
AB - Seizure is defined as 'a sudden surge of electrical activity in the brain, which
usually affects how a person appears or acts for a short time'. Children who have
experienced seizures commonly present to emergency departments (EDs), and
detailed history taking will usually help differentiate between epileptic and non
epileptic events. ED nurses are often the first health professionals to manage
children with seizures, and this is best done by following the ABCDE approach.
Treatment involves termination of seizures with anticonvulsants, and children may
need other symptomatic management. Seizures in children can be an extremely
distressing experience for parents, who should be supported and kept informed by
experienced ED nurses. Nurses also play a vital role in educating parents on
correct administration of anticonvulsants and safety advice. This article
discusses the aetiology, clinical presentation, diagnosis and management of
children with seizures, with particular emphasis on epilepsy. It includes two
reflective case studies to highlight the challenges faced by healthcare
professionals managing children who present with convulsions.
PMID- 27615349
TI - Testing the limits of skills, knowledge and resolve.
AB - Why did you become an emergency nurse? I was fortunate when I was a student to
have a placement in St Thomas' emergency department (ED) and I had a great mentor
who made it an exciting learning environment, so I had my eye on the ED back
then.
PMID- 27615350
TI - Online.
AB - 'You have to know how to work with influence; as a director of nursing you may
not have the operational clout or the budgetary control but working effectively
through the power of influence is your art'.
PMID- 27615351
TI - Calculating drug doses.
AB - Numeracy and calculation are key skills for nurses. As nurses are directly
accountable for ensuring medicines are prescribed, dispensed and administered
safely, they must be able to understand and calculate drug doses.
PMID- 27615352
TI - Spirituality and holistic care.
AB - National and international professional health and nursing guidelines recommend
that attention should be given to the spiritual and religious needs of patients.
This suggests that spiritual care is an important aspect of holistic patient care
that needs to be considered and supported, if relevant, in a healthcare context.
PMID- 27615353
TI - In other RCNi journals.
AB - 'The use of technology to support communication in therapy is an exciting
development, particularly the use of mobile device emojis to help young people
express, and practitioners to assess, their mental distress. However, there is
limited research on the subject and some possible drawbacks to its use in
practice'.
PMID- 27615354
TI - Discharging older patients.
AB - Significant numbers of older people with dementia use general hospital services,
and ensuring the safe and appropriate discharge home of patients with poor
cognition, impaired judgement, misperception or reduced risk awareness is complex
and challenging for many healthcare professionals.
PMID- 27615356
TI - Combined acute inhalation of hydrofluoric acid and nitric acid: a case report and
literature review.
AB - We describe a nonlethal, delayed onset case of combined acute inhalation of
hydrofluoric acid (HFA) and nitric acid (NA) together with a review of the
literature. Our patient was exposed to fumes of a 12% HFA and 22% NA solution in
a closed environment and suffered during several months after the incident from
exertional dyspnoea but recovered completely. Since HFA and NA are dangerous and
widely used substances, preparedness for exposure is mandatory. After
inhalational exposure, the principles of decontamination with attention to
treatment of the skin for HFA burns together with general medical incident
management should be applied. The severity of combined NA and HFA intoxication
depends on the concentration, the nature of the contact and the duration of
exposure but other factors may also be involved. Therapy resistant hypoxia and
death have been reported in the literature. Inhalation injury from HFA alone is
rare but systemic toxicity should be anticipated. Calcium is advocated as the
cornerstone of local and systemic therapy. NA inhalation alone is very rare and
causes heavy pulmonary irritation. Massive pulmonary secretions seem a sign of
very severe intoxication and treatment appears to be mainly supportive.
PMID- 27615357
TI - Combining diffusion magnetic resonance tractography with stereology highlights
increased cross-cortical integration in primates.
AB - The isocortex of primates is disproportionately expanded relative to many other
mammals, yet little is known about what the expansion of the isocortex entails
for differences in cellular composition and connectivity patterns in primates.
Across the depth of the isocortex, neurons exhibit stereotypical patterns of
projections. Upper-layer neurons (i.e., layers II-IV) project within and across
cortical areas, whereas many lower-layer pyramidal neurons (i.e., layers V-VI)
favor connections to subcortical regions. To identify evolutionary changes in
connectivity patterns, we quantified upper (i.e., layers II-IV)- and lower (i.e.,
layers V-VI)-layer neuron numbers in primates and other mammals such as rodents
and carnivores. We also used MR tractography based on high-angular resolution
diffusion imaging and diffusion spectrum imaging to compare anterior-to-posterior
corticocortical tracts between primates and other mammals. We found that primates
possess disproportionately more upper-layer neurons as well as an expansion of
anterior-to-posterior corticocortical tracts compared with other mammals. Taken
together, these findings demonstrate that primates deviate from other mammals in
exhibiting increased cross-cortical connectivity. J. Comp. Neurol. 525:1075-1093,
2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615358
TI - Grain Boundary Induced Bias Instability in Soluble Acene-Based Thin-Film
Transistors.
AB - Since the grain boundaries (GBs) within the semiconductor layer of organic field
effect transistors (OFETs) have a strong influence on device performance, a
substantial number of studies have been devoted to controlling the
crystallization characteristics of organic semiconductors. We studied the
intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene
(TES-ADT) thin films on the electrical properties of OFETs. The GB density was
easily changed by controlling nulceation event in TES-ADT thin films. When the
mixing time was increased, the number of aggregates in as-spun TES-ADT thin films
were increased and subsequent exposure of the films to 1,2-dichloroethane vapor
led to a significant increase in the number of nuleation sites, thereby
increasing the GB density of TES-ADT spherulites. The density of GBs strongly
influences the angular spread and crystallographic orientation of TES-ADT
spherulites. Accordingly, the FETs with higher GB densities showed much poorer
electrical characteristics than devices with lower GB density. Especially, GBs
provide charge trapping sites which are responsible for bias-stress driven
electrical instability. Dielectric surface treatment with a polystyrene brush
layer clarified the GB-induced charge trapping by reducing charge trapping at the
semiconductor-dielectric interface. Our study provides an understanding on GB
induced bias instability for the development of high performance OFETs.
PMID- 27615359
TI - Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense
Capacity.
AB - Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide
for which the radiation exposure is the most influential risk factor. The levels
of oxidative stress in PTC are not well characterized on the tissue level. The
objective of this study was to evaluate total oxidant status (TOS) and total
antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine
their association with clinicopathological characteristics. Tumor and normal
thyroid tissue samples were collected from 59 PTC patients, and goiter tissues
were collected from 50 BG patients. TOS and TAS were quantified in the tissue
homogenates by spectrophotometric assays. TOS values in tumor tissues did not
differ significantly from normal and goiter tissues; however, PTC tissues have
significantly higher TAS values than normal and goiter tissues. TOS values
correlated with retrosternal growth in BG patients. The significant correlations
were found between TOS and TAS values and thyroid function parameters. In 17 PTC
patients with multiple tumor foci (multicentric phenotype), TAS values were
significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are
the most useful predictors of thyroid capsular invasion by PTC. The age, sex,
body mass index, smoking, familial history of thyroid disease and nodule size did
not influence TOS and TAS in PTC or BG patients. In conclusion, we show the
profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess
increased antioxidant capacity. The redox status influences the parameters of the
thyroid function and tumor's biological behavior.
PMID- 27615355
TI - Characterization of a Fetal Liver Cell Population Endowed with Long-Term
Multiorgan Endothelial Reconstitution Potential.
AB - Stable reconstitution of vascular endothelial beds upon transplantation of
progenitor cells represents an important challenge due to the paucity and
generally limited integration/expansion potential of most identified vascular
related cell subsets. We previously showed that mouse fetal liver (FL)
hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell
Leukaemia (SCL) gene enhancer transgene (SCL-PLAP+ cells), had robust endothelial
engraftment potential when transferred to the blood stream of newborns or adult
conditioned recipients, compared to the scarce vascular contribution of adult
bone marrow cells. However, the specific SCL-PLAP+ hematopoietic or endothelial
cell subset responsible for the long-term reconstituting endothelial cell (LTR
EC) activity and its confinement to FL developmental stages remained unknown.
Using a busulfan-treated newborn transplantation model, we show that LTR-EC
activity is restricted to the SCL-PLAP+ VE-cadherin+ CD45- cell population,
devoid of hematopoietic reconstitution activity and largely composed by Lyve1+
endothelial-committed cells. SCL-PLAP+ Ve-cadherin+ CD45- cells contributed to
the liver sinusoidal endothelium and also to the heart, kidney and lung
microvasculature. LTR-EC activity was detected at different stages of FL
development, yet marginal activity was identified in the adult liver, revealing
unknown functional differences between fetal and adult liver
endothelial/endothelial progenitors. Importantly, the observations that expanding
donor-derived vascular grafts colocalize with proliferating hepatocyte-like cells
and participate in the systemic circulation, support their functional integration
into young livers. These findings offer new insights into the engraftment,
phonotypical, and developmental characterization of a novel
endothelial/endothelial progenitor cell subtype with multiorgan LTR-EC activity,
potentially instrumental for the treatment/genetic correction of vascular
diseases. Stem Cells 2017;35:507-521.
PMID- 27615360
TI - Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a
high incidence setting: a retrospective population-based study in East Greenland.
AB - In East Greenland, a dramatic increase of tuberculosis (TB) incidence has been
observed in recent years. Classical genotyping suggests a genetically similar
Mycobacterium tuberculosis (Mtb) strain population as cause, however, precise
transmission patterns are unclear. We performed whole genome sequencing (WGS) of
Mtb isolates from 98% of culture-positive TB cases through 21 years (n = 182)
which revealed four genomic clusters of the Euro-American lineage (mainly sub
lineage 4.8 (n = 134)). The time to the most recent common ancestor of lineage
4.8 strains was found to be 100 years. This sub-lineage further diversified in
the 1970s, and massively expanded in the 1990s, a period of lowered TB awareness
in Greenland. Despite the low genetic strain diversity, WGS data revealed several
recent short-term transmission events in line with the increasing incidence in
the region. Thus, the isolated setting and the uniformity of circulating Mtb
strains indicated that the majority of East Greenlandic TB cases originated from
one or few strains introduced within the last century. Thereby, the study shows
the consequences of even short interruptions in TB control efforts in previously
TB high incidence areas and demonstrates the potential role of WGS in detecting
ongoing micro epidemics, thus guiding public health efforts in the future.
PMID- 27615361
TI - An Update on Canine, Feline and Bovine Papillomaviruses.
AB - Over recent years, a growing number of papillomaviruses have been identified,
which cause a wide range of lesions in domestic and wild animals. Papillomavirus
induced lesions may have a great impact on animal health, and some diseases
observed in farm animals are associated with significant economic losses. This
concise review brings together recent advancements on animal papillomavirus
research, providing the scientific community and veterinary practitioners with an
update on this rapidly evolving field. Among others, bovine, canine and feline
papillomaviruses (BPV, CPV and FcaPV) are most extensively discussed, in view of
the recent discovery of new viral types and their worldwide importance for animal
health. Feline papillomaviruses 2 is an emerging, highly prevalent pathogen in
domestic cats, associated with a subset of malignant skin lesions. Aspects
related to cross-species infection by BPV and its environmental co-factors are
also addressed. Animal papillomaviruses are also fascinating models for studying
molecular and cell biology and have recently inspired some major breakthroughs.
Overall, it is clear that additional, international and systematic efforts are
needed to clarify which lesions are caused by which viral types and to develop
experimental models for studying animal papillomavirus.
PMID- 27615362
TI - Modulating peripheral nerve damage from hyperglycemia/anoxia.
AB - INTRODUCTION: Combined hyperglycemia and anoxia have a marked negative effect on
peripheral nerve not seen with either alone. We studied whether nerve injury is
related to the presence of hyperglycemia in the oxygenated state, anoxic state,
or both. METHODS: We performed recordings of the nerve action potential (NAP)
from rat sciatic nerve in a perfusion apparatus with different metabolic
substrates during anoxia and oxygenated state. RESULTS: The NAP was best
preserved when one of the perfusates contained no glucose. Transient improvements
were seen with normoglycemic perfusates or perfusates that contained substrates
that were poorly used in glycolysis/gluconeogenesis. Hyperglycemia has important
negative effects in both the oxygenated and anoxic states. CONCLUSIONS:
Deleterious effects of hyperglycemia on the peripheral nerve may relate to
metabolic products produced during the oxygenated state, such as glycogen and the
effects of reperfusion after prolonged periods of anoxic metabolism. Muscle
Nerve, 2016 Muscle Nerve 55: 735-740, 2017.
PMID- 27615363
TI - Small bowel anisakiasis detected by capsule endoscopy.
PMID- 27615364
TI - Design and demonstration of an intracortical probe technology with tunable
modulus.
AB - Intracortical probe technology, consisting of arrays of microelectrodes, offers a
means of recording the bioelectrical activity from neural tissue. A major
limitation of existing intracortical probe technology pertains to limited
lifetime of 6 months to a year of recording after implantation. A major
contributor to device failure is widely believed to be the interfacial mechanical
mismatch of conventional stiff intracortical devices and the surrounding brain
tissue. We describe the design, development, and demonstration of a novel
functional intracortical probe technology that has a tunable Young's modulus from
~2 GPa to ~50 MPa. This technology leverages advances in dynamically softening
materials, specifically thiol-ene/acrylate thermoset polymers, which exhibit
minimal swelling of < 3% weight upon softening in vitro. We demonstrate that a
shape memory polymer-based multichannel intracortical probe can be fabricated,
that the mechanical properties are stable for at least 2 months and that the
device is capable of single unit recordings for durations up to 77 days in vivo.
This novel technology, which is amenable to processes suitable for manufacturing
via standard semiconductor fabrication techniques, offers the capability of
softening in vivo to reduce the tissue-device modulus mismatch to ultimately
improve long term viability of neural recordings. (c) 2016 Wiley Periodicals,
Inc. J Biomed Mater Res Part A: 105A: 159-168, 2017.
PMID- 27615366
TI - Establishment of mouse Mac-2 binding protein enzyme-linked immunosorbent assay
and its application for mouse chronic liver disease models.
AB - AIM: We identified Mac-2 (galectin-3) binding protein (Mac-2bp) as a novel
diagnostic and liver fibrosis predicting biomarker for nonalcoholic
steatohepatitis in humans. In mouse models, there are no serum biomarkers
predicting liver disease severity. In this study, we developed a mouse Mac-2bp
enzyme-linked immunosorbent assay (ELISA) system and determined its efficacy for
predicting the severity of liver disease in mouse models, especially in non
alcoholic fatty liver disease (NAFLD) models. METHODS: We established several rat
monoclonal antibodies against mouse Mac-2bp, selected two clones for the ELISA,
and checked the accuracy and reproducibility of the ELISA, especially for NAFLD
models and liver fibrosis models. We also investigated the relationships between
serum levels and hepatic gene expression of Mac-2bp in mouse models. RESULTS: Our
ELISA system had high accuracy and reproducibility (R2 = 0.999). The intra-assay
and inter-assay results for the coefficient of variation were 2.0-3.7% and 1.7
6.9%, respectively. The levels of bilirubin, hemoglobin, and chyle did not affect
the Mac-2bp serum levels detected by our ELISA kit. In the mouse models, serum
Mac-2bp levels increased with liver disease progression (F0/F1/F2/F3, 239.1 +/-
36.7 / 259.1 +/- 43.0 / 457.5 +/- 162.0 / 643.7 +/- 116.0 ng/mL; P < 0.0001), and
were significantly correlated with hepatic gene expression of Mac-2bp (R = 0.42,
P < 0.0001). CONCLUSION: Our mouse Mac-2bp ELISA system effectively predicts
severity of NAFLD and liver fibrosis in mouse models.
PMID- 27615365
TI - Effect of X-ray irradiation on ancient DNA in sub-fossil bones - Guidelines for
safe X-ray imaging.
AB - Sub-fossilised remains may still contain highly degraded ancient DNA (aDNA)
useful for palaeogenetic investigations. Whether X-ray computed [micro-]
tomography ([MU]CT) imaging of these fossils may further damage aDNA remains
debated. Although the effect of X-ray on DNA in living organisms is well
documented, its impact on aDNA molecules is unexplored. Here we investigate the
effects of synchrotron X-ray irradiation on aDNA from Pleistocene bones. A clear
correlation appears between decreasing aDNA quantities and accumulating X-ray
dose-levels above 2000 Gray (Gy). We further find that strong X-ray irradiation
reduces the amount of nucleotide misincorporations at the aDNA molecule ends. No
representative effect can be detected for doses below 200 Gy. Dosimetry shows
that conventional MUCT usually does not reach the risky dose level, while
classical synchrotron imaging can degrade aDNA significantly. Optimised
synchrotron protocols and simple rules introduced here are sufficient to ensure
that fossils can be scanned without impairing future aDNA studies.
PMID- 27615367
TI - Dynamics of surface evolution in semiconductor thin films grown from a chemical
bath.
AB - Dynamics of surface evolution in CdS thin films grown by chemical bath deposition
technique has been studied from time sequence of atomic force micrographs.
Detailed scaling analysis of surface fluctuation in real and Fourier space
yielded characteristic exponents alphaloc = 0.78 +/- 0.07, alpha = 2.20 +/- 0.08,
alphas = 1.49 +/- 0.22, beta = 0.86 +/- 0.05 and betaloc = 0.43 +/- 0.10, which
are very different from those predicted by the local growth models and are not
related to any known universality classes. The observed anomalous scaling
pattern, characterized by power law scaling dependence of interface width on
deposition time differently at local and global scale, with rapid roughening of
the growth front has been discussed to arise as a consequence of a nonlocal
effect in the form of diffusional instability.
PMID- 27615368
TI - Nutrition: Folic acid delays CKD progression.
PMID- 27615369
TI - First step to investigate nature of electronic states and transport in flower
like MoS2: Combining experimental studies with computational calculations.
AB - In the present paper, the nature of electronic states and transport properties of
nanostructured flower-like molybdenum disulphide grown by hydrothermal route has
been studied. The band structure, electronic nature of charge, thermodynamics and
the limit of phonon scattering through density functional theory (DFT) has also
been studied. The band tail states, dynamics of trap states and transport of
carriers was investigated through intensive impedance spectroscopy analysis. The
direct fingerprint of density and band tail state is analyzed from the
capacitance plot as capacitance reflects the capability of a semiconductor to
accept or release the charge carriers with a corresponding change in its Fermi
potential levels. A recently introduced infrared photo-carrier radiometry and
density functional perturbation theory (DFPT) techniques have been used to
determine the temperature dependence of carrier mobility in flower type-MoS2. The
present study illustrates that a large amount of trapped charges leads to an
underestimation of the measured effective mobility and the potential of the
material. Thus, a continuous engineering effort is required to improve the
quality of fabricated nanostructures for its potential applications.
PMID- 27615370
TI - Design methodology for a confocal imaging system using an objective microlens
array with an increased working distance.
AB - In this study, a design methodology for a multi-optical probe confocal imaging
system was developed. To develop an imaging system that has the required
resolving power and imaging area, this study focused on a design methodology to
create a scalable and easy-to-implement confocal imaging system. This system
overcomes the limitations of the optical complexities of conventional multi
optical probe confocal imaging systems and the short working distance using a
micro-objective lens module composed of two microlens arrays and a telecentric
relay optical system. The micro-objective lens module was fabricated on a glass
substrate using backside alignment photolithography and thermal reflow processes.
To test the feasibility of the developed methodology, an optical system with a
resolution of 1 MUm/pixel using multi-optical probes with an array size of 10 *
10 was designed and constructed. The developed system provides a 1 mm * 1 mm
field of view and a sample scanning range of 100 MUm. The optical resolution was
evaluated by conducting sample tests using a knife-edge detecting method. The
measured lateral resolution of the system was 0.98 MUm.
PMID- 27615371
TI - The dynamic nature of crystal growth in pores.
AB - The kinetics of crystal growth in porous media controls a variety of natural
processes such as ore genesis and crystallization induced fracturing that can
trigger earthquakes and weathering, as well as, sequestration of CO2 and toxic
metals into geological formations. Progress on understanding those processes has
been limited by experimental difficulties of dynamically studying the reactive
surface area and permeability during pore occlusion. Here, we show that these
variables cause a time-dependency of barite growth rates in microporous silica.
The rate is approximately constant and similar to that observed on free surfaces
if fast flow velocities predominate and if the time-dependent reactive surface
area is accounted for. As the narrower flow paths clog, local flow velocities
decrease, which causes the progressive slowing of growth rates. We conclude that
mineral growth in a microporous media can be estimated based on free surface
studies when a) the growth rate is normalized to the time-dependent surface area
of the growing crystals, and b) the local flow velocities are above the limit at
which growth is transport-limited. Accounting for the dynamic relation between
microstructure, flow velocity and growth rate is shown to be crucial towards
understanding and predicting precipitation in porous rocks.
PMID- 27615372
TI - A novel method for the injection and manipulation of magnetic charge states in
nanostructures.
AB - Realising the promise of next-generation magnetic nanotechnologies is contingent
on the development of novel methods for controlling magnetic states at the
nanoscale. There is currently demand for simple and flexible techniques to access
exotic magnetisation states without convoluted fabrication and application
processes. 360 degrees domain walls (metastable twists in magnetisation
separating two domains with parallel magnetisation) are one such state, which is
currently of great interest in data storage and magnonics. Here, we demonstrate a
straightforward and powerful process whereby a moving magnetic charge, provided
experimentally by a magnetic force microscope tip, can write and manipulate
magnetic charge states in ferromagnetic nanowires. The method is applicable to a
wide range of nanowire architectures with considerable benefits over existing
techniques. We confirm the method's efficacy via the injection and spatial
manipulation of 360 degrees domain walls in Py and Co nanowires. Experimental
results are supported by micromagnetic simulations of the tip-nanowire
interaction.
PMID- 27615373
TI - Increased perceived stress is related to decreased prefrontal cortex volumes
among older adults.
AB - INTRODUCTION: Several of the brain regions vulnerable to increased levels of
stress (i.e., hippocampus and prefrontal cortex) are also known to undergo
disproportionate decline during normal aging. To date, surprisingly little
research has examined the effects of stress on the brain among healthy human
populations, much less in the elderly. The aim of the current study was to
investigate the relationship between chronic stress and brain morphometry in
regions known for their involvement in the stress response, namely the prefrontal
cortex, hippocampus, and amygdala, in a sample of healthy older adults. METHOD:
The Perceived Stress Scale and structural magnetic resonance imaging (MRI) were
collected in 28 older adult individuals aged 65 to 90 years. Gray and white
matter volumes in various regions of interest in the prefrontal cortex and medial
temporal lobes were calculated using semiautomated segmentation tools. RESULTS:
Perceived stress was negatively correlated with overall prefrontal cortex (PFC)
volume, specifically in overall white matter volume of the PFC. Additionally,
perceived stress was negatively correlated with gray and white matter volumes in
lateral regions of the PFC, specifically, in the ventrolateral and dorsolateral
PFC. Perceived stress was not significantly related to medial temporal lobe
volumes. CONCLUSIONS: These findings suggest that among healthy older adults,
there is a salient relationship between prefrontal cortex volumes and levels of
perceived stress. This research fills a critical gap in the current literature
and provides initial groundwork for future studies investigating the relationship
between perceived stress and the prefrontal cortex in the context of healthy
aging.
PMID- 27615374
TI - Nano spin-diodes using FePt-NDs with huge on/off current ratio at room
temperature.
AB - Spin transistors have attracted tremendous interest as new functional devices.
However, few studies have investigated enhancements of the ON/OFF current ratio
as a function of the electron spin behavior. Here, we found a significantly high
spin-dependent current ratio-more than 10(2) at 1.5 V-when changing the relative
direction of the magnetizations between FePt nanodots (NDs) and the CoPtCr-coated
atomic force microscope (AFM) probe at room temperature. This means that ON and
OFF states were achieved by switching the magnetization of the FePt NDs, which
can be regarded as spin-diodes. The FePt magnetic NDs were fabricated by exposing
a bi-layer metal stack to a remote H2 plasma (H2-RP) on ~1.7 nm SiO2/Si(100)
substrates. The ultrathin bi-layers with a uniform surface coverage are changed
drastically to NDs with an areal density as high as ~5 * 10(11) cm(-2). The FePt
NDs exhibit a large perpendicular anisotropy with an out-of-plane coercivity of
~4.8 kOe, reflecting the magneto-crystalline anisotropy of (001) oriented L10
phase FePt. We also designed and fabricated double-stacked FePt-NDs with low and
high coercivities sandwiched between an ultra-thin Si-oxide interlayer, and
confirmed a high ON/OFF current ratio when switching the relative magnetization
directions of the low and high coercivity FePt NDs.
PMID- 27615376
TI - Evolutionary change in physiological phenotypes along the human lineage.
AB - BACKGROUND AND OBJECTIVES: Research in evolutionary medicine provides many
examples of how evolution has shaped human susceptibility to disease. Traits
undergoing rapid evolutionary change may result in associated costs or reduce the
energy available to other traits. We hypothesize that humans have experienced
more such changes than other primates as a result of major evolutionary change
along the human lineage. We investigated 41 physiological traits across 50
primate species to identify traits that have undergone marked evolutionary change
along the human lineage. METHODOLOGY: We analysed the data using two Bayesian
phylogenetic comparative methods. One approach models trait covariation in non
human primates and predicts human phenotypes to identify whether humans are
evolutionary outliers. The other approach models adaptive shifts under an
Ornstein-Uhlenbeck model of evolution to assess whether inferred shifts are more
common on the human branch than on other primate lineages. RESULTS: We identified
four traits with strong evidence for an evolutionary increase on the human
lineage (amylase, haematocrit, phosphorus and monocytes) and one trait with
strong evidence for decrease (neutrophilic bands). Humans exhibited more cases of
distinct evolutionary change than other primates. CONCLUSIONS AND IMPLICATIONS:
Human physiology has undergone increased evolutionary change compared to other
primates. Long distance running may have contributed to increases in haematocrit
and mean corpuscular haemoglobin concentration, while dietary changes are likely
related to increases in amylase. In accordance with the pathogen load hypothesis,
human monocyte levels were increased, but many other immune-related measures were
not. Determining the mechanisms underlying conspicuous evolutionary change in
these traits may provide new insights into human disease.
PMID- 27615375
TI - Decreased PD-1 Expression on CD8 Lymphocyte Subsets and Increase in CD8 Tscm
Cells in Children with HIV Receiving Raltegravir.
AB - We investigated the effect of combination antiretroviral therapy (cART) on immune
recovery, particularly on the percentages of PD-1-positive cells within the major
leukocyte subsets. Cryopreserved peripheral blood mononuclear cells and plasma
samples collected longitudinally from a subset of 13 children and adolescents
(between 9.7 and 18.2 years old) who were enrolled in the International Maternal
Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 were used for this
study. Immunophenotyping by flow cytometry was performed to determine the effect
of raltegravir-containing cART regimen on the distribution of leukocyte
populations, on the expression of PD-1 on T cell subpopulations, and on the
expression of well-established markers of T cell activation (CD38 and HLA-DR) on
CD8 T cells. C reactive protein (CRP), lipopolysaccharide (LPS), IL-6, and
soluble CD163 were assayed in plasma samples by an enzyme-linked immunosorbent
assay. Plasma viral loads were decreased in all subjects (by an average of 2.9
log units). The cART regimen, including raltegravir, induced changes in CD8 T
cell subsets, consistent with an effective antiretroviral outcome and improved
immunologic status, including increased percentages of CD8 stem cell memory T
cells (Tscm). The percentages of CD8 PD-1-positive cells decreased significantly
as compared with baseline levels. Among the proinflammatory markers measured in
plasma, sCD163 showed a decline that was associated with cART. cART therapy,
including raltegravir, over 48 weeks in children is associated with immune
restoration, consistent with effective antiretroviral therapy, namely decreased
percentages of PD-1+ CD8+ T cells, an increase in CD8 Tscm cells, and decreased
levels of sCD163.
PMID- 27615377
TI - Oestrogen upregulates the expression levels and functional activities of duodenal
mucosal CFTR and SLC26A6.
AB - NEW FINDINGS: What is the central question of this study? Duodenal ulcer is a
common disease. A sex-based difference in the incidence of duodenal ulcer has
long been observed clinically, but the cause is unclear. What is the main finding
and its importance? Duodenal mucosal bicarbonate secretion is the most important
protective factor in duodenal mucosa against acid-induced damage. The cystic
fibrosis transmembrane conductance regulator (CFTR) and the solute-linked carrier
26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that
mediate duodenal mucosal bicarbonate secretion. We demonstrate that endogenous
oestrogen upregulates the expression levels and functional activities of duodenal
mucosal CFTR and SLC26A6, which contributes to the sex difference in the
prevalence of duodenal ulcer. The incidence of duodenal ulcer is markedly lower
in women than men, but the cause of the sex difference is not clear. The cystic
fibrosis transmembrane conductance regulator (CFTR) and the solute-linked carrier
26 gene family A6 (SLC26A6) are two key bicarbonate transport proteins that
mediate duodenal mucosal bicarbonate secretion, which is an important protective
factor against acid-induced duodenal injury. The aim of this study was to
investigate the effect of oestrogen on the expressions and functional activities
of CFTR and SLC26A6 in duodenal mucosa. We found that the expression levels of
duodenal CFTR and SLC26A6 were markedly higher in young (20- to 30-year-old)
women than in young men and old (60- to 70-year-old) women and men. The
expression levels of CFTR and SLC26A6 in young women were markedly higher in
preovulatory phases than in premenstrual phases, which was consistent with the
changes of serum estradiol concentrations. Further results showed that duodenal
CFTR and SLC26A6 expression levels in female mice were markedly decreased after
ovariectomy, and supplementation with estradiol reversed the changes in CFTR and
SLC26A6. 17beta-Estradiol increased CFTR and SLC26A6 expression levels of human
duodenocytes in experiments in vitro. Functional experiments showed that basal
and forskolin- and prostaglandin E2 -stimulated duodenal bicarbonate secretion in
ovariectomized mice was markedly decreased and, likewise, supplementation with
17beta-estradiol reversed the changes. In conclusion, endogenous oestrogen
upregulates the expressions and functional activities of CFTR and SLC26A6 in
duodenal mucosa, which could contribute to protection of the duodenum and explain
the sex difference in the prevalence of duodenal ulcer.
PMID- 27615378
TI - Risk factors and treatment for steroid-related mood and behavior symptoms in
preschool children with leukemia: A case series.
AB - Treatment of pediatric acute lymphoblastic leukemia (ALL) relies on systemic
corticosteroids for remission; however, they can cause significant mood and
behavior changes that interfere with quality of life and may increase risk for
injury. This case series reports on preschool children with preexisting
developmental and psychiatric risk factors who presented with behavioral side
effects that required intervention. Identification of these vulnerable children
may provide opportunities for early intervention, anticipatory guidance, and
effective treatment to minimize behavioral side effects and improve quality of
life and safety during ALL treatment.
PMID- 27615379
TI - Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated
with poor prognosis.
AB - Lactate dehydrogenase A (LDHA), a key metabolic enzyme, plays a crucial role in
the final step of anaerobic glycolysis. Overexpression of LDHA is observed in
many human malignancies in association with tumor progression. The purpose of
this study was to investigate LDHA expression pattern during carcinogenesis, its
clinico-pathological association, and evaluate the prognostic value of LDHA in
CCA patients. LDHA expression was investigated using immunohistochemistry
technique in both hamster- (n=60) and human-CCA tissues (n=82). Plasma LDH from
healthy control (n=40) and CCA patients (n=29) were determined using an enzymatic
based assay. The association of LDHA expression with clinico-pathological
findings and prognostic value were evaluated by statistical analysis. In the CCA
hamster model, an increase of LDHA expression was associated with the progression
of CCA-genesis. Higher LDHA overexpression was associated with shorter survival
of CCA patients. Multivariate analysis indicated that LDHA expression including
histological type and N stage of tumor were independent prognostic risk factor of
patient's survival. However, there was no difference in plasma LDH level between
CCA patients and healthy controls. LDHA expression is involved in
cholangiocarcinogenesis. Overexpression of LDHA can be a marker of poor prognosis
in CCA patients and it might be a potential target for CCA treatment.
PMID- 27615380
TI - Mitochondrial hyperpolarization and cytochrome-c release in microwave-exposed MCF
7 cells.
AB - This study examines the effects of a 2.1-GHz WCDMA-modulated microwave (MW)
radiation on apoptotic activity and mitochondrial membrane potential (DeltaPsim)
in MCF-7 cells. The cells were exposed to the MW at a specific absorption rate
(SAR) of 0.528 W/kg for 4 or 24 h. The antiproliferative effect of MW exposure
was determined by the MTT test. Cytochrome-c and p53 levels were determined by an
ELISA method. The relative DeltaPsim was analysed by JC-1 staining using flow
cytometer. Apoptotic rate of the cells was measured by Annexin-V-FITC staining.
All assays were performed after certain time of incubations (15 min-4 h)
following MW exposure. MW-exposed cells showed a significant decrease in
viability when compared to unexposed cells. A significantly larger decrease was
observed after longer exposure. The percentage of apoptotic cells, amount of
cytochrome-c, and relative DeltaPsim were significantly higher in MW-exposed
cells. The percent of apoptotic cells and relative DeltaPsim in 24 h MW-exposed
group was significantly higher than those in 4 h MW-exposed group. However, no
significant change was observed in p53 levels. These results demonstrated that
exposure to 2.1-GHz WCDMA-modulated MW radiation caused hyperpolarization of
mitochondria that in turn induced apoptosis in MCF-7 cells.
PMID- 27615382
TI - Engineering Surfaces through Sequential Stop-Flow Photopatterning.
AB - Solution-exchange lithography is a new modular approach to engineer surfaces via
sequential photopatterning. An array of lenses reduces features on an inkjet
printed photomask and reproduces arbitrarily complex patterns onto surfaces. In
situ exchange of solutions allows successive photochemical reactions without
moving the substrate and affords access to hierarchically patterned substrates.
PMID- 27615383
TI - Established and emerging targeted therapies in the myelodysplastic syndromes.
AB - INTRODUCTION: Therapy for the myelodysplastic syndromes (MDS) is an evolving area
of research which has made significant use of the increased understanding of the
complex biology of these disorders. Novel agents targeting multiple pathogenic
pathways are being actively tested in preclinical and clinical settings and hold
the potential to be available to clinicians before long. AREAS COVERED: Herein we
provide an historical framework for understanding the current use of
hypomethylating agents in MDS and discuss recent developments in the field of
targeted therapy in MDS including data from published and ongoing clinical
studies with oral hypomethylating agents, PI3/polo-like kinase inhibitors, TGF
beta inhibitor/ligand traps, and immune checkpoint inhibitors. A comprehensive
review of recent literature was undertaken using PubMed and Medline. Expert
commentary: Management of MDS patients will evolve substantially in the near
future with the incorporation of molecular data into patient stratification
models and with the introduction of novel targeted agents.
PMID- 27615381
TI - Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is
cell-type-specific.
AB - Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative
disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading
to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is
ubiquitously expressed and therefore nuclear inclusions could be present in all
brain cells. The effects of nuclear inclusion formation have been mainly studied
in neurons, while the effect on glia has been comparatively disregarded.
Astrocytes, microglia, and oligodendrocytes are glial cells that are essential
for normal brain function and are implicated in several neurological diseases.
Here we examined the number of nuclear mHTT inclusions in both neurons and
various types of glia in the two brain areas that are the most affected in HD,
frontal cortex, and striatum. We compared nuclear mHTT inclusion body formation
in three HD mouse models that express either full-length HTT or an N-terminal
exon1 fragment of mHTT, and we observed nuclear inclusions in neurons,
astrocytes, oligodendrocytes, and microglia. When studying the frequency of cells
with nuclear inclusions in mice, we found that half of the population of neurons
contained nuclear inclusions at the disease end stage, whereas the proportion of
GFAP-positive astrocytes and oligodendrocytes having a nuclear inclusion was much
lower, while microglia hardly showed any nuclear inclusions. Nuclear inclusions
were also present in neurons and all studied glial cell types in human patient
material. This is the first report to compare nuclear mHTT inclusions in glia and
neurons in different HD mouse models and HD patient brains. GLIA 2016;65:50-61.
PMID- 27615384
TI - Ectopic position of duplicated KIT gene in African Nguni cattle, associated with
color sidedness, confirms its shared ancestry with the Bos taurus lineage.
PMID- 27615385
TI - Short-term benefits of an unrestricted-calorie traditional Mediterranean diet,
modified with a reduced consumption of carbohydrates at evening, in overweight
obese patients.
AB - The Mediterranean diet (MeD) is believed to promote health; nevertheless, changes
in the nutritional patterns in the Mediterranean area (increased intake of
refined carbohydrates/saturated fats; reduced fibers intake; main calorie load
shifted to dinner) led to reduced MeD benefits in recent decades. We
retrospectively investigated the effects of a MeD with a low intake of refined
carbohydrates in the evening ("MeDLowC") on body weight (BW) and metabolic
profile of overweight/obese subjects. According to their adherence to MeDLowC,
subjects were classified into 44 (41%) individuals with "excellent" adherence and
63 (59%) with "poor" adherence. Nutritional counseling induced an improvement in
BW, glucose metabolism and liver transaminases in both groups, with an increased
magnitude of these effects in the "Excellent" adherence group. "Excellent"
adherence to MeDLowC improved insulin sensitivity and lipid metabolism. In
conclusion, MeD with a restriction of carbohydrates in the evening significantly
ameliorates obesity and associated metabolic complications.
PMID- 27615386
TI - Pharmacologic treatment of the ovarian endometrioma.
AB - INTRODUCTION: Treatment of ovarian endometriomas is commonly achieved through
laparoscopic surgery and this can be effective in eliminating the disease,
although a majority of recent trials documented an adverse effect of surgery on
ovarian reserve markers. With the advancement in imaging techniques, ovarian
endometriomas are increasingly diagnosed at an earlier stage when the
endometrioma may be smaller, less fibrotic and more responsive to medical
treatment, making an evaluation of medical options critically important. AREAS
COVERED: The review focuses on currently utilized pharmacologic therapies for
endometrioma (oral contraceptives, the levonorgestrel-releasing IUS, the hormone
releasing subdermal implant, Implanon); experimental and future treatments are
also mentioned (GnRH antagonists, progesterone receptor modulators,
antioestrogens, newer subdermal implants and intracystic administration of
pharmacologic agents). Finally, the usefulness of post-operative adjuvant medical
treatments is discussed Expert opinion: Today, reliable, non-invasive diagnostic
procedures of an ovarian endometrioma are available and should be utilized to
identify its presence and type of pathology. In a young patient, classic medical
therapies such as oral contraceptives and synthetic progestins should be tried
first to alleviate symptoms. Only when these regimens fail, should a minimally
invasive surgery be envisaged. Following endoscopic surgery, adjuvant medical
treatment may reduce recurrence of both symptoms and the lesion.
PMID- 27615387
TI - The Arabidopsis MIEL1 E3 ligase negatively regulates ABA signalling by promoting
protein turnover of MYB96.
AB - The phytohormone abscisic acid (ABA) regulates plant responses to various
environmental challenges. Controlled protein turnover is an important component
of ABA signalling. Here we show that the RING-type E3 ligase MYB30-INTERACTING E3
LIGASE 1 (MIEL1) regulates ABA sensitivity by promoting MYB96 turnover in
Arabidopsis. Germination of MIEL1-deficient mutant seeds is hypersensitive to
ABA, whereas MIEL1-overexpressing transgenic seeds are less sensitive. MIEL1 can
interact with MYB96, a regulator of ABA signalling, and stimulate its
ubiquitination and degradation. Genetic analysis shows that MYB96 is epistatic to
MIEL1 in the control of ABA sensitivity in seeds. While MIEL1 acts primarily via
MYB96 in seed germination, MIEL1 regulates protein turnover of both MYB96 and
MYB30 in vegetative tissues. We find that ABA regulates the expression of MYB30
responsive genes during pathogen infection and this regulation is partly
dependent on MIEL1. These results suggest that MIEL1 may facilitate crosstalk
between ABA and biotic stress signalling.
PMID- 27615388
TI - Preoperative Antibiotics Do Not Reduce Postoperative Infections Following Needle
Localized Lumpectomy.
AB - Many surgeons routinely use a single preoperative prophylactic dose of an
antibiotic prior to needle-localized lumpectomy, despite the lack of evidence
that this practice reduces the rate of infection. The aim of this study is to
determine if antibiotic administration reduces wound infection for needle
localized lumpectomy. A retrospective chart review of patients that underwent
needle-localized lumpectomy from 2010 to 2012 was conducted. Data regarding
patient demographics, comorbid conditions, medical history, operative details,
and pathology were collected. Surgical infections requiring opening of the wound
or treatment with antibiotics were documented if occurred during the first 3
months following surgery. Fisher's exact tests were used for statistical
analyses. Two hundred and twenty patients were identified. Thirty-six percent
(80/220) of patients received preoperative prophylactic antibiotics. The
antibiotic and the nonantibiotic group were similar in age, body mass index,
tobacco use, history of radiation, history of neo-adjuvant chemotherapy, duration
of surgery, duration needle in place, and pathology. Two percent (4/220) of
patients had wound infections. Two percent (3/140) of patients in the
nonantibiotic group had infections, versus 1% (1/80) in the antibiotic group. In
an analysis of patients that developed infections (n = 4) and patients that did
not (n = 216), there was no statistically significant difference in patient
demographic, duration of surgery, duration of time needle in place, or pathology.
It is safe to omit the use of antibiotics prior to needle-localized lumpectomy
and avoid the cost of the medication, patient adverse reactions, and increase in
resistant organisms.
PMID- 27615389
TI - Caring for cancer survivors: perspectives of oncologists, general practitioners
and patients in Italy.
AB - AIM: The present survey investigates the views of medical oncologists, general
practitioners (GPs) and patients about the various surveillance strategies.
METHODS: An online survey was conducted in Italy on a population of 329 medical
oncologists, 380 GPs and 350 patients. RESULTS: Most of GPs (n = 291; 76%) claim
that follow-up should be provided by the collaboration between GPs and medical
oncologists. Most medical oncologists report to have a poor relationship with GPs
(n = 151; 46%) or no relationships at all (n = 14; 4%). Most patients believe
there is no real collaboration between medical oncologists and GPs (n = 138;
54%). CONCLUSION: GPs, medical oncologists and patients share the idea that the
collaboration between oncologists and GPs for surveillance of cancer survivors is
poor and should be improved.
PMID- 27615390
TI - Tau and tauopathies.
AB - Most neurodegenerative diseases are characterized by intracellular aggregates of
insoluble proteins. As for the majority of these disorders, aetiology and
pathogenesis are only poorly understood; current nosological concepts are largely
based on these molecular signatures of protein aggregates which also provide
valuable tools for neuropathological differential diagnosis. The microtubule
associated protein tau is one of these proteins that form intracellular
fibrillary deposits in neurons and glial cells of a large variety of disorders
today collectively referred to as tauopathies. While dysfunction of tau has
unequivocally been shown to be able to cause neurodegeneration, the precise
mechanisms of how tau is involved in neurodegenerative disorders is still poorly
understood. After research has focused for several decades on the axonal function
of tau and on the fibrillar tau aggregation, more recent cell biological studies
have opened up new insights into the role of tau at the synapse and in the
nucleus. According to currently emerging cell biological concepts, tau might play
a role in the regulation of neuronal plasticity in a wide array of neuronal
networks. In addition, it might be involved in regulating genome stability. The
most intriguing question relevant both to physiological and pathophysiological
function of tau is the biological meaning of the large heterogeneity of isoforms
of tau which apparently is a rather promiscuous molecule. The present review is
divided into two parts. First, we give an overview on the molecular biology and
cell biology of tau and its physiological functions. The second part deals with
the pathophysiology of tau and description of tauopathies which comprise more
than 20 disorders including Alzheimer's disease, progressive supranuclear palsy,
cortico basal degeneration, Pick's disease and others.
PMID- 27615391
TI - Effects of chlorogenic acid on voltage-gated potassium channels of trigeminal
ganglion neurons in an inflammatory environment.
AB - Chlorogenic acid (CGA) composed of coffee acid and quinic acid is an effective
ingredient of many foods and medicines and widely exhibits biological effects.
Recently, it is reported to have analgesic effect. However, little is known about
the analgesic mechanism of CGA. In this study, whole-cell patch-clamp recordings
were performed on two main subtypes (IK,A and IK,V channels) of voltage-gated
potassium (KV) channels in small-diameter(<30MUm) trigemianl ganglion neurons to
analyze the effects of CGA in an inflammatory environment created by
Prostaglandin E2 (PGE2). On one hand, the activation and inactivation V1/2 values
of IK,A and IK,V channels showed an elevation towards a depolarizing shift caused
by PGE2. On the other hand, the activation and inactivation V1/2 values of the
two channels had a reduction towards a hyperpolarizing shift caused by CGA under
PGE2 pretreatment. Our results demonstrated that CGA may exhibited an analgesic
effect by promoting KV channels activation and inactivation under inflammatory
condition, which provided a novel molecular and ionic mechanism underlying anti
inflammatory pain of CGA.
PMID- 27615393
TI - Combining ptychographical algorithms with the Hybrid Input-Output (HIO)
algorithm.
AB - In this article we combine the well-known Ptychographical Iterative Engine (PIE)
with the Hybrid Input-Output (HIO) algorithm. The important insight is that the
HIO feedback function should be kept strictly separate from the reconstructed
object, which is done by introducing a separate feedback function per probe
position. We have also combined HIO with floating PIE (fPIE) and extended PIE
(ePIE). Simulations indicate that the combined algorithm performs significantly
better in many situations. Although we have limited our research to a combination
with HIO, the same insight can be used to combine ptychographical algorithms with
any phase retrieval algorithm that uses a feedback function.
PMID- 27615392
TI - Mutant p53: a novel target for the treatment of patients with triple-negative
breast cancer?
AB - The identification and validation of a targeted therapy for patients with triple
negative breast cancer (TNBC) is currently one of the most urgent needs in breast
cancer therapeutics. One of the key reasons for the failure to develop a new
therapy for this subgroup of breast cancer patients has been the difficulty in
identifying a highly prevalent, targetable molecular alteration in these tumors.
Recently however, the p53 gene was found to be mutated in approximately 80% of
basal/TNBC, raising the possibility that targeting the mutant p53 protein product
might be a new approach for the treatment of this form of breast cancer. In this
study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1MET (APR
246), two compounds which were previously reported to reactivate mutant p53 and
convert it to a form with wild-type (WT) properties. Using a panel of 18 breast
cancer cell lines and 2 immortalized breast cell lines, inhibition of
proliferation by PRIMA-1 and PRIMA-1MET was found to be cell-line dependent, but
independent of cell line molecular subtype. Although response was independent of
molecular subtype, p53 mutated cell lines were significantly more sensitive to
PRIMA-1MET than p53 WT cells (p = 0.029). Furthermore, response (measured as IC50
value) correlated significantly with p53 protein level as measured by ELISA (p =
0.0089, r=-0.57, n = 19). In addition to inhibiting cell proliferation, PRIMA
1MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner.
Based on our data, we conclude that targeting mutant p53 with PRIMA-1MET is a
potential new approach for treating p53-mutated breast cancer, including the
subgroup with triple-negative (TN) disease.
PMID- 27615394
TI - Resonance frequencies of AFM cantilevers in contact with a surface.
AB - To make the forces in an Atomic Force Microscope that operates in a dynamic mode
with one or multiple vibrations applied to the cantilever, quantitative, one
needs to relate a change in resonance frequency of the cantilever to a specific
tip-sample interaction. Due to the time dependence of the force between the tip
and sample caused by the vibrations, this task is not only difficult, but in fact
only possible to solve for certain limiting cases, if one follows common
theoretical approaches with a Taylor expansion around the deflection point. Here,
we present an analytical method for calculating the resonance frequencies of the
cantilever that is valid for any tip-sample interaction. Instead of linearizing
the tip-sample interaction locally, we calculate an averaged, weighted
linearization taking into account all positions of the tip while vibrating. Our
method bridges, therefore, the difficult gap between a free oscillating
cantilever and a cantilever that is pushed infinitely hard into contact with a
surface, which describes a clamped-pinned boundary condition. For a correct
description of the cantilever dynamics, we take into account both the tip mass
and the tip moment of inertia. Applying our model, we show that it is possible to
calculate the modal response of a cantilever as a function of the tip-sample
interaction strength. Based on these modal vibration characteristics, we show
that the higher resonance frequencies of a cantilever are completely insensitive
to the strength of the tip-sample interaction.
PMID- 27615395
TI - The Nordic Consortium for Acute type A Aortic Dissection (NORCAAD): objectives
and design.
AB - OBJECTIVES: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) is
a collaborative effort of Nordic cardiac surgery centers to study acute type A
aortic dissection (ATAAD). Here, we outline the overall objectives and the design
of NORCAAD. DESIGN: NORCAAD currently consists of eight centers in Denmark,
Finland, Iceland and Sweden. Data was collected for patients undergoing surgery
for ATAAD from 2005 to 2014. A total of 194 variables were retrospectively
collected including demographics, past medical history, preoperative medications,
symptoms at presentation, operative variables, complications, bleeding and blood
transfusions, need for late reoperations, 30-day mortality and long-term
survival. RESULTS: Information was gathered in the database for 1159 patients, of
which 67.6% were male. The mean age was 61.5 +/- 12.1 years. The mean follow-up
was 3.1 +/- 2.9 years with a total of 3535 patient years. CONCLUSIONS: NORCAAD
provides a foundation for close collaboration between cardiac surgery centers in
the Nordic countries. Substudies in progress include: short-term outcomes, long
term survival, time interval from diagnosis until operation, effects of surgical
techniques, malperfusion syndrome, renal failure, bleeding and neurological
complications on outcomes and the rate of late reoperations.
PMID- 27615396
TI - Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma.
AB - INTRODUCTION: The incidence rate of lung adenocarcinoma (LUAD), the predominant
histological subtype of lung cancer, is elevated in Asians, particularly in
female nonsmokers. The mutation patterns in LUAD in Asians might be distinct from
those in LUAD in whites. METHODS: We profiled 271 resected LUAD tumors (mainly
stage I) to characterize the genomic landscape of LUAD in Asians with a focus on
female nonsmokers. RESULTS: Mutations in EGFR, KRAS, erb-b2 receptor tyrosine
kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma
receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met
Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in
LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those
reported in studies of LUAD in non-Asians. In addition, we identified a novel
mutational signature of XNX (the mutated base N in the middle flanked by two
identical bases at the 5' and 3' positions) that was overrepresented in LUAD
tumors in nonsmokers and negatively correlated with the overall mutational
frequency. CONCLUSIONS: In this cohort, approximately 85% of individuals have
known driver mutations (EGFR 59.4%, KRAS 7.4%, ALK 7.4%, ERBB2 2.6%, ROS1 2.2%,
RET 2.2%, MET 1.8%, BRAF 1.1%, and NRAS 0.4%). Seventy percent of smokers and 90%
of nonsmokers had defined oncogenic drivers matching the U.S. Food and Drug
Administration-approved targeted therapies.
PMID- 27615398
TI - Preoperative predictors of delay in initiation of adjuvant chemotherapy in
patients undergoing primary debulking surgery for ovarian cancer.
AB - OBJECTIVE: The objective of this study was to identify preoperative
characteristics of patients that experience a delay in initiation of adjuvant
chemotherapy after primary debulking surgery for ovarian cancer.
MATERIALS/METHODS: We performed a retrospective review of patients with Stage II
to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who
underwent primary debulking surgery followed by adjuvant chemotherapy from 2005
to 2013. Patients were divided into 2 groups: Control (those who received their
first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy
delay (those who received their first cycle of chemotherapy at an interval
>6weeks from primary debulking surgery). Relevant clinical variables and survival
outcomes were compared between the 2 groups using standard statistical methods.
RESULTS: A total of 221 patients were included in the analyses - 169 (76.5%) were
in the control group and 52 (23.5%) were in the chemo delay group. On multi
variate analysis, risk factors that were significantly associated with a delay in
initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted
Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated
with a shorter progression-free (p=0.014) but not overall survival (p=0.19).
CONCLUSIONS: Delay in initiation of chemotherapy affected 23.5% of patients in
our study population. Easily identifiable risk factors for chemotherapy delay
exist that can help us pre-operatively identify patients for which neoadjuvant
chemotherapy may be a better treatment option. Further study into prospective
modeling with these identified risk factors is warranted.
PMID- 27615397
TI - Autoantibody Signature Enhances the Positive Predictive Power of Computed
Tomography and Nodule-Based Risk Models for Detection of Lung Cancer.
AB - INTRODUCTION: The incidence of pulmonary nodules is increasing with the movement
toward screening for lung cancer by low-dose computed tomography. Given the large
number of benign nodules detected by computed tomography, an adjunctive test
capable of distinguishing malignant from benign nodules would benefit
practitioners. The ability of the EarlyCDT-Lung blood test (Oncimmune Ltd.,
Nottingham, United Kingdom) to make this distinction by measuring autoantibodies
to seven tumor-associated antigens was evaluated in a prospective registry.
METHODS: Of the members of a cohort of 1987 individuals with Health Insurance
Portability and Accountability Act authorization, those with pulmonary nodules
detected, imaging, and pathology reports were reviewed. All patients for whom a
nodule was identified within 6 months of testing by EarlyCDT-Lung were included.
The additivity of the test to nodule size and nodule-based risk models was
explored. RESULTS: A total of 451 patients (32%) had at least one nodule, leading
to 296 eligible patients after exclusions, with a lung cancer prevalence of 25%.
In 4- to 20-mm nodules, a positive test result represented a greater than twofold
increased relative risk for development of lung cancer as compared with a
negative test result. Also, when the "both-positive rule" for combining binary
tests was used, adding EarlyCDT-Lung to risk models improved diagnostic
performance with high specificity (>92%) and positive predictive value (>70%).
CONCLUSIONS: A positive autoantibody test result reflects a significant increased
risk for malignancy in lung nodules 4 to 20 mm in largest diameter. These data
confirm that EarlyCDT-Lung may add value to the armamentarium of the practitioner
in assessing the risk for malignancy in indeterminate pulmonary nodules.
PMID- 27615399
TI - Extended mortality results for ovarian cancer screening in the PLCO trial with
median 15years follow-up.
AB - BACKGROUND: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening
Trial originally reported no mortality benefit of ovarian cancer screening after
a median of 12.4years of follow-up. The UKCTOCS screening trial failed to show a
statistically significant mortality reduction in the primary analysis but
reported an apparent increased mortality benefit in trial years 7-14 compared to
0-7. Here we report an updated analysis of PLCO with extended mortality follow
up. METHODS: Participants were randomized from 1993 to 2001 at ten U.S. centers
to an intervention or usual care arm. Intervention arm women were screened for
ovarian cancer with annual trans-vaginal ultrasound (TVU) (4years) and CA-125
(6years), with a fixed cutoff at 35U/mL for CA-125. The original follow-up period
was for up to 13years (median follow-up 12.4years); in this analysis follow-up
for mortality was extended by up to 6years. RESULTS: 39,105 (intervention) and
39,111 (usual care) women were randomized, of which 34,253 and 34,304,
respectively, had at least one ovary at baseline. Median follow-up was 14.7years
in each arm and maximum follow-up 19.2years in each arm. A total of 187
(intervention) and 176 (usual care) deaths from ovarian cancer were observed, for
a risk-ratio of 1.06 (95% CI: 0.87-1.30). Risk-ratios were similar for study
years 0-7 (RR=1.04), 7-14 (RR=1.06) and 14+ (RR=1.09). The risk ratio for all
cause mortality was 1.01 (95% CI: 0.97-1.05). Ovarian cancer specific survival
was not significantly different across trial arms (p=0.16). CONCLUSION: Extended
follow-up of PLCO indicated no mortality benefit from screening for ovarian
cancer with CA-125 and TVU.
PMID- 27615401
TI - Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food
choice and extended-access cocaine intake in male rhesus monkeys.
AB - BACKGROUND: Clinical trial data suggest amphetamine treatment is most efficacious
in moderate to high frequency cocaine users. However, preclinical studies have
examined amphetamine treatment effects under relatively limited cocaine access
conditions with low to moderate cocaine intakes. This study determined d
amphetamine treatment effects on cocaine self-administration in rhesus monkeys
under cocaine access conditions allowing for high daily cocaine intake. For
comparison and as a negative control, treatment effects with the antipsychotic
risperidone were also examined. METHODS: Continuous 21-day treatments with
ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h,
i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15
21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily
access to two types of cocaine self-administration sessions: (1) a 2-h 'choice'
session with concurrent availability of 1-g food pellets and intravenous cocaine
injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session
with 0.1mg/kg per injection cocaine availability. RESULTS: Total daily cocaine
intake increased >6-fold during extended cocaine access. d-Amphetamine
significantly decreased total cocaine intake, but not cocaine vs food choice. In
contrast, risperidone did not significantly alter either total cocaine intake or
cocaine vs. food choice. CONCLUSIONS: These results confirm and extend previous
results supporting treatment effectiveness for monoamine releasers, but not
dopamine antagonists, to reduce cocaine self-administration. Moreover, these
results suggest amphetamine treatment efficacy to decrease preclinical cocaine
vs. food choice may depend upon cocaine access conditions.
PMID- 27615402
TI - Does the familial transmission of drinking patterns persist into young adulthood?
A 10-year follow up.
AB - BACKGROUND: Parental drinking has been shown to be associated with offspring
drinking. However, the relationship appears to be more complex than often assumed
and few studies have tracked it over longer time periods. AIMS: To explore the
long-term (10-year) transmission of familial drinking during adolescence to
offspring drinking patterns in young adulthood. DESIGN: Swedish longitudinal
study, assessing the relationship between familial drinking in 2000 and offspring
drinking in 2010 using simultaneous quantile regression analysis (n=744). DATA:
Data on familial drinking was gathered from the Swedish level-of-living surveys
(LNU) and from partner LNU in 2000 while data on offspring drinking in young
adulthood was gathered from LNU 2010. Drinking among offspring, parents and
potential stepparents was measured through identical quantity-frequency indices
referring to the past 12 months in 2010 and 2000 respectively. RESULTS: Young
adults whose families were abstainers in 2000 drank substantially less across
quintiles in 2010 than offspring of non-abstaining families. The difference,
however, was not statistically significant between quintiles of the conditional
distribution. Actual drinking levels in drinking families were not at all or
weakly associated with drinking in offspring. Supplementary analyses confirmed
these patterns. CONCLUSION: The association between familial drinking and
offspring drinking in young adulthood exhibits clear non-linear trends. Changes
in the lower part of the familial drinking distribution are strongly related to
drinking in young adults, but the actual levels of drinking in drinking families
appear less important in shaping the drinking patterns of the offspring in young
adulthood.
PMID- 27615400
TI - Melanoma central nervous system metastases: current approaches, challenges, and
opportunities.
AB - Melanoma central nervous system metastases are increasing, and the challenges
presented by this patient population remain complex. In December 2015, the
Melanoma Research Foundation and the Wistar Institute hosted the First Summit on
Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania.
Here, we provide a review of the current status of the field of melanoma brain
metastasis research; identify key challenges and opportunities for improving the
outcomes in patients with melanoma brain metastases; and set a framework to
optimize future research in this critical area.
PMID- 27615404
TI - Reply to Letter to the Editor: 'Complex regional pain syndrome: Measurement
matters'.
PMID- 27615403
TI - Behavioral risk assessment for infectious diseases (BRAID): Self-report
instrument to assess injection and noninjection risk behaviors in substance
users.
AB - BACKGROUND: Infectious diseases such as Human Immunodeficiency Virus and
Hepatitis C are a significant problem among substance abusers. Current risk
behavior measures [e.g., HIV Risk Taking Behaviour Scale (HRBS) and Risk
Assessment Battery (RAB)] were developed for injection drug users and do not
include newly identified risks or noninjection drug use behaviors. This study
developed and provided initial, internal validation of the Behavioral Risk
Assessment for Infectious Diseases (BRAID) to assess infectious disease risk
behaviors among alcohol and other drug users. METHODS: A self-report measure was
developed from literature regarding risk behaviors. Participants (total N=998)
with alcohol/substance use disorder completed the measure in 2 phases to
establish initial psychometric validity. RESULTS: Phase 1 (N=270) completed 65
self-report questions; factor analysis revealed a 12-item solution with 5 factors
(Unprotected Sex with Risky Partners, Injection Use, Sex on Cocaine/Crack, Condom
Availability, and Intranasal Drug Use). Infectious disease history was positively
associated with Injection Use (Sample 1) and Unprotected Sex with Risky Partners
(Sample 2) and negatively associated with Intranasal Drug Use (Samples 1 and 2).
Phase 2 (N=728) added additional injection-related items and confirmed the factor
structure of the existing BRAID. CONCLUSIONS: The BRAID is a 5-factor, 14-item
self-report measure of past 6 month risk behaviors that is composed of
noninjection and injection risk behaviors and was psychometrically confirmed.
Though additional external (convergent/divergent) validation is needed, this
report provides preliminary support for the use of the BRAID to assess infectious
disease risk in substance users.
PMID- 27615405
TI - Levels, profiles and dietary sources of hydroxylated PCBs and hydroxylated and
methoxylated PBDEs in Japanese women serum samples.
AB - Human exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl
ethers (PBDEs) may result in retention of specific congeners of hydroxylated PCBs
(OH-PCBs) and hydroxylated/methoxylated PBDEs (OH-/MeO-PBDEs) in serum. However,
dietary sources and biotransformation of OH-/MeO-PBDEs in humans are poorly
understood. Therefore, this study was conducted to investigate the levels,
profiles, and exposure sources of OH-/MeO-PBDEs along with OH-PCBs present in
human serum. Twenty serum samples pooled from women of four age groups
(30s/40s/50s/60s) living in four districts of Japan were analyzed for OH-/MeO
PBDEs, and their profiles were then compared with those of seafood (seaweed and
fish). The major component of OH-PCBs in the phenolic fraction of serum was 4-OH
CB187 (mean: 85pgg-1 wet weight (ww)). Total OH-PCBs accounted for about 1/20 of
the total PCBs (mean; 1800pgg-1 ww). In contrast, the predominant component of OH
PBDEs in serum was 6-OH-BDE47 (mean: 183pgg-1 ww), which was about 20-fold higher
than BDE-47 (mean; 8.7pgg-1 ww). In the neutral fraction, 2'-MeO-BDE68 was
primarily found at a similar concentration (mean 5.6pgg-1 ww) to BDE-47. Both 4
OH-PCB187 and 2'-MeO-BDE68 were significantly correlated with woman's age
(p<0.01), but not with 6-OH-BDE47 or BDE-47. The profiles of OH-PBDEs in serum
were consistent with those in edible seaweeds (Sargassum fusiforme) sold for
human consumption, whereas MeO-PBDEs had a similar profile as those in edible
fish (Serranidae sp.) from Japanese coastal waters. These findings indicate that
the profiles of OH-PBDEs and MeO-PBDEs in Japanese serum are different from those
in other countries, and their sources may be specific edible seaweeds and fish,
respectively. This is the first report of profiles and dietary sources of OH/MeO
PBDEs in human serum from Japan.
PMID- 27615406
TI - Hippocampal neuronal degeneration in the traumatic brain injury mouse: non
trivial effect of scalp incision.
AB - OBJECTIVES: In experimental models of traumatic brain injury (TBI), posttraumatic
hippocampal neuronal degeneration in the cornu ammonis 1 (CA1), and/or the cornu
ammonis 3 (CA3) regions are regarded as the most notable phenotypic appearances
relating to the pathophysiology of human post-concussion syndrome. However, these
morphological changes are often also seen in subjects without TBI, namely 'sham'
groups. The frequencies and reasons of appearance of hippocampal neuronal
degeneration in mice with TBI and/or sham are not clear. METHODS: We compared the
frequencies of hippocampal neuronal degeneration among three groups: TBI (mice
with external force impact performed by Marmarou's weight drop model after scalp
incision), sham (mice with scalp incision alone), and control (mice with neither
external force impact nor scalp incision), using hematoxylin and eosin stain in
day 6 (n = 5 in each group.) Isoflurane was used for anesthesia in all mice.
RESULTS: The frequencies were 80, 100, and 20% in CA1, and 20, 40, and 60% in
CA3, for TBI, sham, and control, respectively. In CA1, a significant difference
of the frequency was observed between sham and control (p = 0.048), but not,
between TBI and sham (p = 1.000) in Fisher's exact test. In CA3, no significant
difference in the frequency was observed between the three groups. CONCLUSION:
Scalp incision, rather than external impact force, might affect the CA1
hippocampal neuronal degeneration in mice with TBI. In addition, factor(s) other
than external impact force or scalp incision may also cause hippocampal neuronal
degeneration in both CA1 and CA3. Careful interpretation is needed concerning
hippocampal neuronal degeneration induced by a weight drop device observed in
mice with TBI.
PMID- 27615407
TI - Marfan syndrome: Report of a complex phenotype due to a 15q21.1 contiguos gene
deletion encompassing FBN1, and literature review.
AB - Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that
primarily involves skeletal, ocular, and cardiovascular systems with large inter-
and intra-familial variability in terms of age of onset, severity, and aortic
disease. The causal gene, FBN1, encodes for fibrillin 1, a multi-domain
glycoprotein essential for many biological functions, including deposition and
formation of elastic fibers. Reports describing chromosomal alterations involving
FBN1 are rare, but in the last years their number has increased after copy number
state analyses, such as multiplex ligation-dependent probe amplification and
microarray-based comparative genomic hybridization, were adopted as routine
diagnostic tools. Herein we report a patient with MFS and an atypical facial
appearance and neuropsychiatric involvement likely not attributable to MFS due to
a 15q21.1 deletion that involves part of FBN1 and 13 additional contiguous genes
listed in OMIM. We compare his phenotype with those of the few patients described
in the literature who share similar 15q11.2 deletions. This report expands the
phenotype of patients with 15q11.2 deletion involving FBN1 and its contiguous
genes, and suggests a possible role for these other genes in the pathogenesis of
the observed unusual clinical signs that are not explained by FBN1
haploinsufficiency. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615408
TI - Alterations in l-arginine metabolism in first-episode schizophrenia patients:
Further evidence for early metabolic dysregulation.
PMID- 27615409
TI - A longitudinal study of adolescent psychotic experiences and later development of
substance use disorder and suicidal behavior.
AB - INTRODUCTION: Psychotic experiences are associated with later substance use
disorder and suicidal behavior, but individual psychotic experiences have not
been examined in a longitudinal data set. Also, the potential dose-response
relationship between these phenomena remains unknown. METHOD: Cohort study
including 9242 adolescents who participated in The Child and Adolescent Twin
Study in Sweden (CATSS). At ages 15 and/or 18, seven psychotic experiences
(auditory and visual hallucinations, and five delusions) were assessed via
questionnaires. Outcomes at follow-up were physician-assigned diagnoses of
substance use disorder and suicide attempts ascertained from the Swedish Patient
Register. Associations were estimated with Cox regressions and expressed as
hazard ratios. RESULTS: All psychotic experiences were associated with later
substance use disorder and/or suicide attempts, with hazard ratios ranging from
1.6 to 3.0. A dose-response relationship was observed between psychotic
experiences and later substance use disorder, and suicide attempt. DISCUSSION:
Auditory and visual hallucinations as well as delusions in adolescence are
associated with later development of substance use disorder and suicide attempt,
and there is a dose-response relationship between the load of psychotic
experiences and these adverse outcomes. Clinicians should assess subclinical
hallucinations as well as delusions in psychiatric evaluations of adolescents.
PMID- 27615410
TI - Reply.
PMID- 27615411
TI - Pirfenidone in patients with rapidly progressive interstitial lung disease
associated with clinically amyopathic dermatomyositis.
AB - To evaluate the efficacy of pirfenidone in patients with rapidly progressive
interstitial lung disease (RPILD) related to clinically amyopathic
dermatomyositis (CADM), we conducted an open-label, prospective study with
matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a
disease duration <6 months at Renji Hospital South Campus from June 2014 to
November 2015 were prospectively enrolled and treated with pirfenidone at a
target dose of 1800 mg/d in addition to conventional treatment, such as a
glucocorticoid and/or other immunosuppressants. Matched patients without
pirfenidone treatment (n = 27) were retrospectively selected as controls between
October 2012 and September 2015. We found that the pirfenidone add-on group
displayed a trend of lower mortality compared with the control group (36.7% vs
51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the
pirfenidone add-on had no impact on the survival of acute ILD patients (disease
duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients
(disease duration 3-6 months), the pirfenidone add-on (n = 10) had a
significantly higher survival rate compared with the control subgroup (n = 9)
(90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may
improve the prognosis of patients with subacute ILD related to CADM.
PMID- 27615412
TI - Immunohistochemical Localization of Somatostatin in the Brain of Chinese
Alligator Alligator sinensis.
AB - In this study, the regional distribution and histological localization of
somatostatin (SS) immunoreactive (IR) perikarya and fibers was investigated for
the first time in the brain of adult Chinese alligator by immunohistochemical
method. The results showed SS-IR perikarya and fibers were widely distributed in
various parts of the brain except for olfactory bulbs. In the telencephalon, SS
IR perikarya were predominantly located in the cellular layer and deep plexiform
layer of dorsomedial and medial cortex, less in the dorsal and lateral cortex,
while SS-IR fibers were found in all layers of the cerebral cortex. SS-IR
perikarya and fibers were also detected in the dorsal ventricular ridge,
hippocampus cortex, accessory olfactory bulb nuclearus, lenticular nucleus, and
caudate nucleus. In the diencephalon, SS-IR perikarya and fibers were mainly
present in supraoptic nucleus, paraventricular nucleus of hypothalamus, recessus
infundibular nucleus, median eminence, the pineal gland and pituitary gland, in
which the IR-fibers were abundant, appearing dot-shaped and varicosity-like. In
the mesencephalon, they were present in tectum cortex, ependyma of cerebral
aqueduct and the periaqueductal grey matter. Additionally, they were also
detected in Purkinje's cellular layer of cerebellum, in the reticularis nucleus
and raphe nucleus of medulla oblongata. The distribution pattern of SS-IR
perikarya and fibers in the brain of Chinese alligator is generally similar to
that reported in other reptiles, but also has some specific features. The wide
distribution indicated that SS might be a neurotransmitter or neuromodulator
which acts on many kinds of target cells with a wide range of physiological
functions. Anat Rec, 300:507-519, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615413
TI - Effect of parameters on the quality of core-shell fibrous scaffold for retinal
differentiation of conjunctiva mesenchymal stem cells.
AB - This article describes the coaxial electrospinning to generate core-shell fibers
from polycaprolactone (PCL) and polyethylene glycol (PEG) for differentiation of
conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells by
delivery of taurine. Also, the effects of many parameters such as polymer
concentration, nozzle collector distance, applied voltage, and outer solution
flow rate on creation of the core-shell structure were examined. The morphology
and structure of fibers were characterized using scanning, transmission electron
microscopy, and fourier transform infrared spectroscopy and then retinal
differentiation was examined by quantitative real time PCR (qPCR). Significant
variations between 25% and 35% PEG concentration groups for fiber diameter were
documented. As faster flowing rates from the outer nozzle (PCL fluid) were
applied, the creation possibility of fibrous scaffold was increased. The lowest
diameter and the best quality alignment of core-shell fibrous scaffold were
achieved in 22 Kv and 24 Kv. As rising distancing were applied, the fibrous
diameter increased and spraying was observed. qPCR analysis demonstrated the
differentiation of CJMSCs to photoreceptor like cells on PEG/PCL scaffolds.
According to the result, we have proved successful in the creation of core/shell
fibrous scaffold of PEG/PCL by coaxial electrospinning for retinal tissue
engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A:
189-197, 2017.
PMID- 27615414
TI - The mediating effect of sleep satisfaction on the relationship between stress and
perceived health of adolescents suffering atopic disease: Secondary analysis of
data from the 2013 9th Korea Youth Risk Behavior Web-based Survey.
AB - BACKGROUND: Difficulty in sleep is one disturbing symptom in adolescents with
atopic diseases including asthma, allergic rhinitis, and atopic dermatitis.
Assuming psychological stress can affect adolescents' health status, impaired
sleep quality can be one mediator that negatively impacts the health status of
adolescents with atopic disease. OBJECTIVES: This study aimed to identify the
mediating effect of sleep satisfaction on the relationship between stress and
perceived health status in Korean adolescents with atopic disease and to examine
the differences among three types of atopic disease. DESIGN: A cross-sectional
descriptive study was completed based on secondary analysis of raw data from the
2013 9th Korea Youth Risk Behavior Web-based Survey. SETTINGS AND PARTICIPANTS:
The 21,154 adolescents (29.2%) ever diagnosed and treated for at least one atopic
disease regardless of the symptom presence in a recent year were extracted out of
72,435 survey participants. Then, the 13,216 individuals with exclusively single
atopic diseases were included in analyzing the mediation model. METHODS:
Variables including demographics, stress, perceived health status, and sleep
satisfaction were included. Pearson correlation, one-way ANOVA, path analysis to
define direct/indirect effects with bootstrapping analysis, and multi-group
variance analysis were conducted. RESULTS: High levels of stress in adolescents
with atopic diseases had a significant and direct effect on their negative health
status perception for all atopic disease groups. A significant negative mediating
effect of sleep satisfaction was identified on the relationship between stress
and perceived health status, irrespective of the type of atopic disease. Total
effect and remaining direct effect on the path from stress and perceived health
status via sleep satisfaction was high in adolescents with atopic dermatitis and
allergic rhinitis compared to those with asthma. CONCLUSIONS: To improve sleep
satisfaction for adolescents with atopic diseases, interventions are needed to
enhance the adolescents' perceived health status through stress reduction and
sleep quality improvement.
PMID- 27615415
TI - Continuing professional education: Motivations and experiences of health and
social care professional's part-time study in higher education. A qualitative
literature review.
AB - OBJECTIVES: To understand the motivations and experiences of health and social
care professionals undertaking part-time, accredited, continuing professional
education in higher education. DESIGN: A review following systematic principles.
DATA SOURCES: Systematic searches for literature published between January 2000
and December 2015 using the databases: SCOPUS, Web of Science, Medline,
PsychINFO, Social Policy and Practice and CINAHL. REVIEW METHODS: Studies were
included if they were published in the English language and were qualitative in
design, focussing on the motivations and experiences of staff engaged in part
time, accredited, higher education study. Three reviewers appraised the quality
of the selected studies. RESULTS: Thirteen qualitative studies were identified
for the review. Motivating factors for staff to engage in part-time, accredited,
continuing professional development study included: personal and professional
drivers, influence of workplace/management and funding and availability. Key
themes in relation to how staff experienced study included: the demands of
adjusting to the academic requirements of higher education study; the experience
of juggling competing demands of study, work and family; and the presence or
absence of support for part-time study in the personal and professional arenas.
CONCLUSIONS: Health and social care professionals experience a number of
challenges when engaging in part-time, continuing professional education in
higher education institutions. A significant challenge is the juggling of
competing demands of study, work and family, and this may have a negative impact
on learning. Research is needed to inform how higher education can address the
specific learning needs of this population and develop pedagogic approaches that
are both responsive to need and support of effective learning.
PMID- 27615416
TI - High-temperature operation of broadband bidirectional terahertz quantum-cascade
lasers.
AB - Terahertz quantum cascade lasers (QCLs) with a broadband gain medium could play
an important role for sensing and spectroscopy since then distributed-feedback
schemes could be utilized to produce laser arrays on a single semiconductor chip
with wide spectral coverage. QCLs can be designed to emit at two different
frequencies when biased with opposing electrical polarities. Here, terahertz QCLs
with bidirectional operation are developed to achieve broadband lasing from the
same semiconductor chip. A three-well design scheme with shallow-well
GaAs/Al0.10Ga0.90As superlattices is developed to achieve high-temperature
operation for bidirectional QCLs. It is shown that shallow-well heterostructures
lead to optimal quantum-transport in the superlattice for bidirectional operation
compared to the prevalent GaAs/Al0.15Ga0.85As material system. Broadband lasing
in the frequency range of 3.1-3.7 THz is demonstrated for one QCL design, which
achieves maximum operating temperatures of 147 K and 128 K respectively in
opposing polarities. Dual-color lasing with large frequency separation is
demonstrated for a second QCL, that emits at ~3.7 THz and operates up to 121 K in
one polarity, and at ~2.7 THz up to 105 K in the opposing polarity. These are the
highest operating temperatures achieved for broadband terahertz QCLs at the
respective emission frequencies, and could lead to commercial development of
broadband terahertz laser arrays.
PMID- 27615417
TI - A SPR biosensor based on signal amplification using antibody-QD conjugates for
quantitative determination of multiple tumor markers.
AB - The detection of tumor markers is very important in early cancer diagnosis;
however, tumor markers are usually present at very low concentrations, especially
in the early stages of tumor development. Surface plasmon resonance (SPR) is
widely used to detect biomolecular interactions; it has inherent advantages of
being high-throughput, real-time, and label-free technique. However, its
sensitivity needs essential improvement for practical applications. In this
study, we developed a signal amplification strategy using antibody-quantum dot
(QD) conjugates for the sensitive and quantitative detection of alpha-fetoprotein
(AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1)
in clinical samples. The use of a dual signal amplification strategy using AuNP
antibody and antibody-QD conjugates increased the signal amplification by 50
folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL
for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR
biosensor were consistent with those obtained using the electrochemiluminescence
method. Thus, the constructed SPR biosensor provides a highly sensitive and
specific approach for the detection of tumor markers. This SPR biosensor can be
expected to be readily applied for the detection of other tumor markers and can
offer a potentially powerful solution for tumor screening.
PMID- 27615418
TI - Medication-overuse headache: risk factors, pathophysiology and management.
AB - Medication-overuse headache (MOH) is defined by the International Classification
of Headache Disorders as a headache in patients with a pre-existing primary
headache disorder that occurs on >=15 days per month for >3 months, and is caused
by overuse of medication intended for acute or symptomatic headache treatment.
The prevalence of MOH in the general population is around 1%, but the condition
is much more common in people with headache, in particular chronic migraine. The
phenotype of the headache in MOH depends on the initial primary headache and the
type of overused acute medication. In this Review, we will discuss the
epidemiology, risk factors, pathophysiology, prevention and treatment of MOH.
Treatment of MOH is performed in three steps: educating patients about the
relationship between frequent intake of acute headache medication and MOH with
the aim to reduce intake of acute medication; initiation of migraine prevention
(such as topiramate or onabotulinumtoxin A in migraine) in patients who fail step
1; detoxification on an outpatient basis or in a day hospital or inpatient
setting, depending on severity and comorbidities. The success rate of treatment
is around 50-70%, although patients whose MOH is associated with opioid overuse
have higher relapse rates. In all patients with MOH, relapse rates can be reduced
by patient education and care in the follow-up period.
PMID- 27615421
TI - Multiple sclerosis: Biomarkers and genetic variants reflect disease course in
multiple sclerosis.
PMID- 27615419
TI - Angelman syndrome - insights into a rare neurogenetic disorder.
AB - Angelman syndrome is a rare neurogenetic disorder that is characterized by
microcephaly, severe intellectual deficit, speech impairment, epilepsy, EEG
abnormalities, ataxic movements, tongue protrusion, paroxysms of laughter,
abnormal sleep patterns, and hyperactivity. Angelman syndrome results from loss
of function of the imprinted UBE3A (ubiquitin-protein ligase E3A) gene on
chromosome 15q11.2-q13. This loss of function can be caused by a mutation on the
maternal allele, a 5-7 Mb deletion of the maternally inherited chromosomal
region, paternal uniparental disomy of chromosome 15, or an imprinting defect.
The chromosomal deletion tends to cause the most severe symptoms, possibly owing
to co-deletion of GABA receptor genes. UBE3A mutations and imprinting defects can
be associated with a high risk of recurrence within families. Disruption of UBE3A
function in neurons seems to inhibit synapse formation and experience-dependent
synapse remodelling. Clinical diagnosis of Angelman syndrome in infants and young
children is sometimes difficult, but can be verified by genetic tests. At
present, treatment of symptoms such as seizures is the only medical strategy, but
genetic therapies aimed at activating the silent copy of UBE3A on the paternal
allele are conceivable.
PMID- 27615420
TI - Social networks and neurological illness.
AB - Every patient is embedded in a social network of interpersonal connections that
influence health outcomes. Neurologists routinely need to engage with a patient's
family and friends due to the nature of the illness and its social sequelae.
Social isolation is a potent determinant of poor health and neurobiological
changes, and its effects can be comparable to those of traditional risk factors.
It would seem reasonable, therefore, to map and follow the personal networks of
neurology patients. This approach reveals influential people, their habits, and
linkage patterns that could facilitate or limit health behaviours. Personal
network information can be particularly valuable to enhance risk factor
management, medication adherence, and functional recovery. Here, we propose an
agenda for research and clinical practice that includes mapping the networks of
patients with diverse neurological disorders, evaluating the impact of the
networks on patient outcomes, and testing network interventions.
PMID- 27615423
TI - Correction: A dietary supplement for SUDEP prevention?
PMID- 27615424
TI - Headache: Cluster headache treatment - RCTs versus real-world evidence.
PMID- 27615422
TI - Inflammatory risk factors, biomarkers and associated therapy in ischaemic stroke.
AB - Proinflammatory conditions, including acute and chronic infections, have been
associated with an increased risk of stroke. The risk of stroke is increased by
both the acute and chronic phases of a wide spectrum of proinflammatory
conditions, suggesting that the association is related to activation of the
inflammatory response rather than the condition itself. Different inflammatory
mechanisms probably influence the risk of different stroke subtypes. This
hypothesis is supported by observations that high levels of various immune system
markers and acute phase reactants in otherwise healthy individuals have also been
associated with ischaemic stroke subtypes. C-reactive protein, IL-6 and
lipoprotein-associated phospholipase A2 are some of the inflammatory markers that
have been associated with stroke risk and prognosis. Multiple epidemiological
studies have demonstrated that these markers are associated with the risk of
stroke, but the value of these markers in a clinical setting has not yet been
proven. Further research is needed to determine whether immune system modulators
can lower the risk of stroke in individuals with elevated concentrations of
inflammatory markers. Here, we review the association between infection, systemic
inflammation, and ischaemic stroke, and discuss the currently recommended
preventive methods to decrease the risk of stroke associated with systemic
inflammation.
PMID- 27615425
TI - Biomechanical analysis of immediately loaded implants according to the "All-on
Four" concept.
AB - PURPOSE: The purpose of this study was to investigate the biomechanical behavior
of immediately loaded implants in an edentulous mandible according to the "All-on
Four" concept. METHODS: A 3D-finite element model of an edentulous mandible was
constructed. Four implants were placed between the bilateral mental foramen
according to "All-on-Four" concept. A framework made of titanium or acrylic resin
between the bilateral first molars was modeled. Immediate loading and a delayed
loading protocol were simulated. A vertical load of 200N was applied at the
cantilever or on the abutments region of the distal implants, simulating the
absence of a cantilever. RESULTS: The peak principal compressive strains in the
immediate loading models resulted in 24.0-35.8% and 26.4-39.0% increases compared
with the delayed loading models under non-cantilever loading and cantilever
loading, respectively. The loading position greatly affected the principal
compressive and tensile strain values. The peak principal compressive strains in
non-cantilever loading resulted in a 45.3-52.6% reduction compared with those in
cantilever loading. The framework material did not influence the peak compressive
and tensile strain. The maximum micromotion at the bone-implant interface in the
immediate loading models was 7.5-14.4MUm. CONCLUSIONS: Mandibular fixed full-arch
prostheses without cantilevers may result in a favorable reduction of the peri
implant bone strain during the healing period, compared with cantilevers. The
maximum micromotion was within the acceptable limits for uneventful implant
osseointegration in the immediate loading models. Framework material did not play
an important role in reducing the peri-implant bone strain and micromotion at the
bone-implant interface.
PMID- 27615426
TI - Mouse lysine catabolism to aminoadipate occurs primarily through the saccharopine
pathway; implications for pyridoxine dependent epilepsy (PDE).
AB - Lysine is catabolized in mammals through the saccharopine and pipecolate pathways
- the former is mainly hepatic and renal, and the latter is believed to play a
role in the cerebral lysine oxidation. Both pathways lead to the formation of
aminoadipic semialdehyde (AASA) that is then oxidized to aminoadipate (AAA) by
antiquitin (ALDH7A1). Mutations in the ALDH7A1 gene result in the accumulation of
AASA and its cyclic form, piperideine-6-carboxylate (P6C), which causes
pyridoxine-dependent epilepsy (PDE). P6C reacts with pyridoxal 5'-phosphate (PLP)
causing its inactivation. Here, we used liquid chromatography-mass spectrometry
to investigate lysine catabolism in mice injected with lysine labelled at either
its nitrogen epsilon (epsilon-15N) or nitrogen alpha (alpha-15N). Analysis of
epsilon-15N and alpha-15N lysine catabolites in plasma, liver and brain suggested
the saccharopine as the main pathway for AAA biosynthesis. Although there was
evidence for upstream cerebral pipecolate pathway activity, the resulting
pipecolate does not appear to be further oxidized into AASA/P6C/AAA. By far the
bulk of lysine degradation and therefore, the primary source of lysine
catabolites are hepatic and renal. The results indicate that the saccharopine
pathway is primarily responsible for body's production of AASA/P6C. The
centrality of the saccharopine pathway in whole body lysine catabolism opens new
possibilities of therapeutic targets for PDE. We suggest that inhibition of this
pathway upstream of AASA/P6C synthesis may be used to prevent its accumulation
benefiting PDE patients. Inhibition of the enzyme aminoadipic semialdehyde
synthase, for example, could constitute a new strategy to treat PDE and other
inherited diseases of lysine catabolism.
PMID- 27615427
TI - Post-translational modifications of CD36 (SR-B2): Implications for regulation of
myocellular fatty acid uptake.
AB - The membrane-associated protein CD36, now officially designated as SR-B2, is
present in various tissues and fulfills multiple cellular functions. In heart and
muscle, CD36 is the main (long-chain) fatty acid transporter, regulating
myocellular fatty acid uptake via its vesicle-mediated reversible trafficking
(recycling) between intracellular membrane compartments and the cell surface.
CD36 is subject to various types of post-translational modification. This review
focusses on the role of these modifications in further regulation of myocellular
fatty acid uptake. Glycosylation, ubiquitination and palmitoylation are involved
in regulating CD36 stability, while phosphorylation at extracellular sites affect
the rate of fatty acid uptake. In addition, CD36 modification by O-linked N
acetylglucosamine may regulate the translocation of CD36 from endosomes to the
cell surface. Acetylation of CD36 has also been reported, but possible effects on
CD36 expression and/or functioning have not yet been addressed. Taken together,
CD36 is subject to a multitude of post-translational modifications of which their
functional implications are beginning to be understood. Moreover, further
investigations are needed to disclose whether these post-translational
modifications play a role in altered fatty acid uptake rates seen in several
pathologies of heart and muscle. This article is part of a special issue
entitled: The role of post-translational protein modifications on heart and
vascular metabolism edited by Jason R.B. Dyck and Jan F.C. Glatz.
PMID- 27615428
TI - WITHDRAWN: Emodin increases expression of insulin-like growth factor binding
protein 1 through activation of MEK/ERK/AMPKalpha and interaction of PPARgamma
and Sp1 in lung cancer.
AB - Due to an error in the publishing process, this article has been withdrawn at the
request of the editors. We wish to clarify that this is in no way related to the
integrity of the authors. The Publisher apologizes for any inconvenience this may
cause. The full Elsevier Policy on Article Withdrawal can be found at
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 27615429
TI - A novel ethanol gas sensor based on TiO2/Ag0.35V2O5 branched
nanoheterostructures.
AB - Much greater surface-to-volume ratio of hierarchical nanostructures renders them
attract considerable interest as prototypical gas sensors. In this work, a novel
resistive gas sensor based on TiO2/Ag0.35V2O5 branched nanoheterostructures is
fabricated by a facile one-step synthetic process and the ethanol sensing
performance of this device is characterized systematically, which shows faster
response/recovery behavior, better selectivity, and higher sensitivity of about 9
times as compared to the pure TiO2 nanofibers. The enhanced sensitivity of the
TiO2/Ag0.35V2O5 branched nanoheterostructures should be attributed to the
extraordinary branched hierarchical structures and TiO2/Ag0.35V2O5
heterojunctions, which can eventually result in an obvious change of resistance
upon ethanol exposure. This study not only indicates the gas sensing mechanism
for performance enhancement of branched nanoheterostructures, but also proposes a
rational approach to design nanostructure based chemical sensors with desirable
performance.
PMID- 27615430
TI - The Activity of Fungichromin against the Formation of Candida albicans Biofilm.
AB - The effect of fungichromin (FC) on the formation of Candida albicans biofilm was
assessed using 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5
carboxanilide (XTT) reduction method, scanning electron microscopy (SEM) and
confocal laser scanning microscopy (CLSM). Results showed that FC revealed an
inhibitory effect on the formation of C. albicans biofilm in a dose-dependent
manner with a minimum inhibitory concentration (MIC) of 10 ug/mL. Over 80% of
biofilm formation was inhibited by FC at the concentration of 40 ug/mL when
compared with the control. Similarly, real-time PCR showed that the expression of
the genes such as ALS1, ALS3, HWP1, EFG1, HYR1, CPH1 and BCR1 appeared to be
remarkably affected by FC at the concentration of 20 ug/mL during the biofilm
formation. In addition, FC could also induce the apoptosis of C. albicans cells
in a dose-dependent manner. Therefore, FC displayed potent activity against the
formation of C. albicans biofilm in vitro and played an important role in
reducing the incidence of device-associated infections.
PMID- 27615431
TI - 7-(4-Hydroxyphenyl)-1-phenyl-4E-hepten-3-one, a Diarylheptanoid from Alpinia
officinarum, Protects Neurons against Amyloid-beta Induced Toxicity.
AB - Amyloid-beta (Abeta) is one of the major causative agents of Alzheimer's disease
(AD), the most common neurodegenerative disorder characterized by progressive
cognitive impairment. While effective drugs for AD are currently limited,
identifying anti-Abeta compounds from natural products has been shown as a
promising strategy which may lead to breakthroughs for new drug candidate
discovery. We have previously reported that 7-(4-hydroxyphenyl)-1-phenyl-4E
hepten-3-one (AO-1), a diarylheptanoid extracted from the plant Alpinia
officinarum, has strong effects on neuronal differentiation and neurite outgrowth
in vitro and in vivo. The present study further uncovers that AO-1 exerts
neuroprotective effects against the neurotoxicity caused by Abeta. Under the
damage of Abeta oligomers, the major pathological forms of Abeta, dendrites of
neurons become atrophic and simplified, but such impairments were substantially
alleviated by AO-1 treatment. Moreover, AO-1 reduced apoptotic levels and
oxidative stress triggered by Abeta. Further analysis showed that the anti
caspase and dendrite protective effects of AO-1 were dependent on activation of
phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR)
pathways. These findings collectively identify AO-1 as a beneficial compound to
ameliorate the deleterious effects of Abeta on dendrite integrity and cell
survival, and may provide new insights on drug discovery of AD.
PMID- 27615432
TI - Memory consolidation in children with specific language impairment: Delayed gains
and susceptibility to interference in implicit sequence learning.
AB - In this study, the time course of the procedural learning of a visuomotor
sequence skill was followed over a 24-hour and a 1-week time period in children
with and without specific language impairment (SLI). Two aspects of memory
consolidation in implicit sequence learning were examined: the evolution of post
training gains in sequence knowledge (Experiment 1) and the susceptibility to
interference (Experiment 2). In the first experiment, 18 children with SLI and 17
control children matched for sex, age, and nonverbal intelligence completed a
serial reaction-time (SRT) task and were tested 24 hours and 1 week after
practicing. The two groups of children attained an equal level of sequence
knowledge in the training session, but the children with SLI lacked the
consolidation gains displayed by the control children in the two post-training
sessions. Working with a new group of children, 17 with SLI and 17 control peers,
Experiment 2 examined resistance to interference by introducing a second sequence
15 min after the first training session. Similar results were obtained for the
performance of both groups in the training session. However, although the
performance of the control group improved in the post-training sessions, the
performance of the SLI group deteriorated significantly during the consolidation
phase due to the interfering sequence. These findings suggest that the
consolidation phase of sequence learning is impaired in children with SLI.
PMID- 27615433
TI - Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse
ventral tegmental area that project to nucleus accumbens and other mesolimbic
targets.
AB - The mesolimbic dopamine (DA) circuitry determines which behaviors are positively
reinforcing and therefore should be encoded in the memory to become a part of the
behavioral repertoire. Natural reinforcers, like food and sex, activate this
pathway, thereby increasing the likelihood of further consummatory, social, and
sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward
and OT-synthesizing neurons project to the ventral tegmental area (VTA) and
nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT
regulation of DA neurons within the VTA is sparse. To phenotype OT-receptor (OTR)
expressing neurons originating within the VTA, we delivered Cre-inducible adeno
associated virus that drives the expression of fluorescent marker into the VTA of
male mice that had Cre-recombinase driven by OTR gene expression. OTR-expressing
VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other
forebrain regions but less than 10% of these OTR-expressing neurons were
identified as DA neurons (defined by tyrosine hydroxylase colocalization).
Instead, almost 50% of OTR-expressing cells in the VTA were glutamate (GLU)
neurons, as indicated by expression of mRNA for the vesicular GLU transporter
(vGluT). About one-third of OTR-expressing VTA neurons did not colocalize with
either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons
implicates that OT regulation of reward circuitry is more complex than a direct
action on DA neurotransmission. J. Comp. Neurol. 525:1094-1108, 2017. (c) 2016
Wiley Periodicals, Inc.
PMID- 27615434
TI - Surface-Induced Protein Unfolding in Submicron Electrospray Emitters.
AB - The charging of protein ions formed by nanoelectrospray ionization (nanoESI) with
tips that are between 1.5 MUm and 250 nm in outer diameter is compared. More
charging is obtained with the smaller tip sizes for proteins that have a net
positive charge in solution, and additional high-charge-state distributions are
often observed. A single charge-state distribution of holo-myoglobin ions is
produced by nanoESI from a slightly acidified aqueous solution with the micron
outer diameter tips, but some apo-myoglobin ions are produced with the submicron
tips. In contrast, the charge-state distributions for proteins with a net
negative charge in solution do not depend on tip size. Both the formation of high
charge states and the appearance of higher-charge-state distributions, as well as
the loss of the heme group from myoglobin, indicate that a fraction of the
protein population is unfolding with the smaller tips. The increased charging
with the smaller tip sizes for proteins with a net positive charge but not for
proteins with a net negative charge indicates that the unfolding occurs prior to
nanoelectrospray ionization as a result of Coulombic attraction between
positively charged protein molecules in solution and the glass surfaces of the
emitter tips that are negatively charged. These results demonstrate a novel
method for producing highly charged protein ions that does not require exposing
the proteins to additional chemicals either in solution or in the gas phase.
PMID- 27615435
TI - Robotic Assisted Simple Prostatectomy versus Holmium Laser Enucleation of the
Prostate for Lower Urinary Tract Symptoms in Patients with Large Volume Prostate:
A Comparative Analysis from a High Volume Center.
AB - PURPOSE: We report a comparative analysis of robotic assisted simple
prostatectomy vs holmium laser enucleation of the prostate in patients who had
benign prostatic hyperplasia with a large volume prostate (greater than 100 ml).
MATERIALS AND METHODS: A total of 81 patients underwent robotic assisted simple
prostatectomy and 45 underwent holmium laser enucleation of the prostate in a 7
year period. Patients were preoperatively assessed with transrectal ultrasound
and uroflowmetry. Functional parameters were assessed postoperatively during
followup. Perioperative outcomes included operative time, postoperative
hemoglobin, catheterization time and hospitalization. Complications were reported
according to the Clavien-Dindo classification. RESULTS: Compared to the holmium
laser enucleation group, patients treated with prostatectomy were significantly
younger (median age 69 vs 74 years, p = 0.032) and less healthy (Charlson
comorbidity index 2 or greater in 62% vs 29%, p = 0.0003), and had a lower rate
of suprapubic catheterization (23% vs 42%, p = 0.028) and a higher preoperative I
PSS (International Prostate Symptom Score) (25 vs 21, p = 0.049). Both groups
showed an improvement in the maximum flow rate (15 vs 11 ml per second, p = 0.7),
and a significant reduction in post-void residual urine (-73 vs -100 ml, p = 0.4)
and I-PSS (-20 vs -18, p = 0.8). Median operative time (105 vs 105 minutes, p =
0.9) and postoperative hemoglobin (13.2 vs 13.8 gm/dl, p = 0.08) were similar for
robotic assisted prostatectomy and holmium laser enucleation, respectively.
Median catheterization time (3 vs 2 days, p = 0.005) and median hospitalization
(4 vs 2 days, p = 0.0001) were slightly shorter in the holmium laser group.
Complication rates were similar with no Clavien grade greater than 3 in either
group. CONCLUSIONS: Our results from a single center suggest comparable outcomes
for robotic assisted simple prostatectomy and holmium laser enucleation of the
prostate in patients with a large volume prostate. These findings require
external validation at other high volume centers.
PMID- 27615436
TI - Comparison of Silodosin and Naftopidil for Efficacy in the Treatment of Benign
Prostatic Enlargement Complicated by Overactive Bladder: A Randomized,
Prospective Study (SNIPER Study).
AB - PURPOSE: We investigated the efficacy of 2 alpha1-blockers with different
affinities for the alpha1-adrenoceptor subtypes silodosin and naftopidil in the
treatment of benign prostatic enlargement complicated by overactive bladder.
MATERIALS AND METHODS: This was a prospective, open label, randomized,
multicenter study of 350 outpatients with untreated benign prostatic enlargement
associated with urinary urgency at least once per week and an OABSS (Overactive
Bladder Symptom Score) of 3 or greater. Patients were randomly assigned to
receive silodosin 8 mg per day or naftopidil 75 mg per day. Changes in parameters
from baseline to 4 and 12 weeks were assessed based on I-PSS (International
Prostate Symptom Score), I-PSS quality of life, OABSS and voiding functions
measured by uroflowmetry. RESULTS: On efficacy analysis a total of 314 patients
were included in the 2 groups. No significant difference in adverse effects was
observed between the groups. Mean I-PSS and I-PSS quality of life scores, and
OABSS significantly improved in both groups. Statistically significantly greater
improvement in the silodosin group than in the naftopidil group was observed in
total OABSS (p = 0.03), I-PSS quality of life score (p = 0.005) and OABSS urgency
score (p <0.001) at 12 weeks. In regard to voiding function the maximum urinary
flow rate showed significant improvements in both groups but the change in the
maximum flow rate in the silodosin group at 12 weeks was significantly greater
than in the naftopidil group (3.6 vs 2.1 ml per second). CONCLUSIONS: Silodosin,
a pure alpha1A-adrenoceptor blocker, showed greater improvement in overactive
bladder symptoms along with the urinary flow rate in patients with benign
prostatic enlargement complicated by overactive bladder compared to naftopidil,
an alpha1D>A-adrenoceptor blocker.
PMID- 27615437
TI - HoBi-Like Virus RNA Detected in Foetuses Following Challenge of Pregnant Cows
that had Previously Given Birth to Calves Persistently Infected with Bovine Viral
Diarrhoea Virus.
AB - The ability of ruminant pestivirus including bovine viral diarrhoea virus (BVDV)
and the related emerging pestivirus, HoBi-like virus, to establish persistent
infection (PI) following foetal infection is central to keeping these viruses in
circulation. Non-PI dams carrying BVDV PI calves develop high levels of immunity
due constantly viral exposure. A study to determine whether the immunity
developed following the generation of a BVDV PI is enough to prevent HoBi-like
virus infection of a subsequent foetus was performed. This study consisted of
nine pregnant cows, four had birthed BVDV-1 PI calves in a previous pregnancy,
three cows had birthed BVDV-2 PIs and two had birthed pestivirus negative calves.
From this, six pregnant cows were challenged with HoBi-like virus about day 85 of
gestation (four BVDV-1 and two BVDV-2 cows) and three non-challenged cows
(negative control). At the day of challenge, the serum neutralizing titres
against the homologous BVDV strains of the first inoculation ranged from 1148 to
5793. At day 6 post-challenge, HoBi-like RNA was detected in the serum of all
four BVDV-1 cows but not in the two BVDV-2 cows. The foetuses harvested from five
of the exposed dams (three BVDV-1 and two BVDV-2 cows) at day 30 post-challenge
were positive for HoBi-like virus RNA. The sixth cow, BVDV-1 cow #541, while
pregnant at the time of exposure, had no foetus 30 days after exposure. Foetuses
from HoBi-like virus exposed dams were significantly smaller and lighter than
control foetuses. HoBi-like RNA was detected in samples of all challenged
foetuses. The identification of viral RNA in the serum of 4 cows at day 6 post
challenge, as well viral RNA detection in all foetuses 30 days post-inoculation,
indicates that the foetuses of dams with high antibodies titres against BVDV-1 or
BVDV-2 would not be protected from challenge with a HoBi-like virus.
PMID- 27615438
TI - Where the Buffalo Have Evolutionarily Roamed.
PMID- 27615439
TI - Intraoperative cervix location and apical support stiffness in women with and
without pelvic organ prolapse.
AB - BACKGROUND: It is unknown how initial cervix location and cervical support
resistance to traction, which we term "apical support stiffness," compare in
women with different patterns of pelvic organ support. Defining a normal range of
apical support stiffness is important to better understand the pathophysiology of
apical support loss. OBJECTIVE: The aims of our study were to determine whether:
(1) women with normal apical support on clinic Pelvic Organ Prolapse
Quantification, but with vaginal wall prolapse (cystocele and/or rectocele), have
the same intraoperative cervix location and apical support stiffness as women
with normal pelvic support; and (2) all women with apical prolapse have abnormal
intraoperative cervix location and apical support stiffness. A third objective
was to identify clinical and biomechanical factors independently associated with
clinic Pelvic Organ Prolapse Quantification point C. STUDY DESIGN: We conducted
an observational study of women with a full spectrum of pelvic organ support
scheduled to undergo gynecologic surgery. All women underwent a preoperative
clinic examination, including Pelvic Organ Prolapse Quantification. Cervix
starting location and the resistance (stiffness) of its supports to being moved
steadily in the direction of a traction force that increased from 0-18 N was
measured intraoperatively using a computer-controlled servoactuator device. Women
were divided into 3 groups for analysis according to their pelvic support as
classified using the clinic Pelvic Organ Prolapse Quantification: (1)
"normal/normal" was women with normal apical (C < -5 cm) and vaginal (Ba and Bp <
0 cm) support; (2) normal/prolapse had normal apical support (C < -5 cm) but
prolapse of the anterior or posterior vaginal walls (Ba and/or Bp >= 0 cm); and
(3) prolapse/prolapse had both apical and vaginal wall prolapse (C > -5 cm and Ba
and/or Bp >= 0 cm). Demographics, intraoperative cervix locations, and apical
support stiffness values were then compared. Normal range of cervix location
during clinic examination and operative testing was defined by the total range of
values observed in the normal/normal group. The proportion of women in each group
with cervix locations within and outside the normal range was determined. Linear
regression was performed to identify variables independently associated with
clinic Pelvic Organ Prolapse Quantification point C. RESULTS: In all, 52 women
were included: 14 in the normal/normal group, 11 in the normal/prolapse group,
and 27 in the prolapse/prolapse group. At 1 N of traction force in the operating
room, 50% of women in the normal/prolapse group had cervix locations outside the
normal range while 10% had apical support stiffness outside the normal range. Of
women in the prolapse/prolapse group, 81% had cervix locations outside the normal
range and 8% had apical support stiffness outside the normal range. Similar
results for cervix locations were observed at 18 N of traction force; however the
proportion of women with apical support stiffness outside the normal range
increased to 50% in the normal/prolapse group and 59% in the prolapse/prolapse
group. The prolapse/prolapse group had statistically lower apical support
stiffness compared to the normal/normal group with increased traction from 1-18 N
(0.47 +/- 0.18 N/mm vs 0.63 +/- 0.20 N/mm, P = .006), but all other comparisons
were nonsignificant. After controlling for age, parity, body mass index, and
apical support stiffness, cervix location at 1 N traction force remained an
independent predictor of clinic Pelvic Organ Prolapse Quantification point C, but
only in the prolapse/prolapse group. CONCLUSION: Approximately 50% of women with
cystocele and/or rectocele but normal apical support in the clinic had cervix
locations outside the normal range under intraoperative traction, while 19% of
women with uterine prolapse had normal apical support. Identifying women whose
apical support falls outside a defined normal range may be a more accurate way to
identify those who truly need a hysterectomy and/or an apical support procedure
and to spare those who do not.
PMID- 27615440
TI - Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1).
AB - BACKGROUND: Uterine inflammatory processes trigger prolabor pathways and
orchestrate on-time labor onset. Although essential for successful labor,
inflammation needs to be regulated to avoid uncontrolled amplification and
resolve postpartum. During labor, myometrial smooth muscle cells generate ATP
mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from
its metabolic function, lactate has been shown to activate a G protein-coupled
receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that
lactate produced during labor may act via GPR81 in the uterus to exert in a
feedback manner antiinflammatory effects, to resolve or mitigate inflammation.
OBJECTIVE: We sought to investigate the role of lactate produced during labor and
its receptor, GPR81, in regulating inflammation in the uterus. STUDY DESIGN: We
investigated the expression of GPR81 in the uterus and the pharmacological role
of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81-/- mice.
RESULTS: (1) Uterine lactate levels increased substantially from 2 to 9 mmol/L
during labor. (2) Immunohistological analysis revealed expression of GPR81 in the
uterus with high expression in myometrium. (3) GPR81 expression increased during
gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell
and ex vivo uteri from wild-type mice, lactate decreased interleukin-1beta
induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2;
suppressive effects of lactate were not observed in cells and tissues from GPR81
/- mice. (5) Conversely, proinflammatory gene expression was augmented in the
uterus at term in GPR81-/- mice and wild-type mice treated intrauterine with
lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene
transcription in the uterus when labor was induced by endotoxin
(lipopolysaccharide). (6) Importantly, administration to pregnant mice of a
metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased
endotoxin-induced uterine inflammation, preterm birth, and associated neonatal
mortality. CONCLUSION: Collectively, our data uncover a novel link between the
anaerobic glycolysis and the control of uterine inflammation wherein the high
levels of lactate produced during labor act on uterine GPR81 to down-regulate key
proinflammatory genes. This discovery may represent a novel feedback mechanism to
regulate inflammation during labor, and conveys a potential rationale for the use
of GPR81 agonists to attenuate inflammation and resulting preterm birth.
PMID- 27615441
TI - Extracellular matrix regenerative graft attenuates the negative impact of
polypropylene prolapse mesh on vagina in rhesus macaque.
AB - BACKGROUND: The use of wide pore lightweight polypropylene mesh to improve
anatomical outcomes in the surgical repair of prolapse has been hampered by mesh
complications. One of the prototype prolapse meshes has been found to negatively
impact the vagina by inducing a decrease in smooth muscle volume and
contractility and the degradation of key structural proteins (collagen and
elastin), resulting in vaginal degeneration. Recently, bioscaffolds derived from
extracellular matrix have been used to mediate tissue regeneration and have been
widely adopted in tissue engineering applications. OBJECTIVE: Here we aimed to:
(1) define whether augmentation of a polypropylene prolapse mesh with an
extracellular matrix regenerative graft in a primate sacrocolpopexy model could
mitigate the degenerative changes; and (2) determine the impact of the
extracellular matrix graft on vagina when implanted alone. STUDY DESIGN: A
polypropylene-extracellular matrix composite graft (n = 9) and a 6-layered
extracellular matrix graft alone (n = 8) were implanted in 17 middle-aged parous
rhesus macaques via sacrocolpopexy and compared to historical data obtained from
sham (n = 12) and the polypropylene mesh (n = 12) implanted by the same method.
Vaginal function was measured in passive (ball-burst test) and active (smooth
muscle contractility) mechanical tests. Vaginal histomorphologic/biochemical
assessments included hematoxylin-eosin and trichrome staining, immunofluorescent
labeling of alpha-smooth muscle actin and apoptotic cells, measurement of total
collagen, collagen subtypes (ratio III/I), mature elastin, and sulfated
glycosaminoglycans. Statistical analyses included 1-way analysis of variance,
Kruskal-Wallis, and appropriate post-hoc tests. RESULTS: The host inflammatory
response in the composite mesh-implanted vagina was reduced compared to that
following implantation with the polypropylene mesh alone. The increase in
apoptotic cells observed with the polypropylene mesh was blunted in the composite
(overall P < .001). Passive mechanical testing showed inferior parameters for
both polypropylene mesh alone and the composite compared to sham whereas the
contractility and thickness of smooth muscle layer in the composite were improved
with a value similar to sham, which was distinct from the decreases observed with
polypropylene mesh alone. Biochemically, the composite had similar mature elastin
content, sulfated glycosaminoglycan content, and collagen subtype III/I ratio but
lower total collagen content when compared to sham (P = .011). Multilayered
extracellular matrix graft alone showed overall comparable values to sham in
aspects of the biomechanical, histomorphologic, or biochemical endpoints of the
vagina. The increased collagen subtype ratio III/I with the extracellular matrix
graft alone (P = .033 compared to sham) is consistent with an ongoing active
remodeling response. CONCLUSION: Mesh augmentation with a regenerative
extracellular matrix graft attenuated the negative impact of polypropylene mesh
on the vagina. Application of the extracellular matrix graft alone had no
measurable negative effects suggesting that the benefits of this extracellular
matrix graft occur when used without a permanent material. Future studies will
focus on understanding mechanisms.
PMID- 27615442
TI - A mix of apple pomace polysaccharide improves mitochondrial function and reduces
oxidative stress in the liver of high-fat diet-induced obese mice.
AB - SCOPE: Apple pomace polysaccharides (APP), a free radical scavenger, is one of
the major compounds derived from apple pomace. However, whether APP has
beneficial effects on metabolic disorders is still unknown. METHODS AND RESULTS:
In the present study, water-soluble APP was isolated from the pomace of the
locally abundant "Qinguan" apple and chemically characterized. Then, APP was
orally administrated to high-fat diet (HFD)-induced obese mice. We found that APP
significantly reduced HFD-induced body weight gain and ameliorated HFD-induced
hepatic metabolic disorders and oxidative stress. In a palmitate-loaded HepG2
cell model, APP protected the cells from palmitate-induced insulin resistance and
loss of viability by suppressing mitochondrial reactive oxygen species and
rescuing mitochondrial respiratory function. CONCLUSION: Our work suggests that
APP, a promising bioactive food component, successfully improved obesity
associated hepatic metabolic disorder, most likely though the activation of
hepatic mitochondrial function and the suppression of mitochondria oxidative
stress.
PMID- 27615443
TI - Do different types of bearings and noise from total hip arthroplasty influence
hip-related pain, function, and quality of life postoperatively?
AB - Background and purpose - Patient-reported outcome (PRO) is recognized as an
important tool for evaluating the outcome and satisfaction after total hip
arthroplasty (THA). We wanted to compare patient-reported outcome measure (PROM)
scores from patients with ceramic-on-ceramic (CoC) THAs and those with metal-on
metal (MoM) THAs to scores from patients with metal-on-polyethylene (MoP) THAs,
and to determine the influence of THA-related noise on PROM scores. Patients and
methods - We conducted a nationwide cross-sectional questionnaire survey in a
cohort of patients identified from the Danish Hip Arthroplasty Registry. The
PROMs included were: hip dysfunction and osteoarthritis and outcome score (HOOS),
EQ-5D-3L, EQ VAS, UCLA activity score, and questions about noise from the THA.
The response rate was 85% and the number of responders was 3,089. Of these, 45%
had CoC THAs, 17% had MoM THAs, and 38% had MoP THAs, with a mean length of
follow-up of 7, 5, and 7 years, respectively. Results - Compared to MoP THAs, the
mean PROM scores for CoC and MoM THAs were similar, except that CoC THAs had a
lower mean score for HOOS Symptoms than did MoP THA. 27% of patients with CoC
THAs, 29% with MoM THAs, and 12% with MoP THAs reported noise from their hip. For
the 3 types of bearings, PROM scores from patients with a noisy THA were
statistically significantly worse than those from patients with a silent MoP THA.
The exception was noisy CoC and MoM THAs, which had the same mean UCLA activity
score as silent MoP THAs. Interpretation - A high proportion of patients reported
noise from the THA, and these patients had worse PROM scores than patients with
silent MoP THAs.
PMID- 27615444
TI - Aspirin prevents bone loss with little mechanical improvement in high-fat-fed
ovariectomized rats.
AB - Obesity and osteoporosis are often concurrently happened in the menopausal women.
Obesity in menopausal women is not only related to a high risk of cardiovascular
disease, but also results in a detrimental effect on bone health. This study
aimed to investigate the effects of aspirin, a popular anti-thrombosis drug, on
bone quantity and quality in the high-fat-fed animal model. Adult female rats
were subjected to either sham operations or ovariectomized operations. The
ovariectomized rats were orally administered with deionized water or standardized
high fat emulsion with or without aspirin. All rats were injected with calcein
before killed for the purpose of double in vivo labeling. Biochemistry,
histomorphometry, micro-computed tomography analysis, mechanical test, and
component analysis were performed after 12 weeks. In vitro cell culture was also
performed to observe the effect of aspirin in osteogenesis. We found that high
fat remarkably impaired bone formation and bone biomechanics. Aspirin treatment
significantly prevented bone loss by increasing bone formation. In vitro studies
also validated the enhancement of osteogenic differentiation. However, aspirin
presented no significant improvement in bone mechanical properties. Component
analysis shown aspirin could significantly increase the content of mineral, but
had limited effect on the content of collagen. In conclusion, aspirin is
beneficial for the prevention of bone loss; meanwhile, it may cause an imbalance
in the components of bone which may weaken the mechanical properties. The current
study provided further evidence that aspirin might not be powerful for the
prevention of fracture in osteoporotic patients.
PMID- 27615445
TI - Pharmaceutical evaluation of naftopidil enantiomers: Rat functional assays in
vitro and estrogen/androgen induced rat benign prostatic hyperplasia model in
vivo.
AB - Naftopidil (NAF) is a alpha1D/1A adrenoceptor selective drug used for the
treatment of both benign prostatic hyperplasia and lower urinary tract symptoms
(BPH/LUTS). However, NAF is used as a racemate in clinic. To compare the
differences and similarities among two enantiomers and racemate, pharmacological
activities were evaluated through rat functional assays in vitro and
estrogen/androgen (E/T) induced rat BPH model in vivo. NAF and the two
enantiomers showed similar blocking activity on alpha1 receptor. S-NAF exhibited
more alpha1D/1A adrenoceptor subtype selectivity than R-NAF and the racemate. The
selectivity ratios pA2 (alpha1D)/pA2 (alpha1B) and pA2 (alpha1A)/pA2 (alpha1B)
were 40.7- and 16.2-fold, respectively. NAF and its enantiomers effectively
prevented the development of rat prostatic hyperplasia via suppressing the
increase of the prostatic wet weight, visually. The quantitative analysis of the
relative acinus volume, relative stroma volume, relative epithelial volume,
epithelial height and expression of proliferating cell nuclear antigen (PCNA) and
alpha-smooth muscle actin (alpha-SMA) were carried out. S-NAF showed an advantage
on the effect of inhibiting prostate wet weight and stroma volume over R-NAF and
racemate NAF (P<0.05). Nevertheless, no other significant difference was observed
between these two enantiomers. In conclusion, both R-NAF and S-NAF not only relax
prostate muscle but also inhibit the prostate growth, thus relieve BPH.
PMID- 27615446
TI - The effect of nitrazepam on depression and curiosity in behavioral tests in mice:
The role of potassium channels.
AB - Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in
depression, so the aim of this study was to investigate the effect of nitrazepam
as agonist of GABAA receptors on depression and curiosity in male mice and the
role of potassium channel in antidepressant-like response. For this purpose, we
studied the antidepressant-like properties of fluoxetine, nitrazepam,
glibenclamide, and cromakalim by both forced swimming test (FST) and tail
suspension test (TST). Animals were injected by various doses of nitrazepam
(0.05, 0.1, and 0.5mg/kg). Nitrazepam at dose of 0.5mg/kg significantly decreased
the immobility time compared to control group in both FST and TST. Fluoxetine
also showed such a response. Co-administration of nitrazepam (0.05mg/kg) with
glibenclamide in TST (1mg/kg) and in FST (0.3, 1mg/kg) also showed antidepressant
like response. Beside, cromakalim (0.1mg/kg) could reverse the antidepressant
like effect of nitrazepam (0.5mg/kg) in both FST and TST, while cromakalim and
glibenclamide alone could not change the immobility time compared to control
group (P>0.05). The hole-board test revealed that nitrazepam at doses of 0.5 and
0.1mg/kg could increase the activity of the animal's head-dipping and boost the
curiosity and exploration behavior of mice. The results of this study revealed
that nitrazepam may possess antidepressant-like properties and this effect is
dependent to potassium channels in both FST and TST.
PMID- 27615447
TI - Intermittent hypoxia in obese Zucker rats: cardiometabolic and inflammatory
effects.
AB - NEW FINDINGS: What is the central question of this study? This study addresses
the relative impact of obesity and intermittent hypoxia in the pathophysiological
process of obstructive sleep apnoea by investigating the metabolic, inflammatory
and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker
rats. What is the main finding and its importance? We found that obesity and
intermittent hypoxia have mainly distinct consequences on the investigated
inflammatory and cardiometabolic parameters in Zucker rats. This suggests that,
for a given severity of sleep apnea, the association of obesity and obstructive
sleep apnoea may not necessarily be deleterious. Obstructive sleep apnoea is
associated with obesity with a high prevalence, and both co-morbidities are
independent cardiovascular risk factors. Intermittent hypoxia (IH) is thought to
be the main factor responsible for the obstructive sleep apnoea-related
cardiometabolic alterations. The aim of this study was to assess the respective
impact of obesity and IH on the inflammatory and cardiometabolic state in rats.
Lean and obese Zucker rats were exposed to normoxia or chronic IH, and we
assessed metabolic and inflammatory parameters, such as plasma lipids and
glucose, serum leptin and adiponectin, liver cytokines, nuclear factor-kappaB
activity and cardiac endothelin-1 levels. Myocardial infarct size was also
evaluated following in vitro ischaemia-reperfusion. Circulating lipids, insulin,
homeostasis model assessment of insulin resistance (HOMA-IR), leptin and
adiponectin levels were higher in obese versus lean rats. Chronic IH did not have
a significant impact on metabolic parameters in lean rats. In obese rats, IH
increased glycaemia and HOMA-IR. Liver interleukin-6 and tumour necrosis factor
alpha levels were elevated in lean rats exposed to IH; obesity prevented the
increase in interleukin-6 but not in tumour necrosis factor-alpha. Finally, IH
exposure enhanced myocardial sensitivity to infarction in both lean and obese
rats and increased cardiac endothelin-1 in lean but not obese rats. In
conclusion, this study shows that the dyslipidaemia and insulin resistance
induced by obesity of genetic origin does not enhance the deleterious
cardiovascular response to IH and may even partly protect against IH-induced
inflammation.
PMID- 27615449
TI - Synthesis of Fmoc-Protected Arylphenylalanines (Bip Derivatives) via Nonaqueous
Suzuki-Miyaura Cross-Coupling Reactions.
AB - A one-step synthesis of Fmoc-protected aryl/heteroaryl-substituted phenylalanines
(Bip derivatives) using the nonaqueous palladium-catalyzed Suzuki-Miyaura cross
coupling (SMC) reaction of Fmoc-protected bromo- or iodophenylalanines is
reported. This protocol allows for the direct formation of a variety of unnatural
biaryl-containing amino acids in good to excellent yield, which can be readily
used in subsequent Fmoc solid-phase peptide synthesis. The synthetic utility of
this method is also demonstrated by the SMC reaction of bromophenylalanine
containing tripeptides.
PMID- 27615448
TI - The Volume of the Spleen and Its Correlates after Acute Stroke.
AB - BACKGROUND: Animal studies describe changes in the spleen following a stroke,
with an immediate reduction in volume associated with changes in the counts of
specific blood white blood cell (WBCs). This brain-spleen cell cycling after
stroke affects systemic inflammation and the brain inflammatory milieu and may be
a target for emerging therapeutic studies. This study aimed to evaluate features
of this brain-spleen model in human patients admitted for acute stroke. METHODS:
Medical and imaging records were retrospectively reviewed for 82 consecutive
patients admitted for acute stroke in whom an abdominal computed tomography scan
was performed. RESULTS: Mean +/- SD splenic volume was 224.5 +/- 135.5 cc.
Splenic volume varied according to gender (P = .014) but not stroke subtype
(ischemic versus hemorrhagic, P = .76). The change in splenic volume over time
was biphasic (P = .04), with splenic volumes initially decreasing over time,
reaching a nadir 48 hours after stroke onset, then increasing thereafter. Splenic
volume was related inversely to percent blood lymphocytes (r = -.36, P = .001)
and positively to percent blood neutrophils (r = .30, P = .006). CONCLUSIONS:
Current results support that several features of brain-spleen cell cycling after
stroke described in preclinical studies extend to human subjects, including the
immediate contraction of splenic volume associated with proportionate changes in
blood WBC counts. Splenic volume may be useful as a biomarker of systemic
inflammatory events in clinical trials of interventions targeting the immune
system after stroke.
PMID- 27615450
TI - Learning from evolutionary optimisation: what are toughening mechanisms good for
in dentine, a nonrepairing bone tissue?
AB - The main mass of material found in teeth is dentine, a bone-like tissue, riddled
with micron-sized tubules and devoid of living cells. It provides support to the
outer wear-resistant layer of enamel, and exhibits toughening mechanisms which
contribute to crack resistance. And yet unlike most bone tissues, dentine does
not remodel and consequently any accumulated damage does not 'self repair'.
Because damage containment followed by tissue replacement is a prime reason for
the crack-arresting microstructures found in most bones, the occurrence of
toughening mechanisms without the biological capability to repair is puzzling.
Here we consider the notion that dentine might be overdesigned for strength,
because it has to compensate for the lack of cell-mediated healing mechanisms.
Based on our own and on literature-reported observations, including quasistatic
and fatigue properties, dentine design principles are discussed in light of the
functional conditions under which teeth evolved. We conclude that dentine is only
slightly overdesigned for everyday cyclic loading because usual mastication
stresses may come close to its endurance strength. The in-built toughening
mechanisms constitute an evolutionary benefit because they prevent catastrophic
failure during rare overload events, which was probably very advantageous in our
hunter gatherer ancestor times. From a bio-inspired perspective, understanding
the extent of evolutionary overdesign might be useful for optimising biomimetic
structures used for load bearing.
PMID- 27615451
TI - Freestanding bacterial cellulose-graphene oxide composite membranes with high
mechanical strength for selective ion permeation.
AB - Graphene oxide (GO) based membranes have been widely applied in molecular
separation based on the size exclusion effect of the nanochannels formed by
stacked GO sheets. However, it's still a challenge to prepare a freestanding GO
based membrane with high mechanical strength and structural stability which is
prerequisite for separation application in aqueous solution. Here, a freestanding
composite membrane based on bacterial cellulose (BC) and GO is designed and
prepared. BC network provides a porous skeleton to spread GO sheets and uniformly
incorporates into the GO layers, which endows the BC + GO composite membrane with
well water-stability, excellent tensile strength, as well as improved toughness,
guaranteeing its separation applicability in water environment. The resulting BC
+ GO membrane exhibits obviously discrepant permeation properties for different
inorganic/organic ions with different size, and in particular, it can quickly
separate ions in nano-scale from angstrom-scale. Therefore, this novel composite
membrane is considered to be a promising candidate in the applications of water
purification, food industry, biomedicine, and pharmaceutical and fuel separation.
PMID- 27615452
TI - Decrease in newly generated oligodendrocytes leads to motor dysfunctions and
changed myelin structures that can be rescued by transplanted cells.
AB - NG2-glia in the adult brain are known to proliferate and differentiate into
mature and myelinating oligodendrocytes throughout lifetime. However, the role of
these newly generated oligodendrocytes in the adult brain still remains little
understood. Here we took advantage of the Sox10-iCreERT2 x CAG-eGFP x Esco2fl/fl
mouse line in which we can specifically ablate proliferating NG2-glia in adult
animals. Surprisingly, we observed that the generation of new oligodendrocytes in
the adult brain was severely affected, although the number of NG2-glia remained
stable due to the enhanced proliferation of non-recombined cells. This lack of
oligodendrogenesis led to the elongation of the nodes of Ranvier as well as the
associated paranodes, which could be locally rescued by myelinating
oligodendrocytes differentiated from transplanted NG2-glia deriving from wildtype
mice. Repetitive measurements of conduction velocity in the corpus callosum of
awake animals revealed a progressive deceleration specifically in the mice
lacking adult oligodendrogenesis that resulted in progressive motor deficits. In
summary, here we demonstrated for the first time that axon function is not only
controlled by the reliable organization of myelin, but also requires a dynamic
and continuous generation of new oligodendrocytes in the adult brain. GLIA
2016;64:2201-2218.
PMID- 27615453
TI - A Microfiltration Polymer-Based Hollow-Fiber Cathode as a Promising Advanced
Material for Simultaneous Recovery of Energy and Water.
AB - A novel electrocatalytic and microfiltration polymeric hollow fiber is fabricated
for simultaneous recovery of energy (H2 ) and clean fresh water from wastewater,
hence addressing two grand challenges facing society in the current century
(i.e., providing adequate supplies of clean fresh water and energy as the world's
population increases).
PMID- 27615454
TI - Bioactivity of Phytosterols and Their Production in Plant in Vitro Cultures.
AB - Phytosterols are a kind of plant metabolite belonging to the triterpene family.
These compounds are essential biomolecules for human health, and so they must be
taken from foods. beta-Sitosterol, campesterol, and stigmasterol are the main
phytosterols found in plants. Phytosterols have beneficial effects on human
health since they are able to reduce plasma cholesterol levels and have
antiinflammatory, antidiabetic, and anticancer activities. However, there are
many difficulties in obtaining them, since the levels of these compounds produced
from plant raw materials are low and their chemical synthesis is not economically
profitable for commercial exploitation. A biotechnological alternative for their
production is the use of plant cell and hairy root cultures. This review is
focused on the biosynthesis of phytosterols and their function in both plants and
humans as well as the different biotechnological strategies to increase
phytosterol biosynthesis. Special attention is given to describing new
methodologies based on the use of recombinant DNA technology to increase the
levels of phytosterols.
PMID- 27615503
TI - Adherence to the Women's Preventive Services Guidelines in the Affordable Care
Act.
AB - OBJECTIVE: To assess the adherence of women's health providers in New Mexico to
the Women's Preventive Services Guidelines and to examine how providers'
knowledge, attitudes, and external barriers are associated with adherence.
DESIGN: Cross-sectional, descriptive survey. SETTING: New Mexico. PARTICIPANTS:
Women's health providers in New Mexico, including nurse practitioners, certified
nurse-midwives, and family practice and obstetrician-gynecologist physicians.
METHODS: Participants completed a self-administered survey to measure knowledge,
attitudes, external barriers, and adherence to each of the eight guidelines.
Adherence was defined as following a guideline more than 90% of the time.
RESULTS: The response rate was 22% (399/1,798). Among the eight guidelines,
participant adherence ranged from 17.2% to 88.4%. Only 39.7% of participants
indicated adherence to most of the guidelines (four or more). Overall, provider
adherence was directly associated with familiarity with the guidelines (odds
ratio = 3.69; 95% confidence interval [1.96, 6.96]), self-efficacy to implement
them (odds ratio = 4.25; 95% confidence interval [2.21, 8.20]), and younger age
(odds ratio = 0.97; 95% confidence interval [0.94, 1.00]). CONCLUSION: Adherence
to the Women's Preventive Services Guidelines by providers in New Mexico is
variable and, for many recommended practices, less than optimal. New targeted
implementation strategies are needed to address barriers to adherence.
PMID- 27615504
TI - Interleukin-15 enhances cytokine induced killer (CIK) cytotoxic potential against
epithelial cancer cell lines via an innate pathway.
AB - CIK cells are a subset of effector lymphocytes endowed with a non-MHC restricted
anti-tumor activity making them an appealing and promising cell population for
adoptive immunotherapy. CIK are usually generated ex-vivo by initial priming with
Interferon-gamma (IFN-gamma) and monoclonal antibody against CD3 (anti-CD3),
followed by culture in medium containing Interleukin-2 (IL-2). Interleukin-15 (IL
15) shares with IL-2 similar biological functions and recently it has been
reported to induce CIK with increased anti-leukemic potential. The aim of the
study was to compare the killing efficacy of CIK generated by IL-2 alone or IL-2
and IL-15 toward tumor targets of different origins, leukemic cells and malignant
cells from epithelial solid tumors. CIK bulk cultures were examined for cell
proliferation, surface phenotype and cytotoxic potential against tumor cell lines
K562, HL60, HeLa and MCF-7. The results showed that IL-15 is able to induce a
selective expansion of CIK cells, but it is less effective in sustaining CIK cell
proliferation compared to IL-2. Conversely, our data confirm and reinforce the
feature of IL-15 to induce CIK cells with a potent cytotoxic activity mostly
against tumor cells from epithelial solid malignancies via NKG2D-mediated
mechanism.
PMID- 27615505
TI - HLA-G profile of infertile couples who underwent assisted reproduction treatment.
AB - HLA-G codes for a non-classical class I (Ib) protein which is mainly expressed in
trophoblast cells. Many pieces of evidence pointed out its essential role
conferring immunological tolerance to the fetus. Some HLA-G alleles have been
linked to enhanced or reduced HLA-G protein levels expression, which have been
associated with reproductive failure. In this study 33 couples undergoing ART
(assisted reproduction treatment; n=66) and 120 couples who conceived naturally
(controls; n=240) were enrolled in the study. Genotyping was performed by SBT and
tagged an 1837bp at 5'URR as well as exons 2, 3 and4 of HLA-G. Alleles, genotypes
and haplotypes were compared between infertile and control groups using Fisher
Exact Test. The haplotype HLA-G*010101b/HLA-G*01:01:01 showed statistically
significant higher frequency in control groups. The immunogenetics of infertility
is complex and might be dependent on different genes involved in the
establishment of a successful pregnancy. A better understanding of HLA-G alleles
and haplotypes structure and how the genetic diversity at their regulatory sites
could impact on their level of expression and build up the susceptibility or
protection conditions may shed light on the comprehension of immunogenetics
mechanisms acting at the fetus-maternal interface.
PMID- 27615507
TI - Role of the sulfur to alpha-carbon thioether bridges in thurincin H.
AB - Thurincin H is a small protein produced by Bacillus thuringiensis SF361 with gram
positive antimicrobial properties. The toxins produced by B. thuringiensis are
widely used in the agriculture as, e.g. natural preservatives in dairy products.
The structure of thurincin H possesses four covalent sulfur to [Formula: see
text]-carbon bonds that involve the cysteine side-chains; these bonds are
probably responsible for the shape and stability of the protein and, thereby, for
its antimicrobial properties. To examine the influence of the formation of the
sulfur-carbon bonds on the folding pathways and stability of the protein, a
series of canonical and multiplexed replica-exchange simulations with the coarse
grained UNRES force field was carried out without and with distance restraints
imposed on selected S-C[Formula: see text] atom pairs. It was found that the
order of the formation and breaking of the S-C[Formula: see text] thioether bonds
significantly impacts on the foldability and stability of the thurincin H. It was
also observed that thioether bridges play a major role in stabilizing the global
fold of the protein, although it significantly diminishes the entropy of the
system. The maximum foldability of thurincin H was observed in the presence of
the optimal set of three out of four thioether bridges. Thus, the results suggest
that the presence of ThnB enzyme and other agents that catalyze the formation of
thioether bridges can be essential for correct folding of thurincin H and that
the formation of the fourth bridge does not seem to facilitate folding; instead,
it seems to rigidify the loop and prevent proteolysis.
PMID- 27615506
TI - Preemptive reduction of immunosuppression upon high urinary polyomavirus loads
improves patient survival without affecting kidney graft function.
AB - BACKGROUND: Polyomavirus (PV) is a major cause of kidney graft disease.
Monitoring by polymerase chain reaction (PCR) on blood is currently recommended.
In order to avoid irreversible lesions, we investigated the clinical impact of
preemptive reduction of immunosuppression (IS) in kidney transplant recipients
(KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC
virus. MATERIAL AND METHODS: From 2000 to 2011, in our single center, 789
consecutive KTR were distributed into 4 groups, according to the maximal Upv
levels (by PCR) during the first year and the therapeutic option: (A) Upv <104
copies (cp)/mL (n=573), (B) >=104 Upv <107 cp/mL (n=100), and (C) Upv >=107 cp/mL
(n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only,
as 14 patients (subgroup Cb) were at risk for graft rejection. RESULTS: The
preemptive reduction of IS (group Ca) increased patient survival as compared with
all other groups (P<.05), did not modify graft function, and increased graft
survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003).
Differences for risk factors are as follows (groups Ca vs A): incidence of human
leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8%
(P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute
rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in
group Ca (2% of total grafts) without effect on patient or graft outcome.
CONCLUSION: The reduction of IS in patients with high Upv loads is beneficial for
patient survival and does not affect graft survival or graft function.
PMID- 25050048
TI - Effects of Light Color on Energy Expenditure and Behavior in Broiler Chickens.
AB - This study was conducted in order to investigate whether the presence of light or
different colors of light would influence the energy expenditure and behavior of
broiler chickens. Eight 8-week-old broiler chickens were adapted to a respiration
chamber (Length, 28.5 cm; Height, 38.5 cm; Width, 44.0 cm) for one week prior to
the initiation of the experiment. In experiment 1, energy expenditure and
behavior of the chickens were analyzed in the presence or absence of light for
four days. Chickens were exposed to 6 cycles of 2 h light/2 h dark period per
day. In experiment 2, the broiler chickens that had been used in experiment 1
were used to evaluate the effect of 4 different wavelength light-emitting diodes
(LEDs) on the energy expenditure and behavior of broiler chickens. The LEDs used
in this study had the following wavelength bands; white (control), red (618 to
635 nm), green (515 to 530 nm) and blue (450 to 470 nm). The chickens were
randomly exposed to a 2-h LED light in a random and sequential order per day for
3 days. Oxygen consumption and carbon dioxide production of the chickens were
recorded using an open-circuit calorimeter system, and energy expenditure was
calculated based on the collected data. The behavior of the chickens was analyzed
based on following categories i.e., resting, standing, and pecking, and closed
circuit television was used to record these behavioral postures. The analysis of
data from experiment 1 showed that the energy expenditure was higher (p<0.001) in
chickens under light condition compared with those under dark condition. The
chickens spent more time with pecking during a light period, but they frequently
exhibited resting during a dark period. Experiment 2 showed that there was no
significant difference in terms of energy expenditure and behavior based on the
color of light (white, red, green, and blue) to which the chickens were exposed.
In conclusion, the energy expenditure and behavior of broiler chickens were found
to be strongly affected by the presence of light. On the other hand, there was no
discernible difference in their energy expenditure and behavior of broiler
chickens exposed to the different LED lights.
PMID- 27615509
TI - Leishmania infantum antigens modulate memory cell subsets of liver resident T
lymphocyte.
AB - In the recent years, the liver has been recognized as an important immune organ
with major regulatory functions and immune memory, adding to the well-described
vital metabolic functions. There are evidences from experimental infections
performed with visceral Leishmania species that immune responses to parasite
infection can be organ-specific. The liver is the compartment of acute resolving
infection, with minimal tissue damage and resistance to reinfection, whereas the
spleen is the compartment of parasite persistence. Control of hepatic infection
in mice requires a coordinated immune response that involves the development of
inflammatory granulomas. It is also described that the liver harbors populations
of resident lymphocytes, which may exhibit memory characteristics. Therefore, the
present study aims to address the role of the liver as an immune memory organ in
the context of Leishmania infantum infection, by characterizing phenotypically
resident liver T lymphocytes. The dynamics of memory T cells in L. infantum
infected BALB/c mice and the effect of anti-leishmanial treatment in the
differentiation of memory cell subsets were analyzed. The potential of
recognition, differentiation and selection of memory lymphocytes by three L.
infantum recombinant proteins were also explored. L. infantum infection generates
effector and central memory T cells, but the cells did not expand when recalled,
demonstrating a possible parasite silencing effect. The treatment with a
leishmanicidal drug (antimoniate meglumine) increases the levels of memory and
effector T cells, eliciting a more robust hepatic immune response. L. infantum
parasites with a decreased sensitivity to the leishmanicidal drug favor the
expansion of memory CD8+ T cell subset, but inhibit the proliferation of CD8+ T
effector cells, possibly assuring their own survival. The recombinant proteins
LirCyp1 and LirSOD are strongly recognized by memory cells of treated mice,
indicating that these proteins might be used in a prophylactic or therapeutic
vaccine formulation. Thus, L. infantum released antigens induce the development
of immune memory subsets in the liver resident T cell population that
specifically recognized parasite antigens, including recombinant proteins.
PMID- 27615510
TI - Evaluation of a nanotechnology-based approach to induce gene-expression in human
THP-1 macrophages under inflammatory conditions.
AB - Macrophages orchestrate the initiation and resolution of inflammation by
producing pro- and anti-inflammatory products. An imbalance in these mediators
may originate from a deficient or excessive immune response. Therefore,
macrophages are valid therapeutic targets to restore homeostasis under
inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle
effectively induces gene expression in human macrophages under inflammatory
conditions without undesirable immunogenic responses. THP-1 macrophages were
challenged with lipopolysaccharide (LPS, 5MUg/mL). Polyethylenimine (PEI)
nanoparticles grafted with a mannose receptor ligand (Man-PEI) were used as a
gene delivery method. Nanoparticle toxicity, Man-PEI cellular uptake rate and
gene induction efficiency (GFP, CD14 or CD68) were studied. Potential immunogenic
responses were evaluated by measuring the production of tumor necrosis factor
alpha (TNF-alpha), Interleukin (IL)-6 and IL-10. Man-PEI did not produce
cytotoxicity, and it was effectively up-taken by THP-1 macrophages (69%). This
approach produced a significant expression of GFP (mRNA and protein), CD14 and
CD68 (mRNA), and transiently and mildly reduced IL-6 and IL-10 levels in LPS
challenged macrophages. Our results indicate that Man-PEI is suitable for
inducing an efficient gene overexpression in human macrophages under inflammatory
conditions with limited immunogenic responses. Our promising results set the
foundation to test this technology to induce functional anti-inflammatory genes.
PMID- 27615511
TI - Association of the I148M/PNPLA3 (rs738409) polymorphism with premature coronary
artery disease, fatty liver, and insulin resistance in type 2 diabetic patients
and healthy controls. The GEA study.
AB - The aim of this study was to evaluate the potential use of the I148M/PNPLA3
(rs738409) gene polymorphism as a susceptibility marker for premature coronary
artery disease (pCAD) and/or cardiovascular risk factors in Mexican type 2
diabetes mellitus patients (T2DM). The polymorphism was genotyped by 5'
exonuclease TaqMan assays in a group of 2572 subjects (1103 with pCAD and 1469
healthy controls) belonging to the Genetics of Atherosclerotic Disease (GEA)
Mexican Study. Anthropometric and biochemical measurements were performed in all
individuals. The association between the I148M/PNPLA3 (rs738409) gene
polymorphism with pCAD and other metabolic and cardiovascular risk factors was
evaluated using logistic regression analysis under different statistical
approaches including dominant, recessive, heterozygous, additive, and co-dominant
models. The polymorphism was not associated with pCAD in the whole group of
participants, however, when patients and controls were divided into those with
and without T2DM, under additive model, the polymorphism was associated with the
presence of pCAD only in patients with T2DM (OR=1.20, 95% CI: 1.01-1.42,
Padd=0.042). On the other hand, under several models adjusted for age, gender,
body mass index and T2DM, the polymorphism was associated with increased risk of
fatty liver and elevated levels of alanine transaminase (ALT) in the whole group
of pCAD patients and controls. In the control group, the polymorphism was
associated with insulin resistance and coronary artery calcification (CAC)
score>=10 under several models. The results suggest that the I148M/PNPLA3
(rs738409) polymorphism is associated with the presence of pCAD in T2DM patients
and with some cardiometabolic parameters. The association detected with CAC in
the control group indicates that this polymorphism could be a marker for
subclinical atherosclerosis.
PMID- 27615513
TI - Dock3-NMDA receptor interaction as a target for glaucoma therapy.
AB - Glaucoma is a neurodegenerative disease of the eye and it is one of the major
causes of blindness. Glaucoma is usually associated with elevated intraocular
pressure (IOP) and the current therapy focuses on reduction of IOP. However,
neuroprotective strategies could also be beneficial for treatment of glaucoma
because the pathology of the disease involves retinal ganglion cell (RGC) death
and damage to the optic nerve. Dedicator of cytokinesis 3 (Dock3) is an atypical
guanine exchange factor (GEF) that belongs to a family of Dock proteins, Dock1
11. Dock3 exerts neuroprotective effects on the retina and optic nerve, and
studies revealed that some of the Dock3-mediated effects are GEF-independent. One
of these mechanisms is that Dock3 directly binds to the GluN2B subunit of the N
methyl-D-aspartate (NMDA) receptor. Upon stimulation by NMDA or optic nerve
crush, overexpression of Dock3 promotes internalization and degradation of the
NMDA receptor in the retina in vivo. It is suggested that this process is
mediated by inhibition of Fyn, a Src family tyrosine kinase. Reduction in NMDA
receptor expression results in decreased excitotoxic damage and oxidative stress,
thereby promoting RGC survival. In this review, we discuss the therapeutic
potential of neuroprotection for glaucoma and the effects of Dock3 on NMDA
receptors. We also discuss apoptosis signal-regulating kinase 1 (ASK1), a member
of mitogen-activated protein kinase kinase kinase that is a key regulator of
cellular responses to oxidative stress, as an innovative therapeutic target for
glaucoma.
PMID- 27615512
TI - Phase correlation imaging of unlabeled cell dynamics.
AB - We present phase correlation imaging (PCI) as a novel approach to study cell
dynamics in a spatially-resolved manner. PCI relies on quantitative phase imaging
time-lapse data and, as such, functions in label-free mode, without the
limitations associated with exogenous markers. The correlation time map outputted
in PCI informs on the dynamics of the intracellular mass transport. Specifically,
we show that PCI can extract quantitatively the diffusion coefficient map
associated with live cells, as well as standard Brownian particles. Due to its
high sensitivity to mass transport, PCI can be applied to studying the integrity
of actin polymerization dynamics. Our results indicate that the cyto-D treatment
blocking the actin polymerization has a dominant effect at the large spatial
scales, in the region surrounding the cell. We found that PCI can distinguish
between senescent and quiescent cells, which is extremely difficult without using
specific markers currently. We anticipate that PCI will be used alongside
established, fluorescence-based techniques to enable valuable new studies of cell
function.
PMID- 27615514
TI - Proximity Labeling Reveals Molecular Determinants of FGFR4 Endosomal Transport.
AB - The fibroblast growth factor receptors (FGFRs) are important oncogenes promoting
tumor progression in many types of cancer, such as breast, bladder, and lung
cancer as well as multiple myeloma and rhabdomyosarcoma. However, little is known
about how these receptors are internalized and down-regulated in cells. We have
here applied proximity biotin labeling to identify proteins involved in FGFR4
signaling and trafficking. For this purpose we fused a mutated biotin ligase,
BirA*, to the C-terminal tail of FGFR4 (FGFR4-BirA*) and the fusion protein was
stably expressed in U2OS cells. Upon addition of biotin to these cells, proteins
in proximity to the FGFR4-BirA* fusion protein became biotinylated and could be
isolated and identified by quantitative mass spectrometry. We identified in total
291 proteins, including 80 proteins that were enriched in samples where the
receptor was activated by the ligand (FGF1), among them several proteins
previously found to be involved in FGFR signaling (e.g., FRS2, PLCgamma, RSK2 and
NCK2). Interestingly, many of the identified proteins were implicated in
endosomal transport, and by precise annotation we were able to trace the
intracellular pathways of activated FGFR4. Validating the data by confocal and
three-dimensional structured illumination microscopy analysis, we concluded that
FGFR4 uses clathrin-mediated endocytosis for internalization and is further
sorted from early endosomes to the recycling compartment and the trans-Golgi
network. Depletion of cells for clathrin heavy chain led to accumulation of FGFR4
at the cell surface and increased levels of active FGFR4 and PLCgamma, while AKT
and ERK signaling was diminished, demonstrating that functional clathrin-mediated
endocytosis is required for proper FGFR4 signaling. Thus, this study reveals
proteins and pathways involved in FGFR4 transport and signaling that provide
possible targets and opportunities for therapeutic intervention in FGFR4 aberrant
cancer.
PMID- 27615515
TI - Video-game based exercises for older people with chronic low back pain: a
protocol for a feasibility randomised controlled trial (the GAMEBACK trial).
AB - OBJECTIVES: To investigate the feasibility of implementing a video-game exercise
programme for older people with chronic low back pain (LBP). DESIGN: Single
centred single-blinded randomised controlled trial (RCT). SETTING: Physiotherapy
outpatient department in a public hospital in Western Sydney, Australia.
PARTICIPANTS: We will recruit 60 participants over 55 years old with chronic LBP
from the waiting list. INTERVENTIONS: Participants will be randomised to receive
video-game exercise (n=30) or to remain on the waiting list (n=30) for 8 weeks,
with follow up at 3 and 6 months. Participants engaging in video-game exercises
will be unsupervised and will complete video-game exercise for 60minutes, 3 times
per week. Participants allocated to remain on the waiting list will be encouraged
to maintain their usual levels of physical activity. MAIN OUTCOME MEASURE: The
primary outcomes for this feasibility study will be study processes (recruitment
and response rates, adherence to and experience with the intervention, and
incidence of adverse events) relevant to the future design of a large RCT.
Estimates of treatment efficacy (point estimates and 95% confidence intervals) on
pain self-efficacy, care seeking, physical activity, fear of movement/re-injury,
pain, physical function, disability, falls-efficacy, strength, and walking speed,
will be our secondary outcome measures. RESULTS: Recruitment for this trial began
in November 2015. CONCLUSION: This study describes the rationale and processes of
a feasibility study investigating a video-game exercise programme for older
people with chronic LBP. Results from the feasibility study will inform on the
design and sample required for a large multicentre RCT. TRIAL REGISTRATION:
Australian New Zealand Clinical Trials Registry: ACTRN12615000703505.
PMID- 27615516
TI - Viral gastrointestinal infections and norovirus genotypes in a paediatric UK
hospital, 2014-2015.
AB - BACKGROUND: Diarrhoea in children is a common disease; understanding the
incidence of causative viruses can aid infection control and vaccine development.
OBJECTIVES: Describe the incidence and characteristics of gastroenteric viruses
including norovirus genotypes in a paediatric hospital cohort. STUDY DESIGN:
Norovirus, adenovirus, sapovirus, astrovirus, rotavirus qPCR and norovirus
genotyping results for all stool specimens (n=4786; 1393 patients) at a UK
paediatric tertiary referral hospital June 2014-July 2015. RESULTS AND
DISCUSSION: 24% (329/1393) of patients were positive for a GI virus; the majority
were positive for norovirus (44%, 144/329) or adenovirus (44%, 146/329). The
overall incidence of rotavirus (2%) is reduced compared to pre-vaccination
studies; however the incidence of other GI viruses has not increased. Norovirus
infections had a significantly higher virus burden compared to other GI viruses
(P <=0.03); sapovirus infections had the lowest viral burden. The number of
norovirus cases per month did not follow the typical winter seasonal trend of
nationally reported outbreaks. The number of cases per month correlates with the
number of hospital admissions (R=0.703, P=0.011); the number of admissions
accounts for 50% of the variability in number of cases per month. The breadth of
genotypes seen (48% non-GII.4), suggests a community source for many norovirus
infections and has implications for vaccine development. All GI viruses caused
chronic infections, with the majority (50-100%) in immunocompromised patients.
Incidence or duration of infection in chronic norovirus infections did not differ
between genotypes, suggesting host-mediated susceptibility.
PMID- 27615517
TI - Tyrosine kinase 2 is not limiting human antiviral type III interferon responses.
AB - Tyrosine kinase 2 (TYK2) associates with interferon (IFN) alpha receptor, IL-10
receptor (IL-10R) beta and other cytokine receptor subunits for signal
transduction, in response to various cytokines, including type-I and type-III
IFNs, IL-6, IL-10, IL-12 and IL-23. Data on TYK2 dependence on cytokine responses
and in vivo consequences of TYK2 deficiency are inconsistent. We investigated a
TYK2 deficient patient, presenting with eczema, skin abscesses, respiratory
infections and IgE levels >1000 U/mL, without viral or mycobacterial infections
and a corresponding cellular model to analyze the role of TYK2 in type-III IFN
mediated responses and NK-cell function. We established a novel simple diagnostic
monocyte assay to show that the mutation completely abolishes the IFN-alpha
mediated antiviral response. It also partly reduces IL-10 but not IL-6 mediated
signaling associated with reduced IL-10Rbeta expression. However, we found almost
normal type-III IFN signaling associated with minimal impairment of virus control
in a TYK2 deficient human cell line. Contrary to observations in TYK2 deficient
mice, NK-cell phenotype and function, including IL-12/IL-18 mediated responses,
were normal in the patient. Thus, preserved type-III IFN responses and normal NK
cell function may contribute to antiviral protection in TYK2 deficiency leading
to a surprisingly mild human phenotype.
PMID- 27615518
TI - Possible Evidence for a New Form of Liquid Buried in the Surface Tension of
Supercooled Water.
AB - Contrary to the historical data, several recent experiments indicate that the
surface tension of supercooled water follows a smooth extrapolation of the IAPWS
equation in the supercooled regime. It can be seen, however, that a small
deviation from the IAPWS equation is present in the recent experimental
measurements. It is shown with simulations using the WAIL water potential that
the small deviation in the experimental data is consistent with the tail of an
exponential growth in surface tension as temperature decreases. The emergence
temperature, Te, of a substantial deviation from the IAPWS equation is shown to
be 227 K for the WAIL water and 235 K for real water. Since the 227 K Te is close
to the Widom line in WAIL water, we argue that real water at 235 K approaches a
similar crossover line at one atmospheric pressure.
PMID- 27615519
TI - Broadband metasurface holograms: toward complete phase and amplitude engineering.
AB - As a revolutionary three-dimensional imaging technique, holography has attracted
wide attention for its ability to photographically record a light field. However,
traditional phase-only or amplitude-only modulation holograms have limited image
quality and resolution to reappear both amplitude and phase information required
of the objects. Recent advances in metasurfaces have shown tremendous
opportunities for using a planar design of artificial meta-atoms to shape the
wave front of light by optimal control of both its phase and amplitude. Inspired
by the concept of designer metasurfaces, we demonstrate a novel amplitude-phase
modulation hologram with simultaneous five-level amplitude modulation and eight
level phase modulation. Such a design approach seeks to turn the perceived
disadvantages of the traditional phase or amplitude holograms, and thus enable
enhanced performance in resolution, homogeneity of amplitude distribution,
precision, and signal-to-noise ratio. In particular, the unique holographic
approach exhibits broadband characteristics. The method introduced here delivers
more degrees of freedom, and allows for encoding highly complex information into
designer metasurfaces, thus having the potential to drive next-generation
technological breakthroughs in holography.
PMID- 27615521
TI - Time for reflection.
PMID- 27615522
TI - #hellomynameis at the University of Northampton.
PMID- 27615520
TI - Local and thalamic origins of correlated ongoing and sensory-evoked cortical
activities.
AB - Thalamic inputs of cells in sensory cortices are outnumbered by local
connections. Thus, it was suggested that robust sensory response in layer 4
emerges due to synchronized thalamic activity. To investigate the role of both
inputs in the generation of correlated cortical activities, we isolated the
thalamic excitatory inputs of cortical cells by optogenetically silencing
cortical firing. In anaesthetized mice, we measured the correlation between
isolated thalamic synaptic inputs of simultaneously patched nearby layer 4 cells
of the barrel cortex. Here we report that in contrast to correlated activity of
excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit
lower variability and asynchronous spontaneous and sensory-evoked inputs. These
results are further supported in awake mice when we recorded the excitatory
inputs of individual cortical cells simultaneously with the local field potential
in a nearby site. Our results therefore indicate that cortical synchronization
emerges by intracortical coupling.
PMID- 27615523
TI - Reducing avoidable deaths from failure to rescue: a discussion paper.
AB - AIM: This article proposes a radical new approach to the monitoring and
governance of services, and the education and training of nurses to meet 'failure
to rescue' requirements. BACKGROUND: Healthcare policy in the UK that seeks to
ensure safe and effective services for the acutely ill has largely failed,
resulting in adult patients dying unnecessarily. Despite grand rhetoric, UK
governments have distanced themselves from implementation, resulting in patchy
localised developments and creating inconsistent service responses. DESIGN AND
DATA SOURCES: This article draws on a review of research and UK policy literature
and best international practice to propose a new national framework approach that
combines competency development, governance and performance monitoring to address
'failure to rescue' shortcomings. IMPLICATIONS FOR NURSING: Paramount is a
nationally agreed and fit-for-purpose competency tool using simulation to assess
staff in order to improve recognition of the deteriorating patient. Service
improvements should include increased investment in telemedicine; service
performance should be communicated through publicly available ratings and
overseen by patient panels; and governance will require strengthening through
enhanced Care Quality Commission/Monitor input, which should be linked to the
maintenance of foundation trust status. CONCLUSION: Health professional bodies,
regulators, providers and the Government must work together to strengthen the
safety and effectiveness of acute services. This will require investment in staff
competency and enhancement of the governance to ensure services consistently meet
public expectations and reduce unnecessary deaths.
PMID- 27615524
TI - Citrate anticoagulation in the ICU: the Leeds experience.
AB - Continuous renal replacement therapy (CRRT) is widely used in the management of
critically ill patients with acute kidney injury. It requires effective
anticoagulation of the extracorporeal blood circuit. Although heparin is the most
commonly prescribed anticoagulant, there are issues associated with heparin, and
there has been increasing interest in regional citrate anticoagulation as an
alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from
heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across
the Trust. This article examines the reasons for the switch, the implementation
of citrate and the impact of this quality-improvement project in terms of patient
outcome data and feedback from the ICU nursing team.
PMID- 27615525
TI - The nurse's role in delivering the Global Safe Surgery Campaign.
AB - Chris Carter, Defence School of Healthcare Education, Birmingham City University
discusses his involvement in a project to support critical care nursing in
Zambia.
PMID- 27615526
TI - Getting up to speed: adjusting to the pace of accident and emergency.
AB - Michelle Gracia, Second Year Student Nurse (Adult), School of Health Studies,
Gibraltar Health Authority looks reflects on the importance of communication with
patients and colleagues.
PMID- 27615527
TI - Female genital mutilation: what do we know so far?
AB - Female genital mutilation (FGM) is a practice that is now familiar to UK health
professionals. It continues to be a problem in high-risk populations and affects
girls and women throughout their lives. Complications related to FGM are poorly
reported and documented. Health professionals, therefore, must be aware of the
adverse effects and how they affect obstetric, gynaecological and sexual function
and general quality of life. They must also be sensitive towards the
psychological and emotional issues relating to FGM. Sociocultural barriers make
research and data-collection difficult in a cohort of women who prefer not to
discuss or disclose such intimate issues. New guidelines on the management of
health consequences in FGM have been published, but evidence is of poor quality.
PMID- 27615528
TI - Improving the service for patients receiving extracorporeal photopheresis using
Lean principles.
AB - The photopheresis unit where the authors work has seen an increased demand both
locally and as an outreach service. A Lean assessment of the unit was undertaken
to improve processing time and productivity, which in turn would improve the
availability of treatment and improve patient care. The assessment indicated that
there were excellent nursing standards and patient care; however, patient waiting
times and treatment times were prolonged in comparison with other units. The unit
reviewed the patient pathway and identified where delays occurred and
consequently changed patient scheduling.
PMID- 27615529
TI - Using health psychology to help patients: theories of behaviour change.
AB - Behaviour change theories and related research evidence highlight the complexity
of making and sticking to health-related behaviour changes. These theories make
explicit factors that influence behaviour change, such as health beliefs, past
behaviour, intention, social influences, perceived control and the context of the
behaviour. Nurses can use this information to understand why a particular patient
may find making recommended health behaviour changes difficult and to determine
factors that may help them. This article outlines five well-established theories
of behaviour change: the health belief model, the theory of planned behaviour,
the stages of change model, self-determination theory, and temporal self
regulation theory. The evidence for interventions that are informed by these
theories is then explored and appraised. The extent and quality of evidence
varies depending on the type of behaviour and patients targeted, but evidence
from randomised controlled trials indicates that interventions informed by theory
can result in behaviour change.
PMID- 27615530
TI - Memories of Nursing: an oral history.
PMID- 27615531
TI - Does cheating by students undermine the integrity of the nursing profession?
AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
the worrying media reports that suggest that large numbers of student nurses are
cheating their way onto the professional register.
PMID- 27615532
TI - Child safeguarding: the NHS can do much more.
AB - John Tingle, Reader in Health Law at Nottingham Trent University, discusses the
Care Quality Commission's review of the arrangements for child safeguarding and
health care for looked-after children in England.
PMID- 27615533
TI - Reflective writing: a user-friendly guide.
AB - Stephen Hamilton, Nurse Education Consultant, Business Services Organisation. In
this piece, he outlines the nature of the process of reflection to allay concerns
that registered nurses may have about the process, as well as dispel any myths
surrounding the purpose of reflection.
PMID- 27615534
TI - From staff nurse to nurse consultant.
AB - John Fowler, independent education consultant, continues to explore the
importance of leadership for clinically based nurses.
PMID- 27615535
TI - Like it or not, the way we look matters.
AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, discusses the
tricky issue of dress codes, tattoos and piercings in the NHS after some high
profile media stories thrust the issue into the limelight.
PMID- 27615536
TI - Understanding immunotherapy for the treatment of non-small cell lung cancer.
AB - Patients diagnosed with advanced non-small-cell lung cancer (NSCLC) (either
squamous or non-squamous) have previously had limited treatment options after
progression on chemotherapy. With the emergence of new drugs, particularly in the
immuno-oncology setting, this is now changing. Recent clinical trial evidence
demonstrates that compared with docetaxel, patients who received nivolumab had
better overall survival and also significantly fewer grade 3-4 adverse events.
This article reviews the clinical trial data for nivolumab and provides an
overview of how this drug works. The adverse event profile of nivolumab is
assessed and compared to that of docetaxel. The important role that nurses can
play in supporting patients on nivolumab is also discussed.
PMID- 27615537
TI - Multiple myeloma: managing a complex blood cancer.
AB - This article gives a comprehensive overview of multiple myeloma (MM), a complex
blood cancer involving overproduction of plasma cells. Although MM remains
incurable, patients are living longer as a result of multiple treatment options.
However, MM patients are also living with a higher symptom burden. The overall
aims in managing MM are therefore to control disease progression, prolong
survival and improve quality of life.
PMID- 27615538
TI - Promoting safety and progress.
PMID- 27615539
TI - A continuing force for good.
PMID- 27615540
TI - Patient-practitioner perception gap in treatment-induced nausea and vomiting.
AB - This UK cohort analysis of a European survey evaluated the differences between
health professionals and cancer patients regarding the perceived incidence,
impact and drug management of chemotherapy/radiotherapy-induced nausea/vomiting
(CINV/RINV). The UK healthcare system is unique in that it has dedicated oncology
clinical nurse specialists. The analysis found that more patients experienced
nausea following their most recent treatment cycle than vomiting. Health
professionals overestimated the incidence of CINV/RINV but underestimated its
impact on patients' daily lives, particularly in cases of mild and moderate
nausea/vomiting. The level of antiemetic cover initiated and degree of symptom
control was often suboptimal. Patients under-reported symptoms, primarily because
they considered nausea/vomiting an inevitable side effect of treatment.
Altogether, 42% of patients reported full adherence to their antiemetic regimen.
Leading factors for non-adherence included not having a 'preventive mindset', low
symptom severity and a reluctance to increase pill burden. In conclusion, there
is a perceptual gap between health professionals and patients around experiences
of CINV/RINV. Advances in management depend on enhancing health professional
patient communication, and reporting and understanding nausea as a distinct
issue.
PMID- 27615541
TI - Dynamic cue use in pigeon mid-session reversal.
AB - The systematic anticipation and preservation errors produced by pigeons around
the reversal point in midsession reversal (MSR) learning experiments suggest that
an internal time estimation cue, instead of a more efficient external cue
provided by reinforcement, controls behavior over the course of a session. The
current experiments examined the role and effectiveness of other external cues in
the MSR task. In Experiment 1, providing differential outcomes based on response
key location produced fewer errors prior to, but not after, the reversal as
compared with a non-differential outcomes condition. Experiment 2a used
alternating differentially colored ITIs (cued sessions) or dark ITIs (un-cued
sessions) during each half of the session. The ITI cues improved switch
efficiency both prior to and after the reversal. Experiment 2b introduced probe
trials around the reversal, testing ITI color cues added to un-cued sessions or
removed from cued sessions. Results showed control by the ITI cues when they were
available and control by the time-based cue when they were unavailable. This
suggests both cues were being simultaneously processed when available and that
the cues could also independently provide sufficient information about future
reinforcement. In Experiment 2c, ITI cues were inserted as probe trials in the
opposite half of the session (miscues). The closer such miscue trials were to the
reversal, the more the ITI cues exerted control over behavior. Together, these
results indicate that as the utility of internal temporal cues is reduced, the
use of external visual cues increases. These results have implications for the
way in which cues dynamically shift in controlling behavior over time based on
their relative rates of utility, and are discussed in light of an occasion
setting perspective.
PMID- 27615542
TI - A randomized nutrition counseling intervention in pediatric leukemia patients
receiving steroids results in reduced caloric intake.
AB - BACKGROUND: Quality of life in survivors of pediatric acute lymphocytic leukemia
(ALL) can be compromised by chronic diseases including increased risk of second
cancers, cardiovascular disease, and diabetes. Overweight or obesity further
increases these risks. Steroids are a component of chemotherapy for ALL, and
weight gain is a common side effect. To impact behaviors associated with weight
gain, we conducted a randomized nutrition counseling intervention in ALL patients
on treatment. PROCEDURE: ALL patients on a steroid-based treatment regimen at the
MD Anderson Children's Cancer Hospital were recruited and randomized into control
or intervention groups. The control group received standard care and nutrition
education materials. The intervention group received monthly one-on-one nutrition
counseling sessions, consisting of a baseline and 12 follow-up visits.
Anthropometrics, dietary intake (3-day 24-hr dietary recalls) and oxidative
stress measures were collected at baseline, 6 months, and postintervention.
Dietary recall data were analyzed using the Nutrition Data System for Research.
RESULTS: Twenty-two patients (median age 11.5 years), all in the maintenance
phase of treatment, were recruited. The intervention group (n = 12) reported
significantly lower calorie intake from baseline to 12-month follow-up and
significant changes in glutamic acid and selenium intake (P < 0.05). Waist
circumference was significantly associated with calorie, vitamin E, glutamic
acid, and selenium intake. CONCLUSIONS: A year-long dietary intervention was
effective at reducing caloric intake in pediatric ALL patients receiving steroid
based chemotherapy, indicating that this is a modality that can be built upon for
obesity prevention and management.
PMID- 27615544
TI - 4(th) Mediterranean Multidisciplinary Course on Iron Anemia April 29(th)-30(th)
2016, Madrid, Spain.
PMID- 27615543
TI - Deregulated matriptase activity in oral squamous cell carcinoma promotes the
infiltration of cancer-associated fibroblasts by paracrine activation of protease
activated receptor 2.
AB - Cancer-associated fibroblasts (CAFs) are known to contribute to cancer
progression. We have reported that cell surface expression of hepatocyte growth
factor activator inhibitor 1 (HAI-1) is decreased in invasive oral squamous cell
carcinoma (OSCC) cells. This study examined if HAI-1-insufficiency contributes to
CAF recruitment in OSCC. Serum-free conditioned medium (SFCM) from a human OSCC
line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB,
MRC5 and KD. SFCM from HAI-1-knockdown SAS showed an additive effect on the
migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease-activated
receptor-2 (PAR-2) expression in NB1RGB and MRC5, but not in KD, and a PAR-2
antagonist blocked the stimulatory effect of HAI-1 knockdown on migration of the
PAR-2 expressing cell lines. Moreover, HAI-1-deficient SFCM showed additive
stimulatory effects on the migration of wild-type but not PAR-2-deficient mouse
fibroblasts. Therefore, the enhanced migration induced by HAI-1-insufficiency was
mediated by PAR-2 activation in fibroblasts. This activation resulted from the
deregulation of the activity of matriptase, a PAR-2 agonist protease. HAI-1 may
thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI
1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by
paracrine activation of fibroblast PAR-2. Immunohistochemical analysis of
resected OSCC revealed increased PAR2-positive CAFs in 35% (33/95) of the cases
studied. The increased PAR-2 positive CAFs tended to correlate with infiltrative
histology of the invasion front and shorter disease-free survival of the
patients.
PMID- 27615545
TI - Pre- and postoperative atrial fibrillation in CABG patients have similar
prognostic impact.
AB - OBJECTIVES: To study pre- and postoperative atrial fibrillation and its long-term
effects in a cohort of aortocoronary bypass surgery patients. DESIGN: Altogether
615 patients undergoing aortocoronary bypass graft surgery in 1999-2000 were
studied. Forty-four (7%) had preoperative atrial fibrillation. Postoperative
atrial fibrillation occurred in 165/615 patients (27%) while 406/615 patients
(66%) had no atrial fibrillation. After a median follow-up of 15 years, symptoms
and medication in survivors were recorded, and cause of death in the deceased was
obtained. RESULTS: Death due to cerebral ischaemia was most common in the pre-
and postoperative atrial fibrillation groups (7% and 5%, respectively, v. 2%
among those without atrial fibrillation, p = .038), as were death due to heart
failure (18% and 14%, v. 7%, p = .007) and sudden death (9% and 5%, v. 2%, p =
.029). The presence of pre- or postoperative atrial fibrillation was an
independent risk factor for late mortality (hazard ratios 1.47 (1.02-2.12) and
1.28 (1.01-1.63), respectively). CONCLUSIONS: Patients with pre- or postoperative
atrial fibrillation undergoing aortocoronary bypass surgery have increased long
term mortality and risk of cerebral ischemic and cardiovascular death compared
with patients in sinus rhythm.
PMID- 27615546
TI - Burn-associated bloodstream infections in pediatric burn patients: Time
distribution of etiologic agents.
AB - BACKGROUND: Infections are the leading cause of morbidity and mortality in
patients with burns in burn units. Bloodstream infections (BSIs) in patients with
burns may result from burn wound infection, use of invasive devices such as
central venous catheters, and translocation of the gastrointestinal flora.
OBJECTIVE: In this study, we investigated the distribution and antimicrobial drug
resistance of causative pathogens in children with burns and the durational
changes of microorganisms in the distribution of BSIs in children. METHODS: This
study was conducted at the Pediatric Burn Unit (PBU) of Dr. Behcet Uz Children
Research and Training Hospital during the period of November 2008-April 2015. The
study subjects were all the patients admitted to the PBU, in whom microorganisms
were isolated at least from one of the cultures, including blood and catheter
cultures. RESULTS: Gram-positive bacteria were the most common causative agents
of BSI in patients with burns (66.4%), followed by gram-negative bacteria (22.1%)
and fungi (11.5%). The median duration of development of BSIs caused by gram
positive bacteria from the time of burn was 5 days (ranging from 2 to 54 days of
burn), which was significantly shorter than that of BSIs caused by gram-negative
bacteria (12 days) and fungal pathogens (13 days). CONCLUSION: The etiologic
agents of BSIs in children may differ from those in adults. Gram-negative drug
resistant bacteria such as multidrug-resistant Pseudomonas aeruginosa and
Acinetobacter baumannii were important agents of BSI in patients with burns,
especially in the long term; however, gram-positive bacteria should also be
considered while deciding the antimicrobial therapy, especially in the early
periods of burn.
PMID- 27615547
TI - Genome-wide association studies identify susceptibility loci affecting
respiratory disease in Chinese Erhualian pigs under natural conditions.
AB - Prevalence of swine respiratory disease causes poor growth performance in and
serious economic losses to the swine industry. In this study, a categorical trait
of enzootic pneumonia-like (EPL) score representing the infection gradient of a
respiratory disease, more likely enzootic pneumonia, was recorded in a herd of
332 Chinese Erhualian pigs. According to their EPL scores and the disease effect
on weight gains, these pigs were grouped into controls (EPL score <= 1) and cases
(EPL score > 1). The weight gain of the case group reduced significantly at days
180, 210, 240 and 300 as compared to the control group. The heritability of EPL
score was estimated to be 0.24 based on the pedigree information using a linear
mixed model. All 332 Erhualian pigs and their nine sire parents were genotyped
with Illumina Porcine 60K SNP chips. Two genome-wide association studies were
performed under a generalized linear mixed model and a case-control model
respectively. In total, five loci surpassed the suggestive significance level (P
= 2.98 * 10-5 ) on chromosomes 2, 8, 12 and 14. CXCL6, CXCL8, KIT and CTBP2 were
highlighted as candidate genes that might play important roles in determining
resistance/susceptibility to swine EP-like respiratory disease. The findings
advance understanding of the genetic basis of resistance/susceptibility to
respiratory disease in pigs.
PMID- 27615549
TI - Understanding patient experiences with scarring alopecia: a qualitative study
with management implications.
AB - INTRODUCTION: Alopecia can have a significant negative impact on patient's lives.
The objective of this study is to describe some of the emotional and
psychological challenges that affect women with scarring alopecia (SA). METHODS:
A qualitative study design was used with open-ended, individual interviews with
10 women with biopsy-proven SA. Interviews were audio-taped, transcribed verbatim
and analyzed thematically using ATLAS.ti analysis software. RESULTS: Four
overarching major themes (with several subthemes) emerged including the
following: the negative emotional impact of SA, difficulties with concealing hair
loss, negative experiences with diagnosis/management, and the importance of
support from others. Patients reported that many of these issues were under
emphasized during doctor visits. CONCLUSION: Analysis of patient responses
indicated that patients with SA contend with significant emotional and
psychological sequelae of their diagnosis.
PMID- 27615550
TI - Current trends in antithyroid drug treatment of Graves' disease.
AB - INTRODUCTION: Graves' hyperthyroidism is associated with significant morbidity
and mortality risk. The thionamides, methimazole, its pro-drug derivative
carbimazole, and propylthiouracil, remain a cornerstone of management. Yet
despite decades of use, optimal strategies for maximising treatment response and
curtailing adverse effect risk remains uncertain. AREAS COVERED: We reviewed the
current literature on the evidence based medical management of Graves' disease.
Specifically, we evaluated current approaches to the use of thionamides,
adjunctive therapies, and potential novel agents for controlling Graves'
hyperthyroidism. EXPERT OPINION: Primary medical therapy is successful in less
than 50% of cases and so careful selection of patients for medical treatment
based on a combination of pathological and pragmatic considerations is essential.
Carbimazole or methimazole is the treatment of choice in the non-pregnant
population driven by its more favourable pharmacokinetic and adverse effect
profile over propylthiouracil. In pregnancy the choice of treatment is less
straightforward and an approach that minimises undue fetal exposure to all
thionamides should be adopted. Additional data is needed on the value of
adjunctive therapies including potassium perchlorate, iodides, glucocorticoids,
lithium, and cholestyramine. Novel agents directed against pathogenetic targets
including TSH receptor blocking monoclonal antibodies and small molecule
antagonists may hold promise for the future.
PMID- 27615551
TI - Valve Tissue Engineering with Living Absorbable Threads.
AB - Tissue engineering (TE) depends on the population of scaffolds with appropriate
cells, arranged in a specific physiological direction using a variety of
techniques. Here, a novel technique of creating "living threads" is described
based on thin (poly(epsilon-caprolactone) fibers of different diameters (23-243
MUm). The fibers readily attract human mesenchymal stem cells (MSCs), which are
firmly adhered. These versatile fibers can be used to produce dimensional shapes
identical in shape to the cup-like structure of a normal human valve, while
preserving the specific orientation of both the cells and the fibers. The MSCs on
leaflets and the cells cultured in flask shown similar epitopes expression when
analyzed by fluorescence activated cell sorting. Together, these characteristics
have important functional implications as living absorbable fibers can be a
valuable resource in TE of living tissues, including heart valves.
PMID- 27615548
TI - Overcome tumor heterogeneity-imposed therapeutic barriers through convergent
genomic biomarker discovery: A braided cancer river model of kidney cancer.
AB - Tumor heterogeneity, encompassing genetic, epigenetic, and microenvironmental
variables, is extremely complex and presents challenges to cancer diagnosis and
therapy. Genomic efforts on genetic intratumor heterogeneity (G-ITH) confirm
branched evolution, support the trunk-branch cancer model, and present a
seemingly insurmountable obstacle to conquering cancers. G-ITH is conspicuous in
clear cell renal cell carcinoma (ccRCC), where its presence complicates
identification and validation of biomarkers and thwarts efforts in advancing
precision cancer therapeutics. However, long-term clinical benefits on targeted
therapy are not uncommon in metastatic ccRCC patients, implicating that there are
underlying constraints during ccRCC evolution, which in turn force a nonrandom
sequence of parallel gene/pathway/function/phenotype convergence within
individual tumors. Accordingly, we proposed a "braided cancer river model"
depicting ccRCC evolution, which deduces cancer development based on multiregion
tumor genomics of exceptional mTOR inhibitor (mTORi) responders. Furthermore, we
employ an outlier case to explore the river model and highlight the importance of
"Five NGS Matters: Number, Frequency, Position, Site and Time" in assessing
cancer genomics for precision medicine. This mutable cancer river model may
capture clinically significant phenotype-convergent events, predict
vulnerability/resistance mechanisms, and guide effective therapeutic strategies.
Our model originates from studying exceptional responders in ccRCC, which
warrants further refinement and future validation concerning its applicability to
other cancer types. The goal of this review is employing kidney cancer as an
example to illustrate critical issues concerning tumor heterogeneity.
PMID- 27615552
TI - Genetic diversity and pathogenic potential of low pathogenic H7 avian influenza
viruses isolated from wild migratory birds in Korea.
AB - To detect the circulation of H7 avian influenza viruses, we characterized H7
viruses found in migratory birds and live poultry markets of South Korea from
2005 to 2014. Phylogenic analysis revealed that while all viruses clustered into
the Eurasian-lineage of H7 avian viruses, at least 12 distinct genotypes were
represented. Most H7 viruses contained at least one gene segment from the highly
pathogenic A/Sck/Hong Kong/YU100/02(H5N1)-like avian virus, and they could be
separated into at least two antigenic groups. Although we did not detect
genetically identical strains, HI assay demonstrated close cross-reactivity of
some isolates with the H7N9 viruses from China. Animal studies revealed that most
of the genotypes could replicate in the lungs of mice and chickens without prior
adaptation and some, particularly H7N4 and H7N7 subtypes, induced mortality in
mice. These results reinforce growing pandemic concerns regarding recent H7
viruses and emphasize the importance of continued surveillance of avian influenza
viruses in the wild.
PMID- 27615553
TI - Fowl adenovirus species C serotype 4 is attributed to the emergence of hepatitis
hydropericardium syndrome in chickens in China.
AB - Since July in 2015, an emerging infectious disease of Hepatitis-Hydropericardium
syndrome (HHS) was prevalent in chicken flocks in China. To confirm the causative
agent and investigate the epidemiology of the disease, a total of 38 chicken
flocks including 187 samples from Jilin, Liaoning, Heilongjiang, Henan, Anhui,
Hubei, Jiangxi, Xinjiang, Shandong and Hunan provinces in China were collected
and determined by PCR detection, sequencing, phylogenetic analysis and virus
isolation. 81 samples (positive rate of samples, 81/187, 43.3%) distributed in 33
chicken flocks (positive rate of chicken flocks, 33/38, 86.8%) were detected to
be positive for fowl adenovirus (FAdV) by PCR method, of which 30 were determined
as FAdV species C, 41 were species D, 9 were species E and 1 was uncertain for
the viral species by phylogenetic analysis, implicating that at least three
species (C, D and E) of FAdVs were prevalent in China and the species C and D
were predominantly the prevalent viral strains. Interestingly, our results
indicated that two types of FAdVs (C and D) co-existed in one flock, resulting in
complex condition for the prevalence of the disease. In addition, 13 viral
strains of FAdV-C were isolated from different geographic areas and one of the
isolates from Henan province, designated HN/151025 strain, was inoculated into 40
day-old specific pathogen free chickens via intramuscular or oral route to
evaluate the pathogenicity. It was found that 90% (9/10) chickens died in the
intramuscular injection group and 30% (3/10) birds died in the oral route
infection group after challenge. Histopathology examination displayed that the
pathology confined to liver, kidney, spleen, and heart. These results indicated
that the virus was a highly virulent strain.
PMID- 27615554
TI - Geographical and seasonal variation in the intensity of sexual selection in the
barn swallow Hirundo rustica: a meta-analysis.
AB - Sexual selection arises from competition among individuals for access to mates,
resulting in the evolution of conspicuous sexually selected traits, especially
when inter-sexual competition is mediated by mate choice. Different sexual
selection regimes may occur among populations/subspecies within the same species.
This is particularly the case when mate choice is based on multiple sexually
selected traits. However, empirical evidence supporting this hypothesis at the
among-populations level is scarce. We conducted a meta-analysis of the intensity
of sexual selection on the largest database to date for a single species, the
barn swallow (Hirundo rustica), relying on quantitative estimates of sexual
selection. The intensity of sexual selection was expressed as the strength
(effect size) of the relationships between six plumage ornaments (tail length,
tail asymmetry, size of white spots on tail, ventral plumage colour, throat
plumage colour and throat patch size) and several fitness proxies related to
reproduction, parental care, offspring quality, arrival date from spring
migration, and survival. The data were gathered for four geographically separated
subspecies (H. r. rustica, H. r. erythrogaster, H. r. gutturalis, H. r.
transitiva). The overall mean effect size (Zr = 0.214; 95% confidence interval =
0.175-0.254; N = 329) was of intermediate magnitude, with intensity of sexual
selection being stronger in males than in females. Effect sizes varied during the
breeding cycle, being larger before egg deposition, when competition for access
to mates reaches its maximum (i.e. in the promiscuous part of the breeding
cycle), and decreasing thereafter. In addition, effect sizes from experiments
were not significantly larger than those from correlative studies. Finally,
sexual selection on different sexually dimorphic traits varied among subspecies.
This last result suggests that morphological divergence among populations has
partly arisen from divergent sexual selection, which may eventually lead to
speciation.
PMID- 27615555
TI - Targeting acute myeloid leukemia with TP53-independent vosaroxin.
AB - Vosaroxin is a quinolone compound that intercalates DNA and induces TP53
independent apoptosis, demonstrating activity against acute myeloid leukemia
(AML) in Phase I-III trials. Here, we examine vosaroxin's mechanism of action and
pharmacology, and we review its use in AML to date, focusing on details of
individual clinical trials. Most recently, when combined with cytarabine in a
randomized Phase III trial (VALOR), vosaroxin improved outcomes versus cytarabine
alone for relapsed/refractory AML in patients older than 60 years and for
patients in early relapse. We consider its continued role in the context of a
multifaceted strategy against AML, including its current use in clinical trials.
Prospective use will define its role in the evolving landscape of AML therapy.
PMID- 27615556
TI - Flexible Photodiodes Based on Nitride Core/Shell p-n Junction Nanowires.
AB - A flexible nitride p-n photodiode is demonstrated. The device consists of a
composite nanowire/polymer membrane transferred onto a flexible substrate. The
active element for light sensing is a vertical array of core/shell p-n junction
nanowires containing InGaN/GaN quantum wells grown by MOVPE. Electron/hole
generation and transport in core/shell nanowires are modeled within
nonequilibrium Green function formalism showing a good agreement with
experimental results. Fully flexible transparent contacts based on a silver
nanowire network are used for device fabrication, which allows bending the
detector to a few millimeter curvature radius without damage. The detector shows
a photoresponse at wavelengths shorter than 430 nm with a peak responsivity of
0.096 A/W at 370 nm under zero bias. The operation speed for a 0.3 * 0.3 cm2
detector patch was tested between 4 Hz and 2 kHz. The -3 dB cutoff was found to
be ~35 Hz, which is faster than the operation speed for typical photoconductive
detectors and which is compatible with UV monitoring applications.
PMID- 27615557
TI - Viral load is strongly associated with length of stay in adults hospitalised with
viral acute respiratory illness.
AB - BACKGROUND: Respiratory viruses are detectable in a large proportion of adults
hospitalised with acute respiratory illness. For influenza and other viruses
there is evidence that viral load and persistence are associated with certain
clinical outcomes but it is not known if there is an association between viral
load and hospital length of stay. METHODS: 306 adults hospitalised with viral
acute respiratory illness were studied. Associations between viral load and
length of stay were examined. Multiple linear regression analysis was performed
to control for age, comorbidity, influenza vaccine status, duration of illness
prior to hospitalisation, bacterial co-infection, clinical group and virus
subtype. RESULTS: High viral load was associated with a longer duration of
hospitalisation for all patients (p < 0.0001). This remained significant across
all virus types and clinical groups and when adjusted for age, comorbidity,
duration of illness prior to hospitalisation, bacterial co-infection and other
factors. CONCLUSIONS: High viral loads are associated with prolonged hospital
length of stay in adults with viral acute respiratory illness. This further
supports existing evidence demonstrating that viral acute respiratory illness is
a viral load driven process and suggests that viral load could be used in
clinical practise to predict prolonged hospitalisation and prioritise antivirals.
International Standard Randomised Controlled Trial Number (ISRCTN): 21521552.
PMID- 27615558
TI - Altered Mitochondrial Anatomy of Trigeminal Ganglia Neurons in Diabetes.
AB - Neurons from sensory ganglia are exposed to oxidative attack in diabetes. Altered
mitochondrial morphologies are due to impaired dynamics (fusion, fission) and to
cristae remodeling. This study aimed to evaluate using transmission electron
microscopy mitochondrial changes in diabetic trigeminal ganglia suggestive for
ignition of apoptosis, in absence of "classical" morphological signs of
apoptosis. We used samples of trigeminal ganglia (from six type 2 diabetes human
donors and five streptozotocin (STZ)-induced diabetic rats). In human diabetic
samples we found three main distributions of mitochondria: (a) small "dark"
normal mitochondria, seemingly resulted from fission processes; (b) small "dark"
damaged mitochondria, with side-vesiculations (single- and double-coated), large
matrix vesicles and cytosolic leakage of reactive species, mixed with larger
"light" mitochondria, swollen, and with crystolysis; (c) prevailing "light"
mitochondria. In STZ-treated rats a type (c) distribution prevailed, except for
nociceptive neurons where we found a different distribution: large and giant
mitochondria, suggestive for impaired mitochondrial fission, mitochondrial
fenestrations, matrix vesicles interconnected by lamellar cristae, and
mitochondrial leakage into the cytosol. Thus, the ultrastructural pattern of
mitochondria damage in diabetic samples of sensory neurons may provide clues on
the initiation of intrinsic apoptosis, even if the classical morphological signs
of apoptosis are not present. Further studies, combining use of biochemical and
ultrastructural techniques, may allow a better quantification of the degree in
which mitochondrial damage, with membrane alterations and cytosolic leaks, may be
used as morphological signs suggesting the point-of-no return for apoptosis. Anat
Rec, 299:1561-1570, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615559
TI - Comparison of dextran-based sirolimus-eluting stents and PLA-based sirolimus
eluting stents in vitro and in vivo.
AB - The aim of this study was to compare dextran and Poly(l-lactide) (PLLA) polymer
stent coatings as mediators for sirolimus (SRL) drug elution in a porcine
coronary model. The bare metal stent (BMS) surface was first coated with a layer
of SRL and then either dextran (DSS, a natural polymer) or PLA (PSS, a synthetic
polymer). The release velocity of SRL was slightly faster in DSS than PSS over
the first 7 days (78.5% and 62.3%, respectively, n = 10, p < 0.05) and continued
to 28 days in both groups. The contact angle was dramatically decreased in DSS
(38.7 degrees +/- 1.24) compared to BMS and PSS groups (72.7 degrees +/- 5.32
and 81.1o +/- 1.70, respectively, n = 10, p < 0.05). Smooth muscle cell migration
was arrested in both the DSS and PSS-treated groups compared to that in the
nontreated group (4.2% +/- 0.31, 5.8% +/- 0.60, 80.0% +/- 4.4, respectively, n =
10, p < 0.05). In the animal study, there were no significant differences in the
injury score, the internal elastic lamina, and the lumen area among the groups.
However, percent area stenosis was significantly decreased in the SRL-containing
group (27.5% +/- 2.52 in DSS and 27.9% +/- 3.30 in PSS) compared to BMS (35.9% +/
3.51, p < 0.05). The fibrin score was higher in the PSS (2.9 +/- 0.31) than BMS
(2.1 +/- 0.12) and DSS (2.5 +/- 0.66). The inflammation score in the DSS (0.7 +/-
0.21) was similar to that in the BMS (0.7 +/- 0.12), which was dramatically lower
than that PSS (1.5 +/- 0.18, p < 0.005). Immunofluorescence analysis revealed
that endothelialization was increased and inflammation prevented in the DSS.
These results suggest that dextran may be useful for the fabrication of drug
eluting stent as an alternative existing synthetic polymer. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 105A: 301-310, 2017.
PMID- 27615561
TI - High mass and spatial resolution mass spectrometry imaging of Nicolas Poussin
painting cross section by cluster TOF-SIMS.
AB - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using cluster
primary ion beams is used for the identification of the pigments in the painting
of Rebecca and Eliezer at the Well by Nicolas Poussin. The combination of the
high mass resolution of the technique with a sub-micrometer spatial resolution
offered by a delayed extraction of the secondary ions, together with the
possibility to simultaneously identifying both minerals and organics, has proved
to be the method of choice for the study of the stratigraphy of a paint cross
section. The chemical compositions of small grains are shown with the help of a
thorough processing of the data, with images of specific ions, mass spectra
extracted from small regions of interest, and profiles drawn along the different
painting layers. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27615560
TI - Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous
wound healing via optimizing the characteristics of fibroblasts.
AB - Prolonged healing and scar formation are two major challenges in the treatment of
soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role
in tissue regeneration, and recent studies have suggested that exosomes secreted
by stem cells may contribute to paracrine signaling. In this study, we
investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound
healing. We found that ASCs-Exos could be taken up and internalized by
fibroblasts to stimulate cell migration, proliferation and collagen synthesis in
a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1,
PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos
can be recruited to soft tissue wound area in a mouse skin incision model and
significantly accelerated cutaneous wound healing. Histological analysis showed
increased collagen I and III production by systemic administration of exosomes in
the early stage of wound healing, while in the late stage, exosomes might inhibit
collagen expression to reduce scar formation. Collectively, our findings indicate
that ASCs-Exos can facilitate cutaneous wound healing via optimizing the
characteristics of fibroblasts. Our results provide a new perspective and
therapeutic strategy for the use of ASCs-Exos in soft tissue repair.
PMID- 27615563
TI - Too much talk and not enough action over obesity plan.
AB - After all the build-up and delays, it was probably no surprise that the
government's eagerly-awaited childhood obesity plan has been derided for being
too timid. The 13-page document - relatively light considering the severity of
the posed threat - fails to mention tighter controls on advertising unhealthy
food and drinks to children and families. Without these controls it is hard to
see how the plan's stated aim of reducing childhood obesity in England over the
next ten years can be met.
PMID- 27615562
TI - Pathologic Intimal Thickening Plaque Phenotype: Not as Innocent as Previously
Thought. A Serial 3D Intravascular Ultrasound Virtual Histology Study.
AB - INTRODUCTION AND OBJECTIVES: Pathologic intimal thickening (PIT) has been
considered a benign plaque phenotype. We report plaque phenotypic changes in a
baseline/follow-up intravascular ultrasound-based virtual histology study.
METHODS: A total of 61 patients with stable coronary artery disease were analyzed
from the HEAVEN trial (89 patients randomized between routine statin therapy vs
atorvastatin 80mg and ezetimibe 10mg) with serial intravascular ultrasound
imaging of nonculprit vessels. We compared changes in 693 baseline and follow-up
5-mm long segments in a novel risk score, Liverpool Active Plaque Score (LAPS),
plaque parameters, and plaque composition. RESULTS: The PIT showed the highest
increase of risk score and, with fibrous plaque, also the LAPS. Necrotic core
(NC) abutting to the lumen increased in PIT (22 +/- 51.7; P = .0001) and in
fibrous plaque (17.9 +/- 42.6; P = .004) but decreased in thin cap fibroatheroma
(TCFA) (?15.14 +/- 52.2; P = .001). The PIT was the most likely of all nonthin
cap fibroatheroma plaque types to transform into TCFA at follow-up (11% of all
TCFA found during follow-up and 35.9% of newly-developed TCFA), but showed
(together with fibrous plaque) the lowest stability during lipid-lowering therapy
(24.7% of PIT remained PIT and 24.5% of fibrous plaque remained fibrous plaque).
CONCLUSIONS: Over the 1-year follow-up, PIT was the most dynamic of the plaque
phenotypes and was associated with an increase of risk score and LAPS (together
with fibrous plaque), NC percentage (together with fibrous plaque) and NC
abutting to the lumen, despite a small reduction of plaque volume during lipid
lowering therapy. The PIT was the main source for new TCFA segments.
PMID- 27615564
TI - Nurses must be prepared to talk to families about obesity.
AB - Nurses should be prepared to have difficult conversations with parents about diet
in a bid to tackle child obesity, the government has said.
PMID- 27615565
TI - Fewer school nurses puts children at risk.
AB - Falling numbers of school nurses are putting vulnerable children at risk, the RCN
has warned.
PMID- 27615566
TI - Dream come true for former 'sugar-bag baby'.
AB - A children's nursing student has returned to work on the same neonatal ward where
her life was saved when she was a baby.
PMID- 27615567
TI - Children with life-shortening conditions are denied the support they need, says
charity.
AB - Children who require palliative care are being 'short changed or ignored',
according to a survey of services in England by the charity Together for Short
Lives.
PMID- 27615568
TI - New group speaks for academics.
AB - A group has been launched to provide a strong and unified voice for academics
working in children and young people's nursing.
PMID- 27615570
TI - Efforts intensify to improve monitoring of sick children.
AB - There is compelling evidence that identifying and responding to deterioration in
patients is not as good as it should be.
PMID- 27615573
TI - Leading Change, Adding Value.
AB - Essential facts Leading Change, Adding Value is NHS England's new nursing and
midwifery framework. It is designed to build on Compassion in Practice (CiP),
which was published 3 years ago and set out the 6Cs: compassion, care,
commitment, courage, competence and communication. CiP established the values at
the heart of nursing and midwifery, while the new framework sets out how staff
can help transform the health and care sectors to meet the aims of the NHS
England's Five Year Forward View.
PMID- 27615574
TI - Active toddlers are less likely to grow obese.
AB - Keep toddlers toddling, and you will reduce the chance of them becoming obese in
the future. That is the conclusion of a survey of physical activity among pre
school children that relates exercise to body mass index (BMI) scores.
PMID- 27615575
TI - Management of type 1 diabetes in children is boosted by robots.
AB - A survey from the University of Liverpool concludes that young patients are
receptive to the use of humanoid robots, and that the younger the children are,
the more they are prepared to accept the advice of an assistant on castors.
PMID- 27615577
TI - Child health inequalities and 'wilful blindness'.
AB - This is a story of a divided semi-rural market town and how children and young
people were ignored. This is the story of how I helped children's voices to be
heard. It is a story of shame.
PMID- 27615579
TI - Nerves and excitement on my first placement.
AB - After working in the children's accident and emergency department as a healthcare
assistant for three years before starting university, I am about to start a
placement there as a nursing student.
PMID- 27615580
TI - Brittle bone disease.
AB - Brittle bone disease is also known as osteogenesis imperfecta, Vrolik syndrome
and Lobstein syndrome. The condition is not gender specific and is present in all
cultures. As the name of the disease suggests, the bones of people who have it
are brittle and prone to fracture.
PMID- 27615581
TI - How to prepare conference abstracts and poster presentations.
AB - An effective way of disseminating nursing research is to present it at a national
or international conference.
PMID- 27615582
TI - Co-ordinated and individualised transition planning for young people with complex
needs.
AB - Effective transition services can help young people with long-term conditions,
such as cerebral palsy, and learning disabilities to learn to practise self-care
and develop healthy behaviours. But transition is complicated if multiple
specialist services are required.
PMID- 27615583
TI - Improving transition for young people with cerebral palsy.
AB - Background Transitioning from child to adult healthcare services can be difficult
and distressing for families. The co-ordination and communication between
services needs to be improved.
PMID- 27615584
TI - Self-care of young people with long-term physical and mental health conditions.
AB - This article examines the evidence about 'what works' in supporting self-care in
relation to children or young people with physical and mental health conditions.
It is based on two systematic reviews and on research evaluating different self
care support programmes that have been developed in the UK. The authors identify
four components for an effective and acceptable self-care programme that nurses
can include when developing and providing such support for children and young
people with long-term physical and mental health conditions. These are: providing
a sense of community, developing knowledge and skills, building independence and
confidence, engaging children and young people. The authors highlight the
increasingly important role that children's and mental health nurses can play in
supporting young people's self-care.
PMID- 27615585
TI - Patients' experience of adolescent idiopathic scoliosis surgery: a
phenomenological analysis.
AB - Background Adolescent idiopathic scoliosis is a three-dimensional curvature of
the spine of unknown cause that occurs in often otherwise fit young people. A
complex surgical procedure is required for the most severe curves. Quantitative
literature suggests scoliosis surgery improves patients' lives, while qualitative
literature focuses on patients' concerns rather than their experience. Aims To
explore how adolescents interpret their perioperative experience. Method Six
participants, aged 15-18, were interviewed and transcripts were analysed.
Findings Four themes were identified: shock, fears and worries; parental
interaction; coping; and motivation and positivity. Conclusion Participants were
reluctant to share concerns, however those they shared related more to fear of
the unknown and lack of control than specific issues such as pain. Participants
depended on their parents, especially their mothers, during the perioperative
period, and they recognised their parents' stress. Participants coped well, were
motivated and had a positive outlook.
PMID- 27615586
TI - Undertaking safe medicine administration with children part 2: essential
numeracy.
AB - This is the second of two articles which aim to provide children's nurses with an
opportunity to develop their knowledge and skills of medicines management when
caring for children and young people. The first article considered the processes
associated with effective medicines management, including the concept of human
error. This article addresses essential numeracy and calculation skills that have
been identified as an important risk factor associated with medication errors in
children. The range of activities throughout the article will help you develop
and practise numeracy skills, with the answers for each activity at the end of
the article.
PMID- 27615587
TI - Inspired by children.
AB - What is your job? I act as an expert resource, supporting acute and community
teams to provide safe and timely transition home for children on long-term
ventilation (LTV) across London and the south east region. I provide parental and
professional education and training, and take part in patient involvement
projects, for example to ensure feedback is responded to. As a WellChild nurse I
link into the established WellChild nurses' national network, which helps me seek
support, share ideas and experiences with other nurses, contribute to research
and undertake study days.
PMID- 27615588
TI - How to engage in a reflective discussion for revalidation.
AB - How to engage in a reflective discussion for revalidation: 'The purpose of the
reflective discussion is to encourage a culture of information sharing,
reflection and improvement by enabling registrants to discuss their professional
development and improvement activities'.
PMID- 27615589
TI - Textbook coverage of holistic spiritual care.
AB - Nursing guidelines recommend that attention should be given to the spiritual and
religious needs of patients. This suggests that meeting the spiritual needs of
patients is an important aspect of holistic care, and that it should be
considered and supported wherever relevant.
PMID- 27615590
TI - Microcephaly and the Zika virus.
AB - Cases of microcephaly brought about by the Zika virus have brought professional
and personal challenges for nurses in Brazil. Paediatric nurses, such as Roberta
Seabra (pictured), take over as part of the multidisciplinary team once the baby
is born. In this article health writer Jacqui Thornton presents some personal
stories.
PMID- 27615591
TI - Legal and ethical issues in neonatal nursing.
AB - Neonatal nurses regularly face complex legal and ethical dilemmas. This article
discusses the hypothetical case of Jack, a two-day-old infant, born at 39 weeks'
gestation, and diagnosed with trisomy 13 (syndrome), a life-limiting condition
and being cared for in a neonatal intensive care unit. Jack's prognosis is poor
and he is not expected to live past two weeks of age.
PMID- 27615592
TI - Helping children with intellectual disabilities.
AB - There has been a move in children's services to encourage greater participation
by children themselves in how those services are designed and run. This is
equally important in services used by those who find it difficult to express
their views, yet children with complex needs appear to have less involvement in
their care than other groups.
PMID- 27615593
TI - Evaluation of in vivo estrogenic potency of natural estrogen-active chemical,
puerarin, on pituitary function in gonadectomized female rats.
AB - AIMS: Previous research has revealed that puerarin, the major phytoestrogen in
tuberous roots of Pueraria lobata and Pueraria mirifica, acts as a selective
estrogen receptor modulator that displays predominantly estrogenic potential for
health benefit. However, little is known about the estrogenic potency of puerarin
in pituitary, especially in the rat model of postmenopausal females. MAIN
METHODS: Plasma prolactin and growth hormone levels as well as mRNA expression
levels of pituitary estrogen-regulated genes, such as estrogen receptor (ER)
subtypes alpha (ERalpha) and beta (ERbeta), truncated ER product-1 (TERP-1) and
2 (TERP-2) and gonadotropin alpha subunit, were examined using radioimmunoassay
and TaqMan(r) real-time PCR, respectively. The effects were compared with the
potent ER agonist, 17beta-estradiol-3-benzoate (E2B), and both substances were
supplemented at low and high doses, i.e., 0.6 or 3g puerarin and 0.0043 or
0.0173g E2B per kilogram of phytoestrogens-free rat chow, and applied to
ovariectomized rats (five groups; 11-12 rats per group) for 12weeks. KEY
FINDINGS: Puerarin possessed weak E2B-like activities on pituitary function by
acting as ERbeta and TERP-1/-2 agonists, which resulted in the downregulation and
upregulation of ERbeta and TERP-1/-2 mRNA expressions, respectively, and
elevation of growth hormone levels. There were trends of decreased levels of
alpha subunit mRNA transcripts and increased levels of prolactin in puerarin
treated rats as observed in E2B-treated animals. SIGNIFICANCE: This is the first
report in ovariectomized rats the effects of puerarin on somatotropes and
pituitary estrogen-responsive mRNA expressions, which are very weakly estrogenic
by acting through ERbeta- and TERP-1/-2 mediated pathways.
PMID- 27615594
TI - Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel
and marketed cream.
AB - In the present study chitin nanogel loaded with anti-psoriatic drug clobetasol
was developed (CLCNG) for its topical delivery in psoriasis. CLCNG had the
particle size of 132+/-14nm, with gel like consistency, stability in
refrigerator, having higher drug release properties at acidic pH. CLCNG exhibited
significant toxicity towards HaCaT and THP-1cell lines by MTT assay. The uptake
of nanogel by HaCaT cell lines was confirmed by fluorescent microscopy. CLCNG at
0.35mg/ml exhibited significant anti-inflammatory activity with an average of 65%
and 70% inhibition in COX and LOX activities expressed in THP-1 cells. In vitro
skin permeation studies revealed the increased transdermal flux with fragmented
stratum corneum and loosened epidermal layers in CLCNG treated samples, compared
with control drug solution. The in vivo anti-psoriatic studies done on imiquimod
model confirmed the potential benefits of the nanogel for the topical delivery of
clobetasol in psoriasis.
PMID- 27615595
TI - Endothelial-mesenchymal transition in atherosclerotic lesion calcification.
AB - BACKGROUND AND AIMS: Endothelial-mesenchymal transitions (EndMTs) in endothelial
cells (ECs) contribute to vascular disease. METHODS: We used ApoE-/- mice fed a
high-fat/high-cholesterol diet. RESULTS: We reported evidence of EndMT in
atherosclerotic lesions contributing to calcification. Stem cell and mesenchymal
markers, including sex-determining region Y-box 2 (Sox2), were upregulated in
aortic ECs of fat-fed ApoE-/- mice. Limiting Sox2 decreased marker expression and
calcification in ApoE-/- aortas. Furthermore, a complex of serine proteases was
upregulated in ApoE-/- aortic ECs. Blockade of these proteases reduced expression
of Sox2 and atherosclerotic lesion calcification. CONCLUSIONS: Together, our data
suggest that EndMTs contribute to atherosclerotic lesion calcification.
PMID- 27615596
TI - Increased intermediate CD14++CD16++ monocyte subset levels associate with
restenosis after peripheral percutaneous transluminal angioplasty.
AB - BACKGROUND AND AIMS: We aimed at studying the association of three major human
monocyte subsets after percutaneous transluminal angioplasty (PTA) in patients
with femoropopliteal disease. METHODS: We prospectively studied 67 sequential
patients (40 male, 27 female; mean age 71 +/- 11 years) treated with
femoropopliteal angioplasty. Multi-color flow cytometry characterized monocyte
subsets from venous blood for expression of CD14 and CD16 and intracellular
myeloperoxidase (MPO) prior to, and 3, 6 and 12 months post PTA. Analyses tested
associations between monocyte subsets and risk for restenosis. RESULTS: 16/67
patients (24%) developed restenosis within 12 months after PTA. Patients with
hyperlipidemia had increased risk for restenosis (HR = 1.7, 95% CI 0.7-2.9, p =
0.001). Increased baseline monocytes associated with an increased risk of late
restenosis (HR = 4.9, 95% CI: 1.3-18.6, p = 0.047). CD14++CD16++ 'intermediate'
monocytes assessed at baseline, and after 3, 6, and 12 months significantly
associated with the risk for subsequent restenosis: HR = 3.9 (95% CI: 2.4-6.5, p
= 0.029), HR = 5.7 (95% CI = 0.7-44.7, p = 0.013), HR = 6.5 (95% CI: 2.5-16.9, p
= 0.001) and HR = 1.5 (95% CI = 1.4-15.5 p = 0.001), respectively. Moreover, the
probability for freedom of restenosis decreased with increased levels of
intermediate subsets at 12 months after PTA. Additionally, intracellular MPO
expression in CD14++CD16++ measured at 3, 6 and 12 months associated with an
increased restenosis risk (HR = 1.5, 95% CI: 0.8-2.1, p = 0.214, HR = 1.9, 95%
CI: 1.0-2.3 p = 0.051 and HR = 1.4, 95% CI: 1.0-1.8, p = 0.052). CONCLUSIONS: Our
results imply altered innate immunity after angioplasty. Elevated CD14++CD16++
intermediate monocyte frequencies and increased MPO expression may identify
individuals at heightened risk for restenosis.
PMID- 27615597
TI - Circulating angiotensin converting enzyme 2 activity as a biomarker of silent
atherosclerosis in patients with chronic kidney disease.
AB - BACKGROUND AND AIMS: Circulating Angiotensin Converting Enzyme 2 (ACE2) activity
in chronic kidney disease (CKD) patients without previous history of
cardiovascular disease (CVD) has been associated with classical risk factors
(older age, diabetes and male gender). Furthermore, silent atherosclerosis has
been described as a pathological link between CKD and CVD. We analyzed baseline
ACE2 activity in non-dialysis CKD stages 3-5 (CKD3-5) patients as a biomarker of
renal progression, silent atherosclerosis and CV events after 2 years of follow
up. METHODS: Prospective study of 1458 CKD3-5 subjects without any previous CV
event included in the Spanish multicenter NEFRONA study. Association between
baseline circulating ACE2 activity and renal parameters, carotid/femoral
echography, atheromatous disease, ankle-brachial index, intima-media thickness,
need of renal replacement therapy, cardiovascular events and mortality at 24
months of follow-up were analyzed. RESULTS: Patients with an increase in the
number of territories with plaques at 24 months showed significantly higher
levels of baseline ACE2 activity as compared to stable patients (29.6 (20.6
47.6)RFU/MUL/h versus 35.7 (24.5-56), p < 0.001). Multivariate linear regression
analysis showed that male gender, pathological ankle-brachial index and
progressive silent atherosclerosis defined as an increased number of territories
with plaques at 24 months were associated with increased baseline ACE2 activity.
Male gender, older age, diabetes, smoking and increased baseline circulating ACE2
were independent predictors of atherosclerosis at 24 months of follow-up.
CONCLUSIONS: In CKD3-5 patients, higher circulating ACE2 activity at baseline is
associated with higher risk for silent atherosclerosis, suggesting that ACE2 may
serve as a biomarker to predict CV risk before CVD is established.
PMID- 27615598
TI - Electrophysiologic features of fibular neuropathy in childhood and adolescence.
AB - INTRODUCTION: We studied patterns of nerve injury in pediatric common fibular
(peroneal) neuropathy (CFN). METHODS: A retrospective analysis was performed on
data from 53 children with CFN at a pediatric electromyography laboratory.
RESULTS: Conduction block at the fibular head was present in 35% of patients.
Deep fibular axonal loss was identified in 77%, while superficial fibular axonal
loss was identified in 45%. The pathophysiology was predominantly axonal in 72%,
mostly demyelinating in 6%, and mixed in 22%. Predominantly demyelinating lesions
at the fibular head demonstrated sparing of the superficial fibular sensory nerve
(P = 0.01, Fischer exact test). Predominantly axonal lesions had a moderate
correlation between superficial and deep fibular axonal loss (Spearman r = 0.52;
P = 0.0001). CONCLUSIONS: There is frequent axonal and fascicular injury in
pediatric CFN, similar to adults. Deep and superficial fibular nerve involvements
correlate in axonal lesions, whereas superficial fibular sensory fibers are often
spared in demyelinating lesions. Muscle Nerve, 2016 Muscle Nerve 55: 693-697,
2017.
PMID- 27615600
TI - PCR Quantification of D. folliculorum in Periocular Basal Cell Carcinoma.
PMID- 27615599
TI - Interactions between UCP2 SNPs and telomere length exist in the absence of
diabetes or pre-diabetes.
AB - Mitochondrial uncoupling protein 2 (UCP2) can affect oxidative stress levels.
UCP2 polymorphisms are associated with leukocyte telomere length (LTL) in Type 2
Diabetes, which also induces considerable background oxidative stress. The
effects of UCP2 polymorphisms on LTL in populations without diabetes have not
been well described. Our aims are to evaluate the interaction between LTL and
UCP2 polymorphisms in 950 subjects without diabetes. The monochrome multiplex
quantitative PCR method was used to measure relative LTL. Taqman SNP genotyping
assay was applied to genotypes for UCP2 rs659366 and rs660339. We found shorter
LTL associated with increased age (P < 0.001) and triglyceride levels (P =
0.041). After adjustment for cardiovascular risk factors, rs659336 GG genotype
carriers demonstrated a shorter LTL (1.257 +/- 0.186), compared to GA carriers
(1.288 +/- 0.230, P = 0.022) and AA carriers (1.314 +/- 0.253, P = 0.002). LTL
was shorter in the CC rs660339 genotype (1.254 +/- 0.187) compared to TT (1.297
+/- 0.242, P = 0.007) and CT carriers (1.292 +/- 0.229, P = 0.016). The T allele
of rs660339 is associated with a longer LTL of approximately 0.04 compared to CC
homozygotes. Thus, UCP2 rs659366 A allele and rs660339 T allele are both related
to longer LTL in subjects without diabetes, independent of cardiovascular risk
factors.
PMID- 27615601
TI - UK Age-Related Macular Degeneration Electronic Medical Record System (AMD EMR)
Users Group Report IV: Incidence of Blindness and Sight Impairment in Ranibizumab
Treated Patients.
AB - PURPOSE: To study the incidence of blindness and sight impairment in treatment
naive patients receiving ranibizumab (Lucentis) for neovascular age-related
macular degeneration (nAMD) in the United Kingdom (UK) National Health Service.
DESIGN: Multicenter nAMD database study. PARTICIPANTS: A total of 11 135 patients
who collectively received 92 976 treatment episodes to 12 951 eyes. METHODS: Data
were extracted from 14 UK centers using the same electronic medical record system
(EMR). The EMR-mandated collection of a data set (defined before first data
entry) including: age, Early Treatment Diabetic Retinopathy Study visual acuity
letter score (VA) for both eyes at all visits, and injection episodes.
Participating centers used overwhelmingly a pro re nata re-treatment posology at
intended monthly follow-up visits following a loading phase of 3 monthly
injections. MAIN OUTCOME MEASURES: Incidence of blindness and sight impairment
(VA in the better-seeing eye <38 letters [<=20/200 Snellen, approximately], and
<68 letters [<=20/50 Snellen, approximately] at 2 consecutive visits, or 1 visit
if no further follow-up data) in each year after initiating treatment. RESULTS:
Information from >300 000 clinic visits (2.8 million data points) collected over
5 years was collated from 14 centers. Mean age at first treatment was 79.7 years
(standard deviation = 9.19 years), with a female preponderance (63%). The mean
(median) VA at baseline in the better-seeing eye was 67.2 (72.0) letters, 20/40-
(20/40+) approximate Snellen conversion. The cumulative incidence of new
blindness and sight impairment in patients with treated nAMD in at least 1 eye at
years 1 to 4 after first injection were 5.1%, 8.6%, 12% and 15.6% for new
blindness and 29.6%, 41.0%, 48.7%, and 53.7% for new sight impairment, but with
significant reductions in the rates between year cohorts initiating treatment
(blindness [P = 4.72 * 10-08], sight impaired [P = 3.27 * 10-06]). CONCLUSIONS:
To the best of our knowledge, this is the first multicenter real-world study on
the incidence of blindness and sight impairment based on VA data in patients
treated with ranibizumab for nAMD, and its results show low incidences of both
blindness and sight impairment, which both declined during the study period.
PMID- 27615603
TI - Differential Cell Composition and Cytokine Expression Within Lymph Node
Granulomas from BCG-Vaccinated and Non-vaccinated Cattle Experimentally Infected
with Mycobacterium bovis.
AB - Cattle vaccination against bovine tuberculosis (bTB) has been proposed as a
supplementary method to help control the incidences of this disease. Bacillus
Calmette-Guerin (BCG) is currently the only viable candidate vaccine for
immunization of cattle against bTB, caused by Mycobacterium bovis (M. bovis). In
an attempt to characterize the differences in the immune response following M.
bovis infection between BCG-vaccinated and non-vaccinated animals, a combination
of gross pathology, histopathology and immunohistochemical (IHC) analyses was
used. BCG vaccination was found to significantly reduce the number of gross and
microscopic lesions present within the lungs and lymph nodes. Additionally, the
microscopically visible bacterial load of stages III and IV granulomas was
reduced. IHC using cell surface markers revealed the number of CD68+
(macrophages), CD3+ (T lymphocytes) and WC1+ cells (gammadelta T cells) to be
significantly reduced in lymph node granulomas of BCG-vaccinated animals, when
compared to non-vaccinated animals. B lymphocytes (CD79a+) were significantly
increased in BCG-vaccinated cattle for granulomas at stages II, III and IV. IHC
staining for iNOS showed a higher expression in granulomas from BCG-vaccinated
animals compared to non-vaccinated animals for all stages, being statistically
significant in stages I and IV. TGFbeta expression decreased alongside the
granuloma development in non-vaccinated animals, whereas BCG-vaccinated animals
showed a slight increase alongside lesion progression. IHC analysis of the
cytokines IFN-gamma and TNF-alpha demonstrated significantly increased expression
within the lymph node granulomas of BCG-vaccinated cattle. This is suggestive of
a protective role for IFN-gamma and TNF-alpha in response to M. bovis infection.
Findings shown in this study suggest that the use of BCG vaccine can reduce the
number and severity of lesions, induce a different phenotypic response and
increase the local expression of key cytokines related to protection.
PMID- 27615602
TI - Factors associated with significant liver necroinflammation in chronic hepatitis
B patients with cirrhosis.
AB - We determined the association between various clinical parameters and significant
liver necroinflammation in patients with chronic hepatitis B (CHB) related
cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the
final analysis. Clinical laboratory values and characteristics were obtained from
the medical record. We performed analyses of the relationships between
independent variables and significant liver necroinflammation by using binary
logistic regression analysis and discriminant analysis. Significant liver
necroinflammation (grade>=2) was found in 58.0% (80/138) of antiviral therapy
patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also,
there were some significant differences in serum hepatitis B surface antigen
(HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV)
DNA between antiviral therapy and non antiviral therapy patients. After that,
aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA),
prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI)
and serum HBV DNA were confirmed as independent predictors of significant liver
necroinflammation in CHB patients with cirrhosis by univariate analysis and
multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02
respectively). Finally, receiver operating characteristic (ROC) curve analysis
and discriminant analysis validated that these six variables together have strong
predictive power to evaluate significant liver necroinflammation.
PMID- 27615604
TI - miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200.
AB - Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes
of morbidity and mortality in women. Persistent High-risk human papillomavirus
(hrHPV) infection is closely related to cervical cancer and autophagy has been
suggested to inhibit viral infections. miRNAs have been reported to regulate
autophagy in many solid tumors with many studies implicating miR-224-3p in the
regulation of autophagy. In this study, we performed a miRNA microarray analysis
on CC tissues and found that a large number of miRNAs with differential
expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate
miRNA selectively up regulated in HPV-infected tissues and cell lines. Further
analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues
and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV
infected cells, knocking down endogenous miR-224-3p increases autophagy activity
in the same cells. In addition, we found that miR-224-3p directly inhibits the
expression of autophagy related gene, FAK family-interacting protein of 200 kDa
(FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV
induced cervical cancer cells through targeting FIP200 expression.
PMID- 27615606
TI - Organization of Non-centrosomal Microtubules in Epithelial Cells.
AB - Polarized epithelial cells contain a characteristic array of microtubules in
which non-centrosomal microtubules are aligned along the apical-to-basal axis of
the cell with their minus ends oriented towards the apical pole. Although this
unique orientation of microtubules was discovered in the late 1980s, how this
orientation is established remains unresolved partly because of limited
information about molecular factors that regulate the minus ends of non
centrosomal microtubules. Recent studies, however, identified novel minus end
associated proteins, revealing mechanisms by which the polarized arrays of
microtubules are established in epithelial cells. These studies have also
demonstrated the importance of apico-basally orientated microtubules in intra
structural organization of cells. This review focuses on recent progress of our
understanding of the molecular basis for epithelium-specific microtubule assembly
and function.
PMID- 27615605
TI - Optimal search patterns in honeybee orientation flights are robust against
emerging infectious diseases.
AB - Levy flights are scale-free (fractal) search patterns found in a wide range of
animals. They can be an advantageous strategy promoting high encounter rates with
rare cues that may indicate prey items, mating partners or navigational
landmarks. The robustness of this behavioural strategy to ubiquitous threats to
animal performance, such as pathogens, remains poorly understood. Using honeybees
radar-tracked during their orientation flights in a novel landscape, we assess
for the first time how two emerging infectious diseases (Nosema sp. and the
Varroa-associated Deformed wing virus (DWV)) affect bees' behavioural performance
and search strategy. Nosema infection, unlike DWV, affected the spatial scale of
orientation flights, causing significantly shorter and more compact flights.
However, in stark contrast to disease-dependent temporal fractals, we find the
same prevalence of optimal Levy flight characteristics (MU ~ 2) in both healthy
and infected bees. We discuss the ecological and evolutionary implications of
these surprising insights, arguing that Levy search patterns are an emergent
property of fundamental characteristics of neuronal and sensory components of the
decision-making process, making them robust against diverse physiological effects
of pathogen infection and possibly other stressors.
PMID- 27615607
TI - Cataract Surgery Complications and Revisit Rates Among Three States.
AB - PURPOSE: To characterize population-based 30-day procedure-related readmissions
(revisits) following cataract surgery. SETTING: Ambulatory cataract surgery
performed in California, Florida, or New York. DESIGN: Retrospective cohort
study. METHODS: This study used all-capture state administrative datasets.
Cataract procedures from California, Florida, and New York state ambulatory
surgery settings were identified using ICD-9-CM and CPT codes. Thirty-day
readmissions (revisits) were identified in inpatient, ambulatory, and emergency
department settings across each state. RESULTS: Across the 3 states, the all
cause 30-day readmission rate was 6.0% and the procedure-related readmission
(revisit) rate was 1.0%. Procedure-related revisits were highest for patients
aged 20-29 (2.9%) and 30-39 (2.3%) and lowest for patients aged 70-79 (0.9%).
Multivariate associations between clinical characteristics and 30-day procedure
related revisits included age 20-29 (odds ratio [OR]: 3.13; 95% confidence
intervals [CI]: 2.33-4.20) and age 30-39 (OR: 2.35; CI: 1.91-2.89) compared with
age 70-79, male sex (OR: 1.29; CI: 1.24-1.34), races black (OR: 1.37; CI: 1.27
1.48) and Hispanic (OR: 1.16; CI: 1.08-1.24) compared with white, and Medicaid
insurance (OR: 1.18, CI: 1.07-1.30) compared with Medicare. Diabetes was also
associated with increased 30-day procedure-related revisits (OR: 1.093, CI: 1.024
1.168). CONCLUSIONS: Cataract surgery is a common and, in aggregate, expensive
procedure. Complication-related revisits follow a similar trend as surgical
complications in large-scale population data, and may be useful as a preliminary,
screening outcome measure. Our results highlight the importance of age as a risk
factor for cataract surgery readmissions, and suggest a relationship between
black or Hispanic race, Medicaid insurance, and diabetes associated with higher
risk for cataract surgery complications.
PMID- 27615608
TI - Isotope geochemistry reveals ontogeny of dispersal and exchange between main
river and tributary habitats in smallmouth bass Micropterus dolomieu.
AB - Radiogenic strontium isotope ratios (87 Sr:86 Sr) in otoliths were compared with
isotope ratios predicted from models and observed in water sampling to
reconstruct the movement histories of smallmouth bass Micropterus dolomieu
between main-river and adjacent tributary habitats. A mechanistic model
incorporating isotope geochemistry, weathering processes and basin accumulation
reasonably predicted observed river 87 Sr:86 Sr across the study area and
provided the foundations for experimental design and inferring fish provenance.
Exchange between rivers occurred frequently, with nearly half (48%) of the 209
individuals displaying changes in otolith 87 Sr:86 Sr reflecting movement between
isotopically distinct rivers. The majority of between-river movements occurred in
the first year and often within the first few months of life. Although more
individuals were observed moving from the main river into tributaries, this
pattern did not necessarily reflect asymmetry in exchange. Several individuals
made multiple movements between rivers over their lifetimes; no patterns were
found, however, that suggest seasonal or migratory movement. The main-river sport
fishery is strongly supported by recruitment from tributary spawning, as 26% of
stock size individuals in the main river were spawned in tributaries. The
prevailing pattern of early juvenile dispersal documented in this study has not
been observed previously for this species and suggests that the process of
establishing seasonal home-range areas occurs up to 2 years earlier than
originally hypothesized. Extensive exchange between rivers would have substantial
implications for management of M. dolomieu populations in river-tributary
networks.
PMID- 27615609
TI - Interleukin-1alpha induces focal degradation of biglycan and tissue degeneration
in an in-vitro ovine meniscal model.
AB - We have developed an ovine meniscal explant model where the focal degradative
events leading to characteristic fragmentation patterns of biglycan in human OA
of the knee and hip, and evident in animal models of knee OA and IVD degeneration
are reproduced in culture. Lateral and medial menisci were dissected into outer,
mid and inner zones and established in explant culture+/-IL-1 (10ng/ml). The
biglycan species present in conditioned media samples and in GuHCl extracts of
tissues were examined by Western blotting using two C-terminal antibodies PR-85
and EF-Bgn. Clear differences were evident in the biglycan species in each
meniscal tissue zone with the medial outer meniscus having lower biglycan levels
and major fragments of 20, 28, 33 and 36, 39kDa. Similar fragmentation was
detected in articular cartilage samples, 42-45kDa core protein species were also
detected. Biglycan fragmentation was not as extensive in the IL-1 stimulated
meniscal cultures with 36, 39, 42 and 45kDa biglycan species evident. Thus the
medial meniscus outer zone displayed the highest levels of biglycan processing in
this model and correlated with a major zone of meniscal remodelling in OA in man.
Significantly, enzymatic digests of meniscal tissues with MMP-13, ADAMTS-4 and
ADAMTS-5 have also generated similar biglycan species in-vitro. Zymography
confirmed that the medial outer zone was the region of maximal MMP activity. This
model represents a convenient system to recapitulate matrix remodelling events
driven by IL-1 in pathological cartilages and in animal models of joint
degeneration.
PMID- 27615665
TI - Inspiratory modulation of sympathetic activity is increased in female rats
exposed to chronic intermittent hypoxia.
AB - NEW FINDINGS: What is the central question of the study? There are sex
differences in the respiratory network and in the regulation of arterial blood
pressure. Female rats develop hypertension after chronic intermittent hypoxia
(CIH). In this context, we evaluated the respiratory-related mechanism underlying
the development of hypertension in CIH-exposed female rats. What is the main
finding and its importance? Female rats exposed to CIH develop changes in the
respiratory pattern related to inspiration and sympathetic overactivity phase
locked to the inspiratory phase of the respiratory cycle, which is different from
CIH-exposed male rats. These data suggest a specific respiratory mechanism for
sympathetic overactivity in hypertensive CIH-exposed female rats. Chronic
intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in
male rats. Enhanced respiratory modulation of sympathetic activity in juvenile
male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle,
characterizing changes in respiratory-sympathetic coupling. Different from other
experimental models of hypertension, CIH induces an increase in arterial pressure
in adult female rats similar to that observed in male rats. However, the
mechanisms underlying the hypertensive phenotype in CIH-exposed female rats
remain to be elucidated. Moreover, several lines of evidence have documented sex
differences in respiratory network activity in response to hypoxia. Considering
that CIH-exposed male rats present an increase in the respiratory modulation of
sympathetic activity and there are sex differences in the respiratory network, we
hypothesized that CIH-exposed female rats develop an increase in the respiratory
modulation of sympathetic activity different from CIH-exposed male rats. In this
study, we investigated sympathetic and respiratory activities in juvenile female
rats exposed to CIH using an in situ working heart-brainstem preparation. The CIH
exposed female rats developed changes in the respiratory pattern and changes in
the respiratory-sympathetic coupling marked by sympathetic overactivity phase
locked to inspiration, which was different from male rats exposed to CIH. This
study revealed a specific respiratory-related mechanism for sympathetic
overactivity linked to inspiration that explains, at least in part, the
hypertensive phenotype in female rats exposed to CIH.
PMID- 27615666
TI - Association of neutrophil-lymphocyte ratio with metabolic syndrome and its
components in Asian Indians (CURES-143).
AB - BACKGROUND: Metabolic syndrome (MS) is the state of chronic low grade
inflammation. This study looks at the relationship of neutrophil-lymphocyte ratio
(NLR) in subjects with and without MS in Asian Indians. METHODS: Study subjects
(n=754) were recruited from the Chennai Urban Rural Epidemiology Study. MS was
defined using the National Cholesterol Education Program-Adult Treatment Panel
(NCEP-ATP) III criteria modified for waist according to World Health Organization
Asia Pacific guidelines. A complete hemogram was done in all subjects using a
five-part hematology analyzer (model SF-3000; Sysmex, Kobe, Japan). The NLR was
calculated as the ratio between counts for neutrophils and total lymphocytes in
subjects with (n=422) and without (n332) MS and correlated with number of
metabolic abnormalities in those with MS. RESULTS: Subjects with five metabolic
abnormalities had the highest NLR, and with decreasing number of metabolic
abnormalities, the NLR decreased linearly (p for trend <0.001). Logistic
regression analysis revealed that even after adjusting for age, gender and body
mass index, MS was strongly associated with NLR (p<0.001). CONCLUSION: Among
Asian Indians, NLR is correlated with MS and also with the number of metabolic
abnormalities.
PMID- 27615668
TI - Decentralized finite-time attitude synchronization for multiple rigid spacecraft
via a novel disturbance observer.
AB - This paper investigates decentralized finite-time attitude synchronization for a
group of rigid spacecraft by using quaternion with the consideration of
environmental disturbances, inertia uncertainties and actuator saturation.
Nonsingular terminal sliding mode (TSM) is used for controller design. Firstly, a
theorem is proven that there always exists a kind of TSM that converges faster
than fast terminal sliding mode (FTSM) for quaternion-descripted attitude control
system. Controller with this kind of TSM has faster convergence and reduced
computation than FTSM controller. Then, combining with an adaptive parameter
estimation strategy, a novel terminal sliding mode disturbance observer is
proposed. The proposed disturbance observer needs no upper bound information of
the lumped uncertainties or their derivatives. On the basis of undirected
topology and the disturbance observer, decentralized attitude synchronization
control laws are designed and all attitude errors are ensured to converge to
small regions in finite time. As for actuator saturation problem, an auxiliary
variable is introduced and accommodated by the disturbance observer. Finally,
simulation results are given and the effectiveness of the proposed control scheme
is testified.
PMID- 27615669
TI - Enthalpy-Entropy Compensation Effect in Chemical Kinetics and Experimental
Errors: A Numerical Simulation Approach.
AB - Many kinetic studies concerning homologous reaction series report the existence
of an activation enthalpy-entropy linear correlation (compensation plot), its
slope being the temperature at which all the members of the series have the same
rate constant (isokinetic temperature). Unfortunately, it has been demonstrated
by statistical methods that the experimental errors associated with the
activation enthalpy and entropy are mutually interdependent. Therefore, the
possibility that some of those correlations might be caused by accidental errors
has been explored by numerical simulations. As a result of this study, a computer
program has been developed to evaluate the probability that experimental errors
might lead to a linear compensation plot parting from an initial randomly
scattered set of activation parameters (p-test). Application of this program to
kinetic data for 100 homologous reaction series extracted from bibliographic
sources has allowed concluding that most of the reported compensation plots can
hardly be explained by the accumulation of experimental errors, thus requiring
the existence of a previously existing, physically meaningful correlation.
PMID- 27615667
TI - Adiposity is inversely associated with hippocampal volume in African Americans
and European Americans with diabetes.
AB - AIMS: To assess associations between body mass index (BMI), waist circumference
(WC), and computed tomography-determined volumes of pericardial, visceral, and
subcutaneous adipose tissue with magnetic resonance imaging-(MRI) based cerebral
structure and cognitive performance in individuals with type 2 diabetes (T2D).
METHODS: This study was performed in 348 African Americans (AAs) and 256 European
Americans (EAs) with T2D. Associations between adiposity measures with cerebral
volumes of white matter (WMV), gray matter (GMV), white matter lesions,
hippocampal GMV, and hippocampal WMV, cognitive performance and depression were
examined using marginal models incorporating generalized estimating equations.
All models were adjusted for age, sex, education, smoking, HbA1c, hypertension,
statins, cardiovascular disease, MRI scanner (MRI outcomes only), and time
between scans; some neuroimaging measures were additionally adjusted for
intracranial volume. RESULTS: Participants were 59.9% female with mean (SD) age
57.7(9.3)years, diabetes duration 9.6(6.8)years, and HbA1c 7.8(1.9)%. In AAs,
inverse associations were detected between hippocampal GMV and both BMI (beta
[95% CI]-0.18 [-0.30, -0.07], P=0.0018) and WC (-0.23 [-0.35, -0.12], P=0.0001).
In the full bi-ethnic sample, inverse associations were detected between
hippocampal WMV and WC (P<=0.0001). Positive relationships were observed between
BMI (P=0.0007) and WC (P<0.0001) with depression in EAs. CONCLUSIONS: In patients
with T2D, adiposity is inversely associated with hippocampal gray and white
matter volumes.
PMID- 27615670
TI - Novel mobbing strategies of a fish population against a sessile annelid predator.
AB - When searching for food, foraging fishes expose themselves to hidden predators.
The strategies that maximize the survival of foraging fishes are not well
understood. Here, we describe a novel type of mobbing behaviour displayed by
foraging Scolopsis affinis. The fish direct sharp water jets towards the hidden
sessile annelid predator Eunice aphroditois (Bobbit worm). We recognized two
different behavioural roles for mobbers (i.e., initiator and subsequent
participants). The first individual to exhibit behaviour indicating the discovery
of the Bobbit directed, absolutely and per time unit, more water jets than the
subsequent individuals that joined the mobbing. We found evidence that the
mobbing impacted the behaviour of the Bobbit, e.g., by inducing retraction. S.
affinis individuals either mob alone or form mobbing groups. We speculate that
this behaviour may provide social benefits for its conspecifics by securing
foraging territories for S. affinis. Our results reveal a sophisticated and
complex behavioural strategy to protect against a hidden predator.
PMID- 27615671
TI - Erratum to "Re: Woolsey T.A., van der Loos H. 1970. The structural organization
of layer IV in the somatosensory region (S I) of mouse cerebral cortex" [Brain
Res. 17 (1970) 205-242].
PMID- 27615672
TI - The influence of sulfur configuration in 1 H NMR chemical shifts of diasteromeric
five-membered cyclic sulfites.
AB - The effect of the stereochemistry of the sulfur atom on 1 H chemical shifts of
the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5
phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete 1 H and 13 C NMR
spectral assignment was achieved by the use of one-dimensional and two
dimensional NMR techniques in combination with X-ray data. A correlation of
experimental data with theoretical calculations of chemical shift tensors using
density functional theory and topological theory of atoms in molecules was made.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27615673
TI - Survey of the Variation in Grape Marc Condensed Tannin Composition and
Concentration and Analysis of Key Compositional Factors.
AB - Grape marc contains a number of compounds with potential antimethanogenic
activity in ruminants, including condensed tannins (CTs). Using direct
phloroglucinolysis, a survey of CT chemistry across 66 grape marc samples showed
diversity in concentration (6.9 to 138.8 g/kg of dry matter). Concentration was
found to be independent of CT composition, although all compositional variables
were significantly correlated (P < 0.0001). Twenty samples diverse in CT were
selected from a cluster analysis and analyzed for compounds relevant to ruminant
digestion and methanogenesis, including metabolizable energy (6.6-12.0 MJ/kg DM),
crude protein (3.2-14.4% DM), neutral detergent fiber (18.4-61.4% DM), and
ethanol soluble carbohydrates (2.0-40.6% DM). Fatty acid concentrations varied
throughout the 20 samples (5.2-184.5 g/kg DM), although fatty acid profile showed
two distinct groups. Grape marc varies widely in nutritional value, and in
compounds that have been linked with changes in ruminant digestion and methane
emissions.
PMID- 27615674
TI - Psychiatric disorders among women with the fragile X premutation without children
affected by fragile X syndrome.
AB - Several studies have demonstrated increased rates of anxiety and depressive
disorders among female carriers of the fragile X premutation. However, the
majority of these studies focused on mothers of children with fragile X syndrome,
who experience higher rates of parenting stress that may contribute to the
emergence of these disorders. The present study compared psychiatric symptom
presentation (utilizing measures of current symptoms and lifetime DSM-IV Axis I
disorders) in 24 female carriers without affected children (mean age = 32.1
years) to 26 non-carrier women from the community (mean age = 30.5 years). We
also examined the association between CGG repeat size (adjusted for X activation
ratio) and mRNA, with severity of psychiatric symptoms. Women with the
premutation reported significantly elevated symptoms of anxiety, depression,
interpersonal sensitivity, obsessive-compulsiveness, and somatization relative to
controls during the past week. Carriers had significantly higher rates of
lifetime social phobia (42.3%) compared to controls (12.5%); however, this
comparison did not remain significant after multiple comparison adjustment. Rates
of other psychiatric disorders were not significantly elevated relative to
controls, though it should be noted that lifetime rates among controls were much
higher than previously published population estimates. Although the sample is
relatively small, the study of this unique cohort suggests the premutation
confers risk for mood and anxiety disorders independent of the stress of
parenting children with FXS. Screening for psychiatric disorders in women with
the premutation, even before they become parents, is important and highly
encouraged. (c) 2016 Wiley Periodicals, Inc.
PMID- 27615675
TI - Effects of naloxone on motion sickness in cats alone and with broad spectrum
antiemetics.
AB - Doses of naloxone far below those which elicit emesis increase the sensitivity to
motion sickness. In order to evaluate the possible interaction with broad
spectrum antiemetics, low doses of naloxone were tested alone and in combination
with 8-hydroxy-2-(di-n-propylamine)tetralin (DPAT), fentanyl and the NK1
antagonist CP-99994. A modified autonomic symptom rating scale was unaffected by
any drug and thus considered of little value. Fentanyl and NK1 antagonists
decreased the duration of the retch/vomit sequence. Naloxone alone and in
combination with each of the drugs increased the duration of retching/vomiting.
Naloxone also increased the number of vomiting sequences. The results are
interpreted in terms of possible site(s) of action of the antiemetic drugs.
PMID- 27615676
TI - Whither the impending european regulation of presumed endocrine disruptors?
PMID- 27615677
TI - Ultralight Biomass-Derived Carbonaceous Nanofibrous Aerogels with Superelasticity
and High Pressure-Sensitivity.
AB - Superelastic and pressure-sensitive carbonaceous nanofibrous aerogels with a
honeycomb-like structure are fabricated through the combination of sustainable
konjac glucomannan biomass and flexible SiO2 nanofibers. The aerogels can detect
dynamic pressure with a wide pressure range and high sensitivity, which enables
real pressure signals, such as human blood pulses, to be monitored in real time
and in situ.
PMID- 27615678
TI - Computational modeling and molecular dynamics simulations of mammalian
cytoplasmic tyrosyl-tRNA synthetase and its complexes with substrates.
AB - Cytoplasmic tyrosyl-tRNA synthetase (TyrRS) is one of the key enzymes of protein
biosynthesis. TyrRSs of pathogenic organisms have gained attention as potential
targets for drug development. Identifying structural differences between various
TyrRSs will facilitate the development of specific inhibitors for the TyrRSs of
pathogenic organisms. However, there is a deficiency in structural data for
mammalian cytoplasmic TyrRS in complexes with substrates. In this work, we
constructed spatial structure of full-length Bos taurus TyrRS (BtTyrRS) and its
complexes with substrates using the set of computational modeling techniques.
Special attention was paid to BtTyrRS complexes with substrates [L-tyrosine, K+
and ATP:Mg2+] and intermediate products [tyrosyl-adenylate (Tyr-AMP), K+ and
PPi:Mg2+] with the different catalytic loop conformations. In order to analyze
their dynamical properties, we performed 100 ns of molecular dynamics (MD)
simulations. MD simulations revealed new structural data concerning the tyrosine
activation reaction in mammalian TyrRS. Formation of strong interaction between
Lys154 and gamma-phosphate suggests the additional role of CP1 insertion as an
important factor for ATP binding. The presence of a potassium-binding pocket
within the active site of mammalian TyrRS compensates the absence of the second
lysine in the KMSKS motif. Our data provide new details concerning a role of K+
ions at different stages of the first step of the tyrosylation reaction,
including the coordination of substrates and involvement in the PPi releasing.
The results of this work suggest that differences between ATP-binding sites of
mammalian and bacterial TyrRSs are meaningful and could be exploited in the drug
design.
PMID- 27615680
TI - The genus Pholetesor Mason, 1981 (Hymenoptera, Braconidae, Microgastrinae) from
China, with descriptions of eleven new species.
AB - The genus Pholetesor Mason from China is revised. Eleven new species are
described and illustrated, namely P. acricauda Liu & Chen, sp. n., P.
argyresthiae Liu & Chen, sp. n., P. artusisulcus Liu & Chen, sp. n., P. confusus
Liu & Chen, sp. n., P. flavigleba Liu & Chen, sp. n., P. flaviparvus Liu & Chen,
sp. n., P. lithocolletis Liu & Chen, sp. n., P. lyonetiae Liu & Chen, sp. n., P.
spinadensus Liu & Chen, sp. n., P. taiwanensis Liu & Chen, sp. n., and P.
teresitergum Liu & Chen, sp. n. Six species are newly recorded in China, namely
P. arisba (Nixon, 1973), P. circumscriptus (Nees, 1834), P. laetus (Marshall,
1885), P. maritimus (Wilkinson, 1941), P. salalicus Mason, 1959 and P.
viminetorum (Wesmael, 1837). A key to the Chinese species of this genus is
provided.
PMID- 27615679
TI - Coincidence of PTPN22 c.1858CC and FCRL3 -169CC genotypes as a biomarker of
preserved residual beta-cell function in children with type 1 diabetes.
AB - BACKGROUND: Genotype-phenotype studies in type 1 diabetes (T1DM) patients are
needed for further development of therapy strategies. OBJECTIVE: Our aims were to
investigate the distribution of selected PTPN22 and FCRL3 gene polymorphisms and
their associations with clinical course of disease in children with newly
diagnosed T1DM from the Pomeranian region of Poland. SUBJECTS/METHODS: The
prospective, longitudinal study of 147 children with newly diagnosed T1DM
autoimmune subtype was conducted. The PTPN22 c.1858T>C (rs2476601) and FCRL3
169C>T (rs7528684) polymorphisms were analyzed using polymerase chain reaction
restriction fragment length polymorphism method (PCR-RFLP) and DNA sequencing.
The frequencies of genotypes were compared between the study and population
matched control group (327 random anonymous samples from the Pomeranian region).
Selected patients underwent a 24-monthly follow up [periodic re-evaluation of
fasting C-peptide concentration (FCP) and hemoglobin A1c (HbA1c ) level].
RESULTS: A significantly lower coincidence of the PTPN22 c.1858CC and FCRL3
169CC genotypes was found in the study group compared with controls (P = 0.04).
The PTPN22 c.1858CC and FCRL3 -169CC genotype combination, restricted to female
patients only, was associated with well-preserved residual beta-cell function
throughout the entire follow up (prolonged FCP level increase up to the sixth
month of disease, with further very stable dynamics-FCP median level >=0.67 ng/mL
without significant decrease up to the 24th month). HbA1c levels in this subgroup
also remained the lowest during the observation period.
CONCLUSIONS/INTERPRETATION: Ascertained phenomenon could be explained by an
interacting mechanism of the two polymorphisms through estrogen-regulated nuclear
factor kappa B signaling in regulatory T (Treg ) lymphocytes. This hypothesis, if
confirmed, may lead to further development of Treg administration-based
therapies.
PMID- 27615681
TI - A new species of Lepidocyrtus (Collembola, Entomobryidae) from the Borzsony
Mountains, Hungary.
AB - The genus Lepidocyrtus was previously represented by 17 species in Hungary,
including four species with locus typicus in this country. Opportunistic sampling
in mid-mountain grassland and forest habitats resulted in records of several
species from the L. lignorum group and allowed to describe the new species L.
traseri sp. nov. The L. lignorum group, established and named after the eponymic
species, is composed by a total of 11 species. The main characteristics shared by
every species in this group are the dorsal body macrochaetotaxy
R0R1R2/00/0101+3 and the presence of scales on
the antennae and legs. The new species is close to L. lignorum (Fabricius, 1793)
and L. violaceus (Geoffroy, 1762) but differs from them by the color pattern,
number of interocular scales, type of labral papillae and the number of inner
setae on the manubrial plate. An identification key is given for differentiating
all species of this group.
PMID- 27615682
TI - New Black Fungus Gnats (Diptera, Sciaridae) of North America Part I. Genus
Scatopsciara Edwards, 1927.
AB - In the Nearctic region the genus Scatopsciara includes 37 species. Herein these
species are diagnosed, keyed and distribution data provided. Twenty six species
are known exclusively from the Nearctic region. Eleven species have a Holarctic
distribution. Nineteen species are described as new for science. These are:
Scatopsciara abedabunae sp. n. (USA, Canada), Sc. adsilae sp. n. (USA), Sc.
alawae sp. n. (USA), Sc. awanatae sp. n. (USA), Sc. awinitae sp. n. (USA,
Canada), Sc. catoriae sp. n. (USA), Sc. chenoae sp. n. (USA), Sc. inesae sp. n.
(USA), Sc. itumae sp. n. (USA), Sc. miakodae sp. n. (USA), Sc. praealawae sp. n.
(USA), Sc. praeawanatae sp. n. (USA), Sc. subawanatae sp. n. (USA), Sc.
subdendrotica sp. n. (Canada), Sc. subfratercula sp. n. (Canada), Sc. subgrossa
(USA), Sc. subitumae sp. n. (USA), Sc. submiakodae sp. n. (USA) and Sc.
tricuspidatula sp. n. (USA). The following five species are new for North
America: Scatopsciara curviforceps Bukowski & Lengersdorf, 1936, Sc. geophila
Tuomikoski, 1960, Sc. neglecta Menzel & Mohrig 1998, Sc. subciliata Tuomikoski,
1960 and Sc. ventrospinula Mohrig & Mamaev, 1983. Six species, included in
Corynoptera so far were transferred to the genus Scatopsciara. These are Sc.
armigera (Vilkamaa & Hippa, 2006), Sc. fratercula (Vilkamaa & Hippa, 2006), Sc.
robustior (Vilkamaa & Hippa, 2006), Sc. vagula (Tuomikoski, 1960), Sc. fera
(Mohrig & Heller, 1992) (in Heller & Mohrig, 1992) and Sc. nyxa (Mohrig & Menzel,
1992).
PMID- 27615683
TI - Checklist and analysis of completeness of the reef fish fauna of the
Revillagigedo Archipelago, Mexico.
AB - This paper presents an updated checklist of cartilaginous and bony fishes from
the Revillagigedo Archipelago reefs and nearby areas (Tropical Eastern Pacific).
To compile this list, we gathered data from field surveys between 1994 and 2015,
from an exhaustive literature review, and by consulting museum collections and
databases. With these records we estimated the completeness of the local fish
inventory using four non-parametric rarefaction methods. We report a total of 389
species in 102 families; 235 of these are reef fish that occur in the Eastern but
also in the Central Pacific, and 13 species were identified as endemic to the
archipelago. A non-parametric statistical model predicts that the expected number
of reef fish present at Revillagigedo should be 244.3 +/- 3.2 species, which is 9
species more than the observed richness, and this difference was statistically
significant (p = 0.02). That predictive model estimates that about 96% of the
total richness of reef fish from the archipelago is known. Comparisons of the
completeness of the inventory at Revillagigedo to that reported for the fish
fauna of the Eastern Pacific and worldwide, showed that the quality of the
sampling effort is remarkably high, in spite of the geographic isolation of the
archipelago.
PMID- 27615684
TI - Two new paratanaid Tanaidacea (Crustacea: Malacostraca: Peracarida) from the
Hawaiian Islands, with illustrated taxonomic keys.
AB - Two new tanaidomorphan tanaidaceans, Aparatanais hawaiensis, sp. nov. and
Metatanais spinipropodus, sp. nov. represent the first members of the Family
Paratanaidae to be described from the Hawaiian Islands. Aparatanais hawaiensis is
distinguished from the other species of the genus by the setation of the antenna,
maxilliped, chela, and pereopods. Metatanais spinipropodus is distinguished from
the other three members of its genus by its chela having a strongly developed,
chisel-like, spiniform seta on the inner face of propodus near the sub-distal
margin of the fixed finger. The Hawaiian occurrence of M. spinipropodus extends
the range for the genus Metatanais well-eastward into the mid-Pacific Ocean. This
study presents the first description of a male attributable to the genus
Aparatanais.
PMID- 27615685
TI - A new genus of katydid from the Amazon Rainforest (Orthoptera: Tettigoniidae;
Phaneropterinae; Steirodontini): Ninth contribution to the suprageneric
organization of the Neotropical phaneropterines.
AB - Emsleyfolium diasae n. gen. et n. sp., from the Brazilian, Colombian, Ecuadorian
and Peruvian Amazon is described in this contribution. This new genus is
morphologically very similar to Stilpnochlora, but is distinguished from the
other Steirodiontini genera by its cone-head (similar to some genera of subfamily
Conocephalinae, e.g. Neoconocephalus and Bucrates), modification of the tenth
tergite into three lobes and absence of styles on subgenital plate. Thanatosis
behavior is described as a defense mechanism.
PMID- 27615687
TI - Contribution of soil respiration to the global carbon equation.
AB - Soil respiration (Rs) is the second largest carbon flux next to GPP between the
terrestrial ecosystem (the largest organic carbon pool) and the atmosphere at a
global scale. Given their critical role in the global carbon cycle, Rs
measurement and modeling issues have been well reviewed in previous studies. In
this paper, we briefly review advances in soil organic carbon (SOC) decomposition
processes and the factors affecting Rs. We examine the spatial and temporal
distribution of Rs measurements available in the literature and found that most
of the measurements were conducted in North America, Europe, and East Asia, with
major gaps in Africa, East Europe, North Asia, Southeast Asia, and Australia,
especially in dry ecosystems. We discuss the potential problems of measuring Rs
on slope soils and propose using obliquely-cut soil collars to solve the existing
problems. We synthesize previous estimates of global Rs flux and find that the
estimates ranged from 50 PgC/yr to 98 PgC/yr and the error associated with each
estimation was also high (4 PgC/yr to 33.2 PgC/yr). Using a newly integrated
database of Rs measurements and the MODIS vegetation map, we estimate that the
global annual Rs flux is 94.3 PgC/yr with an estimation error of 17.9 PgC/yr at a
95% confidence level. The uneven distribution of Rs measurements limits our
ability to improve the accuracy of estimation. Based on the global estimation of
Rs flux, we found that Rs is highly correlated with GPP and NPP at the biome
level, highlighting the role of Rs in global carbon budgets.
PMID- 27615686
TI - Delayed Propionibacterium acnes surgical site infections occur only in the
presence of an implant.
AB - Whether Propionibacterium acnes (P. acnes) causes surgical-site infections (SSI)
after orthopedic surgery is controversial. We previously reported that we
frequently find P. acnes in intraoperative specimens, yet none of the patients
have clinically apparent infections. Here, we tracked P. acnes for 6 months in a
mouse osteomyelitis model. We inoculated P. acnes with an implant into the mouse
femur in the implant group; the control group was treated with the bacteria but
no implant. We then observed over a 6-month period using optical imaging system.
During the first 2 weeks, bacterial signals were detected in the femur in the
both groups. The bacterial signal completely disappeared in the control group
within 28 days. Interestingly, in the implant group, bacterial signals were still
present 6 months after inoculation. Histological and scanning electron-microscope
analyses confirmed that P. acnes was absent from the control group 6 months after
inoculation, but in the implant group, the bacteria had survived in a biofilm
around the implant. PCR analysis also identified P. acnes in the purulent
effusion from the infected femurs in the implant group. To our knowledge, this is
the first report showing that P. acnes causes SSI only in the presence of an
implant.
PMID- 27615688
TI - Detection of the cytochrome b mutation G143A in Irish Rhynchosporium commune
populations using targeted 454 sequencing.
AB - BACKGROUND: Rhynchosporium commune is a major fungal pathogen of barley crops,
and the application of fungicides, such as quinone outside inhibitors (QoIs),
plays an important role in crop disease control. The genetic mechanisms linked to
QoI resistance have been identified in the cytochrome b gene, with QoI resistance
conferred by the G143A substitution. The objective of this study was to develop a
high-throughput molecular assay to detect and identify mutations associated with
QoI resistance within the Irish R. commune population. RESULTS: Leaf lesions of
R. commune sampled from 74 sites during 2009-2014 and isolates from 2006 and 2007
were screened for non-synonymous mutations of the cytochrome b gene using 454
targeted sequencing. The presence of the G143A substitution was confirmed in R.
commune samples at one site in 2013 and at four sites in 2014; however, the
frequency of the substitution in these samples was low (2-18%). The 454
sequencing results were confirmed by PCR-RFLP and Sanger sequencing. CONCLUSION:
The molecular assay that has been applied to this monitoring programme has shown
that the application of 454 next-generation sequencing offers the potential for
high throughput and accurate characterisation of non-synonymous mutations
associated with fungicide resistance in a crop pathogen. (c) 2016 Society of
Chemical Industry.
PMID- 27615689
TI - The theory of spin noise spectroscopy: a review.
AB - Direct measurements of spin fluctuations are becoming the mainstream approach for
studies of complex condensed matter, molecular, nuclear, and atomic systems. This
review covers recent progress in the field of optical spin noise spectroscopy
(SNS) with an additional goal to establish an introduction into its theoretical
foundations. Various theoretical techniques that have been recently used to
interpret results of SNS measurements are explained alongside examples of their
applications.
PMID- 27615691
TI - Spin excitations in hole-overdoped iron-based superconductors.
AB - Understanding the overall features of magnetic excitation is essential for
clarifying the mechanism of Cooper pair formation in iron-based superconductors.
In particular, clarifying the relationship between magnetism and
superconductivity is a central challenge because magnetism may play a key role in
their exotic superconductivity. BaFe2As2 is one of ideal systems for such
investigation because its superconductivity can be induced in several ways,
allowing a comparative examination. Here we report a study on the spin
fluctuations of the hole-overdoped iron-based superconductors Ba1-xKxFe2As2 (x =
0.5 and 1.0; Tc = 36 K and 3.4 K, respectively) over the entire Brillouin zone
using inelastic neutron scattering. We find that their spin spectra consist of
spin wave and chimney-like dispersions. The chimney-like dispersion can be
attributed to the itinerant character of magnetism. The band width of the spin
wave-like dispersion is almost constant from the non-doped to optimum-doped
region, which is followed by a large reduction in the overdoped region. This
suggests that the superconductivity is suppressed by the reduction of magnetic
exchange couplings, indicating a strong relationship between magnetism and
superconductivity in iron-based superconductors.
PMID- 27615690
TI - Impact of Amidination on Peptide Fragmentation and Identification in Shotgun
Proteomics.
AB - Peptide amidination labeling using S-methyl thioacetimidate (SMTA) is
investigated in an attempt to increase the number and types of peptides that can
be detected in a bottom-up proteomics experiment. This derivatization method
affects the basicity of lysine residues and is shown here to significantly impact
the idiosyncracies of peptide fragmentation and peptide detectability. The unique
and highly reproducible fragmentation properties of SMTA-labeled peptides, such
as the strong propensity for forming b1 fragment ions, can be further exploited
to modify the scoring of peptide-spectrum pairs and improve peptide
identification. To this end, we have developed a supervised postprocessing
algorithm to exploit these characteristics of peptides labeled by SMTA. Our
experiments show that although the overall number of identifications are similar,
the SMTA modification enabled the detection of 16-26% peptides not previously
observed in comparable CID/HCD tandem mass spectrometry experiments without SMTA
labeling.
PMID- 27615692
TI - Structures and biological activities of the triterpenoids and sesquiterpenoids
from Alisma orientale.
AB - Sixteen triterpenoids and nine sesquiterpenoids were isolated from the rhizome of
Alisma orientale. Structures of 16-oxo-11-anhydroalisol A 24-acetate,
13beta,17beta-epoxy-24,25,26,27-tetranor-alisol A 23-oic acid, 1alphaH,5alphaH
guaia-6-ene-4beta,10beta-diol, and alisguaiaone were elucidated by comprehensive
spectroscopic data analysis. The cytotoxic, antibacterial, antifungal, anti
inflammatory, and alpha-glucosidase inhibitory activities of isolated terpenoids
were evaluated. Triterpenoids alisol A, alisol A 24-acetate, 25-O-ethylalisol A,
11-deoxyalisol A, alisol E 24-acetate, alisol G, alisol B 23-acetate and
sesquiterpenoids 1alphaH,5alphaH-guaia-6-ene-4beta,10beta-diol, 10-hydroxy-7,10
epoxysalvialane exhibited cytotoxicities against the three tested human cancer
cell lines with IC50 values ranging from 11.5 +/- 1.7 MUM to 76.7 +/- 1.4 MUM.
Triterpenoids alisol A, 25-O-ethylalisol A, 11-deoxyalisol A, alisol E 24
acetate, alisol G, and 25-anhydroalisol F showed antibacterial activities against
the Gram-positive strains Bacillus subtilis and Staphylococcus aureus with MIC
values of 12.5-100 MUg/mL. Sesquiterpenoid 4beta,10beta-dihydroxy-1alphaH,5betaH
guaia-6-ene exhibited antibacterial activity against B. subtilis with an MIC
value of 50 MUg/mL, and 10-hydroxy-7,10-epoxysalvialane exhibited activity
against S. aureus with an MIC value of 100 MUg/mL. Compounds 16-oxo-11
anhydroalisol A 24-acetate, alisol F, 25-anhydroalisol F, and alisguaiaone
exhibited inhibitory effects on lipopolysaccharide-induced NO production in RAW
264.7 macrophage cells. None of the compounds showed obvious inhibitory activity
against alpha-glucosidase.
PMID- 27615693
TI - Notch1 in oral squamous cell carcinoma.
AB - Notch signaling has been reported to be involved in several types of malignant
tumors. However, the role and activation mechanisms of Notch signaling in oral
squamous cell carcinoma (OSCC) remain poorly characterized. The present review
focuses on the dual role of Notch signaling in OSCC. A number of expression and
functional analyses demonstrated that Notch1 plays a crucial role in development
and progression of OSCC. On the other hand, a tumor suppressive role of Notch1
was also suggested from studies, based on deep sequencing of cancer genomes.
Interestingly, although some Notch1 mutations overlap in tumors from Caucasian
and Asian patients, the overall spectrum of such mutations is vastly different
between these cohorts. Accumulating evidence suggests that variation of Notch1
mutation signature may determine the role of Notch signaling in OSCC. As Notch is
thought to act as an oncogene in a subset of OSCC, but also has a tumor
suppression role, the role of Notch in OSCC seems to be highly context dependent.
PMID- 27615694
TI - [Not Available].
PMID- 27615695
TI - [Not Available].
PMID- 27615696
TI - [Therapeutic touch and anorexia nervosa].
AB - An innovative practice, therapeutic touch has been used for around ten years in
the treatment of eating disorders. Delivered by nurse clinicians having received
specific training, this approach is based on nursing diagnoses which identify the
major symptoms of this pathology. The support is built around the body and its
perceptions. Through the helping relationship, it mobilises the patient's
resources to favour a relationship of trust, a letting-go, physical,
psychological and emotional relaxation, and improves the therapeutic alliance.
PMID- 27615698
TI - [Theatre as a form of physical mediation].
AB - In psychiatric care, the specific physical relationship that the nursing staff
have with people in distress must be taken into account. In a workshop, this
physical relationship extends to the group. In a theatre workshop, it is even
more complex as the body is engaged in play, in character and sometimes in front
of an audience. This article describes the experience of participants and nurses
with regard to the particularity of the body within the theatre setting.
PMID- 27615697
TI - [Relaxation, a complementary approach for mental health nurses].
AB - Relaxation is arousing growing interest in mental health. Its positive effects
are in line with an active approach which brings together body and mind and place
the individual back on the path of self-awareness. The relationship with the
patient constitutes the "therapeutic we" ensuring its therapeutic importance. It
represents a complementary and original approach to caring.
PMID- 27615699
TI - [Sophrology and psychiatry].
AB - A relatively new discipline in the field of human sciences, sophrology seeks,
through a physical as well as mental approach, to awaken awareness while
energising the patient's resources and capacities. In psychiatry, it favours the
development of body awareness and the positive activation of the mental
structures, for the greater wellbeing of the patient.
PMID- 27615700
TI - [Discussion around the use of yoga in psychiatry].
AB - Many mind-body practices have recently been introduced into psychiatric care
including yoga. An experiment in the field addresses the issue of the
organisation and applications of this discipline, and envisages the possibility
of extending the scope of indications.
PMID- 27615701
TI - [Beyond suffering, schizophrenic improvisation and therapeutic challenges].
AB - Led jointly by an actress and an occupational therapist, an 'improvisation'
activity has been set up within the Sainte-Anne University Hospital SHU Sector 14
for hospitalised patients, on medical prescription. This containing environment
provides psychological support and encourages patients with schizophrenia to
explore their creativity and to 'let go' so as to discover new physical
possibilities. The group thereby becomes a support for the relationship and the
development of verbal and non-verbal communication.
PMID- 27615702
TI - [Cognitive remediation and nursing care].
AB - Therapies based on cognitive remediation integrate psychiatric care. Cognitive
remediation helps to ease cognitive disorders and enable patients to improve
their day-to-day lives. It is essential to complete nurses' training in this
field. This article presents the example of a patient with schizophrenia who
followed the Cognitive Remediation Therapy programme, enabling him to access
mainstream employment.
PMID- 27615704
TI - Quantum dot spin coherence governed by a strained nuclear environment.
AB - The interaction between a confined electron and the nuclei of an optically active
quantum dot provides a uniquely rich manifestation of the central spin problem.
Coherent qubit control combines with an ultrafast spin-photon interface to make
these confined spins attractive candidates for quantum optical networks. Reaching
the full potential of spin coherence has been hindered by the lack of knowledge
of the key irreversible environment dynamics. Through all-optical Hahn echo
decoupling we now recover the intrinsic coherence time set by the interaction
with the inhomogeneously strained nuclear bath. The high-frequency nuclear
dynamics are directly imprinted on the electron spin coherence, resulting in a
dramatic jump of coherence times from few tens of nanoseconds to the microsecond
regime between 2 and 3 T magnetic field and an exponential decay of coherence at
high fields. These results reveal spin coherence can be improved by applying
large magnetic fields and reducing strain inhomogeneity.
PMID- 27615705
TI - Evolving serodiagnostics by rationally designed peptide arrays: the Burkholderia
paradigm in Cystic Fibrosis.
AB - Efficient diagnosis of emerging and novel bacterial infections is fundamental to
guide decisions on therapeutic treatments. Here, we engineered a novel rational
strategy to design peptide microarray platforms, which combines structural and
genomic analyses to predict the binding interfaces between diverse protein
antigens and antibodies against Burkholderia cepacia complex infections present
in the sera of Cystic Fibrosis (CF) patients. The predicted binding interfaces on
the antigens are synthesized in the form of isolated peptides and chemically
optimized for controlled orientation on the surface. Our platform displays
multiple Burkholderia-related epitopes and is shown to diagnose infected
individuals even in presence of superinfections caused by other prevalent CF
pathogens, with limited cost and time requirements. Moreover, our data point out
that the specific patterns determined by combined probe responses might provide a
characterization of Burkholderia infections even at the subtype level
(genomovars). The method is general and immediately applicable to other bacteria.
PMID- 27615707
TI - Botulinum toxin injection for contouring shoulder.
PMID- 27615708
TI - In vivo evaluation of lipid-based formulations for oral delivery of apomorphine
and its diester prodrugs.
AB - In the present study, the differences in oral absorption of apomorphine and its
diester prodrugs and the effect of lipid-based formulations on the absorption of
apomorphine or its prodrugs were investigated. Apomorphine, dilauroyl apomorphine
(DLA) and dipalmitoyl apomorphine (DPA) were orally administered (0.24mmol/kg) to
rats as: DLA-o/w emulsion, DPA-o/w emulsion, apomorphine-o/w emulsion,
apomorphine aqueous suspension, DLA-Maisine, DLA-soybean oil, DLA-self
emulsifying drug delivery systems (SEDDS), and DLA-w/o emulsion. The o/w and w/o
emulsion consisted of Maisine 35-1 emulsified with water in 1:3 and 4:1 ratio,
respectively. Tmax of diesters was significantly increased (p<=0.05) compared to
apomorphine in o/w emulsion, suggesting that esterification yielded prolonged
drug absorption. Cmax, AUC and the relative bioavailability of apomorphine after
DLA-SEDDS administration was higher (p<=0.05) than after DLA-w/o administration,
indicating that triglycerides and surfactants improved the oral absorption of
DLA. Similarly, Cmax and AUC after dosing apomorphine-o/w were significantly
higher (p<=0.05) than that of aqueous suspension. This suggested that lipids and
lipolysis products possibly aided apomorphine micellar solubilization in
intestinal fluids. A combination of prodrug strategy and lipid-based formulations
facilitated a higher and prolonged absorption of apomorphine from its diester
prodrugs.
PMID- 27615706
TI - Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L)
mutation treated with everolimus therapy.
AB - Pituitary adenomas are the commonest intracranial tumor, but metastases are rare
(0.2% yearly incidence) and portend poor prognosis. CAPecitabine and TEMozolomide
improved outcomes for neuroendocrine tumors. However, no chemotherapy is approved
for refractory pituitary carcinomas. Next-generation sequencing revealed an
actionable mTOR pathway STK11 mutation in a woman with adrenocorticotropic
hormone-secreting pituitary carcinoma refractory to six resections, radiation and
CAPecitabine and TEMozolomide. Given efficacy in preclinical pancreatic cancer
models with STK11 mutations, she received radiation and everolimus leading to
clinical improvement and stability on MRI and PET for >6 months. She ultimately
expired from widely metastatic disease. Next-generation sequencing can identify
actionable mutations in rare or treatment refractory tumors. Earlier targeted
therapy may improve outcomes.
PMID- 27615709
TI - Design, fabrication and biomedical applications of zein-based nano/micro-carrier
systems.
AB - Nano/micro-carrier systems have shown promising application in the biomedical
field as various delivery carriers. The composite material and fabrication method
determine their microstructures, properties and thus their potential
applications. Since approved as tablet coating material by the U.S. Food and Drug
Administration (US-FDA), zein has been widely investigated as one of protein
based materials in the past few decades. Zein is renewable, biodegradable and
relatively inexpensive in comparison with animal proteins (e.g., gelatin and
albumin). This paper reviews the current landscape of zein-based nano/micro
carrier systems, with particular emphasis on nano/microparticles,
nano/microcapsules and their design, fabrication, assembly mechanisms and
biomedical applications especially for controlled drug delivery. The benefits,
challenges and related solutions of zein-based colloidal carrier systems are also
discussed. In addition, investigations on the molecular structure,
biocompatibility and immunogenicity of zein are summarized and discussed.
PMID- 27615710
TI - Longitudinal fluctuation in mammographic percent density differentiates between
interval and screen-detected breast cancer.
AB - Interval breast cancer (IC) has a more aggressive phenotype and higher mortality
than screen-detected cancer (SDC). In this case-case study, we investigated
whether the size of longitudinal fluctuations in mammographic percent density (PD
fluctuation) was associated with the ratio of IC versus SDC among screened women
with breast cancer. The primary study population consisted of 1,414
postmenopausal breast cancer cases, and the validation population of 1,241 cases.
We calculated PD fluctuation as the quadratic mean of deviations between actual
PD and the long-term trend estimated by a mixed effects model. In a logistic
regression model we examined the association between PD fluctuation and IC versus
SDC including adjustments for PD at last screening, age at diagnosis, BMI and
hormone replacement therapy. All statistical tests were two-sided. There were 385
IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44
and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was
associated with an increased ratio of IC versus SDC, with an estimated per
standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95%
CI = 1.04-1.38) in the validation population. In screened women with breast
cancer, high fluctuation in mammographic percent density was associated with an
increased ratio of IC versus SDC. Whether this is entirely related to a reduced
mammographic detectability or to a biological phenotype promoting faster tumor
growth remains to be elucidated.
PMID- 27615711
TI - A home-based physical activity intervention using activity trackers in survivors
of childhood cancer: A pilot study.
AB - BACKGROUND: Over 70% of childhood cancer survivors develop late complications
from therapy, many of which can be mitigated by physical activity. Survivors
engage in exercise at similar or lower rates than their sedentary healthy peers.
We piloted a novel home-based exercise intervention with a motivational activity
tracker. We evaluated (i) feasibility, (ii) impact on activity levels and
physical fitness, and (iii) barriers, preferences, and beliefs regarding physical
activity. METHODS: Childhood cancer survivors currently 15 years or older and not
meeting the Centers for Disease Control and Prevention physical activity
guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm * 1.8 cm
motivational activity tracker, daily for 6 months. Baseline and follow-up
evaluations included self-report surveys, an Actigraph accelerometer for 7 days,
and a VO2 maximum test by cardiac stress test. RESULTS: Nineteen participants
were enrolled (13.4% participation rate) with a mean age of 24.3 +/- 5.8 years
(range 15-35). Four participants withdrew with a 79% retention rate. Participants
wore the Fitbit an average of 19.0 +/- 4.7 days per month during months 1-3 and
15.0 +/- 7.9 days per month during months 4-6. Total weekly moderate to vigorous
physical activity increased from 265.6 +/- 117.0 to 301.4 +/- 135.4 min and VO2
maximum increased from 25.7 +/- 7.7 to 27.2 +/- 7.4 ml/kg/min. These changes were
not statistically significant (P = 0.47 and 0.30, respectively). Survey responses
indicated no change in barriers, preferences, and beliefs regarding physical
activity. CONCLUSIONS: This pilot study of a motivational activity tracker
demonstrated feasibility as measured by participant retention, receptivity, and
belief of utility. Future studies with a large sample size are needed to
demonstrate the efficacy and sustainability of this intervention.
PMID- 27615712
TI - Health-related quality-of-life after transapical transcatheter aortic valve
implantation.
AB - PURPOSE: Transcatheter aortic valve implantation (TA-TAVI) is a well-established
treatment for aortic valve stenosis in high-risk patients and indications have
been continuously expanding to also include intermediate-risk patients. However,
in low-risk patients, experiences are still sparse and although clinical outcomes
have been shown favorable results, HRQoL has remained unexplored. The aim of this
report was to describe the long-term health-related quality-of-life (HRQoL) in
low-risk patients randomized to TA-TAVI or surgical aortic valve replacement
(SAVR). METHODS: In a prospective, randomized trial, patients with aortic valve
stenosis were randomized to either TA-TAVI or SAVR. TA-TAVI was performed through
a mini thoracotomy with the introduction of prosthesis via the apex of the heart
and antegradely advancement over the pre-dilated native valve. SAVR was performed
during cardiopulmonary bypass with resection of the native valve and replacement
with a prosthesis valve through a median sternotomy. Afterwards, patients were
followed yearly with echocardiography and HRQoL assessment. RESULTS: A total of
58 patients were included; 29 patients for TA-TAVI and 29 patients for SAVR. The
only difference in HRQoL was found in the physical component summary after 1
year; 44 +/- 9 in the TA-TAVI group compared with 36 +/- 9 in the SAVR group, p =
.03. There were no differences in any of the remaining timepoints in neither
physical nor mental component summary, p = .19 and p = .98, respectively, and
there were no differences in survival during the 5 years. CONCLUSIONS: In low
risk patients with aortic valve stenosis undergoing TA-TAVI, no differences
appeared in HRQoL compared with SAVR during a 5-year follow-up period.
PMID- 27615713
TI - Molecular detection of Sarcocystis aucheniae in the blood of llamas from
Argentina.
AB - Sarcocystis aucheniae are apicomplexan protozoa that infect South American
camelids (SACs), giving rise to macroscopic cysts similar to rice grains in
skeletal muscles. Visual detection of macrocysts in slaughtered animals hampers
commercialization of SAC meat, a highly relevant economic exploitation for Andean
rural families. Importantly, the consumption of undercooked S. aucheniae-infested
meat causes gastroenteritis. A carnivore definitive host, possibly the dog,
acquires the parasite when feeding on infected SAC meat, and later eliminates
infective oocysts in its feces. The parasite cycle is completed when SACs ingest
contaminated water or pastures. We hypothesized that parasite DNA can be detected
in SAC blood using molecular methods. In order to test this hypothesis, a
seminested PCR format was specifically designed to target the hypervariable 18S
rRNA gene region of S. aucheniae. PCR conditions were optimized using genomic DNA
extracted from macrocyst bradyzoites. A detection limit of up to 1 parasite in
10MUl of llama blood was established based on DNA samples extracted from aliquots
of S. aucheniae bradyzoite-spiked non-infected llama blood. The seminested PCR
allowed to detect natural infections of S. aucheniae in llama blood samples
originating in the Andean flatlands of Argentina. Specific amplification of S.
aucheniae DNA was corroborated by amplicon sequencing. This is the first report
of S. aucheniae detection in llama blood, which provides a valuable diagnostic
tool for epidemiological studies and for the evaluation of the efficacy of
control measures for this parasitosis.
PMID- 27615714
TI - Assessment of the in vitro bioactive properties of lactic acid bacteria isolated
from native ecological niches of Ecuador.
AB - Lactic acid bacteria are known for their biotechnological potential. In various
regions of Ecuador numerous indigenous biological resources are largely
undocumented. In this study, we evaluated the potential probiotic characteristics
and antagonistic in vitro properties of some lactic acid bacteria from native
niches of the subtropical rain forests of Ecuador. These isolates were identified
according to their morphological properties, standard API50CH fermentation
profile and RAPD-DNA polymorphism pattern. The selected isolates were further
evaluated for their probiotic potential. The isolates grew at 15 degrees C and 45
degrees C, survived at a pH ranging from 2.5 to 4.5 in the presence of 0.3% bile
(>90%) and grew under sodium chloride conditions. All selected isolates were
sensitive to ampicillin, amoxicillin and cefuroxime and some showed resistance to
gentamicin, kanamycin and tetracycline. Moreover, the agar well diffusion assay
showed that the supernatant of each strain at pH 3.0 and pH 4.0, but not at pH
7.0 exhibited increased antimicrobial activity (inhibition zone >15mm) against
two foodborne pathogens, Escherichia coli and Salmonella spp. To our knowledge,
this is the first report describing the antagonistic activity against two
foodborne pathogens and the probiotic in vitro potential of lactic acid bacteria
isolated from native biota of Ecuador.
PMID- 27615715
TI - Using the breakage matrix approach for monitoring the break release in the wheat
flour milling process.
AB - BACKGROUND: The breakage matrix approach is a mathematical tool to relate input
and output particle size distribution from a milling operation. Adjustment of the
break release in the flour milling process is extremely important because it
affects granulation and quality characteristics of the stock and hence the total
results and balance of the mill. In this study the breakage matrix approach has
been used for the purpose of controlling the release on the front passages of the
break system in the flour milling process. RESULTS: It has been established that,
for any particle size distribution of wheat, it is possible to predict break
releases together with the distribution of the release size fractions by using
the breakage matrices. Also, the reversibility of this approach is examined, that
is the possibility to identify the wheat particle size distribution that would
result in desired break releases and/or the desired yields of different sized
intermediate stocks under the given set of milling conditions. CONCLUSION: It is
confirmed that the breakage matrix approach can be successfully used to predict
the break releases. The reverse breakage matrix concept allows the determination
of the wheat particle size distribution which would result in a targeted break
release. (c) 2016 Society of Chemical Industry.
PMID- 27615716
TI - Asymptomatic Clostridium difficile colonization in two Australian tertiary
hospitals, 2012-2014: prospective, repeated cross-sectional study.
AB - OBJECTIVES: To investigate the prevalence and risk factors for asymptomatic
toxigenic (TCD) and nontoxigenic Clostridium difficile (NTCD) colonization in a
broad cross section of the general hospital population over a 3-year period.
METHODS: Patients without diarrhoea admitted to two Australian tertiary hospitals
were randomly selected through six repeated cross-sectional surveys conducted
between 2012 and 2014. Stool specimens were cultured under anaerobic conditions,
and C. difficile isolates were tested for the presence of toxin genes and
ribotyped. Patients were then grouped into noncolonized, TCD colonized or NTCD
colonized for identifying risk factors using multinomial logistic regression
models. RESULTS: A total of 1380 asymptomatic patients were enrolled; 76 patients
(5.5%) were TCD colonized and 28 (2.0%) were NTCD colonized. There was a
decreasing annual trend in TCD colonization, and asymptomatic colonization was
more prevalent during the summer than winter months. TCD colonization was
associated with gastro-oesophageal reflux disease (relative risk ratio (RRR) =
2.20; 95% confidence interval (CI) 1.17-4.14), higher number of admissions in the
previous year (RRR = 1.24; 95% CI 1.10-1.39) and antimicrobial exposure during
the current admission (RRR = 2.78; 95% CI 1.23-6.28). NTCD colonization was
associated with chronic obstructive pulmonary disease (RRR = 3.88; 95% CI 1.66
9.07) and chronic kidney failure (RRR = 5.78; 95% CI 2.29-14.59). Forty-eight
different ribotypes were identified, with 014/020 (n = 23), 018 (n = 10) and 056
(n = 6) being the most commonly isolated. CONCLUSIONS: Risk factors differ
between patients with asymptomatic colonization by toxigenic and nontoxigenic
strains. Given that morbidity is largely driven by toxigenic strains, this novel
finding has important implications for disease control and prevention.
PMID- 27615717
TI - Long term detection of seasonal influenza RNA in faeces and intestine.
PMID- 27615718
TI - mcr-1 is borne by highly diverse Escherichia coli isolates since 2004 in food
producing animals in Europe.
AB - OBJECTIVES: In November 2015, a plasmid-mediated colistin resistance, MCR-1, was
described in animals, food and humans in China, and it was considered as a
potential emerging threat to public health. Therefore, we screened for the mcr-1
gene a European collection of colistin-resistant Escherichia coli (n=218) and
Salmonella spp. (n=74) isolated from diseased food-producing animals between 2004
and 2014 and characterized the mcr-1-positive clones. METHODS: Screening for mcr
1 gene was performed by PCR on isolates for which inhibition diameter was <15 mm
around a 50 MUg disk of colistin. Positive E. coli isolates were then
characterized by phylogrouping, multilocus sequence typing and pulsed-field gel
electrophoresis typing. Antibiotic susceptibility was determined by disk
diffusion testing or by broth microdilution. RESULTS: Among the collection, 42 E.
coli and three Salmonella spp. were positive for mcr-1, with continuous detection
since 2004 mainly from bovine and swine digestive infections. Most of the mcr-1
positive strains were resistant to amoxicillin and cotrimoxazole but remained
susceptible to cephalosporins, carbapenems and piperacillin/tazobactam. All but
one isolate were resistant to colistin, with a minimum inhibitory concentration
of >2 mg/L. Most of the mcr-1-positive E. coli belonged to the phylogroup A with
two prevalent clonal complexes, CC10 and CC165, in which sequence type 10 and
sequence type 100 were overrepresented and pulsed-field gel electrophoresis
typing revealed a high diversity of pulsotypes. CONCLUSIONS: MCR-1 was detected
yearly in European food-producing animal since 2004 with a high diversity of
pulsotypes supporting the dissemination of mcr-1 via plasmids.
PMID- 27615720
TI - Molecular history of plague.
AB - Plague, a deadly zoonose caused by the bacterium Yersinia pestis, has been firmly
documented in 39 historical burial sites in Eurasia that date from the Bronze Age
to two historical pandemics spanning the 6th to 18th centuries.
Palaeomicrobiologic data, including gene and spacer sequences, whole genome
sequences and protein data, confirmed that two historical pandemics swept over
Europe from probable Asian sources and possible two-way-ticket journeys back from
Europe to Asia. These investigations made it possible to address questions
regarding the potential sources and routes of transmission by completing the
standard rodent and rodent-flea transmission scheme. This suggested that plague
was transmissible by human ectoparasites such as lice, and that Y. pestis was
able to persist for months in the soil, which is a source of reinfection for
burrowing mammals. The analyses of seven complete genome sequences from the
Bronze Age indicated that Y. pestis was probably not an ectoparasite-borne
pathogen in these populations. Further analyses of 14 genomes indicated that the
Justinian pandemic strains may have formed a clade distinct from the one
responsible for the second pandemic, spanning in Y. pestis branch 1, which also
comprises the third pandemic strains. Further palaeomicrobiologic studies must
tightly connect with historical and anthropologic studies to resolve questions
regarding the actual sources of plague in ancient populations, alternative routes
of transmission and resistance traits. Answering these questions will broaden our
understanding of plague epidemiology so we may better face the actuality of this
deadly infection in countries where it remains epidemic.
PMID- 27615719
TI - Molecular epidemiology of Campylobacter jejuni infection in Israel-a nationwide
study.
AB - The incidence of Campylobacter infection in Israel, particularly among children
<2 years of age, has risen over the last decade and became one of the highest
among industrialized countries. This study explored the molecular epidemiology of
Campylobacter jejuni in Israel over a decade (2003-2012) using multilocus
sequence typing (MLST) combined with demographic metadata. Representative
clinical isolates (438) from a large national repository together with selected
veterinary isolates (74) were subject to MLST. The distribution of age groups,
ethnicity and clinical source across various genotypes was evaluated using
Poisson modelling. The 512 studied isolates were assigned 126 distinct sequence
types (STs) (18.8% novel STs) grouped into 21 clonal complexes (CCs). Most human,
poultry and bovine STs clustered together in the leading CCs. Three dominant STs
(ST21, ST6608, ST4766) were detected only since 2006. Patients infected with the
leading CCs were similarly distributed along densely populated areas. The
frequency of blood isolates was higher in patients infected with CC353 (relative
rate (RR)=2.0, 95% CI 1.03-3.9, adjusted p value (adj.p) 0.047) and CC42 (RR=4.4,
95% CI 1.7-11.6, adj.p 0.018) and lower with CC257 (RR=0.3, 95% CI 0.1-0.9, adj.
p 0.047). The distribution of age groups and ethnicity also varied across the
leading CCs. In conclusion, C. jejuni isolates in a national sample appeared
highly diverse with a high proportion of new STs. Phylogenic analysis was
compatible with poultry and cattle as possible food sources of clinical
infection. Demographic characteristics of the infected patients coupled with
strain invasiveness across different genotypes revealed a complex epidemiology of
C. jejuni transmission in Israel.
PMID- 27615721
TI - Incidental detection of a urinary Escherichia coli isolate harbouring mcr-1 of a
patient with no history of colistin treatment.
PMID- 27615722
TI - Combination antimicrobial therapy in patients with Staphylococcus aureus
bacteraemia-a post hoc analysis in 964 prospectively evaluated patients.
AB - OBJECTIVES: The evidence for using combination antimicrobial therapy (CoRx) in
Staphylococcus aureus bacteraemia (SAB) is limited. We aimed to investigate
whether CoRx is associated with higher survival or lower SAB-related late
complications. METHODS: We performed a post hoc analysis of a prospective SAB
cohort study. CoRx was defined as a cell wall-active antistaphylococcal agent
plus either rifampicin, a fluoroquinolone, fosfomycin or an aminoglycoside. To
adjust for survivor bias multivariable Cox models that included CoRx as a time
dependent covariable were calculated. RESULTS: Of 964 evaluable patients, 512
(53%) received CoRx, most of them (301/512, 59%) rifampicin-containing CoRx. All
cause mortality after 30 and 90 days was similar for the two groups, although the
patients in the CoRx group had more often endocarditis, deep-seated or
disseminated infections and severe sepsis/septic shock. For the entire cohort,
only age, comorbidity and severe sepsis/septic shock were associated with a
higher mortality and infectious disease consultation, but not CoRx with a lower
mortality. However, in the subgroup of patients with implanted foreign bodies or
devices CoRx was independently associated with a lower mortality at 30 days
(hazard ratio 0.6, 95% confidence interval 0.3-1.1) and at 90 days (hazard ratio
0.6, 95% confidence interval 0.4-0.9). SAB-related late complications in this
subgroup occurred in 15 (10.6%) of 142 patients in the monotherapy group vs. nine
(4.5%) of 202 patients in the CoRx group (p 0.03). CONCLUSIONS: In a setting of
optimized management of adult patients with SAB secured by infectious disease
consultations, this observational study could not prove CoRx to be independently
associated with improved survival or reduced late complications in the entire
cohort. However, administration of CoRx may be associated with lower mortality
and fewer SAB-related late complications in the subgroup of patients with
implanted foreign bodies or devices. Prospective randomized trials should be
performed to prove this benefit.
PMID- 27615725
TI - Turn-On Colorimetric Platform for Dual Activity Detection of Acid and Alkaline
Phosphatase in Human Whole Blood.
AB - The activity detection of acid phosphatase (ACP) and alkaline phosphatase (ALP)
is of great importance to the diagnosis and prognosis of related diseases. In
this work, we report for the first time a turn-on colorimetric platform for the
activity detection of ACP and ALP, by exploiting Cu(BCDS)22-
(BCDS=bathocuproinedisulfonate) as the probe. The presence of ACP or ALP
dephosphorylates the substrate ascorbic acid 2-phosphate to produce ascorbic
acid, which then reduces Cu(BCDS)22- into Cu(BCDS)23- , leading to a turn-on
spectral absorption at 484 nm and a dramatic color change of the solution from
colorless to orange-red. The underlying metal-to-ligand charge-transfer mechanism
has been demonstrated by quantum mechanical computations. This platform allows a
rapid, sensitive readout of ACP and ALP activities within the dynamic range from
0 to 220 mU ml-1 . In addition, it is highly immune to false-positive results and
also highly selective. More importantly, it is applicable in the presence of
human serum and even whole blood samples. These results demonstrate that our
platform holds great potential in clinical practices and in the point-of-care
analysis.
PMID- 27615724
TI - Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus
infection?
AB - The aim of preventive measures against human immunodeficiency virus (HIV) is to
reduce the incidence of HIV infection in the general population and in high-risk
groups, such as men having sex with men (MSM), and to reduce the risk that a
given individual will contract or spread the virus. Male and female condoms, post
exposure prophylaxis and circumcision are preventive methods currently recognized
or promoted worldwide. Although modest success has been reported in a phase-III
vaccine trial, other methods are being evaluated, such as vaginal and rectal
microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results
from prevention trials, especially those focusing on PrEP and particularly on
recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%
86%) is strongly correlated with adherence and plasma concentrations of
antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant
strains is mainly reported in individuals with an undiagnosed HIV infection using
PrEP. PrEP is now strongly recommended in WHO prevention programmes for
individuals at substantial risk for HIV with a view to controlling this epidemic
by 2030.
PMID- 27615726
TI - HPLC Quantification of astaxanthin and canthaxanthin in Salmonidae eggs.
AB - Astaxanthin and canthaxanthin are naturally occurring antioxidants referred to as
xanthophylls. They are used as food additives in fish farms to improve the
organoleptic qualities of salmonid products and to prevent reproductive diseases.
This study reports the development and single-laboratory validation of a rapid
method for quantification of astaxanthin and canthaxanthin in eggs of rainbow
trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis M.). An
advantage of the proposed method is the perfect combination of selective
extraction of the xanthophylls and analysis of the extract by high-performance
liquid chromatography and photodiode array detection. The method validation was
carried out in terms of linearity, accuracy, precision, recovery and limits of
detection and quantification. The method was applied for simultaneous
quantification of the two xanthophylls in eggs of rainbow trout and brook trout
after their selective extraction. The results show that astaxanthin accumulations
in salmonid fish eggs are larger than those of canthaxanthin. As the levels of
these two xanthophylls affect fish fertility, this method can be used to improve
the nutritional quality and to minimize the occurrence of the M74 syndrome in
fish populations.
PMID- 27615723
TI - TLR4 genetic variation is associated with inflammatory responses in Gram-positive
sepsis.
AB - OBJECTIVES: To identify important pathogen recognition receptor (PRR) pathways
regulating innate immune responses and outcome in Staphylococcus aureus sepsis.
METHODS: We analysed whether candidate PRR pathway genetic variants were
associated with killed S. aureus-induced cytokine responses ex vivo and performed
follow-up in vitro studies. We tested the association of our top-ranked variant
with cytokine responses and clinical outcomes in a prospective multicentre cohort
of patients with staphylococcal sepsis. RESULTS: An intronic TLR4 polymorphism
and expression quantitative trait locus, rs1927907, was highly associated with
cytokine release induced by stimulation of blood from healthy Thai subjects with
S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-kappaB activation
in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-alpha
release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing
antibody, but in a monocyte cell line, TNF-alpha was reduced by knockdown of
TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with
higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S.
aureus-induced responses in blood were most highly correlated with responses to
Gram-negative stimulants whole blood. CONCLUSIONS: A genetic variant in TLR4 is
associated with cytokine responses to S. aureus ex vivo and plasma cytokine
levels and respiratory failure in staphylococcal sepsis. While S. aureus does not
express lipopolysaccharide or activate TLR4 directly, the innate immune response
to S. aureus does appear to be modulated by TLR4 and shares significant
commonality with that induced by Gram-negative pathogens and lipopolysaccharide.
PMID- 27615727
TI - Strigolactones as Part of the Plant Defence System.
AB - Strigolactones (SLs) are plant hormones, described as regulators of plant growth
and development. Recently, it was proposed that these hormones might also be
involved in the biotic stress response. However, SLs do not have a universal role
in plant protection, instead only playing a part in resistance to specific
pathogens.
PMID- 27615728
TI - Evaluation of the relation between preapoptotic sperm rate in ejaculate and
intrauterine insemination success rate in patients with unexplained infertility.
AB - The parameters measured in the standard semen analysis may be insufficient for
exact differentiation between fertile and infertile men. Therefore, we assume
that the high rate of apoptotic sperm in ejaculate may play a role on the
aetiology of unexplained infertility. Couples with unexplained infertility
treated by ovulation induction and intrauterine insemination were consecutively
enrolled (n = 94). To determine the proapoptotic sperm rate, the ejaculate from
patients was stained with annexin V. Thirteen of the 94 couples (13.8%) conceived
after intrauterine insemination. The annexin V-positive sperm rate was found to
be 20.0% in the whole group. In women failing to conceive, the annexin V-positive
sperm rate was 20.8% compared to 15.7% in patients who achieved pregnancy.
Although there is a trend towards higher preapoptotic sperm rate in couples
failing to get pregnant with insemination, the difference did not reach
statistical significance.
PMID- 27615729
TI - Efficacy of trabectedin for the treatment of liposarcoma.
AB - INTRODUCTION: Trabectedin (ET-743) is a synthetic marine derived alkylating
agent, extracted originally from a Caribbean Sea sponge. It is approved for the
treatment of Soft Tissue sarcomas (STS) in Europe and recently by the FDA for
liposarcomas and leiomyosarcomas. AREAS COVERED: Trabectedin has multiple
mechanisms of action, including one targeting the FUS-CHOP oncogene in
Myxoid/Round cell Liposarcomas. Numerous Phase I, II and III clinical trials have
been conducted with Trabectedin. It has been studied as monotherapy or in
combination with other chemotherapeutic agents. The recommended dose based on
clinical trials is 1.5 milligrams/m(2) continuous infusion over 24 hours once
every 3 weeks for STS with evidence of disease control in multiple clinical
trials at this dose. The most common Grade 3/4 toxicities include neutropenia and
transient noncumulative elevations of ALT and AST. Steroid pretreatment has shown
efficacy in reducing liver and bone marrow toxicity. In phase III testing
comparing trabectedin to dacarbazine, trabectedin was associated with a
significantly improved progression free survival rate in patients with advanced
lipo- and leiomyosarcomas. EXPERT OPINION: Trabectedin is an important new
addition to the limited treatment options currently available for STS, especially
for patients with liposarcoma that have progressed on standard chemotherapeutic
regimens.
PMID- 27615732
TI - Public health competences: from potential to action.
PMID- 27615730
TI - The Pentablock Amphiphilic Copolymer T1107 Prevents Aggregation of Denatured and
Reduced Lysozyme.
AB - Aggregation of denatured or unfolded proteins establishes a large energy barrier
to spontaneous recovery of protein form and function following traumatic injury,
tissue cryopreservation, and biopharmaceutical storage. Some tissues utilize
small heat shock proteins (sHSPs) to prevent irreversible aggregation, which
allows more complex processes to refold or remove the unfolded proteins. It is
postulated that large, amphiphilic, and biocompatible block copolymers can mimic
sHSP function. Reduced and denatured hen egg white lysozyme (HEWL) is used as a
model aggregating protein. The poloxamine T1107 prevents aggregation of HEWL at
37 degrees C by three complimentary measures. Structural analysis of denatured
HEWL reveals a partially folded conformation with preserved or promoted beta
sheet structures only in the presence of T1107. The physical association of T1107
with denatured HEWL, and the ability to prevent aggregation, is linked to the
critical micelle temperature of the polymer. The results suggest that T1107, or a
similar amphiphilic block copolymer, can find use as a synthetic chaperone to
augment the innate molecular repair mechanisms of natural cells.
PMID- 27615734
TI - Socio-demographic factors predicting HIV test seeking behaviour among MSM in 6 EU
cities.
AB - Background: HIV testing is generally accepted as being the lynchpin of a
prevention strategy to tackle the HIV epidemic among MSM. However, few studies
have analysed in detail the factors that influence HIV test seeking behaviour.
Methods: The objective of this article is to analyse the relationship between HIV
test seeking behaviour and individual, social and demographic factors in a sample
of MSM recruited though a multi-centre bio-behavioural cross-sectional study. A
multi-level analysis was conducted to identify factors associated with HIV test
seeking behaviour. Results: A total of 2400 men were included in the sample. Age,
self-reported sexual orientation, residence, household composition, educational
status and perceived homonegativity all seem to impact on test seeking behaviour.
Conclusions: The results suggest the need for more targeted testing promotion
strategies among MSM that take structural and environmental factors into
consideration, as part of a comprehensive public health strategy to address the
HIV epidemic.
PMID- 27615735
TI - Effects of annual influenza vaccination on mortality in patients with heart
failure.
AB - The objective was to evaluate the effect of influenza vaccine on all-cause
mortality in a cohort of patients with heart failure followed up in primary care
centres of the Community of Madrid, Spain, during the period 2006-10. Results of
the Cox proportional-hazard model were adjusted for age and sex and, after 1:1
nearest neighbour matching, for propensity score. The analysis was further
stratified by season. Having received annual influenza vaccine was associated
with a decreased risk of death during the influenza season (hazard ratio = 0.59,
95% CI = 0.41-0.84), but no protective effect was observed before or after the
influenza season.
PMID- 27615736
TI - Functional quantum dot-siRNA nanoplexes to regulate chondrogenic differentiation
of mesenchymal stem cells.
AB - : SOX9 plays an important role in mesenchymal condensations during the early
development of embryonic skeletons. However, its function in the chondrogenic
differentiation of adult mesenchymal stem cells (MSCs) has not been fully
investigated because SOX9 RNA interference in adult MSCs has seldom been studied.
This study used SOX9 gene as the target gene and the quantum dot (QD)-based
nanomaterial QD-NH2 (ZnS shell and poly-ethylene glycol (PEG) coating) with a
fluorescent tracer function as the gene carrier to transfect siSOX9 into MSCs
after sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo
SMCC) activation in vitro and in vivo. The results showed that QD-SMCC could
effectively bind and deliver siRNAs into the MSCs, followed by efficient siRNA
escape from the endosomes. The siRNAs released from QD-SMCC retained their
structural integrity and could effectively inhibit the targeted gene expression,
leading to reduced chondrogenic differentiation of MSCs and delayed cartilage
repair. QDs were excreted from living cells instead of dead cells, and the ZnS
shell and PEG coating layer greatly reduced the cytotoxicity of the QDs. The
transfection efficiency of QD-SMCC was superior to that of polyethylenimine
(PEI). In addition, QD-SMCC has an intrinsic signal for noninvasive imaging of
siRNA transport. The results indicate that SOX9 is imperative for the
chondrogenesis of MSCs and QD-SMCC has great potential for real-time tracking of
transfection. STATEMENT OF SIGNIFICANCE: In this study, we developed functional
quantum dot (QD) nanoplexes by sulfosuccinimidyl-4-(N-maleimidomethyl)
cyclohexane-1-carboxylate (sulfo-SMCC) activation of PEG-coated CdSe/ZnS QDs as
the gene carrier of siRNA to study the effect of SOX9 RNA interference on the
chondrogenic differentiation of MSCs. This study confirmed the importance of SOX9
in chondrogenesis, as evidenced by the findings that SOX9 knockdown significantly
inhibited the expression of cartilage-specific markers including acan and col2a1
in MSCs and further delayed cartilage repair. Moreover, QD-SMCC has an intrinsic
signal for noninvasive imaging of siRNA transport. The results indicate that SOX9
is imperative for the chondrogenesis of MSCs and QD-SMCC has great potential for
real-time tracking of transfection.
PMID- 27615737
TI - Electrophoretic deposition of colloidal particles on Mg with cytocompatibility,
antibacterial performance, and corrosion resistance.
AB - : Magnesium (Mg) has recently received increasing attention due to its unique
biological performance, including cytocompatibility, antibacterial and
biodegradable properties. However, rapid corrosion in physiological environment
and potential toxicity limits its clinical applications. To improve the corrosion
resistance meanwhile not compromise other excellent performance, self-assembled
colloidal particles were deposited onto magnesium surfaces in ethanol by a simple
and effective electrophoretic deposition (EPD) method. The fabricated functional
nanostructured coatings were investigated using Fourier transform infrared
spectroscopy (FTIR), X-ray diffraction (XRD) analyses, and scanning electron
microscopy (SEM). The electrochemical test, pH value, and Mg ion concentration
data show that the corrosion resistance of Mg samples is enhanced appreciably
after surface treatment. In vitro cellular response and antibacterial capability
of the modified Mg substrates are performed. Significantly increased cell
adhesion and viability are observed from the coated Mg samples, and the amounts
of adherent bacteria on the treated Mg surfaces diminish remarkably compared to
the bare Mg. Furthermore, the bare and coated Mg samples were implanted in New
Zealand white rabbits for 12 weeks to examine the in vivo long-term corrosion
performance and in situ inflammation behavior. The experiment results confirmed
that compared with bare Mg substrate the corrosion and foreign-body reactions of
the coated Mg samples were suppressed. The above results suggested that our
coatings, which effectively enhance the biocompatibility, antimicrobial
properties, and corrosion resistance of Mg substrate, provide a simple and
practical strategy to expedite clinical acceptance of biodegradableMg and its
alloys. STATEMENT OF SIGNIFICANCE: Biomedical Mg metals have been considered as
promising biodegradable implants because of their intended functions, such as
cytocompatibility, antibacterial, and biodegradable properties. However, rapid
corrosion in physiological environment limits their clinical applications.
Alloying and surface coatings have been used to reduce the degradation rate. But
this would compromise other excellent performance of Mg samples, including
antibacterial and anti-inflammatory activity. Thus, while the rapid degradation
of Mg samples must be solved, good antibacterial property and acceptable
cytocompatibility are also necessary. In this study, polymer-based coatings were
fabricated on Mg surfaces by electrophoretic deposition of poly(isobornyl
acrylate-co-dimethylaminoethyl methacrylate)/tannic acid (P(ISA-co-DMA)/TA)
colloidal particles. It suggested that the coating materials effectively improved
the biocompatibility, antimicrobial behavior, and corrosion resistance of
biomedical Mg.
PMID- 27615738
TI - Chemical constituents from the roots of Ampelopsis delavayana and their
antibacterial activities.
AB - Two new aromatic glycosides, 2-methylphenyl O-beta-d-xylopyranosyl-(1->6)-O-beta
d-glucopyranoside (1) and 2-methylphenyl O-alpha-arabinofuranosyl-(1->6)-O-beta
glucopyranoside (2), together with eight known compounds were isolated from the
roots of Ampelopsis delavayana. Their structures were elucidated on the basis of
extensive spectroscopic analysis. Furthermore, the in vitro antibacterial
activities of 1 and 2 were investigated using serial twofold dilution in three
bacteria including Escherichia coli, Pseudomonas aeruginosa and Staphylococcus
aureus.
PMID- 27615739
TI - Combined Tumor- and Neovascular-"Dual Targeting" Gene/Chemo-Therapy Suppresses
Tumor Growth and Angiogenesis.
AB - A rational combination is critical to achieve efficiently synergistic therapeutic
efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T
NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with
antiangiogenesis/antitumor agents. The truncated bFGF peptide (tbFGF), which
could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial
cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs)
simultaneously loaded with PEDF gene and paclitaxel in this study. The obtained T
NPs with better pharmaceutical properties had elevated cytotoxicity and enhanced
expression of PEDF and alpha-tubulin on FGFR1-overexpressing cells. The uptake of
T-NPs increased in C26 cells, probably mediated by tbFGF via specific
recognization of the overexpressed FGFR1. T-NPs dramatically disrupted the tube
formation of primary human umbilical vein endothelial cells (HUVECs) and
displayed improved antiangiogenic activity in the transgenic zebrafish model and
the alginate-encapsulated tumor cell model. More importantly, T-NPs achieved a
markedly higher antitumor efficacy in the C26 tumor-bearing mice model. The
antitumor effect involved the inhibition of tumor cell proliferation and
angiogenesis, induction of apoptosis, and down-regulation of FGFR1. The enhanced
antitumor activity of T-NPs probably resulted from the raised distribution in
tumor tissues. In addition, T-NPs had no obvious toxicity as evaluated by weight
monitoring, serological/biochemical analyses, and H&E staining. These results
revealed that T-NPs, an active targeting gene/chemo-therapy, indeed had superior
antitumor efficacy and negligible side effect, suggesting that this novel
combination is a potential tumor therapy and a new treatment strategy and that
the tbFGF modified nanoparticles could be applied to a wide range of tumor
genetic therapies and/or tumor-chemical therapies.
PMID- 27615740
TI - Localization of cortical primary motor area of the hand using navigated
transcranial magnetic stimulation, BOLD and arterial spin labeling fMRI.
AB - BACKGROUND: Although the relationship between neuronavigated transcranial
magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has
been widely studied in motor mapping, it is unknown how the motor response type
or the choice of motor task affect this relationship. NEW METHOD: Centers of
gravity (CoGs) and response maxima were measured with blood-oxygen-level
dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against
nTMS CoGs and response maxima, which were mapped with motor evoked potentials
(MEPs) and silent periods (SPs). RESULTS: No differences in motor representations
(CoGs and response maxima) were observed in lateral-medial direction (p=0.265).
fMRI methods localized the motor representation more posterior than nTMS
(p<0.001). This was not affected by the BOLD fMRI motor task (p>0.999) nor nTMS
response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD
fMRI CoGs (p>=0.070), but the ASL CoG was deeper in comparison to other methods
(p<=0.042). The BOLD fMRI motor task did not influence the depth of the motor
representation (p>=0.745). The median Euclidean distances between the nTMS and
fMRI motor representations varied between 7.7mm and 14.5mm and did not differ
between the methods (F<=1.23, p>=0.318). COMPARISON WITH EXISTING METHODS: The
relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP)
responses, and whether the choice of motor task affects this relationship, have
not been studied before. CONCLUSIONS: The congruence between fMRI and nTMS is
good. The choice of nTMS motor response type nor BOLD fMRI motor task had no
effect on this relationship.
PMID- 27615741
TI - Colocalization of synapse marker proteins evaluated by STED-microscopy reveals
patterns of neuronal synapse distribution in vitro.
AB - BACKGROUND: Quantification of synapses and their morphological analysis are
extensively used in network development and connectivity studies, drug screening
and other areas of neuroscience. Thus, a number of quantitative approaches were
introduced so far. However, most of the available methods are highly tailored to
specific applications and have limitations for widespread use. NEW METHOD: We
present a new plugin for the open-source software ImageJ to provide a modifiable,
high-throughput and easy to use method for synaptic puncta analysis. Our approach
is based on colocalization of pre- and postsynaptic protein markers. Structurally
completed glutamatergic and GABAergic synapses were identified by VGLUT1-PSD95
and VGAT-gephyrin colocalization, respectively. By combining conventional
confocal microscopy with stimulated emission depletion (STED) imaging, we propose
a method to quantify the number of scaffolding protein clusters, recruited to a
single postsynaptic density. RESULTS: In a proof-of-concept study, we reveal the
differential distribution of glutamatergic and GABAergic synapse density with
reference to perineuronal net (PNN) expression. Using super-resolution STED
imaging, we demonstrate that postsynaptic puncta of completed synapses are
composed of significantly more protein clusters, compared to uncompleted
synapses. COMPARISON WITH EXISTING METHODS: Our Synapse Counter plugin for ImageJ
offers a rapid and unbiased research tool for a broad spectrum of
neuroscientists. The proposed method of synaptic protein clusters quantification
exploits super-resolution imaging to provide a comprehensive approach to the
analysis of postsynaptic density composition. CONCLUSIONS: Our results strongly
substantiate the benefits of colocalization-based synapse detection.
PMID- 27615742
TI - PEG-fibrinogen hydrogels for three-dimensional breast cancer cell culture.
AB - Tissue-engineered three-dimensional (3D) cancer models employing biomimetic
hydrogels as cellular scaffolds provide contextual in vitro recapitulation of the
native tumor microenvironment, thereby improving their relevance for use in
cancer research. This study reports the use of poly(ethylene glycol)-fibrinogen
(PF) as a suitable biosynthetic hydrogel for the 3D culture of three breast
cancer cell lines: MCF7, SK-BR-3, and MDA-MB-231. Modification of the matrix
characteristics of PF hydrogels was achieved by addition of excess poly(ethylene
glycol) diacrylate, which resulted in differences in Young's moduli, degradation
behavior, release kinetics, and ultrastructural variations in scaffold
microarchitecture. Cancer cells were maintained in 3D culture with high viability
within these hydrogels and resulted in cell-type dependent morphological changes
over time. Cell proliferation and 3D morphology within the hydrogels were
visualized through immunofluorescence staining. Finally, spatial heterogeneity of
colony area within the hydrogels was quantified, with peripheral cells forming
colonies of higher area compared to those in the interior regions. Overall, PF
based hydrogels facilitate 3D culture of breast cancer cells and investigation of
cellular behavior in response to varying matrix characteristics. PF-based cancer
models could be potentially used in future investigations of cancer biology and
in anti-cancer drug-testing applications. (c) 2016 Wiley Periodicals, Inc. J
Biomed Mater Res Part A: 105A: 236-252, 2017.
PMID- 27615743
TI - The role of exopolymeric substances in the bioaccumulation and toxicity of Ag
nanoparticles to algae.
AB - Exopolymeric substances (EPS) have an important role in bioaccumulation and
toxicity of nanoparticles (NPs) to algae, which warrants specific studies. The
interaction of EPS with citrate and polyvinyl pyrrolidone (PVP) coated AgNPs (C
AgNPs and P-AgNPs, respectively) and its roles in bioaccumulation and toxicity of
the AgNPs to Chlorella pyrenoidosa were investigated. The amino and aromatic
carboxylic groups in the EPS were involved in the EPS-AgNP interactions. Compared
with Ag(+), C-AgNPs had comparable total bioaccumulation but greater absorption
by intact algae with EPS; P-AgNPs had the smallest total bioaccumulation and were
mainly adsorbed on algal surfaces. With EPS removed, the total bioaccumulations
and surface adsorptions for the three Ag species decreased but the cell
internalizations increased; the 96 h half growth inhibition concentrations
decreased, indicating EPS alleviated the algal toxicity of Ag. The cell
internalized but not the adsorbed AgNPs could contribute to the nanotoxicity. The
EPS could bind both AgNPs and Ag(+), and thus inhibited the cell internalization
and the nanotoxicity. However, the EPS-bound Ag on the cell surfaces would
migrate along with the algae and be biologically amplified in the aquatic food
chains, presenting ecological risks. These results are helpful for understanding
the fate and ecological effects of NPs.
PMID- 27615744
TI - The RNA-binding protein LARP4 regulates cancer cell migration and invasion.
AB - LARP4 is a La-related RNA-binding protein implicated in regulating mRNA
translation, which interacts with poly(A)-binding protein (PABP). We previously
identified LARP4 in an RNAi screen as one of several genes that regulate the
shape of PC3 prostate cancer cells. Here we show that LARP4 depletion induces
cell elongation in PC3 cells and MDA-MB-231 breast cancer cells. LARP4 depletion
increases cell migration and invasion, as well as inducing invasive cell
protrusions in 3D Matrigel. Conversely, LARP4 over-expression reduces cell
elongation and increases cell circularity. LARP4 mutations are found in a variety
of cancers. Introduction of some of these cancer-associated mutations, including
a truncation mutant, into LARP4 enhances its effects on cell morphology. The
truncation mutant shows enhanced interaction with PABP. We propose that LARP4
inhibits migration and invasion of cancer cells, and that some cancer-associated
mutations stimulate these effects of LARP4. (c) 2016 The Authors. Cytoskeleton
Published by Wiley Periodicals, Inc.
PMID- 27615791
TI - Rapid Onset of Hypomania Associated with Transcranial Direct Current Stimulation
in a Patient with Bipolar Depression.
PMID- 27615746
TI - Temperature-Responsive Nanofibrillar Hydrogels for Cell Encapsulation.
AB - Natural extracellular matrices often have a filamentous nature, however, only a
limited number of artificial extracellular matrices have been designed from
nanofibrillar building blocks. Here we report the preparation of temperature
responsive nanofibrillar hydrogels from rod-shaped cellulose nanocrystals (CNCs)
functionalized with a copolymer of N-isopropylacrylamide and N,N'
dimethylaminoethyl methacrylate. The composition of the copolymer was tuned to
achieve gelation of the suspension of copolymer-functionalized CNCs at 37
degrees C in cell culture medium and gel dissociation upon cooling it to room
temperature. The mechanical properties and the structure of the hydrogel were
controlled by changing copolymer composition and the CNC-to-copolymer mass ratio.
The thermoreversible gels were used for the encapsulation and culture of
fibroblasts and T cells and showed low cytotoxicity. Following cell culture, the
cells were released from the gel by reducing the temperature, thus, enabling
further cell characterization. These results pave the way for the generation of
injectable temperature-responsive nanofibrillar hydrogels. The release of cells
following their culture in the hydrogels would enable enhanced cell
characterization and potential transfer in a different cell culture medium.
PMID- 27615745
TI - Risk factors for hospital re-presentation among older adults following fragility
fractures: a systematic review and meta-analysis.
AB - BACKGROUND: Older adults hospitalized with fragility fractures are at high risk
of negative events that can culminate in re-presentations to hospital emergency
departments or readmissions to hospital. This systematic review aimed to identify
patient, clinical, or hospital-related factors that are identifiable at the index
admission and that may be associated with re-presentations to hospital emergency
departments or hospital readmissions in older adults following fragility
fractures. METHODS: Four electronic databases (PubMed, CINAHL, Embase, and
Scopus) were searched. A suite of search terms identified peer-reviewed English
language articles that examined potential correlates of hospital re-presentation
in older adults (mean age >= 65 years) who were discharged from hospital
following treatment for fragility fractures. A three-stage screening process
(titles, abstracts, full text) was conducted by two researchers independently.
Participant characteristics, study design, potential correlates examined,
analyses, and findings were extracted for studies included in the review. Quality
and risk of bias were assessed with the Effective Public Health Practice Project
Quality Assessment Tool. The strength of evidence was incorporated into a best
evidence synthesis, and meta-analysis was conducted where effect pooling was
possible. RESULTS: Eleven of 35 eligible studies were categorized as high quality
studies. These studies reported that age, higher Cumulative Illness Rating
scores, American Society of Anesthesiologists scores > 3, longer length of stay,
male sex, cardiovascular disease, low post-operative hemoglobin, kidney disease,
dementia and cancer were factors identified at the index admission that were
predictive of subsequent re-presentation to hospital. Age was the only predictor
for which pooling of effects across studies was possible: pooling was conducted
for re-presentation <= 30 days (pooled OR, 1.27; 95 % CI, 1.14-1.43) and > 30
days (pooled OR, 1.23; 95 % CI, 1.01-1.50). CONCLUSIONS: The best-evidence
synthesis, in addition to the meta-analysis, identified a range of factors that
may have utility in guiding clinical practice and policy guidelines for targeted
interventions to reduce the need for re-presentation to hospital among this frail
clinical population. The paucity of studies investigating re-presentations to
hospital emergency departments without admission was an important gap in the
literature identified in this review. Key limitations were exclusion of non
English language studies and grey literature. SYSTEMATIC REVIEW REGISTRATION:
PROSPERO CRD42015019379 .
PMID- 27615792
TI - Modulation of the Direction and Magnitude of Hebbian Plasticity in Human Motor
Cortex by Stimulus Intensity and Concurrent Inhibition.
AB - BACKGROUND: The mechanisms mediating the efficacy and variability of paired
associative stimulation (PAS), thought to be mediated by Hebbian plasticity,
remain incompletely understood. The magnitude and direction of Hebbian plasticity
may be modulated by the level of neural depolarisation, which is influenced by
stimulation intensity and interactions with cortical circuits. HYPOTHESIS: PAS
effects would be influenced by the intensity of transcranial magnetic stimulation
(TMS) and interaction with other circuits. In particular, PAS would be inhibited
by concurrent inhibitory input following median nerve stimulation, known as short
latency afferent inhibition (SAI). METHODS: PAS was tested at an interstimulus
interval (ISI) 2 ms or 6 ms longer than the N20 peak of the median nerve
somatosensory-evoked potential (PASN20+2, PASN20+6). PASN20+2 was tested at three
different TMS intensities. Short interval intracortical facilitation and
inhibition were tested in the presence of SAI (SICFSAI, SICISAI). RESULTS: The
propensity for long term potentiation like effects increased with higher PASN20+2
TMS stimulus intensity, whereas long term depression like effects ensued at
subthreshold intensity. Stronger SAI correlated with weaker PAS LTP-like effects
across individuals. PASN20+2 (maximal SAI) was less effective than PASN20+6 (weak
SAI). SICFSAI or SICISAI did not influence PAS response. CONCLUSION: Inter
individual differences in SAI contribute to the variability in PAS efficacy. The
magnitude and direction of PAS effects is modulated by TMS intensity. Together,
these findings indicate that the level of neural activity induced by stimulation
likely plays a crucial role in determining the direction and magnitude of Hebbian
plastic effects evoked by PAS in human cortex.
PMID- 27615793
TI - Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in
Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.
AB - BACKGROUND: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may
improve negative symptoms in patients with schizophrenia, but few studies have
investigated the underlying neural mechanism. OBJECTIVE: This study aims to
investigate changes in the levels of glutamate and glutamine (Glx,
neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left
dorsolateral prefrontal cortex of patients with schizophrenia treated with active
bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1H-Magnetic
Resonance Spectroscopy (1H-MRS). METHODS: Patients were randomized to a 3-week
course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1H
MRS data were available for 24 patients with schizophrenia with moderate to
severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative
subscale >= 15). Absolute metabolite concentrations were calculated using LCModel
with the water peak as reference. To explore the association between treatment
condition and changes in concentration of Glx and NAA, we applied a linear
regression model. RESULTS: We observed an increase of Glx concentration in the
active treatment group and a decrease of Glx concentration in the group receiving
sham treatment. The association between changes in Glx concentration and
treatment condition was significant. No significant associations between changes
in NAA and treatment condition were found. CONCLUSIONS: Noninvasive
neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx
concentration in the prefrontal cortex of patients with schizophrenia. Larger
studies are needed to confirm these findings and further elucidate the underlying
neural working mechanism of rTMS.
PMID- 27615794
TI - Arabidopsis Root-Type Ferredoxin:NADP(H) Oxidoreductase 2 is Involved in
Detoxification of Nitrite in Roots.
AB - Ferredoxin:NADP(H) oxidoreductase (FNR) plays a key role in redox metabolism in
plastids. Whereas leaf FNR (LFNR) is required for photosynthesis, root FNR (RFNR)
is believed to provide electrons to ferredoxin (Fd)-dependent enzymes, including
nitrite reductase (NiR) and Fd-glutamine-oxoglutarate aminotransferase (Fd-GOGAT)
in non-photosynthetic conditions. In some herbal species, however, most nitrate
reductase activity is located in photosynthetic organs, and ammonium in roots is
assimilated mainly by Fd-independent NADH-GOGAT. Therefore, RFNR might have a
limited impact on N assimilation in roots grown with nitrate or ammonium nitrogen
sources. AtRFNR genes are rapidly induced by application of toxic nitrite. Thus,
we tested the hypothesis that RFNR could contribute to nitrite reduction in roots
by comparing Arabidopsis thaliana seedlings of the wild type with loss-of
function mutants of RFNR2 When these seedlings were grown under nitrate, nitrite
or ammonium, only nitrite nutrition caused impaired growth and nitrite
accumulation in roots of rfnr2 Supplementation of nitrite with nitrate or
ammonium as N sources did not restore the root growth in rfnr2 Also, a scavenger
for nitric oxide (NO) could not effectively rescue the growth impairment. Thus,
nitrite toxicity, rather than N depletion or nitrite-dependent NO production,
probably causes the rfnr2 root growth defect. Our results strongly suggest that
RFNR2 has a major role in reduction of toxic nitrite in roots. A specific set of
genes related to nitrite reduction and the supply of reducing power responded to
nitrite concomitantly, suggesting that the products of these genes act co
operatively with RFNR2 to reduce nitrite in roots.
PMID- 27615795
TI - Sulfoquinovosyldiacylglycerol has an Essential Role in Thermosynechococcus
elongatus BP-1 Under Phosphate-Deficient Conditions.
AB - Anionic lipids, sulfoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol
(PG), are major classes of the thylakoid membrane lipids in cyanobacteria and
plant chloroplasts. PG is essential for growth and photosynthesis of
cyanobacteria, algae and plants, but the requirement for SQDG differs even among
cyanobacterial species. Although SQDG and PG can compensate each other in part
presumably to maintain proper balance of anionic charge in lipid bilayers, the
functional relationship of these lipids is largely unknown. In this study, we
inactivated the sqdB gene, encoding a UDP-sulfoquinovose synthase and involved in
SQDG biosynthesis, in Thermosynechococcus elongatus BP-1. In wild-type cells, PG
accounted for only approximately 3.5 mol% of total membrane lipids, but its
content was substantially increased along with complete loss of SQDG in the sqdB
mutant. Under phosphate (Pi)-sufficient conditions, the growth rate and PSII
activity were slightly lower in sqdB than in wild-type cells. In addition, the
formation of PSI trimers and PSII dimers and energy transfer in phycobilisomes
were perturbed in the mutant. Under Pi-deficient conditions, the growth of sqdB
cells was severely impaired, with a decrease in PSII activity. PG supplementation
could partially rescue the defective growth and PSII activity of Pi-deficient
sqdB cells but fully recovered the impaired growth of the pgsA mutant of T.
elongatus, which is deficient in PG biosynthesis. These data suggest that SQDG
has a specific role in the growth and photosynthesis of T. elongatus, which
cannot be complemented by PG, particularly under Pi-deficient conditions.
PMID- 27615796
TI - Two Members of the Aluminum-Activated Malate Transporter Family, SlALMT4 and
SlALMT5, are Expressed during Fruit Development, and the Overexpression of
SlALMT5 Alters Organic Acid Contents in Seeds in Tomato (Solanum lycopersicum).
AB - The aluminum-activated malate transporter (ALMT) family of proteins transports
malate and/or inorganic anions across plant membranes. To demonstrate the
possible role of ALMT genes in tomato fruit development, we focused on SlALMT4
and SlALMT5, the two major genes expressed during fruit development. Predicted
proteins were classified into clade 2 of the family, many members of which
localize to endomembranes. Tissue-specific gene expression was determined using
transgenic tomato expressing the beta-glucuronidase reporter gene controlled by
their own promoters. Both the genes were expressed in vascular bundles connecting
to developing seeds in fruit and in the embryo of mature seeds. Further, SlALMT5
was expressed in embryo in developing seeds in fruit. Subcellular localization of
both proteins to the endoplasmic reticulum (ER) was established by transiently
expressing the green fluorescent protein fusions in plant protoplasts. SlALMT5
probably localized to other endomembranes as well. Localization of SlALMT5 to the
ER was also confirmed by immunoblot analysis. The transport function of both
SlALMT proteins was investigated electrophysiologically in Xenopus oocytes.
SlALMT5 transported malate and inorganic anions such as nitrate and chloride, but
not citrate. SlALMT4 also transported malate, but the results were less
consistent perhaps because it did not localize strongly to the plasma membrane.
To elucidate the physiological role of SlALMT5 further, we overexpressed SlALMT5
in tomato. Compared with the wild type, overexpressors exhibited higher malate
and citrate contents in mature seeds, but not in fruit. We conclude that the
malate transport function of SlALMT5 expressed in developing fruit influences the
organic acid contents in mature seeds.
PMID- 27615798
TI - Recent trends in disease severity and quality of life instruments for patients
with atopic dermatitis: A systematic review.
AB - BACKGROUND: A significant number of instruments exist that are aimed at
quantifying atopic dermatitis (AD) outcomes. OBJECTIVE: We sought to assess
recent trends in the use of disease severity and quality of life (QOL) outcome
instruments in randomized controlled trials (RCTs) conducted on patients with AD
between July 2010 and July 2015. METHODS: A total of 540 nonduplicate records
were identified through searches of Scopus and Ovid MEDLINE. Included studies
were RCTs conducted on humans with AD that were published in English between July
2010 and July 2015 and that reported the results of disease severity or QOL
outcome measures. RESULTS: All of the 135 included studies assessed disease
severity. Only 45 studies assessed QOL. Sixty-two disease severity measures and
28 QOL scales were identified. LIMITATIONS: This study was limited by its
timeframe of 5 years and by the exclusion of non-RCTs and gray literature.
CONCLUSION: Disease severity and QOL outcome measures are instrumental in
evaluating AD treatment efficacy. The number of such tools used in RCTs on
patients with AD continues to rise. Standardization of outcomes instruments is
essential for comparability among studies and improved quality of evidence.
PMID- 27615799
TI - Progressive interatrial block associated with atrial fibrillation in a patient
with hypertrophic cardiomyopathy.
AB - Progressive interatrial block is a clinically significant condition that has
previously been reported in various patient populations. It is a manifestation of
progressive fibrosis affecting the Bachmann region. This report presents a case
of progressive interatrial block associated with atrial fibrillation in the
context of hypertrophic cardiomyopathy.
PMID- 27615797
TI - Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to
viviparity.
AB - We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc)
modification of histone H2A at Ser(40) (H2AS40Gc). The mouse genome contains 18
H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). The
combination of production of monoclonal antibody and mass spectrometric analyses
with reverse-phase (RP)-high performance liquid chromatography (HPLC)
fractionation indicated that the O-GlcNAcylation is specific to the Ser(40)
isoforms. The H2AS40Gc site is in the L1 loop structure where two H2A molecules
interact in the nucleosome. Targets of H2AS40Gc are distributed genome-wide and
are dramatically changed during the process of differentiation in mouse
trophoblast stem cells. In addition to the mouse, H2AS40Gc was also detected in
humans, macaques and cows, whereas non-mammalian species possessing only the
Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal.
Genome database surveys revealed that Ser(40) isoforms of H2A emerged in
Marsupialia and persisted thereafter in mammals. We propose that the emergence of
H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide
epigenetic events that correlate with the evolution of placental animals.
PMID- 27615801
TI - Colorimetric aptasensor for progesterone detection based on surfactant-induced
aggregation of gold nanoparticles.
AB - This paper proposes an aptasensor for progesterone (P4) detection in human serum
and urine based on the aggregating behavior of gold nanoparticles (AuNPs)
controlled by the interactions among P4-binding aptamer, target P4 and cationic
surfactant hexadecyltrimethylammonium bromide (CTAB). The aptamer can form an
aptamer-P4 complex with P4, leaving CTAB free to aggregate AuNPs in this
aptasensor. Thus, the sensing solution will turn from red (520 nm) to blue (650
nm) in the presence of P4 because P4 aptamers are used up firstly owing to the
formation of an aptamer-P4 complex, leaving CTAB free to aggregate AuNPs.
However, in the absence of P4, CTAB combines with aptamers so that AuNPs still
remain dispersed. Therefore, this assay makes it possible to detect P4 not only
by absorbance measurement but also through naked eyes. By monitoring the
variation of absorbance and color, a CTAB-induced colorimetric assay for P4
detection was established with a detection limit of 0.89 nM. Besides, the
absorbance ratio A650/A520 has a linear correlation with the P4 concentration of
0.89-500 nM. Due to the excellent recoveries in serum and urine, this biosensor
has great potential with respect to the visual and instrumental detection of P4
in biological fluids.
PMID- 27615802
TI - Anisotropic Magnetite Nanorods for Enhanced Magnetic Hyperthermia.
AB - There is an increasing need for new strategies to improve the heating efficiency
or the specific absorption rate (SAR) of magnetite (Fe3 O4 ), which is the only
FDA approved magnetic material. We propose a facile approach to obtain well
dispersed highly crystalline Fe3 O4 nanorods (NRs) by the reduction of beta-FeOOH
in an organic solvent and demonstrate that the SAR of Fe3 O4 NRs can be enhanced
by tuning their aspect ratios. Fe3 O4 NRs with an aspect ratio of 4.5 have a much
higher SAR as compared with 15 nm Fe3 O4 nanoparticles and Fe3 O4 NRs
counterparts with an aspect ratio of 10. The highest SAR is greatly increased up
to 1072 W g-1 for an ac field of 33 kA m-1 and a concentration of 5 mg mL-1 ,
which is mostly attributed to hysteresis losses. These findings pave a new
pathway for the design and synthesis of novel anisotropic iron oxide
nanostructures with an optimal heating efficiency for advanced hyperthermia.
PMID- 27615800
TI - Akting up in the GABA hypothesis of schizophrenia: Akt1 deficiency modulates
GABAergic functions and hippocampus-dependent functions.
AB - Accumulating evidence implies that both AKT1 and GABAA receptor (GABAAR) subunit
genes are involved in schizophrenia pathogenesis. Activated Akt promotes
GABAergic neuron differentiation and increases GABAAR expression on the plasma
membrane. To elucidate the role of Akt1 in modulating GABAergic functions and
schizophrenia-related cognitive deficits, a set of 6 in vitro and in vivo
experiments was conducted. First, an Akt1/2 inhibitor was applied to evaluate its
effect on GABAergic neuron-like cell formation from P19 cells. Inhibiting Akt
resulted in a reduction in parvalbumin-positive neuron-like cells. In Akt1(-/-)
and wild-type mice, seizures induced using pentylenetetrazol (a GABAAR
antagonist) were measured, and GABAAR expression and GABAergic interneuron
abundance in the brain were examined. Female Akt1(-/-) mice, but not male Akt1(-/
) mice, exhibited less pentylenetetrazol-induced convulsive activity than their
corresponding wild-type controls. Reduced parvalbumin-positive interneuron
abundance and GABAAR subunit expression, especially in the hippocampus, were also
observed in female Akt1(-/-) mice compared to female wild-type mice.
Neuromorphometric analyses revealed significantly reduced neurite complexity in
hippocampal pyramidal neurons. Additionally, female Akt1(-/-) mice displayed
increased hippocampal oscillation power and impaired spatial memory compared to
female wild-type mice. Our findings suggest that Akt1 deficiency modulates
GABAergic interneurons and GABAAR expression, contributing to hippocampus
dependent cognitive functional impairment.
PMID- 27615803
TI - Body length rather than routine metabolic rate and body condition correlates with
activity and risk-taking in juvenile zebrafish Danio rerio.
AB - In this study, the following hypotheses were explored using zebrafish Danio
rerio: (1) individuals from the same cohort differ consistently in activity and
risk-taking and (2) variation in activity and risk-taking is linked to individual
differences in metabolic rate, body length and body condition. To examine these
hypotheses, juvenile D. rerio were tested for routine metabolic rate and
subsequently exposed to an open field test. Strong evidence was found for
consistent among-individual differences in activity and risk-taking, which were
overall negatively correlated with body length, i.e. larger D. rerio were found
to be less active in a potentially dangerous open field and a similar trend was
found with respect to a more direct measure of their risk-taking tendency. In
contrast, routine metabolic rate and body condition were uncorrelated with both
activity and risk-taking of juvenile D. rerio. These findings suggest that body
length is associated with risk-related behaviours in juvenile D. rerio for which
larger, rather than smaller, individuals may have a higher risk of predation,
while the role for routine metabolic rate is relatively limited or non-existent,
at least under the conditions of the present study.
PMID- 27615804
TI - The Socio-Temporal Brain: Connecting People in Time.
AB - Temporal and social processing are intricately linked. The temporal extent and
organization of interactional behaviors both within and between individuals
critically determine interaction success. Conversely, social signals and social
context influence time perception by, for example, altering subjective duration
and making an event seem 'out of sync'. An 'internal clock' involving
subcortically orchestrated cortical oscillations that represent temporal
information, such as duration and rhythm, as well as insular projections linking
temporal information with internal and external experiences is proposed as the
core of these reciprocal interactions. The timing of social relative to non
social stimuli augments right insular activity and recruits right superior
temporal cortex. Together, these reciprocal pathways may enable the exchange and
respective modulation of temporal and social computations.
PMID- 27615805
TI - 'What' Is Happening in the Dorsal Visual Pathway.
AB - The cortical visual system is almost universally thought to be segregated into
two anatomically and functionally distinct pathways: a ventral occipitotemporal
pathway that subserves object perception, and a dorsal occipitoparietal pathway
that subserves object localization and visually guided action. Accumulating
evidence from both human and non-human primate studies, however, challenges this
binary distinction and suggests that regions in the dorsal pathway contain object
representations that are independent of those in ventral cortex and that play a
functional role in object perception. We review here the evidence implicating
dorsal object representations, and we propose an account of the anatomical
organization, functional contributions, and origins of these representations in
the service of perception.
PMID- 27615806
TI - Biocompatible Stimuli-Responsive W/O/W Multiple Emulsions Prepared by One-Step
Mixing with a Single Diblock Copolymer Emulsifier.
AB - Multiple water-in-oil-in-water (W/O/W) emulsions are promising materials in
designing carriers of hydrophilic molecules or drug delivery systems, provided
stability issues are solved and biocompatible chemicals can be used. In this
work, we designed a biocompatible amphiphilic copolymer, poly(dimethylsiloxane)-b
poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAEMA), that can stabilize
emulsions made with various biocompatible oils. The hydrophilic/hydrophobic
properties of the copolymer can be adjusted using both pH and ionic strength
stimuli. Consequently, the making of O/W (oil in water), W/O (water in oil), and
W/O/W emulsions can be achieved by sweeping the pH and ionic strength. Of
importance, W/O/W emulsions are formulated over a large pH and ionic strength
domain in a one-step emulsification process via transitional phase inversion and
are stable for several months. Cryo-TEM and interfacial tension studies show that
the formation of these W/O/W emulsions is likely to be correlated to the
interfacial film curvature and microemulsion morphology.
PMID- 27615807
TI - Physical soil architectural traits are functionally linked to carbon
decomposition and bacterial diversity.
AB - Aggregates play a key role in protecting soil organic carbon (SOC) from microbial
decomposition. The objectives of this study were to investigate the influence of
pore geometry on the organic carbon decomposition rate and bacterial diversity in
both macro- (250-2000 MUm) and micro-aggregates (53-250 MUm) using field samples.
Four sites of contrasting land use on Alfisols (i.e. native pasture, crop/pasture
rotation, woodland) were investigated. 3D Pore geometry of the micro-aggregates
and macro-aggregates were examined by X-ray computed tomography (MUCT). The
occluded particulate organic carbon (oPOC) of aggregates was measured by size and
density fractionation methods. Micro-aggregates had 54% less MUCT observed
porosity but 64% more oPOC compared with macro-aggregates. In addition, the pore
connectivity in micro-aggregates was lower than macro-aggregates. Despite both
lower MUCT observed porosity and pore connectivity in micro-aggregates, the
organic carbon decomposition rate constant (Ksoc) was similar in both aggregate
size ranges. Structural equation modelling showed a strong positive relationship
of the concentration of oPOC with bacterial diversity in aggregates. We use these
findings to propose a conceptual model that illustrates the dynamic links between
substrate, bacterial diversity, and pore geometry that suggests a structural
explanation for differences in bacterial diversity across aggregate sizes.
PMID- 27615808
TI - Orbital Angular Momentum-based Space Division Multiplexing for High-capacity
Underwater Optical Communications.
AB - To increase system capacity of underwater optical communications, we employ the
spatial domain to simultaneously transmit multiple orthogonal spatial beams, each
carrying an independent data channel. In this paper, we show up to a 40-Gbit/s
link by multiplexing and transmitting four green orbital angular momentum (OAM)
beams through a single aperture. Moreover, we investigate the degrading effects
of scattering/turbidity, water current, and thermal gradient-induced turbulence,
and we find that thermal gradients cause the most distortions and turbidity
causes the most loss. We show systems results using two different data generation
techniques, one at 1064 nm for 10-Gbit/s/beam and one at 520 nm for 1
Gbit/s/beam; we use both techniques since present data-modulation technologies
are faster for infrared (IR) than for green. For the 40-Gbit/s link, data is
modulated in the IR, and OAM imprinting is performed in the green using a
specially-designed metasurface phase mask. For the 4-Gbit/s link, a green laser
diode is directly modulated. Finally, we show that inter-channel crosstalk
induced by thermal gradients can be mitigated using multi-channel equalisation
processing.
PMID- 27615809
TI - Reliability and refinement of a pain location tool for children's abdominal
surgery.
AB - AIM: To determine the 'inter-rater' and test-retest reliability of a pain
location tool for children. MATERIALS & METHODS: In children aged 5-14 years who
had undergone a laparoscopic operation, pain scores at each of seven abdominal
locations, and at the shoulder tip, were recorded at baseline and after a 5- and
30-min interval. RESULTS: Intraclass correlation coefficients were predominantly
in the 'moderate' to 'substantial' range for both 'inter-rater' and test-retest
reliability. Three quarters of children would prefer an electronic version of the
tool. Thematic analysis showed accuracy, usability, utility and usefulness were
areas for future development. CONCLUSION: Children can reliably indicate where
they hurt after laparoscopic surgery. An electronic version could increase
acceptability to children and usability by professionals.
PMID- 27615812
TI - A taxonomic review of the genus Antepipona de Saussure, 1855 (Hymenoptera:
Vespidae: Eumeninae) from India.
AB - A review of 20 Indian species of the genus Antepipona de Saussure with a key to
species and subspecies is provided. A new synonymy is proposed for Antepipona
biguttata (Fabricius, 1787) =A. excelsa keralensis Lambert, 2004, syn. nov. The
parasitic association of Strepsiptera is reported for the first time in the genus
Antepipona. Antepipona rufescens (Smith, 1857) is newly recorded from India and
A. ovalis (de Saussure, 1853) from Bangladesh. The reported distributions of ten
species within India are enlarged.
PMID- 27615811
TI - Epidemiology and Immediate Indirect Effects of Respiratory Viruses in Lung
Transplant Recipients: A 5-Year Prospective Study.
AB - The epidemiology of respiratory viruses (RVs) in lung transplant recipients
(LTRs) and the relationship of RVs to lung function, acute rejection (AR) and
opportunistic infections in these patients are not well known. We performed a
prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPSs)
from asymptomatic LTRs during seasonal changes and from LTRs with upper
respiratory tract infectious disease (URTID), lower respiratory tract infectious
disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain
reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6%
positivity rate and mean follow-up of 3.4 years (interquartile range 2.5-4.0
years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis
cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused
mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%).
In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3
mo (p = 0.04). In a nested case-control analysis, AR was associated with RVs
(hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR
8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID
(HR 2.53) in the previous 3 mo. There was no association between RVs and
Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we
documented a high incidence of RV infections in LTRs. LRTID produced significant
lung function abnormalities. Associations were observed between AR and RVs,
between P. aeruginosa colonization or infection and LRTID, and between CMV
replication or disease and URTID.
PMID- 27615810
TI - Visualization and ligand-induced modulation of dopamine receptor dimerization at
the single molecule level.
AB - G protein-coupled receptors (GPCRs), including dopamine receptors, represent a
group of important pharmacological targets. An increased formation of dopamine
receptor D2 homodimers has been suggested to be associated with the
pathophysiology of schizophrenia. Selective labeling and ligand-induced
modulation of dimerization may therefore allow the investigation of the
pathophysiological role of these dimers. Using TIRF microscopy at the single
molecule level, transient formation of homodimers of dopamine receptors in the
membrane of stably transfected CHO cells has been observed. The equilibrium
between dimers and monomers was modulated by the binding of ligands; whereas
antagonists showed a ratio that was identical to that of unliganded receptors,
agonist-bound D2 receptor-ligand complexes resulted in an increase in
dimerization. Addition of bivalent D2 receptor ligands also resulted in a large
increase in D2 receptor dimers. A physical interaction between the protomers was
confirmed using high resolution cryogenic localization microscopy, with ca. 9 nm
between the centers of mass.
PMID- 27615813
TI - Potamotrygon rex, a new species of Neotropical freshwater stingray
(Chondrichthyes: Potamotrygonidae) from the middle and upper rio Tocantins,
Brazil, closely allied to Potamotrygon henlei (Castelnau, 1855).
AB - A systematic revision of the rio Tocantins stingrays has confirmed the occurrence
of a new species of Potamotrygon first discovered more than two decades ago but
which lacked material for a thorough description. Field surveys since undertaken
in the middle and upper rio Tocantins have assembled significant material that
forms the basis of an ongoing revision of the diverse Tocantins potamotrygonid
assemblage. Potamotrygon rex, sp. nov., is a very large, "black stingray" species
from the mid and upper rio Tocantins that is closely related to P. henlei
(Castelnau), which occurs in the lower Tocantins basin and in rio Araguaia; both
species do not co-occur. Potamotrygon rex, sp. nov., has a unique blackish to
dark brown dorsal color with numerous small, yellow to orange irregular spots
usually forming distinct clusters on dorsal disc, with ocelli in center of
clusters on posterior and outer disc, dorsal tail also with clusters but lateral
tail with ocelli, and a dark brownish to gray color covering most of ventral
surface except nasoral region, gill slits and anterior snout in some specimens,
with small whitish spots on ventral disc, pelvic fins and tail. Potamotrygon rex,
sp. nov., can be further distinguished by its broad pelvic-fin apices, lack of
labial grooves, irregular double row of dorsal tail thorns, and in having two
angular cartilages associated with each hyomandibula. Potamotrygon rex, sp. nov.,
P. henlei, P. leopoldi Castex & Castello, and another new Potamotrygon species
from the rio Tapajos (in description) form a species-group (the "black
stingrays") occurring in rivers draining the central Brazilian shield,
characterized by their black to dark brown but highly ornate dorsal color, wide
pelvic fins with broadly convex apices, among other features. Potamotrygon rex,
sp. nov., is the 25th species of Potamotrygon, and highlights that
very large new species of fishes still await discovery and description in the
Neotropical region.
PMID- 27615814
TI - New South African species of the genus Idiasta Foerster, 1863 (Hymenoptera:
Braconidae: Alysiinae), with a key to the Afrotropical and Malagasy taxa.
AB - A new species from South Africa, Idiasta iaiaorum sp. nov., is described and
illustrated. A key for determination of the Afrotropical and Malagasy Idiasta
species is provided.
PMID- 27615815
TI - Review of the Asian species of the subgenus Neocheilosia Barkalov (Diptera,
Syrphidae), with description of new species.
AB - The Asian species of the subgenus Neocheilosia are reviewed. A new species
Cheilosia (Neocheilosia) shiranesana Barkalov & Ichige sp. n. is described, and
Cheilosia mutini Barkalov is synonymized with Cheilosia komabaensis Shiraki syn.
n. A listing of the five Asian species of the subgenus,information on their
distribution and an illustrated identification key is provided.
PMID- 27615816
TI - Paraorosius, a new genus of leafhopper (Hemiptera: Cicadellidae:
Deltocephalinae: Opsiini), with description of a new species from the Middle
East.
AB - A new genus, of the leafhopper tribe Opsiini, Paraorosius is proposed to
accommodate Orosius minuicus Dlabola, 1979 and, P. hanii sp. n. from the Kingdom
of Saudi Arabia. A key to the genera of Opsiini of the Arabian Peninsula is
provided.
PMID- 27615817
TI - A new species of elongate unpatterned moray eel of the genus Gymnothorax
(Muraenidae: Muraeninae) from the Bay of Bengal.
AB - An elongate, brown unpatterned moray eel, Gymnothorax indicus sp. nov., is
described based on four specimens collected from the northern Bay of Bengal. The
new species is differentiated from other elongate, unpatterned moray eels in
having the following combination of characters: anus at about mid-point of body,
preanal length 2.0 in total length; snout blunt and short; dorsal fin margin
black, 5 mandibular pores; maxillary teeth uniserial, sharp and depressible,
total vertebrae 194 (MVF: 9-79-194).
PMID- 27615818
TI - ILYA V. ENUSHCHENKO & VIKTOR B. SEMENOV (2016) A review of the genus Gyrophaena
Mannerheim 1830 (Coleoptera: Staphylinidae: Aleocharinae: Gyrophaenina) of the
Caucasus and adjacent territories. Zootaxa, 4126: 301-337.
PMID- 27615819
TI - The goblin spider genus Ischnothyreus (Araneae, Oonopidae) in Java and Sumatra.
AB - The genus Ischnothyreus Simon, 1893 from Java and Sumatra is revised with the
description of seven new species from Java (I. baltenspergerae sp. nov., I. bauri
sp. nov., I. gigeri sp. nov., I. ligulatus sp. nov., I. nentwigorum sp. nov., I.
sigridae sp. nov., I. ujungkulon sp. nov) and eight from Sumatra (I. ascifer sp.
nov., I. concavus sp. nov., I. habeggeri sp. nov., I. haymozi sp. nov., I.
lucidus sp. nov., I. marggii sp. nov., I. microphthalmus sp. nov., I. obscurus
sp. nov.). Furthermore the male of I. serpentinum Saaristo, 2001 is described for
the first time and the female redescribed in detail. Special morphological
features of Ischnothyreus males and females are described and discussed, such as
peculiar trochanter projections, partially fused pedipalp segments, processes on
the cheliceral fang base in males and external and internal genitalic structures
in females. This work is part of the Planetary Biodiversity Inventory (PBI) of
goblin spiders (http://research.amnh.org/oonopidae/)..
PMID- 27615820
TI - Catalogue of snout mites (Acariformes: Bdellidae) of the world.
AB - Bdellidae (Trombidiformes: Prostigmata) are moderate to large sized predatory
mites that inhabit soil, leaves, leaf litter, and intertidal rocks. They are
readily recognized by an elongated, snout-like gnathosoma and by elbowed
pedipalps bearing two (one in Monotrichobdella Baker & Balock) long terminal
setae. Despite being among the first mites ever described, with species described
by Carl Linnaeus, the knowledge about bdellids has never been compiled into a
taxonomic catalogue. Here we present a catalogue listing 278 valid species; for
each species we include distribution information, taxonomic literature, and type
depository institutions. The genus Rigibdella Tseng, 1978 is considered a junior
synonym of Cyta von Heyden, 1826, and Bdellodes Oudemans, 1937 is considered a
junior synonym of Odontoscirus Tohr, 1913. Illustrated keys to subfamilies and
genera are presented, as well as keys to species of each genus.
PMID- 27615821
TI - Scale Morphology and Micro-Structure of Monitor Lizards (Squamata: Varanidae:
Varanus spp.) and their Allies: Implications for Systematics, Ecology, and
Conservation.
AB - We analysed scale morphology and micro-structure from five different body regions
using scanning electron microscopy (SEM) across all nine recognized subgenera of
the monitor lizard genus Varanus including 41 different species investigated. As
far as we are aware, this qualitative visual technique was applied by us for the
first time to most monitor lizard species and probably also to the primary
outgroup and sister species Lanthanotus borneensis. A comprehensive list of 20
scalation characters each with up to seven corresponding character states was
established and defined for the five body regions sampled. For the phylogenetic
approach, parsimony analyses of the resulting morphological data matrix as well
as Bremer and bootstrap support calculations were performed with the software
TNT. Our results demonstrate that a variety of micro-ornamentations (i.e., ultra-
or micro-dermatoglyphics) as seen in various squamate groups is hardly present in
monitor lizards. In several species from six out of nine subgenera, however, we
found a honeycomb-shaped micro-structure of foveate polygons. Two further samples
of Euprepiosaurus Fitzinger, 1843 exhibit each another unique microscopic
structure on the scale surface. Notably, the majority of species showing the
honeycombed ultra-structure inhabit arid habitats in Australia, Africa and the
Middle East. Therefore, it can be inferred that this microscopic scalation
feature, which has also been identified in other desert dwelling lizard species,
is taxonomically and ecologically correlated with a xeric habitat type in
varanids, too. In addition, the systematic affiliation of V. spinulosus, an
endemic monitor lizard species from the Solomon Islands with an extraordinary
scale shape, is discussed in the light of current hypotheses about its
phylogenetic position within the Varanidae. Due to its unique scalation
characteristics, in combination with other morphological evidence, a new
monotypic subgenus, Solomonsaurus subgen. nov., is erected for this enigmatic
monitor lizard species. Furthermore, we propose a taxonomic splitting of the
morphologically and ecologically heterogeneous subgenus Euprepiosaurus comprising
the Pacific or mangrove and the tree monitor lizards, respectively, again based
on the SEM data. Thus, for the members of the highly arboreal V. prasinus species
group erection of a new subgenus, Hapturosaurus subgen. nov., is justified based
on the autapomorphic scale shape in concert with further morphological,
phylogenetic and ecological evidence. In addition, V. reisingeri originally
described as a distinct species is considered conspecific with the wide-spread V.
prasinus due to joint synapormorphic features in the ventral scale micro
structure. Consequently, V. prasinus is (again) rendered polytypic with the taxon
reisingeri being assigned subspecies status here. In conclusion, the established
scalation characters allow discrimination of single species even among closely
related Varanus species, such as the members of the V. indicus species group.
Together with a recently published identification key for Southeast Asian monitor
lizards based on macroscopic phenotypic characters (Koch et al. 2013), the SEM
pictures of the present study may serve as additional references for the
microscopic identification of CITES-relevant monitor lizard skins and products,
respectively.
PMID- 27615822
TI - New records and a new species of bivalve (Mollusca: Bivalvia) from Miocene
hydrocarbon seep deposits, North Island, New Zealand.
AB - Fourteen bivalve taxa belonging to 11 families are present in at least 13 early
to middle Miocene hydrocarbon seep deposits in the East Coast Basin, North
Island, New Zealand. Among these are at least three new species, one of which,
Semeloidea (s. l.) bexhavenensis sp. nov. (Lasaeidae), is described here. New
distribution data are recorded for bivalve species in the families Limidae,
Propeamussiidae, Malleidae and Solemyidae. Additional morphological details of
Gigantidas coseli (Mytilidae) and Pratulum quinarium (Cardiidae) are provided
based upon previously unrecorded internal shell features. Palaeoecological
analysis indicates that bivalves utilized a broad range of modes of life and
niches within the New Zealand Miocene seep environment, and no more than ca. 30%
of these bivalve species were likely to have been obligate to seeps.
PMID- 27615823
TI - Bee (Hymenoptera: Apoidea) and hoverfly (Diptera: Syrphidae) pollinators in
Pannonian habitats of Serbia, with a description of a new Eumerus Meigen species
(Syrphidae).
AB - The diversity of bee (Hymenoptera: Apoidea) and hoverfly (Diptera: Syrphidae)
pollinators from ten localities in Vojvodina, Serbia was surveyed. Among
different types of Pannonian habitat (grasslands, heathland and scrub, woodland
and forest habitats) all localities were categorised as forest and steppe. They
were in protected areas, mostly undisturbed by human activity. Censuses of
pollinators took place from 30 March to 10 October, 2014. We recorded 218
pollinator species; 135 bee species (42 Halictidae; 32 Apidae; 29 Andrenidae; 24
Megachilidae; 7 Colletidae; 1 Melittidae) and 83 species of hoverflies. We
describe a new species of hoverfly, Eumerus pannonicus sp. nov., and compare it
to other similar species. Based on our study, the Special Nature Reserve of
Pasnjaci Velike Droplje is critical for the conservation of this new Eumerus
being only found at this locality-and other species such as Chrysotoxum lineare
(Zetterstedt), which is rare in Europe and protected under Serbian legislation.
The highest numbers of bee species were recorded in the Deliblato and Subotica
sand areas (40 and 32, respectively), while Fruska Gora Mountain and the Vrsac
Mountains harboured the highest number of hoverfly species.
PMID- 27615824
TI - A review of Gonothrombium Feider, 1950 (Actinotrichida: Microtrombidiidae) with
description of a new species from Turkey.
AB - The genus Gonothrombium is reassessed, Gonothrombium oudemansianum (Feider, 1948)
redescribed and Gonothrombium ozkani sp. nov. described. All larvae were obtained
by experimental rearing from field-collected females. A key to species, for
adults and larvae, is provided. The distribution of the genus, hitherto known
from Africa and Romania, is extended to the territory of Turkey.
PMID- 27615825
TI - Maculabatis ambigua sp. nov., a new whipray (Myliobatiformes: Dasyatidae) from
the Western Indian Ocean.
AB - A new whipray, Maculabatis ambigua sp. nov., described from material collected
from the Red Sea and off Zanzibar (Tanzania), is probably more widespread in the
northwestern Indian Ocean. It has been confused with other Indian Ocean whiprays
of the genus Maculabatis (formerly Himantura in part) i.e. M. gerrardi and M.
randalli. Maculabatis ambigua sp. nov. was first distinguished from these species
by molecular analysis, and subsequently by a combination of morphological
characters, i.e. disc shape, coloration, morphometrics and squamation. Molecular
data suggest that it is most closely related to the morphologically similar M.
gerrardi, which occurs further east in the Indian Ocean (Oman to Indonesia) and
North-West Pacific (north to Taiwan). The dorsal disc of M. gerrardi typically
has a full or partial coverage of white spots (usually present at least on the
posterior disc), whereas M. ambigua sp. nov. is plain coloured. Maculabatis
randalli, which occurs in the Persian and Arabian Gulfs, is plain coloured, but
has a longer disc relative to its width, more acute and longer snout, longer head
and larger intergill width, wider internasal distance, and a narrower secondary
denticle band in adults. Maculabatis ambigua sp. nov. is relatively common in the
shallow, soft-sedimentary habitats of the southern Red Sea from where it is taken
as low-value or discarded bycatch of trawl fisheries. It is a medium-sized
whipray with a maximum confirmed size of 840 mm disc width.
PMID- 27615826
TI - Garra sindhi, a new species from the Jebel Samhan Nature Reserve in Oman
(Teleostei: Cyprinidae).
AB - Garra sindhi, new species, is described from Wadi Andhur in the Dhofar province
of the Sultanate of Oman. It is closely related to G. dunsirei and G. smarti, two
other species from the same Omani province. It differs from these species by the
following combination of characters: breast covered by scales, a shallow hump on
back, eyes normally developed and 8-12 gill rakers on the lower limb of the first
gill arch.
PMID- 27615827
TI - Epidaus wangi (Hemiptera: Heteroptera: Reduviidae), a new assassin bug from
Tibet, China.
AB - Epidaus wangi Chen, Zhu, Wang & Cai, sp. nov. (Hemiptera: Heteroptera:
Reduviidae: Harpactorinae) from Tibet, China, is described and illustrated based
on male and female specimens. The new species is morphologically similar to E.
tuberosus Yang, 1940. The new species represents the first record of Epidaus
species from Tibet.
PMID- 27615828
TI - Laccomimus xikrin sp. nov. and new records of other species of Laccomimus Toledo
& Michat, 2015 (Coleoptera: Dytiscidae: Laccophilinae) from Brazil.
AB - The genus Laccomimus Toledo & Michat, 2015 was recently erected for small drop
shape Dytiscidae beetles commonly found in Tropical South America associated with
lentic waters. In the present paper a new species, Laccomimus xikrin sp. nov., is
described and illustrated. New records from Brazil are presented for Laccomimus
alvarengi Toledo & Michat, 2015 from Amazonas state, L. bordoni Toledo & Michat,
2015 from Sao Paulo state and L. variegatus Toledo & Michat, 2015 from Para
state.
PMID- 27615829
TI - Lavellodrilus notosetosus sp. nov. (Annelida, Crassiclitellata, Acanthodrilidae):
a new Mexican earthworm with uncommon characters, revealed by a preliminary
revision of subfamily Acanthodrilinae.
AB - A new acanthodriline earthworm species, Lavellodrilus notosetosus sp. nov., is
described from tropical rain forests of southern Mexico. The new species is
placed within the genus Lavellodrilus by the presence of mesial spermathecal
pores. It is separated from other species of the genus by the dorsal location of
setae cd in most of the body, last hearts in segment 13, first intestinal segment
in 20 and genital setae in segment 12. A preliminary morphological revision of
all genera and species of Acanthodrilinae was undertaken in order to: i) evaluate
if the mesial spermathecal pores justify the status of Lavellodrilus, ii)
determine how common (expressed as percentages of species having the character)
the diagnostic characters of the new species are in the subfamily, iii) clarify
if these characters exhibit a geographical pattern, and iv) contribute towards a
comprehensive analysis of the Acanthodrilinae. In this revision, species were
separated in nine geographical regions: USA, northern Mexico, southern Mexico,
Caribbean Islands (northern hemisphere), and South America, South Africa,
Madagascar, Australia, New Zealand, New Caledonia and Antarctic Islands (southern
hemisphere). As a result of the revision it was found that among the 511
recognized species of Acanthodrilinae only 11 species have a mesial location of
the spermathecal pores, in two cases probably representing monophyletic groups
(Lavellodrilus and a group of South African Parachilota species). It was also
found that the distinguishing characters in L. notosetosus sp. nov., notably the
location of last hearts, genital setae and the first intestinal segment, are
uncommon characters in the acanthodriline earthworm fauna of southern Mexico and
Central America, but more frequent in North America, the Caribbean, and the
southern hemisphere. We conclude that the acanthodrilines from the northern
hemisphere are morphologically more similar to those from Australia, New Zealand,
and New Caledonia than to those of South Africa and South America.
PMID- 27615830
TI - Five new species of Geranomyia Haliday, 1833 (Diptera, Limoniidae) from China.
AB - The following five new species of the genus Geranomyia from China are described
and illustrated: G. baisensis sp. nov., G. degenerata sp. nov., G. longispina sp.
nov., G. maculata sp. nov. and G. nigra sp. nov.. Three known species, G.
apicifasciata (Alexander, 1930), G. radialis (Alexander, 1930) and G.
sparsiguttata (Alexander, 1937), are listed with new distribution data. A key to
the species of the genus Geranomyia from China is presented.
PMID- 27615831
TI - Taxonomy of two endemic Indian skinks, Eutropis bibronii (Gray, 1838)
and E.
nagarjunensis (Sharma, 1969) (Reptilia: Scincidae), including redescriptions of
their types.
AB - Tiliqua bibronii was described by J.E. Gray in December, 1838 based on two
syntypes (MNHN-RA 2940, 7076), but the details for locality was missing. These
syntypes are currently housed at the Museum national d'Histoire naturelle, Paris,
France (MNHN-RA). The same species (based on the same type specimens) was
described by A.M.C. Dumeril & G. Bibron in November, 1839 nearly one year after
Gray's publication. As such, Gray's publication must therefore be given priority.
Another species, Euprepis trilineatus, from Madras, Tamil Nadu, India, was
described by Gray in 1846, and it is morphologically similar to E. bibronii.
Later, Boulenger (1885) synonymised it with E. bibronii. Eutropis bibronii has
subsequently been recorded from other parts of India and Sri Lanka by various
authors. Many years later, a closely related species, Mabuya nagarjuni (sic)
Sharma, 1969, was described from Andhra Pradesh, India, based on two specimens (a
holotype and a paratype) housed at the Zoological Survey of India, Kolkata (ZSI).
Here we make a correction for the species epithet as "nagarjunensis" which should
be a toponym, not a patronym. Among the skink collections at the Natural History
Museum, London (BMNH), ZSI, and MNHN-RA we found E. bibronii specimens collected
from various locations in India, but we were unable to find any specimens from
Sri Lanka. Based on morphological evidence, E. bibronii represents a single,
fairly widespread, species which has to be considered endemic to India. Although,
recent phylogenetic studies reveal a distinct genetic divergence between E.
bibronii and E. nagarjunensis, both species are morphologically very similar to
each other. Here, we examine the morphology of E. nagarjunensis based on the ZSI
specimens. A comprehensive comparison between the syntypes of E. bibronii and
Euprepis trilineatus confirms that the latter nomen is a junior synonym of the
former. The original description of E. bibronii is extremely concise and lacks
most of the important diagnostic characters, so here we provide a comprehensive
redescription of the species based on the examination of its syntypes.
PMID- 27615832
TI - Redescription of Pseudotropheus livingstonii and Pseudotropheus elegans from Lake
Malawi, Africa.
AB - Pseudotropheus livingstonii and P. elegans are two sand-dwelling cichlid species
that belong to the so-called mbuna, a group of predominantly rock-dwelling
haplochromines of Lake Malawi. The identity of these two species has confused
taxonomists for almost a century until a recent rediscovery of representatives of
P. elegans close to its type locality. New diagnoses for both species are
provided.
PMID- 27615833
TI - Redescriptions and new host records of chewing lice of the genus Ricinus
(Phthiraptera: Ricinidae) from the Neotropical Region.
AB - Two species of the chewing louse genus Ricinus are redescribed and illustrated:
Ricinus dalgleishi Nelson, 1972 from Helmitheros vermivorum (Gmelin, 1789), a new
host-louse association, and Ricinus tanagraephilus Eichler, 1956 from Euphonia
laniirostris d'Orbigny & Lafresnaye, 1837. Also, new host-louse associations are
recorded for Ricinus vireoensis Nelson, 1972 from Vireo pallens Salvin, 1863, and
for females of an unidentified species of Ricinus sp. from Corythopis delalandi
(Lesson, 1831), which are described and illustrated.
PMID- 27615834
TI - A new species of the genus Asthenara Forster, 1869 (Hymenoptera, Ichneumonidae)
from Mexico with identification key.
AB - The genus Asthenara Forster, 1869, belonging to the tribe Pionini of the
subfamily Ctenopelmatinae (Hymenoptera, Ichneumonidae), comprises eight described
species (Yu et al. 2012). Two of them are distributed in the Palaearctic Region,
and six in the Neotropical region. One Neotropical species is known from Costa
Rica (Gauld et al. 1997), the remaining five from Mexico (Kasparyan 2006).
Kasparyan (2006) provided a key to the species from the Mexico. To date, no
species of the genus have been described from Nearctic region or south of Costa
Rica. In this article a new species belonging to Asthenara, collected in the
Mexican state of Jalisco is described.
PMID- 27615835
TI - On the type series of Scinax perpusillus (Lutz & Lutz, 1939) (Anura: Hylidae).
AB - The literature regarding the type series of Scinax perpusillus (Lutz & Lutz,
1939) presents two distinct numbers for the holotype. In 1973, thirty-four years
after the description, Bertha Lutz associated numbers to the type series. This
numbering has been followed by subsequent reviewers of Scinax ever since, with
exception of Peixoto (1987) who assigned another number to the holotype. Our
reevaluation of the literature and examination of the type series allowed us to
access that, in both cases, the numbers were incorrectly assigned to the
specimens and determine the proper museum numbers for this series.
PMID- 27615836
TI - Nomina nova in Platyhelminthes pro Macrorhynchus von Graff, 1882 (non [Gmelin,
1801]; non Dunker, 1843), and Leptocleidus Mueller, 1936 (non Andrews, 1922).
AB - Two genus-group names of flat-worms-Leptocleidus Mueller, 1936 and Macrorhynchus
von Graff, 1882-are junior homonyms that are preoccupied by fossil diapsid
reptile genera-Leptocleidus Andrews, 1922, and Macrorhynchus Dunker, 1843-and an
extant teleost fish genus-Macrorhynchus [Gmelin, 1801] ex La Cepede, 1800. These
are replaced by nomina nova (Pharyngodytes nom. nov.; Graffiellus nom. nov.).
Macrorhynchus [Gmelin, 1801] is an objective senior synonym of Macrorhyncus
Dumeril, 1805 ex La Cepede, 1800 (syn. nov.), and a senior homonym of
Macrorhynchus Dunker, 1843, and Macrorhynchus von Graff, 1882.
PMID- 27615837
TI - Revision of the Ambrysus guttatipennis Stal species complex (Heteroptera:
Naucoridae: Cryphocricinae) with the descriptions of six new species from Mexico.
AB - The Ambrysus guttatipennis Stal species complex is revised and includes A.
arizonus La Rivers, A. bispinus La Rivers, A. drakei La Rivers, A. guttatipennis
Stal, A. mexicanus Montandon, and A. mormon Montandon. Six new species that
belong to this complex are described from Mexico: A. ayoyolin n. sp., A. bowlesi
n. sp., A. contrerasi n. sp., A. itsipatsari n. sp., A. noveloi n. sp., and A.
veracruzanus n. sp. The subspecies A. mormon australis La Rivers, A. m.
heidemanni Montandon, and A. m. minor La Rivers are proposed as junior synonyms
of A. m. mormon Montandon. A supplemental redescription of A. guttatipennis Stal
based on the holotype is provided and a lectotype of A. mexicanus Montandon is
designated. Ambrysus arizonus is newly recorded from Mexico and A. bispinus from
Guatemala. Most of the species in this complex occur only in Mexico, although A.
arizonus and A. mormon are distributed in Mexico and the United States, and A.
bispinus is distributed in Mexico and Guatemala. Ambrysus mormon has the widest
distribution of any species in this complex. Features uniting these species are
related to male genitalia and structures associated with male and female
genitalia.
PMID- 27615838
TI - Endemism and long distance dispersal in the waterfleas of Easter Island.
AB - Easter Island is known for a depauperate terrestrial and aquatic biota. The
discovery of new taxa is unusual, even among the island's micro-invertebrates. A
new cladoceran, Ovalona pascua sp. nov. (Crustacea: Cladocera: Anomopoda:
Chydoridae), is described from freshwater environments. The chydorid, the only
known extant cladoceran on the island, is the dominant aquatic invertebrate in
the surface waters. Based on detailed morphological comparison, including a
character similarity matrix applied across the species in the genus (12
characters/17 spp), the new taxon is proposed here as an insular endemic with
affinities in the East (New World). The revision challenges the theory that
invasive zooplankton species were introduced from the subantarctic islands during
the 18th century. Human introduction is not the main mechanism through which
cladocerans could have arrived on Easter Island. Late Pleistocene - Early
Holocene fossils in Canellas-Bolta et al. (2012) from cores in Rano Raraku Lake
are identified here as Daphnia O.F. Muller, 1785 (subgenus Ctenodaphnia Dybowski
& Grochowski, 1895). The establishment of Daphnia before human colonization on
Easter Island provides strong proof of successful long distance dispersal by
ephippia over thousands of kilometers of open sea.
PMID- 27615839
TI - An updated checklist of the Recent non-marine Ostracoda (Crustacea) of Iran, with
a redescription of Eucypris mareotica (Fischer, 1855).
AB - An updated checklist of the extant non-marine Ostracoda of Iran, with 74 species
in all, is presented, based on literature and new collections made in May 2011.
The occurrence of 19 non-marine ostracod species recovered from 10 localities in
May 21-26, 2011 is reported together with ecological data. Eucypris kerkyrensis
Stephanides, 1937, Ilyocypris inermis Kaufmann, 1900, Psychrodromus fontinalis
Wolf, 1920, and P. olivaceus (Brady & Norman, 1889) are new to the fauna of Iran.
Eucypris mareotica (Fischer, 1855) is redescribed and its taxonomic position is
discussed. It is shown that E. mareotica-synonymous with E. inflata-does not
belong to the genus Eucypris sensu stricto, and even not to the subfamily
Eucypridinae; as its characters do not fit any available genus, the species is
therefore provisionally left in the genus Eucypris at present. Eucypris mongolica
(Daday, 1909) is proposed to be considered an infraspecific variety of E.
mareotica. The following new combination is here proposed: Strandesia ambigua
(Ghetti, 1972) nov. comb.
PMID- 27615840
TI - New Black Fungus Gnats (Diptera, Sciaridae) of North America. Part II. Genus
Bradysiopsis Tuomikoski, 1960.
AB - The genus Bradysiopsis Tuomikoski is new for the sciarid fauna of North America.
It includes 6 species. Four of them are new for science. These are Bradysiopsis
postvittigera sp. n., Br. praevittata sp. n., Br. praevittigera sp. n. and Br.
subvittigera sp. n.. Two species, Br. vittata (Meigen, 1830) and Br. vittigera
(Zetterstedt, 1851), are distributed in the Holarctic but new for North America.
In this paper species are described, illustrated by figures and a key for
classification as well as distribution data are given.
PMID- 27615841
TI - Redescription of two European species of Acerentomidae (Protura) belonging to the
Italian fauna.
AB - Acerentulus apuliacus Rusek & Stumpp, 1988 is redescribed based on new specimens
collected in Apulia and Basilicata (S-Italy) and deposited in the collection of
Geneva Natural History Museum. Podolinella ruseki (Nosek, 1967) new combination
is redescribed, based on the holotype from Austria and additional specimens
collected in Liguria, NW Italy. The new material is deposited in the collection
of the Dipartimento di Scienze della Terra, dell'Ambiente e della Vita,
University of Genoa.
PMID- 27615842
TI - Two new planthopper species (Hemiptera, Fulgoroidea, Caliscelidae) collected in
pitfall traps in Zambia.
AB - Two new species of planthoppers in the family Caliscelidae (Hemiptera:
Fulgoroidea) are described from Zambia, i.e., Afronaso spinosa sp. n. and
Calampocus zambiaensis sp. n. All specimens are flightless males and nearly all
were collected from baited pitfall traps (except for one specimen collected from
a yellow pan trap), suggesting that they live near to or on the ground.
PMID- 27615843
TI - Antibothrus morimotoi Sasaji, an Old World cocoon-forming beetle (Coleoptera:
Coccinelloidea: Bothrideridae) newly established in North America.
AB - Antibothrus morimotoi Sasaji, a cocoon-forming beetle (Coccinelloidea:
Bothrideridae) native to the Palearctic region, is newly reported from North
America. In 2013 and 2015, several series of specimens were collected during an
ongoing USDA/APHIS/PPQ exotic bark beetle survey in Franklin County, Ohio, U.S.A.
This is the first confirmed record of the species and genus in the New World. The
capture of these specimens suggests that the beetle is established in the greater
Columbus, Ohio, metropolitan area.
PMID- 27615844
TI - The whale barnacle Cryptolepas rhachianecti (Cirripedia: Coronulidae), a phoront
of the grey whale Eschrichtius robustus (Cetacea: Eschrichtiidae), from a sandy
beach in The Netherlands.
AB - An isolated compartment of a whale barnacle is herein described from Recent beach
deposits in Zoutelande (Walcheren, The Netherlands). This specimen is identified
as belonging to the extant coronulid species Cryptolepas rhachianecti, currently
known as an epizoic symbiont of the grey whale Eschrichtius robustus. This find
represents the first occurrence of C. rhachianecti outside the North Pacific, and
the first one as a (sub)fossil. In view of the fact that E. robustus, which is
currently confined to the North Pacific, is known as a subfossil from the
northeastern Atlantic between late Late Pleistocene (c. 45,000 years ago) and
historical (c. 1700 AD) times, we propose a similar (late Quaternary) age for the
isolated compartment. The find indicates that the extinct late Quaternary
northeastern Atlantic population of E. robustus was infected by Cryptolepas
rhachianecti. Our find is, therefore, compatible with the hypothesis of an
ancient grey whale migration route running between the subtropical/temperate
waters of the northeast Atlantic (or Mediterranean Basin), and the cold waters of
the Baltic Sea (or southern Arctic Ocean), through the southern North Sea.
Finally, we discuss the systematic placement of the fossil barnacle species
Cryptolepas murata and propose the possibility of its removal from the genus
Cryptolepas pending further investigations.
PMID- 27615845
TI - Review of the cave cricket genus Tamdaotettix Gorochov with a new species and
some new descriptions (Orthoptera: Rhaphidophoridae, Aemodogryllinae).
AB - A review of the rhaphidophorid genus Tamdaotettix Gorochov, 1998 is presented.
One new species, one newly-recorded species from China and one species from
Vietnam are identified and described. These are namely Tamdaotettix
(Tamdaotettix) tridenticulatus sp. nov., Tamdaotettix (Laotettix) curvatus
Gorochov, 2015 and Tamdaotettix (Tamdaotettix) semipullus Gorochov, 1998. At the
same time, Megadiestramima extensa Gorochov, 1998 is redescribed. A key to the
species of Tamdaotettix is provided.
PMID- 27615846
TI - A new species of the genus Tetratoma Fabricius (Coleoptera, Tetratomidae) from
China.
AB - A new species of tetratomid beetle, Tetratoma (s. str.) yunnanensis Nikitsky sp.
nov. is described from Southern China (Yunnan). Description, colour habitus
photographs and an illustration of the aedeagus are provided, and the species is
compared with other members of the genus. Biogeographical observations on the
species and subgenera of Tetratoma are given.
PMID- 27615847
TI - An annotated checklist and key to the Bulgarian cockroaches (Dictyoptera:
Blattodea).
AB - An annotated checklist of the Bulgarian species of cockroaches is prepared based
on a full published scientific record and own unpublished data. According to the
current state of knowledge the Bulgarian cockroach fauna includes 17 species and
subspecies. One synonymization is established-Phyllodromica marginata erythronota
Br. v. W., syn. n. = Ph. marginata. Two species (Capraiellus tamaninii and
Supella longipalpa) are recorded for the first time for this country and other
three (Ectobius punctatissimus, Phyllodromica subaptera and Phyllodromica
pallida) are eliminated from the list of the Bulgarian fauna. The list is
complemented with maps and full locality data and a dichotomic identification key
for the studied taxa is presented.
PMID- 27615848
TI - New deep-sea Paratanaoidea (Crustacea: Peracarida: Tanaidacea) from the
northeastern Gulf of Mexico.
AB - One new genus is erected and four new species of paratanaoidean tanaidaceans are
described from deep waters in the northeastern Gulf of Mexico: one in each of the
genera Collettea, Tanaella, and Pseudomacrinella, and one as a new genus in the
family Anarthruridae. Keys to species in the genera Collettea, Tanaella, and the
genera of the Anarthruridae are provided.
PMID- 27615849
TI - A new species of the Scinax catharinae group (Anura: Hylidae) from southeastern
Brazil.
AB - We describe a new species of the Scinax catharinae group from coastal forest in
the State of Sao Paulo, Brazil. We also describe the karyotype and the
advertisement call of the new species, which is composed by a multipulsed note.
The chromosome morphology of the new species shows the nucleolar organizer region
(NOR) on Pair 6, a putative synapomorphy previously inferred for the S.
catharinae clade. We report, for the first time, the presence of mental glands in
a species of the genus Scinax. Additionally, we provide a brief discussion about
the occurrence of glandular tissue on the mental and inguinal regions of the
species of the S. catharinae clade.
PMID- 27615850
TI - New and little known species of Halolaelaps (Acari: Mesostigmata: Halolaelapidae)
from Ukraine.
AB - A new species of the family Halolaelapidae (Acari: Mesostigmata), Halolaelaps
euxinus sp. nov. is described from Black Sea coast. Adult mites were found in
seaweed, while deutonymphs were collected from the amphipod Talorchestia
deshayesii and from seaweed. The adult female of Halolaelaps saproincisus
Hirschmann & Gotz, 1968 is recorded in new localities of Ukraine for the first
time, in soil and bird faeces in chicken coops, and new morphological information
is provided. The adult male (collected from chicken coops) and the deutonymph
(collected from chicken coops and on dung-beetles) of H. saproincisus are
described for the first time.
PMID- 27615851
TI - A new species of Neparholaspis (Acari: Parholaspididae) from Russia, with
additional information on Neparholaspis evansi Krantz, 1960.
AB - Neparholaspis dubatolovi sp. nov. is described and illustrated from adult females
and males collected from litter and moss in montane forest in north-eastern
Sikhote-Alin Ridge in the Far East of Russia. Additional morphological
information and illustrations of Neparholaspis evansi Krantz, 1960 are provided,
based on examination of a paratype. A key to the world species of Neparholaspis
is provided.
PMID- 27615852
TI - First record of Plethus Hagen (Trichoptera, Hydroptilidae) from Japan, with
description of a species.
AB - The tropical and subtropical caddisfly genus Plethus Hagen (Hydroptilidae) is
recorded from Japan for the first time. The species, Plethus ukalegon Malicky and
Chantaramongkol 2007, originally described from Taiwan, is redescribed based on
material from Iriomote-jima and Ishigaki-jima, southern Ryukyu Islands, the
southernmost region of Japan. Female and immature stages are newly described and
compared with Indonesian congeners. The early instar larva was associated with
the adult through mitochondrial DNA sequence comparisons, and is described in the
genus Plethus for the first time. Larvae live in fast-flowing waters such as
hygropetric zones, rapid streams, and waterfalls. Final instar larvae make
flattened cases of silk that they attach tightly on smooth rock surfaces.
PMID- 27615853
TI - A new species of Munidopsis Whiteaves, 1874 (Crustacea: Decapoda: Anomura) from
the Northwest Indian Ocean Ridge.
AB - A new species, Munidopsis militaris n. sp., from the Carlsberg Ridge, Northwest
Indian Ocean Ridge is described herein. The species belongs to a group of species
having a pair of epigastric spines, mesial and lateral eye-spines, abdominal
tergites unarmed, five or six spines on the lateral margin of the carapace, and a
denticulate carina on the distolateral margin of the P1 fixed finger. It can be
distinguished from its relatives by the spinous lateral margin of the palm and
dorsal carinae on the P2-4 propodus. The Munidopsis fauna of the Indian Ocean
Ridge is seldom reported on; this new species is the sixth member of this genus
found inhabiting the Indian Ocean Ridge.
PMID- 27615854
TI - Review of the genus Chrysoscota in Cambodia (Lepidoptera, Erebidae, Arctiinae),
with description of a new species.
AB - The genus Chrysoscota Hampson, 1900 in Cambodia is reviewed, with description of
a new species, Chrysoscota kimsuni Bayarsaikhan & Bae, sp. n. is described as new
to sciences, and C. cotriangulata Holloway, 2001 is reported as new for the
country. Illustrations of adults and male and female genitalia are provided for
both species, with a checklist of the genus Chrysoscota.
PMID- 27615855
TI - On the type species of the genus Aetius O. Pickard-Cambridge, 1896: The first
description of male with notes on cymbial notch and mating plug (Araneae:
Corinnidae: Castianeirinae).
AB - The rare ant mimicking sac spider genus Aetius was erected by O. Pickard
Cambridge in 1896 based on an unspecified number of female specimen(s) collected
from Sri Lanka. The type species of the genus, A. decollatus O. Pickard
Cambridge, 1896, has been redescribed twice based on the holotype (Majumder &
Tikader 1991; Deeleman-Reinhold 2001). Reimoser (1934) recorded the genus for the
first time from India, who collected a male specimen from Mudumalai Tiger Reserve
in Tamil Nadu State of southern India. This specimen was identified as A.
decollatus, but it was never formally described and was later recognised to be a
penultimate male (Dankittipakul & Singtripop 2013). Deeleman-Reinhold (2001)
described the second representative of the genus, A. nocturnus, based on a single
female specimen from Borneo, 105 years after the establishment of the genus.
Dankittipakul & Singtripop (2013) described the male of A. nocturnus, thereby
revealing the male genitalia of the genus, but the type species was still known
only from the female sex.
PMID- 27615856
TI - The Peacock Spiders (Araneae: Salticidae: Maratus) of the Queensland Museum,
including six new species.
AB - Six new species of the peacock spider genus Maratus Karsch, 1878 are described
from Australia: M. eliasi sp. nov., M. julianneae sp. nov., M. licunxini sp.
nov., M. michaelorum sp. nov. and M. ottoi sp. nov. from Queensland, and M.
kiwirrkurra sp. nov. from Western Australia. Five species groups are further
documented within the genus and new records, detailed SEM and automontage images
are provided for six previously described species: M. anomalus Karsch, 1878, M.
chrysomelas (Simon, 1909), M. digitatus Otto & Hill, 2012, M. pavonis (Dunn,
1947), M. speciosus (O.P.-Cambridge, 1874) and M. volans (O.P.-Cambridge, 1874).
PMID- 27615857
TI - New taxonomic, stratigraphic, and geographic information on the genus
Faksephyllia Floris, 1972 (Scleractinia; Caryophylliidae); first records from the
Oligocene of Austria, Germany, and Italy.
AB - The scleractinian genus Faksephyllia Floris, 1972, is revised based on the study
of original and topotypic material as well as original descriptions.
Representatives of this genus have been reported from only a small number of
lower Paleogene localities, including the Danian of Azerbaijan, Denmark
(Greenland), Kazakhstan, and Sweden, as well as the Paleocene of Austria and
Denmark (Fakse). New material belonging to the type species of Faksephyllia (F.
faxoensis) is described from the Lower Oligocene of Austria (Northern Calcareous
Alps, Tyrol). In addition, material from the Oligocene of Germany and the Lower
Oligocene of Italy, formerly grouped with the genera Calamophyllia and
Rhabdophyllia, are here re-assigned and transferred to Faksephyllia. The genus
Faksephyllia remains a monospecific taxon, including only the type species,
Faksephyllia faxoensis (Beck, in Lyell). In addition, Faksephyllia represents the
earliest colonial genus among the caryophylliids.
PMID- 27615858
TI - Taxonomic revision of the Neotropical genus Caenopangonia Krober, 1930 (Diptera:
Tabanidae).
AB - The Neotropical species of Caenopangonia Krober are revised herein based on
examination of external and internal morphology of type material and specimens
from Argentina and Chile. Three currently valid species are recognized:
Caenopangonia aspera (Philip, 1958), Caenopangonia brevirostris (Philippi, 1865),
and Caenopangonia hirtipalpis (Bigot, 1892). Two new species are described,
Caenopangonia cerdai n. sp. Krolow, Henriques & Gonzalez (Chile, Chacabuco) and
Caenopangonia coscaroni n. sp. Krolow, Henriques & Gonzalez (Chile, Malleco). We
provide diagnosis and/or descriptions, distribution records, illustrations and
discussion for all species, as well a key for identification.
PMID- 27615859
TI - Odontotrypes (Odontotrupes) tawangensis new species (Coleoptera: Geotrupidae)
from Arunachal Pradesh, India.
AB - A new species of the genus Odontotrypes Fairmaire, 1887 (Coleoptera: Geotrupidae)
belonging to the subgenus Odontotrupes Boucomont, 1905 is described from the
Tawang district, State of Arunachal Pradesh (northeast India): Odontotrypes
(Odontotrupes) tawangensis new species. Relevant diagnostic characters (pronotum,
head, elytra, profemur, scutellar shield, and external male genitalia) are
illustrated and compared with closely related species of this subgenus, in
particular Odontotrypes (Odontotrupes) orichalceus (Fairmaire, 1895). The
distribution of the new species is mapped.
PMID- 27615860
TI - Record of a new species of the genus Viridopromontorius Luna de Carvalho
(Strepsiptera: Corioxenidae) from India with a revised key to Corioxenidae.
AB - A new species of the genus Viridopromontorius Luna de Carvalho is described from
West Bengal, India. The new species V. aequus differs from the other member of
Viridopromontorius by having approximately equal size of antennomeres IV and V,
maxillary palp nearly twice the length of base, vein R4 curved towards
R2, very small distal process on tarsomeres II-III, tarsomere IV
almost trapezoidal and acumen to some extent upwardly bent (in lateral view). A
revised key of the family Corioxenidae is also provided.
PMID- 27615861
TI - A new species of Janusius Bretfeld, 2010 (Collembola, Sminthuridae) from the
Korean Peninsula, with a key to the species of the genus.
AB - Janusius geumgangensis sp. nov. is described and illustrated based on specimens
from North Korea. The new species is characterised by having 3 spatulate chaetae
on all tibiotarsus, 4 chaetae on retinaculum, smooth anal appendage, anterior
chaetotaxy of dens 3,3,3,2,2,1,1, colouration with one pair brownish lateral spot
and presence of mucronal chaeta. The genus Janusius Bretfeld, 2010 is first
mentioned from the Korean Peninsula, although another species described from
there as Sminthurus annulatus Kang & Lee, 2005 is recognised here as belonging to
this genus (Janusius annulatus (Kang & Lee, 2005) comb. nov.), too. A key
including all known species of the genus is presented as well.
PMID- 27615862
TI - Review of the plant bug genus Fingulus Distant in Indochina (Hemiptera:
Heteroptera: Miridae: Deraeocorini), with descriptions of two new species.
AB - The deraeocorine plant bug genus Fingulus Distant from Indochina is reviewed,
diagnosed and discussed. Seven species are currently recognized, including two
new species described herein: F. angkorensis and F. rubricatus from Cambodia and
Thailand. Behavior and habitat of F. angkorensis are documented, which was
observed to be associated with two anthocorids and a thrips in leaf margin curl
galls produced by the thrips on a banyan tree Ficus microcarpa. A checklist
including two species of the assumed sister genus Angerianus Distant is provided,
with available distributional records; images of two Angerianus species are also
shown for the first time.
PMID- 27615863
TI - A new record of the genus Discoelius Latreille, 1809 (Hymenoptera: Vespidae:
Eumeninae) from Northern Vietnam with description of two new species.
AB - The genus Discoelius Latreille, 1809, is newly recorded from Vietnam. Discoelius
aurantiacus Nguyen, sp. nov. and D. nigerrimus Nguyen, sp. nov. are described and
figured from Northern Vietnam (Lao Cai).
PMID- 27615864
TI - Two new species of South American Glaresidae (Coleoptera: Scarabaeoidea).
AB - Two new species of South American Glaresidae (Coleoptera: Scarabaeoidea) are
described: Glaresis smithi Paulsen, new species from Argentina, and Glaresis
mondacai Paulsen, new species from Chile and Peru. The species are compared to
their closest congener, Glaresis fritzi Martinez et al., and a key is provided
for the known South American species of the genus Glaresis Erichson.
PMID- 27615865
TI - Species boundaries and taxonomy of the African river frogs (Amphibia:
Pyxicephalidae: Amietia).
AB - A molecular phylogeny of the Afrotropical anuran genus Amietia based on 323 16S
sequences indicates that there are 19 species, including four not yet described.
No genetic material was available for the nominal A. inyangae. We consider them
to represent full species, and define them based on 16S genetic distances, as
well as differences in morphology, tadpoles and advertisement call where known.
An analysis based on two mitochondrial and two nuclear genes (12S, 16S, 28S and
tyrosinase exon 1), from 122 samples, confirmed the phylogenetic relationships
suggested by the 16S tree. We recognise and (re-) describe the following species:
Amietia angolensis (Bocage, 1866), A. chapini (Noble, 1924), A. delalandii
(Dumeril & Bibron, 1841), A. desaegeri (Laurent, 1972), A. fuscigula (Dumeril &
Bibron, 1841), A. hymenopus (Boulenger, 1920), A. inyangae (Poynton, 1966), A.
johnstoni (Gunther, 1893), A. moyerorum sp. nov., A. nutti (Boulenger, 1896), A.
poyntoni Channing & Baptista, 2013, A. ruwenzorica (Laurent, 1972), A.
tenuoplicata (Pickersgill, 2007), A. vandijki (Visser & Channing, 1997), A.
vertebralis (Hewitt, 1927), and A. wittei (Angel, 1924). Three further candidate
species of Larson et al. (2016) await formal naming. We provisionally regard A.
amieti (Laurent, 1976) as a junior synonym of A. chapini (Noble, 1924). Amietia
lubrica (Pickersgill, 2007) is shown to be a junior synonym of A. nutti, while A.
quecketti (Boulenger, 1895) is shown to be a junior synonym of A. delalandii
(Dumeril & Bibron, 1841), and A. viridireticulata (Pickersgill, 2007) is placed
as a junior synonym of A. tenuoplicata (Pickersgill, 2007). On the basis of
similarity of 16S sequences, we assign A. sp. 1, A. sp. 3 and A. sp. 6 of Larson
et al (2016) to the nomina A. chapini (Noble, 1924), A. desaegeri (Laurent,
1972), and A. nutti (Boulenger, 1896) respectively.
PMID- 27615866
TI - Review of amphipods of the Melita group (Amphipoda: Melitidae) from the coastal
waters of Sakhalin Island (Far East of Russia). III. Genera Abludomelita Karaman,
1981 and Melita Leach, 1814.
AB - The taxonomic analysis of Melita group is performed. The revision of the genus
Melita Leach, 1814 was held on the basis of analysis of morphological characters.
Cladistic analysis of morphological relationships within genera Abludomelita and
Melita is performed. Status of the genus Paraniphargus Tattersall, 1925 restored.
New genera Barnardomelita gen. nov. and Ledoyeromelita gen. nov. are described
and removed from the composition of the genus Melita. A review of Melita group
(fam. Melitidae) from the shelf of Sakhalin Island based on all literature and
own data is provided. Based on new material, two new species of the genus
Abludomelita Karaman, 1981 are described: A. klitinii sp. nov. and A. okhotensis
sp. nov. from the shelf of Sakhalin Island. Megamoera aequidentatum Labay, 2013
is transferred to the genus Abludomelita as A. rotundactyla (Ren, 2012) on the
basis of additional morphological description of male. The new subspecies Melita
shimizui sakhalinensis ssp. nov. is described from estuaries of Sakhalin Island.
The keys to the world species of genera Abludomelita and Melita are provided.
PMID- 27615867
TI - Diversity of Scydmaeninae (Coleoptera: Staphylinidae) in Upper Eocene Rovno
amber.
AB - Among nearly 1270 inclusions of Coleoptera found in Upper Eocene Rovno amber, 69
were identified as ant-like stone beetles (Scydmaeninae); 34 were possible to
unambiguously determine to the tribal level and were studied in detail.
Rovnoleptochromus ableptonoides gen. & sp. n. (Mastigitae: Clidicini), Vertheia
quadrisetosa gen. & sp. n. (Cephenniitae: Eutheiini), Cephennomicrus giganteus
sp. n. (Cephenniitae: Cephenniini), Glaesoconnus unicus gen. & sp. n.
(Scydmaenitae: Glandulariini), Rovnoscydmus frontalis gen. & sp. n.
(Scydmaenitae: Glandulariini; type species of Rovnoscydmus), Rovnoscydmus
microscopicus sp. n., Euconnus (incertae sedis, near Cladoconnus) palaeogenus sp.
n. (Scydmaenitae: Glandulariini), and Stenichnus (s. str.) proavus sp. n.
(Scydmaenitae: Glandulariini) are described. Additionally, specimens representing
one undescribed species of Vertheia, one of Cephennodes, five of Cephennomicrus,
one of Euconnus, one of Microscydmus are recorded, and nine specimens
representing an unknown number of species of Rovnoscydmus (and two putative
Rovnoscydmus), one Euconnus (and one putative Euconnus), two putative
Microscydmus and one putative Scydmoraphes were found in the studied material.
The composition of Scydmaeninae fauna in Rovno amber is discussed in the context
of ecological preferences and distribution of extant taxa. It is concluded that
subtropical and tropical taxa were present in the region where Rovno amber has
formed, most notably the second genus and species of the extant tribe Clidicini
known from the Eocene of Europe, and six species of the extant genus
Cephennomicrus, for the first time found in the fossil record. An annotated
catalog of nominal species of Scydmaeninae known in the fossil record is given.
PMID- 27615868
TI - An annotated taxonomic checklist of the Neotropical Gracillariidae (Lepidoptera)
with links to the information on host plants and parasitoids.
AB - This comprehensive checklist is a synthesis of the verified taxonomic information
on all known Neotropical Gracillariidae species presented in a concise and
uniformed way. The taxonomic information on these moth species in the Neotropical
region is assembled and presented along with the referenced information on
species distribution, host plants and parasitoids. The Genbank and BOLD accession
numbers are given for the species that have been genetically investigated. By
consulting robust literature sources, the Gracillariidae collections at natural
history museums and in private holdings, we emphasize the significance of inter
links between the information on host plants, gracillariid moths and their
parasitoids in the Neotropical Region.
PMID- 27615869
TI - A new species of Leioseius (Acari: Ascidae) from Brazil, redescription of
Leioseius basis and a key for separation of the world species of the genus.
AB - Leioseius Berlese is known in South America only from one especies described from
Chile. Leioseius cananeiensis n. sp. is described based on the morphology of
adult females found in association with barnacles (Crustacea, Cirripedia) on
roots of Laguncularia racemosa (L.) (Combretaceae) collected in Cananeia, Sao
Paulo State, Brazil. Leioseius basis Karg is redescribed based on the holotype
female, one paratype female and two sparatype males. A key for the separation of
females of the 19 recognisable world Leioseius species is provided.
PMID- 27615870
TI - New species of Hercostomus Loew, 1857 (Dolichopodidae, Diptera) from Japan.
AB - Six new species of the genus Hercostomus Loew, 1857, are described from Japan:
Hercostomus acutiformis Negrobov, Kumazawa & Tago sp. nov., H. falcilis Negrobov,
Kumazawa & Tago sp. nov., H. flavipalpus Negrobov, Kumazawa, Tago & Sato sp.
nov., H. nigricollaris Negrobov, Kumazawa & Tago sp. nov., H. spathulatus
Negrobov, Kumazawa, Tago & Sato sp. nov., H. spinitibialis Negrobov, Kumazawa &
Tago sp. nov. Hercostomus flaveolus Negrobov & Chalaya, 1987 is newly recorded
from Japan, and Hercostomus arcticus Yang, 1996 is newly synonymized with
Hercostomus flaveolus (syn. nov.). The holotype of Hercostomus flaviventris
Smirnov & Negrobov, 1979 is redescribed. Hercostomus ussurianus Stackelberg is
transferred to the genus Gymnopternus Loew, 1857 (stat. nov.). A key to the
eleven recognized species of Japanese Hercostomus is provided.
PMID- 27615871
TI - Revision of the Rhinophoridae (Diptera: Calyptratae) of Japan.
AB - The Japanese species of the family Rhinophoridae are revised. Melanophora roralis
(Linnaeus) is newly recorded from Japan and is hypothesized as having been
introduced to the country; one species, Acompomintho itoshimensis sp. nov., is
described as new. Images of the habitus, wing and male terminalia are provided
for all four Japanese species, together with an identification key and a map
showing their distribution.
PMID- 27615872
TI - Cerapanorpa, a new genus of Panorpidae (Insecta: Mecoptera) with descriptions of
three new species.
AB - A new genus of Panorpidae (Mecoptera), Cerapanorpa gen. nov., is erected with
Panorpa obtusa Cheng, 1949 as its type species. The new genus can be readily
recognized by having a single digitate anal horn on the posterior edge of tergum
VI in males, and a broad main plate bearing two pairs of basal plates at the
genital plate and a well-developed elongate axis in females. Nineteen described
species are transferred from Panorpa Linnaeus, 1758 to the new genus. In
addition, three new species, Cerapanorpa liupanshana sp. nov., Cerapanorpa
protrudens sp. nov. and Cerapanorpa sinuata sp. nov. are described and
illustrated. Panorpa alticola Zhou, 2000 syn. nov. is regarded as a junior
synonym of P. obtusa Cheng, 1949. A key to genera of Panorpidae is updated to
include the new genus. A key to species of Cerapanorpa is also presented.
PMID- 27615873
TI - New Genus and species of Heteroxyidae from Brazil (Axinellida: Demospongiae:
Porifera), with a revised identification key for the family.
AB - Alveospongia sinuosclera gen. nov. sp. nov. is described from shallow-waters off
Canavieiras (Bahia, Brazil). The species bears an unusual morphology, combining
saccular or alveolar, evenly perforated habit, and sinuous spiny microrhabdose
microscleres. This sponge is tentatively classified within the Heteroxyidae Dendy
(1905), on the basis of its confused choanosomal architecture of styles, and
possession of spiny microrhabdose microscleres. Assays to generate DNA sequences
from this material were unsuccessful. We emended the diagnosis of the family to
include species bearing saccular/alveolar shape, microrhabdose
acanthomicrostrongyles and styles/strongyles with modifications at the ends. The
proposed new genus is compared to the remaining heteroxyid genera, as well as
Crella (Crellidae), Batzella (Chondropsidae), Goreauiella (Astroscleridae) and
Sceptrintus (Podospongiidae). A revised key for identification of Heteroxyidae
genera is provided.
PMID- 27615874
TI - Spongillaflies (Neuroptera, Sisyridae) in Baltic amber.
AB - Two spongillaflies species are described and illustrated from Eocene Baltic
amber: Paleosisyra minor n. sp. and Paleosisyra electrobaltica Wichard et al.,
2009; the latter species was described based on a female and is now re-described
in consideration of the male genitalia of two new male specimens. Extant
Sisyridae comprise few species, and their fossil record is very scarce.
PMID- 27615875
TI - The crane fly genus Libnotes Westwood, 1876 (Diptera: Limoniidae) for Korea
including two new species and an identification key.
AB - Two new species of crane flies, Libnotes (Libnotes) charlesyoungi n. sp. and L.
(L.) jirisana n. sp. are described. Libnotes (Afrolimonia) plutonis (Alexander,
1924) is described for the first time on the Korean Peninsula. A key for all
Korean Libnotes spp. is presented.
PMID- 27615876
TI - Two new species of Willowsia (Collembola: Entomobryidae) from Guizhou Province,
China.
AB - The genus Willowsia Shoebotham, 1917 belongs to the family Entomobryidae. Within
the family it is characterised by having 4-segmented antennae, 8+8 eyes, spines
and scales absent from dens, claw with unpaired inner teeth, bidentate mucro and
scales on body. Twenty-six species have been described in the genus worldwide
including eight species from China. Two new species, Willowsia pseudoshi sp. nov.
and W. variabilis sp. nov., from China are described here. The former species has
pale yellow antennae except for distal part of Antenna IV which has some blue
pigment and 4 macrochaetae are present on Abdomen I. The latter species has the
whole antenna pigmented blue and 7-8 macrochaetae present on Abdomen I. A key to
Chinese species of Willowsia is given.
PMID- 27615877
TI - Pseudowuiessa, a new genus of brachypterous Mezirinae (Hemiptera: Heteroptera:
Aradidae) from China.
AB - A new brachypterous flat bug (Hemiptera: Heteroptera: Aradidae) genus and
species, Pseudowuiessa producta Bai, Heiss & Cai, gen. nov. & sp. nov., is
described from Yunnan, China. A key to related genera is given and the diagnostic
characters of the new taxon are illustrated.
PMID- 27615878
TI - Description of the second- and third-instar larva of South African Stenomastigus
longicornis (Boheman) (Coleoptera: Staphylinidae, Scydmaeninae).
AB - The second- and third-instar larvae of the South African species of Mastigini,
Stenomastigus longicornis, are described. The serial homology of chaetotaxic
structures and differences between larval instars are discussed. The larva of
Stenomastigus is very similar to that of Palaeostigus, but differences in
proportions of body parts, number of setae on the head, thorax and abdomen and
possibly also the shape of the antennal sensory appendage can be used to
distinguish them. A frontal impression surrounded by modified setae with greatly
enlarged surface, presumably functioning as a glandular evaporation apparatus,
and the antennomere II subdivided into three sections, are suggested as
synapomorphies of Mastigini; within Mastigitae this tribe is also unique in
lacking the urogomphs, which are present in larvae of Leptomastacini and
Clidicini. Geniculate and slender antennae with a strongly oblique distal margin
of antennomere II are a putative larval synapomorphy of Mastigitae.
PMID- 27615879
TI - Contribution to the knowledge of the genus Singilis Rambur, 1837 of Africa
(Coleoptera: Carabidae: Lebiini). Part IV.
AB - Nine new species of the genus Singilis from Africa are described: Singilis
(s.str.) shavrini sp. n. (Kenya, Tanzania), S. (s.str.) africaorientalis sp. n.
(Ethiopia, Somalia, Tanzania, Kenya, RSA, Zambia, Zimbabwe), S. (s.str.) burtoni
sp. n. (Zambia, Zimbabwe), S. (s.str.) paganeli sp. n. (RSA), S. (s.str.)
somalicus sp. n. (Somalia), S. (s.str.) haekeli sp. n. (Zambia), S. (s.str.)
crypticus sp. n. (Cameroon), S. (s.str.) pallens sp. n. (Namibia) and S. (s.str.)
parvulus sp. n. (Zimbabwe). One new subspecies from Kenya, S. (s.str.)
africaorientalis kenyacus ssp. n., is described too. Differential diagnosis of
the related species Singilis (s.str.) allardi (Basilewsky, 1963), S. (s.str.)
ambulans (Peringuey, 1896), S. (s.str.) cribricollis (Peringuey, 1904), S.
(s.str.) pusillus (Peringuey, 1898) and S. (s.str.) zonata Chaudoir, 1878 is also
proposed. Illustrations of habitus and aedeagus for every species is provided,
and new country records are given.
PMID- 27615880
TI - Recharacterization of Rhinophis dorsimaculatus Deraniyagala, 1941 (Serpentes:
Uropeltidae), including description of new material.
AB - The Sri Lankan uropeltid (shieldtail) snake Rhinophis dorsimaculatus
Deraniyagala, 1941 was described originally from two specimens that were
subsequently lost. The small amount of previously published data and lack of
published colour photographs made this one of South Asia's most poorly known
snake species, and this resulted in at least one instance of taxonomic
misidentification. An additional 10 specimens from a historical collection from
the vicinity of the type locality recently came to light. This material is
reviewed and documented and the species recharacterized. An additional locality
for the species is reported. The newly reported material helps to corroborate the
taxonomic validity and distinctiveness of Rhinophis dorsimaculatus. The species
is readily distinguished from congeners by having 227 or more ventral scales; a
large, dorsally carinate rostral shield; posterior margins of paired anals that
are largely separated by the posteriormost ventral scale; and a distinctive
colour pattern with bilaterally asymmetrical dark blotches within a broad, pale
middorsal stripe and regularly punctate flanks.
PMID- 27615881
TI - Thylacosceles Meyrick new to China, with descriptions of four new species
(Lepidoptera: Stathmopodidae).
AB - The genus Thylacosceles Meyrick, 1889 is recorded from China for the first time.
Thylacosceles nephroides sp. nov., T. clavata sp. nov., T. cuneiformis sp. nov.
and T. ellipsoidala sp. nov. are described as new. Photographs of adults and
genital illustrations are provided, along with a key to the genus in China.
PMID- 27615882
TI - A taxonomic revision of the neotropical termite genus Diversitermes (Isoptera:
Termitidae: Nasutitermitinae).
AB - The taxonomy of the neotropical termite genus Diversitermes Holmgren 1912 is
revised. Three species are recognized as valid: D. castaniceps (Holmgren 1910),
D. diversimiles (Silvestri 1901) and D. tiapuan, sp. n. Identification keys based
on soldiers and workers are presented. Diversitermes aporeticus Mathews 1977 is
transferred to the genus Velocitermes Holmgren 1912. Diversitermes needhami
Roonwal, Chhotani & Verma 1981 is a junior synonym of Velocitermes heteropterus
(Silvestri 1901), and D. eidmanni Roonwal, Chhotani & Verma 1981 is a junior
synonym of D. castaniceps (Holmgren 1910). Eutermes strelnicovi John 1920
(=Nasutitermes strelnicovi) is a junior synonym of D. diversimiles. All castes of
the three valid species are described and illustrated. Distribution maps are
presented for all species.
PMID- 27615883
TI - Nematomorpha from the Philippines, with description of two new species.
AB - With the exception of one species, no horsehair worms (Nematomorpha) were known
to date from the Philippines. We report here several records, almost all from
Panay Island. Two species, Gordius jorriti and Acutogordius finni, are described
as new species. Two species of Chordodes, C. caledoniensis and C. cf. moutoni,
were found. In addition, further specimens from the genera Gordius, Acutogordius
and Chordodes could not be determined to species level.
PMID- 27615884
TI - Ompok argestes, a new species of silurid catfish endemic to Sri Lanka (Teleostei:
Siluridae).
AB - Ompok argestes, a new species of silurid catfish, is described from the
southwestern lowlands of Sri Lanka. The new species is distinguished from all
other species of Ompok in the Indian subcontinent by a combination of the
following characters: body color pattern mottled; predorsal profile uniformly
convex; maxillary barbels reach or extend slightly beyond base of dorsal fin; eye
diameter 14.2-17.1% head length (HL); body depth at anus 19.8-22.3% standard
length (SL); head width 14.3-16.8% SL; caudal peduncle depth 5.6-6.5% SL.
Callichrous ceylonensis Gunther is shown to be a valid species that is apparently
restricted to Sri Lanka, distinguished by a combination of the following
characters: distinct concavity in predorsal profile; origin of pelvic fin beneath
or slightly posterior to the origin of the dorsal fin; maxillary barbels 108-166
% HL; mandibular barbels 16.1-33.7 % HL; and 58-66 anal-fin rays.
PMID- 27615885
TI - New records of Indian Nematomorpha, with the description of a new species from
the genus Chordodes.
AB - Chordodes tjorvenae, a new species of horsehair worms is described from Mizoram,
Northeast India. The species is distinct from all other known species by a unique
combination of cuticular charatcers. In addition, the occurrence of the genus
Acutogordius, particularly A. finni, is reported for the first time from India.
PMID- 27615886
TI - A new species of Crinibracon Quicke (Hymenoptera: Braconidae) parasitic on pupae
of Hasora chromus (Cramer) (Lepidoptera: Hesperiidae) from India.
AB - A new species, Crinibracon chromusae Gupta & van Achterberg sp. n., parasitic on
pupae of Hasora chromus (Cramer) (Hesperiidae) on Millettia (= Pongamia) pinnata
(L.) Panigrahi (Fabaceae), is described from India and compared with C. sinicus
(Yang, Chen & Liu, 2008) from China, the only other species known with a similar
general appearance. For the first time biological information for the genus
Crinibracon Quicke, 1988, is given. Three species of hyperparasitoids, Philolema
braconidis (Ferriere) (Hymenoptera: Eurytomidae), Nesolynx javanica Ferriere
(Hymenoptera: Eulophidae), and an Eupelmus sp. (Hymenoptera: Eupelmidae) emerged
along with C. chromusae sp. n. from pupae of H. chromus. The generic placement of
this new species along with interesting parasitoid biology is discussed.
PMID- 27615887
TI - Erythrodiplax ana sp. nov. (Odonata: Libellulidae) from Brazilian palm swamps.
AB - Erythrodiplax ana sp. nov. (male holotype, six male and three female paratypes),
collected in Vereda wetlands (a unique Neotropical savanna environment) in
Uberlandia (Minas Gerais) and Chapada dos Guimaraes (Mato Grosso), Brazil, is
described and illustrated. The new species fits in Borror's Basalis Group, and
can be distinguished from other species by the combination of the following
traits: blue pruinosity dorsally on thorax and third to eighth abdominal
segments; sides of the thorax olive-green; face ivory or olive-green; wings
hyaline with a small apical brown spot on all four wings, well defined in
females; male genitalia with sclerotized erectile posterior lobe and inflatable
sac-like median process. Last instar larvae were reared in the laboratory,
resulting in the description of the larva. We also followed this population for
13 months and present resulting biological notes and comments on ontogenetic
color change in males, as well as longevity.
PMID- 27615888
TI - Two new species of South American freshwater crayfish genus Parastacus Huxley,
1879 (Crustacea: Decapoda: Parastacidae).
AB - Two new species of Parastacus Huxley, 1879 are described from material collected
in the state of Rio Grande do Sul, southern Brazil: Parastacus fluviatilis sp.
nov. from highland streams and Parastacus caeruleodactylus sp. nov. from
wetlands. Parastacus fluviatilis sp. nov. is distinguished mainly by large
chelipeds with dense setae cover on the cutting edge of fingers, telson
subtriangular with two lateral blunt spines and strongly concave ventral surface
of lateral process of thoracic sternites 6 and 7. Parastacus caeruleodactylus sp.
nov. is distinguished mainly by blue cheliped fingers and a large gap between
them, reduced abdomen, dorsal and ventral margins of dactylus, propodus and
carpus of second pair of pereiopods with tufts of long setae and mid-dorsal
carina of exopod of uropods unarmed. According to IUCN Red List criteria both
species are considered endangered. Habitat characterization and a method for
defining the shape of second abdominal pleura are also provided.
PMID- 27615890
TI - An integrative approach to reappraising species validity in Pseudexostoma
(Teleostei: Sisoridae).
AB - The catfish genus Pseudexostoma (Sisoridae) currently contains three species: P.
yunnanensis from the upper Irrawaddy River (Dayingjiang), and P. brachysoma and
P. longipterus from the upper Salween River (Nujiang). We adopted an integrative
approach combining both morphology-based (traditional measurements, truss-based
and geometric morphometrics, fin skeleton examination and X-ray photography) and
molecular approaches (genetic distances, haplotype network, phylogenetic
relationships) to reappraise species validity in Pseudexostoma. Our results
showed that P. longipterus cannot be distinguished from P. brachysoma from either
morphological or molecular analyses, and that the former name should thus be
considered a junior synonym of the latter. The two remaining geographically
isolated species, P. yunnanensis and P. brachysoma, showed a distinct genetic
distance equated to the typical 2% sequence divergence threshold delineating
different species of fishes, and with a divergence time dated to approximately
1.22-2.14 million years ago. Although P. yunnanensis and P. brachysoma share some
morphological characters that appear gradually diverging (body depth at anus and
interorbital distance), some degree of overlap still exists, we suggest the two
species are distinct based on the total evidence.
PMID- 27615889
TI - The Neotropical tanyderid Araucoderus gloriosus (Alexander) (Diptera,
Tanyderidae), with description of the egg, larva and pupa, redescription of
adults, and notes on natural history.
AB - Larvae, pupae and adults of Araucoderus gloriosus (Alexander) were collected
during fieldwork in Chilean Patagonia, December 2013 and January 2014. Eggs were
obtained from females that oviposited in captivity. Association of all life
stages is based on co-occurrence and rearing of individual larvae to adults. A
diagnosis for the genus and species is provided. Descriptions of the egg, larva
and pupa and redescriptions of the male and female are completed. Eggs of A.
gloriosus are the first described for Tanyderidae. Natural history
characteristics for this species, including microhabitat, copulatory behavior and
oviposition, are discussed.
PMID- 27615891
TI - Review of the genus Siemssenius Weise, 1922 (Coleoptera: Chrysomelidae:
Galerucinae) from Taiwan, with descriptions of five new species.
AB - Taiwanese species of Siemssenius are separated into two species groups, the S.
metallipennis group and S. rufipennis group, based on color patterns and other
morphological characters. Members of the S. rufipennis group cannot be
distinguished using external morphology but may be diagnosed by distributions and
genitalia morphologies. Seven species are recognized in Taiwan, including two
previously described species, S. rufipennis (Chujo, 1962) and S. metallipennis
(Chujo, 1962), and five new species, S. cheni Lee, sp. nov., S. jungchani Lee,
sp. nov., S. liui Lee, sp. nov., S. tsoui Lee, sp. nov., and S. yuae Lee, sp.
nov. Speciation models explaining the high diversity of Siemssenius species in
Taiwan, are discussed.
PMID- 27615892
TI - On the Lathrobium fauna of the Luoxiao Mountains, Central China.
AB - Thirteen species of Lathrobium Gravenhorst, 1802 are recorded from the Luoxiao
Mountains, Central China, all of them micropterous and locally endemic. Eight
species are described and illustrated: L. bamianense Peng & Li sp. n., L. fumingi
Peng & Li sp. n., L. jinyuae Peng & Li sp. n., L. jiulingense Peng & Li sp. n.,
L. shuguangi Peng & Li sp. n., L. taiye Peng & Li sp. n., L. yangshimuense Peng &
Li sp. n., and L. yipingae Peng & Li sp. n. Five probably undescribed species
remain unnamed. Including the new taxa, 219 Lathrobium species are currently
known from mainland China.
PMID- 27615893
TI - Three new genera and three new species of Nearctic Lasiopteridi (Diptera:
Cecidomyiidae: Cecidomyiinae) from Asteraceae and Caprifoliaceae, and the tribe
Rhopalomyiini subsumed under Oligotrophini.
AB - Three new Nearctic genera of gall midges (Diptera: Cecidomyiidae), each with a
new species, are described: Helianthecis Gagne for Helianthecis capitum Gagne,
new species, that lives in flower heads of Helianthus spp. (Asteraceae) from
North Dakota to Texas; Lonicerae Gagne for Lonicerae russoi Gagne, new species,
and Lonicerae lonicera (Felt), new combination, that form bud galls on Lonicera
spp. (Caprifoliaceae) in California; and Chiosperma Gagne for Chiosperma turgidum
Gagne, new species, that forms a bud gall on Symphoricarpos albus (L.) S.F. Blake
(Caprifoliaceae) in Washington. The three new genera belong to the supertribe
Lasiopteridi and are placed in the tribe Oligotrophini. The tribes Oligotrophini
and Rhopalomyiini are combined.
PMID- 27615894
TI - Review of the Eulimnadia (Branchiopoda: Spinicaudata: Limnadiidae) from Argentina
with the description of a new species.
AB - A new spinicaudatan species, Eulimnadia pampa sp. nov., is described from
Argentina mostly based on the differential egg morphology. This species was
collected from rainwater pools from Buenos Aires City and the provinces of Buenos
Aires and Entre Rios, and compared to other Neotropical species. Previous
Argentine record of E. brasiliensis is shown to belong to our new species, which
represents the southernmost Neotropical Eulimnadia. We also present new records
of the Paraguayan Eulimnadia ovisimilis Martin and Belk, 1989 from northeastern
Argentina. Eulimnadia santiaguensis is treated as a species inquirenda, thus we
recognize only three Eulimnadia species in Argentina: E. pampa sp. nov., E.
ovilunata and E. ovisimilis, and we provide a brief indentification key. We
present the first description and SEM images of the putative Eulimnadia
spermatophore, which we found in the new species.
PMID- 27615895
TI - A new species of the genus Paracypria (Crustacea: Ostracoda: Cypridoidea) from
the Fiji Islands.
AB - A new marine species of the genus Paracypria (Paracypria fijiensis n. sp.) is
reported from the Fiji Islands, a small island archipelago in the South Pacific
Ocean. This is the first report of a Paracypria species from the Fiji Islands.
Descriptions of soft parts and valves of Paracypria fijiensis n. sp. are
presented herein, and morphological comparisons are made with existing Paracypria
species from Australia, Japan and New Caledonia. Although eight coastal sites
were sampled across the Fiji Islands, the new Paracypria species was found at
only three sites. Large numbers of P. fijiensis n. sp. were recorded from
intertidal flats, indicating it to be highly tolerant of the dynamic intertidal
zone conditions.
PMID- 27615896
TI - Two new species of the genus Podalonia Fernald from China and a key to the
Chinese species of the genus (Hymenoptera: Sphecidae).
AB - Two new species are described: Podalonia arcuaticlypeata Wang & Ma, sp. nov. from
Xinjiang, China and Podalonia bicellularis Wang & Ma, sp. nov. from Qinghai,
China. A key to the species of Podalonia from China is provided.
PMID- 27615897
TI - Redescription of Cheilinus quinquecinctus Ruppell, 1835 (Pisces: Perciformes,
Labridae), a valid endemic Red Sea wrasse.
AB - The labrid fish Cheilinus quinquecinctus Ruppell, originally described from the
Red Sea, has long been regarded as a junior synonym of C. fasciatus (Bloch).
Herein, both nominal species are redescribed, based on examination of the types
and additional material from the Red Sea (for C. quinquecinctus) and the Indo
West Pacific (for C. fasciatus). Ruppell's description of Cheilinus
quinquecinctus was originally based on three syntypes, and the most
representative adult specimen is designated as the lectotype. We show that
Cheilinus quinquecinctus is restricted to the Red Sea and the Gulf of Aden, and
it differs from the similar C. fasciatus in having modally fewer gill rakers on
the first gill arch, a total of 13-16 (mean 13.9, usually 13 or 14 ) (vs. 13-16,
mean 14.7, usually 14 or 15), in developing a ragged posterior margin of the
caudal fin with age (versus only upper and lower caudal-fin lobes developing with
age), and in its color pattern. The phylogenetic analysis of the COI barcoding
region accords with the species status of C. quinquecinctus with the placement of
the two sister species in two divergent and reciprocally monophyletic
evolutionary lineages. A full description of C. quinquecinctus and diagnosis of
C. fasciatus is provided here for comparison. In addition, the data include a
table of the results of the meristic and morphological examination of type and
additional specimens of both species from throughout their distribution ranges as
well as a table of gill-raker counts of all examined specimens. Underwater color
photographs are provided for comparison of juveniles, females and males of both
species.
PMID- 27615898
TI - Four new species of Lorryia (Acari: Tydeidae) associated with Hevea brasiliensis
Muell. Arg. (Euphorbiaceae) in Brazil.
AB - Lorryia (Tydeinae) species are commonly found in surveys of rubber trees (Hevea
brasiliensis) in Brazil, although only Lorryia formosa (Cooreman, 1958) has been
formally reported from this host. In this study, we described Lorryia
parvireticuli sp. nov., L. amazonensis sp. nov., L. fortistriata sp. nov., and L.
virga sp. nov., associated with rubber trees from Brazil.
PMID- 27615899
TI - Clarification of Einfeldia Kieffer, 1922 (Diptera: Chironomidae) with E.
australiensis (Freeman, 1961), comb. n. based on immature stages.
AB - The immature stages are described for the first time for Chironomus
(Xenochironomus) australiensis Freeman (Diptera: Chironomidae) and the adult male
is redescribed including from type specimens. The species does not belong to
Chironomus Meigen or Xenochironomus Kieffer, but is best placed in a modestly
expanded Einfeldia Kieffer. Application of this genus name is clarified,
including by a lectotype fixation for its type species, E. pectoralis Kieffer,
1924. Einfeldia australiensis (Freeman) comb. n. provides the first record of the
genus from Australia; otherwise the genus is reported confidently only from North
America, Central America and western Europe to Japan. The immature stages of E.
australiensis occur in relatively shallow mesotrophic to eutrophic dune lakes and
maars with circum-neutral pH and high conductivity, from southeastern Queensland
to southern Australia. The cytology is described briefly from larval salivary
glands. Alternative genus placements for the species are discussed, and problems
with Einfeldia and connected systematics in the tribe Chironomini are addressed.
PMID- 27615900
TI - Eusyllinae, Exogoninae and Autolytinae (Syllidae: Polychaeta) from the Southern
Mexican Pacific, with the description of three new species.
AB - Previous studies have dealt recently with syllid polychaetes in soft sediments
from Acapulco Bay (Southern Mexican Pacific) with new species and new records of
the subfamily Syllinae published, but the remaining subfamilies found in the area
had not been included. This study deals with syllids belonging to those
subfamilies: Eusyllinae, Exogoninae and Autolytinae, since the Anoplosyllinae
were not found. Three species are described as new: Odontosyllis septemdentata n.
sp., characterized by having bidentate falcigers and a trepan with 7 teeth
alternating in size; Sphaerosyllis tetralobata n. sp., which is characterized by
having unidentate compound chaetae and segments divided in four annuli, and
Prosphaerosyllis sotoi n. sp., characterized by having compound chaetae with
short and hooked unidentate blades, and by being the only species of the genus
that lacks dorsal cirri in the second parapodia. Additionally, Westheidesyllis
gesae (Perkins 1981) is newly recorded for the Pacific Ocean, while Odontosyllis
fulgurans (Audouin & Milne Edwards 1834), Erinaceusyllis bidentata (Hartmann
Schroder 1974) and Myrianida dentalia (Imajima 1966) are recorded for the first
time from the Mexican Pacific coasts.
PMID- 27615901
TI - The water mite family Aturidae Thor (Acari: Hydrachnidia) from Ghana, with the
description of twelve new species.
AB - Eleven new aturid species are described from Ghana: (Aturinae) Aturus ghanaensis
n. sp., Subaturus spathulasetus n. sp., Subalbia elongata n. sp., (Axonopsinae)
Albaxona wanjakliensis n. sp., Axonopsis kintampo n. sp., Brachypodopsis
indistincta n. sp., Hexaxonopsis rectimarginata n. sp., H. subtruncata n. sp.,
Javalbia coalescens n. sp., J. indentata n. sp., Paraxonopsis latihumerosa n. sp.
and Pseudaxonopsalbia ghanensis n. sp. New records are given for five species of
the genera Albia, Kongsbergia, Paraxonopsis and Subaxonopsalbia.
PMID- 27615902
TI - First records of two flower bug genera from Myanmar (Hemiptera: Heteroptera:
Anthocoridae: Anthocorinae: Oriini), with description of a new species of Bilia.
AB - Two oriine flower bug (Hemiptera: Heteroptera: Anthocoridae) genera, Bilia
Distant, 1904 and Wollastoniella Reuter, 1884 are reported from Myanmar for the
first time, diagnosed, and discussed. A new species, Bilia burma Yasunaga &
Yamada sp. nov., is described, with information on the immature form, habitat and
assumed prey; its closest sister species, B. castanea (Carvalho, 1951), is also
re-diagnosed. Wollastoniella rotunda Yasunaga & Miyamoto, 1993 originally
described from northern Thailand, is also documented along with its immature form
and new host association. Both of the anthocorids found in Myanmar co-occurred
with lace bugs (Tingidae). A checklist of all current members of Bilia and
Wollastoniella is provided. The phylogenic positions of Bilia and Wollastoniella
in the tribe Oriini is discussed.
PMID- 27615903
TI - New species of Pseudachorutes (Collembola: Neanuridae) from Northeastern Algeria.
AB - Three new species of Pseudachorutes are described from the Collo massif in
northeastern Algeria, all three with morphological features unique or rare in the
genus. P. deficiens sp. nov. lacks chaeta E on the labium, a character only
retrieved in P. ouatilouensis Najt & Weiner, 1997 from New Caledonia, from which
it differs by the presence of chaeta a2 on Th. II and of chaeta M on tibiotarsus.
P. octosensillatus sp. nov. is the only species of the genus that have 8 S
chaetae on Ant IV. P. labiatus sp. nov. has 3 x-papillae on the labium, like P.
cf. indiana Christiansen & Bellinger, 1980 from Alaska, from which it differs by
the presence of chaeta a2 on Th. II and a lower number of vesicles in PAO (5-6 vs
10-14).
PMID- 27615905
TI - Descriptions of larvae of four species of Hydropsyche (Hydropsychidae:
Trichoptera) from Thailand.
AB - Morphological characters of the larvae of four species in the genus Hydropsyche
(H. dolosa, H. brontes, H. napaea, and H. camillus) are described and figured for
the first time. The most important diagnostic features are illustrated, and some
information regarding their distribution, biology, and habitat are included.
PMID- 27615904
TI - New species of Rhorus Forster, 1869 (Hymenoptera: Ichneumonidae: Ctenopelmatinae)
from South Korea.
AB - A new ichneumonid-species Rhorus koreensis sp. nov. is described from South
Korea. Monoblastus jinjuensis Lee et Cha, 1993 described from South Korea is
transferred to Rhorus (new combination). Only Rh. takagii (Uchida, 1931) is
recorded previously from South Korea. Rhorus nigritarsis (Hedwig, 1956) is
recorded for the first time from South Korea. A key to the four South Korean
species are provided.
PMID- 27615906
TI - A new Indian species of Pardoteleia Kozlov & Le (Hymenoptera: Scelionidae:
Scelioninae) and first description of the male.
AB - Pardoteleia, a monotypic genus was described by Kozlov and Le (1988). A new
species Pardoteleia flava from India is now described and imaged. The hitherto
unknown male of this genus is also described and imaged for the first time.
Pardoteleia prater, the type species is redescribed and imaged with intraspecific
variations in the Indian specimens.
PMID- 27615907
TI - Revision of the Oriental subfamily Heteropteryginae Kirby, 1896, with a re
arrangement of the family Heteropterygidae and the descriptions of five new
species of Haaniella Kirby, 1904. (Phasmatodea: Areolatae: Heteropterygidae).
AB - The areolate Oriental family Heteropterygidae Kirby, 1893 is critically reviewed
and the results of the present study contradict the arrangement suggested by
Zompro (2004), but in most aspects agree with a molecular study presented by
Whiting et al (2003) and a phylogenetic study presented by Bradler (2009). The
family is critically discussed and new hypotheses are presented for the phylogeny
and intra-familiar relationships, placing the subfamily Dataminae Rehn & Rehn,
1939 as the basalmost clade of Heteropterygidae. The subfamilies Obriminae
Brunner v. Wattenwyl, 1893 and Heteropteryginae Kirby, 1893 together represent
the sister-group of Dataminae. Arguments and a tree are presented to support this
hypothesis. New diagnoses and lists of genera are provided for all three
subfamilies contained in Heteropterygidae, along with keys to distinguish between
them. The subfamily Obriminae is critically reviewed and the distinction between
the three tribes Obrimini Brunner v. Wattenwyl, 1893, Eubulidini Zompro, 2004 and
Miroceramiini Zompro, 2004 introduced by Zompro (2004) is shown to be poorly
supported. While Obrimini sensu Zompro, 2004 is generally accepted (but now also
contains genera that were placed in Eubulidini or Miroceramiini by Zompro
(2004)), the tribes Eubulidini and Miroceramiini are not supported. A new
arrangement is introduced, which is based on morphological characters neglected
or overlooked by Zompro (2004) but were partly discussed by Bradler (2009). The
genus Mearnsiana Rehn & Rehn, 1939 is removed from Miroceramiini and transferred
to Obrimini. The genera Eubulides Stal, 1877, Heterocopus Redtenbacher, 1906,
Theramenes Stal, 1875 and Stenobrimus Redtenbacher, 1906 are removed from
Eubulidini and also transferred to Obrimini. Consequently, Eubulidini is
synonymised with Obrimini (n. syn.). Miroceramiini is a monotypical tribe and
only includes the Wallacean genus Miroceramia Gunther, 1934. The new tribe
Tisamenini n. trib. is established for the three basal genera Tisamenus Stal,
1875, Ilocano Rehn & Rehn, 1939 and Hoploclonia Stal, 1875 all of which were
placed in Eubulidini by Zompro (2004). The latter genus differs from the other
two genera by the morphology of the female genitalia, which is unique amongst the
entire family. Three generic groups are recognized within Obrimini, the Obrimus
group, Stenobrimus-group and Theramenes-group. Keys are presented to distinguish
between the three tribes now contained in the Obriminae, i.e. Obrimini,
Tisamenini n. trib. and Miroceramiini. The genus Hennobrimus Conle, 2006 is
synonymised with Mearnsiana Rehn & Rehn, 1939, based on the fact that the type
species of both genera are conspecific (n. syn.). Hennobrimus hennemanni Conle,
2006, the type-species of Hennobrimus, and Trachyaretaon manobo Lit & Eusebio,
2005 are synonymised with Mearnsiana bullosa Rehn & Rehn, 1939, the type-species
of Mearnsiana (n. syn.). Theramenes dromedarius Stal, 1877 from the Philippines
is removed from synonymy with the Wallacean Theramenes olivaceus (Westwood, 1859)
and re-established as a valid species (rev. stat.). The subfamily
Heteropteryginae Kirby, 1896 is revised at the species-level and a new diagnosis
is presented. Keys to the two genera and all 16 known species are provided along
with new descriptions, differential diagnoses, lists of examined material,
detailed information on the known distributions, measurements and illustrations
of the insects and eggs. The intra-subfamiliar and intra-generic relationships
are discussed and a cladogram is presented. Heteropteryginae contains two genera:
Heteropteryx Gray, 1835 (Type-species: Phasma dilatatum Parkinson, 1798) and
Haaniella Kirby, 1896 (Type-species: Phasma (Heteropteryx) muelleri de Haan,
1842). The distribution of this subfamily is restricted to Sundaland with the
exception of a single species that is found in Vietnam. All other species are
distributed in Borneo, Sumatra, the Mentawai Islands, Singapore, Peninsular
Malaysia and Thailand. Heteropteryginae contains the largest and most striking
members of the entire family Heteropteryginae, some of which are amongst the
heaviest insects known. The subfamily is characterized by apomorphies such as the
presence of wings, having a tympanal area (= stridulatory organ) in the basal
portion of the alae, straight profemora, strongly shortened tarsi, lack of rough
sensory-areas on the prosternum and typically X-shaped micropylar plate of the
eggs. The sister-group of Heteropteryginae is represented by the Obriminae, with
which it shares a beak-like secondary ovipositor in the females and presence of a
medio-apical spine on the area apicalis. Both features are synapomorphies of
Heteropteryginae + Obriminae. The genus Haaniella Kirby, 1904 contains 16 known
species, five of which are newly described herein. The genus Miniopteryx Zompro,
2004 (Type-species: Haaniella parva Gunther, 1944) is synonymised with Haaniella
on the basis that the distinguishing feature mentioned in the original
description is a character that is frequently found throughout the genus (n.
syn.). The type-species H. parva Gunther, 1944 is automatically retransferred to
Haaniella (rev. stat.). Haaniella aculeata n. sp. from western Sumatra is
described from the male. Haaniella macroptera n. sp. from Singapore and the Johor
state in southern Peninsular Malaysia is described from both sexes and the eggs.
Haaniella gintingi n. sp. from Central Sumatra is described from both sexes and
the eggs and Haaniella kerincia n. sp. from Western Sumatra is described from the
insects only, the eggs being still unknown. One new species, Haaniella gorochovi
n. sp., is the only representative of the genus and subfamily Heteropteryginae
known from Vietnam and both sexes as well as the eggs are described. Haaniella
erringtoniae (Redtenbacher, 1906) is endemic in Peninsular Malaysia, here removed
from synonymy with H. muelleri (de Haan, 1842) and re-established as a valid
species (rev. stat.). The Sumatran Haaniella glaber (Redtenbacher, 1906) is
removed from synonymy with H. muelleri (Haan, 1842) and re-established as a valid
species (rev. stat.). Leocrates glaber Redtenbacher, 1906 and Haaniella muelleri
simplex Gunther, 1944 are removed from synonymy with H. muelleri (Haan, 1842)
(rev. stat.) and synonymised with H. glaber. Haaniella mecheli (Redtenbacher,
1906) and H. rosenbergii (Kaup, 1871) are removed from synonymy with H. muelleri
(Haan, 1842) and re-established as valid species (rev. stat.). Haaniella
erringtoniae novaeguineae Gunther, 1934 and Haaniella muelleri var. b. (Haan,
1842) are synonymized with H. rosenbergii (Kaup, 1871) (n. syn.). The type
species Haaniella muelleri (Haan, 1842) is shown to be a fairly rare species that
is restricted to Sumatra. All subsequent records of H. muelleri from outside
Sumatra and references to captive breeding of stock originating from Peninsular
Malaysia in Europe relate to H. erringtoniae (Redtenbacher, 1906). The previously
unknown males and eggs of H. rosenbergii (Kaup, 1871) as well as the previously
unknown females and eggs of H. parva Gunther, 1944 are described and illustrated
for the first time. Based on morphological characters of the insects and eggs
three distinct species-groups are recognized within Haaniella. The muelleri
species-group contains nine species that are distributed throughout Sumatra, the
Mentawei Islands, Singapore and Peninsular Malaysia. These are characterized by
the smooth ventral surface of the meso- and metafemora and lemon-shaped eggs
which entirely lack the setae seen in the two other species-groups. The grayii
species-group comprises four species, two of which are endemic in Borneo, one
endemic in Sumatra and the fourth species being the only known representative of
the subfamily in Vietnam. These species are characteristic for the prominent pair
of spines on the abdominal tergites II-IV of males and long apically multidentate
epiproct of females. The echinata species-group contains three exceptionally
Bornean species, which are characterized by the long and apically pointed
subgenital plate of females, which clearly projects beyond the epiproct, as well
as the sub-basal lateral tooth of the anal segment of males. The muelleri species
group is sister to the remainder two species-groups. Heteropteryx Gray, 1853 is a
monotypical genus and only contains the type-species H. dilatata (Parkinson,
1798), which is found throughout Peninsular Malaysia, Thailand, Sumatra and
Northeastern Borneo. This genus differs from Haaniella by the strongly conically
elevated head, which posteriorly projects over the anterior margin of the
pronotum, females being bright green or yellow in colour with plain and
translucent pink alae and having distinct spines on the abdominal tergites, and
males having a strongly shortened mesothorax and dull pink alae. Lectotypes are
designated for Haaniella parva Gunther, 1944, Heteropteryx echinata Redtenbacher,
1906, Heteropteryx saussurei Redtenbacher, 1906 and Heteropteryx scabra
Redtenbacher, 1906 to guarantee stability of these names. Information on the
habitats, host-plants, biology, life cycle, parasitism and captive breeding of
the species of Heteropteryginae is presented and a list summarising all taxonomic
changes presented herein.
PMID- 27615908
TI - A systematic catalogue of butterflies of the former Soviet Union (Armenia,
Azerbaijan, Belarus, Estonia, Georgia, Kyrgyzstan, Kazakhstan, Latvia, Lituania,
Moldova, Russia, Tajikistan, Turkmenistan, Ukraine, Uzbekistan) with special
account to their type specimens (Lepidoptera: Hesperioidea, Papilionoidea).
AB - A catalogue of butterflies of Russia and adjacent countries is given, with
special account to the name-bearing types depository. This catalogue contains
data about 86 species (3 of them are questionable) of Hesperiidae (22 genera); 47
species of Papilionidae (14 genera); 89 species of Pieridae (5 of them are
questionable) (15 genera); 1 species (1 genus) of Libytheinae(dae); 2 species of
Danainae(dae) (2 genera); 160 species of Nymphalinae(dae) (1 of them is
questionable) (23 genera); 259 species of Satyrinae(dae) (14 of them are
questionable, mainly from genera Oeneis and Pseudochazara) (34 genera); 3 species
of Riodinidae (2 genera); 318 species of Lycaenidae (11 of them are questionable,
mainly from genera Neolycaena and Plebeius) (57 genera). In total: 965 species of
butterflies, 174 genera, by countries: Armenia-244, Azerbaijan-225, Belarus-107,
Estonia-113, Georgia-211, Kyrgyzstan-316, Kazakhstan-344, Latvia-115, Lituania
126, Moldova-87, Russia-522, Tajikistan-295, Turkmenistan-159, Ukraine-192,
Uzbekistan-241. Detailed distribution and subspecific structure (if present) for
every species is provided. Lectotypes of the following species-group taxa are
designated: Hesperia poggei Lederer, 1858, Parnassius felderi Bremer, 1861, P.
eversmanni Eversmann, 1851, P. boedromius Pungeler, 1901, Limenitis moltrechti
Kardakov, 1928, L. sydyi Kindermann, 1853, L. amphyssa Menetries, 1859, L.
doerriesi Staudinger, 1892, L. helmanni duplicata Staudinger, 1892, L. homeyeri
Tancre, 1881, Argynnis penelope Staudinger, 1891, A. thore borealis Staudinger,
1861, Vanessa io geisha Stichel, [1908], Melitaea maturna staudingeri Wnukowsky,
1929 (=uralensis Staudinger, 1871), M. didymina Staudinger, 1895, Papilio
fascelis Esper, 1783, Thecla quercivora Staudinger, 1887, Lycaena orion var.
ornata Staudinger, 1892. The following nomenclatural acts are established:
Neolycaena submontana baitenovi (Zhdanko, 2011), comb. et stat.n. The following
new synonymy is provided: Hesperia comma repugnans (Staudinger, 1892) = lena
Korshunov et Gorbunov, 1995, syn.n.; Argynnis niobe orientalis Alpheraky, 1881
=ornata Staudinger, 1901, syn.n. =tanjusha Zhdanko, 2011, syn.n.; Boloria frigga
gibsoni (Barnes & Benjamin, 1926) = kosarevi Korb, 2011, syn.n., B. erubescens
houri Wyatt, 1961 =ancilla Churkin, 2004, syn.n.; Melitaea fergana maracandica
Staudinger, 1882 = irinae Churkin, Kolesnichenko et Tremasov, 2012, syn.n.; M.
asteroida clara Staudinger, 1887 =ludmilla Churkin, Kolesnichenko et Tuzov, 2000,
syn.n.; Paralasa jordana jordana (Staudinger, 1882) =khramovi Churkin et Pletnev,
2012, syn.n.; P. jordana subocellata (Staudinger, 1901) =kipnisi Churkin et
Pletnev, 2012, syn.n.; P. kusnezovi kusnezovi (Avinov, 1910) =bosbutaensis
Churkin et Pletnev, 2012, syn.n.; Erebia meta Staudinger, 1886 =gertha
Staudinger, 1886, syn.n.; Oeneis ammon ammon Elwes, 1899 =smirnovi Yakovlev,
2011, syn.n.; O. norna tundra A.Bang-Haas, 1912 =ivonini Yakovlev, 2011, syn.n.;
Chazara briseis ianthe (Pallas, 1771) =lyrnessus Fruhstorfer, 1908, syn.n.,
Plebejides stekolnikovi (Stradomsky et Tikhonov, 2015), comb.n.
PMID- 27615909
TI - Revision of the Old World Daphnia (Ctenodaphnia) similis group Cladocera:
Daphniidae).
AB - Species of the genus Daphnia O.F. Muller, 1785 (Cladocera: Daphniidae) have
become very important models in evolutionary biology research. Previous
morphological and genetic evidence suggests that numerous closely related
"species groups" exist within the subgenus Daphnia (Ctenodaphnia) Dybowski &
Grochowski, 1895, containing both described and undescribed species. The Daphnia
similis group is among these species groups. The aim of the present paper is to
revise the taxonomy of the Daphnia (Ctenodaphnia) similis group in the Old World
with both morphological and genetic evidence (based on mitochondrial COI and 12S
rRNA genes). We found that there are at least four species in the Old World D.
similis species group: D. similis Claus, 1876; D. sinensis Gu, Xu, Li, Dumont et
Han, 2013; D. similoides Hudec, 1991 and D. inopinata sp. nov. These four taxa of
the similis-group, confused previously with D. similis, have different
distributional ranges in the Old World, from extremely wide, spanning several
biogegraphic regions (as D. sinensis), to regional endemics (D. similoides) and
even species known so far from a single locality (D. inopinata sp. nov.). The
Daphnia similis group provides another example in the cladocerans whereby the
study of males yields more valuable characters for taxonomy than the study of
parthenogenetic females.
PMID- 27615911
TI - Revision of the Neotropical genus Macreupelmus Ashmead (Hymenoptera:
Chalcidoidea: Eupelmidae).
AB - The Neotropical genus Macreupelmus Ashmead (Eupelmidae: Eupelminae) is revised
based on females, males being unknown for the genus. The genus is redescribed,
its phylogenetic relationships within Eupelminae discussed, and the species
keyed, described and illustrated through macrophotography. Nine species are
recognized-Macreupelmus auranticrus n. sp., M. aurantispina n. sp., M.
brasiliensis Ashmead 1896, M. crassicornis (Cameron 1884), M. dromedarius
(Cameron 1884), M. erwini n. sp., M. granulosus n. sp., M. laticlavius n. sp.,
and M. nigrispina n. sp. Excluded from the genus are Macreupelmus baccharidis
Kieffer 1910 (transferred to Brasema Cameron as B. baccharidis (Kieffer) n.
comb.), Macreupelmus bekilyi Risbec 1952 (transferred to Reikosiella (Hirticauda
Boucek) as Reikosiella (Hirticauda) bekilyi (Risbec) n. comb.), and Macreupelmus
pulchriceps Cameron 1905 (transferred to Eupelmus Dalman as E. (Eupelmus)
pulchriceps (Cameron) n. comb.). The latter name is recognized as the senior
synonym of Cerambycobius cushmani Crawford 1908 n. syn., Cerambycobius townsendi
Crawford 1912 n. syn., and Eupelmus cyaniceps amicus Girault 1916 n. syn.
Lectotypes are designated for M. brasiliensis, M. dromedarius and E. pulchriceps.
PMID- 27615910
TI - Applying n-dimensional hypervolumes for species delimitation: unexpected
molecular, morphological, and ecological diversity in the Leaf-Toed Gecko
Phyllodactylus reissii Peters, 1862 (Squamata: Phyllodactylidae) from northern
Peru.
AB - An integrative taxonomic approach based on morphology, molecular analyses, and
climatic niche modeling was used to uncover cryptic diversity in the
phyllodactylid gecko species Phyllodactylus reissii. At least three distinct
species could be identified among the examined specimens from southern Ecuador
and northern Peru. Phyllodactylus magister, described by Noble (1924) from arid
Andean valleys of the Chinchipe and Maranon rivers in the Peruvian Department of
Cajamarca and synonymized with P. reissii by Dixon & Huey (1970) is elevated from
synonymy and a detailed redescription is provided. A new species of the genus
Phyllodactylus from the Andean dry forest of the southern Maranon valley is
identified and described herein. Phyllodactylus pachamama sp. nov. is
differentiated from other South American congeners on the basis of mtDNA sequence
divergence, morphological characters, and differences in the realized climatic
niche. At least in Peru, P. reissii seems to primarily inhabit the northern
coastal region west of the Andes, while the inter-Andean area along the Rio
Maranon and its tributaries seems to be inhabited mostly by other species of the
genus, which are endemic to this area. The Andean valleys are underestimated in
terms of biodiversity and lack thorough investigation and conservation actions.
PMID- 27615912
TI - A new species of Danothrips from Southwestern China (Thysanoptera: Thripidae).
AB - Danothrips salicis sp. n. is described from young leaves of Salix sp. in
Southwestern China. This species is similar to D. moundi, D. theifolii and D.
trifasciatus, but can be distinguished by the colour of the fore wing, the median
longitudinal split on tergite X of females, and in males by the situation of the
median short thorn-like setae on tergite IX.
PMID- 27615913
TI - Three new replacement names for beetle genera in Cerylonidae, Zopheridae and
Cerambycidae (Insecta: Coleoptera).
AB - This note resolves homonymy among three genera of beetles described by myself
(Slipinski 1988, 1990), John F. Lawrence (Slipinski & Lawrence 1997), and Hermes
E. Escalona (Slipinski & Escalona 2016). I propose new replacement names in
accordance with the International Code of Zoological Nomenclature (ICZN 1999).
Two anonymous reviewers are thanked for making valuable suggestions on an earlier
version of this manuscript.
PMID- 27615914
TI - Two species of Cleonini new for Pakistan and new synonymies Coleoptera:
Curculionidae: Lixinae).
AB - The superfamily Curculionoidea contains over 60,000 described species worldwide
(Oberprieler et al. 2007). Knowledge of their distribution is still incomplete,
with particular regard for several poorly or not yet completely investigated
countries. Moreover, a large number of unidentified specimens of various
geographical origin are conserved in museums throughout the world, and further
unpublished data for many species can be recovered from the study of public and
private collections.
PMID- 27615915
TI - Notes on the geographic variation of Lopinga gerdae Nordstrom, 1934 Lepidoptera,
Nymphalidae, Satyrinae).
AB - Lopinga gerdae Nordstrom, 1934 (Satyrini) is a species geographically restricted
to S. Gansu, Northwest China. It was described from four males and one female
collected from "Ka-tien-kou" on 18.VII.[1930] and "Kung-tze-tagga im Tsaluk-Tal,
Minshan" on 19.VII.[1930] by Dr. David Hummel (Nordstrom, 1934). Though exact
sites could not be located, we were able to confirm that "Ka-tien-kou" and "Kung
tze-tagga" are two small places in a valley of Minshan Mts. in the southwestern
part of the Jone [Choni in Nordstrom (1934)] County. In recent years, specimens
of this species were collected from Tewo by Eckweiler (Gorgner, 1990), from Xiahe
by Bozano (Bozano, 1999), from Daban-shan by Floriani I., Floriani A. and
Saldaitis A. (Bozano pers. comm.), and from Liupan-shan by Chinese researchers.
Specimens from different localities having been compared and their distribution
considered, it is found that this species varies continuously from west to east
in its small range (Fig. 16), with the individuals collected around the type
locality being the intermediate form. However, after dissecting the male
genitalia, the result suggests that the populations from Xiahe and Liupan-shan
should still be regarded as extreme forms of the same species.
PMID- 27615916
TI - A new species of Colobothea Lepeletier & Audinet-Serville, 1825 (Coleoptera:
Cerambycidae: Lamiinae) from Ecuador.
AB - Colobotheini is a tribe of Lamiinae (Cerambycidae) which includes 189 species
classified into 12 genera (Monne, 2016). This tribe is characterized by a
trapezoidal frons, contiguous antennal tubercles, prothorax without lateral
spines, elytra elongate with lateral carina, metatarsomere I elongate and tarsal
claws divaricate (Galileo & Martins, 2006). Colobothea Lepeletier & Audinet
Serville, 1825 is the largest genus of Colobotheini, with 119 valid species
distributed from Mexico to Southern South America, except Chile and latitudes
below 35 degrees S.
PMID- 27615917
TI - Studies of Peruvian Ptiliidae (Coleoptera) 5: Chaska nawi, a new genus and
species of Acrotrichinae, Acrotrichini.
AB - Chaska, a new monotypic genus of Acrotrichinae, Acrotrichini with its single
species nawi is described and figured. Superficially similar to the more rounded
species of Acrotrichis but distinguished by ventral characters in particular the
form of the mesoventral collar and the rounded pronotal hind angles. The insect
was collected by Dr Caroline Chaboo and her students at the University of Kansas
as part of an inventory of leaf beetles in Peru. The name chosen as the winning
entry in a national competition to name a beetle species and raise awareness
about cryptic biodiversity.
PMID- 27615918
TI - Endogean and cavernicolous Coleoptera of the Balkans. XVII. A new species of the
genus Speluncarius Reitter, 1886 (Coleoptera, Carabidae, Harpalinae,
Pterostichini) from Croatia.
AB - The genus Speluncarius Reitter, 1886 (Harpalinae, Pterostichini) is made up by
anophthalmous or almost blind species. The genus is related to Tapinopterus
Schaum, 1858, which contains numerous species from the Balkan-Anatolian region
and have more or less developed eyes. Speluncarius is distributed in the Western
Palaearctic region; 26 species and one subspecies are known from Italy, the
Balkan Peninsula and Turkey. The genus is classified in five subgenera,
Elasmopterus Kraatz, 1886 (6 spp.); Hypogearius Jeannel, 1953 (3 spp.); Hypogium
Tschitscherine, 1900 (1 sp.); Pontotapinus Gueorguiev & Lohaj, 2008 (1 sp.) and
Speluncarius (s.str.) Reitter, 1886 (15 spp.) (Sciaky, 1982; Bousquet, 2003;
Gueorguiev & Lohaj, 2008; Casale et al., 2013).
PMID- 27615919
TI - The lectotype of Goliathus drurii Westwood, 1837 (Coleoptera: Scarabaeidae:
Cetoniinae) in the Macleay Museum, University of Sydney, Australia.
AB - The lectotype of Goliathus drurii Westwood (Coleoptera: Scarabaeidae: Cetoniinae)
has been located to the Macleay Museum, University of Sydney, Australia.
Collected in 1775, this specimen represents the second species of Goliathus to be
illustrated in European literature, however eluding a proper species description
until 1837. This important specimen, overlooked by previous curators, represents
another portion of the Dru Drury collections purchased by Alexander McLeay now
held in the Macleay Museum.
PMID- 27615920
TI - First description of the male of the spider Tibellus paraguensis Simon, 1897
(Araneae: Philodromidae), with new distribution records.
AB - The genus Tibellus Simon, 1875 currently includes 51 species (WSC 2016); it
presents some taxonomic difficulties, due to morphological variability, and
similarities among some congeners (Efimik 1999). Studies on the genus were
undertaken by Gertsch (1933) and Schick (1965) from America, Tikader (1980) from
India, Van den Berg & Dippenaar-Schoeman (1994) from the Afrotropical region, and
Efimik (1999) from the East Palearctic region.
PMID- 27615921
TI - On the taxonomic status of the European Scolelepis (Scolelepis) squamata
(Polychaeta: Spionidae), with description of a new species from southern Europe
On the taxonomic status of the European Scolelepis (Scolelepis) squamata
(Polychaeta: Spionidae), with description of a new species from southern Europe
AB - In order to clarify taxonomic problems relating to the identity of Scolelepis
(Scolelepis) specimens from the Black Sea, the identified material was compared
with specimens of Scolelepis cirratulus (Delle Chiaje, 1829) from the
Mediterranean, of S. squamata (Abildgaard, in O.F. Muller, 1806) from the North
Sea and the Atlantic coast of Spain, and with the syntypes of S. mesnili (Bellan
& Lagardere, 1971) from the Atlantic coast of France. The examination of a large
number of specimens (both juveniles and adults) reveals that the currently
accepted morphological differences distinguishing all species show size-related
patterns, suggesting that they all belong to one species. Therefore, this study
supports the view that Scolelepis cirratulus and Scolelepis mesnili are junior
synonyms of Scolelepis (Scolelepis) squamata. As a result of the re-assessment of
the species limits of Scolelepis (Scolelepis) squamata, a new species, Scolelepis
(Scolelepis) neglecta sp. nov., is distinguished and described from the
Cantabrian coast of Spain. It inhabits shallow sublittoral fine sands and was
earlier misidentified and reported from the Atlantic coast of Europe and the
Mediterranean Sea as Scolelepis squamata, Scolelepis mesnili, Scolelepis cantabra
(Rioja, 1918), or Dispio uncinata Hartman, 1951. The new species is characterized
by having a trilobate prostomium with an acuminate medial portion, a short
peristomium with well-developed dorso-lateral wings, short palps with two
longitudinal bands of elevated lobes, neuropodial postchaetal lamellae notched
from chaetigers 14-41, and strongly curved bidentate neuropodial hooded hooks
with a slight constriction on the shaft starting from chaetigers 19-49. The
morphology, diagnostic characters and ecology of both Scolelepis (Scolelepis)
squamata and Scolelepis (Scolelepis) neglecta sp. nov. are discussed.
PMID- 27615922
TI - Nothocasis rosariae sp. n., a new sylvicolous, montane species from southern
Europe (Lepidoptera: Geometridae, Larentiinae).
AB - In this paper, we describe Nothocasis rosariae sp. n. as the second European
species belonging to the genus Nothocasis Prout, 1937. Differential features from
its allopatric sibling species N. sertata (Hubner, 1817) are presented basing on
wing pattern, morphology of male and female genitalia, and molecular data (COI
barcode region). The type series is designated from southern Italy, but one
examined specimen was collected in Epirus, Greece. The largest phenotypic and
genetic variation was observed in the Pollino Massif, northern Calabria, whilst
the population of the locus typicus in the Sila Massif, central Calabria, appears
to be more homogeneous. 128 individuals were collected in mountainous beech
forests from late August to mid-November. We hypothesize that larvae of N.
rosariae sp. n. feed on Fagus sylvatica whilst those of its sibling species, N.
sertata, feed on Acer.
PMID- 27615923
TI - Two new species of Neocorynura from Guatemala (Hymenoptera: Halictidae:
Augochlorini) with a key to the species known from the country.
AB - This paper describes two new species of bees of the genus Neocorynura Schrottky
from Guatemala. A taxonomic key to all five known species of the genus in
Guatemala is provided and the male of N. centroamericana is described for the
first time.
PMID- 27615925
TI - Colaspis caligula, a new species found in association with Vitis vinifera (L.)
crops in Argentina (Coleoptera: Chrysomelidae).
AB - Some species of Colaspis Fabricius are well-known pests of several crops in
Argentina. In this contribution, we describe a new species within this genus:
Colaspis caligula n. sp., found in association with Vitis vinifera (Linnaeus)
crops. We provide descriptions and illustrations of the mature larva, pupa and
adult, as well as notes on its diagnostic characters, life cycle, and the damages
produced to the plants.
PMID- 27615924
TI - The genus Leucophenga (Diptera, Drosophilidae), part VI: the argentata species
group from the East Asia, with morphological and molecular evidence.
AB - Six species of the Leucophenga argentata species group from East Asia are
examined (including one known and five new ones): L. argentata (de Meijere,
1914); L. bicuspidata sp. nov.; L. fuscivena sp. nov.; L. longipenis sp. nov.; L.
quadricuspidata sp. nov.; L. tricuspidata sp. nov.; the diagnoses for Asian
species of the argentata group and a key to these species are provided. A total
of 44 DNA sequences of the mitochondrial COI (cytochrome c oxidase subunit I)
gene with BOLD process ID and GenBank accession numbers are provided for these
species. The intra- and interspecific pairwise p-distances are summarized. The NJ
(Neighbor-joining) and the Bayesian analyses are used to conduct a molecular
phylogenetic analysis for the above-mentioned species. The molecular data are
used as complementary evidence for the identification of the argentata group
species with sexually dimorphic abdominal tergites.
PMID- 27615926
TI - The extinct river shark Glyphis pagoda from the Miocene of Myanmar and a review
of the fossil record of the genus Glyphis (Carcharhiniformes: Carcharhinidae).
AB - We redescribe an extinct river shark, Glyphis pagoda (Noetling), on the basis of
20 teeth newly collected from three different Miocene localities in Myanmar. One
locality is a nearshore marine deposit (Obogon Formation) whereas the other two
localities represent terrestrial freshwater deposits (Irrawaddy sediments),
suggesting that G. pagoda from the Irrawaddy sediments was capable of tolerating
low salinity like the extant Glyphis. Glyphis pagoda likely reached up to at
least 185 cm in total body length and was probably piscivorous. The fossil
species occurs in rocks of Myanmar and eastern and western India and
stratigraphically ranges at least from the Lower Miocene (Aquitanian) to the
lower Upper Miocene (mid-Tortonian). It has been classified under at least eight
other genera to date, along with numerous taxonomic synonyms largely stemming
from the lack of understanding of the heterodonty in extant Glyphis in the
original description. Our literature review suggests that known Miocene shark
faunas, particularly those in India, are manifested with unreliable taxonomic
identifications and outdated classifications that warrant the need for a
comprehensive taxonomic review in order to evaluate the evolutionary history and
diversity pattern of Miocene shark faunas. The genus Glyphis has a roughly 23
million-year-long history, and its success may be related to the evolution of its
low salinity tolerance. While extant Glyphis spp. are considered to be
particularly vulnerable to habitat degradation and overfishing, the fossil record
of G. pagoda provides renewed perspective on the natural history of the genus
that can be taken into further consideration for conservation biology of the
extant forms.
PMID- 27615927
TI - Bayerotrochus delicatus, a new species of pleurotomariid from Yap Seamount, near
Palau, Western Pacific (Gastropoda: Pleurotomariidae).
AB - A new pleurotomariid species, Bayerotrochus delicatus sp. nov., collected from
the Yap Seamount, near Palau, Western Pacific (8 degrees 51'N, 137 degrees 47'E),
is described and illustrated. The generic assignment is based on morphology and
molecular evidence. The new species is characterized by a small, depressed
trochoid shell sculptured with delicate spiral threads and axial riblets; the
shell surface is lustrous orange mottled with iridescence. The radula has a
formula of R + 3 + 23 + (ca. 30) + (ca. 65) + 9. These features can separate
Bayerotrochus delicatus sp. nov. from its congeners. To determine the
relationships of Bayerotrochus delicatus sp. nov. with other pleurotomariids, a
neighbor-joining (NJ) tree was established using available sequences of
cytochrome c oxidase I gene (COI) from this study and GenBank.
PMID- 27615928
TI - Two new species of nematodes (Nematoda) from highly mineralized rivers of Lake
El'ton basin, Russia.
AB - Two new nematode species, Mesodorylaimus rivalis sp. n. and Allodiplogaster media
sp. n., from the highly mineralized rivers of the El'ton Lake basin (Russia) are
described and illustrated from numerous mature females and males. Mesodorylaimus
rivalis sp. n. is similar to M. vulvapapillatus Bagaturia & Eliava, 1966, but
differs from it in the longer body, shorter spicules and longer female prerectum.
Allodiplogaster media sp. n. resembles A. lupata (Shoshin, 1989) Kanzaki,
Ragsdale & Giblin-Davis, 2014 and A. mordax (Shoshin, 1989) Kanzaki, Ragsdale &
Giblin-Davis, 2014, but differs from the first species in having a shorter
pharynx, shorter outer labial setae, longer spicules and different ratio between
anterior and posterior pharynx sections, and from A. mordax in the thinner body,
shorter pharynx and longer spicules.
PMID- 27615929
TI - New data on Horaeomorphus Schaufuss (Coleoptera: Staphylinidae: Scydmaeninae)
from the Oriental region, with description of a bizarre new species from Yunnan,
Southeast China.
AB - Horaeomorphus bicornis sp. n., a remarkable species with strongly modified head
from Yunnan, Southwest China is described. A distinctly different female from the
same locality is also recorded, its identity remains unconfirmed until associated
males become available. The previously unknown female of H. hujiayaoi Zhou &
Zhang, 2016, is discovered, with its spermatheca and female terminalia
illustrated. Horaeomorphus punctatissimus Franz, 1992 is newly recorded from
Mount Trus Madi, Malaysia. Two females of H. eumicroides Schaufuss, 1889 were
discovered from Singapore, with female terminalia illustrated.
PMID- 27615930
TI - Four new species of the subfamily Gryllacridinae (Orthoptera: Gryllacrididae)
from China.
AB - A taxonomic study of the subfamily Gryllacridinae is presented. Four new species
belonging to two genera are described: Larnaca sinica sp. nov., Larnaca hainanica
sp. nov.; Prosopogryllacris chinensis sp. nov., Prosopogryllacris incisa sp.
nov.. A revised key and distributional data are given.
PMID- 27615931
TI - Review of the genus Haba Semenov, 1954 (Hymenoptera Chrysididae) with the key to
species.
AB - Four species of the genus Haba are reviewed. New combination is proposed for Haba
colonialis (Mocsary, 1911), comb. nov. (from Holopyga). The synonymy between
Holopyga colonialis and Holopyga beaumonti Balthasar, 1953 is not supported. Key
to the species is given.
PMID- 27615932
TI - Ultrastructural observations on the development of Ceratomyxa aegyptiaca
(Myxozoa: Bivalvulida) infecting Solea aegyptiaca (Pleuronectiformes: Soleidae)
from Tunisian coastal lagoon.
AB - Ultrastructural description of Ceratomyxa aegyptiaca Yemmen, Marton, Eszterbauer
and Bahri, 2012 infecting the gallbladder of Solea aegyptiaca Chabanaud, 1927
from a tunisian north-east costal lagoon, was presented in this study. The
primary cell was attached to the gallbladder epithelium and presented at one side
cytoplasmic projections corresponding to pinocytotic invaginations. Netherless,
early sporogonic stages development was carried with contact to the epithelial
cells of gallbladder. Immature spores were identified in early sporoblasts by
their valvogenic, capsulogenic and binucleated sporoplasmic cells. Capsulogenesis
was asynchronous. Each capsulogenic cell presented a large condensed nucleus and
a capsular primordium that extended into an external tube. The eversion and
coiling of the external tube gave rise to the polar filament, which displayed six
turns and an apical plug.
PMID- 27615933
TI - Five new feather mites of the subfamily Pterodectinae (Acariformes: Astigmata:
Proctophyllodidae) from passerines and hummingbirds (Aves) of Brazil.
AB - Five new species of feather mites (Proctophyllodidae: Pterodectinae) are
described from passerines and hummingbirds of Brazil: Amerodectes longifuscus sp.
nov. from Poospiza lateralis (Nordmann, 1835) (Passeriformes: Emberizidae), A.
vireonis sp. nov. from Vireo olivaceus (Linnaeus, 1766) (Passeriformes:
Vireonidae), Tyrannidectes synallaxis sp. nov. from Synallaxis ruficapilla
Vieillot, 1819 (Passeriformes: Furnariidae), Trochilodectes willisi sp. nov. from
Phaethornis eurynome (Lesson, 1832) (Apodiformes: Trochilidae), and Xynonodectes
phaethornis sp. nov. from Ph. pretrei (Lesson & Delattre, 1839) (Apodiformes:
Trochilidae).
PMID- 27615934
TI - A revision of the Neotropical tortoise beetle genus Eurypedus Gistel 1834
(Coleoptera: Chrysomelidae).
AB - The genus Eurypedus Gistel is revised based on detailed morphological study,
including examination of the mouthparts and genitalia. Besides previously known
diagnostic characters, such as an oblong and laterally parallel-sided body,
narrow elytral lamella, narrow prosternal process between the procoxae, and
angled pronotal base, new diagnostic characters are identified: antennal notches
on the ventral surface of antennomeres V-XI, a stridulatory file on the vertex,
and paired projections on the ventral surface of the pronotum. The distinct
stridulatory file is found only in males. The number of ridges of the
stridulatory file varies between 48 and 59. Eurypedus thoni Barber (= Cassida
oblonga Sturm in Thon) syn. nov. is synonymized with E. peltoides (Boheman). The
remaining two species E. peltoides and E. nigrosignatus (Boheman) show distinct
distributions separated by the Amazon Basin.
PMID- 27615935
TI - A new species of Cyphocarididae (Crustacea, Amphipoda, Lysianassoidea) from off
the northeastern Brazilian coast.
AB - This paper describes a species of the genus Cyphocaris Boeck, 1871, the first
record of the family Cyphocarididae Lowry & Stoddart, 1997 from Brazil. Two
specimens, both females, were found in the stomach contents of a tuna caught in
the Saint Peter and Saint Paul Archipelago. The new species is characterized by
coxae 4 and 5 both large, coxa 4 partially overlapping coxae 2-3; coxa of
pereopod 5 with ventral laminar projection and well-developed anteroventral lobe,
broadly rounded and apically folded backwards, basis with anterior margin broadly
rounded and posterior margin with large subacute naked projection (or spur);
uropod 3, outer ramus paddle-shaped; and telson elongate and deeply cleft, with a
nail.
PMID- 27615936
TI - Bodotria jejuensis sp. nov. (Crustacea, Cumacea, Bodotriidae), a new Korean
cumacean.
AB - A new species of Cumacea belonging to the genus Bodotria Goodsir, 1843 was
collected from the Jeju-do Island, Korea. The new speices, Bodotria jejuensis sp.
nov. is similar to B. similis Calman, 1907, B. rugosa Gamo, 1963, B. carinata
Gamo, 1964, and B. biplicata Gamo, 1964 in having a pitted carapace, prominent
dorso-lateral carina, and unarticulated endopod of uropod. However, longish
elliptical shape of carapace, well-developed dorso-lateral carina and distinct
lateral ridge are the major characteristics which serve to distinguish the new
species from its congeners. The new species is fully illustrated and extensively
compared with related species. A key to the Korean Bodotria species is also
provided.
PMID- 27615937
TI - The bees of the genus Colletes Latreille (Hymenoptera: Colletidae) of the
Caucasus region.
AB - Information about bees of the genus Colletes in the Caucasus region is
summarized. Two new species are described from Azerbaijan: Colletes jovel
Kuhlmann & Proshchalykin, sp. nov. and C. longimala Kuhlmann & Proshchalykin, sp.
nov. Nine species are newly recorded from Caucasus: C. asiaticus Kuhlmann 1999,
C. brevigena Noskiewicz 1936, C. cariniger Perez 1903, C. glaber Warncke 1978, C.
idoneus Cockerell 1922, C. inexpectatus Noskiewicz 1936, C. meyeri Noskiewicz
1936, C. schwarzi Kuhlmann 2002, and C. wahrmani Noskiewicz 1959. A total of 50
species are currently known from this area.
PMID- 27615938
TI - A new species of Hyphessobrycon Durbin (Characiformes: Characidae) from rio
Aripuana, rio Madeira basin, Brazil.
AB - A new species of Hyphessobrycon is described from the rio Aripuana, rio Madeira
basin, Amazonas State, Brazil. Hyphessobrycon procyon can be distinguished from
its congeners by the unique combination of the following features: elongation of
the dorsal fin in mature males, absence of dark blotches on the dorsal fin, and
presence of two humeral blotches. The possibility of a relationship of the new
species within H. elachys, H. heliacus, H. loweae, H. moniliger, and H. peugeoti
is discussed based on the sharing of characteristics related to the sexual
dimorphism and tooth morphology.
PMID- 27615939
TI - Cerambycidae (Insecta: Coleoptera) of Quixada, Ceara State, Brazil: new records
and new species.
AB - A checklist of longhorn beetles (Coleoptera, Cerambycidae) of Quixada County,
Ceara State, Brazil is presented. Fifty-six specimens were examined and 32
species were identified, distributed in 29 genera, 19 tribes and two subfamilies.
Fifteen species are new distributional records for Ceara State. Nealcidion
latipenne (Bates, 1863) is recorded by the first time in Caatinga Biome.
Lathroeus immaculatus sp. nov. (Acanthocinini, Lamiinae) is described and
figured.
PMID- 27615940
TI - A new family, genus and species of freshwater amphipod Australomicroprotopus
megacoxa gen. nov. sp. nov. (Senticaudata, Corophiidea, Microprotopoidea,
Australomicroprotopidae fam. nov.) from Australia.
AB - A new species of fresh-water amphipod is described from Australia.
Australomicroprotopus megacoxa gen. nov. sp. nov. It is placed in a new family,
the Australomicroprotopidae fam. nov. and is fully described and figured.
PMID- 27615941
TI - Description of the immature stages and new host plant records of Deois (Deois)
mourei (Berg) (Hemiptera: Cercopidae), a species newly recorded from Argentina
and Paraguay.
AB - Deois (Deois) mourei Cavichioli & Sakakibara (Hemiptera: Cercopidae) is recorded
for the first time from Argentina and Paraguay. The eggs and immature stages of
the species are described and illustrated; the main characters that distinguish
instars are body size, color, number of flagellomeres, and number of tibial and
metatarsomere spines. A key for identification of nymphs of D. (D.) mourei and a
key to differentiate nymphs of the sympatric species D. (D.) mourei and Notozulia
entreriana Berg are provided. In addition, a list of host plants of D. (D.)
mourei in Argentina is given.
PMID- 27615942
TI - Two new species of Diastatotropis Lacordaire (Coleoptera: Anthribidae) from east
Madagascar with a key to species of the genus.
AB - Two new species, Diastatotropis lepidus Tryzna & Banar sp. nov. and
Diastatotropis humeralis Tryzna & Banar sp. nov. (Anthribidae: Anthribinae:
Cappadocini), from Madagascar are described. Colour habitus photographs are
provided. A key to the known species of the genus Diastatotropis is provided.
PMID- 27615943
TI - The Neotropical species of Atractodes (Hymenoptera, Ichneumonidae, Cryptinae),
II: the A. pleuripunctatus species-group.
AB - We describe three new species of parasitoid wasps of the genus Atractodes
(Ichneumonidae: Cryptinae) from South America: A. colchaguensis sp. nov. from
Chile, and A. pleuripunctatus sp. nov. and A. saragurensis sp. nov. from Ecuador.
These species are all characterized by a densely and strongly punctate
mesopleuron. The Atractodes pleuripunctatus species-group is defined to
accommodate the new species. In addition, the second part of the key to species
of the Neotropical Atractodes including this species-group is given.
PMID- 27615944
TI - A new species of hermit crab of the genus Pagurus Fabricius, 1775 (Crustacea:
Anomura: Paguridae) from the southern Caribbean off Venezuela.
AB - A male specimen of a new species of the heterogeneous genus Pagurus Fabricius,
1775, collected in 1968 off the Caribbean coast of Venezuela, was discovered
among the vast crustacean collections of the Smithsonian Institution. This new
species herein described and illustrated is named P. scopaopsis, and is
characterized primarily by the presence of: a brush-like setation pattern on the
dactyl of the left third pereopod, dense small tubercles on the dorsal surfaces
of the dactyl and fixed finger of the right chela, and a raised longitudinal
ridge armed with spines on the palm and fixed finger of the left chela.
PMID- 27615945
TI - A review of the Australian endemic clam shrimp, Paralimnadia Sars 1896
(Crustacea: Branchiopoda: Spinicaudata).
AB - Paralimnadia was recently re-erected to accommodate Australian limnadiids
formally placed in Limnadia. They are characterised by the lack of a spine on the
posterior ventral corner of the telson, a cercopod divided by a spine midlength
into a cylindrical seta bearing basal section and a narrowing denticle bearing
distal section, males amplex females on the posterior body margin keeping the
body in line, and gonochoristic reproduction, so typically sex ratios are broadly
1:1. These characters separate Paralimnadia from the closely related Eulimandia.
Paralimnadia is endemic to and diverse in Australia, and includes the transferred
P. stanleyana (King), P. sordida (King), P. badia (Wolf), P. cygnorum (Dakin) and
P. urukhai (Webb & Bell) as well as 10 new species. All are variable
morphologically, the most conservative characters being the morphology of their
eggs and the cercopod setae. Although found across Australia, there are hot spots
of diversity in the coast and montane areas of New South Wales and southwest of
areas of Western Australia and few in the vast inland arid zone. As in
Eulimnadia, a few occur in rock pools. However those in sandy coastal pools
subject to urbanisation or mining are becoming rare.
PMID- 27615946
TI - Zanobatus maculatus, a new species of panray from the Gulf of Guinea, eastern
central Atlantic (Elasmobranchii: Batoidea: Zanobatidae).
AB - A new species of panray, Zanabatus maculatus sp. nov., is described from 12 type
specimens collected in the Gulf of Guinea (Eastern Central Atlantic). The new
species is distinguished from its sympatric congener, the striped panray
Zanobatus schoenleinii, by its smaller size, heavier thorn pattern, spearhead
shaped dermal denticles and maculate colour pattern.
PMID- 27615947
TI - New cave species of Sinella Brook, 1882 from China (Collembola: Entomobryidae).
AB - Springtails, especially entomobryids, are abundant in Karst faunas. Five new
species of Sinella Brook are described here from caves in southern China: S.
liuae sp. nov., S. hunanica sp. nov., S. tigris sp. nov., S. minuta sp. nov. and
S. tiani sp. nov. A new record of Sinella sineocula Chen & Christiansen, is also
recorded. These species differ in claw structure, chaetae on ventral side of the
head, and body chaetotaxy. An updated key to cave species of Sinella from China
is provided.
PMID- 27615948
TI - Two new species of Mexican Rhinotragini and transference of Odontocera josemartii
Zayas, 1956 to Stenopseustes (Coleoptera, Cerambycidae).
AB - Two new species of Rhinotragini are described from Mexico: Odontocera
argenteolineata; and Stenopseustes transversus. Odontocera josemartii Zayas, 1956
is transferred to Stenopseustes Bates, 1873.
PMID- 27615949
TI - The tadpole of Odontophrynus monachus Caramaschi & Napoli, 2012 (Amphibia, Anura:
Odontophrynidae).
AB - The genus Odontophrynus Reinhardt & Lutken comprises 11 species distributed
throughout South and East of South America (Frost 2016) clustered in three
phenetic groups: O. americanus, O. cultripes, and O. occidentalis (Savage & Cei
1965; Cei 1987; Caramaschi & Napoli 2012). Only the O. occidentalis group is
recovered as monophyletic in the most recent phylogenetic hypotheses (Pyron &
Wiens 2011; Pyron 2014). In these analyses, the O. cultripes group is not
recovered and the monophyly of O. americanus group was not tested, since only one
species of the group was included (Pyron & Wiens 2011; Pyron 2014). Therefore,
the relationships within the genus are still inconclusive due to low support
values and limited taxon sampling.
PMID- 27615950
TI - Taxonomic and morphological studies on the Lygephila dorsigera (Walker, 1865)
species-group, with description of a new species (Lepidoptera, Erebidae,
Toxocampinae).
AB - A new species of the L. dorsigera species-group, Lygephila pallidivena sp. n. is
described. A diagnostic comparison is made with L. dorsigera and Lygephila
lilacina (Butler, 1878). The female genitalia of the holotype of L. dorsigera is
described and illustrated for the first time, and Lygephila kishidai Kinoshita,
1989 is treated here as a junior subjective synonym, syn. n.
PMID- 27615951
TI - Redescription of the poorly known crab spider Xysticus spasskyi (Araneae:
Thomisidae).
AB - With 372 species, Xysticus C.L. Koch, 1835 is the largest genus in the family
Thomisidae (WSC 2016). As with other speciose genera, the genus has never been
revised on a global scale and is only thoroughly known in a few parts of the
Holarctic, namely Central and Northern Europe, North America, Israel and Japan.
Over 200 species are known from one/two taxonomic references only, or from a
single illustrated description/redescription (WSC 2016). The fact that 40% of
species are known from only one sex (104 females and 54 males) or from juveniles
(8 species) (WSC 2016) suggests that Xysticus requires revision. During a study
of crab spiders of the Caucasus, we experienced difficulties in identifying
Xysticus spasskyi Utochkin, 1968 due to the lack of detailed figures of the male
palp and female epigyne. This species was based on the holotype female collected
from an unspecified locality in the coastal part of modern Kransnodar Province
(Utochkin 1968). The male of X. spasskyi was described as X. umbrinus Utochkin,
1968 from Kuban' Region (currently Krasnodar Province). The two species were
synonymised by Ovtsharenko (1979). Besides Krasnodar Province, the species has
been reported from North Ossetia (Ponomarev & Komarov 2013) and South Ossetia
(Ponomarev & Komarov 2015), Georgia, Azerbaijan and the Crimea (Mikhailov 2013;
Otto 2015). The illustrations in the descriptions of Utochkin (1968) and
Ovtsharenko (1979), are either very small, schematic or provide no diagnostic
details. The endogyne (=vulva) of this species has never been illustrated. Here
we redescribe this species and compare distant populations.
PMID- 27615952
TI - Hylaperdina squamosa, a new species of Neotropical Lycoperdininae (Coleoptera,
Endomychidae) from Brazil.
AB - Endomychidae or Handsome Fungus Beetles are a moderately large family of
mycophagous beetles distributed worldwide but with the highest diversity in the
tropics (Shockley et al. 2009a, b). The concept of the family (e.g. Lawrence &
Newton 1995; Tomaszewska 2000, 2010; Shockley et al. 2009a) has recently been
restricted by an elevation of former subfamilies Eupsilobiinae, Mycetaeinae and
Anamorphinae to the level of independent families in the newly recognized
superfamily Coccinelloidea (Robertson et al. 2015).
PMID- 27615954
TI - Description of a new hygrobatid genus from Chile (Acari, Hydrachnidia:
Hygrobatidae).
AB - This paper describes a new genus of the water mite family Hygrobatidae. The
material was collected by V. Stolbov in 2014 and A. Prokin in 2015 in running
waters in Chile. The material was sampled with a common hand net with 250 um mesh
size. The water mites were fixed in 75% ethanol.
PMID- 27615953
TI - Anagrus turpanicus sp. n. (Hymenoptera: Mymaridae) from China, an egg parasitoid
of Arboridia kakogowana (Hemiptera: Cicadellidae).
AB - A new Palaearctic species of Anagrus Haliday (Hymenoptera: Mymaridae), A.
turpanicus Triapitsyn & Hu sp. n., is described and illustrated from Xinjiang
Uyghur Autonomous Region of China. It was reared from parasitized eggs of the
leafhopper Arboridia kakogowana (Matsumura) (Hemiptera: Cicadellidae) (Fig. 10)
on cultivated table grapes from Turpan, which had been previously misidentified
there as Erythroneura apicalis (Nawa) (e.g., Wang et al. 2004, 2011; Luan et al.
2006). This leafhopper has been an important economic pest in Turpan area since
1998, causing serious damage to the cultivated grapevines (Wang et al. 2004; Luan
et al. 2006). Wang et al. (2011) reported that the mite Leptus sp. (Erythraeidae)
and several unidentified spider species were the main natural enemies of
Erythroneura apicalis in and around Turpan. This is the first record of A.
kakogowana from China; it was not included in the key to the Chinese species of
the genus Arboridia Zachvatkin by Song & Li (2015). Arboridia kakogowana is
native to the eastern Palaearctic region (Japan, Korea, and Far East of Russia),
and has been recently recorded as an invasive pest of cultivated grapes in
southern Russia (Gnezdilov et al. 2008).
PMID- 27615955
TI - Whip spiders (Amblypygi, Arachnida) of the Western Palaearctic-a review.
AB - All records of the two amblypygid species occurring in the Western Palaearctic
are mapped and both species (Charinus ioanniticus and Musicodamon atlanteus) are
discussed. Charinus ioanniticus is known from the Eastern Mediterranean (Greece,
Turkey, Israel and Egypt) from 10 localities and Musicodamon atlanteus is known
from the Maghreb (Morocco, Algeria) from three localities. All records are
mapped.
PMID- 27615956
TI - The assassin bug genera Nagustoides and Stenolemus (Hemiptera: Heteroptera:
Reduviidae) newly recorded from Japan.
AB - Two assassin bug genera, Nagustoides Miller, 1954 of Harpactorinae and Stenolemus
Signoret, 1858 of Emesinae (Hemiptera: Heteroptera: Reduviidae), are recorded
from Japan for the first time, with the presence of the representative species N.
lii Zhao, Cai & Ren, 2006 and S. alikakay Redei & Tsai, 2010. Distribution ranges
of the two species are revised by the present finding.
PMID- 27615957
TI - Species-richness in Neotropical Sericothripinae (Thysanoptera: Thripidae).
AB - Two of the three recognized genera of Sericothripinae are known from the
Neotropics, and 14 new species from this area are here described in this
subfamily. Illustrated keys are provided to females of seven species of
Hydatothrips, and 41 species of Neohydatothrips, mainly from Brazil but including
all recorded species south of the border between Mexico and USA. Plant species on
which breeding has been recorded are indicated where possible, notes are provided
on the few species of economic importance, and a key is appended to second instar
larvae of seven species. Neohydatothrips burungae (Hood) stat. rev. and N.
aztecus Johansen stat. rev. are recalled from synonymy with Neohydatothrips
signifer (Priesner), and N. denigratus (De Santis) syn. n. is synonymized with N.
burungae. Hydatothrips williamsi (Hood) comb. n. is relocated from
Neohydatothrips, and as this produces a homonym in the genus, Hydatothrips tareei
nom. nov. is proposed for Hydatothrips williamsi Mound & Tree from Australia.
PMID- 27615958
TI - Complete mitochondrial genome of a Neotropical dobsonfly Chloronia mirifica
Navas, 1925 (Megaloptera: Corydalidae), with phylogenetic implications for the
genus Chloronia Banks, 1908.
AB - The complete mitochondrial (mt) genome of Chloronia mirifica Navas, 1925 was
determined and analyzed. This represents the first mt genome of the Neotropical
endemic dobsonfly genus Chloronia Banks, 1908. The mt genome of C. mirifica is a
typical circular DNA of 15877 base pairs with an A+T 77.1%. It has an ancestral
gene arrangement of the insect mt genome composed of 37 genes. Eleven of the 13
protein coding genes (PCGs) start with ATT and ATG, while nad6 and nad1 start
with ATC and TTG respectively. Five PCGs end with a single T, while the others
have a complete termination codon TAG or TAA. Most tRNAs are folded into the
typical clover-leaf structure except for the trnS1 whose dihydrouridine arm is a
simple loop. The secondary structure of rrnL consists of five structural domains
and 50 helices, while the rrnS includes three domains and 34 helices. The
phylogenetic analysis based on all 13 PCGs and two rRNA genes of the mt genome
recovers Chloronia to be the sister group of Corydalus Latreille, 1802.
PMID- 27615959
TI - Cryptic diversity within the narrowly endemic Lerista wilkinsi group of north
Queensland-two new species (Reptilia: Scincidae).
AB - Herein we describe two new species of the skink genus Lerista from north-eastern
Queensland, based on morphological and genetic data. Additionally, we redescribe
L. cinerea as this species is morphologically more variable than previously
suggested. We allocate these three species to the L. wilkinsi group (Greer et
al. 1983) which is here identified as an endemic Queensland radiation, comprising
L. ameles, L. cinerea, L. hobsoni sp. nov., L. storri, L. vanderduysi sp. nov.,
L. vittata and L. wilkinsi. A number of these species have strong associations
with semi-evergreen vine thickets, listed as an endangered habitat under the
Australian Environment Protection and Biodiversity Conservation Act (1999).
PMID- 27615960
TI - Two deep-sea decapod crustaceans collected off eastern Hokkaido, Japan:
Sclerocrangon rex n. sp. (Caridea: Crangonidae) and Munidopsis verrilli Benedict,
1902 (Anomura: Munidopsidae).
AB - Two species of decapod crustaceans collected from deep sea off eastern Hokkaido,
Japan, are reported. Sclerocrangon rex n. sp. (Caridea: Crangonidae) is described
and illustrated on the basis of material collected off Kushiro and in the Nemuro
Strait at depths of 500-1000 m. It is morphologically similar to S. derjugini
Kobjakova, 1936 and S. igarashii Komai & Amaoka, 1991, both occurring in waters
off eastern Hokkaido, but is easily distinguished from the latter two by the
possession of an extra spine on the postorbital carina on the carapace, located
posterior to the level of hepatic spines. The second, Munidopsis verrilli
Benedict, 1902 (Anomura: Munidopsidae), is the first representative of this squat
lobster family to be recorded from northern Japan. The single specimen of M.
verrilli was collected in the Nemuro Strait off Shiretoko Peninsula at depths of
700-1000 m.
PMID- 27615961
TI - A synopsis of the subgenus Centris (Hemisiella) Moure, 1945 (Hymenoptera: Apidae:
Centridini) in Colombia, with description of a new species.
AB - A synopsis of the species of Centris subgenus Hemisiella Moure in Colombia is
presented. The species included are Centris dichrootricha (Moure), C. facialis
Mocsary, C. merrillae Cockerell, C. tarsata Smith, C. trigonoides Lepeletier and
C. vittata Lepeletier. In addition, C. nebulosa new species from northwestern
Colombia is described, as well as the male of C. merrillae. Diagnoses for both
sexes, occurrence records, and an identification key for the seven species of the
subgenus that occur in the country are provided.
PMID- 27615962
TI - A new species of the lizardfish genus Synodus (Aulopiformes: Synodontidae) from
the western Pacific Ocean.
AB - Synodus pacificus sp. nov., a new species of lizardfish, is described based on
specimens collected in the western Pacific Ocean. It belongs to a species group
with needle-like posterior processes of the pelvic girdle and differs from its
congeners by having the following combination of characters: 4 upside-down omega
shaped marks on the lateral body; black patches on the nape and opercular region;
cross bars on the ventral surface of the head; bars on the dorsal and caudal
fins; orbital large (6.7-8.1% SL); interorbital space narrow (2.1-2.8% SL); snout
short (6.3-7.2% SL); anterior palatine teeth not longer than posterior teeth;
pectoral fin extending slightly beyond a line from base of pelvic fin to origin
of dorsal fin; 7 peritoneal spots; peritoneal membrane pale; nasal flap long and
pointed; dorsal-fin rays 11-13 (mainly11); anal-fin rays 9-11 (mainly 10 or 11);
pectoral-fin rays 11-14 (mainly 12); total vertebrae 53 or 54; pored lateral-line
scales 52-54; transverse scale rows above the lateral line 3.5, below 4.5 or 5;
gill rakers 31-37; and 17-29 teeth on free end of tongue.
PMID- 27615963
TI - Systematic revision of the genus Phaeaphodius Reitter, 1892 (Coleoptera:
Scarabaeidae: Aphodiinae).
AB - The genus Phaeaphodius Reitter, 1892 (Coleoptera: Scarabaeidae: Aphodiinae) is
revised and considered to consist of 12 species. A key to species and diagnosis
of each species are given to fascilitate identification. Lectotypes are
designated for A. costalis Gebler, 1848, A. sibiricus Harold, 1863, A. aeger
Sharp, 1878, and A. solskyi Harold, 1871. Neotypes are designated for A. alleoni
d'Orbigny, 1896, A. fusculus Reitter, 1892, and A. trucantangulus Reitter, 1894.
The name Aphodius fusculus Reitter, 1892 is placed in synonymy with Esymus
pusillus (Herbst, 1789) (new synonymy).
PMID- 27615964
TI - Revised taxonomic status of Eidophasia zukowskyi Amsel, 1938 (Lepidoptera,
Plutellidae) with first description of its male and female genitalia.
AB - We revise the taxonomic status of Eidophasia zukowskyi Amsel, 1938, and we
provide the first descriptions of the genitalia of both sexes. A diagnostic
summary is given with illustrations for a similar congener, Eidophasia syenitella
(Herrich-Schaffer, [1854]).
PMID- 27615965
TI - Cambarus (Jugicambarus) adustus, a new species of crayfish from northeastern
Kentucky delimited from the Cambarus (J.) aff. dubius species complex.
AB - A new species of burrowing crayfish, Cambarus (Jugicambarus) adustus, is
described from Lewis County in northeastern Kentucky, USA. The new species is
most similar morphologically to C. dubius. Cambarus adustus coloration differs
from C. dubius by lacking red, orange and blue hues, and instead is brown over
the entire body surface. Morphological differences between C. dubius and C.
adustus exist in the form I male gonopod, with C. adustus possessing a caudal
knob, while C. dubius does not. In addition, the lateral carapace of C. adustus
is distinctly tuberculate, whereas in C. dubius the carapace lacks extensive
tuberculation. Cambarus (J.) adustus appears to have an extremely small
geographic range (~19.5 km2), and as such we suggest its consideration
for both state and federal levels of protection.
PMID- 27615966
TI - Correction of Cassicinae Bonaparte, 1853 (Aves, Icteridae) to Cacicinae
Bonaparte, 1853.
AB - In our recently published revised classification of the Icteridae (Remsen et al.
2016), we used the family group name Cassicinae Bonaparte, 1853 on the assumption
that its type genus was Cassicus Illiger, 1811. We have since confirmed, after
kind advice from Thomas Donegan (pers. comm. 2016), that Cassicus Illiger (1811:
214) is simply an unjustified emendation of Cacicus Lacepede, 1799, made clear by
Illiger (l.c.) in a footnote to his description of Cassicus. Under Articles
32.5.3.2 and 35.4.2 of the International Code of Zoological Nomenclature (ICZN
1999), a family-group name formed from an unjustified emendation of the name of
its type genus is to be corrected, unless the emendation has come into use as a
substitute name or through prevailing use. This is not the case here, and
accordingly we correct the spelling of Cassicinae to Cacicinae. Bonaparte (1853)
retains authorship; and, although not expressly mentioned before, his originally
ligatured suffix -eoe for the name was automatically corrected by us (Remsen et
al. l.c.) under Articles 11.7.1.3 and 32.5.3 of the Code (ICZN l.c.).
PMID- 27615967
TI - A new species of the spider genus Plator (Trochanteriidae) from south China.
AB - The spider genus Plator Simon (1880) is a small and little-known group in the
spider family Trochanteriidae. Species of Plator are called flat-spiders in
Chinese for the extremely flat habitus (Zhu & Wang 1963). Up to now, 11 Plator
species have been recorded from India, China, Korea and Japan. Six of them, P.
insolens Simon (1880), P. pandeae Tikader (1969), P. pennatus Platnick (1976), P.
sinicus Zhu & Wang (1963), P. yunlong Zhu et al. (2006) and P. bowo Zhu et al.
(2006) are reported from China (World Spider Catalog 2016). Zhu et al. (2006)
suggested two species groups for at least all Chinese Plator species, the P.
insolens group and the P. pennatus group. The former can be recognized by the
absence of RTA of male pedipalp, and the narrow first windings of the copulatory
duct system of female epigyne and the latter, distinguished by the presence of
RTA and the broad first windings of the copulatory duct system.
PMID- 27615968
TI - The second species of Phanoperla (Plecoptera: Perlidae) from China, P. hainana
sp. nov., from Hainan Island.
AB - The genus Phanoperla Banks was originally established as a subgenus of Neoperla
and its genus delimitation was not fully clear until the revisionary work by
Zwick (1982). It currently contains 49 known species from the Oriental region
(Banks 1938, 1939, Cao & Bae 2009, Cao et al. 2007, DeWalt et al. 2016, Jewett
1975, Kawai 1968, Stark 1983, 1987, Stark & Sheldon 2009, Sivec & Stark 2010,
2011, Stark & Sivec 2007, Sivec et al. 1988, Zwick 1982, Zwick 1986, Zwick &
Sivec 1985). Although species of Phanoperla are not rare in many areas of
Southeast Asia bordering China, especially Vietnam and India (Cao & Bae 2009,
Mason & Stark 2015), P. pallipennis Banks, 1938 is the only known species of the
genus known from China. In this paper, we describe a new species of Phanoperla
from Hainan Island of the southernmost province of China. The northern portion of
the island has a humid subtropical climate, whereas the remainder of the island
has tropical monsoon climate.
PMID- 27615969
TI - Vastarena, a new genus for the New Caledonian cicada Abroma pumila Distant
(Insecta: Hemiptera, Cicadoidea, Cicadidae).
AB - In New Caledonia, the species Abroma pumila (Distant, 1892) shows several
incompatibilities with the genus type species A. guerinii (Signoret, 1860). A new
genus, Vastarena, is proposed.
PMID- 27615970
TI - New and little known Orthoptera (Ensifera and Caelifera) from the Nambi River
Natural Reserve, Narino, Colombia.
AB - A preliminary checklist of the Orthopterans from the Nambi River Natural reserve
is presented. A total of 26 species were studied, five new species are herein
described: Championica nambiensis n. sp., Cocconotus awa n. sp., Cocconotus levyi
n. sp. (Tettigoniidae: Pseudophyllinae), Antillicharis kwaiker n. sp. (Gryllidae)
and Brachybaenus nariniensis n. sp. (Gryllacrididae). Three species are recorded
from Colombia for the first time (Legua crenulata, Uvaroviella (Holacla) nebulosa
and Anabropsis alata) and seven species are new records for Narino department
(Allotettix peruvianus, Ripipteryx ecuadoriensis, Neoconocephalus affinis,
Anaulacomera poculigera, Orophus conspersus, Orophus tessellatus and Neocurtilla
hexadactyla). Further comments on species distribution and taxonomy are given.
PMID- 27615971
TI - The bees (Hymenoptera: Apoidea) of the Maltese Islands.
AB - This study presents the first checklist of the bees of the Maltese Islands and
includes notes on the distribution of each species. A total of 95 species
belonging to five bee families are recorded: Andrenidae (17 species), Apidae (34
species), Colletidae (6 species), Halictidae (15 species) and Megachilidae (23
species). Lasioglossum callizonium (Perez, 1896) is recorded for the first time
from the Maltese Islands. Records of three previously reported species are listed
as dubious. The bee fauna of the Maltese Archipelago is dominated by widespread
West-Palaearctic species, and most of the species recorded are also found in the
Western Mediterranean Basin. Bees that have been recorded from Malta are also
known from Southern Europe. The study provides a biogeographical analysis of the
Maltese bee fauna, and discusses the conservation of this group and their
important role in the delivery of ecosystem services in the Maltese Islands.
PMID- 27615972
TI - Description of Panagrellus ulmi sp. n. (Rhabditida, Panagrolaimidae) from Iran,
and comments on the species of the genus and its relatives.
AB - A new species of the genus Panagrellus, P. ulmi sp. n., has been found inside
wetwood cankers of elms from the city of Tabriz, Iran. The new species is
characterized by having small body size (0.91-1.22 mm long in females and 0.82
1.18 mm long in males), lateral field with three longitudinal incisures, lip
region narrowing to distal end with six small lips and oral opening surrounded by
six acute liplets, stoma with gymnostom shorter than cheilostom, cheilorhabdia
not refringent, gymnorhabdia refringent, pharynx with metacorpus not swollen and
isthmus slender, excretory pore at level of metacorpus, ovary very long without
flexures, oviduct swollen, postvulval uterine sac long, 2.0-3.4 times the
corresponding body diameter, both female and male tails conoid-elongate, spicules
with rounded and ventrally bent manubrium and lamina with dorsal anterior hump
and fork-like bifurcate tip, gubernaculum with anterior dorsal handle-like
manubrium, postcloacal genital papillae five pairs, two anterior subventral, one
anterior subdorsal at same level than the first subventral, one posterior
subventral and one posterior subdorsal both at same level. Description,
measurements and illustrations are provided. In addition, species of Panagrellus
and its relatives (Panagrobelus and Plectonchus) are analyzed. After this
analysis, Plectonchus hunti is considered an intermediate species between
Panagrellus and Panagrobelus, and is transferred, based on morphological and
molecular evidence, to the latter genus as Panagrobelus hunti n. comb. On the
other hand, Panagrellus (Panagrellinae) and Baujardia (Baujardinae), are two very
similar genera according to both morphological and molecular evidence; we
consider the respective subfamilies synonyms. Also, Plectonchus and
Anguilluloides show great similarities, which justify considering Anguilluloides
a junior synonym of the former genus. A. procerus is accordingly transferred as
Plectonchus procerus n. comb. while Anguilluloides zondagi is considered a new
junior synonym of Plectonchus molgos. Finally, emended diagnoses of the genera
Panagrellus, Panagrobelus and Plectonchus, compendia, and keys to their species
identification are included.
PMID- 27615973
TI - A new species of Cyrtodactylus (Squamata: Gekkonidae) from Ninh Binh Province,
Vietnam.
AB - We describe a new species of the genus Cyrtodactylus on the basis of six
specimens collected from the limestone forest of the Van Long Wetland Nature
Reserve, Ninh Binh Province, Vietnam. Cyrtodactylus soni sp. nov. can be
distinguished from its congeners by genetic distinction and morphological
differences in number of femoral and precloacal pores, femoral scales, ventral
scales, lamellae, subcaudals, and dorsal tubercle arrangement, as well as in size
and color pattern. In the phylogenetic analyses, the new species is nested in a
clade containing taxa from northwestern and northcentral Vietnam and northern
Laos.
PMID- 27615974
TI - A revision of the myrmecophilous genus Smilax Laporte (Coleoptera: Staphylinidae:
Staphylininae).
AB - The neotropical myrmecophilous genus Smilax is revised and a new species, Smilax
deneinephyto Chatzimanolis is described from southern Brazil. Lectotypes are
designated for Smilax cyanea Wasmann and Staphylinus pilosus Fabricius. Smilax
cyanea is shown to be a junior synonym of Smilax pilosa. A key and illustration
of morphological features are provided for the identification of taxa. The types
of the two species of Smilax were not available for study even though they are
deposited in public museums.
PMID- 27615975
TI - Two new species of genus Joruma McAtee (Hemiptera: Cicadellidae: Typhlocybinae)
from Vicosa, Minas Gerais State, Brazil.
AB - Joruma abernardesi sp.nov. and Joruma phrolfsi sp.nov. (Typhlocybinae: Jorumini)
are described based on specimens from Mata do Paraiso, an Atlantic Forest reserve
located at Vicosa municipality. This is the first record of the genus Joruma
McAtee in Minas Gerais State, southeastern Brazil.
PMID- 27615976
TI - Revision of the spider crab genus Sargassocarcinus Ward, 1936 (Crustacea:
Brachyura: Epialtidae).
AB - The Western Pacific epialtid genus Sargassocarcinus Ward, 1936, is revised. The
genus had been regarded as monotypic but is here shown to contain three species:
S. sublimis (Rathbun, 1916), S. cristatus (Balss, 1924), and S. foliatus Ward,
1936 (type species). The many unusual characters possessed by Sargassocarcinus
are figured and discussed; and diagnostic features of the three species are
clarified. The taxonomy of the three species and aspects of their ecology are
discussed. Sargassocarcinus species are found free-living on coral rubble
habitats and not associated with macrophytic algae.
PMID- 27615977
TI - An annotated checklist of Malachiidae (Coleoptera: Cleroidea) from Iran.
AB - A checklist of Iranian Malachiidae (Coleoptera) is given in this paper. Eighty
two species from 22 genera (subfamily Malachiinae) are listed in the fauna of
Iran. Of these species, 31 are endemic to Iran, and one Anthocomus pupillatus
Abeille de Perrin, 1890 is a new record for this country.
PMID- 27615978
TI - Plateurytion roigi sp. nov., a new geophilid centipede (Myriapoda: Chilopoda:
Geophilomorpha) from Southern Chile.
AB - Plateurytion roigi sp. nov. (Chilopoda: Geophilomorpha: Geophilidae) is fully
described and illustrated from the holotype female from southern Chile (Region X
(de Los Lagos region): Palena province). The new species seems particularly
similar to P. gracilis (Gervais, 1849) (from Chile and Argentina), to which it is
accordingly compared in detail for a confident identification. This is the sixth
report of a species of the genus Plateurytion Attems, 1909, from Chile. The
others are P. gracilis (Gervais, 1849); P. metopias (Attems, 1903); P.
michaelseni (Attems, 1903); P. mundus (Chamberlin, 1955); and P. zapallar
(Chamberlin, 1955). New geographic records are given for Plateurytion mauryi
Pereira, 2008, which is reported for the first time from San Juan province, up to
now only known from the type locality (in Mendoza province), central-western
Argentina. Plateurytion yungarum (Pereira, 2005), is reported from the montane
cloud forest altitudinal level of the Yungas forest of northwestern Argentina,
until now it has only been recorded from the (lowest) montane forest altitudinal
level of the Yungas.
PMID- 27615979
TI - New troglomorphic species of Tomocerus with well-developed postantennal organs
(Collembola: Tomoceridae).
AB - Three new troglobitic species of Tomocerus are described from the southwestern
karsts of China. All of them have well developed postantennal organs. Tomocerus
dong sp. nov. is similar to Tomocerus postantennalis Yu, Zhang & Deharveng and
Tomocerus deharvengi sp. nov., but is different from them mainly in the number of
prelabral chaetae and the dorsal body chaetotaxy. T. deharvengi sp. nov. is very
similar to T. postantennalis but differs from the latter in the cephalic
chaetotaxy, the number of manubrial pseudopores and the number of dental spines.
T. cthulhu sp. nov. is peculiar for the multi-furcated vesicles of ventral tube,
and is different from the three aforementioned species mainly in the dorsal body
chaetotaxy. The position of the new species and the relationships between them
are discussed.
PMID- 27615980
TI - Uncovering the diversity of the neotropical genus Elaphopsocus ('Psocoptera':
Psocidae: Amphigerontiinae): from one to ten species.
AB - For 75 years, the genus Elaphopsocus was considered a monotypic lineage of
neotropical psocids. As a result of recent work in South America, this genus
presently includes seven species from Brazil and Colombia. We here describe three
new species from the East Colombian high Andes.
PMID- 27615981
TI - Larvae of two East-Asian species of Nemoura (Plecoptera: Nemouridae).
AB - Associated larvae of the two East-Asian Nemoura species, N. papilla Okamoto and
N. ussuriensis Zhiltzova are described and illustrated in detail for the first
time. The main diagnostic features of late instar larvae of both species are
color and pigment patterns, the chaetotaxy of the pronotum, legs, abdomen, and
cercal segments.
PMID- 27615982
TI - Three new species of tribe Odynerini (Hymenoptera, Vespidae, Eumeninae) from the
Neotropical Region.
AB - Three new species from the Neotropical region are described: Ancistroceroides
soikai Grandinete & Carpenter, sp. nov. (Costa Rica, Paraguay); Cephalastor
huautla Grandinete & Carpenter, sp. nov. (Mexico), and Symmorphus centralis
Carpenter & Grandinete, sp. nov. (Costa Rica).
PMID- 27615983
TI - Chesklist of gastropod molluscs in mangroves of Khanh Hoa province, Vietnam.
AB - Gastropod molluscs are one of the most important components of mangrove
ecosystem. Mangroves in Central Vietnam have a rather limited distribution due to
peculiarities of the coastline morphology and presently their fauna remains
understudied. Extensive surveys were conducted in both natural vegetation and
artificial mangrove plantations in several localities in Nha Trang Bay from 2005
to 2015. In total 65 species of gastropod molluscs were found alive, 17 of which
can be considered as predominantly mangrove-associated. An illustrated guide is
provided, with short synonymies and data on ecology and distribution. The
recorded molluscan diversity is compared with published data on mangrove
gastropods in different regions of the Indo-Pacific. Total species number and the
proportion of mangrove-associated species are similar to studied faunas in Hong
Kong, Malaysia and Thailand, but the diversity is much lower than that of the
mangal fauna of the Philippines.
PMID- 27615984
TI - A note on Agraeciini species (Orthoptera: Tettigoniidae: Conocephalinae) in
India.
AB - The present paper re-describes three known species of the tribe Agraeciini
(Tettigonidae: Conocephalinae), as well as recording Palaeoagraecia brunnea
Ingrisch, 1998 for the first time from India. These descriptions hold to be
useful in the identification of Indian agraeciine species. The important
morphological characters of the head, pronotum, cerci, spines on the fore tibiae,
hind femora and the ovipositor have been illustrated with suitable line drawings
to distinguish the newly reported species.
PMID- 27615985
TI - Two new genera and five new species of Tullbergiidae (Collembola) from the
southern Appalachian Mountains of North America, with redescription of Tullbergia
clavata Mills.
AB - Two new genera and five new species of Tullbergiidae (Collembola) are described
from the North American Appalachian zone in eastern Tennessee and western North
Carolina. Ameritulla n. gen. is established for species with 15 setae on the
middle tibiotarsus, blunt papilla A on the labial palpus, two long rows of
vesicles in the postantennal organ (PAO), two dorsal sensilla on the third
antennal segment and crescentic pseudocelli. Ameritulla clavata (Mills, 1934) n.
comb. (=Tullbergia clavata Mills, 1934) is designated as type species and
redescribed from type specimens, and A. obscura n. sp. is described. On
Mixturatulla ozwini n. gen., n. sp. papillae A and B of the labial palpus are
thick and blunt, the second row of the PAO is laterally broken into numerous
spherical vesicles, and the dorsum of Abd. VI has two rows of large, coalesced
tubercles. Psammophorura miniclavata n. sp. lacks pseudocelli on the third
abdominal segment, which are present in previously described species.
Stenaphorura shaconage n. sp. is the first species of its genus reliably recorded
from North America. It differs from its Palaearctic relatives in having 2+2
pseudocelli on most body segments. Tullbergia nearctica n. sp. resembles T.
arctica (Wahlgren, 1900) but differs in several chaetotaxic characters.
Sensilliform setae traditionally considered as ordinary pointed setae are
recognized and charted. A new setal nomenclature is proposed for the ventral
setae of the sixth abdominal segment.
PMID- 27615986
TI - Proctolaelaps species (Acari: Mesostigmata: Melicharidae) from Egypt, with
description of a new species and complementary descriptions of other five
species.
AB - The objective of this paper is to provide a taxonomic appraisal of the
melicharids from Egypt, based on specimens previously collected by different
authors and on specimens newly collected by the first author of this paper, all
belonging to the genus Proctolaelaps Berlese. A new species, Proctolaelaps
gizaensis n. sp., is described, thus raising to six the number of Proctolaelaps
species recorded from Egypt. Complementary descriptions of the following species
are also provided: Proctolaelaps aegyptiacus Nasr, 1986; Proctolaelaps
holoventris Moraes, Britto, Mineiro & Halliday, 2016; Proctolaelaps pygmaeus
(Muller, 1859); Proctolaelaps drosophilae Karg, Baker & Jenkinson, 1995 and
Proctolaelaps regalis De Leon, 1963. The latter two species were not found in
Egypt, but they are related to the new species described here. They were re
described based on the type specimens from Europe and North America. A
dichotomous key is given to help the separation of the Proctolaelaps species
concluded to be found in Egypt.
PMID- 27615987
TI - A new canopy-dwelling species of Dendrelaphis (Serpentes: Colubridae) from
Sinharaja, World Heritage Site, Sri Lanka.
AB - A new species of Dendrelaphis, Dendrelaphis sinharajensis sp. nov. is described,
the sixth species of the genus known from Sri Lanka. The new species is readily
distinguished from all other congeners by its colour pattern and scalation. The
species is a canopy-dweller known only from the Sinharaja World Heritage Site and
its vicinity, in the lowland wet zone of Sri Lanka.
PMID- 27615988
TI - Taxonomic note on the oil-collecting bee Centris dimidiata (Olivier, 1789
(Hymenoptera: Apidae: Centridini).
AB - Centris dimidiata (Olivier) is currently considered an easily recognizable
species widely distributed throughout the Amazon basin, mainly in Brazil. For
much of its taxonomic history, C. atriventris Mocsary and C. furcata (Fabricius)
have been considered its junior subjective synonymies. Such interpretation was
apparently due to the lack of a detailed study of the type specimens,
misinterpretation of the original descriptions, and inability to study the
apparently lost type specimen of C. dimidiata. In this paper, a neotype for C.
dimidiata is designated, the species is placed in Centris (Ptilotopus), and C.
denudans rubida Gribodo is proposed as its new junior synonymy. Simultaneously,
as a result of a detailed study of the type material of C. atriventris and C.
furcata, both species are revalidated and their placement in Centris
(Melacentris) is confirmed. For all species, the female is redescribed and the
male is described for the first time. A lectotype for C. atriventris is
designated and new distribution records and a distribution map are provided.
PMID- 27615989
TI - Five new species of genus Encarsia Forster from China (Hymenoptera: Aphelinidae).
AB - Five new species of Encarsia Forster, E. dianensis sp. nov., E. hayati sp. nov.,
E. biseta sp. nov., E. huangi sp. nov., and E. yunnana sp. nov. are described
from China. All share a clear asetose area around the stigmal vein of the fore
wing, and a key to the Chinese species of Encarsia having such a fore wing area
is given based on females. Photomicrographs are provided to illustrate
morphological characters of the new species.
PMID- 27615990
TI - Zorotypus weiweii (Zoraptera: Zorotypidae), a new species of angel insects, from
Sabah, East Malaysia.
AB - A new species of the insect order Zoraptera, Zorotypus weiweii, is described and
figured from Sabah, East Malaysia. The new species represents the second angel
insect from Borneo. Z. caudelli Karny was also collected near the type locality
of Z. weiweii. Methods of specimen collection and a brief note of angel insects
in Malaysia were provided based on new materials and biological observations.
PMID- 27615991
TI - New taxa and notes on some Landrevinae (Orthoptera: Gryllidae) from Malay
Peninsula.
AB - Here, taxonomic notes on species from three genera of bark crickets are
presented. A new locality is recorded for Duolandrevus (Bejorama) parvulus
Gorochov, 2016: Singapore. Two new species of Landrevinae are described: one
species of Endodrelanva Gorochov, 1999 from Singapore: Endodrelanva jimini sp.
nov.; one species of Odontogryllodes Chopard, 1969 from Fraser's Hill, Peninsular
Malaysia: Odontogryllodes gratus sp. nov. The male of Odontogryllodes latus
Chopard, 1969 is also described for the first time and female is redescribed.
Keys to all known species of Endodrelanva and Odontogryllodes is provided.
PMID- 27615992
TI - VARSEDIG: an algorithm for morphometric characters selection and statistical
validation in morphological taxonomy.
AB - We present and discuss VARSEDIG, an algorithm which identifies the morphometric
features that significantly discriminate two taxa and validates the morphological
distinctness between them via a Monte-Carlo test. VARSEDIG is freely available as
a function of the RWizard application PlotsR (http://www.ipez.es/RWizard) and as
R package on CRAN. The variables selected by VARSEDIG with the overlap method
were very similar to those selected by logistic regression and discriminant
analysis, but overcomes some shortcomings of these methods. VARSEDIG is,
therefore, a good alternative by comparison to current classical classification
methods for identifying morphometric features that significantly discriminate a
taxon and for validating its morphological distinctness from other taxa. As a
demonstration of the potential of VARSEDIG for this purpose, we analyze
morphological discrimination among some species of the Neotropical freshwater
family Characidae.
PMID- 27615993
TI - Rhaphium (Diptera: Dolichopodidae: Rhaphiinae) from China with six new species.
AB - There are 26 species of Rhaphium recorded from China, including the following six
species described as new to science: Rhaphium apophysatum sp. nov., R. bilobum
sp. nov., R. bisectum sp. nov., R. daqinggouense sp. nov., R. dorsiseta sp. nov.,
R. neimengense sp. nov. Two new groups: the R. flavilabre and R. bilobum species
groups are proposed. A key to the species of Rhaphium from China is provided.
PMID- 27615994
TI - A new genus of predatory katydids (Orthoptera: Tettigoniidae: Listroscelidinae)
from the Amazonian Rainforest.
AB - Most of the predatory katydids Listroscelidini species known were described from
the Brazilian Atlantic Forest. Here a new genus and species from the Amazonian
Rainforest is described. Based on its morphological characteristics, this new
genus represents an intermediate form between two closely related genera,
Listroscelis Serville and Monocerophora Walker.
PMID- 27615995
TI - Study of stability and biophysical characterization of ranibizumab and
aflibercept.
AB - The anti-vascular endothelial growth factor (VEGF) agents such as ranibizumab
(Lucentis(r)) and aflibercept (EyLea(r)) are currently used as monthly or
bimonthly intravitreal injections to treat potentially retinal diseases such as
wet age-related macular degeneration (AMD) or diabetic macular edema (DME).
Because of the complications associated with repeated intra-vitreal injections,
there is considerable interest in developing a sustained delivery system. The
purpose of this study was to examine the stability of both therapeutic proteins
under physiological conditions as well as when incorporated into drug delivery
systems (DDS). First, thermotropic properties in physiological conditions and at
different pH values were evaluated by differential scanning calorimetry (DSC) to
determine the protein denaturation temperature. Second, the effects of pH and
incubation time on conformational changes and aggregation were evaluated by
circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, and
size-exclusion chromatography (SEC). Also, the ability of both proteins to bind
to VEGF was tested in the aforementioned experimental conditions for up to 30
days. Finally, we investigated the stability of both proteins after a rapid
screening method that simulates the first homogenizing step during the protein
microencapsulation process. This method allowed the development of stable
ranibizumab and aflibercept formulations that may be useful to entrap these
proteins into microparticles selecting the most convenient organic solvent and
protein stabilizers.
PMID- 27615996
TI - Preactivated thiomers for intranasal delivery of apomorphine: In vitro and in
vivo evaluation.
AB - The purpose of this study was to synthesize preactivated thiomers with different
degrees of preactivation and to evaluate their potential as novel excipient for
nasal apomorphine administration. The thiomer (PAA-cys) was synthesized by
addition of thiol groups on poly(acrylic acid) with various molecular mass
including 100, 250and450kDafollowed by immobilization of 2-mercaptonicotinic acid
(2MNA) to thiol groups by disulfide bond formation resulting in PAA-cys-2MNA.
These thiomers (PAA100-cys, PAA250-cys and PAA450-cys) were in the next step
preactivated by 56.3, 59.5 and 46.5% (medium degree), and 80.1, 81.6 and 87%
(high degree), respectively. Apomorphine permeation across porcine nasal mucosa
in the presence of PAA100-cys-2MNA, PAA250-cys-2MNA and PAA450-cys-2MNA with high
degree of preactivation was 3.1-, 4.4- and 4.1-fold, while 2.7-, 3.4- and 3.0
fold higher than control for medium degree of preactivation, respectively.
Administration of apomorphine in the presence of PAA250-cys-2MNA showed in rats 9
and ~2-fold improvement of relative bioavailability compared with oral and
intranasal administration of apomorphine solution, respectively. Because of the
pronounced improvement among other polymers, PAA250-cys-2MNA with high degree of
preactivation could be considered as promising excipient for nasal delivery of
apomorphine.
PMID- 27615997
TI - Controlled release ibuprofen-poloxamer gel for epidural use - A pharmacokinetic
study using microdialysis in pigs.
AB - In order to avoid the risks of sideeffects of epidural local anesthetics and
opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally
would be an interesting option of analgesic therapy. The fairly short duration of
action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by
using controlled release poloxamer gel formulation. Using a microdialysis
technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen
after its epidural administration as a poloxamer 407 formulation or a solution
formulation. In addition, plasma ibuprofen concentrations were analyzed from
central venous blood samples. Ibuprofen concentrations in the epidural space were
significantly higher and longer lasting after the epidural gel injection compared
with the epidural solution injection. The epidural AUC of ibuprofen was over
threefold greater after epidural ibuprofen gel injection compared with the
ibuprofen solution injection (p<0.001). The systemic absorption of ibuprofen from
25% poloxamer 407 gel was very low. The in situ forming poloxamer gel acted as a
reservoir allowing targeted ibuprofen release at the epidural injection site and
restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from
the epidural space to the intrathecal space was steady and prolonged. These
results demonstrate that the use of epidurally injectable poloxamer gel can
increase and prolong ibuprofen delivery from epidural space to the CSF enhancing
thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further
toxicological and dose-finding studies are justified.
PMID- 27615998
TI - Spillover Events of Infection of Brown Hares (Lepus europaeus) with Rabbit
Haemorrhagic Disease Type 2 Virus (RHDV2) Caused Sporadic Cases of an European
Brown Hare Syndrome-Like Disease in Italy and Spain.
AB - Rabbit haemorrhagic disease virus (RHDV) is a lagovirus that can cause fatal
hepatitis (rabbit haemorrhagic disease, RHD) with mortality of 80-90% in farmed
and wild rabbits. Since 1986, RHDV has caused outbreaks in rabbits (Oryctolagus
cuniculus) in Europe, but never in European brown hares (Lepus europaeus, EBH).
In 2010, a new RHDV-related virus, called RHDV2, emerged in Europe, causing
extended epidemics because it largely overcame the immunity to RHDV present in
most rabbit populations. RHDV2 also was identified in Cape hare (Lepus capensis
subsp. mediterraneus) and in Italian hare (Lepus corsicanus). Here, we describe
two distinct incidents of RHDV2 infection in EBH that occurred in Italy (2012)
and Spain (2014). The two RHDV2 strains caused macroscopic and microscopic
lesions similar to European brown hare syndrome (EBHS) in hares, and they were
genetically related to other RHDV2 strains in Europe. EBHs are common in Europe,
often sharing habitat with rabbits. They likely have been exposed to high levels
of RHDV2 during outbreaks in rabbits in recent years, yet only two incidents of
RHDV2 in EBHs have been found in Italy and Spain, suggesting that EBHs are not a
primary host. Instead, they may act as spillover hosts in situations when
infection pressure is high and barriers between rabbits and hares are limited,
resulting in occasional infections causing EBHS-like lesions. The serological
survey of stocked hare sera taken from Italian and Spanish hare populations
provided an understanding of naturally occurring RHDV2 infection in the field
confirming its sporadic occurrence in EBH. Our findings increase the knowledge on
distribution, host range and epidemiology of RHDV2.
PMID- 27615999
TI - Observations of internal flow inside an evaporating nanofluid sessile droplet in
the presence of an entrapped air bubble.
AB - Using a unique, near-field microscopy technique, fringe patterns and nanoparticle
motions are visualized immediately following a nanofluid droplet deposition on a
glass substrate in which an air bubble is entrapped. The nanofluid consists of DI
water, 0.10% Aluminum Oxide nanoparticles with an average diameter of 50 nm, and
0.0005% yellow-green polystyrene fluorescent particles of 1 MUm diameter. High
speed, fluorescent-mode confocal imaging enables investigation of depth-wise
sectioned particle movements in the nanofluid droplet inside which a bubble is
entrapped. The static contact angle is increased when a bubble is applied. In the
presence of the bubble in the droplet, the observed flow toward the center of the
droplet is opposite to the flow observed in a droplet without the bubble. When
the bubble is present, the evaporation process is retarded. Also, random motion
is observed in the contact line region instead of the typical evaporation-driven
flow toward the droplet edge. Once the bubble bursts, however, the total
evaporation time decreases due to the change in the contact line characteristics.
Moreover, the area of fringe patterns beneath the bubble increases with time.
Discussed herein is a unique internal flow that has not been observed in
nanofluid droplet evaporation.
PMID- 27616000
TI - Combination of Thiol-Additive-Free Native Chemical Ligation/Desulfurization and
Intentional Replacement of Alanine with Cysteine.
AB - We report a novel strategy for native chemical ligation (NCL). Alanines not
located at a ligation site are temporarily replaced with cysteines, and this
enables efficient thiol-additive-free NCL, with subsequent desulfurization to
regenerate the target peptide. We synthesized stresscopin-related peptide and
neuroendocrine regulatory peptide-2 (NERP-2) by this method. We confirmed that
both conventional alkyl thioester and thioester-equivalent N-acyl-N'-methyl
benzimidazolinone (MeNbz) can be adopted as thioester components for thiol
additive-free NCL of multi-Cys-containing peptides.
PMID- 27616001
TI - Top-100 cited articles on Guillain-Barre syndrome: a bibliometric analysis.
AB - Since the first description of Guillain-Barre syndrome (GBS) 100 years ago, the
concept of this syndrome has changed remarkably. The purpose of our study was to
identify and characterize the most-cited articles that have contributed to
advancing the understanding of GBS. Based on the database of Journal Citation
Reports, we selected 554 journals that were considered as potential sources of
reports on studies related to clinical neurology and general medicine. The Web of
Science search tools were used to identify the most-cited articles relevant to
GBS or other variants in the selected journals. Of the selected articles, 18 were
review articles and the remainder were original articles or included only a few
case series. Among the original articles, 13 described basic research associated
with immunological pathogenesis involving anti-ganglioside antibodies. Most of
the original studies (42/64, 66%) published after 1990 evaluated anti-ganglioside
antibodies that mediated axonal GBS or Miller Fisher syndrome, with only a small
number of the papers involving electrodiagnostic medicine (n = 4). Our
bibliometric analysis has yielded a detailed list of the top-100 cited articles
in the field of GBS.
PMID- 27616002
TI - Is Emotion Regulation the Path to Remission for Late-Life Depression?
PMID- 27616003
TI - Intra-articular tibial plateau fracture characteristics according to the "Ten
segment classification".
AB - BACKGROUND: Currently existing classifications of tibial plateau fractures do not
help to guide surgical strategy. Recently, a segment-based mapping of the tibial
plateau has been introduced in order to address fractures with a fracture
specific surgical approach. The goal of the present study was to analyze
incidence and fracture specifics according to a new 10-segment classification of
the tibial plateau. METHODS: A total of 242 patients with 246 affected knees were
included (124 females, 118 males, mean age 51.9+/-16.1years). Fractures were
classified according to the OTA/AO classification. Fracture pattern was analyzed
with respect to a 10-segment classification based on CT imaging of the proximal
tibial plateau 3cm below the articular surface. RESULTS: 161 Patients suffered an
OTA/AO type 41-B and 85 patients an OTA/AO type 41-C tibial plateau fracture.
Females had an almost seven times higher risk to suffer a fracture due to low
energy trauma (OR 6.91, 95% CI (3.52, 13.54), p<0.001) than males. In 34% of the
patients with affection of the medial tibial plateau, a fracture comminution,
primarily due to low-energy trauma (p<0.001), was observed. In type B fractures,
the postero-latero-lateral (65.2%), the antero-latero-lateral (64.6%) and the
antero-latero-central (60.9%) segment were most frequently affected. Every second
type C fracture showed an unique fracture line and zone of comminution. The
tibial spine was typically involved (89.4%). A typical fracture pattern of high
energy trauma demonstrated a zone of comminution of the lateral plateau and a
split fracture in the medial plateau. The most frequently affected segments were
the postero-latero-central (85.9%), postero-central (84.7%), and antero-latero
central (78.8%) segment. CONCLUSION: Posterior segments were the most frequently
affected in OTA/AO type B and C fractures. Acknowledging the restricted
visibility of posterior segments, whose reduction and fixation is crucial for
long-term success, our findings implicate the use of posterior approaches more
often in the treatment of tibial plateau fractures. Also, low-energy trauma was
identified as an important cause for tibial plateau fractures.
PMID- 27616004
TI - Integrated risk scoring model for predicting dynamic hip screw treatment outcome
of intertrochanteric fracture.
AB - BACKGROUND: Dynamic hip screw (DHS) is a common device for treating
intertrochanteric fracture (ITF). Various risk factors have been reported to be
associated with the operative treatment outcome. However, an integrated risk
scoring prediction model is lacking. In this study, we aimed to develop a
prediction model for treatment outcome of intertrochanteric fracture. METHODS: We
analyzed 442 AO/OTA 31-A1 and A2 fractures which were treated with DHS during the
period January 2000 to June 2014 in a level I trauma center. Risk factors
including age, gender, injured side, lag screw position, AO/OTA classification,
tip-apex distance, postoperative lateral wall fracture, reduction patterns were
analyzed to determine their influence on treatment outcome. Integrated risk
scores of significant predictors were used to construct a prediction model.
RESULTS: AO/OTA 31-A2 classification, postoperative lateral wall fracture,
posteriorly inserted lag screw and varus reduction pattern were significant risk
predictors for DHS failure. The failure risk for low- and high-risk groups were
significantly different (P<0.001) CONCLUSION: AO/OTA 31-A2 classification,
postoperative lateral wall fracture, posteriorly inserted lag screw and varus
reduction pattern were significant risk predictors for DHS failure. We developed
a model that integrates these factors to predict the treatment outcome, which had
excellent prediction accuracy and discriminatory ability. The models may provide
useful information for orthopedic doctors to identify patients who need early
intervention as well as ITF patients who require more frequent follow-up in the
postoperative period.
PMID- 27616005
TI - Psychological distress following a motor vehicle crash: A systematic review of
preventative interventions.
AB - INTRODUCTION: Psychological distress following a motor vehicle crash (MVC) is
prevalent, especially when the person sustains an associated physical injury.
Psychological distress can exhibit as elevated anxiety and depressive mood, as
well as presenting as mental disorders such as Post Traumatic Stress Disorder
(PTSD) or Major Depressive Disorder (MDD). If unmanaged, psychological distress
can contribute to, or exacerbate negative outcomes such as social disengagement
(e.g., loss of employment) and poor health-related quality of life, as well as
contribute to higher costs to insurers. This systematic review summarises current
research concerning early psychological intervention strategies aimed at
preventing elevated psychological distress occurring following a MVC. METHOD: A
systematic review of psychological preventative intervention studies was
performed. Searches of Medline, Embase, PsychINFO, Web of Science and Cochrane
Library were used to locate relevant studies published between 1985 and September
2015. Included studies were those investigating MVC survivors who had received an
early psychological intervention aimed at preventing psychological distress, and
which had employed pre- and post- measures of constructs such as depression,
anxiety and disorders such as PTSD. RESULTS: Searches resulted in 2608 records.
Only six studies investigated a psychological preventative intervention post-MVC.
Interventions such as injury health education, physical activity and health
promotion, and therapist-assisted problem solving did not result in significant
treatment effects. Another six studies investigated psychological interventions
given to MVC survivors who were assessed as sub-clinically psychologically
distressed prior to their randomisation. Efficacy was varied, however three
studies employing cognitive behaviour therapy (CBT) found significant reductions
in psychological distress compared to wait-list controls. CONCLUSION:
Psychological interventions aimed at preventing psychological distress post-MVC
are limited, often involving small samples, with subsequent poor statistical
power and subsequent high risk of bias. These factors make it difficult to draw
conclusions, however CBT appears encouraging and therefore worthy of
consideration as a preventative intervention.
PMID- 27616006
TI - A negative association between bromadiolone exposure and nestling body condition
in common kestrels: management implications for vole outbreaks.
AB - BACKGROUND: Vole outbreaks have been extensively described, along with their
impacts on humans, particularly in agricultural areas. The use of rodenticides is
a common legal practice to minimise crop damage induced by high vole density for
biocidal use. However, rodenticides can have negative direct and indirect impacts
on non-target species that feed on voles. We studied whether the use of a second
generation anticoagulant rodenticide (SGAR), bromadiolone, can be detected in the
blood of fledglings of wild common kestrels Falco tinnunculus in two areas of
central Spain, exploring its possible indirect effects. RESULTS: We found that
16.9% of fledglings had a detectable concentration of bromadiolone in their
blood, with an average concentration of 0.248 +/- 0.023 ng mL-1 . Fledglings with
bromadiolone in their blood, regardless of the concentration, had 6.7% lower body
mass than those without detectable bromadiolone. CONCLUSION: The use of
bromadiolone was detectable in the blood of alive non-target species. Detected
bromadiolone in blood may reduce the body condition of nestlings, potentially
reducing their fitness. The source of bromadiolone found in nestlings needs to be
determined in future studies to derive accurate management advice. However, we
urge the discontinuation of official SGAR distribution to farmers and their use
in agrarian lands to minimise damage of voles on crops, particularly where common
kestrels breed, and encourage the use of alternative effective practices. (c)
2016 Society of Chemical Industry.
PMID- 27616007
TI - Development of a quantitative method for active epidermal growth factor extracted
from dissolving microneedle by solid phase extraction and liquid chromatography
electrospray ionization mass spectrometry.
AB - Dissolving microneedle (DMN), a transdermal drug delivery in which biological
drugs are encapsulated in biodegradable and biocompatible polymers, was
fabricated using epidermal growth factor (EGF) as a model drug and hyaluronic
acid (HA) as a backbone polymeric matrix. After mixing calibration and DMN
samples with insulin, an internal standard, solid phase extraction (SPE) was
performed to separate EGF and insulin from HA, and then liquid chromatography
electrospray ionization mass spectrometry (LC-ESI-MS) was conducted for microgram
scale quantitation. The method showed good linearity (R2=0.997) within a
specified range (1-4MUg). Additionally, the decrease in EGF levels during DMN
fabrication was compared using the SPE/LC-ESI-MS and enzyme-linked immunosorbent
assay (ELISA), a traditional analytical method. The ELISA method detected an EGF
loss of only 3.88+/-4.67%, whereas SPE/LC-ESI-MS detected a loss of 16.75+/
4.39%. Qualitative analysis by circular dichroism showed wavelength shift and
splitting after DMN fabrication indicating that EGF was denatured during DMN
fabrication and cell viability test showed SPE/LC-ESI-MS is more accurate and
reliable for detecting the amount of active EGF loaded into the DMN than ELISA.
PMID- 27616008
TI - Simultaneous determination of estrogens and progestogens in honey using high
performance liquid chromatography-tandem mass spectrometry.
AB - This work describes the development and validation of a method for the
simultaneous determination of 13 estrogens and progestogens in honey by high
performance liquid chromatography-tandem mass spectrometry. The hormones were
preconcentrated by solid phase extraction. Pretreatment variables were optimized
for a better compatibility with electrospray ionization interfaced mass
spectrometry. The analytes were analyzed in multiple-reaction monitoring mode
with two pairs of precursor product ion transitions. The proposed method was
validated with method detection limits of 0.01-0.33ng/g and good linearities
(r2>0.9901) throughout the studied concentration range. The recoveries of
analytes at the spiking levels (5ng/g and 25ng/g) ranged from 71.2% to 99.7%,
with relative standard deviations below 20%. The method was used to determine the
target compounds in honey samples (orange blossom, clover and multiflower)
obtained from supermarkets. Two samples of honey were found to contain trace
amounts of estrone (=80)
on treatment and surgical outcome of colorectal cancer. METHOD: In the period
between October 1995 and April 2014, a total of 1397 patients underwent emergency
and elective surgical interventions for CRC; the first group (Group-Older - GO)
was composed of 291 patients 80 years or older (20.9%, of which 46.4% were male).
The second group (Group-Younger - GY) included 1106 patients younger than 80
years (79,1%, 57.7% males). RESULTS: Significant differences between the two
groups were observed regarding sex (p = 0.001), number of comorbidities (p =
0.001), ASA classification (p < 0.001), emergency presentation (p < 0.001), site
of tumor (p = 0.010), need of intraoperative blood transfusions (p < 0.001), 30
days mortality (p < 0.001), 90-days mortality (p < 0.001) and morbidity in
accordance with Clavien-Dindo classification (p < 0.001). When combining both
elective and emergency procedures, multivariate logistic regression analysis
showed that advanced age (>=80 years old) was an independent predictor factor of
30-days mortality (p = 0.023, OR = 2.23) and morbidity (p = 0.088, OR = 1.31),
while it was not predictive of 90-days mortality. When considering only elective
colorectal surgery, octogenarian age was not found to be a predictive factor of
30-day and 90-day mortality, but predictive of postoperative morbidity.
CONCLUSION: Old age (>=80) does not represent a contraindication to CRC elective
surgical treatment, in emergency procedures it is associated with an increased
risk of postoperative morbidity and mortality.
PMID- 27616060
TI - Erratum to: Pomalidomide mitigates neuronal loss, neuroinflammation, and
behavioral impairments induced by traumatic brain injury in rat.
PMID- 27616061
TI - Type VI Secretion System Substrates Are Transferred and Reused among Sister
Cells.
AB - Bacterial type VI secretion system (T6SS) is a nanomachine that works similarly
to a speargun. Rapid contraction of a sling (sheath) drives a long shaft (Hcp)
with a sharp tip and associated effectors through the target cell membrane. We
show that the amount and composition of the tip regulates initiation of full
length sheath assembly and low amount of available Hcp decreases sheath length.
Importantly, we show that both tip and Hcp are exchanged by T6SS among by
standing cells within minutes of initial cell-cell contact. The translocated
proteins are reused for new T6SS assemblies suggesting that tip and Hcp reach the
cytosol of target cells. The efficiency of protein translocation depends on
precise aiming of T6SS at the target cells. This interbacterial protein
complementation can support T6SS activity in sister cells with blocked protein
synthesis and also allows cooperation between strains to increase their potential
to kill competition. VIDEO ABSTRACT.
PMID- 27616063
TI - Isolation of atropine and scopolamine from plant material using liquid-liquid
extraction and EXtrelut(r) columns.
AB - Tropane alkaloids are toxic secondary metabolites produced by Solanaceae plants.
Among them, plants from Datura genus produce significant amounts of scopolamine
and hyoscyamine; the latter undergoes racemization to atropine during isolation.
Because of their biological importance, toxic properties and commonly reported
food and animal feed contamination by different Datura sp. organs, there is a
constant need for reliable methods for the analysis of tropane alkaloids in many
matrices. In the current study, three extraction and sample-clean up procedures
for the determination of scopolamine and atropine in plant material were compared
in terms of their effectiveness and repeatability. Standard liquid-liquid
extraction (LLE) and EXtrelut(r) NT 3 columns were used for the sample clean-up.
Combined ultrasound-assisted extraction and 24h static extraction using ethyl
acetate, followed by multiple LLE steps was found the most effective separation
method among tested. However, absolute extraction recovery was relatively low and
reached 45-67% for atropine and 52-73% for scopolamine, depending on the compound
concentration. The same method was also the most effective one for the isolation
of target compounds from Datura stramonium leaves. EXtrelut(r) columns, on the
other hand, displayed relatively low effectiveness in isolating atropine and
scopolamine from such a complex matrix and hence could not be recommended. The
most effective method was also applied to the extraction of alkaloids from roots
and stems of D. stramonium. Quantitative analyses were performed using validated
method based on gas chromatography with flame ionization detector (GC-FID). Based
on the results, the importance of the proper selection of internal standards in
the analysis of tropane alkaloids was stressed out.
PMID- 27616064
TI - Effect of surfactants on surface activity and rheological properties of type I
collagen at air/water interface.
AB - We describe the effect of three synthetic surfactants (anionic - sodium dodecyl
sulfate (SDS), cationic - cetyltrimethylammonium bromide (CTAB) and nonionic -
Triton X-100 (TX-100)) on surface properties of the type I calf skin collagen at
the air/water interface in acidic solutions (pH 1.8). The protein concentration
was fixed at 5*10-6molL-1 and the surfactant concentration was varied in the
range 5*10-6molL-1-1*10-4molL-1, producing the protein/surfactant mixtures with
molar ratios of 1:1, 1:2, 1:5, 1:10 and 1:20. An Axisymmetric Drop Shape Analysis
(ADSA) method was used to determine the dynamic surface tension and surface
dilatational moduli of the mixed adsorption layers. Two spectroscopic techniques:
UV-vis spectroscopy and fluorimetry allowed us to determine the effect of the
surfactants on the protein structure. The thermodynamic characteristic of the
mixtures was studied using isothermal titration calorimetry (ITC) and
differential scanning calorimetry (DSC). Modification of the collagen structure
by SDS at low surfactant/protein ratios has a positive effect on the mixture's
surface activity with only minor deterioration of the rheological properties of
the adsorbed layers. The collagen/CTAB mixtures do not show that pronounced
improvement in surface activity, while rheological properties are significantly
deteriorated. The mixtures with non-ionic TX-100 do not show any synergistic
effects in surface activity.
PMID- 27616062
TI - Warm-Sensitive Neurons that Control Body Temperature.
AB - Thermoregulation is one of the most vital functions of the brain, but how
temperature information is converted into homeostatic responses remains unknown.
Here, we use an unbiased approach for activity-dependent RNA sequencing to
identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that
orchestrate the homeostatic response to heat. We show that these WSNs are
molecularly defined by co-expression of the neuropeptides BDNF and PACAP. Optical
recordings in awake, behaving mice reveal that these neurons are selectively
activated by environmental warmth. Optogenetic excitation of WSNs triggers rapid
hypothermia, mediated by reciprocal changes in heat production and loss, as well
as dramatic cold-seeking behavior. Projection-specific manipulations demonstrate
that these distinct effectors are controlled by anatomically segregated pathways.
These findings reveal a molecularly defined cell type that coordinates the
diverse behavioral and autonomic responses to heat. Identification of these warm
sensitive cells provides genetic access to the core neural circuit regulating the
body temperature of mammals. PAPERCLIP.
PMID- 27616065
TI - Time of flight-secondary ion mass spectrometry analysis of protein adsorption on
a polyvinylidene difluoride surface modified by ion irradiation.
AB - We investigated the effects of nanoscopic surface modification of polyvinylidene
difluoride (PVDF) and low-density polyethylene (LDPE) by plasma-based ion
implantation on protein adsorption with time of flight-secondary ion mass
spectrometry (ToF-SIMS) analysis. The chemical composition of the LDPE and PVDF
surfaces was changed by ion irradiation. In particular, irradiation substantially
decreased the number of CH and CF bonds on the PVDF surface, but only slightly
decreased that of CH bonds for LDPE. These decreases may reflect a higher
hydrogen recombination rate of the LDPE than the PVDF surface. An increase in
oxygen was observed on both the LDPE and PVDF surfaces following ion irradiation,
but was saturated after irradiation of 1*1015cm-2 on the PVDF surface. The
hydrophilicity of the ion-irradiated LDPE surface was promoted with an increase
of the total ion fluence. Ion irradiation also changed the surface properties of
PVDF to become more hydrophilic, but the variation did not correlate with the
total ion fluence presumably due to the presence of fluorine atoms and the
saturation of oxidation. Both bovine serum albumin (BSA) and collagen adsorption
were suppressed on the LDPE surface by ion irradiation, which may have resulted
from a decrease of the hydrophobic interaction. By contrast, ion irradiation
increased protein adsorption on the PVDF surface, and BSA was adsorbed more than
collagen, whereas there was no difference in the adsorption between BSA and
collagen on the ion-irradiated LDPE surface. Moreover, the adsorption of BSA
decreased on the oxygen- and fluorine-rich PVDF surface. These results indicate
that the nanoscopic composition changes on the PVDF surface affect the adsorption
behavior of BSA. Specifically, ferroelectric property on the PVDF surface was
changed by ion irradiation and the nanoscopic change in polarity presumably
affected the protein adsorption. Our findings suggest that selective adsorption
control of protein can be achieved by ion irradiation to PVDF surface.
PMID- 27616066
TI - Quantification of the viscoelasticity of the bond of biotic and abiotic particles
adhering to solid-liquid interfaces using a window-equipped quartz crystal
microbalance with dissipation.
AB - The quartz-crystal-microbalance-with-dissipation (QCM-D) has become a powerful
tool for studying the bond viscoelasticity of biotic and abiotic colloidal
particles adhering to substratum surfaces. A window-equipped QCM-D allows high
throughput analysis of the average bond viscoelasticity, measuring over 106
particles simultaneously in one single experiment. Other techniques require
laborious analyses of individual particles. In this protocol, the quantitative
derivation of the spring-constant and drag-coefficient of the bond between
adhering colloidal particles and substratum surfaces using QCM-D is explained for
bacteria and silica particles, using the particle-mass derived for validation.
Bond viscoelasticity is calculated using a coupled resonator model, paying
special attention to the protocol for mathematical fitting needed to obtain
reliable quantitative output. Knowledge of the viscoelasticity of the bond
between colloidal particles and substratum surfaces facilitates development of
new strategies to detach adhering particles from or retain them on a surface.
PMID- 27616067
TI - Influence of membrane surface charge on adsorption of complement proteins onto
supported lipid bilayers.
AB - The complement system is an important part of the innate immune response, and
there is great interest in understanding how complement proteins interact with
lipid membrane interfaces, especially in the context of recognizing foreign
particulates (e.g., liposomal nanomedicines). Herein, a supported lipid bilayer
platform was employed in order to investigate the effect of membrane surface
charge (positive, negative, or neutral) on the adsorption of three complement
proteins. Quartz crystal microbalance-dissipation (QCM-D) experiments measured
the real-time kinetics and total uptake of protein adsorption onto supported
lipid bilayers. The results demonstrate that all three proteins exhibit
preferential, mainly irreversible adsorption onto negatively charged lipid
bilayers, yet there was also significant variation in total uptake and the
relative degree of adsorption onto negatively charged bilayers versus neutral and
positively charged bilayers. The total uptake was also observed to strongly
depend on the bulk protein concentration. Taken together, our findings contribute
to a broader understanding of the factors which influence adsorption of
complement proteins onto lipid membranes and offer guidance towards the design of
synthetic lipid bilayers with immunocompetent features.
PMID- 27616069
TI - Formulation and characterization of esterified xylo-oligosaccharides-stabilized
oil-in-water emulsions using microchannel emulsification.
AB - A series of amphiphilically esterified xylo-oligosaccharides (xylo esters) with
different fatty acids residues - decanoic acid (C-10), lauric acid (C-12) and
palmitic acid (C-16) - were enzymatically modified at 60 degrees C for 4h. These
xylo esters were used as emulsifiers to formulate oil-in-water (O/W) emulsions by
microchannel emulsification (MCE). Grooved and straight-through MCE was used to
investigate the droplet generation and/or emulsion stability. Xylo ester
stabilized oil droplets were generated smoothly from microchannels arranged
linearly or two dimensionally, while xylo ester-stabilized emulsions were less
monodispersed owing to low surface activity of the xylo esters. The combined use
of xylo esters (2.5% (w/w)) and Tween series (0.1% (w/w)) in the continuous phase
can improve the monodispersity of the resultant oil. Successful droplet
generation was achieved with the straight-through MCE using 2.5% (w/w) xylo
laurate and 0.1% (w/w) Tween 20. The optimized combination of xylo laurate and
Tween 20 inhibited coalescence and oiling off more efficiently than the droplets
solely stabilized by Tween 20 during 30days of storage.
PMID- 27616068
TI - A water-soluble and biocompatible polymeric nanolabel based on naphthalimide
grafted poly(acrylic acid) for the two-photon fluorescence imaging of living
cells and C. elegans.
AB - Polymeric nanoparticles (NPs) with two-photon (TP) activity were prepared by
grafting a naphthalimide fluorophore onto poly(acrylic acid) to yield an
amphiphilic polymer, which self-assembled in water. The NPs were characterized
using various analytical techniques such as transmission electron microscopy,
dynamic light scattering and spectroscopic measurements. The in vitro and in vivo
biocompatibilities of the NPs were assessed by a cytotoxicity assay using HeLa
cells and a feeding assay using Caenorhabditis elegans (C. elegans) as a small
animal model, respectively. Finally, TP fluorescence imaging (FI) of living cells
and C. elegans labelled with the NPs were observed by TP confocal microscopy. The
experimental outcomes demonstrated that the NPs had sufficient water-dispersity
and biocompatibility, had TP fluorescence activity, were resistant to pH
variation and illumination, and were physically stable. TP FI revealed that the
NPs could enter living cells and were primarily located in the cytoplasm. In
addition, the NPs were ingested by C. elegans during the feeding process and were
recognized and taken up by the active transport system of the intestinal cells.
These findings indicated the feasibility of using the developed NPs as a
nanolabel for TP FI. Moreover, with numerous modifiable carboxyl groups on its
surface, the NPs could act as a platform to build multifunctional probes for
potential applications in biosensing and assay labeling.
PMID- 27616071
TI - A life-threatening duodenal ulcer hemorrhage due to previously unknown primary
hyperparathyroidism.
AB - Peptic ulcer bleeding due to primary hyperparathyroidism is extremely rare. We
report a case of a 42-year-old male with life-threatening acute upper
gastrointestinal bleeding secondary to a duodenal ulcer and a history of kidney
stones. Gastroscopic therapy, Billroth II gastrointestinal anastomosis and
angiographic embolization were sequentially conducted to arrest the hemorrhage. A
complete investigative work-up revealed that the duodenal ulcer bleeding was due
to primary hyperparathyroidism coexisting with a parathyroid adenoma. Following
this event, the patient developed a severe abdominal cavity infection and sepsis.
An elective parathyroidectomy was performed, and the histology was confirmed to
be a typical parathyroid adenoma. Postoperatively, the patient's calcium and
parathyroid levels were normalized. Attention should be paid to patients with an
upper gastrointestinal ulcer, especially when it is accompanied by kidney stones.
PMID- 27616070
TI - Reoccurrence of Suspected Human-to-Turkey Transmission of H1N1 Pandemic 2009
Virus in Turkey Breeder Flocks in Ontario and Manitoba, 2016.
AB - Soon after the emergence of 2009 pandemic H1N1, the first outbreaks in breeder
turkey operations were reported that implicated human-to-turkey transmission. In
the spring of 2016, the reoccurrence of 2009 pandemic H1N1 lineage viruses
infecting breeder turkey flocks in Ontario and Manitoba, Canada, also implicated
human-to-turkey transmission. In addition to raising concerns over biosecurity
and vaccine failures, these cases once again raise the issue of whether turkeys
have the potential to act as a bridge species to generate novel influenza A virus
reassortants with public health implications.
PMID- 27616073
TI - Unravelling the Relationship between Body Mass Index and Polychlorinated Biphenyl
Concentrations Using a Mechanistic Model.
AB - Human biomonitoring (HBM) often reveals statistical associations between
persistent organic pollutant (POP) concentrations and body mass index (BMI). Both
negative and positive associations have been observed, which has been
hypothesized to reflect variable toxicokinetics in lean and obese individuals
during times of increasing and decreasing exposure. We examined this hypothesis
and assessed the influence of the obesity epidemic on time trends in human
exposure to polychlorinated biphenyls (PCB) at the population level using a
mechanistic modeling approach and data from the National Health and Nutrition
Examination Survey (NHANES) 1999-2004. Using model results for PCB-153, we
simulated cross-sectional body burden versus BMI trends (CBBTs), as well as
population level body burden versus time trends. Negative associations between
PCB-153 concentrations and BMI are predicted for all birth cohorts in HBM studies
conducted in the 1990s, while for future cross-sectional studies, we predict
negative or positive relationships depending on the age group sampled. At the
population level, demographic changes such as the obesity epidemic and population
aging had only marginal influence on the simulated rate of decline in PCB-153
concentrations between 1980 and 2010. Mechanistic bioaccumulation models can help
unravel relationships between age, BMI, and POP concentrations, informing efforts
to understand potential obesogenic effects of POPs.
PMID- 27616072
TI - Cytotoxic activities of flavonoids from a traditional Mongolian medicinal herb
Clematis aethusifolia Turcz.
AB - In the course of our search for antitumour constituents from the traditional
Mongolian medicinal herb Clematis aethusifolia Turcz., 11 flavonoids were
isolated for the first time from the dried aerial parts of the plant by flash C18
column chromatography, Sephadex LH-20 and reversed phase preparative HPLC. The
planar structures of these flavonoids were established based on 1D and 2D NMR and
high-resolution mass spectrometry. Compounds 1, 2, 4 and 5 showed moderate
cytotoxicity against a panel of five human solid tumour cell lines, including A
375, a human melanoma cell line; SK-OV-3, a human ovarian cancer cell line; A549,
a human lung cancer cell line; HCT-15, a human colorectal adenocarcinoma cell
line; and SH-SY5Y, a human neuroblastoma cell line (with IC50 values of 20-70
MUM). The obtained cytotoxic apigenin and its derivatives may be useful as
standard compounds for the quality control of the crude drug and its
preparations.
PMID- 27616074
TI - Quality by design (QbD) approach for design and development of drug-device
combination products: a case study on flunisolide nasal spray.
AB - The objective of the present study was to design and develop drug-device
combination product in particular flunisolide nasal spray (FNS) using quality by
design (QbD) approach. Quality target product profile (QTPP) of FNS was defined
and critical quality attributes (CQAs), i.e. viscosity (cp) (Y1) and D50 droplet
size distribution (DSD) (MUm) (Y2) were identified. Potential risk factors were
identified using a fish bone diagram and failure mode effect analysis (FMEA)
tools. Plackett-Burman and Box-Behnken designs were used for screening the
significant factors and optimizing the variables range, respectively. It was
observed that viscosity (cp) (Y1) was significantly impacted by formulation
variables X1: propylene glycol (PG) (%) and X2: polyethylene glycol (PEG) 3350
(%), while D50 DSD (MUm) (Y2) was significantly impacted by formulation variables
X1: PG (%), X2: PEG 3350 (%) and device variable X8: delivery volume (MUl). A
design space plot within which the CQAs remained unchanged was established at
laboratory scale. In conclusion, this study demonstrated how QbD based
development approach can be applied to the development of drug-device combination
products with enhanced understanding of the impact of formulation, process and
device variables on CQAs of drug-device combination products.
PMID- 27616075
TI - Gene panel sequencing in familial breast/ovarian cancer patients identifies
multiple novel mutations also in genes others than BRCA1/2.
AB - Breast and ovarian cancer (BC/OC) predisposition has been attributed to a number
of high- and moderate to low-penetrance susceptibility genes. With the advent of
next generation sequencing (NGS) simultaneous testing of these genes has become
feasible. In this monocentric study, we report results of panel-based screening
of 14 BC/OC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2,
ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2) in a group of 581 consecutive
individuals from a German population with BC and/or OC fulfilling diagnostic
criteria for BRCA1 and BRCA2 testing including 179 with a triple-negative tumor.
Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10
different genes, including seven different exon deletions. Of these 106
mutations, 16 (15%) were novel and only six were found in BRCA1/2. To further
characterize mutations located in or nearby splicing consensus sites we performed
RT-PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations
analyzed. In PALB2, we identified a deleterious variant in six cases. All but one
were associated with early onset BC and a positive family history indicating that
penetrance for PALB2 mutations is comparable to BRCA2. Overall, extended testing
beyond BRCA1/2 identified a deleterious mutation in further 6% of patients. As a
downside, 89 variants of uncertain significance were identified highlighting the
need for comprehensive variant databases. In conclusion, panel testing yields
more accurate information on genetic cancer risk than assessing BRCA1/2 alone and
wide-spread testing will help improve penetrance assessment of variants in these
risk genes.
PMID- 27616076
TI - Facile Formation of Redox-Active Totally Organic Nanoparticles in Water by In
Situ Reduction of Organic Precursors Stabilized through Aromatic-Aromatic
Interactions by Aromatic Polyelectrolytes.
AB - The formation of redox-active, totally organic nanoparticles in water is achieved
following a strategy similar to that used to form metal nanoparticles. It is
based on two fundamental concepts: i) complexation through aromatic-aromatic
interactions of a water-soluble precursor aromatic molecule with polyelectrolytes
bearing complementary charged aromatic rings, and ii) reduction of the precursor
molecule to achieve stabilized nanoparticles. Thus, formazan nanoparticles are
synthesized by reduction of a tetrazolium salt with ascorbic acid using
polyelectrolytes bearing benzene sulfonate residues of high linear aromatic
density, but cannot be formed in the presence of nonaromatic polyelectrolytes.
The red colored nanoparticles are efficiently encapsulated in calcium alginate
beads, showing macroscopic homogeneity. Bleaching kinetics with chlorine show
linear rates on the order of tenths of milli-meters per minute. A linear behavior
of the dependence of the rate of bleaching on the chlorine concentration is
found, showing the potential of the nanoparticles for chlorine sensing.
PMID- 27616132
TI - The epidemiology of developmental dysplasia of the hip in Japan: Findings from a
nationwide multi-center survey.
AB - BACKGROUND: It has been reported that the national incidence of developmental
dysplasia of the hip (DDH) has decreased in Japan. This is because of prevention
activities after birth since around 1970. However, cases of late-diagnosed DDH
have still been noted in some children's hospitals. There has been no recent
survey of DDH in Japan. The purpose of this study was to investigate the current
epidemiology of DDH using a comprehensive nationwide survey. METHODS: A
questionnaire was sent to orthopedic surgeons in 1987 facilities nationwide, who
were asked to complete and return a survey card on each DDH patient treated
between April 2011 and March 2013. RESULTS: A total of 783 (39%) facilities
completed and returned the card. Of these, 79% reported no cases of DDH-related
dislocation over the 2-year period, while the remaining facilities reported 1295
cases. The characteristics of children diagnosed with DDH-related dislocation
were as follows: girls (89%), left side involvement (69%), bilateral involvement
(4%), positive family history (27%), first-born (56%), and pelvic position at
birth (15%). Seasonal variation showed an increase in DDH incidence among those
born in the winter. Overall, 199 cases (15%) were diagnosed at >1 year of age,
and these included 36 cases diagnosed very late, at >3 years of age. The majority
of the 199 cases of late diagnosis had received earlier routine screening at <1
year of age. CONCLUSION: The characteristics of the children diagnosed with DDH
nationwide were similar to past data from local regions. However, many children
were diagnosed late (>1 year of age), particularly in the more populous regions.
The findings identify a need for improved early routine screening for DDH in
Japan.
PMID- 27616133
TI - Abacavir + dolutegravir + lamivudine for the treatment of HIV.
AB - INTRODUCTION: Since the last revision of both European and American guidelines
(EACS and DHHS), new data from clinical trials and cohort studies, as well as
experience in clinical practice, have prompted significant changes to the list of
recommended/preferred options for the treatment of HIV infected patients,
highlighted the role of INSTI-based regimens. Dolutegravir (DTG) in combination
with abacavir/lamivudine (ABC/3TC) is one of these preferred regimens in multiple
clinical scenarios, including treatment-naive and treatment-experienced patients.
AREAS COVERED: In this article we describe the coformulation of ABC/3TC/DTG in a
fixed-dose combination (FDC) approved in September 2014 for the treatment of HIV
infection. We focused our research on the efficacy and safety data resulting from
phase 2 and 3 clinical study, particularly on the results of both SPRING (1 and
2) and SINGLE studies. EXPERT OPINION: Triple combination therapy with
ABC/3TC/DTG should be considered among the initial options for treatment-naive
patients, being effective, well tolerated, with a high genetic barrier to
resistance along with a convenient once-daily administration. In treatment
experienced patients the single-tablet regimen (STR) based on ABC/3TC/DTG could
be used as simplification strategy in subjects with sustained viral suppression,
as the high genetic barrier of DTG should ensure a safe switch from both NNRTI or
PI based regimens.
PMID- 27616135
TI - Myocardial infarction caused by surgery: Blame inflammation not the surgeon.
PMID- 27616134
TI - Advanced glycation end-products: Mechanics of aged collagen from molecule to
tissue.
AB - Concurrent with a progressive loss of regenerative capacity, connective tissue
aging is characterized by a progressive accumulation of Advanced Glycation End
products (AGEs). Besides being part of the typical aging process, type II
diabetics are particularly affected by AGE accumulation due to abnormally high
levels of systemic glucose that increases the glycation rate of long-lived
proteins such as collagen. Although AGEs are associated with a wide range of
clinical disorders, the mechanisms by which AGEs contribute to connective tissue
disease in aging and diabetes are still poorly understood. The present study
harnesses advanced multiscale imaging techniques to characterize a widely
employed in vitro model of ribose induced collagen aging and further benchmarks
these data against experiments on native human tissues from donors of different
age. These efforts yield unprecedented insight into the mechanical changes in
collagen tissues across hierarchical scales from molecular, to fiber, to tissue
levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm)
and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues,
both using the ribose model of in vitro glycation and in native human probes.
Multiscale mechanical analysis of in vitro glycated tendons strongly suggests
that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and
fibril-fibril sliding. This study lays an important foundation for interpreting
the functional and biological effects of AGEs in collagen connective tissues, by
exploiting experimental models of AGEs crosslinking and benchmarking them for the
first time against endogenous AGEs in native tissue.
PMID- 27616136
TI - Antioxidant activity and physico-chemical parameters for the differentiation of
honey using a potentiometric electronic tongue.
AB - BACKGROUND: This work evaluates the capacity of a potentiometric electronic
tongue to differentiate between types of honey (orange blossom, rosemary, thyme,
sunflower, winter savory and honeydew honey) according to their antioxidant
level. The classical procedures used to evaluate the antioxidant potential of
honey are inappropriate for in situ monitoring on reception of batches of raw
honey in the packaging industry. They are also destructive, time-consuming and
very tedious, requiring highly expert analysts and specialised equipment.
RESULTS: The electronic tongue system made with Ag, Ni, Co, Cu and Au was able to
not only differentiate between types of honey but also to predict their total
antioxidant capacity. The discrimination ability of the system was proved by
means of a fuzzy ARTMAP type ANN, with 100% classification success. A prediction
multiple linear regression model showed that the best correlation coefficient was
for antioxidant activity (0.9666), then for electrical conductivity (0.8959) and
to a lesser extent for aw , moisture and colour. CONCLUSION: The proposed
measurement system could be a quick, easy option for the honey packaging sector
to provide continuous in-line information about a characteristic as important as
the antioxidant level. (c) 2016 Society of Chemical Industry.
PMID- 27616137
TI - A Versatile Method for Immunofluorescent Staining of Cells Cultured on Permeable
Membrane Inserts.
AB - BACKGROUND Obtaining high-quality images of cellular structures via
immunofluorescence staining is critical for cellular localization studies. Often,
these studies cannot be performed in parallel with certain oncology, virology,
pharmacokinetic, and drug absorption studies due to model system technicalities
requiring the cells to be cultured on porous membranes rather than glass or
plastic. MATERIAL AND METHODS Here, we report a method of immunofluorescent
staining of cells cultured on permeable membranes. RESULTS As proof of principle,
HeLa cells grown on Transwell(r) membrane supports were stained with
fluorescently labeled antibodies using this modified immunofluorescence staining
method and visualized by fluorescent microscopy. CONCLUSIONS This protocol is a
convenient alternative to staining cells on glass coverslips, thereby expanding
the scope and applications of this important research tool.
PMID- 27616138
TI - Higher Charlson Comorbidity Index scores do not influence Functional Independence
Measure score gains in older rehabilitation patients.
AB - AIM: To assess the effect of age-adjusted Charlson Comorbidity Index (CCI) score
on Functional Independence Measure (FIM) score gain in older rehabilitation
patients. METHODS: This prospective cohort study observed 306 older
rehabilitation patients admitted to a secondary hospital between February and
April 2015. Groups were compared using CCI score cut-offs of <=4, 5-6 and >= 7.
RESULTS: Complete FIM data were available for 280 patients. The mean age-adjusted
CCI score was 5.59 +/- 1.96. An age-adjusted CCI score <=4 correlated with higher
FIM scores at admission P = 0.015, and discharge P = 0.002, but not with a
greater gain in FIM score P = 0.067. There were no significant between-group
differences in mortality, hospital transfers or length of stay. CONCLUSION: The
Charlson age-comorbidity index was not a prognostic marker for FIM gain. Age and
comorbidity alone are not barriers to the rehabilitation of older patients.
PMID- 27616139
TI - Evolutionary robotics simulations help explain why reciprocity is rare in nature.
AB - The relative rarity of reciprocity in nature, contrary to theoretical predictions
that it should be widespread, is currently one of the major puzzles in social
evolution theory. Here we use evolutionary robotics to solve this puzzle. We show
that models based on game theory are misleading because they neglect the
mechanics of behavior. In a series of experiments with simulated robots
controlled by artificial neural networks, we find that reciprocity does not
evolve, and show that this results from a general constraint that likely also
prevents it from evolving in the wild. Reciprocity can evolve if it requires very
few mutations, as is usually assumed in evolutionary game theoretic models, but
not if, more realistically, it requires the accumulation of many adaptive
mutations.
PMID- 27616141
TI - MicroRNA-181b suppresses TAG via target IRS2 and regulating multiple genes in the
Hippo pathway.
AB - Milk fat metabolism is a complex procedure controlled by several factors. MiRNAs
(microRNAs) regulate expression of genes and influence a series of biological
procedures, such as fatty acid metabolism. Here we screened expression of goat
mammary gland's miRNA during peak-lactation and late-lactation, and found that
miR-181b expresses remarkably. Moreover, we illustrated that the over-expression
of miR-181b impaired fat metabolism while the knockdown of miR-181b promoted fat
metabolism in GMEC. These findings extend the discovery of miR-181b functioning
in mediating adipocyte differentiation, by suggesting its role in impairing fat
metabolism, which develops our cognition on the importance of miRNAs in milk fat
metabolism and synthesis. In this study, we find that over expressed miR-181b
impaired adipogenesis and inhibited miR-181b promoted adipogenesis in GMEC. Using
Luciferase reporter assay and Western Blot, IRS2 was illustrated to be a miR
181b's potential target gene. What is interesting is that miR-181b regulates
multiple key components in the Hippo pathway, such as LATS1 and YAP1 in GMECs. In
conclusion, our findings indicated that miR-181b suppress fat metabolism by means
of regulating multiple genes in the Hippo pathway and target IRS2, which promotes
further study on the function of miRNAs in milk fat metabolism and synthesis.
PMID- 27616143
TI - Periaortitis, hairy kidneys and bone lesions.
PMID- 27616142
TI - Induction of oxidative and nitrosative stresses in human retinal pigment
epithelial cells by all-trans-retinal.
AB - Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key
cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of
retinopathies such as age-related macular degeneration (AMD), however, the
underlying molecular mechanisms are far from clear. In this study, we
investigated the cytotoxicity effect and underlying molecular mechanism of atRAL
on human retinal pigment epithelium ARPE-19 cells. The results indicated that
atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses
in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up
regulation of reactive oxygen species (ROS) generation, activating mitochondrial
dependent and MAPKs signaling pathways, and finally resulting in apoptosis of
ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS
generation, indicating that NADPH oxidase activity was involved in atRAL-induced
oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was
mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM
1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above
effects could be dramatically blocked by using a nuclear factor kappa B (NF
kappaB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative
stresses were mediated by NF-kappaB. The results provide better understanding of
atRAL-induced toxicity in human RPE cells.
PMID- 27616140
TI - Layer-by-Layer Encapsulation of Probiotics for Delivery to the Microbiome.
AB - The gastrointestinal (GI) microbiome is widely investigated for its role in many
diseases. However, technologies designed for microbiome delivery are lacking.
Here, a layer-by-layer (LbL) approach is reported for probiotic encapsulation to
protect probiotics against GI tract insults and improve their adhesion and growth
on the intestines. These advantages translate to significantly enhanced survival
of LbL-probiotics in vivo.
PMID- 27616144
TI - Elevated serum levels of free interleukin-18 in adult-onset Still's disease.
AB - OBJECTIVE: IL-18 is a pro-inflammatory cytokine of the IL-1 family that is
naturally inhibited by IL-18 binding protein (IL-18BP). High levels of IL-18 have
been described in the serum of adult-onset Still's disease (AOSD) patients, but
only total IL-18 levels (including inactive IL-18 bound to IL-18BP) have been
measured. With a specific immunoassay, we aimed to measure free IL-18 serum
levels in AOSD patients and other rheumatic diseases. METHODS: An ELISA was
developed to measure free IL-18. Its sensitivity and specificity were tested by
spiking recombinant IL-18 or IL-18BP in serum and PBS supplemented with 5% BSA.
The binding affinity of IL-18 to IL-18BP was calculated by titration experiments
using the ELISA and by Biacore analysis. Sera of 37 AOSD patients and 138
controls (40 healthy controls, 30 RA, 29 SLE, 21 AS and 18 PsA) were assayed for
free IL-18, IL-18BP, total IL-18 and other cytokines. Correlations were performed
between free IL-18 and markers of disease activity in AOSD patients. RESULTS:
Free IL-18 serum levels were significantly higher in AOSD patients (median 8.89
pg/ml) than in healthy and disease controls (1.37 pg/ml; P < 0.01). Free IL-18
serum levels correlated with AOSD activity. The affinity of IL-18 to IL-18BP was
found to be much higher than previously described, with a dissociation constant
ranging from 30 to 50 pM. CONCLUSION: Free IL-18 levels are specifically elevated
in AOSD compared with other inflammatory diseases, suggesting that IL-18
represents a potential target for the treatment of AOSD.
PMID- 27616145
TI - Validity and sensitivity to change of the semi-quantitative OMERACT ultrasound
scoring system for tenosynovitis in patients with rheumatoid arthritis.
AB - OBJECTIVES: The aim was to evaluate the metric properties of the semi
quantitative OMERACT US scoring system vs a novel quantitative US scoring system
for tenosynovitis, by testing its intra- and inter-reader reliability,
sensitivity to change and comparison with clinical tenosynovitis scoring in a 6
month follow-up study. METHODS: US and clinical assessments of the tendon sheaths
of the clinically most affected hand and foot were performed at baseline, 3 and 6
months in 51 patients with RA. Tenosynovitis was assessed using the semi
quantitative scoring system (0-3) proposed by the OMERACT US group and a new
quantitative US evaluation (0-100). A sum for US grey scale (GS), colour Doppler
(CD) and pixel index (PI), respectively, was calculated for each patient. In 20
patients, intra- and inter-observer agreement was established between two
independent investigators. A binary clinical tenosynovitis score was performed,
calculating a sum score per patient. RESULTS: The intra- and inter-observer
agreements for US tenosynovitis assessments were very good at baseline and for
change for GS and CD, but less good for PI. The smallest detectable change was
0.97 for GS, 0.93 for CD and 30.1 for PI. The sensitivity to change from month 0
to 6 was high for GS and CD, and slightly higher than for clinical tenosynovitis
score and PI. CONCLUSION: This study demonstrated an excellent intra- and inter
reader agreement between two investigators for the OMERACT US scoring system for
tenosynovitis and a high ability to detect changes over time. Quantitative
assessment by PI did not add further information.
PMID- 27616146
TI - The prolactin receptor is expressed in rheumatoid arthritis and psoriatic
arthritis synovial tissue and contributes to macrophage activation.
AB - OBJECTIVES: Prolactin (PRL) is a lactation-inducing hormone with immunomodulatory
properties and is found at elevated levels in the serum of patients with RA and
other rheumatic diseases. The PRL receptor (PRLR) has been shown to be expressed
by macrophages in atherosclerotic plaques. The aim of this study was to examine
PRLR expression by synovial macrophages and its role in the regulation of
macrophage activation. METHODS: Serum monomeric 23 kDa PRL levels were measured
in 119 RA patients using a fluoroimmunometric assay. PRLR expression was assessed
in synovial tissue of 91 RA, 15 PsA and 8 OA patients by immunohistochemistry and
digital image analysis. Double IF was used to identify PRLR-expressing cells. The
effects of PRL on monocyte-derived macrophage gene expression were examined by
quantitative real-time PCR and ELISA. RESULTS: Serum PRL levels were similar in
female and male RA patients. Median (interquartile range) PRLR expression was
significantly higher (P < 0.05) in RA and PsA synovial tissue compared with OA.
PRLR colocalized with synovial CD68+ macrophages and von Willebrand factor+
endothelial cells. In vitro, PRLR was prominently expressed in IFN-gamma-and IL
10-polarized macrophages compared with other polarizing conditions. PRL by itself
had negligible effects on macrophage gene expression, but cooperated with CD40L
and TNF to increase expression of pro-inflammatory genes including IL-6, IL-8 and
IL-12beta. CONCLUSIONS: Synovial PRLR expression is enhanced in patients with
inflammatory arthritis compared with OA, and PRL cooperates with other pro
inflammatory stimuli to activate macrophages. These results identify PRL and PRLR
as potential new therapeutic targets in inflammatory arthritis.
PMID- 27616147
TI - Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole.
AB - The purpose of this study was to enhance the dissolution properties of
albendazole (ABZ) by the use of amorphous solid dispersions. Phase diagrams of
ABZ-polymer binary mixtures generated from Flory-Huggins theory were used to
assess miscibility and processability. Forced degradation studies showed that ABZ
degraded upon exposure to hydrogen peroxide and 1 N NaOH at 80 degrees C for 5
min, and the degradants were albendazole sulfoxide (ABZSX), and ABZ impurity A,
respectively. ABZ was chemically stable following exposure to 1 N HCl at 80
degrees C for one hour. Thermal degradation profiles show that ABZ, with and
without Kollidon(r) VA 64, degraded at 180 degrees C and 140 degrees C,
respectively, which indicated that ABZ could likely be processed by thermal
processing. Following hot melt extrusion, ABZ degraded up to 97.4%, while the
amorphous ABZ solid dispersion was successfully prepared by spray drying. Spray
dried ABZ formulations using various types of acids (methanesulfonic acid,
sulfuric acid and hydrochloric acid) and polymers (Kollidon(r) VA 64, Soluplus(r)
and Eudragit(r) E PO) were studied. The spray-dried ABZ with methanesulfonic acid
and Kollidon(r) VA 64 substantially improved non-sink dissolution in acidic media
as compared to bulk ABZ (8-fold), physical mixture of ABZ:Kollidon(r) VA 64 (5.6
fold) and ABZ mesylate salt (1.6-fold). No degradation was observed in the spray
dried product for up to six months and less than 5% after one-year storage. In
conclusion, amorphous ABZ solid dispersions in combination with an acid and
polymer can be prepared by spray drying to enhance dissolution and shelf
stability, whereas those made by melt extrusion are degraded.
PMID- 27616148
TI - Metastatic rectal adenocarcinoma and anal squamous cell carcinoma masquerading as
vulvar lymphangioma circumscriptum.
PMID- 27616149
TI - Reversal of congenital hypogonadotropic hypogonadism in a man with Kallmann
syndrome due to SOX10 mutation.
PMID- 27616150
TI - Entamoeba histolytica: Overexpression of the gal/galnac lectin, ehcp2 and ehcp5
genes in an in vivo model of amebiasis.
AB - The parasite Entamoeba histolytica causes intestinal amebiasis and amebic liver
abscess as its main extraintestinal manifestation. To study the in vivo events
related to inflammation and the interactions between hosts and parasites during
amebiasis, we designed a novel model of host-parasite interactions using
cellulose membrane dialysis bags containing E. histolytica trophozoites. A bag is
placed into the hamster peritoneal cavity, as has been reported in previous
studies of programmed cell death (PCD) in E. histolytica trophozoites. To
determine if virulence factors such as cysteine proteinases (EhCP2 and EhCP5) and
Gal/GalNAc lectin could be involved in the host-parasite interaction using this
model, we examined the relative expression of the ehcp2 and ehcp5 genes and the
carbohydrate recognition domain (crd) of Gal/GalNAc lectin using real-time
quantitative PCR (qRT-PCR). All analyzed genes were over-expressed 0.5h after the
initiation of the host-parasite interaction and were then progressively down
regulated. However, Gal/GalNAc lectin had the greatest increase in gene
expression 1.5h after host-parasite interaction; Gal/GalNAc lectin had a 250-fold
increase with respect to the axenically grown trophozoites, which over-express
Gal/GalNAc lectin in in vivo models. These results support the important role of
these molecules in the initiation of cell damage by E. histolytica.
PMID- 27616151
TI - Contralateral adrenal suppression on adrenocortical scintigraphy provides good
evidence showing subclinical cortisol overproduction from unilateral adenomas.
AB - Unilateral and/or predominant uptake on adrenocortical scintigraphy (ACS) may be
related to autonomous cortisol overproduction in patients with subclinical
Cushing's syndrome (SCS). However, there is no information regarding whether
increased tracer uptake on the tumor side or decreased uptake on the
contralateral side on ACS is more greatly associated with inappropriate cortisol
production. Therefore, we evaluated the relationship between quantitative 131I
6beta-iodomethyl-norcholesterol (131I-NP-59) uptake in both adrenal glands and
parameters of autonomic cortisol secretion and attempted to set a cut off for SCS
detection. The study included 90 patients with unilateral adrenal adenoma who
fulfilled strict criteria. The diagnosis of SCS was based on serum cortisol >=3.0
MUg/dL after 1-mg dexamethasone suppression test (DST) with at least 1 other
hypothalamus-pituitary-adrenal axis function abnormality. Twenty-two (27.7%)
subjects were diagnosed with SCS. The uptake rate on the affected side in the SCS
group was comparable to that in the non-functioning adenoma group. In contrast,
the uptake rate on the contralateral side was lower and the laterality ratio
significantly higher in the SCS group. The two ACS indices were correlated with
serum cortisol levels after a 1-mg DST, but uptake on the tumor side was not.
Tumor size was also important for the functional statuses of adrenal tumors and
NP-59 imaging patterns. The best cut-off point for the laterality ratio to detect
SCS was 3.07. These results clearly indicate that contralateral adrenal
suppression in ACS is good evidence showing subclinical cortisol overproduction.
PMID- 27616152
TI - Guillain-Barre syndrome in Bangladesh: validation of Brighton criteria.
AB - Guillain-Barre syndrome has a diverse clinical phenotype related to geographical
origin. To date, the majority of large-scale studies on Guillain-Barre syndrome
(GBS) have been conducted in developed countries. We aimed to evaluate the key
diagnostic features and assess the suitability of the Brighton criteria in 344
adult GBS patients from Bangladesh. All patients fulfilled the National Institute
of Neurological Diseases and Stroke (NINDS) diagnostic criteria. Standardized
data on demographic characteristics and clinical features, cerebrospinal fluid
(CSF) analysis, and nerve conduction study (NCS) results were elaborated to
measure the sensitivity of Brighton criteria. Most patients (88%) were admitted
to hospital after the nadir weakness. Symmetrical weakness and reduced reflexes
were found in 98% of patients. CSF albuminocytologic dissociation was detected in
238/269 (89%) cases and abnormal nerve physiology in 258/259 (>99%) cases. Only
27 (8%) patients received either intravenous immunoglobulin (IVIg) or
plasmapheresis. In total, 200 (58%) patients met level 1 of the Brighton
criteria; 97 (28%) patients met level 2; 42 (12%) patients met level 3; and 5
(2%) patients met level 4. This analysis showed that despite the heterogeneity of
GBS in Bangladesh, the Brighton criteria showed a high sensitivity in the
diagnosis of GBS.
PMID- 27616153
TI - Role of MDCT in the detection of early abdominal complications after orthotopic
liver transplantation.
AB - PURPOSE: This study aims to assess the role of multidetector computed tomography
(MDCT) for detecting early abdominal complications after orthotopic liver
transplantation. MATERIALS AND METHODS: We retrospectively enrolled 170 subjects
with clinical laboratory and/or echo-color Doppler abnormalities who underwent
MDCT within the first 90 days after transplantation. All images were reviewed by
two radiologists in conference and imaging results were correlated with digital
subtraction angiography, conventional cholangiography, surgery, clinical
laboratory, and/or imaging follow-up. RESULTS: No significant complication was
found in 142 patients, while vascular complications (hepatic artery thrombosis,
n=5 and stenosis, n=5; portal vein thrombosis, n=4; cava vein thrombosis, n=1;
arterial bleeding, n=1), biliary complications (anastomotic leak with biloma,
n=6), parenchymal complications (abscess, n=1; extended areas of impaired
perfusion, n=3), adrenal hemorrhage (n=1), and bowel perforation (n=1) were
identified in the remaining 28 cases. Four false-positive cases (three hepatic
artery stenoses and one hepatic artery dissection) and one false-negative case
(biloma) were diagnosed on MDCT. The sensitivity, specificity, positive
predictive value, negative predictive value, and diagnostic accuracy of MDCT in
the identification of various complications were 96%, 97%, 87%, 99%, and 97%,
respectively. CONCLUSION: MDCT is a reliable diagnostic technique in the
identification of early abdominal complications of liver recipients.
PMID- 27616154
TI - Wide-detector axial CT versus 4 cm detector helical CT for transcatheter aortic
valve replacement: iodine dose, radiation, and image quality.
AB - PURPOSE: This study aims to compare transcatheter aortic valve replacement (TAVR)
planning on 16 cm wide-detector computed tomography (CT) to TAVR planning on 4 cm
detector CT. MATERIALS AND METHODS: A total of 36 patients who had TAVR planning
axial CT on a wide-detector scanner (protocol 1) were compared to 36 patients who
had helical 4 cm detector CT (protocol 2). RESULTS: Vascular attenuation was
greater for protocol 1, but image noise, contrast-to-noise ratio, and signal-to
noise ratio were the same. Radiation dose was lower and iodine dose was less for
protocol 1. CONCLUSION: Protocol 1 had greater vascular attenuation and similar
image quality but lower radiation and less iodine compared to protocol 2.
PMID- 27616155
TI - Diagnostic and clinical utility of dynamic contrast-enhanced MR imaging in
indeterminate pulmonary nodules: a metaanalysis.
AB - OBJECTIVE: This study aims to perform a metaanalysis to assess the diagnostic
performance and clinical utility of the dynamic magnetic resonance imaging (MRI)
in discrimination of benign and malignant pulmonary nodules. MATERIALS AND
METHODS: We searched PubMed, EMBASE, and Cochrane Library from January 1995 to
May 2015 for studies evaluating the diagnostic accuracy of dynamic MRI in
discriminating benign from malignant pulmonary nodules. Methodological quality
was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2.
Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood
ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating
characteristic curve (AUC) were calculated. Potential publication bias was
investigated. RESULTS: Twelve studies with 524 malignant and 284 benign nodules
were included in this metaanalysis. The publication bias was not significant.
Summary receiver operating characteristic curve showed that AUC was 0.94 [95%
confidence interval (CI), 0.83-0.98], with pooled sensitivity of 0.95 (95% CI:
0.90, 0.97), specificity of 0.87 (95% CI: 0.72, 0.95), PLR of 7.6 (95% CI: 3.2,
18.0), NLR of 0.06 (95% CI: 0.03, 0.11), and DOR of 133 (95% CI: 45, 393),
respectively. CONCLUSION: Dynamic contrast-enhanced MRI is valuable for
discrimination of benign from malignant pulmonary nodules and is especially
useful for exclusion of malignant pulmonary nodules.
PMID- 27616156
TI - Tumour metabolism: The sugar-free, full-fat diet.
PMID- 27616158
TI - Is the time course of lexical activation and competition in spoken word
recognition affected by adult aging? An event-related potential (ERP) study.
AB - Adult aging is associated with decreased accuracy for recognizing speech,
particularly in noisy backgrounds and for high neighborhood density words, which
sound similar to many other words. In the current study, the time course of
neighborhood density effects in young and older adults was compared using event
related potentials (ERP) and behavioral responses in a lexical decision task for
spoken words and nonwords presented either in quiet or in noise. Target items
sounded similar either to many or to few other words (neighborhood density) but
were balanced for the frequency of their component sounds (phonotactic
probability). Behavioral effects of density were similar across age groups, but
the event-related potential effects of density differed as a function of age
group. For young adults, density modulated the amplitude of both the N400 and the
later P300 or late positive complex (LPC). For older adults, density modulated
only the amplitude of the P300/LPC. Thus, spreading activation to the semantics
of lexical neighbors, indexed by the N400 density effect, appears to be reduced
or delayed in adult aging. In contrast, effects of density on P300/LPC amplitude
were present in both age groups, perhaps reflecting attentional allocation to
items that resemble few words in the mental lexicon. The results constitute the
first evidence that ERP effects of neighborhood density are affected by adult
aging. The age difference may reflect either a unitary density effect that is
delayed by approximately 150ms in older adults, or multiple processes that are
differentially affected by aging.
PMID- 27616159
TI - Synthesis, characterization and in silico designing of diethyl-3-methyl-5-(6
methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene
2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents.
AB - A series of eight compounds diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl
1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxilate (KM10-17)
analogues have been prepared by conventional methods and characterized by IR,
Mass, NMR and elemental analysis. In silico docking studies on Human
topoisomerase IIbeta (PDB Id: 3QX3) have been performed for all molecules (KM10
17) synthesized. The compounds were tested for in vitro anti-proliferative
activity on VERO and 786-O cell lines. Out of all the synthesized compounds, KM11
&KM16 showed moderate activity on both cell lines. In vitro anti-microbial
activity was also checked against Bacillus subtilis (BS), Staphylococcus aurous
(SA), Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Candida albicans
(CA) by well diffusion method. The compound KM11 was found to have highest zone
of inhibition against BS, SA, PA and EC. The molecules KM13 and KM16 exhibited
good activity against CA. The compounds KM14 and KM16 indicated good zone of
inhibition against BS.
PMID- 27616160
TI - Fast-Dissolving, Prolonged Release, and Antibacterial Cyclodextrin/Limonene
Inclusion Complex Nanofibrous Webs via Polymer-Free Electrospinning.
AB - We have proposed a new strategy for preparing free-standing nanofibrous webs from
an inclusion complex (IC) of a well-known flavor/fragrance compound (limonene)
with three modified cyclodextrins (HPbetaCD, MbetaCD, and HPgammaCD) via
electrospinning (CD/limonene-IC-NFs) without using a polymeric matrix. The
experimental and computational modeling studies proved that the stoichiometry of
the complexes was 1:1 for CD/limonene systems. MbetaCD/limonene-IC-NF released
much more limonene at 37, 50, and 75 degrees C than HPbetaCD/limonene-IC-NF and
HPgammaCD/limonene-IC-NF because of the greater amount of preserved limonene.
Moreover, MbetaCD/limonene-IC-NF has released only 25% (w/w) of its limonene,
whereas HPbetaCD/limonene-IC-NF and HPgammaCD/limonene-IC-NF released 51 and 88%
(w/w) of their limonene in 100 days, respectively. CD/limonene-IC-NFs exhibited
high antibacterial activity against E. coli and S. aureus. The water solubility
of limonene increased significantly and CD/limonene-IC-NFs were dissolved in
water in a few seconds. In brief, CD/limonene-IC-NFs with fast-dissolving
character enhanced the thermal stability and prolonged the shelf life along with
antibacterial properties could be quite applicable in food and oral care
applications.
PMID- 27616157
TI - Understanding the regulation of vertebrate hematopoiesis and blood disorders -
big lessons from a small fish.
AB - Hematopoietic stem cells (HSCs) give rise to all differentiated blood cells.
Understanding the mechanisms that regulate self-renewal and lineage specification
of HSCs is key for developing treatments for many human diseases. Zebrafish have
emerged as an excellent model for studying vertebrate hematopoiesis. This review
will highlight the unique strengths of zebrafish and important findings that have
emerged from studies of blood development and disorders using this system. We
discuss recent advances in our understanding of hematopoiesis, including the
origin of HSCs, molecular control of their development, and key signaling
pathways involved in their regulation. We highlight significant findings from
zebrafish models of blood disorders and discuss their application for
investigating stem cell dysfunction in disease and for the development of new
therapeutics.
PMID- 27616161
TI - Osteogenic differentiation of preosteoblasts on a hemostatic gelatin sponge.
AB - Bone tissue engineering provides many advantages for repairing skeletal defects.
Although many different kinds of biomaterials have been used for bone tissue
engineering, safety issues must be considered when using them in a clinical
setting. In this study, we examined the effects of using a common clinical item,
a hemostatic gelatin sponge, as a scaffold for bone tissue engineering. The use
of such a clinically acceptable item may hasten the translational lag from
laboratory to clinical studies. We performed both degradation and
biocompatibility studies on the hemostatic gelatin sponge, and cultured
preosteoblasts within the sponge scaffold to demonstrate its osteogenic
differentiation potential. In degradation assays, the gelatin sponge demonstrated
good stability after being immersed in PBS for 8 weeks (losing only about 10% of
its net weight and about 54% decrease of mechanical strength), but pepsin and
collagenases readily biodegraded it. The gelatin sponge demonstrated good
biocompatibility to preosteoblasts as demonstrated by MTT assay, confocal
microscopy, and scanning electron microscopy. Furthermore, osteogenic
differentiation and the migration of preosteoblasts, elevated alkaline
phosphatase activity, and in vitro mineralization were observed within the
scaffold structure. Each of these results indicates that the hemostatic gelatin
sponge is a suitable scaffold for bone tissue engineering.
PMID- 27616162
TI - Resistance training improves inflammatory level, lipid and glycemic profiles in
obese older women: A randomized controlled trial.
AB - The main purpose of the present study was to investigate the effect of resistance
training on inflammatory levels, lipid and glycemic profile in obese older women.
Thirty-eight obese older women (68.2+/-4.2years, and 41.0+/-6.2% of body fat)
were randomly assigned to one of two groups: A training group (TG, n=19) that
performed 8weeks of RT; or a control group (CG, n=19) that did not perform any
type of exercise. The RT program consisted of 8 whole-body exercises for 3 sets
of 10-15 repetition maximum (RM) carried out 3 times a week. Anthropometric, body
composition (DXA), muscular strength (1RM), and blood sample measurements were
performed pre- and post-training. After the intervention period, the TG
demonstrated significantly (P<0.05) lower values than CG for interleukin-6
(TG=3.3+/-1.2pg/mL vs. CG=3.8+/-1.4pg/mL), tumor necrosis factor alpha (TG=3.1+/
1.5pg/mL vs. CG=3.5+/-1.8pg/mL), C-reactive protein (TG=1.8+/-1.4mg/L vs.
CG=3.2+/-1.8mg/L), low-density lipoprotein (TG=85.1+/-11.0mg/dL vs. CG=148.7+/
0.1mg/dL), glucose (TG=90.8+/-11.1mg/dL vs. CG=97.9+/-6.9mg/dL), trunk fat
(TG=12.7+/-3.5kg vs. CG=14.1+/-4.3kg), and total body fat (TG=37.5+/-5.7% vs.
CG=43.1+/-5.6%). Furthermore, TG presented significantly (P<0.05) higher values
for high-density lipoprotein (TG=58.3+/-15.4mg/dL vs. CG=55.2+/-11.8mg/dL). These
results suggest that 8weeks of RT promote improvements on inflammatory levels,
and the lipid and glycemic profile in obese older women. These findings further
support the important role of RT in healthy aging.
PMID- 27616163
TI - Muscle strength, postural balance, and cognition are associated with braking time
during driving in older adults.
AB - BACKGROUND: Despite the well-known declines in driving performance with advancing
age, there is little understanding of the specific factors that predict changes
in key determinants such as braking time. OBJECTIVES: The aims of this study were
to determine the extent to which age, muscle strength, cognition and postural
balance are associated with braking performance in middle-aged and older adults.
METHODS: Male and female middle-aged adults (n=62, age=39.3+/-7.1years) and older
adults (n=102, age=70.4+/-5.8years) were evaluated for braking performance, as
well as in several motor and cognitive performance tasks. The motor evaluation
included isokinetic ankle plantar flexor muscle strength, handgrip strength, and
postural balance with and without a cognitive task. The cognitive assessment
included the Mini Mental State Examination. Braking performance was measured
using a driving simulator. RESULTS: Older adults exhibited 17% slower braking
time, lower strength, and poorer performance in the postural balance (p<0.001).
For both older and middle-aged adults, significant correlates of braking time
included performance in the postural balance tests, muscle strength, and
cognitive function. However, after full model adjustment, only postural balance
and cognitive function were significantly associated. CONCLUSION: Muscle
strength, postural balance, and cognition are associated with braking time, and
may affect the safety of and driving performance in older adults. These findings
may help to inform specific targeted interventions that could preserve driving
performance during aging.
PMID- 27616164
TI - Long term bone alterations in aged rats suffering type 1 diabetes.
AB - : Increasing duration of type 1 diabetes mellitus alters bone metabolism.
Clinical studies and experimental studies in long bones of rats with
experimentally induced diabetes have reported a decrease in bone density. Few
studies have explored this diabetes related alteration in the maxillae. Given
that this finding could indicate the possible development of osteopenia in the
maxilla in the long term, the present study sought to analyze alterations in
alveolar bone in aged rats, 12, 18, and 24weeks after inducing diabetes, and
compare alveolar bone response to that of tibial subchondral bone at the same
experimental times. Thirty-six male Wistar rats, 130g body weight, were divided
into 2 groups: an experimental group (E) receiving a single i.p. 60mg/kg dose of
streptozotocin, and a control group (C). Both the control and experimental groups
were divided into 3 sub-sets, according to the time of euthanasia: 12, 18 and
24weeks. The alveolar bone and tibiae were examined histologically and
histomorphometrically. The results were analyzed using Student's t-test; a value
of p<0.05 was considered statistically significant. RESULTS: Subchondral bone
volume and bone activity/remodeling, mainly bone rest, were significantly lower
in diabetic animals compared to controls, at both 12 and 18weeks. No differences
in alveolar bone parameters were observed between diabetic and control animals at
either of the experimental times. Animals surviving at 24weeks showed few
trabeculae at rest and severe destruction of dental and periodontal tissues. The
results of the present study show that diabetic osteopenia is evident in the
tibia at 12 and at 18weeks, whereas its effects on the maxilla can be seen at
24weeks, with substantial destruction of alveolar bone and of the remaining
periodontal and dental tissues. All the above observations highlight the need for
preventive oral care in diabetic patients, before irreversible damage to dental
and periodontal tissues occurs.
PMID- 27616165
TI - Fucoidan-Mimetic Glycopolymers as Tools for Studying Molecular and Cellular
Responses in Human Blood Platelets.
AB - The marine sulfated polysaccharide fucoidan displays superior ability to induce
platelet aggregation compared to other sulfated polysaccharides. As such, it is
an attractive tool for studying molecular and cellular responses in activated
platelets. The heterogeneous structure, however, poses a problem in such
applications. This study describes the synthesis of sulfated alpha-l-fucoside
pendant poly(methacryl amides) with homogeneous structures. By using both thiol
mediated chain transfer and reversible addition-fragmentation chain transfer
polymerization techniques, glycopolymers with different chain lengths are
obtained. These glycopolymers show platelet aggregation response and surface
changes similar to those of fucoidan, and cause platelet activation through
intracellular signaling as shown by extensive protein tyrosine phosphorylation.
As the platelet activating properties of the glycopolymers strongly mimic those
of fucoidan, this study concludes these fucoidan-mimetic glycopolymers are unique
tools for studying molecular and cellular responses in human blood platelets.
PMID- 27616166
TI - Integrative approach revises the frequently misidentified species of Sardinella
(Clupeidae) of the Indo-West Pacific Ocean.
AB - To deal with the difficulties of species differentiation and delimitation among
the commercially important sardines from the genus Sardinella, an integrative
approach was adopted, incorporating traditional taxonomy with four DNA markers
(coI, cytb, 16s and nuclear rag2). Combining these methodologies has enabled a
thorough re-description of three of the most common species of Sardinella of the
Indo-west Pacific Ocean: white sardinella Sardinella albella, fringescale
sardinella Sardinella fimbriata and the goldstripe sardinella Sardinella gibbosa,
as well as a description of a new species, Gon's sardinella Sardinella goni, from
the island of Boracay, Philippines. In addition, extensive widespread sampling of
S. gibbosa reveals a significant genetic separation between the populations from
the western Indian Ocean and the west Pacific Ocean, despite no supporting
morphological differentiation. An updated morphological key of the species of
Sardinella of the Indo-west Pacific Ocean is also provided in order to minimize
future misidentifications within these economically important taxa. Finally, the
genetic and morphological variabilities within and between the investigated
species are used to discuss their biogeographical distribution and possible
processes of speciation.
PMID- 27616167
TI - 2015 Information Processing in Cells and Tissues (IPCAT 2015).
PMID- 27616168
TI - OCCUPATIONAL ALLERGY.
PMID- 27616169
TI - SKIN CARE FOR ATOPIC DERMATITIS CHILDREN IN GROUP LIFE.
PMID- 27616170
TI - CLINICAL POINTS IN USING ANTIHISTAMINE FOR THE PATIENTS WITH ALLERGIC RHINITIS
BASED ON PG-MARJ 2016.
PMID- 27616171
TI - REGENERATIVE MEDICINE.
PMID- 27616172
TI - EPIDEMIOLOGY AND CLINICAL FEATURE OF ALLERGIC RHINITIS IN CHILDREN.
PMID- 27616173
TI - STRATEGIES OF THE TREATMENT TO REFRACTORY ALLERGIC CONJUNCTIVAL DISORDERS.
PMID- 27616174
TI - THE DISPERSION OF HERBACEOUS PLANT POLLEN IN ITO CITY, SHIZUOKA.
AB - BACKGROUND: Airborne pollen was examined in Ito City, Shizuoka for the purpose of
treatment and prophylaxis pollen allergies because the patients with pollen
allergy to herbaceous plants have recently increased. METHODS: Setting up a
Durham's sampler, we measured airborne pollen identified and classified: Poaceae,
Polygonaceae, Amaranthaceae, Urticaceae, Cannabaceae, Ambrosia and Artemisia
indica.We studied whether each airborne pollen count has something to do with
weather condition (2004-2015). RESULTS: Average total airborne Poaceae pollen
count and standard deviation from January to June was 19.4+/-5.5 cells/cm(2),
average total airborne Polygonaceae pollen count and standard deviation from
April to September was 11.6+/-13.4 cells/cm(2). Airborne Poaceae, Amaranthaceae,
Cannabaceae, Uriticaceae. Ambrosia and Artamisia indica pollen count from July to
Deccember in order: 34.0+/-15.5 cells/cm(2), 1.3+/-1.1 cells/cm(2), 8.7+/
6.4cells/cm(2), 4.9+/-6.4 cells/cm(2), 10.5+/-7.8 cells/cm(2), and 13.6+/-16.3
cells/cm(2).Cannabaceae admitted that its airborne pollen count has negative
correlation to the rainfall.Artemisia indica admitted that its airborne pollen
count has negative correlation to the average temperature. CONCLUSION: Herbaceous
plants pollen doesn't cause allergies because it is much less than tree pollen in
ItoCity.It is thought that the diversity of the plants keep the people from
having a serious allergy to pollen with awarm weather in this area.
PMID- 27616176
TI - INCIDENCE OF APNEA ATTACK AS ALLERGIC REACTION AFTER ORAL FOOD CHALLENGE IN
PATIENT WITH IgE-MEDIATED WHEAT ALLERGY.
AB - Anaphylaxis is a severe allergic reaction that is rapid in onset and might cause
death. Although wheezes, dyspnea or loss of consciousness are known to occur with
severe allergic reactions with IgE-mediated food allergy, reports of apnea attack
associated with IgE-mediated food allergy are rare. In this case, 9-year-old boy
with IgE-mediated wheat allergy experienced apnea attack with strong desaturation
after an immediate allergic reaction including erythema, abdominal pain,
vomiting, and anaphylactic shock. The patient had asphyxia and cyanosis confirmed
by medical staff when his oxygen saturation decreased to the 60% level, and he
had occasional asphyxia over 10 seconds with no thoracic motion after a
desaturation episode. Central apnea attack might be occurred in patient with IgE
mediated food allergy. However, the exact mechanism responsible remains unknown
and further research is needed.
PMID- 27616175
TI - THE COMPARISON OF EFFECTIVENESS OF SLOW SPECIFIC ORAL IMMUNOTHERAPY FOR WHEAT
ALLERGY USING TWO DIFFERENT INTAKE FREQUENCY.
AB - OBJECTIVE: We performed a constructive study on the effectiveness of oral
immunotherapy for wheat allergy using two different intake frequency, and
evaluated the impact of intake frequency. SUBJECTS: Of all the subjects who had a
positive result in an oral food challenge test for udon (wheat noodles), informed
consent was obtained from 49 subjects. Forty-one of the subjects successfully
completed testing; data was tabulated for only the 16 in each group who complied
with their assigned intake frequency. METHOD: Oral immunotherapy was administered
after randomly dividing the subjects into the following two groups according to
intake frequency: the frequent group, whose intake was six times/week or more;
and the intermittent group, whose intake was two times/week. The ability of these
patients to ingest the noodles at the target dose was evaluated after 6 months.
RESULTS: After six months, the proportion of subjects who had a negative result
on testing with the target dose (20g dried noodle weight for subjects <=3 years
of age, and 50g dried noodle weight for those >=4 years of age) or who were
capable of the target intake within six months was 75%, and there was no
difference among the both groups. CONCLUSION: The findings suggest that even when
intake frequency is reduced to twice/week, no clear difference is seen with the
target dose after six months of immunotherapy.
PMID- 27616177
TI - [Not Available].
PMID- 27616178
TI - [Not Available].
PMID- 27616179
TI - [Not Available].
PMID- 27616180
TI - It is time to address ambulatory central venous line infections in pediatric
hematology/oncology patients.
PMID- 27616181
TI - Elastic instabilities in planar elongational flow of monodisperse polymer
solutions.
AB - We investigate purely elastic flow instabilities in the almost ideal planar
stagnation point elongational flow field generated by a microfluidic optimized
shape cross-slot extensional rheometer (OSCER). We use time-resolved flow
velocimetry and full-field birefringence microscopy to study the behavior of a
series of well-characterized viscoelastic polymer solutions under conditions of
low fluid inertia and over a wide range of imposed deformation rates. At low
deformation rates the flow is steady and symmetric and appears Newtonian-like,
while at high deformation rates we observe the onset of a flow asymmetry
resembling the purely elastic instabilities reported in standard-shaped cross
slot devices. However, for intermediate rates, we observe a new type of elastic
instability characterized by a lateral displacement and time-dependent motion of
the stagnation point. At the onset of this new instability, we evaluate a well
known dimensionless criterion M that predicts the onset of elastic instabilities
based on geometric and rheological scaling parameters. The criterion yields
maximum values of M which compare well with critical values of M for the onset of
elastic instabilities in viscometric torsional flows. We conclude that the same
mechanism of tension acting along curved streamlines governs the onset of elastic
instabilities in both extensional (irrotational) and torsional (rotational)
viscoelastic flows.
PMID- 27616182
TI - Sea buckthorn as a source of important bioactive compounds in cardiovascular
diseases.
AB - Hippophae rhamnoides (sea buckthorn) offers many health benefits. It has
significant cardioprotective activity and exerts many positive healing effects on
the cardiovascular system, including inhibiting blood platelet activation
(especially platelet aggregation), lowering cholesterol concentration and blood
pressure, and providing antioxidant activity. In addition, sea buckthorn has
antibacterial and antiviral properties. The leaves and fruits of the plant, and
its oils, are sources of many bioactive substances including vitamins (A, C and
E), unsaturated fatty acids, phenolic compounds, especially flavonoids, and
phytosterols, which bestow positive effects on the cardiovascular system. This
review article summarizes the current knowledge of the biological roles of sea
buckthorn in cardiovascular diseases.
PMID- 27616183
TI - Pressurized brines in continental Antarctica as a possible analogue of Mars.
AB - Interest in brines in extreme and cold environments has recently increased after
they have been found on Mars. Those brines can be potential new subsurface
habitats for peculiar ecosystems. In the McMurdo Dry Valleys of the Antarctic,
the best analogue for Mars conditions, only a few cases of brines have been
identified in some perennially frozen lakes and in one case in an underground
aquifer. Here, we present the occurrence of pressurized brines in a shallow
perennially ice-covered lake south of 70 degrees S in an ice-free area of
Victoria Land, Antarctica. For the first time, we also imaged, by means of ground
penetrating radar data, the existence of a pingo-like-feature (PLF) formed by the
extrusion of brines, which has also been confirmed by borehole evidence. Those
brines are fed by an underground talik external to the lake basin, enhancing the
possibility of unexploited ecosystems that could find an analogue in Martian
environments.
PMID- 27616184
TI - Grazing improves C and N cycling in the Northern Great Plains: a meta-analysis.
AB - Grazing potentially alters grassland ecosystem carbon (C) and nitrogen (N)
storage and cycles, however, the overall direction and magnitude of such
alterations are poorly understood on the Northern Great Plains (NGP). By
synthesizing data from multiple studies on grazed NGP ecosystems, we quantified
the response of 30 variables to C and N pools and fluxes to grazing using a
comprehensive meta-analysis method. Results showed that grazing enhanced soil C
(5.2 +/- 4.6% relative) and N (11.3 +/- 9.1%) pools in the top layer, stimulated
litter decomposition (26.8 +/- 18.4%) and soil N mineralization (22.3 +/- 18.4%)
and enhanced soil NH4(+) (51.5 +/- 42.9%) and NO3(-) (47.5 +/- 20.7%)
concentrations. Our results indicate that the NGP grasslands have sequestered C
and N in the past 70 to 80 years, recovering C and N lost during a period of
widespread grassland deterioration that occurred in the first half of the 20(th)
century. Sustainable grazing management employed after this deterioration has
acted as a critical factor for C and N amelioration of degraded NGP grasslands
and about 5.84 Mg C ha(-1) CO2-equivalent of anthropogenic CO2 emissions has been
offset by these grassland soils.
PMID- 27616186
TI - Decline in alcohol use among adolescents in Slovakia: a reason for optimism?
AB - OBJECTIVES: To analyze selected indicators of alcohol use (lifetime use,
initiation of drinking at <=13 years of age, weekly use, beverage preferences,
initiation of drunkenness at <=13 years of age and lifetime drunkenness) in
adolescents in Slovakia from 2006 to 2014. STUDY DESIGN: The Health Behaviour in
School Aged Children (HBSC) study is a cross-sectional questionnaire study.
METHODS: A standardized uniform questionnaire was used in representative samples
of 11-, 13- and 15-year-old adolescents. In Slovakia, the HBSC study was
undertaken in 2006 (n = 3972), 2010 (n = 5089) and 2014 (n = 4369). RESULTS: Over
the study period, decreases were observed in weekly drinking (from 34.3% to 21.0%
in 15-year-old boys and from 22.1% to 11.9% in 15-year-old girls), lifetime
drinking and initiation of drinking at <=13 years of age. In terms of beverage
preferences, the reduction in beer consumption was most notable. Approximately
one-third of respondents got drunk for the first time at <=13 years of age, and
this remained consistent throughout the study period. CONCLUSIONS: The declining
trend in alcohol use among adolescents in Slovakia may reflect a progressive
change in the social environment and is attributable, at least in part, to policy
improvements such as pricing and stricter legislation and enforcement.
PMID- 27616187
TI - Osteoarthritis: from pathogenic mechanisms and recent clinical developments to
novel prospective therapeutic options.
AB - Osteoarthritis (OA) is a degenerative joint disease that, despite recent
progress, has no curative treatment. Considerable research has recently been
initiated to identify new potential therapeutic targets. In this review, we will
set forth some of the major discoveries in the past 5 years, notably those
dealing with the identification of pathogenic factors [hypoxia-inducible factors
(HIFs), complement, transforming growth factor (TGF)-beta and zinc-ZIP8]. New
drugs and concepts currently in clinical development [anti-nerve growth factor
(NGF), mesenchymal stromal cells and fibroblast growth factor (FGF)-18] will then
be addressed. Finally, we will consider prospective avenues that could lead to
mid-to-long-term developments of novel therapeutic concepts, notably those
dealing with autophagy regulation and induced pluripotent stem cells.
PMID- 27616185
TI - Molecular evolutionary dynamics of cytochrome P450 monooxygenases across
kingdoms: Special focus on mycobacterial P450s.
AB - Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s),
great progress has been made in understanding their structure-function
relationship, diversity and application in producing compounds beneficial to
humans. However, the molecular evolution of P450s in terms of their dynamics both
at protein and DNA levels and functional conservation across kingdoms still needs
investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450
families (bacteria -42; fungi -19; plant -28; animal -22; plant and animal -1 and
common P450 family -1) and found highly conserved and rapidly evolving P450
families. Results suggested that bacterial P450s, particularly P450s belonging to
mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria
possess the highest P450 diversity percentage compared to other microbes and have
a high coverage of P450s (>=1%) in their genomes, as found in fungi and plants.
Phylogenetic and functional analyses revealed the functional conservation of
P450s despite belonging to different biological kingdoms, suggesting the
adherence of P450s to their innate function such as their involvement in either
generation or oxidation of steroids and structurally related molecules, fatty
acids and terpenoids. This study's results offer new understanding of the dynamic
structural nature of P450s.
PMID- 27616189
TI - Fast-track cardiac care for adult cardiac surgical patients.
AB - BACKGROUND: Fast-track cardiac care is a complex intervention involving several
components of care during cardiac anaesthesia and in the postoperative period,
with the ultimate aim of early extubation after surgery, to reduce length of stay
in the intensive care unit and in the hospital. Safe and effective fast-track
cardiac care may reduce hospital costs. This is an update of a Cochrane review
first published in 2003, updated in 2012 and updated now in 2016. OBJECTIVES: To
determine the safety and effectiveness of fast-track cardiac care compared with
conventional (not fast-track) care in adult patients undergoing cardiac surgery.
Fast-track cardiac care intervention includes administration of low-dose opioid
based general anaesthesia or use of a time-directed extubation protocol, or both.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
(CENTRAL; 2015, Issue 5), MEDLINE (January 2012 to May 2015), Embase (January
2012 to May 2015), the Cumulative Index to Nursing and Allied Health Literature
(CINAHL; January 2012 to May 2015) and the Institute for Scientific Information
(ISI) Web of Science (January 2012 to May 2015), along with reference lists of
articles, to identify additional trials. We applied no language restrictions.
SELECTION CRITERIA: We included all randomized controlled trials of adult cardiac
surgical patients (coronary artery bypass grafts, aortic valve replacement,
mitral valve replacement) that compared fast-track cardiac care and conventional
(not fast-track) care groups. We focused on the following fast-track
interventions, which were designed for early extubation after surgery:
administration of low-dose opioid-based general anaesthesia during cardiac
surgery and use of a time-directed extubation protocol after surgery. The primary
outcome was risk of mortality. Secondary outcomes included postoperative
complications, reintubation within 24 hours of surgery, time to extubation,
length of stay in the intensive care unit and in the hospital, quality of life
after surgery and hospital costs. DATA COLLECTION AND ANALYSIS: Two review
authors independently assessed trial quality and extracted study data. We
contacted study authors for additional information. We calculated a Peto odds
ratio (OR) for risk of mortality and used a random-effects model to report risk
ratio (RR), mean difference (MD) and 95% confidence intervals (95% CIs) for all
secondary outcomes. MAIN RESULTS: We included 28 trials (4438 participants) in
the updated review. We considered most participants to be at low to moderate risk
of death after surgery. We assessed two studies as having low risk of bias and 11
studies high risk of bias. Investigators reported no differences in risk of
mortality within the first year after surgery between low-dose versus high-dose
opioid-based general anaesthesia groups (OR 0.53, 95% CI 0.25 to 1.12; eight
trials, 1994 participants, low level of evidence) and between a time-directed
extubation protocol versus usual care (OR 0.80, 95% CI 0.45 to 1.45; 10 trials,
1802 participants, low level of evidence).Researchers noted no significant
differences between low-dose and high-dose opioid-based anaesthesia groups in the
following postoperative complications: myocardial infarction (RR 0.98, 95% CI
0.48 to 1.99; eight trials, 1683 participants, low level of evidence), stroke (RR
1.17, 95% CI 0.36 to 3.78; five trials, 562 participants, low level of evidence)
and tracheal reintubation (RR 1.77, 95% CI 0.38 to 8.27; five trials, 594
participants, low level of evidence).Comparisons with usual care revealed no
significant differences in the risk of postoperative complications associated
with a time-directed extubation protocol: myocardial infarction (RR 0.59, 95% CI
0.27 to 1.31; eight trials, 1378 participants, low level of evidence), stroke (RR
0.85, 95% CI 0.33 to 2.16; 11 trials, 1646 participants, low level of evidence)
and tracheal reintubation (RR 1.34, 95% CI 0.74 to 2.41; 12 trials, 1261
participants, low level of evidence).Although levels of heterogeneity were high,
low-dose opioid anaesthesia was associated with reduced time to extubation
(reduction of 4.3 to 10.5 hours, 14 trials, 2486 participants, low level of
evidence) and length of stay in the intensive care unit (reduction of 0.4 to 7.0
hours, 12 trials, 1394 participants, low level of evidence). Use of a time
directed extubation protocol was associated with reduced time to extubation
(reduction of 3.7 to 8.8 hours, 16 trials, 2024 participants, low level of
evidence) and length of stay in the intensive care unit (reduction of 3.9 to 10.5
hours, 13 trials, 1888 participants, low level of evidence). However, these two
fast-track care interventions were not associated with reduced total length of
stay in the hospital (low level of evidence). AUTHORS' CONCLUSIONS: Low-dose
opioid-based general anaesthesia and time-directed extubation protocols for fast
track interventions have risks of mortality and major postoperative complications
similar to those of conventional (not fast-track) care, and therefore appear to
be safe for use in patients considered to be at low to moderate risk. These fast
track interventions reduced time to extubation and shortened length of stay in
the intensive care unit but did not reduce length of stay in the hospital.
PMID- 27616190
TI - Highly Hydrophobic and Superoleophilic Nanofibrous Mats with Controllable Pore
Sizes for Efficient Oil/Water Separation.
AB - Both the wettability and pore size of filtration materials are of great
importance in oil/water separation. However, conventional strategies have mainly
focused on the fabrication of filtration materials with special wettability,
regardless of the pore size. Herein, we demonstrated the design and construction
of special wettable nanofibrous mats with tunable pore sizes as filtration
materials for selective and efficient separation of oil from oil/water mixtures.
The nanofibrous mats with different pore sizes were prepared by the
electrospinning approach using a stainless steel wire mesh as the collector, and
the results indicated that the pore size of the nanofibrous mats gradually
increased with the decrease in the mesh number. The results of the wettability
behavior demonstrated that all of the nanofibrous mats showed highly hydrophobic
and superoleophilic properties. Owing to the special wettability and the porous
structure, the nanofibrous mats were sequentially applied for oil/water
separation, and they showed excellent ability to separate both layered oil/water
mixture and water-in-oil emulsion; moreover, it was also found that the oil flux
could be highly improved by controlling the pore size of the nanofibrous mat and
that the oil flux of the nanofibrous mat with the largest pore size was about 10
times higher than that of the conventional nonwoven mat that had the smallest
pore size. The nanofibrous mats developed with controllable pore sizes can
therefore be practically used as highly efficient filtration materials in the
management of oily water.
PMID- 27616191
TI - A High Contrast Tri-state Fluorescent Switch: Properties and Applications.
AB - A high contrast tri-state fluorescent switch (FSPTPE) with both emission color
change and on/off switching is achieved in a single molecular system by fusing
the aggregation-induced emissive tetraphenylethene (TPE) with a molecular switch
of spiropyran (SP). In contrast to most of the reported solid-state fluorescent
switches, FSPTPE only exists in the amorphous phase in the ring-closed form owing
to its highly asymmetric molecular geometry and weak intermolecular interactions,
which leads to its grinding-inert stable cyan emission in the solid state. Such
an amorphous phase facilitates the fast response of FSPTPE to acidic gases and
induces the structural transition from the ring-closed form to ring-open form,
accompanied with the "Off" state of the fluorescence. The structural transition
leads to a planar molecular conformation and high dipole moment, which further
results in strong intermolecular interactions and good crystallinity, so when the
acid is added together with a solvent, both the ring-opening reaction and re
crystallization can be triggered to result in an orange emissive state. The
reversible control between any two of the three states (cyan/orange/dark) can be
achieved with acid/base or mechanical force/solvent treatment. Because of the
stable initial state and high color contrast (Deltalambda=120 nm for cyan/orange
switch, dark state PhiF <0.01 %), the fluorescent switch is very promising for
applications such as displays, chemical or mechanical sensing, and anti
counterfeiting.
PMID- 27616188
TI - Probing the causal role of prestimulus interregional synchrony for perceptual
integration via tACS.
AB - The phase of prestimulus oscillations at 7-10 Hz has been shown to modulate
perception of briefly presented visual stimuli. Specifically, a recent combined
EEG-fMRI study suggested that a prestimulus oscillation at around 7 Hz represents
open and closed windows for perceptual integration by modulating connectivity
between lower order occipital and higher order parietal brain regions. We here
utilized brief event-related transcranial alternating current stimulation (tACS)
to specifically modulate this prestimulus 7 Hz oscillation, and the synchrony
between parietal and occipital brain regions. To this end we tested for a causal
role of this particular prestimulus oscillation for perceptual integration. The
EEG was acquired at the same time allowing us to investigate frequency specific
after effects phase-locked to stimulation offset. On a behavioural level our
results suggest that tACS did modulate perceptual integration, however, in an
unexpected manner. On an electrophysiological level our results suggest that
brief tACS does induce oscillatory entrainment, as visible in frequency specific
activity phase-locked to stimulation offset. Together, our results do not
strongly support a causal role of prestimulus 7 Hz oscillations for perceptual
integration. However, our results suggest that brief tACS is capable of
modulating oscillatory activity in a temporally sensitive manner.
PMID- 27616192
TI - A randomized clinical trial on the comparison between hair shaving and snipping
prior to laser hair removal sessions in women suffering from hirsutism.
AB - BACKGROUND AND OBJECTIVES: Hirsutism or excess hair growth is a common
dermatological problem in females, affecting up to 10% of females worldwide. We
aimed this study to compare the two hair-shortening methods shaving vs. snipping
among hirsute women regarding the outcome of the therapy and also the paradoxical
hypertrichosis phenomenon (terminal hair regrowth) 6 months after the final
therapy session. MATERIALS AND METHODS: In this study, 129 premenopausal women
affected by hirsutism were randomly divided into two study groups according to
hair-shortening method: shaving as group A (66 patients) and hair shortening by
scissor as group B (63 patients). Each patient received six alexandrite laser
therapy sessions every month for six consecutive months. Chin hairs in a 5 * 5
cm2 zone were counted, and the paradoxical hair regrowth was evaluated four times
during the study: once at baseline, once before the third session, once before
the sixth session, and once 6 months after the last laser session. RESULTS:
Before the third session, the counts were 15.06 +/- 5.20 in group A and 13.07 +/-
4.44 in group B (P = 0.022); both counts were meaningfully less than the baseline
count (P < 0.001). The counts before the sixth session were 2.80 +/- 1.16 in
group A and 2.71 +/- 1.12 in group B (P = 0.673); the counts were significantly
lower than the previous session (P < 0.001). Six months after the last laser
session, the counts were 11.27 +/- 9.30 in group A and 8.15 +/- 3.12 in group B
(P = 0.012). Paradoxical hypertrichosis was observed in three patients of group A
vs. no patients in group B. CONCLUSION: We found that alexandrite laser therapy
is really effective for treating hirsutism. Both shaving and using a scissor for
hair shortening showed similar short-term results, but in one-year follow-up,
paradoxical hypertrichosis was only observed in shaving group and also a lower
hair count was observed in the snipping group.
PMID- 27616193
TI - RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis.
AB - Retinal reactive gliosis is an important pathological feature of diabetic
retinopathy. Identifying the underlying mechanisms causing reactive gliosis will
be important for developing new therapeutic strategies for treating diabetic
retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown
significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a
marked reduction in the release of several cytokines. RNCR3 knockdown alleviates
diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic
retinal cells and ameliorative visual function. RNCR3 knockdown could also
decrease Muller glial cell viability and proliferation, and reduce the expression
of glial reactivity-related genes including GFAP and vimentin in vitro.
Collectively, this study shows that RNCR3 knockdown may be a promising strategy
for the prevention of diabetes mellitus-induced retinal neurodegeneration.
PMID- 27616194
TI - Rapamycin regulates the proliferation of Huh7, a hepatocellular carcinoma cell
line, by up-regulating p53 expression.
AB - Rapamycin, a specific inhibitor of mTOR used extensively as an immunosuppressant,
has been expanded recently to cancer therapy, because the mTOR signal is known to
be up-regulated in various cancer cells including hepatocellular carcinoma (HCC)
cells. In spite of extensive efforts to employ mTOR inhibitors as anti-HCC
therapy, they have not yet been approved by the FDA. Because of the heterogeneity
and complexity of molecular signaling in HCC, suitable biomarkers should be
identified or discovered to improve clinical efficacy of mTOR-specific inhibitors
to HCC cells. In this study, the effect of rapamycin was investigated on two
different HCC cell lines, Huh7 cells and HepG2 cells. Rapamycin was found to
inhibit the proliferation of Huh7 cells but not of HepG2 cells. Moreover, it was
found that rapamycin can up-regulate p53 at the protein level, but not affect its
transcript. To understand the critical role of p53 in the rapamycin effect, knock
down experiments were performed using small-interfering RNAs (siRNAs). The anti
proliferative effect of rapamycin on Huh7 cells clearly disappeared after
blocking p53 production with siRNA, which indicates that p53 is a critical factor
in the anti-proliferative effect of rapamycin in HCC cells. The over-expression
system of p53 was also employed to mimic the effect of rapamycin and found that
cell proliferation was clearly down-regulated by p53 over-expression. Finally, we
found that the extracellular signal-regulated kinase 1/2 (ERK1/2) signal was
regulated by p53 whose expression was induced by rapamycin. Overall, this study
demonstrates that rapamycin inhibited the proliferation of Huh7 cells by up
regulating the expression of p53 and down-regulating the ERK1/2 signal,
indicating that p53 is a useful biomarker for anti-cancer therapy using the
specific inhibitor of mTOR signal, rapamycin, against hepatocellular carcinoma
cells.
PMID- 27616195
TI - Dissection of local Ca(2+) signals inside cytosol by ER-targeted Ca(2+)
indicator.
AB - Calcium (Ca(2+)) is a versatile intracellular second messenger that operates in
various signaling pathways leading to multiple biological outputs. The diversity
of spatiotemporal patterns of Ca(2+) signals, generated by the coordination of
Ca(2+) influx from the extracellular space and Ca(2+) release from the
intracellular Ca(2+) store the endoplasmic reticulum (ER), is considered to
underlie the diversity of biological outputs caused by a single signaling
molecule. However, such Ca(2+) signaling diversity has not been well described
because of technical limitations. Here, we describe a new method to report Ca(2+)
signals at subcellular resolution. We report that OER-GCaMP6f, a genetically
encoded Ca(2+) indicator (GECI) targeted to the outer ER membrane, can monitor
Ca(2+) release from the ER at higher spatiotemporal resolution than conventional
GCaMP6f. OER-GCaMP6f was used for in vivo Ca(2+) imaging of C. elegans. We also
found that the spontaneous Ca(2+) elevation in cultured astrocytes reported by
OER-GCaMP6f showed a distinct spatiotemporal pattern from that monitored by
plasma membrane-targeted GCaMP6f (Lck-GCaMP6f); less frequent Ca(2+) signal was
detected by OER-GCaMP6f, in spite of the fact that Ca(2+) release from the ER
plays important roles in astrocytes. These findings suggest that targeting of
GECIs to the ER outer membrane enables sensitive detection of Ca(2+) release from
the ER at subcellular resolution, avoiding the diffusion of GECI and Ca(2+). Our
results indicate that Ca(2+) imaging with OER-GCaMP6f in combination with Lck
GCaMP6f can contribute to describing the diversity of Ca(2+) signals, by enabling
dissection of Ca(2+) signals at subcellular resolution.
PMID- 27616197
TI - Development and evaluation of a new lateral flow assay for simultaneous detection
of antibodies against African Horse Sickness and Equine Infectious Anemia
viruses.
AB - African horse sickness (AHS) and equine infectious anemia (EIA) are both
notifiable equid specific diseases that may present similar clinical signs.
Considering the increased global movement of horses and equine products over the
past decades, together with the socio-economic impact of previous AHS and EIA
outbreaks, there is a clear demand for an early discrimination and a strict
control of their transmission between enzootic and AHS/EIA-free regions.
Currently, the individual control and prevention of AHS or EIA relies on a series
of measures, including the restriction of animal movements, vector control, and
the use of several laboratory techniques for viral identification, amongst
others. Despite being widely employed in surveillance programmes and in the
control of animal movements, the available serological assays can only detect AHS
or EIA-specific antibodies individually. In this work, a duplex lateral flow
assay (LFA) for simultaneous detection and differentiation of specific antibodies
against AHS virus (AHSV) and EIA virus (EIAV) was developed and evaluated with
experimental and field serum samples. The duplex LFA was based on the AHSV-VP7
outer core protein and the EIAV-P26 major core protein. The results indicated
that the duplex LFA presented a good analytical performance, detecting
simultaneously and specifically antibodies against AHSV and EIAV. The initial
diagnostic evaluation revealed a good agreement with results from the AHS and EIA
tests prescribed by the OIE, and it highlighted the usefulness of the new
AHSV/EIAV duplex LFA for an on-field and point-of-care first diagnosis.
PMID- 27616196
TI - Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA
I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo
controlled trials.
AB - BACKGROUND: In phase 2 trials, lebrikizumab, an anti-interleukin-13 monoclonal
antibody, reduced exacerbation rates and improved FEV1 in patients with
uncontrolled asthma, particularly in those with high concentrations of type 2
biomarkers (eg, periostin or blood eosinophils). We undertook replicate phase 3
studies to assess the efficacy and safety of lebrikizumab in patients with
uncontrolled asthma despite inhaled corticosteroids and at least one second
controller medication. METHODS: Adult patients with uncontrolled asthma, pre
bronchodilator FEV1 40-80% predicted, and stable background therapy were randomly
assigned (1:1:1) with an interactive voice-web-based response system to receive
lebrikizumab 37.5 mg or 125 mg, or placebo subcutaneously, once every 4 weeks.
Randomisation was stratified by screening serum periostin concentration, history
of asthma exacerbations within the last 12 months, baseline asthma medications,
and country. The primary efficacy endpoint was the rate of asthma exacerbations
over 52 weeks in biomarker-high patients (periostin >=50 ng/mL or blood
eosinophils >=300 cells per MUL), analysed with a Poisson regression model
corrected for overdispersion with Pearson chi2 that included terms for treatment
group, number of asthma exacerbations within the 12 months before study entry,
baseline asthma medications, geographic region, screening periostin
concentration, and blood eosinophil counts as covariates. Both trials are
registered at ClinicalTrials.gov, LAVOLTA I, number NCT01867125, and LAVOLTA II,
number NCT01868061. FINDINGS: 1081 patients were treated in LAVOLTA I and 1067
patients in LAVOLTA II. Over 52 weeks, lebrikizumab reduced exacerbation rates in
biomarker-high patients in the 37.5 mg dose group (rate ratio [RR] 0.49 [95% CI
0.34-0.69], p<0.0001) and in the 125 mg dose group (RR 0.70 [0.51-0.95],
p=0.0232) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in
biomarker-high patients in both dose groups versus placebo in LAVOLTA II (37.5
mg: RR 0.74 [95% CI 0.54-1.01], p=0.0609; 125 mg: RR 0.74 [0.54-1.02], p=0.0626).
Pooling both studies, the proportion of patients who experienced treatment
emergent adverse events (79% [1125 of 1432 patients] for both lebrikizumab doses
vs 80% [576 of 716 patients] for placebo), serious adverse events (8% [115
patients] for both lebrikizumab doses vs 9% [65 patients] for placebo), and
adverse events leading to study drug discontinuation (3% [49 patients] for both
lebrikizumab doses vs 4% [31 patients] for placebo) were similar between
lebrikizumab and placebo. The following serious adverse events were reported in
the placebo-controlled period: one event of aplastic anaemia and five serious
adverse events related to raised concentrations of eosinophils in patients
treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo
group. INTERPRETATION: Lebrikizumab did not consistently show significant
reduction in asthma exacerbations in biomarker-high patients. However, it blocked
interleukin-13 as evidenced by the effect on interleukin-13-related
pharmacodynamic biomarkers, and clinically relevant changes could not be ruled
out. FUNDING: F Hoffmann-La Roche.
PMID- 27616198
TI - Single-use, electricity-free amplification device for detection of HIV-1.
AB - Early and accurate diagnosis of HIV is key for the reduction of transmission and
initiation of patient care. The availability of a rapid nucleic acid test (NAT)
for use at the point-of-care (POC) will fill a gap in HIV diagnostics, improving
the diagnosis of acute infection and HIV in infants born to infected mothers. In
this study, we evaluated the performance of non-instrumented nucleic acid
amplification, single-use disposable (NINA-SUD) devices for the detection of HIV
1 in whole blood using reverse-transcription, loop-mediated isothermal
amplification (RT-LAMP) with lyophilized reagents. The NINA-SUD heating device
harnesses the heat from an exothermic chemical reaction initiated by the addition
of saline to magnesium iron powder. Reproducibility was demonstrated between NINA
SUD units and comparable, if not superior, performance for detecting clinical
specimens was observed as compared to the thermal cycler. The stability of the
lyophilized HIV-1 RT-LAMP reagents was also demonstrated following storage at
20, 4, 25, and 30 degrees C for up to one month. The single-use, disposable NAT
minimizes hands-on time and has the potential to facilitate HIV-1 testing in
resource-limited settings or at the POC.
PMID- 27616199
TI - Diapeutic cancer-targeting alkylphosphocholine analogs may advance management of
brain malignancies.
AB - The following is a special report on alkylphosphocholine analogs as targeted
imaging and therapy agents for cancer, and their potential role in diagnosis and
treatment in glioblastoma and brain metastases. These novel cancer-targeting
agents display impressive tumor avidity with low background in the normal brain,
and multimodal diagnostic imaging and therapy capabilities. The use of these
agents may significantly improve diagnosis, treatment and post-treatment follow
up in patients with brain malignancies.
PMID- 27616200
TI - Mercury accumulation in Mediterranean Fish and Cephalopods Species of Sicilian
coasts: correlation between pollution and the presence of Anisakis parasites.
AB - The aim of this study was to investigate mercury accumulation in some species,
caught in Mediterranean Sea, in the period between May and December 2015, and to
compare it to the presence of Anisakis parasites. The samples were examined by
direct mercury analyzer (DMA-80) for their Hg levels. The metal concentration was
compared to the presence or the absence of Anisakis parasites. Significant
differences in Hg concentration in analysed samples were observed. The low
infested fishes contained 1-6 larvae of parasites whereas the high-infested one
had 7-83 larvae.
PMID- 27616201
TI - The role of speckle tracking echocardiography for prognostication in patients
with severe sepsis or septic shock.
PMID- 27616202
TI - Escherichia coli Reduction by Bivalves in an Impaired River Impacted by
Agricultural Land Use.
AB - Fecal indicator bacteria (FIB) are leading causes of impaired surface waters.
Innovative and environmentally appropriate best management practices are needed
to reduce FIB concentrations and associated risk. This study examines the ability
of the native freshwater mussel Anodonta californiensis and an invasive
freshwater clam Corbicula fluminea to reduce concentrations of the FIB
Escherichia coli in natural waters. Laboratory batch experiments were used to
show bivalve species-specific E. coli removal capabilities and to develop a
relationship between bivalve size and clearance rates. A field survey within an
impaired coastal river containing both species of bivalves in an agricultural-
and grazing-dominated area of the central coast of California showed a
significant inverse correlation between E. coli concentration and bivalve
density. An in situ field spiking and sampling study showed filtration by
freshwater bivalves resulting in 1-1.5 log10 reduction of E. coli over 24 h, and
calculated clearance rates ranged from 1.2 to 7.4 L hr-1 bivalve-1. Results of
this study show the importance of freshwater bivalves for improving water quality
through the removal of E. coli. While both native and invasive bivalves can
reduce E. coli levels, the use of native bivalves through integration into best
management practices is recommended as a way to improve water quality and protect
and encourage re-establishment of native bivalve species that are in decline.
PMID- 27616203
TI - A Hiatus of the Greenhouse Effect.
AB - The rate at which the global average surface temperature is increasing has slowed
down since the end of the last century. This study investigates whether this
warming hiatus results from a change in the well-known greenhouse effect. Using
long-term, reliable, and consistent observational data from the Earth's surface
and the top of the atmosphere (TOA), two monthly gridded atmospheric and surface
greenhouse effect parameters (Ga and Gs) are estimated to represent the radiative
warming effects of the atmosphere and the surface in the infrared range from 1979
to 2014. The atmospheric and surface greenhouse effect over the tropical monsoon
prone regions is found to contribute substantially to the global total.
Furthermore, the downward tendency of cloud activity leads to a greenhouse effect
hiatus after the early 1990 s, prior to the warming pause. Additionally, this
pause in the greenhouse effect is mostly caused by the high number of La Nina
events between 1991 and 2014. A strong La Nina indicates suppressed convection in
the tropical central Pacific that reduces atmospheric water vapor content and
cloud volume. This significantly weakened regional greenhouse effect offsets the
enhanced warming influence in other places and decelerates the rising global
greenhouse effect. This work suggests that the greenhouse effect hiatus can be
served as an additional factor to cause the recent global warming slowdown.
PMID- 27616204
TI - How young adults with autism spectrum disorder watch and interpret pragmatically
complex scenes.
AB - The aim of the current study was to investigate subtle characteristics of social
perception and interpretation in high-functioning individuals with autism
spectrum disorders (ASDs), and to study the relation between watching and
interpreting. As a novelty, we used an approach that combined moment-by-moment
eye tracking and verbal assessment. Sixteen young adults with ASD and 16
neurotypical control participants watched a video depicting a complex
communication situation while their eye movements were tracked. The participants
also completed a verbal task with questions related to the pragmatic content of
the video. We compared verbal task scores and eye movements between groups, and
assessed correlations between task performance and eye movements. Individuals
with ASD had more difficulty than the controls in interpreting the video, and
during two short moments there were significant group differences in eye
movements. Additionally, we found significant correlations between verbal task
scores and moment-level eye movement in the ASD group, but not among the
controls. We concluded that participants with ASD had slight difficulties in
understanding the pragmatic content of the video stimulus and attending to social
cues, and that the connection between pragmatic understanding and eye movements
was more pronounced for participants with ASD than for neurotypical participants.
PMID- 27616205
TI - Characterization of the universal stress protein F from atypical enteropathogenic
Escherichia coli and its prevalence in Enterobacteriaceae.
AB - Atypical enteropathogenic Escherichia coli (aEPEC) are heterogeneous strains in
terms of serotypes, adherence patterns and the presence of novel virulence
factors. This heterogeneity is intriguing, promoting studies trying to
characterize these novel proteins and to better comprehend this pathotype group.
In a previous study analyzing low-molecular mass proteomes of four representative
aEPEC strains of three different adhesion phenotypes, we classified proteins
according to their annotated function, with most of them being involved in
metabolism and transport; while some of them were classified as hypothetical
proteins. The majority of the hypothetical proteins were homologue products of
genes identified in the genome of enterohemorrhagic E. coli. One of the
hypothetical proteins was annotated as Z2335, with orthologue in EPEC, and by
bioinformatics analysis, this protein was revealed to be the universal stress
protein F (UspF). Thus, herein we successfully obtained a recombinant UspF
protein from aEPEC, which is a alpha/beta, ATP-binding protein involved in stress
response, with comparable protein production among the four studied strains, but
showing noteworthy differences when cultivated in different stress conditions,
also present in other enterobacterial species, such as Shigella sonnei and
Citrobacter freundii. Furthermore, our results confirm that the Usp protein
superfamily encompasses a conserved group of proteins involved in stress
resistance in aEPEC and other Enterobacteriaceae.
PMID- 27616207
TI - Melatonin and the newborn brain.
AB - Brain injury related to preterm birth and neonatal asphyxia is a leading cause of
childhood neuromotor and cognitive disabilities. Unfortunately, the strategies to
prevent perinatal brain damages remain limited. Among the candidate molecules,
melatonin appears to be one of the most promising agents for its antioxidant and
neuromodulatory action. Robust preclinical evidences and few clinical studies
have suggested a neuroprotective benefit conferred by neonatal exposure to
melatonin. This review recapitulates current basic research, safety and
pharmacokinetic data and ongoing clinical trials on the use of melatonin as a
neuroprotective agent in the newborn.
PMID- 27616206
TI - Endomyocardial proteomic signature corresponding to the response of patients with
dilated cardiomyopathy to immunoadsorption therapy.
AB - : Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left
ventricular ejection fraction (LVEF). Cardiac autoantibodies (AAbs) play a causal
role in the development and progression of DCM. Removal of AAbs using
immunoadsorption (IA/IgG) has been shown as a therapeutic option to improve
cardiac function. However, the response to therapy differs significantly among
patients. The reasons for this variability are not completely understood.
Hitherto, no potential biomarker is available to predict improvement of cardiac
function after therapy accurately. This shotgun proteome study aims to disclose
the differences in the endomyocardial proteome between patients with improved
LVEF after IA/IgG (responders) and those without improvement (non-responders)
before therapy start. Comparative analysis revealed 54 differentially abundant
proteins that were mostly confined to carbohydrate and lipid metabolism, energy
and immune regulation, and cardioprotection. Selected proteins representing
various functional categories were further confirmed by multiple reaction
monitoring (MRM). Among those, protein S100-A8, perilipin-4, and kininogen-1 were
found the most robust candidates differentiating responders and non-responders.
Receiver operating characteristic curve (ROC) analysis of these proteins revealed
highest potential for protein S100-A8 (AUC 0.92) with high sensitivity and
specificity to be developed as a classifier for the prediction of cardiac
improvement after IA/IgG therapy. SIGNIFICANCE: We evaluated the differences in
the myocardial proteome of responder and non-responder DCM patients before
immunoadsorption therapy and identified a number of differentially abundant
proteins involved in energy and lipid metabolism, immune system, and
cardioprotection. MRM was used for verification of results. Proteins S100-A8,
perilipin-4, and kininogen-1 were found to display the largest differences. The
results provide a lead for further studies to screen for protein biomarker
candidates in plasma that might be helpful to stratify patients for
immunoadsorption therapy treatment.
PMID- 27616209
TI - Absence of positive selection on CenH3 in Luzula suggests that holokinetic
chromosomes may suppress centromere drive.
AB - BACKGROUND AND AIMS: The centromere drive theory explains diversity of eukaryotic
centromeres as a consequence of the recurrent conflict between centromeric
repeats and centromeric histone H3 (CenH3), in which selfish centromeres exploit
meiotic asymmetry and CenH3 evolves adaptively to counterbalance deleterious
consequences of driving centromeres. Accordingly, adaptively evolving CenH3 has
so far been observed only in eukaryotes with asymmetric meiosis. However, if such
evolution is a consequence of centromere drive, it should depend not only on
meiotic asymmetry but also on monocentric or holokinetic chromosomal structure.
Selective pressures acting on CenH3 have never been investigated in organisms
with holokinetic meiosis despite the fact that holokinetic chromosomes have been
hypothesized to suppress centromere drive. Therefore, the present study evaluates
selective pressures acting on the CenH3 gene in holokinetic organisms for the
first time, specifically in the representatives of the plant genus Luzula
(Juncaceae), in which the kinetochore formation is not co-localized with any type
of centromeric repeat. METHODS: PCR, cloning and sequencing, and database
searches were used to obtain coding CenH3 sequences from Luzula species. Codon
substitution models were employed to infer selective regimes acting on CenH3 in
Luzula KEY RESULTS: In addition to the two previously published CenH3 sequences
from L. nivea, 16 new CenH3 sequences have been isolated from 12 Luzula species.
Two CenH3 isoforms in Luzula that originated by a duplication event prior to the
divergence of analysed species were found. No signs of positive selection acting
on CenH3 in Luzula were detected. Instead, evidence was found that selection on
CenH3 of Luzula might have been relaxed. CONCLUSIONS: The results indicate that
holokinetism itself may suppress centromere drive and, therefore, holokinetic
chromosomes might have evolved as a defence against centromere drive.
PMID- 27616210
TI - Laboratory comparison of the mechanical properties of TRUShape with several
nickel-titanium rotary instruments.
AB - AIM: To assess and compare the mechanical properties of TRUShape (TRS) with
several nickel-titanium rotary instruments. METHODOLOGY: Cyclic fatigue,
torsional resistance, flexibility and surface microhardness of TRS (size 25,
0.06v taper), ProTaper Next X2 (PTN X2, size 25, 0.06 taper), ProTaper Gold (PTG
F2; size 25, 0.08 taper) and ProTaper Universal (PTU F2; size 25, 0.08 taper)
instruments were evaluated. The topographical structures of the fracture surfaces
of instruments were assessed using a scanning electron microscope. The cyclic
fatigue resistance, torsional resistance and microhardness data were analysed
using one-way analysis of variance (anova) and Tukey's post hoc tests. The
fragment length and bending resistance data were analysed statistically with the
Kruskal-Wallis H-test and Mann-Whitney U-tests. The statistical significance
level was set at P < 0.05. RESULTS: PTN and PTG instruments revealed
significantly higher resistance to cyclic fatigue than TRS and PTU instruments (P
< 0.001). PTN instruments revealed significantly higher torsional resistance
compared with the other instruments (P < 0.001). PTG instrument had significantly
higher flexibility than the other tested brands (P < 0.05). However, for
microhardness, the PTU had significantly higher surface microhardness values
compared with other tested brands (P < 0.05). CONCLUSIONS: TRS instruments had
lower resistance to cyclic fatigue and lower flexibility compared with PTG and
PTN instruments. TRS, PTG and PTU instruments had lower resistance to torsional
stress than PTN instruments. TRS and PTG instruments had comparable surface
microhardness.
PMID- 27616208
TI - Linking hydrogen-mediated boron toxicity tolerance with improvement of root
elongation, water status and reactive oxygen species balance: a case study for
rice.
AB - BACKGROUND AND AIMS: Boron is essential for plant growth but hazardous when
present in excess. As the antioxidant properties of hydrogen gas (H2) were
recently described in plants, oxidative stress induced by excess boron was
investigated along with other biological responses during rice (Oryza sativa)
seed germination to study the beneficial role of H2 METHODS: Rice seeds were
pretreated with exogenous H2 Using physiological, pharmacological and molecular
approaches, the production of endogenous H2, growth status, reactive oxygen
species (ROS) balance and relative gene expression in rice were measured under
boron stress to investigate mechanisms of H2-mediated boron toxicity tolerance.
KEY RESULTS: In our test, boron-inhibited seed germination and seedling growth,
and endogenous H2 production, were obviously blocked by exogenously applying H2
The re-establishment of ROS balance was confirmed by reduced lipid peroxidation
and ROS accumulation. Meanwhile, activities of catalase (CAT) and peroxidase
(POX) were increased. Suppression of pectin methylesterase (PME) activity and
downregulation of PME transcripts by H2 were consistent with the alleviation of
root growth inhibition caused by boron. Water status was improved as well. This
result was confirmed by the upregulation of genes encoding specific aquaporins
(AQPs), the maintenance of low osmotic potential and high content of soluble
sugar. Increased transcription of representative AQP genes (PIP2;7 in particular)
and BOR2 along with decreased BOR1 mRNA may contribute to lowering boron
accumulation. CONCLUSIONS: Hydrogen provides boron toxicity tolerance mainly by
improving root elongation, water status and ROS balance.
PMID- 27616211
TI - Multicenter registry on inflammatory myositis from the Rheumatology Society in
Madrid, Spain: Descriptive Analysis.
AB - OBJECTIVE: To analyze clinical characteristics, survival and causes of death of
patients diagnosed with autoimmune inflammatory myositis in the REMICAM registry
from the Society of Rheumatology in the Community of Madrid (SORCOM). METHODS:
Multicenter cohort of patients diagnosed with autoimmune inflammatory myopathy
with follow-up between January 1980 and December 2014. A total of 313 variables
concerning demographic, clinical and morbidity data were collected, and a
comparison was performed between clinical subgroups. RESULTS: A total of 479
patients were recruited from 12 centers, with 14% of patients lost to follow-up.
Seventy-four percent of cases were women, age at diagnosis of 44+/-23 years and a
mean follow-up period of 10+/-8 years. The most frequent clinical subgroups were
primary myositis (PM 29%, DM 22%), followed by overlap myositis (20.5%), juvenile
myositis (18%), myositis associated with cancer (8%), immune-mediated necrotizing
myositis (1%) and inclusion body myositis (1%). During the follow-up period, a
total of 114 deaths (28%) were registered, the main causes being cancer (24%),
infections (23%) and cardiovascular events (21%). CONCLUSIONS: A total of 479
patients were recruited in the REMICAM registry of inflammatory myopathies.
Including sociodemographic, clinical and prognostic information, it represents
the largest Spanish multicenter registry to date in rheumatology, and constitutes
an important source for conducting further substudies.
PMID- 27616212
TI - Autoimmune pitfalls in treatment with TNFalpha inhibitors.
PMID- 27616213
TI - Effects of eCG are more pronounced in primiparous than multiparous Bos indicus
cows submitted to a timed artificial insemination protocol.
AB - The effects of eCG on follicular growth, ovulation, and pregnancy per artificial
insemination (P/AI) in multiparous and primiparous Bos indicus beef cows
submitted to timed artificial insemination (TAI) were evaluated in three
experiments. In experiments 1 (follicular responses; n = 64), 2 (follicular
growth and ovulation rate; n = 662), and 3 (P/AI; n = 2092), cows submitted to
TAI were assigned to receive one of two treatments on Day 8 of the
synchronization protocol: control (no additional treatment) or eCG (300-IU of eCG
intramuscularly). In experiment 1, largest follicle (LF) diameter on Day 8 (P =
0.56) and the interval from progesterone (P4)-device removal to ovulation (P =
0.79) did not differ between treatments. However, the maximum diameter of the LF
(P = 0.05) and ovulation rate (P = 0.03) were greater in cows that received eCG.
In experiment 2, the diameter of the LF on Day 10, follicular growth, and
ovulation rate were greater in eCG-treated cows (P < 0.01). However, CL diameter
was similar between treatments (P = 0.11). In experiment 3, there was a treatment
by-parity interaction (P = 0.003) on P/AI, such that treatment with eCG was more
effective in primiparous cows. In conclusion, eCG treatment resulted in increased
final follicular growth, ovulation rate, and fertility in B indicus cows
submitted to TAI protocols, especially in primiparous cows.
PMID- 27616214
TI - Environmental and animal factors associated with gestation length in Holstein
cows and heifers in two herds in the Czech Republic.
AB - The objective was to assess the effects of the month of conception, month of
calving, sex of the calf, and twins on gestation length (GL) in Holstein cows and
heifers in two dairy herds with different milk yields. The study was performed in
northeast Czech Republic over a 6-year period on two commercial dairy herds with
a mean annual milk production of 11,060 kg per cow in the higher milk-producing
herd and 8854 kg per cow in the lower milk-producing herd. Gestation length in
cows that conceived in different months of the year was longer in the higher milk
producing herd than that in the lower milk-producing herd throughout the year (P
< 0.01), whereas GL in heifers was almost the same in both herds. Gestation
length in cows that conceived in different months of the year was longer than
that in heifers through the whole year in both herds (P < 0.05). Similar results
were found in cows and heifers that calved in different months of the year.
Gestation length in cows and heifers that conceived in the first months of the
year was longer than in those that conceived in the last months of the year in
both herds (P < 0.05). Gestation length in cows and heifers that calved in late
fall and throughout winter was longer than in those that calved in spring and
summer in both herds (P < 0.05). Gestation length in females carrying male calves
was longer than in those carrying female calves (P < 0.0001). Gestation length in
cows (P < 0.0001) and heifers (P < 0.05) carrying singles was longer than in
those carrying twins in both herds. In conclusion, results indicate that GL in
Holstein cattle is associated with the month of conception, month of calving,
herd, parity, sex of the calf, and twins.
PMID- 27616215
TI - Fish sperm subpopulations: Changes after cryopreservation process and
relationship with fertilization success in tambaqui (Colossoma macropomum).
AB - Fish tambaqui (Colossoma macropomum) is the native Brazilian fish with the
highest agricultural production under intensive aquaculture in South America.
However, the decrease in the genetic variability in fish farms has become
necessary the improvement of cryopreservation process through new statistical
studies of spermatozoa (like subpopulation studies). The evaluation of the
kinetic data obtained with a computer-assisted sperm analysis system, applying a
two-step cluster analysis, yielded in tambaqui three different subpopulations in
fresh sperm: SP1, considered as a slow nonlinear subpopulation; SP2, considered
as a fast nonlinear subpopulation, and finally; SP3, considered as a fast linear
subpopulation. For cryopreserved sperm, the cluster analysis yielded only two
sperm subpopulations: SP1', considered as a slow nonlinear subpopulation and
SP2', which seemed to be an intermediate subpopulation (showing medium motility
and velocity values) merged from SP2 and SP3 obtained from fresh sperm.
Coefficients of correlation (r) and determination (r2) between the sperm
subpopulations from fresh sperm and the fertilization rates were calculated, and
SP2 and SP3 (the fast-spermatozoa subpopulations) showed a high-positive
correlation with the fertilization rates (r = 0.93 and 0.79, respectively). In
addition, the positive significant correlations found in curvilinear velocity (r
= 0.78), straight line velocity (r = 0.57), and average velocity (r = 0.75)
indicate that sperm kinetic features seem to be a key factor in the fertilization
process in tambaqui, as occur in other fish species.
PMID- 27616216
TI - FSH stimulation of anestrous cats improves oocyte quality and development of
parthenogenetic embryos.
AB - In the domestic cat, the efficiency of in vitro embryo production systems is
negatively affected during the nonbreeding season. The objective of this research
was to evaluate the effect of FSH stimulation in anestrous cats, on quality of
cumulus-oocyte complexes (COCs) and in vitro developmental competence after
parthenogenetic activation. To accomplish this purpose, anestrous cats were
grouped into: (1) FSH treated (serial doses of 5 mg of porcine FSH each, every 24
hours, for 4 days) and (2) untreated control. The COCs were classified
morphologically and a proportion of grade I and II COCs was used for expression
analysis of FSHR, LHCGR, EGFR, PTGS2, EGR1, GDF9, and GATM by RT-qPCR. In
addition, another proportion of grade I and II COCs was matured in vitro and used
for parthenogenetic activation. After 8 days in culture, blastocyst and hatching
blastocyst rates were assessed, and the expression of OCT4, SOX2, NANOG, CDX2,
and GATA6 was evaluated. The COCs in the FSH group had an enhanced quality, a
higher expression of LHCGR and a lower expression of GATM than did COCs from the
control group (P < 0.05). Furthermore, embryos in the FSH group had increased
blastocyst and hatching blastocyst rates, and those embryos had a higher
expression of OCT4 and GATA than their counterparts from the control group (P <
0.05). In conclusion, ovarian stimulation of anestrous cats with FSH improved
quality and increased the expression of LHCGR in COCs. The enhanced in vitro
developmental competence, after parthenogenetic activation of oocytes from FSH
treated cats, coincided with an increased expression of OCT4 and GATA6 in
blastocysts and hatching blastocysts.
PMID- 27616218
TI - Solvent-Free Ring-Opening Metathesis Polymerization of Norbornene over Silica
Supported Tungsten-Oxo Perhydrocarbyl Catalysts.
AB - Ring opening metathesis polymerization (ROMP) of bicyclo[2.2.1]hept-2-ene
(norbornene) is carried out over silica-supported catalysts based on tungsten
complexes bearing an oxo ligand (1: [(?SiO)W(?O)(CH2 SiMe3 )3 , 2:
[(?SiO)W(?O)(?CHCMe2 Ph)(dAdPO)], dAdPO ? 2,6 diadamantyl-4-methylphenoxide, 3:
[(?SiO)2 W(?O)(CH2 SiMe3 )2 ]). The evaluation of the catalytic activities of the
aforementioned materials in ROMP indicates that at low reaction time (0.5 min),
the highest polymer yield is obtained with catalyst 2. However, for longer
reaction time (>2 min), complex 3, a model of the industrial catalyst, exhibits a
better monomer conversion. The polymers obtained are characterized. Moreover,
these catalysts are shown to be rather preferentially selective to give the cis
polynorbornene (>65%), characterized by high melting points (~300 degrees C).
The experimental values of the average molecular weight (Mn ) of polynorbornenes
are found to be close to the theoretical ones for the polymers prepared using
catalyst 2 and higher for those originated from catalyst 3.
PMID- 27616217
TI - Family-centered brief intervention for reducing obesity and cardiovascular
disease risk: A randomized controlled trial.
AB - OBJECTIVE: To assess the effects of a family-centered, physical activity and
nutrition "brief" intervention (time-limited contact) on body weight and related
health outcomes in primary health care patients with an elevated 5-year
cardiovascular disease (CVD) risk. METHODS: This study implemented a cluster
randomized controlled trial design with two treatment conditions: a CVD risk
assessment and one-time consultation ("usual care" control) and a CVD risk
assessment and up to five home sessions that aimed to reduce obesity by
encouraging physical activity and healthy eating (intervention). Three hundred
and twenty patients aged 35 to 65 years from 16 primary health care clinics in
Auckland, New Zealand, participated in the study. Intervention effects on BMI,
waist circumference, blood pressure, blood cholesterol, triglycerides, 5-year CVD
risk, physical activity, and dietary patterns were assessed using generalized
linear mixed models. RESULTS: When compared with the control group, the
intervention resulted in a significant but relatively modest decrease in BMI
between baseline and the 12-month follow-up (-0.633 kg m-2 , Padj = 0.048).
Significant decreases were also observed for total cholesterol at 4 and 12
months, the total cholesterol to high-density lipoprotein cholesterol ratio at 4
months, 5-year CVD risk at 4 months, and fast food consumption at 12 months.
CONCLUSIONS: Our findings show that a family-centered brief intervention
targeting physical activity and nutrition can generate slightly better obesity
related health outcomes than usual care alone.
PMID- 27616268
TI - Continuous three dimensional analysis of running mechanics during a marathon by
means of inertial magnetic measurement units to objectify changes in running
mechanics.
AB - Recent developments in wearable and wireless sensor technology allow for a
continuous three dimensional analysis of running mechanics in the sport specific
setting. The present study is the first to demonstrate the possibility of
analyzing three dimensional (3D) running mechanics continuously, by means of
inertial magnetic measurement units, to objectify changes in mechanics over the
course of a marathon. Three well trained male distance runners ran a marathon
while equipped with inertial magnetic measurement units on trunk, pelvis, upper
legs, lower legs and feet to obtain a 3D view of running mechanics and to asses
changes in running mechanics over the course of a marathon. Data were
continuously recorded during the entire 42.2km (26.2Miles) of the Marathon. Data
from the individual sensors were transmitted wirelessly to a receiver, mounted on
the handlebar of an accompanying cyclist. Anatomical calibration was performed
using both static and dynamic procedures and sensor orientations were thus
converted to body segment orientations by means of transformation matrices
obtained from the segment calibration. Joint angle (hip, knee and ankle)
trajectories as well as center of mass (COM) trajectory and acceleration were
derived from the sensor data after segment calibration. Data were collected and
repeated measures one way ANOVA's, with Tukey post-hoc test, were used to
statistically analyze differences between the defined kinematic parameters (max
hip angle, peak knee flexion at mid-stance and at mid-swing, ankle angle at
initial contact and COM vertical displacement and acceleration), averaged over
100 strides, between the first and the last stages (8 and 40km) of the marathon.
Significant changes in running mechanics were witnessed between the first and the
last stage of the marathon. This study showed the possibility of performing a 3D
kinematic analysis of the running technique, in the sport specific setting, by
using inertial magnetic measurement units. For the three runners analyzed,
significant changes were observed in running mechanics over the course of a
marathon. The present measurement technique therefore allows for more in-depth
study of running mechanics outside the laboratory setting.
PMID- 27616269
TI - Risk communication in the case of the Fukushima accident: Impact of communication
and lessons to be learned.
AB - Risk communication about the Fukushima Daiichi nuclear power plant accident in
2011 was often not transparent, timely, clear, nor factually correct. However,
lessons related to risk communication have been identified and some of them are
already addressed in national and international communication programmes and
strategies. The Fukushima accident may be seen as a practice scenario for risk
communication with important lessons to be learned. As a result of risk
communication failures during the accident, the world is now better prepared for
communication related to nuclear emergencies than it was 5 years ago The present
study discusses the impact of communication, as applied during the Fukushima
accident, and the main lessons learned. It then identifies pathways for
transparent, timely, clear and factually correct communication to be developed,
practiced and applied in nuclear emergency communication before, during, and
after nuclear accidents. Integr Environ Assess Manag 2016;12:683-686. (c) 2016
SETAC.
PMID- 27616267
TI - Soil bacteria as sources of virulence signal providers promoting plant infection
by Phytophthora pathogens.
AB - Phytophthora species are known as "plant destroyers" capable of initiating single
zoospore infection in the presence of a quorum of chemical signals from the same
or closely related species of oomycetes. Since the natural oomycete population is
too low to reach a quorum necessary to initiate a disease epidemic, creation of
the quorum is reliant on alternate sources. Here, we show that a soil bacterial
isolate, Bacillus megaterium Sb5, promotes plant infection by Phytophthora
species. In the presence of Sb5 exudates, colonization of rhododendron leaf discs
by 12 Phytophthora species/isolates was significantly enhanced, single zoospores
of P. nicotianae infected annual vinca and P. sojae race 25 successfully attacked
a non-host plant, Nicotiana benthamiana as well as resistant soybean cultivars
with RPS1a or RPS3a. Sb5 exudates, most notably the fractions larger than 3 kDa,
promoted plant infection by improving zoospore swimming, germination and plant
attachment. Sb5 exudates also stimulated infection hypha growth and upregulated
effector gene expression. These results suggest that environmental bacteria are
important sources of virulence signal providers that promote plant infection by
Phytophthora species, advancing our understanding of biotic factors in the
environmental component of the Phytophthora disease triangle and of communal
infection of plant pathogens.
PMID- 27616270
TI - Difference in risk assessment for development of contrast-induced acute kidney
injury using the MDRD versus CKD-EPI equations to estimate glomerular filtration
rate.
PMID- 27616272
TI - Colloidal gold-McAb probe-based rapid immunoassay strip for simultaneous
detection of fumonisins in maize.
AB - BACKGROUND: Fumonisins are a kind of toxic and carcinogenic mycotoxin. A rapid
immunochromatographic test strip has been developed for simultaneous detection of
fumonisin B1 , B2 and B3 (FB1 , FB2 and FB3 ) in maize based on colloidal gold
labelled monoclonal antibody (McAb) against FB1 probe. RESULTS: The anti-FB1 McAb
(2E11-H3) was produced through immunisation and cell fusion, and identified as
high affinity, specificity and sensitivity. The cross-reaction ratios with
fumonisin B2 and B3 were accordingly 385% and 72.4%, while none with other
analogues. The colloid gold-labelled anti-FB1 McAb probe was successfully
prepared and used for establishing the immunochromatographic strip. The test
strip showed high sensitivity and specificity, the IC50 for FB1 was 58.08 ng mL-1
, LOD was 11.24 ng mL-1 , calculated from standard curve. Moreover, the test
strip exhibited high cross-reactivity with FB2 and FB3 , and could be applied to
the simultaneous detection of FBs (FB1 :FB2 :FB3 = 12:4:1) in maize sample with
high accuracy and precision. The average recoveries of FBs in maize ranged from
90.42% to 95.29%, and CVs were 1.25-3.77%. The results of the test strip for FBs
samples showed good correlation with high-performance liquid chromatography
analysis. CONCLUSION: The immunochromatographic test strip could be employed in
the rapid simultaneous detection of FB1 , FB2 and FB3 in maize samples on-site.
(c) 2016 Society of Chemical Industry.
PMID- 27616271
TI - Effect of sildenafil on human aromatase activity: From in vitro structural
analysis to catalysis and inhibition in cells.
AB - Aromatase catalyses the conversion of androgens into estrogens and is a well
known target for breast cancer therapy. As it has been suggested that its
activity is affected by inhibitors of phosphodiesterase-5, this work investigates
the potential interaction of sildenafil with aromatase. This is carried out both
at molecular level through structural and kinetics assays applied to the purified
enzyme, and at cellular level using neuronal and breast cancer cell lines.
Sildenafil is found to bind to aromatase with a KD of 0.58+/-0.05MUM acting as a
partial and mixed inhibitor with a maximal inhibition of 35+/-2%. Hyperfine
sublevel correlation spectroscopy and docking studies show that sildenafil binds
to the heme iron via its 6th axial water ligand. These results also provide
information on the starting molecular scaffold for the development of new
generations of drugs designed to inhibit aromatase as well as phosphodiesterase
5, a new emerging target for breast cancer therapy.
PMID- 27616273
TI - Intra-articular Hyaluronic Acid in Treating Knee Osteoarthritis: a PRISMA
Compliant Systematic Review of Overlapping Meta-analysis.
AB - Numerous meta-analyses have been conducted aiming to compare hyaluronic acid (HA)
and placebo in treating knee osteoarthritis (OA). Nevertheless, the conclusions
of these meta-analyses are not in consistency. The purpose of the present study
was to perform a systematic review of overlapping meta-analyses investigating the
efficacy and safety of HA for Knee OA and to provide treatment recommendations
through the best evidence. A systematic review was conducted based on the PRISMA
guidelines. The meta-analyses and/or systematic reviews that compared HA and
placebo for knee OA were identified. AMSTAR instrument was used to evaluate the
methodological quality of individual study. The information of heterogeneity
within each variable was fetched for the individual studies. Which meta-analyses
can provide best evidence was determined according to Jadad algorithm. Twelve
meta-analyses met the eligibility requirements. The Jadad decision making tool
suggests that the highest quality review should be selected. As a result, a high
quality Cochrane review was included. The present systematic review of
overlapping meta-analyses demonstrates that HA is an effective intervention in
treating knee OA without increased risk of adverse events. Therefore, the present
conclusions may help decision makers interpret and choose among discordant meta
analyses.
PMID- 27616274
TI - Clinical presentations, risk factors and outcomes of ceftazidime-resistant Gram
negative endophthalmitis.
AB - BACKGROUND: To describe the clinical features and outcomes of patients diagnosed
with ceftazidime-resistant Gram-negative endophthalmitis and the role of
intravitreal imipenem in these cases. DESIGN: Retrospective consecutive
interventional case series at a tertiary eye care centre in South India.
PARTICIPANTS: Consecutive cases of ceftazidime-resistant Gram-negative
endophthalmitis from April 2010 to December 2014. Fifty-six cases diagnosed
during this time period were included. METHODS: All cases were managed with
vitreous biopsy/vitrectomy, microscopy and undiluted vitreous culture,
antimicrobial susceptibility of bacterial isolates and received intravitreal
antibiotics. MAIN OUTCOME MEASURES: Anatomic and visual outcome of these cases,
antimicrobial susceptibility pattern of intravitreal imipenem and outcome of
cases injected with it. RESULTS: Commonest presentation was acute endophthalmitis
following cataract surgery (27 eyes, 48.21%). Pseudomonas aeruginosa was isolated
in 33 eyes (58.93%; 95% CI 46.05-71.81%). Nineteen eyes (34%; 95% CI 21.59
46.41%) developed phthisis; 14 eyes (25%; 95% CI 13.66-36.34%) had vision
<20/200; 17 eyes (30.35%; 95% CI 18.31-42.39%) eyes had an ambulatory vision
>20/200 (logMAR 1); 6 eyes (10.71%; 95% CI 2.61-18.81%) had a reading vision
>20/40 (logMAR 0.3). Trend was towards better anatomic (72.73% vs. 40%) (P =
0.05) and visual improvement in the imipenem group (logMAR 3.94 + 0.21 to 2.43 +
1.4; P = 0.002), as compared with non-imipenem group (logMAR 2.99 + 1.3 to 2.55 +
1.4; P = 0.13). CONCLUSIONS: Outcome of ceftazidime-resistant Gram-negative
endophthalmitis is poor. P. aeruginosa is the commonest isolated organism. All
cases were sensitive to imipenem. There was a trend towards better anatomic
outcome in imipenem-treated eyes.
PMID- 27616275
TI - Angiotensin II-Induced Apoptosis of Human Umbilical Vein Endothelial Cells was
Inhibited by Blueberry Anthocyanin Through Bax- and Caspase 3-Dependent Pathways.
AB - BACKGROUND This study aimed to investigate the inhibitory effect of blueberry
anthocyanin (BBA) on Angiotensin II (Ang II)-induced apoptosis of human umbilical
vein endothelial cells (HUVECs), and its regulation mechanisms involving Bax and
Caspase 3. MATERIAL AND METHODS HUVECs were first treated by different
concentrations of Ang II (10-9, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L) and BBA
(80, 40, 20, 10, 5, and 2.5 MUg/ml). After 24 h and 48 h of treatment, MTT was
performed to detect the viability of HUVECs. Then, HUVECs were randomly divided
into the Ang II group (10-6 mol/L Ang II) and Ang II + BBA group (10-6 mol/L Ang
II and 20 MUg/ml BBA), and the apoptosis rate was detected by flow cytometry.
Western blot analysis was performed to detect the expression of Bax and Caspase 3
in these 2 groups. During the whole process, HUVECs without any treatments served
as the control group. RESULTS The cell viability of HUVECs was significantly
reduced by Ang II in a time- and concentration-dependent manner (P<0.05), while
BBA significantly elevated the cell viability of HUVECs until a peak of 20.0
MUg/ml. The apoptosis rate of HUVECs was significantly increased by Ang II
(P<0.01) and reduced by the BBA intervention (P<0.05). Ang II significantly
elevated the expression of Bax and Caspase 3 in HUVECs, but their expression was
significantly inhibited by BBA. CONCLUSIONS BBA increased cell viability and
reduced apoptosis rate of HUVECs induced by Ang II through Bax- and Caspase 3
dependent pathways.
PMID- 27616276
TI - Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral
nociception and hypersensitivity.
AB - Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+
permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory
bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2
is important for visceral nociception and the development of visceral
hypersensitivity. Therefore, we investigated the expression of TRPM2 channels and
their involvement in visceral nociception in normal physiology and under
pathological conditions that cause visceral hypersensitivity in rats. TRPM2
immunoreactivities were detected in the mucosa and muscle layer of the rat
gastrointestinal tract. TRPM2 immunopositive cell bodies were almost completely
co-localized with calretinin- and NeuN-positive cells in the myenteric plexus. We
found that the majority of the TRPM2-immunoreactive cells were double-labeled
with the retrograde marker fluorogold in lumbar 6/sacral 1 dorsal root ganglia
(DRG), indicating that TRPM2 is expressed in spinal primary afferents innervating
the distal colon. Subtypes of TRPM2-immunopositive DRG neurons were labeled by
the A-fiber marker NF200, the C-fiber marker IB4, substance P, calcitonin gene
related peptide, or P2X3 receptor. We found that oral administration of the TRPM2
inhibitor econazole (30mg/kg) reduced the visceromotor response (VMR) to noxious
colorectal distention (CRD) at 80mmHg in control rats. Expression of TRPM2 in the
mucosa of the distal colon was increased in a trinitrobenzene sulfonic acid
induced colitis model. The VMR to CRD significantly increased in colitis model
rats compared with control rats at 40, 60, and 80mmHg. Econazole restored
visceral hypersensitivity to the control level. Furthermore, TRPM2-deficient mice
showed significantly attenuated trinitrobenzene sulfonic acid induced visceral
hypersensitivity compared with wild-type mice. In conclusion, TRPM2 channels
contribute to visceral nociception in response to noxious stimuli under normal
conditions and visceral hypersensitivity in pathological conditions.
PMID- 27616277
TI - The reversal of multidrug resistance in ovarian carcinoma cells by co-application
of tariquidar and paclitaxel in transferrin-targeted polymeric micelles.
AB - In this study, a transferrin (Tf)-modified polyethylene glycol-phosphatidyl
ethanolamine (PEG-PE)-based micellar delivery system containing paclitaxel (PTX)
and tariquidar (TRQ), a potent third generation P-gp inhibitor, was prepared. The
nanoformulation was evaluated by targeting efficiency, cellular association,
cellular internalization pathway and cytotoxicity for reversal of PTX resistance
on two multidrug resistant (MDR) ovarian carcinoma cell lines, SKOV-3TR and A2780
Adr. PTX and TRQ are both hydrophobic compounds. They were successfully
encapsulated into the micellar structure containing vitamin E as the
encapsulation enhancer. The Tf-targeted micelles were internalized mainly via
clathrin-dependent endocytosis by both cell lines. For SKOV-3TR, additional
mechanisms including caveolin-dependent endocytosis and macropinocytosis were
found to play a significant role. The PTX cytotoxicity against the SKOV-3TR and
A2780-Adr MDR cells was increased significantly in the presence of micellar
encapsulation. However, unlike the A2780-Adr cell line, the Tf-targeting effect
was significant on SKOV-3TR cells when co-administrated with TRQ. Penetration of
the Tf-targeted micelles in a cancer cell spheroid culture was also investigated.
PMID- 27616278
TI - Use of imaging in diagnosis of Herlyn-Werner-Wunderlich syndrome, a case report.
PMID- 27616279
TI - Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a
comparison across three assays.
AB - CONTEXT: The short ACTH stimulation test (250 MUg) is the dynamic test most
frequently used to assess adrenal function. It is possible that a single basal
cortisol could be used to predict the dynamic response, but research has been
hampered by the use of different assays and thresholds. OBJECTIVE: To propose a
morning baseline cortisol criterion of three of the most commonly used modern
cortisol immunoassays - Advia Centaur (Siemens), Architect (Abbott) and the Roche
Modular System (Roche) - that could predict adrenal sufficiency. DESIGN:
Observational, retrospective cross-sectional study at two centres. PATIENTS AND
MEASUREMENTS: Retrospective analysis of the results of 1019 Short Synacthen tests
(SSTs) with the Advia Centaur, 449 SSTs with the Architect and 2050 SSTs with the
Roche Modular System assay. Serum cortisol levels were measured prior to
injection of 250 MUg Synacthen and after 30 min. Overall, we were able to collate
data from a total of 3518 SSTs in 3571 patients. RESULTS: Using receiver-operator
curve analysis, baseline cortisol levels for predicting passing the SST with 100%
specificity were 358 nmol/l for Siemens, 336 nmol/l for Abbott and 506 nmol/l for
Roche. Utilizing these criteria, 589, 158 and 578 SSTs, respectively, for
Siemens, Abbott and Roche immunoassays could have been avoided. CONCLUSIONS: We
have defined assay-specific morning cortisol levels that are able to predict the
integrity of the hypothalamo-pituitary-adrenal axis. We propose that this
represents a valid tool for the initial assessment of adrenal function and has
the potential to obviate the need for dynamic testing in a significant number of
patients.
PMID- 27616280
TI - Interactions of surface-displayed glycolytic enzymes of Mycoplasma pneumoniae
with components of the human extracellular matrix.
AB - Mycoplasma pneumoniae is a major cause of community-acquired respiratory
infections worldwide. Due to the strongly reduced genome, the number of virulence
factors expressed by this cell wall-less pathogen is limited. To further
understand the processes during host colonization, we investigated the
interactions of the previously confirmed surface-located glycolytic enzymes of M.
pneumoniae (pyruvate dehydrogenase A-C [PdhA-C], glyceraldehyde-3-phosphate
dehydrogenase [GapA], lactate dehydrogenase [Ldh], phosphoglycerate mutase [Pgm],
pyruvate kinase [Pyk] and transketolase [Tkt]) to the human extracellular matrix
(ECM) proteins fibrinogen (Fn), fibronectin (Fc), lactoferrin (Lf), laminin (Ln)
and vitronectin (Vc), respectively. Concentration-dependent interactions between
Fn and Vc and all eight recombinant proteins derived from glycolytic enzymes,
between Ln and PdhB-C, GapA, Ldh, Pgm, Pyk and Tkt, between Lf and PdhA-C, GapA
and Pyk, and between Fc and PdhC and GapA were demonstrated. In most cases, these
associations are significantly influenced by ionic forces and by polyclonal sera
against recombinant proteins. In immunoblotting, the complex of human
plasminogen, activator (tissue-type or urokinase plasminogen activator) and
glycolytic enzyme was not able to degrade Fc, Lf and Ln, respectively. In
contrast, degradation of Vc was confirmed in the presence of all eight enzymes
tested. Our data suggest that the multifaceted associations of surface-localized
glycolytic enzymes play a potential role in the adhesion and invasion processes
during infection of human respiratory mucosa by M. pneumoniae.
PMID- 27616281
TI - Potential of combination therapy of endolysin MR-10 and minocycline in treating
MRSA induced systemic and localized burn wound infections in mice.
AB - MRSA is the predominant pathogen responsible for fatal burn wound infection in
patients. Antibiotic resistance and its ability to form biofilms on the surface
of burn wounds limit the use of antibiotics to contain this pathogen. The results
of present study have shown that single dose of combination therapy of endolysin
MR-10 (50MUg/s.c) and minocycline (50mg/kg/orally) resulted in 100% survival of
group of mice with systemic MRSA infection. Maximum reduction in bacterial load
in various organs was observed in the group that received combination therapy. In
comparison to control, a significant reduction (p<0.01) of 4.82, 1.81, 1.51, 1.2
logs was observed in skin, blood, liver and spleen respectively, by 3rd day post
infection. As a result of which, all organs became sterile thereby protecting
mice from mortality. Histopathological analysis corroborated our findings showing
no signs of inflammation and bacterial infection in the group that received
combination therapy. Treatment of localized burn wound infection with combination
therapy resulted in early resolution of infection followed by fast healing. The
group that received combination therapy showed complete resolution of infection
in less than 10days. Moreover, the skin samples obtained from animals treated
with combination therapy showed no myeloperoxidase (MPO) activity on 10th day
post treatment. In combination therapy group, ~98% wound contraction was observed
by 12th day followed by complete closure of wound within ~14days. The
histopathological analysis showed no signs of inflammation and infection.
Collagen staining revealed early signs of re-epithelization of epidermis and
signs of collagen regeneration in-group that received combination therapy. Hence,
this study suggests that the combined therapy of endolysin MR-10 and minocycline
is a better option in controlling burn wound infections.
PMID- 27616282
TI - Staphylococcus aureus PSM peptides induce tolerogenic dendritic cells upon
treatment with ligands of extracellular and intracellular TLRs.
AB - Dendritic cells (DCs) are key players of the immune system and thus a target for
immune evasion by pathogens. We recently showed that the virulence factor phenol
soluble modulin (PSM) produced by community-associated methicillin-resistant
Staphylococcus aureus strains induces tolerogenic DCs upon Toll-like receptor
(TLR) 2 activation via the p38-CREB-IL-10 pathway. Here, we addressed the
question whether this tolerogenic phenotype of DCs induced by PSMs is specific
for TLR2 activation. Therefore, bone marrow-derived DCs were treated with various
ligands for extracellular and intracellular TLRs simultaneously with PSMalpha3.
We show that PSMalpha3 modulates antigen uptake, maturation and cytokine
production of DCs activated by TLR1/2, TLR2/6, TLR4, TLR7, and TLR9. Pre
incubation of DCs with a p38 MAP kinase inhibitor prevented the PSMalpha3-induced
IL-10 secretion, as well as MHC class II up-regulation upon TLR activation. In
consequence, the tolerogenic DCs induced by PSMalpha3 in response to several TLR
ligands promoted priming of regulatory T cells. Thus, PSMs could be useful as
inducers of tolerogenic DCs upon TLR ligand stimulation for therapeutic
applications.
PMID- 27616284
TI - Diverse multi-organ histopathologic changes in a failed Fontan patient.
AB - We report multi-organ histopathological changes in a patient with protein-losing
enteropathy (PLE) over 12 years after Fontan operation. A 14-year-old boy with
right isomerism heart and single ventricle had undergone Fontan procedure at 19
months of age, and PLE was diagnosed at 28 months. He had several episodes of
intestinal bleeding and pre-renal failure with elevated creatine, and eventually
died of pneumonia. The intrapulmonary small arteries showed medial and intimal
thickening resembling pulmonary hypertension. No major ulcerative lesions were
found in the small or large intestines. Dilated lymph ducts, one of the
characteristic features of PLE, were not seen in mucosal and submucosal areas.
Liver cirrhosis was obvious despite little increase in liver enzymes.
Histological changes in bilateral kidneys were subtle despite repeated episodes
of renal failure. Thus, there may be significant discrepancies between clinical
manifestations and multi-organ histological changes in failed Fontan patients.
PMID- 27616283
TI - Combination of density gradient centrifugation and swim-up methods effectively
decreases morphologically abnormal sperms.
AB - Density gradient centrifugation (DGC) and swim-up techniques have been reported
for semen preparation in assisted reproductive techniques in humans. We
investigated whether semen preparation using a combination of DGC and swim-up
techniques could effectively decrease morphologically abnormal human sperms at
the ultrastructural level. Semen samples were obtained from 16 infertile males
and fractionated by swim-up following DGC. Ultrastructural abnormalities of
sperms obtained from original semen, lower layer of swim-up following DGC, and
upper layer of swim-up following DGC were analyzed by transmission electron
microscopy. The correlation among ultrastructural head abnormality in sperms from
the upper layer of swim-up, fertilization in in vitro fertilization, and
pregnancy after embryo transfer was also investigated. Furthermore, sperms with
DNA fragmentation in the samples processed via a combination of DGC and swim-up
was assessed in a sperm chromatin structure assay. Ultrastructural abnormalities
in sperm heads and tails in the upper layer after swim-up following DGC was the
lowest among the three groups. Sperms with nuclear vacuoles were the most
difficult to eliminate using a combination of DGC and swim-up in all types of
head abnormalities. A negative correlation was confirmed between the
fertilization rates of intracytoplasmic sperm injection and head abnormality of
sperms obtained from the upper layer of the swim-up following DGC. Sperms with
DNA fragmentation were effectively decreased using the combination of two
techniques. In conclusion, the combination of DGC and swim-up effectively
decreased the number of sperms with ultrastructural abnormalities both in the
head and in the tail. However, sperms with ultrastructural abnormalities that
cannot be completely decreased using a combination of DGC and swim-up may impair
fertilization in some cases of intracytoplasmic sperm injection.
PMID- 27616285
TI - Colorimetric stack pad immunoassay for bacterial identification.
AB - A new colorimetric immunoassay concept, utilizing conventional lateral flow
membranes (e.g., conjugation, sample, absorption and nitrocellulose), were placed
in a different configuration in a stacking manner, where the liquid sample that
may contain the analyte diffuses from the bottom to the upper-most layer. The key
element of this proprietary technology is a capture layer, where a nitrocellulose
membrane is modified with the target analyte of interest, namely in this study
target Escherichia coli. During the immunoassay operation, samples contaminated
with the target bacteria will conjugate to their corresponding HRP-antibodies
laying in wait and the immune-target measurand complex flows by capillarity
towards the upper-most layer to generate a colorimetric signal (positive answer)
through an enzymatic reaction. In target-free samples, previously immobilized
target bacteria on the capture layer will prevent the HRP-labeled anti-target
antibodies from migrating to the upper-most layer, where the enzymatic substrate
lays in wait. After optimization, the sensitivity of this approach was found to
be 1,000 folds higher than ELISAs (102cellsmL-1). The advantages of the stacked
pad assay include: miniaturization, operational simplicity, fast response time
(less than 5min), useful sensitivity.
PMID- 27616286
TI - Towards timely Alzheimer diagnosis: A self-powered amperometric biosensor for the
neurotransmitter acetylcholine.
AB - Serious brain disorders, such as the Alzheimer's Disease (AD), are associated
with a marked drop in the levels of important neurotransmitters, such as
acetylcholine (ACh). Real time monitoring of such biomarkers can therefore play a
critical role in enhancing AD therapies by allowing timely diagnosis,
verifications of treatment effectiveness, and developments of new medicines. In
this study, we present the first acetylcholine/oxygen hybrid enzymatic fuel cell
for the self-powered on site detection of ACh in plasma, which is based on the
combination of an enzymatic anode with a Pt cathode. Firstly, an effective
acetylcholinesterase immobilized electrode was developed and its electrochemical
performance evaluated. Highly porous gold was used as the electrode material, and
the enzyme was immobilized via a one step rapid and simple procedure that does
not require the use of harsh chemicals or any electrode/enzyme pre-treatments.
The resulting enzymatic electrode was subsequently used as the anode of a
miniature flow-through membrane-less fuel cell and showed excellent response to
varying concentrations of ACh. The peak power generated by the fuel cell was 4nW
at a voltage of 260mV and with a current density of 9MUAcm-2. The limit of
detection of the fuel cell sensor was 10MUM, with an average response time as
short as 3min. These exciting results open new horizons for point-of-care
Alzheimer diagnosis and provide an attractive potential alternative to
established methods that require laborious and time-consuming sample treatments
and expensive instruments.
PMID- 27616287
TI - Detection of regional DNA methylation using DNA-graphene affinity interactions.
AB - We report a new method for the detection of regional DNA methylation using base
dependent affinity interaction (i.e., adsorption) of DNA with graphene. Due to
the strongest adsorption affinity of guanine bases towards graphene, bisulfite
treated guanine-enriched methylated DNA leads to a larger amount of the adsorbed
DNA on the graphene-modified electrodes in comparison to the adenine-enriched
unmethylated DNA. The level of the methylation is quantified by monitoring the
differential pulse voltammetric current as a function of the adsorbed DNA. The
assay is sensitive to distinguish methylated and unmethylated DNA sequences at
single CpG resolution by differentiating changes in DNA methylation as low as 5%.
Furthermore, this method has been used to detect methylation levels in a
collection of DNA samples taken from oesophageal cancer tissues.
PMID- 27616288
TI - Sonochemical and sustainable synthesis of graphene-gold (G-Au) nanocomposites for
enzymeless and selective electrochemical detection of nitric oxide.
AB - In this study, a sonochemical approach was utilised for the development of
graphene-gold (G-Au) nanocomposite. Through the sonochemical method, simultaneous
exfoliation of graphite and the reduction of gold chloride occurs to produce
highly crystalline G-Au nanocomposite. The in situ growth of gold nanoparticles
(AuNPs) took place on the surface of exfoliated few-layer graphene sheets. The G
Au nanocomposite was characterised by UV-vis, XRD, FTIR, TEM, XPS and Raman
spectroscopy techniques. This G-Au nanocomposite was used to modify glassy carbon
electrode (GCE) to fabricate an electrochemical sensor for the selective
detection of nitric oxide (NO), a critical cancer biomarker. G-Au modified GCE
exhibited an enhanced electrocatalytic response towards the oxidation of NO as
compared to other control electrodes. The electrochemical detection of NO was
investigated by linear sweep voltammetry analysis, utilising the G-Au modified
GCE in a linear range of 10-5000MUM which exhibited a limit of detection of
0.04MUM (S/N=3). Furthermore, this enzyme-free G-Au/GCE exhibited an excellent
selectivity towards NO in the presence of interferences. The synergistic effect
of graphene and AuNPs, which facilitated exceptional electron-transfer processes
between the electrolyte and the GCE thereby improving the sensing performance of
the fabricated G-Au modified electrode with stable and reproducible responses.
This G-Au nanocomposite introduces a new electrode material in the sensitive and
selective detection of NO, a prominent biomarker of cancer.
PMID- 27616290
TI - The effect of regulating molecules on the structure of the PPAR-RXR complex.
AB - The PPAR-RXR complex is one of the most significant and prevalent regulatory
systems, controlling lipid metabolism by gene expression. Both proteins are
members of the nuclear hormone receptor family, consisting of a ligand-binding
domain (LBD), a hinge and a DNA binding domain (DBD). The two proteins form a
heterodimer in the nucleus. The ligand-free complex interacts with corepressor
proteins and blocks the expression of the genes. With the activating ligands and
coactivator segments of regulating proteins, the heterodimer becomes active and
allows translation of the genes under its control. We implemented model
independent all-atom molecular dynamics simulations for clarifying the structure
changes that the activating ligand and the regulatory peptides impose on the PPAR
RXR system, starting with an LBD up to the PPAR-RXR-DNA complex. The simulations
were carried out first with an active state of the protein. Once the relaxed
state was attained, it was transformed into the inactive-state, the resulting
structure was simulated. As the complex alternates between the active-inactive
conformations, most of the changes are noticed at the junction area between the
two subunits, located on the surface of a long fused helical structure made of
H10-H11 of the proteins. The significant differences between the states included
enhanced rigidity of the inactive complex, enhancement of tight contacts. The
main drive for the transformation is the relocation of the tip of H12 of the PPAR
that drives the carboxylate of the C-terminal towards the junction between H10
H11 of the RXR, leading to rearrangement of the main contact zone of the
proteins.
PMID- 27616289
TI - The flexibility and dynamics of protein disulfide isomerase.
AB - We have studied the mobility of the multidomain folding catalyst, protein
disulfide isomerase (PDI), by a coarse-graining approach based on flexibility. We
analyze our simulations of yeast PDI (yPDI) using measures of backbone movement,
relative positions and orientations of domains, and distances between functional
sites. We find that there is interdomain flexibility at every interdomain
junction but these show very different characteristics. The extent of interdomain
flexibility is such that yPDI's two active sites can approach much more closely
than is found in crystal structures-and indeed hinge motion to bring these sites
into proximity is the lowest energy normal mode of motion of the protein. The
flexibility predicted for yPDI (based on one structure) includes the other known
conformation of yPDI and is consistent with (i) the mobility observed
experimentally for mammalian PDI and (ii) molecular dynamics. We also observe
intradomain flexibility and clear differences between the domains in their
propensity for internal motion. Our results suggest that PDI flexibility enables
it to interact with many different partner molecules of widely different sizes
and shapes, and highlights considerable similarities of yPDI and mammalian PDI.
Proteins 2016; 84:1776-1785. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616291
TI - Bone Mass Outcomes in Patients With Osteoporosis Treated With Risedronate After
Alendronate Failure: a 12-Month Follow-Up Study.
AB - Oral bisphosphonates are the drugs most frequently used for the treatment of
osteoporosis. Clinicians usually switch between these drugs in clinical practice
based on differences in efficacy. We aim to investigate the reasons associated
with switching between oral bisphosphonates and to evaluate bone mass response
and the incidence of fractures 12 mo after the exchange in a cohort of patients
with osteoporosis seen at a tertiary hospital. Patients with osteoporosis who
switched between oral bisphosphonates between January 2007 and December 2014 were
included. Bone mass measured by dual-energy X-ray absorptiometry and the
incidence of fracture were evaluated. A total of 112 patients (73.1 yr old on
average, 95.5% women, 98% postmenopausal) were included. All patients were taking
alendronate at the time of the switch to risedronate. In 91 patients (81.3%), the
following reasons for the exchange of medication were identified: bone loss
(59.8%), adverse events (11.6%), and recent fragility fracture (10.7%). One year
after the switch, bone densitometry revealed bone loss in 51 patients (45.5%),
bone mass maintenance in 34 (30.4%), and bone mass gain in 27 (24.1%). No new
vertebral fracture was detected and no nonvertebral fracture was reported in 12
mo of follow-up. Bone mass outcomes (gain, loss, or maintenance) were not
associated with the reason for switching between oral bisphosphonates. Similarly,
none of the parameters evaluated could predict good densitometric response (gain
or maintenance) in this scenario. Our findings suggest that the use of
risedronate should not be recommended in the scenario of treatment failure or
adverse events following the use of alendronate.
PMID- 27616292
TI - Crystal structure of the zinc-bound HhoA protease from Synechocystis sp. PCC
6803.
AB - The high temperature requirement A (HtrA) proteases are oligomeric serine
proteases essential for protein quality control. HtrA homolog A (HhoA) from the
photosynthetic cyanobacterium Synechocystis sp. PCC 6803 assembles into a
proteolytically active hexamer. Herein, we present the crystal structure of the
hexameric HhoA in complex with the copurified peptide. Our data indicate the
presence of three methionines in close proximity to the peptide-binding site of
the PDZ domain. Unexpectedly, we observed that a zinc ion is accommodated within
the central channel formed by a HhoA trimer. However, neither calcium nor
magnesium showed affinity for HhoA. The role of the zinc ion in HhoA was tested
in an in vitro proteolytic assay against the nonspecific substrate beta-casein
and was found to be inhibitory. Our findings provide insights into the regulation
of HhoA by a redox-related mechanism involving methionine residues and by zinc
ion-binding within the central channel.
PMID- 27616295
TI - Investigating investment in biopharmaceutical R&D.
PMID- 27616294
TI - The ever-expanding myokinome: discovery challenges and therapeutic implications.
AB - Exercise reduces the risk of a multitude of disorders, from metabolic disease to
cancer, but the molecular mechanisms mediating the protective effects of exercise
are not completely understood. The realization that skeletal muscle is an
endocrine organ capable of secreting proteins termed 'myokines', which
participate in tissue crosstalk, provided a critical link in the exercise-health
paradigm. However, the myokine field is still emerging, and several challenges
remain in the discovery and validation of myokines. This Review considers these
challenges and highlights some recently identified novel myokines with the
potential to be therapeutically exploited in the treatment of metabolic disease
and cancer.
PMID- 27616296
TI - Mass Spectrometric Analysis of N-Glycoforms of Soybean Allergenic Glycoproteins
Separated by SDS-PAGE.
AB - Glycosylation of many proteins has been revealed to be closely related with food
allergies, and screening and structural analysis of related glycoproteins and
glycoallergens are essential for studies in this field. Herein, we describe
detailed N-glycoform analysis of all glycoprotein fractions of soybean protein
isolate (SPI) separated by sodium dodecyl sulfate polyacrylamide gel
electrophoresis (SDS-PAGE) to disclose structural features of the glycan moieties
of more soybean glycoproteins. SPI was fractionated by SDS-PAGE, and the
generated protein bands were recovered and subjected to in-gel N-glycan release
and labeling using a one-pot method newly developed by our group, followed by
detailed analysis by electrospray ionization mass spectrometry (ESI-MS) and
online hydrophilic interaction liquid chromatography coupled with electrospray
ionization tandem mass spectrometry (HILIC-ESI-MS/MS). As a result, we found
seven bands mainly containing oligomannose-type glycans; two mainly contain core
alpha1,3-fucosylated glycans, and six have no glycans. This study is the first
report that discovers core alpha1,3-fucosylated N-glycans in bands 1, 2, and 6
and discloses bands 3, 4, 5, and 7 as glycoproteins and their N-glycoforms.
Therefore, it can expand our knowledge about soybean protein glycosylation and
provide significant structural reference for research of soybean allergens.
PMID- 27616297
TI - Neogambogic acid prevents silica-induced fibrosis via inhibition of high-mobility
group box 1 and MCP-1-induced protein 1.
AB - BACKGROUND: Silicosis is a systemic disease caused by inhaling silicon dioxide
(SiO2); early stages are characterized by alveolar inflammation, and later stages
are characterized by progressive lung fibrosis. Mounting evidence indicates that
high-mobility group box 1 (HMGB1) is involved in pulmonary fibrosis. Whether
neogambogic acid (NGA) inhibits macrophage and fibroblast activation induced by
SiO2 by targeting HMGB1 remains unclear. METHODS AND RESULTS: Experiments using
cultured mouse macrophages (RAW264.7 cells) demonstrated that SiO2 treatment
induces the expression of HMGB1 in a time- and dose-dependent manner via mitogen
activated protein kinases (MAPKs) and the phosphatidylinositol 3-kinase
(PI3K)/Akt pathway; in turn, this expression causes macrophage apoptosis and
fibroblast activation. Pretreating macrophages with NGA inhibited the HMGB1
expression induced by SiO2 and attenuated both macrophage apoptosis and
fibroblast activation. Moreover, NGA directly inhibited MCP-1-induced protein 1
(MCPIP1) expression, as well as markers of fibroblast activation and migration
induced by SiO2. Furthermore, the effects of NGA on macrophages and fibroblasts
were confirmed in vivo by exposing mice to SiO2. CONCLUSION: NGA can prevent SiO2
induced macrophage activation and apoptosis via HMGB1 inhibition and SiO2-induced
fibrosis via the MCPIP1 pathway. Targeting HMGB1 and MCPIP1 with NGA could
provide insights into the potential development of a therapeutic approach for
alleviating the inflammation and fibrosis induced by SiO2.
PMID- 27616298
TI - Embolization of portosystemic shunts for treatment of medically refractory
hepatic encephalopathy.
PMID- 27616293
TI - Screening out irrelevant cell-based models of disease.
AB - The common and persistent failures to translate promising preclinical drug
candidates into clinical success highlight the limited effectiveness of disease
models currently used in drug discovery. An apparent reluctance to explore and
adopt alternative cell- and tissue-based model systems, coupled with a detachment
from clinical practice during assay validation, contributes to ineffective
translational research. To help address these issues and stimulate debate, here
we propose a set of principles to facilitate the definition and development of
disease-relevant assays, and we discuss new opportunities for exploiting the
latest advances in cell-based assay technologies in drug discovery, including
induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a
chip systems, complemented by advances in single-cell imaging and gene editing
technologies. Funding to support precompetitive, multidisciplinary collaborations
to develop novel preclinical models and cell-based screening technologies could
have a key role in improving their clinical relevance, and ultimately increase
clinical success rates.
PMID- 27616301
TI - Environmental enrichment may protect against neural and behavioural damage caused
by withdrawal from chronic alcohol intake.
AB - Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in
several brain regions, being the medial prefrontal cortex (mPFC) one of the most
affected. These changes presumably reduce the ability of the organism to cope
with these stimuli and may underlie a series of maladaptive behaviours among
which include drug addiction and withdrawal. Drug-addicted individuals show a
pattern of behavior similar to patients with lesions of the mPFC. This impairment
in the decision-making could be one of the mechanisms responsible for the
transition from the casual to compulsive drug use. The environmental enrichment
(EE) has a protective effect on the neural and cognitive impairments induced by
psychoactive drugs, including ethyl alcohol. The present study aims to determine
the influence of withdrawal from intermittent long-term alcohol exposure on
alcohol preference, emotional reactivity and neural aspects of early isolated or
grouped reared rats kept under standard or complex environments and the influence
of social isolation on these measures, as well. Our results point out new
insights on this matter showing that the EE can attenuate the adverse effects of
withdrawal and social isolation on rat's behavior. This effect is probably due to
its protective action on the mPFC integrity, including the cingulate area 1
(Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account
for the absence of changes in the emotional reactivity in EE alcohol withdrawal
rats. We argue that morphological changes at these cortical levels can afford the
emotional, cognitive and behavioural dysregulations verified following withdrawal
from chronic alcohol intake.
PMID- 27616300
TI - Neuroprotective effects of hypothermia in inflammatory-sensitized hypoxic
ischemic encephalopathy.
AB - BACKGROUND: Despite the recent introduction of hypothermia as a mandatory
standard of care, the incidence of neonatal encephalopathy in full-term newborns
and its devastating neuro-behavioral outcomes continues to be a major individual,
familial and social issue. Neonatal encephalopathy is mainly due to the
compounding and interacting effects of hypoxia-ischemia and inflammation
resulting from placental and other perinatal infections. It is unclear why
hypothermia is effective in alleviating neonatal encephalopathy in some, but not
all, full-term newborns. However, newborns exposed to inflammatory-sensitized
hypoxia-ischemia seem to have less therapeutic benefit from hypothermia than
those exposed to hypoxia-ischemia alone. OBJECTIVES: To clarify this uncertainty,
we tested the efficacy of hypothermia in a double-hit model of neonatal
encephalopathy induced by inflammatory-sensitized hypoxia-ischemia. METHODS:
Using a rat preclinical model of endotoxin plus hypoxia-ischemia-induced neonatal
encephalopathy of term newborns, we assessed the following in pups exposed (or
not) to hypothermia: the extent of brain injuries and the expressions of
molecules implicated in neural cell death, namely: pro-inflammatory cytokines,
matrix metalloproteinase-9, antioxidant enzymes, as well as receptor-interacting
protein-3. RESULTS: Hypothermia was neuroprotective on inflammatory-sensitized
hypoxia-ischemia-induced penumbra, but not core, brain injuries. This beneficial
effect was associated with a hypothermia-induced increase of antioxidant enzymes
(superoxide dismutase-1, glutathione peroxidase-1), but was not associated with
any variations of the other inflammatory mediators tested, namely: interleukin
1beta, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and matrix
metalloproteinase-9. CONCLUSION: Hypothermia is neuroprotective against
inflammatory-sensitized hypoxia-ischemia possibly through a hypothermia-induced
increase of antioxidant enzymes. This neuroprotective effect seems to be
independent of the interleukin-1 system.
PMID- 27616302
TI - Sex and intrauterine growth restriction modify brain neurotransmitters profile of
newborn piglets.
AB - The current study aimed to determine, using a swine model of intrauterine growth
restriction (IUGR), whether short- and long-term neurological deficiencies and
interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to
altered pattern of neurotransmitters. Hence, we compared the quantities of
different neurotransmitters (catecholamines and indoleamines), which were
determined by HPLC, at brain structures related to the limbic system (hippocampus
and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The
results showed, firstly, significant effects of sex on the NBW newborns, with
females having higher dopamine (DA) concentrations than males. The IUGR processes
affected DA metabolism, with LBW piglets having lower concentrations of
noradrenaline at the hippocampus and higher concentrations of the DA metabolites,
homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW
neonates. The effects of IUGR were modulated by sex; there were no significant
differences between LBW and NBW females, but LBW males had higher HVA
concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic
acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion,
the present study shows that IUGR is mainly related to changes, modulated by sex,
in the concentrations of catecholamine neurotransmitters, which are related to
adaptation to physical activity and to essential cognitive functions such as
learning, memory, reward-motivated behavior and stress.
PMID- 27616303
TI - Grip force and force sharing in two different manipulation tasks with bottles.
AB - Grip force and force sharing during two activities of daily living were analysed
experimentally in 10 right-handed subjects. Four different bottles, filled to two
different levels, were manipulated for two tasks: transporting and pouring. Each
test subject's hand was instrumented with eight thin wearable force sensors. The
grip force and force sharing were significantly different for each bottle model.
Increasing the filling level resulted in an increase in grip force, but the ratio
of grip force to load force was higher for lighter loads. The task influenced the
force sharing but not the mean grip force. The contributions of the thumb and
ring finger were higher in the pouring task, whereas the contributions of the
palm and the index finger were higher in the transport task. Mean force sharing
among fingers was 30% for index, 29% for middle, 22% for ring and 19% for little
finger. Practitioner Summary: We analysed grip force and force sharing in two
manipulation tasks with bottles: transporting and pouring. The objective was to
understand the effects of the bottle features, filling level and task on the
contribution of different areas of the hand to the grip force. Force sharing was
different for each task and the bottles features affected to both grip force and
force sharing.
PMID- 27616299
TI - Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D
Culture into Hepatocyte-like Cells through Direct Wnt/beta-catenin Pathway
Inhibition.
AB - Treatment of acute liver failure by cell transplantation is hindered by a
shortage of human hepatocytes. Current protocols for hepatic differentiation of
human induced pluripotent stem cells (hiPSCs) result in low yields, cellular
heterogeneity, and limited scalability. In the present study, we have developed a
novel multicellular spheroid-based hepatic differentiation protocol starting from
embryoid bodies of hiPSCs (hiPSC-EBs) for robust mass production of human
hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway. The
resultant hiPSC-EB-HLCs expressed liver-specific genes, secreted hepatic proteins
such as Albumin, Alpha Fetoprotein, and Fibrinogen, metabolized ammonia, and
displayed cytochrome P450 activities and functional activities typical of mature
primary hepatocytes, such as LDL storage and uptake, ICG uptake and release, and
glycogen storage. Cell transplantation of hiPSC-EB-HLC in a rat model of acute
liver failure significantly prolonged the mean survival time and resolved the
liver injury when compared to the no-transplantation control animals. The
transplanted hiPSC-EB-HLCs secreted human albumin into the host plasma throughout
the examination period (2 weeks). Transplantation successfully bridged the
animals through the critical period for survival after acute liver failure,
providing promising clues of integration and full in vivo functionality of these
cells after treatment with WIF-1 and DKK-1.
PMID- 27616304
TI - TLR2 promotes human intrahepatic cholangiocarcinoma cell migration and invasion
by modulating NF-kappaB pathway-mediated inflammatory responses.
AB - Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive malignancy that is
often diagnosed at advanced stages, which limits treatment options. Despite its
increasing incidence and mortality worldwide, the pathogenesis of ICC is not well
understood. Here, we examined the effect of the dysregulation of innate immune
responses on carcinogenesis by investigating the role of toll-like receptor
(TLR)2 in the pathogenesis and invasiveness of ICC and explored the underlying
mechanisms. Immunohistochemical analysis, real-time PCR, and western blotting
showed higher TLR2 levels in ICC tissues and cell lines. Silencing and
overexpression experiments indicated that TLR2 promotes ICC migration and
invasion, induces the expression of epithelial-to-mesenchymal transition (EMT)
markers, and upregulates the proinflammatory cytokines tumor necrosis factor
(TNF)-alpha, interleukin (IL)-6, and IL-1beta concomitant with the activation of
NF-kappaB signaling. Inhibition of NF-kappaB activity abolished the effect of
TLR2 on EMT, invasion and migration, and the TLR2-induced upregulation of
proinflammatory cytokines, and suppressed the effect of exogenous TNF-alpha and
IL-6 on restoring EMT, migration and invasion in the presence of TLR2. Taken
together, our results indicate that TLR2 has protumorigenic and prometastatic
effects in ICC through the upregulation of inflammatory cytokines induced by the
activation of NF-kappaB signaling, suggesting potential novel therapeutic targets
for the treatment of ICC.
PMID- 27616307
TI - 'It's a very complicated issue here': understanding the limited and declining use
of manual vacuum aspiration for postabortion care in Malawi: a qualitative study.
AB - Malawi has one of the highest maternal mortality ratios in the world. Unsafe
abortions are an important contributor to Malawi's maternal mortality and
morbidity, where abortion is illegal except to save the woman's life.
Postabortion care (PAC) aims to reduce adverse consequences of unsafe abortions,
in part by treating incomplete abortions. Although global and national PAC
policies recommend manual vacuum aspiration (MVA) for treatment of incomplete
abortion, usage in Malawi is low and appears to be decreasing, with sharp
curettage being used in preference. There is limited evidence regarding what
influences rejection of recommended PAC innovations. Hence, drawing on Greenhalgh
et al. 's (2004. Diffusion of innovations in service organizations: systematic
review and recommendations. Milbank Quarterly 82: 581-629.) diffusion of
healthcare innovation framework, this qualitative study aimed to investigate
factors contributing to the limited and declining use of MVA in Malawi. Semi
structured interviews with 17 PAC providers in a central hospital and a district
hospital indicate that a range of factors coalesce and influence PAC and MVA use
in Malawi. Factors pertain to four main domains: the system (shortages of
material and human resources; lack of training, supervision and feedback),
relationships (power dynamics; expected job roles), the health workers (attitudes
towards abortion and PAC; prioritization of PAC) and the innovation (perceived
risks and benefits of MVA use). Effective and sustainable PAC policy must adopt a
broader people-centred health systems approach which considers all these factors,
their interactions and the wider socio-cultural, legal and political context of
abortion and PAC. The study showed the value of using Greenhalgh et al. 's (2004.
Diffusion of innovations in service organizations: systematic review and
recommendations. Milbank Quarterly 82: 581-629.) framework to consider the
complex interaction of factors surrounding innovation use (or lack of), but
provided more insights into rejections of innovations and, particularly, a low-
and middle-income country perspective.
PMID- 27616309
TI - Letter From the Guest Editor: Spinal Cord Imaging. I: Anatomical,
Pathophysiologic, and Clinical Correlate.
PMID- 27616308
TI - Blissfully Blind or Painfully Aware? Exploring the Beliefs People With
Interpersonal Problems Have About Their Reputation.
AB - OBJECTIVE: Problematic interpersonal behavior might stem from and be maintained
by the beliefs people have about how others see them (i.e., metaperceptions). The
current study tested whether people with interpersonal problems formed more or
less accurate metaperceptions about their personality (meta-accuracy), whether
they thought others saw them in more or less positive ways (positivity), and
whether they underestimated or overestimated how much others saw them as they saw
themselves (transparency). METHOD: Participants (NTime1 = 189; NTime2 = 175;
Mage = 19.78; 36% male) completed a measure of interpersonal problems and
provided personality judgments and metaperceptions for a group of peers after a
first impression and after 4 months of acquaintanceship. RESULTS: Generalized
distress was associated with less positive metaperceptions at both times and with
higher meta-accuracy after 4 months. Dominance problems were not associated with
meta-accuracy, positivity, or transparency after a first impression, but
dominance was linked to lower meta-accuracy and lower positivity after 4 months.
Affiliation problems were associated with higher meta-accuracy after a first
impression and with higher positivity and transparency at both times.
CONCLUSIONS: Metaperceptions were linked to interpersonal problems, and these
expectations might partially explain some maladaptive patterns of behavior.
PMID- 27616310
TI - Spinal Cord Anatomy and Clinical Syndromes.
AB - We review the anatomy of the spinal cord, providing correlation with key
functional and clinically relevant neural pathways, as well as magnetic resonance
imaging. Peripherally, the main descending (corticospinal tract) and ascending
(gracilis or cuneatus fasciculi and spinothalamic tracts) pathways compose the
white matter. Centrally, the gray matter can be divided into multiple laminae.
Laminae 1-5 carry sensitive neuron information in the posterior horn, and lamina
9 carries most lower motor neuron information in the anterior horn. Damage to the
unilateral corticospinal tract (upper motor neuron information) or gracillis
cuneatus fasciculi (touch and vibration) correlates with ipsilateral clinical
findings, whereas damage to unilateral spinothalamic tract (pain-temperature)
correlates with contralateral clinical findings. Damage to commissural fibers
correlates with a suspended bilateral "girdle" sensory level. Autonomic
dysfunction is expected when there is bilateral cord involvement.
PMID- 27616311
TI - Abnormal Spinal Cord Magnetic Resonance Signal: Approach to the Differential
Diagnosis.
AB - T2-hyperintense signal abnormalities within the spinal cord on magnetic resonance
imaging can evoke a broad differential diagnosis and can present a diagnostic
dilemma. Here, we review and provide a succinct and relevant differential
diagnosis based on imaging patterns and anatomical or physiopathologic
correlation. Clues and imaging pearls are provided focusing on inflammatory,
infectious, demyelinating, vascular, and metabolic involvement of the spinal
cord.
PMID- 27616313
TI - Spinal Cord in Multiple Sclerosis: Magnetic Resonance Imaging Features and
Differential Diagnosis.
AB - Multiple sclerosis (MS) is an idiopathic inflammatory disorder of the central
nervous system that affects not only the brain but also the spinal cord. In the
diagnostic and monitoring process of MS, spinal cord magnetic resonance imaging
(MRI) is not performed as commonly as brain MRI, mainly because of certain
technical difficulties and the increase in total acquisition time. Nonetheless,
spinal cord MRI findings are important to establish a prompt accurate diagnosis
of MS, impart prognostic information, and provide valuable data for monitoring
the disease course in certain cases. In this article, we discuss the technical
aspects of spinal cord MRI, the typical MRI features of the spinal cord in MS,
the clinical indications for this examination, and the differential diagnosis
with other disorders that may produce similar clinical or MRI findings.
PMID- 27616312
TI - Transverse Myelitis and Neuromyelitis Optica Spectrum Disorders.
AB - Transverse myelitis is defined as inflammation of the spinal cord, named because
of its typical clinical presentation with bandlike symptoms of altered sensation
or pain in a horizontal fashion-at a specific dermatome level. Radiographic
patterns might vary but the idiopathic form is more frequent to present as
involvement of 3-4 vertebral segments and both sides of the cord. It is now
recognized that there are numerous other causes as well as the idiopathic type,
with often atypical features and geographic variation. There is also increasing
recognition of other forms of myelitis, particularly the longitudinally extensive
manifestation with involvement of 3 or more vertebral segments. Neuromyelitis
optica, one of these subtypes can be diagnosed by means of an antibody
assessment. The picture is more complicated with the expansion of the description
to involve neuromyelitis optica spectrum disorders, new antibodies such as myelin
oligodendrocyte glycoprotein and the inclusion of an antibody-negative variant.
This article describes the different entities of transverse myelitis, with a
particular focus on neuromyelitis optica spectrum disorders.
PMID- 27616314
TI - An Imaging-Based Approach to Spinal Cord Infection.
AB - Infections of the spinal cord, nerve roots, and surrounding meninges are
uncommon, but highly significant given their potential for severe morbidity and
even mortality. Prompt diagnosis can be lifesaving, as many spinal infections are
treatable. Advances in imaging technology have now firmly established magnetic
resonance imaging (MRI) as the gold standard for spinal cord imaging evaluation,
enabling the depiction of infectious myelopathies with exquisite detail and
contrast. In this article, we aim to provide an overview of MRI findings for
spinal cord infections with special focus on imaging patterns of infection that
are primarily confined to the spinal cord, spinal meninges, and spinal nerve
roots. In this context, we describe and organize this review around 5 distinct
patterns of transverse spinal abnormality that may be detected with MRI as
follows: (1) extramedullary, (2) centromedullary, (3) eccentric, (4) frontal
horn, and (5) irregular. We seek to classify the most common presentations for a
wide variety of infectious agents within this image-based framework while
realizing that significant overlap and variation exists, including some
infections that remain occult with conventional imaging techniques.
PMID- 27616315
TI - Imaging of Spinal Cord Injury: Acute Cervical Spinal Cord Injury, Cervical
Spondylotic Myelopathy, and Cord Herniation.
AB - We review the pathophysiology and imaging findings of acute traumatic spinal cord
injury (SCI), cervical spondylotic myelopathy, and briefly review the much less
common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is
devastating to the patient and the costs to society are staggering. There are
currently no "cures" for SCI and the only accepted pharmacologic treatment
regimen for traumatic SCI is currently being questioned. Evaluation and
prognostication of SCI is a demanding area with significant deficiencies,
including lack of biomarkers. Accurate classification of SCI is heavily dependent
on a good clinical examination, the results of which can vary substantially based
upon the patient's condition or comorbidities and the skills of the examiner.
Moreover, the full extent of a patients' neurologic injury may not become
apparent for days after injury; by then, therapeutic response may be limited.
Although magnetic resonance imaging (MRI) is the best imaging modality for the
evaluation of spinal cord parenchyma, conventional MR techniques do not appear to
differentiate edema from axonal injury. Recently, it is proposed that in addition
to characterizing the anatomic extent of injury, metrics derived from
conventional MRI and diffusion tensor imaging, in conjunction with the
neurological examination, can serve as a reliable objective biomarker for
determination of the extent of neurologic injury and early identification of
patients who would benefit from treatment. Cervical spondylosis is a common
disorder affecting predominantly the elderly with a potential to narrow the
spinal canal and thereby impinge or compress upon the neural elements leading to
cervical spondylotic myelopathy and radiculopathy. It is the commonest
nontraumatic cause of spinal cord disorder in adults. Imaging plays an important
role in grading the severity of spondylosis and detecting cord abnormalities
suggesting myelopathy.
PMID- 27616316
TI - Toxic and Metabolic Myelopathies.
AB - Myelopathy describes any neurologic deficit related to the spinal cord. It is
most commonly caused by its compression by neoplasms, degenerative disc disease,
trauma, or infection. Less common causes of myelopathy include spinal cord
tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and
metabolic disorders. Conditions affecting the spinal cord must be recognized as
early as possible to prevent progression that may lead to permanent disability.
Biopsy is rarely performed, thus the diagnosis and management rely on patient's
history, physical examination, laboratory results, and imaging findings. Here we
review the clinical presentations, pathophysiological mechanisms, and magnetic
resonance imaging findings of myelopathies related to metabolic or toxic
etiologies.
PMID- 27616317
TI - Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous
Congestive Myelopathy.
AB - Vascular pathologies of the spinal cord are rare and often overlooked. This
article presents clinical and imaging approaches to the diagnosis and management
of spinal vascular conditions most commonly encountered in clinical practice.
Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the
spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical
classification schemes, clinical presentations, imaging findings, and treatment
modalities are considered. Recent advances in genetic and syndromic vascular
pathologies of the spinal cord are also discussed. Clinically relevant spinal
vascular anatomy is reviewed in detail.
PMID- 27616318
TI - Neoplastic and Paraneoplastic Involvement of the Spinal Cord.
AB - Neoplasia of the spinal cord, including both primary and metastatic tumors, is
relatively rare, representing 4%-10% of all central nervous system tumors, and
can present a diagnostic challenge to the radiologist. More than 90% of primary
spinal cord neoplasms are derived from the glial cell lineage, including the 2
most common tumors ependymoma and astrocytoma. However, less common spinal cord
tumors, including metastatic disease, as well as nonneoplastic and paraneoplastic
processes should be considered in the diagnosis of intramedullary spinal cord
lesions.
PMID- 27616319
TI - Enhancing Neurosurgical Education in Low- and Middle-income Countries: Current
Methods and New Advances.
AB - Low- and middle-income countries (LMICs) face a critical shortage of basic
surgical services. Adequate neurosurgical services can have a far-reaching
positive impact on society's health care and, consequently, the economic
development in LMICs. Yet surgery, and specifically neurosurgery has been a long
neglected sector of global health. This article reviews the current efforts to
enhance neurosurgery education in LMICs and outlines ongoing approaches for
improvement. In addition, we introduce the concept of a sustainable and cost
effective model to enhance neurosurgical resources in LMICs and describe the
process and methods of online curriculum development.
PMID- 27616320
TI - Interactive Bio-feedback Therapy Using Hybrid Assistive Limbs for Motor Recovery
after Stroke: Current Practice and Future Perspectives.
AB - Interactive bio-feedback (iBF) was initially developed for the rehabilitation of
motor function in patients with neurological disorders, and subsequently yielded
the development of the hybrid assistive limb (HAL). Here, we provide a review of
the theory underlying HAL treatment as well as our clinical experience and
recommendations for future clinical studies using HAL in acute stroke patients.
We performed a PubMed-based literature search, a retrospective data review of our
acute stroke case series, and included a sample case report of our findings.
Given past animal studies and functional imaging results, iBF therapy using the
HAL in the acute phase of stroke seems an appropriate approach for preventing
learned non-use and interhemispheric excitation imbalances. iBF therapy may
furthermore promote appropriate neuronal network reorganization. Based on
experiences in our stroke center, HAL rehabilitation is a safe and effective
treatment modality for recovering motor impairments after acute stroke, and
allows the design of tailored rehabilitation programs for individual patients.
iBF therapy through the HAL system seems to be an effective and promising
approach to stroke rehabilitation; however, the superiority of this treatment to
conventional rehabilitation remains unclear. Further clinical studies are
warranted. Additionally, the formation of a patient registry will permit a meta
analysis of HAL cases and address the problems associated with a controlled trial
(e.g., the heterogeneity of an acute stroke cohort). The development of robotic
engineering will improve the efficacy of HAL rehabilitation and has the potential
to standardize patient rehabilitation practice.
PMID- 27616321
TI - An 11-year experience of acquired von Willebrand syndrome in children diagnosed
with Wilms tumour in a tertiary referral centre.
AB - Wilms tumour (WT) is the commonest primary malignant renal tumour of childhood.
Acquired von Willebrand syndrome (avWS) is a well-described paraneoplastic
phenomenon, but it is uncommon and may not be detected until clinically
significant bleeding is encountered during interventional procedures. Previous
studies on small cohorts of patients have determined an incidence of between 4
and 8%. We have performed a retrospective study on cases of WT presenting over an
11.5-year period to a paediatric haematology/oncology unit in a tertiary referral
centre to review the incidence of avWS, bleeding phenotype, management, and
response to treatment of the primary pathology.
PMID- 27616323
TI - Species Distributions, Quantum Theory, and the Enhancement of Biodiversity
Measures.
AB - Species distributions are typically represented by records of their observed
occurrence at a given spatial and temporal scale. Such records are inevitably
incomplete and contingent on the spatial-temporal circumstances under which the
observations were made. Moreover, organisms may respond differently to similar
environmental conditions at different places or moments, so their distribution
is, in principle, not completely predictable. We argue that this uncertainty
exists, and warrants considering species distributions as analogous to coherent
quantum objects, whose distributions are better described by a wavefunction
rather than by a set of locations. We use this to extend the existing concept of
"dark diversity", which incorporates into biodiversity metrics those species that
could, but which have not yet been observed to, inhabit a region-thereby
developing the idea of "potential biodiversity". We show how conceptualizing
species' distributions in this way could help overcome important weaknesses in
current biodiversity metrics, both in theory and by using a worked case study of
mammal distributions in Spain over the last decade. We propose that considerable
theoretical advances could eventually be gained through interdisciplinary
collaboration between biogeographers and quantum physicists. [Biogeography;
favorability; physics; predictability; probability; species occurrence;
uncertainty; wavefunction.
PMID- 27616322
TI - Sodium nitrite exerts an antihypertensive effect and improves endothelial
function through activation of eNOS in the SHR.
AB - Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an
endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present
study was designed to investigate the effect of chronic NaNO2 administration on
arterial systolic blood pressure (SBP) and vascular function in hypertensive
rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to
spontaneously (SHR) and Nomega-Nitro-L-arginine methyl ester hydrochloride (L
NAME) treated hypertensive SD rats. Arterial SBP and vascular function in
isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic
guanosine monophosphate (cGMP) levels were measured using commercially available
assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM
fluorescence while the proteins involved in endothelial nitric oxide synthase
(eNOS) activation was determined by Western blotting. NaNO2 treatment reduced
SBP, improved the impaired endothelium-dependent relaxation, increased plasma
total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR.
Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in
NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in
L-NAME treated hypertensive SD rats. The present study provides evidence that
chronic treatment of genetically hypertensive rats with NaNO2 improves
endothelium-dependent relaxation in addition to its antihypertensive effect,
partly through mechanisms involving activation of eNOS.
PMID- 27616325
TI - Trans-nonachlor decreases miR-141-3p levels in human melanocytes in vitro
promoting melanoma cell characteristics and shows a multigenerational impact on
miR-8 levels in Drosophila.
AB - Epidemiological association studies have revealed a role for pesticides in cancer
occurrence, while a growing number of reports have highlighted the deleterious
epigenetic modifications that can be produced by environmental factors. However,
epidemiological data currently lack molecular support to unravel the epigenetic
impact of pesticides on carcinogenesis. Based on epidemiological studies of
melanoma, our data show for the first time that trans-nonachlor (TNC), a
component of the pesticide chlordane, modulates the microRNA miR-141-3p in human
melanocytic cells in vitro, with effects on melanomagenesis parameters. TNC
downregulates the level of miR-141-3p in normal melanocytes to levels found
endogenously in several melanoma cell lines. Ectopic expression of either a
synthetic miRNA mimic or inhibitor in human melanocytic cells revealed that TNC
counteracts the inhibitory effects of miR-141-3p on melanoma cell anchorage
independent growth ability, their invasive potential, and expression of a
multipotent, embryonic-like, aggressive cancer phenotype (termed vasculogenic
mimicry), involving VE-Cadherin. In addition, the data suggest that miR-141-3p
regulates vasculogenic mimicry through extracellular signal-regulated kinase 1/2
(ERK1/2) and phosphatidyl inositol-3-kinase (PI3K). Notably, in the Drosophila
animal model, TNC also decreased the level of miR-8, the sole miR-141-3p fly
ortholog. Importantly, the downregulation of miR-8 levels induced by TNC in
ancestors was transmitted through multigenerations, with a progressive reversion
over time. Such a decrease in miR-8 levels translated to a loss-of-weight
phenotype in offspring. Providing support to epidemiological data, these results
altogether suggest that TNC may favor melanomagenesis by lowering the levels of
miR-141-3p, thereby activating melanoma cell processes. Although any such
conclusions in humans are yet to be determined, these experiments in Drosophila
demonstrate that TNC can promote an epigenetic multigenerational inheritance of
the miR-141-3p/miR-8 defect. This study therefore justifies the development of
molecular investigations to decipher the toxic epigenetic heritable impact of
pesticides on cancer occurrence.
PMID- 27616324
TI - Toward a Self-Updating Platform for Estimating Rates of Speciation and Migration,
Ages, and Relationships of Taxa.
AB - Rapidly growing biological data-including molecular sequences and fossils-hold an
unprecedented potential to reveal how evolutionary processes generate and
maintain biodiversity. However, researchers often have to develop their own
idiosyncratic workflows to integrate and analyze these data for reconstructing
time-calibrated phylogenies. In addition, divergence times estimated under
different methods and assumptions, and based on data of various quality and
reliability, should not be combined without proper correction. Here we introduce
a modular framework termed SUPERSMART (Self-Updating Platform for Estimating
Rates of Speciation and Migration, Ages, and Relationships of Taxa), and provide
a proof of concept for dealing with the moving targets of evolutionary and
biogeographical research. This framework assembles comprehensive data sets of
molecular and fossil data for any taxa and infers dated phylogenies using robust
species tree methods, also allowing for the inclusion of genomic data produced
through next-generation sequencing techniques. We exemplify the application of
our method by presenting phylogenetic and dating analyses for the mammal order
Primates and for the plant family Arecaceae (palms). We believe that this
framework will provide a valuable tool for a wide range of hypothesis-driven
research questions in systematics, biogeography, and evolution. SUPERSMART will
also accelerate the inference of a "Dated Tree of Life" where all node ages are
directly comparable. [Bayesian phylogenetics; data mining; divide-and-conquer
methods; GenBank; multilocus multispecies coalescent; next-generation sequencing;
palms; primates; tree calibration.].
PMID- 27616326
TI - The Role of Climate Covariability on Crop Yields in the Conterminous United
States.
AB - The covariability of temperature (T), precipitation (P) and radiation (R) is an
important aspect in understanding the climate influence on crop yields. Here, we
analyze county-level corn and soybean yields and observed climate for the period
1983-2012 to understand how growing-season (June, July and August) mean T, P and
R influence crop yields jointly and in isolation across the CONterminous United
States (CONUS). Results show that nationally averaged corn and soybean yields
exhibit large interannual variability of 21% and 22%, of which 35% and 32% can be
significantly explained by T and P, respectively. By including R, an additional
of 5% in variability can be explained for both crops. Using partial regression
analyses, we find that studies that ignore the covariability among T, P, and R
can substantially overestimate the sensitivity of crop yields to a single climate
factor at the county scale. Further analyses indicate large spatial variation in
the relative contributions of different climate variables to the variability of
historical corn and soybean yields. The structure of the dominant climate factors
did not change substantially over 1983-2012, confirming the robustness of the
findings, which have important implications for crop yield prediction and crop
model validations.
PMID- 27616327
TI - Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow
Specificity CphA Metallo-beta-Lactamase is Fragile to Mutations.
AB - CphA is a Zn(2+)-dependent metallo-beta-lactamase that efficiently hydrolyzes
only carbapenem antibiotics. To understand the sequence requirements for CphA
function, single codon random mutant libraries were constructed for residues in
and near the active site and mutants were selected for E. coli growth on
increasing concentrations of imipenem, a carbapenem antibiotic. At high
concentrations of imipenem that select for phenotypically wild-type mutants, the
active-site residues exhibit stringent sequence requirements in that nearly all
residues in positions that contact zinc, the substrate, or the catalytic water do
not tolerate amino acid substitutions. In addition, at high imipenem
concentrations a number of residues that do not directly contact zinc or
substrate are also essential and do not tolerate substitutions. Biochemical
analysis confirmed that amino acid substitutions at essential positions decreased
the stability or catalytic activity of the CphA enzyme. Therefore, the CphA
active - site is fragile to substitutions, suggesting active-site residues are
optimized for imipenem hydrolysis. These results also suggest that resistance to
inhibitors targeted to the CphA active site would be slow to develop because of
the strong sequence constraints on function.
PMID- 27616328
TI - The fitness burden imposed by synthesising quorum sensing signals.
AB - It is now well established that bacterial populations utilize cell-to-cell
signaling (quorum-sensing, QS) to control the production of public goods and
other co-operative behaviours. Evolutionary theory predicts that both the cost of
signal production and the response to signals should incur fitness costs for
producing cells. Although costs imposed by the downstream consequences of QS have
been shown, the cost of QS signal molecule (QSSM) production and its impact on
fitness has not been examined. We measured the fitness cost to cells of
synthesising QSSMs by quantifying metabolite levels in the presence of QSSM
synthases. We found that: (i) bacteria making certain QSSMs have a growth defect
that exerts an evolutionary cost, (ii) production of QSSMs negatively correlates
with intracellular concentrations of QSSM precursors, (iii) the production of
heterologous QSSMs negatively impacts the production of a native QSSM that shares
common substrates, and (iv) supplementation with exogenously added metabolites
partially rescued growth defects imposed by QSSM synthesis. These data identify
the sources of the fitness costs incurred by QSSM producer cells, and indicate
that there may be metabolic trade-offs associated with QS signaling that could
exert selection on how signaling evolves.
PMID- 27616329
TI - Antagonizing effect of CLPABP on the function of HuR as a regulator of ARE
containing leptin mRNA stability and the effect of its depletion on obesity in
old male mouse.
AB - Cardiolipin and phosphatidic acid-binding protein (CLPABP) is a pleckstrin
homology domain-containing protein and is localized on the surface of
mitochondria of cultured cells as a large protein-RNA complex. To analyze the
physiological functions of CLPABP, we established and characterized a CLPABP
knockout (KO) mouse. Although expression levels of CLPABP transcripts in the
developmental organs were high, CLPABP KO mice were normal at birth and grew
normally when young. However, old male mice presented a fatty phenotype, similar
to that seen in metabolic syndrome, in parallel with elevated male- and age
dependent CLPABP gene expression. One of the reasons for this obesity in CLPABP
KO mice is dependence on increases in leptin concentration in plasma. The leptin
transcripts were also upregulated in the adipose tissue of KO mice compared with
wild-type (WT) mice. To understand the difference in levels of the
transcriptional product, we focused on the effect of CLPABP on the stability of
mRNA involving an AU-rich element (ARE) in its 3'UTR dependence on the RNA
stabilizer, human antigen R (HuR), which is one of the CLPABP-binding proteins.
Increase in stability of ARE-containing mRNAs of leptin by HuR was antagonized by
the expression of CLPABP in cultured cells. Depletion of CLPABP disturbed the
normal subcellular localization of HuR to stress granules, and overexpression of
CLPABP induced instability of leptin mRNA by inhibiting HuR function.
Consequently, leptin levels in old male mice might be regulated by CLPABP
expression, which might lead to body weight control.
PMID- 27616330
TI - Upregulation of the S1P3 receptor in metastatic breast cancer cells increases
migration and invasion by induction of PGE2 and EP2/EP4 activation.
AB - Breast cancer is one of the most common and devastating malignancies among women
worldwide. Recent evidence suggests that malignant progression is also driven by
processes involving the sphingolipid molecule sphingosine 1-phosphate (S1P) and
its binding to cognate receptor subtypes on the cell surface. To investigate the
effect of this interaction on the metastatic phenotype, we used the breast cancer
cell line MDA-MB-231 and the sublines 4175 and 1833 derived from lung and bone
metastases in nude mice, respectively. In both metastatic cell lines expression
of the S1P3 receptor was strongly upregulated compared to the parental cells and
correlated with higher S1P-induced intracellular calcium ([Ca2+]i), higher
cyclooxygenase (COX)-2 and microsomal prostaglandin (PG) E2 synthase expression,
and consequently with increased PGE2 synthesis. PGE2 synthesis was decreased by
antagonists and siRNA against S1P3 and S1P2. Moreover, in parental MDA-MB-231
cells overexpression of S1P3 by cDNA transfection also increased PGE2 synthesis,
but only after treatment with the DNA methyltransferase inhibitor 5-aza-2
deoxycytidine, indicating reversible silencing of the COX-2 promoter.
Functionally, the metastatic sublines showed enhanced migration and Matrigel
invasion in adapted Boyden chamber assays, which further increased by S1P
stimulation. This response was abrogated by either S1P3 antagonism, COX-2
inhibition or PGE2 receptor 2 (EP2) and 4 (EP4) antagonism, but not by S1P2
antagonism. Our data demonstrate that in breast cancer cells overexpression of
S1P3 and its activation by S1P has pro-inflammatory and pro-metastatic potential
by inducing COX-2 expression and PGE2 signaling via EP2 and EP4.
PMID- 27616331
TI - Postoperative analgesia with dexmedetomidine in interscalene block. Comparative
study.
AB - INTRODUCTION: Dexmedetomidine prolongs sensory block of ropivacaine. Our
objective was to study whether this extension would produce better postoperative
pain control compared to that produced by clonidine in patients undergoing
arthroscopic shoulder. MATERIALS AND METHODS: Study comparative, longitudinal,
controlled, randomized into 3 groups. Control group I: ropivacaine 0.75%
clonidine group II: 0.75% ropivacaine plus clonidine 1mg/kg group
iiidexmedetomidine: 0.75% ropivacaine more dexmedetomidine 1mg/kg. Interscalene
block single dose ultrasound-guided. Sensory and motor blockade, pain intensity,
sedation level, heart rate, respiratory rate, blood pressure at 6, 12 and 24hours
was measured. RESULTS: Pain intensity at 6hours in groups I and II moderate to
severe pain, mild pain group iii. At 12hours the groups IIand II showed moderate
to severe pain by more than 60% of patients, and in group iiionly 10%. At 24hours
I and II group 20% of patients they continued to moderate pain. CONCLUSION: The
prolonged interscalene block produced by dexmedetomidine provided better
postoperative pain control during the first 24hours.
PMID- 27616332
TI - Quantifying evolutionary dynamics from variant-frequency time series.
AB - From Kimura's neutral theory of protein evolution to Hubbell's neutral theory of
biodiversity, quantifying the relative importance of neutrality versus selection
has long been a basic question in evolutionary biology and ecology. With deep
sequencing technologies, this question is taking on a new form: given a time
series of the frequency of different variants in a population, what is the
likelihood that the observation has arisen due to selection or neutrality? To
tackle the 2-variant case, we exploit Fisher's angular transformation, which
despite being discovered by Ronald Fisher a century ago, has remained an
intellectual curiosity. We show together with a heuristic approach it provides a
simple solution for the transition probability density at short times, including
drift, selection and mutation. Our results show under that under strong selection
and sufficiently frequent sampling these evolutionary parameters can be
accurately determined from simulation data and so they provide a theoretical
basis for techniques to detect selection from variant or polymorphism frequency
time-series.
PMID- 27616334
TI - Obesity paradox in cirrhosis: is it real or just an illusion?
PMID- 27616333
TI - Copper Ion Binding Site in beta-Amyloid Peptide.
AB - beta-Amyloid aggregates in the brain play critical roles in Alzheimer's disease,
a chronic neurodegenerative condition. Amyloid-associated metal ions,
particularly zinc and copper ions, have been implicated in disease pathogenesis.
Despite the importance of such ions, the binding sites on the beta-amyloid
peptide remain poorly understood. In this study, we use scanning tunneling
microscopy, circular dichroism, and surface-enhanced Raman spectroscopy to probe
the interactions between Cu2+ ions and a key beta-amyloid peptide fragment,
consisting of the first 16 amino acids, and define the copper-peptide binding
site. We observe that in the presence of Cu2+, this peptide fragment forms beta
sheets, not seen without the metal ion. By imaging with scanning tunneling
microscopy, we are able to identify the binding site, which involves two
histidine residues, His13 and His14. We conclude that the binding of copper to
these residues creates an interstrand histidine brace, which enables the
formation of beta-sheets.
PMID- 27616335
TI - Hepatitis C - the brain strain.
PMID- 27616336
TI - Intramolecular Oxidative O-Demethylation of an Oxoferryl Porphyrin Complexed with
a Per-O-methylated beta-Cyclodextrin Dimer.
AB - The intramolecular oxidation of ROCH3 to ROCH2 OH, where the latter compound
spontaneously decomposed to ROH and HCHO, was observed during the reaction of the
supramolecular complex (met-hemoCD3) with cumene hydroperoxide in aqueous
solution. Met-hemoCD3 is composed of meso-tetrakis(4
sulfonatophenyl)porphinatoiron(III) (FeIII TPPS) and a per-O-methylated beta
cyclodextrin dimer having an -OCH2 PyCH2 O- linker (Py=pyridine-3,5-diyl). The
O=FeIV TPPS complex was formed by the reaction of met-hemoCD3 with cumene
hydroperoxide, and isolated by gel-filtration chromatography. Although the
isolated O=FeIV TPPS complex in the cyclodextrin cage was stable in aqueous
solution at 25 degrees C, it was gradually converted to FeII TPPS (t1/2 =7.6 h).
This conversion was accompanied by oxidative O-demethylation of an OCH3 group in
the cyclodextrin dimer. The results indicated that hydrogen abstraction by O=FeIV
TPPS from ROCH3 yields HO-FeIII TPPS and ROCH2. . This was followed by radical
coupling to afford FeII TPPS and ROCH2 OH. The hemiacetal (ROCH2 OH) immediately
decomposed to ROH and HCHO. This study revealed the ability of oxoferryl
porphyrin to induce two-electron oxidation.
PMID- 27616337
TI - Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance
T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of
Parkinson's disease.
AB - The role of dorsal hippocampus (DH) serotonin6 (5-HT6) receptors in memory is
unknown, particularly in memory impairment of Parkinson's disease. We tested here
effects of activation and blockade of DH 5-HT6 receptors on working and
hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions
of the medial forebrain bundle. The lesion induced working and hippocampus
dependent memory impairments as measured by the T-maze rewarded alternation and
hole-board tests, and decreased dopamine (DA) levels in the striatum, medial
prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT6 receptor
agonist WAY208466 (1.5, 3 and 6ug/rat) did not change choice accuracy and the
number of head-dippings when re-exposure to hole-board in sham-operated rats,
while 5-HT6 receptor antagonist SB258585 (4ug/rat) increased choice accuracy and
decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3
and 6ug/rat) and SB258585 (2 and 4ug/rat) increased choice accuracy and decreased
the number of head-dippings. Neurochemical results showed that intra-DH injection
of WAY208466 or SB258585 produced significant effects on DA and noradrenaline
(NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA
-47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466:
lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala
(WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated,
NA 183%); however, 5-HT levels in these brain regions were not changed. These
findings suggest DA depletion plays a key role in working and hippocampus
dependent memory impairments, and 5-HT6 receptors in the DH are involved in the
regulation of the memories.
PMID- 27616340
TI - Characterization of the Diabetes Population is Essential.
PMID- 27616339
TI - SAF score and mortality in NAFLD after up to 41 years of follow-up.
AB - BACKGROUND AND AIMS: A new score for the histological severity of nonalcoholic
fatty liver disease (NAFLD), called SAF (Steatosis, Activity and Fibrosis) has
been developed. We aimed to evaluate the impact of this score on overall
mortality. METHODS: We used data from 139 patients with biopsy-proven NAFLD. All
biopsies were graded according to the SAF scoring system and disease severity was
classified as mild, moderate or severe. Causes of death were extracted from a
national, population-based register. A Cox regression model, adjusted for sex,
body mass index (BMI) and diabetes mellitus type 2, was applied. RESULTS: At
baseline 35 patients presented with mild or moderate disease respectively, and 69
patients with severe disease. During follow-up (median 25.3 years, range 1.7
40.8) 74 patients died, 11 in the mild group (31%), 18 in the moderate group
(51%) and 45 in the severe group (65%), p = .002. Compared to patients with mild
disease, patients with moderate disease did not have a significant increase in
overall mortality (HR 1.83, 95%CI 0.89-3.77, p = .10). Patients with severe
disease had a significant increase in mortality (HR 2.65, 95%CI 1.19-5.93, p =
.017). However, when adjusting for fibrosis stage, significance was lost (HR
1.85, 95%CI 0.76-4.54, p = .18). NASH, defined as per the FLIP algorithm, was not
associated with mortality compared to not having NASH (HR 1.46, 95%CI 0.74-2.90,
p = .28). CONCLUSIONS: After adjustment for fibrosis, the SAF score was not
associated with increased mortality in NAFLD. This finding should be corroborated
in larger cohorts with similar follow-up time.
PMID- 27616338
TI - Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral
ventrolateral medulla of spontaneously hypertensive rats.
AB - Increased activity of the sympathetic nervous system has been highlighted as a
key factor that contributes to the development and maintenance of arterial
hypertension. However, the factors that precipitate sustained increases in
sympathetic activity remain poorly understood. Resting tissue oxygen partial
pressure (PtO2) in the brainstem of anesthetized spontaneously hypertensive rats
(SHRs) has been shown to be lower than in normotensive rats despite normal levels
of arterial PO2. A hypoxic environment in the brainstem has been postulated to
activate astroglial signalling mechanisms in the rostral ventrolateral medulla
(RVLM) which in turn increase the excitability of presympathetic neuronal
networks. In this study, we assessed the expression of indirect markers of tissue
hypoxia and astroglial cell activation in the RVLM of SHRs and age-matched
normotensive Wistar rats. Immunohistochemical labelling for hypoxia-induced
factor-1alpha (HIF-1alpha) and bound pimonidazole adducts revealed the presence
of tissue hypoxia in the RVLM of SHRs. Double immunostaining showed co
localization of bound pimonidazole labelling in putative presympathetic C1
neurons and in astroglial cells. Quantification of glial fibrillary acidic
protein (GFAP) immunofluorescence showed relatively higher number of astrocytes
and increased GFAP mean grey value density, whilst semi-quantitative analysis of
skeletonized GFAP-immunoreactive processes revealed greater % area covered by
astrocytic processes in the RVLM of adult SHRs. In conclusion, the morphological
findings of tissue hypoxia and astrogliosis within brainstem presympathetic
neuronal networks in the SHR support previous observations, showing that low
brainstem PtO2 and increased astroglial signalling in the RVLM play an important
role in pathological sympathoexcitation associated with the development of
arterial hypertension.
PMID- 27616341
TI - Comparison of Inhospital and 12- and 36-Month Outcomes After Acute Coronary
Syndrome in Men Versus Women <40 Years (from the PL-ACS Registry).
AB - The study was aimed to compare the characteristics and inhospital and 12- and 36
month outcomes of men and women <40 years with acute coronary syndrome (ACS). The
analysis involved 932 patients <40 years with ACS in the Silesia region enrolled
into the ongoing, prospective Polish Registry of Acute Coronary Syndromes from
January 2006 to December 2014. The composite end point involved death, recurrence
of ACS, a need for percutaneous coronary intervention, and coronary artery bypass
graft surgery within 12 and 36 months after ACS. Compared with men, women <40
years were less frequently smokers (66.1% vs 55.4%, p = 0008), had older average
age (35.6 +/- 4.2 vs 34.7 +/- 4.4, p = 0.002), more often had unstable angina at
admission (29.1% vs 19.3%, p <0.001), and less frequently had ST-elevation
myocardial infarction: 41.3% versus 51.3%, p = 0.02, at admission. There was no
significant difference in the mortality (4.8% vs 3.1%, p = 0.29) and the
composite end point (21.6% vs 16.0%, p = 0.14) within 12 months after ACS.
Compared with men, women had a higher incidence of the composite end point (28.4%
vs 20.1%, p = 0.04) and indicated a tendency of a higher mortality within the 36
month follow-up period (9.2% vs 5.0%, p = 0.055). Female gender turned out to be
an independent risk factor of death in the multivariate analysis (hazard ratio
2.76, 95% confidence interval 1.21 to 6.31, p <0.016). In conclusion, women had a
higher incidence of the composite end point and showed a tendency toward a higher
mortality than the men within the 36-month follow-up period.
PMID- 27616342
TI - Altered function in medial prefrontal cortex and nucleus accumbens links to
stress-induced behavioral inflexibility.
AB - The medial prefrontal cortex (mPFC) and its output area, the nucleus accumbens
(NAc), are implicated in mediating attentional set-shifting. Patients with
posttraumatic stress disorder (PTSD) exhibit difficulties in the disengagement of
attention from traumatic cues, which is associated with impairments in set
shifting ability. However, unknown is whether alterations in corticostriatal
function underlie deficits in this behavioral flexibility in individuals with
PTSD. An animal model of single prolonged stress (SPS) has been partially
validated as a model for PTSD, in which SPS rats recapitulate the
pathophysiological abnormalities and behavioral characteristics of PTSD. In the
present study, we firstly found that exposure to SPS impaired the ability in the
shift from visual-cue learning to place response discrimination in rats.
Conversely, SPS induced no effect on a place-to-cue set-shifting performance.
Based on SPS-impaired set-shifting model, we used Western blot and
immunofluorescent approaches to clarify SPS-induced alternations in synaptic
plasticity and neuronal activation in the mPFC and NAc. Rats that were subjected
to SPS exhibited a large increase in pSer845-GluA1 and total GluA1 levels in the
mPFC, while no significant change in the NAc. We further found that exposure to
SPS significantly decreased c-Fos expression in the NAc core but not the shell
after set-shifting behavior. Whereas, enhanced c-Fos expression was observed in
prelimbic and infralimbic cortices. Collectively, these findings suggest that
abnormal hyperactivity in the mPFC and dysfunction in the NAc core underlie long
term deficits in executive function after traumatic experience, which might play
an important role in the development of PTSD symptoms.
PMID- 27616343
TI - Pupillary responses and memory-guided visual search reveal age-related and
Alzheimer's-related memory decline.
AB - Episodic memory - composed of memory for unique spatiotemporal experiences - is
known to decline with aging, and even more severely in Alzheimer 's disease (AD).
Memory for trial-unique objects in spatial scenes depends on the integrity of the
hippocampus and interconnected structures that are among the first areas affected
in AD. We reasoned that memory for objects-in-scenes would be impaired with
aging, and that further impairments would be observed in AD. We asked younger
adults, healthy older adults, older adults at-risk for developing cognitive
impairments, and older adults with probable early AD to find changing items
('targets') within images of natural scenes, measuring repeated-trial changes in
search efficiency and pupil diameter. Compared to younger adults, older adults
took longer to detect target objects in repeated scenes, they required more
fixations and those fixations were more dispersed. Whereas individuals with AD
showed some benefit of memory in this task, they had substantially longer
detection times, and more numerous, dispersed fixations on repeated scenes
compared to age-matched older adults. Correspondingly, pupillary responses to
novel and repeated scenes were diminished with aging and further in AD, and the
memory-related changes were weaker with aging and absent in AD. Our results
suggest that several nonverbal measures from memory-guided visual search tasks
can index aging and Alzheimer's disease status, including pupillary dynamics. The
task measurements are sensitive to the integrity of brain structures that are
associated with Alzheimer's-related neurodegeneration, the task is well tolerated
across a range of abilities, and thus, it may prove useful in early diagnostics
and longitudinal tracking of memory decline.
PMID- 27616344
TI - 5-Hydroxytryptamine2A/2C receptors of nucleus raphe magnus and
gigantocellularis/paragigantocellularis pars alpha reticular nuclei modulate the
unconditioned fear-induced antinociception evoked by electrical stimulation of
deep layers of the superior colliculus and dorsal periaqueductal grey matter.
AB - The electrical stimulation of the dorsolateral columns of the periaquedutal grey
matter (dlPAG) or deep layers of the superior colliculus (dlSC) evokes defensive
behaviours followed by an antinociceptive response. Monoaminergic brainstem
reticular nuclei are suggested to comprise the endogenous pain modulatory system.
The aim of the present work was to investigate the role played by 5-HT2 subfamily
of serotonergic receptors of the nucleus raphe magnus (NRM) and the
gigantocellularis/paragigantocellularis pars alpha reticular nuclei (Gi/PGialpha)
in the elaboration of instinctive fear-induced antinociception elicited by
electrical stimulation of dlPAG or of dlSC. The nociceptive thresholds were
measured by the tail-flick test in Wistar rats. The 5-HT2A/2C-serotonergic
receptors antagonist ritanserin was microinjected at different concentrations
(0.05, 0.5 and 5.0MUg/0.2MUL) either in Gi/PGialpha or in NRM. The blockade of 5
HT2 receptors in both Gi/PGialpha and NRM decreased the innate fear-induced
antinociception elicited by electrical stimulation of the dlSC or the dlPAG.
These findings indicate that serotonin is involved in the hypo-algesia induced by
unconditioned fear-induced behavioural responses and the 5-HT2A/2C-serotonergic
receptor subfamily in neurons situated in the Gi/PGialpha complex and NRM are
critically recruited in pain modulation during the panic-like emotional
behaviour.
PMID- 27616345
TI - Filial responses as predisposed and learned preferences: Early attachment in
chicks and babies.
AB - To what extent are filial responses the outcome of spontaneous or acquired
preferences? The case of domestic chicks illustrates the connection between
predisposed and learned knowledge in early social responses. In the absence of
specific experience, chicks prefer to approach objects that are more similar to
natural social partners (e.g. they prefer face-like configurations, biological
motion, self-propelled objects and those that move at variable speed).
Spontaneous preferences are complemented by filial imprinting, a powerful
learning mechanism that enables chicks to quickly learn the features of specific
social partners. While neurobiological studies have clarified that the substrates
of spontaneous and learned preferences are at least partially distinct in chicks,
evidence shows that spontaneous preferences might orient and facilitate
imprinting on animate stimuli, such as the mother hen, and that hormones
facilitate and strengthen preferences for predisposed stimuli. Preferences
towards animate stimuli are observed in human neonates as well. The remarkable
consistency between the perceptual cues attended to by newborn babies and naive
chicks suggests that the attentional biases observed in babies are unlikely to
result from very rapid post-natal learning, and confirms that research on
precocial species can inform and guide human infant research with regards to both
typical and atypical development. This has potentially important biomedical
implications, opening new possibilities for the early detection of subjects at
risk for autism spectrum disorders. We show how the parallel investigation of
predispositions in naive chicks and human infants, both benefiting from contact
with social partners since the beginning of life, has greatly improved our
understanding of early responses to social stimuli at the behavioural and
neurobiological level.
PMID- 27616346
TI - Clinical trials in pediatric neuro-oncology: what is missing and how we can
improve.
AB - Brain tumors are the most common solid tumor in childhood, yet outcomes vary
dramatically. High-grade gliomas have dismal outcomes with poor survival. By
contrast, low-grade gliomas, have high survival rates, but children suffer from
morbidity of tumor burden and therapy-associated side effects. In this article,
we discuss how current trial designs often miss the opportunity to include end
points beyond tumor response and thus fail to offer complete assessments of
therapeutic approaches. Quality of life, neurocognitive function and
neurofunctional deficits need to be considered when assessing overall success of
a therapy. Herein, we identify specific end points that should be included in the
interpretation of clinical trial results and accordingly, offer a more
comprehensive approach to treatment decision-making.
PMID- 27616348
TI - The relationship between positive psychological characteristics and longer
telomeres.
AB - OBJECTIVE: Longer telomeres are associated with better health and longevity. This
research investigated the relationship between positive psychological
dispositional traits and telomere length. Positive traits examined were typical
high positive affect, typical low negative affect, life satisfaction, trait
mindfulness, trait emotional intelligence, general self-efficacy and optimism.
DESIGN AND MEASURES: One hundred and twenty women and men, with a mean age of
40.92, completed measures of positive characteristics and provided samples for
telomere length analysis. RESULTS: Together the positive dispositional
characteristics explained significant variance in telomere length, R = .40. Among
the individual characteristics, greater optimism and higher emotional
intelligence were associated with longer telomeres after adjustment for age and
gender and the association between optimism and telomere length remained
significant after adjusting for age and gender as well as the other positive
characteristics, with a partial correlation r of .30. CONCLUSION: These results
in conjunction with previous research findings provide a platform for further
exploration of biological pathways connecting positive characteristics such as
optimism to telomere length and investigation of the impact of increasing a
characteristic such as optimism on telomere functioning.
PMID- 27616347
TI - [Usefulness of rehabilitation in inflammatory myopathies].
AB - Rehabilitation, for a long time not recommended, seems today to hold a prominent
place within the therapeutic arsenal of inflammatory myopathies. The difficulty
of its evaluation, apart from the low prevalence of these diseases, lies in a
triple heterogeneity: first that distinguishing the different forms of
inflammatory myopathies and the phase where they are active; second, that
concerning the endpoint considered to assess the efficiency of the intervention;
lastly, the diversity of the rehabilitation programs that can be undertaken.
Between 1993 and 2016, about 30 studies estimating the rehabilitation of
inflammatory myopathies have been published, among which five randomized
controlled trials, four controlled trials, 15 open studies, and seven case
reports. All these studies evidence the safety of rehabilitation and some show a
significant improvement of the criteria estimating the activity of the disease,
its functional impact or the impairment of quality of life and the limitation in
daily life activities triggered by the disease. The rehabilitation, whether
aerobic, anaerobic or mixed, must today systematically be associated with the
pharmaceutic treatment proposed to patients affected by inflammatory myopathies.
Other studies are necessary to optimize the rehabilitation methods, to understand
their effects and action, and to quantify their impact and provide more
trustworthy evidence.
PMID- 27616349
TI - Density Functional Theory Calculations Support the Additive Nature of Ligand
Contributions to the pKa of Iron Hydride Phosphine Carbonyl Complexes.
AB - The acid dissociation constant Ka of a transition-metal hydride complex is a key
thermodynamic quantity for evaluating reactivity and stability of the complexes
and their conjugate bases in stoichiometric and catalytic reactions. It can be
estimated using a simple ligand acidity constant (LAC) empirical equation for a
wide range of complexes. Here, we provide the first density functional theory
(DFT) study that supports the additive nature of ligand contributions to the pKa
of metal hydride complexes. Specifically, the pKa values of iron hydride
complexes [FeH(CO)x(PR3)(5-x)]+ in either tetrahydrofuran or dichloromethane
solutions are estimated using the LAC method and DFT calculations. There is a
linear correlation between these two methods, and both predict a surprisingly
linear increase in pKa over a wide range from approximately -15 for x = 5 to
approximately 40 for x = 0. The LAC equation predicts that pKaTHF or pKaDCM
increases by 9 units with the replacement of each CO ligand with a
trialkylphosphine ligand in a stepwise fashion, whereas the DFT calculations
predict the step size will be approximately 11. The two methods agree with pKDCM
data available for x = 3 and qualitative data for x = 1 and 0, but further
quantitative measurements over a wider range are needed to firmly establish the
trend. The free energy of protonation and the energy of the highest occupied
molecular orbital of Fe(CO)x(PR3)(5-x) (mainly nonbonding d electrons) increase
linearly with phosphine substitution, and this increases the pKa value as
observed.
PMID- 27616352
TI - A tree of tree frogs around the Black Sea.
AB - Speciation, the process by which one species evolves into two or more, is a major
focus of ongoing debate, particularly regarding the geographic context in which
it occurs. Geographic models of speciation tend to fall into discrete categories,
typically referred to as allopatric, parapatric and sympatric speciation,
according to whether two groups evolve reproductive isolation while
geographically isolated, differentiated but connected by gene flow, or completely
co-occurring. Yet molecular studies indicate that full development of
reproductive isolation can take very long compared with the timescale at which
climatic oscillations occur, such that the geographic context of differentiating
forms might change often during the long process to full species. Studies of
genetic relationships across the ranges of organisms with low-dispersal distances
have the potential to reveal these complex histories. In a particularly elegant
example in this issue, Dufresnes et al. () use genetic variation and ecological
niche modelling to show that a ring of populations of the eastern tree frog (Hyla
orientalis) surrounding the Black Sea had a complex history of geographic
differentiation. Alternating phases of geographic fragmentation and phases of
gene flow between neighbouring populations have produced a pattern of gradual
genetic change connecting the western, southern and eastern sides of the ring,
with the northwestern and northeastern forms being most differentiated. In the
north, a population in Crimea appears to have been produced through mixture of
the two extreme forms. The overall genetic relationships are reminiscent of those
found in ring species, which have been used as prime demonstrations of the
process of speciation. The difference, however, is that the terminal forms appear
to have mixed rather than be reproductively isolated, although more research is
needed to infer whether there might be some reproductive isolation on the
northern side of the ring.
PMID- 27616353
TI - Shift of grey seal subspecies boundaries in response to climate, culling and
conservation.
AB - Identifying the processes that drive changes in the abundance and distribution of
natural populations is a central theme in ecology and evolution. Many species of
marine mammals have experienced dramatic changes in abundance and distribution
due to climatic fluctuations and anthropogenic impacts. However, thanks to
conservation efforts, some of these species have shown remarkable population
recovery and are now recolonizing their former ranges. Here, we use
zooarchaeological, demographic and genetic data to examine processes of
colonization, local extinction and recolonization of the two northern European
grey seal subspecies inhabiting the Baltic Sea and North Sea. The
zooarchaeological and genetic data suggest that the two subspecies diverged
shortly after the formation of the Baltic Sea approximately 4200 years bp,
probably through a gradual shift to different breeding habitats and phenologies.
By comparing genetic data from 19th century pre-extinction material with that
from seals currently recolonizing their past range, we observed a marked
spatiotemporal shift in subspecies boundaries, with increasing encroachment of
North Sea seals on areas previously occupied by the Baltic Sea subspecies.
Further, both demographic and genetic data indicate that the two subspecies have
begun to overlap geographically and are hybridizing in a narrow contact zone. Our
findings provide new insights into the processes of colonization, extinction and
recolonization and have important implications for the management of grey seals
across northern Europe.
PMID- 27616350
TI - Fusing Sensor Paradigms to Acquire Chemical Information: An Integrative Role for
Smart Biopolymeric Hydrogels.
AB - The Information Age transformed our lives but it has had surprisingly little
impact on the way chemical information (e.g., from our biological world) is
acquired, analyzed and communicated. Sensor systems are poised to change this
situation by providing rapid access to chemical information. This access will be
enabled by technological advances from various fields: biology enables the
synthesis, design and discovery of molecular recognition elements as well as the
generation of cell-based signal processors; physics and chemistry are providing
nano-components that facilitate the transmission and transduction of signals rich
with chemical information; microfabrication is yielding sensors capable of
receiving these signals through various modalities; and signal processing
analysis enhances the extraction of chemical information. The authors contend
that integral to the development of functional sensor systems will be materials
that (i) enable the integrative and hierarchical assembly of various sensing
components (for chemical recognition and signal transduction) and (ii) facilitate
meaningful communication across modalities. It is suggested that stimuli
responsive self-assembling biopolymers can perform such integrative functions,
and redox provides modality-spanning communication capabilities. Recent progress
toward the development of electrochemical sensors to manage schizophrenia is used
to illustrate the opportunities and challenges for enlisting sensors for chemical
information processing.
PMID- 27616351
TI - WEE1 inhibition in pancreatic cancer cells is dependent on DNA repair status in a
context dependent manner.
AB - Pancreatic ductal adenocarcinoma (PDA) is a lethal disease, in part, because of
the lack of effective targeted therapeutic options. MK-1775 (also known as
AZD1775), a mitotic inhibitor, has been demonstrated to enhance the anti-tumor
effects of DNA damaging agents such as gemcitabine. We evaluated the efficacy of
MK-1775 alone or in combination with DNA damaging agents (MMC or oxaliplatin) in
PDA cell lines that are either DNA repair proficient (DDR-P) or deficient (DDR
D). PDA cell lines PL11, Hs 766T and Capan-1 harboring naturally selected
mutations in DNA repair genes FANCC, FANCG and BRCA2 respectively, were less
sensitive to MK-1775 as compared to two out of four representative DDR-P (MIA
PaCa2 and PANC-1) cell lines. Accordingly, DDR-P cells exhibit reduced
sensitivity to MK-1775 upon siRNA silencing of DNA repair genes, BRCA2 or FANCD2,
compared to control cells. Only DDR-P cells showed increased apoptosis as a
result of early mitotic entry and catastrophe compared to DDR-D cells. Taken
together with other recently published reports, our results add another level of
evidence that the efficacy of WEE1 inhibition is influenced by the DNA repair
status of a cell and may also be dependent on the tumor type and model evaluated.
PMID- 27616354
TI - A comparative analysis of sperm selection procedures prior to cryopreservation
for Nili-Ravi buffalo bull (Bubalus bubalis) semen-: Assessment of its impact on
post-thaw sperm functional quality.
AB - Sperm selection techniques have been developed to get sperm suspensions enriched
in motile and functional cells. Studies show that selection before
cryopreservation improves post-thaw quality of cryopreserved sperm but
information on buffalo bull sperm is scarce. The study was aimed to 1) perform a
comparative analysis of sperm selection procedures; Swim-Up (SU), SephadexTM-G15
Filtration (S-G15) or Glass Wool Filtration (GWF) for total and motile cell
recovery, 2) to assess the impact of sperm selection prior to cryopreservation on
sperm quality (motility, morphology, cell membrane and normal apical ridge,
viability and livability, chromatin integrity) and sperm functionality (Embryo
Cleavage after IVF with selected sperm) in post-thawed suspensions of buffalo
bull sperm. Semen was collected from 5 Nili Ravi buffalo bulls maintained at the
Semen Production Unit Qadirabad, District Sahiwal, Pakistan. Ejaculates were
divided into four aliquots for SU, S-G15 and GWF and control. After sperm
selection, total and motile sperm recovery was highest in GWF samples (total
sperm=84.08+/-8.39%; motile sperm=80.42+/-3.57%). An improvement (P<0.05) in all
post-thaw parameters was observed in S-G15-selected sperm and, in some parameters
in GWF-filtered sperm suspensions compared to control. The highest (P<0.05)
embryo cleavage rate (%) was achieved with frozen-thawed sperm selected with S
G15 prior to cryopreservation (44.72+/-4.18) compared to control (21.98+/-3.00).
In conclusion, post thaw sperm quality was improved after sperm selection from
fresh buffalo bull semen through S-G15 and GWF procedures compared to SU and
control while, the fertility rate (cleavage rate) was improved with sperm
processed using the S-G15 procedure.
PMID- 27616355
TI - Effect of the meiotic inhibitor cilostamide on resumption of meiosis and
cytoskeletal distribution in buffalo oocytes.
AB - Improving the quality of in vitro maturated buffalo oocytes is essential for
embryo production. We report here the effects on microtubules and microfilaments
in oocytes and embryo development that result from treating buffalo oocytes with
the phosphodiesterase 3 (PDE3) inhibitor cilostamide. Addition of 20MUM or 50MUM
cilostamide for 24h during in vitro maturation showed no differences in the
percentage of oocytes arrested at the germinal vesicle (GV) stage. When 20MUM
cilostamide was added to the pre-maturation culture for 6h, 12h or 24h and
continued for another 24h without cilostamide, oocytes resumed meiosis, but with
significantly lower (P<0.01) maturation rates in the 24h group than that in the
other two groups. During oocyte maturation in vitro, no microtubules were
detected before GV breakdown (GVBD). After GVBD, microtubules combined with
condensed chromatin to form the meiotic metaphase spindle. Microfilaments covered
a thick area around the cellular cortex and overlying chromosomes. Cilostamide
had no effects on microtubules and microfilaments in metaphase II oocytes, and
there were no significant differences in the rates of cleavage, blastocyst
formation and number of blastocyst cells between oocytes treated pre-maturation
with inhibitor for 6h and those of the control group (P>0.05). In summary,
cilostamide reversibly arrested the resumption of meiosis without any adverse
impact on the dynamic changes in microtubules and microfilaments in buffalo
oocytes and their in vitro developmental capacity.
PMID- 27616356
TI - Mechanism of allele specific assembly and disruption of master regulator
transcription factor complexes of NF-KBp50, NF-KBp65 and HIF1a on a non-coding
FAS SNP.
AB - A challenging question in genetics is to understand the molecular function of non
coding variants of the genome. By using differential EMSA, ChIP and functional
genome analysis, we have found that changes in transcription factors (TF)
apparent binding affinity and dissociation rates are responsible for allele
specific assembly or disruption of master TFs: we observed that NF-KBp50, NF
KBp65 and HIF1a bind with an affinity of up to 10 fold better to the C-allele
than to the T-allele of rs7901656 both in vivo and in vitro. Furthermore, we
showed that NF-KBp50, p65 and HIF1a form higher order heteromultimeric complexes
overlapping rs7901656, implying synergism of action among TFs governing cellular
response to infection and hypoxia. With rs7901656 on the FAS gene as a paradigm,
we show how allele specific transcription factor complex assembly and disruption
by a causal variant contributes to disease and phenotypic diversity. This finding
provides the highly needed mechanistic insight into how the molecular etiology of
regulatory SNPs can be understood in functional terms.
PMID- 27616358
TI - Transcriptional activity of the short gastrulation primary enhancer in the
ventral midline requires its early activity in the presumptive neurogenic
ectoderm.
AB - The short gastrulation (sog) shadow enhancer directs early and late sog
expression in the neurogenic ectoderm and the ventral midline of the developing
Drosophila embryo, respectively. Here, evidence is presented that the sog primary
enhancer also has both activities, with the late enhancer activity dependent on
the early activity. Computational analyses showed that the sog primary enhancer
contains five Dorsal (Dl)-, four Zelda (Zld)-, three Bicoid (Bcd)-, and no Single
minded (Sim)-binding sites. In contrast to many ventral midline enhancers, the
primary enhancer can direct lacZ expression in the ventral midline as well as in
the neurogenic ectoderm without a canonical Simbinding site. Intriguingly, the
impaired transcriptional synergy between Dl and either Zld or Bcd led to aberrant
and abolished lacZ expression in the neurogenic ectoderm and in the ventral
midline, respectively. These findings suggest that the two enhancer activities of
the sog primary enhancer are functionally consolidated and geographically
inseparable. [BMB Reports 2016; 49(10): 572-577].
PMID- 27616359
TI - CRISPR as a strong gene editing tool.
AB - Clustered regularly-interspaced short palindromic repeats (CRISPR) is a new and
effective genetic editing tool. CRISPR was initially found in bacteria to protect
it from virus invasions. In the first step, specific DNA strands of virus are
identified by guide RNA that is composed of crRNA and tracrRNA. Then RNAse III is
required for producing crRNA from pre-crRNA. In The second step, a
crRNA:tracrRNA:Cas9 complex guides RNase III to cleave target DNA. After cleavage
of DNA by CRISPR-Cas9, DNA can be fixed by Non- Homologous End Joining (NHEJ) and
Homology Directed Repair (HDR). Whereas NHEJ is simple and random, HDR is much
more complex and accurate. Gene editing by CRISPR is able to be applied to
various biological field such as agriculture and treating genetic diseases in
human. [BMB Reports 2017; 50(1): 20-24].
PMID- 27616360
TI - Essentialist beliefs: Understanding contact with and attitudes towards lesbian
and gay individuals.
AB - Sexual prejudice remains a widespread problem worldwide. Past research
demonstrates that cross-orientation contact (contact between heterosexuals and
lesbian/gay individuals) reduces sexual prejudice among heterosexuals, especially
when contact is high quality. This study extends the literature on the
relationship between cross-orientation contact and sexual prejudice and the
mediation of this relationship by intergroup anxiety by examining the role of a
key ideology - essentialist beliefs about homosexuality (immutability,
universality, and discreteness beliefs). Findings indicate that the mediation of
the relationship between cross-orientation contact and sexual prejudice by
intergroup anxiety differs by level of essentialist beliefs. Additionally, the
relationship between cross-orientation contact and sexual prejudice appears to be
mediated by essentialist beliefs as well as intergroup anxiety. These results
suggest that individuals who endorse essentialist beliefs commonly associated
with increased bias (high discreteness and low immutability and universality
beliefs) may benefit the most from cross-orientation contact and resultant
decreases in intergroup anxiety. Further, decreasing essentialist beliefs
generally associated with increased bias may be a mechanism through which cross
orientation contact reduces sexual prejudice. Implications and future directions
are discussed.
PMID- 27616357
TI - Protective effects of Tat-NQO1 against oxidative stress-induced HT-22 cell
damage, and ischemic injury in animals.
AB - Oxidative stress is closely associated with various diseases and is considered to
be a major factor in ischemia. NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is
a known antioxidant protein that plays a protective role in various cells against
oxidative stress. We therefore investigated the effects of cell permeable Tat
NQO1 protein on hippocampal HT-22 cells, and in an animal ischemia model. The Tat
NQO1 protein transduced into HT-22 cells, and significantly inhibited against
hydrogen peroxide (H2O2)-induced cell death and cellular toxicities. Tat-NQO1
protein inhibited the Akt and mitogen activated protein kinases (MAPK) activation
as well as caspase-3 expression levels, in H2O2 exposed HT-22 cells. Moreover,
Tat-NQO1 protein transduced into the CA1 region of the hippocampus of the animal
brain and drastically protected against ischemic injury. Our results indicate
that Tat-NQO1 protein exerts protection against neuronal cell death induced by
oxidative stress, suggesting that Tat-NQO1 protein may potentially provide a
therapeutic agent for neuronal diseases. [BMB Reports 2016; 49(11): 617-622].
PMID- 27616361
TI - Investigation of risk factors for mortality in aged guide dogs: A retrospective
cohort study.
AB - The overall median lifespan of domestic dogs has been estimated to 9-12 years,
but little is known about risk factors for mortality in aged and a priori healthy
dogs. The objective of this retrospective cohort study was to determine which
characteristics are associated with mortality in aged and a priori healthy guide
dogs, in a retrospective cohort study of 116 guide dogs followed from a
systematic geriatric examination at the age of 8-10 years old. A geriatric grid
collected the clinical data and usual biological parameters were measured at the
time of examination. Univariate (Kaplan-Meier estimates) and multivariable (Cox
proportional hazard model) survival analyses were used to assess the associations
with time to all-cause death. The majority of dogs were Golden Retrievers (n=48)
and Labrador Retrievers (n=27). Median age at geriatric examination was 8.9
years. A total of 76 dogs died during follow-up, leading to a median survival
time from geriatric examination of 4.4 years. After adjustment for demographic
and biological variables, an increased alanine amionotransferase level (adjusted
Hazard Ratio (adjusted HR), 6.2; 95% confidence interval [95%CI], 2.0-19.0;
P<0.01), presenting skin nodules (adjusted HR, 1.9; 95% CI, 1.0-3.4; P=0.04), and
not being a Labrador Retriever (adjusted HR, 3.3; 95%CI, 1.4-10; P<0.01) were
independently associated with a shorter time to death. This study documents
independent associations of alanine aminotransferase level, skin nodules and
breed with mortality in aged guide dogs. These results may be useful for
preventive medical care when conducting a geriatric examination in working dogs.
PMID- 27616362
TI - Response to "Can portion-controlled prepackaged foods promote weight loss?"
PMID- 27616420
TI - Multishelled NiO Hollow Microspheres for High-performance Supercapacitors with
Ultrahigh Energy Density and Robust Cycle Life.
AB - Multishelled NiO hollow microspheres for high-performance supercapacitors have
been prepared and the formation mechanism has been investigated. By using resin
microspheres to absorb Ni(2+) and subsequent proper calcinations, the shell
numbers, shell spacing and exterior shell structure were facilely controlled via
varying synthetic parameters. Particularly, the exterior shell structure that
accurately associated with the ion transfer is finely controlled by forming a
single shell or closed exterior double-shells. Among multishelled NiO hollow
microspheres, the triple-shelled NiO with an outer single-shelled microspheres
show a remarkable capacity of 1280 F g(-1) at 1 A g(-1), and still keep a high
value of 704 F g(-1) even at 20 A g(-1). The outstanding performances are
attributed to its fast ion/electron transfer, high specific surface area and
large shell space. The specific capacitance gradually increases to 108% of its
initial value after 2500 cycles, demonstrating its high stability. Importantly,
the 3S-NiO-HMS//RGO@Fe3O4 asymmetric supercapacitor shows an ultrahigh energy
density of 51.0 Wh kg(-1) at a power density of 800 W kg(-1), and 78.8%
capacitance retention after 10,000 cycles. Furthermore, multishelled NiO can be
transferred into multishelled Ni microspheres with high-efficient H2 generation
rate of 598.5 mL H2 min(-1) g(-1)Ni for catalytic hydrolysis of NH3BH3 (AB).
PMID- 27616421
TI - Radioactive particles released to the environment from the Fukushima reactors
Confirmation is still needed.
AB - After severe nuclear events, a major fraction of refractory radionuclides such as
U and Pu are released to the environment in the form of radioactive particles.
After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, Pu isotope
ratio signals different from that of global fallout have been reported,
indicating that spent fuel particles have been released from the reactors or
reactor vessels. Radioactive particles containing (37) Cs and other volatile
radionuclides, as well as a series of stable refractory metals (Cs, Fe, Zn, U,
etc.), have been identified by several authors claiming that these particles
originated from the FDNPP fuel. If so, long-lived radioactive isotopes of the
refractory metals should have been identified in these particles. It is therefore
most probable that volatile radionuclides released as gases during the accidents
have deposited on available surfaces such as fly ash, forming condensation
particles during release or transport. If spent fuel particles have been
deposited in the FDNPP surroundings, information on particle characteristics
influencing ecosystem transport, uptake, and effects is essential for assessing
environmental impact and risk. More emphasis should therefore be put on the
identification of hot spots in the FDNPP environment followed by the
characterization of radioactive particles using nanoanalytical-microanalytical
techniques to support environmental monitoring, as recommended in the present
study. Integr Environ Assess Manag 2016;12:687-689. (c) 2016 SETAC.
PMID- 27616422
TI - The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema
Association.
AB - To assess the patient-level and societal burden of atopic dermatitis, we
comprehensively reviewed the literature related to quality of life, social,
economic, academic, and occupational impacts. Atopic dermatitis has profound
impacts on patient and family quality of life. A conservative estimate of the
annual costs of atopic dermatitis in the United States is $5.297 billion (in 2015
USD). People with atopic dermatitis may change their occupation because of their
skin disease. Research gaps include quality of life assessments outside of
tertiary care centers, impacts on partners and families of adult patients, and
updated comprehensive cost estimates.
PMID- 27616423
TI - Somatosensory map expansion and altered processing of tactile inputs in a mouse
model of fragile X syndrome.
AB - Fragile X syndrome (FXS) is a common inherited form of intellectual disability
caused by the absence or reduction of the fragile X mental retardation protein
(FMRP) encoded by the FMR1 gene. In humans, one symptom of FXS is
hypersensitivity to sensory stimuli, including touch. We used a mouse model of
FXS (Fmr1 KO) to study sensory processing of tactile information conveyed via the
whisker system. In vivo electrophysiological recordings in somatosensory barrel
cortex showed layer-specific broadening of the receptive fields at the level of
layer 2/3 but not layer 4, in response to whisker stimulation. Furthermore, the
encoding of tactile stimuli at different frequencies was severely affected in
layer 2/3. The behavioral effect of this broadening of the receptive fields was
tested in the gap-crossing task, a whisker-dependent behavioral paradigm. In this
task the Fmr1 KO mice showed differences in the number of whisker contacts with
platforms, decrease in the whisker sampling duration and reduction in the whisker
touch-time while performing the task. We propose that the increased excitability
in the somatosensory barrel cortex upon whisker stimulation may contribute to
changes in the whisking strategy as well as to other observed behavioral
phenotypes related to tactile processing in Fmr1 KO mice.
PMID- 27616425
TI - Gene therapy for Parkinson's disease: Disease modification by GDNF family of
ligands.
AB - Gene transfer is a promising drug delivery method of advanced therapeutic
entities for Parkinson's disease. One advantage over conventional therapies, such
as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific
expression of proteins with regenerative, disease-modifying and potentially
neuroprotective capacity. Several clinical trials have been performed to test the
capacity of glial-cell line derived neurotrophic factor and neurturin to rescue
degenerating dopaminergic neurons in the substantia nigra and their axon
terminals in the striatum by delivery of these neurotrophic factors either as
purified protein or by means of viral vector mediated gene delivery to the brain.
Although gene therapy approaches tested so far have been shown to be safe, none
met their primary endpoints in phase II clinical trials designed and powered to
test the efficacy of the intervention. Within the scope of this review we aim to
describe the state-of-the-art in the field, how different technical parameters
were translated from pre-clinical studies in non-human primates to clinical
trials, and what these trials taught us regarding important factors that may pave
the way to the success of gene therapy for the treatment of Parkinson's disease.
PMID- 27616427
TI - An Open-Cage Fullerene That Mimics the C60 H10 (5,5)-Carbon Nanotube Endcap to
Host Acetylene and Hydrogen Cyanide Molecules.
AB - Treatment of the open-cage fullerene C63 H4 NO2 (Ph)2 (Py)(N2 C6 H4 ) (1) with
methanol at 150 degrees C results in an orifice-enlargement reaction to give C69
H8 NO(CO2 Me)(Ph)(Py)(N2 C6 H4 ) (2). The overall yield from C60 to isolated 2 is
6.1 % (four steps). Compound 2 contains a 24-membered elliptic orifice that spans
8.45 A along the major axis and 6.37 A along the minor axis. The skeleton of 2
resembles the hypothetic C60 H10 (5,5)-carbon nanotube endcap. The cup-shaped
structure of 2 is able to include water, hydrogen cyanide, and acetylene, forming
H2 O@2, HCN@2, and C2 H2 @2, respectively. The molecular structures of H2 O@2 and
HCN@2 have been determined by X-ray crystallography. The 1 H NMR spectra reveal
substantial upfield shifts for the endohedral species, such as delta=-10.30 (for
H2 O), -2.74 and -14.26 (for C2 H2 ), and -1.22 ppm (for HCN), owing to the
strong shielding effects of the fullerene cage.
PMID- 27616426
TI - Membrane receptor cross talk in gonadotropin-, IGF-I-, and insulin-mediated
steroidogenesis in fish ovary: An overview.
AB - Gonadal steroidogenesis is critical for survival and reproduction of all animals.
The pathways that regulate gonadal steroidogenesis are therefore conserved among
animals from the steroidogenic enzymes to the intracellular signaling molecules
and G protein-coupled receptors (GPCRs) that mediate the activity of these
enzymes. Regulation of fish ovarian steroidogenesis in vitro by gonadotropin
(GtH) and GPCRs revealed interaction between adenylate cyclase and
calcium/calmodulin-dependent protein kinases (CaMKs) and also MAP kinase pathway.
Recent studies revealed another important pathway in GtH-induced fish ovarian
steroidogenesis: cross talk between GPCRs and membrane receptor tyrosine kinases.
Gonadotropin binding to Galphas-coupled membrane receptor in fish ovary leads to
production of cAMP which in turn trans-activate the membrane-bound epidermal
growth factor receptor (EGFR). This is followed by activation of ERK1/2 signaling
that promotes steroid production. Interestingly, GtH-induced trans-activation of
EGFR in the fish ovary uniquely requires matrix-metalloproteinase-mediated
release of EGF. Inhibition of these proteases blocks GtH-induced steroidogenesis.
Increased cAMP production in fish ovarian follicle upregulate follicular cyp19a1a
mRNA expression and aromatase activity leading to increased biosynthesis of
17beta-estradiol (E2). Evidence for involvement of SF-1 protein in inducing
cyp19a1a mRNA and aromatase activity has also been demonstrated. In addition to
GtH, insulin-like growth factor (IGF-I) and bovine insulin can alone induced
steroidogenesis in fish ovary. In intact follicles and isolated theca cells, IGF
I and insulin had no effect on GtH-induced testosterone and
17a,hydroxysprogeaterone production. GtH-stimulated E2 and 17,20bdihydroxy-4
pregnane 3-one production in granulosa cells however, was significantly increased
by IGF-I and insulin. Both IGF-I and insulin mediates their signaling via
receptor tyrosine kinases leading to activation of PI3 kinase/Akt and MAP kinase.
These kinase signals then activates steroidogenic enzymes which promotes steroid
production. PI3 kinase, therefore considered to be an initial component of the
signal transduction pathways which precedes MAP kinase in IGF-1 and
insulininduced steroidogenesis in fish ovary. Thus, investigation on the
mechanism of signal transduction regulating fish ovarian steroidogenesis have
shown that multiple, apparently independent signal transduction pathways are
needed to convey the message of single hormone or growth factor.
PMID- 27616428
TI - A novel magnetic-driven tissue retraction device for minimally invasive surgery.
AB - INTRODUCTION: The purpose of this work is to design and validate an innovative
magnetic-based device for tissue retraction for minimally invasive surgery.
MATERIAL AND METHODS: An intra-abdominal magnetic module is coupled with an
extracorporeal system for establishing a stable attraction, and consequently a
reliable tissue retraction. Once the retractor has been inserted into the
abdomen, tissue retraction is not constrained by a fixed access port, thus
guaranteeing a more flexible, safer and less invasive operation. The intra
abdominal unit is composed of an axial permanent magnet attached to a stainless
steel non-magnetic alligator clip by a traditional suturing thread. A
miniaturized mechanism to adjust the length of the suturing thread for
lengthening or shortening the distance between the tissue grasper and the
internal magnetic unit is included. A multiphysics approach assured a dedicated
design that thoroughly fulfills anatomical, physiological and engineering
constraints. RESULTS: System functionalities were demonstrated both in in-vitro
and ex-vivo conditions, reaching good results and promising outcomes in terms of
effectiveness and maneuverability. The retractor was successfully tested in an
animal model, carrying out a whole retraction procedure. CONCLUSION: The proposed
retraction system resulted to be intuitive, reliable, robust and easy to use,
representing a suitable device for MIS procedures.
PMID- 27616424
TI - The control of alternative splicing by SRSF1 in myelinated afferents contributes
to the development of neuropathic pain.
AB - Neuropathic pain results from neuroplasticity in nociceptive neuronal networks.
Here we demonstrate that control of alternative pre-mRNA splicing, through the
splice factor serine-arginine splice factor 1 (SRSF1), is integral to the
processing of nociceptive information in the spinal cord. Neuropathic pain
develops following a partial saphenous nerve ligation injury, at which time SRSF1
is activated in damaged myelinated primary afferent neurons, with minimal found
in small diameter (IB4 positive) dorsal root ganglia neurons. Serine arginine
protein kinase 1 (SRPK1) is the principal route of SRSF1 activation. Spinal SRPK1
inhibition attenuated SRSF1 activity, abolished neuropathic pain behaviors and
suppressed central sensitization. SRSF1 was principally expressed in large
diameter myelinated (NF200-rich) dorsal root ganglia sensory neurons and their
excitatory central terminals (vGLUT1+ve) within the dorsal horn of the lumbar
spinal cord. Expression of pro-nociceptive VEGF-Axxxa within the spinal cord was
increased after nerve injury, and this was prevented by SRPK1 inhibition.
Additionally, expression of anti-nociceptive VEGF-Axxxb isoforms was elevated,
and this was associated with reduced neuropathic pain behaviors. Inhibition of
VEGF receptor-2 signaling in the spinal cord attenuated behavioral nociceptive
responses to mechanical, heat and formalin stimuli, indicating that spinal VEGF
receptor-2 activation has potent pro-nociceptive actions. Furthermore,
intrathecal VEGF-A165a resulted in mechanical and heat hyperalgesia, whereas the
sister inhibitory isoform VEGF-A165b resulted in anti-nociception. These results
support a role for myelinated fiber pathways, and alternative pre-mRNA splicing
of factors such as VEGF-A in the spinal processing of neuropathic pain. They also
indicate that targeting pre-mRNA splicing at the spinal level could lead to a
novel target for analgesic development.
PMID- 27616429
TI - Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide
nanofibers.
AB - Atypical angiogenesis is one of the major symptoms of severe eye diseases,
including corneal neovascularization, and the complex nature of abnormal
vascularization requires targeted methods with high biocompatibility. The
targeting of VEGF is the most common approach for preventing angiogenesis, and
the LPPR peptide sequence is known to strongly inhibit VEGF activity by binding
to the VEGF receptor neuropilin-1. Here, the LPPR epitope is presented on a
peptide amphiphile nanofiber system to benefit from multivalency and increase the
anti-angiogenic function of the epitope. Peptide amphiphile nanofibers are
especially useful for ocular delivery applications due to their ability to remain
on the site of interest for extended periods of time, facilitating the long-term
presentation of bioactive sequences. Consequently, the LPPR sequence was
integrated into a self-assembled peptide amphiphile network to increase its
efficiency in the prevention of neovascularization. Anti-angiogenic effects of
the peptide nanofibers were investigated by using both in vitro and in vivo
models. LPPR-PA nanofibers inhibited endothelial cell proliferation, tube
formation, and migration to a greater extent than the soluble LPPR peptide in
vitro. In addition, the LPPR-PA nanofiber system led to the prevention of
vascular maturation and the regression of angiogenesis in a suture-induced
corneal angiogenesis model. These results show that the anti-angiogenic activity
exhibited by LPPR peptide nanofibers may be utilized as a promising approach for
the treatment of corneal angiogenesis.
PMID- 27616430
TI - Soy protein isolate as a nanocarrier for enhanced water dispersibility, stability
and bioaccessibility of beta-carotene.
AB - BACKGROUND: The incorporation of beta-carotene, one of the most common pigments
or bioactives, into food formulations has attracted increasing interest from the
food industry, due to its good nutrition and potential health effects. However,
it is poorly soluble and unstable in water, which greatly limits its applications
in foods. This work presented an effective approach to improve the water
dispersibility, stability and even bioaccessibility of beta-carotene, using soy
protein isolate (SPI) to perform as effective nanocarriers for this molecule.
RESULTS: The complexation with SPI remarkably improved the water dispersibility
and stability against heating and freeze-drying of beta-carotene. However, the
encapsulation efficiency and stability of beta-carotene in the nanocomplexes with
SPI were closely dependent on the applied beta-carotene-to-protein ratio, at
which the complexation occurred. The best improvement of stability was observed
at appropriate beta-carotene-to-protein ratios, e.g. 10-20 g kg-1 . The
complexation with beta-carotene mainly occurred on the surface of SPI
nanoparticles, through hydrophobic interactions. The complexation resulted in
inter-particle aggregation, in a concentration-dependent manner. Almost all of
the beta-carotene molecules in the nanocomplexes could be progressively released
into the aqueous phase. CONCLUSION: SPI exhibits a good potential to perform as a
nanocarrier for enhanced water dispersibility, stability and bioaccessibility of
beta-carotene. (c) 2016 Society of Chemical Industry.
PMID- 27616431
TI - Effects of fatty acid transport protein 1 on proliferation and differentiation of
porcine intramuscular preadipocytes.
AB - Fatty acid transport protein 1 (FATP1) plays an important role in the fatty acid
transmembrane transport and fat deposition. However, its role in porcine
intramuscular preadipocytes proliferation and differentiation remain poorly
understood. Here, we examined the effects of pFATP1 on porcine intramuscular
preadipocytes proliferation and differentiation. Overexpression of pFATP1 in
porcine intramuscular preadipocytes significantly promoted the proliferation of
porcine intramuscular preadipocytes, and also significantly upregulated the
expressions of peroxisome proliferator-activated receptor gamma, CCAAT enhancer
binding protein alpha, lipoprotein lipase, fatty acid synthetase and perilipin 1.
Moreover, overexpression of pFATP1 in porcine intramuscular preadipocytes
significantly increased fat accumulation and downregulated beta-catenin protein
expression. Overall, our results indicated that pFATP1 played an important role
in porcine intramuscular preadipocytes proliferation and differentiation, and it
might promote adipogenesis in porcine intramuscular preadipocytes by repressing
Wnt/beta-catenin signaling pathway.
PMID- 27616432
TI - Side strain in sport: a narrative review of pathomechanics, diagnosis, imaging
and management for the clinician.
AB - OBJECTIVES: To provide an overview of the published literature on epidemiology,
pathomechanics and risk factors for side strain injury in sport, complemented by
clinical perspectives of diagnosis and management strategies that are not covered
in the literature. DESIGN: Narrative review METHODS: A review of the literature
was completed with all studies on side strain up until October 2015 included. As
the studies were unable to be synthesised the findings were placed in a clinical
context. As there were no papers on the management of side strain a clinical
perspective from cricket was included. RESULTS: Literature on side strain in
sport is sparse with only nine papers dedicated to the injury. These comprise
epidemiology, case studies, small case series and clinical reviews on imaging,
injection and surgery. The epidemiology demonstrates that side strain is most
commonly associated with cricket and baseball. Side strain typically occurs
acutely mostly on the side contralateral to the dominant arm in athletes.
Diagnosis is clinical with consistent imaging features that typically demonstrate
a tear of the internal oblique from the lower ribs. Recovery periods can be
prolonged and recurrence may occur. There has been no research on the management
of side strain and the relationship between clinical assessment and imaging
findings and time to return to play or risk of recurrence. CONCLUSIONS: Side
strain injury is prevalent in cricket and baseball. Recovery is extended and
recurrence may occur. Incidence appears to be increasing. Knowledge on side
strain is limited.
PMID- 27616433
TI - Hippopotamus (H. amphibius) diet change indicates herbaceous plant encroachment
following megaherbivore population collapse.
AB - Megaherbivores (>1000 kg) are critical for ecosystem health and function, but
face population collapse and extinction globally. The future of these
megaherbivore-impoverished ecosystems is difficult to predict, though many
studies have demonstrated increasing representation of C3 woody plants. These
studies rely on direct observational data, however, and tools for assessing
decadal-scale changes in African ecology without observation are lacking. We use
isotopic records of historical common hippopotamus (Hippopotamus amphibius)
canines to quantify herbaceous vegetation change in Queen Elizabeth National
Park, Uganda following a period of civil unrest and poaching. This poaching event
led to population collapse of two threatened African megaherbivore species:
hippopotamus and African elephants (Loxodonta africana). Serial carbon isotope
ratios (delta(13)C) in canine enamel from individuals that lived between 1960
2000 indicated substantial increases in C3 herbaceous plants in their diet (<20%
C3 in the 1960s to 30-45% C3 in the 80s and 90s), supported by other
observational and ecological data. These data indicate megaherbivore loss results
in succession of both woody and herbaceous C3 vegetation and further reaching
effects, such as decreased grazing capacity and herbivore biodiversity in the
area. Given multiple lines of evidence, these individuals appear to accurately
capture herbaceous vegetation change in Mweya.
PMID- 27616434
TI - Rumination in dysphoric mothers negatively affects mother-infant interactions.
AB - BACKGROUND: Postnatal maternal depressive symptoms are consistently associated
with reduced quality of mother-infant interaction. However, there is little
research examining the role of maternal cognitive factors (e.g. rumination) in
the relationship between depressive symptoms and mother-infant interaction
quality. This study investigated the hypotheses that: dysphoric mothers would
demonstrate less sensitive behaviour towards their infants compared with
nondysphoric mothers; mothers induced to ruminate would be less sensitive towards
infants; rumination would moderate the relationship between maternal depressive
symptoms and maternal sensitivity and the impact of the rumination induction
would increase following a stressor (still face) task. METHOD: Mothers (N = 79;
39 dysphoric and 40 nondysphoric) and their infants were randomised to either a
rumination induction or a control condition. Maternal sensitivity in mother
infant interactions was assessed before and after the induction using the CARE
Index. In the second interaction task, mothers also completed the still-face
procedure as a stressor. RESULTS: Extending previous research, mixed measures
ANOVAs demonstrated that dysphoric mothers had reduced quality of interaction
with their infant compared with nondysphoric mothers and that mothers in the
rumination condition exhibited reduced sensitivity towards their infants relative
to mothers in the control condition. Further, maternal sensitivity worsened
further after the still-face procedure in the rumination condition, but not in
the control condition. CONCLUSIONS: This study suggests that the repetitive,
internal focus of a ruminative state is causally implicated in mother-infant
interaction quality, regardless of the level of depressive symptoms. This
research extends understanding of specific mechanisms involved in the quality of
the mother-infant relationship.
PMID- 27616435
TI - Palatal wound healing using a xenogeneic collagen matrix - histological outcomes
of a randomized controlled clinical trial.
AB - AIM: The aim of this study was to test whether or not a collagen matrix can
improve early wound healing compared to spontaneous healing based on histological
and immunohistologic analyses. METHODS: In 20 volunteers, 6 mm punch biopsies
were harvested at the palate. A xenogeneic collagen matrix (XCM) was sutured in
one site; the other one was left untreated (control). Biopsies with a diameter of
8 mm were subsequently obtained at 4, 8, 15 and 29 days and histological and
immunohistologic analyses were performed. RESULTS: At day 4, wound bed
keratinization amounted to 12.4 +/- 7.5% (control) and 18.0 +/- 10.2% (XCM). This
increased up to day 8 (19.7 +/- 25.5% control; 29.1 +/- 8.0% XCM) and reached
complete keratinization at day 15 in both groups. The quantitative analyses of
the superficial compartment measured an increase in the amount of granulation
tissue (32-88% control; 14-41% XCM) from day 4 to day 8. Angiogenesis was first
detected at 8 days. At day 29, the amount of connective tissue in all
compartments reached values similar to the native tissue at baseline.
CONCLUSIONS: The application of a XCM as a wound dressing on palatal wounds might
be beneficial in the early stages of wound healing. Further research with a
larger sample size is needed to confirm these results.
PMID- 27616436
TI - Impact of providing patients with copies of their medical correspondence: a
randomised controlled study.
AB - BACKGROUND: In Australia, correspondence is routinely sent to general
practitioners following a specialist consultation. Written communication is an
important way to enhance patient experiences and understanding, yet most patients
do not receive copies of their medical correspondence. AIMS: To determine whether
providing clinic correspondence and endoscopy reports to patients leads to
improved understanding, satisfaction or anxiety. METHODS: This is a prospective,
randomised controlled study conducted at an Australian tertiary hospital from
October 2013 to February 2015. New adult referrals to the general
gastroenterology clinic requiring an urgent endoscopic procedure were eligible
for the study. The intervention group received a copy of their clinic
correspondence and endoscopy report, while the control group received neither.
Participants completed questionnaires, including visual analogue scales and the
Hospital Anxiety and Depression Scale, at three time points. Primary outcomes
were patient understanding, anxiety and satisfaction. RESULTS: A total of 70
participants was included in the study. There was no reduction in anxiety levels
(P = 0.52), no increase in understanding (P = 0.73) or any increase in
satisfaction (P = 0.33) in participants receiving correspondence. However, 97% of
participants indicated that they wished to receive correspondence in the future,
and 94% of participants in the correspondence group reported that receiving
correspondence had helped them to understand their medical condition. CONCLUSION:
Patients wish to receive copies of their correspondence and feel it improves
their understanding of their medical condition. Although we were unable to
demonstrate a measurable reduction in anxiety, increase in understanding or
satisfaction, we recommend that patients be offered the choice of receiving
copies of their clinic correspondence and endoscopy reports.
PMID- 27616437
TI - A PCR-based survey of animal African trypanosomosis and selected piroplasm
parasites of cattle and goats in Zambia.
AB - We screened cattle and goats from the districts of Chama, Monze and Mumbwa in
Zambia for animal African trypanosomes, Babesia bigemina and Theileria parva
using PCRs; 38.1% of the samples tested positive for at least one of the parasite
species. The most common parasite was Trypanosoma vivax (19.8%). Its incidence
was significantly higher in goats than in cattle, (P<0.05). B. bigemina was found
in samples from all the three areas, making it the most widespread of the
parasites in Zambia. Among the tested samples, 12.0% of the positive samples were
mixed infections. There were significant differences in the infection rates of T.
vivax (Mumbwa had a significantly higher infection rate [39.6%, P<0.0001]), Th.
parva (Monze had the only cases [P<0.0004]) and B. bigemina (Monze had a
significantly higher infection rate [40.5%, P<0.0001]). According to the
hematocrit values, the packed cell volume (%) among the cattle with mixed
infections was significantly lower than that of the other cattle. The presence of
multiple parasite species and mixed infections among the Zambian cattle and goat
populations is of both clinical and economic importance to livestock farming. The
absence of trypanosomosis among the samples from Monze can be attributed to
tsetse eradication efforts that took place around Lake Kariba. This shows that
the prevention and control of these parasitic diseases can have a significant
impact on the disease status, which can translate directly into the improvement
of the livestock sector in Zambia.
PMID- 27616439
TI - The E3 ubiquitin ligase MARCH3 controls the endothelial barrier.
AB - Cell-cell contacts coordinate the endothelial barrier function in response to
external cues. To identify new mediators involved in cytokine-promoted
endothelial permeability, we screened a siRNA library targeting E3 ubiquitin
ligases. Here, we report that silencing of the late endosome/lysosomal membrane
associated RING-CH-3 (MARCH3) enzyme protects the endothelial barrier.
Furthermore, transcriptome analysis unmasked the upregulation of the tight
junction-encoding gene occludin (OCLN) in MARCH3-depleted cells. Indeed, MARCH3
silencing results in the strengthening of cell-cell contacts, as evidenced by the
accumulation of junctional proteins. From a molecular standpoint, the FoxO1
forkhead transcription repressor was inactivated in the absence of MARCH3. This
provides a possible molecular link between MARCH3 and the signaling pathway
involved in regulating the expression of junctional proteins and barrier
integrity.
PMID- 27616438
TI - Evaluation of the information given to patients undergoing head and neck cancer
surgery using the EORTC QLQ-INFO25 questionnaire: A prospective multicentric
study.
AB - AIM: Providing head and neck cancer patients with adequate information is
essential to their confidence and satisfaction regarding medical care. The aims
of this study were to evaluate patient perceptions of the information received,
the predictive factors of such perceptions and their potential correlation with
patient quality of life (QoL). METHODS: We conducted a prospective multicentric
study using the European Organization for Research and Treatment of Cancer
(EORTC) QLQ-INFO25 and QLQ-C30 questionnaires before and after surgery. RESULTS:
This study enrolled 200 patients, 149 men and 51 women, mean age 63.5 +/- 10.3
years. Before and after treatment, global QLQ-INFO25 scores were 39.3 and 42.5,
respectively, whereas satisfaction with the information received scores were 69.9
and 58.1, respectively. Regarding EORTC QLQ-INFO25 scores, between the pre- and
post-treatment periods, we observed a significant increase in three scales/items
(information about other services, information about different places of care and
information about things you can do to help yourself) and a significant decrease
in two scales/items (satisfaction with the information received and overall the
information has been helpful). Before and after treatment, global QoL scores were
62.7 and 61.0, respectively. Overall, we found low correlations between QLQ
INFO25 and QLQ-C30 scores. Patient age and education level, centre of care,
tumour site and treatment characteristics had a significant impact on QLQ-INFO25
scores. CONCLUSION: Perceived information was satisfactory in the perioperative
period for head and neck cancer patients. Several demographic and clinical
factors were identified as significant predictors of QLQ-INFO25 scores.
PMID- 27616441
TI - Coupling between ATP hydrolysis and protein conformational change in maltose
transporter.
AB - As the intracellular part of maltose transporter, MalK dimer utilizes the energy
of ATP hydrolysis to drive protein conformational change, which then facilitates
substrate transport. Free energy evaluation of the complete conformational change
before and after ATP hydrolysis is helpful to elucidate the mechanism of chemical
to-mechanical energy conversion in MalK dimer, but is lacking in previous
studies. In this work, we used molecular dynamics simulations to investigate the
structural transition of MalK dimer among closed, semi-open and open states. We
observed spontaneous structural transition from closed to open state in the ADP
bound system and partial closure of MalK dimer from the semi-open state in the
ATP-bound system. Subsequently, we calculated the reaction pathways connecting
the closed and open states for the ATP- and ADP-bound systems and evaluated the
free energy profiles along the paths. Our results suggested that the closed state
is stable in the presence of ATP but is markedly destabilized when ATP is
hydrolyzed to ADP, which thus explains the coupling between ATP hydrolysis and
protein conformational change of MalK dimer in thermodynamics. Proteins 2017;
85:207-220. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616440
TI - [Spinal sinovial cysts: Surgical treatment and clinical outcomes in a series of
18 cases].
AB - OBJECT: A series of 18 patients with symptomatic synovial cysts was analysed from
May 2009 to November 2013. Different approaches were performed for their removal.
MATERIAL AND METHODS: The study included 18 patients, 8 men and 10 women, aged
between 50 and 77 years. An analysis was made of the variables including age,
gender, symptoms, imaging studies, histopathology, surgery, follow-up,
complications, and clinical outcome. RESULTS: An articular synovial cyst was
diagnosed in 17 cases, and a ganglion in one cases. The most common symptom was
back pain with radiculopathy (94%). Motor deficits occurred in 4 cases (22%), and
1 case (5%) presented with urinary incontinence. The most common level was L4- L5
(67%), with one atypical case observed in the D12 -L1 location. Hemi-laminectomy
was performed in 14 cases, with 9 of them having an interspinous spacer (ISP)
device inserted. A laminectomy with a fusion procedure was performed in 3
patients and 1 patient had a bilateral decompression using a unilateral approach.
The patients were followed-up for between 6 months to 2 years. CONCLUSIONS:
Synovial cysts are a cause of radiculopathy/neurogenic claudication. Spinal cysts
are commonly found at the L4-L5 level. MRI is the tool of choice for diagnosis.
The most common symptom was back pain with radiculopathy. Synovial cysts
resistant to conservative therapy should be treated surgically. In our series,
surgical resection of symptomatic juxtafacet cysts showed a good clinical
outcome, but the optimal approach for patients with juxtafacet cysts remains
unclear.
PMID- 27616442
TI - Effect of Condensed Tannin Profile on Wheat Flour Dough Rheology.
AB - Proanthocyanidins (PA) cross-link proteins and could expand wheat gluten
functionality; however, how the PA MW or gluten profile affect these interactions
is unknown. Effect of PA MW profile (sorghum versus grape seed PA) on dough
rheology of high versus low insoluble polymeric protein (IPP) wheat flour was
evaluated using mixograph, large (TA.XT2i) and small (HAAKE Rheostress 6000)
deformation rheometry. Sorghum PA (93% polymeric) more effectively (p < 0.05)
strengthened both glutens than grape seed PA (45% polymeric), without reducing
gluten extensibility. These effects were higher in low IPP (weak gluten) flour,
e.g., sorghum PA doubled IPP, increased mix time by 75%, dough elasticity by 82%,
and peak angle by 17 degrees versus control. Grape seed PA increased IPP by 75%
and elasticity by 36%, but reduced peak angle by 15 degrees , indicating reduced
mixing tolerance. Sorghum PA, but not grape seed PA, increased (p < 0.05) all
above parameters in high IPP dough. Polymeric PA more effectively strengthened
gluten than oligomeric PA, likely via more efficient protein cross-linking to
overcome strong antioxidant effect of PA. High MW PA may be useful natural gluten
strengtheners for diverse applications.
PMID- 27616443
TI - Clostridium difficile presence in Spanish and Belgian hospitals.
AB - Clostridium difficile is recognised worldwide as the main cause of infectious
bacterial antibiotic-associated diarrhoea in hospitals and other healthcare
settings. The aim of this study was to first survey C. difficile prevalence
during the summer of 2014 at the Central University Hospital of Asturias (Spain).
By typing the isolates obtained, it was then possible to compare the ribotype
distribution at the Spanish hospital with results from the St Luc University
Hospital in Belgium over the same period. The prevalence of positive cases
reported in Spain and Belgium was 12.3% and 9.3% respectively. The main PCR
ribotypes previously described in Europe were found in both hospitals, including
078, 014, 012, 020 and 002. In the Spanish hospital, most of the C. difficile
positive samples were referred from oncology, acute care and general medicine
services. In the Belgian hospital the majority of positive samples were referred
from the paediatric service. However, a high percentage of isolates from this
service were non-toxigenic. This study finds that the presence and detection of
C. difficile in paediatric and oncology services requires further investigation.
PMID- 27616444
TI - MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary
tuberculosis: A preliminary study.
AB - In our study, we aimed to profile a panel microRNAs (miRNAs) as potential
biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to
illuminate the molecular mechanisms in the development of PTB. Firstly, gene
expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and
quantile-adjusted conditional maximum likelihood method was utilized to identify
statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)
infected individuals and healthy subjects. Furthermore, in order to assess the
performance of our methodology, random forest (RF) classification model was
utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC)
using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation
was repeated 50 times to explore the best miRNAs. In order to learn more about
the differentially-expressed miRNAs, the target genes of differentially-expressed
miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis
(IPA) was used to screen out biological pathways where target genes were
involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold
quantile average across all samples were required. Based on the differential
expression analysis, 38 differentially expressed miRNAs were identified when the
significance was set as false discovery rate (FDR) < 0.01. Among the top 10
differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976,
showing a good performance between PTB and control groups. Similarly, miRNA-449a,
miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947,
0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and
miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132
might be important in the progression of PTB and thereby, might present potential
signatures for diagnosis of PTB.
PMID- 27616445
TI - Species diversity and molecular characterization of nontuberculous mycobacteria
in hospital water system of a developing country, Iran.
AB - BACKGROUND: Hospital environment is of crucial importance in cross-transmission
of opportunistic pathogens to the patients. Nontuberculous mycobacteria have the
remarkable capability to withstand the adverse condition of hospital environments
and pose a potential threat to the health of patients. The current study aimed to
assess the frequency and diversity of mycobacteria in hospital water of a
developing country using a combination of conventional and molecular methods.
METHODS: A total of 148 hospital water samples collected from 38 hospitals were
analyzed for the presence of mycobacteria using standard protocols for isolation
and characterization of the isolates. The conventional tests were used for
preliminary identification and Runyon's classification, the PCR amplification of
hsp65 gene and sequence analysis of 16S rRNA were applied for the genus and
species identification. RESULTS: A total of 71 [48%] isolates including 30
rapidly growing and 41 slowly growing mycobacteria were recovered. The three most
prevalent species were M. lentiflavum, 28.2%, M. paragordonae, 21.1%, and M.
fredriksbergense, 9.8%, followed by M. simiae and M. novocastrense, 7%, M.
canariasense and M. cookii like, 5.6%, M. setense, 4.2%, M. fortuitum and M.
gordonae, 2.8%, and the single isolates of M. austroafricanum, M. massiliense, M.
obuense, and M. phocaicum like. CONCLUSION: The results of our study show that
the hospital water resources, drinking or non-drinking can be the reservoir of a
diverse range of mycobacteria. This reaffirms the fact that these organisms due
to intrinsic resistance to common antiseptic and disinfectant solutions persist
in hospitals and create a threat to the patient's health and in particular to
those that suffer from weakness of immunity.
PMID- 27616447
TI - Efficient nonarterialized mouse liver transplantation using 3-dimensional-printed
instruments.
AB - Because of the wide availability of genetically modified animals, mouse
orthotopic liver transplantation is often preferred over rat liver
transplantation. We present a simplified mouse liver transplantation technique
and compare transplantation outcomes with versus without hepatic artery
anastomosis. Instruments for liver implantation were designed and printed with a
3-dimensional (3D) printer. The suprahepatic vena cava anastomosis was performed
with a 10-0 running suture. The vena porta and infrahepatic vena cava were joined
on extraluminal cuffs, using the 3D-printed device for spatial alignment and
stabilization. The hepatic artery was reconstructed in half of the recipients
using intraluminal stents. Liver function tests (3, 7, and 28 days) and histology
(7 and 28 days) were assessed after transplantation. We performed 22 consecutive
syngeneic C57BL/6 mouse orthotopic liver transplantations. The median portal
clamping time was 12.5 +/- 1.5 minutes. The survival rate at 4 weeks was 100% for
both arterialized and nonarterialized recipients (n = 7, 4 recipients of each
group being killed for early histology at day 7). Liver function tests at 3, 7,
and 28 days were similar between arterialized versus nonarterialized groups.
Liver parenchyma demonstrated only irrelevant abnormalities in both groups. The
proposed device allows for a shorter clamping time compared with the published
literature. Using this technique, the artery does not need to be anastomosed,
with no impact on graft and recipient outcomes. The device is available for 3D
printing. Liver Transplantation 22 1688-1696 2016 AASLD.
PMID- 27616446
TI - The YfcO fimbriae gene enhances adherence and colonization abilities of avian
pathogenic Escherichia coli in vivo and in vitro.
AB - Chaperone-usher (CU) fimbriae, which are adhesive surface organelles found in
many Gram-negative bacteria, mediate tissue tropism through the interaction of
fimbrial adhesins with specific receptors expressed on the host cell surface. A
CU fimbrial gene yfcO, was identified in avian pathogenic E. coli (APEC) strain
DE205B via gene functional analysis. In this study, yfcO was found in 13.41%
(11/82) of E. coli strains, including phylogenetic groups A, B1, B2 and D, with
the highest percentage in group B2. The expression of yfcO in biofilm forming
bacteria was significantly higher (P < 0.05) than that in the planktonic
bacteria. A yfcO deletion mutant was constructed, and adherence to DF-1 chicken
embryo fibroblast cells was analyzed in vitro. Compared to the wild-type (WT),
adherence of the mutant to DF-1 cells was significantly decreased (P < 0.01). The
mutant bacterial loads in the heart, brain and liver were significantly lower (P
< 0.05) than those of the WT strain. Resistance of the mutant to acidic (acetic,
pH 4.0, 20 min) and high osmolarity (2.5 M NaCl, 1 h) stress conditions decreased
by 51.28% (P < 0.001) and 80.34% (P < 0.01), respectively. These results suggest
that yfcO contributes to APEC virulence through bacterial adherence to host
tissues.
PMID- 27616448
TI - Quenched Magnon excitations by oxygen sublattice reconstruction in
(SrCuO2)n/(SrTiO3)2 superlattices.
AB - The recently discovered structural reconstruction in the cuprate superlattice
(SrCuO2)n/(SrTiO3)2 has been investigated across the critical value of n = 5
using resonant inelastic x-ray scattering (RIXS). We find that at the critical
value of n, the cuprate layer remains largely in the bulk-like two-dimensional
structure with a minority of Cu plaquettes being reconstructed. The partial
reconstruction leads to quenching of the magnons starting at the Gamma-point due
to the minority plaquettes acting as scattering points. Although comparable in
relative abundance, the doped charge impurities in electron-doped cuprate
superconductors do not show this quenching of magnetic excitations.
PMID- 27616449
TI - Corrigendum: Modeling crowdsourcing as collective problem solving.
PMID- 27616450
TI - Sympathetic Nerve Activity Efferent Drive and Beta-Blocker Treatment - Effect of
Interaction in Systolic Heart Failure.
AB - BACKGROUND: Although both beta-blocker dose (BBD) and sympathetic activity
efferent drive are associated with prognosis in chronic heart failure (HF),
little is known about the prognostic value of the interaction between them.
METHODS AND RESULTS: Potential prognostic variables including resting muscle
sympathetic nerve activity (MSNA) were investigated in 133 patients with HF
(ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent
doses of carvedilol. Primary cardiovascular endpoints included cardiovascular
death and HF hospitalization. Predictors for outcomes were assessed on
univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months
after MSNA measurement in 102 patients. During the 1,419+/-824-day follow-up
period, 24 patients died (sudden death, n=10; progressive HF, n=14). On
multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01)
and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of
cardiovascular events. Patients were divided into higher MSNA (>=64 bursts/100
beats) and lower MSNA groups. Although lower BBD remained an independent
predictor in patients with higher MSNA, BBD was not statistically significant in
patients with lower MSNA on univariate analysis. Additionally, there was a lower
EF change in patients with lower BBD and higher MSNA. CONCLUSIONS: Higher BBD
might be necessary to avoid cardiovascular events in HF patients with central
sympathetic overactivation. (Circ J 2016; 80: 2149-2154).
PMID- 27616451
TI - Role of the gut microbiota in host appetite control: bacterial growth to animal
feeding behaviour.
AB - The life of all animals is dominated by alternating feelings of hunger and
satiety - the main involuntary motivations for feeding-related behaviour. Gut
bacteria depend fully on their host for providing the nutrients necessary for
their growth. The intrinsic ability of bacteria to regulate their growth and to
maintain their population within the gut suggests that gut bacteria can interfere
with molecular pathways controlling energy balance in the host. The current model
of appetite control is based mainly on gut-brain signalling and the animal's own
needs to maintain energy homeostasis; an alternative model might also involve
bacteria-host communications. Several bacterial components and metabolites have
been shown to stimulate intestinal satiety pathways; at the same time, their
production depends on bacterial growth cycles. This short-term bacterial growth
linked modulation of intestinal satiety can be coupled with long-term regulation
of appetite, controlled by the neuropeptidergic circuitry in the hypothalamus.
Indeed, several bacterial products are detected in the systemic circulation,
which might act directly on hypothalamic neurons. This Review analyses the data
relevant to possible involvement of the gut bacteria in the regulation of host
appetite and proposes an integrative homeostatic model of appetite control that
includes energy needs of both the host and its gut bacteria.
PMID- 27616452
TI - Brown adipose tissue as a secretory organ.
AB - Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and
experimental studies have associated BAT activity with protection against obesity
and metabolic diseases, such as type 2 diabetes mellitus and dyslipidaemia.
Active BAT is present in adult humans and its activity is impaired in patients
with obesity. The ability of BAT to protect against chronic metabolic disease has
traditionally been attributed to its capacity to utilize glucose and lipids for
thermogenesis. However, BAT might also have a secretory role, which could
contribute to the systemic consequences of BAT activity. Several BAT-derived
molecules that act in a paracrine or autocrine manner have been identified. Most
of these factors promote hypertrophy and hyperplasia of BAT, vascularization,
innervation and blood flow, processes that are all associated with BAT
recruitment when thermogenic activity is enhanced. Additionally, BAT can release
regulatory molecules that act on other tissues and organs. This secretory
capacity of BAT is thought to be involved in the beneficial effects of BAT
transplantation in rodents. Fibroblast growth factor 21, IL-6 and neuregulin 4
are among the first BAT-derived endocrine factors to be identified. In this
Review, we discuss the current understanding of the regulatory molecules (the so
called brown adipokines or batokines) that are released by BAT that influence
systemic metabolism and convey the beneficial metabolic effects of BAT
activation. The identification of such adipokines might also direct drug
discovery approaches for managing obesity and its associated chronic metabolic
diseases.
PMID- 27616453
TI - The phytopathogenic virulent effector protein RipI induces apoptosis in budding
yeast Saccharomyces cerevisiae.
AB - Virulent protein toxins secreted by the bacterial pathogens can cause
cytotoxicity by various molecular mechanisms to combat host cell defense. On the
other hand, these proteins can also be used as probes to investigate the defense
pathway of host innate immunity. Ralstonia solanacearum, one of the most virulent
bacterial phytopathogens, translocates more than 70 effector proteins via type
III secretion system during infection. Here, we characterized the cytotoxicity of
effector RipI in budding yeast Saccharomyce scerevisiae, an alternative host
model. We found that over-expression of RipI resulted in severe growth defect and
arginine (R) 117 within the predicted integrase motif was required for inhibition
of yeast growth. The phenotype of death manifested the hallmarks of apoptosis.
Our data also revealed that RipI-induced apoptosis was independent of Yca1 and
mitochondria-mediated apoptotic pathways because Deltayca1 and Deltaaif1 were
both sensitive to RipI as compared with the wild type. We further demonstrated
that RipI was localized in the yeast nucleus and the N-terminal 1-174aa was
required for the localization. High-throughput RNA sequencing analysis showed
that upon RipI over-expression, 101 unigenes of yeast ribosome presented lower
expression level, and 42 GO classes related to the nucleus or recombination were
enriched with differential expression levels. Taken together, our data showed
that a nuclear-targeting effector RipI triggers yeast apoptosis, potentially
dependent on its integrase function. Our results also provided an alternative
strategy to dissect the signaling pathway of cytotoxicity induced by the protein
toxins.
PMID- 27616455
TI - Genus Calliophis of Asiatic coral snakes: A deficiency of venom cross-reactivity
and neutralization against seven regional elapid antivenoms.
AB - Venoms of Calliophis bivirgata and Calliophis intestinalis exhibited moderate
binding activities toward Neuro Bivalent Antivenom (Taiwan) but not the other six
elapid monovalent or bivalent antivenoms available in the region. All antivenoms
failed to neutralize C. bivirgata venom lethality in mice. The findings indicate
the need to validate antivenom cross-reactivity with in vivo cross
neutralization, and imply that distinct antigens of Calliophis venoms should be
incorporated in the production of a pan-regional poly-specific antivenom.
PMID- 27616454
TI - Antiproliferative activity and chemical composition of the venom from the
Amazonian toad Rhinella marina (Anura: Bufonidae).
AB - Little is known on the composition of Peruvian Amazon toad venoms. The large toad
Rhinella marina is common in the cleared tropical forests of the Iquitos region
and is regarded as poisonous. The venom from two different populations of R.
marina was collected in the Departamento de Loreto, Peru. The samples were
assessed for antiproliferative effect and composition. Some 29 compounds were
identified or tentatively identified from the venom by spectroscopic and
spectrometric means. The main free bufadienolide was marinobufagin 7 while
marinobufotoxin 15 and bufalitoxin 9 were the main bufadienolide argininyl diacid
derivatives. The alkaloids dehydrobufotenin 28 and bufotenidin 29 were present in
both venoms. The main difference in the venoms was the relative ratio of
argininyl diacids from bufadienolides to free bufadienolides. The argininyl
diacids included derivatives from bufalin, marinobufagin, telocinobufagin,
hellebrigenin, resibufogenin and bufotalinin. Four compounds, including
undecadienoyl aginine 6 and three argininyl diacids from bufadienolides were
tentatively identified for the first time in the samples. The venom showed a
strong antiproliferative effect towards MRC-5 normal human lung fibroblasts
(0.063-0.247 MUg/mL), AGS human gastric adenocarcinoma cells (0.076-0.272
MUg/mL), SK-MES-1 human lung cancer cells (0.154-0.296 MUg/mL), J82 human bladder
carcinoma cells (0.169-0.212 MUg/mL), and HL-60 human promyelocytic leukemia
(0.071-0.283 MUg/mL). The antiproliferative effect is mediated by ROS production
and cell cycle arrest in human breast cancer cells (MCF7 and MDA-MB-231). This is
the first report on the composition of R. marina venom from the Peruvian Amazon
pointing out the need to include different venom samples to get a better picture
from the activity and composition of South American toad defense substances.
PMID- 27616456
TI - Synthesis, in vitro evaluation and molecular docking studies of novel coumarin
isatin derivatives as alpha-glucosidase inhibitors.
AB - This study synthesized a series of novel coumarin-isatin derivatives and
evaluated them for alpha-glucosidase inhibitory activity. The majority of the
screened compounds exhibited excellent inhibition activities with IC50 values of
2.56 +/- 0.08-268.79 +/- 3.04 MUm, when compared to acarbose. Among the newly
derivatives, compound 5p was found to be the most active compound in the library
of coumarin-isatin derivatives. Furthermore, enzyme kinetic studies showed that
compound 5p is a non-competitive inhibitor with a Ki of 2.14 MUm. Molecular
docking analysis revealed the existence of hydrophobic and hydrogen interactions
between compound 5p and the active site of alpha-glucosidase. Our results
indicate that coumarin-isatin derivatives as a new class of alpha-glucosidase
inhibitors.
PMID- 27616457
TI - Structural features and activity of Brazzein and its mutants upon substitution of
a surfaced exposed alanine.
AB - Brazzein (Brz) is a member of sweet-tasting protein containing four disulfide
bonds. It was reported as a compact and heat-resistant protein. Here, we have
used site-directed mutagenesis and replaced a surface-exposed alanine with
aspartic acid (A19D mutant), lysine (A19K mutant) and glycine (A19G mutant).
Activity comparisons of wild-type (WT) and mutants using taste panel test
procedure showed that A19G variant has the same activity as WT protein. However,
introduction of a positive charge in A19K mutant led to significant increase in
Brz's sweetness, while A19D has reduced sweetness compared to WT protein. Docking
studies showed that mutation at position 19 results in slight chain mobility of
protein at the binding surface and changing the patterns of interactions toward
more effective binding of E9K variant in the concave surface of sweet taste
receptor. Far-UV CD data spectra have a characteristic shape of beta structure
for all variants, however different magnitudes of spectra suggest that beta-sheet
structure in WT and A19G is more stable than that of A19D and A19K. Equilibrium
unfolding studies with fluorescence spectroscopy and using urea and dithiothritol
(DTT) as chemical denaturants indicates that A19G mutant gains more stability
against urea denaturation; while conformational stability of A19D and A19K
decreases when compared with WT and A19G variants. We concluded that the positive
charge at the surface of protein is important factor responsible for the
interaction of protein with the human sweet receptor and Ala19 can be considered
as a key region for investigating the mechanism of the interaction of Brz with
corresponding receptor.
PMID- 27616460
TI - Palladium-Catalyzed Cascade Arene/Alkyne Annulation: Synthesis of Fluorene
Benzoxazine Derivatives.
AB - A palladium-catalyzed cascade arene/alkyne annulation reaction for the synthesis
of fluorene-benzoxazine derivatives is developed. This transformation involves a
6-exo-dig cyclization, a 1,3-oxazine vinylpalladium intermediate, and a C-H bond
activation.
PMID- 27616458
TI - The magnitude of cytokine production by stimulated CD56+ cells is associated with
early stages of systemic sclerosis.
AB - Immune activation is a hallmark of systemic sclerosis (SSc). However, the
immunological alterations that occur in preclinical and non-fibrotic SSc and that
differentiate these subjects from those with primary Raynaud's phenomenon (PRP)
or healthy controls (HC) are poorly defined. We isolated CD56+ (NK/NKT-like)
cells from HC, patients with PRP, early SSc (EaSSc) and definite SSc without skin
or lung fibrosis. Cytokine production upon different activating stimuli was
measured via a multiplex immuno assay. Clearly discriminative patterns among the
different stages of SSc were most markedly observed after TLR1/2 stimulation,
with increased IL-6, TNF-alpha and MIP-1alpha/CCL3 production in definite SSc
patients as compared to HC and/or PRP. Initial alterations were observed in EaSSc
patients with an intermediate secretion pattern between HC/PRP and definite SSc.
CD56+ cells from patients at different stages of SSc differentially respond to
TLR stimulation, highlighting the relevance of natural immunity in the
developmental and pre-fibrotic SSc.
PMID- 27616459
TI - Half-metallicity and ferromagnetism in penta-AlN2 nanostructure.
AB - We have performed a detailed first-principles study of the penta-AlN2
nanostructure in the Cairo pentagonal tiling geometry, which is dynamically
stable due to the absence of imaginary mode in the calculated phonon spectrum.
The formation energy and the fragment cohesive energy analyses, the molecular
dynamics simulations, and the mechanical property studies also support the
structural stability. It could withstand the temperature as high as 1400 K and
sustain the strain up to 16.1% against structural collapse. The slightly buckled
penta-AlN2 is found to be a ferromagnetic semiconductor. The strain of ~9% could
drive the structural transition from the buckled to the planar. Interestingly,
the strain of >7% would change the conducting properties to show half-metallic
characters. Furthermore, it could be also used to continuously enhance the
magnetic coupling strength, rendering penta-AlN2 as a robust ferromagnetic
material. These studies shed light on the possibilities in synthesizing penta
AlN2 and present many unique properties, which are worth of further studying on
both theory and experiment.
PMID- 27616461
TI - Multiple unusual lung etiologies in a child with acute lymphocytic leukemia.
AB - Granulomatous lung disease is a rare and perplexing differential in pediatrics.
Pulmonary Cryptococcus falls into the differential but is not high on the list,
particularly in a non-AIDS patient. Methotrexate (MTX) is a commonly used agent
for chemotherapy in oncology and has been documented to cause lung injury in both
patients with rheumatologic and oncologic diseases. Our patient had chronic cough
and then developed an opportunistic infection resulting in respiratory failure.
Lung biopsy showed two underlying unusual diagnoses: MTX lung injury and
cryptococcal pneumonia. His case is presented with particular attention to his
prolonged road to diagnosis.
PMID- 27616462
TI - The impact of smoking cues in antismoking messages among intermittent and light
smokers.
AB - OBJECTIVE: Based on the Limited Capacity Model of Motivated Mediated Message
Processing, this study explored the effects of smoking cues in antismoking Public
Service Announcements (PSAs) on message processing among intermittent/light
smokers and nonsmokers. METHOD: A 2 (smoking cues: present vs. absent) * 2
(smoking status: smokers vs. nonsmokers) mixed experimental design was conducted.
Self-report measures and two physiological measures including skin conductance
and heart rate were examined. RESULTS: Messages with smoking cues generated
higher levels of arousal (F = 4.57, p = .04), attention (F = 2.51, p = .04),
positive message evaluation (F = 28.70, p < .001) and less intent to smoke (F =
26.60, p < .001). Intermittent and light smokers had much stronger reactions to
messages containing tobacco-related visuals, including arousal (F = 4.10, p =
.04), perceived ad effectiveness (F = 9.24, p = .03) and intent to smoke (F =
22.98, p < .001). IMPLICATION: The antismoking arguments may have suppressed cue
induced smoking urges, which dampened negative persuasion outcomes. Limitations
included the restricted generalisability and the focus on short-term effect.
Future research may use a random sample of PSAs with a general population.
PMID- 27616463
TI - Local and Circulating Endothelial Cells Undergo Endothelial to Mesenchymal
Transition (EndMT) in Response to Musculoskeletal Injury.
AB - Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of
aberrant wound healing conditions. However, unambiguous evidence of EndMT has
been elusive due to limitations of in vitro experimental designs and animal
models. In vitro experiments cannot account for the myriad ligands and cells
which regulate differentiation, and in vivo tissue injury models may induce
lineage-independent endothelial marker expression in mesenchymal cells. By using
an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior
to injury, we demonstrate that musculoskeletal injury induces expression of CD31,
VeCadherin, or Tie2 in mesenchymal cells. VeCadherin and Tie2 were expressed in
non-endothelial cells (CD31-) present in marrow from uninjured adult mice,
thereby limiting the specificity of these markers in inducible models (e.g.
VeCadherin- or Tie2-creERT). However, cell transplantation assays confirmed that
endothelial cells (DeltaVeCadherin/CD31+/CD45-) isolated from uninjured hindlimb
muscle tissue undergo in vivo EndMT when transplanted directly into the wound
without intervening cell culture using PDGFRalpha, Osterix (OSX), SOX9, and
Aggrecan (ACAN) as mesenchymal markers. These in vivo findings support EndMT in
the presence of myriad ligands and cell types, using cell transplantation assays
which can be applied for other pathologies implicated in EndMT including tissue
fibrosis and atherosclerosis. Additionally, endothelial cell recruitment and
trafficking are potential therapeutic targets to prevent EndMT.
PMID- 27616464
TI - Comparison of body mass index with abdominal obesity for identifying elevated
blood pressure in children and adolescents: The SNEC study.
AB - Body mass index (BMI) and waist circumference (WC) are two common ways to measure
obesity. There is a debate, however, about which of these two measures are more
closely associated with elevated blood pressure (BP). The aim of this study is to
investigate the prevalence of obesity and whether BMI and WC is better associated
with elevated BP in children and adolescents. A representative sample of 8613
Chinese youth aged 7-17 years from seven cities in Northeastern China was
selected and measurements of height, weight, WC, BP were taken from 2012 to 2013.
The average age of the children was 11.3+/-2.3years. The prevalence of
overweight/obese and abdominal obesity in the subjects was 35% and 44.8%,
respectively. We found that both BMI and WC were significantly associated with
elevated BP. An increase of 1kgm-2 in BMI was associated with a 1.10 (1.08-1.12,
95% CI) increased risk of an elevated BP diagnosis in boys, and a 1.14 (1.11
1.16, 95% CI) increased risk in girls. Meanwhile, a 1cm increase in WC correlated
with a 1.03 (1.02-1.04, 95% CI) and a 1.05 (1.04-1.06, 95% CI) increased risk of
higher BP in boys and girls, respectively. Compared to the normal-weight youth,
subjects with elevated BMI (BMI>85th) had higher risk of elevated BP (OR: 2.42,
95% CI: 2.13-2.75) than that of in elevated WC participants (OR: 2.00, 95% CI:
1.77-2.27). Therefore, BMI may associate better with elevated BP than WC in
Chinese youth in our Seven Northeastern Cities study.
PMID- 27616465
TI - Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines
Benzo[e][1,2,3]oxathiazine 2,2-Dioxides Catalyzed by Cinchona Alkaloid-based
Primary Amines.
AB - Aryl ketones represent problematic substrates for asymmetric Mannich reactions
due to a large steric hindrance exhibited by such compound species. A highly
enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine
benzo[e][1,2,3]oxathiazine 2,2-dioxides could be successfully carried out
utilizing a combination of cinchona alkaloid-derived primary amines with
trifluoroacetic acid (TFA); the primary amines feature a superior catalytic
efficacy over secondary amines with a variety of sterically hindered carbonyl
compounds as substrates. The reaction proceeded well with various cyclic imines
in 89-97 % ee and with various aryl methyl ketones in 85-98 % ee. Moreover, the
aryl carbonyl of a Mannich product could be transformed to ketoxime, which
further undergoes a Beckmann rearrangement to produce an amide compound while
maintaining enantioselectivity.
PMID- 27616466
TI - Long-Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment
Using a Microspheres/Carrier System.
AB - Core-shell polymer microspheres with poly(d,l-lactic-co-glycolic acid) core and
poly(l-lactic acid) (PLLA) shell are developed for the long-term subconjunctival
release of brimonidine tartrate (BT) in order to reduce intraocular pressure
(IOP) in the treatment of glaucoma. The PLLA-rich shell acts as a diffusion
barrier, enabling linear release of BT over an extended period of 40 d. The
microspheres are encased in a porous non-degradable methacrylate-based carrier
for ease of subconjunctival implantation in a glaucoma-induced rabbit model. In
vivo release of BT from the microspheres/carrier system has enabled a
significant, immediate IOP reduction of 20 mmHg, which is sustained for 55 d.
Long-term IOP reduction may be maintained by periodic replacement of the
microspheres/carrier system.
PMID- 27616467
TI - An easy-to-use and versatile method for building cell-laden microfibres.
AB - Fibre-shaped materials are useful for creating different functional three
dimensional (3D) structures that could mimic complex tissues. Several methods
(e.g. extrusion, laminar flow or electrospinning) have been proposed for building
hydrogel microfibres, with distinctive cell types and with different degrees of
complexity. However, these methods require numerous protocol adaptations in order
to achieve fibre fabricating and lack the ability to control microfibre
alignment. Here, we present a simple method for the production of microfibers,
based on a core shell approach, composed of calcium alginate and type I collagen.
The process presented here allows the removal of the calcium alginate shell,
after only 24 hours of culture, leading to stable and reproducible fibre shaped
cellular constructs. With time of culture cells show to distribute preferentially
to the surface of the fibre and display a uniform cellular orientation. Moreover,
when cultured inside the fibres, murine bone marrow mesenchymal stem cells show
the capacity to differentiate towards the osteoblastic lineage, under non
osteoinductive culture conditions. This work establishes a novel method for
cellular fibre fabrication that due to its inherent simplicity can be easily
upscaled and applied to other cell types.
PMID- 27616468
TI - Tangeretin attenuates cisplatin-induced renal injury in rats: Impact on the
inflammatory cascade and oxidative perturbations.
AB - BACKGROUND: Despite the efficacy of cisplatin as a chemotherapeutic agent against
various cancers, its clinical utility is limited by serious adverse reactions
including nephrotoxicity. AIM: The current study aims to investigate the
protective potential of tangeretin, a citrus flavone with marked antioxidant
actions, against cisplatin-induced renal injury in rats. METHODS: Tangeretin was
administered at 50 and 100 mg/kg p.o. for 1 week starting one day before
cisplatin (7.5 mg/kg i.p.) injection. Likewise, silymarin was administered at 100
mg/kg orally. Renal function tests, histopathology, oxidative stress and
inflammatory events were investigated. RESULTS: Tangeretin mitigated the
increased levels of serum creatinine, blood urea nitrogen and histopathologic
alterations evoked by cisplatin. It alleviated renal oxidative stress due to
cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with
concomitant enhancement of GSH and GPx. Tangeretin also suppressed the
upregulated inflammatory response seen with cisplatin treatment by downregulation
of activated NF-kappaB p65 protein expression together with its downstream
effectors e.g., iNOS and TNF-alpha, with restoration of the anti-inflammatory
interleukin IL-10. Additionally, it down-regulated the expression of caspase-3,
an apoptotic marker, thus favoring renal cell survival. Importantly, tangeretin
enhanced the cytotoxic actions of cisplatin in Hep3B and HCT-116 human cancer
cell lines. CONCLUSION: Together, these findings accentuate the dual benefit of
tangeretin: mitigation of renal injury-induced by cisplatin and enhancement of
its cytotoxic effects.
PMID- 27616469
TI - Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male
patients and its relation with glucose-insulin dynamic.
AB - Male hypogonadism is defined as the deficiency of testosterone or sperm
production synthesized by testicles or the deficiency of both. The reasons for
hypogonadism may be primary, meaning testicular or secondary, meaning
hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is
indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons.
Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing
follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted
is under the effect of many hormonal or stimulating factors. Kisspeptin is
present in many places of the body, mostly in hypothalamic anteroventral
periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect
on the metastasis of many tumors such as breast cancer and malign melanoma
metastases, and is called "metastin" for this reason. Kisspeptin is a strong
stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology,
there is gonadotropic hormone release indeficiency which cannot be clearly
described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over
30 years of age who have applied to Haydarpasa Education Hospital Endocrinology
and Metabolic Diseases Service were included in the study. Compared to the
control group, the effect of kisspeptin on male patients with hypogonatropic
hypogonadism and on insulin resistance developing in hypogonadism patients was
investigated in our study. A statistically significant difference was detected
between average kisspeptin measurements of the groups (p < 0.01). Kisspeptin
measurement of the cases in the patient group were detected significantly high.
No statistically significant relation was detected among kisspeptin and LH/FSH
levels. Although a positive low relation was detected between kisspeptin
measurements of patient group cases and homeostasis model assessment of insulin
resistance (HOMA-IR) measurements, this relation was statistically insignificant.
When the patient and control groups were compared for HOMA-IR, no statistically
significant difference was detected. The reason for high kisspeptin levels in the
patient group compared to the control group makes us consider that there may be a
GPR54 resistance or GnRH neuronal transfer pathway defect. When patients and
control groups were compared for HOMA-IR, the difference was not statistically
significant. It is considered that kisspeptin is one of the reasons for
hypogonatropic hypogonadism and has less effect on insulin resistance.
PMID- 27616470
TI - Mycobacterium tuberculosis exploits the formation of new blood vessels for its
dissemination.
AB - The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads
within the lung and leaves its primary niche to colonize other organs, thus
inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly
understood. Herein, we used a transcriptomic approach to investigate the host
cell gene expression profile in M. tuberculosis-infected human macrophages
(MUPhi). We identified 33 genes, encoding proteins involved in angiogenesis, for
which the expression was significantly modified during infection, and we show
that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected
MUPhi, in an RD1-dependent manner. In vivo these factors promote the formation of
blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF
inactivation, abolished mycobacterial spread from the infection site. In
accordance with our in vitro and in vivo results, we show that the level of VEGF
in TB patients is elevated and that endothelial progenitor cells are mobilized
from the bone marrow. These results strongly strengthen the most recent data
suggesting that mycobacteria take advantage of the formation of new blood vessels
to disseminate.
PMID- 27616471
TI - Long-term antibody persistence study (3 years after last dose) of the 7-valent
pneumococcal conjugate vaccine in young children in China.
AB - BACKGROUND: In a previous study, Chinese infants were vaccinated with 7-valent
pneumococcal conjugate vaccine (PCV7) ?7days before routine diphtheria, tetanus,
and acellular pertussis vaccine (DTaP); PCV7 administered concomitantly with DTaP
(PCV7+DTaP); or DTaP alone. This study examined antibody persistence at a single
time point 3years after the last vaccination. METHODS: Children who participated
in the prior PCV7 study were eligible to participate. A single blood sample was
drawn at enrollment. Immunoglobulin G (IgG) geometric mean concentrations (GMCs)
specific to the PCV7 serotypes and percentages of subjects with IgG ?0.35MUg/mL
were compared for subjects receiving PCV7 versus PCV7+DTaP (concomitant) and for
PCV7 or PCV7+DTaP (concomitant) versus DTaP alone. IgG concentrations at 3years
after the last vaccination were also compared with those after the infant series
and toddler dose. RESULTS: Three years after the last vaccination with PCV7 or
PCV7+DTaP (concomitant), IgG GMCs for most PCV7 serotypes were lower than after
the infant series or toddler dose but remained above prevaccination
concentrations. IgG GMC were similar between the PCV7 and PCV7+DTaP (concomitant)
groups for 5 out of 7 serotypes but serotypes 4 and 19F were significantly lower
in the PCV7+DTaP (concomitant) recipients. Three years after the last
vaccination, IgG GMCs were significantly higher for 6 of 7 PCV7 serotypes among
those receiving PCV7 or PCV7+DTaP (concomitant) compared with recipients of DTaP
alone. Among subjects receiving DTaP alone, serotype-specific antibody
concentrations were significantly higher for all serotypes 3years after the last
vaccination compared with after the infant series. CONCLUSION: Three years after
PCV7 vaccination, serotype-specific antibodies were lower than after the primary
infant series but higher than prevaccination levels and higher among subjects who
received PCV7 compared with those who did not. The immune response was comparable
in children who received PCV7 with and without concomitant DTaP. CLINICAL TRIAL
REGISTRATION: NCT01298544.
PMID- 27616472
TI - Squalene-containing licensed adjuvants enhance strain-specific antibody responses
against the influenza hemagglutinin and induce subtype-specific antibodies
against the neuraminidase.
AB - While seasonal influenza vaccines are usually non-adjuvanted, H1N1pdm09 vaccines
were formulated with different squalene-containing adjuvants, to enable the
reduction of antigen content thus increasing the number of doses available. To
comparatively assess the effects of these adjuvants on antibody responses against
matched and mismatched strains, and to correlate antibody levels with protection
from disease, ferrets were immunized with 2MUg of commercial H1N1pdm09 vaccine
antigen alone or formulated with different licensed adjuvants. The use of
squalene-containing adjuvants increased neutralizing antibody responses around
100-fold, and resulted in a significantly reduced viral load after challenge with
a matched strain. While all animals mounted strong total antibody responses
against the homologous H1N1 hemagglutinin (HA) protein, which correlated with the
respective neutralizing antibody titers, no reactivity with the divergent H3, H5,
H7, and H9 proteins were detected. Only the adjuvanted vaccines also induced
antibodies against the neuraminidase (NA) protein, which were able to also
recognize NA proteins from other N1 carrying strains. These findings not only
support the use of squalene-containing adjuvants in dose-sparing strategies but
also support speculations that the induction of NA-specific responses associated
with the use of these adjuvants may confer partial protection to heterologous
strains carrying the same NA subtype.
PMID- 27616473
TI - Interoceptive cues predicting exteroceptive events.
AB - The growing body of research on interoceptive conditioning has predominantly
focused on associative learning paradigms that investigated the formation of
intero-interoceptive or extero-interoceptive associations. Yet, little research
has explored whether interoceptive sensations can enter an intero-exteroceptive
association. Therefore, in an interoceptive conditioning paradigm, healthy
participants experienced a respiratory resistance for 8s, causing mild dyspnea
(interoceptive conditioned stimulus, CS), that was either paired to an aversive
electrocutaneous stimulus (unconditioned stimulus, US) (experimental condition,
n=25), or presented in an unpaired fashion (control condition, n=25) during the
acquisition phase. In a subsequent extinction phase, the US was not delivered
anymore. US-expectancy, skin conductance responses (SCR), and eyeblink startle
EMG were used as indices of associative learning. During acquisition, we observed
stronger US expectancies during the CS as compared to the intertrial interval in
the experimental group, but not in the control group, nor during extinction. In
line, only in the experimental group did skin conductance responses to the CS
increase across acquisition. The pattern of the eyeblink startle data did not
reach statistical significance. In sum, interoceptive sensations can become
associated with exteroceptive events.
PMID- 27616474
TI - Interactive effect of 5-HTTLPR genotype and age on sources of cortical rhythms in
healthy women.
AB - This study was aimed to localize the effects of 5-HTTLPR (serotonin-transporter
linked polymorphic region) on the age differences of spontaneous EEG activity in
women using neuroimaging analysis sLORETA (Standardized Low Resolution brain
Electromagnetic Tomography). DNA samples extracted from cheek swabs and resting
state EEG recorded at 60 standard leads were collected from young (YW, N=86, 18
35years) and older (OW, N=45; 55-80years) healthy women. We have shown that
advanced age was associated with increased posterior EEG desynchronization in
S'/S'. S' (LG allele was grouped with S alleles owing to its functional
equivalence and this group was labeled as S') genotype carriers denoted by
decrease of delta - beta1 current source density, and to a lesser extent in L/L
homozygotes denoted by decrease in delta activity. In heterozygotes OW, as
compared with heterozygotes YW, higher source density estimates of beta1 in
frontal and temporal cortex were observed. Age differences were more pronounced
in the right hemisphere in S'/S' and L/L carriers and in the left hemisphere in
heterozygotes. We also found that in OW, current source density estimates of
theta, alpha1, alpha2, alpha3 and beta1 sources in the right occipital lobe were
higher in S'/L than in S'/S' carriers. These results may have implications for
understanding 5-HTT-dependent variation in the effect of aging on brain activity.
PMID- 27616475
TI - Gene variants as risk factors for gastroschisis.
AB - In a population-based case-control study in California of 228 infants, we
investigated 75 genetic variants in 20 genes and risk of gastroschisis with
regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We
hypothesized that genes related to vascular compromise may interact with
environmental factors to affect the risk of gastroschisis. Haplotypes were
constructed for 75 gene variants using the HaploView program. Risk for
gastroschisis associated with each gene variant was calculated for both the
homozygotes and the heterozygotes, with the homozygous wildtypes as the referent.
Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by
logistic regression. We found 11 gene variants with increased risk and four
variants with decreased risk of gastroschisis for heterozygous (ORh ) or
homozygous variants (ORv ) genotypes. These included NOS3 (rs1036145) ORh = 0.4
(95% CI: 0.2-0.7); NOS3 (rs10277237) ORv = 2.7 (95% CI: 1.3-6.0); ADD1
(rs12503220) ORh = 2.9 (95% CI: 1.6-5.4), GNB3 (rs5443) ORh = 0.2 (95% CI: 0.1
0.5), ORv = 0.4 (95% CI: 0.2-0.9); ICAM1 (rs281428) ORv = 6.9 (95% CI: 2.1
22.9), ICAM1 (rs3093030) ORv = 2.6 (95% CI: 1.2-5.6); ICAM4 (rs281438) ORv =
4.9 (95% CI: 1.4-16.6), ICAM5 (rs281417) ORh = 2.1 (95% CI: 1.1-4.1), ORv = 4.8
(95% CI: 1.7-13.6); ICAM5 (rs281440) ORh = 23.7 (95% CI: 5.5-102.5), ORv = 20.6
(95% CI: 3.4-124.3); ICAM5 (rs2075741) ORv = 2.2 (95% CI: 1.1-4.4); NAT1 ORv =
0.3 (95% CI: 0.1-0.9). There were additional associations between several gene
variants and gastroschisis among women aged 20-24 and among mothers with and
without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further
investigation in additional populations and with the interaction of additional
environmental exposures. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616476
TI - Improving and accelerating the differentiation and functional maturation of human
stem cell-derived neurons: role of extracellular calcium and GABA.
AB - Neurons differentiated from pluripotent stem cells using established neural
culture conditions often exhibit functional deficits. Recently, we have developed
enhanced media which both synchronize the neurogenesis of pluripotent stem cell
derived neural progenitors and accelerate their functional maturation; together
these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and
generate authentic, mature synaptic networks of connected forebrain neurons from
a variety of induced pluripotent and embryonic stem cell lines. Such enhanced
rate and extent of synchronized maturation of pluripotent stem cell-derived
neural progenitor cells generates neurons which are characterized by a relatively
hyperpolarized resting membrane potential, higher spontaneous and induced action
potential activity, enhanced synaptic activity, more complete development of a
mature inhibitory GABAA receptor phenotype and faster production of electrical
network activity when compared to standard differentiation media. This entire
process - from pre-patterned neural progenitor to active neuron - takes 3 weeks
or less, making it an ideal platform for drug discovery and disease modelling in
the fields of human neurodegenerative and neuropsychiatric disorders, such as
Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia.
PMID- 27616477
TI - NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal
Neurometabolic Disorder of Early Childhood.
AB - To safeguard the cell from the accumulation of potentially harmful metabolic
intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed
NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX
and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding
the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX
repair system has been unknown. Exome sequencing revealed pathogenic biallelic
mutations in NAXE in children from four families with (sub-) acute-onset ataxia,
cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in
cerebrospinal fluid of all affected individuals. Disease onset was during the
second year of life and clinical signs as well as episodes of deterioration were
triggered by febrile infections. Disease course was rapidly progressive, leading
to coma, global brain atrophy, and finally to death in all affected individuals.
NAXE levels were undetectable in fibroblasts from affected individuals of two
families. In these fibroblasts we measured highly elevated concentrations of the
toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial
NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3)
supplementation might have therapeutic implications for this fatal disorder.
PMID- 27616478
TI - Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.
AB - Disruption of the establishment of left-right (L-R) asymmetry leads to situs
anomalies ranging from situs inversus totalis (SIT) to situs ambiguus
(heterotaxy). The genetic causes of laterality defects in humans are highly
heterogeneous. Via whole-exome sequencing (WES), we identified homozygous
mutations in PKD1L1 from three affected individuals in two unrelated families.
PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to
cause laterality defects in mouse and medaka fish models. Family 1 had one fetus
and one deceased child with heterotaxy and complex congenital heart
malformations. WES identified a homozygous splicing mutation,
c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron
42, in both affected individuals. In the second family, a homozygous c.5072G>C
(p.Cys1691Ser) missense mutation was detected in an individual with SIT and
congenital heart disease. The p.Cys1691Ser substitution affects a highly
conserved cysteine residue and is predicted by molecular modeling to disrupt a
disulfide bridge essential for the proper folding of the G protein-coupled
receptor proteolytic site (GPS) motif. Damaging effects associated with
substitutions of this conserved cysteine residue in the GPS motif have also been
reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C.
elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1.
The identification of bi-allelic PKD1L1 mutations recapitulates previous findings
regarding phenotypic consequences of loss of function of the orthologous genes in
mice and medaka fish and further expands our understanding of genetic
contributions to laterality defects in humans.
PMID- 27616480
TI - Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to
Intellectual Disability Accompanied by Epilepsy and Autistic Features.
AB - The risk of epilepsy among individuals with intellectual disability (ID) is
approximately ten times that of the general population. From a cohort of >5,000
families affected by neurodevelopmental disorders, we identified six
consanguineous families harboring homozygous inactivating variants in MBOAT7,
encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented
with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a
membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid
(AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol.
This study suggests a role for AA-containing phosphatidylinositols in the
development of ID accompanied by epilepsy and autistic features.
PMID- 27616481
TI - Mutations in GLDN, Encoding Gliomedin, a Critical Component of the Nodes of
Ranvier, Are Responsible for Lethal Arthrogryposis.
AB - Arthrogryposis multiplex congenita (AMC) is a developmental condition
characterized by multiple joint contractures resulting from reduced or absent
fetal movements. Through linkage analysis, homozygosity mapping, and exome
sequencing in four unrelated families affected by lethal AMC, we identified
biallelic mutations in GLDN in the affected individuals. GLDN encodes gliomedin,
a secreted cell adhesion molecule involved in the formation of the nodes of
Ranvier. Transmission electron microscopy of the sciatic nerve from one of the
affected individuals showed a marked lengthening defect of the nodes. The GLDN
mutations found in the affected individuals abolish the cell surface localization
of gliomedin and its interaction with its axonal partner, neurofascin-186
(NF186), in a cell-based assay. The axoglial contact between gliomedin and NF186
is essential for the initial clustering of Na+ channels at developing nodes.
These results indicate a major role of gliomedin in node formation and the
development of the peripheral nervous system in humans. These data indicate that
mutations of GLDN or CNTNAP1 (MIM: 616286), encoding essential components of the
nodes of Ranvier and paranodes, respectively, lead to inherited nodopathies, a
distinct disease entity among peripheral neuropathies.
PMID- 27616479
TI - De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an
Intellectual Disability Syndrome with Distinctive Dysmorphisms.
AB - Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin
remodeler involved in epigenetic regulation of gene transcription, DNA repair,
and cell cycle progression. Also known as Mi2beta, CHD4 is an integral subunit of
a well-characterized histone deacetylase complex. Here we report five individuals
with de novo missense substitutions in CHD4 identified through whole-exome
sequencing and web-based gene matching. These individuals have overlapping
phenotypes including developmental delay, intellectual disability, hearing loss,
macrocephaly, distinct facial dysmorphisms, palatal abnormalities,
ventriculomegaly, and hypogonadism as well as additional findings such as bone
fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu),
c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3),
affect evolutionarily highly conserved residues and are predicted to be
deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148
residues to be crucial for SNF2 function. Furthermore, mutations in the same
positions were reported in malignant tumors, and a de novo missense substitution
in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is
associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and
p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1
interaction. Based on these findings, the mutations potentially alter the complex
activity but not its formation. This report provides evidence for the role of
CHD4 in human development and expands an increasingly recognized group of
Mendelian disorders involving chromatin remodeling and modification.
PMID- 27616482
TI - GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes.
AB - Here we present a method of genome-wide inferred study (GWIS) that provides an
approximation of genome-wide association study (GWAS) summary statistics for a
variable that is a function of phenotypes for which GWAS summary statistics,
phenotypic means, and covariances are available. A GWIS can be performed
regardless of sample overlap between the GWAS of the phenotypes on which the
function depends. Because a GWIS provides association estimates and their
standard errors for each SNP, a GWIS can form the basis for polygenic risk
scoring, LD score regression, Mendelian randomization studies, biological
annotation, and other analyses. GWISs can also be used to boost power of a GWAS
meta-analysis where cohorts have not measured all constituent phenotypes in the
function. We demonstrate the accuracy of a BMI GWIS by performing power
simulations and type I error simulations under varying circumstances, and we
apply a GWIS by reconstructing a body mass index (BMI) GWAS based on a weight
GWAS and a height GWAS. Furthermore, we apply a GWIS to further our understanding
of the underlying genetic structure of bipolar disorder and schizophrenia and
their relation to educational attainment. Our analyses suggest that the
previously reported genetic correlation between schizophrenia and educational
attainment is probably induced by the observed genetic correlation between
schizophrenia and bipolar disorder and the previously reported genetic
correlation between bipolar disorder and educational attainment.
PMID- 27616485
TI - Global identification predicts gay-male identity integration and well-being among
Turkish gay men.
AB - In most parts of the world, hegemonic masculinity requires men to endorse
traditional masculine ideals, one of which is rejection of homosexuality.
Wherever hegemonic masculinity favours heterosexuality over homosexuality, gay
males may feel under pressure to negotiate their conflicting male gender and gay
sexual identities to maintain positive self-perceptions. However, globalization,
as a source of intercultural interaction, might provide a beneficial context for
people wishing to create alternative masculinities in the face of hegemonic
masculinity. Hence, we tested if global identification would predict higher
levels of gay-male identity integration, and indirectly subjective well-being,
via alternative masculinity representations for gay and male identities. A
community sample of 219 gay and bisexual men from Turkey completed the study.
Structural equation modelling revealed that global identification positively
predicted gay-male identity integration, and indirectly subjective well-being;
however, alternative masculinity representations did not mediate this
relationship. Our findings illustrate how identity categories in different
domains can intersect and affect each other in complex ways. Moreover, we discuss
mental health and well-being implications for gay men living in cultures where
they experience high levels of prejudice and stigma.
PMID- 27616486
TI - The value of disease prevention vs treatment.
AB - We present an integrated valuation model for diseases that are life-threatening.
The model extends the standard one-period value-per-statistical-life model to
three health prospects: healthy, ill, and dead. We derive willingness-to-pay
values for prevention efforts that reduce a disease's incidence rate as well as
for treatments that lower the corresponding health deterioration and mortality
rates. We find that the demand value of prevention always exceeds that of
treatment. People often overweight small risks and underweight large ones. We use
the rank dependent utility framework to explore how the demand for prevention and
treatment alters when people evaluate probabilities in a non-linear manner. For
incidence and mortality rates associated with common types of cancers, the
inverse-S shaped probability weighting found in experimental studies leads to a
significant increase in the demand values of both treatment and prevention.
PMID- 27616483
TI - GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic
Encephalopathy Treatable with NMDA Receptor Channel Blockers.
AB - N-methyl-D-aspartate receptors (NMDARs) are ligand-gated cation channels that
mediate excitatory synaptic transmission. Genetic mutations in multiple NMDAR
subunits cause various childhood epilepsy syndromes. Here, we report a de novo
recurrent heterozygous missense mutation-c.1999G>A (p.Val667Ile)-in a NMDAR gene
previously unrecognized to harbor disease-causing mutations, GRIN2D, identified
by exome and candidate panel sequencing in two unrelated children with epileptic
encephalopathy. The resulting GluN2D p.Val667Ile exchange occurs in the M3
transmembrane domain involved in channel gating. This gain-of-function mutation
increases glutamate and glycine potency by 2-fold, increases channel open
probability by 6-fold, and reduces receptor sensitivity to endogenous negative
modulators such as extracellular protons. Moreover, this mutation prolongs the
deactivation time course after glutamate removal, which controls the synaptic
time course. Transfection of cultured neurons with human GRIN2D cDNA harboring
c.1999G>A leads to dendritic swelling and neuronal cell death, suggestive of
excitotoxicity mediated by NMDAR over-activation. Because both individuals'
seizures had proven refractory to conventional antiepileptic medications, the
sensitivity of mutant NMDARs to FDA-approved NMDAR antagonists was evaluated.
Based on these results, oral memantine was administered to both children, with
resulting mild to moderate improvement in seizure burden and development. The
older proband subsequently developed refractory status epilepticus, with dramatic
electroclinical improvement upon treatment with ketamine and magnesium. Overall,
these results suggest that NMDAR antagonists can be useful as adjuvant epilepsy
therapy in individuals with GRIN2D gain-of-function mutations. This work further
demonstrates the value of functionally evaluating a mutation, enabling
mechanistic understanding and therapeutic modeling to realize precision medicine
for epilepsy.
PMID- 27616484
TI - Upfront targeted therapy for symptomatic melanoma brain metastases: paradigm
changing?
AB - The standard management of a single brain metastasis is usually maximal resection
when feasible followed by radiotherapy. In case of multiple lesions, several
options have to be considered depending on the natural behavior of the primary
tumor, the localization of brain lesions, their functional impact and related
symptoms. In case of life-threatening brain metastasis, debulking surgery is
often proposed first, with the risk of major bleeding and postponing the
initiation of other treatments. This approach is now challenged by the rapid
tumor shrinkage that could be observed with novel targeted therapies. Here we
report the case of a patient suffering from a melanoma with multiple brain
metastasis, treated with BRAF and MEK double blockade, with impressive and rapid
response.
PMID- 27616487
TI - Sporadic inclusion-body myositis: Recent advances and the state of the art in
2016.
AB - Sporadic inclusion-body myositis (sIBM) is the most frequent myopathy after 50
years of age. As the clinical presentation may often be typical, pathological
confirmation by muscle biopsy appears necessary, but sometimes difficult. Further
delineation of the framework of this particular disease, especially during its
early-onset stage, appears to be challenging. New classification of diagnostic
criteria as well as the identification of new diagnostic hallmarks appear to be
the two main tools towards to achieve this purpose. sIBM pathophysiology has long
been discussed and remains yet controversial. Since its initial description,
there have been two major pathogenic hypotheses: inflammatory and degenerative.
To date, the debate is still ongoing, as recent works support both
pathophysiological mechanisms, although the inflammatory process seems to be
slightly more preeminent in the recent literature. Treatment remains the most
disappointing aspect of the disease as, despite various therapeutic attempts, no
significant efficacy has been reported thus far. Nevertheless, advances in our
pathophysiological understanding of the disease are paving the way for further
therapeutic perspectives that might arise in the years to come. The objective of
the present work was to summarize the most significant data published on sIBM
during the past 2 years.
PMID- 27616488
TI - Antibiotic prophylaxis may not be necessary in patients with asymptomatic
bacteriuria undergoing intradetrusor onabotulinumtoxinA injections for neurogenic
detrusor overactivity.
AB - Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for
refractory neurogenic detrusor overactivity (NDO) present with chronic
bacteriuria. In these patients, antibiotic prophylaxis has been widely
recommended since bacteriuria might impair treatment efficacy and cause urinary
tract infections (UTI) but the evidence is limited. The aim of this study was to
evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic
bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between
06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of
273 treatment cycles were prospectively evaluated. Before treatment urine samples
were collected, patients with no clinical signs for UTI underwent
onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic
bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI
occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria,
respectively. Intradetrusor onabotulinumtoxinA injections were clinically and
urodynamically successful in 70% (192/273). There was no association between
bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23
1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95%
CI 0.43-1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be
critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA
injections, especially taking into account the alarming antibiotic resistance
worldwide.
PMID- 27616535
TI - Reduced Arch Length as a Factor for 4-Implant Immediate Function in the Maxilla:
A Technical Note and Report of 39 Patients Followed for 5 Years.
AB - PURPOSE: To determine whether maxillary arch length deficiency treated with a V-4
implant placement method is adequate for immediate functional loading during a 5
year follow-up. MATERIALS AND METHODS: Thirty-nine patients were treated with
maxillary immediate function from January 3, 2011 to February 28, 2011 and
followed for a period of 5 years. Arch length after implant placement was
measured retrospectively around the arch from the anterior sinus wall to the
contralateral anterior sinus wall in a mid-alveolar arc on the occlusal view of
the preoperative computed tomogram. Eight patients with an osseous arch length
shorter than 45 mm were treated with a V-4 pattern. Thirty-one patients with an
arch length longer than 45 mm were treated with an M-4 placement pattern. The aim
was to determine whether immediate function with a shorter arch length could be
obtained on the day of surgery using a V-4 placement and whether implant
stability would persist during the 5-year follow-up. Any surgical events,
including lost implants, were recorded in the charts. Late follow-up was
performed by panoramic films. RESULTS: During the 2-month treatment period, 39
patients (8 with V-4 placement and and 31 with M-4 placement) received maxillary
treatment. The 8 patients in the V-4 group had an arch length average of 36.0 mm
available for osseointegration. The 31 patients in the M-4 group had an arch
length average of 56.6 mm. There were 7 implant losses (and replacements) during
the 5-year follow-up, 1 in the V-4 group and 6 in the M-4 group. CONCLUSION: When
the arch length bone available for osseointegration is shorter than 45 mm, a V-4
placement strategy might enable successful 4-implant fixed denture support for
immediate function.
PMID- 27616536
TI - Tooth-Size Discrepancies in Patients Requiring Mandibular Advancement Surgery.
AB - PURPOSE: Numerous studies have shown that tooth size is an important key to ideal
occlusion. Bolton (Angle Orthod 28:13, 1958; 48:504, 1962) described a constant
ratio between the widths of the upper and lower teeth that must be present to
achieve an optimal occlusion. The purpose of this study was to determine the
incidence of Bolton discrepancies in patients with Class II malocclusion
scheduled for mandibular advancement surgery. PATIENTS AND METHODS: This study
included 126 patients (40 male, 86 female) with Class II malocclusion who had at
least a mandibular advancement as part of their surgical treatment. The
mesiodistal widths of the 6 anterior maxillary and mandibular teeth were measured
on preoperative models using a caliper. The measurements were used to compute the
anterior Bolton ratio. RESULTS: Seventy-three of 126 patients (57.9%) were found
to have an anterior Bolton ratio greater than the Bolton norm, indicating too
much lower tooth mass compared with the upper mass or too little upper tooth mass
compared with the lower mass. CONCLUSION: Tooth-size discrepancies are common in
patients requiring mandibular advancement surgery. This can make it difficult to
advance the mandible into a solid Class I relation at the time of surgery. Bolton
discrepancies should be considered when planning treatment with presurgical
orthodontics. In addition, if necessary, the width of the lower incisors should
be decreased or a space distal to the maxillary lateral incisors should be
created to allow the establishment of a solid Class I canine occlusion at the
time of surgery.
PMID- 27616537
TI - Can the value of the assistantship program be measured?
PMID- 27616539
TI - Pirfenidone treatment in idiopathic pulmonary fibrosis: nationwide Danish
results.
AB - BACKGROUND: Pirfenidone was approved by the European Medicines Agency and
introduced in most European countries in 2011 for treatment of idiopathic
pulmonary fibrosis (IPF). OBJECTIVE: To describe the national Danish experiences
of pirfenidone treatment for IPF during 30 months with respect to target
population, safety, adherence to the treatment and effect analysis in a well
characterised IPF population in a real-life setting. METHODS: Retrospective data
collection from medical records of all patients in Denmark with IPF from 2011 to
2014. Data included baseline demographics, high-resolution computed tomography
(HRCT), histopathology, forced vital capacity (FVC) and 6-min walk test (6MWT).
Longitudinal data on FVC, walk test, adherence to the treatment and vital status
were also collected. RESULTS: Pirfenidone treatment was initiated in 113
patients. Mean age was 69.6+/-8.1 years (+/-SD), and 71% were male. Definite IPF
diagnosis required thoracoscopic lung biopsy in 45 patients (39.8%). The
remaining 68 cases had a definite (64 patients) or possible usual interstitial
pneumonia (four patients) pattern on HRCT. Patients were followed for 0.1-33.8
months (median 9.4 months). Fifty-one patients (45.2%) needed dose adjustment, 18
(16%) patients discontinued therapy and 13 patients (11.5%) died. The annual mean
decline in FVC was 164 ml (SE 33.2). The decline in 6MWT was 18.2 m (SE 11.2).
Nausea (44.2%), fatigue (38.9%) and skin reactions (32.7%) were frequent adverse
events. CONCLUSION: Patients with IPF treated with pirfenidone experienced
tolerable adverse events. Patients were maintained on treatment due to a careful
follow-up and dose adjustment programme. The annual decline in physiological
parameters and mortality rate was comparable to previous randomised controlled
trials.
PMID- 27616538
TI - Effect of hepatic drug transporter polymorphisms on the pharmacokinetics of
mycophenolic acid in patients with severe renal dysfunction before renal
transplantation.
AB - 1. The objective of this study was to examine the association of UGT1A9, SLCO,
and ABCC polymorphisms with mycophenolic acid (MPA) pharmacokinetics in ABO blood
type (ABO) incompatible patients with severe renal dysfunction pre
transplantation. 2. In all patients, on day 14 after beginning mycophenolate
mofetil (MMF) treatment (1 week before transplantation) and on day 28 after renal
transplantation, samples were collected just prior to and 1, 2, 3, 4, 6, 9, and
12 h after oral MMF administration. 3. The median dose-adjusted AUC0-12 of MPA
after renal transplantation was significantly lower than before transplantation
(57.9 versus 76.5 MUg h/mL, respectively, p = 0.002). 4. Although the
enterohepatic circulation of MPA pre-transplantation was extremely high (57.6%),
this level was significantly reduced after renal transplantation (34.6%). 5. In
the multivariate analysis, pre-transplantation, patients with the SLCO1B3 334T
allele (p = 0.003), higher alanine aminotransferase (p = 0.002), and lower body
weight were independently predictive for a higher dose-adjusted AUC0-12 of MPA.
6. In patients with severe renal dysfunction pre-transplantation, MPA is excreted
mainly to bile from the liver, and as a consequence, the SLCO1B3 334T > G
polymorphism was found to be significantly associated with MPA exposure.
PMID- 27616540
TI - Changes in Root Canal Length Determined during Mechanical Preparation Stages and
Their Relationship with the Accuracy of Root ZX II.
AB - INTRODUCTION: The aim of this study was to determine the variations in root canal
length (RCL) occurring during endodontic treatment stages (initial, preflared,
and concluded) and correlate them with the accuracy of Root ZX II (RZX). METHODS:
After coronal access, 26 mandibular molars had the apical foramen of the 52
mesial canals standardized (250 MUm) and their respective initial RCL was
recorded (RCL1 = initial) by using a clinical microscope (*16) and manual K-file
instruments. By using the alginate model, sequential electronic measurements were
taken with the RZX. After the initial measurement (EM1), WaveOne Primary
instruments were used to prepare the cervical and middle thirds of the root
canals, and then the second RCL and EM measurements (RCL2/EM2 = preflared) were
obtained. Finally, mechanical preparation was concluded, and the measurement
procedures were repeated to obtain the final RCL and EM measurements (RCL3/EM3 =
concluded). RESULTS: Statistically significant differences were observed in all
comparisons in the RCL (P < .05). The RCL1 - RCL3 showed the highest variation
(0.6 mm), with the extent of specimens reduced by up to 1.75 mm. No statistically
significant differences were found in the accuracy of the RZX (P > .05); 100%
precision (+/- 0.5 mm) was found in all stages. CONCLUSIONS: Under the conditions
of this study, the authors concluded that during endodontic treatment, the extent
of the RCL was reduced, thereby jeopardizing control of the apical limit during
instrumentation and/or obturation. The RZX was extremely accurate in all
evaluated stages.
PMID- 27616541
TI - Influence of Smear Layer on the Antimicrobial Activity of a Sodium
Hypochlorite/Etidronic Acid Irrigating Solution in Infected Dentin.
AB - INTRODUCTION: The aim of this study was to evaluate the influence of the smear
layer on the antimicrobial activity of a 2.5% sodium hypochlorite (NaOCl)/9%
etidronic acid (HEBP) irrigating solution against bacteria growing inside dentin
tubules. METHODS: Dentin tubules were infected with Enterococcus faecalis by
centrifugation. After 5 days of incubation, the smear layer had formed in half of
the samples, which were then treated with 2.5% NaOCl either alone or combined
with 9% HEBP for 3 minutes. The percentage of dead cells in infected dentinal
tubules was measured using confocal laser scanning microscopy and the live/dead
technique. The smear layer on the surface of the root canal wall was also
observed by scanning electron microscopy. Results of the percentage of dead cells
were compared using parametric tests after subjecting data to the normalized
Anscombe transformation. The level of significance was P < .05. RESULTS: In the
absence of the smear layer, 2.5% NaOCl alone and combined with 9% HEBP showed
high antimicrobial activity without significant differences between the 2. The
smear layer reduced the antimicrobial activity of 2.5% NaOCl significantly,
whereas the solution with HEBP was not affected. No dentin tubules free of the
smear layer were obtained in the 2.5% NaOCl group. In the case of 2.5% NaOCl/9%
HEBP, 95.40% +/- 3.63% of dentin tubules were cleaned. CONCLUSIONS: The presence
of the smear layer reduced the antimicrobial activity of 2.5% NaOCl. The
combination of 2.5% NaOCl/9% HEBP exerted antimicrobial activity that was not
reduced by the smear layer.
PMID- 27616542
TI - Reliability and Repetition Effect of the Center of Pressure and Kinematics
Parameters That Characterize Trunk Postural Control During Unstable Sitting Test.
AB - BACKGROUND: Although unstable seat methodology has been used to assess trunk
postural control, the reliability of the variables that characterize it remains
unclear. OBJECTIVE: To analyze reliability and learning effect of center of
pressure (COP) and kinematic parameters that characterize trunk postural control
performance in unstable seating. The relationships between kinematic and COP
parameters also were explored. DESIGN: Test-retest reliability design. SETTINGS:
Biomechanics laboratory setting. PARTICIPANTS: Twenty-three healthy male
subjects. METHODS: Participants volunteered to perform 3 sessions at 1-week
intervals, each consisting of five 70-second balancing trials. A force platform
and a motion capture system were used to measure COP and pelvis, thorax, and
spine displacements. Reliability was assessed through standard error of
measurement (SEM) and intraclass correlation coefficients (ICC2,1) using 3
methods: (1) comparing the last trial score of each day; (2) comparing the best
trial score of each day; and (3) calculating the average of the three last trial
scores of each day. MAIN OUTCOME MEASUREMENTS: Standard deviation and mean
velocity were calculated to assess balance performance. RESULTS: Although
analyses of variance showed some differences in balance performance between days,
these differences were not significant between days 2 and 3. Best result and
average methods showed the greatest reliability. Mean velocity of the COP showed
high reliability (0.71 < ICC < 0.86; 10.3 < SEM < 13.0), whereas standard
deviation only showed a low to moderate reliability (0.37 < ICC < 0.61; 14.5 <
SEM < 23.0). Regarding the kinematic variables, only pelvis displacement mean
velocity achieved a high reliability using the average method (0.62 < ICC < 0.83;
18.8 < SEM < 23.1). Correlations between COP and kinematics were high only for
mean velocity (0.45 G substitution in the DMD gene, affecting the intron 10 acceptor splice site
and causing exon 11 skipping and an out-of-frame transcript. However, protein of
normal molecular weight but in reduced amounts was observed on Western Blot
analysis. Reverse transcription analysis on muscle RNA showed production, via
alternative splicing, of a transcript missing exon 11 as well as a low abundant
full-length transcript which is enough to avoid the severe Duchenne phenotype.
Our study showed that a reduced amount of full length dystrophin leads to a mild
form of Becker muscular dystrophy. These results confirm earlier findings that
low amounts of dystrophin can be associated with a milder phenotype, which is
promising for therapies aiming at dystrophin restoration.
PMID- 27616546
TI - Toxicological proteomic responses of halophyte Suaeda salsa to lead and zinc.
AB - The long term (30 days) toxicological effects of environmentally relevant
concentrations of Pb2+ (20MUg/L) and Zn2+ (100MUg/L) were characterized in Suaeda
salsa using proteomics techniques. The responsive proteins were related to
metabolism (Krebs cycle and Calvin cycle), protein biosynthesis, stress and
defense, energy, signaling pathway and photosynthesis in Pb2+, Zn2+ and Pb2++
Zn2+ exposed groups in S. salsa after exposures for 30 days. The proteomic
profiles also showed differential responses in S. salsa to metal exposures. In
Pb2+-treated group, the proteins were categorized into cystein metabolism and
pentose phosphate pathway. The responsive proteins were basically involved in
glutathione metabolism, glycolysis, cystein and methane metabolism, and voltage
dependent anion channel in Zn2+-treated group. In Pb2++ Zn2+-treated group, the
proecular mechanism at protein level remtein responses were devided into tyrosine
metabolism and glycolysis. Our results showed that the two typical heavy metals,
lead and zinc, could induce toxicological effects in halophyte S. salsa at
protein level.
PMID- 27616547
TI - Response to the editorial 'Menopausal health: the potential for fetal-placental
estrogen use'.
PMID- 27616548
TI - Can portion-controlled prepackaged foods promote weight loss?
PMID- 27616549
TI - Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and
endoplasmic reticulum stress: In vivo and in vitro evidence.
AB - Several pathogenetic factors have been involved in the onset and progression of
Parkinson's disease (PD), including inflammation, oxidative stress, unfolded
protein accumulation, and apoptosis. Palmitoylethanolamide (PEA), an endogenous N
acylethanolamine, has been shown to be a neuroprotective and anti-inflammatory
molecule, acting as a peroxisome proliferator activated receptor (PPAR)-alpha
agonist. In this study we investigated the effects of PEA on behavioral
alterations and the underlying pathogenic mechanisms in the 6-hydroxydopamine (6
OHDA)-induced model of PD in male mice. Additionally, we showed the involvement
of PPAR-alpha in PEA protective effect on SH-SY5Y neuroblastoma against 6-OHDA
damage. Here, we report that PEA (3-30mg/kg/days.c.) improved behavioral
impairments induced by unilateral intrastriatal injection of 6-OHDA. This effect
was accompanied by a significant increase in tyrosine hydroxylase expression at
striatal level, indicating PEA preserving effect on dopaminergic neurons.
Moreover, we found a reduction in the expression of pro-inflammatory enzymes,
i.e. inducible nitric oxide synthase and cyclooxygenase-2, a modulation between
pro- and anti-apoptotic markers, suggestive of PEA capability in controlling
neuroinflammation and cell death. Interestingly, PEA also showed protective
scavenging effect, through superoxide dismutase induction, and dampened unfolding
protein response, interfering on glucose-regulated protein 78 expression and PERK
eIF2alpha pathway. Similar data were found in in vitro studies, where PEA
treatment was found to rescue SH-SY5Y neuroblastoma cells from 6-OHDA-induced
damage and death, partly by inhibiting endoplasmic reticulum stress detrimental
response. Therefore, PEA, counteracting the pathogenetic aspects involved in the
development of PD, showed its therapeutic potential, possibly integrating current
treatments correcting dopaminergic deficits and motor dysfunction.
PMID- 27616550
TI - The novel H2S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective
effects against ischemia/reperfusion injury through activation of mitoKATP
channels and reduction of oxidative stress.
AB - The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator
of the cardiovascular system, particularly of myocardial function. Moreover, H2S
exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic
injury, and is considered an important mediator of "ischemic preconditioning",
through activation of mitochondrial potassium channels, reduction of oxidative
stress, activation of the endogenous "anti-oxidant machinery" and limitation of
inflammatory responses. Accordingly, H2S-donors, i.e. pro-drugs able to generate
exogenous H2S, are viewed as promising therapeutic agents for a number of
cardiovascular diseases. The novel H2S-donor 4-carboxy phenyl-isothiocyanate
(4CPI), whose vasorelaxing effects were recently reported, was tested here in
different experimental models of myocardial I/R. In Langendorff-perfused rat
hearts subjected to I/R, 4CPI significantly improved the post-ischemic recovery
of myocardial functional parameters and limited tissue injury. These effects were
antagonized by 5-hydroxydecanoic acid (a blocker of mitoKATP channels). Moreover,
4CPI inhibited the formation of reactive oxygen species. We found the whole
battery of H2S-producing enzymes to be present in myocardial tissue:
cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS) and 3
mercaptopyruvate sulfurtransferase (MPST). Notably, 4CPI down-regulated the post
ischemic expression of CSE. In Langendorff-perfused mouse hearts, 4CPI reduced
the post-ischemic release of norepinephrine and the incidence of ventricular
arrhythmias. In both rat and mouse hearts, 4CPI did not affect the degranulation
of resident mast cells. In isolated rat cardiac mitochondria, 4CPI partially
depolarized the mitochondrial membrane potential; this effect was antagonized by
ATP (i.e., the physiological inhibitor of KATP channels). Moreover, 4CPI
abrogated calcium uptake in the mitochondrial matrix. Finally, in an in vivo
model of acute myocardial infarction in rats, 4CPI significantly decreased I/R
induced tissue injury. In conclusion, H2S-donors, and in particular
isothiocyanate-based H2S-releasing drugs like 4CPI, can actually be considered a
suitable pharmacological option in anti-ischemic therapy.
PMID- 27616552
TI - Inside-out Ultraviolet-C Sterilization of Pseudomonas aeruginosa Biofilm In
Vitro.
AB - Biofilms are difficult to eradicate due to a protective architecture and create
major challenges in patient care by diminishing both host immune response and
therapeutic approaches. This study investigated a new strategy for treating
surface-attached biofilms by delivering germicidal UV through a material surface
in a process referred to as "inside-out sterilization" (IOS). Mature Pseudomonas
aeruginosa (ATCC(r) 27853TM ) biofilms were irradiated with up to 1400 mJ cm-2 of
germicidal UV from both ambient and IOS configurations. The lethal dose for the
ambient exposure group was 461 mJ cm-2 95% CI [292, 728] compared to the IOS
treatment group of 247 mJ cm-2 95% CI [187, 325], corresponding to 47% less UV
dosage for the IOS group (P < 0.05). This study demonstrated that with IOS, a
lower quantal dosage of UV energy is required to eradicate biofilm than with
ambient exposure by leveraging the organizational structure of the biofilm.
PMID- 27616551
TI - Modulation of monocytes by bioactive lipid anandamide in multiple sclerosis
involves distinct Toll-like receptors.
AB - Monocytes are believed to be involved in the immunopathogenesis of multiple
sclerosis (MS). The aim of this study was to investigate their role in MS and
their immunomodulation by the endocannabinoid system (ECS), a novel target for
the treatment of this disease. We compared the level of cytokine production from
monocytes in healthy subjects and MS patients upon stimulation with viral or
bacterial Toll-like receptors (TLR) and we evaluated the ECS immunomodulatory
role in these cells. Here we show that MS monocytes produced more TNF-alpha, IL
12 and IL-6 following activation of TLR2/4 with LPS or of TLR5 with flagellin, as
opposed to TLR7/8 stimulation with R848. Furthermore AEA, the main
endocannabinoid, suppressed cytokine production and release from healthy
monocytes upon stimulation with both bacterial and viral TLR receptors but not in
cells from MS patients, where its immunosuppressive activity was TLR7/8
dependent. Altered expression levels of key ECS members in MS monocytes
paralleled these data. Our data disclose a distinct immunomodulatory effect of
AEA and an alteration of AEA-related members of the ECS in monocytes from MS
patients that involves viral but not bacterial TLR. These findings not only may
help to better understand the role of monocytes in MS immunopathogenesis but also
could be of help to exploit new endocannabinoid-based drugs that target innate
immune cells.
PMID- 27616553
TI - Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory
mantle cell lymphoma.
AB - In this multicenter, single-arm, phase II study, the efficacy and safety of
ibrutinib were examined in Japanese patients with relapsed or refractory mantle
cell lymphoma (MCL). Patients (age >=20 years) with relapsed or refractory MCL
who had progressed after receiving at least one prior treatment regimen, were
enrolled. Patients were treated with oral ibrutinib (560 mg once daily; 28-day
cycle) until disease progression (or relapse), unacceptable toxicity, or study
end. The primary end-point was overall response rate. Secondary end-points
included duration of response (DOR), time to response, progression-free survival
(PFS), overall survival, and safety. Of the 16 patients who received treatment, 5
patients discontinued the study (progressive disease, 4; sepsis, 1). Median
duration of ibrutinib exposure was 6.5 months (range, 2.8-8.3 months). The
overall response rate was 87.5% (90% confidence interval, 65.6-97.7; complete
response = 2 [12.5%]; partial response = 12 [75.0%]). Median time to response for
all responders (n = 14) was 1.8 months (range, 0.7-5.3 months). The median DOR
and PFS were not estimable due to censoring (range: DOR, 1.1-6.4+ months; PFS,
2.8-8.0+ months). Overall survival data were immature due to the limited
observation period. A total of 8/16 patients (50%) had at least one grade 3
adverse event (AE), and 5 (31.3%) patients reported serious AEs. The most
commonly reported AEs were diarrhea and stomatitis (37.5% each), platelet count
decrease (31.3%), and anemia (25%). Overall, orally administered single agent
ibrutinib was efficacious with an acceptable safety profile in Japanese patients
with relapsed or refractory MCL. Clinical trial registration NCT02169180
(ClinicalTrials.gov).
PMID- 27616554
TI - Occurrence and molecular characterization of Sapelovirus A in diarrhea and non
diarrhea feces of different age group pigs in one Korean pig farm.
AB - To determine the occurrence and genetic diversity of Sapelovirus A (SV-A) in
diarrhea and non-diarrhea feces of Korean pigs, 110 specimens from different age
groups of pigs in the same farm were analyzed by RT-nested PCR. SV-As were
detected in 60% of both diarrhea and non-diarrhea specimens regardless of age
groups with primer pairs for 2C region, in which all diarrhea samples were co
infected by other enteric pathogens. Phylogenetical analysis of partial VP1
region showed that our strains and several other Korean strains belonged to
cluster I, distinct from some strains reported in Korea and other countries.
These data indicate that genetically distinct SV-As are frequently detected in
Korean pigs irrespective of diarrhea and age.
PMID- 27616555
TI - A case of acute postoperative transitory sialadenosis of the submandibular glands
in a healthy dog.
AB - A 1-year-old healthy female cross-breed dog, weighing 4.5 kg, was scheduled for
elective neutering. Fentanyl (5 ug/kg) and propofol (4 mg/kg) were administered
intravenously (IV) to induce anesthesia, which was maintained with isoflurane and
a constant fentanyl infusion rate (10 ug/kg/hr). During the recovery from the
anesthesia, the presence of bilateral dense submandibular masses was recognized,
as was the excessive secretion of saliva. An ultrasound examination was performed
and revealed bilateral abnormally-diffused enlargement of the submandibular
salivary glands. A cytology examination was conducted, and no signs of
abnormality were found. The size of the swellings subsequently diminished,
completely subsiding after 2 hr, as did the hyper-salivation. To the authors'
knowledge, this represents the first case report of an acute transient swelling
of submandibular glands after general anesthesia in a dog.
PMID- 27616556
TI - Identification of the first case of atypical scrapie in Japan.
AB - A Corriedale ewe was confirmed as the first atypical scrapie case during an
active surveillance program for transmissible spongiform encephalopathies in
small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of
PRNP. The animal showed clinical neurological signs possibly due to listeriosis
before culling. Western blot analysis showed an unusual multiple banded pattern
with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative
meningoencephalitis caused by listeriosis in the brainstem. Fine granular to
globular immunostaining of disease-associated prion proteins was mainly detected
in the neuropil of the spinal tract of the trigeminal nerve and in the white
matter of the spinocerebellar tract. Based on these results, this case was
conclusively diagnosed as atypical scrapie with encephalitic listeriosis.
PMID- 27616557
TI - Neurological Disease as a Failure of Brain-Immune Crosstalk: The Multiple Faces
of Neuroinflammation.
AB - Neuroinflammation is common to various diseases of the central nervous system
(CNS), but its imprecise definition has led to many misconceptions in research
and clinical approaches. It is now recognized that neuroinflammation in chronic
neurodegenerative conditions, including Alzheimer's disease (AD) and age-related
dementia, is distinct from the inflammation that accompanies relapsing-remitting
multiple sclerosis (RRMS), and its experimental animal model, experimental
autoimmune encephalomyelitis (EAE). Here, we discuss the discrete features of
inflammation in different CNS pathologies, given the current understanding of the
CNS-immune crosstalk; the roles of the immune cells that are involved, their
phenotypes, and their location and route of entry to the CNS. Understanding the
term neuroinflammation to encompass a broad range of disease-specific conditions
is essential for finding effective therapeutic approaches for these pathologies.
PMID- 27616558
TI - The Role of the Microbiota in Shaping Infectious Immunity.
AB - Humans are meta-organisms that maintain a diverse population of microorganisms on
their barrier surfaces, collectively named the microbiota. Since most pathogens
either cross or inhabit barrier surfaces, the microbiota plays a critical and
often protective role during infections, both by modulating immune system
responses and by mediating colonization resistance. However, the microbiota can
also act as a reservoir for opportunistic microorganisms that can 'bloom',
significantly complicating diseases of barrier surfaces by contributing to
inflammatory immune responses. This review discusses our current understanding of
the complex interactions between the host, its microbiota, and pathogenic
organisms, focusing in particular on the intestinal mucosa.
PMID- 27616560
TI - Variation in common preschool sleep problems as an early predictor for depression
and anxiety symptom severity across time.
AB - BACKGROUND: Child and adolescent psychopathology has been linked to increased
sleep problems, but there has been less investigation of this relationship in
younger samples with early-onset psychopathology. This study examined three
specific but commonly observed aspects of sleep behaviors in young children - (i)
Sleep onset latency, (ii) Refusal to sleep alone, and (iii) Nighttime awakenings
measured during preschool, and investigated whether these sleep problems
predicted anxiety and/or depression across the next 6 years until school age
(ages 9-13). METHODS: Data were analyzed from N = 292 participants from a
prospective longitudinal study of preschool-age children (ages 3-6). At baseline,
parent-reported clinical interviews of psychiatric symptoms, as well as sleep
problems were conducted using the Preschool-Age Psychiatric Assessment (PAPA).
Follow-up clinical interviews were also conducted annually through school age
using the Childhood and Adolescent Psychiatric Assessment (CAPA). RESULTS: Parent
reported sleep onset latency and refusal to sleep alone were significant
independent predictors of MDD and anxiety severity, but not ADHD severity across
time, even after controlling for family income-to-needs ratio and maternal
internalizing psychopathology. In exploratory analyses using only healthy
preschoolers, parent-reported sleep onset latency and refusal to sleep alone also
predicted anxiety severity. CONCLUSIONS: We demonstrate that specific, yet
relatively common sleep problems predict diagnostic severity of depression and
anxiety across time, but not ADHD. Increased clinical attention to and screening
for sleep onset latency and refusal to sleep alone during preschool may be
warranted.
PMID- 27616561
TI - Present and future of biologic drugs in primary Sjogren's syndrome.
AB - INTRODUCTION: Primary Sjogren's (pSS) syndrome is a chronic, autoimmune, and
systemic disease characterized by xerostomia, xerophthalmia, muscle pain and
fatigue. The disease may be complicated by a systemic involvement, such as a
pulmonary fibrosis or the development of lymphoma which severely worsens the
prognosis. Actually, there are no recommendations for the management of pSS.
However, recent advances in the understanding of its pathogenesis have uncovered
some pathways that have potential as therapeutic targets. Areas covered: In this
review, the authors present the biologic drugs potentially valuable to the
treatment of pSS in light of its physiopathology with a 'bird's eye' view of
future prospects. The authors took into account relevant studies published from
2004 to 2016. Expert opinion: Biological treatment in pSS is a promising
opportunity to potentially control disease activity and prevent its complication.
Currently, inhibition of B-cell and IL-17 pathways seem to be the most promising
avenues. New achievements in the knowledge of pSS pathophysiology are necessary
in order to try to simultaneously predict the predominant pathogenic pathway, the
kind of patients at major risk to develop a more severe disease, and the
appropriate biological therapy to use.
PMID- 27616562
TI - The effect of manual therapy on pulmonary function in healthy adults.
AB - Manual therapy is suggested as a potentially therapeutic intervention that may
improve pulmonary function. However, this form of therapy is largely based on
clinical observations and hypothetical models rather than mechanistic knowledge.
This study examined the influence of a single session of manual therapy applied
to the thoracic spine and thorax on dynamic pulmonary function over an extended
time frame in healthy adults. 21 healthy individuals (14 males) aged 19-35 (mean
[SD] age = 23 [3.9], BMI [SD] = 22.97 [2.41]) completed one experimental testing
session consisting of five pulmonary function tests and the delivery of a manual
therapy intervention. Pulmonary function was measured at baseline and 1 minute,
10 minutes, 20 minutes and 30 minutes following the intervention. Baseline mean
(SD) forced vital capacity (FVC), forced expired volume in 1 second (FEV1) and
maximal voluntary ventilation (MVV) were 5.55(1.23 L), 4.64(0.92 L) and
165.7(40.0L min(-1)) respectively. The mean (SD) FEV1/FVC ratio was 0.84(0.07).
There were no statistically significant changes in any of the pulmonary function
measures following the manual therapy intervention. Our findings do not support
the use of manual therapy to provide a short-term benefit in respiratory function
to healthy adults.
PMID- 27616563
TI - Evaluation of professional supervision in Aotearoa/New Zealand: An
interprofessional study.
AB - The evaluation of professional supervision has been a focus for discussion in the
supervision literature over past decades. A review of the literature in this
area, however, suggests that evaluation has been differently defined, variously
addressed, and a range of outcomes reported. The present study reports the
findings of the first stage of a three-stage study of evaluation in professional
supervision in Aotearoa/New Zealand. Experienced practitioners from the four
professions of counselling, mental health nursing, psychology, and social work
were interviewed to explore how evaluation in professional supervision is
understood and actioned in practice. Twenty four semistructured interviews were
conducted with supervisees, supervisors, and managers from each of the identified
professions. The findings from these interviews indicate that a majority of
participants applied some form of evaluation to their supervision arrangement.
These evaluations, however, did not reflect an overarching organizational or
professional culture of formal evaluation, but rather, an individualized ad-hoc
process initiated by one or both of the participants (supervisor and supervisee).
These evaluations focussed predominantly on the process, rather than the
outcomes, of supervision. While many respondents expressed interest in a formal
process for evaluating supervision, a number of concerns were also raised. These
concerns included a lack of evaluation skills and resource, the potential for
formal evaluation to have a negative impact on the supervision relationship, the
importance of maintaining the boundaries of confidentiality, and a wariness
regarding the possible use of any information gathered.
PMID- 27616564
TI - Non-Debye frustrated hydration steers biomolecular association: interfacial
tension for the drug designer.
AB - Many cellular functions involve the assembly of biomolecular complexes, a process
mediated by water that gets displaced as subunits bind. This process affects
water frustration, that is, the number of unmet hydrogen-bonding opportunities at
the protein-water interface. By searching for least-frustrated aqueous
interfaces, this study delineates the role of frustration in steering molecular
assemblage. The search entails a trajectory sampling using a functional that
measures the gradient of frustration and computing the resulting non-Debye
electrostatics within relaxation times for coupled protein-water systems. The
minimal frustration principle is validated against spectroscopic measurements of
frustration-dependent dielectric relaxation, affinity scanning of protein-protein
interfaces, and NMR-inferred association propensities of protein-complex
intermediates. The methods are applied to drug design, revealing the targetable
nature of the aqueous interface.
PMID- 27616565
TI - Orthostatic hypotension does not predict recurrent falling in a nursing home
population.
AB - OBJECTIVE: Most studies regard orthostatic hypotension (OH) as a causal factor
for falls. However, the evidence is lacking for this assumption. We aimed to
investigate the relationship between orthostatic hypotension and fall incidents
in nursing home residents. METHODS: A total of 249 patients was included in a
prospective observational cohort study of nursing home residents. Falls were
prospectively registered. Cox proportional hazard modelling and the conditional
frailty model were used to analyse the relationship between OH and (recurrent)
falling. RESULTS: Among the 249 patients, 450 falls were recorded during follow
up and OH was present in 93 out of 249 patients. No significant associations were
found between OH and the first fall incident (Hazard Ratio (HR) 1.01 (95%
Confidence Interval (CI) 0.60-1.69) and recurrent falling (HR 1.21 (95%CI 0.65
2.24)). CONCLUSIONS: Although falling and OH were both highly prevalent in
nursing home residents, no relationship between OH and falling was found.
PMID- 27616559
TI - Testosterone and reproductive effort in male primates.
AB - Considerable evidence suggests that the steroid hormone testosterone mediates
major life-history trade-offs in vertebrates, promoting mating effort at the
expense of parenting effort or survival. Observations from a range of wild
primates support the "Challenge Hypothesis," which posits that variation in male
testosterone is more closely associated with aggressive mating competition than
with reproductive physiology. In both seasonally and non-seasonally breeding
species, males increase testosterone production primarily when competing for
fecund females. In species where males compete to maintain long-term access to
females, testosterone increases when males are threatened with losing access to
females, rather than during mating periods. And when male status is linked to
mating success, and dependent on aggression, high-ranking males normally maintain
higher testosterone levels than subordinates, particularly when dominance
hierarchies are unstable. Trade-offs between parenting effort and mating effort
appear to be weak in most primates, because direct investment in the form of
infant transport and provisioning is rare. Instead, infant protection is the
primary form of paternal investment in the order. Testosterone does not inhibit
this form of investment, which relies on male aggression. Testosterone has a wide
range of effects in primates that plausibly function to support male competitive
behavior. These include psychological effects related to dominance striving,
analgesic effects, and effects on the development and maintenance of the
armaments and adornments that males employ in mating competition.
PMID- 27616567
TI - Targeted sequencing of genome wide significant loci associated with bone mineral
density (BMD) reveals significant novel and rare variants: the Cohorts for Heart
and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study.
AB - Background: Bone mineral density (BMD) is a heritable phenotype that predicts
fracture risk. We performed fine-mapping by targeted sequencing at WLS, MEF2C,
ARHGAP1/F2 and JAG1 loci prioritized by eQTL and bioinformatic approaches among
56 BMD loci from our previous GWAS meta-analysis. Targeted sequencing was
conducted in 1,291 Caucasians from the Framingham Heart Study ( n = 925) and
Cardiovascular Health Study ( n = 366), including 206 women and men with extreme
low femoral neck (FN) BMD. A total of 4,964 sequence variants (SNVs) were
observed and 80% were rare with MAF <1%. The associations between previously
identified SNPs in these loci and BMD, while nominally significant in sequenced
participants, were no longer significant after multiple testing corrections.
Conditional analyses did not find protein-coding variants that may be responsible
for GWAS signals. On the other hand, in the sequenced subjects, we identified
novel associations in WLS , ARHGAP1 , and 5' of MEF2C ( P- values < 8x10 - 5 ;
false discovery rate (FDR) q-values < 0.01) that were much more strongly
associated with BMD compared to the GWAS SNPs. These associated SNVs are less
common; independent from previous GWAS signals in the same loci; and located in
gene regulatory elements. Our findings suggest that protein-coding variants in
selected GWAS loci did not contribute to GWAS signals. By performing targeted
sequencing in GWAS loci, we identified less-common and rare non-coding SNVs
associated with BMD independently from GWAS common SNPs, suggesting both common
and less-common variants may associate with disease risks and phenotypes in the
same loci.
PMID- 27616570
TI - Crystal Structures of Peptide Deformylase from Rice Pathogen Xanthomonas oryzae
pv. oryzae in Complex with Substrate Peptides, Actinonin, and Fragment Chemical
Compounds.
AB - Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight on rice; this species
is one of the most destructive pathogenic bacteria in rice cultivation worldwide.
Peptide deformylase (PDF) catalyzes the removal of the N-formyl group from the N
terminus of newly synthesized polypeptides in bacterial cells and is an important
target to develop antibacterial agents. We determined crystal structures of Xoo
PDF (XoPDF) at up to 1.9 A resolution, which include apo, two substrate-bound
(methionine-alanine or methionine-alanine-serine), an inhibitor-bound
(actinonin), and six fragment chemical-bound structures. Six fragment chemical
compounds were bound in the substrate-binding pocket. The fragment chemical-bound
structures were compared to the natural PDF inhibitor actinonin-bound structure.
The fragment chemical molecules will be useful to design an inhibitor specific to
XoPDF and a potential pesticide against Xoo.
PMID- 27616571
TI - H-theorem in quantum physics.
AB - Remarkable progress of quantum information theory (QIT) allowed to formulate
mathematical theorems for conditions that data-transmitting or data-processing
occurs with a non-negative entropy gain. However, relation of these results
formulated in terms of entropy gain in quantum channels to temporal evolution of
real physical systems is not thoroughly understood. Here we build on the
mathematical formalism provided by QIT to formulate the quantum H-theorem in
terms of physical observables. We discuss the manifestation of the second law of
thermodynamics in quantum physics and uncover special situations where the second
law can be violated. We further demonstrate that the typical evolution of energy
isolated quantum systems occurs with non-diminishing entropy.
PMID- 27616572
TI - Regioisomer-Specific Mechanochromism of Naphthopyran in Polymeric Materials.
AB - Transformation of naphthopyran into a colored merocyanine species in polymeric
materials is achieved using mechanical force. We demonstrate that the
mechanochemical reactivity of naphthopyran is critically dependent on the
regiochemistry, with only one particular substitution pattern leading to
successful mechanochemical activation. Two alternative regioisomers with
different polymer attachment points are demonstrated to be mechanochemically
inactive. This trend in reactivity is accurately predicted by DFT calculations,
reinforcing predictive capabilities in mechanochemical systems. We rationalize
the reactivity differences between naphthopyran regioisomers in terms of the
alignment of the target C-O pyran bond with the direction of the applied
mechanical force and its effect on mechanochemical transduction along the
reaction coordinate.
PMID- 27616569
TI - Transition states and cell fate decisions in epigenetic landscapes.
AB - Waddington's epigenetic landscape is an abstract metaphor frequently used to
represent the relationship between gene activity and cell fates during
development. Over the past few years, it has become a useful framework for
interpreting results from single-cell transcriptomics experiments. It has led to
the proposal that, during fate transitions, cells experience smooth, continuous
progressions of global transcriptional activity, which can be captured by
(pseudo)temporal dynamics. Here, focusing strictly on the fate decision events,
we suggest an alternative view: that fate transitions occur in a discontinuous,
stochastic manner whereby signals modulate the probability of the transition
events.
PMID- 27616573
TI - Unique coenzyme binding mode of hyperthermophilic archaeal sn-glycerol-1
phosphate dehydrogenase from Pyrobaculum calidifontis.
AB - A gene encoding an sn-glycerol-1-phosphate dehydrogenase (G1PDH) was identified
in the hyperthermophilic archaeon Pyrobaculum calidifontis. The gene was
overexpressed in Escherichia coli, and its product was purified and
characterized. In contrast to conventional G1PDHs, the expressed enzyme showed
strong preference for NADH: the reaction rate (Vmax ) with NADPH was only 2.4% of
that with NADH. The crystal structure of the enzyme was determined at a
resolution of 2.45 A. The asymmetric unit consisted of one homohexamer.
Refinement of the structure and HPLC analysis showed the presence of the bound
cofactor NADPH in subunits D, E, and F, even though it was not added in the
crystallization procedure. The phosphate group at C2' of the adenine ribose of
NADPH is tightly held through the five biased hydrogen bonds with Ser40 and
Thr42. In comparison with the known G1PDH structure, the NADPH molecule was
observed to be pushed away from the normal coenzyme binding site. Interestingly,
the S40A/T42A double mutant enzyme acquired much higher reactivity than the wild
type enzyme with NADPH, which suggests that the biased interactions around the
C2'-phosphate group make NADPH binding insufficient for catalysis. Our results
provide a unique structural basis for coenzyme preference in NAD(P)-dependent
dehydrogenases. Proteins 2016; 84:1786-1796. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616574
TI - Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non
small cell lung cancer cells.
AB - AIM: Inhibition of heat shock protein (Hsp90) has been proven to be effective in
overriding primary and acquired resistance of kinase inhibitors. In this study,
we investigated the role of FS-108, a newly developed Hsp90 inhibitor, to
overcome gefitinib resistance in EGFR mutant non-small cell lung cancer cells.
METHODS: Cell proliferation was assessed using the SRB assay. Cell cycle
distribution and apoptosis were analyzed by flow cytometry. Protein expression
was examined by Western blotting. The in vivo effectiveness of FS-108 was
determined in an NCI-H1975 subcutaneous xenograft model. RESULTS: FS-108
triggered obvious growth inhibition in gefitinib-resistant HCC827/GR6, NCI-H1650
and NCI-H1975 cells through inducing G2/M phase arrest and apoptosis. FS-108
treatment resulted in a remarkable degradation of key client proteins involved in
gefitinib resistance and further abrogated their downstream signaling pathways.
Interestingly, FS-108 alone exerted an identical or superior effect on
circumventing gefitinib resistance compared to combined kinase inhibition.
Finally, the ability of FS-108 to overcome gefitinib resistance in vivo was
validated in an NCI-H1975 xenograft model. CONCLUSION: FS-108 is a powerful agent
that impacts the survival of gefitinib-resistant cells in vitro and in vivo
through targeting Hsp90.
PMID- 27616575
TI - Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated
rat thoracic aorta.
AB - AIM: Ginsenosides are considered to be the major pharmacologically active ginseng
constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite
of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on
isolated rat thoracic aortas as well as its vasorelaxant mechanisms. METHODS:
Aortic rings with or without endothelium were prepared from Wistar rats and
suspended in organ-chambers. The changes in tension of the preparations were
recorded through isometric transducers connected to a data acquisition system.
The aortic rings were precontracted with phenylephrine (PE, 1 MUmol/L) or high-K+
(80 mmol/L). RESULTS: Application of 20(S)-PPD (21.5-108.5 MUmol/L) caused
concentration-dependent vasodilation of endothelium-intact aortic rings
precontracted with PE or high-K+, which resulted in the EC50 values of 90.4 or
46.5 MUmol/L, respectively. The removal of endothelium had no effect on 20(S)-PPD
induced relaxation. The vasorelaxant effect of 20(S)-PPD was also not influenced
by the preincubation with beta-adrenergic receptor antagonist propranolol, or
with ATP-sensitive K+ channel blocker glibenclamide, voltage-dependent K+ channel
blocker 4-AP and inward rectifier K+ channel blocker BaCl2, whereas it was
significantly attenuated by the preincubation with Ca2+-activated K+ (BKCa)
channel blocker TEA (1 mmol/L). Furthermore, the inhibition of NO synthesis, cGMP
and prostacyclin pathways did not affect the vasorelaxant effect of 20(S)-PPD. In
Ca2+-free solution, 20(S)-PPD (108.5 MUmol/L) markedly decreased the
extracellular Ca2+-induced contraction in aortic rings precontracted with PE or
high-K+ and reduced PE-induced transient contraction. Voltage-dependent Ca2+
channel antagonist nifedipine inhibited PE-induced contraction; further
inhibition was observed after the application of receptor-operated Ca2+ channel
inhibitor SK&F 96365 or 20(S)-PPD. CONCLUSION: 20(S)-PPD induces vasorelaxation
via an endothelium-independent pathway. The inhibition of voltage-dependent Ca2+
channels and receptor-operated Ca2+ channels and the activation of Ca2+-activated
K+ channels are probably involved in the relaxation.
PMID- 27616576
TI - Bibenzyl compound 20c protects against endoplasmic reticulum stress in
tunicamycin-treated PC12 cells in vitro.
AB - AIM: Accumulation of alpha-synuclein (alpha-syn) in the brain is a characteristic
of Parkinson's disease (PD). In this study, we investigated whether treatment
with tunicamycin, an endoplasmic reticulum (ER) stress inducer, led to the
accumulation of alpha-syn in PC12 cells, and where alpha-syn protein was
accumulated, and finally, whether bibenzyl compound 20c, a novel compound
isolated from Gastrodia elata (Tian ma), could alleviate the accumulation of
alpha-syn and ER stress activation in tunicamycin-treated PC12 cells. METHODS:
PC12 cells were treated with tunicamycin for different time (6 h, 12 h, 24 h, 48
h). Cell viability was determined by a MTT assay. Subcellular fractions of ER and
mitochondria were extracted with the Tissue Endoplasmic reticulum Isolation Kit.
The levels of alpha-syn protein and ER-stress-associated downstream chaperones
were detected using Western blots and immunofluorescence. RESULTS: Treatment of
PC12 cells with tunicamycin (0.5-10 MUg/mL) dose-dependently increased the
accumulation of alpha-syn monomer (19 kDa) and oligomer (55 kDa), and decreased
the cell viability. Accumulation of the two forms of alpha-syn was observed in
both the ER and mitochondria with increasing treatment time. Co-treatment with
20c (10-5 mol/L) significantly increased the viability of tunicamycin-treated
cells, reduced the level of alpha-syn protein and suppressed ER stress activation
in the cells, evidenced by the reductions in phosphorylation of eIF2alpha and
expression of spliced ATF6 and XBP1. CONCLUSION: Tunicamycin treatment caused
accumulation of alpha-syn monomer and oligomer in PC12 cells. Bibenzyl compound
20c reduces the accumulation of alpha-syn and inhibits the activation of ER
stress, which protected PC12 cells against the toxicity induced by tunicamycin.
PMID- 27616577
TI - Layer II of placental syncytiotrophoblasts expresses MDR1 and BCRP at the apical
membrane in rodents.
AB - The purpose of this study is to clarify the subcellular localizations of
multidrug resistance protein 1 (MDR1)/ABCB1 and breast cancer resistance protein
(BCRP)/ABCG2 in the rodent placental SynT bilayer, i.e., a maternal-facing (SynT
I) layer and a fetal-facing (SynT-II) layer. In double immunofluorescence
staining, the signals of MDR1 and BCRP appeared midway between the signals of
glucose transporter 1 on the apical membrane of SynT-I and the basal plasma
membrane of SynT-II, and mostly overlapped with signals of connexin 26, which
forms gap junctions between SynT-I and SynT-II. In detail, median intensities
(pixels) of the MDR1 and BCRP signals were significantly closer to the fetal
circulation as compared to the location of connexin 26 signals. In double in situ
hybridization studies, the signals of Mdr1b mRNA mostly overlapped with those of
Syncytin-B, a SynT-II marker. In conclusion, MDR1 and BCRP are expressed on
apical membranes of the rodent placental SynT-II layer.
PMID- 27616578
TI - Early career mentoring through the American Society of Pediatric
Hematology/Oncology: Lessons learned from a pilot program.
AB - BACKGROUND: Effective networking and mentorship are critical determinants of
career satisfaction and success in academic medicine. The American Society of
Pediatric Hematology/Oncology (ASPHO) mentoring program was developed to support
Early Career (EC) members. Herein, the authors report on the initial 2-year
outcomes of this novel program. PROCEDURE: Mentees selected mentors with
expertise in different subspecialties within the field from mentor profiles at
the ASPHO Web site. Of 23 enrolled pairs, 19 mentors and 16 mentees completed
electronic program feedback evaluations. The authors analyzed data collected
between February 2013 and December 2014. The authors used descriptive statistics
for categorical data and thematic analysis for qualitative data. RESULTS: The
overall response rate was 76% (35/46). At the initiation of the relationship,
career development and research planning were the most commonly identified goals
for both mentors and mentees. Participants communicated by phone, e-mail, or met
in-person at ASPHO annual meetings. Most mentor-mentee pairs were satisfied with
the mentoring relationship, considered it a rewarding experience that justified
their time and effort, achieved their goals in a timely manner with objective
work products, and planned to continue the relationship. However, time
constraints and infrequent communications remained a challenge. CONCLUSIONS:
Participation in the ASPHO mentoring program suggests a clear benefit to a broad
spectrum of ASPHO EC members with diverse personal and professional development
needs. Efforts to expand the mentoring program are ongoing and focused on
increasing enrollment of mentors to cover a wider diversity of career
tracks/subspecialties and evaluating career and academic outcomes more
objectively.
PMID- 27616580
TI - [The cerebellum as a major player in motor disturbances related to Autistic
Syndrome Disorders].
AB - SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental
disorders associated with disturbances in communication, social interactions,
cognition and affect. ASD are also accompanied by complex movement disorders,
including ataxia. A special focus of recent research in this area is made on the
striatum and the cerebellum, two structures known not only to control movement
but also to be involved in cognitive functions such as memory and language.
Dysfunction within the motor system may be associated with abnormal movements in
ASD that are translated into ataxia, abnormal pattern of righting, gait
sequencing, development of walking, and hand positioning. This line of study may
generate new knowledge and understanding of motor symptoms associated with ASD
and aims to deliver fresh perspectives for early diagnosis and therapeutic
strategies against ASD. AIMS OF THE REVIEW: Despite the relative paucity of
research in this area (compared to the social, linguistic, and behavioural
disturbances in ASD), there is evidence that the frontostriatal motor system
and/or the cerebellar motor systems may be the site of dysfunction in ASD.
Indeed, the cerebellum seems to be essential in the development of basic social
capabilities, communication, repetitive/restrictive behaviors, and motor and
cognitive behaviors that are all impaired in ASD. Cerebellar neuropathology
including cerebellar hypoplasia and reduced cerebellar Purkinje cell numbers are
the most consistent neuropathologies linked to ASD. The functional state of the
cerebellum and its impact on brain function in ASD is the focus of this review.
This review starts by recapitulating historical findings pointing towards an
implication of the cerebellum, and to a lesser extent the basal ganglia
structures, in TSA. We then detail the structure/function of the cerebellum at
the regional and cellular levels before describing human and animal findings
indicating a role of the cerebellum and basal ganglia in ASD. HUMAN AND ANIMAL
FINDINGS: Several studies have attempted to identify the nature of the motor
system dysfunction in ASD, and it became apparent that the motor fronto-striatal
and cerebellar systems are major sites of dysfunction in this psychiatric
illness. Anomalies in these structures have been revealed both at the anatomical
and functional levels in human patients as well as in animal models. These models
are obtained by manipulation of genes that are often implicated in glutamate
transmission, by lesions of brain structures among which the cerebellum, by
pharmacological treatment with drugs such as the Valproate or by maternal
infections with bacterial membrane extracts of double stranded RNA mimicking a
viral infection. CONCLUSION: The "cognitive approach" has dominated ASD research
for three decades and led to the design of interventional strategies, which have
yielded satisfactory results. Nevertheless, new approaches and alternative
hypotheses on the aetiology and diagnosis of ASD are needed. Research focused on
motor rather than psychiatric symptoms may have a greater potential to elucidate
the neurobiological basis of ASD.
PMID- 27616581
TI - Clinical predictors of shockable versus non-shockable rhythms in patients with
out-of-hospital cardiac arrest.
AB - AIM: To identify factors associated with a non-shockable rhythm as first recorded
heart rhythm. METHODS: Patients >=18 years old suffering out-of-hospital cardiac
arrest between 2001 and 2012 were identified in the population-based Danish
Cardiac Arrest Registry. Danish administrative registries were used to identify
chronic diseases (within 10 years) and drug prescriptions (within 180 days). A
multivariable logistic regression model, including patient related and cardiac
arrest related characteristics, was used to estimate odds ratios (OR) for factors
associated with non-shockable rhythm. RESULTS: A total of 29,863 patients were
included: 6600 (22.1%) patients with a shockable rhythm and 23,263 (77.9%)
patients with a non-shockable rhythm. A non-shockable rhythm was associated with
female gender, arrest in private home, unwitnessed arrest, no bystander CPR, and
longer time to first rhythm analysis compared to patients with shockable rhythm.
In the adjusted multivariable regression model, pre-existing non-cardiovascular
disease and drug prescription were associated with a non-shockable rhythm e.g.
chronic obstructive lung disease (OR 1.44 [95% CI: 1.32-1.58]); and the
prescription for antidepressants (OR 1.49 [95% CI: 1.35-1.65]), antipsychotics
(OR 2.30 [95% CI: 1.96-2.69]) analgesics (OR 1.32 [95% CI: 1.23-1.41]),
corticosteroids (OR 1.64 [95% CI: 1.44-1.85]), and antibiotics (OR 1.59 [95% CI:
1.40-1.81]). In contrast, the prescription of cardiovascular drugs and a history
of cardiovascular disease e.g. ischemic heart disease was associated with a lower
risk of non-shockable rhythm (OR 0.66 [95% CI: 0.60-0.71]). CONCLUSION: This
study demonstrate that non-cardiovascular disease and medication prescription are
associated with a non-shockable rhythm while cardiovascular disease and
medication prescription are associated with a shockable rhythm as first recorded
rhythm in patients with OHCA.
PMID- 27616579
TI - Rumination in migraine: Mediating effects of brooding and reflection between
migraine and psychological distress.
AB - OBJECTIVE: The relationship between migraine and psychological distress has been
consistently reported in cross-sectional and longitudinal studies. We
hypothesised that a stable tendency to perseverative thoughts such as rumination
would mediate the relationship between migraine and psychological distress.
Design and Main Outcomes Measures: Self-report questionnaires measuring
depressive rumination, current psychological distress and migraine symptoms in
two independent European population cohorts, recruited from Budapest (N = 1139)
and Manchester (N = 2004), were used. Structural regression analysis within
structural equation modelling was applied to test the mediational role of
brooding and reflection, the components of rumination, between migraine and
psychological distress. Sex, age and lifetime depression were controlled for in
the analysis. RESULTS: Migraine predicted higher brooding and reflection scores,
and brooding proved to be a mediator between migraine and psychological distress
in both samples, while reflection mediated the relationship significantly only in
the Budapest sample. CONCLUSIONS: Elevated psychological distress in migraine is
partially attributed to ruminative response style. Further studies are needed to
expand our findings to clinical samples and to examine how rumination links to
the adjustment to migraine.
PMID- 27616583
TI - Should physicians attend out-of-hospital cardiac arrests?
PMID- 27616582
TI - Cardiac arrest at the workplace: Results from an international survey about First
Aid on Red Cross and Red Crescent Societies and International Companies Network.
PMID- 27616584
TI - Diameter Dependence of Planar Defects in InP Nanowires.
AB - In this work, extensive characterization and complementary theoretical analysis
have been carried out on Au-catalyzed InP nanowires in order to understand the
planar defect formation as a function of nanowire diameter. From the detailed
transmission electron microscopic measurements, the density of stacking faults
and twin defects are found to monotonically decrease as the nanowire diameter is
decreased to 10 nm, and the chemical analysis clearly indicates the drastic
impact of In catalytic supersaturation in Au nanoparticles on the minimized
planar defect formation in miniaturized nanowires. Specifically, during the
chemical vapor deposition of InP nanowires, a significant amount of planar
defects is created when the catalyst seed sizes are increased with the lower
degree of In supersaturation as dictated by the Gibbs-Thomson effect, and an
insufficient In diffusion (or Au-rich enhancement) would lead to a reduced and
non-uniform In precipitation at the NW growing interface. The results presented
here provide an insight into the fabrication of "bottom-up" InP NWs with
minimized defect concentration which are suitable for various device
applications.
PMID- 27616585
TI - Microarray gene expression during early healing of GBR-treated calvarial critical
size defects.
AB - OBJECTIVES: To investigate the gene expression and molecular pathways implicated
in the regulation of the osseous healing process following guided bone
regeneration (GBR). MATERIAL AND METHODS: Six 6-month-old Wistar male rats were
used. Standardized 5-mm critical size defects were created in the parietal bones
of each animal and treated with an extracranial and intracranial ePTFE membrane,
according to the GBR principle. Three animals were randomly sacrificed after 7
and 15 days of healing. Total RNA was extracted from each sample and prepared for
gene expression analysis. RNA quality and quantity were assessed, followed by
hybridization of the cRNA to Affymetrix GeneChip Rat Genome 230 2.0 Arrays. The
Affymetrix data were processed, and first-order analysis, quality control and
statistical analysis were performed. Biological interpretation was performed via
pathway and Gene Ontology (GO) analysis. RESULTS: Between the 7- and 15-day
samples, 538 genes were differently regulated. At day 7, inflammatory and immune
responses were clearly upregulated. In addition, GO terms related to angiogenesis
and cell cycle regulation were overexpressed. At day 15, a more complex cellular
activity and cell metabolism were evident. The bone formation processes were
significantly overexpressed, with several genes encoding growth factors, enzyme
activity, and extracellular matrix formation found as upregulated. Remarkably, a
negative regulation of Wnt signalling pathway was observed at 15 days.
DISCUSSION: The gene expression profile of the cells participating in osseous
formation varied depending on the healing stage. A number of candidate genes that
seem differentially expressed during early stages of intramembranous bone
regeneration was suggested.
PMID- 27616587
TI - Innate immunity: IL-1beta activation under scrutiny.
PMID- 27616586
TI - Homogeneous diet of contemporary Japanese inferred from stable isotope ratios of
hair.
AB - The globalization of food production and distribution has homogenized human
dietary patterns irrespective of geography, but it is uncertain how far this
homogenization has progressed. This study investigated the carbon and nitrogen
isotope ratios in the scalp hair of 1305 contemporary Japanese and found values
of -19.4 +/- 0.60/00 and 9.4 +/- 0.60/00 (mean +/- SD), respectively. Within
Japan, the inter-regional differences for both isotope ratios was less than
10/00, which indicates low dietary heterogeneity among prefectural divisions. The
carbon and nitrogen isotope ratios of the hair showed a significant correlation
with the results of questionnaires on self-reported dietary habits. The carbon
isotope ratios from Japan were lower than those in samples from the USA but
higher than those in samples from Europe. These differences stem from the varying
dietary proportions of food products originally derived from C3 and C4 plants.
The dietary variation of Japan is as small as those of Europe and USA and smaller
than those of some Asian countries. These results indicate that dietary
homogeneity has progressed in Japan, which may indicate the influence from the
spread of the Western-style diet and food globalization, although dietary
heterogeneity among countries is still preserved.
PMID- 27616588
TI - Innate immune cells: A Morrbid way of stayin' alive.
PMID- 27616590
TI - Primed for success: Oyster parents treated with poly(I:C) produce offspring with
enhanced protection against Ostreid herpesvirus type I infection.
AB - The Pacific oyster (Crassostrea gigas) is farmed globally. Ostreid herpesvirus
(OsHV-1) causes severe mortalities of farmed C. gigas. Management of OsHV-1 has
proven difficult. Oysters treated with poly(I:C) exhibit enhanced protection (EP)
against OsHV-1. This chemical treatment is highly effective, but it is not
feasible to treat every oyster on a farm. To circumvent this practical
limitation, previous studies on arthropods have suggested that EP can be
transferred from parents to their offspring (trans-generational EP, TGEP). This
suggests that the treatment of relatively few parents could be used to produce
large numbers of offspring with TGEP. Here, we investigated TGEP in oysters to
test whether it might be used as a cost effective management tool to control OsHV
1. We found that offspring (D-veliger larvae) produced from poly(I:C)-treated
parents had double the chance of surviving exposure to OsHV-1 compared to
controls. Furthermore, the larvae of poly(I:C)-treated parents contained elevated
levels of mRNA encoding a key transcription factor that regulates antiviral
immunity (IRF2). Poly(I:C) treatment had no effect on the survival of oyster
parents. Hence, the enhanced immunity of their offspring could not be explained
by genetic selection, and instead may reflect epigenetic reprogramming or
maternal provisioning.
PMID- 27616591
TI - Growth charts for individuals with rhizomelic chondrodysplasia punctata.
AB - Rhizomelic chondrodysplasia punctata (RCDP) is a class of peroxisomal disorders
characterized by defective plasmalogen biosynthesis. There are multiple
recognized types of RCDP, all of which have autosomal recessive inheritance, and
their associated genes are known: RCDP type 1 with PEX7, RCDP type 2 with GNPAT,
RCDP type 3 with AGPS, RCDP type 4 with FAR1, and RCDP type 5 with PEX5. Among
other medical/developmental issues, plasmalogen deficiency has a direct effect on
bone growth and results in postnatal growth failure, the severity of which
corresponds to the degree of plasmalogen deficiency. In order to document growth
in patients with RCDP, we present detailed growth curves for length, weight, and
head circumference derived from retrospective data from 23 individuals with RCDP
types 1 and 2 confirmed by molecular and/or biochemical studies. We stratified
growth curves by age as well as by plasmalogen level, with those with higher
plasmalogens grouped as "non-classic." The growth charts presented here provide
guidance to families and physician caretakers on the natural course of growth in
individuals with RCDP during infancy into early childhood, and thus will have
particular utility in setting expectations and guiding optimal feeding
interventions in this population.(c) 2016 Wiley Periodicals, Inc.
PMID- 27616589
TI - PI3Kdelta and primary immunodeficiencies.
AB - Primary immunodeficiencies are inherited disorders of the immune system, often
caused by the mutation of genes required for lymphocyte development and
activation. Recently, several studies have identified gain-of-function mutations
in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110delta)
and PIK3R1 (which encodes p85alpha) that cause a combined immunodeficiency
syndrome, referred to as activated PI3Kdelta syndrome (APDS; also known as
p110delta-activating mutation causing senescent T cells, lymphadenopathy and
immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of
function mutations that affect these genes lead to immunosuppression, albeit via
different mechanisms. Here, we review the roles of PI3Kdelta in adaptive
immunity, describe the clinical manifestations and mechanisms of disease in APDS
and highlight new insights into PI3Kdelta gleaned from these patients, as well as
implications of these findings for clinical therapy.
PMID- 27616594
TI - Impedance Threshold Device Combined With High-Quality Cardiopulmonary
Resuscitation Improves Survival With Favorable Neurological Function After
Witnessed Out-of-Hospital Cardiac Arrest.
AB - BACKGROUND: The quality of cardiopulmonary resuscitation (CPR) has been recently
shown to affect clinical outcome. The Resuscitation Outcomes Consortium (ROC)
Prehospital Resuscitation Impedance Valve and Early Versus Delayed Analysis
(PRIMED) trial showed no differences in outcomes with an active vs. sham
impedance threshold device (ITD), a CPR adjunct that enhances circulation. It was
hypothesized the active ITD would improve survival with favorable neurological
outcomes in witnessed out-of-hospital cardiac arrest patients when used with high
quality CPR. METHODS AND RESULTS: Using the publicly accessible ROC PRIMED
database, a post-hoc analysis was performed on all witnessed subjects with both
compression rate and depth data (n=1,808) who received CPR within the study
protocol definition of adequate CPR quality (compression rate 80-120/min and
depth 4-6 cm; n=929). Demographics were similar between sham and active ITD
groups. In witnessed subjects who received quality CPR, survival with favorable
neurological function was 11.9% for the active ITD subjects (56/470) vs. 7.4% for
the sham (34/459) (odds ratio 1.69 [95% confidence interval 1.08, 2.64]). There
were no statistically significant differences for this primary outcome when CPR
was performed outside the boundaries of the definition of adequate CPR quality.
Multivariable models did not change these associations. CONCLUSIONS: An active
ITD combined with adequate-quality conventional CPR has the potential to
significantly improve survival after witnessed cardiac arrest. (Circ J 2016; 80:
2124-2132).
PMID- 27616592
TI - Emerging integrated nanoclay-facilitated drug delivery system for papillary
thyroid cancer therapy.
AB - Nanoclay can be incorporated into emerging dual functional drug delivery systems
(DDSs) to promote efficiency in drug delivery and reduce the toxicity of
doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the
expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to
0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin
molecules and controlling the diffusion rate. A targeted design for papillary
thyroid cancer cells was achieved by introducing KI, which is consumed by the
sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser
scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite
(KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer
cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in
vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic
drug. Furthermore, active and passive targeting strategies played a role in the
accumulation of the drug molecules, as verified by an in vivo bio-distribution
analysis.
PMID- 27616595
TI - Optical Coherence Tomography for Online Guidance of Complex Coronary
Interventions.
AB - Decision making on lesion preparation and stent/scaffold optimization are
cornerstones of patient outcome. Intravascular imaging recently emerged as a
critical modality to achieve better results of stent/scaffold implantation and
superior clinical outcomes compared with coronary angiography alone. Optical
coherence tomography (OCT), a light-based intravascular imaging modality with
high frame rate in acquisition and very high speed pullback, can interrogate the
target vessel in a couple of seconds, and immediately display a pristine
longitudinal lumen contour with automatic detection of lesion severity, site and
lumen/stent areas. Further, OCT provides pivotal information on sites of calcium,
with accurate measurements of the minimum distance from the lumen, a major
determinant of stent/scaffold underexpansion, malapposition and eccentricity.
Finally, to guide the PCI procedure using OCT without operator misjudgment, a
real-time point-to-point correspondence between angiographic and OCT images has
been recently created. Co-registration of OCT with angiography with direct
tableside control of acquisition and analysis enables the operator to plan and
map optimal stent/scaffold implantation. To prove the clinical relevance of OCT
guided PCI, simple, standardized interventional planning, including pre- and
postprocedural automatic lumen detection metrics, has to be translated into
effective treatment flow algorithms. A similar OCT algorithm is being tested in
the ongoing prospective, randomized, multicenter ILUMIEN III study, to
demonstrate that OCT-guided stent placement is superior to angiography-guided and
non-inferior to IVUS-guided stent implantation. (Circ J 2016; 80: 2063-2072).
PMID- 27616593
TI - Interpretation of the evidence for the efficacy and safety of statin therapy.
AB - This Review is intended to help clinicians, patients, and the public make
informed decisions about statin therapy for the prevention of heart attacks and
strokes. It explains how the evidence that is available from randomised
controlled trials yields reliable information about both the efficacy and safety
of statin therapy. In addition, it discusses how claims that statins commonly
cause adverse effects reflect a failure to recognise the limitations of other
sources of evidence about the effects of treatment. Large-scale evidence from
randomised trials shows that statin therapy reduces the risk of major vascular
events (ie, coronary deaths or myocardial infarctions, strokes, and coronary
revascularisation procedures) by about one-quarter for each mmol/L reduction in
LDL cholesterol during each year (after the first) that it continues to be taken.
The absolute benefits of statin therapy depend on an individual's absolute risk
of occlusive vascular events and the absolute reduction in LDL cholesterol that
is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an
effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about L2
per month) for 5 years in 10 000 patients would typically prevent major vascular
events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre
existing occlusive vascular disease (secondary prevention) and in 500 patients
(ie, 5% absolute benefit) who are at increased risk but have not yet had a
vascular event (primary prevention). Statin therapy has been shown to reduce
vascular disease risk during each year it continues to be taken, so larger
absolute benefits would accrue with more prolonged therapy, and these benefits
persist long term. The only serious adverse events that have been shown to be
caused by long-term statin therapy-ie, adverse effects of the statin-are myopathy
(defined as muscle pain or weakness combined with large increases in blood
concentrations of creatine kinase), new-onset diabetes mellitus, and, probably,
haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an
effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of
myopathy (one of which might progress, if the statin therapy is not stopped, to
the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes, and 5
10 haemorrhagic strokes. However, any adverse impact of these side-effects on
major vascular events has already been taken into account in the estimates of the
absolute benefits. Statin therapy may cause symptomatic adverse events (eg,
muscle pain or weakness) in up to about 50-100 patients (ie, 0.5-1.0% absolute
harm) per 10 000 treated for 5 years. However, placebo-controlled randomised
trials have shown definitively that almost all of the symptomatic adverse events
that are attributed to statin therapy in routine practice are not actually caused
by it (ie, they represent misattribution). The large-scale evidence available
from randomised trials also indicates that it is unlikely that large absolute
excesses in other serious adverse events still await discovery. Consequently, any
further findings that emerge about the effects of statin therapy would not be
expected to alter materially the balance of benefits and harms. It is, therefore,
of concern that exaggerated claims about side-effect rates with statin therapy
may be responsible for its under-use among individuals at increased risk of
cardiovascular events. For, whereas the rare cases of myopathy and any muscle
related symptoms that are attributed to statin therapy generally resolve rapidly
when treatment is stopped, the heart attacks or strokes that may occur if statin
therapy is stopped unnecessarily can be devastating.
PMID- 27616596
TI - "Hamstring Leaflet" Now Demonstrated to Be a Determinant of Functional Mitral
Regurgitation in Patients With Atrial Fibrillation.
PMID- 27616598
TI - Antinuclear autoantibodies and pregnancy outcome in women with unexplained
recurrent miscarriage.
AB - PROBLEM: To investigate whether antinuclear autoantibodies (ANA) could be related
to the outcome of the successive pregnancy in women with unexplained recurrent
miscarriage (uRM). METHODS: Circulating ANA were measured by indirect
immunofluorescence in 86 women with uRM before pregnancy, repeated in the first
trimester of the successive gestation and correlated with pregnancy outcome.
RESULTS: Forty-one women were ANA- and 45 were ANA+ before pregnancy. No relation
was found between pre-pregnancy ANA status and the outcome of the successive
pregnancy. However, when these women were monitored at 7th week during their
pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages
(31.8%) were observed, whereas all of the 23 ANA+ women who became ANA- had
pregnancies ongoing beyond the 20th week without miscarriage. CONCLUSIONS: ANA
status could have a role in uRM. Disappearance of ANA in early pregnancy could
have a favorable prognostic value in the successive pregnancy.
PMID- 27616597
TI - Effects of allergic diseases and age on the composition of serum IgG glycome in
children.
AB - It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic
reactions. The glycans on the Fc region are known to affect IgG effector
functions, thereby possibly having a role in IgG modulation of allergic response.
This is the first study investigating patients' IgG glycosylation profile in
allergic diseases. Subclass specific IgG glycosylation profile was analyzed in
two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children
(conducted at University of Aberdeen, UK and Children's Hospital Srebrnjak,
Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma
by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed
by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb
cohort IgG glycome composition changed with age across all IgG subclasses. In
both cohorts, IgG glycome composition did not differ in allergen sensitized
subjects, nor children sensitized to individual allergens, single allergen mean
wheal diameter or positive wheal sum values. In the Zagreb study the results were
also replicated for high total serum IgE and in children with self-reported
manifest allergic disease. In conclusion, our findings demonstrate no association
between serum IgG glycome composition and allergic diseases in children.
PMID- 27616599
TI - Relationship between grip strength and newly diagnosed nonalcoholic fatty liver
disease in a large-scale adult population.
AB - Enhanced muscle strength is often related to improved insulin sensitivity and
secretion, control of lipid metabolism, and increased secretion of myokines.
These factors have emerged as important mechanisms involved in the development
and progression of nonalcoholic fatty liver disease (NAFLD), implying that muscle
strength may be a useful predictor for NAFLD. We aimed to assess the relationship
between grip strength (GS) and NAFLD in a large-scale adult population. GS was
assessed using an electronic hand-grip dynamometer, and NAFLD was diagnosed by
the liver ultrasonography. Multiple logistic regression analysis was used to
assess the relationship between the quartiles of GS per body weight and the
prevalence of NAFLD. After adjusting for potentially confounding factors, the
odds ratios (95% confidence interval) for overall NAFLD, NAFLD with normal
alanine aminotransferase levels, and NAFLD with elevated alanine aminotransferase
levels across the quartiles of GS were 1.00 (reference), 0.89 (0.78, 1.01), 0.77
(0.67, 0.89), and 0.67 (0.57, 0.79); 1.00 (reference), 0.91 (0.80, 1.04), 0.79
(0.68, 0.92), and 0.72 (0.61, 0.85); 1.00 (reference), 0.77 (0.61, 0.98), 0.67
(0.51, 0.86), and 0.53 (0.40, 0.71) (all P for trend < 0.01), respectively. This
is the first study shows that increased GS is independently associated with lower
prevalence of NAFLD.
PMID- 27616602
TI - Corrigendum: A metabolic profile in Ruditapes philippinarum associated with
growth-promoting effects of alginate hydrolysates.
PMID- 27616601
TI - Common variants of HTR3 genes are associated with obsessive-compulsive disorder
and its phenotypic expression.
AB - Evidence from literature supports the existence of associations between serotonin
related genetic variants and obsessive-compulsive disorder (OCD), but few studies
have explored the involvement of serotonin receptor type 3 genes (HTR3) in OCD.
To identify whether HTR3 variability affects an individual's susceptibility to
OCD, we examined 10 HTR3 variants in 596 individuals with OCD and 599 controls. A
significant difference existed in the genotypic distribution of the HTR3B variant
rs1176744 between individuals with OCD and controls (odds ratio [OR] = 0.74, 95%
confidence interval [CI] = 0.60-0.91, P = 0.0043). A protective haplotype in
HTR3B was also associated with OCD (OR = 0.77, CI = 0.63-0.95, permutated P =
0.0179). Analyses of OCD sub-phenotypes demonstrated significant associations
between rs3758987 and early onset OCD in male subjects (OR = 0.49, CI = 0.31
0.79, P = 0.0031) and among rs6766410, rs6443930, and the cleaning dimension in
female subjects (OR = 0.36, CI = 0.18-0.69, P = 0.0016 and OR = 0.47, CI = 0.29
0.79, P = 0.0030, respectively). Additionally, rs6766410 was related to
contamination-based disgust in OCD (P = 0.0044). These results support that
common HTR3 variants are involved in OCD and some of its clinical phenotypes.
PMID- 27616600
TI - Third-world realities in a first-world setting: A study of the HIV/AIDS-related
conditions and risk behaviors of sex trade workers in Saskatoon, Saskatchewan,
Canada.
AB - The transmission and prevalence of Human Immunodeficiency Virus (HIV) among those
employed as sex trade workers (STW) is a major public health concern. The present
study describes the self-reported responses of 340 STW, at-risk for contracting
HIV. The participants were recruited by selective targeting between 2009 and 2010
from within the Saskatoon Health Region (SHR), Saskatchewan, Canada. As of 2012,
the SHR has the highest incidence rate of positive test reports for HIV in
Canada, at more than three times the national average (17.0 vs. 5.9 per 100,000
people). Additionally, the epidemiology of HIV/AIDS in the SHR is different from
that seen elsewhere in Canada (still mostly men having sex with men and
Caucasians), with its new HIV cases predominantly associated with injection drug
use and Aboriginal cultural status. The purpose of this study was to (a) describe
the demographic and socio-economic characteristics of the STW in the SHR, (b)
identify their significant life events, self-reported problems, knowledge,
attitudes, behaviors, self-efficacy, and barriers regarding HIV, and (c)
determine the significant independent risk indicators for STW self-reporting a
chance of greater than 50% of becoming infected with HIV/AIDS. The majority of
the study participants were females, who were never married, of Aboriginal
descent, without a high school diploma, and had an annual income of less than
$10,000. Using multivariate regression analysis, four significant independent
risk indicators were associated with STW reporting a greater that 50% chance of
acquiring HIV/AIDS, including experiencing sexual assault as a child, injecting
drugs in the past four weeks, being homeless, and a previous Chlamydia diagnosis.
These findings provide important evidence of the essential sexual and drug
related vulnerabilities associated with the risk of HIV infection among STW and
offer insight into the design and implementation of effective and culturally
sensitive public health intervention and prevention efforts. To be most
effective, it is recommended that such intervention and prevention initiatives:
(1) use specifically tailored community-based outreach to high risk STW who are
drug users and link them with appropriate drug treatment and HIV/AIDS prevention
and treatment services, (2) provide free and confidential, routine HIV counseling
and testing in substance abuse programs, and (3) build capacity among the local,
Aboriginal NGOs so as to address with cultural sensitivity both the drug and HIV
related risk factors prevalent among this vulnerable population.
PMID- 27616603
TI - Howard Y. Chang: 'Lnc'-ing Junk to Disease.
PMID- 27616604
TI - Visual reporters for study of the osteoblast lineage.
AB - Advancing our understanding of osteoblast biology and differentiation is critical
to elucidate the pathological mechanisms responsible for skeletal diseases such
as osteoporosis. Histology and histomorphometry, the classical methods to study
osteoblast biology, identify osteoblasts based on their location and morphology
and ability to mineralize matrix, but do not clearly define their stage of
differentiation. Introduction of visual transgenes into the cells of osteoblast
lineage has revolutionized the field and resulted in a paradigm shift that
allowed for specific identification and isolation of subpopulations within the
osteoblast lineage. Knowledge acquired from the studies based on GFP transgenes
has allowed for more precise interpretation of studies analyzing targeted
overexpression or deletion of genes in the osteoblast lineage. Here, we provide a
condensed overview of the currently available promoter-fluorescent reporter
transgenic mice that have been generated and evaluated to varying extents. We
cover different stages of the lineage as transgenes have been utilized to
identify osteoprogenitors, pre-osteoblasts, osteoblasts, or osteocytes. We show
that each of these promoters present with advantages and disadvantages. The
studies based on the use of these reporter mice have improved our understanding
of bone biology. They constitute attractive models to target osteoblasts and help
to understand their cell biology.
PMID- 27616605
TI - Assessing the general population frequency of rare coding variants in the EXT1
and EXT2 genes previously implicated in hereditary multiple exostoses.
AB - Hereditary multiple exostoses (HME) is a rare childhood-onset skeletal disease
linked to mutations in exostosin glycosyltransferase 1 (EXT1) or 2 (EXT2).
Patients are heterozygous for either an EXT1 or EXT2 mutation, and it is widely
assumed that exostosis formation and associated defects, such as growth
retardation and skeletal deformities, require loss-of-heterozygosity or a second
hit in affected cells. However, the relevance and phenotypic impact of many
presumed pathogenic EXT variants remain uncertain. We extracted all amino acid
altering (missense) and loss of function (LoF; nonsense, frameshift, or splice
site) variants from the Exome Aggregation Consortium (ExAC), a large population
based repository of exome sequence data from diverse ancestries that has screened
out severe pediatric disease, to assess the overall mutation spectrum of
predicted protein-damaging variants across these two genes in the general
population. We then determined whether clinically-identified, presumably
pathogenic variants implicated in HME exist among healthy individuals. We found
six EXT1 and four EXT2 missense mutations in ExAC, suggesting that these
mutations have either been misclassified as pathogenic or are not fully
penetrant. Furthermore, EXT1 is heavily selectively constrained, while EXT2 is
more tolerant to protein-damaging variants, especially at its C-terminus,
possibly explaining the genotype-phenotype correlation that EXT1 variants usually
result in more severe disease. In conclusion, population-based exome data is a
useful filter for determining whether clinically detected variants are likely
pathogenic, as well as revealing biological insight into rare disease genes such
as EXT1 and EXT2.
PMID- 27616606
TI - The Burden of Bladder Pain in Five European Countries: A Cross-sectional Study.
AB - OBJECTIVE: To estimate the burden of illness associated with bladder pain in 5
European countries: France, Germany, Italy, Spain, and the United Kingdom.
PATIENTS AND METHODS: Patients with a diagnosis of bladder pain (ie, unpleasant
sensation, pain, pressure, or discomfort related to the urinary bladder) were
identified from data collected by the cross-sectional National Health and
Wellness Survey performed in 2013. Propensity score matching was used to
construct a comparator group without bladder pain (1 case: 2 controls).
Assessments were performed for several outcomes including health-related quality
of life (HRQoL; 36-item Short-Form, version 2), work-related function (Work
Productivity and Activity Impairment questionnaire), employment status, and all
cause healthcare resource use. RESULTS: We identified 275 patients with a
physician diagnosis of bladder pain, 274 of whom were successfully matched to 548
controls without bladder pain. Compared with matched controls, patients with
bladder pain had significantly impaired HRQoL (mental component summary: 38.5 vs
44.5; physical component summary: 38.9 vs 47.8; P <.001). Overall work
productivity loss was significantly greater in patients with bladder pain
compared with matched controls (41.7% vs 21.5%; P <.001). Patients with bladder
pain were also significantly more likely to use all-cause healthcare resources
and make more visits to healthcare providers in the previous 6 months than
matched controls (P <.001 for all outcomes). CONCLUSION: Bladder pain is
associated with a considerable burden in Europe in terms of impaired HRQoL and
work productivity, and increased healthcare resource use.
PMID- 27616607
TI - Feasibility and Safety of a Virtual Reality Dodgeball Intervention for Chronic
Low Back Pain: A Randomized Clinical Trial.
AB - : Whereas the fear-avoidance model of chronic low back pain (CLBP) posits a
generic avoidance of movement that is perceived as threatening, we have
repeatedly shown that individuals with high fear and CLBP specifically avoid
flexion of the lumbar spine. Accordingly, we developed a virtual dodgeball
intervention designed to elicit graded increases in lumbar spine flexion while
reducing expectations of fear and harm by engaging participants in a competitive
game that is entertaining and distracting. We recruited 52 participants (48%
female) with CLBP and high fear of movement and randomized them to either a game
group (n = 26) or a control group (n = 26). All participants completed a pregame
baseline and a follow-up assessment (4-6 days later) of lumbar spine motion and
expectations of pain and harm during standardized reaches to high (easier),
middle, and low (hardest to reach) targets. For 3 consecutive days, participants
in the game group completed 15 minutes of virtual dodgeball between baseline and
follow-up. For the standardized reaching tests, there were no significant effects
of group on changes in lumbar spine flexion, expected pain, or expected harm.
However, virtual dodgeball was effective at increasing lumbar flexion within and
across gameplay sessions. Participants reported strong positive endorsement of
the game, no increases in medication use, pain, or disability, and no adverse
events. Although these findings indicate that very brief exposure to this game
did not translate to significant changes outside the game environment, this was
not surprising because graded exposure therapy for fear of movement among
individuals with low back pain typically last 8 to 12 sessions. Because of the
demonstration of safety, feasibility, and ability to encourage lumbar flexion
within gameplay, these findings provide support for a clinical trial wherein the
treatment dose is more consistent with traditional graded exposure approaches to
CLBP. PERSPECTIVE: This study of a virtual reality dodgeball intervention
provides evidence of feasibility, safety, and utility to encourage lumbar spine
flexion among individuals with CLBP and high fear of movement.
PMID- 27616609
TI - Nance-Horan syndrome-The oral perspective on a rare disease.
AB - The present study describes seven patients with Nance-Horan syndrome, all
referred to a specialized oral care unit in the Central Denmark Region. A
literature search on "Nance Horan Syndrome" resulted in 53 publications among
which 29 reported on dental findings. Findings reported in these papers have been
systematized to obtain an overview of the reported findings and the terminology
on dental morphology. All seven patients included in the present study showed
deviations of crown morphology on incisors and/or molars. The only consistent and
very clear dental aberration was alterations in the tooth morphology that is
screwdriver-shaped incisors and bud molars being most pronounced in the permanent
dentition, but were also present in the primary dentition. In addition, three
patients had supernumerary teeth, and three had dental agenesis. In conclusion, a
dental examination as a part of the diagnostic process may reveal distinct
characteristics of the dental morphology, which could be of diagnostic value and
facilitate an early diagnosis. In the description of molar morphology in NHS
patients, it is recommended to use the term "bud molar." The combination of
congenital cataract, screwdriwer-shaped incisors and bud-shaped molars is a
strong clinical indication of Nance-Horan syndrome. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27616608
TI - Preserved Capacity for Placebo Analgesia in the Elderly.
AB - : The prevalence of chronic pain rises with increasing age. It has been suggested
that the mechanisms responsible for the development of chronic pain overlap with
mechanisms involved in aging, potentially implicating age-related changes in
descending modulatory pathways. This observation raises the question whether
other forms of endogenous pain modulation, in particular placebo analgesia,
become compromised with age. Because of the known contribution of placebo effects
to analgesic treatment outcomes this question is of important clinical relevance.
In this study, we compared the response to thermal painful stimuli and the
capacity for endogenous pain modulation between younger and older adults using a
well established placebo analgesia paradigm involving expectancy and conditioning
components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard
error of the mean +/- .61) and 24 older adults (60-80 years, mean = 69.3,
standard error of the mean +/- .89). We observed increased heat pain thresholds
and higher pain intensity ratings (in response to physically identical heat
stimulation) in the older compared with the younger group. However, the placebo
analgesic response was comparable between both age groups of healthy
participants. The preserved capacity for placebo analgesia in our sample of older
participants highlights the potential to use nonpharmacological analgesic
treatment strategies in this age group and to exploit placebo mechanisms as an
add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE:
In contrast to the commonly shared view that endogenous pain modulation declines
with age we found a comparable capacity for placebo analgesia in a group of
healthy older and younger adults.
PMID- 27616610
TI - [Innovative technology and blood safety].
AB - If technological innovations are not enough alone to improve blood safety, their
contributions for several decades in blood transfusion are major. The improvement
of blood donation (new apheresis devices, RFID) or blood components (additive
solutions, pathogen reduction technology, automated processing of platelets
concentrates) or manufacturing process of these products (by automated processing
of whole blood), all these steps where technological innovations were
implemented, lead us to better traceability, more efficient processes, quality
improvement of blood products and therefore increased blood safety for blood
donors and patients. If we are on the threshold of a great change with the
progress of pathogen reduction technology (for whole blood and red blood cells),
we hope to see production of ex vivo red blood cells or platelets who are real
and who open new conceptual paths on blood safety.
PMID- 27616611
TI - [Use of thrombelastography to guide posttraumatic hemostatic therapy: More
coagulation factor concentrates and less allogenic blood transfusion?]
AB - Viscoelastic technics are used for 10 years and include the ROTEM(r) and the
TEG(r). These devices that exploit the viscoelastic properties of the clotting
blood, allow a rapid and global analysis of the haemostatic process taking into
account all the process interfering with haemostasis such as inflammation. It has
been shown that the use of these technics in clinical situations such as trauma,
postpartum haemorrhage, gastrointestinal bleeding or cardiac surgery may reduce
the need for blood product, the cost and perhaps may improve the outcome of the
patients. Thanks to a rapid identification of the underlying coagulation deficit,
these technics facilitate decision-making during acute care and help to guide the
treatment, particularly with coagulation factor's concentrate.
PMID- 27616612
TI - Neuro-oncology: a selected review of ASCO 2016 abstracts.
AB - ASCO 2016, 29 May-2 June 2016, Chicago, IL, USA The largest annual clinical
oncology conference the American Society of Clinical Oncology is held in the USA
and gives researchers and other key opinion leaders the opportunity to present
new cancer clinical trials and research data. The CNS tumors section of the
American Society of Clinical Oncology 2016 covered various aspects of neuro
oncology including metastatic CNS diseases and primary brain tumors, presented
via posters, oral talks and over 100 abstracts. This brief review selectively
highlights presentations from this meeting in an organizational manner that
reflects clinically relevant aspects of a large and multifaceted meeting.
PMID- 27616614
TI - Anatomopathological changes of the cardiac conduction system in sudden cardiac
death, particularly in infants: advances over the last 25 years.
AB - Sudden cardiac death (SCD) is defined as the unexpected death without an obvious
noncardiac cause that occurs within 1 h of witnessed symptom onset (established
SCD) or within 24 h of unwitnessed symptom onset (probable SCD). In the United
States, its incidence is 69/100,000 per year. Dysfunctions of the cardiac
conduction and autonomic nervous systems are known to contribute to SCD
pathogenesis, even if most clinicians and cardiovascular pathologists lack
experience with detailed examination of the cardiac conduction system and fail to
recognize lesions that are crucial to explain the SCD itself. In this review, we
sought to describe the advances over the last 25 years in the study of the
anatomopathological changes of the conducting tissue, in SCD, in mature hearts
and particularly in sudden infant death syndrome (SIDS) and sudden intrauterine
unexpected death syndrome (SIUDS), through the articles published in our journal
Cardiovascular Pathology (CVP). We carried out an extensive Medline search to
retrieve and review all articles published in CVP in which the sudden unexpected
death of one or more subjects believed healthy was reported, especially if
associated with lesions of the conducting tissue in settings that revealed no
other explained causes of death, particularly in infants and fetuses. The cardiac
conduction findings of resorptive degeneration, His bundle dispersion, Mahaim
fibers, cartilaginous meta-hyperplasia, persistent fetal dispersion, left-sided
His bundle, septation of the bifurcation, atrioventricular node dispersion, sinus
node hypoplasia, Zahn node, His bundle hypoplasia, atrioventricular node, and His
bundle dualism were similarly detected in SIDS and SIUDS victims.
PMID- 27616613
TI - Paraffin processing of stented arteries using a postfixation dissolution of
metallic and polymeric stents.
AB - Studying the morphology of the arterial response to endovascular stent
implantation requires embedding the explanted stented artery in rigid materials
such as poly(methyl methacrylate) to enable sectioning through both the in situ
stent and the arterial wall, thus maintaining the proper anatomic relationships.
This is a laborious, time-consuming process. Moreover, the technical quality of
stained plastic sections is typically suboptimal and, in some cases, precludes
immunohistochemical analysis. Here we describe a novel technique for dissolution
of metallic and plastic stents that is compatible with subsequent embedding of
"destented" arteries in paraffin, fine sectioning, major staining protocols, and
immunohistochemistry.
PMID- 27616615
TI - Onset of a hypotensive effect following ingestion of flavan 3-ols involved in the
activation of adrenergic receptors.
AB - A lot of epidemiological and intervention studies support the hypotensive action
resulting from ingestion of foods rich in flavan 3-ols. However, the mechanisms
of this action remain unclear. We have reported previously on the alteration of
the micro- and systemic circulations after administration of a flavan 3-ol
fraction (FL) derived from cocoa in mammals. We also confirmed that blood
catecholamine levels increase significantly after administration of FL. In the
present study, we examined whether adrenaline receptors are involved in the
hemodynamic changes using several adrenaline receptor (AR) blockers. First, we
confirmed that mean blood pressure (MBP) decreased significantly and aortic
endothelial nitric oxide synthase (eNOS) levels increased significantly following
oral treatment of 10mg/kg FL for 2 weeks in normal rats compared with vehicle
administration. However, these changes were not observed with treatment of 1mg/kg
(-)-epicatechin (EC), which contains nearly equivalent amount of 10mg/kg FL.
Secondly, we observed that a single dose of FL produced different hemodynamic
changes, such as a transient elevation in heart rate (HR) after ingestion of 1
100mg/kg FL, but not with 1mg/kg EC. Furthermore, although MBP rose transiently
after 1 and 10mg/kg FL, this effect was not observed with 100mg/kg or 1mg/kg EC.
The increases in HR, MBP, and aortic phosphorylated eNOS (p-eNOS) induced by
10mg/kg FL were prevented completely by pretreatment with the AR blocker,
carvedilol. Combination treatment with 100mg/kg FL and an alpha1AR blocker,
prazosin, significantly reduced MBP, whereas the elevation in HR was enhanced. In
addition, after pretreatment with the beta2AR blocker, butoxamine, we observed no
significant hemodynamic changes with or without 100mg/kg FL. Moreover, the
combination of 100mg/kg FL and the alpha2AR blocker, yohimbine, markedly
increased MBP, HR and aortic p-eNOS level. These results suggested that the
postprandial hemodynamic changes after a single oral dose of FL were induced by
an adrenergic effect. This adrenomimetic activity suggested the involvement of a
hypotensive effect of FL.
PMID- 27616616
TI - And the survey said.... evaluating rationale for participation in gun buybacks as
a tool to encourage higher yields.
AB - BACKGROUND: Gun buyback programs represent one arm of a multipronged approach to
raise awareness and education about gun safety. METHODS: The city of Worcester,
MA has conducted an annual gun buyback at the Police Department Headquarters
since 2002. We analyzed survey responses from a voluntary, 18-question, face-to
face structured interview from December 2009 to June 2015 using descriptive
statistics to determine participant demographics and motivations for
participation. RESULTS: A total of 943 guns were collected, and 273 individuals
completed surveys. The majority of participants were white males older than
55years (42.4%). Participants represented 61 zip codes across Worcester County,
with 68% having prior gun safety training and 61% with weapons remaining in the
home (27% of which children could potentially access). The top reasons for
turning in guns were "no longer needed" (48%) and "fear of children accessing the
gun" (14%). About 1 in 3 respondents knew someone injured/killed by gun violence.
Almost all (96%) respondents claimed the program raised community awareness of
firearm risk. CONCLUSION: The Worcester Goods for Guns Buyback has collected more
than 900 guns between 2009 and 2015. The buyback removes unwanted guns from homes
and raises community awareness about firearm safety.
PMID- 27616617
TI - Categorization and repair of recurrent and acquired tracheoesophageal fistulae
occurring after esophageal atresia repair.
AB - PURPOSE: Recurrent trachea-esophageal fistula (recTEF) is a frequent (5%-10%)
complication of congenital TEF (conTEF) and esophageal atresia (EA) repair. In
addition, postoperative acquired TEF (acqTEF) can occur in addition to or even in
the absence of prior conTEF in the setting of esophageal anastomotic
complications. Reliable repair often proves difficult by endoluminal or standard
surgical techniques. We present the results of an approach that reliably
identifies the TEF and facilitates airway closure as well as repair of associated
tracheal and esophageal problems. METHODS: Retrospective review of 66 consecutive
patients 2009-2016 (55 referrals and 11 local) who underwent repair via
reoperative thoracotomy or cervicotomy for recTEF and acqTEF (IRB P00004344). Our
surgical approach used complete separation of the airway and esophagus, which
reliably revealed the TEF (without need for cannulation) and freed the tissues
for primary closure of the trachea and frequently resection of the tracheal
diverticulum. For associated esophageal strictures, stricturoplasty or resection
was performed. Separation of the suture lines by rotational pexy of the both
esophagus and the trachea, and/or tissue interposition were used to further
inhibit re-recurrence. For associated severe tracheomalacia, posterior
tracheopexy to the anterior spinal ligament was utilized. RESULTS: The TEFs were
recurrent (77%), acquired from esophageal leaks (26%), in addition to persistent
or missed H-type (6%). Seven patients in this series had multiple TEFs of more
than one category. Of the acqTEF cases, 6 were esophagobronchial, 10
esophagopulmonic, 2 esophagotracheal (initial pure EA cases), and 2 from a
gastric conduit to the trachea. Upon referral, 18 patients had failed endoluminal
treatments; and open operations for recTEF had failed in 18 patients. Significant
pulmonary symptoms were present in all. During repairs, 58% were found to have a
large tracheal diverticulum, and 51% had posterior tracheopexy for significant
tracheomalacia. For larger esophageal defects, 32% were treated by
stricturoplasty and 37% by segmental resection. Rotational pexy of the trachea
and/or esophagus was utilized in 62% of cases to achieve optimal suture line
separation. Review with a mean follow-up of 35months identified no recurrences,
and resolution of pulmonary symptoms in all. Stricture treatment required
postoperative dilations in 30, and esophageal replacement in 6 for long
strictures. There was one death. CONCLUSION: This retrospective review of 66
patients with postoperative recurrent and acquired TEF following esophageal
atresia repair is the largest such series to date and provides a new
categorization for postoperative TEF that helps clarify the diagnostic and
therapeutic challenges for management.
PMID- 27616618
TI - Fast detection of leaf pigments and isoprenoids for ecophysiological studies,
plant phenotyping and validating remote-sensing of vegetation.
AB - Rapid developments in remote-sensing of vegetation and high-throughput precision
plant phenotyping promise a range of real-life applications using leaf optical
properties for non-destructive assessment of plant performance. Use of leaf
optical properties for assessing plant performance requires the ability to use
photosynthetic pigments as proxies for physiological properties and the ability
to detect these pigments fast, reliably and at low cost. We describe a simple and
cost-effective protocol for the rapid analysis of chlorophylls, carotenoids and
tocopherols using high-performance liquid chromatography (HPLC). Many existing
methods are based on the expensive solvent acetonitrile, take a long time or do
not include lutein epoxide and alpha-carotene. We aimed to develop an HPLC method
which separates all major chlorophylls and carotenoids as well as lutein epoxide,
alpha-carotene and alpha-tocopherol. Using a C30 -column and a mobile phase with
a gradient of methanol, methyl-tert-butyl-ether (MTBE) and water, our method
separates the above pigments and isoprenoids within 28 min. The broad
applicability of our method is demonstrated using samples from various plant
species and tissue types, e.g. leaves of Arabidopsis and avocado plants, several
deciduous and conifer tree species, various crops, stems of parasitic dodder,
fruit of tomato, roots of carrots and Chlorella algae. In comparison to previous
methods, our method is very affordable, fast and versatile and can be used to
analyze all major photosynthetic pigments that contribute to changes in leaf
optical properties and which are of interest in most ecophysiological studies.
PMID- 27616619
TI - Reporting multiple cycles in trials on medically assisted reproduction.
AB - Trials assessing effectiveness in medically assisted reproduction (MAR) should
aim to study the desired effect over multiple cycles, as this reflects clinical
practice and captures the relevant perspective for the couple. The aim of this
study was to assess the extent to which multiple cycles are reported in MAR
trials. A sample of randomized controlled trials (RCT) was collected on MAR,
published in four time periods, in 11 pre-specified peer-reviewed journals; 253
trials were included: 196 on IVF, 37 on intrauterine insemination and 20 on
ovulation induction. Forty-eight (19%) reported on multiple cycles, which was
significantly more common in trials on intrauterine insemination and ovulation
induction compared with trials on IVF (P < 0.01). Both trials on IVF were multi
centre trials, and those using live birth as primary outcome, reported
significantly more often on multiple cycles (OR 3.7 CI 1.1 to 12.5) and (OR 8.7
CI 1.8 to 40.3), respectively. Trials designed to compare protocol variations
reported multiple cycles less often (OR 0.07 CI 0.01 to 0.74). Most RCT on MAR,
especially those on IVF, do not report cumulative pregnancy rates. As not all
women become pregnant in their first cycle, the clinical significance of these
trials is limited.
PMID- 27616620
TI - Seven out of 10 couples treated by IVF achieve parenthood following either
treatment, natural conception or adoption.
AB - The aim of this study was to explore the achievement of parenthood 8 years after
starting IVF, considering multiple pathways to parenthood during and after IVF
treatment. Medical data on 6507 couples who began IVF between 2000 and 2002 were
obtained from the databases of eight French IVF centres. Information on long-term
outcome was available for participants in the 2008-2010 postal survey. Multiple
imputation methods were used to account for missing data. Eight years after
starting IVF, 71% (95% CI 69 to 74) of treated couples had a child. This included
41% live births after IVF in the IVF centre, 7% live births after another
treatment or after IVF in another centre, 12% live births after spontaneous
conception and 11% adoptions. This study provides a longitudinal overview of
paths to parenthood among couples successfully and unsuccessfully treated by IVF.
These results should give hope to infertile couples as seven out of 10 couples
finally became parents. However, IVF is not the only path to parenthood, and
couples should be informed of the other possible avenues.
PMID- 27616621
TI - Engineering the transposition-based baculovirus expression vector system for
higher efficiency protein production from insect cells.
AB - One of the most common methods for producing recombinant baculovirus for insect
cell protein production involves a transposition mediated system invented over 2
decades ago. This Tn7-mediated system, commercially sold as Bac-to-Bac, has
proven highly useful for construction of high quality baculovirus, but suffers
from a number of drawbacks which reduce the efficiency of the process and limit
its utility for high throughput protein production processes. We describe here
the creation of Bac-2-the-Future, a 2nd generation Tn7-based system for
recombinant baculovirus production which uses optimized expression vectors, new
E. coli strains, and enhanced protocols to dramatically enhance the efficiency of
the baculovirus production process. The new system which we describe eliminates
the need for additional screening of positive clones, improves the efficiency of
transposition, and reduces the cost and time required for high throughput
baculovirus production. The system is compatible with multiple cloning
methodologies, and has been demonstrated to produce baculovirus with equal or
better titer and protein productivity than the currently available systems.
PMID- 27616622
TI - To close or not to close: contemporary indications for patent foramen ovale
closure.
AB - INTRODUCTION: Patent foramen ovale (PFO) is a common congenital cardiac
abnormality and that has been associated with several disease processes including
transient ischemic attacks (TIA), stroke, migraine headaches with aura,
decompression sickness, platypnea-orthodeoxia syndrome, and shunt induced
cyanosis. Controversy exists regarding closure of PFO as a therapeutic treatment
modality for these disease processes. This review addresses the contemporary
clinical indications for PFO closure. Areas covered: We conducted a comprehensive
literature search of contemporary research studies focusing on randomized trials
and meta-analyses comparing medical therapy and device closure of PFOs for the
treatment of PFO associated clinical syndromes. We synthesized this literature
into a review addressing indications for PFO closure in stroke, TIA, migraine
headaches with aura, decompression sickness, platypnea-orthodeoxia syndrome, and
shunt induced cyanosis. Expert commentary: Because in many PFO associated
conditions it can be difficult to determine the degree to which the PFO is a
causative factor in the disease process, we recommend a comprehensive diagnostic
evaluation to exclude other obvious etiologies of PFO associated conditions
before implicating the PFO and proceeding with closure. However in the properly
selected patient population there is growing clinical experience and experimental
evidence suggesting that closure of PFO is a safe and effective treatment
modality.
PMID- 27616623
TI - Who is the real killer? Chlorfenapyr or detergent micelle-chlorfenapyr complex?
AB - 1. Chlorfenapyr [4-bromo-2-(4-chlorophenyl)-1-(ethoxymethl)-5-(trifluoromethyl)
1H-pyrrole-3-carbonitrile] is a commonly employed pesticide throughout the world.
The mechanism of chlorfenapyr action is to uncouple oxidative phosphorylation in
the mitochondria. The characteristic features of chlorfenapyr intoxication are
high fever, rhabdomyolysis and neurologic symptoms that gradually get worse until
death. 2. In recent years, suicide attempt cases using commercial chlorfenapyr
pesticide were reported. Even small doses of commercial chlorfenapyr pesticide
intoxication caused human fatality. However, world health organization (WHO) has
classified chlorfenapyr as class 2-moderately hazardous chemical. Animal studies
using technical grade (94.5%; AC 7504-59A) chlorfenapyr in 0.5% carboxy methyl
cellulose as the vehicle, single dose through oral route in male rats were well
tolerated. 3. We planned a therapeutic strategy for suicidal chlorfenapyr
intoxication, therefore we evaluated the three different toxic doses of
chlorfenapyr (10% chlorfenapyr and 90% detergent) through oral route in male rats
for human extrapolation. The major difference between the technical grade
chlorfenapyr and commercial grade chlorfenapyr was the vehicle. In the technical
grade chlorfenapyr study, 0.5% carboxy methyl cellulose was used as a vehicle,
whereas in the present study 90% detergent acted as a vehicle. The LD50 of
commercial grade chlorfenapyr-40.63 mg/kg bw, which was approximately tenfold
decrease than technical grade chlorfenapyr, LD50 - 441 mg/kg bw. 4. The
combination of chlorfenapyr and detergent, a deadly cocktail to form micelle
complex that can greatly influence bioavailability by attaching to biological
membranes in vivo. To conclude, the enhanced bioavailability of chlorfenapyr by
the detergent causes the fatality in suicidal attempts using chlorfenapyr.
PMID- 27616624
TI - Interleukin 35: A novel candidate biomarker to diagnose early onset sepsis in
neonates.
AB - BACKGROUND: Early onset sepsis (EOS) remains a major cause of morbidity and
mortality in newborns; however, current diagnostic tools are inadequate. We
evaluated the accuracy of a novel cytokine, interleukin (IL)-35, for the
diagnosis of EOS in comparison with other infection markers. METHODS: One hundred
fifty-seven neonates with suspected sepsis in the first 3days of life were
enrolled in this perspective study. All enrolled patients were divided into
infected group and unlikely infected group according to clinical data. IL-35, C
reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and
blood culture were measured once the suspected EOS was documented. RESULTS: Serum
concentration of IL-35 was increased significantly in the infected group compared
with the unlikely infected group (median 36.4 versus 27.1pg/ml, respectively,
p<0.001). The area under receiver-operating characteristic (ROC) curve were 0.756
for IL-35, 0.713 for PCT (age-adjusted), 0.670 for CRP, and 0.619 for WBC. With a
cut-off value of 31.7pg/ml, the diagnostic sensitivity and specificity of IL-35
were 78.48% and 66.67%, respectively. Moreover, unlike PCT concentration, IL-35
concentration did not fluctuate in neonates who were unlikely to be infected
(p=0.885). CONCLUSION: The diagnostic performance of IL-35 was superior to that
of PCT and other commonly used markers, suggesting that IL-35 may be a valuable
tool for EOS diagnosis.
PMID- 27616625
TI - Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease.
AB - BACKGROUND: This study investigated the association of serum B-lymphocyte
activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a
Chinese population. MATERIALS AND METHODS: We enrolled 221 patients with AITD
[170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis
(HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid
autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor
antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and
antithyroglobulin antibody (ATA), were measured at baseline. RESULTS: Serum BAFF
levels were higher in the GD, HT, and AITD groups than in the control group.
Significant correlations were observed between BAFF and TSHRAb levels (r=0.238,
p=0.018), between BAFF and Anti-TPO Ab levels (p=0.038), and between BAFF and ATA
titers (p=0.025) in women but not in men. In addition, serum BAFF levels were
significantly associated with free thyroxine (r=0.430, p=0.004) and TSHRAb
(r=0.495, p=0.001) levels in women with active GD but not in those with inactive
GD. CONCLUSIONS: Serum BAFF levels are increased in GD, HT, and AITD. The
correlation between serum BAFF and TAb levels exhibits a dimorphic pattern,
particularly in active GD.
PMID- 27616626
TI - Enhanced Rho-kinase activity: Pathophysiological relevance in type 2 diabetes.
AB - BACKGROUND: Accumulating evidence indicates that Rho-associated kinase (ROCK) has
been involved in the pathogenesis of insulin resistance and diabetes. However,
little clinical evidence for ROCK activity in diabetic patients is available. We
determined whether ROCK activity is systemically enhanced in type 2 diabetic
patients and associated with other components of diabetes. METHODS: Seventy-eight
volunteers, including 41 type 2 diabetic patients and 37 control subjects, were
participated in this study. Fasting blood samples were collected to measure ROCK
activity in circulating leukocyte, determined by the ratio of
phosphorylation/total myosin-binding subunit (MBS), a direct downstream target of
ROCK. RESULTS: Compared with the control subjects, ROCK activity was
significantly increased in type 2 diabetic patients (phosphorylation/total MBS
ratio 0.80+/-0.10 vs. 0.72+/-0.08, P<0.01). An independent positive correlation
was found between ROCK activity and HbA1c concentration in type 2 diabetic
patients but not in control subjects (r=0.40, P=0.01). In multiple regression
analysis, ROCK activity remains associated significantly in a positive manner
with HbA1c concentration in type 2 diabetes (beta=0.03, P=0.04). CONCLUSIONS:
These findings demonstrated that ROCK activity is significantly increased in type
2 diabetic patients and enhanced ROCK activity may reflect the progression of
disease.
PMID- 27616629
TI - A Fully Integrated and Miniaturized Heavy-metal-detection Sensor Based on Micro
patterned Reduced Graphene Oxide.
AB - For this paper, a fully integrated and highly miniaturized electrochemical sensor
was designed and fabricated on a silicon substrate. A solvothermal-assisted
reduced graphene oxide named "TRGO" was then successfully micro-patterned using a
lithography technique, followed by the electrodeposition of bismuth (Bi) on the
surface of the micro-patterned TRGO for the electrochemical detection of heavy
metal ions. The fully integrated electrochemical micro-sensor was then measured
and evaluated for the detection of cadmium and lead-heavy metal ions in an acetic
acid buffered solution using the square wave anodic stripping voltammetry (SWASV)
technique. The fabricated micro-sensor exhibited a linear detection range of 1.0
MUg L(-1) to 120.0 MUg L(-1) for both of the metal ions, and detection limits of
0.4 MUg L(-1) and 1.0 MUg L(-1) were recorded for the lead and cadmium (S/N = 3),
respectively. Drinking-water samples were used for the practical assessment of
the fabricated micro-sensor, and it showed an acceptable detection performance
regarding the metal ions.
PMID- 27616628
TI - Do individual, online motivational interviewing chat sessions enhance weight loss
in a group-based, online weight control program?
AB - OBJECTIVE: To examine whether the addition of online motivational interviewing
(MI) chats to a Web-based, group behavioral obesity treatment program augments
weight loss outcomes relative to the Web-based weight control program alone.
METHODS: Healthy individuals (N = 398, 24% minority) with overweight/obesity were
randomized to a 36-session group Internet behavioral weight control treatment
(BT) or the same group Internet treatment plus six individual MI chat sessions
(BT + MI). Both conditions received weekly synchronous online chat group sessions
for 6 months followed by 12 monthly group chats. Participants in both groups
received identical behavioral lessons and individualized therapist feedback on
progress toward meeting exercise and calorie goals. BT + MI also received six
individual MI sessions delivered by a separate MI counselor via Web chat. Weight
loss was measured at 6 and 18 months. RESULTS: There were no significant
differences in weight loss between BT (-5.5 +/- 6.0 kg) and BT + MI (-5.1 +/- 6.3
kg) at 6 months or at 18 months (-3.3 +/- 7.1 kg vs. -3.5 +/- 7.7 kg for BT and
BT + MI, respectively). Attendance at group chats did not differ between groups,
nor did self-monitoring patterns, suggesting comparable engagement in the weight
control program in both conditions. CONCLUSIONS: Online MI chat sessions were not
a viable strategy to enhance Web-based weight control treatment outcomes.
PMID- 27616627
TI - Sustained elevation of NF-kappaB activity sensitizes offspring of maternal
inflammation to hypertension via impairing PGC-1alpha recovery.
AB - Growing evidence has demonstrated that maternal detrimental factors, including
inflammation, contribute to the development of hypertension in the offspring. The
current study found that offspring subjected to prenatal exposure of inflammation
by lipopolysaccharide (LPS) challenge during the second semester showed
significantly increased systolic blood pressure. In addition, these offspring
also displayed augmented vascular damage and reactive oxygen species (ROS) levels
in thoracic aortas when challenged with deoxycorticosterone acetate and high-salt
diet (DOCA-salt). Interestingly, the antioxidant N-acetyl-L-cysteine markedly
reversed these changes. Mechanistically, prenatal LPS exposure led to pre
existing elevated peroxisome proliferators-activated receptor-gamma co-activator
(PGC)-1alpha, a critical master of ROS metabolism, which up-regulated the ROS
defense capacity and maintained the balance of ROS generation and elimination
under resting state. However, continued elevation of NF-kappaB activity
significantly suppressed the rapid recovery of PGC-1alpha expression response to
DOCA-salt challenge in offspring that underwent prenatal inflammatory
stimulation. This was further confirmed by using a NF-kappaB inhibitor (N-p-Tosyl
L-phenylalanine chloromethyl ketone) that restored PGC-1alpha recovery and
prevented blood pressure elevation induced by DOCA-salt. Our results suggest that
maternal inflammation programmed proneness to NF-kappaB over-activation which
impaired PGC-1alpha-mediated anti-oxidant capacity resulting in the increased
sensitivity of offspring to hypertensive damage.
PMID- 27616630
TI - Nogo-A does not inhibit retinal axon regeneration in the lizard Gallotia galloti.
AB - The myelin-associated protein Nogo-A contributes to the failure of axon
regeneration in the mammalian central nervous system (CNS). Inhibition of axon
growth by Nogo-A is mediated by the Nogo-66 receptor (NgR). Nonmammalian
vertebrates, however, are capable of spontaneous CNS axon regeneration, and we
have shown that retinal ganglion cell (RGC) axons regenerate in the lizard
Gallotia galloti. Using immunohistochemistry, we observed spatiotemporal
regulation of Nogo-A and NgR in cell bodies and axons of RGCs during ontogeny. In
the adult lizard, expression of Nogo-A was associated with myelinated axon tracts
and upregulated in oligodendrocytes during RGC axon regeneration. NgR became
upregulated in RGCs following optic nerve injury. In in vitro studies, Nogo-A-Fc
failed to inhibit growth of lizard RGC axons. The inhibitor of protein kinase A
(pkA) activity KT5720 blocked growth of lizard RGC axons on substrates of Nogo-A
Fc, but not laminin. On patterned substrates of Nogo-A-Fc, KT5720 caused
restriction of axon growth to areas devoid of Nogo-A-Fc. Levels of cyclic
adenosine monophosphate (cAMP) were elevated over sustained periods in lizard
RGCs following optic nerve lesion. We conclude that Nogo-A and NgR are expressed
in a mammalian-like pattern and are upregulated following optic nerve injury, but
the presence of Nogo-A does not inhibit RGC axon regeneration in the lizard
visual pathway. The results of outgrowth assays suggest that outgrowth-promoting
substrates and activation of the cAMP/pkA signaling pathway play a key role in
spontaneous lizard retinal axon regeneration in the presence of Nogo-A.
Restriction of axon growth by patterned Nogo-A-Fc substrates suggests that Nogo-A
may contribute to axon guidance in the lizard visual system. J. Comp. Neurol.
525:936-954, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616631
TI - Recurrent periductal mastitis: Surgical treatment.
AB - BACKGROUND: Recurrent periductal mastitis is a benign breast disorder that often
features a mammary fistula that runs between periareolar skin and the ductal
mammary system. Due to the high recurrence rate of this disease, its management
is controversial. This study was designed to assess the efficacy of fistulectomy
(Hadfield operation), particularly with regard to its long-term outcome. METHODS:
We reviewed all women with recurrent periductal mastitis who underwent the
Hadfield operation in the Breast Center in S.Orsola-Malpighi Hospital (Bologna
University) from 2005 to 2015. All but one of the patients were heavy smokers and
presented with a recurrent periareolar abscess and a periareolar mammary fistula.
RESULTS: Eighteen women underwent the Hadfield surgical treatment. Mean age at
the time of presentation was 42 years; 17 of 18 women smoked >10 cigarettes/d.
All patients had a breast ultrasonography or mammography. Half of the patients
had undergone antibiotic therapy with one or more prior abscess drainages or
another form of operative treatment. All patients who underwent operative
treatment had no postoperative events and were satisfied with the cosmetic
results. Squamous metaplasia was always present in the specimens. After a median
follow-up of 36 months, 2 patients developed a recurrence after a few months;
neither had stopped smoking. CONCLUSION: Based on our review of the literature
and taking into account the results of this study, it seems clear that the best
treatment involves a combined total excision of the affected duct and the
fistulous tract. Due to the important role of smoking in this disease, it is
important to encourage patients to stop smoking.
PMID- 27616632
TI - Strong light scattering and broadband (UV to IR) photoabsorption in stretchable
3D hybrid architectures based on Aerographite decorated by ZnO nanocrystallites.
AB - In present work, the nano- and microscale tetrapods from zinc oxide were
integrated on the surface of Aerographite material (as backbone) in carbon-metal
oxide hybrid hierarchical network via a simple and single step magnetron
sputtering process. The fabricated hybrid networks are characterized for
morphology, microstructural and optical properties. The cathodoluminescence
investigations revealed interesting luminescence features related to carbon
impurities and inherent host defects in zinc oxide. Because of the wide bandgap
of zinc oxide and its intrinsic defects, the hybrid network absorbs light in the
UV and visible regions, however, this broadband photoabsorption behavior extends
to the infrared (IR) region due to the dependence of the optical properties of
ZnO architectures upon size and shape of constituent nanostructures and their
doping by carbon impurities. Such a phenomenon of broadband photoabsorption
ranging from UV to IR for zinc oxide based hybrid materials is novel.
Additionally, the fabricated network exhibits strong visible light scattering
behavior. The developed Aerographite/nanocrystalline ZnO hybrid network
materials, equipped with broadband photoabsorption and strong light scattering,
are very promising candidates for optoelectronic technologies.
PMID- 27616635
TI - Restaging rectal cancer after neoadjuvant treatment with multiparametric MRI: A
landscape of new opportunities.
PMID- 27616633
TI - Evidence for feasibility of fetal trophoblastic cell-based noninvasive prenatal
testing.
AB - OBJECTIVE: The goal was to develop methods for detection of chromosomal and
subchromosomal abnormalities in fetal cells in the mother's circulation at 10-16
weeks' gestation using analysis by array comparative genomic hybridization (CGH)
and/or next-generation sequencing (NGS). METHOD: Nucleated cells from 30 mL of
blood collected at 10-16 weeks' gestation were separated from red cells by
density fractionation and then immunostained to identify cytokeratin positive and
CD45 negative trophoblasts. Individual cells were picked and subjected to whole
genome amplification, genotyping, and analysis by array CGH and NGS. RESULTS:
Fetal cells were recovered from most samples as documented by Y chromosome PCR,
short tandem repeat analysis, array CGH, and NGS including over 30 normal male
cells, one 47,XXY cell from an affected fetus, one trisomy 18 cell from an
affected fetus, nine cells from a trisomy 21 case, three normal cells and one
trisomy 13 cell from a case with confined placental mosaicism, and two chromosome
15 deletion cells from a case known by CVS to have a 2.7 Mb de novo deletion.
CONCLUSION: We believe that this is the first report of using array CGH and NGS
whole genome sequencing to detect chromosomal abnormalities in fetal
trophoblastic cells from maternal blood. (c) 2016 The Authors. Prenatal Diagnosis
published by John Wiley & Sons, Ltd.
PMID- 27616634
TI - Are patients on basal insulin attaining glycemic targets? Characteristics and
goal achievement of patients with type 2 diabetes mellitus treated with basal
insulin and physician-perceived barriers to achieving glycemic targets.
AB - AIMS: To investigate treatment patterns and achievement of glycemic targets in
patients with type 2 diabetes mellitus treated with basal insulin in a real-world
setting, and to determine physicians' beliefs and practices regarding these
patients. METHODS: This study had two components; a retrospective analysis using
a US claims database of patient and treatment data, and a survey of physicians'
beliefs and practices. RESULTS: A total of 39,074 patients treated with basal
insulin were included in this analysis. The proportion of patients achieving
HbA1c<7.0% (53mmol/mol) was similar in ongoing basal insulin users at baseline
(26%) and at 3months follow-up (27%). The number of new initiators achieving
HbA1c<7.0% (53mmol/mol) increased from baseline (11%) to 3months (27%). In the
physician survey component, the majority of physicians indicated they would
continue to increase basal insulin dose as long as was needed to reach
HbA1c/fasting blood glucose goals (85% of physicians treating 'not on-goal'
patients, 78% of physicians treating 'on-goal' patients). Physician-perceived
barriers to insulin intensification included patient's lifestyle, non-adherence,
and concerns about out-of-pocket costs. CONCLUSIONS: A large proportion of
patients on insulin-based therapy fail to reach glycemic goals. More education of
clinicians may improve insulin intensification rates and increase the proportion
of patients reaching glycemic targets.
PMID- 27616636
TI - Antiplatelet activity of flavonoid and coumarin drugs.
AB - Polyphenols are used as phlebotonic drugs, but their mechanism of action remains
unknown. Since platelet activity and platelet-endothelial cell interactions are
involved in the pathogenesis of cardiovascular disease, this work examines
whether different flavonoid and coumarin drugs are able to inhibit platelet
aggregation. This specific case of coumarins, the antiplatelet effect is not
linked with a possible interaction over blood coagulation since this effect only
dicoumarols have it. The antiplatelet capacity of polyphenols was assayed using
peripheral blood platelets from healthy controls. The distribution of the
different platelets subsets was quantified by flow cytometry, using the calcium
ionophore as a pro-aggregant. The number of GPIIb/IIIa receptors occupied by the
drugs was assayed by flow cytometry using two CD61 surface fluorescein
antibodies. All the polyphenols tested inhibited platelet aggregation. A
percentage antiplatelet activity of 88.91+/-7.98% was recorded for naringin,
48.43+/-8.84% for naringenin, 53.83+/-7.87% for esculetin, 54.65+/-6.91% for
fraxetin, and 25.75+/-4.12% for coumarin. Naringin showed significantly greater
percentage occupation of GPIIb/IIIa receptors than did naringenin (14.82+/-0.81%
vs. 3.90+/-0.55%), and esculetin returned significantly higher values than
fraxetin and coumarin (12.47+/-0.97 vs. 7.53+/-0.49 and 7.90+/-0.69
respectively). All drugs show important antiplatelet activity. Naringin was the
best antiplatelet compound, showing the greatest antiplatelet activity and the
highest percentage binding of GPIIb/IIIa receptors. However, any of the compounds
used could be used in the prevention of cardiovascular disease.
PMID- 27616637
TI - Loss of ASXL1 triggers an apoptotic response in human hematopoietic stem and
progenitor cells.
AB - ASXL1 is frequently mutated in myelodysplastic syndrome and other hematological
malignancies. It has been reported that a loss of ASXL1 leads to a reduction of
H3K27me3 via the polycomb repressive complex 2 (PRC2). To determine the role of
ASXL1 loss in normal hematopoietic stem and progenitor cells, cord blood CD34+
cells were transduced with independent small hairpin interfering RNA lentiviral
vectors against ASXL1 and cultured under myeloid and erythroid permissive
conditions. Knockdown of ASXL1 led to a significant reduction in stem-cell
frequency and a reduced cell expansion along the myeloid lineage. Cell expansion
along the erythroid lineage was also reduced significantly and was accompanied by
an increase in apoptosis of erythroid progenitor cells throughout differentiation
and by an accumulation of cells in the G0/G1 phase. Bone marrow stromal cells
supported the growth of immature erythroid cells, but did not alter the adverse
phenotype of ASXL1 knockdown. Chromatin immunoprecipitation revealed no loss of
H3K27me3 in myeloid progenitor cells, but demonstrated a loss of H3K27me3 on the
HOXA and the p21 locus in erythroid progenitors. We conclude that ASXL1 is
essential for erythroid development and differentiation and that the aberrant
differentiation is, at least in part, facilitated via PRC2.
PMID- 27616638
TI - Sustained enhancement of OCTN1 transporter expression in association with
hydroxyurea induced gamma-globin expression in erythroid progenitors.
AB - The clinical benefits of hydroxyurea (HU) treatment in patients with sickle cell
disease (SCD) are due largely to increased gamma-globin expression. However,
mechanisms that control gamma-globin expression by HU in erythroid progenitors
are incompletely understood. Here, we investigated the role of two HU
transporters, urea transporter B (UTB) and organic cation/carnitine transporter 1
(OCTN1), in this process. Endogenous expression of both transporters peaked
toward the end of erythroid differentiation. However, unlike UTB, HU-induced
OCTN1 expression correlated positively with gamma-globin level and was sustained
throughout the period of induction. These results highlight a potential major
role for OCTN1 in promoting the efficacy of HU.
PMID- 27616639
TI - Identification of phasiRNAs and their drought- responsiveness in Populus
trichocarpa.
AB - Phased, secondary, small interfering RNA (phasiRNA) perform essential biological
functions in plants. However, limited information is available on the role of
phasiRNA genes in Populus (poplar), especially during drought stress. In this
study, we identified 20 PHAS loci generating 91 phasiRNA in the genome of the
model forest tree Populus trichocarpa (P. trichocarpa; western balsam-poplar)
using the control and drought libraries. Our analysis indicated that six PHAS
(PtPHA14-20) initiated by two Populus-specific miRNAs (miR6445 and miR6427) were
specific to Populus. In addition, a total of 47 phasiRNA were found to be drought
responsive, and five of them were confirmed by RT-qPCR. The phase cleavage of
three PHAS loci by miRNA, and degradation of nine transcript targets by phasiRNA
were experimentally confirmed based on degradome data. The identification of
these Populus phasiRNA will contribute to a better understanding of their
function and regulation during drought stress.
PMID- 27616640
TI - Electromyography evaluation of masseter and temporalis, bite force, and quality
of life in elderly patients during the adaptation of mandibular implant-supported
overdentures.
AB - OBJECTIVES: The aim of this study was to investigate the outcomes of the
installation of two implant-supported overdentures until such treatment is
complete. Although this treatment is well established in the literature, there
are no studies comparing what happens to muscles and the quality of life (QoL) of
patients during the treatment. METHODS: We selected 13 completely edentulous
patients, according to inclusion and exclusion criteria, to rehabilitate with
mandibular overdentures retained by two dental implants and a complete denture as
antagonists. We evaluated the efficacy of the treatment and its evolution in five
steps: (i) initially, with the old complete dentures, (ii) after the implants'
placement with the mandibular prosthesis relined, (iii) after the placement of
the healing abutments, (iv) after the installation and adaptation of new
prostheses, and (v) after a 3-month follow-up period. At each stage, we evaluated
patients via temporal and masseter electromyography (EMG), molar and incisive
bite force, and QoL. RESULTS: The results for EMG found a decrease in muscle
activity during rest, the mastication of raisins, and lateral movements when the
overdentures were installed. For the bite force and QoL, there was a gradual
improvement from the placement of the healing abutments period (P ? 0.05), which
was sustained until the follow-up. CONCLUSIONS: Comfort and stability improved
during the treatment, demonstrated by the QoL and bite force results. These
results are positive for elderly patients who might refuse an implant-supported
overdenture due to treatment length.
PMID- 27616642
TI - Ageing changes effective connectivity of motor networks during bimanual finger
coordination.
AB - Bimanual finger coordination declines with age. However, relatively little is
known about the neurophysiological alterations in the motor-system causing this
decline. In the present study, we used 128-channel electroencephalography (EEG)
to evaluate causal interactions of cortical, motor-related brain areas. Right
handed young and elderly subjects performed complex temporally and spatially
coupled as well as temporally coupled and spatially uncoupled finger tappings.
Employing dynamic causal modelling (DCM) for induced responses, we inferred task
induced effective connectivity within a core motor network comprising bilateral
primary motor cortex (M1), lateral premotor cortex (lPM), supplementary motor
area (SMA), and prefrontal cortex (PFC). Behavioural analysis showed
significantly increased error rates and performance times for elderly subjects,
confirming that motor functions decrease with ageing. Additionally, DCM analysis
revealed that this age-related decline can be associated with specific
alterations of interhemispheric and prefrontal to premotor connectivity. Young
and elderly subjects exhibited inhibitory left to right M1-M1 coupling during
performance of temporally and spatially coupled movements. Effects of ageing on
interhemispheric connectivity particularly emerged when movements became
spatially uncoupled. Here, elderly participants still expressed inhibitory left
to right M1-M1 coupling, whereas no such connection was present in the young.
Furthermore, ageing affected prefrontal to premotor connectivity. In all
conditions, elderly subjects showed significant couplings from left PFC to left
lPM. In contrast, young participants exhibited left PFC to SMA connections. These
results demonstrate that (i) in spatially uncoupled movements interhemispheric M1
connectivity increases with age and (ii) support the idea that ageing is
associated with enhanced lateral prefrontal to premotor coupling (PFC to lPM) and
hypoactivation of a medial pathway (PFC to SMA) within the dominant hemisphere.
PMID- 27616643
TI - Mussel-inspired approach to constructing robust cobalt-embedded N-doped carbon
nanosheet toward enhanced sulphate radical-based oxidation.
AB - Heterogeneous sulphate radical based advanced oxidation processes (SR-AOPs) have
lately been raised as a promising candidate for water treatment. Despite the
progress made, either the stability or the performance of the current catalysts
is still far from satisfactory for practical applications. Herein, using
polydopamine-cobalt ion complex that inspired by mussel proteins as medium, we
facilely fabricate a robust SR-AOPs catalyst with cobalt nanoparticles (NPs)
embedded in nitrogen-doped reduced graphene oxide matrix (NRGO@Co). The NRGO
scaffold with high porosity and surface area not only stabilizes the NPs but also
greatly facilitates the accessibility and adsorption of substrates to the active
sites. With the synergistic effect arising from the NRGO and Co NPs, the NRGO@Co
hybrid catalyst exhibits enhanced catalytic activity for activation of
peroxymonosulfate (PMS) to degrade organic pollutants in water. Furthermore,
taking advantage of the favorable magnetic properties, the catalyst can be easily
recycled and reused for at least 4 runs with negligible loss of activity. Coupled
with systematic investigation in terms of influential factors, mineralization,
and radicals identification, make the catalyst hold significant potential for
application in remediation of organic pollutants in water.
PMID- 27616641
TI - Functional magnetic resonance imaging of the cervical spinal cord during thermal
stimulation across consecutive runs.
AB - The spinal cord is the first site of nociceptive processing in the central
nervous system and has a role in the development and perpetuation of clinical
pain states. Advancements in functional magnetic resonance imaging are providing
a means to non-invasively measure spinal cord function, and functional magnetic
resonance imaging may provide an objective method to study spinal cord
nociceptive processing in humans. In this study, we tested the validity and
reliability of functional magnetic resonance imaging using a selective field-of
view gradient-echo echo-planar-imaging sequence to detect activity induced blood
oxygenation level-dependent signal changes in the cervical spinal cord of healthy
volunteers during warm and painful thermal stimulation across consecutive runs.
At the group and subject level, the activity was localized more to the dorsal
hemicord, the spatial extent and magnitude of the activity was greater for the
painful stimulus than the warm stimulus, and the spatial extent and magnitude of
the activity exceeded that of a control analysis. Furthermore, the spatial extent
of the activity for the painful stimuli increased across the runs likely
reflecting sensitization. Overall, the spatial localization of the activity
varied considerably across the runs, but despite this variability, a machine
learning algorithm was able to successfully decode the stimuli in the spinal cord
based on the distributed pattern of the activity. In conclusion, we were able to
successfully detect and characterize cervical spinal cord activity during thermal
stimulation at the group and subject level.
PMID- 27616644
TI - Elevation of serum dipeptidyl peptidase-4 activity in type 1 diabetes: Potential
explanations and implications.
PMID- 27616645
TI - In vivo quantification of the secretion rates of the hemolysin A Type I secretion
system.
AB - Type 1 secretion systems (T1SS) of Gram-negative bacteria secrete a broad range
of substrates into the extracellular space. Common to all substrates is a C
terminal secretion sequence and nonapeptide repeats in the C-terminal part that
bind Ca(2+) in the extracellular space, to trigger protein folding. Like all
T1SS, the hemolysin A (HlyA) T1SS of Escherichia coli consists of an ABC
transporter, a membrane fusion protein and an outer membrane protein allowing the
one step translocation of the substrate across both membranes. Here, we analyzed
the secretion rate of the HlyA T1SS. Our results demonstrate that the rate is
independent of substrate-size and operates at a speed of approximately 16 amino
acids per transporter per second. We also demonstrate that the rate is
independent of the extracellular Ca(2+) concentration raising the question of the
driving force of substrate secretion by T1SS in general.
PMID- 27616646
TI - Bayesian Maximum Entropy space/time estimation of surface water chloride in
Maryland using river distances.
AB - Widespread contamination of surface water chloride is an emerging environmental
concern. Consequently accurate and cost-effective methods are needed to estimate
chloride along all river miles of potentially contaminated watersheds. Here we
introduce a Bayesian Maximum Entropy (BME) space/time geostatistical estimation
framework that uses river distances, and we compare it with Euclidean BME to
estimate surface water chloride from 2005 to 2014 in the Gunpowder-Patapsco,
Severn, and Patuxent subbasins in Maryland. River BME improves the cross
validation R2 by 23.67% over Euclidean BME, and river BME maps are significantly
different than Euclidean BME maps, indicating that it is important to use river
BME maps to assess water quality impairment. The river BME maps of chloride
concentration show wide contamination throughout Baltimore and Columbia-Ellicott
cities, the disappearance of a clean buffer separating these two large urban
areas, and the emergence of multiple localized pockets of contamination in
surrounding areas. The number of impaired river miles increased by 0.55% per year
in 2005-2009 and by 1.23% per year in 2011-2014, corresponding to a marked
acceleration of the rate of impairment. Our results support the need for control
measures and increased monitoring of unassessed river miles.
PMID- 27616647
TI - Reproductive toxicity of azoxystrobin to adult zebrafish (Danio rerio).
AB - In the past few decades, extensive application of azoxystrobin has led to great
concern regarding its adverse effects on aquatic organisms. The objective of the
present study was to evaluate the reproductive toxicity of azoxystrobin to
zebrafish. After adult zebrafish of both sexes were exposed to 2, 20 and 200
MUg/L azoxystrobin for 21 days, egg production, the fertilization rate, the
gonadosomatic index (GSI) and hepatosomatic index (HSI), 17beta-estradiol (E2),
testosterone (T) and vitellogenin (Vtg) concentrations, and histological
alterations in the gonads and livers were measured. Meanwhile, expression
alterations of genes encoding gonadotropins and gonadotropin receptors (fshb,
lhb, fshr and lhr), steroid hormone receptors (era, er2b and ar), steroidogenic
enzymes (cyp11a, cyp11b, cyp17, cyp19a, cyp19b, hsd3b and hsd17b) in the
hypothalamic-pituitary-gonad (HPG) axis and vitellogenin (vtg1 and vtg2) in the
livers were also investigated. The results showed that reduced egg production and
fertilization rates were observed at 200 MUg/L azoxystrobin. In female zebrafish,
reduced E2 and Vtg concentrations, decreased GSI, increased T concentrations, and
histological alterations in the ovaries and livers were observed at 200 MUg/L
azoxystrobin, along with significant down-regulation of lhb, cyp19b, lhr, cyp19a,
vtg1 and vtg2, and up-regulation of cyp17, hsd3b and hsd17b. In male zebrafish,
increased E2 and Vtg concentrations, reduced T concentration and GSI, and
histological alterations in the testes and livers were observed after exposure to
20 and 200 MUg/L azoxystrobin, along with significant up-regulations of cyp19b,
cyp11a, cyp17, cyp19a, hsd3b and hsd17b, vtg1 and vtg2. Moreover, cyp11a, hsd3b,
cyp19a, vtg1 and vtg2 in male zebrafish were significantly up-regulated after
treatment with 2 MUg/L azoxystrobin. The results of the present study indicate
that azoxystrobin led to reproductive toxicity in zebrafish and male zebrafish
were more sensitive to azoxystrobin than female zebrafish.
PMID- 27616648
TI - Relative developmental toxicity of short-chain chlorinated paraffins in Zebrafish
(Danio rerio) embryos.
AB - Short-chain chlorinated paraffins (SCCPs) are ubiquitous in the environment and
might cause adverse environmental and human health effects. Little is known about
the relative toxicity of different SCCP compounds especially during development.
The objective of this study was to characterize and compare effects of seven SCCP
groups at environmentally relevant levels, using a zebrafish (Danio rerio) model.
Observations on malformation, survival rates at 96 h post fertilization (hpf),
and hatching rates at 72 hpf indicated that the C10- groups (C10H18Cl4,
1,2,5,6,9,10-C10H16Cl6 and C10H15Cl7) were more toxic than the C12- groups
(C12H22Cl4, C12H19Cl7 and 1,1,1,3,10,12,12,12-C12H18Cl8) and Cereclor 63L. The
C10- groups were also more potent than C12- groups and Cereclor 63L in decreasing
thyroid hormone levels. Among the three compounds within the C10- group, the
compounds with less chlorine content had stronger effects on sub-lethal
malformations but less effects on triiodothyronine (T3) and tetraiodothyronine
(T4). Only C10H18Cl4 significantly decreased the mRNA expression of tyr, ttr,
dio2 and dio3 at a dose-dependent manner suggesting that the specific mode of
actions differ with different congeners. The mechanisms of disruption of thyroid
status by different SCCPs could be different. C10H18Cl4 might inhibit T3
production through the inhibition effect on dio2. These results indicate that
SCCP exposure could alter gene expression in the hypothalamic-pituitary-thyroid
(HPT) axis and thyroid hormone levels. The mechanisms of disruption of thyroid
status by different SCCPs could be different. Our results on the relative
developmental toxicities of SCCPs will be useful to reach a better understanding
of SCCP toxicity supporting environmental risk evaluation and regulation and used
as a guidance for environmental monitoring of SCCPs in the future.
PMID- 27616649
TI - Quantification of long-term primary and secondary source contributions to
carbonaceous aerosols.
AB - Ambient fine particulate matter samples were collected during 2009-2013 in
Chengdu, a megacity in western China, and the samples were speciated into organic
carbon (OC), elemental carbon (EC), char-EC, soot-EC, eight carbon fractions,
inorganic elements and water-soluble ions. Char-EC and soot-EC contribute to the
better understanding of the sources and properties of EC. The highest levels of
most carbon fractions were found in winter and May. The higher OC/EC ratio in
winter suggests higher SOC fraction in winter, and higher char-EC/soot-EC ratio
in May are the direct consequences of straw burning activities. Source
contributions to PM2.5 and carbonaceous aerosols were quantified using the ME2
receptor model. Major contributors to OC in PM2.5 are vehicular exhaust (36.5%),
coal combustion & straw burning (35.2%) and SOC (27.0%). The first two categories
also contributed 51.4% and 49.3% of char-EC in PM2.5. Vehicular exhaust dominated
soot-EC, contributing 63.0% to soot-EC in PM2.5. SOC contributed to high OC
levels in winter due to the increase of precursor emissions and stable
meteorological conditions. Coal combustion & straw burning show higher
contributions to OC, char-EC and soot-EC in winter months and in May, which can
be explained, in part, by increased coal consumption in winter and straw burning
activities in May. Vehicular exhaust contributions are not strongly associated
with monthly nor weekday-weekend patterns, resulting in that soot-EC vary
insignificantly by month nor by weekday.
PMID- 27616650
TI - Microplastic pollution in the Greenland Sea: Background levels and selective
contamination of planktivorous diving seabirds.
AB - Microplastics have been reported everywhere around the globe. With very limited
human activities, the Arctic is distant from major sources of microplastics.
However, microplastic ingestions have been found in several Arctic marine
predators, confirming their presence in this region. Nonetheless, existing
information for this area remains scarce, thus there is an urgent need to
quantify the contamination of Arctic marine waters. In this context, we studied
microplastic abundance and composition within the zooplankton community off East
Greenland. For the same area, we concurrently evaluated microplastic
contamination of little auks (Alle alle), an Arctic seabird feeding on
zooplankton while diving between 0 and 50 m. The study took place off East
Greenland in July 2005 and 2014, under strongly contrasted sea-ice conditions.
Among all samples, 97.2% of the debris found were filaments. Despite the
remoteness of our study area, microplastic abundances were comparable to those of
other oceans, with 0.99 +/- 0.62 m-3 in the presence of sea-ice (2005), and 2.38
+/- 1.11 m-3 in the nearby absence of sea-ice (2014). Microplastic rise between
2005 and 2014 might be linked to an increase in plastic production worldwide or
to lower sea-ice extents in 2014, as sea-ice can represent a sink for
microplastic particles, which are subsequently released to the water column upon
melting. Crucially, all birds had eaten plastic filaments, and they collected
high levels of microplastics compared to background levels with 9.99 and 8.99
pieces per chick meal in 2005 and 2014, respectively. Importantly, we also
demonstrated that little auks took more often light colored microplastics, rather
than darker ones, strongly suggesting an active contamination with birds
mistaking microplastics for their natural prey. Overall, our study stresses the
great vulnerability of Arctic marine species to microplastic pollution in a
warming Arctic, where sea-ice melting is expected to release vast volumes of
trapped debris.
PMID- 27616651
TI - Physico-chemical and biological characterization of urban municipal landfill
leachate.
AB - Unscientific management and ad-hoc approaches in municipal solid waste management
have led to a generation of voluminous leachate in urban conglomerates.
Quantification, quality assessment, following treatment and management of
leachate has become a serious problem worldwide. In this context, the present
study investigates the physico-chemical and biological characterization of
landfill leachate and nearby water sources and attempts to identify relationships
between the key parameters together with understanding the various processes for
chemical transformations. The analysis shows an intermediate leachate age (5-10
years) with higher nutrient levels of 10,000-12,000 mg/l and ~2000-3000 mg/l of
carbon (COD) and nitrogen (TKN) respectively. Elemental analysis and underlying
mechanisms reveal chemical precipitation and co-precipitation as the vital
processes in leachate pond systems resulting in accumulation of trace metals.
Based on the above criteria the samples were clustered into major groups that
showed a clear distinction between leachate and water bodies. The microbial
analysis showed bacterial communities correlating with specific factors relevant
to redox environments indicating a gradient in nature and abundance of biotic
diversity with a change in leachate environment. Finally, the quality and the
contamination potential of the samples were evaluated with the help of leachate
pollution index (LPI) and water quality index (WQI) analysis. The study helps in
understanding the contamination potential of landfill leachate and establishes
linkages between microbial communities and physico-chemical parameters for
effective management of landfill leachate.
PMID- 27616652
TI - The association between muscle strengthening activities and atherogenic index of
plasma.
AB - Atherogenic index of plasma (AIP), calculated as LOG10(triglycerides/high-density
lipoprotein-cholesterol), is considered to be a novel indicator of cardiovascular
disease (CVD) risk. Muscle strengthening activities (MSA) have been shown to
favorably associate with triglycerides and high-density lipoprotein cholesterol
(HDL-C). The association between MSA and AIP has yet to be explored in a
nationally representative sample of U.S. adults, which was the purpose of this
brief report. Data from the 1999-2006 National Health and Nutrition Examination
Survey were used (N=6694 adults 20-85yrs). AIP was obtained from a blood sample
and a 2-item questionnaire was implemented to assess MSA participation over the
previous 30-days. Individuals meeting MSA guidelines (vs. not) had reduced odds
of having an elevated (>0.24) AIP (odds ratio=0.80; 95% confidence interval: 0.65
0.98; P=0.03). Muscle strengthening activities appear to be inversely associated
with AIP. Engaging in MSA may be a strategy to mitigate risk for health outcomes
associated with an elevated AIP, such as CVD.
PMID- 27616654
TI - An exploratory investigation of sexual health screening in the first 12 weeks of
case management in populations with severe mental illness.
AB - The sexual health of people with mental illness is commonly overlooked, neglected
or inadequately addressed in mental health care, despite evidence showing that
people with severe mental illness are more vulnerable to sexually transmitted
infections (including HIV), sexual side-effects, and sexual dysfunction than the
general population. This article reports a study that investigated sexual health
screening in five community mental health clinics within a large a regional
health service in Victoria, Australia. The aim of the study was to examine the
extent to which sexual health screening is currently undertaken on newly admitted
case-managed consumers, and to identify the types of screening undertaken. An
exploratory design using retrospective file audit was used in the study. A total
of 186 medical records met the study inclusion criteria. The study found that
less than 40% of consumers were provided with sexual health screening during
their first 12 weeks of case management. The study also found that sexual side
effects, issues of fertility, sexual self-esteem, safe sexual practices, and
sexual dysfunction were rarely screened for. Poor sexual health screening has
implications for the safety and quality of mental health care and requires
targeted research to improve understandings and approaches to care.
PMID- 27616653
TI - Analysis of single nucleotide polymorphisms based on RNA sequencing data of
diverse bio-geographical accessions in barley.
AB - Barley is one of the founder crops of Old world agriculture and has become the
fourth most important cereal worldwide. Information on genome-scale DNA
polymorphisms allows elucidating the evolutionary history behind domestication,
as well as discovering and isolating useful genes for molecular breeding. Deep
transcriptome sequencing enables the exploration of sequence variations in
transcribed sequences; such analysis is particularly useful for species with
large and complex genomes, such as barley. In this study, we performed RNA
sequencing of 20 barley accessions, comprising representatives of several
biogeographic regions and a wild ancestor. We identified 38,729 to 79,949 SNPs in
the 19 domesticated accessions and 55,403 SNPs in the wild barley and revealed
their genome-wide distribution using a reference genome. Genome-scale comparisons
among accessions showed a clear differentiation between oriental and occidental
barley populations. The results based on population structure analyses provide
genome-scale properties of sub-populations grouped to oriental, occidental and
marginal groups in barley. Our findings suggest that the oriental population of
domesticated barley has genomic variations distinct from those in occidental
groups, which might have contributed to barley's domestication.
PMID- 27616655
TI - Risk factors for bacteremia and central line-associated blood stream infections
in children with acute myelogenous leukemia: A single-institution report.
AB - BACKGROUND: Central line-associated blood stream infections (CLABSIs) are a
source of high morbidity and mortality in children with acute myelogenous
leukemia (AML). PROCEDURE: To understand the epidemiology and risk factors
associated with the development of CLABSI in children with AML. METHODS: We
retrospectively reviewed all patients with AML over a 5-year period between 2007
and 2011 at the Children's Hospital Colorado. Cases and controls were classified
on the basis of the presence of a CLABSI as defined by the National Healthcare
Safety Network. RESULTS: Of 40 patients in the study, 25 (62.5%) developed at
least one CLABSI during therapy. The majority of CLABSIs were due to oral or
gastrointestinal organisms (83.0%). Skin organisms accounted for 8.5%. In a
multivariable analysis, the strongest risk factors associated with CLABSI were
diarrhea (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6-28.7), receipt of
blood products in the preceding 4-7 days (OR 10.0, 95%CI 3.2-31.0), not receiving
antibiotics (OR 8.3, 95%CI 2.8-25.0), and chemotherapy cycle (OR 3.5, 95%CI 1.4
8.9). CLABSIs led to increased morbidity, with 13 cases (32.5%) versus two
controls (1.9%) requiring transfer to the pediatric intensive care unit (P <
0.001). Three (7.5%) of 40 CLABSI events resulted in or contributed to death.
CONCLUSIONS: Intensified line care efforts cannot eliminate all CLABSIs in the
patients with AML. Exploring the role of mucosal barrier breakdown and/or the use
of antibiotic prophylaxis may be effective strategies for further prevention of
CLABSIs, supporting ongoing trials in this patient population.
PMID- 27616657
TI - Signal attenuation of PFG restricted anomalous diffusions in plate, sphere, and
cylinder.
AB - Pulsed field gradient (PFG) NMR is a noninvasive tool to study anomalous
diffusion, which exists widely in many systems such as in polymer or biological
systems, in porous material, in single file structures and in fractal geometries.
In a real system, the diffusion could be a restricted or a tortuous anomalous
diffusion, rather than a free diffusion as the domains for fast and slow
transport could coexist. Though there are signal attenuation expressions for free
anomalous diffusion in literature, the signal attenuation formalisms for
restricted anomalous diffusion is very limited, except for a restricted time
fractional diffusion within a plate reported recently. To better understand the
PFG restricted fractional diffusion, in this paper, the PFG signal attenuation
expressions were derived for three typical structures (plate, sphere, and
cylinder) based on two models: fractal derivative model and fractional derivative
model. These signal attenuation expressions include two parts, the time part
Tn(t) and the space part Xn(r). Unlike normal diffusion, the time part Tn(t) in
time-fractional diffusion can be either a Mittag-Leffler function from the
fractional derivative model or a stretched exponential function from the fractal
derivative model. However, provided the restricted normal diffusion and the
restricted time-fractional diffusion are in an identical structure, they will
have the same space part Xn(r) as both diffusions have the same space derivative
parameter beta equaling 2, therefore, they should have similar diffractive
patterns. The restricted general fractional diffusion within a plate is also
investigated, which indicates that at a long time limit, the diffusion type is
insignificant to the diffractive pattern that depends only on the structure and
the gradient pulses. The expressions describing the time-dependent behaviors of
apparent diffusion coefficient Df,app for restricted anomalous diffusion are also
proposed in this paper. Both the short and long time-dependent behaviors of
Df,app are distinct from that of normal diffusion. The general expressions for
PFG restricted curvilinear diffusion of tube model were derived in a conventional
way and its result agree with that obtained from the fractional derivative model
with alpha equaling 1/2. Additionally, continuous-time random walk simulation was
performed to give good support to the theoretical results. These theoretical
results reported here will be valuable for researchers in analyzing PFG anomalous
diffusion.
PMID- 27616656
TI - Caspase Inhibition Prevents Tumor Necrosis Factor-alpha-Induced Apoptosis and
Promotes Necrotic Cell Death in Mouse Hepatocytes in Vivo and in Vitro.
AB - How different cell death modes and cell survival pathways cross talk remains
elusive. We determined the interrelation of apoptosis, necrosis, and autophagy in
tumor necrosis factor (TNF)-alpha/actinomycin D (ActD) and lipopolysaccharide/D
galactosamine (GalN)-induced hepatotoxicity in vitro and in vivo. We found that
TNF-alpha/ActD-induced apoptosis was completely blocked by a general caspase
inhibitor ZVAD-fmk at 24 hours but hepatocytes still died by necrosis at 48
hours. Inhibition of caspases also protected mice against lipopolysaccharide/GalN
induced apoptosis and liver injury at the early time point, but this protection
was diminished after prolonged treatment by switching apoptosis to necrosis.
Inhibition of receptor-interacting protein kinase (RIP)1 by necrostatin 1
partially inhibited TNF-alpha/ZVAD-induced necrosis in primary hepatocytes.
Pharmacologic inhibition of autophagy or genetic deletion of Atg5 in hepatocytes
did not protect against TNF-alpha/ActD/ZVAD-induced necrosis. Moreover,
pharmacologic inhibition of RIP1 or genetic deletion of RIP3 failed to protect
and even exacerbated liver injury after mice were treated with
lipopolysaccharide/GalN and a pan-caspase inhibitor. In conclusion, our results
suggest that different cell death mode and cell survival pathways are closely
integrated during TNF-alpha-induced liver injury when both caspases and NF-kappaB
are blocked. Moreover, results from our study also raised concerns about the
safety of currently ongoing clinical trials that use caspase inhibitors.
PMID- 27616658
TI - The significance of the increased expression of phosphorylated MeCP2 in the
membranes from patients with proliferative diabetic retinopathy.
AB - The purpose of this study was to evaluate the correlation of expression of
phosphorylated methyl-CpG binding protein 2-Ser421 (MeCP2-S421) and VEGF in the
membranes of patients with PDR. We examined the expression of phospho-MeCP2-S80,
S421, VEGF and PEDF in surgically excised PDR membranes from 33 patients with
diabetes, and idiopathic epiretinal membranes from 11 patients without diabetes,
using immunohistochemistry and western blot. The colocalization of MeCP2-S421
with VEGF, PEDF, CD31, GFAP and alphaSMA was revealed by fluorescent double
labeling. The effect of CoCl2 and knock down MeCP2 using specific siRNA on the
expression of MeCP2 and VEGF were analyzed in HUCAC cells by Western blot. We
found that phospho-MeCP2-S421 was significantly increased in the membranes from
the patients with PDR compared with the specimens from patients without diabetes
(P < 0.01). The expression of phospho-MeCP2-S421 was much stronger than that of
phospho-MeCP2-S80 in the PDR membranes. Double labeling showed that the high
phospho-MeCP2-S421 expression was associated with strong expression of VEGF, but
not PEDF. Further, phospho-MeCP2-S421 and VEGF were increased by the stimulation
of CoCl2 and knock down MeCP2 inhibited the expression of VEGF. Our result
suggests that phospho-MeCP2-S421 might involve in the pathogenesis of PDR.
PMID- 27616660
TI - Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle
penetration.
AB - Nanoparticle penetration through tumor tissue after extravasation is considered
as a key issue for tumor distribution and therapeutic effects. Most tumors
possess abundant stroma, a fibrotic tissue composed of cancer-associated
fibroblasts (CAFs) and extracellular matrix (ECM), which acts as a barrier for
nanoparticle penetration. There is however a lack of suitable in vitro systems to
study the tumor stroma penetration of nanoparticles. In the present study, we
developed and thoroughly characterized a 3D co-culture spheroidal array to mimic
tumor stroma and investigated the penetration of silica and PLGA nanoparticles in
these spheroids. First, we examined human breast tumor patient biopsies to
characterize the content and organization of stroma and found a high expression
of alpha-smooth muscle actin (alpha-SMA; 40% positive area) and collagen-1 (50%
positive area). Next, we prepared homospheroids of 4T1 mouse breast cancer cells
or 3T3 mouse fibroblasts alone as well as heterospheroids combining 3T3 and 4T1
cells in different ratios (1:1 and 5:1) using a microwell array platform.
Confocal live imaging revealed that fibroblasts distributed and reorganized
within 48h in heterospheroids. Furthermore, immunohistochemical staining and gene
expression analysis showed a proportional increase of alpha-SMA and collagen in
heterospheroids with higher fibroblast ratios attaining 35% and 45% positive area
at 5:1 (3T3:4T1) ratio, in a good match with the clinical breast tumor stroma.
Subsequently, we studied the penetration of high and low negatively charged
fluorescent silica nanoparticles (30nm; red and 100 or 70nm; green; zeta
potential: -40mV and -20mV) and as well as Cy5-conjugated pegylated PLGA
nanoparticles (200nm, -7mV) in both homo- and heterospheroid models. Fluorescent
microscopy on spheroid cryosections after incubation with silica nanoparticles
showed that 4T1 homospheroids allowed a high penetration of about 75-80% within
24h, with higher penetration in case of the 30nm nanoparticles. In contrast,
spheroids with increasing fibroblast amounts significantly inhibited NP
penetration. Silica nanoparticles with a less negative zeta potential exhibited
lesser penetration compared to highly negative charged nanoparticles.
Subsequently, similar experiments were conducted using Cy5-conjugated pegylated
PLGA nanoparticles and confocal laser scanning microscopy; an increased
nanoparticle penetration was found in 4T1 homospheroids until 48h, but
significantly lower penetration in heterospheroids. Furthermore, we also
developed human homospheroids (MDA-MB-231 or Panc-1 tumor cells) and
heterospheroids (MDA-MB-231/BJ-hTert and Panc-1/pancreatic stellate cells) and
performed silica nanoparticle (30 and 100nm) penetration studies. As a result,
heterospheroids had significantly a lesser penetration of the nanoparticles
compared to homospheroids. In conclusion, our data demonstrate that tumor stroma
acts as a strong barrier for nanoparticle penetration. The 30-nm nanoparticles
with low zeta potential favor deeper penetration. Furthermore, the herein
proposed 3D co-culture platform that mimics the tumor stroma, is ideally suited
to systematically investigate the factors influencing the penetration
characteristics of newly developed nanomedicines to allow the design of
nanoparticles with optimal penetration characteristics.
PMID- 27616661
TI - Epidemiology of Barrett's esophagus and esophageal adenocarcinoma in Spain. A
unicentric study.
AB - INTRODUCTION: Barrett's esophagus (BE) is an acquired disease defined by the
presence of intestinal metaplasia with goblet cells in the distal esophagus. The
prevalence of BE has increased dramatically over the last years. AIMS: The
primary aims of the study were to analyze the characteristics of BE and
esophageal adenocarcinoma (EAC) in a Spanish health district during a follow-up
period. METHODOLOGY: Sociodemographic factors, alcohol consumption and cigarette
smoking were analyzed. We also studied the histological behavior and cause of
death in each group. RESULTS: In the present study 430 patients were included,
338 with BE and 92 with EAC. Incidence rates have risen from 2.25 and 1.25 per
100,000 inhabitants in 1996 to 6.5 and 4.75 per 100,000 in 2011, respectively. In
the EAC group, male gender, age and alcohol consumption were higher in comparison
to the BE group, and the overall survival was 23 months. In the BE group, the
main causes of death were non-esophageal cancer and cardiovascular disease.
CONCLUSIONS: The incidence and prevalence rates of AEC and BE have risen over the
past years. Risk factors for these conditions were male gender, age and alcohol
consumption. Long BE (> 3 cm) is involved in dysplasia progression. AEC diagnosis
mainly occurs after neoplasia is detected and, in a few cases, due to a previous
BE. Cardiovascular diseases and non-esophageal cancers have been found to be the
main cause of death in BE patients.
PMID- 27616659
TI - Involvement of mitochondrial permeability transition pore (mPTP) in cardiac
arrhythmias: Evidence from cyclophilin D knockout mice.
AB - In the present study, we have used a genetic mouse model that lacks cyclophilin D
(CypD KO) to assess the cardioprotective effect of mitochondrial permeability
transition pore (mPTP) inhibition on Ca2+ waves and Ca2+ alternans at the single
cell level, and cardiac arrhythmias in whole-heart preparations. The protonophore
carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) caused mitochondrial
membrane potential depolarization to the same extent in cardiomyocytes from both
WT and CypD KO mice, however, cardiomyocytes from CypD KO mice exhibited
significantly less mPTP opening than cardiomyocytes from WT mice (p<0.05).
Consistent with these results, FCCP caused significant increases in CaW rate in
WT cardiomyocytes (p<0.05) but not in CypD KO cardiomyocytes. Furthermore, the
incidence of Ca2+ alternans after treatment with FCCP and programmed stimulation
was significantly higher in WT cardiomyocytes (11 of 13), than in WT
cardiomyocytes treated with CsA (2 of 8; p<0.05) or CypD KO cardiomyocytes (2 of
10; p<0.01). (Pseudo-)Lead II ECGs were recorded from ex vivo hearts. We observed
ST-T-wave alternans (a precursor of lethal arrhythmias) in 5 of 7 WT hearts. ST-T
wave alternans was not seen in CypD KO hearts (n=5) and in only 1 of 6 WT hearts
treated with CsA. Consistent with these results, WT hearts exhibited a
significantly higher average arrhythmia score than CypD KO (p<0.01) hearts
subjected to FCCP treatment or chemical ischemia-reperfusion (p<0.01). In
conclusion, CypD deficiency- induced mPTP inhibition attenuates CaWs and Ca2+
alternans during mitochondrial depolarization, and thereby protects against
arrhythmogenesis in the heart.
PMID- 27616662
TI - Concerns about environmental mercury toxicity: do we forget something else?
PMID- 27616664
TI - The role of weather and density dependence on population dynamics of Alpine
dwelling red deer.
AB - The dynamics of red deer Cervus elaphus populations has been investigated across
different environmental conditions, with the notable exception of the European
Alps. Although the population dynamics of mountain-dwelling ungulates is
typically influenced by the interaction between winter severity and density, the
increase of temperatures and the reduction of snowpack occurring on the Alps
since the 1980s may be expected to alter this pattern, especially in populations
dwelling at medium - low elevations. Taking advantage of a 29-year time series of
spring count data, we explored the role of weather stochasticity and density
dependence on growth rate and vital rates (mortality and weaning success), and
the density-dependent variation in body mass in a red deer population of the
Italian Alps. The interaction between increasing values of density and snow depth
exerted negative and positive effects on growth and mortality rates,
respectively, while weaning success was negatively affected by increasing values
of density, female-biased sex ratio and snow depth. Body mass of males and
females of different age classes declined as population size increased. Our data
support the role of winter severity and density dependence as key components of
red deer population dynamics, and provide insight into the species' ecology on
the European Alps. Despite the recent decline of snowpack on the Alpine Region,
the negative impacts of winter severity and population abundance on growth rrate
(possibly mediated by the density-dependent decline in body mass) confirms the
importance of overwinter mortality in affecting the population dynamics of Alpine
dwelling red deer.
PMID- 27616663
TI - Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic
polymorphism.
AB - The aim of the present study was to evaluate the association between prenatal
exposure to mercury (Hg) and neurodevelopment of the child, taking into account
genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders.
Six hundred and one mother-child pairs were recruited from the central Slovenia
region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The
total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third
Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was
performed on 361 children; 237 of them were from Slovenia and 124 from Croatia.
The results showed negative association between low-to-moderate Hg exposure in
children with normal neurodevelopmental outcome and cognitive and fine motor
scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in
cognitive score was observed only in children carrying at least one Apoe epsilon4
allele, while the decrease in fine motor scores was independent of the Apoe
genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive
association between Se and the language score and a negative association between
Pb and the motor score was observed, but not in the subgroup of children carrying
the epsilon4 allele.
PMID- 27616665
TI - Media Use and Exposure to Graphic Content in the Week Following the Boston
Marathon Bombings.
AB - Traditional and new media inform and expose the public to potentially distressing
graphic content following disasters, but predictors of media use have received
limited attention. We examine media-use patterns after the Boston Marathon
bombings (BMB) in a representative national U.S. sample (n = 2888), with
representative oversamples from metropolitan Boston (n = 845) and New York City
(n = 941). Respondents completed an Internet-based survey 2-4 weeks post-BMB. Use
of traditional media was correlated with older age, prior indirect media-based
exposure to collective traumas, and direct BMB exposure. New media use was
correlated with younger age and prior direct exposure to collective traumas.
Increased television and online news viewing were associated with exposure to
more graphic content. The relationship between traditional and new media was
stronger for young adults than all other age groups. We offer insights about the
relationship between prior collective trauma exposures and media use following
subsequent disasters and identify media sources likely to expose people to
graphic content.
PMID- 27616666
TI - Gene expression study of phase I and II metabolizing enzymes in RPTEC/TERT1 cell
line: application in in vitro nephrotoxicity prediction.
AB - 1. The phase I and II metabolizing enzymes of kidneys play an important role in
the metabolism of xenobiotic as well as endogenous compounds and proximal tubules
of kidney constitute high concentration of these metabolizing enzymes compared
with the other parts. 2. It has been shown previously that differential enzyme
expression among human and rodent/non-rodent species can be a roadblock in drug
discovery and development process. Currently, proximal tubule cell lines of human
origin such as RPTEC/TERT1 and HK-2 are used to understand the pathophysiology of
kidney diseases, therapeutic efficacy of drugs, and nephrotoxicity of compounds.
3. The purpose of the present study is to understand the metabolic enzymes
present in RPTEC/TERT1 and HK-2 cell lines that would help to interpret and
predict probable in vitro behavior of the molecule being tested. 4. We analyzed
the expression of phase I and II metabolizing enzymes of RPTEC/TERT1 and HK-2
cell lines. We found equal expression of CYP1B1, 2J2, 3A4, 3A5, UGT1A9, SULT2A1
and GSTA, higher expression of 2B6, 2D6, 4A11, 4F2, 4F8, 4F11, UGT2B7, SULT1E1 in
RPTEC/TERT1 and absence of GSTT in RPTEC/TERT1 compared to HK-2 at mRNA level.
Such differences can affect the outcome of in vitro nephrotoxicity prediction.
PMID- 27616668
TI - Pituitary lacks sexual dimorphism and displays reduced signal intensity on T1
weighted MRI in adolescents with histories of heavy prenatal alcohol exposure.
AB - Prenatal alcohol exposure can interfere with endocrine function and have sex
specific effects on behavior. Disrupted development of the pituitary gland, which
has been observed in rodent studies, may account for some of these effects. To
determine if gestational exposure to alcohol produces measureable changes in the
pituitary in human adolescents, we manually traced the pituitary in T1-weighted
structural magnetic resonance images (MRI) from adolescents with (15 males, 11
females) and without (16 males, 11 females) heavy prenatal alcohol exposure.
Pituitary gland volume and maximum signal intensity were examined for group
differences. Control female adolescents presented with significantly greater
pituitary volume compared to males, as has been previously reported. However,
this sexual dimorphism was absent in adolescents with histories of prenatal
alcohol exposure. Alcohol-exposed adolescents, regardless of sex, demonstrated
reduced pituitary maximum signal intensity compared to controls. The lack of a
sex difference in pituitary volumes within the alcohol-exposed group suggests
such exposure may interfere with adolescent typical sexual dimorphism of the
pituitary. Signal intensity in the posterior pituitary may reflect vasopressin
storage. Our findings suggest vasopressin activity should be evaluated in alcohol
exposed adolescents.
PMID- 27616669
TI - Mechanistic insights from resolving ligand-dependent kinetics of conformational
changes at ATP-gated P2X1R ion channels.
AB - Structural studies of P2X receptors show a novel U shaped ATP orientation
following binding. We used voltage clamp fluorometry (VCF) and molecular dynamics
(MD) simulations to investigate agonist action. For VCF the P2X1 receptor (P2X1R)
K190C mutant (adjacent to the agonist binding pocket) was labelled with the
fluorophore MTS-TAMRA and changes in fluorescence on agonist treatment provided a
real time measure of conformational changes. Studies with heteromeric channels
incorporating a key lysine mutation (K68A) in the ATP binding site demonstrate
that normally three molecules of ATP activate the receptor. The time-course of
VCF responses to ATP, 2'-deoxy ATP, 3'-deoxy ATP, Ap5A and alphabetameATP were
agonist dependent. Comparing the properties of the deoxy forms of ATP
demonstrated the importance of the 2' hydroxyl group on the ribose ring in
determining agonist efficacy consistent with MD simulations showing that it forms
a hydrogen bond with the gamma-phosphate oxygen stabilizing the U-shaped
conformation. Comparison of the recovery of fluorescence on agonist washout, with
channel activation to a second agonist application for the partial agonists Ap5A
and alphabetameATP, showed a complex relationship between conformational change
and desensitization. These results highlight that different agonists induce
distinct conformational changes, kinetics and recovery from desensitization at
P2X1Rs.
PMID- 27616670
TI - Progestins used in endocrine therapy and the implications for the biosynthesis
and metabolism of endogenous steroid hormones.
AB - Steroidogenesis refers to the de novo synthesis of steroid hormones from
cholesterol by a number of sequential enzyme catalysed reactions in the adrenal
and the gonads. In addition, circulating steroid hormone precursors are further
metabolised in selected peripheral tissues. It has been suggested that the
biosynthesis of endogenous steroid hormones can be modulated by progestins, used
widely by women in female reproductive medicine. However, as a number of
structurally diverse progestins with different pharmacological properties are
available, it is possible that these synthetic compounds may vary in their
effects on steroidogenesis. This review summarises the evidence indicating that
progestins influence the biosynthesis of steroid hormones in the adrenal and
gonads, as well as the metabolism of these endogenous hormones in the breast,
highlighting the limitations to the current knowledge and directions for future
research.
PMID- 27616667
TI - Carbon monoxide and anesthesia-induced neurotoxicity.
AB - The majority of commonly used anesthetic agents induce widespread neuronal
degeneration in the developing mammalian brain. Downstream, the process appears
to involve activation of the oxidative stress-associated mitochondrial apoptosis
pathway. Targeting this pathway could result in prevention of anesthetic toxicity
in the immature brain. Carbon monoxide (CO) is a gas that exerts biological
activity in the developing brain and low dose exposures have the potential to
provide neuroprotection. In recent work, low concentration CO exposures limited
isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice
and modulated oxidative stress within forebrain mitochondria. Because infants and
children are routinely exposed to low levels of CO during low-flow general
endotracheal anesthesia, such anti-oxidant and pro-survival cellular effects are
clinically relevant. Here we provide an overview of anesthesia-related CO
exposure, discuss the biological activity of low concentration CO, detail the
effects of CO in the brain during development, and provide evidence for CO
mediated inhibition of anesthesia-induced neurotoxicity.
PMID- 27616671
TI - Sox21 deletion in mice causes postnatal growth deficiency without physiological
disruption of hypothalamic-pituitary endocrine axes.
AB - The hypothalamic-pituitary axes are the coordinating centers for multiple
endocrine gland functions and physiological processes. Defects in the
hypothalamus or pituitary gland can cause reduced growth and severe short
stature, affecting approximately 1 in 4000 children, and a large percentage of
cases of pituitary hormone deficiencies do not have an identified genetic cause.
SOX21 is a protein that regulates hair, neural, and trophoblast stem cell
differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this
growth defect has not been described. We studied the expression of Sox21 in
hypothalamic-pituitary development and examined multiple endocrine axes in these
mice. We find no evidence of reduced intrauterine growth, food intake, or
physical activity, but there is evidence for increased energy expenditure in
mutants. In addition, despite changes in pituitary hormone expression,
hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants
may be a cause of non-endocrine short stature in humans.
PMID- 27616672
TI - Role of Divalent Metal Ions in Atypical Nonlinear Plasma Protein Binding Behavior
of Tigecycline.
AB - In typical nonlinear plasma protein binding (PPB) behavior, the free fraction
increases with increasing total concentrations. In contrast, when a drug exhibits
atypical nonlinear PPB behavior, the free fraction decreases with increasing
total concentrations. Tigecycline, a novel glycylcycline, exhibits atypical
nonlinear PPB behavior, but the mechanism of such behavior is currently unknown.
Because tigecycline can form complexes with metal ions, an interaction between
metal ion, tigecycline, and plasma proteins was hypothesized but not further
investigated. The current work explores the role of metal ions in the atypical
nonlinear PPB behavior of tigecycline and proposes a plausible mechanism of
atypical nonlinear PPB behavior. The addition of ethylenediaminetetraacetic acid
resulted in 10- to 30-fold higher unbound fractions, and the atypical behavior
was nullified. The saturation of ethylenediaminetetraacetic acid chelation, by
addition of excessive divalent metal ions, such as calcium and magnesium, led to
the return of the atypical nonlinear PPB behavior. Different possible mechanisms
were evaluated by simulation, and a plausible mechanism was proposed.
PMID- 27616673
TI - Differentiating between axonal damage and demyelination in healthy aging by
combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the
human corpus callosum at 7 T.
AB - Diffusion-tensor imaging and single voxel diffusion-weighted magnetic resonance
spectroscopy were used at 7T to explore in vivo age-related microstructural
changes in the corpus callosum. Sixteen healthy elderly (age range 60-71 years)
and 13 healthy younger controls (age range 23-32 years) were included in the
study. In healthy elderly, we found lower water fractional anisotropy and higher
water mean diffusivity and radial diffusivity in the corpus callosum, indicating
the onset of demyelination processes with healthy aging. These changes were not
associated with a concomitant significant difference in the cytosolic diffusivity
of the intra-axonal metabolite N-acetylaspartate (p = 0.12), the latter
representing a pure measure of intra-axonal integrity. It was concluded that the
possible intra-axonal changes associated with normal aging processes are below
the detection level of diffusion-weighted magnetic resonance spectroscopy in our
experiment (e.g., smaller than 10%) in the age range investigated. Lower axial
diffusivity of total creatine was observed in the elderly group (p = 0.058),
possibly linked to a dysfunction in the energy metabolism associated with a
deficit in myelin synthesis.
PMID- 27616675
TI - Darwinian evolution includes Lamarckian inheritance of acquired characters.
PMID- 27616674
TI - Assessing the suitability of summary data for two-sample Mendelian randomization
analyses using MR-Egger regression: the role of the I2 statistic.
AB - Background: : MR-Egger regression has recently been proposed as a method for
Mendelian randomization (MR) analyses incorporating summary data estimates of
causal effect from multiple individual variants, which is robust to invalid
instruments. It can be used to test for directional pleiotropy and provides an
estimate of the causal effect adjusted for its presence. MR-Egger regression
provides a useful additional sensitivity analysis to the standard inverse
variance weighted (IVW) approach that assumes all variants are valid instruments.
Both methods use weights that consider the single nucleotide polymorphism (SNP)
exposure associations to be known, rather than estimated. We call this the 'NO
Measurement Error' (NOME) assumption. Causal effect estimates from the IVW
approach exhibit weak instrument bias whenever the genetic variants utilized
violate the NOME assumption, which can be reliably measured using the F
statistic. The effect of NOME violation on MR-Egger regression has yet to be
studied. Methods: An adaptation of the I2 statistic from the field of meta
analysis is proposed to quantify the strength of NOME violation for MR-Egger. It
lies between 0 and 1, and indicates the expected relative bias (or dilution) of
the MR-Egger causal estimate in the two-sample MR context. We call it IGX2 . The
method of simulation extrapolation is also explored to counteract the dilution.
Their joint utility is evaluated using simulated data and applied to a real MR
example. Results: In simulated two-sample MR analyses we show that, when a causal
effect exists, the MR-Egger estimate of causal effect is biased towards the null
when NOME is violated, and the stronger the violation (as indicated by lower
values of IGX2 ), the stronger the dilution. When additionally all genetic
variants are valid instruments, the type I error rate of the MR-Egger test for
pleiotropy is inflated and the causal effect underestimated. Simulation
extrapolation is shown to substantially mitigate these adverse effects. We
demonstrate our proposed approach for a two-sample summary data MR analysis to
estimate the causal effect of low-density lipoprotein on heart disease risk. A
high value of IGX2 close to 1 indicates that dilution does not materially affect
the standard MR-Egger analyses for these data. Conclusions: : Care must be taken
to assess the NOME assumption via the IGX2 statistic before implementing standard
MR-Egger regression in the two-sample summary data context. If IGX2 is
sufficiently low (less than 90%), inferences from the method should be
interpreted with caution and adjustment methods considered.
PMID- 27616676
TI - Changes in Corneal Subbasal Nerve Morphology and Sensitivity During
Orthokeratology: Onset of Change.
AB - PURPOSE: To investigate changes in corneal subbasal nerve fiber density and
orientation during a 3-month orthokeratology (OK) lens wear period and their
relationship with concurrent changes in corneal sensitivity. METHODS: Sixteen
subjects wore overnight OK lenses for 90 days and were assessed at baseline, Day
30, and Day 90. Nerve images at the corneal apex and temporal mid-periphery were
captured from the right eye only using in vivo confocal microscopy and analyzed
to calculate nerve fiber density (NFD) and global nerve fiber orientation (GNFO).
Corneal sensitivity was measured using the Cochet-Bonnet aesthesiometer at
similar corneal locations. Control groups of non-lens (NL) wearing and
conventional rigid gas-permeable (GP) lens-wearing subjects were also examined.
RESULTS: Significant changes in NFD, GNFO and corneal sensitivity were observed
during OK lens wear over the study period. In the central cornea, both NFD and
corneal sensitivity decreased by Day 30, with further reductions at Day 90.
Reduced NFD was associated with reduced corneal sensitivity. In the mid
peripheral cornea only, GNFO was rotated in a clockwise direction at Day 30, with
further rotation at Day 90. Corneal sensitivity reduction plateaued by Day 30. In
the GP lens-wearing subjects, only corneal sensitivity decreased by Day 30 at
both corneal locations. No changes were observed in the NL control subjects.
CONCLUSIONS: Alterations in corneal nerve morphology occur rapidly with
commencement of OK lens wear and appear to underpin functional sensitivity loss.
Nerve fiber orientation can provide a useful index for changes in corneal nerve
morphology.
PMID- 27616677
TI - Binge-eating disorder and the outcome of bariatric surgery in a prospective,
observational study: Two-year results.
AB - OBJECTIVE: A previous study reported that preoperative binge-eating disorder
(BED) did not attenuate weight loss at 12 months after bariatric surgery. This
report extends the authors' prior study by examining weight loss at 24 months.
METHODS: A modified intention-to-treat population was used to compare 24-month
changes in weight among 59 participants treated with bariatric surgery,
determined preoperatively to be free of a current eating disorder, with changes
in 33 surgically treated participants with BED. Changes were also compared with
49 individuals with obesity and BED who sought lifestyle modification for weight
loss. Analyses included all available data points and were adjusted for
covariates. RESULTS: At month 24, surgically treated patients with BED
preoperatively lost 18.6% of initial weight, compared with 23.9% for those
without BED (P = 0.049). (Mean losses at month 12 had been 21.5% and 24.2%,
respectively; P = 0.23.) Participants with BED who received lifestyle
modification lost 5.6% at 24 months, significantly less than both groups of
surgically treated patients (P < 0.001). CONCLUSIONS: These results suggest that
preoperative BED attenuates long-term weight loss after bariatric surgery. We
recommend that patients with this condition, as well as other eating
disturbances, receive adjunctive behavioral support, the timing of which remains
to be determined.
PMID- 27616680
TI - Intra-familial variability associated with recessive RYR1 mutation diagnosed
prenatally by exome sequencing.
AB - OBJECTIVE: To determine the underlying molecular aetiology in a non
consanguineous Irish family who have had three fetal losses because of a primary
myopathy characterised by fetal akinesia, arthrogryposis multiplex, bilateral
pulmonary hypoplasia and reduced muscle bulk. METHODS: Fetal DNA extracted from
amniotic cells was whole genome amplified and subjected to whole exome
sequencing. RESULTS: Whole exome sequencing identified compound heterozygous
variants in RYR1 as the cause of the lethal myopathy in this family. All three
fetuses were compound heterozygous for a paternally inherited missense variant
(c.2113G > A; p.Gly705Arg) and a novel maternally inherited truncating frameshift
deletion (c.8843delC; p.Ser2948Cysfs*58). This family did not have the classic
cores and fibre type disproportion typically associated with RYR1 mutation. The
RYR1 exome finding was made during the couple's third pregnancy and enabled
prenatal genetic testing to be undertaken. CONCLUSION: We show that recessive
RYR1 mutations can be associated with significant intra-familial variability in
clinical presentation which can complicate prediction of clinical outcome. RYR1
mutations can also cause diverse muscle pathologies which thwarts diagnosis. This
study demonstrates the impact that exome-based diagnoses can have for families
with lethal disorders. (c) 2016 John Wiley & Sons, Ltd.
PMID- 27616679
TI - Regulatory properties of statins and rho gtpases prenylation inhibitiors to
stimulate melanoma immunogenicity and promote anti-melanoma immune response.
AB - Melanoma is a highly lethal cutaneous tumor, killing affected patients through
development of multiple poorly immunogenic metastases. Suboptimal activation of
immune system by melanoma cells is often due to molecular modifications occurring
during tumor progression that prevent efficient recognition of melanoma cells by
immune effectors. Statins are HMG-CoA reductase inhibitors, which block the
mevalonate synthesis pathway, used by millions of people as hypocholesterolemic
agents in cardiovascular and cerebrovascular diseases. They are also known to
inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases
are regarded as molecular switches that regulate a wide spectrum of cellular
functions and their dysfunction has been characterized in various oncogenic
process notably in melanoma progression. Moreover, these molecules can modulate
the immune response. Since 10 years we have demonstrated that Statins and other
Rho GTPases inhibitors are critical regulators of molecules involved in adaptive
and innate anti-melanoma immune response. In this review we summarize our major
observations demonstrating that these pharmacological agents stimulate melanoma
immunogenicity and suggest a potential use of these molecules to promote anti
melanoma immune response.
PMID- 27616681
TI - Response to Letter to the Editor: 'Use of preoperative comorbidity scores to
predict mortality after total arthroplasty'.
PMID- 27616678
TI - Cell- and region-specific expression of depression-related protein p11 (S100a10)
in the brain.
AB - P11 (S100a10), a member of the S100 family of proteins, has widespread
distribution in the vertebrate body, including in the brain, where it has a key
role in membrane trafficking, vesicle secretion, and endocytosis. Recently, our
laboratory has shown that a constitutive knockout of p11 (p11-KO) in mice results
in a depressive-like phenotype. Furthermore, p11 has been implicated in major
depressive disorder (MDD) and in the actions of antidepressants. Since depression
affects multiple brain regions, and the role of p11 has only been determined in a
few of these areas, a detailed analysis of p11 expression in the brain is
warranted. Here we demonstrate that, although widespread in the brain, p11
expression is restricted to distinct regions, and specific neuronal and
nonneuronal cell types. Furthermore, we provide comprehensive mapping of p11
expression using in situ hybridization, immunocytochemistry, and whole-tissue
volume imaging. Overall, expression spans multiple brain regions, structures, and
cell types, suggesting a complex role of p11 in depression. J. Comp. Neurol.
525:955-975, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27616683
TI - Use of preoperative comorbidity scores to predict mortality after total
arthroplasty.
PMID- 27616682
TI - Factors that influence outcome in experimental osteoarthritis.
AB - OBJECTIVE: Osteoarthritis (OA) is the most common joint disease but an effective
pharmacological therapy has not been developed yet. To identify targets for
treatment and ways to interfere with OA development and progression both
spontaneous and induced OA models are still needed. In this narrative review it
is discussed what variables can be identified that lead to variation in OA animal
model studies. DESIGN: Literature was screened (Pubmed) with the following terms;
OA animal models in combination with species, age, strain, gender/sex, housing,
diet, fighting, circadian rhythm, transgenic. Relevant articles were selected and
additional papers were searched for and read for specific subtopics. RESULTS:
Studies with OA models are subject to a multitude of variables, stimuli and
conditions that can influence the outcome of an animal experiment. Outcome will
depend on amongst others; the model used, species and strain, age, gender, diet,
housing conditions, circadian rhythm, timing of intervention, stress levels and
activity. Variations in these variables can account for discrepancies between OA
model experiments, intervention studies and conclusions. CONCLUSION: To improve
OA animal model research, investigators should be aware of all the stimuli and
conditions that can interfere with disease development and disease intervention
and take these into account in their study design and execution.
PMID- 27616684
TI - Infrapatellar fat pad aggravates degeneration of acute traumatized cartilage: a
possible role for interleukin-6.
AB - OBJECTIVES: The infrapatellar fat pad (IPFP), which is located underneath the
patella, close to cartilage surfaces, functions in distributing mechanical load
and has been shown to produce cytokines. This study aims to assess the
involvement of the IPFP in the progression of post-traumatic osteoarthritis (OA)
through investigating the crosstalk between the IPFP and injured cartilage in
vitro. METHODS: A single blunt impact (36 MPa) on healthy bovine articular
cartilage explants was used to generate traumatized cartilage. Conditioned media
from IPFP and traumatized cartilage (FP-CM and TC-CM) were prepared separately.
After culturing in FP-CM, the posttraumatic cartilage explants were analyzed for
expression of cartilage degeneration associated genes and secretion of the
interleukin (IL)-6, into the culture medium. The effect of traumatized cartilage
on IPFP was studied by treating IPFP-derived adipocytes and IPFP adipose-derived
stromal cells (ADSC) with TC-CM followed by analysis of cytokine expression.
RESULTS: FP-CM aggravated glycosaminoglycan (GAG) release in traumatized
cartilage, but did not significantly affect healthy cartilage. FP-CM raised gene
expression of cyclooxygenase-2, inducible nitric oxide synthase, and IL-6 in
traumatized cartilage explants, and lowered expression of tissue inhibitor of
metalloproteinases-1, 2, 3, compared to non-conditioned medium. Of particular
significance is that medium IL-6 levels increased substantially in both FP-CM and
FP-CM treated traumatized cartilage cultures. Extrinsic IL-6 treatment of
traumatized cartilage simulated part of the effects of FP-CM. TC-CM elevated
levels of IL-6 expression in IPFP derived adipocytes and ADSCs. CONCLUSIONS: IPFP
aggravates post-traumatized cartilage degeneration, and IL-6 is a candidate
tissue degeneration mediator.
PMID- 27616685
TI - The knee adduction moment and knee osteoarthritis symptoms: relationships
according to radiographic disease severity.
AB - OBJECTIVE: To investigate relationships between external knee adduction moment
parameters (KAM) and osteoarthritis (OA) symptoms according to disease severity.
DESIGN: 164 participants with symptomatic medial knee OA were included.
Radiographic severity was graded by (1) Kellgren & Lawrence (KL) scale (Grade 2,
n = 49; Grade, n = 52; Grade 4, n = 63) and; (2) medial tibiofemoral joint space
narrowing (JSN) (Grade 1, n = 47; Grade 2, n = 50; Grade 3, n = 67). KAM-related
parameters (peak KAM, KAM impulse and cumulative load) were determined from three
dimensional gait analysis and pedometry. Cumulative load was determined by
multiplying KAM impulse by the average number of steps/day recorded over at least
5 days. Symptoms were assessed via numeric rating scale ((NRS), pain) and Western
Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain and physical
function). Relationships between KAM parameters (independent variables) and
symptoms (dependent variables) were evaluated by radiographic severity using
linear models, adjusting for covariates. RESULTS: In mild disease (either KL
Grade 2 or JSN Grade 1), there were no associations between KAM and symptoms. In
moderate disease of KL Grade 3, higher KAM impulse was associated with greater
WOMAC pain. In severe disease (KL Grade 4), higher KAM impulse was associated
with less WOMAC pain (KL Grade 4), while higher peak KAM was associated with
better function (KL Grade 4). Higher cumulative knee adduction load was
associated with less pain on both NRS and WOMAC (JSN Grade 3) as well as better
function (both JSN Grade 3 and KL Grade 4). CONCLUSIONS: Relationships between
KAM-related parameters and symptoms differ according to underlying radiographic
OA severity.
PMID- 27616686
TI - Soil-transmitted Helminth Infections in Schoolchildren of Laguna de Perlas
(Nicaragua).
AB - Soil-transmitted helminth (STH) prevalence, intensity, polyparasitism and co
infections in 425 children from 3 schools of Laguna de Perlas (Nicaragua) were
investigated. Single stool samples were analysed by the formalin-ether method and
the Kato-Katz. A total of 402 (94.6%) children were infected. Trichuris trichiura
308 (72.4%), Ascaris lumbricoides 115 (27.1%) and Hookworms 54 (12.7%) were the
most prevalent STHs. Polyparasitism (322; 75.8%) with two species was most
prevalent (109; 25.6%). T. trichiura with A. lumbricoides (19.3%) and T.
trichiura with Hookworm (6.8%) were the most common combinations. Positive
associations were observed between T. trichiura and A. lumbricoides and T.
trichiura and Hookworm (p = 0.0001). Highest Hookworm intensities appeared when
three STH co-infections occurred. Moderate- heavy STH intensities appear in up to
42.1% in trichuriasis, 57.5% in ascariasis and 11.1% in Hookworm infections.
Integrated control interventions covering children need to be implemented mainly
in a rural environment.
PMID- 27616687
TI - Identifying the Neural Substrates of Procrastination: a Resting-State fMRI Study.
AB - Procrastination is a prevalent problematic behavior that brings serious
consequences to individuals who suffer from it. Although this phenomenon has
received increasing attention from researchers, the underpinning neural
substrates of it is poorly studied. To examine the neural bases subserving
procrastination, the present study employed resting-state fMRI. The main results
were as follows: (1) the behavioral procrastination was positively correlated
with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the
parahippocampal cortex (PHC), while negatively correlated with that of the
anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the
anterior medial prefrontal cortex and the posterior cingulate cortex was
positively associated with procrastination. (3) The connectivity between vmPFC
and several other regions, such as the dorsomedial prefrontal cortex, the
bilateral inferior prefrontal cortex showed a negative association with
procrastination. These results suggested that procrastination could be attributed
to, on the one hand, hyper-activity of the default mode network (DMN) that
overrides the prefrontal control signal; while on the other hand, the failure of
top-down control exerted by the aPFC on the DMN. Therefore, the present study
unravels the biomarkers of procrastination and provides treatment targets for
procrastination prevention.
PMID- 27616688
TI - Diabetes increases the risk of an appendectomy in patients with antibiotic
treatment of noncomplicated appendicitis.
AB - BACKGROUND: This retrospective cohort study examined whether diabetic patients
have a higher risk for recurrent appendicitis during a 1-year follow-up period
after successful antibiotic treatment for patients with acute uncomplicated
appendicitis than nondiabetic patients using a population-based database.
METHODS: We included 541 appendicitis patients who received antibiotic treatment
for acute appendicitis. We individually tracked each patient for a 1-year period
to identify those who subsequently underwent an appendectomy during the follow-up
period. RESULTS: Cox proportional hazard regressions suggested that the adjusted
hazard ratio of an appendectomy during the 1-year follow-up period was 1.75 for
appendicitis patients with diabetes than appendicitis patients without diabetes.
We found that among females, the adjusted hazard ratio of an appendectomy was
2.18 for acute appendicitis patients with diabetes than their counterparts
without diabetes. However, we failed to observe this relationship in males.
CONCLUSIONS: We demonstrated a relationship between diabetes and a subsequent
appendectomy in females who underwent antibiotic treatment for noncomplicated
appendicitis.
PMID- 27616689
TI - Invited commentary on "Acute care surgery: trauma, critical care, EGS ... and
preventative health?"
PMID- 27616690
TI - Time trends in the incidence, prevalence, and severity of rheumatoid arthritis: A
systematic literature review.
AB - INTRODUCTION: Rheumatoid arthritis (RA) generates a heavy socioeconomic burden.
The ability to predict the frequency and severity of socioeconomic effects due to
RA is crucial to the development of public health policies. OBJECTIVE: To conduct
a systematic literature review of data on the prevalence, incidence, and severity
of RA. METHODS: Medline, EMBASE, the Cochrane Library, and online American
College of Rheumatology communications were searched for articles on the
prevalence and incidence of RA, as well as on selected severity and activity
criteria. Relevant articles were then selected by two investigators. RESULTS:
Frequency data are conflicting. No proof exists from cohort studies that the
incidence of RA has changed over time. Overall, the prevalence of RA is stable or
on the rise. Studies consistently demonstrated a decrease in severity over time,
with lower activity, fewer extraarticular manifestations, a diminished need for
surgery to treat joint destruction, and less severe radiological changes. The
excess mortality, in contrast, despite a trend toward a decrease over time,
remains significant. CONCLUSION: The activity and deleterious effects of RA have
diminished over time, in conjunction with recent therapeutic advances (new drugs
and improved patient selection). However, there seems to be no decrease in the
frequency of RA, which continues to induce significant excess mortality.
PMID- 27616691
TI - pH and heat induced structural changes of chicken ovalbumin in relation with
antigenic properties.
AB - Ovalbumin is the major egg white protein known to induce allergic reactions in
humans. A comprehensive evaluation of the structural and antigenicity features of
ovalbumin subjected to different pH and heat treatments was performed by
combining fluorescence spectroscopic measurements, ELISA and in silico
prediction. The intrinsic fluorescence spectra indicated modification of the
ovalbumin tertiary structure depending on pH and applied temperature. The heat
treatment caused the alteration of ovalbumin structure, which exhibited gradual
hydrophobic exposure. The in depths check of ovalbumin molecular model, after
performing molecular dynamics simulations, indicated the slight transition toward
a typical beta-strand dominant structure with the temperature increase. Moreover
the immunoenzymatic test was employed to estimate the effect of the pH and
thermal treatment on the stability of ovalbumin epitopes. Only a 5.5% reduction
of the residual antigenicity was observed when heat treating the ovalbumin
samples at pH 7.0, whereas a significant reduction (over 82%) of the antigenicity
was obtained at pH 9.5 and temperatures over 80 degrees C. Both pH and thermal
treatment affected the conformation of ovalbumin. The reduced recognition of the
modified native ovalbumin by specific antibodies at alkaline pH is most probably
a consequence of significant changes in the local conformation of the epitopes.
PMID- 27616692
TI - Sodium alginate conjugated graphene oxide as a new carrier for drug delivery
system.
AB - The biomedical applications of graphene-based materials, including drug delivery,
have grown rapidly in the past few years. The aim of this present study is to
enhance the efficiency and specificity of anticancer drug delivery and realize
intelligently controlled release and targeted delivery. Graphene oxide (GO) was
first prepared from purified natural graphite according to a modified Hummers'
method. Then GO was functionalized with adipic acid dihydrazide to introduce
amine groups, and sodium alginate (SA) was covalently conjugated to GO by the
formation of amide bonds. The resulting GO-SA conjugate was characterized and
used as a carrier to encapsulate the anticancer drug doxorubicin hydrochloride
(DOX.HCl) to study in vitro release behavior. The maximum loading capacity of DOX
on GO-SA was 1.843mg/mg and the drug release rate under tumor cell
microenvironment of pH 5.0 was significantly higher than that under physiological
conditions of pH 6.5 and 7.4. Methylthiazol tetrazolium (MTT) assay was applied
to evaluate the Hela cells and NIH-3T3 cells cytotoxicity of GO-SA. Results
showed that GO-SA had no obvious toxicity and GO-SA/DOX exhibits notable
cytotoxicity to Hela cells. Cell uptake studies indicated that GO-SA could
specifically transport the DOX into Hela cells over-expressing CD44 receptors and
showed enhanced toxicity.
PMID- 27616693
TI - Optimization and antioxidant activity of polysaccharides from Plantago depressa.
AB - Polysaccharide from the herb of Plantago depressa (PDP) was obtained through
ethanol precipitation preceded by a water extraction step. The optimum extraction
yield of 5.68+/-0.46% was obtained with the treatment of raw material in water
(w/v, 1:25.34) at 80.44 degrees C during 1.97h, 3.28 times. Under these
conditions, obtained yield value was in total agreement with value predicted by
the model executed by Box-Behnken design (BBD). Following analysis by IR, HPLC
UV, MS and 1H NMR, the composition of PDP was found to be l-rhamnose, galactose,
arabinose, glucose and d-galacturonic acid. The maximum tolerated dose of PDP was
10g/kg. The antioxidant activity of PDP was investigated using five tests and it
was found that PDP was able to scavenge hydroxyl, DPPH and ABTS radicals, besides
their beta-carotene bleaching inhibitory activity. In particular, in the test of
beta-carotene bleaching inhibition, PDP displayed higher activity than Vitamin C.
PMID- 27616694
TI - Inhibitory effect of verbascoside on xanthine oxidase activity.
AB - In this study, we analyzed the inhibitory effect of verbascoside against xanthine
oxidase (XOD) in vitro by using animal model and in vivo by direct inhibition
assay. Results showed that verbascoside could reduce uric acid in rat serum and
inhibit XOD activity in rat liver. The IC50 value of restraining XOD activity was
81.11mgmL-1. Fluorescence chromatographic analysis and circular dichroism
spectroscopy indicated that the secondary structures of XOD were changed after
incubation with verbascoside. The docking simulation showed that verbascoside
could enter into the active site of XOD and form hydrogen bonding with amino acid
residues (such as Lys-1045, Arg-880, Arg-912, Glu-1261 and Gln-1194). The results
suggested that verbascoside, which is a naturally occurring water-soluble
antioxidant, could be a potential low-toxicity XOD inhibitor for hyperuricemia
treatment.
PMID- 27616695
TI - Rapid Detection of Enterobacter Sakazakii in milk Powder using amino modified
chitosan immunomagnetic beads.
AB - Chitosan immunomagnetic beads (CIBs) were first prepared through converting
hydroxyl groups of natural polymer material-chitosan into amino groups using
epichlorohydrin and ethylenediamine as modification agent and then coupling with
polyclonal antibodies of Enterobacter sakazakii using glutaraldehyde as cross
linking agent. The beads before coupling with antibodies were characterized by
magnetic property measurement, FTIR, SEM and XRD technologies. In the assay a
natural polysaccharide-chitosan, which has good biological and chemical
properties such as non-toxicity, biocompatibility and high chemical reactivity
was first used for synthesis of immunomagnetic beads. The detection method first
established in this paper that combined the beads with chromogenic medium
together to rapid detect E. sakazakii in milk powder could greatly improve the
detection specificity and working efficiency. The beads exhibited a maximum
capturing capacity of 1*106cfu/g with the detection sensitivity of 4cfu/g. The
results demonstrate that the assay is a straightforward, specific and sensitive
alternative for rapid detection of E.sakazakii in food matrix. The total analysis
time was as little as about 25h, which greatly shorten the detection time. The
method can provides new ideas not only to preparation technique of immunomagnetic
beads but to imunne detection technique in food safety.
PMID- 27616696
TI - Effects of Ganoderma lucidum polysaccharides on chronic pancreatitis and
intestinal microbiota in mice.
AB - This study manifested the effects of polysaccharides from Ganoderma lucidum
strain S3 (GLP S3) on chronic pancreatitis (CP) therapy and intestinal microbiota
modulation in mice induced by diethyldithiocarbamate (DDC). The GLPS3 was
prepared from cultured mycelium and markedly alleviated the pancreatitis in mice
through decreasing lipase, AMS, IFN-gamma and TNF-alpha level as well as
increasing SOD and total antioxidant activity. Furthermore, high throughput
sequencing analysis revealed that GLPS3 altered the composition and diversity of
intestinal microbiota, especially, decreased the relative abundance of phylum
Bacteroidetes and increased that of phylum Firmictutes. At the genus level,
supplementation of GLPS3 increased the relative abundance of the beneficial
bacteria such as Lactobacillales, Roseburia and Lachnospiraceae. These results
disclosed the potential therapy mechanism of GLPS3 on chronic pancreatitis might
be intestinal microbiota dependent.
PMID- 27616698
TI - Virchow triad and beyond in atrial fibrillation.
PMID- 27616697
TI - The one that got away: A leadless pacemaker embolizes to the lungs.
PMID- 27616699
TI - Biology and pathogenesis of Naegleria fowleri.
AB - Naegleria fowleri is a protist pathogen that can cause lethal brain infection.
Despite decades of research, the mortality rate related with primary amoebic
meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass
through the nose to enter the central nervous system killing the host within
days, making it one of the deadliest opportunistic parasites. Accordingly, we
present an up to date review of the biology and pathogenesis of N. fowleri and
discuss needs for future research against this fatal infection.
PMID- 27616702
TI - Radioligand therapy with 177Lu-PSMA-617 of metastatic prostate cancer has already
been arrived in clinical use.
PMID- 27616700
TI - Concerted functions of Streptococcus gordonii surface proteins PadA and Hsa
mediate activation of human platelets and interactions with extracellular matrix.
AB - A range of Streptococcus bacteria are able to interact with blood platelets to
form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human
oral cavity and amongst the common pathogens isolated from subjects with
infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence
protein A (PadA), in S. gordonii mediate adherence and activation of platelets.
In this study, we demonstrate that PadA binds activated platelets and that an NGR
(Asparagine-Glycine-Arginine) motif within a 657 amino acid residue N-terminal
fragment of PadA is responsible for this, together with two other integrin-like
recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate
binding of S. gordonii to cellular fibronectin and vitronectin, and to promote
formation of biofilms. Evidence is presented that PadA and Hsa are each reliant
on the other's active presentation on the bacterial cell surface, suggesting
cooperativity in functions impacting both colonization and pathogenesis.
PMID- 27616701
TI - Assessing electronic health record phenotypes against gold-standard diagnostic
criteria for diabetes mellitus.
AB - Objective: We assessed the sensitivity and specificity of 8 electronic health
record (EHR)-based phenotypes for diabetes mellitus against gold-standard
American Diabetes Association (ADA) diagnostic criteria via chart review by
clinical experts. Materials and Methods: We identified EHR-based diabetes
phenotype definitions that were developed for various purposes by a variety of
users, including academic medical centers, Medicare, the New York City Health
Department, and pharmacy benefit managers. We applied these definitions to a
sample of 173 503 patients with records in the Duke Health System Enterprise Data
Warehouse and at least 1 visit over a 5-year period (2007-2011). Of these
patients, 22 679 (13%) met the criteria of 1 or more of the selected diabetes
phenotype definitions. A statistically balanced sample of these patients was
selected for chart review by clinical experts to determine the presence or
absence of type 2 diabetes in the sample. Results: The sensitivity (62-94%) and
specificity (95-99%) of EHR-based type 2 diabetes phenotypes (compared with the
gold standard ADA criteria via chart review) varied depending on the component
criteria and timing of observations and measurements. Discussion and Conclusions:
Researchers using EHR-based phenotype definitions should clearly specify the
characteristics that comprise the definition, variations of ADA criteria, and how
different phenotype definitions and components impact the patient populations
retrieved and the intended application. Careful attention to phenotype
definitions is critical if the promise of leveraging EHR data to improve
individual and population health is to be fulfilled.
PMID- 27616703
TI - Spinal WNT pathway contributes to remifentanil induced hyperalgesia through
regulating fractalkine and CX3CR1 in rats.
AB - BACKGROUND: Tremendous experimental and clinical studies identify that
remifentanil anesthesia might elicit postoperative opioid-induced hyperalgesia
(OIH) and aggravate nociceptive hypersensitivity, whereas definite mechanisms
remain equivocal. WNT signaling and fractalkine pathway have been manifested to
participate in varieties of pain pathogenesis, respectively, but no report is on
whether they could lead to OIH. This study intended to investigate the effect of
WNT3a/beta-catenin on fractalkine and its receptor CX3CR1 in OIH in rats model of
incision pain. METHODS: A WNT scavenger Fz-8/Fc and a neutralizing antibody
against CX3CR1 (anti-CX3CR1) were injected intrathecally after remifentanil
infusion. Exogenous WNT agonist delivery was utilized in naive rats. PWT and PWL
were documented for postsurgical 48h to assess mechanical and thermal
hyperalgesia. Also, expressions of WNT3a, FZ1, FZ8, beta-catenin, fractalkine and
CX3CR1 in spinal dorsal horn were measured by Western blot and RT-qPCR after
nociceptive testing. RESULTS: We found that postsurgical mechanical and thermal
hyperalgesia could be engendered after remifentanil exposure, which was
accompanied by a dramatical rise of spinal WNT3a, FZ8, beta-catenin, fractalkine
and CX3CR1 levels. Moreover, OIH was attenuated by intrathecal application of Fz
8/Fc and anti-CX3CR1. Up-regulation of spinal fractalkine and CX3CR1 expression
after remifentanil anesthesia was reversed by Fz-8/Fc. Also, WNT agonist
administration could directly generate hypernociception and elevate
fractalkine/CX3CR1 level in naive rats, which was prevented by anti-CX3CR1.
CONCLUSION: These present findings demonstrated that the involvement of spinal
WNT3a/FZ8/beta-catenin in OIH through modulating fractalkine/CX3CR1 in rats.
PMID- 27616704
TI - Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian
Girardia tigrina.
AB - Nicotine is one of the most addictive drugs abused by humans. Our laboratory and
others have demonstrated that nicotine decreases motility and induces seizure
like behavior in planarians (pSLM, which are vigorous writhing and bending of the
body) in a concentration-dependent manner. Nicotine also induces withdrawal-like
behaviors in these worms. Cotinine is the major nicotine metabolite in humans,
although it is not the final product of nicotine metabolism. Cotinine is mostly
inactive in vertebrate nervous systems and is currently being explored as a
molecule which possess most of nicotine's beneficial effects and few of its
undesirable ones. It is not known whether cotinine is a product of nicotine
metabolism in planarians. We found that cotinine by itself does not seem to
elicit any behavioral effects in planarians up to a concentration of 1mM. We also
show that cotinine antagonizes the aforementioned nicotine-induced motility
decrease and also decreases the expression of nicotine-induced pSLMs in a
concentration-dependent manner. Also cotinine prevents the manifestation of some
of the withdrawal-like behaviors induced by nicotine in our experimental
organism. Thus, we obtained evidence supporting that cotinine antagonizes
nicotine in this planarian species. Possible explanations include competitive
binding of both compounds at overlapping binding sites, at different nicotinic
receptor subtypes, or maybe allosteric interactions.
PMID- 27616705
TI - Cerebral dopamine neurotrophic factor alleviates Abeta25-35-induced endoplasmic
reticulum stress and early synaptotoxicity in rat hippocampal cells.
AB - Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease,
and early stage AD is characterized by synaptic dysfunction generally ascribed to
soluble oligomers of amyloid-beta (Abeta). Neurotrophic factors are promising for
AD treatment and are integrally involved in neuronal growth, survival and
maintenance. Cerebral dopamine neurotrophic factor (CDNF) was recently discovered
to have beneficial effects on long-term memory. The present study explored the
synaptoprotective effects of CDNF in Abeta-treated primary hippocampal cells.
Immunofluorescent analysis of synaptophysin and postsynaptic density protein 95
(PSD95) puncta densities in the group of pretreatment with CDNF before Abeta
exposure revealed significant improvements compared to Abeta group. In addition,
pretreatment with CDNF reduced the expression levels of endoplasmic reticulum
(ER) stress-related proteins, including Bip (also known as GRP78),
phosphorylation of eukaryotic translation initiation factor 2 subunit alpha
(peIF2alpha), phosphorylation of c-Jun N-terminal kinase (pJNK), and cleaved
caspase 3, which are increased by Abeta treatment at early stage. Our results
revealed protective effects of CDNF on Abeta-induced synaptotoxicity and ER
stress, implying that CDNF may protect against Abeta-induced synaptotoxicity
through suppression of ER stress. CDNF could be a potential drug candidate for
early AD treatment.
PMID- 27616706
TI - Adjunctive Corticosteroids for Pneumocystis jirovecii Pneumonia in Non-HIV
infected Patients: A Systematic Review and Meta-analysis of Observational
Studies.
AB - INTRODUCTION: The clinical benefits of adjunctive corticosteroids for
Pneumocystis jirovecii (P. jirovecii) pneumonia in patients not infected with the
human immunodeficiency virus (HIV) has not been evaluated by meta-analysis.
METHODS: We conducted a systematic review of published studies describing the
effects of adjunctive corticosteroids on outcome in non-HIV P. jirovecii
pneumonia patients. Two investigators independently searched the PubMed and
Cochrane databases for eligible articles written in English. A meta-analysis was
performed using a random-effects model for measuring mortality as the primary
outcome, and the need for intubation or mechanical ventilation as the secondary
outcome. RESULTS: Seven observational studies were eligible. In these studies,
adjunctive corticosteroids did not affect mortality in non-HIV patients (odds
ratio [OR] 1.26; 95% CI 0.60-2.67) and there was no beneficial effect in patients
with severe hypoxemia (PaO2<70mmHg) (OR 0.90; 95% CI 0.44-1.83). No significant
effect on the secondary outcome was observed (OR 1.34; 95% CI 0.44-4.11).
CONCLUSIONS: Although the studies were observational, meta-analysis showed that
adjunctive corticosteroids did not improve the outcome of P. jirovecii pneumonia
in non-HIV patients. The results warrant a randomized controlled trial.
PMID- 27616708
TI - ImmuneDB: a system for the analysis and exploration of high-throughput adaptive
immune receptor sequencing data.
AB - : As high-throughput sequencing of B cells becomes more common, the need for
tools to analyze the large quantity of data also increases. This article
introduces ImmuneDB, a system for analyzing vast amounts of heavy chain variable
region sequences and exploring the resulting data. It can take as input raw
FASTA/FASTQ data, identify genes, determine clones, construct lineages, as well
as provide information such as selection pressure and mutation analysis. It uses
an industry leading database, MySQL, to provide fast analysis and avoid the
complexities of using error prone flat-files. AVAILABILITY AND IMPLEMENTATION:
ImmuneDB is freely available at http://immunedb.comA demo of the ImmuneDB web
interface is available at: http://immunedb.com/demo CONTACT:
Uh25@drexel.eduSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27616707
TI - DM-BLD: differential methylation detection using a hierarchical Bayesian model
exploiting local dependency.
AB - MOTIVATION: The advent of high-throughput DNA methylation profiling techniques
has enabled the possibility of accurate identification of differentially
methylated genes for cancer research. The large number of measured loci
facilitates whole genome methylation study, yet posing great challenges for
differential methylation detection due to the high variability in tumor samples.
RESULTS: We have developed a novel probabilistic approach, D: ifferential M:
ethylation detection using a hierarchical B: ayesian model exploiting L: ocal D:
ependency (DM-BLD), to detect differentially methylated genes based on a Bayesian
framework. The DM-BLD approach features a joint model to capture both the local
dependency of measured loci and the dependency of methylation change in samples.
Specifically, the local dependency is modeled by Leroux conditional
autoregressive structure; the dependency of methylation changes is modeled by a
discrete Markov random field. A hierarchical Bayesian model is developed to fully
take into account the local dependency for differential analysis, in which
differential states are embedded as hidden variables. Simulation studies
demonstrate that DM-BLD outperforms existing methods for differential methylation
detection, particularly when the methylation change is moderate and the
variability of methylation in samples is high. DM-BLD has been applied to breast
cancer data to identify important methylated genes (such as polycomb target genes
and genes involved in transcription factor activity) associated with breast
cancer recurrence. AVAILABILITY AND IMPLEMENTATION: A Matlab package of DM-BLD is
available at http://www.cbil.ece.vt.edu/software.htm CONTACT:
Xuan@vt.eduSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27616709
TI - D-VASim: an interactive virtual laboratory environment for the simulation and
analysis of genetic circuits.
AB - : Simulation and behavioral analysis of genetic circuits is a standard approach
of functional verification prior to their physical implementation. Many software
tools have been developed to perform in silico analysis for this purpose, but
none of them allow users to interact with the model during runtime. The runtime
interaction gives the user a feeling of being in the lab performing a real world
experiment. In this work, we present a user-friendly software tool named D-VASim
(Dynamic Virtual Analyzer and Simulator), which provides a virtual laboratory
environment to simulate and analyze the behavior of genetic logic circuit models
represented in an SBML (Systems Biology Markup Language). Hence, SBML models
developed in other software environments can be analyzed and simulated in D
VASim. D-VASim offers deterministic as well as stochastic simulation; and differs
from other software tools by being able to extract and validate the Boolean logic
from the SBML model. D-VASim is also capable of analyzing the threshold value and
propagation delay of a genetic circuit model. AVAILABILITY AND IMPLEMENTATION: D
VASim is available for Windows and Mac OS and can be downloaded from
bda.compute.dtu.dk/downloads/. CONTACT: haba@dtu.dk, jama@dtu.dk.
PMID- 27616710
TI - Stress differentially regulates brain expression of corticotropin-releasing
factor in binge-like eating prone and resistant female rats.
AB - The expression of corticotropin-releasing factor (CRF), a neuropeptide that
regulates endocrine and behavioral responses to stress, was assessed in the brain
in rats prone or resistant to stress-induced binge-like eating of sucrose. Female
Sprague-Dawley rats were subjected to unpredictable intermittent 1-h access to
sucrose in non-stressful conditions or after exposure to three foot shock stress
sessions. Experimental sessions were performed at metestrus, diestrus, and
proestrus. The rats were assigned to the binge-like eating prone (BEP) or the
binge-like eating resistant (BER) phenotypes according to the rats' persistently
high or low sucrose intake following three stress sessions. The BEP rats
displayed elevated consumption of sucrose in non-stressful conditions and an
additional significant increase in sucrose intake in response to stress.
Conversely, the BER rats showed lower sucrose intake in non-stressful conditions,
and stress did not increase sucrose intake in this phenotype. The brain
expression of CRF mRNA and plasma corticosterone levels were assessed 30 min
after the last stress session at the diestrous phase of the estrous cycle. Stress
triggered a significant increase in plasma corticosterone levels and strongly
increased CRF mRNA expression in the paraventricular hypothalamic nucleus in the
BER but not in the BEP rats. However, the BEP but not the BER rats demonstrated a
significant increase in CRF mRNA expression in the bed nucleus of the stria
terminalis (BNST) after stress. Hyporeactivity of the hypothalamic-pituitary
adrenal axis and the higher CRF expression in the BNST in BEP rats may contribute
to stress-induced binge-like sucrose eating in the BEP phenotype.
PMID- 27616711
TI - Optical and radiative properties of aerosols over Desalpar, a remote site in
western India: Source identification, modification processes and aerosol type
discrimination.
AB - Aerosol optical properties are analyzed for the first time over Desalpar (23.74
degrees N, 70.69 degrees E, 30m above mean sea level) a remote site in western
India during October 2014 to August 2015. Spectral aerosol optical depth (AOD)
measurements were performed using the CIMEL CE-318 automatic Sun/sky radiometer.
The annual-averaged AOD500 and Angstrom exponent (alpha440-870) values are found
to be 0.43+/-0.26 and 0.69+/-0.39, respectively. On the seasonal basis, high
AOD500 of 0.45+/-0.30 and 0.61+/-0.34 along with low alpha440-870 of 0.41+/-0.27
and 0.41+/-0.35 during spring (March-May) and summer (June-August), respectively,
suggest the dominance of coarse-mode aerosols, while significant contribution
from anthropogenic sources is observed in autumn (AOD500=0.47+/-0.26, alpha440
870=1.02+/-0.27). The volume size distribution and the spectral single-scattering
albedo also confirm the presence of coarse-mode aerosols during March-August. An
overall dominance of a mixed type of aerosols (~56%) mostly from October to
February is found via the AOD500 vs alpha440-870 relationship, while marine
aerosols contribute to ~18%. Spectral dependence of alpha and its second
derivative (alpha') are also used for studying the aerosol modification
processes. The average direct aerosol radiative forcing (DARF) computed via the
SBDART model is estimated to range from -27.08Wm-2 to -10.74Wm-2 at the top of
the atmosphere, from -52.21Wm-2 to -21.71Wm-2 at the surface and from 10.97Wm-2
to 26.54Wm-2 within the atmosphere. This atmospheric forcing translates into
heating rates of 0.31-0.75Kday-1. The aerosol properties and DARF are also
examined for different trajectory clusters in order to identify the sources and
to assess the influence of long-range transported aerosols over Desalpar.
PMID- 27616712
TI - Dual roles of AQDS as electron shuttles for microbes and dissolved organic matter
involved in arsenic and iron mobilization in the arsenic-rich sediment.
AB - Microbially-mediated arsenic (As) metabolism and iron (Fe) bioreduction from
sediments play crucial roles in global As/Fe cycle, and their mobilization is
associated with the various effects within the alliance of "mediator-bacteria-DOM
(Dissolved Organic Matter)". The gradient levels (0.05, 0.10 and 1.00mM) of
sodium anthraquinone-2,6-disulphonate (AQDS) as a mediator were investigated for
their impact on reductive dissolution of As(V) and Fe(III) from arsenic-rich
sediment. For the overall performance of AQDS-mediated reductive dissolution on
As(V) and Fe(III), a more positive effect resulting from 0.05mM AQDS was observed
compared to 0.10mM, whereas an inhibitory effect was observed with 1.00mM.
Compared to the biotic supplementation with acetate as electron donors,
approximately 13- and 6-fold increased levels of As(III) were released with 0.05
and 0.10mM, respectively, compared to 1.00mM AQDS (107.51MUg/L), and
approximately 4- and 3-fold increased Fe(II) levels (40.72mg/L) were observed
during the same conditions. Multiple-dynamic effects of "bacteria-AQDS-DOM",
which result from AQDS, shifted the microbial community and synchronously derived
terrestrial DOM, which potentially changes the DOM substrate and complex
formation of As(III)-Fe(II)-humic DOM. High-throughput sequencing results
indicated an increase in the abundance of metal-reducing bacteria (e.g., Bacillus
(>16%), Lactococcus (>13%), Pseudomonas (>4%) and Geobacter (>3%)) when
supplemented with 0.05 and 0.10mM of AQDS. However, a boost increasing the
abundance of metal oxidizing bacteria was observed with Alicyclobacillus (>16%),
Burkholderia (>7%), and Bradyrhizobium (>5%) upon supplementation with 1.00mM
AQDS. These novel insights have profound environmental implications and
significance in terms of engineering, not only for understanding the cycle of
As/Fe in sediment biochemical processes but for considering future alternative
bioremediation treatments.
PMID- 27616713
TI - Evaluation of eight high spatial resolution gridded precipitation products in
Adige Basin (Italy) at multiple temporal and spatial scales.
AB - This study provides a comprehensive evaluation of eight high spatial resolution
gridded precipitation products in Adige Basin located in Italy within 45-47.1
degrees N. The Adige Basin is characterized by a complex topography, and
independent ground data are available from a network of 101 rain gauges during
2000-2010. The eight products include the Version 7 TRMM (Tropical Rainfall
Measuring Mission) Multi-satellite Precipitation Analysis 3B42 product, three
products from CMORPH (the Climate Prediction Center MORPHing technique), i.e.,
CMORPH_RAW, CMORPH_CRT and CMORPH_BLD, PCDR (Precipitation Estimation from
Remotely Sensed Information using Artificial Neural Networks-Climate Data
Record), PGF (Global Meteorological Forcing Dataset for land surface modelling
developed by Princeton University), CHIRPS (Climate Hazards Group InfraRed
Precipitation with Station data) and GSMaP_MVK (Global Satellite Mapping of
Precipitation project Moving Vector with Kalman-filter product). All eight
products are evaluated against interpolated rain gauge data at the common 0.25
degrees spatial resolution, and additional evaluations at native finer spatial
resolution are conducted for CHIRPS (0.05 degrees ) and GSMaP_MVK (0.10 degrees
). Evaluation is performed at multiple temporal (daily, monthly and annual) and
spatial scales (grid and watershed). Evaluation results show that in terms of
overall statistical metrics the CHIRPS, TRMM and CMORPH_BLD comparably rank as
the top three best performing products, while the PGF performs worst. All eight
products underestimate and overestimate the occurrence frequency of daily
precipitation for some intensity ranges. All products tend to show higher error
in the winter months (December-February) when precipitation is low. Very slight
difference can be observed in the evaluation metrics and aspects between at the
aggregated 0.25 degrees spatial resolution and at the native finer resolutions
(0.05 degrees ) for CHIRPS and (0.10 degrees ) for GSMaP_MVK products. This study
has implications for precipitation product development and the global view of the
performance of various precipitation products, and provides valuable guidance
when choosing alternative precipitation data for local community.
PMID- 27616716
TI - The Effect of Storing Temperature and Duration on Urinary Hydration Markers.
AB - The purpose of this investigation was to quantify the effects of storage
temperature, duration, and the urinary sediment on urinary hydration markers.
Thirty-six human urine samples were analyzed fresh and then the remaining sample
was separated into 24 separate vials, six in each of the following four
temperatures: 22 degrees C, 7 degrees C, -20 degrees C, and -80 degrees C.
Two of each sample stored in any given temperature, were analyzed after 1, 2, and
7 days either following vortexing or centrifugation. Each urine sample was
analyzed for osmolality (UOsm), urine specific gravity (USG), and urine color
(UC). UOsm was stable at 22 degrees C, for 1 day (+5-9 mmol?kg-1, p > .05) and
at 7 degrees C, UOsm up to 7 days (+8-8 mmol?kg-1, p > .05). At -20 and -80
degrees C, UOsm decreased after 1, 2, and 7 days (9-61 mmol?kg-1, p < .05).
Vortexing the sample before analysis further decreased only UOsm in the -20
degrees C and -80 degrees C storage. USG remained stable up to 7 days when
samples were stored in 22 degrees C or 7 degrees C (p > .05) but declined
significantly when stored in -20 degrees C, and -80 degrees C (p < .001). UC
was not stable in any of the storing conditions for 1, 2, and 7 days. In
conclusion, these data indicate that urine specimens analyzed for UOsm or USG
remained stable in refrigerated (7 degrees C) environment for up to 7 days, and
in room temperature for 1 day. However, freezing (-20 and -80 degrees C) samples
significantly decreased the values of hydration markers.
PMID- 27616715
TI - Structural basis of cucumisin protease activity regulation by its propeptide.
AB - Cucumisin [EC 3.4.21.25], a subtilisin-like serine endopeptidase, was isolated
from melon fruit, Cucumis melo L. Mature cucumisin (67 kDa, 621 residues) is
produced by removal of the propeptide (10 kDa, 88 residues) from the cucumisin
precursor by subsequence processing. It is reported that cucumisin is inhibited
by its own propeptide. The crystal structure of mature cucumisin is reported to
be composed of three domains: the subtilisin-like catalytic domain, the protease
associated domain and the C-terminal fibronectin-III-like domain. In this study,
the crystal structure of the mature cucumisin*propeptide complex was determined
by the molecular replacement method and refined at 1.95 A resolution. In this
complex, the propeptide had a domain of the alpha-beta sandwich motif with four
stranded antiparallel beta-sheets, two helices and a strand of the C-terminal
region. The beta-sheets of the propeptide bind to two parallel surface helices of
cucumisin through hydrophobic interaction and 27 hydrogen bonds. The C-terminus
of the propeptide binds to the cleft of the active site as peptide substrates.
The inhibitory assay suggested that the C-terminal seven residues of the
propeptide do not inhibit the cucumisin activity. The crystal structure of the
cucumisin*propeptide complex revealed the regulation mechanism of cucumisin
activity.
PMID- 27616714
TI - Yap is essential for retinal progenitor cell cycle progression and RPE cell fate
acquisition in the developing mouse eye.
AB - Yap functions as a transcriptional regulator by acting together with sequence
specific DNA binding factors and transcription cofactors to mediate cell
proliferation in developing epithelial tissues and tumors. An upstream kinase
cascade controls nuclear localization and function in response to partially
identified exogenous signals, including cell-to-cell contact. Nevertheless, its
role in CNS development is poorly understood. In order to investigate Yap
function in developing CNS, we characterized the cellular outcomes after
selective Yap gene ablation in developing ocular tissues. When Yap was lost,
presumptive retinal pigment epithelium acquired anatomical and molecular
characteristics resembling those of the retinal epithelium rather than of RPE,
including loss of pigmentation, pseudostratified epithelial morphology and
ectopic induction of markers for retinal progenitor cells, like Chx10, and
neurons, like beta-Tubulin III. In addition, developing retina showed signs of
progressive degeneration, including laminar folding, thinning and cell loss,
which resulted from multiple defects in cell proliferation and survival, and in
junction integrity. Furthermore, Yap-deficient retinal progenitors displayed
decreased S-phase cells and altered cell cycle progression. Altogether, our
studies not only illustrate the canonical function of Yap in promoting the
proliferation of progenitors, but also shed new light on its evolutionarily
conserved, instructive role in regional specification, maintenance of junctional
integrity and precise regulation of cell proliferation during neuroepithelial
development.
PMID- 27616717
TI - Cognitive and affective processing of social exclusion in borderline personality
disorder and social anxiety disorder.
AB - Causal attributions of social events are crucial for understanding emotional
responses. Aim of the study was to identify appraisal processes in response to
social exclusion in borderline personality disorder (BPD) and social anxiety
disorder (SAD). Twenty-five patients with BPD, 25 patients with SAD and 25
healthy controls played Cyberball, a virtual ball-tossing paradigm that
experimentally induces social exclusion. Causal attributions, subjective feelings
and action tendencies in response to social exclusion were assessed. Both
clinical groups showed more internal attributions and less control attributions
than the control group, reported a higher increase in self-focused negative
emotions, along with more escape tendencies and less intent to engage in pleasant
activities. But only the BPD group reported higher hostile-intent attributions
and more aggressive action tendencies compared to healthy controls.
PMID- 27616718
TI - Anxiety and attention to threat: Cognitive mechanisms and treatment with
attention bias modification.
AB - Anxiety disorders are common and difficult to treat. Some cognitive models of
anxiety propose that attention bias to threat causes and maintains anxiety. This
view led to the development of a computer-delivered treatment: attention bias
modification (ABM) which predominantly trains attention avoidance of threat.
However, meta-analyses indicate disappointing effectiveness of ABM-threat
avoidance training in reducing anxiety. This article considers how ABM may be
improved, based on a review of key ideas from models of anxiety, attention and
cognitive control. These are combined into an integrative framework of cognitive
functions which support automatic threat evaluation/detection and goal-directed
thought and action, which reciprocally influence each other. It considers roles
of bottom-up and top-down processes involved in threat-evaluation, orienting and
inhibitory control in different manifestations of attention bias (initial
orienting, attention maintenance, threat avoidance, threat-distractor
interference) and different ABM methods (e.g., ABM-threat-avoidance, ABM-positive
search). The framework has implications for computer-delivered treatments for
anxiety. ABM methods which encourage active goal-focused attention-search for
positive/nonthreat information and flexible cognitive control across multiple
processes (particularly inhibitory control, which supports a positive goal
engagement mode over processing of minor threat cues) may prove more effective in
reducing anxiety than ABM-threat-avoidance training which targets a specific bias
in spatial orienting to threat.
PMID- 27616719
TI - Estimation of genetic variance in the age of genomics.
PMID- 27616720
TI - Panusin represents a new family of beta-defensin-like peptides in invertebrates.
AB - Beta_defensin have been solely found in vertebrates until beta-defensin-like
peptides were described as transcript isoforms in two species of Panulirus genus.
They were considered as putative antimicrobials since their biological activity
have not been demonstrated. Here we purified and characterized a defensin-like
peptide from the hemocytes of spiny lobster P. argus, hereafter named panusin.
Structurally, panusin presents a cysteine-stabilized alpha/beta motif, and is
prone to form homodimers. Biological activity of panusin showed broad-spectrum
antimicrobial activity, characterized for being strikingly salt-resistant.
Panusin did not showed hemolytic activity but was demonstrated its binding
capacity to different lipid membrane models, indicating amphipathicity of beta
sheet core as driving force for its antimicrobial activity. Panusin is considered
a new kind of arthropod defensin which share structural and biological features
with beta-defensin from vertebrates. The presence of beta-defensin like peptides
in crustacean might suggest the emergence of the evolutionary relationship of
beta-defensins from vertebrates.
PMID- 27616721
TI - Robotic and Open Radical Prostatectomy: The First Prospective Randomised
Controlled Trial Fuels Debate Rather than Closing the Question.
AB - Despite the finally acquired level 1 evidence, the urologic debate on open versus
robotic prostatectomy still persists. This trial from Brisbane will encourage
future studies that will better inform this debate and define what robotic
surgery offers.
PMID- 27616722
TI - Cryoablation for cT1b Renal Tumors? Yet To Be Determined.
PMID- 27616723
TI - The CAPRA Score at 10 Years: Contemporary Perspectives and Analysis of Supporting
Studies.
AB - : Tools that appraise oncologic risk are a critical component of research and
clinical management of prostate cancer (PCa). We performed a PubMed/Medline
search to review the concept, design, and clinical validation of the Cancer of
the Prostate Risk Assessment (CAPRA) score and similar systems in the
postsurgical (CAPRA-S) and primary androgen deprivation therapy (Japan CAPRA [J
CAPRA]) settings. We included reports addressing the CAPRA (n=13), CAPRA-S (n=4),
and J-CAPRA (n=5) scores. External validation studies for the CAPRA score have
yielded favorable clinical performance in both academic and community cohorts,
with concordance index (c-index) for biochemical recurrence (BCR) after
definitive treatment in the range of 0.66-0.81. Validation studies addressing the
postsurgical CAPRA-S score have demonstrated favorable prediction of distant end
points (c-index for BCR: 0.73-0.80; prostate cancer-specific mortality [PCSM]:
0.75-0.88). The J-CAPRA score was evaluated in 1378 men treated with primary ADT
and demonstrated excellent discrimination (c-index for progression-free survival:
0.80-0.89; PCSM: 0.820-0.836; overall survival: 0.665-0.700). The CAPRA score and
its derivatives have demonstrated robust clinical discrimination in a decade of
validation studies. The CAPRA score and similar multivariable stratification
systems are posed to replace prior older and less accurate risk group categories.
PATIENT SUMMARY: We addressed the development of the Cancer of the Prostate Risk
Assessment (CAPRA) score, its methodology, and its supporting studies. The CAPRA
score and similarly designed tools have yielded strong performance in the
prediction of numerous prostate cancer end points.
PMID- 27616724
TI - Prevalence of dental erosion among people with gastroesophageal reflux disease in
China.
AB - STATEMENT OF PROBLEM: Gastroesophageal reflux disease (GERD) is typically
diagnosed based on symptoms of regurgitation and heartburn, although it may also
manifest as asthma-like symptoms, laryngitis, or dental erosion. PURPOSE: The
purpose of this prospective, cross-sectional study was to assess the prevalence
of dental erosion in people with GERD and to evaluate the association between
GERD and dental erosion. MATERIAL AND METHODS: The presence, severity, and
pattern of dental erosion was assessed in 51 participants with GERD and 50
participants without GERD using the Smith and Knight tooth wear index. Medical,
dietary, and dental histories were collected by questionnaire. Factors
potentially related to dental erosion, including GERD, were evaluated by logistic
regression. RESULTS: Dental erosion was observed in 31 (60.8%) participants with
GERD and 14 (28%) participants without GERD. Bivariate analysis revealed that
participants with GERD were more likely to experience dental erosion (crude odds
ratio [cOR]: 2.74; 95% CI: 1.19, 6.32) than participants without GERD.
Multivariate analysis also revealed that participants with GERD had a higher risk
of dental erosion (adjusted odds ratio [aOR]: 3.97; 95% CI: 1.45, 10.89).
Consumption of grains and legumes, the most frequently consumed foods in China,
did not correlate with dental erosion. However, carbonated beverage consumption
was significantly associated with GERD and dental erosion (aOR: 3.34; 95% CI:
1.01, 11.04; P=.04). CONCLUSIONS: GERD was positively correlated with dental
erosion. Carbonated beverage consumption can increase the risk of both GERD and
dental erosion.
PMID- 27616725
TI - Cervical Lymph Node Metastases After Thyroidectomy for Papillary Thyroid
Carcinoma Usually Remain Stable for Years.
AB - BACKGROUND: Lymph node (LN) recurrence detected by ultrasound (US) is a very
common problem after initial treatment for papillary thyroid carcinoma (PTC).
Most patients with PTC have an excellent disease-specific survival even with LN
recurrence. Recently, watchful waiting with serial cervical US evaluations would
be considered a reasonable approach to management of LN recurrence in selected
patients. On the other hand, some patients with LN recurrence have demonstrated
clinically significant disease progression during follow-up. The objective of the
present study was to document the changes of cervical LN metastases after initial
treatment and identify useful information for deciding how best to manage
individual patients with LN recurrence. METHODS: This retrospective review
identified 83 consecutive PTC patients with at least one LN on the postoperative
US diagnosed with fine needle aspiration biopsy or the thyroglobulin titer in the
wash-out of the needle. The change in LN size was determined using serial US
studies over time. RESULTS: The subjects were 15 men and 68 women, with a median
age at initial surgery of 50.6 years (range, 18-80 years). The median LN size at
the start of the observation period was 1.3 cm (range, 0.5-2.4 cm) in the largest
diameter. After a median follow-up of 7.2 years, the median growth rate of the
nodes showing structural progression was 1.4 mm per year (range, 0-12.0 mm/year).
Seventeen of 83 patients (20.5%) demonstrated an increase in LN size of at least
3 mm, only 8.4% (7 of 83) had an increase of at least 5 mm, and 39.7% (33 of 83)
resolved. Distant metastases were present in 11 of 83 patients. Ten-year and
fifteen-year disease-specific survival rates after diagnosis of LN recurrence
were 84.7% and 72.6%, respectively. Older age and recurrent LN growth of more
than 3 mm/year were recognized as independent predictors for short survival on
both univariate and multivariate analyses (p < 0.05). CONCLUSIONS: Most lymph
node recurrences may remain stable for a long time and not be immediately life
threatening. However, recurrent LN growth of more than 3 mm per year could be
related to mortality.
PMID- 27616727
TI - Why and how did Israel adopt activity-based hospital payment? The Procedure
Related Group incremental reform.
AB - Historically, Israel paid its non-profit hospitals on a perdiem (PD) basis.
Recently, like other OECD countries, Israel has moved to activity-based payments.
While most countries have adopted a diagnostic related group (DRG) payment
system, Israel has chosen a Procedure-Related Group (PRG) system. This differs
from the DRG system because it classifies patients by procedure rather than
diagnosis. In Israel, the PRG system was found to be more feasible given the lack
of data and information needed in the DRG classification system. The Ministry of
Health (MoH) chose a payment scheme that depends only on inhouse creation of PRG
codes and costing, thus avoiding dependence on hospital data. The PRG tariffs are
priced by a joint Health and Finance Ministry commission and updated
periodically. Moreover, PRGs are believed to achieve the same main efficiency
objectives as DRGs: increasing the volume of activity, shortening unnecessary
hospitalization days, and reducing the gaps between the costs and prices of
activities. The PRG system is being adopted through an incremental reform that
started in 2002 and was accelerated in 2010. The Israeli MoH involved the main
players in the hospital market in the consolidation of this potentially
controversial reform in order to avoid opposition. The reform was implemented
incrementally in order to preserve the balance of resource allocation and overall
expenditures of the system, thus becoming budget neutral. Yet, as long as gaps
remain between marginal costs and prices of procedures, PRGs will not attain all
their objectives. Moreover, it is still crucial to refine PRG rates to reflect
the severity of cases, in order to tackle incentives for selection of patients
within each procedure.
PMID- 27616728
TI - Neuroendocrine factors distinguish juvenile psychopathy variants.
AB - The characteristic pattern of emotional hypo-reactivity observed in primary
psychopathy is not evident in secondary psychopathy, which is thought to
originate from childhood adversity and co-occurring anxiety. The main aim of this
study was to test whether salivary afternoon cortisol, Dehydroepiandrosterone
(DHEA), and cortisol-to-DHEA concentrations, which at high levels indicate risk
for chronic stress and poor mental health, distinguished secondary from primary
variants of callous-unemotional (CU) traits-the affective component of
psychopathy. This aim was achieved by first identifying psychopathy variants
using latent profile analysis of CU, anxiety, and aggression scores among 232
incarcerated adolescent boys (M age = 16.75). Based on a subset with
neuroendocrine data (n = 201), aggressive secondary CU variants had lower
afternoon DHEA concentrations and higher cortisol-to-DHEA ratios and comorbid
psychopathology compared with all other groups. In contrast, two primary CU
variants (aggressive and non-aggressive types) emerged with profiles
characterized by low to average psychopathology and high DHEA levels. Findings
contribute to a growing literature base suggesting that biomarkers may
distinguish youth on separable developmental pathways to psychopathy.
PMID- 27616726
TI - The mismatch negativity as an index of cognitive decline for the early detection
of Alzheimer's disease.
AB - Evidence suggests that Alzheimer's disease (AD) is part of a continuum,
characterized by long preclinical phases before the onset of clinical symptoms.
In several cases, this continuum starts with a syndrome, defined as mild
cognitive impairment (MCI), in which daily activities are preserved despite the
presence of cognitive decline. The possibility of having a reliable and sensitive
neurophysiological marker that can be used for early detection of AD is extremely
valuable because of the incidence of this type of dementia. In this study, we
aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a
marker of cognitive decline from normal ageing progressing from MCI to AD. We
compared aMMN elicited in the frontal and temporal locations by duration deviant
sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three
groups. We found that at a short ITI, MCI showed only the temporal component of
aMMN and AD the frontal component compared to healthy elderly who presented both.
At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal
locations. Our study provides empirical evidence for the possibility to adopt
aMMN as an index for assessing cognitive decline in pathological ageing.
PMID- 27616729
TI - Dedicated C-fibre viscerosensory pathways to central nucleus of the amygdala.
AB - KEY POINTS: Emotions are accompanied by concordant changes in visceral function,
including cardiac output, respiration and digestion. One major forebrain
integrator of emotional responses, the amygdala, is considered to rely on
embedded visceral afferent information, although few details are known. In the
present study, we retrogradely transported dye from the central nucleus of the
amygdala (CeA) to identify CeA-projecting nucleus of the solitary tract (NTS)
neurons for synaptic characterization and compared them with unlabelled, near
neighboor NTS neurons. Solitary tract (ST) afferents converged onto NTS-CeA
second-order sensory neurons in greater numbers, as well as indirectly via
polysynaptic pathways. Unexpectedly, all mono- and polysynaptic ST afferent
pathways to NTS-CeA neurons were organized exclusively as either transient
receptor potential cation channel subfamily V member 1 (TRPV1)-sensitive or TRPV1
resistant, regardless of whether intervening neurons were excitatory or
inhibitory. This strict sorting provides viscerosensory signals to CeA about
visceral conditions with respect to being either 'normal' via A-fibres or 'alarm'
via TRPV1 expressing C-fibres and, accordingly, this pathway organization
probably encodes interoceptive status. ABSTRACT: Emotional state is impacted by
changes in visceral function, including blood pressure, breathing and digestion.
A main line of viscerosensory information processing occurs first in the nucleus
of the solitary tract (NTS). In the present study conducted in rats, we examined
the synaptic characteristics of visceral afferent pathways to the central nucleus
of the amygdala (CeA) in brainstem slices by recording from retrogradely labelled
NTS projection neurons. We simultaneously recorded neuron pairs: one dye positive
(i.e. NTS-CeA) and a second unlabelled neighbour. Graded shocks to the solitary
tract (ST) always (93%) triggered EPSCs at CeA projecting NTS neurons. Half of
the NTS-CeA neurons received at least one primary afferent input (classed 'second
order') indicating that viscerosensory information arrives at the CeA conveyed
via a pathway involving as few as two synapses. The remaining NTS-CeA neurons
received viscerosensory input only via polysynaptic pathways. By contrast, ~3/4
of unlabelled neighbouring neurons were directly connected to ST. NTS-CeA neurons
received greater numbers of ST-related inputs compared to unlabelled NTS neurons,
indicating that highly convergent viscerosensory signals reach the CeA.
Remarkably, despite multifibre convergence, all single NTS-CeA neurons received
inputs derived from only unmyelinated afferents [transient receptor potential
cation channel subfamily V member 1 (TRPV1) expressing C-fibres] or only non
TRPV1 ST afferent inputs, and never a combination of both. Such segregation means
that visceral afferent information followed separate lines to reach the CeA.
Their very different physiological activation profiles mean that these parallel
visceral afferent pathways encode viscerosensory signals to the amygdala that may
provide interoceptive assessments to impact on behaviours.
PMID- 27616730
TI - Topical Treatment of Leishmania tropica Infection Using (-)-alpha-Bisabolol
Ointment in a Hamster Model: Effectiveness and Safety Assessment.
AB - There is currently no reliable treatment for the management of cutaneous
leishmaniasis, and intralesional antimonial injections remain the main treatment.
The present work aims at evaluating the antileishmanial effectiveness and safety
of (-)-alpha-bisabolol (1) in a novel topical formulation on a cutaneous
leishmaniasis model involving Leishmania tropica-infected Syrian hamsters. The
topical treatment with 1 reduced lesion thickness to 56% at 2.5%, showing a
higher efficacy than the reference control, meglumine antimoniate. Other regimens
(ointment at 1% and 5% and oral treatment at 200 mg/kg) reduced the footpad
thickness as well. The skin parasite load decreased after the experiment in all
treatment groups, particularly in those animals treated with the 2.5% formulation
(83.2%). Treatment with (-)-alpha-bisabolol at different concentrations or
through an oral route did not lead to the appearance of toxicity or side effects
in healthy hamsters or infected animals. Therefore, topical (-)-alpha-bisabolol
was more effective than meglumine antimoniate in this cutaneous leishmaniasis
model without showing toxicity effects on the hamsters. These results are of
great interest and might be used for the development of alternatives for the
treatment of cutaneous leishmaniasis, either in monotherapy or in combination
with other drugs whose skin permeability could be enhanced by this sesquiterpene.
PMID- 27616731
TI - Collection of daily patient reported outcomes is feasible and demonstrates
differential patient experience in chronic kidney disease.
AB - INTRODUCTION: Patient reported outcomes (PROs) are a critical metric documenting
the impact of disease and treatment from the patient's perspective. A variety of
generic and disease specific PRO measures (PROMs) are used in chronic kidney
disease (CKD) but studies are primarily cross-sectional. None of the available
PROMs are designed for frequent iterative application. METHODS: An online PROM
for daily use in dialysis and CKD 4/5 patients was developed. The custom website
utilised visual analogue scales to capture 6 PROs (general well being (GWB),
pain, sleep, breathing, energy, and appetite). Outcomes of interest were uptake,
response rates, intermodality variation, and change in PRO corresponding to
predefined events. FINDINGS: Forty-three patients submitted at least once and 34
submitted beyond 30 days. Median follow-up was 247 days, 64% male, age 62 +/- 12
years. In individuals submitting for >30 days, dialysis patients had
significantly worse median scores compared to CKD for sleep (47[32-80], 97[76
99], P = 0.003), appetite (66[50-96], 97[88-100], P = 0.008), energy (47[40-89],
84[67-96], P = 0.031), and GWB (63[49-94], 93[71-98], P = 0.026). Patients
demonstrated a variety of stable bandwidths of response, deviations from this
were associated with specific events e.g., acute admission, vascular procedures,
disturbed fluid status, and dialysis start. DISCUSSION: We successfully
introduced an online, patient acceptable, iterative PROM that discriminates
symptom burden, cross-sectionally, and longitudinally. Further work will
prospectively examine the predictive power of changes in PRO and more rigorously
investigate the potential use of these methods to optimise patient care.
PMID- 27616732
TI - No Dose Response Effect of Carbohydrate Mouth Rinse on Cycling Time-Trial
Performance.
AB - The aim of the current study was to investigate the influence of mouth rinsing
carbohydrate at increasing concentrations on ~1 hr cycle time trial performance.
Eleven male cyclists completed three experimental trials, following an overnight
fast. Cyclists performed a ~1 hr time trial on a cycle ergometer, while rinsing
their mouth for 5 s with either a 7% maltodextrin solution (CHO), 14% CHO or a
taste-matched placebo (PLA) after every 12.5% of the set amount of work. Heart
rate was recorded every 12.5% of the time trial, while RPE and GI comfort were
determined every 25% of the time trial. The mouth rinse protocol influenced the
time to complete the time trial (p < .001), with cyclists completing the time
trial faster during 7% CHO (57.3 +/- 4.5 min; p = .004) and 14% CHO (57.4 +/- 4.1
min; p = .007), compared with PLA (59.5 +/- 4.9 min). There was no difference
between the two carbohydrate trials (p = .737). There was a main effect of time
(P<0.001) for both heart rate and RPE, but no main effect of trial (p = .107 and
p = .849, respectively). Scores for GI comfort ranged from 0-2 during trials,
indicating very little GI discomfort during exercise. In conclusion, mouth
rinsing and expectorating a 7% maltodextrin solution, for 5 s routinely during
exercise was associated with improved cycle time trial performance approximately
1 h in duration. Increasing the carbohydrate concentration of the rinsed solution
from 7% to 14% resulted in no further performance improvement.
PMID- 27616733
TI - Animal serial killing: The first criminal conviction for animal cruelty in
Brazil.
AB - Animal cruelty is a known behavior of psychopaths, and although the serial
killing of humans is widely acknowledged worldwide, this type of crime against
animals is seldom discussed. This report describes the necropsy and toxicological
findings of 37 dogs and cats, which were found dead in plastic bags in Sao Paulo,
Brazil. The animals had all been in the care of an alleged animal rescuer and
were to be referred for adoption before being found dead. In the necropsy, the
animals showed varying degrees of putrefaction, indicating different periods of
death, as well as single or multiple perforations on the thorax. The perforations
reached the heart, lungs or large thoracic vessels, culminating in
hemopericardium and hemothorax that led to death by circulatory failure and
cardiac tamponade. Blood from the heart and thoracic cavity was analyzed by gas
chromatography coupled with mass spectrometry (GC-MS) and tested positive for
ketamine, a dissociative anesthetic. The suspect declared that she had killed
only five of the animals and that they had all been fatally sick. The necropsy
proved that all 37 animals were killed in the same way, that none of the animals
had any terminal diseases and that a restricted drug was used. The suspect was
sentenced to 12 years, 6 months and 14days of prison for the killing of the 37
animals. This was the first conviction for the crime of animal cruelty in Brazil.
The combined role of police, forensic veterinary pathologists and prosecutors
were essential to the conviction, which was a great historical occasion in the
fight against animal cruelty.
PMID- 27616734
TI - Water, sanitation and hygiene related risk factors for soil-transmitted helminth
and Giardia duodenalis infections in rural communities in Timor-Leste.
AB - There is little evidence on prevalence or risk factors for soil transmitted
helminth infections in Timor-Leste. This study describes the epidemiology, water,
sanitation and hygiene, and socioeconomic risk factors of STH and intestinal
protozoa amongst communities in Manufahi District, Timor-Leste. As part of a
cluster randomised controlled trial, a baseline cross-sectional survey was
conducted across 18 villages, with data from six additional villages. Stool
samples were assessed for soil transmitted helminth and protozoal infections
using quantitative PCR (qPCR) and questionnaires administered to collect water,
sanitation and hygiene and socioeconomic data. Risk factors for infection were
assessed using multivariable mixed-effects logistic regression, stratified by age
group (preschool, school-aged and adult). Overall, soil transmitted helminth
prevalence was 69% (95% Confidence Interval 67-71%), with Necator americanus
being most common (60%; 95% Confidence Interval 58-62%) followed by Ascaris spp.
(24%; 95% Confidence Interval 23-26%). Ascaris-N. americanus co-infection was
common (17%; 95% Confidence Interval 15%-18%). Giardia duodenalis was the main
protozoan identified (13%; 95% Confidence Interval 11-14%). Baseline water,
sanitation and hygiene infrastructure and behaviours were poor. Although risk
factors varied by age of participants and parasite species, risk factors for N.
americanus infection included, generally, age in years, male sex, and
socioeconomic quintile. Risk factors for Ascaris included age in years for
children, and piped water to the yard for adults. In this first known assessment
of community-based prevalence and associated risk factors in Timor-Leste, soil
transmitted helminth infections were highly prevalent, indicating a need for soil
transmitted helminth control. Few associations with water, sanitation and hygiene
were evident, despite water, sanitation and hygiene being generally poor. In our
water, sanitation and hygiene we will investigate implications of improving WASH
on soil transmitted helminth infection in impoverished communities.
PMID- 27616735
TI - Estimation of Serum YKL-40 by Real-Time Surface Plasmon Resonance Technology in
North-Indian Asthma Patients.
AB - BACKGROUND: Many studies reported for estimating serum YKL-40 using ELISA or RIA
methods. This study introduces the plausible utilization of real-time surface
plasmon resonance (SPR) technology in investigating the expression of serum YKL
40 protein levels and ELISA method for serum IgE in bronchial asthma. METHODS: A
commercially available BIAcore 2000 instrument, based on SPR technology, was
utilized for assessing serum YKL-40 levels in a control sample size of 45 and
active sample size of 97. Antibody immobilization was optimized to obtain the
best sensor performance and a sensitive analytic detection. A commercially
available ELISA kit was utilized for detecting serum IgE to estimate allergic
condition-associated asthma. RESULTS: The results of SPR technology could
distinctly classify with highly statistical significance, the asthma severities
by estimating the elevated levels of YKL-40 in blood sera of minute quantities
(up to 0.33 ng/ml), and thus differentiates superior utility in comparison with
ELISA method. No statistically significant correlation of YKL-40 and IgE was
observed. CONCLUSIONS: Serum YKL-40 may be used as a protein marker in
classifying asthma severity by applying SPR technology as a reliable, label-free,
highly sensitive, and cost-effective tool.
PMID- 27616737
TI - Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed
with a high-fat/cholesterol diet.
AB - BACKGROUND: Leucine supplementation has been reported to improve lipid
metabolism. However, lipid metabolism in adipose tissues and liver has not been
extensively studied for leucine supplementation in mice fed with a high
fat/cholesterol diet (HFCD). DESIGN: C57BL/6J mice were fed a chow diet, HFCD,
HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3%
Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total
cholesterol (TC), triglyceride in serum and liver, and serum adipokines were
analyzed. In addition, expression levels of proteins associated with hepatic
lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were
determined. RESULTS: Mice in the HFCD group developed obesity and deteriorated
lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain
and TC levels in circulation and the liver without changing energy intake. The
decrease in body fat was supported by histological examination in the WAT and
liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin,
IL-6, and tumor necrosis factor-alpha, were significantly decreased by
supplemented leucine. At the protein level, leucine potently decreased the
hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase)
and corresponding upstream proteins. In epididymal WAT, the reduced expression
levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive
lipase and adipose triglyceride lipase, were reversed when leucine was
supplemented. Uncoupling protein 1, beta3 adrenergic receptors, peroxisome
proliferator-activated receptor g coactivator-1alpha, and fibroblast growth
factor 21 were involved in the thermogenic program and WAT browning. Leucine
additionally upregulated their protein expression in both WAT and interscapular
brown adipose tissue. CONCLUSION: This study demonstrated that chronic leucine
supplementation reduced the body weight and improved the lipid profile of mice
fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis,
adipocyte lipolysis, and WAT browning.
PMID- 27616736
TI - VAMP2 is implicated in the secretion of antibodies by human plasma cells and can
be replaced by other synaptobrevins.
AB - The production and secretion of antibodies by human plasma cells (PCs) are two
essential processes of humoral immunity. The secretion process relies on a group
of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein
receptors (SNAREs), which are located in the plasma membrane (t-SNAREs) and in
the antibody-carrying vesicle membrane (v-SNARE), and mediate the fusion of both
membranes. We have previously shown that SNAP23 and STX4 are the t-SNAREs
responsible for antibody secretion. Here, using human PCs and antibody-secreting
cell lines, we studied and characterized the expression and subcellular
distribution of vesicle associated membrane protein (VAMP) isoforms,
demonstrating that all isoforms (with the exception of VAMP1) are expressed by
the referenced cells. Furthermore, the functional role in antibody secretion of
each expressed VAMP isoform was tested using siRNA. Our results show that VAMP2
may be the v-SNARE involved in vesicular antibody release. To further support
this conclusion, we used tetanus toxin light chain to cleave VAMP2, conducted
experiments to verify co-localization of VAMP2 in antibody-carrying vesicles, and
demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in
situ interaction of VAMP2 with STX4. Taken together, these findings implicate
VAMP2 as the main VAMP isoform functionally involved in antibody secretion.
PMID- 27616738
TI - Effects of spinach nitrate on insulin resistance, endothelial dysfunction markers
and inflammation in mice with high-fat and high-fructose consumption.
AB - BACKGROUND: Insulin resistance, which is associated with an increased risk of
cardiovascular morbidity and mortality, has become a leading nutrition problem.
Inorganic nitrate enriched in spinach has been demonstrated to reverse the
pathological features of insulin resistance and endothelial dysfunction. However,
the effects of a direct intake of nitrate-enriched spinach on insulin resistance
and endothelial dysfunction have not been studied. OBJECTIVE: To investigate the
effects of spinach nitrate on insulin resistance, lipid metabolism, endothelial
function, and inflammation in mice fed with a high-fat and high-fructose diet.
DESIGN: A diet intervention of spinach with or without nitrate was performed in
mice. A high-fat and high-fructose diet was used to cause insulin resistance,
endothelial dysfunction, and inflammation in mice. The impacts of spinach nitrate
on lipid profile, insulin resistance, markers of endothelial function, and
inflammation were determined in mice. RESULTS: Spinach nitrate improved the
vascular endothelial function of the mice with high-fat and high-fructose
consumption, as evidenced by the elevated plasma nitrite level, increased serum
nitric oxide (NO) level and decreased serum ET-1 level after spinach nitrate
intervention. Spinach nitrate also reduced serum triglycerides, total
cholesterol, and low-density lipoprotein-cholesterol levels and elevated serum
high-density lipoprotein-cholesterol levels in the mice fed with a high-fat and
high-fructose diet. Mice receiving spinach with 60 mg/kg of nitrate (1.02+/-0.34)
showed a significantly low homeostasis model assessment-insulin resistance index
as compared with the model mice (2.05+/-0.58), which is indicating that spinach
nitrate could effectively improve the insulin resistance. In addition, spinach
nitrate remarkably decreased the elevated serum C-reactive protein, tumor
necrosis factor alpha, and interleukin-6 levels induced by a high-fat and high
fructose diet. CONCLUSIONS: The intake of spinach nitrate can augment NO status,
improve lipid homeostasis, relieve inflammation, and enhance endothelial
function, suggesting that spinach is promising dietary supplements for insulin
resistance prevention.
PMID- 27616739
TI - Unpacking the therapist effect: Impact of treatment length differs for high- and
low-performing therapists.
AB - OBJECTIVE: Differences between therapists in their average outcomes (i.e.,
therapist effects) have become a topic of increasing interest in psychotherapy
research in the past decade. Relatively little work, however, has moved beyond
identifying the presence of significant between-therapist variability in patient
outcomes. The current study sought to examine the ways in which therapist effects
emerge over the course of time in psychotherapy. METHOD: We used a large
psychotherapy data set (n = 5828 patients seen by n = 158 therapists for 50,048
sessions of psychotherapy) and examined whether outcomes diverge for high
performing (HP) and low-performing (LP) therapists as treatment duration
increases. RESULTS: Therapists accounted for a small but significant proportion
of variance in patient outcomes that was not explained by differences between
therapists' caseload characteristics. The discrepancy in outcomes between HP and
LP therapists increased as treatment duration increased (interaction coefficient
= 0.071, p < .001). In addition, patients' trajectories of change were a function
of their therapist's average outcome as well as the patient's duration of
treatment (interaction coefficient = 0.060, p = .040). CONCLUSIONS: Indeed,
patterns of change previously described ignoring between-therapist differences
(e.g., dose-effect, good-enough level model) may vary systematically when
disaggregated by therapist effect.
PMID- 27616742
TI - Correction of neonatal stifle luxation in a 35-day-old cockatiel (Nymphicus
hollandicus).
PMID- 27616741
TI - Fyn deficiency attenuates renal fibrosis by inhibition of phospho-STAT3.
AB - The hallmark of renal tubulointerstitial fibrosis is the accumulation of
myofibroblasts and extracellular matrix proteins. Fyn, a member of the Src family
of kinases, has diverse biological functions including regulation of mitogenic
signaling and proliferation and integrin-mediated interaction. Src family
proteins promote pulmonary fibrosis by augmenting transforming growth factor-beta
signaling, but their role in renal fibrosis is less understood. We observed
upregulation of Fyn in a renal fibrosis model induced by unilateral ureteral
obstruction. Upon ureteral obstruction, Fyn-deficient mice exhibited attenuated
renal fibrosis relative to wild-type mice. Furthermore, obstruction-induced renal
expression of type I collagen, fibronectin, alpha-smooth muscle actin, and
plasminogen activator inhibitor-1 was suppressed. Pharmacologic inhibition of Fyn
blocked induction of extracellular matrix proteins in kidney cell lines.
Importantly, the attenuation of renal fibrosis by Fyn deficiency was not
accompanied by changes in the Smad pathway. Rather, the antifibrotic effect of
Fyn deficiency was associated with downregulation of signal transducer and
activator of transcription 3 (STAT3). Small, interfering RNA targeting STAT3 in
Fyn-deficient cells further suppressed alpha-smooth muscle actin expression,
whereas a STAT3 activator partially restored plasminogen activator inhibitor-1
expression, indicating that STAT3 signaling is critically involved in this
process. Thus, Fyn plays an important role in renal fibrosis. Hence, Fyn kinase
inhibitors may be therapeutically useful against renal fibrosis.
PMID- 27616743
TI - Synthesis, Identification, and Structure Elucidation of Adducts Formed by
Reactions of Hydroxycinnamic Acids with Glutathione or Cysteinylglycine.
AB - Grape polyphenols, especially hydroxycinnamic acids such as caftaric and caffeic
acid, are prone to enzymatic oxidation reactions during the winemaking process,
forming o-quinones and leading to color darkening. Glutathione is capable of
trapping these o-quinones and thus limiting juice browning. In this study, the
addition of glutathione or cysteinylglycine onto caftaric or caffeic acid o
quinones formed by polyphenoloxidase-catalyzed reactions was investigated by UPLC
DAD-ESIMS and NMR data analyses. Complete identification of adducts has been
achieved via NMR data. The results confirmed that the favored reaction is the
substitution of the sulfanyl group of cysteine at C-2 of the aromatic ring.
Several minor isomers, namely, the cis-isomer of the 2-S adduct and trans-isomers
of the 5-S and 6-S adducts, and the 2,5-di-S-glutathionyl adducts were also
identified and quantified by qNMR. With the exception of 2-(S-glutathionyl)- and
2,5-di(S-glutathionyl)-trans-caftaric acid, these products had never been
formally identified. In particular, the 5-S and 6-S derivatives are reported here
for the first time. The first formal identification of 2-S cis-derivatives is
also provided. Moreover, NMR and UPLC-DAD-ESIMS analysis showed that signature UV
and MS spectra can serve as markers of the conformation and substitution position
in the aromatic ring for each of the isomers.
PMID- 27616740
TI - The infectious particle of insect-borne totivirus-like Omono River virus has
raised ridges and lacks fibre complexes.
AB - Omono River virus (OmRV) is a double-stranded RNA virus isolated from Culex
mosquitos, and it belongs to a group of unassigned insect viruses that appear to
be related to Totiviridae. This paper describes electron cryo-microscopy (cryoEM)
structures for the intact OmRV virion to 8.9 A resolution and the structure of
the empty virus-like-particle, that lacks RNA, to 8.3 A resolution. The
icosahedral capsid contains 120-subunits and resembles another closely related
arthropod-borne totivirus-like virus, the infectious myonecrosis virus (IMNV)
from shrimps. Both viruses have an elevated plateau around their icosahedral 5
fold axes, surrounded by a deep canyon. Sequence and structural analysis suggests
that this plateau region is mainly composed of the extended C-terminal region of
the capsid proteins. In contrast to IMNV, the infectious form of OmRV lacks
extensive fibre complexes at its 5-fold axes as directly confirmed by a contrast
enhancement technique, using Zernike phase-contrast cryo-EM. Instead, these fibre
complexes are replaced by a short "plug" structure at the five-fold axes of OmRV.
OmRV and IMNV have acquired an extracellular phase, and the structures at the
five-fold axes may be significant in adaptation to cell-to-cell transmission in
metazoan hosts.
PMID- 27616744
TI - Utility of 18 F-FDG PET/CT scan to diagnose the etiology of fever of unknown
origin in patients on dialysis.
AB - INTRODUCTION: Studies on fever of unknown origin (FUO) in patients of chronic
kidney disease and end stage renal disease patients on dialysis were not many. In
this study, we used 18 F-FDG PET/CT scan whole body survey for detection of
hidden infection, in patients on dialysis, labelled as FUO. METHODS: In this
retrospective study, 20 patients of end stage renal disease on dialysis were
investigated for the cause of FUO using 18F-FDG PET/CT scan. All these patients
satisfied the definition of FUO as defined by Petersdorf and Beeson. Any focal
abnormal site of increased FDG concentration detected by PET/CT, either a
solitary or multiple lesions was documented and at least one of the detected
abnormal sites of radio tracer concentration was further examined for
histopathology. FINDINGS: All patients were on renal replacement therapy. Of
these, 18 were on hemodialysis and two were on peritoneal dialysis. 18F-FDG
PET/CT scan showed metabolically active lesions in 15 patients and metabolically
quiescent in five patients. After 18F-FDG PET/CT scan all, but one patient had a
change in treatment for fever. Anti-tuberculous treatment was given in 15
patients, antibiotics in four patients and anti-malaria treatment in one patient.
DISCUSSION: The present study is first study of 18F-FDG PET/CT scan in patients
of end stage renal disease on dialysis with FUO. The study showed that the 18 F
FDG PET/CT scan may present an opportunity to attain the diagnosis in end stage
renal disease patients on dialysis with FUO.
PMID- 27616745
TI - No Effect of Acute and 6-Day Nitrate Supplementation on VO2 and Time-Trial
Performance in Highly Trained Cyclists.
AB - While the majority of studies reporting ergogenic effects of dietary nitrate have
used a multiday supplementation protocol, some studies suggest that a single dose
of dietary nitrate before exercise can also improve subsequent performance. We
aimed to compare the impact of acute and 6-day sodium nitrate supplementation on
oxygen uptake (VO2) and time-trial performance in trained cyclists. Using a
randomized, double-blind, cross-over design, 17 male cyclists (25 +/- 4 y,
VO2peak 65 +/- 4 ml.kg-1.min-1, Wmax 411 +/- 35 W) were subjected to 3 different
trials; 5 days placebo and 1 day sodium nitrate supplementation (1-DAY); 6 days
sodium nitrate supplementation (6-DAY); 6 days placebo supplementation (PLA).
Nitrate was administered as 1097 mg sodium nitrate providing 800 mg (~12.9 mmol)
nitrate per day. Three hours after ingestion of the last supplemental bolus,
indirect calorimetry was performed while subjects performed 30 min of exercise at
45% Wmax and 30 min at 65% Wmax on a cycle ergometer, followed by a 10 km time
trial. Immediately before exercise, plasma [nitrate] and [nitrite] increased to a
similar extent during the 6-DAY and 1-DAY trial, but not with PLA (plasma
nitrite: 501 +/- 205, 553 +/- 278, and 239 +/- 74 nM, respectively; p < .001). No
differences were observed between interventions in VO2 during submaximal
exercise, or in time to complete the time-trial (6-DAY: 1004 ?+/- 61, 1-DAY: 1022
+/- 72, PLA: 1017 +/- 71 s; p = .28). We conclude that both acute and 6-days of
sodium nitrate supplementation do not alter VO2 during submaximal exercise or
improve time-trial performance in highly trained cyclists, despite increasing
plasma [nitrate] and [nitrite].
PMID- 27616746
TI - Staging and classification criteria for middle ear cholesteatoma proposed by the
Japan Otological Society.
AB - In order to provide a basis for meaningful exchange of information among those
treating cholesteatoma, the Committee on Nomenclature of the Japan Otological
Society (JOS) was appointed in 2004 to create a cholesteatoma staging system as
simple as possible to use in clinical practice in Japan. Following the
announcement of preliminary criteria for the staging of pars flaccida (attic)
cholesteatoma in 2008, we proposed the 2010 JOS staging system for two major
types of retraction pocket cholesteatoma, pars flaccida and pars tensa
cholesteatoma. Since then, the JOS staging system has been widely used in
clinical studies of cholesteatoma in Japan, allowing standardization in reporting
of surgical outcomes based on the respective stages of cholesteatoma. We have
recently expanded the range of cholesteatoma by adding cholesteatoma secondary to
a tensa perforation and congenital cholesteatoma as the 2015 JOS staging system
for middle ear cholesteatoma. Although further revisions may be required for
universal acceptance of these criteria, we hope our staging system will open the
way for international consensus on staging and classification of middle ear
cholesteatoma in the near future.
PMID- 27616747
TI - Free-flap reconstruction for the management of life-threatening hereditary
hemorrhagic telangiectasia.
AB - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multi
systemic disease that exhibits increasing penetrance with age. Some patients
present with severe life-threatening epistaxis which is intractable to all common
treatment modalities. A 63-year-old female patient with hereditary hemorrhagic
telangiectasia (HHT) presented with recurrent life-threatening epistaxis that
required repeated transfusions despite multiple embolizations and
septodermoplasty. Previous septodermoplasty failed due to septal perforation.
Resurfacing of the nasal lining with a free flap was planned. Total removal of
the nasal mucosa and remaining septum was conducted to make the nasal cavity into
one common cavity. Nasal passages were resurfaced with a radial forearm free
flap. Following surgery, the patient experienced no further significant
epistaxis. Fasciocutaneous free-flap resurfacing might represent a curative
solution for cases of HHT intractable to conservative treatment and
septodermoplasty, especially for patients with large septal perforation.
PMID- 27616748
TI - Siah-1 is associated with expression of hypoxia-inducible factor-1alpha in oral
squamous cell carcinoma.
AB - OBJECTIVE: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric basic helix-loop
helix transcription factor composed of the HIF-1alpha and HIF-1beta subunits. HIF
1 is a central regulator of responses to hypoxia; it enhances metastasis-related
factors such as matrix metalloproteinases and vascular endothelial growth factor
(VEGF). We have reported critical roles for HIF-1alpha in tumor
microenvironments, and oncogenic properties of HIF-1alpha have been suggested in
malignancies. Seven in absentia homologue (Siah) appeared to upregulate HIF-1
production, which prompted us to investigate the Siah association with HIF-1alpha
expression in oral squamous cell carcinoma (OSCC). METHODS: Samples from fifty
five patients with OSCC were evaluated by immunohistochemistry for the protein
expressions of Siah-1 and -2, HIF-1alpha, and VEGF. The expression levels of each
protein and clinicopathological data were statistically analyzed. RESULTS: Siah-1
and, Siah-2, HIF-1alpha, and VEGF were immunolocalized on the cell membranes and
cytoplasm of the tumor cells. The expression of Siah-1 showed a linear dependence
on the expression of HIF-1alpha (r=0.627, p<0.001). In 17 cases of the large
tumor size category (T3 and 4), the mean Siah-1 expression score was
significantly higher than in 41 cases of the small tumor size category (T1 and 2;
p=0.001). In addition, in 16 cases of the lymph node metastasis-positive category
(N1-3), the mean Siah-1 expression score was significantly higher than that in 42
cases of the lymph node metastasis-negative category (N0, p=0.001). CONCLUSION:
These results suggested that the expressions of Siah-1 and HIF-1alpha were
clearly correlated in OSCC. Moreover, Siah-1 appears to be correlated with
clinicopathological data, particularly tumor size.
PMID- 27616749
TI - Clinical and Diagnostic Imaging Features of Brain Herniation in Dogs and Cats.
AB - BACKGROUND: Quantification of brain herniation on MRI and its immediate clinical
implications are poorly described. OBJECTIVES: Define the normal position of
caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry,
compare this to dogs and cats with caudal transtentorial herniation (CTH),
foramen magnum herniation (FMH) or both identified on MRI, and investigate
associations between herniation severity, clinical signs, and 24-hour outcome.
ANIMALS: Ninety-two controls (66 dogs, 26 cats), 119 cases with herniation (88
dogs, 31 cats). METHODS: Retrospective case series. The MRI database was searched
for controls with normal brain anatomy and cases with brain herniation.
Morphometry in controls established TTX (transtentorial to rostroventral
cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum)
to quantify FMH. Measurements were compared between cases and controls.
Correlations with specific clinical variables and outcome were investigated.
RESULTS: Measurements in medium/large control dogs versus small dog and cat
controls were significantly different (P < .001, TTX: -0.46, -0.305, -0.3, FMX:
0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain
imaging had brain herniation. TTX and FMX were significantly different between
controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with
supratentorial lesions had no signs directly attributable to herniation. 71/119
(60%) had a normal anesthetic recovery. TTX was significantly associated with 24
hour survival (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Brain herniation
can be quantified on MRI. Clinical signs directly attributable to brain
herniation commonly are absent, and more severe CTH based on TTX is associated
with a worse short-term outcome.
PMID- 27616750
TI - Impaired activation of ALS monocytes by exosomes.
AB - Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative
disease affecting predominantly motor neurons in the spinal cord and motor
cortex. Neurodegeneration in ALS is accompanied by a well-characterized
neuroinflammatory reaction within the central nervous system and, as described
more recently, cells of the peripheral immune system. Particularly monocytes have
been implicated in ALS pathogenesis. Exosomes are membrane-enclosed vesicles
secreted by various cell types with a diameter of 50-150 nm. Circulating blood
exosomes have been shown to be important mediators and regulators of immunity.
Therefore, we hypothesize that circulating blood exosomes are putative mediators
of monocytic deregulation in ALS. Here we characterize exosomal uptake and the
respective immunological reaction of peripheral monocytes from ALS patients and
healthy donors using both serum-derived exosomes and TDP-43-loaded exosomes
produced in cell culture. We found the pro-inflammatory cytokine secretion by ALS
monocytes upon exosomal stimulation to be impaired compared with control
monocytes. Moreover, we demonstrate that exosomal TDP-43 induces increased
monocytic activation compared with non-aggregation-prone cargo. Therefore, this
study underlines the functional deregulation of ALS monocytes and the impact of
circulating blood exosomes on monocyte activation.
PMID- 27616751
TI - Anti-CD45RB and donor-specific spleen cells transfusion inhibition allograft skin
rejection mediated by memory T cells.
AB - Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known
as a barrier to the survival of transplanted organs. Selective interference with
the anti-CD45RB monoclonal antibody (alpha-CD45RB) reliably induces donor
specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with
the skin of female BLAB/c mice generated a large number of Tm cells and resulted
in rapid rejection of the secondly transplanted allografts. alpha-CD45RB did
induce the tolerance to skin allograft primarily transplanted but failed to
induce tolerance in the pre-sensitized mice. Donor-specific spleen cell
transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized
recipients. Interestingly, combination of alpha-CD45RB with DST inhibited the
rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell
depletion in alpha-CD45RB combined with DST therapy recipients could prevent skin
allograft tolerance from establishing. In addition, adoptive transfer of donor
primed memory T cells into the tolerant recipients markedly broke the established
tolerance. Our findings indicate that alpha-CD45RB and DST can synergistically
inhibit the accelerated rejection mediated by memory T cells and induce long-term
skin allograft acceptance in mice.
PMID- 27616752
TI - Quantitative high-throughput population dynamics in continuous-culture by
automated microscopy.
AB - We present a high-throughput method to measure abundance dynamics in microbial
communities sustained in continuous-culture. Our method uses custom epi
fluorescence microscopes to automatically image single cells drawn from a
continuously-cultured population while precisely controlling culture conditions.
For clonal populations of Escherichia coli our instrument reveals history
dependent resilience and growth rate dependent aggregation.
PMID- 27616753
TI - Reply to: Uniparental disomy of chromosome 1 unmasks recessive mutations of PPT1
in a boy with neuronal ceroid lipofuscinosis type 1.
PMID- 27616754
TI - Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis.
AB - Chronic kidney disease (CKD) is an increasingly recognized disease with high
global incidence and mortality. Yet, the existing diagnostic tools are not
sufficient enough to predict prognosis of CKD and CKD comorbidities. Indoxyl
sulfate, a typical uremic toxin, is of great importance in the development of CKD
with its nephrotoxicity, cardiovascular toxicity, and bone toxicity. Some reports
suggest that indoxyl sulfate directly associate with renal function loss and
mortality in CKD patients. This review discusses the diagnostic value of indoxyl
sulfate from its biological characteristics, pathophysiological effects, related
therapies, and its diagnostic value in clinical studies.
PMID- 27616756
TI - Vitamin D levels, vitamin D supplementation, and prognosis in patients with
chronic kidney disease?.
AB - BACKGROUND: Vitamin D (Vit D) deficiency plays a central role in the pathogenesis
of chronic kidney disease (CKD) complications, both skeletal and nonskeletal. The
purpose of this study was to examine whether 25(OH)D levels and supplementation
with oral cholecalciferol (Vitamin D3 (Vit D3)) are associated with morbidity and
mortality among patients with significant CKD. METHODS: CKD patients attending
the nephrology clinic at Shaare Zedek Medical Center between July 1, 2008 and
January 31, 2012, tested at least twice for 25(OH)D levels, were enrolled.
Primary endpoints included death, end-stage renal disease (ESRD) requiring start
of dialysis, a rise of at least 50% in serum creatinine, or composite endpoints
of the above. RESULTS: A total of 516 patients were studied, of whom 178, 257,
and 81 patients had baseline vitamin D levels < 5 ng/mL, 15 - 30 ng/mL, and > 30
ng/mL, respectively. We found an association between baseline 25(OH)D level below
15 ng/mL and renal outcomes (start of dialysis or a rise of at least 50% in serum
creatinine) in both crude and multivariate analyses (hazard ratio (HR) 3.17, 95%
CI 1.12 - 8.94). Vit D3 supplementation demonstrated beneficial effects on
combined renal outcomes and death in univariate analyses (p = 0.02). Moreover, an
increment of 10 ng/mL in 25(OH)D levels was associated with a 25% reduction in
mortality (HR 0.755 (95% CI 0.54 - 1.00), in crude but not adjusted analyses.
CONCLUSIONS: Significant Vit D deficiency in CKD can serve as a biological marker
indicating patients in whom adverse renal outcomes can be anticipated. Moreover,
Vit D3 supplementation and rise of serum 25(OH)D levels may have beneficial
influence on hard renal outcomes.?.
PMID- 27616755
TI - N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory
responses in vitro.
AB - Myocardial infarction (MI) leads to loss and degradation of contractile cardiac
tissue followed by sterile inflammation of the myocardium through activation and
recruitment of innate and adaptive cells of the immune system. Recently, it was
shown that cardiac myosin binding protein-C (cMyBP-C), a protein of the cardiac
sarcomere, is degraded following MI, releasing a predominant N-terminal 40-kDa
fragment (C0C1f) into myocardial tissue and the systemic circulation. We
hypothesized that early release of C0C1f contributes to the initiation of
inflammation and plays a key role in recruitment and activation of immune cells.
Therefore, we investigated the role of C0C1f on macrophage/monocyte activation
using both mouse bone marrow-derived macrophages and human monocytes. Here we
demonstrate that C0C1f leads to macrophage/monocyte activation in vitro.
Furthermore, C0C1f induces strong upregulation of pro-inflammatory cytokines
(interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin
1beta (IL-1beta)) in cultured murine macrophages and human monocytes, resulting
in a pro-inflammatory phenotype. We identified the toll-like receptor 4 (TLR4),
toll-like receptor 2 (TLR2), and Advanced Glycosylation End Product-Specific
Receptor (RAGE) as potential receptors for C0C1f whose activation leads to
mobilization of the NFkappaB signaling pathway, a central mediator of the pro
inflammatory signaling cascade. Thus, C0C1f appears to be a key player in the
initiation of inflammatory processes and might also play an important role upon
MI.
PMID- 27616757
TI - KDPI score is a strong predictor of future graft function: Moderate KDPI (35 -
85) and high KDPI (> 85) grafts yield similar graft function and survival?.
AB - BACKGROUND: Efforts have been made to maximize the utility of each organ
transplanted. Policy changes to capture unrealized graft years have been
implemented utilizing the kidney donor profile index (KDPI). Understanding the
impact of KDPI on long-term graft function is critical to an informed organ
acceptance decision. METHODS: We reviewed the records of 309 consecutive deceased
adult donor kidney recipients who underwent kidney transplantation at our center.
We obtained KDPI of the allografts directly from United Network for Organ Sharing
(UNOS) and patients were divided into four categories: KDPI <= 20, KDPI 21 - 35,
KDPI 36 - 85, and KDPI > 85. RESULTS: Of the 309 recipients, 48 (15.5%) received
kidneys from donors with KDPI <= 20, 57 (18.4%) from donors with KDPI 21 - 35,
161 (52.1%) from donors with KDPI 36 - 85, and 43 (13.9%) from donors with KDPI >
85. Older recipients were more likely to receive high KDPI kidneys (p = 0.025).
Kaplan-Meier analysis demonstrated the KDPI > 35 group had worse survival than
the KDPI <= 20 group, but KDPI 36 - 85 was not different from KDPI > 85. The rate
of poor graft function differed at 1 year: 14.6% of KDPI <= 20 recipients, 14.3%
of KDPI 21 - 35 recipients, 30.6% of KDPI 35 - 85 recipients, and 40.5% of KDPI >
85 recipients had serum creatinine greater than 2.0 mg/dL at 1 year. KDPI > 35
had statistically significantly greater incidence of poor graft function than
KDPI <= 35 (p < 0.05). CONCLUSIONS: Our study demonstrates that high KDPI grafts
behave more like moderate KDPI grafts (KDPI 35 - 85). Creatinine (Cr) greater
than 2.0 mg/dL portends poorer long-term graft survival, and this outcome is
similar amongst all recipients of KDPI > 35 allografts.?.
PMID- 27616758
TI - The effect of gender on aminoglycoside-associated nephrotoxicity?.
AB - AIMS: The kidney disease improving global outcomes (KDIGO) clinical practice
guidelines for acute kidney injury (AKI) has endorsed the widely held belief that
female gender is a risk factor for aminoglycoside-associated nephrotoxicity
(AAN). In contrast, female gender is protective in animal models. In light of
this dichotomy, we sought to explore this relationship in greater detail.
METHODS: We performed a meta-analysis of studies published between 1978 and 2015
which examined aminoglycoside nephrotoxicity and provided gender-specific data.
RESULTS: 24 studies were identified that provided univariate gender-specific
data. The incidence of AAN did not differ between the sexes (odds ratio (OR) for
females vs. males 1.00 (0.81, 1.22), p = 0.97, n = 5,980). Twelve studies
utilized logistic regression analysis with gender as a covariate. Meta-analysis
of the 5 studies that utilized multivariate analysis and reported gender-specific
OR found no effect of gender on the risk of AAN (OR 0.99 (0.58, 1.69), p = 0.96,
n = 2,994). Similarly, gender was not an independent risk factor for AAN in the
remaining 7 studies that utilized multivariate analysis with gender as a
covariate but failed to report gender-specific OR (n = 1,636). DISCUSSION: Our
meta-analysis contradicts the generally held consensus that female gender is an
independent risk factor for the development of AAN. Our findings may have much
wider implications insofar as AAN cannot be used as an example to support the
conclusion of the KDIGO Clinical Practice Guidelines that female gender is an
independent risk factor for AKI.?.
PMID- 27616759
TI - IL-1beta promotes tubulointerstitial injury in ?MPO-ANCA-associated
glomerulonephritis?.
AB - BACKGROUND: It is widely accepted that tubulointerstitial injury (TII) is caused
by glomerular injury (GI) in glomerular diseases. Glomerular endocapillary
inflammation may result in crescent formation and exuded protein leakage, which
may induce TII in antineutrophil cytoplasmic antibody-associated
glomerulonephritis (ANCAGN). However, some reports have indicated a
glomerulonephritis-independent mechanism of TII in ANCAGN. The aim of this study
was to determine the principle cytokines correlated with TII severity and to
elucidate a characteristic mechanism for TII in ANCAGN. METHODS: 28
myeloperoxidase-ANCA-positive ANCAGN patients were enrolled, and their kidney
biopsy specimens were histologically evaluated with regard to GI and TII. The
mRNA expression of various cytokines was examined in 28 specimens. RESULTS:
Interleukin (IL)-1beta was significantly correlated with the severity of TII. The
mRNA expression of Toll-like receptor 4 (TLR4) and Nod-like receptor family pyrin
domain-containing-3 (NLRP3) also correlated with TII severity.
Immunohistochemical analysis demonstrated that TLR4 protein was positively
stained in the tubulointerstitial infiltrating cells. NRLP3 protein was detected
in macrophages in the severe infiltrating area but was absent or only very
faintly expressed in the glomeruli. These results indicated that NLRP3
inflammasome-dependent processing in macrophages releases the mature active form
of IL-1beta, which may lead to the development and deterioration of TII.
CONCLUSIONS: Sterile inflammation leads to the formation of ANCA-mediated
neutrophil extracellular traps (NETs), which may stimulate macrophages and
dendritic cells via TLR4 and induce NF-kappaB-dependent mRNA expression and
translation of pro-IL-1beta. Simultaneously, damage-associated molecular pattern
signals resulting from NETs promote NLRP3 inflammasome-dependent processing and
release mature active IL-1beta. Sterile inflammation utilizing the NLRP3
inflammasome might be a characteristic reaction limited to the
tubulointerstitium. Thus, neutralizing IL-1beta may be a promising strategy to
suspend the progress of TII and improve the prognosis of chronic kidney disease
resulting from ANCAGN.?.
PMID- 27616760
TI - Prevention of recurrence of atypical hemolytic uremic syndrome post renal
transplant with the use of higher-dose eculizumab?.
AB - Eculizumab, a terminal complement inhibitor, has recently been used successfully
to both prevent and treat the recurrence of atypical hemolytic uremic syndrome
(aHUS) post renal transplantation. We describe a case that highlights the need to
monitor the effects of eculizumab on the complement system and in this case alter
the dosage. Despite taking the standard recommended dose of eculizumab for an
adult, this aHUS patient developed a low-grade thrombotic microangiopathy on
biopsy within months of renal transplantation. Complement assays (trough CH50)
showed small amounts of residual terminal pathway activity suggesting inadequate
complement blockade on 1,200 mg eculizumab every 2 weeks. Following an increase
in the dose of eculizumab to 1,500 mg every 2 weeks, lactate dehydrogenase (LDH),
proteinuria, and creatinine decreased, and CH50 assay showed 0%. This case
emphasizes the need to monitor clinical parameters and complement activity to
ensure that adequate therapeutic blockade is achieved.?.
PMID- 27616761
TI - A systematic literature search and review of sodium concentrations of body
fluids?.
AB - BACKGROUND: Wide ranges of sodium concentrations for different body fluid losses
have been noted with minimal substantiating data and variability among sources,
leading to use of "cumulative fluid balance" regardless of composition in
hospitalized patients. AIMS: To define the sodium concentrations of fluid losses
from the body. METHOD: We performed a systematic search and literature review in
adult humans using PubMed database. RESULTS: Inclusion criteria were met for 107
full-text articles. Mean sodium concentrations were significantly lower for
acidic (mean +/- SD: 44 +/- 12 mEq/L) than for alkaline (55 +/- 13 mEq/L) gastric
fluid, higher for bile (185 +/- 24 mEq/L) or pancreatic fluid (156 +/- 3 mEq/L)
than for all other body fluids, and similar for intact small bowel (119 +/- 14
mEq/L) and ileostomy outputs (116 +/- 25 mEq/L). Sodium concentrations were
significantly greater for cholera-induced diarrhea (128 +/- 18 mEq/L) and lower
for osmotic-induced diarrhea (28 +/- 16 mEq/L) than all other causes of diarrhea.
For osmotic diarrheas, sorbitol-induced diarrhea sodium concentration was higher
(63 +/- 17 mEq/L) than for carbohydrate malabsorption (43 +/- 20 mEq/L),
lactulose (26 +/- 19 mEq/L), Idolax (16 +/- 13 mEq/L), or polyethylene glycol (13
+/- 7 mEq/L). For secretory diarrheas, sodium concentration for idiopathic causes
(53 +/- 22 mEq/L) was lower than for neuroendocrine and villous tumors (75 +/- 13
mEq/L) or nonosmotic laxatives (88 +/- 33 mEq/L). For pleural, peritoneal, and
edema fluid, sodium concentrations (137 +/- 13 mEq/L) were similar to plasma. No
data were found for wound fluid. Sodium concentration for sweat was 44 +/- 17
mEq/L. CONCLUSIONS: This is the first in-depth review of verifiable sodium
concentrations of body fluids most commonly lost in hospitalized patients. Sodium
concentrations are fluid-specific and consistent. Sodium concentrations for
diarrhea are associated with specific mechanisms/causes. These data should be
useful to more accurately replace sodium and water content for specific body
fluid losses.?.
PMID- 27616762
TI - Icodextrin-induced acute pancreatitis in a peritoneal dialysis patient: a case
report and literature review?.
AB - The 7.5% icodextrin solution is widely used for long-dwell in peritoneal dialysis
(PD) regimens as an alternative osmotic agent to glucose. It has been defined as
a biocompatible agent because of its iso-osmolarity and is generally safe and
well tolerated. Icodextrin and its hydrolyzed metabolites are found in systemic
circulation. In serum, icodextrin interferes with amylase determination causing a
significantly decreased plasma amylase level making it unreliable for the
diagnosis of acute pancreatitis. Lipase measurement provides an alternative and
accurate method for diagnosing acute pancreatitis (AP) in patients using
icodextrin. Icodextrin-induced acute pancreatitis is not well described. The
literature appears limited to two case reports. We describe a case of a man with
end-stage renal disease (ESRD) on PD who developed acute pancreatitis following
icodextrin use. We also provide a novel possible mechanism for understanding how
icodextrin causes AP.?.
PMID- 27616763
TI - Bacterial and Yeast AAA+ Disaggregases ClpB and Hsp104 Operate through Conserved
Mechanism Involving Cooperation with Hsp70.
AB - Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are members of the
Hsp100 family of ring-forming hexameric AAA+ chaperones that promote the
solubilization of aggregated proteins and the propagation of prions. ClpB and
Hsp104 cooperate with cognate Hsp70 chaperones for substrate targeting and
activation of ATPase and substrate threading, achieved by transient Hsp70 binding
to the repressing ClpB/Hsp104 M-domain. Fundamental differences in ATPase
regulation and disaggregation mechanisms have been reported; however, these
differences are raising doubts regarding the working principle of this AAA+
chaperone. In particular, unique functional plasticity was suggested to
specifically enable Hsp104 to circumvent Hsp70 requirement for derepression in
protein disaggregation and prion propagation. We show here that both ClpB and
Hsp104 cooperation with Hsp70 is crucial for efficient protein disaggregation
and, in contrast to earlier claims, cannot be circumvented by activating M-domain
mutations. Activation of ClpB and Hsp104 requires two signals, relief of M-domain
repression and substrate binding, leading to increased ATPase subunit coupling.
These data demonstrate that ClpB and Hsp104 operate by the same basic mechanism,
underscore a dominant function of Hsp70 in regulating ClpB/Hsp104 activity, and
explain a plethora of in vivo studies showing a crucial function of Hsp70 in
proteostasis and prion propagation.
PMID- 27616764
TI - Damage Patterns, Monitoring, and Management of Procontarinia mangiferae (Diptera:
Cecidomyiidae) in Pakistan.
AB - Since 2005, mango has been damaged by a group of new pests, the gall midges, in
all mango-growing areas of Pakistan. Little is known about these pests in
Pakistan. In this report, we present information on the occurrence, damage
patterns, methods for monitoring, and management of Procontarinia mangiferae
(Felt), a mango gall midge found in the country. At the study site (Rahim Yar
Khan, a district of the province Punjab, Pakistan), the pest was active from
January/February to April as eggs, larvae, and adults on mango inflorescence
buds, branches (axillaries), and immature fruits. Females of P. mangiferae
oviposited in inflorescence tissues, and larvae, after feeding on plant tissues,
dropped to the soil under the mango trees for pupation from February to April.
Mango trees in commercial orchards were more heavily damaged by P. mangiferae
than were isolated trees in farmer fields (66.7%). The adults of P. mangiferae
were captured on sticky traps of all tested colors, and were in flight from
January to May. Captures per trap were highest on yellow traps, followed by
green, blue, and clear traps. Control of mango gall midge was effectively
provided by the synthetic insecticide bifenthrin (Talstar 10 EC) and also by
application of neem seed kernel extract on the tree canopy if integrated with
raking the soil under the mango tree canopy.
PMID- 27616766
TI - Innate and Learned Responses of the Tephritid Parasitoid Psyttalia concolor
(Hymenoptera: Braconidae) to Olive Volatiles Induced by Bactrocera oleae
(Diptera: Tephritidae) Infestation.
AB - Parasitic wasps can learn cues that alter their behavioral responses and increase
their fitness, such as those that improve host location efficiency. Psyttalia
concolor (Szepligeti) (Hymenoptera: Braconidae) is a koinobiont endoparasitoid of
14 economically important tephritid species, including the olive fruit fly,
Bactrocera oleae (Rossi) (Diptera: Tephritidae). In this research, we
investigated the nature of olfactory cues mediating this tritrophic interaction.
First, we identified the chemical stimuli emanating from uninfested and B. oleae
infested olive fruits via solid phase microextraction and gas chromatography-mass
spectrometry analyses and identified >70 volatile organic compounds (VOCs). Two
of these were increased by B. oleae infestation, (E)-beta-ocimene and 2-methyl-6
methylene-1,7-octadien-3-one, and four were decreased, alpha-pinene, beta-pine
ne, limonene, and beta-elemene. Innate positive chemotaxis of mated P. concolor
females toward these VOCs was then tested in olfactometer assays. Females were
attracted only by (E)-beta-ocimene, at both tested dosages, indicating an
intrinsic response to this compound as a short-range attractant. Next, we tested
whether mated P. concolor females could learn to respond to innately unattractive
VOCs if they were first presented with a food reward. Two nonassociative controls
were conducted, i.e., "odor only" and "reward only." Following training, females
showed positive chemotaxis toward these VOCs in all tested combinations, with the
exception of limonene, a VOC commonly produced by flowers. Control females showed
no significant preferences, indicating that positive associative learning had
occurred. These results clarify how learned cues can fine-tune innate responses
to B. oleae-induced VOCs in this generalist parasitoid of tephritid flies.
PMID- 27616767
TI - Partner relationship, social support and perinatal distress among pregnant
Icelandic women.
AB - BACKGROUND: It is inferred that perinatal distress has adverse effects on the
prospective mother and the health of the foetus/infant. More knowledge is needed
to identify which symptoms of perinatal distress should be assessed during
pregnancy and to shed light on the impact of women's satisfaction with their
partner relationship on perinatal distress. AIM: The current study aimed to
generate knowledge about the association of the partner relationship and social
support when women are dealing with perinatal distress expressed by symptoms of
depression, anxiety and stress. METHODS: A structured interview was conducted
with 562 Icelandic women who were screened three times during pregnancy with the
Edinburgh Depression Scale and the Depression, Anxiety, Stress Scale. Of these,
360 had symptoms of distress and 202 belonged to a non-distress group. The women
answered the Multidimensional Scale of Perceived Social Support and the Dyadic
Adjustment Scale. The study had a multicentre prospective design allowing for
exploration of association with perinatal distress. FINDINGS: Women who were
dissatisfied in their partner relationship were four times more likely to
experience perinatal distress. Women with perinatal distress scored highest on
the DASS Stress Subscale and the second highest scores were found on the Anxiety
Subscale. CONCLUSION: Satisfaction in partner relationship is related to
perinatal distress and needs to be assessed when health care professionals take
care of distressed pregnant women, her partner and her family. Assessment of
stress and anxiety should be included in the evaluation of perinatal distress,
along with symptoms of depression.
PMID- 27616768
TI - Ultrahigh Purcell factor in low-threshold nanolaser based on asymmetric hybrid
plasmonic cavity.
AB - A low-threshold nanolaser with all three dimensions at the subwavelength scale is
proposed and investigated. The nanolaser is constructed based on an asymmetric
hybrid plasmonic F-P cavity with Ag-coated end facets. Lasing characteristics are
calculated using finite element method at the wavelength of 1550 nm. The results
show that owing to the low modal loss, large modal confinement factor of the
asymmetric plasmonic cavity structure, in conjunction with the high reflectivity
of the Ag reflectors, a minimum threshold gain of 240 cm(-1) is predicted.
Furthermore, the Purcell factor as large as 2518 is obtained with optimized
structure parameters to enhance rates of spontaneous and stimulated emission.
PMID- 27616769
TI - Antibiotic resistance.
AB - Antimicrobial resistance in bacterial pathogens is a challenge that is associated
with high morbidity and mortality. Multidrug resistance patterns in Gram-positive
and -negative bacteria are difficult to treat and may even be untreatable with
conventional antibiotics. There is currently a shortage of effective therapies,
lack of successful prevention measures, and only a few new antibiotics, which
require development of novel treatment options and alternative antimicrobial
therapies. Biofilms are involved in multidrug resistance and can present
challenges for infection control. Virulence, Staphylococcus aureus, Clostridium
difficile infection, vancomycin-resistant enterococci, and control in the
Emergency Department are also discussed.
PMID- 27616770
TI - Discrepancies with the bibliometric assessment of Mayaro-related publications.
PMID- 27616771
TI - Impact of type 2 diabetes mellitus on the incidence of malaria.
PMID- 27616772
TI - Acute illness with neurological findings caused by coinfection of dengue and
chikungunya viruses in a Brazilian patient.
PMID- 27616773
TI - Addressing Inconsistencies in the Social Norms Drinking Literature: Development
of the Injunctive Norms Drinking and Abstaining Behaviors Questionnaire.
AB - BACKGROUND: Informed by inconsistent findings regarding the association between
injunctive norms (IN) and drinking behaviors, the current study developed a new
measure of IN, the Injunctive Norms Drinking and Abstaining Behaviors
Questionnaire (IN-DABQ). This measure addressed several psychometric weaknesses
of prior assessment of this construct, specifically, reliance on single-item
measures, and assessment of a limited range of drinking behaviors. The new
measure also assessed norms for reasons for abstaining from drinking as college
students often have simultaneous motives to use and inhibit their drug use. A
parallel measure of descriptive norms (DN), the Descriptive Norms Drinking and
Abstaining Behaviors Questionnaire (DN-DABQ), was created to allow for a
comparison of the relative predictive effects of descriptive and IN in relation
to different drinking outcomes. METHODS: A college sample (N = 254, female =
50.42%) was recruited using Amazon's Mechanical Turk. Participants completed an
online survey assessing demographic characteristics, social norms for 3
referents, weekly alcohol use, and alcohol-related consequences. RESULTS:
Exploratory factor analyses indicated 2 factors for the DN-DABQ and 3 factors for
the IN-DABQ. The IN Drinking Behaviors factor consistently predicted weekly
consumption and alcohol-related consequences across 3 reference groups (typical
college student at your school, friends, and closest friends). CONCLUSIONS: These
findings suggest that prior inconsistencies in the relationship between IN and
drinking behaviors are likely a function of poor measurement of this construct.
Implications for normative feedback interventions are discussed.
PMID- 27616774
TI - First report of "Candidatus Rickettsia amblyommii" in west coast of Mexico.
AB - We report the first case of "Candidatus Rickettsia amblyommii" detected in
Amblyomma mixtum ticks on humans on the west coast of Mexico. This is the most
western record of "Ca. R. amblyommii" in the Western Hemisphere, representing the
first record for the western coast of the Americas. Even if the record is far
from the previously known locations for the species it does not represent a new
record regarding temperature, precipitation and topographic parameters. Since
"Ca. R. amblyommii" antibodies have been detected in patients suspected of Rocky
Mountain spotted fever, and the tick A. mixtum has been associated with humans,
it is important to consider "Ca. R. amblyommii" as a potential risk for the human
population that has not been considered at risk before.
PMID- 27616777
TI - A supernumerary ventricular cavity.
PMID- 27616778
TI - Extensive cardiac infiltration in acute T-cell lymphoblastic leukemia: occult
extra-medullary relapse and remission after salvage chemotherapy.
PMID- 27616775
TI - PGD: a pangolin genome hub for the research community.
AB - Pangolins (order Pholidota) are the only mammals covered by scales. We have
recently sequenced and analyzed the genomes of two critically endangered Asian
pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese
pangolin (Manis pentadactyla). These complete genome sequences will serve as
reference sequences for future research to address issues of species conservation
and to advance knowledge in mammalian biology and evolution. To further
facilitate the global research effort in pangolin biology, we developed the
Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and
transcriptomic data and annotations, and with useful analysis tools for the
research community. Currently, the PGD provides the reference pangolin genome and
transcriptome data, gene sequences and functional information, expressed
transcripts, pseudogenes, genomic variations, organ-specific expression data and
other useful annotations. We anticipate that the PGD will be an invaluable
platform for researchers who are interested in pangolin and mammalian research.
We will continue updating this hub by including more data, annotation and
analysis tools particularly from our research consortium.Database URL:
http://pangolin-genome.um.edu.my.
PMID- 27616779
TI - Incomplete Shone's complex in the sixth decade of life: echo and cardiac magnetic
resonance imaging assessment.
PMID- 27616780
TI - Anatomy and histochemistry of spread-wing posture inbirds. 4. Eagles soar with
fast, not slow muscle fibres.
AB - Slow fibers are typically characterized as functioning in avian postural
behaviors such as soaring flight, and are described for a number of elite soarers
such as vultures, pelicans and albatrosses. Golden Eagles and Bald Eagles also
display soaring behavior and we examined their flight muscles for the presence of
slow fibers. Surprisingly, eagles lack a deep layer to the pectoralis found in
other soaring species. Additionally, the pectoralis as well as other shoulder
muscles had few to no slow muscle fibers. The lack of functionally meaningful
numbers of slow muscle fibers in eagle flight muscles indicates that they must
rely on fast fibers for posture; these can function in that role due to their
high aerobic capacity and also perhaps a "tuning" of muscle contraction frequency
to function more efficiently at isometric contractions.
PMID- 27616781
TI - Automated Mini-Column Solid-Phase Extraction Cleanup for High-Throughput Analysis
of Chemical Contaminants in Foods by Low-Pressure Gas Chromatography-Tandem Mass
Spectrometry.
AB - This study demonstrated the application of an automated high-throughput mini
cartridge solid-phase extraction (mini-SPE) cleanup for the rapid low-pressure
gas chromatography-tandem mass spectrometry (LPGC-MS/MS) analysis of pesticides
and environmental contaminants in QuEChERS extracts of foods. Cleanup
efficiencies and breakthrough volumes using different mini-SPE sorbents were
compared using avocado, salmon, pork loin, and kale as representative matrices.
Optimum extract load volume was 300 uL for the 45 mg mini-cartridges containing
20/12/12/1 (w/w/w/w) anh. MgSO4/PSA (primary secondary amine)/C18/CarbonX
sorbents used in the final method. In method validation to demonstrate high
throughput capabilities and performance results, 230 spiked extracts of 10
different foods (apple, kiwi, carrot, kale, orange, black olive, wheat grain,
dried basil, pork, and salmon) underwent automated mini-SPE cleanup and analysis
over the course of 5 days. In all, 325 analyses for 54 pesticides and 43
environmental contaminants (3 analyzed together) were conducted using the 10 min
LPGC-MS/MS method without changing the liner or retuning the instrument. Merely,
1 mg equivalent sample injected achieved <5 ng g-1 limits of quantification. With
the use of internal standards, method validation results showed that 91 of the 94
analytes including pairs achieved satisfactory results (70-120 % recovery and RSD
<= 25 %) in the 10 tested food matrices (n = 160). Matrix effects were typically
less than +/-20 %, mainly due to the use of analyte protectants, and minimal
human review of software data processing was needed due to summation function
integration of analyte peaks. This study demonstrated that the automated mini-SPE
+ LPGC-MS/MS method yielded accurate results in rugged, high-throughput
operations with minimal labor and data review.
PMID- 27616782
TI - Development and Validation of a UHPLC UV Method for the In-Process Control of
Bosentan Monohydrate Synthesis.
AB - Bosentan monohydrate (4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2
(pyrimidin-2-yl) pyrimidin-4-yl]benzene-1-sulfonamide monohydrate) is a dual
endothelin receptor antagonist (ERA) applied in the treatment of pulmonary
arterial hypertension. To achieve effective process control of the bosentan
monohydrate synthesis, it was necessary to develop a selective and not highly
time-consuming method for ultra-high performance liquid chromatography (UHPLC).
The method is characterized by adequate sensitivity, reproducibility and
selectivity for the determination of bosentan monohydrate and related compounds
from all synthetic stages. The UHPLC separation was carried out by reversed phase
chromatography on the Acquity BEH C18 column (100 mm * 2.1 mm, 1.7 um) with a
mobile phase composed of solvent A (0.1 %, v/v, acetic acid in water) and solvent
B (methanol), in the gradient mode at the flow rate of 0.4 mL min-1. Limits of
detection and quantification for the compounds were <=0.1 ug mL-1 and 0.3 ug mL
1, respectively. The linearity for all related compounds was investigated as in
the range for the active pharmaceutical ingredient (API) and as in the range for
the in-process control. The developed method was validated according to the
current guidelines, proving the suitability of the method for its intended
purpose.
PMID- 27616783
TI - Is it all worth it? The experiences of new PhDs on the job market, 2007-10.
AB - This paper describes the job market experiences of new PhD economists, 2007-10.
Using information from PhD programs' job candidate websites and original surveys,
the authors present information about job candidates' characteristics,
preferences and expectations; how job candidates fared at each stage of the
market; and predictors of outcomes at each stage. Some information presented in
this paper updates findings of prior studies. However, design features of the
data used in this paper may result in more generalizable findings. This paper is
unique in comparing pre-market expectations and preferences with post-market
outcomes on the new PhD job market. It shows that outcomes tend to align with pre
market preferences, and candidates' expectations are somewhat predictive of their
outcomes. Several analyses also shed light on sub-group differences.
PMID- 27616784
TI - Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment
Response?
AB - OBJECTIVE: No previous empirical study has investigated whether the LD
identification decisions of proposed methods to operationalize processing
strengths and weaknesses (PSW) approaches for LD identification are associated
with differential treatment response. We investigated whether the identification
decisions of the concordance/discordance model (C/DM; Hale & Fiorello, 2004) and
Cross Battery Assessment approach (XBA method; Flanagan, Ortiz, & Alfonso, 2007)
were consistent and whether they predicted intervention response beyond that
accounted for by pretest performance on measures of reading. METHOD:
Psychoeducational assessments were administered at pretest to 203 4th graders
with low reading comprehension and individual results were utilized to identify
students who met LD criteria according to the C/DM and XBA methods and students
who did not. Resulting group status permitted an investigation of agreement for
identification methods and whether group status at pretest (LD or not LD) was
associated with differential treatment response to an intensive reading
intervention. RESULTS: The LD identification decisions of the XBA and C/DM
demonstrated poor agreement with one another (kappa = -.10). Comparisons of
posttest performance for students who met LD criteria and those who did not meet
were largely null, with small effect sizes across all measures. CONCLUSIONS: LD
status, as identified through the C/DM and XBA approaches, was not associated
with differential treatment response and did not contribute educationally
meaningful information about how students would respond to intensive reading
intervention. These results do not support the value of cognitive assessment
utilized in this way as part of the LD identification process.
PMID- 27616785
TI - My Pride and Joy? Predicting Favoritism and Disfavoritism in Mother-Adult Child
Relations.
AB - In this article, we compare predictors of mothers' differentiation among their
adult children regarding emotional closeness, pride, conflict, and
disappointment. We distinguish between predictors of relational (closeness,
conflict) and evaluative (pride, disappointment) dimensions of favoritism and
disfavoritism. Multilevel modeling using data collected from 381 older mothers
regarding their relationships with 1,421 adult children indicated that adult
children's similarity of values played the most prominent role in predicting
mothers' favoritism and disfavoritism, followed by children's gender. Children's
deviant behaviors in adulthood predicted both pride and disappointment but
neither relational dimension. Contrary to expectations, the quantitative analysis
indicated that children's normative adult achievements were poor predictors of
both relational and evaluative dimensions of mothers' differentiation.
Qualitative data shed additional light on mothers' evaluations by revealing that
disappointment was shaped by children's achievements relative to their mothers'
values and expectations, rather than by the achievement of specific societal,
educational, career, and marital milestones.
PMID- 27616786
TI - Redefining Microascus, Scopulariopsis and allied genera.
AB - The genera Microascus and Scopulariopsis comprise species commonly isolated from
soil, decaying plant material and indoor environments. A few species are also
recognised as opportunistic pathogens of insects and animals, including humans.
In the past, the taxonomy of these fungi has been based on morphology only. With
the aim to clarify the taxonomy and phylogeny of these fungi, we studied a large
set of clinical and environmental isolates, including the available ex-type
strains of numerous species, by means of morphological, physiological and
molecular analyses. Species delineation was assessed under the Genealogical
Phylogenetic Species Recognition (GCPSR) criterion using DNA sequence data of
four loci (ITS region, and fragments of rDNA LSU, translation elongation factor 1
alpha and beta-tubulin). The genera Microascus and Scopulariopsis were found to
be separated in two distinct lineages. The genus Pithoascus is reinstated and the
new genus Pseudoscopulariopsis is erected, typified by P. schumacheri. Seven new
species of Microascus and one of Scopulariopsis are described, namely M.
alveolaris, M. brunneosporus, M. campaniformis, M. expansus, M. intricatus, M.
restrictus, M. verrucosus and Scopulariopsis cordiae. Microascus trigonosporus
var. macrosporus is accepted as a species distinct from M. trigonosporus. Nine
new combinations are introduced. Microascus cinereus, M. longirostris, P.
schumacheri and S. flava are neotypified. A table summarising the morphological
features of the species treated and identification keys for each genus are
provided.
PMID- 27616787
TI - Taxonomic re-evaluation of species in Talaromyces section Islandici, using a
polyphasic approach.
AB - The taxonomy of Talaromyces rugulosus, T. wortmannii and closely related species,
classified in Talaromyces sect. Islandici, is reviewed in this paper. The species
of Talaromyces sect. Islandici have restricted growth on MEA and CYA, generally
have yellow mycelia and produce rugulosin and/or skyrin. They are important in
biotechnology (e.g. T. rugulosus, T. wortmannii) and in medicine (e.g. T. piceus,
T. radicus). The taxonomy of sect. Islandici was resolved using a combination of
morphological, extrolite and phylogenetic data, using the Genealogical
Concordance Phylogenetic Species Recognition (GCPSR) concept, with special focus
on the T. rugulosus and T. wortmannii species complexes. In this paper, we
synonymise T. variabilis, Penicillium concavorugulosum and T. sublevisporus with
T. wortmannii, and introduce four new species as T. acaricola, T. crassus, T.
infraolivaceus and T. subaurantiacus. Finally, we provide a synoptic table for
the identification of the 19 species classified in the section.
PMID- 27616788
TI - Taxonomic and phylogenetic re-evaluation of Microdochium, Monographella and
Idriella.
AB - Based on morphology and DNA sequence data the taxonomic relationships of
Microdochium, Monographella and Idriella were reassessed. Microdochium is
morphologically and phylogenetically circumscribed, and the sexual genus
Monographella treated as synonym on the basis that Microdochium has more species,
is more commonly encountered, and more frequently used in literature. An epitype
is designated for Microdochium phragmites, and several well-known species are
redefined based on their morphology and DNA sequence data (LSU, ITS, BTUB and
RPB2). Furthermore, the revision of Microdochium led to six new combinations (M.
albescens, M. consociatum, M. fusariisporum, M. maydis, M. opuntiae and M.
stevensonii) and six new species (M. citrinidiscum, M. colombiense, M. fisheri,
M. neoqueenslandicum, M. seminicola and M. trichocladiopsis) being proposed.
Microdochium s.str. belongs to a monophyletic clade, together with Idriella
lunata and Selenodriella, representing a new family, Microdochiaceae, in
Xylariales. Other species previously accommodated in Microdochium belong to
different orders in the Ascomycota. Microdochium gracile belongs to
Sordariomycetes (incertae sedis) and Paramicrodochium is proposed to accommodate
this species. Microdochium tripsaci belongs to Ephelis in Clavicipitaceae, while
M. fusarioides belongs to a new genus, Microdochiella in Orbiliales. Idriella
s.str. is a monotypic genus phylogenetically closely related to Microdochium.
Idriella s.l. separates into different genera in Xylariales (incertae sedis)
including Castanediella, Selenodriella, Idriellopsis, Neoidriella and
Paraidriella, the last three proposed here as new genera.
PMID- 27616789
TI - Phylogenetic reassessment of the Chaetomium globosum species complex.
AB - Chaetomium globosum, the type species of the genus, is ubiquitous, occurring on a
wide variety of substrates, in air and in marine environments. This species is
recognised as a cellulolytic and/or endophytic fungus. It is also known as a
source of secondary metabolites with various biological activities, having great
potential in the agricultural, medicinal and industrial fields. On the negative
side, C. globosum has been reported as an air contaminant causing adverse health
effects and as causal agent of human fungal infections. However, the taxonomic
status of C. globosum is still poorly understood. The contemporary species
concept for this fungus includes a broadly defined morphological diversity as
well as a large number of synonymies with limited phylogenetic evidence. The aim
of this study is, therefore, to resolve the phylogenetic limits of C. globosum
s.str. and related species. Screening of isolates in the collections of the CBS
KNAW Fungal Biodiversity Centre (The Netherlands) and the China General
Microbiological Culture Collection Centre (China) resulted in recognising 80
representative isolates of the C. globosum species complex. Thirty-six species
are identified based on phylogenetic inference of six loci, supported by typical
morphological characters, mainly ascospore shape. Of these, 12 species are newly
described here. Additionally, C. cruentum, C. mollipilium, C. rectum, C.
subterraneum and two varieties of C. globosum are synonymised under C. globosum
s.str., and six species are resurrected, i.e. C. angustispirale, C. coarctatum,
C. cochliodes, C. olivaceum, C. spiculipilium and C. subglobosum. Chaetomium
ascotrichoides is segregated from C. madrasense and the genus name Chaetomidium
is rejected. Five species, including C. globosum s.str., are typified here to
stabilise their taxonomic status. A further evaluation of the six loci used in
this study as potential barcodes indicated that the 28S large subunit (LSU) nrDNA
and the internal transcribed spacer regions and intervening 5.8S nrRNA (ITS) gene
regions were unreliable to resolve species, whereas beta-tubulin (tub2) and RNA
polymerase II second largest subunit (rpb2) showed the greatest promise as DNA
barcodes for differentiating Chaetomium species. This study provides a starting
point to establish a more robust classification system for Chaetomium and for the
Chaetomiaceae.
PMID- 27616790
TI - A taxonomic review of Penicillium species producing conidiophores with solitary
phialides, classified in section Torulomyces.
AB - The genus Torulomyces was characterised by species that typically have
conidiophores consisting of solitary phialides that produce long chains of
conidia connected by disjunctors. Based on the phylogenetic position of P. lagena
(generic ex-neotype), the genus and its seven species were transferred to
Penicillium and classified in sect. Torulomyces along with P. cryptum and P.
lassenii. The aim of this study was to review the species currently classified in
sect. Torulomyces using morphology and phylogenies of the ITS, BenA, CaM and RPB2
regions. Based on our results, we accept 16 species in sect. Torulomyces,
including 12 new species described as P. aeris, P. austricola, P. cantabricum, P.
catalonicum, P. oregonense, P. marthae-christenseniae, P. riverlandense, P.
tubakianum, P. variratense, P. williamettense, P. wisconsinense and P.
wollemiicola. In addition, we reclassify P. laeve and P. ovatum in sect.
Exilicaulis and correct the typification of P. lagena. We provide descriptions
and notes on the identification of the species.
PMID- 27616792
TI - Fifteen new species of Penicillium.
AB - We introduce 15 new species of Penicillium isolated from a diverse range of
locations, including Canada, Costa Rica, Germany, Italy, New Zealand, Tanzania,
USA and the Dry Valleys of Antarctica, from a variety of habitats, including leaf
surfaces in tropical rain forests, soil eaten by chimpanzees, infrabuccal pockets
of carpenter ants, intestinal contents of caterpillars and soil. The new species
are classified in sections Aspergilloides (1), Canescentia (2), Charlesia (1),
Exilicaulis (3), Lanata-Divaricata (7) and Stolkia (1). Each is characterised and
described using classical morphology, LC-MS based extrolite analyses and
multigene phylogenies based on ITS, BenA and CaM. Significant extrolites detected
include andrastin, pulvilloric acid, penitrem A and citrinin amongst many others.
PMID- 27616791
TI - Generic hyper-diversity in Stachybotriaceae.
AB - The family Stachybotriaceae was recently introduced to include the genera
Myrothecium, Peethambara and Stachybotrys. Members of this family include
important plant and human pathogens, as well as several species used in
industrial and commercial applications as biodegraders and biocontrol agents.
However, the generic boundaries in Stachybotriaceae are still poorly defined, as
type material and sequence data are not readily available for taxonomic studies.
To address this issue, we performed multi-locus phylogenetic analyses using
partial gene sequences of the 28S large subunit (LSU), the internal transcribed
spacer regions and intervening 5.8S nrRNA (ITS), the RNA polymerase II second
largest subunit (rpb2), calmodulin (cmdA), translation elongation factor 1-alpha
(tef1) and beta-tubulin (tub2) for all available type and authentic strains.
Supported by morphological characters these data resolved 33 genera in the
Stachybotriaceae. These included the nine already established genera Albosynnema,
Alfaria, Didymostilbe, Myrothecium, Parasarcopodium, Peethambara,
Septomyrothecium, Stachybotrys and Xepicula. At the same time the generic names
Melanopsamma, Memnoniella and Virgatospora were resurrected. Phylogenetic
inference further showed that both the genera Myrothecium and Stachybotrys are
polyphyletic resulting in the introduction of 13 new genera with myrothecium-like
morphology and eight new genera with stachybotrys-like morphology.
PMID- 27616793
TI - New species of Cladosporium associated with human and animal infections.
AB - Cladosporium is mainly known as a ubiquitous environmental saprobic fungus or
plant endophyte, and to date, just a few species have been documented as
etiologic agents in vertebrate hosts, including humans. In the present study, 10
new species of the genus were isolated from human and animal clinical specimens
from the USA. They are proposed and characterized on the basis of their
morphology and a molecular phylogenetic analysis using DNA sequences from three
loci (the ITS region of the rDNA, and partial fragments of the translation
elongation factor 1-alpha and actin genes). Six of those species belong to the C.
cladosporioides species complex, i.e., C. alboflavescens, C. angulosum, C.
anthropophilum, C. crousii, C. flavovirens and C. xantochromaticum, three new
species belong to the C. herbarum species complex, i.e., C. floccosum, C.
subcinereum and C. tuberosum; and one to the C. sphaerospermum species complex,
namely, C. succulentum. Differential morphological features of the new taxa are
provided together with molecular barcodes to distinguish them from the currently
accepted species of the genus.
PMID- 27616794
TI - New sections in Penicillium containing novel species producing patulin,
pyripyropens or other bioactive compounds.
AB - Subgenera and sections have traditionally been used in Penicillium
classifications. In the past, this sectional classification was based on macro-
and microscopic characters, and occasionally supplemented with physiological
and/or extrolite data. Currently, 25 sections are accepted, largely based on
phylogenetic data. Certain sections of subgenus Penicillium were never studied in
detail using a multigene sequence approach combined with phenotypic, ecological
and extrolite data. Based on a combined partial beta-tubulin (BenA), calmodulin
(CaM) and RNA polymerase II second largest subunit (RPB2) multigene sequence
dataset, we introduce two new sections (Osmophila and Robsamsonia) in subgenus
Penicillium and synonymize section Digitata with section Penicillium. The
phylogeny correlates well with phenotypic, physiological and ecological data, and
some extrolites were diagnostic for certain Penicillium sections. Furthermore,
four new species belonging to the newly introduced sections are described using a
polyphasic approach, including BenA, CaM and RPB2 sequences, macro- and
micromorphological data and extrolite profiles. The new section Robsamsonia and
the new species Penicillium robsamsonii and Penicillium samsonianum were
introduced to celebrate Dr. Robert A. Samson's 70th birthday.
PMID- 27616796
TI - Robert A. Samson - CBS-KNAW Fungal Biodiversity Centre.
PMID- 27616797
TI - Economic Growth Evens Out Happiness: Evidence from Six Surveys.
AB - In spite of the great U-turn that saw income inequality rise in Western countries
in the 1980s, happiness inequality has fallen in countries that have experienced
income growth (but not in those that did not). Modern growth has reduced the
share of both the "very unhappy" and the "perfectly happy". Lower happiness
inequality is found both between and within countries, and between and within
individuals. Our cross-country regression results argue that the extension of
various public goods helps to explain this greater happiness homogeneity. This
new stylised fact arguably comes as a bonus to the Easterlin paradox, offering a
somewhat brighter perspective for developing countries.
PMID- 27616798
TI - DEMOGRAPHIC OPPORTUNITY AND THE MATE SELECTION PROCESS IN INDIA.
AB - We merged individual-level data from the 2004-2005 India Human Development Survey
with district-level data derived from the 1991 and 2001 Indian population
censuses to examine how the numerical supply of men to which married women were
exposed during late adolescence is associated with women's agency in the mate
selection process and the duration of courtships. Multilevel models that control
for an array of both individual and contextual factors showed that exposure to a
relative surplus of potential mates is associated with a higher likelihood that
women will have little or no say in the selection of their husband and an
increased probability that women will meet their husband for the first time on
their wedding day. Women's educational attainment, birth cohort, religion, caste,
and region of residence also emerged as significant correlates of women's marital
agency and courtship duration. The implications of these findings for India's
growing sex ratio imbalance are discussed.
PMID- 27616799
TI - Effects of a natural extract of Aronia Melanocarpa berry on endothelial cell
nitric oxide production.
AB - : The effects of acute and chronic treatment with Aronia extracts on NO
production and endothelial nitric oxide synthase (eNOS) phosphorylation in bovine
coronary artery endothelial cells were investigated. Acute time-course and
concentration-response experiments were performed to determine the time and
concentration at which Aronia induced maximal NO synthesis and eNOS
phosphorylation. The findings indicate that relatively low concentrations (0.1
MUg/mL) of Aronia extract significantly induced NO synthesis and eNOS
phosphorylation after 10 min of treatment. Increased sensitivity of eNOS and a
significant increase in NO synthesis resulted from longer-term stimulation with
Aronia (48 hr) and an acute re-treatment of the cells (10 min). PRACTICAL
APPLICATIONS: These in vitro results may be translated into potential future
clinical applications where Aronia extracts may be used for prevention and
coadjuvant treatment of cardiovascular diseases via increases in endothelial NO
synthesis and related improvements in vascular functions. Given the dose-response
effect of Aronia extract in vitro and metabolism of polyphenols that occurs in
humans, dose-response studies would be necessary to define the optimal daily
amount to be consumed.
PMID- 27616800
TI - Impulsivity, Rejection Sensitivity, and Reactions to Stressors in Borderline
Personality Disorder.
AB - This research investigated baseline impulsivity, rejection sensitivity, and
reactions to stressors in individuals with borderline personality disorder
compared to healthy individuals and those with avoidant personality disorder. The
borderline group showed greater impulsivity than the avoidant and healthy groups
both in a delay-discounting task with real monetary rewards and in self-reported
reactions to stressors; moreover, these findings could not be explained by co
occurring substance use disorders. Distress reactions to stressors were equally
elevated in both personality disorder groups (relative to the healthy group). The
borderline and avoidant groups also reported more maladaptive reactions to a
stressor of an interpersonal vs. non-interpersonal nature, whereas the healthy
group did not. Finally, self-reported impulsive reactions to stressors were
associated with baseline impulsivity in the delay-discounting task, and greater
self-reported reactivity to interpersonal than non-interpersonal stressors was
associated with rejection sensitivity. This research highlights distinct
vulnerabilities contributing to impulsive behavior in borderline personality
disorder.
PMID- 27616795
TI - Fungal Planet description sheets: 400-468.
AB - Novel species of fungi described in the present study include the following from
Australia: Vermiculariopsiella eucalypti, Mulderomyces natalis (incl.
Mulderomyces gen. nov.), Fusicladium paraamoenum, Neotrimmatostroma
paraexcentricum, and Pseudophloeospora eucalyptorum on leaves of Eucalyptus spp.,
Anungitea grevilleae (on leaves of Grevillea sp.), Pyrenochaeta acaciae (on
leaves of Acacia sp.), and Brunneocarpos banksiae (incl. Brunneocarpos gen. nov.)
on cones of Banksia attenuata. Novel foliicolous taxa from South Africa include
Neosulcatispora strelitziae (on Strelitzia nicolai), Colletotrichum ledebouriae
(on Ledebouria floridunda), Cylindrosympodioides brabejum (incl.
Cylindrosympodioides gen. nov.) on Brabejum stellatifolium, Sclerostagonospora
ericae (on Erica sp.), Setophoma cyperi (on Cyperus sphaerocephala), and
Phaeosphaeria breonadiae (on Breonadia microcephala). Novelties described from
Robben Island (South Africa) include Wojnowiciella cissampeli and Diaporthe
cissampeli (both on Cissampelos capensis), Phaeotheca salicorniae (on Salicornia
meyeriana), Paracylindrocarpon aloicola (incl. Paracylindrocarpon gen. nov.) on
Aloe sp., and Libertasomyces myopori (incl. Libertasomyces gen. nov.) on Myoporum
serratum. Several novelties are recorded from La Reunion (France), namely
Phaeosphaeriopsis agapanthi (on Agapanthus sp.), Roussoella solani (on Solanum
mauritianum), Vermiculariopsiella acaciae (on Acacia heterophylla), Dothiorella
acacicola (on Acacia mearnsii), Chalara clidemiae (on Clidemia hirta), Cytospora
tibouchinae (on Tibouchina semidecandra), Diaporthe ocoteae (on Ocotea obtusata),
Castanediella eucalypticola, Phaeophleospora eucalypticola and Fusicladium
eucalypticola (on Eucalyptus robusta), Lareunionomyces syzygii (incl.
Lareunionomyces gen. nov.) and Parawiesneriomyces syzygii (incl.
Parawiesneriomyces gen. nov.) on leaves of Syzygium jambos. Novel taxa from the
USA include Meristemomyces arctostaphylos (on Arctostaphylos patula), Ochroconis
dracaenae (on Dracaena reflexa), Rasamsonia columbiensis (air of a hotel
conference room), Paecilomyces tabacinus (on Nicotiana tabacum),
Toxicocladosporium hominis (from human broncoalveolar lavage fluid), Nothophoma
macrospora (from respiratory secretion of a patient with pneumonia), and
Penidiellopsis radicularis (incl. Penidiellopsis gen. nov.) from a human nail.
Novel taxa described from Malaysia include Prosopidicola albizziae (on Albizzia
falcataria), Proxipyricularia asari (on Asarum sp.), Diaporthe passifloricola (on
Passiflora foetida), Paramycoleptodiscus albizziae (incl. Paramycoleptodiscus
gen. nov.) on Albizzia falcataria, and Malaysiasca phaii (incl. Malaysiasca gen.
nov.) on Phaius reflexipetalus. Two species are newly described from human
patients in the Czech Republic, namely Microascus longicollis (from toenails of
patient with suspected onychomycosis), and Chrysosporium echinulatum (from sole
skin of patient). Furthermore, Alternaria quercicola is described on leaves of
Quercus brantii (Iran), Stemphylium beticola on leaves of Beta vulgaris (The
Netherlands), Scleroderma capeverdeanum on soil (Cape Verde Islands), Scleroderma
dunensis on soil, and Blastobotrys meliponae from bee honey (Brazil), Ganoderma
mbrekobenum on angiosperms (Ghana), Geoglossum raitviirii and Entoloma
kruticianum on soil (Russia), Priceomyces vitoshaensis on Pterostichus melas
(Carabidae) (Bulgaria) is the only one for which the family is listed, Ganoderma
ecuadoriense on decaying wood (Ecuador), Thyrostroma cornicola on Cornus
officinalis (Korea), Cercophora vinosa on decorticated branch of Salix sp.
(France), Coprinus pinetorum, Coprinus littoralis and Xerocomellus poederi on
soil (Spain). Two new genera from Colombia include Helminthosporiella and
Uwemyces on leaves of Elaeis oleifera. Two species are described from India,
namely Russula intervenosa (ectomycorrhizal with Shorea robusta), and Crinipellis
odorata (on bark of Mytragyna parviflora). Novelties from Thailand include
Cyphellophora gamsii (on leaf litter), Pisolithus aureosericeus and Corynascus
citrinus (on soil). Two species are newly described from Citrus in Italy, namely
Dendryphiella paravinosa on Citrus sinensis, and Ramularia citricola on Citrus
floridana. Morphological and culture characteristics along with ITS nrDNA
barcodes are provided for all taxa.
PMID- 27616801
TI - Fast, Exact Bootstrap Principal Component Analysis for p > 1 million.
AB - Many have suggested a bootstrap procedure for estimating the sampling variability
of principal component analysis (PCA) results. However, when the number of
measurements per subject (p) is much larger than the number of subjects (n),
calculating and storing the leading principal components from each bootstrap
sample can be computationally infeasible. To address this, we outline methods for
fast, exact calculation of bootstrap principal components, eigenvalues, and
scores. Our methods leverage the fact that all bootstrap samples occupy the same
n-dimensional subspace as the original sample. As a result, all bootstrap
principal components are limited to the same n-dimensional subspace and can be
efficiently represented by their low dimensional coordinates in that subspace.
Several uncertainty metrics can be computed solely based on the bootstrap
distribution of these low dimensional coordinates, without calculating or storing
the p-dimensional bootstrap components. Fast bootstrap PCA is applied to a
dataset of sleep electroencephalogram recordings (p = 900, n = 392), and to a
dataset of brain magnetic resonance images (MRIs) (p ~ 3 million, n = 352). For
the MRI dataset, our method allows for standard errors for the first 3 principal
components based on 1000 bootstrap samples to be calculated on a standard laptop
in 47 minutes, as opposed to approximately 4 days with standard methods.
PMID- 27616802
TI - The divorce of Sporothrix and Ophiostoma: solution to a problematic relationship.
AB - One of the causal agents of human sporotrichosis, Sporothrix schenckii, is the
type species of the genus Sporothrix. During the course of the last century the
asexual morphs of many Ophiostoma spp. have also been treated in Sporothrix. More
recently several DNA-based studies have suggested that species of Sporothrix and
Ophiostoma converge in what has become known as Ophiostoma s. lat. Were the one
fungus one name principles adopted in the Melbourne Code to be applied to
Ophiostoma s. lat., Sporothrix would have priority over Ophiostoma, resulting in
more than 100 new combinations. The consequence would be name changes for several
economically important tree pathogens including O. novo-ulmi. Alternatively,
Ophiostoma could be conserved against Sporothrix, but this would necessitate
changing the names of the important human pathogens in the group. In this study,
we sought to resolve the phylogenetic relationship between Ophiostoma and
Sporothrix. DNA sequences were determined for the ribosomal large subunit and
internal transcribed spacer regions, as well as the beta-tubulin and calmodulin
genes in 65 isolates. The results revealed Sporothrix as a well-supported
monophyletic lineage including 51 taxa, distinct from Ophiostoma s. str. To
facilitate future studies exploring species level resolution within Sporothrix,
we defined six species complexes in the genus. These include the Pathogenic Clade
containing the four human pathogens, together with the S. pallida-, S. candida-,
S. inflata-, S. gossypina- and S. stenoceras complexes, which include
environmental species mostly from soil, hardwoods and Protea infructescences. The
description of Sporothrix is emended to include sexual morphs, and 26 new
combinations. Two new names are also provided for species previously treated as
Ophiostoma.
PMID- 27616804
TI - Parenting Stress among Low-Income and Working-Class Fathers: The Role of
Employment.
AB - Contemporary norms of fatherhood emphasize the dual demands of breadwinning and
daily involvement in childcare. Recent qualitative research suggests that working
class fathers find it difficult to meet these demands due to job instability and
workplace inflexibility. Yet, little quantitative research has examined how
employment characteristics are related to fathers' parenting stress, in
comparison with mothers'. Analyses using data from the Fragile Families and Child
Wellbeing Study (N = 3,165) show that unemployment and workplace inflexibility,
but not overwork, multiple jobs, odd-jobs, and nonstandard hours, are related to
more parenting stress for fathers. Although these two factors are also related to
more parenting stress for mothers, nuanced gender differences emerged: these are
better predictors than other parental or child characteristics for fathers only,
and the effect size of workplace inflexibility is greater for fathers than
mothers. In sum, securing a job with flexible schedule is central to reducing
fathers' parenting stress.
PMID- 27616803
TI - Phylogeny and taxonomic revision of Microascaceae with emphasis on synnematous
fungi.
AB - The taxonomy of the synnematous genera Cephalotrichum, Doratomyces and Trichurus,
and other related genera Gamsia, Wardomyces and Wardomycopsis, has been
controversial and relies mainly on morphological criteria. These are
microascaceous saprobic fungi mostly found in air and soil and with a worldwide
distribution. In order to clarify their taxonomy and to delineate generic
boundaries within the Microascaceae, we studied 57 isolates that include
clinical, environmental and all the available ex-type strains of a large set of
species by means of morphological, physiological and molecular phylogenetic
analyses using DNA sequence data of four loci (the ITS region, and fragments of
rDNA LSU, translation elongation factor 1alpha and beta-tubulin). The results
demonstrate that Cephalotrichum, Doratomyces and Trichurus are congeneric and the
genus Cephalotrichum is accepted here with Echinobotryum as a further synonym.
The genera Acaulium and Fairmania, typified by A. albonigrescens and F.
singularis, respectively, are distinct from Microascus and Scopulariopsis, Gamsia
is distinct from Wardomyces, and Wardomycopsis is confirmed as a separate genus
in the Microascaceae. Two new species of Cephalotrichum are described as C.
brevistipitatum and C. hinnuleum. Nine new combinations are proposed, i.e.
Acaulium acremonium, A. caviariforme, Cephalotrichum asperulum, C. columnare, C.
cylindricum, C. dendrocephalum, C. gorgonifer, Gamsia columbina and Wardomyces
giganteus. A neotype is designed for C. stemonitis. Lectotypes and epitypes are
designated for A. acremonium, A. albonigrescens, C. gorgonifer, C. nanum and W.
anomalus. Cephalotrichum cylindricum, C. microsporum, F. singularis and Gamsia
columbina are also epitypified with new specimens. Descriptions of the phenotypic
features and dichotomous keys for identification are provided for accepted
species in the different genera.
PMID- 27616806
TI - Where do Property Rights Matter More? Explaining the Variation in Demand for
Property Titles across Cities in Mexico.
AB - This paper examines the variation in the value of property rights to housing in
Mexico, focusing specifically on differences between urban housing markets.
Roughly 30% of owner-occupied houses in Mexico do not have a proper deed. Houses
with no deed are estimated to be five percent less valuable than otherwise
similar houses with a full deed, yet this premium varies widely across cities. I
match data from the 2012 and 2014 National Survey of Household Incomes and
Expenditures to different sources of city-level data in order to examine
hypotheses explaining this variation in a multilevel regression framework. I find
that deeds are valued more in cities with more highly educated residents, more
political competition, and more voting. Measures of local economic activity,
degree of informality, and the regulatory bureaucracy are not associated with
higher value to full property rights. Additionally, I find that more educated
households value deeds more, and having a deed is more valuable for larger houses
in neighborhoods with less vacancy and higher infrastructure quality. Based on
these results, I suggest funds to subsidize titling should be redirected to
places where titles are worth more. More broadly, I suggest policymakers
reconsider framing property-titling programs as poverty alleviation. Low-income
households would benefit more from subsidies for improvements to housing and
residential infrastructure. At the same time, the federal government should
further push to reduce the costs of transferring property.
PMID- 27616807
TI - Evaluating susceptibility of karst dolines (sinkholes) for collapse in Sango,
Tennessee, USA.
AB - Dolines or sinkholes are earth depressions that develop in soluble rocks
complexes such as limestone, dolomite, gypsum, anhydrite, and halite; dolines
appear in a variety of shapes from nearly circular to complex structures with
highly curved perimeters. The occurrence of dolines in the studied karst area is
not random; they are the results of geomorphic, hydrologic, and chemical
processes that have caused partial subsidence, even the total collapse of the
land surface when voids and caves are present in the bedrock and the regolith
arch overbridging these voids is unstable. In the study area, the majority of
collapses occur in the regolith (bedrock cover) that bridges voids in the
bedrock. Because these collapsing dolines may result in property damage and even
cause the loss of lives, there is a need to develop methods for evaluating karst
hazards. These methods can then be used by planners and practitioners for urban
and economic development, especially in regions with a growing population. The
purpose of this project is threefold: 1) to develop a karst feature database, 2)
to investigate critical indicators associated with doline collapse, and 3) to
develop a doline susceptibility model for potential doline collapse based on
external morphometric data. The study has revealed the presence of short range
spatial dependence in the distribution of the dolines' morphometric parameters
such as circularity, the geographic orientation of the main doline axes, and the
length-to-width doline ratios; therefore, geostatistics can be used to spatially
evaluate the susceptibility of the karst area for doline collapse. The partial
susceptibility estimates were combined into a final probability map enabling the
identification of areas where, until now, undetected dolines may cause
significant hazards.
PMID- 27616805
TI - Parenting and Preschool Self-Regulation as Predictors of Social Emotional
Competence in 1st Grade.
AB - The current longitudinal study used data from the National Institute of Child
Health and Human Development (NICHD) Study of Early Child Care and Youth
Development (SECCYD) to examine a model of development that emphasizes early
caregiving environments as predictors of social emotional competence (including
classroom competence). This path analysis model included features of parenting,
emotion regulation, preschool language skills, and attention to predict child
outcomes in 1st grade. Early caregiving environments were directly predictive of
peer relationship satisfaction, oppositional behavior, social skills, and
classroom competence over and above significant mediated effects through
preschool self regulation (language, inattention, and anger/frustration). These
results suggest that the characteristics of supportive and stimulating caregiving
shift in valence over time, such that qualities of the infant-child relationship
that are significant in predicting early childhood outcomes are not the same as
the caregiving qualities that move to the foreground in predicting primary school
outcomes. Implications for school-readiness programming are discussed, including
interventions in the early caregiving system to encourage sensitive and
supportive parent child interactions to bolster school readiness via the
development of social-emotional competence.
PMID- 27616808
TI - Sigma virus and male reproductive success in Drosophila melanogaster.
AB - The risk of disease transmission can affect female mating rate, and thus sexual
conflict. Furthermore, the interests of a sexually transmitted organism may align
or diverge with those of either sex, potentially making the disease agent a third
participant in the sexual arms race. In Drosophila melanogaster, where sexual
conflict over female mating rate is well established, we investigated how a
common, non-lethal virus (sigma virus) might affect this conflict. We gave
uninfected females the opportunity to copulate twice in no-choice trials: either
with two uninfected males, or with one male infected with sigma virus followed by
an uninfected male. We assessed whether females respond behaviorally to male
infection, determined whether male infection affects either female or male
reproductive success, and measured offspring infection rates. Male infection
status did not influence time to copulation, or time to re-mating. However, male
infection did affect male reproductive success: first males sired a significantly
greater proportion of offspring, as well as more total offspring, when they were
infected with sigma virus. Thus viral infection may provide males an advantage in
sperm competition, or, possibly, females may preferentially use infected sperm.
We found no clear costs of infection in terms of offspring survival. Viral
reproductive success (the number of infected offspring) was strongly correlated
with male reproductive success. Further studies are needed to demonstrate whether
virus-induced changes in reproductive success affect male and female lifetime
fitness, and whether virus-induced changes are under male, female, or viral
control.
PMID- 27616809
TI - Ant larvae regulate worker foraging behavior and ovarian activity in a dose
dependent manner.
AB - Division of labor in insect societies relies on simple behavioral rules, whereby
individual colony members respond to dynamic signals indicating the need for
certain tasks to be performed. This in turn gives rise to colony-level
phenotypes. However, empirical studies quantifying colony-level signal-response
dynamics are lacking. Here, we make use of the unusual biology and experimental
amenability of the queenless clonal raider ant Cerapachys biroi, to jointly
quantify the behavioral and physiological responses of workers to a social signal
emitted by larvae. Using automated behavioral quantification and oocyte size
measurements in colonies of different sizes and with different worker to larvae
ratios, we show that the workers in a colony respond to larvae by increasing
foraging activity and inhibiting ovarian activation in a progressive manner, and
that these responses are stronger in smaller colonies. This work adds to our
knowledge of the processes that link plastic individual behavioral/physiological
responses to colony-level phenotypes in social insect colonies.
PMID- 27616810
TI - Evaluation of an electrostatic particle ionization technology for decreasing
airborne pathogens in pigs.
AB - Influenza A virus (IAV), porcine reproductive and respiratory syndrome virus
(PRRSV), porcine epidemic diarrhea virus (PEDV) and Staphylococcus aureus are
important swine pathogens capable of being transmitted via aerosols. The
electrostatic particle ionization system (EPI) consists of a conductive line that
emits negative ions that charge particles electrically resulting in the settling
of airborne particles onto surfaces and potentially decreasing the risk of
pathogen dissemination. The objectives of this study were to determine the effect
of the EPI system on the quantity and viability of IAV, PRRSV, PEDV and S. aureus
in experimentally generated aerosols and in aerosols generated by infected
animals. Efficiency at removing airborne particles was evaluated as a function of
particle size (ranging from 0.4 to 10 um), distance from the source of ions (1, 2
and 3 m) and relative air humidity (RH 30 vs. 70 %). Aerosols were sampled with
the EPI system "off" and "on." Removal efficiency was significantly greater for
all pathogens when the EPI line was the closest to the source of aerosols. There
was a greater reduction for larger particles ranging between 3.3 and 9 um, which
varied by pathogen. Overall airborne pathogen reduction ranged between 0.5 and
1.9 logs. Viable pathogens were detected with the EPI system "on," but there was
a trend to reducing the quantity of viable PRRSV and IAV. There was not a
significant effect on the pathogens removal efficiency based on the RH conditions
tested. In summary, distance to the source of ions, type of pathogen and particle
size influenced the removal efficiency of the EPI system. The reduction in
infectious agents in the air by the EPI technology could potentially decrease the
microbial exposure for pigs and people in confinement livestock facilities.
PMID- 27616811
TI - Forecasting model of Corylus, Alnus, and Betula pollen concentration levels using
spatiotemporal correlation properties of pollen count.
AB - The aim of the study was to create and evaluate models for predicting high levels
of daily pollen concentration of Corylus, Alnus, and Betula using a
spatiotemporal correlation of pollen count. For each taxon, a high pollen count
level was established according to the first allergy symptoms during exposure.
The dataset was divided into a training set and a test set, using a stratified
random split. For each taxon and city, the model was built using a random forest
method. Corylus models performed poorly. However, the study revealed the
possibility of predicting with substantial accuracy the occurrence of days with
high pollen concentrations of Alnus and Betula using past pollen count data from
monitoring sites. These results can be used for building (1) simpler models,
which require data only from aerobiological monitoring sites, and (2) combined
meteorological and aerobiological models for predicting high levels of pollen
concentration.
PMID- 27616812
TI - Cat (Fel d 1) and dog (Can f 1) allergen levels in cars, dwellings and schools.
AB - Pets are an important source of indoor allergens. The aim of the study was to
compare cat and dog allergen levels in cars, schools and homes. The study was
carried out in 17 cars, 14 classrooms and 19 dwellings located in the highly
industrialized and urbanized region of Poland. Dust and air samples were analyzed
for Fel d 1 and Can f 1 using a double monoclonal ELISA assay. The highest
amounts of cat and dog allergens (Fel d 1: 1169 MUg/g; Can f 1: 277 MUg/g) were
found in dwellings with pets. Allergen concentrations were correlated with the
number of animals kept at home. Although concentrations on automobile seats were
lower, Fel d 1 levels exceeded 8 MUg/g in 23.5 % of cars and high levels of Can f
1 (>10 MUg/g) were found in 17.6 % of cars. The study revealed that cars of pet
owners may be reservoirs of cat and dog allergens even when animals are not
transported in them. In schools, concentrations of pet allergens did not reach
high levels, but the moderate levels of Fel d 1 (>=1-8 MUg/g) and Can f 1 (>=2-10
MUg/g) were detected in 42.9 and 7.1 % of the investigated classrooms.
Concentrations of cat and dog allergen in schools were higher than in homes
without pets. While airborne Fel d 1 and Can f 1 levels were found low,
residential allergen concentrations in settled dust and air were correlated. The
study results suggest that classrooms and cars of pet owners may be important
sites of exposure to cat and dog allergens, though the highest concentrations of
Fel d 1 and Can f 1 are found in homes of pet owners.
PMID- 27616813
TI - School Segregation, Charter Schools, and Access to Quality Education.
AB - Race, class, neighborhood, and school quality are all highly inter-related in the
American educational system. In the last decade a new factor has come into play,
the option of attending a charter school. We offer a comprehensive analysis of
the disparities among public schools attended by white, black, Hispanic, Asian,
and Native American children in 2010-2011, including all districts in which
charter schools existed. We compare schools in terms of poverty concentration,
racial composition, and standardized test scores, and we also examine how
attending a charter or non-charter school affects these differences. Black and
Hispanic (and to a lesser extent Native American and Asian) students attend
elementary and high schools with higher rates of poverty than white students.
Especially for whites and Asians, attending a charter school means lower exposure
to poverty. Children's own race and the poverty and charter status of their
schools affect the test scores and racial isolation of schools that children
attend in complex combinations. Most intriguing, attending a charter school means
attending a better performing school in high-poverty areas but a lower performing
school in low-poverty areas. Yet even in the best case the positive effect of
attending a charter school only slightly offsets the disadvantages of black and
Hispanic students.
PMID- 27616814
TI - Examining the Consequences of the "Prevalent Life Events" of Arrest and
Incarceration among an Urban African-American Cohort.
AB - The life course perspective has traditionally examined prevalent adult life
events, such as marriage and employment, and their potential to redirect
offending trajectories. However, for African Americans, the life events of arrest
and incarceration are becoming equally prevalent in young adulthood. Therefore,
it is critical to understand how these "standard" criminal justice practices,
which are designed to deter as well as punish, affect deviance among this
population. This study evaluates the long-term consequences of criminal justice
intervention on substance use and offending into midlife among an African
American community cohort using propensity score matching and multivariate
regression analyses. The results largely point to a criminogenic effect of
criminal justice intervention on midlife deviance with a particularly strong
effect of young adult arrest on rates of violent and property arrest counts into
midlife. The theoretical and policy implications of the findings are discussed.
PMID- 27616815
TI - TOWARD A CRIMINOLOGY OF INMATE NETWORKS.
AB - The mid-twentieth century witnessed a surge of American prison ethnographies
focused on inmate society and the social structures that guide inmate life.
Ironically, this literature virtually froze in the 1980s just as the country
entered a period of unprecedented prison expansion, and has only recently begun
to thaw. In this manuscript, we develop a rationale for returning inmate society
to the forefront of criminological inquiry, and suggest that network science
provides an ideal framework for achieving this end. In so doing, we show that a
network perspective extends prison ethnographies by allowing quantitative
assessment of prison culture and illuminating basic characteristics of prison
social structure that are essential for improving inmate safety, health, and
community reentry outcomes. We conclude by demonstrating the feasibility and
promise of inmate network research with findings from a recent small-scale study
of a maximum-security prison work unit.
PMID- 27616816
TI - Well-controlled ATRP of 2-(2-(2-Azidoethyoxy)ethoxy)ethyl Methacrylate for High
density Click Functionalization of Polymers and Metallic Substrates.
AB - The combination of atom transfer radical polymerization (ATRP) and click
chemistry has created unprecedented opportunities for controlled syntheses of
functional polymers. ATRP of azido-bearing methacrylate monomers (e.g. 2-(2-(2
azidoethyoxy)ethoxy)ethyl methacrylate, AzTEGMA), however, proceeded with poor
control at commonly adopted temperature of 50 degrees C, resulting in
significant side reactions. By lowering reaction temperature and monomer
concentrations, well-defined pAzTEGMA with significantly reduced polydispersity
were prepared within a reasonable timeframe. Upon subsequent functionalization of
the side chains of pAzTEGMA via Cu(I)-catalyzed azide-alkyne cycloaddition
(CuAAC) click chemistry, functional polymers with number-average molecular
weights (Mn) up to 22 kDa with narrow polydispersity (PDI < 1.30) were obtained.
Applying the optimized polymerization condition, we also grafted pAzTEGMA brushes
from Ti6Al4 substrates by surface-initiated ATRP (SI-ATRP), and effectively
functionalized the azide-terminated side chains with hydrophobic and hydrophilic
alkynes by CuAAC. The well-controlled ATRP of azido-bearing methacrylates and
subsequent facile high-density functionalization of the side chains of the
polymethacrylates via CuAAC offers a useful tool for engineering functional
polymers or surfaces for diverse applications.
PMID- 27616817
TI - Sandwiches and subversion: Teachers' mealtime strategies and preschoolers'
agency.
AB - Mealtimes are understudied processes in the social research on childhood. Our
study uses ethnographic methods in two preschools in the southeastern United
States to understand the types of strategies teachers use during meals and
children's responses to these strategies. We identified three strategies teachers
used to attempt to modify children's consumption: gatekeeping, directives, and
hyperbolic justifications of consumption. We argue that children used agency to
subvert to teachers' strategies using silent and verbal techniques, including
attempting to open packages of restricted foods, pretending to eat, and refusing
to eat. Their subversion manifested in either "dissent" or "feigned assent."
PMID- 27616818
TI - Gender, Educational Attainment, and the Impact of Parental Migration on Children
Left Behind.
AB - Estimation of the causal effect of parental migration on children's educational
attainment is complicated by the fact that migrants and non-migrants are likely
to differ in unobservable ways that also affect children's educational outcomes.
This paper suggests a novel way of addressing this selection problem by looking
within the family to exploit variation in siblings' ages at the time of parental
migration. The basic assumption underlying the analysis is that parental
migration will have no effect on the educational outcomes of children who are at
least 20 because they have already completed their educations. Their younger
siblings, in contrast, may still be in school, and thus will be affected by the
parental migration experience. The results point to a statistically significant
positive effect of paternal U.S. migration on education for girls, suggesting
that pushing a father's U.S. migration earlier in his daughter's life can lead to
an increase in her educational attainment of up to 1 year relative to delaying
migration until after she has turned 20. In contrast, paternal domestic migration
has no statistically significant effect on educational attainment for girls or
boys, suggesting that father absence does not play a major role in determining
children's educational outcomes. Instead, these results suggest that the marginal
dollars from U.S. migrant remittances appear to enable families to further
educate their daughters. Thus, policymakers should view international migration
as a potential pathway by which families raise educational attainments of girls
in particular. JEL: O15; J12; J13; J16; J24; F22.
PMID- 27616819
TI - A CMAC-based scheme for determining membership with classification of text
strings.
AB - Membership determination of text strings has been an important procedure for
analyzing textual data of a tremendous amount, especially when time is a crucial
factor. Bloom filter has been a well-known approach for dealing with such a
problem because of its succinct structure and simple determination procedure. As
determination of membership with classification is becoming increasingly
desirable, parallel Bloom filters are often implemented for facilitating the
additional classification requirement. The parallel Bloom filters, however, tend
to produce additional false-positive errors since membership determination must
be performed on each of the parallel layers. We propose a scheme based on CMAC, a
neural network mapping, which only requires a single-layer calculation to
simultaneously obtain information of both the membership and classification. A
hash function specifically designed for text strings is also proposed. The
proposed scheme could effectively reduce false-positive errors by converging the
range of membership acceptance to the minimum for each class during the neural
network mapping. Simulation results show that the proposed scheme committed
significantly less errors than the benchmark, parallel Bloom filters, with
limited and identical memory usage at different classification levels.
PMID- 27616820
TI - Health, SES, and the Timing of Education Among Military Retirees.
AB - The timing of education across the life cycle is differentially associated with
older-age health outcomes and socioeconomic status among military retirees, a
subpopulation with common levels of adolescent health but variation in
educational timing. A year of education obtained before military service lowers
the probability of poor health in retirement by 2.5 percentage points, while a
year obtained after service reduces poor health by only 0.6 percentage point. By
contrast, education raises income and wealth uniformly through vintage. This
suggests that education improves health through fostering the lifelong
accumulation of healthy behaviors and habits rather than raising income or
wealth.
PMID- 27616822
TI - Clinical Outcome of Metacarpophalangeal Joint Dislocation of the Thumb in
Children: Case Series of 10 Patients.
AB - OBJECTIVES: Dislocation of the metacarpophalangeal joint of the thumb in children
is an uncommon entity. The aim of this study was to evaluate the clinical outcome
of pediatric patients with metacarpophalangeal joint dislocation of the thumb.
PATIENTS AND METHODS: Ten pediatric patients with metacarpophalangeal joint
dislocation of the thumb were evaluated. Patients were studied prospectively over
a period of 3 years. Parameters studied included patient demographics, type of
dislocation, management, and any complications. RESULTS: Mean age of patients was
6.8 years (range: 3-12 years). Seven patients underwent closed reduction and
three patients were managed by open reduction. Of the total 10 patients,
excellent results were obtained in 9 patients. One of the patients who reported
on the fourth day of trauma and was managed by open reduction had mild joint
stiffness with a range of motion of 10 to 40 degrees at final follow-up. None of
these patients had infection or instability. CONCLUSION: After thorough clinical
and radiological examination, closed reduction can be done in incomplete and
simple complete dislocations of metacarpophalangeal joint of the thumb. Repeated
closed reduction should be avoided in complex complete injuries. Early
mobilization is advised to prevent joint stiffness.
PMID- 27616821
TI - Traumatic Extensor Tendon Injuries to the Hand: Clinical Anatomy, Biomechanics,
and Surgical Procedure Review.
AB - The extensor apparatus is a complex muscle-tendon system that requires integrity
or optimal reconstruction to preserve hand function. Anatomical knowledge and the
understanding of physiopathology of extensor tendons are essential for an
accurate diagnosis of extensor tendon injuries (ETIs) of the hand and wrist,
because these lesions are complex and commonly observed in clinical practice. A
careful clinical history and assessment still remain the first step for the
diagnosis, followed by US and MR to confirm the suspect of ETI or to investigate
some doubtful conditions and rule out associate lesions. During last decades the
evolution of surgical techniques and rehabilitative treatment protocol led to
gradual improvement in clinical results of ETI treatment and surgical repair.
Injury classification into anatomical zones and the evaluation of the
characteristics of the lesions are considered key points to select the
appropriate treatment for ETI. Both conservative and surgical management can be
indicated in ETI, depending on the anatomical zone and on the characteristics of
the injuries. As a general rule, an attempt of conservative treatment should be
performed when the lesion is expected to have favorable result with nonoperative
procedure. Many surgical techniques have been proposed over the time and with
favorable results if the tendon injury is not underestimated and adequately
treated. Despite recent research findings, a lack of evidence-based knowledge is
still observed in surgical treatment and postoperative management of ETI. Further
clinical and biomechanical investigations would be advisable to clarify this
complex issue.
PMID- 27616823
TI - A Novel Perforator Flap Training Model Using a Chicken Leg.
AB - INTRODUCTION: Living animal models are frequently used for perforator flap
dissection training, but no ex vivo models have been described. The aim of this
study is to present a novel nonliving model for perforator flap training based on
a constant perforator in the chicken leg. METHODS: A total of 15 chicken legs
were used in this study. Anatomical dissection of the perforator was performed
after its identification using ink injection, and in four of these specimens a
perforator-based flap was raised. RESULTS: The anatomical dissection revealed a
constant intramuscular perforator with a median length of 5.7 cm. Median proximal
and distal vessel diameters were 0.93 and 0.4 mm, respectively. The median
dissection time was 77.5 minutes. CONCLUSION: This study introduces a novel,
affordable, and reproducible model for the intramuscular dissection of a
perforator-based flap using an ex vivo animal model. Its consistent perforator
and appropriate-sized vessels make it useful for training.
PMID- 27616825
TI - Role of Guided Ultrasound in the Treatment of De Quervain Tenosynovitis by Local
Steroid Infiltration.
AB - Ultrasound guidance for steroid injection in de Quervain disease is useful in
identifying the presence of subcompartments and effectively injecting the drug
into tendon sheath. We prospectively studied 50 patients with features of de
Quervain disease to determine the effectiveness of ultrasound in positioning of
needle for steroid injection and effectiveness of single versus multiple
injections in the presence of subcompartments. Scalp vein set was inserted into
the tendon sheath under ultrasound guidance and sterile conditions. Mixture
containing 1 mL of methylprednisolone 40 mg with 1 mL of 2% lignocaine was
injected and the patient followed for 6 months. In patients having
subcompartments, improvement was better when two separate injections into each
subcompartment were given compared with single. Ultrasound guidance is helpful in
identifying the existence of subcompartment and injecting the subcompartments
separately. Scalp vein set may be very effective in ultrasound-guided injection.
This is a level III study.
PMID- 27616824
TI - Carpal Tunnel Injections: A Novel Approach Based on Wrist Width.
AB - INTRODUCTION: Carpal tunnel steroid injections (CTIs) have the potential risk of
damaging underlying critical structures, including the median nerve (MN), radial
artery (RA), and ulnar neurovascular bundle (UB). The purpose of this study was
to analyze the safety of a volar radial (VR) and volar ulnar (VU) CTI, using
standardized anatomical "safe zones." MATERIALS AND METHODS: This study was
performed on 87 cadaveric arms using a percentage of the total wrist width as a
guide for placement of a VR (30 and 33% of total wrist width) and VU (60 and 66%
of total wrist width) injection. RESULTS: Our results demonstrate a wide range of
anatomic variations in the location of these critical neurovascular structures
near the carpal canal, indicating that using superficial landmarks alone for CTIs
may result in an increased risk of iatrogenic injury to these critical
structures. DISCUSSION: We propose a technique using a percentage of total wrist
width as a guide for CTIs. Both VR (30% of wrist width) and VU (60% of wrist
width) CTIs offer relatively safe and reliable CTI locations to the carpal canal.
LEVEL OF EVIDENCE: Not applicable/cadaveric study.
PMID- 27616826
TI - Autogenous Vein Wrapping versus In Situ Decompression for Management of Secondary
Cubital Tunnel Syndrome after Surgical Fixation of Elbow Fractures: Short-Term
Functional and Neurophysiological Outcome.
AB - PURPOSE: The aim of this study was to compare the functional and
neurophysiological outcome of in situ decompression versus in situ decompression
augmented with autogenous vein wrapping in management of secondary cubital tunnel
syndrome at the elbow following fixation of elbow fractures. METHODS: A
prospective comparative randomized study was performed on 29 patients who were
divided into two groups: group I (in situ decompression) and group II (in situ
decompression augmented with autogenous vein wrapping). We measured the patients'
demographics, subjective reports of symptoms, and objective evaluation of the
functional and neurophysiological outcomes of both groups. RESULTS: Group II
patients achieved statistically better results in both neurophysiological scoring
and clinical sensory rating but not in all other parameters. CONCLUSION:
Autogenous vein wrapping for secondary cubital tunnel syndrome after elbow
fracture fixation only provides a better sensory outcome. LEVEL OF EVIDENCE:
Level II, therapeutic prospective comparative study.
PMID- 27616827
TI - Stenosing Tenosynovitis Due to Excessive Texting in an Adolescent Girl: A Case
Report.
AB - We present a case report of stenosing tenosynovitis of the flexor pollicis longus
tendon in an adolescent girl who required surgical release after failing
conservative measures. The patient had no other risk factors, aside from her
excessive texting, which we postulate led to her condition. Although there have
been a few reports of tendinitis and tenosynovitis secondary to texting, we
believe this is the first in the literature to report trigger thumb requiring
surgical release in an adolescent.
PMID- 27616828
TI - A Conservatively Managed Anatomical Variant of the Flexor Digitorum Superficialis
Muscle in the Hand.
AB - Anomalous flexor digitorum superficialis muscles in the hand are an uncommon
phenomenon, and therefore present challenges in diagnosis and management. We
report a case of a 16-year-old girl presenting with a painful, slowly enlarging
palmar swelling. The swelling was investigated with ultrasound and magnetic
resonance imaging, and was found to be an anomalous muscle belly of the flexor
digitorum superficialis muscle. After careful consideration, multidisciplinary
discussion, and thorough imaging, the patient was treated successfully without
surgical exploration or excision, in comparison to previously reported cases. The
patient was pain free and had no concerns at 8-month follow-up, demonstrating the
value of conservative management in these cases.
PMID- 27616830
TI - The Reverse Homodigital Flap Based on the Dorsal Branch of the Digital Artery for
Reconstruction of Acquired Clinodactyly.
PMID- 27616829
TI - Novel Treatment of a Scapholunate Ligament Injury with Proximal Pole Scaphoid
Nonunion.
AB - BACKGROUND: Nonunion of scaphoid proximal pole fractures presents a challenging
management dilemma to hand surgeons. This problem is further complicated in the
uncommon concurrence of scapholunate (SL) ligament disruption. CASE DESCRIPTION:
A 39-year-old male patient presented with new-onset wrist pain following a remote
history of a proximal pole scaphoid fracture sustained as a teenager, which was
treated nonoperatively. Six months before presentation, the patient sustained a
fall while snowboarding. The patient was found to have a chronic nonunion of his
scaphoid proximal pole with an associated SL ligament disruption. As the proximal
fragment was too small to be amenable to fixation, the patient was treated with
an arthroscopic partial scaphoid excision and SL ligament reconstruction using a
scapholunateintercarpal screw placed percutaneously. At 26 months, the patient
exhibited no pain, near-normal strength, and wrist motion, and expressed a high
level of satisfaction from his surgery. LITERATURE REVIEW: Although cases of SL
ligament disruption with concomitant proximal scaphoid fractures have been
reported, to our knowledge, this is the first report of SL ligament rupture
occurring in the setting of a preexisting proximal pole scaphoid nonunion.
CLINICAL RELEVANCE: We report the use of SL ligament reconstruction augmented
with intercarpal screw fixation, and excision of the proximal pole scaphoid
nonunion. This minimallyinvasive approach may be a particularly useful option in
young, active patients such as our own, where a motion-sacrificing salvage
procedure would be less than ideal.
PMID- 27616831
TI - Combined Median and Ulnar Nerve Compression Neuropathy due to Lipoma at the
Wrist.
PMID- 27616832
TI - Symptomatic Rhizarthritis in a Bilateral Scaphotrapezial Synostosis.
PMID- 27616833
TI - Flexor Tendon Laceration Due to Carpal Tunnel Release Surgery: An Impossible
Complication.
PMID- 27616834
TI - 'Use a Thorn to Draw Thorn' Replacement Therapy for Prevention of Dental Caries.
AB - Despite the use of conventional physical and chemotherapeutic agents for caries
management, dental caries still continues to be the most prevalent oral
infectious disease. Thus, there is a need of additional caries prevention
approaches. Strain replacement therapy is one such novel approach. In this,
relatively avirulent strains of Streptococcus mutans produced by recombinant DNA
technology are implanted into the oral cavity. These may either interfere with
the colonization of, or compete with the indigenous cariogenic mutans
streptococci. This technique might provide a cost-effective, long-term means of
achieving tailor made protection for the host against dental caries.
PMID- 27616835
TI - Maxillary Expansion.
AB - Maxillary transverse discrepancy usually requires expansion of the palate by a
combination of orthopedic and orthodontic tooth movements. Three expansion
treatment modalities are used today: rapid maxillary expansion, slow maxillary
expansion and surgically assisted maxillary expansion.This article aims to review
the maxillary expansion by all the three modalities and a brief on commonly used
appliances.
PMID- 27616836
TI - To Evaluate Cytotoxicity of Resin-based Restorative Materials on Human
Lymphocytes by Trypan Blue Exclusion Test: An in vitro Study.
AB - The cytotoxicity of a resin-based material can be evaluated on isolated human
lymphocyte. Since resin-based dental materials have been used with increasing
frequency in anterior and posterior teeth restorations, the uncured resin
monomers are leached out from the restorations and diffuses into the dentine and
ultimately hampers the odontoblastic layers of pulp as well as gingiva. It is
also reaches into the saliva and circulatory blood. The study evaluates and
compares the relative cytotoxicity of resin-based dental materials at different
time interval, i.e. 24, 48, and 72 hours on human lymphocyte by Trypan blue
exclusion method. All resins were found to be cytotoxic to human lymphocyte.
Resin samples cytotoxicity was the highest in first 24 hours followed by 48 and
72 hours.
PMID- 27616837
TI - Evaluation of Microleakage of RMGIC and Flowable Composite Immersed in Soft Drink
and Fresh Fruit Juice: An in vitro Study.
AB - Aim : The objective of the study was to evaluate and compare the effect of a soft
drink and a fresh fruit juice on the microleakage of flowable composite and resin
modified glass lonomer cement (RMGIC). Methods and materials : 70 non-carious
human premolars were collected and stored in saline until further use. Class-V
cavities were prepared and restored with RMGIC on the buccal surface and flowable
composite on the lingual surface for evaluating microleakage. The experimental
groups (Group I and II ) comprised of 60 teeth, while the remaining 10 formed the
control group (Group III-Water). The experimental groups were further divided
into 2 groups (Group I-Cola drink and Group II-Fresh orange fruit juice) of 30
teeth each. Each group was then further divided into 3 subgroups (Short, Medium
and Long-immersion) containing 10 teeth as shown in flow chart. Immersion regime
was followed according to Maupome G et al and microleakage was evaluated by using
Rhodamine B dye and examined under stereomicroscope. Results : Microleakage data
obtained was statistically analyzed by Chi-square test. The teeth showed
statistically significant microleakage as the immersion regime increased.
Interpretation and Conclusion : Low pH soft drink caused highly significant
microleakage at the tooth and restorative material interface in medium and high
immersion regimes signifying that the leakage pattern was directly proportional
to the number of immersions. Thus, the study conclusively proves that the
'sipping habit' associated with commonly available low pH beverages is
detrimental to the longevity of restorations.
PMID- 27616838
TI - Evaluation of Parental Nasomaxillary Asymmetry as a Risk Factor for Development
of Palatal Clefts in their Offsprings.
AB - Background and Objectives : It has been suggested previously that increased width
of midfacial structure is associated with the development of palatal clefting.
One of the most important heritable characteristics predisposing towards the
development of orofacial clefting in an embryo is craniofacial morphology. The
aim of the study was to compare nasomaxillary width of parents of children with
unilateral complete cleft lip alveolus and palate with parents of noncleft
children. Methods : 25 biologic parent sets of children with unilateral complete
cleft lip alveolus and palate and 25 biologic parents of noncleft children were
included in this study for PA cephalometric analysis. Results : There was no
statistically significant difference between study and control groups. An
association was found between the side of the cleft in the affected children and
the parents in the same side with narrower nasomaxillary width. Interpretation
and conclusion : The result of this study was in contrast with other previous
studies. We observed a narrower nasomaxillary width, which suggested that this
feature may be of morphogenetic importance in the etiopathogenesis of orofacial
clefting in this geographic and ethnic group.
PMID- 27616839
TI - Cleanliness in the Root Canal System: An Scanning Electron Microscopic Evaluation
of Manual and Automated Instrumentation using 4% Sodium Hypochlorite and EDTA
(Glyde File Prep)-An in vitro Study.
AB - Aim : To assess the cleaning efficacy of manual and automated instrumentation
using 4% sodium hypochlorite singly and in combination with Glyde file Prep as
root canal irrigant. Methodology : The study utilized 40 extracted human
permanent premolars with single, straight and fully formed root. The teeth were
then divided into four groups of ten each, Group I and II were prepared by manual
instruments with 4% sodium hypochlorite used as irrigant singly [Group I] or in
combination with Glyde file prep. Group III and IV were prepared by automated
instruments at 250 rpm with 4% sodium hypochlorite as irrigant singly [Group III]
and in combination with glyde file prep [Group IV] automated instrumentation.
After completion of the root canal preparation the canal, teeth were prepared for
SEM examination. These photomicrographs were qualitatively evaluated using
criteria. Overall cleanliness, presence or absence of the smear layer, presence
or absence of the debris, patency of the opening of dentinal tubules. Results :
When comparing the cleansing efficacy of manual and automated instrumentation
using 4% sodium hypochlorite better cleansing was there with manual
instrumentation. When comparing the cleansing efficacy of manual and automated
instrumentation using combination regime cleansing is better with automated
instrumentation. When comparing the cleansing efficacy of manual instrumentation
using 4% sodium hypochlorite singly and in combination with EDTA, the combination
regime led to better cleansing. When comparing the cleansing efficacy of
automated instrumentation using 4% sodium hypochlorite singly and in combination
regime lead to better cleansing. Conclusion : Neither of instrumentation
technique, nor irrigating regimes were capable of providing a completely clean
canal. Automated instrumentation with a combination of sodium hypochlorite & EDTA
resulted the best cleansing efficacy.
PMID- 27616840
TI - Staining of a Conventional and a Nanofilled Composite Resin Exposed in vitro to
Liquid Ingested by Children.
AB - Aims and objective : To evaluate and compare the effect of coffee, chocolate
drink and food dye on the color stability of conventional composite resin and
nanocomposite resin. Design : The study sample consists of microhybrid composite
and other nanocomposite of shade B1. 40 disks of each material with a diameter of
18 mm and thickness of 1 mm were prepared before discoloration procedure
specimens were measured for L* a* b* values and then 10 specimens of each
subgroup were immersed in each of three staining solution. The 10 remaining
specimens of each main group were immersed in control solution. Discoloration
values were analyzed at baseline, 1 week and 4 weeks following immersion in
staining solution. The color and color difference of each specimen were measured
by spectrophotometer. L* a * b* values of each specimens were measured 3 times by
placing each specimen on the measuring head. Resistance to staining effect is
expressed in DeltaE unit and was calculated from the mean DeltaL* a* and Deltab*
values for each specimens with the following formula. Equation : DeltaE* =
[(DeltaL*)(2) + (Deltaa*) + (Deltab*)(2)]1/2. Result : Result of study showed
that nanocomposite is more stain resistant and color change DeltaE*. Conventional
composite demonstrates unacceptable color change DeltaE* more especially in
specimens immersed in coffee. Conclusion : The result of this study indicated
tested conventional composite resin was more susceptible to change in color in
various media over an extended period of time as compared to nanocomposite.
PMID- 27616842
TI - Dentigerous Cyst of Inflammatory Origin.
AB - A dentigerous cyst encloses a crown of an unerupted tooth by its follicle and is
attached to the neck of the tooth. They may be of developmental or inflammatory
origin. Dentigerous cyst of inflammatory origin occurs in immature tooth as a
result of inflammation from preceding non-vital deciduous tooth or from other
source spreading to involve the tooth follicle. These are diagnosed in the first
and early part of second decade either on routine radiographic examination or
when patient complains of swelling and pain. They generally involve mandibular
premolars. This article presents a case report of an 11-year-old male patient
with a dentigerous cyst of inflammatory origin in the left mandibular premolar
region with radiographic feature of a large unilocular radiolucency involving
unerupted second premolar. The treatment rendered in this patient comprised of
surgical enucleation of cyst under local anesthesia along with extraction of
mandibular first and second primary molars.
PMID- 27616841
TI - Prevalence of Oral Mucosal and Extraoral Lesions among Cleft Lip and Cleft Palate
Patients Attending to a Private Hospital, India.
AB - Aim of the Study : To assess the prevalence of oral mucosal and extraoral lesions
among the cleft lip and/or palate subjects aged between 3 and 18 years, and to
compare with those of noncleft controls. Methodology : A cross sectional survey
was conducted during the period of March 2004 to September 2004. A select sample
of 150 cases consisted of cleft lip and/or palate subjects aged between 3 and 18
years reporting to Outpatient Department, Plastic and Reconstructive Surgery,
private Hospital and Medical Research Center, Belgaum. A sample of 450 matched
noncleft subjects (Controls) was selected based on convenience from general
population. Oral health assessment form as prescribed in Basic Oral Health
Surveys, WHO, was used to record the data. Results : Approximately 43% of cleft
subjects had abnormalities of upper lip. 7% of clefts and 5% of noncleft controls
presented enlarged lymph nodes on palpation in the head and neck region. Both the
cleft subjects and noncleft controls had ulcerations in the buccal mucosa.
However, there was no significant difference between them. Among few cleft
subjects abscess formation was observed in the sulcus region (1.33%) as well as
gingiva (2.66%) adjacent to cleft. Similarly among controls also few abscess in
sulcus and gingival region were observed. Conclusions : On intra-and extraoral
examination of cleft and noncleft subjects for any lesions revealed that clefts
as well as noncleft subjects exhibited few intraoral lesions, however clinically
or statistically significant differences were not observed.
PMID- 27616843
TI - Systemic Lupus Erythematosus in a 12-Year-Old Boy: A Rare Entity in Childhood.
AB - Childhood onsets of systemic lupus erythematosus (SLE) are quite rare and
comprise less than 20% of all cases of lupus. Prepubertal onset is even rarer, as
most children with SLE belong to the adolescent age group. SLE is an immune
complex mediated disease with multiple organ system involvement, which may lead
to high mortality and morbidity. We report a 12-year-old boy with SLE who
presented clinically with malar rashes, joint pain and oral ulcers.
PMID- 27616844
TI - Multiple Intranasal Foreign Bodies: An Incidental Diagnosis.
AB - Inquisitive children often insert foreign bodies into their nose or other body
orifices while they explore their own bodies in early childhood. Intranasal
foreign bodies are found in children, most commonly in 2-4 years olds. Common
symptoms in such cases include pain or discomfort, nasal discharge, nasal
congestion, nasal odor, including bromhidrosis (foul body odor). Complications,
such as facial cellulitis, epiglottitis, and cephalic tetanus have also been
reported. Mentally challenged children may be at a higher risk for such foreign
body insertion and may need to be examined at regular intervals. Careful
interpretation of dental radiographs can go a long way in diagnosing such cases
especially in the absence of a positive history. Radiolucent objects are more
difficult to identify especially in the absence of a positive history, and hence
their diagnosis and removal is more challenging for the clinician. Dental
practitioners can play a significant role in the diagnosis of intranasal foreign
bodies in children through careful clinical examination and interpretation of
dental radiographs. This case report describes a child referred for dental care
and a diagnosis of intranasal foreign body was made based on routine dental
panoramic radiograph.
PMID- 27616846
TI - Submerged and Impacted Primary Molars.
AB - Submerged tooth is the one that is depressed below the occlusal plane. Dental
ankylosis is thought to be a major cause of submergence. Submerged deciduous
teeth have the potential to cause malocclusion not only by prevention of their
exfoliation and subsequent replacement by permanent teeth but also by causing
tilting of proximal teeth and extrusion of opposing tooth. The purpose of this
report is to present three different cases of submerged deciduous teeth and their
clinical effects.
PMID- 27616845
TI - Prosthetic Rehabilitation in Marble Bone Disease.
AB - Osteopetrosis is a rare metabolic disease.(1) Dental abnormalities may be
attributed to the pathological changes in osteopetrosis. Patients with
osteopetrosis are especially susceptible to osteomyelitis of mandible.(1) A 13
year-old girl presented with complaint of jaw swelling on left side. The
radiograph of left mandible (lateral oblique view) showed small sequestrum with
irregularity and erosions of the man-dibular cortical margins. This case report
aims at diagnosis and treatment of osteopetrosis with superadded mandibular
osteomyelitis-a are entity.
PMID- 27616847
TI - Hyper IgE Disorder Associated with Multiple Fused Primary Teeth: A Rare Clinical
Occurrence.
AB - The hyperimmunoglobulin E syndrome (HIES) is a multisystem disorder that affects
the dentition, skeleton, connective tissues and immune system. Little is known
about oral manifestations of the syndrome. The purpose of this report was to
describe a 6-year-old boy with suspected autosomal recessive HIES syndrome who
had multiple fused primary teeth, which is a rare association with JOB syndrome.
The patient gave a history of pneumonia and skin infections. Recognition of such
case at an early age is necessary to reduce morbidity. As conclusion, treatment
for this condition is life long administration of therapeutic doses of
penicillinase-resistant penicillin, with the addition of other antibiotics or
antifungal agents as required for specific infections.
PMID- 27616848
TI - Nonsyndromic Bilateral Maxillary and Unilateral Mandibular Multiple Dentigerous
Cysts in a Young Girl: Report of a Rare Case.
AB - Dentigerous cyst is a benign odontogenic cyst associated with the crowns of
permanent teeth. It is usually single in occurrence and located in the mandible
of middle-aged persons. The teeth commonly affected are in order of frequency,
the mandibular third molars, maxillary canines, maxillary third molars and,
rarely central incisors. The present case report describes the surgical
enucleation of the huge bilateral maxillary dentigerous cysts involving permanent
maxillary canines associated with unilateral mandibular lateral incisor, cuspid
and bicuspids in a young girl. To our knowledge, bilateral maxillary and
unilateral mandibular multiple dentigerous cysts in a nonsyndromic patient have
not been reported previously in the literature.
PMID- 27616849
TI - Occult Caries: The Hidden Truth.
AB - The term "occult caries" and "hidden caries" are used to describe such lesions,
which are not clinically diagnosed but detected only on radiographs. A female
patient aged 14 years reported for routine dental check-up. On Intraoral
examination, sinus was seen in the buccal mucosa of maxillary left second
premolar 25. On clinical examination the occlusal surface remained ostensibly
intact; tooth was asymptomatic with no past history of pain. On radiographic
examination, there was radiolucency in distobuccal aspect of 25 involving enamel,
dentin and nearing pulp with presence of open apex and periapical radiolucency
irt 25. With clinical and radiographic evaluation, the case was diagnosed as
occult caries in relation to 25. Apexification was done with calcium hydroxide.
The tooth is under observation; once radiographic barrier is formed conventional
root canal treatment will be performed. Conclusion : Early diagnosis of occult
lesions is the best management. As radiographs are probably the most effective
method of diagnosing all occult lesions, they should be recommended at
appropriate ages to aid early detection of these lesions.
PMID- 27616850
TI - Guest Editorial.
PMID- 27616851
TI - Diagnostic Aids in Pediatric Dentistry.
AB - Diagnosis involves development of a comprehensive and concise database of
pertinent information, sufficient to understand the patient's problem as well as
answer questions arising in the treating clinicians' mind. It is an accomplished
art to develop a communication with the child and elicit relevant information
from him. Thus, the signs and symptoms elicited on the basis of patient's
experiences and clinician's knowledge forms the elementary framework of a good
prognosis. This article aims to unveil the "must know" fundamentals of a sound
diagnosis for a sound treatment plan.
PMID- 27616852
TI - Effect of Coconut Water Concentration on Survival of Bench-Dried Periodontal
Ligament Cells.
AB - Background : Coconut water is a biological and sterile liquid. It contains a
variety of electrolytes, sugars and amino acids. The purpose of this study is to
evaluate the effect of concentration and maturity of coconut water on its ability
to preserve human PDL cell viability after exposure to dry time of up to 120
minutes using an in vitro cell culture model. Methods : PDL cells were obtained
from sound permanent first molars which were cultured in Dulbecco's Modified
Eagle's Medium (DMEM). Cultures were subjected to 0, 30, 60, 90 and 120 minutes
dry periods then incubated with 100 and 50% young and mature coconut water for 45
minutes at room temperature (18-26 degrees C). Untreated cells at 0 and 120
minutes, and cells incubated in DMEM served as controls. PDL cell viability was
assessed by MTT assay. Statistical analysis of data was accomplished by using one
way analysis of variance complemented by Tukey test, and the level of
significance was 5% (p < 0.05). Results : 100% mature coconut water (MCW) was
better than 50% dilutions obtained from mature or young coconuts. However, no
significant benefit to the cells was noticed from the addition of the soaking
step prior to 30 minutes dry time. Conclusion : Avulsed teeth which are left dry
for > 30 minutes may be benefited from soaking in 100% mature coconut water;
further studies on simulated avulsion in animal models are needed to verify the
above results.
PMID- 27616853
TI - An in vitro Study of Diffusibility and Degradation of Three Calcium Hydroxide
Pastes.
AB - Aims and objectives : The aim of this in vitro study is to assess the
diffusibility and degradation of three calcium hydroxide pastes. Materials and
methods : Three pastes were prepared by mixing calcium hydroxide powder with
three different vehicles namely water, propylene glycol and CMCP for the
investigation. The three pastes were sealed in porcelain caps and immersed in
distilled water for the diffusion study. The change in the pH of the surrounding
water indicated the rate and degree of diffusion in the degradation study (1 to 7
days, 14th day, 21st day and 30th day). The pastes were exposed to an atmosphere
of carbon dioxide in the degradation study to assess the degree to which they can
undergo degradation by carbonation. Mordant Black or Solochrome Black indicator
was used for the estimation. Results and conclusion : Calcium hydroxide readily
diffuses from all the three pastes. Calcium hydroxide diffuses marginally less
from a paste made with propylene glycol as compared to CMCP paste. The
comparative stability of Ca(OH)2 was studied and the results showed that
consistently significant protection is imparted to Ca(OH)2 by CMCP over widely
ranging periods.
PMID- 27616854
TI - Knowledge and Oral Health Attitudes among Parents of Children with Congenital
Heart Disease.
AB - Congenital heart disease (CHD) is a devastating complex of diseases resulting
from defects of development. It affects more than 1 of every 100 live births.
Early preventive dental care should be adjusted to the special needs of these
children in their first years of life. Knowledge of parental attitudes and
experiences of dental care are therefore important. Aim : This study was done to
assess the knowledge and attitudes among parents of children with congenital
heart disease towards oral health and dental care. Materials and methods :
Parents (n = 105) of children with congenital heart disease of an age ranging
from 0 to 16 years were included in the study. A questionnaire was used to assess
the knowledge and oral health attitudes. Results : The parents' knowledge was
fair but the oral health attitudes were not very satisfactory. The parents in
this study also recognized the importance of oral health for the well-being of
rest of the body. Conclusion : The results of this study indicate that parents'
and children's attitudes toward oral health and dental care need to be improved.
PMID- 27616855
TI - Evaluation of the Antimicrobial Effectiveness and the Effect of Dosage and
Frequency of Sugar-free Chewing Gums on Streptococcus mutans Count: An in vivo
Microbiological Study.
AB - The aim of the present study was to evaluate the antimicrobial efficacy of sugar
free chewing gums and also to assess the effect of dosage and frequency of intake
of sugar-free gums on Streptococcus mutans count. Method : The sample consisted
of 30 subjects, divided into two groups AI and AII. Each group consisted of 15
subjects. Group AI chewed two sugar-free chewing gum, twice daily for 20 minutes
(Total four gums daily) and group AII chewed two sugar-free chewing gum, four
times daily for 20 minutes (Total eight gums daily) and saliva sample was
collected and agar plates were inoculated for Streptococcus mutans colony count.
The study was carried for a week's time and saliva samples collected were
baseline, day 1 morning and evening, day 4 evening, day 7 morning and evening.
Results : After the gum was chewed, it was observed that the colony count started
to reduce when compared with baseline in both the groups. The fall in
Streptococcus mutans count was statistically highly significant with p < 0.001 in
both the groups. When comparing between group AI (dosage 4 gums daily) and group
AII (dosage 8 gums daily), the fall in Streptococcus mutans count for both the
groups was not statistically significant with p > 0.05. It was concluded that
there was reduction in the level of salivary Streptococcus mutans, but was not
statistically significant by increasing the dosage and frequency of intake of
sugar-free chewing gums. Therefore, we recommend that dosage of sugar-free
chewing gums can be restricted to four gums instead of eight gums per day.
PMID- 27616856
TI - Behavior Assessment of Children in Dental Settings: A Retrospective Study.
AB - In children, dental anxiety and fear of dental treatment have been recognized as
a source of problems in patient management for many years, which can affect the
quality of care. Aims : The aim of the study was to assess the behavior of
children during their dental visit and to determine the effect of behavior
management techniques on children. Materials and Methods : A retrospective study
was done by analyzing the records of 328 children to assess their behavior during
dental visits. Behavior assessment was done using Frankl's behavior rating scale.
All children were exposed to live modeling and tell-show-do behavior management
technique. Statistical analysis : The analysis was carried out using SPSS version
10. The comparison between visits was carried out by applying Friedman test.
Results and conclusion : Children showed improvement in their behavior with every
subsequent visits. Proper assessment of children's behavior helps the dentist to
execute a required treatment plan in the most appropriate manner. Techniques like
live modeling and tell-show-do are very effective in modifying a child's
behavior.
PMID- 27616857
TI - ABCD of Safe Dental Practice.
AB - Dental practice is the integral component of the oral health. Though the dental
practice is in close relation with that of the medical practice, it has its own
distinctiveness in relation to safe practice. The safe dental practice should not
only assure good oral and general health but also improve social interaction by
enhancing physical appearance, esthetics, etc. For the safe dental practice,
dentists must excel in patient care and standard of treatment. The interlocking
missions of education, research, and patient care are the cornerstones for the
safe and healthy dental practice. This paper is designed to bridge the gap
between the educational preparation of the dentist and the reality of the working
world in a simple way.
PMID- 27616858
TI - Segmental Orthodontics for the Correction of Cross Bites.
AB - Cross bite is a condition where one or more teeth may be abnormally malposed
buccally or lingually or labially with reference to the opposing tooth or teeth.
Cross bite correction is highly recommended as this kind of malocclusion do not
diminish with age. Uncorrected cross bite may lead to abnormal wear of lower
anteriors and cuspal interference, mandibular shift resulting in mandibular
asymmetry and temporomandibular joint dysfunction syndrome. There are several
methods for treating this type of malocclusion. In this article, segmental
orthodontics has been highlighted by using 2 * 4 appliance therapy and lingual
button with cross elastics. This appliance offers many advantages as it provides
complete control of anterior tooth position, is extremely well tolerated,
requires no adjustment by the patient and allows accurate and rapid positioning
of teeth.
PMID- 27616859
TI - Complete Management of a Mutilated Young Permanent Central Incisor.
AB - This case report throws light on treatment of immature apices through
apexogenesis and an esthetic postobturation restoration of traumatized young
permanent central incisor using a relatively newer methodology of anatomic posts,
i.e. shaping the post to the root anatomy. The authors would also like to
underline the significance of rubber dam isolation for more predictable outcomes.
The new method of anatomic post is simple, viable, practical, and less time
consuming than thought.
PMID- 27616860
TI - Surgical Repositioning of a Dilacerated Impacted Incisor.
AB - Dilaceration is one of the most common complications of trauma to deciduous
dentition. The possible causes of dilaceration are trauma and developmental
disturbances, while some authors suggest an association with some developmental
syndromes. Dilaceration can be seen in both the permanent and deciduous
dentition. The present case report describes surgical repositioning of a
dilacerated impacted maxillary central incisor in a 9-year-old boy.
PMID- 27616861
TI - Orthodontic Management of Midline Diastema in Mixed Dentition.
AB - Midline diastema is a space between the central incisors. Although physiologic
transitory maxillary midline diastema is observed in children during eruption of
maxillary anterior teeth in most cases, it is self-corrected after eruption of
maxillary canines. However, midline diastema unrelated to the eruption of teeth
has been observed owing to various etiologic factors. Treatment to align the
central incisors depends on the predisposing factors.
PMID- 27616862
TI - Extensive Mucocutaneous Verruca Vulgaris in a Nonimmunocompromised Patient.
AB - Papilloma virus infections of the oral cavity have been long recognized with
various clinical expressions characterized as verruca vulgaris, Heck's disease,
multiple papilloma and condyloma acuminata. In this paper, we are highlighting a
case of verruca vulgaris involving the oral cavity with extensive skin lesions in
a nonimmunocompromised 9-year-old boy. Different treatment modalities are
discussed in this article.
PMID- 27616863
TI - Platelet Rich Plasma-A Healing Aid and Perfect Enhancement Factor: Review and
Case Report.
AB - Platelet rich plasma (PRP) has been a breakthrough in the stimulation and
acceleration of tissue healing. It represents a relatively new approach in
regenerative procedures and is a developing area in pediatric dentistry. It is an
autologous source of growth factors obtained by sequestrating and concentrating
platelets by gradient density centrifugation. This novel and potentially
promising technique enhances body's natural wound healing mechanism. This article
goes on to describe preparation and clinical benefits of PRP in pediatric
dentistry.
PMID- 27616864
TI - Idiopathic Gingival Fibromatosis.
AB - Idiopathic gingival fibromatosis is a rare heriditary condition characterized by
slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and
mandibular keratinized gingiva caused by increase in submucosal connective tissue
elements. This case report gives an overview of gingival fibromatosis in a 11
year-old female patient who presented with generalized gingival enlargement.
Based on the history and clinical examination, the diagnosis was made and the
enlarged tissue was surgically removed. The patient was being regularly monitored
clinically for improvement in her periodontal condition as well as for any
recurrence of gingival overgrowth.
PMID- 27616865
TI - Gingival Cyst of Newborn.
AB - Gingival cyst of newborn is an oral mucosal lesion of transient nature. Although
it is very common lesion within 3 to 6 weeks of birth, it is very rare to
visualize the lesion thereafter. Presented here is a case report of gingival
cyst, which was visible just after 15 days of birth. Clinical diagnoses of these
conditions are important in order to avoid unnecessary therapeutic procedure and
provide suitable information to parents about the nature of the lesion.
PMID- 27616866
TI - Editorial.
PMID- 27616867
TI - Thermodynamic free energy methods to investigate shape transitions in bilayer
membranes.
AB - The conformational free energy landscape of a system is a fundamental
thermodynamic quantity of importance particularly in the study of soft matter and
biological systems, in which the entropic contributions play a dominant role.
While computational methods to delineate the free energy landscape are routinely
used to analyze the relative stability of conformational states, to determine
phase boundaries, and to compute ligand-receptor binding energies its use in
problems involving the cell membrane is limited. Here, we present an overview of
four different free energy methods to study morphological transitions in bilayer
membranes, induced either by the action of curvature remodeling proteins or due
to the application of external forces. Using a triangulated surface as a model
for the cell membrane and using the framework of dynamical triangulation Monte
Carlo, we have focused on the methods of Widom insertion, thermodynamic
integration, Bennett acceptance scheme, and umbrella sampling and weighted
histogram analysis. We have demonstrated how these methods can be employed in a
variety of problems involving the cell membrane. Specifically, we have shown that
the chemical potential, computed using Widom insertion, and the relative free
energies, computed using thermodynamic integration and Bennett acceptance method,
are excellent measures to study the transition from curvature sensing to
curvature inducing behavior of membrane associated proteins. The umbrella
sampling and WHAM analysis has been used to study the thermodynamics of tether
formation in cell membranes and the quantitative predictions of the computational
model are in excellent agreement with experimental measurements. Furthermore, we
also present a method based on WHAM and thermodynamic integration to handle
problems related to end-point-catastrophe that are common in most free energy
methods.
PMID- 27616868
TI - Validation of the Parenting Stress Index-Short Form With Minority Caregivers.
AB - OBJECTIVES: There has been little examination of the structural validity of the
Parenting Stress Index-Short Form (PSI-SF) for minority populations in clinical
contexts in the Unites States. This study aimed to test prespecified factor
structures (one-factor, two-factor, and three-factor models) of the PSI-SF.
METHODS: This study used confirmatory factor analysis in a sample of 240
predominantly Black and Latino caregivers of children with behavioral
difficulties. RESULTS: The three-factor model fit was reasonable, and the
criterion validity for the subscale and total scores was good supporting
continued cautious use of the PSI-SF for clinical minority populations.
CONCLUSIONS: The PSI-SF could be integrated as part of screening and intake
assessment procedures, which could allow social work practitioners to make more
informed decisions about treatment planning, as well as facilitate conversations
with caregivers around identifying sources of stress and developing healthy
coping strategies.
PMID- 27616870
TI - Depressive Symptoms and their Association With Adverse Environmental Factors and
Substance Use in Runaway and Homeless Youths.
AB - We used diathesis-stress and stress-sensitization models to determine whether
family maltreatment, street-related traumatic events, stressful life events, and
substance use were associated with depressive symptoms in runaway and homeless
youths (RHY) in Los Angeles. Greater severity of depressive symptoms was
significantly related to family maltreatment, being exposed to more traumatic
stressors during homelessness, and current substance use compared to no substance
use. Family maltreatment was also found to moderate the relationship between
traumatic stressors and depressive symptoms. Importantly, cumulative exposure to
the investigated risk factors at varying levels was associated with more severe
depressive symptoms. Using a trauma-informed approach to screen for RHY at risk
of depression may pave the way for secondary prevention of major depression in
RHY.
PMID- 27616869
TI - Measuring Use of Research Evidence: The Structured Interview for Evidence Use.
AB - OBJECTIVES: This article describes the Standard Interview for Evidence Use
(SIEU), a measure to assess the level of engagement in acquiring, evaluating, and
applying research evidence in health and social service settings. METHOD: Three
scales measuring input, process, and output of research evidence and eight
subscales were identified using principal axis factor analysis and parallel
analysis of data collected from 202 state and county child welfare, mental
health, and juvenile justice systems leaders. RESULTS: The SIEU scales and
subscales demonstrate strong internal consistency as well as convergent and
discriminant validity. CONCLUSIONS: The SIEU is easy to use and can be
administered as a complete scale or as three smaller scales to separately examine
evidence in acquisition, evaluation, or application. The measure demonstrates
potential in understanding the role of research evidence in service settings and
in monitoring the process of evidence-based practice and application of
scientific principles in social work practice.
PMID- 27616871
TI - Testing the Parent-Adolescent Acculturation Discrepancy Hypothesis: A Five-Wave
Longitudinal Study.
AB - This 21/2-year, 5-wave longitudinal study tests the hypothesis that acculturation
discrepancies between Hispanic immigrant parents and adolescents would lead to
compromised family functioning, which would then lead to problematic adolescent
outcomes. Recent-immigrant Hispanic parent-adolescent dyads (N = 302) completed
measures of acculturation and family functioning. Adolescents completed measures
of positive youth development, depressive symptoms, problem behavior, and
substance use. Results indicated that Time 1 discrepancies in Hispanic-culture
retention, and linear trajectories in some of these discrepancies, negatively
predicted adolescent positive youth development, and positively predicted
adolescent depressive symptoms and binge drinking, indirectly through adolescent
reported family functioning. The vast majority of effects were mediated rather
than direct, supporting the acculturation discrepancy hypothesis. Implications
for further research and intervention are discussed.
PMID- 27616872
TI - Determination of Total Chondroitin Sulfate in Dietary Ingredients and
Supplements.
PMID- 27616873
TI - Impact of Brief Intervention Services on Drug-Using Truant Youths' Self-Reported
Delinquency and Arrest Charges: A Longitudinal Study.
AB - The issue of delinquency among truant youth is insufficiently documented in the
literature. There is a need to elucidate this issue, and assess the efficacy of
interventions to reduce this problem behavior. The present, NIDA-funded study
addressed this gap by examining the impact of a Brief Intervention (BI),
originally designed to address youth substance use, on their delinquent behavior
over an 18-month follow-up period (for self-reported delinquency) and a 24-month
follow-up period (for official record delinquency). A number of significant BI
intervention effects with sizable effect sizes were found, as well as a number of
marginally significant BI effects. In particular, significant reductions in
arrest charges at 24-month follow-up for youth receiving BI services compared to
controls were among the key findings of this study. Service delivery implications
and directions for future analyses are discussed.
PMID- 27616874
TI - Cognitive-Behavioral Therapy for ADHD in Adolescents: Clinical Considerations and
a Case Series.
AB - Although ADHD in adolescents is an impairing and prevalent condition, with
community prevalence estimates between 2% and 6%, psychosocial treatments for
adolescents compared to younger children are relatively understudied. Our group
has successfully developed an evidence base for cognitive-behavioral therapy
(CBT) for ADHD in medication-treated adults with ADHD with clinically significant
symptoms. In the current paper, we describe an adaptation of this treatment to
adolescents, and provide case reports on 3 adolescents who participated in an
open pilot trial. The results suggest that the treatment approach was well
tolerated by the adolescents and that they experienced clinical benefit. This
early report of the approach in adolescents is promising and requires further
efficacy testing.
PMID- 27616875
TI - Housing hardship and energy insecurity among native-born and immigrant low-income
families with children in the United States.
AB - The costs for rent and utilities account for the largest share of living
expenses, yet these two critical dimensions of material hardship have seldom been
examined concurrently in population-based studies. This paper employs
multivariate statistical analysis using American Community Survey data to
demonstrate the relative risk ratio of low-income renter-occupied households with
children experiencing "rent burden," "energy insecurity," or a "double burden" as
opposed to no burden. Findings suggest that low-income households are more likely
to experience these economic hardships in general but that specific groups are
disproportionately burdened in different ways. For instance, whereas immigrants
are more likely to experience rental burden, they are less likely to experience
energy insecurity and are also spared from the double burden. In contrast, native
born African Americans are more likely than all other groups to experience the
double burden. These results may be driven by the housing stock available to
certain groups due to racial residential segregation, decisions regarding the
quality of housing low-income householders are able to afford, as well as home
country values, such as modest living and energy conservation practices, among
immigrant families. This paper also points to important policy gaps in safety net
benefits related to housing and energy targeting low-income households.
PMID- 27616876
TI - Differentially Private Frequent Subgraph Mining.
AB - Mining frequent subgraphs from a collection of input graphs is an important topic
in data mining research. However, if the input graphs contain sensitive
information, releasing frequent subgraphs may pose considerable threats to
individual's privacy. In this paper, we study the problem of frequent subgraph
mining (FGM) under the rigorous differential privacy model. We introduce a novel
differentially private FGM algorithm, which is referred to as DFG. In this
algorithm, we first privately identify frequent subgraphs from input graphs, and
then compute the noisy support of each identified frequent subgraph. In
particular, to privately identify frequent subgraphs, we present a frequent
subgraph identification approach which can improve the utility of frequent
subgraph identifications through candidates pruning. Moreover, to compute the
noisy support of each identified frequent subgraph, we devise a lattice-based
noisy support derivation approach, where a series of methods has been proposed to
improve the accuracy of the noisy supports. Through formal privacy analysis, we
prove that our DFG algorithm satisfies epsilon-differential privacy. Extensive
experimental results on real datasets show that the DFG algorithm can privately
find frequent subgraphs with high data utility.
PMID- 27616877
TI - The politics of environmental concern: A cross-national analysis.
AB - Prior research in the U.S. has found that liberals are generally more
environmentally concerned than conservatives. The present study explores whether
conservatives' opposition to environmental protection is solely a U.S. or a
universal phenomenon and whether this association is contingent on country-level
characteristics such as development, environmental conditions, and communist
history. Employing data for 19 countries from the ISSP module "Environment II,"
this paper explores inter-country variations in the relationship between
individual conservatism and environmental concern using multilevel modeling with
cross-level interactions. The models reveal a number of intriguing associations.
Most important, conservatives' support for environmental protection varies by
country. This variation is a function of country-level characteristics. The
strongest opposition of conservatives' toward environmental protection was
observed in developed, capitalist nations, with superior environmental
conditions. On the other hand, in less developed countries, and countries
characterized by poor environmental quality, conservatives are more
environmentally concerned than liberals.
PMID- 27616878
TI - Optimal Drug Policy in Low-Income Neighborhoods.
AB - The control of drug activity currently favors supply-side policies: drug
suppliers in the U.S. face a higher arrest rate and longer sentences than
demanders. We construct a simple model of drug activity with search and entry
frictions in labor and drug markets. Our calibration analysis suggests a strong
"dealer replacement effect." As a result, given a variety of community
objectives, it is beneficial to lower supplier arrests and raise the demand
arrest rate from current values. A 10% shift from supply-side to demand-side
arrests can reduce the population of potential drug dealers by 22-25,000 and
raise aggregate local income by $380-400 million, at 2002 prices. (JEL
Classification: D60, J60, K42, H70).
PMID- 27616879
TI - The outcomes and prognostic factors of vitrectomy in chronic diabetic traction
macular detachment.
AB - PURPOSE: To investigate the outcomes of pars plana vitrectomy (PPV) for chronic
diabetic traction macular detachment (CTMD). METHODS: Ninety-six eyes that
underwent PPV for CTMD of at least 6 months duration were retrospectively
analyzed. Retinal reattachment rate, final vision, and prognostic factors for
poor visual outcome were the main outcome measures. RESULTS: All eyes had long
standing TMD (median 12, range: 6-70 months). The median postoperative follow-up
was 15 (range: 3-65) months. Eighty-seven eyes (90.6%) had their retina and
macula reattached after one PPV. At final examination, 84 eyes (87.5%) had stable
vision or at least one line improvement, and three had no light perception.
Seventeen (17.7%) and 41 (43%) eyes had preoperative visual acuity of >=20/200
and >=5/200 as compared to 40 (41.6%; P=0.0005) and 64 (66.7%; P=0.0014) eyes at
final follow-up, respectively. Age >50 years (Odds ratio [OR] =5.84, 95%
confidence interval [CI] =1.53-22.19, P=0.01), preoperative vision <20/400 (OR
=7.012, 95% CI =1.82-26.93, P=0.005), and ischemic macula (OR =14.13, 95% CI
=3.61-55.33, P<0.001) were significantly associated with final vision <20/400.
CONCLUSION: PPV for CTMD may be beneficial particularly in patients who are
relatively younger and have good baseline vision and no macular ischemia.
PMID- 27616880
TI - Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced
atherosclerosis.
AB - OBJECTIVE: There is increasing evidence supporting the role of platelets in
atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a
central mediator of platelet activation and aggregation but has also been linked
to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist
that is used as a standard treatment in patients after acute myocardial
infarction. However, the effects of ticagrelor on advanced atherosclerosis have
not been investigated. MATERIALS AND METHODS: Twenty-week-old apolipoprotein-E
deficient mice received standard chow or standard chow supplemented with 0.15%
ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was
evaluated in the aortic sinus by Movat's pentachrome staining and lesion
composition, thickness of the fibrous cap, and size of the necrotic core
evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated
with ticagrelor in vitro for the detection and quantification of apoptosis. In
addition, oxLDL uptake in RAW 264.7 macrophages was evaluated. RESULTS: A trend
toward the reduction of total lesion size was detected. However, data did not
reach the levels of significance (control, n=11, 565,881 MUm(2) [interquartile
range {IQR} 454,778-603,925 MUm(2)] versus ticagrelor, n=13, 462,595 MUm(2) [IQR
379,740-546,037 MUm(2)]; P=0.1). A significant reduction in the relative area of
the necrotic core (control, n=11, 0.46 [IQR 0.4-0.51] versus ticagrelor, n=13,
0.34 [IQR 0.31-0.39]; P=0.008), and a significant increase in fibrous caps
thickness (control, n=11, 3.7 MUm [IQR 3.4-4.2 MUm] versus ticagrelor, n=13, 4.7
[IQR 4.3-5.5 MUm], P=0.04) were seen in ticagrelor-treated mice. In vitro studies
demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07+/-0.03
versus ticagrelor 0.03+/-0.03; P=0.0002) when incubated with ticagrelor. Uptake
of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor
(control 9.2 [IQR 5.3-12.9] versus ticagrelor 6.4 [IQR 2.5-9.5], P=0.02).
CONCLUSION: The present study demonstrates for the first time a plaque
stabilizing effect of ticagrelor in a model of advanced vascular disease,
potentially induced by a reduction of oxLDL uptake or an inhibition of apoptosis
as seen in vitro.
PMID- 27616881
TI - Impact of fixed orthodontic appliance or clear-aligner on daily performance, in
adult patients with moderate need for treatment.
AB - OBJECTIVE: To assess the impact of wearing fixed orthodontic appliance (FOA) or
clear-aligner, on daily performance in adult patients. METHODS: The Oral Impacts
on Daily Performance (OIDP) index was assessed in 152 adults aged 25-35 years at
baseline (T0), 6 months after bonding (T1), and 12 months after bonding (T2).
Participants were randomly divided into two groups: CA group (participants
treated with clear-aligner) and a control group (FOA group; participants treated
with FOA). Baseline malocclusion severity was assessed using the Index of
Orthodontic Treatment Need. RESULTS: There were no significant differences in
sociodemographic variables and OIDP scores at baseline between the two groups.
Significant changes in OIDP total and subscale scores were observed while wearing
FOA: OIDP total score and subscale scores of eating, cleaning teeth, smiling, and
social relation at T1 and T2 were significantly higher than at baseline (P<0.05
or P<0.01). However, only OIDP total score was significantly increased at T1
compared to the baseline in the CA group. OIDP total score and subscale scores of
eating, cleaning teeth, smiling, and social relation were significantly higher in
patients wearing FOA than in patients wearing clear-aligner at T1 and T2 (P<0.05
or P<0.01). CONCLUSION: Patients wearing clear-aligner have fewer impacts on
daily life than those wearing FOA during treatment, and have no significant
changes in OIPD subscale scores at 12 months. FOA therapy significantly impacts
daily performance in adult patients during treatment.
PMID- 27616882
TI - Self-reported quality of life in multiple sclerosis patients: preliminary results
based on the Polish MS Registry.
AB - BACKGROUND: The aim of the study was to analyze selected clinical and
sociodemographic factors and their effects on the quality of life (QoL) of
multiple sclerosis (MS) patients registered in the Polish MS Registry. METHODS:
This was a cross-sectional observational study performed in Poland. Data on
personal and disease-specific factors were collected between January 1, 2011, and
December 31, 2015, via the web portal of the Polish MS Registry. All patients
were assessed by a physician and asked to complete the Polish language versions
of the following self-evaluation questionnaires: EuroQol 5-Dimensions, EuroQoL
Visual Analog Scale, and Multiple Sclerosis Impact Scale. Univariate analysis and
logistic regression were performed to determine the factors associated with QoL.
RESULTS: The study included 2,385 patients (female/male ratio 2.3:1) with
clinically confirmed MS (mean age 37.8+/-9.2 years). Average EuroQol 5-Dimensions
index was 0.72+/-0.24, and the mean EuroQoL Visual Analog Scale score was 64.2+/
22.8. The average Multiple Sclerosis Impact Scale score was 84.6+/-11.2 (62.2+/
18.4 for physical condition and 23.8+/-7.2 for mental condition). Lower QoL
scores were significantly associated with higher level of disability (odds ratio
[OR], 0.932; 95% confidence interval [CI], 0.876-0.984; P=0.001), age >40 years
(OR, 1.042; 95% CI, 0.924-1.158; P=0.012), longer disease duration (OR, 0.482;
95% CI, 0.224-0.998; P=0.042), and lack of disease modifying therapies (OR,
0.024; 95% CI, 0.160-0.835; P=0.024). No significant associations were found
between QoL, sex, type of MS course, patient's education, and marital status.
CONCLUSION: The Polish MS Registry is the first national registry for long-term
observation that allows for self-evaluation of the QoL. QoL of Polish patients
with MS is significantly lower compared with the rest of the population. The
parameter is mainly affected by the level of disability, duration of the disease,
and limited access to immunomodulatory therapy.
PMID- 27616883
TI - Polypharmacy in older adults with human immunodeficiency virus infection compared
with the general population.
AB - BACKGROUND: The percentage of older HIV-positive patients is growing, with an
increase in age-related comorbidities and concomitant medication. OBJECTIVES: To
quantify polypharmacy and profile types of non-antiretroviral drugs collected at
community pharmacies in 2014 by HIV-positive individuals on antiretroviral
therapy and to compare these findings with those of the general population.
METHODS: HIV-positive patients (n=199) were compared with a group of patients
from the general population (n=8,172), aged between 50 and 64 years. The factors
compared were prevalence of polypharmacy (>=5 comedications with cumulative
defined daily dose [DDD] per drug over 180), percentage of patients who collected
each therapeutic class of drug, and median duration for each drug class (based on
DDD). Results were stratified by sex. RESULTS: Polypharmacy was more common in
HIV-positive males than in the male general population (8.9% vs 4.4%, P=0.010).
Polypharmacy was also higher in HIV-positive females than in the female general
population (11.3% vs 3.4%, P=0.002). Percentage of HIV-positive patients
receiving analgesics, anti-infectives, gastrointestinal drugs, central nervous
system (CNS) agents, and respiratory drugs was higher than in the general
population, with significant differences between male populations. No differences
were observed in proportion of patients receiving cardiovascular drugs. The
estimated number of treatment days (median DDDs) were higher in HIV-positive
males than in males from the general population for anti-infectives (32.2 vs
20.0, P<0.001) and CNS agents (238.7 vs 120.0, P=0.002). A higher percentage of
HIV-positive males than males from the general population received sulfonamides
(17.1% vs 1.5%, P<0.001), macrolides (37.1% vs 24.9%, P=0.020), and quinolones
(34.3% vs 21.2%, P=0.009). CONCLUSION: Polypharmacy is more common in HIV
positive older males and females than in similarly aged members of the general
population. HIV-positive patients received more CNS drugs and anti-infectives,
specifically sulfonamides, macrolides, and quinolones, but there were no
differences in the percentage of patients receiving cardiovascular drugs. It is
essential to investigate nonantiretroviral therapy medication use in the HIV
positive population to ensure these patients receive appropriate management.
PMID- 27616884
TI - The objective evaluation of obstructive pulmonary diseases with spirometry.
AB - Airway obstruction is variable in asthma, while it is progressive and persistent
in chronic bronchitis and emphysema. However, some of the patients presenting
with symptoms of chronic airway diseases have clinical features of both asthma
and COPD. The group with "Asthma-COPD Overlap Syndrome" (ACOS) phenotype was
characterized by definitely irreversible airway obstruction accompanied by
symptoms and signs of reversibility. In this study, we aimed to classify
obstructive airway diseases by clinical, radiological, and pulmonary function
tests. Patients at Samsun Medical Park Hospital Chest Diseases outpatient clinic
were evaluated between January 2013 and April 2016, and a total of 235 patients
were included in this study. Mean age of the patients was 55.3+/-14.5 (15-88)
years, and the male/female ratio was 45/190. The baseline pulmonary function test
results of the patients were as follows: mean forced vital capacity (FVC) values
2,825+/-1,108 (710-6,870) mL and 74.3+/-22.4 (24-155)%, forced expiratory volume
in 1 second (FEV1) values 1,789+/-774 (480-4,810) mL and 58.1+/-20.0 (20-130)%,
FEV1/FVC values 62.5+/-6.8 (39-70)%. Reversibility criteria following
bronchodilator treatment were present in 107 (45.5%) patients. We specified five
subgroups for patients according to their clinical, radiological, and pulmonary
test findings, namely Group 1 (asthma), Group 2 (ACOS), Group 3 (chronic
bronchitis), and Group 4 (emphysema). Additionally, a group of patients who had
clinical and spirometric features of both asthma and chronic bronchitis in
association with underlying emphysema (emphysema with chronic bronchitis and
emphysema with asthma) was defined as the undifferentiated obstruction (UNDO)
group. Number and percentage distribution of patients by groups were 58 (24.7%)
in the asthma group, 70 (29.8%) in the ACOS group, 61 (26%) in the chronic
bronchitis group, 32 (13.6%) in the emphysema group, and 14 (6%) in the UNDO
group. In conclusion, in our study, the types of obstructive airway diseases
could be classified based on clinical, radiological, and pulmonary function test
findings into five groups, including asthma, ACOS, chronic bronchitis, emphysema,
and both asthma and chronic bronchitis in association with underlying emphysema
(emphysema with chronic bronchitis and emphysema with asthma) or the so-called
undifferentiated obstruction. We suggest that these patient groups can be
determined more accurately by studies that evaluate the association between
spirometric FEV1, FEV1/FVC values, and reversibility ratios.
PMID- 27616885
TI - Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein
levels in patients with mild COPD.
AB - PURPOSE: COPD is mainly caused by tobacco smoking and is associated with a high
frequency of coronary artery disease. There is growing recognition that the
inflammation in COPD is not only confined to the lungs but also involves the
systemic circulation and can impact nonpulmonary organs, including blood vessels.
alpha1-antitrypsin-low-density lipoprotein (AT-LDL) complex is an oxidatively
modified LDL that accelerates atherosclerosis. Curcumin, one of the best
investigated natural products, is a powerful antioxidant. However, the effects of
curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin((r)), a
highly absorptive curcumin with improved bioavailability using a drug delivery
system, ameliorates the inflammatory status in subjects with mild COPD. PATIENTS
AND METHODS: This is a randomized, double-blind, parallel-group study. Subjects
with stages I-II COPD according to the Japanese Respiratory Society criteria were
randomly assigned to receive 90 mg Theracurmin((r)) or placebo twice a day for 24
weeks, and changes in inflammatory parameters were evaluated. RESULTS: There were
no differences between the Theracurmin((r)) and placebo groups in terms of age,
male/female ratio, or body mass index in 39 evaluable subjects. The percent
changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride,
or high-density lipoprotein-cholesterol levels after treatment were similar for
the two groups. However, the percent change in the AT-LDL level was significantly
(P=0.020) lower in the Theracurmin((r)) group compared with the placebo group.
CONCLUSION: Theracurmin((r)) reduced levels of atherosclerotic AT-LDL, which may
lead to the prevention of future cardiovascular events in mild COPD subjects.
PMID- 27616886
TI - The influence of different long-circulating materials on the pharmacokinetics of
liposomal vincristine sulfate.
AB - PURPOSE: This study was designed to improve the in vivo pharmacokinetics of long
circulating vincristine sulfate (VS)-loaded liposomes; three different long
circulating materials, chitosan, poly(ethylene glycol)-1,2-distearoyl sn-glycero
3-phosphatidylethanolamine (PEG-DSPE), and poly(ethylene glycol)-poly-lactide-co
glycolide (PEG-PLGA), were evaluated at the same coating molar ratio with the
commercial product Marqibo((r)) (vincristine sulfate liposome injection [VSLI]).
MATERIALS AND METHODS: VS-loaded liposomes were prepared by a pH gradient method
and were then coated with chitosan, PEG-DSPE, or PEG-PLGA. Physicochemical
properties, including the morphology, particle size, zeta potential,
encapsulation efficiency (EE%), pH, drug loading, and in vitro release, were
determined. Preservation stability and pharmacokinetic studies were performed to
compare the membrane-coated liposomes with either commercially available
liposomes or the VS solution. RESULTS: The sphere-like morphology of the vesicles
was confirmed by transmission electron microscope. Increased particle size,
especially for the chitosan formulation, was observed after the coating process.
However, the EE% was ~99.0% with drug loading at 2.0 mg/mL, which did not change
after the coating process. The coating of long-circulation materials, except for
chitosan, resulted in negatively charged and stable vesicles at physiological pH.
The near-zero zeta potential exhibited by the PEG-DSPE formulation leads to a
longer circulation lifetime and improved absorption for VS, when compared with
the PEG-PLGA formulation. Compared with the commercial product, PEG was
responsible for a higher plasma VS concentration and a longer half-life.
CONCLUSION: PEG-DSPE coating may be related to better absorption, based on the
stability and a pharmacokinetic improvement in the blood circulation time.
PMID- 27616887
TI - An integrated study on antimicrobial activity and ecotoxicity of quantum dots and
quantum dots coated with the antimicrobial peptide indolicidin.
AB - This study attempts to evaluate the antimicrobial activity and the ecotoxicity of
quantum dots (QDs) alone and coated with indolicidin. To meet this objective, we
tested the level of antimicrobial activity on Gram-positive and Gram-negative
bacteria, and we designed an ecotoxicological battery of test systems and
indicators able to detect different effects using a variety of end points. The
antibacterial activity was analyzed against Staphylococcus aureus (ATCC 6538),
Pseudomonas aeruginosa (ATCC 1025), Escherichia coli (ATCC 11229), and Klebsiella
pneumoniae (ATCC 10031), and the results showed an improved germicidal action of
QDs-Ind. Toxicity studies on Daphnia magna indicated a decrease in toxicity for
QDs-Ind compared to QDs alone, lack of bioluminescence inhibition on Vibrio
fisheri, and no mutations in Salmonella typhimurium TA 100. The comet assay and
oxidative stress experiments performed on D. magna showed a genotoxic and an
oxidative damage with a dose-response trend. Indolicidin retained its activity
when bound to QDs. We observed an enhanced activity for QDs-Ind. The presence of
indolicidin on the surface of QDs was able to decrease its QDs toxicity.
PMID- 27616888
TI - Diffusion tensor imaging in the characterization of multiple system atrophy.
AB - PURPOSE: Multiple system atrophy (MSA) is a rare neurodegenerative disease that
remains poorly understood, and the diagnosis of MSA continues to be challenging.
We endeavored to improve the diagnostic process and understanding of in vivo
characteristics of MSA by diffusion tensor imaging (DTI). MATERIALS AND METHODS:
Twenty MSA subjects, ten parkinsonian dominant (MSA-P), ten cerebellar dominant
(MSA-C), and 20 healthy volunteer subjects were recruited. Fractional anisotropy,
mean diffusivity, radial diffusivity, and axial diffusivity maps were processed
using tract-based spatial statistics. Diffusion data were additionally evaluated
in the basal ganglia. A support vector machine was used to assess diagnostic
utility, leave-one-out cross-validation in the evaluation of classification
schemes, and receiver operating characteristic analyses to determine cutoff
values. RESULTS: We detected widespread changes in the brain white matter of MSA
subjects; however, no group-wise differences were found between MSA-C and MSA-P
subgroups. Altered DTI metrics in the putamen and middle cerebellar peduncles
were associated with a positive parkinsonian and cerebellar phenotype,
respectively. Concerning clinical applicability, we achieved high classification
performance on mean diffusivity data in the combined bilateral putamen and middle
cerebellar peduncle (accuracy 90.3%+/-9%, sensitivity 86.5%+/-11%, and
specificity 99.3%+/-4%). CONCLUSION: DTI in the middle cerebellar peduncle and
putamen may be used in the diagnosis of MSA with a high degree of accuracy.
PMID- 27616889
TI - Attributes of innovations and approaches to scalability - lessons from a national
program to extend the scope of practice of health professionals.
AB - The context for the paper was the evaluation of a national program in Australia
to investigate extended scopes of practice for health professionals (paramedics,
physiotherapists, and nurses). The design of the evaluation involved a mixed
methods approach with multiple data sources. Four multidisciplinary models of
extended scope of practice were tested over an 18-month period, involving 26
organizations, 224 health professionals, and 36 implementation sites. The
evaluation focused on what could be learned to inform scaling up the extended
scopes of practice on a national scale. The evaluation findings were used to
develop a conceptual framework for use by clinicians, managers, and policy makers
to determine appropriate strategies for scaling up effective innovations.
Development of the framework was informed by the literature on the diffusion of
innovations, particularly an understanding that certain attributes of innovations
influence adoption. The framework recognizes the role played by three groups of
stakeholders: evidence producers, evidence influencers, and evidence adopters.
The use of the framework is illustrated with four case studies from the
evaluation. The findings demonstrate how the scaling up of innovations can be
influenced by three quite distinct approaches - letting adoption take place in an
uncontrolled, unplanned, way; actively helping the process of adoption; or taking
deliberate steps to ensure that adoption takes place. Development of the
conceptual framework resulted in two sets of questions to guide decisions about
scalability, one for those considering whether to adopt the innovation (evidence
adopters), and the other for those trying to decide on the optimal strategy for
dissemination (evidence influencers).
PMID- 27616890
TI - The clinicopathological significance of RUNX3 hypermethylation and mRNA
expression in human breast cancer, a meta-analysis.
AB - Aberrant promoter methylation of RUNX3 has been reported in several tumors
including human breast cancer (BC). However, the association between RUNX3
hypermethylation and incidence of BC remains elusive. In this study, a detailed
literature search was performed in Medline and Google Scholar for related
research publications. Analysis of pooled data were executed. Odds ratios with
corresponding confidence intervals were determined and summarized, respectively.
Finally, 13 studies were identified for the meta-analysis. Analysis of the pooled
data showed that RUNX3 hypermethylation was significantly higher in both ductal
carcinoma in situ and invasive ductal carcinoma (IDC) than in normal breast
tissues. In addition, RUNX3 methylation was significantly higher in IDC than in
benign tumor. However, RUNX3 methylation was not significantly higher in IDC than
in ductal carcinoma in situ. We also determined that RUNX3 hypermethylation was
significantly higher in ER positive BC than in ER negative BC. In addition, high
RUNX3 mRNA expression was found to be correlated with better overall survival and
relapse-free survival for all BC patients. Our results strongly support that
RUNX3 hypermethylation may play an important role in BC incidence. RUNX3
methylation is a valuable early biomarker for the diagnosis of BC. Further large
scale studies will provide more insight into the role of RUNX3 hypermethylation
in the carcinogenesis and clinical diagnosis of BC patients.
PMID- 27616891
TI - Historical cohort study examining comparative effectiveness of albuterol inhalers
with and without integrated dose counter for patients with asthma or chronic
obstructive pulmonary disease.
AB - BACKGROUND: Using a metered-dose inhaler (MDI) beyond the labeled number of
actuations may result in inadequate dosing of medication, which can lead to poor
clinical outcomes. This study compared respiratory-related emergency department
(ED) visit rates in patients with asthma, chronic obstructive pulmonary disease,
or both when they used albuterol MDIs with versus without dose counters. METHODS:
This retrospective study used US claims data to identify patients (ages 4-64
years) with asthma, chronic obstructive pulmonary disease, or both, using
albuterol MDIs with or without an integrated dose counter. The study comprised a
1-year baseline period for patient characterization and confounder definition and
a 1-year outcome period following the first albuterol prescription. The primary
end point was the incidence rate of respiratory-related ED visits, compared using
a reduced zero-inflated Poisson regression model. We also compared severe
exacerbation rates and rescue medication use. RESULTS: A total of 93,980 patients
were studied, including 67,251 (72%) in the dose counter cohort and 26,729 (28%)
in the non-dose-counter cohort. The cohorts were broadly similar at baseline
(55,069 [59%] female patients; median age, 37 years). The incidence rate of
respiratory-related ED visits during the outcome year was 45% lower in the dose
counter cohort than in the non-dose-counter cohort (adjusted rate ratio: 0.55;
95% confidence interval: 0.47-0.64). Exacerbation rates and short-acting beta
agonist use were similar between cohorts. CONCLUSION: These findings suggest that
dose counter integration into albuterol MDIs is associated with decreased ED
visit rates. The presence of integrated dose counters on rescue inhalers can help
patients avoid using an empty or near-empty inhaler during exacerbations, thereby
ensuring available medication for relief of their symptoms. Integrated dose
counters on rescue MDIs could represent a simple and effective tool to improve
clinical outcomes during exacerbations, with a potential for cost savings to
health care systems.
PMID- 27616892
TI - Targeting improved patient outcomes using innovative product listing agreements:
a survey of Canadian and international key opinion leaders.
AB - OBJECTIVES: To address the uncertainty associated with procuring pharmaceutical
products, product listing agreements (PLAs) are increasingly being used to
support responsible funding decisions in Canada and elsewhere. These agreements
typically involve financial-based rebating initiatives or, less frequently,
outcome-based contracts. A qualitative survey was conducted to improve the
understanding of outcome-based and more innovative PLAs (IPLAs) based on input
from Canadian and international key opinion leaders in the areas of drug
manufacturing and reimbursement. METHODS: Results from a structured literature
review were used to inform survey development. Potential participants were
invited via email to partake in the survey, which was conducted over phone or in
person. Responses were compiled anonymously for review and reporting. RESULTS:
Twenty-one individuals participated in the survey, including health technology
assessment (HTA) key opinion leaders (38%), pharmaceutical industry chief
executive officers/vice presidents (29%), ex-payers (19%), and current
payers/drug plan managers/HTA (14%). The participants suggested that ~80%-95% of
Canadian PLAs are financial-based rather than outcomes-based. They indicated that
IPLAs offer important benefits to patients, payers, and manufacturers; however,
several challenges limit their use (eg, administrative burden, lack of agreed
upon endpoint). They noted that IPLAs are useful in rapidly evolving therapeutic
areas and those associated with high unmet need, a quantifiable endpoint, and/or
robust data systems. The Canadian Agency for Drugs and Technologies in Health,
the pan-Canadian Pharmaceutical Alliance, and other arms-length organizations
could play important roles in identifying uncertainty and endpoints and brokering
pan-Canadian PLAs. Industry should work collaboratively with payers to identify
uncertainty and develop innovative mechanisms to address it. CONCLUSION: The
survey results indicated that while challenging, use of IPLAs may be associated
with various benefits. Collaboration among stakeholders remains key: Canadian
agencies could play an important role in the success of these agreements, while
industry should be proactive in offering solutions that will help improve
outcomes across the entire health care system.
PMID- 27616893
TI - Prevalence and determinants of metabolic syndrome: a cross-sectional survey of
general medical outpatient clinics using National Cholesterol Education Program
Adult Treatment Panel III criteria in Botswana.
AB - BACKGROUND: Low- and middle-income countries, including Botswana, are facing
rising prevalence of obesity and obesity-related cardiometabolic complications.
Very little information is known about clustering of cardiovascular risk factors
in the outpatient setting during routine visits. We aimed to assess the
prevalence and identify the determinants of metabolic syndrome among the general
outpatients' attendances in Botswana. METHODS: A cross-sectional study was
conducted from August to October 2014 involving outpatients aged >=20 years
without diagnosis of diabetes mellitus. A precoded questionnaire was used to
collect data on participants' sociodemographics, risk factors, and anthropometric
indices. Fasting blood samples were drawn and analyzed for glucose and lipid
profile. Metabolic syndrome was assessed using National Cholesterol Education
Program-Adult Treatment Panel III criteria. RESULTS: In total, 291 participants
were analyzed, of whom 216 (74.2%) were females. The mean age of the total
population was 50.1 (+/-11) years. The overall prevalence of metabolic syndrome
was 27.1% (n=79), with no significant difference between the sexes (female
=29.6%, males =20%, P=0.11). A triad of central obesity, low high-density
lipoprotein-cholesterol, and elevated blood pressure constituted the largest
proportion (38 [13.1%]) of cases of metabolic syndrome, followed by a combination
of low high-density lipoprotein, elevated triglycerides, central obesity, and
elevated blood pressure, with 17 (5.8%) cases. Independent determinants of
metabolic syndrome were antihypertensive use and increased waist circumference.
CONCLUSION: Metabolic syndrome is highly prevalent in the general medical
outpatients clinics. Proactive approaches are needed to screen and manage cases
targeting its most important predictors.
PMID- 27616894
TI - The relationship between emotion regulation capacity, heart rate variability, and
quality of life in individuals with alcohol-related brain damage.
AB - The reliable measurement of quality of life (QoL) presents a challenge in
individuals with alcohol-related brain damage. This study investigated vagally
mediated heart rate variability (vmHRV) as a physiological predictor of QoL. Self
and proxy ratings of QoL and dysexecutive symptoms were collected once, while
vmHRV was repeatedly assessed over a 3-week period at weekly intervals in a
sample of nine alcohol-related brain damaged patients. We provide robustness
checks, bootstrapped correlations with confidence intervals, and standard errors
for mean scores. We observed low to very low heart rate variability scores in our
patients in comparison to norm values found in healthy populations. Proxy ratings
of the QoL scale "subjective physical and mental performance" and everyday
executive dysfunctions were strongly related to vmHRV. Better proxy-rated QoL and
fewer dysexecutive symptoms were observed in those patients with higher vmHRV.
Overall, patients showed low parasympathetic activation favoring the occurrence
of dysfunctional emotion regulation strategies.
PMID- 27616895
TI - Victimization, polyvictimization, and health in Swedish adolescents.
AB - The main objective of this article was to study the relationship between the
different areas of victimization (eg, sexual victimization) and psychological
symptoms, taking into account the full range of victimization domains. The final
aim was to contribute further evidence regarding the bias that studies that focus
on just one area of victimization may be introduced into our psychological
knowledge. The sample included 5,960 second-year high school students in Sweden
with a mean age of 17.3 years (range =16-20 years, standard deviation =0.652), of
which 49.6% were females and 50.4% males. The Juvenile Victimization
Questionnaire and the Trauma Symptom Checklist for Children were used to assess
victimization and psychological problems separately. The results show that a
majority of adolescents have been victimized, females reported more total events
and more sexual victimization and childhood maltreatment, and males were more
often victims of conventional crime. The majority of victimization domains as
well as the sheer number of events (polyvictimization [PV]) proved to be harmful
to adolescent health, affecting females more than males. PV explained part of the
health effect and had an impact on its own and in relation to each domain. This
suggests the possibility that PV to a large degree explains trauma symptoms. In
order to understand the psychological effects of trauma, clinicians and
researchers should take into account the whole range of possible types of
victimization.
PMID- 27616896
TI - Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with
nonalcoholic fatty liver disease.
AB - BACKGROUND: Korean Red Ginseng (KRG) is a well-known natural product with
anticarcinogenic and antioxidant effects. We evaluated the antifatigue effect of
KRG in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Eighty
patients with NAFLD were prospectively randomized to receive 3 wk of KRG or
placebo in addition to counseling on healthy eating and regular exercise. Liver
function test, proinflammatory cytokines, adiponectin, antioxidant activity, and
fatigue score were measured and compared according to the body mass index between
the KRG and placebo groups. RESULTS: The liver function tests were significantly
improved after 3 wk of treatment in both groups. The mean levels (at baseline and
after treatment) of tumor necrosis factor-alpha were 108.0 pg/mL +/- 54.8 pg/mL
and 92.7 pg/mL +/- 39.0 pg/mL (p = 0.018) in the KRG group and 123.1 pg/mL +/-
42.1 pg/mL and 127.5 pg/mL +/- 62.2 pg/mL (p = 0.694) in the placebo group,
respectively. There was a significant difference in change of adiponectin levels
between the KRG (7,751.2 pg/mL +/- 3,108.1 pg/mL and 8,197.3 pg/mL +/- 2,714.5
pg/mL) and placebo groups (7,711.6 pg/mL +/- 3,041.3 pg/mL and 7,286.1 pg/mL +/-
5,188.7 pg/mL, p = 0.027). In patients with overweight, the fatigue score was
significantly decreased in the KRG group (35.0 +/- 13.2 and 24.5 +/- 8.9, p =
0.019). CONCLUSION: Our results show that KRG might be effective in reducing
proinflammatory cytokine and fatigue in overweight patients with NAFLD, in
addition to improvements in adiponectin levels.
PMID- 27616897
TI - Rapid separation and identification of 31 major saponins in Shizhu ginseng by
ultra-high performance liquid chromatography-electron spray ionization-MS/MS.
AB - BACKGROUND: Among the various ginseng strains, Shizhu ginseng is endemic to
China, mainly distributed in Kuandian Manchu Autonomous County (Liaoning
Province, China); however, not much is known about the compounds (especially
saponins) in Shizhu ginseng. METHODS: A rapid, sensitive, and reliable ultra-high
performance liquid chromatography coupled with MS/MS (UHPLC-MS/MS) method was
developed to separate and identify saponins in Shizhu ginseng. RESULTS: The
separation was carried out on a Waters ACQUITY UPLC BEH C18 column (100 mm * 2.1
mm, 1.7 MUm) with acetonitrile and 0.1% formic acid aqueous solution as the
mobile phase under a gradient elution at 40 degrees C. The detection was
performed on a Micromass Quattro Micro API mass spectrometer equipped with
electrospray ionization source in both positive and negative modes. Under the
optimized conditions, a total of 31 saponins were identified or tentatively
characterized by comparing retention time and MS data with related literatures
and reference substances. CONCLUSION: The developed UHPLC-MS/MS method was
suitable for identifying and characterizing the chemical constituents in Shizhu
ginseng, which provided a helpful chemical basis for further research on Shizhu
ginseng.
PMID- 27616898
TI - Effect of Korean Red Ginseng extraction conditions on antioxidant activity,
extraction yield, and ginsenoside Rg1 and phenolic content: optimization using
response surface methodology.
AB - BACKGROUND: Extraction conditions greatly affect composition, as well as
biological activity. Therefore, optimization is essential for maximum efficacy.
METHODS: Korean Red Ginseng (KRG) was extracted under different conditions and
antioxidant activity, extraction yield, and ginsenoside Rg1 and phenolic content
evaluated. Optimized extraction conditions were suggested using response surface
methodology for maximum antioxidant activity and extraction yield. RESULTS:
Analysis of KRG extraction conditions using response surface methodology showed a
good fit of experimental data as demonstrated by regression analysis. Among
extraction factors, such as extraction solvent and extraction time and
temperature, ethanol concentration greatly affected antioxidant activity,
extraction yield, and ginsenoside Rg1 and phenolic content. The optimal
conditions for maximum antioxidant activity and extraction yield were an ethanol
concentration of 48.8%, an extraction time 73.3 min, and an extraction
temperature of 90 degrees C. The antioxidant activity and extraction yield under
optimal conditions were 43.7% and 23.2% of dried KRG, respectively. CONCLUSION:
Ethanol concentration is an important extraction factor for KRG antioxidant
activity and extraction yield. Optimized extraction conditions provide useful
economic advantages in KRG development for functional products.
PMID- 27616899
TI - Antihypertensive effect of Korean Red Ginseng by enrichment of ginsenoside Rg3
and arginine-fructose.
AB - BACKGROUND: Ginsenoside Rg3 and arginine-fructose (Arg-Fru) are known as the
hypotensive compounds of Panax ginseng; however, their efficacy on
antihypertension has not been reported yet to our best knowledge. Thus,
hypotensive components-enriched fraction of red ginseng (HCEF-RG) was prepared
from fine root concentrate (FR) and their antihypertensive effects were
investigated in spontaneously hypertensive rats (SHR). METHODS: Male SHRs were
divided into six groups: control (Wistar Kyoto, SHR); FR 500; FR 1,000; HCEF-RG
500; and HCEF-RG 1,000; samples (mg/kg body weight) were orally administered
every day for 8 wk. Blood pressure was monitored at 1 wk, 2 wk, 3 wk, 4 wk, 6 wk,
and 8 wk by tail cuff method. At 8 wk after samples administration, mice were
killed for the measurement of renin activity (RA), angiotensin-I converting
enzyme inhibition, angiotensin II, and nitric oxide (NO) levels in plasma.
RESULTS: HCEF-RG with four-fold more Rg3 and 24-fold more Arg-Fru contents was
successfully prepared from reacted mixtures of FR and persimmon vinegar (12 times
against FR, v/v) at 80 degrees C for 18 h. Both FR 1,000 and HCEF-RG 1,000 showed
lowered systolic blood pressure than SHR control group and HCEF-RG 1,000 group
exhibited a significant decrease in diastolic blood pressure. RA was
significantly lowered in all treated groups, while angiotensin II did not affect
by FR and HCEF-RG treatment. However, angiotensin-I converting enzyme inhibition
and NO in FR 1,000 and HCEF-RG 1,000 were significantly increased compared with
SHR control group. CONCLUSION: HCEF-RG is more effective and useful for
alleviating hypertension than FR, implying the health benefit of Rg3 and Arg-Fru.
PMID- 27616900
TI - Complete (1)H-NMR and (13)C-NMR spectral assignment of five malonyl ginsenosides
from the fresh flower buds of Panax ginseng.
AB - BACKGROUND: Ginsenosides are the major effective ingredients responsible for the
pharmacological effects of ginseng. Malonyl ginsenosides are natural ginsenosides
that contain a malonyl group attached to a glucose unit of the corresponding
neutral ginsenosides. METHODS: Medium-pressure liquid chromatography and
semipreparative high-performance liquid chromatography were used to isolate
purified compounds and their structures determined by extensive one-dimensional-
and two-dimensional nuclear magnetic resonance (NMR) experiments. RESULTS: A new
saponin, namely malonyl-ginsenoside Re, was isolated from the fresh flower buds
of Panax ginseng, along with malonyl-ginsenosides Rb1, Rb2, Rc, Rd. Some
assignments for previously published (1)H- and (13)C-NMR spectra were found to be
inaccurate. CONCLUSION: This study reports the complete NMR assignment of malonyl
ginsenoside Re, Rb1, Rb2, Rc, and Rd for the first time.
PMID- 27616902
TI - A single-center, randomized, double-blind, placebo-controlled study on the
efficacy and safety of "enzyme-treated red ginseng powder complex (BG11001)" for
antiwrinkle and proelasticity in individuals with healthy skin.
AB - BACKGROUND: During the aging process, skin shows visible changes, characterized
by a loss of elasticity and the appearance of wrinkles due to reduced collagen
production and decreased elasticity of elastin fibers. Panax ginseng Meyer has
been used as a traditional medicine for various diseases due to its wide range of
biological activities including skin protective effects. Ginsenosides are the
main components responsible for the biological activities of ginseng. However,
the protective activities of an enzymatic preparation of red ginseng against
human skin aging have not been investigated. METHODS: The efficacy of an enzyme
treated powder complex of red ginseng (BG11001) in preventing human skin aging
was evaluated by oral administration to 78 randomized individuals. All patients
were requested to take three daily capsules containing either 750 mg of BG11001
or a placebo vehicle for 24 wk; at the end of the testing period, skin roughness,
elasticity, and skin water content were measured. RESULTS: BG11001 significantly
reduced the average roughness of eye wrinkles and the Global Photo Damage Score
compared with the placebo, although there were no significant differences in
arithmetic roughness average between the groups. In addition, gross elasticity
and net elasticity values increased, and transepidermal water loss level
decreased, indicating improved skin elasticity and moisture content. CONCLUSION:
In conclusion, enzyme-treated red ginseng extract significantly improved eye
wrinkle roughness, skin elasticity, and moisture content. Moreover, enzyme
treated red ginseng extract would be useful substance as a bio-health skin care
product.
PMID- 27616901
TI - Effects of Panax ginseng, zearalenol, and estradiol on sperm function.
AB - BACKGROUND: Estrogen signaling pathways are modulated by exogenous factors. Panax
ginseng exerts multiple activities in biological systems and is classified as an
adaptogen. Zearalenol is a potent mycoestrogen that may be present in herbs and
crops arising from contamination or endophytic association. The goal of this
study was to investigate the impact of P. ginseng, zearalenol and estradiol in
tests on spermatozoal function. METHODS: The affinity of these compounds for
estrogen receptor (ER)-alpha and beta (ERalpha and ERbeta)-was assessed in
receptor binding assays. Functional tests on boar spermatozoa motility, movement
and kinematic parameters were conducted using a computer-assisted sperm analyzer.
Tests for capacitation, acrosome reaction (AR), and chromatin decondensation in
spermatozoa were performed using microscopic analysis. RESULTS: Zearalenol-but
not estradiol (E2)- or ginseng-treated spermatozoa-decreased the percentage of
overall, progressive, and rapid motile cells. Zearalenol also decreased
spontaneous AR and increased chromatin decondensation. Ginseng decreased
chromatin decondensation in response to calcium ionophore and decreased AR in
response to progesterone (P4) and ionophore. CONCLUSION: Zearalenol has adverse
effects on sperm motility and function by targeting multiple signaling cascades,
including P4, E2, and calcium pathways. Ginseng protects against chromatin damage
and thus may be beneficial to reproductive fitness.
PMID- 27616903
TI - Ginseng consumption and risk of cancer: A meta-analysis.
AB - BACKGROUND: The findings of currently available studies are not consistent with
regard to the association between the risk of cancer and ginseng consumption.
Therefore, we aimed to evaluate this association by conducting a meta-analysis of
different studies. METHODS: To systematically evaluate the effect of ginseng
consumption on cancer incidence, six databases were searched, including PubMed,
Ovid Technologies, Embase, The Cochrane Library, China National Knowledge
Infrastructure, and Chinese VIP Information, from 1990 to 2014. Statistical
analyses based on the protocol employed for a systematic review were conducted to
calculate the summary relative risks (RRs) and 95% confidence intervals (CIs).
RESULTS: We identified nine studies, including five cohort studies, three case
control studies, and one randomized controlled trial, evaluating the association
between ginseng consumption and cancer risk; these studies involved 7,436 cases
and 334,544 participants. The data from the meta-analysis indicated a significant
16% lower risk of developing cancer in patients who consumed ginseng (RR = 0.84,
95% CI = 0.76-0.92), with evidence of heterogeneity (p = 0.0007, I (2) = 70%).
Stratified analyses suggested that the significant heterogeneity may result from
the incidence data for gastric cancer that were included in this study.
Publication bias also showed the same result as the stratified analyses. In
addition, subgroup analyses for four specific types of cancer (colorectal cancer,
lung cancer, gastric cancer, and liver cancer) were also performed. The summary
RRs for ginseng intake versus no ginseng consumption were 0.77 for lung cancer,
0.83 for gastric cancer, 0.81 for liver cancer, and 0.77 for colorectal cancer.
CONCLUSION: The findings of this meta-analysis indicated that ginseng consumption
is associated with a significantly decreased risk of cancer and that the effect
is not organ specific.
PMID- 27616904
TI - Proteomic analysis reveals that the protective effects of ginsenoside Rb1 are
associated with the actin cytoskeleton in beta-amyloid-treated neuronal cells.
AB - BACKGROUND: The ginsenoside Rb1 (Rb1) is the most abundant compound in the root
of Panax ginseng. Recent studies have shown that Rb1 has a neuroprotective
effect. However, the mechanisms underlying this effect are still unknown.
METHODS: We used stable isotope labeling with amino acids in cell culture,
combined with quantitative mass spectrometry, to explore a potential protective
mechanism of Rb1 in beta-amyloid-treated neuronal cells. RESULTS: A total of
1,231 proteins were commonly identified from three replicate experiments. Among
these, 40 proteins were significantly changed in response to Rb1 pretreatment in
beta-amyloid-treated neuronal cells. Analysis of the functional enrichments and
protein interactions of altered proteins revealed that actin cytoskeleton
proteins might be linked to the regulatory mechanisms of Rb1. The CAP1, CAPZB,
TOMM40, and DSTN proteins showed potential as molecular target proteins for the
functional contribution of Rb1 in Alzheimer's disease (AD). CONCLUSION: Our
proteomic data may provide new insights into the protective mechanisms of Rb1 in
AD.
PMID- 27616905
TI - Total ginsenosides suppress monocrotaline-induced pulmonary hypertension in rats:
involvement of nitric oxide and mitogen-activated protein kinase pathways.
AB - BACKGROUND: Ginsenosides have been shown to exert beneficial pharmacological
effects on the central nervous, cardiovascular, and endocrine systems. We sought
to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced
pulmonary hypertension and to elucidate the underlying mechanism. METHODS: MCT
intoxicated rats were treated with gradient doses of TG, with or without N (G)
nitro-l-arginine methyl ester. The levels of molecules involving the regulation
of nitric oxide and mitogen-activated protein kinase pathways were determined.
RESULTS: TG ameliorated MCT-induced pulmonary hypertension in a dose-dependent
manner, as assessed by the right ventricular systolic pressure, the right
ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG
increased the levels of pulmonary nitric oxide, endothelial nitric oxide
synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen
activated protein kinase phosphatase-1 expression and promoted the
dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38
mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2. CONCLUSION:
TG attenuates MCT-induced pulmonary hypertension, which may involve in part the
regulation of nitric oxide and mitogen-activated protein kinase pathways.
PMID- 27616906
TI - Canola oil is an excellent vehicle for eliminating pesticide residues in aqueous
ginseng extract.
AB - BACKGROUND: We previously reported that two-phase partition chromatography
between ginseng water extract and soybean oil efficiently eliminated pesticide
residues. However, an undesirable odor and an unpalatable taste unique to soybean
oil were two major disadvantages of the method. This study was carried out to
find an alternative vegetable oil that is cost effective, labor effective, and
efficient without leaving an undesirable taste and smell. METHODS: We employed
six vegetable oils that were available at a grocery store. A 1-mL sample of the
corresponding oil containing a total of 32 pesticides, representing four
categories, was mixed with 10% aqueous ginseng extract (20 mL) and equivalent
vegetable oil (7 mL) in Falcon tubes. The final concentration of the pesticides
in the mixture (28 mL) was adjusted to approximately 2 ppm. In addition,
pesticides for spiking were clustered depending on the analytical equipment
(GC/HPLC), detection mode (electron capture detector/nitrogen-phosphorus
detector), or retention time used. Samples were harvested and subjected to
quantitative analysis of the pesticides. RESULTS: Soybean oil demonstrated the
highest efficiency in partitioning pesticide residues in the ginseng extract to
the oil phase. However, canola oil gave the best result in an organoleptic test
due to the lack of undesirable odor and unpalatable taste. Furthermore, the
qualitative and quantitative changes of ginsenosides evaluated by TLC and HPLC,
respectively, revealed no notable change before or after canola oil treatment.
CONCLUSION: We suggest that canola oil is an excellent vehicle with respect to
its organoleptic property, cost-effectiveness and efficiency of eliminating
pesticide residues in ginseng extract.
PMID- 27616907
TI - Modification of ginsenoside composition in red ginseng (Panax ginseng) by
ultrasonication.
AB - The result of USRG-12 indicated that ultrasonication-processed (100 degrees C, 12
h) red ginseng extracts had the highest amount of ginsenosides Rg3 (0.803%), Rg5
(0.167%), and Rk1 (0.175%).
PMID- 27616908
TI - Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces.
AB - BACKGROUND: Joboksansam, Korean bird wild ginseng, is an artificially cultivated
wild ginseng germinated from bird feces. Although numerous pharmacologic
activities of wild ginsengs have been reported, the beneficial effect of
joboksansam in cancer has not been elucidated. In this study, we investigated the
in vivo and in vitro anticancer activities of joboksansam powder. METHODS: To
evaluate the in vivo anticancer activity of joboksansam, we established a
xenograft mouse model bearing RMA cell-derived cancer. Direct cytotoxicity
induced by joboksansam powder was also investigated in vitro using (3-4-5
dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. The inhibitory
activity of this powder on the activation of cell survival signaling involving
Akt and Src was examined with immunoblot analysis. RESULTS: Joboksansam powder
displayed strong inhibitory activity against the increased tumor size, increased
weight of total body and cancer tissues, and mortality of tumor-bearing mice.
Joboksansam powder also suppressed the activation of survival regulatory enzymes
Akt and Src, as assessed by phosphorylation levels in the immunoblot analysis of
tumor tissues. Interestingly, the viability of RMA cells in vitro was directly
decreased by joboksansam treatment. CONCLUSION: Overall, our results strongly
suggest that joboksansam powder has the potential to protect against cancer
generation by direct cytotoxic effects on cancer cells resulting from suppression
of cell survival signaling.
PMID- 27616910
TI - Folded isometric deformations and banana-shaped seedpod.
AB - Thin vegetal shells have recently been a significant source of inspiration for
the design of smart materials and soft actuators. Herein is presented a novel
analytical family of isometric deformations with a family of theta-folds crossing
a family of parallel z-folds; it contains the isometric deformations of a banana
shaped surface inspired by a seedpod, which converts a vertical closing into
either an horizontal closing or an opening depending on the location of the fold.
Similarly to the seedpod, optimum shapes for opening ease are the most elongated
ones.
PMID- 27616909
TI - Safety and efficacy of Ahmed glaucoma valve implantation in refractory glaucomas
in Northern Indian eyes.
AB - PURPOSE: To evaluate the safety and efficacy of Ahmed glaucoma valve (AGV)
implantation in refractory glaucoma in Northern Indian eyes. BACKGROUND: The
success rate of trabeculectomy remains low in cases of refractory glaucoma even
with the use of antifibrotics. Glaucoma drainage devices have proven to be more
efficacious in reducing intraocular pressure (IOP) in these glaucomas. METHODS:
Retrospective records of 55 consecutive patients who underwent AGV implantation
at Dr. Shroff's Charity Eye Hospital, New Delhi, India from January 2003 to
December 2012 were reviewed. Pre-operative data included age, gender, eye
laterality, specific diagnosis, number of anti-glaucoma medications, number of
prior incisional surgeries, visual acuity and IOP on medical treatment.
Postoperative data included visual acuity and IOP on day one, 1 week, 1 month, 3
months, 6 months, 1 year and yearly thereafter, number of anti-glaucoma
medications, any complication or additional surgical intervention required.
Success was defined as IOP >5 and <22 mmHg with or without treatment. RESULTS:
Mean IOP decreased from 39.71 +/- 8.99 pre-operatively to 17.52 +/- 5.72 mmHg at
last follow-up (p < 0.001) and number of medications reduced from 3.27 +/- 0.84
to 1.25 +/- 0.88 (p < 0.001). Visual acuity remained within one Snellen line or
improved at last follow-up in 47 cases (85.4%). The cumulative probability of
success was 85.45% at 1 year and 79.63% at 3 years. The incidence of post
operative complications was 25.45%. CONCLUSION: AGV implantation has proven to be
safe and is effective in controlling IOP in refractory glaucoma in Northern
Indian eyes.
PMID- 27616911
TI - Gasification reactor engineering approach to understanding the formation of
biochar properties.
AB - The correlation between thermochemical provenance and biochar functionality is
poorly understood. To this end, operational reactor temperatures (spanning the
reduction zone), pressure and product gas composition measurements were obtained
from a downdraft gasifier and compared against elemental composition, surface
morphology and polyaromatic hydrocarbon content (PAH) of the char produced. Pine
feedstock moisture with values of 7% and 17% was the experimental variable.
Moderately high steady-state temperatures were observed inside the reactor, with
a ca 50 degrees C difference in how the gasifier operated between the two
feedstock types. Both chars exhibited surface properties comparable to activated
carbon, but the relatively small differences in temperature caused significant
variations in biochar surface area and morphology: micropore area 584 against 360
m2 g-1, and micropore volume 0.287 against 0.172 cm3 g-1. Differences in char
extractable PAH content were also observed, with higher concentrations (187 ug g
1 +/- 18 compared with 89 +/- 19 ug g-1 Sigma16EPA PAH) when the gasifier was
operated with higher moisture content feedstock. It is recommended that greater
detail on operational conditions during biochar production should be incorporated
to future biochar characterization research as a consequence of these results.
PMID- 27616912
TI - Three-dimensional water impact at normal incidence to a blunt structure.
AB - The three-dimensional water impact onto a blunt structure with a spreading
rectangular contact region is studied. The structure is mounted on a flat rigid
plane with the impermeable curved surface of the structure perpendicular to the
plane. Before impact, the water region is a rectangular domain of finite
thickness bounded from below by the rigid plane and above by the flat free
surface. The front free surface of the water region is vertical, representing the
front of an advancing steep wave. The water region is initially advancing towards
the structure at a constant uniform speed. We are concerned with the slamming
loads acting on the surface of the structure during the initial stage of water
impact. Air, gravity and surface tension are neglected. The problem is analysed
by using some ideas of pressure-impulse theory, but including the time-dependence
of the wetted area of the structure. The flow caused by the impact is three
dimensional and incompressible. The distribution of the pressure-impulse (the
time-integral of pressure) over the surface of the structure is analysed and
compared with the distributions provided by strip theories. The total impulse
exerted on the structure during the impact stage is evaluated and compared with
numerical and experimental predictions. An example calculation is presented of
water impact onto a vertical rigid cylinder. Three-dimensional effects on the
slamming loads are the main concern in this study.
PMID- 27616913
TI - Discrete dislocation plasticity analysis of loading rate-dependent static
friction.
AB - From a microscopic point of view, the frictional force associated with the
relative sliding of rough surfaces originates from deformation of the material in
contact, by adhesion in the contact interface or both. We know that plastic
deformation at the size scale of micrometres is not only dependent on the size of
the contact, but also on the rate of deformation. Moreover, depending on its
physical origin, adhesion can also be size and rate dependent, albeit different
from plasticity. We present a two-dimensional model that incorporates both
discrete dislocation plasticity inside a face-centred cubic crystal and adhesion
in the interface to understand the rate dependence of friction caused by
micrometre-size asperities. The friction strength is the outcome of the
competition between adhesion and discrete dislocation plasticity. As a function
of contact size, the friction strength contains two plateaus: at small contact
length [Formula: see text], the onset of sliding is fully controlled by adhesion
while for large contact length [Formula: see text], the friction strength
approaches the size-independent plastic shear yield strength. The transition
regime at intermediate contact size is a result of partial de-cohesion and size
dependent dislocation plasticity, and is determined by dislocation properties,
interfacial properties as well as by the loading rate.
PMID- 27616914
TI - Constructor theory of probability.
AB - Unitary quantum theory, having no Born Rule, is non-probabilistic. Hence the
notorious problem of reconciling it with the unpredictability and appearance of
stochasticity in quantum measurements. Generalizing and improving upon the so
called 'decision-theoretic approach', I shall recast that problem in the recently
proposed constructor theory of information-where quantum theory is represented as
one of a class of superinformation theories, which are local, non-probabilistic
theories conforming to certain constructor-theoretic conditions. I prove that the
unpredictability of measurement outcomes (to which constructor theory gives an
exact meaning) necessarily arises in superinformation theories. Then I explain
how the appearance of stochasticity in (finitely many) repeated measurements can
arise under superinformation theories. And I establish sufficient conditions for
a superinformation theory to inform decisions (made under it) as if it were
probabilistic, via a Deutsch-Wallace-type argument-thus defining a class of
decision-supporting superinformation theories. This broadens the domain of
applicability of that argument to cover constructor-theory compliant theories. In
addition, in this version some of the argument's assumptions, previously
construed as merely decision-theoretic, follow from physical properties expressed
by constructor-theoretic principles.
PMID- 27616915
TI - N-body dynamics on closed surfaces: the axioms of mechanics.
AB - A major challenge for our understanding of the mathematical basis of particle
dynamics is the formulation of N-body and N-vortex dynamics on Riemann surfaces.
In this paper, we show how the two problems are, in fact, closely related when
considering the role played by the intrinsic geometry of the surface. This
enables a straightforward deduction of the dynamics of point masses, using
recently derived results for point vortices on general closed differentiable
surfaces M endowed with a metric g. We find, generally, that Kepler's Laws do not
hold. What is more, even Newton's First Law (the law of inertia) fails on closed
surfaces with variable curvature (e.g. the ellipsoid).
PMID- 27616916
TI - Two-scale homogenization to determine effective parameters of thin metallic
structured films.
AB - We present a homogenization method based on matched asymptotic expansion
technique to derive effective transmission conditions of thin structured films.
The method leads unambiguously to effective parameters of the interface which
define jump conditions or boundary conditions at an equivalent zero thickness
interface. The homogenized interface model is presented in the context of
electromagnetic waves for metallic inclusions associated with Neumann or
Dirichlet boundary conditions for transverse electric or transverse magnetic wave
polarization. By comparison with full-wave simulations, the model is shown to be
valid for thin interfaces up to thicknesses close to the wavelength. We also
compare our effective conditions with the two-sided impedance conditions obtained
in transmission line theory and to the so-called generalized sheet transition
conditions.
PMID- 27616918
TI - Geophysical fluid dynamics: whence, whither and why?
AB - This article discusses the role of geophysical fluid dynamics (GFD) in
understanding the natural environment, and in particular the dynamics of
atmospheres and oceans on Earth and elsewhere. GFD, as usually understood, is a
branch of the geosciences that deals with fluid dynamics and that, by tradition,
seeks to extract the bare essence of a phenomenon, omitting detail where
possible. The geosciences in general deal with complex interacting systems and in
some ways resemble condensed matter physics or aspects of biology, where we seek
explanations of phenomena at a higher level than simply directly calculating the
interactions of all the constituent parts. That is, we try to develop theories or
make simple models of the behaviour of the system as a whole. However, these days
in many geophysical systems of interest, we can also obtain information for how
the system behaves by almost direct numerical simulation from the governing
equations. The numerical model itself then explicitly predicts the emergent
phenomena-the Gulf Stream, for example-something that is still usually impossible
in biology or condensed matter physics. Such simulations, as manifested, for
example, in complicated general circulation models, have in some ways been
extremely successful and one may reasonably now ask whether understanding a
complex geophysical system is necessary for predicting it. In what follows we
discuss such issues and the roles that GFD has played in the past and will play
in the future.
PMID- 27616917
TI - Modelling modal gating of ion channels with hierarchical Markov models.
AB - Many ion channels spontaneously switch between different levels of activity.
Although this behaviour known as modal gating has been observed for a long time
it is currently not well understood. Despite the fact that appropriately
representing activity changes is essential for accurately capturing time course
data from ion channels, systematic approaches for modelling modal gating are
currently not available. In this paper, we develop a modular approach for
building such a model in an iterative process. First, stochastic switching
between modes and stochastic opening and closing within modes are represented in
separate aggregated Markov models. Second, the continuous-time hierarchical
Markov model, a new modelling framework proposed here, then enables us to combine
these components so that in the integrated model both mode switching as well as
the kinetics within modes are appropriately represented. A mathematical analysis
reveals that the behaviour of the hierarchical Markov model naturally depends on
the properties of its components. We also demonstrate how a hierarchical Markov
model can be parametrized using experimental data and show that it provides a
better representation than a previous model of the same dataset. Because evidence
is increasing that modal gating reflects underlying molecular properties of the
channel protein, it is likely that biophysical processes are better captured by
our new approach than in earlier models.
PMID- 27616919
TI - Correction to 'On the acoustics of an impedance liner with shear and cross flow',
by Campos, Legendre and Sambuc.
PMID- 27616920
TI - Geometric flow control of shear bands by suppression of viscous sliding.
AB - Shear banding is a plastic flow instability with highly undesirable consequences
for metals processing. While band characteristics have been well studied, general
methods to control shear bands are presently lacking. Here, we use high-speed
imaging and micro-marker analysis of flow in cutting to reveal the common
fundamental mechanism underlying shear banding in metals. The flow unfolds in two
distinct phases: an initiation phase followed by a viscous sliding phase in which
most of the straining occurs. We show that the second sliding phase is well
described by a simple model of two identical fluids being sheared across their
interface. The equivalent shear band viscosity computed by fitting the model to
experimental displacement profiles is very close in value to typical liquid metal
viscosities. The observation of similar displacement profiles across different
metals shows that specific microstructure details do not affect the second phase.
This also suggests that the principal role of the initiation phase is to generate
a weak interface that is susceptible to localized deformation. Importantly, by
constraining the sliding phase, we demonstrate a material-agnostic method-passive
geometric flow control-that effects complete band suppression in systems which
otherwise fail via shear banding.
PMID- 27616922
TI - Maximal liquid bridges between horizontal cylinders.
AB - We investigate two-dimensional liquid bridges trapped between pairs of identical
horizontal cylinders. The cylinders support forces owing to surface tension and
hydrostatic pressure that balance the weight of the liquid. The shape of the
liquid bridge is determined by analytically solving the nonlinear Laplace-Young
equation. Parameters that maximize the trapping capacity (defined as the cross
sectional area of the liquid bridge) are then determined. The results show that
these parameters can be approximated with simple relationships when the radius of
the cylinders is small compared with the capillary length. For such small
cylinders, liquid bridges with the largest cross-sectional area occur when the
centre-to-centre distance between the cylinders is approximately twice the
capillary length. The maximum trapping capacity for a pair of cylinders at a
given separation is linearly related to the separation when it is small compared
with the capillary length. The meniscus slope angle of the largest liquid bridge
produced in this regime is also a linear function of the separation. We
additionally derive approximate solutions for the profile of a liquid bridge,
using the linearized Laplace-Young equation. These solutions analytically verify
the above-mentioned relationships obtained for the maximization of the trapping
capacity.
PMID- 27616921
TI - On a possible methodology for identifying the initiation of damage of a class of
polymeric materials.
AB - In this paper, we provide a possible methodology for identifying the initiation
of damage in a class of polymeric solids. Unlike most approaches to damage that
introduce a damage parameter, which might be a scalar, vector or tensor, that
depends on the stress or strain (that requires knowledge of an appropriate
reference configuration in which the body was stress free and/or without any
strain), we exploit knowledge of the fact that damage is invariably a consequence
of the inhomogeneity of the body that makes the body locally 'weak' and the fact
that the material properties of a body invariably depend on the density, among
other variables that can be defined in the current configuration, of the body.
This allows us to use density, for a class of polymeric materials, as a means to
identify incipient damage in the body. The calculations that are carried out for
the biaxial stretch of an inhomogeneous multi-network polymeric solid bears out
the appropriateness of the thesis that the density of the body can be used to
forecast the occurrence of damage, with the predictions of the theory agreeing
well with experimental results. The study also suggests a meaningful damage
criterion for the class of bodies being considered.
PMID- 27616923
TI - Self-similar slip instability on interfaces with rate- and state-dependent
friction.
AB - We examine the development of a frictional instability, with diverging sliding
rate, at the interface of elastic bodies in contact. Evolution of friction is
determined by a slip rate and state dependence. Following Viesca (2016 Phys. Rev.
E93, 060202(R). (doi:10.1103/PhysRevE.93.060202)), we show through an appropriate
change of variable, the existence of blow-up solutions that are fixed points of a
dynamical system. The solutions show self-similarity of the simple variety:
separable dependence of time and space. For an interface with uniform frictional
properties, there is a single-problem parameter. We examine the linear stability
of these fixed points, as this problem parameter is varied. Specifically, we
consider two archetypical elastic settings of the slip surface, in which
interactions between points on the surface are either local or non-local. We show
that, independent of the nature of elastic interactions, the fixed-points lose
stability in the same matter as the parameter is increased towards a limit value:
an apparently infinite sequence of Hopf bifurcations. However, for any value of
the parameter, the nonlinear development of the instability is attraction, if not
asymptotic convergence, towards these fixed points, owing to the existence of
stable eigenmodes. For comparison, we perform numerical solutions of the original
evolution equations and find precise agreement with the results of the analysis.
PMID- 27616924
TI - Anchoring historical sequences using a new source of astro-chronological tie
points.
AB - The discovery of past spikes in atmospheric radiocarbon activity, caused by major
solar energetic particle events, has opened up new possibilities for high
precision chronometry. The two spikes, or Miyake Events, have now been widely
identified in tree-rings that grew in the years 775 and 994 CE. Furthermore, all
other plant material that grew in these years would also have incorporated the
anomalously high concentrations of radiocarbon. Crucially, some plant-based
artefacts, such as papyrus documents, timber beams and linen garments, can also
be allocated to specific positions within long, currently unfixed, historical
sequences. Thus, Miyake Events represent a new source of tie-points that could
provide the means for anchoring early chronologies to the absolute timescale.
Here, we explore this possibility, outlining the most expeditious approaches, the
current challenges and obstacles, and how they might best be overcome.
PMID- 27616925
TI - Cloaking through cancellation of diffusive wave scattering.
AB - A new cloaking mechanism, which makes enclosed objects invisible to diffusive
photon density waves, is proposed. First, diffusive scattering from a basic core
shell geometry, which represents the cloaked structure, is studied. The
conditions of scattering cancellation in a quasi-static scattering regime are
derived. These allow for tailoring the diffusivity constant of the shell
enclosing the object so that the fields scattered from the shell and the object
cancel each other. This means that the photon flow outside the cloak behaves as
if the cloaked object were not present. Diffusive light invisibility may have
potential applications in hiding hot spots in infrared thermography or tissue
imaging.
PMID- 27616926
TI - Modelling of particle-laden flow inside nanomaterials.
AB - In this paper, we demonstrate the usage of the Nernst-Planck equation in
conjunction with mean-field theory to investigate particle-laden flow inside
nanomaterials. Most theoretical studies in molecular encapsulation at the
nanoscale do not take into account any macroscopic flow fields that are crucial
in squeezing molecules into nanostructures. Here, a multi-scale idea is used to
address this issue. The macroscopic transport of gas is described by the Nernst
Planck equation, whereas molecular interactions between gases and between the gas
and the host material are described using a combination of molecular dynamics
simulation and mean-field theory. In particular, we investigate flow-driven
hydrogen storage inside doubly layered graphene sheets and graphene-oxide
frameworks (GOFs). At room temperature and with slow velocity fields, we find
that a single molecular layer is formed almost instantaneously on the inner
surface of the graphene sheets, while molecular ligands between GOFs induce multi
layers. For higher velocities, multi-layers are also formed between graphene. For
even larger velocities, the cavity of graphene is filled entirely with hydrogen,
whereas for GOFs there exist two voids inside each periodic unit. The flow-driven
hydrogen storage inside GOFs with various ligand densities is also investigated.
PMID- 27616927
TI - Asynchronous partial contact motion due to internal resonance in multiple degree
of-freedom rotordynamics.
AB - Sudden onset of violent chattering or whirling rotor-stator contact motion in
rotational machines can cause significant damage in many industrial applications.
It is shown that internal resonance can lead to the onset of bouncing-type
partial contact motion away from primary resonances. These partial contact limit
cycles can involve any two modes of an arbitrarily high degree-of-freedom system,
and can be seen as an extension of a synchronization condition previously
reported for a single disc system. The synchronization formula predicts multiple
drivespeeds, corresponding to different forms of mode-locked bouncing orbits.
These results are backed up by a brute-force bifurcation analysis which reveals
numerical existence of the corresponding family of bouncing orbits at
supercritical drivespeeds, provided the damping is sufficiently low. The numerics
reveal many overlapping families of solutions, which leads to significant multi
stability of the response at given drive speeds. Further, secondary bifurcations
can also occur within each family, altering the nature of the response and
ultimately leading to chaos. It is illustrated how stiffness and damping of the
stator have a large effect on the number and nature of the partial contact
solutions, illustrating the extreme sensitivity that would be observed in
practice.
PMID- 27616928
TI - Wrinkling of a stiff thin film bonded to a pre-strained, compliant substrate with
finite thickness.
AB - A stiff thin film bonded to a pre-strained, compliant substrate wrinkles into a
sinusoidal form upon release of the pre-strain. Many analytical models developed
for the critical pre-strain for wrinkling assume that the substrate is semi
infinite. This critical pre-strain is actually much smaller than that for a
substrate with finite thickness (Ma Y et al. 2016 Adv. Funct. Mater.
(doi:10.1002/adfm.201600713)). An analytical solution of the critical pre-strain
for a system of a stiff film bonded to a pre-strained, finite-thickness,
compliant substrate is obtained, and it agrees well with the finite-element
analysis. The finite-thickness effect is significant when the substrate tensile
stiffness cannot overwhelm the film tensile stiffness.
PMID- 27616929
TI - Optimization and small-amplitude analysis of Purcell's three-link microswimmer
model.
AB - This work studies the motion of Purcell's three-link microswimmer in viscous
flow, by using perturbation expansion of its dynamics under small-amplitude
strokes. Explicit leading-order expressions and next-order correction terms for
the displacement of the swimmer are obtained for the cases of a square or
circular gait in the plane of joint angles. The correction terms demonstrate the
reversal in movement direction for large stroke amplitudes, which has previously
only been shown numerically. In addition, asymptotic expressions for Lighthill's
energetic efficiency are obtained for both gaits. These approximations enable
calculating optimal stroke amplitudes and swimmer's geometry (i.e. ratio of
links' lengths) for maximizing either net displacement or Lighthill's efficiency.
PMID- 27616930
TI - Substructurability: the effect of interface location on a real-time dynamic
substructuring test.
AB - A full-scale experimental test for large and complex structures is not always
achievable. This can be due to many reasons, the most prominent one being the
size limitations of the test. Real-time dynamic substructuring is a hybrid
testing method where part of the system is modelled numerically and the rest of
the system is kept as the physical test specimen. The numerical-physical parts
are connected via actuators and sensors and the interface is controlled by
advanced algorithms to ensure that the tested structure replicates the emulated
system with sufficient accuracy. The main challenge in such a test is to overcome
the dynamic effects of the actuator and associated controller, that inevitably
introduce delay into the substructured system which, in turn, can destabilize the
experiment. To date, most research concentrates on developing control strategies
for stable recreation of the full system when the interface location is given a
priori. Therefore, substructurability is mostly studied in terms of control.
Here, we consider the interface location as a parameter and study its effect on
the stability of the system in the presence of delay due to actuator dynamics and
define substructurability as the system's tolerance to delay in terms of the
different interface locations. It is shown that the interface location has a
major effect on the tolerable delays in an experiment and, therefore, careful
selection of it is necessary.
PMID- 27616931
TI - Vertical ground motion and its effects on liquefaction resistance of fully
saturated sand deposits.
AB - Soil liquefaction has been extensively investigated over the years with the aim
to understand its fundamental mechanism and successfully remediate it. Despite
the multi-directional nature of earthquakes, the vertical seismic component is
largely neglected, as it is traditionally considered to be of much lower
amplitude than the components in the horizontal plane. The 2010-2011 Canterbury
earthquake sequence in New Zealand is a prime example that vertical accelerations
can be of significant magnitude, with peak amplitudes well exceeding their
horizontal counterparts. As research on this topic is very limited, there is an
emerging need for a more thorough investigation of the vertical motion and its
effect on soil liquefaction. As such, throughout this study, uni- and
bidirectional finite-element analyses are carried out focusing on the influence
of the input vertical motion on sand liquefaction. The effects of the frequency
content of the input motion, of the depth of the deposit and of the hydraulic
regime, using variable permeability, are investigated and exhaustively discussed.
The results indicate that the usual assumption of linear elastic response when
compressional waves propagate in a fully saturated sand deposit does not always
hold true. Most importantly post-liquefaction settlements appear to be increased
when the vertical component is included in the analysis.
PMID- 27616932
TI - A micromechanical approach for homogenization of elastic metamaterials with
dynamic microstructure.
AB - An approximate homogenization technique is presented for generally anisotropic
elastic metamaterials consisting of an elastic host material containing randomly
distributed heterogeneities displaying frequency-dependent material properties.
The dynamic response may arise from relaxation processes such as viscoelasticity
or from dynamic microstructure. A Green's function approach is used to model
elastic inhomogeneities embedded within a uniform elastic matrix as force sources
that are excited by a time-varying, spatially uniform displacement field.
Assuming dynamic subwavelength inhomogeneities only interact through their volume
averaged fields implies the macroscopic stress and momentum density fields are
functions of both the microscopic strain and velocity fields, and may be related
to the macroscopic strain and velocity fields through localization tensors. The
macroscopic and microscopic fields are combined to yield a homogenization scheme
that predicts the local effective stiffness, density and coupling tensors for an
effective Willis-type constitutive equation. It is shown that when internal
degrees of freedom of the inhomogeneities are present, Willis-type coupling
becomes necessary on the macroscale. To demonstrate the utility of the
homogenization technique, the effective properties of an isotropic elastic matrix
material containing isotropic and anisotropic spherical inhomogeneities,
isotropic spheroidal inhomogeneities and isotropic dynamic spherical
inhomogeneities are presented and discussed.
PMID- 27616933
TI - Mobius bands, unstretchable material sheets and developable surfaces.
AB - A Mobius band can be formed by bending a sufficiently long rectangular
unstretchable material sheet and joining the two short ends after twisting by 180
degrees . This process can be modelled by an isometric mapping from a rectangular
region to a developable surface in three-dimensional Euclidean space. Attempts
have been made to determine the equilibrium shape of a Mobius band by minimizing
the bending energy in the class of mappings from the rectangular region to the
collection of developable surfaces. In this work, we show that, although a
surface obtained from an isometric mapping of a prescribed planar region must be
developable, a mapping from a prescribed planar region to a developable surface
is not necessarily isometric. Based on this, we demonstrate that the notion of a
rectifying developable cannot be used to describe a pure bending of a rectangular
region into a Mobius band or a generic ribbon, as has been erroneously done in
many publications. Specifically, our analysis shows that the mapping from a
prescribed planar region to a rectifying developable surface is isometric only if
that surface is cylindrical with the midline being the generator. Towards
providing solutions to this issue, we discuss several alternative modelling
strategies that respect the distinction between the physical constraint of
unstretchability and the geometrical notion of developability.
PMID- 27616934
TI - Bidispersive-inclined convection.
AB - A model is presented for thermal convection in an inclined layer of porous
material when the medium has a bidispersive structure. Thus, there are the usual
macropores which are full of a fluid, but there are also a system of micropores
full of the same fluid. The model we employ is a modification of the one proposed
by Nield & Kuznetsov (2006 Int. J. Heat Mass Transf.49, 3068-3074.
(doi:10.1016/j.ijheatmasstransfer.2006.02.008)), although we consider a single
temperature field only.
PMID- 27616935
TI - Comments on the article by A. J. Lecloux (J Nanopart Res (2015) 17:447) regarding
the use of volume-specific surface area (VSSA) to classify nanomaterials.
AB - In November 2015, an article by A. J. Lecloux was published in this journal (J
Nanopart Res, 17:447, 2015). The article focused on the use of volume-specific
surface area (VSSA) for the implementation of the European Commission's
recommended definition of "nanomaterial". In that paper, VSSA values were
calculated for polydisperse particulate materials using a particle number-based
averaging method which do not agree with earlier results of VSSA simulations of
polydisperse materials reported in 2014 by the Joint Research Centre (JRC) of the
European Commission (EC). In this contribution, we explain the difference between
traditional view of VSSA which was used by the JRC and the proposed model of
Lecloux. Through the use of some simple examples for polydisperse materials, it
is demonstrated that the latter produces values which neither correspond to the
generally accepted definition of VSSA nor relate to the commonly used
experimental methods for determining VSSA using gas adsorption. Lecloux's model
therefore does not constitute a basis for practical implementation of the EC's
definition of nanomaterial using gas adsorption techniques.
PMID- 27616936
TI - Evaluation of person-centred care after hip replacement-a controlled before and
after study on the effects of fear of movement and self-efficacy compared to
standard care.
AB - BACKGROUND: The goal of total hip arthroplasty (THA) is optimal pain relief and a
normalized health-related quality of life. Anxious patients describe more pain
and more difficulties than non-anxious patients during rehabilitation after THA.
The aims of the present study were twofold: (1) to identify vulnerable patients
using the general self-efficacy scale (GSES) and the Tampa scale for
Kinesiophobia (TSK), and (2) to evaluate if person-centred care including the
responses of the instruments made rehabilitation more effective in terms of
shortening hospital length of stay. METHODS: The design of the study was quasi
experimental. Patients scheduled for THA, a control group (n = 138) and an
intervention group (n = 128) were consecutively recruited. The intervention was
the provision of person-centred care which was designed to reduce the negative
effects of low self-efficacy and high levels of pain-related fear of movement.
RESULTS: Patients with low GSES in the intervention group had shorter length of
stay (LoS) by 1.6 days (95 % CI 0.16-3.15) p-value 0.03. Patients with high TSK
in the intervention group had shorter LoS by 2.43 days (95 % CI 0.76-4.12) p
value 0.005. For patients who had both, the reduction of LoS was 2.15 days (95 %
CI 0.24-4.04) p-value 0.028. CONCLUSIONS: The GSES and the TSK instrument were
found useful as tools to provide information to support patients which reduced
the LoS by 1.67 days in the whole intervention group (95 % CI 0.72-2.62) p-value
0.001. More importantly, vulnerable patients such as ASA group 3 probably gained
the most from the extra support, they had a reduction with 6.78 days (95 % CI
2.94-10.62) p-value 0.001.
PMID- 27616937
TI - "If you don't take a stand for your life, who will help you?": Men's engagement
in HIV care in KwaZulu-Natal, South Africa.
AB - The needs of South African men with HIV may often be overlooked in the provision
of HIV services, leading to care programs that do not adequately serve the unique
needs of male patients. Additionally, norms of masculinity guide men's behaviors
as they navigate health decision-making and the healthcare systems. The aim of
this study is to examine how masculinity influences healthcare access and
utilization in South Africa, and to identify opportunities for interventions. The
qualitative study took place at one primary health care clinic in a peri-urban
township in KwaZulu-Natal, South Africa. In-depth individual interviews were
conducted with 21 HIV-infected men recruited from the study clinic. Direct
observations of the clinic waiting area were conducted to provide context. Data
were analyzed using a grounded theory-informed approach involving memo writing
and thematic exploration with data coding. On average, participants were 42 years
old and had been on ART for 3.6 years. Participants expressed a range of ways in
which masculine ideals and identity both promoted and inhibited their willingness
and ability to engage in HIV care. Notions of masculinity and social identity
were often directly tied to behaviors influencing care engagement. Such
engagement fostered the reshaping of identity around a novel sense of clinic
advocacy in the face of HIV. Our findings suggested that masculinities are
complex, and are subject to changes and reprioritization in the context of HIV.
Interventions focusing on reframing hegemonic masculinities and initiating
treatment early may have success in bringing more men to the clinic.
PMID- 27616939
TI - Beyond Licking and Grooming: Maternal Regulation of Infant Stress in the Context
of Routine Care.
AB - Rodent epigenetic models of early maternal care have demonstrated that natural
variations in maternal behavior shape the development of stress reactivity and
social behavior in offspring. Rodent models have also revealed the "hidden"
regulatory functions of specific dimensions of maternal behavior. Here we present
research that has extended rodent models of early care to the study of
biobehavioral development in human infants. Research showing contemporaneous and
predictive associations between quality of maternal caregiving behavior (MCB) and
early biobehavioral development is reviewed. New evidence demonstrating the
proximal effects of MCB in early infancy on infant stress reactivity is reported
and highlights the value of examining early parenting at the specific behavioral
level. Future research should extend this domain-specific approach to the study
of infant contributions to the early care environment. Implications for
intervention are discussed.
PMID- 27616940
TI - FABRICATION OF A RETINAL PROSTHETIC TEST DEVICE USING ELECTRODEPOSITED SILICON
OVER POLYPYRROLE PATTERNED WITH SU-8 PHOTORESIST.
AB - A materials fabrication study of a photodiode array for possible application of
retina prosthesis was undertaken. A test device was fabricated using a glassy
carbon electrode patterned with SU-8 photoresist. In the openings, p-type
polypyrrole was first electrodeposited using 1-butyl-1-methylpyridinium
bis(trifluoromethylsulfonyl)imide ionic liquid. The polypyrrole was self-doped
with imide ion at ~1.5 mole %, was verified as p-type, and had a resistivity of
~20 Omegacm. N-type Silicon was then electrodeposited over this layer using
silicon tetrachloride / phosphorus trichloride in acetonitrile and passivated in
a second electrodeposition using trimethylchlorosilane. Electron microscopy
revealed the successful electrodeposition of silicon over patterned polypyrrole.
Rudimentary photodiode behavior was observed. The passivation improved but did
not completely protect the electrodeposited silicon from oxidation by air.
PMID- 27616941
TI - JMFit: A SAS Macro for Joint Models of Longitudinal and Survival Data.
AB - Joint models for longitudinal and survival data now have a long history of being
used in clinical trials or other studies in which the goal is to assess a
treatment effect while accounting for a longitudinal biomarker such as patient
reported outcomes or immune responses. Although software has been developed for
fitting the joint model, no software packages are currently available for
simultaneously fitting the joint model and assessing the fit of the longitudinal
component and the survival component of the model separately as well as the
contribution of the longitudinal data to the fit of the survival model. To
fulfill this need, we develop a SAS macro, called JMFit. JMFit implements a
variety of popular joint models and provides several model assessment measures
including the decomposition of AIC and BIC as well as DeltaAIC and DeltaBIC
recently developed in Zhang et al. (2014). Examples with real and simulated data
are provided to illustrate the use of JMFit.
PMID- 27616942
TI - A Fast and Robust Text Spotter.
AB - We introduce an algorithm for text detection and localization ("spotting") that
is computationally efficient and produces state-of-the-art results. Our system
uses multi-channel MSERs to detect a large number of promising regions, then
subsamples these regions using a clustering approach. Representatives of region
clusters are binarized and then passed on to a deep network. A final line
grouping stage forms word-level segments. On the ICDAR 2011 and 2015 benchmarks,
our algorithm obtains an F-score of 82% and 83%, respectively, at a computational
cost of 1.2 seconds per frame. We also introduce a version that is three times as
fast, with only a slight reduction in performance.
PMID- 27616938
TI - Greater Pupil Size in Response to Emotional Faces as an Early Marker of Social
Communicative Difficulties in Infants at High Risk for Autism.
AB - When scanning faces, individuals with autism spectrum disorder (ASD) have shown
reduced visual attention (e.g., less time on eyes) and atypical autonomic
responses (e.g., heightened arousal). To understand how these differences might
explain sub-clinical variability in social functioning, 9-month-olds, with or
without a family history of ASD, viewed emotionally-expressive faces, and gaze
and pupil diameter (a measure of autonomic activation) were recorded using eye
tracking. Infants at high-risk for ASD with no subsequent clinical diagnosis (HRA
) and low-risk controls (LRC) showed similar face scanning and attention to eyes
and mouth. Attention was overall greater to eyes than mouth, but this varied as a
function of the emotion presented. HRA- showed significantly larger pupil size
than LRC. Correlations between scanning at 9 months, pupil size at 9 months, and
18-month social-communicative behavior, revealed positive associations between
pupil size and attention to both face and eyes at 9 months in LRC, and a negative
association between 9-month pupil size and 18-month social-communicative behavior
in HRA-. The present findings point to heightened autonomic arousal in HRA-.
Further, with greater arousal relating to worse social-communicative functioning
at 18 months, this work points to a mechanism by which unaffected siblings might
develop atypical social behavior.
PMID- 27616943
TI - Suicide risk factors among trans feminine individuals in Lebanon.
AB - Transgender women are disproportionately affected by high rates of depression and
suicide attempts. It is therefore important to identify factors that influence
suicidal risk, particularly in the Middle East where little research has examined
the mental health of transgender women. We examined risk factors associated with
suicide attempts among 54 trans feminine individuals in Beirut, Lebanon. Data
were collected using interviewer-administered questionnaires and analyzed using
bivariate statistics. Twenty-five (46%) participants reported having ever
attempted suicide. Among them, only one participant received some kind of
counseling in response to the attempted suicide. Low general social support, low
social integration, and low support from peers were significantly associated with
a history of attempted suicide, as were being more open about transgender
identity in public and any hormone use (past or current). These findings suggest
that progression in gender transition can have unintended consequences related to
mental health and suicide risk, while social support systems can mitigate the
impact of mental health problems. Some of these findings mirror other contexts
around the globe and can inform mental health services for trans feminine
individuals in Lebanon, the greater Middle East region, and other international
settings.
PMID- 27616944
TI - Counter machines and crystallographic structures.
AB - One way to depict a crystallographic structure is by a periodic (di)graph, i.e.,
a graph whose group of automorphisms has a translational subgroup of finite index
acting freely on the structure. We establish a relationship between periodic
graphs representing crystallographic structures and an infinite hierarchy of
intersection languages ????L d , d = 0, 1, 2, ..., within the intersection
classes of deterministic context-free languages. We introduce a class of counter
machines that accept these languages, where the machines with d counters
recognize the class ????L d An intersection of d languages in ????L1 defines
????L d . We prove that there is a one-to-one correspondence between sets of
walks starting and ending in the same unit of a d-dimensional periodic (di)graph
and the class of languages in ????L d . The proof uses the following result:
given a digraph Delta and a group G, there is a unique digraph Gamma such that G
<= Aut Gamma, G acts freely on the structure, and Gamma/G ? Delta.
PMID- 27616945
TI - Interactive computations: toward risk management in interactive intelligent
systems.
AB - Understanding the nature of interactions is regarded as one of the biggest
challenges in projects related to complex adaptive systems. We discuss
foundations for interactive computations in interactive intelligent systems
(IIS), developed in the Wistech program and used for modeling complex systems. We
emphasize the key role of risk management in problem solving by IIS. The
considerations are based on experience gained in real-life projects concerning,
e.g., medical diagnosis and therapy support, control of an unmanned helicopter,
fraud detection algorithmic trading or fire commander decision support.
PMID- 27616946
TI - A Prospective Validation Study of a Rainbow Model of Integrated Care Measurement
Tool in Singapore.
AB - INTRODUCTION: The conceptual ambiguity of the integrated care concept precludes a
full understanding of what constitutes a well-integrated health system, posing a
significant challenge in measuring the level of integrated care. Most available
measures have been developed from a disease-specific perspective and only measure
certain aspects of integrated care. Based on the Rainbow Model of Integrated
Care, which provides a detailed description of the complex concept of integrated
care, a measurement tool has been developed to assess integrated care within a
care system as a whole gathered from healthcare providers' and managerial
perspectives. This paper describes the methodology of a study seeking to validate
the Rainbow Model of Integrated Care measurement tool within and across the
Singapore Regional Health System. The Singapore Regional Health System is a
recent national strategy developed to provide a better-integrated health system
to deliver seamless and person-focused care to patients through a network of
providers within a specified geographical region. METHODS: The validation process
includes the assessment of the content of the measure and its psychometric
properties. CONCLUSION: If the measure is deemed to be valid, the study will
provide the first opportunity to measure integrated care within Singapore
Regional Health System with the results allowing insights in making
recommendations for improving the Regional Health System and supporting
international comparison.
PMID- 27616947
TI - Values and Principles of Integrated Care.
PMID- 27616948
TI - Interorganisational Integration: Healthcare Professionals' Perspectives on
Barriers and Facilitators within the Danish Healthcare System.
AB - INTRODUCTION: Despite many initiatives to improve coordination of patient
pathways and intersectoral cooperation, Danish health care is still fragmented,
lacking intra- and interorganisational integration. This study explores barriers
to and facilitators of interorganisational integration as perceived by healthcare
professionals caring for patients with chronic obstructive pulmonary disease
within the Danish healthcare system. METHODS: Seven focus groups were conducted
in January through July 2014 with 21 informants from general practice, local
healthcare centres and a pulmonary department at a university hospital in the
Capital Region of Denmark. RESULTS AND DISCUSSION: Our results can be grouped
into five influencing areas for interorganisational integration:
communication/information transfer, committed leadership, patient engagement, the
role and competencies of the general practitioner and organisational culture.
Proposed solutions to barriers in each area hold the potential to improve care
integration as experienced by individuals responsible for supporting and
facilitating it. Barriers and facilitators to integrating care relate to
clinical, professional, functional and normative integration. Especially,
clinical, functional and normative integration seems fundamental to developing
integrated care in practice from the perspective of healthcare professionals.
PMID- 27616949
TI - The Association between Freedom of Choice and Effectiveness of Home Care
Services.
AB - OBJECTIVES: The aim of this paper is to study home care clients' freedom to
choose their services, as well the association between the effectiveness of home
care services and freedom of choice, among other factors. METHODS: A structured
postal survey was conducted among regular home care clients (n = 2096) aged 65 or
older in three towns in Finland. Freedom of choice was studied based on clients'
subjective experiences. The effectiveness of the services was evaluated by means
of changes in the social-care-related quality of life. Regression analyses were
used to test associations. RESULTS: As much as 62% of home care recipients
reported having some choice regarding their services. Choosing meals and visiting
times for the care worker were associated with better effectiveness. The basic
model, which included needs and other factors expected to have an impact on
quality of life, explained 15.4% of the changes in quality of life, while the
extended model, which included the freedom-of-choice variables, explained 17.4%.
The inclusion of freedom-of-choice variables increased the adjusted coefficient
of determination by 2%. There was a significant positive association between
freedom of choice and the effectiveness of public home care services. CONCLUSION:
Freedom of choice does not exist for all clients of home care who desire it. By
changing social welfare activities and structures, it is possible to show respect
for clients' opinions and to thereby improve the effectiveness of home care
services.
PMID- 27616950
TI - Effect of Named, Accountable GPs on Continuity of Care: Protocol for a Regression
Discontinuity Study of a National Policy Change.
AB - INTRODUCTION: Increasing continuity of care has been identified as a strategy to
improve patient outcomes, but previous studies of integrated care have tended to
focus on pilot areas, which limit their generalisability and the ability to
determine in which contexts integrated care was most successful. OBJECTIVE: This
study protocol describes a quantitative evaluation of a reform in England that
introduced named, accountable general practitioners for all National Health
Service (NHS) patients aged 75 years or over. The national contract for general
practice services required that named general practitioners offer longitudinal
continuity of care within the general practice and be accountable for
coordinating care to meet the patient's healthcare needs. METHODS: This study
will apply a regression discontinuity design to pseudonymised electronic medical
records from a sample of general practices in England. We will compare outcomes
for patients aged just below and above the age of 75 to estimate the effect of
named general practitioners and relate these estimated treatment effects to the
characteristics of general practices. Outcomes will include a metric relating to
continuity of care, namely the Usual Provider of Care Index, and numbers of
general practitioner contacts, referrals to specialist care and diagnostic tests.
DISCUSSION: The study illustrates an approach to evaluate national changes aimed
at more integrated care using electronic records, which will complement in-depth
examination in pilot sites.
PMID- 27616952
TI - Different Models of Hospital-Community Health Centre Collaboration in Selected
Cities in China: A Cross-Sectional Comparative Study.
AB - OBJECTIVE: In recent years, in order to provide patients with seamless and
integrated healthcare services, some models of collaboration between public
hospitals and community health centres have been piloted in some cities in China.
The main goals of this study were to assess the nature and characteristics of
these collaboration models. METHODS: Three cases of three different collaboration
models in three Chinese cities were selected to analyse using descriptive
statistics, Pearson chi (2) and ordinal logistic regression. RESULTS: Results
showed that the Direct Management Model in Wuhan exhibited better structure
indicators than the other two models. Staff in the Direct Management Model had
the highest satisfaction level (77.6%) with respect to patient referral.
Communications between hospitals and community health centres and among care
providers were generally inadequate. Publicity about hospital-community health
centre collaboration was inadequate, resulting in low awareness among patients
and even among health professionals. CONCLUSION: Results can inform health
service delivery integration efforts in China and provide crucial information for
the assessment of similar collaborations in other countries.
PMID- 27616951
TI - Implementing Key Strategies for Successful Network Integration in the Quebec
Substance-Use Disorders Programme.
AB - BACKGROUND: Fragmentation and lack of coordination often occur among
organisations offering treatment for individuals with substance-use disorders.
Better integration from a system perspective within a network of organisations
offering substance-use disorder services can be developed using various
integration strategies at the administrative and clinical levels. This study aims
to identify integration strategies implemented in Quebec substance-use disorder
networks and to assess their strengths and limitations. METHODS: A total of 105
stakeholders representing two regions and four local substance-use disorder
networks participated in focus groups or individual interviews. Thematic
qualitative and descriptive quantitative analyses were conducted. RESULTS: Six
types of service integration strategies have been implemented to varying degrees
in substance-use disorder networks. They are: 1) coordination activities
governance, 2) primary-care consolidation models, 3) information and monitoring
management tools, 4) service coordination strategies, 5) clinical evaluation
tools and 6) training activities. CONCLUSION: Important investments have been
made in Quebec for the training and assessment of individuals with substance-use
disorders, particularly in terms of support for emergency room liaison teams and
the introduction of standardised clinical evaluation tools. However, the
development of integration strategies was insufficient to ensure the
implementation of successful networks. Planning, consolidation of primary care
for substance-use disorders and systematic implementation of various clinical and
administrative integration strategies are needed in order to ensure a better
continuum of care for individuals with substance-use disorders.
PMID- 27616953
TI - Effectiveness of Teamwork in an Integrated Care Setting for Patients with COPD:
Development and Testing of a Self-Evaluation Instrument for Interprofessional
Teams.
AB - INTRODUCTION: Teamwork between healthcare providers is conditional for the
delivery of integrated care. This study aimed to assess the usefulness of the
conceptual framework Integrated Team Effectiveness Model for developing and
testing of the Integrated Team Effectiveness Instrument. THEORY AND METHODS:
Focus groups with healthcare providers in an integrated care setting for people
with chronic obstructive pulmonary disease (COPD) were conducted to examine the
recognisability of the conceptual framework and to explore critical success
factors for collaborative COPD practice out of this framework. The resulting
items were transposed into a pilot instrument. This was reviewed by expert
opinion and completed 153 times by healthcare providers. The underlying structure
and internal consistency of the instrument were verified by factor analysis and
Cronbach's alpha. RESULTS: The conceptual framework turned out to be
comprehensible for discussing teamwork effectiveness. The pilot instrument
measures 25 relevant aspects of teamwork in integrated COPD care. Factor analysis
suggested three reliable components: teamwork effectiveness, team processes and
team psychosocial traits (Cronbach's alpha between 0.76 and 0.81). CONCLUSIONS
AND DISCUSSION: The conceptual framework Integrated Team Effectiveness Model is
relevant in developing a practical full-spectrum instrument to facilitate
discussing teamwork effectiveness. The Integrated Team Effectiveness Instrument
provides a well-founded basis to self-evaluate teamwork effectiveness in
integrated COPD care by healthcare providers. Recommendations are provided for
the improvement of the instrument.
PMID- 27616954
TI - Cross-sector Service Provision in Health and Social Care: An Umbrella Review.
AB - INTRODUCTION: Meeting the complex health needs of people often requires
interaction among numerous different sectors. No one service can adequately
respond to the diverse care needs of consumers. Providers working more
effectively together is frequently touted as the solution. Cross-sector service
provision is defined as independent, yet interconnected sectors working together
to better meet the needs of consumers and improve the quality and effectiveness
of service provision. Cross-sector service provision is expected, yet much
remains unknown about how it is conceptualised or its impact on health status.
This umbrella review aims to clarify the critical attributes that shape cross
sector service provision by presenting the current state of the literature and
building on the findings of the 2004 review by Sloper. METHODS: Literature
related to cross-sector service provision is immense, which poses a challenge for
decision makers wishing to make evidence-informed decisions. An umbrella review
was conducted to articulate the overall state of cross-sector service provision
literature and examine the evidence to allow for the discovery of consistencies
and discrepancies across the published knowledge base. FINDINGS: Sixteen reviews
met the inclusion criteria. Seven themes emerged: Focusing on the consumer,
developing a shared vision of care, leadership involvement, service provision
across the boundaries, adequately resourcing the arrangement, developing novel
arrangements or aligning with existing relationships, and strengthening
connections between sectors. Future research from a cross-organisational, rather
than individual provider, perspective is needed to better understand what shapes
cross-sector service provision at the boundaries. CONCLUSION: Findings aligned
closely with the work done by Sloper and raise red flags related to reinventing
what is already known. Future researchers should look to explore novel areas
rather than looking into areas that have been explored at length. Evaluations of
out-comes related to cross-sector service provision are still needed before any
claims about effectiveness can be made.
PMID- 27616955
TI - Effects of Integrated Care on Disease-Related Hospitalisation and Healthcare
Costs in Patients with Diabetes, Cardiovascular Diseases and Respiratory
Illnesses: A Propensity-Matched Cohort Study in Switzerland.
AB - BACKGROUND: There is an ongoing discussion on the further promotion of integrated
care models in many healthcare systems. Only a few data, which examine the effect
of integrated care models on medical expenditures and quality of care in
chronically ill patients, exist. AIMS: To investigate the effect of integrated
care models on disease-related hospitalisations as a quality indicator and
healthcare costs in patients with either diabetes, cardiovascular diseases or
respiratory illnesses. METHODS: A propensity-matched retrospective cohort study
based on a large Swiss health insurance database (2012-2013) was performed for
three chronic patient groups (diabetes, cardiovascular diseases, respiratory
illnesses), who were enrolled in an integrated care model and compared to
individuals in a standard care model. Multivariate regression models were applied
to estimate the effect of integrated care models on disease-related
hospitalisations and healthcare costs. RESULTS: The matched cohorts included a
total of 12,526 patients with diabetes, 71,778 with cardiovascular diseases and
17,498 with respiratory illnesses, in which each one half was enrolled in
integrated care models and the other half in standard care models. Diabetes and
cardiovascular patients with integrated care models had a significantly lower
probability of disease-related hospitalisation compared to those with standard
care models (p < 0.01). Healthcare costs were statistically significant lower in
all three patient groups with integrated care, but with the highest effect in
patients with diabetes (Swiss francs (CHF) -778). CONCLUSIONS: Integrated care
may provide an effective strategy to improve the quality of care and to reduce
healthcare costs in chronically ill patients. Study findings intend to contribute
to the ongoing political discussion on integrated care and provide evidence for
improved and more effective care of patients with chronic diseases.
PMID- 27616956
TI - Substitution of Hospital Care with Primary Care: Defining the Conditions of
Primary Care Plus.
AB - OBJECTIVE: To analyse barriers and facilitators in substituting hospital care
with primary care to define preconditions for successful implementation. METHODS:
A descriptive feasibility study was performed to collect information on the
feasibility of substituting hospital care with primary care. General
practitioners were able to refer patients, about whom they had doubts regarding
diagnosis, treatment and/or the need to refer to hospital care, to medical
specialists who performed low-complex consultations at general practitioner
practices. Qualitative data were collected through interviews with general
practitioners and medical specialists, focus groups and notes from meetings in
the Netherlands between April 2013 and January 2014. Data were analysed using a
conventional content analysis which resulted in categorised barriers,
facilitators and policy adjustments, after which preconditions were formulated.
RESULTS: The most important preconditions were make arrangements on governmental
level, arrange a collective integrated IT-system, determine the appropriate
profile for medical specialists, design a referral protocol for eligible
patients, arrange deliberation possibilities for general practitioners and
medical specialists and formulate a diagnostic protocol. CONCLUSIONS: The
barriers, facilitators and formulated preconditions provided relevant input to
change the design of substituting hospital care with primary care.
PMID- 27616958
TI - Co-Production at the Strategic Level: Co-Designing an Integrated Care System with
Lay Partners in North West London, England.
AB - In North West London, health and social care leaders decided to design a system
of integrated care with the aim of improving the quality of care and supporting
people to maintain independence and participation in their community. Patients
and carers, known as 'lay partners,' were to be equal partners in co-production
of the system. Lay partners were recruited by sending a role profile to health,
social care and voluntary organisations and requesting nominations. They formed a
Lay Partners Advisory Group from which pairs were allocated to system design
workstreams, such as which population to focus on, financial flow, information
technology and governance. A larger and more diverse Lay Partners Forum provided
feedback on the emerging plans. A key outcome of this approach was the
development of an integration toolkit co-designed with lay partners. Lay partners
provided challenge, encouraged innovation, improved communication, and held the
actions of other partners to account to ensure the vision and aims of the
emerging integrated care system were met. Key lessons from the North West London
experience for effective co-production include: recruiting patients and carers
with experience of strategic work; commitment to the vision; willingness to
challenge and to listen; strong connections within the community being served;
and enough time to do the work. Including lay partners in co-design from the
start, and at every level, was important. Agreeing the principles of working
together, providing support and continuously recruiting lay representatives to
represent their communities are keys to effective co-production.
PMID- 27616957
TI - Profiling Patients' Healthcare Needs to Support Integrated, Person-Centered
Models for Long-Term Disease Management (Profile): Research Design.
AB - BACKGROUND: This article presents the design of PROFILe, a study investigating
which (bio)medical and non-(bio)medical patient characteristics should guide more
tailored chronic care. Based on this insight, the project aims to develop and
validate 'patient profiles' that can be used in practice to determine optimal
treatment strategies for subgroups of chronically ill with similar healthcare
needs and preferences. METHODS/DESIGN: PROFILe is a practice-based research
comprising four phases. The project focuses on patients with type 2 diabetes.
During the first study phase, patient profiles are drafted based on a systematic
literature research, latent class growth modeling, and expert collaboration. In
phase 2, the profiles are validated from a clinical, patient-related and
statistical perspective. Phase 3 involves a discrete choice experiment to gain
insight into the patient preferences that exist per profile. In phase 4, the
results from all analyses are integrated and recommendations formulated on which
patient characteristics should guide tailored chronic care. DISCUSSION: PROFILe
is an innovative study which uses a uniquely holistic approach to assess the
healthcare needs and preferences of chronically ill. The patient profiles
resulting from this project must be tested in practice to investigate the effects
of tailored management on patient experience, population health and costs.
PMID- 27616960
TI - How To Build an Integrated Neighborhood Approach to Support Community-Dwelling
Older People?
AB - BACKGROUND: Although the need for integrated neighborhood approaches (INAs) is
widely recognized, we lack insight into strategies like INA. We describe diverse
Dutch INA partners' experiences to provide integrated person- and population
centered support to community-dwelling older people using an adapted version of
Valentijn and colleagues' integrated care model. Our main objective was to
explore the experiences with INA participation. We sought to increase our
understanding of the challenges facing these partners and identify factors
facilitating and inhibiting integration within and among multiple levels.
METHODS: Twenty-one interviews with INA partners (including local health and
social care organizations, older people, municipal officers, and a health
insurer) were conducted and subjected to latent content analysis. RESULTS: This
study showed that integrated care and support provision through an INA is a
complex, dynamic process requiring multilevel alignment of activities. The INA
achieved integration at the personal, service, and professional levels only
occasionally. Micro-level bottom-up initiatives were not aligned with top-down
incentives, forcing community workers to establish integration despite rather
than because of meso- and macro-level contexts. CONCLUSIONS: Top-down incentives
should be better aligned with bottom-up initiatives. This study further
demonstrated the importance of community-level engagement in integrated care and
support provision.
PMID- 27616962
TI - Aspects of Equality in Mandatory Partnerships - From the Perspective of Municipal
Care in Norway.
AB - INTRODUCTION: This paper raises questions about equality in partnerships, since
imbalance in partnerships may effect collaboration outcomes in integrated care.
We address aspects of equality in mandatory, public-public partnerships, from the
perspective of municipal care. We have developed a questionnaire wherein the
Norwegian Coordination Reform is an illustrative example. The following research
question is addressed: What equality dimensions are important for municipals
related to mandatory partnerships with hospitals? THEORY/METHODS: Since we did
not find any instrument to measure equality in partnerships, an explorative
design was chosen. The development of the instrument was based on the theory on
partnership and knowledge about the field and context. A national online survey
was emitted to all 429 Norwegian municipalities in 2013. The response rate was in
total 58 percent (n = 248). The data were mainly analysed using Principal
component analysis. RESULTS: It seems that the two dimensions "learning and
expertise equality" and "contractual equality" collects reliable and valid data
to measure aspects of equality in partnerships. DISCUSSION: Partnerships are
usually based on voluntarism. The results indicate that mandatory partnerships,
within a public health care system, can be appropriate to equalize partnerships
between health care providers at different care levels.
PMID- 27616961
TI - Outcome Indicators on Interprofessional Collaboration Interventions for Elderly.
AB - BACKGROUND: Geriatric care increasingly needs more multidisciplinary health care
services to deliver the necessary complex and continuous care. The aim of this
study is to summarize indicators of effective interprofessional outcomes for this
population. METHOD: A systematic review is performed in the Cochrane Library,
Pubmed (Medline), Embase, Cinahl and Psychinfo with a search until June 2014.
RESULTS: Overall, 689 references were identified of which 29 studies met the
inclusion criteria. All outcome indicators were summarized in three categories:
collaboration, patient level outcome and costs. Seventeen out of 24 outcome
indicators within the category of 'collaboration' reached significant difference
in advantage of the intervention group. On 'patient outcome level' only 15 out of
32 outcome parameters met statistical significance. In the category of 'costs'
only one study reached statistical significance. DISCUSSION AND CONCLUSION: The
overall effects of interprofessional interventions for elderly are positive, but
based on heterogeneous outcomes. Outcome indicators of interprofessional
collaboration for elderly with a significant effect can be summarized in three
main categories: 'collaboration', patient level' and 'costs'. For 'collaboration'
the outcome indicators are key elements of collaboration, involved disciplines,
professional and patient satisfaction and quality of care. On 'patient level' the
outcome indicators are pain, fall incidence, quality of life, independence for
daily life activities, depression and agitated behaviour, transitions, length of
stay in hospital, mortality and period of rehabilitation. 'Costs' of
interprofessional interventions on short- and long-term for elderly need further
investigation. When organizing interprofessional collaboration or
interprofessional education these outcome indicators can be considered as
important topics to be addressed. Overall more research is needed to gain insight
in the process of interprofessional collaboration and so to learn to work
interprofessionally.
PMID- 27616963
TI - Co-Leadership - A Management Solution for Integrated Health and Social Care.
AB - INTRODUCTION: Co-leadership has been identified as one approach to meet the
managerial challenges of integrated services, but research on the topic is
limited. In the present study, co-leadership, practised by pairs of managers -
each manager representing one of the two principal organizations in integrated
health and social care services - was explored. AIM: To investigate co-leadership
in integrated health and social care, identify essential preconditions in
fulfilling the management assignment, its operationalization and impact on
provision of sustainable integration of health and social care. METHOD:
Interviews with eight managers exercising co-leadership were analysed using
directed content analysis. Respondent validation was conducted through additional
interviews with the same managers. RESULTS: Key contextual preconditions were an
organization-wide model supporting co-leadership and co-location of services.
Perception of the management role as a collective activity, continuous
communication and lack of prestige were essential personal and interpersonal
preconditions. In daily practice, office sharing, being able to give and take and
support each other contributed to provision of sustainable integration of health
and social care. CONCLUSION AND DISCUSSION: Co-leadership promoted robust
management by providing broader competence, continuous learning and joint
responsibility for services. Integrated health and social care services should
consider employing co-leadership as a managerial solution to achieve
sustainability.
PMID- 27616964
TI - Integrated Health Care Barcelona Esquerra (Ais-Be): A Global View of
Organisational Development, Re-Engineering of Processes and Improvement of the
Information Systems. The Role of the Tertiary University Hospital in the
Transformation.
AB - The Integrated Health Area "Barcelona Esquerra" (Area Integral de Salud de
Barcelona Esquerra - AIS-BE), which covers a population of 524,000 residents in
Barcelona city, is running a project to improve healthcare quality and efficiency
based on co-ordination between the different suppliers in its area through the
participation of their professionals. Endowed with an Organisational Model that
seeks decision-taking that starts out from clinical knowledge and from
Information Systems tools that facilitate this co-ordination (an interoperability
platform and a website) it presents important results in its structured
programmes that have been implemented such as the Reorganisation of Emergency
Care, Screening for Colorectal Cancer, the Onset of type 2 Diabetes Mellitus,
Teledermatology and the Development of Cross-sectional Healthcare Policies for
Care in Chronicity.
PMID- 27616965
TI - Early Discharge Planning and Improved Care Transitions: Pre-Admission Assessment
for Readmission Risk in an Elective Orthopedic and Cardiovascular Surgical
Population.
AB - BACKGROUND/METHODS: Readmission prevention is a marker of patient care quality
and requires comprehensive, early discharge planning for safe hospital
transitions. Effectively performed, this process supports patient satisfaction,
efficient resource utilization, and care integration. This study developed/tested
the utility of a predictive early discharge risk assessment with 366 elective
orthopedic/cardiovascular surgery patients. Quality improvement cycles were
undertaken for the design and to inform analytic plan. An 8-item questionnaire,
which includes patient self-reported health, was integrated into care managers'
telephonic pre-admission assessments during a 12-month period. RESULTS:
Regression models found the questionnaire to be predictive of readmission (p <=
.005; R(2) = .334) and length-of-stay (p <= .001; R(2) = .314). Independent
variables of "lives-alone" and "self-rated health" were statistically significant
for increased readmission odds, as was "self-rated health" for increased length
of-stay. Quality measures, patient experience and increased rates of discharges
to-home further supported the benefit of embedding these questions into the pro
active planning process. CONCLUSION: The pilot discharge risk assessment was
predictive of readmission risk and length-of-stay for elective
orthopedic/cardiovascular patients. Given the usability of the questionnaire in
advance of elective admissions, it can facilitate pro-active discharge planning
essential for producing quality outcomes and addressing new reimbursement
methodologies for continuum-based episodes of care.
PMID- 27616966
TI - Interorganizational Collaboration in Transitional Care - A Study of a Post
Discharge Programme for Elderly Patients.
AB - INTRODUCTION AND AIM: This article reports a study of a post-discharge programme
for elderly patients in Norway. It took place in an intermediate ward for
transitional care and was based on collaboration between a municipality and a
hospital, which was part of a health enterprise. The aim of the study was to
analyse the collaboration and its possible effects on the quality of patient
care, and the economic efficiency of the project for the organizations involved.
METHODOLOGY: A mixed-methods approach, consisting of interviews, questionnaires
and analyses of official documents and statistics. RESULTS: The collaboration was
working well on the top level of the organizations, but was more problematic on
the operative level. However, there were clear signs of improvement. The patients
who received transitional care were more satisfied with their stay at the ward
than their previous stay at the hospital. They were discharged to their homes
more often and perceived to have a higher level of functioning than the hospital
patients. Average costs per patient were also lower in the ward than in the
hospital departments. CONCLUSION: The collaboration had mainly positive impacts
on the quality of patient care and the economic efficiency of elderly care in the
municipality. However, the board of the health enterprise decided to close down
the intermediate ward.
PMID- 27616967
TI - The Role of Care Coordinator for Children with Complex Care Needs: A Systematic
Review.
AB - INTRODUCTION: This systematic review seeks to identify the intended components of
the role of care coordinator for children with complex care needs and the factors
that determine its composition in practice. THEORY AND METHODS: The initial
search identified 1,157 articles, of which 37 met the inclusion criteria. They
were quality assessed using the SIGN hierarchy of evidence structure. RESULTS:
Core components of the role include: coordination of care needs, planning and
assessment, specialist support, emotional support, administration and logistics
and continuing professional development. Influencing factors on the role include
the external environment (political and socio-economic), the internal environment
(organisational structure and funding protocols), the skills, qualifications and
experience of the coordinator, the family circumstances and the nature of the
interaction between the care coordinator and the family. DISCUSSION: The lack of
consistent terminology creates challenges and there is a need for greater
consensus on this issue. Organisations and healthcare professionals need to
recognise the extent to which contextual factors influence the role of a care
coordinator in practice and plan accordingly. Despite evidence that suggests that
the role is pivotal in ensuring that care needs are sustained, there remains
great variability in the understanding of the role of a care coordinator for this
population. CONCLUSIONS: As the provision of care increasingly moves closer to
home there is a need for greater understanding of the nature and composition of
the interaction between care coordinators and families to determine the extent to
which appropriate services are being provided. Further work in this area should
take into consideration any potential variance in service provision, for example
any potential inequity arising due to geographic location. It is also imperative,
where appropriate, to seek the views of children with complex care needs and
their siblings about their experiences.
PMID- 27616969
TI - Evaluation of an Organisational Intervention to Promote Integrated Working
between Health Services and Care Homes in the Delivery of End-of-Life Care for
People with Dementia: Understanding the Change Process Using a Social Identity
Approach.
AB - In the United Kingdom, approximately a third of people with dementia live in long
term care facilities for adults, the majority of whom are in the last years of
life. Working arrangements between health services and care homes in England are
largely ad hoc and often inequitable, yet quality end-of-life care for people
with dementia in these settings requires a partnership approach to care that
builds on existing practice. This paper reports on the qualitative component of a
mixed method study aimed at evaluating an organisational intervention shaped by
Appreciative Inquiry to promote integrated working between visiting health care
practitioners (i.e. General Practitioners and District Nurses) and care home
staff. The evaluation uses a social identity approach to elucidate the mechanisms
of action that underlie the intervention, and understand how organisational
change can be achieved. We uncovered evidence of both (i) identity mobilisation
and (ii) context change, defined in theory as mechanisms to overcome divisions in
healthcare. Specifically, the intervention supported integrated working across
health and social care settings by (i) the development of a common group identity
built on shared views and goals, but also recognition of knowledge and expertise
specific to each service group which served common goals in the delivery of end
of-life care, and (ii) development of context specific practice innovations and
the introduction of existing end-of-life care tools and frameworks, which could
consequently be implemented as part of a meaningful bottom-up rather than top
down process. Interventions structured around a Social Identity Approach can be
used to gauge the congruence of values and goals between service groups without
which efforts to achieve greater integration between different health services
may prove ineffectual. The strength of the approach is its ability to accommodate
the diversity of service groups involved in a given area of care, by valuing
their respective contributions and building on existing ways of working within
which practice changes can be meaningfully integrated.
PMID- 27616970
TI - Towards People-Centred Integrated Care: From Passive Recognition to Active Co
production?
PMID- 27616968
TI - Assessment of Patients' Perception of Telemedicine Services Using the Service
User Technology Acceptability Questionnaire.
AB - INTRODUCTION: The purpose of this paper is to assess if similar telemedicine
services integrated in the management of different chronic diseases are
acceptable and well perceived by patients or if there are any negative
perceptions. THEORY AND METHODS: Participants suffering from different chronic
diseases were enrolled in Veneto Region and gathered into clusters. Each cluster
received a similar telemedicine service equipped with different disease-specific
measuring devices. Participants were patients with diabetes (n = 163), chronic
obstructive pulmonary disease (n = 180), congestive heart failure (n = 140) and
Cardiac Implantable Electronic Devices (n = 1635). The Service User Technology
Acceptability Questionnaire (SUTAQ) was initially translated, culturally adapted
and pretested and subsequently used to assess patients' perception of
telemedicine. Data were collected after 3 months and after 12 months from the
beginning of the intervention. Data for patients with implantable devices was
collected only at 12 months. RESULTS: Results at 12 months for all clusters are
similar and assessed a positive perception of telemedicine. The SUTAQ results for
clusters 2 (diabetes), 5 (COPD) and 7 (CHF) after 3 months of intervention were
confirmed after 12 months. CONCLUSIONS: Telemedicine was perceived as a viable
addition to usual care. A positive perception for telemedicine services isn't a
transitory effect, but extends over the course of time.
PMID- 27616972
TI - Communities advancing the studies of Tribal nations across their lifespan:
Design, methods, and baseline of the CoASTAL cohort.
AB - The CoASTAL cohort represents the first community cohort assembled to study a HAB
related illness. It is comprised of three Native American tribes in the Pacific
NW for the purpose of studying the health impacts of chronic, low level domoic
acid (DA) exposure through razor clam consumption. This cohort is at risk of
domoic acid (DA) toxicity by virtue of their geographic location (access to
beaches with a history of elevated DA levels in razor clams) and the cultural and
traditional significance of razor clams in their diet. In this prospective,
longitudinal study, Wave 1 of the cohort is comprised of 678 members across the
lifespan with both sexes represented within child, adult and geriatric age
groups. All participants are followed annually with standard measures of medical
and social history; neuropsychological functions, psychological status, and
dietary exposure. DA concentration levels are measured at both public and
reservation beaches where razor clams are sourced and multiple metrics have been
piloted to further determine exposure. Baseline data indicates that all cognitive
and psychological functions are within normal limits. In addition there is
considerable variability in razor clam exposure. Therefore, the CoASTAL cohort
offers a unique opportunity to investigate the potential health effects of
chronic, low level exposure to DA over time.
PMID- 27616973
TI - Assessment of sodium channel mutations in Makah Tribal members of the U.S.
Pacific Northwest as a potential mechanism of resistance to paralytic shellfish
poisoning.
AB - The Makah Tribe of Neah Bay, Washington, has historically relied on the
subsistence harvest of coastal seafood, including shellfish, which remains an
important cultural and ceremonial resource. Tribal legend describes visitors from
other tribes that died from eating shellfish collected on Makah lands. These
deaths were believed to be caused by paralytic shellfish poisoning, a human
illness caused by ingestion of shellfish contaminated with saxitoxins, which are
produced by toxin-producing marine dinoflagellates on which the shellfish feed.
These paralytic shellfish toxins include saxitoxin, a potent Na+ channel
antagonist that binds to the pore region of voltage gated Na+ channels. Amino
acid mutations in the Na+ channel pore have been demonstrated to confer
resistance to saxitoxin in softshell clam populations exposed to paralytic
shellfish toxins present in their environment. Because of the notion of
resistance to paralytic shellfish toxins, we aimed to determine if a resistance
strategy was possible in humans with historical exposure to toxins in shellfish.
We collected, extracted and purified DNA from buccal swabs of 83 volunteer Makah
tribal members and sequenced the skeletal muscle Na+ channel (Nav1.4) at nine
loci to characterize potential mutations in the relevant saxitoxin binding
regions. No mutations of these specific regions were identified after comparison
to a reference sequence. This study suggests that any resistance of Makah Tribal
members to saxitoxin is not a function of Nav1.4 modification but may be due to
mutations in neuronal or cardiac sodium channels or some other mechanism
unrelated to sodium channel function.
PMID- 27616971
TI - Harmful Algal Blooms and Public Health.
AB - The five most commonly recognized Harmful Algal Bloom related illnesses include
Ciguatera poisoning, Paralytic Shellfish poisoning, Neurotoxin Shellfish
poisoning, Diarrheic Shellfish Poisoning and Amnesic Shellfish poisoning.
Although they are each the product of different toxins, toxin assemblages or HAB
precursors these clinical syndromes have much in common. Exposure occurs through
the consumption of fish or shellfish; routine clinical tests are not available
for diagnosis; there is no known antidote for exposure; and the risk of these
illnesses can negatively impact local fishing and tourism industries. Thus,
illness prevention is of paramount importance to minimize human and public health
risks. To accomplish this, close communication and collaboration is needed among
HAB scientists, public health researchers and local, state and tribal health
departments at academic, community outreach, and policy levels.
PMID- 27616974
TI - Perception of risk for Domoic Acid related health problems: A Cross-cultural
study.
AB - Risk perception is a complex process that refers to the way people approach,
think about and interpret risks in their environment. An important element of
risk perception is that it is culturally situated. Since HAB's can present a
health risk in many places around the world, looking at cultural parameters for
understanding and interpreting risks are important. This study examined how two
different groups of people perceive the potential health risks of low level
exposure to domoic acid (DA) through razor clam consumption. The risk perceptions
of Washington State, USA coastal dwelling Native American nations (NA) were
compared to that of a community sample of recreational razor clam harvesters
(CRH). Overall, the findings support the hypothesis that cultural and community
specific contexts impact the perception of risk of a DA related illness.
Specifically, the NA sample was distinguished by worrying more about ocean
pollution, attributing DA risks to climate change, expressing concerns about the
potential impact of DA on future generations, and feeling better informed than
the CRH group. The CRH group were more likely to attribute the DA problem to
anthropogenic or industrial causes; and view the risk of health problems as lower
than that associated with smoking, high cholesterol, anxiety or depression,
alcoholism, high blood pressure or obesity. The CRH group was also more likely to
turn to the media for DA related information. Both groups trust the decisions of
state and tribe health and natural resources officials and demonstrated a complex
pattern of findings that involved gender. It was recommended that risk
communication and outreach activities are designed to take into consideration
factors that specifically apply to each cultural community.
PMID- 27616975
TI - Dietary Assessment of domoic acid Exposure: What can be learned from traditional
methods and new applications for a technology assisted device.
AB - Three Tribal Nations in the Pacific Northwest United States comprise the members
of the CoASTAL cohort. These populations may be at risk for neurobehavioral
impairment, i.e., amnesic shellfish poisoning, from shellfish consumption as a
result of repeated, low-level domoic acid (DA) exposure present in local clams.
Previous work with this cohort confirmed a high proportion of clam consumers with
varying levels of potential exposure over time. Since clams are an episodically
consumed food, traditional dietary records do not fully capture exposure.
Frequency questionnaires can capture accumulated doses over time and this data
can be used to examine dose-response relationships with periodic studies of
memory and learning. However, frequency questionnaires cannot be used to assess
consumption and memory response in real time. To address this shortcoming, a
modified technology assisted dietary assessment (TADA) iPod application was
developed to capture images of the clam meal, sourcing data, and associated
memory functioning within 24 hours and seven days after consumption. This
methodology was piloted with razor clam meals consumed by members from the
CoASTAL cohort. Preliminary findings suggest that the TADA iPod application is
potentially useful in collecting real-time data with respect to razor clam
consumption, as well as one day and seven day memory outcome data. This
technology holds promise for addressing the challenges of other HAB related
dietary exposure outcome studies.
PMID- 27616976
TI - Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics
and lipidomics.
AB - INTRODUCTION: Cellular metabolism is altered during cancer initiation and
progression, which allows cancer cells to increase anabolic synthesis, avoid
apoptosis and adapt to low nutrient and oxygen availability. The metabolic nature
of cancer enables patient cancer status to be monitored by metabolomics and
lipidomics. Additionally, monitoring metabolic status of patients or biological
models can be used to greater understand the action of anticancer therapeutics.
OBJECTIVES: Discuss how metabolomics and lipidomics can be used to (i) identify
metabolic biomarkers of cancer and (ii) understand the mechanism-of-action of
anticancer therapies. Discuss considerations that can maximize the clinical value
of metabolic cancer biomarkers including case-control, prognostic and
longitudinal study designs. METHODS: A literature search of the current relevant
primary research was performed. RESULTS: Metabolomics and lipidomics can identify
metabolic signatures that associate with cancer diagnosis, prognosis and disease
progression. Discriminatory metabolites were most commonly linked to lipid or
energy metabolism. Case-control studies outnumbered prognostic and longitudinal
approaches. Prognostic studies were able to correlate metabolic features with
future cancer risk, whereas longitudinal studies were most effective for studying
cancer progression. Metabolomics and lipidomics can help to understand the
mechanism-of-action of anticancer therapeutics and mechanisms of drug resistance.
CONCLUSION: Metabolomics and lipidomics can be used to identify biomarkers
associated with cancer and to better understand anticancer therapies.
PMID- 27616977
TI - Attracting, equipping and retaining young medical doctors in HIV vaccine science
in South Africa.
AB - BACKGROUND: HIV remains a significant health problem in South Africa (SA). The
development of a preventive vaccine offers promise as a means of addressing the
epidemic, yet development of the human resource capacity to facilitate such
research in SA is not being sustained. The HIV Vaccine Trials Network (HVTN) has
responded by establishing South African/HVTN AIDS Early Stage Investigator
Programme (SHAPe), a programme to identify, train and retain clinician scientists
in HIV vaccine research in SA. OBJECTIVES: The present study sought to identify
factors influencing the attraction and retention of South African medical doctors
in HIV vaccine research; to understand the support needed to ensure their
success; and to inform further development of clinician research programmes,
including SHAPe. METHODS: Individual interviews and focus groups were held and
audio-recorded with 18 senior and junior research investigators, and medical
doctors not involved in research. Recordings were transcribed, and data were
coded and analysed. RESULTS: Findings highlighted the need for: (1) medical
training programmes to include a greater focus on fostering interest and
developing research skills, (2) a more clearly defined career pathway for
individuals interested in clinical research, (3) an increase in programmes that
coordinate and fund research, training and mentorship opportunities and (4)
access to academic resources such as courses and libraries. Unstable funding
sources and inadequate local funding support were identified as barriers to
promoting HIV research careers. CONCLUSION: Expanding programmes that provide
young investigators with funded research opportunities, mentoring, targeted
training and professional development may help to build and sustain SA's next
generation of HIV vaccine and prevention scientists.
PMID- 27616978
TI - Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild
Traumatic Brain Injury.
AB - Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic
brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in
rats. Here, we examined whether the experience of head trauma affects stress
reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned
to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were
measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess
neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34),
PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the
neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone
(ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum.
For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post
stressor for determination of corticosterone (CORT) levels after stress or
context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI
rats without remission for 28 days after injury. No differences were observed
between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In
serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced
ANDRO elevations were greater than those in mTBI rats. As a positive allosteric
modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO
levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the
aftermath of mTBI on coping warrants further elaboration.
PMID- 27616979
TI - Circular RNAs: Novel Regulators of Neuronal Development.
AB - Circular RNAs (circRNAs) are highly stable, circularized long non-coding RNAs.
circRNAs are conserved across species and appear to be specifically enriched in
the nervous system. Recent studies show that many circRNAs are expressed in a
tissue- and developmental-stage-specific manner, reveal a striking regulation of
circRNAs during neuronal development, and detect their presence at synaptic
sites. The exact functions of circRNAs remain poorly understood, but evidence
from analysis of some circRNA molecules suggests that they could substantially
contribute to the regulation of gene expression, particularly in architecturally
complex and polarized cells such as neurons. Emerging evidence also indicates
that circRNAs are involved in the development and progression of various
neurological disorders. In this review, we summarize the molecular
characteristics of circRNAs and discuss their proposed functions and mechanism-of
action in developing neurons.
PMID- 27616980
TI - Transient Receptor Potential Vanilloid 4 Inhibits gamma-Aminobutyric Acid
Activated Current in Hippocampal Pyramidal Neurons.
AB - The balance between excitatory and inhibitory neurotransmitter systems is crucial
for the modulation of neuronal excitability in the central nervous system (CNS).
The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to
enhance the response of hippocampal glutamate receptors, but whether the
inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown.
gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
CNS. Here, we show that application of transient receptor potential vanilloid 4
(TRPV4) synthetic (GSK1016790A or 4alpha-PDD) or endogenous agonist (5,6-EET)
inhibited GABA-activated current (I GABA) in hippocampal CA1 pyramidal neurons,
which was blocked by specific antagonists of TRPV4 and of GABAA receptors.
GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK)
and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which
was attenuated by removing extracellular calcium or by a calcium/calmodulin
dependent protein kinase kinase-beta antagonist. GSK1016790A-induced decrease of
p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited I
GABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K)
agonist. GSK1016790A-induced inhibition of I GABA was also significantly
attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein
kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We
conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated
by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and
activation of PKC signaling. Inhibition of GABAA receptors may account for the
neuronal hyperexcitability caused by TRPV4 activation.
PMID- 27616981
TI - Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the
Postnatal Murine Retina.
AB - The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4)
are crucial for retinal development and function, and increasing evidence points
at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise
regulation of retinal TH supply is required for proper retinal function, but
knowledge on these mechanisms is still fragmentary. Several transmembrane
transporters have been described as key regulators of TH availability in target
tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity
transporter for T4 and T3, plays an essential role in the central nervous system.
Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the
postnatal availability of MCT8 in the mammalian retina was not reported to date.
In the present study, spatiotemporal retinal MCT8 availability was examined in
mice of different age. For this purpose, we quantified expression levels of Mct8
via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile
and adult age groups. Additionally, age-dependent MCT8 protein levels were
quantified via Western blotting and localized via immunofluorescence confocal
microscopy. While no difference in Mct8 expression levels could be detected
between age groups, MCT8 protein levels in juvenile animals were about two times
higher than in adult animals based on Western blot analyses. Immunohistochemical
analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the
retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly
observed along the apical membrane of the retinal pigment epithelium, tightly
surrounding photoreceptor outer segments. Distinct immunopositive staining was
also detected in the inner nuclear layer and the ganglion cell layer. However, in
adult specimens, immunoreactivity visibly declined in all layers, which was in
line with Western blot analyses. Since MCT8 was abundantly present in juvenile
and about twofold lower in adult retinae, our findings suggest a pivotal role of
MCT8 especially during postnatal maturation. The present study provides novel
insights into age-dependent retinal TH supply, which might help to understand
different aspects regarding retinal development, function, and disorders.
PMID- 27616983
TI - A Pragmatic Oscillome: Aligning Visual Attentional Mechanisms with Language
Comprehension.
PMID- 27616982
TI - Ontogenic Changes and Differential Localization of T-type Ca(2+) Channel Subunits
Cav3.1 and Cav3.2 in Mouse Hippocampus and Cerebellum.
AB - T-type calcium (Ca(2+)) channels play a central role in regulating membrane
excitability in the brain. Although the contributions of T-type current to neuron
output is often proposed to reflect a differential distribution of T-type channel
subtypes to somato-dendritic compartments, their precise subcellular
distributions in central neurons are not fully determined. Using histoblot and
high-resolution immunoelectron microscopic techniques, we have investigated the
expression, regional distribution and subcellular localization of T-type Cav3.1
and Cav3.2 channel subunits in the adult brain, as well as the ontogeny of
expression during postnatal development. Histoblot analysis showed that Cav3.1
and Cav3.2 proteins were widely expressed in the brain, with mostly non
overlapping patterns. Cav3.1 showed the highest expression level in the molecular
layer (ml) of the cerebellum (Cb), and Cav3.2 in the hippocampus (Hp) and the ml
of Cb. During development, levels of Cav3.1 and Cav3.2 increased with age,
although there were marked region- and developmental stage-specific differences
in their expression. At the cellular and subcellular level, immunoelectron
microscopy showed that labeling for Cav3.1 was present in somato-dendritic
domains of hippocampal interneurons and Purkinje cells (PCs), while Cav3.2 was
present in somato-dendritic domains of CA1 pyramidal cells, hippocampal
interneurons and PCs. Most of the immunoparticles for Cav3.1 and Cav3.2 were
either associated with the plasma membrane or the intracellular membranes, with
notable differences depending on the compartment. Thus, Cav3.1 was mainly located
in the plasma membrane of interneurons, whereas Cav3.2 was mainly located in the
plasma membrane of dendritic spines and had a major intracellular distribution in
dendritic shafts. In PCs, Cav3.1 and Cav3.2 showed similar distribution patterns.
In addition to its main postsynaptic distribution, Cav3.2 but not Cav3.1 was also
detected in axon terminals establishing excitatory synapses. These results shed
new light on the subcellular localization of T-type channel subunits and provide
evidence for the non-uniform distribution of Cav3.1 and Cav3.2 subunits over the
plasma membrane of central neurons, which may account for the functional
heterogeneity of T-type mediated current.
PMID- 27616984
TI - Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine
Inactivation.
AB - Glutamate stimulates ventral midbrain (VM) N-Methyl-D-Aspartate receptors (NMDAR)
to initiate dopamine (DA) burst firing activity, a mode of discharge associated
with enhanced DA release and reward. Blockade of VM NMDAR, however, enhances
brain stimulation reward (BSR), the results can be explained by a reduction in
the inhibitory drive on DA neurons that is also under the control of glutamate.
In this study, we used fast-scan cyclic voltammetry (FSCV) in anesthetized
animals to determine whether this enhancement is associated with a change in
phasic DA release in the nucleus accumbens. Rats were implanted with a
stimulation electrode in the dorsal-raphe (DR) and bilateral cannulae above the
VM and trained to self-administer trains of electrical stimulation. The curve
shift method was used to evaluate the effect of a single dose (0.825 nmol/0.5
MUl/side) of the NMDAR antagonist, (2R,4S)-4-(3-Phosphopropyl)-2
piperidinecarboxylic acid (PPPA), on reward. These animals were then anesthetized
and DA release was measured during delivery of electrical stimulation before and
after VM microinjection of the vehicle followed by PPPA. As expected, phasic DA
release and operant responding depended similarly on the frequency of rewarding
electrical stimulation. As anticipated, PPPA produced a significant reward
enhancement. Unexpectedly, PPPA produced a decrease in the magnitude of DA
transients at all tested frequencies. To test whether this decrease resulted from
excessive activation of DA neurons, we injected apomorphine 20 min after PPPA
microinjection. At a dose (100 MUg s.c.) sufficient to reduce DA firing under
control conditions, apomorphine restored electrical stimulation-induced DA
transients. These findings show that combined electrical stimulation and VM
NMDARs blockade induce DA inactivation, an effect that indirectly demonstrates
that VM NMDARs blockade enhances reward by potentiating stimulation-induced
excitation in the mesoaccumbens DA pathway.
PMID- 27616985
TI - Activation of NO-cGMP Signaling Rescues Age-Related Memory Impairment in
Crickets.
AB - Age-related memory impairment (AMI) is a common feature and a debilitating
phenotype of brain aging in many animals. However, the molecular mechanisms
underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a
useful experimental animal for studying age-related changes in learning and
memory capability; because the cricket has relatively short life-cycle and a high
capability of olfactory learning and memory. Moreover, the molecular mechanisms
underlying memory formation in crickets have been examined in detail. In the
present study, we trained male crickets of different ages by multiple-trial
olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3
weeks after the final molt (3-week-old crickets) exhibited levels of retention
similar to those of 1-week-old crickets at 30 min or 2 h after training; however
they showed significantly decreased levels of 1-day retention, indicating AMI in
long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory
learning of crickets. Furthermore, 3-week-old crickets injected with a nitric
oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into
the hemolymph before conditioning exhibited a normal level of LTM, the same level
as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog
injection was absent when the crickets were injected after the conditioning. For
the first time, an NO donor and a cGMP analog were found to antagonize the age
related impairment of LTM formation, suggesting that deterioration of NO synthase
(NOS) or molecules upstream of NOS activation is involved in brain-aging
processes.
PMID- 27616986
TI - Feasibility of BCI Control in a Realistic Smart Home Environment.
AB - Smart homes have been an active area of research, however despite considerable
investment, they are not yet a reality for end-users. Moreover, there are still
accessibility challenges for the elderly or the disabled, two of the main
potential targets for home automation. In this exploratory study we design a
control mechanism for smart homes based on Brain Computer Interfaces (BCI) and
apply it in the "Domus" smart home platform in order to evaluate the potential
interest of users about BCIs at home. We enable users to control lighting, a TV
set, a coffee machine and the shutters of the smart home. We evaluate the
performance (accuracy, interaction time), usability and feasibility (USE
questionnaire) on 12 healthy subjects and 2 disabled subjects. We find that
healthy subjects achieve 77% task accuracy. However, disabled subjects achieved a
better accuracy (81% compared to 77%).
PMID- 27616987
TI - Virtual Avatar for Emotion Recognition in Patients with Schizophrenia: A Pilot
Study.
AB - Persons who suffer from schizophrenia have difficulties in recognizing emotions
in others' facial expressions, which affects their capabilities for social
interaction and hinders their social integration. Photographic images have
traditionally been used to explore emotion recognition impairments in
schizophrenia patients, but they lack of the dynamism that is inherent to facial
expressiveness. In order to overcome those inconveniences, over the last years
different authors have proposed the use of virtual avatars. In this work, we
present the results of a pilot study that explored the possibilities of using a
realistic-looking avatar for the assessment of emotion recognition deficits in
patients who suffer from schizophrenia. In the study, 20 subjects with
schizophrenia of long evolution and 20 control subjects were invited to recognize
a set of facial expressions of emotions showed by both the said virtual avatar
and static images. Our results show that schizophrenic patients exhibit
recognition deficits in emotion recognition from facial expressions regardless
the type of stimuli (avatar or images), and that those deficits are related with
the psychopathology. Finally, some improvements in recognition rates (RRs) for
the patient group when using the avatar were observed for sadness or surprise
expressions, and they even outperform the control group in the recognition of the
happiness expression. This leads to conclude that, apart from the dynamism of the
shown expression, the RRs for schizophrenia patients when employing animated
avatars may depend on other factors which need to be further explored.
PMID- 27616988
TI - Attention Diversion Improves Response Inhibition of Immediate Reward, But Only
When it Is Beneficial: An fMRI Study.
AB - Deficits of self-control are associated with a number of mental state disorders.
The ability to direct attention away from an alluring stimulus appears to aid
inhibition of an impulsive response. However, further functional imaging research
is required to assess the impact of shifts in attention on self-regulating
processes. We varied the level of attentional disengagement in an functional
magnetic resonance imaging (fMRI)-based Go/No-go task to probe whether diversion
of attention away from alluring stimuli facilitates response inhibition. We used
the attention-grabbing characteristic of faces to exogenously direct attention
away from stimuli and investigated the relative importance of attention and
response inhibition mechanisms under different delayed reward scenarios [i.e.,
where forgoing an immediate reward ($1) led to a higher ($10) or no payoff in the
future]. We found that diverting attention improved response inhibition
performance, but only when resistance to an alluring stimulus led to delayed
reward. Region of interest analyses indicated significant increased activity in
posterior right inferior frontal gyrus during successful No-go trials for delayed
reward trials compared to no delayed reward trials, and significant reduction in
activity in the superior temporal gyri and left caudate in contexts of high
attentional diversion. Our findings imply that strategies that increase the
perceived benefits of response inhibition might assist individuals in abstaining
from problematic impulsive behaviors.
PMID- 27616989
TI - Multifactorial Modeling of Impairment of Evoked Gamma Range Oscillations in
Schizophrenia.
AB - Despite a significant increase in efforts to identify biomarkers and
endophenotypic measures of psychiatric illnesses, only a very limited amount of
computational models of these markers and measures has been implemented so far.
Moreover, existing computational models dealing with biomarkers typically only
examine one possible mechanism in isolation, disregarding the possibility that
other combinations of model parameters might produce the same network behavior
(what has been termed "multifactoriality"). In this study we describe a step
toward a computational instantiation of an endophenotypic finding for
schizophrenia, namely the impairment of evoked auditory gamma and beta
oscillations in schizophrenia. We explore the multifactorial nature of this
impairment using an established model of primary auditory cortex, by performing
an extensive search of the parameter space. We find that single network
parameters contain only little information about whether the network will show
impaired gamma entrainment and that different regions in the parameter space
yield similar network level oscillation abnormalities. These regions in the
parameter space, however, show strong differences in the underlying network
dynamics. To sum up, we present a first step toward an in silico instantiation of
an important biomarker of schizophrenia, which has great potential for the
identification and study of disease mechanisms and for understanding of existing
treatments and development of novel ones.
PMID- 27616991
TI - Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging:
The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive
Performances.
AB - Normal aging is related to a decline in specific cognitive processes, in
particular in executive functions and memory. In recent years a growing number of
studies have focused on changes in brain functional connectivity related to
cognitive aging. A common finding is the decreased connectivity within multiple
resting state networks, including the default mode network (DMN) and the salience
network. In this study, we measured resting state activity using fMRI and
explored whether cognitive decline is related to altered functional connectivity.
To this end we used a machine learning approach to classify young and old
participants from functional connectivity data. The originality of the approach
consists in the prediction of the performance and age of the subjects based on
functional connectivity by using a machine learning approach. Our findings showed
that the connectivity profile between specific networks predicts both the age of
the subjects and their cognitive abilities. In particular, we report that the
connectivity profiles between the salience and visual networks, and the salience
and the anterior part of the DMN, were the features that best predicted the age.
Moreover, independently of the age of the subject, connectivity between the
salience network and various specific networks (i.e., visual, frontal) predicted
episodic memory skills either based on a standard assessment or on an
autobiographical memory task, and short-term memory binding. Finally, the
connectivity between the salience and the frontal networks predicted inhibition
and updating performance, but this link was no longer significant after removing
the effect of age. Our findings confirm the crucial role of episodic memory and
executive functions in cognitive aging and suggest a pivotal role of the salience
network in neural reorganization in aging.
PMID- 27616992
TI - A Comparative Analysis of 2D and 3D Tasks for Virtual Reality Therapies Based on
Robotic-Assisted Neurorehabilitation for Post-stroke Patients.
AB - Post-stroke neurorehabilitation based on virtual therapies are performed
completing repetitive exercises shown in visual electronic devices, whose content
represents imaginary or daily life tasks. Currently, there are two ways of
visualization of these task. 3D virtual environments are used to get a three
dimensional space that represents the real world with a high level of detail,
whose realism is determinated by the resolucion and fidelity of the objects of
the task. Furthermore, 2D virtual environments are used to represent the tasks
with a low degree of realism using techniques of bidimensional graphics. However,
the type of visualization can influence the quality of perception of the task,
affecting the patient's sensorimotor performance. The purpose of this paper was
to evaluate if there were differences in patterns of kinematic movements when
post-stroke patients performed a reach task viewing a virtual therapeutic game
with two different type of visualization of virtual environment: 2D and 3D. Nine
post-stroke patients have participated in the study receiving a virtual therapy
assisted by PUPArm rehabilitation robot. Horizontal movements of the upper limb
were performed to complete the aim of the tasks, which consist in reaching
peripheral or perspective targets depending on the virtual environment shown.
Various parameter types such as the maximum speed, reaction time, path length, or
initial movement are analyzed from the data acquired objectively by the robotic
device to evaluate the influence of the task visualization. At the end of the
study, a usability survey was provided to each patient to analysis his/her
satisfaction level. For all patients, the movement trajectories were enhanced
when they completed the therapy. This fact suggests that patient's motor recovery
was increased. Despite of the similarity in majority of the kinematic parameters,
differences in reaction time and path length were higher using the 3D task.
Regarding the success rates were very similar. In conclusion, the using of 2D
environments in virtual therapy may be a more appropriate and comfortable way to
perform tasks for upper limb rehabilitation of post-stroke patients, in terms of
accuracy in order to effectuate optimal kinematic trajectories.
PMID- 27616993
TI - Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of
Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients.
AB - Natural killer cells are an integral part of the immune system and represent a
large proportion of the lymphocyte population in the liver. The activity of these
cells is regulated by various cell surface receptors, such as killer Ig-like
receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the
target cell. The composition of KIR receptors has been suggested to influence the
development of specific diseases, in particularly autoimmune diseases, cancer and
reproductive diseases. The role played in idiosyncratic drug-induced liver injury
(DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA
class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for
potential risk associations. One hundred and two AC DILI patients and 226
controls were genotyped for the presence or absence of 16 KIR loci, including the
two pseudogenes 2DP1 and 3DP1. No significant differences were found in the
distribution of individual KIRs between patients and controls, which were
comparable to previously reported KIR data from ethnically similar cohorts. The
21.6 and 21.2% of the patients and controls, respectively, were homozygous
haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one
B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls)
different gene profiles, with 19 being present in both groups. The most frequent
Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2,
3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the
controls. The distribution of HLA class I epitopes did not differ significantly
between AC DILI patients and controls. The most frequent receptor-ligand
combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4
motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%)
predominated in the controls. This is to our knowledge the first analysis of KIR
receptor-HLA ligand associations in DILI, although our findings do not support
evidence of these genetic variations playing a major role in AC DILI development.
PMID- 27616994
TI - Reduced Sodium Current in the Lateral Ventricular Wall Induces Inferolateral J
Waves.
AB - BACKGROUND: J-waves in inferolateral leads are associated with a higher risk for
idiopathic ventricular fibrillation. We aimed to test potential mechanisms
(depolarization or repolarization dependent) responsible for inferolateral J
waves. We hypothesized that inferolateral J-waves can be caused by regional
delayed activation of myocardium that is activated late during normal conditions.
METHODS: Computer simulations were performed to evaluate how J-point elevation is
influenced by reducing sodium current conductivity (GNa), increasing transient
outward current conductivity (Gto), or cellular uncoupling in three predefined
ventricular regions (lateral, anterior, or septal). Two pig hearts were
Langendorff-perfused with selective perfusion with a sodium channel blocker of
lateral or anterior/septal regions. Volume-conducted pseudo-electrocardiograms
(ECG) were recorded to detect the presence of J-waves. Epicardial unipolar
electrograms were simultaneously recorded to obtain activation times (AT).
RESULTS: Simulation data showed that conduction slowing, caused by reduced sodium
current, in lateral, but not in other regions induced inferolateral J-waves. An
increase in transient outward potassium current or cellular uncoupling in the
lateral zone elicited slight J-point elevations which did not meet J-wave
criteria. Additional conduction slowing in the entire heart attenuated J-waves
and J-point elevations on the ECG, because of masking by the QRS. Experimental
data confirmed that conduction slowing attributed to sodium channel blockade in
the left lateral but not in the anterior/septal ventricular region induced
inferolateral J-waves. J-waves coincided with the delayed activation. CONCLUSION:
Reduced sodium current in the left lateral ventricular myocardium can cause
inferolateral J-waves on the ECG.
PMID- 27616995
TI - Evolution of Centrality Measurements for the Detection of Essential Proteins in
Biological Networks.
PMID- 27616990
TI - Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal
Activation?
AB - Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem,
from where it is released by axonal varicosities throughout the brain via volume
transmission. A wealth of data from clinics and from animal models indicates that
this catecholamine coordinates the activity of the central nervous system (CNS)
and of the whole organism by modulating cell function in a vast number of brain
areas in a coordinated manner. The ubiquity of NE receptors, the daunting number
of cerebral areas regulated by the catecholamine, as well as the variety of
cellular effects and of their timescales have contributed so far to defeat the
attempts to integrate central adrenergic function into a unitary and coherent
framework. Since three main families of NE receptors are represented-in order of
decreasing affinity for the catecholamine-by: alpha2 adrenoceptors (alpha2Rs,
high affinity), alpha1 adrenoceptors (alpha1Rs, intermediate affinity), and beta
adrenoceptors (betaRs, low affinity), on a pharmacological basis, and on the
ground of recent studies on cellular and systemic central noradrenergic effects,
we propose that an increase in LC tonic activity promotes the emergence of four
global states covering the whole spectrum of brain activation: (1) sleep: virtual
absence of NE, (2) quiet wake: activation of alpha2Rs, (3) active
wake/physiological stress: activation of alpha2- and alpha1-Rs, (4) distress:
activation of alpha2-, alpha1-, and beta-Rs. We postulate that excess intensity
and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing
in turn-a variety of neuropsychiatric illnesses including depression,
schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay
between tonic and phasic LC activity identified in the LC in relationship with
behavioral response is of critical importance in defining the short- and long
term biological mechanisms associated with the basic states postulated for the
CNS. While the model has the potential to explain a large number of experimental
and clinical findings, a major challenge will be to adapt this hypothesis to
integrate the role of other neurotransmitters released during stress in a
centralized fashion, like serotonin, acetylcholine, and histamine, as well as
those released in a non-centralized fashion, like purines and cytokines.
PMID- 27616998
TI - Executive Functions in Children Who Experience Bullying Situations.
AB - Bullying is characterized by intentional, repetitive, and persistent aggressive
behavior that causes damage to the victim. Many studies investigate the social
and emotional aspects related to bullying, but few assess the cognitive aspects
it involves. Studies with aggressive individuals indicate impairment in executive
functioning and decision-making. The objective of this study was to assess hot
and cold executive functions in children who experience bullying. A total of 60
children between 10 and 11 years of age were included in the study. They were
divided into four groups: aggressors (bullies), victims, bully-victims, and
control. Tests for decision-making, inhibitory control, working memory, and
cognitive flexibility were used. The bully group made more unfavorable choices on
the Iowa Gambling Task, which may indicate difficulties in the decision-making
process. The victim group took longer to complete the Trail Making Test (Part B)
than aggressors, suggesting lower cognitive flexibility in victims. The
hypothesis that aggressors would have lower performance in other executive
functions such as inhibitory control, working memory, and cognitive flexibility
has not been confirmed. This study indicates that bullies have an impairment of
hot executive functions whereas victims have a comparatively lower performance in
cold executive functions. In addition to social and cultural variables,
neurocognitive and emotional factors seem to influence the behavior of children
in bullying situations.
PMID- 27616996
TI - Utility of Washington Early Recognition Center Self-Report Screening
Questionnaires in the Assessment of Patients with Schizophrenia and Bipolar
Disorder.
AB - Early identification and treatment are associated with improved outcomes in
bipolar disorder (BPD) and schizophrenia (SCZ). Screening for the presence of
these disorders usually involves time-intensive interviews that may not be
practical in settings where mental health providers are limited. Thus,
individuals at earlier stages of illness are often not identified. The Washington
Early Recognition Center Affectivity and Psychosis (WERCAP) screen is a self
report questionnaire originally developed to identify clinical risk for
developing bipolar or psychotic disorders. The goal of the current study was to
investigate the utility of the WERCAP Screen and two complementary
questionnaires, the WERC Stress Screen and the WERC Substance Screen, in
identifying individuals with established SCZ or BPD. Participants consisted of 35
BPD and 34 SCZ patients, as well as 32 controls (CON), aged 18-30 years.
Univariate analyses were used to test for score differences between groups.
Logistic regression and receiver operating characteristic (ROC) curves were used
to identify diagnostic predictors. Significant group differences were found for
the psychosis section of the WERCAP (pWERCAP; p < 0.001), affective section of
the WERCAP (aWERCAP; p = 0.001), and stress severity (p = 0.027). No significant
group differences were found in the rates of substance use as measured by the
WERC Substance Screen (p = 0.267). Only the aWERCAP and pWERCAP scores were
useful predictors of diagnostic category. ROC curve analysis showed the optimal
cut point on the aWERCAP to identify BPD among our participant groups was a score
of >20 [area under the curve (AUC): 0.87; sensitivity: 0.91; specificity: 0.71],
while that for the pWERCAP to identify SCZ was a score of >13 (AUC: 0.89;
sensitivity: 0.88; specificity: 0.82). These results indicate that the WERCAP
Screen may be useful in screening individuals for BPD and SCZ and that
identifying stress and substance-use severity can be rapidly done using self
report questionnaires. Larger studies in undiagnosed individuals will be needed
to test the WERCAP Screen's ability to identify mania or psychosis in the
community.
PMID- 27616997
TI - Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major
Depressive Disorder - Rationale, Design, and Characteristics of the Cognitive
Function and Mood Study (CoFaM-Study).
AB - Cross-sectional and longitudinal studies exploring clinical, functional, and
biological correlates of major depressive disorder are frequent. In this type of
research, depression is most commonly defined as a categorical diagnosis based on
studies using diagnostic instruments. Given the phenotypic and biological
heterogeneity of depression, we chose to focus the phenotypic assessments on
three cognitive dimensions of depression including (a) cognitive performance, (b)
emotion processing, and (c) social cognitive functioning. Hence, the overall aim
of the study is to investigate the long-term clinical course of these cognitive
dimensions in depression and its functional (psychosocial) correlates. We also
aim to identify biological "genomic" correlates of these three cognitive
dimensions of depression. To address the above overall aim, we created the
Cognition and Mood Study (CoFaMS) with the key objective to investigate the
clinical, functional, and biological correlates of cognitive dimensions of
depression by employing a prospective study design and including a healthy
control group. The study commenced in April 2015, including patients with a
primary diagnosis of a major depressive episode of major depressive disorder or
bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three
cognitive dimensions of depression (cognitive performance, emotion processing,
and social cognition), cognitive function screening instrument, plus functional
scales to assess general, work place, and psychosocial function, depression
symptom scales, and clinical course of illness. Blood is collected for
comprehensive genomic discovery analyses of biological correlates of cognitive
dimensions of depression. The CoFaM-Study represents an innovative approach
focusing on cognitive dimensions of depression and its functional and biological
"genomic" correlates. The CoFaMS team welcomes collaborations with both national
and international researchers.
PMID- 27616999
TI - How Online Basic Psychological Need Satisfaction Influences Self-Disclosure
Online among Chinese Adolescents: Moderated Mediation Effect of Exhibitionism and
Narcissism.
AB - Under the basic framework of self-determination theory, the present study
examined a moderated mediation model in which exhibitionism mediated the
relationship between online basic psychological need satisfaction and self
disclosure on the mobile Internet, and this mediation effect was moderated by
narcissism. A total of 296 Chinese middle school students participated in this
research. The results revealed that exhibitionism fully mediated the association
between online competence need satisfaction and self-disclosure on the mobile
net, and partly mediated the association between online relatedness need
satisfaction and self-disclosure on the mobile net. The mediating path from
online basic psychological need satisfaction (competence and relatedness) to
exhibitionism was moderated by narcissism. Compared to the low level of
narcissism, online competence need satisfaction had a stronger predictive power
on exhibitionism under the high level of narcissism condition. In contrast,
online relatedness need satisfaction had a weaker predictive power on
exhibitionism.
PMID- 27617001
TI - The Biologically-Based Bias of Personality Disorder Diagnosis.
PMID- 27617000
TI - The Spawns of Creative Behavior in Team Sports: A Creativity Developmental
Framework.
AB - Developing creativity in team sports players is becoming an increasing focus in
sports sciences. The Creativity Developmental Framework is presented to provide
an updated science based background. This Framework describes five incremental
creative stages (beginner, explorer, illuminati, creator, and rise) and combines
them into multidisciplinary approaches embodied in creative assumptions. In the
first training stages, the emphasis is placed on the enrollment in
diversification, deliberate play and physical literacy approaches grounded in
nonlinear pedagogies. These approaches allow more freedom to discover different
movement patterns increasing the likelihood of emerging novel, adaptive and
functional solutions. In the later stages, the progressive specialization in
sports and the differential learning commitment are extremely important to push
the limits of the creative progress at higher levels of performance by increasing
the range of skills configurations. Notwithstanding, during all developmental
stages the teaching games for understanding, a game-centered approach, linked
with the constraints-led approach play an important role to boost the tactical
creative behavior. Both perspectives might encourage players to explore all
actions possibilities (improving divergent thinking) and prevents the
standardization in their actions. Overall, considering the aforementioned
practice conditions the Creativity Developmental Framework scrutinizes the main
directions that lead to a long-term improvement of the creative behavior in team
sports. Nevertheless, this framework should be seen as a work in progress to be
later used as the paramount reference in creativity training.
PMID- 27617002
TI - Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of
Stroke.
AB - Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently
approved by the FDA for the treatment of multiple sclerosis. Currently, there is
a significant interest in the potential benefits of FTY720 on stroke outcomes.
FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous
presence in the central nervous system and both rodent models and pilot clinical
trials seem to indicate that the drug may improve overall functional recovery in
different stroke subtypes. Although the precise mechanisms behind these
beneficial effects are yet unclear, there is evidence that FTY720 has a role in
regulating cerebrovascular responses, blood-brain barrier permeability, and cell
survival in the event of cerebrovascular insult. In this article, we critically
review the data obtained from the latest laboratory findings and clinical trials
involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive
picture of FTY720's mechanisms of action in stroke.
PMID- 27617003
TI - Effects of Gadolinium-Based Contrast Agents on Thyroid Hormone Receptor Action
and Thyroid Hormone-Induced Cerebellar Purkinje Cell Morphogenesis.
AB - Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to
enhance the quality of magnetic resonance imaging or angiography. After
intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs)
are critical for the development and functional maintenance of the central
nervous system. TH actions in brain are mainly exerted through nuclear TH
receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in
CV-1 cells using transient transfection-based reporter assay and TH-mediated
cerebellar Purkinje cell morphogenesis in primary culture. We also measured the
cellular accumulation and viability of Gd after representative GBCA treatments in
cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis
methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic
acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells.
By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher
Gd accumulation and significantly reduced the number of cells. Low doses of Gd
DTPA-BMA (10(-8) to 10(-6)M) augmented TR-mediated transcription, but the
transcription was suppressed at higher dose (10(-5) to 10(-4)M), with decreased
beta-galactosidase activity indicating cellular toxicity. TR-mediated
transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a
significant reduction in beta-galactosidase activity at high doses, indicating
cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje
cells induced by 10(-9)M T4 was augmented by low-dose Gd-DTPA-BMA (10(-7)M) but
was suppressed by higher dose (10(-5)M). Such augmentation by low-dose Gd-DTPA
BMA was not observed with 10(-9)M T3, probably because of the greater dendrite
arborization by T3; however, the arborization by T3 was suppressed by a higher
dose of Gd-DTPA-BMA (10(-5)M) as seen in T4 treatment. The effect of Gd-DOTA on
dendrite arborization was much weaker than that of the other compounds. These
results indicate that exposure to specific GBCAs may, at least in part, cause
toxic effects in the brain by disrupting the action of THs on TRs. The toxic
effects of GBCAs may depend on the chemical structure of GBCA and the dose. Thus,
it is very important to choose appropriate GBCAs for imaging to prevent adverse
side effects.
PMID- 27617004
TI - Whole Genome Sequencing of Enterovirus species C Isolates by High-Throughput
Sequencing: Development of Generic Primers.
AB - Enteroviruses are among the most common viruses infecting humans and can cause
diverse clinical syndromes ranging from minor febrile illness to severe and
potentially fatal diseases. Enterovirus species C (EV-C) consists of more than 20
types, among which the three serotypes of polioviruses, the etiological agents of
poliomyelitis, are included. Biodiversity and evolution of EV-C genomes are
shaped by frequent recombination events. Therefore, identification and
characterization of circulating EV-C strains require the sequencing of different
genomic regions. A simple method was developed to quickly sequence the entire
genome of EV-C isolates. Four overlapping fragments were produced separately by
RT-PCR performed with generic primers. The four amplicons were then pooled and
purified prior to being sequenced by a high-throughput technique. The method was
assessed on a panel of EV-Cs belonging to a wide-range of types. It can be used
to determine full-length genome sequences through de novo assembly of thousands
of reads. It was also able to discriminate reads from closely related viruses in
mixtures. By decreasing the workload compared to classical Sanger-based
techniques, this method will serve as a precious tool for sequencing large panels
of EV-Cs isolated in cell cultures during environmental surveillance or from
patients, including vaccine-derived polioviruses.
PMID- 27617006
TI - Enzymatic Strategies and Carbon Use Efficiency of a Litter-Decomposing Fungus
Grown on Maize Leaves, Stems, and Roots.
AB - Soil microorganisms can control the soil cycles of carbon (C), and depending on
their C-use efficiency (CUE), these microorganisms either contribute to C
stabilization in soil or produce CO2 when decomposing organic matter. However,
little is known regarding the enzyme investment of microbial decomposers and the
effects on their CUE. Our objective was to elucidate the strategies of litter
decomposing fungi as a function of litter quality. Fungal biosynthesis and
respiration were accounted for by quantifying the investment in enzyme synthesis
and enzyme efficiency. The basidiomycete Phanerochaete chrysosporium was grown on
the leaves, stems, and roots of maize over 126 days in controlled conditions. We
periodically measured the fungal biomass, enzyme activity, and chemical
composition of the remaining litter and continuously measured the evolved C-CO2.
The CUE observed for the maize litter was highest in the leaves (0.63),
intermediate in the roots (0.40), and lowest in the stems (0.38). However, the
enzyme efficiency and investment in enzyme synthesis did not follow the same
pattern. The amount of litter C decomposed per mole of C-acquiring hydrolase
activity was 354 MUg C in the leaves, 246 MUg C in the roots, and 1541 MUg C in
the stems (enzyme efficiency: stems > leaves > roots). The fungus exhibited the
highest investment in C-acquiring enzyme when grown on the roots and produced 40
80% less enzyme activity when grown on the stems and leaves (investment in
enzymes: roots > leaves > stems). The CUE was dependent on the initial
availability and replenishment of the soluble substrate fraction with the
degradation products. The production of these compounds was either limited
because of the low enzyme efficiency, which occurred in the roots, or because of
the low investments in enzyme synthesis, which occurred in the stems. Fungal
biosynthesis relied on the ability of the fungus to invest in enzyme synthesis
and the efficient interactions between the enzymes and the substrate. The
investment decreased when N was limited, whereas the efficiency of the C
acquiring enzymes was primarily explained by the hemicellulose content and its
embedment in recalcitrant lignin linkages. Our results are crucial for modeling
microbial allocation strategies.
PMID- 27617005
TI - Pseudopyronine B: A Potent Antimicrobial and Anticancer Molecule Isolated from a
Pseudomonas mosselii.
AB - In continuation of our search for new bioactive compounds from soil microbes, a
fluorescent Pseudomonas strain isolated from paddy field soil of Kuttanad,
Kerala, India was screened for the production of bioactive secondary metabolites.
This strain was identified as Pseudomonas mosselii through 16S rDNA gene
sequencing followed by BLAST analysis and the bioactive metabolites produced were
purified by column chromatography (silica gel) and a pure bioactive secondary
metabolite was isolated. This bioactive compound was identified as Pseudopyronine
B by NMR and HR-ESI-MS. Pseudopyronine B recorded significant antimicrobial
activity especially against Gram-positive bacteria and agriculturally important
fungi. MTT assay was used for finding cell proliferation inhibition, and
Pseudopyronine B recorded significant antitumor activity against non-small cell
lung cancer cell (A549), and mouse melanoma cell (B16F10). The preliminary MTT
assay results revealed that Pseudopyronine B recorded both dose- and time
dependent inhibition of the growth of test cancer cell lines. Pseudopyronine B
induced apoptotic cell death in cancer cells as evidenced by Acridine
orange/ethidium bromide and Hoechst staining, and this was further confirmed by
flow cytometry analysis using Annexin V. Cell cycle analysis also supports
apoptosis by inducing G2/M accumulation in both A549 and B16F10 cells.
Pseudopyronine B treated cells recorded significant up-regulation of caspase 3
activity. Moreover, this compound recorded immunomodulatory activity by enhancing
the proliferation of lymphocytes. The production of Pseudopyronine B by P.
mosselii and its anticancer activity in A549 and B16F10 cell lines is reported
here for the first time. The present study has a substantial influence on the
information of Pseudopyronine B from P. mosselii as potential sources of novel
drug molecule for the pharmaceutical companies, especially as potent
antimicrobial and anticancer agent.
PMID- 27617008
TI - Using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF)
Complemented with Selected 16S rRNA and gyrB Genes Sequencing to Practically
Identify Clinical Important Viridans Group Streptococci (VGS).
AB - There are challenges in viridans group streptococci (VGS) identification
especially for the mitis group. Few studies have investigated the performance of
MALDI-TOF MS system in VGS identification. Using 16S rRNA gene and gyrB gene
sequencing as a gold standard, the performance of two MALDI-TOF MS instruments in
the identification of 181 VGS clinical isolates was studied. The Bruker Biotyper
and Vitek MS IVD systems correctly identified 88.4% and 98.9% of the 181
isolates, respectively. The Vitek MS RUO system was the least reliable, only
correctly identifying 38.7% of the isolates to species level with several
misidentifications and invalid results. The Bruker Biotyper system was very
unreliable in the identification of species within the mitis group. Among 22 non
pneumococci isolates (S. mitis/S. oralis/S. pseudopneumoniae), Biotyper
misidentified 21 of them as S. pneumoniae leading to a low sensitivity and low
positive predictive value in these species. In contrast, the Vitek MS IVD
demonstrated a better resolution for pneumococci and non-pneumococci despite the
inability to distinguish between S. mitis/S. oralis. For more accurate species
level identification, further improvements in the VGS spectra databases are
needed. Based on MALDI-TOF analysis and selected 16S rRNA gene plus gyrB genes
sequencing, we designed a practical VGS identification algorithm.
PMID- 27617007
TI - Next-Generation Sequencing and Genome Editing in Plant Virology.
AB - Next-generation sequencing (NGS) has been applied to plant virology since 2009.
NGS provides highly efficient, rapid, low cost DNA, or RNA high-throughput
sequencing of the genomes of plant viruses and viroids and of the specific small
RNAs generated during the infection process. These small RNAs, which cover
frequently the whole genome of the infectious agent, are 21-24 nt long and are
known as vsRNAs for viruses and vd-sRNAs for viroids. NGS has been used in a
number of studies in plant virology including, but not limited to, discovery of
novel viruses and viroids as well as detection and identification of those
pathogens already known, analysis of genome diversity and evolution, and study of
pathogen epidemiology. The genome engineering editing method, clustered regularly
interspaced short palindromic repeats (CRISPR)-Cas9 system has been successfully
used recently to engineer resistance to DNA geminiviruses (family, Geminiviridae)
by targeting different viral genome sequences in infected Nicotiana benthamiana
or Arabidopsis plants. The DNA viruses targeted include tomato yellow leaf curl
virus and merremia mosaic virus (begomovirus); beet curly top virus and beet
severe curly top virus (curtovirus); and bean yellow dwarf virus (mastrevirus).
The technique has also been used against the RNA viruses zucchini yellow mosaic
virus, papaya ringspot virus and turnip mosaic virus (potyvirus) and cucumber
vein yellowing virus (ipomovirus, family, Potyviridae) by targeting the
translation initiation genes eIF4E in cucumber or Arabidopsis plants. From these
recent advances of major importance, it is expected that NGS and CRISPR-Cas
technologies will play a significant role in the very near future in advancing
the field of plant virology and connecting it with other related fields of
biology.
PMID- 27617009
TI - Suilysin Stimulates the Release of Heparin Binding Protein from Neutrophils and
Increases Vascular Permeability in Mice.
AB - Most of the deaths that occurred during two large outbreaks of Streptococcus suis
infections in 1998 and 2005 in China were caused by streptococcal toxic shock
syndrome (STSS), which is characterized by increased vascular permeability.
Heparin-binding protein (HBP) is thought to mediate the vascular leakage. The
purpose of this study was to investigate the detailed mechanism underlying the
release of HBP and the vascular leakage induced by S. suis. Significantly higher
serum levels of HBP were detected in Chinese patients with STSS than in patients
with meningitis or healthy controls. Suilysin (SLY) is an exotoxin secreted by
the highly virulent strain 05ZYH33, and it stimulated the release of HBP from the
polymorphonuclear neutrophils and mediated vascular leakage in mice. The release
of HBP induced by SLY was caused by a calcium influx-dependent degranulation.
Analyses using a pharmacological approach revealed that the release of HBP
induced by SLY was related to Toll-like receptor 4, p38 mitogen-activated protein
kinase, and the 1-phosphatidylinositol 3-kinase pathway. It was also dependent on
a G protein-coupled seven-membrane spanning receptor. The results of this study
provide new insights into the vascular leakage in STSS associated with non-Group
A streptococci, which could lead to the discovery of potential therapeutic
targets for STSS associated with S. suis.
PMID- 27617010
TI - Nitrogen Fixation and Molecular Oxygen: Comparative Genomic Reconstruction of
Transcription Regulation in Alphaproteobacteria.
AB - Biological nitrogen fixation plays a crucial role in the nitrogen cycle. An
ability to fix atmospheric nitrogen, reducing it to ammonium, was described for
multiple species of Bacteria and Archaea. The transcriptional regulatory network
for nitrogen fixation was extensively studied in several representatives of the
class Alphaproteobacteria. This regulatory network includes the activator of
nitrogen fixation NifA, working in tandem with the alternative sigma-factor RpoN
as well as oxygen-responsive regulatory systems, one-component regulators
FnrN/FixK and two-component system FixLJ. Here we used a comparative genomics
approach for in silico study of the transcriptional regulatory network in 50
genomes of Alphaproteobacteria. We extended the known regulons and proposed the
scenario for the evolution of the nitrogen fixation transcriptional network. The
reconstructed network substantially expands the existing knowledge of
transcriptional regulation in nitrogen-fixing microorganisms and can be used for
genetic experiments, metabolic reconstruction, and evolutionary analysis.
PMID- 27617011
TI - An Improved Culture Method for Selective Isolation of Campylobacter jejuni from
Wastewater.
AB - Campylobacter jejuni is one of the leading foodborne pathogens worldwide. C.
jejuni is isolated from a wide range of foods, domestic animals, wildlife, and
environmental sources. The currently available culture-based isolation methods
are not highly effective for wastewater samples due to the low number of C.
jejuni in the midst of competing bacteria. To detect and isolate C. jejuni from
wastewater samples, in this study, we evaluated a few different enrichment
conditions using five different antibiotics (i.e., cefoperazone, vancomycin,
trimethoprim, polymyxin B, and rifampicin), to which C. jejuni is intrinsically
resistant. The selectivity of each enrichment condition was measured with C t
value using quantitative real-time PCR, and multiplex PCR to determine
Campylobacter species. In addition, the efficacy of Campylobacter isolation on
different culture media after selective enrichment was examined by growing on
Bolton and Preston agar plates. The addition of polymyxin B, rifampicin, or both
to the Bolton selective supplements enhanced the selective isolation of C.
jejuni. The results of 16S rDNA sequencing also revealed that Enterococcus spp.
and Pseudomonas aeruginosa are major competing bacteria in the enrichment
conditions. Although it is known to be difficult to isolate Campylobacter from
samples with heavy contamination, this study well exhibited that the manipulation
of antibiotic selective pressure improves the isolation efficiency of fastidious
Campylobacter from wastewater.
PMID- 27617012
TI - Dispersion of the Vancomycin Resistance Genes vanA and vanC of Enterococcus
Isolated from Nile Tilapia on Retail Sale: A Public Health Hazard.
AB - Although normally regarded harmless commensals, enterococci may cause a range of
different infections in humans, including urinary tract infections, sepsis, and
endocarditis. The acquisition of vancomycin resistance by enterococci (VRE) has
seriously affected the treatment and infection control of these organisms. VRE
are frequently resistant to all antibiotics that are effective treatment for
vancomycin-susceptible enterococci, which leaves clinicians treating VRE
infections with limited therapeutic options. With VRE emerging as a global threat
to public health, we aimed to isolate, identify enterococci species from tilapia
and their resistance to van-mediated glycopeptide (vanA and vanC) as well as the
presence of enterococcal surface protein (esp) using conventional and molecular
methods. The cultural, biochemical (Vitek 2 system) and polymerase chain reaction
results revealed eight Enterococcus isolates from the 80 fish samples (10%) to be
further identified as E. faecalis (6/8, 75%) and E gallinarum (2/8, 25%).
Intraperitoneal injection of healthy Nile tilapia with the eight Enterococcus
isolates caused significant morbidity (70%) within 3 days and 100% mortality at 6
days post-injection with general signs of septicemia. All of the eight
Enterococcus isolates were found to be resistant to tetracycline. The 6/6 E.
faecalis isolates were susceptible for penicillin, nitrofurantoin, gentamicin,
and streptomycin. On the other hand 5/6 were susceptible for ampicillin,
vancomycin, chloramphenicol, and ciprofloxacin. The two isolates of E. gallinarum
were sensitive to rifampicin and ciprofloxacin and resistant to vancomycin,
chloramphenicol, and erythromycin. Molecular characterization proved that they
all presented the prototypic vanC element. On the whole, one of the two
vancomycin resistance gene was present in 3/8 of the enterococci isolates, while
the esp virulence gene was present in 1/8 of the enterococci isolates. The
results in this study emphasize the potential role that aquatic environments are
correlated to proximity to anthropogenic activities in determining the
antimicrobial resistance patterns of Enterococcus spp. recovered from fish in the
river Nile in Giza, Elmounib, Egypt as a continuation of our larger study on the
reservoirs of antibiotic resistance in the environment.
PMID- 27617013
TI - Human Transbodies to HCV NS3/4A Protease Inhibit Viral Replication and Restore
Host Innate Immunity.
AB - A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still
needed. In this study, human single chain variable fragments of antibody (scFvs)
that bound to HCV NS3/4A protein were produced by phage display technology. The
engineered scFvs were linked to nonaarginines (R9) for making them cell
penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced
from four different transformed E. coli clones had reduced HCV-RNA inside the
cells and in the cell spent media, as well as fewer HCV foci in the cell
monolayer compared to the transfected cells in culture medium alone. The
transbodies-treated transfected cells also had up-expression of the genes coding
for the host innate immune response, including TRIF, TRAF3, IRF3, IL-28B, and IFN
beta. Computerized homology modeling and intermolecular docking predicted that
the effective transbodies interacted with several critical residues of the NS3/4A
protease, including those that form catalytic triads, oxyanion loop, and S1 and
S6 pockets, as well as a zinc-binding site. Although insight into molecular
mechanisms of the transbodies need further laboratory investigation, it can be
deduced from the current data that the transbodies blocked the HCV NS3/4A
protease activities, leading to the HCV replication inhibition and restoration of
the virally suppressed host innate immunity. The engineered antibodies should be
tested further for treatment of HCV infection either alone, in combination with
current therapeutics, or in a mixture with their cognates specific to other HCV
proteins.
PMID- 27617015
TI - NETosis - Does It Really Represent Nature's "Suicide Bomber"?
PMID- 27617014
TI - Neutrophil Extracellular Traps Enhance Early Inflammatory Response in Sendai
Virus-Induced Asthma Phenotype.
AB - Paramyxoviral infection in childhood has been linked to a significant increased
rate of asthma development. In mice, paramyxoviral infection with the mouse
parainfluenza virus type I, Sendai virus (Sev), causes a limited bronchiolitis
followed by persistent asthma traits. We have previously shown that the absence
of cysteine protease dipeptidyl peptidase I (DPPI) dampened the acute lung
inflammatory response and the subsequent asthma phenotype induced by Sev.
Adoptive transfer of wild-type neutrophils into DPPI-deficient mice restored
leukocyte influx, the acute cytokine response, and the subsequent mucous cell
metaplasia that accompanied Sev-induced asthma phenotype. However, the exact
mechanism by which DPPI-sufficient neutrophils promote asthma development
following Sev infection is still unknown. We hypothesize that neutrophils
recruited to the alveolar space following Sev infection elaborate neutrophil
extracellular traps (NETs) that propagate the inflammatory cascade, culminating
in the eventual asthma phenotype. Indeed, we found that Sev infection was
associated with NET formation in the lung and release of cell-free DNA complexed
to myeloperoxidase in the alveolar space and plasma that peaked on day 2 post
infection. Absence of DPPI significantly attenuated Sev-induced NET formation in
vivo and in vitro. Furthermore, concomitant administration of DNase 1, which
dismantled NETs, or inhibition of peptidylarginine deiminase 4 (PAD4), an
essential mediator of NET formation, suppressed the early inflammatory responses
to Sev infection. Lastly, NETs primed bone marrow-derived cells to release
cytokines that can amplify the inflammatory cascade.
PMID- 27617016
TI - Fine Root Productivity and Turnover of Ectomycorrhizal and Arbuscular Mycorrhizal
Tree Species in a Temperate Broad-Leaved Mixed Forest.
AB - Advancing our understanding of tree fine root dynamics is of high importance for
tree physiology and forest biogeochemistry. In temperate broad-leaved forests,
ectomycorrhizal (EM) and arbuscular mycorrhizal (AM) tree species often are
coexisting. It is not known whether EM and AM trees differ systematically in fine
root dynamics and belowground resource foraging strategies. We measured fine root
productivity (FRP) and fine root turnover (and its inverse, root longevity) of
three EM and three AM broad-leaved tree species in a natural cool-temperate mixed
forest using ingrowth cores and combined the productivity data with data on root
biomass per root orders. FRP and root turnover were related to root morphological
traits and aboveground productivity. FRP differed up to twofold among the six
coexisting species with larger species differences in lower horizons than in the
topsoil. Root turnover varied up to fivefold among the species with lowest values
in Acer pseudoplatanus and highest in its congener Acer platanoides. Variation in
root turnover was larger within the two groups than between EM and AM species. We
conclude that the main determinant of FRP and turnover in this mixed forest is
species identity, while the influence of mycorrhiza type seems to be less
important.
PMID- 27617017
TI - A Meta-Analysis of the Impact of Anaerobic Soil Disinfestation on Pest
Suppression and Yield of Horticultural Crops.
AB - Anaerobic soil disinfestation (ASD) is a proven but relatively new strategy to
control soil borne pests of horticultural crops through anaerobic decomposition
of organic soil amendments. The ASD technique has primarily been used to control
soil borne pathogens; however, this technique has also shown potential to control
plant parasitic nematodes and weeds. ASD can utilize a broad range of carbon (C)
amendments and optimization may improve efficacy across environments. In this
context, a meta-analysis using a random-effects model was conducted to determine
effect sizes of the ASD effect on soil borne pathogens (533 studies), plant
parasitic nematodes (91 studies), and weeds (88 studies) compared with unamended
controls. Yield response to ASD was evaluated (123 studies) compared to unamended
and fumigated controls. We also examined moderator variables for environmental
conditions and amendments to explore the impact of these moderators on ASD
effectiveness on pests and yield. Across all pathogen types with the exception of
Sclerotinia spp., ASD studies show suppression of bacterial, oomycete and fungal
pathogens (59 to 94%). Pathogen suppression was effective under all environmental
conditions (50 to 94%) and amendment types (53 to 97%), except when amendments
were applied at rates less than 0.3 kg m(-2). The ASD effect ranged from 15 to
56% for nematode suppression and 32 to 81% for weed suppression, but these
differences were not significant. Significant nematode moderators included study
type, soil type, sampling depth, incubation period, and use of mixed amendments.
Weed suppression due to ASD showed significant heterogeneity for all
environmental conditions, confirming that these studies do not share a common
effect size. Total crop yield was not reduced by ASD when compared to a fumigant
control and yield was significantly higher (30%) compared to an unamended
control, suggesting ASD as a feasible option to maintain yield without chemical
soil fumigants. We conclude ASD is effective against soil borne pathogens and
while not conclusive due to a limited number of studies, we expect the same for
nematodes and weeds given observed effect sizes. Findings should assist
researchers in exploring ASD efficacy in particular environmental conditions and
allow for development of standard treatment protocols.
PMID- 27617018
TI - Dispersal of the Invasive Pasture Pest Heteronychus arator into Areas of Low
Population Density: Effects of Sex and Season, and Implications for Pest
Management.
AB - African black beetle, Heteronychus arator (Scarabaeidae), is an exotic pest of
pastures in northern New Zealand. Both adults and larvae feed on pasture grasses.
Adults disperse by walking (short range) or flying (long range). Dispersal
flights are triggered by warm night temperatures in spring and autumn. Short
range adult dispersal in search of mates, food or oviposition sites is poorly
understood. This study investigated walking activity of H. arator adults over
three seasons in New Zealand pastures. Adult walking activity was monitored using
pitfall traps along fence lines and in pasture plots on a dairy farm in Waikato,
New Zealand, in spring 2013, spring 2014, and autumn 2015. Beetle populations
were reduced by application of a biopesticide bait to compare walking activity
between treated and control plots for up to 26 days post-treatment. Marked
beetles were released into the pasture plots to measure the distance traveled by
recaptured individuals. Trap catches along the fence lines were correlated with
air temperatures in 2013. Trap catches were male biased in spring 2014 compared
with autumn 2015. Trap numbers in the control plots were nearly double that of
treated plots in both seasons. More beetles were caught in the pitfall traps at
the edges of the treated plots than in the center. Trap catches were consistent
throughout the control plot in spring 2014, but in autumn 2015 more beetles were
caught in the center of the control plot than at the edges. Few marked beetles
were recaptured with dispersal rates estimated as <0.5 m per day. Warmer
temperatures encouraged short range dispersal in H. arator. Males were more
active than females during the spring mating season. Edge effects were strong and
should be considered in the design of field experiments.
PMID- 27617019
TI - Association Mapping of Main Tomato Fruit Sugars and Organic Acids.
AB - Association mapping has been widely used to map the significant associated loci
responsible for natural variation in complex traits and are valuable for crop
improvement. Sugars and organic acids are the most important metabolites in
tomato fruits. We used a collection of 174 tomato accessions composed of Solanum
lycopersicum (123 accessions) and S. lycopersicum var cerasiforme (51 accessions)
to detect significantly associated loci controlling the variation of main sugars
and organic acids. The accessions were genotyped with 182 SSRs spreading over the
tomato genome. Association mapping was conducted on the main sugars and organic
acids detected by gas chromatography-mass spectrometer (GC-MS) over 2 years using
the mixed linear model (MLM). We detected a total of 58 significantly associated
loci (P < 0.001) for the 17 sugars and organic acids, including fructose,
glucose, sucrose, citric acid, malic acid. These results not only co-localized
with several reported QTLs, including fru9.1/PV, suc9.1/PV, ca2.1/HS, ca3.1/PV,
ca4.1/PV, and ca8.1/PV, but also provided a list of candidate significantly
associated loci to be functionally validated. These significantly associated loci
could be used for deciphering the genetic architecture of tomato fruit sugars and
organic acids and for tomato quality breeding.
PMID- 27617020
TI - Quantitative Understanding of Nanoparticle Uptake in Watermelon Plants.
AB - The use of agrochemical-nutrient fertilizers has come under scrutiny in recent
years due to concerns that they damage the ecosystem and endanger public health.
Nanotechnology offers many possible interventions to mitigate these risks by use
of nanofertilizers, nanopesticides, and nanosensors; and concurrently increases
profitability, yields, and sustainability within the agricultural industry.
Aerosol based foliar delivery of nanoparticles may help to enhance nanoparticle
uptake and reduce environmental impacts of chemical fertilizers conventionally
applied through a soil route. The purpose of this work was to study uptake,
translocation, and accumulation of various gold nanostructures, 30-80 nm,
delivered by aerosol application to a watermelon plant. Cellular uptake and
accumulation of gold nanoparticles were quantified by Inductively Coupled Plasma
Mass Spectroscopy (ICP-MS). Observations suggested that nanoparticles could be
taken up by the plant through direct penetration and transport through the
stomatal opening. Observed translocation of nanoparticles from leaf to root shows
evidence that nanoparticles travel by the phloem transport mechanism.
Accumulation and transport of nanoparticles depend on nanoparticle shape,
application method, and nature of plant tissues.
PMID- 27617022
TI - Heterologous expression, protein folding and antibody recognition of a neurotoxin
from the Mexican coral snake Micrurus laticorallis.
AB - BACKGROUND: The cysteine-rich neurotoxins from elapid venoms are primarily
responsible for human and animal envenomation; however, their low concentration
in the venom may hamper the production of efficient elapid antivenoms. Therefore,
the aim of the present study was to produce fully active elapid neurotoxic
immunogens for elapid antivenom production. METHOD: Cysteine-rich neurotoxins
showed recombinant expression in two strains of E. coli, and were purified using
affinity chromatography and reverse-phase HPLC (rpHPLC). RESULTS: The cDNA of the
four disulfide-bridged peptide neurotoxin Mlat1 was cloned into a modified
expression vector, pQE30, which was transfected into two different E. coli
strains. The recombinant toxin (HisrMlat1) was found only in inclusion bodies in
M15 strain cells, and in both inclusion bodies and cytoplasm in Origami strain
cells. The HisrMlat1 from inclusion bodies from M15 cells was solubilized using
guanidine hydrochloride, and then purified by rpHPLC. It showed various
contiguous fractions having the same molecular mass, indicating that HisrMlat1
was oxidized after cell extraction forming different misfolded disulfide bridge
arrangements without biological activity. In vitro folding conditions of the
misfolded HisrMlat1 generated a biologically active HisrMlat1. On the other hand,
the HisrMlat1 from the cytoplasm from Origami cells was already soluble, and then
purified by HPLC. It showed a single fraction with neurotoxic activity; so, no
folding steps were needed. The in vitro folded HisrMlat1 from M15 cells and the
cytoplasmic soluble HisrMlat1from Origami cells were indistinguishable in their
structure and neurotoxicity. Rabbit polyclonal antibodies raised up against
biologically active HisrMlat1 recognized the native Mlat1 (nMlat1) from the whole
venom of M. laticorallis. In addition, HisrMlat1 was recognized by horse
polyclonal antibodies obtained from the immunization of elapid species from sub
Saharan Africa. CONCLUSION: HisrMlat1 shows increased biological activities
compared to the native peptide, and may be used as an immunizing agent in
combination with other toxic components such phospholipases type A2 for elapid
antivenom production.
PMID- 27617021
TI - Regulatory Cross-Talks and Cascades in Rice Hormone Biosynthesis Pathways
Contribute to Stress Signaling.
AB - Crosstalk among different hormone signaling pathways play an important role in
modulating plant response to both biotic and abiotic stress. Hormone activity is
controlled by its bio-availability, which is again influenced by its
biosynthesis. Thus, independent hormone biosynthesis pathways must be regulated
and co-ordinated to mount an integrated response. One of the possibilities is to
use cis-regulatory elements to orchestrate expression of hormone biosynthesis
genes. Analysis of CREs, associated with differentially expressed hormone
biosynthesis related genes in rice leaf under Magnaporthe oryzae attack and
drought stress enabled us to obtain insights about cross-talk among hormone
biosynthesis pathways at the transcriptional level. We identified some master
transcription regulators that co-ordinate different hormone biosynthesis pathways
under stress. We found that Abscisic acid and Brassinosteroid regulate Cytokinin
conjugation; conversely Brassinosteroid biosynthesis is affected by both Abscisic
acid and Cytokinin. Jasmonic acid and Ethylene biosynthesis may be modulated by
Abscisic acid through DREB transcription factors. Jasmonic acid or Salicylic acid
biosynthesis pathways are co-regulated but they are unlikely to influence each
others production directly. Thus, multiple hormones may modulate hormone
biosynthesis pathways through a complex regulatory network, where biosynthesis of
one hormone is affected by several other contributing hormones.
PMID- 27617023
TI - Early infant diagnosis of HIV infection using DNA-PCR at a referral center: an 8
years retrospective analysis.
AB - BACKGROUND: Over the last decade, Ethiopia adopted different strategies of
prevention of mother to child transmission of HIV (PMTCT). Prior to
implementation of Option A in 2011, there was no provision of prophylaxis for
PMTCT. With 'Option A', PMTCT interventions relied on maternal CD4 count. In
early 2013, ''Option B+'' has been started; with this option, antiretroviral
therapy is started and continued for life to any HIV positive pregnant mother
irrespective of CD4 count with an enhanced treatment for the baby. Though there
are a number of studies which evaluated the effectiveness of PMTCT interventions,
the current study assessed the real-world effectiveness of PMTCT options in a
setting where there is limitation of resources. OBJECTIVE: This study tried to
address three questions: what proportion of babies tested by DNA-PCR are HIV
infected in the first 2 months of life? How does the type of PMTCT intervention
affect presence of HIV infection at this age? What are the factors affecting HIV
transmission, after controlling for type of PMCT-HIV intervention? METHODS: We
assessed records of 624 registered HIV exposed infants and 412 mothers who were
delivered at Bishoftu Hospital from May 2006 to August 2014. Presence of HIV
infection at 6-8 weeks of age was assessed from the records. Maternal and infant
risk factors for infection at this age were analyzed. Data were collected using
standard data abstraction format and were analyzed using SPSS version 20.
RESULTS: Among all the infants who were delivered at the hospital during the
study period, 624/936 (66.7 %) had undergone early infant diagnosis at 6-8 weeks.
Twenty-seven (4.3 %) were positive for HIV DNA PCR at the age of 6-8 weeks. None
of the infants who received ''Option B+'' had a positive HIV DNA PCR result. HIV
infection rate was highest among those who took either no prophylaxis or single
dose Nevirapine (11.5 and 11.1 % respectively). Those who took single dose
Nevirapine and Zidovudine had HIV positivity rate of 3.9 %. Many of the
covariates which were shown to be predictors on bivariate analysis were found not
to be independent predictors on multivariate analysis. CONCLUSION: PMTCT ''Option
B+'' resulted in zero HIV infection rates among the included infants. There was a
high loss to follow up rate at 6-8 weeks of age. The authors recommend that a
better strategy of linkage to care and treatment should be devised for HIV
exposed infants.
PMID- 27617025
TI - Holi colours contain PM10 and can induce pro-inflammatory responses.
AB - BACKGROUND: At Holi festivals, originally celebrated in India but more recently
all over the world, people throw coloured powder (Holi powder, Holi colour, Gulal
powder) at each other. Adverse health effects, i.e. skin and ocular irritations
as well as respiratory problems may be the consequences. The aim of this study
was to uncover some of the underlying mechanisms. METHODS: We analysed four
different Holi colours regarding particle size using an Electric field cell
counting system. In addition, we incubated native human cells with different Holi
colours and determined their potential to induce a pro-inflammatory response by
quantifying the resulting cytokine production by means of ELISA (Enzyme Linked
Immunosorbent Assay) and the resulting leukocyte oxidative burst by flow
cytometric analysis. Moreover, we performed the XTT (2,3-Bis-(2-methoxy-4-nitro-5
sulfophenyl)-2H-tetrazolium-5-carboxanilide) and Propidium iodide cytotoxicity
tests and we measured the endotoxin content of the Holi colour samples by means
of the Limulus Amebocyte Lysate test (LAL test). RESULTS: We show here that all
tested Holi colours consist to more than 40 % of particles with an aerodynamic
diameter smaller than 10 MUm, so called PM10 particles (PM, particulate matter).
Two of the analysed Holi powders contained even more than 75 % of PM10 particles.
Furthermore we demonstrate in cell culture experiments that Holi colours can
induce the production of the pro-inflammatory cytokines TNF-alpha (Tumor necrosis
factor-alpha), IL-6 (Interleukine-6) and IL-1beta (Interleukine-1beta). Three out
of the four analysed colours induced a significantly higher cytokine response in
human PBMCs (Peripheral Blood Mononuclear Cells) and whole blood than corn
starch, which is often used as carrier substance for Holi colours. Moreover we
show that corn starch and two Holi colours contain endotoxin and that certain
Holi colours display concentration dependent cytotoxic effects in higher
concentration. Furthermore we reveal that in principle Holi colours and corn
starch are able to generate an oxidative burst in human granulocytes and
monocytes. In Holi colour 1 we detected a fungal contamination. CONCLUSIONS: Some
of the observed unwanted health effects of Holi colours might be explained by the
high content of PM10 particles in conjunction with the possible induction of a
pro-inflammatory response and an oxidative leukocyte burst.
PMID- 27617024
TI - Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or
EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of
randomized controlled trials.
AB - BACKGROUND: The first-generation integrase inhibitors (INIs) raltegravir (RAL)
and elvitegravir (EVG) have shown efficacy against HIV infection, but they have
the limitations of once-more daily dosing and extensive cross-resistance.
Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such
shortcomings, is under spotlight. The purpose of this study is to review the
evidence for DTG use in clinical settings, including its efficacy and safety.
METHODS: PubMed, EMbase, Ovid, Web of Science, Science Direct, and related
websites were screened from establishment until July 2013, and scientific meeting
proceedings were manually searched. Two reviewers independently screened 118
citations repeatedly to identify randomized controlled trials comparing the
efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based
regimens. Using the selected studies with comparable outcome measures and
indications, we performed a meta-analysis based on modified intention-to-treat
(mITT), on-treatment (OT), and as-treated (AT) virological outcome data.
Independent data extraction and quality assessment were conducted. RESULTS: Four
unique studies were included with the use of DTG in antiretroviral therapy-naive
patients. In therapy-naive patients, DTG combined with abacavir/lamivudine
(ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better
virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence
interval (95 % CI 1.03-1.12). Evidence further supported use of DTG had a better
virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03
1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and
dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03-1.15; RR 1.06,
95 % CI 0.98-1.15, respectively). In the matter of safety of DTG-based regimen,
the risk of any event was RR 0.98 (95 % CI 0.94-1.01), the risk of serious
adverse events (AEs) was RR 0.84 (95 % CI 0.62-1.15), and the risk of drug
related serious AEs was RR 0.33 (95 % CI 0.13-0.79). CONCLUSION: In general, DTG
50 mg given once daily combined with an active background drug is a better choice
in terms of both efficacy and safety.
PMID- 27617028
TI - Shade tree diversity and aboveground carbon stocks in Theobroma cacao
agroforestry systems: implications for REDD+ implementation in a West African
cacao landscape.
AB - BACKGROUND: The promotion of cacao agroforestry is one of the ways of
diversifying farmer income and creating incentives through their inclusion in
REDD+ interventions. We estimated the aboveground carbon stocks in cacao and
shade trees, determined the floristic diversity of shade trees and explored the
possibility of implementing REDD+ interventions in cacao landscapes. Using
replicated multi-site transect approach, data were collected from nine 1-ha plots
established on 5 km long transects in ten cacao growing districts in Ghana West
Africa. Biomass of cacao and shade trees was determined using allometric
equations. RESULTS: One thousand four hundred and one (1401) shade trees
comprising 109 species from 33 families were recorded. Total number of species
ranged from 34 to 49. Newbouldia laevis (Bignoniacea) was the most frequently
occurring specie and constituted 43.2 % of all shade trees. The most predominant
families were Sterculiaceae and Moraceae (10 species each), followed by Meliaceae
and Mimosaceae (8 species each) and Caesalpiniacaea (6 species). Shannon
diversity indices (H', Hmax and J') and species richness were low compared to
other similar studies. Shade tree densities ranged from 16.2 +/- 3.0 to 22.8 +/-
1.7 stems ha-1 and differed significantly between sites. Carbon stocks of shade
trees differed between sites but were similar in cacao trees. The average C stock
in cacao trees was 7.45 +/- 0.41 Mg C ha-1 compared with 8.32 +/- 1.15 Mg C ha-1
in the shade trees. CONCLUSIONS: Cacao landscapes in Ghana have the potential of
contributing to forest carbon stocks enhancement by increasing the stocking
density of shade trees to recommended levels.
PMID- 27617027
TI - Chi-Ju-Di-Huang-Wan protects rats against retinal ischemia by downregulating
matrix metalloproteinase-9 and inhibiting p38 mitogen-activated protein kinase.
AB - BACKGROUND: Retinal ischemia is a retinal disorder related to retinal vascular
occlusion, glaucoma, diabetic retinopathy and age-related macular degeneration.
The study aimed to evaluate the protective effects and underlying mechanisms of
Chi-Ju-Di-Huang-Wan (CJDHW) against retinal ischemia in rats. METHODS: High
intraocular pressure (HIOP)-induced retinal ischemia was established in Wistar
rats by raising their intraocular pressure to 120 mmHg for 60 min with in an eye
whose anterior chamber was cannulated with a 30-guage needle adapted to a normal
saline bottle through an intravenous line. This ischemic insult was followed by 1
or 7 days of reperfusion. The effects of CJDHW were studied by (i)
electroretinogram (ERG); (ii) real-time polymerase chain reaction to determine
the retinal mRNA levels of Thy-1 and matrix metalloproteinase-9 (MMP-9); (iii)
Western blot analysis to determine the retinal protein levels of B cell lymphoma
2 (Bcl-2), heme oxygenase-1 (HO-1), phosphorylated-p38 mitogen-activated protein
kinase (P-p38 MAPK) and MMP-9; (iv) hematoxylin and eosin (HE) staining; (v)
fluorogold retrograde labeling; and (vi) terminal deoxynucleotidyl-transferase
(TdT)-mediated dUTP nick end-labeling (TUNEL) apoptosis assay. Moreover, after
fixation with 4 % paraformaldehyde and 30 % sucrose, the isolated retinas were
sectioned and immunolabeled with goat anti-choline acetyltransferase (ChAT)
polyclonal antibody, mouse anti-vimentin monoclonal antibody and rabbit anti
glial fibrillary acidic protein (GFAP) polyclonal antibody. The retinal sections
were then incubated with rhodamine-conjugated rabbit anti-goat antibody,
fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse IgG or FITC
conjugated goat anti-rabbit IgG. A daily oral intake of 3 mL of water (vehicle;
Group 2) or CJDHW (2.8 or 4.2 g/kg/day; CJDHW2.8 or CJDHW4.2; Group 3 or 4) was
given for 7 consecutive days either before (preischemic drug administration) or
after HIOP-induced retinal ischemic injury (postischemic drug administration). In
Group 5, an intravitreal injection of 4 MUL of 0.5 mM SB203580 (p38 MAPK
inhibitor) was performed on the ischemic eye 15 min before retinal ischemia. The
control rats received a sham procedure (Group 1) where the saline reservoir was
not raised. RESULTS: The ischemia-induced changes (Group 2) were significantly
modulated by pretreating the rats with 4.2 g/kg/day of CJDHW (Group 4; ERG: P <
0.001 on I/R day 7; HE stain: P < 0.001 on I/R day 7; TUNEL: P = 0.05 on I/R day
7; retrograde labeling: P = 0.007 on I/R day 7; Thy-1 mRNA: P = 0.02; MMP-9 mRNA:
P < 0.001; Bcl-2 protein: P = 0.02; HO-1 protein: P = 0.03; P-p38 MAPK protein: P
< 0.001; MMP-9 protein: P = 0.02). These modulations included the following
features (Group 2 vs. 4), increased ERG b-wave amplitudes (0.38 +/- 0.04 vs. 0.81
+/- 0.03), increased inner retinal thickness (45.08 +/- 2.85 vs. 67.98 +/- 5.48
MUm), increased ChAT immunolabeling, decreased vimentin/GFAP immunoreactivity,
less numerous apoptotic cells in the ganglion cell layer (1.40 +/- 0.55 vs. 0.60
+/- 0.55), and more numerous retinal ganglion cells (887.73 +/- 158.18 vs.
1389.02 +/- 53.20). Moreover, increased Thy-1 (0.31 +/- 0.15 vs. 0.78 +/- 0.32)
and decreased MMP-9 mRNA levels were found (4.44 +/- 0.84 vs. 1.13 +/- 0.34),
respectively. Furthermore, the Bcl-2 protein level (0.78 +/- 0.08 vs. 1.80 +/-
0.34) was increased while the HO-1 (0.99 +/- 0.20 vs. 4.15 +/- 2.08), P-p38 MAPK
(1.12 +/- 0.18 vs. 0.57 +/- 0.18) and MMP-9 levels were decreased (0.70 +/- 0.23
vs. 0.39 +/- 0.10). The ischemia-associated increases in P-p38 and MMP-9 protein
levels were also attenuated by 0.5 mM SB203580 (P-p38 MAPK: 1.12 +/- 0.18 vs.
0.18 +/- 0.07, P < 0.001; MMP-9: 0.70 +/- 0.23 vs. 0.21 +/- 0.07, P = 0.002).
This was also the case to the MMP_enzyme activity (Group 2 vs. 4: 5.03 +/- 1.57
vs. 1.59 +/- 0.47, P = 0.002; Group 2 vs. 5: 5.03 +/- 1.57 vs. 1.35 +/- 0.41, P =
0.001). CONCLUSION: Treatment of the rats suffering from retinal ischemia with
CJDHW inhibited apoptosis, increased antioxidative activity, downregulated MMP-9
and inhibited p38 MAPK.
PMID- 27617026
TI - 3D Printed Bionic Nanodevices.
AB - The ability to three-dimensionally interweave biological and functional materials
could enable the creation of bionic devices possessing unique and compelling
geometries, properties, and functionalities. Indeed, interfacing high performance
active devices with biology could impact a variety of fields, including
regenerative bioelectronic medicines, smart prosthetics, medical robotics, and
human-machine interfaces. Biology, from the molecular scale of DNA and proteins,
to the macroscopic scale of tissues and organs, is three-dimensional, often soft
and stretchable, and temperature sensitive. This renders most biological
platforms incompatible with the fabrication and materials processing methods that
have been developed and optimized for functional electronics, which are typically
planar, rigid and brittle. A number of strategies have been developed to overcome
these dichotomies. One particularly novel approach is the use of extrusion-based
multi-material 3D printing, which is an additive manufacturing technology that
offers a freeform fabrication strategy. This approach addresses the dichotomies
presented above by (1) using 3D printing and imaging for customized,
hierarchical, and interwoven device architectures; (2) employing nanotechnology
as an enabling route for introducing high performance materials, with the
potential for exhibiting properties not found in the bulk; and (3) 3D printing a
range of soft and nanoscale materials to enable the integration of a diverse
palette of high quality functional nanomaterials with biology. Further, 3D
printing is a multi-scale platform, allowing for the incorporation of functional
nanoscale inks, the printing of microscale features, and ultimately the creation
of macroscale devices. This blending of 3D printing, novel nanomaterial
properties, and 'living' platforms may enable next-generation bionic systems. In
this review, we highlight this synergistic integration of the unique properties
of nanomaterials with the versatility of extrusion-based 3D printing technologies
to interweave nanomaterials and fabricate novel bionic devices.
PMID- 27617030
TI - Beyond Cognition: Reading Motivation and Reading Comprehension.
AB - The authors review research on children's reading motivation and its relation to
their reading comprehension. They begin by discussing work on the development of
school motivation in general and reading motivation in particular, reviewing work
showing that many children's reading motivation declines over the school years.
Girls tend to have more positive motivation for reading than do boys, and there
are ethnic differences in children's reading motivation. Over the last 15 years
researchers have identified in both laboratory and classroom-based research
instructional practices that positively impact students' reading motivation and
ultimately their reading comprehension. There is a strong need for researchers to
build on this work and develop and study in different age groups of children
effective classroom-based reading motivation instructional programs for a variety
of narrative and informational materials.
PMID- 27617029
TI - Performance of non-parametric algorithms for spatial mapping of tropical forest
structure.
AB - BACKGROUND: Mapping tropical forest structure is a critical requirement for
accurate estimation of emissions and removals from land use activities. With the
availability of a wide range of remote sensing imagery of vegetation
characteristics from space, development of finer resolution and more accurate
maps has advanced in recent years. However, the mapping accuracy relies heavily
on the quality of input layers, the algorithm chosen, and the size and quality of
inventory samples for calibration and validation. RESULTS: By using airborne
lidar data as the "truth" and focusing on the mean canopy height (MCH) as a key
structural parameter, we test two commonly-used non-parametric techniques of
maximum entropy (ME) and random forest (RF) for developing maps over a study site
in Central Gabon. Results of mapping show that both approaches have improved
accuracy with more input layers in mapping canopy height at 100 m (1-ha) pixels.
The bias-corrected spatial models further improve estimates for small and large
trees across the tails of height distributions with a trade-off in increasing
overall mean squared error that can be readily compensated by increasing the
sample size. CONCLUSIONS: A significant improvement in tropical forest mapping
can be achieved by weighting the number of inventory samples against the choice
of image layers and the non-parametric algorithms. Without future satellite
observations with better sensitivity to forest biomass, the maps based on
existing data will remain slightly biased towards the mean of the distribution
and under and over estimating the upper and lower tails of the distribution.
PMID- 27617031
TI - Factors contributing to the psychological well-being for Hong Kong Chinese
children from low-income families: a qualitative study.
AB - BACKGROUND: Despite compelling evidence demonstrating the negative impact of
poverty and income disparity on children's psychological well-being, there has
been a lack of qualitative information which addresses its contributing factors.
This study aimed to shed light on this area by comparing the experiences toward
daily life between children living in low- and high-income families. METHODS: A
qualitative study using a phenomenological approach was conducted from May 2012
to January 2013. A random sample of 42 children aged 10-13, with 25 from low- and
17 from high-income families were asked to voluntarily response to a demographic
sheet and undergo individual semi-structured interviews which lasted about 25-30
min. Content analysis was used to analyze the data. Approval for the study was
obtained from the Institutional Review Board of the University of Hong
Kong/Hospital Authority Hong Kong West Cluster (reference UW 12-237). RESULTS:
The findings of this study revealed that the living environment, physical health,
social life and ability to function at school of children from low-income
families are severely impaired. CONCLUSIONS: It fills a gap in the literature by
showing how poverty and income disparity affect the daily lives of children from
low-income families on different levels. Also, adopting a sedentary lifestyle and
unhealthy eating habits are possible factors mediating the effects of poverty and
income disparity on the psychological well-being of children from low-income
families. It is vital for healthcare professionals going beyond their normal
roles to give advice on healthy lifestyles and behaviors by building
multidisciplinary partnerships with schools and the community. Additionally,
healthcare professionals should also target on these two possible factors to
develop and implement appropriate interventions for promoting the psychological
well-being among children living in poverty. Trial registration NCT02877719. 19
August 2016 retrospectively registered.
PMID- 27617032
TI - Affective Dynamics in Psychopathology.
AB - We discuss three varieties of affective dynamics (affective instability,
emotional inertia, and emotional differentiation). In each case, we suggest how
these affective dynamics should be operationalized and measured in daily life
using time-intensive methods, like ecological momentary assessment or ambulatory
assessment, and recommend time-sensitive analyses that take into account not only
the variability but also the temporal dependency of reports. Studies that explore
how these affective dynamics are associated with psychological disorders and
symptoms are reviewed, and we emphasize that these affective processes are within
a nexus of other components of emotion regulation.
PMID- 27617033
TI - Comment: Acquiring metaphors.
AB - Lakoff (current issue) describes an account of conceptual representation based in
part on metaphor. Though promising, this account faces several challenges with
respect to learning and development.
PMID- 27617036
TI - Socio-economic inequality in childhood and beyond: an overview of challenges and
findings from comparative analyses of cohort studies.
AB - The growing number of countries with large child cohort studies offers an
unprecedented opportunity for comparative research. A topic of central interest
in my research is, to what extent the sizable gaps in development that exist
between children from different socioeconomic status (SES) groups in the US are
also present in other countries, and to what extent the mechanisms explaining
these gaps are similar or different across countries. This overview draws on the
results of comparative analyses of birth cohort study data collected in
Australia, Canada, the United Kingdom, and the United States, to illustrate the
challenges that arise in carrying out this kind of research and the way these
challenges were met - in particular those having to do with data access and
comparability, and those having to do with causal inference. I conclude that this
type of research also offers great promise as shown by findings on SES gaps in
child development in the four countries.
PMID- 27617034
TI - Biomass traits and candidate genes for bioenergy revealed through association
genetics in coppiced European Populus nigra (L.).
AB - BACKGROUND: Second generation (2G) bioenergy from lignocellulosic feedstocks has
the potential to develop as a sustainable source of renewable energy; however,
significant hurdles still remain for large-scale commercialisation. Populus is
considered as a promising 2G feedstock and understanding the genetic basis of
biomass yield and feedstock quality are a research priority in this model tree
species. RESULTS: We report the first coppiced biomass study for 714 members of a
wide population of European black poplar (Populus nigra L.), a native European
tree, selected from 20 river populations ranging in latitude and longitude
between 40.5 and 52.1 degrees N and 1.0 and 16.4 degrees E, respectively. When
grown at a single site in southern UK, significant Site of Origin (SO) effects
were seen for 14 of the 15 directly measured or derived traits including biomass
yield, leaf area and stomatal index. There was significant correlation (p <
0.001) between biomass yield traits over 3 years of harvest which identified leaf
size and cell production as strong predictors of biomass yield. A 12 K Illumina
genotyping array (constructed from 10,331 SNPs in 14 QTL regions and 4648 genes)
highlighted significant population genetic structure with pairwise FST showing
strong differentiation (p < 0.001) between the Spanish and Italian
subpopulations. Robust associations reaching genome-wide significance are
reported for main stem height and cell number per leaf; two traits tightly linked
to biomass yield. These genotyping and phenotypic data were also used to show the
presence of significant isolation by distance (IBD) and isolation by adaption
(IBA) within this population. CONCLUSIONS: The three associations identified
reaching genome-wide significance at p < 0.05 include a transcription factor; a
putative stress response gene and a gene of unknown function. None of them have
been previously linked to bioenergy yield; were shown to be differentially
expressed in a panel of three selected genotypes from the collection and
represent exciting, novel candidates for further study in a bioenergy tree native
to Europe and Euro-Asia. A further 26 markers (22 genes) were found to reach
putative significance and are also of interest for biomass yield, leaf area,
epidermal cell expansion and stomatal patterning. This research on European P.
nigra provides an important foundation for the development of commercial native
trees for bioenergy and for advanced, molecular breeding in these species.
PMID- 27617037
TI - Understanding and Addressing Vulnerability Following the 2010 Haiti Earthquake:
Applying a Feminist Lens to Examine Perspectives of Haitian and Expatriate Health
Care Providers and Decision-Makers.
AB - Vulnerability is a central concept in humanitarian aid. Discussions of
vulnerability in disaster response literature and guidelines for humanitarian aid
range from considerations of a universal human vulnerability, to more nuanced
examinations of how particular characteristics render individuals more or less at
risk. Despite its frequent use, there is a lack of clarity about how
vulnerability is conceptualized and how it informs operational priorities in
humanitarian assistance. Guided by interpretive description methodology, we draw
on the feminist taxonomy of vulnerability presented by Mackenzie, Rogers and
Dodds (2014) to examine perspectives of 24 expatriate and Haitian decision-makers
and health professionals interviewed between May 2012 and March 2013. The
analysis explores concepts of vulnerability and equity in relation to the
humanitarian response following the 2010 earthquake in Haiti. Participants'
conceptualizations of vulnerability included consideration for inherent
vulnerabilities related to individual characteristics (e.g. being a woman or
disabled) and situational vulnerabilities related to particular circumstances
such as having less access to health care resources or basic necessities.
Participants recognized that vulnerabilities could be exacerbated by socio
political structures but felt ill-equipped to address these. The use of the
taxonomy and a set of questions inspired by Hurst's (2008) approach to
identifying and reducing vulnerability can guide the analysis of varied sources
of vulnerability and open discussions about how and by whom vulnerabilities
should be addressed in humanitarian responses. More research is required to
inform how humanitarian responders could balance addressing acute vulnerability
with consideration of systemic and pre-existing circumstances that underlie much
of the vulnerability experienced following an acute disaster.
PMID- 27617035
TI - Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and
Set1a and regulates H3K4 methylation at promoters and enhancers.
AB - BACKGROUND: Pax6 is a key regulator of the entire cascade of ocular lens
formation through specific binding to promoters and enhancers of batteries of
target genes. The promoters and enhancers communicate with each other through DNA
looping mediated by multiple protein-DNA and protein-protein interactions and are
marked by specific combinations of histone posttranslational modifications
(PTMs). Enhancers are distinguished from bulk chromatin by specific modifications
of core histone H3, including H3K4me1 and H3K27ac, while promoters show increased
H3K4me3 PTM. Previous studies have shown the presence of Pax6 in as much as 1/8
of lens-specific enhancers but a much smaller fraction of tissue-specific
promoters. Although Pax6 is known to interact with EP300/p300 histone
acetyltransferase responsible for generation of H3K27ac, a potential link between
Pax6 and histone H3K4 methylation remains to be established. RESULTS: Here we
show that Pax6 co-purifies with H3K4 methyltransferase activity in lens cell
nuclear extracts. Proteomic studies show that Pax6 immunoprecipitates with Set1a,
Mll1, and Mll2 enzymes, and their associated proteins, i.e., Wdr5, Rbbp5, Ash2l,
and Dpy30. ChIP-seq studies using chromatin prepared from mouse lens and cultured
lens cells demonstrate that Pax6-bound regions are mostly enriched with H3K4me2
and H3K4me1 in enhancers and promoters, though H3K4me3 marks only Pax6-containing
promoters. The shRNA-mediated knockdown of Pax6 revealed down-regulation of a set
of direct target genes, including Cap2, Farp1, Pax6, Plekha1, Prox1, Tshz2, and
Zfp536. Pax6 knockdown was accompanied by reduced H3K4me1 at enhancers and
H3K4me3 at promoters, with little or no changes of the H3K4me2 modifications.
These changes were prominent in Plekha1, a gene regulated by Pax6 in both lens
and retinal pigmented epithelium. CONCLUSIONS: Our study supports a general model
of Pax6-mediated recruitment of histone methyltransferases Mll1 and Mll2 to lens
chromatin, especially at distal enhancers. Genome-wide data in lens show that
Pax6 binding correlates with H3K4me2, consistent with the idea that H3K4me2 PTMs
correlate with the binding of transcription factors. Importantly, partial
reduction of Pax6 induces prominent changes in local H3K4me1 and H3K4me3
modification. Together, these data open the field to mechanistic studies of Pax6,
Mll1, Mll2, and H3K4me1/2/3 dynamics at distal enhancers and promoters of
developmentally controlled genes.
PMID- 27617038
TI - 3D-printed Microfluidic Devices: Fabrication, Advantages and Limitations-a Mini
Review.
AB - A mini-review with 79 references. In this review, the most recent trends in 3D
printed microfluidic devices are discussed. In addition, a focus is given to the
fabrication aspects of these devices, with the supplemental information
containing detailed instructions for designing a variety of structures including:
a microfluidic channel, threads to accommodate commercial fluidic fittings, a
flow splitter; a well plate, a mold for PDMS channel casting; and how to combine
multiple designs into a single device. The advantages and limitations of 3D
printed microfluidic devices are thoroughly discussed, as are some future
directions for the field.
PMID- 27617039
TI - Parent and Teacher Concordance on the Social Responsiveness Scale for Children
with Autism.
AB - There are inconsistent findings regarding parent and teacher agreement on
behavioral ratings of their children with autism. One possible reason for this
inconsistency is that studies have not taken autism severity into account. This
study examined parent and teacher concordance of social behavior based on symptom
severity for children with autism. Participants were 123 parent-teacher dyads who
completed the Social Responsiveness Scale. Symptom severity was assessed using
the Autism Diagnostic Observation Schedule (ADOS). Results indicated that parent
and teacher ratings were statistically significantly correlated at the beginning
and end of the academic year, but only for severely affected children. Teacher
report of social deficits was correlated with symptom severity as measured by the
ADOS; parent report was not. These findings have implications for improving
assessment procedures and parent-teacher collaboration.
PMID- 27617041
TI - Subgroup-Based Adaptive (SUBA) Designs for Multi-Arm Biomarker Trials.
AB - Targeted therapies based on biomarker profiling are becoming a mainstream
direction of cancer research and treatment. Depending on the expression of
specific prognostic biomarkers, targeted therapies assign different cancer drugs
to subgroups of patients even if they are diagnosed with the same type of cancer
by traditional means, such as tumor location. For example, Herceptin is only
indicated for the subgroup of patients with HER2+ breast cancer, but not other
types of breast cancer. However, subgroups like HER2+ breast cancer with
effective targeted therapies are rare and most cancer drugs are still being
applied to large patient populations that include many patients who might not
respond or benefit. Also, the response to targeted agents in humans is usually
unpredictable. To address these issues, we propose SUBA, subgroup-based adaptive
designs that simultaneously search for prognostic subgroups and allocate patients
adaptively to the best subgroup-specific treatments throughout the course of the
trial. The main features of SUBA include the continuous reclassification of
patient subgroups based on a random partition model and the adaptive allocation
of patients to the best treatment arm based on posterior predictive
probabilities. We compare the SUBA design with three alternative designs
including equal randomization, outcome-adaptive randomization and a design based
on a probit regression. In simulation studies we find that SUBA compares
favorably against the alternatives.
PMID- 27617040
TI - Bayesian Two-stage Biomarker-based Adaptive Design for Targeted Therapy
Development.
AB - We propose a Bayesian two-stage biomarker-based adaptive randomization (AR)
design for the development of targeted agents. The design has three main goals:
(1) to test the treatment efficacy, (2) to identify prognostic and predictive
markers for the targeted agents, and (3) to provide better treatment for patients
enrolled in the trial. To treat patients better, both stages are guided by the
Bayesian AR based on the individual patient's biomarker profiles. The AR in the
first stage is based on a known marker. A Go/No-Go decision can be made in the
first stage by testing the overall treatment effects. If a Go decision is made at
the end of the first stage, a two-step Bayesian lasso strategy will be
implemented to select additional prognostic or predictive biomarkers to refine
the AR in the second stage. We use simulations to demonstrate the good operating
characteristics of the design, including the control of per-comparison type I and
type II errors, high probability in selecting important markers, and treating
more patients with more effective treatments. Bayesian adaptive designs allow for
continuous learning. The designs are particularly suitable for the development of
multiple targeted agents in the quest of personalized medicine. By estimating
treatment effects and identifying relevant biomarkers, the information acquired
from the interim data can be used to guide the choice of treatment for each
individual patient enrolled in the trial in real time to achieve a better
outcome. The design is being implemented in the BATTLE-2 trial in lung cancer at
the MD Anderson Cancer Center.
PMID- 27617042
TI - Examination of Life Satisfaction, Child Maltreatment Potential and Substance Use
in Mothers Referred for Treatment by Child Protective Services for Child Neglect
and Substance Abuse: Implications for Intervention Planning.
AB - There is evidence to suggest mothers who are served by child protective service
agencies are relatively dissatisfied in their lives, leading some investigators
to conclude life dissatisfaction may be associated with child maltreatment. To
assist in better understanding this relationship the Life Satisfaction Scale for
Caregivers (LSSC) was psychometrically developed in a sample of 72 mothers who
were referred for behavioral treatment for child neglect and substance abuse by
caseworkers from a local child protective service agency. The LSSC was developed
to assess mothers' happiness in nine domains (family, friendships,
employment/work, spirituality/religion, safety, sex life/dating, ability to avoid
drugs, ability to avoid alcohol, control over one's own life). Results indicated
two factors that appeared to be relevant to Social Satisfaction and Safety and
Control Satisfaction. Higher satisfaction scores on both of these scales were
negatively associated with child maltreatment potential and substance use at
baseline (i.e., positive urinalysis test). Mothers who exposed their children to
substances in utero or in infancy (a distinct type of child neglect) were found
to report higher satisfaction scores on the LSSC than other types of child
neglect. Hispanic-American, African-American, and Caucasian women reported
similar levels of life satisfaction. Application of the LSSC as a non
stigmatizing, wellness-focused instrument is discussed within the context of
intervention planning.
PMID- 27617043
TI - Ecological Factors of Being Bullied Among Adolescents: a Classification and
Regression Tree Approach.
AB - Being bullied is a well-recognized trauma for adolescents. Bullying can best be
understood through an ecological framework since bullying or being bullied
involves risk factors at multiple contextual levels. The purpose of the study was
to identify the risk and protective factors that best differentiate groups along
with the outcome variable of interest (being bullied) using Classification and
Regression Tree (CART) analysis. The study used the Health Behavior in School
Aged Children (HBSC) data collected from a nationally representative sample of
students in grades six through ten during the 2005-2006 school years. This study
identified that for adolescents 12 and younger, lower parental support is a
critical risk factor associated with bullying and among those 13 to 14 with lower
parent support, adolescent with higher academic pressure reported experiencing
more bullying. For the older group of adolescents (aged 15 and older), school
related factors were identified to increase the risk level of being bullied.
There was a critical age (15 years old) for implementing victimization
interventions to reduce the damage from being bullied. Service providers working
with adolescents aged 14 and less should focus more on family-oriented
intervention and those working with adolescents aged 15 and more should offer
peer- or school-related interventions.
PMID- 27617045
TI - Voices and Thoughts in Psychosis: An Introduction.
AB - In this introduction we present the orthodox account of auditory verbal
hallucinations (AVHs), a number of worries for this account, and some potential
responses open to its proponents. With some problems still remaining, we then
introduce the problems presented by the phenomenon of thought insertion, in
particular the question of how different it is supposed to be from AVHs. We then
mention two ways in which theorists have adopted different approaches to voices
and thoughts in psychosis, and then present the motivation and composition of
this special issue.
PMID- 27617044
TI - Clustering Home Activity Distributions for Automatic Detection of Mild Cognitive
Impairment in Older Adults.
AB - The public health implications of growing numbers of older adults at risk for
dementia places pressure on identifying dementia at its earliest stages so as to
develop proactive management plans. The prodromal dementia phase commonly
identified as mild cognitive impairment is an important target for this early
detection of impending dementia amenable to treatment. In this paper, we propose
a method for home-based automatic detection of mild cognitive impairment in older
adults through continuous monitoring via unobtrusive sensing technologies. Our
method is composed of two main stages: a training stage and a test stage. For
training, room activity distributions are estimated for each subject using a time
frame of omega weeks, and then affinity propagation is employed to cluster the
activity distributions and to extract exemplars to represent the different
emerging clusters. For testing, room activity distributions belonging to a test
subject with unknown cognitive status are compared to the extracted exemplars and
get assigned the labels of the exemplars that result in the smallest normalized
Kullbak-Leibler divergence. The labels of the activity distributions are then
used to determine the cognitive status of the test subject. Using the sensor and
clinical data pertaining to 85 homes with single occupants, we were able to
automatically detect mild cognitive impairment in older adults with an F0.5 score
of 0.856. Also, we were able to detect the non-amnestic sub-type of mild
cognitive impairment in older adults with an F0.5 score of 0.958.
PMID- 27617047
TI - Visualization of the Spinal Artery by CT During Embolization for Pulmonary Artery
Pseudoaneurysm.
AB - BACKGROUND: Spinal artery ischemia is a rare but serious complication of
embolization for treatment of hemoptysis. When the spinal artery is visualized at
angiography, embolization should not be performed. However, it has been reported
that spinal artery feeders are not visible on angiography in patients with
developing spinal infarction. CASE REPORT: A 70-year-old man with a history of
pulmonary aspergillosis had hemoptysis and underwent contrast-enhanced CT,
revealing a pulmonary artery pseudoaneurysm (PAP) in the left upper lobe.
Systemic angiography from the fifth left intercostal artery showed the PAP at the
distal site, but the access route to the PAP was very tortuous and long. Although
the spinal branch could not be observed with that angiography, CT during
angiography was performed, and it visualized the posterior spinal artery
obviously. Thus, the artery distal and proximal to the PAP was then successfully
coil-embolized from the pulmonary artery. CONCLUSIONS: CT during angiography may
be useful to confirm the presence of the spinal artery for treatment of
hemoptysis by embolization.
PMID- 27617048
TI - Evaluation of Doses and Image Quality in Mammography with Screen-Film, CR, and DR
Detectors - Application of the ACR Phantom.
AB - BACKGROUND: Different methods of image quality evaluation are routinely used for
analogue and digital mammography systems in Poland. In the present study, image
quality for several screen-film (SF), computed radiography (CR), and fully
digital (DR) mammography systems was compared directly with the use of the ACR
mammography accreditation phantom. MATERIAL/METHODS: Image quality and mean
glandular doses were measured and compared for 47 mammography systems in the
Mazovia Voivodeship in Poland, including 26 SF systems, 12 CR systems, and 9 DR
systems. The mean glandular dose for the breast simulated by 4.5 cm of PMMA was
calculated with methods described in the "European guidelines for quality
assurance in breast cancer screening and diagnosis". Visibility of the structures
in the image (fibers, microcalcifications, and masses) was evaluated with the
mammographic accreditation ACR phantom. RESULTS: Image quality for DR systems was
significantly higher than for SF and CR systems. Several SF systems failed to
pass the image quality tests because of artifacts. The doses were within
acceptable limits for all of the systems, but the doses for the CR systems were
significantly higher than for the SF and DR systems. CONCLUSIONS: The best image
quality, at a reasonably low dose, was observed for the DR systems. The CR
systems are capable of obtaining the same image quality as the SF systems, but
only at a significantly higher dose. The ACR phantom can be routinely used to
evaluate image quality for all types of mammographic systems.
PMID- 27617046
TI - A Neuropsychological Approach to Auditory Verbal Hallucinations and Thought
Insertion - Grounded in Normal Voice Perception.
AB - A neuropsychological perspective on auditory verbal hallucinations (AVH) links
key phenomenological features of the experience, such as voice location and
identity, to functionally separable pathways in normal human audition. Although
this auditory processing stream (APS) framework has proven valuable for
integrating research on phenomenology with cognitive and neural accounts of
hallucinatory experiences, it has not yet been applied to other symptoms presumed
to be closely related to AVH - such as thought insertion (TI). In this paper, I
propose that an APS framework offers a useful way of thinking about the
experience of TI as well as AVH, providing a common conceptual framework for
both. I argue that previous self-monitoring theories struggle to account for both
the differences and similarities in the characteristic features of AVH and TI,
which can be readily accommodated within an APS framework. Furthermore, the APS
framework can be integrated with predictive processing accounts of psychotic
symptoms; makes predictions about potential sites of prediction error signals;
and may offer a template for understanding a range of other symptoms beyond AVH
and TI.
PMID- 27617049
TI - Giant Atretic Occipital Lipoencephalocele in an Adult with Bony Outgrowth.
AB - BACKGROUND: We present unique case of a giant extracranial atretic occipital
lipoencephalocele in an adult patient with new bone formation within it which was
not associated with any developmental malformation of brain. Resection of the
lipoencephalocele was performed for esthetic reasons. CASE REPORT: 18 year old
female patient presented to the surgery OPD with complains of a large mass in the
occipital region present since birth. It was of size of a betel nut at the time
of birth and gradually increased in size over a long period of time. It was
painless and not associated with any other constitutional symptoms. On
examination the rounded fluctuant mass was present in the midline in occipital
region covered with alopecic skin with dimpling in the overlying skin. On MRI
there was mass showing both T1 and T2 hyperintense signal area suggestive of fat
component. Herniation of meninges and atretic brain parenchyma was also seen
through a defect in the occipital bone in the midline. There was a Y shaped bony
outgrowth seen arising from occipital bone into the mass which was quite unusual
in association with an atretic lipoencephalocele. CONCLUSIONS: A large
lipoencephalocele with bony outgrowth in an adult patient is a rare presentation
of atreic occipital encephalocele.
PMID- 27617051
TI - Statistical properties of convex clustering.
AB - In this manuscript, we study the statistical properties of convex clustering. We
establish that convex clustering is closely related to single linkage
hierarchical clustering and k-means clustering. In addition, we derive the range
of the tuning parameter for convex clustering that yields a non-trivial solution.
We also provide an unbiased estimator of the degrees of freedom, and provide a
finite sample bound for the prediction error for convex clustering. We compare
convex clustering to some traditional clustering methods in simulation studies.
PMID- 27617050
TI - Chronic Neglect and Services Without Borders: A Guiding Model for Social Service
Enhancement to Address the Needs of Parents With Intellectual Disabilities.
AB - Child neglect has negative effects throughout the lifespan. Although an argument
for a link between intellectual disabilities and neglectful parenting can be
made, this paper argues for a more fine grained view of the cognitive problems
that underlie child neglect perpetration and provides evidence for a social
information processing model of etiology. Based on this model and what is known
about the efficacy of behaviorally-based interventions, implications for
enhancements to the social service system to adapt to the needs of parents with
intellectual disabilities are presented. The areas covered include improvements
to screening and assessment of parents; provision of adapted services; and
changes in selection processes and training of staff. Future directions for
integrating social information processing elements into interventions are
discussed with examples from empirically tested prevention programs.
PMID- 27617052
TI - An Inexact Newton-Krylov Algorithm for Constrained Diffeomorphic Image
Registration.
AB - We propose numerical algorithms for solving large deformation diffeomorphic image
registration problems. We formulate the nonrigid image registration problem as a
problem of optimal control. This leads to an infinite-dimensional partial
differential equation (PDE) constrained optimization problem. The PDE constraint
consists, in its simplest form, of a hyperbolic transport equation for the
evolution of the image intensity. The control variable is the velocity field.
Tikhonov regularization on the control ensures well-posedness. We consider
standard smoothness regularization based on H1- or H2-seminorms. We augment this
regularization scheme with a constraint on the divergence of the velocity field
(control variable) rendering the deformation incompressible (Stokes
regularization scheme) and thus ensuring that the determinant of the deformation
gradient is equal to one, up to the numerical error. We use a Fourier
pseudospectral discretization in space and a Chebyshev pseudospectral
discretization in time. The latter allows us to reduce the number of unknowns and
enables the time-adaptive inversion for nonstationary velocity fields. We use a
preconditioned, globalized, matrix-free, inexact Newton-Krylov method for
numerical optimization. A parameter continuation is designed to estimate an
optimal regularization parameter. Regularity is ensured by controlling the
geometric properties of the deformation field. Overall, we arrive at a black-box
solver that exploits computational tools that are precisely tailored for solving
the optimality system. We study spectral properties of the Hessian, grid
convergence, numerical accuracy, computational efficiency, and deformation
regularity of our scheme. We compare the designed Newton-Krylov methods with a
globalized Picard method (preconditioned gradient descent). We study the
influence of a varying number of unknowns in time. The reported results
demonstrate excellent numerical accuracy, guaranteed local deformation
regularity, and computational efficiency with an optional control on local mass
conservation. The Newton-Krylov methods clearly outperform the Picard method if
high accuracy of the inversion is required. Our method provides equally good
results for stationary and nonstationary velocity fields for two-image
registration problems.
PMID- 27617053
TI - Fournier's Gangrene and the Reconstructive Challenges for the Plastic Surgeon.
PMID- 27617054
TI - Electromagnetic and Thermal Simulations of Human Neurons for SAR Applications.
AB - The impact of the electromagnetic waves (EM) on human neurons (HN) has been under
investigation for decades, in efforts to understand the impact of cell phones
(radiation) on human health, or radiation absorption by HN for medical diagnosis
and treatment. Research issues including the wave frequency, power intensity,
reflections and scattering, and penetration depths are of important
considerations to be incorporated into the research study. In this study,
computer simulation for the EM exposure to HN was studied for the purpose of
determining the upper limits of the electric and magnetic field intensities,
power consumption, reflections and transmissions, and the change in temperature
resulting from the power absorption by human neurons. Both high frequency
structural simulators (HFSS) from ANSYS software, and COMSOL multi-physics were
used for the simulation of the EM transmissions and reflections, and the
temperature profile within the cells, respectively. For the temperature profile
estimation, the study considers an electrical source of 0.5 watt input power, 64
MHz. The EM simulation was looking into the uniformity of the fields within the
sample cells. The size of the waveguide was set to be appropriate for a small
animal model to be conducted in the future. The incident power was fully
transmitted throughout the waveguide, and less than 1% reflections were observed
from the simulation. The minimum reflected power near the sample under
investigation was found to be with negligible reflected field strengths. The
temperature profile resulting from the COMSOL simulation was found to be near
0.25 m degrees K, indicating no change in temperature on the neuro cells under
the EM exposure. The paper details the simulation results for the EM response
determined by HFSS, and temperature profile simulated by COMSOL.
PMID- 27617056
TI - An improved high-quality draft genome sequence of Carnobacterium inhibens subsp.
inhibens strain K1(T).
AB - Despite their ubiquity and their involvement in food spoilage, the genus
Carnobacterium remains rather sparsely characterized at the genome level.
Carnobacterium inhibens K1(T) is a member of the Carnobacteriaceae family within
the class Bacilli. This strain is a Gram-positive, rod-shaped bacterium isolated
from the intestine of an Atlantic salmon. The present study determined the genome
sequence and annotation of Carnobacterium inhibens K1(T). The genome comprised
2,748,608 bp with a G + C content of 34.85 %, which included 2621 protein-coding
genes and 116 RNA genes. The strain contained five contigs corresponding to
presumptive plasmids of sizes: 19,036; 24,250; 26,581; 65,272; and 65,904 bp.
PMID- 27617055
TI - Physician and Patient Barriers to Breast Cancer Preventive Therapy.
AB - The uptake of selective estrogen receptor modulators (SERMs) and aromatase
inhibitors (AIs) for the primary prevention of breast cancer is low, despite
their proven efficacy in several randomized clinical trials. This review
summarizes the latest data on physicians' and women's barriers to breast cancer
preventive therapy. Physicians' challenges include: identifying suitable
candidates for preventive therapy, inadequate training and confidence in risk
assessment and counselling, insufficient knowledge of risk-reducing medications,
and lack of time. High-risk women fear medication side effects, and they often
weigh experiences of others more heavily than statistical probabilities to guide
their decision-making. Despite decision aid interventions to help women make an
informed decision, acceptance of preventive therapy will remain low until:
risk/benefit profiles are more favorable, physicians are better educated and
skilled in having these discussions, and suitable biomarkers to monitor drug
efficacy and better clinical risk prediction models to assess true individual
risk are available.
PMID- 27617057
TI - Complete genome sequence of Desulfurivibrio alkaliphilus strain AHT2(T), a
haloalkaliphilic sulfidogen from Egyptian hypersaline alkaline lakes.
AB - Desulfurivibrio alkaliphilus strain AHT2(T) is a strictly anaerobic sulfidogenic
haloalkaliphile isolated from a composite sediment sample of eight hypersaline
alkaline lakes in the Wadi al Natrun valley in the Egyptian Libyan Desert. D.
alkaliphilus AHT2(T) is Gram-negative and belongs to the family Desulfobulbaceae
within the Deltaproteobacteria. Here we report its genome sequence, which
contains a 3.10 Mbp chromosome. D. alkaliphilus AHT2(T) is adapted to survive
under highly alkaline and moderately saline conditions and therefore, is relevant
to the biotechnology industry and life under extreme conditions. For these
reasons, D. alkaliphilus AHT2(T) was sequenced by the DOE Joint Genome Institute
as part of the Community Science Program.
PMID- 27617058
TI - Draft genome sequence of Thermoactinomyces sp. strain AS95 isolated from a Sebkha
in Thamelaht, Algeria.
AB - The members of the genus Thermoactinomyces are known for their protein
degradative capacities. Thermoactinomyces sp. strain AS95 is a Gram-positive
filamentous bacterium, isolated from moderately saline water in the Thamelaht
region of Algeria. This isolate is a thermophilic aerobic bacterium with the
capacity to produce extracellular proteolytic enzymes. This strain exhibits up to
99 % similarity with members of the genus Thermoactinomyces, based on 16S rRNA
gene sequence similarity. Here we report on the phenotypic features of
Thermoactinomyces sp. strain AS95 together with the draft genome sequence and its
annotation. The genome of this strain is 2,558,690 bp in length (one chromosome,
but no plasmid) with an average G + C content of 47.95 %, and contains 2550
protein-coding and 60 RNA genes together with 64 ORFs annotated as proteases.
PMID- 27617059
TI - Advances in biodiversity: metagenomics and the unveiling of biological dark
matter.
AB - BACKGROUND: Efforts to harmonize genomic data standards used by the biodiversity
and metagenomic research communities have shown that prokaryotic data cannot be
understood or represented in a traditional, classical biological context for
conceptual reasons, not technical ones. RESULTS: Biology, like physics, has a
fundamental duality-the classical macroscale eukaryotic realm vs. the quantum
microscale microbial realm-with the two realms differing profoundly, and counter
intuitively, from one another. Just as classical physics is emergent from and
cannot explain the microscale realm of quantum physics, so classical biology is
emergent from and cannot explain the microscale realm of prokaryotic life.
Classical biology describes the familiar, macroscale realm of multi-cellular
eukaryotic organisms, which constitute a highly derived and constrained
evolutionary subset of the biosphere, unrepresentative of the vast, mostly
unseen, microbial world of prokaryotic life that comprises at least half of the
planet's biomass and most of its genetic diversity. The two realms occupy
fundamentally different mega-niches: eukaryotes interact primarily mechanically
with the environment, prokaryotes primarily physiologically. Further, many
foundational tenets of classical biology simply do not apply to prokaryotic
biology. CONCLUSIONS: Classical genetics one held that genes, arranged on
chromosomes like beads on a string, were the fundamental units of mutation,
recombination, and heredity. Then, molecular analysis showed that there were no
fundamental units, no beads, no string. Similarly, classical biology asserts that
individual organisms and species are fundamental units of ecology, evolution, and
biodiversity, composing an evolutionary history of objectively real, lineage
defined groups in a single-rooted tree of life. Now, metagenomic tools are
forcing a recognition that there are no completely objective individuals, no
unique lineages, and no one true tree. The newly revealed biosphere of microbial
dark matter cannot be understood merely by extending the concepts and methods of
eukaryotic macrobiology. The unveiling of biological dark matter is allowing us
to see, for the first time, the diversity of the entire biosphere and, to
paraphrase Darwin, is providing a new view of life. Advancing and understanding
that view will require major revisions to some of the most fundamental concepts
and theories in biology.
PMID- 27617061
TI - Measurement Noninvariance of Safer Sex Self-Efficacy Between Heterosexual and
Sexual Minority Black Youth.
AB - OBJECTIVE: Black and lesbian, gay, bisexual, or questioning (LGBQ) youth in the
United States are disproportionately affected by HIV and other sexually
transmitted diseases (STDs). Although self-efficacy is strongly, positively
associated with safer sex behaviors, no studies have examined the validity of a
safer sex self-efficacy scale used by many federally funded HIV/STD prevention
programs. This study aims to test factor validity of the Sexual Self-Efficacy
Scale by using confirmatory factor analysis (CFA) to determine if scale validity
varies between heterosexual and LGBQ Black youth. METHOD: The study uses cross
sectional data collected through baseline surveys with 226 Black youth (15 to 24
years) enrolled in community-based HIV-prevention programs. Participants use a 4
point Likert-type scale to report their confidence in performing 6 healthy sexual
behaviors. CFAs are conducted on 2 factor structures of the scale. Using the best
fitting model, the scale is tested for measurement invariance between the 2
groups. RESULTS: A single-factor model with correlated errors of condom-specific
items fits the sample well and, when tested with the heterosexual group, the
model demonstrates good fit. However, when tested with the LGBQ group, the same
model yields poor fit, indicating factorial noninvariance between the groups.
CONCLUSIONS: The Sexual Self-Efficacy Scale does not perform equally well among
Black heterosexual and LGBQ youth. Study findings suggest additional research is
needed to inform development of measures for safer sex self-efficacy among Black
LGBQ youth to ensure validity of conceptual understanding and to accurately
assess effectiveness of HIV/STD prevention interventions among this population.
PMID- 27617060
TI - Complete genome sequence of the Antarctic Halorubrum lacusprofundi type strain
ACAM 34.
AB - Halorubrum lacusprofundi is an extreme halophile within the archaeal phylum
Euryarchaeota. The type strain ACAM 34 was isolated from Deep Lake, Antarctica.
H. lacusprofundi is of phylogenetic interest because it is distantly related to
the haloarchaea that have previously been sequenced. It is also of interest
because of its psychrotolerance. We report here the complete genome sequence of
H. lacusprofundi type strain ACAM 34 and its annotation. This genome is part of a
2006 Joint Genome Institute Community Sequencing Program project to sequence
genomes of diverse Archaea.
PMID- 27617062
TI - Extramedullary Relapse of Acute Myeloid and Lymphoid Leukemia in Children: A
Retrospective Analysis.
AB - BACKGROUND: Extramedullary relapse (EMR) is a recurrence of leukemia in sites
other than the bone marrow, and it exhibits a relatively rare presentation of
relapse of acute leukemia. However, EMR is an important cause of treatment
failure among patients with acute leukemia. Therefore, early detection of these
relapses may improve the prognosis. OBJECTIVES: To describe the disease-related
demographic and clinical features and radiologic findings for children diagnosed
with EMR in acute leukemia. PATIENTS AND METHODS: The study was based on 22
children (M: F = 14: 8; mean age 7.30 (2.1 - 15.7) years) with 8 acute myeloid
leukemia (AML) and 14 acute lymphoid leukemia (ALL) who had experienced an EMR.
Age, gender, clinical symptoms, initial extramedullary disease (EMD), French
American-British (FAB) morphology, cytogenetics, time to and site of EMR,
concurrent bone marrow relapse (BMR), radiologic findings, and outcomes were
evaluated. RESULTS: No definite relationship was found between initial EMD and
EMR. A predilection for AML to relapse in the central nervous system (CNS),
except for the CSF and bone, and for ALL to relapse in the CSF and kidney seemed
to occur. Patients with EMR had a significantly higher incidence of t(8: 21)
cytogenetics and FAB M2 and L1 morphologies. EMR accompanied with concurrent BMR
occurred in 31.8% of the patients, who exhibited a relatively grave clinical
course. Radiologic findings were nonspecific and had a great variety of structure
involved, including bulging enhancing mass in the CT scan, hypoechoic mass in the
US, and enhanced mass-like lesion in the MRI. CONCLUSIONS: Knowledge of the
potential sites of EMR, their risk factors, and their clinical and radiologic
features may be helpful in the early diagnosis of relapse and planning for
therapy.
PMID- 27617063
TI - Evaluation of Serum Adenosine Deaminase in Cystic Fibrosis Patients in an Iranian
Referral Hospital.
AB - BACKGROUND: Adenosine, a signaling nucleoside, is controlled in part by the
enzyme adenosine deaminase (ADA). There are rare reports on the role of adenosine
levels and ADA in cystic fibrosis (CF) patients. OBJECTIVES: The aim of this
study was to assess serum ADA in CF patients in order to find whether the
severity of lung disease in CF is related to significant changes of ADA or not.
PATIENTS AND METHODS: Venous blood serum ADA was measured in CF patients (3-15
years) and 49 healthy children (3-15 years) referred to Children's Medical
Center. Classification of respiratory and gastrointestinal disease severity in CF
patients as well as Body Mass Index (BMI) was performed. The results were
compared with values obtained from healthy children matched for age and gender.
RESULTS: This study included 49 children of both genders (20 females and 29
males) with CF (mean age: 6.36 +/- 2.22 years). Mean serum ADA in CF patients
group and control group was 9.38 +/- 2.72 and 16.04 +/- 1.27, respectively (P
value = 0.001). Mean serum ADA in CF patients with normal BMI was higher than in
patients with low BMI (P value = 0.002). CONCLUSIONS: In this study the lower
serum level of ADA was seen in CF patients compared to control group. The
clinical symptoms, especially respiratory symptoms, in CF patients might be
associated with reduction of serum ADA and rising serum adenosine; therefore,
further studies on the use of ADA enzyme therapy in CF patients are highly
recommended.
PMID- 27617066
TI - Bilineal Acute Leukemia Associated With Fanconi Syndrome: The First Case Report.
AB - Fanconi syndrome is a metabolic disorder involving dysfunction of the renal
proximal tubules, resulting in excessive urinary excretion of several
metabolites. Various factors may lead to Fanconi syndrome, as it may be a genetic
disease with primary or secondary etiologies, or may be acquired. In this study,
we report a unique case of Fanconi syndrome with development of a relatively rare
acute leukemia, a condition that has not been reported before. The case was an 8
year-old boy with familial occurrence of Fanconi syndrome, presenting with
pallor, asthenia, recurrent infections, growth failure, and a variety of
biochemical and hematological abnormalities. After physical examination,
radiographic studies, and comprehensive laboratory analyses, Fanconi syndrome
associated with bilineal acute leukemia, of myeloid and T-lymphoid lineages, was
diagnosed.
PMID- 27617065
TI - Follow-Up Results of Device Occlusion of Patent Ductus Arteriosus.
AB - BACKGROUND: Transcatheter patent ductus arteriosus (PDA) closure is an
established procedure. OBJECTIVES: The aim of the study was to assess midterm
follow up of the Nit-Occlud coil and the amplatzer ductal occluder (ADO) closure
of PDA. PATIENTS AND METHODS: In this cohort study, we collected the longitudinal
data of patients who underwent percutaneous closure using coil or ADO from
November 2005 to November 2013. A total of 404 patients with PDA closure by
devices were included during the study period. Coil occlusion was performed in
220 patients and 184 patients underwent catheterization using ADO. Follow-up
evaluations were performed with echocardiography at two weeks, two months, six
months, and during the study period (in average 4.8 +/- 3.8 years). RESULTS: The
patients' mean age was 24 months (range: 1 - 312). The catheterization was
successful in 393 (97.2%) patients and unsuccessful in 11 (2.7%). Immediate
complete occlusion was seen in 290 (73.7 %) patients. The occlusion rates at two
weeks, two months, six months, and during the study period were 73.7%, 84%,
93.6%, 98.7%, and 99.5%, respectively. Complications occurred in 23 (5.8%)
patients during or immediately after the catheterization, and device embolization
with 2.7% was the most common complication. Most complications occurred in a
patient with pulmonary hypertension who was less than one year old and was
undergoing the first year of experience with devices. CONCLUSIONS: Our findings
showed that transcatheter occlusion of the PDA is an effective and safe
intervention by coil or Amplatzer with excellent early and one-year outcomes.
Pulmonary hypertension, age of less than 12 months and experience of less than
one year may increase the complications of device closure.
PMID- 27617064
TI - A Systematic Review on the Prevalence of Overweight and Obesity, in Iranian
Children and Adolescents.
AB - CONTEXT: Obesity has now become a common health problem worldwide. To gain
insight into the epidemiology of the problem in Iran, we systematically reviewed
all available studies on the prevalence of overweight and obesity in the Iranian
pediatric population. EVIDENCE ACQUISITION: We systematically searched PubMed,
ISI, SCOPUS, as well as Iranmedex, Irandoc, and Scientific Information Database
(SID) databases.All studies on mean and standard deviation or percentile
categories of BMI, WC, WHR, or WHtR or prevalence of obesity/overweight in
Iranian child and adolescence, were performed from January 1990 to the end of
December 2013. Refining processes were conducted by two independent reviewers.
Quality assessment and data extraction followed based on validated form. As,
these data were heterogeneous, meta-analysis was not performed. RESULTS: From
3253 records, through three refining steps, 129 articles were found related to
our study. In Iran, national studies are limited and nearly there is no
comprehensive study for sub-national trends. Different age and sex groups had
large variations in the prevalence of obesity and overweight (from 1% up to 16.1%
and from 4.4% up to 42.3% respectively for obesity and overweight). CONCLUSIONS:
Related data are very scattered or limited to some specific subgroups in some
living areas. For comparing, aggregating, and imputing the information we need
more modern practical statistical methods.
PMID- 27617067
TI - Respiratory Burst Process in Diabetic Children.
AB - BACKGROUND: Increased rate of infections in diabetes mellitus (DM) is an accepted
fact. Pathophysiologically, several tasks of the immune system could be involved
including polymorphonuclear (PMN) functions. OBJECTIVES: The aim of this research
was to evaluate the respiratory burst process of PMNs that is an essential part
of phagocytosis, in children with DM. PATIENTS AND METHODS: Fifty two children
with insulin dependent diabetes and 29 non-diabetic children were enrolled in
this cross sectional study from 2010 to 2011. Nitroblue tetrazolium (NBT) test
was done on PMNs taken from their heparinized blood. The resultant data was
analyzed by SPSS version 16. P values were considered significant when it was
under 0.05. RESULTS: Mean NBTs were 72.1 +/- 15.84 and 94.68 +/- 5.31 in
diabetics and non-diabetics, respectively (P < 0.001). Using Pearson correlation,
there was no significant correlation between the NBT level and age, gender,
duration of diabetes, daily insulin usage and blood HbA1C level. CONCLUSIONS:
Compared to non-diabetics, respiratory burst process of polymorphonuclears is
obviously decreased in diabetic children. This can explain one of the mechanisms
involved in the increased rate of infections in DM.
PMID- 27617068
TI - Evaluation of Serum Zinc Levels in Hyperbilirubinemic Neonates Before and After
Phototherapy.
AB - BACKGROUND: The existing therapeutic methods for neonatal jaundice are costly,
time-consuming and potentially risky. Zinc salts can reduce phototherapy duration
by precipitating unconjugated bilirubin in the intestine (bilirubin and zinc can
form a complex in physiologic pH); however, zinc toxicity is an issue that must
be considered since theoretically bilirubin reduction by phototherapy may
increase serum zinc levels, making additional zinc supplementation the potential
cause of zinc toxicity. OBJECTIVES: So, our purpose was evaluating the serum zinc
level alterations before and after phototherapy, in hyperbilirubinemic newborns.
MATERIALS AND METHODS: A prospective cohort study was performed at the children's
medical center of Tehran University of Medical Sciences from 2012 to 2014.
Healthy, full-term exclusively breast fed newborns with non-hemolytic jaundice
were enrolled in the study. Participants were divided into two groups based on
serum bilirubin levels (TSB < 18 mg/dL and TSB >= 18 mg/dL) at admission. Pre-
and post-phototherapy total serum zinc level was measured before and 12 - 24
hours after termination of phototherapy. RESULTS: Phototherapy was associated
with a significant increase in the serum zinc level in neonates with severe
hyperbilirubinemia (TSB >= 18 mg/dL) but not in those with mild-moderate
hyperbilirubinemia (TSB < 18 mg/dL). In addition, phototherapy caused a
significant increase in the rate of zinc with potentially toxic levels (zinc >
200) in only neonates with severe hyperbilirubinemia. CONCLUSIONS: Phototherapy
increases serum zinc level by reducing bilirubin level so that additional
supplementation of this element can lead potentially to zinc toxicity.
PMID- 27617069
TI - Prevent Sudden Death in Carvajal Syndrome With Left Ventricular
Hypertrabeculation/Noncompaction.
PMID- 27617072
TI - Incidentally Detected Persistent Left Superior Vena Cava With an Absent Right
Superior Vena Cava in a Neonate.
PMID- 27617071
TI - Fournier's Gangrene in a Neonate With Acute Myeloid Leukemia: A Case Report.
AB - INTRODUCTION: Fournier's gangrene is an infective necrotizing fasciitis of
external genital and perineal region. Hematologic malignancies and
immunocompromised status are predisposing factors. Simultaneous occurrence of
Fournier's gangrene and congenital leukemia in neonates is extremely rare. CASE
PRESENTATION: We present a case of Fournier's gangrene in a 4-day-old female
infant with a necrotic lesion in perineum and no history of trauma or other
predisposing condition. Focusing on high blast percentage in blood cell count she
was affected by acute myeloid leukemia (M4 type). Pseudomonas aeruginosa was
isolated from the blood and wound culture. She was treated with broad spectrum
antibiotics and supportive care. The parents refused chemotherapy and the patient
was discharged from hospital. Bleeding and DIC was the cause of death in a local
hospital few days later. CONCLUSIONS: High index of suspicion is essential for
diagnosis and appropriate treatment. Congenital leukemia should be considered in
the differential diagnosis of a newborn with clinical features of sepsis and
necrotizing fasciitis.
PMID- 27617070
TI - NT-proBNP in Children With Left to Right Shunt and Dilated Cardiomyopathy.
AB - BACKGROUND: B-type natriuretic peptide (BNP) levels are elevated in children with
congenital heart disease involving a left-to-right shunt (LRS) and are also
raised in dilated cardiomyopathy (DCM). As far as we know, there are few reports
in the literature comparing the change of the NT-proBNP in LRS and DCM especially
in the pediatric age group. OBJECTIVES: The aim of the study was to compare the
changes of the NT-proBNP in pediatric patients with LRS and DCM. Correlation
between the levels of NT-proBNP and the echocardiographic parameters in both
groups was determined. PATIENTS AND METHODS: A total of 30 children (13 males and
17 females) participated in the study. There were 11/30 (36.7%) DCM and 19/30
(63.3%) LRS. The control group consisted of 44 healthy infants and children.
Manifestations of heart failure (decompensation) were recorded. The NT-pro BNP
levels were measured. The following Echo parameters were assessed: systolic
function (ejection fraction and fraction shortening), pulmonary to systemic flow
(Qp/Qs) in LRS, pulmonary flow and pulmonary artery pressure (SPAP) and LV
diastolic function (E-wave, A-wave, E/A ratio and deceleration time). RESULTS:
Clinically 17/30 (56.7%) (11 of the LRS and 5 of the DCM) were decompensated.
Significant shunt was present in 15/19 (78.9%) in LRS. Systolic dysfunction was
presented in 5/30 (16.7%) cases (4 patients were DCM and one case was LRS). Two
types of diastolic dysfunction, impaired relaxation in 5/22 (22.7%) patients and
restrictive-like filling pattern in 5/16 (31.2 %) were observed. The NT-Pro BNP
level was significantly elevated 11 and 16 times in the LRS and DCM groups
respectively. Negative significant correlations were observed between the levels
of NT-ProBNP and the following echo variables; EDD, LAD, E wave and E/A ratio in
the LRS patients. Positive significant correlations were observed between the
levels of NT-ProBNP and the following echo variables; PAP and QP/QS in the LRS.
Both the PAP and QP/QS were higher in the elevated NT-Pro BNP group compared to
the normal level group. The NT-Pro BNP level was elevated in all 17/30 (56.7%)
decompensated patients (11 were LRS, 6 were DCM) (P = 0.002). However, the level
was elevated in only 7/13 (23.3%) of the compensated patients (3 were LRS, 4 were
DCM) (P = 0.002). The NT-Pro BNP level was also elevated in 18/19 cases with
pulmonary hypertension (P = 0.01). Finally, we conclude that the NT-ProBNP level
is elevated in both LRS and DCM in pediatric age. This elevation is more
remarkable with heart failure and increased PAP in both diseased groups. The
level was also elevated and correlated to Qp/Qs in the LRS patients. CONCLUSIONS:
So, we recommend the use of NT-ProBNP as a routine marker for following up
patients with heart failure and pulmonary hypertension in LRS and DCM.
PMID- 27617074
TI - Acute Intermittent Porphyria: A Diagnostic Challenge.
PMID- 27617073
TI - Changes of Platelet Indices in Juvenile Idiopathic Arthritis in Acute Phase and
After Two Months Treatment.
AB - BACKGROUND: Various indices have been raised as predictors of activity and
severity of juvenile idiopathic arthritis. OBJECTIVES: This study was conducted
to investigate the changes of platelet indices in acute phase and two months
after treatment in these patients. PATIENTS AND METHODS: In a cohort study,
platelet count, mean platelet volume (MPV), platelet distribution width (PDW),
plateletcrit (PCT) were evaluated in children referred to children's medical
center, Tehran due to juvenile idiopathic arthritis from March 2013 to March 2014
during the acute phase and two months after standard treatment. The statistical
data were analyzed by SPSS 19 software, and the significance level was set as P <
0.05. RESULTS: In this study, 55 children (24 boys and 31 girls) with mean +/- SD
age of 7.50 +/- 3.35 years were studied. The mean +/- SD value of platelet count
was 441872.7 +/- 151836.9 in the acute phase and reached 395418.2 +/- 119601.6
two months after treatment (P = 0.01). The mean +/- SD PCT in the acute phase of
various subtypes of the disease was 0.32 +/- 0.11, which reached 0.29 +/- 0.10
after treatment (P = 0.09). However, the PDW range in different subtypes of the
disease reached 13.4 +/- 8.0 from 13.9 +/- 2.9 and MPV reached 8.7 +/- 0.9 from
8.8 +/- 1.1 after treatment, but they were not significantly different from the
results in the acute phase (P = 0.5). CONCLUSIONS: Platelet count is one of the
most remarkable indices in JIA. Evaluation of PCT can also help determine the
severity of the inflammatory process in the follow-up and treatment process.
PMID- 27617075
TI - The Comparison of Participation in School-Aged Cerebral Palsy Children and Normal
Peers: A Preliminary Study.
AB - BACKGROUND: Participation in daily activities during childhood is an important
aspect for health and social development. OBJECTIVES: This study was designed to
investigate the participation of children with cerebral palsy aged 8 to 14 years,
and their normal peers. PATIENTS AND METHODS: In this cross-sectional study, 30
children with cerebral palsy, and 30 normal children were selected via the non
probability convenience sampling. Their participation was evaluated with
children's assessment of participation and enjoyment (CAPE) through interviews.
RESULTS: Significant differences were found between the means of the two groups
regarding the diversity, intensity, overall participation (P = 0.000) and all
types of the activities except the recreational activities. The children with
cerebral palsy took part in the skill-based activities and overall activities
individually compared to the normal peers. The children with cerebral palsy, in
comparison with their normal peers, often performed most of the activities inside
the house. The main effect of gender and the interaction between gender and
groups were not statistically significant in any of the variables of the CAPE
test. CONCLUSIONS: Physical disability can influence the children's daily
activities and socialization. Understanding the participation of physically
disabled children can help health care professionals in designing and introducing
appropriate treatment according to their needs.
PMID- 27617076
TI - Detection of Early Right Ventricular Dysfunction in Young Patients With
Thalassemia Major Using Tissue Doppler Imaging.
AB - BACKGROUND: Myocardial iron overload is the most common cause of mortality in
patients with thalassemia major (TM), also known as beta-thalassemia. T2*
cardiovascular magnetic resonance imaging (MRI) is the best way of monitoring
cardiac iron, and new echocardiographic techniques can be used to assess cardiac
function. OBJECTIVES: The aim of this study was to assess the systolic and
diastolic right ventricular (RV) function of patients with TM using tissue
Doppler imaging (TDI) and to determine whether this echocardiographic technique
is an adequate diagnostic tool for the screening and detection of subclinical
cardiac dysfunction. PATIENTS AND METHODS: Eighty-four patients with TM were
evaluated by conventional echocardiography and pulse-wave TDI. The data of the TM
group (Group 1) were compared with that of 85 age- and sex-matched healthy
controls (Group 2). Cardiovascular T2* MRI examinations were performed in 49 of
the 85 patients. RESULTS: The patients with TM had significantly lower values for
weight, height, body mass index, systolic arterial pressure, deceleration time,
E'/A', and ejection time (ET) than the controls. Group 1 also had significantly
higher values for peak early diastolic velocity (E) over peak late diastolic
velocity (A), peak early diastolic velocity of TDI (E'), peak late diastolic
velocity of TDI (A'), E/E', isovolumetric relaxation time, isovolumetric
contraction time, and RV magnetic perfusion imaging (MPI) than Group 2.
CONCLUSIONS: RV diastolic dysfunction occurs before systolic deterioration in
patients with TM and cannot be screened with conventional echocardiographic
techniques. In routine practice, TDI measurements, MPI (for global function) and
the E/E' parameter (for diastolic function) can be used to screen and detect
early RV dysfunction.
PMID- 27617077
TI - Efficacy of Post-Exposure Prophylaxis in Infants Born to HBsAg Positive Mothers
in Iran; Is It Authentic?
AB - BACKGROUND: Hepatitis B infection is a universal concern. This infection can lead
to chronic liver disease and hepatocellular carcinoma. Neonates born to HBsAg
positive mothers are at high risk of chronic hepatitis B virus (HBV) infection,
especially for HBeAg-positive mothers or neonates who have not received hepatitis
B immunoglobulin (HBIg) and HBV vaccines. OBJECTIVES: The aim of this study was
to evaluate the efficacy of post-exposure prophylaxis in these infants to prevent
infection. PATIENTS AND METHODS: Thirty-eight infants born to HBsAg-positive
mothers between September 2006 and September 2013 were followed. The
investigation evaluated whether the standard prevention protocol of neonatal HBV
transmission including HBIg at birth and receiving three doses of vaccine at
birth and 2 and 6 months of age was performed, followed by post-vaccination tests
(evaluation of HBsAg and HBsAb titer at 9 to 18 months of age) to determine
subsequent infection. HBsAb titer >= 10 was considered as criterion for
effectiveness of the prophylaxis procedure. The acquired data were analyzed using
SPSS software (Version 18). The results are reported in descriptive tabulations.
RESULTS: Ninety seven percent (97%) of infants received HBIg at birth in the
hospital. Generally, all of them received the first, second and third doses of
vaccine at birth, 2 months, and 6 months after birth, respectively. Information
for 35 mothers infected with HBV and 38 infants was available. The mean age of
the mothers was 30.3 years. The results indicated that 20% of mothers were HBeAg
positive. HBsAg was positive in one (2.6%) infant born to an HBeAg-positive
mother. Around 94% of infants' HBsAb titers were >= 10, and 5.8% were reported as
non-responders. CONCLUSIONS: The vertical transmission prevention program used in
the study population in Tehran, which had an appropriate sample size, is
effective. Additional doses of the vaccine can be useful in raising the
effectiveness of immunoprophylaxis for infants at high risk of HBV infection.
Also, emphasis must be set on post-vaccination testing.
PMID- 27617078
TI - Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed
Using Destiny Plus.
AB - BACKGROUND: In order to apply the right treatment for hemostatic disorders in
pediatric patients, laboratory data should be interpreted with age-appropriate
reference ranges. OBJECTIVES: The purpose of this study was to determining age
dependent reference range values for prothrombin time (PT), activated partial
thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. MATERIALS AND
METHODS: A total of 320 volunteers were included in the study with the following
ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11
17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a
survey to exclude hemostatic system disorder. Using a nonparametric method, the
lower and upper limits, including 95% distribution and 90% confidence intervals,
were calculated. RESULTS: No statistically significant differences were found
between PT and aPTT values in the groups consisting of children. Thus, the
reference ranges were separated into child and adult age groups. PT and aPTT
values were significantly higher in the children than in the adults. Fibrinogen
values in the 6 - 10 age group and the adult age group were significantly higher
than in the other groups. D-dimer levels were significantly lower in those aged 2
- 17; thus, a separate reference range was established. CONCLUSIONS: These
results support other findings related to developmental hemostasis, confirming
that adult and pediatric age groups should be evaluated using different reference
ranges.
PMID- 27617079
TI - Controlling amphiphilic copolymer self-assembly morphologies based on
macrocycle/anion recognition and nucleotide-induced payload release.
AB - We report here a new approach to creating diversiform copolymer-derived self
assembly morphologies that relies on macrocycle/anion recognition in aqueous
media. This approach exploits the anion binding features of a water-soluble form
of the so-called 'Texas-sized' molecular box. When this tetracationic receptor is
added to an aqueous solution of an amphiphilic copolymer bearing tethered
carboxylate anion substituents, binding occurs to form a macrocycle/polymer
complex. As the concentration of the box-like receptor increases, the relative
hydrophilic fraction of the copolymer complex likewise increases. This leads to
changes in the overall morphology of the self-assembled ensemble. The net result
is an environmentally controllable system that mimics on a proof-of-concept level
the structural evolution of organelles seen in living cells. The macrocycle/anion
interactions respond in differing degrees to three key biological species, namely
ATP, ADP, and AMP, which may be used as "inputs" to induce disassembly of these
vehicles. As a result of this triggering and the nature of the morphological
changes induced, the present copolymer system is capable of capturing and
releasing in controlled manner various test payloads, including hydrophobic and
hydrophilic fluorophores. The copolymer displays low inherent cytotoxicity as
inferred from cell proliferation assays involving the HUVEC and HepG2 cell lines.
PMID- 27610219
TI - Detecting variable responses in time-series using repeated measures ANOVA:
Application to physiologic challenges.
AB - We present an approach to analyzing physiologic timetrends recorded during a
stimulus by comparing means at each time point using repeated measures analysis
of variance (RMANOVA). The approach allows temporal patterns to be examined
without an a priori model of expected timing or pattern of response. The approach
was originally applied to signals recorded from functional magnetic resonance
imaging (fMRI) volumes-of-interest (VOI) during a physiologic challenge, but we
have used the same technique to analyze continuous recordings of other
physiological signals such as heart rate, breathing rate, and pulse oximetry. For
fMRI, the method serves as a complement to whole-brain voxel-based analyses, and
is useful for detecting complex responses within pre-determined brain regions, or
as a post-hoc analysis of regions of interest identified by whole-brain
assessments. We illustrate an implementation of the technique in the statistical
software packages R and SAS. VOI timetrends are extracted from conventionally
preprocessed fMRI images. A timetrend of average signal intensity across the VOI
during the scanning period is calculated for each subject. The values are scaled
relative to baseline periods, and time points are binned. In SAS, the procedure
PROC MIXED implements the RMANOVA in a single step. In R, we present one option
for implementing RMANOVA with the mixed model function "lme". Model diagnostics,
and predicted means and differences are best performed with additional libraries
and commands in R; we present one example. The ensuing results allow
determination of significant overall effects, and time-point specific within- and
between-group responses relative to baseline. We illustrate the technique using
fMRI data from two groups of subjects who underwent a respiratory challenge.
RMANOVA allows insight into the timing of responses and response differences
between groups, and so is suited to physiologic testing paradigms eliciting
complex response patterns.
PMID- 27617081
TI - The Ligands of Neutrophil Gelatinase-Associated Lipocalin.
AB - Neutrophil gelatinase associated lipocalin (NGAL), was originally identified in
neutrophil granules as a heterodimer complex with gelatinase B (matrix
metalloproteinase 9, MMP9), but more recently has been found to be secreted by
damaged epithelial cells. Ngal is a member of the lipocalin family and
subsequently named as lipocalin 2 on the basis of structural similarity with
other members of the lipocalin family and its potential association with
hydrophobic retinol and cholesterol oleate more strongly than their hydrophilic
counterparts. In 2002, a landmark paper suggested that Ngal is a bacteriostatic
agent which blocks iron acquisition by interacting with a number of bacterial
siderophores, especially enterobactin. Since then, more siderophore-carrying
functions have been reported than the possibility of hydrophobic ligand
transport. In this setting, Ngal was renamed Siderocalin. Functions of
siderocalin include not only bacteriostatic activity but potentially as a
mediator of cell growth and differentiation; some of these functions appear to be
referable to the holo siderocalin:siderophore:iron complex and recent work
suggests that metabolic products may act as mammalian siderophores bound by Ngal.
While still speculative, it may be that the mammalian siderophores can establish
the missing link between Ngal and a number of its functions in vivo. This review
provides an overview of the discoveries of the different ligands of Ngal and
consequently related functions. Hydrophobic ligands, bacterial siderophores as
well as their modified structures (synthetic siderophores), and mammalian
siderophores are summarized.
PMID- 27617083
TI - Using vibrational infrared biomolecular spectroscopy to detect heat-induced
changes of molecular structure in relation to nutrient availability of prairie
whole oat grains on a molecular basis.
AB - BACKGROUND: To our knowledge, there is little study on the interaction between
nutrient availability and molecular structure changes induced by different
processing methods in dairy cattle. The objective of this study was to
investigate the effect of heat processing methods on interaction between nutrient
availability and molecular structure in terms of functional groups that are
related to protein and starch inherent structure of oat grains with two continued
years and three replication of each year. METHOD: The oat grains were kept as raw
(control) or heated in an air-draft oven (dry roasting: DO) at 120 degrees C for
60 min and under microwave irradiation (MIO) for 6 min. The molecular structure
features were revealed by vibrational infrared molecular spectroscopy. RESULTS:
The results showed that rumen degradability of dry matter, protein and starch was
significantly lower (P <0.05) for MIO compared to control and DO treatments. A
higher protein alpha-helix to beta-sheet and a lower amide I to starch area ratio
were observed for MIO compared to DO and/or raw treatment. A negative correlation
(-0.99, P < 0.01) was observed between alpha-helix or amide I to starch area
ratio and dry matter. A positive correlation (0.99, P < 0.01) was found between
protein beta-sheet and crude protein. CONCLUSION: The results reveal that oat
grains are more sensitive to microwave irradiation than dry heating in terms of
protein and starch molecular profile and nutrient availability in ruminants.
PMID- 27617084
TI - Cardiac Resynchronisation Therapy: The Optimal QRS Duration Revisited.
PMID- 27617085
TI - The European Heart Rhythm Association: A Myriad of Benefits and Privileges.
PMID- 27617082
TI - Osteoporosis drug effects on cortical and trabecular bone microstructure: a
review of HR-pQCT analyses.
AB - With the development of new non-invasive analytical techniques and particularly
the advent of high-resolution peripheral quantitative computed tomography
(HRpQCT) it is possible to assess cortical and trabecular bone changes under the
effects of ageing, diseases and treatments. In the present study, we reviewed the
treatment-related effects on bone parameters assessed by HRpQCT imaging. We
identified 12 full-length articles published in peer-reviewed journals describing
treatment-induced changes assessed by HRpQCT. The design of these studies varied
a lot in terms of duration and methodology: some of them were open-labelled,
others were double-blind, placebo-controlled or double-blind, double-dummy,
active controlled. In addition, the sample size in these studies ranged from 11
to 324 patients. Motion artifacts occurring during data acquisition were
sometimes a real challenge particularly at the radius leading sometimes to
exclude the analysis at the radius due to the uninterpretability of
microstructural parameters. Responses to therapies were treatment-specific and
divergent effects in cortical and trabecular bone with antiresorptive or anabolic
agents were observed. Standardization of bone microarchitecture parameters
(including porosity) and bone strength estimates by finite element analysis (FEA)
are mandatory. The additional value of microarchitecture and FEA estimates
changes with therapies in terms of improvement in fracture outcomes which have to
be adequately assessed in clinical trials with fracture end point. Data from
these reviewed studies advance our understanding of the microstructural
consequences of osteoporosis and highlight potential differences in bone quality
outcomes within therapies.
PMID- 27617086
TI - Brugada Syndrome and Early Repolarisation: Distinct Clinical Entities or
Different Phenotypes of the Same Genetic Disease?
AB - Brugada and early repolarisation (ER) syndromes are currently considered two
distinct inherited electrical disorders with overlapping clinical and
electrocardiographic features. A considerable number of patients diagnosed with
ER syndrome have a genetic mutation related to Brugada syndrome (BrS). Due to the
high variable phenotypic manifestation, patients with BrS may present with
inferolateral repolarisation abnormalities only, resembling the ER pattern.
Moreover, the complex genotype-phenotype interaction in BrS can lead to the
occurrence of mixed phenotypes with ER syndrome. The first part of this review
focuses on specific clinical and electrocardiographic features of BrS and ER
syndrome, highlighting the similarity shared by the two primary electrical
disorders. The genetic background, with emphasis on the complexity of genotype
phenotype interaction, is explored in the second part of this review.
PMID- 27617089
TI - The Significance of Shocks in Implantable Cardioverter Defibrillator Recipients.
AB - Large-scale implantable cardioverter defibrillator (ICD) trials have
unequivocally shown a reduction in mortality in appropriately selected patients
with heart failure and depressed left ventricular function. However, there is a
strong association between shocks and increased mortality in ICD recipients. It
is unclear if shocks are merely a marker of a more severe cardiovascular disease
or directly contribute to the increase in mortality. The aim of this review is to
examine the relationship between ICD shocks and mortality, and explore possible
mechanisms. Data examining the effect of shocks in the absence of spontaneous
arrhythmias as well as studies of non-shock therapy and strategies to reduce
shocks are analysed to try and disentangle the shocks versus substrate debate.
PMID- 27617088
TI - Individualising Anticoagulant Therapy in Atrial Fibrillation Patients.
AB - Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as
alternatives to VKAs for the prevention of stroke in patients with non-valvular
atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban,
have received regulatory approval in Europe from the European Medicines Agency.
Numerous factors can influence the decision to prescribe a NOAC, the most
important of which are assessment of stroke and bleeding risks. Given the
variation in design of the pivotal phase III clinical trials investigating the
efficacy and safety of NOACs, and in the absence of head-to-head comparative
data, it is impossible to recommend one NOAC over the other. However, NOACS offer
the opportunity for individualised therapy based on factors such as renal
function, age or patient/doctor preference for once- or twice-daily dosing
regimens. Dose reduction of some NOACS should be considered in at-risk patient
populations.
PMID- 27617090
TI - Antiarrhythmic Drug Therapy to Avoid Implantable Cardioverter Defibrillator
Shocks.
AB - Implantable cardioverter defibrillators (ICDs) are effective in the prevention of
arrhythmic sudden cardiac death. Many patients receiving an ICD are affected by
heart failure and are at risk of ventricular arrhythmias, which may lead to
appropriate shocks. On the other hand, in this population the incidence of atrial
fibrillation, giving rise to inappropriate ICD shocks, is high. Accordingly, ICD
discharges occur frequently and many patients with an ICD will need concomitant
antiarrhythmic drug therapy to avoid or reduce the frequency of shocks.
Therapeutic agents such as beta-blockers, class I or class III antiarrhythmic
drugs effectively suppress arrhythmias, but may have side-effects. Some drugs
could eventually influence the function of ICDs by altering defibrillation or
pacing threshold. Few prospective randomised trials are available, but current
data suggest that amiodarone is most effective for prevention of appropriate or
inappropriate ICD shocks. This review article summarises current knowledge
regarding the antiarrhythmic management of patients with ICDs.
PMID- 27617087
TI - Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes.
AB - This overview gives an update on the molecular mechanisms, clinical
manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM
is mostly hereditary and associated with mutations in genes encoding proteins of
the intercalated disc. Three subtypes have been proposed: the classical right
dominant subtype generally referred to as ARVC/D, biventricular forms with early
biventricular involvement and left-dominant subtypes with predominant LV
involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and
sudden cardiac arrest due to ventricular arrhythmias, which typically occur in
athletes. At later stages, heart failure may occur. Diagnosis is established with
the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM
diagnosis, including both echocardiography and cardiac magnetic resonance imaging
for detecting functional and structural alternations. Of note, structural
findings often become visible after electrical alterations, such as premature
ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia
(VT). 12-lead ECG is important to assess for depolarisation and repolarisation
abnormalities, including T-wave inversions as the most common ECG abnormality.
Family history and the detection of causative mutations, mostly affecting the
desmosome, have been incorporated in the TFC, and stress the importance of
cascade family screening. Differential diagnoses include idiopathic right
ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease,
myocarditis, dilated cardiomyopathy, athlete's heart, Brugada syndrome and RV
infarction. Therapeutic strategies include restriction from endurance and
competitive sports, beta-blockers, antiarrhythmic drugs, heart failure
medication, implantable cardioverter-defibrillators and endocardial/epicardial
catheter ablation.
PMID- 27617091
TI - Management of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and
Vasovagal Syncope.
AB - Postural tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST) and
vasovagal syncope (VVS) are relatively common clinical syndromes that are seen by
physicians in several disciplines. They are often not well recognised and are
poorly understood by physicians, are associated with significant morbidity and
cause significant frustration for both patients and their physicians. The 2015
Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of
Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia and Vasovagal
Syncope provides physicians with an introduction to these disorders and initial
recommendations on their investigation and treatment. Here we summarise the
consensus statement to help physicians in the management of patients with these
frequently distressing problems.
PMID- 27617092
TI - Classification, Electrophysiological Features and Therapy of Atrioventricular
Nodal Reentrant Tachycardia.
AB - Atrioventricular nodal reentrant tachycardia (AVNRT) should be classified as
typical or atypical. The term 'fast-slow AVNRT' is rather misleading. Retrograde
atrial activation during tachycardia should not be relied upon as a diagnostic
criterion. Both typical and atypical atrioventricular nodal reentrant tachycardia
are compatible with varying retrograde atrial activation patterns. Attempts at
establishing the presence of a 'lower common pathway' are probably of no
practical significance. When the diagnosis of AVNRT is established, ablation
should be only directed towards the anatomic position of the slow pathway. If
right septal attempts are unsuccessful, the left septal side should be tried.
Ablation targeting earliest atrial activation sites during typical
atrioventricular nodal reentrant tachycardia or the fast pathway in general for
any kind of typical or atypical atrioventricular nodal reentrant tachycardia, are
not justified. In this review we discuss current concepts about the tachycardia
circuit, electrophysiologic diagnosis, and ablation of this arrhythmia.
PMID- 27617093
TI - Holter Monitoring and Loop Recorders: From Research to Clinical Practice.
AB - Holter monitors are tools of proven efficacy in diagnosing and monitoring cardiac
arrhythmias. Despite the fact their use is widely prescribed by general
practitioners, little is known about their evolving role in the management of
patients with cryptogenic stroke, paroxysmal atrial fibrillation, unexplained
recurrent syncope and risk stratification in implantable cardioverter
defibrillator or pacemaker candidates. New Holter monitoring technologies and
loop recorders allow prolonged monitoring of heart rhythm for periods from a few
days to several months, making it possible to detect infrequent arrhythmias in
patients of all ages. This review discusses the advances in this area of
arrhythmology and how Holter monitors have improved the clinical management of
patients with suspected cardiac rhythm diseases.
PMID- 27617094
TI - Reduction of Fluoroscopy Time and Radiation Dosage During Catheter Ablation for
Atrial Fibrillation.
AB - Radiofrequency catheter ablation has become the treatment of choice for atrial
fibrillation (AF) that does not respond to antiarrhythmic drug therapy. During
the procedure, fluoroscopy imaging is still considered essential to visualise
catheters in real-time. However, radiation is often ignored by physicians since
it is invisible and the long-term risks are underestimated. In this respect, it
must be emphasised that radiation exposure has various potentially harmful
effects, such as acute skin injury, malignancies and genetic disease, both to
patients and physicians. For this reason, every electrophysiologist should be
aware of the problem and should learn how to decrease radiation exposure by both
changing the setting of the system and using complementary imaging technologies.
In this review, we aim to discuss the basics of X-ray exposure and suggest
practical instructions for how to reduce radiation dosage during AF ablation
procedures.
PMID- 27617095
TI - Anatomical Substrates and Ablation of Reentrant Atrial and Ventricular
Tachycardias in Repaired Congenital Heart Disease.
AB - Advances in surgical repair techniques for various types of congenital heart
disease have improved survival into adulthood over the past decades, thus
exposing these patients to a high risk of atrial and ventricular arrhythmias
later in life. These arrhythmias arise from complex arrhythmogenic substrates.
Substrate formation may depend on both pathological myocardial remodelling and
variable anatomical boundaries, determined by the type and timing of prior
corrective surgery. Accordingly, arrhythmogenic substrates after repair have
changed as a result of evolving surgical techniques. Radiofrequency catheter
ablation offers an important therapeutic option but remains challenging due to
the variable anatomy, surgically created obstacles and the complex arrhythmogenic
substrates. Recent technical developments including electroanatomical mapping and
image integration for delineating the anatomy facilitate complex catheter
ablation procedures. The purpose of this review is to provide an update on the
changing anatomical arrhythmogenic substrates and their potential impact on
catheter ablation in patients with repaired congenital heart disease and
tachyarrhythmias.
PMID- 27617096
TI - A new intervention for people with borderline personality disorder who are also
parents: a pilot study of clinician acceptability.
AB - BACKGROUND: Engaging parents who have a personality disorder in interventions
designed to protect children from the extremes of the disorder supports both
parenting skills and healthy child development. In line with evidence-based
guidelines, a 'Parenting with Personality Disorder' brief intervention was
developed, focusing on child safety, effective communication and parenting
strategies. METHOD: Ratings of acceptability for the brief intervention model
were given by 168 mental health clinicians who attended training. Changes in
clinician attitudes, knowledge and skills were also assessed following training.
RESULTS: Providing clinicians treating personality disorder clients with
additional skills to address parenting was well received and filled a gap in
service provision. Clinicians reported improvements in clinical skills,
knowledge, willingness and confidence to intervene in parenting issues with
clients. Qualitative responses endorsed three major modes of learning: case study
analysis, reflective learning activities, and skills-based intervention
practices. CONCLUSIONS: Current treatment guidelines emphasise addressing
parenting, but no evidence-based therapy includes specific parenting skills. This
brief intervention model improved skills, efficacy and willingness to intervene.
This approach can be readily added to current evidence-based therapy protocols
and promises to improve client functioning and protect children from the extremes
of the disorder. Clinical trials are now required to validate the approach in the
field.
PMID- 27617099
TI - Prescription medicine sharing: exploring patients' beliefs and experiences.
AB - BACKGROUND: Prescription medicine sharing has been defined as the lending of
medicines (giving prescription medicines to someone else) or borrowing of
medicines (being given and using a medicine prescribed for another person). This
qualitative study explored the views of patients, to elicit information regarding
factors influencing medicine sharing behaviours, their experiences of the
consequences of prescription medicine sharing, and their risk assessment
strategies when deciding to share. METHODS: One-on-one, face-to-face, semi
structured interviews were carried out in Auckland, New Zealand between September
2013 and August 2014 with 17 patients, purposively sampled to provide information
from different socio-demographic backgrounds. The interviews were audio recorded,
transcribed verbatim and analysed using a general inductive approach. The study
received ethical approval, and all interviewees provided written informed
consent. RESULTS: Findings were captured within five overarching themes: types of
shared medicines; perceived benefits of sharing medicines; negative experiences
of sharing; factors influencing sharing behaviours; and risk assessment
strategies. Participants reported that sharing helped them to avoid treatment
costs and the inconvenience associated with medical visits such as booking
appointments. Conversely, unanticipated side effects, allergies, and taking
inappropriate medicines were the main adverse consequences of sharing. Altruism,
limited access to medicines/health services, sociocultural factors, and having
unused prescription medicines were factors influencing sharing behaviours.
Participants reported assessing the safety of sharing a medicine primarily based
on symptom matching, past illness experiences, and knowledge about the medicines.
CONCLUSIONS: This study enriches previous survey findings, by providing insight
into patients' reasons for medicines sharing. Healthcare providers should
consider asking their patients about any medicines they have shared and their
future sharing intentions, in order to use the opportunity for discussing safer
sharing practices, without promoting the behaviour. The findings are helpful for
informing the development of potential interventions and targeted educational
messages about safe medicine use for patients.
PMID- 27617100
TI - Association between employment status and self-rated health: Korean working
conditions survey.
AB - BACKGROUND: This research was conducted with an aim of determining the
association between employment status and self-rated health. METHODS: Using the
data from the Third Korean Working Conditions Survey conducted in 2011, We
included data from 34,783 respondents, excluding employers, self-employed
workers, unpaid family workers, others. Self-rated health was compared according
to employment status and a logistic regression analysis was performed. RESULTS:
Among the 34,783 workers, the number of permanent and non-permanent workers was
27,564 (79.2 %) and 7,219 (20.8 %). The risk that the self-rated health of non
permanent workers was poor was 1.20 times higher when both socio-demographic
factors, work environment and work hazards were corrected. CONCLUSIONS: In this
study, perceived health was found to be worse in the non-permanent workers than
permanent workers. Additional research should investigate whether other factors
mediate the relationship between employment status and perceived health.
PMID- 27617097
TI - Glycocalyx and its involvement in clinical pathophysiologies.
AB - Vascular hyperpermeability is a frequent intractable feature involved in a wide
range of diseases in the intensive care unit. The glycocalyx (GCX) seemingly
plays a key role to control vascular permeability. The GCX has attracted the
attention of clinicians working on vascular permeability involving angiopathies,
and several clinical approaches to examine the involvement of the GCX have been
attempted. The GCX is a major constituent of the endothelial surface layer (ESL),
which covers most of the surface of the endothelial cells and reduces the access
of cellular and macromolecular components of the blood to the surface of the
endothelium. It has become evident that this structure is not just a barrier for
vascular permeability but contributes to various functions including signal
sensing and transmission to the endothelium. Because GCX is a highly fragile and
unstable layer, the image had been only obtained by conventional transmission
electron microscopy. Recently, advanced microscopy techniques have enabled direct
visualization of the GCX in vivo, most of which use fluorescent-labeled lectins
that bind to specific disaccharide moieties of glycosaminoglycan (GAG) chains.
Fluorescent-labeled solutes also enabled to demonstrate vascular leakage under
the in vivo microscope. Thus, functional analysis of GCX is advancing. A
biomarker of GCX degradation has been clinically applied as a marker of vascular
damage caused by surgery. Fragments of the GCX, such as syndecan-1 and/or
hyaluronan (HA), have been examined, and their validity is now being examined. It
is expected that GCX fragments can be a reliable diagnostic or prognostic
indicator in various pathological conditions. Since GCX degradation is strongly
correlated with disease progression, pharmacological intervention to prevent GCX
degradation has been widely considered. HA and other GAGs are candidates to
repair GCX; further studies are needed to establish pharmacological intervention.
Recent advancement of GCX research has demonstrated that vascular permeability is
not regulated by simple Starling's law. Biological regulation of vascular
permeability by GCX opens the way to develop medical intervention to control
vascular permeability in critical care patients.
PMID- 27617098
TI - Whole genome sequencing of emerging multidrug resistant Candida auris isolates in
India demonstrates low genetic variation.
AB - Candida auris is an emerging multidrug resistant yeast that causes nosocomial
fungaemia and deep-seated infections. Notably, the emergence of this yeast is
alarming as it exhibits resistance to azoles, amphotericin B and caspofungin,
which may lead to clinical failure in patients. The multigene phylogeny and
amplified fragment length polymorphism typing methods report the C. auris
population as clonal. Here, using whole genome sequencing analysis, we decipher
for the first time that C. auris strains from four Indian hospitals were highly
related, suggesting clonal transmission. Further, all C. auris isolates
originated from cases of fungaemia and were resistant to fluconazole (MIC >64
mg/L).
PMID- 27617101
TI - Effects of computer familiarity and computer type on the performance of Korean
computerized neurobehavioral test.
AB - BACKGROUND: It is thought that computer familiarity has increased significantly
since 2004 as well as the use of computers. This study aimed to evaluate the
effects of computer familiarity and types of keyboard and computer on the
performance of the Korean computerized neurobehavioral test (KCNT), and to
identify which parameters of KCNT were affected by aforementioned factors.
METHODS: A total of 85 subjects were classified into three groups of computer
familiarity by Korean typing speed. Their age, gender and the level of education
were also collected. The parameters of KCNT included simple reaction time, choice
reaction time, addition, symbol digit, and finger tapping speed. The test was
conducted using three types of computers: a laptop computer, a laptop computer
with a simplified keyboard, and a desktop computer with a simplified keyboard.
RESULTS: Parameters including the simple reaction time, choice reaction time,
addition, and symbol digit, and the finger tapping speed of non-dominant hand
showed no significant differences in the results among the three groups by
computer familiarity after age and educational years were controlled as
covariates. The mean reaction time of the simple reaction time and the choice
reaction time with a simplified keyboard was significantly shorter compared to
that with a typical keyboard. With regard to type of computer, the mean reaction
time of the simple reaction time and the choice reaction time was significantly
reduced when performed with the desktop computer with a simplified keyboard.
CONCLUSIONS: Unlike previous study results, the choice reaction time, the
addition, and the finger tapping speed of dominant hand were the only parameters
affected by the computer familiarity. Both the type of keyboard and the type of
computer significantly influenced the simple reaction time and the choice
reaction time. Therefore, it is recommended to use a desktop computer with a
simplified keyboard for such parameters.
PMID- 27617102
TI - Reliability and validity of the workplace harassment questionnaire for Korean
finance and service workers.
AB - BACKGROUND: Harassment means systemic and repeated unethical acts. Research on
workplace harassment have been conducted widely and the NAQ-R has been widely
used for the researches. But this tool, however the limitations in revealing
differended in sub-factors depending on the culture and in reflecting that unique
characteristics of the Koren society. So, The workplace harassment questionnaire
for Korean finace and service workers has been developed to assess the level of
personal harassment at work. This study aims to develop a tool to assess the
level of personal harassment at work and to test its validity and reliability
while examining specific characteristics of workplace harassment against finance
and service workers in Korea. METHODS: The framework of survey was established
based on literature review, focused-group interview for the Korean finance and
service workers. To verify its reliability, Cronbach's alpha coefficient was
calculated; and to verify its validity, items and factors of the tool were
analyzed. The correlation matrix analysis was examined to verify the tool's
convergent validity and discriminant validity. Structural validity was verified
by checking statistical significance in relation to the BDI-K. RESULTS:
Cronbach's alpha coefficient of this survey was 0.93, which indicates a quite
high level of reliability. To verify the appropriateness of this survey tool, its
construct validity was examined through factor analysis. As a result of the
factor analysis, 3 factors were extracted, explaining 56.5 % of the total
variance. The loading values and communalities of the 20 items were 0.85 to 0.48
and 0.71 to 0.46. The convergent validity and discriminant validity were analyzed
and rate of item discriminant validity was 100 %. Finally, for the concurrent
validity, We examined the relationship between the WHI-KFSW and pschosocial
stress by examining the correlation with the BDI-K. The results of chi-square
test and multiple logistic analysis indicated that the correlation with the BDI-K
was satatisctically significant. CONCLUSION: Workplace harassment in actual
workplaces were investigated based on interviews, and the statistical analysis
contributed to systematizing the types of actual workplace harassment. By
statistical method, we developed the questionare, 20 items of 3 categories.
PMID- 27617103
TI - Leptomeningeal carcinomatosis in non-small-cell lung cancer: initial response to
erlotinib followed by relapse despite continuing radiological resolution of
disease.
AB - A 60-year-old male was diagnosed with T3, N3, M1b epidermal growth factor
receptor (EGFR) mutant lung adenocarcinoma. Five months later he developed
significant headaches, weakness and numbness of the left leg, and unsteadiness of
gait. Magnetic resonance imaging (MRI) brain demonstrated subtle gyral
enhancement indicative of early leptomeningeal infiltration. He was commenced on
second-line erlotinib which improved his lower limb symptoms. Three months later
he developed increased urinary frequency and redeveloped leg symptoms. MRI brain
showed improvement in the gyral enhancement. Four weeks later, the patient
developed new onset confusion and decrease in mobility. Examination of the
cerebrospinal fluid (CSF) demonstrated leptomeningeal carcinomatosis. This case
demonstrates radiological and clinical response of leptomeningeal disease to
erlotinib in EGFR mutant lung cancer with subsequent clinical relapse despite
continued radiological resolution of leptomeningeal disease. This suggests that
CSF examination should be considered when monitoring leptomeningeal disease
response following treatment as the disease can be undetectable on repeat
radiological imaging.
PMID- 27617104
TI - Tough decisions in pulmonary embolism: thrombolysis or embolectomy?
PMID- 27617105
TI - An unusual pain in the hip.
AB - A 68-year-old previously healthy man presented with increasing right hip pain of
6 months duration. On examination he was found to have a hard mass in the right
hip arising from the pelvic bone. Imaging studies were in keeping with a sarcoma
arising from the right iliac bone. However, biopsy of this bony lesion confirmed
this to be a metastatic adenocarcinoma rather than a primary bone malignancy.
Further imaging and a subsequent colonoscopy revealed the primary to be a colonic
adenocarcinoma. The unique and unusual nature of this case was the presentation
as a solitary bony metastasis from a colonic primary. There is no previously
documented report in the literature of such a rare presentation of a colonic
adenocarcinoma as a solitary bony lesion mimicking a primary sarcoma in the
absence of other signs or symptoms.
PMID- 27617106
TI - Progressive foot drop caused by below-knee compression stocking after spinal
surgery.
AB - Foot drop is a debilitating condition, which may take many months to recover. The
most common cause of foot drop is a neuropathy of the common peroneal nerve
(CPN). However, similar symptoms can be caused by proximal lesions of the sciatic
nerve, lumbar plexus or L5 nerve root. We present a rare and unusual case of a
patient undergoing spinal surgery at the level of L5/S1 and presenting 4 weeks
postoperatively with progressive foot drop. Although the initial concern was a
postoperative lesion at L5, the cause for this delayed presentation was extrinsic
compression of the CPN at the level of the fibular head by a tight-fitting below
knee thromboembolic deterrent stocking. Compression stockings are widely used in
all branches of medicine and in the community. It is important to recognize this
potential cause of progressive foot drop early as it is preventable by simple
measures, which can significantly reduce morbidity.
PMID- 27617107
TI - Letter regarding article 'Freezing of gait associated with a corpus callosum
lesion'.
AB - Here, I discuss the report by Dale et al. and present some relevant comments,
hoping that it will allow a better understanding of the patient's situation as
well as freezing of gait phenomenon. I will also discuss other disorders for
differential diagnosis those should be kept in mind.
PMID- 27617108
TI - Recruitment of Minority Adolescents and Young Adults into Randomised Clinical
Trials: Testing the Design of the Technology Enhanced Community Health Nursing
(TECH-N) Pelvic Inflammatory Disease Trial.
AB - PURPOSE: Pelvic inflammatory disease (PID) disproportionately affects adolescent
and young adult (AYA) women and can negatively influence reproductive health
trajectories. Few randomized controlled trials (RCTs) have focused on strategies
to improve outpatient adherence or to reduce reproductive morbidity in this
population. This paper describes the research methods and preliminary
effectiveness of recruitment, retention, and intervention strategies employed in
a novel RCT designed to test a technology-enhanced community-health nursing (TECH
N) intervention among urban AYA with PID. METHODS: AYA women aged 13-25 years
were recruited during acute PID visits in outpatient clinics and emergency
departments (ED) to participate in this IRB-approved trial. Participants
completed an audio-computerized self-interview (ACASI), provided vaginal
specimens, and were randomized to standard treatment or the intervention.
Intervention participants received text-messaging support for 30 days and a
community health nurse (CHN) interventionist performed a home visit with clinical
assessment within 5 days after enrollment. All patients received a full course of
medications and completed research visits at 14-days (adherence), 30 days and 90
days with by an outreach worker. STI testing performed at the 30-and 90-day
visits. Exploratory analyses using descriptive statistics were conducted to
examine recruitment, retention, and follow-up data to test the overall design of
the intervention. RESULTS: In the first 48 months, 64% of 463 patients were
eligible for the study and 81.2% of 293 eligible patients were recruited for the
study (63.3%); 238 (81.2%) of eligible patients were enrolled. Most participants
were African American (95.6%) with a mean age of 18.6 (2.3). Ninety-four percent
of individuals assigned to the TECH-N intervention completed the nursing visits.
All completed visits have been within the 5-day window and over 90% of patients
in both arms have been retained over the 3-month follow-up period. Biological
data suggests a shift in the biological milieu with the predominance of Chlamydia
trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections.
CONCLUSIONS: Preliminary data from the TECH-N study demonstrated that urban, low
income, minority AYA with PID can effectively be recruited and retained to
participate in sexual and reproductive health RCTs with sufficient investment in
the design and infrastructure of the study. Community-based sexual health
interventions appear to be both feasible and acceptable in this population.
PMID- 27617109
TI - Krabbe Disease in the Arab World.
AB - The autosomal recessive inherited Krabbe disease (KD) is a devastating pediatric
lysosomal storage disorder affecting white matter of the brain. It is caused by
mutations in the gene coding for the lysosomal enzyme galactocerebrosidase. While
most patients present with symptoms within the first 6 months of life, others
present later in life throughout adulthood. The early infantile form of KD (EIKD)
is frequent in the Muslim Arab population in Israel, with a very high prevalence
of approximately 1/100 to 1/150 live births. The homozygous variant c.1582G > A
(p.D528N) was found to be responsible for EIKD in Palestinian Arab patients. KD
was reported in different Arab countries with much lower frequency. While most
Arab patients presented with EIKD, late infantile and late onset KD forms were
also reported. Most Arab patients presented with variable symptoms ranging from
EIKD to late onset KD, with variable clinical findings. Based on literature
studies, this review focuses on the clinical and molecular findings of KD
patients with Arab ancestry, and highlights the need for developing universal
genetic screening programs to overcome the under-reported status of KD prevalence
in Arabia. This is expected to improve the prognosis of the disease and promote
targeted molecular diagnostics to the Arab patients.
PMID- 27617110
TI - Genetics of Cleft Palate and Velopharyngeal Insufficiency.
AB - Velopharyngeal insufficiency (VPI) can occur in the setting of an unrepaired or
repaired cleft lip and palate. The rate of VPI has been documented as high as 33%
in some studies with higher rates of recurrences following surgery associated
with genetic syndromes such as 22q11.2 deletions. The primary cause of VPI in
these groups is still identified as the anatomic abnormalities of the velum. In
this review, the anatomy and physiology of the velum are discussed along with
genetic mutations associated with VPI.
PMID- 27617111
TI - 22q11.2 Deletion Syndrome: Laboratory Diagnosis and TBX1 and FGF8 Mutation
Screening.
AB - Velocardiofacial syndrome is one of the recognized forms of chromosome 22q11.2
deletion syndrome (22q11.2 DS) and has an incidence of 1 of 4,000 to 1 of 6,000
births. Nevertheless, the 22q11 deletion is not found in several patients with a
22q11.2 DS phenotype. In this situation, other chromosomal aberrations and/or
mutations in the T-box 1 transcription factor C (TBX1) gene have been detected in
some patients. A similar phenotype to that of the 22q11.2 DS has been reported in
animal models with mutations in fibroblast growth factor 8 (Fgf8) gene. To date,
FGF8 mutations have not been investigated in humans. We tested a strategy to
perform laboratory testing to reduce costs in the investigation of patients
presenting with the 22q11.2 DS phenotype. A total of 109 individuals with
clinical suspicion were investigated using GTG-banding karyotype, fluorescence in
situ hybridization, and/or multiplex ligation-dependent probe amplification. A
conclusive diagnosis was achieved in 33 of 109 (30.2%) cases. In addition,
mutations in the coding regions of TBX1 and FGF8 genes were investigated in
selected cases where 22q11.2 deletion had been excluded, and no pathogenic
mutations were detected in both genes. This study presents a strategy for
molecular genetic characterization of patients presenting with the 22q11.2 DS
using different laboratory techniques. This strategy could be useful in different
countries, according to local resources. Also, to our knowledge, this is the
first investigation of FGF8 gene in humans with this clinical suspicion.
PMID- 27617112
TI - Partial Deletion of Chromosome 1p31.1 Including only the Neuronal Growth
Regulator 1 Gene in Two Siblings.
AB - We present two siblings with a partial deletion of chromosome 1p31.1 involving
only the neuronal growth regulator 1 (NEGR1) gene. The siblings had a history of
neuropsychiatric and behavioral problems, learning difficulties, hypotonia, mild
aortic root dilatation, hypermobility, and scoliosis. This is the first clinical
report of a microdeletion of chromosome 1p31.1 involving only the NEGR1 gene.
PMID- 27617113
TI - Novel Mutation in the CASR Gene (p.Leu123Ser) in a Case of Autosomal Dominant
Hypocalcemia.
AB - Autosomal dominant hypocalcemia, caused by activating mutations of the calcium
sensing receptor (CASR) gene, is characterized by hypocalcemia with an
inappropriately low concentration of parathyroid hormone (PTH). In this report,
we describe the identification of a novel missense mutation in the CASR gene, in
a boy with autosomal dominant hypocalcemia. Polymerase chain reaction (PCR)
single strand and DNA sequencing revealed a heterozygous mutation in CASR gene
that causes a leucine substitution for serine at codon 123 (p.Leu123Ser). This
mutation was absent in DNA from 50 control patients. In silico studies suggest
that the identified variant was likely pathogenic. Sequencing analysis in the
mother suggested mosaicism for the same variant, and she was clinically and
biochemically unaffected. Clinical manifestations of the index case started with
seizures at 14 months of age; cognitive impairment and several neuropsychological
disabilities were noted during childhood. Extrapyramidal signs and basal ganglia
calcification developed later, namely, hand tremor and rigidity at the age of 7
and 18 years, respectively. Laboratory analysis revealed hypocalcemia,
hyperphosphatemia, and low-serum PTH with hypomagnesemia and mild hypercalciuria.
After 2 years of treatment with calcium supplements and calcitriol, some brief
periods of clinical improvement were reported; as well as an absence of
nephrocalcinosis.
PMID- 27617114
TI - A Case of the 7p22.2 Microduplication: Refinement of the Critical Chromosome
Region for 7p22 Duplication Syndrome.
AB - We report a 14-year-old Hispanic male with a microduplication of the chromosome
7p22.2 band detected through microarray analysis. He had a history of
developmental delay and mild intellectual disability, asthma, myopia,
proportionate short stature, dysmorphic features, and Achilles tendon release.
This appears to be the first report of a patient with a microduplication of only
the chromosome 7p22.2 band and is now the smallest reported duplication to date
to include features in common with the chromosome 7p22 duplication syndrome.
PMID- 27617115
TI - Contributing Reviewers in 2014.
PMID- 27617116
TI - Identifying Human Teratogens: An Update.
PMID- 27617117
TI - Update on the Teratogenicity of Maternal Mycophenolate Mofetil.
AB - Mycophenolic acid (MPA) products, namely mycophenolate mofetil and mycophenolate
sodium, are immunosuppressive medications used to prevent rejection in solid
organ transplant recipients and to treat various autoimmune disorders.
Mycophenolate therapy is considered to be teratogenic based on observational
studies of pregnancies exposed to MPA, which demonstrated an increased incidence
of miscarriages in pregnancies exposed to MPA during their first trimester and a
pattern of birth defects in the offspring of some pregnancies exposed to MPA.
Herein, we have detailed case and series reports in a comprehensive literature
review summarizing what is known to date regarding fetal exposure to MPA. Based
on evidence from the literature, results of postmarketing surveillance, and
information from registries such as the National Transplantation Pregnancy
Registry in the United States, it is advised that pregnancy be avoided by women
taking MPA. Preconception planning offers the opportunity to explore the
alternatives to protect the mother, her transplanted organ, and minimize fetal
risk. How to proceed in cases of unplanned pregnancies exposed to MPA in
transplant recipients is a complex issue. Research involving large
epidemiological studies is expected to be sparse as women heed the warnings about
becoming pregnant on MPA. Published recommendations for managing MPA in women of
childbearing potential include discontinuing the medication prior to conception,
switching the MPA to another medication, or discontinuing the MPA when the
pregnancy is discovered.
PMID- 27617119
TI - Selective Serotonin Reuptake Inhibitor Use during Pregnancy and the Risk of
Autism Spectrum Disorders: A Review.
AB - Antidepressants are widely used during pregnancy. Several studies have shown that
the use of antidepressants during pregnancy is linked to adverse outcomes,
including congenital malformations, prematurity, and low birth weight. However,
there is a knowledge gap regarding the potential association between gestational
exposure to antidepressants and the risk of autism spectrum disorders (ASD). The
etiology of ASD remains unclear, although studies have implicated genetic
predispositions and environmental risk factors in the development of ASD in
children. In this review, we describe the association between gestational use of
antidepressants, specifically selective serotonin reuptake inhibitors, and the
risk of ASD.
PMID- 27617118
TI - Update on Prepregnancy Maternal Obesity: Birth Defects and Childhood Outcomes.
AB - Obesity is a growing global health epidemic. It is estimated that more than 20%
of pregnancies are complicated by obesity. Prepregnancy obesity has been
associated with birth defects such as neural tube defects, macrosomia, fetal
death, and long-term effects such as asthma on the offspring. We provide a
summary of the most recent studies and meta-analyses on obesity and birth
outcome. Possible mechanisms of actions are explored and recommendations for
further research are highlighted.
PMID- 27617122
TI - Genetic Advances in Intellectual Disability.
PMID- 27617120
TI - An Update on Maternal Use of Antiepileptic Medications in Pregnancy and
Neurodevelopment Outcomes.
AB - Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age.
In utero exposure to some AEDs can have significant cognitive and behavioral
consequences for the unborn child. Recently, prospective studies of women taking
AEDs during pregnancy have added significantly to our understanding of cognitive
and behavioral teratogenic risks posed by fetal AED exposure. Valproate is
clearly associated with impaired cognitive development as well as an increased
risk of disorders such as autism and autism spectrum disorder. Exposure to
carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated
with more favorable cognitive and behavioral outcomes than valproate, but more
data are required to clarify if these AEDs have more subtle effects on cognition
and behavior. There are insufficient data on the developmental effects of other
AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are
poorly understood, including the genetic factors that affect susceptibility to
AEDs.
PMID- 27617121
TI - Maternal Iron Status in Pregnancy and Long-Term Health Outcomes in the Offspring.
AB - Iron is an essential micronutrient and is important not only in carrying oxygen
but also to the catalytic activity of a variety of enzymes. In the fetus, it is
vital to the synthesis of hemoglobin and in brain development. Iron deficiency
(ID) anemia in pregnancy is a common problem, even in high-income country
settings. Around 50% of pregnant women worldwide are anemic, with at least half
of this burden due to ID. Iron supplements are widely recommended and used during
pregnancy globally. However, the evidence on the extent of benefit they
contribute to the offspring's health is not well established, and their routine
use has its side effects and drawbacks. Dietary iron intake is difficult to
assess accurately and it is unlikely to be sufficient to meet the demands of
pregnancy if women start with inadequate body iron stores at conception. Evidence
from experimental animal models suggests that maternal ID during pregnancy is
associated with fetal growth restriction, as well as offspring obesity and high
blood pressure later in life. The possible biological mechanisms for this
observed association may be due to ID-induced changes in placental structure and
function, enzyme expression, nutrient absorption, and fetal organ development.
However, such evidence is limited in human studies. Prenatal ID in experimental
animal models also adversely affected the developing brain structures,
neurotransmitter systems, and myelination resulting in acute brain dysfunction
during the period of deficiency and persistence of various postnatal
neurobehavioral abnormalities as well as persistent dysregulation of some genes
into adult life after iron repletion pointing to the possibility of gene
expression changes. The evidence from human population studies is limited and
heterogeneous and more research is needed in the future, investigating the
effects of ID in pregnancy on future offspring health outcomes.
PMID- 27617124
TI - Overgrowth Syndromes.
AB - Numerous multiple malformation syndromes associated with pathologic overgrowth
have been described and, for many, their molecular bases elucidated. This review
describes the characteristic features of these overgrowth syndromes, as well as
the current understanding of their molecular bases, intellectual outcomes, and
cancer predispositions. We review syndromes such as Sotos, Malan, Marshall-Smith,
Weaver, Simpson-Golabi-Behmel, Perlman, Bannayan-Riley-Ruvalcaba, PI3K-related,
Proteus, Beckwith-Wiedemann, fibrous dysplasia, Klippel-Trenaunay-Weber, and
Maffucci.
PMID- 27617123
TI - Next-Generation Sequencing in Intellectual Disability.
AB - Next-generation sequencing technologies have revolutionized gene discovery in
patients with intellectual disability (ID) and led to an unprecedented expansion
in the number of genes implicated in this disorder. We discuss the strategies
that have been used to identify these novel genes for both syndromic and
nonsyndromic ID and highlight the phenotypic and genetic heterogeneity that
underpin this condition. Finally, we discuss the future of defining the genetic
etiology of ID, including the role of whole-genome sequencing, mosaicism, and the
importance of diagnostic testing in ID.
PMID- 27617125
TI - Neurocutaneous Manifestations of Genetic Mosaicism.
AB - Genetic mosaicism is defined as the presence of two or more genetically distinct
cell populations in a single individual. Ever more disorders are found to be
manifestations of mosaicism and together constitute a significant proportion of
the morbidity confronting pediatric specialists. An emerging category is that of
overgrowth syndromes with skin manifestations and neurological or developmental
abnormalities, such as the well-known Proteus syndrome. In recent years, we have
seen dramatic advances in our understanding of these disorders and we now know
the genetic basis of many of them. This has profound consequences for diagnosis,
counselling, and even treatment, with therapies targeted to specific pathways
becoming available for clinical use. Recognizing such overgrowth syndromes,
therefore, is more important than ever. Fortunately, their skin manifestations
can provide important diagnostic clues when evaluated in the entire phenotypic
context. In this review, I provide an overview of the most frequently seen mosaic
neurocutaneous phenotypes and discuss their molecular basis.
PMID- 27617126
TI - Intellectual Disability: When the Hypertrichosis Is a Clue.
AB - The skin and the central and peripheral nervous system both derive from the
ectoderm ridge. Therefore, several syndromes characterized by the presence of
intellectual disability (ID) can be associated with specific congenital cutaneous
manifestations. In this review, we list some of the most frequent diseases
characterized by the presence of ID associated with hirsutism, which might be an
incentive for the clinicians to pay attention to the ectodermal annexes in
patients with ID.
PMID- 27617127
TI - Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith-Magenis
and Potocki-Lupski Syndromes.
AB - Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal
contiguous gene syndromes within the well-characterized 17p11.2 region.
Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the
mechanistically predicted homologous recombination reciprocal of the SMS
microdeletion, both resulting in multiple congenital anomalies. Mouse model
studies have revealed that the retinoic acid-inducible 1 gene (RAI1) within the
SMS and PTLS critical genomic interval is the dosage-sensitive gene responsible
for the major phenotypic features in these disorders. Even though PTLS and SMS
share the same genomic region, clinical manifestations and behavioral issues are
distinct and in fact some mirror traits may be on opposite ends of a given
phenotypic spectrum. We describe the neurobehavioral phenotypes of SMS and PTLS
patients during different life phases as well as clinical guidelines for
diagnosis and a multidisciplinary approach once diagnosis is confirmed by array
comparative genomic hybridization or RAI1 gene sequencing. The main goal is to
increase awareness of these rare disorders because an earlier diagnosis will lead
to more timely developmental intervention and medical management which will
improve clinical outcome.
PMID- 27617128
TI - Pitt-Hopkins Syndrome and Differential Diagnosis: A Molecular and Clinical
Challenge.
AB - Pitt-Hopkins syndrome is an emerging neurodevelopmental disorder caused by
haploinsufficiency of the TCF4 gene on chromosome 18q21. It is characterized by
severe intellectual disability, seizures, microcephaly, constipation and a
distinctive facial gestalt. Although the overlapping phenotype of microcephaly,
epilepsy, absent speech and constipation represents a challenge for the
differential diagnosis with Angelman syndrome, Rett syndrome and Mowat-Wilson
syndrome, distinctive of Pitt-Hopkins syndrome are breathing abnormalities, that
can occur as either hyperventilation episodes or apnea crises, and a typical
facial dysmorphism, including bitemporal narrowing, squared forehead, deep-set
eyes, peculiar nose conformation, with broad nasal bridge, down-turned nasal tip
and flaring nostrils, typical shape of the mouth, with a tented and M shaped
upper lip, and widely spaced teeth. The occurrence of these signs in variable
association of uncoordinated movements, microcephaly of postnatal onset, eye
abnormalities, constipation, epilepsy and subtle brain abnormalities is highly
predictive of a TCF4 mutation, making it possible to plan a genetic test of
choice among severe encephalopathies. Angelman syndrome represents the
nosological condition closest to Pitt-Hopkins syndrome.
PMID- 27617130
TI - Microarray Analysis of 8p23.1 Deletion in New Patients with Atypical Phenotypical
Traits.
AB - We describe two patients carrying deletions of chromosome 8p23.1 with a commonly
critical region identified by means of oligonucleotide array comparative genomic
hybridization (array CGH). They didn't present congenital heart defects or
behavioral problems. Only one patient presented with intellectual disability and
carrying deletion of TNKS gene. We presumed the inclusion of TNKS gene in the
mental impairment.
PMID- 27617129
TI - Ultra-Rare Syndromes: The Example of Rubinstein-Taybi Syndrome.
AB - Rubinstein-Taybi syndrome (RSTS) is a rare, congenital, plurimalformative, and
neurodevelopmental disorder. Clinical diagnosis can be complicated by the
heterogeneous clinical presentation and the lack of a consensus list of
diagnostic criteria, and it is confirmed by molecular tests in approximately 55
to 78% of cases. The etiology is partially known with mutations in two
functionally related genes: CREBBP and EP300. Notwithstanding the knowledge on
clinical, genetic, and allelic heterogeneity, no clear genotype-phenotype
correlation has yet been established. Standardized guidelines for the management
of pediatric patients are available and therapy for RSTS patients is currently
only symptomatic. In this article, several clinic and genetic aspects of RSTS are
critically reviewed.
PMID- 27617131
TI - A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital
Hypothyroidism in Three Siblings Born to a Consanguineous Family.
AB - Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and
germ-line mutations in the TPO gene cause the inherited form of the disease. Our
aim in this study was to determine the genetic basis of congenital hypothyroidism
in three affected children coming from a consanguineous Turkish family. Because
CH is usually inherited in autosomal recessive manner in consanguineous/multicase
families, we adopted a two-stage strategy of genetic linkage studies and targeted
sequencing of the candidate genes. First, we investigated the potential genetic
linkage of the family to any known CH locus, using microsatellite markers, and
then screened for mutations in linked-gene by conventional sequencing. The family
showed potential linkage to the TPO gene and we detected a homozygous duplication
(c.1184_1187dup4) in all cases. The mutation segregated with disease status in
the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation
in the TPO gene and helps establish a genotype/phenotype correlation associated
with this mutation. It also highlights the importance of molecular genetic
studies in the definitive diagnosis and accurate classification of CH.
PMID- 27617132
TI - A New Case of a Complex Small Supernumerary Marker Chromosome: A
Der(9)t(7;9)(p22;q22) due to a Maternal Balanced Rearrangement.
AB - Complex small supernumerary marker chromosomes (sSMCs) constitute one of the
smallest subsets within the patients with an sSMC. Complex sSMCs consist of
chromosomal material derived from more than one chromosome, for example, the
derivative der(22)t(11;22)(q23;q11.2) in Emanuel syndrome. Here, a yet unreported
case of a complex sSMC formed due to a t(7;9)(p22;q22)mat is presented.
PMID- 27617133
TI - A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2
Deletion Syndrome.
AB - Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1
associated lissencephaly) include classic lissencephaly, microcephaly, cardiac
malformations, growth restriction, and characteristic facial changes. Individuals
with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome)
are known to have congenital cardiac malformations (in particular conotruncal
defects), palatal abnormalities (especially velopharyngeal insufficiency),
hypocalcemia, immune deficiency, learning disabilities, and characteristic facial
features. This case report describes phenotypic characteristics of a patient with
extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is
unique in the medical literature. Prognosis in this concurrent phenotype is poor
with our patient suffering from several malformations seen in both conditions and
expiring in the neonatal period.
PMID- 27617134
TI - Hepatoblastoma Associated with Trisomy 18.
AB - Very few reports exist in the literature regarding a possible association between
trisomy 18 patients and the incidence of hepatoblastoma. Fewer reports exist on
patients with multifocal hepatoblastoma. We reviewed our institutional database
for the past 10 years and found three cases with this possible association to the
tumor.
PMID- 27617135
TI - A Case of Anterior Segment Dysgenesis with Iridolenticular Adhesions in Trisomy
18.
AB - Trisomy 18 (or Edwards syndrome) has an incidence of 1 in 6,000 to 8,000 live
births, making it the second most common trisomy after trisomy 21. Ophthalmologic
anomalies include epicanthal folds, hypertelorism, and hypoplastic supraorbital
ridges, whereas corneal opacities, microcornea, congenital glaucoma, cataract,
retinal depigmentation, retinal vascular tortuosity, colobomatous microphthalmia,
and cyclopia are thought to be less common; iridolenticular adhesions have not
been previously reported. Our patient was a female with confirmed trisomy 18 with
ophthalmologic examination revealing corneal opacities and iridolenticular
adhesions. Insofar as corneal opacities are a known entity in trisomy 18 and have
been considered by some to be of clinical importance, iridolenticular adhesions
may also be a noteworthy manifestation of the disease's anterior segment
dysgenesis.
PMID- 27617136
TI - Genetic Advances in Childhood Nephrological Disorders.
PMID- 27617137
TI - Techniques and Approaches to Genetic Analyses in Nephrological Disorders.
AB - Inherited renal disease is a leading cause of morbidity and mortality in
pediatric nephrology. High throughput advancements in genomics have led to
greater understanding of the biologic underpinnings of these diseases. However,
the underlying genetic changes explain only part of the molecular biology that
contributes to disease manifestation and progression. Other omics technologies
will provide a more complete picture of these cellular processes. This review
discusses these omics technologies in the context of pediatric renal disease.
PMID- 27617138
TI - The Genetics of Nephrotic Syndrome.
AB - Nephrotic syndrome (NS) is a common pediatric kidney disease and is defined as
massive proteinuria, hypoalbuminemia, and edema. Dysfunction of the glomerular
filtration barrier, which is made up of endothelial cells, glomerular basement
membrane, and visceral epithelial cells known as podocytes, is evident in
children with NS. While most children have steroid-responsive nephrotic syndrome
(SSNS), approximately 20% have steroid-resistant nephrotic syndrome (SRNS) and
are at risk for progressive kidney dysfunction. While the cause of SSNS is still
not well understood, there has been an explosion of research into the genetic
causes of SRNS in the past 15 years. More than 30 proteins regulating the
function of the glomerular filtration barrier have been associated with SRNS
including podocyte slit diaphragm proteins, podocyte actin cytoskeletal proteins,
mitochondrial proteins, adhesion and glomerular basement membrane proteins,
transcription factors, and others. A genetic cause of SRNS can be found in
approximately 70% of infants presenting in the first 3 months of life and 50% of
infants presenting between 4 and 12 months, with much lower likelihood for older
patients. Identification of the underlying genetic etiology of SRNS is important
in children because it allows for counseling of other family members who may be
at risk, predicts risk of recurrent disease after kidney transplant, and predicts
response to immunosuppressive therapy. Correlations between genetic mutation and
clinical phenotype as well as genetic risk factors for SSNS and SRNS are reviewed
in this article.
PMID- 27617139
TI - The Genetics of Urinary Tract Infections and the Innate Defense of the Kidney and
Urinary tract.
AB - The urinary tract is a sterile organ system. Urinary tract infections (UTIs) are
common and often serious infections. Research has focused on uropathogen,
environment, and host factors leading to UTI pathogenesis. A growing body of
evidence exists implicating genetic factors that can contribute to UTI risks. In
this review, we highlight genetic variations in aspects of the innate immune
system critical to the host response to uropathogens. This overview includes
genetic variations in pattern recognition receptor molecules,
chemokines/cytokines, and neutrophil activation. We also comprehensively cover
murine knockout models of UTI, genetic variations involved in renal scarring as a
result of ascending UTIs, and asymptomatic bacteriuria.
PMID- 27617140
TI - The Genetics of Ultra-Rare Renal Disease.
AB - The complement-mediated renal diseases are a group of ultra-rare renal diseases
that disproportionately affect children and young adults and frequently lead to
irreversible renal failure. Genetic mutations in alternate pathway of complement
genes are pathomechanistically involved in a significant number of these unique
diseases. Here, we review our current understanding of the role of genetics in
the primary complement-mediated renal diseases affecting children, with a focus
on atypical hemolytic uremic syndrome and C3 glomerulopathy. Also, included is a
brief discussion of the related diseases whose relationship to complement
abnormality has been suspected but not yet confirmed. Advances in genetics have
transformed both treatment and outcomes in these historically difficult to treat,
highly morbid diseases.
PMID- 27617141
TI - Genetic Considerations in Pediatric Chronic Kidney Disease.
AB - Chronic kidney disease (CKD) in children is an irreversible process that, in some
cases, may lead to end-stage renal disease. The majority of children with CKD
have a congenital disorder of the kidney or urological tract arising from birth.
There is strong evidence for both a genetic and epigenetic component to
progression of CKD. Utilization of gene-mapping strategies, ranging from genome
wide association studies to single-nucleotide polymorphism analysis, serves to
identify potential genetic variants that may lend to disease variation. Genome
wide association studies evaluating population-based data have identified
different loci associated with CKD progression. Analysis of single-nucleotide
polymorphisms on an individual level suggests that secondary systemic sequelae of
CKD are closely related to dysfunction of the cardiovascular-inflammatory axis
and may lead to advanced cardiovascular disease through abnormal vascular
calcification and activation of the renin-angiotensin system. Similarly, genetic
variants affecting cytokine control, fibrosis, and parenchymal development may
modulate CKD through development and acceleration of renal interstitial fibrosis.
Epigenetic studies evaluate modification of the genome through DNA methylation,
histone modification, or RNA interference, which may be directly influenced by
external or environmental factors directing genomic expression. Lastly, improved
understanding of the genetic and epigenetic contribution to CKD progression may
allow providers to identify a population at accelerated risk for disease
progression and apply novel therapies targeted at the genetic mechanism of
disease.
PMID- 27617142
TI - Developmental Genetics and Congenital Anomalies of the Kidney and Urinary Tract.
AB - Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth
defects and the leading cause of end-stage renal disease in children. There is a
wide spectrum of renal abnormalities, from mild hydronephrosis to more severe
cases, such as bilateral renal dysplasia. The etiology of the majority of cases
of CAKUT remains unknown, but there is increasing evidence that genomic imbalance
contributes to the pathogenesis of CAKUT. Advances in human and mouse genetics
have contributed to increased understanding of the pathophysiology of CAKUT.
Mutations in genes involved in both transcription factors and signal transduction
pathways involved in renal development are associated with CAKUT. Large cohort
studies suggest that copy number variants, genomic, or de novo mutations may
explain up to one-third of all cases of CAKUT. One of the major challenges to the
use of genetic information in the clinical setting remains the lack of strict
genotype-phenotype correlation. However, identifying genetic causes of CAKUT may
lead to improved diagnosis of extrarenal complications. With the advent of
decreasing costs for whole genome and exome sequencing, future studies focused on
genotype-phenotype correlations, gene modifiers, and animal models of gene
mutations will be needed to translate genetic advances into improved clinical
care.
PMID- 27617145
TI - Contributing Reviewers in 2015.
PMID- 27617143
TI - AKI and Genetics: Evolving Concepts in the Genetics of Acute Kidney Injury:
Implications for Pediatric AKI.
AB - In spite of recent advances in the field of acute kidney injury (AKI) research,
morbidity and mortality remain high for AKI sufferers. The study of genetic
influences in AKI pathways is an evolving field with potential for improving
outcomes through the identification of risk and protective factors at the
individual level that may in turn allow for the development of rational
therapeutic interventions. Studies of single nucleotide polymorphisms, individual
susceptibility to nephrotoxic medications, and epigenetic factors comprise a
growing body of research in this area. While promising, this field is still only
emerging, with a small number of studies in humans and very little data in
pediatric patients.
PMID- 27617146
TI - Hereditary Cancer Syndromes in Children.
PMID- 27617144
TI - Actualizing the Benefits of Genomic Discovery in Pediatric Nephrology.
AB - The discovery of genetic variation associated with pediatric kidney disease has
shed light on the biology underlying these conditions and, in some cases, has
improved our clinical management of patients. We are challenged to continue the
momentum of the genomic era in pediatric nephrology by identifying novel disease
associated genetic variation and translating these discoveries into clinical
applications. This article reviews the diverse forms of genetic architecture that
have been found to be associated with kidney diseases and traits. These include
rare, fully penetrant variants responsible for Mendelian forms of disease, copy
number variants, and more common variants associated with increased risk of
disease. These discoveries have provided us with a greater understanding of the
molecular mechanisms underlying these conditions and highlighted key pathways for
potential intervention. In a number of areas, the identification of rare, fully
penetrant variants is immediately clinically relevant, whether in regard to
diagnostic testing, prediction of outcomes, or choice of therapies and
interventions. This article discusses limitations in the deterministic view of
rare, putatively causal mutations, a challenge increasing in importance as
sequencing expands to many more genes and patients. This article also focusses on
common genetic variants, using those found to be associated with focal segmental
glomerulosclerosis in African-Americans, IgA nephropathy, chronic kidney disease
(CKD), and estimated glomerular filtration rate (eGFR) as examples. Identifying
common genetic variants associated with disease will complement other areas of
genomic inquiry, lead to a greater biological understanding of disease, and will
benefit pediatric nephrology patients.
PMID- 27617147
TI - Familial Adenomatous Polyposis.
AB - Familial adenomatous polyposis (FAP), caused by a germline mutation in the
adenomatous polyposis coli (APC) gene on chromosome 5q21, is an autosomal
dominant disorder characterized by hundreds to thousands of adenomas throughout
the gastrointestinal tract. A variety of extraintestinal manifestations,
including thyroid, soft tissue, and brain tumors, may also be present. These
patients inevitably develop colorectal carcinoma by the fourth decade of life. In
this review, the pathology, epidemiology, and genetic features of FAP are
discussed.
PMID- 27617148
TI - Li-Fraumeni Syndrome.
AB - Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a
germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal
dominant pattern of inheritance with high penetrance. These patients have a very
high lifetime cumulative risk of developing multiple malignancies and have a
strong family history of early-onset malignancies. The protein p53, encoded by
TP53, has a complex set of genome-preserving functions initiated during episodes
of cellular stress and DNA damage. In LFS, TP53 gene mutations cause the loss of
function of p53, leading to downstream events permissive for development of
various malignancies throughout life. The LFS component tumors include soft
tissue sarcomas, osteosarcoma, premenopausal breast cancer, brain tumors, and
adrenal cortical carcinomas. Multiple types of sarcomas have been reported in
association with LFS; this review article will focus on the most frequently
encountered pediatric sarcomas associated with TP53 mutations.
PMID- 27617149
TI - Multiple Endocrine Neoplasia: A Genetically Diverse Group of Familial Tumor
Syndromes.
AB - Multiple endocrine neoplasia (MEN) syndrome is a familial cancer syndrome
characterized by neuroendocrine tumors. The syndrome encompasses four major
subtypes: MEN1, MEN2A, MEN2B, and MEN4. MEN1 is caused by mutations in the MEN1
gene, MEN2A and MEN2B are caused by mutations in RET, and MEN4 is caused by
mutations in CDKNB1. All are inherited in an autosomal dominant pattern, but de
novo cases do arise. While all subtypes are associated with neuroendocrine
tumors, each has characteristic organ involvement. Identifying patients with the
syndrome can aid in proper screening and treatment.
PMID- 27617150
TI - Neurofibromatosis: A Review of NF1, NF2, and Schwannomatosis.
AB - The neurofibromatoses are a heterogeneous group of hereditary cancer syndromes
that lead to tumors of the central and peripheral nervous systems, as well as
other organ systems. By far the most common form is neurofibromatosis 1 (96%),
followed by neurofibromatosis 2 (3%), and a more recently recognized, lesser
known form, schwannomatosis. The diagnostic criteria, pathogenesis, molecular
considerations, and clinical manifestations are discussed in this review article.
PMID- 27617152
TI - Von Hippel-Lindau Disease.
AB - Von Hippel-Lindau disease is an autosomal dominant syndrome which occurs
secondary to germline mutations in the VHL tumor suppressor gene, located on
chromosome 3. Clinically von Hippel-Lindau disease is characterized by an
increased risk of developing simple visceral cysts, most commonly in the pancreas
and kidneys, in addition to an increased risk of developing neoplasms, often with
clear cell features, in a multitude of organ systems. The most common neoplasms
are cerebellar and retinal hemangioblastomas, adrenal pheochromocytomas, clear
cell renal cell carcinomas, pancreatic neuroendocrine tumors, pancreatic serous
cystadenomas, and endolymphatic sac tumors. These lesions most commonly present
during adulthood; however, screening and surveillance for the development of
these lesions should begin in the pediatric years for patients with von Hippel
Lindau disease. In this review article, the genetics and most common neoplasms of
von Hippel-Lindau disease are reviewed, with an eye towards implications for the
pediatric patient.
PMID- 27617153
TI - Rhabdoid Tumor Predisposition Syndrome and Pleuropulmonary Blastoma Syndrome.
AB - In recent years, hereditary cancer syndromes have developed greater interest in
the scientific community. Two such syndromes, rhabdoid tumor syndrome and
pleuropulmonary blastoma (DICER1) syndrome, have appeared increasingly in the
literature. This review will discuss these two syndromes in terms of clinical
parameters, associated tumors, and genetic associations.
PMID- 27617154
TI - The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of
Literature.
AB - We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23
microduplication detected by chromosomal microarray (CMA) analysis and reviewed
the literature from 18 published clinical reports. Our patient had specific
phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing
face with a short neck and over folded ears. We reviewed the published clinical,
cognitive, behavioral, and cytogenetic findings grouped by speech and language
delay, growth and development, craniofacial, clinical, and behavior and cognitive
features due to the 7q11.23 microduplication. This microduplication syndrome is
characterized by speech delay (91%), social anxiety (42%), attention deficit
hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and
separation anxiety (13%). Other findings include abnormal brain imaging (80%),
congenital heart and vascular defects (54%), and mild intellectual disability
(38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which
is due to a deletion of the same chromosome region. Both syndromes have abnormal
brain imaging, hypotonia, delayed motor development, joint laxity, mild
intellectual disability, ADHD, autism, and poor visuospatial skills but opposite
or dissimilar findings regarding speech and behavioral patterns, cardiovascular
problems, and social interaction. Those with WBS are prone to have hyperverbal
speech, lack of stranger anxiety, and supravalvular aortic stenosis while those
with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are
prone to aortic dilatation.
PMID- 27617151
TI - Syndrome-Associated Tumors by Organ System.
AB - Certain tumors suggest the possibility of a patient harboring a genetic syndrome,
particularly in children. Syndrome-associated tumors of the gastrointestinal
tract, genitourinary tract, gynecologic tract, heart, lungs, brain, eye,
endocrine organs, and hematopoietic system will be briefly discussed.
PMID- 27617155
TI - The Psychosocial Impact of Fabry Disease on Pediatric Patients.
AB - Fabry disease (FD) is a multisystemic disease that has previously been reported
to result in poorer quality of life and psychosocial functioning in impacted
adults. However, prior to the current study, limited data were available on the
impact of FD in children and adolescents. Therefore, the present study examined
the differences of quality of life, psychosocial functioning, and depression in
children with FD as compared with a healthy sample. Results indicated that
children with FD were experiencing poorer quality of life than their healthy
counterparts. Notably, results consistently identified adolescents with FD as
more heavily impacted than younger children, although not to the same degree as
adults with FD as reported in previous studies. Therefore, adolescence may be a
critical point in the development of individuals with FD during which effective
multidisciplinary interventions could be utilized to prevent poor quality of life
and psychosocial functioning in adulthood.
PMID- 27617157
TI - Thoracic Hypoplasia at Birth as Presenting Feature of Shwachman-Diamond Syndrome
in Twins.
AB - Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder of marrow
failure syndrome and exocrine pancreatic dysfunction with an estimated incidence
of 1/76,000. When present, characteristic skeletal abnormalities are strongly
suggestive of SDS but most often they are seen during childhood and adolescence.
We present a case of preterm twins with prenatal diagnosis of thoracic hypoplasia
and a clinical evolution that lead to an early diagnosis of SDS. This report
highlights the importance of a high index of suspicion for SDS in case of
neonatal thoracic hypoplasia.
PMID- 27617156
TI - Potential Role of Cortisol in Social and Memory Impairments in Individuals with
22q11.2 Deletion Syndrome.
AB - 22q11.2 Deletion syndrome is a genetic disorder characterized by physiological
and psychological symptoms. This study investigated the role of cortisol on the
social and cognitive impairments in children with 22q11.2. A total of 11 children
with 22q11.2 were assessed for baseline cortisol levels and received broad
neuropsychological testing. Results were compared with 11 controls. Children with
22q11.2 had significantly higher cortisol levels. A significant negative
correlation was observed between the general memory and attention/concentration
indices of the Wide Range Assessment of Memory and Learning, 2nd edition and
cortisol concentrations in the control population. These data provide evidence of
a possible causal mechanism that underlies social impairments in stress
disorders.
PMID- 27617158
TI - Fanconi-Bickel Syndrome: Two Pakistani Patients Presenting with Hypophosphatemic
Rickets.
AB - Fanconi-Bickel syndrome is a rare inherited disorder characterized by hepatorenal
glycogen accumulation, renal tubular dysfunction, growth failure, and impaired
utilization of glucose and galactose. We report the first two children with
Fanconi-Bickel syndrome from Pakistan who presented with classical features of
Fanconi-Bickel Syndrome. Both patients were found to be homozygous for a single
nucleotide deletion in the SLC2A2 gene defined as c.339delC. This mutation was
previously described in an Arab patient who was initially presented as permanent
neonatal diabetes mellitus before developing classical features of Fanconi-Bickel
syndrome.
PMID- 27617159
TI - An Unbalanced Rearrangement of Chromosomes 4:20 is Associated with Childhood
Osteoporosis and Reduced Caspase-3 Levels.
AB - The purpose of this study was to investigate the association of a chromosome 4:20
imbalance with osteoporosis in three related children. Bone biochemistry, bone
turnover markers, and dual-energy X-ray absorptiometry (DXA) scanning were
performed in all three cases and bone biopsy and histomorphometry in one. The
chromosome imbalance was delineated by array comparative genomic hybridization
(aCGH) and analyzed for candidate genes. A potential candidate gene within the
deleted region is caspase-3, previously linked to low bone mineral density (BMD)
in heterozygous mice thus caspase-3 activity was measured in cases and controls.
Routine bone biochemistry and markers of bone turnover did not reveal any
abnormality. DXA showed reduced total and lumbar spine bone mineral content. aCGH
showed an 8 megabase (Mb) deletion of terminal chromosome 4q incorporating a
region previously linked to low BMD and a 15 Mb duplication of terminal
chromosome 20p. Bone biopsy showed a high bone turnover state, trabecularisation
of cortical bone and numerous small osteoclasts coupled with normal bone
formation. Basal serum caspase-3 activity was lower in cases compared with
controls. We conclude that the early-onset osteoporosis with low basal levels of
caspase-3 and abnormal osteoclasts is a feature of this chromosomal
translocation. Further investigation of the role of the deleted and duplicated
genes and especially caspase-3 is required.
PMID- 27617161
TI - Comment on "Identifying Human Teratogens: An Update".
PMID- 27617160
TI - Two Novel GLDC Mutations in a Neonate with Nonketotic Hyperglycinemia.
AB - Nonketotic hyperglycinemia, also known as glycine encephalopathy (OMIM #605899),
is an autosomal recessive disorder of glycine metabolism resulting from a defect
in the glycine cleavage system. We report two novel mutations of the glycine
decarboxylase (GLDC) gene observed in a compound heterozygous state in a neonate
of mixed Maori and Caucasian parentage: c.395C>T p.(Ser132Leu) in exon 3, and
c.256-?_334+?del p.(Ser86Valfs*119), resulting in an out-of-frame deletion of
exon 2. Additionally, we describe our experience of implementing the ketogenic
diet, alongside standard pharmacological therapy, and highlight its potential
therapeutic benefit in severe nonketotic hyperglycinemia, particularly in seizure
management.
PMID- 27617162
TI - The Baetylus Theorem-the central disconnect driving consumer behavior and
investment returns in Wearable Technologies.
AB - The Wearable Technology market may increase fivefold by the end of the decade.
There is almost no academic investigation as to what drives the investment
hypothesis in wearable technologies. This paper seeks to examine this issue from
an evidence-based perspective. There is a fundamental disconnect in how consumers
view wearable sensors and how companies market them; this is called The Baetylus
Theorem where people believe (falsely) that by buying a wearable sensor they will
receive health benefit; data suggest that this is not the case. This idea is
grounded social constructs, psychological theories and marketing approaches. A
marketing proposal that fails to recognize The Baetylus Theorem and how it can be
integrated into a business offering has not optimized its competitive advantage.
More importantly, consumers should not falsely believe that purchasing a wearable
technology, improves health.
PMID- 27617164
TI - A Monte Carlo Approach to Biomedical Time Series Search.
AB - Time series subsequence matching (or signal searching) has importance in a
variety of areas in health care informatics. These areas include case-based
diagnosis and treatment as well as the discovery of trends and correlations
between data. Much of the traditional research in signal searching has focused on
high dimensional R-NN matching. However, the results of R-NN are often small and
yield minimal information gain; especially with higher dimensional data. This
paper proposes a randomized Monte Carlo sampling method to broaden search
criteria such that the query results are an accurate sampling of the complete
result set. The proposed method is shown both theoretically and empirically to
improve information gain. The number of query results are increased by several
orders of magnitude over approximate exact matching schemes and fall within a
Gaussian distribution. The proposed method also shows excellent performance as
the majority of overhead added by sampling can be mitigated through
parallelization. Experiments are run on both simulated and real-world biomedical
datasets.
PMID- 27617163
TI - Macrophage Inflammatory Protein-3 Alpha (MIP-3alpha)/CCL20 in HIV-1-Infected
Individuals.
AB - OBJECTIVE: Uncontrolled HIV infection progresses to the depletion of systemic and
mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the
concentration of MIP-3alpha in the blood and gut fluids. MIP-3alpha/CCL20 is the
only chemokine known to interact with CCR6 receptors which are expressed on
immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The
role and prognostic value of blood levels of MIP-3alpha in HIV-infected
individuals has yet to be described. METHODS: We determined the serum levels of
MIP-3alpha, and IFN-gamma, in 167 HIV-1-infected and 27 HIV-1-uninfected men
participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers
were measured using enzyme-linked immunosorbent assays (ELISA) and the cell
phenotypes using flow cytometry. RESULTS: Median serum levels of MIP-3alpha in
HIV-1-infected and uninfected men was significantly different (p<0.0001) and were
21.3 pg/mL and 6.4 pg/mL respectively. The HIV-1-infected men with CD4+ T cell
count <200 cells/MUL showed the highest median serum MIP-3alpha (23.1 pg/mL).
Serum levels of MIP-3alpha in HIV-1 infected (n=167) were negatively correlated
with absolute number of CD4+ T cell (p=0.01) and were positively correlated with
CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-gamma
(0.006). CONCLUSION: Serum levels of MIP-3alpha concomitantly increase with
plasma levels of IFN-gamma, CD38 expression on CD8+ T cells, and decreased of
absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3alpha
may be representation of locally high level of MIP-3alpha and more recruitment of
immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and
epithelial cells at the recto-colonel level may enhance sexual transmission of
HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and
AIDS.
PMID- 27617165
TI - Surgical Care Required for Populations Affected by Climate-related Natural
Disasters: A Global Estimation.
AB - BACKGROUND: Climate extremes will increase the frequency and severity of natural
disasters worldwide. Climate-related natural disasters were anticipated to
affect 375 million people in 2015, more than 50% greater than the yearly average
in the previous decade. To inform surgical assistance preparedness, we estimated
the number of surgical procedures needed. METHODS: The numbers of people
affected by climate-related disasters from 2004 to 2014 were obtained from the
Centre for Research of the Epidemiology of Disasters database. Using 5,000
procedures per 100,000 persons as the minimum, baseline estimates were
calculated. A linear regression of the number of surgical procedures performed
annually and the estimated number of surgical procedures required for climate
related natural disasters was performed. RESULTS: Approximately 140 million
people were affected by climate-related natural disasters annually requiring 7.0
million surgical procedures. The greatest need for surgical care was in the
People's Republic of China, India, and the Philippines. Linear regression
demonstrated a poor relationship between national surgical capacity and estimated
need for surgical care resulting from natural disaster, but countries with the
least surgical capacity will have the greatest need for surgical care for persons
affected by climate-related natural disasters. CONCLUSION: As climate extremes
increase the frequency and severity of natural disasters, millions will need
surgical care beyond baseline needs. Countries with insufficient surgical
capacity will have the most need for surgical care for persons affected by
climate-related natural disasters. Estimates of surgical are particularly
important for countries least equipped to meet surgical care demands given
critical human and physical resource deficiencies.
PMID- 27617166
TI - Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases
from 2015 Outbreak in Brazil.
AB - INTRODUCTION: Brazil is facing, since October of 2015, an outbreak of
microcephalic fetuses. This outbreak is correlated with the beginning of
circulation of Zika virus (ZIKV) in the country. Although it is clear that the
size of the head is diminished in these fetuses, the brain phenotype associated
with these malformations is unknown. METHODS: We collected computed tomography
images of the microcephaly cases from the region of Natal, Rio Grande do Norte,
from September 2015 to February 2016. FINDINGS: The microcephalies derived from
the current outbreak are associated with intracerebral calcifications,
malformation of the ventricular system, migratory disorders in the telencephalon
and, in a lower frequency, malformation of the cerebellum and brainstem.
DISCUSSION: The characteristics described herein are not usually found in other
types of microcephaly. We suggest that this work can be used as a guideline to
identify microcephaly cases associated to the current outbreak.
PMID- 27617167
TI - Coordinating the Provision of Health Services in Humanitarian Crises: a
Systematic Review of Suggested Models.
AB - BACKGROUND: Our objective was to identify published models of coordination
between entities funding or delivering health services in humanitarian crises,
whether the coordination took place during or after the crises. METHODS: We
included reports describing models of coordination in sufficient detail to allow
reproducibility. We also included reports describing implementation of identified
models, as case studies. We searched Medline, PubMed, EMBASE, Cochrane Central
Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health
Library. We also searched websites of relevant organizations. We followed
standard systematic review methodology. RESULTS: Our search captured 14,309
citations. The screening process identified 34 eligible papers describing five
models of coordination of delivering health services: the "Cluster Approach"
(with 16 case studies), the 4Ws "Who is Where, When, doing What" mapping tool
(with four case studies), the "Sphere Project" (with two case studies), the "5x5"
model (with one case study), and the "model of information coordination" (with
one case study). The 4Ws and the 5x5 focus on coordination of services for mental
health, the remaining models do not focus on a specific health topic. The Cluster
approach appears to be the most widely used. One case study was a mixed
implementation of the Cluster approach and the Sphere model. We identified no
model of coordination for funding of health service. CONCLUSION: This systematic
review identified five proposed coordination models that have been implemented by
entities funding or delivering health service in humanitarian crises. There is a
need to compare the effect of these different models on outcomes such as
availability of and access to health services.
PMID- 27617168
TI - Taste and Safety: Is the Exceptional Cuisine Offered by High End Restaurants
Paralleled by High Standards of Food Safety?
AB - INTRODUCTION: Restaurant guides such as the Good Food Guide Top 50 create a
hierarchy focussing on taste and sophistication. Safety is not explicitly
included. We used restaurant associated outbreaks to assess evidence for safety.
METHODS: All foodborne disease outbreaks in England reported to the national
database from 2000 to 2014 were used to compare the Top 50 restaurants (2015) to
other registered food businesses using the Public Health England (PHE) outbreak
database. Health Protection Teams were also contacted to identify any outbreaks
not reported to the national database. Among Good Food Guide Top 50 restaurants,
regression analysis estimated the association between outbreak occurrence and
position on the list. RESULTS: Four outbreaks were reported to the PHE national
outbreak database among the Top 50 giving a rate 39 times higher (95% CI 14.5
103.2) than other registered food businesses. Eight outbreaks among the 44
English restaurants in the Top 50 were identified by direct contact with local
Health Protection Teams. For every ten places higher ranked, Top 50 restaurants
were 66% more likely to have an outbreak (Odds Ratio 1.66, 95% CI 0.89-3.13).
DISCUSSION: Top 50 restaurants were substantially more likely to have had
reported outbreaks from 2000-2014 than other food premises, and there was a trend
for higher rating position to be associated with higher probability of reported
outbreaks. Our findings, that eating at some of these restaurants may pose an
increased risk to health compared to other dining out, raises the question of
whether food guides should consider aspects of food safety alongside the clearly
important complementary focus on taste and other aspects of the dining
experience.
PMID- 27617169
TI - Genetic Studies of Vibrio cholerae in South West Cameroon-A Phylogenetic Analysis
of Isolates from the 2010-2011 Epidemic.
AB - INTRODUCTION: During the cholera outbreak from 2010 to 2011 in Cameroon, 33,192
cases with 1,440 deaths (case fatality ratio 4.34%) were reported to the World
Health Organization. Of these, the South West Region reported 3,120 clinical
cases. This region is in the Equatorial Monsoon climatic subzone of Cameroon,
close to the coast, raising questions as to whether cases were linked with
development of environmental reservoirs. METHODS: In an investigation conducted
by the Laboratory for Emerging Infectious Diseases, University of Buea, toxigenic
V. cholerae O1 were isolated from diarrheal stool samples from 18 patients, with
ages ranging from <3 to 70 years. Coordinates for clinical centers at which cases
were identified were obtained using a handheld GPS, and were mapped using ArcGIS.
Antibiotic susceptibility testing was performed using the Kirby 'Bauer agar disc
diffusion method. The full genomes of these strains were sequenced with the
Illumina MiSeq platform. De novo assembly of cholera genomes and multiple
sequence alignment were carried out using the bioinformatics pipeline developed
in the Emerging Pathogens Institute laboratory at the University of Florida.
RESULTS/DISCUSSION: Genetic comparisons showed that isolates were closely
related, with pairwise p-distances ranging from 2.25 to 14.52 10-5 nt
substitutions per site, and no statistically significant correlation between the
pairwise genetic distances and the geographic distances among sampling locations.
Indeed, the phylogeny of the Cameroonian strains displays the typical star-like
topology and intermixing of strains from different locations that are
characteristic of an exponential outbreak localized around a relatively
restricted area with occasional spillover to other parts of the country, likely
mediated by direct human contact and human movement. Findings highlight the
utility of whole genome sequencing and phylogenetic analysis in understanding
transmission patterns at the local level.
PMID- 27617170
TI - Invasion Dynamics of Teratogenic Infections in Light of Rubella Control:
Implications for Zika Virus.
AB - INTRODUCTION: The greatest burden for a subset of pathogens is associated with
infection during pregnancy. Evidence for teratogenic effects of Zika Virus have
highlighted the importance of understanding the epidemiology of such pathogens.
Rubella is perhaps the most classic example, and there is much to be learned from
the long history of modelling associated with this virus. METHODS: We extended an
existing framework for modeling age-specific dynamics of rubella to illustrate
how the body of knowledge of rubella dynamics informs the dynamics of teratogenic
infections more broadly, and particularly the impact of control on such
infections in different transmission settings. RESULTS: During invasion, the
burden in women of childbearing age is expected to peak, but then fall to low
levels before eventually levelling out. Importantly, as illustrated by rubella
dynamics, there is potential for a paradoxical effect, where inadequate control
efforts can increase the burden. CONCLUSIONS: Drawing on the existing body of
work on rubella dynamics highlights key knowledge gaps for understanding the
risks associated with Zika Virus. The magnitude and impacts of sterilizing
immunity, plus antigenic maps measuring cross-protection with other flaviviruses,
and the magnitude of transmission, as well as likely impact of control efforts on
transmission are likely to be key variables for robust inference into the outcome
of management efforts for Zika Virus.
PMID- 27617172
TI - The role of adipose-derived inflammatory cytokines in type 1 diabetes.
AB - Adipose tissue dysfunction correlates with the development of diabetes. Mice with
an adipocyte-specific deletion of the SUMO-specific protease SENP1 develop
symptoms of type-1 diabetes mellitus (T1DM). Peri-pancreatic adipocytes (PATs)
exert both systemic and paracrine effects on pancreases function. Our recent
studies report that PATs of SENP1-deficient mice have increased proinflammatory
cytokine production compared with other adipose depots. Proinflammatory cytokines
produced from PATs not only have direct cytotoxic effects on pancreatic islets,
but also increase CCL5 expression in adjacent pancreatic islets, which induces
persistent inflammation in pancreases by acquisition of Th1 and Th17 effector T
cell subsets. Small ubiquitin-like modifier (SUMO) can post-translationally
conjugate to cellular proteins (SUMOylation) and modulate their biological
functions. Several components in SUMOylation associate with T1DM susceptibility.
We find that SUMOylation of NF-kappaB essential molecule NEMO augments NF-kappaB
activity, NF-kappaB-dependent cytokine production and pancreatic inflammation. NF
kappaB inhibitor should provide therapeutic approach to block PAT inflammation
and ameliorate the T1DM phenotype. We further propose that adipocytes in PATs may
play a primary role in establishing pancreatic immune regulation at onset of
diabetes, providing new insights into the molecular pathogenesis of type 1
diabetes.
PMID- 27617173
TI - Adipocytes, like their progenitors, contribute to inflammation of adipose tissues
through promotion of Th-17 cells and activation of monocytes, in obese subjects.
AB - Recently, we have reported that adipose tissue-derived stem cells (ASC) harvested
from obese donors induce a pro-inflammatory environment when co-cultured with
peripheral blood mononuclear cells (MNC), with a polarization of T cells toward
the Th17 cell lineage, increased secretion of IL-1beta and IL-6 pro-inflammatory
cytokines, and down-regulation of Th1 cytokines, such as IFNgamma and TNFalpha.
However, whether differentiated adipocytes, like the aforementioned ASC, are pro
inflammatory in obese subject AT remained to be investigated. Herein, we isolated
ASC from AT of obese donors and differentiated them into adipocytes, for either 8
or 14 d. We analyzed their capacity to activate blood MNC after stimulation with
phytohemagglutinin A (PHA), or not, in co-culture assays. Our results showed that
co-cultures of MNC with adipocytes, like with ASC, increased IL-17A, IL-1beta,
and IL-6 pro-inflammatory cytokine secretion. Moreover, like ASC, adipocytes down
regulated TNFalpha secretion by Th1 cells. As adipocytes differentiated from ASC
of lean donors also promoted IL-17A secretion by MNC, an experimental model of
high-fat versus chow diet mice was used and supported that adipocytes from obese,
but not lean AT, are able to mediate IL-17A secretion by PHA-activated MNCs. In
conclusion, our results suggest that, as ASC, adipocytes in obese AT might
contribute to the establishment of a low-grade chronic inflammation state.
PMID- 27617171
TI - Inside out: Bone marrow adipose tissue as a source of circulating adiponectin.
AB - The adipocyte-derived hormone adiponectin mediates beneficial cardiometabolic
effects, and hypoadiponectinemia is a biomarker for increased metabolic and
cardiovascular risk. Indeed, circulating adiponectin decreases in obesity and
insulin-resistance, likely because of impaired production from white adipose
tissue (WAT). Conversely, lean states such as caloric restriction (CR) are
characterized by hyperadiponectinemia, even without increased adiponectin
production from WAT. The reasons underlying this paradox have remained elusive,
but our recent research suggests that CR-associated hyperadiponectinemia derives
from an unexpected source: bone marrow adipose tissue (MAT). Herein, we elaborate
on this surprising discovery, including further discussion of potential
mechanisms influencing adiponectin production from MAT; additional evidence both
for and against our conclusions; and observations suggesting that the
relationship between MAT and adiponectin might extend beyond CR. While many
questions remain, the burgeoning study of MAT promises to reveal further key
insights into MAT biology, both as a source of adiponectin and beyond.
PMID- 27617174
TI - Regulation of human adipogenesis by miR125b-5p.
AB - MicroRNAs (miRNAs) are non-coding RNAs that regulate target gene expression at
the post-transcriptional level and are supposed to be implicated in the control
of adipogenesis. We aimed to identify miRNAs which are involved in the regulation
of human adipogenesis and searched for their molecular targets. Applying
microarray-analysis we identified miR125b-5p as upregulated during human
adipocyte differentiation, although its role during adipogenesis is unknown. We
identified and characterized the matrix metalloproteinase 11 (MMP11) as a direct
target of miR125b-5p by showing that miR125b-5p overexpression significantly
reduces MMP11 luciferase activity and mutation of any single binding site was
sufficient to abolish the miR125b-5p mediated inhibition of luciferase activity.
MMP11 overexpression decreased fat accumulation, indicating that MMP11 acts as an
anti-adipogenic regulator. In contrast, overexpression of miR125b-5p itself
reduced adipogenesis. In summary, we identified miR125b-5p as upregulated during
human adipogenesis indicating that miR125b-5p may serve as a regulator of human
adipocyte differentiation. We further show that miR125b-5p downregulates the anti
adipogenic MMP11, but directly inhibits adipogenesis itself. Taken together,
these data implicate that miR125b-5p can affect human adipogenesis via MMP11 and
probably additional targets.
PMID- 27617175
TI - HSD1 and AQP7 short-term gene regulation by cortisone in 3T3-L1 adipocytes.
AB - Adipose Tissue (AT) is a complex organ with a crucial regulatory role in energy
metabolism and in the development of obesity and the Metabolic Syndrome (MS).
Modified responses and the metabolism of hormones have been observed in visceral
adiposity during obesity, specifically as related with cortisone. The objective
of this study was to assess, in the 3T3-L1 adipocyte cell line, the short-term
effect of cortisone on the expression of 11beta-Hydroxysteroid dehydrogenase 1
(Hsd1), which is responsible for activation of cortisone into cortisol, and for
Aquaporin 7 (Aqp7), involved in glycerol transport through the cell membrane.
Total RNA (tRNA) and complementary DNA (cDNA) were obtained from cell samples
treated with cortisone (0.1, 1, and 10 MUM) during different times (0, 5, 10, 15,
and 20 min, and 48 h) to quantify the expression of the aforementioned genes by
real time PCR employing MnSOD and Ppia as housekeeping genes. There was a time
dependent response of Aqp7, a dose-dependent response of Hsd1, and an increase
observed in the expression of both genes during min 1 of treatment (5- and 6
fold, respectively), followed by a decrease during the following 5-10 min (P <
0.05). With the 1-MUM cortisone treatment, both genes showed cubic tendencies in
their expression; the Hsd1 tendency is described by the equation y = 0.18*(3)
1.65*(2)+3.59x+1.31, while the Aqp7 tendency is described by y = 0.33*(3)
2.67*(2)+4.93x+1.84. There are immediate and quantitatively important actions of
cortisone on the expression of Aqp7 and Hsd1 in 3T3-L1 adipocytes.
PMID- 27617176
TI - ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation
and cardiac dysfunction in obesity.
AB - Obesity is characterized by an excessive fat accumulation in adipose tissues
leading to weight gain and is increasing in prevalence and is strongly associated
with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS)
has emerged as a key pathogenic mechanism for these disorders; activated RAS and
angiotensin (Ang) II production results in worsening of cardiovascular diseases
and angiotensin converting enzyme 2 (ACE2) negatively regulates RAS by
metabolizing Ang II into Ang 1-7. ACE2 is expressed in the adipocytes and its
expression is upregulated in response to high fat diet induced obesity in mice.
Loss of ACE2 results in heart failure with preserved ejection fraction which is
mediated in part by epicardial adipose tissue inflammation. Angiotensin 1-7
reduces the obesity associated cardiac dysfunction predominantly via its role in
adiponectin expression and attenuation of epicardial adipose tissue inflammation.
Human heart disease is also linked with inflammed epicardial adipose tissue.
Here, we discuss the important interpretation of the novel of ACE2/Ang 1-7
pathway in obesity associated cardiac dysfunction.
PMID- 27617177
TI - Minor differences in the molecular machinery mediating regulated membrane fusion
has major impact on metabolic health.
AB - The exocytosis of signaling molecules from neuronal, neuroendocrine and endocrine
cells is regulated by membrane fusion involving SNAP-25 and associated SNARE
proteins. The importance of this process for metabolic control recently became
evident by studies of mouse mutants genetically engineered to only express one of
2 closely related, alternatively-spliced variants of SNAP-25. The results showed
that even minor differences in the function of proteins regulating exocytosis are
sufficient to provoke metabolic disease, including hyperglycaemia, liver
steatosis, adipocyte hypertrophy and obesity. Thus, an imbalance in the dynamics
of hormonal and/or neurotransmitter release can cause obesity and type 2
diabetes. This recent discovery highlights the fact that metabolic health
requires a perfectly operating interplay between the SNARE protein machinery in
excitable cells and the organs responding to these messengers.
PMID- 27617179
TI - In this issue of Adipocyte.
PMID- 27617178
TI - Dropping in on the lipid droplet- tumor protein D52 (TPD52) as a new regulator
and resident protein.
AB - Lipid droplets are essential for both the storage and retrieval of excess
cellular nutrients, and their biology is regulated by a diverse range of cellular
proteins, some of which function at the lipid droplet. Numerous studies have
characterized lipid droplet proteomes in different organisms and cell types, and
RNAi whole genome screening studies have examined the genetic regulation of lipid
storage in C. elegans and D. melanogaster. While tumor protein D52 (TPD52) did
not emerge from earlier studies as a strong candidate, exogenous expression of
human TPD52 in cultured cells resulted in significantly increased numbers of
lipid droplets, and oleic acid supplementation increased TPD52 detection at both
lipid droplets and the Golgi apparatus. These results suggest that direct testing
of proteins that are infrequently but recurrently identified in proteomic and
RNAi screening studies may identify novel lipid droplet regulators. While the
analysis of these possibly lower-abundance or itinerant lipid droplet proteins
may be more technically challenging, such proteins could facilitate a more
detailed interrogation of emerging aspects of lipid droplet biology.
PMID- 27617180
TI - Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light
Adapted Human Eye.
AB - PURPOSE: To demonstrate that silent substitution stimuli can be used to generate
electroretinograms (ERGs) that effectively isolate rod photoreceptor function in
humans without the need for dark adaptation, and that this approach constitutes a
viable alternative to current clinical standard testing protocols. METHODS: Rod
isolating and non-isolating sinusoidal flicker stimuli were generated on a 4
primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from
participants with normal and compromised rod function who had not undergone dark
adaptation. Responses were subjected to Fourier analysis, and the amplitude and
phase of the fundamental were used to examine temporal frequency and retinal
illuminance response characteristics. RESULTS: Electroretinograms elicited by rod
isolating silent substitution stimuli exhibit low-pass temporal frequency
response characteristics with an upper response limit of 30 Hz. Responses are
optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There
is a significant correlation between the response amplitudes obtained with the
silent substitution method and current standard clinical protocols. Analysis of
signal-to-noise ratios reveals significant differences between subjects with
normal and compromised rod function. CONCLUSIONS: Silent substitution provides an
effective method for the isolation of human rod photoreceptor function in
subjects with normal as well as compromised rod function when stimuli are used
within appropriate parameter ranges. TRANSLATIONAL RELEVANCE: This method of
generating rod-mediated ERGs can be achieved without time-consuming periods of
dark adaptation, provides improved isolation of rod- from cone-based activity,
and will lead to the development of faster clinical electrophysiologic testing
protocols with improved selectivity.
PMID- 27617181
TI - Feasibility, Accuracy, and Repeatability of Suprathreshold Saccadic Vector
Optokinetic Perimetry.
AB - PURPOSE: To evaluate feasibility, accuracy, and repeatability of suprathreshold
Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field
Analyzer (HFA) perimetry. METHODS: The subjects included children with suspected
field defects (n = 10, age 5-15 years), adults with field defects (n = 33, age 39
78 years), healthy children (n = 12, age 6-14 years), and healthy adults (n = 30,
age 16-61 years). The test protocol comprised repeat suprathreshold SVOP and HFA
testing with the C-40 test pattern. Feasibility was assessed by protocol
completeness. Sensitivity, specificity, and accuracy of SVOP was established by
comparison with reliable HFA tests in two ways: (1) visual field pattern results
(normal/abnormal), and (2) individual test point outcomes (seen/unseen).
Repeatability of each test type was assessed using Cohen's kappa coefficient.
RESULTS: Of subjects, 82% completed a full protocol. Poor reliability of HFA
testing in child patients limited the robustness of comparisons in this group.
Sensitivity, specificity, and accuracy across all groups when analyzing the
visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was
69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points.
Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87
and 0.88, respectively) when assessing visual field pattern results, and
substantial (0.62 and 0.74, respectively) when assessing test point outcomes.
CONCLUSIONS: SVOP was accurate in this group of adults. Further studies are
required to assess SVOP in child patient groups. TRANSLATIONAL RELEVANCE: SVOP
technology is still in its infancy but is used in a number of centers. It will
undergo iterative improvements and this study provides a benchmark for future
iterations.
PMID- 27617182
TI - Retinal Arterioles in Hypo-, Normo-, and Hypertensive Subjects Measured Using
Adaptive Optics.
AB - PURPOSE: Small artery and arteriolar walls thicken due to elevated blood
pressure. Vascular wall thickness show a correlation with hypertensive subject
history and risk for stroke and cardiovascular events. METHODS: The inner and
outer diameter of retinal arterioles from less than 10 to over 150 MUm were
measured using a multiply scattered light adaptive optics scanning laser
ophthalmoscope (AOSLO). These measurements were made on three populations, one
with habitual blood pressures less than 100/70 mm Hg, one with normal blood
pressures without medication, and one with managed essential hypertension.
RESULTS: The wall to lumen ratio was largest for the smallest arterioles for all
three populations. Data from the hypotensive group had a linear relationship
between outer and inner diameters (r2 = 0.99) suggesting a similar wall structure
in individuals prior to elevated blood pressures. Hypertensive subjects fell
below the 95% confidence limits for the hypotensive relationship and had larger
wall to lumen ratios and the normotensive group results fell between the other
two groups. CONCLUSION: High-resolution retinal imaging of subjects with
essential hypertension showed a significant decrease in vessel inner diameter for
a given outer diameter, and increases in wall to lumen ratio and wall cross
sectional areas over the entire range of vessel diameters and suggests that
correcting for vessel size may improve the ability to identify significant
vascular changes. TRANSLATIONAL RELEVANCE: High-resolution imaging allows precise
measurement of vasculature and by comparing results across risk populations may
allow improved identification of individuals undergoing hypertensive arterial
wall remodeling.
PMID- 27617183
TI - Self-distancing Buffers High Trait Anxious Pediatric Cancer Caregivers against
Short- and Longer-term Distress.
AB - Pediatric cancer caregivers are typically present at their child's frequent,
invasive treatments, and such treatments elicit substantial distress. Yet,
variability exists in how even the most anxious caregivers cope. Here we examined
one potential source of this variability: caregivers' tendencies to self-distance
when reflecting on their feelings surrounding their child's treatments. We
measured caregivers' self-distancing and trait anxiety at baseline, anticipatory
anxiety during their child's treatment procedures, and psychological distress and
avoidance three months later. Self-distancing buffered high (but not low) trait
anxious caregivers against short- and long-term distress without promoting
avoidance. These findings held when controlling for other buffers, highlighting
the unique benefits of self-distancing. These results identify a coping process
that buffers vulnerable caregivers against a chronic life stressor while also
demonstrating the ecological validly of laboratory research on self-distancing.
Future research is needed to explicate causality and the cognitive and
physiological processes that mediate these results.
PMID- 27617185
TI - HRTEM low dose: the unfold of the morphed graphene, from amorphous carbon to
morphed graphenes.
AB - We present experimental evidence under low-dose conditions transmission electron
microscopy for the unfolding of the evolving changes in carbon soot during
mechanical milling. The milled soot shows evolving changes as a function of the
milling severity or time. Those changes are responsible for the transformation
from amorphous carbon to graphenes, graphitic carbon, and highly ordered
structures such as morphed graphenes, namely Rh6 and Rh6-II. The morphed
graphenes are corrugated layers of carbon with cross-linked covalently nature and
sp2- or sp3-type allotropes. Electron microscopy and numerical simulations are
excellent complementary tools to identify those phases. Furthermore, the TEAM 05
microscope is an outstanding tool to resolve the microstructure and prevent any
damage to the sample. Other characterization techniques such as XRD, Raman, and
XPS fade to convey a true identification of those phases because the samples are
usually blends or mixes of the mentioned phases.
PMID- 27617184
TI - Unlocking dimensions of social capital in the prison setting.
AB - BACKGROUND: Social capital has been shown to be a valuable resource for improving
health outcomes. However, it has received little attention in the prison setting.
Dimensions of social capital in mainstream society are likely to function
differently among inmates in prison. This study seeks to identify and understand
social capital dimensions among incarcerated men living with hepatitis C.
METHODS: In-depth interviews were conducted across three correctional centres in
New South Wales with 30 male inmates living with hepatitis C. Interviews were
transcribed then thematically coded and analysed. RESULTS: There were differences
in the access and utility of social capital dimensions in prison focusing
specifically on trust and safety, informal and formal networks, agency, and civic
engagement. CONCLUSIONS: Dimensions of social capital do not necessarily
translate into prison. An inmate's social capital may foster greater treatment
uptake relating to health and rehabilitative programs during their incarceration.
PMID- 27617186
TI - Progress and prospects of reactive oxygen species in metal carcinogenesis.
AB - Carcinogenesis induced by environmental metal exposure is a major public health
concern. The exact mechanisms underlying metal carcinogenesis remain elusive. In
the past few decades, the relationship between metal induced generation of
reactive oxygen species (ROS) and the mechanism of metal carcinogenesis has been
established. The carcinogenic process is a very complex one. In the early stage
of metal carcinogenesis or cell transformation high levels of ROS are oncogenic
by causing DNA damage, genetic instability, epigenetic alteration, and metabolic
reprogramming, leading to malignant transformation. In the second stage of metal
carcinogenesis or the cancer development of metal-transformed cells, low levels
of ROS are carcinogenic by promoting apoptosis resistance. The metal-transformed
cells have the property of autophagy deficiency, resulting in accumulation of p62
and constitutive activation of Nrf2, and leading to higher levels of
antioxidants, decreased levels of ROS, apoptosis resistance, inflammation, and
angiogenesis. This review summarizes the most recent development in the field of
metal carcinogenesis with emphasis on the difference in cellular events between
early (cell transformation) and late (after cell transformation) stages of metal
carcinogenesis.
PMID- 27617189
TI - Zika virus: A call to action for physicians in the era of climate change.
AB - In February 2016, the World Health Organization declared the mosquito-borne Zika
virus to be a "public health emergency of international concern" as the disease
linked to thousands of birth defects in Brazil spreads rapidly. The distribution
of the Aedes mosquitos has drastically increased over the past few decades, which
have been the hottest decades on Earth in more than 1000 years based on climate
proxy measures. Although a combination of factors explains the current Zika virus
outbreak, it's highly likely that the changes in the climate contribute to the
spread of Aedes vector carrying the Zika virus, the pathogen causing serious
birth defects. Physicians, both individually and collectively, as trusted and
educated members of society have critical roles to play. In addition to clinical
management and prevention of Zika, physicians should communicate about the health
benefits of addressing climate change in straightforward evidence-based language
to their local communities and policymakers, and make clear their support for
policies mitigating climate change.
PMID- 27617187
TI - Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration
(Dupuytren's Disease).
AB - Dupuytren's disease is a connective tissue disorder of the hand causing excessive
palmar fascial fibrosis with associated finger contracture and disability. The
aetiology of the disease is heterogeneous, with both genetic and environmental
components. The connective tissue is abnormally infiltrated by myofibroblasts
that deposit collagen and other extracellular matrix proteins. We describe the
clinical profile of Dupuytren's disease along with current therapeutic schemes.
Recent findings on molecular and cellular parameters that are dysregulated in
Dupuytren's disease, which may contribute to the onset of the disease, and the
role of resident inflammation promoting fibrosis, are highlighted. We review
recent literature focusing on non-myofibroblast cell types (stem cell-like
cells), their pro-inflammatory and pro-fibrotic role that may account for
abnormal wound healing response.
PMID- 27617188
TI - Strategies and First Advances in the Development of Prevascularized Bone
Implants.
AB - Despite the great regenerative potential of human bone, large bone defects are a
serious condition. Commonly, large defects are caused by trauma, bone disease,
malignant tumor removal, and infection or medication-related osteonecrosis. Large
defects necessitate clinical treatment in the form of autologous bone
transplantation or implantation of biomaterials as well as the application of
other available methods that enhance bone defect repair. The development and
application of prevascularized bone implants are closely related to the
development animal models and require dedicated methods in order to reliably
predict possible clinical outcomes and the efficacy of implants. Cell sheet
engineering, 3D-printing, arteriovenous loops, and naturally derived
decellularized scaffolds and their respective testings in animal models are
presented as alternative to the autologous bone graft in this article.
PMID- 27617191
TI - Support or competition? How online social networks increase physical activity: A
randomized controlled trial.
AB - To identify what features of online social networks can increase physical
activity, we conducted a 4-arm randomized controlled trial in 2014 in
Philadelphia, PA. Students (n = 790, mean age = 25.2) at an university were
randomly assigned to one of four conditions composed of either supportive or
competitive relationships and either with individual or team incentives for
attending exercise classes. The social comparison condition placed participants
into 6-person competitive networks with individual incentives. The social support
condition placed participants into 6-person teams with team incentives. The
combined condition with both supportive and competitive relationships placed
participants into 6-person teams, where participants could compare their team's
performance to 5 other teams' performances. The control condition only allowed
participants to attend classes with individual incentives. Rewards were based on
the total number of classes attended by an individual, or the average number of
classes attended by the members of a team. The outcome was the number of classes
that participants attended. Data were analyzed using multilevel models in 2014.
The mean attendance numbers per week were 35.7, 38.5, 20.3, and 16.8 in the
social comparison, the combined, the control, and the social support conditions.
Attendance numbers were 90% higher in the social comparison and the combined
conditions (mean = 1.9, SE = 0.2) in contrast to the two conditions without
comparison (mean = 1.0, SE = 0.2) (p = 0.003). Social comparison was more
effective for increasing physical activity than social support and its effects
did not depend on individual or team incentives.
PMID- 27617192
TI - Using photographic interpretation to evaluate the safety of home environments.
AB - In the US there were 400,000 home fires resulting in 2755 deaths, 12,450
injuries, and $6.9B lost. The purpose of this study was to evaluate the content
validity of photographs taken in the home for use as an educational instrument to
teach about "safe" and "unsafe" fire safety practice for adults and older adults.
A total of 73 home fire safety experts were provided 27 photographs to evaluate
home fire safety practice. Initially, a Krippendorff's alpha was calculated for
the first 24 questions to evaluate inter-rater reliability, and differences in
demographics were evaluated. Unique codes and themes for the last three questions
were identified and inter-rater reliability examined. A majority of respondents
were female (n = 43, 60.6%), college educated (n = 61, 83.6%), nurses (n = 25,
33.8%), or worked for a fire department (n = 21, 29.6%). Their mean age was 45.5
years and they had 11.05 years of experience. The first 24 questions had high
inter-rater reliability (Krippendorff alpha = 0.831). No significant differences
existed between the strata of the demographic variables (all p-values > 0.05).
Similarly, based on the codes and themes identified, the last three questions had
moderate-to-good inter-rater reliability (Krippendorff alpha = 0.764). Providing
photographs as a 'seek-and-find' or 'What's wrong with this picture?' tools and
simplified visual images is an excellent way to aid recognition of unsafe home
fire safety environments. Education through non-traditional visual methods
increases the possibility of change for diverse low-literacy populations.
PMID- 27617190
TI - Television viewing duration during childhood and long- association with
adolescent neuropsychological outcomes.
AB - This study is aiming to evaluate the association between television viewing
during childhood and long-term adolescent neuropsychological outcomes and the
potential explanatory pathways. This is a longitudinal study based on 278
children participating in the INMA birth cohort (1998) in Menorca Island, Spain.
The exposure is parent-reported duration of child television viewing (hours per
week) at 6 and 9 years of age. Neuropsychological outcomes were assessed at 14
years of age using the N-back test. Behavioral outcomes at 14 years of age were
assessed using the Strengths and Difficulties Questionnaire (SDQ) and school
performance was assessed by the global school score. Regression models were
developed to quantify the associations between duration of television viewing and
neuropsychological outcomes adjusted for child and parents' characteristics. The
average of weekly TV viewing from 6 to 9 years was 9.2 h (SD: 4.1). Only N-back
test outcomes exhibited statistically significant differences in crude models.
Children viewing > 14 h per week tended to show larger latencies in working
memory reaction time (HRT in ms), beta (CI) = 53 (0-107). After adjusting for
potential social confounders, the association weakened and became non-significant
but adverse trends were slightly preserved. Early life TV viewing was not
associated with adolescent neuropsychological outcomes after adjustment for
potential confounders. Further research including larger and exhaustive
population-based cohort studies is required in order to verify our conclusions.
PMID- 27617193
TI - Infant sleep problems and childhood overweight: Effects of three definitions of
sleep problems.
AB - Sleep problems have been defined using a variety of definitions. No study has
assessed the longitudinal association between infant sleep problems and childhood
overweight or obesity using existing definitions of sleep problems. This study
used longitudinal data (n = 895) from the multi-site Study of Early Child Care
and Youth Development (SECCYD) to investigate the effects of infant sleep
problems on childhood weight status in Grade 6. Infants with sleep problems in
Phase I (1991) and with complete data through Phase III (2004) of SECCYD were
included. Sleep problems were assessed using maternal reports of night wakings
and duration of a waking episode. Sleep problems were defined using Richman
(1981), Lozoff et al. (1985), and Zuckerman et al. (1987) definitions.
Multinomial logistic regression was used to examine the association between sleep
problems during infancy and childhood weight status in Grade 6 while controlling
for birth weight, race, sex, breastfeeding, maternal poverty, family structure,
and maternal education. After adjusting for all covariates, children with a
history of sleep problems were found to be overweight in Grade 6 using Zukerman
et al. (Odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.11-2.55) and
Richman (OR = 1.76; 95% CI: 1.05-2.97) definitions, but not using Lozoff et al.
DEFINITION: Infant sleep problems were not found to be associated with being
obese. The study found differential effects of infant sleep problems on childhood
overweight in Grade 6 per different definitions of sleep problems. Findings
highlight the need to construct a single definition of infant sleep problems.
PMID- 27617194
TI - Factors associated with consumption of fruits and vegetables among Community
Kitchens customers in Lima, Peru.
AB - Community Kitchens (CKs) are one of the main food providers to low-income
families in Peru and may encourage healthier diets. We aimed to determine the
prevalence of fruit and vegetable consumption and associated sociodemographic and
behavioral factors among CKs customers. A cross-sectional study enrolling
customers of 48 CKs in two areas of Lima, Peru, was performed. The self-reported
amount of fruits and vegetables consumed (< 5 vs. >= 5 servings/day) was the
outcome. The exposures were grouped in sociodemographic variables (i.e. age,
gender, education level, etc.), and self-reported intention to change eating- and
exercise-related habits in the last four weeks just prior to the interview.
Prevalence ratios (PR) were estimated using Poisson regression. Data from 422
subjects were analyzed, 328 females (77.9%), mean age 43.7 (+/- 14.5) years. Only
36 (8.5%; 95% CI 5.9%-11.2%) customers reported consuming >= 5 servings of fruits
and vegetables daily. This pattern was 4-fold more likely among those with higher
levels of education (>= 12 vs. < 7 years), and 64% less common for migrants
relative to non-migrants. In terms of intentions to change habits, those who
reported having tried to reduce sugar consumption or to eat more fruits were up
to 90% more likely to meet the >= 5 servings/day target. A substantial gap in the
consumption of >= 5 servings of fruits and vegetables/day was found among CKs
customers that does not appear to be dependent on familial income. The profiles
reported in this study can inform appropriate strategies to increase healthier
eating in this population.
PMID- 27617195
TI - Further Investigation of the Association between Anxiety Sensitivity and
Posttraumatic Stress Disorder: Examining the Influence of Emotional Avoidance.
AB - Anxiety sensitivity (AS) and the tendency to avoid emotions have both been
identified as vulnerability factors for the development and maintenance of
posttraumatic stress disorder (PTSD). Furthermore, both cross-sectional and
prospective research have provided evidence that emotional avoidance and AS
interact to predict anxiety symptoms, such that AS may only be associated with
anxiety-related pathology among those who exhibit a tendency to avoid their
emotions. The purpose of the present study was to determine if this moderator
model extends to PTSD within a sample of substance dependent patients.
Specifically, this study examined if AS is associated with PTSD only among
individuals with high (vs. low) levels of negative emotional avoidance. As
predicted, results of a logistic regression analysis revealed a significant
interaction between negative emotional avoidance and AS in predicting PTSD
status. Follow-up analyses revealed a significant positive association between AS
and PTSD status for participants high in negative emotional avoidance; however,
AS was not associated with PTSD for those low in negative emotional avoidance.
This finding remained even when relevant covariates were included in the model.
Results confirm hypotheses and are consistent with the extant anxiety-risk
literature.
PMID- 27617196
TI - The changing microbial landscape of Western society: Diet, dwellings and
discordance.
AB - BACKGROUND: The last 50-100 years has been marked by a sharp rise in so-called
"Western-diseases" in those countries that have experienced major industrial
advances and shifts towards urbanized living. These diseases include obesity,
type 2 diabetes, inflammatory bowel diseases, and food allergies in which chronic
dysregulation of metabolic and/or immune processes appear to be involved, and are
likely a byproduct of new environmental influences on our ancient genome. What we
now appreciate is that this genome consists of both human and co-evolved
microbial genes of the trillions of microbes residing in our body. Together, host
microbe interactions may be determined by the changing diets and behaviors of the
Western lifestyle, influencing the etiopathogenesis of "new-age" diseases. SCOPE
OF REVIEW: This review takes an anthropological approach to the potential
interplay of the host and its gut microbiome in the post-industrialization rise
in chronic inflammatory and metabolic diseases. The discussion highlights both
the changes in diet and the physical environment that have co-occurred with these
diseases and the latest evidence demonstrating the role of host-microbe
interactions in understanding biological responses to the changing environment.
MAJOR CONCLUSIONS: Technological advances that have led to changes in agriculture
and engineering have altered our eating and living behaviors in ways never before
possible in human history. These changes also have altered the bacterial
communities within the human body in ways that are seemingly linked with the rise
of many intestinal and systemic metabolic and inflammatory diseases. Insights
into the mechanisms of this reciprocal exchange between the environment and the
human gut microbiome may offer potential to attenuate the chronic health
conditions that derail quality of life. This article is part of a special issue
on microbiota.
PMID- 27617198
TI - Microbial regulation of GLP-1 and L-cell biology.
AB - BACKGROUND: The gut microbiota is associated with several of metabolic diseases,
including obesity and type 2 diabetes and affects host physiology through
distinct mechanisms. The microbiota produces a vast array of metabolites that
signal to host cells in the intestine as well as in more distal organs. SCOPE OF
REVIEW: Enteroendocrine cells acts as 'chemo sensors' of the intestinal milieu by
expressing a large number of receptors, which respond to different metabolites
and nutrients, and signal to host by a wide variety of hormones. However,
enteroendocrine cells differ along the length of the gut in terms of hormones
expressed and receptor repertoire. Also, the microbial ecology and dietary
substrates differ along the length of the gut, providing further evidence for
unique functions of specific subpopulations among enteroendocrine cells. Here we
will review how the gut microbiota interacts with L-cells in the small and large
intestine and the resulting effects on the host. MAJOR CONCLUSIONS: Microbial
metabolites can be sensed differently by specific subpopulations of
enteroendocrine cells. Furthermore, hormones such as GLP-1 can have different
functions when originating from the small intestine or colon. This article is
part of a special issue on microbiota.
PMID- 27617197
TI - How gut microbes talk to organs: The role of endocrine and nervous routes.
AB - BACKGROUND: Changes in gut microbiota composition and activity have been
associated with different metabolic disorders, including obesity, diabetes, and
cardiometabolic disorders. Recent evidence suggests that different organs are
directly under the influence of bacterial metabolites that may directly or
indirectly regulate physiological and pathological processes. SCOPE OF REVIEW: We
reviewed seminal as well as recent papers showing that gut microbes influence
energy, glucose and lipid homeostasis by controlling different metabolic routes
such as endocrine, enteric and central nervous system. These dialogues are
discussed in the context of obesity and diabetes but also for brain pathologies
and neurodegenerative disorders. MAJOR CONCLUSIONS: The recent advances in gut
microbiota investigation as well as the discovery of specific metabolites
interacting with host cells has led to the identification of novel inter-organ
communication during metabolic disturbances. This suggests that gut microbes may
be viewed as "novel" future therapeutic partners. This article is part of a
special issue on microbiota.
PMID- 27617203
TI - On the benefits of systematic reviews for wildlife parasitology.
AB - Systematic reviews and meta-analyses are widely accepted as the best means to
synthesise quantitative or qualitative scientific evidence. Many scientific
fields have embraced these more rigorous review techniques as a means to bring
together large and complex bodies of literature and their data. Unfortunately,
due to perceived difficulties and unfamiliarity with processes, other fields are
not using these options to review their literature. One way to provide guidance
for a specific field is to examine critically recent reviews and meta-analyses
and to explain the advantages and disadvantages of the various review techniques.
In this paper, we examine review papers in the emerging field of wildlife
parasitology and compare five different literature review types-configurative
narrative review, aggregative scoping review, aggregative literature review,
aggregative meta-analysis, and aggregative systematic review. We found that most
literature reviews did not adequately explain the methodology used to find the
literature under review. We also found that most literature reviews were not
comprehensive nor did they critically appraise the literature under review. Such
a lack severely reduces the reliability of the reviews. We encourage all authors
to consider using systematic reviews in the future, and for authors and peer
reviewers to be aware of the limitations of non-systematic reviews.
PMID- 27617202
TI - Interactions between host genetics and gut microbiome in diabetes and metabolic
syndrome.
AB - BACKGROUND: Diabetes, obesity, and the metabolic syndrome are multifactorial
diseases dependent on a complex interaction of host genetics, diet, and other
environmental factors. Increasing evidence places gut microbiota as important
modulators of the crosstalk between diet and development of obesity and metabolic
dysfunction. In addition, host genetics can have important impact on the
composition and function of gut microbiota. Indeed, depending on the genetic
background of the host, diet and other environmental factors may produce
different changes in gut microbiota, have different impacts on host metabolism,
and create different interactions between the microbiome and the host. SCOPE OF
REVIEW: In this review, we highlight how appropriate animal models can help
dissect the complex interaction of host genetics with the gut microbiome and how
diet can lead to different degrees of weight gain, levels of insulin resistance,
and metabolic outcomes, such as diabetes, in different individuals. We also
discuss the challenges of identifying specific disease-associated microbiota and
the limitations of simple metrics, such as phylogenetic diversity or the ratio of
Firmicutes to Bacteroidetes. MAJOR CONCLUSIONS: Understanding these complex
interactions will help in the development of novel treatments for microbiome
related metabolic diseases. This article is part of a special issue on
microbiota.
PMID- 27617201
TI - Non-alcoholic fatty liver and the gut microbiota.
AB - BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and
poorly understood liver disease whose incidence is globally rising. NAFLD is
generally asymptomatic and associated with other manifestations of the metabolic
syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory
liver disease termed non-alcoholic steatohepatitis (NASH) that may progress
towards cirrhosis, hepatocellular carcinoma, and the need for liver
transplantation. In recent years, several lines of evidence suggest that the gut
microbiome represents a significant environmental factor contributing to NAFLD
development and its progression into NASH. Suggested microbiome-associated
mechanisms contributing to NAFLD and NASH include dysbiosis-induced deregulation
of the gut endothelial barrier function, which facilitates systemic bacterial
translocation, and intestinal and hepatic inflammation. Furthermore, increased
microbiome-modulated metabolites such as lipopolysaccharides, short chain fatty
acids (SCFAs), bile acids, and ethanol, may affect liver pathology through
multiple direct and indirect mechanisms. SCOPE OF REVIEW: Herein, we discuss the
associations, mechanisms, and clinical implications of the microbiome's
contribution to NAFLD and NASH. Understanding these contributions to the
development of fatty liver pathogenesis and its clinical course may serve as a
basis for development of therapeutic microbiome-targeting approaches for
treatment and prevention of NAFLD and NASH. MAJOR CONCLUSIONS: Intestinal host
microbiome interactions play diverse roles in the pathogenesis and progression of
NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on
the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and
therapeutic targets of these common metabolic liver diseases. This article is
part of a special issue on microbiota.
PMID- 27617204
TI - First description of Onchocerca jakutensis (Nematoda: Filarioidea) in red deer
(Cervus elaphus) in Switzerland.
AB - Twenty-seven species of the genus Onchocerca (Nematoda; Filarioidea) can cause a
vector-borne parasitic disease called onchocercosis. Most Onchocerca species
infect wild and domestic ungulates or the dog, and one species causes river
blindness in humans mainly in tropical Africa. The European red deer (Cervus e.
elaphus) is host to four species, which are transmitted by blackflies (simuliids)
or biting midges (ceratopogonids). Two species, Onchocerca flexuosa and
Onchocerca jakutensis, produce subcutaneous nodules, whereas Onchocerca skrjabini
and Onchocerca garmsi live free in the hypodermal serous membranes. During the
hunting season, September 2013, red deer (n = 25), roe deer (Capreolus c.
capreolus, n = 6) and chamois (Rupicapra r. rupicapra, n = 7), all shot in the
Grisons Region (Switzerland) were investigated for the presence of subcutaneous
nodules which were enzymatically digested, and the contained Onchocerca worms
were identified to species by light and scanning electron microscopy as well as
by PCR/sequencing. In addition, microfilariae from skin samples were collected
and genetically characterized. Neither nodules nor microfilariae were discovered
in the roe deer and chamois. Adult worms were found in 24% of red deer, and all
of them were identified as O. jakutensis. Two morphologically different
microfilariae were obtained from five red deer, and genetic analysis of a skin
sample of one red deer indicated the presence of another Onchocerca species. This
is the first report of O. jakutensis in Switzerland with a prevalence in red deer
similar to that in neighbouring Germany.
PMID- 27617200
TI - Gut microbiota and immune crosstalk in metabolic disease.
AB - BACKGROUND: Gut microbiota is considered as a major regulator of metabolic
disease. This reconciles the notion of metabolic inflammation and the epidemic
development of the disease. In addition to evidence showing that a specific gut
microbiota characterizes patients with obesity, type 2 diabetes, and hepatic
steatosis, the mechanisms causal to the disease could be related to the
translocation of microbiota from the gut to the tissues, inducing inflammation.
The mechanisms regulating such a process are based on the crosstalk between the
gut microbiota and the host immune system. The hologenome theory of evolution
supports this concept and implies that therapeutic strategies aiming to control
glycemia should take into account both the gut microbiota and the host immune
system. SCOPE OF REVIEW: This review discusses the latest evidence regarding the
bidirectional impact of the gut microbiota on host immune system crosstalk for
the control of metabolic disease, hyperglycemia, and obesity. To avoid
redundancies with the literature, we will focus our attention on the intestinal
immune system, identifying evidence for the generation of novel therapeutic
strategies, which could be based on the control of the translocation of gut
bacteria to tissues. Such novel strategies should hamper the role played by gut
microbiota dysbiosis on the development of metabolic inflammation. MAJOR
CONCLUSIONS: Recent evidence in rodents allows us to conclude that an impaired
intestinal immune system characterizes and could be causal in the development of
metabolic disease. The fine understanding of the molecular mechanisms should
allow for the development of a first line of treatment for metabolic disease and
its co-morbidities. This article is part of a special issue on microbiota.
PMID- 27617199
TI - Causality of small and large intestinal microbiota in weight regulation and
insulin resistance.
AB - OBJECTIVE: The twin pandemics of obesity and Type 2 diabetes (T2D) are a global
challenge for health care systems. Changes in the environment, behavior, diet,
and lifestyle during the last decades are considered the major causes. A Western
diet, which is rich in saturated fat and simple sugars, may lead to changes in
gut microbial composition and physiology, which have recently been linked to the
development of metabolic diseases. METHODS: We will discuss evidence that
demonstrates the influence of the small and large intestinal microbiota on weight
regulation and the development of insulin resistance, based on literature search.
RESULTS: Altered large intestinal microbial composition may promote obesity by
increasing energy harvest through specialized gut microbes. In both large and
small intestine, microbial alterations may increase gut permeability that
facilitates the translocation of whole bacteria or endotoxic bacterial components
into metabolic active tissues. Moreover, changed microbial communities may affect
the production of satiety-inducing signals. Finally, bacterial metabolic
products, such as short chain fatty acids (SCFAs) and their relative ratios, may
be causal in disturbed immune and metabolic signaling, notably in the small
intestine where the surface is large. The function of these organs (adipose
tissue, brain, liver, muscle, pancreas) may be disturbed by the induction of low
grade inflammation, contributing to insulin resistance. CONCLUSIONS:
Interventions aimed to restoring gut microbial homeostasis, such as ingestion of
specific fibers or therapeutic microbes, are promising strategies to reduce
insulin resistance and the related metabolic abnormalities in obesity, metabolic
syndrome, and type 2 diabetes. This article is part of a special issue on
microbiota.
PMID- 27617205
TI - Molecular characterization of trypanosomatid infections in wild howler monkeys
(Alouatta caraya) in northeastern Argentina.
AB - The transmission of Trypanosoma cruzi by vectors is confined to the Americas, and
the infection circulates in at least two broadly defined transmission cycles
occurring in domestic and sylvatic habitats. This study sought to detect and
characterize infection by T. cruzi and other trypanosomes using PCR strategies in
blood samples from free-ranging howler monkeys, Alouatta caraya, in the
northeastern Argentina. Blood samples were collected at four sites with variable
levels of habitat modification by human activity. PCR was conducted using primers
for kinetoplast DNA, satellite DNA and ribosomal DNA of the trypanosomatid
parasites. Ribosomal and satellite DNA fragments were sequenced to identify the
trypanosomatid species and to characterize the discrete typing units (DTUs) of T.
cruzi. Overall, 46% (50/109) of the howlers were positive according to the kDNA
PCR assay, but only 7 of the howlers were positive according to the SatDNA-PCR
protocol. We sequenced the amplicons of the satellite DNA obtained from five
specimens, and the sequences were 99% and 100% similar to T. cruzi. A sequence
typical of DTU T. cruzi I was found in one howler monkey from the "remote" site,
while sequences compatible with DTUs II, V, and VI were found in howlers from the
"remote", "rural" and "village" sites. We detected 96% positive samples for
RibDNA-PCR, 9 of which were sequenced and displayed 99% identity with Trypanosoma
minasense, while none showed identity with T. cruzi. The results demonstrated the
presence of T. cruzi and a species closely related to T. minasense in blood
samples from free-ranging A. caraya, belonging to different T. cruzi DTUs
circulating in these howler monkey populations. The results obtained in this
study could help evaluate the role of A. caraya as a reservoir of T. cruzi in
regions where Chagas disease is hyper-endemic and where the human-wildlife
interface is increasing.
PMID- 27617208
TI - Rapidly developing and fatal Vibrio vulnificus wound infection.
PMID- 27617207
TI - Disseminated Nocardia farcinica in an immunocompetent patient.
AB - Nocardia farcinica is a gram-positive, partially acid-fast, methenamine silver
positive aerobic actinomycete that is infrequently associated with nocardiosis.
The relative frequency of Nocardia farcinica isolates in nocardiosis is unknown
but thought to be under diagnosis. It is increasingly been recognized in
immunocompetent patients. We report a case of disseminated Nocardia farcinica
causing brain abscess in 55 year old immunocompetent man who was successfully
treated with long term antibiotics. The present report illustrates that early
detection and treatment of disseminated Nocardia farcinica can lead to a good
outcome.
PMID- 27617206
TI - The genome of the insecticidal Chromobacterium subtsugae PRAA4-1 and its
comparison with that of Chromobacterium violaceum ATCC 12472.
AB - The genome of Chromobacterium subtsugae strain PRAA4-1, a betaproteobacterium
producing insecticidal compounds, was sequenced and compared with the genome of
C. violaceum ATCC 12472. The genome of C. subtsugae displayed a reduction in
genes devoted to capsular and extracellular polysaccharide, possessed no genes
encoding nitrate reductases, and exhibited many more phage-related sequences than
were observed for C. violaceum. The genomes of both species possess a number of
gene clusters predicted to encode biosynthetic complexes for secondary
metabolites; these clusters suggest they produce overlapping, but distinct
assortments of metabolites.
PMID- 27617209
TI - Coxsackie B5 infection in an adult with fever, truncal rash, diarrhea and
splenomegaly with highly elevated ferritin levels.
AB - Coxsackie viruses are enteroviruses most common in children. Coxsackie B viral
infections often present with biphasic fever, headache, pharyngitis,
nausea/vomiting, diarrhea and a maculopapular rash that spares the palms and
soles. These clinical features may be present in other viral infections. We
present a case of a hospitalized adult with rash and fever with highly elevated
ferritin levels later found to be due to Coxsackie B5. We believe this is the
first case of Coxsackie B infection with otherwise unexplained highly elevated
ferritin levels.
PMID- 27617210
TI - Heterophile Antibody Interference led to Unneeded Chemotherapy in a Testicular
Cancer Patient.
AB - Human heterophile antibodies may develop after infection or contact with animal
tissues or animal serum products. These antibodies have the capacity to bind to
the animal immunoglobulins used in immunoassays leading to erroneous results. We
here report a case of a testicular germ cell tumor patient who developed
heterophile antibodies during the surveillance period of his disease. Following
false-positive results of human chorionic gonadotropin (hCG) he received unneeded
chemotherapy. This article also stresses the problem of using serum tumor markers
without no major imaging abnormalities to diagnose a patients' relapse.
PMID- 27617211
TI - "Isolated Spontaneous Renal Artery Thrombosis - A Rare Cause of Acute Flank
Pain".
AB - Many patients present with severe abdominal pain. Renal Artery Thrombosis (RAT)
is rare, serious and misdiagnosed. RAT has been well described in association
with various disorders, but isolated spontaneously occurring RAT is rare and only
2 cases have been described as of date. We present a case of flank pain
presenting to emergency for evaluation and discuss the clinical aspects and
management. We would like to stress on the important role of serum LDH levels and
CT scan in RAT. Early diagnosis may result in salvage of organ by minimally
invasive techniques. Late diagnosis will almost always result in nephrectomy.
PMID- 27617212
TI - Spontaneous Ureteral Urine Extravasation From Invasion of a High-grade
Angiosarcoma.
AB - A 69 year-old male with a past medical history of hypertension, diabetes, and
atrial fibrillation presented to the Urology clinic with asymptomatic microscopic
hematuria. His work up for hematuria included a negative cystoscopy and a
computed tomography (CT) scan, which revealed what appeared to be a fluid
collection around the left kidney with a perinephric infiltrative mass and two
para-aortic enlarged lymph nodes.
PMID- 27617213
TI - Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at
Inception in a Patient Under Close Surveillance for Lung Cancer.
AB - Adrenocortical carcinoma (ACC) is a rare malignancy that is generally associated
with a poor prognosis whose existence dictates the management of incidental renal
masses. We report a case of ACC diagnosed and treated at its apparent inception
in a patient undergoing close surveillance imaging of a prior malignancy. Despite
timely detection and resection of a localized ACC this patient rapidly progressed
to systemic disease. This case highlights the rapid growth kinetics of ACC and
puts into perspective the challenges associated with the established treatment
paradigm for patients diagnosed with an adrenal mass.
PMID- 27617214
TI - Rare Dysuria: Prostatic Abscess due to Disseminated Coccidioidomycosis.
AB - We present a case of disseminated coccidioidomycosis with formation of a
prostatic abscess in a 28-year-old diabetic male. Though rare, Coccidiodes
prostatitis should be included in the differential for patients who have spent
time in endemic areas and present with prostatitis or other genitourinary tract
symptoms, especially in the setting of immunocompromise. The small number of
Coccidiodes prostatitis cases described in the literature previously are
reviewed, along with a wider discussion of coccidioidomycosis. Treatment
modalities for this challenging fungal disease are also discussed.
PMID- 27617215
TI - Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair.
AB - Methylene blue is an intravenously administered agent that may potentiate
serotonin syndrome. The usage of methylene blue to evaluate ureters for injuries
and patency during urological surgeries is recognized as common practice.
However, there is no mention of serotonin syndrome caused by methylene blue in
urological literature or for urological surgery. We report the first urological
case in order to raise awareness of the risk for serotonin toxicity with
utilizing methylene blue.
PMID- 27617216
TI - Association of TFAP2A gene polymorphism with susceptibility to non-syndromic
cleft lip with or without palate risk in south Indian population.
AB - The aetiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) is
complex involving multiple interacting genes and environmental factors. The
primary objective of the present study was to investigate the role of TFAP2A gene
single nucleotide polymorphisms (SNPs) in the pathogenesis of NSCL/P. In this
study, 173 unrelated NSCL/P patients and 176 controls without clefts were
genotyped with TFAP2A rs1675414 (Exon 1), rs3798691 (Intron 1), and rs303050
(Intron 4) variants by allele-specific amplification using the KASPar SNP
genotyping system. The method of multifactor dimensionality reduction (MDR) was
used to analyze gene-gene interactions. TFAP2A polymorphisms are not found to be
associated with non-syndromic cleft lip with or without cleft palate (NSCL/P) at
either the genotype or allele levels. No linkage disequilibrium (LD) was found
between TFAP2A variants. MDR analysis did not show a significant effect of the
TFAP2A gene polymorphisms on susceptibility to NSCL/P (p > 0.05). These results
suggest that the analyzed variations in TFAP2A gene might not be associated with
NSCL/P pathogenesis in south Indian population.
PMID- 27617217
TI - Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal
gynecomastia: Clinical, chromosomal and aCGH characterization.
AB - We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2
q21.31 duplication delimited by aCGH. As previously described in patients with
similar duplications, his clinical features included intellectual disability,
developmental delay, speech delay, generalized hypotonia, infantile feeding
difficulties, self-injurious behavior, short stature and endocrine problems. As
additional findings, he presented recurrent seizures and pubertal gynecomastia.
His mother was phenotypically normal and had completely skewed inactivation of
the duplicated X chromosome, as most female carriers of such duplications. Five
previously reported patients with partial Xq duplications presented duplication
breakpoints similar to those of our patient. One of them, a fetus with multiple
congenital abnormalities, had the same cytogenetic duplication breakpoint. Three
of the reported patients shared many features with our proband but the other had
some clinical features of the Prader-Willi syndrome. It was suggested that ATRX
overexpression could be involved in the major clinical features of patients with
partial Xq duplications. We propose that this gene could also be involved with
the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we
suggest that the PCDH11X gene could be a candidate for our patient's recurrent
seizures. In males, the Xq13-q21 duplication should be considered in the
differential diagnosis of Prader-Willi syndrome, as previously suggested, and
neuromuscular diseases, particularly mitochondriopathies.
PMID- 27617218
TI - Identification of TRPCs genetic variants that modify risk for lung cancer based
on the pathway and two-stage study.
AB - OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium
channels (ROCCs) are important pathways participating in regulation of
intracellular Ca(2 +) concentration in various cell types. The purpose of our
study is to determine whether genetic variations in key components of SOCCs and
ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in
9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1,
ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in
a two-stage case-control study with a total of 2433 lung cancer cases and 2433
cancer-free controls using Illumina high throughput genotyping platform. RESULTS:
We found consistently significant associations of TRPC4 rs9547991 and rs978156,
and TRPC7 rs11748198 with increased risk of lung cancer among the three kinds of
sources of populations (additive model in combined population: adjusted OR =
1.33, 95% CI = 1.11-1.59 for rs9547991; adjusted OR = 1.21, 95% CI = 1.08-1.35
for rs978156; and adjusted OR = 1.28, 95% CI = 1.10-1.47 for rs11748198). When
combining the effects of TRPC7 rs11748198, and TRPC4 rs9547991 and rs978156,
subjects carrying ">= 1" variant alleles had a 1.29-fold increased risk of lung
cancer (95% CI = 1.15-1.46), compared with those carrying "0" variant allele.
Lung cancer risk significantly increased with the increasing number of variant
alleles of the three SNPs in a dose-dependent manner (P for trend = 7.2 * 10(-
7)). CONCLUSION: These findings suggested that TRPC4 rs9547991 and rs978156, and
TRPC7 rs11748198 were candidate susceptibility markers for lung cancer in Chinese
population. Our study provides the epidemiological evidence supporting a
connection between TRPC members and lung cancer risks.
PMID- 27617220
TI - Association of adiponectin receptor 1 gene - 106 C > T variant with
susceptibility to colorectal cancer.
AB - BACKGROUND: Colorectal cancer (CRC) is the fourth leading cause of cancer-related
death around the world and accumulated evidence indicates the association between
CRC and obesity and insulin resistance. OBJECTIVES: Regarding the role of
adiponectin in obesity and insulin resistance, we explored whether genetic
variants in adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) are
associated with CRC risk. MATERIALS AND METHODS: ADIPOQ (rs2241766) and ADIPOR1
(rs2275738) gene variants were genotyped in 261 cases with CRC and 339 controls
using PCR-RFLP method. RESULTS: In this study, no significant difference was
observed for ADIPOQ gene rs2241766 variant between the cases and controls.
However, carriers of the ADIPOR1 (rs2275738) "CC + CT" genotype compared with
"TT" genotype occurred more frequently in the cases with CRC than the controls,
and the difference remained significant after adjustment for age, BMI, sex,
smoking status, NSAID use, and family history of CRC (P = 0.048; OR = 1.49, 95%CI
= 1.01-2.20). Interestingly, after adjustment for confounding factors the ADIPOR1
"CC + TC" genotype compared with "TT" genotype was also associated with an
increased risk for obesity in the cases (P = 0.040; OR = 1.86, 95%CI = 1.03
3.36). CONCLUSIONS: Our findings suggest for the first time that the - 106 C > T
(rs2275738) variant of ADIPOR1 gene may be a genetic contributor to CRC and
obesity risk in the cases with CRC. However, further studies with bigger sample
size are needed to validate these findings.
PMID- 27617219
TI - Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin
dosage in Han-Chinese patients: A systematic review and meta-analysis.
AB - INTRODUCTION: Warfarin is the most commonly used antithrombotic drug. Single
nucleotide polymorphisms (SNPs) of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639
influence warfarin maintenance dosage. We aimed to determine the impact of SNPs
of these genes on mean daily warfarin dosage (MDWD) in Han-Chinese patients.
METHODS: Strict literature inclusion criteria were established, and literature
searching was performed on PubMed, Embase and Cochrane Library for English
articles and CNKI, CBM and Wanfang database for Chinese articles before September
2, 2014. Revman 5.3 was used to analyze the relationship between gene SNPs and
MDWD in Han-Chinese subjects. RESULTS: We included 33 studies researching the
impact of gene SNPs on MDWD in Han-Chinese subjects. CYP2C9 *3/*3, *1/*3 and *3
carriers needed a 72% (95% confidence interval [CI]: 62.0%-81.0%), 28% (22.0%
33.0%) and 26% (21.0%-32.0%) lower MDWD, respectively, than CYP2C9 *1/*1
carriers. CYP4F2 TT, CT and T carriers required a 18% (7.0%-30.0%), 7% (7.0%
7.0%) and 11% (7.0%-14.0%) higher MDWD, respectively, than CYP4F2 CC carriers.
VKORC1 1173 CC, CT and C carriers required a 98% (78.0%-118.0%), 49% (37.0%
62.0%) and 56% (44.0%-67.0%) higher MDWD, respectively, than VKORC1 1173 TT
carriers. VKORC1-1639 GG, GA and G carriers needed a 101% (53.0%-149.0%), 40%
(36.0%-45.0%) and 38% (35.0%-42.0%) higher MDWD, respectively, than VKORC1-1639
AA carriers. CONCLUSIONS: This meta-analysis is the first to report the
relationship between genotypes and MDWD among Han-Chinese patients. The results
showed that SNPs of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 significantly
influenced the MDWD in Han-Chinese patients.
PMID- 27617221
TI - Two gene polymorphisms (rs4977756 and rs11515) in CDKN2A/B and glioma risk in
South Indian population.
AB - Gliomas are most common neoplasms in the CNS with unknown aetiology. Gene
polymorphisms have been studied in glioma to check its risk in different
population. CDKN2A, commonly altered tumor suppressor gene polymorphisms were
recently shown to be associated with glioma in Caucasians. Present study
evaluated potential association between two SNPs in CDKN2A/B gene with glioma
risk in South Indian population with a total of 128 cases and 140 control
subjects. Allelic discrimination assay was used for the genotyping and the
association of each SNP with glioma risk were calculated using odds ratio and 95%
CI. There was no association between rs4977756 polymorphism and glioma risk in
south Indian population. GG genotype had a non-significant low risk in glioma (OR
= 0.69). rs11515 polymorphism was not in Hardy Weinberg Equilibrium in our
sample, so it was not considered for association studies. There was difference in
genotype in tissue samples paired with blood samples for rs4977756 polymorphism,
suggesting the importance of tissue SNP status in association studies. These
results show that these two polymorphisms may not contribute to risk for glioma
in South Indian population.
PMID- 27617222
TI - Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children
with Wolfram syndrome.
AB - Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder
characterized by the presentation of early onset type I diabetes mellitus and
optic atrophy with later onset diabetes insipidus and deafness. WFS1 gene was
identified on chromosome 4p16.1 as the gene responsible for WS disease given that
most of the WS patients were found to carry mutations in this gene. This study
was carried out to investigate the molecular spectrum of WFS1 gene in Jordanian
families. Molecular and clinical characterization was performed on five WS
patients from two unrelated Jordanian families. Our data indicated that WS
patients of the first family harbored two deletion mutations (V415del and F247fs)
located in exon 8 and exon 7 respectively, with a compound heterozygous pattern
of inheritance; while in the second family, we identified a novel nonsense
mutation (W185X) located in exon 5 in the N-terminal cytoplasmic domain with a
homozygous pattern of inheritance. This mutation can be considered as loss of
function mutation since the resulting truncated protein lost both the
transmembrane domain and the C-terminal domain. Additionally, the W185X mutation
lies within the CaM binding domain in wolframin protein which is thought to have
a role in the regulation of wolframin function in response to calcium levels.
PMID- 27617223
TI - An enhanced version of Cochran-Armitage trend test for genome-wide association
studies.
AB - Genome-wide association studies the evaluation of association between candidate
gene and disease status is widely carried out using Cochran-Armitage trend test.
However, only a small number of research papers have evaluated the distribution
of p-values for the Cochran-Armitage trend test. In this paper, an enhanced
version of Cochran-Armitage trend test based on bootstrap approach is introduced.
The achieved results confirm that the distribution of p-values of the proposed
approach fits better to the uniform distribution, and it is thus concluded that
the proposed method, which needs less assumptions in comparison with the
conventional method, can be successfully used to test the genetic association.
PMID- 27617224
TI - Sequence analysis of Meq oncogene among Indian isolates of Marek's disease
herpesvirus.
AB - Marek's disease (MD), caused by Marek's disease virus (MDV), is a highly
contagious neoplastic disease of chicken that can be prevented by vaccination.
However, in recent years many cases of vaccine failure have been reported
worldwide as chickens develop symptoms of MD in spite of proper vaccination.
Distinct polymorphism and point mutations in Meq gene of MDV have been reported
to be associated with virulence and oncogenicity. The present study was carried
out with the objective to isolate and characterize field isolates of MDV on the
basis of Meq gene. Twenty five samples of suspected cases of MD were collected
and processed for virus isolation in duck embryo fibroblast (DEF) primary culture
where 28% (7 of 25) samples showed characteristic cytopathic effects of MDV in
the form of plaques and syncytia. Additional evidence of presence of MDV in these
samples was confirmed by PCR. To analyze diversity in all seven isolates of MDV,
a polymorphism study was carried out by cloning and sequencing of full length of
Meq gene (1020 bp). Sequence homology of 7 isolates with 23 reference strains
showed 98.10-99.40% similarity in nucleotide and 95.90-98.50% similarity in amino
acid sequences. Six isolates revealed 5 repeat sequences of 4 prolines (PPPP)
whereas, one isolate revealed only 4 repeats. In phylogenetic analysis, these
isolates formed a separate cluster showing close relatedness to the Chinese
isolates. The study indicates a high mutation rate in field isolates of MDV that
may be probable cause of vaccination failure.
PMID- 27617226
TI - Vascular endothelial growth factor gene polymorphisms and association with age
related macular degeneration in Indian patients.
AB - BACKGROUND: Age-related macular degeneration (AMD) is an important cause of
visual impairment in elderly people. AMD is a multifactorial disease in which
both environmental and genetic factors have been implicated. Various single
nucleotide polymorphisms (SNPs) have been found to be associated with AMD. AIM:
This study was aimed to investigate the association of polymorphisms in VEGF
genes with age related macular degeneration (AMD) in Indian patients. METHOD:
Genotyping for the VEGF - 1154 (G > A), - 2578 (C > A), + 405 (G > C) and - 460
(C > T) SNPs was performed in 100 AMD patients and 100 controls by polymerase
chain reaction (PCR), restriction fragment length polymorphism (PCR-RFLP) and
sequencing method. RESULTS: Out of the four SNPs, heterozygous genotypes of VEGF
1154 G > A (OR = 2.58, p = 0.0035), + 460 C > T (OR = 2.90, p = 0.0046), and +
405 G > C (OR = 2.02, p = 0.02) have shown susceptible association with AMD.
However, VEGF - 2578 C > A did not show any statistical significance. Further A-A
G-T haplotype comprising of three mutant alleles revealed risk association (OR =
12.7, p = 0.0030) with AMD. CONCLUSION: The present study suggests significant
genetic associations for VEGF - 1154 G > A, + 460 C > T, and + 405 G > C
polymorphisms with AMD. Early detection of individuals with risk to these SNPs
could lead to strategies for prevention, early diagnosis, and management of AMD.
PMID- 27617225
TI - Investigating regulatory signatures of human autophagy related gene 5 (ATG5)
through functional in silico analysis.
AB - Autophagy is an essential, homeostatic process which removes damaged cellular
proteins and organelles for cellular renewal. ATG5, a part of E3 ubiquitin ligase
like complex (Atg12-Atg5/Atg16L1), is a key regulator involved in autophagosome
formation - a crucial phase of autophagy. In this study, we used different in
silico methods for comprehensive analysis of ATG5 to investigate its less
explored regulatory activity. We have predicted various physico-chemical
parameters and two possible transmembrane models that helped in exposing its
functional regions. Twenty four PTM sites and 44 TFBS were identified which could
be targeted to modulate the autophagy pathway. Furthermore, LD analysis
identified 3 blocks of genotyped SNPs and 2 deleterious nsSNPs that may have
damaging impact on protein function and thus could be employed for carrying
genome-wide association studies. In conclusion, the information obtained in this
study could be helpful for better understanding of regulatory roles of ATG5 and
provides a base for its implication in population-based studies.
PMID- 27617227
TI - Interleukin 10 (- 1082 G/A) and (- 819 C/T) gene polymorphisms in Egyptian women
with polycystic ovary syndrome (PCOS).
AB - Cytokines play critical roles in the pathogenesis of Polycystic Ovarian Syndrome
(PCOS). This work was designed to study the implication of IL10 gene
polymorphisms (- 1082 G/A and - 819 C/T) on the susceptibility of Egyptian women
to have PCOS. Rotterdam consensus criteria were used to diagnose PCOS patients.
Genotyping was performed by single-stranded polymorphism-polymerase chain
reaction (SSP-PCR) in 61 PCOS patients and 80 healthy controls, and IL-10 serum
levels were measured using Enzyme linked immunosorbent assay (ELISA). The
frequency of IL10 - 1082 G/G (46%) genotype was significantly increased (p <
0.001) while the frequency of - 1082 A/A (16%) genotype was significantly
decreased (p < 0.05) in PCOS patients compared to controls (14% and 35% for G/G
and A/A genotypes; respectively). G allele (65%) is significantly increased (p <
0.01( in PCOS patients while A allele (61%) is significantly increased (p <
0.001( in control subjects. The distribution of IL10 -819 T/T genotype was
significantly increased (p < 0.05) in PCOS group. G/G genotype (odd ratio (OR =
5.322) with confidence interval (CI = 2.364-11.982) and the G allele (OR = 2.828
with CI = 1.73-4.61) of - 1082 G/A and T/T genotype of - 819 C/T (OR = 4.18 with
CI = 1.26-13.86) could be considered as risk factors for PCOS. IL-10 levels were
significantly lower among PCOS patients (313.42 +/- 30.10) compared to normal
controls (4914.36 +/- 303.72). Depending on our preliminary work, IL10 - 1082 G/G
might be considered as a host genetic factor for PCOS susceptibility in Egyptian
women. Studies concerning other cytokine gene polymorphisms are required to get a
better understanding of the pathogenesis of PCOS disease.
PMID- 27617228
TI - Treatment with recombinant human bone morphogenetic protein 7 leads to a
transient induction of neutralizing autoantibodies in a subset of patients.
AB - BACKGROUND: Recombinant human bone morphogenetic protein 7 (rhBMP7) is applied
for treatment of bone fractures, especially tibial non-unions. Its application
may induce autoantibodies (aAB) affecting the targeted and endogenous signaling
pathways and in turn negatively impact treatment efficacy. METHODS: Novel and
sensitive assays for the quantification of BMP7-aAB and BMP2-aAB were established
and used to analyze serum samples from healthy controls (n = 100 men, n = 100
women) and patients with long bone fracture (n = 265) treated or not with rhBMP7.
Sera from three to nine time points per patient were available and enabled the
evaluation of aAB over a time course of up to one year. Functional activity of
the BMP-aAB was tested with a BMP-responsive cell-based reporter assay.
Consolidation of the fracture was evaluated as clinical outcome potentially
affected by BMP7-aAB. RESULTS: Prevalence of BMP7-aAB and BMP2-aAB was 1-2.5% in
non-treated patients or healthy controls. The rhBMP7 treatment induced a
transient increase in BMP7-aAB in a subset of patients, returning to non
detectable levels within six months. IgG from BMP7-aAB positive sera inhibited
dose dependently the BMP7-reporter gene activity, whereas control sera were
without effect. Successful consolidation of the fracture was observed in the
majority of both aAB-positive and aAB-negative patients. GENERAL SIGNIFICANCE: We
conclude that BMP7-aAB can be detected as natural aAB in healthy subjects, and
are transiently induced by rhBMP7 therapy in a subset of patients. The aAB are
capable of antagonizing BMP7 signaling in vitro, but do not preclude treatment
success in patients.
PMID- 27617229
TI - Influence of primer & probe chemistry and amplification target on reverse
transcription digital PCR quantification of viral RNA.
AB - Compared to other PCR technologies, digital PCR is a potentially highly accurate
approach for the quantification of nucleic acid fragments. This study describes
the impact of four experimental factors, namely primer and probe chemistry, PCR
amplification target, duplexing, and template type, on the measurement results
obtained by reverse transcription digital PCR (RT-dPCR) of viral RNA using
influenza A virus as a model. Along conventional dual labelled probes (DLP),
alternative primer and probe chemistries, including Zip Nucleic Acids (ZNAs),
Locked Nucleic Acids (LNAs), and Scorpions((r)), were compared with two RNA
template types: i) total genomic RNA extracted from cell cultured influenza A and
ii) a synthetically prepared RNA transcript (In vitro transcribed RNA). While
apparently duplexing or a different PCR target choice did not have a significant
influence on the estimated RNA copy numbers, the impact of the choice of primer
and probe chemistry and template type differed significantly for some methods.
The combined standard uncertainty of the dPCR analysis results has been assessed,
taking into account both the repeatability and the intermediate precision of the
procedure. Our data highlight the importance of dPCR method optimisation and the
advantage of using a more sophisticated primer and probe chemistry, which turned
out to be dependent on the template type. Considerations are provided with
respect to the molecular diagnostics of viral RNA pathogens, and more
specifically, for precise quantification of RNA, which is of tremendous
importance for the development of RNA calibration materials and the qualification
of these calibrants as certified reference materials.
PMID- 27617230
TI - Validation of a digital PCR method for quantification of DNA copy number
concentrations by using a certified reference material.
AB - Digital PCR has become the emerging technique for the sequence-specific detection
and quantification of nucleic acids for various applications. During the past
years, numerous reports on the development of new digital PCR methods have been
published. Maturation of these developments into reliable analytical methods
suitable for diagnostic or other routine testing purposes requires their
validation for the intended use. Here, the results of an in-house validation of a
droplet digital PCR method are presented. This method is intended for the
quantification of the absolute copy number concentration of a purified linearized
plasmid in solution with a nucleic acid background. It has been investigated
which factors within the measurement process have a significant effect on the
measurement results, and the contribution to the overall measurement uncertainty
has been estimated. A comprehensive overview is provided on all the aspects that
should be investigated when performing an in-house method validation of a digital
PCR method.
PMID- 27617231
TI - Use of cross-reactivity immunoassay to orient insulin replacement in diabetic
patients with high levels of insulin antibodies.
AB - The prevalence and high levels of anti-insulin antibodies (IA) have frequently
been associated with brittle diabetes, lipodystrophy in the areas where the
insulin is injected and/or poor metabolic control. When this happens the usual
criterion adopted is the empirical change of insulin type and/or formulation
intending to diminish the IA level and then to decrease the undesirable side
effects. Here, we present a rational two step radiometric method consisting in:
A) a first-line radioligand binding assay (RBA) to assess IA in sera of these
patients and detecting those with high levels. B) applying a displacement assay
(RIA) to determine the in vitro cross-reactivity parameters (affinity constants
and selectivity ratios) that quantify the relative degree of interaction between
antibodies and alternative insulin analogs. From these results we conclude that
conventional criteria for selection of insulin analogs, in terms of
pharmacokinetic and pharmacodinamic parameters, should be complemented with an
appropriate test to assess affinity parameters when high IA title is
demonstrated. *This manuscript introduces a rational method to determine the
appropriated insulin replacement when high insulin antibodies levels are
present.*This protocol provides instructions and details in mathematical tools
and laboratory processes for the analysis of serum samples.*This method proved to
be successful in a single case and requires confirmation using a large group of
patients.
PMID- 27617232
TI - Protective Effect of Carnobacterium spp. against Listeria monocytogenes during
Host Cell Invasion Using In vitro HT29 Model.
AB - The pathogenesis of listeriosis results mainly from the ability of Listeria
monocytogenes to attach, invade, replicate and survive within various cell types
in mammalian tissues. In this work, the effect of two bacteriocin-producing
Carnobacterium (C. divergens V41 and C. maltaromaticum V1) and three non
bacteriocinogenic strains: (C. divergens V41C9, C. divergens 2763, and C.
maltaromaticum 2762) was investigated on the reduction of L. monocytogenes Scott
A plaque-forming during human infection using the HT-29 in vitro model. All
Carnobacteria tested resulted in a reduction in the epithelial cell invasion
caused by L. monocytogenes Scott A. To understand better the mechanism underlying
the level of L. monocytogenes infection inhibition by Carnobacteria, infection
assays from various pretreatments of Carnobacteria were assessed. The results
revealed the influence of bacteriocin production combined with a passive
mechanism of mammalian cell monolayers protection by Carnobacteria. These initial
results showing a reduction in L. monocytogenes virulence on epithelial cells by
Carnobacteria would be worthwhile analyzing further as a promising probiotic tool
for human health.
PMID- 27617234
TI - Migraine and type 2 diabetes; is there any association?
AB - BACKGROUND: Migraine headache prevalence and triggers in type2 diabetes mellitus
(T2DM) were investigated in previous studies but the results are contradictory.
Therefore, in this study we examined the prevalence of migraine headache in
diabetic patients in comparison with non-diabetic persons and its predisposing
factors in 2014. METHODS: We enrolled 147 volunteer patients with T2DM and 150
healthy persons referred to the Yazd Diabetes Research Center and the Central
Laboratory of Yazd, respectively, in 2014. The data collection instrument was a
self-conducted checklist. The checklist contained demographic, anthropometric and
clinical characteristics and migraine diagnostic questions according to
International Classification of Headache Disorders Second Edition (ICHD-II)
criteria. We compared prevalence of migraine between two groups, and also
evaluated relationship between above characteristics and migraine prevalence in
both groups. RESULTS: The prevalence of migraine in participants of diabetic and
non-diabetic was 27.9 and 26 %, respectively (p-value = .406). The prevalence of
migraine headache among in diabetic persons was significantly correlated with
family history of migraine, diabetes duration and hypoglycemia attacks. Also, the
migraine prevalence was significant more prevalent in T2DM patients with duration
6-10 years (p-value = 0.031). The percentage of HbA1C, type of anti-diabetic
medication, BMI value and age in diabetic patients did not show any significant
association with migraine. CONCLUSION: Although we observed no significant
differences in prevalence of migraine between patients with T2DM and non-diabetic
age and sex adjusted persons But, the occurrence of hypoglycemia attacks and T2DM
duration were related to migraine prevalence. Decreasing hypoglycemia among long
time T2DM patients probably can decline migraine headache in this group of
patients.
PMID- 27617235
TI - A Study of The Effects of Novel Rhenium Compounds on Pancreatic and Prostate
Cancer Cell Lines.
PMID- 27617233
TI - Modulation of the Inflammasome Signaling Pathway by Enteropathogenic and
Enterohemorrhagic Escherichia coli.
AB - Innate immunity is an essential component in the protection of a host against
pathogens. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and
EHEC, respectively) are known to modulate the innate immune responses of infected
cells. The interference is dependent on their type III secretion system (T3SS)
and T3SS-dependent effector proteins. Furthermore, these cytosolically injected
effectors have been demonstrated to engage multiple immune signaling pathways,
including the IFN/STAT, MAPK, NF-kappaB, and inflammasome pathways. In this
review, recent work describing the interaction between EPEC/EHEC and the
inflammasome pathway will be discussed.
PMID- 27617236
TI - Management of Menopausal Symptoms in Mongolia.
PMID- 27617237
TI - HIFU: Effects and Clinical Effectiveness of Non-surgical Therapy for Uterine
Fibroids.
PMID- 27617238
TI - Hops for Menopausal Vasomotor Symptoms: Mechanisms of Action.
AB - Menopause is a critical stage of women's life associated with various complaints
and distresses. Vasomotor symptoms (VMS), such as hot flushes, night sweats,
sleep disturbances, and fatigue, are the most common menopause symptoms affecting
about 50% to 80% of middle-aged women. Obviously, these symptoms, resulting from
estrogen deficiency during menopause, can exert negative effects on women's
health and quality of life and thus require to be managed through approaches such
as hormone replacement therapy (HRT). Many herbal treatments for menopause
symptoms contain and its components such as 8-prenylnaringenin, 6-PN,
isoxanthohumol and xanthohumol. Recent in-vivo studies have highlighted the
ability of 8-prenylnaringenin to reduce serum-luteinizing hormone (LH) and
follicle-stimulating hormone (FSH), to increase serum prolactin levels and
uterine weight, and to induce vaginal hyperplastic epithelium. Previous research
has shown that hops extract can strongly bind to both estrogen receptors,
stimulate alkaline phosphatase activity in Ishikawa cells, and upregulate
presenelin-2 and progesterone receptor mRNA in Ishikawa cells. Numerous clinical
trials have documented significant reductions in the frequency of hot flushes
following the administration of hop-containing preparations. Nevertheless,
further clinical trials with larger sample size and longer follow-up are
warranted to confirm such benefits.
PMID- 27617239
TI - Cervical Cancer Screening after Perimenopause: How Is Human Papillomavirus Test
Performed?
AB - Cervical cancer is the third most prevalent cancer in women around the world.
Recently in Korea, the incidence of cervical cancer has decreased, but in all
stages of cervical intraepithelial neoplasia (CIN), CIN has shown a 91% increase
from 1999 to 2008. Persistent human papillomavirus (HPV) infection has been found
to be the main cause of cervical cancer. HPV types 16 and 18 have been found in
70% of cervical cancer patients around the world. Cervical cancer screening such
as cytology has limitations in terms of sensitivity and specificity. A discussion
about the need for the HPV test is becoming active in order to compensate for the
limitation of cytology. After the role of HPV in cervical cancer was identified,
the importance of HPV detection test as a screening was emphasized. Several tests
have been developed and each test has its own advantages and disadvantages, and
new test method to overcome the disadvantages is still being developed. Today's
guidelines and tests are those you would choose from among the large number of
cervical cancer screening guidelines and tests, based on the consideration that
the selected guidelines and the test are effective.
PMID- 27617240
TI - Cell Therapy Products in Menopausal Medicine.
AB - The incidence of postmenopausal diseases increases with the age of women. In this
review, we introduce cell therapy products, a new treatment for postmenopausal
osteoporosis, which often occurs in postmenopausal women. We also figure out the
trends of research on cell therapy products and emphasize the necessity and
importance of this research for researchers and postmenopausal women. Finally, we
suggest the direction for improvement of postmenopausal osteoporosis and research
on cell therapy products. We investigated which medication have been used so far.
We also examined the development and technical problems of technologies that are
currently in use.
PMID- 27617241
TI - Postmenopausal Osteoporosis Is Associated with Serum Chemerin and Irisin but Not
with Apolipoprotein M Levels.
AB - OBJECTIVES: The objective of this study was to describe the levels of chemerin,
irisin and apolipoprotein M (apoM) in women with postmenopausal osteoporosis.
METHODS: The study included 88 women with postmenopausal osteoporosis. Based on
World Health Organization criteria, women with a T-score of <= -2.5 were defined
as osteoporotic. In this case-control study, postmenopausal women with T-score >
1 were selected as controls (n = 88) and case-matched in a 1:1 ratio based on age
(within 2 years) and body mass index (BMI) (within 1.0 kg/m(2)). ApoM, irisin and
chemerin levels were determined by a commercially available enzyme-linked
immunosorbent assay (ELISA) kit. RESULTS: There were no significant differences
in age, BMI, parity, cholesterol and apoM levels between the two groups. C
reactive protein levels were significantly increased in women with osteoporosis.
Serum chemerin levels (240.1 +/- 46.1 vs. 261.5 +/- 50.8 ng/mL) were
significantly lower in the women with osteoporosis, as compared to the controls
(P = 0.004). Serum irisin levels were also decreased in women with osteoporosis
(0.7 +/- 0.2 vs. 0.8 +/- 0.2 ng/mL; P = 0.007). CONCLUSION: In the present study,
osteoporosis was associated with decreased levels of circulating chemerin and
irisin. These findings suggested that adipokines might play a role in the
pathogenesis of osteoporosis.
PMID- 27617242
TI - Correlation between Female Sex Hormones and Electrodiagnostic Parameters and
Clinical Function in Post-menopausal Women with Idiopathic Carpal Tunnel
Syndrome.
AB - OBJECTIVES: To investigate the role of sex-hormonal changes in idiopathic carpal
tunnel syndrome (CTS) among post-menopausal women through measuring estrogen
receptor (ER) expression in their transverse carpal ligament (TCL) and serum
estrogen level, as well as determine the correlation between these factors and
electrodiagnostic parameters and Boston score. METHODS: Biopsy samples of TCL
were collected from 12 postmenopausal women who had undergone surgery for severe
idiopathic CTS; control specimens were collected from 10 postmenopausal women
without CTS who had undergone surgery for the other hand pathologies. To
determine the distributions of ER in TCL, histological and immunohistochemical
examinations were performed. Serum estrogen level was also measured.
Electrodiagnosis and Boston questionnaire were used for CTS severity and
determination of the patients' function. RESULTS: ER expression in TCL and serum
estrogen level were not significantly different in the case group compared to the
control group (P = 0.79 and P = 0.88, respectively). Also, there was no
correlation between ER expression or serum estrogen level and electrodiagnostic
parameters or Boston score. CONCLUSIONS: Sex hormones cannot still be considered
as the etiology of idiopathic CTS in postmenopausal women. The role of other
factors such as wrist ratio and narrower outlet in females compared to the males
should be considered along with hormonal changes.
PMID- 27617243
TI - Age at Natural Menopause and Related Factors in Isfahan, Iran.
AB - OBJECTIVE: This study was aimed to evaluate the age at natural menopause and
related factors among women in a population based study in 2015 in Isfahan,
Islamic Republic of Iran. METHODS: In this cross-sectional study 960 menopausal
women were selected by cluster sampling. Demographic, socioeconomic, lifestyle
behavior and reproductive history aspects were collected using a structured
questionnaire. Woman and her husband's educational level and occupation with
family income were the variables to construct socioeconomic status using
principal component analysis. RESULTS: Mean and median of natural menopause age
were 48.66 and 48 years, respectively. Women body mass index (BMI) more than 30
kg/m(2) had significantly higher menopausal age than women with lower BMI (P
value = 0.022). The mean of menopausal age was not statistically significant in
regard to marital status, physical activity, smoking status, menarche age, age at
first pregnancy and history of abortion. Menopause age with pregnancy numbers and
age at last pregnancy had a significant positive association. Women with better
socioeconomic status had significantly higher natural menopause age. Multiple
linear regression shows significant relationship between lower age at menopause
with higher age at marriage, higher number of pregnancy and lower socioeconomic
status. CONCLUSION: Age at menopause in our studied sample is similar to previous
estimates reported for other Iranian populations. Age at marriage, higher number
of pregnancy and lower socioeconomic status were the significant factors in
relations to age at menopause.
PMID- 27617244
TI - Clinical Consideration of Treatment to Ablate Uterine Fibroids with Magnetic
Resonance Imaging-guided High Intensity Focused Ultrasound (MRgFUS): Sonalleve.
AB - OBJECTIVES: Magnetic resonance imaging (MRI)-guided high intensity focused
ultrasound surgery (MRgFUS) is a newly emerging non-invasive technique for the
treatment of uterine fibroids. The purpose of this study is to review the
clinical impact of MRgFUS. METHODS: This study examined 157 patients. The high
intensity focused ultrasound (HIFU) utilized in this study was Philips Achieva
1.5 Tesla MR (Philips Healthcare, Best, the Netherlands) and Sonalleve HIFU
system. The patients were followed in post-operative Month 1, Month 3, and Month
6 to investigate any change. Then, these were further classified according to the
use of uterine stimulant (oxytocin) in parallel, Funaki Type of uterine fibroid,
HIFU intensity, and non-perfused volume (NPV) ratio. RESULTS: When the uterine
stimulant was utilized, the HIFU intensity was measured at significantly lower
levels, compared with the group not using uterine stimulant, and treatment
duration was significantly. The NPV ratio was found significantly higher in the
group using uterine stimulant. Concerning the correlation between Funaki Type of
uterine fibroid and average sonication power, it was found that the closer to
Type I, the lower the sonication power, the shorter the treatment duration, and
the higher the NPV ratio significantly. CONCLUSIONS: In this study, it was found
that the lower the Funaki Types of uterine fibroids, and the higher the NPV ratio
immediately after the operation, the larger the uterine fibroid volume decrease
and SSS change were. Also, if uterine stimulant was used in parallel in
treatment, treatment duration and HIFU intensity could become shorter and lower.
PMID- 27617246
TI - Torsion of Collision Tumor: Dermoid Cyst and Fibrothecoma with Postmenopausal
Bleeding.
AB - The term collision tumor refers to the coexistence of two adjacent but
histological distinct tumors with no histological admixture at the interface.
Collision tumors involving ovaries are extremely rare. A collision tumor composed
of a dermoid cyst and fibrothecoma is extremely rare in menopausal women. The
mechanism of the development of collision tumor is uncertain. During clinical
evaluation, differentiation of characters of these ovarian tumors is important to
decide appropriate treatment strategies and for good prognosis. We report an
unusual clinical manifestation of the torsion of a dermoid cyst and fibrothecoma
in the right ovary with postmenopausal bleeding.
PMID- 27617245
TI - Quality of Life among Iranian Infertile Women in Postmenopausal Period: A Cross
sectional Study.
AB - OBJECTIVES: Infertility has a significant impact on a women's quality of life
(QOL). Infertile women face with physical and mental challenges during their
postmenopausal period. Therefore, the present study aimed to evaluate the QOL
among Iranian infertile women in the postmenopausal period using a valid and
reliable instrument. METHODS: In this cross-sectional study both snowball and
social networking methods were used for sampling. Two demographic and QOL
questionnaire were used for data collection. The QOL questionnaire includes 41
items which measure the QOL in five dimensions: socioeconomic, mental health,
religiousness, physical health and future imagining. Data analyzed was carried
out in IBM SPSS ver. 20.0 using descriptive statistic, chi(2) test, and Fisher
test. A P value of 0.01 or less was considered significant. RESULTS: Overall 211
eligible participants were studied. Some participants obtained full score on
socioeconomic, religiousness, physical health and future imagining dimensions of
QOL but none on the mental health dimension of the QOL. Only, 6.6% of study
participants have a good QOL. There was a significant relationship between age
and financial provider whit status of QOL. CONCLUSION: Most Iranian infertile
women in the postmenopausal period have poor or moderate QOL. Therefore,
improving the QOL among these women should be considered.
PMID- 27617247
TI - Vulvar Abscess Caused by Methicillin-resistant Staphylococcus Aureus (MRSA) in a
Postmenopausal Woman.
AB - Infections of the vulva can present a complex differential to the gynecologist,
ranging from superficial skin infections to lifethreatening necrotizing
fasciitis. Recognition and timely treatment remain universal to skin and soft
tissue infections as the subcutaneous anatomy of the vulva can facilitate rapid
spread to other tissues with significant morbidity and mortality. Employing a
multidisciplinary team approach to care for vulvar cellulitis and abscess can
guide treatment from antibiotic therapies to more aggressive surgical
debridement. In this report, we describe a case of vulvar abscess caused by
Methicillin-resistant staphylococcus aureus (MRSA) in a postmenopausal woman with
underlying diseases of bronchiectasis and atelectasis.
PMID- 27617248
TI - Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report.
AB - Endometrial cancer is the most common gynecologic malignancy in developed
countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely
occurs in the endometrium; it accounts for less than 3% of all endometrial
cancers. It is presumed that clear cell carcinomas are of Mullerian duct origin,
and an association with exposure to diethylstilbestrol (DES) or other
nonsteroidal follicle stimulating hormones has been described. We report a case
of a postmenopausal woman who presented with vaginal bleeding without a specific
medical history. Under the impression of an endometrial mass, we performed a
laparoscopic operation. Pathologic results showed clear cell carcinoma of the
endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and
the rectal shelf mass was clear cell carcinoma. We report the case with a brief
review of the relevant literature.
PMID- 27617249
TI - Is focused parathyroidectomy appropriate for patients with primary
hyperparathyroidism?
AB - PURPOSE: The aim of this study was to determine whether focused or complete
parathyroidectomy was more appropriate and to compare follow-up data in primary
hyperparathyroidism (PHPT). METHODS: We retrospectively analyzed 225 operations
for PHPT at Yonsei University Health System between 2000 and 2012. After
excluding 93 patients, the remaining 132 were divided into 2 groups: those who
underwent focused parathyroidectomy (FP) and those who underwent conventional
parathyroidectomy (CP). We compared clinicopathological features; preoperative
calcium, parathyroid hormone (PTH), phosphorus, vitamin D, 24-hour urine calcium,
and alkaline phosphatase levels; postoperative calcium and PTH levels; pathologic
diagnosis; multiplicity; and results of a localization study between the 2
groups. RESULTS: There was no significant difference in the rates of development
of postoperative persistent hyperparathyroidism (1/122 FP patients and 1/10 CP
patients) between the 2 groups due to a technical reason (FP 0.8% vs. CP 10.0%, P
= 0.146). Multiglandular disease (MGD) was uncommon in all cases (6 of 132,
4.5%). All MGD cases were diagnosed using a preoperative localization study.
Sestamibi scan and ultrasonography sensitivity were 94.2% and 90.2%,
respectively. CONCLUSION: We suggest that FP is appropriate in PHPT, except in
cases of MGD if detected before the operation using preoperative imaging.
Knowledge of hereditary PHPT and improved preoperative localization studies, such
as high-resolution ultrasonography, contributed to the decision to perform FP
rather than CP in all cases of unilateral results of the localizing study.
PMID- 27617250
TI - Prognostic factors after hepatic resection for the single hepatocellular
carcinoma larger than 5 cm.
AB - PURPOSE: This study aimed to determine which factors affect the prognosis of
hepatectomy for hepatocellular carcinoma (HCC) larger than 5 cm, including the
prognostic difference between tumor sizes from 5-10 cm and larger than 10 cm.
METHODS: The medical records of 114 patients who underwent hepatectomy for single
HCC larger than 5 cm were reviewed and analyzed retrospectively. RESULTS: In the
analysis of the entire cohort of 114 patients, the 5-year overall and diseases
free survival rates were 50% and 29%, respectively. In a comparison of survival
rates between groups, tumor sizes of 5 to 10 cm and larger than 10 cm, the
overall and disease-free survival rates were not significantly different,
respectively (54% vs. 41%, P = 0.433 and 33% vs. 23%, P = 0.083). On multivariate
analysis, positive hepatitis B, high prothrombin induced by vitamin K absence or
antagonist-II levels over 200 mIU/mL, and vascular invasion (micro- and
macrovascular invasion) were independent prognostic factors for recurrence after
hepatic resection. However, tumor size larger than 10 cm was not significant for
recurrence after resection. CONCLUSION: This study shows that surgical resection
of solitary HCC larger than 5 cm showed favorable overall survival. And there is
no survival difference with tumors between 5-10 cm and larger than 10 cm.
PMID- 27617251
TI - A comparison between two methods for tumor localization during totally
laparoscopic distal gastrectomy in patients with gastric cancer.
AB - PURPOSE: The aim of this study was to compare two methods of tumor localization
during totally laparoscopic distal gastrectomy (TLDG) in patients with gastric
cancer. METHODS: From March 2014 to November 2014, patients in whom TLDG had been
engaged for middle third gastric cancer enrolled in this study. The patients were
allocated to either the radiography or endoscopy group based on the type of tumor
localization technique. Clinicopathologic outcomes were compared between the 2
groups. RESULTS: The accrual was suspended in November 2014 when 39 patients had
been enrolled because a failed localization happened in the radiography group.
The radiography and endoscopy groups included 17 (43.6 %) and 22 patients (56.4
%), respectively. Mean length of the proximal resection margin did not differ
between the radiography and endoscopy groups (4.0 +/- 2.6 and 2.8 +/- 1.2 cm,
respectively; P = 0.077). Mean localization time was longer in the radiography
group than in the endoscopy group (22.7 +/- 11.4 and 6.9 +/- 1.8 minutes,
respectively, P < 0.001). There were no statistically significant differences in
the incidence of severe complications between the 2 groups (5.9% and 4.5%,
respectively, P = 0.851). CONCLUSION: As an intraoperative tumor localization for
TLDG, radiologic method was unsafe even though other comparable parameters were
not different from that of endoscopy group. Moreover, intraoperative endoscopic
localization may be advantageous because it is highly accurate and contributes to
reducing operation time.
PMID- 27617252
TI - Risk factors for lymph node metastasis in mucosal gastric cancer and re
evaluation of endoscopic submucosal dissection.
AB - PURPOSE: The selection of the appropriate treatment strategy for patients with
mucosal gastric cancer (MGC) remains controversial. In the present study, we
aimed to determine the risk factors for lymph node (LN) metastasis in MGC and
reassess the role of endoscopic submucosal dissection (ESD). METHODS: We examined
1,191 MGC patients who underwent curative gastrectomy between January 2005 and
December 2014. We determined the clinicopathologic risk factors for LN metastasis
among the MGC patients. RESULTS: Among 1,191 patients with MGC, 42 patients
(3.5%) had LN metastasis. Univariate analysis indicated that age <= 50 years (P =
0.045), tumor invasion to the muscularis mucosa (P < 0.001), tumor size > 2 cm (P
= 0.014), presence of ulceration (P = 0.01), diffuse type as per Lauren
classification (P = 0.005), and undifferentiated-type histology (P = 0.001) were
associated with LN metastasis. Moreover, multivariate analysis indicated that
tumor invasion to the muscularis mucosa (P = 0.001; odds ratio [OR], 4.909),
presence of ulceration (P = 0.036; OR, 1.982), and undifferentiated-type
histology (P = 0.025; OR, 4.233) were independent risk factors for LN metastasis.
In particular, LN metastasis was observed in some MGC cases with indications for
ESD, including absolute indications (1 of 179, 0.6%) and expanded indications (9
of 493, 1.8%). CONCLUSION: Although MGC patients can be treated via ESD, we
recommend that they undergo a more aggressive treatment strategy if they have
tumor invasion to the muscularis mucosa, ulceration, or undifferentiated-type
histology in the final pathology report.
PMID- 27617253
TI - Use of fibrin glue in preventing pseudorecurrence after laparoscopic total
extraperitoneal repair of large indirect inguinal hernia.
AB - PURPOSE: Seroma is among the most common complications of laparoscopic total
extraperitoneal (TEP) for especially large indirect inguinal hernia, and may be
regarded as a recurrence by some patients. A potential area localized behind the
mesh and extending from the inguinal cord into the scrotum may be one of the
major etiological factors of this complication. Our aim is to describe a novel
technique in preventing pseudorecurrence by using fibrin sealant to close that
potential dead space. METHODS: Forty male patients who underwent laparoscopic TEP
for indirect inguinal hernia with at least 100-mL volume were included in this
prospective clinical study. While fibrin sealant was used to close the potential
dead space in the study group, nothing was used in the control group. The volume
of postoperative fluid collection on ultrasound was compared between the groups.
RESULTS: Patient characteristics and the volumes of hernia sac were similar
between the 2 groups. The mean volume of postoperative fluid collection was found
as 120.2 mL in the control group and 53.7 mL in the study group, indicating a
statistical significance (P < 0.001). CONCLUSION: Minimizing the potential dead
space with a fibrin sealant can reduce the amount of postoperative fluid
collection, namely the incidence of pseudorecurrence.
PMID- 27617254
TI - Evaluation of postoperative lymphocele according to amounts and symptoms by using
3-dimensional CT volumetry in kidney transplant recipients.
AB - PURPOSE: To analyze the risk factors for postoperative lymphocele, for predicting
and preventing complications. METHODS: We evaluated 92 kidney transplant
recipients with multidetector CT (MDCT) at 1-month posttransplantation. From
admission and 1-month postoperative records, data including diabetes, dialysis
type, immunosuppressant use, steroid pulse therapy, and transplantation side were
collected. Lymphocele volume was measured with 3-dimensional reconstructed,
nonenhanced MDCT at one month postoperatively. The correlations between risk
factors and lymphocele volume and between risk factors and symptomatic lymphocele
(SyL) were analyzed. The cutoff was calculated by using the receiver operating
characteristic (ROC) curve for SyL volume. RESULTS: Among 92 recipients, the mean
volume was 44.53 +/- 176.43 cm(3) and 12 had SyL. Univariable analysis between
risk factors and lymphocele volume indicated that donor age, retransplantation,
and inferiorly located lymphocele were statistically significant. The ROC curve
for SyL showed that 33.20 cm(3) was the cutoff, with 83.3% sensitivity and 93.7%
specificity. On univariable analysis between risk factors and SyL, steroid pulse,
inferiorly located lymphocele, and >33.20 cm(3) were statistically significant.
Multivariable analysis indicated that steroid pulse, >33.20 cm(3), and serum
creatinine level at one month were significant factors. CONCLUSION: Risk factors
including donor age, retransplantation, steroid pulse therapy, and inferiorly
located lymphocele are important predictors of large lymphoceles or SyL. In high
risk recipients, careful monitoring of renal function and early image
surveillance such as CT or ultrasound are recommended. If the asymptomatic
lymphocele is >33.20 cm(3) or located inferiorly, early interventions can be
considered while carefully observing the changes in symptoms.
PMID- 27617255
TI - Self expandable stent application to prevent limb occlusion in external iliac
artery during endovascular aneurysm repair.
AB - PURPOSE: Iliac extension of stent-graft during endovascular aneurysm repair
(EVAR) increases the incidence of limb occlusion (LO). Hypothetically, adjunctive
iliac stent (AIS) could offer some additional protection to overcome this
anatomic hostility. But still there is no consensus in terms of effective stent
characteristics or configuration. We retrospectively reviewed our center's
experience to offer a possible answer to this question. METHODS: Our study
included 30 patients (38 limbs) with AIS placed in the external iliac artery
(EIA) from January 2010 to December 2013. We classified iliac tortuosity based on
anatomic characteristics. AIS's were deployed in EIA with a minimum 5-mm stick
out configuration from the distal edge of the stent-graft. RESULTS: According to
the iliac artery tortuosity index, grade 0, grade 1, and grade 2 were 5 (13.2%),
30 (78.9%), and 3 (7.9%), respectively. The diameter of all AIS was 12 mm, which
was as large as or larger than the diameter of the stent-graft distal limb. SMART
stents were preferred in 34 limbs (89.5%) and stents with 60-mm length were
usually used (89.5%). During a mean follow-up of 9.13 +/- 10.78 months, ischemic
limb pain, which could be the sign of LO, was not noticed in any patients. There
was no fracture, kinking, migration, in-stent restenosis, or occlusion of AIS.
CONCLUSION: The installation of AIS after extension of stent-graft to EIA reduced
the risk of LO without any complications. AIS should be considered as a
preventive procedure of LO if stent-graft needs to be extended to EIA during
EVAR.
PMID- 27617256
TI - Recurrent hyperparathyroidism due to proliferation of autotransplanted
parathyroid tissue in a multiple endocrine neoplasia type 2A patient.
AB - About 20%-30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is
accompanied by primary hyperparathyroidism. These patients undergo
parathyroidectomy and, if needed, autotransplantation. In rare cases,
autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure
of transplantation or hyperparathyroidism due to proliferation of the
transplanted tissue. A 68-year-old female with MEN 2A underwent left
adrenalectomy for pheochromocytoma 15 years prior to presentation and total
thyroidectomy, central and right lateral neck lymph node dissection, and subtotal
parathyroidectomy with autotransplantation for medullary thyroid cancer and
primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid
adenoma was detected in the left sternocleidomastoid muscle on ultrasonography
and on an additional sestamibi scan. The mass was excised and histologically
confirmed as parathyroid adenoma. This is a very rare case, and it suggests that
long-term regular monitoring of serum calcium and intact parathyroid hormone
levels is necessary after parathyroid autotransplantation.
PMID- 27617257
TI - Celiac axis stenosis as a rare but critical condition treated with
pancreatoduodenectomy: report of 2 cases.
AB - We describe 2 cases of patients with loss of hepatic arterial flow during surgery
for pancreatic head cancer due to celiac stenosis caused by median arcuate
ligament compression. The first case underwent pylorus-resecting
pancreatoduodenectomy for pancreatic head cancer. After resection of the
gastroduodenal artery, flow in the common hepatic artery disappeared, and celiac
axis stenosis was identified. Interventional stent insertion was attempted,
however, it failed due to the acute angle of the celiac orifice (os). This
problem was resolved by arterial reconstruction. The second case underwent
pylorus-preserving pancreatoduodenectomy for pancreatic head cancer and the same
phenomenon occurred during the procedure. Interventional stent insertion was also
tried; in this patient, however, it failed due to the acute angle of the celiac
os. The problem was resolved by changing a femoral approach to a brachial
approach, and the stent was inserted into the celiac os successfully.
PMID- 27617258
TI - Analysis of morbidity, mortality, and risk factors of tracheostomy-related
complications in patients with oral and maxillofacial cancer.
AB - BACKGROUND: This study aimed to analyze and describe the morbidity and mortality
associated with tracheostomy in patients with oral cancer and to identify the
risk factors associated with tracheostomy complications. METHODS: We performed a
retrospective chart review of patients who underwent tracheostomy during a major
oral cancer resection between March 2001 and January 2016 at the National Cancer
Center, Korea. Overall, we included 51 patients who underwent tracheostomy after
oral cancer surgery. We assessed the morbidity and mortality of tracheostomy and
determined the risks associated with tracheostomy complications. RESULTS: Twenty
two tracheostomy-related complications occurred in 51 patients. The morbidity and
mortality rates were 35.2 % (n = 18) and 0 % (n = 0), respectively. Tracheostomy
related complications were tracheitis (n = 4), obstructed tracheostomy (n = 9),
displaced tracheostomy (n = 5), air leakage (n = 1), stomal dehiscence (n = 1),
and decannulation failure (n = 2). Most complications (19/22) occurred during the
early postoperative period. Considering the risk factors for tracheostomy
complications, the type of tube used was associated with the occurrence of
tracheitis (p < 0.05). Additionally, body mass index and smoking status were
associated with tube displacement (p < 0.05). However, no risk factors were
significantly associated with obstructed tracheostomy. CONCLUSIONS: Patients with
risk factors for tracheostomy complications should be carefully observed during
the early postoperative period by well-trained medical staff.
PMID- 27617259
TI - An Old Solution for a New Problem: Antiserum against Emerging Infectious
Diseases.
PMID- 27617260
TI - Towards Profiles of Resistance Development and Toxicity for the Small Cationic
Hexapeptide RWRWRW-NH2.
AB - RWRWRW-NH2 (MP196) is an amphipathic hexapeptide that targets the bacterial
cytoplasmic membrane and inhibits cellular respiration and cell wall synthesis.
In previous studies it showed promising activity against Gram-positive bacteria
and no significant cytotoxicity or hemolysis. MP196 is therefore used as lead
structure for developing more potent antibiotic derivatives. Here we present a
more comprehensive study on the parent peptide MP196 with regard to clinically
relevant parameters. We found that MP196 acts rapidly bactericidal killing 97% of
initial CFU within 10 min at two times MIC. We were unable to detect resistance
in standard 24 and 48 h resistance frequency assays. However, MP196 was effective
against some but not all MRSA and VISA strains. Serum binding of MP196 was
intermediate and we confirmed its low toxicity against mammalian cell lines.
MP196 did neither induce NFkappaB activation nor cause an increase in IL8 levels
at 250 MUg/mL, and no IgE-dependent activation of basophil granulocytes was
detected at 500 MUg/mL. Yet, MP196 demonstrated acute toxicity in mice upon
injection into the blood stream. Phase contrast microscopy of mouse blood treated
with MP196 revealed a shrinking of erythrocytes at 250 MUg/mL and severe
morphological changes and lysis of erythrocytes at 500 MUg/mL. These data suggest
that MP196 derivatization directed at further lowering hemolysis could be
instrumental in overcoming acute toxicity. The assessment of hemolysis is a
critical step in the evaluation of the clinical potential of promising
antimicrobial peptides and should be accompanied by microscopy-based
morphological analysis of blood cells.
PMID- 27617261
TI - Potential Impact of Dietary Choices on Phosphorus Recycling and Global Phosphorus
Footprints: The Case of the Average Australian City.
AB - Changes in human diets, population increases, farming practices, and globalized
food chains have led to dramatic increases in the demand for phosphorus
fertilizers. Long-term food security and water quality are, however, threatened
by such increased phosphorus consumption, because the world's main source,
phosphate rock, is an increasingly scarce resource. At the same time, losses of
phosphorus from farms and cities have caused widespread water pollution. As one
of the major factors contributing to increased phosphorus demand, dietary choices
can play a key role in changing our resource consumption pathway. Importantly,
the effects of dietary choices on phosphorus management are twofold: First,
dietary choices affect a person or region's "phosphorus footprint" - the
magnitude of mined phosphate required to meet food demand. Second, dietary
choices affect the magnitude of phosphorus content in human excreta and hence the
recycling- and pollution-potential of phosphorus in sanitation systems. When
considering options and impacts of interventions at the city scale (e.g.,
potential for recycling), dietary changes may be undervalued as a solution toward
phosphorus sustainability. For example, in an average Australian city, a
vegetable-based diet could marginally increase phosphorus in human excreta (an 8%
increase). However, such a shift could simultaneously dramatically decrease the
mined phosphate required to meet the city resident's annual food demand by 72%.
Taking a multi-scalar perspective is therefore key to fully exploring dietary
choices as one of the tools for sustainable phosphorus management.
PMID- 27617262
TI - Cancer Stem Cells in Glioblastoma Multiforme.
AB - AIM: To identify and characterize cancer stem cells (CSC) in glioblastoma
multiforme (GBM). METHODS: Four-micrometer thick formalin-fixed paraffin-embedded
GBM samples from six patients underwent 3,3-diaminobenzidine (DAB) and
immunofluorescent (IF) immunohistochemical (IHC) staining for the embryonic stem
cell (ESC) markers NANOG, OCT4, SALL4, SOX2, and pSTAT3. IF IHC staining was
performed to demonstrate co-expression of these markers with GFAP. The protein
expression and the transcriptional activities of the genes encoding NANOG, OCT4,
SOX2, SALL4, and STAT3 were investigated using Western blotting (WB) and
NanoString gene expression analysis, respectively. RESULTS: DAB and IF IHC
staining demonstrated the presence of a CSC population expressing NANOG, OCT4,
SOX2, SALL4, and pSTAT3 with the almost ubiquitous presence of SOX2 and a
relatively low abundance of OCT4, within GBM. The expression of NANOG, SOX2 and,
pSTAT3 but, not OCT and SALL4, was confirmed by WB. NanoString gene analysis
demonstrated transcriptional activation of NANOG, OCT4, SALL4, STAT3, and SOX2 in
GBM. CONCLUSION: This study demonstrated a population of CSCs within GBM
characterized by the expression of the CSC markers NANOG, SALL4, SOX2, pSTAT3 and
OCT4 at the protein and mRNA levels. The almost ubiquitous presence of SOX2 and a
relatively low abundance of OCT4 would support the putative existence of a stem
cell hierarchy within GBM.
PMID- 27617264
TI - Evaporative edge lithography of a liposomal drug microarray for cell migration
assays.
AB - Lipid multilayer microarrays are a promising approach to miniaturize laboratory
procedures by taking advantage of the microscopic compartmentalization
capabilities of lipids. Here, we demonstrate a new method to pattern lipid
multilayers on surfaces based on solvent evaporation along the edge where a
stencil contacts a surface called evaporative edge lithography (EEL). As an
example of an application of this process, we use EEL to make microarrays
suitable for a cell-based migration assay. Currently existing cell migration
assays require a separate compartment for each drug which is dissolved at a
single concentration in solution. An advantage of the lipid multilayer microarray
assay is that multiple compounds can be tested on the same surface. We
demonstrate this by testing the effect of two different lipophilic drugs, Taxol
and Brefeldin A, on collective cell migration into an unpopulated area. This
particular assay should be scalable to test of 2000 different lipophilic
compounds or dosages on a standard microtiter plate area, or if adapted for
individual cell migration, it would allow for high-throughput screening of more
than 50,000 compounds per plate.
PMID- 27617263
TI - The Role of Genetic Testing in the Identification of Young Athletes with
Inherited Primitive Cardiac Disorders at Risk of Exercise Sudden Death.
AB - Although relatively rare, inherited primitive cardiac disorders (IPCDs) in
athletes have a deep social impact since they often present as sudden cardiac
death (SCD) of young and otherwise healthy persons. The diagnosis of these
conditions is likely underestimated due to the lack of shared clinical criteria
and to the existence of several borderline clinical pictures. We will focus on
the clinical and molecular diagnosis of the most common IPCDs, namely
hypertrophic cardiomyopathies, long QT syndrome, arrhythmogenic right ventricular
cardiomyopathy, and left ventricular non-compaction. Collectively, these
conditions account for the majority of SCD episodes and/or cardiologic clinical
problems in athletes. In addition to the clinical and instrumental tools for the
diagnosis of IPCD, the viral technological advances in genetic testing have
facilitated the molecular confirmation of these conditions. However, genetic
testing presents several issues: the limited sensitivity (globally, around 50%),
the low prognostic predictive value, the probability to find pathogenic variants
in different genes in the same patient, and the risk of non-interpretable
results. In this review, we will analyze the pros and cons of the different
clinical approaches for the presymptomatic identification, the diagnosis and
management of IPCD athletes, and we will discuss the indications to the genetic
testing for patients and their relatives, particularly focusing on the most
complex scenarios, such as presymptomatic tests, uncertain results, and
unexpected findings.
PMID- 27617266
TI - Scleral resection in chronic central serous chorioretinopathy complicated by
exudative retinal detachment.
AB - BACKGROUND: Effective therapeutic options are limited for the management of
chronic central serous chorioretinopathy (CSCR) complicated by exudative retinal
detachments (RD). The authors describe the resolution of one such case following
partial thickness scleral resection with mitomycin C. CASE PRESENTATION: This 39
year-old male presented with a unilateral inferior exudative RD in the right eye.
There was no history of steroid use either locally or systemically. The fundus
fluorescein angiogram showed window defects and leaks typical of chronic CSCR.
The axial length was 21.06 mm in the right eye and 21 mm in the left eye.
Thickening of the ocular coats was evident on ocular ultrasound. Considering an
axial length in the borderline-low range inferotemporal and inferonasal partial
thickness scleral resection with mitomycin C was performed. The exudative RD
resolved at 4 months. CONCLUSION: Partial thickness scleral resection may be
considered as an option for treating chronic CSCR patients with borderline-low
axial length complicated by exudative RD.
PMID- 27617267
TI - Osteosarcoma: mouse models, cell of origin and cancer stem cell.
AB - Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in
children and adults. High-dose cytotoxic chemotherapy and surgical resection have
improved prognosis, with long-term survival for non-metastatic disease
approaching 70%. However, most OS tumors are high grade and tend to rapidly
develop pulmonary metastases. Despite clinical advances, patients with metastatic
disease or relapse have a poor prognosis. Here the cell biology of OS is reviewed
with a special emphasis on mouse models as well as the roles of the cell of
origin and cancer stem cells. A better understanding of the molecular
pathogenesis of human OS is essential for the development of improved prognostic
and diagnostic markers as well as targeted therapies for both primary and
metastatic OS.
PMID- 27617265
TI - Pregnane X Receptor and Cancer: Context-Specificity is Key.
AB - Pregnane X receptor (PXR) is an adopted orphan nuclear receptor that is activated
by a wide-range of endobiotics and xenobiotics, including chemotherapy drugs. PXR
plays a major role in the metabolism and clearance of xenobiotics and endobiotics
in liver and intestine via induction of drug-metabolizing enzymes and drug
transporting proteins. However, PXR is expressed in several cancer tissues and
the accumulating evidence strongly points to the differential role of PXR in
cancer growth and progression as well as in chemotherapy outcome. In cancer
cells, besides regulating the gene expression of enzymes and proteins involved in
drug metabolism and transport, PXR also regulates other genes involved in
proliferation, metastasis, apoptosis, anti-apoptosis, inflammation, and oxidative
stress. In this review, we focus on the differential role of PXR in a variety of
cancers, including prostate, breast, ovarian, endometrial, and colon. We also
discuss the future directions to further understand the differential role of PXR
in cancer, and conclude with the need to identify novel selective PXR modulators
to target PXR in PXR-expressing cancers.
PMID- 27617269
TI - Clinicopathological Correlates in a PRNP P102L Mutation Carrier with Rapidly
Progressing Parkinsonism-dystonia.
AB - Parkinsonism-dystonia is rare in carriers of PRNP P102L mutation. Severity and
distribution of prion protein (PrP) deposition may influence the clinical
presentation. We present such clinic-pathological correlation in a 56-year-old
male with a PRNP P102L mutation associated with a phenotype characterized by
rapidly progressing parkinsonism-dystonia. The patient was studied clinically
(videotaped exams, brain MRIs); molecular genetically (gene sequence analysis);
and neuropathologically (histology, immunohistochemistry) during his 7-month
disease course. The patient had parkinsonism, apraxia, aphasia, and dystonia,
which progressed rapidly. Molecular genetic analysis revealed PRNP P102L mutation
carrier status. Brain MRIs revealed progressive global volume loss and T2/FLAIR
hyperintensity in neocortex and basal ganglia. Postmortem examination showed
neuronal loss, gliosis, spongiform changes, and PrP deposition in the striatum.
PrP immunohistochemistry revealed widespread severe PrP deposition in the
thalamus and cerebellar cortex. Based on the neuropathological and molecular
genetic analysis, the rapidly progressing parkinsonism-dystonia correlated with
nigrostriatal, thalamic, and cerebellar pathology.
PMID- 27617268
TI - Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African
adults.
AB - We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could
complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy
focuses vaccine-elicited effector T-cells on functionally and structurally
conserved regions (not full-length proteins and not only epitopes) of the HIV-1
proteome, which are common to most global variants and which, if mutated, cause a
replicative fitness loss. Our first clinical trial in low risk HIV-1-negative
adults in Oxford demonstrated the principle that naturally mostly subdominant
epitopes, when taken out of the context of full-length proteins/virus and
delivered by potent regimens involving combinations of simian adenovirus and
poxvirus modified vaccinia virus Ankara, can induce robust CD8(+) T cells of
broad specificities and functions capable of inhibiting in vitro HIV-1
replication. Here and for the first time, we tested this strategy in low risk HIV
1-negative adults in Africa. We showed that the vaccines were well tolerated and
induced high frequencies of broadly HIVconsv-specific plurifunctional T cells,
which inhibited in vitro viruses from four major clades A, B, C, and D. Because
sub-Saharan Africa is globally the region most affected by HIV-1/AIDS, trial HIV
CORE 004 represents an important stage in the path toward efficacy evaluation of
this highly rational and promising vaccine strategy.
PMID- 27617270
TI - Deep Brain Stimulation Battery Longevity: Comparison of Monopolar Versus Bipolar
Stimulation Modes.
AB - BACKGROUND: Deep brain stimulation is an effective treatment for movement
disorders, but it is relatively complex, invasive, and costly. Little is known
about whether stimulation mode alters pulse generator (battery) longevity in
routine clinical care. OBJECTIVE: To compare battery longevity during monopolar
versus bipolar stimulation in patients who underwent deep brain stimulation for
movement disorders. METHODS: We evaluated 2,902 programming adjustments and
calculated the average stimulator settings for 393 batteries in 200 unique
patients with Parkinson's disease and essential tremor. We classified the pulse
generators into different stimulation modes (monopolar, bipolar, tripolar, double
monopolar) and compared battery longevity with Kaplan Meier survival analyses
using the log rank test. We exclusively implanted the Medtronic 3387 lead with
adjacent electrode contacts separated by 1.5 mm. RESULTS: The mean pulse
generator longevity was 47.6+/-1.6 months regardless of diagnosis or stimulation
mode. Bipolar stimulation mode was associated with greater longevity than
monopolar stimulation (56.1+/-3.4 versus 44.2+/-2.1 months, p=0.006). This effect
was most pronounced when stimulation parameters were at low to moderate intensity
settings. Double monopolar configuration was associated with less pulse generator
longevity than conventional stimulation modes (37.8+/-5.6 versus 49.7+/-1.9,
p=0.014). CONCLUSION: IPGs initially programmed in bipolar mode provided one year
of additional battery longevity versus monopolar mode in this large retrospective
series of patients with essential tremor and Parkinson's disease. Given
satisfactory efficacy for motor symptoms, bipolar stimulation mode is a feasible
alternative programming strategy at the initiation of DBS therapy.
PMID- 27617271
TI - In vitro Real-time Measurement of the Intra-bacterial Redox Potential.
AB - All bacteria that live in oxygenated environments have to deal with oxidative
stress caused by some form of exogenous or endogenous reactive oxygen species
(ROS) (Imlay, 2013). Large quantities of ROS damage DNA, lipids and proteins
which can eventually lead to bacterial cell death (Imlay, 2013). In contrast,
smaller quantities of ROS can play more sophisticated roles in cellular
signalling pathways affecting almost every process in the bacterial cell e.g.
metabolism, stress responses, transcription, protein synthesis, etc. Previously,
inadequate analytical methods prevented appropriate analysis of the intra
bacterial redox potential. Herein, we describe a method for the measurement of
real-time changes to the intra-bacterial redox potential using redox-sensitive
GFP (roGFP2) (van der Heijden et al., 2015). The roGFP2 protein is engineered to
contain specific cysteine residues that form an internal disulfide bridge upon
oxidation which results in a slight shift in protein conformation (Hanson et al.,
2004). This shift results in two distinct protein isoforms with different
fluorescence excitation spectra after excitation at 405 nm and 480 nm
respectively. Consequently, the corresponding 405/480 nm ratio can be used as a
measure for the intra-bacterial redox potential. The ratio-metric analysis
excludes variations due to differences in roGFP2 concentrations and since the
conformational shift is reversible the system allows for measurement of oxidizing
as well as reducing conditions. In this protocol we describe the system by
measuring the intra-bacterial redox potential inside Salmonella typhimurium (S.
typhimurium) however this system can be adjusted for use in other Gram-negative
bacteria.
PMID- 27617272
TI - The Comorbid Influence of High Depressive Symptoms and Diabetes on Mortality and
Disability in Mexican Americans Aged 75 and Above.
AB - OBJECTIVE: To examine the individual and combined effects of depression and
diabetes on mortality and disability over 6 years among Mexican Americans aged
>=75. METHOD: The final sample included 1,785 participants from the Hispanic
Established Population for the Epidemiological Study of the Elderly. Cox
proportional hazards regression models were used to estimate the hazard ratios
for incidence for mortality and disability according to diabetes and depressive
symptoms. RESULTS: Diabetics were more likely to become activities of daily
living (ADL) disabled Hazard Ratio (HR) = 1.44, 95% confidence interval [CI] =
[1.18, 1.77]) and deceased (HR = 1.47, 95% CI = [1.24, 1.74]) compared with non
diabetics. Diabetics reporting high depressive symptomatology were more than two
times as likely to become ADL disabled and deceased compared with diabetics not
reporting high depressive symptoms. Participants with high depressive symptoms
and taking insulin alone or both oral medications and insulin were at the
greatest risk of disability (HR = 3.83, 95% CI = [1.66, 8.81]). CONCLUSION:
Diabetes increases the risk of disability and mortality, especially among Mexican
Americans with high depressive symptoms or who are taking insulin alone or both
oral medications and insulin. Interventions that are able to reduce the
prevalence of depression and diabetes are needed to limit the future burden of
disability and mortality in this population.
PMID- 27617273
TI - The Age-related Positivity Effect and Tobacco Warning Labels.
AB - OBJECTIVES: This study tested whether age is a factor in viewing time for tobacco
warning labels. The approach drew from previous work demonstrating an age-related
positivity effect, whereby older adults show preferences toward positive and away
from negative stimuli. METHODS: Participants were 295 daily smokers from
Appalachian Ohio (age range: 21-68). All participants took part in an eye
tracking paradigm that captured the attention paid to elements of health warning
labels in the context of magazine advertisements. Participants also reported on
their past cessation attempts and their beliefs about the dangers of smoking.
RESULTS: Consistent with theory on age-related positivity, older age predicted
weaker beliefs about smoking risks, but only among those with no past-year quit
attempts. In support of our primary hypothesis, older age was also related to a
lower percentage of time spent viewing tobacco warning labels, both overall (text
+ image) and for the graphic image alone. These associations remained after
controlling for cigarettes smoked per day. CONCLUSIONS: Overall, findings suggest
that age is an important consideration for the design of future graphic warning
labels and other tobacco risk communications. For older adults, warning labels
may need to be tailored to overcome the age-related positivity effect.
PMID- 27617274
TI - Functional diversity of long non-coding RNAs in immune regulation.
AB - Precise and dynamic regulation of gene expression is a key feature of immunity.
In recent years, rapid advances in transcriptome profiling analysis have led to
recognize long non-coding RNAs (lncRNAs) as an additional layer of gene
regulation context. In the immune system, lncRNAs are found to be widely
expressed in immune cells including monocytes, macrophages, dendritic cells
(DCs), neutrophils, T cells and B cells during their development, differentiation
and activation. However, the functional importance of immune-related lncRNAs is
just emerging to be characterized. In this review, we discuss the up-to-date
knowledge of lncRNAs in immune regulation.
PMID- 27617276
TI - Data on endogenous chicken sperm peptides and small proteins obtained through Top
Down High Resolution Mass Spectrometry.
AB - The endogenous peptides and small proteins present in chicken sperm were
identified in the context of the characterization of a fertility-diagnostic
method based on the use of ICM-MS (Intact Cell Matrix-Assisted Laser
Desorption/Ionization Time-of-Flight Mass Spectrometry). The interpretation and
description of these data can be found in a research article, "Intact cell MALDI
TOF MS on sperm: a molecular test for male fertility diagnosis" (Soler et al.,
2016) [1], and raw data derived from this analysis have been deposited to the
ProteomeXchange Consortium via the PRIDE partner repository with the dataset
identifier PRIDE: PXD002768. Here, we describe the inventory of all the molecular
species identified, along with their biochemical features and functional
analysis. This peptide/protein catalogue can be further employed as reference for
other studies and reveal that the use of proteomics allows for a global
evaluation of sperm cells functions.
PMID- 27617277
TI - The Akt/mTOR pathway: Data comparing young and aged mice with leucine
supplementation at the onset of skeletal muscle regeneration.
AB - The data described herein is related to the article "Differential Effects of
Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle
Regeneration" [1]. Aging is associated with a decreased ability of skeletal
muscle to regenerate following injury. Leucine supplementation has been
extensively shown, in young subjects, to promote protein synthesis during
regeneration; however, the effects of leucine supplementation on the Akt/mTOR
pathway in aged mice at the onset of muscle regeneration are not fully
elucidated. In this article, we present data on the Akt/mTOR protein synthesis
pathway at the onset of muscle regeneration in young and aged C57BL/6J mice that
are and are not receiving leucine supplementation. More specifically, protein
content of total Akt, mTOR, p70S6K and 4EBP-1 are presented. Additionally, we
provide relative (phosphorylated:total) protein content comparisons of these
targets as they present themselves in young and aged mice who have neither been
injured nor received leucine supplementation. Lastly, markers of atrophy
(FoxO1/O3, MuRF-1, Atrogin-1) are also reported in these young and aged control
groups.
PMID- 27617275
TI - Genetic Factors in Intervertebral Disc Degeneration.
AB - Low back pain (LBP) is a major cause of disability and imposes huge economic
burdens on human society worldwide. Among many factors responsible for LBP,
intervertebral disc degeneration (IDD) is the most common disorder and is a
target for intervention. The etiology of IDD is complex and its mechanism is
still not completely understood. Many factors such as aging, spine deformities
and diseases, spine injuries, and genetic factors are involved in the
pathogenesis of IDD. In this review, we will focus on the recent advances in
studies on the most promising and extensively examined genetic factors associated
with IDD in humans. A number of genetic defects have been correlated with
structural and functional changes within the intervertebral disc (IVD), which may
compromise the disc's mechanical properties and metabolic activities. These
genetic and proteomic studies have begun to shed light on the molecular basis of
IDD, suggesting that genetic factors are important contributors to the onset and
progression of IDD. By continuing to improve our understanding of the molecular
mechanisms of IDD, specific early diagnosis and more effective treatments for
this disabling disease will be possible in the future.
PMID- 27617278
TI - Summary data of potency and parameter information from semi-mechanistic PKPD
modeling of prolactin release following administration of the dopamine D2
receptor antagonists risperidone, paliperidone and remoxipride in rats.
AB - We provide the reader with relevant data related to our recently published paper,
comparing two mathematical models to describe prolactin turnover in rats
following one or two doses of the dopamine D2 receptor antagonists risperidone,
paliperidone and remoxipride, "A comparison of two semi-mechanistic models for
prolactin release and prediction of receptor occupancy following administration
of dopamine D2 receptor antagonists in rats" (Taneja et al., 2016) [1]. All
information is tabulated. Summary level data on the in vitro potencies and the
physicochemical properties is presented in Table 1. Model parameters required to
explore the precursor pool model are presented in Table 2. In Table 3, estimated
parameter comparisons for both models are presented, when separate potencies are
estimated for risperidone and paliperidone, as compared to a common potency for
both drugs. In Table 4, parameter estimates are compared when the drug effect is
parameterized in terms of drug concentration or receptor occupancy.
PMID- 27617279
TI - Dataset of SSR markers for ISSR-Suppression-PCR to detect genetic variation in
Garcinia mangostana L. in Peninsular Malaysia.
AB - In this dataset, we present 15 Simple Sequence Repeat (SSR) markers with the
motifs (AC)n, (GA)n, and (AC)n(AG)n using a ISSR-Suppression-PCR technique in
order to discriminate Garcinia mangostana from diverse geographical origins in
Peninsular Malaysia. A few loci showed differences between 3 and 6 bp in allele
size, indicating that there are some polymorphisms between individuals
correlating to the number of SSR repeats that may be useful for differentiate of
genotypes. Collectively, these data show that the ISSR-Suppression-PCR is a
valuable method to illustrate genetic variation of selected G. mangostana in
Malaysia.
PMID- 27617280
TI - Data on calcium increases depending on stretch in dystrophic cardiomyocytes.
AB - In this data article, intracellular Ca(2+) concentration ([Ca(2+)]i) was measured
in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different
conditions: at rest and during the application of an axial stretch. Using a
carbon microfibers technique, axial stretch was applied to mimic effects of
physiological conditions of ventricular filling. A study of cation entry with the
same experimental model and the manganese quenching method reported (i) a
constitutive cation entry in mdx cardiomyocytes and (ii) the involvement of TRPV2
channels in axial-stretch dependant cation entry, "Axial stretch-dependent cation
entry in dystrophic cardiomyopathy: involvement of several TRPs channels"
(Aguettaz et al., 2016) [1]. Here, the Ca(2+) dye fluo-8 was used for [Ca(2+)]i
measurement, in both resting and stretching conditions, using a perfusion
protocol starting initially with a calcium free Tyrode solution followed by the
perfusion of 1.8 mM Ca(2+) Tyrode solution. The variation of [Ca(2+)]i was found
higher in mdx cardiomyocytes.
PMID- 27617281
TI - Quantitative geospatial dataset on the near-surface heavy metal concentrations in
semi-arid soils from Maibele Airstrip North, Central Botswana.
AB - This article contains a statistically analyzed dataset of the heavy metals
including Cr, Co, Ni, Cu, Zn and Pb contents of near-surface (~30 cm depth) soils
in a Cu-Ni prospecting field at Airstrip North, Central Botswana. The soils
developed on paragneisses and amphibolites parent materials in a semi-arid
environment with hardveld vegetation, "The geology of the Topisi area" (Key et
al., 1994) [1]. Grid sampling was adopted in the field data collection. Heavy
metals were determined using the relatively new portable x-ray fluorescence
spectrometer (Delta Premium, 510,890, USA) technology in a "soil" mode. The data
presented was obtained from the average reading of two soil samples collected
from same point but passed through sieves.
PMID- 27617282
TI - Data set of phylogenetic analysis inferred based on the complete genomes of the
family Nodaviridae.
AB - In this article, nine complete genomes of viruses from the genus Alphanodavirus
and Betanodavirus (Family Nodaviridae) were comparatively analyzed and the data
of their evolutionary origins and relatedness are reported. The nucleotide
sequence alignment of the complete genomes from all species and their deduced
evolutionary relationships are presented. High sequence similarity within the
genus Betanodavirus compared to the genus Alphanodavirus was revealed in multiple
sequence alignment of the Nodaviridae genomes. The amino acid sequence similarity
for both RNA1 and RNA2 ORF is more conserved in Betanodavirus, compared to
Alphanodavirus. The conserved and variable regions within the virus genome that
were defined based on the multiple sequence alignments are presented in this
dataset.
PMID- 27617283
TI - Multiple recurrent squamous cell carcinomas and utility of anticytokeratin
immunohistochemistry.
PMID- 27617284
TI - Treatment of cystic hygroma in a young infant through multidisciplinary approach
involving sirolimus, sclerotherapy, and debulking surgery.
PMID- 27617285
TI - Pazopanib-mediated long-term disease stabilization after resection of a uterine
leiomyosarcoma metastasis to the brain: A case report.
AB - A 48-year-old woman underwent a total abdominal hysterectomy after preoperative
diagnosis of multiple uterine leiomyomas. The histopathological diagnosis was
leiomyosarcoma (LMS). After 47 months, multiple lung metastases were detected and
resected. The patient was also diagnosed with pelvic bone metastasis and received
six cycles of adjuvant chemotherapy with gemcitabine plus docetaxel and local
radiation therapy to control the pain. Seventy-seven months from the initial
diagnosis, she had a headache and developed left hemiparesis and aphasia. Imaging
studies detected a solitary brain metastasis in the right frontal lobe. The
patient underwent a craniotomy and resection of the lesion, which was a confirmed
metastasis from uterine LMS by histopathology. One month after the craniotomy,
the patient experienced lower abdominal pain, and a pelvic metastasis was
detected. She was prescribed oral pazopanib (800 mg per day). For twelve months,
she remained asymptomatic, but gradually, pelvic pain increased due to pelvic
mass growth. After 14 months of pazopanib treatment, pazopanib was discontinued.
To date, for 18 months after the brain surgery, she is alive with disease, and
the brain metastasis has not recurred.
PMID- 27617286
TI - Bevacizumab induced hypertension in gynecologic cancer: Does it resolve after
completion of therapy?
AB - Hypertension (HTN) induced by bevacizumab is a side effect that is often thought
to resolve after treatment. However, there are currently no reports on rates of
resolution. We assess the incidence and timing of the resolution of bevacizumab
induced HTN. We evaluated all patients treated with bevacizumab for gynecologic
malignancies at a single institution from 2012 through 2014. HTN was
retrospectively diagnosed and staged by CTCAE v4.0 criteria. Resolution of HTN
was defined as >= 2 values return to baseline blood pressure and/or
discontinuation/decrease of blood pressure medications. We identified 104
patients; 35 were excluded due to receiving bevacizumab at time of analysis.
Grade 2 or higher induced HTN was identified in 34/69 (49.3%) patients, of which
26/69 (37.7%) had grade 2 HTN and 8/69 (11.6%) had grade 3/4 HTN. Onset of HTN
occurred at a median of 67 (14-791) days. Resolution of HTN occurred in 28/34
(82.4%) patients with a median time to resolution of 87 (3-236) days. BMI,
history of HTN, blood pressure medications, prior bevacizumab treatment, number
of bevacizumab cycles, CA-125 and albumin at initiation of treatment were not
independent risk factors associated with developing HTN in multivariate analysis.
Median PFS for those with HTN was 12.5 (1.9-45.8) months vs 11.0 (2.1-44.7) for
those without (p = 0.17). Hypertension induced by bevacizumab resolved in 82% of
patients in a median of 87 days. There were no identifiable risk factors
associated with induced HTN and HTN was not a biomarker for improved prognosis in
our cohort.
PMID- 27617287
TI - Collapsing avian community on a Hawaiian island.
AB - The viability of many species has been jeopardized by numerous negative factors
over the centuries, but climate change is predicted to accelerate and increase
the pressure of many of these threats, leading to extinctions. The Hawaiian
honeycreepers, famous for their spectacular adaptive radiation, are predicted to
experience negative responses to climate change, given their susceptibility to
introduced disease, the strong linkage of disease distribution to climatic
conditions, and their current distribution. We document the rapid collapse of the
native avifauna on the island of Kaua'i that corresponds to changes in climate
and disease prevalence. Although multiple factors may be pressuring the
community, we suggest that a tipping point has been crossed in which temperatures
in forest habitats at high elevations have reached a threshold that facilitates
the development of avian malaria and its vector throughout these species' ranges.
Continued incursion of invasive weeds and non-native avian competitors may be
facilitated by climate change and could also contribute to declines. If current
rates of decline continue, we predict multiple extinctions in the coming decades.
Kaua'i represents an early warning for the forest bird communities on the Maui
and Hawai'i islands, as well as other species around the world that are trapped
within a climatic space that is rapidly disappearing.
PMID- 27617289
TI - Color polymorphism in an aphid is maintained by attending ants.
AB - The study of polymorphisms is particularly informative for enhancing our
understanding of phenotypic and genetic diversity. The persistence of
polymorphism in a population is generally explained by balancing selection. Color
polymorphisms that are often found in many insects and arthropods are prime
examples of the maintenance of polymorphisms via balancing selection. In some
aphids, color morphs are maintained through frequency-dependent predation by two
predatory insects. However, the presence of color polymorphism in ant-attended
aphids cannot be explained by traditional balancing selection because these
aphids are free from predation. We examined the selective advantages of the
existence of two color (red and green) morphs in the ant-attended aphid,
Macrosiphoniella yomogicola, in fields. We measured the degree of ant attendance
on aphid colonies with different proportions of color morphs. The results show
that the ants strongly favor aphid colonies with intermediate proportions of the
two color morphs. The relationship between the degree of ant attendance and the
proportion of color morphs in the field is convex when aphid colony size and ant
colony size are controlled. This function has a peak of approximately 65% of
green morphs in a colony. This system represents the first case of a balancing
polymorphism that is not maintained by opposing factors but by a symbiotic
relationship.
PMID- 27617288
TI - Portraying breast cancers with long noncoding RNAs.
AB - Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer
development, but this role is not yet clear. We performed a genome-wide
transcriptional survey to explore the lncRNA landscape across 995 breast tissue
samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast
tumors, as compared to normal samples. Unsupervised hierarchical clustering of
breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups
that correlate tightly with PAM50-defined mRNA-based subtypes. Using multivariate
analysis, we identified no less than 210 lncRNAs prognostic of clinical outcome.
By analyzing the coexpression of lncRNA genes and protein-coding genes, we
inferred potential functions of the 215 dysregulated lncRNAs. We then associated
subtype-specific lncRNAs with key molecular processes involved in cancer. A
correlation was observed, on the one hand, between luminal A-specific lncRNAs and
the activation of phosphatidylinositol 3-kinase, fibroblast growth factor, and
transforming growth factor-beta pathways and, on the other hand, between basal
like-specific lncRNAs and the activation of epidermal growth factor receptor
(EGFR)-dependent pathways and of the epithelial-to-mesenchymal transition.
Finally, we showed that a specific lncRNA, which we called CYTOR, plays a role in
breast cancer. We confirmed its predicted functions, showing that it regulates
genes involved in the EGFR/mammalian target of rapamycin pathway and is required
for cell proliferation, cell migration, and cytoskeleton organization. Overall,
our work provides the most comprehensive analyses for lncRNA in breast cancers.
Our findings suggest a wide range of biological functions associated with lncRNAs
in breast cancer and provide a foundation for functional investigations that
could lead to new therapeutic approaches.
PMID- 27617290
TI - Pattern recognition with "materials that compute".
AB - Driven by advances in materials and computer science, researchers are attempting
to design systems where the computer and material are one and the same entity.
Using theoretical and computational modeling, we design a hybrid material system
that can autonomously transduce chemical, mechanical, and electrical energy to
perform a computational task in a self-organized manner, without the need for
external electrical power sources. Each unit in this system integrates a self
oscillating gel, which undergoes the Belousov-Zhabotinsky (BZ) reaction, with an
overlaying piezoelectric (PZ) cantilever. The chemomechanical oscillations of the
BZ gels deflect the PZ layer, which consequently generates a voltage across the
material. When these BZ-PZ units are connected in series by electrical wires, the
oscillations of these units become synchronized across the network, where the
mode of synchronization depends on the polarity of the PZ. We show that the
network of coupled, synchronizing BZ-PZ oscillators can perform pattern
recognition. The "stored" patterns are set of polarities of the individual BZ-PZ
units, and the "input" patterns are coded through the initial phase of the
oscillations imposed on these units. The results of the modeling show that the
input pattern closest to the stored pattern exhibits the fastest convergence time
to stable synchronization behavior. In this way, networks of coupled BZ-PZ
oscillators achieve pattern recognition. Further, we show that the convergence
time to stable synchronization provides a robust measure of the degree of match
between the input and stored patterns. Through these studies, we establish
experimentally realizable design rules for creating "materials that compute."
PMID- 27617291
TI - Atomic-scale compositional mapping reveals Mg-rich amorphous calcium phosphate in
human dental enamel.
AB - Human dental enamel, the hardest tissue in the body, plays a vital role in
protecting teeth from wear as a result of daily grinding and chewing as well as
from chemical attack. It is well established that the mechanical strength and
fatigue resistance of dental enamel are derived from its hierarchical structure,
which consists of periodically arranged bundles of hydroxyapatite (HAP)
nanowires. However, we do not yet have a full understanding of the in vivo HAP
crystallization process that leads to this structure. Mg(2+) ions, which are
present in many biological systems, regulate HAP crystallization by stabilizing
its precursor, amorphous calcium phosphate (ACP), but their atomic-scale
distribution within HAP is unknown. We use atom probe tomography to provide the
first direct observations of an intergranular Mg-rich ACP phase between the HAP
nanowires in mature human dental enamel. We also observe Mg-rich elongated
precipitates and pockets of organic material among the HAP nanowires. These
observations support the postclassical theory of amelogenesis (that is, enamel
formation) and suggest that decay occurs via dissolution of the intergranular
phase. This information is also useful for the development of more accurate
models to describe the mechanical behavior of teeth.
PMID- 27617293
TI - Quasi-ballistic carbon nanotube array transistors with current density exceeding
Si and GaAs.
AB - Carbon nanotubes (CNTs) are tantalizing candidates for semiconductor electronics
because of their exceptional charge transport properties and one-dimensional
electrostatics. Ballistic transport approaching the quantum conductance limit of
2G 0 = 4e (2)/h has been achieved in field-effect transistors (FETs) containing
one CNT. However, constraints in CNT sorting, processing, alignment, and contacts
give rise to nonidealities when CNTs are implemented in densely packed parallel
arrays such as those needed for technology, resulting in a conductance per CNT
far from 2G 0. The consequence has been that, whereas CNTs are ultimately
expected to yield FETs that are more conductive than conventional semiconductors,
CNTs, instead, have underperformed channel materials, such as Si, by sixfold or
more. We report quasi-ballistic CNT array FETs at a density of 47 CNTs MUm(-1),
fabricated through a combination of CNT purification, solution-based assembly,
and CNT treatment. The conductance is as high as 0.46 G 0 per CNT. In parallel,
the conductance of the arrays reaches 1.7 mS MUm(-1), which is seven times higher
than the previous state-of-the-art CNT array FETs made by other methods. The
saturated on-state current density is as high as 900 MUA MUm(-1) and is similar
to or exceeds that of Si FETs when compared at and equivalent gate oxide
thickness and at the same off-state current density. The on-state current density
exceeds that of GaAs FETs as well. This breakthrough in CNT array performance is
a critical advance toward the exploitation of CNTs in logic, high-speed
communications, and other semiconductor electronics technologies.
PMID- 27617292
TI - A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in
autophagy.
AB - The intronic GGGGCC hexanucleotide repeat expansion in chromosome 9 open reading
frame 72 (C9ORF72) is a prevalent genetic abnormality identified in both
frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Smith
Magenis syndrome chromosomal region candidate gene 8 (SMCR8) is a protein with
unclear functions. We report that C9ORF72 is a component of a multiprotein
complex containing SMCR8, WDR41, and ATG101 (an important regulator of
autophagy). The C9ORF72 complex displays guanosine triphosphatase (GTPase)
activity and acts as a guanosine diphosphate-guanosine 5'-triphosphate (GDP-GTP)
exchange factor (GEF) for RAB39B. We created Smcr8 knockout mice and found that
Smcr8 mutant cells exhibit impaired autophagy induction, which is similarly
observed in C9orf72 knockdown cells. Mechanistically, SMCR8/C9ORF72 interacts
with the key autophagy initiation ULK1 complex and regulates expression and
activity of ULK1. The complex has an additional role in regulating later stages
of autophagy. Whereas autophagic flux is enhanced in C9orf72 knockdown cells,
depletion of Smcr8 results in a reduced flux with an abnormal expression of
lysosomal enzymes. Thus, C9ORF72 and SMCR8 have similar functions in modulating
autophagy induction by regulating ULK1 and play distinct roles in regulating
autophagic flux.
PMID- 27617295
TI - Nanogeochronology of discordant zircon measured by atom probe microscopy of Pb
enriched dislocation loops.
AB - Isotopic discordance is a common feature in zircon that can lead to an erroneous
age determination, and it is attributed to the mobilization and escape of
radiogenic Pb during its post-crystallization geological evolution. The degree of
isotopic discordance measured at analytical scales of ~10 MUm often differs among
adjacent analysis locations, indicating heterogeneous distributions of Pb at
shorter length scales. We use atom probe microscopy to establish the nature of
these sites and the mechanisms by which they form. We show that the nanoscale
distribution of Pb in a ~2.1 billion year old discordant zircon that was
metamorphosed c. 150 million years ago is defined by two distinct Pb reservoirs.
Despite overall Pb loss during peak metamorphic conditions, the atom probe data
indicate that a component of radiogenic Pb was trapped in 10-nm dislocation loops
that formed during the annealing of radiation damage associated with the
metamorphic event. A second Pb component, found outside the dislocation loops,
represents homogeneous accumulation of radiogenic Pb in the zircon matrix after
metamorphism. The (207)Pb/(206)Pb ratios measured from eight dislocation loops
are equivalent within uncertainty and yield an age consistent with the original
crystallization age of the zircon, as determined by laser ablation spot analysis.
Our results provide a specific mechanism for the trapping and retention of
radiogenic Pb during metamorphism and confirm that isotopic discordance in this
zircon is characterized by discrete nanoscale reservoirs of Pb that record
different isotopic compositions and yield age data consistent with distinct
geological events. These data may provide a framework for interpreting
discordance in zircon as the heterogeneous distribution of discrete radiogenic Pb
populations, each yielding geologically meaningful ages.
PMID- 27617296
TI - Salient Segmentation of Medical Time Series Signals.
AB - Searching and mining medical time series databases is extremely challenging due
to large, high entropy, and multidimensional datasets. Traditional time series
databases are populated using segments extracted by a sliding window. The
resulting database index contains an abundance of redundant time series segments
with little to no alignment. This paper presents the idea of "salient
segmentation". Salient segmentation is a probabilistic segmentation technique for
populating medical time series databases. Segments with the lowest probabilities
are considered salient and are inserted into the index. The resulting index has
little redundancy and is composed of aligned segments. This approach reduces
index sizes by more than 98% over conventional sliding window techniques.
Furthermore, salient segmentation can reduce redundancy in motif discovery
algorithms by more than 85%, yielding a more succinct representation of a time
series signal.
PMID- 27617294
TI - Hidden drivers of low-dose pharmaceutical pollutant mixtures revealed by the
novel GSA-QHTS screening method.
AB - The ecological impacts of emerging pollutants such as pharmaceuticals are not
well understood. The lack of experimental approaches for the identification of
pollutant effects in realistic settings (that is, low doses, complex mixtures,
and variable environmental conditions) supports the widespread perception that
these effects are often unpredictable. To address this, we developed a novel
screening method (GSA-QHTS) that couples the computational power of global
sensitivity analysis (GSA) with the experimental efficiency of quantitative high
throughput screening (QHTS). We present a case study where GSA-QHTS allowed for
the identification of the main pharmaceutical pollutants (and their
interactions), driving biological effects of low-dose complex mixtures at the
microbial population level. The QHTS experiments involved the integrated analysis
of nearly 2700 observations from an array of 180 unique low-dose mixtures,
representing the most complex and data-rich experimental mixture effect
assessment of main pharmaceutical pollutants to date. An ecological scaling-up
experiment confirmed that this subset of pollutants also affects typical
freshwater microbial community assemblages. Contrary to our expectations and
challenging established scientific opinion, the bioactivity of the mixtures was
not predicted by the null mixture models, and the main drivers that were
identified by GSA-QHTS were overlooked by the current effect assessment scheme.
Our results suggest that current chemical effect assessment methods overlook a
substantial number of ecologically dangerous chemical pollutants and introduce a
new operational framework for their systematic identification.
PMID- 27617298
TI - Aggregated Indexing of Biomedical Time Series Data.
AB - Remote and wearable medical sensing has the potential to create very large and
high dimensional datasets. Medical time series databases must be able to
efficiently store, index, and mine these datasets to enable medical professionals
to effectively analyze data collected from their patients. Conventional high
dimensional indexing methods are a two stage process. First, a superset of the
true matches is efficiently extracted from the database. Second, supersets are
pruned by comparing each of their objects to the query object and rejecting any
objects falling outside a predetermined radius. This pruning stage heavily
dominates the computational complexity of most conventional search algorithms.
Therefore, indexing algorithms can be significantly improved by reducing the
amount of pruning. This paper presents an online algorithm to aggregate
biomedical times series data to significantly reduce the search space (index
size) without compromising the quality of search results. This algorithm is built
on the observation that biomedical time series signals are composed of cyclical
and often similar patterns. This algorithm takes in a stream of segments and
groups them to highly concentrated collections. Locality Sensitive Hashing (LSH)
is used to reduce the overall complexity of the algorithm, allowing it to run
online. The output of this aggregation is used to populate an index. The proposed
algorithm yields logarithmic growth of the index (with respect to the total
number of objects) while keeping sensitivity and specificity simultaneously above
98%. Both memory and runtime complexities of time series search are improved when
using aggregated indexes. In addition, data mining tasks, such as clustering,
exhibit runtimes that are orders of magnitudes faster when run on aggregated
indexes.
PMID- 27617297
TI - Dynamic Task Optimization in Remote Diabetes Monitoring Systems.
AB - Diabetes is the seventh leading cause of death in the United States, but careful
symptom monitoring can prevent adverse events. A real-time patient monitoring and
feedback system is one of the solutions to help patients with diabetes and their
healthcare professionals monitor health-related measurements and provide dynamic
feedback. However, data-driven methods to dynamically prioritize and generate
tasks are not well investigated in the domain of remote health monitoring. This
paper presents a wireless health project (WANDA) that leverages sensor technology
and wireless communication to monitor the health status of patients with
diabetes. The WANDA dynamic task management function applies data analytics in
real-time to discretize continuous features, applying data clustering and
association rule mining techniques to manage a sliding window size dynamically
and to prioritize required user tasks. The developed algorithm minimizes the
number of daily action items required by patients with diabetes using association
rules that satisfy a minimum support, confidence and conditional probability
thresholds. Each of these tasks maximizes information gain, thereby improving the
overall level of patient adherence and satisfaction. Experimental results from
applying EM-based clustering and Apriori algorithms show that the developed
algorithm can predict further events with higher confidence levels and reduce the
number of user tasks by up to 76.19 %.
PMID- 27617299
TI - An Approach for Incorporating Context in Building Probabilistic Predictive
Models.
AB - With the increasing amount of information collected through clinical practice and
scientific experimentation, a growing challenge is how to utilize available
resources to construct predictive models to facilitate clinical decision making.
Clinicians often have questions related to the treatment and outcome of a medical
problem for individual patients; however, few tools exist that leverage the large
collection of patient data and scientific knowledge to answer these questions.
Without appropriate context, existing data that have been collected for a
specific task may not be suitable for creating new models that answer different
questions. This paper presents an approach that leverages available structured or
unstructured data to build a probabilistic predictive model that assists
physicians with answering clinical questions on individual patients. Various
challenges related to transforming available data to an end-user application are
addressed: problem decomposition, variable selection, context representation,
automated extraction of information from unstructured data sources, model
generation, and development of an intuitive application to query the model and
present the results. We describe our efforts towards building a model that
predicts the risk of vasospasm in aneurysm patients.
PMID- 27617301
TI - Designer Drugs: A Synthetic Catastrophe.
AB - Synthetic stimulants can cause hallucinations, aggressive behaviors, death and
are sometimes legal. These substances are sold as plant food and bath salts that
are "Not for Human Consumption", therefore skirting the 1986 Federal Analogue Act
and giving a false pretense of safety. Studies have proved that these substances
are toxic, have a high abuse potential, and are becoming extremely prevalent in
the United States. This creates a dilemma for law enforcement agents, hospitals,
and substance use disorder treatment centers. Urine Drug Testing is utilized as a
clinical diagnostic tool in substance use disorder treatment centers, and the
furious pace at which new synthetic stimulants are introduced to the black market
are making the detection via urine increasingly difficult. This article will
discuss the prevalence, pharmacology and difficulty developing laboratory assays
to detect synthetic stimulants.
PMID- 27617300
TI - Coupling Neurogenetics (GARSTM) and a Nutrigenomic Based Dopaminergic Agonist to
Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for
Carbohydrate Addiction Algorithms.
AB - Earlier work from our laboratory, showing anti-addiction activity of a
nutraceutical consisting of amino-acid precursors and enkephalinase inhibition
properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor
Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the
development of "Personalized Medicine" in addiction. Prior to the later genetic
finding, we developed the concept of Brain Reward Cascade, which continues to act
as an important component for stratification of addiction risk through
neurogenetics. In 1996 our laboratory also coined the term "Reward Deficiency
Syndrome (RDS)" to define a common genetic rubric for both substance and non
substance related addictive behaviors. Following many reiterations we utilized
polymorphic targets of a number of reward genes (serotonergic, Opioidergic,
GABAergic and Dopaminergic) to customize KB220 [Neuroadaptogen- amino-acid
therapy (NAAT)] by specific algorithms. Identifying 1,000 obese subjects in the
Netherlands a subsequent small subset was administered various KB220Z formulae
customized according to respective DNA polymorphisms individualized that
translated to significant decreases in both Body Mass Index (BMI) and weight in
pounds. Following these experiments, we have been successfully developing a panel
of genes known as "Genetic Addiction Risk Score" (GARSpDX)TM. Selection of 10
genes with appropriate variants, a statistically significant association between
the ASI-Media Version-alcohol and drug severity scores and GARSpDx was found A
variant of KB220Z in abstinent heroin addicts increased resting state functional
connectivity in a putative network including: dorsal anterior cingulate, medial
frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas,
and cerebellum. In addition, we show that KB220Z significantly activates, above
placebo, seed regions of interest including the left nucleus accumbens, cingulate
gyrus, anterior thalamic nuclei, hippocampus, pre-limbic and infra-limbic loci.
KB220Z demonstrates significant functional connectivity, increased brain volume
recruitment and enhanced dopaminergic functionality across the brain reward
circuitry. We propose a Reward Deficiency System Solution that promotes early
identification and stratification of risk alleles by utilizing GARSDx, allowing
for customized nutrigenomic targeting of these risk alleles by altering KB220Z
ingredients as an algorithmic function of carrying these polymorphic DNA-SNPS,
potentially yielding the first ever nutrigenomic solution for addiction and pain.
PMID- 27617303
TI - An Exercise Intervention for South Asian Mothers with Risk Factors for Diabetes.
AB - PURPOSE: South Asians (Indians, Pakistanis, Bangladeshis, Sri Lankans, Nepalis,
and Bhutanese) in the United States have a very high prevalence of type 2
diabetes mellitus (DM). This pilot study evaluated a culturally-tailored exercise
intervention among South Asian immigrant mothers with DM risk factors. METHODS:
Through an academic-community partnership, South Asian women with risk factors
for DM and who had at least one child between 6-14 years were enrolled into this
single-arm study. The intervention for the mothers included 16-weeks of twice
weekly exercise classes, self-monitoring with activity trackers, goal-setting,
and classes on healthy eating. Based on prior community-based participatory
research, children were offered exercise classes during the mothers' classes. The
primary efficacy outcomes were change in mothers' moderate/vigorous physical
activity and body weight pre- and post-intervention (16-weeks). Program
adherence, clinical, and psychosocial outcomes were measured. A qualitative
process evaluation was conducted to understand participant perspectives. RESULTS:
Participants' (n=30) average age was 40 (SD=5) years., 57% had a high school
education or less, and all were overweight/obese.. At baseline, women were not
meeting recommended physical activity guidelines. Overall, participants attended
75% of exercise classes. Compared to baseline, participants' weight decreased by
3.2 lbs. (95% CI: -5.5, -1.0) post-intervention. Among women who attended at
least 80% of classes (n=17), weight change was -4.8 lbs, (95% CI: -7.7, -1.9).
Change in accelerometer-measured physical activity was not significant; however
exercise-related confidence increased from baseline (p-value <0.01). Women
described multiple physical and psychosocial benefits from the intervention.
CONCLUSION: This pilot study suggests that a culturally-tailored exercise
intervention that included exercise classes for children was feasible and had
physical and psychosocial benefits in South Asian mothers with risk factors for
DM.
PMID- 27617304
TI - Epigenetic remodeling regulates transcriptional changes between ovarian cancer
and benign precursors.
AB - Regulation of lineage-restricted transcription factors has been shown to
influence malignant transformation in several types of cancer. Whether similar
mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a
nuclear transcription factor that controls the embryologic development of the
Mullerian system, including the fallopian tubes. Recent studies have shown that
fallopian tube secretory epithelial cells (FTSECs) give rise to the most common
form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs). We
designed the present study in order to understand whether changes in gene
expression between FTSECs and HGSOCs relate to alterations in PAX8 binding to
chromatin. Using whole transcriptome shotgun sequencing (RNA-Seq) after PAX8
knockdown and ChIP-Seq, we show that FTSECs and HGSOCs are distinguished by
marked reprogramming of the PAX8 cistrome. Genes that are significantly altered
between FTSECs and HGSOCs are enriched near PAX8 binding sites. These sites are
also near TEAD binding sites, and these transcriptional changes may be related to
PAX8 interactions with the TEAD/YAP1 signaling pathway. These data suggest that
transcriptional changes after transformation in ovarian cancer are closely
related to epigenetic remodeling in lineage-specific transcription factors.
PMID- 27617302
TI - Brain Reward Pathway Dysfunction in Maternal Depression and Addiction: A Present
and Future Transgenerational Risk.
AB - Two research areas that could benefit from a greater focus on the role of the
reward pathway are maternal depression and maternal addiction. Both depression
and addiction in mothers are mediated by deficiencies in the reward pathway and
represent substantial risks to the health of offspring and future generations.
This targeted review discusses maternal reward deficits in depressed and addicted
mothers, neural, genetic, and epigenetic mechanisms, and the transgenerational
transmission of these deficits from mother to offspring. Postpartum depression
and drug use disorders may entail alterations in the reward pathway, particularly
in striatal and prefrontal areas, which may affect maternal attachment to
offspring and heighten the risk of transgenerational effects on the oxytocin and
dopamine systems. Alterations may involve neural circuitry changes, genetic
factors that impact monoaminergic neurotransmission, as well as growth factors
such as BDNF and stress-associated signaling in the brain. Improved maternal
reward-based preventative measures and treatments may be specifically effective
for mothers and their offspring suffering from depression and/or addiction.
PMID- 27617305
TI - The mitogenome of the bed bug Cimex lectularius (Hemiptera: Cimicidae).
AB - We report the extraction of a bed bug mitogenome from high-throughput sequencing
projects originally focused on the nuclear genome of Cimex lectularius. The
assembled mitogenome has a similar AT nucleotide composition bias found in other
insects. Phylogenetic analysis of all protein-coding genes indicates that C.
lectularius is clearly a member of a paraphyletic Cimicomorpha clade within the
Order Hemiptera.
PMID- 27617306
TI - Effective physiology teaching methods: from the perspective of first year MBBS
students.
AB - BACKGROUND: Students who took admission in first year MBBS course used to study
physiology, anatomy and biochemistry for one and half years. Since a decade the
first year course duration was reduced to one year unaltering the syllabus in the
three basic subjects. So students are focusing on the easy ways to clear the
university exams by accepting the concise books, which is dampening the real
quality of the subject knowledge. This study is aimed at understanding the best
methods of physiology teaching in the lecture gallery, from the student's
perspective. MATERIALS AND METHODS: The present study was undertaken at a private
medical college in southern part of India in Telangana state, on 100 students who
took admission in first year MBBS course, in the academic year 2015-2016. Out of
100, 36 are boys and 64 are girl students. Distributed a question paper which is
having 2 sets of questions. First question is having three statements regarding
the teaching methods namely; chalk and blackboard teaching, over head projection
teaching and power point teaching. Students were asked to choose the best
statement which they prefer. Second question is consisting of combination of
teaching methods and they are; chalk and blackboard with over head projection
teaching method, chalk and blackboard with power point presentation. Again the
students were asked to choose one of the 2 statements in 2nd question. RESULTS:
Students preference of teaching methods for understanding of physiology in
percentage; chalk and blackboard-54, over head projection teaching-4, power point
presentation-32, chalk and blackboard with over head projection-26, chalk and
blackboard with power point presentation-64. CONCLUSION: Majority of the students
are in favor of a combination of chalk and blackboard with power point
presentation for better understanding of physiology, next is chalk and blackboard
teaching alone.
PMID- 27617308
TI - Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer.
AB - Adipocytes promote progression of multiple cancers, but their role in pancreatic
intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly
defined. Nutrient transfer is a mechanism underlying stromal cell-cancer
crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and
PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1
adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were
used to model PanIN and PDAC. Co-culture was used to study the effect of
adipocytes on PanIN and PDAC cell proliferation in response to manipulation of
glutamine metabolism. Glutamine secretion was measured with a bioanalyzer.
Western blotting was used to study the effect of PanIN and PDAC cells on
expression of glutamine-related enzymes in adipocytes. Adipocytes promote
proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient
poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell
proliferation in the absence of glutamine, an effect that was glutamine
synthetase-dependent and involved PDAC cell-induced down-regulation of
glutaminase expression in adipocytes. These findings suggest glutamine transfer
as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell
proliferation.
PMID- 27617307
TI - PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is
Associated with Worse Recurrence-free Survival in Prostate Cancer.
AB - BACKGROUND: PTEN is the most commonly deleted tumor suppressor gene in primary
prostate cancer (PCa) and its loss is associated with poor clinical outcomes and
ERG gene rearrangement. OBJECTIVE: We tested whether PTEN loss is associated with
shorter recurrence-free survival (RFS) in surgically treated PCa patients with
known ERG status. DESIGN SETTING AND PARTICIPANTS: A genetically validated,
automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary
prostate tumors from the Canary Foundation retrospective PCa tissue microarray
cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a
subset of tumor tissue sampled) PTEN loss. ERG status as determined by a
genetically validated IHC assay was available for a subset of 938 tumors. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between PTEN and ERG status
were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted
Cox proportional models for RFS were constructed. RESULTS AND LIMITATIONS: When
compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not
heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with
shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR
3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was
significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did
not reach significance for inclusion in the final multivariate models. The
interaction term for PTEN and ERG status with respect to RFS did not reach
statistical significance (p = 0.11) for the current sample size. CONCLUSIONS:
These data suggest that PTEN is a useful prognostic biomarker and that there is
no statistically significant interaction between PTEN and ERG status for RFS.
PATIENT SUMMARY: We found that loss of the PTEN tumor suppressor gene in prostate
tumors as assessed by tissue staining is correlated with shorter time to prostate
cancer recurrence after radical prostatectomy.
PMID- 27617309
TI - Human papillomaviruses: research priorities for the next decade.
AB - Human papillomaviruses are the causative agents of cervical, anal as well as many
oropharyngeal cancers. While prophylactic vaccines have been developed, uptake is
low in the US and other Western countries, and access is limited in less
developed countries. A number of areas are emerging as critical for future study.
These include investigation of the mechanisms regulating infection and
progression to cancer at both cervical and oropharyngeal sites as these appear to
be distinct. HPV-induced cancers also may be susceptible to immune therapy,
revealing opportunities for treating advanced cervical disease and reducing the
morbidity of treatments for oropharyngeal cancers. We believe these areas are
critical focal points for HPV cancer research in the next decade.
PMID- 27617310
TI - Liquid biopsy? A recent breakthrough in noninvasive bladder cancer surveillance.
PMID- 27617311
TI - Urethral strictures after radiation therapy for prostate cancer.
AB - Urethral stricture after radiation therapy for localized prostate cancer is a
delicate problem as the decreased availability of tissue healing and the close
relation to the sphincter complicates any surgical approach. We here review the
pathophysiology, dosimetry, and the disease specific aspects of urethral
strictures after radiotherapy. Moreover we discuss different treatment option
such as direct vision internal urethrotomy as well as techniques for open
reconstruction with and without tissue transfer.
PMID- 27617312
TI - Augmentation cystoplasty in neurogenic bladder.
AB - The aim of this review is to update the indications, contraindications,
technique, complications, and the tissue engineering approaches of augmentation
cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched
for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder
augmentation." Additional relevant literature was determined by examining the
reference lists of articles identified through the search. The update review of
of the indications, contraindications, technique, outcome, complications, and
tissue engineering approaches of AC in patients with neurogenic bladder is
presented. Although some important progress has been made in tissue engineering
AC, conventional AC still has an important role in the surgical treatment of
refractory neurogenic lower urinary tract dysfunction.
PMID- 27617313
TI - Clinical significance of preoperative thrombocytosis in patients who underwent
radical nephrectomy for nonmetastatic renal cell carcinoma.
AB - PURPOSE: The aim of this study was to examine the association of preoperative
thrombocytosis with the prognosis of patients with nonmetastatic renal cell
carcinoma (RCC). MATERIALS AND METHODS: We conducted a retrospective analysis of
187 patients who underwent a radical nephrectomy for nonmetastatic RCC between
July 1997 and June 2009. Thrombocytosis was defined as a platelet count>=400,000
uL, and patients were divided into 2 groups according to presence of preoperative
thrombocytosis, and the cancer-specific survival rates and overall survival rates
of the 2 groups after radical nephrectomy were compared. RESULTS: The mean age of
the patients was 56.0+/-11.7 years and the mean follow-up period was 59.3+/-42.1
months; there were 20 patients with preoperative thrombocytosis. Thirty patients
developed metastases and 9 patients died during the follow-up period. In Kaplan
Meier analysis using a univariate log-rank test, both cancer-specific survival
rate (p=0.013) and overall survival rate (p=0.012) showed significant association
with preoperative thrombocytosis. Controlling for pathological TNM stage, Fuhrman
grade and tumor diameter, the Cox proportional hazards model for cancer-specific
survival rates showed that preoperative thrombocytosis was an independent
prognostic factor (p=0.025). CONCLUSIONS: Preoperative thrombocytosis was
associated with poorer prognosis in patients with nonmetastatic RCC. Thus,
preoperative platelet count may be clinically useful for risk stratification of
patients undergoing surgery for nonmetastatic RCC.
PMID- 27617314
TI - Second primary cancers in patients with urothelial cancers.
AB - PURPOSE: To investigate the second primary cancers (SPCs) in patients with
urothelial cancer (UC). MATERIALS AND METHODS: The records of 2,339 patients
whose UC was diagnosed between January 1974 and December 2012 were reviewed. All
data about characteristics of patients, of UC and, of SPC was, recorded
digitally. We investigated the prevalence and the type of second or higher order
cancers, and the factors associated with SPC. RESULTS: Total 260 patients (11.1%)
had SPC, 14 had a third primary cancer and one had a fourth primary cancer. The
most common SPC with UC was lung cancer (29.6%). Of all 260 with SPC, 64 (24.6%)
had synchronous (within the 6 months) SPC, 120 (46.2%) had subsequent SPC and, 76
(29.2%) had antecedent SPC. The mean duration of SPC was 56 months in patients
with subsequent SPC and 75.8 months in patients with antecedent SPC. The mean age
at the time of diagnosis of UC was higher in patients with SPC. The ratio of male
gender, body mass index, blood type, status of smoking and, occupational risk was
similar in both groups. Total amount of smoking and the mean follow-up were
higher in patients with SPC. CONCLUSIONS: The majority of the patients with UC
have long life expectancy. In patients with UC, the risk of having another cancer
is quite higher than normal population. The physicians managing patients with UC
should look for SPC.
PMID- 27617315
TI - Extended use of Prostate Health Index and percentage of [-2]pro-prostate-specific
antigen in Chinese men with prostate specific antigen 10-20 ng/mL and normal
digital rectal examination.
AB - PURPOSE: We investigated the extended use of Prostate Health Index (PHI) and
percentage of [-2]pro-prostate-specific antigen (%p2PSA) in Chinese men with
prostate-specific antigen (PSA) 10-20 ng/mL and normal digital rectal examination
(DRE). MATERIALS AND METHODS: All consecutive Chinese men with PSA 10-20 ng/mL
and normal DRE who agreed for transrectal ultrasound (TRUS)-guided 10-core
prostate biopsy were recruited. Blood samples were taken immediately before TRUS
guided prostate biopsy. The performances of total PSA (tPSA), %free-to-total PSA
(%fPSA), %p2PSA, and PHI were compared using logistic regression, receiver
operating characteristic, and decision curve analyses (DCA). RESULTS: From 2008
to 2015, 312 consecutive Chinese men were included. Among them, 53 out of 312
(17.0%) men were diagnosed to have prostate cancer on biopsy. The proportions of
men with positive biopsies were 6.7% in PHI<35, 22.8% in PHI 35-55, and 54.5% in
PHI>55 (chi-square test, p<0.001). The area under curves (AUC) of the base model
including age, tPSA and status of initial/repeated biopsy was 0.64. Adding %p2PSA
and PHI to the base model improved the AUC to 0.79 (p<0.001) and 0.78 (p<0.001),
respectively, and provided net clinical benefit in DCA. The positive biopsy rates
of Gleason 7 or above prostate cancers were 2.2% for PHI<35, 7.9% for PHI 35-55,
and 36.4% for PHI>55 (chi-square test, p<0.001). By utilizing the PHI cutoff of
35 to men with PSA 10-20 ng/mL and normal DRE, 57.1% (178 of 312) biopsies could
be avoided. CONCLUSIONS: Both PHI and %p2PSA performed well in predicting
prostate cancer and high grade prostate cancer. The use of PHI and %p2PSA should
be extended to Chinese men with PSA 10-20 ng/mL and normal DRE.
PMID- 27617316
TI - Clinical factors associated with postoperative hydronephrosis after ureteroscopic
lithotripsy.
AB - PURPOSE: This study aimed to determine the predictors of ipsilateral
hydronephrosis after ureteroscopic lithotripsy for ureteral calculi. MATERIALS
AND METHODS: From January 2010 to December 2014, a total of 204 patients with
ureteral calculi who underwent ureteroscopic lithotripsy were reviewed. Patients
with lack of clinical data, presence of ureteral rupture, and who underwent
simultaneous percutaneous nephrolithotomy (PNL) were excluded. Postoperative
hydronephrosis was determined via computed tomographic scan or renal
ultrasonography, at 6 months after ureteroscopic lithotripsy. Multivariable
analysis was performed to determine clinical factors associated with ipsilateral
hydronephrosis. RESULTS: A total of 137 patients were enrolled in this study. The
mean age of the patients was 58.8+/-14.2 years and the mean stone size was 10.0+/
4.6 mm. The stone-free rate was 85.4%. Overall, 44 of the 137 patients (32.1%)
had postoperative hydronephrosis. Significant differences between the
hydronephrosis and nonhydronephrosis groups were noted in terms of stone
location, preoperative hydronephrosis, impacted stone, operation time, and
ureteral stent duration (all, p<0.05). On multivariable analysis, increasing
preoperative diameter of the hydronephrotic kidney (adjusted odds ratio [OR],
1.21; 95% confidence interval [CI], 1.12-1.31; p=0.001) and impacted stone
(adjusted OR, 3.01; 95% CI, 1.15-7.61; p=0.031) independently predicted the
occurrence of postoperative hydronpehrosis. CONCLUSIONS: Large preoperative
diameter of the hydronephrotic kidney and presence of impacted stones were
associated with hydronephrosis after ureteroscopic stone removal. Therefore,
patients with these predictive factors undergo more intensive imaging follow-up
in order to prevent renal deterioration due to postoperative hydronephrosis.
PMID- 27617317
TI - Tamsulosin versus tadalafil as a medical expulsive therapy for distal ureteral
stones: A prospective randomized study.
AB - PURPOSE: This study aimed to compare the safety and efficacy of tamsulosin and
tadalafil as medical expulsive therapy for distal ureteral stones. MATERIALS AND
METHODS: This prospective randomized study was conducted at the Department of
Urology of Bir Hospital over a period of 12 months in patients with distal
ureteral stones sized 5 to 10 mm. Patients were randomly divided into 2 groups:
group A received tamsulosin 0.4 mg and group B received tadalafil 10 mg at
bedtime for 2 weeks. Stone expulsion rate, number of ureteric colic episodes and
pain score, analgesic requirements, and adverse drug effects were noted in both
groups. Statistical analyses were performed by using Student t-test and chi
square test. RESULTS: Altogether 85 patients, 41 in group A and 44 in group B,
were enrolled in the study. The patients' average age was 31.72+/-12.63 years,
and the male-to-female ratio was 1.5:1. Demographic profiles, stone size, and
baseline investigations were comparable between the 2 groups. The stone expulsion
rate was significantly higher in the tadalafil group than in the tamsulosin group
(84.1% vs. 61.0%, p=0.017). Although the occurrence of side effects was higher
with tadalafil, this difference was not significant (p=0.099). There were no
serious adverse effects. CONCLUSIONS: Tadalafil has a significantly higher stone
expulsion rate than tamsulosin when used as a medical expulsive therapy for
distal ureteral stones sized 5-10 mm. Both drugs are safe, effective, and well
tolerated with minor side effects.
PMID- 27617319
TI - Preperitoneal placement of an inflatable penile prosthesis reservoir for
postoperative erectile dysfunction after radical cystoprostatectomy with
orthotopic neobladder.
AB - PURPOSE: To describe a case of safe placement of an inflatable penile prosthesis
reservoir for postoperative erectile dysfunction (ED) with a history of radical
cystoprostatectomy with an orthotopic Studer neobladder. MATERIALS AND METHODS: A
55-year-old bladder cancer patient, who underwent radical cystoprostatectomy with
orthotopic Studer neobladder 2 years prior, suffered from postoperative ED. A 3
piece inflatable penile prosthesis was implanted via a penoscrotal incision. The
alternative reservoir placement began with a longitudinal 4-cm incision, which
was 2 finger-breaths to the left and lateral to the umbilicus. Thereafter, the
anterior and posterior rectus sheaths were dissected and incised. Then, the
transversalis fascia entering into the preperitoneal space was incised, followed
by circumferential sweeping using the forefinger, and, finally, placement of a
100 mL 'flat' reservoir. The reservoir was filled with 65 mL saline and then
evaluated for back pressure. The reservoir tubing exited through the defect of
the rectus sheaths and tunneled through the abdominal fat into the penoscrotal
wound. RESULTS: Total operative time was 105 minutes, and the estimated blood
loss was minimal. The patient was discharged at postoperative day 1 and
experienced no perioperative complications. At the 6-month follow-up, there was
no abdominal bulging from the preperitoneal reservoir, and the reservoir was not
palpable. CONCLUSIONS: The preperitoneal placement of the flat reservoir at the
level of the umbilicus is a safe and acceptable surgical technique for
postoperative ED after radical cystoprostatectomy with orthotopic neobladder.
PMID- 27617318
TI - Phosphodiesterase type 5 inhibitor administered immediately after radical
prostatectomy temporarily increases the need for incontinence pads, but improves
final continence status.
AB - PURPOSE: To evaluate the effects of phosphodiesterase type 5 inhibitor (PDE5i) on
urinary continence recovery after bilateral nerve-sparing radical prostatectomy
(BNSRP). MATERIALS AND METHODS: Between 2002 and 2012, 137 of 154 consecutive
patients who underwent BNSRP in our institution retrospectively divided into 3
groups that included patients taking PDE5i immediately after surgery (immediate
PDE5i group, n=41), patients starting PDE5i at an outpatient clinic after
discharge (PDE5i group, n=56), and patients taking no medication (non-PDE5i
group, n=40). Using self-administered questionnaires, the proportion of patients
who did not require incontinence pads (pad-free patients) was calculated
preoperatively and at 1, 3, 6, 12, 18, and 24 months after BNSRP. Severity of
incontinence was determined based on the pad numbers and then compared among the
3 groups. RESULTS: Proportions of pad-free patients and severity of incontinence
initially deteriorated in all of the groups to the lowest values soon after
undergoing BNSRP, with gradual improvement noted thereafter. The deterioration
was most prominent in the immediate PDE5i group. As compared to the non-PDE5i
group, both the PDE5i and immediate PDE5i groups exhibited a better final
continence status. CONCLUSIONS: PDE5i improves final continence status. However,
administration of PDE5i immediately after surgery causes a distinct temporary
deterioration in urinary incontinence.
PMID- 27617321
TI - Corrigendum: Correction of the unit for stone size in the ABSTRACT and RESULTS
section. The Gachon University Ureteral Narrowing score: A comprehensive
standardized system for predicting necessity of ureteral dilatation to treat
proximal ureteral calculi.
AB - [This corrects the article on p. 280 in vol. 57.].
PMID- 27617320
TI - An unusual cause of urinary incontinence: Urethral coitus in a case of Mayer
Rokitansky-Kuster-Hauser syndrome.
AB - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare anomaly in women and is
characterized by congenital aplasia of the uterus and vagina, with normal
development of secondary sexual characteristics and a normal karyotype. We report
a case of a 38-year-old women with MRKH syndrome that had experienced urethral
sex for many years. She presented with urinary incontinence and dyspareunia. The
patient's secondary sexual characteristics were normal, and examination revealed
a widely open incompetent megalourethra and an absent vagina. Laboratory studies
confirmed a 46, XX karyotype. Imaging included ultrasonography and magnetic
resonance imaging, which indicated bilateral normal ovaries and a rudimental
bicornuate uterus. After confirming the diagnosis of MRKH, the patient underwent
urethroplasty by urethral plication, antiincontinence surgery by autologous
fascial sling of the bladder neck, and the creation of a neo-vagina using a
urethral flap. After 3 months, voiding cystourethrography and uroflowmetry
confirmed normal voiding. There were no postoperative symptoms of urinary
incontinence, and the patient was completely satisfied.
PMID- 27617322
TI - Corrigendum: Correction of title spelling. Progressive changes in detrusor
function and micturition patterns with chronic bladder ischemia.
AB - [This corrects the article on p. 249 in vol. 57.].
PMID- 27617323
TI - Photoluminescence Blinking of Single-Crystal Methylammonium Lead Iodide
Perovskite Nanorods Induced by Surface Traps.
AB - Photoluminescence (PL) of organometal halide perovskite materials reflects the
charge dynamics inside of the material and thus contains important information
for understanding the electro-optical properties of the material. Interpretation
of PL blinking of methylammonium lead iodide (MAPbI3) nanostructures observed on
polycrystalline samples remains puzzling owing to their intrinsic disordered
nature. Here, we report a novel method for the synthesis of high-quality single
crystal MAPbI3 nanorods and demonstrate a single-crystal study on MAPbI3 PL
blinking. At low excitation power densities, two-state blinking was found on
individual nanorods with dimensions of several hundred nanometers. A super
resolution localization study on the blinking of individual nanorods showed that
single crystals of several hundred nanometers emit and blink as a whole, without
showing changes in the localization center over the crystal. Moreover, both the
blinking ON and OFF times showed power-law distributions, indicating trapping
detrapping processes. This is further supported by the PL decay times of the
individual nanorods, which were found to correlate with the ON/OFF states.
Furthermore, a strong environmental dependence of the nanorod PL blinking was
revealed by comparing the measurements in vacuum, nitrogen, and air, implying
that traps locate close to crystal surfaces. We explain our observations by
proposing surface charge traps that are likely related to under-coordinated lead
ions and methylammonium vacancies to result in the PL blinking observed here.
PMID- 27617324
TI - The Early Use of Blinding in Therapeutic Clinical Research of Neurological
Disorders.
AB - We sought to identify early uses of blinding in therapeutic clinical trials of
neurological disorders by multiple search methods. A 1784 report by Benjamin
Franklin and others described the evaluation of the use of Mesmerism to treat
neurological and other syndromes including headache and epilepsy, using
blindfolds and screens. This report demonstrated the usefulness of blinding to
reduce bias in clinical research, yet despite this early discovery, blinding was
not widely accepted or routinely used until the 20th century. Blinded clinical
trials began to be used for various neurological syndromes in the 1950s,
sporadically at first and then increasing in frequency in subsequent years. The
reason for this delay is unclear, but we propose several hypotheses.
PMID- 27617325
TI - Demonstration of Hadoop-GIS: A Spatial Data Warehousing System Over MapReduce.
AB - The proliferation of GPS-enabled devices, and the rapid improvement of scientific
instruments have resulted in massive amounts of spatial data in the last decade.
Support of high performance spatial queries on large volumes data has become
increasingly important in numerous fields, which requires a scalable and
efficient spatial data warehousing solution as existing approaches exhibit
scalability limitations and efficiency bottlenecks for large scale spatial
applications. In this demonstration, we present Hadoop-GIS - a scalable and high
performance spatial query system over MapReduce. Hadoop-GIS provides an efficient
spatial query engine to process spatial queries, data and space based
partitioning, and query pipelines that parallelize queries implicitly on
MapReduce. Hadoop-GIS also provides an expressive, SQL-like spatial query
language for workload specification. We will demonstrate how spatial queries are
expressed in spatially extended SQL queries, and submitted through a command
line/web interface for execution. Parallel to our system demonstration, we
explain the system architecture and details on how queries are translated to
MapReduce operators, optimized, and executed on Hadoop. In addition, we will
showcase how the system can be used to support two representative real world use
cases: large scale pathology analytical imaging, and geo-spatial data
warehousing.
PMID- 27617326
TI - Recruitment of Family Child Care Homes for an Obesity Prevention Intervention
Study.
AB - OBJECTIVE: Critical to the success of any intervention study is successful
recruitment. The aim of this paper was to examine the recruitment process of a
randomized controlled trial evaluating an intervention conducted with family
child care home providers. Specifically, the recruitment challenges, the efforts
employed to address the challenges, and their impact on participant recruitment
are discussed. METHODS: The study's original recruitment protocol was employed
during waves 1 and 2 (out of 5). However, recruitment tracking showed a failure
to meet enrollment targets, particularly in wave 2. Low enrollment prompted an
all-day retreat to discuss potential revisions and enhancements to recruitment
strategies. Four strategies to enhance the recruitment protocol emerged from the
retreat: improving recruitment materials to enhance communication, increasing
engagement with community partners, addressing provider concerns about
participation and study burden, and facilitating parent engagement. RESULTS: The
study successfully recruited 166 family child care home providers across the 5
waves. There was a significant impact on the recruitment of waves 3-5 versus
waves 1-2 using the enhanced recruitment protocol. There was a dramatic increase
in those who "consented" (43% vs. 60%, respectively) and a corresponding decrease
in the percent of "interested and eligible" who then "failed to consent" (57% vs.
40%, respectively). CONCLUSION: Results of these enhanced recruitment strategies
demonstrate the many lessons learned about successful recruitment of a difficult
to-reach population, family child care homes; specifically, the importance of
building relationships, communicating clearly, and identifying key motivators.
PMID- 27617327
TI - 18F-FDG-PET/CT in unexplained elevated inflammatory markers. Joining entities.
AB - : The diagnostic strategy in patients with fever or inflammation of unknown
origin remains a major clinical challenge. The aim of this study was to evaluate
the role of 18F-FDG-PET/CT in patients with unexplained elevated C-reactive
protein with or without fever. Contribution of 18F-FDG-PET/CT to the final
diagnosis was evaluated. In addition we determined whether a differentiation
between patients with or without fever is clinically reasonable. PATIENTS,
METHODS: We retrospectively analysed 72 consecutive patients with unexplained
elevated C-reactive protein levels (above 8mg/l) that underwent 18F-FDG-PET/CT in
our facility between 10/2009 and 11/2012. 18F-FDG-PET/CT was considered a so
called diagnostic scan when results decisively led to a final diagnosis and
adequate therapy with a response of symptoms was initiated due to the PET/CT
result. RESULTS: In 60/72 patients (83%) a final diagnosis was established.
Diagnoses included infections (58%), non-infectious inflammatory diseases (29%)
and malignancies (8%). 18F-FDG-PET/CT was true positive in 47 cases (65%) and the
diagnostic scan in 29 patients (40%). Sensitivity of 18F-FDG-PET/CT was 81% and
specificity was 86%. Diagnostics, final diagnoses, 18F-FDG-PET/CT results,
SUVmax, C-reactive protein levels and the diagnostic scan did not differ
significantly between patients with fever and patients without fever. CONCLUSION:
18F-FDG-PET/CT is a useful method in the diagnostic workup of patients with
inflammation of unknown origin. In our series there was no significant difference
between patients with or without fever. Regarding 18F-FDG-PET/CT-imaging
inflammation of unknown origin and unexplained fever can be joined to one entity.
PMID- 27617328
TI - Usefulness of Health Registers for detection of bleeding events in outcome
studies.
AB - Administrative and claims databases are attractive for safety studies of
anticoagulant and antithrombotic drugs. However, the validity of such data is
often uncertain. It was our aim to assess the usefulness of the Swedish
administrative health databases for detection of major bleeding events. All
individuals with atrial fibrillation in Stockholm County from 2006 to 2013
(n=78,022) were identified from the Swedish Patient register. A search for
bleeding diagnoses was done in the Patient register and in the Cause of Death
register. The medical records of a random sample of 761 patients were studied and
classified in a blinded and pre-specified way. The highest sensitivity (99.5 %)
and specificity (94.0 %) were obtained by counting fatal bleeding events with the
bleeding diagnosis recorded as first or second cause of death, and all
hospitalisations without regard to the position of the diagnosis. Codes for
transfusions were unreliable and did not increase accuracy. The registries
identified 99.4 % of intracranial bleeding events and 82.6 % of gastrointestinal
bleeding events correctly. All patients classified as "no bleedings" were indeed
without bleeding. Overall the sensitivity was 85.5 % and the specificity 95.9 %
for major bleeding events. In conclusion, Swedish nationwide health registries
are well suited for conducting outcome studies involving identification of
bleeding events. The use of a diagnostic code for bleeding, irrespective of its
position as primary or secondary diagnosis, provided the best sensitivity and
specificity for detection of bleeding events, as long as it was limited to
contacts resulting in hospital admission.
PMID- 27617329
TI - Non-Point Source Pollutant Load Variation in Rapid Urbanization Areas by Remote
Sensing, Gis and the L-THIA Model: A Case in Bao'an District, Shenzhen, China.
AB - Urban sprawl is a major driving force that alters local and regional hydrology
and increases non-point source pollution. Using the Bao'an District in Shenzhen,
China, a typical rapid urbanization area, as the study area and land-use change
maps from 1988 to 2014 that were obtained by remote sensing, the contributions of
different land-use types to NPS pollutant production were assessed with a
localized long-term hydrologic impact assessment (L-THIA) model. The results show
that the non-point source pollution load changed significantly both in terms of
magnitude and spatial distribution. The loads of chemical oxygen demand, total
suspended substances, total nitrogen and total phosphorus were affected by the
interactions between event mean concentration and the magnitude of changes in
land-use acreages and the spatial distribution. From 1988 to 2014, the loads of
chemical oxygen demand, suspended substances and total phosphorus showed clearly
increasing trends with rates of 132.48 %, 32.52 % and 38.76 %, respectively,
while the load of total nitrogen decreased by 71.52 %. The immigrant population
ratio was selected as an indicator to represent the level of rapid urbanization
and industrialization in the study area, and a comparison analysis of the
indicator with the four non-point source loads demonstrated that the chemical
oxygen demand, total phosphorus and total nitrogen loads are linearly related to
the immigrant population ratio. The results provide useful information for
environmental improvement and city management in the study area.
PMID- 27617330
TI - Mapping Water Vulnerability of the Yangtze River Basin: 1994-2013.
AB - A holistic understanding of the magnitude and long-term trend of water
vulnerability is essential for making management decisions in a given river
basin. Existing procedures to assess the spatiotemporal dynamic of water
vulnerability in complex mega-scale river basins are inadequate; a new method
named ensemble hydrologic assessment was proposed in this study, which allows
collection of data and knowledge about many aspects of water resources to be
synthesized in a useful way for vulnerability assessment. The objective of this
study is to illustrate the practical utility of such an integrated approach in
examining water vulnerability in the Yangtze River Basin. Overall, the results
demonstrated that the ensemble hydrologic assessment model could largely explain
the spatiotemporal evolution of water vulnerability. This paper improves
understanding of the status and trends of water resources in the Yangtze River
Basin.
PMID- 27617331
TI - Colorimetric Fluorescent Sensors for Hemoglobin Based on BODIPY Dyes.
AB - Colorimetric fluorescent chemosensors 4 and 5 based on mono- and di- styryl
borondipyrromethenes (BODIPY) linked methyl malonyl were designed for detection
of hemoglobin (HgB). Their sensing behavior toward various analytes (Br-, EDTA,
Glucose, CO32-, Fe2+, Fe3+, I-, NO3-, PO43-, SO42-,Cl-, Urea, K+, Mg2+, Na+,
NH4+, Zn2+,Ca2+,Cd2+, Li+, Pb2+, Cs2+, Ag+, Mn2+, Cr2+, Ni2+, Hg2+, Al3+) were
investigated by fluorescence spectroscopies. Addition of HgB to acetone: water
(4:1) solutions of BODIPYs 4 and 5 solutions gave visual color changes, as well
as significantly quenched fluorescence emissions, while other analytes induced no
or much smaller spectral changes. The sensing method for both BODIPYs 4 and 5 was
successfully applied to measure the HgB in human blood with satisfactory results.
Spike and recovery tests in human blood samples exhibit good recovery rates for
the spiked concentrations close to the limit of detection. It was found that
BODIPYs 4 and 5 constituted the HgB selective fluorescent chemosensor (ON-OFF)
and the detection limits were calculated to be 1.773 MUg. mL-1 and 1. 295 MUg.mL
1 respectively.
PMID- 27617332
TI - Alcohol Use and HIV Prevention Among Personnel in the Belize Defence Force.
AB - To evaluate the effect of a peer-based risk reduction project on alcohol use and
sexual behavior within Belize Defence Force personnel. We used a quasi
experimental, mixed quantitative and qualitative methods design to evaluate
project outcomes. Two serial cross-sectional surveys were conducted [baseline (n
= 126) and 6-month follow-up (n = 128)] using computer assisted self-interview.
Semistructured interviews were collected from 12 peer counselors 3 months after
the beginning of the project. The proportion of respondents screening positive
for alcohol dependence decreased significantly from 80 % at preintervention to 66
% at postintervention (p = 0.045), and the percentage of respondents reporting
that they normally drink alcohol before work decreased from 11 to 3 % (p =
0.013). Alcohol abuse and dependency scores correlated positively with the
overall number of sexual partners in both male and female respondents. There was
a slight decrease in the percentage of female respondents' reporting inconsistent
condom use for vaginal sex (baseline 100 %, follow-up 83 %, p = 0.088), but there
was no appreciable change reported in condom use among male respondents.
Qualitative findings suggest that techniques to reduce the quantity of alcohol
consumed were a salient focus of peer counselors, and administrative barriers can
readily mitigate implementation of such interventions. In this evaluation of a
risk reduction program with the BDF, we found evidence of a reduction in types of
alcohol use from baseline to follow-up. Alcohol-related risk reductions carry
implications for reducing sexual risk behavior in military personnel. Future
research with stronger experimental design strategies may better elucidate how
substance use reduction is linked with sexual risk reduction in military
personnel.
PMID- 27617333
TI - Persistent organochlorine pesticides and polychlorinated biphenyls in air of the
North Sea region and air-sea exchange.
AB - Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were
studied to determine occurrence, levels and spatial distribution in the marine
atmosphere and surface seawater during cruises in the German Bight and the wider
North Sea in spring and summer 2009-2010. In general, the concentrations found in
air are similar to, or below, the levels at coastal or near-coastal sites in
Europe. Hexachlorobenzene and alpha-hexachlorocyclohexane (alpha-HCH) were close
to phase equilibrium, whereas net atmospheric deposition was observed for gamma
HCH. The results suggest that declining trends of HCH in seawater have been
continuing for gamma-HCH but have somewhat levelled off for alpha-HCH. Dieldrin
displayed a close to phase equilibrium in nearly all the sampling sites, except
in the central southwestern part of the North Sea. Here atmospheric deposition
dominates the air-sea exchange. This region, close to the English coast, showed
remarkably increased surface seawater concentrations. This observation depended
neither on riverine input nor on the elevated abundances of dieldrin in the air
masses of central England. A net depositional flux of p,p'-DDE into the North Sea
was indicated by both its abundance in the marine atmosphere and the changes in
metabolite pattern observed in the surface water from the coast towards the open
sea. The long-term trends show that the atmospheric concentrations of DDT and its
metabolites are not declining. Riverine input is a major source of PCBs in the
German Bight and the wider North Sea. Atmospheric deposition of the lower
molecular weight PCBs (PCB28 and PCB52) was indicated as a major source for
surface seawater pollution.
PMID- 27617334
TI - Effects of pharmaceuticals and personal care products on marine organisms: from
single-species studies to an ecosystem-based approach.
AB - Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging
concern that are increasing in use and have demonstrated negative effects on
aquatic organisms. There is a growing body of literature reporting the effects of
PPCPs on freshwater organisms, but studies on the effects of PPCPs to marine and
estuarine organisms are limited. Among effect studies, the vast majority examines
subcellular or cellular effects, with far fewer studies examining organismal- and
community-level effects. We reviewed the current published literature on marine
and estuarine algae, invertebrates, fish, and mammals exposed to PPCPs, in order
to expand upon current reviews. This paper builds on previous reviews of PPCP
contamination in marine environments, filling prior literature gaps and adding
consideration of ecosystem function and level of knowledge across marine habitat
types. Finally, we reviewed and compiled data gaps suggested by current
researchers and reviewers and propose a multi-level model to expand the focus of
current PPCP research beyond laboratory studies. This model includes examination
of direct ecological effects including food web and disease dynamics,
biodiversity, community composition, and other ecosystem-level indicators of
contaminant-driven change.
PMID- 27617335
TI - Environmental risk assessment of pesticides in the River Madre de Dios, Costa
Rica using PERPEST, SSD, and msPAF models.
AB - This study assesses the ecological risks (ERA) of pesticides to aquatic organisms
in the River Madre de Dios (RMD), which receives surface runoff water from
banana, pineapple, and rice plantations on the Caribbean coast of Costa Rica.
Water samples collected over 2 years at five sites in the RMD revealed a total of
26 pesticides. Their toxicity risk to aquatic organisms was assessed using three
recent ERA models. (1) The PERPEST model showed a high probability (>50 %) of
clear toxic effects of pesticide mixtures on algae, macrophytes, zooplankton,
macroinvertebrates, and community metabolism and a low probability (<50 %) of
clear effects on fish. (2) Species sensitivity distributions (SSD) showed a
moderate to high risk of three herbicides: ametryn, bromacil, diuron and four
insecticides: carbaryl, diazinon, ethoprophos, terbufos. (3) The multi-substance
potentially affected fraction (msPAF) model showed results consistent with
PERPEST: high risk to algae (maximum msPAF: 73 %), aquatic plants (61 %), and
arthropods (25 %) and low risk to fish (0.2 %) from pesticide mixtures. The
pesticides posing the highest risks according to msPAF and that should be
substituted with less toxic substances were the herbicides ametryn, diuron, the
insecticides carbaryl, chlorpyrifos, diazinon, ethoprophos, and the fungicide
difenoconazole. Ecological risks were highest near the plantations and decreased
progressively further downstream. The risk to fish was found to be relatively low
in these models, but water samples were not collected during fish kill events and
some highly toxic pesticides known to be used were not analyzed for in this
study. Further sampling and analysis of water samples is needed to determine
toxicity risks to fish during peaks of pesticide mixture concentrations. The
msPAF model, which estimates the ecological risks of mixtures based on their
toxic modes of action, was found to be the most suitable model to assess toxicity
risks to aquatic organisms in the RMD. The PERPEST model was found to be a strong
tool for screening risk assessments. The SSD approach is useful in deriving water
quality criteria for specific pesticides. This study, through the application of
three ERA models, clearly shows that pesticides used in plantations within the
RMD watershed are expected to have severe adverse effects on most groups of
aquatic organisms and that actions are urgently needed to reduce pesticide
pollution in this high biodiversity ecosystem.
PMID- 27617336
TI - Suppression of interleukin 17 contributes to the immunomodulatory effects of
adipose-derived stem cells in a murine model of systemic lupus erythematosus.
AB - Due to roles in immunoregulation and low immunogenicity, mesenchymal stem cells
have been suggested to be potent regulators of the immune response and may
represent promising treatments for autoimmune disease. Adipose-derived stem cells
(ADSCs), stromal cells derived from adipose tissue, were investigated with
allogeneic ADSCs in B6.MRL/lpr mice, a murine model of systemic lupus
erythematosus (SLE). We intravenously injected allogeneic ADSCs into SLE mice
after disease onset and report that ADSCs reduced anti-ds DNA antibodies in serum
and proteinuria in SLE mice. Also, ADSCs decreased IL-17 and IL-6 expression in
serum of SLE mice. ADSCs alleviated renal damage and inflammatory cell
infiltration and edema of the renal interstitium. Furthermore, ADSCs
significantly downregulated renal IL-17 and CD68 expression, suggesting that
ADSCs suppressed renal inflammation. ADSCs also decreased IL-17 mRNA expression
and increased Foxp3, ROR-gammat and miR-23b mRNA expression in renal tissue in
SLE mice. ADSCs reduced renal protein expression of TAB 2 and IKK-alpha in SLE
mice. Thus, ADSCs may be a novel potential therapy for treating SLE.
PMID- 27617338
TI - Composition Tunability and (111)-Dominant Facets of Ultrathin Platinum-Gold Alloy
Nanowires toward Enhanced Electrocatalysis.
AB - The ability for tuning not only the composition but also the type of surface
facets of alloyed nanomaterials is important for the design of catalysts with
enhanced activity and stability through optimizing both ensemble and ligand
effects. Herein we report the first example of ultrathin platinum-gold alloy
nanowires (PtAu NWs) featuring composition-tunable and (111) facet-dominant
surface characteristics, and the electrocatalytic enhancement for the oxygen
reduction reaction (ORR). PtAu NWs of different bimetallic compositions
synthesized by a single-phase and surfactant-free method are shown to display an
alloyed, parallel-bundled structure in which the individual nanowires exhibit
Boerdijk-Coxeter helix type morphology predominant in (111) facets. Results have
revealed intriguing catalytic correlation with the binary composition, exhibiting
an activity maximum at a Pt:Au ratio of ~3:1. As revealed by high-energy
synchrotron X-ray diffraction and atomic pair distribution function analysis, NWs
of this ratio exhibit a clear shrinkage in interatomic bonding distances. In
comparison with PtAu nanoparticles of a similar composition and degree of
shrinking of atomic-pair distances, the PtAu NWs display a remarkably higher
electrocatalytic activity and stability. The outperformance of NWs over
nanoparticles is attributed to the predominant (111)-type facets on the surface
balancing the contribution of ensemble and ligand effects, in addition to the
composition synergy due to optimal adsorption energies for molecular and atomic
oxygen species on the surface as supported by DFT computation of models of the
catalysts. The findings open up a new pathway to the design and engineering of
alloy nanocatalysts with enhanced activity and durability.
PMID- 27617337
TI - Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer
(PC3) and Melanoma Cancer (A375) Cell Lines.
AB - Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer
stage/aggressiveness, but its role in cancer biology is unclear. We revealed
antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3)
and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of
MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on
cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition,
cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT
derived from transfected PC3 cells did not antagonize cisplatin-induced
cytotoxicity. In conclusion, these results suggest possible association between
high circulating AAT and cisplatin resistance.
PMID- 27617339
TI - Remote Activation of Disarmed Thioglycosides in Latent-Active Glycosylation via
Interrupted Pummerer Reaction.
AB - S-glycosides, S-2-(2-propylthio)benzyl (SPTB) glycosides, were converted to the
corresponding oxidized glycosyl donors, S-2-(2-propylsulfinyl)benzyl (SPSB)
glycosides, by simple and selective oxidation. Treatment of disarmed SPSB donor
and various acceptors with triflic anhydride provided the desired glycosides in
good to excellent yields. Meanwhile, observation of thiosulfinate, thiosulfonate,
and disulfide suggested that the leaving group was activated via an interrupted
Pummerer reaction. The disarmed SPSB thioglycosyl donors could be selectively
activated in the presence of various thioglycosides with remote activation mode.
Finally, two natural hepatoprotective glycosides, Leonoside E and Leonuriside B,
were efficiently synthesized in a convergent manner with this newly developed
method.
PMID- 27617340
TI - Refined Parameterization of Nonbonded Interactions Improves Conformational
Sampling and Kinetics of Protein Folding Simulations.
AB - Recent advances in computational technology have enabled brute-force molecular
dynamics (MD) simulations of protein folding using physics-based molecular force
fields. The extensive sampling of protein conformations afforded by such
simulations revealed, however, considerable compaction of the protein
conformations in the unfolded state, which is inconsistent with experiment. Here,
we show that a set of surgical corrections to nonbonded interactions between
amine nitrogen-carboxylate oxygen and aliphatic carbon-carbon atom pairs can
considerably improve the realism of protein folding simulations. Specifically, we
show that employing our corrections in ~500 MUs all-atom replica-exchange MD
simulations of the WW domain and villin head piece proteins increases the size of
the denatured proteins' conformations and does not destabilize the native
conformations of the proteins. In addition to making the folded conformations a
global minimum of the respective free energy landscapes at room temperature, our
corrections also make the free energy landscape smoother, considerably
accelerating the folding kinetics and, hence, reducing the computational expense
of a protein folding simulation.
PMID- 27617341
TI - Design of Ru(II) Complexes Based on Anthraimidazoledione-Functionalized
Terpyridine Ligand for Improvement of Room-Temperature Luminescence
Characteristics and Recognition of Selective Anions: Experimental and DFT/TD-DFT
Study.
AB - In this work we report synthesis and characterization of three rigid and linear
rodlike monometallic Ru(II) complexes based on a terpyridine ligand tightly
connected to 9,10-anthraquinone electron-acceptor unit through phenyl-imidazole
spacer. The motivation of designing these complexes is to enhance their excited
state lifetimes at room temperature. Interestingly it is found that all three
complexes exhibit luminescence at room temperature with excited-state lifetimes
in the range of 1.6-52.8 ns, depending upon the coligand as well as the solvent.
Temperature-dependent luminescence investigations indicate that the energy gap
between the emitting 3MLCT state and nonemitting metal-centered state 3MC in the
complexes increased enormously compared with parent [Ru(tpy)2]2+. In addition, by
taking advantage of the imidazole NH proton(s), which became appreciably acidic
upon combined effect of electron accepting anthraquinone moiety as well as metal
ion coordination, we also examined anion recognition and sensing behaviors of the
complexes in organic, mixed aqueous-organic as well as in solid medium through
different optical channels such as absorption, steady-state and time-resolved
emission, and 1H NMR spectroscopic techniques. In conjunction with the
experiment, computational investigation was also employed to examine the
electronic structures of the complexes and accurate assignment of experimentally
observed spectral and redox behaviors.
PMID- 27617342
TI - Effects of Source and Concentration on Relative Oral Bioavailability of
Benzo(a)pyrene from Soil.
AB - The objective of this study was to examine the influence of soil composition, PAH
concentration, and source material type on PAH bioavailability using an approach
capable of measuring uptake at low, environmentally relevant PAH concentrations
(down to 1 ppm). Contaminated soil samples were constructed using PAHs from three
source materials-solvent, soot, and fuel oil-to which 3H-benzo(a)pyrene (3H-BaP;
total BaP concentrations of 1, 10, and 100 ppm) was added in a mixture of PAHs.
The soils were weathered for 8 weeks using weekly wet-dry cycles. Each soil was
administered as a single dose to rats, and blood samples were taken over 6 days.
Relative oral bioavailability (RBA) of the BaP from soil was estimated by
comparing the area under the curve (AUC) for 3H concentration versus time in
blood with the AUC observed from the same PAH mixture dosed in a food matrix. The
extent to which BaP RBA was diminished in soil versus food varied among the
source materials, but little or no difference was observed among the soil types
examined unless carbon amendments were added. These results suggest that the type
of PAH source material can have a strong influence on PAH oral bioavailability.
PMID- 27617344
TI - Graphitic Carbon Nitride from Burial to Re-emergence on Polyethylene
Terephthalate Nanofibers as an Easily Recycled Photocatalyst for Degrading
Antibiotics under Solar Irradiation.
AB - For powder catalysts to be recycled easily and to be applied in practical
wastewater treatment, it is imperative to search suitable carriers that can be
applied to support catalytic particles. Herein, we highlight a facile route to
synthesize an easily recycled photocatalyst using polyethylene terephthalate
(PET) to disperse graphitic carbon nitride (g-C3N4) via electrospinning and
subsequent hydrothermal treatment. The resultant nanofiber is labeled T-g
C3N4/PET. The design concept is to expose the g-C3N4 on the PET surface and
convert it from inactivation to re-emergence. g-C3N4 is embedded into the PET,
which avoids the reunion and unrecyclable deficiencies of powder catalysts. T-g
C3N4/PET was characterized by field-emission scanning electronic microscopy,
transmission electron microscopy, UV-vis diffuse reflectance spectra, two
dimensional X-ray diffraction, Fourier-transform infrared spectroscopy, and
thermogravimetric analysis technologies. T-g-C3N4/PET showed a high
photocatalytic activity for the degradation of antibiotics such as
sulfaquinoxaline and sulfadiazine under solar irradiation, and the activity was
almost unaffected in a high background. The as-obtained catalysts could be reused
several times with no loss in performance in cycling photodegradation tests.
Finally, a possible pathway and mechanism for degrading sulfaquinoxaline with T-g
C3N4/PET was proposed, respectively, in which holes and the superoxide radical
were the predominant active species, and resulted in the oxidative degradation of
antibiotics. These results demonstrate that the preparation method may provide a
novel idea for supporting nanoscale catalysts for reuse.
PMID- 27617343
TI - Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine
Binding Site.
AB - CCL21 chemokine binds the G protein-coupled receptor CCR7, aiding not only in
immune response but also in cancer metastasis. Compared with other chemokines,
CCL21 has a unique extended unstructured C-terminus that is truncated in some
naturally occurring variants. We have determined the X-ray crystallographic
structure of a truncated CCL21 (residues 1-79) lacking the extended C-terminus
and identified, via two-dimensional nuclear magnetic resonance (NMR), a putative
sulfotyrosine-binding site that may recognize such post-translationally modified
tyrosine residues on the receptor. Compared to the previously determined NMR
structure of full-length CCL21, the crystal structure presents new druggable
binding hot spots resulting from an alternative N-loop conformation. In addition,
whereas the previous NMR structure did not provide any structural information
after residue 70, the C-terminus of the truncated CCL21, ordered up to Ala77 in
our crystal structure, is placed near the N-loop and sulfotyrosine-binding site,
indicating that the extended C-terminus of full-length CCL21 can interact with
this important region for receptor binding. These observations suggest a
potential origin for the autoinhibition of CCL21 activity that was recently
described. The new crystal structure and binding hot spot analysis have important
implications for the function of the CCL21 C-terminus and drug discovery.
PMID- 27617345
TI - Highly Selective and Sensitive Electrochemical Immunoassay of Cry1C Using
Nanobody and pi-pi Stacked Graphene Oxide/Thionine Assembly.
AB - Cry1C is one of the emerging toxin proteins produced by the Bacillus
thuringiensis in the genetically modified crops for pest control in agriculture;
thus, it is vital to measure the Cry1C level in crops for the healthy and
environmental concerns. Current detections of Cry1C mainly rely on instrumental
analysis such as high-performance liquid chromatography, which are time-consuming
and are generally cost-prohibitive. Herein, a simple nanobodies (Nbs)-based
electrochemical immunosensor has been first proposed for highly selective and
sensitive detection of Cry1C. The Nbs pair, i.e., Nb51 and Nb54, which bind to
different epitopes on Cry1C, was screened out from an immunized Bactrian camel,
with an extra benefit of higher stability compared with conventional antibodies.
Further, by using a pi-pi stacked graphene oxide/thionine assembly that had fast
electron transfer kinetics as an electroactive label, the immunoreaction that
occurred between the two Nbs and Cry1C can be highly sensitively quantified by
square wave voltammetry. The linear detection range was from 0.01 to 100 ng.mL-1,
and the low detection limit was 3.2 pg.mL-1. This method was further successfully
applied for sensing Cry 1C in spiked samples with recoveries ranging from 100.17%
to 106.69% and relative standard deviation less than 4.62%. This proposed assay
would provide a simple highly sensitive and selective approach for the Cry1C
toxin detection and be applicable to be extended to other toxin proteins sensing
in foods.
PMID- 27617346
TI - Iodine/Copper Iodide-Mediated C-H Functionalization: Synthesis of Imidazo[1,2
a]pyridines and Indoles from N-Aryl Enamines.
AB - A practical intramolecular C-H functionalization reaction of N-aryl enamines has
been carried out with molecular iodine (I2) as the sole oxidant in the presence
of copper iodide (CuI). The efficient and versatile synthetic method described
here is compatible with both N-heteroaryl and N-aryl substituted enamines and
produces diverse imidazo[1,2-a]pyridine and indole derivatives via I2-mediated
oxidative C-N and C-C bond formation, respectively. This ligand-free C-H
functionalization methodology also works well with crude enamines, which allows
for the sequential synthesis of the products directly from arylamines and ketones
(or alkynes) without purification of the enamine intermediates.
PMID- 27617347
TI - A general model framework for multisymbol number comparison.
AB - Different models have been proposed for the processing of multisymbol numbers
like two- and three-digit numbers but also for negative numbers and decimals.
However, these multisymbol numbers are assembled from the same set of Arabic
digits and comply with the place-value structure of the Arabic number system.
Considering these shared properties, we suggest that the processing of
multisymbol numbers can be described in one general model framework. Accordingly,
we first developed a computational model framework realizing componential
representations of multisymbol numbers and evaluated its validity by simulating
standard empirical effects of number magnitude comparison. We observed that the
model framework successfully accounted for most of these effects. Moreover, our
simulations provided first evidence supporting the notion of a fully componential
processing of multisymbol numbers for the specific case of comparing two negative
numbers. Thus, our general model framework indicates that the processing of
different kinds of multisymbol integer and decimal numbers shares common
characteristics (e.g., componential representation). The relevance and
applicability of our model goes beyond the case of basic number processing. In
particular, we also successfully simulated effects from applied marketing and
consumer research by accounting for the left-digit effect found in processing of
prices. Finally, we provide evidence that our model framework can be integrated
into the more general context of multiattribute decision making. In sum, this
indicates that our model framework captures a general scheme of separate
processing of different attributes weighted by their saliency for the task at
hand. (PsycINFO Database Record
PMID- 27617348
TI - VHL Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single
Typical Manifestations of Type 1 von Hippel-Lindau Disease.
AB - AIMS: von Hippel-Lindau (VHL) disease is caused by mutations in the VHL tumor
suppressor gene. As tumors that develop in the context of VHL also occur in a
sporadic context, the frequency of this syndrome may be underestimated. Our aim
was to identify VHL gene mutations in Argentinian patients who fulfilled the
clinical criteria for type 1 VHL disease and in patients with VHL-associated
manifestations that did not meet these criteria. METHODS: We performed a
retrospective cohort study, including patients who met current diagnostic
criteria for type 1 VHL (Group 1, n = 19) and patients with VHL-associated
manifestations that did not meet these criteria (Group 2, n = 21). Genomic DNA
was extracted from peripheral blood leukocytes. Mutation analysis involved DNA
sequencing, while large deletions were determined by universal primer
quantitative fluorescent multiplex polymerase chain reaction (UPQFM-PCR) and
multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: VHL
mutations were detected in 16/19 (84.2%) patients in Group 1 and included: gross
deletions (4/16); nonsense mutations (6/16); frameshift mutations (4/16);
missense mutations (1/16); and splicing mutations (1/16). Three of these
mutations were novel. No alterations were found in 3 of 19 VHL patients. In Group
2, one nonsense VHL mutation was detected in a young patient with a solitary
central nervous system hemangioblastoma without familial history. A study of 30
first-degree relatives revealed four carriers with VHL mutations. CONCLUSIONS: We
found three novel mutations in the VHL gene in our population. Our results
emphasize the importance of a complete genetic study of VHL to confirm type 1 VHL
disease, not only in patients with clinical diagnostic criteria but also in those
presenting a single typical manifestation.
PMID- 27617349
TI - Theory of Mind in Substance Users: A Systematic Minireview.
AB - BACKGROUND: Theory of mind concerns the sociocognitive ability to infer others'
thoughts. It has been theorized to be impaired in substance use and abuse, as its
alterations might explain negative social and interpersonal outcomes noted in the
course of disorders. In addition, the brain structures involved in Theory of Mind
(ToM) have been found to be disrupted in drug use conditions. OBJECTIVE: We
undertook a systematic review of ToM functioning in drug use conditions. METHODS:
Four electronic databases (MEDLINE, Web of Science, PsycINFO, and Embase) were
searched to find studies that have addressed ToM and conditions related to actual
or previous drug use. RESULTS: The search found 147 papers, of which 14 fulfilled
our review eligibility criteria. Different methods were used, but overall,
results indicated that drugs are related to ToM deficits, particularly related to
alcohol and amphetamines use. These impairments correlate with other clinical and
cognitive functions. CONCLUSION: Despite the lack of studies and the
methodological limitations of the existing ones Theory of Mind seems to play a
role in drug use conditions, which requires further investigation.
PMID- 27617350
TI - Morphology-Controlled Synthesis and Metalation of Porphyrin Nanoparticles with
Enhanced Photocatalytic Performance.
AB - The design and engineering of the size, shape, and chemistry of photoactive
building blocks enables the fabrication of functional nanoparticles for
applications in light harvesting, photocatalytic synthesis, water splitting,
phototherapy, and photodegradation. Here, we report the synthesis of such
nanoparticles through a surfactant-assisted interfacial self-assembly process
using optically active porphyrin as a functional building block. The self
assembly process relies on specific interactions such as pi-pi stacking and
metalation (metal atoms and ligand coordination) between individual porphyrin
building blocks. Depending on the kinetic conditions and type of surfactants,
resulting structures exhibit well-defined one- to three-dimensional morphologies
such as nanowires, nanooctahedra, and hierarchically ordered internal
architectures. Specifically, electron microscopy and X-ray diffraction results
indicate that these nanoparticles exhibit stable single-crystalline and
nanoporous frameworks. Due to the hierarchical ordering of the porphyrins, the
nanoparticles exhibit collective optical properties resulted from coupling of
molecular porphyrins and photocatalytic activities such as photodegradation of
methyl orange (MO) pollutants and hydrogen production.
PMID- 27617351
TI - How can we maximize the use of our operating lists? An analysis of factors
influencing theatre efficiency in oculoplastic day surgery.
AB - Operating theatre utilization has become the principal measure of NHS operating
theatre service performance. We analysed data from oculoplastic theatres in a
tertiary centre to identify factors influencing theatre efficiency. We conducted
three audits on operating theatre utilization in 2011, 2014 and 2015. Data was
collected from real time information entered into the hospital database,
including time of arrival, induction, first cut and close of operation. The
primary outcome measure was the operating list utilization rate, a combined value
of anaesthetic and surgical time as a proportion of the total planned session
time. The initial 2011 audit recorded an operating list utilization rate of
81.2%. However, this dropped to 64.5% in 2014 following new management and a move
to a new theatre suite. Analysis of the factors contributing to poor theatre
efficiency led to changes that streamlined the patient pathway, including
standardized case scheduling and reducing staggered patient arrival. A 2015
reaudit analyzing the effects of these changes demonstrated an increase in the
operating list utilization rate to 78%. It was significantly higher (p < 0.01)
for whole-day lists (85%) compared to half-day lists (75%), suggesting that whole
day lists were more efficient. Operating theatres are a valuable resource and the
factors affecting theatre efficiency within our unit are common and will be
relevant to units elsewhere. Correcting them can lead to significant improvements
in patient care. Data from this study may provide a benchmark for other units in
the United Kingdom.
PMID- 27617352
TI - Zika Virus Infection in the Central Nervous System and Female Genital Tract.
PMID- 27617354
TI - Invented spelling in kindergarten as a predictor of reading and spelling in Grade
1: A new pathway to literacy, or just the same road, less known?
AB - In this study we evaluated whether the sophistication of children's invented
spellings in kindergarten was predictive of subsequent reading and spelling in
Grade 1, while also considering the influence of well-known precursors. Children
in their first year of schooling (mean age = 66 months; N = 171) were assessed on
measures of oral vocabulary, alphabetic knowledge, phonological awareness, word
reading and invented spelling; approximately 1 year later they were assessed on
multiple measures of reading and spelling. Path modeling was pursued to evaluate
a hypothesized unique, causal role of invented spelling in subsequent literacy
outcomes. Results supported a model in which invented spelling contributed
directly to concurrent reading along with alphabetic knowledge and phonological
awareness. Longitudinally, invented spelling influenced subsequent reading, along
with alphabetic knowledge while mediating the connection between phonological
awareness and early reading. Invented spelling also influenced subsequent
conventional spelling along with phonological awareness, while mediating the
influence of alphabetic knowledge. Invented spelling thus adds explanatory
variance to literacy outcomes not entirely captured by well-studied code and
language-related skills. (PsycINFO Database Record
PMID- 27617353
TI - Metabolism and Residues of 2,4-Dichlorophenoxyacetic Acid in DAS-40278-9 Maize
(Zea mays) Transformed with Aryloxyalkanoate Dioxygenase-1 Gene.
AB - DAS-40278-9 maize, which is developed by Dow AgroSciences, has been genetically
modified to express the aryloxyalkanoate dioxygenase-1 (AAD-1) protein and is
tolerant to phenoxy auxin herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4
D). To understand the metabolic route and residue distribution of 2,4-D in DAS
40278-9 maize, a metabolism study was conducted with 14C-radiolabeled 2,4-D
applied at the maximum seasonal rate. Plants were grown in boxes outdoors. Forage
and mature grain, cobs, and stover were collected for analysis. The metabolism
study showed that 2,4-D was metabolized to 2,4-dichlorophenol (2,4-DCP), which
was then rapidly conjugated with glucose. Field-scale residue studies with 2,4-D
applied at the maximum seasonal rate were conducted at 25 sites in the U.S. and
Canada to measure the residues of 2,4-D and free and conjugated 2,4-DCP in mature
forage, grain, and stover. Residues of 2,4-D were not detectable in the majority
of the grain samples and averaged <1.0 and <1.5 MUg/g in forage and stover,
respectively. Free plus conjugated 2,4-DCP was not observed in grain and averaged
<1.0 MUg/g in forage and stover.
PMID- 27617355
TI - A short German Physical-Self-Concept Questionnaire for elementary school children
(PSCQ-C): Factorial validity and measurement invariance across gender.
AB - Research on children's physical self-concept (PSC) is increasingly recognised as
an important field of psychology. However, there is a lack of instruments
suitable for younger children at elementary school age. In the present study, a
short German 21-item Physical Self-Concept-Questionnaire for children (PSCQ-C)
was tested measuring seven specific facets of elementary school children's PSC
(strength, endurance, speed, flexibility, coordination, physical appearance,
global sport competence). A number of 770 elementary school children aged 8-12
years completed the PSCQ-C. Results showed good psychometric properties and high
reliabilities of the seven scales. Confirmatory factor analysis revealed that the
presumed 7-factor model fitted the data best compared to a global 1- and 2-factor
model. Also, full measurement invariance was strongly established. Correlations
among the seven scales were mainly moderate. Gender differences were suggestive
of developmental trends that are consistent with prior studies. These results
provide support that the PSCQ-C is a confidential instrument with sound
psychometric properties measuring seven specific facets of elementary school
children's PSC.
PMID- 27617357
TI - Ontogenetic Scaling of Theoretical Bite Force in Southern Sea Otters (Enhydra
lutris nereis).
AB - Sexual dimorphism attributed to niche divergence is often linked to
differentiation between the sexes in both dietary resources and characters
related to feeding and resource procurement. Although recent studies have
indicated that southern sea otters (Enhydra lutris nereis) exhibit differences in
dietary preferences as well as sexual dimorphism in skull size and shape, whether
these intersexual differences translate to differentiation in feeding
performances between the sexes remains to be investigated. To test the hypothesis
that scaling patterns of bite force, a metric of feeding performance, differ
between the sexes, we calculated theoretical bite forces for 55 naturally
deceased male and female southern sea otters spanning the size ranges encountered
over ontogeny. We then used standardized major axis regressions to simultaneously
determine the scaling patterns of theoretical bite forces and skull components
across ontogeny and assess whether these scaling patterns differed between the
sexes. We found that positive allometric increases in theoretical bite force
resulted from positive allometric increases in physiological cross-sectional area
for the major jaw adductor muscle and mechanical advantage. Closer examination
revealed that allometric increases in temporalis muscle mass and relative
allometric decreases in out-lever lengths are driving these patterns. In our
analysis of sexual dimorphism, we found that scaling patterns of theoretical bite
force and morphological traits do not differ between the sexes. However, adult
sea otters differed in their absolute bite forces, revealing that adult males
exhibited greater bite forces as a result of their larger sizes. We found
intersexual differences in biting ability that provide some support for the niche
divergence hypothesis. Continued work in this field may link intersexual
differences in feeding functional morphology with foraging ecology to show how
niche divergence has the potential to reinforce sexual dimorphism in southern sea
otters.
PMID- 27617356
TI - Addressing Barriers to Shared Decision Making Among Latino LGBTQ Patients and
Healthcare Providers in Clinical Settings.
AB - Effective shared decision making (SDM) between patients and healthcare providers
has been positively associated with health outcomes. However, little is known
about the SDM process between Latino patients who identify as lesbian, gay,
bisexual, transgender, or queer (LGBTQ), and their healthcare providers. Our
review of the literature identified unique aspects of Latino LGBTQ persons'
culture, health beliefs, and experiences that may affect their ability to engage
in SDM with their healthcare providers. Further research needs to examine Latino
LGBTQ patient-provider experiences with SDM and develop tools that can better
facilitate SDM in this patient population.
PMID- 27617358
TI - Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and
Preservation of Bone Architecture and Strength in Hibernating Marmots.
AB - Periods of physical inactivity increase bone resorption and cause bone loss and
increased fracture risk. However, hibernating bears, marmots, and woodchucks
maintain bone structure and strength, despite being physically inactive for
prolonged periods annually. We tested the hypothesis that bone turnover rates
would decrease and bone structural and mechanical properties would be preserved
in hibernating marmots (Marmota flaviventris). Femurs and tibias were collected
from marmots during hibernation and in the summer following hibernation. Bone
remodeling was significantly altered in cortical and trabecular bone during
hibernation with suppressed formation and no change in resorption, unlike the
increased bone resorption that occurs during disuse in humans and other animals.
Trabecular bone architecture and cortical bone geometrical and mechanical
properties were not different between hibernating and active marmots, but bone
marrow adiposity was significantly greater in hibernators. Of the 506 proteins
identified in marmot bone, 40 were significantly different in abundance between
active and hibernating marmots. Monoaglycerol lipase, which plays an important
role in fatty acid metabolism and the endocannabinoid system, was 98-fold higher
in hibernating marmots compared with summer marmots and may play a role in
regulating the changes in bone and fat metabolism that occur during hibernation.
PMID- 27617359
TI - Mass Loss Rates of Fasting Polar Bears.
AB - Polar bears (Ursus maritimus) have adapted to an annual cyclic regime of feeding
and fasting, which is extreme in seasonal sea ice regions of the Arctic. As a
consequence of climate change, sea ice breakup has become earlier and the
duration of the open-water period through which polar bears must rely on fat
reserves has increased. To date, there is limited empirical data with which to
evaluate the potential energetic capacity of polar bears to withstand longer
fasts. We measured the incoming and outgoing mass of inactive polar bears (n =
142) that were temporarily detained by Manitoba Conservation and Water
Stewardship during the open-water period near the town of Churchill, Manitoba,
Canada, in 2009-2014. Polar bears were given access to water but not food and
held for a median length of 17 d. Median mass loss rates were 1.0 kg/d, while
median mass-specific loss rates were 0.5%/d, similar to other species with high
adiposity and prolonged fasting capacities. Mass loss by unfed captive adult
males was identical to that lost by free-ranging individuals, suggesting that
terrestrial feeding contributes little to offset mass loss. The inferred
metabolic rate was comparable to a basal mammalian rate, suggesting that while on
land, polar bears can maintain a depressed metabolic rate to conserve energy.
Finally, we estimated time to starvation for subadults and adult males for the on
land period. Results suggest that at 180 d of fasting, 56%-63% of subadults and
18%-24% of adult males in this study would die of starvation. Results corroborate
previous assessments on the limits of polar bear capacity to withstand
lengthening ice-free seasons and emphasize the greater sensitivity of subadults
to changes in sea ice phenology.
PMID- 27617360
TI - Consequences of Food Restriction for Immune Defense, Parasite Infection, and
Fitness in Monarch Butterflies.
AB - Organisms have a finite pool of resources to allocate toward multiple competing
needs, such as development, reproduction, and enemy defense. Abundant resources
can support investment in multiple traits simultaneously, but limited resources
might promote trade-offs between fitness-related traits and immune defenses. We
asked how food restriction at both larval and adult life stages of the monarch
butterfly (Danaus plexippus) affected measures of immunity, fitness, and immune
fitness interactions. We experimentally infected a subset of monarchs with a
specialist protozoan parasite to determine whether parasitism further affected
these relationships and whether food restriction influenced the outcome of
infection. Larval food restriction reduced monarch fitness measures both within
the same life stage (e.g., pupal mass) as well as later in life (e.g., adult
lifespan); adult food restriction further reduced adult lifespan. Larval food
restriction lowered both hemocyte concentration and phenoloxidase activity at the
larval stage, and the effects of larval food restriction on phenoloxidase
activity persisted when immunity was sampled at the adult stage. Adult food
restriction reduced only adult phenoloxidase activity but not hemocyte
concentration. Parasite spore load decreased with one measure of larval immunity,
but food restriction did not increase the probability of parasite infection.
Across monarchs, we found a negative relationship between larval hemocyte
concentration and pupal mass, and a trade-off between adult hemocyte
concentration and adult life span was evident in parasitized female monarchs.
Adult life span increased with phenoloxidase activity in some subsets of
monarchs. Our results emphasize that food restriction can alter fitness and
immunity across multiple life stages. Understanding the consequences of resource
limitation for immune defense is therefore important for predicting how
increasing constraints on wildlife resources will affect fitness and resistance
to natural enemies.
PMID- 27617361
TI - Changes to Intestinal Transport Physiology and Carbonate Production at Various
CO2 Levels in a Marine Teleost, the Gulf Toadfish (Opsanus beta).
AB - Most marine teleosts defend blood pH during high CO2 exposure by sustaining
elevated levels of HCO3(-) in body fluids. In contrast to the gill, where
measures are taken to achieve net base retention, elevated CO2 leads to base loss
in the intestine of marine teleosts studied to date. This loss is thought to
occur through transport pathways previously demonstrated to be involved with
routine osmoregulation in marine teleosts. The main objective of this study was
to characterize the intestinal transport physiology of the gulf toadfish (Opsanus
beta) when exposed to varied levels of CO2: control, 5,000, 10,000, and 20,000
MUatm CO2 (0.04, 0.5, 1, and 2 kPa, respectively). Results of this study suggest
that intestinal apical anion exchange is highly responsive to hypercarbia,
evidenced by a dose-dependent increase in intestinal luminal HCO3(-) (mmol L(-1))
that was mirrored by a reduction in Cl(-) (mmol L(-1)). Despite activation of
HCO3(-) transport pathways typically used during osmoregulation, fractional fluid
absorption was only significantly lower at the highest level of CO2. Although
increased HCO3(-) excretion could provide more substrate for intestinally
produced carbonates, carbonate production was not significantly increased during
hypercarbia at the levels tested. This study is among the first to thoroughly
characterize how compensation for elevated CO2 affects transport physiology and
carbonate production in the marine fish intestine. This deeper understanding may
be particularly relevant when considering the impacts of future predicted ocean
acidification, where prolonged base loss may alter the energetic cost of acid
base balance or osmoregulation in marine fish.
PMID- 27617362
TI - Variation in the Markers of Nutritional and Oxidative State in a Long-Lived
Seabird: Associations with Age and Longevity.
AB - Age-related declines in life-history traits have been widely observed in free
living animals. Several theories link senescence to oxidative stress. The aim of
this study was to measure several widely used markers of oxidative and
nutritional state in a long-lived seabird, the common gull (Larus canus), in
order to assess the suitability of these markers for describing deterioration in
physiological condition associated with chronological age and survival.
Associations with longevity and individual consistency of these parameters over
the years (repeatability) were also assessed. Senescence in fitness parameters
was observed during the study period: in females, laying date and clutch mass
were related to bird age in a curvilinear manner, with middle-aged birds breeding
earlier and laying heavier eggs. The only parameter associated with aging
processes was glutathione concentration in erythrocytes, which was lower in
female birds with longer life spans. Of indexes of nutritional state, plasma
triglyceride concentration showed a between-individual increase with age,
suggesting selective mortality of birds with low levels. Additionally, total
plasma protein levels of individual males increased with age. The mostly negative
results of this study hint that the commonly used parameters of physiological
condition and oxidative state used in this study do not adequately reflect an
individual's long-term health condition. Alternatively, it is possible that in
common gulls, senescence occurs in reproductive mechanisms but not in mechanisms
responsible for maintaining an organism's redox balance, consistent with the idea
that different aspects of an organism's physiological condition age at different
rates. Significant interannual repeatability was detected in three plasma
constituents-carotenoids, uric acid, and total protein-all of which can possibly
be linked to variation in dietary habits.
PMID- 27617363
TI - Age and Heat Stress as Determinants of Telomere Length in a Long-Lived Fish, the
Siberian Sturgeon.
AB - Telomeres shorten at each cell division due to the end-replication problem but
also in response to oxidative stress. Consequently, telomeres shorten with age in
many endotherms, and this shortening is accelerated under stressful environmental
conditions. Data in ectotherm vertebrates remain scarce so far, so our goal was
to review existing data for fish and to test the influence of age and stress on
telomere length in a very long-lived fish, the Siberian sturgeon (Acipenser
baerii). Our review of the literature revealed age-related telomere shortening in
approximately half of the published studies. In the Siberian sturgeon, we found a
significant telomere shortening with age, both at the intraindividual level using
red blood cells (-12.5% in 16 mo) and at the interindividual level using cross
sectional samples of fin over an age range of 8 yr. We also found that heat
stress (30 degrees C) significantly reduced telomere length by 15.0% after only 1
mo of exposure. Our results highlight that both age and stressful environmental
conditions might be important determinants of telomere length in fish.
PMID- 27617364
TI - High Yolk Testosterone Transfer Is Associated with an Increased Female Metabolic
Rate.
AB - Yolk androgens of maternal origin are important mediators of prenatal maternal
effects. Although in many species short-term benefits of exposure to high yolk
androgen concentrations for the offspring have been observed, females differ
substantially in the amount of androgens they transfer to their eggs. It suggests
that costs for the offspring or the mother constrain the evolution of maternal
hormone transfer. However, to date, the nature of these costs remains poorly
understood. Unlike most previous work that focused on potential costs for the
offspring, we here investigated whether high yolk testosterone transfer is
associated with metabolic costs (i.e., a higher metabolic rate) for the mother.
We show that Japanese quail (Coturnix japonica) females that deposit higher
testosterone concentrations into their eggs have a higher resting metabolic rate.
Because a higher metabolic rate is often associated with a shorter life span,
this relationship may explain the negative association between yolk testosterone
transfer and female longevity observed in the wild. Our results suggest that
metabolic costs for the mother can balance the short-term benefits of yolk
testosterone exposure for the offspring, thereby contributing to the maintenance
of variation in maternal yolk hormone transfer in natural populations.
PMID- 27617367
TI - Combination Therapies for Smoking Cessation: A Hierarchical Bayesian Meta
Analysis.
AB - CONTEXT: Treatment guidelines recommend the use of combination therapies for
smoking cessation, particularly behavioral therapy (BT) as an adjunct to
pharmacotherapy. However, these guidelines rely on previous reviews with
important limitations. This study's objective was to evaluate the efficacy of
combination therapies compared with monotherapies, using the most rigorous data
available. EVIDENCE ACQUISITION: A systematic review and meta-analysis of RCTs of
pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase,
PsycINFO, and PubMed databases were systematically searched from inception to
July 2015. Inclusion was restricted to RCTs reporting biochemically validated
abstinence at 12 months. Direct and indirect comparisons were made in 2015
between therapies using hierarchical Bayesian models. EVIDENCE SYNTHESIS: The
search identified 123 RCTs meeting inclusion criteria (60,774 participants), and
data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT
increased abstinence more than other combinations of a pharmacotherapy with BT
(varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34;
varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline
versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53).
Adding BT to any pharmacotherapy compared with pharmacotherapy alone was
inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with
short-acting nicotine-replacement therapy appears safe and increases abstinence
versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are
limited concerning other pharmacotherapy combinations and their safety and
tolerability. CONCLUSIONS: Evidence suggests that combination therapy benefits
may be less than previously thought. Combined with BT, varenicline increases
abstinence more than other pharmacotherapy with BT combinations.
PMID- 27617366
TI - The Influence of Sugar-Sweetened Beverage Warnings: A Randomized Trial of
Adolescents' Choices and Beliefs.
AB - INTRODUCTION: California, New York, and the cities of San Francisco and Baltimore
have introduced bills requiring health-related warning labels for sugar-sweetened
beverages. This study measures the extent to which these warning labels influence
adolescents' beliefs and hypothetical choices. DESIGN: Participants completed an
online survey in which they chose a beverage in a hypothetical vending machine
task, rated perceptions of different beverages, and indicated interest in coupons
for beverages. Data were collected and analyzed in 2015. SETTING/PARTICIPANTS: A
total of 2,202 demographically diverse adolescents aged 12-18 years completed the
online survey. INTERVENTION: Participants were randomly assigned to one of six
conditions: (1) no warning label; (2) calorie label; (3-6) one of four text
versions of a warning label (e.g. , SAFETY WARNING: Drinking beverages with added
sugar(s) contributes to obesity, diabetes, and tooth decay). MAIN OUTCOME
MEASURES: Hypothetical choices, perceptions of beverages, interest in coupons,
and endorsement of warning label policies were assessed. RESULTS: Controlling for
frequency of beverage purchases, significantly fewer adolescents chose a sugar
sweetened beverage in three of the four warning label conditions (65%, 63%, and
61%) than in the no label (77%) condition. Adolescents in the four warning label
conditions chose fewer sugar-sweetened beverage coupons and believed that sugar
sweetened beverages were less likely to help them lead a healthy life and had
more added sugar compared with the no label condition. CONCLUSIONS: Health
related warning labels on sugar-sweetened beverages improved adolescents'
recognition of the sugar content of such beverages and reduced hypothetical
choices to buy sugar-sweetened beverages.
PMID- 27617368
TI - Patient Factors Influencing Respiratory-Related Clinician Actions in Chronic
Obstructive Pulmonary Disease Screening.
AB - INTRODUCTION: The purpose of this study was to identify patient-related factors
that may explain the increased likelihood of receiving a respiratory-related
clinician action in patients identified to be at risk for chronic obstructive
pulmonary disease in a U.S.-based pragmatic study of chronic obstructive
pulmonary disease screening. METHODS: This post hoc analysis (conducted in 2014
2015) of the Screening, Evaluating and Assessing Rate Changes of Diagnosing
Respiratory Conditions in Primary Care 1 (SEARCH1) study (conducted in 2010
2011), used the chronic obstructive pulmonary disease Population Screener
questionnaire in 112 primary care practices. Anyone with a previous chronic
obstructive pulmonary disease diagnosis was excluded. Multivariate logistic
regression modeling was used to assess patient factors associated with the
likelihood of receiving an respiratory-related clinician action following
positive screening. RESULTS: Overall, 994 of 6,497 (15%) screened positive and
were considered at risk for chronic obstructive pulmonary disease. However, only
187 of the 994 patients (19%) who screened positive received a respiratory
related clinician action. The chances of receiving a respiratory-related
clinician action were significantly increased in patients who visited their
physician with a respiratory issue (p<0.05) or had already been prescribed a
respiratory medication (p<0.05). Most (81%) patients who screened positive or had
a respiratory-related clinician action had one or more comorbidity, including
cardiovascular disease (68%), diabetes (30%), depression/anxiety (26%), asthma
(11%), and cancer (9%). CONCLUSIONS: Routine chronic obstructive pulmonary
disease screening appears to promote respiratory-related clinician actions in
patients with a high likelihood for disease who have respiratory complaints or
already use prescribed respiratory medication.
PMID- 27617369
TI - Nitrogen regulates CRY1 phosphorylation and circadian clock input pathways.
AB - The delayed flowering phenotype caused by nitrogen (N) fertilizer application has
been known for a long time, but we know little about the specific molecular
mechanism for this phenomenon before. Our study indicated that low nitrogen
increases the NADPH/NADP(+) and ATP/AMP ratios which affect adenosine
monophosphate-activated protein kinase (AMPK) activity and phosphorylation and
abundance of nuclear CRY1 protein. Then CRY1 acts in the N signal input pathway
to the circadian clock. Here we further discuss: (1) the role of C/N ratio in
flowering, (2) circadian oscillation of plant AMPK transcripts and proteins, (3)
conservation of nutrition-mediated CRY1 phosphorylation and degradation, and (4)
crosstalks between nitrogen signals and nitric oxide (NO) signals in flowering.
PMID- 27617370
TI - Contemporary Management of ST-Elevation Myocardial Infarction.
AB - Recent advances have caused a major shift in the way ST-elevation myocardial
infarctions are managed. This review explores the pharmacological and
interventional techniques that have evidence for improving outcomes and the
landmark trials that have sparked change. The new P2Y12 inhibitors, ticagrelor
and prasugrel, have been shown to be superior to clopidogrel in STEMI patients
undergoing primary percutaneous coronary intervention. Concurrently, many
technical aspects of percutaneous coronary intervention have been further
clarified by trial data, with bare-metal stents, routine thrombus aspiration and
femoral access showing evidence of inferiority. Ongoing trials will provide more
information on the role of non-culprit lesion PCI, bioresorbable vascular
scaffolds, mechanical devices in persistent ischaemia and early automatic
implantable cardioverter-defibrillators for inducible ventricular tachycardia.
PMID- 27617372
TI - Pediatric Dentistry Specialty as Part of a Longer Continuum of Care: A
Commentary.
AB - The transition of teenagers with special needs to young adulthood is a complex
period for the children and their families. This transition is especially
difficult when it comes to securing needed oral health care. The teenager is
forced to transfer from the services of an age defined pediatric dental
specialist with training to provide care for individuals with special needs, to
1) general practitioners with limited formal training and often unwillingness to
provide care and 2) at a period when most states provide limited or lack of adult
dental Medicaid programs. These issues and the need to expand pediatric dental
specialist involvement in the general transitional period are reviewed.
"Pediatric dentistry is an age-defined specialty that provides both primary and
comprehensive preventive and therapeutic oral health care for infants and
children through adolescence, including those with special health care needs."(1)
"Our system of preparing and maintaining our abilities to provide oral health
services for an increasing diverse population must be brought up to date to meet
the challenges posed by the treatment of young adults with disabilities."(2)
"Most responding dentists (to a national study of pediatric dentists) helped
adolescents with and without SHCNs (Special Health Care Needs) make the
transition into adult care, but the major barrier was the availability of general
dentists and specialists."(3).
PMID- 27617371
TI - Do GIS-derived measures of fast food retailers convey perceived fast food
opportunities? Implications for food environment assessment.
AB - PURPOSE: Geographic information systems (GISs) have been used to define fast food
availability, with higher availability perhaps promoting poorer quality diets.
Alternative measures involve perceptions; however, few studies have examined
associations between GIS-derived and perceived measures of the food environment.
METHODS: Telephone surveys of 705 participants within an eight-county region in
South Carolina were analyzed using logistic regression to examine relationships
between geographic presence of and distance to various types of food retailers
and perceived fast food availability. RESULTS: The mean distance to the nearest
fast food restaurant was 6.1 miles, with 16% of participants having a fast food
restaurant within 1 mile of home. The geographic presence of and distance to all
food retailer types were significantly associated with perceived availability of
fast food in unadjusted models. After adjustment, only the presence of a fast
food restaurant or pharmacy was significantly associated with greater odds of
higher perceived availability of fast food. Greater odds of lower perceived
availability of fast food were observed with the presence of a dollar store and
increasing distance to the nearest supermarket or pharmacy. CONCLUSIONS: Measures
of fast food availability, whether objective or perceived, may not be
interchangeable. Researchers should carefully decide on the appropriate
measurement tool-GIS-derived or perceived-in food environment studies.
PMID- 27617373
TI - Clinical Performance of Indirect Composite Onlays as Esthetic Alternative to
Stainless Steel Crowns for Rehabilitation of a Large Carious Primary Molar.
AB - OBJECTIVE: The aim of the present study was to evaluate the clinical performance
of indirect resin composite onlays (IRC onlay) compared to stainless steel crowns
(SSCs), as an esthetic alternative for rehabilitation of extensively carious
primary molars. STUDY DESIGN: Fifty pediatric patients each received either IRC
onlay or SSC randomly on extensively carious endodontically treated primary
molars. All the restorations were evaluated at baseline and then every 6 months
till 36 months using 'modified FDI criteria' for retention, marginal integrity,
occlusion, proximal contact, secondary caries and gingival health. The dental
chair side treatment time and post-operative acceptability were also evaluated
for both the groups. RESULTS: The cumulative survival rate of IRC onlays was
82.9% compared to 90.7% for SSCs over a time period of 36 months. The difference
between the two study groups at various time intervals in terms of retention,
marginal integrity, secondary caries, proximal contact, occlusion and gingival
health was not statistically significant (p>0.05). The IRC onlays required
significantly less mean chair side treatment time and were preferred the most by
parents and children as per VAS scores compared to SSCs. CONCLUSION: IRC onlays
are an acceptable esthetic alternative to SSCs and may be considered for use in
aesthetically conscious children/parents as per their preference.
PMID- 27617374
TI - Pink Spot - Literature Review and Case Report.
AB - BACKGROUND: Pink spots in teeth were first described by Mummery in 1920, and were
related to resorption. Resorption is a pathologic process that often eludes the
clinician with its varied etiologic factors and diverse clinical presentations.
Resorption can be generally classified as internal and external resorption.
Internal resorption has been described as a rare occurrence as compared to
external resorption. CASE REPORT: This article describes a pink spot that was
diagnosed as a progressing resorption process. Early diagnosis enabled a
successful management of the lesion. CONCLUSION: Early diagnosis and treatment of
an internal resorption, clinically seen as a pink spot, in a primary central
incisor may prevent its fast progress and subsequent loss.
PMID- 27617375
TI - Regenerative Endodontic Treatment versus Apical Plug in Immature Teeth: Three
Year Follow-Up.
AB - This report compares and evaluates the treatment outcomes of regenerative
endodontic treatment and apical plug as two accepted treatment protocols in a
pair of necrotic immature maxillary central incisors of a 12-year old female. The
patient was referred complaining of a dull pain and swelling in her upper lip
area. She had a history of trauma to the anterior maxilla two years earlier. Both
teeth were clinically diagnosed with pulp necrosis and periapical radiographs
revealed that separate periapical radiolucent lesions surrounded the immature
apices of both teeth. The left and right incisors were treated with apical plug
and regenerative endodontic treatment, respectively, using calcium-enriched
mixture (CEM) cement. The patient was followed-up for three years. During this
period, both teeth were clinically asymptomatic and showed complete radiographic
healing of the periapical lesions. The right central incisor showed root
development. No tooth discoloration was evident. Apexification by apical plug
placement and pulp regeneration are both reliable treatments for immature non
vital teeth. In order to choose the right treatment the advantages of either
technique should be weighed against its drawbacks. CEM cement can be successfully
applied for both purposes. This biomaterial causes less discoloration of the
tooth.
PMID- 27617377
TI - Phenotypes of Enamel Hypomineralization and Molar Incisor Hypomineralization in
Permanent Dentition: Identification, Quantification and Proposal for
Classification.
AB - OBJECTIVES: To report the extent, pattern, clinical presentation and phenotypes
of enamel hypomineralization in permanent dentition Study Design: This cross
sectional observational study recruited a random sample of 1726, 12-16 year olds.
Enamel hypomineralization was scored on all teeth by a calibrated examiner using
the EAPD 2003 criteria. Proportions of affected subjects (prevalence) with a
minimum of one hypomineralization and Molar Incisor Hypomineralization (MIH) were
calculated. Proportions of following phenotypes were quantified i.e. MH (only FPM
hypomineralization), M+IH (concomitantly affected FPMs and permanent incisors
without affecting any other tooth in the arch), MIHO (hypomineralization
affecting at least one of the canines, premolars or 2(nd) molars and
simultaneously including at least one FPM), IH (only permanent incisor's
hypomineralization) and NoFPM (hypomineralization affecting at least one of the
canines, premolars and 2(nd) molars but not FPM; incisors can be affected
concomitantly). A comparative evaluation of extent and severity of enamel
hypomineralization was performed amongst various phenotypes. Statistical measures
employed t-test, chi square tests and ANOVA. RESULTS: Overall prevalence of
affected subjects was 13.21% (228/1726) and 9.79% (169/1726) for enamel
hypomineralization and MIH respectively. A total of 4.36+/-3.45 teeth/subject and
6.01+/-5.20 surfaces/subject were found to be affected with enamel
hypomineralization. Most prevalent phenotype was M+IH while the least prevalent
was IH. Maximum severity i.e. number of affected surfaces and surfaces with PEB
were reported for MIHO (p<0.001). CONCLUSION: Enamel hypomineralization can
manifest in any tooth in five phenotypic variations in permanent dentition with
varying extent and severity.
PMID- 27617376
TI - Dental Pulp Revascularization of Necrotic Permanent Teeth with Immature Apices.
AB - OBJECTIVES: The treatment of immature necrotic teeth with apical periodontitis
presents challenges in endodontic and pediatric dentistry. Revascularization is a
recent treatment for such cases as an alternative to conventional apexification.
The purpose is to examine the effect of a pulpal revascularization procedure on
immature necrotic teeth with apical periodontitis. STUDY DESIGN: Twenty patients
were enrolled for pulp revascularization procedure by root canal disinfection
using a triple antibiotic mixture for 1-2 weeks, followed by creating a blood
clot, sealing the root canal orifice using white mineral trioxide aggregate and a
coronal seal of composite resin. Patients were recalled periodically for up to 24
months. RESULTS: During follow-up, all patients were asymptomatic. Three cases of
chronic apical periodontitis showed clinical disappearance of the sinus tract 2
weeks after treatment. Radiography revealed progressive periapical radiolucency
resolution within the first 12 months. Within 12-24 months, the treated teeth
showed progressive increases in dentinal wall thickness, root length and
continued root development. CONCLUSIONS: Clinical and radiographic evidence
showed successful revascularization treatments of immature necrotic permanent
teeth with apical periodontitis. More studies are necessary to understand the
underlying mechanisms and to perform histopathology of the pulp space contents
after revascularization procedures.
PMID- 27617378
TI - Oral Health Quality of Life in Children with Cerebral Palsy: Parental
Perceptions.
AB - OBJECTIVE: To assess the parents' perception of the oral health-related quality
of life (OHRQOL) in children with Cerebral Palsy (CP) and compare it with
normally developing children. STUDY DESIGN: 63 children with CP were recruited
from 8 disability centers, and 99 healthy controls were recruited from 5
elementary schools. The ages of the children in both groups were from 6-12 years.
The Franciscan Hospital for Children Oral Health-Related Quality of Life (FHC
OHRQOL) was used to measure the OHRQOL and an oral examination was conducted in
the schools/centers of the children to assess the teeth, gingival health, and
oral hygiene. RESULTS: The FHC-OHRQOL showed a significant difference in 3 out of
4 sections indicating lower OHRQOL in the CP group. The examination showed no
significant difference in the dental and gingival health and in the level of oral
hygiene. CONCLUSION: The OHRQOL of children with CP is significantly lower than
that of normally developing children although the oral health status of children
with CP is not significantly different from that of normally developing children.
PMID- 27617379
TI - Clinical Assessment of a New Caries Activity Test Using Dental Plaque
Acidogenicity in Children under Three Years of Age.
AB - OBJECTIVES: The aim of this study was to assess the validity of a new caries
activity test that uses dental plaque acidogenicity in children with deciduous
dentition. STUDY DESIGN: Ninety-two children under the age of three years old
underwent clinical examination using the dft index and examinations with two
caries activity tests. Plaque samples for the new Cariview((r)) test and the
saliva sample for the conventional Dentocult SM((r)) test were collected,
incubated, and scored according to each manufacturers' instruction. The data were
analysed using ANOVA and Spearman correlation analyses to evaluate the
relationships between the test results and the caries experience. RESULTS: The
mean dft index of all of the subjects was 4.73, and 17.4% of the subjects were
caries-free. The levels of caries risk based on the new Cariview test score
significantly increased with the caries experience (p < 0.01). The test results
revealed a stronger correlation with caries indices (dft and dt index) than the
conventional SM colony counting method (r = 0.43, r = 0.39, p < 0.01).
CONCLUSIONS: The new caries activity test to analyse the acidogenic potential of
whole microorganisms from dental plaques can be used to evaluate caries risk in
children with deciduous teeth.
PMID- 27617380
TI - Visual Schedule System in Dental Care for Patients with Autism: A Pilot Study.
AB - OBJECTIVES: A pilot study to test whether a visual schedule system using picture
communication symbols can help children with autism have successful routine
dental cleaning visits. STUDY DESIGN: 14 boys with autism between three- to eight
years-old presented to the dental clinic for four weekly consecutive dental
appointments. Patients were randomly assigned to either the control group who
received the tell-show-do method (i.e., standard of care), or the test group who
received the tell-show-do method plus the visual schedule system. RESULTS:
Patients in the test group completed an average of 1.38 more steps, at 35.52
seconds per step faster, and with 18.7% lower levels of behavioral distress than
those in the control group. CONCLUSION: The use of a visual schedule system,
along with repeated weekly visits, showed some promise in helping children with
autism successfully complete more steps, progress at a quicker rate, and exhibit
lower levels of behavioral distress within a dental appointment, compared to a
traditional tell-show-do approach.
PMID- 27617381
TI - Does Addition of Propolis to Glass Ionomer Cement Alter its Physicomechanical
Properties? An in Vitro Study.
AB - Propolis is a natural resinous substance produced by honey bees. The
antimicrobial effects of glass ionomer cement have been shown to improve with the
addition of propolis; however its effect on the physicomechanical properties of
the cement is not known. AIM: The purpose of this study was to evaluate the
compressive strength and solubility of conventional restorative glass ionomer
cement following the addition of propolis. STUDY DESIGN: Twenty half cylindrical
samples were prepared with conventional restorative glass ionomer cement formed
the control group. Another twenty samples were prepared with propolis added to
conventional restorative glass ionomer cement formed the experimental group. The
compressive strength was assessed using universal testing machine. To assess
solubility, the samples were immersed in deionised water at room temperature, for
7 days. The solubility was measured as a difference in the weight of the sample;
prior to immersion and following immersion at the end of each day. RESULTS: The
control group had a significantly higher mean compressive strength of 146.26 Mpa
as compared to the experimental group (135.06 Mpa). The solubility between the
groups was significant. CONCLUSION: In comparison to the control group,
incorporation of propolis to conventional restorative glass ionomer cement
decreased the compressive strength significantly. The solubility of the cement in
the experimental group increased significantly over 7day period as compared to
the control group.
PMID- 27617382
TI - Comparison of CPP-ACP, Tri-Calcium Phosphate and Hydroxyapatite on
Remineralization of Artificial Caries Like Lesions on Primary Enamel -An in vitro
Study.
AB - OBJECTIVES: To compare CPP-ACP, Tri-calcium phosphate and Hydroxyapatite on
remineralization of artificial caries like lesions on primary enamel. STUDY
DESIGN: Ten extracted Primary molars coated with nail varnish, leaving a window
of 2*4 mm on buccal and lingual surface were immersed in demineralizing solution
for 96 hours and sectioned longitudinally to obtain 40 sections (4 sections per
tooth) and were randomly divided into 4 groups (A to D) n=10; Group A: negative
control, Group B: CPP-ACP, Group C: Tri-calcium phosphate, Group D:
Hydroxyapatite. Sections were subjected to pH cycling for 10 days and were
evaluated by polarized light microscope before and after treatment. RESULTS:
Intra group comparison of demineralization and remineralization was done by
paired t-test. One way ANOVA was used for multiple group comparisons followed by
post HOC TUKEY'S Test for group wise comparisons. Remineralization was found more
with Group D followed by Group B, C and A. CONCLUSION: Hydroxyapatite showed
better remineralization when compared to CPP-ACP and Tri-calcium phosphate.
PMID- 27617383
TI - Presurgical Nasoalveolar Molding Therapy Using Figueroa's NAM Technique in
Unilateral Cleft Lip and Palate Patients: A Preliminary Study.
AB - OBJECTIVE: The objective of the study was to evaluate the results of nasoalveolar
molding (NAM) in the treatment of patients with unilateral cleft lip and palate
using a modified technique in a South Indian population. STUDY DESIGN: The design
was a prospective study with blinded measurements. The sample constituted 10
complete unilateral cleft lip and palate (UCLP) patients who underwent NAM
therapy by the same operator. Direct extra and intra oral anthropometric
measurements were done using a digital vernier caliper before and after NAM
therapy. A photographic evaluation was also done to rate the nasal deformity post
NAM therapy. The differences between measurements were statistically analyzed
using paired t tests. RESULTS: The extra oral measurements revealed a
statistically significant increase in bi-alar width, columellar length and width.
The intraoral measurements demonstrated a statistically significant reduction in
anterior alveolar cleft width. There was also a significant increase in arch
width and greater and lesser segments length. All cases were rated as improved by
the surgeons in photographic analysis. CONCLUSION: The study has quantitatively
shown that the modified NAM therapy improved nasal asymmetry by columellar
lengthening and effectively molded the maxillary alveolar arch.
PMID- 27617384
TI - Oral Health Education in Children before Dental Treatment under General
Anesthesia.
AB - OBJECTIVE: The aim of this study was to evaluate the attitude of parents towards
the oral health of their children before oral rehabilitation under general
anesthesia (GA). STUDY DESIGN: Children receiving dental treatment under GA
between November 2013 and July 2014 in the Pediatric Dentistry Department
(University Hospital Center, Toulouse, France) were enrolled in an oral health
preventive program. An anonymous questionnaire was self-administered by the
parents during the pre-operative session. RESULTS: The sample comprised 67
children with a mean age of 4.8 years. 48 % of the parents had difficulties in
maintaining the oral hygiene of their child. Two thirds of them reported a lack
of cooperation. An adult cleaned the child's teeth in 43% of the cases. 14% of
the study population brushed their teeth twice a day or more. In addition, half
of the parents reported that they modified food consumption or teeth cleaning
habits of their children since the initial consultation. CONCLUSIONS: This study
suggests a low compliance of parents and children with the recommendations on
oral hygiene and food consumption given at the initial visit and demonstrates the
feasibility of a preventive program in this population.
PMID- 27617385
TI - Prevalence of Posterior Crossbite for Orthodontic Treatment Timing.
AB - OBJECTIVE: To evaluate the prevalence and distribution of posterior crossbite in
different dentition stages in a Turkish sample. STUDY DESIGN: 1554 subjects (843
girls, 711 boys) aged 4-25 years were evaluated to determine the prevalence of
posterior crossbite in a Turkish sample. The subjects were classified according
to four dentition stages (primary, early mixed, late mixed and permanent) and
transversal occlusal status. The statistical evaluation was done by Chi-square,
Fischer exact tests. RESULTS: Bilateral and unilateral crossbite on the right and
left sides had the highest frequency in the permanent dentition (51.0%, 47.3%,
and 53.6%; respectively). No significant differences were found between
unilateral (right and left) and bilateral crossbite with regard to dentition
stages. No significant differences were found between unilateral right or left
side posterior crossbite with regard to dentition stages. CONCLUSION: An
increasing trend in the prevalence of posterior crossbite was observed from the
primary dentition towards permanent dentition in this study.
PMID- 27617386
TI - The Inclusion of Nurses in Pharmaceutical Industry-Sponsored Events: Guess Who Is
Also Coming to Dinner?
PMID- 27617387
TI - Cluster Sets: Permitting Greater Mechanical Stress Without Decreasing Relative
Velocity.
AB - PURPOSE: To determine the effects of intraset rest frequency and training load on
muscle time under tension, external work, and external mechanical power output
during back-squat protocols with similar changes in velocity. METHODS: Twelve
strength-trained men (26.0 +/- 4.2 y, 83.1 +/- 8.8 kg, 1.75 +/- 0.06 m, 1.88:0.19
one-repetition-maximum [1RM] body mass) performed 3 sets of 12 back squats using
3 different set structures: traditional sets with 60% 1RM (TS), cluster sets of 4
with 75% 1RM (CS4), and cluster sets of 2 with 80% 1RM (CS2). Repeated-measures
ANOVAs were used to determine differences in peak force (PF), mean force (MF),
peak velocity (PV), mean velocity (MV), peak power (PP), mean power (MP), total
work (TW), total time under tension (TUT), percentage mean velocity loss (%MVL),
and percentage peak velocity loss (%PVL) between protocols. RESULTS: Compared
with TS and CS4, CS2 resulted in greater MF, TW, and TUT in addition to less MV,
PV, and MP. Similarly, CS4 resulted in greater MF, TW, and TUT in addition to
less MV, PV, and MP than TS did. There were no differences between protocols for
%MVL, %PVL, PF, or PP. CONCLUSIONS: These data show that the intraset rest
provided in CS4 and CS2 allowed for greater external loads than with TS,
increasing TW and TUT while resulting in similar PP and %VL. Therefore, cluster
set structures may function as an alternative method to traditional strength- or
hypertrophy-oriented training by increasing training load without increasing %VL
or decreasing PP.
PMID- 27617389
TI - Increases in Circulating Cell-Free DNA During Aerobic Running Depend on Intensity
and Duration.
AB - PURPOSE: Increases in concentrations of circulating cell-free DNA (cfDNA) have
recently been demonstrated to occur in a variety of exhausting and vigorous
exercise settings. Here, the authors assessed the association of cfDNA with
exercise duration and intensity in a controlled test-retest setting of a
regenerative up-to-moderate-level aerobic run. METHODS: In a pretest, the lactate
threshold (LT) was determined in 13 participants (range 10.8-13.4 km/h) by using
a step-wise incremental running test. The speed of the 2 endurance runs was set
to 9.6 km/h for 40 min; for the participants with an LT below the median (12.8
km/h; G1), this was a moderate aerobic run, and for those with an LT above the
median, this was a regenerative run (G2). Capillary cfDNA, lactate, and rating of
perceived exertion (RPE) were assessed before, every 10 min during, and after the
runs. RESULTS: During the last 30 min of the 2 runs, lactate did not increase,
whereas cfDNA increased steadily (3.46-fold for G1 and 2.05-fold for G2).
Intraclass correlation for cfDNA was high (r = .81, P < .0001) for all runners
but higher for male participants (r = .92, P < .0001). The correlations of cfDNA
and lactate with RPEs were r = .58 (P < .0001) and r = .32 (P < .05),
respectively. CONCLUSIONS: Both duration and level of intensity were
significantly associated with accumulation of cfDNA. The correlation with RPE and
the high test-retest reliability suggest that cfDNA might be applicable as a
marker to monitor individual training load for aerobic and intermittent
exercises. Future randomized, controlled, longitudinal training studies will have
to reveal the full potential of cfDNA as an exercise-physiology marker.
PMID- 27617388
TI - Anatomical and procedural determinants of catheter-based renal denervation.
AB - BACKGROUND/PURPOSE: Catheter-based renal sympathetic denervation (RDN) can reduce
blood pressure (BP) and sympathetic activity in certain patients with
uncontrolled hypertension. Less is known about the impact of renal anatomy and
procedural parameters on subsequent BP response. METHODS/MATERIALS: A total of
564 patients with resistant hypertension underwent bilateral RDN in 9 centers in
Europe and Australia using a mono-electrode radiofrequency catheter (Symplicity
Flex, Medtronic). Anatomical criteria such as prevalence of accessory renal
arteries (ARA), presence of renal artery disease (RAD), length, and diameter were
analyzed blinded to patient's characteristics. RESULTS: ARA was present in 171
patients (30%), and RAD was documented in 71 patients (13%). On average 11+/-2.7
complete 120-s ablations were performed, equally distributed on both sides. After
6months, BP was reduced by 19/8mmHg (p<0.001 for both). Change of systolic blood
pressure (SBP) was not related to the presence of ARA (-18 vs. -20mmHg; p=NS) or
RAD (-16 vs. -20mmHg; p=NS). Patients with a bilateral diameter<=4mm had a more
pronounced reduction of SBP compared to patients with a unilateral diameter<=4mm
or a bilateral diameter>4mm (-29 vs. -26 vs. -17mmHg; p<0.001). Neither the
length of the renal artery nor the number of RF ablations influenced BP reduction
after 6months. CONCLUSIONS: The diameter of renal arteries correlated with SBP
change after RDN at 6-month follow-up. Change of SBP was not related to the
lengths of the renal artery, presence of ARA, RAD, or the number of RF ablations
delivered by a mono-electrode catheter.
PMID- 27617390
TI - An in vivo multiplexed small-molecule screening platform.
AB - Phenotype-based small-molecule screening is a powerful method to identify
molecules that regulate cellular functions. However, such screens are generally
performed in vitro under conditions that do not necessarily model complex
physiological conditions or disease states. Here, we use molecular cell barcoding
to enable direct in vivo phenotypic screening of small-molecule libraries. The
multiplexed nature of this approach allows rapid in vivo analysis of hundreds to
thousands of compounds. Using this platform, we screened >700 covalent inhibitors
directed toward hydrolases for their effect on pancreatic cancer metastatic
seeding. We identified multiple hits and confirmed the relevant target of one
compound as the lipase ABHD6. Pharmacological and genetic studies confirmed the
role of this enzyme as a regulator of metastatic fitness. Our results highlight
the applicability of this multiplexed screening platform for investigating
complex processes in vivo.
PMID- 27617392
TI - USE OF AFLIBERCEPT FOR THE MANAGEMENT OF REFRACTORY PSEUDOPHAKIC MACULAR EDEMA IN
IRVINE-GASS SYNDROME AND LITERATURE REVIEW.
AB - BACKGROUND/PURPOSE: To present the patient treated for pseudophakic cystoid
macular edema with intravitreal aflibercept. METHODS: Interventional case report.
CASE: An 83-year-old woman presented with decreased vision 1 month after
uneventful cataract surgery. After failure to respond to posterior subtenons
triamcinolone and three Ranibizumab injections, the patient responded to one
intravitreal aflibercept injection. Recurrence occurred two months later, and
therefore three monthly injections were then given. Again the patient responded
although recurrence occurred two months after treatment. The patient refused
further treatment. CONCLUSION: Intravitreal aflibercept may be effective for the
treatment of pseudophakic cystoid macular edema.
PMID- 27617391
TI - A conditional proteomics approach to identify proteins involved in zinc
homeostasis.
AB - Zinc signaling and dynamics play significant roles in many physiological
responses and diseases. To understand the physiological roles of zinc in detail,
comprehensive identification of proteins under high concentration of mobile zinc
ion is crucial. We developed a 'conditional proteomics' approach to identify
proteins involved in zinc homeostasis based on a chemical proteomic strategy that
utilizes designer zinc-responsive labeling reagents to tag such proteins and
quantitative mass spectrometry for their identification. We used this method to
elucidate zinc dyshomeostasis induced by nitric-oxide-triggered oxidative stress
in glioma cells, and we unveiled dynamic changes of the zinc-related proteomes.
Moreover, we characterized unknown zinc-rich vesicles generated by oxidative
stress as endoplasmic-reticulum- and Golgi-related vesicles.
PMID- 27617393
TI - MACULAR DETACHMENT ASSOCIATED WITH ANOMALOUS OPTIC NERVES AND DURAL ECTASIA IN
49, XXXXY SYNDROME.
AB - PURPOSE: To present a case of a patient with XXXXY syndrome, anomalous optic
nerves, and dural ectasia in conjunction with macular detachment. METHODS: Case
report. RESULTS: A 3-year-old boy with XXXXY chromosomal abnormality presented
with bilateral maculopathy. On evaluation, he was found to have anomalous optic
disks with serous detachment of the left eye. Magnetic resonance imaging of the
brain revealed bilateral optic nerve dural ectasia without evidence of elevated
intracranial pressure. CONCLUSION: XXXXY syndrome, like the related condition of
Klinefelter syndrome, can manifest with ocular abnormalities. In the present
case, the dural ectasia may have facilitated access of cerebrospinal fluid
through anomalous optic nerves, resulting in neurosensory detachment.
PMID- 27617394
TI - OPTIC NERVE MENINGOCELE SIMULATING EXTRAOCULAR EXTENSION OF CHOROIDAL MELANOMA.
AB - PURPOSE: To report a case of optic nerve meningocele simulating massive,
recurrent extraocular extension of choroidal melanoma. METHOD: Case report.
RESULTS: A 53-year-old white man with choroidal melanoma in his left eye of 7.3
mm thickness was treated with plaque radiotherapy and transpupillary
thermotherapy. On 1-year follow-up examination, visual acuity was 20/20 in the
right eye and 20/30 in the left eye. The regressed choroidal melanoma scar in the
left eye measured 1.5 mm in thickness with stable margins. The optic disk was
normal. Ultrasonography demonstrated regressed echogenic choroidal scar, with an
echolucent multilobulated retrobulbar mass, suspicious for extraocular extension.
On magnetic resonance imaging, the retrobulbar mass corresponded to a distended
and kinked optic nerve sheath, filled with extensive subarachnoid fluid and
normal-size optic nerve with apposition against the posterior globe. There was no
extraocular extension of tumor. Similar but less distended right optic nerve
sheath was documented, consistent with optic nerve sheath meningocele in both
eyes. Observation was advised and the findings remained stable. CONCLUSION: Optic
nerve sheath meningocele is a benign dilatation of the optic nerve sheath that
can simulate orbital tumor or extraocular extension of intraocular tumor.
Magnetic resonance imaging can reliably differentiate these conditions.
PMID- 27617396
TI - Palladium-Catalyzed Regioselective C-Benzylation via a Rearrangement Reaction:
Access to Benzyl-Substituted Anilines.
AB - An unprecedented C-benzylation rearrangement reaction, catalyzed by palladium, is
reported. The reaction proceeds by rearrangement leading to the direct synthesis
of para or ortho benzyl-substituted N-methylanilines. The product is obtained in
high regioselectivity, without the need to use a ligand for the catalytic
process.
PMID- 27617395
TI - Relationship between adipokines and lipid profile in postmenopausal women with
different apolipoprotein E genotypes.
AB - The aim of the authors of this study was to clarify the relationships among
apolipoprotein E (ApoE) genotype, blood pressure, lipid profile, serum leptin,
and adiponectin in healthy postmenopausal women. The study was conducted between
March 2011 and December 2012 on 266 participants aged 50-65 years from the
Institute of Rural Health in Lublin, Poland. Results showed that women had four
combinations of genotypes: E2/E3, E3/E3, E3/E4, and E4/E4. Carriers of different
genotypes did not differ in terms of age, body mass index (BMI), blood pressure,
total cholesterol, high-density lipoprotein (HDL) cholesterol, and adiponectin
levels. Mean low-density lipoprotein (LDL) cholesterol levels were higher in
epsilon4 carriers compared to non-carriers. Fasting serum leptin concentrations
were higher in homozygotes E4/E4. Leptin correlated positively with BMI in all
study groups and with LDL in E2/E3, E3/E3, and E3/E4. Adiponectin correlated
negatively with triglycerides in E2/E3, E3/E3, and E3/E4 and positively with HDL
in E2/E3 carriers. Adipokines were not associated with blood pressure. Multiple
regression analyses demonstrated associations among leptin, ApoE E4/E4, BMI, and
LDL, and among adiponectin, BMI, and triglycerides. In healthy postmenopausal
women E4/E4 genotype was associated with lower leptin levels. Homozygosity E4/E4
was associated with a more atherogenic lipid profile and possibly dysregulation
of leptin and adiponectin signaling in lipid metabolism.
PMID- 27617397
TI - Brilliant violet fluorochromes in simultaneous multicolor flow cytometry
fluorescence in situ hybridization measurement of monocyte subsets and telomere
length in heart failure.
AB - Conventional analytical methods to determine telomere length (TL) have been
replaced by more precise and reproducible procedures, such as fluorescence in
situ hybridization coupled with flow cytometry (flow-FISH). However, simultaneous
measurement of TL and cell phenotype remains difficult. Relatively expensive and
time-consuming cell-sorting purification is needed to counteract the loss, due to
stringent FISH conditions, of prehybridization fluorescence by the organic
fluorochromes conventionally used in the phenotyping step. Here, we sought to
assess whether the newly developed Brilliant Violet (BV) dyes are valuable to
specifically and simultaneously assess the distribution and telomere attrition of
monocyte subsets circulating in the blood of a cohort of patients with heart
failure. We performed flow-FISH on blood samples from 28 patients with heart
failure. To differentiate among monocyte subsets, we used BV and conventional
fluorochromes conjugated to antibodies against CD86, CD14, CD16, and CD15. We
simultaneously assessed the TLs of the monocyte subsets with a telomere-specific
peptide nucleic acid probe labeled with fluorescein isothiocyanate. The BV dyes
completely tolerated the harsh conditions required for adequate DNA denaturation
and simultaneously provided accurate identification of monocyte subpopulations
and respective TLs. The presented protocol may be faster and less expensive than
those used currently for purposes such as establishing associations among patient
categories, disease progression, monocyte heterogeneity, and aging in the context
of heart failure.
PMID- 27617398
TI - Sinomenine induces the generation of intestinal Treg cells and attenuates
arthritis via activation of aryl hydrocarbon receptor.
AB - Sinomenine (SIN), an anti-arthritis drug, has previously been proven to exert
immunomodulatory activity in rats by inducing intestinal regulatory T-cells (Treg
cells). Here, we assessed the effect of SIN on the generation and function of
Treg cells in autoimmune arthritis, and the underlying mechanisms in view of aryl
hydrocarbon receptor (AhR). The proportions of Treg cells and IL-17-producing T
cells (Th17 cells) differentiated from naive T-cells were analyzed by flow
cytometric analysis. The AhR agonistic effect of SIN was tested by analyzing the
activation of downstream signaling pathways and target genes. The dependence of
intestinal Treg cell induction and arthritis alleviation by SIN on AhR activation
was confirmed in a mouse collagen-induced arthritis (CIA) model. SIN promoted the
differentiation and function of intestinal Treg cells in vitro. It induced the
expression and activity of AhR target gene, promoted AhR/Hsp90 dissociation and
AhR nuclear translocation, induced XRE reporter activity, and facilitated AhR/XRE
binding in vitro, displaying the potential to be an agonist of AhR. In CIA mice,
SIN induced the generation of intestinal Treg cells, and facilitated the
immunosuppressive function of these Treg cells as shown by an adoptive transfer
test. In addition, the induction of intestinal Treg cells and the anti-arthritic
effect of SIN in CIA mice could be largely diminished by the AhR antagonist
resveratrol. SIN attenuates arthritis by promoting the generation and function of
Treg cells in an AhR-dependent manner.
PMID- 27617400
TI - Ductular reactions in the liver regeneration process with local inflammation
after physical partial hepatectomy.
AB - Partial hepatectomy models in mice have been widely used for liver regeneration
studies. A typical procedure removes ~2/3 of the liver by lobular ligation
without tissue dissection. However, hepatectomy in humans involves physical
damage (ie, physical partial hepatectomy, PPHx). Therefore, the liver
regeneration process after PPHx should involve reactions to acute local injury
followed by systematic remodeling. To clarify the liver regeneration process
after PPHx, we used a murine liver injury model that mimics the actual human
surgical procedure. A 20-30% PPHx was performed by transection of the left lobe
of the liver using an ultrasonically activated scalpel in mice. Gene expression
and morphological characteristics were analyzed during the liver regeneration
process. Liver weight continuously increased by hypertrophic reaction of
hepatocytes, whereas Ki67 staining showed hepatocyte proliferation. At the
transected border, emergence of ductular reactions, a representative process of
hepatic tissue remodeling that contain liver stem/progenitor cells, were
observed. Gene expression of the transected border and non-damaged lobes revealed
that inflammatory cytokine- and extracellular matrix-associated genes were
significantly upregulated at the transected border. Our PPHx model triggered
local extracellular matrix remodeling that resulted in ductular reactions. These
processes occurred during the tissue repair process in local inflammatory
responses as well as compensatory hepatocyte hypertrophy of the entire liver.
These findings may provide insight for elucidating the mechanism of tissue repair
and regeneration of the liver after PPHx.
PMID- 27617401
TI - Protein phosphatase 2A Calpha regulates proliferation, migration, and metastasis
of osteosarcoma cells.
AB - Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein
phosphatase 2A (PP2A) participates in regulating many important physiological
processes, such as cell cycle, growth, apoptosis, and signal transduction. In
this study, we examined the expression and function of PP2A Calpha in
osteosarcoma cells. PP2A Calpha expression was expected to be higher in malignant
osteosarcoma tissues. PP2A Calpha expression level and PP2A activity was higher
in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and
in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A,
reduced cell viability and induced apoptosis in LM8 cells. PP2A Calpha-knockdown
LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial
structures than that in original LM8 cells. Focal adhesion kinase phosphorylation
and NF-kappaB activity decreased in shPP2A-treated cells. Sensitivity to serum
deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a
lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A
Calpha resulted in a decrease in the migration ability of LM8 cells in vitro.
Reduction in PP2A Calpha levels in vivo suppressed proliferation and metastasis
in LM8 cells. PP2A Calpha expression was also higher in human osteosarcoma MG63
and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and
reduction in PP2A Calpha levels suppressed the cell proliferation rate and
migration ability of MG63 cells. These results indicate that PP2A Calpha has a
critical role in the proliferation and metastasis of osteosarcoma cells;
therefore, its inhibition could potentially suppress the malignancy of
osteosarcoma cells.
PMID- 27617399
TI - Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by
suppressing the NF-kappaB signaling pathway.
AB - Endotoxic shock is the primary cause of morbidity and mortality in hospital
patients, creating an urgent need to explore the mechanisms involved in sepsis.
Our previous studies showed that T-cell immunoglobulin- and mucin-domain
containing molecule-4 (Tim-4) attenuated the inflammatory response through
regulating the functions of macrophages. However, the mechanism by which Tim-4
does this has not been fully elucidated. In this study, we found that Tim-4
expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock.
Interestingly, the survival rate of mice in the Tim-4 overexpression group was
higher than that of the control group after LPS administration. To investigate
the function of Tim-4 in LPS-induced inflammation, we further demonstrated that
Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by
macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-kappaB)
signal inhibition showed that Tim-4 inhibited cytokine production via NF-kappaB
signaling pathway. This study indicates that Tim-4 may exert its immune
modulation by regulating inflammatory factor secretion and might act as a novel
potential target for inflammatory diseases, especially endotoxic shock.
PMID- 27617402
TI - Inhibition of Bcl-2 family members sensitizes mesenchymal chondrosarcoma to
conventional chemotherapy: report on a novel mesenchymal chondrosarcoma cell
line.
AB - Mesenchymal chondrosarcomas are rare and highly aggressive sarcomas occurring in
bone and soft tissue, with poor overall survival. Bcl-2 expression was previously
shown to be upregulated in mesenchymal chondrosarcomas. We here report on a newly
derived mesenchymal chondrosarcoma cell line, MCS170, in which we investigated
treatment with the BH3 mimetic ABT-737 alone or in combination with conventional
chemotherapy as a possible new therapeutic strategy. The presence of the
characteristic HEY1-NCOA2 fusion was confirmed in the MCS170 cell line using
FISH, RT-PCR, and sequencing. The MCS170 cell line was treated with ABT-737 alone
or in combination with doxorubicin or cisplatin. Cell viability and proliferation
was determined using WST-1 viability assays and the xCELLigence system.
Expression of Bcl-2 family members was studied using immunohistochemistry.
Apoptosis was determined using the caspase-glo 3/7 assay and western blot for
PARP cleavage. The MCS170 cell line was sensitive to doxorubicin treatment with
an IC50 of 0.09 MUM after 72 h, but more resistant to cisplatin treatment with an
IC50 of 4.5 MUM after 72 h. Cells showed little sensitivity toward ABT-737 with
an IC50 of 1.8 MUM after 72 h. Combination treatments demonstrated ABT-737
synergism with cisplatin as well as doxorubicin as shown by induction of
apoptosis and reduction in cell proliferation. Restoration of the apoptotic
machinery by inhibition of Bcl-2 family members sensitizes MCS170 mesenchymal
chondrosarcoma cells to conventional chemotherapy. This indicates that combining
the inhibition of Bcl-2 family members with conventional chemotherapy can be a
possible therapeutic strategy for patients with mesenchymal chondrosarcoma.
PMID- 27617403
TI - Hepatitis B core antigen upregulates B7-H1 on dendritic cells by activating the
AKT/ERK/P38 pathway: a possible mechanism of hepatitis B virus persistence.
AB - B7-H1 binding to programmed death-1 may deliver a coinhibitory signal to T cells
that is involved in the regulation of T-cell activation and tolerance. B7-H1
plays a key role in dysfunction of dendritic cells (DCs) during chronic HBV
infection, but the expression mechanism of B7-H1 remains unclear. One hundred and
twenty-nine patients with chronic HBV infection were categorized into either the
immune tolerance phase (HBV-IT), the immune clearance phase (HBV-IC), or the
inactive carrier phase (HBV-IA). Twenty healthy volunteers were enrolled as
controls. Another 16 patients with HBeAg-positive chronic Hepatitis B were
enrolled, and entecavir was administrated at 0.5 mg per day for 6 months. The B7
H1 expression level on peripheral DCs was tested by flow cytometry. In vitro,
expression levels of B7-H1 and signaling molecules on monocyte-derived DC (MO-DC)
induced by recombinant hepatitis B virus C antigen (rhHBcAg) were examined by RT
PCR, flow cytometry, and western blotting, and the apoptosis rate was tested by
flow cytometry. The percentages of peripheral DCs and myeloid DCs (mDCs) were
decreased and B7-H1 levels were increased in patients compared with controls.
Serum HBV-DNA levels were positively correlated with B7-H1 levels on mDCs in
patients with HBV-IT. B7-H1 levels on peripheral DCs from patients with chronic
hepatitis B decreased after antiviral therapy. In vitro studies demonstrated that
the B7-H1 level on MO-DC was upregulated by rhHBcAg, which resulted from the
activation of PI3K-AKT, ERK, and P38 signaling pathways, and the percentage of MO
DC was downregulated by rhHBcAg. In addition, rhHBcAg promoted the apoptosis of
MO-DC. The data suggest that HBcAg induced B7-H1 upregulation by activating AKT,
ERK, and P38 signaling pathways, which inhibited the clearance of HBV-DNA and the
reduction of DCs contributed to immune tolerance, which may correlate with
apoptosis.
PMID- 27617405
TI - Innovative Techniques for Maximizing Limb Salvage and Function.
AB - Concurrent injuries to multiple extremities present unique challenges to the
reconstructive surgeon. The primary goal in such scenarios is to optimize
functional outcomes. The goal of this article is to present an overview of
various techniques necessary to provide sufficient soft tissue and preserve
amputation limb lengths and function. The concept of innovative techniques for
maximizing limb savage and function is presented using an index patient with
multiple extremity third- and fourth-degree burn injuries resulting in
nonsalvageable lower extremities and severe left-hand wounds. A review of other
potential innovative techniques is discussed. The burn injury resulted in a need
for bilateral guillotine below-knee amputations. Above-knee amputation was
avoided in the left leg using a parascapular free fasciocutaneous flap, while
through-knee amputation was preferred to above-knee amputation in the right leg.
The preservation of areas with questionable viability resulted in salvaging the
left hand of the patient using digital palmar flaps to resurface the dorsum with
creation of a first web-space. Maintenance of maximal viable length of limbs and
any residual function in the limbs can be of significant functional benefit to
multiple limb amputation patients. Maximizing the limb length in such patients is
critical, and typical "rules" that have traditionally been utilized to minimize
numbers of operations and optimize prosthetic fit may not apply.
PMID- 27617406
TI - Burn Wound Mucormycosis: A Case Study on Poor Wound Healing.
AB - Mucormycosis is a rare, rapidly progressive and often fatal fungal infection. The
rarity of the condition lends itself to unfamiliarity, delayed treatment, and
poor outcomes. Diagnosis of fungal infections early enough to enable appropriate
treatment occurs in less than half of affected patients. A 56-year-old male with
a history of diabetes mellitus II, hepatitis C, and intravenous drug abuse was
involved in a rollover motor vehicle accident. He sustained circumferential
partial and full-thickness burns to his lower extremities with 20% BSA burns. He
ultimately required a below-knee amputation of his right lower extremity due to
poor wound healing and nonviability of the soft tissue and foot. Debridement
found muscle fibers that were necrotic and purulent. Pathology revealed Mucor
species with extensive vascular invasion. This case and discussion highlights the
importance of maintaining vigilance for mycotic infections and acting
appropriately when there are concerning signs and symptoms of serious wound
complications. Caretakers of severe trauma patients should have a high level of
suspicion for complications and be cognizant of the American Burn Association's
guidelines for systemic inflammatory response syndrome and sepsis. Progressive
necrosis outside the confines of the original burn wound should raise concern for
impaired wound healing, an immunocompromised state or an underlying infection.
PMID- 27617404
TI - Immortalization of human normal and NF1 neurofibroma Schwann cells.
AB - Neurofibromas, which are benign Schwann cell tumors, are the hallmark feature in
the autosomal dominant condition neurofibromatosis 1 (NF1) and are associated
with biallelic loss of NF1 gene function. There is a need for effective therapies
for neurofibromas, particularly the larger, plexiform neurofibromas. Tissue
culture is an important tool for research. However, it is difficult to derive
enriched human Schwann cell cultures, and most enter replicative senescence after
6-10 passages, impeding cell-based research in NF1. Through exogenous expression
of human telomerase reverse transcriptase and murine cyclin-dependent kinase
(mCdk4), normal (NF1 wild-type), neurofibroma-derived Schwann cells heterozygous
for NF1 mutation, and neurofibroma-derived Schwann cells homozygous for NF1
mutation were immortalized, including some matched samples from the same NF1
patient. Initial experiments employed retroviral vectors, while subsequent work
utilized lentiviral vectors carrying these genes because of improved efficiency.
Expression of both transgenes was required for immortalization. Molecular and
immunohistochemical analysis indicated that these cell lines are of Schwann cell
lineage and have a range of phenotypes, many of which are consistent with their
primary cultures. This is the first report of immortalization and detailed
characterization of multiple human NF1 normal nerve and neurofibroma-derived
Schwann cell lines, which will be highly useful research tools to study NF1 and
other Schwann tumor biology and conditions.
PMID- 27617407
TI - Risk Factors for Acute Kidney Injury in Patients With Burn Injury: A Meta
Analysis and Systematic Review.
AB - Acute kidney injury (AKI) is a fatal complication of burn injury. Few systematic
reviews to date have focused on the risk factors predisposing to AKI in patients
with burn injury. The aim of this article is to identify the risk factors for the
occurrence of AKI in burn patients, thus providing theoretical evidence for
prevention and treatment. We performed a systematic review and meta-analysis of
studies determining the prevalence, risk factors, and outcomes of AKI in patients
with burn injury. An electronic search (up to April 2016) was performed using
Pubmed, Embase, Web of Knowledge, and the Cochrane Library databases. Finally, a
total of 18 articles (nine prospective cohort, seven retrospective cohort, two
case-control) meeting the eligibility criteria were included. The pooled
incidence of AKI was 39.6% (95% confidence interval = 34.7-44.4%). Significant
risk factors for the occurrence of AKI included age (odds ratio [OR] = 3.78 [1.28
6.27]), TBSA (OR = 15.66 [11.01-20.31]), full-thickness TBSA (OR = 15.66 [11.01
20.31]), flame burn (OR = 1.56 [1.09-2.25]), inhalation injury (OR = 2.97 [1.80
4.89]), abbreviated burn severity index on admission (OR = 2.42 [1.87-2.98]),
sequential organ failure assessment score on admission (OR = 2.69 [1.39-3.98]),
baseline blood urea nitrogen (OR = 2.11 [0.72-3.51]), serum creatinine (OR = 2.69
[1.39-3.98]), and sepsis (OR = 4.42 [1.75-11.18]). In addition, burn patients
with AKI are more likely to have long stay in intensive care unit and high
mortality. AKI is a common complication and occurs at a remarkable rate in burn
patients. We identified 10 variables as independent risk factors for the
development of AKI in burn patients. Our findings may help clinicians to develop
effective preventive and therapeutic strategies and provide appropriate, timely
initial treatment.
PMID- 27617408
TI - ADHD, Methylphenidate, and Childhood Epilepsy.
AB - Investigators from the Department of Functional Neurology, Epileptology and
Epilepsy Institute (IDEE), and the Lyon's University Hospital examined the
clinical determinants of ADHD severity in children with epilepsy (CWE) along with
the response to treatment with methylphenidate (MPH).
PMID- 27617411
TI - Dynamic monitoring of antimicrobial resistance using magnesium zinc oxide
nanostructure-modified quartz crystal microbalance.
AB - Antimicrobial resistance (AMR) is becoming a major global-health concern
prompting an urgent need for highly-sensitive and rapid diagnostic technology.
Traditional assays available for monitoring bacterial cultures are time-consuming
and labor-intensive. We present a magnesium zinc oxide (MZO) nanostructure
modified quartz crystal microbalance (MZOnano-QCM) biosensor to dynamically
monitor antimicrobial effects on E. coli and S. cerevisiae. MZO nanostructures
were grown on the top electrode of a standard QCM using metal-organic chemical
vapor deposition (MOCVD). The MZO nanostructures are chosen for their
multifunctionality, biocompatibility, and giant effective sensing surface. The
MZO surface-wettability and morphology are controlled, offering high-sensitivity
to various biological/biochemical species. MZO-nanostructures showed over 4-times
greater cell viability over ZnO due to MZO releasing 4-times lower Zn2+ density
in the cell medium than ZnO. The MZOnano-QCM was applied to detect the effects of
ampicillin and tetracycline on sensitive and resistant strains of E.coli, as well
as effects of amphotericin-B and miconazole on S. cerevisiae through the device's
time-dependent frequency shift and motional resistance. The MZOnano-QCM showed 4
times more sensitivity over ZnOnano-QCM and over 10-times better than regular
QCM. For comparison, the optical density at 600nm (OD600) method and the cell
viability assay were employed as standard references to verify the detection
results from MZOnano-QCM. In the case of S. cerevisiae, the OD600 method failed
to distinguish between cytotoxic and cytostatic drug effects whereas the MZOnano
QCM was able to accurately detect the drug effects. The MZOnano-QCM biosensor
provides a promising technology enabling dynamic and rapid diagnostics for
antimicrobial drug development and AMR detection.
PMID- 27617409
TI - A randomized, controlled, multicentre clinical trial of post-extraction alveolar
ridge preservation.
AB - AIM: To compare the effectiveness of two-ridge preservation treatments. MATERIALS
AND METHODS: Forty subjects with extraction sockets exhibiting substantial buccal
dehiscences were enrolled and randomized across 10 standardized centres.
Treatments were demineralized allograft plus reconstituted and cross-linked
collagen membrane (DFDBA + RECXC) or deproteinized bovine bone mineral with
collagen plus native, bilayer collagen membrane (DBBMC + NBCM). Socket dimensions
were recorded at baseline and 6 months. Wound closure and soft tissue
inflammation were followed post-operatively, and biopsies were retrieved for
histomorphometric analysis at 6 months. RESULTS: Primary endpoint: at 6 months,
extraction socket horizontal measures were significantly greater for DBBMC + NBCM
(average 1.76 mm greater, p = 0.0256). Secondary and Exploratory endpoints: (1)
lingual and buccal vertical bone changes were not significantly different between
the two treatment modalities, (2) histomorphometric % new bone and % new bone +
graft were not significantly different, but significantly more graft remnants
remained for DBBMC; (3) at 1 month, incision line gaps were significantly greater
and more incision lines remained open for DFDBA + RECXC; (4) higher inflammation
at 1 week tended to correlate with lower ridge preservation results; and (5)
deeper socket morphologies with thinner bony walls correlated with better ridge
preservation. Thirty-seven of 40 sites had sufficient ridge dimension for implant
placement at 6 months; the remainder were DFDBA + RECXC sites. CONCLUSION: DBBMC
+ NBCM provided better soft tissue healing and ridge preservation for implant
placement. Deeper extraction sockets with higher and more intact bony walls
responded more favourably to ridge preservation therapy.
PMID- 27617410
TI - Novel strategy for sulfapyridine detection using a fully integrated
electrochemical Bio-MEMS: Application to honey analysis.
AB - Sulfapyridine (SPy) is a sulfonamide antibiotic largely employed as veterinary
drugs for prophylactic and therapeutic purposes. Therefore, its spread in the
food products has to be restricted. Herein, we report the synthesis and
characterization of a novel electrochemical biosensor based on gold
microelectrodes modified with a new structure of magnetic nanoparticles (MNPs)
coated with poly(pyrrole-co-pyrrole-2-carboxylic acid) (Py/Py-COOH) for high
efficient detection of SPy. This analyte was quantified through a competitive
detection procedure with 5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid-BSA
(SA2-BSA) antigens toward polyclonal antibody (Ab-155). Initially, gold working
electrodes (WEs) of integrated biomicro electro-mechanical system (BioMEMS) were
functionalized by Ppy-COOH/MNPs, using a chronoamperometric (CA)
electrodeposition. Afterward, SA2-BSA was covalently bonded to Py/Py-COOH/MNP
modified gold WEs through amide bonding. The competitive detection of the analyte
was made by a mixture of a fixed concentration of Ab-155 and decreasing
concentrations of SPy from 50ugL-1 to 2ngL-1. Atomic Force Microscopy
characterization was performed in order to ensure Ppy-COOH/MNPs electrodeposition
on the microelectrode surfaces. Electrochemical measurements of SPy detection
were carried out using electrochemical impedance spectroscopy (EIS). This
biosensor was found to be highly sensitive and specific for SPy, with a limit of
detection of 0.4ngL-1. This technique was exploited to detect SPy in honey
samples by using the standard addition method. The measurements were highly
reproducible for detection and interferences namely, sulfadiazine (SDz),
sulfathiazole (STz) and sulfamerazine (SMz). Taking these advantages of
sensitivity, specificity, and low cost, our system provides a new horizon for
development of advanced immunoassays in industrial food control.
PMID- 27617412
TI - Monitoring growth and antibiotic susceptibility of Escherichia coli with
photoluminescence of GaAs/AlGaAs quantum well microstructures.
AB - Development of quick and reliable methods to investigate antibiotic
susceptibility of bacteria is vital to prevent inappropriate and untargeted use
of antibiotics and control the antibiotic resistance crisis. The authors have
developed an innovative, low-cost and rapid approach to evaluate antibiotic
susceptibility of bacteria by employing photoluminescence (PL) emission of
photocorroding GaAs/AlGaAs quantum well (QW) biochips. The biochips were
functionalized with self-assembled monolayers of biotinylated polyethylene glycol
thiols, neutravidin and biotinylated antibodies to immobilize bacteria. The
illumination of a QW biochip with the above bandgap radiation leads to formation
of surface oxides and dissolution of a limited thickness GaAs cap material
(<=10nm) that results in the appearance of a characteristic maximum in the PL
plot collected over time. The position of the PL maximum depends on the
photocorrosion rate which, in turn, depends on the electric charge immobilized on
the surface of the GaAs/AlGaAs biochips. Bacteria captured on the surface of
biochips retard the PL maximum, while growth of these bacteria further delays the
PL maximum. For the bacteria affected by antibiotics a faster occurring PL
maximum, compared with growing bacteria, is observed. By exposing bacteria to
nutrient broth and penicillin or ciprofloxacin, the authors were able to
distinguish in situ antibiotic-sensitive and resistant Escherichia coli bacteria
within less than 3h, considerable more rapid than with culture-based methods. The
PL emission of the heterostructures was monitored with an inexpensive reader.
This rapid determination of bacterial sensitivity to different antibiotics could
have clinical and research applications.
PMID- 27617413
TI - The Cognitive Assessment Interview: A comparative study in first episode and
chronic patients with psychosis.
AB - The Cognitive Assessment Interview (CAI) is an interview-based instrument to
assess cognition considering the impact of cognitive impairment on daily
activities. We aimed to explore the associations of the Spanish version of the
CAI (CAI-Sp) with a neuropsychological battery and a measure of psychosocial
functioning in psychosis. The sample consisted of fifty-six first episode
psychosis (FEP) patients and 66 non-FEP patients, who were assessed with a
neuropsychological battery, the CAI-Sp and the Short Disability Schedule (DAS-S).
Patients also underwent clinical assessment. Additionally, 37 controls were
assessed with the neuropsychological battery and CAI-Sp, for normalization
purposes. The results showed that CAI-Sp scores were overall correlated with the
neuropsychological battery in non-FEP patients. In FEP patients, we found fewer
significant correlations. Most associations were maintained after controlling for
clinical symptoms. CAI-Sp rater scores contributed to the variance in the DAS-S
scores in both groups, as did negative and disorganized symptoms. The CAI-Sp may
be a good instrument to assess cognition in non-FEP patients. In FEP patients, it
was less effective in capturing cognitive impairments and their functional
consequences, probably because cognitive deficits have yet to become evident, due
to the recency of illness onset, and no functional disturbances were observed due
to these cognitive impairments.
PMID- 27617414
TI - Identifying a system of predominant negative symptoms: Network analysis of three
randomized clinical trials.
AB - BACKGROUND: Reasons for the recent mixed success of research into negative
symptoms may be informed by conceptualizing negative symptoms as a system that is
identifiable from network analysis. We aimed to identify: (I) negative symptom
systems; (I) central negative symptoms within each system; and (III) differences
between the systems, based on network analysis of negative symptoms for baseline,
endpoint and change. METHODS: Patients with chronic schizophrenia and predominant
negative symptoms participated in three clinical trials that compared placebo and
amisulpride to 60days (n=487). Networks analyses were computed from the Scale for
the Assessment of Negative Symptoms (SANS) scores for baseline and endpoint for
severity, and estimated change based on mixed models. Central symptoms to each
network were identified. The networks were contrasted for connectivity with
permutation tests. RESULTS: Network analysis showed that the baseline and
endpoint symptom severity systems formed symptom groups of Affect, Poor
responsiveness, Lack of interest, and Apathy-inattentiveness. The baseline and
endpoint networks did not significantly differ in terms of connectivity, but both
significantly (P<0.05) differed to the change network. In the change network the
apathy-inattentiveness symptom group split into three other groups. The most
central symptoms were Decreased Spontaneous Movements at baseline and endpoint,
and Poverty of Speech for estimated change. CONCLUSIONS: Results provide
preliminary evidence for: (I) a replicable negative symptom severity system; and
(II) symptoms with high centrality (e.g., Decreased Spontaneous Movement), that
may be future treatment targets following replication to ensure the curent
results generalize to other samples.
PMID- 27617415
TI - 16q12.2q21: A new susceptibility locus for schizophrenia?
PMID- 27617416
TI - Comparison of the primary cesarean hysterotomy scars after single- and double
layer interrupted closure.
AB - INTRODUCTION: It is unclear whether hysterotomy closure techniques can affect
niche development. Therefore, this study aimed to analyze the effect of single
layer and double-layer interrupted closures of hysterotomy incisions during
primary cesarean section on the formation of uterine niches. MATERIAL AND
METHODS: A prospective cohort study of women undergoing primary cesarean section
was performed between June 2011 and July 2014. Saline contrast sonohysterography
was used to measure the niche depth and residual myometrium. The ratio of the
niche depth to the sum of the niche depth and residual myometrium thickness
(niche ratio) was calculated. RESULTS: Niches were identified in 14/58 (24.1%)
women with single-layer sutures and 55/209 (26.3%) women with double-layer
sutures (p = 0.74). Single-layer closure was associated with more than a five
fold increase in the odds of a niche ratio >=0.4 (odds ratio 5.59; 95% CI 1.71
18.28). CONCLUSION: Single-layer closure may be associated with an increased risk
of larger niches (niche ratio >=0.4), although it may not increase the overall
frequency of niche formation.
PMID- 27617417
TI - parallelnewhybrid: an R package for the parallelization of hybrid detection using
newhybrids.
AB - Hybridization among populations and species is a central theme in many areas of
biology, and the study of hybridization has direct applicability to testing
hypotheses about evolution, speciation and genetic recombination, as well as
having conservation, legal and regulatory implications. Yet, despite being a
topic of considerable interest, the identification of hybrid individuals, and
quantification of the (un)certainty surrounding the identifications, remains
difficult. Unlike other programs that exist to identify hybrids based on
genotypic information, newhybrids is able to assign individuals to specific
hybrid classes (e.g. F1 , F2 ) because it makes use of patterns of gene
inheritance within each locus, rather than just the proportions of gene
inheritance within each individual. For each comparison and set of markers,
multiple independent runs of each data set should be used to develop an estimate
of the hybrid class assignment accuracy. The necessity of analysing multiple
simulated data sets, constructed from large genomewide data sets, presents
significant computational challenges. To address these challenges, we present
parallelnewhybrid, an r package designed to decrease user burden when undertaking
multiple newhybrids analyses. parallelnewhybrid does so by taking advantage of
the parallel computational capabilities inherent in modern computers to
efficiently and automatically execute separate newhybrids runs in parallel. We
show that parallelization of analyses using this package affords users several
fold reductions in time over a traditional serial analysis. parallelnewhybrid
consists of an example data set, a readme and three operating system-specific
functions to execute parallel newhybrids analyses on each of a computer's c
cores. parallelnewhybrid is freely available on the long-term software hosting
site github (www.github.com/bwringe/parallelnewhybrid).
PMID- 27617418
TI - Sudden Death Due to Acute Epiglottitis in Adults: A Retrospective Review of 11
Postmortem Cases.
AB - We report a retrospective review of fatal acute epiglottitis cases in adults in
the province of Ontario, Canada, between 2001 and 2014. Information on
demographics, clinical history, gross, microscopic, and laboratory findings were
collected and analyzed. Eleven cases, predominantly male (73%), with a mean age
of 50 years were identified. Common presenting symptoms included sore throat,
dysphagia, and low-grade fever. The predominant postmortem findings included
hyperemia and edema of the epiglottis and aryepiglottic folds. Histological
features included vascular congestion, stromal edema, and acute inflammation.
Five cases (45%) were positive for growth of various bacterial organisms on blood
and/or tissue cultures. Acute epiglottitis should be in the differential
diagnosis in fatalities presenting with symptoms of upper respiratory tract
infection, followed by an episode of acute shortness of breath. History, thorough
postmortem examination with close attention to the head and neck structures,
histological examination of tissues, and sampling for microbiology will assist in
differentiating epiglottitis from other cases of laryngeal swelling leading to
death.
PMID- 27617419
TI - Cardiac Tumors: Echocardiographic Diagnosis and Forensic Correlations.
AB - In the past, cardiac tumors were a just clinical curiosity and the prognosis was
poor. Surgical management became possible after the advent of cardiopulmonary
bypass, and more recently, preoperative diagnosis was greatly improved by the
development of echocardiography, computed tomography, and magnetic resonance
imaging. The value of echocardiography for diagnosing cardiac mass lesions has
become well established. Numerous advances have occurred in the last 5 decades,
and the evolution of echocardiography involves the development of its many
modalities. This review is intended to help echocardiologists and forensic
pathologists in providing good medical practice when faced with the challenge of
investigating unexpected clinical signs, particularly in young people, or
unexpected postmortem findings.
PMID- 27617420
TI - Pediatric gastrointestinal endoscopy: European Society of Gastrointestinal
Endoscopy (ESGE) and European Society for Paediatric Gastroenterology Hepatology
and Nutrition (ESPGHAN) Guideline Executive summary.
AB - This Executive summary of the Guideline on pediatric gastrointestinal endoscopy
from the European Society of Gastrointestinal Endoscopy (ESGE) and the European
Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) refers
to infants, children, and adolescents aged 0 - 18 years. The areas covered
include: indications for diagnostic and therapeutic esophagogastroduodenoscopy
and ileocolonoscopy; endoscopy for foreign body ingestion; endoscopic management
of corrosive ingestion and stricture/stenosis; upper and lower gastrointestinal
bleeding; endoscopic retrograde cholangiopancreatography, and endoscopic
ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to
inflammatory bowel disease (IBD) have been dealt with in other Guidelines and are
therefore not mentioned in this Guideline. Training and ongoing skill maintenance
will be addressed in an imminent sister publication.
PMID- 27617421
TI - Peroral endoscopic myotomy: a meta-analysis.
AB - Background and study aim: Peroral endoscopic myotomy (POEM) is a relatively novel
minimally invasive technique that is used to treat achalasia and other esophageal
motility disorders. We systematically reviewed the medical literature in order to
evaluate the safety and efficacy of POEM. Methods: We performed a comprehensive
review and meta-analysis of studies published up to March 2016 that reported on
clinical outcomes of POEM. Five databases were searched: MEDLINE, EMBASE, Ovid,
CINAHL, and Cochrane. Results: A total of 36 studies involving 2373 patients were
included in the review. Clinical success (Eckardt score <= 3) was achieved in 98
% (95 % confidence interval [CI] 97 % - 100 %) of patients after the procedure.
The mean Eckardt score decreased from 6.9 +/- 0.15 preoperatively to 0.77 +/-
0.10, 1.0 +/- 0.10, and 1.0 +/- 0.08 within 1, 6, and 12 months of treatment. In
addition, there were significant decreases in the average lower esophageal
sphincter pressure, integrated relaxation pressure, and the average heights of
the barium column following a timed barium esophagogram after the procedure.
After a mean follow-up of 8 months post-procedure, the rates of symptomatic
gastroesophageal reflux, esophagitis on esophagogastroduodenoscopy, and abnormal
acid exposure were 8.5 % (95 %CI 4.9 % - 13 %), 13 % (95 %CI 5.0 % - 23 %), and
47 % (95 %CI 21 % - 74 %), respectively. Conclusions: POEM appears to be safe and
effective based on the large body of current evidence, and warrants consideration
as first-line therapy when an expert operator is available.
PMID- 27617422
TI - Erratum.
PMID- 27617423
TI - Research in Nursing & Health Author Guidelines.
PMID- 27617424
TI - A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small
Cell Lung Cancer.
AB - Drug regulators around the world make decisions about drug approvability based on
qualitative benefit-risk analyses. There is much interest in quantifying
regulatory approaches to benefit and risk. In this work the use of a quantitative
benefit-risk analysis was applied to regulatory decision-making about new drugs
to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks
associated with 20 US Food and Drug Administration (FDA) decisions associated
with a set of candidate treatments submitted between 2003 and 2015 were analyzed.
For benefit analysis, the median overall survival (OS) was used where available.
When not available, OS was estimated based on overall response rate (ORR) or
progression-free survival (PFS). Risks were analyzed based on magnitude (or
severity) of harm and likelihood of occurrence. Additionally, a sensitivity
analysis was explored to demonstrate analysis of systematic uncertainty. FDA
approval decision outcomes considered were found to be consistent with the
benefit-risk logic.
PMID- 27617426
TI - From prompt gamma distribution to dose: a novel approach combining an
evolutionary algorithm and filtering based on Gaussian-powerlaw convolutions.
AB - Range verification and dose monitoring in proton therapy is considered as highly
desirable. Different methods have been developed worldwide, like particle therapy
positron emission tomography (PT-PET) and prompt gamma imaging (PGI). In general,
these methods allow for a verification of the proton range. However,
quantification of the dose from these measurements remains challenging. For the
first time, we present an approach for estimating the dose from prompt gamma-ray
emission profiles. It combines a filtering procedure based on Gaussian-powerlaw
convolution with an evolutionary algorithm. By means of convolving depth dose
profiles with an appropriate filter kernel, prompt gamma-ray depth profiles are
obtained. In order to reverse this step, the evolutionary algorithm is applied.
The feasibility of this approach is demonstrated for a spread-out Bragg-peak in a
water target.
PMID- 27617425
TI - Endovascular Therapy for Acute Ischemic Stroke With Occlusion of the Middle
Cerebral Artery M2 Segment.
AB - Importance: Randomized clinical trials have shown the superiority of endovascular
therapy (EVT) compared with best medical management for acute ischemic strokes
with large vessel occlusion (LVO) in the anterior circulation. However, of 1287
patients enrolled in 5 trials, 94 with isolated second (M2) segment occlusions
were randomized and 51 of these received EVT, thereby limiting evidence for
treating isolated M2 segment occlusions as reflected in American Heart
Association guidelines. Objective: To evaluate EVT safety and effectiveness in M2
occlusions in a cohort of patients with acute ischemic stroke. Design, Setting,
and Participants: This multicenter retrospective cohort study pooled patients
with acute ischemic strokes and LVO isolated to M2 segments from 10 US centers.
Patients with acute ischemic strokes and LVO in M2 segments presenting within 8
hours from their last known normal clinical status (LKN) from January 1, 2012, to
April 30, 2015, were divided based on their treatment into EVT and medical
management groups. Logistic regression was used to compare the 2 groups.
Univariate and multivariate analyses evaluated associations with good outcome in
the EVT group. Main Outcomes and Measures: The primary outcome was the 90-day
modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome);
the secondary outcome was symptomatic intracerebral hemorrhage. Results: A total
of 522 patients (256 men [49%]; 266 women [51%]; mean [SD] age, 68 [14.3] years)
were identified, of whom 288 received EVT and 234 received best medical
management. Patients in the medical management group were older (median
[interquartile range] age, 73 [60-81] vs 68 [56-78] years) and had higher rates
of intravenous tissue plasminogen activator treatment (174 [74.4%] vs 172
[59.7%]); otherwise the 2 groups were balanced. The rate of good outcomes was
higher for EVT (181 [62.8%]) than for medical management (83 [35.4%]). The EVT
group had 3 times the odds of a good outcome as the medical management group
(odds ratio [OR], 3.1; 95% CI, 2.1-4.4; P < .001) even after adjustment for age,
National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program
Early Computed Tomographic Score (ASPECTS), intravenous tissue plasminogen
activator treatment, and time from LKN to arrival in the emergency department
(OR, 3.2; 95% CI, 2-5.2; P < .001). No statistical difference in symptomatic
intracerebral hemorrhage was found (5.6% vs 2.1% for the EVT group vs the medical
management group; P = .10). The treatment effect did not change after adjusting
for center (OR, 3.3; 95% CI, 1.9-5.8; P < .001). Age, NIHSS score, ASPECTS, time
from LKN to reperfusion, and successful reperfusion score of at least 2b (range,
0 [no perfusion] to 3 [full perfusion with filling of all distal branches]) were
independently associated with good outcome of EVT. A linear association was found
between good outcome and time from LKN to reperfusion. Conclusions and Relevance:
Although a randomized clinical trial is needed to confirm these findings,
available data suggest that EVT is reasonable, safe, and effective for LVO of the
M2 segment relative to best medical management.
PMID- 27617427
TI - Reduced germination success of temperate grassland seeds sown in dung:
consequences for post-dispersal seed fate.
AB - Endozoochory is one of the main drivers shaping temperate grassland communities
by maintaining plant populations of its constituents and enabling plants to
colonize new habitats. Successful endozoochorous dispersal implies that seeds not
only get consumed and survive the digestive tract but are also able to develop
into viable seedlings in a dung environment. We experimentally assessed the
germination probability and timing of 15 annual and perennial temperate European
grassland species in cattle and horse dung and in different climatic conditions
(greenhouse and outdoor conditions). Interspecific variation in germinability and
germination timing are found, while life strategy had only an effect on
germination timing. We found adverse effects of both cattle and horse dung on the
germination characteristics of all tested grassland species, but the effects of
cattle dung were more pronounced. In comparison with the control treatment, fewer
seeds emerged in dung and more time was needed to germinate. Also, germination
metrics clearly differed between the artificial greenhouse and outdoor
conditions, with generally a lower germinability in outdoor conditions. According
to our results, a large cost seems to be associated with endozoochorous dispersal
in this stage of the life cycle, as seed dispersal effectiveness strongly depends
on the quality of the deposition site with a lowered survival and germination
probability when seeds are deposited in dung.
PMID- 27617428
TI - Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for
head and neck cancer.
AB - BACKGROUND: The purpose of this study was to analyze the relationship between
pretreatment inflammatory markers and the prognosis of patients with
oropharyngeal, hypopharyngeal, and laryngeal cancers. METHODS: The data for 285
patients treated with curative intent by concurrent chemoradiotherapy (CRT) were
obtained and their pretreatment inflammatory markers, including neutrophil-to
lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to
monocyte ratio (LMR) were calculated. RESULTS: Significant relationships were
observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4,
N2b to N3, and clinical stage III to IV, whereas significant relationships were
observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I
to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR
were all significantly associated with decreases in overall survival (OS) and
disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR
was an independent prognostic factor. CONCLUSION: Pretreatment LMR was found to
be an independent prognostic factor for patients with head and neck cancers
treated by concurrent CRT. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 247
253, 2017.
PMID- 27617429
TI - A minimized human insulin-receptor-binding motif revealed in a Conus geographus
venom insulin.
AB - Insulins in the venom of certain fish-hunting cone snails facilitate prey capture
by rapidly inducing hypoglycemic shock. One such insulin, Conus geographus G1
(Con-Ins G1), is the smallest known insulin found in nature and lacks the C
terminal segment of the B chain that, in human insulin, mediates engagement of
the insulin receptor and assembly of the hormone's hexameric storage form.
Removal of this segment (residues B23-B30) in human insulin results in
substantial loss of receptor affinity. Here, we found that Con-Ins G1 is
monomeric, strongly binds the human insulin receptor and activates receptor
signaling. Con-Ins G1 thus is a naturally occurring B-chain-minimized mimetic of
human insulin. Our crystal structure of Con-Ins G1 reveals a tertiary structure
highly similar to that of human insulin and indicates how Con-Ins G1's lack of an
equivalent to the key receptor-engaging residue PheB24 is mitigated. These
findings may facilitate efforts to design ultrarapid-acting therapeutic insulins.
PMID- 27617432
TI - Between a Rock and a Hard Place: Terminating Cardiopulmonary Resuscitation and
Preserving Opportunities for Organ Donation.
PMID- 27617430
TI - Glycan shield and epitope masking of a coronavirus spike protein observed by cryo
electron microscopy.
AB - The threat of a major coronavirus pandemic urges the development of strategies to
combat these pathogens. Human coronavirus NL63 (HCoV-NL63) is an alpha
coronavirus that can cause severe lower-respiratory-tract infections requiring
hospitalization. We report here the 3.4-A-resolution cryo-EM reconstruction of
the HCoV-NL63 coronavirus spike glycoprotein trimer, which mediates entry into
host cells and is the main target of neutralizing antibodies during infection.
The map resolves the extensive glycan shield obstructing the protein surface and,
in combination with mass spectrometry, provides a structural framework to
understand the accessibility to antibodies. The structure reveals the complete
architecture of the fusion machinery including the triggering loop and the C
terminal domains, which contribute to anchoring the trimer to the viral membrane.
Our data further suggest that HCoV-NL63 and other coronaviruses use molecular
trickery, based on epitope masking with glycans and activating conformational
changes, to evade the immune system of infected hosts.
PMID- 27617431
TI - Natively glycosylated HIV-1 Env structure reveals new mode for antibody
recognition of the CD4-binding site.
AB - HIV-1 vaccine design is informed by structural studies elucidating mechanisms by
which broadly neutralizing antibodies (bNAbs) recognize and/or accommodate N
glycans on the trimeric envelope glycoprotein (Env). Variability in high-mannose
and complex-type Env glycoforms leads to heterogeneity that usually precludes
visualization of the native glycan shield. We present 3.5-A- and 3.9-A-resolution
crystal structures of the HIV-1 Env trimer with fully processed and native
glycosylation, revealing a glycan shield of high-mannose and complex-type N
glycans, which we used to define complete epitopes of two bNAbs. Env trimer was
complexed with 10-1074 (against the V3-loop) and IOMA, a new CD4-binding site
(CD4bs) antibody. Although IOMA derives from VH1-2*02, the germline gene of CD4bs
targeting VRC01-class bNAbs, its light chain lacks the short CDRL3 that defines
VRC01-class bNAbs. Thus IOMA resembles 8ANC131-class/VH1-46-derived CD4bs bNAbs,
which have normal-length CDRL3s. The existence of bNAbs that combine features of
VRC01-class and 8ANC131-class antibodies has implications for immunization
strategies targeting VRC01-like bNAbs.
PMID- 27617433
TI - Effects of Prosthetic Mismatch and Subscapularis Tear on Glenohumeral Contact
Patterns in Total Shoulder Arthroplasty: A Numerical Musculoskeletal Analysis.
AB - Prosthetic components' mismatch and subscapularis (SC) tear are determining
factors for glenoid failure complication in nonconforming total shoulder
arthroplasty (NC-TSA). Risk factors are linked to glenoid prosthetic loading.
However, the mechanisms underlying the clinical observations remain unclear. This
study assessed the combined impact of mismatch and subscapularis tear on glenoid
loading. It was assumed that adequate glenoid loading was associated with
minimal, but non-null, humeral head translations and contact pressure, as well as
with maximal glenoid contact area, and that the center of pressure (COP) on the
glenoid would have a centered displacement pattern. A numerical model was used to
achieve two objectives. The first was to verify whether an optimum mismatch
existed, for which failure risk would be minimal. The second was to explore the
effect of subscapularis tear on the position of applied forces on the glenoid. A
shoulder AnyBody musculoskeletal model was adapted to the arthroplasty context by
introducing humeral head translations and contact between implants. Ten
simulations were computed to compare combinations of varying mismatches (1.4 mm,
3.4 mm, 6.4 mm, 8.6 mm, and 9 mm) with two shoulder conditions (intact-muscle or
subscapularis tear). Humeral head translations, center-of-pressure, contact area,
contact pressure, and glenohumeral joint contact forces were numerically
estimated. Mismatches between 3.4 mm and 6.4 mm were associated with the most
minimal humeral translations and contact pressure, as well as with maximal
contact area. Center of pressure displacement pattern differed according to
shoulder condition, with an outward anterior tendency in presence of tear.
PMID- 27617435
TI - Does Parents' Social Cohesion Influence Their Perception of Neighborhood Safety
and Their Children's Active Commuting to and From School?
AB - BACKGROUND: The role of parents' perceptions of the neighborhood environment in
determining children's active commuting to and from school (ACS) is understudied.
This study examined the association between parents' perceptions of neighborhood
social cohesion, perceived neighborhood safety, and their children's ACS.
METHODS: This cross-sectional analysis (n = 857 from 81 elementary schools in
Texas) examined baseline data from the Texas Childhood Obesity Prevention Policy
Evaluation project. Participants had a mean age of 9.6 (0.6) years, and 50% were
girls. Mixed effects logistic regression models were used to assess gender
stratified associations between parent's perceived social cohesion and children's
ACS and their perception of neighborhood safety. RESULTS: A positive significant
association was observed between levels of perceived social cohesion and
children's ACS for boys (P = 0.047); however, an inverse significant association
was observed among girls (P = 0.033). Parents of boys living in neighborhoods
with medium to high social cohesion were more likely to perceive their
neighborhood as safe compared with parents living in neighborhoods with low
social cohesion, though nonsignificant. Perceived neighborhood safety for walking
and biking was associated with greater ACS among boys (P = 0.003). CONCLUSIONS:
Our study findings indicate that both social and physical environments are
important factors in determining ACS among boys.
PMID- 27617437
TI - Tissues Derived From Reprogrammed Wharton's Jelly Stem Cells of the Umbilical
Cord Provide an Ideal Platform to Study the Effects of Glucose, Zika Virus, and
Other Agents on the Fetus.
AB - The infants of mothers with gestational diabetes mellitus (GDM) have an increased
risk of metabolic and cardiovascular disease. It has been difficult to study the
direct effects of maternal hyperglycemia on the fetus because of inaccessibility
of fetal tissues. The development of tissues that simulate the function of fetal
organs using stem cell technology provides an unprecedented opportunity to study
this disorder. Stem cells in the Wharton's jelly of the umbilical cord (hWJSCs),
possess unique properties that are different from other stem cells. They are
primitive, present in large numbers, non-tumorigenic, hypoimmunogenic,
tumoricidal, and carry a genetic signature that represents the fetus. They are
multipotent but their differentiation into functional pancreatic and
cardiovascular tissues has been challenging. We have been able to reprogram
hWJSCs from normal and GDM cords into induced pluripotent stem cells (iPSCs) from
which a variety of functional fetal tissues including insulin-producing and
cardiovascular tissues could be derived. Such tissues from reprogrammed hWJSCs of
normal and GDM cords that physiologically and genetically mimic the fetus of the
diabetic or non-diabetic mother are an ideal platform to study the effects of
glucose, the Zika virus, and other harmful agents on the fetus. The immature
stemness phenotype of hWJSCs, easy accessibility, availability in large numbers
without the need for propagation, and lower risk of accumulation of epigenetic
mutations make them the most attractive candidate over other umbilical cord cell
types for reprogramming. Additionally, some of their beneficial genes may be
retained in memory in the iPSCs derived from them. J. Cell. Biochem. 118: 437
441, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27617439
TI - Litter Decomposition in a Semiarid Dune Grassland: Neutral Effect of Water Supply
and Inhibitory Effect of Nitrogen Addition.
AB - BACKGROUND: The decomposition of plant material in arid ecosystems is considered
to be substantially controlled by water and N availability. The responses of
litter decomposition to external N and water, however, remain controversial, and
the interactive effects of supplementary N and water also have been largely
unexamined. METHODOLOGY/PRINCIPAL FINDINGS: A 3.5-year field experiment with
supplementary nitrogen and water was conducted to assess the effects of N and
water addition on mass loss and nitrogen release in leaves and fine roots of
three dominant plant species (i.e., Artemisia halondendron, Setaria viridis, and
Phragmites australis) with contrasting substrate chemistry (e.g. N concentration,
lignin content in this study) in a desertified dune grassland of Inner Mongolia,
China. The treatments included N addition, water addition, combination of N and
water, and an untreated control. The decomposition rate in both leaves and roots
was related to the initial litter N and lignin concentrations of the three
species. However, litter quality did not explain the slower mass loss in roots
than in leaves in the present study, and thus warrant further research. Nitrogen
addition, either alone or in combination with water, significantly inhibited dry
mass loss and N release in the leaves and roots of the three species, whereas
water input had little effect on the decomposition of leaf litter and fine roots,
suggesting that there was no interactive effect of supplementary N and water on
litter decomposition in this system. Furthermore, our results clearly indicate
that the inhibitory effects of external N on dry mass loss and nitrogen release
are relatively strong in high-lignin litter compared with low-lignin litter.
CONCLUSION/SIGNIFICANCE: These findings suggest that increasing precipitation
hardly facilitates ecosystem carbon turnover but atmospheric N deposition can
enhance carbon sequestration and nitrogen retention in desertified dune
grasslands of northern China. Additionally, litter quality of plant species
should be considered when modelling the carbon cycle and nutrient dynamics of
this system.
PMID- 27617438
TI - Angiopoetin-2 Signals Do Not Mediate the Hypervascularization of Islets in Type 2
Diabetes.
AB - AIMS: Changes in the islet vasculature have been implicated in the regulation of
beta-cell survival and function during the progression to type 2 diabetes (T2D).
Failure of the beta-cell to compensate for the increased insulin demand in
obesity eventually leads to diabetes; as a result of the complex interplay of
genetic and environmental factors (e.g. ongoing inflammation within the islets)
and impaired vascular function. The Angiopoietin/Tie (Ang/Tie) angiogenic system
maintains vasculature and is closely related to organ inflammation and
angiogenesis. In this study we aimed to identify whether the vessel area within
the islets changes in diabetes and whether such changes would be triggered by the
Tie-antagonist Ang-2. METHODS: Immunohistochemical and qPCR analyses to follow
islet vascularization and Ang/Tie levels were performed in human pancreatic
autopsies and isolated human and mouse islets. The effect of Ang-2 was assessed
in beta-cell-specific Ang-2 overexpressing mice during high fat diet (HFD)
feeding. RESULTS: Islet vessel area was increased in autopsy pancreases from
patients with T2D. The vessel markers Tie-1, Tie-2 and CD31 were upregulated in
mouse islets upon HFD feeding from 8 to 24 weeks. Ang-2 was transiently
upregulated in mouse islets at 8 weeks of HFD and under glucolipotoxic conditions
(22.2 mM glucose/ 0.5 mM palmitate) in vitro in human and mouse islets, in
contrast to its downregulation by cytokines (IL-1beta, IFN-gamma and TNF-alpha).
Ang-1 on the other hand was oppositely regulated, with a significant loss under
glucolipotoxic condition, a trend to reduce in islets from patients with T2D and
an upregulation by cytokines. Modulation of such changes in Ang-2 by its
overexpression or the inhibition of its receptor Tie-2 impaired beta-cell
function at basal conditions but protected islets from cytokine induced
apoptosis. In vivo, beta-cell-specific Ang-2 overexpression in mice induced
hypervascularization under normal diet but contrastingly led to hypovascularized
islets in response to HFD together with increased apoptosis and reduced beta-cell
mass. CONCLUSIONS: Islet hypervascularization occurs in T2D. A balanced
expression of the Ang1/Ang2 system is important for islet physiology. Ang-2
prevents beta-cell mass and islet vascular adaptation in response to HFD feeding
with no major influence on glucose homeostasis.
PMID- 27617440
TI - Two Cases of True Uterine Artery Aneurysms Diagnosed during Pregnancy.
AB - We report 2 cases of true uterine artery aneurysms diagnosed during pregnancy.
Both cases presented with nonspecific symptoms such as urethral obstruction,
minimal vaginal bleeding and lower abdominal pain in the 2nd trimester. Both
aneurysms were diagnosed by color Doppler ultrasound. In the first case labor was
induced at 37 + 4 weeks of gestation. However, due to sudden fetal distress and
maternal abdominal pain, an emergency Caesarean section was performed during
labor, and 3 liters of intra-peritoneal blood were encountered upon laparotomy,
secondary to a ruptured uterine artery aneurysm. In the second case, an elective
Caesarean section was scheduled at 38 + 3 weeks of gestation, and the delivery
and postpartum period were uncomplicated. Albeit a rare condition, a uterine
artery aneurysm should be among the differential diagnosis considered in pregnant
women who present with pelvic and vaginal masses, vague bladder symptoms or
radiating pelvic pain. The diagnosis is readily made by color Doppler imaging.
Elective Caesarean section should be the preferred mode of delivery to avoid
rupture of the aneurysm during labor.
PMID- 27617441
TI - Selective Photocatalytic Disinfection by Coupling StrepMiniSog to the Antibody
Catalyzed Water Oxidation Pathway.
AB - For several decades reactive oxygen species have been applied to water quality
engineering and efficient disinfection strategies; however, these methods are
limited by disinfection byproduct and catalyst-derived toxicity concerns which
could be improved by selectively targeting contaminants of interest. Here we
present a targeted photocatalytic system based on the fusion protein StrepMiniSOG
that uses light within the visible spectrum to produce reactive oxygen species at
a greater efficiency than current photosensitizers, allowing for shorter
irradiation times from a fully biodegradable photocatalyst. The StrepMiniSOG
photodisinfection system is unable to cross cell membranes and like other
consumed proteins, can be degraded by endogenous digestive enzymes in the human
gut, thereby reducing the consumption risks typically associated with other
disinfection agents. We demonstrate specific, multi-log removal of Listeria
monocytogenes from a mixed population of bacteria, establishing the StrepMiniSOG
disinfection system as a valuable tool for targeted pathogen removal, while
maintaining existing microbial biodiversity.
PMID- 27617442
TI - Odorant Responses and Courtship Behaviors Influenced by at4 Neurons in
Drosophila.
AB - In insects, pheromones function as triggers to elicit complex behavior programs,
such as courtship and mating behavior. In most species, the neurons tuned to
pheromones are localized in a specific subset of olfactory sensilla located on
the antenna called trichoid sensilla. In Drosophila there are two classes of
trichoid sensilla, at1 sensilla that contain the dendrites of a single neuron
that is specifically tuned to the male-specific pheromone 11-cis vaccenyl acetate
(cVA), and at4 sensilla that contain three neurons with relatively poorly defined
chemical specificity and function. Using a combination of odorant receptor mutant
analysis, single sensillum electrophysiology and optogenetics, we have examined
the chemical tuning and behavioral consequences of the three at4 olfactory neuron
classes. Our results indicate that one class, Or65abc neurons, are unresponsive
to cVA pheromone, and function to inhibit courtship behaviors in response to an
unknown ligand, while the other two neuron classes, Or88a and Or47b neurons, are
sensitive to a diverse array of fly and non-fly odors, and activation of these
neurons has little direct impact on courtship behaviors.
PMID- 27617444
TI - The Computational Properties of a Simplified Cortical Column Model.
AB - The mammalian neocortex has a repetitious, laminar structure and performs
functions integral to higher cognitive processes, including sensory perception,
memory, and coordinated motor output. What computations does this circuitry
subserve that link these unique structural elements to their function? Potjans
and Diesmann (2014) parameterized a four-layer, two cell type (i.e. excitatory
and inhibitory) model of a cortical column with homogeneous populations and cell
type dependent connection probabilities. We implement a version of their model
using a displacement integro-partial differential equation (DiPDE) population
density model. This approach, exact in the limit of large homogeneous
populations, provides a fast numerical method to solve equations describing the
full probability density distribution of neuronal membrane potentials. It lends
itself to quickly analyzing the mean response properties of population-scale
firing rate dynamics. We use this strategy to examine the input-output
relationship of the Potjans and Diesmann cortical column model to understand its
computational properties. When inputs are constrained to jointly and equally
target excitatory and inhibitory neurons, we find a large linear regime where the
effect of a multi-layer input signal can be reduced to a linear combination of
component signals. One of these, a simple subtractive operation, can act as an
error signal passed between hierarchical processing stages.
PMID- 27617454
TI - Speckle-variance optical coherence tomography: a novel approach to skin cancer
characterization using vascular patterns.
AB - Non-invasive imaging devices are currently being utilized in research and
clinical settings to help visualize, characterize, anddiagnose cancers of the
skin. Speckle-variance optical coherence tomography (svOCT) is one such
technology that offers considerable promise for non-invasive, real time detection
of skin cancers given its added ability to show changes in microvasculature. We
present four early lesions of the face namely sebaceous hyperplasia, basal cell
skin cancer, pigmented actinic keratosis, and malignant melanoma in situ that
each display different important identification markers on svOCT. Up until now,
svOCT has mainly been evaluated for lesion diagnosis using transversal (vertical)
sections. Our preliminary svOCT findings use dynamic en face (horizontal)
visualization to differentiate lesions based on their specific vascular
organizations. These observed patterns further elucidate the potential of this
imaging device to become a powerful tool in patient disease assessment.
PMID- 27617447
TI - IL-25 Promotes Th2 Immunity Responses in Asthmatic Mice via Nuocytes Activation.
AB - BACKGROUND: Interleukin-25 (IL-25) is a potent activator of type-2 immune
responses, and is responsible for airway inflammation in asthma. Previous reports
have shown that IL-25 expressed hyper-reactivity in an experimental mouse-model
of asthma. In addition, the production of IL-13/IL-5 promoted by nuocytes induced
airway inflammation. Thus, it has been questioned whether blocking IL-25 against
its receptor IL-17BR could inhibit the expression of IL-13 and IL-5 via nuocytes,
and further protect against inflammation in ovalbumin (OVA) induced mouse-model
of asthma. METHODS: In this study, in order to investigate the correlation among
IL-25, IL-5, IL-13 and nuocyte activities, we used OVA-sensitization and
challenging to induce the mouse model of asthma. The murine asthmatic model was
validated by histology. The expressions of IL-5, IL-13 and IL-25 were detected by
ELISA, quantitative real-time PCR, and western blotting of the lung tissue.
Nuocyte activation was identified by the levels of ICOS (clone C398.4A) and
T1/ST2 (cloneDJ8) (acting as nuocytes surface markers) in the bronchoalveolar
lavage fluid (BALF). This, in turn, was done by means of flow cytometry. The
expressions of IL-25, IL-5 and IL-13 in our murine model were detected in the
BALF. RESULTS: The mice sensitized and challenged with OVA showed a high
expression of IL-25 in both the mRNA and protein levels in lungs. The expressions
of ICOS and T1/ST2 in BALF were increased. A significant correlation between IL
25 mRNA, protein, and other Th2-cell producing cytokines (such as IL-5 and IL-13)
moreover were identified. Furthermore, when the asthmatic mice were treated with
anti-IL-25, both the inflammatory cells' infiltration and the inflammatory
cytokines' secretion were significantly decreased. The present findings indicate
that IL-25 might be involved in a series of asthmatic immune responses, playing
an important role in the increase of nuocytes, and that its activation is
necessary in maintaining Th2 central memory and sustaining asthmatic
inflammation. CONCLUSION: This study showed that IL-25 promoted the accumulation
of ICOS and T1/ST2 on nuocytes, further induced the pro-inflammatory Th2 cells,
and promoted Th2 cytokine responses in OVA-induced airway inflammation.
PMID- 27617455
TI - A gender-based comparison of promotion and research productivity in academic
dermatology.
AB - PURPOSE: Gender disparities within academic promotion have been reported in
several medical specialties. Female representationin association with research
productivity has not been reported among academic dermatologists. As research
productivity is a heavily weighted factor in determining promotion, we sought to
determine whether gender disparities in academic rank and scholarly impact,
measured by the h-index, exist in academic dermatology. METHODS: In 2015, the
authors determined gender and academic rank using academic dermatology department
websites. H- index and publication range were determined using the Scopus
database. Rank, h-index, and publication range were compared between male and
female academic dermatologists. RESULTS: The h-index of academic dermatologists
increased with successive academic rank from Assistant Professor through
Professor (p<0.001), although no significant difference existed between Chairs
and Professors. Publication range also increased with each successive rank from
Assistant Professor through Professor (p<0.001), with no statistical significant
difference between publication range of Chairs and Professors. Overall, men had
higher h-indices than female colleagues (p<0.001). This difference was maintained
when controlling for academic rank among Assistant Professors, Professors, and
Chairs and when controlling for publication range in years. CONCLUSION: Women in
academic dermatology are underrepresented among senior academic ranks. The
difference in scholarly productivity between male and female academic
dermatologists may contribute to this disparity. Recommendation for
earlyinvolvement in research activities may help minimize this gap.
PMID- 27617456
TI - Congenital cutaneous Langerhans cell histiocytosis and cutaneous mastocytoma in a
child.
AB - Langerhans cell histiocytosis and mastocytoma are clonal disorders of bone-marrow
derived cells, most commonly seen in the pediatric age. Infiltration of mast
cells and Langerhans cells in the same lesion has been published before, but, to
our knowledge, this is the first time that the occurrence of two mastocytomas and
Langerhans cell histiocytosis is reported. It could be hypothesized that both
clonal disorders of bone-marrow-derived cells could have a common origin.
PMID- 27617450
TI - West Nile Virus Spreads Transsynaptically within the Pathways of Motor Control:
Anatomical and Ultrastructural Mapping of Neuronal Virus Infection in the Primate
Central Nervous System.
AB - BACKGROUND: During recent West Nile virus (WNV) outbreaks in the US, half of the
reported cases were classified as neuroinvasive disease. WNV neuroinvasion is
proposed to follow two major routes: hematogenous and/or axonal transport along
the peripheral nerves. How virus spreads once within the central nervous system
(CNS) remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using
immunohistochemistry, we examined the expression of viral antigens in the CNS of
rhesus monkeys that were intrathalamically inoculated with a wild-type WNV. The
localization of WNV within the CNS was mapped to specific neuronal groups and
anatomical structures. The neurological functions related to structures
containing WNV-labeled neurons were reviewed and summarized. Intraneuronal
localization of WNV was investigated by electron microscopy. The known anatomical
connectivity of WNV-labeled neurons was used to reconstruct the directionality of
WNV spread within the CNS using a connectogram design. Anatomical mapping
revealed that all structures identified as containing WNV-labeled neurons
belonged to the pathways of motor control. Ultrastructurally, virions were found
predominantly within vesicular structures (including autophagosomes) in close
vicinity to the axodendritic synapses, either at pre- or post-synaptic positions
(axonal terminals and dendritic spines, respectively), strongly indicating
transsynaptic spread of the virus between connected neurons. Neuronal
connectivity-based reconstruction of the directionality of transsynaptic virus
spread suggests that, within the CNS, WNV can utilize both anterograde and
retrograde axonal transport to infect connected neurons.
CONCLUSIONS/SIGNIFICANCE: This study offers a new insight into the
neuropathogenesis of WNV infection in a primate model that closely mimics WNV
encephalomyelitis in humans. We show that within the primate CNS, WNV primarily
infects the anatomical structures and pathways responsible for the control of
movement. Our findings also suggest that WNV most likely propagates within the
CNS transsynaptically, by both, anterograde and retrograde axonal transport.
PMID- 27617457
TI - Vancomycin-induced linear IgA bullous dermatosis: associations.
AB - Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease.
LABD is considered mostly idiopathic, butsome cases have been reported to be drug
induced, mainly associated with vancomycin (VCM).We present two cases of LABD
possibly associated with VCM used for cardiac surgery prophylaxis; in the
presented cases, the eruptions occurred only after VCM withdrawal, therefore
leaving a question about the relationship between VCM and LABD in these cases.We
reviewed previous reports of VCM-induced LABD and analyzed the following
parameters: gender, age, recent medical history, concurrent medication, latency
period, progression after withdrawal, time to resolution, treatment, and
rechallenge. RESULTS: The causal relationship between VCM and LABD was often
unclear; patients frequently had concurrent medication and symptoms frequently
began and/or progressed after VCM withdrawal. Among the 46 reviewed patients in
addition to our two cases (n=48), 20 (42%) had recent history of cardiac
procedure, cardiac infection, congestive heart failure, or aortic aneurism.
CONCLUSION: Further investigation is needed to ascertain the association between
LABD, VCM, and heart disease.
PMID- 27617458
TI - Phototherapy for the treatment of prurigo nodularis: a review.
AB - BACKGROUND/PURPOSE: Review the available literature on phototherapy for treatment
of prurigo nodularis (PN). METHODS: Literature search was conducted on MEDLINE.
RESULTS: 6 prospective trials, 2 retrospective studies, and 3 case series were
found investigating efficacy and safety of phototherapy for treatment of PN.
CONCLUSION: Although large randomized clinical trials are necessary, phototherapy
appears to be a safe and efficacious treatment for PN, alone and in combination
with other common treatment modalities for PN.
PMID- 27617459
TI - Primary cutaneous angioplasmocellular hyperplasia.
AB - Angioplasmocellular hyperplasia is a rare clinical condition with blood vessel
proliferation and a reactive plasma cell infiltrate. To the best of our knowledge
fewer than 20 cases of cutaneous angioplasmocellular hyperplasia have been
published in English literature. We report a case of a 65-year-old man who
presented with a long standing asymptomatic flesh colored ulcerated nodule on the
back. Histopathological examination revealed a dermal vascular proliferation with
polyclonal plasma cell infiltration. A diagnosis of angioplasmocellular
hyperplasia was established. This entity is rare and we would like to emphasize
the importance of clinico-pathological correlation to differentiate it from
various other conditions of cutaneous plasma cell infiltration.
PMID- 27617461
TI - Leser-Trelat Sign in Tumor-Stage Mycosis Fungoides.
AB - A 71-year-old man presented with numerous pruritic seborrheic keratoses, with an
eruptive onset over the course of 3 months. At presentation, he was also found to
have hypopigmented tumors diffusely scattered throughout his body that were found
to be mycosis fungoides on histologic examination. A theory regarding the
pathophysiology of the development of eruptive seborrheic keratoses in the
presence of mycosis fungoides is briefly discussed and 10 previous case reports
of the Leser-Trelat sign in the setting of mycosis fungoides are reviewed.
PMID- 27617460
TI - Bullous impetigo and pregnancy: Case report and review of blistering conditions
in pregnancy.
AB - BACKGROUND: Bullous impetigo results from Staphylococcus aureus (S. aureus)
release of exfoliative toxins type A and type B thatresults in flaccid, easily
ruptured, bullae in the upper layers of the epidermis. Physiologic, gestation
associated, and incidental skin changes can occur in pregnancy. Blisters in
pregnant women can occur secondary to either common skin disorders orspecific
dermatoses of pregnancy. PURPOSE: To describe a pregnant woman with bullous
impetigo and review bullous conditions in pregnant women. METHODS: PubMed was
used to search the following terms, separately and in combination: blister,
blistering, bullous, gestationis, herpes, herpetiformis, impetigo, pemphigoid,
pregnancy, pregnant, psoriasis, pustular, virus. All papers were reviewed and
relevant manuscripts, along with their reference citations, were evaluated.
RESULTS: Flaccid, easily rupturing, pustules, which developed into superficial
annular erosions with peripheral scale and central healing appeared in a woman of
7-weeks gestation and allergy to penicillin on her lower abdomen, suprapubic
region, perineum, buttocks, and proximal legs. A bacterial culture subsequently
isolated methicillin-susceptible S. aureus. All of the lesions resolved after
treatment with clindamycin. CONCLUSIONS: Bullous impetigo should be considered
in the differential diagnosis of common skin diseases presenting as blistersin
pregnant women.
PMID- 27617462
TI - Treatment of refractory pyoderma gangrenosum with infliximab in a 17-month-old
boy.
AB - This report details the case of a 17-month old boy with refractory multifocal
pyoderma gangrenosum responsive to anti-TNF therapy.
PMID- 27617463
TI - Granuloma inguinale in a 51-year-old man.
AB - Granuloma inguinale, or Donovanosis, is a rare, sexually transmitted ulcerative
disease primarily affecting the genital area. In this report, we present a case
of a 50-year-old man that was diagnosed with granuloma inguinale after a 2-month
history of a penile ulcer. Histological analysis demonstrated the presence of
Donovan bodies within macrophages, confirming the diagnosis. He was subsequently
treated with trimethoprim/sulfamethoxazole with improvement in the ulcer. This
case serves as a reminder to clinicians that although granuloma inguinale is
rarely encountered in the US, it should still be suspected in patients with non
healing penile ulcers.
PMID- 27617464
TI - Papular angiolymphoid hyperplasia and lymphoplasmacytic plaque: a clinical and
histological spectrum.
AB - Acral pseudolymphomatous angiokeratoma of children (APACHE) is a rare form of
cutaneous pseudolymphoma characterized byangiomatous papules with a predilection
for the acral regions of children. Classically, a dense dermal lymphocytic
infiltrate composed of both T and B cells is seen in histological specimens,
together with prominent vessels lined by plump endothelial cells. Increasing
evidence suggests that this condition is neither necessarily acral,
pseudolymphomatous, nor angiokeratomatous. It may not always be a pediatric
disease. Therefore, the correctness of its nomenclature has been questioned.
Herein, we report threecases whose clinical and histological features were
consistent with the diagnosis of APACHE. To our knowledge, this is the first
report of APACHE from Southeast Asia. We also discuss why we believe "APACHE" to
be a misnomer and support "papular angiolymphoid hyperplasia" as a more accurate
and encompassing term. In addition, we illustrate a case with significant
overlapping features with lymphoplasmacytic plaque in children, suggesting that
both entities may exist on a clinical andhistological spectrum.
PMID- 27617465
TI - Infantile epidermolytic ichthyosis with prominent maternal palmoplantar
keratoderma.
AB - Epidermolytic Ichthyosis (EI) is a rare autosomal dominant genodermatosis.
Although an inherited disorder, 50% of cases represent novel mutations. This
disorder presents as a bullous disease in newborns progressing to a lifelong
ichthyotic skin disorder. Other manifestations include palmoplantar keratoderma
(PPK). EI results from mutations in the keratin 1 and keratin 10 genes.
Phenotypic variability is seen in affected individuals based on the genotypic
mutation. We present a mother and her newborn son with EI and prominent PPK in
the mother, which also developed in the child at a few months of age. Genotype
analysis was performed on the newborn child who was found to harbor a mutation in
the keratin 1 gene. This family demonstrates the phenotypic expression of PPK
associated with keratin 1 gene mutations and illustrates the importance of
genotype-phenotypecorrelation in this disorder.
PMID- 27617466
TI - Familial benign pemphigus atypical localization.
AB - We present an atypical case of familial benign pemphigus (Hailey-Hailey disease),
which presented as crusted, annular plaques limited to the back without
intertriginous involvement. We could not find in the literature another patient
with plaques located solely on the back without a prior history of classical
disease.
PMID- 27617467
TI - Idiopathic eruptive macular pigmentation with papillomatosis (IEMPP): A
controversial entity.
AB - A 19-year-old man with a 6-month history of progressive development of
hyperpigmented, velvety plaques on the face and body. A diagnosis of idiopathic
eruptive macular pigmentation with papillomatosis (IEMPP) was determined. This
entity is discussed.
PMID- 27617468
TI - Resident perspectives on a dermatology Quality Improvement curriculum: the
University of Colorado experience.
AB - The Centers for Medicare and Medicaid Services (CMS) have prioritized the
objective of optimizing quality healthcare though quality improvement
initiatives, yet research on dermatology-specific QI programs and their
perceptions among dermatology residents remains limited. We explore residents'
opinions of a dermatology-specific QI scholarly project curriculum implemented at
University of Colorado Denver (UCD) in 2010 and also evaluate residents'
attitudes regarding the value of this curriculum in aiding them to meet ACGME
core competencies.
PMID- 27617469
TI - Angiomatosis dermica difusa de la mama: aportacion de un nuevo caso en paciente
no fumadora.
AB - Diffuse cutaneous angiomatosis is one of the reactive angiomatoses. Historically,
it is associated with lesions located in the lower extremities. Breast
localization is uncommon, but may be under-reported. We report a non-smoking
woman who exhibited this vascular condition of both breasts.
PMID- 27617470
TI - Diclofenac sodium 3% gel for darier's disease treatment.
AB - BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder which
causative gene, ATP2A2, is located atchromosome 12q23-24. The lesions of DD are
skin-coloured to brown, hyperkeratotic, greasy papules that coalesce into warty
plaques commonly involving the seborrhoeic areas of the trunk and face,
especially the scalp margins, temples, ears, and scalp. The most common complaint
associated with the disease is itching, with exacerbations attributed to heat,
sweating, sunlight, lithium, steroid therapy, stress, and menstruation
OBJECTIVES: We report a patient with DD treated with topical diclofenac sodium
3%. METHODS: We report a 33-year-old patient with Darier's Disease. He was
followed in our department since 2009, and we had tried to control several flares
of lesions during follow-up, but oral isotretinoin was not tolerated because of
adverse effects; and oral doxycycline showed lack of efficacy.At April 2014,
patient presented with new lesions, involving anterior chest wall, abdomen, back
and shoulders areas. We started with diclofenac sodium 3% in hyaluronic acid 2.5%
once daily, only applied at abdomen and anterior chest wall. RESULTS: After six
month therapy, hyperkeratotic papules were flattened and less harshness of them
was noticed, even some of them disappeared. CONCLUSIONS: We consider topical
diclofenac therapy as a useful alternative treatment for DD patients, in which
previous therapies have not shown efficacy. We did not observed topical adverse
effects, neither systemic absorption symptoms, but werecognized further and
larger studies are needed to asses the efficacy and safety of this treatment in
DD.
PMID- 27617471
TI - Fixed drug eruption related to fluconazole.
AB - Fixed drug eruption (FDE) is a type of cutaneous drug reaction that occurs at the
same sites upon re-exposure to specific medications. Herein we discuss the case
of a 23-year-old man with a FDE to fluconazole.
PMID- 27617472
TI - Treatment of pediatric pyogenic granuloma in a functionally and cosmetically
sensitive area with the 1064nm ND:Yag laser.
AB - There has been increasing interest in minimally invasive approaches to treat
pyogenic granulomas. We report successful treatment of a pyogenic granuloma in a
pediatric patient on a functionally and cosmetically sensitive area using the
1064nm Nd:YAG laser.
PMID- 27617473
TI - Hereditary angioedema: 44 years of diagnostic delay.
AB - We report a 64-year-old man who suffered from recurrent visible swelling attacks
since the age of 20 as well as episodes with severe upper airway edema, resulting
in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with
hereditary angioedema (HAE) type II. The aims of this report is to emphasize the
importance of awareness concerning HAE, which does not respond to traditional
anti-allergic therapy, and remind physicians to test for functional C1-INH
deficiency.
PMID- 27617475
TI - The impact of immunohistochemistry on the classification of lung tumors.
AB - INTRODUCTION: To highlight the role of immunohistochemistry to lung cancer
classification on the basis of existing guidelines and future perspectives. AREAS
COVERED: Four orienting key-issues were structured according to an extensive
review on the English literature: a) cancer subtyping; b) best biomarkers and
rules to follow; c) negative and positive profiling; d) suggestions towards an
evidence-based proposal for lung cancer subtyping. A sparing material approach
based on a limited number of specific markers is highly desirable. It includes
p40 for squamous cell carcinoma ('no p40, no squamous'), TTF1 for adenocarcinoma,
synaptophysin for neuroendocrine tumors and vimentin for sarcomatoid carcinoma. A
close relationship between genotype and phenotype also supports a diagnostic role
for negative profiles. Expert commentary: Highly specific and sensitive IHC
markers according to positive and negative diagnostic algorithms seem appropriate
for individual patients' lung cancer subtyping.
PMID- 27617474
TI - Higher expression of somatic repair genes in long-lived ant queens than workers.
AB - Understanding why organisms senesce is a fundamental question in biology. One
common explanation is that senescence results from an increase in macromolecular
damage with age. The tremendous variation in lifespan between genetically
identical queen and worker ants, ranging over an order of magnitude, provides a
unique system to study how investment into processes of somatic maintenance and
macromolecular repair influence lifespan. Here we use RNAseq to compare patterns
of expression of genes involved in DNA and protein repair of age-matched queens
and workers. There was no difference between queens and workers in 1-day-old
individuals, but the level of expression of these genes increased with age and
this up-regulation was greater in queens than in workers, resulting in
significantly queen-biased expression in 2-month-old individuals in both legs and
brains. Overall, these differences are consistent with the hypothesis that higher
longevity is associated with increased investment into somatic repair.
PMID- 27617476
TI - Family rituals, financial burden, and mothers' adjustment in pediatric cancer.
AB - The financial burden of childhood cancer may contribute to the distress that
parents experience during and after treatment. Inconsistent relationships between
financial burden and parental psychological distress highlight the need to
identify psychosocial factors that may moderate this relationship. In this study,
we aimed to determine if family ritual meaning moderates the relationship between
financial burden and anxiety and depression symptoms among mothers of children
with cancer. Portuguese mothers of children with cancer on-treatment and off
treatment (N = 244) completed measures of financial burden, anxiety and
depression symptoms, and family ritual meaning. Moderating effects were tested
using hierarchical multiple regression analyses. Family ritual meaning buffered
the effect of financial burden on anxiety, but not on depression symptoms. The
relationship between financial burden and anxiety symptoms was not significant
when mothers endorsed higher levels of family ritual meaning. Although
preliminary, the current findings suggest that high levels of perceived family
ritual meaning may constitute a protective factor against the effect of financial
burden on mothers' anxiety symptoms. Promoting family ritual meaning might be an
effective approach to reducing anxiety symptoms of mothers of children with
cancer in the context of financial burden. (PsycINFO Database Record
PMID- 27617477
TI - Marital, parental, and whole-family predictors of toddlers' emotion regulation:
The role of parental emotional withdrawal.
AB - The present study aims to address how dyadic and triadic family interactions
across the transition to parenthood contribute to the later development of
toddlers' adaptive emotion regulation using structural equation modeling methods.
Specifically, we examined the interrelations of observed marital negative affect
before childbirth, parents' emotional withdrawal during parent-infant
interactions at 8 months, and coparenting conflict at 24 months as predictors of
toddlers' adaptive emotion regulation at 24 months. Data for the present study
were drawn from a longitudinal dataset in which 125 families were observed across
the transition to parenthood. Results suggested that prenatal marital negativity
predicted mothers' and fathers' emotional withdrawal toward their infants at 8
months postbirth as well as coparenting conflict at 24 months postbirth.
Coparenting conflict and father-infant emotional withdrawal were negatively
associated with toddlers' adaptive emotion regulation; however, mother-infant
emotional withdrawal was not related. The implications of our study extend family
systems research to demonstrate how multiple levels of detrimental family
functioning over the first 2 years of parenthood influence toddlers' emotion
regulation and highlight the importance of fathers' emotional involvement with
their infants. (PsycINFO Database Record
PMID- 27617478
TI - A Comparison of Physical and Technical Performance Profiles Between Successful
and Less-Successful Professional Rugby League Teams.
AB - PURPOSE: To examine differences in physical and technical performance profiles
using a large sample of match observations drawn from successful and less
successful professional rugby league teams. METHODS: Match activity profiles were
collected using global positioning satellite (GPS) technology from 29 players
from a successful rugby league team during 24 games and 25 players from a less
successful team during 18 games throughout 2 separate competition seasons.
Technical performance data were obtained from a commercial statistics provider. A
progressive magnitude-based statistical approach was used to compare differences
in physical and technical performance variables between the reference teams.
RESULTS: There were no clear differences in playing time, absolute and relative
total distances, or low-speed running distances between successful and less
successful teams. The successful team possibly to very likely had lower higher
speed running demands and likely had fewer physical collisions than the less
successful team, although they likely to most likely demonstrated more
accelerations and decelerations and likely had higher average metabolic power.
The successful team very likely gained more territory in attack, very likely had
more possessions, and likely committed fewer errors. In contrast, the less
successful team was likely required to attempt more tackles, most likely missed
more tackles, and very likely had a lower effective tackle percentage.
CONCLUSIONS: In the current study, successful match performance was not
contingent on higher match running outputs or more physical collisions; rather,
proficiency in technical performance components better differentiated successful
and less-successful teams.
PMID- 27617480
TI - Photocatalytic Metal-Organic Frameworks for Selective 2,2,2-Trifluoroethylation
of Styrenes.
AB - Synthesis of CF3-containing compounds is of great interest because of their broad
use in the pharmaceutical and agrochemical industries. Herein, selective 2,2,2
trifluoroethylation of styrenes was catalyzed by Zr(IV)-based MOFs bearing
visible-light photocatalysts in the form of Ir(III) polypyridyl complexes. When
compared to the homogeneous Ir(III) catalyst, the MOF-based catalyst suppressed
the dimerization of benzyl radicals, thus enhancing the selectivity of the
desired hydroxytrifluoroethyl compounds.
PMID- 27617479
TI - Pilot study of a brief dialectical behavior therapy skills group for jail
inmates.
AB - Regulating emotions, refraining from impulsive, maladaptive behavior, and
communicating effectively are considered primary treatment needs among jail
inmates. Dialectical behavior therapy (DBT; Linehan, 1993a) skills address these
deficits and have been implemented in long-term correctional settings, but have
yet to be adapted for general population inmates in short-term jail settings.
This study assessed the feasibility and acceptability of a DBT skills group in a
jail setting, as well as its utility in improving coping skills and
emotional/behavioral dysregulation. Male jail inmates participated in an 8-week
DBT skills group and completed pre- and posttest assessments of coping skills,
emotional/behavioral dysregulation, and measures of treatment acceptability. Out
of 27 who started therapy, 16 completed it, primarily due to involuntary
attrition such as transfer to another correctional facility. Although several
logistical issues arose during this pilot study, preliminary results suggest that
a brief DBT skills group is feasible and acceptable in a jail setting, and may
improve coping skills and reduce externalization of blame among general
population jail inmates. This study lays the groundwork for larger, controlled
trials of abbreviated DBT skills groups for general population inmates in short
term jail settings. (PsycINFO Database Record
PMID- 27617481
TI - Facile Synthesis of Platelike Hierarchical Li1.2Mn0.54Ni0.13Co0.13O2 with Exposed
{010} Planes for High-Rate and Long Cycling-Stable Lithium Ion Batteries.
AB - Lithium-rich layered oxides are promising cathode candidates for the production
of high-energy and high-power electronic devices with high specific capacity and
high discharge voltage. However, unstable cycling performance, especially at high
charge-recharge rate, is the most challenge issue which needs to be solved to
foster the diffusion of these materials. In this paper, hierarchical platelike
Li1.2Mn0.54Ni0.13Co0.13O2 cathode materials were synthesized by a facile
solvothermal method followed by calcination. Calcination time was found to be a
key parameter to obtain pure layered oxide phase and tailor its hierarchical
morphology. The Li-rich material consists of primary nanoparticles with exposed
{010} planes assembled to form platelike layers which exhibit low resistance to
Li+ diffusion. In detail, the product by calcination at 900 degrees C for 12 h
exhibits specific capacity of 228, 218, and 204 mA h g-1 at 200, 400, and 1000 mA
g-1, respectively, whereas after 100 cycles at 1000 mA g-1 rate of charge and
recharge the specific capacity was retained by about 91%.
PMID- 27617482
TI - NOESY-Like 2D-IR Spectroscopy Reveals Non-Gaussian Dynamics.
AB - We have identified an unexpected signature of non-Gaussian dynamics in a
conventional 2D IR measurement on a system with rapid intermolecular vibrational
energy transfer. In a ternary mixture of the CO2 reduction photocatalyst,
ReCl(bpy)(CO)3, NaSCN, and THF solvent, preferential association between the
metal carbonyl catalyst and the NaSCN ion pairs facilitates intermolecular energy
transfer on a few picoseconds time scale. Monitoring the cross peak between the
highest frequency metal carbonyl band and the CN bands of NaSCN contact ion
pairs, we find a striking time evolution of the cross-peak position on the
detection axis. This frequency shift, which is due to spectral diffusion
following intermolecular energy transfer, occurs with a time scale that is
distinct from either the donor or acceptor spectral diffusion measured
simultaneously. We argue that the energy transfer, a second-order Forster
process, effectively increases the dimensionality of the 2D-IR spectroscopy and
thus enables sensitivity to non-Gaussian dynamics.
PMID- 27617483
TI - Pomegranate-like N,P-Doped Mo2C@C Nanospheres as Highly Active Electrocatalysts
for Alkaline Hydrogen Evolution.
AB - Well-defined pomegranate-like N,P-doped Mo2C@C nanospheres were prepared by
simply using phosphomolybdic acid (PMo12) to initiate the polymerization of
polypyrrole (PPy) and as a single source for Mo and P to produce N,P-doped Mo2C
nanocrystals. The existence of PMo12 at the molecular scale in the polymer
network allows the formation of pomegranate-like Mo2C@C nanospheres with a porous
carbon shell as peel and Mo2C nanocrystals well-dispersed in the N-doped carbon
matrix as seeds. This nanostructure provides several favorable features for
hydrogen evolution application: (1) the conductive carbon shell and matrix
effectively prevent the aggregation of Mo2C nanocrystals and facilitate electron
transportation; (2) the uniform N,P-doping in the carbon shell/matrix and plenty
of Mo2C nanocrystals provide abundant catalytically highly active sites; and (3)
nanoporous structure allows the effective exposure of active sites and mass
transfer. Moreover, the uniform distribution of P and Mo from the single source
of PMo12 and N from PPy in the polymeric PPy-PMo12 precursor guarantees the
uniform N- and P-co-doping in both the graphitic carbon matrix and Mo2C
nanocrystals, which contributes to the enhancement of electrocatalytic
performance. As a result, the pomegranate-like Mo2C@C nanospheres exhibit
extraordinary electrocatalytic activity for the hydrogen evolution reaction (HER)
in terms of an extremely low overpotential of 47 mV at 10 mA cm(-2) in 1 M KOH,
which is one of the best Mo-based HER catalysts. The strategy for preparing such
nanostructures may open up opportunities for exploring low-cost high-performance
electrocatalysts for various applications.
PMID- 27617484
TI - Periphyton Biofilms Influence Net Methylmercury Production in an Industrially
Contaminated System.
AB - Mercury (Hg) methylation and methylmercury (MMHg) demethylation activity of
periphyton biofilms from the industrially contaminated East Fork Poplar Creek,
Tennessee (EFPC) were measured during 2014-2016 using stable Hg isotopic rate
assays. 201HgII and MM202Hg were added to intact periphyton samples in ambient
streamwater and the formation of MM201Hg and loss of MM202Hg were monitored over
time and used to calculate first-order rate potentials for methylation and
demethylation. The influences of location, temperature/season, light exposure and
biofilm structure on methylation and demethylation potentials were examined.
Between-site differences in net methylation for samples collected from an
upstream versus downstream location were driven by differences in the
demethylation rate potential (kd). In contrast, the within-site temperature
dependent difference in net methylation was driven by changes in the methylation
rate potential (km). Samples incubated in the dark had lower net methylation due
to lower km values than those incubated in the light. Disrupting the biofilm
structure decreased km and resulted in lower net methylation. Overall, the
measured rates resulted in a net excess of MMHg generated which could account for
3.71-7.88 mg d-1 MMHg flux in EFPC and suggests intact, actively
photosynthesizing periphyton biofilms harbor zones of MMHg production.
PMID- 27617485
TI - Exploring the Potential of Cell-Free-DNA Measurements After an Exhaustive Cycle
Ergometer Test as a Marker for Performance-Related Parameters.
AB - PURPOSE: Intensive exercise is known to be accompanied by a rapid release of cell
free DNA (cfDNA). The physiological significance of cfDNA release for performance
diagnostics has not been studied. The authors analyzed the release of cfDNA
during bicycle exercise and its correlation with physiological parameters.
METHODS: Eleven male athletes performed an incremental cycling test. Venous blood
was collected before and immediately after exercise and after 90 min of recovery.
Since the amount of cfDNA is influenced by preanalytical parameters like DNA
extraction and quantification method, the authors applied different measurement
approaches based on quantitative real-time polymerase chain reaction. They
compared a direct measurement procedure not requiring cfDNA extraction for a
short (L1PA290) and a long fragment (L1PA2222) and a procedure for extracted
cfDNA for a short (LTR570) and long fragment (LTR5323) with primers targeting the
repetitive sequences L1PA2 and LTR5 in both assays, respectively. RESULTS: With
the exception of LTR5323, the procedures revealed significant increases of cfDNA
postexercise, whereas the direct approach showed lower interindividual variance
in cfDNA values. When linking cfDNA levels to parameters of exercise performance
the authors observed that, especially, the measurement based on L1PA2222
correlated significantly with exercise markers. These correlations were similar
to the relationship of the performance markers among themselves. CONCLUSIONS:
cfDNA is a possible physiological marker to assess and predict exercise
performance in athletes. In addition, the results indicate that using cfDNA as a
marker in exercise physiology requires careful selection of a suitable
measurement technique, whether it is eluted DNA or directly quantified.
PMID- 27617486
TI - [Viral Infections Among the Nursing Personnel - a Survey].
AB - BACKGROUND AND AIM: Healthcare workers (HCW) are at risk of occupational
infections and can also transmit diseases to patients. The acceptance of measures
to improve safety is linked to knowledge and risk awareness of HCW. The purpose
of our study was to ascertain the knowledge and risk awareness of nursing staff
regarding occupational infections and vaccinations as well as the frequency of
needlestick injuries (NSI) in relation to the level of education. METHODS: In the
context of a conference on nursing, an anonymous questionnaire was distributed to
the participants. RESULTS AND CONCLUSIONS: Nursing staff had insufficient
knowledge of viral occupational infections with regard to the actual hazard. At
the same time, more than 60 % of the respondents rated the probability of
contracting occupational infections as "pretty high" to "very high". In addition,
62.1 % of the study participants also stated that they did not feel sufficiently
trained to care for patients with highly contagious or rare infectious diseases.
Intensified training and awareness programs for nursing personnel are required to
increase the knowledge of occupational infections.